Advancing spatial repellents for malaria control: effectiveness and cost-effectiveness of a spatial repellent under operational use in Northern Uganda-study protocol for a cluster randomized controlled trial.

Background: Spatial repellents (SRs) have been widely used for the prevention of mosquito bites, and preliminary findings suggest efficacy against both malaria (1) and Aedes-borne viruses (2) but their effectiveness in reducing mosquito-borne diseases under operational use has never been evaluated. SRs have the potential of being critical tools in the prevention of mosquito-borne diseases in contexts where typical vector control strategies, such as insecticide-treated nets (ITNs) and indoor residual spraying, are inaccessible or underutilized such as among displaced persons or in emergency relief settings.

Methods: Children will be enrolled in 3 separate cohorts to establish the effectiveness of SRs in reducing malaria infection in different distribution channels. One cohort will estimate the direct effect of the SR distributed through a reference channel (study personnel distribution). The two remaining cohorts will estimate the protection of the SR distributed through a voucher channel and the Village Health Team channel. Cohorts will be followed twice a month (approximately every 15 days): during the first scheduled household visit in the month, a blood sample will be taken for malaria rapid diagnostic test (Monthly Visit #1); and, during the second scheduled household visit, a blood sample will only be taken if the participant has a recent history of fever (Monthly Visit #2). The incidence of malaria in each cohort will be estimated and compared to the reference cohort to determine the benefit of using a SR in an area with high, year-round transmission of malaria.

Discussion: This study will address the knowledge gap of whether or not SRs are effective in reducing human malaria disease in humanitarian assistance and emergency response settings in sub-Saharan Africa where underlying transmission rates are historically high and ITNs may or may not be widely deployed. This research will inform policy makers on whether to recommend SRs as a means to further reduce malaria transmission for such operational programs.

Trial registration: ClinicalTrials.gov NCT06122142. Registered on November 8, 2023.