PROJECT 1 PROJECT SUMMARY Impact of Environmental Modifications on Plasmodium falciparum and P. vivax Malaria Epidemiology and Disease Burden Severe droughts have plagued the African continent for centuries. Most people in African countries depend on rain-fed agriculture, making these populations vulnerable to drought and famine. Construction of dams and initiating rural irrigation schemes has been widely recognized as key solutions to food security and economic growth in drought prone regions. In the past decade, sub-Saharan African countries have experienced a new era of large dam constructions and expansion of irrigated agricultural farms. These environmental changes may have unforeseen ecologic consequences that adversely affect human health. To date, there has been limited basic or translational research evaluating the impact of environmental modifications on the epidemiology of malaria. The overarching objective of this project is to assess the impact of environmental modifications from water resource development projects and shifting agricultural practices on the change of epidemiology of malaria at the molecular, individual, field and population levels. The central hypothesis is that ecological changes and large-scale human population movement resulting from dam construction, flooding of the dam catchment and shifting of agriculture practices will modify the transmission and risk of malaria in the area. We will test this hypothesis by monitoring ecological changes, conducting repeated cross-sectional surveys and longitudinal cohort studies in the community, and passive surveillance for malaria in health centers and hospitals. The three specific aims are to: 1) compare symptomatic malaria burden and spectrum of disease severity in areas of diverse eco-epidemiologic settings with drastic environmental modifications and differing prevalence of Plasmodium species, 2) examine the effect of human migration associated with construction of dams and irrigation farming on the landscape genetics of malaria parasites, and 3) assess the effectiveness of recently introduced primaquine treatment strategies on the risk of Plasmodium vivax recurrence and P. falciparum transmission under different environmental conditions in Ethiopia. Because the irrigated area of sub-Saharan Africa and the number of large hydropower dams are anticipated to increase dramatically in the next decade, understanding the impact of water development projects on malaria epidemiology and subsequently developing strategies to reduce transmission and morbidity will be of paramount importance. Although this study is conducted only in highly populated areas in Kenya and Ethiopia, we anticipate that our findings and tools will have broad implications for malaria prevention and control in other regions of sub-Saharan Africa that are undergoing similar environmental modifications.