Community evaluation of VECTRON™ T500 (broflanilide) for indoor residual spraying for malaria vector control in Siaya county, Kenya

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Wekesa, Brian Polo, Margaret Muchoki, Seline Omondi, and 11 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7021640/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 29 Nov, 2025 Read the published version in Malaria Journal → Version 1 posted 10 You are reading this latest preprint version Abstract Background Indoor residual spraying (IRS) remains a core malaria vector control intervention, but widespread insecticide resistance threatens its effectiveness. VECTRON™ T500, containing broflanilide, represents a novel IRS product with a new mode of action targeting GABA receptors. Methods A two-arm non-inferiority study was conducted in Bar Olengo, Siaya County, Kenya, between June and November 2024. Twenty-five structures per arm were sprayed with either VECTRON™ T500 (100mg a.i/m²) or Actellic™ 300CS (1g a.i/m²), with five water-sprayed controls. Residual efficacy was assessed using WHO cone bioassays with pyrethroid-resistant Anopheles gambiae s.s. Bungoma strain and susceptible Kisumu strain monthly for six months. Wild vector susceptibility to insecticides, community acceptability, and adverse events were evaluated. Results VECTRON™ T500 maintained significantly higher mortality than Actellic™ 300CS throughout six months on both wall types. Against resistant An. gambiae s.s. Bungoma strain, VECTRON™ T500 achieved 98.73 ± 3.51% mortality (95% CI: 97.95–99.51%) compared to 80.22 ± 11.23% for Actellic™ 300CS (95% CI: 77.72–82.72%; t₇₈=-10.15, p < 0.001, Cohen's d = 2.27). For susceptible Kisumu strain, VECTRON™ T500 maintained 100% mortality versus 89.60 ± 6.34% for Actellic™ 300CS (95% CI: 88.19–91.01%; t₇₈=10.53, p 95% effective throughout. Wild An. gambiae s.l. and An. funestus s.l. showed 100% susceptibility to broflanilide with no cross-resistance detected. No adverse events occurred in VECTRON™ T500 households versus 8% (12/150) in Actellic™ 300CS households. Community acceptance was 100% for VECTRON™ T500 versus 99.33% (149/150) for Actellic™ 300CS. Conclusions VECTRON™ T500 demonstrated superior residual efficacy, excellent safety profile, and high community acceptance compared to Actellic™ 300CS. Its novel mode of action and absence of cross-resistance make it valuable for insecticide resistance management in malaria vector control programs. Indoor residual spraying broflanilide insecticide resistance malaria vector control Anopheles gambiae Kenya Figures Figure 1 Figure 2 Figure 3 Figure 4 Background Vector control has significantly reduced malaria transmission across endemic regions with varying epidemiological conditions [ 1 ]. Indoor residual spraying (IRS), involving treatment of interior house surfaces with residual insecticide formulations, remains a core intervention as demonstrated during the global malaria eradication program [ 2 ]. According to WHO reports, IRS protected approximately 1.6% of at-risk populations globally in malaria endemic countries with 88.4% coverage of target structures [ 3 ]. IRS targets adult mosquitoes feeding indoors (endophagic) and resting indoors (endophilic) through repellency effects or by killing them when they contact treated surfaces with lethal insecticide concentrations [ 4 ]. Massive vector population declines and reduced longevity from IRS effectively reduce malaria transmission through decreased vectorial capacity [ 5 ]. Sustainable IRS implementation has substantially impacted malaria prevalence globally, especially in high transmission areas [ 6 ]. WHO-recommended insecticide classes for IRS include pyrethroids, organochlorines, carbamates, organophosphates, neonicotinoids, and pyrroles [ 7 ]. Prolonged reliance on single insecticide classes increases resistance, reducing IRS efficacy [ 8 ]. Resistance to organophosphates, pyrethroids, carbamates, and organochlorines has been reported globally with varying intensities across WHO regions [ 9 ]. To mitigate resistance development, WHO recommends four strategies (mixtures, rotations, mosaics, and combinations) to preserve vector susceptibility [ 10 ]. Available insecticidal products are insufficient to meet growing malaria vector control challenges due to limited alternative insecticides [ 11 ]. Consistent innovation of new products that overcome resistance, have longer residual effects, and maintain efficacy in high transmission areas continues [ 11 ]. Conventional IRS insecticides display two major biochemical modes of action: sodium channel disruption (pyrethroids and organochlorines) and acetylcholinesterase inhibition (organophosphates and carbamates) [ 12 ]. Next-generation insecticides include chlorfenapyr (pyrrole class) with distinctive oxidative phosphorylation uncoupling in insect mitochondria [ 13 ], neonicotinoids like clothianidin acting through nicotinic acetylcholine receptor overstimulation [ 14 ], indoxacarb blocking sodium ion channels, and insect growth regulators disrupting development through juvenile hormone mimicking or inhibition [ 12 , 6 ]. VECTRON™ T500, a wettable powder formulation containing broflanilide produced by Mitsui Chemicals Crop & Life Solutions, Inc. (MCCLS), is among the most recently WHO-prequalified IRS insecticides [ 15 ]. Broflanilide contains a meta-diamide chemical structure offering a novel mode of action against malaria vectors compared to existing IRS insecticide classes [ 16 ]. It functions by inhibiting neurotransmission through non-competitive antagonism of γ-aminobutyric acid (GABA) receptors on chloride-gated channels, causing hyperexcitation, convulsion, and death [ 12 , 16 ]. Meta-diamides and isoxazolines (Group 30 insecticides - GABA-gated chloride channel allosteric modulators) are characterized by long residual activity and effectiveness against pyrethroid-resistant insects on different substrates [ 17 ]. Broflanilide's novel GABA receptor targeting provides significant resistance management advantages, representing a distinctive class creating opportunities for effective rotation strategies [ 12 , 16 ]. This unique mechanism may explain the absence of cross-resistance with existing resistance mechanisms in African malaria vectors [ 18 , 19 ]. Comparing VECTRON™ T500 with Actellic™ 300CS (pirimiphos-methyl) is particularly relevant as the latter represents the first-in-class organophosphate widely deployed for IRS in Kenya since 2017 following widespread pyrethroid resistance development [ 20 ]. This study, required by Kenya's Pest Control Products Board (PCPB) for VECTRON™ T500 registration, evaluated residual efficacy compared to Actellic™ 300CS on pyrethroid-resistant and susceptible An. gambiae s.s. strains, with secondary endpoints including community acceptability and safety. Methods Study Area This study was conducted in Bar Olengo location (-0.0728262°N, 34.6699246°E), Bondo sub-county, Siaya County, Kenya. Siaya County, located in western Kenya and bordered by Lake Victoria, provides favorable mosquito breeding environments. The county has high malaria prevalence, ranking second nationally [ 21 , 22 ]. Current vector control relies solely on pyrethroid-only insecticide-treated nets (ITNs). The area receives 800-2000mm annual bimodal rainfall with 60–80% humidity. Annual mean temperatures range 30–35°C, favoring malaria vector survival and breeding [ 23 ]. Principal vectors are An. funestus s.s., An. gambiae s.s., and An. arabiensis , all exhibiting high-intensity pyrethroid resistance. Main economic activities include fishing, rice farming, livestock raising, small-scale trading, and gold mining. Study Design and Randomization A longitudinal two-arm evaluation study was conducted between June and November 2024. The study area was stratified by village (Waga and Bungu), then by wall type (mud and cement) to ensure balanced representation. Using computer-generated random numbers, 25 eligible structures from each village were selected with equal wall type allocation. VECTRON™ T500 was applied in Waga village while Actellic™ 300CS was applied in Bungu village, with 5 randomly selected structures per village serving as negative controls (water-sprayed). Sample Size Calculation Based on previous IRS efficacy studies and assuming 90% mortality for the control product with 80% power to detect a 10% difference at 5% significance level, 25 structures per arm provided adequate power for non-inferiority testing. Test Products and Application VECTRON™ T500 Wettable powder containing 50% broflanilide active ingredient, supplied in 50g sachets and applied at 100mg a.i/m². Full safety information, toxicological reports, and certificates of analysis were provided by MCCLS. Actellic™ 300CS Pirimiphos-methyl applied at 1g a.i/m² as positive control. Residual Efficacy Assessment WHO cone bioassays followed standard guidelines [ 24 ] at 7 days post-spraying for quality assessment, then monthly for six months evaluating residual efficacy. Ten households per village were randomly selected, stratified by wall type (5 mud, 5 cement). Cone bioassays used 2-5-day-old non-blood-fed females from two laboratory colonies: Pyrethroid-resistant An. gambiae s.s. Bungoma strain (elevated P450 enzymes, Ace-1 mutations, kdr polymorphisms) Susceptible An. gambiae s.s. Kisumu strain Bioassays were conducted at three heights (0.5, 1.0, 1.5 meters) on different walls per room. Two cones per test point exposed 10 mosquitoes each for 30 minutes. Mosquitoes were aspirated into labeled cups; knockdown was recorded at 60 minutes, mortality monitored at 24, 48, and 72 hours under controlled conditions (27 ± 2°C, 80 ± 10% relative humidity). Control assays on unsprayed surfaces applied Abbott's formula when control mortality exceeded 5% but remained below 20%. Assays with > 20% control mortality were repeated. Wild Vector Susceptibility Testing Comprehensive bioassays established insecticide resistance status. An. gambiae s.l. larvae were collected from multiple breeding sites before spraying and reared to adulthood. Blood-fed adult An. funestus were collected using mouth aspirators for F₀ generation testing. Standard WHO tube bioassays used diagnostic concentrations: deltamethrin (0.05%), permethrin (0.75%), alpha-cypermethrin (0.05%), and pirimiphos-methyl (0.25%). Resistance intensity bioassays used 5× and 10× diagnostic concentrations. Synergist assays exposed mosquitoes to 4% piperonyl butoxide (PBO) for 1 hour before pyrethroid exposure. CDC bottle bioassays for broflanilide and pirimiphos-methyl followed established methods [ 25 ] with discriminating concentrations: 6 µg/bottle with 800 ppm Mero adjuvant for broflanilide and 20 µg/bottle for pirimiphos-methyl. Knockdown was recorded at 60 minutes, mortality at 24 hours for pyrethroids and pirimiphos-methyl, 48 hours for broflanilide. Four replicates with 20–25 unfed mosquitoes per replicate were used per insecticide. Molecular assays identified An. gambiae complex [ 26 ] and An. funestus complex [ 27 ] species. Resistance status classification followed WHO criteria: ≥98% mortality (susceptible), 90–97% (possible resistance), < 90% (confirmed resistance). Community Acceptability and Adverse Events Baseline questionnaires captured pre-intervention health status. Questionnaires were administered to household heads on spraying day, one week post-spraying, and monthly for six months, determining factors influencing VECTRON™ T500 acceptability compared to Actellic™ 300CS. User acceptability was calculated as the ratio of household refusals to total structures sprayed, recording refusal reasons. Three months post-intervention, 20 audio-recorded in-depth interviews assessed product acceptability among end-users and spray operators. Eight households per arm were randomly interviewed, evenly split between wall types. Four spray operators familiar with both products explored knowledge, perceptions, and experiences. Apparently healthy sprayers were enrolled after pre-spray questionnaire screening. Daily post-spray questionnaires captured adverse events experienced during and after spraying. Household heads received adverse events questionnaires for six months in both intervention areas and controls. Both sprayers and householders were encouraged to report suspected insecticide-related symptoms immediately. Statistical Analysis Data collection used