Can pyrethroid-piperonyl butoxide (PBO) nets reduce the efficacy of indoor residual spraying with pirimiphos-methyl against pyrethroid-resistant malaria vectors?

As the uptake of pyrethroid-PBO ITNs increases, their combination with IRS insecticides could become an operational reality in many malaria-endemic communities. Pirimiphos-methyl is a pro-insecticide requiring activation by mosquito cytochrome P450 enzymes to induce toxicity while PBO blocks activation of these enzymes in pyrethroid-resistant vector mosquitoes. PBO may thus antagonise the toxicity of pirimiphos-methyl IRS when combined with pyrethroid-PBO ITNs. The impact of combining two major brands of pyrethroid-PBO ITNs (Olyset(R) Plus, PermaNet(R) 3.0) with pirimiphos-methyl IRS (Actellic(R) 300CS) was evaluated against pyrethroid-resistant Anopheles gambiae sl in two parallel experimental hut trials in southern Benin in comparison to bendiocarb IRS and each intervention alone. The wild vector population was resistant to pyrethroids but susceptible to pirimiphos-methyl and bendiocarb. PBO pre-exposure partially restored deltamethrin toxicity but not permethrin. Mosquito mortality in experimental huts was significantly improved in the combinations of bendiocarb IRS with Olyset(R) Plus (33%) and PermaNet(R) 3.0 (38%) compared to bendiocarb IRS alone (14-16%, p<0.001), demonstrating an additive effect. Conversely, mortality was significantly reduced in the combinations of pirimiphos-methyl IRS with Olyset(R) Plus (59%) and PermaNet(R) 3.0 (55%) compared to pirimiphos-methyl IRS alone (77-78%, p<0.001), demonstrating an antagonistic effect. Combining pirimiphos-methyl IRS with the pyrethroid-PBO ITNs provided significantly improved mosquito mortality (55-59%) compared to the pyrethroid-PBO ITNs alone (22-26%) and improved blood-feeding inhibition relative to the IRS alone. This study provided evidence of an antagonistic effect when pyrethroid-PBO ITNs were combined with pirimiphos-methyl IRS in the same household resulting in lower levels of vector mosquito mortality compared to the IRS alone. Pirimiphos-methyl IRS also showed potential to significantly enhance malaria control when deployed to complement pyrethroid-PBO ITNs in an area where PBO fails to fully restore susceptibility to pyrethroids.