Updating the knowledge of hepatitis E: new variants and higher prevalence of anti-HEV in Argentina.

INTRODUCTION: Hepatitis E is a disease of global distribution, with significant morbidity and mortality, whose scope and burden continue to emerge in low endemic countries. MATERIAL AND METHODS: In 2012, we studied the prevalence of anti-HEV antibodies in 202 adult serum samples. We also analyzed samples from 143 patients with acute non-A-C hepatitis from January 2011 to December 2013. Acute HEV infections were diagnosed with anti-HEV IgM and/or HEV RNA. HEV RNA was also investigated in 94 swine fecal samples. HEV RNA was sequenced and characterized. RESULTS: We found higher values of prevalence than those previously reported in the 1990s. The overall prevalence of anti-HEV IgG antibodies was 15.4%. The prevalence was 10.6% in the 123 adults voluntarily screened on World Hepatitis Day 2012 in Buenos Aires city and 14.8, 16.7 and 35.7% respectively in the smaller groups of healthcare workers, blood donors and HIV-positive patients from different regions of the country. Nine acute HEV infections were diagnosed in the three years analyzed. We characterized new human variants of subgenotype 3a and 3i. New subgenotype 3i variants were found in swine from two distant provinces closely related to the human ones. CONCLUSIONS: These results enlarge the knowledge of HEV and contribute with new information. However, higher values of prevalence found in small groups need to be confirmed in larger studies. Many aspects of the spectrum of the disease and the reservoirs and routes of transmission are still unknown and thus deserve additional research.

Identifications of polyphyletic variants in acute hepatitis suggest an underdiagnosed circulation of hepatitis E virus in Argentina.

BACKGROUND: In recent years, an increasing number of infections with genotype 3 hepatitis E virus (HEV) have been reported in western countries. Data in South America, however, are still scarce. Swine and human variants previously described in Argentina are closely related to a human Austrian one. OBJECTIVE: To identify whether HEV is still circulating in Argentina. STUDY DESIGN: Sera and stool samples from adults and children with unexplained acute liver disease referred to our center during the last six years were prospectively studied. Dual infection with hepatitis A was retrospectively studied in a group of children with fulminant hepatic failure. RESULTS: Fifteen new cases (13 adults and 2 children), seven of whom required hospitalization, were diagnosed. Nine had detectable HEV RNA, and one had imported genotype 1. Subgenotype 3i HEV-related variants are still circulating. Five autochthonous sequences, related to European, American and Japanese ones, grouped in subgenotype 3a. One case had a subgenotype 3b variant. DISCUSSION: The polyphyletic variants widespread in Argentina suggest multiple sources of infection. Whether or not their reservoir is swine merits further investigation. Since hepatitis E is still considered rare, differential laboratory testing in unexplained acute liver disease is not routinely performed in Argentina. Broadening awareness of this disease is important in light of the decrease in hepatitis A incidence since universal vaccination was implemented in 2005. The diagnosis of hepatitis E with a combination of serological and molecular tools is needed to better understand its epidemiology and impact on the clinical management of patients with unexplained increased transaminases.

A polymorphism in TIM1 is associated with susceptibility to severe hepatitis A virus infection in humans.

During infection with the hepatitis A virus (HAV), most patients develop mild or asymptomatic disease. However, a small number of patients develop serious, life-threatening hepatitis. We investigated this variability in disease severity by examining 30 Argentinean patients with HAV-induced acute liver failure in a case-control, cross-sectional, observational study. We found that HAV-induced severe liver disease was associated with a 6-amino-acid insertion in TIM1/HAVCR1 (157insMTTTVP), the gene encoding the HAV receptor. This polymorphism was previously shown to be associated with protection against asthma and allergic diseases and with HIV progression. In binding assays, the TIM-1 protein containing the 157insMTTTVP insertion polymorphism bound HAV more efficiently. When expressed by human natural killer T (NKT) cells, this long form resulted in greater NKT cell cytolytic activity against HAV-infected liver cells, compared with the shorter TIM-1 protein without the polymorphism. To our knowledge, the 157insMTTTVP polymorphism in TIM1 is the first genetic susceptibility factor shown to predispose to HAV-induced acute liver failure. Furthermore, these results suggest that HAV infection has driven the natural selection of shorter forms of the TIM-1 protein, which binds HAV less efficiently, thereby protecting against severe HAV-induced disease, but which may predispose toward inflammation associated with asthma and allergy.

Clinical implications of hepatitis A virus ribonucleic acid detection and genotyping in acute liver failure in children in Argentina.