CommCare™ application with structured questionnaires. Residual efficacy analysis calculated mortality means from both arms and negative controls. Independent t-tests determined mortality differences with effect sizes calculated using Cohen's d. Control mortality > 5% was adjusted using Abbott's formula. Susceptibility test data analyzed mortality means from each insecticide tested. Community acceptability was calculated as mean household refusals to total sprayed structures, analyzed using independent t-tests. In-depth interview audio records were transcribed and coded using NVivo version 14. Codebook-guided initial deductive coding while inductive coding captured emerging themes. Thematic synthesis identified patterns across codes and respondent categories. Adverse events were calculated by finding means of reported symptoms and analyzed using independent t-tests. Statistical analysis and visualization used R version 4.4.0. Ethical and Regulatory Considerations This study was conducted under PCPB trial permit PCPB/Eval/Vol.I/24/44. The protocol was approved by Kenya Medical Research Institute's Scientific and Ethics Review Unit (SERU 4536). Community consent was obtained from Siaya County health department, local chiefs, village leaders, and community health promoters. Written informed consent was obtained from household heads and sprayers. Results Residual Efficacy VECTRON™ T500 consistently maintained higher mortality than Actellic™ 300CS throughout the six-month period on both wall surfaces. For resistant An. gambiae s.s. Bungoma strain, VECTRON™ T500 induced 98.73 ± 3.51% mortality compared to 80.22 ± 11.23% for Actellic™ 300CS (t₇₈=-10.15, p < 0.001, Cohen's d = 2.27) (Fig. 1 ). For susceptible An. gambiae s.s. Kisumu strain, VECTRON™ T500 maintained 100% mortality versus 89.60 ± 6.34% for Actellic™ 300CS (t₇₈=10.53, p < 0.001, Cohen's d = 2.38) (Fig. 2 ). Critically, Actellic™ 300CS efficacy declined below the WHO-recommended 80% threshold after month 4 for resistant mosquitoes, dropping to 76.2% in month 5 and 71.8% in month 6. VECTRON™ T500 maintained > 95% mortality throughout the entire evaluation period, never falling below 96.5% for any strain or time point (Table 1 ). Table 1 Monthly mortality rates (mean ± standard deviation) of pyrethroid-resistant An. gambiae s.s. Bungoma strain and susceptible An. gambiae s.s. Kisumu strain following exposure to VECTRON™ T500 (100 mg a.i./m²) and Actellic™ 300CS (1000 mg a.i./m²) treated surfaces in WHO cone bioassays over six months post-application. Mortality was assessed at 72 hours post-exposure. Control mortality > 5% was corrected using Abbott's formula. WHO efficacy threshold for IRS products is ≥ 80% mortality. Month VECTRON™ T500 Actellic™ 300CS Resistant (%) Susceptible (%) Resistant (%) Susceptible (%) 1 100.0 ± 0.0 100.0 ± 0.0 92.3 ± 4.2 96.8 ± 2.1 2 99.2 ± 1.8 100.0 ± 0.0 88.7 ± 6.8 94.2 ± 3.6 3 98.9 ± 2.1 100.0 ± 0.0 85.4 ± 8.1 91.5 ± 4.8 4 98.1 ± 2.8 100.0 ± 0.0 79.8 ± 9.2 88.7 ± 5.2 5 97.8 ± 3.2 100.0 ± 0.0 76.2 ± 11.4 85.3 ± 6.8 6 96.5 ± 3.9 100.0 ± 0.0 71.8 ± 12.6 82.1 ± 7.4 Residual efficacy of the IRS products on different wall types Mortality means for resistant An. gambiae s.s. Bungoma strain were higher with VECTRON™ T500 on both cement (98.66 ± 3.56%) and mud (100%) walls compared to Actellic™ 300CS on cement (78.82 ± 15.57%) and mud (77.75 ± 11.69%) walls. Statistically significant differences existed for cement walls (t₁₂=3.286, p = 0.007) and mud walls (t₁₂=5.037, p < 0.001). Mortality was observed to fall below 80% at month 4 in the Actellic™ 300CS arm (Fig. 3 ). For susceptible An. gambiae s.s. Kisumu strain, VECTRON™ T500 maintained 100% mortality on both wall types compared to Actellic™ 300CS cement (88.01 ± 8.5%) and mud (86.65 ± 6.64%) performance. Significant differences were observed for cement (t₁₂=3.700, p = 0.003) and mud (t₁₂=5.318, p < 0.001) walls (Fig. 3 ). Susceptibility of wild Anopheles mosquitoes to Broflanilide and pirimiphos methyl Among 2,400 wild vectors tested, molecular identification of 400 specimens revealed: 200 An. funestus s.l. (98% An. funestus s.s., 2% An. leesoni ), 200 An. gambiae s.l. consisting 92% An. arabiensis , and 2% An. gambiae s.s, the rest were unamplified. CDC bottle bioassays showed Broflanilide induced 100% mortality in both An. gambiae s.l. and An. funestus s.l. with delayed mortality at 48 hours, indicating no cross-resistance detection. Pirimiphos-methyl similarly induced 100% mortality at 24 hours post-exposure (Fig. 4 , Table 2 ). Table 2 Susceptibility of field-collected An. gambiae s.l. and An. funestus s.l. to broflanilide, pirimiphos-methyl, and deltamethrin determined using WHO bottle bioassays and CDC bottle bioassays. Mosquitoes were exposed to diagnostic concentrations: broflanilide (6 µg/bottle with 800 ppm Mero adjuvant), pirimiphos-methyl (20 µg/bottle), and deltamethrin (12.5 µg/bottle). Piperonyl butoxide (PBO) synergist assays used 4% PBO pre-exposure for 1 hour before deltamethrin exposure. Mortality was recorded at 24 hours for deltamethrin and pirimiphos-methyl, and 48 hours for broflanilide. Resistance status classification follows WHO criteria: ≥98% mortality (susceptible), 90–97% (possible resistance), < 90% (confirmed resistance). Data represent mean percentage mortality ± standard deviation with 95% confidence intervals. Species Insecticide Mortality (%) 95% CI Status An. gambiae s.l. Broflanilide 100 100.0-100.0 Susceptible An. funestus s.l. Broflanilide 100 100.0-100.0 Susceptible An. gambiae s.l. Pirimiphos-methyl 100 100.0-100.0 Susceptible An. funestus s.l. Pirimiphos-methyl 100 100.0-100.0 Susceptible An. gambiae s.l. Deltamethrin 23.4 ± 8.2 19.8–27.0 Resistant An. funestus s.l. Deltamethrin 31.2 ± 9.6 26.4–36.0 Resistant An. gambiae s.l. Deltamethrin + PBO 100.0 ± 0.0 100.0-100.0 Susceptible An. funestus s.l. Deltamethrin + PBO 89.3 ± 6.4 85.1–93.5 Resistant Wild vector pyrethroid mortality fell below WHO resistance thresholds. PBO pre-exposure restored susceptibility to some pyrethroids, with full susceptibility only to deltamethrin (100 ± 0%) and possible resistance to alpha-cypermethrin (97 ± 3.83%) in An. gambiae s.l. Significant mortality differences existed between An. gambiae s.l. and An. funestus (t₂=-5.52, p = 0.03) (Table 2 ). Adverse Events and Safety Throughout six months, 150 responses per intervention arm and five from negative controls were recorded. No adverse events were reported from VECTRON™ T500 households (0/150), while Actellic™ 300CS households reported adverse events in 8% of cases (12/150). Reported events included skin itchiness, facial burning, sneezing, eye irritation, and bad smell. Skin and facial burning was most frequent (2.7%, 4/150). Most adverse events occurred from spraying day to one-month post-spraying; none were reported after month 2. Community Acceptability No statistically significant difference existed in future acceptability between VECTRON™ T500 (10.24%±12.25) and Actellic™ 300CS (9.16%±12.44) (t₃₄=0.188, p = 0.852). Main VECTRON™ T500 acceptance factors were malaria reduction ability (48%, 72/150) and mosquito killing (31%, 47/150). For Actellic™ 300CS, malaria reduction was the primary reason (37%, 56/150). No refusals occurred in VECTRON™ T500 households throughout evaluation. Actellic™ 300CS had 4% refusal (1/25), attributed to insecticide odor. Most participants from both wall types expressed willingness for future VECTRON™ T500 spraying due to mosquito reduction. Discussion The high residual efficacy of VECTRON™ T500, maintaining > 95% mortality throughout six months against both susceptible and resistant An. gambiae s.s. mosquitoes, represents compelling evidence for its potential in western Kenya's high-resistance contexts. The consistent performance across wall types addresses a critical operational challenge, as mud surfaces often present alkaline pH and porosity that can degrade or sequester active ingredients [ 28 , 29 ]. The findings are consistent with recent experimental hut studies conducted in Benin [ 30 , 31 ] and Tanzania [ 32 , 33 ], which demonstrated prolonged efficacy of VECTRON™ T500 against pyrethroid-resistant An. gambiae s.l. populations. The extended efficacy duration has significant programmatic implications. While Actellic™ 300CS would require reapplication after 4 months to maintain WHO-recommended efficacy thresholds in this context, VECTRON™ T500's sustained performance suggests potential for extended spray cycles. This could reduce operational costs, logistical demands, and household disruption while maintaining protection levels. Similar extended residual activity has been reported in experimental hut studies in Benin, where cone bioassay mortality remained > 80% for 18 months [ 30 ], and in Tanzania where efficacy persisted for 12 months [ 32 ]. Community trials in Benin demonstrated that VECTRON™ T500 maintained 100% mortality in wall cone bioassays for 24 months on both cement and mud walls [ 34 ]. Cost-effectiveness modelling based on these efficacy data would be valuable for program planning. Assuming similar application costs, the extended efficacy could translate to substantial savings through reduced spray frequencies. However, formal economic evaluation incorporating product costs, application expenses, and health outcomes is needed to quantify potential savings. This study represents the first comprehensive field evaluation of VECTRON™ T500 against An. funestus s.l. populations. Previous evaluations have primarily focused on An. gambiae s.l. and An. arabiensis populations [ 30 – 33 ], with An. funestus either absent from study sites or present in insufficient numbers for meaningful analysis. A recent multi-centre discriminating concentration study specifically noted that "unfortunately, this was not feasible for inclusion... due to notorious difficulties rearing this particular species under controlled insectary conditions" [ 35 ]. The complete susceptibility of wild An. funestus s.l. to broflanilide (100% mortality at 6 µg/bottle) documented in this study is particularly significant given the critical role this species plays in malaria transmission across eastern and southern Africa [ 36 , 37 ], making the efficacy of VECTRON™ T500 against this species particularly valuable for elimination efforts. The GABA receptor targeting mechanism differs fundamentally from existing insecticide classes, providing genuine rotation options for sustainable resistance management [ 16 , 38 ]. This finding aligns with previous laboratory and field studies that demonstrated no cross-resistance between broflanilide and pyrethroid resistance mechanisms in Burkina Faso, Benin, Tanzania[ 30 , 32 , 33 , 39 , 41 ], and now Kenya, suggesting broad applicability for resistance management across diverse vector populations. The absence of adverse events in VECTRON™ T500 households versus 8% in Actellic™ 300CS households, combined with 100% community acceptance, addresses critical implementation barriers. High refusal rates can compromise IRS coverage and effectiveness [ 42 , 43 ]. The superior acceptability profile suggests VECTRON™ T500 could achieve better coverage in operational settings. This safety profile is consistent with findings from community trials in Benin [ 34 ] and Burkina Faso [ 41 ], where minimal to no adverse events were reported with VECTRON™ T500. The primary acceptance drivers (malaria reduction and mosquito killing effectiveness) align with actual product performance, indicating realistic community perceptions. This concordance between expectations and performance suggests sustainable acceptance in repeated spray cycles, as demonstrated in the Burkina Faso study where acceptance remained high throughout a 12-month evaluation period [ 41 ]. The performance of VECTRON™ T500 compares favorably with other recently developed IRS formulations. Experimental hut studies comparing VECTRON™ T500 with Actellic™ 300CS in Benin showed non-inferiority in terms of mosquito mortality, with VECTRON™ T500 demonstrating superior residual activity [ 30 ]. Similarly, community trials comparing VECTRON™ T500 with Fludora® Fusion in both Benin [ 34 ] and Tanzania [ 44 ] demonstrated non-inferiority in reducing vector densities while showing extended residual efficacy. The delayed mortality characteristic of VECTRON™ T500, attributed to its requirement for metabolic activation to desmethyl-broflanilide [ 45 ], has been observed consistently across studies. While this differs from the rapid knockdown effects of pyrethroids, modelling studies suggest that such slower-acting insecticides may be less likely to select for resistance [ 46 ], potentially extending their operational lifespan. Several limitations warrant consideration. The six-month evaluation period, while comprehensive for regulatory purposes, may not capture long-term resistance development or efficacy decline. Extended monitoring would strengthen evidence for operational decision-making. Recent studies in Benin and Tanzania with longer follow-up periods (18–24 months) have shown sustained efficacy [ 30 , 34 ], suggesting that the performance observed in this study would likely continue beyond six months. The study design used village-level allocation rather than household randomization, potentially introducing geographical confounding. However, the stratification by wall type and similar baseline characteristics minimize this risk. Cost-effectiveness analysis was beyond this study's scope but represents a critical knowledge gap for program planning. The superior efficacy must be balanced against potential cost differences for informed product selection. Seasonal variations in efficacy were not fully captured given the June-November study period. Year-round evaluation would provide more comprehensive efficacy profiles under varying environmental conditions, as demonstrated in the Burkina Faso study which showed consistent performance across both dry and wet seasons [ 41 ]. Conclusions VECTRON™ T500 demonstrated superior residual efficacy compared to Actellic™ 300CS, maintaining > 95% mortality throughout six months against both susceptible and pyrethroid-resistant An. gambiae s.s. strains. Importantly, this study provides the first comprehensive field evidence of VECTRON™ T500's efficacy against An. funestus s.l., showing complete susceptibility with no cross-resistance. The excellent safety profile with zero adverse events and 100% community acceptance collectively position VECTRON™ T500 as a valuable tool for malaria vector control programs. The novel GABA receptor targeting mode of action provides genuine resistance management options, while extended residual activity offers potential operational advantages through reduced application frequency. These characteristics align with WHO Global Plan for Insecticide Resistance Management recommendations emphasizing rotation between insecticides with different modes of action [ 10 ]. The findings support incorporating VECTRON™ T500 into resistance management strategies for sustainable malaria vector control, particularly in areas with high pyrethroid resistance or where An. funestus s.l. contributes significantly to transmission. The superior performance profile, combined with evidence from other African settings, warrants consideration for national malaria control program adoption, pending cost-effectiveness evaluation and regulatory approval. Abbreviations °C Degree Celsius µg Microgram Ace 1-Acetylcholinesterase 1 AI Active Ingredient; a.i/m²-Active ingredient per square meter An. Anopheles CDC Centers for Disease Control CFV Control Flow Valve CGHR Centre for Global Health Research CHPs Community Health Promoters CI Confidence Interval F₀ Parent generation GABA Gamma-aminobutyric acid IDI In-depth interview IGRs Insect Growth Regulators IRAC Insecticide Resistance Action Committee IRS Indoor Residual Spraying IVCC Innovative Vector Control Consortium kdr Knockdown resistance KEMRI Kenya Medical Research Institute MCCLS Mitsui Chemicals Crop & Life Solutions Inc nAChR Nicotinic acetylcholine receptors PBO Piperonyl butoxide; PCPB-Pest Control Products Board PPE Personal Protective Equipment s.l. sensu lato; s.s.-sensu stricto WHO World Health Organization Declarations Ethics Approval and Consent to Participate The study protocol was approved by Kenya Medical Research Institute's Scientific and Ethics Review Unit (SERU 4536). Written informed consent was obtained from all participants. Consent for Publication Not applicable. Competing Interests The authors declare no competing interests. Funding This study was funded by Mitsui Chemicals Crop & Life Solutions, Inc. (MCCLS: Tokyo, Japan). The funder provided test materials and funding but was not involved in study design, data collection, analysis, or manuscript preparation. Author Contribution EO, ER, BA, IA, PK, PM, KK, CW, MM, BP designed and implemented the study. MM, BP, EO mapped the study area and provided data collection tools. EO, ER, BA, IA, PK, PM, KK, CW, MM, BP supervised spray operations and ensured environmental compliance. BP and CW coordinated study activities including entomological surveys, bioassays, resistance monitoring, data analysis, and visualization. MK performed susceptibility assays. CW performed molecular assays for mosquito speciation. CW wrote the manuscript with assistance from EO and BP. TB and CW conducted adverse events and acceptability surveys. EO, BP, DS, SO, TB, and MGM reviewed the manuscript. All authors read and approved the final manuscript. Acknowledgement The authors thank Mitsui Chemicals Crop & Life Solutions, Inc. for providing test materials with full safety information, toxicological reports, and certificates of analysis. We acknowledge MCCLS and IVCC teams for manuscript review support. We thank Siaya County malaria control coordination team and Bar Olengo local administration for their support. We appreciate household owners for allowing structure enrollment and KEMRI/CGHR Entomology department technical staff for mosquito provision, bioassay testing, and molecular assays. We acknowledge the Pest Control Products Board, Ministry of Agriculture, for evaluation oversight. Availability of Data and Materials The data sets supporting the conclusion of this study is available within the article. Raw datasets are available from the corresponding authors on reasonable request. References Bhatt S, Weiss DJ, Cameron E, Bisanzio D, Mappin B, Dalrymple U, et al. 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Geneva: World Health Organization; 2023. Nakao T, Banba S, Broflanilide. A meta-diamide insecticide with a novel mode of action. Bioorg Med Chem. 2016;24:372–7. IRAC. IRAC MoA Group 30 IRM Guidelines. Hertford: Insecticide Resistance Action Committee; 2022. Lees RS, Ambrose P, Williams J, Morgan J, Praulins G, Ingham VA, et al. Tenebenal: a meta-diamide with potential for use as a novel mode of action insecticide for public health. Malar J. 2020;19:398. Ngufor C, Govoetchan R, Fongnikin A, Vigninou E, Syme T, Akogbeto M, et al. Efficacy of broflanilide (VECTRON T500), a new meta-diamide insecticide, for indoor residual spraying against pyrethroid-resistant malaria vectors. Sci Rep. 2021;11:8312. Dulacha D, Were V, Oyugi E, Etyang AO, Lako CA, Abong'o B, et al. Reduction in malaria burden following the introduction of indoor residual spraying in areas protected by long-lasting insecticidal nets in Western Kenya, 2016–2018. PLoS ONE. 2022;17:e0266736. KMIS. Kenya Malaria Indicator Survey 2020. Nairobi: Kenya National Bureau of Statistics; 2020. Okoyo C, Githinji E, Muia RW, Chesang K, Gachoya M, Ng'ang'a Z, et al. Assessment of malaria infection among pregnant women and children below five years of age attending rural health facilities of Kenya. PLoS ONE. 2021;16:e0257276. Li H, Wang L, Chen X, Sha J, Yin M, Gao B, et al. Adapting to the heat, fighting with the bite: A two-fold risk assessment coupling indoor heat stress and malaria disease in traditional African settlements. Build Environ. 2024;251:111194. WHO. Standard operating procedure for testing insecticide susceptibility of adult mosquitoes in WHO tube tests. Geneva: World Health Organization; 2022. Brogdon WG, McAllister JC. Insecticide resistance and vector control. Emerg Infect Dis. 1998;4:605–13. Wilkins EE, Howell PI, Benedict MQ. IMP PCR primers detect single nucleotide polymorphisms for Anopheles gambiae species identification, Mopti and Savanna rDNA types, and resistance to dieldrin in Anopheles arabiensis. Malar J. 2006;5:125. Koekemoer LL, Kamau L, Hunt RH, Coetzee M. A cocktail polymerase chain reaction assay to identify members of the Anopheles funestus (Diptera: Culicidae) group. Am J Trop Med Hyg. 2002;66:804–11. Sibanda MM, Focke WW, Labuschagne FJWJ, Moyo L, Nhlapo N, Mofokeng T, et al. Physical, chemical and insecticidal properties of handcrafted mud walls in rural areas of Africa. Mater Des. 2021;210:110057. Yewhalaw D, Getachew Y, Tushune K, Michael KW, Kassahun W, Duchateau L, et al. The effect of drying and aging of spray surfaces on bioefficacy of indoor residual spraying against wild populations of Anopheles arabiensis in Ethiopia. Parasit Vectors. 2022;15:86. Govoetchan R, Fongnikin A, Syme T, Small G, Gbegbo M, Todjinou D, et al. VECTRON™ T500, a new broflanilide insecticide for indoor residual spraying, provides prolonged control of pyrethroid-resistant malaria vectors. Malar J. 2022;21:324. Ngufor C, Govoetchan R, Fongnikin A, Vigninou E, Syme T, Akogbeto M, et al. Efficacy of broflanilide (VECTRON T500), a new meta-diamide insecticide, for indoor residual spraying against pyrethroid-resistant malaria vectors. Sci Rep. 2021;11:7976. Mbewe NJ, Kirby MJ, Snetselaar J, Kaaya RD, Small G, Azizi S, et al. A non-inferiority and GLP-compliant study of broflanilide IRS (VECTRON™ T500), a novel meta-diamide insecticide against Anopheles arabiensis. Front Trop Dis. 2023;4:1126869. Tungu PK, Rowland MW, Messenger LA, Small GJ, Bradley J, Snetselaar J, et al. Large-scale (Phase III) evaluation of broflanilide 50WP (VECTRON™ T500) for indoor residual spraying for malaria vector control in Northeast Tanzania: study protocol for a two-arm, non-inferiority, cluster-randomised community trial. BMC Infect Dis. 2022;22:171. Ngufor C, Govoetchan R, Fongnikin A, Hueha C, Ahoga J, Syme T, et al. Community evaluation of VECTRON™ T500, a broflanilide insecticide, for indoor residual spraying for malaria vector control in central Benin; a two arm non-inferiority cluster randomised trial. Sci Rep. 2023;13:17852. Portwood NM, Shayo MF, Tungu PK, Mbewe NJ, Mlay G, Small G, et al. Multi-centre discriminating concentration determination of broflanilide and potential for cross-resistance to other public health insecticides in Anopheles vector populations. Sci Rep. 2022;12:22359. Coetzee M, Hunt RH, Wilkerson R, Della Torre A, Coulibaly MB, Besansky NJ. Anopheles coluzzii and Anopheles amharicus, new members of the Anopheles gambiae complex. Zootaxa. 2013;3619:246–74. Matowo NS, Munhenga G, Tanner M, Coetzee M, Ferreira PE, Ngowi V, et al. Fine-scale spatial and temporal heterogeneities in insecticide resistance profiles of the malaria vector, Anopheles arabiensis in rural south-eastern Tanzania. Wellcome Open Res. 2017;2:96. WHO. Global report on insecticide resistance in malaria vectors: 2010–2019. Geneva: World Health Organization; 2022. Lees RS, Ambrose P, Williams J, Morgan J, Praulins G, Ingham VA, et al. Tenebenal: a meta-diamide with potential for use as a novel mode of action insecticide for public health. Malar J. 2020;19:398. Gleave K, Lissenden N, Chaplin M, Choi L, Ranson H. Piperonyl butoxide (PBO) combined with pyrethroids in insecticide-treated nets to prevent malaria in Africa. Cochrane Database Syst Rev. 2021;5:CD012776. Hien AS, Bayili K, Maiga S, Oumbouke W, Birba J, Soma DD, et al. Long-lasting residual efficacy of a new indoor residual spraying product, VECTRON™ T500 (broflanilide), against pyrethroid-resistant malaria vectors and its acceptance in a community trial in Burkina Faso. Parasit Vectors. 2024;17:484. Ingabire CM, Rulisa A, Van Kempen L, Muvunyi C, Koenraadt CJ, Van Vugt M, et al. Factors impeding the acceptability and use of malaria preventive measures: implications for malaria elimination in eastern Rwanda. Malar J. 2015;14:136. Makungu C, Stephen S, Kumburu S, Juma O, Kilama M, Kahesa C, et al. Informing new or improved vector control tools for reducing the malaria burden in Tanzania: a qualitative exploration of perceptions of mosquitoes and methods for their control among the residents of Dar es Salaam. Malar J. 2017;16:410. Mbewe NJ, Tungu PK, Messenger LA, Bradley J, Mangesho PE, Shirima B, et al. A noninferiority cluster randomised evaluation of a broflanilide indoor residual spraying insecticide, VECTRON T500, for malaria vector control in Tanzania. Sci Rep. 2025;15:15013. Nakao T, Banba S, Broflanilide. A meta-diamide insecticide with a novel mode of action. Bioorg Med Chem. 2016;24:372–7. Birget PLG, Koella JC. An epidemiological model of the effects of insecticide-treated bed nets on malaria transmission. PLoS ONE. 2015;10:e0144173. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 29 Nov, 2025 Read the published version in Malaria Journal → Version 1 posted Editorial decision: Revision requested 05 Oct, 2025 Reviews received at journal 06 Sep, 2025 Reviews received at journal 01 Sep, 2025 Reviewers agreed at journal 20 Aug, 2025 Reviewers agreed at journal 18 Aug, 2025 Reviewers agreed at journal 17 Aug, 2025 Reviewers invited by journal 17 Aug, 2025 Editor assigned by journal 02 Jul, 2025 Submission checks completed at journal 02 Jul, 2025 First submitted to journal 01 Jul, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7021640","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":503616055,"identity":"15554ebf-5ce5-463c-a21a-166db89e68e2","order_by":0,"name":"Celestine N. Wekesa","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAyElEQVRIiWNgGAWjYFAC5gYGhgMMciDmgQfEaWEEazEGa0kgRUtiA4hNlBb+9sY2iQ9n6tLnhx1+CLTFTk63gYAWiTMH2yRn3Dicu/F2mgFQS7Kx2QECWgwkEttu83w4kLtxdgJIy4HEbQS1yD9su/3nQ1264ez0D0RqkWBsu81wgzlBXjqHSFskziS2/+w5c9hwg3ROwYEEAyL8wt9++LDBj2N18vKz0zd/+FBhJ0dQC8KFYJUGxCoHAfkGUlSPglEwCkbBiAIAjJtMzuDeOSkAAAAASUVORK5CYII=","orcid":"","institution":"Maseno University","correspondingAuthor":true,"prefix":"","firstName":"Celestine","middleName":"N.","lastName":"Wekesa","suffix":""},{"id":503616057,"identity":"9007980f-6723-4480-8a4d-bc076f946b8c","order_by":1,"name":"Brian Polo","email":"","orcid":"","institution":"1.\tKenya Medical Research Institute, Centre for Global Health Research, Kisumu, Kenya.","correspondingAuthor":false,"prefix":"","firstName":"Brian","middleName":"","lastName":"Polo","suffix":""},{"id":503616059,"identity":"7ecf38da-e30b-41ea-b0b9-fedc351fc20f","order_by":2,"name":"Margaret Muchoki","email":"","orcid":"","institution":"1.\tKenya Medical Research Institute, Centre for Global Health Research, Kisumu, Kenya.","correspondingAuthor":false,"prefix":"","firstName":"Margaret","middleName":"","lastName":"Muchoki","suffix":""},{"id":503616060,"identity":"89c9456f-cc08-430b-af6e-1bd0b63d7fb9","order_by":3,"name":"Seline Omondi","email":"","orcid":"","institution":"1.\tKenya Medical Research Institute, Centre for Global Health Research, Kisumu, Kenya.","correspondingAuthor":false,"prefix":"","firstName":"Seline","middleName":"","lastName":"Omondi","suffix":""},{"id":503616062,"identity":"d40e5eae-9b77-4d17-97c7-fb86088bc924","order_by":4,"name":"David Sang","email":"","orcid":"","institution":"Maseno University","correspondingAuthor":false,"prefix":"","firstName":"David","middleName":"","lastName":"Sang","suffix":""},{"id":503616064,"identity":"8269598a-f8cb-4ffc-9c0a-e09dc7b615d0","order_by":5,"name":"Matthew Kipsum","email":"","orcid":"","institution":"1.\tKenya Medical Research Institute, Centre for Global Health Research, Kisumu, Kenya.","correspondingAuthor":false,"prefix":"","firstName":"Matthew","middleName":"","lastName":"Kipsum","suffix":""},{"id":503616066,"identity":"ec6ffdf4-dc83-4441-b510-e356c831410a","order_by":6,"name":"Bernard Abong’o","email":"","orcid":"","institution":"1.\tKenya Medical Research Institute, Centre for Global Health Research, Kisumu, Kenya.","correspondingAuthor":false,"prefix":"","firstName":"Bernard","middleName":"","lastName":"Abong’o","suffix":""},{"id":503616067,"identity":"939fdef0-ec62-4012-8fae-ea3d3f85d5fd","order_by":7,"name":"Maxwell G. Machani","email":"","orcid":"","institution":"1.\tKenya Medical Research Institute, Centre for Global Health Research, Kisumu, Kenya.","correspondingAuthor":false,"prefix":"","firstName":"Maxwell","middleName":"G.","lastName":"Machani","suffix":""},{"id":503616076,"identity":"ba76dddb-e716-4756-a506-46396cb2c037","order_by":8,"name":"Teresa Bange","email":"","orcid":"","institution":"1.\tKenya Medical Research Institute, Centre for Global Health Research, Kisumu, Kenya.","correspondingAuthor":false,"prefix":"","firstName":"Teresa","middleName":"","lastName":"Bange","suffix":""},{"id":503616079,"identity":"072b410f-52ea-43d6-81ee-6f8a440f5910","order_by":9,"name":"Ismael Abbey","email":"","orcid":"","institution":"3.\tNational Malaria Control Programme, Ministry of Health, Kenyatta National Hospital Kenya.","correspondingAuthor":false,"prefix":"","firstName":"Ismael","middleName":"","lastName":"Abbey","suffix":""},{"id":503616081,"identity":"97334920-386d-484b-80f4-75161bcde630","order_by":10,"name":"Paul Kiptoo","email":"","orcid":"","institution":"3.\tNational Malaria Control Programme, Ministry of Health, Kenyatta National Hospital Kenya.","correspondingAuthor":false,"prefix":"","firstName":"Paul","middleName":"","lastName":"Kiptoo","suffix":""},{"id":503616084,"identity":"b24c0081-fdcf-4a2a-a2f9-d65ab78084d6","order_by":11,"name":"Patrick Mburugu","email":"","orcid":"","institution":"3.\tNational Malaria Control Programme, Ministry of Health, Kenyatta National Hospital Kenya.","correspondingAuthor":false,"prefix":"","firstName":"Patrick","middleName":"","lastName":"Mburugu","suffix":""},{"id":503616088,"identity":"98b7024f-eb9f-44f4-8783-2d67b19ac618","order_by":12,"name":"Kibor Keitany","email":"","orcid":"","institution":"3.\tNational Malaria Control Programme, Ministry of Health, Kenyatta National Hospital Kenya.","correspondingAuthor":false,"prefix":"","firstName":"Kibor","middleName":"","lastName":"Keitany","suffix":""},{"id":503616089,"identity":"aa43d1f3-ae48-48ff-a927-89bb399d922c","order_by":13,"name":"Edith Ramaita","email":"","orcid":"","institution":"3.\tNational Malaria Control Programme, Ministry of Health, Kenyatta National Hospital Kenya.","correspondingAuthor":false,"prefix":"","firstName":"Edith","middleName":"","lastName":"Ramaita","suffix":""},{"id":503616090,"identity":"215d7072-3fc6-4486-91c5-f722a6599a17","order_by":14,"name":"Eric Ochomo","email":"","orcid":"","institution":"Kenya Medical Research Institute, Centre for Infectious and Parasitic Disease Control Research","correspondingAuthor":false,"prefix":"","firstName":"Eric","middleName":"","lastName":"Ochomo","suffix":""}],"badges":[],"createdAt":"2025-07-01 15:08:06","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7021640/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7021640/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12936-025-05688-w","type":"published","date":"2025-11-29T15:57:38+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":89857346,"identity":"bff61593-747d-409d-ac67-8e42fc1f2931","added_by":"auto","created_at":"2025-08-25 19:32:10","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":337901,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of 24-hour mortality rates (with 95% confidence intervals) following WHO cone bioassay exposure to VECTRON™ T500 and Actellic™ 300CS over six months. VECTRON™ T500 maintained \u0026gt;95% mortality while Actellic™ 300CS fell below the 80% WHO threshold after month 4. Abbott's formula was applied to correct for control mortality \u0026gt;5%.\u003c/p\u003e","description":"","filename":"Figure1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7021640/v1/0c0c2d0e9ca25d67c39a5e56.jpg"},{"id":89857350,"identity":"b9106281-0579-4eef-97c8-094abc7298fd","added_by":"auto","created_at":"2025-08-25 19:32:10","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":348743,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of 24-hour mortality rates (with 95% confidence intervals) following WHO cone bioassay exposure to VECTRON™ T500 and Actellic™ 300CS over six months. VECTRON™ T500 maintained 100% mortality throughout while Actellic™ 300CS showed declining efficacy. Abbott's formula was applied to correct for control mortality \u0026gt;5%.\u003c/p\u003e","description":"","filename":"Figure2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7021640/v1/5ffc593ad21f84486fd61b87.jpg"},{"id":89857349,"identity":"82cc9ffe-a761-4382-a9c5-808cca39e918","added_by":"auto","created_at":"2025-08-25 19:32:10","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":261849,"visible":true,"origin":"","legend":"\u003cp\u003eMean adjusted mortality rates comparing VECTRON™ T500 and Actellic™ 300CS performance on mud and cement wall surfaces for both resistant and susceptible mosquito strains. VECTRON™ T500 showed superior performance on both wall types with minimal variation between surfaces.\u003c/p\u003e","description":"","filename":"Figure3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7021640/v1/025bd3a1bb2caeeb32d3e935.jpg"},{"id":89857351,"identity":"f66556dd-0399-469f-ba05-61886ea6ae80","added_by":"auto","created_at":"2025-08-25 19:32:10","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":146441,"visible":true,"origin":"","legend":"\u003cp\u003eMean percentage mortality (with 95% confidence intervals) of field-collected \u003cem\u003eAn. gambiae\u003c/em\u003e s.l. and \u003cem\u003eAn. funestus\u003c/em\u003e s.l. after exposure to broflanilide and pirimiphos-methyl in CDC bottle bioassays. Both species showed 100% susceptibility with no evidence of cross-resistance.\u003c/p\u003e","description":"","filename":"Figure4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7021640/v1/e89fe97881d0b018db979602.jpg"},{"id":97179897,"identity":"4036c454-0786-4399-a8f3-31f7e9c40287","added_by":"auto","created_at":"2025-12-01 16:17:10","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1988749,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7021640/v1/0c2884a2-9308-4113-a577-1099b1c63970.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Community evaluation of VECTRON™ T500 (broflanilide) for indoor residual spraying for malaria vector control in Siaya county, Kenya","fulltext":[{"header":"Background","content":"\u003cp\u003eVector control has significantly reduced malaria transmission across endemic regions with varying epidemiological conditions [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Indoor residual spraying (IRS), involving treatment of interior house surfaces with residual insecticide formulations, remains a core intervention as demonstrated during the global malaria eradication program [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. According to WHO reports, IRS protected approximately 1.6% of at-risk populations globally in malaria endemic countries with 88.4% coverage of target structures [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eIRS targets adult mosquitoes feeding indoors (endophagic) and resting indoors (endophilic) through repellency effects or by killing them when they contact treated surfaces with lethal insecticide concentrations [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Massive vector population declines and reduced longevity from IRS effectively reduce malaria transmission through decreased vectorial capacity [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Sustainable IRS implementation has substantially impacted malaria prevalence globally, especially in high transmission areas [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eWHO-recommended insecticide classes for IRS include pyrethroids, organochlorines, carbamates, organophosphates, neonicotinoids, and pyrroles [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Prolonged reliance on single insecticide classes increases resistance, reducing IRS efficacy [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Resistance to organophosphates, pyrethroids, carbamates, and organochlorines has been reported globally with varying intensities across WHO regions [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. To mitigate resistance development, WHO recommends four strategies (mixtures, rotations, mosaics, and combinations) to preserve vector susceptibility [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eAvailable insecticidal products are insufficient to meet growing malaria vector control challenges due to limited alternative insecticides [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Consistent innovation of new products that overcome resistance, have longer residual effects, and maintain efficacy in high transmission areas continues [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Conventional IRS