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      Fasciola and fasciolosis in ruminants in Europe: Identifying research needs

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          Summary

          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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          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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              The Fasciola hepatica genome: gene duplication and polymorphism reveals adaptation to the host environment and the capacity for rapid evolution

              Background The liver fluke Fasciola hepatica is a major pathogen of livestock worldwide, causing huge economic losses to agriculture, as well as 2.4 million human infections annually. Results Here we provide a draft genome for F. hepatica, which we find to be among the largest known pathogen genomes at 1.3 Gb. This size cannot be explained by genome duplication or expansion of a single repeat element, and remains a paradox given the burden it may impose on egg production necessary to transmit infection. Despite the potential for inbreeding by facultative self-fertilisation, substantial levels of polymorphism were found, which highlights the evolutionary potential for rapid adaptation to changes in host availability, climate change or to drug or vaccine interventions. Non-synonymous polymorphisms were elevated in genes shared with parasitic taxa, which may be particularly relevant for the ability of the parasite to adapt to a broad range of definitive mammalian and intermediate molluscan hosts. Large-scale transcriptional changes, particularly within expanded protease and tubulin families, were found as the parasite migrated from the gut, across the peritoneum and through the liver to mature in the bile ducts. We identify novel members of anti-oxidant and detoxification pathways and defined their differential expression through infection, which may explain the stage-specific efficacy of different anthelmintic drugs. Conclusions The genome analysis described here provides new insights into the evolution of this important pathogen, its adaptation to the host environment and external selection pressures. This analysis also provides a platform for research into novel drugs and vaccines. Electronic supplementary material The online version of this article (doi:10.1186/s13059-015-0632-2) contains supplementary material, which is available to authorized users.
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                Author and article information

                Contributors
                williadj@liverpool.ac.uk
                Journal
                Transbound Emerg Dis
                Transbound Emerg Dis
                10.1111/(ISSN)1865-1682
                TBED
                Transboundary and Emerging Diseases
                John Wiley and Sons Inc. (Hoboken )
                1865-1674
                1865-1682
                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
                Affiliations
                [ 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

                Author information
                http://orcid.org/0000-0001-8186-7236
                Article
                TBED12682
                10.1111/tbed.12682
                6190748
                28984428
                dabde97b-a11f-4994-afdb-1eb36c0e7d5f
                © 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.

                History
                : 04 April 2017
                Page count
                Figures: 1, Tables: 2, Pages: 18, Words: 17740
                Funding
                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)
                Categories
                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
                2.0
                tbed12682
                May 2018
                Converter:WILEY_ML3GV2_TO_NLMPMC version:version=5.4.3 mode:remove_FC converted:16.07.2018

                Infectious disease & Microbiology
                diagnosis,fasciola hepatica,fluke,fluke vaccine,flukicide resistance,galba,helminth immunomodulation,research gaps,socio‐economics of parasite infection,transmission

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