Impact of indoor residual spraying and insecticide-treated nets on malaria burden in 8 districts in West Nile and Acholi regions, Uganda: a quasi-experimental study

BACKGROUND: In Uganda, where malaria transmission is high, insecticide treated nets (ITNs) have been distributed nationwide every 3 years since 2013. In West Nile, northern Uganda, indoor residual spraying (IRS) was first implemented with clothianidin-deltamethrin (Fludora Fusion®) in 2022, followed by pirimiphos-methyl (Actellic® 300CS) in 2023. We utilised a quasi-experimental study to assess the impact of IRS + ITNs on malaria incidence in West Nile. METHODS: Data were collected from three malaria reference centres (MRCs) in West Nile (IRS + ITNs, intervention) and five MRCs in neighbouring Acholi (ITNs only, control) over 4 years: (1) Baseline (December 2020-November 2022), prior to IRS; (2) IRS-1 (December 2022-December 2023) following IRS with clothianidin-deltamethrin; (3) IRS-2 (January 2024-December 2024) following IRS with pirimiphos-methyl. The primary outcome was monthly malaria incidence from each MRC target area per 1000 person-years. Data were analysed using negative binomial regression models with a difference-in-difference approach, comparing pre-post trends in malaria incidence between arms. Adjusted models accounted for 2-month lagged rainfall and seasonality. RESULTS: During IRS-1, mean observed malaria incidence fell from baseline in both arms (intervention: 720.9 to 547.9; and control: 523.4 to 455.2 per 1000 person-years). We detected a 15% difference in predicted mean incidence between arms during IRS-1 relative to baseline, but this was not significant (adjusted incidence rate ratio (aIRR) = 0.85, 95% confidence interval (CI) 0.69-1.04, p = 0.11). During IRS-2, incidence in the intervention arm declined by 79.3% compared to baseline (720.9 to 149.1), and by 24.3% (523.4 to 396.2) in the control arm. We detected a 73% reduction in predicted mean malaria incidence in the intervention arm compared to control relative to baseline (aIRR = 0.27, 95% CI 0.22-0.34, p < 0.001). During IRS-2, there was strong evidence of an immediate and sustained reduction in incidence in the intervention arm over 1 year. CONCLUSIONS: In West Nile, the reduction in malaria incidence after clothianidin-based IRS (plus ITNs) was modest and non-significant. Subsequent IRS with pirimiphos-methyl (plus ITNs) substantially reduced malaria incidence. These results highlight the importance of selecting context-specific insecticides for vector control programmes and the potential synergistic effect of dual interventions in areas of high pyrethroid resistance.