- Original article
- Open Access
Bovine Spongiform Encephalopathy (BSE) – Infectious, Contagious, Zoonotic or Production Disease?
- Marcus G. Doherr1
© The Author(s); licensee BioMed Central Ltd. 2003
- Published: 31 March 2003
In 1986, a new progressive neurological condition similar to scrapie of sheep and goats was recognised in cattle in the United Kingdom (UK), and was named bovine spongiform encephalopathy (BSE). There is an ongoing discussion whether BSE should be classified as infectious, contagious, or zoonotic, and if it fits the definition of a production disease. The objective of this work is to briefly describe the main characteristics of transmissible spongiform encephalopathies (TSE), to review the epidemiology of BSE, and to address the question of how to classify BSE. TSEs are characterised as chronic wasting diseases with spongiform vacuolation and the accumulation of infectious prion protein (PrPSc) in the central nervous system. TSE infectivity is very difficult to inactivate. Cattle BSE most likely originated from sheep scrapie, although this will remain to be an issue for debate. The disease can be transmitted from cattle to a range of species, and has resulted in smaller TSE epidemics in domestic cats, zoo cats and zoo ruminants, and in humans. Transmission in the field occurred through feed containing ruminant-derived protein, and measures to prevent the recycling of infectivity have proven effective to reduce the number of new infections. Mandatory reporting of clinical suspects combined with targeted screening of risk populations is needed to assess the BSE status of a country. Infection studies and the transmissibility to other species classify BSE as infectious and zoonotic. Absence of excretion of the agent, and therefor of horizontal transmission, categorise BSE as non-contagious. However, BSE is a multifactorial infectious disease that is dependent on management factors (mainly feeding), and therefore fits into the broader definition of production diseases.
- Spongiform encephalopathy
- production disease
In 1986, a new clinical disease in cattle was recognised in the United Kingdom (UK). It was classified as a progressive neurological condition similar to scrapie of sheep and goats, and was named bovine spongiform encephalopathy (BSE) . Other transmissible spongiform encephalopathies (TSE) had been described before the occurrence of BSE, namely scrapie of sheep and goats (first observed/described as a clinical entity around 1730), a transmissible mink encephalopathy (TME, 1947), a chronic wasting disease of North American deer and elk (CWD, 1978), and the human TSEs sporadic Creutzfeldt-Jakob disease (sCJD, 1920), Gerstmann-Sträussler-Scheinker Syndrom (GSS, 1928), Kuru (1957), and fatal familiar insomnia (FFI, 1986). These TSEs can arise spontaneously (sCJD), be inherited (FFI, GSS), or are naturally or accidentally transmitted (scrapie, Kuru, CWD, BSE). Some of them possess several of these properties [16, 9, 22, 59, 57, 20, 41, 31]. There is an ongoing discussion whether BSE should be classified as infectious, contagious, or zoonotic, and if it fits the definition of a production disease. The objective of this work is to briefly describe the main characteristics of TSEs, to review the epidemiology of BSE, and to address the question of how to classify BSE.
All known TSEs are characterised by an accumulation of prions ("proteinacious infectious particles", PrP) and vacuolation of the CNS in the final stages of the disease. PrPC is routinely synthesised by various cells, and is metabolised (digested) by proteinase K (enzymes). The infectious prion protein, denoted PrPSc or PrPres, is partly proteinase K resistant. It forms oligomers, accumulates mainly in the cells of the CNS, and results in the specific histopathological changes observed in the differed TSEs . Both PrPC and PrPSc have the same aminoacid sequence, but they have different three-dimensional structures: PrPC in 42% is composed of structures called alpha helices, and has only a few beta sheets . The infectious PrPSc has only 30% alpha helices, and more than 40% beta sheets. The transition of PrPC to PrPSc, based on the prion dimer theory of Prusiner, occurs by merging of a normal (healthy) and an infectious prion molecule to form a PrPC-PrPSc heterodimer, in which the normal PrPC molecule is restructured into PrPSc. After separation of the 2 molecules, 2 new PrPSc homodimers have been created which again can convert healthy PrPC molecules . It still is debated whether PrPSc and TSE infectivity are one and the same, or if there is an additional factor "X" (protein, virion, virus?) besides exposure to PrPSc required to result in a TSE infection .
