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

Tchouakui, Magellan; Assatse, Tatiane; Tazokong, Hervé Raoul; Oruni, Ambrose; Menze, Benjamin D.; Nguiffo-Nguete, Daniel; Mugenzi, Leon M. J.; Kayondo, Jonathan; Watsenga, Francis; Mzilahowa, Themba; Osae, Michael; Wondji, Charles S.

doi:10.21203/rs.3.rs-1677859/v1

Cited by 3 publications

(5 citation statements)

References 23 publications

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“…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). The negative association observed between the kdr-resistant marker here and IG2 e cacy indicates that this tool could help control kdr-resistant mosquitoes as observed in Benin (26).…”

Section: Discussionsupporting

confidence: 84%

“…The high e cacy of IG2 should be therefore attributed to the chlorfenapyr component in this net as reported in many African countries a full susceptibility of An. funestus to this insecticide (33). This new net having a mixture of chlorfenapyr and alphacypermethrin showed also a better e cacy compared to Interceptor ® having only alphacypermethrin and a chlorfenapyr-only net against pyrethroid-resistant An.…”

Section: Discussionmentioning

confidence: 89%

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

Tchouakui

Thiomela

Nchoutpouen³

et al. 2023

Preprint

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Background The increasing reports of resistance to pyrethroid insecticides associated with reduced efficacy of pyrethroid-only interventions highlight the urgency of introducing new non-pyrethroid-only control tools. Here, we investigated the performance of PBO-pyrethroid (PermaNet 3.0 (P3.0)) and dual active ingredients (AI) nets (Interceptor G2 (IG2) containing pyrethroids and chlorfenapyr) and Royal Guard (RG)- containing pyrethoids and pyripoxyfen) against pyrethroid-resistant malaria vectors in Cameroon.Methods The efficacy of these tools was first evaluated on Anopheles gambiae and Anopheles funestus s.s using cone/tunnel assays in five sites across the country. In addition, experimental hut trials (EHT) were performed to evaluate the performance of these nets in semi-field conditions where An funestus predominate using unwashed and 20 times washed nets. Furthermore, pyrethroid-resistant markers were genotyped in dead vs alive, blood-fed vs unfed mosquitoes after exposure to these nets to evaluate the impact of known pyrethroid resistance markers on performance of the new nets.Results IG2 was the most effective net against wild pyrethroid -resistant An funestus followed by PermaNet 3.0. In EHT, this net induced up to 87.8% (95% CI 83– 92%) mortality and 55.6% (95% CI 48– 63%) after 20 washes whilst unwashed pyrethroid-only net (Royal sentry) killed just 18% (95% CI 13–23%) of host-seeking An. funestus. The unwashed P3.0 killed up to 54% (95% CI 44–63%) of field-resistant mosquitoes and 47% (95% CI 38– 57%) when washed 20 times. IG2 and P3.0 also provided better personal protection (blood feeding inhibition 66.2% and 92.8%) compared to pyrethroid-only net RS (8.4%) RG (77.84%). Interestingly, a negative association was found between kdrW and the chlorfenapyr-based net IG2 (χ2 = 138; P < 0.0001) with RR mosquitoes predominantly found in the deadConclusions The high mortality recorded by Interceptor G2 against pyrethroid-resistant An. funestus in this study provides first field evidence of high efficacy against this major malaria vector in Cameroon. However the efficacy of this tools should be assessed in other locations and on other major malaria vectors across the country.

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Section: Discussionsupporting

confidence: 84%

Section: Discussionmentioning

confidence: 89%

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

Tchouakui

Thiomela

Nchoutpouen³

et al. 2023

Preprint

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“…funestus s.l. to this insecticide [ 37 ]. This new net having a mixture of chlorfenapyr and alphacypermethrin showed also a better efficacy compared to Interceptor ® having only alphacypermethrin and a chlorfenapyr-only net against pyrethroid-resistant An.…”

Section: Discussionmentioning

confidence: 99%

“…Such negative association noticed in this study could be attributed to the chlorfenapyr component in interceptor G2 as reported previously [ 48 ]. This insecticide is considered as pro-insecticide that is activated by oxidase enzymes suggesting a potential for negative cross-resistance [ 49 ] as shown recently that mosquitoes bearing the 1014F-resistant allele were more vulnerable to chlorfenapyr [ 37 ] and clothianidin [ 50 ]. The negative association observed between the kdr -resistant marker here and Interceptor G2 efficacy indicates that this tool could help control kdr -resistant mosquitoes as observed in Benin [ 24 ].…”

Section: Discussionmentioning

confidence: 99%

High efficacy of chlorfenapyr-based net Interceptor® G2 against pyrethroid-resistant malaria vectors from Cameroon

