This chapter examines several ongoing debates about vector and parasite, focused on zoonotic and animal trypanosomiasis in eastern and southern Africa. Trypanosomiasis is a devastating vector-borne disease of both humans and animals. It is, multiple diseases, involving various trypanosomes, protozoan parasites carried by different variants of the tsetse fly. Colonial authorities were horrified by the consequences of human trypanosomiasis or sleeping sickness, investing huge effort and resources in trying to tackle it. Trypanosomiasis is an ideal candidate for a One Health approach. The different fly vectors are highly dependent on particular habitats for their survival, and so ecological and land use change has a major impact on fly populations, and the associated disease risks. In a global policy debate centred on an inclusive politics of collaboration and integration, the history of trypanosomiasis and tsetse research and control reminds us of how prevailing institutional politics and entrenched interests remain very much embedded within narrow scientific and practitioner networks.