Difference between revisions of "Scrapie"

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==Introduction==  
 
==Introduction==  
Scrapie was first described in the UK in 1732 <ref name=" McGowan, 1922 "> McGowan JP, 1922. Scrapie in sheep. Scottish Journal of Agriculture, 5:365-375.</ref>, <ref name=" Pattison, 1988 "> Pattison IH, 1988. Fifty years with scrapie: a personal reminiscence. Veterinary Record, 123(26-27):661-666; 60 ref.</ref>,  and recognised as an infectious disease in 1936 <ref name="Chelle, 1942"> Chelle PL, 1942. Un cas de tremblante chez la chèvre. Bulletin Académie Vétérinaire de France, 15:294-295.</ref>, <ref name="Poser, 2002">Poser CM, 2002. Notes on the history of the prion diseases. Part I. Clinical Neurology and Neurosurgery, 104(1):1-9.</ref>.  It is a progressive, fatal and non-febrile neurological disorder affecting sheep and goats.  It belongs to a group of diseases called transmissible spongiform encephalopathy (TSE) and 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. 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.  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>. Studies on the spread of scrapie infectivity have suggested that after oral intake, PrPSc first accumulates in Peyer’s patches of the small intestine, 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>.  PrPSc then moves onward to the tonsil, spleen, retropharyngeal lymph nodes, mesenteric lymph nodes, and peripheral nervous tissue <ref name=" Mabbott and Bruce, 2001 ">Mabbott NA, Bruce ME, 2001. The immunobiology of TSE diseases. Journal of General Virology, 82(10):2307-2318; many ref.</ref>, <ref name="Maignien et al., 1999 ">Maignien T, Lasmézas CI, Beringue V, Dormont D, Deslys JP, 1999. Pathogenesis of the oral route of infection of mice with scrapie and bovine spongiform encephalopathy agents. Journal of General Virology, 80(11):3035-3042; 32 ref.</ref>,<ref name="Press et al., 2004"> Press CM, Heggebø R, Espenes A, 2004. Involvement of gut-associated lymphoid tissue of ruminants in the spread of transmissible spongiform encephalopathies. Advanced Drug Delivery Reviews, 56(6):885-899.</ref>. PrPSc eventually spreads to most lymph nodes and the central nervous system (CNS). PrPSc can be found in the lymphoreticular system tissues for months before it is found in the brain <ref name="Eklund et al., 1967">Eklund CM, Kennedy RC, Hadlow WJ, 1967. Pathogenesis of scrapie virus infection in the mouse. Journal of Infectious Diseases, 117(1):15-22.</ref>; <ref name="Hadlow et al., 1974"> Hadlow W, Eklund CM, Kennedy RC, Jackson TA, Whitford HW, Boyle CC, 1974. Course of experimental scrapie virus infection in the goat. Journal of Infectious Diseases, 129(5):559-567.</ref>; <ref name="Hadlow et al., 1982"> Hadlow W, Kennedy RC, Race RE, 1982. Natural infection of Suffolk sheep with scrapie virus. Journal of Infectious Diseases, 146(5):657-664.</ref>; <ref name="Hadlow et al., 1980"> Hadlow WJ, Kennedy RC, Race RE, Eklund CM, 1980. Virologic and neurohistologic findings in dairy goats affected with natural scrapie. Veterinary Pathology, 17(2):187-199.</ref>; <ref name="Hadlow et al., 1979"> Hadlow WJ, Race RE, Kennedy RC, Eklund CM, 1979. Natural infection of sheep with scrapie virus. Slow transmissible diseases of the nervous system. Volume 2., 3-12; 5 ref.</ref>. Affected animals may live one to six months after onset of clinical signs <ref name="Capucchio et al., 2001">Capucchio MT, Guarda F, Pozzato N, Coppolino S, Caracappa S, Marco Vdi, 2001. Clinical signs and diagnosis of scrapie in Italy: a comparative study in sheep and goats. Journal of Veterinary Medicine. Series A, 48(1):23-31; 11 ref.</ref>; <ref name="Foster et al., 2001a "> Foster J, Goldmann W, Parnham D, Chong A, Hunter N, 2001a. Partial dissociation of PrP deposition and vacuolation in the brains of scrapie and BSE experimentally affected goats. Journal of General Virology, 82(1):267-273; 30 ref.</ref> , <ref name="Foster et al., 2001b ">Foster JD et al., 2001b. Clinical signs, histopathology and genetics of experimental transmission of BSE and natural scrapie to sheep and goats. Vet. Rec., 148:165-171.</ref>,<ref name="Foster et al., 2001c "> Foster JD, Parnham D, Chong A, Goldmann W, Hunter N, 2001c. Clinical signs, histopathology and genetics of experimental transmission of BSE and natural scrapie to sheep and goats. Veterinary Record, 148(6):165-171; 22 .</ref>, <ref name="USDA, 2005."> USDA, 2005. Scrapie program. http://www.aphis.usda.gov/vs/nahps/scrapie/, accessed 7 March 2005. </ref>
