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.

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.

• Authors: 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
• Journal: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America (Clin Infect Dis) Vol. 68 Issue Suppl 2 Pg. S50-S58 (03 07 2019) ISSN: 1537-6591 [Electronic] United States
• PMID: 30845320 (Publication Type: Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America.

Chemical References

• Typhoid-Paratyphoid Vaccines
• Vaccines, Conjugate

Topics

• Child
• Child, Preschool
• Double-Blind Method
• Female
• Humans
• Immunogenicity, Vaccine
• Incidence
• Infant
• Malawi
• Male
• Salmonella typhi
• Treatment Outcome
• Typhoid Fever (prevention & control)
• Typhoid-Paratyphoid Vaccines (administration & dosage, immunology)
• Vaccination
• Vaccines, Conjugate (administration & dosage, immunology)
• World Health Organization