Survey of hepatitis B surface variant infection in children 15 years after a nationwide vaccination programme in Taiwan

Background: It is not known whether hepatitis B virus (HBV) with mutations in the a determinant ( amino acids (aa) 121 - 149) of the hepatitis B surface antigen ( HBsAg) affect vaccination efficacy. Aim: To investigate the prevalence and clinical significance of these mutants in children, 15 years after universal vaccination in Taiwan. Methods: Nucleotide sequences encoding the a determinant region ( aa 110 - 160) of HBsAg were analysed in all HBV-DNA positive sera from 1357 children and 219 adolescents serosurveyed in 1999. We then compared the prevalence and changes in the mutants in these children with our previous surveys in the same area conducted in 1984 ( just before vaccination), 1989, and 1994. Results: The prevalence of a determinant mutants in HBV-DNA positive children was 7.8% (8/103) in 1984, which significantly increased to 19.6% (10/51) in 1989, peaked at 28.1% (9/32) in 1994, and remained at 23.1% ((3/13) (T131I, G145R, G145R)) in 1999; it was higher in those fully vaccinated compared with those not vaccinated (15/46 v 15/153; p< 0.001). However, the number of mutant infected children in each survey was stable in the first 5 - 10 year period but decreased 10 - 15 years post vaccination. Increased amino acid variation in the a determinant region occurred in carrier children in the post vaccination survey. Mutated residues tended to occur more frequently in the region with greater local hydrophilicity ( residues 140 - 149) in those vaccinated than in unvaccinated children with variant infection (12/15 v 6/15; p = 0.062). More HBsAg positive a determinant mutants emerged in children fully vaccinated with plasma derived vaccine than those given recombinant vaccine (10/2399 (0.46%) v 0/503; p = 0.122). Conclusion: We found that a determinant variants have an advantage in infecting immunised children but do not threaten current HBV vaccination strategies in Taiwan.