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

Abstract

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 Olyset Plus and PermaNet 3.0 with Actellic 300CS IRS was evaluated against pyrethroid-resistant Anopheles gambiae s.l. in two parallel experimental hut trials in southern Benin. The vector population was resistant to pyrethroids and 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 pyrethroid-PBO ITNs (33–38%) 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 pyrethroid-PBO ITNs (55–59%) compared to pirimiphos-methyl IRS alone (77–78%, p < 0.001), demonstrating evidence of an antagonistic effect when both interventions are applied in the same household. Mosquito mortality in the combination was significantly higher compared to the pyrethroid-PBO ITNs alone (55–59% vs. 22–26% p < 0.001) showing potential of pirimiphos-methyl IRS to enhance vector control when deployed to complement pyrethroid-PBO ITNs in an area where PBO fails to fully restore susceptibility to pyrethroids.

PermaNet® Dual, a new deltamethrin-chlorfenapyr mixture net, shows improved efficacy against pyrethroid-resistantAnopheles gambiae sensu latoin southern Benin

“…This variability in outcome of synergist bioassays may be due to differences in the type of pyrethroid insecticide tested, test methods or seasonal changes in the vector population. However, despite complete restoration of pyrethroid susceptibility following PBO pre-exposure in bottle bioassays in this hut trial, the levels of improved mosquito mortality achieved with the PermaNet® 3.0 relative to PermaNet® 2.0 were moderate (17% vs. 40%) and did not differ substantially compared to what has been reported in previous hut studies with this vector population [20,43]. This finding would suggest the presence of more complex behavioural mechanisms that may have reduced mosquito contact with PermaNet® 3.0 compromising its efficacy in the experimental huts.…”

“…Notably, there are concerns over their durability following long-term household use [19]. Experimental hut trials in West Africa also suggest that pyrethroid-PBO ITNs may offer more limited benefits in areas with elevated pyrethroid resistance mediated by complex and multiple mechanisms [20]. More ITN types, ideally containing other novel insecticides to which vectors are susceptible are thus needed, for effective and sustainable vector control.…”

Chlorfenapyr metabolism by mosquito P450s associated with pyrethroid resistance: identification of potential activation markers.

“…Pirimiphos-methyl, an organophospate insecticide, is extensively used by malaria control programmes in Africa for indoor residual spray operations. Recent evidence from experimental hut trails in Benin indicates that PBO containing ITNs can reduce the e cacy of indoor residual spraying with Primiphos-methyl against pyrethroid-resistant malaria vectors 44 , supporting recommendations by the WHO to avoid the deployment of pyrethroid-PBO ITNs in areas that have already been programmed for IRS with pirimiphos-methyl IRS. Given that all four mosquito P450s that metabolized chlorfenapyr produced the toxic metabolite, tralopyril, and previous work has shown PBO to antagonize chlorfenapyr activity in mosquitoes 35,45 , similar recommendations are applicable to chlorfenapyr and further studies are required to determine the optimal co-deployment of products containing PBO and chlorfenapyr.…”

Can the performance of pyrethroid-chlorfenapyr nets be reduced when combined with pyrethroid-piperonyl butoxide (PBO) nets?

“…(42,43). A recent study conducted at the same experimental hut site in Benin lends credence to this hypothesis, showing reduced e cacy of pirimiphos-methyl IRS when combined with pyrethroid-PBO ITNs (44). As coverage of next-generation vector control increases, more studies like this one, investigating the impact of combining novel ITN and IRS products, are needed to inform optimal codeployment policy.…”