Real-world vaccine effectiveness of typhoid conjugate vaccine in children and adolescents: a systematic review and meta-analysis

Introduction: Typhoid fever, caused by Salmonella enterica serovar Typhi (S. Typhi), can be transmitted via faecal-oral route. Although significant reduction in incidence from 11 million in 2017 to 7 million in 2021, typhoid fever remains a global health problem. The World Health Organization (WHO) recommended implementation of typhoid conjugate vaccine (TCV) in endemic countries. However, only ten countries have introduced TCV into their national immunisation programs to date. This study aims to estimate the real-world effectiveness of TCV to inform evidence-based decision making and support implementation in typhoid-endemic countries. Method(s): In this systematic review and meta-analysis (SRMA), we searched MEDLINE (PubMed), EMBASE, Web of Science, and Cochrane Library. We included post-licensure observational and non-randomised studies evaluating vaccine effectiveness (VE) of TCV among children and adolescents published up to August 14th, 2025. Four TCV vaccines - Typbar TCV, TYPHIBEV, SKYTyphoidTM, and ZyVac TCV- had been WHO-prequalified at the time of review. The protocol is registered with PROSPERO (CRD42023456130). Result(s): We identified 1337 records and included four studies in the meta-analysis, comprising 24,180 individuals from three countries (Pakistan, India, and Zimbabwe) comparing single-dose Typbar TCV recipients with unvaccinated children. TCV prevented culture-confirmed typhoid with VE of 87 % (95 % CI, 57-94 %). TCV also prevented combined suspected, probable, and culture-confirmed typhoid with VE of 55 % (95 % CI, 0.52-57 %) and extensively drug-resistant (XDR) S. Typhi with VE of 97 % (95 % CI, 95-98 %). Sensitivity analysis (eight studies, five countries; see Supplementary File) indicated a higher VE among older children (above 5 years) and a significant decline in protection 4-5 years after vaccination. Conclusion(s): Typhoid conjugate vaccines (TCV) demonstrate significant real-world effectiveness in preventing culture-confirmed, probable, suspected, and extensively drug-resistant (XDR) typhoid cases in endemic regions. This systematic review and meta-analysis support the implementation of TCV into national immunisation programs in typhoid-endemic countries. Significance: No previously published systematic review and meta-analysis evaluate the effectiveness of TCV. Evidence on real-world effectiveness is needed to support typhoid endemic countries considering the introduction of TCV into their national immunisation program. Copyright © 2025