Cynomolgus monkeys (Macaca fascicularis) experimentally infected with B19V and hepatitis A virus: no evidence of the co-infection as a cause of acute liver failure

This study was conducted to analyse the course and the outcome of the liver disease in the co-infected animals in order to evaluate a possible synergic effect of human parvovirus B19 (B19V) and hepatitis A virus (HAV) co-infection. Nine adult cynomolgus monkeys were inoculated with serum obtained from a fatal case of B19V infection and/or a faecal suspension of acute HAV. The presence of specific antibodies to HAV and B19V, liver enzyme levels, viraemia, haematological changes, and necroinflammatory liver lesions were used for monitoring the infections. Seroconversion was confirmed in all infected groups. A similar pattern of B19V infection to human disease was observed, which was characterised by high and persistent viraemia in association with reticulocytopenia and mild to moderate anaemia during the period of investigation (59 days). Additionally, the intranuclear inclusion bodies were observed in pro-erythroblast cell from an infected cynomolgus and B19V Ag in hepatocytes. The erythroid hypoplasia and decrease in lymphocyte counts were more evident in the co-infected group. The present results demonstrated, for the first time, the susceptibility of cynomolgus to B19V infection, but it did not show a worsening of liver histopathology in the co-infected group.

Reappraisal of the Immunogenicity and Safety of Three Hepatitis A Vaccines in Adolescents

Although the overall incidence of hepatitis A in Korea has been decreasing, adolescents remain highly vulnerable to its outbreaks. This study was conducted to compare the immunogenicity and safety of three hepatitis A vaccines in Korean adolescents. Healthy anti-hepatitis A virus seronegative subjects aged 13 to 19 yr were randomized in three equal groups to receive two doses of Avaxim(TM), Epaxal(R), or Havrix(R), 6 to 12 months apart. Seroconversion rates one month after the first dose were 98%, 95%, and 93% for Avaxim(TM), Epaxal(R), and Havrix(R), respectively. Seroconversion rates reached 100% for all vaccine groups one month after the second dose. Anti-HAV geometric mean concentrations (GMCs) were 7,207.7 mIU/mL (95% CI, 6023.1-8684.7), 1,750.5 mIU/mL (95% CI, 1362.9-2248.3), and 1,953.5 mIU/mL (95% CI, 1459.4-2614.7) after two doses of Avaxim(TM), Epaxal(R), and Havrix(R) respectively. Avaxim(TM) was significantly more immunogenic than Epaxal(R) and Havrix(R), whereas there were no significant differences in antibody responses between Epaxal(R) and Havrix(R). Local and systemic solicited adverse events (AEs) were mostly of mild-to-moderate intensity and resolved within 5 days. No serious AEs were reported. In conclusion, all three vaccines are highly immunogenic and well-tolerated in Korean adolescents. (Clinical Trial Registry NCT00483470)

Using immunoglobulin Y as an alternative antibody for the detection of hepatitis A virus in frozen liver sections

An increasing amount of research has been conducted on immunoglobulin Y (IgY) because the use of IgY offers several advantages with respect to diagnostic testing, including its easy accessibility, low cost and translatability to large-scale production, in addition to the fact that it can be ethically produced. In a previous work, immunoglobulin was produced and purified from egg yolks (IgY) reactive to hepatitis A virus (HAV) antigens. In the present work, this anti-HAV-specific IgY was used in an indirect immunofluorescence assay to detect viral antigens in liver biopsies that were obtained from experimentally infected cynomolgus monkeys. Fields that were positive for HAV antigen were detected in liver sections using confocal microscopy. In conclusion, egg yolks from immunised hens may be a reliable source for antibody production, which can be employed for immunological studies.