TSE infectivity is difficult to destroy (decontaminate). The most efficient method is application of wet heat (autoclaving) after treatment with sodium hydroxide (1–2 M NaOH). Application of dry heat will conserve TSE infectivity, and temperatures up to 600°C have been described as insufficient to fully eliminate it from brain tissue cubes [3, 5]. The commonly used methods to treat MBM during rendering (133°C at 3 bars for 20 minutes) will reduce TSE infectivity by at least 98%, but not always by 100% [43, 45, 38, 44, 46]. TSE infectivity, once excreted, can survive in the environment (soil) for several years, as has been demonstrated with the scrapie agent .
The origin of BSE (as a cattle disease) is an issue of controversial debate, but it is unlikely that this controversy will ever be resolved. The most widely accepted hypothesis is that cattle BSE originated from sheep scrapie, i.e. that one of the British sheep scrapie strains was recycled with MBM to cattle, and was (or became during recycling) infectious for cattle. After this adaptation, on-going intra-species recycling caused the BSE epidemic in British cattle [35, 47]. Alternatively, a spontaneous mutation in the genome coding for the PrP gene, similar to sporadic CJD in humans, could have resulted in a TSE strain either in sheep or in cattle that was subsequently infectious for – and recycled to – cattle. The introduction of BSE from a wildlife population seems to be a less realistic hypothesis. Large scale recycling of BSE infectivity in the UK became possible after 1970 when changes in the tallow (fat) extraction during MBM rendering from solvent-based (wet, higher temperatures) to pressure-based (dry, lower temperatures) allowed the infectious agent to survive [54, 22].
Experimental oral inoculation of calves and sequential slaughter done in the UK documented that BSE infectivity was only present in the anatomical region of the Peyers patches of the distal ileum at distinct time points during the incubation period, and in the central nervous system (CNS: brain, spinal cord, dorsal root ganglia) late in incubation (few months before clinical disease) and during clinical disease. In cattle, BSE infectivity has not been documented in meat, milk, blood, urine, lymph nodes or any other tissue besides the CNS and the distal ileum wall [25, 42, 51, 52]. One report in which sternal bone marrow isolated from a clinical BSE case in one of the experimentally exposed mice induced a TSE was never reproduced, and was later speculated to have been cross-contamination. Without excretion of the infectious agent during incubation or clinical disease, direct horizontal transmission (from infected to susceptible cattle) does not occur. BSE infectivity levels of CNS tissue from clinically diseased cattle have been titrated in cattle, and there is evidence that 0.1 gram of brain tissue is sufficient to orally infect calves with BSE. Direct intracerebral inoculation of the infectious agent into susceptible mice strains seems to be 500 to 1000 times more efficient than oral exposure of the mice, and this method is used extensively to study the distribution of BSE infectivity in various tissues of experimentally infected animals or field cases, and to differentiate between BSE and other TSE strains.
Implementation of mandatory reporting for bovine spongiform encephalopathy (BSE), year of the first BSE cases, implementation of a targeted screening, total BSE case numbers in 2000 and 2001, and assessment of the overall BSE surveillance system in the European Union Member States and Switzerland as of December 21, 2001.
Adult cattle pop.1
Mandatory reporting since (year)
First reported BSE case (OIE)
Detected BSE cases (OIE)
Surveillance system meets OIE requirements (GBR June 2000)
No data available
Transmission of BSE to other species is possible. This has been documented in experimental infection of several species, but also in the observed FSE epidemic in domestic cats (over 90 cases in the UK reported since 1990), in ruminants and large cats kept in British zoos, and by the epidemic of the new variant of Creutzfeldt-Jakob disease (vCJD) in humans with over 100 cases in the UK and 4 cases reported from France so far [30, 60, 50, 36, 6, 58, 17].
BSE can be orally transmitted to sheep and goats where it results in a TSE very similar to scrapie [14, 15]. No field cases of BSE in sheep have yet been diagnosed, however, differentiation to sheep scrapie is only possible by strain typing in mice bioassays, which takes several years to perform. Attempts to orally infect pigs or poultry with BSE failed so far [7, 13, 24].
