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      Efficacy of afoxolaner in a clinical field study in dogs naturally infested with Sarcoptes scabiei Translated title: Efficacité de l’afoxolaner dans une étude de terrain clinique, chez des chiens infestés naturellement par Sarcoptes scabiei

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          Abstract

          The acaricidal efficacy of afoxolaner (NexGard ®, Merial) was evaluated against Sarcoptes scabiei var. canis in a field efficacy study, when administered orally at a minimum dose of 2.5 mg/kg to dogs naturally infested with the mites. Twenty mixed-breed dogs of either sex (6 males and 14 females), aged over 6 months and weighing 4–18 kg, were studied in this randomised controlled field efficacy trial. Dogs, naturally infested with Sarcoptes scabiei var. canis confirmed by skin scrapings collected prior to allocation, were randomly divided into two equal groups. Dogs in Group 1 were not treated. Dogs in Group 2 were treated on Days 0 and 28. On Days 0 (pre-treatment), 28 (pre-treatment) and 56, five skin scrapings of similar size were taken from different sites with lesions suggestive of sarcoptic mange. The extent of lesions was also recorded on Days 0, 28 and 56, and photographs were taken. Dogs treated orally with afoxolaner had significantly ( p < 0.001) lower mite counts than untreated control animals at Days 28 and 56 with no mites recovered from treated dogs at these times (100% efficacy based on mite counts). In addition, dogs treated with NexGard had significantly ( p < 0.05) better lesion resolution at Day 56 than Day 0; no treated dog showed pruritus compared to 7/10 dogs in the control group, 1/9 treated dogs had crusts compared to 5/10 controls and 8/9 dogs recovered 90% of hairs on lesions compared to 0/10 control dogs.

          Translated abstract

          L’efficacité acaricide de l’afoxolaner (NexGard ®, Merial), a été évaluée vis-à-vis de Sarcoptes scabiei var. canis, lors de l’administration par voie orale, à la dose minimale de 2.5 mg/kg, à des chiens naturellement infestés par les agents de gale au cours d’une étude de terrain. Vingt chiens de tout type et des deux sexes (6 mâles et 14 femelles), pesant 4 à 18 kg ont été inclus dans cette étude clinique de terrain, contrôlée et randomisée. Les chiens, confirmés comme naturellement infestés par Sarcoptes scabiei var. canis à l’aide de raclages cutanés avant leur allotement, étaient ensuite répartis de façon aléatoire dans deux groupes. Les chiens du groupe 1 n’étaient pas traités. Les chiens du groupe 2 ont été traités aux jours 0 et 28. Aux jours 0 (avant traitement), 28 (avant traitement), et 56, 5 raclages cutanés d’une même superficie ont été effectués sur 5 sites différents correspondant à des lésions de gale sarcoptique sur chaque chien. L’extension des lésions a aussi été enregistrée aux jours 0, 28, et 56, et des photographies ont été prises. Les chiens traités oralement avec l’afoxolaner ont présenté significativement ( p < 0.001) moins d’acariens que les chiens non traités aux jours 28 et 56, puisqu’aucun sarcopte n’a été retrouvé sur ces chiens lors de ces jours d’observation (soit une efficacité de 100 % sur la base des comptages d’acariens). De plus, les chiens traités au NexGard ont présenté des scores cliniques significativement inférieurs ( p < 0.05) au jour 56 par rapport à J0 ; aucun des 9 chiens traités ne présentait de prurit contre 7/10 chiens contrôles, un chien traité avait encore des croûtes contre 5/10 contrôles, et 8/9 chiens traités présentaient une repousse du poil supérieure à 90 % de la surface des lésions contre 0/10 chien contrôle.

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          Most cited references 16

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          Insecticide and acaricide molecules and/or combinations to prevent pet infestation by ectoparasites.

