THE PREVALENCE OF SURFACE-ANTIGEN VARIANTS OF HEPATITIS-B VIRUS IN PAPUA-NEW-GUINEA, SOUTH-AFRICA, AND SARDINIA

Three assays, one based on monoclonal antibodies and the others on pol yclonal antibodies, were employed to detect hepatitis B surface antige n (HBsAg)-reactive samples in both vaccinated and unvaccinated populat ions in areas of the world where hepatitis B virus (HBV) is endemic. A ny discordant sera were tested by polymerase chain reaction (PCR) to c onfirm current infection, and sequence data were obtained from the DNA coding for the major hydrophilic region (MHR) of HBsAg of those sampl es positive for PCR. In all countries studied, samples that reacted in one HBsAg assay but not another were found. In the most extreme case, about 5% of viremic sera in Papua New Guinea were nonreactive in the monoclonal HBsAg assay; 9 of the 13 PCR-positive samples had novel or once-described variants, or a variant out of its usual genotype contex t. In South Africa, samples with sequences of subtype ayw2 reacted poo rly, particularly in the polyclonal assay. Two had novel variants. In Sardinia, antibody to hepatitis B core antigen (anti-HBc) was analyzed as a marker of infection. A significant proportion of anti-HBc-positi ve, but monoclonal HBsAg-negative, vaccinees and unvaccinated persons were found to be PCR positive, as were some individuals without any ma rkers of hepatitis B virus infection. Five more novel variants were fo und in these groups. There are implications for the design of HBsAg as says, which may have to be modified according to local sequence variab ility. Not all discordant samples were explained by variants, indicati ng that assay sensitivity is fundamental to diagnostic efficacy. Overa ll, this study defined 16 novel variants and 2 new potential epitope c lusters.