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      Fasciola and fasciolosis in ruminants in Europe: Identifying research needs


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          Fasciola hepatica is a trematode parasite with a global distribution, which is responsible for considerable disease and production losses in a range of food producing species. It is also identified by WHO as a re‐emerging neglected tropical disease associated with endemic and epidemic outbreaks of disease in human populations. In Europe, F. hepatica is mostly associated with disease in sheep, cattle and goats. This study reviews the most recent advances in our understanding of the transmission, diagnosis, epidemiology and the economic impact of fasciolosis. We also focus on the impact of the spread of resistance to anthelmintics used to control F. hepatica and consider how vaccines might be developed and applied in the context of the immune‐modulation driven by the parasite. Several major research gaps are identified which, when addressed, will contribute to providing focussed and where possible, bespoke, advice for farmers on how to integrate stock management and diagnosis with vaccination and/or targeted treatment to more effectively control the parasite in the face of increasing the prevalence of infection and spread of anthelmintic resistance that are likely to be exacerbated by climate change.

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          Most cited references 191

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          Identification of an interleukin (IL)-25–dependent cell population that provides IL-4, IL-5, and IL-13 at the onset of helminth expulsion

          Type 2 immunity, which involves coordinated regulation of innate and adaptive immune responses, can protect against helminth parasite infection, but may lead to allergy and asthma after inappropriate activation. We demonstrate that il25−/− mice display inefficient Nippostrongylus brasiliensis expulsion and delayed cytokine production by T helper 2 cells. We further establish a key role for interleukin (IL)-25 in regulating a novel population of IL-4–, IL-5–, IL-13–producing non–B/non–T (NBNT), c-kit+, FcɛR1− cells during helminth infection. A deficit in this population in il25−/− mice correlates with inefficient N. brasiliensis expulsion. In contrast, administration of recombinant IL-25 in vivo induces the appearance of NBNT, c-kit+, FcɛR1− cells and leads to rapid worm expulsion that is T and B cell independent, but type 2 cytokine dependent. We demonstrate that these IL-25–regulated cells appear rapidly in the draining lymph nodes, implicating them as a source of type 2 cytokines during initiation of worm expulsion.
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            FLOTAC: new multivalent techniques for qualitative and quantitative copromicroscopic diagnosis of parasites in animals and humans.

            Accurate diagnosis of parasitic infections is of pivotal importance for both individual patient management and population-based studies, such as drug efficacy trials and surveillance of parasitic disease control and elimination programs, in both human and veterinary public health. In this study, we present protocols for the FLOTAC basic, dual and double techniques, which are promising new multivalent, sensitive, accurate and precise methods for qualitative and quantitative copromicroscopic analysis. These various methods make use of the FLOTAC apparatus, a cylindrical device with two 5-ml flotation chambers, which allows up to 1 g of stool to be prepared for microscopic analysis. Compared with currently more widely used diagnostic methods for parasite detection in animals (e.g., McMaster and Wisconsin techniques) and humans (e.g., Kato-Katz and ether-based concentration techniques), the FLOTAC techniques show higher sensitivity and accuracy. All FLOTAC techniques can be performed on fresh fecal material as well as preserved stool samples, and require approximately 12-15 min of preparation time before microscopic analysis.
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              IL-33, a potent inducer of adaptive immunity to intestinal nematodes.

              IL-33 (IL-1F11) binds ST2 (IL-1R4), both of which are associated with optimal CD4(+) Th2 polarization. Exogenous IL-33 drives induction of Th2-associated cytokines and associated pathological changes within the gut mucosa. Th2 polarization is also a prerequisite to expulsion of the intestinal-dwelling nematode Trichuris muris. In this study, we demonstrate that IL-33 mRNA is expressed early during parasite infection and susceptible mice can be induced to expel the parasite by a regime of exogenous IL-33 administration. IL-33 prevents an inappropriate parasite-specific Th1-polarized response and induces IL-4, IL-9, and IL-13. This redirection requires the presence of T cells and must occur at the initiation of the response to the pathogen. Interestingly, exogenous IL-33 also induced thymic stromal lymphopoietin mRNA within the infected caecum, an epithelial cell-restricted cytokine essential for the generation of Th2-driven parasite immunity. IL-33 also acts independently of T cells, altering intestinal pathology in chronically infected SCID mice, leading to an increased crypt length and intestinal epithelial cell proliferation, but reducing goblet cell hyperplasia. Thus, the ability of IL-33 to induce Th2 responses has functional relevance in the context of intestinal helminth infection, particularly during the initiation of the response.

                Author and article information

                Transbound Emerg Dis
                Transbound Emerg Dis
                Transboundary and Emerging Diseases
                John Wiley and Sons Inc. (Hoboken )
                06 October 2017
                May 2018
                : 65
                : Suppl Suppl 1 , DISCONTOOLS Supplement: Current research gaps for advancing control of infectious diseases in production animals ( doiID: 10.1111/tbed.2018.65.issue-S1 )
                : 199-216
                [ 1 ] Institute of Infection and Global Health University of Liverpool Liverpool UK
                [ 2 ] Health Protection Research Unit in Emerging and Zoonotic Infections University of Liverpool Liverpool UK
                [ 3 ] Avia‐GIS Zoersel Belgium
                [ 4 ] Universidad de Cordoba Cordoba Spain
                [ 5 ] Instituto de Ganaderia de Montana CSIC Universidad de Leon Grulleros Leon Spain
                [ 6 ] Department of Veterinary Medicine and Animal Productions University of Naples Federico II Napoli Italy
                Author notes
                [* ] Correspondence

                D. J. L. Williams, Institute of Infection and Global Health, University of Liverpool, Liverpool, UK.

                Email: williadj@ 123456liverpool.ac.uk

                © 2017 The Authors. Transboundary and Emerging Diseases Published by Blackwell Verlag GmbH

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                Page count
                Figures: 1, Tables: 2, Pages: 18, Words: 17740
                Funded by: European Union
                Funded by: Biotechnology and Biological Sciences Research Council (BBSRC)
                Funded by: Spanish “Ramón y Cajal” Programme of the Ministry of Economy and Competitiveness
                Award ID: RYC‐2015‐18368
                Funded by: National Institute for Health Research Health Protection Research Unit (NIHR HPRU)
                Discontools Supplement
                DISCONTOOLS Supplement: Current research gaps for advancing control of infectious diseases in production animals. Guest Editors: J. Charlier and H.W. Barkema
                Discontools Supplement
                Custom metadata
                May 2018
                Converter:WILEY_ML3GV2_TO_NLMPMC version:version=5.4.3 mode:remove_FC converted:16.07.2018


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