BSE is a new disease in cattle. Infectivity can be titrated, and the disease has been transmitted to the same and to other species including cats and humans. This classifies BSE as infectious and zoonotic. However, even cattle in the final stages of (clinical) disease do not actively excrete the infectious agent, and horizontal transmission comparable with that of foot-and-mouth disease (FMD), classical swine fever (CSF) or even sheep scrapie does not occur; the disease therefore is not considered to be contagious. The term "production diseases" traditionally was used exclusively for metabolic diseases that were induced by management practices. More recently, the definition of production diseases has been widened to include other traits such as infertility, and multifactorial diseases such as mastitis and lameness that might involve infectious agents but that are exacerbated by nutritional or management factors . BSE, which is caused by an infectious agent (even though some "infectiologists" might not agree to classify prion diseases as such) and is dependent on management factors, would fit into the broader definition of production diseases. This, however, could be true for the majority of diseases that currently affect our animal production systems.
- Alban L, de Koeijer AA, Heim D, Hueston WD, Kreysa J, Roberts MG: Assessment of the geographical risk of bovine spongiform encephalopathy – a proposal. Proceedings of the 9th Conference of the International Society for Veterinary Epidemiology and Economics, August 6–11, 2000, Breckenridge, Colorado (USA). 2000, , Breckenridge, Colorado (USA)Google Scholar
- Anderson RM, Donnelly CA, Ferguson NM, Woolhouse ME, Watt CJ, Udy HJ, MaWhinney S, Dunstan SP, Southwood TR, Wilesmith JW, Ryan JB, Hoinville LJ, Hillerton JE, Austin AR, Wells GAH: Transmission dynamics and epidemiology of BSE in British cattle. Nature. 1996, 382: 779-788. 10.1038/382779a0.View ArticlePubMedGoogle Scholar
- Brown P, Liberski PP, Wolff A, Gajdusek DC: Resistance of scrapie infectivity to steam autoclaving after formaldehyde fixation and limited survival after ashing at 360 degrees C: practical and theoretical implications. J Infect Dis. 1990, 161 (3): 467-472. 10.1093/infdis/161.3.467.View ArticlePubMedGoogle Scholar
- Brown P, Gajdusek DC: Survival of scrapie virus after 3 years' interment. Lancet. 1991, 337 (8736): 269-270. 10.1016/0140-6736(91)90873-N.View ArticlePubMedGoogle Scholar
- Brown P, Rau EH, Johnson BK, Bacote AE, Gibbs CJJ, Gajdusek DC: New studies on the heat resistance of hamster-adapted scrapie agent: threshold survival after ashing at 600 degrees C suggests an inorganic template of replication. Proc Natl Acad Sci USA. 2000, 97 (7): 3418-3421. 10.1073/pnas.050566797.PubMed CentralPubMedGoogle Scholar
- Collinge J, Sidle KC, Meads J, Ironside J, Hill AF: Molecular analysis of prion strain variation and the aetiology of 'new variant' CJD. Nature. 1996, 383 (6602): 685-690. 10.1038/383685a0.View ArticlePubMedGoogle Scholar
- Dawson M, Wells GAH, Parker BNJ, Scott AC: Primary parenteral transmission of bovine spongiform encephalopathy to the pig. Vet Rec. 1990, 127: 338-PubMedGoogle Scholar
- Deslys JP, Comoy E, Hawkins S, Simon S, Schimmel H, Wells G, Grassi J, Moynagh J: Screening slaughtered cattle for BSE. Nature. 2001, 409 (6819): 476-478. 10.1038/35054134.View ArticlePubMedGoogle Scholar
- Detwiler LA: Scrapie. Rev Sci Tech Off Int Epiz. 1992, 11 (2): 491-537.Google Scholar
- Doherr MG, Oesch B, Moser M, Vandevelde M, Heim D: Targeted surveillance for bovine spongiform encephalopathy. Vet Rec. 1999, 145: 672-View ArticlePubMedGoogle Scholar