+
Scrapie was first described in the UK in 1732 <ref name=" McGowan, 1922 "> McGowan JP, 1922. Scrapie in sheep. Scottish Journal of Agriculture, 5:365-375.</ref>, <ref name=" Pattison, 1988 "> Pattison IH, 1988. Fifty years with scrapie: a personal reminiscence. Veterinary Record, 123(26-27):661-666; 60 ref.</ref>,  and recognised as an infectious disease in 1936 <ref name="Chelle, 1942"> Chelle PL, 1942. Un cas de tremblante chez la chèvre. Bulletin Académie Vétérinaire de France, 15:294-295.</ref>, <ref name="Poser, 2002">Poser CM, 2002. Notes on the history of the prion diseases. Part I. Clinical Neurology and Neurosurgery, 104(1):1-9.</ref>.  It is a progressive, fatal and non-febrile neurological disorder affecting sheep and goats.  It belongs to a group of diseases called transmissible spongiform encephalopathy (TSE) and 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. 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.  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>. Studies on the spread of scrapie infectivity have suggested that after oral intake, PrPSc first accumulates in Peyer’s patches of the small intestine, 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>.  PrPSc then moves onward to the tonsil, spleen, retropharyngeal lymph nodes, mesenteric lymph nodes, and peripheral nervous tissue <ref name=" Mabbott and Bruce, 2001 ">Mabbott NA, Bruce ME, 2001. The immunobiology of TSE diseases. Journal of General Virology, 82(10):2307-2318; many ref.</ref>, <ref name="Maignien et al., 1999 ">Maignien T, Lasmézas CI, Beringue V, Dormont D, Deslys JP, 1999. Pathogenesis of the oral route of infection of mice with scrapie and bovine spongiform encephalopathy agents. Journal of General Virology, 80(11):3035-3042; 32 ref.</ref>,<ref name="Press et al., 2004"> Press CM, Heggebø R, Espenes A, 2004. Involvement of gut-associated lymphoid tissue of ruminants in the spread of transmissible spongiform encephalopathies. Advanced Drug Delivery Reviews, 56(6):885-899.</ref>. PrPSc eventually spreads to most lymph nodes and the central nervous system (CNS). PrPSc can be found in the lymphoreticular system tissues for months before it is found in the brain <ref name="Eklund et al., 1967">Eklund CM, Kennedy RC, Hadlow WJ, 1967. Pathogenesis of scrapie virus infection in the mouse. Journal of Infectious Diseases, 117(1):15-22.</ref>, <ref name="Hadlow et al., 1974"> Hadlow W, Eklund CM, Kennedy RC, Jackson TA, Whitford HW, Boyle CC, 1974. Course of experimental scrapie virus infection in the goat. Journal of Infectious Diseases, 129(5):559-567.</ref>, <ref name="Hadlow et al., 1982"> Hadlow W, Kennedy RC, Race RE, 1982. Natural infection of Suffolk sheep with scrapie virus. Journal of Infectious Diseases, 146(5):657-664.</ref>, <ref name="Hadlow et al., 1980"> Hadlow WJ, Kennedy RC, Race RE, Eklund CM, 1980. Virologic and neurohistologic findings in dairy goats affected with natural scrapie. Veterinary Pathology, 17(2):187-199.</ref>; <ref name="Hadlow et al., 1979"> Hadlow WJ, Race RE, Kennedy RC, Eklund CM, 1979. Natural infection of sheep with scrapie virus. Slow transmissible diseases of the nervous system. Volume 2., 3-12; 5 ref.</ref>. Affected animals may live one to six months after onset of clinical signs <ref name="Capucchio et al., 2001">Capucchio MT, Guarda F, Pozzato N, Coppolino S, Caracappa S, Marco Vdi, 2001. Clinical signs and diagnosis of scrapie in Italy: a comparative study in sheep and goats. Journal of Veterinary Medicine. Series A, 48(1):23-31; 11 ref.</ref>, <ref name="Foster et al., 2001a "> Foster J, Goldmann W, Parnham D, Chong A, Hunter N, 2001a. Partial dissociation of PrP deposition and vacuolation in the brains of scrapie and BSE experimentally affected goats. Journal of General Virology, 82(1):267-273; 30 ref.</ref> , <ref name="Foster et al., 2001b ">Foster JD et al., 2001b. Clinical signs, histopathology and genetics of experimental transmission of BSE and natural scrapie to sheep and goats. Vet. Rec., 148:165-171.</ref>,<ref name="Foster et al., 2001c "> Foster JD, Parnham D, Chong A, Goldmann W, Hunter N, 2001c. Clinical signs, histopathology and genetics of experimental transmission of BSE and natural scrapie to sheep and goats. Veterinary Record, 148(6):165-171; 22 .</ref>, <ref name="USDA, 2005."> USDA, 2005. Scrapie program. http://www.aphis.usda.gov/vs/nahps/scrapie/, accessed 7 March 2005. </ref>.
  
