Efficacy and cost-effectiveness of outdoor residual spraying with α-cypermethrin, pirimiphos-methyl, and deltamethrin against sand flies: a pragmatic cluster randomised controlled field trial in Uganda

INTRODUCTION: Visceral leishmaniasis (VL) is a significant public health challenge in East Africa. Achieving the WHO 2030 target of reducing VL mortality to below 1% requires novel control strategies. In this study, we evaluated the efficacy and cost-effectiveness of three insecticide formulations for outdoor residual insecticide spraying (ORS) in selected villages of Amudat district, Uganda. METHODS: A pragmatic clustered randomised controlled field trial was conducted in five clusters. Three clusters were randomly allocated to receive ORS with either α-cypermethrin, pirimiphos-methyl, or deltamethrin, while two clusters served as untreated controls. The primary outcome was the change in sandfly counts per trap-night, measured using CDC light and sticky traps before and after the intervention. These were compared using the Wilcoxon signed-rank test to assess reductions independent of other villages. Then, we used negative binomial regression with a log link of trap-nights to model sandfly counts, which were included as an offset to account for variation in sampling effort. RESULTS: After spraying the insecticides in the intervention villages, the sandfly population declined by 62%, 60%, and 49% with α-cypermethrin, pirimiphos-methyl, and deltamethrin, respectively. Sandfly captures increased by fourfold (353%) in the control villages in the same period. Using a negative binomial regression with village-clustered standard errors, α-cypermethrin reduced sandfly counts by 92% compared to the change in control villages (IRR = 0.08, 95% CI 0.07-0.38, p < 0.001). Pirimiphos-methyl and deltamethrin reduced counts by 91% (IRR = 0.09, 95% CI 0.07-0.45) and 89% (IRR = 0.11, 95% CI 0.10-0.56), respectively. A cost-effectiveness analysis showed that α-cypermethrin emerged as a more cost-effective option, followed by deltamethrin and lastly pirimiphos-methyl, with annual cost per village of $382, $390 and $408, respectively. CONCLUSION: Our findings provide tentative observations that may guide vector control programmes. The relatively high efficacy and favourable cost-effectiveness of α-cypermethrin are suggestive that it could be a suitable option for inclusion in integrated vector management strategies targeting outdoor sandfly populations in this region.