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      Insecticide Resistance Associated with kdr Mutations in Aedes albopictus: An Update on Worldwide Evidences

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          Abstract

          Insecticide resistance is an increasing problem worldwide that limits the efficacy of control methods against several pests of health interest. Among them, Aedes albopictus mosquitoes are efficient vectors of relevant pathogens causing animal and human diseases worldwide, including yellow fever, chikungunya, dengue, and Zika. Different mechanisms are associated in conferring resistance to chemical insecticides. One of the most widespread and analysed mechanisms is the knockdown resistance ( kdr) causing resistance to DDT and pyrethroids. The mechanism is associated with mutations in the voltage sensitive sodium channel, which is involved in beginning and propagation of action potentials in nervous cells. The mechanism was originally discovered in the housefly and then it was found in a large number of arthropods. In 2011, a kdr associated mutation was evidenced for the first time in A. albopictus and afterward several evidences were reported in the different areas of the world, including China, USA, Brazil, India, and Mediterranean Countries. This review aims to update and summarize current evidences on kdr in A. albopictus, in order to stimulate further researches to analyse in depth A. albopictus resistance status across the world, especially in countries where the presence of this vector is still an emerging issue. Such information is currently needed given the well-known vector role of A. albopictus in the transmission of severe infectious diseases. Furthermore, the widespread use of chemical insecticides for control strategies against A. albopictus progressively lead to pressure selection inducing the rise of insecticide resistance-related mutations in the species. Such event is especially evident in some countries as China, often related to a history of uncontrolled use of chemical insecticides. Thus, a careful picture on the diffusion of kdr mutations worldwide represents a milestone for the implementation of control plans and the triggering of novel research on alternative strategies for mosquito-borne infections.

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

            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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              Identification of a point mutation in the voltage-gated sodium channel gene of Kenyan Anopheles gambiae associated with resistance to DDT and pyrethroids.

              A field trial of permethrin-impregnated bednets and curtains was initiated in Western Kenya in 1990, and a strain of Anopheles gambiae showing reduced susceptibility to permethrin was colonized from this site in 1992. A leucine-phenylalanine substitution at position 1014 of the voltage-gated sodium channel is associated with resistance to permethrin and DDT in many insect species, including Anopheles gambiae from West Africa. We cloned and sequenced a partial sodium channel cDNA from the Kenyan permethrin-resistant strain and we identified an alternative substitution (leucine to serine) at the same position, which is linked to the inheritance of permethrin resistance in the F(2) progeny of genetic crosses between susceptible and resistant individuals. The diagnostic polymerase chain reaction (PCR) developed by Martinez-Torres et al. [(1998) Insect Mol Biol 7: 179-184] to detect kdr alleles in field populations of An. gambiae will not detect the Kenyan allele and hence reliance on this assay may lead to an underestimate of the prevalence of pyrethroid resistance in this species. We adapted the diagnostic PCR to detect the leucine-serine mutation and with this diagnostic we were able to demonstrate that this kdr allele was present in individuals collected from the Kenyan trial site in 1986, prior to the introduction of pyrethroid-impregnated bednets. The An. gambiae sodium channel was physically mapped to chromosome 2L, division 20C. This position corresponds to the location of a major quantitative trait locus determining resistance to permethrin in the Kenyan strain of An. gambiae.
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                Author and article information

                Contributors
                Journal
                Biomed Res Int
                Biomed Res Int
                BMRI
                BioMed Research International
                Hindawi
                2314-6133
                2314-6141
                2018
                5 August 2018
                : 2018
                : 3098575
                Affiliations
                Laboratory of Entomology and Control of Environmental Vectors, Istituto Zooprofilattico Sperimentale della Sicilia, Via Gino Marinuzzi 3, 90129 Palermo, Italy
                Author notes

                Academic Editor: Ademir J. Martins

                Author information
                http://orcid.org/0000-0002-5609-7636
                http://orcid.org/0000-0003-0947-853X
                http://orcid.org/0000-0003-4657-407X
                Article
                10.1155/2018/3098575
                6098900
                30175124
                131dda9e-c325-4420-b0a4-720d58ccc4cd
                Copyright © 2018 Michelangelo Auteri et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 16 February 2018
                : 19 July 2018
                Funding
                Funded by: Ministero della Salute
                Award ID: RC IZS SI 16/16
                Categories
                Review Article

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