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 (100 mg a.i/m(2)) or Actellic™ 300CS (1 g a.i/m(2)), with five water-sprayed controls. Residual efficacy was assessed using world health organization (WHO) cone bioassays with pyrethroid-resistant Anopheles gambiae sensu stricto (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 < 0.001, Cohen's d = 2.38). Actellic™ 300CS efficacy declined below 80% after month 4, while VECTRON™ T500 remained > 95% effective throughout. Wild An. gambiae sensu lato (s.l.) and Anopheles 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, though this difference was not statistically significant. 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 to pirimiphos-methyl and pyrethroids make it valuable for insecticide resistance management in malaria vector control programmes.