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This manuscript is a master statistical analysis plan for each of three-cluster randomized controlled trials to evaluate the efficacy of attractive targeted sugar baits (ATSB) described in an already published protocol. The master SAP contains an overarching plan for all three trials, which can be adapted to trial-specific circumstances. The primary objective of the trials is to evaluate the efficacy of ATSB in the presence of universal vector control coverage with insecticide-treated nets (ITN) or indoor residual spraying (IRS) after two transmission seasons on clinical malaria incidence as compared with universal vector control coverage with ITN or IRS alone. The primary outcome measure is the incidence rate of clinical malaria, assessed in cohorts aged 12 months to less than 15 years (≥ 5 years to 15 years in Mali) during monthly follow-up visits. The primary unadjusted analysis will be conducted on the intention-to-treat analysis population without adjustment for any anticipated confounding variables. The primary outcome will be analyzed using a multi-level model constructed on a generalized linear model framework with a Poisson likelihood and a log link function. Random intercepts will be included for each study cluster and a fixed effect for study-arm. The analyst will be blinded to study arm assignment. Several secondary outcomes will be analyzed, as well as a pooled analysis (individual patient data meta-analysis) across the three trial sites. Additionally, a standard meta-analysis is expected to be conducted using combined data from all sites. [ABSTRACT FROM AUTHOR]

Attractive Targeted Sugar Baits (ATSB) have been demonstrated to result in significant reductions in malaria vector numbers in areas of scarce vegetation cover such as in Mali and Israel, but it is not clear whether such an effect can be replicated in environments where mosquitoes have a wide range of options for sugar resources. The current study evaluated the attractiveness of the predominant flowering plants of Asembo Siaya County, western Kenya in comparison to an ATSB developed by Westham Co. Sixteen of the most common flowering plants in the study area were selected and evaluated for relative attractiveness to malaria vectors in semi-field structures. Six of the most attractive flowers were compared to determine the most attractive to local Anopheles mosquitoes. The most attractive plant was then compared to different versions of ATSB. In total, 56,600 Anopheles mosquitoes were released in the semi-field structures. From these, 5150 mosquitoes (2621 males and 2529 females) of An. arabiensis, An. funestus and An. gambiae were recaptured on the attractancy traps. Mangifera indica was the most attractive sugar source for all three species while Hyptis suaveolens and Tephrosia vogelii were the least attractive plants to the mosquitoes. Overall, ATSB version 1.2 was significantly more attractive compared to both ATSB version 1.1 and Mangifera indica. Mosquitoes were differentially attracted to various natural plants in western Kenya and ATSB. The observation that ATSB v1.2 was more attractive to local Anopheles mosquitoes than the most attractive natural sugar source indicates that this product may be able to compete with natural sugar sources in western Kenya and suggests this product may have the potential to impact mosquito populations in the field. [ABSTRACT FROM AUTHOR]

Background: Long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS) target night-time indoor biting mosquitoes and effectively reduce malaria transmission in rural settings across Africa, but additional vector control tools are needed to interrupt transmission. Attractive targeted sugar baits (ATSBs) attract and kill mosquitoes, including those biting outdoors. Deployment of ATSBs incorporating the insecticide dinotefuran was associated with major reductions in mosquito density and longevity in Mali. The impact of this promising intervention on malaria transmission and morbidity now needs to be determined in a range of transmission settings.Methods/design: We will conduct three similar stand-alone, open-label, two-arm, cluster-randomized, controlled trials (cRCTs) in Mali, Kenya, and Zambia to determine the impact of ATSB + universal vector control versus universal vector control alone on clinical malaria. The trials will use a "fried-egg" design, with primary outcomes measured in the core area of each cluster to reduce spill-over effects. All household structures in the ATSB clusters will receive two ATSBs, but the impact will be measured in the core of clusters. Restricted randomization will be used. The primary outcome is clinical malaria incidence among children aged 5-14 years in Mali and 1-14 years in Kenya and Zambia. A key secondary outcome is malaria parasite prevalence across all ages. The trials will include 76 clusters (38 per arm) in Mali and 70 (35 per arm) in each of Kenya and Zambia. The trials are powered to detect a 30% reduction in clinical malaria, requiring a total of 3850 person-years of follow-up in Mali, 1260 person-years in Kenya, and 1610 person-years in Zambia. These sample sizes will be ascertained using two seasonal 8-month cohorts in Mali and two 6-month seasonal cohorts in Zambia. In Kenya, which has year-round transmission, four 6-month cohorts will be used (total 24 months of follow-up). The design allows for one interim analysis in Mali and Zambia and two in Kenya.Discussion: Strengths of the design include the use of multiple study sites with different transmission patterns and a range of vectors to improve external validity, a large number of clusters within each trial site, restricted randomization, between-cluster separation to minimize contamination between study arms, and an adaptive trial design. Noted threats to internal validity include open-label design, risk of contamination between study arms, risk of imbalance of covariates across study arms, variation in durability of ATSB stations, and potential disruption resulting from the COVID-19 pandemic.Trial Registration: Zambia: ClinicalTrials.gov NCT04800055 . Registered on March 15, 2021 Mali: ClinicalTrials.gov NCT04149119 . Registered on November 4, 2019 Kenya: ClinicalTrials.gov NCT05219565 . Registered on February 2, 2022. [ABSTRACT FROM AUTHOR]