OBJECTIVES: To investigate the detection of hepatitis A virus ribonucleic acid in patients with acute liver failure and to assess if the results have any clinical implications for the evolution of acute liver failure in children. Hepatitis A infection, a vaccine-preventable disease, is an important cause of acute liver failure in children in Argentina. Universal vaccination in 1-yr-old children was implemented in June 2005. DESIGN: Observational study in which patients were divided into Group 1 consisting of positive hepatitis A virus ribonucleic acid and Group 2 consisting of negative hepatitis A virus ribonucleic acid. SETTING: Pediatric intensive care unit in National Pediatric Hospital "Dr. J. P. Garrahan," Buenos Aires, Argentina. PATIENTS: Thirty-three patients with the diagnosis of acute liver failure secondary to hepatitis A virus infection and admitted to the Garrahan Pediatric Hospital between September 2003 and September 2005 were enrolled in the study. Twenty of these children were admitted to the pediatric intensive care unit. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Samples for total ribonucleic acid detection and genotyping were obtained from serum and/or stools on admission. We found positive hepatitis A virus ribonucleic acid in 13 patients and negative hepatitis A virus ribonucleic acid in 20 patients. The following clinical variables were evaluated: time of evolution, hospital stay, admission to the pediatric intensive care unit, pediatric intensive care unit stay, time on mechanical ventilation, criteria for orthotopic liver transplantation, and mortality. Characterization of the isolates did not reveal differences related to genotype; all cases were IA. No statistical significance was found as to the variables. However, positive hepatitis A virus ribonucleic acid showed lower percentages of pediatric intensive care unit admissions, criteria for orthotopic liver transplantation, number of orthotopic liver transplantation, and mortality than the group of patients with negative hepatitis A virus ribonucleic acid. CONCLUSIONS: Hepatitis A virus genotyping studies did not show any particularities, all cases were IA and, thus, apparent associations between genotype and the clinical presentation of acute liver failure could not be found.

Molecular characterization of hepatitis A virus in children with fulminant hepatic failure in Argentina.

BACKGROUND: Hepatitis A infection, a vaccine-preventable disease, is an important cause of fulminant hepatic failure (FHF) in children in Argentina. Universal vaccination in 1-year-old children was implemented in June 2005. The limited studies about the correlation between the characteristics of the hepatitis A virus (HAV) and FHF have been carried out in adults. METHODS: Samples from 41 children with FHF were studied from September 2003 to January 2006 and HAV RNA was detected, sequenced and analysed in the 5' non-coding region and VP1/2A region. RESULTS: Eighteen HAV strains were characterized and found to be different at the nucleotide level from the self-limited acute infection strains that have been circulating in Argentina with no temporal or geographical pattern. They did not form a genetic cluster, but some of them were identical in the largest fragment characterized and some of them seemed to be more closely related in time and/or geographically. CONCLUSION: Our results suggest that viral factors could be involved in the severity of the clinical presentation of HAV infection in children in Argentina.

Molecular characterization of hepatitis A virus isolates from Argentina.

Hepatitis A, a vaccine preventable disease, is now of transitional or intermediate endemicity in Argentina, as the epidemiologic pattern of the disease has shifted with improvements in living conditions in some parts of the country. Increase in the susceptibility of older children and adults has led to increasing disease incidence. Molecular epidemiology has played an important role in the understanding of HAV infection by identifying modes of spreading and by permitting the monitoring of changes in circulating virus brought about by prevention programs. South American isolates characterized are limited. Eighty-two sporadic and outbreak isolates from Argentina were sequenced in the VP1/2A region of HAV genome over a 9-year period. All the isolates belonged to subgenotype IA. All our sequences grouped into two big clusters. Apparently, at least two lineages have been co-circulating in the same place at the same time. Despite great genetic variability, few point amino acid changes could be deduced. Four sequences showed an Arg --> Lys substitution at 1-297 which characterized the genotype IB at the amino acid level. Many isolates carried a conservative amino acid substitution Leu --> Ile at position 42 of the 2A domain, previously described as a possible fingerprint of HAV sequences in Brazil. The other rare changes have been found before, except for a 1-277 Asn --> Ser substitution displayed in two isolates that has not been previously reported. Argentina recently implemented universal vaccination in 1-year-old children. Molecular tools would be useful in an active surveillance program.

