Eficacia, seguridad y recomendaciones de uso de vacunas contra hepatitis A en niños expuestos e infectados por virus de inmunodeficiencia humana (VIH) / Efficacy, safety and usage recommendations of vaccines against hepatitis A in children exposed and infected by the immunodeficiency virus human (HIV)

ANTECEDENTES: La inmunización de niños infectados o expuestos al VIH representa una estrategia fundamental para reducir la morbilidad y mortalidad por enfermedades infecciosas prevenibles por vacunación, cuyo riesgo es marcadamente elevado en esta población debido al compromiso del sistema inmune. Sin embargo, una menor cantidad de niños con VIH logran inmunidad protectora y aquellos que lo hacen pueden experimentar una disminución mayor y más rápida de la inmunidad. La importancia de prevenir la infección por el virus de la hepatitis A (VHA) en el contexto de la coinfección con VIH radica en que la inmunosupresión asociada al VIH puede incrementar la duración, virulencia y patogenicidad del VHA, a su vez que la infección por VHA puede afectar el curso de la enfermedad por VIH. OBJETIVO: Describir la evidencia científica disponible en relación a la eficacia, seguridad y recomendaciones de uso de vacunas contra hepatitis A en niños expuestos e infectados por virus de inmunodeficiencia humana (VIH). OBJETIVO: Describir la evidencia científica disponible en relación a la eficacia, seguridad y recomendaciones de uso de vacunas contra hepatitis A en niños expuestos e infectados por virus de inmunodeficiencia humana (VIH). MÉTODO: Búsqueda electrónica de estudios publicados en español o inglés en PubMed, Cochrane Library, Web of Science y LILACS hasta el 27 de noviembre de 2021. Adicionalmente, se realizó una búsqueda en PubMed y repositorios de organismos elaboradores de Guías de Práctica Clínica. La selección de estudios fue desarrollada por un solo revisor. RESULTADOS: Se incluyeron diez estudios para la evaluación de la eficacia y seguridad y cuatro documentos para la evaluación de las recomendaciones de uso de vacunas contra hepatitis A en niños expuestos e infectados por virus de inmunodeficiencia humana (VIH). Seroprevalencia contra VHA al inicio del estudio: El porcentaje de participantes con presencia de anticuerpos contra VHA al inicio de estudio fue generalmente bajo (mediana: 12.2%; rango: 2.9% a 48.3%). Inmunogenicidad de las vacunas contra VHA: Tras una primera dosis de inmunización contra el VHA, la seroconversión se produjo en un 68.6% a 87.1% de participantes (mediana: 76.7%). Tras una segunda dosis, el porcentaje de seroconversión se ubicó en el rango de 84.5% a 100% (mediana: 98%). El porcentaje o recuento inicial de CD4 fue un importante predictor de la concentración de anticuerpos. Un único estudio evaluó el efecto de una tercera dosis de vacuna contra el VHA aplicada 18 meses después de la segunda dosis, obteniendo seropositividad de 97%, con un 76% con altos títulos de anticuerpos (≥ 250 mIU/mL). El título medio de anticuerpos fue mayor con tres dosis, comparado con dos dosis de vacuna (602 vs. 287 mUI / ml; p< 0,0001). Eventos adversos asociados a la vacunación: La vacunación contra el VHA en niños infectados o expuestos al VIH produjo eventos adversos leves y en su