insecticides display two major biochemical modes of action: sodium channel disruption (pyrethroids and organochlorines) and acetylcholinesterase inhibition (organophosphates and carbamates) [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eNext-generation insecticides include chlorfenapyr (pyrrole class) with distinctive oxidative phosphorylation uncoupling in insect mitochondria [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e], neonicotinoids like clothianidin acting through nicotinic acetylcholine receptor overstimulation [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e], indoxacarb blocking sodium ion channels, and insect growth regulators disrupting development through juvenile hormone mimicking or inhibition [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eVECTRON™ T500, a wettable powder formulation containing broflanilide produced by Mitsui Chemicals Crop \u0026amp; Life Solutions, Inc. (MCCLS), is among the most recently WHO-prequalified IRS insecticides [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Broflanilide contains a meta-diamide chemical structure offering a novel mode of action against malaria vectors compared to existing IRS insecticide classes [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. It functions by inhibiting neurotransmission through non-competitive antagonism of γ-aminobutyric acid (GABA) receptors on chloride-gated channels, causing hyperexcitation, convulsion, and death [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eMeta-diamides and isoxazolines (Group 30 insecticides - GABA-gated chloride channel allosteric modulators) are characterized by long residual activity and effectiveness against pyrethroid-resistant insects on different substrates [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Broflanilide's novel GABA receptor targeting provides significant resistance management advantages, representing a distinctive class creating opportunities for effective rotation strategies [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. This unique mechanism may explain the absence of cross-resistance with existing resistance mechanisms in African malaria vectors [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eComparing VECTRON™ T500 with Actellic™ 300CS (pirimiphos-methyl) is particularly relevant as the latter represents the first-in-class organophosphate widely deployed for IRS in Kenya since 2017 following widespread pyrethroid resistance development [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. This study, required by Kenya's Pest Control Products Board (PCPB) for VECTRON™ T500 registration, evaluated residual efficacy compared to Actellic™ 300CS on pyrethroid-resistant and susceptible \u003cem\u003eAn. gambiae\u003c/em\u003e s.s. strains, with secondary endpoints including community acceptability and safety.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e\u003cb\u003eStudy Area\u003c/b\u003e\u003c/p\u003e\u003cp\u003eThis study was conducted in Bar Olengo location (-0.0728262°N, 34.6699246°E), Bondo sub-county, Siaya County, Kenya. Siaya County, located in western Kenya and bordered by Lake Victoria, provides favorable mosquito breeding environments. The county has high malaria prevalence, ranking second nationally [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. Current vector control relies solely on pyrethroid-only insecticide-treated nets (ITNs).\u003c/p\u003e\u003cp\u003eThe area receives 800-2000mm annual bimodal rainfall with 60–80% humidity. Annual mean temperatures range 30–35°C, favoring malaria vector survival and breeding [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. Principal vectors are \u003cem\u003eAn. funestus\u003c/em\u003e s.s., \u003cem\u003eAn. gambiae\u003c/em\u003e s.s., and \u003cem\u003eAn. arabiensis\u003c/em\u003e, all exhibiting high-intensity pyrethroid resistance. Main economic activities include fishing, rice farming, livestock raising, small-scale trading, and gold mining.\u003c/p\u003e\u003cp\u003e\u003cb\u003eStudy Design and Randomization\u003c/b\u003e\u003c/p\u003e\u003cp\u003eA longitudinal two-arm evaluation study was conducted between June and November 2024. The study area was stratified by village (Waga and Bungu), then by wall type (mud and cement) to ensure balanced representation. Using computer-generated random numbers, 25 eligible structures from each village were selected with equal wall type allocation. VECTRON™ T500 was applied in Waga village while Actellic™ 300CS was applied in Bungu village, with 5 randomly selected structures per village serving as negative controls (water-sprayed).\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eSample Size Calculation\u003c/strong\u003e\u003c/p\u003e\u003cp\u003eBased on previous IRS efficacy studies and assuming 90% mortality for the control product with 80% power to detect a 10% difference at 5% significance level, 25 structures per arm provided adequate power for non-inferiority testing.\u003c/p\u003e\u003cp\u003e\u003cb\u003eTest Products and Application\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eVECTRON™ T500\u003c/strong\u003e\u003c/p\u003e\u003cp\u003eWettable powder containing 50% broflanilide active ingredient, supplied in 50g sachets and applied at 100mg a.i/m². Full safety information, toxicological reports, and certificates of analysis were provided by MCCLS.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eActellic™ 300CS\u003c/strong\u003e\u003c/p\u003e\u003cp\u003ePirimiphos-methyl applied at 1g a.i/m² as positive control.\u003c/p\u003e\u003cp\u003e\u003cb\u003eResidual Efficacy Assessment\u003c/b\u003e\u003c/p\u003e\u003cp\u003eWHO cone bioassays followed standard guidelines [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e] at 7 days post-spraying for quality assessment, then monthly for six months evaluating residual efficacy. Ten households per village were randomly selected, stratified by wall type (5 mud, 5 cement). Cone bioassays used 2-5-day-old non-blood-fed females from two laboratory colonies:\u003c/p\u003e\u003cul\u003e\u003cli\u003e\u003cp\u003ePyrethroid-resistant \u003cem\u003eAn. gambiae\u003c/em\u003e s.s. Bungoma strain (elevated P450 enzymes, Ace-1 mutations, kdr polymorphisms)\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eSusceptible \u003cem\u003eAn. gambiae\u003c/em\u003e s.s. Kisumu strain\u003c/p\u003e\u003c/li\u003e\u003c/ul\u003e\u003cp\u003eBioassays were conducted at three heights (0.5, 1.0, 1.5 meters) on different walls per room. Two cones per test point exposed 10 mosquitoes each for 30 minutes. Mosquitoes were aspirated into labeled cups; knockdown was recorded at 60 minutes, mortality monitored at 24, 48, and 72 hours under controlled conditions (27 ± 2°C, 80 ± 10% relative humidity). Control assays on unsprayed surfaces applied Abbott's formula when control mortality exceeded 5% but remained below 20%. Assays with \u0026gt; 20% control mortality were repeated.\u003c/p\u003e\u003cp\u003e\u003cb\u003eWild Vector Susceptibility Testing\u003c/b\u003e\u003c/p\u003e\u003cp\u003eComprehensive bioassays established insecticide resistance status. \u003cem\u003eAn. gambiae\u003c/em\u003e s.l. larvae were collected from multiple breeding sites before spraying and reared to adulthood. Blood-fed adult \u003cem\u003eAn. funestus\u003c/em\u003e were collected using mouth aspirators for F₀ generation testing.\u003c/p\u003e\u003cp\u003eStandard WHO tube bioassays used diagnostic concentrations: deltamethrin (0.05%), permethrin (0.75%), alpha-cypermethrin (0.05%), and pirimiphos-methyl (0.25%). Resistance intensity bioassays used 5× and 10× diagnostic concentrations. Synergist assays exposed mosquitoes to 4% piperonyl butoxide (PBO) for 1 hour before pyrethroid exposure.\u003c/p\u003e\u003cp\u003eCDC bottle bioassays for broflanilide and pirimiphos-methyl followed established methods [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e] with discriminating concentrations: 6 µg/bottle with 800 ppm Mero adjuvant for broflanilide and 20 µg/bottle for pirimiphos-methyl. Knockdown was recorded at 60 minutes, mortality at 24 hours for pyrethroids and pirimiphos-methyl, 48 hours for broflanilide. Four replicates with 20–25 unfed mosquitoes per replicate were used per insecticide.\u003c/p\u003e\u003cp\u003eMolecular assays identified \u003cem\u003eAn. gambiae\u003c/em\u003e complex [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e] and \u003cem\u003eAn. funestus\u003c/em\u003e complex [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e] species. Resistance status classification followed WHO criteria: ≥98% mortality (susceptible), 90–97% (possible resistance), \u0026lt; 90% (confirmed resistance).\u003c/p\u003e\u003cp\u003e\u003cb\u003eCommunity Acceptability and Adverse Events\u003c/b\u003e\u003c/p\u003e\u003cp\u003eBaseline questionnaires captured pre-intervention health status. Questionnaires were administered to household heads on spraying day, one week post-spraying, and monthly for six months, determining factors influencing VECTRON™ T500 acceptability compared to Actellic™ 300CS. User acceptability was calculated as the ratio of household refusals to total structures sprayed, recording refusal reasons.\u003c/p\u003e\u003cp\u003eThree months post-intervention, 20 audio-recorded in-depth interviews assessed product acceptability among end-users and spray operators. Eight households per arm were randomly interviewed, evenly split between wall types. Four spray operators familiar with both products explored knowledge, perceptions, and experiences.\u003c/p\u003e\u003cp\u003eApparently healthy sprayers were enrolled after pre-spray questionnaire screening. Daily post-spray questionnaires captured adverse events experienced during and after spraying. Household heads received adverse events questionnaires for six months in both intervention areas and controls. Both sprayers and householders were encouraged to report suspected insecticide-related symptoms immediately.\u003c/p\u003e\u003ch2\u003eStatistical Analysis\u003c/h2\u003e\u003cp\u003eData collection used CommCare™ application with structured questionnaires. Residual efficacy analysis calculated mortality means from both arms and negative controls. Independent t-tests determined mortality differences with effect sizes calculated using Cohen's d. Control mortality \u0026gt; 5% was adjusted using Abbott's formula.\u003c/p\u003e\u003cp\u003eSusceptibility test data analyzed mortality means from each insecticide tested. Community acceptability was calculated as mean household refusals to total sprayed structures, analyzed using independent t-tests. In-depth interview audio records were transcribed and coded using NVivo version 14. Codebook-guided initial deductive coding while inductive coding captured emerging themes. Thematic synthesis identified patterns across codes and respondent categories.\u003c/p\u003e\u003cp\u003eAdverse events were calculated by finding means of reported symptoms and analyzed using independent t-tests. Statistical analysis and visualization used R version 4.4.0.\u003c/p\u003e\u003cp\u003e\u003cb\u003eEthical and Regulatory Considerations\u003c/b\u003e\u003c/p\u003e\u003cp\u003eThis study was conducted under PCPB trial permit PCPB/Eval/Vol.I/24/44. The protocol was approved by Kenya Medical Research Institute's Scientific and Ethics Review Unit (SERU 4536). Community consent was obtained from Siaya County health department, local chiefs, village leaders, and community health promoters. Written informed consent was obtained from household heads and sprayers.