
1: East Mediterr Health J. 2008 Sep-Oct;14(5):1028-35.

Seroprevalence of hepatitis A virus antibodies among a sample of Egyptian
children.

Al-Aziz AM, Awad MA.

Department of Paediatrics, Medical Research Division, National Research Centre,
Cairo, Egypt. dr_amanyaziz@yahoo.com

We determined the seroprevalence of hepatitis A virus antibodies (HAV Ab) among
296 Egyptian children aged 2.5-18 years of different social classes to ascertain 
whether to give HAV vaccine early in life or to leave children to acquire natural
immunity. Overall 61.4% were seropositive for HAV Ab. There was a significant
increase in the seroprevalence of HAV Ab with higher age and lower social class; 
in children aged < 6 years, 72.7% of high and 19.0% of low social class were
seronegative for HAV Ab. A national vaccination programme for HAV is not a
priority. We recommend vaccination against hepatitis A for high social class
children at the preschool period without testing for HAV. Vaccination for middle 
social class children can be done, but only after testing for HAV.

PMID: 19161074 [PubMed - indexed for MEDLINE]

2: Trop Gastroenterol. 2008 Jul-Sep;29(3):160-2.

HAV in Isfahan province: a population-based study.

Ataei B, Javadi AA, Nokhodian Z, Kassaeian N, Shoaei P, Farajzadegan Z, Adibi P.

Infectious Diseases and Tropical Medicine Research Center, Communical Social
Medicine & Internal Medicine and Gastroenterology, Isfahan University of Medical 
Sciences Iran.

INTRODUCTION: Hepatitis A infection is caused by the hepatitis A virus (HAV).
Improved sanitary conditions have resulted in a significant decline in the
incidence of hepatitis A. There is inadequate data about the epidemiology of this
infection in Iran. Therefore, this study was carried out to evaluate the anti-HAV
seroprevalence in Isfahan Province in Iran in 2006. METHODS: In a cross-sectional
study, 816 subjects over 6 years from urban and rural areas of the Isfahan
Province in 2006 using the multi-stage cluster sampling method were selected.
Demographic data and blood samples were collected and anti-HAV antibodies were
measured by ELISA. Chi-square, odds ratio and logistic regression tests were used
for statistical analysis and a p value<0.05 was considered significant. RESULTS: 
The subjects of this study included 428 female and 388 male subjects. The overall
anti-HAV seroprevalence rate was 8.33%. There were statistical differences
between HAV seropositivity in districts of Isfahan province; the highest
seropositivity was seen in Borkhar and Meimeh (28.6%) (p<0.001). There was no
significant difference in HAV seropositivity between the subjects grouped
according to demographic factors. CONCLUSION: HAV seroprevalence in Isfahan
province is not high that can caused by improved sanitary conditions. More
studeis in other parts of Iran are needed to set new strategy for post exposure
prophylaxis and hepatitis A vaccination.

PMID: 19115608 [PubMed - indexed for MEDLINE]

3: Virol J. 2008 Dec 18;5:155.

A simple and rapid Hepatitis A Virus (HAV) titration assay based on antibiotic
resistance of infected cells: evaluation of the HAV neutralization potency of
human immune globulin preparations.

Konduru K, Virata-Theimer ML, Yu MY, Kaplan GG.

Division of Emerging and Transfusion Transmitted Diseases, Center for Biologics
Evaluation and Research, Food and Drug Administration, 29 Lincoln Drive,
Bethesda, Maryland 20892, USA. Krishnamurthy.konduru@fda.hhs.gov

BACKGROUND: Hepatitis A virus (HAV), the causative agent of acute hepatitis in
humans, is an atypical Picornaviridae that grows poorly in cell culture. HAV
titrations are laborious and time-consuming because the virus in general does not
cause cytopathic effect and is detected by immunochemical or molecular probes.
Simple HAV titration assays could be developed using currently available viral
construct containing selectable markers. RESULTS: We developed an antibiotic
resistance titration assay (ARTA) based on the infection of human hepatoma cells 
with a wild type HAV construct containing a blasticidin (Bsd) resistance gene.
Human hepatoma cells infected with the HAV-Bsd construct survived selection with 
2 microg/ml of blasticidin whereas uninfected cells died within a few days. At 8 
days postinfection, the color of the pH indicator phenol red in cell culture
media correlated with the presence of HAV-Bsd-infected blasticidin-resistant
cells: an orange-to-yellow color indicated the presence of growing cells whereas 
a pink-to-purple color indicated that the cells were dead. HAV-Bsd titers were
determined by an endpoint dilution assay based on the color of the cell culture
medium scoring orange-to-yellow wells as positive and pink-to-purple wells as
negative for HAV. As a proof-of-concept, we used the ARTA to evaluate the HAV
neutralization potency of two commercially available human immune globulin (IG)
preparations and a WHO International Standard for anti-HAV. The three IG
preparations contained comparable levels of anti-HAV antibodies that neutralized 
approximately 1.5 log of HAV-Bsd. Similar neutralization results were obtained in
the absence of blasticidin by an endpoint dilution ELISA at 2 weeks
postinfection. CONCLUSION: The ARTA is a simple and rapid method to determine HAV
titers without using HAV-specific probes. We determined the HAV neutralization
potency of human IG preparations in 8 days by ARTA compared to the 14 days
required by the endpoint dilution ELISA. The ARTA reduced the labour, time, and
cost of HAV titrations making it suitable for high throughput screening of sera
and antivirals, determination of anti-HAV antibodies in human immune globulin
preparations, and research applications that involve the routine evaluation of
HAV titers.

Publication Types: 
    Evaluation Studies
    Research Support, U.S. Gov't, P.H.S.

PMID: 19094229 [PubMed - indexed for MEDLINE]

4: Nurs Res. 2009 Jan-Feb;58(1):13-22.

Effects of a nurse-managed program on hepatitis A and B vaccine completion among 
homeless adults.

Nyamathi A, Liu Y, Marfisee M, Shoptaw S, Gregerson P, Saab S, Leake B, Tyler D, 
Gelberg L.

School of Nursing, University of California Los Angeles, Los Angeles, CA
90095-1702, USA. anyamath@sonnet.ucla.edu

BACKGROUND: Hepatitis B virus (HBV) infection constitutes a major health problem 
for homeless persons. Ability to complete an HBV vaccination series is
complicated by the need to prioritize competing needs, such as addiction issues, 
safe places to sleep, and food, over health concerns. OBJECTIVES: The objectives 
of this study were to evaluate the effectiveness of a nurse-case-managed
intervention compared with that of two standard programs on completion of the
combined hepatitis A virus (HAV) and HBV vaccine series among homeless adults and
to assess sociodemographic factors and risk behaviors related to the vaccine
completion. METHODS: A randomized, three-group, prospective, quasi-experimental
design was conducted with 865 homeless adults residing in homeless shelters, drug
rehabilitation sites, and outdoor areas in the Skid Row area of Los Angeles. The 
programs included (a) nurse-case-managed sessions plus targeted hepatitis
education, incentives, and tracking (NCMIT); (b) standard targeted hepatitis
education plus incentives and tracking (SIT); and (c) standard targeted hepatitis
education and incentives only (SI). RESULTS: Sixty-eight percent of the NCMIT
participants completed the three-series vaccine at 6 months, compared with 61% of
SIT participants and 54% of SI participants. NCMIT participants had almost 2
times greater odds of completing vaccination than those of participants in the SI
program. Completers were more likely to be older, to be female, to report fair or
poor health, and not to have participated in a self-help drug treatment program. 
Newly homeless White adults were significantly less likely than were African
Americans to complete the vaccine series. DISCUSSION: The use of vaccination
programs incorporating nurse case management and tracking is critical in
supporting adherence to completion of a 6-month HAV/HBV vaccine. The finding that
White homeless persons were the least likely to complete the vaccine series
suggests that programs tailored to address their unique cultural issues are
needed.

Publication Types: 
    Multicenter Study
    Randomized Controlled Trial
    Research Support, N.I.H., Extramural

PMID: 19092551 [PubMed - indexed for MEDLINE]

5: Am J Trop Med Hyg. 2008 Dec;79(6):980-2.

Short report: elevated levels of alanine aminotransferase and hepatitis A in the 
context of a pediatric malaria vaccine trial in a village in Mali.

Ellis RD, Dicko A, Sagara I, Kamate B, Guindo O, Niambele MB, Sogoba M, Doumbo O.

Malaria Vaccine Development Branch, National Institute of Allergy and Infectious 
Diseases, National Institutes of Health, Bethesda, Maryland 20814, USA.
ellisru@niaid.nih.gov

A Phase 1 study of the apical membrane antigen malaria vaccine AMA1-C1/Alhydrogel
was conducted in 2-3-year-old children in a village in Mali. A high frequency of 
elevated levels of alanine aminotransferase (ALT) caused by hepatitis A was seen,
with 8 of 36 children diagnosed by specific IgM antibody over the course of the
study. Hepatitis A is a common cause of asymptomatic elevations of ALT levels in 
children, particularly in less-developed settings. Investigators should be aware 
of the frequency of hepatitis A in this age group to guard against inadvertently 
facilitating transmission at study facilities and to properly evaluate
symptomatic or asymptomatic elevations of ALT levels.

Publication Types: 
    Clinical Trial, Phase I
    Clinical Trial, Phase II
    Research Support, N.I.H., Intramural

PMID: 19052315 [PubMed - indexed for MEDLINE]

6: Medicine (Baltimore). 2008 Nov;87(6):311-8.

Acute viral infections in patients with systemic lupus erythematosus: description
of 23 cases and review of the literature.

Ramos-Casals M, Cuadrado MJ, Alba P, Sanna G, Brito-Zerón P, Bertolaccini L,
Babini A, Moreno A, D'Cruz D, Khamashta MA.

Laboratory of Autoimmune Diseases Josep Font, Department of Autoimmune Diseases, 
Institut d'Investigacions Biomèdiques August Pi i Sunyer, Hospital Clínic,
Barcelona, Spain. mramos@clinic.ub.es

Few studies have evaluated the impact of viral infections on the daily management
of patients with systemic lupus erythematosus (SLE). We analyzed the etiology and
clinical features of acute viral infections arising in patients with SLE and
their influence on the diagnosis, prognosis, and treatment of SLE. Cases
occurring within the last 5 years were selected from the databases of 3 large
teaching hospitals. Acute viral infections were confirmed by the identification
of specific antiviral IgM antibodies and subsequent seroconversion with detection
of specific IgG antibodies. In autopsy studies, macroscopic findings suggestive
of viral infection were confirmed by direct identification of the virus or
viruses in tissue samples. We performed a MEDLINE search for additional cases
reported between January 1985 and March 2008. We included 88 cases (23 from our
clinics and 65 from the literature review) of acute viral infections in patients 
with SLE. Twenty-five patients were diagnosed with new-onset SLE (fulfillment of 
the 1997 SLE criteria) associated with infection by human parvovirus B19 (n =
15), cytomegalovirus (CMV; n = 6), Epstein-Barr virus (EBV; n = 3), and hepatitis
A virus (n = 1). The remaining 63 cases of acute viral infections arose in
patients already diagnosed with SLE: in 18 patients, symptoms related to
infection mimicked a lupus flare, 36 patients, including 1 patient from the
former group who presented with both conditions, presented organ-specific viral
infections (mainly pneumonitis, colitis, retinitis, and hepatitis), and 10
patients presented a severe, multiorgan process similar to that described in
catastrophic antiphospholipid syndrome-the final diagnosis was hemophagocytic
syndrome in 5 cases and disseminated viral infection in 5. Twelve patients died
due to infection caused by CMV (n = 5), herpes simplex virus (n = 4), EBV (n =
2), and varicella zoster virus (n = 1). Autopsies were performed in 9 patients
and disclosed disseminated herpetic infection in 6 patients (caused by herpes
simplex in 4 cases, varicella in 1, and CMV in 1) and hemophagocytic syndrome in 
3. A higher frequency of renal failure (54% vs. 19%, p = 0.024), antiphospholipid
syndrome (33% vs. 6%, p = 0.023), treatment with cyclophosphamide (82% vs. 37%, p
= 0.008), and multisystemic involvement at presentation (58% vs. 8%, p < 0.001); 
and a lower frequency of antiviral therapy (18% vs. 76%, p < 0.001) were found in
patients who died, compared with survivors. The most common viral infections in
patients with SLE are parvovirus B19 (predominantly mimicking SLE presentation)
and CMV (predominantly presenting in severely immunosuppressed patients). CMV
infection may mimic a lupus flare or present with specific organ involvement such
as gastrointestinal bleeding or pulmonary infiltrates. Other herpesviruses are
common in immunosuppressed SLE patients and may produce a wide range of
manifestations. Physicians should examine the pharynx, eyes, skin, and genitalia 
and should conduct serologic and molecular studies to improve early detection of 
viral infection in patients with SLE.

Publication Types: 
    Review

PMID: 19011502 [PubMed - indexed for MEDLINE]

7: J Infect Dis. 2008 Dec 15;198(12):1776-82.

Persistence of antibody to hepatitis A virus 10 years after vaccination among
children and adults.

Hammitt LL, Bulkow L, Hennessy TW, Zanis C, Snowball M, Williams JL, Bell BP,
McMahon BJ.

Arctic Investigations Program, National Center for Preparedness, Detection and
Control of Infectious Diseases, Centers for Disease Control and Prevention,
Atlanta, Georgia, USA. lhammitt@kilifi.kemri-wellcome.org

BACKGROUND: Hepatitis A vaccination is effective in preventing disease. However, 
the duration of protection after vaccination is unknown. METHODS: We enrolled
persons who responded to a 3-dose primary series of hepatitis A vaccine. For
adults, the first dose was 720 ELISA units (EU) of hepatitis A vaccine,
readministered at 1 and 12 months after the first vaccination (hereafter, "0-1-12
months"); for children aged 3-6 years, the first dose was 360 EU, readministered 
according to 1 of 3 vaccination schedules: 1 and 2 months after the first
vaccination ("0-1-2 months"), 1 and 6 months after the first vaccination ("0-1-6 
months"), or 1 and 12 months after vaccination ("0-1-12 months"). Specimens
collected 1 month and 1-10 years after vaccination were tested for antibody to
hepatitis A virus (anti-HAV) by ELISA. Long-term antibody persistence was
estimated by using the observed rate of decline in geometric mean concentration
(GMC). RESULTS: A total of 144 children and 128 adults were enrolled. Children
vaccinated at 0-1-2 months had a significantly lower GMC of antibody than
children vaccinated at 0-1-12 months, but this difference was statistically
significant only through 4 years of follow-up. All 67 children tested at 10 years
and 25 (96%) of 26 adults tested at 8-9 years had detectable anti-HAV. The
estimated duration of antibody persistence was 21-27 years, depending on the
vaccination schedule. CONCLUSIONS: Anti-HAV persists in adults and children for
more than 10 years after the primary vaccination series. Additional studies are
needed to evaluate the duration of antibody persistence beyond 10 years and to
assess the long-term immunogenicity of the currently recommended 2-dose schedule.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 18976095 [PubMed - indexed for MEDLINE]

8: Scand J Gastroenterol. 2008 Jan;43(1):81-8.

Initial thrombocytopenia as a simple, valuable predictor for clinical
manifestation in acute hepatitis A.

Kim HS, Kim HS, Lee JY, Jang JS, Shin WG, Kim KH, Park JY, Lee JH, Kim HY, Jang
MK.

Department of Internal Medicine, Kangdong Sacred Heart Hospital of Hallym
University Medical Center, Seoul, Republic of Korea.

OBJECTIVE: Although acute hepatitis A (AH-A) is usually self-limited, the
clinical manifestations can vary from mild to severe liver dysfunction. However, 
little is known about the simple, valuable predictors for clinical manifestation 
in AH-A. The objective of this study was to identify the simple clinical
predictors for severe liver dysfunction and its clinical course. MATERIAL AND
METHODS: A total of 162 IgM anti-hepatitis A virus (HAV) positive patients were
enrolled in the study. Severe AH-A was defined as a prothrombin time <40% of
control activity. Various liver-unrelated and liver-related parameters at
presentation were compared separately between the severe AH-A group and the
non-severe group. RESULTS: Mean age (+/-SD) was 27.5 (+/-7.1) years and the
proportion of males was 54% (88/162). Fourteen patients (8.7%) experienced severe
AH-A. Of the liver-unrelated parameters, leukopenia (<4000/microl),
thrombocytopenia (<150,000/microl), and high serum C-reactive protein levels (>8 
mg/l) at presentation were significant predictors for severe AH-A in a univariate
analysis (p<0.05). On multivariate analysis, only thrombocytopenia was an
independent predictor for severe AH-A (odds ratio (OR) 5.562, 95% confidence
interval (CI) 1.153-26.834, p=0.033). Of the liver-related parameters, there were
no independent predictors, as shown by multivariate analysis. The
thrombocytopenia group (33%, 54/162) not only had a longer recovery time (28 days
(range, 14-140) versus 37 days (20-128), p<0.001), but also more frequent
complications (OR 4.632, 95% CI 1.886-11.372, p=0.001) than the
non-thrombocytopenia group. CONCLUSIONS: Initial thrombocytopenia may be a
simple, valuable predictor for severity and clinical course in AH-A.

PMID: 18938776 [PubMed - indexed for MEDLINE]

9: J Viral Hepat. 2008 Oct;15 Suppl 2:69-72.

Differences in hepatitis A seroprevalence among geographical regions in Turkey: a
need for regional vaccination recommendations.

Ceyhan M, Yildirim I, Kurt N, Uysal G, Dikici B, Ecevit C, Aydogan A, Koc A, Yasa
O, Köseoğlu M, Onal K, Hacimustafaoglu M, Celebi S.

Department of Infectious Disease, Faculty of Medicine, Hacettepe University,
Ankara, Turkey. mceyhan@hacettepe.edu.tr

Hepatitis A is a worldwide vaccine-preventable infection. Recommendation of
vaccination depends on the endemicity of the disease. The World Health
Organization recommends universal hepatitis A vaccination in intermediate areas; 
however, there is no need of mass vaccination in high and low endemicity regions.
Therefore, most of the countries are using a vaccination policy according to the 
endemicity characteristic representing the whole of the country. The endemicity
of this infection varies due to sanitary and hygiene conditions and socioeconomic
differences among the countries and in various regions of the same country. A
sample of 1173 persons between the age of 0 and 91 years from nine randomly
selected medical centres from five different geographical centres of Turkey were 
tested for the level of anti-hepatitis A virus (anti-HAV) immunoglobulin-G
antibodies using an enzyme-linked immunosorbent assay. The overall prevalence of 
anti-HAV antibodies was 64.4% (1142/1173). While the rate of sero-positivity was 
over 80% in the 5-9 age group and more than 90% after 14 years of age in
south-eastern and eastern regions, it was lower than 50% at the age of 5-9 years 
in central and western regions and remains under 80% in those areas. We conclude 
that the differences observed in HAV sero-positivity among various geographical
regions in Turkey support a universal HAV immunization policy for children
currently living in regions of intermediate endemicity.

PMID: 18837839 [PubMed - indexed for MEDLINE]

10: J Viral Hepat. 2008 Oct;15 Suppl 2:66-8.

Hepatitis A acute liver failure: follow-up of paediatric patients in southern
Brazil.

Ferreira CT, Vieira SM, Kieling CO, Silveira TR.

Pediatric Liver Transplant Unit, Hospital de Clínicas, Porto Alegre, Brazil.
cristinatarga@terra.com.br

We retrospectively analysed 33 children and adolescents who had been hospitalized
in a liver transplant unit within the previous 10 years for acute liver failure
(ALF). The patients' age varied between 2 months and 15 years of age (median 6.2 
+/- 5.3), and 21 (63%) were male. Thirteen patients (39%) were immunoglobulin-M
anti-hepatitis A virus (HAV) sero-positive. Eleven cases (33%) had an
undetermined aetiology. The 13 children with HAV ALF were between 17 months and
15.6 years of age (median 5.8 +/- 4.6) and eight were male (61.5%). All were on a
list for urgent liver transplant. Of these, five (38%) died while waiting for a
liver. Only one patient recovered spontaneously. Seven patients received a liver 
transplant; three died in the immediate postoperative period and one died 45 days
after transplant. Three children are alive 1, 2 and 5 years after transplant. We 
conclude that HAV was the most frequent cause of ALF, which had high mortality
even when a liver transplant was possible. The results support universal HAV
vaccination in this area.

PMID: 18837838 [PubMed - indexed for MEDLINE]

11: J Viral Hepat. 2008 Oct;15 Suppl 2:62-5.

Long-term trends in hepatitis A incidence following the inclusion of Hepatitis A 
vaccine in the routine nationwide immunization program.

Chodick G, Heymann AD, Ashkenazi S, Kokia E, Shalev V.

Medical Informatics Department, Maccabi Healthcare Services, Tel Aviv, Israel.
Hodik_g@mac.org.il

For many years hepatitis A was one of the most common vaccine preventable
diseases in Israel. In 1999, Israel became the first country to introduce an
inactivated hepatitis A vaccine into its national childhood vaccination program. 
The objectives of the present study were to study trends in disease incidence
after the implementation of the new vaccination policy and to assess vaccination 
coverage among children and adults in Israel. We used the databases of the second
largest HMO in Israel (1.7 million members) to identify patients who had evidence
of hepatitis A in 1998 and 2007 and to collect information on all subjects who
received at least one dose of hepatitis A vaccine during the study period.
Hepatitis A vaccination coverage in children <5 years and 5-14 years of age
increased from 9% and 15% in 1998 to 89% and 68% in 2007, respectively. During
this period the annual incidence of hepatitis A dropped from 142.4 per to 7.6 per
100 000. The most prominent reduction in the age-specific annual incidence rates 
was calculated in children <5 years from 239.4 per 100 000 in 1998 to 2.2 per 100
000 in 2007 and from 310.3 per 100 000 to 3.0 per 100 000 in children aged 5-14
years. In endemic areas, vaccination of infants and children against hepatitis A 
can greatly reduce the total burden of the disease.

PMID: 18837837 [PubMed - indexed for MEDLINE]

12: J Viral Hepat. 2008 Oct;15 Suppl 2:57-61.

Effectiveness of universal hepatitis A immunization of children in Minsk City,
Belarus: four-year follow-up.

Fisenka EG, Germanovich FA, Glinskaya IN, Lyabis OI, Rasuli AM.

Municipal Center of Hygiene and Epidemiology, Minsk, Belarus.
fisenko.l@rambler.ru

Hepatitis A is a reportable disease in Belarus. Universal hepatitis A vaccination
of children aged 6 years in Minsk City began in 2003. This analysis was conducted
to evaluate the short-term impact of the program. Hepatitis A incidence data from
1954 to 2006 was compiled. Vaccination effectiveness was estimated by comparing
the incidence of reported hepatitis A cases after 4 years of immunization (2006) 
with the incidence when the vaccination program started (2003). The vaccines used
were Avaxim 160 or Avaxim 80 (95%) and Havrix 720 (5%). From 2003 through 2006,
hepatitis A incidence in vaccinated children under 14 years was 20-fold lower
than the incidence in unvaccinated children (0.3 cases/10000 vs 5.98/10000; odds 
ratio = 0.05, 95% CI: 0.012-0.202), for a vaccination effectiveness of 95%. The
decreased incidence of hepatitis A in all age groups in 2006 (by 12 times in
preschool children aged 1-5 years, 13 times in children aged 10-14 years and 4-6 
times among adults), including those without high coverage by vaccination,
suggest a herd effect. Routine vaccination also resulted in a shift of the age
pattern of hepatitis A morbidity. The proportion of cases in children under 14
years decreased from 33% to 41% in 2000-2002 to 7% in 2005-2006. We conclude that
introduction of universal hepatitis A vaccination in Minsk resulted in sharply
reduced incidence in both vaccinated and unvaccinated children. Hepatitis A virus
circulation might decrease further by beginning vaccination at a younger age.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18837836 [PubMed - indexed for MEDLINE]

13: J Viral Hepat. 2008 Oct;15 Suppl 2:51-6.

Epidemiology of hepatitis A before and after the introduction of a universal
vaccination programme in Catalonia, Spain.

Domínguez A, Oviedo M, Carmona G, Jansá JM, Borrás E, Salleras L, Plasència A.

Department of Public Health, University of Barcelona, Barcelona, Spain.
angela.dominguez@ub.edu

A universal vaccination program for preadolescents, aged 12 years, with the
hepatitis A + B vaccine was introduced in 1998 in Catalonia (Spain) with the aim 
of protecting the whole population against hepatitis A. The hepatitis A + B
vaccine program replaced the hepatitis B vaccination program for preadolescent
started in 1991. The impact of the hepatitis A + B vaccination program was
studied by assessment of the trend of reported cases of hepatitis A. All cases of
viral hepatitis reported from 1992 to 2006 were included in the study. To
evaluate changes in the epidemiology of hepatitis A, two periods were considered:
a prevaccination period (1992-1998) and a post-vaccination period (2001-2006).
The ratios of the rates were calculated according to age and sex. The comparison 
of rates and proportions was made by calculation of the normal z statistic. A
total of 7536 cases of viral hepatitis were reported, of which 4109 (54.52%) were
hepatitis A. The incidence rate of hepatitis A fell from 5.44 per 100 000
person-years in the prevaccination period to 3.02 in the post-vaccination period.
In males, the rate fell from 6.85 to 3.89 and in females from 4.10 to 2.18. The
male-female ratio of incidence rates was lower in the post-vaccination period. In
males the global decline of incidence rate was 43.26% and in females 46.96%. The 
greatest decline occurred in the 15 to 19 years age group in both sexes (79.1% in
men and 78.34% in women) but declines in the 10-14 years age group were also very
important (69.21% and 67.88%, respectively). In conclusion, hepatitis A incidence
fell in Catalonia in the post-vaccination period in vaccinated adolescents and
also in other unvaccinated groups who have benefited from the indirect effects of
the vaccination program.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18837835 [PubMed - indexed for MEDLINE]

14: J Viral Hepat. 2008 Oct;15 Suppl 2:47-50.

Incidence of Hepatitis A in Argentina after vaccination.

Vacchino MN.

ANLIS_National Institute of Epidemiology Dr. Juan H. Jara, Mar del Plata,
Argentina. vacchinomarta@yahoo.com.ar

In Argentina, the annual incidence rate of reported hepatitis A disease ranged
from 70.5 to 173.8 per 100,000 during 1995-2004. A single dose universal
hepatitis A immunization program aimed at children aged 12 months was started in 
June 2005. The aim was to observe the impact of universal vaccination against
hepatitis A in Argentina. A longitudinal analysis of hepatitis A rates reported
in Argentina since 1995 to the National Notifiable Diseases Surveillance System
(SINAVE). Incidence rates in 2007 were compared with those for the prevaccination
baseline period (1998-2002), overall and by age group and geographical regions.
Overall vaccine coverage in Argentina was 95% in 2006 for the single dose. After 
initiating the program, a sharp decrease in disease rates was observed. The
annual incidence of 10.2 per 100,000 during 2007 represents 88.0% reduction with 
respect to the average incidence rate for the period 1998-2002 (P < 0.001). For
children aged 1 year, an 83.1% reduction in disease was observed in 2007,
compared with the baseline period (P < 0.001). Furthermore, a sharp decline was
also observed in all other age groups 87.1% [2-4 years], 88.7% [5-9 years], 83.6%
[10-14 years], 78.8% [15-49 years], 20.7% [>50 years]. Also important reductions 
were observed in all Argentinian regions. Following the implementation of
universal hepatitis vaccination with a single dose to children at 12 months of
age, hepatitis A rates have declined substantially in Argentina. Monitoring is
needed to verify that vaccination continues to proceed and that low rates are
sustained.

PMID: 18837834 [PubMed - indexed for MEDLINE]

15: J Viral Hepat. 2008 Oct;15 Suppl 2:43-6.

Hepatitis A seroprevalence in children and adults in Kiev City, Ukraine.

Moisseeva AV, Marichev IL, Biloschitchkay NA, Pavlenko KI, Novik LV, Kovinko LV, 
Lyabis OI, Houillon G, Rasuli AM.

Ministry of Health, Kiev, Ukraine.

Ukraine is a zone of moderate hepatitis A endemicity. The changing epidemiology
of the disease because of improved hygiene has shifted the burden of Hepatitis A 
to older age groups where the disease is more severe. Outbreaks have also become 
more common as more of the population has become susceptible to hepatitis A virus
(HAV). To help guide decisions regarding use of hepatitis A vaccine in Ukraine,
we examined the presence of antibody to HAV (anti-HAV) in 1001 persons aged 1 to 
85 years, visiting four municipal healthcare centres in the Ukrainian capital,
Kiev. Overall, the anti-HAV prevalence was 31.9%. Anti-HAV seropositivity
increased with age from 9.2% among children aged 1-5 years to 81.7% among persons
over 50 years, but less than 50% of subjects less than 50 years were HAV
seropositive. No children under 2 years were seropositive. HAV seropositivity was
twice as high in children aged 5-11 years old in the low socio-economic status
group (income less than 150 US$ per family member per month) than in the
middle/high group (11.1% compared to 6.3%) but this disparity disappeared by
adolescence. The prevalence of anti-HAV antibodies in adults was not different
with respect to district of residence within the city. Considering the proportion
of HAV seronegative subjects in all age groups under 50 years, routine
vaccination against HAV of children aged 1-2 years old would appear to be an
effective schedule for hepatitis A prophylaxis in Kiev.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18837833 [PubMed - indexed for MEDLINE]

16: J Viral Hepat. 2008 Oct;15 Suppl 2:38-42.

Modern epidemiology of hepatitis A in the north-western region of the Russian
Federation.

Shliakhtenko L, Plotnikova V, Levakova I, Rubis L, Solovieva E, Mukomolov S.

St. Petersburg Pasteur Institute, St. Petersburg, Russia.

The epidemiological features of hepatitis A virus (HAV) infection were studied in
eleven territories located in the north-western region of the Russian Federation.
The dynamics of HAV infection in Russia and in the region were evaluated during a
17-year period. The age-specific incidence was calculated and 229 305 patients
with acute HAV were identified. The analysed database included HA mixed with
other viral hepatitis infections: it included information about 8 809 HAV
patients. Special attention has been paid to the sero-epidemiological studies
conducted in St Petersburg city. These studies included analysis of age-specific 
incidence in persons 20 years of age and older during 6 years and testing of
blood sera from 1 892 healthy persons for IgG anti-HAV. In general there is a
trend to reduction of HAV incidence in Russia, and in the north-western region,
high indices were registered in some provinces in different years. It was
established three types of age-specific incidence distribution: predominated
incidence in 3-14 years of age (first type), 15-29 years of age (second type) and
uniform distribution in different age groups (third type). It was shown that
decrease of HAV incidence in children and young adults lead to the reduction of
sero-positivity level in the groups 20+ years of age. These characteristics
should be taken in account to define indications for HAV vaccine prophylaxis. HAV
infection in 10-13% of cases mixed with acute or chronic hepatitis B and C in the
last 15 years in St Petersburg. In the middle of 1990s, HAV mostly mixed with
acute viral hepatitis of different aetiology, but in the modern time predominated
type of mixture was presented by HAV and chronic HBV and HCV infections. The
obtained results are useful for viral hepatitis surveillance and control.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18837832 [PubMed - indexed for MEDLINE]

17: J Viral Hepat. 2008 Oct;15 Suppl 2:33-7.

Decline in the risk of hepatitis A virus infection in China, a country with
booming economy and changing lifestyles.

Xu ZY, Wang XY, Liu CQ, Li YT, Zhuang FC.

International Vaccine Institute, Seoul, Korea. xuzhiyi@ivi.int

The objective of the study was to identify the protective factors for the rapid
decline in the risk of hepatitis A virus (HAV) infection in China between 1990
and 2006. Results of serological follow-up and data on annual hepatitis A
incidence were analysed and correlated with economic growth and HAV vaccine
output during the same period. In conclusion, both HAV vaccination and changing
lifestyles associated with the booming economy contributed to the rapid risk
decline. Changing lifestyles played a major role in the decline especially in the
areas with booming economy.

PMID: 18837831 [PubMed - indexed for MEDLINE]

18: J Viral Hepat. 2008 Oct;15 Suppl 2:26-32.

Acute hepatitis A in Italy: incidence, risk factors and preventive measures.

Tosti ME, Spada E, Romanò L, Zanetti A, Mele A; SEIEVA collaborating group.

Collaborators: Marzolini F, Sudano L, Simeoni J, Fischer M, Carraro V, Grandi C, 
Zotti C, Cacello E, Gallone A, Muratori L, Incarbona A, De Luca E, Galati MT,
Signorile L, Alibrandi MP, Bresaz E, Valenza G, Scala AM, Castagno P, Silano V,
Ara G, Paganin, Tacca, Iodice S, Costantino A, Boscardo M, Bertorello A, Barberis
R, Giovanetti F, Marchisio MA, Susani F, D'Angelo M, Fiore M, Prosperi B, Fossati
F, Crippa S, Altomonte G, Zorzut F, Donatoni L, Gallo T, Brianti G, Zamparo E,
Ferro A, Mel R, Vecchia N, Soppelsa M, Lamonato N, Mazzetto M, Russo F, Zolin R, 
Todescato A, Bacciolo N, Rizzato D, Berra L, Pupo A, Nicolardi L, Flora M, Boin
F, De Sisti C, D'Ettore G, Renzulli G, Penon MG, Bellè M, Caffara L, Zivelonghi
G, Soffritti S, Foroni M, Rangoni R, Borrini B, Moschella L, Capra A, Borrini BM,
Zilioli F, Copelli F, Alessandrini A, Morelli A, Camerlengo P, Greci M, Monici L,
Bertazzoni A, Bigliardi M, Santacroce S, Gardenghi L, Casaletti G, Cagarelli R,
Errani F, Lambertini A, Bulgarelli A, Vaccina D, Casolari E, Pezzi A, Todeschini 
R, Andalo' C, Domeniconi G, Calzolari A, Dalle Donne E, Dimaggio ML, Fabbri M,
Savoia N, Taddia F, Cova M, Califano A, Savelli G, Casadio GP, Calderoni B,
Fiumana E, Franceschini M, Pecci A, Mela M, Briata MP, Carloni R, Turello W,
Zoppi G, Torracca P, Ballocchini E, Mazzotta F, Graziani G, Ghiselli G, Di Vito
A, Mazzoli F, Wanderlingh W, Epifani AC, Galletti N, Sbrana F, Battaglini M,
Marinari G, Lombardi A, Genghi L, Lezzi J, Verdelli F, Bindi R, De Sanctis E,
Beltrano A, Conti R, Boncompagni G, Piacentini P, Di Cunto M, Papalini T,
Incandela L, Baretti S, Cecconi R, Staderini C, Ciampi G, Filidei P, Barghini F, 
Carducci E, Pelliccioni AR, Mancini G, Busca L, Peccerillo G, Vanwill J, Agostini
M, Spadoni M, Rossini R, Mengucci R, Agostinelli L, Priori A, Cimini D, Marcolini
P, Achille P, Passatempo R, Migliozzi F, Galassi M, Moretti G, Ghitarrini A,
Ciarrocchi G, Maricotti G, Impulliti S, Picciotti F, Angelini C, De Santis M,
D'Eugenio F, Giaimo M, Tosti A, Pasquale A, Rossi M, Buscosi A, Penza OC, Ciani
C, Santocchia F, Proietti ML, Romizi A, Curtale F, Di Giulio L, Pasqualitto P,
Guzzi A, Allegretti V, Corpolongo D, Porcelli P, Ruta A, Ciarlo G, Dionette P,
Guadagnoli R, Ercole A, Esterini G, Piccoli A, Boggi R, Russo P, Napoli P,
Catacchio MG, Cerocchi C, Linari D, Grillo P, Tedeschi MT, Gnesivo C, Loffredo M,
Labriola V, Pendenza A, Tanzariello E, Santarelli E, Ursino S, Torchia SL,
Santucci L, Alicata F, Viafora S, Cecere R, Pepe F, Patti P, Pesoli M, Aiello C, 
Ruiu M, Beato F, Mathis M, Vilecco P, De Santis D, Aquilani S, Passini A, Micali 
O, Pagano V, Pizzuti R, Minichiello N, Ferrara MA, Citarella A, Fossi E, Bove C, 
D'Argenzio A, Simonetti A, Parlato A, Alfieri R, Peluso F, Palombino R, Giugliano
F, Caiazzo AL, Panico MG, Della Greca V, Trani AM, Barbuti S, Quarto M, Chironna 
M, Matera R, Colamaria R, Madaro A, Scalzo G, Avella F, Bellino E, Masullo M,
Pagano I, Di Martino V, Fedele A, Turco G, Minerba S, Negrone FS, Maldini M, De
Lisa M, Polani E, La Vecchia R, Mauri F, Russo T, Aloia F, Giuffrida S, Peritore 
G, Mangione R, Cuccia M, Rinnone S, Cau S, Saba A, Fracasso D, Frongia O, Marras 
MV, Mereu G.

National Centre of Epidemiology, Surveillance and Health Promotion, Istituto
Superiore di Sanità, Rome, Italy. mariaelena.tosti@iss.it

The incidence of, and risk factors for, acute hepatitis A (AHA) were assessed by 
using data collected from the Italian surveillance system of acute viral
hepatitis (SEIEVA). To this end, a case-control study within a population-based
surveillance for acute viral hepatitis was performed. AHA incidence has been
estimated since 1991; the association with considered risk factors was analysed
from 2001 to 2006 employing cases of acute hepatitis B (AHB) as controls. The
incidence of AHA declined from 4 / 100 000 in 1991 to 1.4/100 000 in 2006, with a
peak during 1996-1998 due to an outbreak in southern Italy. The incidence of AHA 
was highest among persons aged 15-24 years. The case-fatality rate was 2.9 / 10
000. Contact with individuals with AHA [adjusted OR (OR(adj)) = 3.8, 95% CI
2.7-5.5; population-attributable risk (PAR) = 7.5%], travelling to endemic areas 
(OR(adj) = 3.1, 95% CI = 2.6-3.8; PAR = 19.5%), ingestion of raw shellfish
(OR(adj) = 1.8, 95% CI = 1.6-2.1; PAR = 26.6%), and cohabitation with day care
children (OR(adj) = 1.3, 95% CI = 1.01-1.7; PAR = 2.3%) were the main important
risk factors. In 2003, an outbreak, with high case-fatality rate occurred among
intravenous drug users, in a central Italian town. A weak association was found
for male homosexuality when acute hepatitis C cases were employed as controls
(OR(adj) = 1.4 CI, 95% CI = 1.1-1.9). Hepatitis A virus infections are currently 
occurring more frequently in adults, in whom the disease is most severe. In
conclusion, looking at the attributable risks, at present most of the AHA
infections are due to shellfish consumption, travel to endemic areas and contact 
with patients with AHA. Vaccination of individuals at increased risk of
infection, as well as persons with underling liver disease and those at increased
risk of complications, combined with surveillance of shellfish retail outlets are
efficient control measures.

PMID: 18837830 [PubMed - indexed for MEDLINE]

19: J Viral Hepat. 2008 Oct;15 Suppl 2:22-5.

Changing epidemiology of hepatitis A in Brazil: reassessing immunization policy.

Vitral CL, Souto FJ, Gaspar AM.

Departamento de Microbiologia e Parasitologia, Instituto Biomédico, UFF, Niterói,
RJ, Rio de Janeiro, Brazil. clvitral@ioc.fiocruz.br

Recent studies have shown that the prevalence of antibody to hepatitis A virus
(HAV) is decreasing in several Latin American countries. Brazil is a very large
and heterogeneous country, showing striking regional differences. With regard to 
sanitary facilities, 81.7% of the districts in the south-eastern region have
sewage systems, compared with only 5.8% in the northern region. Results of
sero-epidemiological studies and reported hepatitis A outbreaks indicate a change
in the epidemiological pattern of hepatitis A in the country. Individuals,
especially those under the age of 10, are mostly unprotected from HAV infection, 
regardless of their socioeconomic status. During 2000-2005, approximately 14
000-21 000 cases of hepatitis A were reported annually in Brazil, a rate of
7.5-11 cases per 100 000 population. Nationwide, hepatitis A mortality rates
declined progressively from 1980 to 2002. As fatal cases constitute a small, but 
predictable, portion of all acute hepatitis A cases, which are in turn part of
the total number of HAV infections, these data suggest that there has been a
decline in HAV circulation in all Brazilian regions over the last two decades.
Taken together these facts point out that the epidemiological pattern of
hepatitis A is changing in Brazil. Besides improvements in sanitary conditions in
the poorest Brazilian regions, the introduction of hepatitis A vaccination of
young children could be a strategy for controlling HAV infection in the country.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18837829 [PubMed - indexed for MEDLINE]

20: J Viral Hepat. 2008 Oct;15 Suppl 2:16-21.

The need for an evidence-based decision-making process with regard to control of 
hepatitis A.

Gentile A.

Epidemiology Department, Hospital de Niños Ricardo Gutierrez, Buenos Aires,
Argentina. angelagentile@fibertel.com.ar

Universal hepatitis A (HA) vaccination was implemented by the Argentinean
Ministry of Health in June 2005 with a single dose at age 12 months. The decision
was made taking into account the following factors. (1) Disease burden: The
incidence rate for the disease increased from 2003 to 2004; the northern and
western regions of the country were the most affected. Sero-prevalence data for
children 1-15 years old was 54% for the whole country, with differences per
region and age. From May 1982 to September 2002, 210 patients were recruited with
acute hepatic failure; HA was the aetiology in 61% of them. (2)
Cost-effectiveness: Compared with no vaccination, the one-dose schedule would
save US$15.3 millions, with regional variations. (3) Vaccine features:
Immunization with one-dose schedule HA vaccine confers good immunogenicity and
effectiveness. (4) Programmatic feasibility: The National Immunizations Program
has appropriate distribution system for vaccines, with adequate cold chain. (5)
Social acceptance and political compromise: The population largely accepts HA
vaccination and the national authorities should be committed to providing it
regularly. The main global issue is that hepatitis A virus infection remains the 
most commonly reported vaccine-preventable disease in many parts of the world
despite the availability of vaccines.

PMID: 18837828 [PubMed - indexed for MEDLINE]

21: J Viral Hepat. 2008 Oct;15 Suppl 2:1-15.

Has the time come to control hepatitis A globally? Matching prevention to the
changing epidemiology.

Hendrickx G, Van Herck K, Vorsters A, Wiersma S, Shapiro C, Andrus JK, Ropero AM,
Shouval D, Ward W, Van Damme P.

Centre for the Evaluation of Vaccination, Vaccine and Infectious Disease
Institute, University of Antwerp, Faculty of Medicine, Antwerp, Belgium.
Greet.Hendrickx@ua.ac.be

For the first time a global meeting on hepatitis A virus (HAV) infection as
vaccine preventable disease was organized at the end of 2007. More than 200
experts from 46 countries gathered to investigate the changing global HAV
epidemiology reflecting the increasing numbers of persons at risk for severe
clinical disease and mortality from HAV infection. The benefits of childhood and 
adult hepatitis A (HepA) vaccination strategies and the data needed by individual
countries and international health organizations to assess current HepA
prevention strategies were discussed. New approaches in preventing HAV infection 
including universal HepA vaccination were considered. This introductory paper
summarizes the major findings of the meeting and describes the changing
epidemiology of HAV infections and the impact of HepA vaccination strategies in
various countries. Implementation of HepA vaccination strategies should take into
account the level of endemicity, the level of the socio-economic development and 
sanitation, and the risk of outbreaks. A stepwise strategy for introduction of
HepA universal immunisation of children was recommended. This strategy should be 
based on accurate surveillance of cases and qualitative documentation of
outbreaks and their control, secure political support on the basis of
high-quality results, and comprehensive cost-effectiveness studies. The
recognition of the need for increased global attention towards HepA prevention is
an important outcome of this meeting.

Publication Types: 
    Introductory Journal Article

PMID: 18837827 [PubMed - indexed for MEDLINE]

22: Expert Rev Vaccines. 2008 Oct;7(8):1141-50.

Epaxal: a virosomal vaccine to prevent hepatitis A infection.

Bovier PA.

Department of Community and Primary Care Medicine, Geneva University Hospitals,
Switzerland. patrick.bovier@post.harvard.edu

Over the last few decades, different types of inactivated hepatitis A virus (HAV)
vaccines have been developed: several aluminum-adjuvanted vaccines and an
aluminum-free, virosome-formulated vaccine. Both types of vaccines are
whole-virus preparations that are produced by growth of HAV strains in human
diploid cell cultures and are subsequently inactivated with formaldehyde. This
review summarizes all published papers on a virosome-formulated vaccine, Epaxal, 
based on formalin inactivated HAV (strain RG-SB) adsorbed to the surface of
special liposomes (virosomes), that replace aluminum hydroxide as the adjuvant
principle. A single injection of virosomal HAV vaccine is well tolerated and
highly immunogenic, with 88-97% of seroprotection 2 weeks after a first dose. HAV
virosomal vaccine can be administered concomitantly with other vaccines, without 
inducing antigenic competition. Direct comparison with aluminum-adsorbed vaccine 
has shown that the immunogenicity was similar, but fewer local reactions were
reported with Epaxal. Recent studies in children have demonstrated that Epaxal
Junior is also an excellent HAV vaccine for mass vaccination programs.

Publication Types: 
    Review

PMID: 18844588 [PubMed - indexed for MEDLINE]

23: New Microbiol. 2008 Jul;31(3):337-41.

Sewage workers: risk of acquiring enteric virus infections including hepatitis A.

Divizia M, Cencioni B, Palombi L, Panà A.

University of Tor Vergata, Faculty of Medicine, Department of Public Health and
Cellular Biology, Hygiene Institute, Via Montpellier, 1 - 11173 Rome, Italy.
divizia@uniroma2.it

To determine if sewage workers have an increased risk of acquiring viral
infections, 66 workers at a small wastewater plant in north-eastern Italy and 72 
control subjects recruited from blood donors were enrolled in a seroprevalence
study to determine whether sewage workers are at increased risk of acquiring
viral infections. In order to evaluate various risk factors, a questionnaire was 
filled out by each worker whereas seropositivity to Hepatitis A virus,
Coxsackievirus B2 - B3 - B4 - B5, and Echovirus types 1 and 9 was determined in
the laboratory. Anti-HAV antibodies were present in 37.8% of sewage workers and
36.1% of subjects in the control group. The difference was not statistically
significant in the two groups, whereas a significant association was observed
regarding age (P < 0.3). No association was observed with the occupational age,
or with number and duration of contacts per day. The lack of evident occupational
risk for hepatitis A among sewage workers may be explained by the adult age of
the workers (mean age 41.3 years, range 22-58 years), and thus the antibody titre
against different enteroviruses was determined. No statistically significant
differences were evident with the raw values, but considering the 90 degrees
percentile as a dichotomic value for the antibody levels a strong and significant
association was present with Coxsackievirus B3 (O.R. 22.85, C.I. 95% 2.93-178.08)
and Coxsackievirus B2 (O.R. 14.25, C.I. 95% 1.78-113.87). Analysis of the data
confirms a limited risk of acquiring infection and/or disease but also the
evident possibility of silent exposure to the viruses. The shift in HAV
epidemiology and increased morbidity and mortality in adult age suggest that
active immunization against hepatitis A should be considered.

PMID: 18843887 [PubMed - indexed for MEDLINE]

24: Euro Surveill. 2008 Oct 2;13(40). pii: 18995.

Community-wide outbreak of hepatitis A in Latvia, in 2008.

Perevoscikovs J, Lucenko I, Magone S, Brila A, Curikova J.

Sabiedrības Veselības Aģentūra, State Agency Public Health Agency, PHA, Riga,
Latvia. jurijs.perevoscikovs@sva.gov.lv

Since November 2007, an increase in the number of reported hepatitis A cases has 
been observed in Latvia. The aim of this report is to provide an update on the
descriptive epidemiology of hepatitis A in Latvia and suggest some possible
explanations of the recent increase in incidence.

PMID: 18831952 [PubMed - indexed for MEDLINE]

25: Euro Surveill. 2008 Oct 2;13(40). pii: 18997.

Increase in hepatitis A cases in the Czech Republic in 2008--preliminary report.

Fabianova K, Cástková J, Benes C, Kyncl J, Kriz B.

Department of Infectious Diseases Epidemiology, National Institute of Public
Health, Prague, Czech Republic.

The public health protection authorities in the Czech Republic report a rise in
cases of viral hepatitis A (HAV) since the end of May 2008. In total, as many as 
602 HAV cases have been reported in 2008 until the end of calendar week 39 (28
September).

PMID: 18831951 [PubMed - indexed for MEDLINE]

26: Indian J Med Res. 2008 Jul;128(1):32-7.

Investigation of a hepatitis A outbreak in children in an urban slum in Vellore, 
Tamil Nadu, using geographic information systems.

Sowmyanarayanan TV, Mukhopadhya A, Gladstone BP, Sarkar R, Kang G.

Departments of Gastrointestinal Sciences , Christian Medical College Vellore,
Tamil Nadu, India.

BACKGROUND & OBJECTIVE: An outbreak of symptomatic viral hepatitis in children
less than 10 yr of age in Vellore, south India, was investigated and the disease 
pattern studied using serological and epidemiological methods, supplemented by
geographic information systems (GIS) mapping. METHODS: Three cases of hepatitis A
were identified during routine surveillance in a birth cohort House-to-house
visits were undertaken to identify other symptomatic cases and samples collected 
for anti- HAV IgM, ELISA testing. All cases and controls were mapped and
geo-referenced using Arc View GIS 3.3. Spatial clustering was investigated using 
SaTScan 7.0.1 software. Drinking water sources were tested for coliform counts
with the most probable number technique. RESULTS: Of the 965 children surveyed,
26 (2.78%) had jaundice between February to July 2006. From the 26 patients, 11
(42.3%) blood samples were obtained and tested for anti-HAV IgM; 10 (90.9%) were 
found to be positive. Water analysis showed high coliform counts in all samples. 
No spatial clustering of cases could be detected. INTERPRETATION & CONCLUSION:
The outbreak was identified because of the symptomatic presentation of the cases.
Our study highlighted the increasing detection of symptomatic children with
hepatitis A virus infection. Water sources in the area were contaminated and may 
have served as the source of infection. The lack of clustering in GIS analysis
could be due to the common water source.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18820356 [PubMed - indexed for MEDLINE]

27: Vaccine. 2008 Nov 11;26(48):6157-64. Epub 2008 Sep 18.

A statistical model to estimate the impact of a hepatitis A vaccination
programme.

Oviedo M, Pilar Muñoz M, Domínguez A, Borras E, Carmona G.

CIBER Epidemiología y Salud Pública (CIBERESP), Parc de Recerca Biomèdica de
Barcelona, c/Dr. Aiguadé 88, Barcelona, Spain. manel.oviedo@gencat.cat

A program of routine hepatitis A+B vaccination in preadolescents was introduced
in 1998 in Catalonia, a region situated in the northeast of Spain. The objective 
of this study was to quantify the reduction in the incidence of hepatitis A in
order to differentiate the natural reduction of the incidence of hepatitis A from
that produced due to the vaccination programme and to predict the evolution of
the disease in forthcoming years. A generalized linear model (GLM) using negative
binomial regression was used to estimate the incidence rates of hepatitis A in
Catalonia by year, age group and vaccination. Introduction of the vaccine reduced
cases by 5.5 by year (p-value<0.001), but there was a significant interaction
between the year of report and vaccination that smoothed this reduction
(p-value<0.001). The reduction was not equal in all age groups, being greater in 
the 12-18 years age group, which fell from a mean rate of 8.15 per 100,000
person/years in the pre-vaccination period (1992-1998) to 1.4 in the vaccination 
period (1999-2005). The model predicts the evolution accurately for the group of 
vaccinated subjects. Negative binomial regression is more appropriate than
Poisson regression when observed variance exceeds the observed mean
(overdispersed count data), can cause a variable apparently contribute more on
the model of what really makes it.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18804511 [PubMed - indexed for MEDLINE]

28: J Clin Microbiol. 2008 Nov;46(11):3850-2. Epub 2008 Sep 3.

Fatal outcome of hepatitis A virus (HAV) infection in a traveler with incomplete 
HAV vaccination and evidence of Rift Valley Fever virus infection.

Oltmann A, Kämper S, Staeck O, Schmidt-Chanasit J, Günther S, Berg T, Frank C,
Krüger DH, Hofmann J.

Institute of Medical Virology, Berlin Charité University Medicine,
Helmut-Ruska-Haus, Charitéplatz 1, 10117 Berlin, Germany.

Hepatitis A virus (HAV) infection is rarely fatal except in patients with chronic
liver disease. In the case reported here, an elderly women died of HAV infection 
12 years after incomplete HAV vaccination. The possible role of a concordant Rift
Valley fever virus infection acquired in Kenya is discussed.

Publication Types: 
    Case Reports

PMID: 18768649 [PubMed - indexed for MEDLINE]

29: Euro Surveill. 2008 May 29;13(22). pii: 18885.

A food-borne outbreak of hepatitis A virus (HAV) infection in a secondary school 
in Upper Normandy, France, in November 2006.

Schwarz NG, Revillion M, Roque-Afonso AM, Dussaix E, Giraud M, Liberpre C,
Couturier E, Delarocque Astagneau E.

Institut de Veille Sanitaire, Departement des Maladies Infectieuses,
Saint-Maurice, France. n.schwartz@invs.sante.fr

In November 2006, six symptomatic cases of hepatitis A in pupils of a secondary
school in Upper Normandy, France, were reported to the district health service.
This paper describes the outbreak investigation undertaken with the aim to
identify the vehicle and source of infection, implement control measures and
estimate the size of the outbreak. A primary case at the secondary school was
defined as a pupil or a member of the staff with IgM anti-HAV detected in the
serum and with onset of symptoms between 12 and 21 November 2006; a secondary
case was defined as a contact to a primary case and who developed symptoms and
had IgM anti-HAV two to seven weeks later. We performed a case control study of
primary cases, controls being pupils visiting the same school (cases/controls
1:4) and inspected the canteen facilities. All 13 canteen employees were examined
for anti-HAV IgM antibodies. A phylogenetic analysis of HAV of cases was
performed. We identified 10 primary and 5 secondary cases. Among primary cases
90% reported eating liver pate at the canteen compared to 62% among controls (OR 
5.5, 95% CI 0.62-256.9). One liver pate sample contained markers of faecal
contamination. HAV genotypes were of one identical type. All 13 canteen employees
were negative for IgM anti-HAV while four had anti-HAV total antibodies. We found
deficiencies regarding food preparing procedures and insufficient hand washing
facilities. The vehicle of the outbreak was believed to be the liver pate but the
source of HAV could not be identified. Insufficient facilities in the canteen
hindered staff from maintaining a high hygiene standard and were subsequently
improved.

PMID: 18761959 [PubMed - indexed for MEDLINE]

30: J Public Health Manag Pract. 2008 Sep-Oct;14(5):437-41.

Impact of electronic laboratory reporting on hepatitis A surveillance in New York
City.

Moore KM, Reddy V, Kapell D, Balter S.

Department of Ambulatory Care and Prevention, Harvard Medical School and Harvard 
Pilgrim Health Care, Boston, Massachusetts 02215, USA. kristen
moore@harvardpilgrim.org

BACKGROUND: The New York City Department of Health and Mental Hygiene (DOHMH)
coordinates the administration of timely postexposure prophylaxis (PEP) to
contacts of hepatitis A cases, making prompt disease reporting especially
valuable. Electronic laboratory reporting (ELR) has been shown to improve
timeliness of infectious disease reporting, and DOHMH began receiving hepatitis A
reports via ELR in 2002. OBJECTIVES: (1) to quantify the increase in the
proportion of hepatitis A reports received electronically, (2) to assess how
implementation of ELR affected the reporting time of hepatitis A, and (3) to
assess how changes in reporting time impacted the ability to offer timely
prophylaxis to contacts. METHODS: We evaluated the proportion of reports received
via ELR and the annual reporting time of all hepatitis A reports and quantified
the individuals who received PEP from 2000 to 2006. The specific impact of ELR on
laboratory reporting time was assessed for nine laboratories certified as of July
2006. RESULTS: The proportion of hepatitis A reports received via ELR increased
during the study period to 35 percent in 2006. Electronic laboratory reporting
improved the reporting time for most of the laboratories certified to report
electronically, with a median decrease of 17 days. In 2006, DOHMH administered
PEP to 299 individuals; a fourfold increase from 2000. CONCLUSIONS: Electronic
laboratory reporting provides timely disease data to health departments.
Increased utilization of ELR can have a remarkable impact on public health
surveillance and response.

Publication Types: 
    Evaluation Studies

PMID: 18708886 [PubMed - indexed for MEDLINE]

31: Appl Environ Microbiol. 2008 Oct;74(19):6158-60. Epub 2008 Aug 15.

Recovery and sequence analysis of hepatitis a virus from springwater implicated
in an outbreak of acute viral hepatitis.

Tallon LA, Love DC, Moore ZS, Sobsey MD.

North Carolina Center for Public Health Preparedness, University of North
Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
ltallon@hsph.harvard.edu

An outbreak of acute hepatitis A virus in North Carolina was linked to drinking
water from a contaminated shallow spring by phylogenetic analysis of hepatitis A 
virus (HAV) genomic sequences. Detection of HAV and fecal indicators in the water
provided useful and timely information to assist with public health prevention
and control measures.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 18708522 [PubMed - indexed for MEDLINE]

32: Addiction. 2008 Oct;103(10):1687-95. Epub 2008 Aug 14.

Prevalence of hepatitis B, tetanus, hepatitis A, human immunodeficiency virus and
feasibility of vaccine delivery among injecting drug users in Bangkok, Thailand, 
2003-2005.

Sunthornchart S, Linkins RW, Natephisarnwanish V, Levine WC, Maneesinthu K,
Lolekha R, Tappero JW, Trirat N, Muktier S, Chancharastong P, Fox K,
Donchalermpak S, Vitek C, Supawitkul S.

Department of Health Services, Bangkok Metropolitan Administration, Thailand.

OBJECTIVES: To estimate the prevalence of hepatitis B virus (HBV), tetanus,
hepatitis A virus (HAV) and human immunodeficiency virus (HIV) in injecting drug 
users (IDUs), risk factors associated with infection and the feasibility of HBV
vaccine delivery in HBV seronegatives. METHODS: Cross-sectional seroprevalence
survey of 1535 IDUs recruited from 17 Bangkok Metropolitan Administration (BMA)
methadone clinics and HBV vaccination of seronegatives. RESULTS: Prevalence of
antibody to HBV, tetanus, HAV and HIV was 87.8%, 68.1%, 60.2% and 35.9%,
respectively. Prevalence of HBV and HAV increased with increasing age; prevalence
of tetanus decreased with increasing age. Being HIV seropositive was related
inversely to income and being tetanus seronegative. Of the 189 HBV seronegative
IDUs, 81.0% completed the vaccine series. IDUs with HIV had a 6.5-fold odds of
vaccine non-response. CONCLUSIONS: These data underscore the need for, and
feasibility of, vaccine delivery in this population and support targeting efforts
at high-risk age groups.

Publication Types: 
    Multicenter Study
    Research Support, U.S. Gov't, P.H.S.

PMID: 18705685 [PubMed - indexed for MEDLINE]

33: J Occup Environ Med. 2008 Aug;50(8):935-44.

Risk and burden associated with the acquisition of viral hepatitis A and B in the
corporate traveler.

Bunn WB 3rd.

International Truck and Engine Corporation, 4201 Winfield Road, Warrenville, IL
60555, USA. william.bunn@navistar.com

As the number of international business travelers continues to grow, so does the 
list of destinations, many of which are endemic for both hepatitis A and B.
Generally, travelers are unaware of the risks of acquiring viral hepatitis when
traveling; many are unsure of modes of transmission and do not seek pretravel
advice or do not follow the recommendations of travel health professionals.
Infected employees can result in increased health care costs and reduced
productivity in the workplace. Safe and efficacious monovalent vaccines and a
combined hepatitis A and B vaccine are available. Successful corporate health and
immunization programs can prevent hepatitis A and B when employees are abroad on 
business. This article examines the distribution, risks, costs, burden, and
prevention of hepatitis A and B in the international business traveler.

PMID: 18695452 [PubMed - indexed for MEDLINE]

34: Int J Infect Dis. 2009 Jan;13(1):e9-e13. Epub 2008 Aug 3.

Viral hepatitis in a multi-ethnic neighborhood in the Netherlands: results of a
community-based study in a low prevalence country.

Veldhuijzen IK, van Driel HF, Vos D, de Zwart O, van Doornum GJ, de Man RA,
Richardus JH.

Division of Infectious Disease Control, Municipal Public Health Service
Rotterdam-Rijnmond, Rotterdam, the Netherlands. veldhuijzeni@ggd.rotterdam.nl

OBJECTIVES: The prevalence of viral hepatitis varies worldwide. Although the
prevalence of hepatitis A virus (HAV) and hepatitis B virus (HBV) infection is
generally low in Western countries, pockets of higher prevalence may exist in
areas with large immigrant populations. The aim of this study was to obtain
further information on the prevalence of viral hepatitis in a multi-ethnic area
in the Netherlands. METHODS: We conducted a community-based study in a
multi-ethnic neighborhood in the city of Rotterdam, the Netherlands, including
both native Dutch and migrant participants, who were tested for serological
markers of hepatitis A, hepatitis B, and hepatitis C infection. RESULTS: Markers 
for hepatitis A infection were present in 68% of participants. The prevalence of 
hepatitis B core antibodies (anti-HBc), a marker for previous or current
infection, was 20% (58/284). Prevalence of hepatitis A and B varied by age group 
and ethnicity. Two respondents (0.7%) had chronic HBV infection. The prevalence
of hepatitis C was 1.1% (3/271). High levels of isolated anti-HBc were found.
CONCLUSIONS: We found a high prevalence of (previous) viral hepatitis infections.
This confirms previous observations in ethnic subgroups from a national general
population study and illustrates the high burden of viral hepatitis in areas with
large immigrant populations.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18678518 [PubMed - indexed for MEDLINE]

35: J Microbiol Immunol Infect. 2008 Jun;41(3):254-8.

Hepatitis E virus coinfection with hepatotropic viruses in Egyptian children.

Zaki Mel S, Salama OS, Mansour FA, Hossein S.

Department of Clinical Pathology, Faculty of Medicine, Mansoura University,
Egypt. may_s65@hotmail.com

BACKGROUND AND PURPOSE: Major hepatotropic viruses continue to be important
causes of acute viral hepatitis in developing countries. This work was carried
out to detect the seroprevalence of hepatitis E virus (HEV) markers in children
with acute viral hepatitis due to hepatotropic viruses (A, B and C) and non-A,
non-B, non-C acute hepatitis, and to ascertain the influence of HEV
superinfection in individuals infected with hepatitis viruses (A, B and C).
METHODS: We studied prospectively 162 children with sporadic acute hepatitis who 
reported to our hospital. Thirteen healthy controls were also included in the
study. Laboratory investigations were performed, including complete liver
function tests. Complete serological profiles for hepatitis viruses A, B, C and E
were evaluated. RESULTS: HEV immunoglobulin G was detected with highest
percentage among patients with hepatitis B (56.7%), followed by patients with
hepatitis C virus (52.0%), hepatitis A virus (34.1%) and combined hepatitis B and
C viruses (30.0%). The detection rate among patients with non-A, non-B, non-C
hepatitis was 7.1%. HEV immunoglobulin M was found in 4.5% of hepatitis A virus
patients and in 3.3% of hepatitis B patients. The prevalence of HEV
immunoglobulin G and immunoglobulin M correlated with the levels of hepatic
aspartate aminotransferase and alanine aminotransferase in patients with dual
markers of infection with hepatitis E and other viruses compared to patients with
acute hepatitis due to A and C viruses. CONCLUSIONS: HEV serological markers are 
common among children with acute viral hepatitis, especially from hepatitis C and
B viruses. There may be increased sensitivity to HEV coinfection in association
with hepatitis B and C infections. Dual infection with HEV and other hepatotropic
viruses was associated with greater elevation of aspartate and alanine
aminotransferases.

PMID: 18629421 [PubMed - indexed for MEDLINE]

36: Ann Hepatol. 2008 Apr-Jun;7(2):177-9.

Autoimmune hepatitis induced by the prolonged hepatitis A virus infection.

Tabak F, Ozdemir F, Tabak O, Erer B, Tahan V, Ozaras R.

Istanbul University, Cerrahpasa Medical Faculty, Department of Infectious
Diseases.

Hepatitis A virus (HAV) is the most common cause of acute viral hepatitis in the 
world. Rarely, acute infection may persist for a long time. Autoimmune hepatitis 
(AIH) may provide anti-HAV IgM positivity detection for a prolonged time. On the 
other hand, HAV as an infectious agent may also trigger AIH. Here we presented a 
case which seemed like a simple acute viral hepatitis A infection at the
beginning but turned out to be an AIH according to the International Autoimmune
Hepatitis Group's system. A 21-year-old female was diagnosed as symptomatic acute
HAV infection with anti-HAV IgM positivity and elevated aminotransferase levels. 
The other viral serological tests were negative. On the 6th, 12th and 18th months
of the follow up, her anti-HAV IgM positivity still continued and transaminase
levels were also 3 to 7 times high of the upper limit of normal. In addition,
antinuclear antibody was positive. However, on the 19th month anti-HAV IgM could 
be detected as negative. Liver histology was prominent. The patient had a score
of 16 according to the International Autoimmune Hepatitis Group's system. She was
given prednisolone (10 mg/day) and azathioprine (100 mg/day). The
aminotransferase levels were detected within normal ranges at the end of the
first month of therapy. She was in remission during follow up for 6 years. In
conclusion, prolonged HAV infection and AIH may not only trigger each other but
also deteriorate the liver histology. AIH should be investigated in cases of
long-lasting HAV infection in order to begin the treatment earlier. On the other 
hand, AIH patients should also be vaccinated for both HBV and HAV to avoid more
severe diseases.

Publication Types: 
    Case Reports

PMID: 18626439 [PubMed - indexed for MEDLINE]

37: Expert Opin Biol Ther. 2008 Aug;8(8):1177-85.

Recent advances with a virosomal hepatitis A vaccine.

Bovier PA.

Department of Community and Primary Care Medicine, Geneva University Hospitals,
Switzerland. patrick.bovier@post.harvard.edu

BACKGROUND: Epaxal, a virosomal vaccine against hepatitis A virus (HAV)
infection, has been in use for nearly 15 years, especially among at-risk adults. 
Recent studies have shown that it is also a potent vaccine for children.
OBJECTIVE: To summarise recent advances of Epaxal Junior (0.25 ml, paediatric
formulation). METHODS: Published papers reporting results on the virosomal HAV
vaccine were abstracted and reviewed. RESULTS/CONCLUSION: In a comparative
randomised trial, the paediatric dose was found to be highly immunogenic and
non-inferior to the standard dose with respect to seroprotection rates. The
concomitant administration of virosomal HAV vaccine with routine childhood
vaccines was investigated in another trial. The virosomal HAV vaccine did not
interact with the antibody response of routine childhood vaccines which in turn
did not reduce the antibody response to HAV. In countries that recommend
immunisation against hepatitis A, this virosomal vaccine is an excellent
candidate with few side effects at the site of injection.

PMID: 18613769 [PubMed - indexed for MEDLINE]

38: Vaccine. 2008 Aug 18;26(35):4608-16. Epub 2008 Jun 13.

A cost-effectiveness analysis of universal childhood hepatitis A vaccination in
China.

Zhuang GH, Pan XJ, Wang XL.

Department of Epidemiology and Biostatistics, School of Medicine, Xi'an Jiaotong 
University, Xi'an, Shaanxi 710061, China. zhuanggh@mail.xjtu.edu.cn

The socioeconomic improvement has impacted hepatitis A virus (HAV) infection with
a shift from high to intermediate endemicity in many parts of China. The first
China-developed inactivated hepatitis A vaccine, with significantly low price,
was licensed in 2002, prompting us to evaluate whether universal childhood
vaccination is advisable now in China. We considered vaccination scheduled at
ages 12 and 18 months for all healthy children, and assumed that a single cohort 
was enrolled in 2005. A Markov model was used to predict hepatitis A outcomes and
costs. Vaccination was compared with no vaccination, and the cost-effectiveness
of vaccination was evaluated from the health system and the societal
perspectives. The analysis was run separately in five regions (covering all the
31 provinces of Mainland China) defined by anti-HAV prevalence (around 50%,
50-69%, 70-79%, 80-89% and 90%-). The study projects that with the Chinese
low-cost vaccine, vaccination could gain quality adjusted life years (QALYs)
through the whole country and save health system or societal costs in the lowest,
lower, intermediate and higher infection regions. Vaccination should also be
cost-effective in the highest infection region because of low additional costs
per QALY gained. However, vaccination would increase the probability of death due
to hepatitis A in the highest and higher infection regions by 38 and 37 per
million enrolled, respectively, and as vaccine protection loss increases the risk
would also occur in intermediate and lower infection regions. The trend that the 
lower infection level the region has, the more cost-effective vaccination would
be is obvious. Sensitivity analyses prove that our conclusions are robust.
Considering the potential risk of vaccination, as well as unbalanced
socioeconomic developments and significant differences in HAV infection through
the whole country, the study suggests that universal childhood hepatitis A
vaccination should be first administrated in provinces with the lowest infection 
level. With knowledge accumulation and further evaluations, the zone of
immunization would be considered to be expanded gradually from provinces with
lower infection level to those with higher.

PMID: 18597903 [PubMed - indexed for MEDLINE]

39: Cleve Clin J Med. 2008 Jun;75(6):402-3, 409-10.

Update on infectious disease prevention: human papillomavirus, hepatitis A.

Longworth DL.

Department of Medicine, Tufts University School of Medicine, USA.
david.longworth@bhs.org

Key studies on the prevention of human papillomavirus and hepatitis A published
during the past year found that: A quadrivalent vaccine against human
papillomavirus prevents cervical intraepithelial neoplasia, vulvar and vaginal
intraepithelial neoplasia, and anogenital disease in young women. The vaccine is 
likely cost-effective when given to girls, but perhaps not when given to boys.
Although hepatitis A immune globulin is modestly better than hepatitis A vaccine 
for postexposure prophylaxis against hepatitis A, both are highly effective.
Hepatitis A vaccine is now recommended by the Advisory Committee on Immunization 
Practices as the preferred agent in healthy individuals between the ages of 2 and
40.

Publication Types: 
    Review

PMID: 18595548 [PubMed - indexed for MEDLINE]

40: Arch Virol. 2008;153(8):1473-8. Epub 2008 Jul 2.

Analysis of the full-length genome of hepatitis A virus isolated in South
America: heterogeneity and evolutionary constraints.

García-Aguirre L, Cristina J.

Laboratorio de Virología Molecular, Centro de Investigaciones Nucleares, Facultad
de Ciencias, Iguá 4225, Montevideo, Uruguay.

Hepatitis A virus (HAV) is a hepatotropic member of the family Picornaviridae.
Currently, the entire nucleotide sequence is available for only 26 HAV isolates. 
The complete genome sequence of genotype IA HAV from strains isolated in South
America, where genotype IA is the most prevalent genotype, remains unknown. In
this study, the complete nucleotide sequence was determined for a genotype IA HAV
isolate recovered from a Uruguayan patient (HAV5). Phylogenetic analysis
performed using HAV5 and all available full-length IA genotype HAV strains
revealed a high synonymous substitution rate throughout the HAV polyprotein. The 
results of these studies revealed strong selection against amino acid
replacements along the HAV polyprotein and may explain, at least in part, the
presence of a single HAV serotype.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18594941 [PubMed - indexed for MEDLINE]

41: Mem Inst Oswaldo Cruz. 2008 May;103(3):254-8.

Hepatitis A virus subgenotypes dissemination during a community outbreak in a
surrounding region of Rio de Janeiro.

Santos DR, Villar LM, Paula VS, Lima GS, Gaspar AM.

Laboratório de Desenvolvimento Tecnológico, Brasil. santosdl@ioc.fiocruz.br

From December 1999 to December 2001, many cases of hepatitis A were notified in
the county of Belford Roxo involving individuals aged 0 to 79 years. Serum
samples were collected to evaluate the prevalence of anti-hepatitis A virus (HAV)
antibodies, to detect HAV-RNA and to correlate with possible risk factors of HAV 
infection. Serum samples were screened by commercial IgM and total anti-HAV
antibody ELISA and HAV-RNA was isolated and subsequently amplified by reverse
transcription-polymerase chain reaction (RT-PCR) at VP1/2A region, sequenced and 
analyzed. Total anti-HAV prevalence was 87.9% (203/231) and IgM anti-HAV
prevalence was 38.7% (89/231). Multivariate analysis showed that individuals
under 20 years old are risks groups to acquire the infection suggesting that
hygienic habits of young subjects are the principal factor of transmission and so
they could be the target for vaccine programs. HAV-RNA was amplified from 29
(32.5%) IgM anti-HAV positive patients and 26 samples were sequenced and
classified into subgenotypes IB (8 isolates) and IA (18 isolates). Isolates
classified into subgenotype IB were identical representing one distinct strain.
We could observe both subgenotypes circulating during the study which suggests
different sources of infection. Prophylactic measures as vaccination strategies
added to improvements in hygienic and sanitary conditions would be highly
effective to reduction of infection.

PMID: 18592098 [PubMed - indexed for MEDLINE]

42: Expert Rev Vaccines. 2008 Jul;7(5):535-45.

Hepatitis A vaccines.

Nothdurft HD.

Department of Infectious Diseases and Tropical Medicine, University of Munich,
Germany, Leopoldstrasse 5, D-80802 Munich, Germany. nothdurft@lrz.uni-muenchen.de

The global disease burden associated with hepatitis A virus (HAV) is expected to 
increase in the coming years due to a shift in the epidemiological pattern of the
disease. A decrease in the prevalence of natural immunity is leading to an
increased number of adolescents and adults susceptible to a disease that is
associated with greater morbidity, mortality and treatment costs in older-age
groups. Current HAV vaccines have been shown to be safe, highly immunogenic and
confer long-lasting protection against HAV disease. Vaccine-induced antibodies
persist for more than 12 years in vaccinated adults and mathematical modeling
predicts antibody persistence for more than 25 years in over 95% of vaccine
recipients. However, the cost of HAV vaccines has been prohibitive for some
countries. Recent studies in countries with transitioning HAV endemicity indicate
that the cost-benefit ratio of mass vaccination against HAV would be similar to
other routine childhood vaccinations.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 18564009 [PubMed - indexed for MEDLINE]

43: J Infect Dis. 2008 Aug 1;198(3):299-304.

Comment in:
    J Infect Dis. 2008 Aug 1;198(3):297-8.

Excellent response rate to a double dose of the combined hepatitis A and B
vaccine in previous nonresponders to hepatitis B vaccine.

Cardell K, Akerlind B, Sällberg M, Frydén A.

Department of Infectious Diseases, University Hospital, Linköping, Sweden.
Kristina.Cardell@lio.se

BACKGROUND: Hepatitis B vaccine has been shown to be highly efficient in
preventing hepatitis B. However, 5%-10% of individuals fail to develop protective
levels (>or=10 mIU/mL) of antibodies to hepatitis B surface antigen (anti-HBs)
and are considered to be nonresponders. METHODS: A total of 48 nonresponders and 
20 subjects naive to the HBV vaccine received a double dose of combined hepatitis
A and B vaccine (Twinrix) at 0, 1, and 6 months. The levels of anti-HBs and
antibodies to hepatitis A virus (anti-HAV) were determined before vaccination and
1 month after each dose. RESULTS: Among 44 nonresponders, protective anti-HBs
levels were found in 26 (59%) after the first dose and in 42 (95%) after the
third dose. Among the control subjects, the corresponding figures were 10% and
100%, respectively. All subjects seroconverted to anti-HAV. The titers of both
anti-HBs and anti-HAV were lower in the previously nonresponsive subjects (P<
.01). CONCLUSION: Revaccination of nonresponders to the standard hepatitis B
vaccine regimen with a double dose of the combined hepatitis A and B vaccine was 
highly effective. This is most likely explained by the increased dose, a positive
bystander effect conferred by the hepatitis A vaccine, or both.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18544037 [PubMed - indexed for MEDLINE]

44: BMC Infect Dis. 2008 Jun 6;8:78.

Age-specific seroprevalence of hepatitis A in Antananarivo (Madagascar).

Raharimanga V, Carod JF, Ramarokoto CE, Chrétien JB, Rakotomanana F, Talarmin A, 
Richard V.

Unité d'Epidémiologie, Institut Pasteur de Madagascar, BP 1274, Antananarivo 101,
Madagascar. rvmalala@pasteur.mg

BACKGROUND: Hepatitis A virus (HAV) is an enteric, viral, infectious disease
endemic in many developing countries such as Madagascar. Infection is often
subclinical or asymptomatic in children; however, symptomatic acute infections
become more common with increasing age. In some developing countries,
improvements in living conditions have led to changes in the epidemiological
pattern of HAV infection. There are very few reports on the prevalence of HAV in 
Madagascar.This study was to determine the seroprevalence of hepatitis A virus
antibodies in relation to age in the city of Antananarivo, Madagascar. METHODS:
Serum samples collected in 2004 during a cross-sectional survey of individuals
aged between two and 24 years from Antananarivo were tested for anti-HAV antibody
using a commercial enzyme immunoassay kit. Subjects were investigated using a
standardized social and medical history questionnaire. RESULTS: 926 subjects were
enrolled including 406 males and 520 females. There were 251 children under 10
years old and 675 subjects between 10 and 24 years old. Of the 926 serum samples 
tested, 854 (92.2%) were positive for anti-HAV antibodies. The number of
seropositive samples was similar for males and females. The overall
seroprevalence was 83.7% (210/251) for children under 10 years old and 95.5%
(644/675) for subjects aged between 10 and 24 years (p < 0.001). CONCLUSION:
Despite improvements in sanitary conditions and hygiene over the last few years, 
the prevalence of HAV in Antananarivo is high. Only children under five years old
remain susceptible to HAV infection. Immunization against HAV is not needed at
the present time in the Madagascan population, but should be recommended for
travellers.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18538023 [PubMed - indexed for MEDLINE]

45: Indian J Pediatr. 2008 May;75(5):509-10. Epub 2008 Jun 8.

Typhoid fever and viral hepatitis.

Mishra D, Chaturvedi D, Mantan M.

Department of Pediatrics, Chacha Nehru Bal Chikitsalaya, Maulana Azad Medical
College, Geeta Colony, Delhi, India. dr_dmishra@rediffmail.com

Feco-oral route is the most common mode of transmission for both enteric fever
and hepatitis A and E, and thus infection by these agents may occur concurrently 
especially in tropical endemic areas like India. In this scenario, there occurs a
diagnostic dilemma with respect to differentiation from 'typhoid hepatitis', the 
hepatic manifestations of typhoid fever. We herein present such a case and
discuss pertinent issues.

Publication Types: 
    Case Reports

PMID: 18537014 [PubMed - indexed for MEDLINE]

46: Rev Panam Salud Publica. 2008 May;23(5):303-12.

Universal vaccination of children against hepatitis A in Chile: a
cost-effectiveness study.

Quezada A, Baron-Papillon F, Coudeville L, Maggi L.

Faculty of Medicine of University of Chile, Santiago, Chile.

OBJECTIVE: To evaluate the healthcare and economic impact of routine hepatitis A 
vaccination of toddlers in Chile. METHODS: We used a dynamic model of hepatitis A
infection to evaluate the impact of a two-dose vaccination program, administered 
at ages 12 and 18 months. The model incorporated the changing epidemiology of
hepatitis A in Chile and the development of vaccine-induced herd immunity. Our
analysis was conducted from the public payer perspective, and an estimation of
the societal perspective was performed. Costs are expressed in 2005 U.S. dollars.
RESULTS: Vaccination of toddlers rapidly reduced the healthcare burden of
hepatitis A. In the base case (95% vaccination coverage, 100-year time horizon,
1% annual decrease in force of infection), the average number of infections fell 
by 76.6% annually, and associated deaths fell by 59.7%. Even at 50% coverage, the
program reduced infection rates substantially. Routine vaccination of toddlers
had economic as well as health benefits, saving $4,984 per life-year gained (base
case scenario). The program became cost saving after 6 years, and its overall
cost-effectiveness per life-year gained was largely unaffected by changes in
disease-related costs, herd immunity, coverage rate, and annual decrease in force
of infection. CONCLUSIONS: Routine vaccination of toddlers will reduce the rates 
of symptomatic hepatitis A and associated mortality. The two-dose schedule
evaluated here will be less expensive than disease-related costs in the absence
of vaccination from the sixth year of its implementation. These findings support 
the establishment of a routine vaccination program for toddlers in Chile.

PMID: 18510790 [PubMed - indexed for MEDLINE]

47: Jpn J Infect Dis. 2008 May;61(3):239-41.

Outbreak of hepatitis A in Korean military personnel.

Lee CS, Lee JH, Kwon KS.

Department of Internal Medicine, Chonbuk National University Medical School,
Jeonju, Republic of Korea.

This report describes a hepatitis A outbreak among Korean military personnel.
Each case of hepatitis A in this outbreak was defined as a person who had
symptoms compatible with acute viral hepatitis A and had positive HAV IgM between
May 2 and August 14, 2007 in Inje district, Gangwon, Korea. We tested 70 cases
with symptoms for HAV IgM, and 67 cases showed positive results. They included 4 
sergeants, 1 officer and 62 privates. A positive result for HAV IgG among
asymptomatic military personnel was seen in 11.8% of cases. This epidemic
occurred after a heavy rainfall in the military compound area where drinking
water was supplied by the stream water. After the outbreak, the supply of
drinking water was switched to a public water system. All of 178 military
personnel who had no HAV IgG were vaccinated on July 26, 2007. The outbreak was
resolved after the control measures were implemented.

PMID: 18503182 [PubMed - indexed for MEDLINE]

48: Rev Inst Med Trop Sao Paulo. 2008 Mar-Apr;50(2):123-7.

Hemophagocytic syndrome associated with hepatitis A: case report and literature
review.

Tuon FF, Gomes VS, Amato VS, Graf ME, Fonseca GH, Lazari C, Nicodemo AC.

Department of Infectious and Parasitic Diseases, University of São Paulo Medical 
School, São Paulo, SP, Brazil.

Virus-Associated Hemophagocytic Syndrome (VAHS) is a severe hematological
disorder related to some viral infections. It is an illness characterized by
persistent fever, pancytopenia, splenomegaly, hyperferritinemia and, the most
important, hemophagocytosis observed in the bone marrow, liver and/or lymph
nodes. VAHS associated with hepatitis A virus infection is rarely described,
despite the high incidence of this viral infection in the population in general. 
There is no consensus in the literature regarding the optimal treatment of VAHS. 
In this article the clinical features, presumed pathogenesis, diagnostic criteria
and treatment of VAHS are discussed, including description of cases of VAHS
related to hepatitis A virus infection found in the medical literature.

Publication Types: 
    Case Reports
    Review

PMID: 18488094 [PubMed - indexed for MEDLINE]

49: Eur J Gastroenterol Hepatol. 2008 Jun;20(6):561-6.

The role of domestic hygiene in inflammatory bowel diseases: hepatitis A and worm
infestations.

Hafner S, Timmer A, Herfarth H, Rogler G, Schölmerich J, Schäffler A, Ehrenstein 
B, Jilg W, Ott C, Strauch UG, Obermeier F.

Department of Internal Medicine I, University of Regensburg, Regensburg, Germany.

BACKGROUND: Environmental factors are likely to be involved in the pathogenesis
of inflammatory bowel disease (IBD), as the incidence of both Crohn's disease
(CD) and ulcerative colitis (UC) increased with improved living standards in
Europe after World War II. On the basis of earlier reports suggesting that
hygienic standards may also play a role in the pathogenesis of IBD, we
investigated the influence of hepatitis A seroprevalence as an indicator for
poorer hygienic conditions and worm infestations in IBD. METHODS: Hepatitis A
seroprevalence was examined in patients with UC and CD. Patients with minor
endocrinological disorders served as controls. All patients were questioned about
immunizations, parasitic infections (worms), contact with animals, living on a
farm, and ever traveling abroad. Patients were excluded for active hepatitis A
immunization or recent passive immunization. Results are presented as
Mantel-Haenszel odds ratios with 95% confidence interval, adjusted for age group.
RESULTS: The sample included 307 patients (73 CD, 48 UC, and 186 controls).
Hepatitis A seroprevalence was strongly associated with age older than 50 years. 
Age adjusted Mantel-Haenszel odds ratios were 0.25 (0.09-0.71) for UC and 0.75
(0.38-1.46) for CD versus controls. For parasitic infections, the odds ratios
were 1.15 (0.52-2.53) for UC and 0.34 (0.13-0.89) for CD. CONCLUSION: We were
able to demonstrate a negative association of hepatitis A infection with UC only.
In contrast, a novel finding was a strong protective effect of worm infestations 
for the occurrence of CD, but not UC.

Publication Types: 
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 18467916 [PubMed - indexed for MEDLINE]

50: World J Gastroenterol. 2008 May 7;14(17):2771-5.

Protective effect of inactivated hepatitis A vaccine against the outbreak of
hepatitis A in an open rural community.

Shen YG, Gu XJ, Zhou JH.

Xiuzhou District Center for Disease Control and Prevention, Jiaxing, Zhejiang
Province, China. jxshenyuegen@126.com

AIM: To evaluate the protective effect of inactivated hepatitis A vaccine
(Healive) against hepatitis A outbreak in an emergency vaccination campaign.
METHODS: During an outbreak of hepatitis A in Honghe Town, Xiuzhou District,
Jiaxing City, Zhejiang Province, two nonrandomized controlled trials were
conducted in September 2006. The first trial was to vaccinate 108 anti-HAV
negative individuals with close contacts of the patients from September with 1
dose of an inactivated hepatitis A vaccine, Healive. The control group comprised 
of 115 individuals with close contacts of the patients before September. The
second trial was to vaccinate 3365 primary and secondary school students who
volunteered to receive a dose of Healive and 2572 students who did not receive
Healive serving as its controls. An epidemiological survey was conducted to
evaluate the protective efficacy of the vaccine. RESULTS: A total of 136
hepatitis A cases were reported during an outbreak that started in June, peaked
in August and September, and ended after December of 2006. After a massive
vaccination of school children in September, the number of cases declined
significantly. No hepatitis A was detected in the 108 vaccinated individuals with
close contacts of patients, whereas 4 cases of hepatitis A were found in the
controls. The infection rate of hepatitis A was not significantly different in
the individuals with close contacts of patients whether or not they received the 
vaccine (P = 0.122). No hepatitis A was detected in the 3365 students who
received the vaccine, four cases of hepatitis A were found in the controls. The
infection rate of students with or without vaccination was significantly
different in the students who received the vaccine (0/3365 vs 4/2572, P = 0.035).
The protective efficacy of the vaccine was 100%. CONCLUSION: Inactivated
hepatitis A vaccine demonstrates a good protective effect against an outbreak of 
hepatitis A.

Publication Types: 
    Controlled Clinical Trial

PMID: 18461664 [PubMed - indexed for MEDLINE]

51: J Med Virol. 2008 Jul;80(7):1181-8.

Outbreaks of hepatitis A in England and Wales associated with two co-circulating 
hepatitis A virus strains.

Ngui SL, Granerod J, Jewes LA, Crowcroft NS, Teo CG; 2002 Hepatitis A Outbreaks
Investigation Network.

Collaborators: Patel BC, Boxall E, Crowley B, Cunningham R, Davies AJ, Fraser M, 
Ghose AR, Gossain S, Hill S, Huber T, Johnson AS, Looker N, Matin N, Meigh RE,
Newton A, Parry JV, Peacock D, Riordan T, Sillis M, Skidmore S, Stockley J,
Taylor CE, Teferi A, Turner A, Tweddell A, Weller T, Westmorland D, Yee L.

Virus Reference Department, Health Protection Agency, London, United Kingdom.
siewlin.ngui@hpa.org.uk

During 2002, an upsurge in frequency of hepatitis A outbreaks among injecting
drug users was observed in England and Wales. As lack of risk factor information 
and the high mobility of the cases made linkage of outbreaks difficult, the
relationship of nucleotide sequences in the VP1/2PA junction of the hepatitis A
virus (HAV) genome amplified from serum of case-patients was investigated. A
total of 204 HAV RNA positive sera obtained from a network of 23 laboratories
were studied. Comparison of the sequences identified two principal strains: ES1
(n=95) belonging to type IB, and ES2 (n=72) to type IIIA. Of the remaining
samples, 15 were type IA, 11 were type IB and 11 were type IIIA. ES1 predominated
in Doncaster and other towns in Trent and northern England, and ES2 in the
Midlands and southern England; the difference in geographical distribution
between these two strains was significant (P<0.0001). In comparison to the
sporadic cases, cases infected by either ES1 or ES2 tended to be younger,
injecting drug users, people in contact with injecting drug users, or those with 
a history of incarceration in prisons or homelessness (P<0.0001). Cases infected 
by ES1 tended to be younger than those by ES2 (P<0.0001). The association of the 
outbreaks to two geographically restricted strains implicates two principal
transmission pathways associated with injecting behavior. Identifying these
routes may be conducive to preventing further outbreaks.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18461630 [PubMed - indexed for MEDLINE]

52: J Med Virol. 2008 Jul;80(7):1171-80.

Efficient neutralizing activity of cocktailed recombinant human antibodies
against hepatitis A virus infection in vitro and in vivo.

Cao J, Meng S, Li C, Ji Y, Meng Q, Zhang Q, Liu F, Li J, Bi S, Li D, Liang M.

State Key Laboratory for Infectious Disease Prevention and Control, National
Institute for Viral Disease Control and Prevention, China CDC, Xuan Wu Qu,
Beijing, China.

Hepatitis A virus (HAV) is the major pathogen responsible for acute infectious
hepatitis A, a disease that is prevalent worldwide. Although HAV immunization
effectively prevents infection, primary immunizations must be administered at
least 2 weeks prior to HAV exposure. In contrast, passive immunization with
pooled human immunoglobulin (Ig) can provide immediate and rapid protection from 
HAV infection. Because the use of human sera-derived Igs carries the risk of
contamination, we sought to develop recombinant HAV-neutralizing human
antibodies. We prepared a combinatorial phage display library of recombinant
human anti-HAV antibodies from RNA extracted from the blood lymphocytes of a
convalescent hepatitis A patient. Two recombinant human IgG antibodies, HAIgG16
and HAIgG78, were screened from the antibody library by their ability to bind
with high affinity to purified, inactivated HAV virions. These antibodies
recognized different epitopes of the HAV virion capsid, and competed with both
patient sera and well-characterized neutralizing mouse monoclonal antibodies. A
cocktailed mixture of HAIgG16 and HAIgG78 at a 3:1 ratio was prepared to compare 
its combined biological activity with that conferred by each antibody
individually. The cocktailed antibodies displayed a stronger neutralizing
activity in vitro than that observed with either HAIgG16 and HAIgG78 alone. To
determine the in vivo neutralizing abilities of these antibodies, rhesus monkeys 
were inoculated with cocktailed antibodies and challenged with HAV. Whereas
control animals developed hepatitis A and seroconverted to the HAV antibody,
animals receiving cocktailed antibodies were protected either from viral
infection or from developing clinical hepatitis. These results demonstrate that
recombinant human antibody preparations could be used to prevent or treat
early-stage HAV infection.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18461629 [PubMed - indexed for MEDLINE]

53: Intervirology. 2008;51(2):70-4. Epub 2008 Apr 22.

Hepatitis a in Korea: epidemiological shift and call for vaccine strategy.

Lee D, Cho YA, Park Y, Hwang JH, Kim JW, Kim NY, Lee DH, Lee W, Jeong SH.

Department of Internal Medicine, Seoul National University Bundang Hospital,
Seongnam-si, Korea.

OBJECTIVE: The number of adult hepatitis A cases has progressively been
increasing during the last several years in Korea. The aim of the present study
was to describe the recent clinical features of hepatitis A and the
seroprevalence of hepatitis A virus (HAV), and to discuss HAV vaccine strategy in
Korea. METHODS: Retrospective analysis of clinical characteristics of hepatitis A
from 109 patients consecutively enrolled at a community hospital between 2003 and
2006 as well as cross-sectional study of seroprevalence of HAV from 307 patients 
of hospital population group during the same period were performed. RESULTS: Most
hepatitis A cases were young adults in their twenties or thirties, and the
severity of the disease was related to the age of patients. The seroprevalence of
HAV was 62%, which was dependent on the age of patients. HAV seroepidemiology in 
Korea is rapidly changing and a growing number of young adults are susceptible to
HAV infection. CONCLUSIONS: The clinical features and the epidemiological shift
of HAV urge Korea, as well as other countries which are experiencing similar
issues, to promote childhood vaccination and consider catch-up vaccination for
adolescents and young adults. Copyright 2008 S. Karger AG, Basel.

PMID: 18434743 [PubMed - indexed for MEDLINE]

54: J Infect Dis. 2008 May 1;197(9):1282-8.

Comment in:
    J Infect Dis. 2008 May 1;197(9):1220-2.

Declining hepatitis A mortality in the United States during the era of hepatitis 
A vaccination.

Vogt TM, Wise ME, Bell BP, Finelli L.

Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta,
GA 30333, USA. tcv3@cdc.gov

BACKGROUND: Since the mid-1990s, hepatitis A vaccine has been recommended for US 
children living in historically high-incidence states and for persons with other 
risk factors or chronic liver disease (CLD). The incidence of hepatitis A has
declined dramatically during the era of vaccination, but trends in mortality are 
largely unknown. METHODS: US death certificates from 1990 to 2004 for which
hepatitis A was listed as the underlying cause of death were analyzed. Average
annual age-adjusted mortality rates during the prevaccine (1990-1995) and
post-vaccination recommendation (2000-2004) periods were compared using a
Mantel-Haenszel test of association. The number of deaths for which CLD was
listed as a contributing cause was determined. RESULTS: Overall, 1436 deaths due 
to hepatitis A occurred, averaging 96 annually (range, 142 in 1995 to 54 in
2003). CLD contributed to nearly half of these deaths. Mortality rates paralleled
incidence rates, beginning to decline in the mid-1990s and achieving low points
in 2003 and 2004. Average rates were 32% lower in the post-vaccination
recommendation period than in the prevaccine period (P < .01). The decline was
more dramatic for states with (45%; P < .001) than without (23%; P = .002)
recommendations. CONCLUSIONS: Hepatitis A mortality rates have declined over the 
past decade. CLD remains an important and preventable contributing cause of death
due to hepatitis A.

PMID: 18422440 [PubMed - indexed for MEDLINE]

55: Pediatr Infect Dis J. 2008 May;27(5):465-8.

Antibody response to hepatitis A immunization among human immunodeficiency
virus-infected children and adolescents.

Siberry GK, Coller RJ, Henkle E, Kiefner C, Joyner M, Rogers J, Chang J, Hutton
N.

Department of Pediatrics, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
gsiberr1@jhmi.edu

Seventy-one of 84 human immunodeficiency virus (HIV)-infected children [84.5%
(95% confidence interval: 75-91.5%)] were hepatitis A virus (HAV) seropositive
after 2 doses of HAV vaccine. Higher CD4% and HIV suppression were significantly 
associated with increased HAV seropositivity rate. In multivariate analysis, CD4 
>or=25% and young age were independent predictors of HAV seropositivity. Of 7
children given a third HAV vaccine dose because of negative HAV antibody after 2 
doses, 2 (29%) became seropositive.

PMID: 18382387 [PubMed - indexed for MEDLINE]

56: N S W Public Health Bull. 2008 Jan-Feb;19(1-2):32-5.

Hepatitis A: who in NSW is most at risk of infection?

Ward K, McAnulty J.

NSW Public Health Officer Training Program, NSW Department of Health.
kward@doh.health.nsw.gov.au

The incidence of hepatitis A in NSW has declined in recent years, but the
relative importance of risk factors remains unclear. METHODS: We analysed case
data from the NSW Notifiable Diseases Database from 1991 to 2006. RESULTS:
Hepatitis A notification rates fell from 18.9 to 1.4 cases per 100 000 between
1991 and 2006. International travel to endemic areas was the likely exposure for 
50 per cent of cases between 2002 and 2006. Rates were five times higher in
travellers born in countries where hepatitis A is endemic compared with those
born in Australia. CONCLUSION: Travellers born in endemic countries should be
carefully assessed for vaccination before departure.

PMID: 18361867 [PubMed - indexed for MEDLINE]

57: J Med Virol. 2008 May;80(5):798-802.

Dual infection with hepatitis A and E viruses in outbreaks and in sporadic
clinical cases: Cuba 1998-2003.

Rodríguez Lay Lde L, Quintana A, Villalba MC, Lemos G, Corredor MB, Moreno AG,
Prieto PA, Guzmán MG, Anderson D.

Institute for Tropical Medicine Pedro Kourí (IPK), Havana, Cuba. licel@ipk.sld.cu

Viral hepatitis ranks as the fifth cause of morbidity for infectious diseases in 
Cuba. Epidemics are observed frequently in the population, the hepatitis A virus 
being the main agent responsible for such epidemics. Previous reports also
confirmed the circulation of the hepatitis E virus. From 1998 to 2003, 258 serum 
samples were collected by the Reference Laboratory on Viral Hepatitis during 33
outbreaks of acute viral hepatitis as well as from 39 sporadic clinical cases.
Sera were tested for anti-HAV and anti-HEV IgM by EIA. Overall of the 33
outbreaks studied sera from 12 (36.4%) were positive for anti-HAV IgM only, from 
7 (21.2%) were positive for anti-HEV IgM only, and from 14 (42.4%) were positive 
for antibodies to both viruses. Individually of the 258 sera collected, 137
(53.1%) were positives for anti-HAV IgM, 20 (7.8%) were positives for anti-HEV
IgM, 33 (12.8%) were positives for both markers and 68 (26.4%) were negative to
both. Of the clinical cases, 4 (10.3%) were positives for anti-HAV IgM, 13
(33.3%) were positives for anti-HEV IgM and 5 (12.8%) were positives for both
markers. Seventeen (43.6%) sera were negatives for all viral hepatitis markers
available (A-E). A high positivity for HEV was found in outbreaks tested with the
kit produced by CIGB. In particular HEV seems to infect individuals of all ages. 
The results demonstrate the co-circulation of and co-infection with two
enterically transmitted viruses; however a higher positivity was observed for
anti-HAV than to anti-HEV (53.1% vs. 7.8%) in outbreaks.

PMID: 18360913 [PubMed - indexed for MEDLINE]

58: J Med Virol. 2008 May;80(5):791-7.

Seroprevalence and risk factors for hepatitis A, B, and C among Roma and non-Roma
children in a deprived area of Athens, Greece.

Michos A, Terzidis A, Kalampoki V, Pantelakis K, Spanos T, Petridou ET.

1st Pediatric Department, Division of Infectious Diseases, University of Athens, 
Athens, Greece.

The prevalence and risk factors of hepatitis A, B, and C (HAV, HBV, and HCV)
markers were compared in non-Roma and Roma children who lived in a deprived
suburb of Athens, Greece. The study included 216 children, 118 Roma and 98
non-Roma of 9 years median age (range 5-15 years). Among Roma children 98.3% had 
detectable antibodies to HAV, compared with 32.7% among non-Romas (P < 0.0001).
Regarding HBV, 22% Roma children were identified with evidence of past infection 
(anti-HBc(+)), among whom five (4% of the total) were chronic carriers
(HBsAg(+)), whereas no past infection was detected among the non-Romas (P <
0.0001). Markers of past HBV vaccination (anti-HBs(+), anti-HBc(-)) were detected
in only 14% Roma but 96% non-Roma children (P-value < 0.0001). There was some
indication for intrafamilial transmission of HAV and HBV in Roma school children.
Unfavorable living conditions, frequent residency change, lack of child insurance
and primary healthcare delivery were significantly associated with seroprevalence
of HBV infection among Romas. No child in either group was found positive for HCV
markers. These findings document high socioeconomic differentials with regards to
preventable communicable diseases, such as HAV and HBV and underline the need for
enhancing health policy action targeting pockets of minority childhood
populations. Whereas, uptake of HBV vaccination is rather optimal in this general
population, the high seroprevalence of HAV among Romas, also calls for
implementing general vaccination for HAV, early in life.

Publication Types: 
    Comparative Study

PMID: 18360892 [PubMed - indexed for MEDLINE]

59: J Med Virol. 2008 May;80(5):785-90.

Acute hepatitis A virus infection in Turkey.

Normann A, Badur S, Onel D, Kilic A, Sidal M, Larouzé B, Massari V, Müller J,
Flehmig B.

University of Tübingen, Children's Hospital, Tübingen, Germany.

Anti-HAV IgM positive serum samples from acute phase hepatitis A patients from
various areas in Turkey were tested for viral RNA by RT-PCR (reverse
transcriptase polymerase chain reaction), using primer pairs from two different
regions of the HAV genome. The PCR products amplified from both genomic regions
underwent phylogenetic analyses. A comparison of the regions showed the same
genotyping results, and the RT-PCR-2 in the 5'NCR demonstrated greater
sensitivity compared to RT-PCR-1 in the VP1-P2A region. The majority of the
isolates belonged to genotype IB and are related closely to each other; however, 
two isolates related even more strongly to the HAV HM175 strain. Two (n = 37)
RT-PCR positive sera were classified under genotype IA. A surprising finding
emerged for the mean levels of serum transaminases AST and ALT: higher levels
were found in patients under 10 years of age compared to older patients. Anti-HAV
IgM levels were determined quantitatively and, in addition, the HAV-RNA genome
equivalents were ascertained by real time RT-PCR. No evidence was found for an
association between viral load and the higher transaminase levels in the younger 
group.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18360891 [PubMed - indexed for MEDLINE]

60: J Med Virol. 2008 May;80(5):777-84.

Genetic analysis of HAV strains isolated from patients with acute hepatitis in
Korea, 2005-2006.

Yun H, Kim S, Lee H, Byun KS, Kwon SY, Yim HJ, Lim YS, Jeong SH, Jee Y.

Division of Enteric and Hepatitis Viruses, Center for Infectious Diseases, Korea 
National Institute of Health, Seoul, Republic of Korea.

Hepatitis A virus (HAV) is a causative agent of acute viral hepatitis, which
represents a significant public health problem. HAV is usually transmitted by
oral-fecal route and prevalent not only in developing countries but also in
developed countries worldwide. To characterize the HAV wild type strains
circulating in Korea, the VP3/VP1 and VP1/P2A junction regions were detected by
RT-PCR from HAV IgM positives during 2005 and 2006. Among 160 HAV IgM positive
sera, 30% (n = 48) were positive for HAV RNA. Additionally, the VP3/VP1 junction 
regions were detected all six stools, which collected from outbreak in Gyeonggi
province. Phylogenetic analysis of the sequences obtained from 54 distinct HAV
isolates revealed that most of the strains (n = 45) belonged to genotype IA and
the others including nine strains belonged to genotype IIIA. Interestingly, a Q
--> S amino acid change was dominantly observed at position 810 of the VP1/P2A
junction region in 14 isolates. The molecular epidemiology of HAV infection in
Korea has changed with the co-circulation of at least two genotypes and 810Q --> 
S amino acid substitutions were found to be prevalent. These results strongly
suggest that various HAV strains, including genotype IIIA, might be imported from
high-endemic countries into Korea.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18360890 [PubMed - indexed for MEDLINE]

61: Ann Trop Med Parasitol. 2008 Apr;102(3):247-57.

Molecular characterisation of the hepatitis A virus circulating in the 2001-2005 
outbreaks in Thailand.

Barameechai K, Sa-Nguanmoo P, Suwannakarn K, Thongmee C, Payungporn S,
Chongsrisawat V, Theamboonlers A, Poovorawan Y.

Department of Pediatrics, Chulalongkorn University, Rama IV Road, Pathumwan,
Bangkok 10330, Thailand.

In a recent study of hepatitis A virus (HAV) in Thailand, viral isolates
recovered during several outbreaks of infection that occurred between 2001 and
2005 were genotyped and subjected to phylogenetic analysis. Anti-HAV IgM was
detected, by ELISA, in many of the 283 serum samples that were collected from the
provinces of Suphanburi, Songkhla, Chiangrai and Lampang: 40 (48.2% of those
investigated), 38 (47.5%), 25 (41.0%) and 32 (54.2%), respectively. The HAV RNA
in the positive samples was reverse transcribed and amplified, using a nested PCR
focussed on the VP1-2A region, before the nucleotides of the VP1-2A region of
each HAV-RNA-positive sample were sequenced. All the isolates investigated
clustered in subgenotype IA and, hence, are closely related to the strains
previously investigated in Thailand. When the genome of one sample from an
outbreak in Lampang (LP014) was fully sequenced, the results of genome comparison
and phylogenetic analysis again indicated subgenotype 1A, which appears to be the
predominant form of HAV circulating throughout Thailand.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18348779 [PubMed - indexed for MEDLINE]

62: East Mediterr Health J. 2007 Nov-Dec;13(6):1256-64.

Seroprevalence of hepatitis A among children of different socioeconomic status in
Cairo.

Salama II, Samy SM, Shaaban FA, Hassanin AI, Abou Ismail LA.

Department of Community Medicine Research, National Research Centre, Cairo,
Egypt.

To determine seroprevalence of anti-hepatitis A virus (HAV) antibodies and
potential risk factors for and age of contracting symptomatic hepatitis A
infection among children of different socioeconomic status (SES) in Cairo, we
carried out a cross-sectional study on 426 children aged 3-18 years from low SES 
areas and 142 from high SES areas. Seroprevalence was significantly higher with
age. Seropositivity to anti-HAV antibodies was significantly higher among
children of low and very low SES, 90%, compared to children of high SES, 50%.
Water supply and sewage disposal were the most significant risk factors for HAV
seropositivity in children of low SES. Children of high SES were more likely to
be vulnerable to infection in adolescence than those of low SES.

Publication Types: 
    Comparative Study

PMID: 18341176 [PubMed - indexed for MEDLINE]

63: Vaccine. 2008 Mar 25;26(14):1737-41. Epub 2008 Feb 14.

Impact and effectiveness of a mass hepatitis A vaccination programme of
preadolescents seven years after introduction.

Domínguez A, Oviedo M, Carmona G, Batalla J, Bruguera M, Salleras L, Plasència A.

Department of Public Health, University of Barcelona, Barcelona, Spain.
angela.dominguez@ub.edu

AIM: To investigate the impact of a mass hepatitis A vaccination programme in
preadolescents seven years after introduction in terms of its effectiveness and
the prevented fraction. SETTING: The age distribution of notified cases and
incidence rates in Catalonia (Spain) in the periods before (1992-1998) and after 
(1999-2005) introduction of the vaccination programme were compared. MAIN
RESULTS: The incidence rates in the whole population were 5.51 per 100,000
person-years in the 1992-1998 period and 2.98 in the 1999-2005 period. The rate
reduction in the 10-19 years age group was 72.43% and was more than 45% in the
5-9 years and 20-29 years age groups. The effectiveness of the vaccination
programme was 99.04 (95% CI: 93.11-99.88) and the prevented fraction in the 12-19
years age group was 90.13% (95% CI: 84.47-90.89). CONCLUSIONS: The universal
vaccination programme of preadolescents has had an important impact on hepatitis 
A in Catalonia, not only in vaccinated cohorts but also in non-vaccinated age
groups due to a herd immunity effect.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18325642 [PubMed - indexed for MEDLINE]

64: Eur J Pediatr. 2008 Dec;167(12):1435-9. Epub 2008 Mar 5.

Etiology of hemolysis in two patients with hepatitis A infection:
glucose-6-phosphate dehydrogenase deficiency or autoimmune hemolytic anemia.

Ozbay Hosnut F, Ozcay F, Selda Bayrakci U, Avci Z, Ozbek N.

Pediatric Gastroenterology, Hepatology and Nutrition, Başkent University Faculty 
of Medicine, Ankara, Turkey. ferdaozbay72@yahoo.com

We report two children with hemolytic anemia during the course of hepatitis A
infection. On admission, the patients had high blood urea nitrogen, creatinine,
and uric acid levels, as well as anemia, leucocytosis, and direct and indirect
hyperbilirubinemia. Both patients had a glucose-6-phosphate dehydrogenase
deficiency (G6PD) and autoimmune antibodies. They were given vitamin K on
admission. Inadvertent administration of vitamin K could have been related to an 
acute reduction in hemoglobin concentration. To prevent renal damage,
plasmapheresis with fresh frozen plasma was done to clear bilirubin and plasma
hemoglobin. The hyperbilirubinemia responded to plasmapheresis. However, acute
tubular necrosis complicated the clinical course in one patient, and several
sessions of hemodialysis were required. In conclusion, intravascular hemolysis
should be considered in patients with hepatitis A infection, marked
hyperbilirubinemia, and anemia. Although hepatitis A vaccination is not yet
recommended for routine administration, high-risk patients, including those with 
a G6PD deficiency, should be vaccinated against hepatitis A.

Publication Types: 
    Case Reports

PMID: 18320220 [PubMed - indexed for MEDLINE]

65: Pediatr Infect Dis J. 2008 Apr;27(4):287-91.

Universal hepatitis A vaccination in the United States: a call for action.

Lieberman JM, Word BM, Jacobs RJ, Dagan R, Marchant CD.

University of California, Irvine School of Medicine, Irvine, CA, USA.
jay.m.lieberman@questdiagnostics.com

Previous hepatitis A recommendations for the United States targeted vaccination
of at-risk individuals and children living in states and communities with
consistently elevated rates of hepatitis A. Recommendations now call for routine 
hepatitis A vaccination of all children in the United States beginning at age 1
year (12-23 months). Currently, vaccination coverage rates for hepatitis A remain
below rates of other routine childhood vaccines. Achieving a national
immunization rate greater than 90% for the recommended 2 doses of hepatitis A
vaccine would lessen disease impact throughout society. Routine childhood
immunization against hepatitis A can be a highly effective strategy to reduce
infection in children and community transmission of the virus, and the
elimination of indigenous transmission of hepatitis A is an attainable goal.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18316993 [PubMed - indexed for MEDLINE]

66: Vaccine. 2008 Mar 20;26(13):1697-707. Epub 2008 Feb 5.

Basic mathematical models for the temporal dynamics of HAV in medium-endemicity
Italian areas.

Ajelli M, Iannelli M, Manfredi P, degli Atti ML.

Fondazione Bruno Kessler, via Sommarive 18, Povo (Trento), Italy. ajelli@fbk.eu

In some Southern Italy areas Hepatitis A still represents a serious public health
issue. In 1996 a big epidemics in Puglia led that region to adopt a mass
vaccination programme. In this paper a basic mathematical model for the temporal 
trends of Hepatitis A Virus (HAV) in Southern Italy is proposed and investigated.
The model includes the main distinctive features of HAV in Southern Italy, i.e.
multiplicity of exposure factors, and periodic forcing caused by yearly patterns 
of seafood consumption. The analysis illustrates the role played by the risk
factors on equilibria, stability, and the period of HAV oscillations, both
natural and in presence of vaccination. The model also fits well temporal trends 
of HAV in Southern Italy, suggesting that it is a good starting point for more
structured modelling.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18314231 [PubMed - indexed for MEDLINE]

67: BMC Infect Dis. 2008 Feb 28;8:23.

The United States and Canada as a coupled epidemiological system: an example from
hepatitis A.

Amariei R, Willms AR, Bauch CT.

Department of Mathematics and Statistics, The University of Guelph, Guelph,
Canada. ramariei@uoguelph.ca

BACKGROUND: Hepatitis A (HA) is a low-incidence, non-endemic disease in Canada
and the United States (US). However, a large difference in HA incidence between
Canada and HA-endemic countries has made travel an important contributor to
hepatitis A prevalence in Canada. There is also a (smaller) incidence
differential between Canada and the US. Although the US has only moderately
higher HA incidence, the volume of travel by Canadians to the US is many times
higher than travel volume to endemic countries. Hence, travel to the US may
constitute a source of low to moderate risk for Canadian travelers. To our
knowledge, travel to the US has never been included as a potential risk factor
for HA infection in Canadian epidemiologic analyses. The objective of this study 
was to use dynamic models to investigate the possible effects on hepatitis A
incidence in Canada due to (1) implementing vaccination in the US, and (2)
varying the volume of travel by Canadians to the US. METHODS: We developed and
analyzed age-structured compartmental models for the transmission and vaccination
of hepatitis A, for both Canada and the US. Models were parameterized using data 
on seroprevalence, case reporting, and travel patterns. The potential effect of
hepatitis A prevalence in the US on hepatitis A prevalence in Canada was captured
through a term representing infection of Canadians due to travel in the US.
RESULTS: The model suggests that approximately 22% of HA cases in Canada in the
mid 1990s may have been attributable to travel to the US. A universal vaccination
programme that attained 70% coverage in young children in the US in the mid 1990s
could have reduced Canadian incidence by 21% within 5 years. CONCLUSION: Since
not all necessary data were available to parameterize the model, the results
should be considered exploratory. However, the analysis shows that, under
plausible assumptions, the US may be more important for determining HA prevalence
in Canada than is currently supposed. As international travel continues to grow, 
making vaccination policies ever more relevant to populations beyond a country's 
borders, such multi-country models will most likely come into wider use as
predictive aids for policy development.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18307785 [PubMed - indexed for MEDLINE]

68: Trop Doct. 2008 Jan;38(1):65-6.

Childhood seroprevalence of hepatitis A in the United Arab Emirates.

Sharar ZA, Rajah J, Parsons H.

Department of Paediatrics, Sheikh Khalifa Medical City, PO Box 51900, Abu Dhabi, 
UAE.

The seroprevalence of hepatitis A in Emirati children less than 12 years was
20.1% (95% CI 16.4-24.6%) in 2004.

PMID: 18302878 [PubMed - indexed for MEDLINE]

69: Eur J Clin Microbiol Infect Dis. 2008 Jul;27(7):579-85. Epub 2008 Feb 26.

Autochthonous hepatitis E in Southwest England: a comparison with hepatitis A.

Dalton HR, Stableforth W, Hazeldine S, Thurairajah P, Ramnarace R, Warshow U,
Ijaz S, Ellis V, Bendall R.

Royal Cornwall Hospital Trust, Truro, Cornwall, UK.
harry.dalton@rcht.cornwall.nhs.uk

The incidence of hepatitis A is falling. In contrast, autochthonous hepatitis E
is an emerging infection in developed countries. The objective of this study was 
to compare both laboratory-confirmed cases of hepatitis A and autochthonous
hepatitis E over a 2-year period in Cornwall and Devon and anti-hepatitis A virus
(HAV) IgG and anti-hepatitis E virus (HEV) IgG seroprevalence in blood donors.
The databases of microbiology laboratories in Cornwall and Devon were searched
for the number of diagnostic HEV and HAV assays performed during 2005-2006 and
the number of confirmed cases of acute hepatitis A and hepatitis E detected.
Patients were followed up until recovery or death. Sera from 500 blood donors
from the regional centre were tested for HEV and HAV IgG. In total, 28 cases of
autochthonous hepatitis E were identified from 838 assays, and 20 cases of
hepatitis A were identified from 4503 assays. Compared to hepatitis A cases,
patients with hepatitis E were older (mean age 61 vs. 45 years, P = 0.003), less 
likely to present in winter (P = 0.028) and had more complications (five vs.
one). The IgG seroprevalence rates in blood donors were 45% for HAV and 16% for
HEV. There was no relationship between HAV and HEV IgG seropositivity.
Autochthonous hepatitis E may be more common than hepatitis A, affects older
patients, is less likely to occur in winter and may be associated with more
complications. Patients with acute hepatitis, whatever their age or travel
history, should be tested for HEV.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 18299907 [PubMed - indexed for MEDLINE]

70: East Mediterr Health J. 2007 Sep-Oct;13(5):1108-13.

Prevalence of hepatitis A IgG in individuals with chronic hepatitis B infection
in Babol.

Roushan MR, Bijani A, Sagheb R, Jazayeri O.

Department of Infectious Diseases, Yahyanejad Hospital, Islamic Republic of Iran.
hagar2q@yahoo.ca

To determine the prevalence of previous hepatitis A virus (HAV) infection in
people chronically infected with hepatitis B virus (HBV), we assessed the
prevalence of anti-HAV IgG in 392 patients. The study was carried out in Babol,
northern Islamic Republic of Iran from September 2004 to March 2005. Prevalence
in those aged 10-19 years was 59.4% and was significantly lower than that in
those aged 20-29 years (89.8%) and those over 29 years (97.5%). There was no
significant difference in prevalence according to sex or place of residence. A
significant proportion of Iranian adolescents and young adults with chronic HBV
infection are at risk of contracting HAV infection.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18290404 [PubMed - indexed for MEDLINE]

71: J Prev Med Hyg. 2007 Sep;48(3):103-8.

Molecular epidemiology and case-control approaches for management of an outbreak 
of hepatitis A in Liguria, Italy.

Ansaldi F, Marensi L, Puppo S, Rosselli R, Turello V, Zoppi G, Carloni R, Oreste 
P, Riente R, Valle L, Orsi A, Sticchi L, Durando P, Icardi G.

Department of Health Sciences, University of Genoa, Italy.
filippo.ansaldi@unige.it

INTRODUCTION AND METHODS: Hepatitis A remains an important public health problem 
in low endemicity areas, because of the social and economic high burden of
cyclical outbreaks. In this study we described an outbreak of HAV infection
occurred in the city of Genoa and in its proximity and the viral circulation in
the post-epidemic period. In order to identify risk factors associated to the
illness and to determine the source of infection and the dynamics of virus
evolution, we conducted an epidemiological and molecular investigation by a
case-control study and by sequence analysis of high variable regions of the
genome. RESULTS: From May to October 2005, 58 HAV hepatitis cases were notified. 
The case-control study showed that beach establishment attending is strongly
associated with HAV hepatitis (OR = 24.5, p-value < 0.01), at multivariate
analysis. The profile of epidemic curve, the clinical onset of primary cases who 
occurred in few weeks and the geographic distribution of cases clearly indicated 
a common exposure to a point source: the outbreak can be probably associated with
a contaminated food product dispensed in the affected area. The outbreak has been
mainly caused by a single variant, confirming the common exposure to a point
source; this variant previously circulated within homosexual man (MSM) network in
Northern Europe. During the outbreak and in the following months, different
variants originating from Southeast Asia, Southern America and Northern Africa,
have co-circulated: all these cases were related to international travel and none
of these had determined secondary cases. DISCUSSION: The epidemiological picture 
of hepatitis A in Liguria is characterized by a wide heterogeneity of circulating
HAV strains. This pattern could be associated with the increase of imported cases
and transmission within network of persons with similar risk factors. Molecular
approach coupled to descriptive and analytical epidemiological studies appeared
un-replaceable tools for management and control of HAV outbreaks, because of
their capacity to recognize infection origin, transmission patterns and dynamics 
of virus evolution.

PMID: 18274347 [PubMed - indexed for MEDLINE]

72: Mil Med. 2007 Dec;172(12):1275-8.

Seroprevalence of hepatitis A in thai army medical cadets and nursing students: a
reflection of regional risk differences.

Samakoses R, Myint KS, Rangsin R, Areekul W, Kerdpanich A, Watanaveeradej V,
Mammen MP Jr.

Department of Pediatrics, RTA Medical Department, Phramongkutklao Hospital,
Rajavithi Bangkok 10400, Thailand.

A cross-sectional study of 432 army college students comprising 278 medical
cadets and 154 nursing students, ages ranging from 15 to 26 years, was conducted 
in 2001 to determine the seroprevalence of hepatitis A virus (HAV) antibody.
Serum specimens were tested for HAV antibody by a commercial enzyme immunoassay
method. Anti-HAV was detected in 14.0%, 17.5%, and 15.3% of medical cadets,
nursing students, and the total cohort, respectively. There was no statistically 
significant difference in seroprevalence between medical cadets and nursing
students. Increasing prevalence of HAV correlated with increasing age.
Significantly higher seroprevalence was detected in students from provinces
outside of Bangkok compared to those who were from Bangkok (18.7% vs. 9.8%). The 
highest HAV seroprevalence was observed in subjects from the northeastern region 
of Thailand, suggesting that this region may be associated with greater risk for 
infection and should be the focus of preventive health strategies.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18274028 [PubMed - indexed for MEDLINE]

73: Indian J Med Microbiol. 2008 Jan-Mar;26(1):87-8.

Pleural effusion: a rare complication of hepatitis A.

Bukulmez A, Koken R, Melek H, Dogru O, Ovali F.

Department of Pediatrics, Faculty of Medicine, Afyon Kocatepe University, 03200
Afyon, Turkey. aysegulbukulmez@yahoo.com

Hepatitis A (HAV) infection, which is the most common form of hepatitis in the
paediatric age group and which sometimes has a fulminant course, is endemic in
Turkey, constituting one of the country's important health problems. Pleural
effusion also represents a rare benign complication of acute HAV infections. We
describe here a case of Hepatitis A who developed pleural effusion.

Publication Types: 
    Case Reports

PMID: 18227611 [PubMed - indexed for MEDLINE]

74: J Pediatr Health Care. 2008 Jan-Feb;22(1):3-11.

Hepatitis A: disease burden and current childhood vaccination strategies in the
United States.

Koslap-Petraco MB, Shub M, Judelsohn R.

Suffolk County Department of Health Services, Hauppauge, NY 11788, USA.
MaryBeth.Petraco@suffolkcountyny.gov

Hepatitis A can be a serious disease and represents a substantial health and
economic burden. In recent years, a decline in the number of cases of hepatitis A
has been observed, which has been attributed in part to the implementation of
vaccination policies in states with high disease incidence. In May 2006, the
Advisory Committee on Immunization Practices published updated recommendations to
include routine hepatitis A vaccination for all children beginning at 12 to 23
months of age. In this review, information on hepatitis A disease burden is
presented with a discussion on the new recommendations and implementation of
hepatitis A vaccination.

Publication Types: 
    Review

PMID: 18174084 [PubMed - indexed for MEDLINE]

75: Med Sci Monit. 2008 Jan;14(1):CR52-56.

Profile of viral hepatitis A, B, and C in a Saudi Arabian hospital.

Al-Tawfiq JA, Anani A.

Internal Medicine Services Division, Dhahran Health Center, Saudi Aramco Medical 
Services Organization, Saudi Aramco, Dhahran, Saudi Arabia.
jaffar.tawfiq@aramco.com

BACKGROUND: The objective of the study was to investigate the pattern and
epidemiology of viral hepatitis among patients of the Saudi Aramco Medical
Services Organization (SAMSO) in the Eastern Province of Saudi Arabia.
MATERIAL/METHODS: A retrospective analysis of the reported cases of viral
hepatitis was conducted from January 2000 to June 2005. RESULTS: A total of 1214 
patients with viral hepatitis were identified during the study period. Of
hepatitis A, B, and C, HBV was the most predominant type of hepatitis, accounting
for 49.3% of the cases, followed by HCV (40.7%) and HAV (10%). Nine (0.7%)
patients had both HBV and HCV. The male-to-female ratio was higher in HBV
(1.8:1), whereas HAV and HCV showed no significant differences. HAV infection
predominates in children (1-20 years), HBV in young adults (31-50 years), and HCV
in older adults (51-70 years). CONCLUSIONS: HBV continues to be the most
predominant type of viral hepatitis and is a disease of adults, whereas HCV is
mainly a disease of older adults. Continued surveillance of hepatitis cases is
needed to further delineate the risk factors and to establish effective
preventive strategies.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18160946 [PubMed - indexed for MEDLINE]

76: J Virol Methods. 2008 Mar;148(1-2):74-80. Epub 2007 Dec 21.

Comparison between serum and saliva for the detection of hepatitis A virus RNA.

Amado LA, Villar LM, de Paula VS, Gaspar AM.

Laboratory of Technological Development, Department of Virology, Oswaldo Cruz
Institute Foundation, Av. Brasil 4365, Rio de Janeiro, RJ 21045-900, Brazil.
l_amado@ioc.fiocruz.br <l_amado@ioc.fiocruz.br>

Due to the ease of collection, oral fluid is being investigated as an alternative
to serum for diagnostic and epidemiological purposes. However, for prospective
studies involving hepatitis A virus (HAV) RNA detection, a standard methodology
must be developed. In the present study, nested RT-PCR and real-time PCR were
optimized and evaluated for HAV detection and quantification, using oral fluid
from healthy volunteers (n=20) and paired serum/oral fluid samples from
individuals involved in a hepatitis A outbreak (n=78). Using nested RT-PCR, HAV
RNA was detected in 50% of oral fluid and in 42% of serum samples from acute
cases, as well as in 12% of all samples from cases without IgM and total
anti-HAV. Using real-time PCR, HAV RNA was detected in 61% of oral fluid and in
71% of serum samples from acute cases, as well as in 17 and 12%, respectively,
from patients without HAV markers. Mean viral loads were 1.7+/-3.24 x
10(3)copies/ml in oral fluid and 2.8+/-6.46 x 10(3)copies/ml in serum. Although
nested RT-PCR and real-time PCR both detected HAV RNA in oral fluid, real-time
PCR was more sensitive. Oral fluid sample testing could be used as a noninvasive 
method of detecting HAV RNA during HAV outbreaks.

Publication Types: 
    Comparative Study
    Evaluation Studies
    Research Support, Non-U.S. Gov't

PMID: 18160140 [PubMed - indexed for MEDLINE]

77: Pediatr Hematol Oncol. 2007 Dec;24(8):587-94.

Comparison of accelerated and rapid schedules for monovalent hepatitis B and
combined hepatitis A/B vaccines in children with cancer.

Köksal Y, Varan A, Aydin GB, Sari N, Yazici N, Yalcin B, Kutluk T, Akyuz C,
Büyükpamukçu M.

Department of Pediatric Oncology, Hacettepe University, Institute of Oncology,
Ankara, Turkey. yavuzkoksal@yahoo.com

The aim of this study was to determine the efficacy of immunization against
hepatitis A and B infections with "rapid" or "accelerated" schedules in children 
with cancer receiving chemotherapy. Fifty-one children were recruited to receive 
either vaccination schedule, in the "rapid vaccination schedule"; hepatitis B
(group I) or combined hepatitis A/B vaccines (group III) were administered at
months 0, 1, 2, and 12; in the "accelerated vaccination schedule," hepatitis B
(group II) or combined hepatitis A/B (group IV) vaccines were administered on
days 0, 7, 21, and 365 intramuscularly. The seroconversion rates at months 1 and 
3 were 35.7 and 57.1% in group I and 25 and 18.8% in group II, respectively.
Group I developed higher seroconversion rates at month 3. In group III the
seroconversion rates for hepatitis B at months 1 and 3 were 54.5 and 60% and in
group IV 50 and 70%, respectively. For hepatitis A, the seroconversion rates at
months 1 and 3 were 81.8 and 90% in group III and 80 and 88.9% in group IV,
respectively. The accelerated vaccination schedule seems to have no advantage in 
children receiving cancer chemotherapy except for high antibody levels at month
1. In conclusion, the accelerated vaccination schedules are not good choices for 
cancer patients. The combined hepatitis A/B vaccine is more effective than
monovalent vaccine in cancer patients, which probably can be explained by an
adjuvant effect of the antigens. The seroconversion of hepatitis A by the
combined hepatitis A/B vaccination is very good in cancer patients.

Publication Types: 
    Randomized Controlled Trial

PMID: 18092249 [PubMed - indexed for MEDLINE]

78: Pharmacoeconomics. 2008;26(1):17-32.

Cost-effectiveness analyses of hepatitis A vaccine: a systematic review to
explore the effect of methodological quality on the economic attractiveness of
vaccination strategies.

Anonychuk AM, Tricco AC, Bauch CT, Pham B, Gilca V, Duval B, John-Baptiste A, Woo
G, Krahn M.

Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada.

Hepatitis A vaccines have been available for more than a decade. Because the
burden of hepatitis A virus has fallen in developed countries, the appropriate
role of vaccination programmes, especially universal vaccination strategies,
remains unclear. Cost-effectiveness analysis is a useful method of relating the
costs of vaccination to its benefits, and may inform policy. This article
systematically reviews the evidence on the cost effectiveness of hepatitis A
vaccination in varying populations, and explores the effects of methodological
quality and key modelling issues on the cost-effectiveness
ratios.Cost-effectiveness/cost-utility studies of hepatitis A vaccine were
identified via a series of literature searches (MEDLINE, EMBASE, HSTAR and SSCI).
Citations and full-text articles were reviewed independently by two reviewers.
Reference searching, author searches and expert consultation ensured literature
saturation. Incremental cost-effectiveness ratios (ICERs) were abstracted for
base-case analyses, converted to $US, year 2005 values, and categorised to
reflect various levels of cost effectiveness. Quality of reporting,
methodological issues and key modelling issues were assessed using frameworks
published in the literature.Thirty-one cost-effectiveness studies (including 12
cost-utility analyses) were included from full-text article review (n = 58) and
citation screening (n = 570). These studies evaluated universal mass vaccination 
(n = 14), targeted vaccination (n = 17) and vaccination of susceptibles (i.e.
individuals initially screened for antibody and, if susceptible, vaccinated) [n =
13]. For universal vaccination, 50% of the ICERs were <$US20 000 per QALY or
life-year gained. Analyses evaluating vaccination in children, particularly in
high incidence areas, produced the most attractive ICERs. For targeted
vaccination, cost effectiveness was highly dependent on the risk of
infection.Incidence, vaccine cost and discount rate were the most influential
parameters in sensitivity analyses. Overall, analyses that evaluated the combined
hepatitis A/hepatitis B vaccine, adjusted incidence for under-reporting, included
societal costs and that came from studies of higher methodological quality tended
to have more attractive cost-effectiveness ratios. Methodological quality varied 
across studies. Major methodological flaws included inappropriate model type,
comparator, incidence estimate and inclusion/exclusion of costs.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 18088156 [PubMed - indexed for MEDLINE]

79: Euro Surveill. 2007 Dec 1;12(12):E5-6.

Exploration of cost effectiveness of active vaccination in the control of a
school outbreak of hepatitis A in a deprived community in the United Kingdom.

Taylor-Robinson DC, Regan M, Crowcroft N, Parry JV, Dardamissis E.

Division of Public Health, University of Liverpool, United Kingdom.
dctr@liv.ac.uk

In January 2006, an outbreak of hepatitis A occurred in a socio-economically
deprived area of Liverpool, in the United Kingdom (UK), where extensive community
outbreaks of hepatitis had previously occurred. A total of nine cases were
confirmed. Five of these were linked within a primary school. The outbreak
initially occurred among a close social contact group, but there was evidence of 
subsequent person-to-person transmission within a local primary school. The
school was attended by 221 pupils (age range 4-12 years) with a total of 37
teaching and other staff (age range 22-71 years). Following local risk
assessment, mass hepatitis A virus (HAV) vaccination was offered to all staff and
pupils, as all were judged to be likely to have been in close contact with the
affected pupils. A total of 188 of 217 eligible children (87%), and 33 of 37
staff (89%) were vaccinated. A salivary seroprevalence survey was conducted at
the same time as vaccination to assess the benefit of this intervention in the
school population. The survey confirmed high levels of susceptibility to
hepatitis A in this setting (97.8%, 95% CI 91.6 to 99.62). The direct costs of
intervention were estimated as euro5,000. The cost effectiveness of intervention 
varies widely (euro60.50 to euro2,099 per case avoided) depending on the expected
attack rate, which is difficult to estimate due to heterogeneity in published
studies.

PMID: 18076861 [PubMed - indexed for MEDLINE]

80: J Viral Hepat. 2007 Dec;14(12):830-4.

Hepatitis A seroprevalence and its relationship with environmental factors in
children of different age groups in Kahramanmaras, Eastern Mediterranean region
of Turkey.

Kaya D, Guler E, Ekerbicer HC, Dilber C, Karabiber H, Guler S, Davutoglu M,
Ciragil P.

Department of Pediatrics, Faculty of Medicine, Kahramanmaras Sutcu Imam
University, Kahramanmaras, Turkey.

Hepatitis A infections are influenced by environmental and socioeconomic factors.
Epidemiologic studies regarding hepatitis A virus (HAV) infection in Turkey have 
not previously examined these factors. We investigated HAV seroprevalence and its
association with sociodemographic factors among children of various ages in the
Eastern Mediterranean region of Turkey. The study included 1142 children (603
male and 539 female) between ages of 6 months and 18 years. Seropositivity in the
whole group was 57.2%. HAV prevalence rates according to age groups were as
follows: 35.5% in 6-23 months group, 19.2% in 2-5 years group, 74.3% in 6-10
years group, 83.0% in 11-14 years group, 92.8% in 15-18 years group. Risk factors
that influenced seropositivity were; dense population, over-crowded families,
excessive number of siblings, low socioeconomic status and low education of the
mother. As HAV seroprevalence in children older than 6 years of age is high, we
recommend hepatitis A vaccination in this region after the first year of life.

PMID: 18070285 [PubMed - indexed for MEDLINE]

81: Vaccine. 2007 Dec 17;25(52):8718-25. Epub 2007 Nov 5.

Prevalence of hepatitis A virus risk factors in a very low endemic country,
Switzerland.

Mohler-Kuo M, Steffen R, Bopp M, Jacobs RJ, Mutsch M.

Division of Epidemiology and Prevention of Non-Communicable Diseases, Institute
of Social and Preventive Medicine, University of Zurich, Hirschengraben 84,
CH-8001 Zurich, Switzerland.

We aimed to estimate the population-based lifetime exposure to guidelines-based
hepatitis A virus (HAV) risk factors in a country model with very low HAV
endemicity. A cross-sectional survey among randomly selected residents of
Switzerland aged 20-60 years was performed assessing the HAV exposure risk
according to the U.S. and the Swiss guidelines. The adjusted prevalence of
lifetime exposure to HAV-associated risk exceeded 80% with travel being the most 
important risk factor. In addition, not only the HAV vaccination coverage was low
but also lack of awareness was widespread. As projections indicate a further
increase in travel volume resulting imported HAV infections with subsequent
transmission among the resident population are a public health concern and a
universal HAV vaccination strategy for HAV should be evaluated.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18061318 [PubMed - indexed for MEDLINE]

82: Indian J Pediatr. 2007 Nov;74(11):1039-40.

Unilateral palatal palsy with viral hepatitis.

Prasad PL, Prasad AN, Patnaik SK.

Department of Pediatrics, Command Hospital, Lucknow, India.

Isolated unilateral palatal (velopalatopharyngeal) palsy is a clinical rarity.
This usually presents in a child as acute onset rhinolalia, unilateral absent
palatal reflex and pharyngeal asymmetry with a benign self-resolving course.
Etiology remains controversial. We report association of this entity in a male
child with viral hepatitis A.

Publication Types: 
    Case Reports

PMID: 18057689 [PubMed - indexed for MEDLINE]

83: J Rheumatol. 2008 Jan;35(1):166-8. Epub 2007 Nov 15.

Hepatitis A-associated macrophage activation syndrome in children with systemic
juvenile idiopathic arthritis: report of 2 cases.

Russo RA, Rosenzweig SD, Katsicas MM.

Servicio de Inmunología y Reumatología, Hospital de Pediatría Prof Dr Juan P
Garrahan, Buenos Aires, Argentina.

OBJECTIVE: We describe two 3-year-old patients with systemic juvenile idiopathic 
arthritis (SJIA) who developed hepatitis A-associated macrophage activation
syndrome (MAS). One patient showed MAS as the presenting manifestation of SJIA,
while MAS complicated SJIA during the second year of the disease course in the
other child. Both girls presented with fever, jaundice, hepatosplenomegaly,
neurological involvement, mucosal hemorrhage, and purpura. Cytopenias,
hypofibrinogenemia, and hemophagocytosis confirmed the diagnosis. After
aggressive treatment with high-dose corticosteroids and immunosuppressants one
patient entered remission while the other one died. Hepatitis A virus may induce 
severe MAS in SJIA.

Publication Types: 
    Case Reports

PMID: 18050365 [PubMed - indexed for MEDLINE]

84: Eur J Gastroenterol Hepatol. 2007 Nov;19(11):923-6.

Anti-hepatitis A virus seroprevalence among patients with chronic viral liver
disease in Korea.

Kim do Y, Ahn SH, Lee HW, Kim SU, Kim JK, Paik YH, Lee KS, Han KH, Chon CY.

Department of Internal Medicine, Institute of Gastroenterology, Liver Cirrhosis
Clinical Research Center, Yonsei University College of Medicine, Seoul, South
Korea.

BACKGROUND/OBJECTIVE: It is generally recommended that patients with chronic
viral hepatitis should be vaccinated against hepatitis A virus (HAV) infection.
We intended to evaluate the prevalence of IgG anti-HAV according to age in
patients chronically infected with hepatitis B virus or hepatitis C virus in
Korea. METHODS: From June to October 2006, 303 patients (226 male, 77 female)
with chronic hepatitis, liver cirrhosis, or hepatocellular carcinoma were
recruited (mean age 50.8+/-14.4 years; range 16-84). The sera were tested for
antibodies to HAV, and overall and age-specific seroprevalence of anti-HAV was
assessed. RESULTS: Hepatitis B virus infection was the etiology of liver diseases
in 267 patients (88.1%), with hepatitis C virus infection in 36 (11.9%). The
distribution of clinical diagnosis was chronic hepatitis in 86 patients (28.4%), 
liver cirrhosis in 36 (11.9%), and hepatocellular carcinoma in 181 (57.9%). The
patients were categorized by decade of age and the distribution was as follows:
nine patients (2.5%) in their teens, 23 (6.2%) in their 20s, 36 (12.4%) in their 
30s, 78 (25.7%) in their 40s, 72 (24.1%) in their 50s, and 85 (29%) >or=61 years.
The overall seroprevalence of anti-HAV was 87.8% (266/303), and no difference was
observed in sex (86.7 vs. 90.9%, P=0.42). The seroprevalence in each age group
was 22.2, 26.1, 72.2, 97.4, 100 and 98.8%, respectively, showing marked increase 
in those over 40 years of age (P<0.001). CONCLUSION: Our study demonstrates that 
most Korean patients over 40 years of age with chronic liver disease have already
been exposed to HAV.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18049159 [PubMed - indexed for MEDLINE]

85: Pediatr Nephrol. 2008 Apr;23(4):667-9. Epub 2007 Nov 27.

Acute renal failure in a 3-year-old child as part of the drug reaction with
eosinophilia and systemic symptoms (DRESS) syndrome following hepatitis A.

Garnier A, El Marabet el H, Kwon T, Peuchmaur M, Mourier O, Baudouin V, Deschênes
G, Loirat C.

Pediatric Nephrology Unit, Assistance Publique-Hôpitaux de Paris, Hôpital Robert 
Debré, Paris, France. arnaud.garnier@rdb.aphp.fr

We report on a 3-year-old Melanesian girl admitted for acute renal failure
following subfulminant hepatitis A virus infection. While the child was slowly
recovering from severe cytolytic hepatitis, she presented 8 weeks of protracted
fever and major eosinophilia (30,000/microl); thereafter, acute renal failure
(serum creatinine 295 micromol/l) occurred. Renal histology displayed diffuse
eosinophilic infiltrate, with severe acute tubulointerstitial lesions associated 
with mild glomerular endocapillary proliferation and eosinophilic infiltrate,
suggesting an immunoallergic mechanism. The child had received cefixime and
cotrimoxazole 3 weeks prior to hospitalisation for the hepatitis A virus
infection. The final diagnosis was of the syndrome drug reaction with
eosinophilia and systemic symptoms or DRESS, induced by cefixime or cotrimoxazole
and possibly triggered by the hepatitis A virus infection.

Publication Types: 
    Case Reports

PMID: 18040726 [PubMed - indexed for MEDLINE]

86: Liver Int. 2008 Jan;28(1):47-53. Epub 2007 Nov 19.

Molecular characterization of hepatitis A virus in children with fulminant
hepatic failure in Argentina.

Munné MS, Vladimirsky S, Moreiro R, Ciocca M, Cuarterolo M, Otegui L, Soto S,
Brajterman L, Castro R, Sasbón J, Gianivelli S, Buamscha D, Quarleri J, González 
JE.

National Reference Laboratory in Viral Hepatitis, National Institute of
Infectious Diseases, Buenos Aires, Argentina. smunne@anlis.gov.ar

BACKGROUND: Hepatitis A infection, a vaccine-preventable disease, is an important
cause of fulminant hepatic failure (FHF) in children in Argentina. Universal
vaccination in 1-year-old children was implemented in June 2005. The limited
studies about the correlation between the characteristics of the hepatitis A
virus (HAV) and FHF have been carried out in adults. METHODS: Samples from 41
children with FHF were studied from September 2003 to January 2006 and HAV RNA
was detected, sequenced and analysed in the 5' non-coding region and VP1/2A
region. RESULTS: Eighteen HAV strains were characterized and found to be
different at the nucleotide level from the self-limited acute infection strains
that have been circulating in Argentina with no temporal or geographical pattern.
They did not form a genetic cluster, but some of them were identical in the
largest fragment characterized and some of them seemed to be more closely related
in time and/or geographically. CONCLUSION: Our results suggest that viral factors
could be involved in the severity of the clinical presentation of HAV infection
in children in Argentina.

Publication Types: 
    Comparative Study

PMID: 18028318 [PubMed - indexed for MEDLINE]

87: J Viral Hepat. 2007 Nov;14 Suppl 1:1-5.

Hepatitis A and B vaccination and public health.

Hollinger FB, Bell B, Levy-Bruhl D, Shouval D, Wiersma S, Van Damme P.

Baylor College of Medicine, Houston, TX 77030, USA. blaineh@bcm.edu

The introduction and implementation of hepatitis B vaccination programmes in
areas of high endemicity has been very stressful. However, this initial
accomplishment has led to the reassessment of priorities in some countries which 
could undermine these early successes. Work still remains to be done to support
and implement interventions that will bring us closer to the WHO goal and to the 
control of hepatitis B in the community at large. Hepatitis A vaccine strategy
for immunizing toddlers is shifting to those countries with intermediate
endemicity where increasing morbidity in adults is being observed. Accumulating
evidence indicates that such programmes can result in impressive reductions in
the incidence of hepatitis A by herd immunity. Monitoring of these populations to
determine durability of protection will be important to avoid shifting the
infection to the older age population, when symptoms are more likely to occur.
National policies need to consider hepatitis A vaccination in the context of
other public health priorities.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 17958635 [PubMed - indexed for MEDLINE]

88: J Paediatr Child Health. 2008 Apr;44(4):205-7. Epub 2007 Nov 12.

Changing patterns of hepatitis A and E sero-prevalences in children after the
1999 earthquakes in Duzce, Turkey.

Kaya AD, Ozturk CE, Yavuz T, Ozaydin C, Bahcebasi T.

Department of Microbiology, Medical Faculty, Duzce University, Konuralp, Duzce,
Turkey.

AIM: Hepatitis A and E are enteric viral diseases that are characteristically
found in developing countries. Sero-epidemiological data about both infections
showed higher prevalence rates soon after the 1999 earthquakes in Duzce, Turkey. 
The aim of the present study was to evaluate the data 4 years after the
earthquakes. METHODS: The study group included 589 children (72.3% boys) who were
between the ages of 6 months and 17 years (mean age 11.5 years). The children
were separated into three groups: Group 1 (ages 6 months to 5.9 years), Group 2
(ages 6.0-12.9 years) and Group 3 (ages 13.0-17.0 years). Serum anti-hepatitis A 
virus IgG and anti-hepatitis E virus IgG were determined using commercial
enzyme-linked immunosorbent assay kits. The data were tested for statistical
significance with the chi(2)-test. RESULTS: The sero-prevalence rates of
hepatitis A and E were 63.8% and 0.3%, respectively. The sero-prevalence rates of
both hepatitis A and E increased with age, and there was no significant
difference between the genders. Hepatitis A infection was associated with
socio-economic condition, crowded living environment, and education level of the 
family (P < 0.01). CONCLUSIONS: Hepatitis A infection is still common, whereas
hepatitis E infection appears to be relatively rare in paediatric age groups in
Duzce, Turkey.

PMID: 17999670 [PubMed - indexed for MEDLINE]

89: Vaccine. 2007 Dec 12;25(51):8536-48. Epub 2007 Oct 23.

Cost-utility of universal hepatitis A vaccination in Canada.

Bauch CT, Anonychuk AM, Pham BZ, Gilca V, Duval B, Krahn MD.

University of Guelph, Department of Mathematics and Statistics, Guelph, Ontario, 
Canada. cbauch@uoguelph.ca

Hepatitis A (HA) vaccination in Canada is currently targeted toward high-risk
groups. The cost-effectiveness and expected health outcomes of universal
vaccination relative to targeted vaccination in low-incidence countries such as
Canada are currently unknown. Here, we conducted a cost-utility analysis for this
situation, with Canada as the study population. We included vaccine costs, time
costs, infection costs, and public health costs. We assessed a range of possible 
universal vaccination strategies over an 80-year time horizon using multiple cost
perspectives. A dynamic model was used to account for herd immunity. Aggregate
health gains from switching to universal vaccination are modest (10-30 QALYs per 
year). However, a "9+9" strategy that replaces two doses of monovalent hepatitis 
B (HB) vaccine at 9/10 years (universally administered in most provinces) with
two doses of bivalent HA/HB vaccine is cost-saving from the societal perspective.
At a willingness to pay threshold of $50,000/QALY, mean net benefit is +49.4
QALYs (S.D. 12.6) from the societal perspective and +3.8 QALYS (S.D. 3.0) from
the payer perspective for the "9+9" strategy. Net benefit from the payer
perspective is sensitive to the marginal cost of HA/HB vaccine relative to HB
vaccine. Similar conclusions may apply in other countries with low incidence and 
a targeted vaccination policy.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17996339 [PubMed - indexed for MEDLINE]

90: Int J Infect Dis. 2008 May;12(3):270-7. Epub 2007 Nov 7.

Immunogenicity, safety, and interchangeability of two inactivated hepatitis A
vaccines in Chilean children.

Abarca K, Ibánez I, Perret C, Vial P, Zinsou JA.

Centro Médico San Joaquín, Pontificia Universidad Católica de Chile, Marcoleta
391, Santiago, Chile. katia@med.puc.cl

OBJECTIVES: To compare the immunogenicity, safety, and interchangeability of two 
pediatric hepatitis A vaccines, Avaxim 80U-Pediatric and Havrix 720, in Chilean
children. METHODS: In this randomized trial, 332 hepatitis A virus (HAV)
seronegative children from 1 to 15 years of age received two doses of Avaxim, two
doses of Havrix, or Havrix followed by Avaxim, 6 months apart. Anti-HAV antibody 
titers were measured before and 14 days after the first dose of vaccine, and
before and 28 days after the second dose of vaccine. Immediate reactions were
monitored; reactogenicity was evaluated from parental reports. RESULTS:
Seroconversion rates after the first vaccination were 99.4% and 100% for Avaxim
and Havrix, respectively. Anti-HAV geometric mean concentrations (GMCs) were 138 
mIU/ml for Havrix (95% confidence interval (CI): 120; 159) and 311 mIU/ml for
Avaxim (95% CI: 274; 353). GMCs increased to 4008 mIU/ml after two doses of
Havrix, 8537 mIU/ml following two doses of Avaxim, and 7144 mIU/ml in children
who received Havrix with Avaxim as the second dose. Following the first
injection, 36% of subjects given Avaxim and 44% given Havrix reported local
reactions; 38% of subjects in the Avaxim group and 40% in the Havrix group
reported systemic reactions related to vaccination. Solicited reactions were less
frequent after the second dose of Avaxim or Havrix, occurring in 27% to 37% of
subjects. CONCLUSIONS: No significant difference in seroconversion rates was seen
14 days after a single dose of vaccine. A two-dose schedule with either vaccine
or with Havrix/Avaxim provided a strong booster response. Both vaccines were well
tolerated and can be recommended for routine vaccination of Chilean children.
Avaxim 80 may be used to complete a vaccine schedule begun with Havrix 720.

Publication Types: 
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 17988917 [PubMed - indexed for MEDLINE]

91: Eur J Epidemiol. 2008;23(1):45-53. Epub 2007 Nov 3.

Hepatitis A incidence and hospital-based seroprevalence in Italy: a nation-wide
study.

Ansaldi F, Bruzzone B, Rota MC, Bella A, Ciofi degli Atti M, Durando P, Gasparini
R, Icardi G; Serologic Study Group.

Department of Health Sciences, University of Genoa, Via Pastore 1, Genoa, Italy. 
filippo.ansaldi@unige.it

To define the pattern of HAV infection in Italy and to study the differences
among geographic areas (northern, central and southern Italy) and age-classes, we
performed HAV antibody testing on sera collected in 1996-1997 from a large sample
of the Italian population and compared the results with those of other
seroprevalence studies and with incidence data for the period 1985-2005,
calculated by a surveillance system specific for acute viral hepatitis based on
symptomatic cases. A total of 3,561 sera, collected by hospital-based reference
laboratories in 18 out of 20 Italian Regions, were tested; 1,138 (32%, 95% CI:
30.5-33.5) were positive. The age-adjusted prevalence was 60.1% and the
age-specific rates were among the highest rates reported in Europe in the 1990s. 
The age-adjusted seroprevalence showed a significant north-south gradient,
increasing from 55% in northern Italy to 68% in southern Italy. Age and area of
residence were found to be strong predictors of previous HAV infection: the
marked increase in prevalence with increasing age represents a strong cohort
effect. In northern Italy, a marked increase with age was observed beginning with
the 20- to 29-year age-class, whereas in southern Italy, such an increase was
observed beginning with the 12- to 19-year age-class, indicating that northern
Italy preceded southern Italy by 10-20 years in terms of improvements in hygiene 
and sanitation. The incidence of HAV infection shows an evident peak in 1997,
when an outbreak occurred in southern Italy, mainly affecting 15- to 24-year-old 
individuals. In the period from 1998 to 2005, the incidence drastically decreased
(average of 3.2/100,000 inhabitants), reaching a minimum of 2/100,000 inhabitants
in 2005.

PMID: 17978852 [PubMed - indexed for MEDLINE]

92: Am J Gastroenterol. 2008 Jan;103(1):138-46. Epub 2007 Oct 26.

Incidence of HAV and HBV infections and vaccination rates in patients with
autoimmune liver diseases.

Wörns MA, Teufel A, Kanzler S, Shrestha A, Victor A, Otto G, Lohse AW, Galle PR, 
Höhler T.

Department of Internal Medicine I, Johannes Gutenberg-University, Mainz, Germany.

OBJECTIVES: Hepatitis A virus (HAV) or hepatitis B virus (HBV) superinfection is 
associated with an increased mortality in patients with chronic liver diseases
(CLD). Despite official recommendations, it was reported that the vaccination
rate against HAV is low in patients with chronic hepatitis C infection. To
evaluate the situation in patients with autoimmune liver diseases, we conducted a
retrospective cohort study. METHODS: Susceptibility to HAV and HBV infections,
course of HAV and HBV infections, vaccination rates against HAV and HBV, and
efficacy of hepatitis A/B vaccines were evaluated by antibody testing in 225
patients with autoimmune liver diseases during 1,677 person-years. RESULTS:
Susceptibility to HAV/HBV infection was 51/86%. Incidence of HAV/HBV infection
was 1.3/1.4 per 1,000 person-years. One HAV infection occurred, but the patient
recovered spontaneously. Two patients were HBV-infected after receiving an
anti-HBc-positive (antibody to hepatitis B core antigen) donor graft during
orthotopic liver transplantation, and one of them developed chronic HBV
infection. Vaccination rates were 11% (HBV) and 13% (HAV), respectively.
Seventy-six percent of the vaccinated patients (HBV vaccine) developed anti-HBs
(antibody to hepatitis surface antigen) >or=10 UI/L. Ten out of 13 vaccinated
patients, showing a low or nonresponse to hepatitis B vaccine, had concomitant
immunosuppressive therapy. Anti-HAV was detectable in all patients after
administration of HAV vaccine. CONCLUSIONS: Patients with autoimmune liver
diseases have a high susceptibility to HAV and HBV infections. Vaccination rates 
are low in this patient cohort and efficacy of hepatitis B vaccine is reduced due
to immunosuppressive therapy. Improving adherence to vaccine recommendations is
essential to prevent HAV and HBV infections in patients with autoimmune liver
diseases.

Publication Types: 
    Comparative Study

PMID: 17970833 [PubMed - indexed for MEDLINE]

93: World J Gastroenterol. 2007 Nov 21;13(43):5741-4.

Acute pancreatitis in acute viral hepatitis.

Jain P, Nijhawan S, Rai RR, Nepalia S, Mathur A.

Department of Gastroenterology, SMS Medical College, Jaipur, Rajasthan, India.

AIM: To elucidate the frequency and characteristics of pancreatic involvement in 
the course of acute (nonfulminant) viral hepatitis. METHODS: We prospectively
assessed the pancreatic involvement in patients with acute viral hepatitis who
presented with severe abdomimanl pain. RESULTS: We studied 124 patients with
acute viral hepatitis, of whom 24 presented with severe abdominal pain. Seven
patients (5.65%) were diagnosed to have acute pancreatitis. All were young males.
Five patients had pancreatitis in the first week and two in the fourth week after
the onset of jaundice. The pancreatitis was mild and all had uneventful recovery 
from both pancreatitis and hepatitis on conservative treatment. The etiology of
pancreatitis was hepatitis E virus in 4, hepatitis A virus in 2, and hepatitis B 
virus in 1 patient. One patient had biliary sludge along with HEV infection. The 
abdominal pain of remaining seventeen patients was attributed to stretching of
Glisson's capsule. CONCLUSION: Acute pancreatitis occurs in 5.65% of patients
with acute viral hepatitis, it is mild and recovers with conservative management.

PMID: 17963301 [PubMed - indexed for MEDLINE]

94: MMWR Morb Mortal Wkly Rep. 2007 Oct 19;56(41):1080-4.

Update: Prevention of hepatitis A after exposure to hepatitis A virus and in
international travelers. Updated recommendations of the Advisory Committee on
Immunization Practices (ACIP).

Advisory Committee on Immunization Practices (ACIP) Centers for Disease Control
and Prevention (CDC).

In 1995, highly effective inactivated hepatitis A vaccines were first licensed in
the United States for preexposure prophylaxis against hepatitis A virus (HAV)
among persons aged > or =2 years. In 2005, vaccine manufacturers received Food
and Drug Administration approval for use of the vaccines in children aged 12-23
months.

Publication Types: 
    Practice Guideline

PMID: 17947967 [PubMed - indexed for MEDLINE]

95: J Gen Virol. 2007 Nov;88(Pt 11):3039-42.

Bayesian coalescent inference of hepatitis A virus populations: evolutionary
rates and patterns.

Moratorio G, Costa-Mattioli M, Piovani R, Romero H, Musto H, Cristina J.

Laboratorio de Virología Molecular, Centro de Investigaciones Nucleares, Facultad
de Ciencias, Iguá 4225, 11400 Montevideo, Uruguay.

Hepatitis A virus (HAV) is a hepatotropic member of the family Picornaviridae.
Previous studies suggested that HAV may evolve more slowly than other members of 
the family. To estimate HAV substitution rates precisely, we used a Bayesian
Markov chain Monte Carlo (MCMC) approach on temporally sampled HAV VP1
full-length sequences from strains isolated in France. A mean rate of
evolutionary change of 9.76 x 10(-4) nucleotide substitution per site per year
was found. The results also revealed that the synonymous rate found for HAV is
lower than that of other members of the family. Bayesian skyline plots revealed a
sharp decline in the effective number of infections in 1996, coinciding with the 
introduction of HAV vaccine.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17947528 [PubMed - indexed for MEDLINE]

96: N Engl J Med. 2007 Oct 25;357(17):1685-94. Epub 2007 Oct 18.

Comment in:
    Hepatology. 2008 Apr;47(4):1416-8.    J Fam Pract. 2008 Feb;57(2):82.    N Engl J Med. 2007 Oct 25;357(17):1757-9.    N Engl J Med. 2008 Jan 31;358(5):531-2; author reply 532.    N Engl J Med. 2008 Jan 31;358(5):531; author reply 532.

Hepatitis A vaccine versus immune globulin for postexposure prophylaxis.

