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| + | Transmissible Spongiform Encephalopathies (TSEs) are neurological diseases that have been found in humans, cattle, sheep and other mammals (e.g. cats, goats, deer, antelope). The agent of disease is believed to be an abnormal prion protein (or is prion associated). An abnormal prion is a protein with an abnormal folding structure when compared to the naturally occurring prion found in nervous and lymphoreticular tissues. Various abbreviations are in use to refer to this: Prion Protein (PrP); Abnormal Prion Protein (PrP<sup>ab</sup>); Resistant Prion Protein (PrP<sup>res</sup>); Scrapie Prion Protein (PrP<sup>sc</sup>) and others. In most instances the abnormal prion is resistant to protein kinase digestion, a feature used in diagnostic techniques. Clinical signs include progressive ataxia and pruritus. Histology (immunohistochemistry) usually shows vacuolation and an accumulation of prion proteins in various parts of the CNS (especially the brain and spinal cord). |
| − | Also known as: '''''Transmissible Spongiform Encephalopathy of Sheep — TSE — Paraplexia enzootica ovium'''''
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| | + | '''Three TSEs have been recorded in small ruminants: classical scrapie, atypical scrapie and BSE.''' |
| | + | In sheep, both resistance to BSE and scrapie infection and the distribution of infectivity through the body is known to be determined genetically. Genetic resistance to TSEs is not defined in goats although research is ongoing. |
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| − | ==Introduction==
| + | '''Classical scrapie (CS)''' exists at a low prevalence in the UK sheep and goat population and thus has relatively minor animal health implications. Classical Scrapie was first recorded in 1732. There is no evidence that it is transmissible to man and some epidemiological evidence that it is not. However, it is not possible to rule out this risk completely. The Spongiform Encephalopathy Advisory Committee’s (SEAC) advice on this issue has been as follows: |
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| − | Scrapie is a '''progressive, fatal''' and '''non-febrile neurological''' disorder affecting '''sheep''' and '''goats'''. It belongs to a group of diseases called [[:Category:Transmissible Spongiform Encephalopathies|transmissible spongiform encephalopathy (TSE)]] and [[Prion Disease|other TSE’s]] include Creutzfeldt-Jakob disease in humans, [[BSE]], chronic wasting disease (CWD) in elk and deer, transmissible mink encephalopathy and feline spongiform encephalopathy has been found within cats in the UK.
| + | “…reducing the incidence of classical scrapie per se would not directly reduce the risk to public health, since classical scrapie has been evident for over 200 years and there is no evidence it poses a significant risk to human health.” [2006] |
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| − | The disease is believed to be caused by a '''conformational change in the prion (PrP)'''. A prion is a protein that occurs normally in the nervous and lymphoreticular tissues. It is only when the prion changes conformation into a protease-resistant protein PrP<sup>sc</sup> that it causes degeneration of neurological tissue. The disease causes astrocyte proliferation and then vacuolization of neurons but demyelination does not occur <ref name=" Dandoy-Dron et al., 1998 ">. Dandoy-Dron F, Guillo F, Benboudjema L, Deslys JP, Lasmézas C, Dormont D, Tovey MG, Dron M (1998) '''Gene expression in scrapie. Cloning of a new scrapie-responsive gene and the identification of increased levels of seven other mRNA transcripts.''''' Journal of Biological Chemistry,'' 273(13):7691-7697,48 ref.</ref>. The abnormal protein is thought to act as a catalyst to convert more of the host’s protein into this abnormal form.
