Novel tools for measuring typhoid vaccine impact

Project Summary Typhoid fever is a leading cause of invasive bacterial illness and death worldwide, with the majority of infections occurring in low- and middle-income countries where water and sanitation infrastructure is poor. Highly antimicrobial-resistant strains of Salmonella Typhi have been emerging and spreading internationally and intercontinentally, posing the risk of rising morbidity among reduced effectiveness of therapy. New typhoid conjugate vaccines have demonstrated a high level of effectiveness and are recommended by the WHO; however, many countries lack data on typhoid incidence, as the only reliable tool for typhoid diagnosis—blood culture—is not widely available in many resource-constrained settings where typhoid risk may be greatest. To address these gaps, we propose to leverage a large, cluster-randomized trial of a typhoid conjugate vaccine being performed in Vellore, India, to test three emerging tools to measure community burden of typhoid: 1) seroepidemiological models, utilizing recently characterized seroresponses to S. Typhi antigens; 2) detection of S. Typhi-specific bacteriophages in wastewater, using low-cost assays; 3) phylodynamic methods that track measures of transmission intensity. This project will provide rigorous testing of multiple innovative methods amid uniquely intensive clinical surveillance in a vaccine trial. Overall, this project will address a critical need for public health tools to make typhoid surveillance scalable in resource-constrained settings, to inform vaccine introductions and monitor their impact.