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      Contributions of cuticle permeability and enzyme detoxification to pyrethroid resistance in the major malaria vector Anopheles gambiae

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          Abstract

          To tackle the problem of insecticide resistance, all resistance mechanisms need to be studied. This study investigated the involvement of the cuticle in pyrethroid resistance in a strain of Anopheles gambiae, MRS, free of kdr mutations. Bioassays revealed MRS to be resistant to pyrethroids and DDT, indicated by increasing knockdown times and resistance ratios. Moreover, biochemical analysis indicated that metabolic resistance based on enhanced CYP450 activity may also play a role. Insecticide penetration assays showed that there were significantly lower amounts of insecticide in the MRS strain than in the susceptible control. Analysis of the levels of the selected transcripts by qPCR showed that CYP6M2, a major pyrethroid metaboliser, CYP4G16, a gene implicated in resistance via its contribution to the biosynthesis of elevated epicuticular hydrocarbons that delay insecticide uptake, and the cuticle genes CPAP3-E and CPLCX1 were upregulated after insecticide exposure. Other metabolic (CYP6P3, GSTe2) and cuticle (CPLCG3, CPRs) genes were also constitutively upregulated. Microscopic analysis showed that the cuticle layers of the MRS strain were significantly thicker than those of the susceptible strain. This study allowed us to assess the contribution made by the cuticle and metabolic mechanisms to pyrethroid resistance in Anopheles gambiae without target-site mutations.

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          Pyrethroid resistance in African anopheline mosquitoes: what are the implications for malaria control?

          The use of pyrethroid insecticides in malaria vector control has increased dramatically in the past decade through the scale up of insecticide treated net distribution programmes and indoor residual spraying campaigns. Inevitably, the major malaria vectors have developed resistance to these insecticides and the resistance alleles are spreading at an exceptionally rapid rate throughout Africa. Although substantial progress has been made on understanding the causes of pyrethroid resistance, remarkably few studies have focused on the epidemiological impact of resistance on current malaria control activities. As we move into the malaria eradication era, it is vital that the implications of insecticide resistance are understood and strategies to mitigate these effects are implemented. Copyright © 2010 Elsevier Ltd. All rights reserved.
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            Ecological, behavioral, and biochemical aspects of insect hydrocarbons.

            This review covers selected literature from 1982 to the present on some of the ecological, behavioral, and biochemical aspects of hydrocarbon use by insects and other arthropods. Major ecological and behavioral topics are species- and gender-recognition, nestmate recognition, task-specific cues, dominance and fertility cues, chemical mimicry, and primer pheromones. Major biochemical topics include chain length regulation, mechanism of hydrocarbon formation, timing of hydrocarbon synthesis and transport, and biosynthesis of volatile hydrocarbon pheromones of Lepidoptera and Coleoptera. In addition, a section is devoted to future research needs in this rapidly growing area of science.
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              Changes in Anopheles funestus biting behavior following universal coverage of long-lasting insecticidal nets in Benin.

              Behavioral modification of malaria vectors in response to vector control methods is of great concern. We investigated whether full coverage of long-lasting insecticide-treated mosquito nets (LLINs) may induce a switch in biting behavior in Anopheles funestus, a major malaria vector in Africa. Human-landing collections were conducted indoor and outdoor in 2 villages (Lokohouè and Tokoli) in Benin before and 1 year and 3 years after implementation of universal LLIN coverage. Proportion of outdoor biting (POB) and median catching times (MCT) were compared. The resistance of A. funestus to deltamethrin was monitored using bioassays. MCT of A. funestus switched from 2 AM in Lokohoué and 3 AM in Tokoli to 5 AM after 3 years (Mann-Whitney U test, P < .0001). In Tokoli, POB increased from 45% to 68.1% (odds ratio = 2.55; 95 confidence interval = 1.72-3.78; P < .0001) 1 year after the universal coverage, whereas POB was unchanged in Lokohoué. In Lokohoué, however, the proportion of A. funestus that bites after 6 am was 26%. Bioassays showed no resistance to deltamethrin. This study provides evidence for a switch in malaria vectors' biting behavior after the implementation of LLIN at universal coverage. These findings might have direct consequences for malaria control in Africa and highlighted the need for alternative strategies for better targeting malaria vectors.
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                Author and article information

                Contributors
                gildasy@gmail.com
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                11 September 2017
                11 September 2017
                2017
                : 7
                : 11091
                Affiliations
                [1 ]ISNI 0000000122879528, GRID grid.4399.7, Institut de Recherche pour le Développement (IRD), Maladies Infectieuses et Vecteurs: Ecologie, Génétique, Evolution et Contrôle (MIVEGEC), ; UMR - IRD224, CNRS 5290 Montpellier, France
                [2 ]ISNI 0000 0004 0635 685X, GRID grid.4834.b, Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology-Hellas, ; Heraklion, 70013 Greece
                [3 ]ISNI 0000 0004 0576 3437, GRID grid.8127.c, Department of Biology, , University of Crete, ; Vassilika Vouton, Heraklion, 70013 Greece
                [4 ]Walloon Agricultural Research Centre (CRA-W), Agriculture and Natural Environment Department (D3), Plant Protection Products and Biocides, Physico-chemistry and Residues Unit (U10), B-5030 Gembloux, Belgium
                Article
                11357
                10.1038/s41598-017-11357-z
                5593880
                28894186
                10039cae-253f-4d49-a6bc-22405fd5b6d9
                © The Author(s) 2017

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 31 May 2017
                : 18 August 2017
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