Victor JC, Monto AS, Surdina TY, Suleimenova SZ, Vaughan G, Nainan OV, Favorov
MO, Margolis HS, Bell BP.

University of Michigan, Ann Arbor, USA.

BACKGROUND: Hepatitis A vaccine administered to persons after exposure to the
hepatitis A virus has not been compared directly with immune globulin, which is
known to be highly effective in preventing hepatitis A when given within 2 weeks 
after exposure to the virus. METHODS: We randomly assigned household and day-care
contacts, 2 to 40 years of age, in Almaty, Kazakhstan, to receive one standard
age-appropriate dose of hepatitis A vaccine or immune globulin within 14 days
after exposure to patients with hepatitis A. Instances of laboratory-confirmed,
symptomatic hepatitis A infection occurring between 15 and 56 days after exposure
were then assessed during active follow-up of all susceptible contacts. RESULTS: 
Of 4524 contacts who underwent randomization, 1414 (31%) were susceptible to
hepatitis A virus and 1090 were eligible for the per-protocol analysis. Among
these contacts, 568 received hepatitis A vaccine and 522 received immune
globulin. Most contacts were children (average age, 12 years), and most received 
prophylaxis during the second week after exposure (average interval after
exposure, 10 days). The baseline characteristics of the contacts were similar in 
the two groups. Symptomatic infection with hepatitis A virus was confirmed in 25 
contacts receiving vaccine (4.4%) and in 17 contacts receiving immune globulin
(3.3%) (relative risk, 1.35; 95% confidence interval, 0.70 to 2.67). CONCLUSIONS:
Low rates of hepatitis A in both groups indicate that hepatitis A vaccine and
immune globulin provided good protection after exposure. Although the study's
prespecified criterion for noninferiority was met, the slightly higher rates of
hepatitis A among vaccine recipients may indicate a true modest difference in
efficacy and might be clinically meaningful in some settings. Vaccine has other
advantages, including long-term protection, and it may be a reasonable
alternative to immune globulin for postexposure prophylaxis in many situations.
(ClinicalTrials.gov number, NCT00139139 [ClinicalTrials.gov].). Copyright 2007
Massachusetts Medical Society.

Publication Types: 
    Comparative Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 17947390 [PubMed - indexed for MEDLINE]

97: Int J STD AIDS. 2007 Oct;18(10):707-10.

Increasing hepatitis A IgG prevalence rate in men who have sex with men attending
a sexual health clinic in London: implications for immunization policy.

O'Riordan M, Goh L, Lamba H.

Department of Sexual Health, Jefferiss Wing, St Mary's Hospital, Paddington,
London, UK. maryoriordan@doctors.net.uk

The aims of this study were to audit an immunization policy to vaccinate men who 
have sex with men (MSM) attending a large London sexual health clinic, and to
undertake an approximate cost analysis of different strategies, using the
estimated prevalence rate of anti-hepatitis A virus (HAV) immunoglobulin G (IgG).
A retrospective study of the seroprevalence of anti-HAV IgG among MSM was
conducted for a 12-month period, involving 395 homosexual or bisexual men
attending the genitourinary medicine clinic at St Mary's Hospital, London, for
the first time. Overall seroprevalence of anti-HAV IgG in the 2004 population
surveyed was 46.6% (140/300); 75.1% (300/395) were offered screening on their
first visit and 49.9% (197/395) were offered vaccination. We concluded that
anti-HAV IgG screening prior to vaccination of MSM in an area of relatively low
prevalence of HAV is still the most cost-effective approach. The audit data also 
showed that in 2004 the British Association for Sexual Health and HIV targets for
hepatitis A screening and vaccination were not reached. If a one-dose policy is
seen to establish long-term immunity, then the cost of hepatitis A prevention
will be drastically reduced.

PMID: 17945051 [PubMed - indexed for MEDLINE]

98: J Med Virol. 2007 Dec;79(12):1802-10.

Population-based study on the seroprevalence of hepatitis A, B, and C virus
infection in Amsterdam, 2004.

Baaten GG, Sonder GJ, Dukers NH, Coutinho RA, Van den Hoek JA.

Department of Infectious Diseases, Municipal Health Service (GGD) Amsterdam,
Nieuwe Achtergracht 100, PO Box 2200, 1000 CE Amsterdam, The Netherlands.
gbaaten@ggd.amsterdam.nl

In order to enhance screening and preventive strategies, this study investigated 
the seroprevalence of hepatitis A, B, and C in the general adult urban population
and in subgroups. In 2004, sera from 1,364 adult residents of Amsterdam were
tested for viral markers. Sociodemographic characteristics were collected using a
standardized questionnaire. For hepatitis A, 57.0% was immune. Of
first-generation immigrants from Turkey and Morocco, 100% was immune. Of all
Western persons and second-generation non-Western immigrants, approximately half 
was still susceptible. For hepatitis B, 9.9% had antibodies to hepatitis B core
antigen (anti-HBc) and 0.4% had hepatitis B surface antigen. Anti-HBc
seroprevalences were highest among first-generation immigrants from Surinam,
Morocco, and Turkey, and correlated with age at the time of immigration, and
among men with a sexual preference for men. Seroprevalence among
second-generation immigrants was comparable to Western persons. The
seroprevalence of hepatitis C virus antibodies was 0.6%. In conclusion, a country
with overall low endemicity for viral hepatitis can show higher endemicity in
urban regions, indicating the need for differentiated regional studies and
prevention strategies. More prevention efforts in cities like Amsterdam are
warranted, particularly for hepatitis A and B among second-generation immigrants,
for hepatitis B among men with a sexual preference for men, and for hepatitis C. 
Active case finding strategies are needed for both hepatitis B and C. (c)
Wiley-Liss, Inc.

PMID: 17935187 [PubMed - indexed for MEDLINE]

99: J Hosp Infect. 2007 Oct;67(2):175-81. Epub 2007 Oct 4.

Molecular characterization of an acute hepatitis A outbreak among healthcare
workers at a Korean hospital.

Park JY, Lee JB, Jeong SY, Lee SH, Lee MA, Choi HJ.

Department of Internal Medicine, Ewha Womans University School of Medicine,
Seoul, Korea.

The seroprevalence of hepatitis A virus (HAV) antibodies is low in young adults
in Korea. From May to July 2005, 17 cases of HAV were reported from healthcare
workers (HCWs) in a hospital intensive care unit (ICU). We looked for the
presence of anti-HAV IgM from all patients in the medical-surgical ICU with
elevated aspartate aminotransferase (AST) and alanine aminotransferase (ALT) and 
screened AST and ALT levels in all HCWs who came into contact with two suspected 
index cases. Once the outbreak was confirmed, the molecular subtypes of HAV from 
the blood of HCWs were determined. Index cases and a transmission route were
identified, and intervention strategies applied to control the outbreak. The 17
HCW cases included 13 nurses and four doctors aged 22-32 years, who each suffered
acute HAV infection during the study period. The possible transmission of HAV was
via the faecal-oral route from bedridden patients with diarrhoea. All HCWs were
positive for anti-HAV IgM and eight were positive for HAV RNA. Analysis of the
VP1-2A region of each isolate showed genotype IA in five strains and
co-circulation of genotypes IA and IB in the others. This HAV outbreak highlights
the importance of standard infection control precautions within a hospital.
Molecular study of patients' blood would be useful for clarifying the
epidemiology of a suspicious HAV outbreak in a hospital.

PMID: 17919777 [PubMed - indexed for MEDLINE]

100: Acta Paediatr Taiwan. 2007 May-Jun;48(3):131-4.

Comment in:
    Acta Paediatr Taiwan. 2007 May-Jun;48(3):105-6.

Acute hepatitis A infection in children: a 20-year experience of a medical center
in Southern Taiwan.

Chen YC, Huang LT, Wang SM, Tiao MM, Liu JW.

Department of Pediatrics, Chang Gung Memorial Hospital-Kaohsiung Medical Center, 
Chang Gung University College of Medicine, Kaohsiung, Taiwan.

BACKGROUND: Taiwan is currently nonendemic for hepatitis A infection, but
sporadic cases are reported occasionally. The presenting symptoms of acute
hepatitis A (AHA) infection in children are often nonspecific and may be easily
misdiagnosed as general gastrointestinal illness. METHODS: We conducted this
study to identify the relevant presenting symptoms and laboratory findings of AHA
in children. The medical records of all patients younger than 18 years old
admitted to Kaohsiung Chang Gang Memorial Hospital from July 1986 to June 2004
under the diagnosis of AHA were reviewed. There were 29 pediatric patients
admitted with the diagnosis of AHA, including 16 male patients and 13 female
patients. RESULTS: Poor appetite, malaise, abdominal pain, vomiting and fever
were the leading constitutional symptoms. Jaundice and tea-colored urine were the
most relevant hepatobiliary presentations. Elevation of aspartate
aminotransferase, alanine aminotransferase, alkaline phosphatase, direct and
indirect bilirubin was common, although other hematology and biochemistry
examinations were within normal limits on most occasions. There was no mortality 
in our series. A slightly increasing prevalence of AHA was noted over the two
decades of the study period, although it was not statistically significant.
CONCLUSIONS: Our results found that children with AHA tended to present with
non-specific gastrointestinal symptoms and acute liver function deterioration.
Elevation of hepatic aminotransferase and alkaline phosphatase with cholestasis
was common.

PMID: 17912984 [PubMed - indexed for MEDLINE]

101: Turk J Pediatr. 2007 Apr-Jun;49(2):199-202.

Hepatitis A super infection as a cause of liver failure in a child with Wilson's 
disease.

Ozçay F, Canan O, Akcan B, Bilezikçi B.

Department of Pediatrics, Başkent University, Faculty of Medicine, Ankara,
Turkey.

Infection with hepatitis A virus can cause severe or even fatal illness in
patients with chronic liver disease. Here we describe a seven-year-old girl who
presented as acute liver failure and was diagnosed with Wilson's disease and
later with coexistent hepatitis A infection. Wilson's disease was demonstrated on
the basis of low ceruloplasmin, high urinary copper excretion, histological
evidence of cirrhosis, and high biochemical estimation of liver copper
concentration. Hepatitis A was diagnosed serologically. Our case suggests that
acute hepatitis A may play a part in the acute decompensation seen in some cases 
of unrecognized Wilson's disease. We also emphasize the importance of prevention 
measures of hepatitis A infection in patients with chronic liver disease.

Publication Types: 
    Case Reports

PMID: 17907522 [PubMed - indexed for MEDLINE]

102: Epidemiol Infect. 2008 Aug;136(8):1027-34. Epub 2007 Sep 25.

Epidemiological and virological characterization of a large community-wide
outbreak of hepatitis A in southern Italy.

Pontrelli G, Boccia D, DI Renzi M, Massari M, Giugliano F, Celentano LP, Taffon
S, Genovese D, DI Pasquale S, Scalise F, Rapicetta M, Croci L, Salmaso S.

Centro Nazionale di Epidemiologia, Sorveglianza e Promozione della Salute,
Istituto Superiore di Sanità, Roma, Italy.

A large outbreak of hepatitis A virus (HAV) infection occurred in 2004 in
Campania, a region of southern Italy, with 882 cases reported between 1 January
and 1 August. The local public health authorities and the Italian National
Institute of Health carried out investigations in order to characterize the
agent, identify the source of infection and the route of transmission, and
implement appropriate control measures. A web-based reporting system enhanced the
flow of information between public health authorities, providing real-time
epidemic curves and frequency distributions. The same 1B HAV genotype was found
in 90% of sera from a subset of patients with acute disease, suggesting a local
common source. A case-control study in the municipality with the highest attack
rate showed that raw seafood consumption, in particular if illegally sold in
water, was strongly associated with HAV illness. Samples of seafood
systematically collected from retailers were found contaminated by HAV.

PMID: 17892633 [PubMed - indexed for MEDLINE]

103: Am J Prev Med. 2007 Oct;33(4):346-52.

Hepatitis A 2004 vaccination in children: methods and findings of a survey in two
states.

Fiore A, Baxter LC, Bell BP, Hershow R, Passaro D, Twiddy S, Baxter R, Levy PS.

National Center for Infectious Diseases, Centers for Disease Control and
Prevention, 4770 Buford Highway NE, Atlanta, GA 30341, USA.

BACKGROUND: Hepatitis A vaccine coverage estimates needed for surveillance and
vaccine policy decisions are not readily available for children older than 35
months or for adolescents. This article reports methodology developed for
obtaining such estimates by telephone survey with and without provider record
verification. METHODS: A random-digit-dial telephone survey with provider
verification was conducted in Arizona and Oregon in 2004-2005 to obtain coverage 
estimates for children aged 2.5 to 15 years based on parental reports from
telephone survey data alone, and from multiple logistic regressions using both
telephone survey and provider data. Analysis was performed during 2006. RESULTS: 
Vaccination information was collected from parents of 1266 children, and provider
verification from 488. Telephone survey and provider record-based hepatitis A
vaccine coverage (one or more doses) was 60% and 65%, respectively, in Arizona,
and 39% and 26%, respectively, in Oregon. Children who were younger, lived in
metropolitan areas, or were Hispanic or nonwhite had significantly higher
coverage; parents with immunization records provided more-accurate information.
While a logistic model-based estimator developed using both parent and provider
data performed slightly better than the estimator based on parent data alone,
they differed mostly in the subgroups that had small sample sizes. CONCLUSIONS:
These are the first statewide provider-verified hepatitis A vaccine coverage
estimates for children older than 35 months and indicate that telephone survey
estimates as developed using this methodology could prove useful for immunization
surveillance activities if interpreted cautiously.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 17888861 [PubMed - indexed for MEDLINE]

104: Am J Med Sci. 2007 Sep;334(3):180-3.

Hepatitis A outbreak activity in the United States: responding to a
vaccine-preventable disease.

Craig AS, Watson B, Zink TK, Davis JP, Yu C, Schaffner W.

Tennessee Department of Health, Nashville, Tennessee 37247, USA.
allen.craig@state.tn.us

BACKGROUND: The occurrence of hepatitis A in the United States is heterogeneous
because of disease cycles with substantial variation in incidence among states
and involvement of numerous behavioral risk factors. In spite of the Advisory
Committee on Immunization Practices' (ACIP) 1999 recommendation for routine
hepatitis A immunization in states with high rates of disease and the fact that
disease rates are at a historic low, outbreaks continue to occur. METHODS: We
reviewed outbreaks of hepatitis A in the United States occurring from 1994
through 2004. We searched PubMed, ProMed, Google, and the CDC Foodborne Disease
Outbreak and Epi-X Internet sites to ascertain the number and type of hepatitis A
outbreaks. The CDC's MMWR publication and the Hepatitis Control Report were also 
searched. RESULTS: A total of 256 hepatitis A outbreaks were identified from 1994
through 2004. The mean number of outbreaks was 23 per year (median 25). The
number of outbreaks in states with traditionally low/intermediate endemic rates
of hepatitis A remained relatively constant during the study period. Outbreaks
declined significantly (P = 0.01) in states with previously high rates of
disease--most of which have implemented hepatitis A vaccination programs.
CONCLUSIONS: Outbreaks of hepatitis A continue to occur in the United States
despite the licensure of two safe and effective vaccines in 1995 and the apparent
decline in the number of outbreaks in states with previously high rates of
hepatitis A. The recent ACIP recommendation for universal hepatitis A vaccination
at age 1 year in all states will contribute to a further reduction in hepatitis A
outbreaks.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17873531 [PubMed - indexed for MEDLINE]

105: Pediatr Infect Dis J. 2007 Aug;26(8):711-5.

Hepatitis A as an etiologic agent of acute liver failure in Latin America.

Ciocca M, Moreira-Silva SF, Alegría S, Galoppo MC, Ruttiman R, Porta G, Da
Silvera TR, Rubio P, Macias M, Cervantes Y, Avila-Aguero ML, Clemens SA, Clemens 
R, Weil J.

Hospital Nacional de Pediatría Juan P Garrahan, Buenos Aires, Argentina.

BACKGROUND: This prospective, multicenter study examined the importance of
hepatitis viruses as etiological agents of acute liver failure (ALF) and the
outcome of ALF cases in Latin American children and adolescents. METHODS: The
study was conducted for minimum 12 months in 9 centers in Argentina, Brazil,
Chile, Colombia, Costa Rica, and Mexico during 2001-2002. Hospitalized patients
aged 1-20 years with a suspected diagnosis of ALF were included in the study and 
tested for serologic markers for hepatitis A, B, and C viruses. RESULTS: Of the
106 patients enrolled, 88 were included in the analysis. Median age was 5 years, 
and 55% with ALF were aged 1-5 years. A total of 37 individuals (43%) tested
positive for anti-hepatitis A virus (HAV) immunoglobulin M (IgM) as marker of
acute HAV infection; one was positive for anti-hepatitis B core antigen IgM and
negative for hepatitis B surface antigen. None had markers of hepatitis C virus
infection. Mortality rates in the overall study cohort (45%) and for those who
tested anti-HAV IgM positive (41%) were similar. Forty-one percent of all
patients and 46% of those positive for anti-HAV IgM underwent transplantation.
The mortality rate in those with liver transplantation was half of that in
patients who were not transplanted (28% versus 57%). CONCLUSIONS: HAV was the
main etiologic agent of ALF in the population studied.

Publication Types: 
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 17848883 [PubMed - indexed for MEDLINE]

106: Vaccine. 2007 Oct 10;25(41):7125-31. Epub 2007 Aug 13.

Prevalence and correlates of hepatitis A among adult drug users: the significance
of incarceration and race/ethnicity.

Latimer WW, Moleko AG, Melnikov A, Mitchell M, Severtson SG, von Thomsen S,
Graham C, Alama D, Floyd L.

Department of Mental Health, Johns Hopkins University Bloomberg School of Public 
Health, 624 N. Broadway Street, 850 Hampton House, Baltimore, MD 21205, USA.
wlatimer@jhsph.edu

This report examines associations between hepatitis A virus (HAV) infection
prevalence and a history of incarceration in jail or a correctional facility
among a population of drug users in Baltimore stratified by African American and 
white racial/ethnic status. The study sample consisted of 509 non-injection and
injection drug users recruited from inner-city neighborhoods of the Baltimore
metropolitan region. The baseline prevalence of HAV infection was 36.9% (N=188). 
One-fourth (25.5%) of the sample reported no lifetime history of incarceration,
44.6% reported incarceration in a local jail in their lifetime, and 29.9%
reported incarceration in a correctional facility in their lifetime. In the
multivariate logistic analysis, HAV infection prevalence was higher for whites
(44.3%) [adjusted odds ratio (AOR)=2.3, 95% CI=1.5-3.5] when compared to African 
Americans (30.5%) adjusting for gender, age, and education. In the analysis
stratified by race/ethnicity, as anticipated, jail incarceration and correctional
facility incarceration were each independently associated with elevated HAV
prevalence among white drug users. African American drug users with a high school
diploma had significantly lower HAV infection prevalence when compared to African
American drug users who did not graduate from high school. Heightened HAV
prevalence among white drug users compared to African American drug users is
noteworthy given the opposite association of HAV infection prevalence and these
two racial/ethnic groups in the general population. Since millions of
incarcerated drug users in the US return to society each year, the results
suggest that incorporating systematic HAV screening, prevention, and treatment
programs within correctional systems represents a vital yet underutilized
strategy to reduce HAV transmission in society as a whole.

Publication Types: 
    Research Support, N.I.H., Extramural

PMID: 17766016 [PubMed - indexed for MEDLINE]

107: Rev Panam Salud Publica. 2007 Jun;21(6):345-56.

Cost-effectiveness of childhood hepatitis A vaccination in Argentina: a second
dose is warranted.

Ellis A, Rüttimann RW, Jacobs RJ, Meyerhoff AS, Innis BL.

Secretariat of Health of the City of Buenos Aires, Buenos Aires, Argentina.

OBJECTIVES: To investigate the cost-effectiveness of childhood vaccination
against hepatitis A in the five geographic regions of Argentina, and to determine
whether adding a second dose to the current one-dose schedule would provide
health gains justifying its added cost. METHODS: A Markov model was used to
consider four immunization options for the 2005 birth cohort: (1) no vaccination;
(2) vaccination at 12 months of age, (3) vaccinations at 12 and 72 months of age;
or (4) vaccinations at 12 and 18 months of age. Hepatitis A costs and
consequences were predicted over 50 years. The cost-effectiveness of first and
second vaccine doses was assessed through a range of vaccine prices and
assumptions regarding the duration of vaccine protection. Costs and health gains 
(measured in quality-adjusted life years) were adjusted to present values using a
3% annual discount rate. RESULTS: The one-dose vaccination policy is predicted to
reduce each birth cohort member's 50-year probability of overt hepatitis A from
7.2% to 4.1%. A second dose would reduce the probability to between 2.0% and
2.2%. Vaccination at 12 months of age, at 12 and 72 months, or at 12 and 18
months would reduce cases among personal contacts by 82%, 87%, and 92%,
respectively. The first vaccine dose would meet accepted standards of
cost-effectiveness in each region, and reduce costs in the Northeast, Central,
and South regions. Adding a second dose at age 18 months would be cost-effective 
in each region, and further reduce costs in the Cuyo region. If the duration of
protection with one dose is less than anticipated, the second dose would be more 
cost-effective. CONCLUSIONS: Greater health gains are derived from the first than
second hepatitis A vaccine dose. However, this analysis supports the
cost-effectiveness of providing both first and second doses to Argentina's
children.

Publication Types: 
    Comparative Study
    Evaluation Studies

PMID: 17761046 [PubMed - indexed for MEDLINE]

108: Mil Med. 2007 Jul;172(7):787-93.

Rising hepatitis A immunity in U.S. military recruits.

Nevin RL, Niebuhr DW.

Army Medical Surveillance Activity, US Army Center for Health Promotion and
Preventive Medicine, Silver Spring, MD 20910, USA.

BACKGROUND: The U.S. military immunizes new recruits against hepatitis A. Since
2001, immunization with the hepatitis A vaccine has been recommended for civilian
adolescents in higher risk areas. Recently, the Armed Forces Epidemiological
Board recommended serologic screening where feasible to reduce redundant recruit 
immunizations. OBJECTIVES: The purpose of this study was to determine hepatitis A
seroprevalence in recruit populations to inform screening policy. METHODS: Banked
serum from a sample of military recruits (n = 2,592) in 2004 was tested for total
antibody to hepatitis A (anti-hepatitis A virus (HAV)). RESULTS: The overall
anti-HAV seroprevalence was 12.0% (95% confidence interval, 10.8%-13.3%).
Adjusted to the age distribution of the 18- to 34-year-old population, the
seroprevalence was 11.9% (10.5%-13.4%). The lowest seroprevalence was noted in
the 1984 birth cohort, with significantly higher seroprevalence among younger
recruits. CONCLUSIONS: Rising hepatitis A immunity among successive birth cohorts
suggests increasing compliance with immunization recommendations. In anticipation
of rising population immunity, universal screening of military recruits for
anti-HAV is recommended.

Publication Types: 
    Research Support, U.S. Gov't, Non-P.H.S.

PMID: 17691697 [PubMed - indexed for MEDLINE]

109: West Indian Med J. 2006 Dec;55(6):409-13.

Serum leptin levels in children with acute viral hepatitis A.

Caner I, Selimoglu MA, Yazgi H, Ertekin V.

Department of Paediatrics, Faculty of Medicine, Atatürk University, Erzurum,
Turkey.

OBJECTIVES: In acute viral hepatitis A (AVH-A), involvement of the liver is
through cytotoxic cells and cytokine levels are increased Immune response of the 
host determines the severity of the disease. Leptin stimulates cytokines,
therefore, the authors hypothesized that the relationship between leptin and
cellular immunity might cause different clinical presentations of the disease.
METHODS: Twenty-eight children with AVH-A and 10 healthy children formed the
basis of the study. Serum leptin, C-reactive protein (CRP) and
alpha-1-antitrypsin (A1AT) levels were determined RESULTS: There was significant 
positive correlation between body mass index (BMI) and leptin levels both in
patients and controls (p = 0.003 and p = 0.001 respectively). No significant
difference in serum leptin, CRP or A1AT levels between patients and controls was 
detected (p > 0.05). Presence of icterus or fulminant hepatic failure (FHF) did
not affect serum leptin level (p > 0.05). Mean A1AT level was significantly
higher in children with FHF (p < 0.05). On the 30th day of admission, mean BMI,
weight and leptin levels increased (p < 0.01, p < 0.01 and p < 0.05 respectively)
and mean A1AT level decreased (p < 0.01). CONCLUSION: Leptin levels are not
altered in children with AVH-A. In the convalescence period, leptin increased
parallel to BMI. It is suggested that expected increment in leptin due to
inflammation might be balanced with the decrease due to loss of appetite during
acute illness or it might be entirely due to loss of production.

PMID: 17691236 [PubMed - indexed for MEDLINE]

110: Saudi J Kidney Dis Transpl. 2007 Sep;18(3):422-5.

Acute renal failure in a patient with non-fulminant hepatitis A infection.

Parakkadavathu RT, Pisharath SV, Chekkura AP, Khandekar A, Soni SS, Parameswaran 
RM, Melothvalapil A.

Krishna Nursing Home, Kanhangad, India. rakeshtp@yahoo.com

Acute viral hepatitis A is a common cause of jaundice with a very low mortality. 
Acute renal failure occurs very rarely in hepatitis A. We report a case of
non-fulminant hepatitis A in a 45-year-old man complicated by acute renal
failure. The patient was treated successfully with hemodialysis resulting in
complete recovery. Kidney biopsy was not performed in view of improving clinical 
picture.

Publication Types: 
    Case Reports

PMID: 17679757 [PubMed - indexed for MEDLINE]

111: J Water Health. 2007 Jun;5(2):229-40.

Hepatitis A virus in surface water in South Africa: what are the risks?

Venter JM, van Heerden J, Vivier JC, Grabow WO, Taylor MB.

Department of Medical Virology, Pathology, Faculty of Health Sciences, University
of Pretoria, South Africa. iventer@med.up.ac.za

The aim of this study was to assess the potential risk of infection constituted
by HAV to persons using surface dam and river water for domestic and recreational
purposes. It estimates the potential risk using a deterministic exponential risk 
assessment model with mean values and conservative assumptions. Hepatitis A virus
was detected in 17.5% of river and 14.9% of dam water samples tested. The number 
of indicator organisms in these sources exceeded drinking and recreational water 
quality guidelines set by the United States Environmental Protection Agency (US
EPA), indicating possible health risks to recreational water users. Based on the 
available data and taking all the assumptions into consideration, the probability
of infection (Pinf) to the higher socio-economic population using the river water
for recreational purposes was 1.1 x 10(-3) per day and 3.3 x 10(-1) per annum if 
100 ml was ingested per day. For recreation in the dam water the Pinf value was
1.2 x 10(-4) per day and 4.2 x 10(-2) per annum. For the lower socio-economic
population, risk values for drinking purposes (2 L day(-1)) were ten-fold
greater. These surface waters therefore did not conform to the US EPA guidelines 
of 1 infection per 10,000 consumers per year for drinking water or eight
gastrointestinal illnesses per 1,000 bathers per day in environmental waters used
for recreational purposes. This is the first risk assessment study addressing the
risk of infection by HAV in surface water to different socio-economic populations
in South Africa.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17674572 [PubMed - indexed for MEDLINE]

112: J Gastroenterol. 2007 Jul;42(7):560-6. Epub 2007 Jul 25.

Erratum in:
    J Gastroenterol. 2008 Feb;43(2):179.

Analysis of hepatitis A virus protein 2B in sera of hepatitis A of various
severities.

Fujiwara K, Yokosuka O, Imazeki F, Miki M, Suzuki K, Okita K, Tanaka E, Omata M.

Department of Medicine and Clinical Oncology, Graduate School of Medicine, Chiba 
University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.

BACKGROUND: In our recent study of the full-length hepatitis A virus (HAV) genome
from some patients with fulminant hepatitis and acute hepatitis, possible
associations were suggested between the severity of hepatitis A and the amino
acid substitutions in the nonstructural protein 2B. We therefore analyzed HAV 2B 
from many patients with various clinical disease severities. METHODS: Serum
samples from 30 Japanese patients with sporadic hepatitis A from five widely
separated regions of Japan, comprising nine patients with fulminant hepatitis
(FH), six with severe acute hepatitis (AHs), and 15 with acute hepatitis (AH),
were examined for HAV RNA. The entire sequences of HAV 2B were analyzed. RESULTS:
Compared with the sequence of the wild-type HAV strain GBM, nucleotide sequences 
of 2B had homology of 94.5 +/- 1.0% in FH, 95.2 +/- 1.2% in AHs, and 95.1 +/-
1.8% in AH. Deduced amino acid sequences had homology of 97.5 +/- 2.1% in FH,
97.9 +/- 2.4% in AHs, and 98.5 +/- 1.3% in AH. Differences were not statistically
significant among the three groups. The average number of amino acid mutations
between amino acids 100 and 200 was 5.0 +/- 5.2 per case in FH, 4.0 +/- 6.0 in
AHs, and 1.9 +/- 2.9 in AH. The differences between FH and AH, AHs and AH, and
between severe cases (FH and AHs) and nonsevere cases (AH) were not statistically
significant (P = 0.13, P = 0.45, and P = 0.10, respectively). CONCLUSIONS: There 
were no obvious differences in the sequences among FH, AHs, and AH throughout the
2B region, but there seemed to be more mutations in the strains obtained from FH 
and AHs patients than in those obtained from AH patients in the central part of
HAV 2B.

PMID: 17653652 [PubMed - indexed for MEDLINE]

113: J Gastroenterol Hepatol. 2008 Jul;23(7 Pt 2):e105-10. Epub 2007 Jul 20.

Impaired function of CD4+/CD25+ T regulatory lymphocytes characterizes the
self-limited hepatitis A virus infection.

Perrella A, Vitiello L, Atripaldi L, Sbreglia C, Grattacaso S, Bellopede P,
Patarino T, Morelli G, Altamura S, Racioppi L, Perrella O.

Department of Hepatogastroenterology and Immunology, VII Division of Infectious
Disease and Immunology, Hospital D Cotugno, Naples, Italy.
alex.perrel@virgilio.it

BACKGROUND AND AIM: Hepatitis A virus (HAV) causes a transient illness leaving
permanent protection against reinfection. Few data are available on the
regulatory mechanisms involved in the CD4+ T helper activation. We aimed to
investigate the frequency and function of CD3+/CD4+/CD25+ T cells with regulatory
function (Tregs) during acute HAV infection. METHODS: We enrolled 35 consecutive 
patients and 15 healthy donors, enumerated Tregs by flow cytometry assay and
evaluated, after immunomagnetical sorting with magnetic beads, their ability to
inhibit the proliferation of CD4+/CD25- T lymphocytes at different ratios (1:1,
1:10, 1:20). RESULTS: All patients had the usual course of infection. Our
immunological analysis showed Tregs frequency in these patients (6.5% [range,
5-8.8%]; 36 [range, 10-87] cells) did not have any statistical difference
compared with healthy donors (6% [range, 5-8%]; 48 (range, 23-71) cells), while
their ability to suppress CD4+/CD25- was drastically reduced at different ratios 
(Mann-Whitney U-test; ratio 1:1, 93% vs 72%, z = -3.34, P < 0.0001; ratio 1:10,
86% vs 51%, z = -4.04, P < 0.001; ratio 1:20, 56% vs 30%, z = -3.43, P < 0.0001).
After the seroconversion, CD4+/CD25+ frequency and function in HAV-infected
patients did not differ from healthy individuals. CONCLUSION: CD4+/CD25+ T cells 
seem to be impaired in their function during the HAV acute infection. This
evidence might help to determine an optimal T helper cell immune network that is 
a predisposing factor for a self-limiting disease.

PMID: 17645467 [PubMed - indexed for MEDLINE]

114: Int J Infect Dis. 2008 Jan;12(1):3-11. Epub 2007 Jul 20.

The underestimated risk of hepatitis A and hepatitis B: benefits of an
accelerated vaccination schedule.

Keystone JS, Hershey JH.

Division of Infectious Disease, Department of Medicine, Tropical Disease Unit,
Toronto General Hospital, University of Toronto, Toronto, Ontario M5G 2C4,
Canada. jay.keystone@utoronto.ca

Hepatitis A virus (HAV) and hepatitis B virus (HBV) are vaccine-preventable.
Current recommendations advocate vaccination of non-immune adults at risk of
exposure, including travelers to HAV or HBV endemic areas, individuals with high 
risk of contracting a sexually transmitted infection, and some correctional
facility inmates. We review the use of an accelerated schedule to administer the 
combination hepatitis A and hepatitis B vaccine (Twinrix). Administering three
doses over three weeks and a fourth at 12 months provides rapid initial
protection of most individuals for whom the standard 6-month vaccination schedule
would not be suitable, including last-minute travelers and short-term
correctional facility inmates. Furthermore, we consider the role of a universal
vaccination strategy in preventing the spread of HAV and HBV.

Publication Types: 
    Review

PMID: 17643334 [PubMed - indexed for MEDLINE]

115: South Med J. 2007 Jul;100(7):683-5.

Does the race or gender of hepatitis C infected patients influence physicians'
assessment of hepatitis A and hepatitis B serologic status?

Ramsay DB, Friedman M, Borum ML.

Division of Gastroenterology and Liver Disease, George Washington University
Medical Center, Washington, DC 20037, USA. dramsay@gwu.edu

BACKGROUND: HCV infection with concurrent or superinfection with HAV or HBV has
the potential to worsen the liver status of HCV-infected individuals. This study 
evaluates if patients' race or gender influenced whether HAV or HBV serologic
status was determined for the purpose of providing immunization. METHODS: Medical
records of consecutive African-American and white patients referred for
management of HCV were evaluated to determine whether the referring physicians
had obtained HAV and HBV serology. RESULTS: Race and gender analysis revealed a
statistically significant difference (P < 0.0001) in HAV testing of
African-American and white patients, a statistically significant difference in
HAV (P < 0.0001) and HBV (P < 0.0001) testing of African-American and white men, 
and a statistically significant difference (P = 0.0026) in HBV testing of
African-American and white women. CONCLUSION: HCV-infected individuals were
inconsistently tested for HAV and HBV. Patients' race, but not gender, had a
significant impact upon whether HCV-infected individuals were tested for HAV and 
HBV.

PMID: 17639747 [PubMed - indexed for MEDLINE]

116: Med Arh. 2007;61(2):91-3.

Epidemiology of the viral hepatitis A at the Zenica municipality ara in period
from 1987 until 2003.

Tandir S, Zvizdic S, Hamzic S, Alickovic I.

Cantonal Public Health Institute, Zenica. tandirsa@yahoo.co.uk

Viral hepatitis A is an endemic disease with periodic epidemics, or sporadic
cases within endemic areas. It is present in a majority of world countries, more 
often in undeveloped ones. In our country it occurs occasionally, so it still
cannot be considered as solved problem. This is because Bosnia and Herzegovina
until 1990 was in the group of countries with the largest hepatitis A morbidity
in Europe, and municipality Zenica within B&H with the largest morbidity in the
period from 1987 until 1996. By studying the occurrence of the viral hepatitis A 
according to age groups, we can notice that the largest number of patients is at 
the age between 7 and 18 years (school children and youth) with 68.86% of
baseline, than follows patients up to 6 years of age with 15.34%. In analysis of 
occurrence season, it is noticed that disease have a season features with the
peak occurrence during November and December. Regarding the area of living, it is
noticed that the disease occurs significantly less frequently among urban than
rural and suburban population (78%). Among total number of patients within the
period of epidemic we have registered 82.0% of patients, and only 18.0% was
occasional cases. In majority of cases virus spreads by contact, which is the
consequence of poor hygiene and sanitation that was, or still are present in the 
rural areas, because of inadequate infrastructure and lack of sufficient quantity
of clean drinking water, or to say low level of health knowledge among rural
population.

PMID: 17629141 [PubMed - indexed for MEDLINE]

117: Rev Inst Med Trop Sao Paulo. 2007 May-Jun;49(3):155-7.

Prevalence of antibodies against hepatitis A virus among the Kuikuro and Kaiabi
Indians of Xingu National Park, Brazil.

Lafer MM, de Moraes-Pinto MI, Weckx LY.

Division of Pediatric Infectious Diseases, Federal University of São Paulo
(UNIFESP-EPM), SP/Brazil. manulafer@uol.com.br

A seroprevalence study to detect total antibodies against Hepatitis A Virus was
done with 220 samples from 589 Native Indians from Xingu National Park, Brazil,
in five Kaiabi and Kuikuro villages, the most populous ethnic groups. Using a
commercial immunoassay kit we detected 97.7% positive samples (95% Confidence
Interval: 95%-99%). We noticed a precocious seroconversion, before the age of six
years, when the disease is usually asymptomatic. These results are similar to
those found in the literature in non-Indian population studies of the Northern,
Northeastern and West Central regions of Brazil. They suggest that it is not
necessary to introduce vaccination against Hepatitis A in these highly endemic
populations.

PMID: 17625692 [PubMed - indexed for MEDLINE]

118: J Travel Med. 2007 Jul-Aug;14(4):248-53.

Epidemiology of travel-associated and autochthonous hepatitis A in Austrian
children, 1998 to 2005.

Rendi-Wagner P, Korinek M, Mikolasek A, Vécsei A, Kollaritsch H.

Department of Specific Prophylaxis and Tropical Medicine, Centre for Physiology
and Pathophysiology, Medical University Vienna, Vienna, Austria.
pamela.rendi-wagner@meduniwien.ac.at

BACKGROUND: In Austria, being an area of low hepatitis A endemicity, every year, 
several cases of this infectious disease are reported. The aim of the present
study was to provide data on disease and hospitalization of children below the
age of 15 for imported and autochthonous hepatitis A in Austria. METHODS:
Nationwide, active, hospital-based surveillance during the period 1998 to 2005.
RESULTS: During this 8-year observation period, 413 children below 15 years of
age were hospitalized with acute hepatitis due to infection with hepatitis A .
The mean annual incidence of hospitalization per 100,000 population was 3.8, with
a decreasing trend from 1998 to 2005. The mean length of hospital stay
attributable to hepatitis A was 6.5 days. The mean annual number of days of
hospitalization attributable to acute hepatitis A infection in children below 15 
years of age was 335 days. Information on origin of infection was available in
48% of the reports, the majority of which (69%) were in consequence of infection 
import. The mean annual incidence of travel-associated, hospitalized hepatitis A 
cases was 1.3 per 100,000, showing a lesser decrease rate over the observation
period than the total hospitalization incidence. CONCLUSIONS: In an area of low
hepatitis A endemicity such as Austria, hospitalization incidence of children is 
still at a considerable level. Our findings contribute to an open discussion
about universal childhood vaccination.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17617847 [PubMed - indexed for MEDLINE]

119: BMC Infect Dis. 2007 Jul 4;7:73.

Declining hepatitis A seroprevalence in adults in Catalonia (Spain): a
population-based study.

Domínguez A, Bruguera M, Plans P, Espuñes J, Costa J, Plasencia A, Salleras L.

Directorate of Public Health, Generalitat of Catalonia, Travessera de les Corts, 
Barcelona, Spain. angela.dominguez@ub.edu

BACKGROUND: One of the main uses of seroprevalence studies it to evaluate
vaccination programmes. In 1998, a programme of universal vaccination of
preadolescents in schools with the hepatitis A vaccine was begun in Catalonia.
The objective of this study was to investigate the prevalence and risk factors of
hepatitis A virus infection (HAV) in a sample of the adult population of
Catalonia in 2002 and to evaluate the changes with respect to a survey carried
out in 1996. METHODS: The prevalence of HAV antibodies was determined by a third 
generation competitive immunometric assay in a representative sample of 1292
people aged >15 years. The association between the prevalence and different
sociodemographic variables was determined by multiple logistic regression
analysis. RESULTS: The standardized global prevalence of HAV antibodies in 2002
was 68.2%, increased with age (p < 0.0001) and was associated with being born
outside Catalonia (OR: 1.75; 95% CI 1.11-2.76) and lower social class (OR: 1.14; 
95% CI 1.05-1.25). Compared with the last survey carried out in 1996 the
standardized global prevalence was lower (68.2% vs 77.8%; p < 0.0001) as was the 
prevalence in people under 45 years. CONCLUSION: The prevalence of the hepatitis 
A virus is decreasing in the adult population of Catalonia, especially in the
younger age groups. The programme of vaccination of adolescents begun in 1998 to 
control the disease can provide indirect protection to the unvaccinated
population.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17610736 [PubMed - indexed for MEDLINE]

120: Pediatrics. 2007 Jul;120(1):189-99.

Hepatitis A vaccine recommendations.

American Academy of Pediatrics Committee on Infectious Diseases.

Since licensure in 1995 of a hepatitis A vaccine, the Centers for Disease Control
and Prevention and the American Academy of Pediatrics have been implementing an
incremental hepatitis A immunization strategy for children. In 1996, children
living in populations with the highest rates of disease were targeted for
immunization, and in 1999 the program was expanded to immunization of children 2 
years and older living in states and counties with rates of hepatitis A that
historically have been higher than the national average. The 1999 program has
been successful; the current rate of hepatitis A is the lowest ever reported in
the United States. Regional, ethnic, and racial differences in the incidence of
hepatitis A have been eliminated. The incidence of hepatitis A in adults in
immunizing states has decreased significantly, suggesting a strong herd-immunity 
effect associated with immunization. In 2005, the US Food and Drug Administration
changed the youngest approved age of administration of hepatitis A vaccine from
24 to 12 months of age, which facilitated incorporation of the vaccine into the
recommended childhood immunization schedule. As the next step in the
implementation of the incremental vaccine immunization strategy, the American
Academy of Pediatrics now recommends routine administration of a Food and Drug
Administration-licensed hepatitis A vaccine to all children 12 to 23 months of
age in all states according to a Centers for Disease Control and
Prevention-approved immunization schedule. Available data suggest that hepatitis 
A vaccine can be coadministered with other childhood vaccines without decreasing 
immunogenicity. Hepatitis A vaccines have proven to be extremely safe. In
prelicensure clinical trials of both Havrix (GlaxoSmithKline, Rixensart, Belgium)
and Vaqta (Merck & Co Inc, Whitehouse Station, NJ), adverse events were uncommon 
and mild when they occurred, with resolution typically in less than 1 day.
Hepatitis A vaccine is contraindicated in people with a history of severe
allergic reaction to a previous dose of hepatitis A vaccine or to a vaccine
component. Because the hepatitis A vaccine is an inactivated product, no special 
precautions are needed for administration to people who are immunocompromised. No
data exist about administration of the hepatitis A vaccine to pregnant women, but
because it is not a live vaccine, the risk to mother and fetus should be
extremely low to nonexistent.

Publication Types: 
    Practice Guideline

PMID: 17606579 [PubMed - indexed for MEDLINE]

121: Prev Med. 2007 Nov;45(5):386-91. Epub 2007 May 21.

The shifting epidemiology of hepatitis A following routine childhood immunization
program in Israel.

Chodick G, Green MS, Heymann AD, Rosenmann L, Shalev V.

Medical Informatics Department, Maccabi Healthcare Services, Tel Aviv, Israel.
Hodik_g@mac.org.il

OBJECTIVES: In 1999 Israel became the first country to introduce immunization
against hepatitis A to its national childhood vaccination program. The study
objectives were to assess the uptake of hepatitis A vaccine following the new
policy and to examine the incidence of hepatitis A and the number of prevented
cases. METHODS: Data on incidence of hepatitis A and vaccination rates were
obtained from a large health maintenance organization in Israel covering 1.6
million members. We identified all members that were diagnosed by a primary care 
physician as suffering from hepatitis A, had a positive hepatitis A virus-IgM
test result, or were hospitalized due to hepatitis A between 1998 and 2004.
RESULTS: The results indicate that 5 years following its inclusion in the
national childhood immunization program, vaccination coverage levels with at
least one dose of hepatitis A vaccine for children aged under 5 years and 5-14
years were 87% and 51%, respectively. During this period the annual incidence
rates declined by 88% from 142.4 to 17.3 per 100,000. The most significant
reduction in morbidity was observed among children. CONCLUSIONS: In endemic
areas, vaccination of infants and children against hepatitis A may be efficient
to greatly reduce the total burden of the disease.

PMID: 17599401 [PubMed - indexed for MEDLINE]

122: J Korean Med Sci. 2007 Jun;22(3):546-8.

Incidence and seroprevalence of hepatitis A virus infections among young Korean
soldiers.

Kang CI, Choi CM, Park TS, Lee DJ, Oh MD, Choe KW.

Department of Internal Medicine, Armed Forces Capital Hospital, Seongnam, Korea.

This study was performed to determine the incidence and seroprevalence of
hepatitis A virus (HAV) infections in young soldiers in the Republic of Korea
Army. From January 2000 through December 2004, a total of 147 hepatitis A cases
were reported to the Armed Forces Medical Command. The annual incidence rates
were 7.4 per 100,000 persons in 2000, 1.6 in 2001, 4.4 in 2002, 9.8 in 2003, and 
6.2 in 2004, based on the reported cases among approximately 500,000 soldiers.
All patients were males with a median age of 21 yr (range, 19-27). The most
common symptom was nausea (86.5%), and all patients had recovered without
complications. In addition, in order to evaluate the seroprevalence of HAV
infection in young adults, serum samples were obtained from randomly selected
young subjects among those who had been admitted to the Armed Forces Capital
Hospital from September 2005 to February 2006. A total of 200 subjects were
enrolled in the study to analyze the anti-HAV immune status. The overall anti-HAV
IgG seropositive rate was 2% (4/200, 95% CI, 0.60-5.21%). Given the changing
epidemiology of the disease and the associated increase in morbidity, it was
suggested that routine HAV vaccination for Korean military personnel might be
necessary.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17596668 [PubMed - indexed for MEDLINE]

123: Hepatogastroenterology. 2007 Apr-May;54(75):871-7.

Genetic analysis of hepatitis A virus protein 2C in sera from patients with
fulminant and self-limited hepatitis A.

Fujiwara K, Yokosuka O, Imazeki F, Miki M, Suzuki K, Okita K, Tanaka E, Omat M.

Department of Medicine and Clinical Oncology, Graduate School of Medicine, Chiba 
University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.

BACKGROUND/AIMS: To examine whether genetic differences in hepatitis A virus
(HAV) are responsible for the range of clinical severities, we analyzed the HAV
2C genome, whose mutations have previously been shown to be important for
enhanced replication in cell culture systems and to be related to virulence in
simians. METHODOLOGY: Serum samples from 45 Japanese patients with sporadic
hepatitis A, comprising 9 patients with fulminant hepatitis (FH), 10 with severe 
acute hepatitis (AHs), and 26 with self-limited acute hepatitis (AH), were
examined for HAV RNA. RESULTS: Compared with the sequence of wild-type HAV strain
HM-175, the nucleotide sequences of 2C had homology of 89.0 +/- 0.6% in FH, 88.6 
+/- 0.9% in AHs, and 89.0 +/- 1.6% in AH. Differences were not statistically
significant among the three groups. Deduced amino acid sequences had homology of 
97.6 +/- 0.4% in FH, 96.5 +/- 1.9% in AHs, and 96.8 +/- 1.7% in AH. The
difference between FH and AH was statistically significant (p < 0.05), although
there were no specific nucleotide or amino acid substitutions. CONCLUSIONS:
Fulminant hepatitis patients had fewer amino acid substitutions in 2C, indicating
the association between severity of hepatitis A and amino acid variations in 2C
of HAV.

PMID: 17591082 [PubMed - indexed for MEDLINE]

124: Indian J Med Microbiol. 2007 Apr;25(2):137-9.

Hepatitis A vaccination in chronic liver disease: is it really required in a
tropical country like India?

Joshi N, Rao S, Kumar A, Patil S, Rani S.

Department of Gastroenterology, Nizam's Institute of Medical Sciences, Hyderabad 
- 500 082 Andhra Pradesh, India. nay_joshi @yahoo.com

Vaccination against hepatitis A virus (HAV) has been recommended in patients with
chronic liver disease to prevent any decompensation due to superinfection. This
may not hold good in high endemic areas for hepatitis A like India. The aim of
this study was to find out the seroprevalence of anti-HAV antibodies in patients 
with chronic liver disease and to justify the need for vaccination against
hepatitis A virus in these patients. One hundred and thirty three consecutive
patients with cirrhosis of liver attending Gastroenterology department of our
Institute between June 2004 and June 2005 were enrolled. Seventy-five healthy
persons were taken as controls. The diagnosis of cirrhosis was based on clinical 
profile, biochemical, radiological (ultrasound abdomen) and endoscopic findings. 
The etiology of cirrhosis was based on presence of viral markers, history of
significant alcohol consumption, autoimmune and metabolic workup. All patients
and controls were tested for antiHAV (total) antibodies using commercially
available enzyme-linked immunosorbent assay kits. Data from patients and control 
group were compared by unpaired 't' test and Chi square test. All subjects were
in the age group 11 to 75 years. Etiology of chronic liver disease was as
follows: HBV- 29.3%, HCV - 14.28%, HBV+HCV dual -1.5%, alcohol- 21.8%,
Cryptogenic -23.3%, Wilson"s Disease -1.5% and Budd chiari -1.5%. The prevalence 
of HAV was 93.2% in patients with cirrhosis of liver and 94.6% in controls. The
prevalence was almost similar irrespective of the etiology. In view of high
seroprevalence of HAV antibodies among cirrhotic patients in our study and the
high cost of the vaccine, the hepatitis A vaccination may not be routinely
required in this part of the world.

PMID: 17582184 [PubMed - indexed for MEDLINE]

125: J Comp Pathol. 2007 Jul;137 Suppl 1:S42-5. Epub 2007 Jun 6.

Vaccination of newborns against hepatitis A in the presence of maternally derived
antibodies.

Vidor E.

Sanofi Pasteur, Campus Mérieux, 1641 Avenue Marcel Mérieux, 69280 Marcy l'Etoile,
France. emmanuel.vidor@sanofipasteur.com

Infection by hepatitis A virus (HAV) is a significant cause of childhood disease 
but effective vaccines are available. Naturally acquired anti-HAV antibodies
ensure transfer of protective immunity which persists for up to 6 months in the
newborn. Such maternal anti-HAV antibodies are able to inhibit the antibody
responses in infants vaccinated with inactivated hepatitis A vaccines, although
no clinically significant consequences of this are observed. By increasing the
number of doses, for example by using a three dose primary vaccination schedule, 
and by increasing the amount of vaccinal antigen, this interfering effect may be 
partially overcome.

Publication Types: 
    Review

PMID: 17555761 [PubMed - indexed for MEDLINE]

126: Epidemiol Infect. 2008 Mar;136(3):406-9. Epub 2007 Jun 7.

Seroepidemiology of hepatitis A in voluntary blood donors from Pune, western
India (2002 and 2004-2005).

Gadgil PS, Fadnis RS, Joshi MS, Rao PS, Chitambar SD.

National Institute of Virology, Pune, India.

Recently, a changing pattern of hepatitis A epidemiology has been reported in the
Indian population indicating a rise in the rate of hepatitis A infection among
adults. The study's objective was to assess anti-HAV prevalence in voluntary
blood donors from middle and high socioeconomic strata. Serum samples collected
from voluntary blood donors from Pune city and its suburbs in the years 2002 and 
2004-2005 were tested for anti-HAV IgG antibodies. Serum samples collected during
2004-2005 were examined for anti-HAV IgM antibodies. Positive samples were tested
for HAV-RNA. Agewise anti-HAV positivity was significantly low in adults aged
18-25 years (90.4%) compared to those aged >25 years (97.4%) (P<0.01). A decline 
in anti-HAV prevalence was significant in 2004-2005 compared to that in 2002
(96.5% vs. 92.1%) (P<0.01). Overall, in both adult age groups, the proportion of 
anti-HAV positivity was remarkably low in the high socioeconomic group (HSG)
(88.96%) compared to that of the middle socioeconomic group (MSG) (95.86%)
(P<0.01). Anti-HAV IgM positivity was not significant (~1%), however, presence of
HAV-RNA in one of the samples indicated the possibility of horizontal
transmission of HAV. Increase in seronegativity to HAV in HSG implicates a rise
in the susceptible pool and indicates the need for vaccination against hepatitis 
A.

PMID: 17553176 [PubMed - indexed for MEDLINE]

127: Public Health Rep. 2007;122 Suppl 2:36-41.

Expansion of adult hepatitis A and B vaccination in STD clinics and other
settings in New York State.

Herlihy EJ, Klein SJ, Newcomb ML, Blog DS, Birkhead GS.

Immunization Program, New York State Department of Health, Albany, NY 12237, USA.
ejh04@health.state.ny.us

Since 1995, the New York State (NYS) Adult Hepatitis Vaccination Program has
promoted adult hepatitis B vaccination for those receiving sexually transmitted
disease (STD) clinic services. An average of 6,333 doses was administered
annually from 1995 to 1999. By 2000, only 15 of 57 county STD programs in NYS
outside of New York City participated. From 2000 to 2005, efforts to enroll
county health departments and others included outreach, provision of hepatitis A 
and B vaccine, materials and training, and new collaborations. All 57 counties
now participate. From 2000 to 2005, the number of settings offering hepatitis
vaccination increased from 57 to 119. Sites include STD clinics; jails; migrant, 
Indian health, and college health centers; and methadone clinics. More than
125,000 doses of hepatitis A and B vaccine were administered from 1995 through
2005, with annual increases up to a high of 21,025 doses in 2005. Intensive
promotion expanded hepatitis vaccination to all county STD clinics and other
settings where high-risk adults can be vaccinated.

PMID: 17542451 [PubMed - indexed for MEDLINE]

128: J Paediatr Child Health. 2007 May;43(5):383-7.

Epidemiology of severe hepatitis A in Indigenous Australian children.

MacIntyre CR, Burgess M, Isaacs D, McIntyre PB, Menzies R, Hull B.

National Centre for Immunisation Research and Surveillance of Vaccine Preventable
Diseases (NCIRS), The Children's Hospital at Westmead and the University of
Sydney, Sydney, NSW, Australia. rainam@chw.edu.au

AIMS: To describe the epidemiology of hepatitis A in Indigenous Australian
children. METHODS: Analysis and mapping of national notification and
hospitalisation data. RESULTS: Indigenous Australian children are at far higher
risk of clinical hepatitis A than their non-Indigenous counterparts, particularly
in the age group 0-4 years. Rates of hospitalisation (15.5 vs. 0.3 per 100,000)
and notification (24.4 vs. 1.8 per 100,000) were higher in Indigenous children
aged 0-4 years compared with other children in the same age group. In the age
group 5-14 years, the rates were 4.4 per 100,000 (Indigenous) versus 0.6 per
100,000 (non-Indigenous) hospitalisations. This excess morbidity falls sharply
with age. Rates were the highest in the Northern Territory, South Australia,
Western Australia and North Queensland. CONCLUSIONS: Indigenous children are at
risk of hepatitis A, particularly early in life. Mapping shows that rates were
the highest in jurisdictions with the largest Indigenous populations. This study 
presents baseline data against which to measure the success of new hepatitis A
vaccination programme for Indigenous Australian children which commenced in 2005.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17489829 [PubMed - indexed for MEDLINE]

129: Int J Hematol. 2007 Apr;85(3):191-4.

Reactive peripheral blood plasmacytosis in a patient with acute hepatitis A.

Wada T, Maeba H, Ikawa Y, Hashida Y, Okumura A, Shibata F, Tone Y, Inoue M,
Koizumi S, Takatori H, Sakai Y, Kaneko S, Yachie A.

Department of Pediatrics, Graduate School of Medical Science, Kanazawa
University, Kanazawa, Japan. taizo@ped.m.kanazawa-u.ac.jp

Reactive plasmacytosis is a transient expansion of plasma cell progenitors and
precursors. This rare condition has been reported to occur mainly in infections
and tumors. We describe a case of acute hepatitis A presenting with marked
peripheral blood plasmacytosis. Plasma cells made up 27.5% of the mononuclear
cells and had the immunophenotype CD10-CD19+CD20-CD21-CD23-CD34-CD38++HLA-DR+.
Although the level of interleukin 6 was not increased, the presence of activated 
T-cells with an inverted CD4/CD8 ratio and high levels of soluble interleukin 2
receptor and neopterin indicated a marked immune response to acute hepatitis A.
The patient's plasma cells had almost disappeared from the blood by hospital day 
16. This report may represent the first described case of reactive peripheral
blood plasmacytosis in acute hepatitis A.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't

PMID: 17483053 [PubMed - indexed for MEDLINE]

130: J Subst Abuse Treat. 2007 Jun;32(4):391-8. Epub 2006 Dec 12.

Integrating hepatitis prevention services into a substance use disorder clinic.

Hagedorn H, Dieperink E, Dingmann D, Durfee J, Ho SB, Isenhart C, Rettmann N,
Willenbring M.

Minneapolis Veterans Affairs Medical Center, Minneapolis, MN 55417, USA.
hildi.hagedorn@va.gov

The Healthy Liver Program, established at the Minneapolis Veterans Affairs
Medical Center Substance Use Disorder Clinic, provides screening for exposure to 
hepatitis infections, a group education class, and an individual nursing
appointment to review screening results, give vaccinations for hepatitis A and
hepatitis B, and make referrals to the hepatitis clinic as appropriate. A patient
chart audit was completed 11 months after the establishment of the Healthy Liver 
Program. The attendance rate for the educational group and individual feedback
sessions was 66.9%, with 94.1% of attendees accepting recommended hepatitis A
and/or hepatitis B vaccinations. All patients with chronic hepatitis C who
attended the Healthy Liver Program received a referral for evaluation in the
hepatitis clinic, as compared with only 50% of patients with chronic hepatitis C 
who were identified before the establishment of the program. The importance of
providing comprehensive educational sessions and recommendations for how patients
with substance use disorders can access hepatitis screening, vaccination, and
treatment resources are stressed.

Publication Types: 
    Research Support, U.S. Gov't, Non-P.H.S.

PMID: 17481462 [PubMed - indexed for MEDLINE]

131: J Med Virol. 2007 Jun;79(6):657-62.

Molecular epidemiology of hepatitis A in St. Petersburg, Russia, 1997-2003.

Davidkin I, Zheleznova N, Jokinen S, Gorchakova O, Broman M, Mukomolov S.

National Public Health Institute, Helsinki, Finland. irja.davidkin@ktl.fi

The molecular epidemiology of hepatitis A virus (HAV) strains circulating in the 
St. Petersburg and Karelia regions was studied during 1997-2003. Hepatitis A
virus RNA was isolated from both clinical samples (stools or sera) and
environmental samples (sewage water). RT-PCR was carried out using different
primer pairs from the VP1/2A and VP1 genomic regions, the variable parts of the
HAV genome. PCR products were sequenced and 306 nucleotides from the VP1/2A and
332 nucleotides from the VP1 region were used for phylogenetic analysis. The
results show that the IA subtype was the most common during the follow-up period:
>90% of the isolated HAV strains belonged to that subtype. The HAV strains found 
in intravenous drug users belonged to subtypes IA and IIIA. Only one out of a
total of 88 sequenced strains was of the IB subtype. The subtypes IB and IIIA
were found only in 2001-2003, which suggests that new strains were introduced
into the endemic situation. The results indicate the usefulness of molecular
epidemiological methods in studying changes in the circulating HAV strains and in
tracing transmission routes. (c) 2007 Wiley-Liss, Inc.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17457910 [PubMed - indexed for MEDLINE]

132: J Korean Med Sci. 2007 Apr;22(2):218-22.

Emerging need for vaccination against hepatitis A virus in patients with chronic 
liver disease in Korea.

Song HJ, Kim TH, Song JH, Oh HJ, Ryu KH, Yeom HJ, Kim SE, Jung HK, Shim KN, Jung 
SA, Yoo K, Moon IH, Chung KW.

Department of Internal Medicine, Ewha Medical Research Institute, Ewha Womans
University College of Medicine, Seoul, Korea.

Vaccination against hepatitis A virus (HAV) is recommended for patients with
chronic liver disease (CLD), but this has been deemed unnecessary in Korea since 
the immunity against HAV was almost universal in adults. However, this practice
has never been reevaluated with respect to the changing incidence of adult acute 
hepatitis A. We retrospectively reviewed the medical records of 278 patients with
acute hepatitis A diagnosed from January 1995 to November 2005 and prospectively 
tested 419 consecutive CLD patients from July to December 2005 for the presence
of IgG anti-HAV. The number of patients with acute hepatitis A has markedly
increased recently, and the proportion of adult patients older than 30 yr has
been growing from 15.2% during 1995-1999, to 28.4% during 2000-2005 (p=0.019).
Among 419 CLD patients, the seroprevalences of IgG anti-HAV were 23.1% for those 
between 26 and 30 yr, 64% between 31 and 35 yr, and 85.0% between 36 and 40 yr.
These data demonstrate that immunity against HAV is no more universal in adult
and substantial proportion of adult CLD patients are now at risk of HAV infection
in Korea. Therefore, further study on seeking proper strategy of active
immunization against HAV is warranted in these populations.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 17449927 [PubMed - indexed for MEDLINE]

133: Travel Med Infect Dis. 2007 May;5(3):171-5. Epub 2006 Sep 20.

Ten-year antibody persistence induced by hepatitis A and B vaccine (Twinrix) in
adults.

Van Herck K, Leroux-Roels G, Van Damme P, Srinivasa K, Hoet B.

Centre for the Evaluation of Vaccination, WHO Collaborating Centre for Prevention
and Control of Viral Hepatitis, Unit of Epidemiology and Social Medicine,
University of Antwerp - Campus Drie Eiken, Wilrijk, Belgium.
koen.vanherck@ua.ac.be

BACKGROUND: Hepatitis A and B infections are prevalent worldwide and cause
significant morbidity and mortality. A combined vaccine providing dual protection
against hepatitis A and B is available (Twinrix, GlaxoSmithKline Biologicals).
METHOD: Two cohorts of adults aged 17-43 years were vaccinated with Twinrix
according to a 0, 1, 6 months schedule and followed up for 10 years. RESULTS: One
month after the primary vaccination course (Month 7), all subjects were
seropositive for anti-HAV and all had anti-HBs> or = 10 mIU/ml. At month 120,
100% of subjects (N=34; N=29) in both cohorts were seropositive for anti-HAV;
94.1% and 86.2% of subjects had anti-HBs > or = 10 mIU/ml. The geometric mean
concentrations (GMC; mIU/ml) were 373.9 and 674.6 in the two cohorts for
anti-HAV, and 103.8 and 320.0, respectively, for anti-HBs. None of the serious
adverse events reported throughout the follow-up period were considered by the
investigator to be causally related to vaccination. CONCLUSIONS: Combined
hepatitis A and B vaccine, Twinrix, is safe, well-tolerated and has demonstrated 
a highly immunogenic profile. Persistence of anti-HAV and anti-HBs antibodies in 
adults remains high for at least 10 years after primary vaccination.

Publication Types: 
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 17448944 [PubMed - indexed for MEDLINE]

134: Epidemiol Infect. 2008 Mar;136(3):334-40. Epub 2007 Apr 20.

Use of sensitivity analysis to assess the effects on anti-hepatitis A virus
antibodies of access to household water supply.

Cabral MD, Luiz RR.

Brazilian Institute of Geography and Statistics, IBGE, Rio de Janeiro, Brazil.
maria.cabral@ibge.gov.br

The objective of this study was to assess the impact of a possible unmeasured
confounding variable in a previously published association between the effects of
household water supply and positive results for hepatitis A serology. This was
estimated using a path of integration between two methods of sensitivity
analysis, called Rosenbaum's method and Greenland's external adjustment. The
association between household water supply and positive results for hepatitis A
(outcome) serology was insensitive to confounding unless the odds ratio for the
association between the confounder and the outcome was > or = 4. The integration 
of the two sensitivity analysis methods presented proved useful when assessing
the effects of a potential unmeasured confounder.

Publication Types: 
    Evaluation Studies

PMID: 17445315 [PubMed - indexed for MEDLINE]

135: Pediatr Int. 2007 Apr;49(2):215-9.

Lipid profile in children with acute viral hepatitis A.

Selimoglu MA, Caner I, Yildiz L.

Department of Pediatric Gastroenterology, Hepatology and Nutrition, Faculty of
Medicine, Atatürk University, Erzurum, Turkey. ayseselimoglu@hotmail.com

BACKGROUND: Most of the knowledge about lipid parameters in acute hepatitis is
originated from adult studies. In this study, the authors investigated lipid
profile of children with acute hepatitis A (AVH) at diagnosis and recovery in
order to observe the behavior of lipid parameters in such children. METHODS: A
total of 28 children (mean age, 8.2 +/- 2.7 years) with AVH and 20 gender and
age-matched healthy children were included. In addition to the routine tests,
triglyceride, cholesterol, low-density lipoprotein (LDL), high-density
lipoprotein (HDL), plasma apo A-I and apo B were studied at diagnosis and
recovery. RESULTS: Serum triglyceride and apo B level was higher, and apo A-I
level was lower in patients compared to healthy children (P < 0.01, <0.05 and
<0.01, respectively). On admission, three children had fulminant hepatic failure 
(FHF). Serum lipid parameters were evaluated in respect with the presence of
icterus and FHF, and found that apo A-I level was lower in icteric children and
LDL and apo A-I were lower in FHF compared to others (P < 0.05, P < 0.01 and P < 
0.05, respectively). At recovery, while triglyceride, cholesterol, LDL, and apo B
decreased (P < 0.01), HDL and apo A-I increased (P < 0.01). Serum apo A-I level
was inversely correlated with serum ammonia level but was positively correlated
with serum albumin (P < 0.05). CONCLUSIONS: It was shown that serum triglyceride 
and apo B level increased, but apo A-I level decreased in patients with AVH.
While cholestasis lowers apo A-I level, severe hepatic damage lowers both apo A-I
and LDL. These parameters return to normal levels within 30 days. An interesting 
relationship between ammonia and apo A-I deserves further investigations,
speculatively focused on hepatocyte nuclear factor 4 alpha.

PMID: 17445041 [PubMed - indexed for MEDLINE]

136: BMC Infect Dis. 2007 Apr 18;7:31.

Trends of hepatitis A hospitalization and risk factors in Quebec, Canada, between
1990 and 2003.

Canuel M, De Serres G, Duval B, Gilca R, De Wals P, Gilca V.

Department of Social and Preventive Medicine, Laval University, Quebec, Canada.
magalie.canuel@inspq.qc.ca <magalie.canuel@inspq.qc.ca>

BACKGROUND: In Canada, targeted vaccination of at risk groups for hepatitis A
(HA) is done since the mid 1990s resulting in declining incidence. This study
estimated the year and age specific hospitalization rates and distribution of
risk factors for HA in Quebec, Canada, between 1990 and 2003. METHODS: Records of
patients hospitalized with HA-related diagnostic codes were retrieved from the
provincial database. Hospital charts of all deceased cases and a random sample of
all other records were reviewed. RESULTS: From 1503 hospitalization records, 573 
charts were reviewed including 49 (91%) of the 54 deceased patients. Confirmed
acute HA was present in 79% of records where HA was the primary diagnosis, and in
3%-8% of records where HA was a secondary diagnosis. From the total estimated
number of hospitalizations, 96% had HA as the primary diagnosis. The
hospitalization rate decreased from 1.06 per 100 000 person-years between 1990
and 1997 to 0.36 between 1998 and 2003. During the study period, 54% HA
hospitalizations were in 20-39 year-olds. The overall case fatality ratio among
hospitalized patients was 1.4%, increasing from 0.4% in those < 40 years old to
12.5% in those > or =60 years. By decreasing order, reported risk factors were
travel to HA endemic countries (30%), MSM (18%) and household contacts (11%).
CONCLUSION: HA hospitalization rates have been low since 1998 but the cause of
this is unclear given the cyclical pattern of HA. Travel to endemic countries
remains the most important risk factor and improved control of HA will require
better strategies to vaccinate travelers.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17442107 [PubMed - indexed for MEDLINE]

137: Clin Infect Dis. 2007 May 1;44(9):e73-7. Epub 2007 Mar 28.

Acute hepatitis with severe cholestasis and prolonged clinical course due to
hepatitis A virus Ia and Ib coinfection.

Coppola N, Genovese D, Pisaturo M, Taffon S, Argentini C, Pasquale G, Sagnelli C,
Piccinino F, Rapicetta M, Sagnelli E.

Department of Public Medicine, Section of Infectious Diseases, Second University 
of Naples, Naples, Italy.

BACKGROUND: Acute viral hepatitis due to hepatitis A virus is a self-limited
illness that infrequently has a severe clinical course. METHODS: We analyzed the 
virological characteristics of acute hepatitis A in a patient with a severe
clinical presentation (peak total and conjugated bilirubin levels, 65.5 mg/dL and
40.1 mg/dL, respectively) and a course of disease that lasted 7 months. RESULTS: 
Hepatitis A virus sequencing revealed coinfection with 2 subgenotypes of
hepatitis A virus (Ia and Ib) as etiological factors of the illness. CONCLUSIONS:
Hepatitis A virus Ia and Ib coinfection may have accounted for the prolonged and 
severe course of illness.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't

PMID: 17407028 [PubMed - indexed for MEDLINE]

138: Virus Genes. 2007 Oct;35(2):155-9. Epub 2007 Mar 29.

Genetic analysis of HAV strains in Tunisia reveals two new antigenic variants.

Gharbi-Khelifi H, Sdiri K, Harrath R, Fki L, Hakim H, Berthomé M, Billaudel S,
Ferre V, Aouni M.

Laboratoire des Maladies Transmissibles et Substances Biologiquement Actives,
Faculté de Pharmacie de Monastir, Rue Avicenne, 5000 Monastir, Tunisia.
khelifi_hakima@yahoo.fr

To evaluate the genetic variability of hepatitis A virus (HAV) isolates in
Tunisia, serum samples were collected from 99 patients in different Tunisian
areas in 2003 containing 92 cases with acute hepatitis, five with severe acute
hepatitis and two with fulminant hepatitis. The entire VP1 gene was amplified and
sequenced. Sequences were then aligned and a phylogenetic analysis was performed.
Additionally, the amino acid (aa) sequence of the VP1 was determined. The
analysis of Tunisian HAV isolates revealed that all the isolates were
sub-genotype IA with 96.4%-99.8% of identity and showed the emergence of two
novel antigenic variants. The Tun31-03 antigenic variant, with a 38 aa deletion
containing Met156, Val171, Leu174 and Ala176 and located between 150 and 187 aa
of the VP1 protein where neutralization escape mutations, was found. The second
antigenic variant, Tun36-03, was isolated from a patient with fulminant hepatitis
and presented a substitution of Thr by Pro at position 10 of the VP1 protein.
This amino acid is located in a peptide presenting an antigenically reactive
epitope of the VP1 protein. This substitution has never been described
previously.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17393293 [PubMed - indexed for MEDLINE]

139: Rev Gastroenterol Disord. 2007 Winter;7(1):1-21.

The A's and B's of vaccine-preventable hepatitis: improving prevention in
high-risk adults.

Oldfield EC 3rd, Keeffe EB.

Division of Infectious Diseases, Department of Medicine, Eastern Virginia Medical
School, Norfolk, Virginia, USA.

Acute hepatitis A and acute hepatitis B are associated with significant
morbidity, time away from work or usual activities, substantial cost to the
healthcare system, and some mortality. Despite the availability of vaccines
against hepatitis B and hepatitis A since 1981 and 1995, respectively, and a
combined hepatitis A and B vaccine since 2001, immunization rates against these
vaccine-preventable diseases are appallingly low. In particular, several groups
of adults, such as men who have sex with men, heterosexuals with multiple
partners, injection drug users, persons with human immunodeficiency virus
infection, travelers to endemic areas, and persons with chronic liver disease,
are at particularly high risk for acute hepatitis A and B or for a more severe
illness or a higher rate of chronicity in the case of hepatitis B. Studies have
confirmed that hepatitis A and hepatitis B vaccines are safe and immunogenic in
patients in these populations, although patients with more advanced disease may
respond less well. These observations have led to the recommendation that
patients falling into the above risk groups undergo hepatitis A and B vaccination
early in the natural history of their underlying risk behavior or diseases.
Vaccination rates are low in clinical practice, and public health and educational
programs are needed to overcome barriers to facilitate timely implementation of
these recommendations. The use of a combined vaccination, possibly using an
accelerated administration schedule, provides convenience and may increase
compliance.

Publication Types: 
    Review

PMID: 17392626 [PubMed - indexed for MEDLINE]

140: J Med Virol. 2007 May;79(5):483-7.

Molecular epidemiology of hepatitis A virus in a group of Portuguese citizens
living in Lisbon area.

Rodrigues L, Pista A, Oliveira A, Agua-Doce I, Manita C, Paixão MT.

Hepatitis Unit, Centre of Virology, National Institute of Health, Lisboa,
Portugal. luisa.rodrigues@insa.min-saude.pt

Hepatitis A virus (HAV) is the most important cause of acute infectious hepatitis
worldwide. In Portugal, due to improvements in sanitation epidemic outbreaks of
HAV infection have become less frequent. This report is the first, to our
knowledge that characterized HAV in Portugal. For the detection and molecular
characterization of HAV cases in a group of Portuguese individuals in the Lisbon 
area, 31 serum samples were tested: 8 from symptomatic children from an acute
hepatitis A outbreak in a Roma (Gipsies) community (2004-2005), and 22 from
patients with acute HAV from sporadic cases (2005-2006). A sample of CSF involved
in a case of meningitis was also included. IgM anti-HAV detection and nested
reverse transcription (RT-PCR), with primers located at the VP1-P2a region, was
undertaken to detect HAV genome. In positive samples, molecular characterization 
was followed by phylogenetic analysis. All samples (n = 31) were positive for IgM
anti-HAV. HAV RNA was found in 96.7% of cases. All isolates were classified as
genotype I: 22 belonged to sub-genotype IA (73.3%), and 8 to sub-genotype IB
(26.7%). All strains obtained from an acute HAV outbreak had sub-genotype IA, in 
which seven isolates (87.5%) had identical sequences. In HAV sporadic cases
sub-genotypes IA and IB were identified, and this may reflect the co-circulation 
of these two sub-genotypes in Portugal. Molecular epidemiology of HAV infection
in this group of Portuguese appears to be similar to other European countries.
HAV phylogenetic studies can provide important information for the design of
appropriate public health measures.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17387747 [PubMed - indexed for MEDLINE]

141: J Med Virol. 2007 May;79(5):488-94.

Different transmission patterns of hepatitis A virus for two main risk groups as 
evidenced by molecular cluster analysis.

Tjon G, Xiridou M, Coutinho R, Bruisten S.

Municipal Health Service Amsterdam, Amsterdam, The Netherlands.

Men who have sex with men and traveling children are the most important risk
groups for transmission of hepatitis A virus (HAV) in Amsterdam, The Netherlands.
Between these two risk groups, different HAV genotypes are found. In this study
the patterns of introduction and transmission of HAV were investigated in the two
groups. HAV sequences from Amsterdam patients were divided according to risk: (I)
travelers and their contacts, (II) homosexual men and their contacts. The
sequences in each risk group were then grouped into clusters based on the genetic
distances between the sequences. Among travelers many sporadic cases were found, 
the clusters were small, and introduced frequently into the population, mostly in
the second half of each calendar year, indicating a seasonal pattern of
introduction and transmission after the summer holidays. Among men who have sex
with men the clusters were bigger and remained present for a longer time;
sporadic cases were few, and introduction of new strains occurred only
occasionally but throughout the year. Our findings indicate that new HAV strains 
are frequently imported into Amsterdam by travelers, but they are limited in the 
extent and season of their spread. In contrast, HAV is only occasionally imported
into the male homosexual and bisexual population, but remains endemic and spreads
to a large number of individuals without a seasonal pattern.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17385681 [PubMed - indexed for MEDLINE]

142: Virus Res. 2007 Jun;126(1-2):116-27. Epub 2007 Mar 21.

Full-length sequences of subgenotype IIIA and IIIB hepatitis A virus isolates:
characterization of genotype III HAV genomes.

Endo K, Takahashi M, Masuko K, Inoue K, Akahane Y, Okamoto H.

Division of Virology, Department of Infection and Immunity, Jichi Medical
University School of Medicine, 3311-1 Yakushiji, Shimotsuke-Shi, Tochigi-Ken
329-0498, Japan.

To elucidate the extent of genomic heterogeneity of human hepatitis A virus (HAV)
strains and to characterize genotype III HAV strains over the entire genome, the 
full-length sequence of three subgenotype IIIA isolates (HA-JNG04-90F,
HA-JNG08-92F, and HAJ95-8F) and one IIIB isolate (HAJ85-1F) was determined. The
HA-JNG04-90F, HA-JNG08-92F, and HAJ95-8F genomes which comprised 7463 or 7464 nt 
excluding the poly(A) tail, were closest to a reported nearly entire sequence of 
a IIIA isolate (NOR-21) with identities of 94.4-97.8% over the entire ORF
sequence, and the HAJ85-1 genome (7462 nt) to HA-JNG06-90F of IIIB with an
identity of 98.6%. The phylogenetic trees constructed based on the complete ORF
sequence or the 168-nt VP1/2A junction sequence and comparative analysis with
reported HAV isolates suggested the presence of three distinct clusters within
IIIA represented by HA-JNG04-90F, HA-JNG08-92F, and HAJ95-8F. The extreme 5' end 
sequences of IIIA and IIIB were well-conserved, beginning with the sequence
UUCAAGAGGG. A single base deletion of G at nt 20, which is involved in the
formation of a small loop in domain I, was characteristic of both IIIA and IIIB. 
Conserved and divergent amino acid sequences as well as amino acids unique to
genotype III, IIIA or IIIB were recognized.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17376556 [PubMed - indexed for MEDLINE]

143: Emerg Infect Dis. 2007 Jan;13(1):156-8.

Major outbreak of hepatitis A associated with orange juice among tourists, Egypt,
2004.

Frank C, Walter J, Muehlen M, Jansen A, van Treeck U, Hauri AM, Zoellner I, Rakha
M, Hoehne M, Hamouda O, Schreier E, Stark K.

Robert Koch Institute, Berlin, Germany. FrankC@RKI.de

In 2004, a major outbreak of hepatitis A among tourists returning from Egypt
involved 351 case-patients from 9 European countries who were infected with a
single strain (genotype 1 b). The case-control study identified orange juice as
the most likely infection vehicle. Vaccination against hepatitis A virus is
strongly recommended before travel to disease-endemic areas.

PMID: 17370535 [PubMed - indexed for MEDLINE]

144: Eur J Epidemiol. 2007;22(3):195-202. Epub 2007 Mar 14.

A population-based prevalence study of hepatitis A, B and C virus using oral
fluid in Flanders, Belgium.

Quoilin S, Hutse V, Vandenberghe H, Claeys F, Verhaegen E, De Cock L, Van Loock
F, Top G, Van Damme P, Vranckx R, Van Oyen H.

Unit of Epidemiology, Scientific Institute of Public Health, Juliette
Wytsmanstreet 14, 1050 Brussels, Belgium. Sophie.quoilin@iph.fgov.be

Ten years after the first seroprevalence study performed in Flanders, the aim of 
this cross sectional study was to follow the evolution of hepatitis A, B and C
prevalence. The prevalence of hepatitis A antibodies, hepatitis B surface antigen
and hepatitis C antibodies was measured in oral fluid samples collected by postal
survey. Using the National Population Register, an incremental sampling plan was 
developed to obtain a representative sampling of the general population. A total 
of 24,000 persons were selected and 6,000 persons among them contacted in a first
wave. With 1834 participants a response rate of 30.6% was achieved. The
prevalence was weighted for age and was 20.2% (95% CI 19.43-21.08) for hepatitis 
A, 0.66% (95% CI 0.51-0.84) for hepatitis B surface antigen and 0.12% (95% CI
0.09-0.39) for hepatitis C. The prevalence of hepatitis A and C in the Flemish
population is lower in 2003 compared with the results of the study performed in
1993. The difference may be due to a real decrease of the diseases but also to
differences in the methodology. The prevalence of hepatitis B surface antigen
remains stable. Considering the 30% response rate and the high quality of the
self-collected samples as reflect of a good participation of the general
population, saliva test for prevalence study is a good epidemiological monitoring
tool.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17356926 [PubMed - indexed for MEDLINE]

145: Epidemiol Infect. 2008 Jan;136(1):10-3.

Protecting contacts of hepatitis A: what's the difference between vaccine and
human normal immunoglobulin?

Crowcroft NS.

Immunisation Department, Health Protection Agency Centre for Infections, London, 
UK. natasha.crowcroft@hpa.org.uk

The efficacy of vaccine when time since exposure is prolonged (more than 1 week
from onset of illness in the index case) is unknown, but is likely to be
significantly lower than human normal immunoglobulin (HNIG). We estimated the
number of additional secondary cases that may occur through giving vaccine
instead of HNIG to contacts of cases of hepatitis A who are identified more than 
1 week after onset in the index case. This was calculated for different levels of
vaccine efficacy, assuming HNIG efficacy to be 80-90%. The number of households
that need to be treated to prevent one secondary case was calculated using
estimates of secondary attack ratios (AR). If more than 1 week has elapsed from
onset of illness in the index case, for an average household size of 2.3 people, 
a vaccine efficacy of 50% and an AR of 10-25%, 8-26 households would need to be
treated with vaccine before one additional secondary case would be observed. As
UK public health professionals manage around one hepatitis A case per month, it
would take from 8 months to over 2 years for them to observe one additional case 
amongst contacts using vaccine rather than HNIG. It is unlikely that an average
practitioner would notice if vaccine were 30% less effective than HNIG. Public
health practice and advice to patients and contacts should be based on evidence
as well as experience.

PMID: 17352837 [PubMed - indexed for MEDLINE]

146: J Gastroenterol. 2007 Feb;42(2):152-60. Epub 2007 Mar 12.

The cost-effectiveness of universal vaccination of children against hepatitis A
in Argentina: results of a dynamic health-economic analysis.

Lopez E, Debbag R, Coudeville L, Baron-Papillon F, Armoni J.

Hospital Guttierez, Buenos Aires, Argentina.

BACKGROUND: Socioeconomic improvements can reduce levels of endemic hepatitis A, 
but conversely increase the burden of disease. Routine childhood vaccination can 
rapidly control hepatitis A infection rates through the induction of herd
immunity, although such programs can be costly. METHODS: We evaluated the
healthcare benefits and cost-effectiveness of a routine childhood vaccination
program against hepatitis A in Argentina, using a dynamic model that incorporated
the changing epidemiology of infection and the impact of vaccine-induced herd
immunity. Demographic, disease, and economic data from Argentina were used where 
available. RESULTS: At 95% coverage, the program would reduce the number of
hepatitis A infections by 352,405 annually, avoiding 121,587 symptomatic cases
and 428 deaths. Substantial healthcare benefits were also observed with
vaccination coverage as low as 70%, which would prevent 295,826 infections.
Economically, the program would save 23,989,963 US$ annually at 95% coverage,
equivalent to 3,429 US$ per life-year gained. The program remained cost-saving in
response to variation in factors, including disease-related costs, discount rate,
herd immunity level, and rate of decrease of force of infection. The break-even
cost per vaccine dose for the society was 25 US$ in the base-case, more than
three times the current public cost of 7 US$ per dose. CONCLUSIONS: Routine
childhood vaccination against hepatitis A showed both health benefits and robust 
economic benefits in this analysis, supporting the recent decision of the
Argentine government to implement such a program.

PMID: 17351805 [PubMed - indexed for MEDLINE]

147: Virus Res. 2007 Aug;127(2):151-7. Epub 2007 Feb 27.

Genetic variability and molecular evolution of hepatitis A virus.

Cristina J, Costa-Mattioli M.

Laboratorio de Virología Molecular, Centro de Investigaciones Nucleares, Facultad
de Ciencias, Iguá 4225, 11400 Montevideo, Uruguay. cristina@cin.edu.uy

Hepatitis A virus (HAV), the causative agent of type A viral hepatitis, was first
identified about three decades ago. Recent findings have shown that HAV possess
several characteristics that make it unique among the family Picornaviridae,
particularly in terms of its mechanisms of polyprotein processing and virion
morphogenesis. HAV circulates in vivo as distributions of closely genetically
related variants referred to as quasispecies. HAV exploits all known mechanisms
of genetic variation to ensure its survival, including mutation and
recombination. Only one serotype and six different genetic groups (three humans
and three simian) have been described. HAV mutation rate is significantly lower
as compared to other members of the family Picornaviridae. The mode of evolution 
appears, at least in part, to contribute to the presence of only one known
serotype.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 17328982 [PubMed - indexed for MEDLINE]

148: J Med Virol. 2007 Apr;79(4):356-65.

Molecular epidemiological studies show that hepatitis A virus is endemic among
active homosexual men in Europe.

Stene-Johansen K, Tjon G, Schreier E, Bremer V, Bruisten S, Ngui SL, King M,
Pinto RM, Aragonès L, Mazick A, Corbet S, Sundqvist L, Blystad H, Norder H, Skaug
K.

Division of Infectious Disease Control, Norwegian Institute of Public Health,
Oslo, Norway. kasj@fhi.no

Large outbreaks of hepatitis A have occurred in Denmark, Germany, the
Netherlands, Norway, Spain, Sweden, and the United Kingdom during the period
1997-2005 affecting homosexual men. A collaborative study was undertaken between 
these countries to determine if the strains involved in these hepatitis A
outbreaks were related genetically. The N-terminal region of VP1 and the VP1/P2A 
region of the strains were sequenced and compared. The majority of the strains
found among homosexual men from the different European countries formed a closely
related cluster, named MSM1, belonging to genotype IA. Different HAV strains
circulated among other risk groups in these countries during the same period,
indicating that specific strains were circulating among homosexual men
exclusively. Similar strains found among homosexual men from 1997 to 2005
indicate that these HAV strains have been circulating among homosexual men for a 
long time. The homosexual communities are probably too small within the
individual countries to maintain HAV in their population over time, whereas the
homosexual communities across Europe are probably sufficiently large to sustain
continued circulation of homologous HAV strains for years resulting in an endemic
situation among homosexual men. (c) 2007 Wiley-Liss, Inc.

PMID: 17311331 [PubMed - indexed for MEDLINE]

149: Microbiol Immunol. 2007;51(2):185-91.

Shifting seroepidemiology of hepatitis A in Japan, 1973-2003.

Kiyohara T, Sato T, Totsuka A, Miyamura T, Ito T, Yoneyama T.

Department of Virology II, National Institute of Infectious Diseases,
Musashi-murayama, Tokyo, Japan. kiyohara@nih.go.jp

BACKGROUND: Hepatitis A infection is caused by hepatitis A virus (HAV) contracted
through fecal-oral transmission. Life-long immunity is conferred after infection.
Improved sanitary conditions have generally resulted in a significant decline in 
the incidence of hepatitis A. However, a low incidence of infection results in
increased HAV susceptibility. The present study investigates the prevalence of
anti-HAV antibody and clarifies the current HAV status and HAV susceptibility in 
Japan at 2003. METHODS: A total of 2,430 serum specimens collected during 2003
from Japanese individuals ranging in age from 0-92 years, were tested for
anti-HAV antibody using an inhibition enzyme linked immunosorbent assay. All
specimens were obtained from the WHO and the National Serum Reference
Bank/National Institute of Infectious Diseases, Tokyo, Japan. RESULTS: The
overall seroprevalence was 12.2%. Anti-HAV antibodies were rarely detected in
individuals between 0-44 years of age. Starting from the age of 45-49 years,
seropositivity gradually increased through age 65 years and above. Seroprevalence
was not affected by gender, and geographic distribution did not affect
age-specific seroprevalence until the age of 60 years. CONCLUSIONS: HAV
susceptibility in Japan is increasing annually. Particularly, the prevalence of
anti-HAV antibody in individuals older than 50 years in 2003 was 50.3%, which is 
significantly lower than that of corresponding studies in 1994 (74.3%), 1984
(96.9%) and 1973 (96.9%). The growing susceptible population of advanced age
results in more frequent HAV infection among them. The surveillance of anti-HAV
antibody prevalence is useful for implementing preventive measures and for
controlling the spread of HAV.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17310086 [PubMed - indexed for MEDLINE]

150: Expert Opin Biol Ther. 2007 Mar;7(3):379-89.

Twinrix vaccination schedules among injecting drug users.

Brim N, Zaller N, Taylor LE, Feller E.

Brown Medical School, Providence, Rhode Island, USA, 2The Miriam Hospital, 164
Summit Ave, Providence, RI 02906, USA. nzaller@lifespan.org

Twinrix is the only licensed vaccine that provides dual protection against
infection with hepatitis A virus (HAV) and hepatitis B virus (HBV). The standard 
vaccination schedule for Twinrix is 0, 1 and 6 months. However, many high-risk
populations, such as injecting drug users (IDUs), do not complete the vaccination
series and, thus, do not acquire sufficient immunity against HAV and HBV. Twinrix
can be administered using an accelerated vaccination schedule of 0, 7 and 21
days, with a booster recommended at 12 months. This manuscript reviews the
available literature on vaccinating IDUs against HAV and HBV. The authors
conclude that there is insufficient evidence regarding whether the accelerated
Twinrix HAV/HBV vaccination schedule would yield a greater number of IDUs
protected against both HAV and HBV.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, U.S. Gov't, P.H.S.

PMID: 17309329 [PubMed - indexed for MEDLINE]

151: Vaccine. 2007 May 4;25(18):3581-7. Epub 2007 Jan 25.

Impact of hepatitis A vaccination on health care utilization in the United
States, 1996-2004.

Zhou F, Shefer A, Weinbaum C, McCauley M, Kong Y.

National Center for Immunization and Respiratory Diseases (NCIRD), Centers for
Disease Control and Prevention (CDC), Atlanta, GA 30333, United States.
faz1@cdc.gov

BACKGROUND: Since 1996, hepatitis A vaccine has been recommended for persons at
risk for infection and children living in communities with the highest disease
rates. In 1999, this recommendation was expanded to include all children in 17
states with high incidence compared to a national baseline period. Reported
hepatitis A incidence has decreased substantially since 1999; however,
comprehensive data on changes in hospital and outpatient utilization have not
been reported. OBJECTIVE: To analyze a health insurance claims database to
examine impacts of the hepatitis A vaccination program on medical visits and
associated expenditures. METHODS: We conducted a retrospective study of the
1996-2004 Medstat MarketScan databases, which include enrollees of more than 100 
health insurance plans offered by approximately 40 large employers each year,
using 1996 and 1997 as the pre-vaccination baseline. Trends in rates of medical
care visits were analyzed using Poisson regression method. RESULTS: From the
pre-vaccination era to 2004, hospitalizations due to hepatitis A declined by
68.5% (from 0.81 to 0.26 per 100,000 population, P<0.001) and ambulatory visits
declined by 41.5% (from 12.9 to 7.5 per 100,000 population, P<0.001). Ambulatory 
visits declined in all age groups, with the greatest declines among children<18
years old. Declines were greater among enrollees who resided in the 17
vaccinating states (58.5%) than those in non-vaccinating states (32.7%, P<0.001).
After adjusting to the US population, using data derived from a privately insured
population, total estimated direct medical expenditures for hepatitis A-related
hospitalizations and ambulatory visits declined by 68.1%, from an average of
$29.1 million in 1996 and 1997 to $9.3 million in 2004. CONCLUSIONS: Since the
introduction of the hepatitis A vaccination program, hospitalizations, ambulatory
visits, and their associated expenditures due to hepatitis A disease have
declined substantially among all age groups across the US. Greater declines were 
seen in the 17 states with vaccination recommendations for hepatitis A.

PMID: 17306908 [PubMed - indexed for MEDLINE]

152: J Viral Hepat. 2007 Mar;14(3):189-93.

Predictors of immunity after hepatitis A vaccination in HIV-infected persons.

Overton ET, Nurutdinova D, Sungkanuparph S, Seyfried W, Groger RK, Powderly WG.

Washington University School of Medicine, St Louis, MO, USA.
toverton@im.wustl.edu

Hepatitis A virus (HAV) infection remains a health risk for human
immunodeficiency virus (HIV)-infected persons. While the inactivated HAV vaccine 
affords protection to immunocompetent persons >95% of the time, rates of
developing protective antibody (anti-HAV) in HIV+ persons are considerably lower.
Although low CD4+ T-cell counts have previously been reported to be correlated
with this poor response, the effect of HIV viraemia on HAV vaccine response has
not previously been reported. The medical records of HIV-infected patients who
had received at least one dose of HAV vaccine (Havrix, 1440 EIU) were reviewed
for factors associated with the development of a protective anti-HAV response.
Serological data with regard to anti-HAV status after vaccination were available 
in 238 patients with 133 individuals (49.6%) developing immunity after
vaccination. In a logistic regression model, the only factors associated with a
protective antibody response were an HIV plasma RNA level <1000 copies/mL at the 
time of vaccination (P = 0.011) and male gender (P = 0.016). Neither nadir CD4+ T
cell count nor CD4+ T-cell count at time of vaccination were predictive of the
development of anti-HAV. Suppression of HIV replication at time of vaccination is
associated with a protective antibody response to HAV vaccination in HIV-infected
adults. The low rate of response warrants further research in alternative
strategies for HAV vaccination among HIV-infected persons.

PMID: 17305885 [PubMed - indexed for MEDLINE]

153: Clin Infect Dis. 2007 Mar 15;44(6):838-40. Epub 2007 Feb 13.

Use of molecular epidemiology to confirm a multistate outbreak of hepatitis A
caused by consumption of oysters.

Bialek SR, George PA, Xia GL, Glatzer MB, Motes ML, Veazey JE, Hammond RM, Jones 
T, Shieh YC, Wamnes J, Vaughan G, Khudyakov Y, Fiore AE.

Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta,
GA 30333, USA. sbialek@cdc.gov

The 39 oyster consumption-related cases of hepatitis A reported in 2005 represent
the first large outbreak of hepatitis A associated with shellfish consumption in 
the United States in >15 years. This is the first outbreak investigation in which
an identical hepatitis A virus sequence was obtained from both the implicated
food product and case patients.

PMID: 17304457 [PubMed - indexed for MEDLINE]

154: Travel Med Infect Dis. 2007 Mar;5(2):79-84. Epub 2006 Jun 19.

A review of the long-term protection after hepatitis A and B vaccination.

Van Damme P, Van Herck K.

Centre for the Evaluation of Vaccination, WHO Collaborating Centre for Prevention
and Control of Viral Hepatitis, Department of Epidemiology and Social Medicine,
University of Antwerp, Belgium. Pierre.vandamme@ua.ac.be

Vaccine-preventable viral hepatitis continues to be a cause of considerable
morbidity and mortality: on worldwide basis, approximately 1.4 million cases of
hepatitis A are reported every year. The true incidence, however, has been
estimated to be 3-10 times higher. Regarding hepatitis B, more than a third of
the world's population has been infected. The World Health Organization has
estimated (2000) that there are 367 million chronic carriers of hepatitis B
worldwide, and approximately 1 million deaths per year as a consequence of
chronic complications and acute fulminant disease. Hepatitis B vaccines have been
licensed since 1982, and hepatitis A vaccines since 1992. In 1996, a combined
hepatitis A and B vaccine became available. An update on the long-term protection
conferred by hepatitis A and hepatitis B vaccines as well as the combined
hepatitis A and B vaccine is offered in this paper. Long-term efficacy and
booster policy for hepatitis B vaccines have often been a topic of discussion.
Based on current data and field experience there is, in general, no necessity for
booster doses for fully vaccinated immunocompetent individuals. Long-term
protection has been demonstrated by the rapid (5-7 days) development of
anamnestic antibody responses among vaccinees who no longer have detectable
anti-HBs. Anamnestic responses correlate with lymphoproliferative T-cell
responses following challenge with hepatitis B vaccine. Furthermore, employing
Spot-ELISA techniques, circulating B-cells were shown to be able to produce
anti-HBs in vaccinees who lost their detectable antibodies. The accumulated data 
from a large number of studies indicate that despite antibody decline or loss,
immune memory exhibits long-term persistence. There is somewhat less information 
available for hepatitis A vaccines, yet an increasing number of studies indicate 
that the findings for hepatitis B vaccines are also applicable to hepatitis A
vaccines. The necessity to provide a booster dose was based on early projections 
of observed antibody levels. However, recent follow-up studies with up to 12 year
observation, as well as studies employing mathematical models predict that
following primary vaccination, antibodies will persist for at least 25 years. In 
addition, experimental studies confirm that vaccination against hepatitis A
induces immunological memory. Therefore hepatitis A booster vaccination is
presently considered as unnecessary in fully vaccinated individuals. The above
findings are of importance in the context of administering combined hepatitis A
and B vaccine for which similar long-term data have been observed. All available 
data on monovalent and combined hepatitis A and hepatitis B vaccines indicates
that there is no support for a hepatitis A or hepatitis B booster when a complete
primary vaccination course is offered to immunocompetent individuals.

Publication Types: 
    Review

PMID: 17298912 [PubMed - indexed for MEDLINE]

155: J Autoimmun. 2007 Feb;28(1):7-18. Epub 2007 Feb 12.

Autoantibody response to microsomal epoxide hydrolase in hepatitis C and A.

Akatsuka T, Kobayashi N, Ishikawa T, Saito T, Shindo M, Yamauchi M, Kurokohchi K,
Miyazawa H, Duan H, Matsunaga T, Komoda T, Morisseau C, Hammock BD.

Department of Microbiology, Saitama Medical University, Moroyama-cho, Iruma-gun, 
Saitama 350-0495, Japan. akatsuka@saitama-med.ac.jp

Autoimmune responses were observed in a large proportion of hepatitis C cases and
are suspected to be part of viral pathogenesis. The AN6520 antigen (AN-Ag) is a
normal cellular protein mainly expressed in liver that was found associated with 
non-A, non-B hepatitis. To elucidate its pathogenic role in hepatitis C, we
developed an IgM capture assay using purified AN-Ag and confirmed that the
antibody response to AN-Ag is associated almost exclusively with hepatitis C
cases (29%). Screening of a human liver expression library revealed that AN-Ag is
mainly the microsomal epoxide hydrolase (mEH), a drug-metabolizing enzyme that
plays an important role in the metabolism of some mutagenic and carcinogenic
epoxides. Using the purified recombinant human mEH as an antigen, we now found
that antibodies against this protein are associated with nearly 82% of hepatitis 
C virus infections and surprisingly with 46% of patients with hepatitis A. The
appearance of AN-Ag/mEH in the incubation period of hepatitis C as previously
reported and the antibody responses shown here indicate that this enzyme may be a
marker for or even a cause of some of the pathology associated with hepatitis C
and A.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 17296285 [PubMed - indexed for MEDLINE]

156: Mem Inst Oswaldo Cruz. 2007 Feb;102(1):121-3.

Prevalence of hepatitis A virus infection in Afro-Brazilian isolated communities 
in Central Brazil.

Kozlowski AG, Motta-Castro AR, Nascimento LB, Silva AM, Teles SA, Villar LM,
Gaspar AM, Martins RM.

Instituto de Patologia e Saúde Pública, Universidade Federal de Goiás, Goiânia,
Brasil.

To investigate hepatitis A virus (HAV) infection rates among isolated
African-descendant communities in Central Brazil, 947 subjects were interviewed
about demographic characteristics in all 12 isolated Afro-descendant communities 
existing in the state of Mato Grosso do Sul, Central Brazil, between March 2002
and November 2003. Blood samples were collected and sera were tested for HAV
antibodies (total and IgM anti-HAV) by enzyme-linked immunosorbent assay. The
overall prevalence of HAV infection was 75.6% (95% CI: 72.7-78.3), ranging from
55.4 to 97.3%, depending on the communities studied. The prevalence of anti-HAV
increased significantly with age, from 13.8% in the age 0-5 age group to 96.6% in
those older than 40 years. The findings point out an intermediate endemicity of
HAV infection in some Afro-Brazilian isolated communities in Central Brazil. In
addition, the high proportion of susceptible young subjects could be target of
future HAV vaccination programs.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17294012 [PubMed - indexed for MEDLINE]

157: Braz J Infect Dis. 2006 Oct;10(5):317-21.

Serological markers of hepatitis A, B and C viruses in rural communities of the
semiarid Brazilian northeast.

Almeida D, Tavares-Neto J, Vitvitski L, Almeida A, Mello C, Santana D, Tatsch F, 
Paraná R.

Faculty of Medicine of Bahia, Post-graduation Program in Health and Medicine,
Salvador, Bahia, Brazil. delvone@terra.com.br

In the village of Cavunge, located in a dry tropical, semiarid rural region of
the state of Bahia, Brazil, a sentinel study on viral hepatitis is underway. We
report on the first part of the study. The objective of this study was to
determine the prevalence of serological markers for hepatitis A, B and C in the
village. Cross sectional study. Blood samples were tested for serological markers
of hepatitis A (HAV), B (HBV) and C (HCV) through ELISA-III assay. In HBsAg and
anti-HCV carriers, HCV-RNA and HBV-DNA were checked by PCR. The prevalence of
anti-HAV IgG was 83.3% (1,210/1,452), being higher among residents from the
village (87.4%) than in residents from the rural area (79.5%); it also higher
among individuals older than 10 years of age. The prevalence of HBsAg was 2.6%
(38/1,476), 9.3% anti-HBc (137/1,476) and 10.5% (155/1,476) anti-HBs of. In more 
than half (58.1%; 90/155) of anti-HBs carriers, this was the only serological
marker found. In 3.7% of the population, (55/1,476), anti-HBc was the only
serological marker found. All HBV carriers were infected by genotype A. Only 0.4%
(6/1,536) presented anti-HCV antibodies and only one of them was viremic, being
infected with genotype 1. The prevalence of patients with antibodies against
hepatitis A virus in the village of Cavunge was high, but the prevalence of B
virus was moderate, with only genotype A among HBV carriers. The prevalence of C 
virus was very low, contrasting with the situation in large Brazilian urban
centers.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17293918 [PubMed - indexed for MEDLINE]

158: Can J Public Health. 2007 Jan-Feb;98(1):37-40.

Participant-collected, mail-delivered oral fluid specimens can replace
traditional serosurveys: a demonstration-of-feasibility survey of hepatitis A
virus-specific antibodies in adults.

Ochnio JJ, Scheifele DW, Marion SA, Bigham M, Patrick DM, Ho M, Mozel M.

University of British Columbia, Department of Pediatrics, Vaccine Evaluation
Centre, Vancouver. jochnio@interchange.ubc.ca

BACKGROUND: Although population-based serosurveys offer an optimal measure of
cumulative infection rates, they are seldom performed due to high cost and
complex logistics. Use of participant self-collected oral fluid as a diagnostic
specimen and mail for specimen delivery has the potential of generating reliable,
population-representative data at limited cost. METHODS: A survey of oral fluid
HAV-specific immunoglobulin G (an indicator of past HAV infection) was undertaken
in a provincially representative sample of 20-39 year olds as a pilot study. A
provincial administrative database served as the sampling frame. Potential
participants were invited by mail to collect oral fluid and complete a
questionnaire at home and return both by mail. Additional telephone prompting was
directed at slow responders. Oral fluid was tested using a validated ELISA.
RESULTS: From among 2,448 potential participants, contact by mail or telephone
was made with 1,009 eligible subjects; 59% (585) participated. Materials
withstood mailing and the quality of self-collected specimens was excellent. A
positive test result was found in 22.1% overall and in 15.7% of self-reported
non-vaccinated subjects. Among Canadian-born, non-vaccinated individuals, the
positive test rate increased progressively from 1.2% (95% CI: 0-6.3) in 20-24
year olds to 16.4% (95% CI: 9.5-23.3) in 35-39 year olds. Antibody prevalence was
higher among Canadian-born non-immunized 20-29 year olds who reported travel to
developing countries (33.3%, 95% CI: 11.6-55.1) than in non-travellers (2.5%, 95%
CI: 0.7-6.2). CONCLUSIONS: Mail-based population surveys of infection markers in 
oral fluid are feasible provided an appropriate sampling frame is used. This
survey revealed a high anti-HAV antibody prevalence in young Canadian adults,
increasing with age and travel to developing countries.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17278676 [PubMed - indexed for MEDLINE]

159: Drug Alcohol Depend. 2007 Nov;91 Suppl 1:S64-72. Epub 2007 Feb 2.

Convenience is the key to hepatitis A and B vaccination uptake among young adult 
injection drug users.

Campbell JV, Garfein RS, Thiede H, Hagan H, Ouellet LJ, Golub ET, Hudson SM,
Ompad DC, Weinbaum C; DUIT Study Team.

HIV/AIDS Epidemiology Program, Public Health-Seattle & King County, 400 Yesler
Way 3rd Floor, c/o Hanne Thiede, Seattle, WA 98104, USA. jenverncamp@hotmail.com

BACKGROUND: Despite CDC recommendations to vaccinate injection drug users (IDUs) 
against hepatitis A virus (HAV) and hepatitis B virus (HBV) infections, coverage 
remains low. Vaccination programs convenient to IDUs have not been widely
implemented or evaluated. We assessed whether convenience and monetary incentives
influenced uptake of free vaccine by 18-30-year-old IDUs in five U.S. cities.
METHODS: IDUs recruited from community settings completed risk behavior
self-interviews and testing for antibodies to HAV (anti-HAV) and hepatitis B core
antigen (anti-HBc). Vaccine was offered presumptively at pre-test (except in
Chicago); on-site availability and incentives for vaccination differed by site,
creating a quasi-experimental design. RESULTS: Of 3181 participants, anti-HAV and
anti-HBc seroprevalence was 19% and 23%, respectively. Although 83% of
participants were willing to be vaccinated, only 36% received > or =1 dose, which
varied by site: Baltimore (83%), Seattle (33%), Los Angeles (18%), New York
(17%), and Chicago (2%). Participation was highest when vaccine was available
immediately on-site and lowest when offered only after receiving results.
Monetary incentives may have increased participation when on-site vaccination was
not available. CONCLUSION: IDUs were willing to be vaccinated but immediate,
on-site availability was critical for uptake. Convenience should be a key
consideration in designing strategies to increase vaccine coverage among IDUs.

Publication Types: 
    Randomized Controlled Trial
    Research Support, U.S. Gov't, P.H.S.

PMID: 17276018 [PubMed - indexed for MEDLINE]

160: J Food Prot. 2007 Jan;70(1):145-50.

Molecular confirmation of oysters as the vector for hepatitis A in a 2005
multistate outbreak.

Shieh YC, Khudyakov YE, Xia G, Ganova-Raeva LM, Khambaty FM, Woods JW, Veazey JE,
Motes ML, Glatzer MB, Bialek SR, Fiore AE.

U.S. Food and Drug Administration Gulf Coast Seafood Laboratory, Dauphin Island, 
Alabama 36528, USA. carol.shieh@fda.hhs.gov

Numerous hepatitis A outbreaks were linked to the consumption of raw molluscan
shellfish in the United States between 1960 and 1989. However, there had been no 
major molluscan shellfish-associated hepatitis A outbreaks reported in the United
States for more than a decade (1989 to 2004). Beginning in late August 2005, at
least 10 clusters of hepatitis A illnesses, totaling 39 persons, occurred in four
states among restaurant patrons who ate oysters. Epidemiologic data indicated
that oysters were the source of the outbreak. Traceback information showed that
the implicated oysters were harvested from specific Gulf Coast areas. A voluntary
recall of oysters was initiated in September. Hepatitis A virus (HAV) was
detected in multiple 25-g portions in one of two recalled samples, indicating
that as many as 1 of every 15 oysters from this source was contaminated.
Comparing 315 nucleotides within the HAV VPl-2B region, 100% homology was found
among four amplicons recovered from a total of six independent experiments of the
implicated oysters, and an identical HAV sequence was detected in sera from all
28 patient serum specimens tested. Ten percent heterogeneity over 315 nucleotides
(31 variants) was observed between the outbreak strain (subgenotype 1A) and an
HM-175 strain (subgenotype 1B) used in the laboratory where the oysters were
processed. To our knowledge, this investigation is the first in the United States
to identify an HAV-identical strain in persons with hepatitis A as well as in the
food that was implicated as the source of their infections.

PMID: 17265873 [PubMed - indexed for MEDLINE]

161: Mil Med. 2006 Dec;171(12):1196-7.

Disease-modifying effects of postexposure hepatitis A active immunization.

Mimouni D, Bar-Zeev Y, Davidovitch N, Zarka S.

Department of Dermatology, Rabin Medical Center, Beilinson Campus, Petah Tikva,
Israel 49100.

BACKGROUND: Several studies have demonstrated the efficacy of hepatitis A virus
(HAV) active vaccine in the prevention of secondary HAV infection when
administered shortly after exposure. METHODS: We describe six new recruits with
unknown HAV infection, of whom three received late postexposure prophylaxis with 
the active HAV vaccine and three were not vaccinated. RESULTS: Results indicated 
that the vaccinated patients had a longer period from exposure to onset of
symptoms (p < 0.05), shorter hospitalization, and lower liver enzyme levels.
CONCLUSIONS: It appears that late administration of the active HAV vaccine has a 
disease-modifying effect. These findings, combined with earlier reports, may have
important implications for immunization policies.

PMID: 17256681 [PubMed - indexed for MEDLINE]

162: Ann Trop Med Parasitol. 2007 Jan;101(1):61-8.

Declining trend in the seroprevalence of infection with hepatitis A virus in
Thailand.

Chatproedprai S, Chongsrisawat V, Chatchatee P, Theamboonlers A, Yoocharoen P,
Warinsathien P, Tharmaphornpilas P, Warintrawat S, Sinlaparatsamee S, Chaiear K, 
Khwanjaipanich S, Paupunwatana S, Poovorawan Y.

Center of Excellence in Viral Hepatitis Research, Department of Pediatrics,
Faculty of Medicine, Chulalongkorn University, Rama IV Road, Patumwan, Bangkok
10330, Thailand.

Since the mid 1970s, infection with hepatitis A virus (HAV) in Thailand has
shifted from hyper-endemic to mesoendemic. In 2004, to explore this trend in
prevalence further, 3997 subjects from four geographically distinct provinces of 
Thailand were tested, in a commercial ELISA, for antibodies to HAV. The results
indicate that the seroprevalence of HAV continues to fall, almost certainly
because the profound socio-economic development that has occurred over the last
few decades in Thailand has brought with it significant improvements in
sanitation and personal hygiene. As exposure to HAV declines, however, the risks 
of symptomatic and potentially severe infection in adulthood (rather than
asymptomatic infection during childhood) and of epidemics of such infection,
which would lead to profound economic loss, increases. Improvements in hygiene
and sanitation to reduce exposure to the virus and measures to reduce the
incidence of symptomatic disease in those infected, such as vaccination (which
may only be cost-effective when targeted at high-risk groups), need to be
carefully considered.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17244410 [PubMed - indexed for MEDLINE]

163: J Travel Med. 2007 Jan-Feb;14(1):31-6.

Pretravel advice and hepatitis A immunization among Australian travelers.

Zwar N, Streeton CL; Travel Health Advisory Group.

School of Public Health and Community Medicine, University of New South Wales,
Sydney, Australia. n.zwar@unsw.edu.au

BACKGROUND: More Australians are traveling to overseas destinations where
preventable infectious diseases, such as hepatitis A, are endemic. Yet, there is 
only limited data concerning the extent to which Australians seek travel advice
and vaccination before their departures. METHOD: Annual telephone surveys were
conducted among adult Australians travelers. Information was collected on the
travel advice and vaccinations received before departure. Perceptions about, and 
their potential exposure to, travel-related infections while overseas were also
assessed. This paper presents data from the 2003 survey related to travel advice 
and hepatitis A, while hepatitis B is discussed in the companion article.
RESULTS: Only a third of interviewees had sought health advice before travel.
Infrequent travelers, those departing for endemic countries or for longer
journeys, were more likely to seek medical advice. Overall, 32% of interviewees
had been vaccinated against hepatitis A, with travelers to high/medium-hepatitis 
A endemicity destinations being more likely to be vaccinated than those visiting 
low-endemicity countries (44% vs 20%). Among the 263 visitors to endemic
countries, those who stayed with friends and relatives were least likely to be
vaccinated against hepatitis A compared to other styles of accommodation.
CONCLUSIONS: Despite government recommendations and industry group campaigns
about the need for pretravel advice, the majority of Australians travel overseas 
without adequate health advice and protection against hepatitis A and other
travel-related infectious diseases.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17241251 [PubMed - indexed for MEDLINE]

164: J Travel Med. 2007 Jan-Feb;14(1):9-15.

Rapid and sustained immune response against hepatitis A and B achieved with
combined vaccine using an accelerated administration schedule.

Connor BA, Blatter MM, Beran J, Zou B, Trofa AF.

Division of Gastroenterology and Hepatology, The Weill Medical College of Cornell
University, New York, NY, USA.

BACKGROUND: Combined hepatitis A and B vaccine administered on an accelerated
schedule provides a rapid immune response against both hepatitis A and B viruses,
which might be especially relevant for individuals who need protection quickly.
METHODS: A prospective, open-label, randomized study to compare the
immunogenicity and reactogenicity of the combined hepatitis A and B vaccine
Twinrix (GlaxoSmithKline Biologicals, Rixensart, Belgium) (>or=720 EL.U/mL
inactivated hepatitis A antigen and 20 microg/mL recombinant hepatitis B surface 
antigen [HBsAg]) administered at 0, 7, 21 to 30 days, and 12 months compared with
concurrent administration of Havrix [GlaxoSmithKline Biologicals, Rixensart,
Belgium (>or=1440 EL.U/mL inactivated hepatitis A antigen)] at 0 and 12 months,
and Engerix-B [GlaxoSmithKline Biologicals, Rixensart, Belgium (20 microg/mL
recombinant HBsAg)] at 0, 1, 2, and 12 months in seronegative healthy adults.
RESULTS: At month 13, the anti-hepatitis B seroprotection rates (>10 mIU/mL) for 
the combined vaccine compared to the monovalent hepatitis B vaccine were 96.4%
(95% CI: 92.7-98.5) and 93.4% (95% CI: 89.0-96.4), respectively. The
anti-hepatitis A seroconversion rates were 100% in both groups (95% CI:
98.1-100). At day 37, the anti-hepatitis A seroconversion rates were similar in
both groups (98.5% for combined vaccine, 98.6% for the monovalent vaccine group),
but the combined vaccine resulted in a statistically significantly ( p < 0.001)
better anti-hepatitis B seroprotection compared to monovalent hepatitis B
vaccine, 63.2% versus 43.5%, respectively. The reactogenicity profile was similar
in both study groups. CONCLUSIONS: The combined hepatitis A and B vaccine
administered on an accelerated schedule was at least as immunogenic and as well
tolerated as the corresponding monovalent vaccines.

Publication Types: 
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 17241248 [PubMed - indexed for MEDLINE]

165: Vaccine. 2007 Feb 26;25(10):1719-26. Epub 2006 Nov 27.

A dynamic model for assessing universal Hepatitis A vaccination in Canada.

Bauch CT, Rao AS, Pham BZ, Krahn M, Gilca V, Duval B, Chen MH, Tricco AC.

Department of Mathematics and Statistics, University of Guelph, Canada.
cbauch@uoguelph.ca

Vaccination against Hepatitis A virus (HAV) in Canada is currently targeted
toward high-risk groups. However, universal vaccination has been adopted in
several other countries with a similar disease burden. Here we develop an
age-structured compartmental model of HAV transmission and vaccination in Canada 
to assess potential universal vaccination strategies. The model predicts that
universal vaccination at age 1 (respectively 4, 9, 15), with phasing out of
targeted vaccination, would reduce reported incidence by 60% (respectively 52,
36, 31%) and mortality attributable to HAV by 56% (respectively 45, 26, 25%),
relative to continued targeted vaccination, over 80 years.

PMID: 17229493 [PubMed - indexed for MEDLINE]

166: Hum Vaccin. 2006 Nov-Dec;2(6):233-6. Epub 2006 Nov 2.

large-scale serologic testing program to assess the immunogenicity of inactivated
hepatitis a vaccine (VAQTA) in prefilled syringes following product recall in
Germany.

Jäger G, Kuter B, Campe H, Lakkis H, Nitschko H, Watson M, Harzer E, Schödel F.

Max von Pettenkofer-Institut für Hygiene und Medizinische Mikrobiologie, München,
Germany. jaeger@mvp.uni-muenchen.de

A voluntary recall of VAQTA in prefilled syringes was implemented in Europe in
late 2001 after the manufacturer noted a slight decrease in the antigen content
of a small percentage of the syringes manufactured over a particular time frame. 
In Germany, a large-scale serologic testing program was implemented. The assay
results were conveyed to the subject's physician, and free vaccine was provided
for anyone requesting revaccination. An analysis was performed on a subset of
58,546 vaccine recipients with hepatitis A antibody results. Of the 28,681
persons who received either two 25 units (25 U) or two 50 units (50 U) doses of
VAQTA, the seropositivity rate (SPR) was 99.5% after receipt of 2 doses, similar 
to the results in prelicensure clinical trials. The SPR was similar among
recipients of lots that had been manufactured over the time frame associated with
the recalled lots versus those receiving lots not associated with the recalled
lots (25U: 99.7% versus 99,7%; 50U: 98.6% versus 99.6%, respectively). There were
less recipients of 25U doses of the affected lots, who had high hepatitis A
antibody titers (> or =100 mIU/mL), compared to recipients of unaffected lots.

PMID: 17204866 [PubMed - indexed for MEDLINE]

167: Pediatrics. 2007 Jan;119(1):e22-9.

The economics of routine childhood hepatitis A immunization in the United States:
the impact of herd immunity.

Armstrong GL, Billah K, Rein DB, Hicks KA, Wirth KE, Bell BP.

Division of Viral Hepatitis, National Center for Infectious Diseases, Centers for
Disease Control and Prevention, 1600 Clifton Rd NE, Atlanta, GA 30333, USA.
garmstrong@cdc.gov

OBJECTIVES: Because of the herd-immunity phenomenon, the benefits of immunization
against hepatitis A extend beyond those received by those who are vaccinated.
This analysis estimates the impact of herd immunity on the cost-effectiveness of 
routine hepatitis A immunization among US children. PATIENTS AND METHODS: In an
economic model, the costs and benefits of hepatitis A immunization were estimated
for immunizing all US children at age 1 year over a 10-year period starting in
2005. The future burden of disease from hepatitis A was also estimated with this 
model, and the fraction that would be prevented by herd immunity was modeled by
using a previously published analysis of the relationship between hepatitis A
vaccination coverage and declines in hepatitis A incidence. RESULTS: Without
accounting for herd-immunity effects, the costs of routine immunization would
average 32,000 dollars per quality-adjusted life-year gained for the first 10
cohorts immunized starting with the 2005 birth cohort. Herd-immunity effects
would be expected to produce substantial additional benefits, lowering the cost
of the immunization program to 1000 dollars per quality-adjusted life-year gained
for the first 10 cohorts. Herd-immunity benefits would be greatest for the first 
few cohorts, more than doubling the benefits of immunization, and would decline
over time. In a univariate sensitivity analysis, estimates were most sensitive to
vaccination costs but remained below 20,000 dollars per quality-adjusted
life-year under all of the assumptions. CONCLUSIONS: Herd-immunity effects more
than double the savings from hepatitis A immunization during the first 10 years
of the program. After accounting for these effects, immunization is close to
cost-neutral on a cost-per-quality-adjusted-life-year basis.

PMID: 17200247 [PubMed - indexed for MEDLINE]

168: Pediatrics. 2007 Jan;119(1):e12-21.

Cost-effectiveness of routine childhood vaccination for hepatitis A in the United
States.

Rein DB, Hicks KA, Wirth KE, Billah K, Finelli L, Fiore AE, Hoerger TJ, Bell BP, 
Armstrong GL.

RTI International, 2951 Flowers Rd, Suite 119, Atlanta, GA 30306, USA.
drein@rti.org

OBJECTIVES: Economic analysis is an important component in formulating national
policy. We evaluated the economic impact of hepatitis A vaccination of all US
children ages 12 to 23 months as compared with no vaccination and with current
implementation of the preexisting (issued in 1999), regional policy. METHODS: We 
developed a Markov model of hepatitis A that followed a single cohort from birth 
in 2005 through death or age 95 years. From the societal perspective, the model
compared the outcomes that resulted from routine vaccination at age 1 year to 2
scenarios: no hepatitis A vaccination and hepatitis A vaccination at levels
observed in 2003 under the preexisting policy. We evaluated the economic impact
of vaccination nationwide, in areas where vaccination was already recommended,
and in areas where no previous recommendation existed. RESULTS: Without childhood
vaccination, the approximately 4 million children in the 2005 birth cohort would 
be expected over their lifetimes to have 199,000 hepatitis A virus infections,
including 74,000 cases of acute hepatitis A and 82 deaths, resulting in 134
million dollars in hepatitis A-related medical costs and productivity losses.
Compared with no vaccination, routine vaccination at age 1 year would prevent
172,000 infections, at a cost of 28,000 dollars per quality-adjusted life year
saved. Compared with maintaining the levels of hepatitis A vaccination under the 
preexisting regional policy, routine vaccination at age 1 year would prevent an
additional 112,000 infections, at a cost of 45,000 dollars per quality-adjusted
life year saved. CONCLUSIONS: The cost-effectiveness of nationwide hepatitis A
vaccination compared with no vaccination, and the incremental cost-effectiveness 
of this recommendation compared with preexisting recommendations, is similar to
that of other accepted public health interventions. In October 2005, the Advisory
Committee on Immunization Practices recommended extending hepatitis A
immunization to all US children ages 12 to 23 months.

PMID: 17200237 [PubMed - indexed for MEDLINE]

169: Pediatr Infect Dis J. 2007 Jan;26(1):36-40.

Elimination of hepatitis a infection outbreaks in day care and school settings in
southern Israel after introduction of the national universal toddler hepatitis a 
immunization program.

Belmaker I, Dukhan L, Yosef Y, Leventhal A, Dagan R.

Ministry of Health, Southern Regional Office, Beer Sheva, Israel.
ilna.belmaker@lbr.health.gov.il

BACKGROUND: In 1999, Israel became the first country to begin universal toddler
immunization against hepatitis A infection with a 2-dose schedule at 18 and 24
months. The effect of the Israeli program on outbreaks of Hepatitis A in day care
and school settings was studied. METHODS: The records of all hepatitis A illness 
outbreaks in day care and school settings reported to the Ministry of Health in
Southern Israel during 1993 through 2005 were reviewed. The number of exposed
contacts for whom postexposure prophylaxis was administered was retrieved from
records of epidemiologic investigations. Rates of immunization coverage were
extracted from records of Maternal and Child Health Clinics. RESULTS: Three
hundred nineteen cases of hepatitis A illness during the years 1993 through 2005 
were associated with 113 outbreaks in day care and school settings of which 92%
occurred before the institution of universal toddler immunization. Since 2000, no
hepatitis A infection outbreaks have been reported in any day care and school
settings in the region. An average of 732 children received immunoglobulin
prophylaxis yearly because of exposure to an outbreak in an educational setting
during the preimmunization period, 106 in 2000 and zero in the 5 years since
2001. The data showed marked herd immunity since school-aged children born before
1999 were not immunized, but elimination of outbreaks occurred equally in that
age group. Immunization coverage was 86.4% for one dose of hepatitis A vaccine by
age 3 years and 77.3% for 2 doses among the birth cohort of 2000. CONCLUSIONS:
Universal hepatitis A immunization of toddlers was associated with disappearance 
of outbreaks in educational settings. This included cohorts of nonimmunized
children representing marked herd immunity.

PMID: 17195703 [PubMed - indexed for MEDLINE]

170: Clin Microbiol Infect. 2007 Jan;13(1):25-32.

A 1-year study of the epidemiology of hepatitis A virus in Tunisia.

Gharbi-Khelifi H, Sdiri K, Ferre V, Harrath R, Berthome M, Billaudel S, Aouni M.

Laboratoire des Maladies Transmissibles et Substances Biologiquement Actives,
Faculté de Pharmacie de Monastir, Monastir, Tunisia.

This 1-year (September 2000 to August 2001) prospective study investigated the
presence of hepatitis A virus (HAV) in the population of Monastir, Tunisia (86
serum samples), in the influents and effluents of two wastewater treatment
plants, and in shellfish harvested in the coastal areas of Monastir, Bizerte and 
Sfax (January 2001 to May 2001). The virus was detected by RT-PCR using primers
targeted at the VP3-VP1 region. An epidemic of HAV infection was observed during 
the winter months, with a peak in January. The presence of the virus was
relatively constant in the influents and effluents of the wastewater treatment
plants, and the virus was found in shellfish from the Monastir area during the
months of January and February. The genotype IA strain was recovered most
frequently from human serum and wastewater samples. The observation that the peak
of the epidemic was during the winter months suggests that transmission of HAV is
related to climatic factors and, presumably, to shellfish consumption.

PMID: 17184284 [PubMed - indexed for MEDLINE]

171: Turk J Pediatr. 2006 Jul-Sep;48(3):189-96.

The prevalence of atopy in children with antibodies against hepatitis A virus and
hepatitis B virus.

Kocabaş E, Yapicioğlu H, Yildizdaş D, Güneşer Kendirli S, Burgut R.

Department of Pediatrics, Cukurova University Faculty of Medicine, Adana, Turkey.

To investigate the relationship between atopy and hepatitis A virus (HAV) and
hepatitis B virus (HBV) infections, we studied 42 children who had had HAV
infection (Group I), 28 children who had had HBV infection (Group II), and 31
children who were seronegative for both HAV and HBV infection (Control group).
Serological tests for HAV and HBV infections (anti-HAV IgG, HBsAg, anti-HBc IgG) 
and allergic skin tests and specific IgE investigations for the detection of
atopy were carried out. In this study, there was no significant divergence in the
socio-demographic characteristics among the three groups. The rates of specific
IgE positivity in children in the HAV seropositive group (11.9%) and in children 
in the HBV seropositive group (17.8%) were lower than in the control group
(35.4%) (p = 0.03 and p = 0.22, respectively). Also, the number of children with 
respiratory allergic diseases (allergic rhinitis and/or asthma) both in the HAV
seropositive group and in the HBV seropositive group were significantly lower
than in the control group (p < 0.05). When atopy in all of the groups was
evaluated, the prevalence of atopy was found to be more widespread in HAV
seronegative children (Adjusted OR, 9.2; 95% CI, 1.7-48.2) and HBV seronegative
children (Adjusted OR, 5.9; 95% CI, 1.1-31.8) than in HAV and HBV seropositive
children, after adjustment for age, number of older siblings and education of the
father. In conclusion, in this study, the prevalence of atopy in children who had
had HAV or HBV infection was found to be low, and this situation was considered
to be related to the relationship of HAV and HBV infections to poor hygiene and
to the fact that these infections occur at early ages in Turkey.

PMID: 17172060 [PubMed - indexed for MEDLINE]

172: Eur J Epidemiol. 2006;21(12):893-9. Epub 2006 Dec 8.

Long-term protective effect of post-exposure Havrix administration during viral
hepatitis Type A outbreaks.

Kohl I, Nemecek V, Summerová M, Chlíbek R, Nad'ová K, Mináriková O.

GlaxoSmithKline, Na Pankraci 17/1685, 140 21, Prague 4, Czech Republic.
igor.i.kohl@gsk.com

Administration of human normal immunoglobulin (HNIG) post-exposure has been
routinely used in Slovakia for outbreak control of hepatitis A, but requires deep
intramuscular injection, provides only short-lived protection and is a human
blood product. The protective effect of post-exposure administration of an
inactivated hepatitis A vaccine was evaluated during 10 outbreaks in Slovakia.
Direct contacts of confirmed hepatitis A cases received either: a single dose of 
hepatitis A vaccine (n = 2171) or immunoglobulin (HNIG, n = 3837). In the HNIG
group the number of hepatitis A confirmed cases dropped within the first 7 weeks,
however the decrease was not as rapid or as marked as that observed in the
vaccinated group where the number of hepatitis A cases dropped within the first 4
weeks after vaccination. Among contacts, 67 cases of hepatitis A were detected
during the maximum incubation period of 45 days: 16 cases (0.7%) in the vaccine
group and 51 cases (1.3%) in the HNIG group (p < 0.05). After two and three years
respectively, 50 and 39 volunteers who had previously received one dose of
hepatitis A vaccine received a booster dose and anti-HAV antibodies were
measured. Differences in anti-HAV antibody GMCs before and after the booster were
statistically significant. The longer time interval (3 years instead of 2)
between primary vaccination and booster administration did not seem to impact the
magnitude of the booster response. The results of this study show that active
post-exposure immunisation with only one dose of inactivated vaccine confers high
and long-term protection and effectively controls viral hepatitis A outbreaks.

Publication Types: 
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 17160428 [PubMed - indexed for MEDLINE]

173: Vaccine. 2007 Feb 19;25(9):1662-8. Epub 2006 Nov 13.

The first experimental study on a candidate combined vaccine against hepatitis A 
and hepatitis E.

Dong C, Dai X, Meng JH.

Department of Microbiology and Immunology, School of Medicine, Southeast
University, 87 Dingjiaqiao Road, Nanjing 210009, China.

To test the possibility of developing a combined vaccine against hepatitis A and 
E, groups of mice were immunized with different formulations containing different
dosages of a commercially inactivated hepatitis A vaccine and a candidate
recombinant hepatitis E vaccine. Monovalent vaccine components were used as
controls. The experimental results showed that the combined vaccine could induce 
neutralizing antibodies against both hepatitis A virus (HAV) and hepatitis E
virus (HEV) effectively in mice. Moreover, the inactivated hepatitis A vaccine
could increase the immunogenicity of the recombinant HEV protein, and the
recombinant HEV protein had no adverse effects on the immunogenicity of the
inactivated HAV vaccine. Thus, the present study demonstrates an important first 
step for the further development of a combined hepatitis A and E vaccine.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17156900 [PubMed - indexed for MEDLINE]

174: BMC Health Serv Res. 2006 Dec 8;6:157.

A review of interventions triggered by hepatitis A infected food-handlers in
Canada.

Tricco AC, Pham B, Duval B, De Serres G, Gilca V, Vrbova L, Anonychuk A, Krahn M,
Moher D.

Epidemiology and Biostatistics, GlaxoSmithKline Canada, Mississauga, Ontario,
Canada. atricco@cheo.on.ca

BACKGROUND: In countries with low hepatitis A (HA) endemicity, infected food
handlers are the source of most reported foodborne outbreaks. In Canada,
accessible data repositories of infected food handler incidents are not
available. We undertook a systematic review of such incidents to evaluate the
extent of viral transmission through food contamination and the scope of
post-exposure prophylaxis (PEP) interventions. METHODS: A systematic search of
MEDLINE and EMBASE was conducted to identify published reports of incidents in
Canada. An expanded search of a news repository (i.e., transcripts from
newspapers and newscasts) was also conducted to identify the location and timing 
of an incident, which was used to retrieve the related report by contacting local
public health departments. Data pertaining to case identification, public health 
risk, PEP interventions, and associated costs was independently abstracted by two
reviewers and summarized according to incidents with and without large PEP
interventions. RESULTS: A total of 16 incidents were identified from 1998-2004.
There were approximately 3 incidents requiring public notification per year. Only
12.5% of incidents were described in published reports, indicating that published
data significantly underestimated the number of incidents and PEP interventions. 
Data pertaining to the remaining incidents was unpublished, sparse and highly
dispersed at the local public health level.Six of the 16 incidents required large
PEP interventions to immunize on average 5000 potentially exposed individuals.
Secondary transmission was low. Characteristics of incidents requiring large PEP 
interventions included potentially infectious food handlers working with uncooked
food for a prolonged duration in high-volume grocery stores in high-density urban
areas. CONCLUSION: Infected food handlers with hepatitis A virus (HAV) requiring 
public notification are not infrequent in Canada. Published data severely
underestimated the burden of PEP intervention. Better and consistent reporting at
the local and national level as well as a national data repository should be
considered for the management of future incidents.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 17156461 [PubMed - indexed for MEDLINE]

175: BMC Infect Dis. 2006 Dec 5;6:174.

Cohort effects in dynamic models and their impact on vaccination programmes: an
example from hepatitis A.

Srinivasa Rao AS, Chen MH, Pham BZ, Tricco AC, Gilca V, Duval B, Krahn MD, Bauch 
CT.

Department of Mathematics and Statistics, University of Guelph, Guelph, Canada.
arni@maths.ox.ac.uk <arni@maths.ox.ac.uk>

BACKGROUND: Infection rates for many infectious diseases have declined over the
past century. This has created a cohort effect, whereby older individuals
experienced a higher infection rate in their past than younger individuals do
now. As a result, age-stratified seroprevalence profiles often differ from what
would be expected from constant infection rates. METHODS: Here, we account for
the cohort effect by fitting an age-structured compartmental model with declining
transmission rates to Hepatitis A seroprevalence data for Canadian-born
individuals. We compare the predicted impact of universal vaccination with and
without including the cohort effect in the dynamic model. RESULTS: We find that
Hepatitis A transmissibility has declined by a factor of 2.8 since the early
twentieth century. When the cohort effect is not included in the model, incidence
and mortality both with and without vaccination are significantly over-predicted.
Incidence (respectively mortality) over a 20 year period of universal vaccination
is 34% (respectively 90%) higher than if the cohort effect is included. The
percentage reduction in incidence and mortality due to vaccination are also
over-predicted when the cohort effect is not included. Similar effects are likely
for many other infectious diseases where infection rates have declined
significantly over past decades and where immunity is lifelong. CONCLUSION:
Failure to account for cohort effects has implications for interpreting
seroprevalence data and predicting the impact of vaccination programmes with
dynamic models. Cohort effects should be included in dynamic modelling studies
whenever applicable.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 17147828 [PubMed - indexed for MEDLINE]

176: J Med Virol. 2007 Jan;79(1):18-25.

Comparison of hepatitis A and E virus infections among healthy children in
Mongolia: evidence for infection with a subgenotype IA HAV in children.

Tsatsralt-Od B, Takahashi M, Endo K, Agiimaa D, Buyankhuu O, Okamoto H.

Division of Virology, Department of Infection and Immunity, Jichi Medical
University School of Medicine, Tochigi-Ken, Japan.

To compare the epidemiologic profiles of hepatitis A virus (HAV) and hepatitis E 
virus (HEV) infections in children in Mongolia, the prevalence of HAV and HEV
infections was investigated serologically and molecularly among 717 apparently
healthy individuals of 0-20 years of age (mean +/- standard deviation, 8.6 +/-
4.9 years) using serum samples obtained between October 2005 and January 2006.
Total antibody against HAV (anti-HAV [total]) was detected in 494 (68.9%) of the 
717 subjects, while IgG antibody against HEV (anti-HEV IgG) was detected in only 
five subjects (0.7%) (P < 0.0001). All five subjects who had anti-HEV IgG, were
negative for anti-HEV IgM and HEV RNA. Anti-HAV was detectable in 24 (75.0%) of
the 32 infants aged 7 days to 6 months, but not in any of the 8 infants aged 7 to
<12 months. The prevalence of anti-HAV was 19.5% (17/87) in the age group of 1-3 
years, and it increased to 50.0% (69/138) in the age group of 4-6 years, and
further to 81.4% (105/129) in the age group of 7-9 years. Of note, 97.2% of the
subjects in the age group of 16-20 years had anti-HAV. The presence of HAV RNA
was tested in all 717 subjects, and three children of 1, 4, or 8 years of age
were found to have detectable HAV RNA (subgenotype IA). No subject had a history 
of hepatitis or jaundice. In conclusion, HEV infection was uncommon, but HAV
infection lacking overt clinical features was prevalent among children in
Mongolia.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 17133554 [PubMed - indexed for MEDLINE]

177: J Med Virol. 2007 Jan;79(1):8-17.

Analysis of the full-length genome of a subgenotype IIIB hepatitis A virus
isolate: primers for broadly reactive PCR and genotypic analysis.

Endo K, Inoue J, Takahashi M, Mitsui T, Masuko K, Akahane Y, Okamoto H.

Division of Virology, Department of Infection and Immunity, Jichi Medical
University School of Medicine, Tochigi-Ken, Japan.

Among six known subgenotypes (IA, IB, IIA, IIB, IIIA, and IIIB) of human
hepatitis A virus (HAV), the complete genomic sequence has not been determined
for IIIB. In this study, the full-length genomic sequence of a IIIB HAV isolate
(HA-JNG06-90F) recovered from a Japanese patient who contracted sporadic
hepatitis A in 1990, was determined. The HA-JNG06-90F genome, which comprised
7462 nt excluding the poly(A) tail, was related most closely to NOR-21 of
subgenotype IIIA with an identity of 89.1%, and was only 82.6-83.4% similar to
human HAV isolates of genotypes I and II over the entire genome. Comparison of
full-length genomic sequences of 20 reported isolates and HA-JNG06-90F generated 
optimal results for separation of different levels: the nucleotide identities
were 80.7-86.6% at the genotype level, 89.1-91.9% at the subgenotype level, and
94.6-99.7% at the isolate level. Similar ranges of nucleotide identity were
observed when comparing partial nucleotide sequences of the VP1-2B (481 nt;
primer sequences at both ends excluded) and 3C/3D (590 nt) regions, which were
amplifiable by PCR with primers designed from well-conserved areas of the HAV
genome. All 66 samples with IgM-class HAV antibodies tested positive for HAV RNA 
by both VP1-2B (481 nt)-PCR and 3C/3D (590 nt)-PCR: subgenotype assignment was
concordant in all samples tested (IA [n = 61], IB [n = 1], IIIA [n = 2] and IIIB 
[n = 2]). These results suggest that two broadly reactive PCRs using primers
derived from the VP1-2B and 3C/3D regions, respectively, may be applicable to
universal detection and phylogenetic analysis of various HAV strains.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17133545 [PubMed - indexed for MEDLINE]

178: Hepatology. 2006 Dec;44(6):1589-97.

Comment in:
    Hepatology. 2006 Dec;44(6):1397-9.

Fulminant hepatitis A virus infection in the United States: Incidence, prognosis,
and outcomes.

Taylor RM, Davern T, Munoz S, Han SH, McGuire B, Larson AM, Hynan L, Lee WM,
Fontana RJ; US Acute Liver Failure Study Group.

Department of Internal Medicine, University of Michigan, Ann Arbor, MI
48109-0362, USA.

Acute liver failure (ALF) due to hepatitis A virus (HAV) infection is an uncommon
but potentially lethal illness. The aim of this study was to identify readily
available laboratory and clinical features associated with a poor prognosis among
ALF patients with HAV infection. The presenting features of 29 adults with
anti-HAV IgM positive ALF enrolled in the ALFSG_between 1998 and 2005 were
reviewed. The HAV patients listed for transplantation by UNOS were also reviewed.
Acute HAV accounted for 3.1% of patients enrolled in the ALFSG. At 3 weeks
follow-up, 16 had spontaneously recovered (55%), 9 underwent transplantation
(31%), and 4 had died (14%). A prognostic model incorporating 4 presenting
features (serum ALT <2,600 IU/L, creatinine >2.0 mg/dL, intubation, pressors) had
an AUROC for transplant/death of 0.899 which was significantly better than the
King's College criteria (0.623, P = .018) and MELD scores (0.707, P = .0503).
Between 1988 and 2005, the frequency of patients requiring liver transplantation 
for HAV in the UNOS database significantly decreased from 0.7 % to 0.1% (P <
.001). In addition, the proportion of HAV cases enrolled in the ALFSG
significantly decreased from 5% to 0.8% (P = .007). In conclusion, the frequency 
of HAV patients enrolling in the ALFSG and being listed for liver transplantation
in the United States has declined in parallel. A prognostic index consisting of 4
clinical and laboratory features predicted the likelihood of transplant/death
significantly better than other published models suggesting that disease specific
prognostic models may be of value in non-acetaminophen ALF.

Publication Types: 
    Multicenter Study
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 17133489 [PubMed - indexed for MEDLINE]

179: Pediatr Infect Dis J. 2006 Dec;25(12):1184-6.

Comparison of trip characteristics of children and adults with travel-acquired
hepatitis A infection.

Gosselin C, De Serres G, Rouleau I, Duval B, Shadmani R, Naus M, Ward BJ.

Public Health Research Unit, CHUL Research Centre, Laval University, Québec,
Canada.

We compared the trip characteristics of 84 child and 99 adult cases with
travel-acquired hepatitis A (HA). Most pediatric cases had traveled in Asia for
more than 30 days and had stayed and eaten most of their meals in the homes of
friends and relatives in a country where they had not been born. In contrast, the
adults with travel-acquired HA had visited Latin America or the Caribbean for 14 
days or less and had stayed primarily in hotels. Specific public health
interventions should be undertaken to prevent HA in traveling children.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 17133168 [PubMed - indexed for MEDLINE]

180: Acta Paediatr. 2006 Dec;95(12):1582-5.

Immunogenicity of hepatitis A-inactivated vaccine administered to seronegative
infants, and serological follow-up 12 months after second dose.

De Silvestri A, Zara F, Terulla V, Brerra R, Zucca S, Belloni C.

Division of Neonatal Care, IRCCS S. Matteo, Pavia, Italy.
a.desilvestri@smatteo.pv.it

AIM: To evaluate a) the safety and immunogenicity of anti-HAV-inactivated vaccine
administered during the first year of life to anti-HAV seronegative babies, and
b) the antibody persistence in a low/intermediate endemic area. METHODS: After
having obtained informed written consent from mothers, 92 babies were vaccinated 
at 4 and 10 mo of age. All babies were seronegative at birth and did not present 
HAV-RNA shedding in three serial stool samples taken at 1, 2 and 3 mo of age.
RESULTS: No general side effects (fever > 38 degrees C) were observed. After the 
first dose of vaccine, 70/82 (85.4%) babies developed anti-HAV > 10 mIU/ml and
36/82 (43.9%) > 20 mIU/ml. After the second dose of vaccine, all babies developed
a titre > 20 mIU/ml, and GMT was 877 mIU/ml. After 1 y of follow-up, the
decreasing rate was similar to that reported for adult populations. Furthermore, 
three babies doubled the titre observed 1 mo after the second dose, indicating
the possible spread of HAV even in a low/intermediate endemic area. CONCLUSION:
Anti-HAV vaccine is safe, immunogenic and able to induce immune memory, and can
be integrated into the routine infant immunization schedule during the first year
of life.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17129966 [PubMed - indexed for MEDLINE]

181: Travel Med Infect Dis. 2006 Dec;4(6):303-12. Epub 2005 Nov 28.

Hepatitis A vaccines and the elderly.

Genton B, D'Acremont V, Furrer HJ, Hatz C, Louis Loutan.

Travel Clinic, Medical Outpatient Clinic, University of Lausanne, Rue du Bugnon
44, 1011, CH-1011 Lausanne, Switzerland. Blaise.genton@hospvd.ch

Hepatitis A virus (HAV) exposure in unprotected adults may cause severe and
serious symptoms, with risk of both morbidity and mortality increasing with age. 
As seroprevalence of HAV is low in industrialised countries, and an increasing
number of people, with an increasing median age, travel from areas of low HAV
endemicity to high endemicity, pre-travel vaccination is warranted. Vaccination
of the elderly against HAV, however, may be associated with reduced
seroprotection, since the immune response decreases with age. Studies with
monovalent hepatitis A vaccine or combined hepatitis A and B vaccine show good
efficacy in adults in general. Few studies have assessed the immune response in
older adults. The only prospective study with monovalent hepatitis A vaccine in
the elderly showed a reduced seroprotection of approximately 65% after a single
primary dose in subjects over the age of 50 years, while seroprotection was 98%
in this age group after receiving a booster dose. The only prospective study with
combined hepatitis A and B vaccine in younger subjects or older than 40 years
showed similar seroprotection (99-100%) against HAV compared to a monovalent
vaccine after receiving three doses. As data on seroprotection for HAV in the
elderly are limited, further studies are needed to elucidate how optimal
protection in the elderly can be achieved. In the mean time, based on the
available data, the suggestion is made to screen elderly travellers to areas
endemic for HAV for the presence of naturally acquired immunity, and, if found
susceptible, be immunised well in advance of their trip, to allow time for
post-vaccination antibody testing and/or administration of a second dose of the
vaccine.

Publication Types: 
    Review

PMID: 17098625 [PubMed - indexed for MEDLINE]

182: J Gastroenterol. 2006 Oct;41(10):981-6. Epub 2006 Nov 9.

Molecular epidemiology of hepatitis A virus in metropolitan areas in Japan.

Takahashi H, Yotsuyanagi H, Yasuda K, Koibuchi T, Suzuki M, Kato T, Nakamura T,
Iwamoto A, Nishioka K, Iino S, Koike K, Itoh F.

Department of Internal Medicine, Division of Gastroenterology and Hepatology,
Institute of Medical Science, St Marianna University, Kawasaki, Japan.

BACKGROUND: Transmission routes of hepatitis A virus (HAV) in Japan have changed.
The present study investigated changes of transmission routes in relation to
genetic drift. METHODS: All 60 patients who were admitted between 1993 and 2003
with a diagnosis of hepatitis A were retrospectively analyzed. Nucleotide
sequences of the VP1/2A region of the HAV recovered from their sera were
determined. RESULTS: The suspected transmission routes were household contact, 19
(31%); food or waterborne, 16 (27%); homosexual activity, 11 (18%); international
travel, 4 (7%); and unknown 10. (17%). The 11 patients presumably infected
through homosexual activity were found exclusively in 1998 and 1999. The
proportion of patients exposed through homosexual behavior and household contact 
was higher in those 2 years than in other years. Nucleotide sequences could be
determined for 58 patients. Fifty-seven of the 58 sequences belonged to genotype 
IA HAV, with less than 10% nucleotide diversity. Of the 27 sequences isolated
during 1998 and 1999, 25 had an identical nucleotide sequence regardless of the
suspected transmission route. In contrast, sequences obtained in the other years 
differed from one another. A phylogenetic tree constructed from sequences
recovered from patients without a history of travel abroad showed several
clusters. CONCLUSIONS: Our results suggest that (1) HAV acquired through
homosexual activity may be transmitted to nonhomosexual individuals; (2)
hepatitis A in metropolitan areas in Japan is caused mainly by sporadic infection
with genotype IA HAV; and (3) several subtypes of genotype IA HAV are endemic in 
Japan.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17096067 [PubMed - indexed for MEDLINE]

183: Trop Gastroenterol. 2006 Apr-Jun;27(2):89-90.

Pancytopenia in a child associated with hepatitis A infection.

Walia A, Thapa BR, Das R.

Division of Pediatric Gastroenterology, Hepatology and Nutrition, PGIMER, Sector 
12 Chandigarh, 160012.

Pancytopenia is a very rare condition associated with hepatitis A infection. We
managed a 12 year old boy who had hepatitis A infection with anemia. His hemogram
and bone marrow examination were suggestive of pancytopenia. Pancytopenia
recovered without any specific therapy. There are case reports of severe aplastic
anemia with hepatitis A infection that required immunosuppressive therapy. The
present case did not require any aggressive therapy and recovered. In a young
child with hepatitis A infection and anemia, bone marrow depression should be
suspected. The pancytopenia may be transient as exemplified by the present case.

Publication Types: 
    Case Reports

PMID: 17089620 [PubMed - indexed for MEDLINE]

184: Infect Control Hosp Epidemiol. 2006 Nov;27(11):1178-83. Epub 2006 Oct 17.

Seroprevalence survey of varicella, measles, rubella, and hepatitis A and B
viruses in a multinational healthcare workforce in Saudi Arabia.

Almuneef MA, Memish ZA, Balkhy HH, Otaibi B, Helmi M.

Department of Infection Prevention and Control, National Guard Health Affairs,
King Abdulaziz Medical City-King Fahad National Guard Hospital, Riyadh, Saudi
Arabia.

OBJECTIVE: To determine the prevalence of the vaccine-preventable diseases caused
by varicella, measles, rubella, and hepatitis A and B viruses in a multinational 
healthcare workforce. DESIGN: Prospective cohort study. SETTING: A 750-bed
tertiary care center located in Riyadh, Saudi Arabia. METHODS: In compliance with
hospital policy, newly recruited healthcare workers (HCWs) were enrolled in the
study from September 2001 to March 2005. Serum samples were collected from all
HCWs during the initial hiring process and tested for IgG antibodies against each
of the 5 viral agents. Nonimmune HCWs were subsequently vaccinated at the
earliest opportunity. RESULTS: A total of 4,006 newly hired (international and
local) employees were included in the study. All underwent serologic testing for 
IgG antibodies against varicella, measles, rubella, hepatitis A, and hepatitis B 
viruses. Of the total, 63% were female and 37% were male. Middle Eastern
employees comprised 47% of the total, followed by employees from the Far East
(35%), the West (10%), and Africa (8%). Forty-two percent were nurses, 27% were
in administration, 18% were medical technicians, and 13% were physicians. Among
the 4,006 newly hired HCWs, 14% had negative IgG antibody test results for
varicella virus, 13% for measles virus, 10% for rubella virus, 33% for hepatitis 
A virus, and 43% for hepatitis B virus. More women than men were susceptible to
hepatitis A (40% vs. 24%; P<.001), whereas more men were susceptible to hepatitis
B (55% vs. 35%; P<.001). Varicella susceptibility was more common among HCWs from
the Far East (19%), whereas susceptibility to measles, rubella, hepatitis A, and 
hepatitis B was highest among HCWs from the Middle East. Both relative youth and 
male sex were associated with lack of antibodies against hepatitis B virus and
rubella virus. In contrast, female sex and younger age were associated with lack 
of antibodies against hepatitis A virus (P<.001). CONCLUSION: Seroprevalence
surveys of vaccine-preventable diseases among HCWs, although labor intensive, are
invaluable in caring for a multinational workforce.

PMID: 17080374 [PubMed - indexed for MEDLINE]

185: Arch Pathol Lab Med. 2006 Nov;130(11):1680-3.

Molecular detection of transfusion transmitted virus coinfection with some
hepatotropic viruses.

Zaki Mel-S, el-Hady NA.

Mansoura University, Faculty of Medicine, Department of Clinical Pathology,
Mansoura 65 Egypt. May_s65@hotmail.com

CONTEXT: A novel human DNA virus was isolated from the serum of a patient with
posttransfusion hepatitis; it was named transfusion transmitted virus (TTV).
OBJECTIVE: To ascertain the influence of TTV (detected by polymerase chain
reaction amplification of a conserved region of the viral genome) coinfection in 
individuals infected with hepatitis viruses (A, B, and C) and to investigate the 
putative role played by TTV in hepatic dysfunction in individuals with acute
non-A-E hepatitis. DESIGN: Sixty-two patients with viral hepatitis were included 
in the study in addition to 18 blood donors. Viral study of 4 hepatotropic
viruses (A, B, C, and E) was carried out. Study for TTV DNA was performed by
nested polymerase chain reaction. RESULTS: The prevalence of TTV was not
statistically different between hepatitis patients and blood donors, and it was
not correlated to the levels of the hepatic aspartate aminotransferase and
alanine aminotransferase between individuals evidencing dual infection with
hepatitis B and C viruses and healthy blood donors. However, in the group of
patients with viral hepatitis of unknown etiology (non-A-E), those evidencing TTV
viremia had statistically significant lower levels of alanine aminotransferase (P
= .03) and aspartate aminotransferase (P = .04) than those who were TTV negative.
CONCLUSIONS: We can conclude that TTV is a frequent virus isolated from patients 
with various types of viral hepatitis, from cases of hepatitis without obvious
viral agent, and from the healthy population. TTV has no effect on biochemical
markers of associated viral hepatitis. It may be associated with a mild form of
non-A-E hepatitis.

PMID: 17076531 [PubMed - indexed for MEDLINE]

186: World J Gastroenterol. 2006 Oct 14;12(38):6212-5.

Relationship between antioxidant capacity and oxidative stress in children with
acute hepatitis A.

Cemek M, Dede S, Bayiroglu F, Caksen H, Cemek F, Mert N.

Faculty of Science, Afyon Kocatepe University, Afyon, Turkey. mcemek@yahoo.com

AIM: To investigate in children with acute hepatitis A. According to our
knowledge, there are no data about the blood levels of malondialdehyde (MDA, an
indicator of oxidative stress) and nonenzymic antioxidants in children with acute
hepatitis A. METHODS: Whole blood MDA and reduced glutathione (GSH), serum
beta-carotene, retinol, vitamin E and vitamin C levels were studied in 19 (10
females, 9 males) children with acute hepatitis A and in 29 (13 females, 16
males) healthy control subjects. RESULTS: There was a statistically significant
difference between patients and controls for all parameters (P < 0.05). Lipid
peroxidation marker MDA was significantly elevated (P < 0.001), while
antioxidants beta-carotene, retinol and GSH were significantly decreased (all P <
0.001) in patients compared to healthy subjects. In addition, alpha-tocopherol
and ascorbic acid levels were significantly lower in patients when compared to
age and sex matched controls (P < 0.05, P < 0.01, respectively). CONCLUSION: Our 
study shows that hepatitis A virus induces oxidative stress in children with
hepatitis A. This finding could be taken into consideration to improve the
therapeutic approach in acute hepatitis A.

PMID: 17036398 [PubMed - indexed for MEDLINE]

187: J Hepatol. 2006 Dec;45(6):770-8. Epub 2006 Sep 22.

Hepatitis A virus infection suppresses hepatitis C virus replication and may lead
to clearance of HCV.

Deterding K, Tegtmeyer B, Cornberg M, Hadem J, Potthoff A, Böker KH, Tillmann HL,
Manns MP, Wedemeyer H.

Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical
School, Carl-Neuberg Str.1, 30625 Hannover, Germany.

BACKGROUND/AIMS: The significance of hepatitis A virus (HAV) super-infection in
patients with chronic hepatitis C had been a matter of debate. While some studies
suggested an incidence of fulminant hepatitis A of up to 35%, this could not be
confirmed by others. METHODS: We identified 17 anti-HCV-positive patients with
acute hepatitis A from a cohort of 3170 anti-HCV-positive patients recruited at a
single center over a period of 12 years. RESULTS: Importantly, none of the
anti-HCV-positive patients had a fulminant course of hepatitis A. HCV-RNA was
detected by PCR in 84% of the anti-HCV-positive/anti-HAV-IgM-negative patients
but only in 65% of anti-HCV-positive patients with acute hepatitis A (p=0.03),
indicating suppression of HCV replication during hepatitis A. Previous HAV
infection had no effect on HCV replication. After recovery from hepatitis A, an
increased HCV replication could be demonstrated for 6 out of 9 patients with
serial quantitative HCV-RNA values available while 2 patients remained HCV-RNA
negative after clearance of HAV throughout follow-up of at least 2 years.
CONCLUSIONS: HAV super-infection is associated with decreased HCV-RNA replication
which may lead to recovery from HCV in some individuals. Fulminant hepatitis A is
not frequent in patients with chronic hepatitis C recruited at a tertiary
referral center.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17034895 [PubMed - indexed for MEDLINE]

188: Saudi Med J. 2006 Oct;27(10):1515-22.

Prevalence of anti-hepatitis B and anti-hepatitis A antibodies among school aged 
children in Western Saudi Arabia.

Jaber SM.

Department of Pediatrics, King Abdul-Aziz University Hospital, PO Box 80205,
Jeddah 21589, Kingdom of Saudi Arabia. soad@farsijewelry.com

OBJECTIVE: To determine the seroprevalence of antibodies to hepatitis B virus
(HBV) and hepatitis A virus (HAV) among children in Jeddah, Kingdom of Saudi
Arabia (KSA) and to evaluate the need of anti-HAV mass vaccination. METHODS: This
study was carried out on random samples of schools located at different regions
in Jeddah, KSA during the year 2004. A total of 527 sera, (285 males and 242
females), collected from children aged (4-14 years) were tested for
anti-hepatitis B surface (antigen) (HBsAb) and anti-HAV viruses antibodies by
enzyme linked immunosorbent assay technique. RESULTS: Approximately 98% of
children received HBV while 49% of received HAV vaccine. For HBV the overall
seropositivity was 75% while HAV was 28.7%, whereas seronegativity was 14% for
HBV and 70.5% for HAV. Percentage of seropositivity against HBV was elevated in
vaccinated versus non-vaccinated children (p < 0.000). In vaccinated children
against HBV, percentage of seropositivity was elevated in children attending
public versus those attending private and no schools (p < 0.000) and in Saudi
versus non-Saudi children (p < 0.05). In vaccinated and non-vaccinated children
against HAV, percentage of seropositivity was elevated in children attending
public versus those attending private schools (p < 0.000) and no schools (p <
0.000) and in males (p < 0.05) versus females (p < 0.01). In vaccinated children,
percentage of seropositivity for HBV obtained by age range from 4-6 years was
78.7%, for 7-11 years 74.4% and for 12-14 years 72.6%, whereas for HAV virus,
seropositivity was 14.8% for 4-6 years, 38.3% for 7-11 years and 28.6% for 12-14 
years. CONCLUSION: Despite successful coverage of mass vaccination against HBV
among school aged children, in Jeddah, KSA, there are high prevalence levels of
seronegative with increasing age suggesting outbreak of disease among adolescent.
Low prevalence of protective antibodies against HAV in vaccinated and
non-vaccinated children may suggest application of mass vaccination program.