Duración de la viremia y la excreción fecal del virus en niños con Hepatitis A / Duration of viremia and fecal shedding of the virus in Hepatitis A infected children

La infección por el virus de hepatitis A (HAV) es endémica en Argentina. El uso de técnicas moleculares permitió extender la detección del RNA del HAV en sueroy heces en pacientes con diferentes presentaciones clínicas. Comparamos la sensibilidad del protocolo de RT-PCR que usamos con cebadores dirigidos a distintas regiones del genoma, resultando la detección de la región VP3 C terminal la más sensible. Se obtuvieron prospectivamente muestras de suero y materia fecal de 20 niños con hepatitis aguda autolimitada por HAV. El RNA del HAV fue detectado en 18/20 niños en muestras basales y en 19/20 sumando una muestra posterior. El RNA del HAV fue detectable en 9/20 acientes hasta 30 días en suero; en materia fecal en 2/20 hasta 60 días y en 1/20 hasta 90 días. La secuencia genómica para la región VP1/2A en 8 muestras demostró que todas pertenecían al subgenotipo IA, aunque eran diferentes entre sí. Solo en 1/11 niños con falla hepatica fulminante fue posible la detección del RNA del HAV utilizando la región VP3 C terminal y el genotipo fue I. La reciente introducción de la vacunación universal en niños de 1 año de edad en Argentina podría disminuir drásticamente la circulación del virus, emergiendo nuevas fuentes de infección y permitiendo la introducción de nuevos genotipos. Las técnicas moleculares aplicadas al estudio de la historia natural de la infección y a la vigilancia epidemiológica contribuyenal control y la toma de decisiones eficientes en políticas de Salud Pública.

Hepatitis A virus (HAV) infection is endemic in Argentina. Molecular tools have allowed HAV RNA detection to be extent to sera and feces from patients with different clinical backgrounds. We compare the sensitivity of the RT-PCR protocol we follow using primers targeting different genomic regions and VP3 C terminal was the most sensitive. Sequential sera and fecal samples were obtained from 20 children with acute self limited Hepatitis A. HAV RNA was detectable in 18/20 children if sera and stool specimens were collected at the onset of symptoms and in 19/20 if a later sample was considered. HAV RNA was detectable in serum from 9/20 patients until day 30 and in feces from 2 patients until day 60 and until day 90 in one. Genomic sequences from VP1/2A region in 8 samples showed they all belong to subgenotype IA although they were different between them. HAV RNA was detectable only in 1/11 sera from children with acute liverfailure when VP3 C terminal fragment was searched and it belonged to genotype I. Universal vaccination in one year old children was recently implemented in Argentinaand it will dramatically enable the decrease of the viral circulation, making new sources of infection emerge and allowing the introduction of new genotypes. The application of molecular tools to the study of the natural history of infection and to the epidemiologicsurveillance may contribute to efficient control and lead to rational decisions in public health policies.

Duración de la viremia y la excreción fecal del virus en niños con Hepatitis A / Duration of viremia and fecal shedding of the virus in Hepatitis A infected children

La infección por el virus de hepatitis A (HAV) es endémica en Argentina. El uso de técnicas moleculares permitió extender la detección del RNA del HAV en sueroy heces en pacientes con diferentes presentaciones clínicas. Comparamos la sensibilidad del protocolo de RT-PCR que usamos con cebadores dirigidos a distintas regiones del genoma, resultando la detección de la región VP3 C terminal la más sensible. Se obtuvieron prospectivamente muestras de suero y materia fecal de 20 niños con hepatitis aguda autolimitada por HAV. El RNA del HAV fue detectado en 18/20 niños en muestras basales y en 19/20 sumando una muestra posterior. El RNA del HAV fue detectable en 9/20 acientes hasta 30 días en suero; en materia fecal en 2/20 hasta 60 días y en 1/20 hasta 90 días. La secuencia genómica para la región VP1/2A en 8 muestras demostró que todas pertenecían al subgenotipo IA, aunque eran diferentes entre sí. Solo en 1/11 niños con falla hepatica fulminante fue posible la detección del RNA del HAV utilizando la región VP3 C terminal y el genotipo fue I. La reciente introducción de la vacunación universal en niños de 1 año de edad en Argentina podría disminuir drásticamente la circulación del virus, emergiendo nuevas fuentes de infección y permitiendo la introducción de nuevos genotipos. Las técnicas moleculares aplicadas al estudio de la historia natural de la infección y a la vigilancia epidemiológica contribuyenal control y la toma de decisiones eficientes en políticas de Salud Pública.(AU)

