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Safety and Efficacy of a Typhoid Conjugate Vaccine in Malawian Children
Priyanka D Patel1, Pratiksha Patel1, Yuanyuan Liang1
1From the Malawi-Liverpool-Wellcome Program (P.D.P., P.P., J.E.M., T.M., F.M., C.M., H.M., D.B., M.M., M.H., M.G., M.A.G.), the Blantyre Malaria Project (N.N., O.M.N.), the Department of Paediatrics, Queen Elizabeth Central Hospital (Q.D.), the District Health Office, Blantyre District Council (G.K.), and Kamuzu University of Health Sciences (M.A.G.) - all in Blantyre, Malawi; the Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore (Y.L., J.K.T., F.A., K.S., E.R., M.B., K.K., M.B.L., K.M.N.); and Oxford Vaccine Group, the Department of Paediatrics, Oxford University, Oxford (J.E.M.), Liverpool School of Tropical Medicine (C.M., M.H., M.G.), and the Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool (M.A.G.), and the Division of Infection and Immunity, University College London, London (R.S.H.) - all in the United Kingdom.
Background:
Typhoid fever caused by multidrug-resistant H58 Salmonella Typhi is an increasing public health threat in sub-Saharan Africa.
Methods:
We conducted a phase 3, double-blind trial in Blantyre, Malawi, to assess the efficacy of Vi polysaccharide typhoid conjugate vaccine (Vi-TCV). We randomly assigned children who were between 9 months and 12 years of age, in a 1:1 ratio, to receive a single dose of Vi-TCV or meningococcal capsular group A conjugate (MenA) vaccine. The primary outcome was typhoid fever confirmed by blood culture. We report vaccine efficacy and safety outcomes after 18 to 24 months of follow-up.
Results:
The intention-to-treat analysis included 28,130 children, of whom 14,069 were assigned to receive Vi-TCV and 14,061 were assigned to receive the MenA vaccine. Blood culture-confirmed typhoid fever occurred in 12 children in the Vi-TCV group (46.9 cases per 100,000 person-years) and in 62 children in the MenA group (243.2 cases per 100,000 person-years). Overall, the efficacy of Vi-TCV was 80.7% (95% confidence interval [CI], 64.2 to 89.6) in the intention-to-treat analysis and 83.7% (95% CI, 68.1 to 91.6) in the per-protocol analysis. In total, 130 serious adverse events occurred in the first 6 months after vaccination (52 in the Vi-TCV group and 78 in the MenA group), including 6 deaths (all in the MenA group). No serious adverse events were considered by the investigators to be related to vaccination.
Conclusions:
Among Malawian children 9 months to 12 years of age, administration of Vi-TCV resulted in a lower incidence of blood culture-confirmed typhoid fever than the MenA vaccine. (Funded by the Bill and Melinda Gates Foundation; ClinicalTrials.gov number, NCT03299426.).
