USDA Confirms Detection of Classical Scrapie in a Slaughtered Sheep
USDA Confirms Detection of Classical Scrapie in a Slaughtered Sheep
The U.S. Department of Agriculture’s (USDA) Animal and Plant Health Inspection Service (APHIS) has confirmed classical scrapie in a sheep slaughtered at a facility in Oregon. Final diagnostic results and genotype analysis were completed by the National Veterinary Services Laboratories (NVSL), with confirmatory testing indicating classical scrapie. As required, APHIS has notified the World Organisation for Animal Health (WOAH) of the confirmed detection.
Classical scrapie is a fatal, degenerative prion disease of sheep and goats. Prior to this confirmation, the United States had gone more than 5 years without a case. The United States was positioned to meet WOAH’s 7‑year benchmark for self‑declared scrapie freedom in January 2028. This confirmed detection could reset that timeline and may push the earliest possible date for national scrapie‑free status to approximately 2033.
APHIS and State animal health officials have initiated an epidemiological investigation to determine the flock of origin. The affected animal did not have an ear tag, which may limit traceability and highlights the critical importance of strong animal identification practices nationwide. To support the investigation, NVSL will conduct tissue‑matching and parentage testing on the affected sheep and two additional animals from the same accession.
APHIS expects minimal impact on trade. Most countries restrict live animal exports only from affected flocks or premises, and products such as wool remain unaffected.
USDA encourages producers to reinforce key practices that have advanced scrapie eradication efforts nationwide:
Strict compliance with ear tagging and traceability requirements to ensure exposed animals can be accurately tracked.
Robust surveillance participation, including submission of clinical suspects and routine monitoring.
Use of genetically resistant breeding stock, which significantly reduces disease susceptibility and depopulation needs.
Continued partnership with APHIS and State officials to support investigation and long‑term freedom efforts.
More information about scrapie and APHIS’ eradication program is available at www.aphis.usda.gov.
https://www.aphis.usda.gov/news/program-update/usda-confirms-detection-classical-scrapie-slaughtered-sheep
https://www.aphis.usda.gov/livestock-poultry-disease/sheep-goat/scrapie
July 31, 2026
SCRAPIE TSE Prion USA RAPID RESPONSE URGENT UPDATES DECEMBER 25, 2025
SCRAPIE TSE Prion USA RAPID RESPONSE URGENT UPDATES DECEMBER 25, 2025
ARS Research Project: Elucidating the Pathobiology and Transmission of Transmissible Spongiform Encephalopathies 2025
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Accomplishments
***> 1. 01 Determined that white-tailed deer (WTD) infected with scrapie from sheep can transmit the disease to other deer under conditions mimicking natural exposure. It has long been suggested that prion disease in deer (chronic wasting disease (CWD)) was caused by the prion agent from sheep. The prion disease that affects sheep, scrapie, has been recognized for hundreds of years. However, chronic wasting disease, a similar disease found in WTD, has only been recognized since the 1960s. ARS researchers in Ames, Iowa, showed that white-tailed deer sick with scrapie from sheep can infect other deer under conditions mimicking natural exposure. Furthermore, this work shows that CWD is difficult to differentiate from WTD infected with scrapie. WTD scrapie prions accumulate in the lymphoreticular system in a manner similar to CWD, meaning that environmental contamination may occur through feces, saliva, and other body fluids of scrapie affected WTD as has been shown for CWD. The presence of WTD infected with scrapie could confound mitigation efforts for chronic wasting disease. This information informs regulatory officials, the farmed cervid industry, and officials tasked with protecting animal health such as state Departments of Agriculture, Natural Resources, or Parks and Wildlife with regard to a disease similar to CWD but arising from sheep scrapie that could be present in WTD that have contact with scrapie affected sheep and/or goats.