Hepatitis A virus (HAV) infection is endemic in Argentina. Molecular tools have allowed HAV RNA detection to be extent to sera and feces from patients with different clinical backgrounds. We compare the sensitivity of the RT-PCR protocol we follow using primers targeting different genomic regions and VP3 C terminal was the most sensitive. Sequential sera and fecal samples were obtained from 20 children with acute self limited Hepatitis A. HAV RNA was detectable in 18/20 children if sera and stool specimens were collected at the onset of symptoms and in 19/20 if a later sample was considered. HAV RNA was detectable in serum from 9/20 patients until day 30 and in feces from 2 patients until day 60 and until day 90 in one. Genomic sequences from VP1/2A region in 8 samples showed they all belong to subgenotype IA although they were different between them. HAV RNA was detectable only in 1/11 sera from children with acute liverfailure when VP3 C terminal fragment was searched and it belonged to genotype I. Universal vaccination in one year old children was recently implemented in Argentinaand it will dramatically enable the decrease of the viral circulation, making new sources of infection emerge and allowing the introduction of new genotypes. The application of molecular tools to the study of the natural history of infection and to the epidemiologicsurveillance may contribute to efficient control and lead to rational decisions in public health policies.(AU)

[Duration of viremia and fecal shedding of the virus in hepatitis A infected children]. / Duración de la viremia y lla excreción fecal del virus en niños con hepatitis A.

Hepatitis A virus (HAV) infection is endemic in Argentina. Molecular tools have allowed HAV RNA detection to be extent to sera and feces from patients with different clinical backgrounds. We compare the sensitivity of the RT-PCR protocol we follow using primers targeting different genomic regions and VP3 C terminal was the most sensitive. Sequential sera and fecal samples were obtained from 20 children with acute self limited Hepatitis A. HAV RNA was detectable in 18/20 children if sera and stool specimens were collected at the onset of symptoms and in 19/20 if a later sample was considered. HAV RNA was detectable in serum from 9/20 patients until day 30 and in feces from 2 patients until day 60 and until day 90 in one. Genomic sequences from VP1/2A region in 8 samples showed they all belong to subgenotype IA although they were different between them. HAV RNA was detectable only in 1/11 sera from children with acute liver failure when VP3 C terminal fragment was searched and it belonged to genotype I. Universal vaccination in one year old children was recently implemented in Argentina and it will dramatically enable the decrease of the viral circulation, making new sources of infection emerge and allowing the introduction of new genotypes. The application of molecular tools to the study of the natural history of infection and to the epidemiologic surveillance may contribute to efficient control and lead to rational decisions in public health policies.

[Molecular characterization of hepatitis E virus in three acute liver failure cases in children in Argentina]. / Caracterización molecular del virus de hepatitis E en tres casos de falla hepática fulminante en niños de Argentina.

Strains of hepatitis E virus (HEV) isolated from Argentinian patients with sporadic hepatitis, as well as from swine from Argentina, belong to genotype 3. HEV genotype 3 variants have been described associated with acute liver failure (ALF) in adults from Japan and the United Kingdom. In Argentina, 30% of ALF in adults and children are of unknown aetiology. To study if HEV could be an aetiological agent associated with ALF in children, serum and/or fecal samples fJom 35 children (mean age: 6 years, 20 female, 15 male) were analyzed during 2003 and 2004. HEV RNA was detected by RT-nested PCR with primers designed within ORF 1 and ORF 2 regions. HEV RNA could be detected in three cases. Two were 12-year-old boys fom Buenos Aires province and the third was a 3-year-old girl from Corrientes province. Sequence analysis indicates that the three isolates are distinct from each other but all belong to genotype 3, exhibiting a close relationship with swine and human strains fJom sporadic cases of HEV, previously reported in Argentina. This data suggests a potential link between ALF and HEVin children in Argentina and indicates the need for the determination of HEV status in the differential diagnosis in ALE Further studies would aid in determining the true impact of this infection in Argentina and the potential benefits of a vaccine against HEV presently in phase III trials.

