Molecular epidemiology of hepatitis A, B and C in Estonia

Abstract: During the last decade changes have occurred in the epidemiology of hepatitis A, B and C in Estonia. A shift from high to intermediate endemicity for HAV has led to a shift in age of susceptible individuals from children to adolescents and adults. A dramatic increase in injecting drug use in the population aged 15-29 years in the 90s has led to an increased incidence for both hepatitis B and C. Since genetic data on HAV, HBV and HCV strains are limited in Estonia, our aim was to characterize Estonian strains of these viruses and determine their relatedness to strains from other parts of the world. In 1998-1999 a small group of intravenous drug users became the source for a community-wide outbreak of hepatitis A in Estonia. 107 anti-lgM HAV positive sera sampled in Tallinn and Kohtla-Järve from hospitalised patients during the outbreak in 1998-1999 and 68 sera collected before and after the outbreak were used as source of HAV RNA for characterization of the viral VP1 region. All strains from 1998-1999 belonged to subtype IIIA, a subtype previously linked to addicts in Sweden during 1980s and in Norway in the 1990s while background strains belonged to subtype IA. The IA strains formed two discrete clades distinct from hepatitis A strains from other parts of the world. To characterize HBV 530 HBsAg positive sera collected during 1989-2002 in Estonia and 14 other regions of the former USSR were investigated. By sequencing the S-gene, three genotypes A (18.5%), D (81 %) and C (0.5%) were identified. The genotype D strains encoded ayw3, ayw2, ayw4 and adw3 subtypes. All genotype A strains encoded adw2 specificity and the genotype C strain adr. All isolates belonging to genotype A were found in the A2 subgenotype with mainly WestEuropean strains. 93% of the Estonian genotype D strains were more similar to isolates from Siberia and the Far-East of the former USSR, with higher similarity with Indian and Japanese strains, than with strains from Central Russia. To study HCV 352 anti-HCV positive sera collected during 1996-2004 from health care workers, blood donors and hospitalized patients were analysed. The subtypes of the strains were determined by phylogenetic analysis within the NS5B region. Subtype 1b was the most prevalent (71 %) followed by 3a (24%), 2c (2%), 1a (1 %) and 2a (1 %). One patient was infected with the 2k/1b recombinant previously found in St.Petersburg as determined by sequencing also the 5′ UTR-core regions. This is the first isolate of this recombinant recovered outside Russia. Relative changes in distribution of subtypes 1b and 3a was observed during the study period. Estonian lb strains were similar to strains published from different regions of the former USSR. In contrast the 3a strain seemed to be indigenous. More than one lineage of HCV could be recognized circulating in Estonia within these subtypes. In conclusion: Despite subtype IA of HAV has been dominating in Estonia during 1994-2001, the outbreak in 1998-1999 was due to subtype IIIA. This study provides further framework for the use of VP l sequencing for molecular epidemiology of hepatitis A. The in Europe prevailing HBV genotypes, A and D, were also circulating in the territory of the former USSR including Estonia. Strains from Estonia were more similar to strains from Siberia than to strains from Central Russia. The most prevalent HCV subtypes in Estonia were lb and 3a. A shift from lb to 3a partially coinciding with the hepatitis A outbreak in IDUs with further replacement of 3a with lb was shown. Both genotypes seemed to co-circulate in the community independent from risk factors.