The changing epidemiology of hepatitis A in children and the consideration of active immunization in Korea

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.     

Epidemiology of hepatitis A in Finland in 1990–2007

The seroepidemiology of hepatitis A virus (HAV) for the period 1990–2007 and the molecular epidemiology for the period 1994–2007 in Finland were studied. The incidence of hepatitis A has been very low since 1990, at 0.3–3.6/100,000 inhabitants, excluding two outbreaks in 1994–1995 and 2002–2003, both of which were connected to intravenous drug use. Serum samples (3,217) collected in the period 1997–1998 were tested for hepatitis A antibodies to assess the percentage of seropositive Finns. More than 50% of Finns aged over 55 were seropositive for hepatitis A, while less than 5% of those aged under 40 were seropositive. In addition, patient samples (52,012) from the period 1990 to 2007 were assessed for antibodies against HAV. In these samples the proportion of acute HAV infections stayed at around 2% per year (excluding outbreaks), whereas the overall seropositivity for hepatitis A increased from some 30% to 45%, which was most likely due to increased vaccinations. For molecular epidemiology, samples from 1994 to 2007 were analyzed by RT‐PCR and sequencing. The results showed that most of the strains (82%) of HAV were of genotype IA but with an increasing number of genotypes IB and IIIA appearing during the last years of the study. All the cases seemed to be travel related and there was no endemic strain circulating in Finland. The low seroprevalence, especially in younger age groups, makes the population vulnerable to infection, which can be compensated for by increasing the number of vaccinations. J. Med. Virol. 82:934–941, 2010. © 2010 Wiley‐Liss, Inc.     

Anti-Hepatitis A Virus Immunoglobulin M Antibodies in Urine Samples for Rapid Diagnosis of Outbreaks

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°C but decreased when the samples were stored at 4°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.     

1963-2011年安溪县病毒性肝炎流行特征分析

目的探讨安溪县病毒性肝炎疫情的流行病学特征,为制定防制策略提供科学依据。方法采用描述性流行病学方法,分析疫情的流行和变化趋势。结果 1963-2011年共报告病毒性肝炎27155例,年均发病率为67.10/10万;死亡31例,年均死亡率为0.07/10万。流行具有周期性,近年来发病率呈上升趋势。男女性别比例为2.48：1;年龄以15～44岁为主,占64.13%;职业以农民为主,占50.63%。结论提高甲、乙肝疫苗的接种率是防制病毒性肝炎的关键,同时要注重丙、丁、戊型病毒性肝炎的防控。     

江门市2009-2011年感染性腹泻流行特征分析

目的了解江门市感染性腹泻的流行病学特征,分析监测系统中可能存在的问题。方法对江门市2009-2011年疾病监测信息报告系统中上报的感染性腹泻病例进行描述性流行病学分析。结果 2009-2011年江门市共报告感染性腹泻病例53624例,年发病率的范围为378/10万～428/10万,发病呈逐年上升趋势。5岁以下年龄组占全部发病数的40.64%。发病高峰在秋冬季节。报告发病率居前3位的市、区有鹤山、蓬江、新会等。3年共报告暴发疫情3起,全部为诺如病毒引起。结论感染性腹泻在江门市法定报告传染病中仍占有重要地位。今后应评估并完善感染性腹泻报告制度,加强监测与控制工作。     

Prevalence of antibodies against hepatitis A virus among children and adolescents in Germany

Since hepatitis A virus (HAV) infection during childhood is mostly asymptomatic, only seroprevalence studies can provide reliable information on incidence of HAV infection in children. The prevalence of anti-HAV antibodies was determined in sera taken in 2008 to 2010 from 1,645 children aged 0–17 years and in sera taken in 2010–2011 from 400 adult blood donors in Germany. For examination of trend over time, 715 sera collected between 1999 and 2006 from children at the age of 0–17 years within the federal state Thuringia were included. Antibody testing was carried out using the test kits ETI-AB-HAVK PLUS and ETI-HA-IGMK PLUS from DiaSorin. In children, the overall prevalence of antibodies was 10.8 %. After the seroprevalence declined from 8.8 % among the 0–2 year-olds to 2.4 % among the 3–4 year-olds, there was a significant increase to 20.5 % in the group of the 15–17 year-olds. Boys had with 12.7 % a significantly higher seroprevalence of anti-HAV antibodies compared to 8.8 % among girls. In adult blood donors, there was a HAV seroprevalence of 19.3 %. The likelihood of past infection or immunization within the age groups of children from 0 to 12 years differed significantly from that of adults. In conclusion, in Germany, only a small number of HAV infections occur in children, especially up to the age of 12 years. The proportion of susceptible children is greater than the proportion of susceptible adults. Thus, during outbreaks, the rate of infection among children would usually be higher than the rate among adults.     