PMID: 17013474 [PubMed - indexed for MEDLINE]

189: J Virol Methods. 2006 Dec;138(1-2):109-16. Epub 2006 Sep 26.

Hepatitis A in Tunisia: phylogenetic analysis of hepatitis A virus from 2001 to
2004.

Gharbi-Khelifi H, Ferre V, Sdiri K, Berthome M, Fki L, Harrath R, Billaudel S,
Aouni M.

Laboratoire des Maladies Transmissibles et Substances Biologiquement Actives,
Faculté de Pharmacie de Monastir, rue Avicenne, 5000 Monastir, Tunisia.

Tunisia is a highly endemic area for hepatitis A virus (HAV) infection. In the
present study, the phylogenetic characterization of the VP1 gene (882
nucleotides) and of the VP1/2A junction (336 nucleotides) of Tunisian strains
were examined. One hundred strains isolated from patient with anti-HAV IgM from
2001 to 2004 were amplified by RT-PCR, sequenced at the VP1 and at the VP1/2A
junction and aligned with the published sequences to establish phylogenetic
analysis. All Tunisian strains belong to genotype I with a greater presence of
sub-genotype IA (98%) originate from most of Tunisian regions and 2% of
sub-genotype IB. In addition, sub-genotype IA and IB strains formed 25 different 
clusters. Genetically similar strains were also identified between 2001 and 2004 
isolated from the southern and the central part of Tunisia, suggesting that an
indigenous strain has been circulating in the Tunisia. The genetic profile of the
VP1 region showed that Tun159-02 and Tun40-03 clustered respectively in the IB
and IA sub-genotype, however, analysis of VP1/2A junction revealed in contrast
that Tun159-02 and Tun40-03 clustered respectively in IA and IB. This is the
first report to identify sub-genotype IA in Tunisia and provides new data on the 
genetic relatedness of HAV from Tunisia and the distribution of sub-genotype IA
in this part of the world.

PMID: 17005259 [PubMed - indexed for MEDLINE]

190: Epidemiol Infect. 2007 May;135(4):549-54. Epub 2006 Sep 26.

Hepatitis A virus infection in people of South Asian origin in England and Wales:
analysis of laboratory reports between 1992 and 2004.

Gungabissoon U, Andrews N, Crowcroft NS.

Health Protection Agency Centre for Infections, London, UK.

The aim of the study was to determine whether rates of hepatitis A infection are 
higher in people of South Asian origin compared to the general population, to
look for evidence of spread to the general population, and to identify ways to
improve preventive strategies. Routine laboratory reports of hepatitis A
infection in England and Wales in 1992-2004 were analysed. Study participants
were patients with confirmed hepatitis A infection reported to the Health
Protection Agency by the diagnosing laboratory. Nam Pehchan software was used to 
identify patients of South Asian ethnicity. Main outcome measures were comparison
of incidence of hepatitis A in South Asian and non-South Asian groups, by age and
region. Rates of infection were significantly higher in the South Asian group
compared to the non-South Asian group (rate ratio 2.68, 95% confidence interval
2.07-3.47). Patients in the South Asian group had a younger age distribution.
Travel was an important risk factor with 85% of those of South Asian origin
acquiring their infection abroad, most frequently in the Indian subcontinent,
compared to less than one third of those in other groups. Health-care
professionals should ensure that all travellers to high-risk countries are
protected by hepatitis A vaccination. Targeted information campaigns may be
indicated in regions of the United Kingdom for people in South Asian minority
ethnic groups.

Publication Types: 
    Clinical Trial
    Comparative Study

PMID: 16999877 [PubMed - indexed for MEDLINE]

191: J Med Virol. 2006 Nov;78(11):1392-7.

Co-circulation of genotype IA and new variant IB hepatitis A virus in outbreaks
of acute hepatitis in Hungary--2003/2004.

Reuter G, Juhász A, Kosztolányi L, Lefler E, Fekete Z.

Regional Laboratory of Virology, Department of Epidemiology, ANTSZ Baranya County
Institute of State Public Health Service, Pécs, Hungary. reuterg@baranya.antsz.hu

Hepatitis A virus (HAV) is one of the most important causes of acute infectious
hepatitis worldwide. In Hungary, the reported number of HAV infections has been
decreasing in the last four decades, nevertheless, still, each year 500-800 new
cases and multiple outbreaks occur, particularly in the northeast region of
Hungary. In Hungary, serology is used routinely to establish the diagnosis of HAV
infection without genetic analysis of HAV strains for molecular epidemiology. In 
this study, serum samples collected from symptomatic patients were tested by
enzyme-immunoassay (anti-HAV-IgM ELISA) to establish the cause of three acute
hepatitis A outbreaks (outbreak 1--from low prevalence region in Southwest
Hungary in 2003 and outbreaks 2 and 3 from the endemic region in Northeast
Hungary in 2004). Outbreak strains were characterized by reverse
transcription-polymerase chain reaction (RT-PCR) amplification of a 360 bp viral 
VP1/2A region, amplicon sequencing and phylogenetic analysis. Four, seven, and
three sera from outbreaks 1, 2, and 3, respectively, were investigated by RT-PCR 
for HAV genome and HAV RNA was detected in 4 (100%), 4 (57%), and 2 (67%)
samples. All strains belonged to genotype I HAV. Outbreak 1 was caused by the new
variant subtype IB and outbreaks 2 and 3 caused by genetically identical subtype 
IA strains. The Hungarian IA and IB hepatitis A viruses had the highest
nucleotide identity, 98.4% and 99.0%, to IT-SCH-00 and IT-MAR-02 strains,
respectively, detected in year 2000 and 2002 in Italy. Endemic subtype IA and
probably imported new variant subtype IB HAV viruses was detected in outbreaks of
hepatitis in Hungary that are closely related genetically to HAV strains in
Italy.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16998889 [PubMed - indexed for MEDLINE]

192: J Med Virol. 2006 Nov;78(11):1398-405.

High and persistent excretion of hepatitis A virus in immunocompetent patients.

Tjon GM, Coutinho RA, van den Hoek A, Esman S, Wijkmans CJ, Hoebe CJ, Wolters B, 
Swaan C, Geskus RB, Dukers N, Bruisten SM.

Department of Infectious Diseases, Public Health Service of Amsterdam, 1000 CE,
Amsterdam, The Netherlands.

The duration and level of virus excretion in blood and faeces of patients with
hepatitis A virus (HAV) infection were studied in relation to levels of alanine
aminotransferase (ALT), disease severity and HAV genotype. Clinical data, blood
and faeces were collected from 27 patients with acute hepatitis A (median age: 33
years) for a maximum of 26 weeks. Single blood donations from 55 other patients
with acute HAV (median age: 32 years) were also used. Virus loads were quantified
by competitive nested RT-PCR. HAV was excreted in faeces for a median period of
81 days after disease onset, with 50% of patients still excreting high levels at 
Day 36 (2 x 10(6) - 2 x 10(8) copies/ml faeces suspension). Viraemia was
detected, but not quantifiable, for a median period of 42 days. In the first 10
days of illness, higher ALT levels were correlated with higher viraemia levels.
Comparison of patients infected with genotype 1a with those infected with type 1b
did not differ significantly in terms of the duration of HAV excretion or
jaundice. In conclusion, faecal excretion of HAV is at a high titre in the first 
month, perhaps making patients infectious for a longer period than assumed
currently. Blood banks should be aware that viraemia may be present for more than
1 month, and genotype did not affect the duration of virus excretion or jaundice.

PMID: 16998883 [PubMed - indexed for MEDLINE]

193: Curr Top Microbiol Immunol. 2006;304:95-114.

Universal mass vaccination against hepatitis A.

André FE.

feandre@yahoo.com

When first introduced in 1992 the hepatitis A vaccine was recommended for
individuals at high risk of exposure. This policy was not expected to have a
significant impact on disease incidence at population level in view of the
epidemiology of the hepatitis A virus (HAV). More recently two countries, Israel 
and Bahrain, and regions or subpopulations in others (Australia, China,
Byelorussia, Italy, Spain, US) have embarked upon more ambitious vaccination
programmes that aim to immunize whole birth cohorts. After a brief survey of the 
virology and epidemiology of HAV, the disease burden it inflicts and a short
history of the development of HAV vaccines--both live (in China) and killed
vaccines are available--he vaccination programmes introduced in the countries
mentioned above are described. The results have been spectacular: disease
incidence, not only in the vaccinated cohorts but also in the whole population,
have plummeted within a few years of the start of mass vaccination. There is now 
convincing evidence that the vaccine confers herd immunity if the main spreaders 
of the virus are targeted for immunization. This finding should encourage other
countries to start mass vaccination programmes against HAV, particularly as
pharmacoeconomic studies are beginning to show that such a strategy could be a
cost-effective way of controlling the disease. It is now even conceivable to
eradicate HAV. In fact, this should be easier to achieve than polio eradication
as HAV vaccines confer more durable immunity than polio vaccines. However, the
global disease burden of HAV is generally thought not to be high enough to
justify such an undertaking in the foreseeable future.

Publication Types: 
    Review

PMID: 16989266 [PubMed - indexed for MEDLINE]

194: Salud Publica Mex. 2005 Nov-Dec;47(6):396-401.

Hepatitis A: the burden among Latino children in California.

Hayes-Bautista DE, Hsu P, Pérez A, Sosa L, Gamboa C.

Center for the Study of Latino Health and Culture, Department of General Internal
Medicine and Health Services Research, UCLA School of Medicine, Los Angeles,
California 90024, USA. dhayesb@ucla.edu

OBJECTIVE: To determine the prevalence of Hepatitis A within subpopulations of
southern California counties. MATERIAL AND METHODS: Age and race/ethnic-specific 
hepatitis A rates were derived from the California Department of Health Services 
Surveillance and Statistics Section for 1996-2001 and from demographic data of
the California Department of Finance. RESULTS: 2.3 million Latino children (aged 
0-14 years) in five southern California counties had a rate of 31.1 cases per
100,000, five times higher than the non-Hispanic white rate. CONCLUSION: The CDC 
Advisory Committee on Immunization Practices recommends routine vaccination for
children with "very high" rates of hepatitis A. The annual prevalence of
hepatitis A in California, especially in southern California, met the CDC's "very
high" definition, therefore Latino children in these counties should be
considered for routine childhood hepatitis A vaccination. As health has no
borders, this issue should be addressed by the public health services of both,
the United States' and Mexico's public health services.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16983984 [PubMed - indexed for MEDLINE]

195: Mem Inst Oswaldo Cruz. 2006 Jun;101(4):423-6.

Prevalence of hepatitis A virus infection in Goiânia, Goiás, Brazil, by molecular
and serological procedures, 1995-2002.

Fiaccadori FS, Soares CM, Borges AM, Cardoso DD.

Laboratório de Virologia, Instituto de Patologia Tropical e Saúde Pública,
Goiânia, Brazil.

In this study, a total of 865 serum samples were collected between 1995 and 2002 
from individuals living in Goiânia, Central Brazil, and clinically suspected of
hepatitis. After exclusion of 162 samples which were positive for hepatitis B
virus or hepatitis C virus, 703 samples were tested for anti-hepatitis A virus
(anti-HAV) IgM antibodies by enzyme immunoassay. In addition, 588 of these
samples and 22 fecal samples were analyzed by reverse transcription-nested PCR
for HAV RNA detection, with positivity indices of 13.1% (77/588) and 54.5%
(12/22), respectively. A similar index of viral RNA detection in anti-HAV-IgM
positive or negative samples was observed in serum samples. HAV infection is a
public health problem worldwide and this study underscores the extent of HAV
circulation in our region.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16951814 [PubMed - indexed for MEDLINE]

196: Mem Inst Oswaldo Cruz. 2006 Jun;101(4):401-5.

Early infection and asymptomatic spread of hepatitis A virus in a public child
care center in Rio de Janeiro, Brazil: should attending children under two years 
of age be vaccinated?

Morais LM, de Paula VS, Arantes MR, Oliveira ML, Gaspar AM.

Departamento de Virologia, Instituto Oswaldo, Fiocruz, Rio de Janeiro, RJ,
21045-900, Brasil. moraislm@ioc.fiocruz.br

A cross-sectional study was conducted in order to identify hepatitis A virus
(HAV) serological markers in 418 individuals (mean age, 16.4 years; range, 1
month-80 years) at a public child care center in Rio de Janeiro, Brazil, as well 
as to analyze risk factors and determine circulating genotypes. Serum samples
were tested using an enzyme immunoassay. Reverse transcription polymerase chain
reaction (RT-PCR) was used to detect and characterize HAV RNA, and sequencing was
performed. Anti-HAV antibodies and IgM anti-HAV antibodies were detected,
respectively, in 89.5% (374/418) and 10.5% (44/418) of the individuals tested.
Acute HAV infection in children was independently correlated with crawling (p <
0.05). In 56.8% (25/44) of the IgM anti-HAV-positive individuals and in 33.3%
(5/15) of the IgM anti-HAV-negative individuals presenting clinical symptoms, HAV
RNA was detected. Phylogenetic analysis revealed co-circulation of subgenotypes
IA and IB in 93.3% (28/30) of the amplified samples. In present study, we verify 
that 79% (30/38) of children IgM anti-HAV-positive were asymptomatic. In child
care centers, this asymptomatic spread is a more serious problem, promoting the
infection of young children, who rarely show signs of infection. Therefore,
vaccinating children below the age of two might prevent the asymptomatic spread
of hepatitis A.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16951811 [PubMed - indexed for MEDLINE]

197: Vaccine. 2007 Jan 5;25(3):446-9. Epub 2006 Aug 17.

Long-term immunogenicity after single and booster dose of a live attenuated
hepatitis A vaccine: results from 8-year follow-up.

Wang XY, Xu ZY, Ma JC, von Seidlein L, Zhang Y, Hao ZY, Han OP, Zhang YL, Tian
MY, Ouyang PY, Zhang ZY, Han CQ, Xing ZC, Chen JC.

International Vaccine Institute, San 4-8 Bongcheon-7-dong, Kwanak-gu, Seoul
151-818, Republic of Korea. xywang@ivi.int

Live, attenuated hepatitis A vaccines are used widely in China but there is
uncertainty regarding the persistence of vaccine-induced anti-HAV antibodies
after single dose and booster dose administrated at month 12. A large scale
clinical trial to evaluate the live, attenuated hepatitis A vaccine was conducted
in Hebei province between 1996 and 1999. Five years after the trials, children in
single dose and booster dose groups were bled and followed. Seventy two percent
(61/85) of children who received a single trial dose had detectable anti-HAV
antibodies for 96 months (GMC at 96 months: 89.0 mIU/mL). In the booster group
98% (48/49) children remained anti-HAV positive with GMC of 262.8 mIU/mL at month
96. The reinjection with live attenuated HAV vaccine can elicit a booster effect.
Results from single dose group seems not to support the need for booster doses of
live attenuated hepatitis A vaccine in immunocompetent individuals regarding the 
persisting anti-HAV and anamnestic response of a single dose vaccine. Continued
monitoring of anti-HAV antibodies is needed for a rational hepatitis A
immunization strategy in China.

Publication Types: 
    Randomized Controlled Trial

PMID: 16949710 [PubMed - indexed for MEDLINE]

198: Curr Opin Infect Dis. 2006 Oct;19(5):456-9.

Vaccination against hepatitis A and B: developments, deployment and delusions.

Zuckerman JN.

Academic Centre for Travel Medicine & Vaccines and the WHO Collaborating Centre
for Reference, Research & Training in Travel Medicine, Royal Free & University
College Medical School, London, UK. j.zuckerman@medsch.ucl.ac.uk

PURPOSE OF REVIEW: Current issues in immunization against hepatitis A and B are
discussed, including the need to abandon risk-based approaches in favour of
universal vaccination, the use of combined hepatitis A and B vaccines and
multivalent vaccines, the development of third-generation triple antigen
hepatitis B vaccines and polyvalent vaccines. RECENT FINDINGS: The emergence of
hepatitis B surface antigen mutants remains a concern in diagnostic work and
immunoprophylaxis and horizontal transmission of the G145R variant stresses the
need for surveillance programmes. The more recent and unfounded concerns about
the safety of hepatitis B vaccines are noted. Innovative approaches to vaccine
production including DNA vaccines and the expression of hepatitis B antigen
components in plants (edible vaccines) are reviewed. SUMMARY: This review
describes further evidence to support the introduction of universal immunization 
against hepatitis B in those countries where this has yet to be implemented.
Immunization programmes will continue to evolve to include the administration of 
polyvalent vaccines in order to best protect populations against infectious
diseases.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 16940869 [PubMed - indexed for MEDLINE]

199: World J Gastroenterol. 2006 Aug 7;12(29):4683-8.

Virological course of hepatitis A virus as determined by real time RT-PCR:
Correlation with biochemical, immunological and genotypic profiles.

Hussain Z, Das BC, Husain SA, Polipalli SK, Ahmed T, Begum N, Medhi S, Verghese
A, Raish M, Theamboonlers A, Poovorawan Y, Kar P.

Room No. 111, Department of Medicine, Maulana Azad Medical College, New Delhi
110002, India. hussainzahep@gmail.com

AIM: To undertake analysis of hepatitis A viral load, alanine aminotransferase
(ALT), and viral genotypes with duration of viremia, and to correlate these
parameters with CD4(+)/ CD8(+) lymphocyte populations that control cell-mediated 
immunity. METHODS: Cell counts were carried out using fresh whole blood collected
in EDTA vials using a fluorescence activated cell sorter. Hepatitis A virus (HAV)
RNA was extracted from blood serum, reverse transcribed into cDNA and quantified 
by Real-Time polymerase chain reaction and was genotyped. RESULTS: Among 11
patients, 10 could be analyzed completely. Of these, 3 had severe acute hepatitis
(s-AH) and the remainder had a self-limited acute hepatitis A (AHA), with one
patient with fulminant disease (encephalopathy Grade IV) dying on the 4th d. The 
ALT level was significantly higher both in AHA (1070.9 +/- 894.3; P = 0.0014) and
s-AH (1713.9 +/- 886.3; P = 0.001) compared to normal controls (23.6 +/- 7.2).
The prothrombin time in s-AH patients (21.0 +/- 2.0; P = 0.02) was significantly 
higher than in AHA (14.3 +/- 1.1; P = 0.44). The CD4(+)/CD8(+) ratio in AHA
patients (1.17 +/- 0.11; P = 0.22) and s-AH (0.83 +/- 0.12; P = 0.0002) were
lower than seen in normal healthy controls (1.52). Self-limited cases had peak
viral load at the beginning of analysis while in s-AH patients this occurred at
the 15th or 30th d. In acute and severe groups, one patient each belonged to
genotype IA, with the remaining 8 cases belonging to genotype IIIA. The only
fulminant hepatic failure case belonged to genotype IA. HAV viral load and ALT
values collected during the entire course of the self-limited infection were
directly correlated but this was not the case for s-AH patients. CONCLUSION:
Based on a small-scale study, the persistently higher viral load of s-AH might be
due to diminished cellular immunity and hemolysis. The duration of viremia was
dependent on the host, as the viral genotype had no apparent role in clinical
outcome of AVH and s-AH cases.

Publication Types: 
    Comparative Study

PMID: 16937439 [PubMed - indexed for MEDLINE]

200: J Gastroenterol Hepatol. 2006 Oct;21(10):1615-21.

Association between hepatitis A virus and Helicobacter pylori in a developing
country: the saga continues.

Bizri AR, Nuwayhid IA, Hamadeh GN, Steitieh SW, Choukair AM, Musharrafieh UM.

Department of Internal Medicine, Division of Infectious Diseases, Faculty of
Medicine, American University of Beirut, Beirut, Lebanon.

BACKGROUND: The epidemiologic association between Helicobacter pylori and
hepatitis A virus (HAV) has been evaluated by various different groups with
conflicting conclusions. The aim of the present study was to determine the
prevalence of HAV and H. pylori infection among adolescents attending high
schools in Lebanon, and to identify the sociodemographic factors associated with 
their prevalence, individually and concurrently. METHODS: Nine hundred and two
school students 14-18 years of age were selected randomly from 30 schools
scattered all over Lebanon and tested for IgG antibodies against hepatitis A and 
H. pylori. Each student received a copy of a self-administered questionnaire to
be completed by his/her parents inquiring about demographics, history of
immunization, and prior viral hepatitis illness in the student. Bivariate
analysis examined the association between different sociodemographic variables
and prior HAV or H. pylori infection, and multivariate regression analysis was
done to determine the factors independently associated with prior infection.
RESULTS: Using ELISA the seroprevalence of antibodies against HAV was 71.3% as
compared to 61.6% for anti-H. pylori. A total of 9.1% of those tested were
negative for both agents. A multinomial regression analysis revealed that place
of residence in relation to district or urban versus rural areas, in addition to 
mothers' education, were important determinants for the incidence of both agents.
CONCLUSION: The low number of subjects negative for both H. pylori and HAV
antibodies in Lebanon is indicative of their high prevalence in the country. It
is possible that this high prevalence reflects an age-specific prevalence rather 
than a true association.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16928226 [PubMed - indexed for MEDLINE]

201: Vaccine. 2007 Jan 2;25(1):102-8. Epub 2006 Jul 28.

Hepatitis A vaccination of Argentinean infants: comparison of two vaccination
schedules.

López EL, Contrini MM, Xifró MC, Cattaneo MA, Zambrano B, Dumas R, Rouyrre N,
Weber F.

Hospital de Niños Ricardo Gutiérrez, Guido 2676, Piso 10, 1425 Buenos Aires,
Argentina. eduardoluislopez@fibertel.com.ar

BACKGROUND: Early immunization to protect infants against hepatitis A (HA) is
recommended in intermediate or high endemic areas of the world, but little is
known of the effects of maternal antibodies on the immune response. We studied
the immunogenicity and reactogenicity of an inactivated HA vaccine administered
in two different schedules to 2-month-old infants in an intermediate/high endemic
area in Argentina. METHODS: In this double-blind, randomized study 131 infants
received either three doses (at 2, 4, 6 months of age [Group A]) or one dose (at 
6 months of age [Group B]) of the pediatric inactivated HA vaccine, Avaxim 80,
and a booster dose at 15-18 months. HAV antibodies were measured (ELISA) at 2, 7,
15-18 and 16-19 months of age. Immediate (30 min after injection) and solicited
local and systemic reactions were recorded for 7 days after each injection.
RESULTS: Of 107/131 subjects (81.6%) who completed the study and who provided
final serum samples after booster dose, 94 (87.8%) were seropositive at enrolment
(>20 mIU/mL) with geometric mean concentrations (GMC) of 2989 and 3637 mIU/mL in 
Groups A and B, respectively. One month post-booster GMCs were 8236 mIU/ml (95%
CI; 6304, 10760) and 1687 mIU/ml (1148, 2479) in Groups A and B, respectively,
with 100% seroprotection. CONCLUSIONS: The HA vaccine was well tolerated and
induced immunological priming in both groups during the first year of life in
spite of the presence of maternal antibodies. Post-booster GMCs achieved after
one or three primary doses suggest a long-term protection against HA.

Publication Types: 
    Clinical Trial, Phase II
    Comparative Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 16914234 [PubMed - indexed for MEDLINE]

202: J Gastroenterol Hepatol. 2006 Sep;21(9):1435-8.

Molecular epidemiology of hepatitis A virus in Brazilian Amazon.

De Paula VS, Niel C, Teves SC, Villar LM, Virgolino H, Gaspar AM.

Department of Virology, Oswaldo Cruz Institute, Rio de Janeiro, Brazil.
vdepaula@ioc.fiocruz.br

BACKGROUND: Hepatitis A virus (HAV) is highly endemic in the Amazon. However, few
data are available regarding HAV genotypes circulating in this region of the
world. The aim of the present study was to characterize genetically HAV isolates 
circulating in the Brazilian part of the Amazon. METHODS: Blood samples were
collected from 134 IgM anti-HAV positive patients (sporadic cases). Viral RNA was
extracted and the virion protein (VP)1/2A junction region of the HAV genome was
successfully amplified by reverse transcription-polymerase chain reaction for 81 
samples (60.4%). Nucleotide sequences (210 bp) of the 81 isolates were
determined. RESULTS: All HAV samples were from genotype I, with 78 (96.3%)
belonging to subgenotype IA and three (3.7%) to subgenotype IB. By phylogenetic
analysis, it was shown that 72/78 of the subgenotype IA isolates formed a cluster
separated from the other South American HAV isolates previously characterized.
CONCLUSION: The present study provides valuable new data on the genetic
relatedness of HAV from the Amazon. Subgenotype IB circulates in the Brazilian
Amazon but the predominant genotype is 1A, similar to what occurs in most South
American countries.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16911689 [PubMed - indexed for MEDLINE]

203: J Environ Health. 2006 Jul-Aug;69(1):16-8, 24, 26.

Hepatitis A in a food worker and subsequent prophylaxis of restaurant patrons.

Patnaik JL, Dippold L, Vogt RL.

Tri-County Health Department, Greenwood Village, CO 80111, USA. jpatnaik@tchd.prg

A laboratory-confirmed case of hepatitis A was reported to Tri-County Health
Department (TCHD) in Colorado, and the infected person was subsequently
determined to have been a food worker at a local restaurant during the period of 
infectiousness. After conducting a public health risk assessment, TCHD decided to
offer immune globulin (IG) to potentially exposed restaurant patrons. A two-day
clinic in Adams County, Colorado, administered IG to 693 individuals. Planning,
implementation, and evaluation of this clinic used a total of 900 staff hours and
had a financial cost of dollar48,300. No additional restaurant employees became
ill, and no secondary cases of hepatitis A were reported within the community.
The mass-prophylaxis clinic was an important public health measure taken to
prevent the potential spread of illness. The experience also provided relevant
hands-on emergency-preparedness training that can be applied in other settings.

PMID: 16910104 [PubMed - indexed for MEDLINE]

204: Indian J Med Res. 2006 Jun;123(6):760-9.

Comment in:
    Indian J Med Res. 2006 Jun;123(6):727-9.    Indian J Med Res. 2006 Oct;124(4):451-2.

Molecular characterization of hepatitis A virus from a large outbreak from
Kerala, India.

Arankalle VA, Sarada Devi KL, Lole KS, Shenoy KT, Verma V, Haneephabi M.

National Institute of Virology, Pune, India. varankalle@yahoo.com

BACKGROUND & OBJECTIVES: Hepatitis A is highly prevalent in India and mainly
presents as a sporadic disease. This study investigated an outbreak of viral
hepatitis at Medical College Hospital area, Kottayam, Kerala state, India during 
January 2005. METHODS: Blood (133), faecal (1), sewage (4), and water samples
(13) were collected. Sera were tested for IgG- and IgM-anti-HAV and IgM
antibodies against hepatitis E (IgM-anti-HEV). Sewage, faeces and water samples
were tested for HAV RNA in nested RT-PCR and HAV RNA positive samples were
further processed for RNA quantitation using Real Time PCR. RESULTS: Of the 1180 
total cases, 540 were reported from Medical college area. Two deaths were
reported among doctors. Patients from the community gave a previous history of
visit to medical college hospital area. The sewage treatment plant at the campus 
was non-functional since 1990 and the untreated sewage was constantly overflowing
and getting mixed with a canal. At the time of the study, all the water sources
were superchlorinated. HAV RNA was present in the faeces of hepatitis A patient
(1.36 x 10(7) copies/ml), sewage tank (2.57 x 10(3) copies/ml and the canal (<100
copies/ml). None of the 13 water samples concentrated 10,000-fold and the soil
sample showed presence of HAV RNA. Phylogenetic analysis based on 5'-non-coding
and P2 regions showed HAV-genotype IIIA in all samples. INTERPRETATION &
CONCLUSION: The aetiological agent of the present outbreak was found to be HAV.
Epidemic hepatitis A (genotype-IIIA) is emerging in Indian adults, emphasizing
the need for definite policy for control.

PMID: 16885597 [PubMed - indexed for MEDLINE]

205: J Travel Med. 2006 Jul-Aug;13(4):219-26.

Hepatitis A, typhoid and malaria among travelers--surveillance data from Québec
(Canada).

Provost S, Gagnon S, Lonergan G, Bui YG, Labbé AC.

Direction de santé publique des Laurentides, Institut national de santé publique 
du Quebec, Canada. sprovost@santepub-mtl.qc.ca

Analysis of epidemiological data on health problems related to international
travel helps put into perspective preventive interventions for travelers. To
document the epidemiological context of travel health interventions in Québec, we
reviewed surveillance data for three infectious diseases. The analysis included
data collected in the notifiable diseases surveillance system for hepatitis A,
typhoid, and malaria cases reported from 2000 to 2002. Additional data were
obtained from the provincial hepatitis risk factor database as well as from
regional public health departments. More than 40% of cases of hepatitis A for
which risk factor information is available are associated with international
travel; 20% of these cases were contracted in Mexico and 22% in the West Indies. 
The risk of acquiring hepatitis A seems to be higher among travelers under 35
years of age; also, given the number of Quebecers traveling to all regions of the
world, this risk is proportionally higher in Africa. Data gathered for typhoid
indicate that the risk to travelers from Québec is proportionately higher for
Quebecers traveling to the Indian subcontinent and whose purpose is to visit
family and friends, and for those who stay abroad for 4 weeks or longer. The risk
of malaria is greater in Africa (where contracted cases are mostly caused by
Plasmodium falciparum). Over half of malaria cases involve individuals traveling 
abroad for business (including volunteerism), and almost 75% contracted the
disease during a stay of a month or more. Nearly half of the cases had not taken 
chemoprophylaxis. Available data have limitations for infectious disease
surveillance among Québec travelers: imprecise number of cases (underdiagnosis
and underreporting), imprecise denominators (number of travelers), and lack of
data on the characteristics of trips taken. However, despite its limitations,
this profile of infectious diseases among travelers from Québec provides
interesting data for preventive intervention.

PMID: 16884404 [PubMed - indexed for MEDLINE]

206: J Travel Med. 2006 Jul-Aug;13(4):212-8.

Comment in:
    J Travel Med. 2007 Jan-Feb;14(1):74; author reply 75.

Immunity to hepatitis A and hepatitis B in Indian and Chinese immigrants seen in 
a travel clinic in Massachusetts, United States.

Ooi WW, Gallagher A, Chen LH.

Tufts University School of Medicine, Department of Medicine, Boston, MA, USA.
winnie.w.ooi@lahey.org

Immigrants to the United States from developing countries have a higher
probability of previous infection with hepatitis A virus (HAV) and/or hepatitis B
virus in their countries of origin. Prior knowledge of hepatitis A and B
seroprevalence in this population may aid in determining the need for pretravel
immunizations when these individuals travel to endemic regions. We conducted a
retrospective analysis of hepatitis A and B serologies in a travel clinic
population (from March 1999 through September 2002) to determine the
seroprevalence in our predominantly highly educated foreign-born subjects. All
our patients who had immigrated from China and India and who were older than 60
years (born on or before 1940) were immune to hepatitis A. The Indian and Chinese
subjects who were anti-HAV positive were also significantly older than the
anti-HAV negative group. In addition, in our Indian study group, the hepatitis
A-seropositive individuals first left India at a significantly older age than the
hepatitis A-seronegative group (mean age 22.7 years vs 11.4 years, p < 0.05). Our
small sample size of Chinese subjects may not have permitted a statistically
significant difference to be detected for hepatitis A seroprevalence and age at
departure from their country of origin. These results have helped tailor our
recommendations for pretravel immunizations for our groups of foreign-born
individuals planning to visit endemic areas. Individuals born in China or India
on or before 1940 are likely to have preexisting antibody to hepatitis A and
probably do not need the vaccine when they travel. Younger individuals may elect 
to have a hepatitis A antibody titer checked before getting the vaccine.

PMID: 16884403 [PubMed - indexed for MEDLINE]

207: Braz J Med Biol Res. 2006 Jul;39(7):873-81.

Co-circulation of genotypes IA and IB of hepatitis A virus in Northeast Brazil.

Villar LM, Morais LM, Aloise R, Melo MM, Calado IA, Lampe E, Gaspar AM.

Departamento de Virologia, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, RJ,
Brasil. lvillar@ioc.fiocruz.br

The Northeast region is the location of most cases of acute hepatitis A virus
(HAV) in Brazil. In the present study, the genotypes of HAV strains from
Pernambuco State, one of most populous states in the Northeast region, were
characterized. Blood samples positive for anti-HAV IgM from 145 individuals (mean
age = 29.1 years), collected during 2002 and 2003, were submitted to nested
RT-PCR for amplification of the 5'non-translated region (5'NTR) and VP1/2A
regions of the HAV genome. The VP1/2A and 5'NTR regions were amplified in 39 and 
21% of the samples, respectively. Nucleotide sequencing was carried out in 46% of
VP1/2A and in 53% of 5'NTR isolates. The identity in nucleotide sequence of the
VP1/2A region ranged from 93.6 to 100.0%. Phylogenetic analysis of the VP1/2A
sequences showed that 65% belong to sub-genotype IA and 35% to sub-genotype IB.
Co-circulation of both sub-genotypes was observed in the two years studied.
Distinct clusters of highly related sequences were observed in both
sub-genotypes, suggesting endemic circulation of HAV strains in this area. In the
5'NTR isolates, 92.7-99.2% identity was observed and two isolates presented one
deletion at position 413. Phylogenetic analysis showed that genotype IA strains
cluster in the tree in the same way as genotype IB strains, but one IIIA isolate 
from Spain clusters with genotype IB strains. These results do not allow us to
state that 5'NTR could be used to genotype HAV sequences. This is the first
report of co-circulation of sub-genotypes IA and IB in this region, providing
additional information about the molecular epidemiology of HAV strains in Brazil.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16862277 [PubMed - indexed for MEDLINE]

208: Eur J Epidemiol. 2006;21(7):545-9. Epub 2006 Jul 21.

Prevalence of hepatitis and HIV infections and vaccination rates in patients
entering the heroin-assisted treatment in Switzerland between 1994 and 2002.

Gerlich M, Gschwend P, Uchtenhagen A, Krämer A, Rehm J.

Research Institute for Public Health and Addiction, Konradstrasse 32, CH-8031,
Zürich, Switzerland. miriam.gerlich@isgf.unizh.ch

BACKGROUND: Hepatitis C virus (HCV) remains very prevalent in injection drug
users (IDUs). In spite of recommended vaccinations against hepatitis A virus
(HAV) and hepatitis B virus (HBV), many IDUs remain susceptible to HAV and HBV.
STUDY POPULATION AND METHODS: Patients entering heroin-assisted treatment between
2000 and 2002 (N = 210) were compared for infectious disease status with patients
entering this treatment in 1998 (N = 243) and between 1994 and 1996 (N = 1035).
Infection status was determined with the aid of questionnaires and blood tests
for antibodies against HAV, HBV core antigen, HCV and HIV. RESULTS: In the cohort
2000-2002 78.3% of the patients were HCV positive, 53.3% were HBV positive, 41.2%
were HAV positive and 12.6% were HIV positive. In comparison to the cohorts
entering the heroin- assisted treatment at an earlier time, there was a
significant reduction of HBV and HAV infections, but not of HCV and HIV
infections. 15.6% of the patients entering between 2000 and 2002 were vaccinated 
against HBV and 10.3% against HAV. 31.1% of patients at entrance were susceptible
for HBV and 48.5% for HAV. In comparison to patients entering treatment in 1998
there was no significant increase in patients who were vaccinated against HBV.
CONCLUSIONS: This data illustrates the need for improving HCV prevention and more
consequent vaccination against HBV and HAV in IDUs.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16858622 [PubMed - indexed for MEDLINE]

209: Epidemiol Infect. 2007 Apr;135(3):402-8. Epub 2006 Jul 19.

Marked decrease in the incidence and prevalence of hepatitis A in the Basque
Country, Spain, 1986-2004.

Cilla G, Pérez-Trallero E, Artieda J, Serrano-Bengoechea E, Montes M, Vicente D.

Servicio de Microbiología, Hospital Donostia, and Departamento de Medicina
Preventiva y Salud Pública, Facultad de Medicina, Universidad del País Vasco, San
Sebastián, Spain.

The aim of this study was to determine changes in the epidemiology of hepatitis A
virus (HAV) infection in the Basque Country, Spain, and to evaluate their
implications for vaccination strategies. A total of 1356 persons were enrolled in
a study of the prevalence of anti-HAV in 2004 and compared with two previous
studies (1986-1987 and 1992). The selection method and the characteristics of the
population were similar in the three studies. A marked decline in the
seroprevalence in all age groups (P<0.001) and in the incidence of cases/100,000 
inhabitants (from 38.0 in 1986-1988 to 2.9 in 2002-2004) were observed. The mean 
age of patients with hepatitis A increased from 17.7 years in 1986-1992 to 21.2
years in 1993-1998 and 25.3 years in 1999-2004 (P<0.001). Between 1997 and 2004, 
20% of patients were hospitalized. The changes observed have occurred rapidly
causing a change in the epidemiological pattern from middle-high endemicity
(1986) to low endemicity (2004).

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16848926 [PubMed - indexed for MEDLINE]

210: Turk J Pediatr. 2006 Apr-Jun;48(2):135-9.

Evaluation of association between hepatitis A and Helicobacter pylori infections 
and routes of transmission.

Egemen A, Yilmaz O, Akil I, Altuğlu I.

Department of Pediatrics, Ege University Faculty of Medicine, Izmir, Turkey.

Previous research about coexistence of Helicobacter pylori (HP) and hepatitis A
virus (HAV) infections and the factors that increase their prevalence has
suggested that the route of transmission of HP infection includes oral-oral and
water-foods as well as the fecal-oral route. The aim of this study was to
evaluate the routes of transmission of HP by comparing the seroprevalences of HP 
and HAV in children. One hundred and two children aged 1-18 years living in rural
and urban regions of Izmir were included in this study. Anti-HP IgG and anti-HAV 
IgG antibodies were measured via enzyme immunoassay method. Seropositivities for 
HP and HAV were 56.8% and 51.9%, respectively. Seroprevalence for both infections
increased with increasing age. However, a significant difference could not be
detected between rural and urban areas. Sex did not have a significant effect.
There was no infection in 22.1% of children, while 30.8% had both of the
infections. 21.1% were positive only for HAV while 26% were positive only for HP.
No significant correlation between seroprevalences of HP and HAV was detected.
This study suggests the existence of various other routes of transmission of HP
apart from the fecal-oral route.

PMID: 16848113 [PubMed - indexed for MEDLINE]

211: Am Fam Physician. 2006 Jun 15;73(12):2162-8.

Hepatitis A.

Brundage SC, Fitzpatrick AN.

South Carolina Department of Health and Environmental Control, Columbia, South
Carolina, USA.

The introduction of hepatitis A vaccines in 1995 led to a drop in the number of
reported cases of hepatitis A and a shift to a higher percentage of cases
occurring in older age groups. The hepatitis A virus survives for extended
periods in the environment. Transmission primarily is fecal-oral, although there 
have been rare instances of transmission through blood products. The virus
appears sporadically and is spread by close personal contact, with occasional
food-borne outbreaks. Older persons infected by the virus usually develop a
symptomatic infection with abrupt onset, fever, and jaundice lasting two months. 
Children usually have an asymptomatic infection and rarely develop jaundice.
Laboratory diagnosis is made by detection of antihepatitis A virus immunoglobulin
M in serum. Ten to 20 percent of symptomatic patients experience a prolonged or
relapsing course of illness, but chronic infection has not been reported.
Fulminant infection occurs in less than 1 percent of patients and can result in
emergent liver transplant or death. Prevention starts with thorough handwashing
and careful food handling. Prompt disease reporting, the identification of
exposed persons, and expeditious administration of immune globulin prevent
secondary transmission of the disease. Physicians should consider routine
vaccination of children 12 to 23 months of age based on recommendations from the 
Centers for Disease Control and Prevention. Vaccination for children two years or
older and adults should be included in routine preventive care for those at
increased risk of contracting the disease (e.g., travelers to certain countries, 
men who have sex with men, drug abusers, recipients of clotting factor
replacement) and for persons with chronic liver disease.

Publication Types: 
    Review

PMID: 16848078 [PubMed - indexed for MEDLINE]

212: Ann Epidemiol. 2006 Nov;16(11):812-9. Epub 2006 Jul 12.

Estimated incidence of hepatitis A virus infection in Catalonia.

Oviedo M, Muñoz MP, Domínguez A, Carmona G.

Epidemiological Surveillance Unit, Generalitat of Catalonia, Spain.

PURPOSE: Hepatitis A normally is underreported by statutory disease reporting
systems. The objective of this study is to estimate the incidence of hepatitis A 
virus (HAV) infection from prevalence surveys of infection carried out in
representative samples of the population in 1989, 1996, and 2002 and the reported
disease incidence during 1991 to 2003 in Catalonia. METHODS: The real incidence
of the infection was estimated from the reported incidence adjusted by the
prevalence of susceptible individuals and the probability of presenting clinical 
manifestations. The bootstrap resampling technique was used to calculate 95%
confidence intervals (CIs) of reported, clinical, and all infection cases.
RESULTS: The infection rate estimated by the bootstrap method was 31.1/100,000
person-years (bootstrap studentized 95% CI, 19.4-56.0), and the rate of clinical 
hepatitis was 20.0/100,000 person-years (95% CI, 11.8-39.9), rates that were 6.3 
and 4.1 times greater than the reported rate during the same period,
respectively. CONCLUSIONS: In children younger than 5 years, the estimated
infection rate was 13.8 times greater than the reported rate. Combined use of
reported cases and results of seroprevalence surveys suggest that underreporting 
of HAV infection is substantial in Catalonia, especially in children younger than
5 years.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16843008 [PubMed - indexed for MEDLINE]

213: Mem Inst Oswaldo Cruz. 2006 Mar;101(2):119-27.

Epidemiological pattern and mortality rates for hepatitis A in Brazil,
1980-2002--a review.

Vitral CL, Gaspar AM, Souto FJ.

Departamento de Virologia, Instituto Oswaldo Cruz-Fiocruz, Av. Brasil 4365,
21040-900 Rio de Janeiro, RJ, Brasil. clvitral@ioc.fiocruz.br

The prevalence of hepatitis A virus (HAV) infection is high in developing
countries, in which low standards of sanitation promote the transmission of the
virus. In Latin America, which is considered an area of high HAV endemicity, most
HAV-positive individuals are infected in early childhood However recent studies
have shown that prevalence rates are decreasing. Herein, we review the data on
HAV prevalence and outbreaks available in scientific databases. We also use
official government data in order to evaluate mortality rates in Brazil over the 
last two decades. Studies conducted in the northernmost regions of Brazil have
indicated that, although improved hygiene has led to a reduction in childhood
exposure to HAV, the greatest exposure still occurs early in life. In the
Southeastern region, the persistence of circulating HAV has generated outbreaks
among individuals of low socioeconomic status, despite adequate sanitation.
Nationwide, hepatitis A mortality rates declined progressively from 1980 to 2002.
During that period, mortality rates in the Northern region consistently exceeded 
the mean national rate and those for other regions. Excluding the North, the
rates in all regions were comparable. Nevertheless, the trend toward decline
observed in the South was paralleled by a similar trend in the North.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 16830702 [PubMed - indexed for MEDLINE]

214: Turk J Gastroenterol. 2006 Jun;17(2):148-50.

Hepatitis A and parvovirus B19 infections in an infant with fulminant hepatic
failure.

Ozçay F, Bikmaz YE, Canan O, Ozbek N.

Department of Pediatric Gastroenterology, Başkent University, School of Medicine,
Ankara, Turkey. fozcay@yahoo.com

Acute viral hepatitis with hepatitis A, B, C, D, and E viruses in the etiology of
fulminant hepatic failure either single or in combinations has been described.
Parvovirus B19 is also an etiologic agent of acute liver failure and
hepatitis-associated aplastic anemia. We present a patient diagnosed with
fulminant hepatitis A referred for liver transplantation. Parvovirus B19
superinfection was detected when the patient developed anemia during the course
of the disease. We discuss possible roles of both viruses in fulminant hepatitis 
and pure red cell aplasia.

Publication Types: 
    Case Reports

PMID: 16830303 [PubMed - indexed for MEDLINE]

215: J Pediatr (Rio J). 2006 Jul;82(3 Suppl):S55-66.

Erratum in:
    J Pediatr (Rio J). 2007 Jan-Feb;83(1):following 97.

Viral hepatitis prevention by immunization.

Ferreira CT, da Silveira TR.

Hospital de Clinicas de Porto Alegre, Universidade Federal do Rio Grande do Sul
(UFRGS), Porto Alegre, RS, Brazil. cristinatarga@terra.com.br

OBJECTIVE: To present an updated review and criticism of viral hepatitis A and B 
prevention by immunization. SOURCES OF DATA: Review of medical articles obtained 
from the MEDLINE database. The most recent and representative articles on the
subject (2000-2006) were selected. The Centers for Disease Control and Prevention
(CDC), American Academy of Pediatrics (AAP), Brazilian Society of Pediatrics and 
Brazilian Ministry of Health websites were also researched. SUMMARY OF THE
FINDINGS: Viral hepatitis prevention is an enormous challenge to the public
health systems of countries and the medical and scientific communities. Hepatitis
viruses produce important morbidity and mortality in the world, causing acute and
chronic hepatic disease. There are highly efficient vaccines available on the
market to prevent new infections by the A and B viruses. However, A and B viruses
continue to be among the most commonly notified diseases preventable by vaccines.
In this article, we discuss the vaccines used to prevent these infections, with
the aim of expanding knowledge and the practice of prevention of these infectious
diseases. CONCLUSIONS: Although the vaccines against A and B hepatitis are
recommended for various risk groups, estimated vaccine coverage is still modest
and many vaccination opportunities are lost. In order to reduce the incidence of 
A and B hepatitis, which are preventable by vaccines, it is necessary for
physicians to encourage their patients to be vaccinated.

Publication Types: 
    Review

PMID: 16826313 [PubMed - indexed for MEDLINE]

216: Gastroenterol Clin Biol. 2006 May;30(5):757-62.

Hepatitis E is an autochthonous disease in industrialized countries. Analysis of 
23 patients in South-West France over a 13-month period and comparison with
hepatitis A.

Péron JM, Mansuy JM, Poirson H, Bureau C, Dupuis E, Alric L, Izopet J, Vinel JP.

Service d'Hépato-Gastro-Entérologie, Fédération Digestive Fédération Digestive,
CHU Toulouse, Hôpital Purpan, Toulouse. peron.jm@chu-toulouse.fr

OBJECTIVES: Hepatitis E virus (HEV) is responsible for acute hepatitis
predominantly in developing countries. In Western Europe and in the US, cases of 
acute HEV infection are uncommon and occur primarily in travelers returning from 
endemic countries. The aim of this study was to describe patients with acute
hepatitis E in South West France and compare them with patients with acute
hepatitis A. METHODS: 23 consecutive patients over 13 months were analysed. Acute
hepatitis E was diagnosed on the presence of specific serum antibodies or viral
RNA detection in serum or stools. Real time PCR products from viraemic patients
were sequenced. RESULTS: All the HEV sequences belonged to genotype 3. Two
patients (8%) died during their hospital stay, both suffered from severe
underlying disease. Only 3 patients (13%) had travelled outside of Europe, within
3 months of the onset of disease. When compared to 23 patients with acute
hepatitis A at the same hospital and during the same time frame, HEV-infected
patients were older (54.4 +/- 16.6 vs 24.5 +/- 16.6, P<0.05), had lower ALT
levels (55.4 X upper normal limit +/- 48.6 vs 107.8 X upper normal limit +/-
82.8, P<0.05) and had lower incidence of recent travel outside of Europe (13% in 
the hepatitis E group vs 60% in the hepatitis A group, P<0.05). CONCLUSIONS:
Hepatitis E can be considered an autochthonous infection in South West France.
All strains sequenced were related to genotype III. When compared to hepatitis A,
HEV-infected patients were older, had lower ALT levels and had a lower incidence 
of travel outside of Europe.

Publication Types: 
    Comparative Study

PMID: 16801899 [PubMed - indexed for MEDLINE]

217: Eur J Public Health. 2007 Feb;17(1):69-74. Epub 2006 Jun 22.

Measurement and reporting of burden of disease for hepatitis A: results of the
EUROHEP.NET feasibility survey.

Bonanni P, Boccalini S, Bechini A; EUROHEP.NET Team.

Department of Public Health, University of Florence, Florence, Italy.
paolo.bonanni@unifi.it

BACKGROUND: European countries use a wide variety of surveillance systems and
prevention measures for viral hepatitis. Each system is adapted to the local
situation and an overview was never mapped out at European level. The EUROHEP.NET
Project is a European Commission-funded feasibility study for a future network on
surveillance and prevention of vaccine-preventable hepatitis. We analysed the
measurement and reporting of burden of disease for hepatitis A (HA) and B (HB) in
the participating countries. METHODS: Twenty-eight countries were invited to
participate in this study. An online survey was available from the project's
website (www.eurohep.net). The questions concerned the organisation of the
surveillance system, case definition, burden of disease, epidemiology, and
vaccination strategies. The responses on data sources and the numeric data
related to burden of disease for HA for the period 1997-2001 were analysed.
RESULTS: Twenty-two countries completed the survey for hepatitis A. Data on total
number of hospitalisations and deaths were available from 17 and 18 countries,
respectively, although sometimes not complete. Data on hospitalisation days,
number of liver transplants and proportion of these due to HAV were often not
available. CONCLUSION: Surveillance systems on burden of disease for hepatitis A 
show a wide diversity among the participating countries. The introduction of a
standardised system of data collection at the European Union level according to
ICD-10 but respecting the local current practices is a primary need, especially
for data that should be collected in all countries, like hospitalisation and
mortality. A link to surveillance databases is also strongly recommended.

PMID: 16793836 [PubMed - indexed for MEDLINE]

218: J Med Virol. 2006 Aug;78(8):1011-4.

Case report: Hepatitis A preceding Guillain-Barré syndrome.

Chitambar SD, Fadnis RS, Joshi MS, Habbu A, Bhatia SG.

National Institute of Virology, Pune, Maharashtra, India. chitambars@hotmail.com

A case of acute hepatitis A with Guillain-Barré Syndrome subtype AMAN (acute
motor axonal neuropathy) in a 17-year-old male is reported. Serum and
cerebrospinal fluid were positive for anti-hepatitis A virus (HAV) IgM, IgG, and 
IgA. The onset of the syndrome was evident in week 3 of illness. The remarkably
high titers of serum anti-HAV IgG appeared unique to a hepatitis A patient with
the syndrome. Phylogenetic analysis of the HAV genome detected in the serum and
feces revealed genotype IIIA, circulating commonly in Pune, western India. 2006
Wiley-Liss, Inc.

Publication Types: 
    Case Reports

PMID: 16789022 [PubMed - indexed for MEDLINE]

219: J Med Virol. 2006 Aug;78(8):1015-24.

Distinct changing profiles of hepatitis A and E virus infection among patients
with acute hepatitis, patients on maintenance hemodialysis and healthy
individuals in Japan.

Mitsui T, Tsukamoto Y, Hirose A, Suzuki S, Yamazaki C, Masuko K, Tsuda F, Endo K,
Takahashi M, Okamoto H.

Masuko Memorial Hospital and Masuko Institute for Medical Research, Nagoya,
Aichi-Ken, Japan.

To compare the epidemiologic profiles of hepatitis A virus (HAV) and hepatitis E 
virus (HEV) infections in Japan, the prevalence of clinical or subclinical HAV
and HEV infections was investigated serologically and molecularly among 128
consecutive patients (age, mean +/- standard deviation, 37.5 +/- 14.7 years) who 
contracted acute hepatitis between 1989 and 2005 in a city hospital, and among
416 hemodialysis patients (60.1 +/- 12.6 years) and 266 medical staff members
(34.6 +/- 11.4 years) at the same hospital, using stored periodic serum samples
collected since the start of hemodialysis or employment, respectively. Between
1989 and 1995, among 93 patients with acute hepatitis, 51 (54.8%) were diagnosed 
with hepatitis A and only one patient with hepatitis E. Between 1996 and 2005,
however, among 35 patients, only 3 (8.6%) were diagnosed with hepatitis A and 2
(5.7%) with hepatitis E. Although subclinical HEV infection was recognized in
four hemodialysis patients (one each in 1979, 1980, 1988, and 2003) and two
medical staff members (1978 and 2003) in previous studies, none of the 191
hemodialysis patients who had been negative for anti-HAV at the start of
hemodialysis contracted HAV infection during the observation period of 7.6 +/-
6.4 years. Only one (0.4%) of the 246 medical staff members who had been negative
for anti-HAV at the start of employment acquired hepatitis A during the
observation period of 7.9 +/- 8.0 years: none had subclinical HAV infection.
Clinical or subclinical HEV infection has occurred rarely during the last three
decades, while HAV infection has markedly decreased at least since 1996. 2006
Wiley-Liss, Inc.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16789007 [PubMed - indexed for MEDLINE]

220: J Food Prot. 2006 Jun;69(6):1468-72.

Green onions: potential mechanism for hepatitis A contamination.

Chancellor DD, Tyagi S, Bazaco MC, Bacvinskas S, Chancellor MB, Dato VM, de
Miguel F.

Department of Urology, School of Medicine, University of Pittsburgh, Pittsburgh, 
Pennsylvania 15213, USA.

The largest documented foodborne hepatitis A outbreak in U.S. history occurred in
November 2003. The source of that outbreak was green onions from a farm in
Mexico. Two biomarkers were used to determine ways in which hepatitis A virus
(HAV) can contaminate onions. Fluorescent microspheres (1.0 to 10 microm) and HAV
vaccine were placed on the soil and the surfaces of pot-grown onions and in the
liquid medium of hydroponically cultivated onions. Reverse transcription PCR
(RT-PCR) was used to identify HAV RNA. Microspheres were found on the outside and
inside of the pot-grown onions for up to 60 days. RT-PCR revealed HAV RNA from
the vaccine in well-washed green onions. In the hydroponically grown onions,
microspheres were found throughout the onion after only 1 day. RT-PCR also
revealed HAV RNA inside the hydroponically grown onions. Both biomarkers support 
the hypothesis that HAV can contaminate the inside of the growing onion and can
be taken up intracellularly through the roots. Once inside, the particles are
impossible to remove by cleaning.

PMID: 16786877 [PubMed - indexed for MEDLINE]

221: J Addict Dis. 2006;25(2):25-32.

Hepatitis and human immunodeficiency virus co-infection among injection drug
users in Los Angeles County, California.

Fisher DG, Reynolds GL, Jaffe A, Perez MJ.

Center for Behavioral Research and Services, California State University, Long
Beach, CA 90813, USA. fisher@csulb.edu

This study examined the prevalence of hepatitis A (HAV), B (HBV), C (HCV), and
Human Immunodeficiency Virus (HIV) co-infection among Injection Drug Users (IDUs)
in Los Angeles County, California, and predictors of multiple infections in this 
population. Six hundred seventy-nine IDUs were recruited from October 2002
through June 2004. Participants completed questionnaires to elicit demographic,
drug and sex risk information, and were tested for hepatitis A, B, C and HIV.A
linear regression model predicting the total number of infections (0 to 4
possible) was constructed. Significant associations were found between HAV and
HBV infection, HAV and HCV infection, and HBV and HCV infection. Predictors of
total co-infections included age of first injection, lifetime years in jail, and 
Hispanic ethnicity. Latinos had the highest proportion of HAV and HBV
co-infection with HCV. The total number of co-infections, especially those
co-infected with all three of the hepatitis infections, was unexpectedly high.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16785216 [PubMed - indexed for MEDLINE]

222: Clin Infect Dis. 2006 Jul 15;43(2):158-64. Epub 2006 Jun 12.

A mathematical model of hepatitis a transmission in the United States indicates
value of universal childhood immunization.

Van Effelterre TP, Zink TK, Hoet BJ, Hausdorff WP, Rosenthal P.

GlaxoSmithKline Biologicals, Rixensart, B-1330, Belgium.
thierry.van-effelterre@gskbio.com

BACKGROUND: US recommendations issued in 1999 for hepatitis A (HA) childhood
immunization varied according to regional HA incidences prior to vaccination.
Mathematical models of HA transmission, especially those accounting for herd
protection, can be useful in formulating new, highly effective recommendations
that could lead to disease elimination. METHODS: A mathematical model of HA
transmission was designed to assess the impact of different vaccination
strategies on the evolution of HA infection over time in the United States. The
model represents HA transmission dynamics and is stratified by age and regions
defined in the Advisory Committee for Immunization Practices 1999
recommendations. The model accounts for herd protection and HA importation, using
an age-dependent "force of infection" varying over time as a function of the
prevalence of subjects with infectious HA. RESULTS: The model predicts a clear
benefit of vaccinating all US children at as young an age as possible. Nationwide
routine immunization at 1 year of age with 70% coverage would prevent 57% of
additional cases during the period 1995-2029, compared with the continuation of
the regional strategy of vaccinating children at 2 years of age, as recommended
by the Advisory Committee for Immunization Practices in 1999. In contrast, the
model also predicts that nationwide routine immunization for children 12 years of
age only would result in a 14% increase of HA cases during the period 1995-2029, 
compared with the number of cases predicted with the regional strategy of the
immunization of 2-year-olds. CONCLUSIONS: These findings highlight the importance
of accounting for herd protection induced by early childhood HA vaccination. They
also support the very recent Advisory Committee for Immunization Practices
recommendations for universal HA immunization of 1-year-olds.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16779741 [PubMed - indexed for MEDLINE]

223: Epidemiol Rev. 2006;28:101-11. Epub 2006 Jun 14.

Hepatitis A in the era of vaccination.

Wasley A, Fiore A, Bell BP.

Division of Viral Hepatitis, National Center for Infectious Diseases, Centers for
Disease Control and Prevention, Atlanta, GA 30333, USA. awasley@cdc.gov

The World Health Organization estimates an annual total of 1.5 million clinical
cases of hepatitis A worldwide, but seroprevalence data indicate that tens of
millions of hepatitis A virus infections occur each year. In the United States in
the 1980s-1990s, an average of 26,000 acute hepatitis A cases were reported per
year, representing approximately 270,000 infections annually. Since licensure of 
effective hepatitis A vaccines in the mid-1990s, US hepatitis A rates have fallen
precipitously-particularly since 1999, when routine childhood vaccination was
recommended in states with consistently elevated rates. By 2004, the overall rate
had declined to 1.9/100,000 population, the lowest rate ever recorded and 79%
lower than any previously recorded nadir. These marked declines occurred with
relatively modest vaccination coverage, suggesting that strong herd immunity
accompanies the initiation of routine vaccination programs. Routine childhood
vaccination has produced similar results in Israel and selected regions of Italy,
Spain, and Australia. Hepatitis A vaccination will probably remain a low priority
for some time in the poorest countries, where most persons are infected as young 
children. However, shifts in the epidemiologic patterns of disease associated
with declining hepatitis A virus transmission are occurring in many regions of
the world. These shifts are likely to create circumstances where strategically
targeted vaccination of children could produce substantial public health
benefits.

Publication Types: 
    Review

PMID: 16775039 [PubMed - indexed for MEDLINE]

224: J Infect. 2007 Feb;54(2):e91-3. Epub 2006 Jun 12.

Unusual cardiac features in cholestatic hepatitis A in an adolescent: improvement
with corticosteroid treatment.

Atabek ME, Pirgon O.

Department of Pediatrics, Faculty of Medicine, Selcuk University, Konya, Turkey. 
meatabek@hotmail.com

Hepatitis A is one of the most frequent infectious liver diseases affecting
children worldwide. Extra-hepatic manifestations of acute hepatitis A virus are
rare in pediatric age group. We report a case of a 16-year-old, otherwise healthy
adolescent who had viral hepatitis A with cardiac manifestations. The patient is 
the first pediatric case of hepatitis A with a combination of hypotension,
persistent bradycardia and progressive cholestasis.

Publication Types: 
    Case Reports

PMID: 16769122 [PubMed - indexed for MEDLINE]

225: Med Princ Pract. 2006;15(4):266-9.

Epidemiology and outcome of severe hepatitis A infection in children in Kuwait.

Husain E, Al-Tawfiq JA, Husain K.

Department of Pediatrics, Infectious Diseases Hospital, Kuwait.
entesar@qualitynet.net

OBJECTIVE: To describe the epidemiology, clinical features and outcome of
hepatitis A virus (HAV) infection in children in Kuwait. SUBJECTS AND METHOD: The
medical records of 350 patients (age 0-16 years) admitted to the Infectious
Diseases Hospital, Kuwait, between January 2000 and December 2002, with hepatitis
A infection were reviewed. RESULTS: The mean age was 8.6 +/- 3.8 years and 47% of
patients were between 7 and 12 years old. Kuwaiti children comprised 44% of
admitted patients. The largest proportion of children with hepatitis A (34%) were
from the northern part of the country. HAV infection was prevalent throughout the
year with a peak during the months of August to October. Of the Kuwaiti children,
31% reported a history of contact with jaundiced patients, while 52% of the
non-Kuwaiti children had a history of recent travel prior to their illness.
Patients had symptoms for a mean of 6 +/- 3.6 days prior to presentation. The
mean length of hospitalization was 5.8 +/- 2.9 days. The rate of complications of
HAV infection was 6% and only one child required admission to the intensive care 
unit for fulminant hepatitis. None of the patients had permanent sequelae.
CONCLUSIONS: HAV infection is a significant cause of morbidity for children in
Kuwait. The disease is mostly prevalent in preschool and school age children.
Despite the excellent outcome of all patients, a considerable number of patients 
tend to have a complicated course and prolonged hospitalization. In view of these
data, hepatitis A vaccine should be considered as a part of routine childhood
immunization in Kuwait. Copyright 2006 S. Karger AG, Basel.

PMID: 16763392 [PubMed - indexed for MEDLINE]

226: Vaccine. 2006 Jul 7;24(27-28):5599-603. Epub 2006 May 11.

Epidemiologic shift in the prevalence of Hepatitis A virus in Saudi Arabia: a
case for routine Hepatitis A vaccination.

Almuneef MA, Memish ZA, Balkhy HH, Qahtani M, Alotaibi B, Hajeer A, Qasim L, Al
Knawy B.

Department of Infection Prevention and Control, King Abdulaziz Medical City-King 
Fahad National Guard Hospital, Riyadh, Saudi Arabia.

This study aims to determine the seroprevalence of Hepatitis A among a selected
group of Saudi children and thus, identify the best immunization strategy. A
school-based seroprevalence study in children 4-18 years of age attending the
National Guard schools was done. Of the 25,531 children attending the National
Guard schools, 2399 (10%) were randomly selected through a stratified one-stage
cluster survey. The overall prevalence of HAV-IgG was 28.9%. The prevalence was
almost the same in male and female (28.2% versus 29.5%, respectively). There was 
a gradual increase in the HAV-IgG with 7% in children (< 8 years), 14% (8-11
years), 30% (12-15 years), and 52% (> 16 years) of age. Since a substantial
proportion of this pediatric population confirms a continuing decrease in
anti-HAV seroconversion rates, we recommend including Hepatitis A in the schedule
of routine childhood vaccinations.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16757065 [PubMed - indexed for MEDLINE]

227: Vaccine. 2006 Jul 17;24(29-30):5684-9. Epub 2006 May 11.

Active immunisation during an outbreak of hepatitis A in a German day-care
centre.

Hauri AM, Fischer E, Fitzenberger J, Uphoff H, Koenig C.

Hesse State Health Office, Wolframstr. 33, 35683 Dillenburg, Germany.
a.hauri@hlpug.hessen.de

During an outbreak in a German day-care centre (DCC) caring for 100 children HAV 
vaccination was recommended for children, employees and household members of
cases. A retrospective cohort study was done to evaluate vaccine uptake and
identify possible risk factors for disease. Between 19 December 2004 and 30
January 2005 eight DCC children and seven household members fulfilled the case
definition, i.e. had clinical hepatitis (14) or were diagnosed with asymptomatic 
HAV infection (1). Following the recommendation to vaccinate, given on 23
December 2004, 66.7% (46/69) of DCC children, 15.8% (29/184) of household members
and 5/5 of employees were vaccinated, and three vaccinated children and two not
vaccinated children fell ill. One of 11 children who received human normal
immunoglobulin (HNIG) and four of 58 children who did not receive HNIG fell ill. 
In households in which the DCC child received HAV vaccine and/or HNIG, seven
(5.6%) of 125 household members fulfilled the case definition. In households of
non-immunised children none of the 59 household members fell ill. We conclude
that, although most vaccinations were administered promptly, they may not have
been timely enough to impact the course of the outbreak.

PMID: 16730103 [PubMed - indexed for MEDLINE]

228: Vaccine. 2006 Jun 19;24(25):5300-10. Epub 2006 May 2.

Mucosal immunization against hepatitis A: antibody responses are enhanced by
co-administration of synthetic oligodeoxynucleotides and a novel cationic lipid.

Mitchell LA, Joseph A, Kedar E, Barenholz Y, Galun E.

Goldyne Savad Gene Therapy Institute, Hadassah Medical Organization, Kiryat Ein
Karem, Jerusalem 91120, Israel. Leah_Bellehsen@yahoo.ca

Hepatitis A caused by hepatitis A virus (HAV) transmitted by the fecal-oral
route, results in considerable morbidity and economic loss. Mucosal immunization 
can be more effective than conventional injection at inducing both local and
systemic immunity to HAV. Here we show that co-administration of killed HAV with 
synthetic oligodeoxynucleotides (ODNs) containing CpG sequences, and a novel
polycationic sphingolipid (CCS)/cholesterol liposomal delivery system, markedly
enhances the HAV-specific antibody response at the intestinal interface,
particularly when delivered intrarectally or intranasally, to Balb/c mice at low 
HAV doses. A mucosally delivered, antigen-sparing HAV vaccine that is easily
administered without specialized equipment or personnel, is an attractive
alternative for facilitating mass immunization in hepatitis A outbreaks.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16714070 [PubMed - indexed for MEDLINE]

229: East Afr Med J. 2006 Feb;83(2):86-90.

Hepatitis A seroepidemiology in Eastern Turkey.

Vancelik S, Guraksin A, Alp H.

Department of Public Health, Atatürk University, School of Medicine,
Erzurum-Turkey.

BACKGROUND: It has been reported that there are great deal of changes in the
epidemiology of hepatitis A at the present. The epidemiologic studies regarding
to hepatitis A virus (HAV) infection are not sufficient both in the country and
study region. OBJECTIVE: To investigate HAV seroprevalence and association with
socio-demographic variables. DESIGN: Cross-sectional and community based study.
SETTING: Erzurum Province, Eastern Turkey between April and June 1998. SUBJECTS: 
Four hundred and fifty persons under the age of 30 years. RESULTS: The rate of
the study involvement was 87.1% (392 persons) and ratio for seropositivity 84.2%.
Although seropositivity is elevated by age, it has been high within the younger
age group. Epidemiological changes could not be interpreted, since the study
results were first for the group of people aged under 30 years. Statistical
significance was found between hepatitis A seroprevalence and age, the number of 
households and localisation of toilet within the house. There was no correlation 
between hepatitis A and sex, jaundice history, family type, tap water
availability in the residential area. CONCLUSION: The frequency of hepatitis A
infection appearance in the region was found out to be high as compared to other 
regions of Turkey.

PMID: 16708879 [PubMed - indexed for MEDLINE]

230: MMWR Recomm Rep. 2006 May 19;55(RR-7):1-23.

Prevention of hepatitis A through active or passive immunization: recommendations
of the Advisory Committee on Immunization Practices (ACIP).

Advisory Committee on Immunization Practices (ACIP), Fiore AE, Wasley A, Bell BP.

Division of Viral Hepatitis, National Center for Infectious Diseases, Atlanta, GA
30333, USA.

Routine vaccination of children is an effective way to reduce hepatitis A
incidence in the United States. Since licensure of hepatitis A vaccine during
1995-1996, the hepatitis A childhood immunization strategy has been implemented
incrementally, starting with the recommendation of the Advisory Committee on
Immunization Practices (ACIP) in 1996 to vaccinate children living in communities
with the highest disease rates and continuing in 1999 with ACIP's recommendations
for vaccination of children living in states, counties, and communities with
consistently elevated hepatitis A rates. These updated recommendations represent 
the final step in the childhood hepatitis A immunization strategy, routine
hepatitis A vaccination of children nationwide. Implementation of these
recommendations will reinforce existing vaccination programs, extend the benefits
associated with hepatitis A vaccination to the rest of the country, and create
the foundation for eventual consideration of elimination of indigenous hepatitis 
A virus transmission. This report updates ACIP's 1999 recommendations concerning 
the prevention of hepatitis A through immunization (CDC. Prevention of hepatitis 
A through active or passive immunization: recommendations of the Advisory
Committee on Immunization Practices [ACIP]. MMWR 1999:48[No. RR-12]:1-37) and
includes 1) new data on the epidemiology of hepatitis A in the era of hepatitis A
vaccination of children in selected U.S. areas, 2) results of analyses of the
economics of nationwide routine vaccination of children, and 3) recommendations
for the routine vaccination of children in the United States. Previous
recommendations for vaccination of persons in groups at increased risk for
hepatitis A or its adverse consequences and recommendations regarding the use of 
immune globulin for protection against hepatitis A are unchanged from the 1999
recommendations.

Publication Types: 
    Practice Guideline

PMID: 16708058 [PubMed - indexed for MEDLINE]

231: Int J Mol Med. 2006 Jun;17(6):1093-9.

Human membrane protein Tim-3 facilitates hepatitis A virus entry into target
cells.

Sui L, Zhang W, Chen Y, Zheng Y, Wan T, Zhang W, Yang Y, Fang G, Mao J, Cao X.

Institute of Immunology, Second Military Medical University, Shanghai, PR China.

In this study, a cellular surface membrane protein of immunoglobulin (Ig)
superfamily (IgSF) was identified from a human dendritic cell (DC) cDNA library
by large-scale random sequencing, which is identical to previously reported Tim-3
(T-cell Ig- and mucin-domain-containing molecule 3). Recent data have suggested
the association of the 281-residue mouse Tim-3 molecule with Th1-related T cell
responses and disease in mice. Human Tim-3 is a 301-residue type I membrane
protein whose extracellular region contains a Cys-rich Ig-like domain and a mucin
domain, the characteristics of Tim proteins. It shows significant homology to
human hepatitis A virus (HAV) cellular receptor-1 (HuHAVcr-1)/Tim-1. Human Tim-3 
mRNA was highly expressed in monocytes or monocyte-derived cells, and the
expression level decreased when DC underwent maturation and activation. There is 
no previous report on the biological functions of human Tim-3, especially the
involvement in virus infection. We demonstrated that HeLa cells, which are
refractory to HAV infection, acquired a limited susceptibility to HAV infection
after stably overexpressing human Tim-3 as confirmed by Western blot analysis
using anti-Tim-3 antibody, but Tim-3-Fc fusion protein had no direct HAV-binding 
activity. The results indicated that human Tim-3 can promote HAV entry into
target cells but itself may not function as a cellular receptor of HAV.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16685421 [PubMed - indexed for MEDLINE]

232: Epidemiol Infect. 2006 Dec;134(6):1299-302. Epub 2006 May 10.

Hepatitis A surveillance in England--how many cases are not reported and does it 
really matter?

Matin N, Grant A, Granerod J, Crowcroft N.

Health Protection Agency (HPA) Centre for Infections (CFI) Immunisation
Department and Public Health Training Scheme, London Deanery, London, UK.
drnashamatin@postmaster.co.uk

Underreporting of hepatitis A infection in England may be high and a number of
outbreaks have occurred undetected by routine surveillance. We evaluated
surveillance of hepatitis A cases by employing capture-recapture analysis on data
from two distinct outbreaks of hepatitis A. The overall reporting of cases of
hepatitis A was 81.7% (95% CI 55.3-95) in the first outbreak in North East
England and reporting through Lab Base was 65.7% (95% CI 42.8-76.4). In the
second outbreak in the East Midlands the overall reporting of hepatitis A cases
was 27.8% (95% CI 19-38.7) and through Lab Base 16.6% (95% CI 11.4-23.1).
Underreporting of hepatitis A cases is high. Public health interventions exist to
prevent and control outbreaks of hepatitis A. The lack of reliable data on
incidence and prevalence hampers effective public health management of this
disease.

PMID: 16684404 [PubMed - indexed for MEDLINE]

233: J Gastroenterol Hepatol. 2006 Apr;21(4):689-93.

Increasing trend of acute hepatitis A in north India: need for identification of 
high-risk population for vaccination.

Hussain Z, Das BC, Husain SA, Murthy NS, Kar P.

PCR Hepatitis Laboratory, Department of Medicine, Maulana Azad Medical College,
New Delhi, India.

BACKGROUND AND AIMS: Hepatitis A (HAV) is endemic in India and most of the
population is infected asymptomatically in early childhood with lifelong
immunity. Because of altered epidemiology and decreasing endemicity, the pattern 
of acute HAV infection is changing from asymptomatic childhood infection to an
increased incidence of symptomatic disease in the 18-40 age group. The aims of
the present study were to assess whether the proportion of adults with acute HAV 
infection has been increasing over the years and to analyze the seroprevalence of
immunoglobulin G (IgG) anti-HAV antibodies in young adults above the age of 15
years as well as in cases of chronic liver disease. METHODS: Sera collected from 
3495 patients with acute (1932) and chronic (1563) liver disease attending the
Medical Outpatient Department of Lok Nayak Hospital during the previous five
years (1999-2003) were tested for various serological markers of acute (HBsAg,
HBcIgM, anti-HCV, HEV-IgM, and HAV-IgM) and chronic (HBsAg, HBcIgG, HBeAg, and
anti-HCV) hepatitis. In addition, 500 normal healthy attendants of the patients
above the age of 15 years were tested for IgG anti-HAV as controls. RESULTS: Of
1932 patients with acute viral hepatitis, 221 (11.4%) were positive for
immunoglobulin M (IgM) anti-HAV. The patients who were IgM anti-HAV negative
included hepatitis B (321 patients), C (39 patients), E (507 patients) and
unclassified (844 patients). Although the frequency of HAV infection among
children had increased (10.6% to 22.0%) in the 5-year period, the frequency of
HAV infection among adults had also increased (3.4% to 12.3%) during the same
period. A total of 300 patients with chronic liver diseases that were
etiologically related to hepatitis B (169), C (73) or dual infection (10) and
alcoholic liver injury (48) were tested for the presence of IgG anti-HAV
antibody; 98% (294/300) were positive for the antibody. CONCLUSIONS: Although
universal vaccination against HAV is not currently indicated, selective
vaccination of the high-risk population, based on their serological evidence of
HAV antibody, would be a rational and cost-effective approach.

PMID: 16677154 [PubMed - indexed for MEDLINE]

234: Vaccine. 2006 Jun 5;24(23):4962-8. Epub 2006 Apr 18.

Effectiveness of a hepatitis A vaccination program for migrant children in
Amsterdam, The Netherlands (1992-2004).

Sonder GJ, Bovée LP, Baayen TD, Coutinho RA, van den Hoek JA.

GGD, Municipal Health Service Amsterdam, Department of Infectious Diseases,
Nieuwe Achtergracht 100, PO Box 2200, 1000 CE Amsterdam, The Netherlands.
gsonder@ggd.amsterdam.nl

OBJECTIVE: To evaluate the impact and effectiveness of risk-group vaccination
against hepatitis A targeted at migrant children living in a country with low
endemicity of hepatitis A. METHODS: Retrospective population based data analysis.
Routinely collected data on hepatitis A incidence in migrant children and other
risk groups in Amsterdam from 1 January 1992 to 2004 were analyzed and related to
exposure, immunity and vaccination coverage in migrant children. RESULTS: The
overall hepatitis A incidence in Amsterdam declined after a pediatric vaccine was
introduced in 1997. This decline was seen in migrant children traveling to
hepatitis A-endemic countries, contacts with hepatitis A patients, primary school
students, injecting drug users, and persons with unknown source of infection, but
not in men who have sex with men (MSM) or in travelers to endemic countries other
than migrant children. CONCLUSION: The hepatitis A vaccination campaigns are
effective: they reduce both import and secondary HAV cases. The campaigns could
be more efficient and cost-effective if the hepatitis B vaccinations currently
given to these groups were replaced by a combined hepatitis A and B vaccine. This
would increase the hepatitis A vaccination coverage considerably and further
reduce the hepatitis A incidence.

PMID: 16675076 [PubMed - indexed for MEDLINE]

235: Int J Clin Pract. 2006 Nov;60(11):1432-6. Epub 2006 May 2.

Prevalence of hepatitis A virus infection among municipal solid-waste workers.

Dounias G, Rachiotis G.

Department of Occupational and Industrial Hygiene, National School of Public
Health, Athens, Greece. gdunias@otenet.gr

A study was conducted among 151 municipal workers (72 solid-waste workers, and 79
workers not exposed to waste). Total antibodies against Hepatitis A virus (HAV)
were measured, and socio-demographic information was collected using a
self-administered questionnaire. Univariate analysis has shown that occupational 
exposure to waste, age, duration of employment and educational status were
significantly associated with the prevalence of anti-HAV(+). Municipal Solid
Waste Workers had a higher prevalence of anti-HAV(+) in comparison with municipal
workers not exposed to waste. Duration of employment was significantly associated
anti-HAV(+). Multivariate analysis revealed an independent association of
anti-HAV(+) with occupational exposure to waste and ageing. Our results suggest a
potential causal role of occupational exposure to waste, in the development of
HAV infection.

PMID: 16669822 [PubMed - indexed for MEDLINE]

236: Clin Infect Dis. 2006 Jun 1;42(11):1536-43. Epub 2006 Apr 26.

Erratum in:
    Clin Infect Dis. 2006 Jul 1;43(1):121.

Clinical and virological improvement of hepatitis B virus-related or hepatitis C 
virus-related chronic hepatitis with concomitant hepatitis A virus infection.

Sagnelli E, Coppola N, Pisaturo M, Pisapia R, Onofrio M, Sagnelli C, Catuogno A, 
Scolastico C, Piccinino F, Filippini P.

Division of Infectious Diseases, Azienda Ospedaliera San Sebastiano, Caserta,
Italy. evangelista.sagnelli@unina2.it

BACKGROUND: We evaluated the clinical and virological characteristics of
hepatitis A virus infection in persons concomitantly infected with hepatitis B
virus (HBV) or hepatitis C virus (HCV). METHODS: We enrolled 21 patients with
acute hepatitis A and chronic hepatitis with no sign of liver cirrhosis, 13
patients who were positive for hepatitis B surface antigen (case B group), 8
patients who were anti-HCV positive (case C group), and 21 patients with acute
hepatitis A without a preexisting liver disease (control A group). Two control
groups of patients with chronic hepatitis B (control B group) or C (control C
group) were also chosen. All control groups were pair-matched by age and sex with
the corresponding case group. RESULTS: Fulminant hepatitis A was never observed, 
and hepatitis A had a severe course in 1 patient in the case B group and in 1
patient in the control A group. Both patients recovered.On admission, HBV DNA was
detected in 1 patient in the case B group (7.7%) and in 13 patients (50%) in the 
control B group; HCV RNA was found in no patient in the case C group and in 16
patients (81.2%) in the control C group. Of 9 patients in the case B group who
were followed up for 6 months, 3 became negative for hepatitis B surface antigen 
and positive for hepatitis B surface antibody, 2 remained positive for hepatitis 
B surface antigen and negative for HBV DNA, and 4 became positive for HBV DNA
with a low viral load [corrected] Of 6 patients in the case C group who were
followed up for 6 months, 3 remained negative for HCV RNA, and 3 had persistently
low viral loads. CONCLUSION: Concomitant hepatitis A was always self-limited,
associated with a marked inhibition of HBV and HCV genomes, and possibly had a
good prognosis for the underlying chronic hepatitis.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16652310 [PubMed - indexed for MEDLINE]

237: Epidemiol Infect. 2006 Dec;134(6):1292-8. Epub 2006 May 2.

Outbreak of hepatitis A in two federal states of Germany: bakery products as
vehicle of infection.

Schenkel K, Bremer V, Grabe C, Van Treeck U, Schreier E, Höhne M, Ammon A, Alpers
K.

Department for Infectious Diseases Epidemiology, Robert Koch-Institut, Berlin,
Germany. schenkelk@rki.de

In April 2004, increased numbers of hepatitis A were noted in six neighbouring
districts in Germany. Exploratory interviews showed that patients had consumed
bakery products from company X where two employees had been diagnosed with
hepatitis A in February. A case-control study of consumption of products of
company X was carried out through telephone interviews. Altogether, 64 cases were
identified. Fifty-two cases and 112 controls aged >or=16 years were included in
the case-control study. In total, 46/52 cases and 37/112 controls had consumed
company X products [odds ratio (OR) 15.5, 95% confidence interval (CI) 6.1-39.7].
Of these, 36/46 cases and 16/37 controls had consumed pastries (OR 4.7, 95% CI
1.8-12.3), 25/46 cases and 12/37 controls had consumed filled doughnuts (OR 2.5, 
95% CI 1.0-6.1). Sequence analysis of the VP1-2A junction region indicated 100%
strain homology between cases and an infected employee of company X. We
recommended reinforcement of hygiene precautions, and consideration of a
prolongation of compulsory work absence after post-exposure vaccination.

PMID: 16650329 [PubMed - indexed for MEDLINE]

238: Acta Medica (Hradec Kralove). 2005;48(3-4):173-5.

Two siblings with fulminant viral hepatitis A: case report.

Yalniz M, Ataseven H, Celebi S, Poyrazoğlu OK, Sirma N, Bahçeitoğlu IH.

Firat University, Department of Gastroenterology, Faculty of Medicine, Turkey.
mehmetyalniz@hotmail.com

Fulminant hepatitis is a rare complication of acute hepatitis A infection.
Nevertheless, the seroepidemiology of the infection is rapidly changing with the 
developing world, rendering more adults susceptible to the infection, in
particular with more severe course. We report here fulminant hepatitis A
infection with a mortal course during an epidemic period in two siblings.
Although it causes a self-limited mild disease, hepatitis A virus may have a
severe course including fulminant hepatitis and may lead to mortality, especially
in older ages. Hence, the risk of hepatitis A virus infection and its
complications should be reduced with measures of immunization and sanitation.

Publication Types: 
    Case Reports

PMID: 16640033 [PubMed - indexed for MEDLINE]

239: Gastroenterology. 2006 Apr;130(4):1129-34.

Acute hepatitis A infection in pregnancy is associated with high rates of
gestational complications and preterm labor.

Elinav E, Ben-Dov IZ, Shapira Y, Daudi N, Adler R, Shouval D, Ackerman Z.

Department of Internal Medicine, Mount Scopus Campus, Hadassah-Hebrew University 
Medical Center, Jerusalem, Israel. eelina97@md.huji.ac.il

BACKGROUND & AIMS: Hepatitis A virus (HAV) infection is the most common cause of 
acute hepatitis but is rarely reported during pregnancy. Our aim was to evaluate 
the impact of acute HAV infection on pregnancy outcome. METHODS: Consecutive
admissions of 79,458 pregnant females during a 25-year period were
retrospectively reviewed. RESULTS: Thirteen cases of second and third trimester
HAV infection were found and evaluated. Nine of the 13 patients (69%) developed
gestational complications, including premature contractions (n = 4), placental
separation (n = 2), premature rupture of membranes (n = 2), and vaginal bleeding 
(n = 1). In 8 of these patients, complications led to preterm labor, at a median 
of 34 gestational weeks (range, 31-37 weeks). Delivery was vaginal in 12 of the
13 cases; fetal distress was noted in a single case, and meconium in amniotic
fluid in 2 cases. Median birth weight was 1778 grams and 3040 grams in preterm
and term deliveries, respectively (P < .05). Child outcome was favorable in all
cases. In 4 cases, neonatal serum HAV RNA levels were measured and found
negative. The presence of fever and hypoalbuminemia were associated with delivery
at an earlier gestational week. There was a positive relation between gestational
week at diagnosis of HAV infection and birth week (r = 0.68, P = .02), suggesting
a causality relationship. All mothers featured full recovery from HAV infection. 
CONCLUSIONS: Acute HAV infection during pregnancy is associated with high risk of
maternal complications and preterm labor. HAV serology and maternal vaccination
during prepregnancy evaluation should be considered in areas of the world in
which susceptible adult populations exist.

PMID: 16618407 [PubMed - indexed for MEDLINE]

240: Clin Lab Sci. 2006 Winter;19(1):12-7.

Hepatitis A prevalence among injection drug users.

Wells R, Fisher D, Fenaughty A, Cagle H, Jaffe A.

Section of Chronic Disease Prevention and Health Promotion, Department of Health 
and Social Services, Juneau, AK, USA.

OBJECTIVE: The purpose of this study was to develop a descriptive model of the
association between injection drug use and hepatitis A (HAV) in a sample of
injection drug users (IDUs). DESIGN: From May 1997 to July 1999, 493 subjects
were administered the NIDA Risk Behavior Assessment (RBA). Participants had blood
drawn; sera were tested for antibodies to HAV, hepatitis B core (HBcAB), and
hepatitis C. The principal method of analysis was logistic regression. SETTING:
The study took place in a community-based field station in Anchorage, Alaska.
PARTICIPANTS: Eligibility was determined using the following criteria: a) age
greater than 17 years, b) possession of picture identification, c) positive
urinalysis for cocaine metabolites, morphine, and/or amphetamines using the
ONTRAK system (Roche Diagnostics), and d) injection drug use in the last six
months as confirmed by presentation of track marks. MAIN OUTCOME MEASURE:
Presence of antibodies to HAV infection. RESULTS: The prevalence of total HAV
antibody in our sample was 33% (161/493). The final multivariate logistic model, 
using positive HAV serostatus as the outcome, included positive HBcAB serostatus 
(OR = 3.43; 95% CI, 2.22-5.30), less than high school education (vs. high school 
or greater education) (OR = 2.05; 95% CI, 1.33-3.17), age (OR = 1.06 (each year);
95% CI, 1.03-1.09), number of days injected heroin in the last 30 days (OR = 1.05
(each day), 95% CI, 1.01-1.08), and race (White vs. all other race/ethnicities)
(OR = 0.49; 95% CI, 0.32-0.75). CONCLUSIONS: A model including both demographic
and drug use variables best describes HAV prevalence in this sample. Findings
suggest that IDUs are targets for interventions focusing on hepatitis
vaccinations and hygiene practices. Further research is needed to understand the 
association of HAV with hepatitis B infection.

Publication Types: 
    Research Support, N.I.H., Extramural

PMID: 16617553 [PubMed - indexed for MEDLINE]

241: J Med Virol. 2006 May;78(5):542-50.

Infection with hepatitis A, B, C, and delta viruses among patients with acute
hepatitis in Mongolia.

Tsatsralt-Od B, Takahashi M, Endo K, Buyankhuu O, Baatarkhuu O, Nishizawa T,
Okamoto H.

Division of Virology, Department of Infection and Immunity, Jichi Medical School,
Tochigi-Ken, Japan.

One hundred ten consecutive patients (60 males and 50 females; age, mean +/-
standard deviation [SD], 22.6 +/- 6.4 years; range 16-48 years) who were
clinically diagnosed with sporadic acute hepatitis between December 2004 and
January 2005 in Ulaanbaatar, Mongolia, were studied. IgM antibodies to hepatitis 
A virus were detected in 18 patients (16.4%), IgM antibodies to hepatitis B core 
(anti-HBc IgM) in 38 patients (34.5%) including two patients with concurrent
hepatitis delta virus (HDV) infection, and hepatitis C virus RNA in nine patients
(8.2%). There were 30 hepatitis B virus (HBV) carriers who had detectable
hepatitis B surface antigen and antibodies to HDV but were negative for anti-HBc 
IgM, suggesting that they acquired type D acute hepatitis due to superinfection
of HDV on a background of chronic HBV infection. None had IgM antibodies to
hepatitis E virus (HEV). Consequently, 16.4, 32.7, 6.4, 1.8, and 27.3% of the
patients were diagnosed as having acute hepatitis of type A, B, C, type B + D
(HBV/HDV coinfection), and type D (superinfection of HDV), respectively. The
cause of hepatitis was not known in the remaining 17 patients (15.5%). All 18 HAV
isolates were genotyped as IA, all 9 HCV isolates were genotyped as 1b, and all
32 HDV isolates were classified into genotype I. The distribution of HBV
genotypes among the 67 HBV isolates was A (1.5%, n = 1) and D (98.5%, n = 66).
The present study indicates that de novo infections of HAV, HBV, HCV, and HDV are
prevalent among young adults in Mongolia. Copyright 2006 Wiley-Liss, Inc.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16555292 [PubMed - indexed for MEDLINE]

242: J Travel Med. 2006 Mar-Apr;13(2):78-83.

Immunogenicity and safety of a virosomal hepatitis A vaccine (Epaxal) in the
elderly.

D'Acremont V, Herzog C, Genton B.

Medical Outpatient Clinic, University Hospital, Lausanne, Switzerland.

BACKGROUND: Protection against hepatitis A virus (HAV) in the elderly is becoming
more important as more senior travelers visit areas of high HAV endemicity, and
less have protective antibodies acquired after natural infection during
childhood. This study assessed the immunogenicity and safety of hepatitis A
vaccine in elderly compared to young adults. METHODS: In this open, uncontrolled 
study, subjects of 18 to 45 years or < or = 50 years of age received two doses of
aluminum-free, virosomal HAV vaccine, Epaxal (Berna Biotech Ltd, formerly Swiss
Serum and Vaccine Institute, Bern, Switzerland) 12 months apart. RESULTS: After
both the basic and the booster doses, geometric mean titers (GMT) for anti-HAV
antibodies were 1.7-fold higher in subjects younger than 45 years compared with
those < or = 50 years of age. The proportional increase in GMT after the booster 
dose, however, was similar in younger and older subjects. Seroprotection (< or = 
20 mIU/mL) rates in the younger and older subjects were 100 and 65%,
respectively, after the first vaccination and 100 and 97%, respectively, after
the booster dose. Systemic and local adverse events were mainly mild and
short-lived. CONCLUSION: These data show that HAV virosomal vaccine (Epaxal) is
well tolerated and immunogenic in elderly subjects. The clinical relevance of
lower seroconversion rates after the primary dose is unknown in this population
of travelers.

Publication Types: 
    Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 16553593 [PubMed - indexed for MEDLINE]

243: Turk J Gastroenterol. 2005 Dec;16(4):217-9.

Immune thrombocytopenic purpura as sole manifestation in a case of acute
hepatitis A.

Tanir G, Aydemir C, Tuygun N, Kaya O, Yarali N.

Department of Pediatric Infectious Diseases Pediatrics, Dr. Sami Ulus Children's 
Hospital, Ankara, Turkey. gonultanir58@yahoo.com

Acute hepatitis due to hepatitis A virus is usually a benign selflimiting disease
during childhood. Although many viral infections such as hepatitis B virus,
Parvovirus, and Epstein-Barr virus are associated with extrahepatic autoimmune
phenomena, such manifestations are rare in patients with acute hepatitis A
infection. Immune thrombocytopenia is a benign, self-limiting disease in
children, responding well to treatment and generally associated with viral
infections. Immune thrombocytopenic purpura is rarely reported as a manifestation
of acute hepatitis A. We report a five-year-old boy with immune thrombocytopenic 
purpura as the sole manifestation of anicteric acute hepatitis A infection. Acute
hepatitis A should be included in the differential diagnosis of immune
thrombocytopenic purpura.

Publication Types: 
    Case Reports

PMID: 16547851 [PubMed - indexed for MEDLINE]

244: Rev Inst Med Trop Sao Paulo. 2006 Jan-Feb;48(1):43-4. Epub 2006 Mar 9.

Anti-hepatitis A virus frequency in adolescents at an outpatient clinic in São
Paulo, Brazil.

Dinelli MI, Fisberg M, Moraes-Pinto MI.

Division of Pediatric Infectious Diseases, Department of Pediatrics, Federal
University of São Paulo, São Paulo, Brazil.

The prevalence of hepatitis A virus (HAV) antibodies was assessed in adolescents 
(age ranging from 10.4 to 19.9 years) at an Adolescent Outpatient Clinic in São
Paulo, Brazil. Anti-HAV was detected in 137 (54.2%) out of 253 individuals. When 
separated into two age groups, anti-HAV frequency was higher in the 15 to 19
year-old group (64%) in comparison to the 10 to 14 year-old group (46%)
(Chi-square test: p = 0.004). These results suggest that adolescents in São Paulo
are at risk of hepatitis A infection and are probably contracting HAV infection
during this age period.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16547579 [PubMed - indexed for MEDLINE]

245: Adv Ther. 2005 Nov-Dec;22(6):578-86.

Hepatitis A: a preventable threat.

Leung AK, Kellner JD, Davies HD.

Department of Pediatrics, University of Calgary, Alberta Children's Hospital,
Calgary, Alberta, Canada.

Hepatitis A is a major public health problem, particularly in the pediatric
population. Although hepatitis A infection does not cause chronic liver disease, 
it is associated with significant morbidity. The virus is transmitted primarily
by person-to-person contact via the fecal-oral route. The infection can be
inapparent, subclinical, anicteric, or icteric. In general, the severity of the
disease is inversely correlated with the age of the child. Occasionally,
fulminant hepatitis, which is associated with a high mortality rate, may result. 
The diagnosis of acute hepatitis A is most commonly made through the detection of
immunoglobulin M (IgM) anti-hepatitis A antibody. Treatment is generally
supportive. General preventive measures include improved standards of hygiene and
sanitation. Universal childhood vaccination is the most effective method for
eradicating hepatitis A and preventing its transmission.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 16510374 [PubMed - indexed for MEDLINE]

246: Fed Regist. 2006 Feb 9;71(27):6677-9.

Microbiology devices; reclassification of hepatitis A virus serological assays.
Final rule.

Food and Drug Administration, HHS.

The Food and Drug Administration (FDA) is issuing a final rule to reclassify
hepatitis A virus (HAV) serological assays from class III (premarket approval)
into class II (special controls). FDA is taking this action after reviewing a
reclassification petition submitted by Beckman Coulter, Inc. Elsewhere in this
issue of the Federal Register, FDA is announcing the availability of the guidance
document entitled "Guidance for Industry and FDA Staff: Class II Special Controls
Guidance Document: Hepatitis A Virus Serological Assays" that will serve as the
class II special control for these devices.

Publication Types: 
    In Vitro

PMID: 16502543 [PubMed - indexed for MEDLINE]

247: J Hosp Infect. 2006 Apr;62(4):414-20. Epub 2006 Feb 20.

The risk of hepatitis A infection among healthcare workers: a review of reported 
outbreaks and sero-epidemiologic studies.

Chodick G, Ashkenazi S, Lerman Y.

Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
hodik_g@mac.org.il

All reports of hepatitis A (HA) outbreaks in healthcare settings published
between 1975 and 2003 were studied to determine the background immunity or
susceptibility of healthcare workers (HCWs) to HA. Twenty-six reports were found.
The number of infected personnel ranged from one to 66 and, in most outbreaks,
nurses accounted for the majority of personnel infected, reflecting high attack
rates reaching 15-41%. In addition, we found 23 sero-epidemiological studies for 
HA among HCWs that had been performed in 13 different countries. Seroprevalence
rates of HCWs with anti-HA antibody ranged between 4% among paramedical workers
in Germany to 88% among hospital maintenance workers in Portugal. Effective
infection control of HA outbreaks in hospitals demands early recognition,
including awareness of atypical presentations of the infection, and strict
adherence to universal infection control measures. Education programmes are of
special importance for HCWs in neonatal, paediatric and intensive care units. The
findings of the current study suggest that a pre-employment screening policy and 
administration of active vaccination to susceptible HCWs, particularly nurses,
should be seriously considered in high-risk settings.

Publication Types: 
    Review

PMID: 16488511 [PubMed - indexed for MEDLINE]

248: Euro Surveill. 2006;11(1):37-9.

Hepatitis A vaccination policy for travellers to Egypt in eight European
countries, 2004.

Ward M, Borgen K, Mazick A, Muehlen M.

National Institute for Public Health and the Environment, Bilthoven, The
Netherlands.

In 2004, an outbreak of hepatitis A occurred in European tourists returning from 
Egypt. The reported hepatitis A attack rates varied considerably between tourists
from different European countries. To determine the reason for this divergence in
attack rates, a survey was undertaken with the following objectives: (a)
documentation of national hepatitis A prevention policies for people travelling
to Egypt and (b) documentation of hepatitis A reporting practices in these
countries. A questionnaire was compiled and distributed to 13 European countries.
All eight of the countries that responded had produced guidelines for the
prevention of travel-associated hepatitis A. Between 2001-2003, 40% (range 4-51) 
of hepatitis A cases reported annually were associated with travel abroad. This
occurred despite the fact that all countries recommended active vaccination with 
hepatitis A vaccine for people travelling to Egypt for holidays. There was no
standard case definition for reporting confirmed cases in the countries that
reported hepatitis A cases. As it is likely that travel-associated infections
will increase as more people take overseas holidays, innovative ways to increase 
the number of travellers who seek and adhere to appropriate medical advice prior 
to travel must be explored. In addition, we recommend the use of the European
Commission case definition for notification of confirmed cases of hepatitis A.

PMID: 16484731 [PubMed - indexed for MEDLINE]

249: South Med J. 2006 Jan;99(1):82-4.

Acute pericarditis and renal failure complicating acute hepatitis A infection.

Beyazit Y, Guven GS, Kekilli M, Koklu S, Yolcu OF, Shorbagi A.

Faculty of Medicine, Department of Internal Medicine, Hacettepe University,
Ankara, Turkey.

Hepatitis A infection may result in acute hepatitis, and rarely, fulminant
hepatitis may ensue. Extrahepatic manifestations of hepatitis A are uncommon. The
authors present the case of a 77-year-old male who had development of acute renal
failure and pericarditis during the clinical course of acute hepatitis A
infection. He died as a result of septic shock on the fifth day of
hospitalization. To the best of our knowledge, this is the first report of both
these rare and serious complications appearing in the same patient.

Publication Types: 
    Case Reports

PMID: 16466128 [PubMed - indexed for MEDLINE]

250: Clin Rev Allergy Immunol. 2006 Feb;30(1):25-9.

Urticaria and hepatitis.

Cribier B.

Clinique Dermatologique, University Hospital, Strasbourg, France.
bernard.cribier@chru-strasbourg.fr

Acute urticaria is commonly observed in the prodromic stage of hepatitis A and B 
infection as well as in hepatitis C infection, although only rare cases have been
published regarding the latter. Urticaria is considered one of the pre-icteric
symptoms of viral hepatitis and is related to immune-complex deposits;
subsequently, it may be associated with arthritis and headache (Caroli's triad). 
The absence of specific presentation of acute urticaria in patients with viral
hepatitis is not surprising because many other viral infections can induce
similar cutaneous symptoms. On the other hand, no convincing evidence exists in
which hepatitis virus infection caused chronic urticaria. Data are lacking for
hepatitis B, but several series and one controlled study showed the absence of a 
link between hepatitis C and chronic urticaria. Systematic hepatitis virus
investigations in patients with chronic urticaria probably are not
cost-effective. Hepatitis B or C can occasionally induce urticarial vasculitis,
but this is probably related more to vasculitis than to true urticaria.

Publication Types: 
    Review

PMID: 16461992 [PubMed - indexed for MEDLINE]

251: Am J Gastroenterol. 2006 Feb;101(2):292-6.

Epidemiology and clinical features of sporadic hepatitis E as compared with
hepatitis A.

Chau TN, Lai ST, Tse C, Ng TK, Leung VK, Lim W, Ng MH.

Department of Medicine and Geriatrics, United Christian Hospital, Hong Kong SAR, 
China.

OBJECTIVES: To compare the epidemiology and clinical features of two enterically 
transmitted hepatitis, namely hepatitis E and hepatitis A. METHODS: We analyzed
clinical features and risk factors of 105 cases of hepatitis A and 24 cases of
hepatitis E admitted in 2002. All patients were tested positive for IgM antibody 
against either hepatitis A virus (HAV) or hepatitis E virus (HEV), and all
patients were tested to be negative for IgM anti-HBV or IgG anti-HCV. RESULTS:
Hepatitis A patients were significantly younger (median age = 27 yr) and most had
a recent history of shellfish consumption, whereas hepatitis E patients were
older (median age = 53 yr) and most had a recent travel history. Whereas
hepatitis A was milder and recovery was uneventful, hepatitis E was more severe, 
associated with significant mortality and frequently complicated by protracted
coagulopathy and cholestasis. CONCLUSIONS: Hepatitis E is a more severe disease
entity as compared with hepatitis A and significant proportion of them are
imported cases from an endemic area.

Publication Types: 
    Comparative Study

PMID: 16454833 [PubMed - indexed for MEDLINE]

252: Clin Infect Dis. 2006 Mar 1;42(5):628-33. Epub 2006 Jan 25.

Active surveillance for acute viral hepatitis in rural villages in the Nile
Delta.

Meky FA, Stoszek SK, Abdel-Hamid M, Selim S, Abdel-Wahab A, Mikhail N, El-Kafrawy
S, El-Daly M, Abdel-Aziz F, Sharaf S, Mohamed MK, Engle RE, Emerson SU, Purcell
RH, Fix AD, Strickland GT.

Department of Community, Environmental and Occupational Medicine, Ain Shams
University, Cairo, Egypt.

BACKGROUND: Acute viral hepatitis is less frequent in Egypt than serum antibody
levels suggest. Because acute viral hepatitis has a wide clinical spectrum, we
tested the hypothesis that many cases are undetected because of mild illness
caused by initial, early-childhood exposure to hepatitis viruses. METHODS: During
active case detection among 20,000 inhabitants of rural villages in Egypt, we
screened 1715 symptomatic patients for serum alanine aminotransferase (ALT)
levels. Viral hepatitis markers were tested in 47 subjects who had ALT levels
that were least twice the normal level. RESULTS: Of the 47 individuals tested, 4 
children aged 3-5 years had immunoglobulin M (IgM) antibodies to hepatitis A
virus (anti-HAV IgM). One also had a possible false-positive result to a test for
IgM antibodies to hepatitis E virus. None had serological evidence of acute
hepatitis B virus (HBV) infection or hepatitis C virus (HCV) infection. However, 
33 of the remaining 43 had active HCV infection, having both antibodies to HCV
(anti-HCV) and HCV RNA. Four others anti-HCV without HCV RNA, and 2 others had
seroconversion to anti-HCV during follow-up. Two patients who were positive for
hepatitis B surface antigen had chronic HBV infection. Only 3 with elevated ALT
levels had no evidence of acute or chronic infections with known hepatitis
viruses. Immunoglobulin G antibodies to hepatitis E virus was detected in 40
patients. CONCLUSION: Active surveillance covering approximately 50,000
person-years detected only 4 cases of acute HAV infection. Almost all persons
with mild symptoms and elevated ALT levels had serological evidence of chronic
viral hepatitis, most often associated with HCV. Many of these cases were
probably "flare-ups" of HCV infection or incidental illness in patients with
chronic HCV infection, but some could have been caused by difficult-to-confirm
initial HCV infections. Although serological evidence for exposures was highly
prevalent, hepatitis viruses seldom caused acute viral hepatitis in these
communities.

Publication Types: 
    Research Support, N.I.H., Extramural

PMID: 16447107 [PubMed - indexed for MEDLINE]

253: J Coll Physicians Surg Pak. 2006 Jan;16(1):15-8.

Hepatitis A virus infection -- shifting epidemiology.

Waheed-uz-Zaman Tariq, Hussain AB, Hussain T, Anwar M, Ghani E, Asad-ullah.

Department of Virology, Armed Forces Institute of Pathology, Rawalpindi.
waheedzt@hotmail.com

OBJECTIVE OF THE STUDY: To determine the age distribution in HAV infection and
seasonal variations in the prevalence of acute viral hepatitis caused by
hepatitis A virus. STUDY DESIGN: A descriptive study. PLACE AND DURATION: The
study was carried out on the patients reporting at Virology Department, Armed
Forces Institute of Pathology (AFIP), Rawalpindi, for determination of hepatitis 
A virus (HAV) IgM antibody, from July 2003 to June 2004. PATIENTS AND METHODS:
Altogether 626 patients with clinical suspicion of hepatitis A virus infection
were referred to AFIP Rawalpindi for this test. Blood samples were collected and 
sera were separated and transferred to plastic aliquots that were stored at -20
degrees C in a retrievable fashion until utilized in testing. The testing for
ant-HAV IgM was carried out with the help of a commercial Enzyme Linked
Immunosorbant Assay (ELISA) using reagent kits of DiasSorin (Germany) for HAV IgM
antibodies. RESULTS: The HAV IgM positive rate was 40.57% (252/626). Those tested
included the sporadic cases as well as the patients from outbreak in two schools 
of Nowshera cantonment. The age of patients testing positive for HAV IgM, ranged 
from 03 to 27 years. There was a statistically significant seasonal difference in
rate of positivity in different months of the calendar year. An outbreak of HAV
infection was seen in the children of two neighboring schools of a cantonment, in
which 44 children in different classes developed clinical jaundice. CONCLUSION:
HAV infection occurs in a significant proportion of young people with a clinical 
suspicion of HAV infection. There is a changing trend of developing hepatitis A
in the age beyond 18 years and in outbreaks, which was not there in our patients 
previously due to universal immunity found against HAV by the age of 18. It was
because of chances of consumption of polluted food.

PMID: 16441981 [PubMed - indexed for MEDLINE]

254: Vaccine. 2006 Apr 5;24(15):2702-9. Epub 2006 Jan 6.

Hepatitis vaccination among drug users.

Quaglio G, Lugoboni F, Mezzelani P, Des Jarlais DC, Lechi A.

Medical Service for Addictive Disorders, Department of Internal Medicine,
University of Verona, Policlinico GB Rossi, 37134 Verona, Italy.
gianluca.quaglio@azosp.vr.it

Hepatitis virus infections are traditionally a major health problem among drug
users (DUs). Several factors may favor the rapid spread of hepatitis infection in
this category of patients. HBV and HCV are easily transmitted through exposure to
infected blood and body fluids. DUs often prepare and use drug solutions
together. Many in the DU community are infected and this provides multiple
opportunities for transmission to others. Many of these patients with chronic
hepatitis virus infection are not aware of their infections and this facilitates 
the spread of the diseases. Viral hepatitis is not inevitable for DUs. Although
multiple factors have prevented the development of vaccines for hepatitis C, both
hepatitis A and hepatitis B can be prevented by immunization. The purpose of this
overview is to summarize and discuss the hepatitis vaccination in this
population.

Publication Types: 
    Review

PMID: 16436307 [PubMed - indexed for MEDLINE]

255: Epidemiol Infect. 2006 Aug;134(4):808-13. Epub 2006 Jan 25.

Seroepidemiology of hepatitis A and hepatitis B virus in Luxembourg.

Mossong J, Putz L, Patiny S, Schneider F.

Laboratoire National de Santé, LuxembourgCRP-Santé, Luxembourg.
joel.mossong@lns.etat.lu

A prospective seroepidemiological survey was carried out in Luxembourg in
2000-2001 to determine the antibody status of the Luxembourg population against
hepatitis A virus (HAV) and hepatitis B virus (HBV). One of the objectives of
this survey was to assess the impact of the hepatitis B vaccination programme,
which started in May 1996 and included a catch-up campaign for all adolescents
aged 12-15 years. Venous blood from 2679 individuals was screened for the
presence of antibodies to HAV antigen and antibodies to hepatitis B surface
antigen (anti-HBs) using an enzyme immunoassay. Samples positive for anti-HBs
were tested for antibody to hepatitis B core antigen (anti-HBc) using a
chemiluminiscent microparticle immunoassay to distinguish between individuals
with past exposure to vaccine or natural infection. The estimated
age-standardized anti-HAV seroprevalence was 42.0% [95% confidence interval (CI) 
39.8-44.1] in the population >4 years of age. Seroprevalence was age-dependent
and highest in adult immigrants from Portugal and the former Yugoslavia. The
age-standardized prevalence of anti-HBs and anti-HBc was estimated at 19.7% (95% 
CI 18.1-21.3) and 3.16% (95% CI 2.2-4.1) respectively. Anti-HBs seroprevalence
exceeding 50% was found in the cohorts targeted by the routine hepatitis B
vaccination programme, which started in 1996. Our study illustrates that most
young people in Luxembourg are susceptible to HAV infection and that the
hepatitis B vaccination programme is having a substantial impact on population
immunity in children and teenagers.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16436219 [PubMed - indexed for MEDLINE]

256: J Viral Hepat. 2006 Feb;13(2):81-6.

Response to hepatitis A vaccine in HIV-positive patients.

Weissman S, Feucht C, Moore BA.

Infectious Disease Section, Department of Medicine, Hospital of Saint Raphael,
New Haven, CT, USA. sbw@alum.mit.edu

The USPHS/IDSA guidelines for Prevention of Opportunistic Infections in Persons
with human immunodeficiency virus (HIV) recommends that all susceptible HIV+
patients at increased risk for hepatitis A virus (HAV) or with chronic liver
disease, be vaccinated against HAV. Immune response to HAV vaccine has not been
well studied in HIV+ patients. In particular, there is little information in the 
literature regarding the effect and relationship of the CD4 count and the immune 
response in HIV patients. A retrospective analysis of HIV+ patients who received 
HAV vaccine was performed, and the antibody response to HAV (anti-HAV) measured. 
Univariate and multivariate analyses were performed to determine predictors of
response to vaccine administration. Of the 503 patients evaluated, 138 patients
completed their HAV vaccination series and 48% of them had postvaccine anti-HAV
positive results (responders). There was no difference in age, race,
antiretroviral therapy use, or hepatitis C virus exposure between responders and 
nonresponders. In univariate analysis, responders were more likely to be female
(40.3%vs 21.1%, P = 0.01), have a higher CD4 count at vaccine (508.6 cells/mm3 vs
344.3 cells/mm3, P = 0.001) and marginally lower viral load at vaccine (2.65 log 
copies vs 2.94 log copies, P = 0.07). Multivariate analysis showed that female
gender and higher CD4 count at vaccine were independent predictors of response to
vaccine. Forty-eight per cent of our HIV+ patients responded to HAV vaccine
administration. This is much lower than reported rates of 100% in HIV-negative
patients. Female gender and CD4 count at vaccine, but not CD4 nadir, predicted
response to vaccine.

PMID: 16436125 [PubMed - indexed for MEDLINE]

257: Clin Infect Dis. 2006 Feb 15;42(4):490-7. Epub 2006 Jan 11.

Hepatitis A virus infections in travelers, 1988-2004.

Mutsch M, Spicher VM, Gut C, Steffen R.

Division of Epidemiology and Prevention of Communicable Diseases, World Health
Organization Collaborating Centre for Travelers' Health, Institute of Social and 
Preventive Medicine, University of Zurich, Zurich, Switzerland.
muetsch@ifspm.unizh.ch

BACKGROUND: Uncertainty exists about the current risk of hepatitis A virus
infection in nonimmune travelers to destinations with high or intermediate risk
of transmission. We analyzed recent epidemiological data on imported hepatitis A 
to determine region-specific attack rates and incidences. METHODS: Surveillance
data on hepatitis A virus infections diagnosed during 1988-2004 were evaluated on
the basis of notification by laboratories, additional reports of physicians, and 
traveler's statistics. This study focuses on international travelers with
hepatitis A virus infection detected after their return to Switzerland. RESULTS: 
The rate of imported hepatitis A virus infections decreased 75% from 1988 to 2004
and accounted overall for 42% of all hepatitis A cases reported in Switzerland.
The actual incidence of hepatitis A in travelers to countries of high or
intermediate risk of transmission was 3.0-11.0 per 100,000 person-months abroad
for all travelers and 6.0-28.0 per 100,000 for those presumed to be nonimmune.
The actual proportion of those visiting friends and relatives among patients with
hepatitis A has increased to 28.2%, with children aged 0-14 years predominating. 
Reductions in the incidence by hepatitis A vaccination were estimated to vary
between 35.0% and 61.8% for different destinations. CONCLUSIONS: The risk of
hepatitis A virus infections has decreased by a factor of 10-50-fold over time,
compared with findings from older studies. The risk, however, remains very
considerable at many destinations, including frequently visited places, such as
Mexico. Children of immigrants are a high-risk population. Strategies are needed 
to reach those at highest risk.

Publication Types: 
    Comparative Study

PMID: 16421793 [PubMed - indexed for MEDLINE]

258: Clin Microbiol Rev. 2006 Jan;19(1):63-79.

Diagnosis of hepatitis a virus infection: a molecular approach.

Nainan OV, Xia G, Vaughan G, Margolis HS.

Centers for Disease Control and Prevention, 1600 Clifton Road, N.E., Mailstop
A33, Atlanta, GA 30333, USA. ovn1@cdc.gov

Current serologic tests provide the foundation for diagnosis of hepatitis A and
hepatitis A virus (HAV) infection. Recent advances in methods to identify and
characterize nucleic acid markers of viral infections have provided the
foundation for the field of molecular epidemiology and increased our knowledge of
the molecular biology and epidemiology of HAV. Although HAV is primarily shed in 
feces, there is a strong viremic phase during infection which has allowed easy
access to virus isolates and the use of molecular markers to determine their
genetic relatedness. Molecular epidemiologic studies have provided new
information on the types and extent of HAV infection and transmission in the
United States. In addition, these new diagnostic methods have provided tools for 
the rapid detection of food-borne HAV transmission and identification of the
potential source of the food contamination.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 16418523 [PubMed - indexed for MEDLINE]

259: Epidemiol Infect. 2006 Feb;134(1):87-93.

Detection of hepatitis A virus from clotting factors implicated as a source of
HAV infection among haemophilia patients in Korea.

Jee YM, Go U, Cheon D, Kang Y, Yoon JD, Lee SW, Shin YH, Kim KS, Lee JK, Jeong
EK, Yang BK, Cho HW.

Division of Enteric and Hepatitis Viruses, Department of Virology, National
Institute of Health, Seoul, Korea. ymeejee@nih.go.kr

To investigate the causal relationship of blood clotting factors and hepatitis A 
virus (HAV) infection in haemophilia patients during 1998-1999 in Korea, we
performed a 1:3 matched case-control study and molecular detection of HAV from
clotting factors and patients. The epidemiological investigation showed that one 
lot of clotting factor VIII was related epidemiologically to patients with
hepatitis A with an odds ratio of 35.0, or 38.4 when adjusted for the interval
between injections. We examined 17 sera collected from seven patients and 124
lots of blood clotting factors (factor VIII and factor IV) by HAV reverse
transcriptase-polymerase chain reaction (RT-PCR). HAV RNA was detected in five
clotting factors and six sera. The HAV sequence of one of the factor VIII samples
was identical to the sequences found in three patients' sera. Findings from the
laboratory and epidemiological studies suggested that the clotting factor was
causally related to HAV infection in three haemophilia patients.

PMID: 16409654 [PubMed - indexed for MEDLINE]

260: Biostatistics. 2006 Jul;7(3):422-37. Epub 2006 Jan 11.

A two-component model for counts of infectious diseases.

Held L, Hofmann M, Höhle M, Schmid V.

Department of Statistics, Ludwig-Maximilians-Universität München, Ludwigstrasse
33, 80539 München, Germany. leonhard.held@stat.uni-muenchen.de

We propose a stochastic model for the analysis of time series of disease counts
as collected in typical surveillance systems on notifiable infectious diseases.
The model is based on a Poisson or negative binomial observation model with two
components: a parameter-driven component relates the disease incidence to latent 
parameters describing endemic seasonal patterns, which are typical for infectious
disease surveillance data. An observation-driven or epidemic component is modeled
with an autoregression on the number of cases at the previous time points. The
autoregressive parameter is allowed to change over time according to a Bayesian
changepoint model with unknown number of changepoints. Parameter estimates are
obtained through the Bayesian model averaging using Markov chain Monte Carlo
techniques. We illustrate our approach through analysis of simulated data and
real notification data obtained from the German infectious disease surveillance
system, administered by the Robert Koch Institute in Berlin. Software to fit the 
proposed model can be obtained from http://www.statistik.lmu.de/ approximately
mhofmann/twins.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16407470 [PubMed - indexed for MEDLINE]

261: Pediatrics. 2006 Jan;117(1):30-3.

Factors associated with hepatitis a vaccination among children 24 to 35 months of
age: United States, 2003.

Amon JJ, Darling N, Fiore AE, Bell BP, Barker LE.

Epidemic Intelligence Service, Epidemiology Program Office, Centers for Disease
Control and Prevention, Atlanta, GA 30333, USA.

OBJECTIVES: In 1999, the Advisory Committee on Immunization Practices made
recommendations for hepatitis A vaccination of children according to historic
rates of hepatitis A incidence in different regions of the country. The objective
of this study was to examine hepatitis A vaccination coverage rates among
children living in states with different vaccination recommendations and to
examine individual characteristics associated with vaccination. METHODS:
Hepatitis A vaccination status data were collected for children 24 to 35 months
of age through the National Immunization Survey, a telephone survey with health
care provider-verified vaccination results. Vaccination status data were
collected from children in each of the 50 states and 28 selected urban areas.
RESULTS: In 2003, 50.9% (95% confidence interval [CI]: 47.6-54.2%) of children
living in 11 states where routine hepatitis A vaccination is recommended had
received > or =1 dose, compared with 25.0% (95% CI: 21.8-28.2%) of children in 6 
states where vaccination is suggested and 1.4% (95% CI: 1.0-1.8%) of children in 
33 states without a recommendation. Coverage was higher among children who lived 
in urban areas, were Hispanic or American Indian/Alaska Native, or were born to
women with less education. CONCLUSIONS: Hepatitis A vaccination is being targeted
successfully to children at higher risk of infection; however, overall
vaccination coverage remains lower for hepatitis A vaccination, compared with
other routine childhood vaccinations.

PMID: 16396857 [PubMed - indexed for MEDLINE]

262: Epidemiol Infect. 2006 Aug;134(4):863-71. Epub 2005 Dec 22.

An evaluation and comparison of three commonly used statistical models for
automatic detection of outbreaks in epidemiological data of communicable
diseases.

Rolfhamre P, Ekdahl K.

Department of Epidemiology, Swedish Institute for Infectious Disease Control
(SMI), Solna, Sweden. per.rolfhamre@smi.ki.se

We evaluated three established statistical models for automated 'early warnings' 
of disease outbreaks; counted data Poisson CuSums (used in New Zealand), the
England and Wales model (used in England and Wales) and SPOTv2 (used in
Australia). In the evaluation we used national Swedish notification data from
1992 to 2003 on campylobacteriosis, hepatitis A and tularemia. The average
sensitivity and positive predictive value for CuSums were 71 and 53%, for the
England and Wales model 87 and 82% and for SPOTv2 95 and 49% respectively. The
England and Wales model and the SPOTv2 model were superior to CuSums in our
setting. Although, it was more difficult to rank the former two, we recommend the
SPOTv2 model over the England and Wales model, mainly because of a better
sensitivity. However, the impact of previous outbreaks on baseline levels was
less in the England and Wales model. The CuSums model did not adjust for previous
outbreaks.

Publication Types: 
    Evaluation Studies

PMID: 16371181 [PubMed - indexed for MEDLINE]

263: J Viral Hepat. 2006 Jan;13(1):67-71.

Exposure to HAV infection in patients with chronic liver disease in Italy, a
multicentre study.

Sagnelli E, Stroffolini T, Almasio P, Mele A, Coppola N, Ferrigno L, Scolastico
C, Onofrio M, Imparato M, Filippini P.

Section of Infectious Diseases, Department of Medicine and Public Health, Second 
University of Naples, Naples, Italy. evangelista.sagnelli@unina2.it

We carried out a multicentre study on 2830 patients with chronic liver disease
from 79 liver units (25 in northern, 24 in central and 30 in southern Italy) to
evaluate naturally acquired immunity against hepatitis A virus (HAV) in relation 
to age, sex, geographical area of origin and entity of liver disease, and to
define the strategy for specific vaccination. Antibody to HAV (anti-HAV) was
detected in 1514 (53.5%) of the 2830 patients tested; the prevalence was 50.4% in
males and 59.1% in females. Both in central and southern Italy the prevalence of 
anti-HAV positive subjects increased with increasing age from 43.3 and 44.7%,
respectively, in the 0-30-year-old subjects to 80.1 and 68.3%, respectively, in
those aged over 60 years. The overall prevalence was much lower in northern
Italy, as were the variations from one age group to another, from 28.4% in the
0-30-year-old subjects to 38% in those aged over 60 years. 40.6% of patients with
cirrhosis lacked naturally acquired protection against HAV; this percentage was
higher in northern (60.5%) than in central (34.9%, P < 0.0001) and southern Italy
(27.6%, P < 0.0001). The high prevalence of patients in Italy with chronic
hepatitis or cirrhosis who lack naturally acquired immunity to HAV warrants the
implementation of vaccination programmes against hepatitis A in such patients.

Publication Types: 
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 16364085 [PubMed - indexed for MEDLINE]

264: J Gen Virol. 2006 Jan;87(Pt 1):115-8.

Analysis of sequential hepatitis A virus strains reveals coexistence of distinct 
viral subpopulations.

Costa-Mattioli M, Domingo E, Cristina J.

Department of Biochemistry and McGill Cancer Center, McGill University, Montreal,
Quebec, Canada.

Hepatitis A virus (HAV) is a hepatotropic member of the family Picornaviridae.
Despite a remarkable antigenic stability, recent results have shown that HAV
exists in vivo and in cell culture as distributions of genetically related,
non-identical variants, referred to as quasispecies. To gain insight into HAV
evolution over time in a specific geographical region, genotype I consensus
sequences from strains isolated in France in consecutive years were studied.
Phylogenetic neighbour-joining method and a non-hierarchical partition analysis, 
designed to analyse viral quasispecies, indicate that at least five distinct
subpopulations of HAV were identified in the course of the disease episode.
Strikingly, over time, different subpopulations cycled in dominance. The
coexistence of distinct subpopulations whose frequency varies with time is
consistent with quasispecies dynamics, and suggests that variation in the
dominant HAV population may provide HAV adaptability without being reflected in
significant antigenic variation.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16361423 [PubMed - indexed for MEDLINE]

265: Pancreatology. 2006;6(1-2):141-4. Epub 2005 Dec 13.

Comment in:
    Pancreatology. 2007;7(5-6):544-5.

Gallbladder sludge and acute pancreatitis induced by acute hepatitis A.

Basaranoglu M, Balci NC, Klör HU.

Department of Internal Medicine, Kadir Has University Hospital, Istanbul, Turkey.
basaranoglu@hotmail.com

In this case report, a young woman with gallbladder sludge and acute pancreatitis
due to acute hepatitis A (HAV) is presented. She was admitted to our hospital
with abnormal hepatic enzymes. Five days prior to her admission, an initial
abdominal ultrasound was performed at another hospital and revealed no
abnormality, while her serum aspartate aminotransferase (AST) level was at the
upper limit of normal (ULN) x 8. A second ultrasound was performed at our
hospital and revealed a gallbladder wall thickness (9.3 mm), gallbladder sludge
in the gallbladder lumen, pancreatic edema, ascites, and hepatomegaly while AST
was at the ULN x 50. Magnetic resonance imaging and magnetic resonance
cholangiopancreatography revealed imaging features of an acute stage of
pancreatitis and gallbladder wall thickness with coexisting sludge in the
gallbladder lumen. HAV infection was diagnosed by the detection of immunoglobulin
M against HAV in the serum. The patient underwent two repeated abdominal
ultrasound examinations on the 5th (AST was at the ULN x 3) and the 20th days
(AST was at the normal) after her discharge, and both revealed normal findings.
In our case, we observed reversible changes in the hepatobiliary and pancreatic
system which was related to the severity of hepatic necro-inflammation.
HAV-associated pancreatitis may be due to the formation of biliary sludge during 
the acute phase of the viral illness, but this association needs further
investigation. 2006 S. Karger AG, Basel and IAP

Publication Types: 
    Case Reports

PMID: 16354962 [PubMed - indexed for MEDLINE]

266: J Travel Med. 2005 Nov-Dec;12(6):319-26.

Combined typhoid fever and hepatitis A vaccine: comparison of immunogenicity and 
safety to concomitant monovalent vaccine over 3 years.

Overbosch D, Peyron F, Picot N, Varichon JP, Dumas R, Chambonneau L, Weber F.

Travel Clinic, Havenziekenhuis, Rotterdam, The Netherlands.

BACKGROUND: The safety and immunogenicity of Viatim, a combined hepatitis A (HA) 
and typhoid fever (Vi) vaccine, were compared with the monovalent component
vaccines up to and 1 month after a booster dose at 3 years. METHODS: Healthy,
adult volunteers were randomized to receive Viatim (group A, n = 179) or separate
HA and Vi vaccines (group B, n = 181); subgroups were boosted after 3 years with 
Viatim (groups C and D, n = 56 and 46, respectively). Local and systemic
reactions were recorded for 28 days postvaccination. Seroconversion and
seroprotection rates and geometric mean antibody concentrations were measured at 
14 and 28 days, 1, 2, and 3 years postvaccination, and 28 days after the booster 
dose. RESULTS: Local and systemic safety profiles were equivalent between the two
groups. Immediate local reactions were infrequent (1 in group A and 2 in group
B). Local reactions, consisting mostly of mild or moderate pain, were least
frequent with monovalent HA. Antibody concentrations to both antigens were
similar in groups A and B, in which HA seroprotection rates (> or = 20 mIU/mL)
were respectively, 98.7% and 100% at day 28, and 99.1% and 99.0% after 3 years,
achieving 100% after the booster. Vi seroprotection rates (> or = 1 microg/mL) of
85.2% and 84.9% after 28 days fell to 32.1% and 35.6% after 3 years, increasing
to 67.3% and 69.8% after the booster dose. CONCLUSIONS: The combined HA/Vi
vaccine, Viatim, had equivalent tolerability and safety and was as rapidly
immunogenic as its component monovalent vaccines when given concurrently. A
booster dose after 3 years significantly increased antibody levels with some
evidence of relative hyporesponsiveness of the typhoid response.

Publication Types: 
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 16343383 [PubMed - indexed for MEDLINE]

267: Sex Health. 2004;1(4):227-37.

Hepatitis A and B infection and vaccination in a cohort of homosexual men in
Sydney.

Jin F, Prestage GP, Pell CM, Donovan B, Van de Ven PG, Kippax SC, Kaldor JM,
Grulich AE.

National Centre in HIV Epidemiology and Clinical Research, the University of New 
South Wales, Sydney, NSW 2010, Australia. jjin@nchecr.unsw.edu.au

OBJECTIVES: To determine the prevalence and incidence of hepatitis A (HAV) and B 
(HBV) infection and vaccination in HIV-negative homosexual men in Sydney, and
associated risk factors. METHODS: An open prospective cohort study was conducted 
among a community-based sample of HIV-negative homosexual men in Sydney in
2001-02. Participants underwent a face-to-face interview, regarding demographics,
sexual behavioural risk factors and sexually transmitted infections, and blood
samples were collected. They were followed annually. RESULTS: Nine hundred and
three men completed a baseline interview by the end of 2002. Among them, 68% were
seropositive to hepatitis A. The seroprevalence of prior hepatitis B infection
was 19%, and 53% had serological evidence of HBV vaccination. Younger men were
much more likely to be seronegative, with 48% and 46% of <25-year-olds being
seronegative to HAV and HBV respectively. In multivariate analysis HAV and HBV
infection were associated with increasing age, greater number of lifetime sex
partners and HBV infection was also associated with previous sexually transmitted
infections. HAV vaccination was associated with increasing age, greater number of
lifetime sex partners, overseas travel in the last year and self-reported
anogenital warts. HBV vaccination was associated with higher occupational status,
greater lifetime number of sex partners and previous sexually transmitted
infections. CONCLUSION: Substantial proportions of gay community-attached young
homosexual men are still at risk of HAV and HBV infection. This study points to a
need for vaccination strategies which ensure high levels of hepatitis A and B
immunity in young sexually active gay men.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 16342422 [PubMed - indexed for MEDLINE]

268: Am J Epidemiol. 2006 Feb 1;163(3):204-10. Epub 2005 Dec 7.

Person-to-person transmission of hepatitis A virus in an urban area of
intermediate endemicity: implications for vaccination strategies.

Victor JC, Surdina TY, Suleimenova SZ, Favorov MO, Bell BP, Monto AS.

Department of Epidemiology, School of Public Health, University of Michigan, Ann 
Arbor, MI, USA.

Developing countries with an increasing hepatitis A disease burden may target
vaccination to specific groups, such as young children, as an initial control
strategy. To better understand transmission of hepatitis A virus in such
countries, the authors prospectively studied household and day-care/school
contacts of cases in Almaty, Kazakhstan. Overall, by the time of identification
of symptomatic index cases, half of transmission had already occurred, having
been detected retrospectively. The odds of household contacts' becoming infected 
were 35.4 times those for day-care/school contacts (95% confidence interval (CI):
17.5, 71.7). Within households, younger age of either index cases or susceptible 
contacts elevated the odds of secondary infection among susceptible contacts: The
presence of a case under 6 years of age raised the odds 4.7 times (95% CI: 1.2,
18.7); and compared with contacts aged 14 years or older, the odds of infection
were increased to 7.7 (95% CI: 1.5, 40.3) and 7.0 (95% CI: 1.4, 34.3) among
contacts aged 0-6 years and 7-13 years, respectively. Young children are
appropriate targets for sustainable hepatitis A vaccination programs in areas
undergoing hepatitis A epidemiologic transition. If vaccine is determined to be
highly effective postexposure and if it is feasible, vaccinating household
contacts could be a useful additional control strategy.

Publication Types: 
    Research Support, U.S. Gov't, P.H.S.

PMID: 16339053 [PubMed - indexed for MEDLINE]

269: Epidemiol Infect. 2006 Aug;134(4):799-802. Epub 2005 Dec 1.

An outbreak of hepatitis A in Southern Italy: the case for vaccinating food
handlers.

Prato R, Lopalco PL, Chironna M, Germinario C, Quarto M.

University of Foggia, Italy.

We report an outbreak of hepatitis A that occurred in the city of Bari (Apulian
region) in June 2002. Overall, 26 cases were observed over a 4-week period. These
were traced back to the index case, a food handler who prepared various food
products for sale over the counter at a store in the district (OR 5.36, CI 95%
1.58-19.25). Laboratory investigations confirmed that the outbreak was due to a
point source and identified a new genotype IB variant. There is a possible
indication for administration of hepatitis A vaccine to food handlers, although
further evidence of an acceptable cost-benefit ratio needs to be ascertained.

PMID: 16318653 [PubMed - indexed for MEDLINE]

270: Epidemiol Infect. 2006 Aug;134(4):803-7. Epub 2005 Nov 29.

Exposure to school children as a risk factor in a community outbreak of hepatitis
A in young adults: a case control study.

Roberts RJ, Palmer SR.

National Public Health Service, Preswylfa, Mold, Flintshire, UK.
richard.roberts@nphs.wales.nhs.uk

To investigate risk factors during a community outbreak of hepatitis A we carried
out a case- control study of 35 cases and 49 matched controls using an
interviewer-administered questionnaire on clinical history, travel, household
details including domestic toilet facilities, infectious contacts, and food
history. Of 99 cases notified in the city during the outbreak year, 50 (51%) were
young adults age 15-34 years. Hepatitis A infection was independently associated 
with household contact with a case (P=0.0005), and sharing a household with
children in primary school (OR 3.4, 95% CI 1.2-9.5, P=0.008) with risk increasing
with number of primary-school pupils in the household (chi(2) for linear trend
6.47, P=0.01). We concluded that in a population with a low prevalence of
hepatitis A, adults who live in the same household as primary-school-age children
are at increased risk of acquiring the infection during community outbreaks.

PMID: 16316491 [PubMed - indexed for MEDLINE]

271: Chin Med J (Engl). 2005 Nov 20;118(22):1851-6.

Persistent efficacy of live attenuated hepatitis A vaccine (H2-strain) after a
mass vaccination program.

Zhuang FC, Qian W, Mao ZA, Gong YP, Jiang Q, Jiang LM, Chen NL, Chai SA, Mao JS.

Institute of Viral Diseases, Zhejiang Academy of Medical Sciences, Hangzhou
310013, China. fczhuang@163.com

BACKGROUND: Live attenuated hepatitis A vaccine (H2 strain) is widely applied in 
prevention of hepatitis A epidemic in China and other countries now. It is
essential to observe and confirm the vaccine immune efficacy, population antibody
level and its persistent efficacy after mass immunization. METHODS: A total of
220 children with negative anti-HAV antibody (aged 1 - 3 years) were taken for
follow-up assay to observe seroconversion and geometric mean titre (GMT) level 2 
months, 12 months, 6 years, and 10 years after inoculation. Another survey
sampled from subjects of different age groups (3, 6, 9, 15, 18, 25 and 35 years) 
to compare anti-HA antibody positive rate before and after inoculation performed 
10 years previously. Epidemiological observations were taken for 10 years to
evaluate the relationship between vaccine coverage and hepatitis A morbidity.
Serum antibody to HAV was detected by enzyme linked immunoassay (ELISA,
calibrated by WHO international reference) and ABBOTT Axsym HAVAB microparticle
enzyme immunoassay. RESULTS: Seroconversion in follow-up assay 2 months and 10
years after inoculation was 98.6% and 80.2% respectively. For children, the
vaccination anti-HA antibody positive rates were significantly different before
and after 10 years, 7.69% cf 70.45% (aged 3 years) and 52.58% cf 71.78% (aged 18 
years). When vaccine coverage rose from 57% to 74%, there were no any HA
epidemics. When vaccine coverage reached 85%, there were no any HA cases. With
vaccine coverage between 85% and 91%, there were no any HA cases in cohorts from 
the age of 1 year to 15 years during the 10 years. CONCLUSIONS: Live attenuated
hepatitis A vaccine has an obvious long-term effectiveness in prevention and
control of HA epidemics through mass vaccination.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16313838 [PubMed - indexed for MEDLINE]

272: Vaccine. 2006 Mar 24;24(14):2685-91. Epub 2005 Nov 9.

Adverse events after hepatitis A B combination vaccine.

Woo EJ, Miller NB, Ball R; VAERS Working Group.

Food and Drug Administration, Center for Biologics Evaluation and Research, 1401 
Rockville Pike, Rockville, MD 20852, USA. wooj@cber.fda.gov

In May 2001, the U.S. Food and Drug Administration (FDA) approved Hepatitis A
Inactivated and Hepatitis B Recombinant Vaccine (HEPAB) for immunization of
adults. From May 2001 to September 2003, the Vaccine Adverse Event Reporting
System (VAERS) received 305 reports of adverse events after HEPAB. Many events
were similar to those reported after the monovalent hepatitis A and B vaccines.
Non-serious events included constitutional symptoms and local reactions. Serious 
events included neurologic, hepatobiliary, and dermatologic conditions, and
detailed medical and epidemiological review did not suggest a clear pattern of
evidence supporting a causal relationship with the vaccine, except for injection 
site reactions and some allergic reactions.

Publication Types: 
    Review

PMID: 16310295 [PubMed - indexed for MEDLINE]

273: Vaccine. 2005 Dec 30;23(50):5798-806.

Hepatitis A virus infection in the United States: serologic results from the
Third National Health and Nutrition Examination Survey.

Bell BP, Kruszon-Moran D, Shapiro CN, Lambert SB, McQuillan GM, Margolis HS.

Division of Viral Hepatitis, National Center for Infectious Diseases, MS G-37,
Centers for Disease Control and Prevention, 1600 Clifton Road NE, Atlanta, GA
30333, USA.

To determine the prevalence of hepatitis A virus (HAV) infection in the general
U.S. population, sera from participants in the Third National Health and
Nutrition Examination Survey (NHANES III) conducted in 1988-1994 were tested for 
antibody to HAV (anti-HAV). Among 21,260 participants aged > or = 6 years tested,
the overall prevalence of infection was 31.3%, and increased markedly with age.
The age-adjusted prevalence was significantly higher among foreign- compared to
U.S.-born participants, and was highest among Mexican-Americans and lowest among 
non-Hispanic whites. Among U.S.-born children, only Mexican-American ethnicity
and income below the poverty level were associated with HAV infection in a
multivariate model. During this period before hepatitis A vaccination, age,
ethnicity and birthplace were the most important determinants of HAV infection in
the United States.

PMID: 16307834 [PubMed - indexed for MEDLINE]

274: J Med Virol. 2006 Jan;78(1):18-23.

Seroepidemiology of hepatitis A, B, C, and E viruses infection among preschool
children in Taiwan.

Lin JB, Lin DB, Chen SC, Chen PS, Chen WK.

Graduate Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.

Taiwan was a hyperendemic area for hepatitis A and B viruses (HAV and HBV)
infection before late 1980s. To study the seroprevalence of hepatitis A, B, C,
and E viruses (HCV and HEV) infection among preschool children in Taiwan, a
community-based survey was carried out in 54 kindergartens in 10 urban areas, 10 
rural areas, and 2 aboriginal areas randomly selected through stratified
sampling. Serum specimens of 2,538 preschool children were screened for the
hepatitis A, C, and E antibodies by a commercially available enzyme immunoassay
and for HBV markers by radioimmunoassay methods. The multivariate-adjusted odd
ratios (OR) with their 95% confidence intervals (CI) were estimated through the
multiple logistic regression analysis. Females had a statistically significantly 
higher HAV seroprevalence than males. The seroprevalence of HCV infection
increased significantly with age. The larger the sibship size, the higher the
seroprevalence of HBV infection. Aboriginal children had a significantly higher
seroprevalence of HBV and HEV infection and lower seroprevalence of HCV infection
than non-aboriginal children. A significantly higher seroprevalence of HBV
infection was found in rural children than urban children. There was no
significant association between serostatus of HAV and HEV infection and between
serostatus of HBV and HCV infection among preschool children in Taiwan. The poor 
environmental and hygienic conditions in the aboriginal areas might play a role
in infection with HBV and HEV.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 16299720 [PubMed - indexed for MEDLINE]

275: Pediatr Infect Dis J. 2005 Nov;24(11):974-8.

Evaluation of a hepatitis A immunization program.

Duggirala HJ, Hassig SE, Santana S, Rice J.

Tulane University, New Orleans, LA, USA. hcj@cdrh.fda.gov

BACKGROUND: The purpose of this study was to evaluate the effectiveness of a
hepatitis A vaccine requirement targeted at child-care center attendees 2-5 years
of age in Maricopa County, AZ. A case-control study conducted before
implementation in 1997 found that individuals with hepatitis A were 6 times more 
likely to have worked in or attended a child-care center than were matched
controls, and 40% of hepatitis A cases were attributable to attending or working 
in a child-care center. METHODS: A case-control study was conducted
postimplementation in 1999. Cases were individuals reported to surveillance staff
between August 1, 1999 and April 30, 2000. Cases were included if they met the
Centers for Disease Control and Prevention hepatitis A surveillance case
definition. Each case (n = 72) was matched to 2 controls (n = 144) based on age
and neighborhood. RESULTS: Cases were more likely to have had contact with a
hepatitis A case [odds ratio (OR), 7.04; 95% confidence interval (CI), 1.96,
25.31] than were their matched controls in the unadjusted analysis. Individuals
with direct contact with a child-care center (OR 0.221; CI 0.05, 0.99) were
protected against disease. In the multivariate analysis, contact with a hepatitis
A case (OR 5.63; CI 1.22, 25.91) was significantly associated with disease, and
the protective effect of education (OR 0.19; CI 0.06, 0.60) remained significant.
CONCLUSION: The results of this study suggest the vaccination requirement had
some impact on the epidemiology of hepatitis A in Maricopa County. The risk
associated with child-care centers seen in the 1997 study is no longer
significantly associated with hepatitis A disease.

Publication Types: 
    Evaluation Studies

PMID: 16282932 [PubMed - indexed for MEDLINE]

276: World J Gastroenterol. 2005 Oct 14;11(38):6069-71.

Autoimmune hepatitis triggered by acute hepatitis A.

Tanaka H, Tujioka H, Ueda H, Hamagami H, Kida Y, Ichinose M.

3(rd) Department of Internal Medicine, Wakayama Medical University, 811-1
Kimiidera, Wakayama 641-0015, Japan. h-tana@yf6.so-net.ne.jp

The patient was a 57-year-old woman presenting with jaundice as the chief
complaint. She began vomiting on July 10, 2003. Jaundice was noted and admitted
to our hospital for thorough testing. Tests on admission indicated severe
hepatitis, based on: aspartate aminotransferase (AST), 1 076 IU/L; alanine
aminotransferase (ALT), 1 400 IU/L; total bilirubin (TB), 20.9 mg/dL; and
prothrombin time rate (PT%), 46.9%. Acute hepatitis A (HA) was diagnosed based on
negative hepatitis B surface antigen and hepatitis C virus RNA and positive
immunoglobulin (Ig) M HA antibody, but elevation of anti-nuclear antigen (X320)
and IgG (3 112 mg/dL) led to suspicion of autoimmune hepatitis (AIH). Plasma
exchange was performed for 3 d from July 17, and steroid pulse therapy was
performed for 3 d starting on July 18, followed by oral steroid therapy. Liver
biopsy was performed on August 5, and the results confirmed acute hepatitis and
mild chronic inflammation. Levels of AST and ALT normalized, so dose of oral
steroid was markedly reduced. Steroid therapy was terminated after 4 mo, as the
patient had glaucoma. Starting 3 mo after cessation of steroid therapy, levels of
AST and ALT began to increase again. Another liver biopsy was performed and AIH
was diagnosed based on serum data and biopsy specimen. Oral steroid therapy was
reinitiated. Levels of AST and ALT again normalized. The present case was thus
considered to represent AIH triggered by acute HA.

Publication Types: 
    Case Reports
    Review

PMID: 16273628 [PubMed - indexed for MEDLINE]

277: Am J Med. 2005 Oct;118 Suppl 10A:100S-108S.

Public health perspective on vaccine-preventable hepatitis: integrating hepatitis
A and B vaccines into public health settings.

Hershey JH, Schowalter L, Bailey SB.

New River Health District, Virginia Department of Health, Christiansburg,
Virginia 24079, USA. jody.hershey@vdh.virginia.gov

Hepatitis A and B vaccinations can and should be integrated into public health
settings that serve adults at high risk for infection (e.g., sexually transmitted
disease and/or human immunodeficiency virus clinics, criminal justice settings), 
and a policy of universal immunization may be the best way to accomplish this
goal in these settings. Although hepatitis vaccines should be given to all
susceptible persons at risk, many opportunities to vaccinate adults at high risk 
are missed, and there are several barriers and challenges to vaccination of
adults. These challenges and barriers can be overcome. Successful integration of 
hepatitis vaccination for adults into existing public health services and clinics
has been accomplished across the United States at both state and local levels.
Additional funds must be provided for the infrastructure and purchase of vaccines
for adults in these settings.

Publication Types: 
    Review

PMID: 16271550 [PubMed - indexed for MEDLINE]

278: Am J Med. 2005 Oct;118 Suppl 10A:84S-89S.

A call to immunize the correctional population for hepatitis A and B.

Gondles EF.

Institute for Criminal Justice Healthcare, Arlington, Virginia 22207, USA.
desifl@aol.com

An increasing number of the 12 million people who pass through jails and prisons 
in the United States each year are infected with hepatitis B or C. Many have
routinely engaged in sexual and drug-use behaviors that put them and their
contacts at risk for infection, and many are likely to return to these behaviors 
on their release, further spreading the infection. Thus, the prevalence of
hepatitis infections among the incarcerated population is an enormous health
problem not only for the correctional system but also for the community at large.
There is no federal mandate for screening members of the incarcerated population 
who may be at risk or those who are already infected. Public health and
correctional authorities must join forces to offer educational programs,
prevention services, and intervention strategies to offenders, many of whom have 
their first contact with the healthcare system when they enter a correctional
facility. Safe and effective vaccines for hepatitis A and B have been available
for >11 years and, despite the challenges of conducting an immunization program
for this population, the correctional environment provides a unique opportunity
to reach these individuals and reduce the spread of viral hepatitis.

Publication Types: 
    Review

PMID: 16271547 [PubMed - indexed for MEDLINE]

279: Am J Med. 2005 Oct;118 Suppl 10A:75S-83S.

Hepatitis A and B immunizations of individuals infected with human
immunodeficiency virus.

Laurence JC.

Laboratory for AIDS Virus Research, Division of Hematology-Oncology, Weill
Medical College of Cornell University, New York, New York 10021, USA.
jlaurenc@med.cornell.edu

All persons at risk for infection with human immunodeficiency virus (HIV) types 1
and 2, including men who have sex with men, those with multiple heterosexual
contacts, abusers of illegal injection drugs, and persons frequently exposed to
blood and blood products, are also at high risk for hepatitis A virus (HAV) and
acute and chronic hepatitis B virus (HBV) infections. HIV can prolong the
duration and increase the level of HAV viremia and augment HAV-related liver
abnormalities. HIV also magnifies HBV viremia and the risk of HBV reactivation,
chronic active HBV infection, cirrhosis, and death. Because of these concerns,
hepatitis A vaccination is recommended for all HIV-positive/HAV seronegative
persons, with 2 standard doses given 6 to 12 months apart. Immune response to
hepatitis A vaccines is excellent, even in moderately immune-suppressed
individuals. Hepatitis B vaccination is also recommended for all HIV-positive
persons lacking prior immunity. However, immune reactivity to hepatitis B
vaccines is frequently suboptimal in terms of patients' rate of response,
antibody titer, and durability. Relatively high CD4+ T-cell counts (> or
=500/mm3) and low levels of HIV viremia (<1,000 RNA genome copies/mL plasma) are 
necessary to ensure adequate hepatitis B vaccine response. Higher hepatitis B
vaccine doses, prolongation of the vaccination schedule, or both, as prescribed
for many patients with non-HIV-related immune deficiencies, may be considered
initially. Revaccination should be instituted if postvaccination titers of
antibodies to hepatitis B surface antigen are <10 mIU/mL (<10 IU/L).
Nonresponders may also react to a subsequent vaccine course if CD4+ T-cell counts
rise to 500/mm3 following institution of highly active antiretroviral therapy;
vaccine adjuvant trials are under way. Universal, age-based immunization of all
young and middle-aged adults appears to be the most comprehensive way of
protecting all populations who are at high risk.

Publication Types: 
    Review

PMID: 16271546 [PubMed - indexed for MEDLINE]

280: Am J Med. 2005 Oct;118 Suppl 10A:69S-74S.

Hepatitis A and B immunization in persons being evaluated for sexually
transmitted diseases.

Handsfield HH.

Center for AIDS and STD, University of Washington, and the Department of
Medicine, Harborview Medical Center, Seattle, Washington 98106, USA.
hhh@u.washington.edu

Sexual transmission accounts for the majority of hepatitis B virus (HBV)
infections in industrialized countries. Hepatitis A virus (HAV) can be
transmitted by sexual practices that involve fecal-oral exposure. Both infections
are disproportionately frequent in men who have sex with men (MSM). Routine
immunization against HBV is recommended for MSM and for persons being evaluated
or treated for sexually transmitted diseases (STDs), and HAV immunization is
advised for MSM and for other persons at risk who are commonly seen in STD care
settings, such as users of illegal drugs. However, numerous attitudinal and
structural barriers interfere with routine immunization in persons at risk for
sexual acquisition of HAV and HBV. Substantial success has been documented in
vaccinating persons at risk in public STD clinics and other settings; however, at
a national level, efforts to achieve desired immunization rates have largely
failed. Until universal childhood immunization produces a largely immune adult
population, the universal vaccination of adults-as a supplement to the current
risk-based approaches-may be worthwhile to achieve immunization of persons at
risk for sexual transmission of HBV.

Publication Types: 
    Review

PMID: 16271545 [PubMed - indexed for MEDLINE]

281: Am J Med. 2005 Oct;118 Suppl 10A:58S-62S.

Hepatitis A vaccine in the last-minute traveler.

Connor BA.

Weill Medical College of Cornell University, and The New York Center for Travel
and Tropical Medicine, New York, New York 10021, USA. bconnor@pol.net

Current recommendations state that travelers should receive hepatitis A vaccine 2
to 4 weeks before departure. Such recommendations, however, may dissuade
last-minute travelers from receiving the vaccine. A preponderance of evidence
exists to support hepatitis A vaccination of the imminent-departure traveler and 
therefore suggests that these guidelines merit reconsideration. In examining this
issue, one of the most important elements to determine is the amount of time
required for seroconversion following vaccination. Clinical trials of hepatitis A
vaccines measured antibody response at 2 and 4 weeks after vaccination. However, 
studies investigating early seroconversion found that the vast majority of
vaccinees develop antibodies within 2 weeks of vaccination, some as early as 12
days after vaccination. This is relevant information, given that the hepatitis A 
virus has an average incubation period of 28 days. Seroconversion is predicated
on achieving a "protective" antibody level. However, levels of antibody
considered protective remain debatable. Evidence suggests that clinical disease
does not occur at antibody levels lower than those currently accepted as
protective. Furthermore, hepatitis A vaccine has been proved effective in
controlling outbreaks worldwide. Research data show that a single dose of vaccine
can halt outbreaks if an adequate number of susceptible individuals are
vaccinated. Information from rapid-outbreak control studies and those assessing
postexposure administration of hepatitis A vaccine suggest that late vaccination 
provides a significant degree of protection. For these reasons, hepatitis A
vaccine may be administered at any time before departure because it will still
provide travelers with protection.

Publication Types: 
    Review

PMID: 16271543 [PubMed - indexed for MEDLINE]

282: Am J Med. 2005 Oct;118 Suppl 10A:50S-57S.

Comment in:
    Am J Med. 2007 Aug;120(8):e17-8; author reply e19.

United States epidemiology of hepatitis A: influenced by immigrants visiting
friends and relatives in Mexico?

Jong EC.

Department of Medicine, University of Washington School of Medicine, Seattle,
Washington 98195, USA. ecjong@u.washington.edu

Among the industrialized nations, the United States annually receives the
greatest number of immigrants as permanent residents. Immigrants from Mexico have
represented the largest segment of the foreign-born population in recent decades,
and continued growth of Mexican immigration is predicted for the decades ahead.
The changing demographics of this population, including the emergence of new
immigrant growth centers, will influence the future epidemiology of hepatitis A
virus transmission in the United States. Travel home to the place of origin to
visit friends and relatives (VFR) by both newly arrived and established Mexican
immigrants constitutes a new group of travelers that now include
intergenerational family units. Asymptomatic pediatric travelers-who acquire
hepatitis A abroad and are infectious on return to American
communities-contribute to the silent transmission of hepatitis A to playmates,
caretakers, and contacts in households, daycare facilities, and elementary
schools. Considering the expanded geographic distribution of Mexican immigrant
settlement, the predicted increased diversity of pediatric populations in the
United States over time, and the continued growth of VFR travel, a universal
pediatric vaccine recommendation for hepatitis A immunization can help to prevent
hepatitis A transmission in this country in the future.

Publication Types: 
    Review

PMID: 16271542 [PubMed - indexed for MEDLINE]

283: Am J Med. 2005 Oct;118 Suppl 10A:46S-49S.

Changing travel-related global epidemiology of hepatitis A.

Steffen R.

Division of Communicable Diseases and Travel Clinic, Institute of Social and
Preventive Medicine of the University of Zurich, World Health Organization
Collaborating Center for Travelers' Health, Zurich, Switzerland.
travclin@ifspm.unizh.ch

Hepatitis A is highly endemic in many emerging cultures. Despite the availability
of safe and effective vaccines and some improvements in sanitation in developing 
countries, hepatitis A remains a significant cause of morbidity for nonimmune
travelers visiting such destinations. All are at risk, including short-term
vacationers or business travelers who stay in deluxe accommodations. This may
have considerable implications on public health. Hepatitis A vaccination programs
for travelers have not proven to be effective, since many visitors to
destinations at risk (e.g., Mexico) fail to consult health professionals prior to
departure. Because 50% of the US population has an anticipated lifetime risk for 
exposure, universal immunization against hepatitis A should be considered.

Publication Types: 
    Review

PMID: 16271541 [PubMed - indexed for MEDLINE]

284: Am J Med. 2005 Oct;118 Suppl 10A:21S-27S.

Acute hepatitis A and B in patients with chronic liver disease: prevention
through vaccination.

Keeffe EB.

Division of Gastroenterology and Hepatology, Department of Medicine, Stanford
University School of Medicine, Stanford, California, USA. ekeefe@stanford.edu

Retrospective and prospective studies have demonstrated that the occurrence of
acute hepatitis A in patients with chronic liver disease is associated with
higher rates of morbidity and mortality than in previously healthy individuals
with acute hepatitis A. The mortality associated with acute hepatitis A may be
particularly high in patients with preexisting chronic hepatitis C. Although
acute hepatitis B in patients with preexisting chronic liver disease is less well
studied, worse outcomes than in previously healthy individuals are apparent.
However, numerous studies convincingly demonstrate that chronic hepatitis B virus
coinfection with hepatitis C virus (or hepatitis D virus) is associated with an
accelerated natural history of liver disease and worse outcomes. These
observations led to studies that demonstrated the safety and efficacy of
hepatitis A and hepatitis B vaccination in patients with mild-to-moderate chronic
liver disease. Hepatitis A and B vaccination is less effective in patients with
advanced liver disease, especially after decompensation, such as in patients
awaiting liver transplantation, and in liver transplant recipients. The emerging 
lower rates of inherent immunity in younger individuals, higher morbidity and
mortality of acute hepatitis A or B superimposed on chronic liver disease, and
greater vaccine efficacy in milder forms of chronic liver disease suggest that it
is a reasonable policy to recommend hepatitis A and B vaccination in patients
early in the natural history of chronic liver disease.

Publication Types: 
    Review

PMID: 16271537 [PubMed - indexed for MEDLINE]

285: Am J Med. 2005 Oct;118 Suppl 10A:16S-20S.

Comment in:
    Am J Med. 2007 Aug;120(8):e17-8; author reply e19.

Evaluating existing recommendations for hepatitis A and B vaccination.

Poland GA.

Mayo Vaccine Research Group, Program in Translational Immunovirology and
Biodefense, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota
55905, USA. poland.gregory@mayo.edu

Hepatitis A and hepatitis B vaccines are now widely available throughout the
United States, Europe, and most of the rest of the world. A recombinant hepatitis
B vaccine was licensed in the United States in 1986, followed by hepatitis A
vaccine in 1995. Official recommendations from the Advisory Committee on
Immunization Practices were published for hepatitis B vaccine in 1990, with
revisions in 1991, and for hepatitis A vaccine in 1999. Unfortunately, the
recommendations are not closely followed, and an insufficient number of persons
who are at risk receive these vaccines. In addition, the available
recommendations may not cover all who are at risk for infection. This article
reviews existing recommendations for the use of hepatitis A and hepatitis B
vaccines and offers suggestions for situations in which additional
recommendations may be useful. The rationale for revising and expanding the
existing recommendations is based on questions raised about the value of
risk-based recommendations, data demonstrating increasing rates of hepatitis A
and B infections in specific age groups, and the failure to protect 50% of
individuals who become infected with vaccine-preventable hepatitis.

Publication Types: 
    Review

PMID: 16271536 [PubMed - indexed for MEDLINE]

286: Am J Med. 2005 Oct;118 Suppl 10A:7S-15S.

Experience with hepatitis A and B vaccines.

Davis JP.

