• 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, and Kathleen M Neuzil.
• Oxford Vaccine Group, Department of Paediatrics, Oxford University, United Kingdom.
• Clin. Infect. Dis. 2019 Mar 7; 68 (Suppl 2): S50-S58.

BackgroundTyphoid 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.MethodsIn 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.ResultsAll 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.ConclusionsThe 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 RegistrationNCT03299426.© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America.

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