Molecular epidemiology of hepatitis A in the Netherlands

by Tjon, Grace Marjorie

A viral sequencing study was performed on samples representing all reported primary cases of acute hepatitis A virus (HAV) infection reported over two years in Amsterdam. Two regions of HAV RNA were amplified and sequenced and used for phylogenetic analysis. Of 156 cases, strains of 104 isolates (66%) clustered into three genotypes: 1A, 1B and 3. Two separate transmission circles occurred, without mutual interrelation. In genotype 1A, four clusters were related to men having sex with men, the fifth related to a virus imported from Morocco. In genotype 1B, six small clusters were directly related to the Moroccan import. In genotype 3, import cases were related to Pakistan. Our analysis indicates that, to stop HAV transmission in Amsterdam, the entire homosexual population should be vaccinated, as well as travellers to HAV-endemic countries, especially children. Prevention strategies need not to include vaccination of all children living in Amsterdam. Molecular epidemiology of HAV in Amsterdam ?21 Introduction In most of the world hepatitis A virus (HAV) infection is known as an innocent, often asymptomatic childhood disease. In the rich industrialized world, however, with decreased crowding and increased hygiene and public health interventions, HAV infection occurs at a later age, with increased morbidity and mortality over the age of 40 years1,2. In the Netherlands, where symptomatic HAV cases are notifiable, the incidence of reported cases has varied in the last decade from 4.1 to 7.9/100,0003. The incidence of reported cases in Amsterdam was 23.1/100,000 from 1991-2000, with lower incidence in the last four years4,5. Amsterdam is assumed to have approximately 735,000 inhabitants, of whom 37% originate from developing countries where HAV is endemic. Enhanced surveillance, in the four largest cities of the country, suggests that children of this subpopulation import HAV on return from travel to the country of origin, causing secondary transmission within their family, schools or daycare centers6. Susceptible household members of notified cases are immunized with immunoglobulin. If a cluster of cases points to transmission in a school or daycare center, immunoglobulin is administered to susceptible group- or classmates and sometimes to their relatives. We started annual hepatitis A vaccination programs in 1998, for children visiting their country of parental origin, but achieved vaccination coverage of less than 50% for children under 16 years of age7. Also, school-related clusters continued to occur4,5. Since vaccine costs seem to argue against universal childhood vaccination in the Netherlands8, we sought a targeted approach, by investigating the molecular epidemiology of HAV in Amsterdam. We isolated and sequenced