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==Diagnosis==
==Diagnosis==
A pre-emptive diagnosis of scrapie may be made from the above clinical signs combined with history and confirmed with laboratory tests. As there is no immune or inflammatory response there are no serological test available for scrapie <ref name="Kasper et al., 1982"> Kasper K, Bowman K, Panitch H, Prusiner SB, 1982. Immunological studies of scrapie infection. Journal of Neuroimmunology, 3(3):187-201.</ref>, <ref name="Porter et al., 1973."> Porter D, Porter H, Cox N, 1973. Failure to demonstrate a humoral immune response to scrapie infection in mice. Journal of Immunology, 111(5):1407-1410.</ref>.
A pre-emptive diagnosis of scrapie may be made from the above clinical signs and history. As there is no immune or inflammatory response there are no serological test available for scrapie <ref name="Kasper et al., 1982"> Kasper K, Bowman K, Panitch H, Prusiner SB, 1982. Immunological studies of scrapie infection. Journal of Neuroimmunology, 3(3):187-201.</ref>, <ref name="Porter et al., 1973."> Porter D, Porter H, Cox N, 1973. Failure to demonstrate a humoral immune response to scrapie infection in mice. Journal of Immunology, 111(5):1407-1410.</ref>.
Pathologic lesions are confined to the CNS. Histology (immunohistochemistry) usually shows vacuolation and an accumulation of prion proteins in various parts of the CNS (medulla, pons, midbrain, and spinal cord. However vacuolation is not completely diagnostic since it may also be present to a lesser extent in the brains of healthy sheep <ref name="Fraser, 1976"> Fraser H, 1976. The pathology of a natural and experimental scrapie. Frontiers of Biology, 44:267-305.</ref>, <ref name="Zlotnik and Rennie, 1958"> Zlotnik I, Rennie JC, 1958. A comparative study of the incidence of vacuolated neurones in the medulla from apparently healthy sheep of various breeds. Journal of Comparative Pathology, 68:411-415.</ref>. In most instances the abnormal prion is resistant to protein kinase digestion, a feature used in diagnostic techniques.
Hypocalcemis-hypomagnesemia, Toxins (mercury, lead, organophosphates, plant toxins) and Mange, lice, bacterial dermatitis <ref name="OIE, 2000" />, <ref name="Radostits et al., 2000"> </ref>.
PrP<sup>Sc</sup> from post-mortem brainstem or lymphoid tissues may be detected by Western immunoblot analysis <ref name="Farquhar et al., 1989">Farquhar CF, Somerville RA, Ritchie LA, 1989. Post-mortem immunodiagnosis of scrapie and bovine spongiform encephalopathy. Journal of Virological Methods, 24(1, 2):215-222; 21 ref.</ref>, <ref name="Stack et al., 1996"> Stack MJ, Keyes P, Scott AC, 1996. The diagnosis of bovine spongiform encephalopathy and scrapie by the detection of fibrils and the abnormal protein isoform. In: Baker H, Ridley RM, eds. Methods in molecular medicine: prion diseases. Totowa, New Jersey, USA: Humana Press, 85-103.</ref>, <ref name="Wadsworth et al., 2001 "> Wadsworth JDF, Joiner S, Hill AF, Campbell TA, Desbruslais M, Luthert PJ, Collinge J, 2001. Tissue distribution of protease resistant prion protein in variant Creutzfeldt-Jakob disease using a highly sensitive immunoblotting assay. Lancet, 358(9277):171-180.</ref> and immunohistochemistry (IHC) <ref name="Miller et al., 1993">Miller JM, Jenny AL, Taylor WD, Marsh RF, Rubenstein R, Race RE, 1993. Immunohistochemical detection of prion protein in sheep with scrapie. Journal of Veterinary Diagnostic Investigation, 5(3):309-316; 38 ref.</ref>, <ref name="Miller et al., 1994">Miller JM, Jenny AL, Taylor WD, Race RE, Ernst DR, Katz JB, Rubenstein R, 1994. Detection of prion protein in formalin-fixed brain by hydrated autoclaving immunohistochemistry for the diagnosis of scrapie in sheep. Journal of Veterinary Diagnostic Investigation, 6(3):366-368; 10 ref</ref>, <ref name="O'Rourke et al., 1998">O'Rourke KI, Baszler TV, Parish SM, Knowles DP, 1998. Preclinical detection of PrP in nictitating membrane lymphoid tissue of sheep. Veterinary Record, 142(18):489-491; 14 ref.