Bureau of Communicable Diseases and Preparedness, Wisconsin Division of Public
Health, Madison, Wisconsin 53702, USA. davisjp@dhfs.state.wi.us

The lengthy history of efforts to understand the pathogenesis and means of
preventing and controlling both hepatitis A and B is noteworthy for many
exceptional scientific achievements. Among these are the development of vaccines 
to prevent the spread of infection through induction of active immunity to
hepatitis A virus (HAV) and hepatitis B virus (HBV). The first plasma-derived
hepatitis B vaccine was licensed in the United States in 1981 and was replaced by
recombinant hepatitis B vaccines in 1986 and 1989. Vaccines to prevent HAV
infection were licensed in the United States in 1995 and 1996. Subsequently,
combination vaccines that included both hepatitis A and B vaccine components, or 
the hepatitis B component in combination with other commonly administered
vaccines, were licensed in the United States. Despite significant reductions in
hepatitis-related morbidity and mortality that have resulted from widespread use 
of these vaccines, vaccine-preventable morbidity and mortality still occur. The
purposes of this article are to review clinical trial and other experience with
hepatitis A and B vaccines in healthy individuals as well as in those with
chronic liver disease, infected with the human immunodeficiency virus, or
requiring hemodialysis; describe the impact that these vaccines and national
recommendations for vaccination have had on reducing the incidence of HAV and HBV
infection; and recommend expansion of these recommendations to include universal 
vaccination of adults as a means of further reducing the burden of viral
hepatitis.

Publication Types: 
    Review

PMID: 16271535 [PubMed - indexed for MEDLINE]

287: Turk J Gastroenterol. 2005 Jun;16(2):102-4.

The coexistence of hepatitis A and infectious mononucleosis.

Karagöz G, Ak O, Ozer S.

Department of Infectious Diseases and Clinical Microbiology, Kartal Training and 
Research Hospital, 81327 Kartal, Istanbul, Turkey. gulkaragozmd@hotmail.com

Hepatitis A is an acute, self-limited disease that spreads predominantly by the
fecal-oral route. Hepatitis A characteristically has an acute, sudden
influenza-like onset with a prominence of myalgia, headache, fever and malaise.
Infectious mononucleosis is an acute illness characterized clinically by sore
throat, fever and lymphadenopathy. The virus usually spreads from person to
person by close contact with nasopharyngeal secretions. In this case the
coexistence of both diseases in the same patient is found interesting.

Publication Types: 
    Case Reports

PMID: 16252202 [PubMed - indexed for MEDLINE]

288: Clin Infect Dis. 2005 Nov 15;41(10):1537-40. Epub 2005 Oct 13.

Reduced-dose intradermal vaccination against hepatitis A with an aluminum-free
vaccine is immunogenic and can lower costs.

Pancharoen C, Mekmullica J, Thisyakorn U, Kasempimolporn S, Wilde H, Herzog C.

Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok,
Thailand. Chitsanu.P@Chula.ac.th

A reduced dose (0.1 mL) of intradermal hepatitis A virus (HAV) vaccine could
facilitate the control of hepatitis A in countries of endemicity. All study
subjects receiving an aluminum-free HAV vaccine intradermally were seroprotected 
28 days after vaccination (anti-HAV titer, > or =10 mIU/mL). Seroprotection rates
decreased to 80.8% at 12 months but returned to 100%, with titers increasing
28-fold, after receipt of a booster vaccination.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16231271 [PubMed - indexed for MEDLINE]

289: J Travel Med. 2005 Apr;12 Suppl 1:S12-21.

Overlapping epidemiologies of hepatitis A and typhoid fever: the needs of the
traveler.

Luxemburger C, Dutta AK.

Medical Affairs Sanofi Pasteur, Lyon, France.

Hepatitis A and typhoid fever are endemic infectious diseases in many parts of
the world. They share a common, simple mode of transmission--the fecal--oral
route-associated with poor hygiene. The low endemicity of both diseases in
developed countries, and the rise in travel to exotic destinations for business
and leisure, mean that increasing numbers of travelers are being exposed to
infection. Effective, established vaccines are available against both diseases,
and recently new formulations combining both vaccines in one injection have been 
licensed. We review the present epidemiologic situation for both diseases, to
determine the necessity to routinely vaccinate travelers against both diseases.

Publication Types: 
    Review

PMID: 16225802 [PubMed - indexed for MEDLINE]

290: Clin Pediatr (Phila). 2005 Oct;44(8):705-9.

Hepatitis A immunization strategies: universal versus targeted approaches.

Jacobs RJ, Meyerhoff AS, Zink T.

Capitol Outcomes Research, Inc., Alexandria, VA 22310, USA.

The alternative to nationwide childhood hepatitis A vaccination is to continue
targeting high-risk adults. To consider how many of today's children will become 
vaccination candidates, the proportion of adults reporting a lifetime history of 
hepatitis A risk factors was examined. One thousand thirty-four US adults
responded to a confidential postal survey, 49% of whom had met current Advisory
Committee on Immunization Practices (ACIP) criteria for immunization and 72% had 
met an expanded set of criteria. Because adult vaccination is more costly per
capita, targeted vaccination may provide modest financial savings with none of
the benefits associated with reduced child-to-adult transmission.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16211195 [PubMed - indexed for MEDLINE]

291: Epidemiol Infect. 2006 Jun;134(3):498-505. Epub 2005 Oct 5.

Clusters of autochthonous hepatitis A cases in a low endemicity area.

Guis H, Clerc S, Hoen B, Viel JF.

Department of Public Health, Biostatistics and Epidemiology Unit, Faculty of
Medicine, Besançon, France.

At the University Hospital of Besançon (département of Doubs, France), an
unusually high number of patients were hospitalized for hepatitis A during the
1999-2000 period, some of whom had not travelled abroad. This prompted us to
conduct an investigation on a population basis and search for clusters of cases
possibly related to local sources of contamination. Accordingly, case definition 
was restricted to autochthonous cases. During the 1999-2002 period, 45
autochthonous cases were classified as possibly originating from local
environmental sources. A space-time scan statistic detected one most likely
cluster (standardized incidence ratio 20.63, 95% confidence interval 10.6-37.1), 
consisting of 11 persons (of whom five children had attended the same swimming
pool). It remained significant in a sensitivity analysis, strongly supporting the
hypothesis of an environmental source of contamination. This study reveals the
necessity of regular surveillance for hepatitis A and raises the issue of
virological surveys of pool waters.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16207387 [PubMed - indexed for MEDLINE]

292: Clin Infect Dis. 2005 Nov 1;41(9):e86-8. Epub 2005 Sep 21.

Comment in:
    Clin Infect Dis. 2006 Mar 15;42(6):887-8.

Detection of immunoglobulin M antibody to hepatitis A virus in Alaska residents
without other evidence of hepatitis.

Castrodale L, Fiore A, Schmidt T.

Division of Public Health, Alaska Section of Epidemiology, Anchorage, AK
99524-0249, USA. louisa_castrodale@health.state.ak.us

During a 38-month period, 13 of 41 persons with test results positive for IgM
antibody to hepatitis A virus did not meet the case definition for hepatitis A or
have a clear indication for testing, which suggests that test results were
falsely positive. No single testing platform or kit was used. Health care
providers should restrict serologic testing for hepatitis A to patients with
clinical or epidemiologic indications.

PMID: 16206092 [PubMed - indexed for MEDLINE]

293: Transfus Apher Sci. 2005 Nov;33(3):305-9. Epub 2005 Oct 3.

Prevalence of Parvovirus B19 and Hepatitis A virus in Portuguese blood donors.

Henriques I, Monteiro F, Meireles E, Cruz A, Tavares G, Ferreira M, Araújo F.

Department of Transfusion Medicine and Blood Bank, Molecular Biology Centre,
Serviço de Imuno-hemoterapia, Hospital S. João, 4200 Porto, Portugal.

INTRODUCTION: In recent years, concern about the safety of blood in regard to the
transmission of blood-borne viruses has been decreased. Safety has been achieved 
with a combination of different strategies, such as careful selection of donors, 
screening for relevant virological markers and viral inactivation/removal
methods. More recently, the implementation of the nucleic acid amplification
technologies for the detection of HIV-1, HCV and HBV, has increased safety by
reducing the "window period" of the infections. Other viruses, such as Parvovirus
B19 (PB19) and Hepatitis A virus (HAV), can cause problems for blood safety.
These infections could provoke serious complications in some risk groups, such as
pregnant women, patients with hematological problems, children and patients with 
immunodeficiencies. MATERIALS AND METHODS: An observational study was performed
to determine the prevalence of PB19 and HAV in Portuguese blood donors. We
gathered, during four months, 5025 plasma donations and made them into 505 pools 
with no more than 10 donations each. The nucleic acids were isolated using MagNA 
Pure LC (Roche, Mannheim, Germany). A "Real Time PCR" (LightCycler, Roche) was
used to perform the nucleic acid amplification and detection, using kits from the
manufacturer. RESULTS: We found a prevalence of 0.12% for PB19 and 0% for HAV.
Viraemia levels found in the positive donations range from 7.1x10(4) to
2.1x10(12)IU/ml. DISCUSSION: This study demonstrates the possibility of
performing these tests in routine blood banks. We found a similar prevalence of
PB19 when compared with other European and USA countries. In the case of HAV, we 
predict a maximum risk of 0.06% for a donor to be infected. It is necessary to
perform other studies, including cost/benefit analysis to evaluate the risks and 
profits of implementing these methodologies in Transfusion Medicine.

PMID: 16203176 [PubMed - indexed for MEDLINE]

294: Epidemiol Infect. 2006 Jun;134(3):485-91. Epub 2005 Sep 30.

An outbreak of hepatitis A among children and adults in Denmark, August 2002 to
February 2003.

Gervelmeyer A, Nielsen MS, Frey LC, Sckerl H, Damberg E, Mølbak K.

Department of Epidemiology, Statens Serum Institut, Denmark.
a.gervelmeyer@bfr.bund.de

From August 2002 to February 2003 25 cases of hepatitis A were notified from one 
town in Jutland. The first cases were children of three families who returned
from an endemic country. The infection spread subsequently in the local community
and within households. A case-control study among household index cases showed
that hepatitis A was associated with contact to a case in an after-school group
(OR 29.6) and with contact to a case household member in a school class or
day-care centre group (OR 9.5). From a serosurvey it was estimated that for each 
notified patient approximately one additional infection has occurred in the
households. The infection was imported by children of immigrants, born in
Denmark, returning from a visit to friends and relatives in the high-incidence
country of origin of their parents and was then propagated through contact
between children in after-school groups, schools and their families.
Immunoprophylaxis should be given to children prior to visits to friends and
relatives in endemic countries and to case contacts.

PMID: 16194292 [PubMed - indexed for MEDLINE]

295: Epidemiol Infect. 2006 Jun;134(3):492-7. Epub 2005 Sep 30.

The increasing prominence of household transmission of hepatitis A in an area
undergoing a shift in endemicity.

Victor JC, Surdina TY, Suleimeova SZ, Favorov MO, Bell BP, Monto AS.

Department of Epidemiology, School of Public Health, The University of Michigan, 
Ann Arbor, MI 48109, USA. jvictor@umich.edu

In the rapidly developing city of Almaty, Kazakhstan, rates of hepatitis A have
fallen, but no data on prevalence of antibody to hepatitis A virus (anti-HAV)
exist with which to interpret incidence data. In the autumn of 2001, we
determined the anti-HAV prevalence among household and school contacts of
hepatitis A cases. For contacts aged 0-4 years, 5-9 years, 10-14 years, 15-19
years, or 20-30 years, immune prevalences were 9, 12, 33, 33 and 77%
respectively, among immediate-family household contacts and 15, 28, 49, 52 and
77% respectively, among community contacts. Child community contacts were more
likely to be immune than their immediate-family household counterparts (odds
ratio 2.0, 95% confidence interval 1.3-3.2). Almaty is experiencing an
epidemiological shift in hepatitis A incidence. Feasible and effective prevention
strategies using hepatitis A vaccine should be explored.

Publication Types: 
    Research Support, U.S. Gov't, P.H.S.

PMID: 16194291 [PubMed - indexed for MEDLINE]

296: J Gen Virol. 2005 Oct;86(Pt 10):2739-45.

Characterization and genetic variability of Hepatitis A virus genotype IIIA.

Stene-Johansen K, Jonassen TØ, Skaug K.

Division of Infectious Disease Control, Norwegian Institute of Public Health, PO 
Box 4404, Nydalen, NO-0403 Oslo, Norway. kasj@fhi.no

Molecular epidemiological studies of hepatitis A outbreaks in Norway showed the
emergence of Hepatitis A virus (HAV) genotype IIIA in association with parenteral
transmission among haemophiliacs and intravenous drug users. The complete genomic
sequence of one of these outbreak isolates, NOR-21, was determined. This is the
first complete genomic sequence of HAV genotype IIIA. Phylogenetic analysis
showed that genotype IIIA/NOR-21 was genetically distinct from the other human
and simian genotypes. Phylogenetic analysis of the nucleotide sequences clearly
distinguished the different HAV genotypes, regardless of the genomic region used 
for analysis, whereas the amino acid sequences showed a more vague distinction
between human HAV genotypes I and II. In particular, the inferred phylogeny based
on the capsid proteins showed that the human HAV strains were related more
closely to each other than to the simian strains. The greatest variability and
clearest distinction between genotypes were observed for the polymerase gene. The
outbreak isolates of HAV genotype IIIA in this study showed greater nucleotide
variability than is generally seen in outbreaks of genotype I. This high
nucleotide variability, which may be characteristic of this HAV genotype, the
mode of transmission in this outbreak or parallel introductions, is discussed.

PMID: 16186227 [PubMed - indexed for MEDLINE]

297: J Clin Virol. 2006 Jan;35(1):109-12. Epub 2005 Sep 23.

Recurrence of clinically significant hepatitis A following liver transplantation 
for fulminant hepatitis A.

Eisenbach C, Longerich T, Fickenscher H, Schalasta G, Stremmel W, Encke J.

Department of Gastroenterology and Hepatology, University of Heidelberg, Im
Neuenheimer Feld 410, D-69120 Heidelberg, Germany.
Christoph_Eisenbach@med.uni-heidelberg.de

BACKGROUND: We report hepatitis A virus (HAV) infection of a liver allograft
following transplantation for fulminant liver failure due to HAV infection. This 
rare condition has been described in only three patients to date. After liver
transplantation allograft function was good, but starting 80 days after
transplantation, episodes of acute graft dysfunction were observed. OBJECTIVES:
To elucidate the reason for acute hepatic dysfunction a large number of
differential diagnoses were tested. RESULTS: HAV RNA was undetectable for more
than 80 days after transplantation. Detection of genomic HAV RNA by RT-PCR in
serum and stool at the time of graft dysfunction led to the diagnosis of
recurrent HAV infection. CONCLUSIONS: We suggest that the risk of HAV reinfection
after liver transplantation may be far higher than expected as results may be
misinterpreted as rejection episodes.

Publication Types: 
    Case Reports

PMID: 16185915 [PubMed - indexed for MEDLINE]

298: J Med Virol. 2005 Nov;77(3):360-6.

An outbreak of hepatitis A among homeless drug users in Rotterdam, The
Netherlands.

Tjon GM, Götz H, Koek AG, de Zwart O, Mertens PL, Coutinho RA, Bruisten SM.

Municipal Health Service of Amsterdam (Streeklaboratorium voor de
Volksgezondheid), Nieuwe Achtergracht 100, Amsterdam, The Netherlands.

From the end of January to mid-June 2004 (weeks 5-24) a hepatitis A virus (HAV)
outbreak occurred among a homeless and drug user community in Rotterdam, The
Netherlands. To prevent further spread of the virus within this group and to the 
general population, the Municipal Health Service of Rotterdam organized a mass
vaccination campaign during which 83% (1,515/1,800) of the homeless people were
vaccinated. As part of a national HAV typing study, blood and/or fecal samples of
30 Rotterdam HAV IgM+ patients who fell ill during the period of 1 September
2003-1 December 2004 were tested. The tests included RT-PCR and sequencing at the
VP3-VP1 and VP1-P2a regions of the HAV genome. It was found that 12 homeless
people, one family member of a homeless person and two people without a known
risk were infected with a unique subtype 3a strain. Four of the homeless patients
became ill after vaccination and were probably infected at the time. This study
shows that Dutch homeless people and drug users involved in HAV outbreaks should 
be offered HAV vaccine actively to prevent further spread of the infection.
Furthermore, it was shown by molecular techniques that the unique subtype 3a
strain was not found before the Rotterdam outbreak or afterwards, indicating that
the mass vaccination campaign was successful.

PMID: 16173016 [PubMed - indexed for MEDLINE]

299: J Infect Dis. 2005 Oct 15;192(8):1323-30. Epub 2005 Sep 12.

Molecular epidemiology of foodborne hepatitis a outbreaks in the United States,
2003.

Amon JJ, Devasia R, Xia G, Nainan OV, Hall S, Lawson B, Wolthuis JS, Macdonald
PD, Shepard CW, Williams IT, Armstrong GL, Gabel JA, Erwin P, Sheeler L, Kuhnert 
W, Patel P, Vaughan G, Weltman A, Craig AS, Bell BP, Fiore A.

Epidemic Intelligence Service, Epidemiology Program Office and Division of Viral 
Hepatitis, National Center for Infectious Diseases, Centers for Disease Control
and Prevention, Atlanta, Georgia 30333, USA.

BACKGROUND: Molecular epidemiologic investigations can link geographically
separate foodborne hepatitis A outbreaks but have not been used while field
investigations are in progress. In 2003, outbreaks of foodborne hepatitis A were 
reported in multiple states. METHODS: Case-control studies were conducted in 3
states. Hepatitis A virus was sequenced from serologic specimens from individuals
associated with outbreaks and from individuals concurrently ill with hepatitis A 
in non-outbreak settings in the United States and Mexico. RESULTS: Case-control
studies in Tennessee (TN), North Carolina (NC), and Georgia (GA) found green
onions to be associated with illness among restaurant patrons (TN: odds ratio
[OR], 65.5 [95% confidence interval {CI}, 8.9-482.5; NC: OR, 2.4 [95% CI,
0.3-21.9]; GA: OR, 20.9 [95% CI, 3.9-110.3]). Viral sequences from TN case
patients differed by 2 nt, compared with those from case patients in NC and GA. A
third sequence, differing from the TN and GA/NC sequences by 1 nt, was identified
among case patients in a subsequent outbreak in Pennsylvania. Each outbreak
sequence was identical to > or =1 sequence isolated from northern Mexican
resident(s) with hepatitis A. The sources of green onions served in restaurants
in TN and GA were 3 farms in northern Mexico. CONCLUSIONS: Ongoing viral strain
surveillance facilitated the rapid implementation of control measures.
Incorporation of molecular epidemiologic methods into routine hepatitis A
surveillance would improve the detection of hepatitis A outbreaks and increase
our understanding of hepatitis A epidemiology in the United States.

Publication Types: 
    Research Support, U.S. Gov't, P.H.S.

PMID: 16170748 [PubMed - indexed for MEDLINE]

300: Cad Saude Publica. 2005 Sep-Oct;21(5):1531-9. Epub 2005 Sep 12.

Experiments with mathematical models to simulate hepatitis A population dynamics 
under different levels of endemicity.

de Guimaraens MA, Codeço CT.

Instituto de Ciências Biológicas, Universidade de Pernambuco, Recife, Brazil.

Heterogeneous access to sanitation services is a characteristic of communities in
Brazil. This heterogeneity leads to different patterns of hepatitis A endemicity:
areas with low infection rates have higher probability of outbreaks, and areas
with higher infection rates have high prevalence and low risk of outbreaks. Here 
we develop a mathematical model to study the effect of variable exposure to
infection on the epidemiological dynamics of hepatitis A. Differential equations 
were used to simulate population dynamics and were numerically solved using the
software Stella. The model uses parameters from serological surveys in the
Greater Metropolitan Rio de Janeiro, in areas with different sanitation
conditions. Computer simulation experiments show that the range of infection
rates observed in these communities are characteristic of high and low levels of 
hepatitis A endemicity. We also found that the functional relationship between
sanitation and exposure to infection is an important component of the model. The 
analysis of the public health impact of partial sanitation requires a better
understanding of this relationship.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16158159 [PubMed - indexed for MEDLINE]

301: Clin Microbiol Infect. 2005 Oct;11(10):845-8.

Changing epidemiology of hepatitis A in the Bologna metropolitan area, northern
Italy: importance of counselling and prophylactic measures for the male
homo/bisexual population.

Manfredi R, Calza L, Chiodo F.

Department of Clinical and Experimental Medicine, Division of Infectious
Diseases, University of Bologna 'Alma Mater Studiorum', S. Orsola Hospital,
Bologna, Italy. manfredi@med.unibo.it

During a 6-year observational study, 122 cases of hepatitis A virus (HAV)
infection were detected in Bologna, Italy, with a c. 300% increase in cases
between 1999 and 2004. There were 104 cases (85.2%) in male adults, of whom
nearly 70% had unprotected sexual contact as the probable risk-factor. There were
increasing numbers of cases in immigrants between 1999 and 2004 (p 0.036), and
concurrent cases of infection with human immunodeficiency virus, hepatitis B and 
C viruses and syphilis were also noted in adult males (p 0.0032). There is a need
to re-emphasise targeted educational programmes and anti-HAV vaccination for
at-risk subjects.

PMID: 16153262 [PubMed - indexed for MEDLINE]

302: J Neuroophthalmol. 2005 Sep;25(3):189-92.

Necrobiotic xanthogranuloma associated with choroidal infiltration and syncytial 
giant cell hepatitis.

Amer R, Pe'er J, Pappo O, Dotan S.

Department of Ophthalmology, Hadassah-Hebrew University Medical Center,
Jerusalem, Israel. radgondeamer@yahoo.com

A 31-year-old woman developed necrobiotic xanthogranuloma (NXG), a thickened
choroid, and syncytial giant cell hepatitis, a previously unreported association.
NXG and syncytial giant cell hepatitis may have a common autoimmune pathogenesis.

Publication Types: 
    Case Reports

PMID: 16148625 [PubMed - indexed for MEDLINE]

303: Ann Univ Mariae Curie Sklodowska [Med]. 2004;59(1):209-13.

Dynamics of proinflammatory cytokines serum levels during viral hepatitis type A.

Fota-Markowska H, Modrzewska R, Rolla-Szczepańska R, Bielec D, Krzowska-Firych J.

Chair and Department of Infectious Diseases, Skubiszewski Medical University of
Lublin.

In this study we assessed the dynamics concerning IL-2, sLL-2R and IL-4 serum
levels in the course of an acute viral hepatitis A infection. The study group
consisted of 48 persons. The serum concentrations of IL-2, sIL-2R and IL-4 were
assessed with the use of ELISA methods. In patients the assessments were done
twice--in the first and third week of the hospitalisation. In the control group, 
which consisted of 24 healthy persons the assessments were done once. The
obtained data were analysed with the use of c-Cochran and Cox statistical test.
We observed a statistically important decrease in IL-2 and IL-4 serum levels in
patients with acute viral hepatitis A infection in the first week of the
hospitalisation compared to values observed in the control group. We also
observed an increase in sIL-2R levels in the course of the disease. The dynamics 
of IL-2, sIL-2R and IL-4 serum levels in patients with acute hepatitis A
infection was of a random type. The assessment of IL-2, sIL-2R and IL-4 serum
levels can be helpful in examining the cellular response in viral hepatitis A
infection.

PMID: 16145982 [PubMed - indexed for MEDLINE]

304: J Hepatol. 2005 Dec;43(6):958-64. Epub 2005 Jul 11.

An outbreak of hepatitis A virus infection with a high case-fatality rate among
injecting drug users.

Spada E, Genovese D, Tosti ME, Mariano A, Cuccuini M, Proietti L, Giuli CD,
Lavagna A, Crapa GE, Morace G, Taffon S, Mele A, Rezza G, Rapicetta M.

Istituto Superiore di Sanità, National Center of Epidemiology, Surveillance and
Health Promotion, Clinical Epidemiology Unit, Viale Regina Elena 299, 00161 Rome,
Italy. spada@iss.it

BACKGROUND/AIMS: In 2002, the first reported outbreak of hepatitis A virus (HAV) 
infection involving mostly intravenous drug users (IDU) occurred in Italy. We
attempted a thorough evaluation of the outbreak, including epidemiological,
clinical and virological analyses. METHODS: We conducted an epidemiological
investigation, including a case-control study, to identify the source and the
modes of HAV transmission. Hepatitis B and C (HCV) viruses and human
immunodeficiency virus (HIV) coinfections were clinically analysed. Sequence
analysis of the VP1/2A junction of the HAV isolates was also performed. RESULTS: 
Of the 47 symptomatic cases, 35 were IDUs. The only associated risk factor was
contact (not related to injecting practices) with a jaundiced person (odds ratio:
5.8; 95% confidence interval: 1.3-29.9). Of the cases, 58% were anti-HCV positive
and 4.7% anti-HIV positive. Three individuals died of acute liver failure: 2 were
HCV-coinfected alcohol abusers, with underlying liver cirrhosis; 1 was
HCV/HIV-coinfected. HAV-RNA was found in 15 of the 24 tested patients: genotype
IB (8 cases) and IIIA (7 cases) were detected. CONCLUSIONS: HAV was probably
transmitted through the fecal-oral route, although parenteral transmission cannot
be excluded. The high fatality rate was probably due to severe underlying liver
damage. The occurrence of this outbreak highlights the need for routine HAV
vaccination for IDUs.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16143420 [PubMed - indexed for MEDLINE]

305: Clin Infect Dis. 2005 Oct 1;41(7):1020-6. Epub 2005 Aug 29.

Hepatitis A and B booster recommendations: implications for travelers.

Zuckerman JN, Connor BA, von Sonnenburg F.

Academic Centre for Travel Medicine and Vaccines and Royal Free Travel Health
Centre, World Health Organization Collaborating Centre for Travel Medicine, Royal
Free and University College Medical School, London, United Kingdom.
j.zuckerman@medsch.ucl.ac.uk

Hepatitis A and B are serious vaccine-preventable diseases with a predominantly
overlapping epidemiological distribution. Travelers, a term encompassing a range 
of individuals, are at risk of contracting these diseases if they are
unvaccinated. Although the benefits of the primary vaccination course of
hepatitis A and B vaccines are clear, the administration of hepatitis A and B
boosters varies worldwide. Recommendations on the need for booster vaccinations
have recently been published, and the implications of these recommendations for
travelers are discussed in this review. Until a greater understanding is reached 
on the immunogenicity of hepatitis A and B vaccines in certain special groups
(e.g., immunocompromised persons), there will be a need to monitor antibody
levels to assess whether booster vaccinations are required. However, for the
majority of immunocompetent travelers, the full primary vaccination course will
provide protection from both hepatitis A and B infection in the long term,
without the need for boosters.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 16142669 [PubMed - indexed for MEDLINE]

306: N Engl J Med. 2005 Sep 1;353(9):890-7.

Comment in:
    N Engl J Med. 2005 Nov 24;353(21):2300-1.    N Engl J Med. 2005 Nov 24;353(21):2300-1.    N Engl J Med. 2005 Sep 1;353(9):944-6.

An outbreak of hepatitis A associated with green onions.

Wheeler C, Vogt TM, Armstrong GL, Vaughan G, Weltman A, Nainan OV, Dato V, Xia G,
Waller K, Amon J, Lee TM, Highbaugh-Battle A, Hembree C, Evenson S, Ruta MA,
Williams IT, Fiore AE, Bell BP.

Epidemic Intelligence Service, Centers for Disease Control and Prevention,
Atlanta, GA 30333, USA.

BACKGROUND: In November 2003, a large hepatitis A outbreak was identified among
patrons of a single Pennsylvania restaurant. We investigated the cause of the
outbreak and factors that contributed to its unprecedented size. METHODS:
Demographic and clinical outcome data were collected from patients with
laboratory confirmation of hepatitis A, and restaurant workers were tested for
hepatitis A. A case-control study was conducted among patrons who dined at the
restaurant between October 3 and October 6, 2003. Sequence analysis was performed
on a 315-nucleotide region of viral RNA extracted from serum specimens. RESULTS: 
Of 601 patients identified, 3 died; at least 124 were hospitalized. Of 425
patients who recalled a single dining date at the restaurant, 356 (84 percent)
had dined there between October 3 and October 6. Among 240 patients in the
case-control study, 218 had eaten mild salsa (91 percent), as compared with 45 of
130 controls (35 percent) (odds ratio, 19.6; 95 percent confidence interval, 11.0
to 34.9) for whom data were available. A total of 98 percent of patients and 58
percent of controls reported having eaten a menu item containing green onions
(odds ratio, 33.3; 95 percent confidence interval, 12.8 to 86.2). All restaurant 
workers were tested, but none were identified who could have been the source of
the outbreak. Sequences of hepatitis A virus from all 170 patients who were
tested were identical. Mild salsa, which contained green onions grown in Mexico, 
was prepared in large batches at the restaurant and provided to all patrons.
CONCLUSIONS: Green onions that were apparently contaminated before arrival at the
restaurant caused this unusually large foodborne outbreak of hepatitis A. The
inclusion of contaminated green onions in large batches that were served to all
customers contributed to the size of the outbreak. Copyright 2005 Massachusetts
Medical Society.

PMID: 16135833 [PubMed - indexed for MEDLINE]

307: Expert Rev Vaccines. 2005 Aug;4(4):459-71.

Prevention of hepatitis A by Havrix: a review.

Van Herck K, Van Damme P.

Centre for the Evaluation of Vaccination, WHO Collaborating Centre for the
Prevention and Control of Viral Hepatitis, University of Antwerp,
Universiteitsplein 1, 2610 Wilrijk, Belgium. koen.vanherck@ua.ac.be

Hepatitis A is one of the most common vaccine-preventable infectious diseases in 
the world. With at least 1.5 million cases of hepatitis A worldwide each year,
disease management constitutes a substantial economic burden. The first effective
vaccine against hepatitis A, Havrix was introduced in 1992. This review
summarizes data accumulated following more than a decade of clinical experience
with this vaccine and compares clinical data with other currently available
hepatitis A vaccines. Based on this data and on the current immunological
knowledge, a recent consensus concluded that hepatitis A vaccines induce lifelong
protection, and thus booster vaccinations against hepatitis A are unnecessary in 
fully immunized, healthy people. In view of this, current regulatory
recommendations for the use of hepatitis A vaccines are reviewed and possible
future strategies identified.

Publication Types: 
    Review

PMID: 16117704 [PubMed - indexed for MEDLINE]

308: Ceylon Med J. 2005 Jun;50(2):54-8.

Seroprevalence of hepatitis A antibodies in relation to social factors--a
preliminary study.

de Silva KS, Weerasuriya DC, Peelawattage M, Fernando S.

Department of Paediatrics, Faculty of Medicine, Colombo.
shamyadesilva@hotmail.com

INTRODUCTION: Hepatitis A is a benign illness in children with the rare
possibility of fatal complications. Although an endemic disease, very few studies
have been done in children regarding the seroprevalence of hepatitis A antibodies
in Sri Lanka. OBJECTIVES: (i) To document the seropositivity for hepatitis A in a
group of children admitted to a paediatric ward. (ii) To determine the
relationship of hepatitis A viral infection to social factors in these children. 
METHOD: A prospective, descriptive, cross-sectional study was carried out in a
ward at the Lady Ridgeway Hospital for 7 months from September 2001. Children
admitted on predetermined days, needing venepuncture for their presenting
illness, were studied while those who were seriously ill were excluded. Written
consent was obtained and a questionnaire with details of socio-economic
conditions, personal hygiene practices of the mother, access to water and
sanitation and health related behaviour was administered. Total antibodies to
hepatitis A were detected by ELISA on a sample of blood taken from each patient. 
RESULTS: Two hundred and eighty eight samples of blood were analysed. None of the
children were immunised against hepatitis A. There were 158 boys (54.9%). Thirty 
one (10.8%) of the 288 patients had antibodies against hepatitis A. The
seroprevalence was 11.6% in children under 10 years of age. Majority (78%) were
from families with a monthly income of less than Rs 10,000/-. Fifteen (48.4%) of 
the 31 seropositive children were from families earning less than Rs 5000/- per
month. Belonging to social classes IV and V and having mothers with only primary 
education were factors significantly associated with seropositivity. No
significant difference in the presence of antibodies was observed regarding the
personal hygiene practices analysed and access to basic amenities. Health related
behaviour practices analysed were significantly associated with the presence of
hepatitis A antibodies. CONCLUSIONS: Seroprevalence of 10.8% was observed in a
selected group of children. Factors such as poor socio-economic background and
having mothers with only primary education were associated with hepatitis A virus
(HAV) antibodies as were certain health related behaviour practices of children.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16114769 [PubMed - indexed for MEDLINE]

309: South Med J. 2005 Jul;98(7):723-5.

Reversible encephalopathy secondary to paratyphoid infection and concomitant
acute Hepatitis A.

El-Khoury M, Naoushi H, Sawaya R, Aoun E, Nassar NT, Sharara AI.

Department of Internal Medicine, Divisions of Infectious Diseases, Neurology and 
Gastroenterology, American University of Beirut Medical Center, Beirut, Lebanon.

Reversible encephalopathy has been described in association with typhoid fever as
well as nontyphoidal salmonella infections. A diagnostic dilemma as to the cause 
of encephalopathy may arise when there is coexistent acute viral hepatitis and
suspicion of fulminant liver failure. The authors report a patient who presented 
with acute icteric hepatitis A infection and a concomitant febrile illness due to
Salmonella paratyphi associated with progressive encephalopathy and coma. The
young man developed high-grade fever and coma. Concomitant infection with S.
paratyphi was diagnosed and the patient's encephalopathy resolved rapidly with
antibiotic therapy. This is the first report of a putative association of S.
paratyphi infection and reversible encephalopathy. Salmonella and hepatitis A
virus infection are both transmitted via the fecal-oral route, and awareness of
this association is important in the management of such patients.

Publication Types: 
    Case Reports

PMID: 16108242 [PubMed - indexed for MEDLINE]

310: Med J Malaysia. 2005 Jul;60 Suppl B:112-5.

Hepatitis A vaccines.

Shahidah KN.

National Institute for Natural Products, Vaccines & Biologicals, Ministry of
Health Malaysia, Malaysia.

Hepatitis A, an acute usually self limiting infection of the liver is one of the 
most common vaccine-preventable infectious disease in the world. Effective
vaccines which provide long term immunity against hepatitis A have been available
since 1992. They are of known good quality, well tolerated with no serious
adverse events and have been successfully used to protect different populations
from infection as well as interrupt outbreak in closed communities. Mathematical 
models estimate the long term persistence of antiHAV antibodies to be more than
25 years. Vaccination efforts should be supplemented by health education and
improved sanitation. Planning for large scale immunization programmes against
hepatitis A should take into consideration epidemiological and cost benefit
studies.

Publication Types: 
    Review

PMID: 16108190 [PubMed - indexed for MEDLINE]

311: Hepatology. 2005 Sep;42(3):688-95.

Susceptibility to hepatitis A in patients with chronic liver disease due to
hepatitis C virus infection: missed opportunities for vaccination.

Shim M, Khaykis I, Park J, Bini EJ.

Department of Medicine and Division of Gastroenterology, VA New York Harbor
Healthcare System and NYU School of Medicine, New York, NY 10010, USA.

Hepatitis A virus (HAV) superinfection is associated with a high risk of liver
failure and death in patients with underlying chronic liver disease. Although HAV
vaccination is recommended for all patients with chronic hepatitis C virus (HCV) 
infection, little is known about adherence to these recommendations in clinical
practice. The aims of this study were to determine the frequency of HAV testing
and vaccination among patients with chronic HCV infection. We conducted a
retrospective cohort study of 1,193 patients diagnosed with chronic HCV infection
over a 1-year period. During 1,646 person-years of follow-up, patients were seen 
by their primary care provider a median of 10.0 times (interquartile range,
4.0-20.0). HAV antibody testing was performed in 640 subjects (53.6%), and 317
(49.5%) of those tested were susceptible (HAV antibody negative). Only 94 of the 
1,193 patients (7.9%) received the HAV vaccine, including 26.8% of the 317
susceptible patients, 0.9% of the 323 patients who were already immune to HAV,
and 1.1% of the 553 subjects who were never tested. Among the 94 vaccinated
patients, 45 received only one dose of the vaccine. Three of the unvaccinated
patients developed acute HAV infection during follow-up, and 1 of them died of
acute liver failure. In conclusion, despite published recommendations to
vaccinate against HAV in patients with chronic HCV infection, we found that HAV
testing and vaccination rates were low in clinical practice. Public health
programs to increase awareness about HAV vaccination in patients with chronic
liver disease are needed.

Publication Types: 
    Multicenter Study

PMID: 16104047 [PubMed - indexed for MEDLINE]

312: Am J Trop Med Hyg. 2005 Aug;73(2):457-9.

Decline of maternal hepatitis a antibodies during the first 2 years of life in
infants born in Turkey.

Derya A, Necmi A, Emre A, Akgün Y.

Infectious Disease Unit, Department of Pediatrics, Cukurova University Faculty of
Medicine, Balcali, Adana, Turkey. deryaalabaz@yahoo.como

Selective immunization of at-risk groups may reduce the incidence of hepatitis A 
infection, but only the inclusion of hepatitis A vaccine in a routine universal
childhood immunization schedule would guarantee control of the infection. But the
interference by maternally derived hepatitis A antibodies (anti-HAV) with the
immunogenicity of inactivated hepatitis A vaccine is still important in the
determination of the optimal age for hepatitis A vaccination. The hepatitis A
vaccines have not been assessed widely in children under the age of 2 years and
are not currently licensed for this age group in many countries. A prospective
trial was performed to detect seroprevalence of maternal hepatitis A antibodies
during the first 2 years of life among young infants born to hepatitis A antibody
positive mothers in Turkey. We measured at-birth anti-HAV in 147 infants born in 
our hospital and in their mothers and then from the offspring at months 3, 6, 9, 
12, 15, 18, 21, and 24. The prevalence of seropositivity among the mothers at
birth were found similarly high (93.9%) to the studies previously done among the 
adults in our area. The prevalence of anti-HAV among children aged 0, 9, 12, 15, 
18, and 21 months were 93.9%, 62.6%, 36.1%, 13.6%, 6.1%, and 0.7%, respectively. 
Although a proportion of infants still had measurable antibodies at 9 and 12
month of age, two thirds of the infants over the age of 12 months were at high
risk of acquiring hepatitis A infection, as living in a endemic region.

PMID: 16103622 [PubMed - indexed for MEDLINE]

313: Am J Trop Med Hyg. 2005 Aug;73(2):453-6.

Hepatitis a in Lebanon: a changing epidemiological pattern.

Sacy RG, Haddad M, Baasiri G, Khoriati A, Gerbaka BJ, Abu-Elyazeed R.

St. Georges Hospital, Beirut, Lebanon.

In this multicenter study in Lebanon, hepatitis A virus (HAV) seroprevalence
rates were surveyed by age, gender, and socioeconomic factors. Blood samples
collected from 606 subjects aged 1 to 30 years were analyzed for anti-HAV IgG.
Age was the most important factor influencing HAV seroprevalence. HAV
seroprevalence rates in the current study were about 78% in the > or = 21 years
age group, 28% in the 6-10 years age group, and 11% in the 1-5 years age group as
compared with 97.7% in adults, 85% in children aged 6-12 years, and 40% in
children aged 1 to 5 years in previous studies, demonstrating a shift in HAV
seroprevalence from the younger to the higher age groups. In light of the
severity of the disease in adults and availability of safe and effective vaccines
against HAV infection, introduction of HAV vaccination into the national
immunization schedule of Lebanon should be considered.

Publication Types: 
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 16103621 [PubMed - indexed for MEDLINE]

314: J Virol. 2005 Sep;79(17):10968-77.

Hepatitis A virus suppresses RIG-I-mediated IRF-3 activation to block induction
of beta interferon.

Fensterl V, Grotheer D, Berk I, Schlemminger S, Vallbracht A, Dotzauer A.

Department of Virology, University of Bremen, Germany.

Hepatitis A virus (HAV) antagonizes the innate immune response by inhibition of
double-stranded RNA (dsRNA)-induced beta interferon (IFN-beta) gene expression.
In this report, we show that this is due to an interaction of HAV with the
intracellular dsRNA-induced retinoic acid-inducible gene I (RIG-I)-mediated
signaling pathway upstream of the kinases responsible for interferon regulatory
factor 3 (IRF-3) phosphorylation (TBK1 and IKKepsilon). In consequence, IRF-3 is 
not activated for nuclear translocation and gene induction. In addition, we found
that HAV reduces TRIF (TIR domain-containing adaptor inducing IFN-beta)-mediated 
IRF-3 activation, which is part of the Toll-like receptor 3 signaling pathway. As
IRF-3 is necessary for IFN-beta transcription, inhibition of this factor results 
in efficient suppression of IFN-beta synthesis. This ability of HAV seems to be
of considerable importance for HAV replication, as HAV is not resistant to
IFN-beta, and it may allow the virus to establish infection and preserve the
sites of virus production in later stages of the infection.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16103148 [PubMed - indexed for MEDLINE]

315: Health Policy. 2005 Sep 28;74(1):39-45. Epub 2005 Jan 12.

Hepatitis A and B seropositivity among medical students.

Oncu S, Oncu S, Sakarya S.

Department of Infectious Diseases and Clinical Microbiology, Adnan Menderes
University Medical Faculty, 09100 Aydin, Turkey. serkanoncu@hotmail.com

OBJECTIVE: Health science students are commonly exposed to some infectious
agents, including hepatitis A virus (HAV) and hepatitis B virus (HBV), which may 
cause substantial morbidity and even deaths. The identification of prevalence and
risk factors is essential for implementing efficacious preventive measures. A
serological survey was performed among medical students of Adnan Menderes
University Medical Faculty to determine the prevalence of antibodies against HAV 
and HBV, and, as a secondary objective, to determine risk factors for acquisition
of these infections. METHODS: Nearly all students were included in the study. All
participants completed a structured questionnaire that assessed demographic and
socio-economic characteristics. Anti-HAV IgG, anti-HBc IgG, HbsAg and anti-HBs
were tested using commercially available Elisa kits. RESULTS: A total of 247
students, 146 (59.1%) male and 101 (40.9%) female, were included in the study.
The prevalence of anti-HAV IgG was detected as 64%. Number of siblings and place 
of residence were detected as independent factors affecting the anti-HAV
seropositivity. The prevalence of anti-HBc IgG was detected as 7.3%. Among the
students positive for anti-HBc IgG, 5 (2%) students were HBsAg positive and the
other 13 (5.3%) were anti-HBs positive. HBV infection in household members, risky
sexual behaviour and vaccination were independent factors affecting the
prevalence of anti-HBc IgG positivity. CONCLUSIONS: The high susceptibility of
medical students and their increased risk of clinical HAV and HBV infection
identify a need for primary prevention through the administration of vaccination 
in this group in western Turkey.

PMID: 16098410 [PubMed - indexed for MEDLINE]

316: Eur J Public Health. 2005 Oct;15(5):464-6. Epub 2005 Aug 10.

Prevalence of hepatitis A among drug users in north-eastern Italy. Is vaccination
necessary in low prevalence areas?

Lugoboni F, Quaglio G, Pajusco B, Foroni M, Blengio G, Talamini G, Mezzelani P,
Des Jarlais DC.

Medical Service for Addictive Disorders, Department of Internal Medicine,
University of Verona, Italy. paolo.mezzelani@univr.it

BACKGROUND: The authors report on the prevalence of, and risk factors for,
hepatitis A virus (HAV) in a group of drug users in Italy. METHODS: 404 heroin
users were recruited and compared with a control group of 107 subjects in the
general population. RESULTS: Drug users born in north-eastern Italy have a
prevalence of anti-HAV similar to the control group. A much higher prevalence was
found in drug users born in southern Italy. CONCLUSION: The similar prevalence of
anti-HAV in drug users born in north-eastern Italy and in the general population,
suggests that their lifestyle does not involve a substantial additional risk of
HAV. The much higher prevalence found in drug users born in southern Italy is
more likely to be related to infection during infancy.

Publication Types: 
    Comparative Study

PMID: 16093301 [PubMed - indexed for MEDLINE]

317: J Formos Med Assoc. 2005 Jul;104(7):507-10.

Successful treatment of acute hepatitis A-associated hemophagocytic syndrome by
intravenous immunoglobulin.

Tai CM, Liu CJ, Yao M.

Division of Gastroenterology, Department of Internal Medicine, National Taiwan
University Hospital, College of Medicine, National Taiwan University, Taipei.

Virus-associated hemophagocytic syndrome (VAHS) is a rare complication in acute
hepatitis A virus (HAV) infection. There is no standard therapy for VAHS and the 
clinical course is variable. Data on the use of intravenous immunoglobulin (IVIG)
in the treatment of HAV-associated VAHS is limited. We report a previously
healthy, 32-year-old man who presented with general malaise, fever, chills and
splenomegaly. Laboratory examination showed marked elevation of aminotransferase,
leukopenia and thrombocytopenia. Acute hepatitis A was documented by the presence
of immunoglobulin M anti-HAV and compatible liver biopsy findings. Bone marrow
examination revealed extensive hemophagocytosis. IVIG was administered after the 
diagnosis of HAV-associated VAHS. His symptoms and laboratory abnormalities
improved, and following a smooth recovery he was discharged 1 month after
admission.

Publication Types: 
    Case Reports

PMID: 16091828 [PubMed - indexed for MEDLINE]

318: Euro Surveill. 2005 May;10(5):111-4.

Comment in:
    Euro Surveill. 2005 May;10(5):74.

Hepatitis A outbreak among MSM linked to casual sex and gay saunas in Copenhagen,
Denmark.

Mazick A, Howitz M, Rex S, Jensen IP, Weis N, Katzenstein TL, Haff J, Molbak K.

European Programme for Intervention Epidemiology Training (EPIET), Department of 
Epidemiology, Statens Serum Institut, Denmark.

During an outbreak of hepatitis A predominantly among men who have sex with men
(MSM) in Copenhagen, Denmark, in 2004, we did a case-control study to determine
risk factors for infection. A case was an MSM >17 years, living in Copenhagen,
with IgM positive hepatitis A infection diagnosed between June and August 2004,
and without a household contact with a hepatitis A case before onset of illness. 
Controls were selected at the Copenhagen Pride Festival. The study included 18
cases and 64 controls. Sixteen of 18 cases and 36/63 controls had sex with casual
partners (ORMH 5.6, 95% CI 1.2-26.9). Eleven of 18 cases and 14/62 controls had
sex in gay saunas (ORMH 4.2, 95% CI 1.5-11.5). Sex at private homes appeared to
be protective (ORMH 0.2, 95% CI 0.1-0.7). Casual sex including sex in gay saunas 
was an important risk factor for the spread of HAV among MSM in Copenhagen. The
results are in accordance with findings in other European outbreaks. As the
general immunity to hepatitis A decreases and the outbreak potential increases,
we recommend health education and hepatitis A vaccination to all MSM not living
in monogamous relationships, especially if they visit gay saunas or other places 
with frequent partner change. To stop spread of hepatitis A among MSM in Europe, 
a European consensus on prevention and control measures may be required.

PMID: 16077208 [PubMed - indexed for MEDLINE]

319: Vaccine. 2005 Oct 17;23(43):5099-105.

Reactogenicity and immunogenicity profile of a two-dose combined hepatitis A and 
B vaccine in 1-11-year-old children.

Roberton D, Marshall H, Nolan TM, Sokal E, Díez-Domingo J, Flodmark CE, Rombo L, 
Lewald G, Flor Jde L, Casanovas JM, Verdaguer J, Marés J, Esso DV, Dieussaert I, 
Stoffel M.

Department of Paediatrics, Children, Youth and Women's Health Service, North
Adelaide SA 5006, Australia. don.roberton@adelaide.edu.au

This study was conducted to compare the reactogenicity, immunogenicity and safety
of a combined two-dose (0, 6 months) hepatitis A and B vaccine (720ELU HAV, 20
mcg HBsAg) with the established three-dose (0, 1 and 6 months) hepatitis A and B 
vaccine (360ELU HAV, 10 mcg HBsAg). A total of 511 children aged 1-11 years who
had not previously received a hepatitis A or B vaccine were enrolled in the
study. Both vaccines were well tolerated, and were shown to be safe and
immunogenic. The analysis, stratified according to two age groups (1-5 year and
6-11-year-old children) demonstrated that the reactogenicity profile of the
two-dose schedule was at least as good as that of the established schedule. Both 
vaccines and schedules provided at least 98% seroprotection against hepatitis B
and 100% seroconversion against hepatitis A, 1 month after the end of the
vaccination course (Month 7).

Publication Types: 
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial

PMID: 16055231 [PubMed - indexed for MEDLINE]

320: J Gastroenterol Hepatol. 2005 Aug;20(8):1165-75.

Influence of load of hepatitis A virus on disease severity and its relationship
with clinical manifestations in patients with hepatitis A.

Sainokami S, Abe K, Ishikawa K, Suzuki K.

First Department of Internal Medicine, Iwate Medical University, Iwate, Japan.
sainokami@mizhsp-iwate.jp

BACKGROUND AND AIM: The purpose of the present study was to investigate the
influence of viral load on disease severity and analyze the possible relationship
of the load of hepatitis A virus (HAV) with disease severity and laboratory
findings. METHODS: Fifty-eight patients diagnosed with acute hepatitis A were
used in the current study, of whom 12 patients progressed to severe acute
hepatitis (s-AH) defined on the basis of a prothrombin time (PT) of <40% and 46
patients were diagnosed as having mild acute hepatitis (m-AH). The load of HAV
was measured with real-time polymerase chain reaction. RESULTS: Peak viral load
showed a significant correlation with alanine aminotransferase (ALT) (r = 0.363, 
P = 0.0048) and PT levels (r = -0.330, P = 0.0110). In terms of disease severity,
there was a significant correlation with ALT (r = 0.462, P = 0.0012) and PT
levels (r = 0.400, P = 0.0059) in the m-AH group, but not in the s-AH group. A
significant positive correlation of peak viral load with the C-reactive protein
level (r = 0.270, P = 0.0400) and a significant negative correlation of peak
viral load with the platelet count (r = -0.313, P = 0.0015) was also found.
CONCLUSIONS: The load of HAV was closely correlated with liver damage and disease
severity in m-AH, but not in s-AH. The load of HAV was also closely associated
with the increase in C-reactive protein level and enhancement of
thrombocytopenia.

PMID: 16048563 [PubMed - indexed for MEDLINE]

321: Am J Trop Med Hyg. 2005 Jul;73(1):40-3.

Age-specific seroprevalence of hepatitis a among school children in central
Tunisia.

Letaief A, Kaabia N, Gaha R, Bousaadia A, Lazrag F, Trabelsi H, Ghannem H, Jemni 
L.

Department of Internal Medicine and Infectious Diseases Unit, Microbiology Unit, 
and Epidemiology Unit, University Hospital Farhat Hached, Sousse, Tunisia.
amel.letaief@famso.rnu.tn

Hepatitis A virus (HAV) has different epidemiologic and clinical patterns,
depending on the level of endemicity in a given geographic area. Tunisia is
considered a region of high endemicity for hepatitis. Improvement of
socioeconomic conditions in this country has made a determination of the
seroprevalence of this disease advisable. We assessed the seroprevalence of HAV
in Sousse in central Tunisia. A total of 2,400 school children 5-20 years of age 
(mean +/- SD age = 11.7 +/- 3.5 years) were selected by two-stage cluster
sampling and tested serologically for IgG antibody to HAV by using an
enzyme-linked immunosorbent assay. The overall seroprevalence among this
population was 60% (44%, in children < 10 years old, 58% in those 10-15 years of 
age, and 83% in those > 15 years of age. Seroprevalence also varied according to 
area of residence. At the age of 10, 21.3% of school children living in the urban
areas and 87.7% of those living in rural areas had antibodies to HAV. Other
factors that increased seroprevalence included non-potable water, crowding, and a
low education level of parents with odds ratios of 4.37, 2.96, and 2.62,
respectively. This study has shown an increase of seroprevalence with age,
suggesting that transmission among younger children has decreased, particularly
in urban areas. Programs to prevent hepatitis A may need to be modified based
upon the changing age distribution of the disease and mass vaccination program
could be indicated if additional incidence and prevalence data confirm the
intermediate endemicity of HAV.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16014829 [PubMed - indexed for MEDLINE]

322: JAMA. 2005 Jul 13;294(2):202-10.

Comment in:
    JAMA. 2005 Jul 13;294(2):246-8.    JAMA. 2006 Jan 18;295(3):282; author reply 282.

Incidence of hepatitis A in Israel following universal immunization of toddlers.

Dagan R, Leventhal A, Anis E, Slater P, Ashur Y, Shouval D.

Pediatric Infectious Disease Unit, Soroka University Medical Center and the
Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva,
Israel. rdagan@bgu.ac.il

CONTEXT: In Israel, the mean annual incidence of hepatitis A disease was 50.4 per
100 000 during 1993-1998. A 2-dose universal hepatitis A immunization program
aimed at children aged 18 and 24 months (without a catch-up campaign) was started
in 1999. OBJECTIVE: To observe the impact of toddlers-only universal vaccination 
on hepatitis A virus disease in Israel. DESIGN AND SETTING: Ongoing passive
national surveillance of hepatitis A cases in Israel has been conducted since
1993 by the Ministry of Health. An active surveillance program in the Jerusalem
district in 1999-2003 provided validation for the passive program. MAIN OUTCOME
MEASURE: Incidence of reported hepatitis A disease, 1993-2004. RESULTS: Overall
vaccine coverage in Israel in 2001-2002 was 90% for the first dose and 85% for
the second dose. A decline in disease rates was observed before 1999 among the
Jewish but not the non-Jewish population. After initiation of the program, a
sharp decrease in disease rates was observed in both populations. The annual
incidence of 2.2 to 2.5 per 100 000 during 2002-2004 represents a 95% or greater 
reduction for each year with respect to the mean incidence during 1993-1998
(P<.001). For children aged 1 through 4 years, a 98.2% reduction in disease was
observed in 2002-2004, compared with the prevaccination period (P<.001). However,
a sharp decline was also observed in all other age groups (84.3% [<1 year], 96.5%
[5-9 years], 95.2% [10-14 years], 91.3% [15-44 years], 90.6% [45-64 years], and
77.3% [>or=65 years]). Among the Jewish population in the Jerusalem district, in 
whom the active surveillance program was successfully conducted, a more than 90% 
reduction of disease was demonstrated. Of the 433 cases reported nationwide in
2002-2004 in whom vaccination status could be ascertained, 424 (97.9%) received
no vaccine and none received 2 doses. CONCLUSION: This universal toddlers-only
immunization program in Israel demonstrated not only high effectiveness of
hepatitis A vaccination but also marked herd protection, challenging the need for
catch-up hepatitis A vaccination programs.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16014594 [PubMed - indexed for MEDLINE]

323: JAMA. 2005 Jul 13;294(2):194-201.

Comment in:
    JAMA. 2005 Jul 13;294(2):246-8.    JAMA. 2006 Jan 18;295(3):282; author reply 282.

Incidence of hepatitis A in the United States in the era of vaccination.

Wasley A, Samandari T, Bell BP.

Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta,
GA 30333, USA. awasley@cdc.gov

CONTEXT: In the United States, hepatitis A is a frequently reported
vaccine-preventable disease. Vaccination has been recommended for persons at
increased risk since 1996. In 1999, it was recommended that children living in 11
states with the highest incidence of hepatitis A be routinely vaccinated, and
that children living in 6 additional states, with incidence above the national
average, be considered for routine vaccination. OBJECTIVE: To assess impact of
the current vaccination strategy by evaluating trends in reported cases of
hepatitis A since implementation. DESIGN, SETTING, AND CASES: A longitudinal
analysis of characteristics of cases of hepatitis A reported in the United States
since 1990 to the National Notifiable Diseases Surveillance System. MAIN OUTCOME 
MEASURE: Incidence rates of reported cases of hepatitis A. Incidence rates in
2003 were compared with those for the prevaccination baseline period (1990-1997) 
overall and in the 17 states in which children should be routinely vaccinated or 
considered for routine vaccination (vaccinating states). Incidence rates in
vaccinating states were also compared with those in the remaining states where
there is no recommendation for statewide vaccination of children (nonvaccinating 
states). RESULTS: Between the baseline period (1990-1997) and 2003, overall
hepatitis A rates declined 76% to 2.6 per 100,000, significantly lower than
previous nadirs in 1983 (9.2/100,000) and 1992 (9.1/ 100,000). The rate in
vaccinating states declined 88% to 2.5 per 100,000 compared with 53% elsewhere
(to 2.7/100 000). In 2003, cases from vaccinating states accounted for 33% of the
national total vs 65% during the baseline period. Declines were greater among
children aged 2 to 18 years (87%) than among persons older than age 18 years
(69%); the proportion of cases in children dropped from 35% to 19%. Since 2001,
rates in adults have been higher than among children, with the highest rates now 
among men aged 25 through 39 years. CONCLUSIONS: Following implementation of
routine hepatitis A vaccination of children, hepatitis A rates have declined to
historic lows, accompanied by substantial changes in the epidemiologic profile.
Greater decreases in the age groups and regions where routine vaccination of
children is recommended likely reflect the results of implementation of this
novel vaccination strategy. Continued monitoring is needed to verify that
implementation continues to proceed and that low rates are sustained.

Publication Types: 
    Research Support, U.S. Gov't, P.H.S.

PMID: 16014593 [PubMed - indexed for MEDLINE]

324: BMC Infect Dis. 2005 Jul 7;5:56.

Seroprevalence of hepatitis A infection in a low endemicity country: a systematic
review.

Pham B, Duval B, De Serres G, Gilca V, Tricco AC, Ochnio J, Scheifele DW.

BioMedical Data Sciences, GlaxoSmithKline, Ontario, Canada. ba.z.pham@gsk.com

BACKGROUND: In Canada--a low endemicity country, vaccines for hepatitis A virus
(HAV) are currently recommended to individuals at increased risk for infection or
its complications. Applying these recommendations is difficult because the
epidemiology of HAV infection is poorly defined, complex, and changing. This
systematic review aimed to 1) estimate age-specific prevalence of HAV antibody in
Canada and 2) evaluate infection-associated risk factors. METHODS: MEDLINE
(1966-2005) and EMBASE (1980-2005) were searched to identify relevant studies for
the systematic review. Archives for the Canada Diseases Weekly Report (1975-1991)
and Canada Communicable Disease Report (1992-2005) were searched for relevant
public health reports. Data were abstracted for study and participants'
characteristics, age-specific prevalence, and risk factors. RESULTS: A total of
36 reports describing 34 unique studies were included.The seroprevalence in
Canadian-born children was approximately 1% in ages 8-13, 1-6% in 20-24, 10% in
25-29, 17% in 30-39, and increased subsequently. In age groups below 20 and
20-29, age-specific seroprevalence generally remained constant for studies
conducted across geographic areas and over time.Compared to Canadian-born
individuals, subjects born outside Canada were approximately 6 times more likely 
to be seropositive (relative risk: 5.7 [95% CI 3.6, 9.0]). Travel to high risk
areas in individuals aged 20-39 was associated with a significant increase in
anti-HAV seropositivity (RR 2.8 [1.4, 5.5]). Compared to heterosexuals, men
having sex with men were only at a marginally higher risk (adjusted odds ratio
2.4 [0.9, 6.1]). High risk for seropositivity was also observed for Canadian
First Nations and Inuit populations. CONCLUSION: Results from the current
systematic review show that in this low endemicity country, disease acquisition
occurs in adulthood rather than childhood. The burden of disease is high;
approximately 1 in 10 Canadians had been infected by ages 24-29. The increase in 
prevalence in young adults coincides with disease importation and increasing
frequency of risk factors, most likely behavioral-related ones.Gaps in
seroprevalence data were identified rendering the application of current
immunization recommendations difficult. A nationwide prevalence survey for all
Canadians is needed. This is essential to quantify the effectiveness of current
recommendations and conduct cost-effectiveness evaluations of alternative
immunization programs, if necessary.

Publication Types: 
    Review

PMID: 16001978 [PubMed - indexed for MEDLINE]

325: Pediatr Infect Dis J. 2005 Jul;24(7):652-3.

Hepatitis A virus infection presenting with seizures.

Cam S, Ertem D, Koroglu OA, Pehlivanoglu E.

Division of Pediatric Gastroenterology, Hepatology and Nutrition, Marmara
University School of Medicine, Istanbul, Turkey.

Hepatitis A infection rarely causes extrahepatic manifestations. Here we present 
a 5-year-old patient with an initial complaint of nuchal rigidity and convulsions
during the course of hepatitis A infection. Because hepatitis A virus RNA was
demonstrated in the cerebrospinal fluid, it was thought that convulsions might be
related to this viral infection.

Publication Types: 
    Case Reports

PMID: 15999014 [PubMed - indexed for MEDLINE]

326: Transfusion. 2005 Jul;45(7):1097-105.

Occurrence of hepatitis A virus genotype III in Germany requires the adaptation
of commercially available diagnostic test systems.

Heitmann A, Laue T, Schottstedt V, Dotzauer A, Pichl L.

artus GmbH, Hamburg, Germany. heitmann@artus-biotech.de

BACKGROUND: A blood donation, obtained in 2003 in Germany during the
preseroconversion diagnostic window period of a hepatitis A virus (HAV)
infection, tested HAV-negative by commercially available HAV reverse
transcription-polymerase chain reaction (RT-PCR) detection assays. STUDY DESIGN
AND METHODS: The virus responsible for this infection was identified as HAV
genotype IIIA by characterization of the nearly complete genome sequence.
RESULTS: Thereby, this HAV variant, which was named strain HMH, was detected in
Germany for the first time. Because the commercially available HAV RNA detection 
systems failed to detect this genotype, a real-time RT-PCR kit was developed that
allows quantification and detection of all HAV genotypes. The first nearly
full-length nucleotide sequence so far available for HAV genotype IIIA is also
provided. CONCLUSION: This case demonstrates that owing to the genetic
variability of HAV, constant monitoring and adaptation of the diagnostic nucleic 
acid assays are required to guarantee the safety of blood and blood products.

PMID: 15987353 [PubMed - indexed for MEDLINE]

327: J Microbiol Immunol Infect. 2005 Jun;38(3):176-82.

A seroepidemiologic study of Helicobacter pylori and hepatitis A virus infection 
in primary school students in Taipei.

Lin HY, Chuang CK, Lee HC, Chiu NC, Lin SP, Yeung CY.

Department of Pediatrics, Mackay Memorial Hospital, Taipei, Taiwan.

Helicobacter pylori and hepatitis A virus (HAV) share a common fecal-oral
transmission route. The aim of this study was to investigate the prevalence of
and risk factors for H. pylori and HAV infection in primary school students in
Taiwan. We studied 289 Grade 1 to 6 students from a single primary school in
Taipei County in 2003. The students volunteered for blood tests for H. pylori
immunoglobulin G (IgG) antibody and anti-hepatitis A antibody after consent from 
their parents. Questionnaires were administered to the parents to investigate
possible risk factors. The seroprevalence rates of H. pylori IgG antibody and
anti-hepatitis A antibody were 21.5% (62/289) and 1.4% (4/289), respectively. No 
statistically significant relationship was found between seropositivity for H.
pylori and for HAV. If parents had knowledge of H. pylori and HAV, their children
were significantly more likely to be seronegative for H. pylori (p=0.020, odds
ratio [OR] 2.1, 95% confidence interval [CI] 1.2-3.7) and HAV (p=0.012, OR 11.2, 
95% CI 1.5-83.4). Students whose family members had no history of HAV infection
were significantly less likely to be seropositive for HAV (p=0.001, OR 0.04, 95% 
CI 0.004-0.5). No other factors were found to be significantly associated with
seropositivity, including blood type; age; gender; family members' history of H. 
pylori infection; travel to China; parents' educational level; sources of water
supply; family members' use of tobacco, alcohol, or betel nut; family members'
history of peptic ulcer or gastritis; and students' history of recurrent
abdominal pain. Lack of public health knowledge appears to be related to
seroprevalence of H. pylori in primary school students. The low seroprevalence of
anti-HAV antibodies demonstrates the lack of protection against this infection in
school-age children in Taiwan and suggests that universal administration of HAV
vaccine would be wise.

PMID: 15986067 [PubMed - indexed for MEDLINE]

328: Gastroenterol Clin Biol. 2005 May;29(5):573-6.

Usefulness of specific IgG avidity for diagnosis of hepatitis A infection.

Desbois D, Grangeot-Keros L, Roquebert B, Roque-Afonso AM, Mackiewicz V, Poveda
JD, Dussaix E.

Centre National de Référence pour les virus à transmission entérique, Laboratoire
de Virologie, Hôpital Paul Brousse, Villejuif.

AIM: Diagnosis of acute hepatitis A virus (HAV) infection is classically based on
the detection of HAV-IgM. Nevertheless, HAV-IgM can be positive for patients with
polyclonal stimulation of their immune system (i.e. immune reactivation). To
improve the diagnostic yield, an avidity test for HAV-IgG antibodies was
developed and tested. METHODS: Avidity tests were performed in 128 sera: 11
selected samples from patients with past infection, 15 acute hepatitis A, 10
vaccinated subjects and 4 patients with immune reactivation as well as 84 HAV-IgM
positive unselected sera, provided by routine laboratories. RESULTS: Patients
with past infection had avidities over 70%, whereas avidities in patients with
acute hepatitis A were below 50% during the first month following the onset of
symptoms. As expected, patients with immune reactivation had avidities over 70%
consistent with past infection. The results obtained for the 84 unselected sera
allowed reconsidering the diagnosis of acute hepatitis A for nearly a third of
patients. CONCLUSION: This test could improve the diagnosis of acute hepatitis A 
infection, particularly in elderly patients.

Publication Types: 
    Evaluation Studies

PMID: 15980754 [PubMed - indexed for MEDLINE]

329: J Subst Abuse Treat. 2005 Jul;29(1):47-53.

Knowledge of hepatitis among active drug injectors at a syringe exchange program.

Carey J, Perlman DC, Friedmann P, Kaplan WM, Nugent A, Deutscher M, Masson CL,
Des Jarlais DC.

Department of Medicine, Beth Israel Medical Center, New York, NY 10003, USA.
jcarey@bethisraelny.org

Injecting drug users (IDUs) are at high risk for contracting and spreading viral 
hepatitis through nonsterile injection practices, unprotected sexual contact, and
unsanitary living conditions. We sought to characterize hepatitis knowledge,
prior testing, and vaccination history among IDUs at a New York City syringe
exchange program (SEP). IDU subjects generally had a poor understanding of viral 
hepatitis transmission and prevention. We also found low vaccination rates: only 
8% reported receiving hepatitis A vaccine and 11%, hepatitis B vaccine. Educating
IDUs about risky behaviors and medical preventive interventions, such as vaccines
for hepatitis A and B and treatment for hepatitis C, may help prevent disease and
reduce transmission. Stronger linkages between health-care centers and SEPs, drug
treatment programs, and other service delivery centers where IDUs are encountered
may promote hepatitis education and vaccination.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, U.S. Gov't, P.H.S.

PMID: 15979531 [PubMed - indexed for MEDLINE]

330: World J Gastroenterol. 2005 Jun 28;11(24):3791-3.

Prolonged acute hepatitis A mimicking autoimmune hepatitis.

Mikata R, Yokosuka O, Imazeki F, Fukai K, Kanda T, Saisho H.

Department of Medicine and Clinical Oncology, Graduate School of Medicine, Chiba 
University, Chiba 260-8670, Japan.

AIM: We report a case with a prolonged course of hepatitis A, with alanine
aminotransferase (ALT) higher than 500 IU/L for more than 2 mo. METHODS: A
middle-aged woman had an elevated IgG level of more than 2,000 mg/dL, positive
anti-nuclear antibodies (ANA) and anti-smooth muscle antibodies (ASMA), but no
evidence of persistent hepatitis A virus (HAV) infection. Liver biopsy findings
were compatible with prolonged acute hepatitis, although acute onset of
autoimmune hepatitis could not be ruled out. RESULTS: It was assumed that she
developed a course of hepatitis similar to autoimmune hepatitis triggered by HAV 
infection. Ursodeoxycholic acid (UDCA) treatment was initiated and a favorable
outcome was obtained. CONCLUSION: We describe a case of a middle-aged woman who
showed a prolonged course of acute hepatitis A mimicking autoimmune hepatitis.
Treatment with UDCA proved to be effective.

Publication Types: 
    Case Reports

PMID: 15968741 [PubMed - indexed for MEDLINE]

331: Vaccine. 2005 Jul 14;23(32):4110-9. Epub 2005 Apr 12.

Cost-effectiveness of universal childhood hepatitis A vaccination in Chile.

Valenzuela MT, Jacobs RJ, Arteaga O, Navarrete MS, Meyerhoff AS, Innis BL.

School of Public Health, Faculty of Medicine, University of Chile, Santiago,
Chile.

Hepatitis A is an important public health problem in Chile. Childhood vaccination
has reduced hepatitis A rates in several countries, prompting this evaluation of 
its cost-effectiveness in Chile. Using a Markov model, we project mass
vaccination would reduce hepatitis A cases among birth cohort members and their
personal contacts >80%. Vaccination costs of US dollars 5.3-6.4 million would be 
offset by US dollars 9.2-9.4 million reductions in disease costs. Further,
approximately 70 fatal infections would be averted and >4600 quality-adjusted
life years would be saved. This analysis supports the cost-effectiveness of
universal childhood hepatitis A vaccination in Chile.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15964479 [PubMed - indexed for MEDLINE]

332: Pediatr Infect Dis J. 2005 Jun;24(6):514-9.

Nationwide canadian study of hepatitis a antibody prevalence among children eight
to thirteen years old.

Duval B, De Serres G, Ochnio J, Scheifele D, Gîlca V.

Institut National de Santé Publique du Québec, Canada.
bernard.duval@ssss.gouv.qc.ca

BACKGROUND: Hepatitis A vaccines provide consistent, long-lasting protection and 
have been available for almost 10 years in Canada, but their use remains limited.
It is difficult to assess their optimal utilization given that our knowledge of
hepatitis A epidemiology in Canada is fragmentary. Unlike the United States, no
nationwide study of hepatitis A prevalence has ever been done in Canada.
Consequently we do not know the incidence of infection in children and what would
be the most appropriate age for hepatitis A vaccination. OBJECTIVE: To estimate
the proportion of 8- to 13-year-old children who have been infected with
hepatitis A virus (HAV) and the risk factors for this infection on a nationwide
scale. METHODS: Children were sampled in 10 Canadian provinces, comprising 5
regions, using random digit dialing methodology with regional stratification.
Demographic data and information about risk factors for hepatitis A were
collected by the telephone interviewers. Oral fluid samples were self-collected
and mailed to the laboratory, where they were tested for anti-HAV IgG. RESULTS:
Of 6740 contacted families with a child of required age, 1688 (25%) agreed to
participate and answered the questionnaire. From these, 1074 oral fluid samples
were received, and 1057 could be analyzed. Anti-HAV IgG was detected in 2.7% of
subjects, with variation by region from 0.8 to 3.4%. The parents of 54 subjects
(5.1%) reported that their child had previously been vaccinated against HAV.
Anti-HAV IgG was present in 2.0% of unvaccinated subjects, among whom antibody
prevalence was 19.4% in children born in HAV-endemic countries, 6.1% in Native
children and 4.2% in travelers to endemic countries. In multivariate analysis of 
all subjects, the presence of anti-HAV IgG was significantly associated with
birth in an endemic country, travel to an endemic country, Native status
(American Indian and Inuit population), female gender and vaccination against
HAV. In nonvaccinated, non-Native children born in Canada who did not travel to
endemic countries, anti-HAV prevalence was 1.1%. CONCLUSIONS: The risk for
hepatitis A during childhood is low in Canada. Almost all teenagers (>97%) would 
be at risk for infection in case of contact with HAV. Changes in immunization
policy against hepatitis A should be considered.

PMID: 15933561 [PubMed - indexed for MEDLINE]

333: Appl Environ Microbiol. 2005 Jun;71(6):3359-63.

Development and evaluation of a broadly reactive TaqMan assay for rapid detection
of hepatitis A virus.

Jothikumar N, Cromeans TL, Sobsey MD, Robertson BH.

Department of Environmental Sciences and Engineering, University of North
Carolina at Chapel Hill, 27599-7431, USA. JIN2@cdc.gov

Primers and a TaqMan probe for the 5'-untranslated region (UTR) of the hepatitis 
A virus (HAV) genome were designed and evaluated. The assay detected 0.5
infectious units of HAV and 40 copies of a synthetic transcript and provides an
important screening tool for rapid quantitative HAV detection in clinical or
environmental samples.

Publication Types: 
    Evaluation Studies
    Research Support, Non-U.S. Gov't

PMID: 15933042 [PubMed - indexed for MEDLINE]

334: Southeast Asian J Trop Med Public Health. 2004 Dec;35(4):959-61.

Prevalence of hepatitis A virus infection in children with biliary atresia.

Chongsrisawat V, Theamboonlers A, Poovorawan Y.

Center of Excellence in Viral Hepatitis, Department of Pediatrics, Faculty of
Medicine, Chulalongkorn University, Bangkok, Thailand.

This study aimed at identifying the prevalence of hepatitis A virus (HAV)
infection in children with biliary atresia (BA). Blood samples were collected
from children with BA whom had undergone portoenterostomy and attended the
pediatric liver clinic, King Chulalongkorn Memorial Hospital between May 2002 and
May 2003. Seventy-seven patients, 45 females and 32 males, ages ranging from
0.2-19 years (mean +/- SD = 5.9 +/- 4.6 years) were enrolled in the study. The
HAV seropositivity rate of patients aged <10 years and > or =10 years were 13.1% 
and 25%, respectively. The seropositivity rate of patients with favorable
outcomes (total bilirubin level < or =2 mg/dl) and unfavorable outcome (total
bilirubin level >2 mg/dl) were 17.5% and 13.5%, respectively, which were not
statistically different (p = 0.6). Children suffering from BA with failed
portoenterostomy are at risk of developing severe liver damage at an early age.
In these patients a superimposed acute liver infection due to a hepatitis virus, 
including HAV, may affect liver function and lead to particularly severe disease.
The effectiveness of HAV immunization in this particular group of children merits
further study.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15916098 [PubMed - indexed for MEDLINE]

335: Southeast Asian J Trop Med Public Health. 2004 Dec;35(4):954-8.

Immunizing children to protect against the increasing risk of hepatitis A in
adolescents and young adults in South Korea.

Sohn YM, Lee JS, Park JH, Poerschke G, Eves K, Gress J, Kuter B.

Department of Pediatrics, Yongdong Severance Hospital, Yonsei University College 
of Medicine, Seoul, Korea. ymsohn@navekids.co.kr

We evaluated the CR326F strain (VAQTA) derived hepatitis A vaccine in Korean
children and adolescents >2 years of age to consider a future immunization
program. In our study, the pediatric two-dose regimen of VAQTA was found to be
generally well tolerated and resulted in 100% (95% CI 94.8, 100.0) seroconversion
after 2 doses. Immunizing children with the HAV vaccine routinely should be
considered in South Korea, particularly in areas where recent outbreaks have
occurred.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15916097 [PubMed - indexed for MEDLINE]

336: Southeast Asian J Trop Med Public Health. 2004 Dec;35(4):949-53.

Field performance of VAQTA (inactivated, purified hepatitis a vaccine) in Chinese
children in Jiangsu.

Wang H, Chen X, Chen Z, Lu W, Poerschke G, Eves K, Gress J, Kuter B.

Jiangsu Center of Disease Control, Jiangsu, China.

In Jiangsu, 30% of children between the ages of 5 and 8 years test seropositive
for hepatitis A. The safety, tolerability, and immunogenicity of a 2-dose regimen
(0, 6 months) of VAQTA (0.5 ml of 25U) administered IM in 50 healthy children
aged 5 to 8 years without prior serological screening was evaluated. Blood
samples were collected prior to the first dose and after each additional dose of 
VAQTA to determine the initial anti-HAV serostatus and response rates to the
vaccine. Twelve children (24%) were initially seropositive and 38 (76%) were
initially seronegative. Four weeks after the primary dose of VAQTA, 34 of the 38 
subjects (89.5%, 95% CI 75 to 97) were anti-HAV seropositive. The geometric mean 
titer was 33.1 mIU/ml (95% CI 22.4 to 49.0). After the booster dose at 6 months, 
all the subjects were seropositive (37/37), giving a seroconversion of 100% (95% 
CI: 90, 100). The geometric mean titer was 7585.8 mIU/ml (95% CI: 5623.4 to
10,471.3). Adverse experiences were generally mild and transient. Results of this
study are consistent with results from a previous double-blind randomized trial
of this vaccine and confirm that VAQTA is highly immunogenic, and generally
well-tolerated.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15916096 [PubMed - indexed for MEDLINE]

337: Trop Gastroenterol. 2004 Oct-Dec;25(4):162-3.

Is vaccination against hepatitis A virus required in patients with cirrhosis of
the liver?

Duseja A, Sharma S, Das K, Dhiman RK, Chawla YK.

Department of Hepatology, Postgraduate Institute of Medical Education and
Research, Chandigarh.

Hepatitis A virus (HAV) superinfection can cause decompensation in patients with 
chronic liver disease. The risk of HAV superinfection depends on the endemicity
of HAV in that particular population. Recommendations of vaccination against HAV 
in patients with cirrhosis of the liver in India are lacking. Our aim was to
assess the seroprevalence of anti-HAV antibodies in our population of patients
with cirrhosis of the liver. In a retrospective analysis, the serum of 55
patients with cirrhosis of the liver was tested for total anti-HAV antibodies by 
ELISA. In the 35 patients who presented with acute decompensation, the serum was 
also analysed for IgM anti-HAV antibodies. Fifty-four of the 55 cirrhotics (99%) 
were positive for total anti-HAV antibodies. All 35 patients with decompensated
liver disease were also positive for total anti-HAV antibodies, and none of them 
tested positive for IgM anti-HAV antibodies. Most of the patients with cirrhosis 
of the liver in the population studied were already exposed to HAV. Routine
vaccination against HAV cannot be recommended in these patients.

PMID: 15912973 [PubMed - indexed for MEDLINE]

338: J Assoc Physicians India. 2004 Oct;52:785-7.

Should one vaccinate patients with chronic liver disease for hepatitis A virus in
India?

Anand AC, Nagpal AK, Seth AK, Dhot PS.

Army Hospital R and R and Armed Forces Transfusion Unit, New Delhi-l 10 010.

BACKGROUND: Hepatitis A virus (HAV) vaccination is recommended worldwide for
patients with chronic liver disease to prevent decompensation due to
superinfection with HAV. India being endemic for HAV, the prevalence of
pre-existing antibodies against HAV due to subclinical exposure to the virus in
childhood among patients with chronic liver disease may be high and, therefore,
vaccination may not be needed. However, little data are available on the
prevalence of HAV antibody among patients with chronic liver disease in India.
METHODS: All patients with chronic liver disease seen at Gastroenterology Center,
Army Hospital R and R, New Delhi during the year 2002 and diagnosed to have
either chronic liver disease were tested for the presence of IgG anti-HAV
antibody in their sera (using a commercial ELISA kit). All patients with acute
exacerbation or rapid deterioration of a preexisting chronic liver disease were
separately studied for presence of IgM anti-HAV. In addition, a matched number of
patients who attended the center due to diseases other than liver disease were
also studied as controls. RESULTS: One hundred and eighty seven patients of
chronic liver disease and 89 controls were studied. Mean age of these two groups 
was 38.6 and 42.1 years and 153 (81.8%) and 78 (87.6%) of them were males
respectively. Etiology of chronic liver disease was HBV infection in 91(48.7%),
HCV infection in 62 (33.2%), autoimmune chronic hepatitis in 3 (1.6%), PBC in
seven (3.7%) and cryptogenic 24 (12.8%). Of these 179 (95.7%) patients tested
positive for IgG anti-HAV. A total of 37 hospitalisations in 29 patients were
noted during the study period due to acute exacerbation of pre-existing chronic
liver disease. None of these were positive for IgM anti-HAV, while 28 were
positive for IgG anti-HAV. Among the controls, 87 controls (94.6%) were positive 
IgG anti-HAV. The prevalence of anti-HAV positivity was similar among patients
with various etiologies. CONCLUSION: Vaccination against HAV is not routinely
required among patients with chronic liver disease in India as there is a very
high prevalence of pre-existing antibodies in these patients. HAV superinfection 
as a cause of acute exacerbation of chronic liver disease was not seen in this.

PMID: 15909855 [PubMed - indexed for MEDLINE]

339: Med J Malaysia. 2004 Dec;59(5):670-3.

Hepatitis A outbreak in Hulu Langat District, Selangor State, Malaysia during
April--October 2002.

Venugopalan B, Nik Rubiah NA, Meftahuddin T, Ayu M, Prema R, Ruhaini I, Murugan
S.

Selangor State Health Department, Hulu Langat District Health Office.

A Hepatitis A outbreak occurred in Mukim Hulu Langat, Hulu Langat district from
April 2002 to October 2002. Of the 51 cases notified, most were among students
and the ethnic groups involved were Malays and the Orang Asli (local indigenous
community). Epidemiological investigations revealed that the cases were localized
along rivers used for recreational activities in this area. River water analysis 
indicated human faecal contamination and it was believed that the contamination
was due to the Orang Asli community living upstream. This occurred due to lack of
toilet facilities, water at point of use and the existing traditional practices
of the Orang Asli community. Control measures instituted were intense health
education to the Orang Asli to avoid using the rivers for defecation, multi
agency efforts to provide sanitary toilets and adequate water to the villages
affected. Future measures include conducting a sero- prevalence survey to
determine the feasibility of Hepatitis A immunization to the susceptible
population in this area. The outbreak that began in April 2002 was controlled by 
October 2002.

PMID: 15889571 [PubMed - indexed for MEDLINE]

340: MMWR Morb Mortal Wkly Rep. 2005 May 13;54(18):453-6.

Positive test results for acute hepatitis A virus infection among persons with no
recent history of acute hepatitis--United States, 2002-2004.

Centers for Disease Control and Prevention (CDC).

Hepatitis A is a nationally reportable condition, and the surveillance case
definition includes both clinical criteria and serologic confirmation. State
health departments and CDC have investigated persons with positive serologic
tests for acute hepatitis A virus (HAV) infection (i.e., IgM anti-HAV) whose
illness was not consistent with the clinical criteria of the hepatitis A case
definition. Test results indicating acute HAV infection among persons who do not 
have clinical or epidemiologic features consistent with hepatitis A are a concern
for state and local health departments because of the need to assess whether
contacts need postexposure immunoprophylaxis. This report summarizes results of
three such investigations, which suggested that most of the positive tests did
not represent recent acute HAV infections. To improve the predictive value of a
positive IgM anti-HAV test, clinicians should limit laboratory testing for acute 
HAV infection to persons with clinical findings typical of hepatitis A or to
persons who have been exposed to settings where HAV transmission is suspected.

PMID: 15889006 [PubMed - indexed for MEDLINE]

341: Z Gastroenterol. 2005 May;43(5):451-4.

Acute fatty liver of pregnancy -- an underlying condition for herpes simplex type
2 fulminant hepatitis necessitating liver transplantation.

Luzar B, Ferlan-Marolt V, Poljak M, Sojar V, Stanisavljević D, Bukovac T,
Markovic S.

Institute of Pathology, Medical Faculty, Ljubljana, Slovenia.
bostjan.luzar@mf.uni-lj.si

The infrequent occurrence of herpes simplex virus (HSV) hepatitis in healthy
women in comparison with the high prevalence of HSV infections suggests that, in 
addition to deranged immunity, an underlying condition in the liver might be
necessary to develop HSV hepatitis. We report the case of a 28-year-old pregnant 
woman in the 28 (th) week of gestation. Following HSV type 2 infection of the
uterine cervix, acute liver failure developed, necessitating urgent liver
transplantation. In addition to fulminant HSV type 2 hepatitis, the explanted
liver also showed the histological features of acute fatty liver of pregnancy.
The presented case suggests a possible pathogenetic role of acute fatty liver of 
pregnancy in the development of fulminant HSV hepatitis following recurrent
infection with HSV in healthy pregnant women. We believe that early
histopathological diagnosis, followed by specific antiviral treatment and liver
transplantation in selected patients may improve the clinical outcome of
otherwise almost uniformly fatal HSV hepatitis.

Publication Types: 
    Case Reports

PMID: 15871067 [PubMed - indexed for MEDLINE]

342: Cent Eur J Public Health. 2005 Mar;13(1):20-3.

Safety and immunogenicity of a combined vaccine against hepatitis A and B in
patients with autoimmune hepatitis.

Beran J, Dedek P, Stepánová V, Spliio M, Pozler O.

Department of Infectious Diseases, University Hospital, Hradec Králové, Czech
Republic. jiri.beran@vakcinace.cz

Patients with autoimmune hepatitis (AIH) are a group at risk of disease
exacerbation or relapse of the underlying disease should they fall ill with
infectious hepatitis A (HAV) or B (HBV). Therefore, it seems appropriate to
protect this group of persons against HAV and HBV disease by vaccination. An open
study evaluated the safety, reactogenicity and immunogenicity of a combined HAV
and HBV vaccine in 10 patients with AIH (6 patients aged 1-15 years and four
patients aged 16+ years). The vaccine was administered using a three-dose
vaccination schedule (0, 1 and 6 months). The vaccine course was well tolerated, 
safe and did not aggravate the clinical course of the underlying disease.
Patients responded with 100% seroconversion for antibody to the HAV vaccine
component and geometric mean antibody concentration (GIVIC) comparable to healthy
cohorts. Response to the HBV component antigen was comparable to previous reports
of HBV vaccination in immune compromised individuals with lower GMC than observed
in healthy populations. One month after the third vaccine dose (month 7), all six
vaccinees in the 1-15 years age group developed protective levels of anti-HBs as 
compared to two of the four vaccinees in the 16+ years age group.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15859175 [PubMed - indexed for MEDLINE]

343: Am J Public Health. 2005 May;95(5):900-5.

Hepatitis A--related mortality in California, 1989-2000: analysis of multiple
cause-coded death data.

Wise ME, Sorvillo F.

Department of Epidemiology, UCLA School of Public Health, 90095-1772, USA.
mawise@ladhs.org

OBJECTIVES: We estimated the hepatitis A (HA) mortality rate in California,
assessed demographic differences in HA-related mortality, and examined
comorbidities listed on death certificates in order to provide information for
health policy and planning related to HA vaccination. METHODS: We identified
HA-related deaths in California from 1989 to 2000 with multiple-cause-of-death
files and calculated mortality rates and rate ratios. RESULTS: We identified 402 
HA-related deaths between 1989 and 2000; the annual age-adjusted HA-related
mortality rate was 1.20 deaths per 1 million persons. Older individuals, men,
Latinos, and American Indians/Alaska Natives had elevated mortality rates. Liver 
conditions and non-A viral hepatitis infections were more common among HA-related
deaths than among all other deaths. CONCLUSIONS: Current immunization practices
should be reevaluated and the expansion of current vaccination guidelines for
groups that have elevated HA-related mortality rates should be considered.

PMID: 15855472 [PubMed - indexed for MEDLINE]

344: J Viral Hepat. 2005 May;12(3):315-21.

Determinants of acquiring hepatitis A virus disease in a large Italian region in 
endemic and epidemic periods.

Lopalco PL, Malfait P, Menniti-Ippolito F, Prato R, Germinario C, Chironna M,
Quarto M, Salmaso S.

Sezione di Igiene-Dipartimento di Medicina Interna e Medicina Pubblica,
Università di Bari, 70124 Bari, Italy.

Viral hepatitis A is endemic in Puglia region (southeast Italy). Over the last 13
years, annual incidence rates have ranged from 4 to 138 per 100,000 inhabitants
and periodical regional epidemics have been described. Between 1 January 1996 and
31 December 1997 over 11,000 cases of hepatitis A were reported accounting for an
annual incidence rate over 130/100,000. To identify exposures during the
epidemics, a case-control study was performed in two different rounds and since
1997, an enhanced surveillance system has permitted the monitoring of exposures
of subsequent cases. Raw seafood consumption was identified as the major risk
factor for hepatitis A. Adjusted odds ratio and 95% confidence intervals for this
exposure from the first round of the case-control study was 38.6 (12.2-122.4) and
for the second round for consumption of raw mussels it was 30.7 (16.0-52.0).
Hepatitis A epidemiology in Puglia is consistent with an endemic situation
sustained by locally contaminated seafood consumed raw and by the recurrence of
large epidemics, where size is influenced by the accumulation of susceptible
subjects in the population.

Publication Types: 
    Comparative Study

PMID: 15850473 [PubMed - indexed for MEDLINE]

345: J Med Virol. 2005 Jun;76(2):271-8.

Rapid investigation of hepatitis A virus outbreak by single strand conformation
polymorphism analysis.

Mackiewicz V, Roque-Afonso AM, Marchadier E, Nicand E, Fki-Berrajah L, Dussaix E.

Centre National de Référence du Virus de l'Hépatite A, Laboratoire de Virologie, 
Hôpital Paul Brousse, Assistance Publique-Hôpitaux de Paris, Villejuif, France.
vincent.mackiew@pbr.ap-hop-paris.fr

Investigation of hepatitis A virus (HAV) outbreaks often implies nucleotide
sequence analysis. As an alternative method for the identification of related
strains, single strand conformation polymorphism method (SSCP) was compared to
sequence analysis. Twenty-three strains from sporadic and outbreak cases were
studied retrospectively. SSCP, sequence identity and phylogenetic analyses were
conducted on a 267 bp fragment of the VP1-2A variable region. The results of SSCP
pattern comparison and sequence identity were highly correlated (r = 0.92, P <
0.001). If SSCP showed similar patterns, the VP1-2A fragments had a high and
significant probability to have a sequence identity over 99.6%. Results were
concordant for outbreak strains. The only discordant result concerned a cluster
of three sporadic cases evidenced by phylogenetic analysis while SSCP showed
similar patterns for only two of these three cases. A prospective SSCP analysis
of a recent HAV outbreak confirmed the reliability of this technique. SSCP may
thus provide a rapid and cost-effective tool for preliminary investigation of HAV
outbreaks, before undertaking exhaustive nucleotide sequence analysis. Copyright 
2005 Wiley-Liss, Inc.

Publication Types: 
    Comparative Study

PMID: 15834883 [PubMed - indexed for MEDLINE]

346: Int J Epidemiol. 2005 Jun;34(3):600-9. Epub 2005 Apr 14.

The effects of socioeconomic development on worldwide hepatitis A virus
seroprevalence patterns.

Jacobsen KH, Koopman JS.

Department of Epidemiology, University of Michigan, Ann Arbor MI, USA.
jacobsen@calvin.edu

BACKGROUND: Hepatitis A virus (HAV) infection confers long-term immunity, so
mathematical analysis of age-specific seroprevalence in populations can reveal
changes in the infection rate over time. HAV transmission is related to access to
clean drinking water, personal hygiene and public sanitation. METHODS: We used an
SIR (susceptible-infectious-recovered) compartmental model with age structure to 
fit a time-dependent logistic function for HAV force of infection for 157
published age-seroprevalence data sets. We then fit linear regression models for 
socioeconomic variables and infection rate. RESULTS: The proportion of the
population with access to clean drinking water, the value of the human
development index (HDI), and per capita gross domestic product (GDP) are all
inverse predictors of HAV infection rates. Declining infection rates were
observed in 65.6% of the surveys. Discussion This work demonstrates the utility
of HAV seroprevalence studies to reveal patterns of change in force of infection 
and to assess the association between socioeconomic risk factors and transmission
rates.

PMID: 15831565 [PubMed - indexed for MEDLINE]

347: Asian Pac J Allergy Immunol. 2004 Dec;22(4):237-42.

Changing hepatitis A epidemiology and the need for vaccination in Korea.

Kang JH, Lee KY, Kim CH, Sim D.

Department of Pediatrics, Our Lady of Mercy Hospital, Catholic University of
Korea, Incheon, South Korea.

Hepatitis A is a vaccine-preventable disease with 1.5 million people infected
world-wide annually. Improvement in the socio-economic status and general public 
health measures of Asian countries over the last 20 years has led to a shift in
the seroprevalence of hepatitis A in many of these countries. In Korea, like in
many other developed countries, this lowered endemicity has caused an upward
shift in the average age of infection, resulting in larger numbers of individuals
at risk of clinically significant hepatitis A infection. Sporadic outbreaks
increase the public health burden of the disease. Inactivated hepatitis A
vaccines are an effective prevention measure and have been shown to be safe,
efficacious and well-tolerated in Korean children. Given this changing
epidemiology of the disease and the associated increase in morbidity, vaccination
of young children who are not immune, as well as other high risk groups, should
be recommended.

Publication Types: 
    Review

PMID: 15783137 [PubMed - indexed for MEDLINE]

348: Vaccine. 2005 Apr 22;23(22):2876-80.

A two-dose schedule for combined hepatitis A and B vaccination in children aged
6-15 years.

Kurugöl Z, Mutlubaş F, Ozacar T.

Department of Paediatrics, Ege University Faculty of Medicine, Izmir, Turkey.
kurugol@med.ege.edu.tr

A combined hepatitis A and B vaccine, Twinrix, in a paediatric formulation for
ages 1-15 years and in an adult formulation for those ages 16 years and older,
became commercially available in Turkey as well as in many countries. It is
administered according to a three-dose schedule (0, 1 and 6 months). A reduction 
in the number of doses would improve the compliance rate and reduce
administration costs. Therefore, we planned a trial evaluation of the
immunogenicity, safety and reactogenicity profile of a high-dose combined
hepatitis A and B vaccine, administered in two doses, compared with the profile
of a paediatric-dose combined vaccine, administered in three doses, in healthy
children aged 6-15 years. One hundred children were randomly attributed to the
two study groups. The first group (paediatric-dose vaccine group) received the
licensed Twinrix Paediatric, at months 0, 1 and 6; the second group (high-dose
vaccine group) received the high-dose vaccine, following a 0, 6 months schedule. 
The reactogenicity was assessed after each vaccine dose. The immunogenicity was
evaluated by testing for anti-HBs and anti-HAV antibodies. Seroconversion rates
and geometric mean titres (GMTs) were compared. Both formulations of the combined
vaccine were well tolerated. The high-dose combined vaccine administered in two
doses, elicits satisfactory immunogenicity profiles, similar to those elicited by
the paediatric vaccine administered in three doses. On completion of the
vaccination schedule in the two groups all children were protected against
hepatitis B and immune for hepatitis A. Anti-HAV GMTs after completion of the
vaccination schedule were 7163 mlU/ml in the paediatric-dose group, 8241 mlU/ml
in the high-dose group; anti-HBs GMTs were 8679 and 4583 mlU/ml, respectively.
These results indicate that a two-dose schedule, compared with the standard
three-dose schedule, offers fewer injections for satisfactory protection against 
the two infections. This means fewer clinic visits, lower administration costs,
better compliance, and higher coverage rate. Therefore, this two-dose schedule
can be considered an appropriate regimen for the immunization of children and
adolescents against hepatitis A and B infection, in the context of school-based
immunization programmes.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial

PMID: 15780736 [PubMed - indexed for MEDLINE]

349: Commun Dis Public Health. 2004 Dec;7(4):289-93.

Hepatitis A vaccination--a prison-based solution for a community-based outbreak?

Gilbert RL, O'Connor T, Mathew S, Allen K, Piper M, Gill ON.

Prison Surveillance Unit, Communicable Disease Surveillance Centre, Health
Protection Agency Centre for Infections, 61 Colindale Avenue, London NW9 5EQ.
ruth.gilbert@hpa.org.uk

In December 2001, an increase in cases of hepatitis A was observed in South
Yorkshire. Cases were predominantly young males who reported injecting drug use. 
A community-based vaccination programme was introduced in November 2002, but new 
cases continued to occur. In March 2003, a vaccination campaign was implemented
in the local prison for a four-week period. One thousand two hundred and
thirty-six (91%) prisoners were vaccinated. Two thirds (895/1,363) of the
prisoners came from the area affected by the outbreak and 52% (465/895) reported 
injecting drugs. The median age of injectors was 25 years. Notifications of cases
of hepatitis A from South Yorkshire ceased in August 2003. Although on this
occasion the prison vaccination campaign was probably implemented too late to
have had a significant impact on the local outbreak, a large number of young male
injectors from the local area were successfully vaccinated. This suggests that a 
prison-based intervention offers a potentially effective way of immunising the
IDU population and interrupting a community-based outbreak.

Publication Types: 
    Clinical Trial

PMID: 15779792 [PubMed - indexed for MEDLINE]

350: Scand J Infect Dis. 2005;37(2):127-30.

Hepatitis A infection and vaccination among Danish blood donors.

Christensen PB, Homburg KM, Sørensen LT, Georgsen J.

Department C of Medicine, Section of Infectious Diseases, Odense University
Hospital, Odense, Denmark. peer.christensen@dadlnet.dk

When testing 466 Danish blood donors, of whom 60 reported to be vaccinated
against hepatitis A, 55 (11.8%, 95% CI: 9.0-15.1) had detectable levels of
anti-hepatitis A virus IgG (> 10 m IU/ml). Among unvaccinated donors, the
prevalence rate was 23/376 (6.1%, 95% CI: 3.9-9.0) with age above 50 y and use of
private water supply being independently associated with seropositivity.

PMID: 15773034 [PubMed - indexed for MEDLINE]

351: Gastroenterol Hepatol. 2005 Mar;28(3):118-25.

Epidemiology of hepatitis A and E virus infection in Brazil.

Carrilho FJ, Mendes Clemente C, Silva LC.

Department of Gastroenterology, University of São Paulo School of Medicine, São
Paulo, Brazil. fjcarril@usp.br

This review has the objective to discuss the epidemiological aspects of the
enterically transmitted hepatitis A and E in Brazil. The prevalence of hepatitis 
A varies greatly in different Brazilian regions, from 56% in South and Southeast 
to 93% in North region (Manaus, Amazon). Such differences are also found in
different socioeconomic levels among age groups. A significantly higher
prevalence was seen in the low socioeconomic group between 1-30 years. This
difference is most striking in the first 10 years of age (23.5% vs 60.0%,
high/middle vs low, respectively). Despite the improvements in sanitary
conditions, hepatitis A is still endemic and outbreaks may occur. As an
increasing proportion of the population is becoming susceptible to hepatitis A
virus infection and as adult individuals may present more severe forms of the
disease, the authors conclude that the implement of hepatitis A vaccination
should be considered. Some Brazilian data have shown that the genotype found in
our country were IA and IB. Isolates from this study were closely related
genetically (or even identical) to isolates originating in other South American
countries and overseas, providing firm evidence for epidemiological links between
persons who travel to endemic areas. In spite of favorable environmental
conditions, outbreaks of hepatitis E have never been reported in Brazil.
Nevertheless, reports have demonstrated the evidence of anti-hepatitis E virus
antibodies in some Brazilian regions. The seroprevalence of IgG anti-hepatitis E 
virus among normal populations shows positivities of 6.1% in gold-miners, 3.3% in
general population, 2.0-7.5% in blood donors, 1.0% in pregnant women, and 4.5% in
children, with no differences among regions. In populations at risk the
prevalence of anti-hepatits E virus varies greatly. Among patients with acute
non-A, non-B, non-C hepatitis 2.1% was detected in the Southeast to 29% in the
Northeast, in 10.6% of acute non-A, non-B, non-C hepatitis relatives in the
Amazon basin, in 12% of acute sporadic non-A non-B hepatitis patients in the
Northeast, a co-infection with acute hepatitis A in 25 to 38% in the Northeast,
in 14 to 18% among prostitutes and women considered at risk for human
immunodeficiency virus in the Southeast, and in 12% of the intravenous drug users
in the Southeast.

Publication Types: 
    Review

PMID: 15771857 [PubMed - indexed for MEDLINE]

352: Rheumatol Int. 2005 Aug;25(6):475-7. Epub 2005 Mar 12.

Spontaneous renal laceration as the presenting feature of polyarteritis nodosa in
a patient with familial Mediterranean fever after hepatitis A infection.

Candan F, Ayan S, Tas F, Gökce G, Elagoz S.

Department of Internal Medicine, School of Medicine of Cumhuriyet University,
Sivas, Turkey, 58140. fcandan@cumhuriyet.edu.tr

We report a life-threatening spontaneous renal laceration with no history of
bleeding diathesis or any trauma in a patient with FMF after acute hepatitis A
virus (HAV) infection. Right nephrectomy was inevitable and histological
investigation of the removed right kidney revealed a polyarterits nodosa (PAN).
This case underlines the possibility that simultaneous PAN and immunsupressive
treatment besides colchicine should be considered for patients with FMF. Also,
patients with FMF who are not immune may be vaccinated for HAV which could be a
predisposing mechanism for vasculitic hemorrhage.

Publication Types: 
    Case Reports

PMID: 15765217 [PubMed - indexed for MEDLINE]

353: Expert Opin Pharmacother. 2005 Feb;6(2):157-64.

Hepatitis A vaccines: the growing case for universal immunisation of children.

Scheifele DW.

BC Children's Hospital, Vaccine Evaluation Center, University of British
Columbia, Vancouver, British Columbia, Canada. dscheifele@cw.bc.ca

Hepatitis A virus (HAV) infection results in a debilitating, multi-week illness
in older children and adults that can be avoided with pre-exposure immunisation. 
Inactivated HAV vaccines are safe, highly effective and induce long-lasting
protection. Immunisation has typically been recommended only for groups at
highest risk of infection or complications, with variable success. This paper
reviews the outcomes of several new programmes of universal HAV immunisation of
children and/or adolescents. These programmes were associated with substantial
disease rate reductions, extending beyond the immunised individuals and age
groups (herd immunity), and promise additional benefits as immunised cohorts
enter adulthood risk groups. Universal programmes are cost-effective, especially 
when a combined hepatitis A and B vaccine can be used to minimise incremental
costs, and deserve wider consideration in developed countries.

Publication Types: 
    Review

PMID: 15757414 [PubMed - indexed for MEDLINE]

354: Vaccine. 2005 Mar 18;23(17-18):2176-80.

Vaccination against hepatitis A during outbreaks starting in schools: what can we
learn from experiences in central Italy?

Bonanni P, Franzin A, Staderini C, Pitta M, Garofalo G, Cecconi R, Santini MG,
Lai P, Innocenti B.

Public Health Department, University of Florence, Viale G.B. Morgagni 48-50134
Florence, Italy. paolo.bonanni@unifi.it

Two outbreaks of hepatitis A started almost simultaneously in a maternal school
and in a day care centre located at opposite sides of Florence, Italy, at the end
of 2002. Both of them originated from immigrant children, and in both cases,
hepatitis A was initially not recognised due to aspecific symptoms. While
vaccination of contacts started with delay in the first outbreak, the same
intervention was organised and performed in 3 days in the other. The outbreak
starting in the maternal school caused 30 notified cases, plus 7 cases diagnosed 
retrospectively. Nine of them were in a secondary school, where vaccination (in
accordance with the Italian national guidelines on hepatitis A (HA) vaccination) 
had been started only after a secondary case occurred. Only three cases occurred 
overall in the other outbreak starting in the day care centre, where >80% of
infants, children and personnel were immunised. Although few asymptomatic
infections probably occurred, no source of contagion existed any longer 2 months 
after immunisation. A rapid vaccination of school and family contacts of
hepatitis A cases after the first case (irrespective of school grade) seems to
play an important role to shorten outbreak duration.

PMID: 15755590 [PubMed - indexed for MEDLINE]

355: Commun Dis Intell. 2004;28(4):521-7.

A multi-jurisdictional outbreak of hepatitis A related to a youth
camp--implications for catering operations and mass gatherings.

Munnoch SA, Ashbolt RH, Coleman DJ, Walton N, Beers-Deeble MY, Taylor R.

Public and Environmental Health Service, Department of Health and Human Services,
Tasmania. Sally.Munnoch@hunter.health.nsw.gov.au

In June 2003, Australian state and territory health departments were notified of 
an outbreak of Hepatitis A in people who had attended a five-day youth camp.
Approximately 350 people attended the event in Central Australia between 24 and
28 April 2003. The public health investigation comprised of case identification, 
food handler interviews, an environmental health investigation of the campground 
and associated food premises, laboratory analysis of blood specimens and
food/water samples, and an epidemiological study. Twenty-one cases fitted the
case definition for the outbreak. A retrospective cohort study involving four
states was conducted, with 213 people interviewed. Coleslaw and cordial were
significantly associated with illness, however when the two exposures were
adjusted for each other to account for confounding, only coleslaw remained
significantly associated with illness (adjusted RR 2.5, 95% CI 1.09 - 5.77). The 
investigation highlighted a number of food hygiene and safety issues relating to 
the catering of mass gatherings. Implementation of food safety programs in these 
settings are likely to reduce the occurrence of such outbreaks. The recent
proposal by Food Standards Australia New Zealand to mandate food safety programs 
for catering operations is supported.

Publication Types: 
    Comparative Study

PMID: 15745403 [PubMed - indexed for MEDLINE]

356: J Infect Dis. 2005 Mar 15;191(6):957-63. Epub 2005 Feb 11.

Hepatitis a molecular epidemiology in the United States, 1996-1997: sources of
infection and implications of vaccination policy.

Nainan OV, Armstrong GL, Han XH, Williams I, Bell BP, Margolis HS.

Division of Viral Hepatitis, National Center for Infectious Diseases, Centers for
Disease Control and Prevention, Atlanta, Georgia 30033, USA. ovn1@cdc.gov

BACKGROUND: The genetic relatedness of hepatitis A virus (HAV) isolates was
determined to identify possible infection sources for case patients in the
Sentinel Counties Study of Acute Viral Hepatitis. METHODS: A 315-nucleotide
segment of the VP1-P2 region of the HAV genome was amplified and sequenced from
serum of case patients and analyzed together with risk-factor data. RESULTS: Of
508 HAV-RNA-positive case patients, 449 (88.4%) were interviewed, and 255 (50.1%)
reported >/=1 risk factor. Some 123 unique nucleotide sequence patterns (UNSPs)
were identified--77 (62.6%) from only 1 case patient and the rest in 2-99
persons. Among international travelers, a single person was more often infected
with a single type of UNSP (17/54 [31.5%]), compared with other case patients
(48/393 [12.2%]; P<.001). UNSPs from travelers to Mexico (33/37 [89.2%])
clustered with those from Hispanic children (47/49 [95.9%]). Of 119 men who had
sex with men, 96 (80.7%) had the same or similar UNSPs, which were also found in 
37 men and 10 women with no identified infection source. CONCLUSION: HAV is often
transmitted within networks of persons with similar risk factors, which may be
the infection source for others in the community.

Publication Types: 
    Research Support, U.S. Gov't, P.H.S.

PMID: 15717272 [PubMed - indexed for MEDLINE]

357: Southeast Asian J Trop Med Public Health. 2004 Jun;35(2):416-20.

Serological survey of viral hepatitis A, B, and C at Thai Central Region and
Bangkok: a population base study.

Ratanasuwan W, Sonji A, Tiengrim S, Techasathit W, Suwanagool S.

Department of Preventive and Social Medicine, Faculty of Medicine at Siriraj
Hospital, Mahidol University, Bangkok, Thailand.

Hepatitis A, B, and C are important viral hepatitis infections in the Thai
population. Hepatitis B vaccination was included in the Thai Expanded Program on 
Immunization (EPI) 10 years ago. In addition, the seroprevalence of hepatitis A
has significantly changed in the last two decades. This study was done to
evaluate current risk groups for hepatitis A and B infections and identify the
magnitude of hepatitis C infection in the general population of Bangkok and six
provinces in the Central Region of Thailand, during the period October 2000 to
January 2002. This study revealed that the prevalence of anti-HAV in people
younger than 25 years was low but very high in people older than 25 years. The
prevalence of anti-HAV was 1.95% in Bangkok and 12.7% in other provinces in
people younger than 25 years (p<0.001) while 90.9% in Bangkok and 88.2% in other 
provinces among people older than 25 years. Therefore, people who are older than 
25 years should have a blood test for anti-HAV before getting a hepatitis A
vaccination. Approximately 80% of people who are not covered by hepatitis B
vaccination from EPI are at risk of hepatitis B infection and its complications. 
This group of people should receive hepatitis B vaccination. For hepatitis C, the
prevalence is lower than 2% across age groups and areas. Therefore, current good 
primary prevention via blood donor screening and health education must be
maintained.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15691148 [PubMed - indexed for MEDLINE]

358: J Clin Gastroenterol. 2005 Feb;39(2):144-51.

Viral hepatitis in minority America.

Rawls RA, Vega KJ.

University of Florida Health Sciences Center at Jacksonville, Jacksonville, FL
32209, USA.

Viral hepatitis continues as an important public health concern in the United
States. Available data indicate that acute and chronic viral hepatitis remains an
important cause of morbidity and mortality in this country despite the
availability of immunization for hepatitis A and B and pharmacologic therapy for 
chronic hepatitis B and C. Minority populations within the United States are
disproportionately affected by acute and chronic viral hepatitis. Many diseases, 
for example, Barrett's esophagus, affect ethnic groups differently. Viral
hepatitis A, B, and C may demonstrate ethnic variation with regard to their
epidemiology, natural history, clinicopatholgic findings, complications, and
treatment outcomes. This report will review the literature regarding these areas 
in hepatitis A, B, and C among the African American, Hispanic American, and
Native American populations of the United States.

Publication Types: 
    Review

PMID: 15681912 [PubMed - indexed for MEDLINE]

359: Clin Microbiol Infect. 2005 Feb;11(2):145-7.

Environmental risk factors for hepatitis A infection in the Zenica-Doboj Canton, 
Bosnia and Herzegovina.

Uzunovic-Kamberovic S, Durmisevic S, Tandir S.

Laboratory for Clinical and Sanitary Microbiology, Contonal Public Health
Institute Zenica, Bosnia and Herzegovina. selma_kamb@yahoo.com

In the Zenica-Doboj Canton, 1106 hepatitis A virus (HAV) infections were reported
during 2000 (an incidence rate of 252/100 000 population), with 996 (90.1%) cases
occurring in nine community-wide outbreaks. Analysis of water supplies showed
that 398 (19.1%) samples contained coliforms, including 202 (50.8%) that were
contaminated with thermotolerant Escherichia coli. Sewage sanitation systems were
absent or substandard in 53 910 (81.8%) rural households. The group most affected
during outbreaks comprised children aged 7-14 years (incidence rate of 598/100
000). The development of health promotion and prevention initiatives in schools, 
combined with rigorous hygiene measures, will be necessary to achieve control of 
the spread of HAV.

PMID: 15679489 [PubMed - indexed for MEDLINE]

360: Pediatr Int. 2004 Dec;46(6):669-72.

Changes in seroprevalence of hepatitis A in children and adolescents in Manisa,
Turkey.

Tosun S, Ertan P, Kasirga E, Atman U.

Department of Infectious Diseases, Morris Schinassi Pediatric Hospital, Manisa,
Turkey. selmatosun2000@yahoo.com

BACKGROUND: Hepatitis A virus (HAV), being an enteric transmitting virus wide
world, occurs mostly in children of developing countries. However, the virus has 
recently been seen in adolescents and young adults worldwide. The aim of the
present study was to evaluate the seroprevalence of the HAV infection in children
and adolescents in Manisa, Turkey, and to verify whether the increased incidence 
of HAV infection in other parts of the world and Turkey generally is also true
for the area of Manisa. METHODS: The authors studied blood samples of 1395
adolescents and children aged between 6 months and 17 years from the Manisa area 
in order to evaluate the existence of anti-HAV antibodies using micro-ELISA test.
RESULTS: Total seropositivity was 44.6% while age related values were as
followed: 6-23 months, 47.8%; 2-6 years, 23.7%; 7-10 years, 43.4%; 11-14 years,
52.4%; and 15-17 years, 76.6%. These results suggest that the seropositivity
increases significantly among children at school age and also increases parallel 
to age. CONCLUSIONS: According to these results, the authors concluded that there
has been a shift of seropositivity from children to adolescents especially in
families with an average or high socio-economical level.

Publication Types: 
    Comparative Study

PMID: 15660865 [PubMed - indexed for MEDLINE]

361: J Viral Hepat. 2005 Jan;12(1):101-5.

Seroepidemiology of hepatitis A in patients with chronic liver disease.

Saab S, Lee C, Shpaner A, Ibrahim AB.

Division of Digestive Diseases, Department of Medicine, University of California 
Los Angeles, Los Angeles, CA, USA. ssaab@mednet.ucla.edu

Hepatitis A virus (HAV) rarely causes fulminant hepatic failure in the general
population. Yet it is a cause of significant morbidity and mortality in patients 
with chronic liver disease (CLD), in whom routine HAV vaccination is recommended.
However, studies of HAV seroprevalence and exposure predictors in populations
with CLD are scarce. We have studied a cohort of 473 patients with various causes
of CLD between July 2000 and June 2002. Patients were stratified on the basis of 
age, gender, ethnicity and aetiology of liver disease. The HAV seroprevalence in 
patients with CLD was compared with that in the general population. We used a
logistic regression analysis to identify independent predictors of HAV exposure. 
Of the 473 patients studied, HAV seroprevalence was available for 454
individuals. HCV, HBV, alcohol, and HCV and alcohol were the causes of CLD in
337, 72, 37 and eight patients, respectively. The overall HAV seroprevalence was 
55% in the studied cohort. The age-stratified HAV prevalence for ages 21-30,
31-40, 41-50, 51-60, 61-70 and greater than 70 years was 44, 51, 44, 63, 65 and
64%, respectively. Hispanic ethnicity, Asian ethnicity, alcohol use and ages of
51-70 years were found to be independent predictive variables of prior exposure
to HAV. HAV infection in patients with CLD causes considerable morbidity and
mortality. We demonstrated that age-stratified seroprevalence of HAV in patients 
with CLD of various aetiologies is significantly higher than that of the general 
population, and identified several independent predictors of HAV prior exposure.

PMID: 15655056 [PubMed - indexed for MEDLINE]

362: J Clin Virol. 2005 Feb;32(2):128-36.

Molecular epidemiology of hepatitis A in Noord-Brabant, The Netherlands.

Tjon GM, Wijkmans CJ, Coutinho RA, Koek AG, van den Hoek JA, Leenders AC,
Schneeberger PM, Bruisten SM.

Municipal Health Service of Amsterdam (Streeklaboratorium voor de
Volksgezondheid), Nieuw Achtergracht 100, 1018 WT Amsterdam, The Netherlands.
gtjon@ggd.amsterdam.nl

BACKGROUND: Previous studies on the molecular epidemiology of hepatitis A virus
(HAV) in Amsterdam, The Netherlands, show that subgenotype 1A is mainly seen
among homosexual men practising anonymous oral-anal sex in saunas and darkrooms, 
while subgenotype 1B is usually detected among children originating from Morocco,
and subgenotype 3A is mostly found among travellers to Pakistan. OBJECTIVE: We
studied the genotype distribution in a more rural area of The Netherlands,
Noord-Brabant, and compared it with Amsterdam. STUDY DESIGN: We collected blood
and feces samples from 34 HAV IgM(+) individuals who were reported from August
2001-March 2003 at the Municipal Health Service (MHS) Heart for Brabant
(Brabant). We also collected feces samples from nine household contacts of whom
the HAV IgM status was not known. HAV RNA was isolated and subsequently amplified
by reverse transcriptase polymerase chain reaction (RT-PCR) at the VP1-P2a and
the VP3-VP1 region, sequenced and analysed. RESULTS AND CONCLUSIONS: In most
cases, relations between risk groups and HAV subgenotypes in Noord-Brabant were
similar to those in Amsterdam. Next to genotypes 1 and 3 we also detected a
genotype 2/7 strain in a Noord-Brabant case. Also, in contrast to the Amsterdam
study, sporadic transmission occurred among various risk groups. Children
involved in a school-related outbreak were infected with strains identical to one
that was previously isolated from a man who has sex with men (MSM). Also, Dutch
patients having no epidemiological link with Turkish or Moroccan children
harboured strains imported from high-endemic countries. Furthermore, we report a 
special case in which HAV may be causally involved in meningitis. The results of 
this study show that the molecular epidemiology of HAV in The Netherlands can be 
more complicated than previously anticipated and that HAV phylogenetic studies
can provide important information for the design of appropriate public health
measures.

PMID: 15653415 [PubMed - indexed for MEDLINE]

363: Dig Liver Dis. 2004 Dec;36(12):834-42.

Effectiveness of immune globulins in preventing infectious hepatitis and
hepatitis A: a systematic review.

Bianco E, De Masi S, Mele A, Jefferson T.

National Health Institute, Rome, Italy. bianco@iss.it

OBJECTIVE: To assess the effectiveness and safety of immune globulins in
preventing infectious hepatitis and hepatitis A. STUDY DESIGN: Systematic review 
with meta-analysis. DATA SOURCES: We searched the Cochrane Library, MEDLINE,
EMBASE, Biological Abstracts and Science Citation Index to December 2002. Vaccine
manufacturers were contacted for additional data. REVIEW METHODS: We included
randomised controlled trials comparing effectiveness of hepatitis A immune
globulins with no intervention or placebo, and carried out a meta-analysis.
RESULTS: We included six studies (two in Russian). Tested immune globulins show
higher effectiveness than placebo or do-nothing against infectious hepatitis both
in primary prevention and in prevention after exposure (effectiveness 83%; RR:
0.17; 95% CI: 0.15-0.19; and effectiveness 69%; RR: 0.31; 95% CI: 0.20-0.47,
respectively). We found considerable heterogeneity among studies, possibly due to
different methodology, background rates of disease and immune globulins dosage
and concentrations. No safety data were reported in the studies. CONCLUSIONS:
Immune globulins are efficacious in preventing infectious hepatitis and hepatitis
A, but included studies do not report data about their safety. Average length of 
passive protection was three months. Given the notable heterogeneity of
performance of immune globulins, short protection conferred and absence of trial 
safety data, the only indications for the use of immune globulins may be in
situations in which inadequate supplies of vaccine are available or when the
eight-day window of opportunity for vaccine use is past.

Publication Types: 
    Meta-Analysis
    Research Support, Non-U.S. Gov't
    Review

PMID: 15646432 [PubMed - indexed for MEDLINE]

364: Epidemiol Infect. 2004 Dec;132(6):1005-22.

Declining hepatitis A seroprevalence: a global review and analysis.

Jacobsen KH, Koopman JS.

Department of Epidemiology, University of Michigan School of Public Health, Ann
Arbor, MI 48109, USA.

Hepatitis A virus (HAV) is spread by faecal-oral contact or ingestion of
contaminated food or water. Lifelong immunity is conferred by infection or
vaccination, so anti-HAV seroprevalence studies can be used to indicate which
populations are susceptible to infection. Seroprevalence rates are highly
correlated with socioeconomic status and access to clean water and sanitation.
Increasing household income, education, water quality and quantity, sanitation,
and hygiene leads to decreases in HAV prevalence. Japan, Australia, New Zealand, 
Canada, the United States, and most European nations have low anti-HAV rates.
Although anti-HAV rates remain high in most Latin American, Asian, and Middle
Eastern nations, average seroprevalence rates are declining. Surveys from Africa 
generally indicate no significant decline in anti-HAV rates. Because the severity
of illness increases with age, populations with a high proportion of susceptible 
adults should consider targeted vaccination programmes.

Publication Types: 
    Review

PMID: 15635957 [PubMed - indexed for MEDLINE]

365: Vaccine. 2005 Jan 11;23(8):1021-8.

Vaccination in the county jail as a strategy to reach high risk adults during a
community-based hepatitis A outbreak among methamphetamine drug users.

Vong S, Fiore AE, Haight DO, Li J, Borgsmiller N, Kuhnert W, Pinero F, Boaz K,
Badsgard T, Mancini C, Nainan OV, Wiersma S, Bell BP.

Division of Viral Hepatitis, National Center for Infectious Diseases, Centers for
Disease Control and Prevention, 1600 Clifton Road, NE, Mailstop D-66, Atlanta, GA
30333, USA. svong@pasteur-kh.org

Illicit drug use (IDU) is an important risk factor for hepatitis A, but
implementing vaccination programs among drug users is difficult. During January
2001-July 2002, 403 hepatitis A cases were reported in Polk County, Florida; 48% 
were drug users and of these, 80% were recently in jail. To assess the county
jail as a potential vaccination venue, we interviewed 280 inmates and conducted a
serologic survey during July--August 2002. Of these, 227 (81%) reported a past
IDU history. Previous HAV infection was found in 33%. In communities with illicit
drug users at risk for hepatitis A and who are frequently jailed, vaccination
programs in jails could be an important component of a community-based strategy
to control hepatitis A outbreaks among illicit drug users.

Publication Types: 
    Comparative Study

PMID: 15620475 [PubMed - indexed for MEDLINE]

366: Vaccine. 2005 Jan 4;23(7):910-4.

Feasibility of vaccination in preventing secondary cases of hepatitis A virus
infection.

Sagliocca L, Bianco E, Amoroso P, Quarto M, Richichi I, Tosti ME, Carannante N,
Chironna M, Chiriacò P, Di Bari G, Lopalco P, Resta F, Santantonio T, Tantimonaco
G, Mele A.

A.O.G. Rummo, Benevento, Italy.

Although the secondary transmission of hepatitis A virus (HAV) infection is
preventable through vaccination, it is not known whether the vaccination of
household contacts is feasible. To this end, we conducted a prospective cohort
study among the household contacts, 40 years of age or less, of all persons
infected with primary HAV infection (index cases) and admitted to eight hospitals
in southern Italy within 7 days of onset. Household contacts were vaccinated, and
serum samples were taken at vaccination and after 14 and 45 days. Secondary cases
were defined as those with IgM seroconversion occurring at least two weeks after 
enrollment. Coprimary cases were those assumed to have had the same exposure as
the index case. Susceptible cases were those who were negative for both IgG and
IgM. A total of 495 household contacts participated (acceptance rate of 65%); 65%
were vaccinated within 4 days of admission of the index case and 95% within 7
days. At enrollment, 196 (39.6%) household contacts were immune (IgG-positive
serum). During follow-up, 19 (3.8%) were IgM-positive: 13 (2.6%) were coprimary
cases and 6 (1.2%; 95% CI: 0.2-3.2) secondary cases (5 identified at 14 days from
vaccination and 1 at 45 days). Of the 241 susceptible cases, 192 (79.7%) had
developed IgG antibodies at 14 days and only 3 (1.2%) did not develop IgG
antibodies at 45 days. The 65% acceptance rate and the finding that 95% of the
participating household contacts were vaccinated within 7 days of the index
case's hospitalization indicate that timely vaccination is indeed feasible. The
necessity of returning for the collection of blood samples probably decreased the
acceptance rate.

Publication Types: 
    Comparative Study
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 15603892 [PubMed - indexed for MEDLINE]

367: Eur J Cardiovasc Prev Rehabil. 2004 Dec;11(6):471-6.

Helicobacter pylori and hepatitis A virus infections and the cardiovascular risk 
profile in patients with diabetes mellitus: results of a population-based study.

Ongey M, Brenner H, Thefeld W, Rothenbacher D.

Department of Epidemiology, German Centre for Research on Ageing, University of
Heidelberg, Heidelberg, Germany.

OBJECTIVE: The objective of this study was to investigate the associations of
sero-positivity for Helicobacter pylori (HP) and hepatitis A virus infection
(HAV) with prevalence of cardiovascular diseases (CVD) and CVD-risk markers in a 
large population-based sample of patients with diabetes mellitus (DM), who are at
high risk of developing CVD. BACKGROUND: Several studies have suggested that
chronic infections are associated with the development of atherosclerosis and
coronary heart diseases (CHD). METHODS: This analysis is based on the German
National Health Interview and Examination Survey which was conducted in 1998. We 
identified all subjects with prevalent DM aged 40-79 years. Helicobacter pylori
and HAV status were measured by serum immunoglobulin G antibodies. Prevalence of 
several CVD events (myocardial infarction, stroke and CHD) was recorded. In
addition, serum levels of total triglycerides, total cholesterol, high-density
lipoprotein cholesterol, low-density lipoprotein cholesterol and lipoprotein (a) 
were measured. RESULTS: Among the 4285 participants of the German Health Survey
aged 40-79 years, we identified 365 patients with DM. Of these, 32.1% had at
least one CVD and there was a clear increase of CVD with age. Sero-prevalence of 
HP or HAV and their combination was not associated with the prevalence of CVD nor
with mean levels of blood lipids after multivariate adjustment for covariates.
CONCLUSION: In this large group of 365 patients with diabetes mellitus no
association of HP and HAV sero-prevalence with presence of CVDs or the level of
serum lipids was established. Therefore it seems unlikely that HP and HAV
sero-prevalence strongly influence CVD progression in patients with diabetes.

PMID: 15580057 [PubMed - indexed for MEDLINE]

368: Allergy. 2005 Jan;60(1):98-103.

Association of hepatitis A virus infection with allergic sensitization in a
population with high prevalence of hepatitis A virus exposure.

Gonzalez-Quintela A, Gude F, Boquete O, Aguilera A, Rey J, Meijide LM,
Fernandez-Merino MC, Vidal C.

Department of Internal Medicine, Complejo Hospitalario Universitario de Santiago,
Santiago, Spain.

BACKGROUND: An inverse association between allergic sensitization and markers of 
exposure to food-borne and orofecal infections (particularly hepatitis A virus,
HAV) has been reported. The prevalence of HAV exposure and allergic sensitization
vary widely in different areas, and vary along with age within a given area. AIM:
To investigate the association between HAV exposure and allergic sensitization in
adults from a mostly rural area of Spain. METHODS: An age-stratified random
sample of 720 subjects was drawn from the population older than 18 years of
A-Estrada, Spain. From 697 eligible subjects, 469 (67.2%, median age 54 years,
range: 18-92) participated in the study. Positive skin prick tests to a panel of 
aeroallergens defined allergic sensitization. Positive serum HAV antibodies
(assayed in 465 subjects) defined HAV exposure. RESULTS: The prevalence of HAV
exposure was 83.6% (95% CI: 80.7-86.5). The prevalence of allergic sensitization 
was lower in subjects with HAV exposure than in patients without it (25.0%vs
40.0%, OR 0.44, 95% CI: 0.25-0.77, P=0.004), but this association became
substantially altered after adjusting for age, which was closely linked to both
allergic sensitization and HAV exposure (adjusted OR 1.15, 95% CI: 0.60-2.19,
P=0.66). CONCLUSIONS: In a population with high prevalence of HAV exposure, no
significant association between HAV exposure and allergic sensitization is
observed after controlling for the confounding effect of age.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15575938 [PubMed - indexed for MEDLINE]

369: Allergy. 2005 Jan;60(1):30-4.

Does atopy protect against enteric infections?

Black PN.

Department of Medicine, University of Auckland, Auckland, New Zealand.

Allergic sensitization to inhaled allergens and foods is common and is linked to 
the development of asthma, allergic rhinitis and eczema. In view of the morbidity
associated with these diseases it is not clear why the genetic predisposition to 
atopy is so common. Children who are atopic are less likely to develop oral
tolerance to ingested foods and as a result are more likely to have
manifestations of food allergy including wheezing, skin rashes and
gastrointestinal symptoms. Oral tolerance also develops to micro-organisms in the
gastrointestinal tract. Children who are atopic may be protected against enteric 
infections in early childhood because they are less likely to be tolerant of
these organisms. This may explain why individuals who are atopic are less likely 
to have evidence of previous infection with hepatitis A and other enteric
organisms although they are just as likely to have been infected with respiratory
pathogens.

Publication Types: 
    Review

PMID: 15575927 [PubMed - indexed for MEDLINE]

370: J Clin Virol. 2005 Jan;32(1):24-8.

Clinical features and molecular characterization of hepatitis A virus outbreak in
a child care center in Thailand.

Poovorawan Y, Theamboonlers A, Chongsrisawat V, Jantaradsamee P, Chutsirimongkol 
S, Tangkijvanich P.

Viral Hepatitis Research Unit, Center of Excellence in Viral Hepatitis, Faculty
of Medicine, Chulalongkorn University, Bangkok 10330, Thailand.
yong.p@chula.ac.th

BACKGROUND: As a result of declining hepatitis A endemicity in Thailand, an
increasing number of children and adolescents have become susceptible to
hepatitis A virus (HAV) infection. OBJECTIVE: The present study was aimed at both
investigating the clinical features and determining molecular characterization of
HAV during an outbreak, which occurred in a childcare center located in a
suburban area of Bangkok between November 2002 and February 2003. Methods: Serum 
samples obtained from all children in the center were tested for anti-HAV IgG and
anti-HAV IgM. Testing for HAV-RNA was performed in sera, saliva and stool samples
by the reverse transcription-polymerase chain reaction (RT-PCR) with primers
located at the VP1-2A region. To further characterize the HAV genotype serum
derived HAV-RNA-positive PCR products were sequenced. RESULTS: Anti-HAV IgG and
anti-HAV IgM were detected in 74 and 70 of 112 children in the center,
respectively. Among those positive for anti-HAV IgM, 65 cases were asymptomatic, 
while five children had acute clinical hepatitis. The ratio between symptomatic
and asymptomatic children was 1:13. Among the asymptomatic cases, 31 (47.7%)
displayed biochemical hepatitis with elevated alanine aminotransferase (ALT)
levels. All the isolates from this outbreak were found to be of subgenotype IA,
which showed a high level of sequence homology with previous Thai isolates.
HAV-RNA could not be detected in saliva, but was found in stool for at least 3
weeks after initial diagnosis of clinical or biochemical hepatitis. CONCLUSION:
Because of the infection's characteristically asymptomatic spread, hepatitis A
poses an increased risk to childcare centers. The presence of a single
sub-genotype indicates that this HAV strain has been predominantly circulating in
Thailand.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15572002 [PubMed - indexed for MEDLINE]

371: Clin Invest Med. 2004 Oct;27(5):259-64.

Hepatitis A seroprevalence and risk factors among day-care educators.

Muecke CJ, Béliveau C, Rahme E, Soto JC, Gyorkos TW.

Department of Epidemiology and Biostatistics, McGill University, Montréal, Que.

BACKGROUND: Day-care centres play a role in the epidemiology of hepatitis A virus
(HAV). Up-to-date documentation on its seroprevalence and potential risk factors 
among day-care educators, who may be at risk for significant HAV morbidity, is
nevertheless lacking. The availability of a hepatitis A vaccine provides an
additional opportunity for prevention in this population. To determine the
seroprevalence of previous HAV infection among day-care educators and to identify
potential risk factors, we undertook a survey. METHODS: Of 167 randomly selected 
centres, 81 centres participated. Directors and educators completed
questionnaires on risk factors. Sera were collected during on-site visits from
October through December 2001. RESULTS: Seroprevalence of previous HAV infection 
in 492 participating educators was 35.6%. Significant risk factors in
multivariate analysis included birth in a high-versus moderate/low-income country
(odds ratio [OR] 20.8; 95% confidence interval [CI] 9.4-46.0); self-reported HAV 
vaccination (OR 6.1, CI 2.9-13.0); travel to endemic areas (OR 2.4, CI 1.3-4.2); 
and age (5-yr OR 1.5, CI 1.3-1.7). When Canadian-born educators were analyzed
separately, an association was found between seropositivity and the number of
years worked in daycare centres (5-yr OR 1.3, CI 1.0-1.8). INTERPRETATION: This
represents the first study in Canada designed to examine risk factors for
previous HAV infection among adult day-care educators. As a group, their risk
factors for seropositivity are similar to those in the general population.
However, educators born in Canada (a low-endemicity area for hepatitis A) appear 
to be at additional risk by working in day-care centres. The benefits of HAV
screening and routine vaccination of day-care educators need to be examined.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15559862 [PubMed - indexed for MEDLINE]

372: Braz J Med Biol Res. 2004 Dec;37(12):1779-87. Epub 2004 Nov 17.

Genetic variability of hepatitis A virus isolates in Rio de Janeiro: implications
for the vaccination of school children.

Villar LM, Lampe E, Meyer A, Gaspar AM.

Departamento de Virologia, Instituto Oswaldo Cruz, Rio de Janeiro, RJ, Brazil.
lvillar@ioc.fiocruz.br

The epidemiology of hepatitis A virus (HAV) infection is shifting from high to
intermediate endemicity in Brazil, resulting in increased numbers of susceptible 
individuals and a greater potential for the emergence of outbreaks. Universal
vaccination against HAV has been recommended for children, but updated
sero-epidemiological data are necessary to analyze the level of natural immunity 
and to identify candidates for preventive measures. In addition, more molecular
studies are necessary to characterize the genotypes involved in HAV infections
and outbreaks. Sera from 299 school children (5-15 years old) and 25 school staff
members, collected during an outbreak of HAV at a rural public school in June
2000, were tested for IgM and total anti-HAV antibodies (ELISA). Viral RNA was
amplified by RT-PCR from anti-HAV IgM-positive sera and from 19 fecal samples.
Direct nucleotide sequencing of the VP1/2A region was carried out on 18
PCR-positive samples. Acute HAV infection was detected by anti-HAV IgM in 93/299 
children and in 3/25 adult staff members. The prevalence of total anti-HAV
antibodies in IgM-negative children under 5 years of age was only 10.5%. HAV-RNA 
was detected in 46% IgM-positive serum samples and in 16% stool samples. Sequence
analysis showed that half the isolates belonged to subgenotype IA and the other
half to IB. On the basis of these data, mass vaccination against HAV is
recommended without prevaccination screening, especially for children before they
enter school, since nearly 90% of the children under 5 years were susceptible.
Molecular characterization indicated the endemic circulation of specific HAV
strains belonging to subgenotypes IA and IB.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15558184 [PubMed - indexed for MEDLINE]

373: Digestion. 2004;70(3):187-91. Epub 2004 Nov 19.

Autoimmune hepatitis--sequel of a relapsing hepatitis A in a 75-year-old woman.

Grünhage F, Spengler U, Fischer HP, Sauerbruch T.

Department of Internal Medicine I, University of Bonn, Bonn, Germany.
frank.gruenhage@ukb.uni.bonn.de

Acute hepatitis A virus (HAV) infection is a global cause of acute hepatitis.
However, chronic HAV infection is unlikely. Nevertheless, there is some evidence 
that acute infection with HAV may trigger chronic active hepatitis which fulfils 
the criteria of autoimmune hepatitis (AIH). Whether AIH following HAV infection
is virus specific remains unclear. Despite evidence that inherited factors may
play a role in the development of autoimmunity after viral infection, the
pathomechanism remains unclear. We describe a 75-year-old woman with a history of
pulmonary sarcoidosis who developed AIH after acute HAV infection. Copyright 2004
S. Karger AG, Basel.

Publication Types: 
    Case Reports
    Review

PMID: 15557764 [PubMed - indexed for MEDLINE]

374: J Travel Med. 2004 Jul-Aug;11(4):201-6.

Immunogenicity of booster vaccination with a virosomal hepatitis A vaccine after 
primary immunization with an aluminum-adsorbed hepatitis A vaccine.

Beck BR, Hatz CF, Loutan L, Steffen R.

Department of Medical and Diagnostic Services, Swiss Tropical Institute, Basel,
Switzerland.

BACKGROUND: Increasing numbers of individuals are traveling to areas of high
hepatitis A endemicity and require immunization against the hepatitis A virus
(HAV). The option of using a virosomal, aluminum-free, HAV vaccine (Epaxal) for
booster immunization following primary vaccination with an aluminum-adsorbed
vaccine has been assessed. METHODS: In total, 142 healthy subjects, 79 men and 63
women, aged 12 to 72 years, were injected intramuscularly with a booster dose of 
Epaxal (0.5 mL containing < or =500 RIA units of HAV antigen) 6 to 24 months
after primary vaccination with Havrix (0.5 or 1.0 mL containing 720 or 1440 ELISA
units of HAV antigen, respectively, adsorbed onto aluminum hydroxide). Anti-HAV
antibody titers were measured on days 0 and 28 by an enzyme immunoassay. Adverse 
events were recorded for 1 month postinjection. RESULTS: Overall, 98/118 subjects
(83%) with no serologic evidence of past HAV infection were still seroprotected
at enrolment (anti-HAV antibody titer < or = 20 mIU/mL). The seroprotection rate 
was 87% in those primed with Havrix 1440 6 to 12 months earlier (n=93) and 60% in
those primed < or =12 months before enrolment (n=20, mean 16 months). The
geometric mean anti-HAV antibody titer increased from 65 mIU/mL at day 0 to 1,722
mIU/mL at day 28 after a single booster dose with Epaxal in evaluable subjects
who were primarily vaccinated with either a single dose of Havrix 1440 (n=111) or
two separate doses of Havrix 720 (n=4). All subjects were seroprotected at day
28, and 98% showed at least a four-fold increase in anti-HAV antibody titer.
Epaxal was well tolerated and no serious adverse events were reported. At day 28,
the tolerability of the vaccination was judged as either "very good" or "good" by
96% of vaccinees and by all investigators. CONCLUSION: Epaxal can be successfully
used to boost immunization following primary vaccination with an
aluminum-adsorbed vaccine, and is well tolerated.

Publication Types: 
    Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 15541221 [PubMed - indexed for MEDLINE]

375: World J Gastroenterol. 2004 Dec 15;10(24):3579-82.

Forecasting model for the incidence of hepatitis A based on artificial neural
network.

Guan P, Huang DS, Zhou BS.

Department of Epidemiology, School of Public Health, China Medical University,
Shenyang 110001, Liaoning Province, China.

AIM: To study the application of artificial neural network (ANN) in forecasting
the incidence of hepatitis A, which had an autoregression phenomenon. METHODS:
The data of the incidence of hepatitis A in Liaoning Province from 1981 to 2001
were obtained from Liaoning Disease Control and Prevention Center. We used the
autoregressive integrated moving average (ARIMA) model of time series analysis to
determine whether there was any autoregression phenomenon in the data. Then the
data of the incidence were switched into [0,1] intervals as the network
theoretical output. The data from 1981 to 1997 were used as the training and
verifying sets and the data from 1998 to 2001 were made up into the test set.
STATISTICA neural network (ST NN) was used to construct, train and simulate the
artificial neural network. RESULTS: Twenty-four networks were tested and seven
were retained. The best network we found had excellent performance, its
regression ratio was 0.73, and its correlation was 0.69. There were 2 input
variables in the network, one was AR(1), and the other was time. The number of
units in hidden layer was 3. In ARIMA time series analysis results, the best
model was first order autoregression without difference and smoothness. The total
sum square error of the ANN model was 9 090.21, the sum square error of the
training set and testing set was 8 377.52 and 712.69, respectively, they were all
less than that of ARIMA model. The corresponding value of ARIMA was 12 291.79, 8 
944.95 and 3 346.84, respectively. The correlation coefficient of nonlinear
regression (R(NL)) of ANN was 0.71, while the R(NL) of ARIMA linear
autoregression model was 0.66. CONCLUSION: ANN is superior to conventional
methods in forecasting the incidence of hepatitis A which has an autoregression
phenomenon.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15534910 [PubMed - indexed for MEDLINE]

376: Rom J Intern Med. 2000-2001;38-39:97-101.

Serum level of soluble intercellular adhesion molecule-1 in patients with acute
viral hepatitis A or acute viral hepatitis B: lack of correlation with severity
of the disease.

Magiera M, Kucharz EJ, Chelmicka A, Moron-Swierszcz J, Witor A, Witor A, Kotulska
A.

Department of Infectious Disease, Medical University of Silesia, 45/47, Ul.
Ziolowa, 40-635 Katowice, Poland.

Serum soluble ICAM-1 (sICAM-1) was found to be increased in patients with chronic
hepatitis. The aim of the study was the evaluation of sICAM-1 dynamics in
patients with acute hepatitis A or hepatitis B. Serum level of sICAM-1 was
determined in 13 patients with acute hepatic A, 19 patients with acute hepatitis 
B, and 20 healthy controls. Measurements were done four times, at the beginning
of jaundice, in the 14th day of jaundice, at release from the hospital, and when 
biochemical indices of the liver function became normal. An increase in sICAM-1
was shown in the patients. There was no difference between patients with
hepatitis A and those with hepatitis B. The sICAM-1 decreased in the course of
recovery but the values in the last measurements were still higher than in the
controls. There was no correlation of sICAM-1 and duration of hospitalization.
The obtained results do not suggest sICAM-1 as diagnostic or prognostic marker in
patients with acute hepatitis A or B.

PMID: 15529577 [PubMed - indexed for MEDLINE]

377: J Clin Microbiol. 2004 Nov;42(11):5121-4.

Diagnostic relevance of immunoglobulin G avidity for hepatitis A virus.

Roque-Afonso AM, Grangeot-Keros L, Roquebert B, Desbois D, Poveda JD, Mackiewicz 
V, Dussaix E.

Centre National de Référence pour les Virus à Transmission Entérique, Hôpital
Paul Brousse, Villejuif, France.

Diagnosis of acute hepatitis A virus (HAV) infection is based on the detection of
HAV immunoglobulin M (IgM). However, IgM could be detected due to nonspecific
polyclonal activation of the immune system. An avidity test for anti-HAV IgG was 
developed to distinguish acute infection, where low-avidity antibodies are
detected, from immune reactivation. The assay was tested on 104 samples,
including 11 sera from patients with past infection, 15 sera from patients with
acute infection and 4 collected after recovery, 10 sera from vaccinated subjects,
4 sera from patients with suspected immune reactivation, and 60 unselected
HAV-IgM positive sera, collected over 1 year in a routine laboratory. The avidity
index (AI) was expressed as percentage. The results were provided as the mean +/-
one standard deviation. Patients with a history of prior infection had AIs of
>70% (mean, 86% +/- 10), whereas the mean AI was 36% +/- 16 during acute HAV
infection (P < 0.001). Within the first month after the onset of hepatitis,
avidity was either noncalculable due to a very low IgG titer or <50%. In patients
with immune reactivation, avidity was >70% (88% +/- 10%), a finding consistent
with a prior infection. Among the 60 unselected sera, 35 (58%) had a
noncalculable or <50% avidity, and most of them had a detectable HAV RNA,
confirming HAV infection. In contrast, 16 (27%) had an avidity of >70%, and none 
was reverse transcription-PCR positive, suggesting immune reactivation. These 16 
patients were significantly older than the others (50 +/- 16 years versus 26 +/- 
14 years). The new anti-HAV IgG avidity assay we developed could improve HAV
infection diagnosis, particularly in elderly patients.

Publication Types: 
    Evaluation Studies

PMID: 15528704 [PubMed - indexed for MEDLINE]

378: Med J Aust. 2004 Nov 1;181(9):482-5.

Impact of hepatitis A vaccination of Indigenous children on notifications of
hepatitis A in north Queensland.

Hanna JN, Hills SL, Humphreys JL.

Tropical Public Health Unit Network, Queensland Health, PO Box 1103, Cairns, QLD 
4870, Australia. Jeffrey_hanna@health.qld.gov.au

OBJECTIVE: To describe the impact of a hepatitis A vaccination program for
Indigenous children in north Queensland. DESIGN: Enhanced surveillance of all
notified cases of hepatitis A in north Queensland from 1996 to 2003. SETTING:
North Queensland; population, 596 500 people, including about 6900 Indigenous
children aged under five years. INTERVENTIONS: Hepatitis A vaccine was provided
to Indigenous children in north Queensland from February 1999; two doses were
recommended (at 18 months and 2 years of age), as was catch-up vaccination up to 
the sixth birthday. RESULTS: In the 4 years 1996-1999, 787 cases of hepatitis A
were notified in north Queensland, 237 (30%) of which were in Indigenous people. 
The average annual notification rates in Indigenous and non-Indigenous people
during this period were 110 and 25 cases per 100 000 persons, respectively. In
the first 4 years after introduction of the vaccination program (2000-2003), 66
cases of hepatitis A were notified. Only nine of the 66 (14%) were in Indigenous 
people. The average annual notification rates in Indigenous and non-Indigenous
people in 2000-2003 were 4 and 2.5 cases per 100 000 persons, respectively.
CONCLUSION: Hepatitis A seems to have been eradicated from Indigenous communities
in north Queensland very soon after the vaccination program began. The rapid
decline in notifications in non-Indigenous as well as Indigenous people suggests 
the program quickly interrupted chains of transmission from Indigenous children
to the broader community. To our knowledge this is the first evidence that a
hepatitis A vaccination program targeting a high-risk population within a
community can reduce disease in the broader community. Hepatitis A vaccine should
be provided to other high-risk Indigenous children elsewhere in Australia.

Publication Types: 
    Evaluation Studies

PMID: 15516191 [PubMed - indexed for MEDLINE]

379: Transfusion. 2004 Nov;44(11):1555-61.

Comment in:
    Transfusion. 2005 Jun;45(6):1037-8.

Molecular and serologic tracing of a transfusion-transmitted hepatitis A virus.

Gowland P, Fontana S, Niederhauser C, Taleghani BM.

Blood Transfusion Service Berne, Swiss Red Cross, Switzerland.
peter.gowland@bsd-be.ch

BACKGROUND: The transmission of hepatitis A virus (HAV) via blood transfusion has
not been evidenced by molecular tracing so far. CASE REPORT: A 33-year-old
asymptomatic female volunteer made a whole-blood donation. Thirteen days later an
acute HAV infection was diagnosed. Retrospectively, a high viral load was
measured by quantitative reverse transcription polymerase chain reaction (RT-PCR)
in the quarantine fresh-frozen plasma (1.4 x 10(6) geq/mL), whereas
immunoglobulin M (IgM) and G (IgG)/IgM anti-HAV were not detectable and the
alanine aminotransferase levels not elevated. The red blood cells have just been 
transfused on Day 14. The 63-year-old male recipient already was HAV
seropositive. He did not develop clinical symptoms of HAV and anti-HAV IgM was
not detected. Seventy-five days later, a 25-fold increase in the anti-HAV IgG/IgM
titer was observed. Demonstrable HAV ribonucleic acid (RNA) in the recipient by
means of RT-PCR on Day 6, but not on Days 1 and 75, suggests that a transient
reinfection did occur. Analyzed sequences of the HAV RNA in the donor and
recipient were identical. CONCLUSION: For the first time, transfusion-transmitted
HAV was evidenced by molecular and serologic tracing. The transmitted HAV can
survive and replicate for a limited period despite the presence of anti-HAV IgG.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't

PMID: 15504159 [PubMed - indexed for MEDLINE]

380: Clin Infect Dis. 2004 Oct 15;39(8):1207-13. Epub 2004 Sep 24.

Safety and immunogenicity of an inactivated hepatitis A vaccine among
HIV-infected subjects.

Wallace MR, Brandt CJ, Earhart KC, Kuter BJ, Grosso AD, Lakkis H, Tasker SA.

Clinical Investigation Dept., Naval Medical Center San Diego, San Diego,
California 92134-1005, USA. MRWallace@nmcsd.med.navy.mil

BACKGROUND: Hepatitis A is a major health risk for many human immunodeficiency
virus (HIV)-infected individuals. Vaccination is a potentially attractive measure
to reduce the incidence of hepatitis A among this population, but data on its
safety and immunogenicity are incomplete. METHODS: Ninety HIV-uninfected adults
received an inactivated hepatitis A vaccine (VAQTA; Merck), and 90 HIV-infected
subjects were randomized, in double-blind fashion, to receive either the vaccine 
or placebo. The HIV-infected subjects were stratified by CD4 cell count, with 45 
subjects having CD4 cell counts of > or =300 cells/mm3 and 45 subjects having CD4
cell counts of <300 cells/mm3. Vaccine was given at weeks 0 and 24 of the
study.Results. Seroconversion rates at week 28 of the study were 94% among the
HIV-infected subjects and 100% among the HIV-uninfected control subjects.
HIV-infected subjects with CD4 cell counts of <300 cells/mm3 had a seroconversion
rate of 87%, and HIV-infected subjects with CD4 cell counts of > or =300
cells/mm3 had a seroconversion rate of 100%. The vaccine was generally well
tolerated, and no adverse effect on either HIV load or CD4 cell count was found. 
CONCLUSION: Hepatitis A vaccine was both immunogenic and safe among HIV-infected 
subjects.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 15486846 [PubMed - indexed for MEDLINE]

381: J Appl Microbiol. 2004;97(5):1105-12.

Detection of infectious hepatitis A virus by integrated cell
culture/strand-specific reverse transcriptase-polymerase chain reaction.

Jiang YJ, Liao GY, Zhao W, Sun MB, Qian Y, Bian CX, Jiang SD.

Laboratory of Vaccine Research, Institute of Medical Biology, Chinese Academy of 
Medical Science, Kunming, Yunnan Province.

AIMS: A novel integrated cell culture/strand-specific reverse
transcriptase-polymerase chain reaction (RT-PCR) assay was established for
detection of infectious hepatitis A virus (HAV). METHODS AND RESULTS: The
specificity of tagged RT-PCR was assessed using HAV genomic positive-strand RNA
extracted from HAV virions as reference. Water samples artificially contaminated 
with infectious or formalin-inactivated HAV were subjected to integrated cell
culture (ICC)/RT-PCR and ICC/strand-specific RT-PCR assays respectively. The
tagged RT-PCR had high specificity for HAV negative-strand RNA. By demonstrating 
the formation of negative-strand RNA replicative intermediate,
ICC/strand-specific RT-PCR can distinguish between infectious and non-infectious 
HAV. The described method detected infectious HAV at inoculation level of 10(0)
TCID50 per flask within 4 days. CONCLUSIONS: The ICC/strand-specific RT-PCR is a 
novel, rapid, sensitive and reliable method for detection of infectious HAV.
SIGNIFICANCE AND IMPACT OF THE STUDY: Coupled with a suitable virus concentration
and purification system, ICC/strand-specific RT-PCR will provide a novel and
rapid method for detection of infectious HAV in clinical, environmental and food 
samples. This assay may be used as an alternative method to test the effective
inactivation of inactivated virus vaccines. It may also be adapted to assess the 
efficacy of disinfection of HAV and enteric viruses in foods and water.

Publication Types: 
    Evaluation Studies

PMID: 15479428 [PubMed - indexed for MEDLINE]

382: Vaccine. 2004 Oct 22;22(31-32):4342-50.

Quantifying the impact of hepatitis A immunization in the United States,
1995-2001.

Samandari T, Bell BP, Armstrong GL.

Division of Viral Hepatitis, National Center for Infectious Diseases, Centers for
Disease Control and Prevention, 1600 Clifton Road, NE Mailstop G-37 Atlanta, GA
30333, USA.

Hepatitis A rates have declined to historically low rates in the United States.
To assess the degree to which this decline was attributable to immunization, we
correlated changes in the incidence of hepatitis A with increases in immunization
coverage in a Poisson regression model. In a model allowing for herd immunity, an
estimated 97,800 hepatitis A cases were averted due to immunization between
1995-2001, including 39% of potential cases in 2001. Assuming no herd immunity;
32,300 cases of hepatitis A would have been prevented. Sensitivity analysis
showed that the number of averted cases in this period could range from 45,500 to
172,900. Among children 2-18 years old, vaccination coverage averaged 10% in 2001
and is estimated to have prevented 51% of cases in this age group. These results 
suggest that much of the recent reduction of hepatitis A rates is attributable to
immunization and that immunization has been associated with a strong herd
immunity effect.

PMID: 15474727 [PubMed - indexed for MEDLINE]

383: New Microbiol. 2004 Jul;27(3):215-20.

The seroepidemiology of Hepatitis A virus in Amman, Jordan.

Battikhi MN, Battikhi EG.

Department of Medical Laboratory Sciences, Faculty of Allied Health Sciences,
Hashemite University, Jordan.

Hepatitis A virus (HAV) has emerged as an important public health problem in many
countries of the Middle East region and Jordan is no exception. From January 1991
to December 2001, a total of 1015 patients were diagnosed at Al-Battikhi Medical 
Laboratories. Samples were collected at seventeen private laboratories
distributed throughout areas of the Governorate of Amman (capital of Jordan). A
significant variation (P=0.03) was obtained between number of HAV cases and year.
Seasonal variation in HAV cases was seen throughout the study period with maximal
rates in the spring and summer months (P<0.001). The highest incidence rate
(9.6/100,000 population) was detected in the year 1993 and the lowest incidence
rate (1.1/100,000 population) was found in the year 2001. There was a significant
difference (P<0.0001) between number of HAV cases and age group. The highest
number of cases 166 (16.4%) was reported for age group 5-14 years and the lowest 
number of cases 18 (0.02%). Male to female ratio was 1.25: 1. There was no
significant sex variation (P=0.28). A significant variation (P=0.006) was
observed between number of HAV cases and districts. The present results suggested
a link between the age groups, year, month and occurrence of HAV infection. Male 
to female ratio indicates no significant sex variation.

PMID: 15460523 [PubMed - indexed for MEDLINE]

384: J Pediatr Gastroenterol Nutr. 2004 Oct;39(4):337-40.

Immunogenicity and safety of an inactivated hepatitis A vaccine in children with 
Down syndrome.

Ferreira CT, Leite JC, Taniguchi A, Vieira SM, Pereira-Lima J, da Silveira TR.

Pediatric Gastroenterology, Hospital de Clínicas de Porto Alegre, School of
Medicine, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
ctf@webflash.com.br

OBJECTIVES: Hepatitis A vaccine has not been investigated in children with Down
syndrome. The aim of this study was to evaluate immunogenicity and safety of an
inactivated hepatitis A vaccine in noninstitutionalized children with Down
syndrome and compare their responses to those of healthy control children.
METHODS: An open, prospective, controlled trial of 127 children ages 1 to 12
years, 63 with Down syndrome and 64 healthy control subjects, was conducted at a 
single hospital. Inactivated hepatitis A virus (HAV) vaccine containing 720
enzyme-linked immunosorbent assay units of alum-adsorbed HAV was administered
intramuscularly in a two-dose schedule at 0 and 6 months. Seroconversion and
anti-HAV titers were measured at months 1 and 7. RESULTS: Seroconversion rates at
month 1 were 92% and 94% and geometric mean titers (GMT) were 164.02 and 160.77
mIU/mL in the Down syndrome (DS) and control groups, respectively. At month 7,
seroconversion rates were 100% in both groups, with GMT of 1,719.86 and 2,344.90 
mIU/mL in the DS and control groups, respectively (P = 0.117). Both doses were
well tolerated and no significant adverse events observed. Local reaction at the 
injection site was the most common adverse event reported in both groups (15% in 
DS and 11% in controls). CONCLUSIONS: The authors' data demonstrate a good
response to HAV vaccination in children with DS living at home, with GMT not
statistically different from that of healthy control children. HAV vaccine is
well tolerated and highly immunogenic in children with DS.

PMID: 15448421 [PubMed - indexed for MEDLINE]

385: J Clin Microbiol. 2004 Sep;42(9):4329-31.

Detection of hepatitis A virus RNA in saliva.

Mackiewicz V, Dussaix E, Le Petitcorps MF, Roque-Afonso AM.

Centre National de Référence pour les Virus à Transmission Entérique (HAV),
Laboratoire de Virologie, Hôpital Paul Brousse, 94804 Villejuif, France.

Hepatitis A virus (HAV) is shed in feces but also in saliva. HAV RNA was detected
in saliva in five out of six acutely infected patients with HAV viremia. Serum
and saliva sequences were identical. The simplicity of obtaining material allows 
the recommendation of the use of saliva for investigation of outbreaks.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15365037 [PubMed - indexed for MEDLINE]

386: Vaccine. 2004 Sep 28;22(29-30):4002-13.

Critical prevalence of antibodies minimizing vaccination costs for hepatitis A,
hepatitis B, varicella, measles and tetanus in adults and adolescents in
Catalonia, Spain.

Plans-Rubió P.

Department of Health, General Direction of Public Health, Travessera de les Corts
131-159, 08028 Barcelona, Spain.

