BackgroundSalmonella Typhi is a major cause of fever in children in low- and
middle-income countries. The recently WHO prequalified typhoid conjugate vaccine (TCV)
was shown to be efficacious in a human challenge model but no efficacy trials in endemic
populations have been completed.MethodsIn this phase III participant- and observer-blinded randomized controlled trial in
Lalitpur, Nepal, children aged 9 months to <16 years of age, were randomized 1:1
to receive either TCV or a capsular group A meningococcal conjugate vaccine (Men A) as
control. The primary endpoint was blood culture-confirmed typhoid fever. Study follow-up
continues for 2 years; here we present the interim analysis after 12 months of
follow-up, for safety, immunogenicity and efficacy.Results10,005 participants received TCV and 10,014 received Men A. Blood culture-confirmed
typhoid fever occurred in 7 participants who received TCV and 38 receiving Men A;
vaccine efficacy: 81.6% (95% CI, 58.8%, 91.8%, P<0.001). 132 SAEs occurred in the
first 6 months with one (pyrexia) identified as vaccine-related. The participant remains
blinded. Seroconversion (≥ four-fold rise in Vi-IgG 28 days after vaccination)
was 99% in the TCV group (N=677/683) and 2% in the control group (N=8/380).ConclusionA single dose of TCV is safe, immunogenic, and effective, and the deployment of the
vaccine will reduce the burden of typhoid in high-risk populations. This new evidence of
efficacy is especially timely with the recent spread of extensively drug resistant
typhoid fever which threatens child health in affected regions.Trial registration numberISRCTN43385161