Safety and Efficacy of a Typhoid Conjugate Vaccine in Malawian Children

N Engl J Med. 2021 Sep 16;385(12):1104-1115. doi: 10.1056/NEJMoa2035916.

Abstract

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.).

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Child
  • Child, Preschool
  • Double-Blind Method
  • Female
  • Follow-Up Studies
  • Humans
  • Incidence
  • Infant
  • Intention to Treat Analysis
  • Malawi
  • Male
  • Meningococcal Vaccines / adverse effects
  • Polysaccharides, Bacterial* / adverse effects
  • Salmonella typhi
  • Typhoid Fever / epidemiology
  • Typhoid Fever / prevention & control*
  • Typhoid-Paratyphoid Vaccines* / adverse effects
  • Vaccines, Conjugate

Substances

  • Meningococcal Vaccines
  • Polysaccharides, Bacterial
  • Typhoid-Paratyphoid Vaccines
  • Vaccines, Conjugate
  • Vi polysaccharide vaccine, typhoid

Associated data

  • ClinicalTrials.gov/NCT03299426