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A short examination protocol was used in 1002 sheep to define clinical markers suggestive of scrapie. Sheep were naturally or experimentally exposed to a classical, atypical scrapie or bovine spongiform encephalopathy agent; 312 were positive for a transmissible spongiform encephalopathy (TSE) by brain examination and included non-exposed controls. Assessed signs were posture, behaviour, menace, scratch and blindfolding response, wool loss and skin changes, body condition, incoordination and tremor. First, the combined occurrence of two or more clinical signs was compared between TSE-positive and negative sheep. Second, the importance of clinical markers was determined in a general classification and regression tree model. The main clinical markers to predict TSEs according to the tree model were incoordination and a positive scratch test. Test sensitivities and specificities were 70.8\u201381.5% and 96.1\u201393.0%, respectively, and predictive values above 87%. The results suggest that the short clinical protocol, which assesses the presence of certain clinical signs associated with a TSE in sheep and is quick to perform, may be useful to reach a suspect diagnosis in both naturally and experimentally generated TSEs.<\/jats:p>","DOI":"10.3390\/ani15091310","type":"journal-article","created":{"date-parts":[[2025,5,1]],"date-time":"2025-05-01T05:10:32Z","timestamp":1746076232000},"page":"1310","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Improving Clinical Diagnosis of Transmissible Spongiform Encephalopathies in Sheep: Which Signs Are Important?"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8361-8994","authenticated-orcid":false,"given":"Timm","family":"Konold","sequence":"first","affiliation":[{"name":"Department of Pathology & Animal Sciences, Animal & Plant Health Agency Weybridge, Addlestone KT15 3NB, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura J.","family":"Phelan","sequence":"additional","affiliation":[{"name":"Department of Pathology & Animal Sciences, Animal & Plant Health Agency Weybridge, Addlestone KT15 3NB, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1136\/vr.133.14.339","article-title":"Transmission of bovine spongiform encephalopathy to sheep and goats","volume":"133","author":"Foster","year":"1993","journal-title":"Vet. 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