The Immunogenicity of a Single Dose of Hepatitis A Virus Vaccines (Havrix(R) and Epaxal(R)) in Korean Young Adults

PURPOSE: Assessing the immunogenicity of a single dose of hepatitis A virus (HAV) vaccines is important because some people receive only a single dose. However, previous studies have shown variable results and have not examined the effects of demographic characteristics other than gender. This study was performed to examine the immunogenicity of a single dose of HAV vaccine according to the vaccine type and demographic characteristics in young adults. MATERIALS AND METHODS: Seronegative medical school students were randomly allocated to receive either Havrix or Epaxal. RESULTS: After approximately 11 months, the seroconversion rate in 451 participants was 80.7%. In men, the Havrix group showed a significantly higher seroconversion rate (81.9%) than the Epaxal group (69.2%), whereas both vaccine groups showed similarly high immunogenicity in women (Havrix: 90.1%, Epaxal: 92.9%; P for interaction=0.062). According to the results of a multivariate analysis, Epaxal showed significantly lower immunogenicity than Havrix only in men. Age, obesity, drinking, smoking, and follow-up time did not significantly affect seroconversion in either gender. CONCLUSION: The seroconversion rate of single-dose HAV vaccines was low in men, particularly in those who received Epaxal. Our results suggest that gender effects should be considered when comparing the immunogenicity of different HAV vaccines.

Epidemiological and serological aspects of hepatitis A among children and teenagers in the city of Santos: a cross-sectional study / Aspectos epidemiológicos e sorológicos da hepatite A em crianças e adolescentes na cidade de Santos: estudo transversal

CONTEXT AND OBJECTIVE: Viral hepatitis A is still a concern at public health level in Brazil and around the world, due both to the number of affected subjects and the possibility of complications in the acute forms. The Brazilian Ministry of Health estimates that at least 70% of this country's population has already had contact with the hepatitis A virus (HAV). The aim here was to discover the prevalence of serological markers for the hepatitis A virus among children and teenagers at daycare facilities, kindergartens and elementary schools in the city of Santos. DESIGN AND SETTING: Cross-sectional study in kindergartens and elementary schools within the municipal education network in several regions of the city of Santos. METHOD: Students' family members were surveyed using a questionnaire and 4,680 finger-prick blood samples were taken and assayed by means of the ELISA technique. RESULTS: The general prevalence of anti-HAV IgG was 9.72% and, of these cases, 74.6% were reactive to anti-HAV IgM. There was higher prevalence of anti-HAV IgG among older children, females, children who played in streams, those whose homes were not connected to the sewage system, those whose parents had low education levels, those with low household income and those who did not live along the seashore. The prevalence of anti-HAV IgM peaked in the early years and subsequently fell, and it was lower on the hills and in the Northwestern Zone. CONCLUSION: The general prevalence of serological markers for hepatitis A was low in Santos.

CONTEXTO E OBJETIVO: A hepatite viral A continua sendo uma preocupação em nível de saúde pública no Brasil e no mundo, tanto pelo número de indivíduos atingidos, como pela possibilidade de complicação das formas agudas. O Ministério da Saúde estima que pelo menos 70% da população do Brasil já tiveram contato com o vírus da hepatite A. O objetivo foi conhecer a prevalência de marcadores sorológicos do vírus da hepatite A em crianças e adolescentes de creches e escolas de ensino infantil e fundamental na cidade de Santos. TIPO DE ESTUDO E LOCAL: Estudo transversal em pré-escolas e de ensino fundamental da rede municipal em diversas regiões da cidade de Santos. MÉTODO: Foi aplicado um questionário aos familiares dos estudantes e coletadas 4.680 amostras de sangue através de punção capilar para realização da sorologia pela técnica ELISA. RESULTADOS: A prevalência geral do anti-HVA IgG foi de 9,72% e, desses, 74,6% foram anti-HVA IgM reagentes. A prevalência de anti-HVA IgG foi maior entre as crianças mais velhas, meninas, aquelas que brincavam em córregos, sem rede de coleta de esgoto em sua moradia, de pais com baixa instrução, de baixa renda familiar e aquelas que não eram moradoras da orla. A prevalência de anti-HVA IgM teve pico nos primeiros anos e posterior queda e, no morro e Zona Noroeste, foi mais baixa. CONCLUSÃO: A prevalência geral dos marcadores sorológicos para hepatite A foi baixa em Santos.

Seroprevalence of hepatitis A immunity among brazilian adult patients with liver cirrhosis: is HAV vaccination necessary?