- Doherr MG, Heim D, Fatzer R, Cohen CH, Vandevelde M, Zurbriggen A: Targeted screening of high-risk cattle populations for BSE to augment mandatory reporting of clinical suspects. Prev Vet Med. 2001, 51 (1–2): 3-16. 10.1016/S0167-5877(01)00203-3.View ArticlePubMedGoogle Scholar
- Doherr MG, Hett AR, Cohen CH, Fatzer R, Rüfenacht J, Zurbriggen A, Heim D: Trends in prevalence of BSE in Switzerland based on fallen stock and slaughter surveillance. Vet Rec. 2002, 150: 347-348. 10.1136/vr.150.11.347.View ArticlePubMedGoogle Scholar
- Done JT: Spongiform encephalopathy in pigs. Vet Rec. 1990, 127 (19): 484-PubMedGoogle Scholar
- Foster JD, Hope J, Fraser H: Transmission of bovine spongiform encephalopathy to sheep and goats. Vet Rec. 1993, 133 (14): 339-341. 10.1136/vr.133.14.339.View ArticlePubMedGoogle Scholar
- Foster JD, Bruce M, McConnell I, Chree A, Fraser H: Detection of BSE infectivity in brain and spleen of experimentally infected sheep. Vet Rec. 1996, 138 (22): 546-548. 10.1136/vr.138.22.546.View ArticlePubMedGoogle Scholar
- Hartsough GR, Burger D: Encephalopathy of mink. I. Epizootiologic and clinical observations. J Inf Dis. 1965, 115: 387-392. 10.1093/infdis/115.4.387.View ArticleGoogle Scholar
- Hill AF, Desbruslais M, Joiner S, Sidle KC, Gowland I, Collinge J, Doey LJ, Lantos P: The same prion strain causes vCJD and BSE. Nature. 1997, 389 (6650): 448-450. 10.1038/38925.View ArticlePubMedGoogle Scholar
- Hoinville LJ: Decline in the incidence of BSE in cattle born after the introduction of the 'feed ban'. Vet Rec. 1994, 134: 274-275. 10.1136/vr.134.11.274.View ArticlePubMedGoogle Scholar
- Hoinville LJ, Wilesmith JW, Richards MS: An investigation of risk factors for cases of bovine spongiform encephalopathy born after the introduction of the 'feed ban'. Vet Rec. 1995, 136 (13): 312-318. 10.1136/vr.136.13.312.View ArticlePubMedGoogle Scholar
- Hoinville LJ: A review of the epidemiology of scrapie in sheep. Rev Sci Tech Off Int Epiz. 1996, 15 (3): 827-852.Google Scholar
- Hörnlimann B, Guidon D, Griot C: Risikoeinschätzung für die Einschleppung von BSE [Risk assessment for importing bovine spongiform encephalopathy]. Deutsche Tierärztliche Wochenschrift. 1994, 101 (7): 295-298.PubMedGoogle Scholar
- Kimberlin RH: Bovine spongiform encephalopathy. Rev Sci Tech Off Int Epiz. 1992, 11 (2): 347-390.Google Scholar
- Lopez Garcia F, Zahn R, Riek R, Wuthrich K: NMR structure of the bovine prion protein. Proc Natl Acad Sci USA. 2000, 97 (15): 8334-8339. 10.1073/pnas.97.15.8334.PubMed CentralView ArticlePubMedGoogle Scholar
- Meldrum KC: Transmission of BSE to a pig. Vet Rec. 1990, 127: 362-PubMedGoogle Scholar
- Middleton DJ, Barlow RM: Failure to transmit bovine spongiform encephalopathy to mice by feeding them with extraneural tissues of affected cattle. Vet Rec. 1993, 132: 545-547. 10.1136/vr.132.22.545.View ArticlePubMedGoogle Scholar
- Moynagh J, Schimmel H: Tests for BSE evaluated. Nature. 1999, 400 (6740): 105-10.1038/21981.View ArticlePubMedGoogle Scholar
- Nathanson N, Wilesmith JW, Griot C: Bovine spongiform encephalopathy (BSE): causes and consequences of a common source epidemic. Am J Epidemiol. 1997, 145 (11): 959-969. 10.1093/oxfordjournals.aje.a009064.View ArticlePubMedGoogle Scholar
- Nir Markusfeld O: What are production diseases, and how do we manage them?. 11th International Conference on Production Diseases in Farm Animals, 12–16 August 2001, Frederiksberg, Denmark. Acta vet scand. 2003, ???-Suppl 98Google Scholar
