Community evaluation of VECTRONTM T500, a broflanilide insecticide, for indoor residual spraying for malaria vector control in Central Benin; a two arm non-inferiority cluster randomised trial
Authors: Ngufor Corine , Govoetchan Renaud , Fongnikin Augustin , Hueha Corneille , Ahoga Juniace , Syme Thomas , Agbevo Abel , Daleb Abdoulaye , Small Graham , Nimmo Derric , Bradley John , Aikpon Rock , Iyikirenga Laurent , Osse Razaki , Tokponon Filemon , Padonou Germain Gil 
Published: July 2023

Abstract
Background: VECTRONTM T500 is a wettable powder IRS formulation of broflanilide, a newly discovered insecticide. We performed a two-arm non-inferiority community randomised evaluation of VECTRONTM T500, compared to Fludora® Fusion against pyrethroid-resistant Anopheles gambiae s.l. in an area of high coverage with pyrethroid-only nets in the Za-Kpota District of Central Benin.
Method: One round of IRS was applied in all consenting households in the study area. Sixteen clusters were randomised (1:1) to receive VECTRONTM T500 (100 mg/m² for broflanilide) or Fludora® Fusion (200 mg/m² for clothianidin and 25 mg/m² for deltamethrin). Surveys were performed to assess adverse events and the operational feasibility and acceptability of VECTRONTM T500 among spray operators and household inhabitants. Human landing catches were conducted in 6 households every 1-2 months for up to 18 months post-intervention to assess the impact on vector densities, sporozoite rates and entomological inoculation rates. Bottle bioassays were performed to monitor vector susceptibility to pyrethroids, broflanilide and clothianidin. Monthly wall cone bioassays were conducted for 24 months to assess the residual efficacy of the IRS formulations using susceptible and pyrethroid-resistant An. gambiae s.l.
Results: A total of 26,562 female mosquitoes were collected during the study, of which 40% were An. gambiae s.l., the main malaria vector in the study area. The vector population showed high intensity pyrethroid resistance but was susceptible to broflanilide (6 µg/bottle) and clothianidin (90 µg/bottle). Using a non-inferiority margin of 50%, vector density indicated by the human biting rate (bites/person/night) was non-inferior in the VECTRONTM T500 arm compared to the Fludora® Fusion arm both indoors (0.846 bites/p/n in Fludora® Fusion arm vs. 0.741 bites/p/n in VECTRONTM T500 arm, IRR = 0.54, 95% CI 0.22-1.35, p=0.150) and outdoors (0.691 bites/p/n in Fludora® Fusion arm vs. 0.590 bites/p/n in VECTRONTM T500 clusters, IRR = 0.75, 95% CI 0.41-1.38, p=0.297). Sporozoite rates and entomological inoculation rates did not differ significantly between study arms (sporozoite rate: 0.9% vs 1.1%, p = 0. 0.746, EIR: 0.008 vs 0.006 infective bites per person per night, p=0.589). Cone bioassay mortality with both VECTRONTM T500 and Fludora® Fusion was 100% for 24 months post-IRS application on both cement and mud treated house walls with both susceptible and pyrethroid-resistant strains of An. gambiae s.l. Perceived adverse events reported by spray operators and householders were generally very low (<6%) in both study arms.
Conclusions: VECTRONTM T500 was non-inferior to Fludora® Fusion in reducing the risk of malaria transmission by pyrethroid resistant vectors when applied for IRS in communities in Central Benin. The insecticide showed prolonged residual efficacy on house walls, lasting over 24 months and had a high acceptability with homeowners. Community application of VECTRONTM T500 for IRS provides improved and prolonged control of pyrethroid resistant malaria vectors and enhances our capacity to manage insecticide resistance.