BACKGROUND: Patients with chronic liver disease have a higher risk of fulminant hepatitis when infected with hepatitis A virus, and vaccination of these patients against such infection is recommended. In Brazil, mainly in the South and Southeast regions, the epidemiology of hepatitis A (HA) has shifted from high to intermediate endemicity, which would have implication on policy of HA vaccination for these populations. OBJECTIVE: To verify the prevalence of HA immunity in adult patients with liver cirrhosis (LC), in Uberlândia MG, a city of Southeastern Brazil. METHODS: Between December 2005 and December 2006, 106 patients with LC were consecutively evaluated. In addition, 75 individuals without LC or alcoholism were evaluated (control group - CG). RESULTS: Total anti-HAV (ELISA methods) was positive in 104 (98.1 percent) patients with LC (82 men, 24 women; mean age, 53.3 ± 11.9 years) and in 74 (98.7 percent) individuals of the CG (55 men, 20 women; mean age, 47 ± 11.6 years), p > 0.05. CONCLUSIONS: For patients with chronic liver disease, in the geographic regions and age groups evaluated, routine vaccination against hepatitis A is not recommended. Moreover, the serum determination of total anti-HAV, used to assess immunity, is five times cheaper than vaccination against hepatitis A and, for this reason, should precede vaccination.

Mudança na suscetibilidade à hepatite A em crianças e adolescentes na última década / Shifting susceptibility to hepatitis A among children and adolescents over the past decade

OBJETIVOS: Estimar a prevalência de anticorpos contra hepatite A (anti-VHA) em grupo de crianças e adolescentes de laboratório público e privado em Porto Alegre e comparar com estudo realizado na década anterior. MÉTODOS: Entre 2007 e 2008 foi realizado estudo transversal onde foram incluídas, consecutivamente, 465 amostras de soros de crianças e adolescentes entre 1 e 19 anos de idade para determinar a prevalência de anticorpos anti-VHA total. As amostras foram fornecidas por laboratório público (grupo 1), que atende somente Sistema Único de Saúde, e por laboratório privado (grupo 2), representando os estratos socioeconômicos mais baixo e mais alto, respectivamente. O teste foi realizado em único laboratório (eletroquimioluminescência, Roche Diagnostics). Resultados > 20 UI/L foram considerados positivos. RESULTADOS: A soroprevalência de anti-VHA no grupo 1 foi de 37,6 por cento e o percentual de positividade aumentou conforme a idade, variando de 19,4 por cento entre 1-4 anos a 54,1 por cento entre 15-19 anos. No grupo 2, a frequência de anti-VHA foi de 46,1 por cento e foi inversamente relacionada à idade, caindo de cerca de 50,0 por cento nas faixas etárias menores para 29,1 por cento aos 15-19 anos. Houve diminuição significativa na prevalência do anti-VHA nas crianças de 5-9 anos do grupo 1 (p = 0,03), quando comparadas com estudo realizado na década de 1990. CONCLUSÕES: Os resultados sugerem queda na endemicidade da hepatite A em Porto Alegre na última década e indicam maior suscetibilidade à doença em crianças e adolescentes, principalmente no estrato socioeconômico mais baixo.

OBJECTIVES: To estimate the prevalence of anti-hepatitis A virus (anti-HAV) antibodies in serum samples from children and adolescents obtained at two clinical pathology laboratories in the city of Porto Alegre, south of Brazil, and to compare findings to those of a study carried out in the 1990s. METHODS: In this cross-sectional study conducted between 2007 and 2008, 465 serum samples obtained from subjects aged 1-19 years were consecutively tested to determine the prevalence of total anti-HAV antibodies. Samples were provided by a public laboratory (group 1) that serves the Unified Health System exclusively, meant to represent the lowest socioeconomic strata, and by a private laboratory (group 2), meant to represent the higher socioeconomic classes. Tests were performed at a single laboratory using commercially available electrochemiluminescence kits. Antibody levels > 20 UI/L were considered positive. RESULTS: The seroprevalence of anti-HAV in Group 1 was 37.6 percent. The percentage of anti-HAV reactivity increased from 19.4 percent in the 1-to-4 group to 54.1 percent in the 15-to-19 group. In Group 2, overall anti-HAV positivity was 46.1 percent and was inversely correlated with age, declining from roughly 50 percent in the youngest groups to 29.1 percent in the 15-to-19 group. Comparison of sample findings to those reported in a 1990s study showed a significant reduction in anti-HAV prevalence among 5-to-9-year-olds in group 1 (p = 0.03). CONCLUSIONS: The results suggest that the endemicity of hepatitis A in Porto Alegre has been declining over the past decade, and that children and adolescents, particularly those in the lowest socioeconomic strata, are more susceptible to the disease.