- Oesch B, Doherr MG, Heim D, Fischer K, Egli S, Bolliger S, Biffiger K, Schaller O, Vandevelde M, Moser M: Application of Prionics Western blotting procedure to screen for BSE in cattle regularly slaughtered at Swiss abattoirs. Archives Virol [Suppl]. 2000, 16: S189-S195.Google Scholar
- Pearson GR, Gruffydd_Jones TJ, Wyatt JM, Hope J, Chong A, Scott AC, Dawson M, Wells GA: Feline spongiform encephalopathy. Vet Rec. 1991, 128 (22): 532-View ArticlePubMedGoogle Scholar
- Prusiner SB: The prion diseases. Brain Pathology. 1998, 8 (3): 499-513.View ArticlePubMedGoogle Scholar
- Prusiner SB: Prions. Proc Natl Acad Sci USA. 1998, 95 (23): 13363-13383. 10.1073/pnas.95.23.13363.PubMed CentralView ArticlePubMedGoogle Scholar
- Schaller O, Fatzer R, Stack M, Clark J, Cooley W, Biffiger K, Egli S, Doherr M, Vandevelde M, Heim D, Oesch B, Moser M: Validation of a Western immunoblotting procedure for bovine PrPSC detection and its use as a rapid surveillance method for the diagnosis of bovine spongiform encephalopathy (BSE). Acta Neuropathol. 1999, 98 (5): 437-443. 10.1007/s004010051106.View ArticlePubMedGoogle Scholar
- Schiermeier Q: Testing times for BSE. Nature. 2001, 409: 658-659. 10.1038/35055703.View ArticlePubMedGoogle Scholar
- Schreuder BEC: General aspects of transmissible spongiform encephalopathies and hypotheses about the agents. Vet Q. 1993, 15 (4): 167-174. 10.1080/01652176.1993.9694399.View ArticlePubMedGoogle Scholar
- Schreuder BEC: Animal spongiform encephalopathies – an update. Part 1. Scrapie and lesser known animal spongiform encephalopathies. Vet Q. 1994, 16 (3): 174-181. 10.1080/01652176.1994.9694444.View ArticlePubMedGoogle Scholar
- Schreuder BEC, Wilesmith JW, Ryan JBM, Straub OC: Risk of BSE from the import of cattle from the United Kingdom into countries of the European Union. Vet Rec. 1997, 141 (8): 187-190. 10.1136/vr.141.8.187.View ArticlePubMedGoogle Scholar
- Schreuder BEC, Geertsma RE, van Keulen LJ, van Asten JA, Enthoven P, Oberthur RC, de Koeijer AA, Osterhaus AD: Studies on the efficacy of hyperbaric rendering procedures in inactivating bovine spongiform encephalopathy (BSE) and scrapie agents. Vet Rec. 1998, 142 (18): 474-480. 10.1136/vr.142.18.474.View ArticlePubMedGoogle Scholar
- SSC, 2000a: Final Opinion of the Scientific Steering Committee on the Geographical Risk of Bovine Spongiform Encephalopathy (GBR). Opinion of the Scientific Steering Committee of the European Commission (adopted 6 July 2000).Google Scholar
- SSC, 2000b: Commission Decision 2000/374/EC of 5 June 2000 amending Decision 98/272/EC on epidemio-surveillance for transmissible spongiform encephalopathies. Official Journal of the European Communities. 135: 27-35.Google Scholar
- Spraker TR, Miller MW, Williams ES, Getzy DM, Adrian WJ, Schoonveld GG, Spowart RA, O'Rourke KI, Miller JM, Merz PA: Spongiform encephalopathy in free-ranging mule deer (Odocoileus hemionus), white-tailed deer (Odocoileus virginianus) and Rocky Mountain elk (Cervus elaphus nelsoni) in northcentral Colorado. J Wildl Dis. 1997, 33 (1): 1-6.View ArticlePubMedGoogle Scholar
- Taylor DM, Ferguson CE, Bostock CJ, Dawson M: Absence of disease in mice receiving milk from cows with bovine spongiform encephalopathy. Vet Rec. 1995, 136 (23): 592-10.1136/vr.136.23.592.View ArticlePubMedGoogle Scholar
- Taylor DM, Fernie K, McConnell I, Ferguson CE, Steele PJ: Solvent extraction as an adjunct to rendering: the effect on BSE and scrapie agents of hot solvents followed by dry heat and steam. Vet Rec. 1998, 143 (1): 6-9. 10.1136/vr.143.1.6.View ArticlePubMedGoogle Scholar
