Adaptive intervention strategies for malaria vector control in western Kenya: a cluster, sequential,...

Many regions in Africa continue to experience a high malaria burden, highlighting the need for improved intervention tools adapted to local eco-epidemiological contexts. The aims of this study were to develop and evaluate adaptive intervention strategies for malaria vector control tailored to these local conditions.

This two-stage, cluster, sequential, multiple-assignment, randomised, open-label trial comprised 84 clusters in Muhoroni and Nyakach, subcounties of Kisumu County, western Kenya. Each cluster included 500-600 residents in an area of approximately 2 km² and all residents in the clusters were invited to participate in the study. In stage 1, clusters were randomly assigned, in a 1:1:1 ratio, to standard pyrethroid-based long-lasting insecticidal nets (LLINs; henceforth standard LLINs) alone, piperonyl butoxide-treated LLINs (henceforth PBO nets), or standard LLINs plus annual indoor residual spraying (IRS), stratified by subcounty. Due to the nature of the interventions, masking to intervention was not feasible. Clusters with an adjusted incidence rate ratio (aIRR) of 0·8 or more were classified as non-responders. Non-responding clusters were re-randomised in stage 2. The non-responding clusters from the stage 1 PBO nets group were re-randomised, in a 1:1 ratio, to receive either supplemental microbial larviciding or annual IRS. The non-responding clusters from the stage 1 standard LLINs plus annual IRS group were re-randomised, in a 1:1 ratio, to either IRS twice per year (henceforth biannual IRS), or enhanced IRS annually, which included spraying both indoor residential structures and peridomestic resting structures not covered by routine IRS. The coprimary outcomes were clinical malaria incidence at 1-6 months, 7-12 months, and 13-18 months post-intervention, assessed through active surveillance of cohort populations once every 2 weeks and analysed in all participants with available data. Although the study procedures posed minimal risk to participants, adverse event data were regularly reviewed. The trial was registered with ClinicalTrials.gov (NCT04182126) and is complete.

Between March 8, 2021, and Aug 31, 2024, the study enrolled 47 614 participants (51·8% male, 48·2% female) from 14 246 households in 84 clusters. In stage 1, PBO nets significantly reduced malaria incidence at 1-6 months post-intervention (aIRR 0·75, 95% CI 0·69-0·81; p<0·0001) and at 7-12 months post-intervention compared with standard LLINs (aIRR 0·87, 95% CI 0·80-0·95; p=0·0012), and standard LLINs plus annual IRS was more effective than standard LLINs alone at 1-6 months (aIRR 0·74, 95% CI 0·68-0·81; p<0·0001). In stage 2, among stage 1 non-responding clusters, adding annual IRS to PBO nets was more effective than supplementing with larviciding at 13-18 months (aIRR 0·89, 95% CI 0·81-0·97; p=0·0081). When added to standard LLINs, enhanced IRS was more effective than biannual IRS 13-18 months post-intervention (aIRR 0·67, 95% CI 0·56-0·80; p<0·0001). Overall, the four adaptive intervention strategies significantly reduced clinical malaria incidence compared with standard LLINs (all p<0·01). Adaptive strategies starting with PBO nets had greater and more sustained incidence reductions than strategies beginning with standard LLINs plus annual IRS. No adverse events or serious adverse events were recorded.

This trial supports replacing conventional pyrethroid-only LLINs with PBO nets as the first-line malaria control strategy. In moderate-to-high-risk settings, additional annual IRS or microbial larviciding could be implemented to further reduce malaria burden.

US National Institutes of Health.

For the Swahili translation of the abstract see Supplementary Materials section.