The original source of disease is thought to have come from imported Merino sheep from Spain  <ref name="Parry and Oppenheimer, 1983">Parry HB, Oppenheimer DR, 1983. Scrapie disease in sheep. Historical, clinical, epidemiological, pathological and practical aspects of the natural disease. Scrapie disease in sheep. Historical, clinical, epidemiological, pathological and practical aspects of the natural disease., xvi + 192pp.; 341 ref.</ref>; <ref name="Stockman, 1913 " />, and spread through the movement of of scrapie-infected preclinical sheep <ref name="Brash, 1952"> Brash AG, 1952. Scrapie in imported sheep in New Zealand. New Zealand Veterinary Journal, 1(2):27-30.</ref>; <ref name="Bull and Murnane, 1958"> Bull LB, Murnane D, 1958. An outbreak of scrapie in British sheep imported into Victoria. Australian Veterinary Journal, 34:213-215.</ref>; <ref name="Cooper, 1973"> Cooper JE, 1973. A report of scrapie in sheep in Kenya. British Veterinary Journal, 129(2):13-16.</ref>; <ref name="Parry and Oppenheimer, 1983" />; <ref name="Merwe, 1966"> Merwe GF van der, 1966. The first occurrence of scrapie in the Republic of South Africa. Journal of South African Veterinary Medical Association, 37(4):415-418.</ref>. Scrapie is now endemic throughout Europe and most other continents <ref name="Detwiler and Baylis, 2003"> Detwiler LA, Baylis M, 2003. The epidemiology of scrapie. Revue Scientifique et Technique Office International des Epizooties, 22(1):121-143.</ref>; <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>. It has also been reported in goats <ref name="Andrews et al., 1992">Andrews AH, Laven R, Matthews JG, 1992. Clinical observations on four cases of scrapie in goats. Veterinary Record, 130(5):101; 9 ref.</ref>; <ref name="Brotherston et al., 1968"> Brotherston JG, Renwick CC, Stamp JT, Zlotnik I, 1968. Spread of scrapie by contact to goats and sheep. Journal of Comparative Pathology, 78(1):9-17.</ref>; <ref name="Capucchio et al., 1998; "> Capucchio MT, Guarda F, Isaia MC, Caracappa S, DiMarco V, 1998. Natural occurence of scrapie in goats in Italy. Veterinary Record, 143(16):452-453. .</ref>, <ref name="Chelle, 1942"/>; <ref name="Fankhauser et al., 1982"> Fankhauser R, Vandevelde M, Zwahlen R, 1982. Scrapie in Switzerland? Schweizer Archiv Für Tierheilkunde, 124(5):227-232.</ref>;<ref name="Harcourt, 1974"> Harcourt RA, 1974. Naturally occurring scrapie in goats. Veterinary Record, 94(22):504.</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>; <ref name="Leontides et al., 2000"> Leontides S et al., 2000. A survey of more than 11 years of neurologic diseases of ruminants with special reference to transmissible spongiform encephalopathies (TSEs) in Greece. Journal of Veterinary Medicine. Series B, 47:303-309.</ref>; <ref name="Stemshorn, 1975"> Stemshorn BW, 1975. Un cas de tremblante naturelle chez une chévre. Canadian Veterinary Journal, 16(3):84-86.</ref>; <ref name="Toumazos, 1991"> Toumazos P, 1991. Scrapie in Cyprus. British Veterinary Journal, 147(2):147-154; 11 ref.</ref>; <ref name="Toumazos and Alley, 1989. "> Toumazos P, Alley MR, 1989. Scrapie in goats in Cyprus. New Zealand Veterinary Journal, 37(4):160-162; 11 ref.</ref>  Only Australia and New Zealand are recognized as being currently free of scrapie.