Vaccination with a Human Papillomavirus (HPV)-16/18 AS04-Adjuvanted Cervical Cancer Vaccine in Korean Girls Aged 10-14 Years

The human papillomavirus (HPV)-16/18 AS04-adjuvanted cervical cancer vaccine has been demonstrated to be highly efficacious and immunogenic with a favorable safety profile. This study assessed the immunogenicity and safety of the HPV-16/18 AS04-adjuvanted vaccine in healthy Korean girls aged 10-14 yr. This multi-center, observer-blind trial randomly assigned 321 healthy girls to receive three doses (0, 1, 6-month schedule) of HPV-16/18 AS04-adjuvanted vaccine or hepatitis A vaccine. Immunogenicity against vaccine antigens was assessed one month post-Dose 3. Solicited and unsolicited adverse events (AEs) and serious AEs (SAEs) were recorded. In the according-to-protocol analysis, all initially seronegative subjects vaccinated with the HPV-16/18 AS04-adjuvanted vaccine had seroconverted at Month 7, with a peak geometric mean titer (GMT) that was 600-fold higher than the natural infection titer of 29.8 EU/mL for HPV-16 and a peak GMT that was 400-fold higher than the natural infection titer of 22.6 EU/mL for HPV-18. The vaccine was well tolerated with no increase in reactogenicity with subsequent doses and no reports of vaccine-related SAEs. In conclusion, the HPV-16/18 AS04-adjuvanted vaccine is shown to be highly immunogenic and generally well-tolerated in Korean girls aged 10-14 yr.

Profile of viral hepatitis A in Chennai.

This retrospective study compares the clinical features, laboratory profile and complications of anti HAV IgM positive acute viral hepatitis A in 138 children between 1-15 year (1-5 year: n=31; 5-10 year: n=85; and 10-15year: n=22). We found that older children presented with HAV (hepatitis A virus) infection with more atypical manifestations (ascites and splenomegaly) and complications.

Current Status and Vaccine Indication for Hepatitis A Virus Infection in Korea / 대한소화기학회지

One of the major cause of recent acute viral hepatitis in Korean adults is hepatitis A virus (HAV) infection. Most of hepatitis A cases are young adults in their twenties or thirties, and the severity of the disease is related to the age of patients. The seroprevalence of HAV among the adolescents and young adults in their teens and twenties is about 10%, which suggests that a growing number of young adults are susceptible to HAV infection. Development of more adult cases with severe presentation is expected in the near future, and some preliminary data suggest the incidence rate of hepatitis A in Korea might be higher than 20/100,000 population. This clinical features and the epidemiological shift of HAV urge to promote childhood vaccination and consider catch-up vaccination for adolescents and young adults. More extensive evaluation on the nationwide epidemiology of HAV infection, cost-benefit analysis of HAV vaccination, and setting-up of guidelines for HAV vaccination are urgently warranted.

Cambios en la epidemiología de las hepatitis virales en Chile y consideraciones en estrategias de prevención / The changing epidemiology of viral hepatitis in Chile

The social and sanitary changes that Chile is experiencing will change the epidemiologic profile of viral hepatitis. Virus A hepatitis will displace to older ages, and immunization plans with specific vaccines should be considered. The real prevalence of hepatitis B may be higher, due to an underreporting of the disease. The education and vaccination of high risk groups should be reinforced. E virus hepatitis requires more research in risk groups and in certain animal species consumed by humans. C virus hepatitis is the greatest challenge as it causes chronic liver disease and is the main cause for liver transplantation.

