Changes

==Signalment==  

==Signalment==  

Scrapie has a long incubation period of two to five years <ref name="Stockman, 1913"/> and affects the majority of sheep between 3 and 5 years of age.  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>. It is able to withstand a high degree of heat and high concentrations of formaldehyde <ref name="Pattison, 1965"> Pattison IH, 1965. Resistance of the scrapie agent to formalin. Journal of Comparative Pathology, 75(Apr):159-164.</ref>, <ref name="Stamp et al., 1959 "> Stamp JJB, Zlotnik I, Mackay J, Smith W, 1959. Further studies on scrapie. Journal of Comparative Pathology, 69(Jul):268-80.</ref> 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 <ref name="Belt et al., 1995">Belt PBGM, Muileman IH, Schreuder BEC, Bos-de Ruijter J, Gielkens ALJ, Smits MA, 1995. Identification of five allelic variants of the sheep PrP gene and their association with natural scrapie. Journal of General Virology, 76(3):509-517, 33 ref. </ref>, <ref name="Billinis et al., 2004"> Billinis C, Psychas V, Leontides L, Spyrou V, Argyroudis S, Vlemmas I, Leontides S, Sklaviadis T, Papadopoulos O, 2004. Prion protein gene polymorphisms in healthy and scrapie-affected sheep in Greece. Journal of General Virology, 85(2):547-554.</ref>, <ref name="Clouscard et al., 1995">Clouscard C, Beaudry P, Elsen JM, Milan D, Dussaucy M, Bounneau C, Schelcher F, Chatelain J, Launay JM, Laplanche JL, 1995. Different allelic efforts of the codons 136 and 171 of the prion protein gene in sheep with natural scrapie. Journal of General Virology, 76(8):2097-2101, 19 ref. </ref>, <ref name="Elsen et al., 1999">Elsen JM, Amigues Y, Schelcher F, Ducrocq V, Andreoletti O, Eychenne F, Khang JVT, Poivey JP, Lantier F, Laplanche JL, 1999. Genetic susceptibility and transmission factors in scrapie: detailed analysis of an epidemic in a closed flock of Romanov. Archives of Virology, 144(3):431-445; 34 ref.</ref>, <ref name="Goldmann et al., 1991">, <ref name="Goldmann et al., 1990">Goldmann W, Hunter N, Benson G, Foster JD, Hope J, 1991. Different scrapie-associated fibril proteins (PrP) are encoded by lines of sheep selected for different alleles of the Sip gene. Journal of General Virology, 72(10):2411-2417, 46 ref.</ref>, <ref name="Goldmann et al., 1994a">Goldmann W, Hunter N, Smith G, Foster J, Hope J, 1994a. PrP genotype and agent effects in scrapie: change in allelic interaction with different isolates of agent in sheep, a natural host of scrapie. Journal of General Virology, 75(5):989-995; 29 ref. </ref>, <ref name="Goldmann et al., 1994b"> Goldmann W, Hunter N, Smith G, Foster J, Hope J, 1994b. PrP genotypes and the Sip gene in Cheviot sheep form the basis for scrapie strain typing in sheep. Annals of the New York Academy of Sciences, 724(Jun 6):296-299. </ref>, <ref name="Hunter and Cairns, 1998">Hunter N, Cairns D, 1998. Scrapie-free Merino and Poll Dorset sheep from Australia and New Zealand have normal frequencies of scrapie-susceptible PrP genotypes. Journal of General Virology, 79(8):2079-2082; 17 ref.</ref>, <ref name="Hunter et al., 1997a ">Hunter N, Goldmann W, Foster JD, Cairns D, Smith G, 1997a. Natural scrapie and PrP genotype: case-control studies in British sheep. Veterinary Record, 141(6):137-140; 15 ref.</ref>, <ref name="Hunter et al., 1997b ">Hunter N, Moore L, Hosie BD, Dingwall WS, Greig A, 1997b. Association between natural scrapie and PrP genotype in a flock of Suffolk sheep in Scotland. Veterinary Record, 140(3):59-63, 20 ref.</ref>, <ref name="Hunter et al., 1997c ">Hunter N, Cairns D, Foster JD, Smith G, Goldmann W, Donnelly K, 1997c. Is scrapie solely a genetic disease?. Nature (London), 386(6621):137; 10 ref.