+
The original source of disease is thought to have come from imported Merino sheep from Spain  <ref name="Parry and Oppenheimer, 1983">Parry HB, Oppenheimer DR, 1983. Scrapie disease in sheep. Historical, clinical, epidemiological, pathological and practical aspects of the natural disease. Scrapie disease in sheep. Historical, clinical, epidemiological, pathological and practical aspects of the natural disease., xvi + 192pp.; 341 ref.</ref>, <ref name="Stockman, 1913 " />, and spread through the movement of of scrapie-infected preclinical sheep <ref name="Brash, 1952"> Brash AG, 1952. Scrapie in imported sheep in New Zealand. New Zealand Veterinary Journal, 1(2):27-30.</ref>, <ref name="Bull and Murnane, 1958"> Bull LB, Murnane D, 1958. An outbreak of scrapie in British sheep imported into Victoria. Australian Veterinary Journal, 34:213-215.</ref>, <ref name="Cooper, 1973"> Cooper JE, 1973. A report of scrapie in sheep in Kenya. British Veterinary Journal, 129(2):13-16.</ref>, <ref name="Parry and Oppenheimer, 1983" />, <ref name="Merwe, 1966"> Merwe GF van der, 1966. The first occurrence of scrapie in the Republic of South Africa. Journal of South African Veterinary Medical Association, 37(4):415-418.</ref>. Scrapie is now endemic throughout Europe and most other continents <ref name="Detwiler and Baylis, 2003"> Detwiler LA, Baylis M, 2003. The epidemiology of scrapie. Revue Scientifique et Technique Office International des Epizooties, 22(1):121-143.</ref>, <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>. It has also been reported in goats <ref name="Andrews et al., 1992">Andrews AH, Laven R, Matthews JG, 1992. Clinical observations on four cases of scrapie in goats. Veterinary Record, 130(5):101, 9 ref.</ref>, <ref name="Brotherston et al., 1968"> Brotherston JG, Renwick CC, Stamp JT, Zlotnik I, 1968. Spread of scrapie by contact to goats and sheep. Journal of Comparative Pathology, 78(1):9-17.</ref>; <ref name="Capucchio et al., 1998">Capucchio MT, Guarda F, Isaia MC, Caracappa S, DiMarco V, 1998. Natural occurence of scrapie in goats in Italy. Veterinary Record, 143(16):452-453. .</ref>, <ref name="Chelle, 1942"/>, <ref name="Fankhauser et al., 1982"> Fankhauser R, Vandevelde M, Zwahlen R, 1982. Scrapie in Switzerland? Schweizer Archiv Für Tierheilkunde, 124(5):227-232.</ref>;<ref name="Harcourt, 1974"> Harcourt RA, 1974. Naturally occurring scrapie in goats. Veterinary Record, 94(22):504.</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>; <ref name="Leontides et al., 2000"> Leontides S et al., 2000. A survey of more than 11 years of neurologic diseases of ruminants with special reference to transmissible spongiform encephalopathies (TSEs) in Greece. Journal of Veterinary Medicine. Series B, 47:303-309.</ref>, <ref name="Stemshorn, 1975"> Stemshorn BW, 1975. Un cas de tremblante naturelle chez une chévre. Canadian Veterinary Journal, 16(3):84-86.</ref>; <ref name="Toumazos, 1991"> Toumazos P, 1991. Scrapie in Cyprus. British Veterinary Journal, 147(2):147-154; 11 ref.</ref>, <ref name="Toumazos and Alley, 1989. "> Toumazos P, Alley MR, 1989. Scrapie in goats in Cyprus. New Zealand Veterinary Journal, 37(4):160-162; 11 ref.</ref>. Only Australia and New Zealand are recognized as being currently free of scrapie.
  