mayoría autolimitados. La carga viral media de VIH no varió en los niños con VIH vacunados. Duración de la protección después de la inmunización: Se evaluó la presencia de anticuerpos contra el VHA habiendo transcurrido 18 meses después de la aplicación de la segunda dosis de la vacuna. De 120 participantes, 108 (90%) tenían títulos de anticuerpos protectores persistentes, mientras que 12 (10%) no los tenían. Entre quienes no los tenían, dos participantes nunca presentaron respuesta protectora, nueve tuvieron títulos de anticuerpos de ≥ 20 a ≤ 250 mUI/mL tras la segunda dosis, y uno tuvo títulos de anticuerpos de 329 mUI/mL tras la segunda dosis. Los sujetos con bajas respuestas de anticuerpos después de dos dosis de la vacuna contra el VHA tuvieron menor probabilidad de mantener seropositividad 18 meses después que aquellos con altas respuestas de anticuerpos (p= 0.0003). Recomendaciones sobre la vacunación contra VHA en niños con VIH: El NIH de Estados Unidos, y el Ministerio de Salud y Protección Social de Colombia recomiendan dos dosis de vacunas contra VHA en niños con VIH a los 12 y 18 meses. El Ministerio de Salud Pública de Ecuador recomienda solo una dosis a los 12 meses. La Organización Mundial de la Salud recomienda la inmunización contra VHA con un esquema de dos dosis en grupos de riesgo de contraer hepatitis A e inmunodeprimidos. CONCLUSIONES: En los diferentes estudios, la seroprevalencia inicial de anticuerpos contra el virus de la hepatitis A (VHA) fue muy baja, con una mediana de 12.2%, lo cual indica una gran proporción de niños infectados o expuestos a VIH susceptibles a infección por VHA. La aplicación de una primera dosis de vacuna contra VHA produjo una mediana de seroconversión de 76.7%, mientras que una segunda dosis alcanzó una mediana de seroconversión del 98%. El estado inicial de linfocitos T CD4+ fue un importante predictor de la concentración de anticuerpos contra el VHA tras la inmunización. Un mayor recuento o porcentaje inicial de CD4 se asoció con mayor seroconversión, títulos de anticuerpos más altos y mayor probabilidad de mantener seropositividad 18 meses después de la segunda dosis. Resultados de un único estudio muestran que 18 meses después de la aplicación de la segunda dosis de la vacuna contra VHA, un 8.3% de niños dejaron de tener anticuerpos protectores contra el VHA. Resultados de un único estudio muestran que la aplicación de una tercera dosis de vacuna contra VHA 18 meses después de la segunda dosis no alteró el porcentaje personas con seroconversión, pero produjo mayores concentraciones de anticuerpos que quienes solo recibieron dos dosis. La vacunación contra el VHA en niños infectados o expuestos al VIH produjo eventos adversos leves y en su mayoría autolimitados. La carga viral media de VIH no varió en los niños con VIH vacunados. El NIH de Estados Unidos y el Ministerio de Salud y Protección Social de Colombia recomiendan dos dosis de vacunas contra VHA en niños con VIH a los 12 y 18 meses. El Ministerio de Salud Pública de Ecuador recomienda solo una dosis a los 12 meses. La Organización Mundial de la Salud recomienda la inmunización contra VHA con un esquema de dos dosis en grupos de riesgo de contraer hepatitis A e inmunodeprimidos.

