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      Risk factor analysis of equine strongyle resistance to anthelmintics

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          Abstract

          Intestinal strongyles are the most problematic endoparasites of equids as a result of their wide distribution and the spread of resistant isolates throughout the world. While abundant literature can be found on the extent of anthelmintic resistance across continents, empirical knowledge about associated risk factors is missing. This study brought together results from anthelmintic efficacy testing and risk factor analysis to provide evidence-based guidelines in the field. It involved 688 horses from 39 French horse farms and riding schools to both estimate Faecal Egg Count Reduction (FECR) after anthelmintic treatment and to interview farm and riding school managers about their practices. Risk factors associated with reduced anthelmintic efficacy in equine strongyles were estimated across drugs using a marginal modelling approach. Results demonstrated ivermectin efficacy (96.3% ± 14.5% FECR), the inefficacy of fenbendazole (42.8% ± 33.4% FECR) and an intermediate profile for pyrantel (90.3% ± 19.6% FECR). Risk factor analysis provided support to advocate for FEC-based treatment regimens combined with individual anthelmintic dosage and the enforcement of tighter biosecurity around horse introduction. The combination of these measures resulted in a decreased risk of drug resistance (relative risk of 0.57, p = 0.02). Premises falling under this typology also relied more on their veterinarians suggesting practitionners play an important role in the sustainability of anthelmintic usage. Similarly, drug resistance risk was halved in premises with frequent pasture rotation and with stocking rate below five horses/ha (relative risk of 0.53, p < 0.01). This is the first empirical risk factor analysis for anthelmintic resistance in equids. Our findings should guide the implementation of more sustained strongyle management in the field.

          Highlights

          • 688 horses have been enrolled for Egg reduction rate measure.

          • Ivermectin remains efficient but fendendazole is not any more.

          • Evidence-based drenching and individual dosing lower resistance risk.

          • Higher biosecurity is associated with higher drug efficacy.

          • Premises with the least pasture constraints show higher drug efficacy.

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          Most cited references39

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          An inconvenient truth: global worming and anthelmintic resistance.

          Over the past 10-15 years, we have witnessed a rapid increase in both the prevalence and magnitude of anthelmintic resistance, and this increase appears to be a worldwide phenomenon. Reports of anthelmintic resistance to multiple drugs in individual parasite species, and in multiple parasite species across virtually all livestock hosts, are increasingly common. In addition, since the introduction of ivermectin in 1981, no novel anthelmintic classes were developed and introduced for use in livestock until recently with the launch of monepantel in New Zealand. Thus, livestock producers are often left with few options for effective treatment against many important parasite species. While new anthelmintic classes with novel mechanisms of action could potentially solve this problem, new drugs are extremely expensive to develop, and can be expected to be more expensive than older drugs. Thus, it seems clear that the "Global Worming" approach that has taken hold over the past 40-50 years must change, and livestock producers must develop a new vision for parasite control and sustainability of production. Furthermore, parasitologists must improve methods for study design and data analysis that are used for diagnosing anthelmintic resistance, especially for the fecal egg count reduction test (FECRT). Currently, standards for diagnosis of anthelmintic resistance using FECRT exist only for sheep. Lack of standards in horses and cattle and arbitrarily defined cutoffs for defining resistance, combined with inadequate analysis of the data, mean that errors in assigning resistance status are common. Similarly, the lack of standards makes it difficult to compare data among different studies. This problem needs to be addressed, because as new drugs are introduced now and in the future, the lack of alternative treatments will make early and accurate diagnosis of anthelmintic resistance increasingly important. Copyright © 2011 Elsevier B.V. All rights reserved.
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            Reduced Efficacy of Praziquantel Against Schistosoma mansoni Is Associated With Multiple Rounds of Mass Drug Administration

            The efficacy of praziquantel against Schistosoma mansoni was significantly lower in Ugandan schools that had received more prior rounds of mass drug administration, as determined by fitting a statistical model to parasite egg counts before and after treatment.
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              Pathogenicity of cyathostome infection.

              Cyathostomes are now the principle parasitic pathogen of the horse: a remarkable transformation during the last 25 years from virtual obscurity to focus of attention in equine parasitology. This rise to prominence coincides with the marked decrease in prevalence of large strongyle infections as a result of widespread use of modern anthelmintic compounds. On the basis that strongyle-associated diseases continue to commonly occur in the absence of these large strongyle species, clinical attention has turned to the pathogenicity of cyathostomes. Although many horses harbour burdens of tens of thousands of cyathostomes without developing detectable illness, these parasites can result in an inflammatory enteropathy affecting the caecum and colon. Although the principle clinical effect of cyathostomosis is weight loss, affected individuals may exhibit other signs including diarrhoea and/or subcutaneous oedema and/or pyrexia. Clinical cyathostomosis occurs more commonly in young horses in late winter/early spring but there is lifelong susceptibility to cyathostomes and they can cause clinical disease in any age of horse during any season. Animals with cyathostomosis often develop hypoalbuminaemia and/or neutrophilia but there are no clinicopathological features specific for the disease. Experimental infections with cyathostomes have resulted in both clinical and pathological features similar to those of naturally-occuring cyathostomosis cases. From the experimental infection studies, it is evident that cyathostomes are pathogenic at times of both penetration into and emergence from the large intestinal mucosa. An unusual feature of cyathostome biology is the propensity for arrested larval development within the large intestinal mucosa for more than 2 years. From limited studies it appears that this arrested larval development is favoured by: feedback from luminal to mucosal worms; larger size of challenge dose of larvae and trickle (versus single bolus) infection. During arrested larval development cyathostomes have minimal susceptibility to all anthelmintic compounds, thus, limiting the effectiveness of therapeutic and/or control strategies. Although, the relative importance of individual cyathostomes is not known, the development of species-specific DNA methods for identification of cyathostomes provides a means by which the pathogenicity of different species might be established.
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                Author and article information

                Contributors
                Journal
                Int J Parasitol Drugs Drug Resist
                Int J Parasitol Drugs Drug Resist
                International Journal for Parasitology: Drugs and Drug Resistance
                Elsevier
                2211-3207
                02 November 2017
                December 2017
                02 November 2017
                : 7
                : 3
                : 407-415
                Affiliations
                [a ]INRA/Université de Tours UMR1282 Infectiologie et Santé Publique, France
                [b ]UMR INRA/ENV Toulouse 1225 IHAP, Ecole Nationale Vétérinaire de Toulouse, France
                [c ]LUNAM University, Oniris, Unité de Recherche NP3, 102 Route de Gachet, 44300 Nantes, France
                [d ]Parasitology Dept, Dynamyc EnvA, UPEC, Ecole Nationale Vétérinaire D’Alfort, UPE, Maisons-Alfort, France
                [e ]EPIA, INRA, VetAgroSup, University of Lyon, 69280 Marcy L'Etoile, France
                [f ]Merial SAS, 29 Avenue Tony Garnier, 69007 Lyon, France
                [g ]Zoetis, 10 Rue Raymond David, 92240 Malakoff, France
                Author notes
                []Corresponding author. INRA Val de Loire, F-37380 Nouzilly, France.INRA Val de LoireNouzillyF-37380France Guillaume.Salle@ 123456inra.fr
                Article
                S2211-3207(17)30068-4
                10.1016/j.ijpddr.2017.10.007
                5727347
                29149701
                747485de-aa0f-4143-977a-d71705b4ae9d
                © 2017 The Authors

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 30 June 2017
                : 26 October 2017
                : 30 October 2017
                Categories
                Article

                horse,nematode,anthelmintic resistance,strongyle,cyathostomin

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