| + | “There is no firm evidence for a link between human TSEs and classical scrapie. Although a link cannot be ruled out, even if there is a link, the human health risk from classical scrapie must be very low and result in very few human TSE cases per annum. This is because the incidence of human TSEs is very low and relatively constant world-wide (around one case per million people per year) showing that there must be at least a substantial, if not complete, barrier to transmission of classical scrapie to humans”. [2008] |
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| − | The disease has been '''notifiable in the EU''' since 1993 but unlike BSE there is no evidence to suggest that scrapie is a risk to human health <ref name="Brown et al., 1987">Brown P, Cathala F, Raubertas RF, Gajdusek DC, Castaigne P (1987) '''The epidemiology of Creutzfeldt-Jakob disease: conclusion of a 15-year investigation in France and review of the world literature. '''''Neurology, ''37(6):895-904.</ref>, <ref name="Harries et al.,1988">Harries JR, Knight R, Will RG, Cousens SN, Smith PG, Mathews WB (1988) '''Creutzfeldt-Jakob disease in England and Wales, 1980-1984: a case-control study of potential risk factors.''''' Journal of Neurology Neurosurgery and Psychiatry,'' 51(9):1113-1119.</ref>,<ref name="Kondo and Kuriowa, 1982">Kondo K, Kuriowa Y (1982)''' A case control study of Creutzfeldt-Jakob disease: association with physical injuries. '''''Annals of Neurology, 11(4):377-381.</ref>, <ref name="WHO, 1999">World Health Organization, 1999. WHO consultation on public health and animal transmissible spongiform encephalopathies: epidemiology, risk and research requirements, with the participation of the Office International des Epizooties. http://www.who.int/csr/resources/publications/bse/WHO_CDS_CSR_APH_2000,Accessed 7 March 2005. http://www.who.int/csr/resources/publications/bse/en/whocdscsraph20002.pdf.</ref>.
| + | '''Atypical scrapie (AS)''' is either not transmissible or rarely transmitted. It was first recorded in the late 90's when new testing techniques for BSE and scrapie were developed and applied. Atypical scrapie exists at a similarly low prevalence in the UK sheep and goat population as CS and has now been found in most European countries. |
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| − | Scrapie is thought to have come from imported Merino sheep from Spain and has since spread through the movement of infected sheep. Only Australia and New Zealand are recognized as being currently free of scrapie.
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| | + | BSE - a known human health risk - was confirmed in one goat slaughtered in France in 2002; and probably present in one UK goat born in 1987. Another UK goat killed in 2008 remains under investigation as BSE could not be excluded on standard tests. Naturally occurring BSE has not been recorded in sheep, and based on the results of extensive active surveillance (currently 10,000 fallen sheep, 500 fallen goats and 10,000 sheep intended for human consumption per annum). The UK’s independent Spongiform Encephalopathy Advisory Committee (SEAC) concluded in 2007, that the UK prevalence was probably 0, or at the worst 10 flocks might be affected. |
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| − | ==Pathophysiology==
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| − | Studies have suggested that after ingestion, PrP<sup>sc</sup> first accumulates in [[Peyer's Patches - Anatomy & Physiology|Peyer’s patches]] of the small intestine, [[Regional Lymphoid Tissue - Anatomy & Physiology#Structure|gut-associated lymphoid tissues (GALT)]] and ganglia of the enteric nervous system <ref name="Beekes and McBride,2000">Beekes M, McBride PA (2000) '''Early accumulation of pathological PrP in the enteric nervous system and gut-associated lymphoid tissue of hamsters orally infected with scrapie. '''''Neuroscience Letters,'' 278(3):181-184.</ref>,<ref name="Beekes et al., 1998">Beekes M, McBride PA, Baldauf E (1998) '''Cerebral targeting indicates vagal spread of infection in hamsters fed with scrapie.''''' Journal of General Virology,'' 79(3):601-607; 20 ref.</ref>, <ref name="Heggebø et al., 2000">Heggebø R, Press CM, Gunnes G, Lie KaiInge, Tranulis MA, Ulvund M, Groschup MH, Landsverk T (2000) '''Distribution of prion protein in the ileal Peyer's patch of scrapie-free lambs and lambs naturally and experimentally exposed to the scrapie agent.''''' Journal of General Virology,'' 81(9):2327-2337; 2 pp. of ref.</ref>, <ref name="Kimberlin and Walker, 1989">Kimberlin RH, Walker CA (1989) '''Pathogenesis of scrapie in mice after intragastric infection.''''' Virus Research,'' 12(3):213-220; 32 ref.</ref>, <ref name="Keulen et al., 1999">Keulen LJMvan, Schreuder BEC, Vromans MEW, Langeveld JPM, Smits MA (1999) '''Scrapie-associated prion protein in the gastro-intestinal tract of sheep with natural scrapie.''''' Journal of Comparative Pathology,'' 121(1):55-63; 24 ref.</ref>, it then spreads throughout the [[Lymph Nodes - Anatomy & Physiology|lymph nodes]], [[Tonsils - Anatomy & Physiology|tonsils]], [[Spleen - Anatomy & Physiology|spleen]], and into the [[PNS Structure - Anatomy & Physiology|peripheral nervous tissue]]. It is finally found in the brain several months later. It is extremely durable and is able to withstand high temperatures and concentrations of formaldehyde.