          External antiparasitic drugs used in cats and dogs have evolved in terms of active ingredients but also regarding formulations. Old chemical groups have been supplanted by phenylpyrazoles, neonicotinoids, oxadiazines, spinosyns or others which are entering the veterinary market. In addition to insecticides-acaricides, insect and mite growth inhibitors (IGRs) have emerged. These IGRs are used in animals or in the environment, either alone or in combination with insecticides-acaricides. The notion of antiparasitic treatment has evolved to the concept of prevention of ectoparasite infestation but also of transmitted diseases through the introduction of formulations providing long-lasting activity. At the same time, ease-of-use has been improved with the development of spot-on formulations. Progress has also been achieved through the development of antiparasitic drugs providing control of both external and internal parasites. Copyright © 2012 Elsevier Ltd. All rights reserved.
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            Discovery and mode of action of afoxolaner, a new isoxazoline parasiticide for dogs.

            Afoxolaner is an isoxazoline compound characterized by a good safety profile and extended effectiveness against fleas and ticks on dogs following a single oral administration. In vitro membrane feeding assay data and in vivo pharmacokinetic studies in dogs established an afoxolaner blood concentration of 0.1-0.2 μg/ml to be effective against both fleas (Ctenocephalides felis) and ticks (Dermacentor variabilis). Pharmacokinetic profiles in dogs following a 2.5mg/kg oral dosage demonstrated uniform and predictable afoxolaner plasma concentrations above threshold levels required for efficacy for more than one month. Dose ranging and a 5-month multi-dose experimental study in dogs, established that the 2.5mg/kg oral dosage was highly effective against fleas and ticks, and produced predictable and reproducible pharmacokinetics following repeated dosing. Mode of action studies showed that afoxolaner blocked native and expressed insect GABA-gated chloride channels with nanomolar potency. Afoxolaner has comparable potency between wild type channels and channels possessing the A302S (resistance-to-dieldrin) mutation. Lack of cyclodiene cross-resistance for afoxolaner was confirmed in comparative Drosophila toxicity studies, and it is concluded that afoxolaner blocked GABA-gated chloride channels via a site distinct from the cyclodienes. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.
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              Current trends in the treatment of Sarcoptes, Cheyletiella and Otodectes mite infestations in dogs and cats.

               Ross Curtis (2004)
              For a number of reasons, several of the more 'traditional' ectoparasiticides in the small animal veterinarian's armoury have been withdrawn over the past few years. New, safer products which are long-acting and easier to apply than the conventional dips, rinses and aerosol sprays of the past have replaced them. However, relatively few such novel acaricidal preparations have become commercially available. Consequently, practitioners and researchers frequently experiment with the drugs they have at their disposal to assess their efficacy against a variety of target acarids when used at different dosages and/or via different routes of administration, compared with those recommended by the manufacturer. This paper reviews the anecdotal and peer-reviewed reports describing the use of modern acaricides in dogs and cats that have recently appeared in the veterinary literature. It should be stressed, however, that no medicine should be prescribed for extra-label use without the informed consent of the owner.
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                Author and article information

                Journal
                Parasite
                Parasite
                parasite
                Parasite
                EDP Sciences
                1252-607X
                1776-1042
                2016
                17 June 2016
                : 23
                : ( publisher-idID: parasite/2016/01 )
                Affiliations
                [1 ] Merial S.A.S. 29 avenue Tony Garnier 69630 Lyon France
                [2 ] Clinvet International (Pty) Ltd PO Box 11186 9321 Universitas South Africa
                Author notes
                [* ]Corresponding author: frederic.beugnet@ 123456merial.com
                Article
                parasite160023 10.1051/parasite/2016026
                10.1051/parasite/2016026
                4912682
                27317462
                © F. Beugnet et al., published by EDP Sciences, 2016

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                Page count
                Figures: 0, Tables: 5, Equations: 3, References: 25, Pages: 12
                Funding
                Funded by: Merial
                Categories
                Research Article

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