Typhoid Conjugate Vaccine Introduction in Madagascar (TyMA): Evaluation of the Real-World Effectiveness of the Vi-CRM197 Typhoid Conjugate Vaccine in Madagascar

This study evaluates the real-world effectiveness, safety, and immunogenicity of a single dose of the Vi-CRM197 typhoid conjugate vaccine (TCV) delivered through a mass vaccination campaign in selected districts of Madagascar. The study targets individuals aged 9 months to 45 years living in defined catchment areas with a high burden of typhoid fever. The project integrates three components: a population census with geographic mapping, a vaccination campaign using a WHO-prequalified Vi-CRM197 TCV, and prospective surveillance for typhoid fever. Vaccine effectiveness will be assessed by comparing the incidence of blood culture-confirmed Salmonella Typhi infection among vaccinated and unvaccinated individuals during follow-up. Additional outcomes include clinically suspected typhoid fever, severe disease, vaccine safety, immunogenicity, antibiotic use and consumption, and carriage of antimicrobial resistance (AMR) markers. The study aims to generate real-world evidence to inform public health decision-making regarding typhoid vaccine introduction and its broader impact on disease burden and antimicrobial resistance in endemic settings.

Inclusion Criteria: * Age 9 months to 45 years at the time of vaccination * Resident of the defined study catchment area in Madagascar * Parent(s), legal guardian, or participant (if adult) able and willing to provide written informed consent (and assent where applicable) * Willing to comply with study procedures and follow-up for the duration of the study Exclusion Criteria: * Any medical or social condition that, in the opinion of the investigator, would interfere with participation or study procedures * Known allergy or hypersensitivity to any component of the Vi-CRM197 typhoid conjugate vaccine * Parent(s), legal guardian, or participant unwilling or unable to provide informed consent/assent