Declining prevalence of hepatitis A virus antibodies among children from low socioeconomic groups reinforces the need for the implementation of hepatitis A vaccination in Brazil

Age-related seroprevalence studies that have been conducted in Brazil have indicated a transition from a high to a medium endemicity of hepatitis A virus (HAV) infection in the population. However, most of these studies have focused on urban populations that experience lower incidence rates of HAV infection. In the current study, the prevalence of anti-HAV antibodies was investigated in children with a low socioeconomic status (SES) that live on the periphery of three capital cities in Brazil. A total of 1,162 dried blood spot samples were collected from individuals whose ages ranged from one-18 years and tested for anti-HAV antibodies. A large number of children under five years old (74.1-90%) were identified to be susceptible to HAV infection. The anti-HAV antibody prevalence reached ≥ 50% among those that were 10-14 years of age or older. The anti-HAV prevalence rates observed were characteristics of regions with intermediate level of hepatitis A endemicity. These data indicated that a large proportion of children with a low SES that live at the periphery of urban cities might be at risk of contracting an HAV infection. The hepatitis A vaccine that is currently offered in Brazil is only available for high-risk groups or at private clinics and is unaffordable for individuals with a lower SES. The results from this study suggest that the hepatitis A vaccine should be included in the Brazilian National Program for Immunisation.     

Antibodies to the hepatitis A virus in the healthy population of Moscow

Serum specimens collected from 1002 persons in Moscow were tested for the presence of antibodies to hepatitis A virus (anti-HAV antibodies) by solid-phase enzyme immunoassay. The prevalence of these antibodies increased progressively with age from 10% in children aged 5-9 years to over 90% in the age groups of 40-49 years and over, the 50% immunity level being established at the age of 18 years. 79% of infants under 1 year were found to be immune, which was obviously due to the placental transfer of antibodies from mother to child. In a considerable part of seropositive persons over 30 years high or medium antibody titers were detected. These age groups showed a stable proportion of the low, medium and high level of anti-HAV antibodies. The prevalence of such antibodies was not related to sex. The presence of an ample amount of anti-HAV antibodies was determined in all of 18 tested lots of commercial serum immunoglobulin obtained from 3 different manufacturers.     

Serum antibodies to the hepatitis A virus in persons following a history of the infection

Enzyme immunoassay was used for titration of serum antibodies in subjects with a history of clinically pronounced or asymptomatic hepatitis A infection. Titers of hepatitis A virus antibodies (anti-HAV) essentially decreased during 3-4 years after the disease, then the rate of this decrease slowed down and antibody titers stabilized at low levels. After clinically pronounced hepatitis A anti-HAV levels were considerably higher than after the asymptomatic form of this infection.     

Distribution of anti-HAV in a population sample from Puglia

To investigate the prevalence and distribution of antibody to hepatitis A virus (anti-HAV), we tested by solid phase radioimmunoassay method 461 sera of selected people of Bari, according to age. In addiction, sera from cord blood of 11 newborns and their mothers at delivery were also investigated for anti-HAV. Taken together 64.4 per cent of subjects tested were found to be anti-HAV positive. The rate of antibody detection was strongly correlated with age. The prevalence were 4.5 per cent from 6 months to 3 years but gradually increased throughout childhood (from 35.6 to 80 per cent). Anti-HAV was detected in all cord blood samples from newborns whose mothers carried anti-HAV. These data suggest that circulation of hepatitis A virus in our area is very high, so that serological evidence of infection become evident in the majority of individuals during infancy.     

Immunoenzyme determination of IgA specific anti-HAV in the serological diagnosis of hepatitis A

A capture enzyme immuno assay for the detection in the serum of specific IgA antibodies to HAV is described. A total of 203 sera from patients and controls were tested. IgA anti-HAV were present only in sera from patients with recent hepatitis A. 23 patients were followed prospectively and IgA anti-HAV were at detectable levels for at least six months after the onset. The detection of IgA anti-HAV is proposed as an important test to differentiate hepatitis A with persistent hypertransaminasemia from non-A, non-B patients.     

