PROJECT 1 SUMMARY Wide deployment of malaria control tools in the past decade, has significantly contribute to substantial reduction of the incidence and deaths related to the disease in Sub-sahara Africa (ref). Yet, the region continues to carry a disproportionately high share of the global malaria burden of malaria deaths. Moreover incidence remains high but stable in some settings while rebounding in others after a long period of decrease associated with intensive deployment of malaria control tools. The gap in our knowledge that this project will fill is information on the relationships interaction among current combination of malaria control interventions, entomologic aspects of transmission and the incidence of human infection and disease in different eco-zones across West Africa that span the savanna and sub-Saharan Sahel region. The goal of this project is to understand why different patterns of malaria epidemiology and endemicity are resilient to current control strategies at four sites in Mali. The four field sites exhibit different endemicities, length of seasonality, and different combinations of control interventions and duration of implementation of those interventions. The specific aims are 1] Determine a cohort-based long-term effect of concurrent malaria control interventions on the incidence of uncomplicated and severe malaria in relation with asexual an sexual malaria infections at 4 ecological settings with different combination of malaria control interventions in West Africa; 2] Determine seasonal changes in malaria vector population composition, biting behavior and sporozoite rates in relation with ongoing vector control tools deployed on each ecological setting; 3] Assess the relationships between temporal and spatial variations in vector epidemiological parameters, and P. falciparum infection and disease in human populations. This project links the different aspects of malaria transmission and disease into a unified whole, adding the ability to distinguish the contributions of different malaria control interventions on parasite population and range of immune responses (Project 2, Immunopahtogenesis) and seasonal and geographical distribution of Anopheline mosquitoes vectors (Project 3). Understanding the factors relating entomologic and epidemiological patterns of transmission will provide more definitive guidelines for malaria control efforts in Mali and in West Africa.