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      Contemporary status of insecticide resistance in the major Aedes vectors of arboviruses infecting humans

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          Abstract

          Both Aedes aegytpi and Ae. albopictus are major vectors of 5 important arboviruses (namely chikungunya virus, dengue virus, Rift Valley fever virus, yellow fever virus, and Zika virus), making these mosquitoes an important factor in the worldwide burden of infectious disease. Vector control using insecticides coupled with larval source reduction is critical to control the transmission of these viruses to humans but is threatened by the emergence of insecticide resistance. Here, we review the available evidence for the geographical distribution of insecticide resistance in these 2 major vectors worldwide and map the data collated for the 4 main classes of neurotoxic insecticide (carbamates, organochlorines, organophosphates, and pyrethroids). Emerging resistance to all 4 of these insecticide classes has been detected in the Americas, Africa, and Asia. Target-site mutations and increased insecticide detoxification have both been linked to resistance in Ae. aegypti and Ae. albopictus but more work is required to further elucidate metabolic mechanisms and develop robust diagnostic assays. Geographical distributions are provided for the mechanisms that have been shown to be important to date. Estimating insecticide resistance in unsampled locations is hampered by a lack of standardisation in the diagnostic tools used and by a lack of data in a number of regions for both resistance phenotypes and genotypes. The need for increased sampling using standard methods is critical to tackle the issue of emerging insecticide resistance threatening human health. Specifically, diagnostic doses and well-characterised susceptible strains are needed for the full range of insecticides used to control Ae. aegypti and Ae. albopictus to standardise measurement of the resistant phenotype, and calibrated diagnostic assays are needed for the major mechanisms of resistance.

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          Most cited references63

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          Molecular mechanisms of metabolic resistance to synthetic and natural xenobiotics.

          Xenobiotic resistance in insects has evolved predominantly by increasing the metabolic capability of detoxificative systems and/or reducing xenobiotic target site sensitivity. In contrast to the limited range of nucleotide changes that lead to target site insensitivity, many molecular mechanisms lead to enhancements in xenobiotic metabolism. The genomic changes that lead to amplification, overexpression, and coding sequence variation in the three major groups of genes encoding metabolic enzymes, i.e., cytochrome P450 monooxygenases (P450s), esterases, and glutathione-S-transferases (GSTs), are the focus of this review. A substantial number of the adaptive genomic changes associated with insecticide resistance that have been characterized to date are transposon mediated. Several lines of evidence suggest that P450 genes involved in insecticide resistance, and perhaps insecticide detoxification genes in general, may share an evolutionary association with genes involved in allelochemical metabolism. Differences in the selective regime imposed by allelochemicals and insecticides may account for the relative importance of regulatory or structural mutations in conferring resistance.
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            The molecular basis of insecticide resistance in mosquitoes.

            Insecticide resistance is an inherited characteristic involving changes in one or more insect gene. The molecular basis of these changes are only now being fully determined, aided by the availability of the Drosophila melanogaster and Anopheles gambiae genome sequences. This paper reviews what is currently known about insecticide resistance conferred by metabolic or target site changes in mosquitoes.
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              The unique mutation in ace-1 giving high insecticide resistance is easily detectable in mosquito vectors.