Disparities in hepatitis A virus (HAV) vaccination coverage among adult travelers to intermediate or high-risk countries: The role of birthplace and race/ethnicity.

BACKGROUND: While the hepatitis A virus (HAV) vaccine is recommended for United States (US) travelers to endemic regions, vaccination rates are lower among non-US-born adults and some racial minority groups. PURPOSE: We aimed to examine the relationship between birthplace, race and their interaction as predictors of self-reported HAV vaccination among adult travelers to high-risk countries (HRCs) through analysis of the National Health Interview Survey (NHIS), 2012-2015. METHODS: The study included 36,872 US adult participants in the 2012-2015 NHIS who traveled to countries where HAV is endemic. The main outcome was self-reported HAV vaccination (≥2 doses). Complex survey methods were applied to all models to provide statistical estimates that were representative of US adults. Multivariable logistic regression models adjusting for demographic, socioeconomic, medical, and access-to-care characteristics were fitted to examine the association between birthplace, race, race-by-birthplace (for interaction) and vaccination status. RESULTS: For adult travelers to HRCs, the adjusted odds ratio (AOR) of HAV vaccination was lower for non-US-born compared to US-born adults, AOR 0.86 (95% CI; 0.76, 0.98). For Hispanics, the AOR of HAV vaccination was 0.80 (95% CI; 0.70, 0.91) as compared to non-Hispanic-Whites. Furthermore, a significant qualitative interaction between birthplace and race was found (P-value 0.0005). Among non-Hispanic Blacks, the adjusted odds of HAV vaccination for non-US-born adults were 1.35 (95% CI; 1.06, 1.72) times the odds for US-born adults. In contrast, the AORs of HAV vaccination of non-US-born versus US-born adults were 36% (95% CI; 17%, 51%) and 30% (95% CI; 12%, 44%), lower for Asians and Hispanics, respectively. CONCLUSIONS: The association between birthplace and HAV vaccination status differs by race among travelers to HRCs, with US-born non-Hispanic Black and non-US-born Asian and Hispanic adults having lower odds of vaccination. Health care resources should be focused on these target populations to improve travel vaccination compliance.

Challenges in Management of Hepatitis A Virus Epidemiological Transition in Mexico.

Hepatitis A virus (HAV) is the most common cause of acute viral hepatitis worldwide. The virus is mainly transmitted via the fecaloral route and, the incidence of infection is closely related to low socioeconomic conditions and poor sanitation. Mexico, previously categorized an area of high endemicity for HAV infection, is undergoing epidemiological transition. However, a limited number of HAV-related scientific reports regarding to virus burden is available. According to the local government health agency (Secretarla de Salud, SSA in Spanish), from 1994 to 2017 a reduction in the incidence of hepatitis related to HAV has been reported. However, HAV is still the most common cause of viral hepatitis in the country, and the pediatric population is the most prone to be infected with this virus. The analysis of the SSA data reveals that most of the reported cases from 1994 to 2017 were found in highly industrialized states. This information contradicts the documented relationship between the highest prevalence of infection and the lowest socio-economic status, and supports the necessity of viral detection and notification of HAV cases. Moreover, in spite that four HAV vaccines are available in Mexico and universal vaccination has been shown to be beneficial in developing countries in terms of declining endemicity, HAV vaccination is not mandatory in Mexico. In this review, preventive strategies including appropriate diagnosis, vaccination and public health policies on the basis of the epidemiologic status of HAV in Mexico are discussed.

Seroepidemiology of HEV and HAV in two populations with different socio-economic levels and hygienic/sanitary conditions.

The epidemiological scenarios of hepatitis E virus (HEV) and hepatitis A virus (HAV) infections have changed in the last few decades, but precise epidemiological data on the prevalence of anti-HEV and anti-HAV, alone or in combination, in the general population are scanty. We investigated HEV and HAV seroprevalence comparing two population samples living in Northern (Abbiategrasso, Milan) and Southern Italy (Cittanova, Reggio Calabria), the latter being characterized by a poorer socio-economic level and hygienic/sanitary conditions. Based on census records, we randomly enrolled and tested 3,365 subjects (Abbiategrasso, n = 2,489; Cittanova, n = 876) aged 18-75 years for anti-HAV and anti-HEV. Anti-HAV (71.3 % vs 52.5 %) and anti-HEV (17.8 % vs 9.0 %) prevalence rates were higher in Southern Italy (both p < 0.001). Most anti-HEV-positive subjects also had anti-HAV. Subjects testing positive for anti-HAV, alone or with anti-HEV, were older (p < 0.001 in both populations) and showed a trend toward declining prevalence in the youngest birth cohorts. The prevalence of subjects with a positive result for anti-HEV alone did not change in birth cohorts in the two towns. Detection of anti-HEV was independently associated with anti-HAV, town, birth cohort, and education level in multivariate analysis. Low socio-economic level and hygienic/sanitary conditions are associated with high HAV and HEV seroprevalence rates in Italy. Recent improvements, especially in the South, have led to a declining prevalence of anti-HAV, alone or with anti-HEV. Seroprevalence of HEV alone is uniformly low and does not change in birth cohorts born between 1938 and 1993.