Tchouakui,

Thiomela,

Nchoutpouen

et al. 2023

Infect Dis Poverty

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Background The increasing reports of resistance to pyrethroid insecticides associated with reduced efficacy of pyrethroid-only interventions highlight the urgency of introducing new non-pyrethroid-only control tools. Here, we investigated the performance of piperonyl-butoxide (PBO)-pyrethroid [Permanet 3.0 (P3.0)] and dual active ingredients (AI) nets [Interceptor G2 (IG2): containing pyrethroids and chlorfenapyr and Royal Guard (RG): containing pyrethroids and pyriproxyfen] compared to pyrethroid-only net Royal Sentry (RS) against pyrethroid-resistant malaria vectors in Cameroon. Methods The efficacy of these tools was firstly evaluated on Anopheles gambiae s.l. and Anopheles funestus s.l. from Gounougou, Mibellon, Mangoum, Nkolondom, and Elende using cone/tunnel assays. In addition, experimental hut trials (EHT) were performed to evaluate the performance of unwashed and 20 times washed nets in semi-field conditions. Furthermore, pyrethroid-resistant markers were genotyped in dead vs alive, blood-fed vs unfed mosquitoes after exposure to the nets to evaluate the impact of these markers on net performance. The XLSTAT software was used to calculate the various entomological outcomes and the Chi-square test was used to compare the efficacy of various nets. The odds ratio and Fisher exact test were then used to establish the statistical significance of any association between insecticide resistance markers and bed net efficacy. Results Interceptor G2 was the most effective net against wild pyrethroid-resistant An. funestus followed by Permanet 3.0. In EHT, this net induced up to 87.8% mortality [95% confidence interval (CI): 83.5–92.1%) and 55.6% (95% CI: 48.5–62.7%) after 20 washes whilst unwashed pyrethroid-only net (Royal Sentry) killed just 18.2% (95% CI: 13.4–22.9%) of host-seeking An. funestus. The unwashed Permanet 3.0 killed up to 53.8% (95% CI: 44.3–63.4%) of field-resistant mosquitoes and 47.2% (95% CI: 37.7–56.7%) when washed 20 times, and the Royal Guard 13.2% (95% CI: 9.0–17.3%) for unwashed net and 8.5% (95% CI: 5.7–11.4%) for the 20 washed net. Interceptor G2, Permanet 3.0, and Royal Guard provided better personal protection (blood-feeding inhibition 66.2%, 77.8%, and 92.8%, respectively) compared to pyrethroid-only net Royal Sentry (8.4%). Interestingly, a negative association was found between kdrw and the chlorfenapyr-based net Interceptor G2 (χ2 = 138; P < 0.0001) with homozygote-resistant mosquitoes predominantly found in the dead ones. Conclusions The high mortality recorded with Interceptor G2 against pyrethroid-resistant malaria vectors in this study provides first semi-field evidence of high efficacy against these major malaria vectors in Cameroon encouraging the implementation of this novel net for malaria control in the country. However, the performance of this net should be established in other locations and on other major malaria vectors before implementation at a large scale. Graphical Abstract

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“…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.…”

Section: Introductionmentioning

confidence: 99%

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

Wangrawa,

Odero,

Baldini

et al. 2024

Medical Vet Entomology

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There has been significant progress in malaria control in the last 2 decades, with a decline in mortality and morbidity. However, these gains are jeopardised by insecticide resistance, which negatively impacts the core interventions, such as insecticide‐treated nets (ITN) and indoor residual spraying (IRS). While most malaria control and research efforts are still focused on Anopheles gambiae complex mosquitoes, Anopheles funestus remains an important vector in many countries and, in some cases, contributes to most of the local transmission. As countries move towards malaria elimination, it is important to ensure that all dominant vector species, including An. funestus, an important vector in some countries, are targeted. The objective of this review is to compile and discuss information related to A. funestus populations' resistance to insecticides and the mechanisms involved across Africa, emphasising the sibling species and their resistance profiles in relation to malaria elimination goals. Data on insecticide resistance in An. funestus malaria vectors in Africa were extracted from published studies. Online bibliographic databases, including Google Scholar and PubMed, were used to search for relevant studies. Articles published between 2000 and May 2023 reporting resistance of An. funestus to insecticides and associated mechanisms were included. Those reporting only bionomics were excluded. Spatial variation in species distribution and resistance to insecticides was recorded from 174 articles that met the selection criteria. It was found that An. funestus was increasingly resistant to the four classes of insecticides recommended by the World Health Organisation for malaria vector control; however, this varied by country. Insecticide resistance appears to reduce the effectiveness of vector control methods, particularly IRS and ITN. Biochemical resistance due to detoxification enzymes (P450s and glutathione‐S‐transferases [GSTs]) in An. funestus was widely recorded. However, An. funestus in Africa remains susceptible to other insecticide classes, such as organophosphates and neonicotinoids. This review highlights the increasing insecticide resistance of An. funestus mosquitoes, which are important malaria vectors in Africa, posing a significant challenge to malaria control efforts. While An. funestus has shown resistance to the recommended insecticide classes, notably pyrethroids and, in some cases, organochlorides and carbamates, it remains susceptible to other classes of insecticides such as organophosphates and neonicotinoids, providing potential alternative options for vector control strategies. The study underscores the need for targeted interventions that consider the population structure and geographical distribution of An. funestus, including its sibling species and their insecticide resistance profiles, to effectively achieve malaria elimination goals.

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

Cited by 3 publications

References 23 publications

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

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

High efficacy of chlorfenapyr-based net Interceptor® G2 against pyrethroid-resistant malaria vectors from Cameroon

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

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