Changing seroepidemiology of hepatitis A virus infection in Taiwan

Hepatitis A antibody (anti-HAV) in serum was studied from June to October, 1984, by radioimmunoassay in 647 male and 553 female apparently healthy children under 15 years of age in Taipei City. The prevalence rate of anti-HAV was 27.0% in infants, decreased to around 1% during the preschool age, then increased and remained around 5% until 11-12 years of age, when another increase was noted, and reached 13.6% among the early teenagers. The age-specific prevalence of anti-HAV increased with age but differed in three age ranges, which reflected three apparently different calculated annual incidences. Compared with previous studies in Taipei, the results showed a significant reduction in the prevalence of anti-HAV in almost every age group from 3 to 14 years. This fact probably reflects the marked improvement of hygienic conditions and progress in health education in recent years, which reduced the exposure to HAV infection among young children. The age of primary infection in the children was older than in previous studies, and it is expected that the susceptibility of HAV will extend to early adulthood.     

Molecular epidemiology of hepatitis E virus in Hong Kong

Hepatitis E virus (HEV) is one of the major causes of acute and self‐limiting hepatitis in human. In Hong Kong, the number of notifications increased from 26 to 62 from year 2001 to 2007. This study describes the molecular epidemiology of HEV in Hong Kong in order to determine the movement and distribution of HEV. HEV in 171 serum samples from HEV IgM positive cases from year 2001 to 2007 were amplified using RT‐PCR and subjected to nucleotide sequencing. Phylogenetic analysis showed 162 of 171 HEV detected cases (94.7%) belonged to genotype IV and 8 (4.7%) to genotype I. Interestingly, a cluster of 10 cases in year 2007 that had the same sequence of HEV was identified. Epidemiological data however did not detect any relationship between these cases. Since zoonotic transmission is a well known route of HEV infection, close monitoring of the circulating HEV strains in human and food source animals may help to provide additional information on the transmission of HEV and possible source of infection in Hong Kong. J. Med. Virol. 81:1062–1068, 2009. © 2009 Wiley‐Liss, Inc.     

Incidence of hepatitis A virus (HAV) infection in rural Liberia

To provide background for future hepatitis A vaccine trials, sera were collected from 0- to 4-year-old Liberian infants and their mothers on two occasions an average of 14.75 months apart and tested for antibody to hepatitis A virus (anti-HAV). The prevalence of anti-HAV rose from 2.5% in infants 0-6 months of age to 70% in children 3-4 years of age and did not differ between male and female infants. The annual incidence of new infections was slightly lower in the first year of life (35%) than in the subsequent 3 years, when it averaged 45%. The presence of HBV infection did not affect the incidence of HAV seroconversion. No clinical hepatitis was recognized in the subjects who seroconverted. Dual hepatitis A and B virus infection were observed; these were all clinically inapparent. The extraordinary incidence of HAV infection documented in the present study offers an opportunity for vaccine efficacy trials requiring minimal numbers of subjects.     

Prevalence of hepatitis A antibodies in schoolchildren in Catalonia (Spain) after the introduction of universal hepatitis A immunization

The objective of this study was to investigate the prevalence of hepatitis A antibodies (anti-HAV) in schoolchildren in Catalonia and to compare it with the rates found in previous studies. Sera from a representative sample of 1,342 children aged between 6 and 15 years, recruited in 2001, were tested for anti-HAV. The results were related to sociodemographic variables and vaccination history. The overall prevalence of anti-HAV was 51.4%. The prevalence was 5.5% in non-vaccinated children, similar to that found in a 1996 study, and 96.6% in vaccinated children. The prevalence of anti-HAV in non-vaccinated children increased significantly with age, reaching 11.6% in the 13-15 years age group. The prevalence of anti-HAV was higher in children born outside Catalonia than in those born in Catalonia (16.1% vs. 5.0%, P = 0.02). The expected continuation in the decline in the prevalence of anti-HAV in non-vaccinated schoolchildren, observed in Catalonia since 1986, was not found in 2001. The rate of anti-HAV in 2001 was slightly higher than in 1996, although the difference was not statistically significant (5.5 and 3.5%, respectively). This could be explained by the increased number of recent immigrant children born outside Catalonia, mainly in countries where hepatitis A is highly endemic.     

