Changes

==Signalment==  

==Signalment==  

Scrapie affects the majority of sheep between 3 and 5 years of age and has a long incubation period of two to five years.  It is extremely durable and is able to withstand high temepratures and concentrations of formaldehyde.  Unlike BSE, scrapie is influenced by breed and genetic variation of the PrP gene within sheep populations, which can affect the infectivity and incubation period of the scrapie.  The disease has been shown to be effectively transmitted during lambing <ref name="Dickinson et al., 1974"> Dickinson AG, Stamp JT, Renwick CC, 1974. Maternal and lateral transmission of scrapie in sheep. Journal of Comparative Pathology, 84(1):19-25.</ref>, <ref name="Hourrigan et al., 1979">Hourrigan JL, Klingsporn AI, Clark WW, DeCamp M, 1979. Epidemiology of scrapie in the US. In: Prusiner SB, Hadlow W, eds. Slow transmissible diseases of the nervous system. New York: Academic Press, 331-356.</ref>, and experimental studies have shown that the ingestion of infected placenta can spread the disease in sheep and goats <ref name="Pattison et al., 1972">Pattison IH, Hoare MN, Jebbett JN, 1972. Spread of scrapie to sheep and goats by oral dosing with foetal membranes from scrapie-affected sheep. Veterinary Record, 90(17):465-468.</ref>.

Scrapie affects the majority of sheep between 3 and 5 years of age and has a long incubation period of two to five years.  It is extremely durable and is able to withstand high temperatures and concentrations of formaldehyde.  Unlike BSE, scrapie is influenced by breed and genetic variation of the PrP gene within sheep populations, which can affect the infectivity and incubation period of the scrapie.  The disease has been shown to be effectively transmitted during lambing <ref name="Dickinson et al., 1974"> Dickinson AG, Stamp JT, Renwick CC, 1974. Maternal and lateral transmission of scrapie in sheep. Journal of Comparative Pathology, 84(1):19-25.</ref>, <ref name="Hourrigan et al., 1979">Hourrigan JL, Klingsporn AI, Clark WW, DeCamp M, 1979. Epidemiology of scrapie in the US. In: Prusiner SB, Hadlow W, eds. Slow transmissible diseases of the nervous system. New York: Academic Press, 331-356.</ref>, and experimental studies have shown that the ingestion of infected placenta can spread the disease in sheep and goats <ref name="Pattison et al., 1972">Pattison IH, Hoare MN, Jebbett JN, 1972. Spread of scrapie to sheep and goats by oral dosing with foetal membranes from scrapie-affected sheep. Veterinary Record, 90(17):465-468.</ref>.

==Clinical Signs==

==Clinical Signs==

[[File:Sheep-scrapie1.jpg|thumb|200px|left|Picture from the rear shows bare patches from rubbing (Sourced from Wiki Commons)]]

[[File:Sheep-scrapie1.jpg|thumb|200px|left|Picture from the rear shows bare patches from rubbing (Sourced from Wiki Commons)]]

Early clinical signs may include subtle '''behavioural and neuorological changes'''.  Sheep often have a fixed gaze, and suffer from bruxism, fine tremors, and hyperaesthesia to sound or sudden movements. Affected animals may later become exercise intolerant and develop '''progressive ataxia'''.  Sheep often find difficulty in turning, sway on their hind hindquarters and have gait abnormalities such as a high stepping gait in the forelimbs or a bunny hopping gait in the hindlimbs. Some sheep have '''intense pruritis''' that leads to compulsive rubbing, nibbling at the skin, or scraping against fixed objects.  Wool loss is typically seen over the hindquarters and lateral thorax. Lip smacking or '''nibbling reflex''' can often be elicited by scratching over the lumbar region, which is characteristic og scrapie. Significant weight loss with or without a decrease in appetite, weakness, recumbency, and death are all seen within the later stages of the disease.  

Early clinical signs may include subtle '''behavioural and neurological changes'''.  Sheep often have a fixed gaze, and suffer from bruxism, fine tremors, and hyperaesthesia to sound or sudden movements. Affected animals may later become exercise intolerant and develop '''progressive ataxia'''.  Sheep often find difficulty in turning, sway on their hind hindquarters and have gait abnormalities such as a high stepping gait in the forelimbs or a bunny hopping gait in the hind limbs. Some sheep have '''intense pruritis''' that leads to compulsive rubbing, nibbling at the skin, or scraping against fixed objects.  Wool loss is typically seen over the hindquarters and lateral thorax. Lip smacking or '''nibbling reflex''' can often be elicited by scratching over the lumbar region, which is characteristic of scrapie. Significant weight loss with or without a decrease in appetite, weakness, recumbency, and death are all seen within the later stages of the disease.  

==Diagnosis==

==Diagnosis==

[[File:800px-Scrapie lymph node immunoglobulin labeling.png|thumb|200px|left|Immunoglobulin in normal(a) and scrapie-affected (b)follicles -with light microscopy.]]A pre-emptive diagnosis of scrapie may be made from the above clinical signs and history. There are no serological test available for scrapie, as is does not evoke an immune or inflammatory response.  Diagnosis is confirmed on postmortem and PrP^Sc can be isolated from brainstem or lymphoid tissues by Western immunoblot, immunohistochemistry (IHC) and elisa tests.  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. IHC staining of tonsil and lymphoid biopsies have been used for preclinical scrapie testing and the third eyelid lymphoid tissue can be used for diagnosis in sheep.  

[[File:800px-Scrapie lymph node immunoglobulin labeling.png|thumb|200px|left|Immunoglobulin in normal(a) and scrapie-affected (b)follicles -with light microscopy.]]A pre-emptive diagnosis of scrapie may be made from the above clinical signs and history. There are no serological test available for scrapie, as is does not evoke an immune or inflammatory response.  Diagnosis is confirmed on post-mortem and PrP^Sc can be isolated from brainstem or lymphoid tissues by Western immunoblot, immunohistochemistry (IHC) and Elisa tests.  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. IHC staining of tonsil and lymphoid biopsies have been used for preclinical scrapie testing and the third eyelid lymphoid tissue can be used for diagnosis in sheep.