</ref>, <ref name="Keulen et al., 1996; ">Keulen LJMvan, Schreuder BEC, Meloen RH, Mooij-Harkes G, Vromans MEW, Langeveld JPM, 1996. Immunohistochemical detection of prion protein in lymphoid tissues of sheep with natural scrapie. Journal of Clinical Microbiology, 34(5):1228-1231; 26 ref.</ref>, <ref name="Keulen et al., 1995">Keulen LJMvan, Schreuder BEC, Meloen RH, Berg MPvan den, Mooij-Harkes G, Vromans MEW, Langeveld JPM, 1995. Immunohistochemical detection and localization of prion protein in brain tissue of sheep with natural scrapie. Veterinary Pathology, 32(3):299-308; 35 ref.</ref>. Transmission to mice by injecting suspect tissue can be used to assay infectivity <ref name="OIE, 2000 " />. Tonsil <ref name="Schreuder et al., 1998">Schreuder BEC, Keulen LJMvan, Vromans MEW, Langeveld JPM, Smits MA, 1998. Tonsillar biopsy and PrP detection in the preclinical diagnosis of scrapie. Veterinary Record, 142(21):564-568; 31 ref. </ref>, <ref name="Schreuder et al., 1996 ">Schreuder BEC, Keulen LJMvan, Vromans MEW, Langeveld JPM, Smits MA, 1996. Preclinical test for prion diseases. Nature (London), 381(6583):563; 10 ref.</ref> and lymphoid biopsies <ref name=" Bender et al., 2004"> Bender S, Alverson J, Herrmann LM, O’Rourke KI, 2004. Histamine as an aid to biopsy of third eyelid lymphoid tissue in sheep. Veterinary Record, 154(21):662-663.</ref>, <ref name="Ikegami et al., 1991">Ikegami Y, Ito M, Isomura H, Momotani E, Sasaki K, Muramatsu Y, Ishiguro N, Shinagawa M, 1991. Pre-clinical and clinical diagnosis of scrapie by detection of PrP protein in tissues of sheep. Veterinary Record, 128(12):271-275; 16 ref.</ref>, <ref name="O'Rourke et al., 2000">O'Rourke KI, Baszler TV, Besser TE, Miller JM, Cutlip RC, Wells GAH, Ryder SJ, Parish SM, Hamir AN, Cockett NE, Jenny A, Knowles DP, 2000. Preclinical diagnosis of scrapie by immunohistochemistry of third eyelid lymphoid tissue. Journal of Clinical Microbiology, 38(9):3254-3259; 33 ref.</ref>, <ref name="O'Rourke et al., 1998">O'Rourke KI, Baszler TV, Miller JM, Spraker TR, Sadler-Riggleman I, Knowles DP, 1998. Monoclonal antibody F89/160.1.5 defines a conserved epitope on the ruminant prion protein. Journal of Clinical Microbiology, 36(6):1750-1755; 41 ref.</ref>, <ref name="Thuring et al., 2000 ">Thuring CMA, Sweeney T, McElroy MC, Weavers E, 2000. Suitability of protuberances on the third eyelids of sheep as a biopsy site for lymphoid follicles. Veterinary Record, 147(22):631-632; 10 ref.</ref> stained for PrP<sup>sc</sup> by using IHC have been used for preclinical scrapie screening.
Rapid tests for surveillance that have been approved by the EU include: Western blot test for the detection of the protease-resistant fragment PrP<sup>Res</sup>(Prionics Check test),
Chemiluminescent ELISA test involving an extraction method and an ELISA technique, using an enhanced chemiluminescent reagent(Enfer test)and sandwich immunoassay for PrP<sup>Res</sup> carried out following denaturation and concentration steps (Bio-Rad test)<ref name="European Commission, 2001">European Commission, 2001. Commission Regulation (EC) No. 999/2001 of the European Parliament and of the Council of 22 May 2001 laying down rules for the prevention, control and eradication of certain transmissible spongiform encephalopathies. Official Journal of the European Communities, L 147:1-40.</ref>.
'''Differential diagnosis''': Viral encephalomyelitides (pseudorabies or Aujeszky’s disease, rabies, maedi visna), Bacterial meningoencephalomyelitides (listeriosis), Pregnancy toxemia (ketosis), Hypocalcemis-hypomagnesemia, Toxins (mercury, lead, organophosphates, plant toxins) and Mange, lice, bacterial dermatitis <ref name="OIE, 2000" />.
==Treatment==
==Treatment==