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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.

Vector control is an essential component of malaria prevention that has contributed to the reduction in malaria burden since 2000. Although steady progress in malaria vector control has been achieved over the years, the malaria burden remains substantial, underscoring the need for complementary mosquito control tools to further reduce transmission. Attractive targeted sugar baits (ATSBs) are a novel vector control tool under evaluation. The ATSB paradigm leverages the sugar feeding and resting behavior of mosquitoes exposing them to the lethal effect of an added insecticide. Prior to epidemiological trials on ATSBs in western Kenya, validation studies were conducted to assess the levels of mosquito feeding on attractive sugar baits (ASBs), containing uranine dye. This study sought to understand the ATSB deployment required in peridomestic spaces and to determine the daily feeding rates that would be potentially sufficient to impact malaria transmission (based on modelling approaches). The study evaluated whether the deployment of two versus three bait stations per structure led to higher daily feeding rates by local malaria vectors that is consistent with the modelled threshold of 2.5% of all mosquitoes in the target area as a proxy for ATSB efficacy resulting in a 30% drop in clinical incidence in children under 5. The study followed a cross-over design in ten treatment and two control clusters within Rarieda Sub-County, Siaya County, western Kenya. Within each intervention cluster, either two or three ASBs were deployed to all structures in each cluster. After two months, the treatments were switched so that clusters which initially received two ASBs were given three ASBs and vice versa. ASB monitoring was done for four months during the initial crossover trial and then for an additional four months for extended monitoring. Mosquitoes were collected using ultraviolet CDC light traps and Prokopack aspiration indoors and outdoors then identified based on morphological characteristics and screened for fluorescence due to the uranine dye. Molecular species identification was done using polymerase chain reaction and sporozoite infectivity tests by Enzyme-linked immunosorbent assay. Data analysis was performed using R statistical software. The predominant malaria vector was An. funestus sensu lato (s.l.), which had an overall dye feeding rate of 11.2%. This was followed by An. gambiae s.l. at 3.5%. These corresponded to daily feeding rates of 4.8% and 1.2%, respectively. Sporozoite positivity rates were 2.3% (n = 29) in An. funestus s.l and 1.0% (n = 19) in An. gambiae s.l. Higher dye positivity was observed in male An. funestus (OR = 1.22; 95% CI = 1.03,1.46; P = 0.029) and male An. gambiae (OR = 2.20; 95% CI = 1.19,4.08; P = 0.015). Comparison of the impact of 2 versus 3 bait stations indicated no difference in feeding rates in either An. funestus (OR = 0.83; 95% CI = 0.40; 1.75), P = 0.624) or An. gambiae (OR = 1.11; 95% CI = 0.71, 1.71; P = 0.661). The results from this study showed that predominant malaria vectors; Anopheles funestus led to a daily feeding rate that was presumed to be sufficient to cause a reduction in malaria incidence by ATSBs. There was no significant difference detected between deploying two or three bait stations per structure. The study provided important information utilized in the subsequent deployment of ATSBs in epidemiological trials.

