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. (7th March 2019)

• Record Type: Journal Article
• Authors: Meiring, James E; Laurens, Matthew B; Patel, Pratiksha; Patel, Priyanka; Misiri, Theresa; Simiyu, Kenneth; Mwakiseghile, Felistas; Tracy, J Kathleen; Masesa, Clemens; Liang, Yuanyuan; Henrion, Marc; Rotrosen, Elizabeth; Gmeiner, Markus; Heyderman, Robert; Kotloff, Karen; Gordon, Melita A; Neuzil, Kathleen M
• Is Part Of: Clinical infectious diseases. Volume 68(2019)Supplement 2
• Page Start: S50
• Page End: S58
• Publication Date: 2019-03-07
• Subjects: typhoid conjugate vaccine -- Malawi -- Africa -- children/pediatric -- TyVAC; Communicable diseases -- Periodicals; 616.905
• DOI: 10.1093/cid/ciy1103
• Languages: English
• ISSNs: 1058-4838

Abstract

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.