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Abstract Background Attractive targeted sugar bait (ATSB) stations containing bait (to attract) and ingestion toxicant (to kill) sugar-foraging mosquitoes are hypothesized to reduce malaria transmission by shortening the lifespan of Anopheles vectors. Methods A two-arm cluster-randomized controlled trial (cRCT) was conducted in Western Province Zambia. Seventy clusters of 250–350 households were assigned (1:1) by restricted randomization to an intervention arm (ATSB) or control arm (no ATSB) in the context of standard of care vector control (insecticide-treated nets and/or indoor residual spraying). Two ATSB stations (Westham Sarabi, 0.11% dinotefuran w/w) were maintained on exterior walls of eligible household structures for a 7-month deployment period (December-June) during the high malaria transmission season. The primary outcome was clinical malaria incidence among two consecutive seasonal cohorts of children aged 1–14 years, followed-up monthly from January-June in 2022 and 2023. Secondary outcome was Plasmodium falciparum prevalence among individuals aged over six months. Analysis compared clinical malaria incidence and prevalence between arms among the intention-to-treat population. Results ATSB coverage, assessed by cross-sectional survey, was 98.3% in March–April 2022 and 89.5% in March–April 2023. 4494 children contributed any follow-up time to the cohort, with 2313 incident malaria cases in the intervention arm (1.28 per child per six-month transmission season), and 2449 in the control arm (1.38 per child-season). The incidence rate ratio between the two arms was 0.91 (95% CI 0.72–1.15, p = 0.42). 2536 individuals participated in cross-sectional surveys, with prevalence of P. falciparum 50.7% in the intervention arm and 53.5% in the control arm. The odds ratio between the two arms was 0.89 (95% CI 0.66–1.18, p = 0.42). Secondary covariable-adjusted and subgroup analyses did not substantially alter the findings. No serious adverse events associated with the intervention were reported. Conclusions Two ATSB stations deployed per eligible structure for two consecutive transmission seasons did not result in a statistically significant reduction in clinical malaria incidence among children aged 1–14 years or in P. falciparum prevalence in rural western Zambia. Further studies are needed to assess the efficacy of ATSB stations in different settings and with different deployment strategies. Trial registration The trial is registered with Clinicaltrials.gov (NCT04800055).

Abstract Background Some settings continue to experience a high malaria burden despite scale-up of malaria vector control to high levels of coverage. Characterisation of persistent malaria transmission in the presence of standard control measures, also termed residual malaria transmission, to understand where and when individuals are exposed to vector biting is critical to inform refinement of prevention and control strategies. Methods Secondary analysis was performed using data collected during a phase III cluster randomized trial of attractive targeted sugar bait stations in Western Province, Zambia. Two seasonal cohorts of children aged 1–14 years were recruited and monitored monthly during the malaria transmission season, concurrent with entomological surveillance using a combination of human landing catch (HLC) and Centres for Disease Control (CDC) light traps at randomly selected households in study clusters. Behavioural data from cohort participants were combined with measured Anopheles funestus landing rates and sporozoite positivity to estimate the human behaviour-adjusted entomological inoculation rate (EIR). Results Behavioural data from 1237 children over 5456 child-visits in 20 entomology surveillance clusters were linked with hourly landing rates from 8131 female An. funestus trapped by HLC. Among all An. funestus tested by enzyme-linked immunosorbent assay (ELISA), 3.3% were sporozoite-positive. Mean EIR directly measured from HLC was 0.07 infectious bites per person per night (ib/p/n). When accounting for child locations over the evening and night, the mean behaviour-adjusted EIR was 0.02 ib/p/n. Children not sleeping under insecticide-treated nets (ITNs) experienced 13.6 infectious bites per person per 6 month season, 8% of which occurred outdoors, while ITN users received 1.3 infectious bites per person per 6 month season, 86% of which were received outdoors. Sleeping under an ITN can prevent approximately 90% of potential An. funestus bites among children. Conclusions In this setting ITNs have a high personal protective efficacy owing to peak An. funestus biting occurring indoors while most individuals are asleep. However, despite high household possession of ITNs (>90%) and high individual use (>70%), children in this setting experience more than one infectious bite per person per 6 month transmission season, sufficient to maintain high malaria transmission and burden. New tools and strategies are required to reduce the malaria burden in such settings. Graphical Abstract