Antibodies against HBV, HCV and HAV detected by using microparticle enzyme immunoassay in hepatitis outpatients

The presence of the hepatitis B surface antigen (HBsAg), of the antibodies against HBc, HCV and HAV was determined in outpatients in the period September 2005 - December 2006. The serum samples were analyzed by using Enzyme Immunoassay microparticles (Abbott AxSYM System). At least one test was positive in 238 patients (15.4%) of the total of 1547 patients. Of the 238 positive subjects, in 130 positive subjects (54.6%) the existence of HBV infection could be ascertained based on the presence of HBsAg or of the antibodies against HBc or of their association; 83 patients (34.9%) presented antibodies against HCV and in other 12 patients the antibodies against HCV were associated with HBsAg or with antibodies against HBc, suggesting the coexistence of HCV and HBV infection. The antibodies against HCV and the associations between HCV and HBV were mostly detected in subjects with the diagnosis of cirrhosis, liver failure or chronic hepatitis. Of the 13 (5.46%) patients with antibodies against HAV, 6 patients presented the associations: in 2 cases antibodies anti-HAV with positive HBsAg, in 1 case antibodies anti-HAV and anti-HBc with positive HBsAg, in 2 cases antibodies anti-HAV and anti-HBc and in 1 case antibodies anti-HAV and anti-HCV.     

Prevalence of antibodies to hepatitis A virus in Nova Scotia children.

Blood samples from 304 children aged 6 months to 16 years were tested by radioimmunoassay for antibodies to hepatitis A virus (anti-HAV). Of several factors examined for a possible association with the prevalence of anti-HAV--age, sex, race, geographic location and presence of malignant disease--only age showed a positive correlation with the prevalence of these antibodies.     

Shifting seroepidemiology of hepatitis A in Japan, 1973-2003

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.     

Prevalence of antibody to hepatitis A virus in a Canadian Inuit community.

To determine the prevalence of hepatitis A in a Canadian Inuit population, serum from 85% of the 850 inhabitants of Baker Lake, Northwest Territories, was tested by radioimmunoassay for antibody to the hepatitis A virus (anti-HAV). The overall prevalence of anti-HAV in the community was 71%. Exposure to the virus occurred early in life, such that by the age of 6 years 53% of the children had anti-HAV in their serum. The rate approached 100% by the age of 50 years. These findings document the ubiquitous nature of the hepatitis A virus in this northern Inuit settlement and suggest that immunoprophylaxis be considered for individuals taking short-term employment in such places.     

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

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.     

Longitudinal Study of Hepatitis A Infection by Saliva Sampling: The Kinetics of HAV Markers in Saliva Revealed the Application of Saliva Tests for Hepatitis A Study

Despite the increasing numbers of studies investigating hepatitis A diagnostic through saliva, the frequency and the pattern of hepatitis A virus (HAV) markers in this fluid still remains unknown. To address this issue, we carried on a longitudinal study to examine the kinetics of HAV markers in saliva, in comparison with serum samples. The present study followed-up ten patients with acute hepatitis A infection during 180 days post diagnosis (dpd). Total anti-HAV was detected in paired serum and saliva samples until the end of the follow-up, showing a peak titer at 90^th. However, total anti-HAV level was higher in serum than in saliva samples. This HAV marker showed a probability of 100% to be detected in both serum and saliva during 180 dpd. The IgM anti-HAV could be detected in saliva up to 150 dpd, showing the highest frequency at 30^th, when it was detected in all individuals. During the first month of HAV infection, this acute HAV marker showed a detection probability of 100% in paired samples. The detection of IgM anti-HAV in saliva was not dependent on its level in serum, HAV-RNA detection and/or viral load, since no association was found between IgM anti-HAV positivity in saliva and any of these parameter (p>0.05). Most of the patients (80%) were found to contain HAV-RNA in saliva, mainly at early acute phase (30^th day). However, it was possible to demonstrate the HAV RNA presence in paired samples for more than 90 days, even after seroconversion. No significant relationship was observed between salivary HAV-RNA positivity and serum viral load, demonstrating that serum viral load is not predictive of HAV-RNA detection in saliva. Similar viral load was seen in paired samples (on average 10⁴ copies/mL). These data demonstrate that the best diagnostic coverage can be achieved by salivary anti-HAV antibodies and HAV-RNA tests during 30–90 dpd. The long detection and high probability of specific-HAV antibodies positivity in saliva samples make the assessment of salivary antibodies a useful tool for diagnosis and epidemiological studies. The high frequency of HAV-RNA in saliva and the probability of detection of about 50%, during the first 30 dpd, demonstrate that saliva is also useful for molecular investigation of hepatitis A cases, mainly during the early course of infection. Therefore, the collection of saliva may provide a simple, cheap and non-invasive means of diagnosis, epidemiological surveys and monitoring of hepatitis A infection purposes.     