The prevalence of seropositive individuals that makes costs of vaccinating all
individuals equal to that for screening and vaccination of susceptible
individuals is defined as the critical prevalence of antibodies (p*). Screening
and vaccination is more efficient when the prevalence of seropositive individuals
(p) in the population is higher than p*. In this study, the formula to obtain p* 
was derived from the cost-effectiveness equations, showing that it depends on
screening and vaccination costs, programme compliance, screening test
performance, vaccine efficacy and disease costs. The formula was used to
determine the least costly vaccination strategy for hepatitis A and B, varicella,
measles and tetanus in adults and adolescents in Catalonia. The least costly
vaccination strategy was vaccination without screening (since p was lower than
p*) for hepatitis B, measles and tetanus in adults and adolescents (5-14 years)
and for hepatitis A in individuals aged 5-24 years, and screening and vaccination
(since p was higher than p*) for varicella in adults and adolescents and for
hepatitis A in adults aged >24 years. Vaccination strategies based on the
critical prevalence of antibodies could maximize the immunity level in the
community from available resources.

PMID: 15364450 [PubMed - indexed for MEDLINE]

387: Braz J Infect Dis. 2004 Apr;8(2):180-3. Epub 2004 Sep 8.

Acute liver failure complicating viral hepatitis A.

Diniz-Santos DR, Melo MC, Melo RF, Silva LR.

Pediatric Gastroenterology and Hepatology Division, Professor Hosannah Oliveira
Pediatric Centre, Federal University of Bahia, Salvador, BA, Brazil.

Hepatitis A is one of the most frequent infectious liver diseases affecting
children worldwide. The disease is usually mild and self-limited, and
complications are very rare. Nevertheless, hepatitis A can sometimes cause acute 
liver failure (ALF), a severe, life-threatening condition. Herein is reported a
case of a child who presented ALF during a course of hepatitis A. The need for
early identification of possible ALF cases among hepatitis A patients, and for
effective ways of evaluating such a possibility, are discussed. We also emphasize
the importance of prevention measures, especially vaccination.

Publication Types: 
    Case Reports

PMID: 15361997 [PubMed - indexed for MEDLINE]

388: J Trop Pediatr. 2004 Aug;50(4):241-2.

Thrombocytopenia in hepatitis A--an atypical presentation.

Shenoy R, Nair S, Kamath N.

Department of Pediatrics, Kasturba Medical College, Mangalore-575001, Karnataka, 
India. drshenoy2001@hotmail.com

Acute hepatitis due to hepatitis A virus (HAV) is usually a benign self-limiting 
disease during childhood. Autoimmune manifestations are rare with acute HAV,
especially in children. We report an 8-year-old boy with severe thrombocytopenia 
as an initial manifestation of acute HAV infection. Bone marrow examination
suggested peripheral destruction of platelets. His clinical course was
complicated by persistent severe thrombocytopenia and progressive cholestasis
requiring prednisolone therapy.

Publication Types: 
    Case Reports

PMID: 15357567 [PubMed - indexed for MEDLINE]

389: Clin Nephrol. 2004 Aug;62(2):138-43.

Erratum in:
    Clin Nephrol. 2005 Apr;63(4):326. Cheema, SS [removed].

IgA-dominant glomerulonephritis associated with hepatitis A.

Cheema SR, Arif F, Charney D, Meisels IS.

Division of Nephrology, St. Luke's-Roosevelt Hospital Center, College of P&S of
Columbia University, New York, NY, USA. shafiqcheema@yahoo.com

Unlike hepatitis B and C, renal involvement has been extremely uncommon in
patients with hepatitis Avirus (HAV) infection. Nephrotic syndrome has been
documented as a rare complication in association with HAV infection. In this
report, we describe a patient with serologically documented HAV infection, who
presented with nephrotic syndrome. The renal biopsy showed an immunoglobulin A-
(IgA) dominant glomerulonephritis (GN) with subendothelial immune deposits. This 
is the second biopsy-proven case report of a patient with acute HAV associated
with IgA-dominant immune complex glomerulonephritis and nephrotic syndrome. This 
is perhaps the first case in which a patient experienced both IgA-dominant
glomerulonephritis and cutaneous cryoglobulinemic vasculitis.

Publication Types: 
    Case Reports
    Review

PMID: 15356971 [PubMed - indexed for MEDLINE]

390: Allergy. 2004 Oct;59(10):1063-7.

The association of hepatitis A and Helicobacter pylori with sensitization to
common allergens, asthma and hay fever in a population of young British adults.

Jarvis D, Luczynska C, Chinn S, Burney P.

Department of Public Health Sciences, Kings College London (Guys' Campus),
London, UK.

BACKGROUND: A negative association of oro-faecally spread infection with
serological markers of sensitization and allergic disease has been reported.
METHOD: Previous infection with hepatitis A and Helicobacter pylori was assessed 
in a community-based sample of young British adults and associations with
serum-specific IgE to environmental allergens, asthma-like symptoms and hay fever
were examined. RESULTS: There was no association of previous infection with
hepatitis A or H. pylori with wheeze or hay fever. There was no evidence of an
association of infection with either agent and sensitization except for the
isolated finding of a lower prevalence of sensitization to grass in those with
IgG antibodies to H. pylori (OR 0.65, 95% CI 0.43-0.99). This association did not
explain the negative association of family size with sensitization to grass.
CONCLUSION: In this population, there was no evidence that infection with
hepatitis A or H. pylori was associated with lower levels of IgE sensitization,
asthma or hay fever except for an isolated finding of a negative association of
H. pylori infection with sensitization to grass.

PMID: 15355464 [PubMed - indexed for MEDLINE]

391: Clin Ther. 2004 Jul;26(7):1084-91.

A randomized, open-label study of the immunogenicity and reactogenicity of three 
lots of a combined typhoid fever/hepatitis A vaccine in healthy adults.

Loebermann M, Kollaritsch H, Ziegler T, Rendi-Wagner P, Chambonneau L, Dumas R,
Lafrenz M.

Department of Tropical Medicine and Infectious Diseases, Faculty of Medicine,
University of Rostock, D-18057 Rostock, Germany.
micha.loebermann@medizin.uni-rostock.de

BACKGROUND: Travelers are often advised to receive both the typhoid fever and
hepatitis A virus (HAV) vaccines, particularly when going to areas where the 2
diseases are endemic. Thus, combined administration of these vaccines could make 
immunization more acceptable by reducing the number of injections needed.
OBJECTIVE: This study compared the safety profiles and immunogenicity of 3
batches of a combined typhoid fever/HAV vaccine administered using a dual-chamber
bypass syringe. METHODS: This randomized, open-label study was conducted at 2
university-based travel clinics in Germany and Austria. Subjects received a
single IM injection from 1 of 3 batches of the combined vaccine. Blood samples
were drawn immediately before and 28 days after vaccination to evaluate the
response to the 2 antigens by assessing geometric mean titers (GMTs) and rates of
seroconversion and seroprotection. Subjects recorded all adverse events (AEs)
occurring during the study period in a diary. RESULTS: Six hundred ten healthy
adults were enrolled in the study. Twenty-eight days after vaccination, 90.6% of 
the study population had protective typhoid Vi antibody titers (> or = 1
microg/mL) and 100% had protective HAV antibody titers (> or = 20 mIU/mL).
Seroconversion rates and GMTs were not significantly different between the 3
batches. There were no differences with regard to local or systemic AEs between
the 3 batches of vaccine. There were no immediate adverse reactions (within 30
minutes of vaccination) and no serious AEs related to vaccination. Of 609
evaluable subjects (1 was lost to follow-up after the first visit), 555 (91.1%)
experienced > or = 1 local reaction within the first 7 days after vaccination,
mainly pain at the injection site (550 [90.3%]), but only 26 (4.3%) described
this pain as severe. Vaccine-related headache and mild to moderate asthenia were 
each reported by 54 subjects (8.9%). Symptoms resolved spontaneously in all
cases. CONCLUSIONS: The 3 batches of the combined typhoid fever/HAV vaccine
administered by dual-chamber bypass syringe were equally well tolerated and
effective in healthy adults, and did not differ significantly in terms of GMTs or
seroconversion rates.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 15336473 [PubMed - indexed for MEDLINE]

392: Am J Public Health. 2004 Sep;94(9):1620-6.

Hepatitis A virus immunity and seroconversion among contacts of acute hepatitis A
patients in Amsterdam, 1996-2000: an evaluation of current prevention policy.

Sonder GJ, van Steenbergen JE, Bovee LP, Peerbooms PG, Coutinho RA, van den Hoek 
A.

GG&GD, Department of Infectious Diseases, Municipal Health Service, Amsterdam,
The Netherlands. gsonder@gggd.amsterdam.nl

OBJECTIVES: We evaluated the hepatitis A virus (HAV) control policy (hygienic
precautions and passive immunization with immune globulin) for "household
contacts" (defined as all people who lived in the same house and who shared the
same toilet with the patient, people who took care of an HAV-infected child, and 
sexual partners of the patient) of acute hepatitis A patients between 1996 and
2000. METHODS: We examined the characteristics and the serological outcomes of
household contacts. All susceptible contacts were invited for retesting 6 weeks
after they received immune globulin. RESULTS: Of 1242 contacts of 569 HAV
patients, more than 50% (n = 672) were found to be HAV immune. Among the
remaining contacts, 161 (28.2%) had a concurrent infection, and 86 of these
individuals were symptomatic. The remaining 409 susceptible contacts received
immune globulin, with 186 (45%) returning for retesting 6 weeks later (64 [34%]
were infected, but only 12 had symptoms). CONCLUSIONS: Immune globulin does not
protect all household contacts from HAV infection; however, it attenuates
symptoms and effectively reduces further HAV transmission.

PMID: 15333325 [PubMed - indexed for MEDLINE]

393: Water Sci Technol. 2004;50(1):131-6.

Comparison of different primer sets for the RT-PCR detection of hepatitis A virus
and astrovirus in mussel tissues.

Romalde JL, Ribao C, Luz Vilariño M, Barja JL.

Dept de Microbiología y Parasitologia, Facultad de Biología, Universidad de
Santiago de Compostela 15782, Spain. mpromald@usc.es

In the present study, the efficiency of several primer sets for the RT-PCR
detection of hepatitis A virus (HAV) and astrovirus from both crude viral
extracts and experimentally infected shellfish tissues was evaluated. Differences
were observed depending on the primer set employed in the sensitivity of
amplification of both viral types. For HAV primers, HAV240/HAV68 yielded the
higher sensitivity: showing a detection limit of 0.02-0.1 infectious
particles/microL or mg of tissue (either crude extracts or seeded mussel
tissues). Regarding detection of AsV, a better performance was observed with
primer set A1/A2 achieving a sensitivity of 0.1-1 PFU/microL or mg of tissue. The
results obtained in this work strongly indicated that selection of primer sets to
be employed for the routine detection of enteric viruses was a critical point in 
the design of the RT-PCR protocols.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 15318498 [PubMed - indexed for MEDLINE]

394: Hepatobiliary Pancreat Dis Int. 2004 Aug;3(3):381-5.

Promoting hepatic growth factor in the treatment of heavy type hepatitis and
severe chronic hepatitis: a multicenter clinical study.

Xu JH, Yu YY, Si CW, Zeng Z, Wang QH, Luo DD, Zhou YX, Zeng MD, Qiao GY, Yao JL, 
Lu WL.

Department of Infectious Diseases, First Hospital of Beijing University, Beijing 
100034, China. ddcatjh@sina.com

BACKGROUND: The mortality rate of heavy type hepatitis is high. No special
treatment is available except general treatment. This multicenter clinical study 
was designed to observe the safety and efficacy of promoting hepatic growth
factor (PHGF) in the treatment of heavy type hepatitis and severe chronic
hepatitis. METHODS: 347 patients with heavy type hepatitis and 324 with severe
chronic hepatitis were subjected to administration of 120 microg of PHGF per day 
for 4 weeks on the basis of general treatment. Those who were being effectively
treated would last additional 2 to 4 weeks. Blood routine, urine routine, blood
urea nitrogen (BUN), blood creatinine (Cr), blood ammonia, alpha fetoprotein
(AFP), electrolyte, alanine transaminase (ALT), aspartate transaminase (AST),
serum total bilirubin (TBIL), serum direct bilirubin (DBIL), prothrombin time
activity (PTA), total protein (TP) and albumin (ALB) were detected in the
patients before treatment, 2 weeks after treatment, and at the end of the
treatment. Any side-effect would be recorded. RESULTS: In the patients with
severe chronic hepatitis, the total effective rate of the treatment was 88.9%.
The levels of ALT, AST and TBIL decreased significantly (P<0.001), whereas those 
of PTA and ALB increased significantly (P<0.001), and the level of AFP increased 
slightly. In patients with heavy type hepatitis, the total effective rate of this
treatment was 78.4%, and patients at different stage showed different results.
The total effective rates of patients with early, medium and terminal stage heavy
type hepatitis were 89.9%, 84.8% and 27.5%, respectively. No severe side-effect
was shown. CONCLUSION: PHGF is effective and safe in the treatment of patients
with heavy type hepatitis and severe chronic hepatitis. But it should be
administered early in patients with heavy type hepatitis so as to get better
curative effects.

Publication Types: 
    Clinical Trial
    Multicenter Study

PMID: 15313673 [PubMed - indexed for MEDLINE]

395: J Gastroenterol. 2004 Jul;39(7):640-8.

Comment in:
    J Gastroenterol. 2004 Jul;39(7):702-3.

Epidemiological and clinical study of sporadic acute hepatitis E caused by
indigenous strains of hepatitis E virus in Japan compared with acute hepatitis A.

Sainokami S, Abe K, Kumagai I, Miyasaka A, Endo R, Takikawa Y, Suzuki K, Mizuo H,
Sugai Y, Akahane Y, Koizumi Y, Yajima Y, Okamoto H.

First Department of Internal Medicine, Iwate Medical University, Morioka, Japan.

BACKGROUND: We compared acute hepatitis E (AH-E) and acute hepatitis A (AH-A) to 
investigate the epidemiology, clinical features, and prognosis of AH-E caused by 
an indigenous hepatitis E virus (HEV) in Japan. METHODS: We enrolled 58 patients 
diagnosed with AH-A or AH-E (32 men and 26 women; age, 20-72 years) from December
1997 to October 2002. Phylogenetic analysis of the partial 412-nucleotide
sequence of open reading frame (ORF) 2 was performed in patients with AH-E.
RESULTS: Regarding the geographic distribution of the HEV genotype, genotype III 
was principally distributed in Honshu Island, and genotype IV in Hokkaido Island 
( P = 0.0034). The phylogenetic analysis of the ORF2 region revealed that there
were significant geographic differences in the distribution of the HEV strains in
Japan, with some strains being widespread and some, localized. In comparison with
AH-A patients, those with AH-E were older (56.1 +/- 10.6 vs 45.9 +/- 10.8 years; 
P = 0.0017). The proportion of males among patients with AH-E was significantly
higher ( P = 0.0001). Pyrexia was often observed in AH-A, and malaise in AH-E.
Laboratory data indicate that AH-E induces a weak immunological reaction, whereas
jaundice appears earlier in AH-E than in AH-A. One patient with AH-E died of
acute hepatic failure, but none of those with AH-A died during the study period. 
CONCLUSIONS: Our results suggest that there are geographical differences between 
HEV strains in Japan, and that AH-E is more common in males and older patients
than AH-A. Laboratory data indicate a weak immunological reaction and early
appearance of jaundice in AH-E.

Publication Types: 
    Comparative Study

PMID: 15293134 [PubMed - indexed for MEDLINE]

396: Commun Dis Public Health. 2004 Jun;7(2):134-7.

Immunity and exposure to hepatitis A virus in pre-adolescent children from a
multi-ethnic inner city area.

Morris-Cunnington M, Edmunds WJ, Miller E.

Immunisation Division, Health Protection Agency, London.
marianne.c.cunnington@gsk.com

Seroprevalence data among ethnic minority groups within England and Wales are
rare. An opportunistic approach was taken to test residual oral fluid, collected 
from pre-adolescent school children from an ethnically diverse region of
northwest England, for anti-hepatitis A virus (HAV) IgG. Individual data on
ethnicity and country of birth were also available. Of the 257 children who
consented to participate, 62% were of South Asian ethnic origin. The overall
seroprevalence was 18.8%, higher than 13.1% reported from a recent
population-based survey in England and Wales among a mainly Caucasian population 
of the same age. The only factor significantly associated with HAV seropositivity
in a multivariable logistic regression model was birth of the child abroad.
Association with the place of birth of the child, but not that of the parent
indicates that infection within this group occurs mainly abroad. Larger studies
among ethnic minority groups are needed to investigate this claim further.

PMID: 15259416 [PubMed - indexed for MEDLINE]

397: Transplant Proc. 2004 Jun;36(5):1500-1.

Prevalence of previous hepatitis A virus infection in renal transplant patients
with hepatitis C: evidence of persistent anti-hepatitis A virus immune response.

Mariya FA, de Mello Perez R, Silva AE, Pestana JO, Ferraz ML.

Division of Gastroenterology, Universidade Federal de São Paulo, Brazil.

Data concerning the prevalence of hepatitis A virus (HAV) infection among kidney 
transplant recipients are scarce. There is little information concerning natural 
immunity acquired after acute HAV infection. In most renal transplant recipients,
anti-HAV antibodies are not detectable after vaccination; it is reasonable to
suppose that immunosuppressive therapy interferes with the immunity. The
objective of this study was to evaluate, in an endemic area, the prevalence of
anti-HAV immunoglobulin (Ig)G in renal transplant recipients with chronic
hepatitis C virus (HCV) infection. The prevalence of anti-HAV IgG was assessed in
40 HCV-positive renal transplant recipients. This group showed a 90% prevalence
of previous HAV infection. These findings suggest that in an endemic area, the
prevalence of previous HAV infection is high, even among immunosuppressed
patients. HAV antibodies acquired after natural infection are detectable even
after the onset of immunosuppressive therapy. These data should be considered
when renal transplant recipients are considered for HAV vaccination.
Prevaccination screening of renal transplant recipients must follow the same
guidelines as those for immunocompetent subjects. Copyright 2004 Elsevier Inc.

PMID: 15251370 [PubMed - indexed for MEDLINE]

398: Am J Public Health. 2004 Jun;94(6):996-1001.

Hepatitis A incidence and hepatitis a vaccination among American Indians and
Alaska Natives, 1990-2001.

Bialek SR, Thoroughman DA, Hu D, Simard EP, Chattin J, Cheek J, Bell BP.

Division of Viral Hepatitis, Mail Stop G-37, Centers for Disease Control and
Prevention, 1600 Clifton Road NE, Atlanta, GA 30333, USA. zqg7@cdc.gov

OBJECTIVES: We assessed the effect on trends in hepatitis A incidence of the 1996
recommendation for routine hepatitis A vaccination of American Indian/Alaska
Native (AIAN) children. METHODS: We examined trends in hepatitis A incidence
among AIAN peoples during 1990-2001 and vaccination coverage levels among
children on the largest American Indian reservation. RESULTS: Hepatitis A rates
among AIANs declined 20-fold during 1997-2001. Declines in hepatitis A incidence 
occurred among AIANs in reservation and metropolitan areas. Among 1956 children
living on the Navajo Nation whose medical records were reviewed, 1508 (77.1%) had
received at least one dose of hepatitis A vaccine, and 1020 (52.1%) had completed
the vaccine series. CONCLUSIONS: Hepatitis A rates among AIAN peoples have
declined dramatically coincident with implementation of routine hepatitis A
vaccination of AIAN children.

Publication Types: 
    Comparative Study
    Research Support, U.S. Gov't, P.H.S.

PMID: 15249305 [PubMed - indexed for MEDLINE]

399: Int J Infect Dis. 2004 Jul;8(4):201-9.

Hepatitis A outbreaks--methods of intervention in South-East Asian countries.

David AM; The Steering Committee for Prevention and Control of Infectious
Diseases.

College of Medicine, University of the Philippines, Manila, Philippines.
amdavid@ite.net

INTRODUCTION: In many Asian countries, improved hygiene standards and
socio-economic conditions have led to a reduction in exposure to the hepatitis A 
virus (HAV) in childhood. However, the persistence of circulating HAV may lead to
hepatitis A outbreaks, particularly in adolescents and adults. In other countries
and specific areas, where socio-economic conditions have not improved as
markedly, HAV endemicity remains medium-to-high. A systematic approach to
outbreak control is therefore urgently needed. METHODS: The Steering Committee
for Prevention and Control of Infectious Diseases reviewed reports on recent
hepatitis A outbreaks in South-East Asian countries and determined that there is 
no systematic regional plan for the containment of such outbreaks. By contrast,
on reviewing reports on outbreaks in several North American and European
countries, it was found that the most important elements of successful outbreak
control are a plan of action, rapid and widespread communication, public
education and vaccination of household contacts to prevent secondary cases.
RESULTS: This investigation proposes an outbreak control programme consisting of 
six key stages -- initiation, planning, set-up, implementation, vaccination of
at-risk populations and evaluation. Outbreak control requires the formation of an
outbreak management team, plus a task force to implement intervention and educate
the public. The vaccination of family members and close contacts is a central
element of the programme. CONCLUSION: This model programme for hepatitis A
outbreak control provides a framework for action in countries and specific areas 
where the disease remains a problem.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 15234323 [PubMed - indexed for MEDLINE]

400: J Coll Physicians Surg Pak. 2004 Jun;14(6):348-50.

Hepatitis A--frequency in children with non-specific abdominal symptoms.

Malik R, Ghafoor T, Sarfraz M, Hasan N.

Department of Paediatrics, Combined Military Hospital, Peshawar.

OBJECTIVE: To study the frequency of subclinical hepatitis 'A' in children having
non-specific abdominal symptoms. DESIGN: A descriptive study. PLACE AND DURATION 
OF STUDY: This study was conducted at Combined Military Hospital (CMH), Peshawar 
from June to December 2000. SUBJECTS AND METHODS: Three hundred and sixty
children of either gender, < 12 years of age, presenting with vague abdominal
symptoms and no jaundice were evaluated for hepatitis. Eighty eight (24.4%)
children meeting the inclusion criteria of elevated serum alanine
aminotransferase (ALT), twice the upper limits of normal (90 IU/L), and normal
serum bilirubin were labelled as subclinical hepatitis. RESULTS: A total of 360
children were evaluated for vague abdominal symptoms and 96 (26.7%) of them had
hepatitis on laboratory profile. Eight patients developed early jaundice and were
excluded from the study. Out of 88 (24.4%) cases of subclinical hepatitis, 82
(93.2%) had hepatitis-A, 03 (3.4%) had hepatitis-B, while no causative agent was 
found in 03 (3.4%) children. The common presenting symptoms were abdominal
pain/discomfort, loss of appetite, nausea, vomiting, malaise, fatigue and fever. 
Hepatomegaly and splenomegaly was documented in 56% and 43% cases respectively. A
history of exposure to a patient with hepatitis was present in 14/88 (15.9%)
cases whereas no child was vaccinated against HAV. Serum ALT level declined to
normal limits within 4 weeks for 77/88 (87.5%) cases and within 6 weeks for 84/88
(95.4%). All cases recovered spontaneously with out any complication. CONCLUSION:
Hepatitis-A was rampant in children presenting with vague abdominal symptoms in
our series.

PMID: 15233888 [PubMed - indexed for MEDLINE]

401: Eur J Epidemiol. 2004;19(5):461-5.

Assessment of HAV and HEV seroprevalence in children living in post-earthquake
camps from Düzce, Turkey.

Sencan I, Sahin I, Kaya D, Oksuz S, Yildirim M.

Department of Clinical Microbiology and Infectious Disease, AIBU Düzce Medical
School, Düzce, Turkey. isencan@ibuduzce-tip.edu.tr

The aim of the study was to investigate the prevalance of enterically transmitted
hepatitis among children living in post-earthquake camps, and to assess the
efficacy of the measurements during and after the disaster in Düzce and Golyaka. 
In the second half of 1999, North-western Turkey, was struck by two massive
earthquakes in less than 3 months. The first, on 17 August 1999, involving
Golyaka, was struck, measuring between 7.4 and 7.8 on the Richter scale.
Irregularity about providing clean water and necessary sanitary facilities were
observed after the first earthquake because of confusion. The second quake, on 12
November 1999, which rated 7.2 on the Richter scale, shook Düzce. Necessary
precautions were applied rapidly at the second quake about shelter, clean
drinking water, food and control of distribution of the aids by government and
civil aid organisations. Anti-HEV(IgG) and anti-HAV(IgG) antibodies were
determined in 476 sera of the children who was living in six camps. HAV
prevalence of the children who were living in Düzce and Golyaka temporary houses 
was 44.4 and 68.8% respectively, OR: 0.37, CI 95%: 0.22-0.61, p = 0.0005. HEV
prevalence of the children was 4.7 and 17.2% respectively, OR: 0.24, CI 95%:
0.11-0.51, p = 0.0007. In conclusion, HAV and HEV prevalence of children were
lower than that in endemic areas but higher than that in developed countries.
This study has pointed out the importance of providing urgent need of the
sufficient sanitary facilities after disasters for preventing or reducing the
incidence of enterically transmitted hepatitis, especially in the regions which
were at risk for various disasters. Essential precautions such as providing clean
water and food supply must be taken and an emergency action plan for preventing
the infectious disease must be prepared before disasters such as earthquakes.

Publication Types: 
    Comparative Study
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 15233319 [PubMed - indexed for MEDLINE]

402: Pediatrics. 2004 Jul;114(1):e68-73.

Hepatitis A in Hispanic children who live along the United States-Mexico border: 
the role of international travel and food-borne exposures.

Weinberg M, Hopkins J, Farrington L, Gresham L, Ginsberg M, Bell BP.

Division of Global Migration and Quarantine, Centers for Disease Control and
Prevention, Atlanta, Georgia 30333, USA. mpw5@cdc.gov

OBJECTIVES: Hispanic children who live along the United States-Mexico border
historically have had among the highest hepatitis A rates in the United States,
but risk factors have not been well characterized. The objective of this study
was to examine risk factors associated with acute hepatitis A virus (HAV)
infection in Hispanic children who live along the United States-Mexico border in 
San Diego County, California. METHODS: In this case-control study, hepatitis A
cases among Hispanic children who were younger than 18 years reported from June
1998 through August 2000 were matched by age group and exposure period to
Hispanic children who were susceptible to HAV infection. Participants and their
families were interviewed about demographic information and potential sources of 
HAV infection, including attending child care, food and waterborne exposures,
cross-border and other international travel, and travel-related activities.
RESULTS: Participants included 132 children with hepatitis A and 354 control
subjects. The median age of study participants was 7 years (range: 1-17).
Sixty-seven percent of case-patients traveled outside the United States during
the incubation period, compared with 25% of the children without hepatitis A
(odds ratio [OR]: 6.3; 95% confidence interval [CI]: 4.0-9.7); all children,
except 1, had traveled to Mexico. In multivariate analysis, hepatitis A was
associated with having eaten food from a taco stand or street food vendor
(adjusted OR: 17.0; 95% CI: 4.1-71.1) and having eaten salad/lettuce (adjusted
OR: 5.2; 95% CI: 1.3-20.1) during travel. CONCLUSIONS: Hepatitis A among Hispanic
children who live in an urban area of the United States-Mexico border is
associated with cross-border travel to Mexico and food-borne exposures during
travel. Travelers to areas where hepatitis A is endemic should receive hepatitis 
A vaccine before travel.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15231975 [PubMed - indexed for MEDLINE]

403: Pediatr Infect Dis J. 2004 Jun;23(6):586-8.

Possible association of Guillain-Barré syndrome and hepatitis A vaccination.

Blumenthal D, Prais D, Bron-Harlev E, Amir J.

Department of Pediatrics C, Schneider Children's Medical Center of Israel, Petah 
Tiqva, Israel.

We report a case of Guillain-Barré syndrome in a previously healthy child who
received a hepatitis A vaccination (HAVRIX) 5 days before onset of symptoms. No
other precipitating factor could be identified. The relevant literature is
reviewed and discussed.

Publication Types: 
    Case Reports
    Review

PMID: 15194849 [PubMed - indexed for MEDLINE]

404: Pediatr Infect Dis J. 2004 Jun;23(6):571-4.

Immunogenicity of inactivated hepatitis A vaccine in children with chronic liver 
disease.

Majda-Stanislawska E, Bednarek M, Kuydowicz J.

Department and Clinic of Infectious Diseases and Hepatology, Medical University
of Lodz, Lodz, Poland.

One and 6 months after vaccination with hepatitis A virus vaccine (HAVRIX 720
Junior), immunologic responses (anti-hepatitis A virus >/=20 mIU/ml) in children 
with chronic hepatitis C infection seroprotection were 92% (23/25) and 75% (9/12)
in children with chronic hepatitis B infection 87% (21/24) and 88% (15/17) and in
healthy children 91% (20/22) at both times. A booster dose induced seroprotection
in all children.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 15194843 [PubMed - indexed for MEDLINE]

405: Infection. 2004 Jun;32(3):149-52.

Erratum in:
    Infection. 2004 Aug;32(4):249.

Rapid antibody response after vaccination with a virosomal hepatitis a vaccine.

Ambrosch F, Finkel B, Herzog C, Koren A, Kollaritsch H.

Dept. of Specific Prophylaxis and Tropical Medicine, Institute of
Pathophysiology, University of Vienna, Impfzentrum Nord, Austria.
f.ambrosch@impfzentrum.at

BACKGROUND: This study was designed to assess the early antibody kinetics after a
priming dose, and the extent of the antibody increase after a booster dose of an 
inactivated virosomal hepatitis A virus (HAV) vaccine (Epaxal). PATIENTS AND
METHODS: This was an open, uncontrolled study in 30 healthy subjects. The vaccine
was injected intramuscularly on day 1 and month 12. Serum antibody titers were
measured by ELISA on day 1 (pre dose) and at various time points thereafter until
month 12 (pre-booster dose). After the booster dose, antibody titers were
measured at various intervals until month 24. Neutralizing antibody titers were
measured in 12 subjects a number of times during the 1st month by an antibody
neutralization assay. Titers > or = 10 mIU/ml were considered seroprotective.
RESULTS: ELISA antibody titers showed a rapid increase post vaccination. By day
15, 96% of subjects were seroprotected, which increased to 100% by day 22 (n = 27
evaluable subjects, aged 18-43 years; 13 male, 14 female). All subjects achieved 
seroprotective HAV-neutralizing antibody titers by day 11 (n = 12). The booster
vaccination at month 12 resulted in a strong response in all subjects, with a
sustained anti-HAV antibody titer (1,155 mIU/ml) at month 24. Both the priming
and booster doses were well tolerated. CONCLUSION: Primary vaccination with this 
virosomal HAV vaccine is well tolerated and induces a rapid HAV-neutralizing
antibody response resulting in seroprotection in all subjects within 10 days. In 
addition, the booster vaccination results in prolonged seroprotective antibody
levels. Copyright Urban and Vogel

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15188074 [PubMed - indexed for MEDLINE]

406: Ann Trop Paediatr. 2004 Jun;24(2):141-4.

Acute disseminated encephalomyelitis associated with hepatitis A virus infection.

Alehan FK, Kahveci S, Uslu Y, Yildirim T, Yilmaz B.

Division of Child Neurology, Department of Paediatrics, Faculty of Medicine,
Başkent University, 6 cadde 72/3 Bahcelievler, Ankara 06490, Turkey.
falehan@hotmail.com

We describe the case of a 30-month-old boy who developed acute disseminated
encephalomyelitis (ADEM) after hepatitis A virus (HAV) infection and ultimately
died. As far as we know, this is only the second case of HAV-associated ADEM to
be reported in the literature. The child was brought to hospital with fever,
lethargy and weakness of 2 days duration. He had developed jaundice, abdominal
pain and malaise 2 weeks beforehand and these problems had resolved within 2
days. Neurological examination revealed lethargy, generalised weakness and
positive Babinski's signs bilaterally. Cerebrospinal fluid examination showed
mild lymphocytic pleocytosis, increased protein and elevated anti-HAV IgM and IgG
titres. Serum HAV IgM and IgG titres were also elevated. Despite aggressive
treatment with ceftriaxone, acyclovir and anti-oedema measures, he developed
papilloedema and coma within 24 hours of admission. Magnetic resonance imaging of
the brain revealed diffuse cerebral oedema and multifocal hyperintensities on
T2-weighted images, with most lesions in the white matter of both cerebral
hemispheres. The diagnosis of ADEM was established and high-dose steroids and
intravenous immunoglobulin were added to the treatment regimen. However, his
clinical condition continued to deteriorate and he died on the 20th day in
hospital. This case shows that HAV infection can be linked with ADEM. Patients
with HAV infection should be examined carefully for central nervous system
symptoms during follow-up. Likewise, the possibility of HAV infection should be
investigated in cases of ADEM.

Publication Types: 
    Case Reports

PMID: 15186542 [PubMed - indexed for MEDLINE]

407: J Clin Microbiol. 2004 Jun;42(6):2825-8.

Outbreak of infection with hepatitis A virus (HAV) associated with a foodhandler 
and confirmed by sequence analysis reveals a new HAV genotype IB variant.

Chironna M, Lopalco P, Prato R, Germinario C, Barbuti S, Quarto M.

Hygiene Section, Department of Internal Medicine and Public Health, University of
Bari, Policlinico Piazza G, Cesare 11, 70124 Bari, Italy.
m.chironna@igiene.uniba.it

An outbreak of infection with hepatitis A virus associated with a foodhandler and
involving 26 subjects occurred in Southern Italy. Sequence analysis of the
VP3-VP1 and VP1-P2A junctions confirmed that the outbreak was due to a point
source and allowed the identification of a new genotype IB variant. This report
confirms the usefulness of sequence-based molecular fingerprinting during
outbreaks.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15184483 [PubMed - indexed for MEDLINE]

408: J Med Virol. 2004 Jul;73(3):378-83.

Genetic analysis of hepatitis A virus isolates from Brazil.

de Paula VS, Lu L, Niel C, Gaspar AM, Robertson BH.

Department of Virology, Oswaldo Cruz Institute, Rio de Janeiro, Brazil.

A limited number of hepatitis A virus (HAV) isolates from South America have been
characterised at the genomic level. IgM anti-HAV positive serum samples collected
from patients with hepatitis A living in the five geographical regions of Brazil 
(North, Northeast, Central, South, and Southeast) were used to obtain HAV
isolates and determine their genetic relatedness. Of the 232 case isolates,
sequence data were obtained from the VP1/2A junction region of the HAV genome.
All isolates were classified in genotype I; 231 belonged to subgenotype IA, and
one to subgenotype IB. HAV isolates from four States formed distinct clusters of 
highly related sequences. However, isolates from other states did not cluster and
the sequences from those states were intermingled with sequences found in the
other states. The amino acid sequences of all but two isolates showed a Leu -->
Ile substitution at position 42 in the 2A protein. This substitution appeared to 
be a characteristic geographic fingerprint of HAV sequences within Brazil.
Copyright 2004 Wiley-Liss, Inc.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15170631 [PubMed - indexed for MEDLINE]

409: New Microbiol. 2004 Apr;27(2):119-24.

A comparison of RT-PCR-based assays for the detection of HAV from shellfish.

Di Pinto A, Conversano MC, Forte VT, La Salandra G, Montervino C, Tantillo GM.

Dipartimento di Sanità e Benessere degli Animali, Università degli Studi, Bari,
Italy.

The hepatitis A virus (HAV) is the most common cause of viral infection linked to
shellfish consumption. The lack of correlation between the fecal coliform
indicators and the presence of enteric viruses in shellfish and their harvesting 
waters points to the need for molecular methods to detect viruses. We compared
two RT-PCR based techniques currently available for the detection of the
hepatitis A virus (HAV) in shellfish. Both approaches involve extraction of viral
particles by glycine buffer and concentration of virus particles by one or two
PEG precipitation steps. One procedure involves as RNA extraction method the use 
of oligo (dT) cellulose to select poly (A) RNA, and the other uses a system in
which total RNA is bound on silica membrane. Comparison of the two RT-PCR based
methods highlighted the efficiency of the first approach which is less
time-consuming and technically demanding than the second.

Publication Types: 
    Comparative Study

PMID: 15164621 [PubMed - indexed for MEDLINE]

410: J Gastroenterol Hepatol. 2004 Mar;19 Suppl:S13-6.

Hepatitis disease management programs in Malaysia.

Khairullah NS, Merican DI.

Ministry of Health Malaysia, Infectious Disease Research Center, Institute for
Medical Research, Jalan Pahang, Malaysia. norshahidah@imr.gov.my

The MLF since its inception in 1996 has endeavored to develop a coordinated
approach towards the improved care and treatment of liver diseases in Malaysia.
Its close liaison with the Malaysian MOH, local medical associations, and
corporate bodies has contributed to the success of its many programs. Educating
the public, research, and training have been important elements of successful
hepatitis disease control programs. Hepatitis Days have been proven to be very
successful in raising the awareness of the general public to hepatitis disease.
Rapid screening and vaccination has also helped to remove the social stigma
associated with the disease, eliminated the need for numerous clinic
appointments, and rendered vaccination more accessible to the public. The MLF
perspective emphasizes the need for collaborative effort between Government
bodies and other agencies, such as non-governmental organizations, laboratories, 
and the medical fraternity, to ensure the overall success of hepatitis disease
management programs.

PMID: 15156929 [PubMed - indexed for MEDLINE]

411: J Community Health. 2004 Jun;29(3):245-64.

Concerns about infectious hepatitis and Delacorte's Welfare Island Fountain.

Spiegel AD, Kavaler F, Metz AA.

State University of New York, Downstate Medical Center, College of Medicine,
Brooklyn, New York 11203, USA.

In 1969, philanthropist George T. Delacorte donated a spectacular water fountain 
to New York City on the southern tip of Welfare Island. Architects designed the
fountain's jet geyser to pump a plume of water from the East River more than 400 
feet into the air. Public health experts feared that the water from the heavily
polluted East River could be a possible source for the spread of infectious
hepatitis. Water droplets could be airborne by the prevailing winds to land on
the densely populated east side of Manhattan. Upon the insistence of the New York
City Department of Health, the fountain's water intake source was chlorinated.
This action was initiated before the discovery of the hepatitis A virus (HAV) in 
1973. A miscellany of continuing problems plagued the fountain for about two
decades, causing the donor to label the fountain "Delacorte's Folly." Eventually,
Delacorte gave up. In the late 1980s, the fountain ceased spouting and was
finally dismantled.

Publication Types: 
    Historical Article

PMID: 15141899 [PubMed - indexed for MEDLINE]

412: Vaccine. 2004 May 7;22(15-16):1862-7.

Pharmaco-economic evaluation of targeted hepatitis A vaccination for children of 
ethnic minorities in Amsterdam (The Netherlands).

Postma MJ, Bos JM, Beutels P, Schilthuis H, van den Hoek JA.

Groningen University Institute for Drug Exploration/University of Groningen
Research Institute of Pharmacy (GUIDE/GRIP), Groningen, The Netherlands.

OBJECTIVE: Estimate cost-effectiveness of vaccination against hepatitis A virus
(HAV) for children of ethnic minorities in Amsterdam. BACKGROUND:
Pharmaco-economic analysis is relevant for motivating reimbursement of
vaccination costs in the framework of a programmatic approach to vaccination of
ethnic minorities. DESIGN: Pharmaco-economic modeling. METHOD: In
cost-effectiveness analysis, costs, benefits and health gains were estimated for 
a large-scale HAV-vaccination for children of Turkish and Maroccan origin.
Analysis was performed from the societal perspective, as recommended in the Dutch
guidelines for pharmaco-economic research. This implies that indirect costs of
production losses are included in the analysis. Cost-effectiveness was expressed 
in net costs per adult HAV-infection averted in incremental and aggregate
analysis. Incremental analysis compares targeted vaccination with the current
limited-scale HAV-vaccination that exists, whereas aggregate analysis compares
targeted vaccination with the sheer absence of vaccination. RESULTS: Net
aggregate costs of targeted HAV-vaccination for Turkish and Maroccan children in 
Amsterdam amounts to 61.000. Cost-effectiveness was estimated, in aggregate and
incremental analysis, at 13.500 and 11.100 respectively per adult HAV-infection
averted. Uni- and multivariate sensitivity analyses show that major impact on
cost-effectiveness may be expected from reductions in the vaccine price through
economies of scale. Probabilistic sensitivity analysis indicates possible large
fluctuations in cost-effectiveness from 1 year to another, related to varying
incidence of disease. CONCLUSION: HAV-vaccination for children from ethnic
minorities in Amsterdam is not cost saving, but may have a favourable
cost-effectiveness. Such a vaccination program fits into the recent Dutch policy 
of specific vaccinations directed at groups of ethnic minorities, such as for
hepatitis B.

PMID: 15121296 [PubMed - indexed for MEDLINE]

413: J Viral Hepat. 2004 May;11(3):277-82.

Hepatitis A virus and injecting drug misuse in Aberdeen, Scotland: a case-control
study.

Roy K, Howie H, Sweeney C, Parry J, Molyneaux P, Goldberg D, Taylor A.

Centre for Infection and Environmental Health, Glasgow, UK.
kirsty.roy@scieh.csa.scot.nhs.uk

To describe an epidemiological investigation of an outbreak of hepatitis A virus 
(HAV) infection among injecting drug users in Aberdeen, Scotland. A case-control 
study to determine whether transmission was facilitated by poor personal hygiene 
or through sharing injecting equipment. Cases were more likely to report not
washing their hands after using the toilet [odds ratio (OR) = 12.9, 95%
confidence interval (CI) = 1.58-105.89] or before preparing food (OR = 4.0, 95%
CI = 1.01-15.8), and less likely to have washed their hands prior to preparing
drugs (OR = 10.67, 95% CI = 2.14-53.07). Cases were also more likely to report
recipient sharing of needles/syringes (OR = 8.27, 95% CI = 1.68-40.57), and to
have had injecting contact with someone who was jaundiced (OR = 29.4, 95% CI =
3.18-271.44). The results indicate that the lack of hygiene within the context of
individuals gathering to prepare and inject drugs provides ample opportunity for 
the transmission of HAV. Although the promotion of good hygiene and the avoidance
of sharing injecting equipment are important measures in preventing HAV
transmission, they are unlikely to effect major behavioural change. Such measures
should, therefore, be reinforced by routinely offering HAV vaccine to injectors.

Publication Types: 
    Case Reports

PMID: 15117332 [PubMed - indexed for MEDLINE]

414: Eur J Epidemiol. 2004;19(3):275-8.

Age-specific seroprevalence of hepatitis A infection among children visited in
pediatric hospitals of Tehran, Iran.

Mehr AJ, Ardakani MJ, Hedayati M, Shahraz S, Mehr EJ, Zali MR.

Research Center for Gastroenterology and Liver Disease, Taleghani Hospital,
Tehran, Iran. ajfmehr@yahoo.com

BACKGROUND: Hepatitis A is an enterically transmitted disease that still remains 
endemic in many developing countries. In some countries improvements in living
conditions have recently led to changing in epidemiology of hepatitis A virus
(HAV) infection. In our country there are very few reports on prevalence of HAV
infection. OBJECTIVE: To determine the seroprevalence of anti-HAV IgG among
children visited in pediatric hospitals of Tehran, Iran. METHODS: The study group
included 1018 children who were 6 months-14.9 years of age. These children were
visited in four major pediatric hospitals of Tehran. The children were separated 
to three age groups: Group 1 (6 months-4.9 years; n = 469), Group 2 (5.0-9.9
years; n = 290), and Group 3 (10.0-14.9 years; n = 259). Serum anti-HAV IgG was
tested with commercial ELISA kits. The data were tested for statistical
significance with chi2 test. RESULTS: In all subjects, seroprevalence of
hepatitis A was 22.3% (95% CI: 19.7, 24.9). There was no significant difference
between genders (22.2% vs. 22.5% in males and females, respectively) and among
age groups (Group I was 22.1% and Group 3 was 25.9; p > 0.05). CONCLUSIONS: In
summary, it seems that HAV infection is not highly endemic at least in some urban
areas of Iran. On the basis of this epidemiologic data, post exposure prophylaxis
would be necessary for children and young adults, and hepatitis A vaccination
strategy should be revised.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15117123 [PubMed - indexed for MEDLINE]

415: Eur J Epidemiol. 2004;19(3):267-73.

The epidemiology of hepatitis a virus infection in children, in Edirne, Turkey.

Erdoğan MS, Otkun M, Tatman-Otkun M, Akata F, Türe M.

Kocaeli University Medical Faculty, Department of Public Health, Kocaeli, Turkey.
sarper.erdogan@isbank.net.tr

Turkey is a middle endemic area with respect to Hepatitis A virus (HAV)
infection. However, the frequency of this infection varies due to socio-economic 
differences in various regions. The aim of this study was to detect the most
likely age of exposure to HAV and factors affecting infection rates among
children living in Edirne. A sample of 645 children between the ages of 0-19
living in Edirne were tested for total anti-HAV levels using ELISA method. A
questionnaire on socio-economic status (SES), possible risk factors, and place of
residence was completed for each child. Anti-HAV seropositivity was found to be
4.4, 25, 37.3 and 43.2%, in 2-5, 6-10, 11-14 and 15-19 age groups, respectively. 
Seropositivity was found to be increasing with age (p < 0.05). According to
logistic regression analysis results; mother's education, SES of family, history 
of hepatitis in primary family members and the number of brothers or sisters were
determined as factors increasing the seropositivity of HAV. Furthermore, HAV
infection risk was found to be a decreasing function of income that is higher the
income less likely the infection. These results showed that HAV infection rate in
Edirne is in middle endemicity and the most likely way of exposure is
transmission from family members. Although it requires further cost-effectiveness
studies, our results indicate that applying the HAV vaccination in early
childhood would be beneficial to decrease the prevalence of the infection and
prevent HAV epidemics.

Publication Types: 
    Comparative Study

PMID: 15117122 [PubMed - indexed for MEDLINE]

416: Southeast Asian J Trop Med Public Health. 2003 Sep;34(3):569-76.

Sero-epidemiological study of hepatitis A virus infection among hill-tribe youth 
and household environmental sanitation, a hill-tribe community in northern
Thailand.

Luksamijarulkul P, Tongpradit S, Vatanasomboon P, Utrarachkij F.

Department of Microbiology, Faculty of Public Health, Mahidol University,
Bangkok, Thailand. pipatl@thaimail.com

A cross-sectional analytic study of 190 hill-tribe youth in a community in the
north of Thailand was conducted to investigate the sero-prevalence of HAV and
factors related to positive anti-HAV antibody. The studied youth, whose ages
ranged from 15 to 24 years, were interviewed about socio-economic status and
personal hygiene. Blood specimens were collected to detect anti-HAV by ELISA
commercial kit. Household environmental sanitation conditions were observed and
drinking water samples were screened for bacterial contamination using SI2
medium. Following the anti-HAV assay, the studied youth were divided into two
groups: anti-HAV positive, and anti-HAV negative. The studied variables of the
two groups were analyzed by chi2 test to find factors related to anti-HAV
positivity. The results revealed that 87% of the studied youth were positive for 
anti-HAV. There was no statistically significant difference between age
group/gender and anti-HAV positivity, p = 0.46 and 0.16, respectively.
Approximately 35.79 to 45.79% washed their hands with soap before preparing food,
before eating and after using the latrine. About 88% did not improve the
potability of their drinking water. The results of screening for bacterial
contamination in drinking water samples found that 73.53% were contaminated with 
coliform bacteria. Factors related to positive anti-HAV antibody included monthly
income, number of household members, use of latrine, hand-washing with soap after
using latrine, household refuse management and control of insects and rodents; p 
= 0.04, 0.007, 0.013, 0.008, <0.001 and <0.001, respectively. The findings
suggested that appropriate household environmental management should be improved 
in this community to reduce HAV transmission.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15115130 [PubMed - indexed for MEDLINE]

417: J Travel Med. 2004 Mar-Apr;11(2):102-6.

An estimate of the incidence of hepatitis A in unimmunized Canadian travelers to 
developing countries.

Teitelbaum P.

Riverside Travel Medicine Clinic, Ottawa, Ontario, Canada.

BACKGROUND: There is a paucity of data describing the risk of acquiring hepatitis
A while traveling in the developing world. This paper uses available data to
calculate the risk to Canadian travelers. METHODS: Information was gathered from 
Canadian and international sources on the following: the yearly incidence of
hepatitis A among Canadians; the proportion of cases of hepatitis A associated
with travel to developing countries; the number of days of such travel by
Canadians per year; and the percentage of travelers immunized before departure.
Calculations were performed on these figures to arrive at an estimated risk of
infection for unimmunized Canadian travelers. RESULTS: The annual incidence of
hepatitis A in Canada over the period 1996-2001, adjusted for underreporting,
averaged 6.15 cases/100,000 people. During that time, Canadians traveled
approximately 36.5 million days/year in developing countries. The literature
shows that 4% to 28% (mean 16%) of cases are estimated to have been acquired
abroad. It also shows that 14% to 24% (mean 19%) of such travelers are immunized 
before departure. Based on these figures, the risk of acquiring hepatitis A
during 1 month of travel in the developing world is calculated to be
approximately 1 case per 3,000 unimmunized travelers. CONCLUSION: Hepatitis A is 
an important travel-related disease, preventable by immunization. However, our
calculations indicate that the risk of acquiring hepatitis A while traveling in
the developing world is lower than some previously published estimates. The
results represent an average for all types of travel to all such countries. The
actual risk will vary considerably, depending on the destination and style of
travel.

PMID: 15109475 [PubMed - indexed for MEDLINE]

418: J Clin Gastroenterol. 2004 May-Jun;38(5):440-8.

Occupational risk for hepatitis A: a literature-based analysis.

Keeffe EB.

Stanford University School of Medicine, Stanford, CA, USA. ekeeffe@stanford.edu

Hepatitis A virus is the most frequently occurring vaccine-preventable disease.
Although generally self-limiting, acute hepatitis A is associated with
substantial morbidity and related economic burden. Hepatitis A virus is
transmitted by the fecal-oral route, and children are a main source of infection.
Some occupational workers are at risk for hepatitis A virus infection based on
the potential for contact with infected fecal matter and, in many regions in the 
United States and other developed countries, low overall rates of natural
immunity. These at-risk occupations include daycare providers, hospital workers
who have direct patient contact (nurses, nurses' aides, laundry workers), and
sewage workers. Additionally, food handlers, particularly in the hospital
setting, should be vaccinated if seronegative for hepatitis A virus because of
their ability to rapidly spread disease among vulnerable populations if infected.

Publication Types: 
    Meta-Analysis

PMID: 15100525 [PubMed - indexed for MEDLINE]

419: Drug Alcohol Depend. 2004 Apr 9;74(1):85-8.

Immunogenicity, reactogenicity and adherence with hepatitis A vaccination among
drug users.

Quaglio G, Pajusco B, Civitelli P, Migliozzi S, Des Jarlais DC, Romanò L, Lechi
A, Mezzelani P, Lugoboni F.

Medical Service for Addictive Disorders, Department of Internal Medicine,
University of Verona, Verona 37134, Italy.

Hepatitis A virus (HAV) vaccination is recommended in drug users (DUs) because
this population has a very high prevalence of hepatitis C virus, and additional
infection with HAV can lead to increased morbidity and mortality. The efficacy of
hepatitis A vaccine (1440 ELISA units), in terms of immunogenicity,
reactogenicity and compliance among 44 heroin DUs using a 0-6 month schedule was 
investigated. Three subjects (6.8%) experienced adverse reactions. After the
first dose of hepatitis A vaccine, 37% of subjects seroconverted. Two months
after the 6-month booster vaccination, all vaccinated patients became
seropositive. The mean serum antibody concentration was 40 mIU/ml after 6 months 
and 558 mIU/ml after 8 months. Although all DUs proved seropositive after the
booster vaccination, the seroconversion rate, at the 2 and 6 months time points
was much lower than in healthy subjects. The lower geometric mean titre could
affect the kinetics of decrease of antibody titres and the protection conferred
by vaccination may be less durable in these patients. These findings indicate
that the 0-12 months schedule could be reduced to a shorter 0-6 months schedule
in order to shorten the unprotected period. Further studies among drug users are 
needed to explore the efficacy and immunogenicity of higher doses or alternative 
schedules of HAV vaccine.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 15072811 [PubMed - indexed for MEDLINE]

420: Am J Epidemiol. 2004 Apr 15;159(8):786-94.

A population-based seroprevalence study of hepatitis A virus using oral fluid in 
England and Wales.

Morris-Cunnington MC, Edmunds WJ, Miller E, Brown DW.

Communicable Disease Surveillance Centre, Health Protection Agency, London, UK.
marianne.c.cunnington@gsk.com

Population-based seroprevalence studies provide important data on susceptible
groups and the potential for future outbreaks. However, the invasive nature of
serum collection has limited studies. This paper describes the first postal
population-based survey using noninvasive oral fluid technology to collect
antibody prevalence data in conjunction with extensive risk factor data to assess
the distribution of immunity to common viral infections in England and Wales.
These results pertain to hepatitis A virus (HAV). Approximately 5,500 oral fluid 
samples were collected between August 2001 and May 2002, as well as individual
risk factor data through a questionnaire, from persons aged less than 45 years
randomly sampled from general practices countrywide. Samples were tested for
immunoglobulin G-specific antibody marking a past infection or immunity to HAV
using an antibody-capture enzyme-linked immunosorbent assay. The age-specific HAV
seroprevalences indicated a low incidence of infection (overall seroprevalence of
18.9% (95% confidence interval: 17.0, 20.9) and of 9.2% (95% confidence interval:
7.1, 11.3) after the exclusion of vaccinees). Vaccination proved the most
important determinant of seropositivity. Ethnic minority groups were
underrepresented, and adjustment increased the overall prevalence to 20.1% and to
12.1% in unvaccinated individuals. The availability of comprehensive risk factor 
data allowed the description of two risk profiles related to natural infection
and vaccination.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15051588 [PubMed - indexed for MEDLINE]

421: Asia Pac J Public Health. 2003;15(2):94-8.

Measuring the impact of hepatitis A virus in Chinese cities: a life table
approach.

Lai D, Hardy RJ.

School of Public Health, The University of Texas Health Science Centre, Houston
77030, USA. dlai@sph.uth.tmc.edu

The infection of hepatitis A virus is an important public health problem in
China. In 1990, a survey on seroprevalence of anti-hepatitis A was conducted in
eight large cities of population size between one to four million. The results
were used to analyze the impact of hepatitis A. In our study, we used life table 
techniques to determine the impact that the hepatitis A virus (HAV) has on these 
eight cities by computing the expected years of life with anti-hepatitis A virus.
We compared the results from our approach with those from a previous method. The 
expected years of life with anti-hepatitis A virus were 53.82, 54.65, 44.26,
53.89, 46.18, 55.77, 55.31 and 49.89 for the eight cities (Xi'an, Huhehaote,
Chongqing, Nanjing, Jinan, Ha'erbin, Fuzhou and Nanchang), respectively. The
hepatitis A virus had the greatest impact in Ha'erbin in northeastern China;
whereas, the impact was lowest in Chongqing in southwestern China. However, based
on the previous indicator, Chongqing was ranked the highest among these cities.
Through our comparative study of the methods, our approach provides a better
measure on the burden of the disease than the previous method. It also identifies
subgroups of the population where the disease has its greatest impact on the
population.

PMID: 15038682 [PubMed - indexed for MEDLINE]

422: Health Policy. 2004 Mar;67(3):265-9.

Prevalence of anti-HAV and anti-HEV antibodies in Konya, Turkey.

Atabek ME, Fýndýk D, Gulyuz A, Erkul I.

Department of Paediatrics, School of Medicine, Selcuk University, Konya 38039,
Turkey. meatabek@hotmail.com

OBJECTIVE: To determine the prevalence of antibodies to hepatitis A (HAV) and E
(HEV) viruses in the different areas of Konya. METHODS: Anti-HAV and anti-HEV
antibodies were investigated in 210 healthy children randomly selected (100 from 
rural areas and 110 from urban areas of Konya). None gave a history of previous
icterus nor other signs of hepatitis, had received blood transfusion and HAV
vaccine, or had been on hemodialysis. RESULTS: Evidence of HAV infection occurred
in children under the age of 6 years. The seroprevalence rate was 67.8% in rural 
areas and 25.8% in urban areas. This increased rapidly with age and became
universal after 11 years of age in both areas. In contrast, HEV infections were
not detected until children were 6-11 year olds, and the 5.2% seroprevalence rate
in urban areas and 8.5% seroprevalence rate in rural areas in this age group did 
not significantly increase in older age group. The prevalence of anti-HAV as well
as anti-HEV was significantly higher in children with poor socio-economic
conditions in both areas. CONCLUSIONS: These results suggest that HAV infection
in rural areas of Konya is widespread and that environmental and socio-economic
factors play a major role in its transmission. In contrast, hepatitis E is not a 
public health problem in Konya.

PMID: 15036814 [PubMed - indexed for MEDLINE]

423: Pediatr Neurol. 2004 Mar;30(3):207-9.

Acute disseminated encephalomyelitis following hepatitis A virus infection.

Tan H, Kiliçaslan B, Onbaş O, Büyükavci M.

Department of Pediatric Neurology, Atatürk University Faculty of Medicine,
Erzurum, Turkey.

Acute disseminated encephalomyelitis is an immune-mediated demyelinating disorder
usually encountered in children or adolescents and characterized by multifocal
neurologic deficits of rapid onset. It is often preceded by various infectious
diseases or vaccination, but acute disseminated encephalomyelitis developing
after hepatitis A virus infection is rare. We present such a case in a 9-year-old
patient who illustrates the importance of considering acute disseminated
encephalomyelitis in patients who develop multifocal neurologic signs after
hepatitis A virus infection. We suggest that patients with acute disseminated
encephalomyelitis be screened for hepatitis A virus because of the occurrence of 
asymptomatic hepatitis A virus infection.

Publication Types: 
    Case Reports

PMID: 15033204 [PubMed - indexed for MEDLINE]

424: Prev Med. 2004 Apr;38(4):503-9.

The role of mobile phones in improving vaccination rates in travelers.

Vilella A, Bayas JM, Diaz MT, Guinovart C, Diez C, Simó D, Muñoz A, Cerezo J.

Adults Vaccination Centre, Preventive Medicine Department, UASP IDIBAPS, Clínic
Hospital, Barcelona, Spain.

RATIONALE: Noncompliance with vaccination schedules undermines the potential
benefits of immunization. The purpose of this study was to evaluate whether a
reminder of the next vaccine dose sent by the Short Messaging Service (SMS) to
the vaccinee's mobile phone increases compliance with hepatitis A + B and
hepatitis A vaccination schedule. SUBJECTS AND METHODS: In this experimental,
controlled study, the study group comprised travelers who went to the
Internacional-Clínic Vaccination Centre between the 1st June and 30th September
of 2001 for the standard immunization schedule against hepatitis A + B and
against hepatitis A. Trained health-care workers entered the data into a computer
to generate text messages reminding vaccinees of their scheduled doses. Two
control groups, one from the same period of the same year including travelers
from the third office (Control 2001) and the second, all travelers seen in the
same period of the previous year (Control 2000), were used. RESULTS: For the
second hepatitis A + B dose, compliance in the study group (Message Groups) was
88.4% (83.3-92.2); in the Control 2001, 80.7% (76.3-84.4, relative risk [RR] 1.10
[1.02-1.17]); and in the Control 2000, 77.2% (73.3-80.5, RR 1.15 [1.07-1.22]).
For the third hepatitis A + B vaccine dose, results were 47.1% (40.5-53.8); 26.9%
(22.8-31.7, RR 1.75 [1.41-2.17]); and 23.6% (20.1-27.4, RR 2.00 [1.63-2.45]),
respectively. As for the hepatitis A vaccine, compliance rates for the second
dose were 27.7% (23.9-31.9); 16.4% (14.4-18.6, RR 1.69 [1.40-2.04]); and 13.2%
(11.6-14.9, RR 2.10 [1.75-2.54]); respectively. CONCLUSIONS: SMS seems to be an
effective tool for increasing compliance with vaccination schedules.

Publication Types: 
    Clinical Trial
    Controlled Clinical Trial

PMID: 15020186 [PubMed - indexed for MEDLINE]

425: J Clin Virol. 2004 Apr;29(4):254-9.

Detection of hepatitis A virus RNA in serum during the window period of
infection.

de Paula VS, Villar LM, Morais LM, Lewis-Ximenez LL, Niel C, Gaspar AM.

Department of Virology, Oswaldo Cruz Institute, Avenida Brasil 4365, 21045-900
Rio de Janeiro (RJ), Brazil.

BACKGROUND: Hepatitis A virus (HAV) infection is the leading cause of clinically 
apparent viral hepatitis in many parts of the world, including developed and
developing countries. Only limited information is available regarding the
seronegative viremic window that follows HAV infection, and no systematic search 
has been reported for HAV RNA positive, IgM anti-HAV negative serum samples
during hepatitis A outbreaks. OBJECTIVES: To determine the proportion of HAV
infected individuals among (i) children who were tested negative for anti-HAV
antibodies during hepatitis A outbreaks which occurred in a public school (n =
157) and a child care center (n = 38); (ii) subjects (n = 46) initially
classified as acute non-A-C hepatitis patients after clinical examination and
serological tests (sporadic cases). STUDY DESIGN: Reverse transcription (RT)-PCR 
was performed to detect the presence of HAV genome in serum samples collected
from anti-HAV negative, susceptible subjects. RESULTS: HAV RNA was detected in
19/157 (12%) and 5/38 (13%) anti-HAV negative children from the public school and
child care center, respectively. Twelve (26%) out of the 46 acute hepatitis
patients (sporadic cases) were also HAV RNA positive. From nine of these 12
patients, a second blood sample was obtained 18-34 days after the first one: all 
nine had seroconverted to IgM anti-HAV, and their serum transaminases had reached
elevated levels (mean ALT, 418; mean AST, 241). CONCLUSIONS: Detection of HAV RNA
before IgM anti-HAV seroconversion may be used as an early diagnosis method
during hepatitis A outbreaks. HAV RNA testing should also help to elucidate acute
hepatitis cases of unknown etiology.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15018853 [PubMed - indexed for MEDLINE]

426: Clin Diagn Lab Immunol. 2004 Mar;11(2):392-8.

High prevalence of antibodies to hepatitis A and E viruses and viremia of
hepatitis B, C, and D viruses among apparently healthy populations in Mongolia.

Takahashi M, Nishizawa T, Gotanda Y, Tsuda F, Komatsu F, Kawabata T, Hasegawa K, 
Altankhuu M, Chimedregzen U, Narantuya L, Hoshino H, Hino K, Kagawa Y, Okamoto H.

Division of Virology, Department of Infection and Immunity, Jichi Medical School,
Tochigi-Ken 329-0498, Japan.

The prevalence of infection with hepatitis A virus (HAV), HBV, HCV, HDV, and HEV 
was evaluated in 249 apparently healthy individuals, including 122 inhabitants in
Ulaanbaatar, the capital city of Mongolia, and 127 age- and sex-matched members
of nomadic tribes who lived around the capital city. Overall, hepatitis B surface
antigen (HBsAg) was detected in 24 subjects (10%), of whom 22 (92%) had
detectable HBV DNA. Surprisingly, HDV RNA was detectable in 20 (83%) of the 24
HBsAg-positive subjects. HCV-associated antibodies were detected in 41 (16%) and 
HCV RNA was detected in 36 (14%) subjects, none of whom was coinfected with HBV, 
indicating that HBV/HCV carriers account for one-fourth of this population.
Antibodies to HAV and HEV were detected in 249 (100%) and 28 (11%) subjects,
respectively. Of 22 HBV DNA-positive subjects, genotype D was detected in 21
subjects and genotype F was detected in 1 subject. All 20 HDV isolates recovered 
from HDV RNA-positive subjects segregated into genotype I, but these differed by 
2.1 to 11.4% from each other in the 522- to 526-nucleotide sequence. Of 36 HCV
RNA-positive samples, 35 (97%) were genotype 1b and 1 was genotype 2a. Reflecting
an extremely high prevalence of hepatitis virus infections, there were no
appreciable differences in the prevalence of hepatitis virus markers between the 
two studied populations with distinct living place and lifestyle. A nationwide
epidemiological survey of hepatitis viruses should be conducted in an effort to
prevent de novo infection with hepatitis viruses in Mongolia.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15013993 [PubMed - indexed for MEDLINE]

427: Eur J Clin Microbiol Infect Dis. 2004 Apr;23(4):300-9. Epub 2004 Mar 6.

Aventis Pasteur vaccines containing inactivated hepatitis A virus: a compilation 
of immunogenicity data.

Vidor E, Dumas R, Porteret V, Bailleux F, Veitch K.

Aventis Pasteur, Medical Department, Clinical Development, 57 Avenue Leclerc,
69007 Lyon, France. Emmanuel.Vidor@aventis.com

Inactivated hepatitis A vaccines were developed in the 1980s and were introduced 
during the early 1990s. The Aventis Pasteur (AvP) inactivated hepatitis A virus
antigen is used in several different vaccine formulations licensed for adults and
children. Presented here are the immunogenicity results compiled from 37 clinical
trials performed in 20 different countries between 1991 and 2001 in which these
vaccines were administered to adults (16 years of age and over), children (aged
12 months-17 years), and infants (younger than 12 months). The accumulated
clinical experience with these hepatitis A virus-containing vaccines demonstrates
the excellent immunogenicity of this antigen in a wide range of situations. As
with other licensed inactivated hepatitis A vaccines, immunological priming is
achieved in virtually all vaccinees after a single-dose primary immunization, and
it may be reinforced by a booster vaccination administered 6-36 months after the 
primary vaccination.

Publication Types: 
    Comparative Study
    Review

PMID: 15007703 [PubMed - indexed for MEDLINE]

428: Nephrology (Carlton). 2004 Feb;9(1):44-6.

Acute renal tubular injury with acute hepatitis A infection: is it just a
coincidence?

Shroff GR, Badve SV, Joshi AG, Desai DC, Abraham P, Sirsat RA.

Department of Nephrology, PD Hinduja National Hospital and Medical Research
Centre, Mahim, Mumbai, India.

Acute renal failure has rarely been reported in association with acute hepatitis 
A infection. The commonest form of renal injury in such patients has been found
to be acute tubular necrosis. We report two cases of hepatitis A infection in
which acute renal failure occurred very early in the course of the illness and
had a clinical presentation and recovery pattern suggestive of acute tubular
necrosis. In both patients, the clinical course of renal dysfunction was almost
parallel to the course of hepatic dysfunction. Patient 1 needed dialysis, whereas
patient 2 did not need dialysis and had a very rapid recovery from renal function
in spite of having more severe azotaemia. Patient 2 was administered
acetylcysteine in high doses for suspected fulminant hepatic failure. A potential
benefit of a high dose of acetylcysteine in recovery of renal function from acute
tubular necrosis is postulated.

Publication Types: 
    Case Reports

PMID: 14996309 [PubMed - indexed for MEDLINE]

429: Clin Infect Dis. 2004 Mar 1;38(5):705-15. Epub 2004 Feb 11.

Hepatitis A transmitted by food.

Fiore AE.

Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta,
GA 30333, USA. afiore@cdc.gov

Hepatitis A is caused by hepatitis A virus (HAV). Transmission occurs by the
fecal-oral route, either by direct contact with an HAV-infected person or by
ingestion of HAV-contaminated food or water. Foodborne or waterborne hepatitis A 
outbreaks are relatively uncommon in the United States. However, food handlers
with hepatitis A are frequently identified, and evaluation of the need for
immunoprophylaxis and implementation of control measures are a considerable
burden on public health resources. In addition, HAV-contaminated food may be the 
source of hepatitis A for an unknown proportion of persons whose source of
infection is not identified.

PMID: 14986256 [PubMed - indexed for MEDLINE]

430: J Med Virol. 2004 Apr;72(4):538-44.

Epidemiology of hepatitis A and hepatitis E infection and their determinants in
adult Chinese community in Hong Kong.

Wong KH, Liu YM, Ng PS, Young BW, Lee SS.

Special Preventive Programme, Department of Health, Hong Kong Special
Administrative Region, Hong Kong. khwong@dhspp.net

Current epidemiology of hepatitis A virus (HAV) and hepatitis E virus (HEV) in
Hong Kong was evaluated in 936 adult Chinese subjects recruited through a
telephone interview in 2001. Some 15% of the subjects had IgG antibodies to both 
HAV and HEV while 665 (71.0%) and 176 (18.8%) had anti-HAV and anti-HEV,
respectively. Age was the most significant independent factor. Six hundred
thirty-eight (79.8%) and 165 (20.7%) subjects aged > or =30 had anti-HAV and
anti-HEV, respectively, as compared with 27 (19.7%) and 11 (8.0%) in people aged 
<30. The corresponding adjusted Odds ratio (OR) was 14.94 (95% CI: 9.13-24.44;
P<0.001) for anti-HAV positivity and 2.99 (95% CI: 1.58-5.67; P=0.001) for
anti-HEV positivity. Subjects born outside Hong Kong were more likely to have
anti-HAV (adjusted OR: 3.41; 95% CI: 2.21-5.26; P<0.001) but not anti-HEV.
Non-labour work people were less likely to have anti-HAV-adjusted OR, 0.40 (95%
CI: 0.26-0.62; P<0.001). Age-specific HAV prevalence right shifted in the last 20
years. Anti-HAV positivity was less frequent, across all age groups, in subjects 
>21-years-old in the present study than another study done in 1987-89 (P<0.001). 
HAV prevalence only increased slightly in every 10-year age groups of people aged
21-50 when compared with their corresponding 10-year-younger age groups (P=0.11),
suggesting an ageing cohort effect with no major infections in the last decade.
For HEV, both the overall and age-specific prevalence decreased over the last
decade (P<0.001). The increasing proportion of susceptible population to
enterically transmitted viral hepatitis has implications to future prevention and
control programmes, including vaccination strategies. Copyright 2004 Wiley-Liss, 
Inc.

PMID: 14981755 [PubMed - indexed for MEDLINE]

431: J Med Virol. 2004 Apr;72(4):533-7.

Hepatitis in Albanian children: molecular analysis of hepatitis A virus isolates.

Gabrieli R, Sanchez G, Macaluso A, Cenko F, Bino S, Palombi L, Buonomo E, Pinto
RM, Bosch A, Divizia M.

Department of Public Health, Faculty of Medicine, Hygiene Chair, Rome, Italy.

Hepatitis A is a common disease in developing countries and Albania has a high
prevalence of this disease associated to young age. In spite of the occurrence of
a unique serotype there are different genotypes classified from I to VII.
Genotype characterisation of HAV isolates circulating in Albania has been
undertaken, as well as the study of the occurrence of antigenic variants in the
proteins VP3 and VP1. To evaluate the genetic variability of the Albanian
hepatitis A virus (HAV) isolates, samples were collected from 12 different
cities, and the VP1/2A junction amplified and sequenced. These sequences were
aligned and a phylogenetic analysis performed. Additionally, the amino half
sequence of the protein VP3 and the complete sequence of the VP1 was determined. 
Anti-HAV IgM were present in 66.2% of all the sera. Fifty HAV isolates were
amplified and the analysis revealed that all the isolates were sub-genotype IA
with only limited mutations. When the deduced amino acid sequences were obtained,
the alignment showed only two amino acids substitutions at positions 22 and 34 of
the 2A protein. A higher genomic stability of the VP1/2A region, in contrast with
what occurs in other parts of the world could be observed, indicating high
endemicity of HAV in Albania. In addition, two potential antigenic variants were 
detected. The first at position 46 of VP3 in seven isolates and the second at
position 23 of VP1 in six isolates. Copyright 2004 Wiley-Liss, Inc.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 14981754 [PubMed - indexed for MEDLINE]

432: Am J Trop Med Hyg. 2004 Jan;70(1):83-8.

Prevalence of infection with waterborne pathogens: a seroepidemiologic study in
children 6-36 months old in San Juan Sacatepequez, Guatemala.

Steinberg EB, Mendoza CE, Glass R, Arana B, Lopez MB, Mejia M, Gold BD, Priest
JW, Bibb W, Monroe SS, Bern C, Bell BP, Hoekstra RM, Klein R, Mintz ED, Luby S.

Foodborne and Diarrheal Diseases Branch, Division of Bacterial and Mycotic
Diseases, National Center for Infectious Diseases, Centers for Disease Control
and Prevention, Atlanta, Georgia 30333, USA. ellen.stevenson@choa.org

Water and sanitation interventions in developing countries have historically been
difficult to evaluate. We conducted a seroepidemiologic study with the following 
goals: 1) to determine the feasibility of using antibody markers as indicators of
waterborne pathogen infection in the evaluation of water and sanitation
intervention projects; 2) to characterize the epidemiology of waterborne
diarrheal infections in rural Guatemala, and 3) to measure the age-specific
prevalence of antibodies to waterborne pathogens. Between September and December 
1999, all children 6-36 months of age in 10 study villages were invited to
participate. We collected sufficient serum from 522 of 590 eligible children, and
divided them into six-month age groups for analysis (6-12, 13-18, 19-24, 25-30,
and 31-36 months). The prevalence of antibodies was lowest in children 6-12
months old compared with the four older age groups for the following pathogens:
enterotoxigenic Escherichia coli (48%, 81%, 80%, 77%, and 83%), Norwalk virus
(27%, 61%, 83%, 94%, and 94%), and Cryptosporidium parvum (27%, 53%, 70%, 67%,
and 73%). The prevalence of total antibody to hepatitis A virus increased
steadily in the three oldest age groups (40%, 28%, 46%, 60%, and 76%). In
contrast, the prevalence of antibody to Helicobacter pylori was relatively
constant in all five age groups (20%, 19%, 21%, 25%, and 25%). Serology appears
to be an efficient and feasible approach for determining the prevalence of
infection with selected waterborne pathogens in very young children. Such an
approach may provide a suitable, sensitive, and economical alternative to the
cumbersome stool collection methods that have previously been used for evaluation
of water and sanitation projects.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 14971703 [PubMed - indexed for MEDLINE]

433: Curr Opin Pediatr. 2004 Feb;16(1):89-93.

The changing picture of hepatitis A in the United States.

Jenson HB.

Department of Pediatrics and Center for Pediatric Research, Eastern Virginia
Medical School and Children's Hospital of The King's Daughters, Norfolk, 23507,
USA. Hal.Jenson@EVMS.edu

PURPOSE OF REVIEW: Hepatitis A causes approximately half of the cases of viral
hepatitis in the United States. Since 1999, routine hepatitis A immunization of
children in areas of the United States with high rates of hepatitis A has been
recommended. RECENT FINDINGS: There has been an increasing appreciation of the
role of young children with asymptomatic or inapparent infection as the community
reservoir of hepatitis A virus. Epidemiologic studies have demonstrated striking 
geographic variations in the incidence of hepatitis A in the United States. On
the basis of this understanding, recommendations for control of hepatitis A were 
updated in 1999 to include routine vaccination of children living in states,
counties, and communities with high rates of hepatitis A. Routine hepatitis A
vaccination of children in areas with high rates of hepatitis A is a
cost-effective strategy to reduce the incidence of hepatitis A. SUMMARY: Improved
understanding of the epidemiology and transmission of hepatitis A combined with
the availability of effective hepatitis A vaccines have dramatically reduced the 
burden of hepatitis A in the United States.

Publication Types: 
    Review

PMID: 14758121 [PubMed - indexed for MEDLINE]

434: J Infect Dis. 2004 Feb 1;189(3):471-82. Epub 2004 Jan 23.

Two years' prospective collection of molecular and epidemiological data shows
limited spread of hepatitis A virus outside risk groups in Amsterdam, 2000-2002.

van Steenbergen JE, Tjon G, van den Hoek A, Koek A, Coutinho RA, Bruisten SM.

Division of Public Health, Gemeentelijke Geneeskundige en Gezondheidsdienst
Amsterdam, The Netherlands. Jvansteenbergen.LCI@ggd.nl

We performed a viral sequencing study on samples representing all reported
primary cases of acute hepatitis A virus (HAV) infection reported for 2 years in 
Amsterdam. Two regions of HAV RNA were amplified, sequenced, and used for
phylogenetic analysis. Of 156 cases, strains of 104 isolates (66.6%) clustered
into 3 genotypes: 1A, 1B, and 3. Two separate transmission circles occurred,
without mutual interrelation. In genotype 1A, 4 clusters occurred in men having
sex with men (MSM), and the fifth cluster was related to a virus from Morocco. In
genotype 1B, 6 small clusters were directly related to the Moroccan virus. In
genotype 3, strains were related to a virus from Pakistan. Our analysis indicates
that, to stop transmission of HAV in Amsterdam, the entire MSM population and
travelers to countries where HAV is endemic, especially children, should be
vaccinated. Prevention strategies need not include the vaccination of all
children living in Amsterdam.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 14745705 [PubMed - indexed for MEDLINE]

435: J Trop Pediatr. 2003 Dec;49(6):333-9.

Immunogenicity and safety of two doses of a paediatric hepatitis A vaccine in
thai children: comparison of three vaccination schedules.

Lolekha S, Pratuangtham S, Punpanich W, Bowonkiratikachorn P, Chimabutra K, Weber
F.

Ramathibodi Hospital, Bangkok, Thailand. rasll@mahidol.ac.th

As fewer children in Thailand are exposed to hepatitis A virus (HAV) and so do
not have seroprotective anti-HAV antibodies, they are becoming an important
source of HAV transmission. A flexible HAV vaccination schedule would facilitate 
incorporation of the vaccine into existing immunization programmes, and we
compared the immunogenicity and safety of three HAV immunization schedules. An
open, randomized, clinical trial was carried out in which healthy children were
given a primary dose of the inactivated hepatitis A vaccine, Avaxim 80
paediatric, with a booster dose 6, 12 or 18 months later. Anti-HAV geometric mean
concentrations (GMC), seroconversion rates, and GMC ratios (GMCR) of the three
schedules were compared and reactogenicity was evaluated. Seroconversion rates
were above 98 per cent (per group) up to the booster. The three schedules were
equivalent in terms of GMCRs, each eliciting a large booster effect. Local
reactions were reported for fewer than 9 per cent of each group after dose one
and less frequently after the booster dose. Injection site pain, gastrointestinal
tract disorders and fever were the most commonly reported adverse events. No
vaccine-related serious adverse events were reported. It was concluded that the
hepatitis A vaccine, Avaxim 80 paediatric, is safe and immunogenic when given as 
a two-dose schedule to healthy seronegative children aged 5-10 years, with the
second dose given at either 6, 12 or 18 months after the first.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial

PMID: 14725410 [PubMed - indexed for MEDLINE]

436: Expert Rev Vaccines. 2003 Oct;2(5):661-72.

Hepatitis A and considerations regarding the cost-effectiveness of vaccination
programs.

Deneke MG, Arguedas MR.

Department of Internal Medicine University Of Alabama at Birmingham, Birmingham, 
AL 35294, USA.

Hepatitis A vaccines have demonstrated a high degree of immunogenicity and an
excellent safety profile. Immunization of certain populations and patient
subgroups is recommended according to specific epidemiological and clinical
factors, such as a greater likelihood of acquisition of infection or concerns
regarding the risk of development of fulminant hepatitis and death. Therefore,
the economic implications of routine and/or targeted vaccination programs in the 
general population and high-risk individuals have been examined. In this
manuscript, the available data from the literature regarding the
cost-effectiveness of hepatitis vaccination programs in healthy individuals and
in those with chronic liver disease are reviewed.

Publication Types: 
    Review

PMID: 14711327 [PubMed - indexed for MEDLINE]

437: J Med Virol. 2004 Feb;72(2):197-202.

Seroprevalence of hepatitis A virus antibodies in Turkish and Moroccan children
in Rotterdam.

Richardus JH, Vos D, Veldhuijzen IK, Groen J.

Department of Infectious Diseases, Municipal Health Service, Rotterdam, The
Netherlands. richardush@ggd.rotterdam.nl

Seasonal fluctuations in hepatitis A have been observed in the Netherlands
related to Turkish and Moroccan children after visiting their home countries.
This study determined the prevalence and associated factors of hepatitis A virus 
(HAV) antibodies in Turkish and Moroccan children in Rotterdam. A random sample
was taken of children in Rotterdam, aged 5-16 years, of Turkish and Moroccan
origin, together with a random sample of native Dutch children aged 5-7 and 14-16
years. Blood was collected by finger prick on filter paper. IgG and IgM anti-HAV 
was detected by an enzyme-linked immunoassay (EIA). The 319 Turkish, 329
Moroccan, and 248 native Dutch children participated in the study. In Turkish
children, IgG anti-HAV increased from 2.2% to 22.2% over the age groups. In
Moroccan children, IgG anti-HAV increased from 10.2% to 57.7%. In native Dutch
children, 0.8% had IgG anti-HAV in the youngest and 3.1% in the oldest age group.
The percentage IgG-positive also having IgM anti-HAV was 21% in Turkish, and 41% 
in Moroccan children. No IgG-positive native Dutch children had IgM anti-HAV. The
prevalence of IgG anti-HAV was associated with increased age, being Moroccan,
longer stay in the country of origin before migrating to the Netherlands, and
known contact to HAV. The majority of Turkish and Moroccan children aged 4-16
years in Rotterdam are not protected against HAV, but do have a high risk of
becoming infected while visiting their native country. Active vaccination against
HAV of these children is indicated, with as primary aim their own protection.
Prevention of HAV-transmission in the general community should be seen as a
secondary benefit. In addition, possible Dutch contacts of nonvaccinated Turkish 
and Moroccan children, such as day care workers and teachers, should also be
vaccinated against HAV. Copyright 2004 Wiley-Liss, Inc.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 14695660 [PubMed - indexed for MEDLINE]

438: J Med Virol. 2004 Feb;72(2):194-6.

Hepatitis A vaccine: indirect evidence of immune memory 12 years after the
primary course.

Van Herck K, Van Damme P, Lievens M, Stoffel M.

Centre for the Evaluation of Vaccination, University of Antwerp, Belgium.
koen.vanherck@ua.ac.be

Vaccine-induced hepatitis A antibodies persist up to 10 years in adults, with
mathematical models estimating further persistence up to 20-25 years. Thirty-one 
adults received booster inoculations 12 years after their initial vaccination
(Havrix 720 El.U at months 0, 1, 6). At the time of booster inoculation, all
still had detectable antibodies. All but one subject met pre-defined criteria for
anamnestic response 14 days after the booster, and all subjects did so after 30
days. The subjects' geometric mean titre (GMT) increased rapidly from 242 IU/L at
baseline to 3,832 IU/L at day 14 and 5,282 IU/L at day 30. This study shows a
substantial immune response to re-exposure to hepatitis A antigen after 12 years,
which occurs rapidly to ensure protection within the average incubation period of
hepatitis A virus. Copyright 2004 Wiley-Liss, Inc.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 14695659 [PubMed - indexed for MEDLINE]

439: Int J Food Microbiol. 2004 Jan 1;90(1):23-41.

Foodborne viruses: an emerging problem.

Koopmans M, Duizer E.

National Institute of Public Health and the Environment (RIVM), Antonie van
Leeuwenhoeklaan, 9, NL-3720 BA Bilthoven, The Netherlands.
publications@ilsieurope.be

Several groups of viruses may infect persons after ingestion and then are shed
via stool. Of these, the norovirus (NoV) and hepatitis A virus (HAV) are
currently recognised as the most important human foodborne pathogens with regard 
to the number of outbreaks and people affected in the Western world. NoV and HAV 
are highly infectious and may lead to widespread outbreaks. The clinical
manifestation of NoV infection, however, is relatively mild. Asymptomatic
infections are common and may contribute to the spread of the infection.
Introduction of NoV in a community or population (a seeding event) may be
followed by additional spread because of the highly infectious nature of NoV,
resulting in a great number of secondary infections (50% of contacts). Hepatitis 
A is an increasing problem because of the decrease in immunity of populations in 
countries with high standards of hygiene. Molecular-based methods can detect
viruses in shellfish but are not yet available for other foods. The applicability
of the methods currently available for monitoring foods for viral contamination
is unknown. No consistent correlation has been found between the presence of
indicator microorganisms (i.e. bacteriophages, E. coli) and viruses. NoV and HAV 
are highly infectious and exhibit variable levels of resistance to heat and
disinfection agents. However, they are both inactivated at 100 degrees C. No
validated model virus or model system is available for studies of inactivation of
NoV, although investigations could make use of structurally similar viruses (i.e.
canine and feline caliciviruses). In the absence of a model virus or model
system, food safety guidelines need to be based on studies that have been
performed with the most resistant enteric RNA viruses (i.e. HAV, for which a
model system does exist) and also with bacteriophages (for water). Most
documented foodborne viral outbreaks can be traced to food that has been manually
handled by an infected foodhandler, rather than to industrially processed foods. 
The viral contamination of food can occur anywhere in the process from farm to
fork, but most foodborne viral infections can be traced back to infected persons 
who handle food that is not heated or otherwise treated afterwards. Therefore,
emphasis should be on stringent personal hygiene during preparation. If viruses
are present in food preprocessing, residual viral infectivity may be present
after some industrial processes. Therefore, it is key that sufficient attention
be given to good agriculture practice (GAP) and good manufacturing practice (GMP)
to avoid introduction of viruses onto the raw material and into the
food-manufacturing environment, and to HACCP to assure adequate management of
(control over) viruses present during the manufacturing process. If viruses are
present in foods after processing, they remain infectious in most circumstances
and in most foods for several days or weeks, especially if kept cooled (at 4
degrees C). Therefore, emphasis should be on stringent personal hygiene during
preparation. For the control of foodborne viral infections, it is necessary to:
Heighten awareness about the presence and spread of these viruses by
foodhandlers; Optimise and standardise methods for the detection of foodborne
viruses; Develop laboratory-based surveillance to detect large, common-source
outbreaks at an early stage; and Emphasise consideration of viruses in setting up
food safety quality control and management systems (GHP, GMP, HACCP).

Publication Types: 
    Review

PMID: 14672828 [PubMed - indexed for MEDLINE]

440: World J Gastroenterol. 2003 Dec;9(12):2698-700.

N-acetyl cysteine therapy in acute viral hepatitis.

Gunduz H, Karabay O, Tamer A, Ozaras R, Mert A, Tabak OF.

Department of Internal Medicine and Cordiology, Izzet Baysal Medical Faculty,
Izzet Baysal University/Bolu, Turkey. drhuseyingunduz@yahoo.com

AIM: To investigate the effect of N-acetyl cysteine (NAC) on acute viral
hepatitis (AVH). METHODS: We administered 200 mg oral NAC three times daily (600 
mg/day) to the study group and placebo capsules to the control group. All
patients were hospitalized and diagnosed as AVH. Blood total and direct
bilirubin, ALT, AST, alkaline phosphatase, albumin and globulin levels of each
patient were measured twice weekly until total bilirubin level dropped under 2
mg/dl, ALT level under 100 U/L, follow up was continued and then the patients
were discharged. RESULTS: A total of 41(13 female and 28 male) AVH patients were 
included in our study. The period for normalization of ALT and total bilirubin in
the study group was 19.7+/-6.9 days and 13.7 +/- 8.5 days respectively. In the
control group it was 20.4 +/- 6.5 days and 16.9 +/- 7.8 days respectively
(P>0.05). CONCLUSION: NAC administration effected neither the time necessary for 
normalization of ALT and total bilirubin values nor duration of hospitalization, 
so we could not suggest NAC for the treatment of icteric AVH cases. However, our 
results have shown that this drug is not harmful to patients with AVH.

Publication Types: 
    Clinical Trial
    Comparative Study
    Controlled Clinical Trial

PMID: 14669316 [PubMed - indexed for MEDLINE]

441: Indian J Gastroenterol. 2003 Sep-Oct;22(5):192-3.

Thrombocytopenic purpura as initial presentation of acute hepatitis A.

Scott JX, Gnananayagam EJ, Gupta S, Simon A, Mukhopadhya A.

Department of Child Health-Unit I, Christian Medical College, Vellore 632 004.

Extrahepatic immune manifestations are rare in hepatitis A virus infection. We
report a 4 1/2-year-old girl who presented with thrombocytopenic purpura as
initial manifestation of hepatitis A virus infection. She responded to steroid
therapy.

Publication Types: 
    Case Reports

PMID: 14658540 [PubMed - indexed for MEDLINE]

442: Turk J Gastroenterol. 2003 Sep;14(3):204-7.

A case of autoimmune hepatitis and autoimmune hemolytic anemia following
hepatitis A infection.

Urganci N, Akyildiz B, Yildirmak Y, Ozbay G.

Clinic of Pediatrics, Sişli Etfal Hospital, Istanbul, Turkey.
aurganci@netas.com.tr

Hepatitis A infection is known to induce autoimmune hepatitis and autoimmune
hemolytic anemia. Here we present a case with autoimmune hepatitis type I and
autoimmune hemolytic anemia following hepatitis A virus (HAV) infection. Case:
M.A., a male patient, was brought to the hospital with complaints of jaundice and
malaise. Physical examination revealed paleness and icterus. The liver was
palpable 5 cm below the costal margin in the midclavicular line; the spleen was
palpable 2 cm from the costal margin. Laboratory examination revealed severe
anemia, reticulocytosis and direct Coombs' IgG positivity. Liver enzymes, total
and conjugated bilirubin and alkaline phosphates levels, total protein and
immunglobulin levels were high and prothrombin time elongated. Hepatitis A IgM
antibody was found positive, while other hepatitis serologic markers were
negative. Anti-smooth muscle antibody (ASMA) was positive in 1/80 titer. With
these laboratory findings, the case was diagnosed as autoimmune hepatitis and
autoimmune hemolytic anemia induced by hepatitis A infection. Liver histology
also supported the diagnosis. Steroid therapy resulted in clinical and laboratory
remission. In conclusion, it is important to vaccinate children against hepatitis
A infection to protect them from its complications and also from autoimmune
diseases induced by this infection.

Publication Types: 
    Case Reports

PMID: 14655068 [PubMed - indexed for MEDLINE]

443: MMWR Morb Mortal Wkly Rep. 2003 Nov 28;52(47):1155-7.

Comment in:
    Ann Emerg Med. 2004 May;43(5):660-2; discussion 662-3.

Hepatitis A outbreak associated with green onions at a restaurant--Monaca,
Pennsylvania, 2003.

Centers for Disease Control and Prevention (CDC).

The Pennsylvania Department of Health and CDC are investigating an outbreak of
hepatitis A outbreak among patrons of a restaurant (Restaurant A) in Monaca,
Pennsylvania. As of November 20, approximately 555 persons with hepatitis A have 
been identified, including at least 13 Restaurant A food service workers and 75
residents of six other states who dined at Restaurant A. Three persons have died.
Preliminary sequence analysis of a 340 nucleotide region of viral RNA obtained
from three patrons who had hepatitis A indicated that all three virus sequences
were identical. Preliminary analysis of a case-control study implicated green
onions as the source of the outbreak.

PMID: 14647018 [PubMed - indexed for MEDLINE]

444: J Med Virol. 2004 Jan;72(1):10-6.

Time course of hepatitis A viremia and viral load in the blood of human hepatitis
A patients.

Normann A, Jung C, Vallbracht A, Flehmig B.

Klinik für Kinderheilkunde und Jugendmedizin, Universität Tübingen, Tübingen,
Germany.

The hepatitis A virus (HAV) is the most common etiological cause of acute
hepatitis infections in humans in industrialized countries. Investigations into
the viral load during HAV viremia, however, are rare. Therefore, correlation
studies between viral load, biochemical, and specific serological markers have
been undertaken. The group of sera comprised a series of multiple consecutive
blood samples drawn from 11 patients at different times after onset of the
disease. During the period up to 70 days after the onset of icterus, the
individual range was at 1 x 10(3) to 3 x 10(4) HAV genome equivalents/ml. From
day 75 until 120 after onset of the disease, the levels traced were at 10(3). In 
one case, it was possible to trace 1.25 x 10(4) genome equivalents/ml up to 180
days after onset of icterus and in two cases even up to 408 and 490 days viral
load levels of 5 x 10(3) and 4 x 10(4) were detected, respectively. The same sera
were used to measure IgM class antibodies to hepatitis A virus and the total
anti-HAV. The results demonstrate that a direct correlation to peak levels of
viral load exists with peak serum transaminase levels, but neither with peak
anti-HAV IgM levels nor with total anti-HAV. Decreasing amounts of anti-HAV IgM
tend to occur with decreasing amounts of HAV genome equivalents; and, vice versa,
increasing amounts of total anti-HAV are accompanied by decreasing amounts of HAV
genome equivalents. The longest duration of viremia was found in patients
infected with HAV genotype IA. Copyright 2004 Wiley-Liss, Inc.

PMID: 14635005 [PubMed - indexed for MEDLINE]

445: Int J Hyg Environ Health. 2003 Oct;206(6):575-82.

The relation between anti-hepatitis A virus antibodies and residence water access
in Rio de Janeiro, Brazil.

Luiz RR, Almeida RM, Almeida RT, de Almeida LM.

Institute for Public Health Studies, Federal University of Rio de Janeiro, Rio de
Janeiro, Brazil. ronir@acd.ufrj.br

OBJECTIVES: The objective of this study was to analyse the relation between
residence water access (water taps) and hepatitis A virus (HAV) antibodies,
associated with socio-economic, environmental and demographic factors. METHODS: A
logistic regression model was used for estimating the relation between
residential water access (presence of water taps inside the house) and HAV
antibodies, related to confounding effects of selected variables. The odds ratios
estimated by the model were used as incidence density ratios (IDR) for the
analysis of the water access-antibody association. Data were obtained from a
cross-sectional study on the seroprevalence of hepatitis A in 3779 volunteers
from Duque de Caxias city, greater Rio de Janeiro, Brazil. Participants were
selected according to an age-specified random sampling survey. RESULTS: Besides
water access (main variable of interest), age, monthly family income, housewife
schooling, persons per room, proximity to open sewage channels and consumption
water treatment were statistically associated to hepatitis A seroprevalences. An 
interaction between water access and proximity to open sewage channels was
detected. Persons living in residences distant from an open sewage channel had a 
water access-antibody IDR of 2.5 (95% CI [1.4; 4.3]), in contrast to 1.1 for
those living close to such channels. CONCLUSIONS: Although indirectly measured
through the proxy variable water access, personal hygiene, in conjunction with
the absence of open sewage channels in the proximity of the residence, was an
important factor for low HAV seroprevalence study population.

PMID: 14626904 [PubMed - indexed for MEDLINE]

446: Acta Gastroenterol Belg. 2003 Jul-Sep;66(3):250-4.

Postexposure management of hepatitis A, B or C: treatment, postexposure
prophylaxis and recommendations.

Delwaide J.

Service de gastroentérologie, CHU Sart Tilman, 4000 Liège.
jean.delwaide@chu.ulg.ac.be

Although there is no consensus on the best management of acute hepatitis C or on 
optimal strategy of follow-up after potential contamination, certain guidelines
can nevertheless be proposed for the care of these patients in practice. It is
now recommended that acute hepatitis C be treated by interferon monotherapy in
the presence of a C viremia, detectable by polymerase chain reaction, and an
elevation of the transaminases. The earlier the treatment is started after
appearance of symptoms, the more effective it is. Management of a potentially
contaminated individuals consists of screening for the C virus as early as the
fifteenth day after the potentially contaminating act and, in the case of virus
transmission, starting interferon treatment as soon as elevation of the
transaminases appears. No special precautions are to be taken by the person
potentially contaminated for avoiding possible secondary C virus transmission
during the follow-up period. In the case of acute hepatitis B, antiviral
treatment should not be started, in view of the high percentage of spontaneous
recoveries and the potentially negative effect of treatment on the chances of
spontaneous recovery. Post-exposure prophylaxis by anti-hepatitis B immunoglobin 
injections and/or vaccination should be considered after evaluation of the
hepatitis B surface antigen status of the source and of the vaccination and
vaccine-response status of the exposed person. The classic scheme for selecting
the most appropriate postexposure prophylaxis is reminded. In post-exposure
prophylaxis for hepatitis A virus, although there have been no studies comparing 
the effectiveness of vaccination with that of immunoglobin injections, it is at
present proposed to provide only vaccination. The target groups eligible for
post-exposure prophylaxis are evoked.

PMID: 14618959 [PubMed - indexed for MEDLINE]

447: Hepatobiliary Pancreat Dis Int. 2002 Feb;1(1):83-6.

Detection of anti-MHAV and anti-MHEV IgM in patients with sporadic acute
hepatitis in Beijing between 1995-2000.

Lu J, Zhao HL, Meng QL, Liao SD, Wang Y, Jiang YZ.

Laboratory of Hepatitis, Institute of Virology, Chinese Academy of Preventive
Medicine, Beijing 100052, China. jlu@btamial.net.cn

OBJECTIVE: To investigate the age range, liver function damage and prognosis of
patients with sporadic acute hepatitis A and E in Beijing. METHODS: Enzyme
immunoassay (EIA) was used to detect anti-HAV and anti-HEV immunoglobulin M
(IgM). Serum samples were collected from the patients with sporadic acute viral
hepatitis in Beijing from January 1995 to June 2000. RESULTS: The total Positive 
rate for anti-HAV and anti-HEV IgM was 55.2% (112) in 203 patients with acute
hepatitis, of whom 22.2% (45 patients) and 33.0% (67) were positive for anti-HAV 
and anti-HEV respectively. The duration of anti-HEV IgM was 45-60 days and that
of anti-HAV IgM was at least 2-3 months. The patients with acute hepatitis A and 
hepatitis E all experienced jaundice and a rising of liver enzyme, but did not
develop chronic hepatitis or died. CONCLUSION: Acute hepatitis A as well as acute
hepatitis E plays an important role in sporadic enterically transmitted hepatitis
in Beijing.

PMID: 14607630 [PubMed - indexed for MEDLINE]

448: Clin Ther. 2003 Sep;25(9):2337-51.

A review of combined hepatitis A and hepatitis B vaccination for travelers.

Spira AM.

The Travel Medicine Center, Beverly Hills, California 90211, USA.
travelmed@earthlink.net

BACKGROUND: Hepatitis A virus (HAV) and hepatitis B virus (HBV) are the 2 most
common vaccine-preventable diseases for which travelers are at risk. These
viruses are a significant public health concern, as both HAV and HBV cause
substantial morbidity and both can be fatal. OBJECTIVE: This article provides the
practitioner with the facts about hepatitis and travel, including why travelers
are at risk, which travelers are at greatest risk, and how travelers can protect 
themselves from both HAV and HBV through vaccination. METHODS: A review of the
English-language literature published from 1966 to 2002 was conducted through the
PreMedline and MEDLINE databases with the search terms hepatitis A, hepatitis B, 
and travelers. Reference lists from relevant articles were also searched, and
abstracts presented at recent conferences were evaluated. Articles containing
information from the past 2 decades were used to reference this article. RESULTS:
Travelers need protection against both hepatitis A and B. In addition to making
travelers aware of a number of behavior modifications, vaccination should be
provided. Tolerable and effective monovalent vaccines are available that can
prevent these viruses. In addition, a combination HAV/HBV vaccine is available
that is well tolerated and decreases the time to immunity. CONCLUSIONS: Travelers
are often unaware of the risk factors for acquiring hepatitis A and B while
traveling, such as the degree of endemicity at the travel destination, the length
of stay in the endemic area, and the extent and frequency of contact with the
local population. Because these risk factors and areas for endemicity of both
hepatitis A and hepatitis B overlap, health care providers can protect travelers 
from both of these diseases by providing a combination vaccine, thus affording a 
lifetime of protection against both diseases.

Publication Types: 
    Review

PMID: 14604737 [PubMed - indexed for MEDLINE]

449: Sex Transm Dis. 2003 Nov;30(11):859-65.

Comment in:
    Sex Transm Dis. 2005 Aug;32(8):465.

Cost-effectiveness of hepatitis A/B vaccine versus hepatitis B vaccine in public 
sexually transmitted disease clinics.

Jacobs RJ, Meyerhoff AS.

Capitol Outcomes Research, Inc, Alexandria, VA 22310, USA.
jake.jacobs@capitaloutcomesresearch.com

BACKGROUND: Many patients seen at U.S. sexually transmitted disease (STD) clinics
are offered hepatitis B vaccination. Substituting hepatitis A/B vaccine would
provide additional protection but increase costs. GOAL: The goal was to estimate 
the cost effectiveness of hepatitis A/B versus B vaccination for 1,000,000 public
STD clinic attenders. STUDY DESIGN: A Markov model of hepatitis A outcomes was
developed using published literature, U.S. government databases, and expert panel
opinion. Added vaccination costs were compared with savings from reduced
hepatitis A treatment. Net costs were compared with life-years saved and
quality-adjusted life-years (QALYs) gained. RESULTS: Substituting hepatitis A/B
vaccine would prevent 2263 overt hepatitis A infections, 292 hospitalizations, 8 
premature deaths, and the loss of 281 QALYs. Net health system costs would be
$20,892 per life-year saved, or $13,397 per QALY gained. CONCLUSION: Substituting
hepatitis A/B for hepatitis B vaccine would reduce morbidity and mortality in a
cost-effective manner.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 14603096 [PubMed - indexed for MEDLINE]

450: Virology. 2003 Oct 10;315(1):34-42.

Evidence for quasispecies distributions in the human hepatitis A virus genome.

Sánchez G, Bosch A, Gómez-Mariano G, Domingo E, Pintó RM.

Grup Virus Entèrics, Department of Microbiology, University of Barcelona, 08028
Barcelona, Spain.

Nucleotide sequence analysis of multiple molecular clones of the hepatitis A
virus (HAV), generated by reverse transcription-PCR of two capsid-coding regions,
revealed a degree of heterogeneity compatible with a quasispecies structure in
three clinical samples. Passage of plaque-purified reference strain HAV pHM175
43c in FRhK-4 cells documented the generation of a mutant distribution of HAV
genomes. The mutant spectra showed mutation frequencies in the range of 1 x
10(-3) to 1 x 10(-4) substitutions per nucleotide, with a dominance of transition
over transversion mutations. While in the VP3-coding region, nonsynonymous
mutations were predominant; in the VP1-coding region they were uncommon. Around
50% of the amino acid replacements involved residues located at or near antigenic
sites. Most of the detected mutations occurred at or in the vicinity of rare
codons, suggesting a dynamics of mutation-selection, predominantly at and around 
rare codons. The results indicate that despite antigenic conservation, HAV
replicates as a complex distribution of mutants, a feature of viral quasispecies.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 14592757 [PubMed - indexed for MEDLINE]

451: Vaccine. 2003 Dec 1;21(32):4650-4.

A combined dual-chamber typhoid/hepatitis A vaccine as a booster dose in
hepatitis A primed adults.

Beran J, Chlibek R, Weber F.

Vaccination and Travel Medicine Centre, Poliklinika II, Bratri Stefanu 895, 50003
Hradec Králové, Czech Republic. jiri.beran@vakcinace.cz

Vivaxim is a combined hepatitis A/typhoid fever vaccine (HA/Vi) licensed for
vaccination of travellers, but long-term protection against hepatitis A requires 
two immunisations at least 6 months apart. A randomised, controlled study was
performed in 116 healthy adults primed with hepatitis A vaccine (Avaxim) to
compare immune responses to HA/Vi and Avaxim given as booster doses 6 months
later. Both vaccines elicited marked booster responses achieving antibody
geometric mean titres (GMTs) of 4576 and 3760 mIU/ml in the HA/Vi and Avaxim
groups, respectively. Although twice as frequent in the HA/Vi group, local
reactions (mostly pain) were mainly mild and transient, probably reflecting the
larger volume injected (1ml). Vivaxim offers a convenient means of administering 
both HA and typhoid fever vaccines in subjects already primed for hepatitis A.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 14585671 [PubMed - indexed for MEDLINE]

452: Yonsei Med J. 2003 Oct 30;44(5):939-42.

An unusual combination of relapsing and cholestatic hepatitis A in childhood.

Ertekin V, Selimoğlu MA, Orbak Z.

Department of Pediatrics, Atatürk University, School of Medicine, Erzurum,
Turkey. vdinar@turk.net

Clinical variants of hepatitis A include the prolonged, relapsing and cholestatic
forms. Here, the first childhood case of hepatitis A, with a combination of the
relapsing and cholestatic forms is presented, a 14-year old boy. In the first
phase of the illness, while the AST and ALT levels were declined, th total and
direct bilirubin and GGT were increased. The patient was thought to have the
cholestatic form of hepatitis A. Du to intense pruritus and high bilirubin
levels, ursodeoxycholic acid (UDCA) therapy was started. On the 17th day, the
decreased AST and ALT levels began to increase, reaching levels as high as 484
U/L and 862 U/L, respectively. The UDCA treatment was stopped on the 64th day. On
the 164th day, all his laboratory parameters were within normal limits, but the
anti-HAV IgM was still positive.

Publication Types: 
    Case Reports

PMID: 14584117 [PubMed - indexed for MEDLINE]

453: Am J Prev Med. 2003 Nov;25(4):343-6.

Costs of a hepatitis A outbreak affecting homosexual men: Franklin County, Ohio, 
1999.

Sansom SL, Cotter SM, Smith F, Koch E, de Fijter S, Long T, Coleman D, Cowen K,
Tilgner S, Pry N, Bell BP.

National Immunization Program, Centers for Disease Control and Prevention, 1600
Clifton Road, MS E-45, Atlanta, GA 30333, USA. ssansom@cdc.gov

BACKGROUND: Hepatitis A is one of the most commonly reported, vaccine-preventable
diseases in the United States. Many cases occur in association with
community-wide outbreaks, but societal costs to the community are seldom
documented. METHODS: Hepatitis A case-patients available for a follow-up
interview as part of an outbreak investigation were asked about hospitalization, 
healthcare costs, missed work, and lost wages associated with their illness, as
well as healthcare insurance coverage and sick-leave reimbursement. Average costs
were calculated by case-patient age, gender, and hospitalization status for lost 
wages, and by age and hospitalization status for medical costs, and then assigned
to case-patients not re-interviewed to provide an estimate of overall costs.
Health departments provided outbreak-associated costs. RESULTS: Between the weeks
of November 2, 1998, and May 17, 1999, a total of 136 cases of hepatitis A were
reported. Of the 89 (65.4%) case-patients available for interview, 74 (83%) were 
male; of those, 47 (64%) identified themselves as men who have sex with men
(MSM). The average cost of the outbreak per case-patient was $2894 US dollars, of
which 51% was associated with lost wages, 40% with medical costs, and 9% with
health department costs. Case-patients incurred 44% of total outbreak costs;
employers, 29%; healthcare insurers, 18%; and health departments, 9%.
CONCLUSIONS: In this community-wide hepatitis A outbreak, case-patients incurred 
the largest portion of costs, followed by employers, healthcare insurers, and
health departments.

Publication Types: 
    Research Support, U.S. Gov't, P.H.S.

PMID: 14580638 [PubMed - indexed for MEDLINE]

454: Can J Gastroenterol. 2003 Oct;17(10):593-6.

Viral hepatitis in a Canadian First Nations community.

Minuk GY, Zhang M, Wong SG, Uhanova J, Bernstein CN, Martin B, Dawood MR, Vardy
L, Giulvi A.

Department of Medicine, University of Manitoba, Winnipeg. gminuk@cc.umanitoba.ca

Serological markers for hepatitis A (HAV), B (HBV) and C (HCV) were documented in
315 inhabitants (27%) of a central Manitoba First Nations community. Serologic
evidence of HAV infection (anti-HAV positive) was almost universal (92%) by the
age of 20 years. HBV infection (antibody to hepatitis B core antigen positive)
had occurred in only 2.3% of the study population and no chronic carriers were
identified. Serological evidence of HCV infection (anti-HCV positive) was
documented in 2.2% of the population but ongoing viremia (HCV-RNA positive by
polymerase chain reaction) was absent. The results of this study highlight the
importance of universal HAV vaccination; likely reflect the efficacy of existing 
prenatal screening and immunoprophylaxis programs for HBV; and raise the
possibility that First Nations peoples have an enhanced ability to spontaneously 
clear HCV.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 14571297 [PubMed - indexed for MEDLINE]

455: Med J Malaysia. 2002 Mar;57(1):70-9.

Comment in:
    Med J Malaysia. 2002 Mar;57(1):1-2.

Review of the trends and causes of food borne outbreaks in Malaysia from 1988 to 
1997.

Meftahuddin T.

Disease Control Division, Department of Public Health, Ministry of Health, Kuala 
Lumpur.

This paper examines the trend and possible contributing factors for the
occurrence of the food borne diseases outbreaks in Malaysia. These diseases
mainly are cholera, typhoid fever, hepatitis A, dysentery and food poisoning. The
outbreaks still occur sporadically in certain high risk areas throughout the
country. The incidence rate of all the other three major food borne diseases
steadily declined from the year 1988 to 1997 except for food poisoning and
cholera. Statistic of food poisoning from the year 1996 to 1997 showed that 66.5%
of the outbreak occurred in schools whereas only 0.4% originated from the
contaminated food sold at various public food outlets. The school age group is
always more affected than the general population. Amongst the contributing
factors identified are related to unhygienic food handling practices followed by 
inadequate safe water supply and poor environmental sanitation. A multisectoral
approach between Ministry of Health and other government agencies or private
agents needs to be undertaken in the management of the food borne diseases in
order to curb the incidences of food borne diseases in Malaysia.

PMID: 14569721 [PubMed - indexed for MEDLINE]

456: Public Health Rep. 2003 Nov-Dec;118(6):550-8.

An economic assessment of pre-vaccination screening for hepatitis A and B.

Jacobs RJ, Saab S, Meyerhoff AS, Koff RS.

Capitol Outcomes Research, Inc., Alexandria, VA 22310, USA.
jake.jacobs@capitoloutcomesresearch.com

OBJECTIVE: The availability of a single vaccine active against hepatitis A and B 
may facilitate prevention of both infections, but complicates the question of
whether to conduct pre-vaccination screening. The authors examined the
cost-effectiveness of pre-vaccination screening for several populations:
first-year college students, military recruits, travelers to hepatitis A-endemic 
areas, patients at sexually transmitted disease clinics, and prison inmates.
METHODS: Three prevention protocols were examined: (1) screen and defer
vaccination until serology results are known; (2) screen and begin vaccination
immediately to avoid a missed vaccination opportunity; and (3) vaccinate without 
screening. Data describing pre-vaccination immunity, vaccine effectiveness, and
prevention costs borne by the health system (i.e., serology, vaccine acquisition,
and administration) were derived from published literature and U.S. government
websites. Using spreadsheet models, the authors calculated the ratio of
prevention costs to the number of vaccine protections conferred. RESULTS: The
vaccinate without screening protocol was most cost-effective in nine of 10
analyses conducted under baseline assumptions, and in 69 of 80 sensitivity
analyses. In each population considered, vaccinate without screening was less
costly than and at least equally as effective as screen and begin vaccination.
The screen and defer vaccination protocol would reduce costs in seven
populations, but effectiveness would also be lower. CONCLUSIONS: Unless directed 
at vaccination candidates with the highest probability of immunity,
pre-vaccination screening for hepatitis A and B immunity is not cost-effective.
Balancing cost reduction with reduced effectiveness, screen and defer may be
preferred for older travelers and prison inmates.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 14563912 [PubMed - indexed for MEDLINE]

457: Z Gastroenterol. 2003 Oct;41(10):983-90.

Immunogenicity of an accelerated vaccination regime with a combined hepatitis a/b
vaccine in patients with chronic hepatitis C.

Kallinowski B, Jilg W, Buchholz L, Stremmel W, Engler S.

Department of Internal Medicine IV, University of Heidelberg, Heidelberg,
Germany. birgit_kalinowski@med.uni-heidelberg.de

OBJECTIVES: Hepatitis A (HAV) and B (HBV) vaccinations are recommended in
patients with chronic liver diseases. METHODS: We prospectively investigated
immunogenicity and safety of an accelerated vaccination protocol (0-7-21 days)
with the combined hepatitis A/B vaccine (Twinrix(R)) versus the standard
vaccination scheme (0-1-6 months) in hepatitis C virus-infected patients versus
healthy volunteers. RESULTS: Local and general symptoms were mostly mild in all
groups. One month after completion of the accelerated vaccination or standard
vaccination, with the combined hepatitis A/B vaccine anti-HAV seroconversion
rates (>33 IU/l) were 89 % and 88 % in HCV-infected patients. Initial
HCV-nonresponders developed protective anti-HAV antibodies in 94 % and 96 % after
a booster dose. According to the anti-HBs seroprotection rate, HCV-infected
patients developed protective anti-HBs titres (>10 IU/l) in 77 % and 82 % of
cases one month after the accelerated and the standard vaccination scheme-at
month 2 and 7, respectively. This anti-HBs seroprotection rate could even be
increased to 84 % and 85 % when initial HCV-infected nonresponders where given a 
booster dose with the combined hepatitis A/B vaccine. Protective anti-HAV and
anti-HBs titers were achieved as early as month 2 after the accelerated
vaccination schedule in the majority of HCV-infected patients. Healthy subjects
developed protective anti-HAV titers and anti-HBs titers in 100 % and 98 % after 
the accelerated and standard vaccination protocol. CONCLUSIONS: This study is the
first to have demonstrated that the accelerated combined hepatitis A/B
vaccination is both safe and highly immunogenic against HAV and HBV in
HCV-infected patients with well compensated liver disease.

Publication Types: 
    Clinical Trial
    Comparative Study
    Controlled Clinical Trial

PMID: 14562195 [PubMed - indexed for MEDLINE]

458: Clin Infect Dis. 2003 Nov 1;37(9):e126-8. Epub 2003 Sep 30.

Successful booster antibody response up to 54 months after single primary
vaccination with virosome-formulated, aluminum-free hepatitis A vaccine.

Beck BR, Hatz C, Brönnimann R, Herzog C.

Swiss Tropical Institute, Basel, Switzerland. bernhard.beck@unibas.ch

This study demonstrates that a booster dose of the virosome-formulated,
aluminum-free hepatitis A vaccine Epaxal (Berna Biotech) is highly immunogenic in
subjects who received a single primary dose of this vaccine 18-54 months earlier.
There were no significant differences in geometric mean antibody titers (GMTs)
among subjects who received the booster dose 18-29 months (GMT, 2330 mIU/mL),
30-41 months (GMT, 2395 mIU/mL), or 42-54 months (GMT, 2432 mIU/mL) after primary
vaccination, indicating that delays in the administration of booster vaccination 
do not lead to a loss of immunogenicity.

Publication Types: 
    Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 14557982 [PubMed - indexed for MEDLINE]

459: Pediatr Infect Dis J. 2003 Oct;22(10):904-14.

Regional variation in the cost effectiveness of childhood hepatitis A
immunization.

Jacobs RJ, Greenberg DP, Koff RS, Saab S, Meyerhoff AS.

Capitol Outcomes Research, Inc, Alexandria, VA 22310, USA.
Jake.Jacobs@CapitolOutcomesResearch.com

BACKGROUND: Routine childhood hepatitis A immunization is recommended in regions 
with incidence rates twice the national average, but it may be cost-effective in 
a wider geographic area. OBJECTIVE: To evaluate the costs and benefits of
potential hepatitis A immunization of healthy US children in regions with varying
hepatitis A incidences. METHODS: We considered vaccination of the 2000 US birth
cohort in states defined by historic hepatitis A incidence rates. Infections
among potential vaccinees and their personal contacts were predicted from age 2
through 85 years. Net vaccination costs were estimated from health system and
societal perspectives and were compared with life-years saved and
quality-adjusted life years (QALYs) gained using a 3% discount rate.RESULTS
Nationally vaccination would prevent >75 000 cases of overt hepatitis A disease. 
Approximately two-thirds of health benefits would accrue to personal contacts
rather than to vaccinees themselves. In states with incidence rates of > or
=200%, 100 to 199%, 50 to 99% and <50% the national average, societal costs per
QALY gained would be <0, <0, 13,800 and 63,000 US dollars, respectively.
Nationally vaccination would cost 9100 US dollars per QALY gained from the
perspective of the health system and 1400 US dollars per QALY gained from
society's perspective. Results are most sensitive to vaccination costs and rates 
of disease transmission through personal contact. CONCLUSION: Childhood hepatitis
A vaccination is most cost-effective in areas with the highest incidence rates
but would also meet accepted standards of economic efficiency in most of the US. 
A national immunization policy would prevent substantial morbidity and mortality,
with cost effectiveness similar to that of other childhood immunizations.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 14551492 [PubMed - indexed for MEDLINE]

460: J Community Health. 2003 Oct;28(5):347-62.

Using an integrated approach to understand vaccination behavior among young men
who have sex with men: stages of change, the health belief model, and
self-efficacy.

Rhodes SD, Hergenrather KC.

Section on Social Sciences and Health Policy, Department of Public Health
Sciences, Wake Forest University School of Medicine, Winston-Salem, NC
27157-1063, USA. srhodes@wfubmc.edu

Studies continue to show that the majority of men who have sex with men (MSM) in 
the United States remain unvaccinated against hepatitis A (HAV); such limited
vaccination coverage is a missed opportunity for preventing disease. This study
sought to identify beliefs and attitudes associated with motivational readiness
for vaccination against HAV among MSM, using a theoretically-integrated
framework. Questionnaire data were collected from 358 MSM through bar outreach.
MSM with increased readiness to complete the two-dose series perceived lower
practical barriers and reported greater healthcare provider communication about
their sexual orientation and risk behavior. They also perceived higher benefits
to vaccination and higher severity of infection, and had higher self-efficacy to 
complete the vaccine series. Relationships between stages of change and
theory-based constructs from the health belief model and the social learning
theory follow predicted patterns suggesting that these theories may provide
useful frameworks for understanding vaccination readiness and intervention
strategy development among MSM.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 14535600 [PubMed - indexed for MEDLINE]

461: Clin Infect Dis. 2003 Oct 15;37(8):1067-72. Epub 2003 Sep 23.

Seroepidemiology of Helicobacter pylori and hepatitis A virus and the mode of
transmission of infection: a 9-year cohort study in rural Japan.

Malaty HM, Tanaka E, Kumagai T, Ota H, Kiyosawa K, Graham DY, Katsuyama T.

Department of Medicine, Veterans Affair Medical Center and Baylor College of
Medicine, Houston, Texas 77030, USA. Hmalaty@bcm.tmc.edu

We compared the seroepidemiologic patterns of Helicobacter pylori and hepatitis A
virus (HAV) infections among participants in 2 independent cross-sectional
studies conducted in Japan in 1986 and 1994. Subgroups were monitored with
successive blood sampling. H. pylori and HAV infection status was defined by
results of enzyme-linked immunosorbent assay. In 1986, the prevalence of H.
pylori infection and HAV infection, respectively, were 80% and 70% among adults
and 31% and 5% among children. The prevalence of both infections increased with
age. Concordant infections were found in 74.5% of adults (kappa=0.2) versus 2% of
children (kappa=0.05). During the 9-year study period, the incidence of H. pylori
infection was 1.1% among adults and 2% among children. The seroprevalence of HAV 
remained constant. The disparity between the increase in prevalence of H. pylori 
and HAV infection with age is likely associated with improvements in hygienic
practices. The discordance between the presence of the infections among younger
persons is evidence against a common source and/or vehicle for transmission.

PMID: 14523771 [PubMed - indexed for MEDLINE]

462: Lancet. 2003 Sep 27;362(9389):1065-71.

Hepatitis A booster vaccination: is there a need?

Van Damme P, Banatvala J, Fay O, Iwarson S, McMahon B, Van Herck K, Shouval D,
Bonanni P, Connor B, Cooksley G, Leroux-Roels G, Von Sonnenburg F; International 
Consensus Group on Hepatitis A Virus Immunity.

Centre for the Evaluation of Vaccination, WHO Collaborating Centre for Control
and Prevention of Viral Hepatitis, Unit of Epidemiology and Social Medicine,
University of Antwerp, 2610 , Antwerp, Belgium. pierre.vandamme@ua.ac.be

Hepatitis A is one of the most common vaccine-preventable infectious diseases in 
the world. Effective vaccines against hepatitis A have been available since 1992,
and they provide long-term immunity against the infection. However, there is no
worldwide consensus on how long protection will last or whether there will be a
need for hepatitis A virus (HAV) booster vaccinations in the future. In most
countries, booster-vaccination policy is guided by manufacturers'
recommendations, national authorities, or both. In June, 2002, a panel of
international experts met to review the long-term immunogenicity and protection
conferred by HAV vaccine in different population groups. Data have shown that
after a full primary vaccination course, protective antibody amounts persist
beyond 10 years in healthy individuals, and underlying immune memory provides
protection far beyond the duration of anti-HAV antibodies. The group concluded
that there is no evidence to lend support to HAV booster vaccination after a full
primary vaccination course in a healthy individual. However, further
investigations are needed before deciding if boosters can be omitted in special
patient-groups.

Publication Types: 
    Comparative Study
    Consensus Development Conference
    Research Support, Non-U.S. Gov't
    Review

PMID: 14522539 [PubMed - indexed for MEDLINE]

463: J Am Coll Health. 2003 May;51(6):227-36.

The cost effectiveness of hepatitis immunization for US college students.

Jacobs RJ, Saab S, Meyerhoff AS.

Capitol Outcomes Research, Alexandria, Virginia 22310, USA.
Jake.Jacobs@CapitolOutcomesResearch.com

Hepatitis B immunization is recommended for all American children, and hepatitis 
A immunization is recommended for children who live in areas with elevated
disease rates. Because hepatitis A and B occur most commonly in young adults, the
authors examined the cost effectiveness of college-based vaccination. They
developed epidemiologic models to consider infection risks and disease
progression and then compared the cost of vaccination with economic, longevity,
and quality of life benefits. Immunization of 100,000 students would prevent
1,403 acute cases of hepatitis A, 929 cases of hepatitis B, and 144 cases of
chronic hepatitis B. Hepatitis B vaccination would cost the health system $7,600 
per quality-adjusted life year (QALY) gained but would reduce societal costs by
6%. Hepatitis A/B vaccination would cost the health system dollar 8,500 per QALY 
but would reduce societal costs by 12%. Until childhood and adolescent
vaccination can produce immune cohorts of young adults, college-based hepatitis
immunization can reduce disease transmission in a cost-effective manner.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 14510025 [PubMed - indexed for MEDLINE]

464: Psychosom Med. 2003 Sep-Oct;65(5):831-5.

Sleep enhances the human antibody response to hepatitis A vaccination.

Lange T, Perras B, Fehm HL, Born J.

Department of Neuroendocrinology, University of Lübeck, Lübeck, Germany.

OBJECTIVE: The common belief that sleep supports immune defense has received
surprisingly little direct experimental support. The antibody response to
vaccination provides a valid tool to assess the influence of sleep on adaptive
immune functioning in humans, which is also clinically relevant. METHODS: Two
groups of healthy humans (N = 19) not previously infected with hepatitis A virus 
(HAV) were studied. On the night after primary vaccination with inactivated HAV, 
which took place at 0900 hours, one group had regular sleep. The other group
stayed awake, and did not sleep before 2100 hours the following day. HAV antibody
titers were measured repeatedly until 28 days after vaccination. Plasma hormone
concentrations and white blood cell (WBC) subset counts were determined on the
night and day after vaccination. RESULTS: Subjects who had regular sleep after
vaccination, displayed a nearly two-fold higher HAV antibody titer after 4 weeks 
than subjects staying awake on this night (p=.018). Compared with wakefulness,
sleep after vaccination distinctly increased release of several
immune-stimulating hormones including growth hormone, prolactin, and dopamine (p 
<.01). Concentrations of thyrotropin, norepinephrine, and epinephrine were
lowered by sleep (p <.02), whereas sleep only marginally influenced WBC subset
counts. CONCLUSIONS: Data suggest that sleep compared with sleep deprivation on
the night after vaccination improves the formation of antigen-specific immune
defense as reflected by antibody production in humans. Sleep presumably acts by
inducing a hormonal environment in secondary lymphoid tissues, enhancing
lymphocyte proliferation and differentiation and finally antibody synthesis.
Results underscore the importance of sleep for immunocompetence.

Publication Types: 
    Clinical Trial
    Comparative Study
    Controlled Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 14508028 [PubMed - indexed for MEDLINE]

465: Curr Opin Infect Dis. 2003 Oct;16(5):473-9.

Hepatitis B and C virus infections in the immune compromised.

Haydon GH, Mutimer DJ.

Liver Unit, Queen Elizabeth Hospital, Birmingham, B15 2TH, UK.
GeoffHay@email.msn.com

PURPOSE OF REVIEW: This review compares and contrasts the natural history and
treatment of hepatitis B and C virus infections in three principal populations of
immune compromised individuals: (1) patients co-infected with HIV; (2) patients
with liver failure secondary to hepatitis B or C virus infection who undergo
liver transplantation, and (3) patients with hepatitis B or C virus infection who
undergo anticancer chemotherapy. RECENT FINDINGS: Chronic liver disease resulting
from hepatitis B or C virus infection progresses more rapidly in patients
co-infected with HIV than in HIV negative patients. Treatment protocols for
antiviral therapy are, however, similar to those used in immunocompetent
individuals and although few long-term results are available, the efficacy of
interferon and ribavirin therapy in hepatitis C virus/HIV infection and
lamivudine in HIV/hepatitis B virus infection has been proven in the short-term. 
Perhaps the most important consideration is the timing of administering
treatments to co-infected patients. For patients with well preserved CD4 counts
and hepatitis C virus/HIV co-infection, the hepatitis infection should be treated
as early as possible to avoid drug interactions of hepatitis C virus antivirals
with antiretroviral therapy. Also, response to hepatitis C virus treatment
appears better when treatment is administered in the context of preserved immune 
function. Conversely, in hepatitis B virus/HIV co-infection, hepatitis B virus
antivirals are best administered with anti-retroviral therapy, thus preventing
the selection of HIV viral species which may be resistant to the drugs used for
hepatitis B virus. Improved graft and patient survival after liver transplant and
with anticancer chemotherapy in hepatitis B virus infected patients has been
proven using lamivudine prophylaxis. However, although therapy for hepatitis C
virus recurrence after liver transplantation would seem rational, limited success
with current treatment protocols has been achieved. SUMMARY: Although the
prognosis of hepatitis B and C virus infections in the immune compromised may be 
inferior to that of immunocompetent individuals, such patients should have full
evaluation of their viral hepatitis, and antiviral therapy should be considered.

Publication Types: 
    Review

PMID: 14502001 [PubMed - indexed for MEDLINE]

466: Trop Gastroenterol. 2003 Jan-Mar;24(1):25-6.

Severe acute pancreatitis due to hepatitis A virus infection in a patient of
acute viral hepatitis.

Khanna S, Vij JC.

Pushpawati Singhania Research Institute for Liver, Renal and Digestive Disease,
New Delhi. psri@vsnl.com

The commonest causes of acute pancreatitis are cholelithiasis and alcohol. Rare
causes include various viral infections, among which mumps is the commonest.
Hepatitis A, hepatitis B and, recently, hepatitis E have been reported to cause
acute but mild pancreatitis in patients with acute viral hepatitis. This report
describes a case of severe acute pancreatitis caused by hepatitis A.

Publication Types: 
    Case Reports

PMID: 12974211 [PubMed - indexed for MEDLINE]

467: Sex Transm Dis. 2003 Sep;30(9):685-8.

Hepatitis A and B vaccination in a sexually transmitted disease clinic for men
who have sex with men.

Sansom S, Rudy E, Strine T, Douglas W.

Epidemic Intelligence Service, Division of Applied Public Health Training,
Epidemiology Program Office, Centers for Disease Control and Prevention, Atlanta,
Georgia, USA. ssansom@cdc.gov

BACKGROUND: Sexually transmitted disease clinics can deliver hepatitis vaccines
to men who have sex with men, but have been reluctant to do so because of
perceived low vaccination completion rates. GOAL: The goal was to evaluate
hepatitis A and B vaccination eligibility, acceptance, and completion and the
effectiveness of reminder/recall in a sexually transmitted disease clinic serving
men who have sex with men. DESIGN: Clients self-reported their eligibility for
free vaccine. Consenting clients who accepted a first dose of vaccine were
systematically assigned to receive telephone reminder/recall or standard
follow-up. RESULTS: Of 1203 clients, 71.8% were eligible for both vaccines; 62.6%
of those eligible accepted both. Reminder/recall was associated with increased
receipt of the second dose of hepatitis B vaccine (86.7% versus 80.4% among
intervention and control groups, respectively), but not with completion of both
vaccine series (55.9% versus 58.8%). CONCLUSION: The majority of clients were
eligible for both hepatitis vaccines, and most eligible clients accepted a first 
dose of both vaccines. Reminder/recall, as delivered at this clinic, failed to
increase the proportion of clients who received all vaccine doses. New delivery
mechanisms should be explored.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial

PMID: 12972790 [PubMed - indexed for MEDLINE]

468: Southeast Asian J Trop Med Public Health. 2002;33 Suppl 3:145-8.

Vaccinating Thai adolescents against hepatitis A: is it cost-effective?

Soogarun S, Wiwanitkit V.

Department of Clinical Microscopy, Faculty of Allied Health Sciences,
Chulalongkorn University, Bangkok, Thailand.

Hepatitis A infection is a common disease in tropical countries, including
Thailand. Hepatitis A vaccination of children and adolescents has been
recommended by many countries. We performed a cost-benefit analysis in order to
determine the best strategy for Thailand. Three strategies were tested: a) no
intervention; b) vaccination without screening; c) vaccination after screening. A
review of the literature was performed in order to set the path probability of
each strategy. The cost of intervention of each strategy was identified; the
outcome cost was the total economic loss due to hepatitis A infection as the
result of each strategy. Benefit was the final total cost according to each
strategy (cost of intervention and economic loss due to possible hepatitis A
infection). Surprisingly, the most benefit was gained from a strategy of no
intervention. Vaccination after screening was the worst strategy. Our results
indicated that hepatitis A vaccination for Thai adolescents was not
cost-effective.

PMID: 12971496 [PubMed - indexed for MEDLINE]

469: MMWR Morb Mortal Wkly Rep. 2003 Sep 5;52(35):844-5.

Public health dispatch: multistate outbreak of hepatitis A among young adult
concert attendees--United States, 2003.

Centers for Disease Control and Prevention (CDC).

In July 2003, a cluster of hepatitis A cases was identified among young adults
who had attended outdoor concert and camping events featuring various "jam
bands." As of September 2, a total of 25 cases have been reported among residents
of nine states (Arizona, California, Colorado, Indiana, Michigan, New York,
Oregon, Tennessee, and Wisconsin). The majority of cases were among young adults 
who attended concerts during the spring and summer. The median age of infected
persons was 23 years (range: 17-44 years); 14 (56%) were male.

PMID: 12966361 [PubMed - indexed for MEDLINE]

470: J Pediatr Gastroenterol Nutr. 2003 Sep;37(3):258-61.

Immunogenicity and safety of hepatitis A vaccine in children with chronic liver
disease.

Ferreira CT, da Silveira TR, Vieira SM, Taniguchi A, Pereira-Lima J.

Hospital de Clinicas and Universidade Federal do Rio Grande do Sul, School of
Medicine, Porto Alegre, Brazil. cristina@qbnet.com.br

BACKGROUND: Acute hepatitis A superimposed on chronic liver disease has been
associated with a more severe course of disease and development of fulminant
hepatitis. The aim of this study was to evaluate the immunogenicity and safety of
an inactivated hepatitis A virus vaccine in children with chronic liver disease. 
PATIENTS AND METHODS: This was an open, prospective, and controlled trial with 89
anti-HAV negative children between 1 and 16 years of age studied at a pediatric
liver disease and transplantation referral center. Inactivated HAV vaccine
(Havrix), from GlaxoSmithKline Biologicals containing 720 Elisa units of
alum-adsorbed hepatitis A antigen per 0.5 ml dose was used. Thirty-four pediatric
patients with chronic liver disease (mean age: 7.0 +/- 4.86 years) and 55 healthy
controls (mean age: 4.8 +/- 2.7 years) received two doses of Havrix vaccine in
months zero and six. Seroconversion and anti-HAV titers expressed as geometric
mean titers (GMT) in mIU/ml were measured at months one and seven, by a modified 
Hepatitis A virus antibodies (HAVAB) assay. RESULTS: Seroconversion rates at four
weeks after primary immunization were 76% and 94% and the GMT 107.77 and 160.77
mIU/ml in the patient and control groups, respectively. One month after second
dose the seroconversion rates were 97% and 100% in the groups with GMT of 812.40 
and 2,344.90 mIU/ml. Both doses were well tolerated with no significant adverse
events observed. Local injection-site symptoms were the most common reactions
reported in both groups. CONCLUSION: Although GMTs were significantly lower in
children with chronic liver disease compared to healthy controls, the overall
seroconversion rates were not different. Hepatitis A virus vaccine was safe,
well-tolerated, and immunogenic in children with chronic liver disease.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial

PMID: 12960646 [PubMed - indexed for MEDLINE]

471: Int J Cardiol. 2003 Aug;90(2-3):175-9.

Hepatitis A IgG seropositivity and coronary atherosclerosis assessed by
angiography.

Auer J, Leitinger M, Berent R, Prammer W, Weber T, Lassnig E, Eber B.

2nd Medical Department, General Hospital Wels, Grieskirchnerstrasse 42, A-4600
Wels, Austria. johann.auer@khwels.at

BACKGROUND: Infectious agents, in particular intracellular pathogens that can
establish long-term, persistent infection, may play an important role in
atherogenesis. We tested the hypothesis that hepatitis A virus (HAV) could be
associated with significant coronary artery disease. METHODS: The possible
association between HAV infection and angiographically proven coronary artery
disease (CAD) was studied. Blood from 218 patients undergoing coronary
angiography was tested for serum IgG antibodies to HAV. RESULTS: Of the 218
patients, 178 (81.7%) had anti-HAV IgG antibodies. CAD prevalence was 66.3% in
HAV seropositive and 57.5% in HAV seronegative patients (P=0.385). In contrast,
the number of infectious pathogens to which an individual has been exposed
correlates with CAD. Four or more of the six seromarkers tested for particular
infections (HAV, Chlamydia pneumoniae, Helicobacter pylori, cytomegalovirus,
influenza type A and type B) were positive in 48.8% of patients with CAD and in
31.2% of patients in patients without CAD (P=0.02). CONCLUSIONS: This analysis
demonstrated that HAV seropositivity is not a predictor of risk for CAD. HAV
infection, therefore, seems not to be associated with CAD. The number of
infectious agents to which an individual has been exposed ('infectious burden')
correlates with CAD.

PMID: 12957749 [PubMed - indexed for MEDLINE]

472: Epidemiol Infect. 2003 Aug;131(1):745-51.

An outbreak of hepatitis A associated with consumption of raw blueberries.

Calder L, Simmons G, Thornley C, Taylor P, Pritchard K, Greening G, Bishop J.

Public Health Community Services, Auckland District Health Board, Private Bag
92065, Auckland, New Zealand.

This report describes the epidemiology, investigation and control of a hepatitis 
A (HAV) outbreak in New Zealand. Descriptive and analytical epidemiology,
virology, product traceback and an orchard investigation were carried out. A
case-control study revealed that 56% of 39 cases had consumed raw blueberries,
compared with 14% of 71 controls (odds ratio 7.6; 95% confidence intervals
2.6-22.4). Traceback of product through retailers and wholesalers implicated a
single commercial orchard. Hepatitis A virus was detected by reverse
transcriptase polymerase chain reaction in faecal specimens from cases as well as
a blueberry product from the orchard. Presence of hepatitis A virus was confirmed
by DNA hybridization and sequencing of PCR products. Sanitary audit of the
orchard revealed multiple opportunities for contamination of blueberries by
pickers. This outbreak highlights the need for food safety programmes in the
berry fruit industry.

PMID: 12948375 [PubMed - indexed for MEDLINE]

473: Int Immunopharmacol. 2003 Oct;3(10-11):1549-55.

Analysis of Ig/Ig two-component-determined circulating immune complexes (TCIC)
provide new insights into host immunity.

Wang S, Yang T, Zhang J, Xiao S, Peng X.

The Key Laboratory of Education Ministry for Cell Biology and Tumor Cell
Engineering, Department of Biology, School of Life Sciences, Xiamen University,
Xiamen, Fujian 361005, PR China.

There have been many reports on circulating immune complexes (CIC), but
information regarding Ig/Ig two-component-determined circulating immune complexes
(TCIC) is not available. In the present study, we measured the levels of
heterogeneous Ig/Ig two-component-determined circulating immune complexes
(Ig/Ig-TCIC) in healthy individuals and patients with hepatitis A, Graves'
disease and gastric cancer. The heterogeneous Ig/Ig-TCIC was dissected into
IgM/IgG-TCIC, IgG/IgA-TCIC and IgA/IgM-TCIC by use of coating and detecting
antibodies. The current study has been carried out in 383 cases of healthy
individuals, 97 cases of hepatitis A, 108 cases of Graves' disease and 126 cases 
of gastric cancer. We found that changes on the levels of IgM/IgG-TCIC and
IgG/IgA-TCIC is a common feature in patients studied in this study. A total of
71.4% and 80% of patients with gastric cancer had decreased IgM/IgG-TCIC and
IgG/IgA-TCIC, respectively. In addition, elevated frequencies were found in
patients with hepatitis A and Graves' diseases for IgM/IgG-TCIC (51.5% and 38.0%,
respectively) and IgG/IgA-TCIC (29.9% and 19.4%, respectively). In summary, our
results suggest that Ig/Ig-TCIC may be a hallmark for evaluation of host
immunity. Decreased frequency in gastric cancer and increased frequencies in
hepatitis A and Graves' disease forms a peculiar trait for detection of
IgM/IgG-TCIC and IgG/IgA-TCIC. Our findings have, thus, provided new insights
into circulating immune complexes.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12946452 [PubMed - indexed for MEDLINE]

474: Expert Opin Biol Ther. 2003 Sep;3(6):965-74.

Prevention of hepatitis A by vaccination.

Franco E, Giambi C, Ialacci R, Maurici M.

Department of Public Health, University Tor Vergata, Via Montpellier, 1 - 00133
Rome, Italy. franco@med.uniroma2.it

Inactivated hepatitis A vaccines have been available for more than a decade.
Characteristics of the vaccines, comparative data among different formulations
and the possibility of combination and association with other vaccines are
reviewed in this article. Hepatitis A vaccines show high immunogenicity with
different schedules and associations, induce long-term protection irrespective of
timing of booster dose, and present an excellent safety profile. Pre-exposure
efficacy has been demonstrated in large trials and postexposure protection has
been described in family contacts of acute cases. The recommendations for the use
of hepatitis A vaccines for immunisation campaigns and for targeted groups, such 
as travellers and people at risk for occupational and iatrogenic exposure or
lifestyle behaviours, are discussed. Aspects related to economic analysis of
vaccination strategies are also considered.

Publication Types: 
    Review

PMID: 12943455 [PubMed - indexed for MEDLINE]

475: Hepatology. 2003 Sep;38(3):613-8.

Comment in:
    Hepatology. 2003 Sep;38(3):554-6.

Viral and clinical factors associated with the fulminant course of hepatitis A
infection.

Rezende G, Roque-Afonso AM, Samuel D, Gigou M, Nicand E, Ferre V, Dussaix E,
Bismuth H, Féray C.

Centre Hépato-Biliaire, Equipe Propre de l'Institut National de la Santé, Unité
propre de recherche de l'enseignement supérieur No. 3541, Formation de recherche 
associée à l'Association Claude Bernard, Villejuif, France.

Fulminant hepatitis is a severe complication of hepatitis A virus infection. Its 
mechanism is unknown. Liver transplantation can be necessary, but spontaneous
recovery is frequent. There are no data on the level of viral replication
according to the clinical form of hepatitis A. We reviewed the files of 50
patients with acute hepatitis A. Nineteen patients had fulminant hepatitis
(defined by encephalopathy and factor V <50%), and, from them, 10 patients
underwent transplantation. Hepatitis A virus (HAV) RNA was quantified by
real-time PCR on sera obtained at admission. The genotype was determined by
phylogenetic analysis of HAV RNA. HAV RNA was detected in serum by RT-PCR in 39
out of 50 patients. Encephalopathy and low factor V level were significantly
related to female gender, HAV PCR negativity (9/19 vs. 5/31, respectively; P
=.03), a low serum HAV RNA level (log, 3.6 +/- 0.6 vs. 4.4 +/- 0.9, respectively;
P =.02), genotypes other than IA, and acetaminophen intake. In multivariate
analysis, low or undetectable HAV viral load and a high bilirubin level were
independently associated with both low factor V levels and fulminant hepatitis
and also with death or transplantation. In conclusion, HAV-related liver failure 
is due to an excessive host response associated with a marked reduction in viral 
load. Serum HAV RNA assay could be of help in the management of severe hepatitis 
A.

PMID: 12939587 [PubMed - indexed for MEDLINE]

476: J Infect Dis. 2003 Sep 1;188(5):671-7. Epub 2003 Aug 11.

Efficacy of virosome hepatitis A vaccine in young children in Nicaragua:
randomized placebo-controlled trial.

Mayorga Pérez O, Herzog C, Zellmeyer M, Loáisiga A, Frösner G, Egger M.

Department of Microbiology and Parasitology, Faculty of Medicine, University of
León, Nicaragua.

Immunization of young children could control hepatitis A virus (HAV) infection,
but the efficacy of hepatitis A vaccines in early childhood is unknown. In a
randomized, double-blind trial of a single dose of a virosome-formulated,
aluminum-free inactivated HAV vaccine in Nicaragua, 274 children (age range,
1.5-6 years) received vaccine or placebo injections; 239 children seronegative
for hepatitis A were included in the primary efficacy analysis. HAV infection
documented by immunoglobulin M antibodies was the primary end point. Among
children seronegative for hepatitis A, infection was diagnosed in 4 children in
the vaccine group and 22 children in the placebo group (protective efficacy,
84.6%; 95% confidence interval, 54.7%-96.1%). All infections in children in the
vaccine group occurred within 6 weeks. After 6 weeks, protective efficacy was
100% (79.8%-100%). In children in the placebo group, the incidence of HAV
infection was 17.6 and that of icteric illness was 1.6 cases/100 person-years.
Adverse effects were rare in both children in the vaccine group and children in
the placebo group. A single dose of a hepatitis A virosome vaccine is safe and
protects young children against HAV infection.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 12934183 [PubMed - indexed for MEDLINE]

477: Vaccine. 2003 Sep 8;21(25-26):3556-64.

Cost-effectiveness of hepatitis A vaccine in prevention of secondary hepatitis A 
infection.

Péchevis M, Khoshnood B, Buteau L, Durand I, Piquard Y, Lafuma A.

CEMKA-EVAL, 43 Boulevard Maréchal Joffre, 92340 Bourg-la-Reine, France.
marc.pechevis@cemka.fr

Using a decision-tree based model, we investigated the cost-effectiveness of
several vaccination strategies for household, day care center and nursery/primary
school contacts of primary cases of hepatitis A in France. Depending on the age
groups vaccinated, the cost per symptomatic case avoided varied between 700 and
1,300 Euro (1 Euro = 0.93 US dollars) for household contacts. Vaccination of
contacts in day care centers and schools resulted in cost-savings. However, these
findings are contingent on the limited and controversial data available on
vaccine protective efficacy. In particular, the question of the relative efficacy
of vaccination as compared with the use of immunoglobulins needs further study.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12922083 [PubMed - indexed for MEDLINE]

478: Sex Transm Dis. 2003 May;30(5):411-8.

Factors affecting hepatitis vaccination refusal at a sexually transmitted disease
clinic among men who have sex with men.

Rudy ET, Detels R, Douglas W, Greenland S.

Departments of Health Services and Epidemiology, UCLA, School of Public Health,
650 Charles E. Young Drive South, Box 951772, Los Angeles, CA 90095-1772, USA.
egrudy@earthlink.net

BACKGROUND: Men who have sex with men (MSM) attending sexually transmitted
disease (STD) clinics should be considered candidates for hepatitis A virus (HAV)
and hepatitis B virus (HBV) vaccination. However, vaccination rates in STD
clinics remain less than optimal. GOAL: The goal was to identify factors that
affect HAV and HBV vaccination refusals. STUDY DESIGN: A survey was administered 
to MSM eligible for the vaccinations attending an STD clinic. Vaccines were
offered at the end of the clinic visit. RESULTS: Rates of refusal of HAV
(RefuseA) and HBV (RefuseB) vaccinations were 36% and 38%. Health motivation was 
associated with acceptance, while clinical barriers such as "want to test first
for immunity," and "want to talk to own doctor first" were associated with
refusal. "Not enough time this evening" was most strongly predictive of refusal, 
relative to strongly disagree (risk ratios [RRstrongly agree] and 95% confidence 
limits for RefuseA and RefuseB were 2.69 [1.43, 5.05] and 2.02 [1.05, 3.87],
respectively). CONCLUSIONS: To increase acceptance, patients less
health-motivated should be identified for prevaccination counseling. Some
perceived barriers such as time may be a partial excuse; staff should identify
and address other perceptions that may be influencing patients' decisions.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 12916132 [PubMed - indexed for MEDLINE]

479: Expert Rev Vaccines. 2002 Jun;1(1):9-23.

Inactivated hepatitis A vaccine: immunogenicity, efficacy, safety and review of
official recommendations for use.

André F, Van Damme P, Safary A, Banatvala J.

GlaxoSmithKline Biologicals, Rixensart, Belgium. francis.andre@gskbio.com

There is 10 years of marketing experience with the hepatitis A vaccine Havrix. It
is highly immunogenic, provides lasting protection in healthy individuals and
generates protective levels of antibodies in patients with chronic liver disease 
or impaired immunity. Postmarketing surveillance data have confirmed the
outstanding safety profile of the vaccine. The timing of the booster dose is not 
critical to effectiveness, which has advantages for the protection of travelers
to regions of high endemicity. The vaccine is effective in curbing outbreaks of
hepatitis A and also when administered postexposure, due to rapid seroconversion 
and the long incubation period of the disease. In intermediate endemic regions,
an epidemiological shift in hepatitis A infection has driven the development of
universal preventive strategies to be added to the targeting of at-risk groups.
Existing official recommendations and future directions for vaccine use are
reviewed.

Publication Types: 
    Review

PMID: 12908508 [PubMed - indexed for MEDLINE]

480: Mil Med. 2003 Jul;168(7):565-8.

Pattern of viral hepatitis infection in a selected population from Saudi Arabia.

Memish Z, Qasim L, Abed E, AlBasheer A, Aldraihim A, Knawy B, Hajeer AH.

Department of Pathology and Laboratory Medicine, King Fahad National Guard
Hospital, P.O. 22490, Riyadh 11426, Saudi Arabia.

Viral hepatitis is an important health problem worldwide. Globally, three major
viruses are the leading cause of hepatitis: hepatitis A, B, and C. In this study,
we have investigated the pattern of hepatitis among the National Guard personnel 
and their extended families seen in the central region of Saudi Arabia. The most 
dominant type of hepatitis infection was hepatitis B virus (HBV), followed by
hepatitis C virus (HCV), and to a lesser extent hepatitis A virus (HAV). Our
results showed three different age groups at risk of acquiring the infection:
HAV, which is mainly a disease of the young; HBV, a disease of adolescents and
adults; and HCV, a disease of the elderly. There was no significant difference in
the male:female ratio in HAV and HCV; however, as seen in the developed
countries, more males were affected with HBV than females. These data will pave
the way for further studies by identifying the risk groups for the three major
hepatitis infections and by using the data as a preventive tool to educate those 
risk groups.

PMID: 12901469 [PubMed - indexed for MEDLINE]

481: FEMS Immunol Med Microbiol. 2003 Aug 18;38(1):85-91.

Retrospective detection of a subclinical hepatitis A virus (HAV) epidemic
affecting juvenile cohorts of the Hungarian population.

Pohl O, Brojnás J, Rusvai E, Ordög K, Siska I, Faludi G, Kapusinszky B, Csohán A,
Lendvai K, Lengyel A, Mezey I, Berencsi G.

'B. Johan' National Center for Epidemiology, 1966 Budapest, Hungary.

Sero-epidemiological surveys of serum samples taken in 1982, 1987, 1994 and 1999 
have been performed with hepatitis A virus-specific (HAV-specific) serological
tests. Results obtained during these surveys show that the proportion of
seropositive blood donors decreased from 69% to 18% within 17 years. The authors 
have recognised a (mainly subclinical) epidemic, affecting about 115000 teenagers
in 1992-1994 in Hungary, is a threatening phenomenon. It was calculated that only
about 3600 clinical diseases were associated with the epidemic, recognised
retrospectively from the findings of the four sero-epidemiological surveys.
Epidemiological data indicated that the excess clinical diseases caused by HAV
concentrated in the southern counties of Hungary, which have been affected by the
social and military activities between 1992 and 1994. Due to the decrease of
subjects seropositive for HAV, sera from preselected or actively immunised donors
will be required in the future and vaccination against HAV with killed virus is
likely to be recommended for risk groups. Furthermore, health authorities might
promote active immunisation of young children against HAV infection; for that,
promotion of manufacturing combination vaccines of HAV/HBV/DPT or, for certain
countries, HAV/DPT would be desirable.

PMID: 12900060 [PubMed - indexed for MEDLINE]

482: J Chin Med Assoc. 2003 Jun;66(6):318-22.

Recent advance on viral hepatitis A.

Lee SD.

Department of Medicine, Taipei Veterans General Hospital and National Yang-Ming
University School of Medicine, Taipei, Taiwan, ROC. sdlee@vghtpe.gov.tw

Hepatitis A virus (HAV) infection is an old disease in the world, usually spread 
by the fecal-oral route. The uncomplicated patients usually recovery within 6
months. Its mortality is age-dependent. A high fatality rate with fulminate
course and among chronic hepatitis B or C patients with HAV super-infection was
observed. In recent two to three decades, the improvement of public health and
hygiene has reduced the incidence of hepatitis A in children and adolescents
worldwide; therefore, a massive outbreak of hepatitis A becomes possible among
general population who neither have been infected nor have had any protective
antibodies. Currently, the commercially available inactivated hepatitis A vaccine
is proved to be safe and immunogenic in different risk groups, including children
and adults, in several large clinical trials. Considering the potential for
epidemic outbreak and the severity of the disease, immunization against the
infection among risk population turns important for the prevention and control of
HAV infection.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 12889499 [PubMed - indexed for MEDLINE]

483: Commun Dis Public Health. 2003 Jun;6(2):101-5.

Comment on:
    Commun Dis Public Health. 2003 Jun;6(2):82-4.

Outbreak of hepatitis A infection among intravenous drug users in Suffolk and
suspected risk factors.

Sundkvist T, Smith A, Mahgoub H, Kirkby A, Kent R, Wreghitt T, Davidkin I.

Communicable Disease Control Team, Suffolk Public Health Network, St Clements
Hospital, PO Box 170, Foxhall Road, Ipswich, Suffolk IP3 8LS.
torbjorn.sundkvist@lhp.nhs.uk

A prolonged outbreak of hepatitis A infection amongst drug users in Suffolk
prompted a study of the natural immunity against hepatitis A in this population, 
and a retrospective analysis of the relationship between specific drug-taking
behaviours and the risk of hepatitis A infection. Prior to the outbreak,
age-specific seroprevalence of hepatitis A IgG in drug users was similar to that 
amongst blood donors in the region. Of those without effective immunity,
intravenous drug users, multiple drug users and those injecting frequently were
more likely to have developed hepatitis. The reported frequency of equipment
sharing and the number of injecting partners were not related to the risk of
infection. The potential for blood-to-blood, and a suggested faecal-blood
transmission were considered to be important in propagating the outbreak in this 
population. We suggest that a single dose of hepatitis A vaccine administered
opportunistically should be used in outbreaks involving drug users.

Publication Types: 
    Comment

PMID: 12889287 [PubMed - indexed for MEDLINE]

484: Commun Dis Public Health. 2003 Jun;6(2):97-100.

Changing epidemiology of hepatitis A: should we be doing more to vaccinate
injecting drug users?

Perrett K, Granerød J, Crowcroft N, Carlisle R.

South Yorkshire Health Protection Service, Department of Public Health, Rotherham
Primary Care Trust, Bevan House, Oakwood Hall Drive, Rotherham, South Yorkshire
S60 3AQ. kevin.perrett@rotherhampct.nhs.uk

Since 2001 there have been significant outbreaks of hepatitis A virus (HAV)
across South Yorkshire, largely in intravenous drug users, and HAV infection has 
been reported to be an increasing problem in England and Scotland during this
time. This paper reports a brief investigation to clarify current HAV
epidemiology in England and Wales. The epidemiology of HAV in England, but not
yet Wales, has recently changed. Laboratory reports now show that most cases are 
occurring in young adults, mainly young men, and that the commonest reported risk
group is injecting drug users. That cases may now be concentrated in injecting
drug users is supported by reports from consultants in communicable disease
control (CsCDC). These detail fourteen outbreaks in England in 2002 alone, all
involving injecting drug users. Links to prisons and to the homeless, usually
those in hostels, were also common. A combined Hepatitis A/B vaccine is readily
available and we recommend that this now be used to extend the national
immunisation programme against Hepatitis B in injecting drug users to include
HAV.

PMID: 12889286 [PubMed - indexed for MEDLINE]

485: Med Sci Monit. 2003 Jul;9(7):PH11-4.

Occupational risk of hepatitis A infection among health care providers in
northeastern Poland.

Grzeszczuk A, Sokolewicz-Bobrowska E, Chlabicz S.

Department of Infectious Diseases, Medical University of Białystok, Białystok,
Poland. oliwa@amb.ac.bialystok.pl

BACKGROUND: Vaccinating health care workers against hepatitis A has been
suggested, but it has not been clearly shown that this group is at increased risk
for HAV infection. The objective of our study was to evaluate the prevalence of
anti-HAV antibodies among health care workers, and to assess the risk factors
associated with anti-HAV seropositivity. MATERIAL/METHODS: Total anti-HAV
antibodies in serum were determined among 252 health care workers from three
hospital departments (internal medicine, infectious diseases and surgery) in
Białystok, in northeastern Poland. The control group consisted of 250 age and
sex-matched healthy individuals who are not health-care professionals. RESULTS:
Anti-HAV antibodies were found in 180 of the 252 health care workers (71.4%) and 
in 153 of the 250 healthy controls (61.2%, p<0. 05)). The difference in anti-HAV 
prevalence between health care workers and the control group occurred only in
individuals up to 40 years of age (59.2% and 43.4% respectively, p<0. 05) while
no difference could be seen in those older than 40 years (88.6% and 88.8%
respectively). Among health care workers there was no association between
anti-HAV seropositivity and sex, employment as a physician, nurse or ward
attendant, or ward of employment. Health care workers older than 40 years were
anti-HAV positive more frequently than younger (88.6 and 59.2% respectively,
p<0.05). CONCLUSIONS: In northeastern Poland. younger health care workers ((40
years) may be particularly prone to occupationally acquired hepatitis A
infections.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12883461 [PubMed - indexed for MEDLINE]

486: Eur J Gastroenterol Hepatol. 2003 Aug;15(8):901-6.

Outbreak of hepatitis A in the injecting drug user and homeless populations in
Bristol: control by a targeted vaccination programme and possible parenteral
transmission.

Syed NA, Hearing SD, Shaw IS, Probert CS, Brooklyn TN, Caul EO, Barry RE, Sarangi
J.

Department of Public Health, Avon Health Authority, Bristol, UK.
naveedsyed@yahoo.com

OBJECTIVE: To study the use of hepatitis A virus (HAV) vaccination in controlling
an outbreak of HAV in inner-city Bristol among injecting drug users (IDUs). To
study whether hepatitis C virus (HCV) and hepatitis B virus (HBV) co-infection
increases morbidity. DESIGN: Community-based cohort study. SETTING: Avon Health
Authority area, UK. PARTICIPANTS: All laboratory-confirmed cases of HAV infection
notified in 2000. INTERVENTION: Administration of a targeted vaccination,
education and liaison programme. MAIN OUTCOME MEASURES: Number of cases of HAV
before and after introduction of HAV vaccination programme. Mortality and number 
of patients requiring hospital admission. Association of HCV and HBV co-infection
with hospital admission. RESULTS: Ninety cases of HAV were reported in the first 
6 months of 2000, of whom a substantial number were IDUs and/or inner-city hostel
residents. In the second 6 months of 2000, following the introduction of a
vaccination programme among homeless people, hostel residents, and IDUs, the
number of HAV cases fell to 33. Sixteen patients had evidence of HCV
co-infection. No patient had chronic HBV infection. Two patients died as a result
of HAV, and two subsequently died from drug misuse. Fifty-six per cent of
HCV-co-infected patients required admission to hospital compared with 28%
non-HCV-co-infected patients. CONCLUSIONS: This is the first reported successful 
use of vaccination to control an outbreak of HAV in a population of IDUs and to
prevent transmission to the wider population. HCV co-infection appears to
increase the severity of HAV illness, as demonstrated by increased incidence of
hospital admission.

