Molecular epidemiology and variation of hepatitis B in recent immigrant families to Australia.

Natural variation in hepatitis B virus (HBV) was studied in asymptomatic carriers originating from countries of high endemicity. HBV DNA was detected by dot blot and/or polymerase chain reaction (PCR) in 34 of the 184 members of 22 new immigrant families who agreed to be tested after one of their children had been found to have current or past hepatitis B in a school survey. PCR products from both the S and distal-X pre-C regions were sequenced. One vaccinated child had the classical "escape" mutation at amino acid position 126 in the S-gene and two other children and two adults had other substitutions at amino acid positions 133, 120, 165, and 159. Mutations were more frequent in the distal-X pre-C region and included two pre-C mutants and 13 other amino acid substitutions. The strains originating in the various countries were placed in almost identical groups by phylogenetic analysis using each amplicon, and determination of subtype by antigenic analysis gave the same result as sequencing. The S-data allowed recognition of three dominant strains within genotype B, while the distal-X pre-C data provided better discrimination between family groups. No change was found when the sequence of samples obtained for the study was compared with those collected from 14 of the children two years earlier. There was some evidence of horizontal spread in addition to vertical transmission. Reports of mutations of HBV in patients with severe or unusual clinical features should be interpreted with caution until the prevalence of the mutant in asymptomatic carriers has been determined.