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Safety and Efficacy of a Typhoid Conjugate Vaccine in Malawian Children

2021; Massachusetts Medical Society; Volume: 385; Issue: 12 Linguagem: Inglês

10.1056/nejmoa2035916

1533-4406

Priyanka Patel, Pratiksha Patel, Yuanyuan Liang, James Meiring, Theresa Misiri, Felistas Mwakiseghile, J. Kathleen Tracy, Clemens Masesa, Harrison Msuku, David Banda, Maurice Mbewe, Marc Henrion, Fiyinfolu Adetunji, Kenneth Simiyu, Elizabeth Rotrosen, Megan Birkhold, Nginache Nampota-Nkomba, Osward M. Nyirenda, Karen L. Kotloff, Markus Gmeiner, Queen Dube, Gift Kawalazira, Matthew B. Laurens, Robert S. Heyderman, Melita A. Gordon, Kathleen M. Neuzil,

Clostridium difficile and Clostridium perfringens research

Typhoid fever caused by multidrug-resistant H58 Salmonella Typhi is an increasing public health threat in sub-Saharan Africa.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.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.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.).