Safety and immunogenicity of Vi-typhoid conjugate vaccine co-administration with routine 9-month vaccination in Burkina Faso: A randomized controlled phase 2 trial

Sodiomon Bienvenu Sirima ,Marcela F Pasetti,Elizabeth T Rotrosen,Issa Nébié,Issiaka Soulama,Kathleen M Neuzil,Matthew B Laurens,Edith C Bougouma,Amidou Diarra,Nouhoun Barry,Yuanyuan Liang,Shrimati Datta,J Kathleen Tracy,Gloria Damoaliga Berges,Alphonse Ouédraogo ,Mohamadou Siribié ,Amadou T Konaté ,Jennifer Oshinsky ,Alfred B Tiono ,Alimatou Héma ,Moussa Ouédraogo ,Leslie P Jamka

doi:10.1016/j.ijid.2021.05.061

Abstract

ObjectivesIn 2017, the World Health Organisation (WHO) pre-qualified a single-dose typhoid conjugate vaccine (TCV) and identified TCV co-administration studies as a research priority. Accordingly, we tested co-administration of Typbar TCV® (Bharat Biotech International) with measles-rubella (MR) and yellow fever (YF) vaccines. MethodsWe conducted a randomized, double-blind, and controlled, phase 2 trial in Ouagadougou, Burkina Faso. Healthy children aged 9–11 months were randomized 1:1 to receive TCV (Group 1) or control vaccine (inactivated polio vaccine (IPV), Group 2). Vaccines were administered intramuscularly with routine MR and YF vaccines. Safety was assessed by (1) local and systemic reactions on days 0, 3, and 7; (2) unsolicited adverse events within 28 days; and (3) serious adverse events (SAEs) within six months after immunization. ResultsWe enrolled, randomized, and vaccinated 100 eligible children (49 Group 1 and 51 Group 2). Safety outcomes occurred with similar frequency in both groups: local/solicited reactions (Group 1: 1/49, Group 2: 3/50), systemic/solicited reactions (Group 1: 4/49, Group 2: 9/50), unsolicited adverse events (Group 1: 26/49, Group 2: 33/51), and SAEs (Group 1: 2/49, Group 2: 3/51). TCV conferred robust immunogenicity without interference with MR or YF vaccines. ConclusionTCV can be safely co-administered with MR and YF vaccines to children at the 9-month vaccination visit.

Highlights

Typhoid fever, a potentially life-threatening infection caused by the bacterium Salmonella enterica serovar Typhi
Double-blind, controlled, phase 2 trial, evaluating the safety and immunogenicity of typhoid conjugate vaccine (TCV) when co-administered with vaccinations routinely given at 9 months of age in Burkina Faso
The study was conducted by the Groupe de Recherche Action en Santé (GRAS) at Schiphra Protestant Hospital outpatient pediatric clinic, an urban hospital in Ouagadougou, Burkina Faso, December 2018 to August 2019

Summary

Introduction

A potentially life-threatening infection caused by the bacterium Salmonella enterica serovar Typhi Typhi), is spread through contaminated food and water. It is estimated that more than nine million cases of typhoid fever and more than 110,000 deaths occur worldwide each year (Institute for Health Metrics and Evaluation, 2020). Multidrug-resistant typhoid fever appeared in the 1970s and has spread globally, with 47% of S. Typhi isolates reported to be resistant to first-line agents (Marks et al, 2017; Wong et al, 2015). Typhoid fever incidence has traditionally been highest in school-age children (5–19 years), yet is increasingly recognized as a public health problem in children under five

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