Seroprevalence and predictors of hepatitis A infection in Nigerian children.

INTRODUCTION: Hepatitis A infection is prevalent in developing countries where sanitation is still a public health issue. In Nigeria, there is no epidemiological data on children for this infection. A community based study was carried out to establish the seroprevalence and predictors of this infection in children. METHODS: A community based cross sectional study was carried out in Akpabuyo local Government Area of Cross River State in southern Nigeria. Multi-staged sampling technique was used to recruit 406 children aged 1-18 years. Blood samples were analysed for anti-HAV total antibody (IgM and IgG) using a commercial Enzyme-Linked Immunoassay Assay(ELISA). A multivariate logistic regression was used to identify factors that independently predicted the occurrence of anti-HAV total antibody. p value of < 0.05 was considered significant. RESULTS: Two hundred and twenty four subjects tested positive for anti-HAV total antibody giving a prevalence rate of 55.2%. The median age for those positive was 9 years and for those without evidence of HAV infection was 4 years. One hundred and one (45.1%) males and 123 (54.9%) females were positive. The study population was mainly of the low social class with 94.1%. After multivariate analysis, predictors of HAV infection were age and social class. CONCLUSION: HAV infection was prevalent in the study population. Educational campaign is imperative and vaccine provision is advocated to further curb the spread of this infection.

Role of CD4 count in immunity development after hepatitis A and B vaccination among HIV-infected patients: Kentucky, 2002-2007.

PURPOSE: To determine whether lower prevaccination CD4 counts decrease odds of immune development against hepatitis A virus/hepatitis B virus (HAV/HBV) among patients who receive the vaccine and examine the relationship between vaccine response and sex, race/ethnicity, health insurance status, tobacco use, substance abuse, or comorbidities. METHODS: This study was performed among patients who received the standard dose for HAV and/or HBV vaccine. RESULTS: Among 76 HIV-infected patients, immunity development to HAV or HBV increased as CD4 counts increased. In addition, males had greater vaccine response than females. Whites were observed to have higher rates of immunity than other races/ethnicities. Patients with private insurance had greater vaccine response than those with Medicaid, Medicare, or no insurance. Patients not experiencing hypertension and hyperlipidemia developed immunity more often than patients with these comorbidities. Substance abuse and tobacco use were also associated with lower vaccine response. CONCLUSIONS: Higher CD4 counts improved likelihood of patients developing an antibody response after vaccination.

Evidence of vaccine protection among thai medical students and implications for occupational health.

In a cross-sectional study of Thai medical students, we compared the seroprevalence of antibody to measles virus, rubella virus, varicella zoster virus, hepatitis A virus, and hepatitis B virus with self-reports of prior infection or vaccination. Self-report predicted immunity to varicella zoster virus only. These data contribute to risk assessment and occupational health strategies in this resource-limited setting.

Should Brazilian patients with chronic hepatitis C virus infection be vaccinated against hepatitis A virus?

