Mother to Infant Transmission of Hepatitis B Virus in the Face of Neonatal Immunization Is Not Necessarily Primary Vaccine Failure

Abstract

Surveillance programmes undertaken in infants born to hepatitis B virus (HBV) infected mothers provide an opportunity to analyse virological markers from the neonate and early infancy. These data inform on mechanisms of HBV transmission and how available interventions can be better utilised for control of HBV infections arising at the mother/child interface. Retrospective analysis of HBV serological markers was undertaken in Dried Blood Spots collected from infants born to HBV-infected mothers. In addition, molecular analysis was performed in newborn blood spot cards, collected after birth, from infants identified as HBV-infected despite receiving prophylaxis. Perinatal exposure could not account for all transmissions with at least one quarter (22%) of infants already infected in utero. All harboured a wild type HBsAg, with identical sequences noted in the neonatal and early infancy samples. In contrast, in infants infected perinatally (43%), selection of viruses harbouring amino acid changes in the HBsAg were common (80% of sequences) and divergent from the linked maternal sample. Currently considered to represent vaccine failure, it is likely that a proportion of HBV infections result from in utero acquisition. These infections are unlikely to be susceptible to post-natal prophylaxis and current recommendations for maternal antiviral treatment may be too late to prevent transmission. Consideration should be given to the earlier use of antivirals during gestation to reduce the risk of intrauterine transmission together with completion of the immunisation schedule also to reduce the perinatal risk of HBV transmission.