Molecular analysis of hepatitis B virus associated with vaccine failure in infants and mothers: a case-control study in Thailand.

Perinatal transmission of hepatitis B virus (HBV) has been controlled incompletely despite adequate immunoprophylaxis in infants. The aim of this study was to characterize virological factors of HBV associated with vaccine failure in Thailand. Sera of 14 infected infants (13 HBeAg-positive and one HBeAg-negative) with vaccine failure and their respective mothers (group M1) were tested quantitatively for HBV DNA by real-time PCR, HBV genotypes and mutations were characterized by direct sequencing. Sera collected from 15 HBeAg-positive (group M2) and 15 HBeAg-negative (group M3) mothers whose infants had been vaccinated successfully served as controls. The results showed that group M1 and group M2 mothers had equal titers of HBV DNA but higher titers than group M3. All infected infants and their respective mothers had the same HBeAg status and HBV genotypes. DNA analysis in a pair of HBeAg-negative infant and mother revealed that both were infected with an HBV precore mutant (G1896A). Escape mutants in the "a" determinant region (residues 144 and 145) were detected in two (14%) infected infants. The prevalence of BCP mutations/deletions in groups M2 and M3 was higher significantly than in group M1 (P = 0.022 and P < 0.001, respectively). In conclusion, instead of the HBeAg status, a high titer of HBV DNA in mothers was the major contributor to perinatal transmission of HBV. Escape mutants might be associated with vaccine failure in some infants. BCP mutations/deletions in mothers might contribute to the prevention of mother-to-infant transmission of HBV.

Increased risk of developing chronic HBV infection in infants born to chronically HBV infected mothers as a result of delayed second dose of hepatitis B vaccination.

This two-stage study (cross-sectional and case-control) assessed the effects of delayed second dose HB vaccination on the risk of developing chronic HBV infection in infants born to chronically HBV infected mothers. 521 infants enrolled received the first vaccination by the end of the day after birth, without HBIG. 15 of these infants were chronically HBV infected. In the case-control comparison, controlling for HBeAg in the mother, the risk of an infant becoming chronically infected was 3.74 times (95% CI=0.97-14.39) higher if the interval between the first and the second doses exceeded 10 weeks. This finding suggests it is important that immunization programs ensure timely second dose vaccination to infants born to mothers with chronic HBV infection. Nevertheless, due to the small sample size, these findings should be verified by larger studies.

Seroprevalence of antibodies to measles, mumps, and rubella among Thai population: evaluation of measles/MMR immunization programme.

Stored serum specimens, from four regions of Thailand, of healthy children attending well baby clinics and of healthy people with acute illnesses visiting outpatient clinics were randomly sampled and tested for IgG antibody to measles, mumps, and rubella (MMR). The immunity patterns of rubella and mumps fitted well with the history of rubella and MMR vaccination, seroprotective rates being over 85% among those aged over seven years. A high proportion of younger children acquired the infection before the age of vaccination. MMR vaccination should preferably be given to children at an earlier age. For measles, 73% seroprotective rates among children, aged 8-14 years, who should have received two doses of measles/MMR vaccine, were lower than expected. This finding was consistent with the age-group reported in outbreaks of measles in Thailand. The apparent ineffectiveness (in relation to measles) of MMR immunization of 1st grade students warrants further studies.