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003eResidual Efficacy\u003c/strong\u003e\u003cp\u003eVECTRON\u0026trade; T500 consistently maintained higher mortality than Actellic\u0026trade; 300CS throughout the six-month period on both wall surfaces. For resistant \u003cem\u003eAn. gambiae\u003c/em\u003e s.s. Bungoma strain, VECTRON\u0026trade; T500 induced 98.73\u0026thinsp;\u0026plusmn;\u0026thinsp;3.51% mortality compared to 80.22\u0026thinsp;\u0026plusmn;\u0026thinsp;11.23% for Actellic\u0026trade; 300CS (t₇₈=-10.15, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001, Cohen's d\u0026thinsp;=\u0026thinsp;2.27) (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). For susceptible \u003cem\u003eAn. gambiae\u003c/em\u003e s.s. Kisumu strain, VECTRON\u0026trade; T500 maintained 100% mortality versus 89.60\u0026thinsp;\u0026plusmn;\u0026thinsp;6.34% for Actellic\u0026trade; 300CS (t₇₈=10.53, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001, Cohen's d\u0026thinsp;=\u0026thinsp;2.38) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/p\u003e\u003cp\u003eCritically, Actellic\u0026trade; 300CS efficacy declined below the WHO-recommended 80% threshold after month 4 for resistant mosquitoes, dropping to 76.2% in month 5 and 71.8% in month 6. VECTRON\u0026trade; T500 maintained\u0026thinsp;\u0026gt;\u0026thinsp;95% mortality throughout the entire evaluation period, never falling below 96.5% for any strain or time point (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eMonthly mortality rates (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation) of pyrethroid-resistant An. gambiae s.s. Bungoma strain and susceptible An. gambiae s.s. Kisumu strain following exposure to VECTRON\u0026trade; T500 (100 mg a.i./m\u0026sup2;) and Actellic\u0026trade; 300CS (1000 mg a.i./m\u0026sup2;) treated surfaces in WHO cone bioassays over six months post-application. Mortality was assessed at 72 hours post-exposure. Control mortality\u0026thinsp;\u0026gt;\u0026thinsp;5% was corrected using Abbott's formula. WHO efficacy threshold for IRS products is \u0026ge;\u0026thinsp;80% mortality.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMonth\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eVECTRON\u0026trade; T500\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eActellic\u0026trade; 300CS\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eResistant (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eSusceptible (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eResistant (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eSusceptible (%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e100.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e100.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e92.3\u0026thinsp;\u0026plusmn;\u0026thinsp;4.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e96.8\u0026thinsp;\u0026plusmn;\u0026thinsp;2.1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e99.2\u0026thinsp;\u0026plusmn;\u0026thinsp;1.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e100.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e88.7\u0026thinsp;\u0026plusmn;\u0026thinsp;6.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e94.2\u0026thinsp;\u0026plusmn;\u0026thinsp;3.6\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e98.9\u0026thinsp;\u0026plusmn;\u0026thinsp;2.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e100.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e85.4\u0026thinsp;\u0026plusmn;\u0026thinsp;8.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e91.5\u0026thinsp;\u0026plusmn;\u0026thinsp;4.8\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e98.1\u0026thinsp;\u0026plusmn;\u0026thinsp;2.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e100.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e79.8\u0026thinsp;\u0026plusmn;\u0026thinsp;9.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e88.7\u0026thinsp;\u0026plusmn;\u0026thinsp;5.2\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e97.8\u0026thinsp;\u0026plusmn;\u0026thinsp;3.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e100.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e76.2\u0026thinsp;\u0026plusmn;\u0026thinsp;11.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e85.3\u0026thinsp;\u0026plusmn;\u0026thinsp;6.8\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e96.5\u0026thinsp;\u0026plusmn;\u0026thinsp;3.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e100.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e71.8\u0026thinsp;\u0026plusmn;\u0026thinsp;12.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e82.1\u0026thinsp;\u0026plusmn;\u0026thinsp;7.4\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eResidual efficacy of the IRS products on different wall types\u003c/strong\u003e\u003cp\u003eMortality means for resistant \u003cem\u003eAn. gambiae\u003c/em\u003e s.s. Bungoma strain were higher with VECTRON\u0026trade; T500 on both cement (98.66\u0026thinsp;\u0026plusmn;\u0026thinsp;3.56%) and mud (100%) walls compared to Actellic\u0026trade; 300CS on cement (78.82\u0026thinsp;\u0026plusmn;\u0026thinsp;15.57%) and mud (77.75\u0026thinsp;\u0026plusmn;\u0026thinsp;11.69%) walls. Statistically significant differences existed for cement walls (t₁₂=3.286, p\u0026thinsp;=\u0026thinsp;0.007) and mud walls (t₁₂=5.037, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Mortality was observed to fall below 80% at month 4 in the Actellic\u0026trade; 300CS arm (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/p\u003e\u003cp\u003eFor susceptible \u003cem\u003eAn. gambiae\u003c/em\u003e s.s. Kisumu strain, VECTRON\u0026trade; T500 maintained 100% mortality on both wall types compared to Actellic\u0026trade; 300CS cement (88.01\u0026thinsp;\u0026plusmn;\u0026thinsp;8.5%) and mud (86.65\u0026thinsp;\u0026plusmn;\u0026thinsp;6.64%) performance. Significant differences were observed for cement (t₁₂=3.700, p\u0026thinsp;=\u0026thinsp;0.003) and mud (t₁₂=5.318, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) walls (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cb\u003eSusceptibility of wild\u003c/b\u003e \u003cb\u003eAnopheles\u003c/b\u003e \u003cb\u003emosquitoes to Broflanilide and pirimiphos methyl\u003c/b\u003e\u003c/p\u003e\u003cp\u003eAmong 2,400 wild vectors tested, molecular identification of 400 specimens revealed: 200 \u003cem\u003eAn. funestus\u003c/em\u003e s.l. (98% \u003cem\u003eAn. funestus\u003c/em\u003e s.s., 2% \u003cem\u003eAn. leesoni\u003c/em\u003e), 200 \u003cem\u003eAn. gambiae\u003c/em\u003e s.l. consisting 92% \u003cem\u003eAn. arabiensis\u003c/em\u003e, and 2% \u003cem\u003eAn. gambiae\u003c/em\u003e s.s, the rest were unamplified. CDC bottle bioassays showed Broflanilide induced 100% mortality in both \u003cem\u003eAn. gambiae\u003c/em\u003e s.l. and \u003cem\u003eAn. funestus\u003c/em\u003e s.l. with delayed mortality at 48 hours, indicating no cross-resistance detection. Pirimiphos-methyl similarly induced 100% mortality at 24 hours post-exposure (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e, Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eSusceptibility of field-collected An. gambiae s.l. and An. funestus s.l. to broflanilide, pirimiphos-methyl, and deltamethrin determined using WHO bottle bioassays and CDC bottle bioassays. Mosquitoes were exposed to diagnostic concentrations: broflanilide (6 \u0026micro;g/bottle with 800 ppm Mero adjuvant), pirimiphos-methyl (20 \u0026micro;g/bottle), and deltamethrin (12.5 \u0026micro;g/bottle). Piperonyl butoxide (PBO) synergist assays used 4% PBO pre-exposure for 1 hour before deltamethrin exposure. Mortality was recorded at 24 hours for deltamethrin and pirimiphos-methyl, and 48 hours for broflanilide. Resistance status classification follows WHO criteria: \u0026ge;98% mortality (susceptible), 90\u0026ndash;97% (possible resistance), \u0026lt;\u0026thinsp;90% (confirmed resistance). Data represent mean percentage mortality\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation with 95% confidence intervals.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSpecies\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eInsecticide\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eMortality (%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003e95% CI\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eStatus\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003eAn. gambiae\u003c/em\u003e s.l.\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eBroflanilide\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e100\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e100.0-100.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eSusceptible\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003eAn. funestus\u003c/em\u003e s.l.\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eBroflanilide\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e100\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e100.0-100.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eSusceptible\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003eAn. gambiae\u003c/em\u003e s.l.\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ePirimiphos-methyl\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e100\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e100.0-100.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eSusceptible\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003eAn. funestus\u003c/em\u003e s.l.\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ePirimiphos-methyl\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e100\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e100.0-100.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eSusceptible\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003eAn. gambiae\u003c/em\u003e s.l.\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eDeltamethrin\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e23.4\u0026thinsp;\u0026plusmn;\u0026thinsp;8.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e19.8\u0026ndash;27.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eResistant\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003eAn. funestus\u003c/em\u003e s.l.\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eDeltamethrin\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e31.2\u0026thinsp;\u0026plusmn;\u0026thinsp;9.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e26.4\u0026ndash;36.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eResistant\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003eAn. gambiae\u003c/em\u003e s.l.\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eDeltamethrin\u0026thinsp;+\u0026thinsp;PBO\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e100.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e100.0-100.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eSusceptible\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003eAn. funestus\u003c/em\u003e s.l.\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eDeltamethrin\u0026thinsp;+\u0026thinsp;PBO\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e89.3\u0026thinsp;\u0026plusmn;\u0026thinsp;6.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e85.1\u0026ndash;93.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eResistant\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eWild vector pyrethroid mortality fell below WHO resistance thresholds. PBO pre-exposure restored susceptibility to some pyrethroids, with full susceptibility only to deltamethrin (100\u0026thinsp;\u0026plusmn;\u0026thinsp;0%) and possible resistance to alpha-cypermethrin (97\u0026thinsp;\u0026plusmn;\u0026thinsp;3.83%) in \u003cem\u003eAn. gambiae\u003c/em\u003e s.l. Significant mortality differences existed between \u003cem\u003eAn. gambiae\u003c/em\u003e s.l. and \u003cem\u003eAn. funestus\u003c/em\u003e (t₂=-5.52, p\u0026thinsp;=\u0026thinsp;0.03) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cb\u003eAdverse Events and Safety\u003c/b\u003e\u003c/p\u003e\u003cp\u003eThroughout six months, 150 responses per intervention arm and five from negative controls were recorded. No adverse events were reported from VECTRON\u0026trade; T500 households (0/150), while Actellic\u0026trade; 300CS households reported adverse events in 8% of cases (12/150). Reported events included skin itchiness, facial burning, sneezing, eye irritation, and bad smell. Skin and facial burning was most frequent (2.7%, 4/150). Most adverse events occurred from spraying day to one-month post-spraying; none were reported after month 2.\u003c/p\u003e\u003cp\u003e\u003cb\u003eCommunity Acceptability\u003c/b\u003e\u003c/p\u003e\u003cp\u003eNo statistically significant difference existed in future acceptability between VECTRON\u0026trade; T500 (10.24%\u0026plusmn;12.25) and Actellic\u0026trade; 300CS (9.16%\u0026plusmn;12.44) (t₃₄=0.188, p\u0026thinsp;=\u0026thinsp;0.852). Main VECTRON\u0026trade; T500 acceptance factors were malaria reduction ability (48%, 72/150) and mosquito killing (31%, 47/150). For Actellic\u0026trade; 300CS, malaria reduction was the primary reason (37%, 56/150).