The chronic course of spontaneous and experimental hepatitis A in rhesus monkeys with viral persistence]

The prolonged (up to 2 years) complex observation of 11 rhesus macaques (Macaca mulatta) with spontaneous hepatitis A and 14 rhesus macaques with experimental hepatitis A developing after their intravenous and/or oral infection with human hepatitis A virus (HAV). Both natural and experimental infection took a chronic course (15-18 months). In 13 monkeys showing morphological changes in the liver during the whole period of the disease elevated enzyme levels in the blood and virus shedding in feces were periodically observed. Only one monkey had acute hepatitis A which lasted 1.5 months. In 11 monkeys the disease took an undulating course with 1-2 relapses when virological, biochemical and morphological signs of the disease could be detected. Seroconversion was observed in all monkeys. Anti-HAV IgM antibodies were retained for not more than 6-7 months and total anti-HAV antibodies, during the whole period of observation. Relapses were found to induce no antibody formation. Evidence on the prolonged (up to 12-16 months) persistence of HAV in primates was obtained for the first time.     

Detection of hepatitis A, B, and C virus-specific antibodies using oral fluid for epidemiological studies

In this report, we examine the adaptability of commercially available serological kits to detect antibodies markers for viral hepatitis in oral fluid samples. We also assessed the prevalence of hepatitis A, B, and C virus-specific antibodies, and related risk factors for these infectious diseases through sensitivity of the tests in saliva samples to evaluate if oralfluid can be an alternative tool to substitute serum in diagnosis of acute viral hepatitis and in epidemiological studies. One hundred and ten paired serum and saliva specimens from suspect patients of having acute hepatitis were collected to detect antibodies to hepatitis A (total and IgM), hepatitis B (anti-HBs, total anti-HBc and IgM anti-HBc), and hepatitis C (anti-HCV) using commercially available enzyme-linked immunossorbent assay (EIA). In relation to serum samples, oral fluid assay sensitivity and specificity were as follows: 87 and 100% for total anti-HAV, 79 and 100% for anti-HAVIgM, 6 and 95% for anti-HBs, 13 and 100%for total anti-HBc, 100 and 100% for anti-HBc IgM, and 75 and 100% for anti-HCV The consistency observed between antibodies tests in saliva and expected risk factors for hepatitis A and C suggests that the saliva method could replace serum in epidemiological studies for hepatitis A and C.     

The results of a controlled field trial of a dried erythrocytic immunoglobulin diagnostic agent for detecting the hepatitis A virus antigen]

The results of the controlled field trial of lyophilized erythrocytic immunoglobulin diagnosticum for the detection of hepatitis A virus antigen in the urine and feces of patients are presented. This diagnosticum was used for the study of urine and fecal samples from 225 patients (of these, 176 had hepatitis A) and 54 healthy persons in the passive hemagglutination (PHA) test. Their blood sera were studied in the PHA test (to detect HBsAg) and the radioimmunoassay (to detect anti-HAV IgM). The immunoglobulin diagnosticum under study was found to be nonspecific and faintly sensitive and, therefore, unsuitable for use in medical practice.     

