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Master of Public Health

Safety and Efficacy of a Typhoid Conjugate Vaccine in Malawian Children

AUTHORS

Patel PD , Patel P , Liang Y , Meiring JE , Misiri T , Mwakiseghile F , Tracy JK , Masesa C , Msuku H , Banda D , Mbewe M , Henrion M , Adetunji F , Simiyu K , Rotrosen E , Birkhold M , Nampota N , Nyirenda OM , Kotloff K , Gmeiner M , Dube Q , Kawalazira G , Laurens MB , Heyderman RS , Gordon MA , Neuzil KM , , . The New England journal of medicine. ; 385(12). 1104-1115

ABSTRACT

BACKGROUND: Typhoid fever caused by multidrug-resistant H58 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.).

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