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| − | ==Signalment==
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| − | Scrapie affects the majority of sheep between '''3 and 5 years of age''' and has a '''long incubation period''' of two to five years. 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.
| + | [[Category:Neurological Diseases - Sheep]][[Category:Neurological Diseases - Cattle]] |
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| − | 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>.
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| − | ==Clinical Signs==
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| − | [[File:Sheep-scrapie1.jpg|thumb|200px|right|Picture from the rear shows bare patches from rubbing (Sourced from Wiki Commons)]]
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| − | 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 pruritus''' 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.
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| − | ==Diagnosis==
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| − | [[File:Scrapie lymph node immunoglobulin labeling.png|thumb|200px|right|Immunoglobulin in normal(a) and scrapie-affected (b)follicles - with light microscopy.]]
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| − | 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.
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| − | Diagnosis is confirmed on '''post-mortem''' and PrP<sup>Sc</sup> can be isolated from brainstem or lymphoid tissues by Western immunoblot, immunohistochemistry (IHC) and [[ELISA testing|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.
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| − | '''Differential diagnoses''':
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| − | :Viral encephalomyelitides ([[Suid Herpesvirus 1|pseudorabies or Aujeszky’s disease]], [[rabies]], [[Visna-Maedi Virus|maedi visna]])
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| − | :Bacterial meningoencephalomyelitides ([[listeriosis]])
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| − | :[[Pregnancy Toxaemia|Pregnancy toxemia]] (ketosis)
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| − | :Hypocalcemia-hypomagnesemia,
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| − | :Toxins (mercury, [[Lead Poisoning|lead]], organophosphates, plant toxins)
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| − | :Mange ([[Psoroptic Mange|psoroptic]], [[Sarcoptic Mange|sarcoptic]], [[Chorioptic Mange|chorioptic]]), [[:Category:Lice - Sheep|lice]], bacterial dermatitis <ref name="OIE, 2000">OIE (2000) '''Scrapie. OIE Manual of Standards for diagnostic tests and vaccines.''' 4 ed. ''Paris, France: Office International des Epizooties,'' 873-880.</ref>.
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| − | ==Treatment==
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| − | Scrapie is a fatal condition and no effective treatment is currently available
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| − | ==Control==
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| − | Good husbandry and hygiene around lambing can greatly reduce the infectious load. It is recommended that individual straw bale pens are used which can be destroyed after each lambing and that contaminated bedding and placenta should be removed immediately.
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| − | Infection can be minimised by maintaining a closed flock and only obtaining replacement ewes or breeding rams from scrapie-free flocks. Animals of resistant genotypes should be used for breeding to further minimize the risk of scrapie infection in a flock <ref name="CFIA, 2005">Canadian Food Inspection Agency (2005) '''Scrapie'''. http://www.inspection.gc.ca/english/anima/heasan/man/scrtre/scrtree.shtml, Accessed 7 March 2005.</ref>, <ref name="Dawson et al., 1998">Dawson M, Hoinville LJ, Hosie BD, Hunter N (1998) '''Guidance on the use of PrP genotyping as an aid to the control of clinical scrapie.''''' Veterinary Record,'' 142(23):623-625.</ref>, <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>, <ref name="US Department of Agriculture, 2005"> USDA (2005) '''Scrapie program.''' http://www.aphis.usda.gov/vs/nahps/scrapie/, accessed 7 March 2005.</ref>. Genetic resistance to scrapie depends on the prion genotype of the sheep and on the strain of scrapie present. Genotypes of sheep resistant to one strain of scrapie may be susceptible to another strain but on the whole the ARR allele confers resistance in all breeds. In 2001 the UK government set up the [http://animalhealth.defra.gov.uk/managing-disease/notifiable-disease/scrapie/national-scrapie-plan/ National Scrapie Plan NSP)] which aims to increase the frequency of the ARR allele within UK sheep population. Since 1988 it has been illegal for ruminant derived meat and bone meal to be fed to ruminants.