Seroepidemiology of hepatitis A virus infection in Japan: An area of very low endemicity

The incidence of hepatitis A virus (HAV) infection has declined significantly worldwide, including in Japan. A nationwide seroepidemiological study on hepatitis A in Japan has taken place almost every 10 years since 1973, and the last study was performed in 2003. In the present study, we describe the latest seroepidemiological pattern of hepatitis A in Japan using 7867 serum specimens obtained from healthy individuals collected between 2013 and 2017, approximately 10 years after the last study. Among them, 223 were anti-HAV positive. About 68% of individuals aged 60 years and older had anti-HAV antibodies, whereas only 1.1% of those aged below 60 years old had immunity; thus, almost all individuals younger than 60 years of age were HAV susceptible. In comparison with previous investigations, the susceptible population has increased and aged. According to data from the National Epidemiological Surveillance of Infectious Diseases (NESID) program, between 1989 and 2016, the proportion of patients with hepatitis A aged 60 years and older continuously increased with each year. The NESID data also suggested that recently, typical large foodborne outbreaks of hepatitis A have become rare, and cases tend to be reported among at-risk groups; overseas travelers contributed to 25% of hepatitis A cases, and in 2018, the first nationwide hepatitis A outbreak that affected mostly men who have sex with men was reported. The purpose of this study was to determine the current status of HAV infection in Japan, based on both seroepidemiology and the national surveillance data from the NESID.     

Studies on transmission of hepatitis A virus to squirrel monkeys

Non-human primates have been playing an essential role in the study of hepatitis A virus (HAV) biology, pathogenesis and for testing candidate HAV vaccines. This study was to determine the suitability of squirrel monkeys (Saimiri sciureus) as animal model for HAV infection. Animals were inoculated, either intragastrically or intravenously, with a Brazilian HAV isolate (HAF-203). Alanine aminotransferase (ALT) and anti-HAV antibodies (IgM and total) were monitored. Feces were daily collected for HAV antigen and HAV RNA detection. Samples of liver tissue were obtained by biopsy before inoculation at peak ALT levels and/or when anti-HAV antibodies developed, and at necropsy for morphological examination. Monkeys inoculated by the intravenous route rapidly developed significant elevations of serum ALT, anti-HAV antibodies, and liver histologic changes, while the only evidence of HAV infection in intragastrically inoculated animals was the seroconversion. Moreover, squirrel monkeys excreted very low levels of HAV detectable in only few fecal samples after amplification by RT-PCR, different from humans and other non-human primate species that eliminate large quantities of virus during the late incubation period. The unusual onset of hepatitis A in experimentally infected squirrel monkeys represent an important obstacle for its use as animal model for the study of this viral infection. However, they can represent a valuable tool for the obtention of hyperimmune sera for HAV, in the view of the very high titer of anti-HAV developed (10⁵) 24 days after a single intravenous inoculation.     

Hepatitis E virus infection in selected Brazilian populations

A retrospective study on the prevalence of hepatitis E virus (HEV) infection was conducted in selected populations in Rio de Janeiro, Brazil. A total of 1,115 subjects were tested including 146 patients with acute Non-A Non-B Non-C (NANBNC) viral hepatitis, 65 hemodialysis patients, 93 blood donors, 102 intravenous drug users (IVDUs), 304 pregnant women, 145 individuals living in the rural area and 260 individuals living in the urban area. In order to characterize a favorable epidemiological set for enterically transmitted infection in the studied populations we also evaluated the prevalence of anti-HAV IgG (hepatitis A virus) antibodies. Specific antibodies to HEV (anti-HEV IgG) were detected by a commercial EIA and specific antibodies to HAV (anti-HAV IgG) were detected using a competitive "in house" EIA. We found a high prevalence of anti-HAV IgG in these populations, that could indicate some risk for infections transmitted via the fecal-oral route. The anti-HEV IgG prevalence among the different groups were: 2.1% in patients with acute NANBNC viral hepatitis, 6.2% in hemodialysis patients, 4.3% in blood donors, 11.8% in IVDUs, 1% in pregnant women, and 2.1% in individuals form the rural area. Among individuals living in the urban area we did not find a single positive serum sample. Our results demonstrated the presence of anti-HEV IgG in almost all studied populations; however, further studies are necessary to establish the real situation of HEV epidemiology in Rio de Janeiro, Brazil.