              High insecticide resistance resulting from insensitive acetylcholinesterase (AChE) has emerged in mosquitoes. A single mutation (G119S of the ace-1 gene) explains this high resistance in Culex pipiens and in Anopheles gambiae. In order to provide better documentation of the ace-1 gene and the effect of the G119S mutation, we present a three-dimension structure model of AChE, showing that this unique substitution is localized in the oxyanion hole, explaining the insecticide insensitivity and its interference with the enzyme catalytic functions. As the G119S creates a restriction site, a simple PCR test was devised to detect its presence in both A. gambiae and C. pipiens, two mosquito species belonging to different subfamilies (Culicinae and Anophelinae). It is possibile that this mutation also explains the high resistance found in other mosquitoes, and the present results indicate that the PCR test detects the G119S mutation in the malaria vector A. albimanus. The G119S has thus occurred independently at least four times in mosquitoes and this PCR test is probably of broad applicability within the Culicidae family.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS Negl Trop Dis
                PLoS Negl Trop Dis
                plos
                plosntds
                PLoS Neglected Tropical Diseases
                Public Library of Science (San Francisco, CA USA )
                1935-2727
                1935-2735
                20 July 2017
                July 2017
                : 11
                : 7
                : e0005625
                Affiliations
                [1 ] Oxford Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, United Kingdom
                [2 ] Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology-Hellas, Heraklion, Greece
                [3 ] Department of Crop Science, Pesticide Science Lab, Agricultural University of Athens, Athens, Greece
                [4 ] Laboratório de Fisiologia e Controle de Artrópodes Vetores, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz (FIOCRUZ), Manguinhos, Rio de Janeiro, Rio de Janeiro, Brazil
                [5 ] Environmental Health Institute, National Environment Agency, Helios Block, Singapore
                [6 ] Unité d'Entomologie Médicale, Institut Pasteur de la Guyane, Cayenne, French Guiana
                [7 ] Insecticides and Insecticide Resistance Lab, National Institute of Malaria Research (ICMR), Delhi, India
                [8 ] Global Health and Tropical Medicine (GHTM), Instituto de Higiene e Medicina Tropical (IHMT), Universidade Nova de Lisboa (UNL), Lisbon, Portugal
                [9 ] Institut de Recherche pour le Développement (IRD), Maladies Infectieuses et Vecteurs, Ecologie, Génétique, Evolution et Contrôle (MIVEGEC), Montpellier, France
                [10 ] Laboratoire d'Ecologie Alpine (LECA), Centre National de la Recherche Scientifique (CNRS), University Grenoble-Alpes (UGA), Grenoble, France
                [11 ] Department of Vector Biology, Liverpool School of Tropical Medicine, Liverpool, United Kingdom
                Johns Hopkins Bloomberg School of Public Health, UNITED STATES
                Author notes

                The authors have declared that no competing interests exist.

                Author information
                http://orcid.org/0000-0002-8028-4079
                Article
                PNTD-D-17-00323
                10.1371/journal.pntd.0005625
                5518996
                28727779
                48c14f5d-b7a3-4f06-b29f-62a915c5db54
                © 2017 Moyes et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                Page count
                Figures: 6, Tables: 2, Pages: 20
                Funding
                The preparation of this review was funded by an award from the World Health Organization's Special Programme for Research and Training in Tropical Diseases ( http://www.who.int/tdr/) to VC, JPD, and the WIN network. The bioassay data extraction was funded by Wellcome Trust ( https://wellcome.ac.uk/) grant 108440/Z/15/Z awarded to CLM. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Review
                Biology and Life Sciences
                Agriculture
                Agrochemicals
                Insecticides
                Medicine and Health Sciences
                Infectious Diseases
                Disease Vectors
                Insect Vectors
                Mosquitoes
                Aedes Aegypti
                Biology and Life Sciences
                Species Interactions
                Disease Vectors
                Insect Vectors
                Mosquitoes
                Aedes Aegypti
                Biology and Life Sciences
                Organisms
                Animals
                Invertebrates
                Arthropoda
                Insects
                Mosquitoes
                Aedes Aegypti
                Biology and Life Sciences
                Population Biology
                Population Dynamics
                Geographic Distribution
                Medicine and Health Sciences
                Infectious Diseases
                Disease Vectors
                Insect Vectors
                Mosquitoes
                Biology and Life Sciences
                Species Interactions
                Disease Vectors
                Insect Vectors
                Mosquitoes
                Biology and Life Sciences
                Organisms
                Animals
                Invertebrates
                Arthropoda
                Insects
                Mosquitoes
                Physical Sciences
                Chemistry
                Chemical Compounds
                Organic Compounds
                Ethers
                Organophosphates
                Physical Sciences
                Chemistry
                Organic Chemistry
                Organic Compounds
                Ethers
                Organophosphates
                Medicine and Health Sciences
                Infectious Diseases
                Disease Vectors
                Insect Vectors
                Biology and Life Sciences
                Species Interactions
                Disease Vectors
                Insect Vectors
                Biology and Life Sciences
                Biochemistry
                Enzymology
                Enzyme Chemistry
                Enzyme Metabolism
                Biology and Life Sciences
                Genetics
                Gene Identification and Analysis
                Mutation Detection

                Infectious disease & Microbiology
                Infectious disease & Microbiology

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