Change in hepatitis A virus seroepidemiology in southern Taiwan: a large percentage of the population lack protective antibody

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.     

Seroprevalence of hepatitis E virus in Hong Kong, 2008–2009

The public health impact of hepatitis E virus (HEV) infection varies across the world. An HEV vaccine has been recently approved for clinical use in China. Population‐specific seroprevalence data are essential for cost‐effective assessment of vaccination programs. Here, a cross‐sectional study was performed to provide an update on the local seroprevalence of HEV. An archive of serum samples submitted for virological investigation between 2008 and 2009 to a general hospital was used. A total of 450 samples with equal numbers from each gender covering the age groups from 1–10 to >80 years (25 samples per group) were tested for HEV immunoglobulin G (IgG) by enzyme‐linked immunoassay. Age‐ and gender‐specific seroprevalence were determined. The HEV IgG positive rate increased from 8% among 1–10 years to 56% among >80 years. The increase in prevalence was constant throughout all age groups without a steeper slope or plateau observed from any age group. The overall positive rate among males was significantly higher than among females (32.9% vs. 24.4%, P = 0.048). The best‐fitted seroprevalence curves also suggested a higher positive rate for males across all age groups. Increased HEV IgG positivity was noted in comparison with historical local studies. Collectively, the prevalence of HEV in Hong Kong has increased over the past decade. A large proportion of the population is still susceptible to infection, and all age groups are at risk. Territory‐wide vaccination program should be considered. J. Med. Virol. 85:459–461, 2013. © 2012 Wiley Periodicals, Inc.     

Lack of complement-dependent cytolytic antibodies in hepatitis A virus infection

Sera collected from patients with acute hepatitis A virus (HAV) infection and convalescent sera were examined for cytolytic activity against HAV-infected human-embryo lung fibroblasts (HAV carrier fibroblasts). Using the 51chromium release assay, no complement dependent antibody mediated cytolytic activity against HAV carrier cells could be detected. In control experiments with identical cell strains, anti-herpes simplex virus (HSV) positive sera and complement caused specific lysis of HSV type 1 infected target cells. The data presented here do not support the hypothesis that in the possible immunopathogenesis of HAV infection, complement-dependent cytolytic antibodies play an essential role.     

Optimal time for repeating the IgM anti-hepatitis A virus antibody test in acute hepatitis A patients with a negative initial test

Background/Aims

The nonspecific clinical presentation of acute hepatitis A (AHA) mandates the detection of anti-hepatitis A virus IgM antibodies (IgM anti-HAV) in the serum for obtaining a definitive diagnosis. However, IgM anti-HAV might not be present during the early phase of the disease. The aim of this study was to determine the optimal time for repeating the IgM anti-HAV test (HAV test) in AHA patients with a negative initial test.

Methods

In total, 261 patients hospitalized with AHA were enrolled for this retrospective study. AHA was diagnosed when the test for IgM anti-HAV was positive and the serum alanine aminotransferase (ALT) level was ≥400 IU/L. Repeat HAV test was conducted after 1-2 weeks if the initial HAV test was negative but AHA was still clinically suspected.

Results

The results of the initial HAV test were negative in 28 (10.7%) patients. The intervals from symptom onset to the initial-HAV-test day and from the peak-ALT day to the initial-HAV-test day were significantly shorter in the negative-initial-HAV-test group, but on multivariate analysis only the latter was significantly associated with negative results for the initial HAV test (β=-0.978; odds ratio [95% confidence interval]=0.376 [0.189-0.747]; P=0.005). The HAV test was positive in all patients when it was performed at least 2 days after the peak-ALT day.

Conclusions

The results of HAV tests were significantly associated with the interval from the peak-ALT day to the HAV-test day. The optimal time for repeating the HAV test in clinically suspicious AHA patients with a negative initial HAV test appears to be at least 2 days after the peak-ALT day.     

