Protection by vaccination of children against typhoid fever with a Vi-tetanus toxoid conjugate vaccine in urban Bangladesh: a cluster-randomised trial

Lancet. 2021 Aug 21;398(10301):675-684. doi: 10.1016/S0140-6736(21)01124-7. Epub 2021 Aug 9.


Background: Typhoid fever remains a major cause of morbidity and mortality in low-income and middle-income countries. Vi-tetanus toxoid conjugate vaccine (Vi-TT) is recommended by WHO for implementation in high-burden countries, but there is little evidence about its ability to protect against clinical typhoid in such settings.

Methods: We did a participant-masked and observer-masked cluster-randomised trial preceded by a safety pilot phase in an urban endemic setting in Dhaka, Bangladesh. 150 clusters, each with approximately 1350 residents, were randomly assigned (1:1) to either Vi-TT or SA 14-14-2 Japanese encephalitis (JE) vaccine. Children aged 9 months to less than 16 years were invited via parent or guardian to receive a single, parenteral dose of vaccine according to their cluster of residence. The study population was followed for an average of 17·1 months. Total and overall protection by Vi-TT against blood culture-confirmed typhoid were the primary endpoints assessed in the intention-to-treat population of vaccinees or all residents in the clusters. A subset of approximately 4800 participants was assessed with active surveillance for adverse events. The trial is registered at, ISRCTN11643110.

Findings: 41 344 children were vaccinated in April-May, 2018, with another 20 412 children vaccinated at catch-up vaccination campaigns between September and December, 2018, and April and May, 2019. The incidence of typhoid fever (cases per 100 000 person-years) was 635 in JE vaccinees and 96 in Vi-TT vaccinees (total Vi-TT protection 85%; 97·5% CI 76 to 91, p<0·0001). Total vaccine protection was consistent in different age groups, including children vaccinated at ages under 2 years (81%; 95% CI 39 to 94, p=0·0052). The incidence was 213 among all residents in the JE clusters and 93 in the Vi-TT clusters (overall Vi-TT protection 57%; 97·5% CI 43 to 68, p<0·0001). We did not observe significant indirect vaccine protection by Vi-TT (19%; 95% CI -12 to 41, p=0·20). The vaccines were well tolerated, and no serious adverse events judged to be vaccine-related were observed.

Interpretation: Vi-TT provided protection against typhoid fever to children vaccinated between 9 months and less than 16 years. Longer-term follow-up will be needed to assess the duration of protection and the need for booster doses.

Funding: The study was funded by the Bill & Melinda Gates Foundation.

Publication types

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

MeSH terms

  • Adolescent
  • Bangladesh / epidemiology
  • Child
  • Child, Preschool
  • Developing Countries
  • Encephalitis, Japanese / epidemiology
  • Female
  • Humans
  • Infant
  • Japanese Encephalitis Vaccines / administration & dosage
  • Male
  • Polysaccharides, Bacterial / administration & dosage*
  • Salmonella typhi / immunology
  • Tetanus Toxoid / immunology
  • Tetanus Toxoid / therapeutic use*
  • Typhoid Fever / epidemiology
  • Typhoid Fever / immunology
  • Typhoid Fever / prevention & control*
  • Typhoid-Paratyphoid Vaccines / administration & dosage*
  • Vaccination*
  • Vaccines, Conjugate / administration & dosage*


  • Japanese Encephalitis Vaccines
  • Polysaccharides, Bacterial
  • Tetanus Toxoid
  • Typhoid-Paratyphoid Vaccines
  • Vaccines, Conjugate
  • Vi polysaccharide vaccine, typhoid