Epidemiological and clinical features of norovirus gastroenteritis in outbreaks: a population-based study

Noroviruses are the most frequent cause of acute gastroenteritis in the community. In Catalonia, it is not clear how this type of viral gastroenteritis is evolving, and the objective of this prospective population-based study was to describe the incidence and epidemiological and clinical features of outbreaks of acute gastroenteritis due to norovirus in Catalonia between October 2004 and October 2005. Incidence rates were calculated using the estimated population of Catalonia in 2005. For each outbreak, the mode of transmission, the number of persons affected, demographic variables, clinical presentation, the date and time of onset of symptoms and the duration of symptoms, physician visits and hospitalizations were collected. Sixty viral outbreaks affecting 1791 people were identified, with no distinct seasonality. The mean number of outbreaks per month was 4.6. The global incidence was 24.6 per 100 000 person-years. The incidence was higher in women (25.7 per 100 000 person-years) and in the 5–11 years (52.4 per 100 000 person-years) and ≥65 years (42.4 per 100 000 person-years) age groups. The prevalence of vomiting, abdominal pain and general malaise was higher in children and adolescents, whereas the prevalence of diarrhoea and myalgia was higher in adults. These results suggest that norovirus infection has an important public health impact in Catalonia and that prevention strategies should be designed and implemented.     

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

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.     

Multiplex polymerase chain reaction test for the diagnosis of acute viral hepatitis A

Background/Aims

The early diagnosis of acute hepatitis A (AHA) is hindered because serum IgM against hepatitis A virus (HAV) can yield false-negative results during the window period. This study evaluated the diagnostic accuracy of a polymerase chain reaction (PCR) kit for HAV RNA for the diagnosis of AHA.

Methods

Samples were collected from 136 patients with acute severe hepatitis at their admission to Asan Medical Center between June 2010 and July 2010. Samples were analyzed for serum IgM anti-HAV using an immunoassay test and for qualitative HAV RNA using the Magicplex HepaTrio PCR test kit. The diagnostic accuracies of these methods were tested on the basis of clinical and laboratory diagnoses of AHA.

Results

The concordance rate and kappa value between IgM anti-HAV and HAV RNA PCR were 88.2% and 0.707, respectively. For the diagnosis of AHA, the sensitivity and specificity of IgM anti-HAV were 90.7% and 100%, respectively, when an "equivocal" result was regarded as positive; and 79.1% and 100%, respectively, when an "equivocal" result was regarded as negative. The sensitivity and specificity of HAV RNA PCR were 81.4% and 100%, respectively. All four patients with negative IgM anti-HAV and positive HAV RNA PCR results and all four patients with equivocal IgM anti-HAV RNA and positive HAV RNA PCR results were eventually diagnosed with AHA.

Conclusions

The qualitative HAV RNA PCR test has an equivalent diagnostic accuracy for AHA compared to IgM anti-HAV and may be more sensitive during the window period.     