</ref>, <ref name="Hunter et al., 1991, ">Hunter N, Foster JD, Benson G, Hope J, 1991. Restriction fragment length polymorphisms of the scrapie-associated fibril protein (PrP) gene and their association with susceptibility to natural scrapie in British sheep. Journal of General Virology, 72(6):1287-1292; 19 ref.</ref>, <ref name= "Hunter et al., 1996">Hunter N, Foster JD, Goldmann W, Stear MJ, Hope J, Bostock C, 1996. Natural scrapie in a closed flock of Cheviot sheep occurs only in specific PrP genotypes. Archives of Virology, 141(5):809-824, 32 ref.</ref>, <ref name="Hunter et al., 1992">Hunter N, Foster JD, Hope J, 1992. Natural scrapie in British sheep: breeds, ages and PrP gene polymorphisms. Veterinary Record, 130(18):389-392; 16 ref.</ref>, <ref name="Hunter et al., 1993">Hunter N, Goldmann W, Benson G, Foster JD, Hope J, 1993. Swaledale sheep affected by natural scrapie differ significantly in PrP genotype frequencies from healthy sheep and those selected for reduced incidence of scrapie. Journal of General Virology, 74(6):1025-1031; 24 ref.</ref>, <ref name="Hunter et al., 1994">Hunter N, Goldmann W, Smith G, Hope J, 1994. The association of a codon 136 PrP gene variant with the occurrence of natural scrapie. Archives of Virology, 137(1/2):171-177, 22 ref.</ref>, <ref name="Ikeda et al., 1995">Ikeda T, Horiuchi M, Ishiguro N, Muramatsu Y, Kai-Uwe GD, Shinagawa M, 1995. Amino acid polymorphisms of PrP with reference to onset of scrapie in Suffolk and Corriedale sheep in Japan. Journal of General Virology, 76(10):2577-2581; 18 ref.</ref>, <ref name="Thorgeirsdottir et al., 1999">Thorgeirsdottir S, Sigurdarson S, Thorisson HM, Georgsson G, Palsdottir A, 1999. PrP gene polymorphism and natural scrapie in Icelandic sheep. Journal of General Virology, 80(9):2527-2534, 32 ref.</ref>, <ref name="Tranulis et al., 1999">Tranulis MA, Osland A, Bratberg B, Ulvund MJ, 1999. Prion protein gene polymorphisms in sheep with natural scrapie and healthy controls in Norway. Journal of General Virology, 80(4):1073-1077; 23 ref.</ref>, <ref name="Westaway et al., 1994"> Westaway D, Zuliani V, Mirenda Cooper C, Da Costa M, Neuman S, Jenny AL, Detwiler L, Prusiner SB, 1994. Homozygosity for prion protein alleles encoding glutamine-171 renders sheep susceptible to natural scrapie. Genes and Development, 8(8):959-969.</ref>.  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 " />  as placenta and possibly the placental fluids are thought to be a source of infection <ref name="Andréoletti et al., 2002">Andréoletti O, Lacroux C, Chabert A, Monnereau L, Tabouret G, Lantier F, Berthon P, Eychenne F, Lafond-Benestad S, Elsen JM, Schelcher F, 2002. PrP accumulation in placentas of ewes exposed to natural scrapie: influence of foetal PrP genotype and effect on ewe-to-lamb transmission. Journal of General Virology, 83(10):2607-2616; 48 ref.</ref>, <ref name="Onodera et al., 1993"> Onodera T, Ikeda T, Muramatsu Y, Shinagawa M, 1993. Isolation of scrapie agent from the placenta of sheep with natural scrapie in Japan. Microbiology and Immunology, 37(4):311-316. </ref>, <ref name="Race et al., 1998">Race R, Jenny A, Sutton D, 1998. Scrapie infectivity and proteinase K-resistant prion protein in sheep placenta, brain, spleen, and lymph node: implications for transmission and antemortem diagnosis. Journal of Infectious Diseases, 178(4):949-953; 29 ref. </ref>, <ref name="Tuo et al., 2002">Tuo WB, O'Rourke KI, Zhuang DY, Cheevers WP, Spraker TR, Knowles DP, 2002. Pregnancy status and fetal prion genetics determine PrP accumulation in placentomes of scrapie-infected sheep. Proceedings of the National Academy of Sciences of the United States of America, 99(9):6310-6315; 31 ref. </ref>, <ref name="Tuo et al., 2001">Tuo W, Zhuang D, Knowles DP, Cheevers WP, Sy M-S, O’Rourke K, 2001. PrP-C and PrP-Sc at the fetal-maternal interface. Journal of Biological Chemistry, 276(21):18229-18234.