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

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

Prevenção das hepatites virais através de imunização / Viral hepatitis prevention by immunization

OBJETIVO: Apresentar uma revisão atualizada e crítica da prevenção das hepatites virais A e B, através de imunização. FONTE DOS DADOS: Revisão de artigos médicos obtidos através do banco de dados MEDLINE, sendo selecionados os mais atuais e representativos do tema (2000-2006). Foram também pesquisados os sites do Centers for Disease Control and Prevention (CDC) e American Academy of Pediatrics (AAP), da Sociedade Brasileira de Pediatria (SBP) e do Ministério da Saúde do Brasil. SíNTESE DOS DADOS: A prevenção das hepatites virais é um enorme desafio para o sistema de saúde pública dos países e das comunidades médica e científica. Os vírus das hepatites ocasionam importante morbimortalidade no mundo, causando doença hepática aguda e crônica. Vacinas altamente eficazes estão disponíveis no mercado para prevenir novas infecções pelos vírus A e B. Entretanto, as hepatites virais A e B continuam a estar entre as doenças preveníveis por vacinas mais comumente notificadas. Neste artigo, revisamos as vacinas usadas para prevenir essas infecções com o objetivo de expandir o conhecimento e o uso da prevenção dessas doenças infecciosas. CONCLUSÃO: Embora as vacinas contra as hepatites A e B sejam recomendadas para vários grupos de risco, a cobertura vacinal estimada ainda é modesta e existem muitas oportunidades perdidas de vacinação. Para que haja diminuição na incidência das hepatites A e B, duas doenças preveníveis por vacinas, é necessário que os médicos incentivem seus pacientes a receber as vacinas.

Actualidad en hepatitis por virus A / Current situation in viral hepatitis A

La hepatitis por virus A (VHA) es una de las enfermedades más ampliamente difundidas en el mundo, generalmente aparece en forma de brotes epidémicos y se trasmite predominantemente por vía fecal oral, un tercio de los casos reportados por esta infección ocurre en niños y consta de varias formas clínicas de presentación; el tratamiento se basa en la aplicación de medidas generales así como la inmunoprofilaxis activa y pasiva, su elevada prevalencia en nuestro medio nos motiva a revisar la literatura reportada hasta hoy sobre el tema y resumir los aspectos más novedosos en cuanto a sus características y formas de evitarla.

Anti-hepatitis A virus frequency in adolescents at an outpatient clinic in São Paulo, Brazil

A prevalência de anticorpos contra o vírus da hepatite A foi avaliada em adolescentes de 10,4 a 19,9 anos atendidos no Ambulatório de Adolescentes da Universidade Federal de São Paulo. Entre 253 indivíduos analisados, a prevalência de anticorpos foi de 54,2%. Quando os adolescentes foram separados em duas faixas etárias, a prevalência foi maior no grupo de 15 a 19 anos (64%) em comparação com os de 10 a 14 anos (46%) (Qui-quadrado: p = 0,004). Estes resultados sugerem que muitos adolescentes de São Paulo estão sob risco de infecção pelo vírus da hepatite A e alguns deles estão provavelmente se infectando durante a adolescência.

Seguimientos de anticuerpos contra hepatitis A y E en una cohorte de niños de bajo nivel socioeconómico / Hepatitis A and E virus antibodies in Chilean children of low socioeconomic status. A one year follow-up study

Background: The seroprevalence of antibodies against hepatitis A virus (HAV) is decreasing in many Latin American countries, along with improvements in sanitary standards. However, there is no information available about low socioeconomic status (LSE) populations. Aim: To assess the evolution of hepatitis A and E virus antibodies in a cohort of LSE Chilean children. Material and methods: One hundred sixty eight children aged four years, 97 males, coming from public primary care clinics, were studied. Two blood samples were obtained with an interval of one year. Anti-HAV and anti-hepatitis E virus (HEV) antibodies, were detected by ELISA using Abbott kits. Results: Anti-HAV was positive in 19 children (11.3%). After one year of follow-up, only 10 children had sustained reactivity (52.6%). Fourteen children, initially negative, became positive during the follow up (9.4%). Antibody titers to HAV were significantly higher in samples that remained positive, compared with those that lost reactivity. Anti-HEV was found positive in two children (1.2%). One remained positive and the other became negative. Conclusions: In this cohort of LSE Chilean children, the prevalence to antibodies against HAV and HEV is low. Follow-up detected loss of reactivity to HAV in nearly one half of the children, probably related to lower antibody levels.

Prevalence of anti-hepatitis B and anti-hepatitis A antibodies among school aged children in Western Saudi Arabia

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. 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. 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. 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