 
==Signalment==  
 
==Signalment==  

Revision as of 21:37, 7 June 2011

Also known as: TSE – Transmissible spongiform encephalopathy, Paraplexia enzootica ovium

Introduction

Scrapie was first described in the UK in 1732 [1], [2], and recognised as an infectious disease in 1936 [3], [4]. It is a progressive, fatal and non-febrile neurological disorder affecting sheep and goats. It belongs to a group of diseases called transmissible spongiform encephalopathy (TSE) and 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. 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 PrPsc that it causes degeneration of neurological tissue. The disease causes astrocyte proliferation and then vacuolization of neurons but demyelination does not occur [5]. The abnormal protein is thought to act as a catalyst to convert more of the host’s protein into this abnormal form. 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 [6], [7],[8], [9]. Studies on the spread of scrapie infectivity have suggested that after oral intake, PrPSc first accumulates in Peyer’s patches of the small intestine, gut-associated lymphoid tissues (GALT) and ganglia of the enteric nervous system [10],[11], [12], [13], [14]. PrPSc then moves onward to the tonsil, spleen, retropharyngeal lymph nodes, mesenteric lymph nodes, and peripheral nervous tissue [15], [16],[17]. PrPSc eventually spreads to most lymph nodes and the central nervous system (CNS). PrPSc can be found in the lymphoreticular system tissues for months before it is found in the brain [18], [19], [20], [21]; [22]. Affected animals may live one to six months after onset of clinical signs [23], [24] , [25],[26], [27].

The original source of disease is thought to have come from imported Merino sheep from Spain [28], [29], and spread through the movement of of scrapie-infected preclinical sheep [30], [31], [32], [28], [33]. Scrapie is now endemic throughout Europe and most other continents [34], [35]. It has also been reported in goats [36], [37]; [38], [3], [39];[40], [41]; [42], [43]; [44], [45]. Only Australia and New Zealand are recognized as being currently free of scrapie.

Signalment

Scrapie has a long incubation period of two to five years [29] and affects the majority of sheep between 3 and 5 years of age. It is able to withstand a high degree of heat and high concentrations of formaldehyde [46]; [47] and unlike BSE is influenced by breed and genetic variations among sheep influence infectivity and the incubation period of scrapie. Research has shown that amino acid changes in at least three locations on the PrP gene (codons 136, 154, and 171), have been shown to confer increased or decreased susceptibility to scrapie [48]; [49]; [50]; [51]; Cite error: Closing </ref> missing for <ref> tag; [52], [53] , [54],; [55],, [56],, [57],, [58], [59],; [60],; [61],[62],[63],[64],[65], [66],. The disease has been shown to be effectively transmitted during lambing [67]; [41] as placenta and possibly the placental fluids are thought to be a source of infection [68]; [69]; [70]; [71]; [72] and experimental studies have shown that oral dosing of infected placenta can spread the disease in sheep and goats [73].

Clinical Signs

Early clinical signs may include subtle behavioural changes such as staring or fixed gaze, teeth grinding (bruxism), fine tremor, and hyperaesthesia to sound or sudden movements. Affected animals may later become intolerant to exercise and develop ataxia (awkwardness at turning, swaying of the hindquarters and some 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 and may lead to wool loss (especially over the hindquarters and lateral thorax). A characteristic lip smacking or nibbling reflex can often be elicited by scratching over the lumbar region. In later stages there can be significant weight loss even without a noticeable decrease in appetite, weakness, recumbency, and death. [74], [75]; [76]; [77], [28]; [78]. It is important to note that some scrapie-infected sheep may appear healthy until stressed by transport, shearing, or pregnancy [34].

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 [79]; [80] 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 [81]; [82]. In most instances the abnormal prion is resistant to protein kinase digestion, a feature used in diagnostic techniques.

 PrPSc from post-mortem brainstem or lymphoid tissues may be detected by Western immunoblot analysis [83]; [84]; [85] and immunohistochemistry (IHC) [86] [87]; [88]; [89], [90] . Transmission to mice by injecting suspect tissue can be used to assay infectivity [35]tonsil [91]; [92] and lymphoid biopsies [93]; [94]; [95]; [88]; [96] stained for  PrPsc 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 PrPRes (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 PrPRes carried out following denaturation and concentration steps (Bio-Rad test)[97]

‘’’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 [35]; [78]

Treatment

Scrapie is a fatal condition and no effective treatment is currently available

Control

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 destroyed immediately. 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 [98] [99]; [97]; [100]. 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. The UK government control programme (National Scrapie Plan or NSP) was launched in 2001 and proposes to increase the frequency of the ARR allele in the UK sheep population [101] . Many countries use a combination of genetic selection, depopulation of infected sources and sourcing scrapie free flocks to control the spread of scrapie [100] and [102]

Meat- and bone meal-contaminated feeds have not been shown to be involved in scrapie transmission, but prohibiting the use of feeds that contain ruminant animal products in sheep and goats is a prudent measure. In the UK, a feed ban was issued in 1988 prohibiting the feeding of ruminant-derived meat and bone meal to ruminants (HMSO, 2002) and was adopted by the EU in 1994 and USA in 1997 [97]; [103].

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