</ref> and experimental studies have shown that oral dosing 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 temepratures and concentrations of formaldehyde.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 <ref name="Belt et al., 1995">Belt PBGM, Muileman IH, Schreuder BEC, Bos-de Ruijter J, Gielkens ALJ, Smits MA, 1995. Identification of five allelic variants of the sheep PrP gene and their association with natural scrapie. Journal of General Virology, 76(3):509-517, 33 ref. </ref>, <ref name="Billinis et al., 2004"> Billinis C, Psychas V, Leontides L, Spyrou V, Argyroudis S, Vlemmas I, Leontides S, Sklaviadis T, Papadopoulos O, 2004. Prion protein gene polymorphisms in healthy and scrapie-affected sheep in Greece. Journal of General Virology, 85(2):547-554.</ref>, <ref name="Clouscard et al., 1995">Clouscard C, Beaudry P, Elsen JM, Milan D, Dussaucy M, Bounneau C, Schelcher F, Chatelain J, Launay JM, Laplanche JL, 1995. Different allelic efforts of the codons 136 and 171 of the prion protein gene in sheep with natural scrapie. Journal of General Virology, 76(8):2097-2101, 19 ref. </ref>, <ref name="Elsen et al., 1999">Elsen JM, Amigues Y, Schelcher F, Ducrocq V, Andreoletti O, Eychenne F, Khang JVT, Poivey JP, Lantier F, Laplanche JL, 1999. Genetic susceptibility and transmission factors in scrapie: detailed analysis of an epidemic in a closed flock of Romanov. Archives of Virology, 144(3):431-445; 34 ref.</ref>, <ref name="Goldmann et al., 1991">, <ref name="Goldmann et al., 1990">Goldmann W, Hunter N, Benson G, Foster JD, Hope J, 1991. Different scrapie-associated fibril proteins (PrP) are encoded by lines of sheep selected for different alleles of the Sip gene. Journal of General Virology, 72(10):2411-2417, 46 ref.</ref>, <ref name="Goldmann et al., 1994a">Goldmann W, Hunter N, Smith G, Foster J, Hope J, 1994a. PrP genotype and agent effects in scrapie: change in allelic interaction with different isolates of agent in sheep, a natural host of scrapie. Journal of General Virology, 75(5):989-995; 29 ref. </ref>, <ref name="Goldmann et al., 1994b"> Goldmann W, Hunter N, Smith G, Foster J, Hope J, 1994b. PrP genotypes and the Sip gene in Cheviot sheep form the basis for scrapie strain typing in sheep. Annals of the New York Academy of Sciences, 724(Jun 6):296-299. </ref>, <ref name="Hunter and Cairns, 1998">Hunter N, Cairns D, 1998. Scrapie-free Merino and Poll Dorset sheep from Australia and New Zealand have normal frequencies of scrapie-susceptible PrP genotypes. Journal of General Virology, 79(8):2079-2082; 17 ref.</ref>, <ref name="Hunter et al., 1997a ">Hunter N, Goldmann W, Foster JD, Cairns D, Smith G, 1997a. Natural scrapie and PrP genotype: case-control studies in British sheep. Veterinary Record, 141(6):137-140; 15 ref.</ref>, <ref name="Hunter et al., 1997b ">Hunter N, Moore L, Hosie BD, Dingwall WS, Greig A, 1997b. Association between natural scrapie and PrP genotype in a flock of Suffolk sheep in Scotland. Veterinary Record, 140(3):59-63, 20 ref.</ref>, <ref name="Hunter et al., 1997c ">Hunter N, Cairns D, Foster JD, Smith G, Goldmann W, Donnelly K, 1997c. Is scrapie solely a genetic disease?. Nature (London), 386(6621):137; 10 ref.</ref>, <ref name="Hunter et al., 1991, ">Hunter N, Foster JD, Benson G, Hope J, 1991. Restriction fragment length polymorphisms of the scrapie-associated fibril protein (PrP) gene and their association with susceptibility to natural scrapie in British sheep. Journal of General Virology, 72(6):1287-1292; 19 ref.