PROJECT SUMMARY Eswatini was among the first countries to achieve the UNAIDS 95, 95, 95 targets resulting in substantial declines in HIV incidence and TB prevalence. Despite this achievement adolescent girls still have a 1.5% annual incidence of HIV infection and the case detection gap for children with TB is estimated to be well over 60%. This highlights the need for new strategies that complement current approaches to HIV and TB prevention and detection. This study will explore HIV and TB wastewater surveillance as a strategy to reignite the drive toward elimination. These pathogens are well suited to wastewater surveillance due to long infectious periods during which patients are asymptomatic and unlikely to present to health facilities for testing. Wastewater measures of TB and HIV from specific sampling areas will ultimately help target public health community case detection interventions. In the first phase of this project, we will establish the pipeline for wastewater surveillance of HIV and TB in Eswatini, building off our experience at Baylor College of Medicine in Houston. The second phase will validate and quantify detection of HIV and TB from multiple sites, establishing variability, a range of quantification, and correlation between the HIV and TB levels detected in wastewater with hospital epidemiology, public health reporting data, and HIV recency testing data. The third phase will establish whether proven public health interventions to increase case detection and treatment initiation for people with TB and HIV will result in reductions in HIV and TB in wastewater samples from those same communities. If successful, this approach has the potential to be a game changing, cost-effective and highly innovative tool in the fight against HIV and TB. The candidate is ideally suited to lead this grant, having a background of proven success in pioneering wet-bench virology and immunology as well as seven years of experience leading epidemiologic and clinical research in Eswatini. This project merges these two areas of experience, and success will require the ability to introduce and adapt wastewater sampling to new pathogens with an in-depth understanding of HIV and TB transmission, epidemiology, and prevention strategies. The team assembled for this project is further evidence of the candidate's ability to assemble strong collaborative teams, drawing together partners from numerous health and environmental programs in Eswatini and colleagues at Baylor College of Medicine. The data generated from this project has the potential to add precision to HIV and TB prevention and case detection strategies and create a platform for wastewater surveillance of other emerging pathogens in Eswatini. Early pathogen detection systems in low-resource environments will ultimately improve health security globally. This strategy, candidate and partners are perfectly positioned to catalyze the elimination of TB and HIV transmission in Eswatini and set the s...