Outdoor attractive targeted sugar bait Phase III trials for malaria control in Kenya, Mali, and Zambia: An individual participant data meta-analysis

Attractive targeted sugar baits (ATSB) are a potential new class of vector control tool that act through an "attract and kill" mechanism on mosquitoes. We conducted a meta-analysis using data from three large-scale Phase III trials of the Westham Sarabi v1.2 ATSB (0.11% dinotefuran) conducted in Kenya, Mali, and Zambia, to determine the effect of the intervention on clinical malaria incidence in children, Plasmodium falciparum infection prevalence, and dominant vector species parity, abundance, landing rate, and sporozoite positivity. The Sarabi ATSB was deployed on exterior walls at the rate of two per residential structure. Aggregated and individual-level meta-analyses were completed for each of the six trial outcomes, comprising 6981 person-years of follow-up for clinical malaria incidence (primary epidemiological outcome) and 19443 Anopheles for parity assessment (primary entomological outcome). Post-hoc analyses included assessment of dose-response relationships between coverage-adjusted intervention density and clinical malaria incidence. There were no statistically significant differences between arms in any of the epidemiological or entomological outcomes. There was statistically significant evidence of a 19% reduction in clinical malaria incidence for every 10 bait stations per hectare increase observed in spatial density (IRR 0.81, 95% CI 0.74-0.89, p<0.001), provided that the ATSB were in good condition. This finding suggests that there may be deployment approaches or dosing strategies under which ATSB tools could be efficacious, although threshold spatial densities could not be determined from available data. This meta-analysis furthermore highlights important recommendations for future cluster-randomized trials of vector control interventions, including conducting comprehensive baseline data collection to identify cluster outliers or sites with differences in vector bionomics, and collecting a limited set of entomological outcomes in all trial clusters to ensure an adequately powered and balanced analysis of entomological effects.