Background Attractive targeted sugar bait (ATSB) stations are a promising new approach to malaria vector control that could compliment current tools by exploiting the natural sugar feeding behaviors of mosquitoes. Recent proof of concept work with a prototype ATSB ® Sarabi Bait Station (Westham Co., Hod-Hasharon, Israel) has demonstrated high feeding rates and significant reductions in vector density, human biting rate, and overall entomological inoculation rate for Anopheles gambiae sensu lato ( s.l.) in the tropical savannah of western Mali. The study reported here was conducted in the more temperate, rainier region of Western Province, Zambia and was designed to confirm the primary vector species in region and to estimate corresponding rates of feeding from prototype attractive sugar bait (ASB) Sarabi Bait Stations. Methods The product evaluated was the Sarabi v1.1.1 ASB station, which did not include insecticide but did include 0.8% uranine as a dye allowing for the detection, using UV fluorescence light microscopy, of mosquitoes that have acquired a sugar meal from the ASB. A two-phase, crossover study design was conducted in 10 village-based clusters in Western Province, Zambia. One study arm initially received 2 ASB stations per eligible structure while the other initially received 3. Primary mosquito sampling occurred via indoor and outdoor CDC Miniature UV Light Trap collection from March 01 through April 09, 2021 (Phase 1) and from April 19 to May 28, 2021 (Phase 2). Results The dominant vector in the study area is Anopheles funestus s.l., which was the most abundant species group collected (31% of all Anophelines; 45,038/144,5550), had the highest sporozoite rate (3.16%; 66 positives out of 2,090 tested), and accounted for 94.3% (66/70) of all sporozoite positive specimens. Of those An. funestus specimens further identified to species, 97.2% (2,090/2,150) were An. funestus sensu stricto ( s.s .). Anopheles gambiae s.l. (96.8% of which were Anopheles arabiensis ) is a likely secondary vector and Anopheles squamosus may play a minor role in transmission. Overall, 21.6% (9,218/42,587) of An. funestus specimens and 10.4% (201/1,940) of An. gambiae specimens collected were positive for uranine, translating into an estimated daily feeding rate of 8.9% [7.7–9.9%] for An. funestus (inter-cluster range of 5.5% to 12.7%) and 3.9% [3.3–4.7%] for An. gambiae (inter-cluster range of 1.0–5.2%). Feeding rates were no different among mosquitoes collected indoors or outdoors, or among mosquitoes from clusters with 2 or 3 ASBs per eligible structure. Similarly, there were no correlations observed between feeding rates and the average number of ASB stations per hectare or with weekly rainfall amounts. Conclusions Anopheles funestus and An. gambiae vector populations in Western Province, Zambia readily fed from the prototype Sarabi v1.1.1 ASB sugar bait station. Observed feeding rates are in line with those thought to be required for ATSB stations to achieve reductions in malaria transmission when used in combination with conventional control methods (IRS or LLIN). These results supported the decision to implement a large-scale, epidemiological cluster randomized controlled trial of ATSB in Zambia, deploying 2 ATSB stations per eligible structure.

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.

Background 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). Methods 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. Results 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. Conclusion 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.

Background Attractive targeted sugar baits (ATSBs) are a potential addition to an integrated vector management strategy against malaria. ATSB stations, which include a sugar bait and an ingestion toxicant, could potentially be deployed to attract-and-kill mosquitoes and thereby prevent malaria transmission. The physical durability of these stations is likely to be an important factor in decisions around future use strategies. This study measured the duration of physical integrity of the ATSB Sarabi v1.2 stations used in Western Zambia, as part of a Phase III cluster RCT. Methods ATSB stations were installed and followed as a cohort on the external walls of selected sleeping structures in households in trial clusters (10–11 per cluster). Monthly visits were made to assess the presence and condition of the ATSBs from November 2022 to June 2023. A rolling cohort approach was used, whereby new ATSB stations were used to replace those which failed or were lost-to-follow-up, and these were subsequently enrolled in the cohort. Information on structure construction and ATSBs location on the walls was also collected. Median ATSB survival and associated factors were analysed with Kaplan–Meier curves and Cox-Proportional hazard models. Results Including replacements, a total of 1107 ATSBs were installed across 304 sleeping structures in 206 households, and 5696 ATSB-visits were made. Common types of damage observed were holes/tears, mold, and leakage of bait. While the median survival time for the devices was 5 months (149 days) for all stations in the study, the median survival time was longer than the transmission season for stations installed in locations well protected by the roof (> 218 days). ATSB station survival was longer when installed on structures with thatched roofs compared to iron-sheet roofs (HR 0.37, 95% CI 0.26–0.47, p < 0.001), and where there was “excellent protection” (HR = 0.36, 95% CI 0.25–0.49, p < 0.001), compared to “no protection”. Conclusions Study results suggest that the majority of ATSB stations deployed in this setting will remain intact for a 7-month seasonal deployment period if stations are installed in locations protected from weather elements, such as underneath the overhang of thatched roof. Further research is needed to understand factors that influence the physical integrity and efficacy of ATSB stations in addition to those observed in this study.

