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      Systemically and cutaneously distributed ectoparasiticides: a review of the efficacy against ticks and fleas on dogs

      review-article
      1 , , 2
      Parasites & Vectors
      BioMed Central
      Ectoparasiticide, Acaricide, Insecticide, Permethrin, Fluralaner, Dog

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          Abstract

          Acaricidal (tick) and insecticidal (flea) efficacy of systemically and cutaneously distributed ectoparasiticide products for dogs are compared based on permethrin and fluralaner as representative molecules. Results of efficacy studies against fleas and ticks are reviewed that show generally good to excellent results. Both externally and systemically distributed treatments have benefits and weaknesses in potentially preventing pathogen transmission by these arthropod vectors.

          Four general properties are considered related to the goal of providing optimal reduction in the risk of vector-borne pathogen transmission. These are:

          1. Owner adherence to the recommended treatment protocol;

          2. Rapid onset of activity following administration;

          3. Uniform efficacy over all areas of the treated dog at risk for parasite attachment;

          4. Maintenance of high efficacy throughout the retreatment interval.

          In considering these four factors, a systemically distributed acaricide can offer an option that is at least as effective as a cutaneously administered acaricide with regard to the overall goal of reducing the risk of vector-borne pathogen transmission.

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          Most cited references84

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          The novel isoxazoline ectoparasiticide fluralaner: selective inhibition of arthropod γ-aminobutyric acid- and L-glutamate-gated chloride channels and insecticidal/acaricidal activity.

          Isoxazolines are a novel class of parasiticides that are potent inhibitors of γ-aminobutyric acid (GABA)-gated chloride channels (GABACls) and L-glutamate-gated chloride channels (GluCls). In this study, the effects of the isoxazoline drug fluralaner on insect and acarid GABACl (RDL) and GluCl and its parasiticidal potency were investigated. We report the identification and cDNA cloning of Rhipicephalus (R.) microplus RDL and GluCl genes, and their functional expression in Xenopus laevis oocytes. The generation of six clonal HEK293 cell lines expressing Rhipicephalus microplus RDL and GluCl, Ctenocephalides felis RDL-A285 and RDL-S285, as well as Drosophila melanogaster RDLCl-A302 and RDL-S302, combined with the development of a membrane potential fluorescence dye assay allowed the comparison of ion channel inhibition by fluralaner with that of established insecticides addressing RDL and GluCl as targets. In these assays fluralaner was several orders of magnitude more potent than picrotoxinin and dieldrin, and performed 5-236 fold better than fipronil on the arthropod RDLs, while a rat GABACl remained unaffected. Comparative studies showed that R. microplus RDL is 52-fold more sensitive than R. microplus GluCl to fluralaner inhibition, confirming that the GABA-gated chloride channel is the primary target of this new parasiticide. In agreement with the superior RDL on-target activity, fluralaner outperformed dieldrin and fipronil in insecticidal screens on cat fleas (Ctenocephalides felis), yellow fever mosquito larvae (Aedes aegypti) and sheep blowfly larvae (Lucilia cuprina), as well as in acaricidal screens on cattle tick (R. microplus) adult females, brown dog tick (Rhipicephalus sanguineus) adult females and Ornithodoros moubata nymphs. These findings highlight the potential of fluralaner as a novel ectoparasiticide. Copyright © 2014 Elsevier Ltd. All rights reserved.
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            World Association for the Advancement of Veterinary Parasitology (W.A.A.V.P.) second edition: guidelines for evaluating the efficacy of parasiticides for the treatment, prevention and control of flea and tick infestations on dogs and cats.

            These second edition guidelines, updated from the 2007 version (Marchiondo et al., 2007), are intended to assist the planning and conduct of laboratory and clinical studies to assess the efficacy of ectoparasiticides applied to dogs or cats for the purpose of treating, preventing and controlling flea and tick infestations. Major revisions to this second edition include guidelines on the assessment of systemic flea and tick products, an update of the geographical distribution of the common fleas and ticks species on dogs and cats, determination of flea and tick efficacy based on geometric versus arithmetic means with respect to geographic regulatory agencies, modification of tick categorization in the assessment of efficacy, expanded guidelines on repellency and anti-feeding effects, enhanced practical field study guidance, and considerations on the ranges of flea and ticks for infestations in laboratory studies. The term ectoparasiticide includes insecticidal and acaricidal compounds, as well as insect growth regulators. The range of biological activities from animal treatment that are considered include: repellency and anti-feeding effects, knockdown, speed of kill, immediate and persistent lethal effects, and interference with egg fertility and subsequent development of off-host life cycle stages. Information is provided on the selection of animals, dose determination, dose confirmation and field studies, record keeping, interpretation of results and animal welfare. These guidelines are also intended to assist regulatory authorities involved in the approval and registration of new topical or systemic ectoparasiticides, and to facilitate the worldwide adoption of harmonized procedures.
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              Developmental Neurotoxicity of Pyrethroid Insecticides: Critical Review and Future Research Needs

              Pyrethroid insecticides have been used for more than 40 years and account for 25% of the worldwide insecticide market. Although their acute neurotoxicity to adults has been well characterized, information regarding the potential developmental neurotoxicity of this class of compounds is limited. There is a large age dependence to the acute toxicity of pyrethroids in which neonatal rats are at least an order of magnitude more sensitive than adults to two pyrethroids. There is no information on age-dependent toxicity for most pyrethroids. In the present review we examine the scientific data related to potential for age-dependent and developmental neurotoxicity of pyrethroids. As a basis for understanding this neurotoxicity, we discuss the heterogeneity and ontogeny of voltage-sensitive sodium channels, a primary neuronal target of pyrethroids. We also summarize 22 studies of the developmental neurotoxicity of pyrethroids and review the strengths and limitations of these studies. These studies examined numerous end points, with changes in motor activity and muscarinic acetylcholine receptor density the most common. Many of the developmental neurotoxicity studies suffer from inadequate study design, problematic statistical analyses, use of formulated products, and/or inadequate controls. These factors confound interpretation of results. To better understand the potential for developmental exposure to pyrethroids to cause neurotoxicity, additional, well-designed and well-executed developmental neurotoxicity studies are needed. These studies should employ state-of-the-science methods to promote a greater understanding of the mode of action of pyrethroids in the developing nervous system.
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                Author and article information

                Contributors
                kpfister@duc.ch
                robert.armstrong@merck.com
                Journal
                Parasit Vectors
                Parasit Vectors
                Parasites & Vectors
                BioMed Central (London )
                1756-3305
                8 August 2016
                8 August 2016
                2016
                : 9
                : 436
                Affiliations
                [1 ]Parasite Consulting GmbH, Wendschatzstrasse 8, CH-3006 Berne, Switzerland
                [2 ]MSD Animal Health, 2 Giralda Farms, Madison, NJ 07940 USA
                Author information
                http://orcid.org/0000-0003-2974-4161
                Article
                1719
                10.1186/s13071-016-1719-7
                4977707
                27502490
                84dfab33-07d5-49c0-b291-a67da006fe2e
                © The Author(s). 2016

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided 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 Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 2 May 2016
                : 24 July 2016
                Categories
                Review
                Custom metadata
                © The Author(s) 2016

                Parasitology
                ectoparasiticide,acaricide,insecticide,permethrin,fluralaner,dog
                Parasitology
                ectoparasiticide, acaricide, insecticide, permethrin, fluralaner, dog

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