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This dissertation is a history of sleeping sickness research work and prevention programs during the German colonial period in East Africa, focusing on the regions around Lake Victoria and Lake Tanganyika. It examines efforts to study and prevent sleeping sickness, analyzing how both fit into the social, political, and economic dynamics of African life. It covers two phases of German colonial attention to epidemic sleeping sickness between 1902 and 1914: an initial phase of research and scientific expeditions from 1902 to 1906, then a period dominated by the introduction of disease prevention measures in affected areas from 1907 to 1914. Highlighting the local complexity and far-reaching impact of sleeping sickness, I show that sleeping sickness research and prevention emerged from the intersection of tropical medicine expertise, African mobility, and German colonial and African politics. Sleeping sickness, and subsequent efforts toward its treatment and prevention, redefined the boundaries of political power and social influence within African communities during a crucial period of change in the region. By creating new arenas of engagement between African communities and European scientists, specifically in newly-built sleeping sickness camps and among the African medical auxiliaries employed in them, sleeping sickness work created economic relationships, reshaped social and political hierarchies, and set new ground rules for African agriculture and trade. Kings, chiefs, and colonial scientists contended with African communities' demands for treatment, their resistance to examination, and their claims on the use of land and waterways. Further, inter-colonial sleeping sickness research and subsequent prevention programs played a pivotal role in the development of tropical medicine, strengthening disciplinary boundaries and defining the trajectory of future research. My work weaves together narratives of research and disease prevention from metropolitan Europe and East Africa, in contrast to strictly colonial and national histories of health and medicine that have preceded it.