\u003c/p\u003e\u003cp\u003eNo refusals occurred in VECTRON\u0026trade; T500 households throughout evaluation. Actellic\u0026trade; 300CS had 4% refusal (1/25), attributed to insecticide odor. Most participants from both wall types expressed willingness for future VECTRON\u0026trade; T500 spraying due to mosquito reduction.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe high residual efficacy of VECTRON\u0026trade; T500, maintaining\u0026thinsp;\u0026gt;\u0026thinsp;95% mortality throughout six months against both susceptible and resistant \u003cem\u003eAn. gambiae\u003c/em\u003e s.s. mosquitoes, represents compelling evidence for its potential in western Kenya's high-resistance contexts. The consistent performance across wall types addresses a critical operational challenge, as mud surfaces often present alkaline pH and porosity that can degrade or sequester active ingredients [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. The findings are consistent with recent experimental hut studies conducted in Benin [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e] and Tanzania [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e], which demonstrated prolonged efficacy of VECTRON\u0026trade; T500 against pyrethroid-resistant \u003cem\u003eAn. gambiae\u003c/em\u003e s.l. populations.\u003c/p\u003e\u003cp\u003eThe extended efficacy duration has significant programmatic implications. While Actellic\u0026trade; 300CS would require reapplication after 4 months to maintain WHO-recommended efficacy thresholds in this context, VECTRON\u0026trade; T500's sustained performance suggests potential for extended spray cycles. This could reduce operational costs, logistical demands, and household disruption while maintaining protection levels. Similar extended residual activity has been reported in experimental hut studies in Benin, where cone bioassay mortality remained\u0026thinsp;\u0026gt;\u0026thinsp;80% for 18 months [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e], and in Tanzania where efficacy persisted for 12 months [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. Community trials in Benin demonstrated that VECTRON\u0026trade; T500 maintained 100% mortality in wall cone bioassays for 24 months on both cement and mud walls [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eCost-effectiveness modelling based on these efficacy data would be valuable for program planning. Assuming similar application costs, the extended efficacy could translate to substantial savings through reduced spray frequencies. However, formal economic evaluation incorporating product costs, application expenses, and health outcomes is needed to quantify potential savings.\u003c/p\u003e\u003cp\u003eThis study represents the first comprehensive field evaluation of VECTRON\u0026trade; T500 against \u003cem\u003eAn. funestus\u003c/em\u003e s.l. populations. Previous evaluations have primarily focused on \u003cem\u003eAn. gambiae\u003c/em\u003e s.l. and \u003cem\u003eAn. arabiensis\u003c/em\u003e populations [\u003cspan additionalcitationids=\"CR31 CR32\" citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e], with \u003cem\u003eAn. funestus\u003c/em\u003e either absent from study sites or present in insufficient numbers for meaningful analysis. A recent multi-centre discriminating concentration study specifically noted that \"unfortunately, this was not feasible for inclusion... due to notorious difficulties rearing this particular species under controlled insectary conditions\" [\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe complete susceptibility of wild \u003cem\u003eAn. funestus\u003c/em\u003e s.l. to broflanilide (100% mortality at 6 \u0026micro;g/bottle) documented in this study is particularly significant given the critical role this species plays in malaria transmission across eastern and southern Africa [\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e, \u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e], making the efficacy of VECTRON\u0026trade; T500 against this species particularly valuable for elimination efforts. The GABA receptor targeting mechanism differs fundamentally from existing insecticide classes, providing genuine rotation options for sustainable resistance management [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e]. This finding aligns with previous laboratory and field studies that demonstrated no cross-resistance between broflanilide and pyrethroid resistance mechanisms in Burkina Faso, Benin, Tanzania[\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e, \u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e, \u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e], and now Kenya, suggesting broad applicability for resistance management across diverse vector populations.\u003c/p\u003e\u003cp\u003eThe absence of adverse events in VECTRON\u0026trade; T500 households versus 8% in Actellic\u0026trade; 300CS households, combined with 100% community acceptance, addresses critical implementation barriers. High refusal rates can compromise IRS coverage and effectiveness [\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e, \u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e]. The superior acceptability profile suggests VECTRON\u0026trade; T500 could achieve better coverage in operational settings. This safety profile is consistent with findings from community trials in Benin [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e] and Burkina Faso [\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e], where minimal to no adverse events were reported with VECTRON\u0026trade; T500. The primary acceptance drivers (malaria reduction and mosquito killing effectiveness) align with actual product performance, indicating realistic community perceptions. This concordance between expectations and performance suggests sustainable acceptance in repeated spray cycles, as demonstrated in the Burkina Faso study where acceptance remained high throughout a 12-month evaluation period [\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe performance of VECTRON\u0026trade; T500 compares favorably with other recently developed IRS formulations. Experimental hut studies comparing VECTRON\u0026trade; T500 with Actellic\u0026trade; 300CS in Benin showed non-inferiority in terms of mosquito mortality, with VECTRON\u0026trade; T500 demonstrating superior residual activity [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. Similarly, community trials comparing VECTRON\u0026trade; T500 with Fludora\u0026reg; Fusion in both Benin [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e] and Tanzania [\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e] demonstrated non-inferiority in reducing vector densities while showing extended residual efficacy. The delayed mortality characteristic of VECTRON\u0026trade; T500, attributed to its requirement for metabolic activation to desmethyl-broflanilide [\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e], has been observed consistently across studies. While this differs from the rapid knockdown effects of pyrethroids, modelling studies suggest that such slower-acting insecticides may be less likely to select for resistance [\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e], potentially extending their operational lifespan.\u003c/p\u003e\u003cp\u003eSeveral limitations warrant consideration. The six-month evaluation period, while comprehensive for regulatory purposes, may not capture long-term resistance development or efficacy decline. Extended monitoring would strengthen evidence for operational decision-making. Recent studies in Benin and Tanzania with longer follow-up periods (18\u0026ndash;24 months) have shown sustained efficacy [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e], suggesting that the performance observed in this study would likely continue beyond six months. The study design used village-level allocation rather than household randomization, potentially introducing geographical confounding. However, the stratification by wall type and similar baseline characteristics minimize this risk. Cost-effectiveness analysis was beyond this study's scope but represents a critical knowledge gap for program planning. The superior efficacy must be balanced against potential cost differences for informed product selection. Seasonal variations in efficacy were not fully captured given the June-November study period. Year-round evaluation would provide more comprehensive efficacy profiles under varying environmental conditions, as demonstrated in the Burkina Faso study which showed consistent performance across both dry and wet seasons [\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e].\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eVECTRON\u0026trade; T500 demonstrated superior residual efficacy compared to Actellic\u0026trade; 300CS, maintaining\u0026thinsp;\u0026gt;\u0026thinsp;95% mortality throughout six months against both susceptible and pyrethroid-resistant \u003cem\u003eAn. gambiae\u003c/em\u003e s.s. strains. Importantly, this study provides the first comprehensive field evidence of VECTRON\u0026trade; T500's efficacy against \u003cem\u003eAn. funestus\u003c/em\u003e s.l., showing complete susceptibility with no cross-resistance. The excellent safety profile with zero adverse events and 100% community acceptance collectively position VECTRON\u0026trade; T500 as a valuable tool for malaria vector control programs.\u003c/p\u003e\u003cp\u003eThe novel GABA receptor targeting mode of action provides genuine resistance management options, while extended residual activity offers potential operational advantages through reduced application frequency. These characteristics align with WHO Global Plan for Insecticide Resistance Management recommendations emphasizing rotation between insecticides with different modes of action [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe findings support incorporating VECTRON\u0026trade; T500 into resistance management strategies for sustainable malaria vector control, particularly in areas with high pyrethroid resistance or where \u003cem\u003eAn. funestus\u003c/em\u003e s.l. contributes significantly to transmission. The superior performance profile, combined with evidence from other African settings, warrants consideration for national malaria control program adoption, pending cost-effectiveness evaluation and regulatory approval.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003e\u0026deg;C\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eDegree Celsius\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003e\u0026micro;g\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eMicrogram\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eAce\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003e1-Acetylcholinesterase 1\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eAI\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eActive Ingredient; a.i/m\u0026sup2;-Active ingredient per square meter\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003e\u003cem\u003eAn.