2. 02 Showed that gene-targeted mice are capable of reproducing strain specific effects typically limited to natural host species of chronic wasting disease (CWD). CWD is a highly contagious disease of deer, elk, moose, and reindeer found in North America, South Korea, and Scandinavian countries that is caused by misfolded proteins called prions. CWD prions transmit through direct contact between infected animals, or through contaminated soil, grass, or water. All prion diseases exhibit progressive neurodegeneration and ultimately death. Scientists typically study CWD by injecting prions into susceptible animals' brains in lab experiments. Intracranial prion injections are favored because they typically produce shorter incubation periods and higher disease attack rates compared to natural infection. ARS researchers in Ames, Iowa, along with university collaborators showed that this inoculation method can cause the prion strains to change in a way that does not accurately reflect how the disease spreads naturally. They found that using a combination of peripheral inoculation (injection outside the brain) in natural hosts and using novel gene-targeted mice generated in a manner that provides a more natural expression of the inserted prion gene that gives a more accurate picture of how CWD behaves in the real world. The novel mouse model provides an important strategy to precisely assess the zoonotic potential (likelihood of transmission from animals to humans) of CWD and other animal prion diseases using natural routes of transmission. This will impact the tools used and direction of future studies of CWD and other prion diseases allowing more rapid and comprehensive responses to emerging questions aiding both the researchers at the producers they support…end
https://www.ars.usda.gov/research/project/?accnNo=440677&fy=202
Title: Characterization of classical sheep scrapie in white-tailed deer after experimental oronasal exposure
Author item Greenlee, Justin item MOORE, SARAH - Orise Fellow item Cassmann, Eric item LAMBERT, ZOE - Orise Fellow item Kokemuller, Robyn item Smith, Jodi item Kunkle, Robert item KONG, QINGZHONG - Case Western Reserve University (CWRU) item WEST GREENLEE, HEATHER - Iowa State University
Submitted to: Journal of Infectious Diseases Publication Type: Peer Reviewed Journal Publication Acceptance Date: 11/4/2022 Publication Date: 11/8/2022
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Technical Abstract: Scrapie is a prion disease of sheep and goats that is associated with widespread accumulation of abnormal prion protein (PrPSc) in the central nervous and lymphoid tissues. Chronic wasting disease (CWD) is the natural prion disease of cervid species and is similar to scrapie in sheep. The purpose of this study was to determine susceptibility of white-tailed deer (WTD) to the scrapie agent. We inoculated WTD (n=5) by a concurrent oral and intranasal exposure with the scrapie agent from sheep and (n=6) with the scrapie agent from goats. All deer exposed to the agent of scrapie from sheep had evidence of PrPSc accumulation. PrPSc was detected in lymphoid tissues at preclinical time points, and deer necropsied after 28 months post-inoculation had clinical signs, spongiform lesions, and widespread distribution of PrPSc in neural and lymphoid tissues. Western blots done on samples from the brainstem, cerebellum, and lymph nodes of scrapie-infected WTD have a molecular profile similar to CWD and distinct from western blots of samples from the cerebral cortex, retina, or the original sheep scrapie inoculum. WTD are susceptible to the agent of scrapie from sheep and differentiation from CWD may be difficult.
https://www.ars.usda.gov/research/publications/publication/?seqNo115=336834
Our findings establish that white-tailed deer are susceptible to WTD scrapie and that the presence of WTD scrapie agent in the lymphoreticular system suggests the handling of suspected cases should be consistent with current CWD guidelines because environmental shedding may occur.
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The potential for zoonoses of cervid-derived PrPSc is still not well understood (6,18,45–47); however, interspecies transmission can increase host range and zoonotic potential (48–50). Therefore, to protect herds and the food supply, suspected cases of WTD scrapie should be handled the same as cases of CWD.