PMID: 12867801 [PubMed - indexed for MEDLINE]

487: J Infect. 2003 Aug;47(2):125-8.

Hepatitis A virus infection in hepatitis C Brazilian patients.

Devalle S, de Paula VS, de Oliveira JM, Niel C, Gaspar AM.

Department of Virology, Oswaldo Cruz Institute, Avenida Brasil 4365, Rio de
Janeiro, RJ 21045-900, Brazil.

OBJECTIVE: HAV infection in patients with pre-existing chronic liver disease has 
been associated with increased rate of fulminant hepatitis and mortality. The aim
of this study was to investigate the presence of serological and molecular HAV
markers in a population of HCV infected patients. PATIENTS AND METHODS: The
presence of total and IgM anti-HAV antibodies was investigated in 197 patients
(mean age 44.8+/-12.5 years) referred to the Brazilian Reference Center for Viral
Hepatitis and who tested positive for anti-HCV antibodies and HCV RNA. HAV RNA
was investigated by reverse transcription-nested PCR in these patients.Results.
One hundred seventy patients (86%) had total, but not IgM anti-HAV antibodies,
being therefore, immune to hepatitis A, while 27 (14%) were not. A high
proportion (6/27, 22%) of the susceptible patients presented markers of recent
HAV infection: One patient was IgM anti-HAV positive, three were HAV RNA
positive, and two presented both markers. By nucleotide sequencing, it was
demonstrated that the HAV isolates infecting these patients belonged to
subgenotypes 1A and 1B. CONCLUSIONS: Superinfection with HAV was a common event
in the group of HCV infected patients under study. Implementation of hepatitis A 
vaccination should be considered for this population.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12860145 [PubMed - indexed for MEDLINE]

488: J Med Virol. 2003 Sep;71(1):1-6.

HAV replication in acute hepatitis with typical and atypical clinical course.

Sagnelli E, Coppola N, Marrocco C, Onofrio M, Scarano F, Marotta A, Scolastico C,
Catuogno A, Salzillo A, Sagnelli C, Piccinino F, Filippini P.

Division of Infectious Diseases, Azienda Ospedaliera San Sebastiano, Caserta,
Italy. evangelista.sagnelli@unina2.it

The correlation between the length of viremia as detected by reverse
transcriptase-polymerase chain reaction (RT-PCR) and the clinical course of
hepatitis A virus (HAV) infection was studied. Sixty-six consecutive patients
with acute hepatitis A who were admitted to hospital in two infectious disease
units in southern Italy were enrolled: 57 had a self-limited course of the
disease (typical course), 4 a prolonged course, and 5 relapsing hepatitis. Plasma
HAV RNA was sought by RT-PCR, using primers made at 5'-NTR of HAV, designed to
amplify a 273-bp fragment and detected by 2% agarose gel and by hybridization
with a specific biotinylated probe. In four patients with prolonged acute
hepatitis A, the plasma HAV RNA, which was positive on the day of admission to
hospital, was found to be negative from day 62, 46, 84, and 105, respectively,
after the onset of the symptoms. In patients with relapsing hepatitis, HAV
viremia paralleled the clinical and biochemical course of disease. In all
patients with a typical self-limiting course, clearance of plasma HAV RNA was
observed within 20 days of the onset of symptoms. In most patients, plasma HAV
viremia became undetectable before the normalization of serum aminotransferases, 
underlining the importance of the immune reaction in the pathogenesis of acute
hepatitis A. The data also suggest that the detection of plasma HAV RNA after 20 
days of illness may predict a prolonged course of the disease, but relapsing
hepatitis remains unpredictable on the basis of plasma HAV determination.
Copyright 2003 Wiley-Liss, Inc.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12858402 [PubMed - indexed for MEDLINE]

489: J Community Health. 2003 Aug;28(4):233-46.

Economic impact of a hepatitis A epidemic in a mid-sized urban community: the
case of Spokane, Washington.

Bownds L, Lindekugel R, Stepak P.

Department of Economics, Eastern Washington University, Cheney, WA 99004-2429,
USA. lbownds@ewu.edu

Data reported here represent an effort to build on previous work regarding the
costs of hepatitis A. We expand this work to include an estimation of the costs
of hepatitis A on a community wide basis. In addition to calculating the costs of
disease management and health care delivery, we include an analysis of additional
child care costs, lost productivity, costs associated with outbreak management,
and the impact on affected restaurants that required public notification and the 
administration of Immune Globulin to patrons. The work reported here is specific 
to Spokane county, Washington. The objective is to enable the Spokane Regional
Health District to communicate to the community costs of managing an outbreak of 
hepatitis A and to inform implementation of a hepatitis A vaccination program on 
a community wide basis. The average cost (direct and indirect) per case for the
entire sample is 2,683 dollars. The estimated total cost for the sample (145
cases) is approximately 370,193 dollars. Inpatient hospital care is the largest
direct medical expense and lost productivity is a major indirect cost to the
community. Lessons learned from undertaking this task include: (1) costs incurred
are not immediately obvious, (2) without infrastructure in place, tracking costs 
is difficult, if not impossible, (3) potential for large expenditures is
apparent, (4) estimates are consistent with those generated in previous studies, 
and (5) previous findings of vaccination of certain high-risk populations as a
cost-efficient approach is corroborated.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12856793 [PubMed - indexed for MEDLINE]

490: World J Gastroenterol. 2003 Jul;9(7):1508-11.

Detection of anti-HAV antibody with dot immunogold filtration assay.

Shao ZJ, Xu DZ, Yan YP, Li JH, Zhang JX, Zhang ZY, Pan BR.

Department of Epidemiology, Fourth Military Medical University, Xi'an 710032,
Shaanxi Province, China.

AIM: To establish a rapid, sensitive and specific immunogold assay for detection 
of hepatitis A virus infection. METHODS: Rabbit monoclonal antibodies to
anti-human IgM and IgG (Dako) were dotted on a nitrocellulose membrane (NCM)
respectively to capture the human sera IgM and IgG. Then the captured antibodies 
would conjugate to HAV antigen, which was revealed by mouse anti-HAV IgG
conjugated to gold particles. Final results were assessed by blind method.
RESULTS: Sera from 96 patients with acute hepatitis were used for our study.
Compared with well-recognized standard (Abbott Laboratory, USA), the sensitivity 
and specificity of IgM-DIGFA (self-made) were 91.3 % (42/46) and 96.0 % (48/50), 
and those of IgM-ELISA (Kehua, Shanghai) were 97.8 % (45/46) and 100.0 % (50/50).
The identical results were produced from the study with reagents at different
conditions, and the study was repeated in 15 negative sera and 10 positive sera. 
The serum anti-HAV IgG was tested with DIGFA at the same time. In comparison with
ELISA, the sensitivity and specificity of DIGFA for IgG anti-HAV were 87.2 %
(41/47) and 91.8 % (45/49), respectively. CONCLUSION: This assay can detect
anti-HAV IgM and IgG simultaneously, and be done within 3 minutes. The
simplicity, rapidity and specificity of the assay were useful for screening and
epidemiological study.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 12854152 [PubMed - indexed for MEDLINE]

491: Hepatogastroenterology. 2003 Jul-Aug;50(52):1066-8.

Does previous hepatitis A infection affect the clinicopathological status of
chronic hepatitis C?

Chlabicz S, Grzeszczuk A, Panasiuk A, Prokopowicz D.

Department of Family Medicine and Community Nursing, Medical Academy of
Bialystok, Mieszka I 4B 15-054 Bialystok, Poland. schlabicz@poczta.onet.pl

BACKGROUND/AIMS: The aim of the study was to evaluate the effect of previous
infection with hepatitis A virus on histopathological and biochemical changes in 
chronic hepatitis C. METHODOLOGY: Anti-hepatitis A virus antibodies, liver
histopathology and alanine aminotransferase activity were determined in 82
patients with chronic hepatitis C. The liver biopsy specimen of each patient was 
examined according to Scheuer's classification to indicate the severity of the
inflammatory cell infiltration in the portal/periportal and parenchymal area
(grading) in a 0-4 scale and fibrous stage (staging) in a 0-4 scale. RESULTS: The
overall prevalence of anti-hepatitis A virus antibodies was 63.1%.
Anti-HAV-positive patients were significantly older than anti-HAV-negative ones
(mean age 42.5 and 33.1 years respectively, p < 0.05). After stratifying the
study sample into two age groups (< 40 years and > or = 40 years) the percentage 
of anti-HAV-positive individuals was similar irrespective of grading, staging
score or presence of steatosis. No remarkable differences were observed between
the anti-HAV-positive and -negative group in the mean ALT activity. CONCLUSIONS: 
The results of our study indicate that previous hepatitis A is not associated
with progressive course of chronic hepatitis C.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12845983 [PubMed - indexed for MEDLINE]

492: Trop Gastroenterol. 2002 Oct-Dec;23(4):170-1.

Seroprevalence of hepatitis A virus antibody in patients with chronic liver
disease--experience from a tertiary care hospital in north India.

Dhotial A, Kapoor D, Kumar N.

Department of Gastroenterology, GB Pant Hospital, New Delhi-110 002.

Patients with chronic liver disease of any etiology are at a high risk for a more
severe outcome when superinfected with hepatitis A virus (HAV). Prevention of
hepatitis A, by inactivated vaccine has been shown to be safe and effective in
this subgroup of patients. Most countries in the West recommend prophylaxis
against hepatitis A virus for patients with chronic liver disease. However,
hepatitis A virus is endemic in India. Before advocating a uniform prophylaxis
against hepatitis A for chronic liver disease patients in India, we prospectively
evaluated the seroprevalence of hepatitis A virus antibody (Anti HAV) among the
patients with cirrhosis of liver registered at our hospital, using a commercial
enzyme-immunoassay (ELISA). Prevalence of protective antibody against HAV among
the 42 Cirrhotic patients included in the study was documented to be 97.6%
(41/42). Therefore, vaccination against hepatitis A virus infection may not be
needed among patients with chronic liver disease in our population. However,
further studies including adequate sample size is needed to confirm the
observation encountered in the present study.

Publication Types: 
    Evaluation Studies

PMID: 12833702 [PubMed - indexed for MEDLINE]

493: J Hosp Infect. 2003 Jun;54(2):135-40.

Hepatitis A virus seropositivity among hospital and community healthcare workers 
in Israel-the role of occupation, demography and socioeconomic background.

Chodick G, Ashkenazi S, Aloni H, Peled T, Lerman Y.

Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv, Israel.
chodick@post.tau.ac.il

Hospital and community-clinic workers were tested for hepatitis A virus
antibodies (HAV)-IgG to identify variables associated with presence of (HAV-IgG) 
and to determine whether sociodemographic background may explain all differences 
in HAV seropositivty among healthcare workers. Logistic regression analysis was
used to identify variable associated with HAV-immunity. Multivariate logistic
regression analysis revealed that HAV-seroprevalence correlated significantly
(P<0.01) with age, siblings, residence in rural areas and origin. Nurse aides had
an increased risk for HAV seropositivity (OR=5.04; 95% CI: 1.49-17.08) whereas
physicians had a lower risk (OR=0.54: 95% CI: 0.30-0.98). Age and socioeconomic
background were independently correlated with HAV immunity but did not explain
all difference in HAV-seroprevalence. The higher susceptibility and elevated
incidence of hepatitis A amongst physicians, prioritize primary prevention in
this group.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12818588 [PubMed - indexed for MEDLINE]

494: MMWR Morb Mortal Wkly Rep. 2003 Jun 20;52(24):565-7.

Foodborne transmission of hepatitis A--Massachusetts, 2001.

Centers for Disease Control and Prevention (CDC).

Hepatitis A virus (HAV) is transmitted typically from person to person by the
fecal-oral route. Foodborne transmission occurs when an HAV-infected food handler
contaminates food during preparation or when food is contaminated during
harvesting or processing before reaching the food service establishment or home. 
Postexposure prophylaxis (PEP) with immune globulin (IG) can prevent hepatitis A 
among exposed persons if administered within 14 days of exposure. However, the
decision about whether to implement PEP for persons who eat food prepared by an
infected food handler depends on an assessment of the duties performed by the
food handler and personal hygiene while potentially infectious, which are often
difficult to determine. This report summarizes the investigation of an outbreak
of foodborne hepatitis A in Massachusetts in which a food handler with hepatitis 
A, who was considered unlikely to transmit HAV, was implicated as the source. The
findings underscore challenges faced by local and state health departments when
determining whether PEP is appropriate.

PMID: 12816107 [PubMed - indexed for MEDLINE]

495: J Clin Gastroenterol. 2003 Jul;37(1):79-81.

Acute viral cholecystitis due to hepatitis A virus infection.

Ozaras R, Mert A, Yilmaz MH, Celik AD, Tabak F, Bilir M, Ozturk R.

Department of Infectious Diseases and Clinical Microbiology, Cerrahpasa Medical
Faculty, 34303 Cerrahpasa, Istanbul, Turkey. rozaras@yahoo.com

Acute hepatitis A virus (HAV) infection is frequent in developing countries.
Although some gallbladder abnormalities are defined during the course, an acute
cholecystitis is extremely rare. We here report 2 additional cases of
cholecystitis due to acute HAV infection and review the previously reported 2
cases. One of our patients was admitted with jaundice and a suspicious portal
mass with a presumed diagnosis of cholagiocarcinoma. The other presented with
jaundice, abdominal pain, and constitutional symptoms. Both patients were planned
to be operated on. During the follow-up, absence of fever, leukocytosis,
acute-phase protein response, and calculus in biliary system were against the
diagnosis of a bacterial cholecystitis. Moreover the course of cholecystitis was 
closely parallel to that of the HAV infection. Both patients were managed
conservatively. It was concluded that rare, acute viral cholecystitis can develop
during the course of acute HAV infection.

Publication Types: 
    Case Reports

PMID: 12811216 [PubMed - indexed for MEDLINE]

496: J Gastroenterol Hepatol. 2003 Jul;18(7):822-7.

Seroepidemiology of hepatitis A virus infection among school children in Delhi
and north Indian patients with chronic liver disease: implications for HAV
vaccination.

Acharya SK, Batra Y, Bhatkal B, Ojha B, Kaur K, Hazari S, Saraya A, Panda SK.

Departments of Gastroenterology and Pathology, All India Institute of Medical
Sciences New Delhi, India.

BACKGROUND: Universal vaccination against hepatitis A virus (HAV) has been
recommended for children because of the changing epidemiological pattern of HAV. 
Vaccination has also been advised for patients with chronic liver disease as HAV 
superinfection in these patients can result in severe or even fatal disease. In
India, the indications for HAV vaccination are not clear due to contradictory
seroepidemiological data in children and lack of data on HAV seroprevalence in
patients with chronic liver disease. METHODS: Sera were collected from children
studying in two government-run schools and from patients with chronic liver
disease attending the Liver Clinic at the All India Institute of Medical Sciences
(AIIMS). The sera were tested for anti-HAV antibodies. The incidence of
HAV-induced acute hepatitis and acute liver failure at AIIMS over the last 10
years was also assessed. RESULTS: A total of 93.2% (1328/1424) of the school
children between 4-18 years of age who were included in the study had anti-HAV
antibody in their sera. Eighty percent of the children had antibodies against HAV
in their sera by the age of 5 years, whereas all the children above 16 years were
positive for anti-HAV antibody. A total of 256 patients with chronic liver
disease (94 with cirrhosis of the liver, 160 with chronic hepatitis) were tested 
for the presence of anti-HAV antibody. Of them, 97.6% (248/254) had anti-HAV
antibody in their sera. The annual frequency of HAV-induced acute viral hepatitis
and acute liver failure at AIIMS during the last 10 years did not show any
change. CONCLUSION: Mass vaccination against HAV is not required in north India
because of the presence of protective antibodies against HAV in the majority of
the population. Copyright 2003 Blackwell Publishing Asia Pty Ltd

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12795755 [PubMed - indexed for MEDLINE]

497: Can J Public Health. 2003 May-Jun;94(3):176-9.

Hepatitis A among residents of First Nations Reserves in British Columbia,
1991-1996.

Jin A, Martin JD.

First Nations and Inuit Health Branch, Health Canada. ajin@unixg.ubc.ca

BACKGROUND: Hepatitis A spreads by the fecal-oral route. We hypothesize that it
is more common in Aboriginal communities because of poverty, crowded housing and 
inadequate or substandard water and sewage systems. METHODS: We tabulated
on-reserve cases reported to First Nations and Inuit Health Branch, Health
Canada. We obtained information on community water supply, sewage disposal and
mean population per housing unit, from site inspections in a 1994 survey.
RESULTS: Crude incidence on-reserve was 31 per 100,000 persons per year (95% CI: 
25 to 37), twice as high as in the general population of BC (15.1 per 100,000).
Higher incidence of hepatitis A was associated with more persons per housing unit
and with presence of community water supply problems. CONCLUSIONS: An ecologic,
multi-factorial approach to disease prevention is needed, including upgrading
housing and sanitary infrastructure, specific measures (i.e., hepatitis A
vaccination) and general measures (e.g., education, poverty reduction, population
planning).

PMID: 12790489 [PubMed - indexed for MEDLINE]

498: J Med Virol. 2003 Jul;70(3):343-9.

Genetic analysis of HAV strains recovered from patients with acute hepatitis from
Southern Italy.

Chironna M, Grottola A, Lanave C, Villa E, Barbuti S, Quarto M.

Department of Internal Medicine and Public Health, Hygiene Section, University of
Bari, Italy. m.chironna@igiene.uniba.it

Southern Italy is an endemic area for HAV infection contributing to the majority 
of Italian hepatitis A cases. Using molecular analysis, HAV strains have been
classified in distinct genotypes and subgenotypes. To characterize HAV wild-type 
strains circulating in Southern Italy, sequence analysis of VP3-VP1 and VP1/2A
junction regions of HAV isolates recovered from 25 patients with acute hepatitis 
during 2000 and 2001 was carried out. HAV isolates showed a degree of identity,
after pairwise comparison with one another, ranging from 91.9-100% in the VP3-VP1
junction region and 89.9-100% in the VP1/2A junction region. All strains belonged
to genotype I, with 84% (21/25) of samples clustering in subgenotype IA and 16%
(4/25) in subgenotype IB. Cocirculation of subgenotypes IA and IB was observed
among isolates from 2000, whereas all strains from 2001 were subgenotype IA. In
addition, the subgenotype IA strains formed different clusters, one of which was 
related closely to some Cuban strains, showing a percent similarity of 98.8% in
the 168-base pair segment encompassing the VP1/2A junction and the same amino
acid substitution. The latter finding suggests that this subgenotype variant
circulates also in the Mediterranean area. The results of the phylogenetic
analysis confirm the genetic heterogeneity among HAV strains in Western Europe.
Copyright 2003 Wiley-Liss, Inc.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 12766995 [PubMed - indexed for MEDLINE]

499: Clin Lab Sci. 2003 Spring;16(2):99-106.

Validity of injecting drug users' self report of hepatitis A, B, and C.

Schlicting EG, Johnson ME, Brems C, Wells RS, Fisher DG, Reynolds G.

University of Rhode Island, Kingston, RI, USA.

OBJECTIVE: To test the validity of drug users self-reports of diseases associated
with drug use, in this case hepatitis A, B, and C. DESIGN: Injecting drug users
(n = 653) were recruited and asked whether they had been diagnosed previously
with hepatitis A, B, and/or C. These self-report data were compared to total
hepatitis A antibody, hepatitis B core antibody, and hepatitis C antibody
seromarkers as a means of determining the validity of the self-reported
information. SETTING: Anchorage, Alaska. PARTICIPANTS: Criteria for inclusion
included being at least 18-years old; testing positive on urinalysis for cocaine 
metabolites, amphetamine, or morphine; having visible signs of injection (track
marks). INTERVENTION: Serological testing for hepatitis A, B, and C. MAIN
OUTCOME: Findings indicate high specificity, low sensitivity, and low kappa
coefficients for all three self-report measures. RESULTS: Subgroup analyses
revealed significant differences in sensitivity associated with previous
substance abuse treatment experience for hepatitis B self-report and with gender 
for hepatitis C self-report. CONCLUSION: Given the low sensitivity, the validity 
of drug users, self-reported information on hepatitis should be considered with
caution.

Publication Types: 
    Evaluation Studies
    Research Support, U.S. Gov't, P.H.S.

PMID: 12757189 [PubMed - indexed for MEDLINE]

500: J Clin Psychiatry. 2003 May;64(5):540-5.

Prevalence of hepatitis A, hepatitis B, and HIV among hepatitis C-seropositive
state hospital patients: results from Oregon State Hospital.

Meyer JM.

University of California, San Diego, USA. jmmeyer@ucsd.edu

BACKGROUND: Multiple studies have shown that individuals with severe mental
illness are at increased risk for acquiring infection from human immunodeficiency
virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV). Moreover,
patients with chronic HCV infection are at risk for fulminant hepatitis from
acquired infection with hepatitis A virus (HAV) or HBV, but there are limited
data on the prevalence of HIV, HAV, and HBV in chronically hospitalized U.S.
psychiatric patients without mental retardation who are HCV-seropositive. To
address this issue, a comprehensive screening program was commenced at Oregon
State Hospital (Salem, Ore.) beginning in 1999. METHOD: The computerized records 
of all non-geriatric adult inpatients at Oregon State Hospital on April 23, 2001,
were reviewed to assess physician compliance with screening and the prevalence of
infection with HIV, HAV, HBV, and HCV. RESULTS: Among the 535 patient records
reviewed, 94.8% of patients were screened for HCV, of whom 20.3% were
seropositive. Among HCV-seropositive patients, only 1.9% were not screened for
HAV and HBV, but 23.3% were not tested for HIV. In the HCV-seropositive group,
35.9% were HAV-positive, 49.5% HBV-positive, and 2.6% HIV-positive. CONCLUSION:
Chronic psychiatric inpatients have high HCV prevalence rates. Hepatitis
C-seropositive individuals may be at risk for complications unless vaccinated for
HAV and HBV.

Publication Types: 
    Comparative Study

PMID: 12755656 [PubMed - indexed for MEDLINE]

501: J Viral Hepat. 2003 May;10(3):157-8.

Who should receive hepatitis A vaccine?

Arankalle VA, Chadha MS.

Hepatitis Division, National Institute of Virology, 20-A Dr Ambedkar Road, Pune, 
India-411001. aarankalle@hotmail.com

Though a potent vaccine represents a powerful preventive tool, the policy of its 
use is governed by epidemiological and economical factors. Hepatitis A, an
enterically transmitted disease shows distinct association with socio-economic
status, populations with improvement experiencing lower exposure to the virus.
With the availability of vaccine, it is pertinent to consider its use in the
effective control of the disease. However, with the varied epidemiological
patterns and economical constraints in different countries it does not seem to be
possible to evolve universal policy for immunization. Though, universal
immunization may be the most effective way of control, the same is not practical 
for many countries. It is proposed that irrespective of endemicity of hepatitis
A, high-risk groups such as travelers to endemic areas, patients suffering from
chronic liver diseases, HBV and HCV carriers, tribal communities with high HBV
carrier rates, food handlers, sewage workers, recipients of blood products,
troops, and children from day-care centers should be immunized with hepatitis A
vaccine. In addition, for populations with intermediate prevalence, infants,
children from affordable families may be immunized. As coupling the vaccine with 
EPI schedule would be beneficial, use of combined A & B or A, B & E vaccine may
be an attractive alternative.

Publication Types: 
    Review

PMID: 12753332 [PubMed - indexed for MEDLINE]

502: Helicobacter. 2003 Jun;8(3):168-72.

Helicobacter pylori and hepatitis A virus infection in school-aged children on
two isolated neighborhood islands in Taiwan.

Chen LK, Hwang SJ, Wu TC, Chu CH, Shaw CK.

Department of Family Medicine, Children's Medical Center, Taipei Veterans General
Hospital, Taiwan, ROC.

BACKGROUND: The transmission routes of Helicobacter pylori and hepatitis A virus 
(HAV) infections have been extensively discussed in previous literature. However,
whether H. pylori and HAV shared the same transmission pattern or not remains
unclear. Lower socioeconomic status was recognized as a consistent risk factor to
both infections. However, whether fecal-oral transmission was a risk factor to
both infections is still under debate. MATERIALS AND METHODS: In 1996, we
conducted a cross-sectional study to evaluate the seroprevalence of antibody to
H. pylori and HAV among the randomly selected school-aged children (age between
13 and 15) on Green Island (n = 91) and Lanyu Island (n = 138) (two isolated
neighborhood islands near Taiwan Main Island). RESULTS: The seroprevalence of H. 
pylori and HAV on the Green Island were 82.4% and 5.5%, respectively. The
seroprevalence of H. pylori and HAV on Lanyu Island were 71.0% and 90.6%,
respectively. H. pylori seroprevalence of all children and the subgroup of
13-year-olds was significantly lower on Lanyu Island than Green Island. However, 
it was not significantly different in subgroups of 14- and 15-year-olds. HAV
seroprevalence was significantly higher on Lanyu Island than Green Island among
all children and in each age subgroup. The correlation of H. pylori infection and
HAV infection did not demonstrate significant linear correlation on both islands.
CONCLUSIONS: In conclusion, H. pylori and HAV infections in school-aged children 
of 13-15 years of age on Green Island and Lanyu Island did not demonstrate
significant correlation. The results of this study imply that H. pylori and HAV
may share different transmission routes of infection.

PMID: 12752727 [PubMed - indexed for MEDLINE]

503: J Natl Med Assoc. 2003 Apr;95(4 Suppl):31S-36S.

Hepatitis A vaccination among young African American men who have sex with men in
the deep south: psychosocial predictors.

Rhodes SD, Yee LJ, Hergenrather KC.

Department of Health Behavior and Health Education, University of North Carolina 
School of Public Health, Campus Box 7440, Chapel Hill, North Carolina 27599-7440,
USA. Scott_Rhodes@unc.edu

Despite recommendations for vaccination against hepatitis A (HAV) of men who have
sex with men (MSM), most remain unvaccinated. This study was designed to identify
attitudes and beliefs associated with vaccination against HAV using a
conventional outreach sample of African American MSM in Birmingham, Alabama. Of
107 participants, nearly 34% reported being vaccinated against HAV. Over half of 
the participants reported 10 or more different lifetime male sexual partners, and
a third reported having had intercourse with females, as well as, males within
the past 5 years. About 10% of the participants reported condom use over half of 
the time during oral intercourse, and 50% of the participants reported using a
condom over half the time during anal intercourse. In multivariable analysis,
predictors of HAV vaccination were a decreased perception of the practical
barriers to HAV vaccination (odds ratio [OR], 0.05; 95% confidence interval [CI]:
0.01-0.18, P = 0.002); increased health provider communication (OR, 9.89; 95% CI:
2.74-35.65, P = 0.02); and increased perceived personal self-efficacy to complete
the two-dose series (OR, 7.31; 95% CI: 2.38-22.45, P = 0.02). Our findings
underscore the need to increase vaccination through innovative approaches to
reduce perceived barriers to vaccination while increasing provider-patient
communication and self-efficacy to complete the vaccine series.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12749607 [PubMed - indexed for MEDLINE]

504: Vaccine. 2003 Jun 2;21(19-20):2250-7.

The use of hepatitis a vaccination in Italy: an economic evaluation.

Demicheli V, Carniglia E, Fucci S.

Servizio Epidemiologico, ASL 20 Alessandria and Cochrane Vaccines Field, Via
Venezia 6, 15100 Alessandria, Italy. demichelivittorio@asl20.piemonte.it

We report on the conduct and results of an economic model of two different
strategies of vaccination against hepatitis A in Italy. In strategy 1 (universal 
vaccination), all newborns are vaccinated simultaneously with MMR at 15 months
and all 12 year olds are vaccinated with combined hepatitis A and B vaccine. In
strategy 2 (contacts' vaccination) only subjects with a close social and spatial 
relationship with the sick are vaccinated.In strategy 1 costs per avoided case
and net costs per avoided case values are always very high. Net costs become very
low when newborns and 12 year olds are vaccinated, and become negative
(indicating a potential gain) when 12 year olds are vaccinated. From an economic 
viewpoint, universal vaccination appears recommendable only in epidemic
conditions. For strategy 2 our model shows that cost for avoidable case are very 
low and net costs for avoided case are always negative, showing the potential
presence of an absolute benefit. We conclude that in Italy mass vaccination
appears economically worthwhile only during epidemics but vaccination of contacts
is an economically worthwhile routine measure.

PMID: 12744852 [PubMed - indexed for MEDLINE]

505: Vaccine. 2003 Jun 2;21(19-20):2246-9.

The role of vaccine in controlling hepatitis A epidemics.

D'Argenio P, Adamo B, Cirrincione R, Gallo G.

Istituto Superiore di Sanità, Laboratorio di Epidemiologia e Biostatistica, Viale
Regina Elena 299, 00161 Rome, Italy. dargenio@iss.it

We report the conduct and results of a review of recent literature to describe
various types of epidemics and outbreaks in Italy or countries with similar
epidemiological profiles and to assess vaccine use in outbreak situations.We
identified three scenarios most likely to occur in Italy: outbreaks occurring in 
small closed communities (nursery or a primary school), outbreaks in communities 
of limited dimensions (small towns or villages) and open community settings in
which epidemics occur at regular intervals (person-to-person transmission).In
closed communities we recommend vaccination of family members and school
personnel living or working in close proximity to the index case as well as
classmates. We also recommend vaccination when there is a proof of secondary
transmission within the community.In small open communities we recommend
vaccination of more susceptible age groups such as children and adolescents. For 
large open communities the only practicable alternative strategy is vaccination
of close family contacts of acute cases couple with non-immunity boosting control
measures.

PMID: 12744851 [PubMed - indexed for MEDLINE]

506: Vaccine. 2003 Jun 2;21(19-20):2238-41.

HAV infection in chronic liver disease: a rationale for vaccination.

Almasio PL, Amoroso P.

Cattedra di Gastroenterologia, University of Palermo, Clinica Medica I, Piazza
delle Cliniche 2, 90127 Palermo, Italy. palmasio@unipa.it

We report the conduct and results of a systematic search of the literature to
assess whether exposure to HAV could induce a fatal deterioration of liver
diseases. We assessed 30 studies and found evidence of progressive decrease of
natural immunity against HAV in Italy. HAV vaccine seems as safe in chronic liver
diseases than in general population. On the basis of the evidence we recommend
that subjects with chronic liver disease should be vaccinated against HAV,
especially if younger than 40 years.

Publication Types: 
    Review

PMID: 12744849 [PubMed - indexed for MEDLINE]

507: Vaccine. 2003 Jun 2;21(19-20):2234-7.

Hepatitis A: post-exposure prophylaxis.

Taliani G, Gaeta GB.

Clinica delle Malattie Infettive, Università di Firenze, Viale Morgagni 85, 50134
Firenze, Italy. talianig@ao-careggi.toscana.it

We report on the findings of an exploratory review of evidence published in
English from 1945 to identify the best post-exposure prophylaxis treatment and
the longest acceptable interval after exposure for prophylaxis to be effective.
We found no evidence that post-exposure administration of currently available
immunoglobulins is effective in preventing hepatitis A infection and disease. The
use of immunoglobulins for immunoprophylaxis should not be widely recommended
until a systematic review of the evidence has been conducted. We recommend that
active immunization to secondary contacts of exposed and vaccinated subjects be
offered.

Publication Types: 
    Review

PMID: 12744848 [PubMed - indexed for MEDLINE]

508: Vaccine. 2003 Jun 2;21(19-20):2224-33.

Risk groups for hepatitis A virus infection.

Franco E, Giambi C, Ialacci R, Coppola RC, Zanetti AR.

Department of Public Health, University of Rome Tor Vergata, Via Montpellier 1,
Rome 00133, Italy. franco@med.uniroma2.it

We report the conduct and results of a systematic search for evidence of risk of 
infection with hepatitis A virus (HAV) among blood transfusion recipients,
travellers, the military, healthcare workers, sewage workers, foodhandlers, day
care assistants, institutionalised subjects, blood transfusion recipients, drug
addicts, homosexuals, prisoners and other risk groups such a liver transplantees.
We report our recommendations for the use of the HAV vaccine in these groups.

Publication Types: 
    Review

PMID: 12744847 [PubMed - indexed for MEDLINE]

509: Clin Diagn Lab Immunol. 2003 May;10(3):492-4.

Anti-hepatitis A virus immunoglobulin M antibodies in urine samples for rapid
diagnosis of outbreaks.

Rodríguez Lay Lde L, Larralde Díaz O, Martínez Casanueva R, Gutiérrez Moreno A.

Institute for Tropical Medicine Pedro Kourí, Department of Virology, National
Reference Laboratory of Viral Hepatitis, Havana City, Cuba. licel@ipk.sld.cu

The main goal of this study was to test the feasibility of using urine for
diagnosing hepatitis A virus (HAV) infections. A correlation of 90.78% between
the test results of urine and serum samples was obtained. Four outbreaks of
hepatitis A were confirmed by testing only urine samples. The levels of anti-HAV 
immunoglobulin M (IgM) antibodies in urine samples remained stable during 6
months of storage at -70 degrees C but decreased when the samples were stored at 
4 degrees C. The results of tests of samples obtained 2 and 6 months after
infection suggested that IgM levels decline more rapidly in urine than in serum.

Publication Types: 
    Comparative Study

PMID: 12738658 [PubMed - indexed for MEDLINE]

510: Scand J Gastroenterol. 2003 Mar;38(3):307-13.

Hepatitis A virus VP3 may activate serum response element associated
transcription.

Kanda T, Yokosuka O, Kato N, Imazeki F, Fujiwara K, Kawai S, Saisho H, Omata M.

Dept. of Medicine and Clinical Oncology, Graduate School of Medicine, Chiba
University, Chiba, Japan.

BACKGROUND: Hepatitis A virus (HAV) infection is a major public health problem
worldwide. The infection does not induce any visible cytopathic effects or
interfere with macromolecular synthesis in host cells. However, the hepatitis B
and C viruses have recently been reported to activate intracellular signals. To
clarify the effects of HAV infection on intracellular signalling, we examined the
influence of 9 FLAG-tagged HAV proteins (VP2, VP3, VP1-2A, 2B, 2C, 3A, 3BC, 3C
and 3D) on signal transduction pathways. METHODS: Viral protein expression
vectors were co-transfected into HeLa cells with reporter plasmids controlled by 
a synthetic promoter containing direct repeats of the cyclic AMP response element
(CRE), serum response factor (SRF), activator protein 1 (AP-1), nuclear factor
kappaB (NF-kappaB) or serum response element (SRE). Cells were harvested 42 h
after transfection and luciferase assays were performed. Viral protein activation
twice that of the control was defined as significant. RESULTS: VP3 induced an
SRE-associated signal 2.2 +/- 0.3 times higher than that of control. VP3 did not 
activate CRE-, SRF-, AP-1- or NF-kappaB- associated signalling. The other HAV
proteins tested also failed to induce these pathways. CONCLUSIONS: HAV interacts 
with the host signalling mechanism, and HAV VP3, different from HBX and hepatitis
C core protein, may activate only SRE-associated intracellular signalling, a
pathway associated with cell proliferation and differentiation.

Publication Types: 
    Case Reports
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 12737447 [PubMed - indexed for MEDLINE]

511: Commun Dis Public Health. 2003 Apr;6(1):30-3.

Hepatitis A virus infection control: an audit of practice in England and Wales
prior to guidelines being published.

Markov PV, Ahmed SN, Crowcroft NS.

Health Protection Agency, Immunisation Division, Communicable Disease
Surveillance Centre, 61 Colindale Avenue, London NW9 5EQ.

This survey was conducted in September 2001 to audit the practice of Consultants 
in Communicable Disease Control (CsCDC) and to gain a systematic picture of
pre-guideline approaches to the control of hepatitis A virus infection in England
and Wales. An audit form was distributed to all CsCDC by email and responses were
entered in a database and analysed. Response rate is estimated at 44%. CsCDC
predominantly recommend vaccination for prevention. For 31% of the CsCDC, index
cases were not reported within a week of the onset of illness. As a result,
vaccine was often used sub-optimally. By contrast 95% of the CsCDC were informed 
of an index case within two weeks of onset of illness, in time for effective use 
of human normal immunoglobulin (HNIG). CsCDC were cautious in the use of HNIG for
a number of reasons including concerns about variant Creutzfeldt-Jacob Disease
(vCJD). A substantial proportion (between 5% and 28% for different age groups) of
CsCDC did not recommend any active prevention among close family contacts of a
case. Important ways to improve practice include facilitating use of HNIG and
speeding up reporting by doctors and laboratories.

PMID: 12736969 [PubMed - indexed for MEDLINE]

512: Commun Dis Public Health. 2003 Apr;6(1):26-9.

Comment in:
    Commun Dis Public Health. 2003 Sep;6(3):259.

Management of hepatitis A in a food handler at a London secondary school.

Nicholls M, Bruce M, Thomas J.

Chemical Incident Response Service, Medical Toxicology Unit, Avonley Road, London
SE14 5ER. margot@btclick.com

A case of hepatitis A in a food handler at a local secondary school prompted the 
institution of control measures including administration of human normal
immunoglobulin (HNIG) to all pupils. This paper summarises the management of the 
incident and describes the use of HNIG to prevent secondary cases. Few adverse
effects were reported and only one secondary case of hepatitis A occurred at the 
school.

Publication Types: 
    Case Reports

PMID: 12736968 [PubMed - indexed for MEDLINE]

513: Indian Pediatr. 2003 Apr;40(4):328-31.

Prevalence of antibodies to hepatitis A and hepatitis E virus in urban school
children in Chennai.

Mohanavalli B, Dhevahi E, Menon T, Malathi S, Thyagarajan SP.

Department of Microbiology, Dr. A.L. Mudaliar Post Graduate Institute of Basic
Medical Sciences, Taramani, Chennai 600 113, India.

With similar feco-oral mode of transmission of Hepatitis A and E viruses, and
improving levels of personal hygiene among higher socioeconomic population,
periodic surveillance on HAV/HEV exposure pattern may be of immense public health
value. One such attempt was made in Tamilnadu, India by analysing the presence of
antibodies to HAV and HEV in 185 healthy children of 6 months to 12 years of age.
While anti HAV positivity was 96.9% by 12 years of age, anti HEV positivity
fluctuated between 5.3-16.7%. The study suggests the necessity for developing a
vaccine for HEV to prevent the frequent occurrence of HEV outbreaks in India,
since natural HEV exposure does not bestow significant protection as observed in 
HAV.

Publication Types: 
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 12736405 [PubMed - indexed for MEDLINE]

514: J Travel Med. 2003 Jan-Feb;10(1):11-4.

Immunity to hepatitis A in people born and raised in endemic areas.

Barnett ED, Holmes AH, Geltman P, Phillips SL, Harrison TS.

International Clinic, Boston Medical Center, Massachusetts, USA.

BACKGROUND: Hepatitis A is the most common vaccine-preventable disease in
international travelers. Many individuals born and raised in hepatitis A endemic 
areas are likely to be immune to hepatitis A. Unnecessary hepatitis A
immunization could be avoided by taking into account prior exposure to hepatitis 
A and judicious use of serotesting prior to immunization. METHODS: Patients born 
and raised in countries of high prevalence of hepatitis A who were seen for
pretravel consultation and who had hepatitis antibody measured were eligible.
Data were collected about country of birth and length of residence there before
emigration, length of time till departure on current trip, current age, and
hepatitis A antibody result. RESULTS: Patients ranged from 12 to 74 years of age 
and were from 27 countries. Their pretravel visit occurred from 4 to more than 90
days prior to departure. Ninety-five percent (122 of 129) of patients were immune
to hepatitis A, including 100% (83 of 83) of those who resided in their country
of origin until at least aged 20. Most patients were seen for pretravel
consultation less than 28 days prior to departure. CONCLUSION: Individuals born
and raised until aged 20 in hepatitis A endemic countries are likely to be immune
to hepatitis A. Serotesting is most helpful in assessing immunity to hepatitis A 
in those under 20 years of age.

PMID: 12729507 [PubMed - indexed for MEDLINE]

515: J Travel Med. 2003 Jan-Feb;10(1):4-10.

A population-based comparison between travelers who consulted travel clinics and 
those who did not.

Duval B, De Serre G, Shadmani R, Boulianne N, Pohani G, Naus M, Rochette L,
Fradet MD, Kain KC, Ward BJ.

Institut National de Santé Publique du Québec, Canada.

BACKGROUND: Travel to hepatitis A-endemic countries is frequent among North
Americans. Such travel carries significant risks for the individuals themselves
and for the general population. We documented the patterns of use of travel
clinics in a large Canadian adult population. METHODS: Travelers who had visited 
a hepatitis A-endemic country between 1990 and the time of the survey in 1999
were eligible. Subjects were identified from a representative sample of 4,002
adults from the two largest Canadian provinces. They were contacted by random
digit dialing and interviewed by telephone. RESULTS: Only 15% of trips had been
preceded by a visit to a travel clinic. The probability of visiting a travel
clinic was approximately 10 times greater for travelers considered to be in the
high-risk category than for those in the low-risk category, but the former
represented only 2% of the total. The probability of visiting a travel clinic was
approximately 23 times greater for travelers who were aware of the health risks
in their country of destination. Income level was not associated with attendance 
at a travel clinic, and cost was rarely mentioned as a reason for not attending
such a travel clinic before departure. CONCLUSIONS: Each year, millions of
Canadian travelers go to hepatitis A-endemic countries without consulting a
travel clinic. Active steps must be taken by public health authorities to improve
their utilization of health services and prevent the accrued health risk for
these travelers.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 12729506 [PubMed - indexed for MEDLINE]

516: Keio J Med. 2003 Mar;52(1):38-51.

Hemophagocytic syndrome associated with fulminant hepatitis A: a case report.

Ishii H, Yamagishi Y, Okamoto S, Saito H, Kikuchi H, Kodama T.

Department of Internal Medicine, School of Medicine, Keio University, Tokyo,
Japan.

A 37-year-old man had a sore throat and pyrexia since January 1999. He was
treated at a nearby hospital, but not improved. Jaundice was indicated there, and
the patient was referred transferred to our hospital, where he was admitted for
treatment with a diagnosis of severe acute hepatitis with acute renal failure.
Thereafter the patient was revealed to have had a past history of heavy drinking,
and he underwent the treatment with a diagnosis of acute fulminant hepatitis due 
to hepatitis A virus (HAV). He showed a tendency toward improvement. During the
course, however, viral associated hemophagocytic syndrome (VAHS) developed.
Various treatments were conducted, but it was not improved, and the patient died 
on Hospital Day 66. On pathologic autopsy, remarkable hepatosplenomegaly
associated with marked bone marrow abnormalities compatible with VAHS was
observed. Aspergillus abscesses were also observed in many organs, and they were 
considered as an adverse reaction to potent immunosuppressive therapy. Since
there have been only a few reports on HAV-related VAHS, discussing VAHS related
to HAV, the present case was considered valuable.

Publication Types: 
    Case Reports
    Clinical Conference

PMID: 12713021 [PubMed - indexed for MEDLINE]

517: FEBS Lett. 2003 Apr 10;540(1-3):133-40.

Liposome entrapment and immunogenic studies of a synthetic lipophilic multiple
antigenic peptide bearing VP1 and VP3 domains of the hepatitis A virus: a robust 
method for vaccine design.

Haro I, Pérez S, García M, Chan WC, Ercilla G.

Departament de Química de Pèptids i Proteïnes, IIQAB-CSIC, Jordi Girona 18-26,
08034 Barcelona, Spain. ihvqpp@iiqab.csic.es

Multiple antigen peptides (MAP) have been demonstrated to be efficient
immunological reagents for the induction of immune responses to a variety of
infectious agents. Several peptide domains of the hepatitis A virus (HAV) capsid 
proteins, mainly VP1 and VP3, are the immunodominant targets for a protective
antibody response. In the present study we analyse the immunogenic properties of 
a tetrameric heterogeneous palmitoyl-derivatised MAP containing two defined HAV
peptide sequences, VP1(11-25) and VP3(102-121), in rabbits immunised with either 
Freund's adjuvant or multilamellar liposomes. The immune response was evaluated
with a specific enzyme immunoassay using MAP[VP1+VP3], VP1 and VP3 as targets.
The avidity of the immune response was measured by a non-competitive
enzyme-linked immunosorbent assay and by the surface plasmon resonance
technology. Antisera raised against the lipo-MAP peptide entrapped in liposomes
demonstrated high avidity of binding with affinity rate constants approximately
one order of magnitude greater than those obtained with the Freund's protocol.
Copyright 2003 Federation of European Biochemical Societies

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12681496 [PubMed - indexed for MEDLINE]

518: J Med Virol. 2003 Jun;70(2):187-93.

Sequential changes in hepatitis A virus genotype distribution in Estonia during
1994 to 2001.

Tallo T, Norder H, Tefanova V, Ott K, Ustina V, Prukk T, Solomonova O, Schmidt J,
Zilmer K, Priimägi L, Krispin T, Magnius LO.

Department of Virology, Estonian Institute of Experimental and Clinical Medicine,
Tallinn, Estonia.

Hepatitis A virus (HAV) isolates from a large outbreak and from non-outbreak
cases in Estonia were characterized by sequencing the aminoterminal VP1 region.
From January 1998 to December 1999, a total of 1084 cases of hepatitis A were
reported to the Harjumaa-Tallinn and Ida-Virumaa Health Protection Services in
Estonia. The attack rate was highest among males aged 15-29. Initial cases were
noted to be associated with injecting drug use. IgM anti-HAV positive sera were
available from 107 hospitalized outbreak cases and from 68 patients sampled
during 1994 to 2001. HAV RNA was detected in 42% of sera from 1994-1996 and in
88% of sera from 1998-2001. It was possible to obtain HAV sequences from 83
outbreak and 29 background cases. The outbreak strain was represented by five
different sequences, all belonging to subtype IIIA. During the outbreak, this
IIIA strain also spread into the general population. All available non-outbreak
isolates from 1994 to 2001 but one belonged to genotype IA and formed distinct
clusters as compared to isolates from other parts of the world. One subtype IIIA 
isolate from 1995 was unrelated to the outbreak strain. Subtype IA had been
dominating in Estonia during 1994-2001, but the outbreak strain from 1998 to 1999
was IIIA. This subtype was encountered previously in addicts in Sweden during the
1980s and in Norway at the end of the 1990s. This study supports the use of
limited sequencing within the aminoterminal VP1 region for studying the molecular
epidemiology of hepatitis A. Copyright 2003 Wiley-Liss, Inc.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12696104 [PubMed - indexed for MEDLINE]

519: J Infect Dis. 2003 Apr 15;187(8):1327-31. Epub 2003 Mar 24.

Safety and immunogenicity of hepatitis A vaccine in human immunodeficiency
virus-infected patients: a double-blind, randomized, placebo-controlled trial.

Kemper CA, Haubrich R, Frank I, Dubin G, Buscarino C, McCutchan JA, Deresinski
SC; California Collaborative Treatment Group.

Division of Infectious Diseases, Department of Medicine, Santa Clara Valley
Medical Center, San Jose, California, USA. cakemper@earthlink.net

The safety and immunogenicity of inactivated hepatitis A (HepA) vaccine was
assessed in 133 hepatitis A virus-seronegative, human immunodeficiency virus
(HIV)-infected adults. Patients were randomly assigned to receive, in a blinded
fashion, either 2 doses of vaccine (1440 enzyme-linked immunosorbent assay units)
or placebo 6 months apart. Seroconversion at month 9 was observed in 68% of those
with CD4 cell counts >/=200 cells/mm(3) but in only 9% of those with lower CD4
cell counts (P=.004). HepA vaccine was well tolerated and had no effect on the
course of HIV infection or plasma HIV RNA load.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 12696015 [PubMed - indexed for MEDLINE]

520: J Infect Dis. 2003 Apr 15;187(8):1235-40. Epub 2003 Mar 26.

Outbreak of hepatitis A among men who have sex with men: implications for
hepatitis A vaccination strategies.

Cotter SM, Sansom S, Long T, Koch E, Kellerman S, Smith F, Averhoff F, Bell BP.

Division of Viral Hepatitis, National Center for Infectious Diseases, Centers for
Disease Control and Prevention, Atlanta, Georgia 30333, USA.

Between November 1998 and May 1999, 136 cases of hepatitis A were reported in
Columbus, Ohio. Eighty-nine (65%) case patients were reinterviewed. Of 74 male
case patients, 47 (66%) were men who have sex with men (MSM). These 47 MSM were
compared with 88 MSM control subjects, to identify risk factors for infection and
potential opportunities for vaccination. During the exposure period, 6 (13%) case
patients reported contact with a person who had hepatitis A, compared with 2 (2%)
control subjects (odds ratio, 6.15; 95% confidence interval, 1.04-48.02); neither
number of sex partners nor any sex practice was associated with illness. Most
case patients and control subjects (68% and 77%, respectively) saw a health care 
provider at least annually, and 93% of control subjects reported a willingness to
receive hepatitis A vaccine. MSM are accessible and amenable to vaccination;
increased efforts are needed to provide vaccination, regardless of reported sex
practices.

PMID: 12696002 [PubMed - indexed for MEDLINE]

521: Pediatr Infect Dis J. 2003 Apr;22(4):354-9.

Hepatitis A vaccination of infants: effect of maternal antibody status on
antibody persistence and response to a booster dose.

Fiore AE, Shapiro CN, Sabin K, Labonte K, Darling K, Culver D, Bell BP, Margolis 
HS.

Division of Viral Hepatitis, Centers for Disease Control and Prevention, Mailstop
G37, 1600 Clifton Road, Atlanta, GA 30333, USA. afiore@cdc.gov

BACKGROUND: Infants with passively transferred maternal antibody (PMA) to
hepatitis A virus (HAV) have lower concentrations of antibody to HAV (anti-HAV)
after vaccination. We examined the effect of PMA on persistence of anti-HAV and
on immune memory. METHODS: We measured anti-HAV concentrations of 6-year-old
children who had responded to a three dose hepatitis A vaccine series at ages 2, 
4 and 6 months. Group 1 children were born to anti-HAV-negative women; Group 2
children had anti-HAV-positive mothers and PMA at 2 months of age. Children
without detectable antibody at 6-year follow-up were offered a booster dose [360 
enzyme-linked immunosorbent units (ELU)]. An anamnestic response was defined as a
postbooster anti-HAV concentration of > or =400 mIU/ml. RESULTS: At follow-up,
before the booster dose, Group 1 subjects had a higher geometric mean
concentration (50 mIU/ml vs.18 mIU/ml, P = 0.007), and a larger proportion
retained seroprotective concentrations of anti-HAV [21 of 31 (68%) vs.4 of 17
(24%)] compared with Group 2 subjects. The two stage antibody decline curves for 
the two groups from 8 months old to follow-up testing were parallel. An
anamnestic response occurred in all (5 of 5) Group 1 and 67% (4 of 6) of Group 2 
children. The geometric mean antibody concentrations after the booster were 1102 
and 406 mIU/ml for Groups 1 and 2, respectively (P = 0.10). CONCLUSIONS: Infants 
with PMA who receive hepatitis A vaccine have significantly lower concentrations 
of anti-HAV 6 years later than infants with no PMA who receive hepatitis A
vaccine. Immune memory may remain functional despite these lower anti-HAV
concentrations.

Publication Types: 
    Comparative Study
    Research Support, U.S. Gov't, P.H.S.

PMID: 12690277 [PubMed - indexed for MEDLINE]

522: Infection. 2003 Mar;31(2):70-4.

Comment in:
    Infection. 2003 Mar;31(2):69.

Prevalence rates of viral hepatitis infections in refugee Kurds from Iraq and
Turkey.

Chironna M, Germinario C, Lopalco PL, Carrozzini F, Barbuti S, Quarto M.

Dept. of Internal Medicine and Public Health, Hygiene Section, University of
Bari, Policlinico, Piazza G. Cesare 11, I-70124 Bari, Italy.
m.chironna@igiene.uniba.it

BACKGROUND: Since little is known about the burden of viral hepatitis in Kurds,
the prevalence of infection with hepatitis A virus (HAV), hepatitis E virus
(HEV), hepatitis B virus (HBV) and hepatitis C virus (HCV) was investigated in a 
sample of refugee Kurds from Iraq and Turkey. PATIENTS AND METHODS: A
cross-sectional study was carried out. Serological markers to hepatitis viruses
were determined for 1,005 subjects from all age-groups of which 36.6% were from
Turkey and 63.4% from Iraq. RESULTS: Overall seroprevalence for anti-HAV was
94.4% and 14.8% for anti-HEV. A significantly higher prevalence for anti-HEV was 
found among Iraqis (17.5%) compared to Turkish immigrants (10.0%). The prevalence
of hepatitis B surface antigen (HBsAg) and total anti-HBc (core) was 6.8% and
35.6% in Turkish Kurds and 2.2% and 12.7% in Iraqis, respectively. Only 10% of
children aged up to 10 years and 2.8% of subjects aged 11-20 years had been
vaccinated against HBV, the majority of them coming from Iraq. One subject was
confirmed as positive for anti-HCV (0.1%) and HCV-RNA and analysis showed a 4c/4d
genotype. CONCLUSION: This survey shows a high prevalence of enterically
transmitted viral hepatitis in Kurds. HBV infection is moderately endemic, while 
the prevalence of HCV infection is low. There is a need for a universal
immunization strategy for HBV in the Kurd population.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12682810 [PubMed - indexed for MEDLINE]

523: Transfusion. 2003 Apr;43(4):536-40.

Comment in:
    Transfusion. 2004 Jul;44(7):1121-2.

Transmission of hepatitis A via WBC-reduced RBCs and FFP from a single donation.

Diwan AH, Stubbs JR, Carnahan GE.

Department of Pathology, University of South Alabama Medical Center, 2451
Fillingim Street, Mobile, AL 36617, USA.

BACKGROUND: Currently, individuals donating whole blood and cellular components
are not screened for hepatitis A (HA). However, transfusion-transmitted HA can
occur, albeit very rarely. Although infection is typically mild and self-limited,
it may be catastrophic in a small percentage of cases. Two cases of HA
transmission from a single donation to two patients with subsequent variable
morbidity are reported. CASE REPORTS: A 50-year-old, asymptomatic, volunteer
blood donor made a whole-blood donation. He was found to have HA 18 days later.
When notified, the donor center initiated a recall of the components produced
from the donated unit. However, the RBCs and FFP had already been transfused.
Subsequently, both recipients developed HA as documented by IgM anti-HA serology.
The RBC recipient was a 49-year-old woman, transfused after a hysterectomy, who
was found to have HA at the time of unit recall (20 days after transfusion). Her 
condition required the use of medical disability leave. The FFP was infused to a 
52-year-old female cardiac surgical patient. Her course was marked by multiple
complications, including postoperative development of mild hepatic dysfunction.
After testing negative for HA, hepatitis B, and hepatitis C (24 days after
transfusion), she suffered a second bout of more severe hepatic dysfunction and
was documented to have HA at Day 55 after transfusion. Evaluation of both
recipients' close contacts revealed no evidence for exposure to HA by any route
other than transfusion. CONCLUSION: HA can be transmitted by transfusion of units
obtained from asymptomatic, infectious donors. Two patients contracted HA from
components obtained from a single whole-blood donation. The RBC recipient had a
typical self-limited course of HA. The FFP recipient developed HA of relatively
delayed onset. Both recovered from HA.

Publication Types: 
    Case Reports

PMID: 12662288 [PubMed - indexed for MEDLINE]

524: Trop Gastroenterol. 2002 Apr-Jun;23(2):76-8.

Epidemiology of hepatitis E and A in Ludhiana.

Kaur H, Oberoi A, Chander R, Pawar G, Verma M.

Christian Medical College, Ludhiana, Punjab-141 008.

AIM: To study the epidemiology of hepatitis E and A in Ludhiana. METHODS: A
retrospective analysis of laboratory data of the year 2001 was done, to study the
epidemiology of hepatitis E and A in Ludhiana in relation to prevalence, age,
sex, area of residence and seasonal variation. RESULTS: Prevalence of HEV was
13.9%. Infection with it occurred through out the year with no preponderance of
cases following the monsoons. Young male adults between 20-40 years of age were
predominantly affected. Prevalence of HAV was 5.5% affecting mainly children
below 14 years of age. Population of urban areas around "Gandha Naliash" (a large
open sewer) was at high risk as there was clustering of HEV & HAV cases around
that area.

PMID: 12632974 [PubMed - indexed for MEDLINE]

525: Acta Paediatr Taiwan. 2002 Nov-Dec;43(6):358-60.

Relapsing hepatitis A in children: report of two cases.

Arslan S, Caksen H, Oner AF, Odabaş D, Rastgeldi L.

Department of Pediatrics, Yüzüncü Yil University Faculty of Medicine, Van,
Turkey.

Viral A hepatitis is a self-limited infection occurring predominantly among
children usually as an anicteric often subclinical illness. After a stage of
typical hepatitis A, a biphasic or relapsing form of viral hepatitis A (R-HA) may
occur. Although relapse occurs in 3 to 21% of patients with acute hepatitis A,
the patients with R-HA have been unusually reported in the literature. In this
article, we report two children with R-HA because of unusual presentation and to 
draw attention to the importance of R-EA.

Publication Types: 
    Case Reports

PMID: 12632793 [PubMed - indexed for MEDLINE]

526: Euro Surveill. 2002 Apr;7(4):61-5.

Laboratory capability in Europe for foodborne viruses.

Lopman B, van Duynhoven Y, Hanon FX, Reacher M, Koopmans M, Brown D; Consortium
on Foodborne Viruses in Europe.

Public Health Laboratory Service, Colindale, London, England.

This report describes a survey of national laboratory capabilities of diagnostics
and surveillance databases for foodborne viruses among the "Foodborne Viruses in 
Europe" consortium. All the countries have laboratories that can test for HAV
antibody in human serum. Eight of the ten surveyed European countries maintain a 
national database of HAV cases. Food can be tested for the presence of HAV in
Finland, Italy, Spain, France and Denmark. All surveyed countries have at least
one laboratory that tests for Norwalk-like virus (NLV) by reverse
transcriptase-polymerase chain reaction and all also have the capability to use
electron microscopy. Five countries maintain a national database of NLV cases and
nine maintain a national database of NLV outbreaks. Almost all participant
countries have laboratories that can test for NLV in food items including
shellfish.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12631939 [PubMed - indexed for MEDLINE]

527: Trans R Soc Trop Med Hyg. 2002 Nov-Dec;96(6):605-10.

The intensity of transmission of hepatitis A and heterogeneities in
socio-environmental risk factors in Rio de Janeiro, Brazil.

de Almeida LM, Amaku M, Azevedo RS, Cairncross S, Massad E.

Núcleo de Estudos de Saúde Coletiva, Universidade Federal do Rio de Janeiro, Av. 
Brig. Trompowski, s/n, HUCFF, 5o andar/Ala Sul, sala 25, Ilha do Fundão,
21941-590 Rio de Janeiro, RJ, Brazil.

The objective of this work was to assess the intensity of transmission of
hepatitis A in Rio de Janeiro, Brazil. We also used the estimation of the
parameters of a deterministic model to study the effects of risk factors.
Age-specific seroprevalence of antibodies against hepatitis A virus (HAV) was
obtained from a survey screening in a city of the metropolitan area of Rio de
Janeiro, in 1997. From the seroprevalence data, we estimated the age-dependent
force of infection (lambda) and the average age of first infection (A), using a
deterministic model. To evaluate the influence of the environmental risk factors,
we estimated the same parameters stratifying the sample for the selected
socio-environmental risk factors: the number of years of schooling of the female 
responsible for the house, crowding within the bedroom, number of water taps and 
fittings, and the presence of sewage in front of the house. For the whole sample,
the maximum force of infection estimated was 0.12/year and the average age of
infection was 10.1 years. This last parameter decreased as the number of persons 
per bedroom increased, and also when the number of water taps and the number of
years of schooling of the woman responsible for the house decreased. The proposed
environmental interventions may lead to a decrease in the intensity of
transmission of HAV and an increase in the average age of first infection in the 
next few years. This may have public health implications, since hepatitis A is
more severe in adults. In this context, specific vaccination programmes may be
necessary, as in developed countries.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12625132 [PubMed - indexed for MEDLINE]

528: Indian J Pediatr. 2003 Jan;70(1):73-9.

Acute liver failure.

Arora NK, Mathur P, Ahuja A, Oberoi A.

Division of Pediatric Gastroenterology, Hepatology & Nutrition, Department of
Pediatrics, All India Institute of Medical Sciences, New Delhi, India.
nkmanan@hotmail.com

Acute liver failure in children is associated with a high mortality. Most cases
in our setup are due to water borne hepatotropic viruses HAV and HEV. The
clinician must be aware of the earliest and the subtle signs of acute liver
failure to identify cases early enough and institute supportive therapy. Focus of
therapy has to be on prevention, early recognition and appropriate management of 
complications. Despite good intensive care, about 40-60% children with liver
failure die. As and when liver transplantation becomes available in India, it
would be an attractive option.

Publication Types: 
    Review

PMID: 12619956 [PubMed - indexed for MEDLINE]

529: J Paediatr Child Health. 2003 Mar;39(2):83-7.

Hepatitis A vaccination options for Australia.

MacIntyre CR, Burgess MA, Hull B, McIntyre PB.

National Centre for Immunisation Research and Surveillance of Vaccine Preventable
Diseases, Children's Hospital at Westmead, Westmead and University of Sydney, New
South Wales, Australia. RainaM@chw.edu.au

The epidemiology of hepatitis A is changing, with an increasing proportion of the
population becoming susceptible to infection. The burden of hepatitis A is
comparable to that of other vaccine-preventable diseases for which new vaccines
are available. Options for vaccination include selective programmes for high-risk
groups, which could involve screening prior to vaccination, or universal
programmes for infants and/or adolescents. Selective programmes have been shown
to be highly cost-effective if well implemented, but there is evidence that they 
might be poorly implemented. If a universal vaccination programme were considered
for Australia, an infant programme, with doses at 18 months and 2 years, possibly
with an additional adolescent programme, would be the recommended option.
Universal hepatitis A vaccination for infants and/or adolescents is of comparable
cost-effectiveness compared with other preventive strategies, but needs to be
considered in the context of competing vaccination options.

Publication Types: 
    Review

PMID: 12603793 [PubMed - indexed for MEDLINE]

530: Am J Gastroenterol. 2003 Feb;98(2):448-53.

Viral hepatitis-related acute liver failure.

Schiødt FV, Davern TJ, Shakil AO, McGuire B, Samuel G, Lee WM.

Department of Gastroenterology, Rigshospitalet, Copenhagen, Denmark.

OBJECTIVES: Viral hepatitis has previously been the major cause of acute liver
failure (ALF) in the United States. We aimed to determine the incidence of viral 
hepatitis-related ALF and to compare the outcome and clinical and biochemical
variables in patients with hepatitis A and B. METHODS: A total of 354 patients
with ALF from multiple centers were screened for possible acute viral etiology.
RESULTS: Forty-three patients (12.1% of all ALF cases) had acute viral hepatitis:
hepatitis A (n = 16), hepatitis B (n = 26), and herpes simplex virus infection (n
= 1). There was no difference between groups with regard to age, gender, body
mass index, admission or peak coma grade, symptom duration, admission mean
arterial pressure, temperature, or biochemical liver tests, creatinine, arterial 
pH, or rate of infections. Platelet count was significantly higher in hepatitis A
patients than in hepatitis B patients. The transplantation-free (spontaneous)
survival rate was significantly higher for hepatitis A patients (69%) than for
hepatitis B patients (19%, p = 0.007), whereas the liver transplantation rate was
higher in hepatitis B patients (62%) than in hepatitis A patients (19%, p =
0.017). Spontaneous survivors had significantly higher mean arterial pressure,
higher platelet count, and lower AST/ALT ratio than patients who did not survive 
spontaneously. CONCLUSIONS: Viral hepatitis now comprises only one-eighth of all 
ALF cases in the United States. The marked difference in spontaneous survival
between hepatitis A and B cannot be explained by the severity of hepatic
dysfunction on admission but may rather be an inherent feature of the infections 
or a bias toward transplanting patients with hepatitis B.

Publication Types: 
    Multicenter Study
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 12591067 [PubMed - indexed for MEDLINE]

531: Med Hypotheses. 2003 Mar;60(3):337-9.

Does infection with hepatitis A virus provide protection against hepatitis E
virus?

Syed SA, Sarwari AR, Smego RA Jr, Hamid S, Nissa T.

The Aga Khan University Medical College, Karachi, Pakistan.

Hepatitis A virus (HAV) and hepatitis E virus (HEV) share some common
epidemiologic features, but the dramatic age-related difference in their disease 
prevalences suggests that the immune response to HAV may provide some
cross-protection against HEV.

PMID: 12581608 [PubMed - indexed for MEDLINE]

532: Folia Med (Plovdiv). 2002;44(3):11-4.

A study on the basic epidemiological parameters of viral hepatitis a in the
region of Plovdiv, Bulgaria.

Rakadjieva T, Stoilova J, Petrov A.

Department of Infectious Diseases, Epidemiology and Parasitology, Medical
University, Plovdiv, Bulgaria.

INTRODUCTION: Infection with hepatitis A virus is of great importance to public
health. The disease has a worldwide occurrence due to inadequate sanitation and
the variable seroprevalence rates in the community. OBJECTIVE: The present report
investigates the epidemiological features of hepatitis A in the region of Plovdiv
and outlines the most important epidemiological features of the disease.
MATERIALS AND METHODS: In 1999 (a year with a lower hepatitis A prevalence) the
basic epidemiological characteristics of the disease were studied: overall
morbidity and mortality rates, age, sexual and seasonal distribution, and
prevalence in rural and urban areas. The study was carried out in a cohort of 288
patients with hepatitis A admitted to the Clinic of Infectious Disease of the
Medical University in Plovdiv. All patients were anti HAV IgM positive. Routine
clinical, laboratory, epidemiological and statistical methods were used.
Laboratory and serological tests were performed at the Center for Disease
Control, Plovdiv and at the University Clinical Laboratory. RESULTS: Of 423
patients with acute viral hepatitis 288 (68.09%) had hepatitis A. In 1999 the
morbidity rate for the region of Plovdiv was 49.55 per hundred thousand
(intermediate). Disease prevalence was the highest in preschool and early school 
age as well as in the age groups 20-29 (84.67 per hundred thousand) and 30-39
(71.59 per hundred thousand). Urban residents accounted for 79.85% of the cases. 
The male/female ratio was 1:1. 82.25% of the preschool children did not attend
day-care centers. History of contact with sources of infection was elicited from 
17.01% of the patients. Disease rates peaked in October through December (maximum
in October). CONCLUSIONS: Accumulated data could contribute to more effective
disease control.

PMID: 12580524 [PubMed - indexed for MEDLINE]

533: Am J Ind Med. 2003 Feb;43(2):172-8.

Prevalence of hepatitis A virus infection among sewage workers in Georgia.

Venczel L, Brown S, Frumkin H, Simmonds-Diaz J, Deitchman S, Bell BP.

Division of Viral Hepatitis, National Center for Infectious Diseases, Centers for
Disease Control and Prevention, Atlanta, GA 30333, USA.

BACKGROUND: Wastewater (WW) workers could have opportunity for direct contact
with raw sewage, which might contain hepatitis A virus (HAV). METHODS: A
serologic survey of WW workers and a comparison population of roads and drainage 
workers (RD). Factors potentially associated with anti-HAV positivity were
evaluated in univariate and multivariate analyses. RESULTS: Among the 365 WW
workers, overall anti-HAV prevalence was 38%, similar to that (35%) of the 166 RD
workers (P = 0.5). Prevalence varied by wastewater job type from 45% among the
164 field crew workers to 32% among the 201 treatment plant workers. In
multivariate modeling, factors associated with anti-HAV positivity included age >
or = 40 years (odds ratio [OR] = 2.4; 95% CI = 1.6-3.7), black compared to other 
races (OR = 2.4; 95% CI = 1.5-3.8), birth outside the United States (OR = 7.5;
95% CI = 3.0-18.6), a high school education or less (OR 2.1; 95% CI = 1.4-3.2)
and work on the field crew compared to RD work (OR 1.6; 95% CI = 1.1-2.4).
CONCLUSIONS: These results are consistent with no or a small increased risk of
hepatitis A among WW workers, and do not provide a clear mandate for hepatitis A 
vaccination of these workers. Am. J. Ind. Med. 43: 172-178, 2003. Copyright 2003 
Wiley-Liss, Inc.

Publication Types: 
    Comparative Study

PMID: 12541272 [PubMed - indexed for MEDLINE]

534: Circulation. 2003 Jan 21;107(2):251-7.

Comment in:
    Circulation. 2003 Jan 21;107(2):220-2.    Circulation. 2003 Jul 8;108(1):e8.

Multiple infections and subsequent cardiovascular events in the Heart Outcomes
Prevention Evaluation (HOPE) Study.

Smieja M, Gnarpe J, Lonn E, Gnarpe H, Olsson G, Yi Q, Dzavik V, McQueen M, Yusuf 
S; Heart Outcomes Prevention Evaluation (HOPE) Study Investigators.

Department of Pathology and Molecular Medicine, McMaster University, Hamilton,
Ontario, Canada.

BACKGROUND: Limited prospective epidemiological data are available on the
relation between exposure to Chlamydia pneumoniae, Helicobacter pylori,
cytomegalovirus (CMV), and hepatitis A virus (HAV), individually or as a total
pathogen score, and human cardiovascular (CV) disease. METHODS AND RESULTS: We
analyzed enrollment sera from 3168 Canadian patients in the Heart Outcomes
Prevention Evaluation (HOPE) study for antibodies to C pneumoniae, H pylori, CMV,
and HAV and measured the relation between serostatus and 494 adjudicated trial
outcomes of myocardial infarction, stroke, or CV death over 4.5 years of
follow-up. CV events were associated with CMV serostatus (covariate-adjusted
hazard ratio [HR], 1.24; 95% CI, 1.01, 1.53). Neither C pneumoniae IgG (adjusted 
HR, 0.87; 95% CI, 0.68, 1.10), C pneumonia IgA (adjusted HR, 1.10; 95% CI, 0.90, 
1.34), H pylori IgG (HR, 0.99; 95% CI, 0.82, 1.19), nor HAV IgG (HR, 1.01; 95%
CI, 0.83, 1.24) predicted CV events. Total pathogen score was associated with CV 
events (adjusted HR for 4 versus 1 or 0=1.41; 95% CI, 1.02, 1.96). CONCLUSIONS:
Exposure to CMV but not to C pneumoniae, H pylori, or HAV was associated with a
slight excess risk of subsequent myocardial infarction, stroke, or CV death in
HOPE study patients, and total pathogen score based on these infections predicted
a small increased hazard of CV events.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12538424 [PubMed - indexed for MEDLINE]

535: Ann Trop Med Parasitol. 2002 Oct;96(7):727-34.

Molecular characterization of hepatitis-A-virus infections, in the context of two
outbreaks in southern Thailand.

Theamboonlers A, Jantaradsamee P, Chatchatee P, Chongsrisawat V, Mokmula M,
Poovorawan Y.

Viral Hepatitis Research Unit, Paediatric Department, Faculty of Medicine,
Chulalongkorn University and Hospital, Rama IV Road, Bangkok 10330, Thailand.

As hepatitis A virus (HAV) is usually transmitted through the faecal-oral route, 
hepatitis A is a communicable disease. In countries of intermediate to low
endemicity, sudden outbreaks of human infection with the virus may occur. Between
September 2001 and April 2002, there were two outbreaks of HAV infection in the
Ruso and Yeengor districts of Narathiwas province, in southern Thailand. Isolates
of HAV were recovered during these outbreaks, from 14 in-patients with acute
hepatitis in Ruso (12 positive for anti-HAV IgM and all positive for HAV RNA), 16
children with asymptomatic infection in Yeengor (14 positive for anti-HAV IgM and
nine for HAV RNA), and four isolated cases in Bangkok (all positive for anti-HAV 
IgM). Molecular characterization of the VP1-P2A region of each isolate was
followed by phylogenetic analysis. All of the isolates from Narathiwas province
were found to be of genotype 1a, to have the same VP1 nucleotide sequence, and to
show a high level of sequence homology (>/= 99.5%) with the isolates from Bangkok
and with previous Thai isolates. These results should facilitate further research
into HAV transmission and genotype identification in community outbreaks.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12537634 [PubMed - indexed for MEDLINE]

536: Vaccine. 2003 Jan 30;21(7-8):698-701.

Effectiveness of a mass hepatitis A vaccination program in preadolescents.

Domínguez A, Salleras L, Carmona G, Batalla J.

Department of Health and Social Security, General Directorate of Public Health,
Generalitat of Catalonia, Travessera de les Corts, 131-159, 08028, Barcelona,
Spain. angelad@dsss.scs.es

A program of mass hepatitis A+B vaccination in preadolescents in schools was
begun in the Catalonia in the last quarter of 1998. This study investigated the
impact of the program by comparing the incidence of hepatitis A in vaccinated and
unvaccinated cohort.The greatest reduction of the incidence rate of hepatitis A
was observed in the 10-14 years age group, from 10.3 per 100000 persons-year in
the period 1996-1998 to 1.8 per 100000 persons-year in the period 1999-2001. The 
global incidence decreased from 6.2 to 2.6 per 100000 persons-year.After analysis
of cases occurring in the vaccinated and non vaccinated cohort, the effectiveness
of the vaccination program was estimated at 97.0% (95% CI: 78.6-99.6).

PMID: 12531343 [PubMed - indexed for MEDLINE]

537: Vaccine. 2003 Jan 30;21(7-8):696-7.

Vaccination strategies against hepatitis A in southern Europe.

Franco E, Vitiello G.

Department of Public Health, University of Rome Tor Vergata, Via Montpellier 1,
00133, Rome, Italy. franco@med.uniroma2.it

Hepatitis A virus (HAV) infection is decreasing in southern European countries,
where epidemiological conditions vary among regions depending on the social and
health-care system development. In high endemic settings, HAV infection has not
heavy social and economic weight while in countries with a moderate/low degree of
endemia there is a call for targeted vaccination policy. In countries, like Spain
and in Italy, where several studies confirm an increase in susceptible adults,
vaccination strategies have been applied and recommendations have been published 
about hepatitis A prevention. Universal hepatitis A immunization seems
economically unattractive and most evidences for targeted vaccination have not
yet been sufficiently investigated. Vaccine should be used to protect travellers 
to countries where HAV infection is a major risk and in preventing secondary
cases and outbreaks.

PMID: 12531342 [PubMed - indexed for MEDLINE]

538: Arch Environ Health. 2002 Jul-Aug;57(4):332-6.

Risk of exposure to hepatitis A virus among day-care workers in Israel:
implications for preventive measures.

Peled T, Ashkenazi S, Chodick G, Aloni H, Yuhas Y, Lerman Y.

Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

Hepatitis A is an important infectious disease in Israel. The high incidence of
hepatitis A, the declining prevalence of antibodies against hepatitis A virus
throughout the past decade, and the availability of an active immunization for
hepatitis A have engendered the identification of occupations in which workers
are at increased risk of acquiring the disease. A prevalence study for hepatitis 
A antibodies was conducted during the first half of 1998 in a random sample of 37
day-care centers in different parts of Israel. A short interview was conducted,
and serum samples were then collected from each worker. The control group
comprised a sample of factory workers, blood donors, and women in maternity
wards. Ninety percent (402 of 446) of the day-care workers had antibodies to
hepatitis A. In a logistic-regression analysis, seropositivity was associated
with increased age, minimal education, and lack of military service. When the
authors compared a subsample of workers aged 18-40 yr with the control group,
seropositivity was associated with the following: birth in Israel, duration of
residence in Israel, very minimal education, military service, and employment in 
a day-care center. These results, together with earlier reports, indicate that
day-care workers are at high risk of occupational exposure to hepatitis A. These 
results may imply that seronegative workers have a 2-fold chance of acquiring
hepatitis A. Appropriate preventive measures should be considered, and active
immunization of susceptible workers should be undertaken.

PMID: 12530600 [PubMed - indexed for MEDLINE]

539: Intern Med. 2002 Dec;41(12):1188-92.

Hepatitis A virus infection associated with hemophagocytic syndrome: report of
two cases.

Watanabe M, Shibuya A, Okuno J, Maeda T, Tamama S, Saigenji K.

Department of Gastroenterology, Kitasato University East Hospital, Sagamihara,
Kanagawa.

Virus-associated hemophagocytic syndrome (VAHS) is reported to be a rare
complication in hepatitis A virus infections. We encountered two patients with
hepatitis A virus-associated hemophagocytic syndrome (HAV-AHS). Although
hemophagocytosis associated with other types of virus infections is fatal, the
present patients with HAV-AHS recovered well without any treatment.
Thrombocytopenia is an initial important finding of VAHS which is not rare in
patients with acute hepatitis A. If bone marrow aspiration is performed more
frequently, more HAV-AHS will be diagnosed. Further investigations are necessary 
to clarify the clinical features of HAV-AHS in more patients.

Publication Types: 
    Case Reports
    Review

PMID: 12521213 [PubMed - indexed for MEDLINE]

540: Tex Med. 2002 Dec;98(12):50-5.

A study of hepatitis A seropositivity in Dallas County, Texas, 1998 through 1999.

Fulda KG, Licciardone JC, Rene A, Blakley S.

Division of Education and Research, Department of Family Medicine, Texas College 
of Osteopathic Medicine, USA. kfulda@hsc.unt.edu

This paper provides background information on the epidemiology and a descriptive 
analysis of infection with hepatitis A virus in Dallas County, Texas, for 1998
and 1999. Reported cases were obtained from the Dallas County Health Department, 
and incidence rates per 100,000 population were calculated. Persons who tested
seropositive for hepatitis A virus between January 1, 1998, and December 31,
1999, were included. Variables of interest included age, sex, race, and date of
occurrence. The overall incidence rate of this infection in Dallas County for
1998 was 1.9 times higher than that of the United States; in 1999, the overall
rate for Dallas County increased by more than 1.6 times. Rates were significantly
higher among males, highest among Hispanics, and lowest among blacks for both
years. Incidence rates among age groups varied between years by increasing in
people 50 years and older from 1998 to 1999 as a result of a single
cafeteria-related outbreak of 150 cases in March 1999. Infection with hepatitis A
virus remains the most reported vaccine-preventable disease in the United States.

PMID: 12515248 [PubMed - indexed for MEDLINE]

541: Am J Phys Med Rehabil. 2003 Jan;82(1):28-32.

Comment in:
    Am J Phys Med Rehabil. 2003 Jul;82(7):563; author reply 563-4.

Serologic examinations of hepatitis, cytomegalovirus, and rubella in patients
with Bell's palsy.

Unlu Z, Aslan A, Ozbakkaloglu B, Tunger O, Surucuoglu S.

Department of Physical Medicine and Rehabilitation, Celal Bayal University,
Manisa, Turkey.

OBJECTIVE: The aim of this retrospective case review was to investigate serologic
evidence of cytomegalovirus, rubella virus, and hepatitis A, B, and C viruses in 
patients with Bell's palsy. DESIGN: A total of 24 patients with idiopathic facial
paralysis, without a history of trauma, any evidence of a tumor on
high-resolution computed tomographic imaging, or any otologic disease, and 33
healthy individuals as a control group were included in this study. Facial
paralysis of the patient was evaluated with the House-Brackmann grading scale.
Specific immunoglobulin G and M titers were determined for cytomegalovirus,
rubella, hepatitis A, hepatitis B, and hepatitis C by enzyme-linked immunosorbent
assay. RESULTS: Serologic positivity for hepatitis B was found in 15 of 21 Bell's
palsy patients, compared with 32.1% in the control group. The difference was
statistically significant. There was no difference in the prevalence of serologic
positivity for cytomegalovirus, hepatitis A, and rubella between the patient and 
control groups. In one Bell's palsy patient, serologic evidence of recent
cytomegalovirus infection was indicated by changes in antibody titers between
samples taken on presentation and on the 16th day. There was no serologic
evidence of hepatitis C in either Bell's palsy patients or the control group.
CONCLUSION: There seems to be an association between hepatitis B and idiopathic
facial paralysis. In addition, cytomegalovirus might contribute to the
development of Bell's palsy in some ceases with Bell's palsy. Further studies are
required to confirm these data.

PMID: 12510182 [PubMed - indexed for MEDLINE]

542: J Virol Methods. 2003 Feb;107(2):223-8.

Mixed infection of a child care provider with hepatitis A virus isolates from
subgenotypes IA and IB revealed by heteroduplex mobility assay.

de Paula VS, Saback FL, Gaspar AM, Niel C.

Department of Virology, Oswaldo Cruz Institute, Av. Brasil 4365, 21045-900, RJ,
Rio de Janeiro, Brazil.

Phylogenetic analysis based on a 168 base segment encompassing the putative
VP1/2A junction of the hepatitis A virus (HAV) genome has enabled the
classification of HAV isolates into seven genotypes (I-VII). Genotype I, which
includes the vast majority of the human HAV isolates, has been divided further
into subgenotypes IA and IB. An heteroduplex mobility assay was designed with
amplification products from the VP1/2A junction region, and used as a genotyping 
method able to discriminate HAV isolates belonging to IA, IB and non-I genotypes.
The method was used to successfully genotype 48 samples (16 IA and 32 IB).
However, one HAV RNA positive serum sample (AUX-23), collected from a 15 year old
female employed at a child care center located in Rio de Janeiro, Brazil, showed 
an unusual pattern. PCR products from sample AUX-23 gave rise to heteroduplex
bands when mixed with IA products as well as with IB products, suggesting the
presence of HAV isolates from both subgenotypes in the serum. PCR products from
sample AUX-23 were then cloned and 20 clones were analyzed by heteroduplex
mobility assay. Eleven were subgenotype IA and 9 were IB. Three clones of each
subgenotype were then sequenced to confirm the results. These data constitute the
first report of mixed infection of a single individual with different HAV
isolates.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12505637 [PubMed - indexed for MEDLINE]

543: Hepatology. 2003 Jan;37(1):44-51.

Cost-effectiveness of hepatitis A vaccination in children, adolescents, and
adults.

Rosenthal P.

Pediatric Liver Transplant Program, University of California, San Francisco,
94143, USA. prosenth@peds.ucsf.edu

Hepatitis A is a major public health problem in the United States and other
developed countries, largely because decreased natural immunity allows for
increased susceptibility. To evaluate the cost-effectiveness of routine
vaccination of children, adolescents, and certain high-risk adults against
hepatitis A, economic analyses of hepatitis A vaccination were identified through
searches of MEDLINE, EMBASE, and BIOSIS (February, 1992, to December, 2001) for
studies, reviews, editorials, and letters from peer-reviewed journals published
in English, French, German, Italian, or Spanish. Experts were also contacted.
Articles conforming to accepted standards of quality for health-economic studies 
were used to compile data on vaccination of children, and results were
synthesized in a narrative review. This review of economic analyses of vaccine
use in several developed countries shows cost-effectiveness comparable with that 
of other vaccines in children and within accepted boundaries for adolescents and 
high-risk adults.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.
    Review

PMID: 12500187 [PubMed - indexed for MEDLINE]

544: Braz J Infect Dis. 2002 Oct;6(5):225-31.

Seroprevalence of hepatitis a antibodies in a group of normal and Down syndrome
children in Porto Alegre, southern Brazil.

Ferreira CT, Leite JC, Tanaguchi AN, Vieira SM, Pereira-Lima J, da Silveira TR.

Graduate Program in Gastroenterology, Clinical Hospital of Porto Alegre, Federal 
University of Rio Grande do Sul, Porto Alegre, Brazil. cristina@qbnet.com.br

The high incidence of Hepatitis A and B in institutionalized patients with Down
Syndrome (DS) is not fully understood. Under poor hygienic conditions,
immunological alterations might predispose individuals to these infections. Sixty
three DS children between 1 and 12 years old living at home with their families
were examined for anti-HAV and compared to age-matched controls (64 healthy
children). This cross-sectional study was carried out from May 1999 to April 2000
at the Hospital de Clínicas of Porto Alegre, southern Brazil. Groups were
compared in terms of age, sex, skin color, and family income (> R$ 500 and < R $ 
500/month) by the chi-square test, with Yates' correction and for the prevalence 
of anti-HAV (Fisher's exact test). In the DS group (n=63), the mean age was 4.4
+/- 3.3 years, 94% of the patients were white and 51% were female. Family income 
was < or = R$ 500/month in 40 cases (63%). In the control group (n=64), the mean 
age was 4.8 +/- 2.7 years, 81% of the patients were white and 56% were female.
Family income was < or = R$ 500 in 20 patients (31%). DS children's families had 
a significantly lower income (P<0.0005). In the DS group there were 6 positive
(9.5%) anti-HAV cases, and all came from low-income families (less than R$ 500/
month). In the control group, 3 cases (4.7%) were positive for anti-HAV (two were
from a low-income family and one was from a higher income family). These
differences were not significant. Our data indicate that Hepatitis A is not a
special risk for mentally retarded DS outpatients, even in a developing country
like Brazil.

PMID: 12495604 [PubMed - indexed for MEDLINE]

545: Infection. 2002 Dec;30(6):334-7.

Hepatitis agents with enteric transmission--an epidemiological analysis.

Yayli G, Kiliç S, Ormeci AR.

Dept. of Clinical Microbiology and Infectious Diseases, S. Demirel University,
Faculty of Medicine, Isparta, Turkey.

BACKGROUND: Viral hepatitis is characterized by special clinical, biochemical and
serological findings. This study was planned to determine the seroprevalence,
epidemiological characteristics and clinical and biochemical findings of
hepatitis A virus (HAV) and hepatitis E virus (HEV) infections during an outbreak
of jaundice. MATERIALS AND METHODS: 340 children aged 5-16 years were included.
Clinical findings and alanine aminotransferase (ALT) levels were documented.
Anti-HAV IgG and IgM in addition to anti-HEV IgG and IgM were determined by
microELISA. RESULTS: Clinical findings, high levels of ALT, anti-HAV IgM and IgG,
anti-HEV IgM and IgG were present in 6%, 23%, 17%, 100%, 7% and 9% of cases,
respectively. The relationship between ALT levels and anti-HAV or anti-HEV IgM
seropositivity was significant (p </= 0.0001). CONCLUSION: HAV and HEV infection 
were both caused by a contaminated water supply.

PMID: 12478320 [PubMed - indexed for MEDLINE]

546: J Infus Nurs. 2002 Nov-Dec;25(6):379-82.

Current treatments for hepatitis.

Fleming J.

jean_fleming@att.net

Common viral agents known to cause inflammation of the liver (hepatitis) are
hepatitis A virus (HAV), hepatitis B virus (HBV), and hepatitis C virus (HCV).
Some other viral agents that can cause hepatitis are Epstein Barr virus, herpes
simplex virus, and cytomegalovirus. Some patients infected with these viral
agents progress to develop chronic viral hepatitis. Approximately 45% of chronic 
hepatitis cases are associated with hepatitis C and approximately 15% are
associated with hepatitis B. In addition to being a leading cause of chronic
hepatitis, HCV is most frequently associated with liver cirrhosis and
hepatocellular carcinoma. Although much has been published about HAV and HBV,
health professionals have learned about HCV only in recent years. For this
reason, this article will emphasize the epidemiologic challenges and current
treatments for hepatitis C; hepatitis A and B will be discussed in brief.

PMID: 12464795 [PubMed - indexed for MEDLINE]

547: J Gastroenterol Hepatol. 2002 Nov;17(11):1187-91.

Comparison of clinical manifestations and epidemiology between acute hepatitis A 
and acute hepatitis E in Taiwan.

Su CW, Wu JC, Huang YS, Huo TI, Huang YH, Lin CC, Chang FY, Lee SD.

Division of Gastroenterology, Department of Medicine, Taipei Veterans General
Hospital, Taiwan.

BACKGROUND AND AIMS: Acute hepatitis A (AHA) and acute hepatitis E (AHE) are
endemic in developing countries. They share similar transmission routes and
clinical manifestations. To compare the differences in epidemiology, clinical
picture and prognosis between these two enterically transmitted forms of
hepatitis, we enrolled 58 consecutive AHA or AHE patients (42 men and 16 women;
age 16-74 years) from January 1990 to April 2001. RESULTS: In comparison to AHA, 
patients with AHE were older (56.2 +/- 15.4 vs 30.7 +/- 11.0 years, P < 0.0001), 
and more frequently had a history of travel within 3 months before onset of
illness (68.8 vs 30.8%, P = 0.003). In laboratory data, AHE patients had lower
serum levels of albumin (3.4 +/- 0.4 vs 3.8 +/- 0.4 g/dL, P = 0.016), alanine
aminotransferase (1912 +/- 1587 vs 3023 +/- 1959 U/L, P = 0.015), and aspartate
aminotransferase (1681 +/- 1444 vs 2374 +/- 2869 U/L, P = 0.24), but a higher
serum bilirubin level (17.8 +/- 12.3 vs 8.7 +/- 5.0 mg/dL, P = 0.003) than AHA
patients. Moreover, five (15.6%) patients with AHE compared with none with AHA
died. This probably indicates that AHE had a worse outcome than AHA in our study.
In analysis of epidemiological factors, older age of onset of illness was the
only significant predicator of outcome. From an epidemiological survey, most AHE 
patients were imported while most AHA patients were not. However, native AHE and 
imported AHA did occur in Taiwan. CONCLUSION: Patients with AHE in Taiwan had
older age of onset, more records of traveling history, and poorer clinical
manifestations than those with AHA, and age seemed to be the most important
factor to influence outcome. Copyright 2002 Blackwell Publishing Asia Pty Ltd

Publication Types: 
    Comparative Study

PMID: 12453278 [PubMed - indexed for MEDLINE]

548: Can J Public Health. 2002 Nov-Dec;93(6):435-8.

Hepatitis A, B, and C in Canada. Results from the National Sentinel Health Unit
Surveillance System, 1993-1995.

elSaadany S, Gully P, Giulivi A.

Statistics and Risk Assessment Section, Health Care Acquired Infections Division,
Population and Public Health Branch, Health Canada, A.L. 0601E2, Building No. 6, 
Tunney's Pasture, Ottawa, ON K1A 0L2. Susie_ElSaadany@hc-sc.gc.ca

OBJECTIVES: To estimate the incidence of and to describe the risk factors that
were associated with the acquisition of hepatitis A, B, and C in well-defined
Canadian populations from the Sentinel Health Unit Surveillance System (SHUSS).
METHODS: We used the 1993 to 1995 data on hepatitis A, B, and C infection in
Canada, collected by SHUSS, a national surveillance system established by the
Laboratory Centre for Disease Control in Health Canada in 1993, through
consultation and collaboration with provincial partners. We calculated the rates 
of, and described and discussed the risk factors that were associated with,
hepatitis A, B, and C infection, based on the SHUSS surveillance data. RESULTS:
From 1993 to 1995, SHUSS reported 92 cases of hepatitis A, 89 hepatitis B, and
720 hepatitis C, yielding a rate of 3.9, 3.8, and 30.3 per 100,000, respectively.
The reported rates varied substantially among participating health units, ranging
from 0.8 to 8.1 per 100,000 for hepatitis A, 0.0 to 9.0 for hepatitis B, and 5.4 
to 73.3 for hepatitis C. The most frequently reported risk factor for hepatitis A
was a history of street drug use, followed by recent international travel and
household contact with a hepatitis A case, household crowding, and a history of
raw or undercooked shellfish consumption. The most frequently reported risk
factors for the acquisition of hepatitis B included history of street drug use
and occupational exposure. The most frequently reported risk factor for the
acquisition of hepatitis C was a history of street drug use, followed by health
care exposure and occupational exposure. Only 5% of persons with hepatitis B
infection had a history of hepatitis B immunization. INTERPRETATION: Despite the 
limitations of possible bias due to selective participation of SHUSS and the lack
of information on risk factors among controls, the high exposure to known risk
factors and the low rate of vaccination among hepatitis patients can provide
useful information for the development of public health policies to control
hepatitis A, B, and C infection in Canada.

PMID: 12448866 [PubMed - indexed for MEDLINE]

549: Mil Med. 2002 Nov;167(11):907-10.

The utility of prescreening for hepatitis A in military recruits prior to
vaccination.

Hirota WK, Duncan MB, Hirota WK, Tsuchida A.

Madigan Army Medical Center, Department of Medicine, Fort Lewis, Tacoma, WA
98431-5009, USA.

The U.S. Army administers the hepatitis A virus (HAV) vaccination for prophylaxis
against HAV infection. There is little comparative data as to whether
prescreening for previous HAV infection before immunization is less costly than
universal vaccination. We designed a study to determine the prevalence of
previous HAV infection in U.S. Army recruits and then perform a cost analysis.
The cost analysis compared selective vaccination versus universal vaccination.
Basic demographic information, including age, gender, geographic origin, and
ethnicity, were collected after which patients were tested for HAV antibodies. A 
total of 1,332 individuals was prospectively enrolled with 183 individuals
(13.74%) having evidence of previous HAV infection. Minority recruits were found 
to have a higher prevalence than Caucasian recruits (p = 0.0451. The cost
analysis demonstrates that vaccination without prescreening was the least costly 
of two vaccination strategies for this cohort. To achieve current vaccination
goals, all U.S. military recruits should be vaccinated without evaluation for
previous HAV immunity.

PMID: 12448616 [PubMed - indexed for MEDLINE]

550: Med Sci Monit. 2002 Nov;8(11):CR762-6.

Prevalence of markers of hepatotropic viruses A, B, C and the efficacy of
vaccination against hepatitis A and hepatitis B among medical students.

Jabłkowski M, Kuydowicz J, Strzelczyk J, Białkowska J.

Clinic for Infectious Diseases, Medical University, Ł dź, Poland.
m.jablkowski@pro.onet.pl

BACKGROUND: Hepatitis A and B can be prevented by active immunization. The
purpose of our study was to estimate the prevalence of viral markers of hepatitis
A, B, and C among medical students, to assess the efficacy of vaccination against
HBV infection after 4 years, and to evaluate the efficacy of vaccination against 
HAV infection. MATERIAL/METHODS: The study group consisted of 150 medical
students, who were vaccinated with Engerix B at the beginning of medical studies.
From this population we identified a subgroup of 45 students, in whom the
presence of anti-HAV was not confirmed; they were then vaccinated with HAVRIX
1440. Viral markers for HAV, HBV, HCV were determined in this group. RESULTS: In 
the group of 150 persons, we found anti-HBc in 8 students (5.3%), and HBsAg in 1 
(0.7%), who did not have either HBeAg or anti-HBe. Anti-HBs antibodies were found
in 146 students (97.3%); anti-HCV in 3 cases (2%), and anti-HAV in 15 cases
(10%). After 2-fold vaccination against viral hepatitis A, 100% of the students
presented with anti-HAV. CONCLUSIONS: The incidence of HBsAg and anti-HCV among
our students is the same as in the general population, while the incidence of
anti-HAV is much lower (10%). The presence of anti-HBs 4 years after vaccination 
was detected in 97.3% of the students, and anti-HAV 1 month after the complete
course of vaccination in 100% of cases.

PMID: 12444381 [PubMed - indexed for MEDLINE]

551: Clin Infect Dis. 2002 Dec 1;35(11):1382-7. Epub 2002 Nov 13.

Preventing hepatitis A and hepatitis B virus infections among men who have sex
with men.

Kahn J.

Department of Medicine, Positive Health Program, University of California, San
Francisco, and San Francisco General Hospital, San Francisco, CA 94110, USA.
jkahn@php.ucsf.edu

Hepatitis A and hepatitis B are 2 common sexually transmitted diseases that are
preventable by vaccination. Men who have sex with men (MSM) are at increased risk
of acquiring hepatitis A virus and hepatitis B virus through sexual exposure.
Current guidelines from the Centers for Disease Control and Prevention recommend 
that MSM receive immunizations against hepatitis A and hepatitis B. Many health
care providers and most MSM are unaware of the risks and the potentially
dangerous consequences posed by hepatitis A and B virus infection, and the MSM
thus remain unvaccinated and unprotected from exposure to these viruses. It is
important for health care providers to educate and vaccinate their at-risk male
patients against hepatitis A and hepatitis B virus infections.

PMID: 12439802 [PubMed - indexed for MEDLINE]

552: Rev Inst Med Trop Sao Paulo. 2002 Sep-Oct;44(5):289-92.

Seasonal variation of hepatitis A virus infection in the city of Rio de Janeiro, 
Brazil.

Villar LM, De Paula VS, Gaspar AM.

Departament of Virology, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro,
21045-900, Brasil. lvillar@ioc.fiocruz.br

Hepatitis A virus (HAV) infection constitutes a major public health problem in
Brazil. The transmission of HAV is primarily by fecal-oral route so the water is 
an important vehicle of HAV dissemination. There is a great incidence of acute
cases of hepatitis A in some areas of Brazil however the seasonal variation of
these cases was not documented. The aim of this study was to determine the
seasonality of HAV infection in Rio de Janeiro. From January 1999 to December
2001, 1731 blood samples were collected at the National Reference Center for
Hepatitis Viruses in Brazil (NRCHV). These samples were tested by a commercial
enzyme-immunoassay to detect anti-HAV IgM antibodies. Yearly positive rates were 
33.74% in 1999, 32.19% in 2000, and 30.63% in 2001. A seasonal variation was
recognized with the highest incidence in spring and summer. Furthermore a
seasonal increase in incidence of HAV infection was found during the rainy season
(December to March) because the index of rains is very high. It is concluded that
HAV infections occur all year round with a peak during hot seasons with great
number of rains.

PMID: 12436171 [PubMed - indexed for MEDLINE]

553: J Viral Hepat. 2002 Nov;9(6):460-5.

Risk of hepatitis A infection following travel.

Ciccozzi M, Tosti ME, Gallo G, Ragni P, Zotti C, Lopalco P, Ara G, Sangalli M,
Balocchini E, Szklo AS, Mele A; SEIEVA collaborating group.

Laboratorio di Epidemiologia e Biostatistica, Istituto Superiore di Sanità, Roma,
Italia.

Travel to endemic areas is one of the most frequently reported risk factors for
infection with the hepatitis A virus (HAV). We evaluated the association between 
HAV infection and travel, by area of destination. We conducted a case-control
study on all cases of HAV infection reported to the Italian National Surveillance
System for Acute Viral Hepatitis in the period 1996-2000. The study population
consisted of 9695 persons with HAV infection (cases) and 2590 with HBV infection 
(controls). The risk of acquiring HAV was highest for travel to Asia, Africa and 
Latin America [Odds Ratio = 9.30 (95%CI = 6.71-12.9)]; a three-fold statistically
significant excess of risk was found for travel to southern Italy (OR = 3.03) and
to the Mediterranean Area and Eastern Europe (OR = 3.15). Travel was implicated
in 28% of the cases of HAV infection. When stratifying the analysis by area of
residence (northern and central Italy vs southern Italy and the Islands), the
above-mentioned risks were confirmed only for those residing in northern and
central Italy, with no significant risk for those residing in southern Italy and 
the Islands. Travel to areas endemic for HAV infection constitutes a considerable
risk. Our results highlight the importance of developing health policies for
improving environmental and hygienic conditions, as well as the prevention of
certain eating habits. Vaccination before travelling to a medium or high endemic 
area could be a safe and effective means of preventing travel-related HAV
infection.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12431210 [PubMed - indexed for MEDLINE]

554: Indian Pediatr. 2002 Oct;39(10):936-41.

Prevalence of hepatitis A in children and adolescents in Adana, Turkey.

Yapicioglu H, Alhan E, Yildizdas D, Yaman A, Bozdemir N.

Department of Pediatrics, Cukurova University, Faculty of Medicine, Adana,
Turkey.

The present study was aimed at determining the seroprevalence of anti-HAV in
children and adolescents in the city of Adana, Turkey. The overall prevalence of 
anti-HAV was 44.4% (316/711). The prevalence increased with advancing age i.e.
28.8% (2.1-6 yr), 49.8% (6.1-12 yr), and 68% (12.1-16.5 yr) (P < 0.0001).
Seroprevalence was significantly lower in children less than 6 years and
belonging to higher socioeconomic status.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12428039 [PubMed - indexed for MEDLINE]

555: Indian J Med Res. 2002 Jan;115:1-4.

Serological study of hepatitis A virus infection amongst the students of a
medical college in Delhi & evaluation of the need of vaccination.

Jindal M, Rana SS, Gupta RK, Das K, Kar P.

Department of Medicine, Gastroenterology Division, Maulana Azad Medical College, 
New Delhi, India.

BACKGROUND & OBJECTIVES: Recent seroepidemiological studies have demonstrated a
decrease in the seroprevalence of hepatitis A virus (HAV) infection, thereby
increasing the pool of susceptible adult population. Health care workers,
especially those working in paediatric wards and nurseries, are at an increased
risk of developing HAV infection. The present study was undertaken to determine
the prevalence of antibody against HAV (IgG anti-HAV) among a batch of medical
students of the Maulana Azad Medical College, New Delhi, so as to identify the
proportion of students who would be susceptible to HAV infection and hence would 
benefit from a vaccination programme against HAV. METHODS: A total of 91 medical 
students were enrolled and divided into groups on the basis of sex. The serum
samples were evaluated for the presence of immunoglobulin (IgG) against HAV (IgG 
anti-HAV) using a commercially available enzyme linked immunosorbent assay
(ELISA) kit. RESULTS: The mean age of all the subjects was 19.9 +/- 1.5 yr and
the male: female ratio was 1.2: 1. Fifty seven (62.6 +/- 5.1%) students were
positive for IgG anti-HAV while 34 (37.4%) were seronegative and hence
susceptible to HAV infection. No statistically significant difference was
observed in the seroprevalence of HAV between males and females [64 +/- 6.7%
(32/50) versus 60.9 +/- 7.6% (25/41)]. INTERPRETATION & CONCLUSION: our results
indicate that more than one-third of the medical students were seronegative for
IgG anti-HAV and hence at an increased risk of developing HAV infection as a
result of occupational exposure. Therefore, we suggest that students in a health 
care set up should undergo vaccination against HAV after pre-vaccination immunity
screening.

PMID: 12424929 [PubMed - indexed for MEDLINE]

556: J Clin Microbiol. 2002 Nov;40(11):4148-55.

Molecular characterization of hepatitis a virus isolates from a transcontinental 
shellfish-borne outbreak.

Sánchez G, Pintó RM, Vanaclocha H, Bosch A.

Department of Microbiology, University of Barcelona, Barcelona. Department of
Epidemiology, Generalitat Valenciana, Valencia, Spain.

One hundred eighty-four serologically confirmed cases of hepatitis A were
reported in eastern Spain in 1999. A matched case-control study implicated
imported coquina clams complying with European Union shellfish standards as the
source of infection; this implication was confirmed by the detection by reverse
transcription-PCR of hepatitis A virus (HAV) RNA in shellfish samples. In spite
of the recognized low variability of HAV, genetic characterization of the
complete capsid region of virus isolates from patient serum samples revealed the 
existence of both synonymous and nonsynonymous variants. Two antigenic variants
were detected, one in a discontinuous epitope defined by monoclonal antibody
K3-4C8 and a second in a linear VP1 epitope of the virus. In spite of these
antigenic variants, all isolates were assigned to genotype IB, providing further 
evidence that the outbreak originated from a common source, although multiple
strains were likely to be involved.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12409389 [PubMed - indexed for MEDLINE]

557: Turk J Pediatr. 2002 Jul-Sep;44(3):204-10.

Hepatitis A seroprevalence in a random sample of the Turkish population by
simultaneous EPI cluster and comparison with surveys in Turkey.

Kanra G, Tezcan S, Badur S; Turkish National Study Team.

Department of Pediatrics, Hacettepe University, Faculty of Medicine, Ankara,
Turkey.

This study was conducted to determine the hepatitis A virus (HAV) seroprevalence 
in nine provinces representative of Turkey as a whole. These provinces are
representative of the country's geographical location, and demographic, economic 
and social characteristics. In each province, sample sizes were determined using 
published data on HAV seroprevalence, and sample sizes for each province and for 
the cluster were calculated for each group of subjects under the age of 30 for
seroprevalence estimates within a 95% confidence interval. The samples were
selected by a cluster method, and the planned recruitment was a total of 4,800
subjects, including 600 subjects each from five large provinces (Istanbul,
Ankara, Izmir, Adana, Diyarbakir) and 450 subjects from each of the remaining
four provinces (Samsun, Erzurum, Trabzon, Edirne). These numbers were distributed
in accordance with the percentages for age groups in five-year increments
starting from age five for the population under the age of 30 living in the rural
and urban areas in each province. This study of 4,462 subjects under the age of
30 in nine provinces of Turkey identified an overall HAV seroprevalence rate of
71.3%. The distribution of HAV seroprevalences by age showed a steady increase
from one year of age from 42.7% to 91.1% at 25-29 years of age. HAV
seroprevalence was slightly higher in female subjects (73%) than in male subjects
(69.3%). By educational status, seroprevalences were comparable except in young
children under age six. Seroprevalence was notably higher in large families with 
six and more members (80.1%) than in small families with five or fewer members
(66.7%). According to our study results, 50% of Turkish children are seropositive
for HAV by the age of 10 years. We believe the date support the need for a
routine primary immunization policy in Turkey and the development of effective
prophylactic programs after possible exposure. Consequently, an immunization
policy can be developed for each region according to its epidemiological
conditions.

PMID: 12405430 [PubMed - indexed for MEDLINE]

558: Dig Liver Dis. 2002 Sep;34(9):656-9.

Anti-hepatitis A virus seroprevalence and seroconversion in a cohort of patients 
with chronic viral hepatitis.

Stroffolini T, Almasio PL, Di Stefano R, Andreone P, Di Gaetano G, Fattovich G,
Gaeta GB, Morisco F, Smedile A, Tripi S, Zignego AL, Ferraro D, Mele A, Craxi A.

Epidemiology Laboratory, Istituto Superiore di Sanità, Rome, S Giacomo Hospital, 
Italy.

BACKGROUND: Patients with chronic hepatitis C infected by hepatitis A virus have 
a substantial risk of fulminant hepatitis or death, while the course of hepatitis
A virus is uncomplicated in most subjects with chronic hepatitis B. AIM: To
evaluate the prevalence of anti-hepatitis A virus antibodies and the incidence of
hepatitis A virus seroconversion in a nationwide sample of 530 patients with
chronic hepatitis B and/or hepatitis C infection initially susceptible to this
infection after a follow-up of some years. RESULTS: The overall anti-hepatitis A 
virus prevalence was 85.7%, with no difference between males and females. By the 
age of 50 years, almost all patients were found to have been exposed to hepatitis
A virus. After a mean follow-up period of 76 months the overall anti-hepatitis A 
virus seroconversion rate in the 76 initially susceptible individuals was 1.2 per
100 person/years. However, it was 0.3 per 100 person/years in those hepatitis B
surface antigen positive but 3.36 per 100 person/years in those anti-hepatitis C 
virus positive. None of the seroconverters was affected by a clinically evident
disease or showed deterioration of underlying chronic liver disease. CONCLUSIONS:
The present study shows that Italian patients >50 years of age with chronic liver
disease have already been exposed to hepatitis A virus suggesting that
anti-hepatitis A virus screening is not advisable in these subjects.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12405253 [PubMed - indexed for MEDLINE]

559: World J Gastroenterol. 2002 Oct;8(5):872-8.

Mutational characteristics in consecutive passage of rapidly replicating variants
of hepatitis A virus strain H2 during cell culture adaptation.

Hu NZ, Hu YZ, Shi HJ, Liu GD, Qu S.

Department of Vaccine Research, Institute of Medical Biology, Chinese Academy of 
Medical Sciences, Peking Union of Medical College, Kunming, 650118, Yunnan
Province, China.

AIM: To investigate the molecular mechanism of cell adaptation and rapid
replication of hepatitis A virus strain H2 in KBM17 cells. METHODS: Virus of
strain H2 at passage 7 was consecutively passaged in KBM17 cells for 22 passages,
every passage was incubated for 14 days. Antigenic and infectious titers of every
passage and one-step growth dynamics of passage 22 were determined with ELISA.
Genomes of passage 6, passage 12, passage 18 and passage 22 were sequenced and
compared with H2K7. RESULTS: During continuous passage of vaccine strain H2 at
passage K7 in KMB17 cells, infectious and antigenic titers increased with the
increase of passages, infectious titers at day 14 reached 6.77LgCCID(50)ml(-1)
for passage 6 (P6), 7.0 LgCCID(50)ml(-1) for passage 12 (P12), 7.33
LgCCID(50)ml(-1) for passage 18 (P18) and 7.83 LgCCID(50)ml(-1) for passage 22
(P22), respectively. The one-step growth dynamics showed that replicating peak of
P22 appeared at day 14 with infectious titers of 7.83 LgCCID(50)ml(-1) and
antigenic titer of 1:1024. After passage 22 a new cell-adapted variant (P22) of
H2K7 with rapid and shortened replication cycle from 28 days to 14 days was
obtained. Sequencing and comparisons of genomes of P6, P12, P18 and P22 showed
that mutational numbers in genomes of different passages increased with adaptive 
passages, and mutations scattered over the genome. In comparison with that of K7,
P6 had only 6 nucleotides (nt) mutations, P12 had 7 mutational changes, in
addition to 6 same mutations with P6, there appeared a new mutation in 5'NTR at
nucleotide position 591 resulting in a nucleotide exchange from A to G. P18 had
10 nt mutations, among the 10 mutations, 7 mutational changes were same as with
P12, three new mutational changes appeared in the genome, one in 5'NTR, one in 3C
coding region, one in 3D coding region, at P22 there appeared 18 nucleotide
changes in the genome, on the basis of P18,there occurred additional 8 nucleotide
mutations, two in 5'NTR, three in 2C, one in 3A, one in 3C and one in 3D. The
results suggested that although H2K7 was already an attenuated strain, the
mutations of genome is not sufficient to completely adapt the KMB17, further
mutations caused rapid replication adaptation. CONCLUSION: 18-nt changes
scattering over the genome are cooperatively responsible for further adaptation
characterized by rapid and shortened replication cycle from 28 days to 14 days in
KMB17 cells. The mutations in 2C coding region play more important role in
increase of infectious titer than other mutations, the mutations in 2B coding
region show less important role than it usually does in cell adaptation,
nucleotide changes in 5' NTR seem to be not relevant to cell adaptation during
initial stages (before P6), but do in late stages.

PMID: 12378633 [PubMed - indexed for MEDLINE]

560: Bull World Health Organ. 2002;80(9):728-31.

Vaccination against hepatitis A virus may not be required for schoolchildren in
northern India: results of a seroepidemiological survey.

Batra Y, Bhatkal B, Ojha B, Kaur K, Saraya A, Panda SK, Acharya SK.

Department of Gastroenterology, All India Institute of Medical Sciences, New
Delhi, India.

OBJECTIVES: To evaluate the current seroprevalence of antibodies against
hepatitis A virus (HAV) in a sample of schoolchildren above 10 years of age and
to determine the prevalence of HAV-induced hepatitis in adults at a tertiary care
hospital in northern India between January 1992 and December 2000. METHODS: Sera 
from 276 male and 224 female schoolchildren aged 10-17 years were tested for
anti-HAV antibodies by enzyme-linked immunosorbent assay. Consecutive patients
with a diagnosis of acute viral hepatitis who attended a liver clinic were tested
for the serological markers of HAV, hepatitis B Virus, hepatitis C virus,
hepatitis D virus, and hepatitis E virus. FINDINGS: Of the male and female
children, 96.3% and 98.2%, respectively had anti-HAV antibodies in their sera.
The prevalence of these antibodies in the age groups 10-12, 13- 14, and 15-17
years were 98.6%, 94.8%, and 98.3% respectively. The frequency of HAV- induced
acute viral hepatitis (69/870, 8%) in adults did not show an increasing trend.
CONCLUSION: Mass HAV vaccination may be unnecessary in northern India because the
seroprevalence of protective antibodies against HAV in schoolchildren aged over
10 years remains above 95% and there has been no apparent increase in HAV-induced
acute viral hepatitis in adults.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12378291 [PubMed - indexed for MEDLINE]

561: N Z Med J. 2002 Jul 26;115(1158):U106.

Sexually transmitted diseases and hepatitis in a national sample of men who have 
sex with men in New Zealand.

Saxton PJ, Hughes AJ, Robinson EM.

New Zealand AIDS Foundation, Auckland, New Zealand. research@nzaf.org.nz

AIMS: To investigate the lifetime self-reported incidence of sexually transmitted
diseases and hepatitis A, B and C in a national sample of men who have sex with
men (MSM) in New Zealand. METHODS: A national telephone survey of MSM was
conducted in 1996 with the aim of collecting baseline information on the sexual
behaviour, safe sex practices, socio-sexual milieu and HIV knowledge of a broad
range of MSM. RESULTS: Of the 1852 respondents, 37.1% reported a lifetime history
of sexually transmitted diseases (STDs), 7.0% reported hepatitis A, 8.0%
hepatitis B and 1.8% hepatitis C. A quarter (26.2%) had been for a sexual health 
check-up or treatment in the year prior to survey. Logistic regression analysis
revealed independent associations with STD history (older age, higher number of
lifetime partners, seeking partners in public venues, tested HIV positive), HAV
(older age, higher number of lifetime partners, use of sex venues, tested HIV
positive), HBV (older age, seeking partners in public venues, tested HIV
positive), HCV (lower income, recent injecting drug use, tested HIV positive).
CONCLUSIONS: This is the first time that information on STDs and hepatitis among 
a large national sample of MSM has been collected in New Zealand. The findings
corroborate previous evidence that MSM are disproportionately affected by
sexually transmitted infections other than HIV.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12362181 [PubMed - indexed for MEDLINE]

562: J Infect Dis. 2002 Oct 15;186(8):1081-5. Epub 2002 Sep 20.

Impact of recurrent epidemics of hepatitis a virus infection on population
immunity levels: Bristol Bay, Alaska.

Peach D, McMahon BJ, Bulkow L, Funk E, Harpaz R, Margolis HS.

Arctic Investigations Program, National Center for Infectious Diseases, Centers
for Disease Control and Prevention, 4055 Tudor Centre Drive, Anchorage, AK 99508,
USA.

The dynamics of population-based immunity were examined by using serologic
surveys of 7 villages in rural Alaska between 2 epidemics of hepatitis A virus
(HAV) and after the second epidemic (1988-1990). Among persons aged 2-30 years,
the overall age-adjusted prevalence of antibody to HAV (anti-HAV) was 51% in 1983
and 49% in 1993 (P=.506). In children aged <5 years, prevalence rates were 0% and
11% in 1983 and 1993, respectively. The prevalence of HAV infection increased
with age in both surveys. When examined by 5-year birth cohorts, anti-HAV
prevalence increased in children born between 1979 and 1983 (P<.001). Between the
2 survey periods, 43 clinical cases of HAV infection were reported in these
villages; all occurred from 1988 to 1990. Despite high overall prevalence of
immunity, transmission during epidemics was facilitated by children aged <15
years susceptible to HAV. Little transmission occurred between epidemics.
Vaccination of children against HAV should prevent future epidemics.

Publication Types: 
    Research Support, U.S. Gov't, P.H.S.

PMID: 12355357 [PubMed - indexed for MEDLINE]

563: Nephrol Dial Transplant. 2002 Oct;17(10):1825-8.

Active immunization against hepatitis A in dialysis patients.

Fleischmann EH, Kruppenbacher J, Bock HL, Weber M.

Medizinische Klinik IV der Universität Erlangen Nürnberg, Virologisches Institut 
der Universität zu Köln, Germany.

BACKGROUND: This study investigated the feasibility, immunogenicity, and
reactogenicity of hepatitis A vaccination in end-stage renal failure patients who
were on chronic intermittent haemodialysis. METHODS: Forty-three subjects were
vaccinated with an inactivated hepatitis A vaccine according to a 0-, 1-, and
6-month immunization schedule. Two groups were established who received the
vaccine either intramuscularly (group A, n=30) or subcutaneously (group B, n=13).
RESULTS: All patients in group A and 12/13 in group B developed antibodies
against hepatitis A. The geometric mean titres (GMT) were high and similar to
those observed in healthy subjects. There was a tendency to higher GMT in the
group who received the vaccine subcutaneously. No clinically significant adverse 
events were observed, and the liver enzyme profile showed no abnormalities.
CONCLUSIONS: We showed that hepatitis A vaccination of dialysis patients is
feasible, well tolerated and immunogenic and that the vaccine can be given
subcutaneously in those patients where intramuscular administration is
contra-indicated.

PMID: 12270992 [PubMed - indexed for MEDLINE]

564: Sex Transm Infect. 2002 Jun;78(3):174-9.

Seroprevalence of hepatitis A immunity in male genitourinary medicine clinic
attenders: a case control study of heterosexual and homosexual men.

Ross JD, Ghanem M, Tariq A, Gilleran G, Winter AJ.

Whittal Street Clinic, Birmingham, UK. jonathan.ross@bscht.wmids.nhs.uk

OBJECTIVES: To compare the seroprevalence of hepatitis A in homosexual and
heterosexual men to determine their susceptibility to infection and provide
guidance for a policy on vaccination. METHODS: A case-control study design was
utilised to compare the risk factors associated with hepatitis A in homosexual
and heterosexual men attending a city centre genitourinary medicine clinic.
Demographic and sexual behavioural characteristics were included in univariate
and multivariate models. RESULTS: The overall seropositivity rate was 29% with no
significant difference between homosexual and heterosexual men. Ethnicity and age
were strongly associated with hepatitis A seropositivity in both homosexuals and 
heterosexuals. A history of sex in a sauna in homosexual men, and being born
outside the United Kingdom for heterosexual men, was associated with hepatitis A 
seropositivity. CONCLUSIONS: Targeted hepatitis A screening and vaccination of
homosexual men attending UK genitourinary medicine clinics is not supported by
the results of this study.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12238647 [PubMed - indexed for MEDLINE]

565: Pediatr Infect Dis J. 2002 Jul;21(7):618-22.

Seroepidemiology of hepatitis A antibodies among children's hospital staff.

Livni G, Plotkin S, Yuhas Y, Chodik G, Aloni H, Lerman Y, Ashkenazi S.

Department of Pediatrics A, Schneider Children's Medical Center, Petah Tikva,
Israel.

BACKGROUND: With improved socioeconomic conditions, adults are more frequently
seronegative for hepatitis A virus (HAV) and therefore susceptible to infection. 
A safe and efficacious active HAV vaccine has been developed and licensed. The
general recommendation is to vaccinate populations at increased occupational
exposure to HAV. AIM: To determine the seroprevalence of HAV antibodies among
children's hospital employees and to correlate seropositivity with demographic
and occupational variables as a basis for formulating vaccine recommendations.
METHODS: The staff of a tertiary pediatric medical center participated by
answering a structured questionnaire on demographic and occupational data and by 
donating venous blood for determining HAV antibodies by an enzyme immunoassay.
Univariate and multivariate analyses were conducted to identify variables
associated with HAV seropositivity. RESULTS: HAV antibodies were found in 48.3%
of the 499 employees studied, being lowest in pediatricians (38.7%), and
increased with years of work at the hospital, job percentage and contact with
pediatric patients. However, multivariate analysis showed that only the
sociodemographic variables (age and crowding during childhood) were independently
and significantly associated with seropositivity. CONCLUSIONS: HAV seropositivity
was associated mainly with sociodemographic variables. Most children's hospital
employees, especially pediatricians and other young (<40 years) employees, are
seronegative and therefore susceptible to HAV. Vaccination of the high risk
groups should be considered.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 12237591 [PubMed - indexed for MEDLINE]

566: Acta Paediatr. 2002;91(8):882-4.

Decline of maternal hepatitis A virus antibody levels in infants.

De Silvestri A, Avanzini MA, Terulla V, Zucca S, Polatti F, Belloni C.

Divisione Neonatologia-Patologia Neonatale, IRCCS Policlinico S. Matteo Pavia,
Italy.

Hepatitis A is a common viral infection causing substantial morbidity and
mortality. The anti-hepatitis A virus (HAV) vaccination in infants would
guarantee control of the infection. However, the immunogenicity of the HAV
vaccine in infants could be impaired by the presence of passively acquired
maternal HAV antibodies. This study evaluated the prevalence of HAV antibodies in
103 women at delivery and in their babies in the first year of life. Eighteen
mothers (17.5%) had anti-HAV serum level >10 mIU ml(-1). In their infants the
anti-HAV level was still positive in 11 out of 18 (61.1%) at 12 mo. Two out of 85
infants born to anti-HAV-negative mothers and anti-HAV negative at birth were
found to be positive at 5 mo of age. Conclusion: It is proposed that all women be
screened at delivery for anti-HAV antibodies. Children born to anti-HAV-negative 
mothers could be vaccinated early during the first year of life, whereas
vaccination could be postponed in children born to anti-HAV-positive mothers, if 
necessary.

PMID: 12222709 [PubMed - indexed for MEDLINE]

567: Mem Inst Oswaldo Cruz. 2002 Jul;97(5):637-40. Epub 2002 Aug 30.

Seroepidemiological markers of enterically transmitted viral hepatitis A and E in
individuals living in a community located in the North Area of Rio de Janeiro,
RJ, Brazil.

Santos DC, Souto FJ, Santos DR, Vitral CL, Gaspar AM.

Departamento de Virologia, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, RJ,
21045-900, Brasil. dcmoraes@zipmail.com.br

We investigated the seroprevalence of hepatitis A virus (HAV) and hepatitis E
virus (HEV) infection in subjects living in the community of Manguinhos, Rio de
Janeiro, Brazil, and assisted at the Health Unit of Escola Nacional de Saúde
Pública, Fundação Oswaldo Cruz. After formal consent, individuals were submitted 
to an interview using a standardized questionnaire. Anti-HAV and anti-HEV
antibodies were detected by ELISA. Statistical analysis was carried out using the
Epi-Info 6.04b software, to investigate possible associations between serological
markers and risk factors. Results were regarded as significant when p value <
0.05. Although a high prevalence of anti-HAV was observed (87%), almost 50% of
subjects under the age of 10 were susceptible to HAV infection, an unexpected
rate in endemic areas. This fact could be attributed to improvements in
environmental sanitation, occurring in this area in the last years. The
increasing proportion of susceptible people may result in outbreaks of HAV
infection, since the virus still circulates in this area, as verified by the
detection of anti-HAV IgM in some individuals. No statistical association was met
between HAV infection and the risk factors here assessed. The anti-HEV IgG
prevalence found in this population was 2.4%, consistent with the one found in
non-endemic areas.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12219125 [PubMed - indexed for MEDLINE]

568: Med Sci Monit. 2001 May;7 Suppl 1:207-11.

Autoimmune hepatitis in the course of chronic HAV--four year observation.

Woźniakowska-Gesicka T, Kupś J, Wiśniewska-Ligier M, Wróblewska W, Sułat-Syncerek
D, al-Batool K.

3rd Department of Paediatrics, Polish Mother's Memorial Hospital, ul. Rzgowska
281/289, 93-338 Łódź, Poland.

The paper presents a case of a 17-year-old girl with type 1 autoimmune hepatitis 
in whom biochemical, serological and histopathological markers of chronic
hepatitis A were observed for the last 4 years. The diagnosis was based on
elevated levels of gammaglobulins, IgG and the presence of autoantibodies (ANA,
SMA). At first, the patient was treated with the pulses of corticosteroids and
then, as no improvement was observed, continuous steroid therapy was involved.
Relatively mild clinical course of the disease and good response to treatment
with prednisone were recorded. Our observations suggest that HAV is capable of
inducing autoimmune reactions and they indicate possible development of chronic
hepatitis A.

Publication Types: 
    Case Reports

PMID: 12211721 [PubMed - indexed for MEDLINE]

569: Epidemiol Infect. 2002 Aug;129(1):113-7.

An outbreak of hepatitis A among homosexuals linked to a family outbreak.

Stene-Johansen K, Jenum PA, Hoel T, Blystad H, Sunde H, Skaug K.

Department of Virology, National Institute of Public Health, Oslo, Norway.

Several outbreaks of hepatitis A occurred in Norway in 1995-8. Molecular
epidemiology was used to follow the spread of hepatitis A virus in the
population. Distinct strains of hepatitis A virus (HAV) were detected by reverse 
transcriptase-polymerase chain reaction (RT-PCR) and subsequent sequencing in
serum from patients in different communities at risk of infection. Two HAV
strains were detected in an outbreak among 26 men having sexual contact with
other men. One of these strains was also detected in a geographically limited
family outbreak. The family outbreak was first believed to be acquired abroad.
The sequence information linked the two outbreaks, and epidemiological and
serological analyses revealed the transmission route. This study demonstrates the
importance of molecular epidemiology in outbreak investigation, surveillance and 
monitoring of hepatitis A in the population.

PMID: 12211577 [PubMed - indexed for MEDLINE]

570: J Med Virol. 2002 Sep;68(1):7-11.

Prolonged hepatitis A infection in an HIV-1 seropositive patient.

Costa-Mattioli M, Allavena C, Poirier AS, Billaudel S, Raffi F, Ferré V.

Laboratorie de Virologie, Institut de Biologie, CHU Nantes, Nantes, France.

Hepatitis A virus (HAV) is a worldwide disease; in most cases, it causes an acute
self-limited illness that does not lead to a chronic state. The course of HAV
viremia in a homosexual male with human immunodeficiency virus type 1 (HIV-1) and
the correlation between HIV and HAV viral load, alanine aminotranferase (ALT)
level, and CD4(+) lymphocyte count were investigated during the course of the
infection. HAV RNA was detected quantitatively up to 256 days after clinical
onset. To our knowledge, this specific case is the first report of a prolonged
infection with hepatitis A in a male with HIV-1. The ALT levels decreased
gradually; however, 286 days after clinical onset of hepatitis, ALT levels were
three times higher than normal values. HIV viral load was not affected by the
infection with HAV and CD4(+) cell count was stable during the course of the
co-infection. The duration and the high-titer viremia of hepatitis A virus in an 
immunodeficient patient constitute a serious risk of the spread of hepatitis A
within this population. As inactivated HAV vaccine is safe in HIV-positive
subjects, it would be wise to establish a strategy of preventive vaccination in
this high-risk group. Copyright 2002 Wiley-Liss, Inc.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't

PMID: 12210424 [PubMed - indexed for MEDLINE]

571: J Med Virol. 2002 Oct;68(2):168-74.

Genetic characterization of hepatitis A virus isolates from Buenos Aires,
Argentina.

Mbayed VA, Sookoian S, Alfonso V, Campos RH.

Cátedra de Virología, Facultad de Farmacia y Bioquímica, Universidad de Buenos
Aires, Buenos Aires, Argentina. vmbayed@ffyb.uba.ar

The Hepatitis A virus (HAV) has been classified in seven different genotypes,
which include human (I, II, III, and VII) and simian (IV, V, and VI) groups. The 
sequence analysis of HAV strains contributes to the molecular epidemiology of the
virus. Although the infection with HAV is endemic in Argentina and vaccination is
being implemented in this country, using both IA and IB strains, there are very
few data on the genotypes of the circulating viruses. On the basis of the
sequences of 20 isolates collected in Buenos Aires during a 2-year period
(extended to 3 years by two additional specimens), we observed the presence of a 
single sub-genotype, IA, but with a high genetic diversity. We analyzed the
VP1-2A junction and also the VP3-VP1 region. Most of the Argentine isolates
grouped in at least two clusters. One of these was related to South American
strains, thus suggesting a co-circulation of related isolates in neighbor
countries. The other cluster was composed only of Argentine specimens. Other
sequences were more scattered along the phylogenetic tree. However, we
demonstrated that a consistent genetic relatedness of sequences could only be
inferred on the basis of a more extensive sequencing of each isolate. Copyright
2002 Wiley-Liss, Inc.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12210404 [PubMed - indexed for MEDLINE]

572: Pharmacoeconomics. 2002;20(11):739-47.

Valuation of symptomatic hepatitis a in adults: estimates based on time trade-off
and willingness-to-pay measurement.

Jacobs RJ, Moleski RJ, Meyerhoff AS.

Capitol Outcomes Research, Inc, Alexandria,Virginia 22310, USA.
Jake.Jacobs@CapitolOutcomesResearch.com

BACKGROUND: The cost effectiveness of hepatitis A prevention is typically
assessed by comparing vaccination costs with the number of life-years saved. This
endpoint does not consider the benefits of preventing nonfatal yet symptomatic
infections. Nearly as many days of healthy life are lost to hepatitis A morbidity
as mortality. OBJECTIVE: To investigate the value American adults place on
preventing hepatitis A symptoms by using the willingness-to-pay and time
trade-off metrics. METHODS: We provided a written description of hepatitis A
symptoms to 181 American adults, who judged the amounts of money and lifespan
they would forego to avoid them. The description made no reference to the
possibility of fatality, and respondents were asked not to consider costs of
medical care and work loss. We investigated relationships between demographic
characteristics and each metric, the relationship between the two metrics, and
the test/re-test reliability of the metrics. RESULTS: Respondents would pay a
median of dollars US 2000 (inter-quartile range, dollars US 500 to 5000; 2001
values) for risk-free prevention of hepatitis A symptoms. Alternatively, they
would forego a median of 28 days survival (inter-quartile range, 6 to 40 days)
for cost-free prevention. There was modest correlation between willingness-to-pay
and time trade-off responses (r = 0.24, p < 0.01), suggesting these metrics
measure independent aspects of preference. Strong correlations between measures
obtained 30 days apart support the test/re-test reliability of willingness to pay
(r = 0.70, p < 0.01) and time trade-off (r = 0.73, p < 0.01) metrics. In
multivariate analyses, higher household income (p = 0.02) predicted greater
willingness to pay in dollars. Male gender (p < 0.01) predicted greater
willingness to forego life expectancy for better health. CONCLUSION: In our study
population of US adults, most were willing to pay or trade life expectancy for a 
hypothetical preventative drug for hepatitis A symptoms. The amount respondents
were willing to pay appears dependent on their income level while males are
willing to trade more life expectancy than female respondents. The values
expressed should be considered in assessments of hepatitis A prevention.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12201793 [PubMed - indexed for MEDLINE]

573: Semin Pediatr Infect Dis. 2002 Jul;13(3):165-73.

Hepatitis A vaccine.

Bell BP.

Epidemiology Branch, National Center for Infectious Diseases, Centers for Disease
Control and Prevention, Atlanta, GA 30333, USA.

Hepatitis A is an infectious disease frequently reported in the United States. An
average of 26,000 cases were reported each year during 1980 to 1999; probably 3
times as many occurred. Hepatitis A vaccines provide a powerful new prevention
tool. The 2 inactivated hepatitis A vaccines available as pediatric and adult
formulations in the United States and in many other countries are safe,
immunogenic, and efficacious. A single dose provides excellent short-term
protection; the second dose is thought to be important for long-term protection. 
Because hepatitis A virus (HAV) is excreted in high concentrations in the stool, 
the principal mode of transmission is person-to-person by the fecal-oral route,
most commonly among household and sexual contacts of people with HAV infection.
Children can be important in transmission because they frequently have
unrecognized or asymptomatic infection. Implementation of recommendations for
routine hepatitis A vaccination of children living in areas with consistently
elevated hepatitis A rates appears to be resulting in dramatic declines in the
overall incidence of the disease. Improved vaccination coverage and continued
monitoring of incidence rates are needed to determine the overall long-term
impact of this strategy.

Publication Types: 
    Review

PMID: 12199612 [PubMed - indexed for MEDLINE]

574: South Med J. 2002 Aug;95(8):826-33.

Hepatitis A epidemic in the elderly.

Brown GR, Persley K.

Department of Internal Medicine, University of Texas Southwestern Medical Center 
at Dallas, 75390-9151, USA.

BACKGROUND: The purpose of this study was to characterize acute hepatitis A in
patients more than 40 years old. METHODS: Retrospective chart reviews and
physician questionnaires were used. Hospitalization, laboratory tests, comorbid
conditions, complications, and mortality were assessed. RESULTS: A total of 180
cases of acute hepatitis A occurred in patients more than age 40. Hospitalization
rates increased from 3% for the group aged 40 to 49 to 12% in the group aged 50
to 69 and 42% in those > or = 70 years old. The mean peak total bilirubin value
was higher in hospitalized patients than in nonhospitalized patients (12.4 mg/dL 
vs 7.7 mg/dL). Comorbid conditions included significant alcohol consumption (8%),
diabetes (16.6%), cardiovascular disease (54%), and chronic obstructive pulmonary
disease (COPD) (21%). Complications included pancreatitis (4.1%), ascites (8.3%),
prolonged cholestatic features (7.6%), and death (0.8%). CONCLUSION:
Hospitalization rates and rare complications associated with acute hepatitis A
increase with age.

PMID: 12190216 [PubMed - indexed for MEDLINE]

575: J Virol. 2002 Sep;76(18):9516-25.

Molecular evolution of hepatitis A virus: a new classification based on the
complete VP1 protein.

Costa-Mattioli M, Cristina J, Romero H, Perez-Bercof R, Casane D, Colina R,
Garcia L, Vega I, Glikman G, Romanowsky V, Castello A, Nicand E, Gassin M,
Billaudel S, Ferré V.

Laboratorie de Virologie UPRES-EA1156, Institut de Biologie, Centre Hospitalier
Regional Universitaire de Nantes, 44093 Nantes, France.

Hepatitis A virus (HAV) is a positive-stranded RNA virus in the genus Hepatovirus
in the family Picornaviridae So far, analysis of the genetic variability of HAV
has been based on two discrete regions, the VP1/2A junction and the VP1 N
terminus. In this report, we determined the nucleotide and deduced amino acid
sequences of the complete VP1 gene of 81 strains from France, Kosovo, Mexico,
Argentina, Chile, and Uruguay and compared them with the sequences of seven
strains of HAV isolated elsewhere. Overall strain variation in the complete VP1
gene was found to be as high as 23.7% at the nucleotide level and 10.5% at the
amino acid level. Different phylogenetic methods revealed that HAV sequences form
five distinct and well-supported genetic lineages. Within these lineages, HAV
sequences clustered by geographical origin only for European strains. The
analysis of the complete VP1 gene allowed insight into the mode of evolution of
HAV and revealed the emergence of a novel variant with a 15-amino-acid deletion
located on the VP1 region where neutralization escape mutations were found. This 
could be the first antigenic variant of HAV so far identified.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12186933 [PubMed - indexed for MEDLINE]

576: Eur J Gastroenterol Hepatol. 2002 Aug;14(8):877-8.

Generalized lymphadenopathy as a marker of ongoing inflammation in prolonged
cholestatic hepatitis A.

Mukhopadhya A, Chandy GM.

Department of Clinical Gastroenterology and Hepatology, Christian Medical College
Hospital, Vellore, Tamilnadu, India. ashis@angelfire.com

Extrahepatic manifestations of hepatitis A are very unusual. We describe a case
of prolonged cholestatic hepatitis A in a patient with generalized
lymphadenopathy. With normalization of transaminases, there was an accompanying
reduction in size of these lymph nodes. Lymphadenopathy reflects ongoing hepatic 
inflammation in prolonged cholestatic hepatitis A.

Publication Types: 
    Case Reports

PMID: 12172409 [PubMed - indexed for MEDLINE]

577: J Trop Pediatr. 2002 Jun;48(3):180-2.

The prevalence of antibodies to hepatitis A among preschool children in an urban 
setting in Turkey.

Ungan M, Yaman H, Taheri N.

Middle East Technical University Medical Center, Department of Family Medicine,
Ankara, Turkey. mungan@metu.edu.tr

The prevalence of antibodies to hepatitis A virus (HAV) was investigated in 114
children (59.7 per cent males) aged 4-6 years, in the campus area of Middle East 
Technical University, Ankara, Turkey. The prevalence of hepatitis A antibody in
this age group was 11.4 per cent (13/114). The rate of immunized children against
hepatitis A was 3.65 per cent (5/137). In conclusion the prevalence of anti-HAV
demonstrates the susceptibility of other preschool children to hepatitis A. This 
may be a cause for considering hepatitis A vaccination before preschool
attendance in Turkey.

PMID: 12164604 [PubMed - indexed for MEDLINE]

578: J Gastroenterol. 2002;37(7):517-22.

Severe manifestation of acute hepatitis A recently found in Gunma, Japan.

Kanda D, Takagi H, Hashimoto Y, Yamazaki Y, Matsui M, Kosone T, Arai H, Ichikawa 
T, Nakajima H, Otsuka T, Kojima A, Sato K, Kakizaki S, Matsuzaki Y, Matsumoto T, 
Shimoda R, Kaneko M, Takayama H, Takahashi H, Abe T, Takezawa J, Mori M.

The First Department of Internal Medicine, Gunma University School of Medicine,
Showa, Maebashi, Japan.

BACKGROUND: The incidence of acute hepatitis A infection in Japan peaked 10 years
ago and has been decreasing since then. However, an increase in severe cases of
the disease has been documented recently. We experienced an outbreak in
1998-1999, and compared the clinical features of the disease in 1998-1999 (recent
outbreak) and in 1987-1988 (past outbreak) in our prefecture (Gunma). METHODS:
Forty patients with acute hepatitis A were admitted to nine Gunma hospitals from 
October 1998 to September 1999. Their clinical features were compared with those 
of 100 patients with acute hepatitis A admitted to the same hospitals in
1987-1988. RESULTS: Both outbreaks occurred mostly during the winter-spring
season. Secondary familial infection was significantly decreased in the recent
outbreak. Patients in the recent outbreak were 7 years older than those in the
past outbreak. Laboratory findings, such as serum aspartate aminotransferase
(AST) and alanine aminotransferase (ALT) levels and prothrombin time, were worse 
in the recent than in the past outbreak. Severe-type hepatitis and fulminant
hepatitis occurred in 5 patients (12.5%) in the recent outbreak but in only 2
patients (2.0%) in the past outbreak. CONCLUSIONS: Clinical data and
manifestations were more severe in the recent outbreak than in the past outbreak 
of acute hepatitis A. It is important to be aware of hepatitis A virus infection 
and to take into account the available vaccination against hepatitis A virus in
Japan.

PMID: 12162409 [PubMed - indexed for MEDLINE]

579: Hepatology. 2002 Aug;36(2):474-8.

Hepatitis E virus superinfection in patients with chronic liver disease.

Hamid SS, Atiq M, Shehzad F, Yasmeen A, Nissa T, Salam A, Siddiqui A, Jafri W.

Department of Medicine, The Aga Khan University, Karachi, Pakistan.
saed.hamid@aku.edu

Infection with hepatitis A virus (HAV) can cause severe illness in adult patients
with chronic liver disease (CLD) caused by hepatitis C. In endemic areas such as 
South Asia, however, most adult patients already have been exposed to HAV but
could still be susceptible to hepatitis E virus (HEV) infection. We document that
HEV superinfection in 4 of our CLD patients caused severe liver decompensation.
We then determined the seroprevalence of HAV and HEV in 233 patients with stable 
CLD, with the goal of defining the need for protection against these viruses in
these patients. Overall, 41 (17.5%) of 233 CLD patients were HEV antibody
immunoglobulin G (IgG)-positive, and 228 of 233 (97.8%) were HAV IgG-positive. As
controls, we tested 90 age- and sex-matched healthy volunteer blood donors for
HAV and HEV antibodies IgG. There was no difference in the percentage of CLD
patients and blood donors positive for HEV antibody IgG (17.7% vs. 17.5%) or for 
HAV IgG (97.8% vs. 94%). No differences were observed in the severity of liver
disease between previously HEV-exposed and -nonexposed patients. In conclusion,
superinfection with HEV in patients with underlying CLD can cause severe hepatic 
decompensation leading to increased morbidity and mortality. The large majority
of adult CLD patients in endemic countries are vulnerable to infection with HEV, 
but are protected against hepatitis A, and are ideal candidates for an HEV
vaccine.

Publication Types: 
    Case Reports

PMID: 12143058 [PubMed - indexed for MEDLINE]

580: Ann Allergy Asthma Immunol. 2002 Jul;89(1):99-100.

Incidental asthma prevention by immune serum globulin.

Mimouni D, Gdalevich M, Mimouni K, Mimouni FB, Eldad A, Shpilberg O.

Johns Hopkins University, School of Medicine, Department of Dermatology,
Baltimore, Maryland 21205, USA. dmimoun1@jhmi.edu

BACKGROUND: After a case of hepatitis A in a food handling worker in a military
base, the entire exposed population was vaccinated with immune serum globulin
(ISG). We analyzed the potential effects of ISG on asthma attacks and respiratory
infections. METHODS: The base population was observed for asthma exacerbation for
the 3 months after the immunization and was compared with the population of the
same base a year earlier. Rates were tested using chi2 statistics. RESULTS: The
vaccinated population had a highly significant decrease in the incidence of
asthma attacks (rate ratio [RR] = 0.2, 95% confidence interval [CI] 0.09 to
0.45), sinusitis (RR = 0.34, 95% CI 0.2 to 0.58), and pneumonia (RR = 0.41, 95%
CI 0.17 to 0.99). No significant difference was observed in the incidence rates
of upper respiratory infections between the two groups. CONCLUSIONS: A single
administration of ISG significantly reduces the rate of asthma attacks and
respiratory infections.

PMID: 12141729 [PubMed - indexed for MEDLINE]

581: Indian J Pediatr. 2002 Jun;69(6):535-6.

Vertical transmission of hepatitis A.

Renge RL, Dani VS, Chitambar SD, Arankalle VA.

Dept. of Pediatrics, Indira Gandhi Medical College, Nagpur, India.

Two hospital delivered full term newborn babies were detected to have cholestatic
jaundice in the first week of life. They had raised liver enzyme levels, which
gradually declined over a period of one month. Both babies were anti HAV IgM
positive on 6th day of life in Case 1 and on 7th day of life in Case 2
respectively. Both the mothers had jaundice 20 and 26 days before delivery and
had anti HAV IgM positivity two and three weeks prior to delivery in Case 1 and 2
respectively. Hepatitis A virus is not transmitted vertically from mother to
baby. However, there are 3 such case reports in literature stating vertical
transmission of HAV infection. We are reporting it in two neonates for the first 
time in India.

Publication Types: 
    Case Reports

PMID: 12139145 [PubMed - indexed for MEDLINE]

582: Am J Gastroenterol. 2002 Jul;97(7):1792-5.

Comment in:
    Am J Gastroenterol. 2002 Jul;97(7):1590-3.

Prescreening versus empirical immunization for hepatitis A in patients with
chronic liver disease: a prospective cost analysis.

Duncan M, Hirota WK, Tsuchida A.

OBJECTIVES: There are few prospective studies estimating the prevalence of
hepatitis A in chronic liver disease patients. Furthermore, there are minimal
cost-comparative data as to whether or not screening for hepatitis A exposure
before immunization is an effective fiscal strategy. The objectives of this study
were to determine the prevalence of prior hepatitis A infection and to perform a 
prospective cost analysis for hepatitis A immunization in patients with chronic
liver disease. METHODS: This is a prospective cohort study of 100 patients with
chronic liver diseases. Patients were screened for potential risk factors for
hepatitis A including history of jaundice, socioeconomic status, birth origin,
and ethnic background. Each patient underwent testing for evidence of prior
infection using an ELISA. Seronegative patients then went on to receive an
immunization series. Cost analysis of vaccination without prescreening (universal
strategy) was compared to cost analysis of prescreening and selective
immunization of those without prior infection (selective strategy). RESULTS:
Fifty-three patients (53%) had serological evidence of prior hepatitis A
infection (95% CI = 43-63%). Of the risk factors assessed, foreign birth was
associated with prior hepatitis A exposure (p = 0.0002). Cost analysis revealed
that prescreening for hepatitis A before vaccination was cost saving given the
current prevalence. CONCLUSIONS: The seroprevalence of hepatitis A in those with 
chronic liver diseases was 53%. Cost analysis revealed that screening for
hepatitis A before immunization is cost saving, and this strategy should be
applied to follow current vaccination guidelines.

Publication Types: 
    Comparative Study
    Research Support, U.S. Gov't, Non-P.H.S.

PMID: 12135037 [PubMed - indexed for MEDLINE]

583: Asian Pac J Allergy Immunol. 2002 Mar;20(1):53-6.

Declining hepatitis A seroprevalence among medical students in Bangkok, Thailand,
1981-2001.

Chatchatee P, Chongsrisawat V, Theamboonlers A, Poovorawan Y.

Department of Pediatrics, Faculty of Medicine, Chulalongkorn University and
Hospital, Bangkok, Thailand.

The severity of clinical symptoms following hepatitis A virus (HAV) infection is 
age dependent. Hepatitis A in children is mostly an asymptomatic disease while
adolescents and adults usually show symptoms of clinical hepatitis. Improved
personal hygiene and environmental sanitation has led to a decline in natural
immunity acquired in childhood, creating a population of susceptible adults. In
the past decade, the incidence and prevalence of hepatitis A disease in Thailand 
have decreased significantly. In this study, we used enzyme-linked immunosorbent 
assay to determine the prevalence of anti-HAV antibodies among medical students
at two different time points in 1996 and 2001. We then compared these results
with data from previous studies in 1981 and 1992. The seroprevalence was 73.01%, 
30.23%, 16.67% and 6.67% in 1981, 1992, 1996 and 2001, respectively. A
significant decline has happened over the past two decades (p < 0.001).
Considering the decreasing immunity to HAV in the younger generations, more cases
of symptomatic HAV infection could be anticipated. Further seroprevalence studies
in other adolescence groups from different socioeconomic status are needed to
elucidate the current situation of HAV infection in the young generation more
comprehensively and to develop an appropriate prevention program.

Publication Types: 
    Clinical Trial
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 12125918 [PubMed - indexed for MEDLINE]

584: Southeast Asian J Trop Med Public Health. 2002 Mar;33(1):118-27.

Cost-benefit analysis of hepatitis a vaccination in Thailand.

Teppakdee A, Tangwitoon A, Khemasuwan D, Tangdhanakanond K, Suramaethakul N,
Sriratanaban J, Poovorawan Y.

Department of Pediatrics, Faculty of Medicine, Chulalongkorn University and
Hospital, Bangkok, Thailand.

We constructed a decision model to simulate costs and benefits for persons in the
context of hepatitis A prevention. Three strategies were compared: i) no
intervention; ii) vaccination against hepatitis A without screening; iii)
vaccination against hepatitis A for those susceptible after screening for
anti-HAV. We divided the population into 3 age groups : 3-11 years, 12-18 years
and 19-40 years. Data regarding the cost of treatment and vaccination were
obtained from the King Chulalongkorn Memorial Hospital. Relevant probabilities
were obtained from published literature and expert opinion. At the present
incidence of hepatitis A infection, in all age groups examined, the net benefits 
of a universal no-intervention strategy were higher than those of either
vaccination (intervention) strategy. The cost of vaccination without screening in
the 3-11-year and 12-18-year groups would equal the benefit if the incidence
rates amounted to approximately 138 and 212 infected individuals per 100,000,
respectively, that of vaccination with screening at incidence rates of about 200 
and 260 infected persons per 100,000, respectively. In the 19-40-year group, the 
cost incurred by vaccination either with or without screening would equal the
benefit at an incidence rate above 450 infected individual per 100,000. For the
benefits to outweigh the estimated vaccination costs at present the vaccine is
still too expensive. The cost of vaccination without screening in the 3-11-year
group would equal the benefit if the cost of vaccine was about 586 baht/2 doses
(293 baht/dose), and about 500 baht/2 doses (250 baht/dose) in the 12-18-year
group. Likewise, because of the cost of vaccine, it would not be cost-beneficial 
in the 19-40-year group both with and without screening, and neither would it be 
in the 3-11-year and 12-18-year groups including screening. According to current 
standards, under the conditions of the present study the benefit of hepatitis A
vaccination administered to the general population between the age of 3 and 40
years in Thailand does not justify the expenses incurred. Major changes in
hepatitis A incidence, anti-HAV seroprevalence, vaccine cost or the treatment
outcome would be required to potentially render either intervention strategy cost
beneficial.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12118439 [PubMed - indexed for MEDLINE]

585: Epidemiol Infect. 2002 Jun;128(3):457-63.

The changing epidemiological pattern of hepatitis A in England and Wales.

Morris MC, Gay NJ, Hesketh LM, Morgan-Capner P, Miller E.

Immunisation Division, PHLS Communicable Disease Surveillance Centre, London.
MMorris@phls.org.uk

Sera from an age-stratified sample of 4188 individuals, submitted for diagnostic 
purposes to 15 public health laboratories in England and Wales in 1996, were
tested for hepatitis A antibody. The serological profiles were consistent with
declining incidence in the past. This hypothesis was tested by comparing the
serological profiles of Ashford, Leeds and Preston public health laboratories
with those from sera collected during a previous study in the same laboratories
in 1986/7. A comparison of equivalent 10 year birth cohorts revealed that
significant hepatitis A seroconversion had only continued in Ashford. However, it
is probable that most seroconversions are due to vaccination and immigration
rather than continuing viral transmission. Further population-based surveys
collecting more in-depth social and demographic data are needed to confirm the
main factors influencing hepatitis A seroprevalence and to explain the regional
differences.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12113490 [PubMed - indexed for MEDLINE]

586: Clin Diagn Lab Immunol. 2002 Jul;9(4):840-5.

Evaluation of urine as a clinical specimen for diagnosis of hepatitis a.

Joshi MS, Chitambar SD, Arankalle VA, Chadha MS.

Hepatitis Division, National Institute of Virology, Pune, 411 001 India.

The present study pertains to the evaluation of urine as a specimen for detection
of anti-hepatitis A virus (anti-HAV) antibodies. Immunoglobulin M (IgM), IgG, and
IgA capture enzyme-linked immunosorbent assays for hepatitis A were performed on 
paired serum and urine specimens collected from hepatitis A patients (n = 92),
healthy individuals (n = 100), non-A hepatitis patients (n = 70), and patients
with nonhepatic diseases (n = 64, including 37 renal disease patients). Hepatitis
A patients seropositive for anti-HAV IgM showed 95.65% uropositivity. No
false-positive reactions were observed in control groups. The uropositivity of
anti-HAV IgM persisted during the convalescent phase of the disease. Anti-HAV IgG
uropositivity correlated well with corresponding seropositivity in all groups (P 
> 0.05 for each). No significant difference between the proportions of serum and 
urine positivity for anti-HAV IgA was noted (P > 0.05 for each). Using
seroreactivity as a "gold standard," the sensitivity and specificity for anti-HAV
IgM, anti-HAV IgG, and anti-HAV IgA tests with urine as a specimen were found to 
be 95.65 and 100%, 97.76 and 76.47%, and 92.23 and 88.18%, respectively. Urine
appears to be comparable to serum for diagnosis of recent and past infection with
hepatitis A.

Publication Types: 
    Comparative Study

PMID: 12093683 [PubMed - indexed for MEDLINE]

587: J Travel Med. 2002 May-Jun;9(3):122-6.

Combined vaccination against hepatitis A, hepatitis B, and typhoid fever: safety,
reactogenicity, and immunogenicity.

Proell S, Maiwald H, Nothdurft HD, Saenger R, Vollmar J, De Clercq N, von
Sonnenburg F.

Abteilung für Infektions- und Tropenmedizin, Klinikum Innenstadt der
Ludwigs-Maximilians-Universität München, Germany.

BACKGROUND: The etiological agents of hepatitis A, hepatitis B, and typhoid fever
share similar patterns of global distribution, and cause significant disease
burden in travelers to endemic countries. Combined vaccination against all three 
diseases, based on currently available vaccines, would promote compliance and
convenience for travelers. This clinical study evaluated the feasibility of
extemporaneously syringe-mixed hepatitis A and B vaccine (Twinrix) and a Vi
polysaccharide vaccine (Typherix) in healthy adults, and compared this to
concomitant administration of the vaccines in separate arms. METHODS: The mixed
dose of vaccine contained at least 720 enzyme-linked immunosorbent assay (ELISA) 
units of the inactivated hepatitis A antigen, 20 microg of the recombinant
hepatitis B antigen and 25 microg of the Vi polysaccharide typhoid antigen in 1.5
mL. The study was conducted in 200 healthy 18- to 45-year-old volunteers.
RESULTS: Equivalence between the vaccines mixed before administration and the
concomitantly administered vaccines was shown in terms of seroconversion and
seroprotection. With the exception of local injection site soreness, which was
higher in the mixed administration group, the reactogencity was similar for both 
groups. In both vaccination groups more than 95% of the subjects were
anti-hepatitis A virus and anti-Vi seropositive 1 month after the first
vaccination. With regard to hepatitis B, a strong response was achieved in both
groups, with more than two-thirds of the subjects protected 2 months after the
start of the immunization course. CONCLUSION: These results support the
feasibility of extemporaneously syringe-mixed combined hepatitis A and B vaccine 
with a Vi polysaccharide typhoid vaccine, administered in healthy adults.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial

PMID: 12088576 [PubMed - indexed for MEDLINE]

588: Infect Control Hosp Epidemiol. 2002 Jun;23(6):343-5.

A nosocomial and occupational cluster of hepatitis A virus infection in a
pediatric ward.

Petrosillo N, Raffaele B, Martini L, Nicastri E, Nurra G, Anzidei G, Ippolito G.

National Institute for Infectious Diseases, Lazzaro Spallanzani, IRCCS, Rome,
Italy.

We describe a cluster of acute hepatitis A virus (HAV) infection that involved
two patients and one physician in the pediatric unit where two children with
acute HAV infection had been housed. An interview with the unit personnel
revealed several breaches in infection control measures and the lack of
vaccination of healthcare workers against HAV .

PMID: 12083241 [PubMed - indexed for MEDLINE]

589: J Viral Hepat. 2002 Jul;9(4):315-21.

Changing scenario of hepatitis A virus and hepatitis E virus exposure among the
primitive tribes of Andaman and Nicobar Islands, India over the 10-year period
1989-99.

Murhekar MV, Sehgal SC, Murhekar KM, Padbhidri SP, Chitambar SD, Arankalle VA.

Regional Medical Research Centre (ICMR), Port Blair, Andaman and Nicobar Islands,
India, National Institute of Virology (ICMR), Pune, India.

The Andaman and Nicobar Islands, Union Territory of India, are home to six
primitive tribes. Studies carried out earlier among these tribes revealed very
high rates of hepatitis B infection. We have now studied hepatitis A and E
infection among them. A total of 951 serum samples were collected from four
accessible tribes (Nicobarese, Shompens, Onges and Great Andamanese) and tested
for antibodies against hepatitis A and E viruses. In addition, 240 serum samples 
collected a decade earlier from age-stratified Nicobarese were also screened.
Hepatitis A virus (HAV) infection was found to be highly endemic among all the
tribes, whereas hepatitis E virus (HEV) infection was common among the Nicobarese
and Shompens. The age group-wise prevalence of these infections among the
Nicobarese showed different patterns, HAV prevalence rising significantly from
those aged 10 years and thereafter reaching a plateau, whereas HEV prevalence was
found to be more evenly distributed over all age groups, but rising somewhat
after 30 years of age. Over the last decade, the prevalence of HAV among the
Nicobarese has declined slightly, particularly in those aged 10 years or less
whereas HEV infection has more than doubled over all age ranges. Different HEV
prevalence observed among the tribes could not be attributed to differences in
sanitation or water supply. This fact and the different age-wise patterns of HAV 
and HEV prevalences is suggestive of different modes of transmission of HEV that 
are not shared. The highest rates for HEV were among those tribes which reared
pigs suggesting that pigs might serve as reservoir of HEV. Further studies are
needed, however, to validate these findings.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12081610 [PubMed - indexed for MEDLINE]

590: Gut. 2002 Jul;51(1):82-8.

Association between severity of type A hepatitis and nucleotide variations in the
5' non-translated region of hepatitis A virus RNA: strains from fulminant
hepatitis have fewer nucleotide substitutions.

Fujiwara K, Yokosuka O, Ehata T, Saisho H, Saotome N, Suzuki K, Okita K, Kiyosawa
K, Omata M.

