Adjusting vector surveillance for human behaviors reveals Anopheles funestus drove a resurgence in malaria despite IRS with clothianidin in Uganda.

After remarkable success following the implementation of indoor residual spraying (IRS) and repeated rounds of universal distribution of insecticidal treated nets in Tororo District, eastern Uganda, a switch to clothianidin-based IRS in March 2020 was associated with a resurgence of malaria transmission. A previous study suggested Anopheles funestus may be driving the resurgence. This study was undertaken to assess the role of An. funestus in the resurgence and improve our understanding of how human-vector interaction affects malaria transmission in settings with extensive vector control. Using human landing catches and human behavioral observations, we found An. funestus infective biting, calculated from human-behavior adjusted biting rates and species-specific sporozoite rates, was 4.3 (95% Confidence Interval [CI]: 1.81 to 10.33) times higher after multiple rounds of clothianidin-based IRS when transmission was high and then dropped off markedly with a switch back to the organophosphate Actellic in March 2023. This finding was bolstered by a causal analysis showing a link between clothianidin-based IRS and 8.6 (95% CI: 2.0 to 37.0) times higher human-behavior adjusted human biting rates due to An. funestus. These findings highlight the importance of integrating monitoring of human-vector interaction and vector bionomics when introducing or evaluating changes in vector control interventions.