Attractive targeted sugar bait phase III trials in Kenya, Mali, and Zambia.

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. 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. 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. 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.

Attractive Targeted Sugar Bait Phase III Trial Group 《Trials》

Efficacy of attractive targeted sugar bait stations against malaria in Western Province Zambia: epidemiological findings from a two-arm cluster randomized phase III trial.

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. 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. 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. 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. The trial is registered with Clinicaltrials.gov (NCT04800055).

Ashton RA ，Saili K ，Chishya C ，Banda Yikona H ，Arnzen A ，Orange E ，Chitoshi C ，Chulu J ，Tobolo T ，Ndalama F ，Kyomuhangi I ，Ngulube W ，Moonga H ，Chirwa J ，Slutsker L ，Wagman J ，Chanda J ，Miller J ，Silumbe K ，Hamainza B ，Eisele TP ，Yukich J ，Littrell M ... -  《-》

Adaptive interventions for optimizing malaria control: an implementation study protocol for a block-cluster randomized, sequential multiple assignment trial.

Zhou G ，Lee MC ，Atieli HE ，Githure JI ，Githeko AK ，Kazura JW ，Yan G ... -  《Trials》

Characteristics of the Western Province, Zambia, trial site for evaluation of attractive targeted sugar baits for malaria vector control.

Arnzen A ，Wagman J ，Chishya C ，Orange E ，Eisele TP ，Yukich J ，Ashton RA ，Chanda J ，Sakala J ，Chanda B ，Muyabe R ，Kaniki T ，Mwenya M ，Mwaanga G ，Eaton WT ，Mancuso B ，Mungo A ，Mburu MM ，Bubala N ，Hagwamuna A ，Simulundu E ，Saili K ，Miller JM ，Silumbe K ，Hamainza B ，Ngulube W ，Moonga H ，Chirwa J ，Burkot TR ，Slutsker L ，Littrell M ... -  《MALARIA JOURNAL》

Residual bioefficacy of attractive targeted sugar bait stations targeting malaria vectors during seasonal deployment in Western Province of Zambia.

The primary vector control interventions in Zambia are long-lasting insecticidal nets and indoor residual spraying. Challenges with these interventions include insecticide resistance and the outdoor biting and resting behaviours of many Anopheles mosquitoes. Therefore, new vector control tools targeting additional mosquito behaviours are needed to interrupt transmission. Attractive targeted sugar bait (ATSB) stations, which exploit the sugar feeding behaviours of mosquitoes, may help in this role. This study evaluated the residual laboratory bioefficacy of Westham prototype ATSB® Sarabi v.1.2.1 Bait Station (Westham Ltd., Hod-Hasharon, Israel) in killing malaria vectors in Western Province, Zambia, during the first year of a large cluster randomized phase-III trial (Clinical Trials.gov Identifier: NCT04800055). This was a repeat cross-sectional study conducted within three districts, Nkeyema, Kaoma, and Luampa, in Western Province, Zambia. The study was conducted in 12 intervention clusters among the 70 trial clusters (35 interventions, 35 controls) between December 2021 and June 2022. Twelve undamaged bait stations installed on the outer walls of households were collected monthly (one per cluster per month) for bioassays utilizing adult female and male Anopheles gambiae sensu stricto (Kisumu strain) mosquitoes from a laboratory colony. A total of 84 field-deployed ATSB stations were collected, and 71 ultimately met the study inclusion criteria for remaining in good condition. Field-deployed stations that remained in good condition (intact, non-depleted of bait, and free of dirt as well as mold) retained high levels of bioefficacy (mean induced mortality of 95.3% in males, 71.3% in females, 83.9% combined total) over seven months in the field but did induce lower mortality rates than non-deployed ATSB stations (mean induced mortality of 96.4% in males, 87.0% in females, 91.4% combined total). There was relatively little variation in corrected mortality rates between monthly rounds for those ATSB stations that had been deployed to the field. While field-deployed ATSB stations induced lower mortality rates than non-deployed ATSB stations, these stations nonetheless retained relatively high and stable levels of bioefficacy across the 7-month malaria transmission season. While overall mean mosquito mortality rates exceeded 80%, mean mortality rates for females were 24 percentage points lower than among males and these differences merit attention and further evaluation in future studies. The duration of deployment was not associated with lower bioefficacy. Westham prototype ATSB stations can still retain bioefficacy even after deployment in the field for 7 months, provided they do not meet predetermined criteria for replacement.

Mwaanga G ，Ford J ，Yukich J ，Chanda B ，Ashton RA ，Chanda J ，Munsanje B ，Muntanga E ，Mulota M ，Simuyandi C ，Mulala B ，Simubali L ，Saili K ，Simulundu E ，Miller J ，Hamainza B ，Orange E ，Wagman J ，Mburu MM ，Harris AF ，Entwistle J ，Littrell M ... -  《-》