Detection of a reduced susceptibility to chlorfenapyr in the malaria vector Anopheles gambiae contrasts with full susceptibility in Anopheles funestus across Africa

Abstract

New insecticides have recently been produced to help control pyrethroid-resistant malaria vectors including the pyrrole, chlorfenapyr. Monitoring the susceptibility of mosquito populations against this new product and potential cross-resistance with current insecticides is vital for better resistance management. In this study, we assessed the resistance status of the major malaria vectors Anopheles gambiae and Anopheles funestus to chlorfenapyr across Africa and explored potential cross-resistance with known pyrethroid resistance markers. Efficacy of chlorfenapyr 100 µg/ml against An. gambiae and An. funestus from five Cameroonian locations, the Democratic Republic of Congo, Ghana, Uganda, and Malawi was assessed using CDC bottle assays. Synergist assays were performed with PBO (4%), DEM (8%) and DEF (0.25%) and several pyrethroid-resistant markers were genotyped in both species to assess potential cross-resistance between pyrethroids and chlorfenapyr. Resistance to chlorfenapyr was detected in An. gambiae populations from DRC (Kinshasa) (mortality rate: 64.3 ± 7.1%) Ghana (Obuasi) (65.9 ± 7.4%), Cameroon (Mangoum; 75.2 ± 7.7% and Nkolondom; 86.1 ± 7.4). In contrast, all An. funestus populations were fully susceptible. A negative association was observed between the L1014F-kdr mutation and chlorfenapyr resistance with a greater frequency of homozygote resistant mosquitoes among the dead mosquitoes after exposure compared to alive (OR 0.5; P = 0.02) whereas no association was found between GSTe2 (I114T in An. gambiae; L119F in An. funestus) and resistance to chlorfenapyr. A significant increase of mortality to chlorfenapyr 10 µg/ml was observed in An. funestus after to PBO, DEM and DEF whereas a trend for a decreased mortality was observed in An. gambiae after PBO pre-exposure. This study reveals a greater risk of chlorfenapyr resistance in An. gambiae populations than in An. funestus. However, the higher susceptibility in kdr-resistant mosquitoes points to higher efficacy of chlorfenapyr against the widespread kdr-based pyrethroid resistance.

A Chlorfenapyr-Based Net Interceptor® G2 Shows High Efficacy Against a Pyrethroid Resistant Anopheles funestus from Central Cameroon

“…L1014F-kdr mutation is negatively associated with resistance to IG2 whereas the L119F-GSTe2 mutation has no major impact In this study, a negative association was found between the kdrw mutation and mosquitoes' ability to survive exposure to the chlorfenapyr-based net IG2 (χ2 = 138; P < 0.0001) with RR mosquitoes most found in the dead. Such negative association noticed in this study could be attributed to the chlorfenapyr component in interceptor G2 as reported previously (44). This insecticide is considered as pro-insecticide that is activated by oxidase enzymes suggesting a potential for negative cross-resistance (45) as shown recently that mosquitoes bearing the 1014F-resistant allele were more vulnerable to chlorfenapyr (33) and clothianidin (46).…”

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

“…While the P450s identi ed by our screening results may be considered to be activating markers of chlorfenapyr activity, reduced susceptibility in some pyrethroid resistant populations in DRC, Ghana and Cameroon has been reported 42 . The reasons for the reduced susceptibility are unclear, but given the multiplicity of P450's present in mosquito genomes (> 100), it is feasible that detoxi cation by other P450s may be a factor.…”

Distribution and insecticide resistance profile of the major malaria vectorAnopheles funestusgroup across theAfricancontinent

“…Since then, several studies have been conducted in sub‐Saharan Africa to distinguish An. funestus group species and assess their susceptibility to commonly used insecticides (Dia et al, 2013; Tchouakui et al, 2023). The resistance of An.…”

“…gambiae, An. funestus resistance to insecticides has been less extensively investigated, though there is now evidence of resistance to the multiple classes of insecticides (Coetzee & Koekemoer, 2013;Knox et al, 2014) with the exception of chlorfenapyr (Tchouakui et al, 2022(Tchouakui et al, , 2023 and the neonicotinoid clothianidin, which was recently prequalified by World Health Organisation (WHO) for IRS (Fouet et al, 2020). In West Africa, An.…”