https://wwwnc.cdc.gov/eid/article/30/8/24-0007_article
see;
https://nor-98.blogspot.com/2016/09/goat-k222-prpc-polymorphic-variant-does.html
https://transmissiblespongiformencephalopathy.blogspot.com/2026/04/us-report-scrapie-cwd-cattle-sheep-pigs.html
***> USA Report, Scrapie, CWD, BSE, TSE, Cattle, Sheep, Pigs, Cervid, Humans, Zoonotic, 2026
April 2026
https://fdabse589.blogspot.com/2026/04/usa-report-scrapie-cwd-bse-tse-cattle.html
https://www.researchgate.net/publication/403956772_USA_Report_Scrapie_CWD_BSE_TSE_Cattle_Sheep_Pigs_Cervid_Humans_Zoonotic_2026
Tuesday, June 9, 2026
Hazard identification for the risks to terrestrial animal health from the import of hay and straw, BSE, CWD, Scrapie, TSE, Prion
https://www.gov.uk/government/publications/hazard-identification-for-the-risks-to-terrestrial-animal-health-from-the-import-of-hay-and-straw/hazard-identification-for-the-risks-to-terrestrial-animal-health-from-the-import-of-hay-and-straw
https://defrauktseprp.blogspot.com/2026/06/hazard-identification-for-risks-to.html
Cervid CWD TSE PrP Transmission to Humans, has it already happened and being masked as sporadic CJD, What if? July 2026 Review
https://chronic-wasting-disease.blogspot.com/2026/07/cervid-cwd-tse-prp-transmission-to.html
https://prpsc.proboards.com/thread/224/cervid-transmission-humans-july-review
Transmission of scrapie prions to primate after an extended silent incubation period
*** In complement to the recent demonstration that humanized mice are susceptible to scrapie, we report here the first observation of direct transmission of a natural classical scrapie isolate to a macaque after a 10-year incubation period. Neuropathologic examination revealed all of the features of a prion disease: spongiform change, neuronal loss, and accumulation of PrPres throughout the CNS.
*** This observation strengthens the questioning of the harmlessness of scrapie to humans, at a time when protective measures for human and animal health are being dismantled and reduced as c-BSE is considered controlled and being eradicated.
*** Our results underscore the importance of precautionary and protective measures and the necessity for long-term experimental transmission studies to assess the zoonotic potential of other animal prion strains.
http://www.ars.usda.gov/research/publications/publications.htm?SEQ_NO_115=313160
***Moreover, sporadic disease has never been observed in breeding colonies or primate research laboratories, most notably among hundreds of animals over several decades of study at the National Institutes of Health25, and in nearly twenty older animals continuously housed in our own facility.***
Even if the prevailing view is that sporadic CJD is due to the spontaneous formation of CJD prions, it remains possible that its apparent sporadic nature may, at least in part, result from our limited capacity to identify an environmental origin.
https://www.nature.com/articles/srep11573
https://www.ars.usda.gov/research/publications/publication/?seqNo115=361032
O.05: Transmission of prions to primates after extended silent incubation periods: Implications for BSE and scrapie risk assessment in human populations
*** We recently observed the direct transmission of a natural classical scrapie isolate to macaque after a 10-year silent incubation period,
***with features similar to some reported for human cases of sporadic CJD, albeit requiring fourfold long incubation than BSE. Scrapie, as recently evoked in humanized mice (Cassard, 2014),
***is the third potentially zoonotic PD (with BSE and L-type BSE),
***thus questioning the origin of human sporadic cases.
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PRION 2015 CONFERENCE
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5019500/
PRION 2016 TOKYO
Saturday, April 23, 2016
SCRAPIE WS-01: Prion diseases in animals and zoonotic potential 2016
Prion. 10:S15-S21. 2016 ISSN: 1933-68961933-690X
WS-01: Prion diseases in animals and zoonotic potential
***Transmission data also revealed that several scrapie prions propagate in HuPrP-Tg mice with efficiency comparable to that of cattle BSE. While the efficiency of transmission at primary passage was low, subsequent passages resulted in a highly virulent prion disease in both Met129 and Val129 mice.
***Transmission of the different scrapie isolates in these mice leads to the emergence of prion strain phenotypes that showed similar characteristics to those displayed by MM1 or VV2 sCJD prion.
***These results demonstrate that scrapie prions have a zoonotic potential and raise new questions about the possible link between animal and human prions.
http://www.tandfonline.com/doi/abs/10.1080/19336896.2016.1163048?journalCode=kprn20
Title: Transmission of scrapie prions to primate after an extended silent incubation period)
*** In complement to the recent demonstration that humanized mice are susceptible to scrapie, we report here the first observation of direct transmission of a natural classical scrapie isolate to a macaque after a 10-year incubation period. Neuropathologic examination revealed all of the features of a prion disease: spongiform change, neuronal loss, and accumulation of PrPres throughout the CNS.
*** This observation strengthens the questioning of the harmlessness of scrapie to humans, at a time when protective measures for human and animal health are being dismantled and reduced as c-BSE is considered controlled and being eradicated.
