SUMMARY/ABSTRACT Due to challenges with available technology in regions of the world where schistosomiasis is endemic, the prevalence of schistosomiasis-associated pulmonary arterial hypertension (SchPAH) is unknown. SchPAH is an incurable and ultimately fatal disease for which early detection and treatment could extend the lives of those afflicted. New approaches to diagnose SchPAH are needed, as the current diagnostic criteria require invasive right heart catheterization leading to under and delayed diagnosis. An opportunity to develop noninvasive diagnostic risk scores for PAH is provided by the PVDomics dataset and a collaboration to conduct these analyses at UCSF using the PVDomics data has been established. The proposed studies will define diagnostic risk scores for PAH (i) using a broad range of clinical, echocardiographic (echo), and biomarker predictors and (ii) using predictors easily measured in low- and middle-income countries (LMIC). The risk scores would enable estimation of the probability of PAH in individuals, the PAH case-rate in clinic samples, and PAH prevalence in communities at risk. Regardless of LMIC, the scores will rely only on noninvasive predictors to support their repeated use in disease screening. After developing the risk score, its first application to will be to SchPAH disease, and will take place in the longitudinal prospective cohorts we are enrolling at 3 clinical sites in Ethiopia and Zambia, targeting 40 enrollees per site per year. We will estimate the case-rate of SchPAH by standard of care criteria and using the Aim-1 diagnostic risk score. Eligible patients will have a history of Schistosoma infection and be diagnosed with schistosomiasis-associated hepatosplenic disease (SchHSD), placing them at relatively high risk for SchPAH. At baseline and annual follow-up study visits each participant will undergo clinical and echocardiography assessments, and providing blood samples for biomarker assessments to ensure that the predictors on which the diagnostic score is based are on hand. Once it is defined, the risk score and probability of PAH will be calculated on each participants’ data, both at past and future visits, and the distribution the quantities will be summarized graphically. This study also will evaluate some biomarkers that reflect the pathobiology of SchPAH and may be particularly suitable for identifying PAH disease during its preclinical and early clinical periods, which could suggest a role as potential therapeutic targets. We believe these diagnostic tools will have enormous impact on all those worldwide who are at risk for developing PAH or living with undiagnosed PAH.