Background Attractive Targeted Sugar Baits (ATSBs) offer a complementary vector control strategy to interventions targeting blood feeding or larval control by attacking the sugar feeding behaviour of adult mosquitoes using an attract-and-kill approach. Western Zambia was the first location to receive and deploy ATSB Sarabi version 1.2 stations in a Phase III cluster randomized controlled trial. This paper describes ATSB station installation, monitoring, removal, and disposal, quantifies ATSB station coverage, and reports major reasons for ATSB station replacement. Methods ATSB stations were deployed during two annual transmission seasons, through scheduled installation and removal campaigns. During deployment, monitoring was conducted per protocol to maintain high coverage of the ATSB stations in good condition. Routine monitoring visits during the trial captured details on ATSB station damage necessitating replacement following pre-defined replacement criteria. Annual cross-sectional household surveys measured ATSB station coverage during peak malaria transmission. Results A total of 67,945 ATSB stations were installed in Year 1 (41,695 initially installed+ 26,250 installed during monitoring) and 69,494 ATSB stations were installed in Year 2 (41,982 initially installed+ 27,512 installed during monitoring) across 35 intervention clusters to maintain high coverage of two ATSB stations in good condition per eligible household structure. The primary reasons for ATSB station replacement due to damage were holes/tears and presence of mold. Cross-sectional household surveys documented high coverage of ATSB stations across Year 1 and Year 2 with 93.1% of eligible structures having ≥ 2 ATSB stations in any condition. Discussion ATSB station deployment and monitoring efforts were conducted in the context of a controlled cRCT to assess potential product efficacy. Damage to ATSB stations during deployment required replacement of a subset of stations. High coverage of eligible structures was maintained over the two-year study despite replacement requirements. Additional research is needed to better understand the impact of damage on ATSB station effectiveness under programmatic conditions, including thresholds of threats to physical integrity and biological deterioration on product efficacy. Conclusions Optimizing ATSB stations to address causes of damage and conducting implementation research to inform optimal delivery and cost-effective deployment will be important to facilitate scale-up of ATSB interventions.

Mass-release of sterile male mosquitoes is a promising option for controlling dengue and malaria, but it has never been shown that lab-raised transgenic males can compete effectively with their wild counterparts outside laboratory conditions. Promising results from a restricted field trail now suggest the feasibility of extending the approach for large-scale mosquito-control programs. Dengue is the most medically important arthropod-borne viral disease, with 50–100 million cases reported annually worldwide 1 . As no licensed vaccine or dedicated therapy exists for dengue, the most promising strategies to control the disease involve targeting the predominant mosquito vector, Aedes aegypti . However, the current methods to do this are inadequate. Various approaches involving genetically engineered mosquitoes have been proposed 2 , 3 , 4 , including the release of transgenic sterile males 5 , 6 , 7 , 8 , 9 , 10 . However, the ability of laboratory-reared, engineered male mosquitoes to effectively compete with wild males in terms of finding and mating with wild females, which is critical to the success of these strategies, has remained untested. We report data from the first open-field trial involving a strain of engineered mosquito. We demonstrated that genetically modified male mosquitoes, released across 10 hectares for a 4-week period, mated successfully with wild females and fertilized their eggs. These findings suggest the feasibility of this technology to control dengue by suppressing field populations of A. aegypti .

BACKGROUND: Control of the world’s most important vector-borne viral disease, dengue, is a high priority. A lack of vaccines or effective vector control methods means that novel solutions to disease control are essential. The release of male insects carrying a dominant lethal (RIDL) is one such approach that could be employed to control Aedes aegypti. To maximise the potential of RIDL control, optimum release strategies for transgenic mosquitoes are needed. The use of field data to parameterise models allowing comparisons of the release of different life-stages is presented together with recommendations for effective long-term suppression of a wild Ae. aegypti population. METHODS: A compartmental, deterministic model was designed and fitted to data from large-scale pupal mark release recapture (MRR) field experiments to determine the dynamics of a pupal release. Pulsed releases of adults, pupae or a combination of the two were simulated. The relative ability of different release methods to suppress a simulated wild population was examined and methods to maintain long-term suppression of a population explored. RESULTS: The pupal model produced a good fit to field data from pupal MRR experiments. Simulations using this model indicated that adult-only releases outperform pupal-only or combined releases when releases are frequent. When releases were less frequent pupal-only or combined releases were a more effective method of distributing the insects. The rate at which pupae eclose and emerge from release devices had a large influence on the relative efficacy of pupal releases. The combined release approach allows long-term suppression to be maintained with smaller low-frequency releases than adult- or pupal-only release methods. CONCLUSIONS: Maximising the public health benefits of RIDL-based vector control will involve optimising all stages of the control programme. The release strategy can profoundly affect the outcome of a control effort. Adult-only, pupal-only and combined releases all have relative advantages in certain situations. This study successfully integrates field data with mathematical models to provide insight into which release strategies are best suited to different scenarios. Recommendations on effective approaches to achieve long-term suppression of a wild population using combined releases of adults and pupae are provided.