First Department of Internal Medicine, Chiba University School of Medicine,
Chiba, Chiba 260-8670, Japan.

BACKGROUND: Type A hepatitis is still a considerable problem in both
underdeveloped and developed countries. Why some patients progress to fulminant
type A hepatitis and others do not is unclear. AIMS: To determine if nucleotide
differences in the genome of hepatitis A virus (HAV) are responsible for the
range of clinical severities, we analysed the 5' non-translated region (5'NTR) of
the HAV genome, which has an internal ribosomal entry site and is important for
cap independent translation of the viral message. METHODS: Serum samples from 84 
Japanese patients with sporadic type A hepatitis from five distant regions of
Japan, comprising 12 patients with fulminant hepatitis (FH), 13 with severe acute
hepatitis (AHs), and 59 with acute hepatitis (AH), were examined for HAV RNA. The
fragment between nucleotides 75 and 638 of the 5'NTR was amplified by reverse
transcription-polymerase chain reaction, and the nucleotide sequence was
determined by direct sequencing. RESULTS: Comparison of sequences of the 5'NTR
revealed relatively fewer nucleotide substitutions in FH and AHs patients
compared with the considerable sequence variations found in strains of AH. This
tendency was most prominent between nucleotides 200 and 500. Strains from FH and 
AHs cases had fewer nucleotide substitutions (p<0.001) in this region.
CONCLUSIONS: Nucleotide variations in the central portion of the 5'NTR of HAV may
influence the severity of type A hepatitis.

PMID: 12077097 [PubMed - indexed for MEDLINE]

591: J Hepatol. 2002 Jul;37(1):131-6.

Polymerase chain reaction-based prevalence of hepatitis A, hepatitis E and TT
viruses in sewage from an endemic area.

Vaidya SR, Chitambar SD, Arankalle VA.

Hepatitis Division, National Institute of Virology, 20-A Dr Ambedkar Road, 411001
Pune, India.

BACKGROUND/AIMS: Hepatitis A and E viruses (HAV, HEV) are transmitted enterically
and are highly endemic in India. This study aims to evaluate prevalence of these 
and TT virus (TTV) in the sewage. METHODS: Influent and effluent samples from a
sewage treatment plant from Pune, India were collected twice a week for 1 year
and subjected to nested polymerase chain reaction (PCR) for the detection of HAV 
RNA, HEV RNA and TTV DNA. HAV and HEV PCR products were sequenced. Effluent
samples were not collected for 5 months as the plant was non-functional. RESULTS:
The overall prevalence was 24.42% (21/86, HAV), 10.98% (9/82, HEV) and 12.7%
(8/63, TTV). Prevalence of HAV was significantly higher than HEV (P=0.023).
During summer months, significantly higher HAV RNA positivity was noted (P<0.01).
A substantial reduction in HAV RNA positivity (15/48 vs. 2/48, P=0.0008) was
recorded for treated sewage samples. However, HEV RNA or TTV DNA positivity did
not reduce significantly. Of the 17 HAV and HEV RNA negative sewage samples
concentrated using ultracentrifugation, 13 and none were positive for HAV and HEV
RNA, respectively. Phylogenetic analyses grouped these viruses in IB and Ia,
respectively, the genotypes most prevalent in India. CONCLUSIONS: Sewage may play
an important role in maintaining hyper-endemicity of these infections. Sustained 
efforts are obligatory to render sewage less/non-infectious.

PMID: 12076872 [PubMed - indexed for MEDLINE]

592: Pediatr Infect Dis J. 2002 Apr;21(4):347-8.

Kinetics of maternal hepatitis a antibody decay in infants: implications for
vaccine use.

Lieberman JM, Chang SJ, Partridge S, Hollister JC, Kaplan KM, Jensen EH, Kuter B,
Ward JI.

Miller Children's Hospital Long Beach, CA 90806, USA. jay_lieberman@hotmail.com

We conducted a seroepidemiologic study to evaluate the kinetics of maternal
hepatitis A antibody decay in infants. Serum samples obtained from 200 infants at
2 and 4 months of age were tested for hepatitis A antibody. Seventy-six infants
(38%) were hepatitis A antibody-positive with a geometric mean antibody titer of 
2634 mIU/ml. Samples collected at 4, 6 and/or 12 months of age showed
seropositivity rates of 100, 95 and 39%, respectively. These data indicate that
maternal antibody levels remained high through the first 6 months of life but
decayed significantly by 12 months of age.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12075769 [PubMed - indexed for MEDLINE]

593: Acta Microbiol Immunol Hung. 2002;49(1):93-7.

Seroprevalence of antibodies to hepatitis A and E viruses in pediatric age groups
in Turkey.

Colak D, Ogunc D, Gunseren F, Velipasaoglu S, Aktekin MR, Gültekin M.

Department of Clinical Microbiology, Akdeniz University Medical School, Antalya, 
Turkey.

Hepatitis A and hepatitis E are enteric transmitted viral diseases occurring in
epidemic and sporadic forms especially in developing countries. Previous studies 
in Turkey showed that most residents are infected with HAV by the second decade
of life. Since HEV is generally transmitted by the same route as HAV we conducted
a community-based seroprevalence study for HAV and HEV infection in Ahatli area
in Antalya, Turkey where socioeconomic conditions are low. Anti-HAV total
immunoglobulin was tested by using a microparticle EIA (Axsym-Abbott Lab).
Anti-HEV IgG was assayed by a micro ELISA method (Genelabs-Singapore). Of the 338
sera tested, 112 (33.1%) were positive for anti-HAV total antibody. Anti-HEV IgG 
was detected in three (0.89%) of the serum samples. Seropositivity rates of HAV
in preschool and school children were 19.9% and 43.9% respectively (p < 0.001).
No antibody to HEV was detected in preschool children, while the prevalence of
anti-HEV IgG was 1.6% in children attending school. Our data showed that
seroprevalence of anti-HAV is high among children samples but HEV infection
appears to be relatively rare in pediatric age groups.

PMID: 12073829 [PubMed - indexed for MEDLINE]

594: Am J Ment Retard. 2002 Jul;107(4):278-92.

Prevalence of hepatitis virus infections in an institution for persons with
developmental disabilities.

Woodruff BA, Vazquez E.

Department of Viral Hepatitis, Centers for Disease Control and Prevention,
Atlanta, GA 30333, USA. baw4@cdc.gov

In 1994-1995, we collected medical and serologic data on viral hepatitis
infection on 1,235 residents of Sonoma Developmental Center. Residents were
mostly White and had lived in the Center over 10 years. Only 3 residents (.3%)
had hepatitis C virus infection, and 633 (60.2%) had past or current hepatitis B 
virus infection. The prevalence of hepatitis B virus infection rose rapidly with 
longer residence in institutions. Past hepatitis A virus infection had occurred
in 494 residents (42.1%). The rise in its prevalence with duration of residence
was much less than that seen with hepatitis B virus infection. Although hepatitis
C virus infection was relatively rare at the Center, many residents had past
hepatitis A and hepatitis B virus infections.

PMID: 12069647 [PubMed - indexed for MEDLINE]

595: Dig Dis Sci. 2002 Jun;47(6):1183-94.

Hepatitis A, hepatitis B, and combination hepatitis vaccines for
immunoprophylaxis: an update.

Koff RS.

Department of Medicine, University of Massachusetts Medical School, Worcester,
USA.

Since the publication of the last extensive review of hepatitis vaccines, use of 
inactivated hepatitis A vaccines has been extended to high-risk regions of the
United States and specific patient groups, such as those with chronic liver
disease, and use of the recombinant hepatitis B vaccines has been recommended for
older adolescents. A combination hepatitis A and B vaccine, recently approved for
licensure by the US Food and Drug Administration, should increase convenience and
compliance, reduce the costs of vaccination, and provide prolonged and dual
protection for those at risk for hepatitis. Although commercially available
vaccines for hepatitis C, D, and E remain a distant goal, advances in vaccine and
adjuvant technology, including immunization with DNA-based vaccines, hold promise
for the future.

Publication Types: 
    Review

PMID: 12064790 [PubMed - indexed for MEDLINE]

596: Clin Infect Dis. 2002 Jul 1;35(1):91-2. Epub 2002 Jun 5.

Use of liver function tests to predict the magnitude of an outbreak of hepatitis 
A.

Castrodale L, Beller M, Middaugh J, McCumber B, Mynes-Spink K, Bernth G.

Epidemic Intelligence Service, Division of Applied Public Health Training,
Epidemiology Program Office, Centers for Disease Control and Prevention, Atlanta,
GA, USA. louisa_castrodale@health.state.ak.us

The results of liver function tests allowed local and state public health
professionals in Alaska to accurately predict the magnitude of an outbreak of
hepatitis A.

PMID: 12060882 [PubMed - indexed for MEDLINE]

597: Int Microbiol. 2001 Dec;4(4):223-6.

Global market: shellfish imports as a source of reemerging food-borne hepatitis A
virus infections in Spain.

Romalde JL, Torrado I, Ribao C, Barja JL.

Departamento de Microbiología y Parasitología, Facultad de Biología, Universidad 
de Santiago de Compostela, Spain. mpromald@usc.es

A total of 16 mollusk imports from South America to Spain, including clam and
scallop species, were analyzed for hepatitis A virus (HAV), due to the great
concern about this type of food after an important hepatitis A outbreak in
eastern Spain in September 1999. In addition, clams from the stock that had
caused the outbreak were also tested. Of the 17 stocks, four were positive for
the presence of HAV RNA as demonstrated by RT-PCR and Southern hybridization.
Contradictory analyses confirmed the results of the primary tests in all cases.
The findings obtained in this work strongly support the role of mollusk imports
from endemic areas of HAV as an important vehicle of hepatitis A, and demonstrate
the imperative need for sanitary control measures to prevent future outbreaks of 
this disease.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12051566 [PubMed - indexed for MEDLINE]

598: Mem Inst Oswaldo Cruz. 2002 Apr;97(3):301-5.

Hepatitis a outbreak in a public school in Rio de Janeiro, Brazil.

Villar LM, Esteves da Costa Mdo C, de Paula VS, Gaspar AM.

Departamento de Virologia, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, RJ,
21045-900, Brasil. lvillar@ioc.fiocruz.br

From June 1 to July 1 1999, an outbreak involving 25 cases of hepatitis A
occurred in a public school in Rio de Janeiro, Brazil. Since these cases were
notified to the State Health Department, the National Reference Center for
Hepatitis Viruses (CNRHV) was required to investigate the extent of hepatitis A
virus (HAV) dissemination. Blood samples from all students were tested for IgM
and total anti-HAV antibodies using a commercial enzyme-linked immunoassay
(ELISA). At the same time, a questionnaire was completed in order to identify
possible risk factors for HAV infection. The environmental investigation showed
that there was no fecal contamination of the water supply. The epidemiological
investigation demonstrated that almost 50% of this population was susceptible to 
HAV infection and probably person-to-person transmission was the principal mode
of virus dissemination. In this situation, a massive vaccination campaign could
control the HAV infection.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12048555 [PubMed - indexed for MEDLINE]

599: J Travel Med. 2002 Mar-Apr;9(2):71-5.

Empiric immunization versus serologic screening: developing a cost-effective
strategy for the use of hepatitis A immunization in travelers.

Fishbain JT, Eckart RE, Harner KC, Hospenthal DR.

Department of Medicine, Tripler Army Medical Center, Honolulu, Hawaii, USA.

BACKGROUND: Older individuals and those born overseas are thought at increased
risk of prior exposure and thus have naturally acquired immunity to hepatitis A. 
Whether these individuals or other groups of international travelers should be
screened for acquired immunity or empirically immunized is not clear. Hepatitis A
serology and risk factor data was obtained prospectively in patients presenting
for hepatitis A immunization and used to develop a cost-effective strategy for
the use of serologic screening and empiric immunization in our traveler
population. METHOD: Candidates for hepatitis A immunization were routinely
screened for total hepatitis A serum antibody. Risk factor data including country
of birth, travel history, and history of jaundice was collected.
Cost-effectiveness was assessed by comparing the cost of serology to screen all
patients plus cost to immunize those found to be seronegative with, the cost of
empirically immunizing all patients. RESULTS: Analyses were conducted comparing
age, travel history, country of birth, and history of jaundice for significance
in predicting seropositivity in a group of 115 subjects. Country of birth was
statistically a significant predictor of positive results with 80.0% of
foreign-born patients positive for total antibody against hepatitis A compared
with 35.6% of patients born in the United States. Living outside of the United
States (defined as greater than 30 days) was also correlated with a higher
prevalence of hepatitis A positive serology. Age was not predictive for the group
as a whole. A lower prevalence (24.3%) was noted in the group of US born
individuals aged 30 to 60. Travel and prior history of jaundice failed to
demonstrate significance. CONCLUSIONS: Employing a simple cost-effectiveness
equation using cost of serological testing, cost of vaccine, and prevalence of
acquired immunity in the community, a strategy was developed. In our population
it was cost-effective to screen all foreign-born individuals and those who had
lived outside the United States.

Publication Types: 
    Comparative Study

PMID: 12044273 [PubMed - indexed for MEDLINE]

600: J Travel Med. 2002 Mar-Apr;9(2):66-70.

An open randomized study of inactivated hepatitis A vaccine administered
concomitantly with typhoid fever and yellow fever vaccines.

Jong EC, Kaplan KM, Eves KA, Taddeo CA, Lakkis HD, Kuter BJ.

University of Washington School of Medicine, Seattle, Washington, USA.

BACKGROUND: Concomitant administration of several vaccines is a common practice
when travel clinics prepare persons for international travel. The purpose of the 
study was to compare the immunogenicity and safety of hepatitis A, typhoid fever,
and yellow fever vaccines administered concomitantly with hepatitis A vaccine
administered alone and typhoid fever and yellow fever vaccines administered
alone. METHODS: Healthy adults 18 to 55 years of age were randomized to receive
either VAQTA, TyphimVi, and YF-VAX on day 0 and VAQTA at week 24 (Group 1);
TyphimVi and YF-VAX on day 0 and an optional dose of VAQTA 1 month later (Group
2); or VAQTA at day 0 and week 24 (Group 3). RESULTS: From March to December
1997, a total of 240 subjects were enrolled, 80 in each treatment group. Most
were female and Caucasian, and the mean age was 29.4 years. Four weeks after
vaccine dose 1, seroconversion to protective antibody levels against hepatitis A 
was 95.9% in Group 1 and 100% in Group 3. In Group 1, 93.4% of subjects
demonstrated at least a 4-fold rise in neutralizing antibody levels against
typhoid, compared with 90% in Group 2. Serum neutralizing antibody against yellow
fever developed in 98.6% of subjects in Group 1 compared with 100% in Group 2.
CONCLUSIONS: These findings were consistent with similarity in the immune
responses between treatment groups as defined a priori. The adverse experience
(AE) profile did not appear to be substantially affected by concomitant
administration of all three vaccines. Providing these three vaccines
concomitantly can simplify the process of obtaining pretravel prophylaxis and may
help ensure that all needed vaccines are administered.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 12044272 [PubMed - indexed for MEDLINE]

601: J Infect Dis. 2002 Jun 1;185(11):1668-71. Epub 2002 May 7.

Relative infectivity of hepatitis A virus by the oral and intravenous routes in 2
species of nonhuman primates.

Purcell RH, Wong DC, Shapiro M.

Hepatitis Viruses Section, Laboratory of Infectious Diseases, National Institute 
of Allergy and Infectious Diseases, National Institutes of Health, 50 South
Drive, Bethesda, MD 20892-8009, USA. rpurcell@niaid.nih.gov

Hepatitis A virus (HAV) is naturally transmitted by the fecal-oral route but can 
also be transmitted intravenously. To determine the relative infectivity of these
2 routes, an infectivity titration of a standard challenge pool of virulent HAV
was performed in tamarins and chimpanzees. In both species, 1 oral dose of HAV
was equivalent to 10(4.5) intravenous doses. These findings have relevance for
attempts to develop live, attenuated HAV vaccines that can be administered
orally.

Publication Types: 
    Research Support, U.S. Gov't, P.H.S.

PMID: 12023776 [PubMed - indexed for MEDLINE]

602: Infection. 2002 Apr;30(2):94-7.

Occupational risk for hepatitis A and hepatitis E among health care
professionals?

Nübling M, Hofmann F, Tiller FW.

Dept of Applied Physiology, Occupational Medicine and Infectiology, University of
Wuppertal, Germany. ffas.freiburg@t-online.de

BACKGROUND: Since transmission routes of hepatitis E virus (HEV) and hepatitis A 
virus (HAV) are believed to be similar, comparable risk factors and a correlation
between the two seroprevalence rates may be assumed. MATERIALS AND METHODS:
Anti-HAV and anti-HEV serology was assessed in 511 German subjects from nursing, 
pediatric nursing and administration groups, none of whom had been vaccinated
against HAV. At the same time a standardized questionnaire on occupational and
individual parameters was completed. RESULTS: Overall seroprevalence for anti-HEV
was 3.9%, for anti-HAV 28%. Multivariate analysis revealed that anti-HEV
seroprevalence was significantLy higher in persons working in emergency admission
or in surgery, while persons working in children's psychiatry were more likely to
be anti-HAV positive. Comparing the two serological resulLts, no contingency
difference was found (chi2 = 0.42 (df = 1), p > 0.05). CONCLUSION: Specific
departments of health care show higher prevalence of anti-HAV or anti-HEV. In the
case of HEV further studies in the exposed working field are needed. Since no
connection between the two serological results was found, transmission mechanisms
might be (partly) different.

PMID: 12018477 [PubMed - indexed for MEDLINE]

603: Vaccine. 2002 May 22;20(17-18):2243-8.

Adult infection with hepatitis A despite declining endemicity; in favor of adult 
vaccination.

Gillis D, Grotto I, Mimouni D, Huerta M, Gdalevich M, Shpilberg O.

Department of Pediatrics, Hadassah University Hospital, Ein-Kerem, Jerusalem,
Israel

Seropositivity against hepatitis A was examined among 4806 standing army
personnel (4497 males and 309 females) during 1998-1999. Each bi-annual birth
cohort examined showed a decline in seropositivity compared to the previous one. 
When compared with a study performed in 1989, however, for each of the 1961-1962,
1963-1964, 1965-1966, 1967-1968 and 1969-1970 birth cohorts examined, the
1998-1999 study showed 5-15% higher seropositivity. This trend remained after
controlling for differences between the two studies in ethnic origin, sibship
size and level of education. The overall seroconversion rate is estimated as
1.15% per year and the clinical to subclinical ratio as 1:14. Thus, hepatitis A
infection continues to occur in the young adult age group and vaccination of this
group should be considered.

PMID: 12009279 [PubMed - indexed for MEDLINE]

604: Int J Food Microbiol. 2002 May 5;75(1-2):11-8.

Detection of hepatitis A virus in mussels from different sources marketed in
Puglia region (South Italy).

Chironna M, Germinario C, De Medici D, Fiore A, Di Pasquale S, Quarto M, Barbuti 
S.

Department of Internal Medicine, University of Bari, Policlinico, Italy.

Hepatitis A virus (HAV) infection is endemic in Puglia (South Italy).
Epidemiological studies indicate that shellfish consumption, particularly
mussels, is a major risk factor for HAV infection, since these products are eaten
raw or slightly cooked. Nested reverse transcriptase-polymerase chain reaction
(RT-PCR) has been shown to be a sensitive technique for the detection of HAV in
mussels. The aim of the present study was to detect the presence of HAV in a
large sample of mussels by nested RT-PCR and to confirm the presence of
infectious viral particles in positive samples by cell culture infection and
RT-PCR confirmation. Two hundred and ninety samples of mussels from different
sources were collected between December 1999 and January 2000. One hundred
samples were collected before being subjected to depuration, 90 after depuration,
and 100 were sampled in different seafood markets. HAV-RNA was detected in 20
(20.0%) of non-depurated mussels, in 10 (11.1%) of depurated samples, and in 23
(23.0%) of samples collected in the shellfish markets, without any significant
difference in the prevalence of positive samples by collection sources (chi2 =
4.79, p = 0.09). Of the 53 samples found positive by nested RT-PCR, 18 (34.0%)
resulted positive by cell culture assay. No relationship between viral
contamination and bacterial contamination was found (p = 0.41). This study
confirms the usefulness of molecular techniques in detecting HAV in shellfish
and, thus, for the screening of a large sample of naturally contaminated mussels.
Improved shellfish depuration methods are needed to obtain virus-safe shellfish
and reduce the risk for public human health.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11999106 [PubMed - indexed for MEDLINE]

605: Hepatogastroenterology. 2002 Mar-Apr;49(44):524-8.

Acute hepatitis A virus infection: a review of prognostic factors from 25 years
experience in a tertiary referral center.

Kyrlagkitsis I, Cramp ME, Smith H, Portmann B, O'Grady J.

Institute of Liver Studies, King's College Hospital, London SE5 9RS, UK.
verdi@compulink.gr

BACKGROUND/AIMS: Hepatitis A is usually a mild, self-limiting illness but can
result in severe or fatal disease. We reviewed 25 years experience to determine
what factors predispose to severe or fatal disease. METHODOLOGY: We identified 97
patients admitted between 1974-1999 with acute hepatitis A. Clinical, biochemical
and histological data were correlated with outcome and patients were screened for
evidence of hepatitis B or C virus coinfection and coexisting autoimmunity.
RESULTS: Fifty-five patients had liver failure with hepatic encephalopathy of
whom 29 died and 6 underwent liver transplantation. Patients with liver failure
were significantly older than those without (mean age: 42.2 +/- 13.3 vs. 29.2 +/-
7.8, P = 0.0001), and liver failure patients who died were older than those
surviving (47.5 +/- 12.7 vs. 36.3 +/- 11.6, P = 0.0001). Hyperacute liver failure
predicted good outcome (P = 0.0001). Three patients with viral coinfection had
established cirrhosis and died. Detectable autoantibodies did not correlate with 
outcome or severity. Patients acquiring infection abroad were more likely to have
liver failure than those acquiring infection in the UK (P = 0.023). CONCLUSIONS: 
Age is the best predictor for outcome in patients with liver failure from
hepatitis A. Underlying chronic liver disease, and the time of onset of
encephalopathy are also factors affecting outcome. Infection acquired abroad has 
a worse prognosis.

PMID: 11995487 [PubMed - indexed for MEDLINE]

606: Pediatrics. 2002 May;109(5):839-45.

Hepatitis A virus infections in the United States: model-based estimates and
implications for childhood immunization.

Armstrong GL, Bell BP.

Epidemiology Branch, Division of Viral Hepatitis, National Center for Infectious 
Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia 30333,
USA. gca3@cdc.gov

OBJECTIVE: The high prevalence of antibody to hepatitis A virus (HAV) in the US
population suggests that the incidence of infection is much higher than reported,
but the infection rate is difficult to measure directly because of anicteric
infection and underreporting. We present a model that reconciles the reported
incidence of hepatitis A with the observed prevalence of antibody to HAV and
provides an estimate of the true incidence of HAV infection. METHODS: In the
model, reported incidence of hepatitis A in the United States was adjusted to
account first for anicteric infection and then for underreporting and declining
incidence over time such that the prevalence predicted by the model approximated 
that observed in 2 nationwide surveys. RESULTS: The model showed incidence in the
susceptible population declining by 4.5% per year. As incidence declined early in
the 1900s, the average age at infection increased, leading to a paradoxical
increase in the incidence of icteric infection followed by a slow decline. The
model estimated approximately 270 000 (range: 190 000-360 000) infections
annually from 1980 to 1999, 10.4 times the number of hepatitis A cases actually
reported during this period. More than half of these infections occurred in
children who were younger than 10 years, most of which would have been clinically
unrecognizable as hepatitis. CONCLUSIONS: These results suggest a large reservoir
of infection in children and that interruption of transmission in children may
substantially reduce incidence of hepatitis A overall.

PMID: 11986444 [PubMed - indexed for MEDLINE]

607: J Travel Med. 2002 Jan-Feb;9(1):10-6.

Comment in:
    J Travel Med. 2002 Jan-Feb;9(1):1-2.

Ineffectiveness of the current strategy to prevent hepatitis A in travelers.

De Serres G, Duval B, Shadmani R, Boulianne N, Pohani G, Naus M, Fradet MD,
Rochette L, Ward BJ, Kain KC.

Institut National de Santé Publique du Québec, Québec, Canada.

BACKGROUND: Each year, a large number of Canadians travel to regions of the world
where hepatitis A remains endemic. Many of these travelers are not immune and the
current preventive strategy relies wholly on self-referral to a travel clinic.
All of the costs associated with such a visit are assumed by the traveler. We
estimated the effectiveness of this strategy. METHODS: This case-control study
included 108 travel-related hepatitis A cases with onset of disease between 1997 
and 1999 and 620 controls who traveled during the same period. RESULTS: Hepatitis
A was strongly associated with high-risk travel (Odds Ratio = 7.2, 95% Confidence
Interval 1.76-29.4), but only 7% of cases were found in this category. The risk
of hepatitis A was 5 times lower in travelers who visited a travel clinic than in
those who did not (80% efficacy). However, only 14% of the controls visited a
travel clinic. As a result, the effectiveness of the current strategy is
estimated to be 11% (80% of 14%). CONCLUSIONS: Hepatitis A in travelers can be
prevented effectively by attendance at a travel clinic. Unfortunately, most
travelers do not visit such clinics prior to departure. Even if all high-risk
travelers were to visit a travel clinic and receive vaccination, this would have 
negligible impact on the number of travel-related hepatitis A cases
(approximately 7% reduction). The current strategy for the prevention of
hepatitis A in travelers is ineffective and should be reexamined.

PMID: 11962352 [PubMed - indexed for MEDLINE]

608: Exp Toxicol Pathol. 2002 Feb;53(6):413-20.

Experimental hepatitis A virus (HAV) infection in Callithrix jacchus: early
detection of HAV antigen and viral fate.

Pinto MA, Marchevsky RS, Baptista ML, de Lima MA, Pelajo-Machado M, Vitral CL,
Kubelka CF, Pissurno JW, Franca MS, Schatzmayr HG, Gaspar AM.

Department of Virology, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.

Common marmosets (Callithrixjacchus) were orally inoculated with a Brazilian
strain (HAF-203) of hepatitis A virus (HAy). Three monkeys were euthanized at
postinoculation hours 6, 12 and 24 to investigate the early events of HAV
infection. Following others three inoculated and one control marmosets remained
throughout the 46 day to evaluation of viral excretion. Different samples were
collected to detect sequential presence of HAV RNA by nested reverse
transcription-polymerase chain reaction (RT-PCR) in liver, saliva, bile and
stools at 6 hours to 461h days postinoculation. Liver tissues were examined by
immunofluorescence assay in a confocal laser-scanning microscope for the presence
of HAV antigen. HAV RNA was detected in saliva during the course of the study, in
bile from 24 hours to 46 days. in stools from 7 to 46 days and liver at 12 hours 
postinfection. In immunofluorescence of liver stained preparations, viral antigen
was present at six hours after inoculation throughout the remainder of the 46-day
study. The animals developed histological and biochemical acute hepatitis after
second week postinoculation. Spleen, duodenum, and mesenteric lymph nodes
specimens were negative for HAV antigens. This study supports the possibility
that in Callithrixjacchus orally inoculated with hepatitis A virus the saliva
route may be additional way of viral elimination. The viral replication in the
liver was responsible for biliary HAV presence and latter HAV detection in fecal 
samples.

PMID: 11930901 [PubMed - indexed for MEDLINE]

609: J Infect Dis. 2002 Apr 15;185(8):1170-3. Epub 2002 Mar 20.

Hepatitis A virus infection in tamarins: experimental transmission via
contaminated factor VIII concentrates.

Chudy M, Stahl-Hennig C, Berger A, Nübling CM, Hunsmann G, Rabenau HF, Löwer J.

Division of Virology, Paul-Ehrlich-Institut, Paul-Ehrlich-Strasse 51-59, 63225
Langen, Germany. chumi@pei.de

An experimental hepatitis A virus (HAV) transmission study was performed in 3
tamarins, using a factor VIII concentrate linked to a recent outbreak of HAV
infections in German hemophiliacs. The typical indicators for HAV infection were 
investigated in feces and serum samples. One tamarin showed a classical HAV
infection with seroconversion. HAV antigen and HAV RNA were detected in feces of 
a second animal, but no seroconversion was observed until 19 weeks after
inoculation. The HAV sequences from the reverse-transcription- and polymerase
chain reaction-positive samples of the 2 animals were identical to the deduced
HAV sequences of the chain of infection (from plasma pool to final product to
patients). The study results provide conclusive evidence of the presence of
infectious HAV in coagulation factor concentrate. Because a number of HAV
transmission episodes have been described for solely solvent/detergent-treated
factor VIII preparations, continued use of these agents seems questionable.

PMID: 11930328 [PubMed - indexed for MEDLINE]

610: Ann Trop Paediatr. 2002 Mar;22(1):59-61.

Acute infantile haemorrhagic oedema associated with hepatitis A.

Bozaykut A, Atay E, Atay Z, Ipek IO, Akin M, Dursun E.

Department of Pediatrics, Zeynep Kamil Hospital, Istanbul, Turkey.

Acute infantile haemorrhagic oedema (AIHO) is characterised by purpura,
ecchymosis and inflammatory oedema of the face and extremities. It is seen in
children aged 4-24 months. The atiology is not known. We report a case of AIHO
diagnosed by skin biopsy demonstrating leukocyte-elastic vasculitis. Laboratory
studies showed positive hepatitis A IgM and IgG antibodies. The liver function
tests were normal, indicating subclinical hepatitis. Cryoglobulinaemia was
detected, suggesting that the disease was related to hepatitis A.

Publication Types: 
    Case Reports

PMID: 11926052 [PubMed - indexed for MEDLINE]

611: Can J Public Health. 2002 Jan-Feb;93(1):52-3.

Erratum in:
    Can J Public Health 2002 May-Jun;93(3):232.

Seroprevalence and risk factors for hepatitis A among Montreal street youth.

Roy E, Haley N, Leclerc P, Cédras L, Bédard L, Allard R.

Montreal Regional Public Health Department, McGill University, Montreal, QC.
eroy@santepub-mtl.qc.ca

OBJECTIVE: To estimate the prevalence of hepatitis A virus (HAV) antibodies among
Montreal street youth. METHOD: Anti-HAV antibody testing was performed on blood
samples from a hepatitis B and C study conducted among street youth in 1995-96.
RESULTS: Among the 427 youth aged 14 to 25 years, prevalence of HAV antibodies
was 4.7% (95% confidence interval [CI]: 2.9%-7.2%). A multivariate logistic
regression analysis showed that birth in a country with a high anti-HAV
prevalence (Adjusted odds ratio [AOR]: 200.7; 95% CI: 38.1-1058.4), having had
sexual partner(s) with history of unspecified hepatitis (AOR: 13.8; 95% CI:
4.2-45.2), and insertive anal penetration (AOR: 5.1; 95% CI: 1.6-16.7) were
independently associated with infection. CONCLUSION: Based on the relatively low 
HAV prevalence, the high prevalence of risk factors for infection, and the
substantial hepatitis B and C prevalence, vaccination against hepatitis A is now 
actively promoted among Montreal street youth.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11925701 [PubMed - indexed for MEDLINE]

612: Am J Gastroenterol. 2002 Mar;97(3):721-8.

Comment in:
    Am J Gastroenterol. 2002 Nov;97(11):2924-5; author reply 2925.

The cost-effectiveness of hepatitis A vaccination in patients with chronic
hepatitis C viral infection in the United States.

Arguedas MR, Heudebert GR, Fallon MB, Stinnett AA.

Division of Gastroenterology and Hepatology, School of Public Health, University 
of Alabama at Birmingham, 35294-0007, USA.

OBJECTIVE: Hepatitis A vaccination is recommended for patients with chronic
hepatitis C. Our aim was to analyze the cost-effectiveness of hepatitis A
vaccination in these patients. The specific strategies evaluated were: no
vaccination, targeted vaccination, and universal vaccination. METHODS: Clinical
estimates were based on published data. Costs estimates were based on published
data and institutional Medicare reimbursement rates. Health-related
quality-of-life weights were derived from published data and expert estimates.
The target population consisted of patients 45 yr of age with chronic hepatitis C
followed every 6 months until death. We adopted a societal perspective. RESULTS: 
Compared with no vaccination, targeted vaccination was associated with an
incremental cost-effectiveness ratio of $51,000 per quality-adjusted life-year.
The incremental cost-effectiveness ratio of universal vaccination compared with
targeted vaccination was $3,900,000 per quality-adjusted life-year. The results
were particularly sensitive to the incidence of hepatitis A, probability of
fulminant hepatic failure, and costs of hepatitis A antibody screening and
vaccination. CONCLUSIONS: Targeted vaccination for hepatitis A in patients with
chronic hepatitis C may be a cost-effective strategy to decrease the morbidity
and mortality associated with hepatitis A superinfection. Universal vaccination
is not a cost-effective alternative to targeted vaccination in this target
population.

PMID: 11922569 [PubMed - indexed for MEDLINE]

613: Ren Fail. 2002 Jan;24(1):97-102.

Acute renal failure associated with nonfulminant hepatitis A virus infection.

Adaş M, Tanakol R, Yarman S, Boztepe H, Ecder T, Alagol F.

University of Istanbul, Istanbul Faculty of Medicine, Internal Medicine
Department, Endocrinology and Metabolism Division, Istanbul, Turkey.
mineadas@yahoo.com

Hepatitis A is usually a mild self-limiting infection of the liver. Nonfulminant 
acute renal failure very rarely complicates type A viral hepatitis. An unusual
case, a 32-year-old female with serologically proven acute hepatitis A infection,
was complicated by acute renal failure and the patient in this study is the first
case associated with Cushing's disease. She recovered, and the laboratory tests
returned normal one month after initial hospitalization. Although the mechanism
responsible for renal failure in acute hepatitis A virus infection is still
uncertain, possible causes are discussed with the review of literature.

Publication Types: 
    Case Reports

PMID: 11921703 [PubMed - indexed for MEDLINE]

614: J Gastroenterol Hepatol. 2001 Nov;16(11):1239-43.

Glucose-6-phosphate dehydrogenase deficiency is associated with increased initial
clinical severity of acute viral hepatitis A.

Gotsman I, Muszkat M.

Division of Medicine, Hadassah University Hospital, Jerusalem, Israel.
Igotsman@hadassah.org.il

BACKGROUND AND AIM: In glucose-6-phosphate dehydrogenase (G6PD) deficiency, the
enzyme is deficient in liver cells as well as in erythrocytes. It has been
suggested that this may be associated with a more severe clinical presentation of
acute viral hepatitis A. The aim of this study is to determine the severity of
liver disease in patients with viral hepatitis and G6PD deficiency. METHODS:
Eighteen patients with diagnosed G6PD deficiency and acute hepatitis A were
compared with 18 matched control patients with hepatitis A in a university
hospital for liver disease severity and clinical outcome. RESULTS: Two of 18
patients with G6PD deficiency had neurological deterioration. Patients with G6PD 
deficiency had a mean peak prothrombin time (PT) that was significantly prolonged
as compared with the control group (15.5 +/- 3.7 vs 12.9 +/- 2.0 s, respectively,
P < 0.02), and a significantly higher proportion had an abnormal PT (PT > 13.3
s): 61 versus 11% (P < 0.0001). Hemolysis occurred in 44% of the G6PD deficiency 
patients. Total and direct bilirubin were significantly higher in all patients
with G6PD deficiency, including patients without hemolysis. There was no
significant difference in liver enzyme levels between the two groups. Patients
with G6PD deficiency had a longer average hospital stay (9.5 +/- 4.8 vs 3.4 +/-
0.8 days, respectively, P < 0.001). There was no difference in the final clinical
outcome between the two groups, and recovery of liver function was seen in all
patients. CONCLUSIONS: Glucose-6-phosphate dehydrogenase deficiency in patients
with hepatitis A causes a more severe initial clinical presentation, but does not
alter the final clinical outcome.

PMID: 11903742 [PubMed - indexed for MEDLINE]

615: Euro Surveill. 2001 Oct;6(10):151-3.

Imported rocket salad partly responsible for increased incidence of hepatitis A
cases in Sweden, 2000-2001.

Nygård K, Andersson Y, Lindkvist P, Ancker C, Asteberg I, Dannetun E, Eitrem R,
Hellström L, Insulander M, Skedebrant L, Stenqvist K, Giesecke JG.

Smittskyddsinstitutet (Swedish Institute for Infectious Disease Control, SMI),
Stockholm, Sweden.

An increased incidence of domestic hepatitis A without any obvious source of
infection in Sweden and a small outbreak in late spring 2001 led to the
undertaking of a case-control study. Consumption of imported rocket salad was
clearly associated with disease (odds ratio 9.1, 95% confidence interval 1.5 to
69). The importation of vegetables from countries where hepatitis A is endemic to
countries where this disease is not endemic continues to be a public health
problem.

PMID: 11891384 [PubMed - indexed for MEDLINE]

616: J Viral Hepat. 2002 Mar;9(2):101-6.

Quantification and duration of viraemia during hepatitis A infection as
determined by real-time RT-PCR.

Costa-Mattioli M, Monpoeho S, Nicand E, Aleman MH, Billaudel S, Ferré V.

Laboratoire de Virologie, Institut de Biologie, CHU Nantes, Nantes 44093, France.

Human transmission studies and molecular techniques have provided evidence that
transient viraemia occurs during infection with hepatitis A virus (HAV). However,
the duration of its presence and levels during the phases of clinical disease and
convalescence has not yet been well studied in human patients. Real-time RT-PCR
techniques are increasingly used to quantify RNA viruses for diagnosis and/or
research purposes. We have optimized a one-step RT-PCR that contains a
dual-labelled fluorogenic probe to quantify the 5' noncoding region (5' NCR) of
HAV. This method has a dynamic range (5-5 x 10(6) copies). The coefficient of
regression of the standard curve was, on average 0.978. Intra-assay CVs% varied
from 6.1% to 0.98%, and interassay CVs% from 6.46% to 2.1%. In the currently
reported study 41 HAV IgM positive serum samples and 200 serum samples from
healthy blood donors were tested by the quantitative RT-PCR method. The mean
values on the first day of diagnosis found was 6.38 x 10(5) copies/mL. In a
longitudinal study, viraemia persisted for an average of 60 days after clinical
onset. These results show that viraemia in HAV infection lasts for many weeks.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11876791 [PubMed - indexed for MEDLINE]

617: Am J Gastroenterol. 2002 Feb;97(2):427-34.

The cost-effectiveness of vaccinating chronic hepatitis C patients against
hepatitis A.

Jacobs RJ, Koff RS, Meyerhoff AS.

Capitol Outcomes Research, Alexandria, Virginia 22310, USA.

OBJECTIVES: Although hepatitis A vaccination is recommended for persons with
chronic liver disease, the cost-effectiveness of vaccinating patients with
chronic hepatitis C virus has not been extensively studied. We evaluated its
costs and benefits. METHODS: A Markov model was used to assess cost-effectiveness
from the health system and societal perspectives. Costs of hepatitis A screening 
and vaccination were compared with savings from reduced hepatitis A treatment and
work loss to determine net costs of a "screen and vaccinate" strategy. Net costs 
were compared with longevity gains to assess cost-effectiveness. RESULTS: Based
on hypothetical cohorts of 100,000 patients, vaccination would reduce the number 
of hepatitis A cases 63-72%, depending on patient age. Screening and vaccination 
costs of $5.2 million would be partially offset by $1.5-$2.8 million reductions
in hepatitis A treatment costs and $0.2-$1.0 million reductions in work loss
costs. From the health system perspective, vaccination would cost $22,256,
$50,391, and $102,064 per life-year saved for patients vaccinated at ages 30, 45,
and 60 yr, respectively. Cost-effectiveness ratios improve when work loss
prevention is considered. Results are most sensitive to hepatitis A infection and
hospitalization rates, and the rate used to discount future benefits to their
present values. CONCLUSIONS: Hepatitis A vaccination of chronic hepatitis C
patients would substantially reduce morbidity and mortality in all age groups
examined. Consistent with other medical interventions for chronic hepatitis C
patients, cost-effectiveness is most favorable for younger patients.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11866283 [PubMed - indexed for MEDLINE]

618: Clin Nephrol. 2002 Feb;57(2):149-53.

Interstitial nephritis, acute renal failure in a patient with non-fulminant
hepatitis A infection.

Vaboe AL, Leh S, Forslund T.

Renal Research Group, Institute of Medicine, Haukeland University Hospital,
Bergen, Norway. alva@haukeland.no

This is the first report from Norway of a patient with interstitial nephritis and
renal failure due to non-fulminant hepatitis A virus (HAV) infection. HAV
infection was confirmed by positive anti-HAV IgM serology. All tests for other
virus infections were negative. At admittance serum creatinine (s-Creat) and
blood urea nitrogen (BUN) concentration were 539 microlmol/l and 32.6 mmol/l
increasing the following days to 890 micromol/l and 39.9 mmol/l, respectively.
Nine courses of hemodialysis had to be given. Kidney biopsy specimen showed
interstitial edema, lymphocytic cell infiltration and acute tubular injury with
normal glomeruli. Examination with immunohistochemistry was negative. In contrast
to the findings associated with HBV and HCV infection in which glomerular disease
is predominantly found, the HAV infection in our patient was associated with
interstitial nephritis and acute tubular necrosis. The prognosis of the renal
failure due to HAV infection was good although the recovery was substantially
delayed.

Publication Types: 
    Case Reports

PMID: 11863126 [PubMed - indexed for MEDLINE]

619: Eur J Epidemiol. 2001;17(5):429-35.

Prevalence of markers for hepatitis A, B and C in the German population. Results 
of the German National Health Interview and Examination Survey 1998.

Thierfelder W, Hellenbrand W, Meisel H, Schreier E, Dortschy R.

Robert Koch-Institut, Berlin, Germany. w.thierfelder@rki.de

The prevalence of serological parameters indicative of infection with hepatitis
A, B and C was determined using sera collected from representative population
samples in the former East German (new) federal states and the West German (old) 
federal states during the German National Health and Examination Survey in 1998. 
Sera were tested for antibodies to hepatitis A virus (HAV), to hepatitis B core
antigen (HBc) and to hepatitis B surface antigen (HBsAg), hepatitis C Virus
(HCV), as well as for the presence of HBsAg and HCV-RNA. The mean weighted
prevalence of anti-HAV was 46.5% (95% CI: 45.3-47.7) and increased markedly with 
age. The mean weighted prevalence of past infection with hepatitis B was 7.7%
(95% CI: 7.0-8.4) in the old federal states and 4.3% (95% CI: 3.2-5.3) in the new
federal states, corresponding to an overall prevalence of 7.0% (95% CI: 6.4-7.6).
The mean weighted prevalence of HBsAg carriage was 0.6% (95% CI: 0.4-0.8), while 
the prevalence of HCV antibodies was 0.4% (95% CI: 0.2-0.5).

PMID: 11855576 [PubMed - indexed for MEDLINE]

620: J Occup Environ Med. 2002 Feb;44(2):109-15.

Cost-utility analysis of hepatitis A prevention among health-care workers in
Israel.

Chodick G, Lerman Y, Wood F, Aloni H, Peled T, Ashkenazi S.

Sackler Faculty of Medicine, Tel Aviv University, Department of Epidemiology &
Preventive Medicine, POB 39040 Ramat-Aviv, Tel Aviv 69978, Israel.
gabbychodick@hotmail.com

This study was conducted to evaluate the efficiency of different strategies of
preventing hepatitis A (HA) among physicians, nurses, and paramedical staff by
means of cost-effectiveness analysis. The strategies compared were passive
immunization during a hepatitis A outbreak, systematic mass vaccination of all
workers, and screening for antibodies to HA virus followed by vaccination of
nonimmune employees. To predict the prevented number of HA cases, an
epidemiological model was incorporated based on our previous nationwide study on 
clinical HA cases, seroepidemiological survey, and other scientific medical
literature. Under the model assumptions, the lowest cost per prevented HA case
($6240) was achieved by screening prior vaccination among 18- to 39-year-old
physicians and paramedical workers, and highest ($61,858) by mass vaccination of 
nurses over age 39 years. Because the price per prevented case may show that mass
vaccination is highly cost-effective, especially among 18- to 39-year-old
physicians and paramedical workers ($6399 and $8196, respectively), the cost per 
gained quality-adjusted life-year seems less attractive ($56,532 and $61,350,
respectively). This cost per saved quality-adjusted life-year is similar to many 
other medical interventions but is markedly higher than other primary prevention 
vaccines, which are mostly associated with a negative ratio. In view of the
conducted study, and taking $60,000 as a limit cost per saved quality-adjusted
life-year, we propose selective vaccination for physicians and for paramedical
workers. Mass vaccination should be offered to all health care workers, aside
from nurses 40+ years of age, once the active HA vaccine price is reduced to $23.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11851212 [PubMed - indexed for MEDLINE]

621: Arch Med Res. 2002 Jan-Feb;33(1):67-73.

A two-dose combined vaccine against hepatitis A and hepatitis B in healthy
children and adolescents compared to the corresponding monovalent vaccines.

Ramonet M, da Silveira TR, Lisker-Melman M, Rüttimann R, Pernambuco E, Cervantes 
Y, Cañero-Velasco MC, Falleiros-Carvalho LE, Azevedo T, Targa-Ferreira C, Clemens
SA.

Unidad de Gastroenterología Pediátrica, Hospital Nacional Alejandro Posadas
Haedo, Buenos Aires, Argentina.

BACKGROUND: Immunization against hepatitis A and B has been available for some
time, protecting against both infections. With a view to achieving further
reduction in the number of interventions and increasing convenience of the
vaccinee, we investigated the reactogenicity and immunogenicity of a combined
hepatitis A and B vaccine in healthy 4- to 20-year-old subjects at a 0, 6-month
schedule. METHODS: Two hundred forty-eight study subjects were allocated to two
study groups and received either two doses of the combined hepatitis A and B
vaccine (68% of subjects) or the corresponding monovalent hepatitis A and
hepatitis B vaccines (32% of subjects) concomitantly in opposite arms.
Reactogenicity was assessed via diary cards after each vaccination. Serum samples
were analyzed at months 1, 2, 6, and 7. RESULTS: All vaccines were well tolerated
and very few symptoms were scored as severe. All but one subject seroconverted
for anti-hepatitis A virus (anti-HAV) antibodies (98.6%) and 100% of subjects
seroconverted for anti-hepatitis B (HBs) antibodies, with respective
seroprotection rates of 98.7% for the combined vaccine group and 95.9% for the
concomitant vaccine group (p >0.05), respectively. Geometric mean titers were
higher in the group receiving the combined vaccine: 6,635 mIU/mL vs. 2,728 mIU/mL
(p = 0.0001) for anti-HAV and 3,362 mIU/mL vs. 1,724 mIU/mL (p = 0.0205) for
anti-HBs, respectively. Younger subjects had a stronger immune response compared 
to older subjects. CONCLUSIONS: The combined hepatitis A and B vaccine was well
tolerated at this two-dose schedule. The combined vaccine had higher
immunogenicity, probably explained by a adjuvant effect of the antigens.
Vaccination programs requiring fewer injections will most likely have a positive 
impact on compliance rate and comfort of the vaccinee.

Publication Types: 
    Clinical Trial
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 11825634 [PubMed - indexed for MEDLINE]

622: Aust N Z J Public Health. 2001 Dec;25(6):525-8.

Recognising and responding to outbreaks of hepatitis A associated with child
day-care centres.

Hanna JN, Humphreys JL, Hills SL, Richards AR, Brookes DL.

Tropical Public Health Unit, Queensland Health, Cairns.
jeffrey_hanna@health.qld.gov.au

OBJECTIVES: To assess the appropriateness of a protocol for recognising and
responding to outbreaks of hepatitis A in child day-care centres and to determine
if measles-mumps-rubella (MMR) vaccine was given too soon following the
administration of normal human immunoglobulin (NIGH) to young children to control
the outbreaks. DESIGN: Prospective surveillance to recognise cases of hepatitis A
associated with, and outbreaks of hepatitis A in, day-care centres. MAIN OUTCOME 
MEASURES: The percentage of initial ('sentinel') cases of hepatitis A associated 
with day-care centres that were subsequently recognised as also being 'index'
cases of outbreaks of hepatitis A in the centres, and the number of children 9-13
months of age when given NIGH who were subsequently given MMR less than three
months later. RESULTS: Only 18 (16%) of the 114 sentinel day-care associated
cases of hepatitis A were also index cases of outbreaks of hepatitis A in their
respective centres. A total of 105 cases of hepatitis A were associated with the 
18 outbreak centres; NIGH was administered to 928 (78%) of the attendee children,
and to 105 (82%) of the susceptible staff, at the 18 centres. Three of the five
children 9-13 months of age when given NIGH were given MMR less that three months
later. CONCLUSIONS: Although outbreaks of hepatitis A were common events in
day-care centres in north Queensland during the two-year study period, a single
case of hepatitis A associated with a centre was a poor predictor of an outbreak 
within that centre. Precautions must be taken to ensure that live vaccines are
not administered to young children too soon after NIGH.

PMID: 11824988 [PubMed - indexed for MEDLINE]

623: Pharmacoeconomics. 2002;20(1):1-7.

Economic evaluation of vaccination programmes: a consensus statement focusing on 
viral hepatitis.

Beutels P, Edmunds WJ, Antoñanzas F, De Wit GA, Evans D, Feilden R, Fendrick AM, 
Ginsberg GM, Glick HA, Mast E, Péchevis M, Van Doorslaer EK, van Hout BA; Viral
Hepatitis Prevention Board.

Viral Hepatitis Prevention Board, Antwerp, Belgium. philippe.beutels@ua.ac.be

The methods that have been used to estimate the clinical and economic impact of
vaccination programmes are not always uniform, which makes it difficult to
compare results between economic analyses. Furthermore, the relative efficiency
of vaccination programmes can be sensitive to some of the more controversial
aspects covered by general guidelines for the economic evaluation of healthcare
programmes, such as discounting of health gains and the treatment of future
unrelated costs. In view of this, we interpret some aspects of these guidelines
with respect to vaccination and offer recommendations for future analyses. These 
recommendations include more transparency and validation, more careful choice of 
models (tailored to the infection and the target groups), more extensive
sensitivity analyses, and for all economic evaluations (also nonvaccine related) 
to be in better accordance with general guidelines. We use these recommendations 
to interpret the evidence provided by economic evaluation applied to viral
hepatitis vaccination. We conclude that universal hepatitis B vaccination (of
neonates, infants or adolescents) seems to be the most optimal strategy
worldwide, except in the few areas of very low endemicity, where the evidence to 
enable a choice between selective and universal vaccination remains inconclusive.
While targeted hepatitis A vaccination seems economically unattractive, universal
hepatitis A vaccination strategies have not yet been sufficiently investigated to
draw general conclusions.

Publication Types: 
    Consensus Development Conference
    Review

PMID: 11817988 [PubMed - indexed for MEDLINE]

624: Epidemiol Infect. 2001 Dec;127(3):469-73.

An outbreak of hepatitis A amongst injecting drug users.

O'Donovan D, Cooke RP, Joce R, Eastbury A, Waite J, Stene-Johansen K.

Department of Public Health Medicine, East Sussex, Brighton Hove Health
Authority, Lewes.

This descriptive study investigated an outbreak of hepatitis A virus (HAV)
infection among injecting drug users (IDUs) and their contacts. Twenty-seven
cases of acute HAV infection were identified in a 5-month period. Connections
with the local injecting drug using (IDU) population were established for 25 of
the cases of whom 14 admitted to injecting drug use. HAV RNA genotyping revealed 
two HAV variants, closely related to variants found in Scandinavian IDUs and in
South East Asia. The study demonstrates that once HAV enters the IDU population
extensive outbreaks are possible. We recommend that all IDUs should be tested for
HAV and hepatitis B virus (HBV) infections and offered combined hepatitis A and B
vaccines if non-immune.

PMID: 11811880 [PubMed - indexed for MEDLINE]

625: Epidemiol Infect. 2001 Dec;127(3):461-7.

Immunization strategies to control a community-wide hepatitis A epidemic.

Thorburn KM, Bohorques R, Stepak P, Smith LL, Jobb C, Smith JP.

Spokane Regional Health District, WA 99201, USA.

One fifth of 527 cases of hepatitis A occurred in self-identified injection drug 
users during a community-wide epidemic in Spokane County (Washington) in 1997-8. 
We hypothesized that an immunization campaign targeted at illicit drug users
could control the epidemic. Starting in May 1998, hepatitis A vaccine was
provided to individuals in jails and other sites frequented by illicit drug
users. Volunteers at vaccination sites were surveyed about risk. Serial
convenience samples of jail inmates who denied previous vaccination were
anonymously tested for hepatitis A virus (HAV) immunoglobulin G (IgG). From May
to December 1998, 2765 high-risk individuals were vaccinated against hepatitis A.
The proportion of HAV IgG seropositive inmates increased from 30% to more than
50%. Our findings suggest that vaccination along with naturally occurring
infection increased the rate of hepatitis A immunity among illicit drug users
during the final months of the epidemic. This supports the hypothesis that
targeted immunization of high risk groups may shorten the natural history of a
community-wide epidemic.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11811879 [PubMed - indexed for MEDLINE]

626: J Med Assoc Thai. 2001 Oct;84(10):1477-80.

Seroprevalence of hepatitis A virus antibody among children and young adults in
Bangkok.

Pancharoen C, Mekmullica J, Kasempimolporn S, Thisyakorn U, Wilde H.

Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok,
Thailand.

OBJECTIVE: To determine the prevalence of hepatitis A virus (HAV) antibodies in
various age groups of healthy children and young adults who have not received the
hepatitis A vaccine. METHOD: Blood samples were collected from 825 volunteers
aged 1-30 years from a well baby clinic and five academic institutions in the Don
Mueang area from 1998 to 1999. Serum samples were assayed for specific HAV IgG
antibodies using a commercial enzyme-linked immunosorbent assay (ELISA) kit.
RESULTS: The seropositivity rate (12.4% overall) in each age group was as
follows: 1-3 years, 7.7 per cent; 4-7 years, 6.6 per cent; 8-11 years, 12.4 per
cent; 12-15 years, 10.7 per cent and 16-30 years, 25.9 per cent. CONCLUSIONS: In 
the Don Mueang area of Bangkok, the majority of children (< 16 years) do not have
natural immunity against HAV. The use of hepatitis A vaccine for this population 
should be considered. Pre-vaccination serologic screening for HAV IgG in children
may not be worthwhile.

PMID: 11804259 [PubMed - indexed for MEDLINE]

627: Vaccine. 2002 Jan 15;20(7-8):1157-62.

A new accelerated vaccination schedule for rapid protection against hepatitis A
and B.

Nothdurft HD, Dietrich M, Zuckerman JN, Knobloch J, Kern P, Vollmar J, Sänger R.

Department of Infectious Diseases and Tropical Medicine,
Ludwig-Maximilians-Universitaet Muenchen, Leopoldstrasse 5, 80802, Munich,
Germany. nothdurft@lrz.uni-muenchen.de

BACKGROUND: Increasing travel stresses the requirement for rapid protection
against infections such as hepatitis A and B. METHODS: This randomised,
multicentre study investigated an accelerated vaccination schedule using a
combined hepatitis A and B vaccine (Twinrix, Smithkline Beecham Biologicals)
compared with simultaneous administration of the two corresponding monovalent
vaccines. The combined vaccine was administered on days 0, 7 and 21, whereas the 
comparison group received hepatitis A vaccine on day 0 and hepatitis B vaccine on
days 0, 7 and 21. All subjects received booster vaccination at month 12. RESULTS:
At month 1, 100% of subjects in the combined group and 99% of the controls were
seropositive for anti-HAV antibodies. The corresponding seroprotection rates for 
anti-HBs antibodies were 82.0 and 83.9%, respectively. Examination of the 95%
confidence intervals (CIs) for the treatment differences showed the two vaccines 
to be equivalent in terms of immunogenicity 1 week after the initial vaccination 
course. Just prior to the booster, the seropositivity rate for anti-HAV was 96.2%
in the combined group and 95% in the control group. For anti-HBs, this was 94 and
91.6%, respectively. All subjects were seropositive for anti-HAV and
seroprotected against hepatitis B at month 13. The anti-HAV GMCs were 9571mIU/ml 
with the combined vaccine and 5206mIU/ml in control subjects. The anti-HBs titre 
was 26002 and 29,196mIU/ml, respectively. Both groups had a similar
reactogenicity profile. CONCLUSIONS: The accelerated schedule of the combined
vaccine provides a good immune response against hepatitis A and B antigens and is
suitable for last minute immunisation.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial

PMID: 11803077 [PubMed - indexed for MEDLINE]

628: Pediatr Hematol Oncol. 2002 Jan-Feb;19(1):67-70.

Thrombocytopenia and emperipolesis in a patient with hepatitis a infection.

Avci Z, Turul T, Catal F, Olgar S, Baykan A, Tekfam O, Gürgey A.

Hacettepe University School of Medicine, Department of Pediatrics, Ankara,
Turkey. zavcias@yahoo.com

lmmune thrombocytopenia is a benign, self-limiting disease in children,
responding well to treatment and generally associated with viral infections. A
13-year-old girl was admitted to a hospital with the epistaxis and purpura after 
an attack of jaundice 6 weeks before. The diagnosis of hepatitis A virus
(HAV)-induced thrombocytopenia was made. Furthermore, erythrophagocytosis by
megakaryocytes was demonstrated in the bone marrow of the patient. Although
hematologic complications following hepatitis B and C viruses are commonly
reported, the association of hepatitis A virus and thrombocytopenia has rarely
been described.

Publication Types: 
    Case Reports

PMID: 11787869 [PubMed - indexed for MEDLINE]

629: Clin Infect Dis. 2002 Feb 1;34(3):379-85. Epub 2001 Dec 14.

Influence of human immunodeficiency virus type 1 infection on acute hepatitis A
virus infection.

Ida S, Tachikawa N, Nakajima A, Daikoku M, Yano M, Kikuchi Y, Yasuoka A, Kimura
S, Oka S.

AIDS Clinical Center, International Medical Center of Japan, Tokyo 162-8655,
Japan.

To assess the possible influence of human immunodeficiency virus type 1 (HIV-1)
infection on the clinical course of acute hepatitis A virus (HAV) infection, 15
HIV-1-infected homosexual men and 15 non-HIV-infected age-matched subjects were
compared. HAV load was higher in HIV-1-infected than in non-HIV-infected patients
(P<.001). Duration of viremia in HIV-1-infected patients (median, 53 days) was
significantly (P<.05) longer than in non-HIV-infected patients (median, 22 days).
HIV-1-infected patients had lower elevations in alanine aminotransferase levels
than did non-HIV-infected patients (P<.01) but had higher elevations in alkaline 
phosphatase levels than did non-HIV-infected patients (P<.001). Some
HIV-1-infected patients still had HAV viremia when clinical symptoms had
disappeared and alanine aminotransferase levels had returned to normal (60-90
days after the onset of symptoms). HIV-1 infection was associated with
prolongation of HAV viremia, which might cause a long-lasting outbreak of HAV
infection in HIV-1-infected homosexual men.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11774086 [PubMed - indexed for MEDLINE]

630: Int Arch Occup Environ Health. 2001 Oct;74(8):589-93.

Task profile and risk of occupational hepatitis A infection in sewerage workers.

Nuebling M, Hofmann F.

Department of Applied Physiology, Occupational Medicine and Infectiology,
University of Wuppertal, Germany. ffas.frieburg@t-online.de

OBJECTIVE: The aim of the study was to assess to what extent parameters of
task-related occupational exposure influence anti-hepatitis A virus (anti-HAV)
seroprevalence in sewerage workers, using a new instrument for classification of 
exposure. METHODS: A new instrument for the assessment of work-related infection 
hazards was developed based on expert interviews, evaluation of literature and
theoretical considerations. It was included in a questionnaire for collecting
detailed information on occupational exposure, safety awareness, safety behaviour
and socio-demography. Anti-HAV status was assessed for all (n = 343)
(non-vaccinated) study participants. RESULTS: Marked differences in task profile 
and task-related exposure within the group of sewerage workers were found,
underlining the necessity of a detailed exposure analysis. In a multivariate
model three risk factors that were related significantly to anti-HAV positivity
were identified: age, country of origin and task-related exposure. CONCLUSIONS:
Since task profiles and occupational exposure differ strongly within the job
category of sewerage workers. evaluation of endangerment has to reflect
individual task-related exposure. The task-exposure matrix developed and
presented in this study is a practicable and valid instrument for exposure
assessment and may be used for the exposure analysis of further biological agents
in this working environment. Besides the known risk parameters age and origin,
our study demonstrates a dose-response relationship between the degree of
occupational exposure and the anti-HAV seroprevalence. Therefore, an effective
worksite HAV-prevention programme should consider all technical, structural and
educational measures that help to reduce individual exposure.

PMID: 11768049 [PubMed - indexed for MEDLINE]

631: JAMA. 2001 Dec 19;286(23):2968-73.

Control of hepatitis A through routine vaccination of children.

Averhoff F, Shapiro CN, Bell BP, Hyams I, Burd L, Deladisma A, Simard EP, Nalin
D, Kuter B, Ward C, Lundberg M, Smith N, Margolis HS.

National Immunization Program, Centers for Disease Control and Prevention,
Atlanta, GA, USA.

CONTEXT: The impact of routine hepatitis A vaccination of children living in
large communities with elevated disease rates has not been evaluated. OBJECTIVE: 
To determine the effect of routine vaccination of children on disease incidence
in a community with recurrent hepatitis A epidemics. DESIGN, SETTING, AND
PARTICIPANTS: Community-based demonstration project conducted from January 12,
1995, through December 31, 2000, in Butte County, California, among children aged
2 to 17 years. INTERVENTION: In 1995, vaccination was offered to children aged 2 
to 12 years during vaccination clinics conducted on 2 occasions 6 to 12 months
apart at most schools in the county. In 1996-2000, vaccine was distributed to
community health care clinicians, who vaccinated eligible children without
charge. Vaccine was also available at health department clinics, selected child
care centers, and other sites. MAIN OUTCOME MEASURES: Hepatitis A vaccination
coverage, hepatitis A incidence, and vaccine effectiveness. RESULTS: During the
study period, 29 789 (66.2%) of an estimated 44 982 eligible children received at
least 1 vaccine dose; 17 681 (39.3%) received a second dose. The number of
hepatitis A cases among the entire county population declined 93.5% during the
study period, from 57 cases in 1995 to 4 in 2000, the lowest number of cases
reported in the county since hepatitis A surveillance began in 1966. The 2000
incidence rate of 1.9 per 100 000 population was the lowest of any county in the 
state. Of the 245 cases reported during the 6-year period, 40 (16.3%) occurred
among children 17 years of age or younger, of which 16 (40%) occurred in 1995 and
only 1 in 2000. One of the 27 case patients eligible for vaccination had been
vaccinated, having received the first dose 3 days before symptom onset. The
estimated protective vaccine efficacy was 98% (95% confidence interval,
86%-100%). CONCLUSIONS: In this population, hepatitis A vaccine was highly
effective in preventing disease among recipients. Childhood vaccination appears
to have decreased hepatitis A incidence among children and adults and controlled 
the disease in a community with recurrent epidemics.

Publication Types: 
    Research Support, U.S. Gov't, P.H.S.

PMID: 11743837 [PubMed - indexed for MEDLINE]

632: J Med Virol. 2002 Jan;66(1):22-7.

Characterization of hepatitis A virus isolates from subgenotypes IA and IB in Rio
de Janeiro, Brazil.

de Paula VS, Baptista ML, Lampe E, Niel C, Gaspar AM.

Department of Virology, Oswaldo Cruz Institute, Rio de Janeiro, Brazil.

Hepatitis A virus (HAV) isolates from around the world have been classified into 
seven genotypes (I-VII). Most human strains belong to genotype I, which has been 
divided into two subgenotypes, A and B. South America has provided a small number
of strains studied at the genome level. In the present study, IgM anti-HAV
antibodies were detected in 116 out of 250 (46%) serum samples collected from
consecutive patients with acute hepatitis referred to the Brazilian Reference
Center for Viral Hepatitis, Rio de Janeiro. Viral RNA were extracted from all 250
samples and submitted to a reverse transcription-polymerase chain reaction
(RT-PCR) assay designed to amplify a genome segment in the VP1/2A junction
region. HAV RNA was detected in 54/116 (47%) and 17/134 (13%) IgM
anti-HAV-positive and -negative sera, respectively. In addition, HAV RNA was
detected in 17/35 (49%) IgM anti-HAV-positive sera that had been collected at a
day care center where cases of acute hepatitis were being observed for 3 months. 
Nucleotide sequences (168 bp) of PCR products were determined for 30 HAV
isolates. Phylogenetic analysis showed that 21 belonged to subgenotype IB, while 
9 were of subgenotype IA. Interestingly, a concomitant circulation of isolates
from subgenotypes IA and IB was observed in the day care center. Copyright 2002
Wiley-Liss, Inc.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11748654 [PubMed - indexed for MEDLINE]

633: Pediatr Infect Dis J. 2001 Aug;20(8):809-11.

Autoimmune complications associated with hepatitis A virus infection in children.

Ertem D, Acar Y, Pehlivanoglu E.

Division of Pediatric Gastroenterology and Nutrition, Marmara University School
of Medicine, Istanbul, Turkey.

Hepatitis A virus infection is usually a self-limited disease during childhood.
Autoimmune manifestations are rarely reported among patients. We describe two
children with acute hepatitis A infection who developed immune thrombocytopenia
and hepatic venous thrombosis during the course of acute infection.
Antiphospholipid antibodies were increased in both of them during the
thrombocytopenic and thrombotic complications and decreased during the resolution
of these events.

Publication Types: 
    Case Reports

PMID: 11734749 [PubMed - indexed for MEDLINE]

634: Pediatr Infect Dis J. 2001 Aug;20(8):805-7.

Hepatitis A vaccine in pediatric patients affected by metabolic liver diseases.

Giacchino R, Timitilli A, Castellano E, Di Rocco M, Fiore P, Soncini R, Romanò L.

Infectious Diseases Unit, Giannina Gaslini Children's Hospital, Genoa Italy.
raffaellagiacchino@ospedale-gaslini.ge.it

Twenty children with a variety of metabolic liver diseases were given two doses
of hepatitis A vaccine. Adverse reactions were mild. All subjects responded to
vaccine with seroconversion to hepatitis A virus antibodies after the first dose,
regardless of transaminase values, and had a booster effect from the second
doses.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11734747 [PubMed - indexed for MEDLINE]

635: Commun Dis Public Health. 2001 Sep;4(3):213-27.

Guidelines for the control of hepatitis A virus infection.

Crowcroft NS, Walsh B, Davison KL, Gungabissoon U; PHLS Advisory Committee on
Vaccination and Immunisation.

Immunisation Division, PHLS Communicable Disease Surveillance Centre, 61
Colindale Avenue, London NW9 5EQ. ncrowcroft@phls.org.uk

The PHLS Advisory Committee on Vaccination and Immunisation, following a review
of the evidence on control measures for preventing hepatitis A virus (HAV)
infection and widespread consultation, has prepared the following guidelines.
They include a description of the current epidemiology of HAV infection in
England and Wales, where most individuals are now susceptible to HAV. HAV
infection is uncommon, with around 1000 infections notified per year in England
and Wales. Clusters occur in families and in settings where potential for
faecal/oral spread is high, e.g. day care centres, nurseries, primary schools.
Larger outbreaks have been recorded in men who have sex with men and injecting
drug users. Personal hygiene remains the cornerstone of measures for preventing
HAV infection and its spread. Those with haemophilia, hepatitis B or C virus
infection or liver cirrhosis, intravenous drug users and men who have sex with
men should be offered HAV vaccination as a preventive measure. HAV vaccine should
be used for preventing secondary cases and outbreaks provided that patients are
informed that the latest date the vaccine is most likely to be effective in
preventing disease in contacts is probably 7 days from onset of illness in the
primary case. Human normal immunoglobulin (HNIG) should be offered in addition or
in preference to vaccine for contacts who are more than 7 days from onset of
illness in the primary case, and for those at risk of adverse outcome of HAV
infection. Individuals at particular risk of an adverse outcome to infection
include those more than 50 years old, with liver cirrhosis of any cause, or with 
pre-existing hepatitis B or C virus infection. HAV vaccine should be used to
prevent infection for travellers to countries where HAV infection is a risk. HNIG
is no longer indicated for travellers. Children travelling to such countries
should be offered vaccine from 5 years and consideration should be given to
vaccinating those aged 1-4 years.

Publication Types: 
    Guideline

PMID: 11732363 [PubMed - indexed for MEDLINE]

636: Commun Dis Public Health. 2001 Sep;4(3):163-70.

An outbreak of hepatitis A among young men associated with having sex in public
venues.

Bell A, Ncube F, Hansell A, Davison KL, Young Y, Gilson R, Macdonald N, Heathcock
R, Warburton F, Maguire H.

Merton Sutton and Wandsworth Health Authority, The Wilson, Cranmer Road, Mitcham,
Surrey CR4 4TP. anita.bell@mswha.sthames.nhs.uk

An increase in hepatitis A virus (HAV) infection was noted among young men in the
former Thames regions during 1997. A retrospective case-control study, using a
standardised questionnaire at interview, was conducted in the area most affected 
(London and East Sussex) to investigate the hypothesis that this increase was
mainly among homosexual men and to establish the risk factors associated with
transmission. Forty-eight cases and 161 controls completed questionnaires.
Forty-one cases (85%) described their sexuality as homosexual (p < 0.0001). Cases
were more likely than controls to have eaten shellfish (Odds Ratio (OR) 2.4; 95% 
Confidence Interval (CI) 1.16, 5.04) during the two months before onset of
illness. Cases had more sexual partners (p = 0.015), and more casual sexual
partners (p = 0.007) than controls. Cases were more likely to have had sex in a
gay sauna (OR 3.5; 95% CI 1.53, 8.30), or in a gay club, pub or disco (OR 2.9; 95
CI 1.29, 6.63) than controls. After adjusting for confounding factors, cases were
more likely to have eaten shellfish (adjusted [adj] OR 3.0; 95% CI 1.33, 6.59)
and to have had sex in a gay sauna (adj OR 3.9; 95% CI 1.42, 10.59). Public
health messages need to inform homosexual men about recognised risk factors such 
as eating shellfish and travel abroad to endemic areas, as well as sexual risks. 
Homosexual men can benefit from hepatitis A vaccine. We would suggest that in an 
outbreak situation men who have multiple anonymous partners and have sex in
public venues should be targeted as a priority for health education and
immunisation.

PMID: 11732354 [PubMed - indexed for MEDLINE]

637: Commun Dis Public Health. 2001 Sep;4(3):158-62.

Use of hygiene advice and active immunisation to control an outbreak of hepatitis
A.

Marks PJ, Fey RE, Parry JV, Deakin D, Carlisle D, Neal KR.

Division of Public Health Medicine and Epidemiology, University of Nottingham,
Medical School, Queen's Medical Centre, Nottingham, NG7 2UH.
peter.marks@nottingham.ac.uk

A community outbreak of at least 16 cases of hepatitis A is described. Salivary
antibody testing of 126 children within a school in that community showed only
one case of undiagnosed previous infection. Three other children had received
hepatitis A vaccine previously, and this was reflected in their antibody titres. 
For the schools serving the community control measures included advice on good
hygiene (supervised handwashing and additional cleaning in the schools). All
close contacts of cases (household and childminding contacts and all staff in one
school) were given active immunisation, though two subsequently developed
hepatitis A, 17 and 27 days after vaccination. The use of human normal
immunoglobulin (HNIG) was fully discussed with contacts, but was declined in all 
cases. The low prevalence of previous infection found in the schoolchildren
implies that, in future, few adults will be immune. Public concern about blood
products after the recent Department of Health decision to stop using
British-sourced plasma may be a factor in limiting the uptake of HNIG, especially
as there is now a perceived safer alternative, namely hepatitis A vaccine. Lack
of evidence of spread of disease within the schools involved demonstrates that
good hygiene, especially handwashing, remains the most important element in the
control of hepatitis A.

PMID: 11732353 [PubMed - indexed for MEDLINE]

638: J Gen Virol. 2001 Dec;82(Pt 12):2955-63.

Genetic analysis of hepatitis A virus strains recovered from the environment and 
from patients with acute hepatitis.

Pina S, Buti M, Jardí R, Clemente-Casares P, Jofre J, Girones R.

Department of Microbiology, University of Barcelona, Avd. Diagonal 645, 08028
Barcelona, Spain.

The molecular epidemiology of hepatitis A virus (HAV) was studied by analysing
HAV strains recovered from environmental water samples over a 7 year period and
strains recovered from patients with acute hepatitis over a 5 year period. A
total of 54 samples of raw domestic sewage and 66 samples of river water were
collected. HAV particles were concentrated and detected by nested RT-PCR. HAV
infection in patients with acute hepatitis was serologically diagnosed in 26 of
74 serum samples, which were also analysed by nested RT-PCR. HAV RNA was detected
in 57.4% of sewage samples, 39.2% of Llobregat river water samples, 20% of Ter
river water samples and 61.6% of serum samples. The HAV genomes detected were
characterized further by directly sequencing a region of the 5' non-translated
region, the VP1/2A junction region and, in some samples, the 2B region. Results
showed a 95% prevalence of genotype I, with nearly 50% being either subgenotype
IA or subgenotype IB. Various strains were found simultaneously in both
environmental and clinical samples. These strains were closely related to those
described in distant geographical areas. Genotype IIIA was also found in 5% of
sewage samples and in 12.5% of serum samples. Strains belonging to a common
endemic genotype were not identified. The abundance of HAV in the environment
produces a situation of sanitary risk, especially considering the low prevalence 
of antibodies in the young population.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 11714971 [PubMed - indexed for MEDLINE]

639: Occup Environ Med. 2001 Dec;58(12):762-8.

Hepatitis A in workers exposed to sewage: a systematic review.

Glas C, Hotz P, Steffen R.

Sozialversicher- ungsanstalt des Kantons Zürich (SVA Zürich), Röngtenstrasse 17, 
Zürich, Switzerland.

OBJECTIVES: To assess whether the scientific literature supports the hypothesis
that workers exposed to sewage are at higher risk of hepatitis A (HA). METHODS:
All original papers reporting epidemiological studies published in English,
French, or German which reported on the risk of HA infection in workers exposed
to sewage were eligible. They were identified by several methods and each
original paper was assessed independently with a checklist by two people. Studies
were classified according to the strength of their design. Non-eligible studies
were also examined to assess the impact of publication bias. If the risk
estimates diverged widely, causes for heterogeneity were assessed. A distinction 
was made between seroprevalence studies based on subclinical HA (defined only by 
the presence of anti-HA antibodies) and clinical HA. RESULTS: 17 eligible studies
were identified. No indication of an increased risk of clinical HA could be
found. For seroprevalence the studies with the strongest design suggested a
slightly increased risk of subclinical HA with an odds ratio (OR) <2.5.
Heterogeneity was considerable and precluded a meta-analysis. Considering
non-eligible studies would still decrease the OR. CONCLUSIONS: The systematic
review does not confirm an increased risk of clinical HA in workers exposed to
sewage. An increased risk of subclinical HA cannot be excluded but the
association between seropositivity and exposure to sewage was not strong and
became still weaker if publication bias was taken into account.

Publication Types: 
    Review

PMID: 11706141 [PubMed - indexed for MEDLINE]

640: J Viral Hepat. 2001 Nov;8(6):454-8.

Transmission of hepatitis A through household contact.

Meyerhoff AS, Jacobs RJ.

Capitol Outcomes Research Inc., Alexandria, VA 22310, USA.

In the USA, cost effectiveness assessments support childhood hepatitis A
vaccination in geographical areas with elevated disease rates, but not
nationally. However, these studies do not address the reduction in disease
transmission which may result from routine childhood vaccination. Using decision 
analysis, we estimated the number and age distribution of secondary hepatitis A
cases occurring within households with an index case. Based on the age of the
index case, we determined household size and age composition, the proportion of
household members susceptible to hepatitis A, the probability of disease
transmission, and the likelihood secondarily infected household members would
exhibit symptoms. Our model indicates that for every 100 index cases age 6-11
years, 47.2 secondary infections would occur within households, with 23.1 causing
overt disease. Lower transmission rates for older index cases reflect smaller
household sizes and a higher proportion of household contacts with hepatitis A
immunity. When disease transmission rates are applied to a model simulating
lifetime risks of hepatitis A, universal vaccination of an annual USA birth
cohort is estimated to prevent 24 100 cases of overt disease among household
contacts in addition to 71 000 cases among vaccinees. Sensitivity analysis
provides a wide range of estimates, but even conservative assumptions suggest
routine vaccination would yield an important reduction in secondary cases.
Evaluations of hepatitis A prevention should consider the ability of immunization
to protect household and other personal contacts.

PMID: 11703577 [PubMed - indexed for MEDLINE]

641: J Formos Med Assoc. 2001 Sep;100(9):604-7.

Hepatitis A virus infection in Taipei in 1999.

Tseng HY, Lu CY, Lee CY, Yeh CC, Lin SC, Shih WY, Wu SY, Chang MH, Huang LM.

Department of Pediatrics, National Taiwan University Hospital, 7 Chung-Shan South
Road, Taipei, Taiwan.

BACKGROUND AND PURPOSE: Hepatitis A is a disease that is heavily affected by
sanitation status. Hepatitis A is much less prevalent compared with decades ago
in Taiwan, as in many rapidly developing regions. Hepatitis A vaccine is still
self-paid under the National Health Insurance program and is still not widely
utilized by the general public in Taiwan. This seroepidemiologic study evaluated 
the prevalence of antihepatitis A virus (anti-HAV) seropositivity in Taipei in
1999. METHODS: A total of 1017 serum samples from healthy inhabitants in Taipei
were examined for anti-HAV antibody by qualitative enzyme immunoassay. RESULTS:
The overall seroprevalence rate was 25.2% (255/1013) in the nonvaccinated
population. The seropositivity rate for anti-HAV antibody among children younger 
than 12 months old was 23.3%. The rates dropped to between 1% and 4.8% among
subjects between 1 and 20 years of age. A markedly higher rate of 40% was
observed in subjects aged between 20 and 30 years. The seropositivity rate in
subjects aged 31 to 50 was 80%. More than 90% of subjects older than 50 years
were seropositive. The vaccination rate was low (0.5%). CONCLUSION: Our findings 
indicate that Taipei is an area of intermediate endemicity for hepatitis A virus.
To achieve better herd immunity, a more active approach to the adoption of
hepatitis A vaccine is warranted.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11695275 [PubMed - indexed for MEDLINE]

642: Pediatrics. 2001 Nov;108(5):E78.

The role of child care in a community-wide outbreak of hepatitis A.

Venczel LV, Desai MM, Vertz PD, England B, Hutin YJ, Shapiro CN, Bell BP.

Division of Viral Hepatitis, National Center for Infectious Diseases, National
Center for Health Statistics, and Epidemic Intelligence Service, Epidemiology
Program Office, Centers for Disease Control and Prevention, Atlanta, Georgia
30333, USA.

OBJECTIVE: To evaluate the role of child care centers in a community-wide
hepatitis A epidemic. METHODS: We analyzed surveillance data during an epidemic
in Maricopa County, Arizona, from January to October 1997 and conducted a
case-control study using a sample of cases reported from June to November. Cases 
were physician-diagnosed and laboratory confirmed; control subjects were
frequency matched by age and neighborhood. Information regarding hepatitis A risk
factors, including child care-related exposures, was collected. Characteristics
of all licensed child care centers in the county were obtained through review of 
computerized lists from the Arizona Office of Child Day Care Licensing.
Surveillance data were linked to the child care list to determine which centers
had reported hepatitis A cases. We conducted univariate and multivariate
conditional logistic analyses and calculated population attributable risks (PAR).
RESULTS: In total, 1242 cases (50/100 000 population) were reported. The highest 
rates occurred among people aged 0 to 4 (76/100 000), 5 to 14 (95/100 000), and
15 to 29 (79/100 000) years. The most frequently reported risk factor was contact
with a hepatitis A patient (45%). However, nearly 80% of these contacts were with
individuals who attended or worked in a child care center. Overall, child care
center-related contact could have been the source of infection for 34% of
case-patients. In the case-control study, case-patients (n = 116) and control
subjects (n = 116) did not differ with respect to demographic characteristics. A 
total of 51% of case-patients compared with 18% of control subjects reported
attending or working in a child care setting (direct contact; adjusted odds ratio
[OR]: 6.0; 95% confidence interval [CI]: 2.1-23.0) or being a household contact
of such a person (indirect contact; OR: 3.0; 95% CI: 1.3-8.0). In age-stratified 
analyses, the association between hepatitis A and direct or indirect contact with
child care settings was strongest for children <6 years old and adults aged 18 to
34 years. Household contact with a person with hepatitis A also was associated
with hepatitis A (OR: 9.2; 95% CI: 2.6-58.2). The presence of a child <5 years
old in the household was not associated with hepatitis A. The estimated PAR for
direct child care contact was 23% (95% CI: 16-34), for indirect child care
contact was 21% (95% CI: 13-35), and for any child care contact was 40% (95% CI: 
30-53). Information on 1243 licensed child care centers was obtained, with
capacity ranging from 5 to 479 slots (mean: 87). Thirty-four (2.7%) centers
reported hepatitis A cases. Centers that had a mean capacity of >50 children were
more than twice as likely to have had a reported case of hepatitis A (OR: 2.6;
95% CI: 1.1-6.7). Among the 747 centers that accepted >50 children, having infant
(OR: 3.7; 95% CI: 1.6-8.3), toddler (OR: 6.3; 95% CI: 2.2-20.0), or full-day
service (OR; undefined; 95% CI: 1.7- ~) was associated with having a reported
case of hepatitis A. CONCLUSIONS: In Maricopa County, people associated with
child care settings are at increased risk of hepatitis A, and child care
attendees may be an appropriate target group for hepatitis A vaccination.
Considering the estimated proportion of children who attended child care and were
old enough to receive hepatitis A vaccine (>/=2 years of age) and the calculated 
PAR, approximately 40% of cases might have been prevented if child care center
attendees and staff had been vaccinated. However, epidemiologic studies indicate 
that the proportion of cases that are attributable to child care center exposure 
varies considerably among counties, suggesting that this exposure may be
associated with an increased risk of hepatitis A in some communities but not in
others. To prevent and control hepatitis A epidemics in communities, the Advisory
Committee on Immunization Practices and the American Academy of Pediatrics have
adopted a long-term strategy of routine vaccination of children who live in areas
with consistently elevated hepatitis A rates. After demonstrating
cost-effectiveness, a rule was implemented in January 1999 to require hepatitis A
vaccination of all children who are aged 2 to 5 years and enrolled in a licensed 
child care facility in Maricopa County. Other communities with similar
epidemiologic features might consider routine vaccination of child care center
attendees as a long-term hepatitis A prevention strategy. Consistent with current
recommendations, in communities with persistently elevated hepatitis A rates
where child care center attendance does not play an important role in hepatitis A
virus transmission in the community, child care centers may nonetheless provide a
convenient access point for delivering hepatitis A as well as other routine
childhood vaccinations.

PMID: 11694662 [PubMed - indexed for MEDLINE]

643: Epidemiol Infect. 2001 Oct;127(2):347-51.

Cost analysis of two strategies for preventing hepatitis A virus infection in
Spanish travellers to developing countries.

Bayas JM, González A, Vilella A, San-Martín M, Bertran MJ, Adell C.

Adult Vaccination Centre, UASP IOiBAPS Hospital Clinic, Barcelona, Spain.

Our objectives were to assess the prevalence of anti-hepatitis A (HAV) antibodies
in Spanish travellers to developing countries and to carry out a cost analysis to
allow the comparison of two vaccination strategies. Adult subjects were selected 
from among travellers to developing countries. Information was obtained on age,
sex, destination, previous vaccination against HAV and having received
immunoglobulin. Blood specimens were obtained for anti-HAV antibody
determination. A total of 485 travellers were studied. The prevalence of anti-HAV
antibody was 30.5% (95% CI 26-35). Antibody prevalence was inversely correlated
with age: 9.8% in 18-25 years of age, rising to 75.4% in those 41-55 years of
age. Cost analysis determined that the critical value of prevalence for
vaccination with HAV vaccine was 37.5%. It was concluded that the youngest
Spanish travellers lack anti-HAV antibodies. Vaccination without screening in
those < or = 35 years of age and screening before vaccination for those > 35
years, are the preferred alternatives.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11693513 [PubMed - indexed for MEDLINE]

644: Epidemiol Infect. 2001 Oct;127(2):341-6.

Antibodies to hepatitis A virus in Italian patients with chronic liver disease.

Sagnelli E, Rossi G, Coppola N, Scolastico C, Onofrio M, Filippini P, Chiaramonte
M, Pizzigall E, Aceti A, Spadaro A, Raimondo G, Piccinino F.

Institute of Infectious Diseases, Second University of Naples, Italy.

To improve our knowledge for future hepatitis A virus (HAV) vaccination
strategies we carried out a multicentre study on naturally acquired immunological
protection against HAV in patients with chronic hepatitis in Italy. We enrolled
830 consecutive patients with chronic hepatitis on their first observation at one
of the six Italian liver units participating in the study. Six hundred and
fifty-eight patients (79.3%) were positive for total anti-HAV and 172 (20.7%)
were negative. The anti-HAV negative patients were younger (median age 33, range 
11-78) than the anti-HAV positive (median age 56, 18-87). There was a higher
prevalence of cases with circulating anti-HAV among the 508 patients residing in 
southern Italy than in the 322 residing in northern Italy (88.8% vs. 64%, P <
0.001). No significant difference in the anti-HAV prevalence was observed between
patients from northern Italy and those from southern Italy aged 0-30 years or in 
those over 60 years, while in those 31-60 years old there was a higher prevalence
of anti-HAV positive patients from southern Italy (90.2% vs. 65.8%, P < 0.0001). 
Of the patients with liver cirrhosis in this study, only 3 of the 26 (11.5%) from
northern Italy and 8 of the 228 (3.5%) from southern Italy had no immunological
protection against HAV infection. The data suggest that the number of patients
with chronic liver disease without naturally acquired immunity against HAV is
substantial in Italy, particularly in the north of the country, and that new
vaccination strategies are needed.

Publication Types: 
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 11693512 [PubMed - indexed for MEDLINE]

645: Epidemiol Infect. 2001 Oct;127(2):335-9.

The epidemiology of hepatitis A infection in Palestine: a universal vaccination
programme is not yet needed.

Yassin K, Awad R, Tebi A, Queder A, Laaser U.

Section of International Public Health, School of Public Health, University of
Bielefeld, Germany.

In Palestine, there has been an increase in the reported incidence of acute
hepatitis A virus (HAV) infection since 1995. Since overt clinical disease occurs
only among adults, questions were raised whether or not a shift in the
epidemiology of HAV has occurred. This is generally characterized by a decrease
in the overall incidence rate and a shifting in the mean age of infection towards
adolescence and early adulthood. The need for a vaccination programme is being
discussed. To resolve this issue, we examined the prevalence of anti-HAV in a
representative sample of 396 school children in the Gaza Strip. The prevalence of
anti-HAV was 93.7% (95% CI: 91.3, 96.1%). Stratifying the prevalence by age
showed that 87.8% (95% CI: 78.6, 97%) were HAV antibody positive by the age of 6.
By the age of 14, almost 98% (95% CI: 92.7, 100%) were HAV antibody positive.
This means that the majority of HAV infection is still taking place in early
childhood, when it is usually asymptomatic and of little clinical significance.
The results refuted the shifting epidemiology theory and we recommend that a
vaccination programme against HAV infection is not yet needed. Alternative
explanations for the increase in reported cases are discussed.

PMID: 11693511 [PubMed - indexed for MEDLINE]

646: Epidemiol Infect. 2001 Oct;127(2):327-33.

The epidemiology of hepatitis A in Rio de Janeiro: environmental and domestic
risk factors.

Almeida LM, Werneck GL, Cairncross S, Coeli CM, Costa MC, Coletty PE.

Núcleo de Estudos de Saúde Coletiva, Universidade Federal do Rio de Janeiro.

A serological study of hepatitis A was carried out in low-income areas scheduled 
for a major sanitation programme in Rio de Janeiro, Brazil. Blood spots were
collected by finger puncture and transported on filter paper, and total
antibodies to hepatitis A virus were detected by ELISA. Households were also
interviewed to collect information on their environmental conditions and
socio-economic status. A generalized linear model using a complementary log-log
function was fitted to the data, using the logarithm of age as an explanatory
variable to derive adjusted rate ratios (RR). The risk of infection was greater
among households with 2-3 members per room (RR = 1.4; 95% CI = 1.04-1.8) or more 
than three per room (RR = 1.5; 95% CI = 1.2-2.0). People living on hilltops (RR =
1.5; 95% CI = 1.02-2.2), near to open sewers (RR = 1.2; 95% CI = 1.03-1.5) or
lacking a kitchen (RR = 1.4; 95% CI = 1.08-1.9) were also at greater risk than
others. The number of taps and water-using fittings in the house was associated
with a protective effect (RR = 0.9 for each tap; 95% CI = 0.9-0.98). A
significant protective association was found with maternal education but not with
gender or household income. The results do not suggest a strong association with 
water quality. Ownership of a ceramic water filter was associated with a
protective effect on the margin of significance, but the practice of boiling
drinking-water was not, nor was the type of water source used. The results
suggest that that the risk of infection with hepatitis A is determined by
environmental variables in the domestic and public domains.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11693510 [PubMed - indexed for MEDLINE]

647: J Gen Virol. 2001 Nov;82(Pt 11):2647-52.

Genetic variability of hepatitis A virus in South America reveals heterogeneity
and co-circulation during epidemic outbreaks.

Costa-Mattioli M, Ferre V, Monpoeho S, Garcia L, Colina R, Billaudel S, Vega I,
Perez-Bercoff R, Cristina J.

Laboratorie de Virologie, Institut de Biologie, Centre Hospitalier Regional
Universitaire de Nantes, Rue Quai Moncousu 9, 44093 Nantes, France.

Genetic analysis of selected genome regions of hepatitis A virus (HAV) suggested 
that distinct genotypes of HAV could be found in different geographical regions. 
In order to gain insight into the genetic variability and mode of evolution of
HAV in South America, an analysis was performed of sequence data obtained from
the VP1 amino terminus and the VP1/2A region of HAV strains isolated over a short
period of time in Uruguay, Argentina and Chile. Sequences obtained from 22
distinct HAV isolates were compared with published sequences from 21 different
strains isolated all over the world. Phylogenetic analysis revealed that all
strains isolated belong to a unique sub-genotype (IA). Strains isolated during an
outbreak period showed a higher degree of heterogeneity than anticipated
previously and the co-circulation of different isolates. The genetic variability 
among strains isolated in this region seems to be higher in comparison with
strains isolated in other regions of the world.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11602776 [PubMed - indexed for MEDLINE]

648: Eur J Epidemiol. 2001;17(2):175-82.

Transmission of hepatitis A in hamburg, germany, 1998-1999--A prospective
population based study.

Diel R, Schneider S.

School of Public Health, University of Düsseldorf, Germany. rol.diel@t-online.de

To study the pattern of transmission of HAV in a large urban community a
prospective cohort study was conducted in Hamburg between 1 January 1998 and 31
December 1999. Four hundred and eleven patients were classified as hepatitis A
cases comprising 144 foreign and 267 German persons. Univariate analyses were
carried out to examine differences between socio-demographic, clinical and
behavioural characteristics. To determine independent predictors for HAV
infection a multiple logistic-regression model was used. The principal risk
factor was travel to areas where hepatitis A is endemic, with 32.6% (n= 134/411) 
of all documented cases of hepatitis A. Foreign patients who had acquired the
infection abroad, mostly children, accounted for the majority of these cases. Of 
all 411 cases, 42 (10.2%) were associated with parenteral drug, followed by
day-care or school contact (8.3%; n = 34). Outbreaks contributed to 11.4% of
cases (n = 47), but only 7.1% (n = 29) were household contacts. The low incidence
rate among exposed persons in the households of those infected was similar in the
groups of foreign and German nationals (17/384 = 4.4% and 12/231 = 5.2%,
respectively), which may demonstrate a good hygienic level in general. Our
findings suggest that preventive measures such as the improvement of hygienic
conditions in a defined general population may contribute to a reduced incidence 
of hepatitis A. Nevertheless, because hygienic standards may change with time,
this policy should be supplemented by targeted vaccination of groups at risk.

Publication Types: 
    Comparative Study
    Evaluation Studies

PMID: 11599693 [PubMed - indexed for MEDLINE]

649: Eur J Epidemiol. 2001;17(2):141-4.

Age-specific seroepidemiology of hepatitis A, B, and E infections among children 
in Istanbul, Turkey.

Sidal M, Unüvar E, Oğuz F, Cihan C, Onel D, Badur S.

Department of Pediatrics, Institute of Child Health, Istanbul Medical Faculty,
University of Istanbul, Turkey.

This study was performed for evaluation of seroprevalence of hepatitis A, B, and 
E among children in Istanbul, Turkey. The study group included 909 children who
were 6 months-15 years of age. The children were separated to three age groups:
Group 1 (6 months-4.9 years; n = 321), Group 2 (5.0-9.9 years; n = 318), and
Group 3 (10.0-15.0 years; n = 270). Group I was divided to two subgroups for
evaluation of the maternal antibody sera (6 months-2 years and over 2 years).
Serum IgG anti-HAV, anti-HBc, and anti-HEV were tested by commercial ELISA kits. 
The data were studied by multivariant analysis. In all subjects, seroprevalence
of hepatitis A, B, and E were determined as 29, 15.9, and 2.1% respectively. The 
prevalence of hepatitis A increased with age (p < 0.05; Group 1 15.1% and Group 3
49.6%). Anti-HBc IgG level did not significantly change with age (Group 1 18.6%
and Group 3 15.4%; p > 0.05). The seroprevalence of hepatitis E virus infection
was higher in Group 1 (3.7%) than Group 3 (0.3%; p < 0.05). In Group 1 first
subgroup, between 6 month and 2 year, antibody levels were 12.2, 17.3, and 4.8%
respectively, for anti-HAV IgG, anti-HBc IgG and anti-HEV IgG. Hepatitis A and B 
infection is a community health problem, but hepatitis E infection is low in
children in Istanbul, Turkey. The high positive rate in Group I for IgG anti-HEV 
may be due to maternal antibodies.

Publication Types: 
    Comparative Study
    Evaluation Studies
    Research Support, Non-U.S. Gov't

PMID: 11599687 [PubMed - indexed for MEDLINE]

650: J Med Virol. 2001 Nov;65(3):449-56.

Presumed common source outbreaks of hepatitis A in an endemic area confirmed by
limited sequencing within the VP1 region.

Arauz-Ruiz P, Sundqvist L, García Z, Taylor L, Visoná K, Norder H, Magnius LO.

Department of Virology, Swedish Institute for Infectious Disease Control,
SE-171-82 Stockholm, Sweden.

Hepatitis A virus isolates from anti-HAV IgM positive sera of 70 hepatitis cases 
in two outbreaks and 216 other cases in Central America, 136 sporadic cases and
53 cases from an hyper-endemic region in Costa Rica, were compared by
phylogenetic analyses within the VP1 region. The outbreaks in all 531 cases, in
1992 and 1999, respectively, were presumed water borne. In the first outbreak,
HAV RNA could be detected in 70% of the cases sampled during 6 weeks after onset 
of jaundice. In the hyper-endemic region of San Ramón in Costa Rica, 1,932 cases 
were registered between 1972 and 1985. All isolates belonged to subtype 1A.
Background isolates from Costa Rica and El Salvador tended to form separate
subclusters in the phylogenetic tree construction and were mostly unrelated to
subtype 1A strains from other parts of the world. Based on their amino acid
sequences, four HAV strains, all related to CR326 sampled in Costa Rica in 1960, 
were found to have circulated in the area during the last three decades. However,
on the basis of nucleotide variability the isolates from the outbreaks could be
distinguished from the strains from sporadic cases and sequence analysis could
confirm the epidemiological homogeneity of both outbreaks. In the hyper-endemic
region, 16 different sequences were encountered forming one single subcluster.
Thus, limited sequencing within the VP1 region proved useful to identify
outbreaks of hepatitis A in a highly endemic area, where most strains were local 
and only one subtype was prevalent. Copyright 2001 Wiley-Liss, Inc.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11596077 [PubMed - indexed for MEDLINE]

651: J Hepatol. 2001 Aug;35(2):284-9.

Risk of parenterally transmitted hepatitis following exposure to surgery or other
invasive procedures: results from the hepatitis surveillance system in Italy.

Mele A, Spada E, Sagliocca L, Ragni P, Tosti ME, Gallo G, Moiraghi A, Balocchini 
E, Sangalli M, Lopalco PL, Stroffoli T.

Laboratory of Epidemiology, Istituto Superiore di Sanità, Rome, Italy.

BACKGROUND/AIMS: To evaluate the strength of association between parenterally
transmitted viral hepatitis and specific types of invasive procedures. METHODS:
Data from the surveillance system for type-specific acute viral hepatitis
(SEIEVA) during the period 1994-1999 were used. The association of acute
hepatitis B virus (HBV) and hepatitis C virus (HCV) infection with the potential 
risk factors (odds ratios (OR)) was estimated comparing 3120 hepatitis B and 1023
hepatitis C cases with 7158 hepatitis A cases, used as controls, by multiple
logistic regression analysis. RESULTS: Most procedures resulted in being
associated with the risk of acquiring acute HBV or HCV. The strongest
associations were: for HBV infection, abdominal surgery (adjusted OR = 3.9; 95%
confidence intervals (CI) = 2.0-7.5), oral surgery (OR = 2.7; 95% CI = 1.6-4.5)
and gynaecological surgery (OR = 2.6; 95% CI = 1.2-5.5); for HCV infection,
obstetric/gynaecological interventions (OR = 12.1; 95% CI = 5.6-26.3), abdominal 
surgery (OR = 7.0; 95% CI = 3.2-14.9) and ophthalmological surgery (OR = 5.2; 95%
CI = 1.1-23.2). Biopsy and/or endoscopy were associated with HCV, but not with
HBV infection. CONCLUSIONS: Invasive procedures represent an important mode of
HBV and HCV transmission. Since a large proportion of the adult general
population is exposed to these procedures and an effective HCV vaccine is not yet
available, non-immunological means of controlling iatrogenic modes of
transmission are extremely important.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11580153 [PubMed - indexed for MEDLINE]

652: Arch Med Res. 2001 Sep-Oct;32(5):468-72.

Erratum in:
    Arch Med Res 2002 Mar-Apr;33(2):205.

Vaccination against hepatitis A in children aged 12 to 24 months [corrected].

Abarca K, Ibañez I, Flores J, Vial PA, Safary A, Potín M.

Centro de Investigación Médica, Facultad de Medicina, Pontificia Universidad
Católica de Chile, Santiago, Chile. katia@med.puc.cl

BACKGROUND: Current hepatitis A vaccines are either licensed for children >2
years of age, as in the U.S. or Chile, or >1 year of age, as in Europe and other 
parts of the world. Recent recommendations for immunization against hepatitis A
have included routine vaccination of children in areas or regions of higher
endemicity. However, data on hepatitis A vaccination in toddlers aged between 1
and 2 years are scarce. METHODS: This open clinical study investigated the
reactogenicity and immunogenicity of two doses (0, 6-month schedule) of an
inactivated hepatitis A vaccine (Havrix pediatric, Glaxco SmithKline Biologicals,
Rixensart, Belgium) in 120 seronegative children aged 12-24 months. RESULTS: Pain
at the injection site and irritability were the most frequently reported local
and general symptoms, respectively. No serious adverse events related to the
study vaccine were reported. One month after the first dose, all but one subject 
had antibodies against hepatitis A with a GMT of 159 mIU/mL. After the booster
dose, all had antibodies with a GMT of 2,939 mIU/mL. CONCLUSIONS: Our data show
that the inactivated hepatitis A vaccine was well tolerated by these toddlers and
that the vaccine elicits a good immune response.

Publication Types: 
    Evaluation Studies

PMID: 11578765 [PubMed - indexed for MEDLINE]

653: J Med Virol. 2001 Oct;65(2):233-40.

Genetic analysis of hepatitis A virus outbreak in France confirms the
co-circulation of subgenotypes Ia, Ib and reveals a new genetic lineage.

Costa-Mattioli M, Monpoeho S, Schvoerer C, Besse B, Aleman MH, Billaudel S,
Cristina J, Ferré V.

Laboratorie de Virologie UPRES-EA1156, Institut de Biologie, Centre Hospitalier
Regional Universitaire de Nantes, Nantes, France.

Genetic analysis of selected genome regions of hepatitis A Virus (HAV) suggested 
that distinct genotype could be defined in different geographic locations. In
order to study the degree of genetic variability among HAV isolated during a
single epidemic outbreak, sequences from a 148 base pair segment within the VP1
amino terminal region were obtained for eight distinct HAV isolates from an
outbreak that occurred in North Bretagne (France). These sequences were compared 
among themselves and with published sequences from 30 different strains that
represented different HAV sub-genotypes that were isolated all over the world.
Phylogenetic analysis revealed an extensive genetic heterogeneity among strains
belonging to the same outbreak and revealed co-circulation of sub-genotype IA,
IB, and the presence of IIIA sub-genotype for the first time in a Mediterranean
country. Copyright 2001 Wiley-Liss, Inc.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 11536228 [PubMed - indexed for MEDLINE]

654: Clin Infect Dis. 2001 Oct 1;33(7):1083-5. Epub 2001 Sep 5.

Posttravel hepatitis A: probable acquisition from an asymptomatic adopted child.

Wilson ME, Kimble J.

Division of Infectious Diseases, Mount Auburn Hospital, Cambridge, and Harvard
Medical School, Boston, MA, USA. mary_wilson@harvard.edu

We report a case of acute hepatitis A in an adoptive parent that was probably
acquired from a recently adopted child with asymptomatic, active infection.
Prospective adoptive parents should be protected against hepatitis A because of
potential exposure during travel and the risk of unrecognized active infection in
adopted children.

Publication Types: 
    Case Reports

PMID: 11528585 [PubMed - indexed for MEDLINE]

655: Clin Diagn Lab Immunol. 2001 Sep;8(5):984-92.

Presence of oligoclonal T cells in cerebrospinal fluid of a child with
multiphasic disseminated encephalomyelitis following hepatitis A virus infection.

Oleszak EL, Lin WL, Legido A, Melvin J, Hardison H, Hoffman BE, Katsetos CD,
Platsoucas CD.

Department of Anatomy and Cell Biology, Fels Institute for Cancer Research and
Molecular Biology, Temple University School of Medicine, 3307 North Broad St.,
Philadelphia, PA 19140, USA. eoleszak@astro.temple.edu

We have investigated the clonality of beta-chain T-cell receptor (TCR)
transcripts from the cerebrospinal fluid (CSF) and peripheral blood from a 7-year
old child who developed a multiphasic disseminated encephalomyelitis following an
infection with hepatitis A virus. We amplified beta-chain TCR transcripts by
nonpalindromic adaptor (NPA)-PCR-Vbeta-specific PCR. TCR transcripts from only
five Vbeta families (Vbeta13, Vbeta3, Vbeta17, Vbeta8, and Vbeta20) were detected
in CSF. The amplified products were combined, cloned, and sequenced. Sequence
analysis revealed in the CSF substantial proportions of identical beta-chain of
TCR transcripts, demonstrating oligoclonal populations of T cells. Seventeen of
35 (48%) transcripts were 100% identical, demonstrating a major Vbeta13.3
Dbeta2.1 Jbeta1.3 clonal expansion. Six of 35 (17%) transcripts were also 100%
identical, revealing a second Vbeta13 clonal expansion (Vbeta13.1 Dbeta2.1
Jbeta1.2). Clonal expansions were also found within the Vbeta3 family (transcript
Vbeta3.1 Dbeta2.1 Jbeta1.5 accounted for 5 of 35 transcripts [14%]) and within
the Vbeta20 family (transcript Vbeta20.1 Dbeta1.1 Jbeta2.4 accounted for 3 of 35 
transcripts [8%]). These results demonstrate the presence of T-cell oligoclonal
expansions in the CSF of this patient following infection with hepatitis A virus.
Analysis of the CDR3 motifs revealed that two of the clonally expanded T-cell
clones exhibited substantial homology to myelin basic protein-reactive T-cell
clones. In contrast, all Vbeta TCR families were expressed in peripheral blood
lymphocytes. Oligoclonal expansions of T cells were not detected in the
peripheral blood of this patient. It remains to be determined whether these
clonally expanded T cells are specific for hepatitis A viral antigen(s) or host
central nervous system antigen(s) and whether molecular mimicry between hepatitis
A viral protein and a host protein is responsible for demyelinating disease in
this patient.

Publication Types: 
    Case Reports
    Congresses
    Research Support, U.S. Gov't, P.H.S.

PMID: 11527815 [PubMed - indexed for MEDLINE]

656: Commun Dis Public Health. 2001 Jun;4(2):139-40.

Antibody responses to Hepatitis A vaccine in healthy adults.

Irwin DJ, Millership S.

North Essex Health Authority, Collingwood Road, Witham, Essex CM8 2TT.
David.Irwin@ne-ha.nthames.nhs.uk

Hepatitis A vaccination has been used in a number of settings to control
community outbreaks of the disease. Yet United Kingdom guidance for post-exposure
prophylaxis continues to promote the administration of human normal
immunoglobulin, despite concerns about the administration of human derived blood 
products. Little is known about the time frame of the antibody response to
hepatitis A vaccine which, if rapid, could permit the exclusive use of vaccine
for post-exposure prophylaxis. We report the findings of a pilot study in healthy
adult volunteers given a single dose of Havrix monodose.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11525004 [PubMed - indexed for MEDLINE]

657: Commun Dis Public Health. 2001 Jun;4(2):133-5.

An investigation of the potential risk of an HAV outbreak in a prison population 
following the introduction of cases from a community outbreak.

Skidmore S, Parry JV, Nottage P.

Shrewsbury & Telford Public Health Laboratory, Shrewsbury.
sskidmore@mids.phls.nhs.uk

Increasing Hepatitis A (HAV) infection has been reported in communities in which 
there is a high level of intravenous drug use. Several cases were identified in a
local prison and since the risk of transmission within the prison was felt to be 
high, it was decided to determine the prevalence of HAV antibodies in the prison 
population and therefore the number of susceptible inmates. Oral fluid was
collected from 269 prisoners for testing for antibodies to HAV. Both IgM and IgG 
anti-HAV were assessed so that the percentage susceptible and the number recently
infected could be ascertained. Eight inmates had evidence of a recent infection. 
Of the remaining 261, only 56 (21%) were immune to HAV. Therefore vaccination
against HAV in addition to HBV should be considered for intravenous drug users
and for prisoners remanded from a community where infection is known to be
occurring.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11525002 [PubMed - indexed for MEDLINE]

658: CMAJ. 2001 Aug 7;165(3):293-7.

Past infection with hepatitis A virus among Vancouver street youth, injection
drug users and men who have sex with men: implications for vaccination programs.

Ochnio JJ, Patrick D, Ho M, Talling DN, Dobson SR.

Vaccine Evaluation Center, British Columbia's Children's Hospital and University 
of British Columbia. jochnio@interchange.ubc.ca

BACKGROUND: In Canada, inactivated hepatitis A vaccines are targeted selectively 
at those at increased risk for infection or its complications. In order to
evaluate the need for routine hepatitis A vaccination programs in Vancouver for
street youth, injection drug users (IDUs) and men who have sex with men (MSM), we
determined the prevalence of antibodies against hepatitis A virus (HAV) and risk 
factors for HAV in these groups. METHODS: The frequency of past HAV infection was
measured in a sample of Vancouver street youth, IDUs and MSM attending outreach
and STD clinics and needle exchange facilities by testing their saliva for
anti-HAV immunoglobulin G. A self-administered, structured questionnaire was used
to gather sociodemographic data. Stepwise logistic regression was used to
evaluate the association between presumed risk factors and groups and past HAV
infection. RESULTS: Of 494 study participants, 235 self-reported injection drug
use, 51 were self-identified as MSM and 111 met street youth criteria. Positive
test results for anti-HAV were found in 6.3% of street youth (95% confidence
interval [CI] 2.6%-12.6%), 42.6% (95% CI 36.2%-48.9%) of IDUs and 14.7% (95% CI
10.4%-19.1%) of individuals who denied injection drug use. Among men who denied
injection drug use, the prevalence was 26.3% (10/38) for MSM and 12% (21/175) for
heterosexuals. Logistic regression showed that past HAV infection was associated 
with increased age and birth in a country with high rates of hepatitis infection.
Injection drug use among young adults (25-34 years old) was a significant risk
factor for a positive anti-HAV test (p = 0.009). MSM were also at higher risk for
past HAV infection, although this association was nominally significant (p =
0.07). INTERPRETATION: Low rates of past HAV infection among Vancouver street
youth indicate a low rate of virus circulation in this population, which is
vulnerable to hepatitis A outbreaks. An increased risk for HAV infection in IDUs 
and MSM supports the need to develop routine vaccination programs for these
groups also.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11517645 [PubMed - indexed for MEDLINE]

659: Z Gastroenterol. 2001 Jul;39(7):519-22.

Cholestatic hepatitis A complicated by acute renal insufficiency.

Wolf M, Oneta CM, Jornod P, Seld D, Wauters JP, Blum AL, Delarive J.

Department of Internal Medicine, Centre Hospitalier Universitaire Vaudois,
Lausanne, Switzerland.

31 cases of non-fulminant hepatitis A complicated by acute renal insufficiency
are reported in the literature. Two-thirds of those patients needed dialysis,
usually when depending on the severity of their hyperbilirubinemia. This report
concerns the first published case of non-fulminant cholestatic hepatitis A
complicated by acute renal insufficiency in which a spontaneous remission of
renal function occurred without need for dialysis despite a very severe
hyperbilirubinemia.

Publication Types: 
    Case Reports

PMID: 11505332 [PubMed - indexed for MEDLINE]

660: Indian J Gastroenterol. 2001 Jul-Aug;20(4):132-5.

Comment in:
    Indian J Gastroenterol. 2002 Jan-Feb;21(1):40-1.

Seroepidemiology of hepatitis A infection in India: changing pattern.

Mall ML, Rai RR, Philip M, Naik G, Parekh P, Bhawnani SC, Olowokure B, Shamanna
M, Weil J.

Marwari Relief Society Hospital and The Calcutta Research Institute.

OBJECTIVE: Recent changes in the epidemiology of hepatitis A virus (HAV)
infection and the availability of effective vaccines have renewed interest in
this infection. We determined the age-related prevalence of anti-HAV antibodies
in India and looked for differences by known risk factors for HAV infection.
METHODS: In this prospective study, serum samples obtained from 1612 subjects
aged 1 to 60 at six centers in five cities (Calcutta, Cochin, Indore, Jaipur and 
Patna) during the period February to August 1998 were tested for anti-HAV
antibodies. Demographic and socio-economic information was obtained by
questionnaire. RESULTS: The overall seroprevalence rate was 65.9%, varying from
26.2% to 85.3% in various cities; there was no difference between males and
females. Seropositivity increased with age from 52.2% in the 1-5 year age group
to 80.8% in those aged 16 years or more. Seroprevalence rates were significantly 
lower in those aged 1-5 years compared with other age groups (p<0.0001). There
was no difference in seroprevalence between those with monthly family income <Rs 
5000 and >Rs 5001. Multivariate analysis showed that anti-HAV seroprevalence
varied significantly by source of water supply, being highest when the supply was
municipal. CONCLUSION: Our results indicate an epidemiological pattern of
intermediate endemicity. This finding has public health implications as it
indicates that a significant proportion of the Indian adolescent and adult
population is at risk of HAV infection.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11497169 [PubMed - indexed for MEDLINE]

661: J Hepatol. 2001 Jul;35(1):112-9.

Analysis of full-length hepatitis A virus genome in sera from patients with
fulminant and self-limited acute type A hepatitis.

Fujiwara K, Yokosuka O, Fukai K, Imazeki F, Saisho H, Omata M.

First Department of Internal Medicine, Chiba University School of Medicine,
Japan.

BACKGROUND/AIMS: Type A hepatitis still poses a considerable problem worldwide.
Why some patients progress to fulminant type A hepatitis and others do not is
still unknown. To examine whether genomic differences of hepatitis A virus (HAV) 
are responsible for the severity of the disease, we analyzed the whole HAV
genomes from patients with fulminant and self-limited acute type A hepatitis.
METHODS: Sera from three patients with sporadic type A fulminant hepatitis (FH)
and three patients with acute hepatitis (AH) were examined for HAV RNA.
Full-length nucleotide sequences were determined using long reverse transcription
polymerase chain reaction, 5' and 3' rapid amplification of cDNA ends methods,
and direct sequencing. The amino acid sequences were deduced from the nucleotide 
sequences. RESULTS: HAV RNA was detected in all six patients examined. From the
sequence of viral protein 1/2A, all cases were revealed to be genotype IA. By
comparing with genotype IA, wild-type HAV strain GBM, the analysis of whole
genomes from the six cases showed no specific substitutions between FH and AH.
Completely identical nucleotide sequences were observed at 3' non-translated
region (NTR) in all six cases. In 5'NTR, less nucleotide substitutions were found
in FH than in AH, and in the non-structural protein 2B region, a little more
amino acid substitutions seemed to be found in FH than in AH. CONCLUSIONS: This
study showed that full-length HAV could be analyzed from serum samples. Although 
there were no unique nucleotide or amino acid substitutions, possible
associations were suggested between the severity of type A hepatitis and the
nucleotide substitutions in 5'NTR and the amino acid substitutions in 2B.

Publication Types: 
    Comparative Study

PMID: 11495028 [PubMed - indexed for MEDLINE]

662: Am J Med Qual. 2001 Jul-Aug;16(4):145-8.

Seroprevalence of hepatitis A among hospital dietary workers: implications for
screening and immunization.

Alagappan K, Barnett B, Napolitano A, Gressin J, Auerbach C.

Department of Emergency Medicine, Long Island Jewish Medical Center, Long Island 
Campus, Albert Einstein College of Medicine, New Hyde Park, NY, USA.

Hepatitis A is a self-limited, virally mediated infection of the liver. The usual
mode of transmission is by the fecal-oral route. Employees of food-service
establishments who are infected with the hepititus A virus can transmit the
disease when handling food products. The Centers for Disease Control and
Prevention recommends the use of the hepatitis A vaccine among dietary workers
who may be at risk for contracting and spreading the disease. Because hepatitis A
infection can often be a subclinical disease, the incidence of cases reported is 
not indicative of its true prevalence. The objective of this study was to
document the seroprevalence of hepatitis A among hospital dietary workers.
Dietary workers at a suburban hospital were interviewed to determine if they had 
been exposed to hepatitis A and if they had a history of hepatitis A infection.
Serum was obtained from each subject and tested for the presence of hepatitis A
antibodies. The Abbott HAVAB EIA kit was used for the detection of immunoglobulin
G (IgG) and IgM hepatitis A antibodies. Of 119 subjects, 56 (47%) were women, and
63 (53%) were men; the subjects had a mean age of 42 years (range, 20-66).
Fifty-one subjects (43%) were born in the United States, and 68 subjects (57%)
were born outside of the United States. Of the 119 subjects, only 2 (2%) had a
known history of hepatitis A infection, yet 67 (56%) had hepatitis A titers; 52
(44%) were susceptible to the disease. One subject had received the hepatitis A
vaccine. Fifty-five of 68 foreign-born subjects (81%; 95% confidence interval,
71-91%) had hepatitis A antibodies versus 12 of 51 US-born subjects (24%; 95%
confidence interval, 12-36%). The foreign-born subjects had a mean age of 28
years at the time of their arrival in the United States. In conclusion, a large
number of foreign-born hospital dietary workers have hepatitis A antibodies
without a history of disease. Immunization of this group of dietary workers may
not have any beneficial effects, nor is it cost-effective.

PMID: 11477959 [PubMed - indexed for MEDLINE]

663: Transplantation. 2001 Jul 27;72(2):272-6.

Safety and efficacy of hepatitis A vaccination in liver transplantation
recipients.

Arslan M, Wiesner RH, Poterucha JJ, Zein NN.

Division of Gastroenterology and Hepatology and Internal Medicine, Mayo Clinic,
200 First Street SW, Rochester, MN 55905, USA.

OBJECTIVE: Vaccination against hepatitis A (HAV) has been shown to be safe and
effective in healthy subjects and in patients with chronic liver disease (CLD).
The safety and efficacy of HAV vaccines in liver transplant (OLT) recipients have
not been established. The objective of this study is to assess the safety and
efficacy of inactivated hepatitis A vaccine in OLT recipients. METHODS:
Thirty-seven HAV seronegative OLT recipients were enrolled. Patients received two
doses of vaccine 6 months apart. Postvaccination IgG anti-HAV were determined at 
1, 6, and 7 months after the first vaccine dose. Side effects were monitored for 
3 days after each vaccination shot. An unvaccinated control group (45 patients)
was followed for evidence of seroconversion. Seroconversion rate was also
compared with those reported in healthy patients and in patients with chronic
liver disease. RESULTS: Testing was available for all the cases at 1 month, and
for 26 and 23 patients at 6 and 7 months, respectively. Only 3 of 37 patients
(8%) had seroconversion at 1 month. At 6- and 7-month time points, 5 of 26 (19%) 
and 6 of the 23 (26%) patients had seroconversion, respectively. Vaccine
responders had higher total white blood cell count and lymphocyte count and were 
further out from transplant compared with nonresponders. None of the unvaccinated
patients had seroconversion over the follow-up time. Seroconversion rates in OLT 
recipients were significantly lower than that reported in healthy individuals
(P=0.001) or in pre-OLT patients with CLD (P=0.001). All patients tolerated the
vaccine well. CONCLUSIONS: HAV vaccination is safe in OLT recipient. Efficacy of 
HAV vaccination in OLT recipients, as measured by a commercially available enzyme
immunoassay, is low and alternative strategies should be developed to improve
response rate.

Publication Types: 
    Clinical Trial
    Comparative Study
    Controlled Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 11477352 [PubMed - indexed for MEDLINE]

664: J Med Virol. 2001 Aug;64(4):402-9.

Experimental hepatitis A virus infection in guinea pigs.

Hornei B, Kämmerer R, Moubayed P, Frings W, Gauss-Müller V, Dotzauer A.

Institute of Medical Microbiology and Hygiene, Medical University of Luebeck,
Luebeck, Germany.

Although many of the properties of hepatitis A virus (HAV) are known, several
aspects of HAV pathogenesis are still not understood, such as the mechanism
underlying the hepatotropism or HAV replication in extrahepatic sites. Detailed
studies of these aspects were hampered mostly by the lack of accessible animal
models, since only nonhuman primates are susceptible to experimental infections. 
An alternative animal model would also be of interest to assess the primary
replication site and for the evaluation of the safety and efficacy of vaccines. A
study was undertaken to determine whether HAV can infect guinea pigs and whether 
they are useful as a model for studying aspects of HAV pathogenesis and for the
evaluation of vaccines. HAV variants adapted to primate or guinea pig tissue
culture were used to inoculate guinea pigs intraperitoneally and by the oral
route. The animals were observed for clinical disease, shedding of HAV in stools,
viremia, seroconversion, evidence for liver damage by biochemical liver function 
tests, virus presence in the liver, development of hepatic histopathological
changes, and occurrence of HAV in extrahepatic organs. The animals developed an
active, clinically inapparent infection with specific histopathological changes
in the liver. Although virus replication occurred, as shown by RT-PCR and
isolation of infectious virus from feces and serum, it seems unlikely that guinea
pigs are suitable for studying the clinical features of hepatitis A, because the 
clinical and laboratory parameters remained normal. However, guinea pigs appear
useful for studying some aspects of HAV pathogenesis and for testing the safety
of vaccines. Copyright 2001 Wiley-Liss, Inc.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11468723 [PubMed - indexed for MEDLINE]

665: Water Sci Technol. 2001;43(12):61-5.

Human enteric viruses in Coquina clams associated with a large hepatitis A
outbreak.

Bosch A, Sánchez G, Le Guyader F, Vanaclocha H, Haugarreau L, Pintó RM.

Department of Microbiology, University of Barcelona, 08028 Barcelona, Spain.
albert@porthos.bio.ub.es

An outbreak of hepatitis A, affecting 183 people, occurred in Valencia (Spain).
Epidemiological evidence pointed to an association of the outbreak with
consumption of Coquina clams (Donax sp), imported frozen from Peru. Shellfish
were analysed for the presence of hepatitis A virus (HAV), enteroviruses,
rotaviruses, astroviruses, caliciviruses and hepatitis E virus. HAV was detected 
in 75% of assayed shellfish samples. Other enteric viruses were occasionally
found in the same samples. Molecular epidemiological analysis of fragments of the
VP1/2A and the 5' end of the genome from shellfish and sera isolates, revealed
the presence of six variants belonging to a single genotype.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11464770 [PubMed - indexed for MEDLINE]

666: J Viral Hepat. 2001 Jul;8(4):293-303.

Changing epidemiology of hepatitis A and hepatitis E in urban and rural India
(1982-98).

Arankalle VA, Chadha MS, Chitambar SD, Walimbe AM, Chobe LP, Gandhe SS.

Hepatitis Division, National Institute of Virology, Pune, India.
aarankalle@hotmail.com

The epidemiology of hepatitis A virus (HAV) and hepatitis E virus (HEV) was
assessed among age-stratified urban high socioeconomic, lower middle
socioeconomic status and rural populations from western India in 1998. When
compared with previous surveys, a clear shift from high to intermediate
endemicity of HAV was evident only for higher socioeconomic population (1982-98),
raising the possibility of outbreaks of hepatitis A in this category. A decrease 
in anti-HAV positivity was noted in rural children aged 6-10 years. Lower
circulation of HEV was noted among < 25-year-old urban higher socioeconomic and
rural individuals. For both viruses, the lower middle socioeconomic populations
were comparable in 1982 and 1998. Socioeconomic status and family size (odds
ratio = 23 and 1.6, respectively) were independently associated with anti-HAV
positivity. Age, lower middle socioeconomic status and well water were
significant independent variables for HEV infection (odds ratio = 5.7, 2.4 and
1.9, respectively). Hence, vaccination policy for hepatitis A needs to be
reviewed.

PMID: 11454182 [PubMed - indexed for MEDLINE]

667: Eur J Clin Invest. 2001 Jul;31(7):617-22.

Changes of gallbladder and gastric dynamics in patients with acute hepatitis A.

Portincasa P, Moschetta A, Di Ciaula A, Palmieri VO, Milella M, Pastore G,
Palasciano G.

University Medical School, Bari, Italy, Division of Internal Medicine, Bisceglie,
Italy. p.portincasa@semeiotica.uniba.it

Transient alterations of gallbladder morphology and dynamics have been reported
in patients with during acute hepatitis A. The presence of dyspepsia also
suggests involvement of gastric motility. During a 60-day follow-up, we
investigated gallbladder and gastric motility in relation to dyspepsia in acute
viral hepatitis A patients. Twenty patients were assessed at referral (day 0) and
at days 7, 21, 42 and 60 and compared with 20 healthy volunteers. Gallbladder
morphology and motility and gastric motility were assessed in the fasting and
postprandial period by functional ultrasonography using a liquid test meal.
Dyspeptic symptoms were scored. At day 0, fasting gallbladder volume was 5.9 +/- 
1.3 mL, 32.6 +/- 4.6 mL, and 21.5 +/- 1.9 mL (mean +/- SE) in patients with
gallbladder sludge (n = 7), without sludge (n = 13) and controls, respectively (P
< 0.05 in sludge vs. no sludge and controls; P < 0.05 in no sludge vs. controls, 
ANOVA). Small fasting gallbladder volume in patients with sludge increased and
sludge disappeared within 7 days. At day 0, patients with sludge also had
increased thickness of fasting gallbladder wall and increased serum transaminase 
levels compared with patients without sludge and controls. Gallbladder
contraction was similar in patients and controls. However, patients had delayed
gastric emptying, which positively correlated with dyspepsia score. Gallbladder
morphological changes observed in the acute phase of hepatitis A are transient
and are associated with hepatocellular damage. Gastric emptying is delayed during
the first week of disease and is associated with dyspeptic symptoms.

PMID: 11454017 [PubMed - indexed for MEDLINE]

668: Aviat Space Environ Med. 2000 Dec;71(12):1178-80.

Prevalence of hepatitis A, B, C, and E antibody in flying airline personnel.

Andenaes S, Lie A, Degré M.

Health, Environment & Safety Dept., Scandinavian Airlines System, Oslo, Norway.

OBJECTIVES: The aim of the study was to detect the prevalence of antibodies
against hepatitis A, B, C, and E viruses in flying airline personnel, and to
determine the necessity of hepatitis A vaccination to prevent such infections
related to occupational exposure. METHODS: Antibodies against hepatitis A (HAV), 
B (HBV), C (HVC), and E (HEV) were tested for using standard enzyme immunoassay
in airline personnel, 208 flying personnel, 199 ground crew, and 204 employees
from companies not involved in travel activities. RESULTS: Prevalence of
antibodies against HAV was less than 5% in each group, and there was no
significant difference between the three groups. Prevalence of antibodies against
HEV was significantly higher in flying personnel (3.4%) than in the control
groups. Prevalence of antibodies against HBV and HCV was low in each of the three
groups and there were no differences between the three groups. CONCLUSIONS:
Infection with HAV, HBV and HCV does not seem to represent an occupational hazard
to flying personnel. It is possible that flying personnel are exposed to
infection with HEV, however, presently no vaccine is available.

PMID: 11439715 [PubMed - indexed for MEDLINE]

669: Eur J Epidemiol. 2000;16(11):1069-72.

Seroprevalence of hepatitis A, B and C markers in Greek warship personnel.

Mazokopakis E, Vlachonikolis J, Philalithis A, Lionis C.

Clinic of Internal Medicine, Naval Hospital of Athens, Greece.
NNA@ath.forthnet.gr

A seroepidemiological study was conducted to assess the seroprevalence of
hepatitis A, B and C markers in 285 males (mean age: 24.4+/-4.4 years) aboard a
Greek warship. Two hundred and sixty three serum samples were tested. None was
found to be positive for HAV antibodies, three persons (1.1%) were positive for
HBsAg, four persons (1.5%) were positive for anti-HBc and one person (0.4%) was
positive for anti-HCV. Forty-five persons (17.1%) had developed titles anti-HBs >
10 IU/L. The establishment of a vaccination policy against hepatitis A among
warship personnel is strongly recommended.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11421478 [PubMed - indexed for MEDLINE]

670: J Clin Gastroenterol. 2001 Jul;33(1):20-6.

Risks associated with hepatitis A and hepatitis B in patients with hepatitis C.

Koff RS.

University of Massachusetts Memorial Medical Center, 55 Lake Avenue North,
Worcester, MA 01655, USA. koffr@ummhc.org

Individuals with hepatitis C virus (HCV) are at risk for acquiring hepatitis A
virus (HAV) or hepatitis B virus (HBV) because of shared risk factors. A number
of organizations recommend vaccination against HAV and HBV for patients with HCV.
The rationale for vaccinating these patients is to prevent hepatic
superinfections. Acute HAV superinfection causes more severe disease, acute
hepatic failure, and higher fatality rates in patients with underlying chronic
liver disease, specifically chronic HBV infection and chronic HCV infection.
Available data, although limited, suggest that HBV coinfection with HAV and HCV
causes more severe hepatic injury than infection with HAV or HCV alone. At
standard doses, hepatitis A and hepatitis B vaccines are safe and immunogenic in 
patients with mild-to-moderate hepatitis C or chronic liver disease. Regardless
of disease severity, vaccination should be routinely administered to patients
upon diagnosis of HCV infection. Early vaccination is important because response 
to vaccination is reduced as liver disease progresses. Prevaccination and
postvaccination serology testing is recommended in specific populations. A new
combination hepatitis A and hepatitis B vaccine has been shown to be as safe and 
effective as monovalent hepatitis A and B vaccines and is currently under review 
by the United States Food and Drug Administration. A combination vaccine would
offer ease of administration and convenience and could increase compliance in
patients with hepatitis C or other chronic liver disease: two groups that should 
be more aggressively targeted by healthcare professionals.

Publication Types: 
    Review

PMID: 11418785 [PubMed - indexed for MEDLINE]

671: Isr Med Assoc J. 2001 May;3(5):347-51.

The changing epidemiology of viral hepatitis A in Israel.

Green MS, Aharonowitz G, Shohat T, Levine R, Anis E, Slater PE.

Israel Center for Disease Control, Ministry of Health, Tel-Hashomer, Israel.
m.green@trendline.co.il

BACKGROUND: Between 1970 and 1979, there was an increase in the incidence of
viral hepatitis in Israel with a shift of peak incidence to an older age in the
Jewish population, followed by a declining trend during the early 1980s. In July 
1999 universal immunization of infants against hepatitis A was introduced.
OBJECTIVE: To evaluate the chan-ges in the epidemiology of viral hepatitis A in
Israel during the past decade. METHODS: Viral hepatitis is a notifiable disease
in Israel and cases are reported to the regional health offices, which in turn
provide summary reports to the Ministry of Health's Department of Epidemiology.
The data in this study were derived from the summary reports and from results of 
seroprevalence studies. RESULTS: Following the increase in the incidence of
reported viral hepatitis (mainly due to type A) between 1970 and 1979, the rates 
then stabilized and around 1984 began to decline until 1992. Since then there has
been a slight increase. Whereas until 1987 the rates were consistently higher in 
the Jewish population, since then they are higher in the Arab population. The
shift in the peak age-specific incidence from the 1-4 to the 5-9 year age group
observed in the Jewish population around 1970 occurred 20 years later in the Arab
population. The previously described seasonality is no longer evident. Recent
seroprevalence studies indicate that by age 18 years only about 30-40% of the
Jewish population have anti-hepatitis A antibodies. CONCLUSIONS: The decline in
the incidence of hepatitis probably reflects the changing socioeconomic condition
occurring at different times in the two major population groups. Since hepatitis 
A accounts for almost all the acute viral hepatitis in Israel, the universal
vaccination of infants introduced in 1999 should substantially lower the
morbidity within the next few years.

PMID: 11411199 [PubMed - indexed for MEDLINE]

672: J Nephrol. 2001 Mar-Apr;14(2):115-9.

Immunoglobulin A nephropathy associated with hepatitis A virus infection.

al-Homrany M.

King Khalid University, Abha Medical College, Department of Medicine, (Nephrology
Division), Abha, Saudi Arabia. mhomrany@yahoo.com

Renal involvement in association with nonfulminant hepatitis A virus (HAV)
infections have been reported infrequently and when present have been
characterized by mild proteinuria, microscopic hematuria and slight urinary
sediment abnormalities. Acute renal failure and nephrotic syndrome are extremely 
rare complications. This report describes a case of acute renal failure and
nephrotic syndrome following a nonfulminant course of HAV infection with biopsy
proven immunoglobulin A nephropathy. The cause of acute renal failure in this
case is primarily due to tubulointerstitial nephritis secondary to pigment
toxicity.

Publication Types: 
    Case Reports

PMID: 11411012 [PubMed - indexed for MEDLINE]

673: ILAR J. 2001;42(2):161-77.

Animal models of hepatitis A and E.

Purcell RH, Emerson SU.

Hepatitis Viruses and Molecular Hepatitis Sections, Laboratory of Infectious
Diseases, National Institute of Allergy and Infectious Diseases, National
Institutes of Health, Bethesda, Maryland, USA.

Several useful animal models for both hepatitis A and E have been identified,
characterized, and refined. At present, all of the best models utilize nonhuman
primates: chimpanzees, tamarin species, and owl monkeys for hepatitis A; and
macaque species, chimpanzees, and owl monkeys for hepatitis E. Pigs may prove
useful for some studies of hepatitis E, and it is hoped that serological evidence
of widespread infection of rats with an HEV-like agent may lead to the
development of an animal model based on laboratory rats. As has been the case for
each of the hepatitis viruses as they have been discovered, the development of
useful and reproducible animal model systems has been critical for moving the
field forward as expeditiously as possible.

Publication Types: 
    Review

PMID: 11406718 [PubMed - indexed for MEDLINE]

674: J Food Prot. 2001 Jun;64(6):877-80.

Closed-circuit system for the depuration of mussels experimentally contaminated
with hepatitis A virus.

De Medici D, Ciccozzi M, Fiore A, Di Pasquale S, Parlato A, Ricci-Bitti P, Croci 
L.

Laboratorio Alimenti, Istituto Superiore di Sanità, Roma, Italy. demedici@iss.it

In Italy, the consumption of raw or slightly cooked mussels represents the most
important risk factor for the transmission of hepatitis A virus (HAV). Although
there exist effective methods for the bacterial depuration of contaminated
mussels, these methods are poorly effective on enteric viruses. The objective of 
the present study was to evaluate the effectiveness of a closed-circuit
depuration system that uses both ozone and UV light for disinfecting water and
that allows salinity and temperature, important parameters for the metabolism of 
mussels (Mytilus galloprovincialis), to be maintained at constant levels. The
results showed that this depuration method decreased the viral load (from 1.72
log 50% tissue culture infective dose [TCID50] ml(-1) to <1 log TCID50 ml(-1)
within 24 h and from 3.82 log TCID50 ml(-1) to <1 log TCID50 ml(-1) within 48 h).
However, in both cases, after 120 h of depuration, a residual amount of virus
capable of replicating in cells was detected. These results show that depuration,
even if performed with advanced systems, may not guarantee the absence of virus.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11403143 [PubMed - indexed for MEDLINE]

675: Vaccine. 2001 Jun 14;19(27):3615-9.

Hepatitis A control in a refugee camp by active immunization.

Kaic B, Borcic B, Ljubicic M, Brkic I, Mihaljevic I.

Department of Epidemiology, Croatian National Institute of Public Health,
Rockefellerova 7, HR-10000 Zagreb, Croatia. berislav.borcic@zg.tel.hr

An outbreak of hepatitis A occurred among children of a refugee camp in Croatia. 
In order to disrupt the outbreak, we decided to vaccinate children from 1 to 15
years of age in the camp, in addition to intensified general preventive measures.
Assuming high prevalence of hepatitis A virus antibodies within this population, 
we conducted anti-HAV testing of the children eligible for vaccination. Of 108
children tested, 74 (68.5%) were anti-HAV positive. We vaccinated 34 children.
One month after vaccination 31 previously negative children were tested for
anti-HAV and 30 of them were found positive, suggesting a seroconversion rate of 
96.8%. One child fell ill 5 days after vaccination, after whom no new cases of
hepatitis A occurred. Thus we conclude that active immunization is a successful
means of stopping an outbreak of hepatitis A.

PMID: 11395194 [PubMed - indexed for MEDLINE]

676: J Hepatol. 2001 Apr;34(4):625-30.

Allogenic bone marrow transplantation with a donor presenting with an acute
hepatitis A.

Ghez D, Nicand E, Ferré V, de Tailly PD, Coppo P, Lenoir B, Buisson Y, Nedellec
G, de Revel T.

Service d'Hématologie, Hĵpital d'Instruction des Armies Percy, Clamart, France.

We report the unique occurrence of an allogenic bone marrow transplantation
performed as the donor was suffering from an acute hepatitis A. The bone marrow
was contaminated at the time of collection, as demonstrated by hepatitis A virus 
(HAV) RNA detected by RT-PCR. Hepatitis A virus infection in such a situation
could have resulted in a severe liver disease in the recipient. However, although
we could demonstrate that the recipient had been infected, he did not develop a
symptomatic hepatitis A but only minor disturbances of liver function tests
between days 35 and 55. Both the postponement of the transplantation and the use 
of intravenous polyvalent immunoglobulins have probably played a key role in
decreasing the viral load and allowing a rapid clearance of the virus. A possible
role of the grafted immune system might also be envisaged, as suggested by the de
novo synthesis of IgM in the recipient.

Publication Types: 
    Case Reports

PMID: 11394666 [PubMed - indexed for MEDLINE]

677: Exp Biol Med (Maywood). 2001 May;226(5):420-8.

Cholangiohepatitis and inflammatory bowel disease induced by a novel
urease-negative Helicobacter species in A/J and Tac:ICR:HascidfRF mice.

Shomer NH, Dangler CA, Schrenzel MD, Whary MT, Xu S, Feng Y, Paster BJ, Dewhirst 
FE, Fox JG.

Division of Comparative Medicine, Massachusetts Institute of Technology,
Cambridge 02139, USA.

Helicobacter bilis and H. hepaticus, both urease-positive intestinal
helicobacters of mice, have been shown experimentally to induce proliferative
typhlocolitis in scid mice. We recently isolated a urease-negative Helicobacter
sp. (H. sp.) that also induced proliferative typhlocolitis in pilot studies in
scid mice. To determine the pathogenic potential of H. sp. in immunocompromised
and immunocompetent mice, 5-week old male A/J or Tac:Icr:Ha(ICR)-scidfRF mice
were inoculated by intraperitoneal (IP) injection with approximately 3 x 10(7)
colony-forming units (CFU) of H. sp. Mice were necropsied at various time points 
postinoculation (PI). Sham-inoculated mice had no clinical, gross, or
histopathological lesions. In contrast, scid mice inoculated IP with H. sp. had
severe hemorrhagic diarrhea and decreased weight gain at 2, 7, and 18 weeks
postinoculation (PI), with severe proliferative typhlocolitis, phlebothrombosis, 
and hepatitis. A/J mice had no clinical signs, but had mild to moderate
proliferative typhlocolitis and moderate to marked cholangiohepatitis at 7 and 24
weeks PI. A/J mice infected with H. sp. developed robust immune responses of a
predominant Th1 type. This report demonstrates that infection with a
urease-negative helicobacter can cause inflammatory bowel disease (IBD) and
hepatitis in scid and immunocompetent A/J mice. These results provide a new model
of IBD and cholangio-hepatitis associated with a specific urease-negative, novel 
H. species.

Publication Types: 
    Research Support, U.S. Gov't, P.H.S.

PMID: 11393169 [PubMed - indexed for MEDLINE]

678: Hepatology. 2001 Jun;33(6):1512-7.

Protracted, but not acute, hepatitis A virus infection is strongly associated
with HLA-DRB*1301, a marker for pediatric autoimmune hepatitis.

Fainboim L, Cañero Velasco MC, Marcos CY, Ciocca M, Roy A, Theiler G, Capucchio
M, Nuncifora S, Sala L, Zelazko M.

División Inmunogenogenética, Hospital de Clínicas, and Departmento de
Microbiología e Immunología, Facultad de Medicina, Universidad de Buenos Aires,
Argentina. inmuno@fmed.uba.ar

HLA alleles are known to be associated with susceptibility to develop autoimmune 
hepatitis (AH), and hepatitis A virus (HAV) infection is postulated as a putative
trigger for AH. We investigated whether HLA may influence the outcome of the HAV 
infection by studying 67 children with self-limited and 39 children with
protracted forms of this infection. HLA typing of the uncomplicated forms showed 
no significant increase of any HLA class I or II alleles. In contrast, DRB1*1301 
was present in 46.1% of the children with protracted forms (vs. 9.8% in healthy
controls; relative risk [RR]: 7.6; chi(2) = 33.3; P = 2 x 10(-9)). In
uncomplicated hepatitis, 45% developed anti-smooth muscle antibody (SMA)/actin
antibodies, but only 1 child had detectable antibodies after 3 months of
infection onset. In contrast, after 1 year, 69% of the patients suffering
protracted forms had titers of anti-SMA/actin antibodies that ranged between 1:40
and 1:160. Within their follow-up, 2 patients developed a Hashimoto's
thyroiditis, but the remaining patients showed no signs of developing autoimmune 
hepatitis. We conclude that the DRB1*1301 haplotype is strongly associated with
the protracted forms of HAV infection and suggest that the infection allows a
sustained release of liver self-antigens. However, other still-unknown
susceptibility genes are required for the full development of pediatric AH.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11391541 [PubMed - indexed for MEDLINE]

679: Am J Trop Med Hyg. 2000 Sep-Oct;63(3-4):189-91.

Association between seropositivity of antibodies against hepatitis a virus and
Helicobacter pylori.

Lin DB, Tsai TP, Yang CC, Wang HM, Nieh WT, Ling UP, Changlai SP, You SL, Ho MS, 
Chen CJ.

School of Medical Technology, and Graduate Institute of Medicine, Department of
Anatomy, Chung Shan Medical and Dental College, Taichung, Taiwan, Republic of
China.

Helicobacter pylori and hepatitis A virus (HAV) are documented to share common
transmission routes including fecal-oral. This study examined the association
between seropositivity of antibodies against H. pylori (anti-HP) and HAV
(anti-HAV) via a community-based survey of 40 randomly selected kindergartens in 
10 urban and 10 rural areas. Serum samples from 2,047 healthy preschool children 
and 104 teachers were screened for anti-HP by enzyme-linked immunosorbent assay, 
and for anti-HAV by microparticle enzyme immunoassay. In children, a low
prevalence of anti-HAV (0.44%) was found, in contrast to a high prevalence in
their teachers (78.8%); anti-HP seroprevalence was 6.4% for children and 30.8%
for teachers. Anti-HAV and anti-HP seropositivities were significantly associated
in teachers after adjustment for age, sex, and residential area through multiple 
logistic regression analysis (multivariate-adjusted odds ratio = 7.3; 95%
confidence interval [CI] = 1.4-36.8, P < 0.001). Our findings suggest that HAV
and H. pylori may have shared transmission routes in central Taiwan 15 years or
more ago, but not any recently.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11388513 [PubMed - indexed for MEDLINE]

680: J Obstet Gynecol Neonatal Nurs. 2001 May-Jun;30(3):316-23.

Sexually transmitted viral infections: epidemiology and treatment.

Thomas DJ.

Florida Atlantic University, College of Nursing, Boca Raton 33431-0991, USA.
dthomas@fau.edu

Human papillomavirus, herpes simplex virus, and both hepatitis A and B are some
of the most common sexually transmitted infections (STI) worldwide. They are
preventable, but unlike bacterial STIs the person may harbor the virus in her or 
his body for life with periodic recurrences of active infection. Viral STIs have 
long-term health consequences, some of which are serious and life threatening.
Nurses not only care for individuals who have a viral STI but also can provide
education for prevention.

Publication Types: 
    Review

PMID: 11383955 [PubMed - indexed for MEDLINE]

681: Saudi Med J. 2000 Oct;21(10):945-9.

Seroprevalence of hepatitis A virus markers in Eastern Saudi Arabia.

Fathalla SE, Al-Jama AA, Al-Sheikh IH, Islam SI.

Dammam Regional Labs & Blood Bank, PO Box 4103, Dammam 31491, Kingdom of Saudi
Arabia.

OBJECTIVE: To record and update the sero-epidemiological status of Hepatitis A
virus in Eastern Saudi Arabia. To investigate the main viral etiology of clinical
hepatitis in children and discuss the possibility of introducing a Hepatitis A
virus vaccine in this Province. METHODS: Examining serum specimens by Enzyme
Linkage Immuno-Sorbet Assay technique for these parameters: Immunoglobulin M
anti-hepatitis A virus, total immunoglobulin anti-hepatitis A virus, and in
selected cases we checked for hepatitis B surface antigen and anti-hepatitis C
virus. The study was carried out in the Virology Diagnostic Labs, of Dammam
Regional Laboratories & Blood Bank, Dammam. A total of 12,357 serum samples were 
collected from 5876 healthy children, 5798 healthy adults, and 683 from
clinically diagnosed hepatitis in children. The period of study was 12 years from
February 1987 to January 1999. RESULTS: Hepatitis A virus prevalence showed 3%
for pre-school age, 80% in older children and 93% in adults, while total
prevalence was 86%. Breaking down the prevalence among children showed 3% in the 
<6 years age group, 62% in the 6 - <8 years age group, 71% in the 8 - <10 years
age group, 83% in the 10 - <12 years age group and 93% in the 12 - <18 years age 
group. While the grand total among children was 78%. The prevalence of hepatitis 
viruses causing clinical hepatitis in children showed: 65% for hepatis A virus,
21% for hepatitis B virus, 7% for hepatitis C virus, 2% for double infection of
hepatitis B virus + hepatitis C virus and 5% for non A, non B, non C. CONCLUSION:
Hepatitis A virus infection starts dramatically high in school-age children, and 
then rises gradually with an increase in age. This reflects that our region is of
pattern I class. There is no difference in the prevalence due to seasons of year,
climate or sex. Hepatitis A virus is the leading cause of clinical hepatitis in
children, followed by hepatitis B virus and hepatitis C virus. There is a
possibility of starting to introduce hepatitis A virus vaccine among pre-school
age children, as well as among hepatitis A virus negative adults that live in a
higher socioeconomic environment within the country, which can be considered as
islands of pattern II among pattern I areas.

PMID: 11369959 [PubMed - indexed for MEDLINE]

682: J Med Virol. 2001 Jun;64(2):104-8.

Change in hepatitis A virus seroepidemiology in southern Taiwan: a large
percentage of the population lack protective antibody.

Wang SM, Liu CC, Huang YS, Yang YJ, Lei HY.

Department of Emergency Medicine, National Cheng Kung University Hospital, 138
Sheng Li Road, Tainan, Taiwan.

Hepatitis A, the predominant reported etiologic form of viral hepatitis in
Taiwan, continues to be a disease primarily of children and young adults. A
seroepidemiologic study was performed to assess the seroprevalence of hepatitis A
(HAV) antibodies in the southern Taiwan general population in 1998 and is
compared with results of a similar study in 1992. A total of 948 subjects (477
male and 471 female) with ages ranging from 0.3 to 63 years were stratified into 
14 age-specific groups. The presence of anti-HAV antibodies was detected using a 
commercially available radioimmunoassay. Fifteen percent of the subjects were
positive for anti-HAV antibodies, which is lower than that in 1992 (P < 0.001).
Seroprevalences were 14.1% for males and 22.6% for females (P = 0.006). The
pattern of anti-HAV seroprevalence was distinguishable from that found in 1992;
minimum seroconversion occurred at ages ranging from 1 to 30 years. Prevalence of
seropositive subjects decreased markedly for the < 1, 13-15, 16-19, 20-24, 25-29,
and 30-39 year age groups in comparing 1998 with 1992. The current study
demonstrates a continuing decline in the prevalence of HAV among children,
adolescents, and young adults. The findings can be ascribed to the improvement of
socioeconomic status and modernization of environmental sanitation. As a
consequence of this changing trend of endemicity and the resulting lack hepatitis
A antibodies among the general population in Taiwan, the risk of sudden major
outbreaks is increased because of increasing international travel and
immigration, particularly during and after natural disasters. HAV vaccination
will be important for the prevention and control of HAV outbreaks in the
community. Copyright 2001 Wiley-Liss, Inc.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11360241 [PubMed - indexed for MEDLINE]

683: J Med Virol. 2001 Jun;64(2):96-103.

Genetic relatedness of Cuban HAV wild-type isolates.

Diaz BI, Sariol CA, Normann A, Rodríguez L, Flehmig B.

Department of Virology and Epidemiology of Virus Diseases, Hygiene Institute,
University of Tuebingen, Germany. belkis.diaz-mendiondo@med.uni-tuebingen.de

Knowledge of the nucleotide sequence in the region of the putative VP1/2A
junction of the Hepatitis A virus (HAV) genome has enabled differentiation of HAV
strains and their classification into seven genotypes, in some of which
sub-genotypes A and B can be defined. A 168 base segment encompassing the
putative VP1/2A junction of 27 clinical wild-type isolates of HAV from Cuba was
amplified by reverse transcriptase-polymerase chain reaction and then sequenced. 
The Cuban isolates are clustered within sub-genotype IA. A single amino acid
substitution, which does not correspond with any of the reported changes for
other strains, was observed. A new sub-genotype variant is therefore postulated. 
This study provides new data on the genetic relatedness of HAVs from Cuba and on 
the distribution of sub-genotype IA in the Caribbean area. Copyright 2001
Wiley-Liss, Inc.

Publication Types: 
    Comparative Study

PMID: 11360240 [PubMed - indexed for MEDLINE]

684: J Gastroenterol Hepatol. 2001 May;16(5):519-24.

Molecular epidemiology of hepatitis A virus in Korea.

Byun KS, Kim JH, Song KJ, Baek LJ, Song JW, Park SH, Kwon OS, Yeon JE, Kim JS,
Bak YT, Lee CH.

Department of Gastroenterology and Hepatology, Korea University Guro Hospital,
Seoul.

BACKGROUND: The prevalence of antibodies for hepatitis A virus (anti-HAV) in
adolescents and young adults has decreased remarkably following the economic
growth in Korea. As a result, this age group has a high risk for HAV infection
paradoxically, and over 1500 cases of clinically overt hepatitis A occurred in
1998. Human isolates of hepatitis A virus (HAV) are categorized within four
genotypes (I, II, III, and VII). In some geographic regions, closely related
isolates cluster, suggesting endemic spread of the virus, while in other regions 
multiple genotypes circulate. Virtually no data are available with regard to the 
genetic relatedness of Korean strains of HAV. METHODS AND RESULTS: A 168 base
pair segment encompassing the putative VP1/2A junction of the HAV genome was
amplified by RT-PCR and sequenced in sera of 18 Korean patients with a sporadic
form of acute hepatitis A. Pairwise comparisons of the nucleic acid and amino
acid sequences of 18 Korean isolates with one another revealed that the Korean
isolates showed > 94.6% and > 96.4% identity, respectively. All of the 18 Korean 
isolates clustered within genotype IA, irrespective of the geographic locations
and the time that hepatitis occurred. Unique amino acid sequence changes that had
never been reported in genotype IA were found in nine of the 18 isolates. These
changes were Gln-->Ser and Lys-->Arg in 2A-19 and 2A-10 amino acid positions.
CONCLUSION: The presence of single genotype and unique mutations may be related
with the circulation of endemic HAV over a long period of time in Korea.

PMID: 11350547 [PubMed - indexed for MEDLINE]

685: Eur J Clin Microbiol Infect Dis. 2001 Mar;20(3):185-7.

Control of a community-wide outbreak of hepatitis A by mass vaccination with
inactivated hepatitis A vaccine.

Zamir C, Rishpon S, Zamir D, Leventhal A, Rimon N, Ben-Porath E.

Jerusalem District Health Office, Ministry of Health, Israel.
hdrzamir@matat.health.gov.il

The epidemiology and control of hepatitis A virus was investigated during an
outbreak of hepatitis A in a village in Israel. Postexposure administration of
immune globulin to contacts was ineffective in controlling the outbreak. However,
within 2 weeks of starting a mass immunization campaign with hepatitis A vaccine,
the incidence of hepatitis A declined dramatically; the last case occurred 6
weeks after the immunization program began. The study demonstrated that while
postexposure administration of immune globulin may diminish but not entirely
arrest transmission of hepatitis A virus, active hepatitis A vaccination is a
safe and effective intervention that can be used safely in hepatitis A virus
antibody-positive children.

PMID: 11347668 [PubMed - indexed for MEDLINE]

686: Med J Aust. 2001 Apr 2;174(7):338-41.

Comment in:
    Med J Aust. 2001 Nov 5;175(9):502-3.

Hepatitis A epidemiology in Australia: national seroprevalence and notifications.

Amin J, Gilbert GL, Escott RG, Heath TC, Burgess MA.

National Centre for Immunisation Research and Surveillance of Vaccine Preventable
Diseases, Children's Hospital at Westmead and University of Sydney, NSW.

OBJECTIVES: To determine hepatitis A seroprevalence and notification rates in
Australia in order to inform vaccination policy. DESIGN: Seroprevalence was
determined by cross-sectional survey of opportunistically collected sera;
notifications were extracted from the National Notifiable Diseases Surveillance
System. PARTICIPANTS: 3,043 serum samples collected in 1998 were obtained from 46
laboratories around Australia. Sample size in each age group was based on
expected seroprevalence, and States and Territories were sampled proportionally
to their population size. Males and females were equally represented.
Notifications were extracted for cases with onset between 1 January 1991 and 31
December 1998. MAIN OUTCOME MEASURES: Seroprevalence and notifications were
analysed by age, sex and State/Territory. RESULTS: 41.1% of serum samples were
seropositive for hepatitis A (95% CI, 39.4%-42.9%) (population-weighted
seroprevalence, 38.3%). Seroprevalence was significantly associated with
increasing age (P<0.001), but did not differ between the sexes (male:female
ratio, 1.04:1; 95% CI, 0.95-1.14). However, significantly more notifications were
recorded for males than females (male:female ratio, 1.65:1; 95% CI, 1.60-1.70).
The Northern Territory had the highest seroprevalence (68.8%; 95% CI,
52.7%-84.8%) and annual notification rates (48.7 per 100,000 population; 95% CI, 
45.0-52.4 per 100,000). CONCLUSIONS: These data show that about half the
Australian population has not been exposed to hepatitis A and is therefore
susceptible to infection. However, any decision on national routine childhood
hepatitis A vaccination requires a cost-benefit analysis. Routine vaccination of 
high-incidence communities remains controversial.

PMID: 11346106 [PubMed - indexed for MEDLINE]

687: Indian J Pathol Microbiol. 2000 Oct;43(4):433-6.

Prevalence of enterically transmitted hepatitis viruses in patients attending a
tertiary--care hospital in south India.

Radhakrishnan S, Raghuraman S, Abraham P, Kurian G, Chandy G, Sridharan G.

Departments of Clinical Virology and Gastrointestinal Sciences, Christian Medical
College & Hospital, Vellore.

The prevalance of enterically transmitted hepatitis viruses, namely, hepatitis A 
virus (HAV) and hepatitis E virus (HEV) were studied in 404 patients with acute
hepatitis attending a tertiary-care hospital in south India. Presence of current 
HAV/HEV infection was ascertained by the demonstration of IgM antibodies. In 381 
patients tested for both agents, HAV IgM was present in 51(13.3%) and HEV IgM
present in 66(17.3%). There was dual infection in 3 males (0.8%). HEV infection
was seen mostly in older children and adults with only 5.5% occurring in children
< 12 years of age. HAV infection was commonly seen to occur in < 12 years of age 
group (52.7%). One hundred and twenty-six patients were from the Vellore region, 
among whom HAV and/or HEV aetiology was observed in 28.5%. In this region there
did not appear to be any correlation between occurrence of acute hepatitis due to
these viruses and rainfall or environmental temperature. Acute hepatitis due to
enteric hepatitis viruses was seen throughout the year.

PMID: 11344607 [PubMed - indexed for MEDLINE]

688: Indian J Pathol Microbiol. 2000 Oct;43(4):409-15.

Electron microscopy of buffalo green monkey kidney cells persistently infected
with hepatitis A virus and immunolocalization of HAV antigens.

Basu A, Gangodkar SV, Joshi MS, Chitambar SD.

National Institute of Virology, 20A, Dr. Ambedkar Road, Pune.

Studies were carried out to analyse the ultrastructural changes and the
distribution of hepatitis A virus (HAV)/antigens at subcellular level in buffalo 
green monkey kidney (BGMK) cells persistently infected with HM-175 strain of HAV.
HAV infected BGMK cells showed distinct abnormalities in the endoplasmic
reticulum and cytoplasmic membrane as compared to uninfected cells. The
abnormalities were characterized by wavy arrays, structures like myelin, annulate
lamellae, cytoplasmic inclusion bodies and vesicles. The wavy arrays within the
cytoplasm of the host cells appeared to represent degenerating membranes. A
complex myelin like body was found in close association with a group of virus
like particles. Annulate lamellae like structures involving single paired
membrane were detected infrequently whereas the cytoplasmic vesicles were
numerous in these cells. An indirect immunogold technique was utilized to
localize the HAV antigenin infected cells. A high density immunogold label for
HIV like particles was predominantly detected in cytoplasmic vesicles. These
results suggest a strong association of membrane substructure in vesicle forms
with the compartmentalized replication of HAV within persistently infected host
cells.

PMID: 11344603 [PubMed - indexed for MEDLINE]

689: J Pediatr. 2001 May;138(5):705-9.

