PROJECT 1 SUMMARY Despite the deployment of proven malaria control interventions, malaria incidence in Cameroon has been increasing since 2012, ranking among the top 11 high-burden countries. The failure of current interventions to effectively reduce the malaria burden in Cameroon is evident, necessitating the urgent search for evidence to support the rational design and implementation of effective control strategies. The reasons for this failure are likely complex due to Cameroon's diverse eco-climatic settings and corresponding divergent malaria epidemiology. Therefore, the overall goal of this project is to characterize malaria transmission across various epidemiological settings in Cameroon where different interventions are being implemented and determine the underlying mechanism for the epidemics of Plasmodium vivax malaria. We hypothesize that current region-specific interventions in Cameroon do not effectively target the critical transmission reservoirs to reduce malaria transmission. To test this hypothesis, we will conduct longitudinal cohort studies and entomological assessments to elucidate the critical transmission reservoirs, evaluate the impacts of different interventions on the reservoirs, the vectorial system, and the spatiotemporal evolution of parasite populations, and identify key factors responsible for persistent malaria transmission. This research will be conducted in strategically selected sites located in different eco-climatic zones where different control interventions (e.g., different types of bednets, RTS,S vaccine, seasonal vs. perennial malaria chemoprevention) are implemented. Specifically, we will (1) conduct longitudinal cohort studies and mosquito feeding experiments to elucidate the critical transmission reservoirs for both P. falciparum and P. vivax malaria; (2) investigate the impact of the different interventions on vector community, biting behavior, and vectorial capacity and correlate these changes with disease incidence; and (3) determine how malaria interventions impact the spatiotemporal evolution of parasite populations using population genomics. The findings from these studies will provide insights into the underlying mechanisms responsible for the persistent high-level malaria transmission in different ecological settings and inform the development, evaluation, and implementation of integrated malaria management strategies in Cameroon and other high-burden countries to reduce the malaria burden.