article · IJID Regions
Breakthrough hepatitis B infections in vaccinated children are often blamed on viral escape mutations, but delayed neonatal immunisation and mother-to-child transmission are also critical factors. In a study conducted in Oyo State, Nigeria, 336 vaccinated children were screened for hepatitis B surface antigen, revealing four positive cases. Genomic analysis using Oxford Nanopore sequencing was performed on the single sample with a sufficient viral load, classifying the virus as genotype E. Crucially, the viral genome revealed no recognised vaccine escape mutations or antiviral resistance markers. An examination of immunisation records showed that the infant received their first vaccine dose at two weeks of age rather than at birth. This two-week delay in neonatal immunisation offers a plausible explanation for the breakthrough infection, underscoring the vital importance of timely birth-dose delivery over viral mutation concerns.
Distinguishing between vaccine failure caused by viral mutations and failure caused by delayed administration is essential for public health. This work demonstrates that breakthrough hepatitis B infections can occur simply due to postponed neonatal immunisation rather than ineffective vaccines, reinforcing the necessity for prompt delivery of birth doses to prevent transmission in endemic regions.
The abstract does not indicate an application pathway, as it is an observational case report evaluating clinical immunisation timing and viral genomics rather than a commercial product or service.
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Background Breakthrough hepatitis B virus (HBV) infections continue to be reported among vaccinated children in endemic settings. Although viral escape mutations are often suspected, delayed neonatal immunoprophylaxis and vertical transmission remain important but under-investigated mechanisms. Whole-genome sequencing provides an opportunity to distinguish between these competing explanations and strengthen molecular surveillance. Aims and Objectives This case report describes the molecular characterization of HBV isolated from a vaccinated Nigerian child with breakthrough HBsAg positivity, with particular emphasis on viral genotype, HBsAg variation, recognized vaccine-escape mutations and antiviral resistance-associated mutations. Methodology Children participating in a hepatitis B vaccine impact study in Oyo State, Nigeria, were screened for HBsAg. Positive samples underwent quantitative PCR, whole-genome amplification and Oxford Nanopore sequencing. Consensus genomes were analysed using phylogenetic and mutation analyses to determine genotype, vaccine escape mutations and antiviral resistance profiles. Results Among 336 vaccinated children, four were HBsAg positive (1.2%). Two samples had detectable HBV DNA, but only one yielded sufficient viral load for complete genome sequencing. Phylogenetic analysis classified the isolate as genotype E. No recognised vaccine escape mutations or antiviral resistance-associated mutations were detected. Review of immunization records showed that the child received the first hepatitis B vaccine dose at 2 weeks of age and subsequently completed the vaccination schedule. This approximately 14-day delay in birth-dose vaccination provides a plausible explanation for the breakthrough infection in the absence of recognized vaccine-escape mutations. Conclusion Whole-genome sequencing demonstrated that HBV infection in this vaccinated child was unlikely to have resulted from recognized vaccine-escape mutations. Instead, delayed birth-dose vaccination provides a more plausible explanation for the breakthrough infection, although perinatal transmission could not be confirmed because maternal HBV status was unavailable.
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DOI: 10.1016/j.ijregi.2026.101003
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