*** Our results underscore the importance of precautionary and protective measures and the necessity for long-term experimental transmission studies to assess the zoonotic potential of other animal prion strains.
http://www.ars.usda.gov/research/publications/publications.htm?SEQ_NO_115=313160
Comparing the Distribution of Ovine Classical Scrapie and Sporadic Creutzfeldt-Jakob Disease in Italy: Spatial and Temporal Associations (2002-2014)
Ru G1 ., Pocchiari M2 ., Bertolini S. 1, Pite L.1 , Puopolo M.2 , Ladogana A.2 , Perrotta M.G.3 , Meloni D 1 . (1) National reference center for the study and research on animal encephalopathies and comparative neuropathologies (CEA). Experimental Zooprophylactic Institute of Piemonte, Liguria and Valle d'Aosta, Torino, Italy.
(2) Department of Cellular Biology and Neuroscience, Istituto Superiore di Sanità, Roma, Italy. (3) Office 3 National center for the fight and emergency against animal diseases. Ministry of Health, Roma, Italy.
Aim: This study aims to investigate potential spatial and temporal associations between Creutzfeldt-Jakob disease (CJD) in humans (2010-2014) and ovine classical scrapie (CS) (2002- 2006) in Italy, serving as a proxy for exposure.
Materials and Methods: National data from prion disease surveillance in humans (sporadic CJD) and small ruminants (CS) in Italy were utilized. A descriptive geographic analysis was conducted for each disease individually. Subsequently, an ecological study was performed to compare the occurrence of both diseases at the district and regional levels. Standardized incidence ratios (SIR), adjusted for confounders, were calculated for CJD and CS by district and region, respectively, representing the outcome and proxy of exposure. Considering a possible long incubation period of CJD, two study periods were analysed: 2010-2014 for CJD and 2002-2006 for CS. Eight alternative linear regression models were developed using SIR in humans as the dependent variable and SIR in sheep as the independent variable. These models varied in the scale of SIR data (continuous vs. categorical), geographical level (district vs. region), and the potential past exposure of sheep in specific areas to a known source of infection (via a contaminated vaccine).
Results: The analysis of data at the district level revealed no significant association. However, when considering aggregated regional data, all four models consistently indicated a statistically significant positive association, suggesting a higher incidence of the disease in humans as the regional incidence of sheep scrapie increased.
Conclusions: While the results are intriguing, it is important to acknowledge the inherent limitations of ecological studies. Nevertheless, these findings provide valuable evidence to formulate a hypothesis regarding the zoonotic potential of classical scrapie. Further investigations are necessary, employing specific designs such as analytical epidemiology studies, to test this hypothesis effectively.
Funded by: Italian Ministry of Health Grant number: Realizzazione del programma epidemiologico finalizzato a dare evidenza del potenziale zoonotico delle TSE animali diverse dalla BSE. Prot. N. 0018730-17/07/2015-DGSAFCOD_UO-P
''Nevertheless, these findings provide valuable evidence to formulate a hypothesis regarding the zoonotic potential of classical scrapie. Further investigations are necessary, employing specific designs such as analytical epidemiology studies, to test this hypothesis effectively.''
Meeting-book-final-version prion 2023 Prion 2023 Congress Organizing Committee and the NeuroPrion Association, we invite you to join us for the International Conference Prion2023 from 16-20 October 2023 in Faro, Portugal.
https://prion2023.org/wp-content/uploads/2023/10/Meeting-book-final-version2.pdf
https://web.archive.org/web/20250828201533/https://prion2023.org/wp-content/uploads/2023/10/Meeting-book-final-version2.pdf
https://www.researchgate.net/profile/Syed-Zahid-Shah/publication/378314391_Meeting-book-final-version_prion_2023/links/65d44dad28b7720cecdca95f/Meeting-book-final-version-prion-2023.pdf
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Transmission of Idiopathic human prion disease CJD MM1 to small ruminant mouse models (Tg338 and Tg501).
Enric Vidal1,2, Samanta Giler1,2, Montse Ordóñez1,2, Hasier Eraña3,4, Jorge M. Charco3,4, Guillermo Cantero1,2, Juan C. Espinosa5 , Juan M. Torres5 , Vincent Béringue6 , Martí Pumarola7 and Joaquín Castilla3,8,9
Aims: About 90% of Creutzfeldt-Jakob disease cases are classified as sporadic (sCJD), that is, occur infrequently, randomly and without a known cause. It is a fatal neurodegenerative disease with an incidence of 1-1.5 cases per million per year. Epidemiological studies have been so far unable to establish a causal relationship between sCJD and prion diseases in animals.
