PROJECT SUMMARY / ABSTRACT: Burkina Faso ICEMR Research Project 1 Burkina Faso has the 6th highest mortality and morbidity from malaria despite aggressive multifaceted control interventions including rapid diagnosis and treatment, bed nets, indoor residual spraying, intermittent preventive treatment in pregnancy, and seasonal malaria chemoprevention. While Plasmodium falciparum continues to be the focus of control programs and most clinical and epidemiologic studies, our group, and others, have gathered data from several settings across sub-Saharan Africa, including from Burkina Faso, demonstrating a notable prevalence of non-falciparum mono- and mixed infections that is persistent and robust. In particular, Plasmodium malariae, with its longer 72-hour life cycle, and P. ovale, with its dormant hypnozoite stages, both tend to maintain low parasite densities, go undetected with current point-of-care diagnostics, and are undertreated due, in part, to a lack of evidence regarding their sensitivity to currently utilized antimalarials. In addition, due to insensitivity of current diagnostics, our understanding of their dynamics and multi-species interactions in the host remain largely unstudied using state-of-the-art molecular tools. Through our project, and synergy with the rest of the Burkina Faso ICEMR, we will leverage a novel surveillance approach, known as xenosurveillance, to first characterize the epidemiology of all human species via testing of mosquito blood meals. Following this initial spatiotemporal analysis of parasite and vector diversity throughout three distinct ecozones in Burkina Faso, we will select a subset of sites in each zone to conduct longitudinal household-based cohorts over three years. The goal of these studies will be to carefully characterize the epidemiology and clinical impact of mono- and mixed species infections and to understand the performance of current diagnostics for detecting the symptomatic and asymptomatic reservoir of infection. We will utilize samples from these cohort to further elucidate the population structure of circulating Plasmodium species, and characterize their ex vivo and genetic resistance profiles to current and promising antimalarials. Our ultimate goal is to create a sustainable multidisciplinary malaria surveillance system across the Sahel, Sudan-Sahel, and Sudan regions of Burkina Faso that simultaneously characterizes vector, host and parasite epidemiology, with explicit inclusion of all human parasite species in circulation, and through synergy with Project 2 of the ICEMR, to characterize the role of primary and secondary vectors in perpetuating this complex multi-species malaria transmission cycle.