Antibody persistence and immune memory in healthy adults following vaccination with a two-dose inactivated hepatitis A vaccine: long-term follow-up at 15 years

Long‐term persistence of vaccine‐induced immune response in adults was assessed annually for 15 years following primary immunization with a two‐dose inactivated hepatitis A vaccine. In 1992, 119 and 194 subjects aged 17–40 years and naïve for hepatitis A virus (HAV) were enrolled in two studies to receive 1,440 ELISA units (El.U) of inactivated hepatitis A vaccine (Havrix?, GlaxoSmithKline Biologicals, Belgium) according to a standard 0, 6 or an extended 0, 12 months schedule, respectively. Serum samples were taken 1 month after the second vaccine dose and every consecutive year up to 15 years after primary vaccination for measurement of anti‐HAV antibody concentrations (NCT00291876 and NCT00289757). At year 15, 100% (48/48) and 97.3% (108/111) of subjects vaccinated at 0, 6 or 0, 12 months remained seropositive for anti‐HAV antibodies, with geometric mean concentrations (GMCs) of 289.2 and 367.4 mIU/ml, respectively. An additional dose of HAV vaccine (1,440 El.U) was administered to the six subjects who had become seronegative for anti‐HAV antibodies since year 11. All subjects mounted a humoral immune response to the additional HAV challenge dose, although post‐challenge anti‐HAV antibody levels remained low in one subject. These studies represent the longest annual follow‐up of hepatitis A vaccine in healthy adults. The immune response induced by two doses of this inactivated HAV vaccine was shown to persist for at least 15 years. No difference in long‐term antibody persistence was observed between the two primary vaccination schedules, reinforcing the potential for flexibility in the timing of the second primary vaccine dose. J. Med. Virol. 83:1885–1891, 2011. © 2011 Wiley‐Liss, Inc.     

Transmission of hepatitis A virus among recently captured Panamanian owl monkeys

The presence of antibody to hepatitis A virus (anti-HAV) in 60% of procured owl monkeys (Aotus trivirgatus) held within the United States prompted a study of recently captured A trivirgatus in Panama. Only 2 of 145 newly captured monkeys, but all of 35 A trivirgatus held within a colony for over 100 days, were found to have anti-HAV. Of 41 sero-negative, newly captured monkeys followed prospectively, 25 became infected with hepatitis A virus (HAV) as evidenced by seroconversion or demonstration of virus in the liver at death. Only one monkey that survived over 60 days within the colony was not infected. HAV was identified in the feces of most infected monkeys prior to the development of antibody and was antigenically indistinguishable from human HAV in cross-blocking radioimmunoassays. This colony-centered epizootic provides strong evidence that A trivirgatus is susceptible to HAV and should be investigated further as a potential model of human hepatitis A.     

Changing seroepidemiology of hepatitis B, C, and D virus infections in high-risk populations

Needle-sharing and sexual contact are important transmission routes of hepatitis B, C, and D virus (HBV, HCV, HDV) infection. This study aimed to investigate the current status of these viral infections among high-risk populations including prostitutes and intravenous (i.v.) drug users, compared with the prevalence rate reported previously to examine the changing seroepidemiology. Of the 916 female prostitutes, 79 (9%) were positive for antibody to HCV (anti-HCV), 111 (12%) were positive for HBV surface antigen (HBsAg), and 5 (5%) had antibody to HDV (anti-HDV). The prevalence rate was significantly lower compared to that in 1989-1991 (12%, P = 0.037) for HCV infection, and to that in 1988 (59%) and 1996 (40%) (P < 0.0001) for HDV infection. Of the 494 i.v. drug users, 87 (18%) patients were HBsAg carriers and 12 (14%) were anti-HDV-positive. The prevalence rate of HDV infection was significantly lower than that reported in 1985 (79%, P < 0.0001). Among the 443 tested i.v. drug users, 182 (41%) were anti-HCV-positive, significantly lower than that in 1985 (53%, P = 0.026). Of the 263 male prostitutes, 11 (4%) were anti-HCV-positive, 45 (17%) were HBsAg-positive, and 7 (16%) were anti-HDV-positive. Of the 129 illegal immigrant prostitutes, 7 (5%) were anti-HCV-positive, 15 (12%) were HBsAg-positive and none were positive for anti-HDV. In conclusion, the findings indicate a declining prevalence of HCV and HDV infections among drug users and prostitutes over the past 16 years. Male prostitutes and immigrant prostitutes are new "high-risk" populations and may become a reservoir for disease transmission.     