The zoonotic potential of sheep scrapie was demonstrated in 2014 (Cassard et al., Nature Communications) through inoculation of transgenic mice overexpressing the human prion protein with scrapie isolates. The resulting prion disease was indistinguishable from that occurring after sCJD inoculation in the same model and, while these results do not demonstrate that sCJD is caused by scrapie prions, they do show that the transmission barrier between ovine and human prions is not absolute. Our aim is to further assess this zoonotic risk.
Materials and methods: we have prepared inocula from 3 sCJD cases (MM1, MV2 and VV2) and 2 VPSPr cases (MM and MV) to verify if it is possible to recover the scrapie phenotype upon inoculation in Tg338 and Tg501 ovinized mouse models. Additionally, two different inocula gCJD (E200K) and GSS (A117V) have been also included in the bioassays as controls for classical and atypical genetic human prions, respectively.
Results: No evidence of transmission was found on a first passage in Tg338 nor Tg501 ovinized mice, but on second passage, 4/10 Tg338 mice succumbed to CJDMM1 (40% attack rate after 645 dpi) and 1/12Tg501 mice (519dpi, 10 still alive). The remaining 2nd passages are still ongoing. Conclusions: In this poster, the neuropathological features of the resulting strain are discussed.
Funded by: MINECO grant number AGL2017-88535-P and PID2021-1222010B-C22 and by Interreg POCTEFA grant number EFA148/16 (RedPRION)
''but on second passage, 4/10 Tg338 mice succumbed to CJDMM1 (40% attack rate after 645 dpi) and 1/12 Tg501 mice (519dpi, 10 still alive). The remaining 2nd passages are still ongoing. Conclusions: In this poster, the neuropathological features of the resulting strain are discussed.''
Meeting-book-final-version prion 2023 Prion 2023 Congress Organizing Committee and the NeuroPrion Association, we invite you to join us for the International Conference Prion2023 from 16-20 October 2023 in Faro, Portugal.
https://prion2023.org/wp-content/uploads/2023/10/Meeting-book-final-version2.pdf
https://web.archive.org/web/20250828201533/https://prion2023.org/wp-content/uploads/2023/10/Meeting-book-final-version2.pdf
https://www.researchgate.net/profile/Syed-Zahid-Shah/publication/378314391_Meeting-book-final-version_prion_2023/links/65d44dad28b7720cecdca95f/Meeting-book-final-version-prion-2023.pdf
1: J Infect Dis 1980 Aug;142(2):205-8
Oral transmission of kuru, Creutzfeldt-Jakob disease, and scrapie to nonhuman primates.
Gibbs CJ Jr, Amyx HL, Bacote A, Masters CL, Gajdusek DC.
Kuru and Creutzfeldt-Jakob disease of humans and scrapie disease of sheep and goats were transmitted to squirrel monkeys (Saimiri sciureus) that were exposed to the infectious agents only by their nonforced consumption of known infectious tissues. The asymptomatic incubation period in the one monkey exposed to the virus of kuru was 36 months; that in the two monkeys exposed to the virus of Creutzfeldt-Jakob disease was 23 and 27 months, respectively; and that in the two monkeys exposed to the virus of scrapie was 25 and 32 months, respectively. Careful physical examination of the buccal cavities of all of the monkeys failed to reveal signs or oral lesions. One additional monkey similarly exposed to kuru has remained asymptomatic during the 39 months that it has been under observation.
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The successful transmission of kuru, Creutzfeldt-Jakob disease, and scrapie by natural feeding to squirrel monkeys that we have reported provides further grounds for concern that scrapie-infected meat may occasionally give rise in humans to Creutzfeldt-Jakob disease.
PMID: 6997404
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6997404&dopt=Abstract
Recently the question has again been brought up as to whether scrapie is transmissible to man. This has followed reports that the disease has been transmitted to primates. One particularly lurid speculation (Gajdusek 1977) conjectures that the agents of scrapie, kuru, Creutzfeldt-Jakob disease and transmissible encephalopathy of mink are varieties of a single "virus". The U.S. Department of Agriculture concluded that it could "no longer justify or permit scrapie-blood line and scrapie-exposed sheep and goats to be processed for human or animal food at slaughter or rendering plants" (ARC 84/77)" The problem is emphasised by the finding that some strains of scrapie produce lesions identical to the once which characterise the human dementias"
Whether true or not. the hypothesis that these agents might be transmissible to man raises two considerations. First, the safety of laboratory personnel requires prompt attention. Second, action such as the "scorched meat" policy of USDA makes the solution of the acrapie problem urgent if the sheep industry is not to suffer grievously.
