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      Development of superficial lung lesions monitored on farm by serial ultrasonographic examination in sheep with lesions confirmed as ovine pulmonary adenocarcinoma at necropsy

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          Abstract

          Background

          This ultrasonographic study monitored lesions involving the lung surface suspected to be the early stages of ovine pulmonary adenocarcinoma (OPA) tumours over 4 months in commercially farmed sheep. The enlargement of these lesions defined ultrasonographically, which likely represent the development of OPA tumours, have important implications for ultrasound screening schedules in veterinary management plans attempting to eliminate OPA by test-and-cull.

          Results

          The lungs of 58 adult Scottish Blackface sheep with ultrasonographic changes at the lung surface consistent with early OPA tumours were examined two to six times over 40 to 290 days. Lesion development, represented in early video recordings by 2–3 mm lesions involving the visceral pleural and comet tails, then a decreasing length of the hyperechoic line representing the normal visceral pleura and increasing depth of the sharply-demarcated and largely uniform hypoechoic areas into the lung parenchyma, was found in 26 of the 58 sheep. The rate at which the sonographic lesions progressed varied considerably and in 10 of 17 Group 1 sheep developed quickly from an estimated depth of 2–30 mm up to 70 mm between 60 and 120 days later. These sonographic lesions were confirmed as OPA at necropsy; histological changes of concurrent bacterial infection were detected in one of these 10 Group 1 sheep. Thirty-one sheep had sonographic changes ≤30 mm consistent with very early OPA at the first examination which had reduced or were not observed at subsequent examination. Five of these 31 sheep were necropsied, 3 had small OPA lesions while 2 had no significant pathology.

          Conclusion

          Lesions involving the visceral pleura, with sonographic changes consistent with previous published findings of early OPA, developed over 40–120 days to large masses in 10 of 17 Group 1 sheep with the provisional sonographic diagnosis confirmed histologically at necropsy. While it is possible that atalectic lung could have caused some of the minor sonographic changes there was no microscopic evidence of pathologies other than OPA in nine of 10 Group 1 sheep. We conclude that some small tumours progress to large tumours within 3 months questioning the assumption that OPA is a slow growing tumour in adult sheep taking several years to cause clinical disease. The findings that a proportion of small ultrasonographic lesions are not found again at subsequent scanning illustrates the challenges of interpreting small (< 1–2 cm) lesions during rapid whole flock ultrasonographic examination and we continue to recommend re-scanning suspicious sonographic changes 2 months later.

          Electronic supplementary material

          The online version of this article (10.1186/s13620-018-0134-0) contains supplementary material, which is available to authorized users.

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          Most cited references25

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          Pathology and pathogenesis of ovine pulmonary adenocarcinoma.

          Ovine pulmonary adenocarcinoma (OPA), also known as jaagsiekte, is a transmissible lung tumour of sheep caused by jaagsiekte sheep retrovirus (JSRV). JSRV induces neoplastic transformation of alveolar and bronchiolar secretory epithelial cells and the resulting tumours can grow to occupy a significant portion of the lung. Tumour growth is frequently accompanied by the overproduction of fluid in the lung, which further compromises normal respiration. The period between infection and the appearance of clinical signs may be several months or years and many JSRV-infected sheep do not exhibit clinical signs at all during their lifespan. This allows the spread of OPA into new flocks through contact with infected but apparently normal animals. OPA was first described in the early 19th century; however, it has still not been possible to devise effective methods for controlling its spread and it remains an important problem in most countries where sheep are farmed. This is due in part to the absence of an immunological response to JSRV in infected animals, which has hindered the development of serological diagnostic tests and vaccines. In addition to its veterinary importance, OPA is regarded as a potential large animal model for human lung adenocarcinoma and this has stimulated research into the pathogenesis of the ovine disease. This work has produced some significant results, including the finding that one of the JSRV structural proteins is directly involved in oncogenesis. The recent advances in understanding JSRV and the pathogenesis of OPA should lead to novel strategies for diagnosis and control of this disease and for its exploitation as a comparative model for human lung cancer. Copyright 2010 Elsevier Ltd. All rights reserved.
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            Jaagsiekte sheep retrovirus is present at high concentration in lung fluid produced by ovine pulmonary adenocarcinoma-affected sheep and can survive for several weeks at ambient temperatures.

            Jaagsiekte sheep retrovirus (JSRV) causes a fatal lung cancer of sheep known as ovine pulmonary adenocarcinoma (OPA). OPA is a significant disease in many sheep-rearing countries and there is no effective method of control. A unique feature of OPA is the overproduction of fluid in the lung of affected animals. This lung fluid contains JSRV and provides a means of transmission through the inhalation of virus. In this study we demonstrated that lung fluid from different OPA cases contained between 10(7) and 10(10) copies of JSRV RNA per ml. Examination of JSRV RNA survival under conditions that mimic natural conditions suggested that intact JSRV virions may persist for several weeks in the environment. These are the first quantitative data on JSRV in lung fluid and provide valuable information for implementing appropriate biosecurity measures to control the spread of JSRV in the field.
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              Infection of lung epithelial cells and induction of pulmonary adenocarcinoma is not the most common outcome of naturally occurring JSRV infection during the commercial lifespan of sheep.

              Jaagsiekte sheep retrovirus (JSRV) is the causative agent of ovine pulmonary adenocarcinoma (OPA). In this study, we followed over a 31-month period the natural transmission of JSRV in adult sheep and in their offspring. We established groups derived from flocks with either a high or low incidence of OPA and monitored virus transmission, clinical disease and macroscopic/microscopic lung lesions at necropsy. Results obtained show that (i) JSRV infection can occur perinatally or in the first few months of life in lambs and in adult sheep; (ii) only a minority of JSRV-infected animals develop clinical disease during their commercial lifespan; and (iii) JSRV is more readily detectable in peripheral blood leucocytes and lymphoid organs than in the lungs. These data support a model of opportunistic JSRV infection and tumorigenic conversion of type II pneumocytes/Clara cells in the lungs, while lymphoreticular cells serve as the principal virus reservoir.
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                Author and article information

                Contributors
                PhilScottfrcvs@gmail.com
                mark.dagleish@moredun.ac.uk
                chris.cousens@moredun.ac.uk
                Journal
                Ir Vet J
                Ir Vet J
                Irish Veterinary Journal
                BioMed Central (London )
                0368-0762
                2046-0481
                5 November 2018
                5 November 2018
                2018
                : 71
                : 23
                Affiliations
                [1 ]Capital Veterinary Services, West Latchfields, Scotland, EH41 4JN UK
                [2 ]ISNI 0000 0001 2186 0964, GRID grid.420013.4, Moredun Research Institute, ; Bush Loan, Scotland, Penicuik EH26 0PZ UK
                Article
                134
                10.1186/s13620-018-0134-0
                6219085
                30450192
                c09e971f-6bc8-41d9-9adb-bc5485eb5bea
                © The Author(s). 2018

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 24 August 2018
                : 18 October 2018
                Funding
                Funded by: RESAS
                Funded by: Clyde Wind Farm Community and Development Fund
                Categories
                Research
                Custom metadata
                © The Author(s) 2018

                Veterinary medicine
                ovine pulmonary adenocarcinoma,opa,jaagsiekte,ultrasonography,disease control
                Veterinary medicine
                ovine pulmonary adenocarcinoma, opa, jaagsiekte, ultrasonography, disease control

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