Reduced long-lasting insecticidal net efficacy and pyrethroid insecticide resistance are associated with over-expression ofCYP6P4, CYP6P3andCYP6Z1in populations ofAnopheles coluzziifrom South-East Côte d’Ivoire

Meiwald, Anne; Clark, Emma; Kristan, Mojca; Edi, Constant; Jeffries, Claire L.; Pelloquin, Bethanie; Irish, Seth R.; Walker, Thomas; Messenger, Louisa A.

doi:10.1101/2020.09.24.311639

Cited by 5 publications

(8 citation statements)

References 40 publications

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“…Other studies in Faranah Prefecture of Guinea with 100 µg AI/bottle produced 100% mortality with wild An. gambiae s.s., while in the Agréby-Tiassa Region of south-east Côte d'Ivoire, the same concentration produced only 95.5% mortality [36,37]. Using the formula of Lees et al it was determined that 200 µg AI/bottle was a suitable discriminating concentration and this concentration is likely to produce fewer cases of false resistance reporting than with 100 µg AI/bottle.…”

Section: Discussionmentioning

confidence: 99%

Determination of the discriminating concentration of chlorfenapyr (pyrrole) and Anopheles gambiae sensu lato susceptibility testing in preparation for distribution of Interceptor® G2 insecticide-treated nets

Oxborough

Seyoum

Yihdego

et al. 2021

Malar J

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Background Following agricultural use and large-scale distribution of insecticide-treated nets (ITNs), malaria vector resistance to pyrethroids is widespread in sub-Saharan Africa. Interceptor® G2 is a new dual active ingredient (AI) ITN treated with alpha-cypermethrin and chlorfenapyr for the control of pyrethroid-resistant malaria vectors. In anticipation of these new nets being more widely distributed, testing was conducted to develop a chlorfenapyr susceptibility bioassay protocol and gather susceptibility information. Methods Bottle bioassay tests were conducted using five concentrations of chlorfenapyr at 12.5, 25, 50, 100, and 200 µg AI/bottle in 10 countries in sub-Saharan Africa using 13,639 wild-collected Anopheles gambiae sensu lato (s.l.) (56 vector populations per dose) and 4,494 pyrethroid-susceptible insectary mosquitoes from 8 colonized strains. In parallel, susceptibility tests were conducted using a provisional discriminating concentration of 100 µg AI/bottle in 16 countries using 23,422 wild-collected, pyrethroid-resistant An. gambiae s.l. (259 vector populations). Exposure time was 60 min, with mortality recorded at 24, 48 and 72 h after exposure. Results Median mortality rates (up to 72 h after exposure) of insectary colony mosquitoes was 100% at all five concentrations tested, but the lowest dose to kill all mosquitoes tested was 50 µg AI/bottle. The median 72-h mortality of wild An. gambiae s.l. in 10 countries was 71.5, 90.5, 96.5, 100, and 100% at concentrations of 12.5, 25, 50, 100, and 200 µg AI/bottle, respectively. Log-probit analysis of the five concentrations tested determined that the LC95 of wild An. gambiae s.l. was 67.9 µg AI/bottle (95% CI: 48.8–119.5). The discriminating concentration of 203.8 µg AI/bottle (95% CI: 146–359) was calculated by multiplying the LC95 by three. However, the difference in mortality between 100 and 200 µg AI/bottle was minimal and large-scale testing using 100 µg AI/bottle with wild An. gambiae s.l. in 16 countries showed that this concentration was generally suitable, with a median mortality rate of 100% at 72 h. Conclusions This study determined that 100 or 200 µg AI/bottle chlorfenapyr in bottle bioassays are suitable discriminating concentrations for monitoring susceptibility of wild An. gambiae s.l., using mortality recorded up to 72 h. Testing in 16 countries in sub-Saharan Africa demonstrated vector susceptibility to chlorfenapyr, including mosquitoes with multiple resistance mechanisms to pyrethroids.

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Section: Discussionmentioning

confidence: 99%

Determination of the discriminating concentration of chlorfenapyr (pyrrole) and Anopheles gambiae sensu lato susceptibility testing in preparation for distribution of Interceptor® G2 insecticide-treated nets

Oxborough

Seyoum

Yihdego

et al. 2021

Malar J

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“…Other studies in Faranah Prefecture of Guinea with Chlorfenapyr 100 µg AI/bottle produced 100% mortality with wild An. gambiae, while in the Agréby-Tiassa Region of southeast Côte d'Ivoire, the same concentration produced only 95.5% mortality indicating a reduced suceptibility 24,25 . In this study, when using the concentration of 100 µg AI/bottle, we detected wellestablished resistance levels in An.…”

Section: Vector Populations Exhibit a Variable Resistance Pro Le Acro...mentioning

confidence: 95%

“…Members of the An. gambiae complex were identi ed by the SINE-PCR [26,27] after genomic DNA with the Livak method [25] whereas those from An. funestus group were analysed using cocktail PCR described by Koekemoer et al 21 .…”

Section: Molecular Identi Cationmentioning

confidence: 99%

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

Tchouakui

Assatse

Tazokong

et al. 2022

Preprint

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New insecticides have recently been produced to help control pyrethroid-resistant malaria vectors including the pyrrole chlorfenapyr. Monitoring the susceptibility of mosquito populations against novel insecticides 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 100µg/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). 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 10µg/ml was observed in An funestus after to PBO, DEM and DEF whereas decreased mortality was observed in An gambiae after pre-exposure to PBO although not significant.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 the efficacy of chlorfenapyr against the widespread kdr-based pyrethroid resistance.

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“…The existence of multiple mechanisms of resistance in the main vector, Anopheles gambiae sensu lato (s.l.) threatens the efficacy of vector control tools currently used in Côte d'Ivoire, including LLINs [9][10][11]. Meiwald et al [11] found that pyrethroid resistance is associated with significant overexpression of CYP6P4, CYP6P3, and CYP6Z1 in Anopheles coluzzii in Côte d'Ivoire.…”

Section: Introductionmentioning

confidence: 99%

“…threatens the efficacy of vector control tools currently used in Côte d'Ivoire, including LLINs [9][10][11]. Meiwald et al [11] found that pyrethroid resistance is associated with significant overexpression of CYP6P4, CYP6P3, and CYP6Z1 in Anopheles coluzzii in Côte d'Ivoire. High allelic frequencies of knock-down resistance (kdr) L1014F mutation (range: 0.46-1), relatively low frequencies of the ace-1R mutation in the acetylcholinesterase gene associated with target-site insensitivity to carbamates and organophosphates (< 0.5), and elevated activity of insecticide detoxifying enzymes (mainly mixed function oxidases (MFOs), esterase and glutathione S-transferase (GST)), have been reported in Côte d'Ivoire [5,7,10].…”

Section: Introductionmentioning

confidence: 99%

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

Zahouli

Edi

Yao

et al. 2023

Malar J

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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.

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Reduced long-lasting insecticidal net efficacy and pyrethroid insecticide resistance are associated with over-expression ofCYP6P4, CYP6P3andCYP6Z1in populations ofAnopheles coluzziifrom South-East Côte d’Ivoire

Cited by 5 publications

References 40 publications

Determination of the discriminating concentration of chlorfenapyr (pyrrole) and Anopheles gambiae sensu lato susceptibility testing in preparation for distribution of Interceptor® G2 insecticide-treated nets

Determination of the discriminating concentration of chlorfenapyr (pyrrole) and Anopheles gambiae sensu lato susceptibility testing in preparation for distribution of Interceptor® G2 insecticide-treated nets

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

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

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