BACKGROUND AND AIM: Hepatitis A virus (HAV) superinfection is associated with a high risk of liver failure and death in patients with hepatitis C virus (HCV) infection. The aim of this study was to investigate the presence of serological and molecular HAV markers in a population of HCV-infected patients in order to determine a cost-effective strategy to vaccinate against HAV. METHODS: The presence of total and immunoglobulin (Ig)M anti-HAV antibodies was investigated in 399 patients (median age, 50 years; range, 4-81) referred to the Public Health Central Laboratory of Pernambuco State who tested positive for anti-HCV antibodies and HCV RNA. HAV RNA was investigated by reverse transcription-nested polymerase chain reaction in these patients. RESULTS: Three hundred and eighty-four (96%) patients were positive for anti-HAV total and negative for IgM anti-HAV antibodies (immune patients). Three patients had IgM (and total) anti-HAV antibodies, showing an acute infection, and two of them had HAV RNA detected in serum samples. HAV RNA was also found in another patient in the absence of detectable anti-HAV antibodies. By nucleotide sequencing, it was demonstrated that the HAV isolates infecting these patients belonged to subgenotype 1B. CONCLUSION: This study provides valuable new data on anti-HAV prevalence among HCV carriers in Brazil. In the present study, we found a high proportion of patients with anti-HAV positivity, indicating that anti-HAV testing of HCV-infected patients is a cost-effective strategy and should be carried out before vaccination against HAV in these patients, particularly in regions such as our geographical area with high total anti-HAV prevalence.

High prevalence of hepatitis A virus antibody among Bangladeshi children and young adults warrants pre-immunization screening of antibody in HAV vaccination strategy.

Serum samples from 465 subjects aged between 1 and 25 years were tested for antibody against hepatitis A virus (HAV) [anti-HAV IgG and IgM] to determine the seroprevalence of HAV antibody and do a cost-benefit analysis for decision making about vaccination against HAV among the general population of Bangladesh. A high prevalence of anti-HAV (74.8%) was observed in the study population; the whole study population was found positive for anti-HAV by the age of 25 years. On performing the cost-benefit analysis, it was found that the cost for vaccination with screening for anti-HAV was almost three times cheaper than vaccination without screening. Thus, in the present socioeconomic condition of Bangladesh, a policy based on screening for HAV antibody before vaccination is recommended.

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

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

[Is it necessary to investigate anti-hepatitis A virus (HAV) IgM antibodies when the hepatic enzymogram is normal?]. / Es necesario investigar anticuerpos IgM contra el virus de la hepatitis A cuando el enzimograma hepático es normal?

Is it necessary to investigate anti-hepatitis A virus (HAV) IgM antibodies when the hepatic enzymogram is normal? Type A viral Hepatitis (HAV) is the most frequent viral hepatitis around the world, especially in low income countries. In order to confirm this disease, a lot of laboratory tests are annually carried out where HAV is endemic. Our objective was to establish the utility of investigating anti-hepatitis A virus (HAV) IgM antibodies for HAV diagnosis in patients with normal levels of serum aspartate and alanine aminotransferases (AST/ALT). All patients (n = 158) received in the laboratory requesting a hepatic enzymograme and anti-HAV IgM were evaluated in a prospective study between October 2005 and March 2006. Anti-HAV IgM assays were carried out by microparticle enzyme immunoassay (MEIA). The quantification of hepatic enzymes was made in a multianalyzer. The most frequent clinical data were: presumption of hepatitis and jaundice (27.5 and 12.7%). Eighty four of the 158 patients (53%) showed elevated values of ALT and AST, whereas 69 patients in this group (82%) were anti-Hav IgM reactive. The remaining 74 patients (47%) showed normal levels of AST/ALT and none of them were anti-HAV IgM reactive, except 7, who were on control of a confirmed HAV infection. Of the anti-HAV IgM reactive group of patientss, 49% were children under 10 years of age. Laboratory HAV confirmatory tests would have to be made in sequential form, the determination of anti-HAV IgM antibodies being unnecessary when normal values of serum aminotransferases are observed.

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

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

The cost-effectiveness of two strategies for vaccinating US veterans with hepatitis C virus infection against hepatitis A and hepatitis B viruses.