Detection of hepatitis A virus genotype IB variants in clams from Maputo Bay, Mozambique

Clams provide an important source of food and income for the population of Maputo, Mozambique, where conditions of poor water supply and inadequate sanitation favor endemic infection with hepatitis A virus (HAV). To determine the role of bivalves in an endemic area, clams gathered from Maputo Bay were bought from market and examined for HAV. Four batches, total 150 clams, were sampled over the year. RNA extracted from individual digestive glands was assayed by nested RT-PCR and sequencing of HAV 5' noncoding region (5' NCR). Specific HAV signals were detected in one batch, 23 of 34 clams (67%) testing positive. Phylogenetic analyses of VP3/VP1, VP1/P2A, and 5' NCR determined clustering of clam strains as genotype I, subtype B. In addition to identifying HAV IB strains with predicted conserved amino acid sequence, IB variants exhibiting novel amino acid substitutions at the VP1/P2A junction were detected. HAV strains from clams showed 93%-99% homology with wild-type IB strains from South African outbreaks and from a panel of HAV IgM positive Swedish patients. DNA from enteric human adenovirus 40/41 was found in a limited number of clams from two batches, 6/34 (17%) and 4/35 (11%). Detection of HAV subgenotype IB in bivalves provided indirect evidence of the strains circulating in a densely populated coastal region where HAV is presumed to be hyperendemic. The results suggest that clams may be an important source of HAV in Maputo region, and indicate the need for further molecular study of strains circulating in the indigenous population.     

Analysis of genetic and serology of hepatitis A virus infection during and after outbreak in two junior high schools in Surabaya,Indonesia

Outbreaks of hepatitis A have occurred in some cities in Indonesia. In Surabaya, the capital city of East Java province, Indonesia, hepatitis A outbreaks have been reported since2013, with a marked increase in the number of cases in 2015. The aim of the present study was to analyze the genetic and serology of acute symptomatic cases (early infection) during a hepatitis A outbreak and asymptomatic cases after the outbreak in two junior high schools in Surabaya in 2015 to 2016. Students with acute symptomatic hepatitis A during the outbreak and other students who were asymptomatic 3 to 4 months after the outbreak were enrolled. Asymptomatic students had no symptoms from the outbreak until they were enrolled. Sera were collected to identify anti-hepatitis A virus (HAV) IgM (by enzyme-linked immunosorbent assay) and HAV genetic variations/genotypes (using polymerase chain reaction [PCR]-sequencing and phylogenetic analysis). A total of 33 (97.1%) out of 34 sera of students with acute symptoms were positive for anti-HAV IgM and 18% of them were positive by PCR, identified as HAV subgenotype IA. No prominent amino acid variations were observed from reported HAV sequences from Indonesia. Among 38 sera of asymptomatic students, most (55.3%) were positive for anti-HAV IgM, while none were positive by PCR. In conclusion, HAV-IA was the only subgenotype identified in acute symptomatic cases during the outbreak. The percentage of HAV-specific IgM-positive cases was very high among acute symptomatic students, but that was also high among asymptomatic students, which might contribute as the important source of infection during the outbreak.     

梅州市2003—2007年乙类传染病疫情动态分析

目的探讨梅州市乙类传染病发生、流行与变动趋势，为传染病预防控制提供科学依据。方法采用描述流行病学方法分析梅州市2003—2007年乙类传染病流行及发病趋势。结果2003—2007年全市共报告乙类传染病16种42821例，年均发病率为187．45／10万；死亡病种6种163例，年均死亡率为0．71／10万。呼吸道传染病占发病总数的58．65％，年均发病率109．94／10万，居各类传染病发病第1位；血源及性传播传染病占发病总数的36．56％，年均发病率68．54／10万，居各类传染病发病第2位。年均发病率居前2位的是肺结核、病毒性肝炎。狂犬病是死亡人数最多的传染病，占死亡总数的63．80％。HIV感染率呈逐年上升趋势。结论今后梅州市传染病防治重点是加强肺结核、病毒性肝炎、狂犬病和HIV／AIDS等预防控制工作。     

The immune structure and specific laboratory indices of acute hepatitis A in lower monkeys of the Sukhumi Nursery

