Co-circulation of genotype IA and new variant IB hepatitis A virus in outbreaks of acute hepatitis in Hungary—2003/2004

Hepatitis A virus (HAV) is one of the most important causes of acute infectious hepatitis worldwide. In Hungary, the reported number of HAV infections has been decreasing in the last four decades, nevertheless, still, each year 500-800 new cases and multiple outbreaks occur, particularly in the northeast region of Hungary. In Hungary, serology is used routinely to establish the diagnosis of HAV infection without genetic analysis of HAV strains for molecular epidemiology. In this study, serum samples collected from symptomatic patients were tested by enzyme-immunoassay (anti-HAV-IgM ELISA) to establish the cause of three acute hepatitis A outbreaks (outbreak 1--from low prevalence region in Southwest Hungary in 2003 and outbreaks 2 and 3 from the endemic region in Northeast Hungary in 2004). Outbreak strains were characterized by reverse transcription-polymerase chain reaction (RT-PCR) amplification of a 360 bp viral VP1/2A region, amplicon sequencing and phylogenetic analysis. Four, seven, and three sera from outbreaks 1, 2, and 3, respectively, were investigated by RT-PCR for HAV genome and HAV RNA was detected in 4 (100%), 4 (57%), and 2 (67%) samples. All strains belonged to genotype I HAV. Outbreak 1 was caused by the new variant subtype IB and outbreaks 2 and 3 caused by genetically identical subtype IA strains. The Hungarian IA and IB hepatitis A viruses had the highest nucleotide identity, 98.4% and 99.0%, to IT-SCH-00 and IT-MAR-02 strains, respectively, detected in year 2000 and 2002 in Italy. Endemic subtype IA and probably imported new variant subtype IB HAV viruses was detected in outbreaks of hepatitis in Hungary that are closely related genetically to HAV strains in Italy.