- Taylor DM: Inactivation of prions by physical and chemical means. J Hosp Infect. 1999, 43 (Suppl): S69-S76. 10.1016/S0195-6701(99)90067-1.View ArticlePubMedGoogle Scholar
- Taylor DM, Fernie K, McConnell I, Steele PJ: Survival of scrapie agent after exposure to sodium dodecyl sulphate and heat. Vet Microbiol. 1999, 67 (1): 13-16. 10.1016/S0378-1135(99)00026-7.View ArticlePubMedGoogle Scholar
- Taylor DM: Inactivation of transmissible degenerative encephalopathy agents: A review. Vet J. 2000, 159 (1): 10-17. 10.1053/tvjl.1999.0406.View ArticlePubMedGoogle Scholar
- Taylor K: Origin of BSE. Vet Rec. 1995, 137 (26): 674-675.PubMedGoogle Scholar
- Telling GC, Scott M, Mastrianni J, Gabizon R, Torchia M, Cohen FE, DeArmond SJ, Prusiner SB: Prion propagation in mice expressing human and chimeric PrP transgenes implicates the intraction of cellular PrP with another protein. Cell. 1995, 83: 79-90. 10.1016/0092-8674(95)90236-8.View ArticlePubMedGoogle Scholar
- Wells GA, Scott AC, Johnson CT, Gunning RF, Hancock RD, Jeffrey M, Dawson M, Bradley R: A novel progressive spongiform encephalopathy in cattle. Vet Rec. 1987, 121 (18): 419-420. 10.1136/vr.121.18.419.View ArticlePubMedGoogle Scholar
- Wells GA, McGill IS: Recently described scrapie-like encephalopathies of animals: case definitions. Res Vet Sci. 1992, 53 (1): 1-10. 10.1016/0034-5288(92)90076-E.View ArticlePubMedGoogle Scholar
- Wells GAH, Dawson M, Hawkins SAC, Green RB, Dexter I, Francis ME, Simmons MM, Austin AR, Horigan MW: Infectivity in the ileum of cattle challenged orally with bovine spongiform encephalopathy. Vet Rec. 1994, 135: 40-41. 10.1136/vr.135.2.40.View ArticlePubMedGoogle Scholar
- Wells GAH, Hawkins SAC, Green RB, Austin AR, Dexter I, Spencer YI, Chaplin MJ, Stack MJ, Dawson M: Preliminary observations on the pathogenesis of experimental bovine spongiform encephalopathy (BSE): an update. Vet Rec. 1998, 142: 103-106. 10.1136/vr.142.5.103.View ArticlePubMedGoogle Scholar
- Wilesmith JW, Wells GAH, Cranwell MP, Ryan JBM: Bovine spongiform encephalopathy: epidemiological studies. Vet Rec. 1988, 123 (25): 638-644.PubMedGoogle Scholar
- Wilesmith JW, Ryan JBM, Atkinson MJ: Bovine spongiform encephalopathy: epidemiological studies on the origin. Vet Rec. 1991, 128: 199-203. 10.1136/vr.128.9.199.View ArticlePubMedGoogle Scholar
- Wilesmith JW, Ryan JB, Hueston WD, Hoinville LJ: Bovine spongiform encephalopathy: epidemiological features 1985 to 1990. Vet Rec. 1992, 130 (5): 90-94. 10.1136/vr.130.5.90.View ArticlePubMedGoogle Scholar
- Wilesmith JW, Ryan JBM, Hueston WD: Bovine spongiform encephalopathy: case-control studies of calf feeding practices and meat and bonemeal inclusion in proprietary concentrates. Res Vet Sci. 1992, 52: 325-331. 10.1016/0034-5288(92)90032-W.View ArticlePubMedGoogle Scholar
- Will RG: Epidemiology of Creutzfeldt-Jakob disease. Br Med Bull. 1993, 49 (4): 960-970.PubMedGoogle Scholar
- Will RG, Ironside JW, Zeidler M, Cousens SN, Estibeiro K, Alperovitch A, Poser S, Pocchiari M, Hofman A, Smith PG: A new variant of Creutzfeldt-Jakob disease in the UK. Lancet. 1996, 347 (9006): 921-5. 10.1016/S0140-6736(96)91412-9.View ArticlePubMedGoogle Scholar
- Williams ES, Young S: Spongiform encephalopathies in Cervidae. Rev Sci Tech Off Int Epiz. 1992, 11 (2): 551-567.Google Scholar
- Wyatt JM, Pearson GR, Smerdon TN, Gruffydd_Jones TJ, Wells GA, Wilesmith JW: Naturally occurring scrapie-like spongiform encephalopathy in five domestic cats. Vet Rec. 1991, 129 (11): 233-236. 10.1136/vr.129.11.233.View ArticlePubMedGoogle Scholar
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