PROJECT SUMMARY / ABSTRACT The typhoidal Salmonellas (TS), primarily Salmonella Typhi and Paratyphi A, are a major cause of global morbidity and mortality, particularly in Asia where widespread antimicrobial resistance is an increasing concern. The Indo-Pacific is endemic for TS and vulnerable to these infections due to suboptimal surveillance networks, insufficient sanitation and hygiene infrastructure, and lack of support for interventions to reduce TS burden (vaccine only targets S. Typhi, is not widely accessible, and indirect protection may be modest). This region is at increased risk for TS due to disproportionate susceptibility to hydrologic events (drought, flooding) associated with climate change. Predicting TS transmission and evaluating interventions to reduce TS risk in the setting of a changing climate is critical. Water, sanitation, and hygiene (WASH) improvements decrease TS burden through reduced fecal contamination of the environment. However, trials of WASH interventions often target the household-level (e.g., behavioral interventions, kitchen water filters) and are limited in reproducibility and generalizability, frequently using non-specific surrogate markers of human health. Revitalizing Informal Settlements and their Environments (RISE) is a cluster-randomized controlled trial of community-level WASH infrastructure upgrades currently underway in 24 informal urban settlements in Indonesia and Fiji, two countries with high TS risk. RISE provides an ideal opportunity to study targeted solutions to reduce TS burden and evaluate their impact. Utilizing RISE-collected samples, the research detailed in this proposal uses: Aim 1) novel serosurveillance techniques to estimate “seroincidence” as a surrogate for TS incidence and Aim 2) genomic methods to identify TS in human and environmental microbiomes. To inform improved future interventions under different scenarios, these data will be used to: Aim 3) establish compartmental modeling approaches to predict and assess the impact of WASH interventions on TS transmission and ultimately disease reduction. The candidate is an infectious diseases fellow with a background in molecular biology, genomics, computational biology, and global health research. The candidate’s primary career goal is to be an independent NIH-funded physician-scientist committed to developing, assessing, and implementing interventions aimed at controlling TS and other infectious diseases that disproportionately impact populations in resource-constrained settings. To achieve independence, the candidate requires targeted mentoring and additional training in: 1) laboratory methods and field research management, 2) advanced bioinformatics analysis and infectious diseases modeling, and 3) research communication and impact. The proposed research and training plans will be supervised by primary mentor Dr. Stephen Luby, a global health clinical research expert and PI of RISE. Dr. Jason Andrews (seroepidemiology, modeling) w...