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      Using Agent-Based Modelling to Predict the Role of Wild Refugia in the Evolution of Resistance of Sea Lice to Chemotherapeutants

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          Abstract

          A major challenge for Atlantic salmon farming in the northern hemisphere is infestation by the sea louse parasite Lepeophtheirus salmonis. The most frequent method of controlling these sea louse infestations is through the use of chemical treatments. However, most major salmon farming areas have observed resistance to common chemotherapeutants. In terrestrial environments, many strategies employed to manage the evolution of resistance involve the use of refugia, where a portion of the population is left untreated to maintain susceptibility. While refugia have not been deliberately used in Atlantic salmon farming, wild salmon populations that migrate close to salmon farms may act as natural refugia. In this paper we describe an agent-based model that explores the influence of different sizes of wild salmon populations on resistance evolution in sea lice on a salmon farm. Using the model, we demonstrate that wild salmon populations can act as refugia that limit the evolution of resistance in the sea louse populations. Additionally, we demonstrate that an increase in the size of the population of wild salmon results in an increased effect in slowing the evolution of resistance. We explore the effect of a population fitness cost associated with resistance, finding that in some cases it substantially reduces the speed of evolution to chemical treatments.

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          Salmon lice – impact on wild salmonids and salmon aquaculture

          Salmon lice, Lepeophtheirus salmonis, are naturally occurring parasites of salmon in sea water. Intensive salmon farming provides better conditions for parasite growth and transmission compared with natural conditions, creating problems for both the salmon farming industry and, under certain conditions, wild salmonids. Salmon lice originating from farms negatively impact wild stocks of salmonids, although the extent of the impact is a matter of debate. Estimates from Ireland and Norway indicate an odds ratio of 1.1:1-1.2:1 for sea lice treated Atlantic salmon smolt to survive sea migration compared to untreated smolts. This is considered to have a moderate population regulatory effect. The development of resistance against drugs most commonly used to treat salmon lice is a serious concern for both wild and farmed fish. Several large initiatives have been taken to encourage the development of new strategies, such as vaccines and novel drugs, for the treatment or removal of salmon lice from farmed fish. The newly sequenced salmon louse genome will be an important tool in this work. The use of cleaner fish has emerged as a robust method for controlling salmon lice, and aquaculture production of wrasse is important towards this aim. Salmon lice have large economic consequences for the salmon industry, both as direct costs for the prevention and treatment, but also indirectly through negative public opinion.
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            Fitness costs associated with insecticide resistance.

            Insects are exposed to a variety of stress factors in their environment, and, in many cases for insect pests to agriculture, those factors include toxic chemical insecticides. Coping with the toxicity of insecticides can be costly and requires energy and resource allocation for adaptation and survival. Several behavioural, physiological and genetic mechanisms are used by insects to handle toxic insecticides, sometimes leading to resistance by constitutive overexpression of detoxification enzymes or inducing mutations in the target sites. Such actions are costly and may affect reproduction, impair dispersal ability and have several other effects on the insect's fitness. Fitness costs resulting from resistance to insecticides has been reported in many insects from different orders, and several examples are given in this mini-review. Copyright © 2012 Society of Chemical Industry.
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              Drug resistance in sea lice: a threat to salmonid aquaculture.

              Sea lice are copepod ectoparasites with vast reproductive potential and affect a wide variety of fish species. The number of parasites causing morbidity is proportional to fish size. Natural low host density restricts massive parasite dispersal. However, expanded salmon farming has shifted the conditions in favor of the parasite. Salmon farms are often situated near wild salmonid migrating routes, with smolts being particularly vulnerable to sea lice infestation. In order to protect both farmed and wild salmonids passing or residing in the proximity of the farms, several measures are taken. Medicinal treatment of farmed fish has been the most predictable and efficacious, leading to extensive use of the available compounds. This has resulted in drug-resistant parasites occurring on farmed and possibly wild salmonids.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                20 October 2015
                2015
                : 10
                : 10
                : e0139128
                Affiliations
                [1 ]Centre for Veterinary and Epidemiological Research, Department of Health Management, Atlantic Veterinary College, University of Prince Edward Island, 550 University Ave, Charlottetown, PE, Canada, C1A 4P3
                [2 ]Department of Anatomy and Physiology, Atlantic Veterinary College, University of Prince Edward Island, 550 University Ave, Charlottetown, PE, Canada, C1A 4P3
                [3 ]Department of Mathematics & Statistics, University of Strathclyde, Richmond Street, Glasgow, G1 1XH, Scotland, UK
                Institute of Marine Research, NORWAY
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: GFM MLG CWR GG. Performed the experiments: GFM. Analyzed the data: GFM MLG CWR MDF GG. Wrote the paper: GFM MLG CWR MDF. Contributed to the design of the model: GFM MLG GG MDF CWR. Model Implementation: GFM MLG. Provided expert experience for parameterisation of the model: MLG MDF CWR. Design of analysis techniques: GFM CWR GG.

                Article
                PONE-D-15-16197
                10.1371/journal.pone.0139128
                4618729
                26485023
                900ea983-5e7a-4465-a423-710161721802
                Copyright @ 2015

                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
                : 14 April 2015
                : 8 September 2015
                Page count
                Figures: 8, Tables: 5, Pages: 23
                Funding
                The work received funding from both the Atlantic Innovation Fund through the Atlantic Canada Opportunities Agency (ACOA, http://www.acoa-apeca.gc.ca), and the Canada Excellence Research Chairs Program (CERC, http://upei.ca/cerc). ACOA funding is through project 199308, Tools to Resolve Environmental Impacts and Treatment Resistance in Sea Lice -2 (TREAT2). CERC funding is through project 214602. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Custom metadata
                The source code of the AnyLogic model can be downloaded from https://github.com/gmcewan/SalmonFarmRefugia.

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