Small-scale field evaluation of PermaNet® Dual (a long-lasting net coated with a mixture of chlorfenapyr and deltamethrin) against pyrethroid-resistant Anopheles gambiae mosquitoes from Tiassalé, Côte d’Ivoire

Abstract

Background Due to the rapid expansion of pyrethroid-resistance in malaria vectors in Africa, Global Plan for Insecticide Resistance Management (GPIRM) has recommended the development of long-lasting insecticidal nets (LLINs), containing insecticide mixtures of active ingredients with different modes of action to mitigate resistance and improve LLIN efficacy. This good laboratory practice (GLP) study evaluated the efficacy of the chlorfenapyr and deltamethrin-coated PermaNet® Dual, in comparison with the deltamethrin and synergist piperonyl butoxide (PBO)-treated PermaNet® 3.0 and the deltamethrin-coated PermaNet® 2.0, against wild free-flying pyrethroid-resistant Anopheles gambiae sensu lato (s.l.), in experimental huts in Tiassalé, Côte d’Ivoire (West Africa). Methods PermaNet® Dual, PermaNet® 3.0 and PermaNet® 2.0, unwashed and washed (20 washes), were tested against free-flying pyrethroid-resistant An. gambiae s.l. in the experimental huts in Tiassalé, Côte d’Ivoire from March to August 2020. Complementary laboratory cone bioassays (daytime and 3-min exposure) and tunnel tests (nightly and 15-h exposure) were performed against pyrethroid-susceptible An. gambiae sensu stricto (s.s.) (Kisumu strain) and pyrethroid-resistant An. gambiae s.l. (Tiassalé strain). Results PermaNet® Dual demonstrated significantly improved efficacy, compared to PermaNet® 3.0 and PermaNet® 2.0, against the pyrethroid-resistant An. gambiae s.l. Indeed, the experimental hut trial data showed that the mortality and blood-feeding inhibition in the wild pyrethroid-resistant An. gambiae s.l. were overall significantly higher with PermaNet® Dual compared with PermaNet® 3.0 and PermaNet® 2.0, for both unwashed and washed samples. The mortality with unwashed and washed samples were 93.6 ± 0.2% and 83.2 ± 0.9% for PermaNet® Dual, 37.5 ± 2.9% and 14.4 ± 3.9% for PermaNet® 3.0, and 7.4 ± 5.1% and 11.7 ± 3.4% for PermaNet® 2.0, respectively. Moreover, unwashed and washed samples produced the respective percentage blood-feeding inhibition of 41.4 ± 6.9% and 43.7 ± 4.8% with PermaNet® Dual, 51.0 ± 5.7% and 9.8 ± 3.6% with PermaNet® 3.0, and 12.8 ± 4.3% and − 13.0 ± 3.6% with PermaNet® 2.0. Overall, PermaNet® Dual also induced higher or similar deterrence, exophily and personal protection when compared with the standard PermaNet® 3.0 and PermaNet® 2.0 reference nets, with both unwashed and washed net samples. In contrast to cone bioassays, tunnel tests predicted the efficacy of PermaNet® Dual seen in the current experimental hut trial. Conclusion The deltamethrin-chlorfenapyr-coated PermaNet® Dual induced a high efficacy and performed better than the deltamethrin-PBO PermaNet® 3.0 and the deltamethrin-only PermaNet® 2.0, testing both unwashed and 20 times washed samples against the pyrethroid-susceptible and resistant strains of An. gambiae s.l. The inclusion of chlorfenapyr with deltamethrin in PermaNet® Dual net greatly improved protection and control of pyrethroid-resistant An. gambiae populations. PermaNet® Dual thus represents a promising tool, with a high potential to reduce malaria transmission and provide community protection in areas compromised by mosquito vector resistance to pyrethroids.

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

“…In contrast, we observed markedly improved mortality rates with both types of pyrethroid-CFP ITN compared to pyrethroid-PBO and pyrethroid-only ITNs which can be attributed to the susceptibility of the Covè vector population to CFP. The superiority of pyrethroid-CFP ITNs over other ITN types is supported by recent experimental hut trials (29,34,35,36) and cRCTs in Benin (37) and Tanzania (14), and was formally acknowledged in recently revised WHO guidelines recommending them over pyrethroid-only and pyrethroid-PBO ITNs (10).…”

Laboratory evaluation of the regeneration time, efficacy and wash-resistance of PermaNet® Dual (a deltamethrin-chlorfenapyr net) against susceptible and pyrethroid-resistant strains ofAnopheles gambiae

“…The comparable performance of PermaNet® Dual and Interceptor® G2 against pyrethroid-resistant mosquitoes is consistent with a recent experimental hut trial in Benin which demonstrated the non-inferiority of PermaNet® Dual to Interceptor® G2 against wild, pyrethroid-resistant mosquitoes (30). Based on this and similar evidence of efficacy from trials in Côte d’Ivoire (31) and Kenya (22), PermaNet® Dual was added to the WHO list of prequalified vector control products (17) and included in the recent policy recommendation for pyrethroid-CFP ITNs (22). The findings of the present study reaffirm that PermaNet® Dual performs similarly to the first-in-class pyrethroid-CFP ITN Interceptor® G2 and represents an additional option of this highly effective net class for control of malaria transmitted by pyrethroid-resistant mosquitoes.…”

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

“…aegypti (Merida, Mexico) 36 , while dual action bed nets containing pyrethroids a-cypermethrin or deltamethrin and chlorfenapyr have proven more effective against pyrethroid resistant An. gambiae in Burkina-Faso and cote d'Ivoire respectively 7,37 , where elevated levels of CYP6P3 are reported 38,39 Early studies have also indicated that chlorfenapyr appears to be more toxic to pyrethroid resistant pests such as the cattle horn y, or the tobacco budworm where pyrethroid resistance is based on elevated P450 activity 40,41 . However, caution must be applied in correlating metabolic pyrethroid resistance with chlorfenapyr activation given that only four of the nine P450s tested were capable of metabolizing chlorfenapyr and rates of metabolism differed widely.…”