</ref>, <ref name= "Hunter et al., 1996">Hunter N, Foster JD, Goldmann W, Stear MJ, Hope J, Bostock C, 1996. Natural scrapie in a closed flock of Cheviot sheep occurs only in specific PrP genotypes. Archives of Virology, 141(5):809-824, 32 ref.</ref>, <ref name="Hunter et al., 1992">Hunter N, Foster JD, Hope J, 1992. Natural scrapie in British sheep: breeds, ages and PrP gene polymorphisms. Veterinary Record, 130(18):389-392; 16 ref.</ref>, <ref name="Hunter et al., 1993">Hunter N, Goldmann W, Benson G, Foster JD, Hope J, 1993. Swaledale sheep affected by natural scrapie differ significantly in PrP genotype frequencies from healthy sheep and those selected for reduced incidence of scrapie. Journal of General Virology, 74(6):1025-1031; 24 ref.</ref>, <ref name="Hunter et al., 1994">Hunter N, Goldmann W, Smith G, Hope J, 1994. The association of a codon 136 PrP gene variant with the occurrence of natural scrapie. Archives of Virology, 137(1/2):171-177, 22 ref.</ref>, <ref name="Ikeda et al., 1995">Ikeda T, Horiuchi M, Ishiguro N, Muramatsu Y, Kai-Uwe GD, Shinagawa M, 1995. Amino acid polymorphisms of PrP with reference to onset of scrapie in Suffolk and Corriedale sheep in Japan. Journal of General Virology, 76(10):2577-2581; 18 ref.</ref>, <ref name="Thorgeirsdottir et al., 1999">Thorgeirsdottir S, Sigurdarson S, Thorisson HM, Georgsson G, Palsdottir A, 1999. PrP gene polymorphism and natural scrapie in Icelandic sheep. Journal of General Virology, 80(9):2527-2534, 32 ref.</ref>, <ref name="Tranulis et al., 1999">Tranulis MA, Osland A, Bratberg B, Ulvund MJ, 1999. Prion protein gene polymorphisms in sheep with natural scrapie and healthy controls in Norway. Journal of General Virology, 80(4):1073-1077; 23 ref.</ref>, <ref name="Westaway et al., 1994"> Westaway D, Zuliani V, Mirenda Cooper C, Da Costa M, Neuman S, Jenny AL, Detwiler L, Prusiner SB, 1994. Homozygosity for prion protein alleles encoding glutamine-171 renders sheep susceptible to natural scrapie. Genes and Development, 8(8):959-969.</ref>.  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 " />  as placenta and possibly the placental fluids are thought to be a source of infection <ref name="Andréoletti et al., 2002">Andréoletti O, Lacroux C, Chabert A, Monnereau L, Tabouret G, Lantier F, Berthon P, Eychenne F, Lafond-Benestad S, Elsen JM, Schelcher F, 2002. PrP accumulation in placentas of ewes exposed to natural scrapie: influence of foetal PrP genotype and effect on ewe-to-lamb transmission. Journal of General Virology, 83(10):2607-2616; 48 ref.</ref>, <ref name="Onodera et al., 1993"> Onodera T, Ikeda T, Muramatsu Y, Shinagawa M, 1993. Isolation of scrapie agent from the placenta of sheep with natural scrapie in Japan. Microbiology and Immunology, 37(4):311-316. </ref>, <ref name="Race et al., 1998">Race R, Jenny A, Sutton D, 1998. Scrapie infectivity and proteinase K-resistant prion protein in sheep placenta, brain, spleen, and lymph node: implications for transmission and antemortem diagnosis. Journal of Infectious Diseases, 178(4):949-953; 29 ref. </ref>, <ref name="Tuo et al., 2002">Tuo WB, O'Rourke KI, Zhuang DY, Cheevers WP, Spraker TR, Knowles DP, 2002. Pregnancy status and fetal prion genetics determine PrP accumulation in placentomes of scrapie-infected sheep. Proceedings of the National Academy of Sciences of the United States of America, 99(9):6310-6315; 31 ref. </ref>, <ref name="Tuo et al., 2001">Tuo W, Zhuang D, Knowles DP, Cheevers WP, Sy M-S, O’Rourke K, 2001. PrP-C and PrP-Sc at the fetal-maternal interface. Journal of Biological Chemistry, 276(21):18229-18234.</ref> and experimental studies have shown that oral dosing 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==