Antibodies to Hepatitis A Virus in Immune Serum Globulin

Two hundred one immune serum globulin (ISG) lots manufactured in the US between 1967 and 1977 were tested for antibodies to the hepatitis A virus (anti-HAV) by a competitive-inhibition radioimmunoassay (RIA); a lesser number were also tested by immune adherence hemagglutination (IAHA). The percentage of ISG lots that contained anti-HAV with a titer of 1:100 or greater by RIA was 50% for those manufactured in 1967, 69% for those manufactured in 1972, and 100% for those manufactured in 1977. The percentage of lots with anti-HAV titers equal to or greater than 1:500 by RIA was 7% in 1967, 18% in 1972, and 70% in 1977. Only ten lots of ISG (5%) had anti-HAV titers of 1:1,000 or greater by RIA; seven of these were manufactured in 1977. Both the mean titer of anti-HAV in ISG lots and the percentage of lots containing significant titers of this antibody appear to have increased in the US over the past ten years. This may reflect the increased use of source plasma from paid plasmapheresis donors in the US during this period. The lower titers of anti-HAV in the older lots of ISG studied were shown not to be due to fragmentation of antibody molecules during storage.     

Seroepidemiological investigation of patients and family contacts in an epidemic of hepatitis A.

Serial blood and faecal samples were collected from patients and family contacts during an outbreak of hepatitis A in a village and tested by a solid-phase competitive type radioimmunoassay for hepatitis A antigen and hepatitis A antibody. The amount and duration of excretion of hepatitis A antigen was correlated with the severity of the illness. In 2 severe clinical cases, hepatitis A antigen was demonstrated in faecal extracts 11 days before the onset of jaundice and continuing for 10 days thereafter, with maximum shedding during the late incubation period. Faecal antigen was demonstrated in low concentrations for only 2 days in a patient with mild disease and in a person with subclinical infection. There was an inverse correlation between the incidence of infection and prevalence of hepatitis A antibody and age. Of 24 infections, 19 (79%) occurred in persons in the age group 0 to 20 years, a group in which only 6% of individuals had pre-existing antibody. Hepatitis A antibody was present in the serum of 3 persons in low titres of 1:20 to 1:40 on the day jaundice developed. The antibody titres increased very rapidly during the following 2 weeks of illness and slowly during the following months, reaching titres of 1:900 to 1:3500. In a separate study, a mean antibody titre of 1:591 was found in 13 patients, 12 years after clinical hepatitis A with jaundice.     

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

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.     

Drift in the hypervariable region of the hepatitis C virus during 27 years in two patients

Serial serum samples were obtained over a 27-year period from a hepatitis C virus (HCV)-infected patient and from a nurse who appeared to become infected by this patient. The hypervariable region 1 (HVR1) and 5'noncoding region (5'NCR) of the HCV genome were amplified from each serum sample by polymerase chain reaction (PCR) and cloned. In the first serum specimen from the patient and the first two serum specimens from the nurse, most of the 20 clones from each serum sample had one common sequence in the HVR1 gene. All later serum samples contained a heterogeneous mixture of HCV quasispecies. The uniformity of the HVR1 sequence in the early samples and the emergence of greater diversity in later serum samples is consistent with the apparent transmission of HCV between the patient and nurse and the eventual emergence of other quasispecies as the virus replicated in the new host. In addition, the immune globulin given to the nurse may have been responsible for some of the HCV quasispecies changes observed in her serum.     

