Participant characteristics.

In 2021–23, a resurgence of malaria occurred in the Tororo District of Uganda following a change in formulations used for indoor residual spraying of insecticide (IRS). Prior analyses showed that this increase was temporally associated with the replacement of Anopheles gambiae sensu lato by An. funestus as the dominant local vector. To investigate this association, we used data from a cohort of 422 children in 94 households from 2021-2023 in Tororo District and neighboring Busia District, where IRS was not implemented. Participants underwent passive and monthly active surveillance for infection with Plasmodium falciparum by quantitative PCR. Mosquitoes were collected in each sleeping room in cohort households every 2 weeks using CDC light traps. We assessed the association between spatiotemporally smoothed annualized household entomologic inoculation rates (aEIR) and individual P. falciparum infections using shared frailty models. Overall, each doubling of the aEIR was associated with a 29% increase in the hazard of P. falciparum (adjusted HR 1.29, 95% CI 1.25-1.33). Considering species-specific aEIRs, this effect was primarily driven by An. funestus: a doubling of An. funestus aEIR was associated with a 29% increase in hazard rate (1.29, 1.25-1.34), while the association was smaller for An. gambiae (1.04, 1.01-1.08). These relationships were stronger in Tororo than in Busia. These results support the inference that the replacement of An. gambiae with An. funestus was a driver of increased malaria incidence in Tororo District and demonstrates associations between household-level entomological data and risk of P. falciparum infection.