Widespread transmission in diverse ecotypes challenges visceral leishmaniasis control in East Africa.

East Africa is emerging as the global hot spot of visceral leishmaniasis (VL), yet efforts to eliminate it are hindered by substantial knowledge gaps in its ecoepidemiology. Here, we report on the high prevalence of Leishmania infection in Phlebotomus orientalis in Marsabit county, Kenya (3.9%), and Gedaref state, Sudan (3.6%), where this species comprised 99.8% (n = 1185) and 100% (n = 1350) of captured Phlebotomus females, respectively. In Aba Roba, Ethiopia, Ph. martini accounted for 99% of 184 collected Phlebotomus females and had a lower infection rate of 1.5%. Ph. orientalis and Ph. martini exhibited different habitat and feeding preferences. While Ph. orientalis was abundant in diverse peridomestic and sylvatic microhabitats, Ph. martini was predominantly collected from termite hills. Moreover, Ph. orientalis primarily fed on humans and less on domestic and sylvatic animals. In contrast, Ph. martini exhibited zoophagic behavior, mostly feeding on cows and Ovis. Widespread transmission of Leishmania in our study sites is supported by high rK39 seroprevalence in both Kenya (17.9%) and Sudan (6.22%). An observed greater prevalence of antibodies to rK39 in individuals living near than away from VL cases in both Kenya (19.8% versus 7.41%, P = 0.0015) and Sudan (8.4% versus 2.1%, P = 0.0105) demonstrated that proximity to a VL case carries an increased risk of infection. Our findings highlight the need for a risk-based targeted site-specific elimination strategy that accounts for the intensity, diversity, and complexity of VL transmission in today's East Africa.