A prevalence study of hepatitis A virus infection in a migrant community: Is
hepatitis A vaccine indicated?

Dentinger CM, Heinrich NL, Bell BP, Fox LM, Katz DJ, Culver DH, Shapiro CN.

Hepatitis Branch, Division of Viral and Rickettsial Diseases, National Center for
Infectious Diseases, Centers for Disease Control and Prevention, Atlanta,
Georgia, USA.

BACKGROUND: The Advisory Committee on Immunization Practices recommends routine
hepatitis A vaccination of children living in communities with high rates of
hepatitis A. Rates among children living in migrant farm worker families are
unknown. METHODS: Participants recruited from the 1243 migrant children aged 2 to
18 years in Okeechobee County, Florida, were administered a questionnaire. A
blood sample was taken for testing for antibodies to hepatitis A virus
(anti-HAV), and hepatitis A vaccine was administered. RESULTS: Of 244 (20%)
participating children, 125 (51%) were anti-HAV-positive. Seropositivity
increased with age from 34% (2- to 5-year-olds) to 81% (>/=14-year-olds) (P
<.0001). In multivariate analysis, age (odds ratio [OR] = 1.2/year; 95% CI = 1.1 
to 1.3), having a Mexican-born father (OR = 12.2; 95% CI = 2.2 to 227.9), and age
on moving to the United States (OR = 1.3/year; 95% CI = 1.0 to 1.6) were
independently associated with anti-HAV positivity. Among US-born children aged 2 
to 5 years who had never left the United States, 33% were anti-HAV-positive.
CONCLUSIONS: Anti-HAV prevalence among migrant children in Okeechobee County,
including the youngest US-born children, is high, indicating ongoing transmission
of HAV. Children in this and other US migrant communities may benefit from
hepatitis A vaccination.

PMID: 11343047 [PubMed - indexed for MEDLINE]

690: Tex Med. 2001 Mar;97(3):68-72.

Trends in the incidence of hepatitis A in Texas, 1986 through 1997.

Brender JD, Vanegdom MJ, Nuno O.

Department of Health Services and Research, Southwest Texas State University, San
Marcos, Tex., 601 University Dr, San Marcos, TX 78666, USA.

Hepatitis A is one of the most common infections reported in Texas. This study
examined the trends in incidence of hepatitis A in Texas for the years from 1986 
through 1997. Demographic and clinical data of reported cases were obtained from 
the Texas Department of Health. Population estimates were obtained from Epigram. 
Rates were calculated per 100,000 population. For the 1986-1997 period, 33,833
cases of acute hepatitis A were reported. Rates varied considerably by ethnicity 
and race: Hispanics had the highest average annual rate (32.2 per 100,000),
followed by non-Hispanic whites (8.2 per 100,000) and African Americans (6.0 per 
100,000). The rate for Hispanics was more than two times higher than the rates
for non-Hispanic whites and African Americans in all 11 public health regions in 
Texas. Children aged 5 through 9 years had the highest rates of hepatitis A. The 
3-month period from August through October had the largest reported number of
onsets of hepatitis A (P < .01).

PMID: 11320965 [PubMed - indexed for MEDLINE]

691: J Clin Gastroenterol. 2001 May-Jun;32(5):453-4.

Familial cluster of fulminant hepatitis A infection.

Durst RY, Goldsmidt N, Namestnick J, Safadi R, Ilan Y.

Internal Medicine Division, Hadassah Medical School, Jerusalem, Israel.
Durst@cc.huji.ac.il

Hepatitis A virus is a common cause of a self-limited liver disease. Fulminant
hepatitis is a rare complication of acute hepatitis A infection. We report a
small epidemic of three consecutive fulminant hepatitis A infections in three
previously healthy siblings. This is the first report of a cluster of fulminant
hepatitis A.

Publication Types: 
    Case Reports

PMID: 11319325 [PubMed - indexed for MEDLINE]

692: Asian Pac J Allergy Immunol. 2000 Dec;18(4):249-53.

Increasing susceptibility to HAV among members of the young generation in
Thailand.

Poovorawan Y, Theamboonlers A, Sinlaparatsamee S, Chaiear K, Siraprapasiri T,
Khwanjaipanich S, Owatanapanich S, Hirsch P.

Department of Pediatrics, Faculty of Medicine, Chulalongkorn University &
Hospital, Bangkok, Thailand.

The prevalence of antibodies to hepatitis A virus was studied in 961 children and
adolescents, randomly selected from five different provinces in Thailand
(Chonburi, Lopburi, Udonthani, Nakhon Si Thammarat and Lopburi). The highest
prevalence was found in Nakhon Si Thammarat, with 32.1 percent of those aged
10-14 years and 57.1 percent of those aged 15-18 years showing evidence of
protective immunity. However, this high rate could be explained by an outbreak of
hepatitis A in 1992. In the remaining four provinces, the pattern was typically
age-related in that all individuals showed between zero and 13 percent antibody
prevalence until reaching the 15-to-18-year age group where it increased to
between 5.6 and 22.7 percent. The overall sero-prevalence among all age groups
was 7.9 percent. Thus, the majority of the younger generation is susceptible to
hepatitis A virus infection thereby enhancing the impact, should an outbreak
occur. Preventive measures that might be taken are education aimed at better
hygiene and sanitation, as well as vaccination of susceptible individuals within 
high-risk populations.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11316047 [PubMed - indexed for MEDLINE]

693: Pharmacoeconomics. 2001;19(3):281-91.

Cost-benefit analysis of active vaccination campaigns against hepatitis A among
daycare centre personnel in Israel.

Chodick G, Lerman Y, Peled T, Aloni H, Ashkenazi S.

Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
chodick@post.tau.ac.il

OBJECTIVE: To evaluate, in economic terms, active vaccination campaigns against
hepatitis A in comparison with the use of nonspecific immune globulin for the
prevention of the disease among daycare centre employees in Israel. SETTING:
Hypothetical analysis of the costs and benefits related to vaccination campaigns 
of workers currently employed in daycare centres in Israel. METHODS: A
cost-benefit analysis was performed, comparing mass and selective active
vaccination strategies for the daycare centre working force. Direct and indirect 
costs of diagnosis, treatment and immunisation as well as productivity loss were 
considered. A Markov-based model was developed using data from previous
epidemiological studies and literature. RESULTS: The benefit-to-cost ratios of
selective and mass active vaccination strategies were 1.50 [net present value
(NPV) $US606 396] and 0.04 (NPV-$US2.36 million), respectively (2000 values).
CONCLUSION: Under these study assumptions, the practice of administering
hepatitis A active vaccine to serologically proven non-immune daycare centre
workers has a cost-benefit justification, and should be widely considered in
countries with a similar hepatitis A epidemiology to that in this study.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, Non-P.H.S.

PMID: 11303416 [PubMed - indexed for MEDLINE]

694: J Addict Dis. 2001;20(1):9-17.

Comment in:
    J Addict Dis. 2001;20(1):1-7.

Hepatitis C, B, D, and A: contrasting features and liver function abnormalities
in heroin addicts.

Tennant F.

Veract, Inc., West Covina, CA 91790, USA.

Over 90% of intravenous heroin addicts (IVHAs) carry the hepatitis C virus (HCV).
The other hepatitis viruses, A, B, D, and G are relatively unimportant in IVHAs
compared to HCV although active hepatitis B may demonstrate a chronic,
degenerative course identical to that of HCV. The clinical course of HCV and
active hepatitis B may span three or more decades. It is helpful to classify
patients as in the active, cirrhosis, or liver failure stages. Only in the
active, early stage are the liver enzymes, ALT and AST, likely to be elevated. It
is this stage that will most likely respond to antiviral therapy. HCV has so many
extra-hepatic manifestations including immune suppression, collagen diseases, and
possibly lymphoma and leukemia that the disease is best termed HCV syndrome
rather than simple hepatitis.

PMID: 11286434 [PubMed - indexed for MEDLINE]

695: Vaccine. 2001 Apr 6;19(20-22):2878-83.

Detection of antibodies to HAV 3C proteinase in experimentally infected
chimpanzees and in naturally infected children.

Kabrane-Lazizi Y, Emerson SU, Herzog C, Purcell RH.

Hepatitis Viruses and Molecular Hepatitis Sections, Laboratory of Infectious
Diseases, National Institute of Allergy and Infectious Diseases, National
Institutes of Health, Bethesda, MD 20892, USA.

Commercial assays for the diagnosis of hepatitis A detect antibody to hepatitis A
virus (anti-HAV), but they cannot discriminate between antibody resulting from
infection and antibody induced by inactivated vaccine. With the licensing and
increasing use of inactivated hepatitis A vaccines, there is a need for a test to
distinguish between infection and vaccination. Since antibodies to viral
non-structural proteins are elicited by infection but not by vaccination with
inactivated vaccine, we developed and evaluated a test for such antibodies. The
antibody response to the non-structural 3C proteinase (anti-3C) of virus HAV was 
studied by ELISA in chimpanzees experimentally infected with virulent (wild type)
or with attenuated HAV strains and in children who received inactivated HAV
vaccine or placebo during a vaccination trial in Nicaragua. Anti-3C was detected 
in 89% of 18 chimpanzees infected with wild-type HAV strains and 27% of 26
chimpanzees infected with attenuated HAV strains. There was a direct correlation 
between severity of hepatitis and magnitude of the anti-3C response. In the
vaccine trial, anti-3C was detected only in children who were infected with HAV
during the study; IgG anti-3C persisted for at least 15 months after infection in
one child. Vaccinated and uninfected children remained negative for anti-3C. The 
anti-3C response can be regarded as an indicator of viral replication. Its
detection should be useful for distinguishing between antibody acquired in
response to HAV infection and antibody induced by immunization with inactivated
vaccine.

PMID: 11282198 [PubMed - indexed for MEDLINE]

696: J Infect Dis. 2001 Apr 15;183(8):1273-6. Epub 2001 Mar 26.

An outbreak of hepatitis A associated with green onions.

Dentinger CM, Bower WA, Nainan OV, Cotter SM, Myers G, Dubusky LM, Fowler S,
Salehi ED, Bell BP.

Hepatitis Branch, Centers for Disease Control and Prevention, 1600 Clifton Road, 
MS G-37, Atlanta, GA 30333, USA. cgd1@cdc.gov

Forty-three cases of serologically confirmed hepatitis A occurred among
individuals who ate at restaurant A in Ohio in 1998. Serum samples from all
restaurant A employees who worked during the exposure period were negative for
IgM antibodies to hepatitis A virus (HAV). A matched case-control study
determined that foods containing green onions, which were eaten by 38 (95%) of 40
case patients compared with 30 (50%) of 60 control subjects, were associated with
illness (matched odds ratio, 12.7; 95% confidence interval, 2.6-60.8). Genetic
sequences of viral isolates from 14 case patients were identical to each other
and to those of viral isolates from 3 patients with cases of hepatitis A acquired
in Mexico. Although the implicated green onions, which could have come from one
of 2 Mexican farms or from a Californian farm, were widely distributed, no
additional green onion-associated cases were detected. More sensitive methods are
needed to detect foodborne hepatitis A. A better understanding of how HAV might
contaminate raw produce would aid in developing prevention strategies.

Publication Types: 
    Comparative Study

PMID: 11262211 [PubMed - indexed for MEDLINE]

697: Dig Dis Sci. 2000 Dec;45(12):2422-7.

PCR-SSCP analysis of 5'-nontranslated region of hepatitis A viral RNA: comparison
with clinicopathological features of hepatitis A.

Fujiwara K, Yokosuka O, Ehata T, Imazeki F, Saisho H.

First Department of Internal Medicine, Chiba University School of Medicine,
Japan.

The recent development of the sensitive reverse transcription-polymerase chain
reaction (RT-PCR) method allowed us to detect the presence of hepatitis A virus
(HAV) RNA in sera from hepatitis A patients. To determine whether differences in 
HAV are related to the wide range of clinical severity, we used PCR-single strand
conformation polymorphism (SSCP) to analyze the amplified product of the
5'-nontranslated region (5'NTR), where relatively homologous sequences are
reported and the internal ribosomal entry site is considered to exist, from these
various levels of hepatitis A. Twenty-seven patients admitted to Chiba University
Hospital (between 1988 and 1997) were examined for HAV RNA in their sera by
RT-PCR with primers located at 5'NTR of HAV RNA. The nucleotide (nt) sequence of 
a central part (nt 277-551) of 5'NTR was amplified and the product was examined
by PCR-SSCP. HAV RNA was detected in all 27 hepatitis A patients examined: in 3
with fulminant hepatitis, 2 with severe acute hepatitis, and 22 with self-limited
acute hepatitits. The amplified sequence revealed by PCR-SSCP showed that samples
from fulminant and severe acute hepatitis patients had similar mobility in the
gel, whereas that from acute hepatitis patients demonstrated a considerable
variety in mobility patterns. From the analysis of the amplified product of 5'NTR
of HAV, the bands are likely to be similar in the more severe forms of hepatitis 
A compared to those from uncomplicated self-limited acute hepatitis.

Publication Types: 
    Comparative Study

PMID: 11258569 [PubMed - indexed for MEDLINE]

698: Vaccine. 2001 Mar 21;19(17-19):2404-6.

Vaccination policy against hepatitis A in Italy.

Stroffolini T, Mele A, Sagliocca L.

Laboratory of Epidemiology - I.S.S., Viale Regina Elena, 299, 00161, Rome, Italy.

In Italy, improved sanitation and living conditions have led to a decline in the 
rate of hepatitis A infection among children generating an increasing proportion 
of adults susceptible to this virus. Shellfish consumption is a major source of
infection while person to person transmission is important in the spread of
infection and in the maintenance of outbreaks. Thus prevention of secondary HAV
infection is a crucial point. A randomised controlled trial of hepatitis A
vaccine in household contacts of people with sporadic HAV infection in Italy has 
shown a protective efficacy of 82% (CI 20-96%). The two secondary infections in
the vaccine group were symptomless, suggesting that the disease expression may be
weaker in vaccinated subjects.

PMID: 11257369 [PubMed - indexed for MEDLINE]

699: J Infect. 2001 Jan;42(1):57-60.

Infection of hepatitis A virus in Japanese haemophiliacs.

Hayashi K, Fukuda Y, Nakano I, Katano Y, Nagano K, Yokozaki S, Hayakawa T, Toyoda
H, Takamatsu J.

Second Department of Internal Medicine, Nagoya University School of Medicine,
Nagoya, Japan.

OBJECTIVES: Outbreaks of hepatitis A virus (HAV) infection in haemophiliacs have 
been reported from many countries. The aim of this study was to determine the
prevalence of hepatitis A virus antibody (HAVAb) in Japanese haemophiliacs.
METHODS: Sixty-seven male haemophiliacs were recruited for this study of HAV
infection. We also compared the rate of HAV infection with that of human
immunodeficiency virus (HIV), hepatitis C virus (HCV), and hepatitis G virus
(HGV). RESULTS: Fifteen of 67 haemophiliacs (22.4%) were positive for HAVAb.
Prevalence of HAVAb was significantly higher in haemophiliacs than in Japanese
normal subjects previously reported (P= 0.0001). Age, alanine aminotransferase
(ALT), aspartate aminotransferase (AST), total bilirubin and prevalence of HIV,
HCV, and HGV were not statistically different between HAVAb positive and HAVAb
negative haemophiliacs. We suggest that the use of clotting factor concentrates
is closely associated with HAV infection, but HAV infection does not have an
effect on clinical course. CONCLUSIONS: Administration of clotting factor
concentrates may increase risk of HAV infection in haemophiliacs. Copyright 2001 
The British Infection Society.

Publication Types: 
    Comparative Study

PMID: 11243755 [PubMed - indexed for MEDLINE]

700: J Epidemiol Community Health. 2001 Apr;55(4):251-6.

Hepatitis A vaccination during an outbreak among gay men in Montréal, Canada,
1995-1997.

Allard R, Beauchemin J, Bédard L, Dion R, Tremblay M, Carsley J.

Unité Maladies infectieuses, Direction de la santé publique de Montréal-Centre,
Canada.

STUDY OBJECTIVE: To evaluate an intervention designed to curtail an outbreak of
hepatitis A among gay men, especially the young and sexually active, by promoting
their free vaccination. DESIGN: The study analysed routine passive surveillance
data, carried out questionnaire and serological surveys of vaccinees, and surveys
among the target population in non-clinical venues. SETTING AND INTERVENTION: 15 
000 free doses of hepatitis A vaccine were made available through clinics with
large gay clienteles, or at gay events, and advertised by various means, in
Montréal, Canada, from August 1996 to November 1997. Simultaneous vaccination
against hepatitis B (always free for gay men) was also encouraged. PARTICIPANTS: 
Information was obtained from persons with the disease during the epidemic
period, a sample of men requesting vaccination, and five community samples of gay
men. MAIN RESULTS: The outbreak involved 376 gay men and the vaccine was
distributed to approximately 10 000. Vaccinees were older than cases, but had
many sex partners and comprised more food handlers. Special vaccination clinics
at gay events were well attended but did not reach more high risk men than
regular medical venues. A self reported vaccine coverage of 49% was achieved, but
26% of vaccinees already had anti-HAV antibodies. Disease incidence declined
rapidly during the campaign. CONCLUSIONS: The intervention nearly tripled self
reported hepatitis A vaccine coverage but its late start precludes proving that
it caused the subsequent drop in incidence. However, it also increased hepatitis 
B vaccination and it is believed it improved links between gay men, public
health, clinicians and community groups.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11238580 [PubMed - indexed for MEDLINE]

701: Scand J Infect Dis. 2001;33(2):121-5.

Infection with hepatitis A and TT viruses and socioeconomic status in Rio de
Janeiro, Brazil.

Saback FL, Palmer TE, Sabino RR, Carvalho SM, Amorim LM, Gaspar AM, Oliveira ML, 
Yoshida CF, Niel C.

Department of Virology, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.

The prevalence of antibodies directed against the enterically transmitted
hepatitis A virus (HAV) was measured in 2 groups of people living in Rio de
Janeiro, Brazil. Of 1,056 health care workers (HCWs), 778 (73.7%) were anti-HAV
positive. A high prevalence of anti-HAV antibodies (85.7%) was also found among
274 voluntary blood donors (BDs). TT virus (TTV) is a DNA virus that has been
found in the sera of patients with post-transfusion hepatitis of unknown
etiology. Occurrence of virus shedding suggests that the fecal-oral route may be 
an important mode of TTV transmission, particularly in the developing world. The 
presence of TTV DNA was analyzed by PCR in the sera of 191 HCWs and 151 BDs. TTV 
was detected in 65.4% of HCWs and 79.5% of BDs. In both groups, a family income
of < US$400 per month and a level of education of < 11 y of schooling were found 
to be risk factors for HAV infection. Furthermore, a low family income was
associated with TTV viremia in the HCW group. However, the presence of TTV DNA
was associated with neither low level of education nor anti-HAV positivity.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11233846 [PubMed - indexed for MEDLINE]

702: Clin Liver Dis. 2000 Feb;4(1):47-71, vi.

Viral hepatitis A, B, and C.

Regev A, Schiff ER.

Center for Liver Diseases, Jackson Medical Towers, Suite 1101, 1500NW 12th
Avenue, Miami, Florida, 33136 USA.

Mankind probably has known viral hepatitis for many centuries; however, the major
and most dramatic developments in our knowledge of these diseases have taken
place during the second half of the 20th century. During this relatively short
period of time, the infectious nature of hepatitis A, B, and C has been proven,
leading to their identification and description. The advent of serologic markers 
has provided the means for establishing the diagnosis. Epidemiologic studies have
provided important information that led to exciting achievements in detection and
prevention of transmission. Molecular biology studies and cell culture techniques
have established our knowledge of the viral genomes, and led to the development
of specific vaccines for hepatitis A and B. Anti-viral therapy has been developed
and aggressive combination therapy has emerged as a promising strategy for
chronic hepatitis B and C. This article reviews some of the main fields of
progress and achievement related to viral hepatitis A, B, and C in the 20th
century.

Publication Types: 
    Review

PMID: 11232191 [PubMed - indexed for MEDLINE]

703: Vaccine. 2001 Feb 28;19(15-16):2138-45.

The economics of vaccinating restaurant workers against hepatitis A.

Meltzer MI, Shapiro CN, Mast EE, Arcari C.

Office of the Director, National Center for Infectious Diseases, Centers for
Disease Control and Prevention, Atlanta, GA 30333, USA. qzm4@cdc.gov

The economics of vaccinating restaurant workers against hepatitis A were studied 
using Monte Carlo simulation models, one with a restaurant-owner perspective, and
one with a societal perspective. The restaurant model allowed for a different
size, number of employees and employee turnover rate. Benefits were the avoidance
of loss of business (including the possibility of bankruptcy) after publicity
linking the restaurant to an outbreak associated with a case of hepatitis A in a 
food handler. Additional benefits in the societal model included reductions in
costs of food handler-associated cases of hepatitis A. The outcome used was Net
Present Value (NPV), allowing comparison between models. Regardless of the cost
of vaccination ($50-140/employee), for a restauranteur to ensure that all
employees were vaccinated at all times substantial costs were involved (i.e.
negative NPV). Even a 75% probability of bankruptcy still resulted in negative
NPVs at the 95th percentiles. For society, vaccination was only cost-saving (i.e.
positive NPV) if done only during epidemics and if it cost < $20/employee.
Vaccinating restaurant employees is unlikely to be economical from either the
restaurant owner or the societal perspective, even during hepatitis A epidemics.

PMID: 11228386 [PubMed - indexed for MEDLINE]

704: J Hepatol. 2001 Jan;34(1):92-9.

Cost-benefit analysis of a nationwide infant immunization programme against
hepatitis A in an area of intermediate endemicity.

Ginsber GM, Slater PE, Shouval D.

Medical Technology Assessment Sector, Ministry of Health, Jerusalem, Israel.
mttgary@matat.health.gov.il

BACKGROUND/AIMS: The availability of safe and effective Hepatitis A vaccines
prompts an evaluation of a nationwide infant vaccination campaign to supplement
strategies aimed at high-risk groups such as travellers and military personnel.
METHODS: A spreadsheet model was used to estimate costs and benefits of a
nationwide infant immunization programme against Hepatitis A for the period from 
1997-2014 in Israel. RESULTS: Immunizing all one year olds in Israel from
1997-2014 would for a cost of $32.0 million to the health services and $42.1
million to society (including $10.1 million lost work and transport costs),
reduce the number of cases of Hepatitis A during the next 45 years from 181,000
to 47,000. This would save $57.5 million in health service resources alone, $32.0
million in averted work absences and transport costs in addition to a further
$17.0 million in averted premature mortality costs. The health service, resource 
and societal benefit:cost ratios are 1.80:1, 2.13:1 and 2.54:1, respectively.
CONCLUSIONS: The recent adoption of a nationwide infant HAV immunisation policy
in Israel is both medically and economically justifiable.

PMID: 11211913 [PubMed - indexed for MEDLINE]

705: J Gastroenterol Hepatol. 2001 Jan;16(1):112-4.

Lupus-like syndrome with submassive hepatic necrosis associated with hepatitis A.

Segev A, Hadari R, Zehavi T, Schneider M, Hershkoviz R, Mekori YA.

Department of Internal Medicine B, Meir Hospital, Kfar-Saba, Israel.
amitse@inter.net.il

Hepatitis A is a common self-limited liver disease. However, 15% of patients may 
have some complications. Autoimmune hepatitis that is triggered by viral
hepatitis has been reported. We hereby describe an unrecognized association of
hepatitis A with a full blown lupus-like syndrome manifested by the appearance of
arthralgia, exudative pleural effusion with the presence of lupus erythematosus
cells and autoantibodies. All these findings disappeared after a short course of 
steroid treatment. The case is presented and the literature is reviewed.

Publication Types: 
    Case Reports

PMID: 11206308 [PubMed - indexed for MEDLINE]

706: J Clin Gastroenterol. 2001 Feb;32(2):179-80.

A pregnant woman with hepatitis A and Guillain-Barré.

Breuer GS, Morali G, Finkelstein Y, Halevy J.

Department of Medicine, Shaare Zedek Medical Center, Hadassah Medical School,
Jerusalem, Israel. gbreuer@szmc.org.il

Guillain-Barré syndrome (GBS) is often preceded by an infectious disease. A case 
of GBS after hepatitis A in a pregnant woman is described. The patient was
treated with intravenous immunoglobulin and had full recovery with no neurologic 
sequelae. She gave birth in term to a healthy baby. This is the first reported
case in the English literature of a triple condition of hepatitis A, GBS, and
pregnancy.

Publication Types: 
    Case Reports

PMID: 11205660 [PubMed - indexed for MEDLINE]

707: Aust N Z J Med. 2000 Dec;30(6):668-74.

A serological re-evaluation of acute non-A non-B hepatitis from the early 1970s.

Binotto E, Boughton CR, Vollmer-Conna U, Hawkes R, Robertson P, Whybin R, Duffy
Y, Lloyd AR.

Department of Microbiology and Infectious Diseases, Liverpool Hospital, Sydney,
NSW.

BACKGROUND: The epidemiology and natural history of recently discovered viruses, 
which may be responsible for cases of seronegative infectious hepatitis, are
currently being investigated. Retrospective studies of stored sera can provide a 
historical perspective of these infections. AIMS: To re-evaluate the serological,
demographic and clinical characteristics of patients hospitalised in the early
1970s with acute hepatitis. METHODS: The stored sera of 57 patients hospitalised 
between 1971 and 1974 with acute hepatitis, designated at that time as non-A
non-B (NANB) hepatitis, were re-tested using commercially available enzyme-linked
immunosorbent assays (ELISAs) for the presence of anti-hepatitis A virus (HAV)
IgM, hepatitis B surface antigen (HBsAg), anti-hepatitis C virus (HCV) IgG, and
anti-hepatitis E virus (HEV) IgG. Stored sera from a group of 57 patients
concurrently hospitalised for other conditions were also tested. Detailed records
of the original epidemiological interviews were examined to compare patient
demographics, risk factors for infectious hepatitis and clinical data for the
NANB hepatitis group and an original control group of 604 hospitalised patients. 
RESULTS: Serum from 15 of the 57 (26%) previously designated NANB hepatitis cases
had elevated anti-HAV IgM and are likely to represent missed cases of hepatitis
A. Thirteen (23%) of cases previously designated as NANB hepatitis had positive
hepatitis C antibody tests. These patients were younger and significantly more
likely to have used intravenous drugs than control patients. Three NANB hepatitis
and two hospital control patients were anti-HEV IgG antibody positive. All of
these individuals were born in, or had travelled to, developing countries. Serum 
from 27 (47%) of the NANB hepatitis patients were negative on all tests. These
hepatitis non-A-E cases included children and elderly adults, but as a group were
significantly more likely to have used intravenous drugs than hospitalised
control patients. CONCLUSION: Both HCV and probable non-A-E virus(es) were
important causes of acute NANB hepatitis during the early 1970s.

PMID: 11198574 [PubMed - indexed for MEDLINE]

708: Mil Med. 2001 Jan;166(1):11-3.

Comment in:
    Mil Med. 2001 Jul;166(7):ii.

The cost-saving potential of prevaccination antibody tests when implementing a
mass immunization program.

Memish ZA, Oni GA, Bannatyne RM, Qasem L.

Department of Infection Prevention and Control, King Fahad National Guard
Hospital, Riyadh 11426, Saudi Arabia.

A seroprevalence study of hepatitis A virus (HAV), hepatitis B virus (HBV), and
varicella-zoster virus (VZV) was carried out among Saudi Arabian National Guard
soldiers with the objective of determining the cost-saving potential of
prevaccination antibody tests when implementing an immunization program for the
soldiers. A systematic sampling of 450 blood samples from 1,350 soldiers who
donated blood at our hospital was carried out. Antibody tests were performed
using the enzyme-linked immunosorbent assay method. The seropositivity rates for 
antibodies to HAV, HBV, and VZV were 97.5, 17.8, and 88.5%, respectively.
Comparing the cost of prevaccine screening with that of universal vaccination, it
was estimated that savings of 76 and 32% could be effected for HAV and VZV.
Conversely, screening for HBV before immunization could increase the cost of
vaccinating against the disease by 49%. A seroprevalence study could be a useful 
cost-saving approach to a mass immunization program against endemic, natural
immunity-conferring diseases.

PMID: 11197089 [PubMed - indexed for MEDLINE]

709: Med Sci Monit. 2000 Sep-Oct;6(5):989-93.

Changing epidemiology of hepatitis A virus infection--a comparative study in
central eastern Poland (1990-1999).

Polz-Dacewicz MA, Policzkiewicz P, Badach Z.

Department of Virology, Medical University, ul. Lubartowska 85, 20-123 Lublin,
Poland. mpolz@asklepios.am.lublin.pl

A comparative seroepidemiological study (1990 vs. 1998/99) on HAV infection, was 
carried out in population from middle-eastern Poland. Anti-HAV was tested in 1450
subjects from 0 to over 50 years of age and the results were compared with those 
observed in 1990, in 1000 individuals of the same age range and from the same
geographical area. Overall anti-HAV prevalence was 58.4% in 1990 vs. 30.6% in
1998/99. This decline of HAV infection in Polish population indicates that the
number of non-immune adults is increasing, with higher risk of symptomatic
infection in the near future. The surveillance and prevalence data presented here
have implications for developing the strategy for use of hepatitis A vaccine.

Publication Types: 
    Comparative Study

PMID: 11208443 [PubMed - indexed for MEDLINE]

710: Clin Infect Dis. 2001 Jan 15;32(2):297-9. Epub 2000 Dec 28.

Comment in:
    Clin Infect Dis. 2001 Nov 1;33(9):1613.

Occurrence of acute hepatitis A in patients infected with human immunodeficiency 
virus.

Fonquernie L, Meynard JL, Charrois A, Delamare C, Meyohas MC, Frottier J.

Service des Maladies Infectieuses et Tropicales, Hôpital Saint-Antoine, Paris,
France. lfonq@club-internet.fr

We conducted a descriptive study in 9 cases of acute hepatitis A diagnosed in
patients with human immunodeficiency virus (HIV). Despite the small number of
cases studied, the results indicate that moderate HIV infection does not impair
the natural history of acute hepatitis A.

PMID: 11170922 [PubMed - indexed for MEDLINE]

711: J Med Virol. 2001 Feb;63(2):88-95.

Molecular epidemiology of hepatitis A virus in Amsterdam, the Netherlands.

Bruisten SM, van Steenbergen JE, Pijl AS, Niesters HG, van Doornum GJ, Coutinho
RA.

Municipal Health Service, Division of Public Health and Environment, Amsterdam,
The Netherlands. sbruisten@gggd.amsterdam.nl

The transmission of sporadic community-acquired hepatitis A virus (HAV) among
different risk groups in Amsterdam was verified by applying molecular techniques 
on fecal samples. These were collected in 1997/1998 from 33 persons with HAV
infection that was confirmed serologically. From 8 of these persons serial stool 
samples were collected. Nested RT-PCR targeting the VP3-VP1 and VP1-P2a regions
followed by sequence analysis established the duration of fecal HAV RNA excretion
in stool and the epidemiological molecular relationships between patients. The
samples of 31 patients were RT-PCR positive, of which 24 were positive for both
regions. Fecal HAV shedding was found to occur for at least 33 days after onset
of disease, which was the longest time span tested. Sequencing showed that the
hepatitis A virus subgenotype circulating among persons from Moroccan descent
(type IB) was different from the subgenotype circulating among Dutch homosexual
men (type IA). If the latter is endemic in the Netherlands, its presence is of
importance to the national vaccination strategy. Copyright 2001 Wiley-Liss, Inc.

PMID: 11170043 [PubMed - indexed for MEDLINE]

712: Liver. 2001 Feb;21(1):45-9.

Suppression of hepatitis B virus replication mediated by hepatitis A-induced
cytokine production.

van Nunen AB, Pontesilli O, Uytdehaag F, Osterhaus AD, de Man RA.

Department of Hepatogastroenterology, Erasmus University Hospital Rotterdam, The 
Netherlands.

BACKGROUND: Acute hepatitis A virus (HAV) infection can cause severe hepatitis
especially in patients with underlying chronic liver disease. In patients with
pre-existing chronic hepatitis B (HBV) acute HAV infection can suppress HBV
replication. The exact mechanism of HBV suppression during acute HAV infection is
still a subject of debate. One mechanism may be the production of HAV
infection-induced cytokines leading to suppression of HBV replication and viral
clearance. AIM: To evaluate cytokine production and HBV-specific
lympho-proliferative responses (LPR) during acute HAV infection in a patient with
chronic HBV infection-clearing markers of active HBV replication. DESIGN: Early
detection of a case of acute HAV infection in an HBeAg-positive, HBV DNA-positive
chronic HBV patient treated with lamivudine. RESULTS: At the time of HAV
infection a sharp peak in the gamma-interferon (IFN-gamma) level occurred just
before the rise in serum transaminase activity. This was subsequently followed by
a decrease in HBV DNA and HBeAg below the limit of detection of the assay.
However the HBV-specific T-cell response was not modified. After resolution of
the acute HAV infection and withdrawal of antiviral therapy HBV replication
relapsed. CONCLUSION: The sharp rise in IFN-gamma production mediated by the
acute HAV infection may be pivotal in the suppression of HBV replication in
chronic hepatitis B.

PMID: 11169072 [PubMed - indexed for MEDLINE]

713: Zhonghua Yi Xue Za Zhi (Taipei). 2000 Nov;63(11):798-803.

Need for vaccination of susceptible food handlers against hepatitis A in Taiwan.

Yu MI, Lee SD, Lu RH, Chan CY, Wang YJ, Chang FY, Lo KJ.

Division of Gastroenterology, Department of Medicine, Taipei Veterans General
Hospital, National Yang-Ming University School of Medicine, Taipei, Taiwan, ROC.

BACKGROUND: With the improvement in the socioeconomic situation and general
hygiene standards in Taiwan, the prevalence of antibodies to the hepatitis A
virus (anti-HAV) in the general population has declined markedly in recent years.
To avoid food-borne outbreaks of HAV infection caused by susceptible food
handlers in Taiwan, we investigated the seroprevalence of anti-HAV among the
target population and also evaluated the immunogenicity and reactogenicity of the
inactivated hepatitis A vaccine in this study group. METHODS: Two hundred and
forty-four food handlers employed in four restaurants at Taipei Veterans General 
Hospital participated in the anti-HAV serologic screening program in July 1997.
Of them, 48 susceptible food handlers received three doses of 720 enzyme-linked
immunosorbent units of inactivated hepatitis A vaccine at 0, 1 and 6 months.
RESULTS: Of the 244 food handlers who underwent anti-HAV serologic screening, 169
(69.3%) were anti-HAV positive. The seroprevalence of anti-HAV was related to
age: 91.5% of food handlers over 30 years of age were positive for anti-HAV but
only 22.8% of food handlers younger than 30 were anti-HAV positive. Anti-HAV
response was observed in all vaccinees after a booster vaccination at month 6.
The response persisted to 1 year. The side-effects of the vaccinations were
minimal. CONCLUSIONS: Susceptible food handlers should receive hepatitis A
vaccination. Hepatitis A vaccine is safe and immunogenic in this target
population.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11155755 [PubMed - indexed for MEDLINE]

714: J Viral Hepat. 2001 Jan;8(1):83-6.

Transient hepatopulmonary syndrome in a patient with acute hepatitis A.

Regev A, Yeshurun M, Rodriguez M, Sagie A, Neff GW, Molina EG, Schiff ER.

Center for Liver Diseases, Division of Hepatology, University of Miami School of 
Medicine, Miami, FL 33136, USA.

The hepatopulmonary syndrome is defined as the triad of liver disease, hypoxaemia
and intrapulmonary vascular dilatation. This syndrome has been described in
patients with liver cirrhosis, noncirrhotic portal hypertension, and fulminant
hepatic failure, however, there are no previous descriptions of hepatopulmonary
syndrome in patients with acute nonfulminant viral hepatitis. We report a
47-year-old, previously healthy man that presented with acute hepatitis A, and
developed progressive dyspnoea, platypnoea and orthodeoxia with no evidence of
parenchymal or thromboembolic lung disease. PaO2 on room air was 58 mmHg, O2
saturation was 88% and alveolar-arterial O2 gradient was 62%. During his
hospitalization serum albumin level decreased to 3.1 g/dl and prothrombin time
was prolonged to 16.8 s, however, he remained alert with no signs of hepatic
encephalopathy. Contrast echocardiography revealed left heart chamber
opacification 3-4 cardiac cycles after the opacification of the right heart
chamber, consistent with hepatopulmonary syndrome. During the following days
there was a gradual improvement in the patient's condition, with resolution of
his dyspnoea and gradual increase of PaO2. Repeat contrast echocardiography and
PaO2 determinations, 3 weeks later, were normal. On long-term follow-up the
patient remained asymptomatic with normal liver function tests and normal O2
saturation. This report indicates that hepatopulmonary syndrome may be a
transient manifestation of acute hepatitis A in the absence of fulminant liver
failure.

Publication Types: 
    Case Reports

PMID: 11155156 [PubMed - indexed for MEDLINE]

715: Clin Microbiol Rev. 2001 Jan;14(1):38-58.

Erratum in:
    Clin Microbiol Rev 2001 Jul;14(3):642.

Hepatitis A: old and new.

Cuthbert JA.

Department of Internal Medicine, UT Southwestern Medical Center at Dallas,
Dallas, Texas 75390-9151, USA. jennifer.cuthbert@utsouthwestern.edu

The hepatitis A virus (HAV), a picornavirus, is a common cause of hepatitis
worldwide. Spread of infection is generally person to person or by oral intake
after fecal contamination of skin or mucous membranes; less commonly, there is
fecal contamination of food or water. Hepatitis A is endemic in developing
countries, and most residents are exposed in childhood. In contrast, the adult
population in developed countries demonstrates falling rates of exposure with
improvements in hygiene and sanitation. The export of food that cannot be
sterilized, from countries of high endemicity to areas with low rates of
infection, is a potentially important source of infection. After ingestion and
uptake from the gastrointestinal tract, the virus replicates in the liver and is 
excreted into the bile. Cellular immune responses to the virus lead to
destruction of infected hepatocytes with consequent development of symptoms and
signs of disease. Humoral immune responses are the basis for diagnostic serologic
assays. Acute HAV infection is clinically indistinguishable from other causes of 
acute viral hepatitis. In young children the disease is often asymptomatic,
whereas in older children and adults there may be a range of clinical
manifestations from mild, anicteric infection to fulminant hepatic failure.
Clinical variants include prolonged, relapsing, and cholestatic forms. Management
of the acute illness is supportive, and complete recovery without sequelae is the
usual outcome. Research efforts during World War II led to the development of
passive immunoprophylaxis. Pooled immune serum globulin is efficacious in the
prevention and attenuation of disease in exposed individuals. More recently,
active immunoprophylaxis by vaccination has been accomplished. Future eradication
of this disease can now be contemplated.

Publication Types: 
    Review

PMID: 11148002 [PubMed - indexed for MEDLINE]

716: Pediatr Infect Dis J. 2000 Dec;19(12):1187-8.

Hepatitis A vaccine.

Bell BP.

Hepatitis Branch, Centers for Disease Control and Prevention, Atlanta, GA, USA.

Inactivated hepatitis A vaccines are highly immunogenic and efficacious. Because 
of their high disease rates and importance as a reservoir of transmission to
others, children should be the primary focus of vaccination. A long-term strategy
of sustained routine vaccination of children living in areas with consistently
elevated hepatitis A rates has been adopted. Ultimately, elimination of HAV
transmission will require vaccination of all children in the US. This effort
would be facilitated by the availability of vaccine formulations or schedules for
use in infants or children in the second year of life, and combination vaccines
that include hepatitis A.

Publication Types: 
    Review

PMID: 11144382 [PubMed - indexed for MEDLINE]

717: J Med Virol. 2001 Jan;63(1):1-7.

Inactivated hepatitis A vaccine-induced antibodies: follow-up and estimates of
long-term persistence.

Van Herck K, Van Damme P.

Centre for the Evaluation of Vaccination, University of Antwerp, Belgium.
kvherck@uia.ua.ac.be

To estimate the long-term persistence of anti-HAV antibodies, 120 (schedule 0-6) 
and 194 (schedule 0-12) adults were vaccinated and followed-up annually for 6
years. Shortly after the last dose, anti-HAV levels fell sharply (annual decline 
rate delta > 65%). Thereafter, delta diminished to 10-15%. GMTs 5.5 years after
the last dose were 522 mIU/ml (0-6 group) and 749 mIU/ml (0-12 group); all
subjects except one maintained detectable antibodies. The average delta over the 
whole follow-up period was 15-20%, resulting in an estimated persistence of
anti-HAV levels > or =20 mIU/ml for 20-25 years. These estimates were similar for
both applied calculation methods (GMT or individual based) and both vaccination
schedules. Because the individual antibody levels tended to stabilise between the
last two measurements, the hypothesis of a slow, log-linear decrease and its
matching calculation methods might be subject to reconsideration. With the
current methodology, however, detectable antibodies are estimated to persist for 
20-25 years.

Publication Types: 
    Clinical Trial
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 11130881 [PubMed - indexed for MEDLINE]

718: J Immunol Methods. 2000 Dec 1;246(1-2):13-24.

Assessment of synthetic peptides for hepatitis A diagnosis using biosensor
technology.

Gómara MJ, Ercilla G, Alsina MA, Haro I.

Departament de Química de Pèptids i Proteïnes, IIQAB-CSIC, Jordi Girona 18-26,
08034, Barcelona, Spain.

In the present work we demonstrate the application of a commercial biosensor
instrument (BIACORE 1000, Biacore AB, Uppsala) for the detection of antibodies
against the hepatitis A virus (HAV) in human serum samples using linear and
branched synthetic peptides related to the VP3 capsid protein of HAV. We also
studied the conformation of the synthetic peptides by circular dichroism (CD) in 
order to analyse the changes in secondary structure of the constructs that could 
influence their recognition by antibodies. Linear and dimeric VP3(110-121)
multiple antigen peptides (MAP) were the most sensitive and appropriate for
serological studies of serum from HAV infected patients using BIACORE.
Immobilization of tetrameric MAPs via amine groups apparently failed to preserve 
the active conformation of the peptide epitope since it led to lower antibody
binding compared to linear and dimeric peptides. The CD analysis showed that the 
tetrameric MAP constructs tend to adopt a beta-sheet structure due to
intermolecular aggregation, which limits epitope accessibility. Our results
demonstrate the value of biospecific interaction analysis technology using
synthetic peptides for the diagnosis of acute hepatitis A.

Publication Types: 
    Comparative Study
    Evaluation Studies

PMID: 11121543 [PubMed - indexed for MEDLINE]

719: Vaccine. 2000 Nov 22;19(7-8):844-9.

Prevalence of hepatitis A virus infection in sewage plant workers of Central
Italy: is indication for vaccination justified?

Bonanni P, Comodo N, Pasqui R, Vassalle U, Farina G, Lo Nostro A, Boddi V,
Tiscione E.

Department of Public Health and Epidemiology, University of Florence, Florence,
Italy. bonanni@dsp.igiene.unifi.it

Prevalence of antibodies to hepatitis A virus (HAV) was studied in a group of 65 
sewage plant workers living in Tuscany, Central Italy. In order to evaluate the
effect of several confounders (age, place of birth, income, educational degree,
sea-food consumption, etc.), subjects under study were matched with 160 other
workers residing in the same area. Anti-HAV was detected in about 51% of sewage
workers and 44% of other employees. The difference was not statistically
significant. Both univariate and multivariate analysis showed that the main
variables related to previous HAV infection were increasing age (P<0.001), birth 
in Southern Italy (P<0.01) and lower educational degree (P<0.001). Although other
studies in Northern and Central Europe showed a slightly higher risk of infection
in sewage workers versus general population, lack of evidence of occupational
risk in Italy might be explained by the relative importance of a higher degree of
viral circulation in the past. The changing epidemiology of HAV infection in
Italy with increasing numbers of susceptibles in adults and the potential
occupational risk suggest that the present indication to immunize sewage plant
workers against hepatitis A should be maintained.

PMID: 11115708 [PubMed - indexed for MEDLINE]

720: Am J Public Health. 2000 Dec;90(12):1942-6.

Factors influencing a communitywide campaign to administer hepatitis A vaccine to
men who have sex with men.

Friedman MS, Blake PA, Koehler JE, Hutwagner LC, Toomey KE.

Georgia Division of Public Health, Centers for Disease Control and Prevention,
Atlanta 30333, USA. mff7@cdc.gov

OBJECTIVES: A hepatitis A outbreak among men who have sex with men (MSM) led to a
publicly funded vaccination campaign. We evaluated the MSM community's response. 
METHODS: A cohort of MSM from 5 community sites was surveyed. RESULTS:
Thirty-four (19%) of 178 potential vaccine candidates received the vaccine during
the campaign. We found a linear relation between the number of exposures to
campaign information and the likelihood of vaccination (P < .001). Vaccination
was independently associated with awareness of the outbreak and the vaccine,
having had sexual relations with men for 12 years or longer, having recently
consulted a physician, and routinely reading a local gay newspaper. CONCLUSIONS: 
The difficult task of vaccinating MSM can be aided by repetitive promotional
messages, especially via the gay media.

Publication Types: 
    Evaluation Studies

PMID: 11111274 [PubMed - indexed for MEDLINE]

721: J Gastroenterol Hepatol. 2000 Oct;15 Suppl:G94-9.

Asian perspectives on viral hepatitis A.

Lee SD.

Department of Medicine, Taipei Veterans General Hospital, Taiwan.
sdlee@vghtpe.gov.tw

Recent decades have witnessed a marked decline in the prevalence of hepatitis A
virus (HAV) infection in Asian populations, especially in children. This is
attributable to general improvements in socio-economic status and hygiene, which 
have, in turn, made a large population of young adults susceptible to the
disease. The HAV infection rarely results in death and mortality is
age-dependent. According to previous reports, it may be more severe in persons
with underlying chronic liver disease (CLD). Because most parts of Asia are areas
of endemic hepatitis B and C virus infection, where chronic hepatitis B and C are
the most important causes of CLD, it is therefore imperative for patients with
CLD to be protected against HAV infection. Several studies have been conducted
into the success of immunization against HAV in different risk groups. Given the 
increasing potential for HAV epidemics and the success and safety of the HAV
vaccines, mass immunization against the infection seems possible and rational in 
Asia.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 11101002 [PubMed - indexed for MEDLINE]

722: Acta Paediatr Taiwan. 2000 Sep-Oct;41(5):246-50.

Recent trends in viral hepatitis among Japanese children.

Koike M, Kobayashi M, Okuda S, Okuda M, Tanaka T, Naito Y.

Department of Pediatrics, Wakayama Medical College, Japan.

The prevalence of viral hepatitis in Japan were very high as peak HBsAg positive 
rate of 2-3% and HBsAb positive rate of 25% of peoples born in the 1930th and
1940th. But recently in Japan hepatitis A has completely eradicated and hepatitis
B and C were seldom seen in our pediatric clinics. Many strategies were done
beginning from sterilized water service to introduction of HCV-Ab screening
system for blood transfusion in 1989. Many efforts had combined to get final
success. The historical views of epidemics of viral hepatitis and maneuvers to
improve were introduced here.

PMID: 11100521 [PubMed - indexed for MEDLINE]

723: Rev Esp Enferm Dig. 2000 Aug;92(8):508-17.

Prevalence of hepatitis A virus antibodies in patients with chronic liver
diseases.

[Article in English, Spanish]

López Serrano A, Antón Conejero MD, Alcaraz Soriano MJ, García del Castillo G,
Gómez Pajares F, Moreno-Osset E.

Digestive System Medicine Service, Hospital Universitario Dr. Peset, Valencia,
Spain. anlopezs@comv.es

OBJECTIVE: The age of persons with hepatitis A virus (HAV) infection in the
general population has risen; these persons are at increased risk of clinically
severe disease, especially patients with chronic liver disease. The aim of the
present study was to analyze the prevalence of total antibodies against HAV in
patients with chronic liver disease. METHODS: In a prospective study carried out 
between September 1998 and June 1999, 180 patients seen in the chronic liver
disease outpatient department were studied. The prevalence of total anti-HAV
antibodies was determined by age group, etiology and degree of histological
damage, and according to the antecedents of risk for parenteral infection. A
nonconditional logistic regression model was fitted with anti-HAV positivity as
the dependent variable. RESULTS: Mean age was 44.1 years, with an anti-HAV
prevalence of 77.2% (varying from 42.9% in the 21-25-year-old group to more than 
83% in patients > 56-years old). Differences across groups regarding other
categories (histological damage, etiology and history of parenteral or drug use) 
were not statistically significant, but the probability of anti-HAV positivity
increased with age and a history of drug addiction. CONCLUSIONS: The prevalence
of total anti-HAV antibodies is high among patients with chronic liver disease.
We therefore recommend this test before vaccination against HAV, until current
recommendations on universal childhood vaccination are implemented, in order to
prevent hepatitis A epidemics in the general population.

PMID: 11084818 [PubMed - indexed for MEDLINE]

724: West J Med. 2000 Nov;173(5):325-9.

Comment in:
    West J Med. 2000 Nov;173(5):329-30.

Screening travelers for hepatitis A antibodies: an observational cost-comparison 
study of vaccine use.

Lee KK, Beyer-Blodget J.

Department of Medicine, Kaiser Permanente Medical Center, 2025 Morse Ave,
Sacramento, CA 95825-2115, USA. kenneth.k.lee@ncal.kaiperm.org

OBJECTIVES: To measure the seroprevalence of antibodies to hepatitis A virus
(anti-HAV) in a health plan population of travelers and to determine whether
prevaccination screening for anti-HAV can reduce unnecessary vaccination and thus
promote the most effective, economic use of hepatitis A vaccine. DESIGN:
Observational, cost-comparison study. SETTING: Central injection clinic of a
health maintenance organization medical center. SUBJECTS: Five hundred
twenty-seven adults who denied having previous hepatitis A or vaccination. MAIN
OUTCOME MEASURES Subgroups with the greatest prevalence of anti-HAV seen between 
June 1995 and April 1996 for immunizations before traveling to nonindustrialized 
countries. Relative costs of their screening and immunization. RESULTS: The
presence of anti-HAV precluded the need for vaccination in 148 subjects (28.1%). 
The highest prevalence of anti-HAV (82.7%) was found in subjects born in
nonindustrialized countries (62/75), in subjects who had previously traveled to
areas of endemic hepatitis A (32.1% [135/420]), and in subjects born before 1945 
(29.2% [92/315]). Costs of screening and vaccinating travelers were cheapest if
prevaccination antibody sera testing was limited to subjects born in
nonindustrialized countries and those born before 1945. CONCLUSIONS:
Prevaccination screening of travelers for hepatitis A can be done selectively on 
the basis of age and country of origin. This strategy could lead to a more
economic use of the vaccine and clinic resources.

PMID: 11069868 [PubMed - indexed for MEDLINE]

725: J Infect Dis. 2000 Dec;182(6):1583-7. Epub 2000 Oct 13.

Erratum in:
    J Infect Dis 2001 Feb 1;183(3):521.

Comment in:
    J Infect Dis. 2001 Aug 1;184(3):390-1.

The possible role of hepatitis A virus in the pathogenesis of atherosclerosis.

Zhu J, Quyyumi AA, Norman JE, Costello R, Csako G, Epstein SE.

Cardiovascular Research Institute, MedStar Research Institute, Washington
Hospital Center, Washington, DC 20010, USA.

The possible association between hepatitis A virus (HAV) infection and coronary
artery disease (CAD) was studied. Blood from 391 patients undergoing coronary
angiography was tested for serum IgG antibodies to HAV and C-reactive protein
(CRP). Of the 391 patients, 205 (52%) had anti-HAV IgG antibodies. CAD prevalence
was 74% in HAV-seropositive and 52% in HAV-seronegative patients (P<.0001);
significance persisted after adjustment for either traditional CAD risk factors
or for risk factors plus other infectious agents (cytomegalovirus, Chlamydia
pneumoniae, Helicobacter pylori, and herpes simplex virus). In addition, CRP
levels were significantly higher in HAV-seropositive than in HAV-seronegative
patients (P=. 013) in both univariate and multivariate analyses. Logistic
regression analysis demonstrated that HAV seropositivity is an independent
predictor of risk for CAD and elevated CRP levels. HAV infection is therefore
associated with CAD, which raises the possibility that this virus may play a
causal role in atherogenesis.

Publication Types: 
    Comparative Study

PMID: 11069227 [PubMed - indexed for MEDLINE]

726: N Z Med J. 2000 Sep 22;113(1118):394-6.

Comment in:
    N Z Med J. 2001 Feb 9;114(1125):50.

The prevalence of viral hepatitis (HAV, HBV and HCV) in the Christchurch
community.

Chapman BA, Burt MJ, Frampton CM, Collett JA, Yeo KH, Wilkinson ID, Cook HB,
Barclay MJ, Ross AG, George PM.

Christchurch Hospital.

AIM: To determine the prevalence of hepatitis A (HAV), hepatitis B (HBV) and
hepatitis C (HCV) in adults randomly selected from the Christchurch community.
METHODS: A list of names was randomly generated from the Christchurch electoral
roll and subjects were sequentially contacted and invited to participate. A blood
sample was taken and tested for hepatitis A (IgG anti-HAV antibody), hepatitis B 
(HBsAg and anti-HBc) and HCV (anti-HCV antibody) using Abbott Elisa kits.
Subjects positive for HBsAg were also tested for HBeAg/HBV DNA. Those positive
for anti-HBc were tested for anti-HBs. HCV antibody positive samples were tested 
for HCV RNA using PCR. RESULTS: 1064 subjects (30.3% of those invited)
participated in the study. The prevalence of HAV antibodies was 27.9%, and
increased with age. The overall prevalence of HBV markers was 42/1064 (4.2%), and
of these 0.3% were HBsAg positive and 3.9% were considered immune. No gender or
ethnic differences in these proportions were observed. The seroprevalence of HVC 
antibody was 3/1064 (0.3%), two of whom were also PCR positive for HCV RNA.
CONCLUSION: In the Christchurch community there was a high prevalence of
antibodies to HAV, which increased with age. The prevalence of HBsAg and antibody
to HCV were both low at 0.3%.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11062814 [PubMed - indexed for MEDLINE]

727: J Gastroenterol Hepatol. 2000 Sep;15(9):1043-7.

Detection of hepatitis A viral RNA in sera of patients with acute hepatitis A.

Kwon OS, Byun KS, Yeon JE, Park SH, Kim JS, Kim JH, Bak YT, Kim JH, Lee CH.

Department of Internal Medicine, Korea University College of Medicine, Seoul.

BACKGROUND AND AIMS: The Detection of hepatitis A virus (HAV) is important for
diagnosis and epidemiological studies of hepatitis A. The polymerase chain
reaction (PCR) technique is a sensitive test to detect HAV-RNA in specimens. The 
aims of the present study were to clarify the detection rate of serum HAV-RNA by 
PCR and the natural history of HAV viraemia, and to determine the correlation
between viraemia and the clinical characteristics in patients with acute
hepatitis A. METHODS: Hepatitis A virus RNA was tested in 74 serum samples which 
were serially collected from 27 patients with acute hepatitis A. A nested reverse
transcription (RT)-PCR for HAV-RNA was performed with primer sets located at the 
VP1 region of the HAV genome and the PCR products were electrophoresed on a 1.5% 
agarose gel. RESULTS: Hepatitis A virus RNA was found in 18 of 27 (67%) patients 
with hepatitis A. There were no significant differences between groups positive
and negative for HAV-RNA in clinical and laboratory data, except the time
interval between clinical onset and initial serum sampling for RT-PCR (10 +/- 6
vs 19 +/- 14 days) and the alanine aminotransferase (ALT) level at initial serum 
sampling for RT-PCR (1436 +/- 1416 vs 518 +/- 432 IU/L). The mean duration of HAV
viraemia was 30 +/- 19 days (range, 5-59 days). The duration of HAV viraemia and 
duration of abnormal ALT levels from clinical onset were positively correlated (r
= 0.685, P = 0.007). CONCLUSION: In conclusion, HAV-RNA RT-PCR is a useful tool
to detect HAV viraemia and to study the molecular epidemiology of HAV infection.

PMID: 11059935 [PubMed - indexed for MEDLINE]

728: Indian J Gastroenterol. 2000 Oct-Dec;19(4):165-7.

Use of filter paper disks for hepatitis A surveillance.

Chitambar SD, Chadha MS.

Hepatitis Department, National Institute of Virology, Pune.

BACKGROUND: Venous blood collection is a cumbersome and uncomfortable procedure
during hepatitis A surveillance. Collection of capillary blood by finger prick is
an alternative method. AIM: To evaluate the reactivity of capillary
blood/anti-hepatitis A virus (HAV) IgG stored on filter paper disks for detection
of anti-HAV antibody. METHODS: Venous blood specimens were collected from healthy
individuals. Simultaneous capillary blood specimens obtained by finger prick were
stored on filter paper disks. A reference standard of anti-HAV IgG in known
concentrations was spotted on filter paper disks. The reactivities of anti-HAV
IgG and capillary blood specimens eluted from filter paper disks were tested by
blocking ELISA for detection of anti-HAV antibody. The results were evaluated by 
comparing optical density (OD) and neutralization values with those obtained for 
WHO anti-HAV IgG stored in liquid phase and homologous venous blood specimens,
respectively. RESULTS: Among both venous and capillary-blood specimens stored for
10 days, percent neutralization shown by the same 46 specimens was > 50 and that 
of the same 3 specimens was < 50, indicating anti-HAV positivity and negativity, 
respectively. There was significant correlation between the OD values displayed
by anti-HAV IgG from liquid phase and that eluted from filter paper disk (p <
0.01). Sixteen serum specimens stored for a period of 2 months showed results
similar to those of the corresponding filter paper disk elutes. CONCLUSION: Use
of filter paper disks could be a suitable choice for pre- and post-immunization
collection of blood specimens during hepatitis A surveillance.

Publication Types: 
    Clinical Trial
    Comparative Study
    Controlled Clinical Trial

PMID: 11059181 [PubMed - indexed for MEDLINE]

729: Eur J Epidemiol. 2000 Jun;16(6):507-10.

The changing epidemiological pattern of hepatitis A in an urban population of
India: emergence of a trend similar to the European countries.

Das K, Jain A, Gupta S, Kapoor S, Gupta RK, Chakravorty A, Kar P.

Department of Medicine, Maulana Azad Medical College and Associated Lok Nayak
Hospital, New Delhi, India.

The present study was undertaken to determine the seroprevalence of the antibody 
against hepatitis A virus (IgG anti-HAV) in an urban population sample from Delhi
(India) and to assess any change in the epidemiological pattern of HAV infection 
in this part of the world. A total of 500 healthy subjects were enrolled and
divided into groups on the basis of age, sex and per capita income and evaluated 
for the presence of IgG anti HAV antibodies using a commercially available kit.
The mean age of all the subjects was 32.6 +/- 13.2 yr. and the male:female ratio 
was 1.5:1. The overall prevalence of IgG anti-HAV in all subjects was 71.2%
(356/500). The prevalence in subjects >35 years (92.1% [186/202]) was
significantly higher than that in subjects <35 years (92.1% [186/202]) was
significantly higher than in subjects <35 years (57% [170/298]). No statistically
significant difference was observed between male and female subjects (71.4%
[217/304] vs. 70.9% [139/196]) or between subjects belonging to middle and low
socioeconomic groups (68.9% [135/196] vs. 72.7% [221/304]). These findings when
compared with the results that were obtained in 1982, showed a decreasing
prevalence of IgG anti-HAV, most significantly in younger age groups (16-35
years). Thus, we may conclude that the seroepidemiology of hepatitis A virus
infection in urban population of India seems to be changing with seroprevalence
in the younger population approaching a figure similar to that of the more
developed European countries.

Publication Types: 
    Comparative Study

PMID: 11049092 [PubMed - indexed for MEDLINE]

730: Ren Fail. 2000;22(5):635-40.

Acute renal failure complicating nonfulminant hepatitis a in HLA-B27 positive
patient.

Brncić N, Matić-Glazar D, Visković I, Grzetić M, Racki S.

Department of Infectious Diseases Clinical Hospital Center of Rijeka, Croatia.
perol@mamed.medri.hr

Here we report the case of a previously healthy 32-year-old HLA B27 positive male
who developed completely reversible acute oliguric renal failure in the course of
nonfulminant hepatitis A infection. This is a rare complication of uncertain
etiology. B27 positive individuals are prone to a number of immune system
derangements including overreacting in interactions with some microbiologic
agents. We made our consideration on the basis of some experimental models and
the presumed pathogenesis of reactive arthritis in these individuals. As a result
here we postulate a hepatitis A virus-triggered, immune mediated mechanism of
renal injury restricted to genetically susceptible (i.e. B27 positive)
individuals. In regard to this hypothesis we warrant additional HLA-profiles and 
future similar cases for further confirms and conclusions.

Publication Types: 
    Case Reports

PMID: 11041295 [PubMed - indexed for MEDLINE]

731: Vaccine. 2000 Oct 15;19(4-5):470-4.

Hepatitis A and B in children and adolescents--what can we learn from Puglia
(Italy) and Catalonia (Spain)?

Lopalco PL, Salleras L, Barbuti S, Germinario C, Bruguera M, Buti M, Domínguez A.

Department of Internal Medicine and Public Medicine, Section of Hygiene,
University of Bari, Policlinico, Piazza G. Cesare 11, 70124 Bari, Italy.

Viral hepatitis remains a major contributor to the global disease burden. Mass
immunisation strategies against hepatitis B have been adopted by more than 90
developing and industrialised countries. Countries with low hepatitis A
endemicity are experiencing cyclical outbreaks and an epidemiological shift, with
larger numbers of individuals at risk of infection at an older age, resulting in 
increased morbidity. The high cost of outbreaks in these countries has made
immunisation strategies cost-effective. The development of a vaccine against
hepatitis A and a combined vaccine against hepatitis A and hepatitis B offers
potentially exciting opportunities for a preventative approach in areas of both
low and high endemicity. Existing mass immunisation programmes against hepatitis 
B will facilitate the adoption of joint strategies illustrated by the examples of
Puglia (Italy) and Catalonia (Spain).

PMID: 11027810 [PubMed - indexed for MEDLINE]

732: Southeast Asian J Trop Med Public Health. 2000 Mar;31(1):25-8.

Current seroprevalence of hepatitis A virus infection among kindergarten children
and teachers in Taiwan.

Lin DB, Tsai TP, Yang CC, Wang HM, Yuan SC, Cheng MH, You SL, Chen CJ.

School of Medical Technology, Chung Shan Medical and Dental College, Taichung,
Taiwan.

Taiwan was a hyperendemic area for hepatitis A virus (HAV) infection before the
late 1980s. The seroprevalence of HAV infection was higher than 90% with most HAV
infection occurring during childhood. This study was to estimate the
seroprevalence of HAV infection among preschool children in central Taiwan. A
community-based survey was carried out in 54 kindergartens in 10 urban areas, 10 
rural areas and 2 aboriginal areas randomly selected through stratified sampling.
Serum samples of 2,549 healthy preschool children and 104 teachers in study
kindergartens were screened for the HAV antibodies (anti-HAV) by means of a
commercially available microparticle enzyme immunoassay (AxSYM HAVAB). Among
aboriginal kindergarten children, more than 96% of them were anti-HAV
seropositive due to a mass HAV vaccination program. In urban and rural areas,
kindergarten children had a very low prevalence of anti-HAV (0.4%) in contrast to
a high seroprevalence in their teachers (78%). There was no gender difference in 
seroprevalence of anti-HAV, while the anti-HAV seroprevalence was significantly
higher in urban areas than in rural areas. Crowdedness of living in urban areas
might facilitate the person-to-person transmission of infectious agents.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11023060 [PubMed - indexed for MEDLINE]

733: Southeast Asian J Trop Med Public Health. 2000 Mar;31(1):21-4.

Seroprevalence of hepatitis A virus and varicella zoster antibodies in a Javanese
community (Yogyakarta, Indonesia).

Juffrie M, Graham RR, Tan RI, Widjaja S, Mulyadi S, Weil J, Bock HL.

Department of Pediatrics, Faculty of Medicine, Dr Sardjito Hospital, Gadjah Mada 
University, Yogyakarta, Indonesia.

Hepatitis A virus (HAV) cause an acute inflammation of the liver.
Varicella-zoster virus (VZV) cause chickenpox (varicella) and herpes zoster.
Effective vaccines against hepatitis A and varicella are available for children, 
adolescents and adults. In order to implement an appropriate vaccination policy, 
a baseline to assess the potential benefits and sections of the population who
would benefit most are required. We investigated seroprevalence of hepatitis A
virus and varicella zoster antibodies in a Javanese community. A total of 1,103
subjects were studied. The 600 subjects aged 4 to 9 years were sampled between 23
October and 2 November, 1995. The other subjects were sampled between 12 October 
and 1 November, 1996. The overall prevalence of anti-HAV in cohort was 28.7%.
Anti-HAV seroprevalence rates were below 30% until the age of 15 and below 40%
until the age of 25. The anti-varicella seroprevalence showed only in two thirds 
of seropositive population at the age of 15. The results of the study have
implications for vaccination strategies for both hepatitis A and varicella
zoster.

PMID: 11023059 [PubMed - indexed for MEDLINE]

734: Pediatrics. 2000 Oct;106(4):E54.

Sources of infection among persons with acute hepatitis A and no identified risk 
factors during a sustained community-wide outbreak.

Staes CJ, Schlenker TL, Risk I, Cannon KG, Harris H, Pavia AT, Shapiro CN, Bell
BP.

Salt Lake City-County Health Department, Salt Lake City, Utah, USA.
catherine.staes@hsc.utah.edu

CONTEXT: Hepatitis A is a common vaccine-preventable disease in the United
States. Most cases occur during community-wide outbreaks, which can be difficult 
to control. Many case-patients have no identified source. OBJECTIVE: To identify 
foodborne and household sources of hepatitis A during a community-wide outbreak. 
DESIGN: Serologic and descriptive survey. SETTING: Salt Lake County, Utah.
PARTICIPANTS: A total of 355 household contacts of 170 persons reported with
hepatitis A during May 1996 to December 1996, who had no identified source of
infection; and 730 food handlers working in establishments where case-patients
had eaten. MAIN OUTCOME MEASURE: Prevalence of immunoglobulin M antibodies to
hepatitis A virus (IgM anti-HAV) among household and food service contacts.
RESULTS: Overall, 70 household contacts (20%) were IgM anti-HAV-positive,
including 52% of children 3 to 5 years old and 30% of children <3 years old. In
multivariate analysis, the presence of a child <3 years old (odds ratio [OR]:
8.8; 95% confidence limit [CL]: 2.1,36) and a delay of >/=14 days between illness
onset and reporting (OR: 7. 9; 95% CL: 1.7,38) were associated with household
transmission. Of 18 clusters of infections linked by transmission between
households, 13 (72%) involved unrecognized infection among children <6 years old.
No food handlers were IgM anti-HAV-positive. CONCLUSION: During a community-wide 
outbreak, HAV infection among children was common, was frequently unrecognized,
and may have been an important source of transmission within and between
households. Transmission from commercial food establishments was uncommon.
Ongoing vaccination of children may prevent future outbreaks.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 11015549 [PubMed - indexed for MEDLINE]

735: J Med Virol. 2000 Oct;62(2):144-50.

Genetic relatedness of hepatitis A virus isolates during a community-wide
outbreak.

Robertson BH, Averhoff F, Cromeans TL, Han X, Khoprasert B, Nainan OV, Rosenberg 
J, Paikoff L, DeBess E, Shapiro CN, Margolis HS.

Hepatitis Branch, Division of Viral and Rickettsial Diseases, National Center for
Infectious Diseases, Atlanta, Georgia, USA. bjr1@cdc.gov

In 1993-94, a community-wide outbreak of hepatitis A occurred in Stanislaus
County, California. Stool specimens collected from a sample of 33 case patients
were used to evaluate the duration of hepatitis A virus (HAV) excretion and the
genetic relatedness of HAV isolates. Twenty-four percent of the patients had a
stool sample positive for HAV antigen by enzyme immunoassay, whereas 91% had at
least one stool positive for HAV RNA by RT-PCR amplification. Children were found
to excrete low levels of HAV RNA for up to 10 weeks after the onset of symptoms. 
Analysis of the HAV VP1 amino terminus and VP1/P2A regions showed that a limited 
number of HAV isolates circulated during the epidemic and the majority of the
cases were infected with the same strain. Copyright 2000 Wiley-Liss, Inc.

PMID: 11002242 [PubMed - indexed for MEDLINE]

736: Infect Dis Clin North Am. 2000 Sep;14(3):605-15.

Hepatitis A.

Kemmer NM, Miskovsky EP.

Department of Internal Medicine, University of Texas Medical Branch, Galveston,
USA.

Hepatitis A remains an important cause of community-acquired hepatitis in the
United States and in the world. In recent years, improvements in personal hygiene
and environmental sanitation have led to declines in overall hepatitis A
infection rates in developed countries, although sporadic outbreaks still occur
with similar rates of hospitalization and loss of work. Therapy remains
supportive and prevention holds the key to elimination of widespread infection.
Acute infection can be prevented or attenuated with IG or with inactivated,
highly immunogenic vaccines. Elderly persons and those with advanced liver
disease are at higher risk of the consequences of acute HAV, and they represent
target populations for immediate vaccination. Challenges for the future include
strategies for broad-based population vaccination, including cost-effective
approaches.

Publication Types: 
    Review

PMID: 10987112 [PubMed - indexed for MEDLINE]

737: Ann Trop Med Parasitol. 2000 Jul;94(5):497-502.

Investigations of the epidemiology of infections with hepatitis A virus in
Jamaica.

Brown MG, Lindo JF, King SD.

Department of Microbiology, University of the West Indies, Mona, Kingston,
Jamaica. mgbrown@cwjamaica.com

Between January 1995 and August 1998, a study was conducted to elucidate the
epidemiology of hepatitis A virus (HAV) in Jamaica. Participants were recruited
from six sites across the island. The potential risk factors for transmission
which were studied included age of the individual, gender, residence (urban v.
rural area), sanitary facilities (flush toilet v. pit) and source of domestic
water (indoor plumbing v. other). There were 128 male subjects and 211 female,
aged 3-90 years. The mean ages of the males and females were 24.9 and 25.6 years,
respectively. The seroprevalence of HAV in the study population, estimated by
ELISA, was 59.9%. Logistic regression indicated that age (P < 0.001) and source
of domestic water (P = 0.006) were the major contributors to exposure to HAV. The
rate of exposure to the virus was seen to increase with age. By the age of 10
years, 30% of children had been exposed, and almost 100% of the oldest subjects
were seropositive. Rates of exposure to HAV were higher among households which
had external sources of water, including standpipes, rivers and tanks, than those
with indoor plumbing. Although the seroprevalence of HAV in Jamaica is similar to
that seen in developing countries, the age-related pattern of exposure mirrors
the pattern seen in developed countries.

PMID: 10983562 [PubMed - indexed for MEDLINE]

738: Epidemiol Infect. 2000 Jun;124(3):459-66.

The prevalence of antibodies to hepatitis A virus and its determinants in The
Netherlands: a population-based survey.

Termorshuizen F, Dorigo-Zetsma JW, de Melker HE, van den Hof S, Conyn-Van
Spaendonck MA.

Department of Infectious Diseases Epidemiology, National Institute of Public
Health and the Environment, Bilthoven, The Netherlands.

The prevalence of antibodies to hepatitis A virus was assessed in a Dutch
nationwide sample (n = 7367). A questionnaire was used to study the association
with various sociodemographic characteristics. Overall, 33.8% (95% CI 31.6-36%)
of the population had hepatitis A antibodies. The seroprevalence was less than
10% in people under 35; it increased from 25% at 35 years to 85% at 79 years. For
those 15-49 years of age, Turks (90.9%) and Moroccans (95.8%) had greater
seroprevalence than autochthonous Dutch (20.2%) and other Western people (25%).
Low or middle socio-economic status, as indicated by the highest educational
level achieved, was associated with greater seroprevalence, independently of age 
and reported immunization (OR 2.11 and 1.45; 95% CI 1.67-2.67 and 1.11-1.89,
respectively). These data suggest autochthonous Dutch and other Westerners born
after World War II were exposed to hepatitis A during childhood less frequently
than older birth cohorts. Thus, more susceptibility is likely in the coming
decades. Since this means a greater risk of outbreaks in future years, and since 
morbidity and mortality are more frequent in older persons, studying the cost
effectiveness of selective and general vaccination might be worthwhile.

PMID: 10982070 [PubMed - indexed for MEDLINE]

739: Commun Dis Intell. 2000 Jul;24(7):203-6.

Hepatitis A in south-eastern Sydney 1997-1999: continuing concerns for gay men
and an outbreak among illicit drug users.

Delpech VC, Thackway SV, Young L, Pontivivo G, Smedley E, Morgan K, Ferson MJ.

South East Sydney Public Health Unit, Randwick, New South Wales, Australia.
VDELP@doh.health.nsw.gov.au

The incidence of hepatitis A virus (HAV) in south-eastern Sydney is one of the
highest in Australia with large outbreaks previously associated with male-to-male
sexual contact. We report HAV notification trends over the period 1 June 1997 to 
31 May 1999 for this location. In the first twelve-month period, 233 cases were
notified (crude rate 30.5/100,000 per year) with a peak incidence of 110/100,000 
in males aged 20-39 years. Over 60% of male cases reported male-to-male sexual
contact. The notification rate (crude rate 15.5/100,000) and proportion of males 
(61%) was considerably lower in the following twelve month period with 118 cases 
notified. Less than a third of males reported male-to-male sexual contact. An
outbreak (n = 45) of HAV among illicit drug users and their contacts was detected
in December 1998. The transmission of HAV remains endemic in south-eastern
Sydney. Vaccination among high-risk groups remains an important preventive
strategy.

PMID: 10981351 [PubMed - indexed for MEDLINE]

740: Isr Med Assoc J. 2000 Aug;2(8):598-600.

Hepatitis A associated with other focal infections.

Klar A, Gross-Kieselstein E, Shazberg G, Israeli T, Revel-Vilk S, Hurvitz H.

Pediatric Gastroenterology Unit, Bikur Cholim General Hospital, Hebrew
University-Hadassah Medical School, Jerusalem, Israel. aklar@inter.net.il

BACKGROUND: Concomitant bacterial and viral infection is a well-known phenomenon,
however only very rarely has a bacterial infection been reported during hepatitis
A virus infection. OBJECTIVE: To evaluate retrospectively the clinical records of
children hospitalized with HAV infection for a concomitant infection proved or
presumed to be bacterial. METHOD: A retrospective study was conducted on all the 
children hospitalized with hepatitis A infection from 1988-96 in our center. The 
records were evaluated for a concomitant infection. RESULTS: Of 40 children
hospitalized with HAV infection, 13 were found to have a concomitant infection:
these included 6 with pneumonia, 4 with pyelonephritis and 1 case each of
purulent otitis media, osteomyelitis and staphylococcal bacteremia. CONCLUSION:
In areas where hepatitis A is endemic, a simultaneous infection with hepatitis A 
and other common bacterial infection during childhood may co-exist. A permissive 
role for HAV infection is suggested.

PMID: 10979353 [PubMed - indexed for MEDLINE]

741: Rev Inst Med Trop Sao Paulo. 2000 Jul-Aug;42(4):197-200.

Detection of hepatitis A antibodies by ELISA using saliva as clinical samples.

Oba IT, Spina AM, Saraceni CP, Lemos MF, Senhoras R, Moreira RC, Granato CF.

Department of Virology, Instituto Adolfo Lutz, SP, Brazil. iasbeltoba@hotmail.com

The possibility of detecting acute infection and immunity using body fluids that 
are easier to collect than blood, mainly in children, would facilitate the
investigation and follow-up of outbreaks of hepatitis A (HAV). Our study was
carried out to evaluate the detection of anti-HAV IgM, IgA and total antibodies
in saliva using serum samples as reference. Forty three paired serum and saliva
samples were analyzed. From this total, 24 samples were obtained from children
and 1 from one adult during the course of acute hepatitis A; an additional 18
samples were obtained from health professionals from Adolfo Lutz Institute. The
sensitivity to detect anti-HAV IgM was 100% (95%CI: 79.1 to 100.0%), employing
saliva as clinical samples. In detecting anti-HAV IgA, the sensitivity was 80. 8%
(95%CI: 60.0 to 92.7%) and for the total antibodies was 82.1% (95%CI: 62.4 to
93.2%). The specificity was 100% for each. The rate of agreement was high
comparing the results of serum and saliva samples for detecting HAV antibodies.
We conclude that saliva is an acceptable alternative specimen for diagnosing
acute hepatitis A infection, and for screening individuals to receive hepatitis A
vaccine or immunoglobulin.

PMID: 10968882 [PubMed - indexed for MEDLINE]

742: Infection. 2000 Jul-Aug;28(4):231-3.

Association in the seroprevalence of hepatitis A and herpes simplex-1 viruses in 
young adults in Israel.

Katz J, Gdalevich M, Ashkenazi I, Chaushu G, Shemer J.

Israel Defence Force Medical Corps, Military, IDF. katzdr@internet-zahav.net

BACKGROUND: The rise in the standard of living of the Israeli population during
recent decades has been accompanied by a significant decline in the prevalence of
various viral diseases including hepatitis A (HAV). This trend is not reflected
in the seroprevalence of herpes simplex (HSV) infection, which has remained
stable during these years. MATERIALS AND METHODS: The Public Health Branch of the
Israel Defense Force (IDF) Medical Corps continuously draws a systematic,
representative sample of male and female recruits on their 1st day of service,
based on digit combinations of the military identification number. These recruits
are asked to give a blood sample and to undergo a short interview. A quantitative
determination of anti-HSV-1 and anti-HAV antibodies was performed. RESULTS: In
the present study that included 124 male and 98 female 18-year-old army recruits,
51.1% of the anti-HSV-positive subjects was also positive for anti-HAV, compared 
to 27% among anti-HSV-negative persons. Rate ratio (RR) for anti-HAV
seropositivity between anti-HSV-1-positive and negative recruits was 1.86 (95% CI
1.3-2.7). CONCLUSION: The present study suggests a strong association between the
seroprevalence of both viruses.

PMID: 10961530 [PubMed - indexed for MEDLINE]

743: Infection. 2000 Jul-Aug;28(4):205-8.

Ethnic and geographic variations in the prevalence of hepatitis A, B and C among 
aboriginal villages in Hualien, Taiwan.

Lin HH, Li YH, Yu JH, Wang YW, Lua AC, Huang LC, Huang SC, Lee ML.

Dept. of Gastroenterology, Buddhist Tzu Chi General Hospital, Hualien, Taiwan.
yoyo@tzuchi.org.tw

BACKGROUND: Taiwan is endemic for viral hepatitis infections. A field survey was 
performed in the isolated aborigines in Hualien, eastern Taiwan, to investigate
the geographic and ethnic variations in hepatitis epidemiology. MATERIALS AND
METHODS: From 1996 to 1998, blood was drawn from 1,748 subjects from two southern
Ami and two northern Atayal villages for serum markers of hepatitis A, B and C.
RESULTS: Hepatitis A infection approached 100% in all groups. Hepatitis B
infection and carrier rates were higher in the Atayal than in the Ami (92.3% vs. 
49.1% and 20.8% vs. 5.3%; p<0.01). Hepatitis C infection rates were higher in
three villages (27.5%, 20.1% and 25.4% vs. 3.6%; p<0.01). Hepatitis C infection
increased with age (p<0.01) while hepatitis B infection did not. CONCLUSION:
Hepatitis A infected most aborigines before the age of 15 years. Hepatitis B
seldom infected people after the age of 15 years, while hepatitis C continued to 
infect people who were older. Geographic factors are important for hepatitis C
infection, whereas for hepatitis B infection, in addition ethnicity is also
important.

Publication Types: 
    Research Support, U.S. Gov't, P.H.S.

PMID: 10961524 [PubMed - indexed for MEDLINE]

744: J Occup Environ Med. 2000 Aug;42(8):821-6.

Prevalence of antibody to hepatitis A virus in drinking water workers and
wastewater workers in Texas from 1996 to 1997.

Weldon M, VanEgdom MJ, Hendricks KA, Regner G, Bell BP, Sehulster LM.

Epidemic Intelligence Service, Epidemiology Program Office, Centers for Disease
Control and Prevention, Austin, TX, USA.

To determine if wastewater workers had a higher prevalence of antibody to
hepatitis A virus (anti-HAV) than drinking water workers, a convenience sample of
Texas wastewater and drinking water workers was evaluated for risk factors by
questionnaire and tested for anti-HAV. A total of 359 wastewater and 89 drinking 
water workers participated. Anti-HAV positivity was 28.4% for wastewater and
23.6% for drinking water workers. After adjustment for age, educational
attainment, and Hispanic ethnicity, the odds ratio for the association between
anti-HAV positivity and wastewater industry employment was 2.0 (95% confidence
interval, 1.0 to 3.8). Among wastewater workers, never eating in a lunchroom, >
or = 8 years in the wastewater industry, never wearing face protection, and skin 
contact with sewage at least once per day were all significantly associated with 
anti-HAV positivity in a model that adjusted for age and educational attainment. 
Wastewater workers in this study had a higher prevalence of anti-HAV than
drinking water workers, which suggested that wastewater workers may have been at 
increased risk of occupationally acquired hepatitis A. Work practices that expose
workers to wastewater may increase their risk.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 10953820 [PubMed - indexed for MEDLINE]

745: J Gastroenterol Hepatol. 2000 Jul;15(7):809-11.

Sensory neuropathy in the prodromal phase of hepatitis A and review of the
literature.

Islam S, McDonald JA.

Department of Gastroenterology, The Wollongong Hospital, NSW, Australia.

We report an unrecognized clinical presentation of hepatitis A with unilateral
peripheral acute sensory loss in the prodromal phase of the illness. Although
rare, focal neurological signs are known to occur in hepatitis A before, during
and after the icteric phase; a pure peripheral sensory neuropathy is distinctly
uncommon. Possible lesions could include radiculopathy of the lower
thoraco-lumbo-sacral dorsal nerve roots or a partial transverse myelitis of
Brown-Séquad like distribution. The signs and symptoms lasted only a few days and
the patient had an uneventful recovery.

Publication Types: 
    Case Reports
    Review

PMID: 10937691 [PubMed - indexed for MEDLINE]

746: Turk J Pediatr. 2000 Apr-Jun;42(2):105-8.

Clinical trial to evaluate immunogenicity and safety of inactivated hepatitis A
vaccination starting at 2-month-old children.

Kanra G, Yalçin SS, Ceyhan M, Yurdakök K.

Department of Pediatrics, Faculty of Medicine, Hacettepe University, Ankara,
Turkey.

Active immunization with hepatitis A vaccine has been shown to provide long-term 
protection against hepatitis A virus (HAV) infection. However, few data are
available regarding use of the hepatitis A vaccine in children under two years of
age. The present study was conducted to test the safety and immunogenicity of
inactivated hepatitis A vaccine administered to infants, and to evaluate the
correlation between mother and infant anti-HAV antibodies. A total of sixty
healthy children, two months of age, were enrolled in this study and immunized
with 360 EU of inactivated hepatitis A vaccine (Havrix) according to the two,
four and six months of age schedule. Blood sampling was performed prior to the
first vaccination and one month after the third vaccination at seven months.
Venipuncture was also done on mother on admission. The reactogenicity was
expressed as the percentage of reported local and systemic reactions. The most
common side effects were erythema on the injection site and fever. Infants with
passively transferred maternal anti-HAV antibodies had a reduced anti-HAV GMT
after vaccination. On admission, only one infant and his mother were seronegative
and seroconversion was only detected in this infant. One month after the third
dose seven infants (12.3%) were found to be seronegative. The infant without
passively acquired maternal anti-HAV had the protective levels with a GMT of 3176
mIU/ml one month following the third dose. There was a significant positive
correlation between the titers of mother and infant anti-HAV antibodies (n =
0.96, p < 0.001) on admission. Hepatitis A vaccine showed no immunogenicity in
infants with presence of maternal antibodies. Hepatitis A vaccine is safe but it 
should be used after the disappearance of maternal antibodies.

Publication Types: 
    Clinical Trial

PMID: 10936974 [PubMed - indexed for MEDLINE]

747: Toxicol Pathol. 2000 Jul-Aug;28(4):548-54.

Overexpression of Grb2 in inflammatory lesions and preneoplastic foci and tumors 
induced by N-nitrosodimethylamine in Helicobacter hepaticus-infected and
-noninfected A/J mice.

Diwan BA, Ramakrishna G, Anderson LM, Ramljak D.

Intramural Research Support Program, SAIC Frederick, National Cancer
Institute-Frederick Cancer Research and Development Center, Maryland 21702-1201, 
USA. bdiwan@mail.ncifcrf.gov

Growth factors bind to membrane receptor tyrosine kinases, resulting in
autophosphorylation and subsequent binding to proteins with SH2 domains,
including growth factor receptor-bound protein 2 (Grb2). Grb2 bridges receptors
to tyrosine kinase substrates such as SHC and SOS, which in turn facilitate the
activation of downstream signaling pathways, including Ras and mitogen-activated 
protein kinase (MAPK). Overexpression of Grb2 has been demonstrated in several
types of neoplasia but has not been investigated in liver tumorigenesis. Here we 
investigated Grb2 expression in liver lesions in N-nitrosodimethylamine
(NDMA)-treated Helicobacter hepaticus-infected and -noninfected A/J mice at 1
year of age. Previously, we reported (6) that infection promotes the development 
of these NDMA-initiated tumors. In controls, Grb2 immunostaining was absent from 
normal hepatic tissues, whereas the inflammatory lesions in infected livers were 
positive for cytoplasmic Grb2 in both hepatocytes and infiltrating leukocytes.
All preneoplastic foci (7 of 7), 15 of 27 adenomas, and 3 of 7 carcinomas were
positive for Grb2 by immunostaining in both infected and noninfected
NDMA-initiated livers. Involvement of Grb2 was confirmed by immunoblotting of
similarly infected mice at 9 to 18 months of age, showing a 2.5- to 3.3-fold
increase in Grb2 protein in infected livers (p < 0.05 compared with uninfected
controls) as well as in preneoplastic foci, adenomas, and carcinomas. These
livers also showed a 2.5- to 2.8-fold increase in total Ras protein. The results 
suggest that upregulation of Grb2 is an early event in liver carcinogenesis,
whether caused by the bacterial infection or by NDMA. Concomitant upregulation of
Ras p21 would ensure transmission of amplified signal from growth factors via
Grb2.

Publication Types: 
    Research Support, U.S. Gov't, P.H.S.

PMID: 10930041 [PubMed - indexed for MEDLINE]

748: Can J Public Health. 2000 May-Jun;91(3):168-70.

Fulminant hepatitis A in patients with chronic liver disease.

Lefilliatre P, Villeneuve JP.

Division of Hepatology, Centre Hospitalier Universitaire de Montréal, Québec.

Fulminant hepatitis is a rare complication of acute hepatitis A virus (HAV)
infection. We report three cases of fulminant hepatic failure with death due to
HAV infection in patients with pre-existing chronic liver disease. Data from the 
literature also indicate a high case fatality rate during HAV superinfection in
patients with chronic hepatitis B, particularly those with cirrhosis, and in
patients with alcoholic cirrhosis. In patients with chronic hepatitis C, results 
are conflicting with some reports indicating a high fatality rate of HAV
superinfection and others not, irrespective of the presence or absence of
cirrhosis. Based on our observations and this review of the literature, we
suggest that patients with chronic liver disease should be vaccinated against
hepatitis A.

Publication Types: 
    Case Reports
    Review

PMID: 10927841 [PubMed - indexed for MEDLINE]

749: Arch Pediatr Adolesc Med. 2000 Aug;154(8):763-70.

The cost-effectiveness of adolescent hepatitis A vaccination in states with the
highest disease rates.

Jacobs RJ, Margolis HS, Coleman PJ.

Capitol Outcomes Research Inc, 6188 Old Franconia Rd, Alexandria, VA 22310, USA. 
Jake.Jacobs@capitoloutcomesresearch.com.

BACKGROUND: The Advisory Committee on Immunization Practices has recommended
routine childhood hepatitis A vaccination in states and communities where the
incidence of disease exceeds the national average, but most adolescents are
currently unprotected from infection. OBJECTIVE: To estimate clinical and
economic consequences of vaccinating adolescents against hepatitis A in the 10
states with the highest disease rates. DESIGN: Decision analysis was used to
assess cost-effectiveness from societal and health system perspectives. Parameter
estimates were obtained from national surveillance data, a study of hepatitis A
cases, and an expert panel. MAIN OUTCOME MEASURES: Reduction in disease
incidence; costs of vaccination, treatment, and work loss; years of life saved
(YOLS); and costs per YOLS. RESULTS: In states with the highest disease rates,
vaccination of adolescents against hepatitis A would reduce the lifetime risk of 
symptomatic infection from 3.3% to 0.7% and prevent loss of 2117 years of life.
Vaccination of a single birth cohort would cost $30.9 million, yet treatment and 
work loss costs would decline $14.2 million and $23.8 million, respectively.
Hepatitis A vaccination would cost the health system $7902 per YOLS or $13,722
per discounted YOLS. Results are most sensitive to variation in the discount rate
and assumptions regarding long-term vaccine protective efficacy. CONCLUSIONS:
Hepatitis A vaccination of adolescents in states with high disease rates would
reduce costs to society. Although health system costs would increase,
cost-effectiveness is comparable to other recommended vaccines and superior to
many commonly used medical interventions. Arch Pediatr Adolesc Med.
2000;154:763-770

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 10922271 [PubMed - indexed for MEDLINE]

750: J Rheumatol. 2000 Jul;27(7):1792-5.

Hepatitis A infection mimicking adult onset Still's disease.

Sridharan S, Mossad S, Hoffman G.

Department of Rheumatic and Immunological Diseases, The Cleveland Clinic
Foundation, Ohio 44195, USA. sridhas@ccf.org

Fever, rash, and arthritis may be components of the prodrome of viral hepatitis. 
In the absence of jaundice and abnormal liver function tests, this form of
polyarthritis is easily confused with primary autoimmune diseases. Whereas the
association of systemic illness with musculoskeletal symptoms and numerous viral 
infections is well known, such an association with hepatitis A has only been
rarely reported. We describe a case of hepatitis A infection mimicking adult
onset Still's disease, and review the pathogenesis and differential diagnosis of 
Still's disease and the extraarticular manifestations of hepatitis.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't

PMID: 10914871 [PubMed - indexed for MEDLINE]

751: Am J Epidemiol. 2000 Jul 15;152(2):186-92.

Multiple modes of hepatitis A virus transmission among methamphetamine users.

Hutin YJ, Sabin KM, Hutwagner LC, Schaben L, Shipp GM, Lord DM, Conner JS,
Quinlisk MP, Shapiro CN, Bell BP.

Hepatitis Branch, Division of Viral and Rickettsial Disease, Centers for Disease 
Control and Prevention, Atlanta, GA 30333, USA.

Methamphetamine users are at increased risk of hepatitis A, but modes of
transmission are unclear. The authors conducted a case-control study among
methamphetamine users during an outbreak in Iowa in 1997. Twenty-eight reported, 
laboratory-confirmed, hepatitis A cases did not differ from 18 susceptible
controls with respect to age, sex, or number of doses used. When compared with
controls in multivariate analysis, case-patients were more likely to have
injected methamphetamine (odds ratio (OR) = 5.5, 95% confidence interval (CI):
1.1, 27), to have used methamphetamine with another case-patient (OR = 6.2, 95%
CI: 0.95, 41), and to have used brown methamphetamine (OR = 5.5, 95% CI: 0.51,
59). Receptive needle sharing was reported by 10 of the 20 case-patients who
injected. Methamphetamine use with another case-patient was also associated with 
hepatitis A in an analysis restricted to noninjectors (OR = 17, 95% CI: 1.0,
630). During this outbreak, hepatitis A may have been transmitted from person to 
person among methamphetamine users through the fecal-oral and the percutaneous
routes. Methamphetamine users should be vaccinated against hepatitis A and should
be given immune globulin if they used methamphetamine with a case-patient in the 
last 2 weeks. Persons who intend to continue using methamphetamine should be
advised about safer practices.

PMID: 10909956 [PubMed - indexed for MEDLINE]

752: Commun Dis Public Health. 2000 Jun;3(2):139-40.

Outbreak of hepatitis A in a special needs school in Kent: 1999.

Ang LH.

West Kent Health Authority, Aylesford. lihean.ang@wkent-ha.sthames.nhs.uk

In an outbreak of hepatitis A virus (HAV) infection in a special needs school
salivary testing was used to identify those recently infected and those who were 
immune. The value of such testing as an epidemiological and outbreak control tool
is discussed. HAV vaccine rather than human normal immunoglobulin was used to
bring the outbreak under control.

PMID: 10902260 [PubMed - indexed for MEDLINE]

753: J Infect Dis. 2000 Jul;182(1):12-7. Epub 2000 Jun 27.

Duration of viremia in hepatitis A virus infection.

Bower WA, Nainan OV, Han X, Margolis HS.

Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.
wbower@cdc.gov

The duration of viremia and time course for development of IgM antibodies were
determined prospectively in natural and experimental hepatitis A virus (HAV)
infection. Serial serum samples from HAV-infected men (n=13) and experimentally
infected chimpanzees (n=5) were examined by nested reverse-transcriptase
polymerase chain reaction analysis to detect HAV RNA and by ELISA to detect IgM
antibodies to HAV. Among infected humans, HAV RNA was detected an average of 17
days before the alanine aminotransferase peak, and viremia persisted for an
average of 79 days after the liver enzyme peak. The average duration of viremia
was 95 days (range, 36-391 days). Results were similar in chimpanzees. In
addition, HAV RNA was detected in serum of humans and chimpanzees several days
before IgM antibodies to HAV were detected. These results indicate that adults
with HAV infection are viremic for as long as 30 days before the onset of
symptoms and that the duration of viremia may be longer than previously
described.

PMID: 10882576 [PubMed - indexed for MEDLINE]

754: Trop Gastroenterol. 2000 Apr-Jun;21(2):63-5.

Age related seroprevalence of antibodies to hepatitis A virus in Hyderabad,
India.

Joshi N, Yr NK, Kumar A.

Department of Gastroenterology, Nizam's Institute of Medical Sciences,
Panjagutta, Hyderabad.

BACKGROUND: Hepatitis A virus (HAV) is an enterically transmitted viral disease
endemic in many developing countries including India. Infection is often
subclinical or asymptomatic in children while with increasing age symptomatic
acute infections are more common. In some developing countries improvements in
living conditions have led to change in epidemiology of HAV infection. In our
country there are very few reports on prevalence of HAV. OBJECTIVE: The present
study was undertaken to determine the seroprevalence of hepatitis A virus
antibodies in relation to age in Hyderabad. MATERIAL AND METHODS: Serum samples
were collected from 90 subjects in the age group 2-64 years in a mass vaccination
camp for Hepatitis B. All the subjects were investigated with a uniform social
and medical history questionnaire. Sera were tested for antibody to HAV (total
anti-HAV) using enzyme immunoassay (General Biologicals, Taiwan). RESULTS: The
subjects included 48 males and 42 females. There were 54 children (< 12 yrs) and 
36 adults. Of the 90 serum samples tested 51 (56%) were positive for anti HAV
antibodies. The seropositivity in males and females was similar. The
seroprevalence was 31.8% (17/54) in children (< 12 years) and 94.4% (34/36) in
adults (p < 0.001). Age related seroprevalence revealed that a majority of
children below 10 years (33/48, 69%) remain anti HAV negative, while only 25% of 
children below 15 years were anti HAV negative. The anti HAV antibody positivity 
was similar in different income groups. CONCLUSION: The prevalence of HAV is high
in Hyderabad. A majority of children below 10 years and 25% of children < 15
years remain susceptible to HAV infection. Child immunization against HAV
therefore should be considered in our population too.

PMID: 10881625 [PubMed - indexed for MEDLINE]

755: Appl Environ Microbiol. 2000 Jul;66(7):2759-63.

Contamination of foods by food handlers: experiments on hepatitis A virus
transfer to food and its interruption.

Bidawid S, Farber JM, Sattar SA.

Health Canada, Food Directorate, Bureau of Microbial Hazards, Ottawa, Ontario,
Canada K1A 0L2. Sabah_Bidawid@hc-sc.gc.ca

Hepatitis A virus (HAV) is an important pathogen which has been responsible for
many food-borne outbreaks. HAV-excreting food handlers, especially those with
poor hygienic practices, can contaminate the foods which they handle. Consumption
of such foods without further processing has been known to result in cases of
infectious hepatitis. Since quantitative data on virus transfer during contact of
hands with foods is not available, we investigated the transfer of HAV from
artificially contaminated fingerpads of adult volunteers to pieces of fresh
lettuce. Touching the lettuce with artificially contaminated fingerpads for 10 s 
at a pressure of 0.2 to 0.4 kg/cm(2) resulted in transfer of 9.2% +/- 0.9% of the
infectious virus. The pretreatments tested to interrupt virus transfer from
contaminated fingerpads included (i) hard-water rinsing and towel drying, (ii)
application of a domestic or commercial topical agent followed by water rinsing
and towel drying, and (iii) exposure to a hand gel containing 62% ethanol or 75% 
liquid ethanol without water rinsing or towel drying. When the fingerpads were
treated with the topical agents or alcohol before the lettuce was touched, the
amount of infectious virus transferred to lettuce was reduced from 9.2% to
between 0.3 and 0.6% (depending on the topical agent used), which was a reduction
in virus transfer of up to 30-fold. Surprisingly, no virus transfer to lettuce
was detected when the fingerpads were rinsed with water alone before the lettuce 
was touched. However, additional experiments with water rinsing in which smaller 
volumes of water were used (1 ml instead of 15 ml) showed that the rate of virus 
transfer to lettuce was 0.3% +/- 0.1%. The variability in virus transfer rates
following water rinsing may indicate that the volume of water at least in part
influences virus removal from the fingerpads differently, a possibility which
should be investigated further. This study provided novel information concerning 
the rate of virus transfer to foods and a model for investigating the transfer of
viral and other food-borne pathogens from contaminated hands to foods, as well as
techniques for interrupting such transfer to improve food safety.

PMID: 10877765 [PubMed - indexed for MEDLINE]

756: Am J Med Sci. 2000 Jun;319(6):417-9.

Acute hepatitis A: combination of the relapsing and the cholestatic forms, two
rare variants.

Rachima CM, Cohen E, Garty M.

Recanati Center for Medicine and Research, Rabin Medical Center, Petach-Tikva,
Israel.

Here we present an unusual case of a 23-year-old, otherwise healthy man who had a
biphasic form of viral hepatitis A with a combination of two variants, the
relapsing and cholestatic forms. One month after resolution of the first phase of
acute hepatitis A, he was readmitted with jaundice and intense pruritus. During
hospitalization, his serum bilirubin level increased to 50.2 mg/dL, with a slight
increase in the other levels of liver enzymes. He was treated with
ursodeoxycholic acid and later with corticosteroid therapy, resulting in
resolution of symptoms and improvement of his liver function tests after 2 weeks.
Medication therapy seems to be justified in markedly symptomatic patients with
relapsing hepatitis.

Publication Types: 
    Case Reports

PMID: 10875301 [PubMed - indexed for MEDLINE]

757: J Viral Hepat. 2000 May;7 Suppl 1:23-5.

Hepatitis C and the British Columbia experience with hepatitis A vaccination.

Daly P.

Communicable Disease Control, Vancouver/Richmond Health Board, Canada.

The prevalence of hepatitis C virus (HCV) infection in British Columbia is
approximately 1.5%. Experience in this province has revealed that groups at high 
risk of HCV infection are also prone to outbreaks of hepatitis A virus (HAV). As 
hepatitis A infection can be fatal in HCV-positive individuals, numerous
strategies have been implemented to help minimize its spread. The importance of
vaccinating individuals at high risk for hepatitis C infection against HAV has
been recognized.

PMID: 10870176 [PubMed - indexed for MEDLINE]

758: J Viral Hepat. 2000 May;7 Suppl 1:15-7.

Hepatitis A in patients with chronic liver disease - severity of illness and
prevention with vaccination.

Keeffe E.

Stanford University School of Medicine, Division of Gastroenterology, Liver
Transplant Program, Stanford University Medical Centre, Stanford, CA 94304-1509, 
USA.

Acute hepatitis A in patients with pre-existing chronic liver disease (CLD) may
theoretically predispose such patients to a more severe outcome of infection. The
results of reports covering epidemics and case series suggest but do not
universally support this possibility. An analysis of the larger case series
support the suggestion that acute hepatitis A superimposed on chronic hepatitis B
infection is associated with higher peak laboratory abnormalities, more severe
disease and a higher fatality rate. The safety and immunogenicity of an
inactivated hepatitis A vaccination was evaluated in patients with CLD and found 
to be satisfactory for the protection of this group of patients.

Publication Types: 
    Review

PMID: 10870175 [PubMed - indexed for MEDLINE]

759: J Viral Hepat. 2000 May;7 Suppl 1:1-3.

What did we learn from the Shanghai hepatitis A epidemic?

Cooksley WG.

Royal Brisbane Hospital Research Foundation and University of Queensland,
Brisbane, Australia.

A major outbreak of hepatitis A (HAV), associated with consumption of raw clams, 
occurred in Shanghai, China in 1988. Over 300 000 cases were reported, of which
47 (0.015%) were fatal. An elevated mortality rate was observed in hepatitis B
surface antigen (HBsAg)-positive patients (0.05%). The majority of these patients
were also hepatitis B e antigen (HBeAg)-positive, indicating active liver disease
and high viral replication rates. The increased mortality in hepatitis B virus
(HBV)/HAV coinfected individuals is hypothesized to be the result of
T-cell-mediated destruction of HBV-infected hepatocytes, enhanced by acute HAV
infection. Following recovery from HAV there is an increase in HBV expression and
activated cytotoxic cells and subsequent cytolysis. Patients with chronic HBV
infection are clearly at considerable risk of severe disease and increased
mortality in the event of HAV infection. The period of greatest risk is during
the immunoeliminative phase of HBV infection, which generally occurs in early
adulthood. With the prevalence of HBV approaching 10% in this group, there is a
clear opportunity for benefit from vaccination.

Publication Types: 
    Review

PMID: 10870174 [PubMed - indexed for MEDLINE]

760: J Viral Hepat. 2000 May;7 Suppl 1:29-30.

Consensus statement on the role of hepatitis A vaccination in patients with
chronic liver disease.

Cooksley WG.

Royal Brisbane Hospital Research Foundation and University of Queensland,
Brisbane, Australia.

Hepatitis A virus (HAV) is a ubiquitous, easily transmitted virus that can cause 
severe hepatitis, particularly in the adult population. Improvements in
sanitation and hygiene in the developing world have led to a decline in immunity 
against HAV. A growing number of adults are now susceptible to infection, with
those who have not been vaccinated against hepatitis B virus (HBV) being at risk 
of dual infection and potentially more severe illness. The symposium, "The role
of hepatitis vaccination in patients with chronic liver disease", provided the
opportunity to develop a consensus statement. It was concluded that patients with
non-viral chronic liver disease (CLD) and certain groups with HBV infection can
develop more severe disease in the event of HAV infection. It was identified that
patients with CLD should be targeted for hepatitis A vaccination as soon as CLD
is diagnosed.

PMID: 10866843 [PubMed - indexed for MEDLINE]

761: J Viral Hepat. 2000 May;7 Suppl 1:27-8.

Epidemiology of hepatitis A in Asia and experience with the HAV vaccine in Hong
Kong.

Sung JJ.

Division of Gastroenterology and Hepatology, Department of Medicine, Prince of
Wales Hospital, Chinese University of Hong Kong, Shatin, New Territories, Hong
Kong.

Hepatitis A and hepatitis B infections are prevalent throughout Asia. Patients
infected with hepatitis B virus (HBV) have a higher morbidity and mortality if
superinfected with hepatitis A virus (HAV). In Hong Kong, adolescents and young
adults are particularly prone to severe hepatitis infection. Hepatitis A
vaccination of patients with or without chronic HBV infection has been shown to
be efficacious and associated with a good safety profile.

Publication Types: 
    Review

PMID: 10866842 [PubMed - indexed for MEDLINE]

762: J Viral Hepat. 2000 May;7 Suppl 1:19-21.

Hepatitis A vaccination in patients with chronic liver disease in Taiwan.

Lee S.

Department of Medicine, Veterans General Hospital-Taipei, and National Yang-Ming 
University School of Medicine, Taipei, Taiwan, Republic of China.

While hepatitis A infection is rarely fatal, mortality is age-dependent,
suggesting that cofactors may play a role in disease expression. The safety and
immunogenicity of an inactivated hepatitis A vaccine was evaluated in a study
involving 60 patients with chronic liver disease (CLD) (56 patients with chronic 
hepatitis B, and four patients with chronic hepatitis C). A two-dose schedule, at
0 and 6 months, produced 100% seroconversion. All individuals remained
seropositive for 12 months, the majority maintaining high levels of antibody
during a 5-year follow-up period. The inactivated hepatitis A vaccine was found
to be well tolerated and immunogenic in patients with CLD. However, the immune
response generated was inferior to that observed in healthy individuals,
indicating the need for a higher dose, and the two-dose schedule to ensure
adequate protection.

Publication Types: 
    Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 10866841 [PubMed - indexed for MEDLINE]

763: J Viral Hepat. 2000 May;7 Suppl 1:11-2.

Acute hepatitis A and acquired immunity to hepatitis A virus in hepatitis B virus
(HBV) carriers and in HBV- or hepatitis C virus-related chronic liver diseases in
Thailand.

Pramoolsinsap C.

Gastrointestinal Unit, Ramathibodi Hospital and Faculty of Medicine, Mahidol
University, Bangkok, Thailand.

A number of studies have suggested that the clinical course of hepatitis A virus 
(HAV) infection is more severe in patients with chronic liver disease (CLD). A
study was undertaken to determine the impact of acute HAV in asymptomatic
hepatitis B surface antigen (HBsAg) carriers (n = 20) and patients with hepatitis
B virus (HBV)-(n = 8) or hepatitis C virus (HCV)-related (n = 4) CLD. Disease
progression was compared with that in 100 patients with isolated HAV infection.
No patient with HAV infection alone developed complications, and all recovered
fully. Fulminant or submassive hepatitis occurred in 55% of HBsAg carriers and
33% of patients with HBV- or HCV-related CLD. The mortality rate in HBsAg
carriers (25%) was not significantly different from that in the patients with CLD
(33%). The seroprevalence of anti-HAV immunoglobulin G in 820 individuals was
also determined. Approximately 50% of the individuals had acquired HAV infection 
between the ages of 21 and 30 years. It was demonstrated that HAV infection may
have a more severe clinical course in patients with underlying CLD, particularly 
among older individuals. Vaccination for such patients should be considered.

Publication Types: 
    Review

PMID: 10866839 [PubMed - indexed for MEDLINE]

764: J Viral Hepat. 2000 May;7 Suppl 1:9-10.

Fulminant hepatitis in patients with chronic liver disease.

O'Grady JG.

Liver Unit, King's College Hospital, Denmark Hill, London, UK.

The changing epidemiology of hepatitis A virus (HAV) in the UK has led to a
decline in natural immunity against the virus. It is estimated that in the UK,
HAV is responsible for 10%-20% of cases of liver failure, and an overall
mortality rate of 0.1%. It is clear that certain factors predispose patients to
more severe HAV disease and increased mortality, although the reasons for this
have yet to be elucidated. The age at which infection occurs clearly influences
the outcome, with the risk of severe hepatitis increasing sharply after the age
of 40 years. Intravenous drug users, homosexual men, individuals with an
excessive alcohol intake or patients with chronic liver disease are also at
increased risk of severe disease. An analysis of data from King's College
Hospital was performed to determine the factors that influence the outcome or
clinical course of HAV infection in at-risk patients. Data compiled from 1991 to 
1998 revealed 187 cases with confirmed HAV, 45 of whom developed severe
hepatitis. Outcomes were varied, eight (17.7%) patients developed acute liver
failure and two (4.4%) died.

Publication Types: 
    Review

PMID: 10866838 [PubMed - indexed for MEDLINE]

765: J Viral Hepat. 2000 May;7 Suppl 1:7-8.

Fulminant hepatitis associated with hepatitis A virus superinfection in patients 
with chronic hepatitis C.

Vento S.

Department of Infectious Diseases, University of Verona, Verona, Italy.
vento@borgotrento.univr.it

There have been conflicting reports of the clinical outcome of acute hepatitis A 
virus (HAV) infection in patients with chronic hepatitis C virus (HCV) infection.
A prospective study evaluated 432 patients with chronic hepatitis C (183 with
cirrhosis) over a 7-year period. Of the 17 patients with concurrent HAV
infection, seven developed fulminant hepatitis and six died. None of these
patients had cirrhosis; however, the HLA phenotype (A1; B8:DR3) appeared to be a 
significant factor in the development of fulminant hepatitis. Patients with this 
phenotype had high titres of antinuclear antibodies, antismooth muscle antibodies
and antiasialoglycoprotein-receptor antibodies, possibly reflecting the induction
of autoimmune hepatitis in this group. The high frequency of fulminant hepatitis 
in patients with HAV/HCV coinfection contrasts with other surveys, although a
large Centers for Disease Control and Prevention (CDC) survey demonstrated that
HAV infection in patients with pre-existing chronic liver disease (CLD) is
associated with increased mortality. It is likely that CLD has some importance as
an underlying factor in the development of fulminant hepatitis following HAV
infection. Further prospective studies are needed to clarify this issue.

Publication Types: 
    Review

PMID: 10866837 [PubMed - indexed for MEDLINE]

766: J Viral Hepat. 2000 May;7 Suppl 1:5-6.

A virological perspective on the need for vaccination.

Locarnini S.

Research and Molecular Development, Victorian Infectious Diseases, Reference
Laboratory, North Melbourne, Victoria, Australia.

Superinfecton of chronic carriers of hepatitis B virus (HBV) or hepatitis C virus
(HCV) with hepatitis A virus (HAV) is often associated with more severe liver
disease than infection with HAV alone. Superinfection commonly causes markers of 
HBV and HCV replication to fall to significantly lower levels. The pathogenesis
of acute liver damage characteristic of viral hepatitis is thought to be mediated
by host cytotoxic T-lymphocytes (CTLs) directed against virus-infected
hepatocytes. It has been proposed that the more aggressive liver disease observed
in individuals infected with HAV in addition to chronic HBV/HCV is a result of
the induction of interferon (IFN)-alpha during acute HAV infection. This accounts
for the antiviral effect on the active markers of HBV/HCV replication, and the
enhanced CTL response against HBV/HCV-infected hepatocytes. Alternatively, HAV
may indirectly stimulate the T helper 1 (Th1)-type cytokine responses, such as
interleukin (IL)-2, IFN-gamma and tumour necrosis factor (TNF)-alpha, which
directly promote the antiviral CTL response. Clearance of HBV infection, and
possible HAV and HCV, is associated with a specific CTL response, while viral
persistence in chronic HBV and HCV infection has been attributed to an imbalance 
in the Th1-Th2 arms of the immune response. Vaccination against hepatitis A
should be considered for patients with chronic HBV/HCV infection, to minimize the
risk of exacerbating underlying liver disease.

Publication Types: 
    Review

PMID: 10866836 [PubMed - indexed for MEDLINE]

767: Antivir Ther. 2000 Mar;5(1):15-7.

Persisting HIV-1 replication triggered by acute hepatitis A virus infection.

Ridolfo AL, Rusconi S, Antinori S, Balotta C, Galli M.

Institute of Infectious Diseases and Tropical Medicine, Luigi Sacco Hospital,
University of Milan, Italy.

We report the case of two patients in whom acute hepatitis A was associated with 
a marked and prolonged increase in human immunodeficiency virus type 1 (HIV-1)
viral load. Although in one patient the rise in HIV-1 RNA might also have been
related to the interruption of antiretroviral therapy, we also observed a similar
pattern in the other patient who had a stable undetectable plasma viraemia prior 
to acute hepatitis and never received treatment with anti-retrovirals. Our
observation supports the hypothesis that immune activation that is induced by
acute hepatitis A virus (HAV) infection may trigger HIV-1 replication. This
highlights the importance of maintaining antiretroviral therapy throughout the
acute phase of hepatitis A and of preventing HAV infection through active
immunization.

Publication Types: 
    Case Reports

PMID: 10846587 [PubMed - indexed for MEDLINE]

768: Trop Doct. 2000 Apr;30(2):99-101.

Hepatitis A seroprevalence rate in Syria.

Antaki N, Kebbewar MK.

Gastroenterology Department, Saint Louis Hospital, Syria.

Hepatitis A is a benign infection, which in the developing world affects mainly
children; the majority of adults are immune by the age of 30. In the last decade 
or so, a shift in the prevalence pattern of hepatitis A virus (HAV) infection
from a low- to a high-age group has appeared in the developed countries. This
shift has been attributed to an improvement in the socio-economic and hygienic
conditions. In the present study, 849 Syrians of all age groups and both sexes
were tested by enzyme-linked immunosorbent assay technique for the seroprevalence
of hepatitis A IgG antibody (anti-HAV IgG). It was observed that anti-HAV IgG was
present in 89% Syrian population; with 50% in the 1-5 year age group and 95% in
the 11-15 year age group. These results demonstrate that HAV infection in Syria
is mostly acquired during childhood. As yet there is no serological evidence of a
shift in HAV infection from a younger to a higher age group.

PMID: 10842558 [PubMed - indexed for MEDLINE]

769: Indian J Pediatr. 2000 Feb;67(2):77-9.

Seroepidemiology of hepatitis A in Delhi.

Dutta AK, Aggarwal A, Kapoor AK, Ray GN, Batra S.

Department of Pediatrics, Kalawati Saran Children's Hospital, Lady Hardinge
Medical College, New Delhi.

A prospective study was done to determine the age specific prevalence of
antihepatitis A antibodies (anti HAV Abs) among children in Delhi. Four hundred
and twenty children aged 0-12 years attending outpatient department for
vaccination or any minor illness were studied. Sera was tested by ELISA for anti 
HAV Abs using a commercial kit (Hepvase A 96 TMB). Thirty samples of cord blood
were similarly analyzed. All samples of cord blood were positive for anti HAV
Abs. Prevalence of anti HAV Abs was 80% by 5 years of age. The most vulnerable
age group was 0.5-1.5 years (anti HAV Ab positivity). Cord blood had 100%
positivity. Univariate and multivariate analyses taking anti HAV antibody
positivity as dependant variable demonstrated that age and father's education
(socioeconomic status) significantly affect prevalence of anti HAV Abs. Sex,
water supply, history of jaundice in self or family did not have any significant 
effect on anti HAV antibody positivity. Prevalence of anti HAV antibodies is 80% 
by 5 years of age. Further studies in different strata of society and different
regions in the country are required to assess the need and age for vaccination.

PMID: 10832229 [PubMed - indexed for MEDLINE]

770: Dermatology. 2000;200(3):266-9.

Photo-accentuated eruption and vascular deposits of immunoglobulin A associated
with hepatitis A virus infection.

Kano Y, Kokaji T, Shiohara T.

Department of Dermatology, Kyorin University School of Medicine, Tokyo, Japan.

Skin rash associated with hepatitis A virus infection has rarely been reported.
We describe a patient with hepatitis A virus infection who presented a
rubelliform rash markedly accentuated in sun-exposed areas; direct
immunofluorescence studies of the lesion revealed immunoglobulin (Ig) A
deposition on the endothelial cells in the upper dermis. Oral rechallenge tests
of the previously administered drugs failed to reproduce the eruption. The
preferential setting of immune complexes containing IgA at sites of sun exposure 
and sunlight as a triggering factor might have been responsible for the
development of the eruption in this patient. Eruptions associated with hepatitis 
A virus infections may be more frequent than commonly thought. Because of
difficulty to exclude the possibility of drug eruptions, these cases might have
been overlooked. In patients with such a disorder, a careful clinical workup such
as IgM antibodies for hepatitis A virus at diagnosis and during follow-up is
especially recommended. Copyright 2000 S. Karger AG, Basel.

Publication Types: 
    Case Reports

PMID: 10828640 [PubMed - indexed for MEDLINE]

771: Vaccine. 2000 Jul 1;18(26):3005-10.

Active versus passive immunization against hepatitis A in the Israel defence
forces: a cost-benefit analysis.

Gillis D, Yetiv N, Gdalevich M, Mimouni D, Ashkenazi I, Shpilberg O, Eldad A,
Shemer J.

Army Health Branch, Israel Defence Forces, Tel-Hashomer, Israel.
dgillis@netvision.net.il

We compared cost-benefit and cost-effectiveness analyses of hepatitis A
prevention with immune serum globulin (ISG) vs inactivated hepatitis A vaccine
(iHAV) in the Israel Defence Forces. Personnel were grouped according to
conditions and duration of service and analyses were performed based on maximum
and minimum hepatitis A projected incidences for each group. For standing army
soldiers in field units, iHAV is economically superior compared with ISG. For the
five other groups studied, the reverse is true. Expected increases in production 
costs of ISG and expected decreases in costs of iHAV are likely to make iHAV more
economical in the future.

PMID: 10825603 [PubMed - indexed for MEDLINE]

772: Epidemiol Infect. 2000 Apr;124(2):309-13.

A community outbreak of hepatitis A in a religious community in Indiana: failure 
of immune serum globulin to prevent the spread of infection.

Aszkenasy OM.

Community Child Health Department, West Lane Hospital, Middlesbrough.

An outbreak of hepatitis A occurred in a religious community in Indiana, USA.
Sixty-nine cases were ascertained among the 4466 residents over a year, and the
highest attack rate was in children. The management of the outbreak included the 
widespread use of prophylactic immune serum globulin (ISG). Despite this, further
cases occurred. To guide further ISG administration, a survey was undertaken to
ascertain what proportion remained susceptible to HAV infection. From a random
sample of 600 people in the affected community 440 saliva specimens (73%) were
obtained. Of these, 12.5% were found to be immune (95% confidence intervals from 
9-16%). No changes were made to the ISG administration policy. There was no
evidence to suggest that administration of ISG had any effect on the duration of 
the outbreak. There was a low rate of symptomatic infection among young children 
(less than 10 years); as ISG does not prevent the spread of the virus its use is 
not recommended in future outbreak situations.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 10813157 [PubMed - indexed for MEDLINE]

773: Dev Biol (Basel). 2000;102:29-35.

Non-enveloped viruses transmitted by blood and blood products.

Robertson BH, Erdman DD.

Hepatitis Branch A-33, Centers for Disease Control and Prevention, Atlanta, GA
30333, USA.

Since the advent of solvent detergent (S-D) treatment for inactivation of
enveloped viruses, there has been no transmission of human immunodeficiency
virus, hepatitis B virus, or hepatitis C virus by treated blood products.
However, shortly after the introduction of S-D treatment, transmission of
hepatitis A with S-D treated factor concentrates was reported in Germany, Italy, 
Ireland, the United States and South Africa, and this raised awareness of the
potential for blood transmission of non-enveloped viruses in general. This report
summarizes the physical and epidemiological features of three non-enveloped
viruses, hepatitis A virus, parvovirus B19, and the recently identified TT virus,
and their transmission by blood and blood products.

Publication Types: 
    Review

PMID: 10794088 [PubMed - indexed for MEDLINE]

774: Exp Toxicol Pathol. 2000 Mar;52(1):3-10.

Inducible nitric oxide synthase (iNOS) expression in liver and splenic T
lymphocyte rise are associated with liver histological damage during experimental
hepatitis A virus (HAV) infection in Callithrix jacchus.

Pinto MA, Marchevsky RS, Pelajo-Machado M, Santiago MA, Pissurno JW, França MS,
Baptista ML, Gouvea AS, Santana AA, Bertho AL, Schatzmayr HG, Gaspar AM, Kubelka 
CF.

Department of Virology, IOC/FIOCRUZ, Rio de Janeiro, Brazil.
marcelo@gene.dbbm.fiocruz.br

Callithrix jacchus is considered a reliable animal model for hepatitis A virus
(HAV) infection. All three HAV orally inoculated marmosets developed hepatitis - 
the infection was monitored by continuous virus shedding, high levels of serum
enzyme alanine aminotransferase, specific antibody and seroconversion 3-6 weeks
after HAV inoculation. HAV antigen was detected in liver by immunofluorescence 4 
days post inoculation (PI) and onwards. To gain insight into the biological role 
of inducible nitric oxide synthase (iNOS) during immune-related acute liver
injury the enzyme was searched in frozen biopsies: immunofluorescent labeling was
found in the cytoplasm of liver cells mainly Kupffer's cells and spleen
macrophages (CD68+) starting 11 days PI with maximum intensity on the fifth to
sixth week PI. Necroinflammatory liver lesions characteristic of viral hepatitis 
were also observed at 10 days PI with maximum severity at 4 to 6 weeks PI.
Furthermore, T lymphocytes (CD2+) were raised at this time point. No difference
was evident in the frequency of B lymphocytes (CD20+). Therefore, iNOS expression
preceded necroinflammatory liver lesion and maximal immunofluorescence reaction
was coincident with tissue injury, supporting the hypothesis that NO contributes 
to hepatic cytotoxic mechanism but also to virus clearance. The concomitant rise 
in T-lymphocyte population may suggest a role for these cells in this and/or
other independent HAV-induced pathological changes.

PMID: 10779146 [PubMed - indexed for MEDLINE]

775: Pediatr Clin North Am. 2000 Apr;47(2):395-406, vii.

Current update of pediatric hepatitis vaccine use.

Malay S, Tizer K, Lutwick LI.

Department of Pediatrics, SUNY-Health Science Center at Brooklyn, USA.

Vaccines are now available for the prevention of hepatitis A and hepatitis B. In 
this article, biologics are reviewed with special attention to their use in the
pediatric patient. Special attention is paid to issues that developed in 1999.
For hepatitis A vaccine, it is the change in US recommendations regarding
increased use in higher-risk US locations. For hepatitis B vaccine, it is the
concern about toxicity, real or imagined.

Publication Types: 
    Review

PMID: 10761510 [PubMed - indexed for MEDLINE]

776: Commun Dis Public Health. 2000 Mar;3(1):60-2.

Outbreak of hepatitis A spread by contaminated drinking glasses in a public
house.

Sundkvist T, Hamilton GR, Hourihan BM, Hart IJ.

Infektionsklinikens Mottagning, Boden, Sweden. torbjorn.sundkvist@nll.se

Ten cases of hepatitis A were associated with a public house whose barman had
chronic non-infectious diarrhoea and had served drinks while incubating hepatitis
A himself. Eight cases had drunk in the public house in the two weeks before the 
barman became ill, had no other risk factors for hepatitis A infection, and were 
regarded as primary cases. Two other cases had visited the pub during the same
period, but were classified as secondary cases because they became ill later and 
were contacts of primary cases. Sexual transmission was excluded. Fomite
transmission by contamination of glasses was a more likely route of spread of the
infection among the eight primary cases than food or contaminated surfaces in the
toilet.

PMID: 10743322 [PubMed - indexed for MEDLINE]

777: Arch Environ Health. 2000 Jan-Feb;55(1):7-10.

Risk of hepatitis A virus infection among sewage workers in Israel.

Levin M, Froom P, Trajber I, Lahat N, Askenazi S, Lerman Y.

Epidemiology Unit, Occupational Health and Rehabilitation Institute, Raanana,
Israel.

Sewage workers are exposed to a wide range of chemicals and biological agents,
including the hepatitis A virus. Inasmuch as Israel is an endemic area for
hepatitis A, it is unclear if sewage workers are at increased risk for hepatitis 
A or which factors contribute to such risk. The authors compared seropositivity
of hepatitis A in 100 sewage workers with that in 100 blue-collar worker
controls. Hepatitis A seropositivity was highly prevalent, but nonsignificant, in
both sewage workers and controls (82% and 91%, respectively). In sewage workers, 
the major risk for serological positivity was age (odds ratio = 4.5, 95%
confidence interval = 1.6, 12.4 for every 10 y). The factors associated
negatively with seropositivity were years of education and years of seniority.
The authors concluded that exposure to sewage is not a risk factor for hepatitis 
A infection in Israel, and, therefore, sewage workers do not require special
attention in this regard.

Publication Types: 
    Comparative Study

PMID: 10735513 [PubMed - indexed for MEDLINE]

778: Hepatology. 2000 Apr;31(4):834-9.

Comment in:
    Hepatology. 2000 Oct;32(4 Pt 1):873-4; author reply 874-5.    Hepatology. 2000 Oct;32(4 Pt 1):873; author reply 874-5.

The cost-effectiveness of hepatitis A vaccination in patients with chronic
hepatitis C.

Myers RP, Gregor JC, Marotta PJ.

Department of Medicine, Division of Gastroenterology, London Health Sciences
Centre, University of Western Ontario, London, Ontario, Canada.

Infection with hepatitis A virus (HAV) occasionally leads to acute liver failure 
and has a higher fatality rate in patients with chronic hepatitis C virus (HCV). 
Vaccination of patients with HCV against HAV is effective and well tolerated.
This study examines the cost-effectiveness of HAV vaccination in North American
patients with chronic HCV. A decision analysis model was constructed to compare 3
HAV vaccination strategies in adult patients with chronic HCV over a period of 5 
years: (1) vaccinate no patients (treat none); (2) vaccinate only susceptible
(anti-HAV negative) patients (selective); or (3) vaccinate all patients without
prior testing of immune status (universal). Probabilities and direct costs were
estimated from hospital data and the literature. The cost per patient for the 3
vaccination strategies were: treat none, $2.00; selective, $56.00; and universal,
$82.00. For every 1,000,000 patients with HCV vaccinated over a 5-year period,
the selective strategy prevented 128 symptomatic cases of HAV, 3 liver
transplantations, and 3 deaths owing directly to HAV compared with the treat none
strategy. In addition, the selective strategy costs an additional $427,000 per
patient with HAV prevented, and $23 million per HAV-related death averted,
compared with the treat none strategy. The results were most sensitive to the
incidence of HAV infection; vaccination increased costs if the annual rate of
infection was less than 0.56% (baseline, 0.01%). Vaccination of North American
patients with chronic HCV against HAV infection is not a cost-effective therapy.

PMID: 10733536 [PubMed - indexed for MEDLINE]

779: Yonsei Med J. 2000 Feb;41(1):34-9.

The changing epidemiology of hepatitis A in children and the consideration of
active immunization in Korea.

Sohn YM, Rho HO, Park MS, Park JH, Choi BY, Ki M, Jang WI.

Department of Pediatrics, Yonsei University College of Medicine, Seoul, Korea.
youngmo@yumc.yonsei.ac.kr

Currently, Korea is a low endemicity country for HAV, especially in children.
However, recent reports of hepatitis A outbreaks show that there has been a shift
of disease incidence to adolescents and young adults, with 2 cases of acute liver
failure in one reported outbreak. We need to study the immune status for HAV in
order to provide information for the establishment of preventive measures and
possible consequences of HAV in Korea. A total of 334 infants, children and
adolescents less than 20 years of age living in rural areas of Kyonggi Province, 
Korea were evaluated for anti-HAV immune status in 1996. Five hundred and
eighty-four primary school children living in the same area were separately
evaluated for the natural seroconversion rate between 1993 and follow-up samples 
taken in 1996. Anti-HAV IgG antibody was measured by enzyme immunoassay (HAVAB
EIA kit, Abbott Laboratories, Chicago, Illinois, USA). In comparison with
previous reports of seroprevalence rates, our data confirmed a dramatic drop in
seroprevalence rates among children and adolescents under 20 years of age living 
in rural areas, from over 63.8% two decades ago to 4.6% in 1996. Natural
acquisition of HAV antibody in primary school children rarely occurs, registering
only 0.5% during three years. Several outbreaks in young adults during 1996-1998 
suggested that immunity against HAV in this population is so low that massive
outbreaks are unavoidable. Teenagers and young adults, especially soldiers, who
are likely to be exposed to contaminated food or water, would also have a greater
risk of hepatitis A. Immunizing children with HAV vaccine as a routine schedule
should also be considered in Korea in the future, particularly if the disease
burden could be estimated and the cost-effectiveness of the vaccine could be
proved.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 10731917 [PubMed - indexed for MEDLINE]

780: Prog Lipid Res. 2000 Jan;39(1):3-18.

IRIV-adjuvanted hepatitis A vaccine: in vivo absorption and biophysical
characterization.

Zurbriggen R, Novak-Hofer I, Seelig A, Glück R.

Swiss Serum & Vaccine Institute, P.O. Box CH-3001, Berne, Switzerland.

Immunopotentiating reconstituted influenza virosomes (IRIV) are 150-nm
proteoliposomes composed of influenza surface glycoproteins and a mixture of
natural and synthetic phospholipids. Due to size, structure and composition of
the IRIVs, they serve as an antigen carrier system for efficacious vaccination,
as was demonstrated for hepatitis A and influenza. This paper reviews the unique 
properties of IRIVs and describes the in vivo biodistribution of model antigens
using 14C-labeled IRIVs and 125I-labeled streptavidin. IRIV formulated
streptavidin induced a strong depot effect after intra muscular (i.m.)
vaccination of mice, whereas soluble streptavidin was soon eliminated via the
kidney of the animals. A mixture of antigen and IRIVs yielded higher antibody
titers after i.m. inoculation than streptavidin alone. The highest
immunostimulation was achieved by the binding of the antigen to the investigated 
adjuvant. The potential penetration of inactivated hepatitis A virions into lipid
membranes was assessed by measuring the area increase of a lipid monolayer kept
at a constant surface pressure corresponding to that of lipid bilayer vesicles.
The monolayers were composed of phosphatidylcholine (POPC) and
phosphatidylethanolamine (POPE) (75/25 mol/mol), thus resembling the lipid
composition of the IRIV. The results suggested that the hepatitis A antigen may
spontaneously bind to the reconstituted IRIV membranes.

PMID: 10729605 [PubMed - indexed for MEDLINE]

781: Epidemiol Infect. 2000 Feb;124(1):121-30.

Hepatitis A in New South Wales, Australia from consumption of oysters: the first 
reported outbreak.

Conaty S, Bird P, Bell G, Kraa E, Grohmann G, McAnulty JM.

AIDS/Infectious Diseases Branch, NSW Health Department, North Sydney, Australia.

Between 22 January and 4 April 1997, 467 hepatitis A cases were reported to the
New South Wales Health Department, Australia. To identify the cause of the
outbreak, we conducted a matched case-control study, and an environmental
investigation. Among 66 cases and 66 postcode-matched controls, there was a
strong association between illness and consumption of oysters (adjusted odds
ratio 42; 95 % confidence interval 5-379). More than two-thirds of cases reported
eating oysters, including one third of cases and no controls who reported eating 
oysters in the Wallis Lake area. A public warning was issued on 14 February, and 
Wallis Lake oysters were withdrawn from sale. Hepatitis A virus was subsequently 
identified in oyster samples taken from the lake. Hepatitis A virus poses a
special risk to consumers who eat raw oysters because it can survive for long
periods in estuaries and cause severe disease.

PMID: 10722139 [PubMed - indexed for MEDLINE]

782: J Psychosom Res. 2000 Feb;48(2):107-13.

Patients' expressions of complaints as a predictor of the course of acute
hepatitis A.

Rose M, Scholler G, Jörres A, Danzer G, Klapp BF.

Department of Psychosomatic Medicine and Psychotherapy, Medical Clinic and
Policlinic, Charité, Campus Virchow, Humboldt University, Augustenburger Platz 1,
13353, Berlin, Germany. rose@charite.de

OBJECTIVE: Physical complaints, emotional states, liver, and immune parameters
were investigated as possible indicators of the course of hepatitis A. METHODS:
Forty-seven patients with hepatitis A were studied by means of the
Giessen-Complaint-Inventory (GBB) and the Berlin Mood Questionnaire (BSF), as
well as by taking into account their typical liver parameters and the following
immune parameters: alphaInterferon (alphaIFN), soluble Interleukin 2 receptor
(sIL-2R), Interleukin 6 (IL-6), Interleukin 1 receptor antagonist (IL-1Ra), and
Immunoglobulin M or G (IgM, IgG). Two hundred twenty-nine medical students and a 
representative German sample (n = 1557, Braehler et al.) served as controls.
RESULTS: We found that the initial degree of change in permeability of the liver 
cells, complaints about abdominal symptoms, and extent of depressive mood were
able to predict the length of hospital stay. Patients with the initial, more
pronounced liver damage, as well as patients who articulated less subjective
impairment proved to have a longer course of illness. Those patients who needed a
significantly longer time for recovery report, at admission, very few
complaints-fewer than even the normal population. We were not, however, able to
demonstrate a significant difference in the investigated immune parameters.
CONCLUSION: A certain denial tendency seems to be harmful with respect to the
recovery process and the immunological competence in the course of hepatitis A.

PMID: 10719126 [PubMed - indexed for MEDLINE]

783: J Child Neurol. 2000 Feb;15(2):135-6.

Fatality from hepatitis A in a child taking valproate.

Fayad M, Choueiri R, Mikati M.

Department of Pediatrics and Epilepsy Program, American University of Beirut
Medical Center, Lebanon. mrfayad@dm.net.lb

We report an 8-year-old boy with complex partial seizures due to congenital
stroke, treated with valproate for more than 3 years (the last 2 years were on
monotherapy) with no complications during that period except for transient
thrombocytopenia. His sister had uncomplicated hepatitis A. One month later, the 
patient became jaundiced, went into fulminant hepatic failure, and quickly became
encephalopathic despite discontinuation of valproate, aggressive supportive
therapy, and treatment with carmitine. He then died. He had positive hepatitis A 
IgM; other causes for acute hepatitis were ruled out. Liver pathology revealed
distended hepatocytes with cholestasis and microvesicular changes. We could find 
in the literature two other articles on four cases who developed liver failure
with hepatitis A while on valproate. All those cases, however, recovered. In our 
patient a usually benign disease became deadly, probably because of the
concomitant use of a hepatotoxic medication. Immunizing, with hepatitis A
vaccine, all children on valproate therapy who are living in, or traveling to,
endemic areas should be considered and is probably advisable.

Publication Types: 
    Case Reports

PMID: 10695901 [PubMed - indexed for MEDLINE]

784: Int J Infect Dis. 2000;4(1):34-7.

Prevalence of anti-hepatitis A antibodies in an urban middle class area of
Argentina: some associated factors.

López H, Zitto T, Baré P, Vidal G, Vukasovic J, Gómez R.

Center for Infectious Diseases, Buenos Aires, Argentina.

OBJECTIVE: This study evaluated the seroprevalence of hepatitis A virus (HAV)
antibodies in 360 middle-class subjects from Buenos Aires City and its outskirts.
METHODS: The study population included 360 individuals between 10 and 89 years of
age, from the socioeconomic middle class in Buenos Aires City and some suburban
areas of Buenos Aires province. Antibodies to hepatitis A virus were determined
by enzyme immunoassay test kits. RESULTS: The overall prevalence of HAV
antibodies was 42.2%. The highest percentage of seronegativity was found in the
subgroup of younger people without a history of symptomatic hepatitis and living 
in houses with more than one bathroom (86.9%). In the subgroup aged 21 to 60
years, the highest rates of seronegativity were found in individuals with higher 
level of education living in houses with tap water (66.6%). In both groups,
seronegativity may be correlated with a higher socioeconomic status. CONCLUSIONS:
In the middle-class community studied, more than 50% of people under 30 years of 
age were unprotected against HAV. Thus, the use of a vaccine against hepatitis A 
has to be considered for the prevention of symptomatic hepatitis, especially in
adults at risk of infection, such as those who travel to areas with poor
sanitation, taking into consideration that the severity of the disease increases 
with age.

PMID: 10689212 [PubMed - indexed for MEDLINE]

785: J Med Virol. 2000 Apr;60(4):363-6.

A large percentage of the Spanish population under 30 years of age is not
protected against hepatitis A.

Dal-Ré R, García-Corbeira P, García-de-Lomas J.

Medical Department, SmithKline Beecham Pharmaceuticals, Madrid, Spain.
rafael.dal-re@sb.com

A seroepidemiological study was conducted to assess the seroprevalence of
hepatitis A (HAV) antibodies in the Spanish general population in 1992-93. A
total of 2744 subjects (1337 men and 1437 women) in the 5-59 years age range were
stratified by gender and age (5-12, 13-19, 20-29, 30-39, 40-49, 50-59 years). The
presence of total anti-HAV antibodies was investigated using a commercial enzyme 
immunoassay. Fifty-five percent (95% CI: 53.5-57. 2%) of the subjects were
positive for anti-HAV antibodies, the age-standardized anti-HAV prevalence being 
65.4%. Prevalence of seropositive subjects increased with increasing age (chi(2) 
= 996, 17; P < 0.0001), being 11%, 25% and 54% for the 5-12, 13-19 and 20-29 age 
groups respectively. The results from this study showed a remarkable decline in
seroprevalence rates among children, adolescents and young adults. The large
number of susceptible subjects in these groups of the population has public
health implications in a country with intermediate HAV prevalence. Copyright 2000
Wiley-Liss, Inc.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 10686017 [PubMed - indexed for MEDLINE]

786: Vaccine. 2000 Feb 18;18 Suppl 1:S83-5.

Erratum in:
    Vaccine 2000 Aug 1;18(28):3326. Chicanna M [corrected to Chirona M].

From hepatitis B to hepatitis A and B prevention: the Puglia (Italy) experience.

Germinario C, Lopalco PL, Chirona M, Da Villa G.

Department of Internal Medicine, Institute of Hygiene, University of Bari, Piazza
Giulio Cesare 4, 1-70124, Bari, Italy.

The incidence of hepatitis B virus infection in Italy is 10 per 100, 000
population, with most cases occurring in young adults. Vaccination against
hepatitis B has been compulsory since 1991 for all newborns and 12-year-olds. In 
the Puglia region, this programme has reduced the incidence of hepatitis B from
7.4 per 100,000 population in 1990 to 2.4 per 100,000 population in 1996. The
number of notified cases of hepatitis B in Puglia decreased from 212 in 1992 to
73 in 1997. As 50% of these cases occurred in young adults, the main aim of the
current vaccination programme is to achieve high coverage rates among teenagers
and young adults within the next few years. Although the incidence of hepatitis A
is only about 5 per 100, 000 overall in Italy, Puglia is an area of intermediate 
endemicity with a seroprevalence of antibodies to hepatitis A virus (anti-HAV) of
about 40% in 18-year-olds. The incidence of hepatitis A is up to 30 per 100,000
between the periodic outbreaks that occur every 2-4 years. Most notified cases
occur in adolescents and young adults. The last outbreak of about 11,000 cases of
hepatitis A in the Puglia region occurred in 1996-1997, mainly in the summer
months in towns with harbours or near the coast. The most important risk factor
was initially consumption of raw seafood, but later was personal contact,
probably between children. A vaccination programme against hepatitis A was
initiated in Puglia in 1997, aiming to vaccinate all infants of 15-18 months and 
all 12-year-olds against hepatitis A. Infants receive monovalent hepatitis A
vaccine with the first dose of mumps/measles/rubella vaccine. Monovalent
hepatitis vaccine can be given with the second and third doses of hepatitis B
vaccine in 12-year-olds, but use of combined hepatitis A and B vaccine is
recommended to aid compliance and reduce the commitment of physician/nurse time. 
Vaccination can be performed in school.

PMID: 10683558 [PubMed - indexed for MEDLINE]

787: Vaccine. 2000 Feb 18;18 Suppl 1:S80-2.

Prospects for vaccination against hepatitis A and B in Catalonia (Spain).

Salleras L, Bruguera M, Buti M, Domíngez A.

Department of Health and Social Security, General Directorate of Public Health,
Travessera de les Corts, 131, Pavelló Ave María, 08028, Barcelona, Spain.

Catalonia is in an area of intermediate endemicity for hepatitis A virus (HAV)
infection. An Expert Committee has recently proposed the implementation of
universal hepatitis A vaccination for 12-year-olds, based on the fact that no
risk factors can be identified for hepatitis A in 50% of cases, and also that
selective vaccination targeted at high-risk groups has a limited potential to
reduce the incidence of hepatitis A. The well-established programme of hepatitis 
B vaccination of pre-adolescents in Catalonian schools has high levels of
vaccination coverage. This will provide a means to introduce hepatitis A
vaccination in a cost-effective way in schools, by replacing the single vaccine
with the combined hepatitis A and B vaccine. High-risk groups will also continue 
to be targeted. A pilot programme has commenced in the 1998/1999 school year and 
will be evaluated after 3 years. If it is successful, it will be extended
indefinitely.

PMID: 10683557 [PubMed - indexed for MEDLINE]

788: Vaccine. 2000 Feb 18;18 Suppl 1:S71-4.

Clinical course and consequences of hepatitis A infection.

Ciocca M.

Paediatric Hepatologist, Children's Hospital Juan P. Garrahan, Combate de los
Pozos 1881 (CP 1245), Capital Federal, Buenos Aires, Argentina.

Hepatitis A virus (HAV) is a small, non-enveloped RNA virus belonging to the
Picornaviridae, for which only one serotype has been identified. Transmission is 
usually through the faecal-oral route by person-to-person contact. The most
common risk factors are household or sexual contact with a sufferer, attendance
or working at a day-care centre, international travel, and association with food 
or waterborne outbreaks; 55% of cases have no identifiable risk factors. HAV
infection may be symptomatic or asymptomatic, and shows three phases. Virus is
shed during the incubation phase, anti-HAV IgM appears during the symptomatic
phase and can be used for diagnosis, and anti-HAV IgG appears at the same time
but persists lifelong. Unusual clinical manifestations of hepatitis A include
cholestatic, relapsing and fulminant hepatitis. Hepatitis A accounts for 93% of
cases of acute hepatitis in Argentina, including 7% of atypical clinical cases.
Hepatitis A is the major cause of fulminant hepatitis, and has been reported to
account for 10% of liver transplants in children in France and 20% in Argentina. 
One-year survival after liver transplantation is 64%. Prevention must be
considered as the main means of averting this severe illness.

PMID: 10683554 [PubMed - indexed for MEDLINE]

789: Vaccine. 2000 Feb 18;18 Suppl 1:S68-70.

Hepatitis A shifting epidemiology in Poland and Eastern Europe.

Cianciara J.

Institute of Infectious and Parasitic Diseases, Medical Academy of Warsaw, Wolska
37 str, 01-201, Warsaw, Poland.

The clinical morbidity of hepatitis A probably only represents 20% of cases of
hepatitis A virus (HAV) infection. When it became possible to determine specific 
antibodies, a seroepidemiological survey of anti-HAV was undertaken in Poland,
which showed that between 1979 and 1997 there was a shift in the peak age of
infection from childhood to adulthood, concomitant with a substantial decline in 
the incidence of HAV infection. Data from the World Health Organization also
indicate that there has also been a decline in the incidence of hepatitis A in
Eastern European countries in general, over the 3 years from 1994 to 1996. The
potential risk of epidemics still exists, however, when appropriate conditions
are created. The available data show that fewer young people are becoming
infected with HAV, and general preventive measures, including vaccination of
children and high-risk groups (e.g. healthcare and childcare personnel and those 
living in 'closed communities') are needed to deal with HAV infections in Eastern
Europe.

PMID: 10683553 [PubMed - indexed for MEDLINE]

790: Vaccine. 2000 Feb 18;18 Suppl 1:S65-7.

Hepatitis A shifting epidemiology in the Middle East and Africa.

Tufenkeji H.

Department of Paediatrics, King Faisal Specialist Hospital and Research Centre,
Riyadh, Saudi Arabia.

Data on the endemicity of hepatitis A virus (HAV) infection in Africa and the
Middle East are scant, but most of Africa appears to remain a high endemicity
region, with the exception of subpopulations in some areas, e.g. White people in 
South Africa. Saudi Arabia is a model for the Middle East, and is a country in
which shifting HAV epidemiology has been documented in recent years, concurrent
with the social and economic development that has occurred over the last two
decades. Earlier studies generally showed very high prevalence rates, with most
people becoming infected in early childhood. Between 1989 and 1995, however,
there was a significant fall in the seroprevalence of antibodies to HAV in
children up to 12 years old throughout the country except in one region bordering
the Yemen. The highest seroprevalence is found in children from rural
backgrounds, while the seroprevalences in Bedouin and urban children are similar.
Seroprevalence is related to socioeconomic status, being highest in the lowest
groups. Similar findings have been reported from other countries in the Middle
East. The existence of pockets of high endemicity for HAV infection with
surrounding areas shifting towards intermediate endemicity may lead to outbreaks,
and widespread vaccination should be considered.

PMID: 10683552 [PubMed - indexed for MEDLINE]

791: Vaccine. 2000 Feb 18;18 Suppl 1:S61-4.

Hepatitis A shifting epidemiology in South-East Asia and China.

Barzaga BN.

Department of Medical Microbiology, College of Public Health, University of the
Philippines, Manila, Philippines.

A review of the epidemiology of hepatitis A virus (HAV) infection over the last
20 years shows shifting patterns in the prevalence of antibodies to HAV
(anti-HAV) throughout South-East Asia and China. A number of countries have
shifted from high to moderate and from moderate to low endemicity, with a
corresponding increase in the age of exposure from childhood to early adulthood. 
The changes have resulted from improvements in hygiene, sanitation and the
quality of drinking water, reflecting improvements in living standards and
socioeconomic progress. In general in the late 1970s and early 1980s, 85-95% of
the population of developing countries like the Philippines, Korea, China and
Thailand were anti-HAV-positive by age 10-15 years, compared with only about 50% 
in the more affluent countries like Malaysia and Singapore. In the early 1990s,
85-95% of the population were immune by age 30-40 years in the Philippines,
Korea, China and Thailand, and by 50 years of age and above in Malaysia and
Singapore. Similar trends were noted in Hong Kong, Taiwan and Japan. Exposure to 
HAV at a later age may be associated with an increase in hepatitis A morbidity
and a greater propensity for outbreaks.

PMID: 10683551 [PubMed - indexed for MEDLINE]

792: Vaccine. 2000 Feb 18;18 Suppl 1:S57-60.

Hepatitis A shifting epidemiology in Latin America.

Tanaka J.

Biological Division, SmithKline Beecham Biologicals, Av. Insurgentes sur 1605 -
Piso 20, Col. San Jose Insurgentes, Delegacion Benito Juarez, Mexico City,
Mexico.

In the past, Latin America was considered to be an area of high endemicity for
hepatitis A virus (HAV) infection, with most people infected in early childhood. 
A seroepidemiological study was recently undertaken in six countries to determine
whether this pattern has changed. The highest seroprevalence of antibodies to HAV
(anti-HAV) was found in Mexico and the Dominican Republic. Analysis of the
different age groups showed that at age 6-10 years, 30% of children in Chile and 
54-55% in Brazil, Venezuela and Argentina had been infected, compared with almost
70% in Mexico and 80% in the Dominican Republic. At age 11-15 years, nearly 90%
in Mexico and 91% in the Dominican Republic had been infected, compared with 54% 
in Argentina, 62% in Venezuela, 60% in Brazil and 70% in Chile. By age 31-40
years, over 80% of the populations in all six countries had been exposed to HAV. 
In all of the countries except Brazil and Venezuela, the seroprevalence of
anti-HAV was significantly higher in females than in males. In Mexico, Argentina 
and Brazil, anti-HAV seroprevalence was significantly higher in the low
socioeconomic groups than in the middle/high socioeconomic groups. The results
show that there has been a shift from high to medium endemicity of HAV infection 
throughout Latin America, which may result in more clinical cases in adolescents 
and adults and a greater potential for outbreaks. The vaccination strategy for
hepatitis A should thus be reviewed.

PMID: 10683550 [PubMed - indexed for MEDLINE]

793: Med J Aust. 2000 Jan 3;172(1):19-21.

Comment in:
    Med J Aust. 2000 Jan 3;172(1):6-7.

Fulminant hepatitis A in indigenous children in north Queensland.

Hanna JN, Warnock TH, Shepherd RW, Selvey LA.

Queensland Health, Cairns. md1@health.qld.gov.au

Since 1993, three Indigenous children in north Queensland have died of fulminant 
hepatitis A. Even if the children had been able to undergo liver transplantation,
prolonged immunosuppressant therapy and the likelihood of opportunistic
infections would inevitably have jeopardised any chance of long-term survival. As
hepatitis A has become a leading infectious cause of death in young Indigenous
children in north Queensland, hepatitis A vaccine has recently been introduced
into the vaccination schedule for these children.

Publication Types: 
    Case Reports

PMID: 10682011 [PubMed - indexed for MEDLINE]

794: J Immunol Methods. 2000 Feb 3;234(1-2):23-34.

Use of linear and multiple antigenic peptides in the immunodiagnosis of acute
hepatitis A virus infection.

Gómara MJ, Riedemann S, Vega I, Ibarra H, Ercilla G, Haro I.

Departament de Química de Pèptids i Proteïnes, IIQAB-CSIC, Jordi Girona 18-26,
08034, Barcelona, Spain.

The reactivities of two panels of anti-HAV human sera from geographically
distinct areas (Chile and Spain) to synthetic peptides from the VP1, VP2 and VP3 
hepatitis A virus capsid proteins were examined by an enzyme-linked immunosorbent
assay (ELISA) procedure. Two and four branched multiple antigenic peptides (MAPs)
and palmitoylated peptides were compared with free synthetic sequences for the
detection of IgM anti-HAV antibodies in the two panels of human sera. Our results
showed that acute hepatitis A patient sera recognized preferentially homogeneous 
two branched MAPs and palmitic acid conjugated peptides. The palmitoyl-derived
VP3(110-121) peptide and the corresponding dimeric MAP were the most sensitive
and appropriate for serological studies of HAV-infected patients by ELISA,
sensitivity and specificity being higher than 90% and 95%, respectively. These
peptide-based tests open up new avenues in the development of peptide-based
immunosorbent assays for the detection of acute HAV disease.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 10669766 [PubMed - indexed for MEDLINE]

795: Hepatology. 2000 Feb;31(2):469-73.

The cost of hepatitis A infections in American adolescents and adults in 1997.

Berge JJ, Drennan DP, Jacobs RJ, Jakins A, Meyerhoff AS, Stubblefield W, Weinberg
M.

The incidence of hepatitis A has declined in the United States for several
decades, leading to an increased number of susceptible adolescents and adults.
Because clinical severity increases with age, hepatitis A infections in older
individuals cause greater morbidity, mortality, and treatment costs. Because the 
economic burden of hepatitis A has not been well described, we estimated its
costs, from the societal perspective, for patients infected at distinct ages. A
case-series study described treatment patterns, work loss, and symptom duration. 
Disease outcomes were estimated by an expert panel. Economic losses were
calculated by applying normative data reflecting treatment charges, employee
compensation, and the value of housekeeping services. In the case-series study,
mean treatment charges were $740 for nonhospitalized patients versus $6,914 for
hospitalized patients (P <.001). Symptom duration (67.8 vs. 34.4 days, P <.001)
and work loss (33.2 vs. 15.5 days, P <.01) were also greater for those
hospitalized. Nationally, we estimate 63,363 symptomatic hepatitis A infections
occurred among adolescents and adults during 1997, resulting in 8,403 hospital
admissions and 255 deaths. Nearly 2.5 million days of symptomatic illness and
829,000 work-loss days resulted, and 7,466 years of life were lost. Under
base-case assumptions, annual hepatitis A costs were estimated at $488.8 million.
In sensitivity analyses, this estimate varied from $332.4 to $579.9 million.
These costs may be reduced by regionally targeted vaccination of children, as
recommended by the Advisory Committee on Immunization Practices, although the
cost effectiveness of this policy has not yet been established.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 10655272 [PubMed - indexed for MEDLINE]

796: Pediatrics. 2000 Feb;105(2):436-8.

Liver failure attributable to hepatitis A virus infection in a developing
country.

Shah U, Habib Z, Kleinman RE.

In young children hepatitis A virus (HAV) infections are usually subclinical
events. However, HAV is also associated with progressive hepatic failure and even
death in some patients. This study was undertaken to characterize the course of
hepatitis A-related acute liver failure in children from a developing country
where hepatitis A is endemic and produces significant morbidity. Patients <15
years of age with confirmed hepatitis A, seen at the Aga Khan University Hospital
between January 1991 and August 1998 were identified using the patient registry. 
Of the 2735 patients seen with hepatitis A, 232 were admitted to the hospital. Of
these 30 patients developed progressive hepatic dysfunction and liver failure.
During this period, 45 children were admitted with liver failure attributable to 
other causes. Of the patients admitted with hepatitis A-related liver failure, 25
(83.3%) were encephalopathic at presentation and 36.7% of the patients died. The 
prothrombin time was the most significant predictor of survival. There was a
significant difference between those who survived and those who died on
discriminant analysis with respect to age, grade of hepatic encephalopathy,
duration of hospitalization, prothrombin time, and duration of jaundice when
taken as a group. There is a striking prevalence of liver dysfunction progressing
to hepatic failure among children seen at a hospital in Karachi, Pakistan. This
study demonstrates the significant morbidity and mortality that can attend HAV
infections in children in a developing country despite tertiary medical
facilities. The risk of HAV and its sequelae could probably be effectively
reduced in these settings with improved sanitation and universal immunization.

PMID: 10654972 [PubMed - indexed for MEDLINE]

797: J Occup Environ Med. 2000 Jan;42(1):83-7.

Evaluation of occupational transmission of hepatitis A virus among wastewater
workers.

Trout D, Mueller C, Venczel L, Krake A.

Division of Surveillance, Hazard Evaluation and Field Studies, National Institute
for Occupational Safety and Health, Cincinnati, Ohio 45226, USA.

To provide information concerning potential occupational transmission of
hepatitis A virus (HAV) among wastewater workers in a large city in the United
States, a cross-sectional survey was performed using a saliva test to detect
antibodies to HAV (anti-HAV). Fifty-nine (20%) of 302 participants tested
positive for anti-HAV. After controlling for the confounding effects of age and
race, wastewater work was not significantly associated with an increase in the
prevalence of anti-HAV (prevalence ratio = 1.3; 95% confidence interval 0.7 to
2.4). Additionally, when examining only the wastewater workers, no statistically 
significant occupational risk factors for anti-HAV were identified. The results
of this survey are consistent with the position of the Centers for Disease
Control and Prevention regarding groups at risk for HAV infection.

PMID: 10652693 [PubMed - indexed for MEDLINE]

798: Am J Gastroenterol. 2000 Jan;95(1):223-6.

Cost-effective analysis of hepatitis A prevention in Ireland.

Rajan E, Shattock AG, Fielding JF.

Mater Private Hospital, Dublin, Ireland.

OBJECTIVE: The purpose of this study was to determine the most cost-effective
prevention strategy against hepatitis A virus (HAV) infection for healthcare
workers and the general population at risk in Ireland. METHODS: Four prevention
strategies were compared: active immunization with Havrix Monodose (1440E.U);
screening for anti-HAV antibody and then vaccinating; passive immunization;
screening for anti-HAV antibody and then passive immunization. The cost-effective
ratio was calculated for each prevention strategy. Threshold analysis,
sensitivity analysis, and model extension to include indirect cost from work days
lost and secondary attack rates through horizontal transmission were also
derived. RESULTS: The medical costs were lowest and the infection rate highest
when no preventive action was taken. Vaccination was most cost effective when the
prevalence of immunity was 45% or less, reducing the infection rate by 98% when
compared to nonprevention. Screening before vaccination was most cost effective
when the prevalence of immunity was greater than 45%. Passive immunization and
screening before passive immunization were not comparable to the other strategies
in cost effectiveness. Sensitivity analysis showed that the cost-effective ratio 
for vaccination was dependent on vaccine price, incidence of HAV, and prevalence 
of immunity in the target group. Extending the model to include indirect costs
further increased the cost effectiveness of vaccination. CONCLUSION: The best
cost-effective strategy relates to target group immunity. Where HAV immunity is
45% or less, vaccination is the strategy of choice and when immunity is greater
than 45%, then screening followed by vaccination should be used. This study can
be used to provide a framework within which choices can be made to achieve better
health for less cost.

PMID: 10638588 [PubMed - indexed for MEDLINE]