OBJECTIVES: Although hepatitis A and B vaccinations are recommended for patients with chronic hepatitis C virus (HCV), the ideal vaccination strategy has not been determined. Our objective was to model the cost-effectiveness of two strategies for vaccinating patients with HCV infection against hepatitis A (HAV) and hepatitis B (HBV) viruses. The strategies evaluated were: universal vaccination with the combined HAV and HBV vaccine, and selective vaccination based on immunity determined by blood testing. METHODS: A decision tree model was constructed to compare the cost-effectiveness of the two vaccination strategies from the New Mexico Veterans Affairs Health Care System (NMVAHCS) perspective. A retrospective review of all HCV patients (2517 subjects) at the NMVAHCS was performed to extract prevalence of immunity to HAV and HBV, and prevalence of decompensated liver disease. Literature review was performed to obtain other probabilities for the model. Only direct medical costs were considered; the effectiveness measure was the number of patients immune to both HAV and HBV. Sensitivity analyses were performed to test robustness of the results to changes in input variables. All costs were in 2004 US dollars. RESULTS: The selective strategy was less costly but less effective, with a cost-effectiveness ratio of 105 dollars per patient immune to HAV and HBV. The universal strategy was more effective but more expensive with a cost-effectiveness ratio of 112 dollars per patient immune to HAV and HBV. Compared with the selective strategy, universal strategy was associated with an incremental cost-effectiveness (ICE) ratio of 154 dollars per additional patient immune to HAV and HBV. The universal strategy would become more cost-effective if 1) the cost of combined vaccine was reduced to less than 30.75 dollars (9.7% reduction), 2) the cost of HBV vaccine increased to greater than 34.50 dollars (25% increase), 3) the cost of blood tests for immunity increased to more than 25.25 dollars (23% increase), or (4) the prevalence of anti-HBs decreased to less than 24%. CONCLUSIONS: The selective vaccination strategy for HAV and HBV in our sample of patients with HCV is more cost-effective. However, the universal strategy is more effective and its ICE is minimal, thus it may be worth the additional cost.

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

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.

Hepatitis A virus: from discovery to vaccines.

Hepatitis A virus (HAV), the causative agent of type A viral hepatitis, is an ancient human virus that was first identified almost 35 years ago. It has several characteristics that make it unique among the Picornaviridae, particularly in terms of its mechanisms of polyprotein processing and virion morphogenesis, and which likely contribute to its pathobiology. Although efficacious vaccines containing formalin-inactivated virus produced in cell culture have been licensed in multiple countries, their use has been limited by cost considerations. Changes in public health sanitation and generally increasing standards of living are leading to a decreasing incidence of acute hepatitis A worldwide, with the result that the prevalence of preexisting immunity among adults is declining in many regions. These changes in the epidemiology of HAV may paradoxically enhance the disease burden, as greater numbers of individuals become infected at older ages when disease is more likely to be clinically evident, thus providing greater incentives for vaccine utilization.

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.

Immunogenicity and reactogenicity of a combined hepatitis A and B vaccine in healthy Chilean subjects.

OBJECTIVES: A combination vaccine against hepatitis A and B provides the opportunity for simultaneous protection against both diseases with a single vaccine. This clinical study investigated the reactogenicity and immunogenicity of a combined hepatitis A and B vaccine (Twinrix, GlaxoSmithKline Biologicals, Rixensart, Belgium) in healthy Chilean adults between 18 and 40 years of age. METHODS: In total, 345 healthy, seronegative health care workers were enrolled and randomized to three groups who received one of three lots of Twinrix on a 0-, 1- and 6-month schedules. Blood samples were screened 1 month after each dose for anti-HAV and anti-HBs antibodies. Reactogenicity after each dose was assessed using diary cards. RESULTS: The nature and incidence of symptoms were similar to those reported for other Twinrix studies. Very few symptoms were scored as severe. Upon completion of the vaccination, all subjects had anti-HAV antibodies with titers $6000 mIU/mL, and all but one were protected against hepatitis B, with titers $4000 mIU/mL. CONCLUSIONS: We have demonstrated the high immunogenicity and tolerance of the combined hepatitis A and B vaccine. Combined vaccination has the advantage of offering dual protection with a reduction in the number of injections needed, lower associated costs, and a positive impact on compliance.