Prevalence of hepatitis A virus,hepatitis B virus,hepatitis C virus,hepatitis D virus and hepatitis E virus as causes of acute viral hepatitis in North India: A hospital based study

Context: Acute viral hepatitis (AVH) is a major public health problem and is an important cause of morbidity and mortality. Aim: The aim of the present study is to determine the prevalence of hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis D virus (HDV) and hepatitis E virus (HEV) as causes of AVH in a tertiary care hospital of North India. Settings and Design: Blood samples and clinical information was collected from cases of AVH referred to the Grade I viral diagnostic laboratory over a 1-year period. Subjects and Methods: Samples were tested for hepatitis B surface antigen, anti-HCV total antibodies, anti-HAV immunoglobulin M (IgM) and anti-HEV IgM by the enzyme-linked immunosorbent assay. PCR for nucleic acid detection of HBV and HCV was also carried out. Those positive for HBV infection were tested for anti-HDV antibodies. Statistical Analysis Used: Fisher’s exact test was used and a P < 0.05 was considered to be statistically significant. Results: Of the 267 viral hepatitis cases, 62 (23.22%) patients presented as acute hepatic failure. HAV (26.96%) was identified as the most common cause of acute hepatitis followed by HEV (17.97%), HBV (16.10%) and HCV (11.98%). Co-infections with more than one virus were present in 34 cases; HAV-HEV co-infection being the most common. HEV was the most important cause of acute hepatic failure followed by co-infection with HAV and HEV. An indication towards epidemiological shift of HAV infection from children to adults with a rise in HAV prevalence was seen. Conclusions: To the best of our knowledge, this is the first report indicating epidemiological shift of HAV in Uttar Pradesh.     

Recent trends in hepatitis A incidence in Brazil

Hepatitis A incidence has been decreasing in Brazil since child vaccination was implemented in 2014. This trend was interrupted by an outbreak among adult male in São Paulo in 2017. This study was outlined to estimate whether the increase of hepatitis A cases among adult men in Brazil was restricted to São Paulo. Cases reported to the national surveillance system from 14 large cities of all Brazilian regions were analyzed. Trends in time series from 2012 to 2018 were estimated by Prais-Winsten regression. The outbreak in São Paulo extended to 2018. In Rio de Janeiro, the number of cases rose again, achieving the same levels reported before the vaccination era. Three of six cities from South and Southeast regions showed an upward trend in the number of cases among adult men (P < .005). The large cities in the other three Brazilian macroregions showed a decrease or stabilization of cases without an increase among male adults. The increase of hepatitis A virus (HAV) cases in Brazil has happened not only in São Paulo, but also in other cities of South and Southeast regions. The northernmost cities were not affected. A change in the epidemiological pattern of HAV infection is emerging in Southern Brazil.     

Secular trend and geographical variation in hepatitis A infection and hepatitis B carrier rate among adolescents in Taiwan: An island-wide survey

Improved standards of sanitation have contributed to a shift in the prevalence of hepatitis A in countries such as Greece. Children are now coming into first contact with the infection at an increasingly later age, leaving more adults susceptible to the disease. In military forces where close living conditions prevail, the likelihood of infection is even more pronounced. An inactivated hepatitis A vaccine has been developed and has been administered successfully to over 24,000 healthy children and adults. This vaccine would be of considerable benefit to military personnel worldwide. The reactogenicity and immunogenicity of a hepatitis A vaccine were evaluated in 200 female military recruits, aged from 17 to 23 years, vaccinated according to a primary vaccination schedule at 0 and 1 months with a booster dose at 6 months. Symptoms reported following vaccination were generally mild and transient. Soreness at the site of injection was the most frequent local symptom and malaise was the most common general symptom. Clinically significant increases in serum liver enzyme levels were not detected. All subjects had seroconverted after the primary vaccination course and maintained anti-HAV titres up to the time of the administration of the booster dose. The booster dose produced more than a tenfold increase in the geometric mean titre (GMT). © 1993 Wiley-Liss, Inc.