The study of the rate of occurrence of hepatitis A (HA) markers among monkeys, both newly arriving and those born and living for long periods (aboriginals) in the Sukhumi farm, was carried out. The rate of detection of antibody to HAV (anti-HAV) was shown to vary from 47% (Papio hamadryas) to 100% (Macaca arctoides and Macaca fascicularis). The level of infection with HAV varied among different groups of the same species: Macaca rhesus from 30% to 96%, Papio hamadryas from 0 to 82%. During a long-term observation period seroconversion to HAV was observed in monkeys arriving to the farm from natural habitats. In M. rhesus upon arrival the anti-HAV were detected in 7% and by the end of the observation period reached 100%, in green monkeys 28% and 92%, respectively. Anti-HAV of the IgM class were detected in animals with seroconversion. In fecal extracts from M. rhesus and in the liver, feces, and intestinal contents of green monkeys HAV was found cross-reacting with simian and human sera containing anti-HAV. The virions isolated from a green monkey liver had a buoyant density in CsCl 1.36 g/cm3, and HAV from feces of a M. rhesus sedimented in the density zone of 1.34 g/cm3.     

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.     

Determinants of Hepatitis A Vaccine Immunity in a Cohort of Human Immunodeficiency Virus-Infected Children Living in Switzerland

Vaccination in HIV-infected children is often less effective than in healthy children. The goal of this study was to assess vaccine responses to hepatitis A virus (HAV) in HIV-infected children. Children of the Swiss Mother and Child HIV Cohort Study (MoCHiV) were enrolled prospectively. Recommendations for initial, catch-up, and additional HAV immunizations were based upon baseline antibody concentrations and vaccine history. HAV IgG was assessed by enzyme-linked immunosorbent assay (ELISA) with a protective cutoff value defined as ≥10 mIU/ml. Eighty-seven patients were included (median age, 11 years; range, 3.4 to 21.2 years). Forty-two patients were seropositive (48.3%) for HAV. Among 45 (51.7%) seronegative patients, 36 had not received any HAV vaccine dose and were considered naïve. Vaccine responses were assessed after the first dose in 29/35 naïve patients and after the second dose in 33/39 children (25 initially naïve patients, 4 seronegative patients, and 4 seropositive patients that had already received 1 dose of vaccine). Seroconversion was 86% after 1 dose and 97% after 2 doses, with a geometric mean concentration of 962 mIU/ml after the second dose. A baseline CD4⁺ T cell count below 750 cells/μl significantly reduced the post-2nd-dose response (P = 0.005). Despite a high rate of seroconversion, patients with CD4⁺ T cell counts of <750/μl had lower anti-HAV antibody concentrations. This may translate into a shorter protection time. Hence, monitoring humoral immunity may be necessary to provide supplementary doses as needed.     

Hepatitis A antibody titres after infection and immunization: implications for passive and active immunization

Titres of antibodies against hepatitis A virus (HAV) were determined in patients, in donors, and in volunteers after active, passive, and combined immunization. Highest titres were found in recently infected persons: in 109 IgM anti-HAV positive persons, the geometric mean titre (GMT) was 15,400 mlU/ml. The GMT in 265 anti-HAV positive blood donors was 10,700 mlU/ml. The anti-HAV seroprevalence in 19,746 donors increases with age: at the age of 40 years, 50% have antibodies. Titres after active, passive, and combined immunization were studied in three groups: 51 persons received inactivated HAV vaccine at months 0, 1, and 6. The GMT after the booster was 3,400 mlU/ml at month 7. All persons produced more than 100 mlU/ml anti-HAV. Forty-nine persons received both 5 ml immunoglobulin and three vaccinations, yielding a GMT of 1,300 mlU/ml at month 7. One person in this group produced less than 100 mlU/ml anti-HAV. Forty-nine persons received 5 ml immunoglobulin intramuscularly. At day 5 the GMT was 96 mlU/ml. The estimated minimum protective level (10 mlU/ml) was reached in 3 months. Hepatitis A vaccination may supersede the use of immunoglobulin as prophylaxis for travellers to endemic areas. Passive immunization remains necessary for protection during outbreaks. The dosage regimen for passive immunization is based on old studies using preparations with unknown anti-HAV content. Concern regarding the antibody levels in immunoglobulin preparations is justified; the prevalence of HAV antibodies in developed countries continues to fall. Our results indicate that dosage regimens should be reconsidered. Dosage should be deduced logically from the anti-HAV antibody content of the immunoglobulin preparation. © 1993 Wiley-Liss, Inc.     

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

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.