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.2021至2023年间，乌干达托罗罗区因杀虫剂室内滞留喷洒（indoor residual spraying, IRS）配方变更，出现疟疾疫情反弹。既往研究分析表明，此次疫情上升与当地优势传疟媒介由广义冈比亚按蚊复合群（Anopheles gambiae sensu lato）替换为富氏按蚊（An. funestus）存在时间相关性。为探究该关联，本研究使用2021-2023年托罗罗区及未实施IRS的邻近布希亚区94户家庭队列中的422名儿童数据。研究对象通过被动监测与月度主动监测，采用定量聚合酶链反应（quantitative PCR）检测恶性疟原虫（Plasmodium falciparum）感染情况。队列家庭的每间卧室每两周使用CDC诱蚊灯（CDC light traps）采集蚊虫样本。本研究采用共享脆弱模型（shared frailty models），评估经时空平滑处理的家庭年化昆虫接种率（annualized household entomologic inoculation rates, aEIR）与个体恶性疟原虫感染风险之间的关联。总体而言，aEIR每翻倍一次，恶性疟原虫感染的风险比（hazard ratio, HR）升高29%（校正后HR=1.29，95%置信区间（confidence interval, CI）=1.25-1.33）。针对物种特异性aEIR分析显示，该效应主要由富氏按蚊驱动：富氏按蚊aEIR每翻倍一次，感染风险比升高29%（HR=1.29，95%CI=1.25-1.34）；而广义冈比亚按蚊复合群的关联效应较弱（HR=1.04，95%CI=1.01-1.08）。上述关联在托罗罗区的强度高于布希亚区。本研究结果支持“富氏按蚊取代广义冈比亚按蚊复合群是托罗罗区疟疾发病率上升的驱动因素”这一推论，并证实了家庭级昆虫学数据与恶性疟原虫感染风险之间的关联。