\u003c/em\u003e\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003e\u003cem\u003eAnopheles\u003c/em\u003e\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eCDC\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eCenters for Disease Control\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eCFV\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eControl Flow Valve\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eCGHR\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eCentre for Global Health Research\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eCHPs\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eCommunity Health Promoters\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eCI\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eConfidence Interval\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eF₀\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eParent generation\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eGABA\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eGamma-aminobutyric acid\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eIDI\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eIn-depth interview\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eIGRs\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eInsect Growth Regulators\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eIRAC\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eInsecticide Resistance Action Committee\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eIRS\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eIndoor Residual Spraying\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eIVCC\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eInnovative Vector Control Consortium\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003ekdr\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eKnockdown resistance\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eKEMRI\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eKenya Medical Research Institute\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eMCCLS\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eMitsui Chemicals Crop \u0026amp; Life Solutions Inc\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003enAChR\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eNicotinic acetylcholine receptors\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003ePBO\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003ePiperonyl butoxide; PCPB-Pest Control Products Board\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003ePPE\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003ePersonal Protective Equipment\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003es.l.\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003esensu lato; s.s.-sensu stricto\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eWHO\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eWorld Health Organization\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics Approval and Consent to Participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study protocol was approved by Kenya Medical Research Institute\u0026apos;s Scientific and Ethics Review Unit (SERU 4536). Written informed consent was obtained from all participants.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for Publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003ch2\u003eCompeting Interests\u003c/h2\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e\n\u003ch2\u003eFunding\u003c/h2\u003e\n\u003cp\u003eThis study was funded by Mitsui Chemicals Crop \u0026amp; Life Solutions, Inc. (MCCLS: Tokyo, Japan). The funder provided test materials and funding but was not involved in study design, data collection, analysis, or manuscript preparation.\u003c/p\u003e\n\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\n\u003cp\u003eEO, ER, BA, IA, PK, PM, KK, CW, MM, BP designed and implemented the study. MM, BP, EO mapped the study area and provided data collection tools. EO, ER, BA, IA, PK, PM, KK, CW, MM, BP supervised spray operations and ensured environmental compliance. BP and CW coordinated study activities including entomological surveys, bioassays, resistance monitoring, data analysis, and visualization. MK performed susceptibility assays. CW performed molecular assays for mosquito speciation. CW wrote the manuscript with assistance from EO and BP. TB and CW conducted adverse events and acceptability surveys. EO, BP, DS, SO, TB, and MGM reviewed the manuscript. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003ch2\u003eAcknowledgement\u003c/h2\u003e\n\u003cp\u003eThe authors thank Mitsui Chemicals Crop \u0026amp; Life Solutions, Inc. for providing test materials with full safety information, toxicological reports, and certificates of analysis. We acknowledge MCCLS and IVCC teams for manuscript review support. We thank Siaya County malaria control coordination team and Bar Olengo local administration for their support. We appreciate household owners for allowing structure enrollment and KEMRI/CGHR Entomology department technical staff for mosquito provision, bioassay testing, and molecular assays. We acknowledge the Pest Control Products Board, Ministry of Agriculture, for evaluation oversight.\u003c/p\u003e\n\u003ch2\u003eAvailability of Data and Materials\u003c/h2\u003e\n\u003cp\u003eThe data sets supporting the conclusion of this study is available within the article. Raw datasets are available from the corresponding authors on reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eBhatt S, Weiss DJ, Cameron E, Bisanzio D, Mappin B, Dalrymple U, et al. The effect of malaria control on Plasmodium falciparum in Africa between 2000 and 2015. Nature. 2015;526:207\u0026ndash;11.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWHO. Malaria eradication: Benefits, future scenarios and feasibility. 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Piperonyl butoxide (PBO) combined with pyrethroids in insecticide-treated nets to prevent malaria in Africa. Cochrane Database Syst Rev. 2021;5:CD012776.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHien AS, Bayili K, Maiga S, Oumbouke W, Birba J, Soma DD, et al. Long-lasting residual efficacy of a new indoor residual spraying product, VECTRON\u0026trade; T500 (broflanilide), against pyrethroid-resistant malaria vectors and its acceptance in a community trial in Burkina Faso. Parasit Vectors. 2024;17:484.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eIngabire CM, Rulisa A, Van Kempen L, Muvunyi C, Koenraadt CJ, Van Vugt M, et al. Factors impeding the acceptability and use of malaria preventive measures: implications for malaria elimination in eastern Rwanda. Malar J. 2015;14:136.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMakungu C, Stephen S, Kumburu S, Juma O, Kilama M, Kahesa C, et al. Informing new or improved vector control tools for reducing the malaria burden in Tanzania: a qualitative exploration of perceptions of mosquitoes and methods for their control among the residents of Dar es Salaam. Malar J. 2017;16:410.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMbewe NJ, Tungu PK, Messenger LA, Bradley J, Mangesho PE, Shirima B, et al. A noninferiority cluster randomised evaluation of a broflanilide indoor residual spraying insecticide, VECTRON T500, for malaria vector control in Tanzania. Sci Rep. 2025;15:15013.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eNakao T, Banba S, Broflanilide. A meta-diamide insecticide with a novel mode of action. Bioorg Med Chem. 2016;24:372\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBirget PLG, Koella JC. An epidemiological model of the effects of insecticide-treated bed nets on malaria transmission. PLoS ONE. 2015;10:e0144173.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"malaria-journal","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"malj","sideBox":"Learn more about [Malaria Journal](http://malariajournal.biomedcentral.com/)","snPcode":"12936","submissionUrl":"https://submission.nature.com/new-submission/12936/3","title":"Malaria Journal","twitterHandle":"@malariajournal","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Indoor residual spraying, broflanilide, insecticide resistance, malaria vector control, Anopheles gambiae, Kenya","lastPublishedDoi":"10.21203/rs.3.rs-7021640/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7021640/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e\u003cp\u003eIndoor residual spraying (IRS) remains a core malaria vector control intervention, but widespread insecticide resistance threatens its effectiveness. VECTRON\u0026trade; T500, containing broflanilide, represents a novel IRS product with a new mode of action targeting GABA receptors.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eA two-arm non-inferiority study was conducted in Bar Olengo, Siaya County, Kenya, between June and November 2024. Twenty-five structures per arm were sprayed with either VECTRON\u0026trade; T500 (100mg a.i/m\u0026sup2;) or Actellic\u0026trade; 300CS (1g a.i/m\u0026sup2;), with five water-sprayed controls. Residual efficacy was assessed using WHO cone bioassays with pyrethroid-resistant \u003cem\u003eAnopheles gambiae\u003c/em\u003e s.s. Bungoma strain and susceptible Kisumu strain monthly for six months. Wild vector susceptibility to insecticides, community acceptability, and adverse events were evaluated.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eVECTRON\u0026trade; T500 maintained significantly higher mortality than Actellic\u0026trade; 300CS throughout six months on both wall types. Against resistant \u003cem\u003eAn. gambiae\u003c/em\u003e s.s. Bungoma strain, VECTRON\u0026trade; T500 achieved 98.73\u0026thinsp;\u0026plusmn;\u0026thinsp;3.51% mortality (95% CI: 97.95\u0026ndash;99.51%) compared to 80.22\u0026thinsp;\u0026plusmn;\u0026thinsp;11.23% for Actellic\u0026trade; 300CS (95% CI: 77.72\u0026ndash;82.72%; t₇₈=-10.15, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001, Cohen's d\u0026thinsp;=\u0026thinsp;2.27). For susceptible Kisumu strain, VECTRON\u0026trade; T500 maintained 100% mortality versus 89.60\u0026thinsp;\u0026plusmn;\u0026thinsp;6.34% for Actellic\u0026trade; 300CS (95% CI: 88.19\u0026ndash;91.01%; t₇₈=10.53, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001, Cohen's d\u0026thinsp;=\u0026thinsp;2.38). Actellic\u0026trade; 300CS efficacy declined below 80% after month 4, while VECTRON\u0026trade; T500 remained\u0026thinsp;\u0026gt;\u0026thinsp;95% effective throughout. Wild \u003cem\u003eAn. gambiae\u003c/em\u003e s.l. and \u003cem\u003eAn. funestus\u003c/em\u003e s.l. showed 100% susceptibility to broflanilide with no cross-resistance detected. No adverse events occurred in VECTRON\u0026trade; T500 households versus 8% (12/150) in Actellic\u0026trade; 300CS households. Community acceptance was 100% for VECTRON\u0026trade; T500 versus 99.33% (149/150) for Actellic\u0026trade; 300CS.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e\u003cp\u003eVECTRON\u0026trade; T500 demonstrated superior residual efficacy, excellent safety profile, and high community acceptance compared to Actellic\u0026trade; 300CS. Its novel mode of action and absence of cross-resistance make it valuable for insecticide resistance management in malaria vector control programs.\u003c/p\u003e","manuscriptTitle":"Community evaluation of VECTRON™ T500 (broflanilide) for indoor residual spraying for malaria vector control in Siaya county, Kenya","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-08-25 19:32:02","doi":"10.21203/rs.3.rs-7021640/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-10-06T01:07:46+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-09-06T10:42:12+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-09-01T09:52:31+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"294984224847755022353208546925384911467","date":"2025-08-20T09:58:06+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"39733753249895164263232065520677722655","date":"2025-08-18T11:35:33+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"39727390428395724242948454763725915186","date":"2025-08-18T02:39:12+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-08-17T16:39:33+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-07-02T18:17:06+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-07-02T18:15:07+00:00","index":"","fulltext":""},{"type":"submitted","content":"Malaria Journal","date":"2025-07-01T14:52:44+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"malaria-journal","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"malj","sideBox":"Learn more about [Malaria Journal](http://malariajournal.biomedcentral.com/)","snPcode":"12936","submissionUrl":"https://submission.nature.com/new-submission/12936/3","title":"Malaria Journal","twitterHandle":"@malariajournal","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"b71cf9fd-af61-485b-90d7-ccd64d417afb","owner":[],"postedDate":"August 25th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-12-01T16:16:14+00:00","versionOfRecord":{"articleIdentity":"rs-7021640","link":"https://doi.org/10.1186/s12936-025-05688-w","journal":{"identity":"malaria-journal","isVorOnly":false,"title":"Malaria Journal"},"publishedOn":"2025-11-29 15:57:38","publishedOnDateReadable":"November 29th, 2025"},"versionCreatedAt":"2025-08-25 19:32:02","video":"","vorDoi":"10.1186/s12936-025-05688-w","vorDoiUrl":"https://doi.org/10.1186/s12936-025-05688-w","workflowStages":[]},"version":"v1","identity":"rs-7021640","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7021640","identity":"rs-7021640","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}