Seroepidemiology of Enteric Fever: Advancing Methods to Characterize the Population-Level Force of Infection in a Changing Global Landscape - PROJECT SUMMARY (ABSTRACT) Enteric fever is caused by the bacteria Salmonella enterica serovars Typhi and Paratyphi (S. Typhi and S. Paratyphi). It remains a significant public health challenge in South Asia, Southeast Asia, and sub-Saharan Africa, particularly affecting children under five years old. In 2017, an estimated 14.3 million cases resulted in approximately 135,900 deaths, imposing substantial healthcare costs and economic burdens on lower- and middle-income countries. Clinical manifestations of enteric fever include prolonged fever, abdominal pain, headache, and malaise, with potential complications such as intestinal perforation, septic shock, and death. Diagnosis remains challenging due to non-specific symptoms and the limitations of current diagnostic methods, which are often expensive, inaccessible, and slow, leading to underreporting and inadequate surveillance. The emergence of antibiotic-resistant strains of S. Typhi further complicates treatment strategies, underscoring the urgent need for effective interventions. Vaccination with the typhoid conjugate vaccine (TCV), which offers over 70% efficacy and up to seven years of protection, presents a viable preventive measure. However, widespread vaccine implementation is hindered by a lack of reliable epidemiological data to inform policy decisions. Seroepidemiology, the collection and analysis of data on the presence and quantity of antibodies in blood to study the distribution and determinants of infection in populations, can provide cost-effective tools to estimate seroconversion rates and better understand infection dynamics, facilitating targeted vaccine deployment. New methods are available that using quantitative antibody responses to HlyE and LPS antigens to characterize seroconversion rates in population-based samples. However, several important limitations remain to scale these methods to inform and evaluate public health interventions. This project aims to address critical gaps in enteric fever surveillance by advancing seroepidemiological methods to support disease detection and prevention. Aim 1 will develop a method to accurately characterize enteric fever seroconversion rates in settings with high disease burden and frequent re-exposures. Aim 2 will extend these methods geospatially identify populations with the highest enteric fever seroconversion rates. Aim 3 will develop a novel method to distinguish S. Typhi from S. Paratyphi based on quantitative antibody responses and modeled antibody decay curves. This pre-doctoral research will enhance the accuracy of seroepidemiological methods for enteric fever, informing vaccine introduction and other disease prevention efforts. The accompanying training plan will to provide the trainee in with the skills and professional expertise necessary for a successful career as an independent academic researcher.
