Typhoid vaccine acceleration consortium Malawi: A Phase III, randomized, double-blind, controlled trial of the clinical efficacy of typhoid conjugate vaccine among children in Blantyre, Malawi

James E. Meiring, Matthew B. Laurens, Pratiksha Patel, Priyanka Patel, Theresa Misiri, Kenneth Simiyu, Felistas Mwakiseghile, J. Kathleen Tracy, Clemens Masesa, Yuanyuan Liang, Marc Henrion, Elizabeth Rotrosen, Markus Gmeiner, Robert Heyderman, Karen Kotloff, Melita A. Gordon, Kathleen M. Neuzil

Research output: Contribution to journalArticle

Abstract

Background Typhoid fever is an acute infection characterized by prolonged fever following the ingestion and subsequent invasion of Salmonella enterica serovar Typhi (S. Typhi), a human-restricted pathogen. The incidence of typhoid fever has been most reported in children 5-15 years of age, but is increasingly recognized in children younger than 5 years old. There has been a recent expansion of multidrug-resistant typhoid fever globally. Prior typhoid vaccines were not suitable for use in the youngest children in countries with a high burden of disease. This study aims to determine the efficacy of a typhoid conjugate vaccine (TCV) that was recently prequalified by the World Health Organization, by testing it in children 9 months through 12 years of age in Blantyre, Malawi. Methods In this Phase III, individually randomized, controlled, double-blind trial of the clinical efficacy of TCV, 28 000 children 9 months through 12 years of age will be enrolled and randomized in a 1:1 ratio to receive either Vi-TCV or a meningococcal serogroup A conjugate vaccine. A subset of 600 of these children will be further enrolled in an immunogenicity and reactogenicity sub-study to evaluate the safety profile and immune response elicited by Vi-TCV. Recruiting began in February 2018. Results All children will be under passive surveillance for at least 2 years to determine the primary outcome, which is blood culture-confirmed S. Typhi illness. Children enrolled in the immunogenicity and reactogenicity sub-study will have blood drawn before vaccination and at 2 timepoints after vaccination to measure their immune response to vaccination. They will also be followed actively for adverse events and serious adverse events. Conclusions The introduction of a single-dose, efficacious typhoid vaccine into countries with high burden of disease or significant antimicrobial resistance could have a dramatic impact, protecting children from infection and reducing antimicrobial usage and associated health inequity in the world's poorest places. This trial, the first of a TCV in Africa, seeks to demonstrate the impact and programmatic use of TCVs within an endemic setting. Clinical Trials Registration NCT03299426.

Original languageEnglish (US)
Pages (from-to)S50-S58
JournalClinical Infectious Diseases
Volume68
DOIs
StatePublished - Mar 7 2019
Externally publishedYes

Keywords

  • Africa
  • children/pediatric
  • Malawi
  • typhoid conjugate vaccine
  • TyVAC

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases

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    Meiring, J. E., Laurens, M. B., Patel, P., Patel, P., Misiri, T., Simiyu, K., Mwakiseghile, F., Tracy, J. K., Masesa, C., Liang, Y., Henrion, M., Rotrosen, E., Gmeiner, M., Heyderman, R., Kotloff, K., Gordon, M. A., & Neuzil, K. M. (2019). Typhoid vaccine acceleration consortium Malawi: A Phase III, randomized, double-blind, controlled trial of the clinical efficacy of typhoid conjugate vaccine among children in Blantyre, Malawi. Clinical Infectious Diseases, 68, S50-S58. https://doi.org/10.1093/cid/ciy1103