Safety and Efficacy of a Typhoid Conjugate Vaccine in Malawian Children

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

BACKGROUND: Typhoid fever caused by multidrug-resistant H58 Salmonella Typhi is an increasing public-health threat in sub-Saharan Africa. We present phase 3 efficacy data from an African trial of a Vi-polysaccharide typhoid conjugate vaccine (Vi-TCV). METHODS: Children aged 9 months to 12 years in Blantyre, Malawi were randomized (1:1) in a double-blind trial to receive Vi-TCV (single dose) or group-A meningococcal control vaccine (MenA).The primary outcome was blood culture-confirmed typhoid fever. We present the primary vaccine efficacy (VE) and safety outcomes after 18–24 months of follow-up. RESULTS: This intention-to-treat (ITT) analysis included 28,130 children, comprising 14,069 children who received Vi-TCV and 14,061 children who received MenA. Blood culture-confirmed typhoid fever occurred in 12 children in the Vi-TCV group (46.9 per 100,000 person-years) and 62 children in the MenA group (243 per 100,000 person-years). Overall VE was 80.7% (95% confidence interval (CI): 64.2% to 89.6%) in an ITT analysis, and 83.7% (95% CI: 68.1%−91.6%) in a per-protocol analysis. In total, 130 serious adverse events occurred in the first 6 months after vaccination (52 in Vi-TCV group and 78 in MenA group), including 6 deaths (all in MenA group). No serious adverse event was considered by the investigator as related to study vaccination. CONCLUSIONS: Vi-TCV reduced blood culture-confirmed typhoid fever among Malawian children aged 9 months to 12 years. (Funded by the Bill & Melinda Gates Foundation; ClinicalTrials.gov number NCT03299426.)