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An Experimental Hut Evaluation of PBO-Based and Pyrethroid-Only Nets against the Malaria Vector Anopheles funestus Reveals a Loss of Bed Nets Efficacy Associated with GSTe2 Metabolic Resistance

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Vector Biology Department, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK
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Centre for Research in Infectious Diseases (CRID), LSTM Research Unit, Yaoundé 13591, Cameroon
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Faculty of Sciences, University of Yaoundé I, Yaoundé 337, Cameroon
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Centre Suisse de Recherches scientifiques (CSRS), Yopougon 1303, Abidjan, Cote d’ivoire
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Syngenta UK Limited, CPC4 Capital Park, Fulbourn, Cambridgeshire CB21 5XE, UK
*
Authors to whom correspondence should be addressed.
Genes 2020, 11(2), 143; https://doi.org/10.3390/genes11020143
Received: 28 October 2019 / Revised: 14 December 2019 / Accepted: 16 December 2019 / Published: 29 January 2020
(This article belongs to the Section Animal Genetics and Genomics)
Growing insecticide resistance in malaria vectors is threatening the effectiveness of insecticide-based interventions, including Long Lasting Insecticidal Nets (LLINs). However, the impact of metabolic resistance on the effectiveness of these tools remains poorly characterized. Using experimental hut trials and genotyping of a glutathione S-transferase resistance marker (L119F-GSTe2), we established that GST-mediated resistance is reducing the efficacy of LLINs against Anopheles funestus. Hut trials performed in Cameroon revealed that Piperonyl butoxide (PBO)-based nets induced a significantly higher mortality against pyrethroid resistant An. funestus than pyrethroid-only nets. Blood feeding rate and deterrence were significantly higher in all LLINs than control. Genotyping the L119F-GSTe2 mutation revealed that, for permethrin-based nets, 119F-GSTe2 resistant mosquitoes have a greater ability to blood feed than susceptible while the opposite effect is observed for deltamethrin-based nets. For Olyset Plus, a significant association with exophily was observed in resistant mosquitoes (OR = 11.7; p < 0.01). Furthermore, GSTe2-resistant mosquitoes (cone assays) significantly survived with PermaNet 2.0 (OR = 2.1; p < 0.01) and PermaNet 3.0 (side) (OR = 30.1; p < 0.001) but not for Olyset Plus. This study shows that the efficacy of PBO-based nets (e.g., blood feeding inhibition) against pyrethroid resistant malaria vectors could be impacted by other mechanisms including GST-mediated metabolic resistance not affected by the synergistic action of PBO. Mosaic LLINs incorporating a GST inhibitor (diethyl maleate) could help improve their efficacy in areas of GST-mediated resistance. View Full-Text
Keywords: malaria; Long Lasting Insecticidal Nets; insecticide resistance; metabolic resistance; glutathione S-transferase; Anopheles funestus; piperonyl butoxide malaria; Long Lasting Insecticidal Nets; insecticide resistance; metabolic resistance; glutathione S-transferase; Anopheles funestus; piperonyl butoxide
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Menze, B.D.; Kouamo, M.F.; Wondji, M.J.; Tchapga, W.; Tchoupo, M.; Kusimo, M.O.; Mouhamadou, C.S.; Riveron, J.M.; Wondji, C.S. An Experimental Hut Evaluation of PBO-Based and Pyrethroid-Only Nets against the Malaria Vector Anopheles funestus Reveals a Loss of Bed Nets Efficacy Associated with GSTe2 Metabolic Resistance. Genes 2020, 11, 143.

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