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.
Center of Excellence in Clinical Virology, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Pattaratida
P
Sa-Nguanmoo
Pisit
P
Tangkijvanich
Piyanit
P
Tharmaphornpilas
Aim-Orn
AO
Rasdjarmrearnsook
Saowanee
S
Plianpanich
Nutchanart
N
Thawornsuk
Apiradee
A
Theamboonlers
Yong
Y
Poovorawan
D000328:Adult; D016022:Case-Control Studies; D004279:DNA, Viral / Q000032:analysis / Q000097:blood; D005260:Female; D005838:Genotype; D017325:Hepatitis B Vaccines / Q000008:administration & dosage / Q000627:therapeutic use*; D006513:Hepatitis B e Antigens / Q000097:blood / Q000235:genetics; D006515:Hepatitis B virus / Q000235:genetics* / Q000276:immunology; D019694:Hepatitis B, Chronic / Q000517:prevention & control* / Q000635:transmission* / Q000821:virology; D006801:Humans; D007223:Infant; D018445:Infectious Disease Transmission, Vertical; D009154:Mutation; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000517:prevention & control* / Q000821:virology; D013785:Thailand; D017211:Treatment Failure; D055815:Young Adult
D004279:DNA, Viral; D017325:Hepatitis B Vaccines; D006513:Hepatitis B e Antigens