Caracterización molecular del virus de hepatitis E en tres casos de falla hepática fulminante en niños de Argentina / Molecular characterization of hepatitis E virus in three acute liver failure cases in children in Argentina

Las cepas de virus de hepatitis E (HEV) encontradas en casos esporádicos humanos y en cerdos en Argentina corresponden al genotipo 3. Se han descripto variantes de este genotipo asociadas a fallas hepáticas fulminantes (FHF) en adultos de Japón e Inglaterra. En Argentina el 30% de las FHF en adultos y en niños es de etiología desconocida. Para estudiar si el HEV podría ser el agente etiológico asociado a FHF en niños se analizaron el suero y/o la materia fecal de 35 niños (edad media 6 años, 20 mujeres, 15 varones) durante 2003 y 2004. El HEV RNA fue detectado por RT-nested PCR con cebadores dirigidos a las regiones ORF 1 y ORF 2. El HEV RNA pudo detectarse en 3 casos. Dos eran varones de 12 años residentes en la provincia de Buenos Aires y el tercero, una niña de 3 años de la provincia de Corrientes. El análisis de las secuencias muestra que las 3 variantes son distintas, pero pertenecen todas al genotipo 3 y están muy relacionadas a las cepas encontradas previamente en casos esporádicos en humanos y en cerdos de Argentina. Estos datos sugieren una posible relación entre FHF y HEV en niños de Argentina e indican la necesidad de considerar la infección con HEV en el diagnóstico diferencial de las FHF. Se necesitan más estudios que demuestren el verdadero impacto de esta infección y el beneficio potencial de na vacuna para HEV, actualmente en fase III.

Strains of hepatitis E virus (HEV) isolated from Argentinian patients with sporadic hepatitis, as well as from swine from Argentina, belong to genotype 3. HEV genotype 3 variants have been described associated with acute liver failure (ALF) in adults from Japan and the United Kingdom. In Argentina, 30% of ALF in adults and children are of unknown aetiology. To study if HEV could be an aetiological agent associated with ALF in children, serum and/or fecal samples from 35 children (mean age: 6 years, 20 female, 15 male) were analyzed during 2003 and 2004. HEV RNA was detected by RT-nested PCR with primers designed within ORF 1 and ORF 2 regions. HEV RNA could be detected in three cases. Two were 12-year-old boys from Buenos Aires province and the third was a 3- year-old girl from Corrientes province. Sequence analysis indicates that the three isolates are distinct from each other but all belong to genotype 3, exhibiting a close relationship with swine and human strains from sporadic cases of HEV, previously reported in Argentina. This data suggests a potential link between ALF and HEV in children in Argentina and indicates the need for the determination of HEV status in the differential diagnosis in ALF. Further studies would aid in determining the true impact of this infection in Argentina and the potential benefits of a vaccine against HEV, presently in phase III trials.

Caracterización molecular del virus de hepatitis E en tres casos de falla hepática fulminante en niños de Argentina / Molecular characterization of hepatitis E virus in three acute liver failure cases in children in Argentina

Las cepas de virus de hepatitis E (HEV) encontradas en casos esporádicos humanos y en cerdos en Argentina corresponden al genotipo 3. Se han descripto variantes de este genotipo asociadas a fallas hepáticas fulminantes (FHF) en adultos de Japón e Inglaterra. En Argentina el 30% de las FHF en adultos y en niños es de etiología desconocida. Para estudiar si el HEV podría ser el agente etiológico asociado a FHF en niños se analizaron el suero y/o la materia fecal de 35 niños (edad media 6 años, 20 mujeres, 15 varones) durante 2003 y 2004. El HEV RNA fue detectado por RT-nested PCR con cebadores dirigidos a las regiones ORF 1 y ORF 2. El HEV RNA pudo detectarse en 3 casos. Dos eran varones de 12 años residentes en la provincia de Buenos Aires y el tercero, una niña de 3 años de la provincia de Corrientes. El análisis de las secuencias muestra que las 3 variantes son distintas, pero pertenecen todas al genotipo 3 y están muy relacionadas a las cepas encontradas previamente en casos esporádicos en humanos y en cerdos de Argentina. Estos datos sugieren una posible relación entre FHF y HEV en niños de Argentina e indican la necesidad de considerar la infección con HEV en el diagnóstico diferencial de las FHF. Se necesitan más estudios que demuestren el verdadero impacto de esta infección y el beneficio potencial de na vacuna para HEV, actualmente en fase III.(AU)

Strains of hepatitis E virus (HEV) isolated from Argentinian patients with sporadic hepatitis, as well as from swine from Argentina, belong to genotype 3. HEV genotype 3 variants have been described associated with acute liver failure (ALF) in adults from Japan and the United Kingdom. In Argentina, 30% of ALF in adults and children are of unknown aetiology. To study if HEV could be an aetiological agent associated with ALF in children, serum and/or fecal samples from 35 children (mean age: 6 years, 20 female, 15 male) were analyzed during 2003 and 2004. HEV RNA was detected by RT-nested PCR with primers designed within ORF 1 and ORF 2 regions. HEV RNA could be detected in three cases. Two were 12-year-old boys from Buenos Aires province and the third was a 3- year-old girl from Corrientes province. Sequence analysis indicates that the three isolates are distinct from each other but all belong to genotype 3, exhibiting a close relationship with swine and human strains from sporadic cases of HEV, previously reported in Argentina. This data suggests a potential link between ALF and HEV in children in Argentina and indicates the need for the determination of HEV status in the differential diagnosis in ALF. Further studies would aid in determining the true impact of this infection in Argentina and the potential benefits of a vaccine against HEV, presently in phase III trials.(AU)