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76/10.12/4.6
http://web.archive.org/web/20010305223125/www.bseinquiry.gov.uk/files/yb/1976/10/12004001.pdf
Nature. 1972 Mar 10;236(5341):73-4.
Transmission of scrapie to the cynomolgus monkey (Macaca fascicularis).
Gibbs CJ Jr, Gajdusek DC.
Nature 236, 73 - 74 (10 March 1972); doi:10.1038/236073a0
Transmission of Scrapie to the Cynomolgus Monkey (Macaca fascicularis)
C. J. GIBBS jun. & D. C. GAJDUSEK
National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, Maryland
SCRAPIE has been transmitted to the cynomolgus, or crab-eating, monkey (Macaca fascicularis) with an incubation period of more than 5 yr from the time of intracerebral inoculation of scrapie-infected mouse brain. The animal developed a chronic central nervous system degeneration, with ataxia, tremor and myoclonus with associated severe scrapie-like pathology of intensive astroglial hypertrophy and proliferation, neuronal vacuolation and status spongiosus of grey matter. The strain of scrapie virus used was the eighth passage in Swiss mice (NIH) of a Compton strain of scrapie obtained as ninth intracerebral passage of the agent in goat brain, from Dr R. L. Chandler (ARC, Compton, Berkshire).
http://www.nature.com/nature/journal/v236/n5341/abs/236073a0.html
***>“The agent responsible for French iatrogenic growth hormone-linked CJD taken as a control is very different from vCJD but is similar to that found in one case of sporadic CJD and one sheep scrapie isolate.”<***
Adaptation of the bovine spongiform encephalopathy agent to primates and comparison with Creutzfeldt– Jakob disease: Implications for human health
Corinne Ida Lasmézas, Jean-Guy Fournier, Virginie Nouvel, +8, and Jean-Philippe DeslysAuthors Info & Affiliations
March 20, 2001
98 (7) 4142-4147
https://doi.org/10.1073/pnas.041490898
Abstract
There is substantial scientific evidence to support the notion that bovine spongiform encephalopathy (BSE) has contaminated human beings, causing variant Creutzfeldt–Jakob disease (vCJD). This disease has raised concerns about the possibility of an iatrogenic secondary transmission to humans, because the biological properties of the primate-adapted BSE agent are unknown. We show that (i) BSE can be transmitted from primate to primate by intravenous route in 25 months, and (ii) an iatrogenic transmission of vCJD to humans could be readily recognized pathologically, whether it occurs by the central or peripheral route. Strain typing in mice demonstrates that the BSE agent adapts to macaques in the same way as it does to humans and confirms that the BSE agent is responsible for vCJD not only in the United Kingdom but also in France. The agent responsible for French iatrogenic growth hormone-linked CJD taken as a control is very different from vCJD but is similar to that found in one case of sporadic CJD and one sheep scrapie isolate. These data will be key in identifying the origin of human cases of prion disease, including accidental vCJD transmission, and could provide bases for vCJD risk assessment.
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Discussion
One aim of this study was to determine the risk of secondary transmission to humans of vCJD, which is caused not by a primarily human strain of TSE agent but by the BSE strain having passed the species barrier to humans. This risk is tightly linked to the capacity of the BSE agent to adapt to primates and harbor enhanced virulence (i.e., induce disease after a short incubation period and provoke disease even if highly diluted) and to its pathogenicity after inoculation by the peripheral route. With respect to the latter, there are huge variations between different TSE agent strains and hosts. For example, the BSE agent is pathogenic to pigs after i.c. inoculation but not after oral administration (23). Thus, we wanted to know to what extent the BSE/vCJD agent is pathogenic to humans by the i.c. and i.v. routes. To achieve this, we used the macaque model. To monitor the evolution of the BSE agent in primates, but also to verify the identity of French vCJD, we conducted parallel transmission to C57BL/6 mice, allowing strain-typing. The experimental scheme is depicted in Fig. 1.
