Efficacy of MiraNet Combi, a novel alpha-cypermethrin, pyriproxyfen, and piperonyl butoxide long-lasting insecticidal net against pyrethroid-resistant Anopheles funestus in western Kenya

Background The widespread use of pyrethroid-only long-lasting insecticidal nets (LLINs) has contributed substantially to malaria control; however, increasing pyrethroid resistance in malaria vectors threatens their continued effectiveness. To address this challenge, LLINs incorporating additional active ingredients have been developed. MiraNet® Combi is a novel LLIN incorporating alpha-cypermethrin, the insect growth regulator pyriproxyfen (PPF), and the synergist piperonyl butoxide (PBO). Methods We evaluated the efficacy of MiraNet® Combi against pyrethroid-resistant Anopheles funestus in western Kenya using WHO cone bioassays, tunnel tests, experimental hut trials, and chemical analysis. Non-inferiority of MiraNet® Combi to Royal Guard® (alpha-cypermethrin + PPF) and superiority to Olyset® Plus (permethrin + PBO) and MiraNet® (alpha-cypermethrin-only) were assessed for mosquito mortality and blood-feeding inhibition following 20 standardized washes, in accordance with WHO guidelines. Results In laboratory assays, MiraNet® Combi achieved high efficacy, inducing 94.5% mortality (95% CI: 91.2–97.8%) and 93.8% blood-feeding inhibition (95% CI: 90.5–97.1%) across all wash points against susceptible and resistant mosquito strains. In experimental hut trials, MiraNet® Combi produced the highest mortality, with 23% (95% CI: 21–25%) in unwashed and 25% (95% CI: 23–27%) in washed nets, significantly exceeding unwashed Olyset® Plus (19.9%, p  = 0.0002) and MiraNet® (21.9%, p  = 0.03). Blood-feeding inhibition was comparable across all ITNs (90.2–98.4%). Unwashed MiraNet® Combi reduced ovary development by 37.5% (95% CI: 32.1–42.9%), decreasing to 14.3% (95% CI: 10.2–18.4%) after washing. MiraNet® Combi was non-inferior to Royal Guard® for mosquito mortality but not for blood-feeding inhibition, superior to Olyset® Plus and MiraNet® for mosquito mortality, superior to MiraNet® for blood-feeding inhibition, and inferior to Olyset® Plus for blood-feeding inhibition. Conclusions MiraNet® Combi provides improved personal protection and enhanced efficacy against pyrethroid-resistant An. funestus compared with existing LLINs. The combination of a pyrethroid, PBO, and PPF represents a promising strategy for resistance management and malaria vector control in areas with high pyrethroid resistance.