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

Abstract

Background Pyrethroid-chlorfenapyr (CFP) and pyrethroid-piperonyl butoxide (PBO) nets are being scaled across endemic countries to improve control of malaria transmitted by pyrethroid-resistant mosquitoes. CFP is a pro-insecticide requiring activation by mosquito cytochrome P450 monooxygenase enzymes (P450s) while PBO improves pyrethroid potency by inhibiting the action of these enzymes in pyrethroid-resistant mosquitoes. The inhibitory action of PBO against P450s may thus reduce the efficacy of pyrethroid-CFP nets when applied inside the same household as pyrethroid-PBO nets. Methods Two experimental hut trials were performed to evaluate the entomological impact of two different types of pyrethroid-CFP ITN (Interceptor® G2, PermaNet® Dual) when applied alone and in combination with pyrethroid-PBO ITNs (DuraNet® Plus, PermaNet® 3.0) against a pyrethroid-resistant vector population in southern Benin. In both trials, all net types were tested as single and double net treatments. Bioassays were also performed to assess the resistance profile of the vector population at the hut site and investigate interactions between CFP and PBO. Results The vector population was susceptible to CFP but exhibited a high intensity of pyrethroid resistance that was overcame by PBO pre-exposure. Vector mortality was significantly lower in huts with combinations of pyrethroid-CFP nets plus pyrethroid-PBO nets compared to huts with two pyrethroid-CFP nets (74% vs. 85% for Interceptor® G2 and 57% vs. 83% for PermaNet® Dual, p < 0.001). PBO pre-exposure reduced the toxicity of CFP in bottle bioassays suggesting this effect may be partly attributable to antagonism between CFP and PBO. Higher levels of vector mortality were observed in huts with net combinations that included pyrethroid-CFP nets compared to those that did not and highest mortality was achieved when pyrethroid-CFP nets were applied alone as two nets together (83–85%). Conclusions This study shows evidence of a reduced performance of pyrethroid-CFP nets when combined with pyrethroid-PBO ITNs compared to when applied alone and higher efficacy with net combinations that included pyrethroid-CFP nets. These findings suggest that in similar contexts, prioritizing distribution of pyrethroid-CFP nets over other net types would maximize vector control impact.

TestingAnopheleslarvae and adults using standard bioassays reveals susceptibility to chlorfenapyr (pyrrole) while highlighting variability between species

“…This antagonistic effect of PBO on the efficacy of chlorfenapyr has been documented in insect pests (31,45). Chlorfenapyr is a proinsecticide whose transformation into a toxic metabolite (tralopyril) is catalysed by cytochrome P 450 enzymes (CYPs), hence the reduction in activity when CYPs are inhibited by PBO (12,13,47,48). This finding suggests that downregulation of some CYPs may be a potential mechanism Anopheles could exploit to develop resistance to chlorfenapyr as is the case in the two-spotted spider mite, Tetranychus urticae (49).…”

A descriptive review of next-generation insecticide-treated bed nets for malaria control

“…gambiae s.l., and An. funestus (Corbel et al, 2010;Ketoh et al, 2018;Oumbouke et al, 2019;Barreaux et al, 2022;Menze et al, 2022;Ngufor et al, 2022;Syme et al, 2023a;Zahouli et al, 2023). Only one study showed an increase in blood-feeding rate after PBO net exposure in Cameroon (Corbel et al, 2010), whilst no difference was seen between PBO and pITNs in Benin, Cote d'Ivoire, and Cameroon (Koudou et al, 2011;Pennetier et al, 2013;Menze et al, 2020).…”

“…gambiae s.l. from Burkina Faso, Benin, Cameroon, and Cote d'Ivoire (Bayili et al, 2017;Camara et al, 2018;Syme et al, 2023a;Tchouakui et al, 2023). One study on RG in Cameroon shows a reduced BF rate (Tchouakui et al, 2023).…”

“…gambiae s.l. in Cote d'Ivoire, Burkina Faso, Benin, and Cameroon (Bayili et al, 2017;Camara et al, 2018;Syme et al, 2023b;Syme et al, 2023a;Tchouakui et al, 2023). Differences were evident between net manufacturers, with IG2 outperforming PBO and other CFP nets (PermaNet 3.0, DuraNet Plus, and PermaNet Dual) in Cameroon and Benin (Syme et al, 2023b;Syme et al, 2023a;Tchouakui et al, 2023), whilst in Cote d'Ivoire and Benin, the use of PermaNet 3.0 and PermaNet Dual resulted in higher mortality than RG and Olyset Plus (Ngufor et al, 2022;Tchouakui et al, 2023).…”

“…Only one study showed an increase in blood-feeding rate after PBO net exposure in Cameroon (Corbel et al, 2010), whilst no difference was seen between PBO and pITNs in Benin, Cote d'Ivoire, and Cameroon (Koudou et al, 2011;Pennetier et al, 2013;Menze et al, 2020). Interestingly, a study in Benin demonstrated that PBO nets show significantly increased blood-feeding inhibition compared to CFP nets (Syme et al, 2023a). One study directly compared bloodfeeding inhibition with Olyset Plus and PermaNet 3.0 and saw no difference between the nets (Ketoh et al, 2018).…”