IJID regions · 2026
Genomic characterization of hepatitis B virus from a vaccinated child in Nigeria suggests delayed neonatal immunoprophylaxis rather than vaccine escape: a case report.
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Akomolafe Busayo Kayode, Akomolafe Etuvie Favour, Animasaun Olawale Sunday, Fasanmi Bamidele Temidayo, Danladi Nengak Precious, Audu Rosemary Ajuma
Аннотация
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.
OBJECTIVES: This case report describes the molecular characterization of HBV isolated from a vaccinated Nigerian child with breakthrough hepatitis B surface antigen (HBsAg) positivity, with particular emphasis on viral genotype, HBsAg variation, recognized vaccine-escape mutations and antiviral resistance-associated mutations.
METHODS: Children participating in a hepatitis B vaccine impact study in Oyo State, Nigeria, were screened for HBsAg. Positive samples underwent quantitative polymerase chain reaction, whole-genome amplification and Oxford Nanopore sequencing. Consensus genomes were analyzed 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 deoxyribonucleic acid, but only one yielded sufficient viral load for complete genome sequencing. Phylogenetic analysis classified the isolate as genotype E. No recognized 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.
OBJECTIVES: This case report describes the molecular characterization of HBV isolated from a vaccinated Nigerian child with breakthrough hepatitis B surface antigen (HBsAg) positivity, with particular emphasis on viral genotype, HBsAg variation, recognized vaccine-escape mutations and antiviral resistance-associated mutations.
METHODS: Children participating in a hepatitis B vaccine impact study in Oyo State, Nigeria, were screened for HBsAg. Positive samples underwent quantitative polymerase chain reaction, whole-genome amplification and Oxford Nanopore sequencing. Consensus genomes were analyzed 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 deoxyribonucleic acid, but only one yielded sufficient viral load for complete genome sequencing. Phylogenetic analysis classified the isolate as genotype E. No recognized 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.