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| − | {{Learning | |
| − | |flashcards = [[Scrapie in Sheep Flashcards]]
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| − | ==References==
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| − | <references/>
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| − | {{CABI source
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| − | |datasheet = [http://www.cabi.org/ahpc/?compid=3&dsid=64847&loadmodule=datasheet&page=2144&site=160 scrapie]
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| − | |date =5 April 2011
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| − | <br><br><br>
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| − | {{review}}
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| − | {{OpenPages}}
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| − | [[Category:Neurological Diseases - Sheep]][[Category:Neurological Diseases - Goat]] | |
| | [[Category:Transmissible Spongiform Encephalopathies]] | | [[Category:Transmissible Spongiform Encephalopathies]] |
| − | [[Category:CABI Expert Review]][[Category:CABI AHPC Pages]] | + | [[Category:To_Do_-_CABI]] |
| | + | [[Category:To Do - Major]] |
Transmissible Spongiform Encephalopathies (TSEs) are neurological diseases that have been found in humans, cattle, sheep and other mammals (e.g. cats, goats, deer, antelope). The agent of disease is believed to be an abnormal prion protein (or is prion associated). An abnormal prion is a protein with an abnormal folding structure when compared to the naturally occurring prion found in nervous and lymphoreticular tissues. Various abbreviations are in use to refer to this: Prion Protein (PrP); Abnormal Prion Protein (PrPab); Resistant Prion Protein (PrPres); Scrapie Prion Protein (PrPsc) and others. In most instances the abnormal prion is resistant to protein kinase digestion, a feature used in diagnostic techniques. Clinical signs include progressive ataxia and pruritus. Histology (immunohistochemistry) usually shows vacuolation and an accumulation of prion proteins in various parts of the CNS (especially the brain and spinal cord).
Three TSEs have been recorded in small ruminants: classical scrapie, atypical scrapie and BSE.
In sheep, both resistance to BSE and scrapie infection and the distribution of infectivity through the body is known to be determined genetically. Genetic resistance to TSEs is not defined in goats although research is ongoing.
Classical scrapie (CS) exists at a low prevalence in the UK sheep and goat population and thus has relatively minor animal health implications. Classical Scrapie was first recorded in 1732. There is no evidence that it is transmissible to man and some epidemiological evidence that it is not. However, it is not possible to rule out this risk completely. The Spongiform Encephalopathy Advisory Committee’s (SEAC) advice on this issue has been as follows:
“…reducing the incidence of classical scrapie per se would not directly reduce the risk to public health, since classical scrapie has been evident for over 200 years and there is no evidence it poses a significant risk to human health.” [2006]
“There is no firm evidence for a link between human TSEs and classical scrapie. Although a link cannot be ruled out, even if there is a link, the human health risk from classical scrapie must be very low and result in very few human TSE cases per annum. This is because the incidence of human TSEs is very low and relatively constant world-wide (around one case per million people per year) showing that there must be at least a substantial, if not complete, barrier to transmission of classical scrapie to humans”. [2008]
Atypical scrapie (AS) is either not transmissible or rarely transmitted. It was first recorded in the late 90's when new testing techniques for BSE and scrapie were developed and applied. Atypical scrapie exists at a similarly low prevalence in the UK sheep and goat population as CS and has now been found in most European countries.
BSE - a known human health risk - was confirmed in one goat slaughtered in France in 2002; and probably present in one UK goat born in 1987. Another UK goat killed in 2008 remains under investigation as BSE could not be excluded on standard tests. Naturally occurring BSE has not been recorded in sheep, and based on the results of extensive active surveillance (currently 10,000 fallen sheep, 500 fallen goats and 10,000 sheep intended for human consumption per annum). The UK’s independent Spongiform Encephalopathy Advisory Committee (SEAC) concluded in 2007, that the UK prevalence was probably 0, or at the worst 10 flocks might be affected.