Characterization of the BSE Agent in Primates.
The identity of the lesion profiles obtained from the brains of the French patient with vCJD, two British patients with vCJD, and nonhuman primates infected with BSE provides experimental demonstration of the fact that the BSE agent strain has been transmitted to humans both in the U.K. and in France. Further, it lends support to the validity of the macaque model as a powerful tool for the study of vCJD. As far as the evolution of the BSE agent in primates is concerned, we observed an interesting phenomenon: at first passage of BSE in macaques and with vCJD, there was a polymorphism of the lesion profile in mice in the hippocampal region, with about half of them harboring much more severe vacuolation than the mice inoculated with cattle BSE. At second passage, the polymorphism tended to disappear, with all mice showing higher vacuolation scores in the hippocampus than cattle BSE mice. This observation suggests the appearance of a variant of the BSE agent at first passage in primates and its clonal selection during second passage in primates. The lesion profiles showed that it was still the BSE agent, but the progressive appearance of a “hippocampal signature” hallmarked the evolution toward a variant by essence more virulent to primates.
Characterization of the CJD and Scrapie Strains.
Controls were set up by transmitting one French and one U.S. scrapie isolate from ruminants as well as French sCJD and iCJD cases from humans. None of these revealed a lesion profile or transmission characteristics similar or close to those of BSE or vCJD, respectively, thus extending to the present French scrapie isolate the previous observation that the BSE agent was different from all known natural scrapie strains (4, 24).
The lesion profiles of sCJD and iCJD differed only slightly in severity of the lesions, but not in shape of the profile, revealing the identity of the causative agents. One of us reported the absence of similarity between sCJD (six cases) and U.K. scrapie (eight cases) in transmission characteristics in mice (4). Herein, we made the striking observation that the French natural scrapie strain (but not the U.S. scrapie strain) has the same lesion profile and transmission times in C57BL/6 mice as do the two human TSE strains studied. This strain “affiliation” was confirmed biochemically. There is no epidemiological evidence for a link between sheep scrapie and the occurrence of CJD in humans (25). However, such a link, if it is not a general rule, would be extremely difficult to establish because of the very low incidence of CJD as well as the existence of different isolates in humans and multiple strains in scrapie. Moreover, scrapie is transmissible to nonhuman primates (26). Thus, there is still a possibility that in some instances TSE strains infecting humans do share a common origin with scrapie, as pointed out by our findings.
Transmission of vCJD and BSE to Nonhuman Primates.
vCJD transmitted readily to the cynomolgus macaque after 2 years of incubation, which was comparable to the transmission obtained from first-passaged macaque BSE and much shorter than the interspecies transmission of BSE. Starting with 100 mg of BSE–macaque brain material, dilutions up to 4 μg still provoked disease. These data suggest that the BSE agent rapidly adapts to primates accompanied by enhanced virulence.
Examination of macaque brain inoculated with vCJD revealed a similar pathology to that with second-passage BSE. The distribution of vacuolation and gliosis, as well as the pattern of PrP deposition, including the dense, sometimes florid plaques, were similar to the human vCJD and the BSE hallmarks of the first passage (1, 2). These data show that the phenotype of BSE in primates is conserved over two passages. Moreover, they confirm that the BSE agent behaves similarly in humans and macaques, a precious finding that will prove useful in the near future for the design of pathogenesis or therapeutic studies. Because of the number of macaques examined in this study, we can now reliably state that the pathology, in particular the PrP deposition pattern provoked by BSE, is similar in older and very young animals. However, plaque deposition is greater, and mature florid plaques were more numerous, in the young, which may be correlated with a longer duration of the clinical phase observed in this animal (2). This is important with regard to the fact that vCJD has been diagnosed mainly in teenagers and young adults, which raises the concern that older patients may have been misdiagnosed because of an alternative phenotype of the disease.
One should bear in mind, however, that cynomolgus macaques are all homozygotes for methionine at codon 129 of the PrP gene. Thus, our observations may not be relevant to humans carrying one or both valine alleles; however, all patients with vCJD reported to date have been M/M at this position (27). Intravenous Transmissions to Nonhuman Primates.
