Control of pyrethroid-resistant Anopheles gambiae s.l. with Sovrenta® 15WP, a new isoxazoline insecticide for indoor residual spraying

Introduction: An expanded portfolio of more effective WHO-prequalified insecticides for indoor residual sparing (IRS) is needed to provide additional options to disease control programmes and enhance their capacity to efficiently apply IRS rotations for managing vector resistance to insecticides. We investigated the efficacy and residual activity of Sovrenta® 15WP, a wettable powder formulation of the newly discovered isoxazoline insecticide isocycloseram, (active ingredient trademarked as PLINAZOLIN® technology) for IRS in laboratory bioassays and experimental hut studies. Methods: Sovrenta® 15WP, was evaluated under laboratory conditions for 12 months at the dose of 120 mg a.i./m ² on cement, mud and wood block substrates against insecticide-susceptible Anopheles gambiae sensu stricto Kisumu and pyrethroid-resistant An. gambiae sensu lato (s.l.) Covè strains. An experimental hut trial was also performed to investigate its efficacy and residual activity on cement and mud-plastered walls at the target dose of 120 mg a.i./m ² over 12 months against wild free-flying pyrethroid-resistant An. gambiae sl at the Covè experimental hut station in Benin. Mosquito mortality was recorded every 24h for up to 168h post-exposure. Sovrenta® 15 WP was compared to Actellic® 300CS, a WHO/PQ-listed pirimiphos-methyl IRS insecticide applied at 1000 mg a.i./m ² . Results: In laboratory cone bioassays, Sovrenta® 15WP induced >80% mortality of susceptible and pyrethroid-resistant An. gambiae sl for 11-12 months on cement, mud and wood block substrates. A total of 12,850 wild pyrethroid-resistant An. gambiae s.l. were collected in the experimental hut trial. Sovrenta® 15WP induced significantly higher mosquito mortality in the experimental huts over 12 months compared to Actellic® 300CS (68-72% vs 44-46%, p<0.001). The insecticide also demonstrated a delayed mortality effect against wild vector mosquitoes that increased gradually from 25-42% at 24h to 68-72% at 168h post-exposure. Vector mortality did not differ substantially between the different substrate types. The odds ratio describing the difference in overall mortality between Actellic® 300CS and Sovrenta® 15WP was 3.38 (95% CI: 2.90 - 3.94) in cement-walled huts, 2.49 (95% CI: 2.10 – 2.95) in mud-walled huts and 1.80 (95% CI:1.53 – 2.11) when data for both hut wall substrate types was combined. Using recent WHO guidelines for determining non-inferiority, Sovrenta® 15WP was non-inferior and superior to Actellic® 300CS for the primary end-point of mosquito mortality over the 12-month experimental hut trial. Mortality in in situ hut wall cone bioassays was >80% for 12 months with Sovrenta® 15WP and 9 months with Actellic® 300CS. Conclusion: Sovrenta® 15WP provided extended control of pyrethroid-resistant malaria vectors when applied for IRS on local wall substrates. The insecticide presents a new effective IRS option for achieving improved malaria control and managing insecticide resistance through the rotation of IRS insecticides.