Infeccion por virus de hepatitis A (HAV) en ninos en Argentina: ensayo piloto / Hepatitis A virus infection in children in Argentina: a pilot study

Objetivos: Determinar la curva de infección del HAV en niños menores de diez años. Establecer estrategias de vacunación en la Argentina. Material y Métodos: se etableció un grupo cooperativo para el rastreo serológico de niños entre los seis meses y los diez años de edad, sin sintomatología y/o cuadro clínico de hepatitis aguda, tomando como grupo inicial de trabajo a Centros de las ciudades de Bs. As., San Justo (Pcia, de Bs. As.), Trelew (Chubut), Rosario (Santa Fe) y Tucumán. Se estudiaran 3699 niños para Anti-HAV-IgG por ELISA (Oragnon y Abbott). Las variables de inclusión fueron: edad, sexo y calidad de agua. Resultados: 45.19 por ciento de las muestras fueron de San Justo, 26.15 por ciento de Rosario, 13 por ciento de Buenos Aires, 7.29 por ciento de Tucumán y 8.37 por ciento de Trelew. 1) Se observó el mayor porcentaje de positividad (porcentajePOS) en Tucuman (81.4 por ciento) seguido por San Justo (57.8 por ciento) y Rosario (44.3 por ciento). 2) En todas las ciudades los menores porcentajePOS correspondieron a menores de tres años. 3) La mayor dispersión del porcentajePOS ocurre entre los tres y seis años de edad. 4) en todo el muestreo se observó un valor creciente de porcentajePOS con pendientes similares, excepto para Trelew, donde aparece un pico a los cuatro años atribuíble a las características de la muestra. 5) El porcentajePOS global para la muestra fue de 51.56 por ciento. Conclusiones: 1) Este trabajo demuestra que nuestro país es de alta endemicidad para la infección por HAV. 2) La vacunación a corta edad sería la estrategia más adecuada para el control de la hepatitis A y la erradicación de la infección por el HAV. (AU)

Infeccion por virus de hepatitis A (HAV) en ninos en Argentina: ensayo piloto / Hepatitis A virus infection in children in Argentina: a pilot study

Objetivos: Determinar la curva de infección del HAV en niños menores de diez años. Establecer estrategias de vacunación en la Argentina. Material y Métodos: se etableció un grupo cooperativo para el rastreo serológico de niños entre los seis meses y los diez años de edad, sin sintomatología y/o cuadro clínico de hepatitis aguda, tomando como grupo inicial de trabajo a Centros de las ciudades de Bs. As., San Justo (Pcia, de Bs. As.), Trelew (Chubut), Rosario (Santa Fe) y Tucumán. Se estudiaran 3699 niños para Anti-HAV-IgG por ELISA (Oragnon y Abbott). Las variables de inclusión fueron: edad, sexo y calidad de agua. Resultados: 45.19 por ciento de las muestras fueron de San Justo, 26.15 por ciento de Rosario, 13 por ciento de Buenos Aires, 7.29 por ciento de Tucumán y 8.37 por ciento de Trelew. 1) Se observó el mayor porcentaje de positividad (porcentajePOS) en Tucuman (81.4 por ciento) seguido por San Justo (57.8 por ciento) y Rosario (44.3 por ciento). 2) En todas las ciudades los menores porcentajePOS correspondieron a menores de tres años. 3) La mayor dispersión del porcentajePOS ocurre entre los tres y seis años de edad. 4) en todo el muestreo se observó un valor creciente de porcentajePOS con pendientes similares, excepto para Trelew, donde aparece un pico a los cuatro años atribuíble a las características de la muestra. 5) El porcentajePOS global para la muestra fue de 51.56 por ciento. Conclusiones: 1) Este trabajo demuestra que nuestro país es de alta endemicidad para la infección por HAV. 2) La vacunación a corta edad sería la estrategia más adecuada para el control de la hepatitis A y la erradicación de la infección por el HAV.