Brain pathology was identical in macaques inoculated i.c. and i.v. The i.v. route proved to be very efficient for the transmission of BSE, as shown by the 2-year survival of the animals, which is only 5 months longer than that obtained after inoculating the same amount of agent i.c. As the i.v. injection of the infectious agent implies per se a delayed neuroinvasion compared with a direct inoculation in the brain, this slight lengthening of the incubation period cannot, at this stage, be interpreted as a lower efficiency of infection as regards the i.c. route. These data should be taken into account in the risk assessment of iatrogenic vCJD transmission by i.v. administration of biological products of human origin. They also constitute an incentive for a complete i.v. titration.
Conclusions
From BSE and vCJD transmissions in nonhuman primates, a number of conclusions can be drawn that are of major importance for human health: (i) human-adapted BSE appears to be a variant of the BSE agent that is more virulent for humans than cattle BSE and is efficiently transmitted by the peripheral route; (ii) the detection of vCJD in unusually young patients is probably not because of a lack of diagnosis of cases in older patients, thus raising the question of the source of human contamination with BSE early in life; and (iii) iatrogenic transmissions from patients with vCJD would be readily recognized by using the same diagnostic criteria as those applied to vCJD [clinical and pathological criteria (27) comprising neuronal loss and gliosis in the thalamus correlated with high MRI signal (28, 29)], whether such contaminations had occurred by the central or i.v. route. Primary and iatrogenic cases of vCJD could be distinguished on the basis of the patient's clinical history.
The risk assessment of biological products of human origin, notably those derived from blood, has been deeply modified by the appearance of vCJD. We confirm that the BSE agent has contaminated humans not only in the U.K. and the Republic of Ireland but also in France, and we show that its pathogenic properties for primates are being enhanced by a primary passage in humans. Considering the flow of potentially contaminated bovine-derived products between 1980 and 1996, it is obvious that further vCJD cases may occur outside the U.K. Thus, and in the light of the present study, it is necessary to sustain worldwide CJD surveillance regardless of national BSE incidence and to take all precautionary measures to avoid iatrogenic transmissions from vCJD.
https://www.pnas.org/doi/10.1073/pnas.041490898
Scrapie and CJD, Suspect Symptoms, Like Lambs To the Slaughter, a review 2022
2001
Suspect symptoms
What if you can catch old-fashioned CJD by eating meat from a sheep infected with scrapie?
28 Mar 01
Like lambs to the slaughter
31 March 2001
by Debora MacKenzie Magazine issue 2284.
FOUR years ago, Terry Singeltary watched his mother die horribly from a degenerative brain disease. Doctors told him it was Alzheimer's, but Singeltary was suspicious. The diagnosis didn't fit her violent symptoms, and he demanded an autopsy. It showed she had died of sporadic Creutzfeldt-Jakob disease.
Most doctors believe that sCJD is caused by a prion protein deforming by chance into a killer. But Singeltary thinks otherwise. He is one of a number of campaigners who say that some sCJD, like the variant CJD related to BSE, is caused by eating meat from infected animals. Their suspicions have focused on sheep carrying scrapie, a BSE-like disease that is widespread in flocks across Europe and North America.
Now scientists in France have stumbled across new evidence that adds weight to the campaigners' fears. To their complete surprise, the researchers found that one strain of scrapie causes the same brain damage in mice as sCJD.
"This means we cannot rule out that at least some sCJD may be caused by some strains of scrapie," says team member Jean-Philippe Deslys of the French Atomic Energy Commission's medical research laboratory in Fontenay-aux-Roses, south-west of Paris. Hans Kretschmar of the University of Göttingen, who coordinates CJD surveillance in Germany, is so concerned by the findings that he now wants to trawl back through past sCJD cases to see if any might have been caused by eating infected mutton or lamb.
Scrapie has been around for centuries and until now there has been no evidence that it poses a risk to human health. But if the French finding means that scrapie can cause sCJD in people, countries around the world may have overlooked a CJD crisis to rival that caused by BSE.
Deslys and colleagues were originally studying vCJD, not sCJD. They injected the brains of macaque monkeys with brain from BSE cattle, and from French and British vCJD patients. The brain damage and clinical symptoms in the monkeys were the same for all three. Mice injected with the original sets of brain tissue or with infected monkey brain also developed the same symptoms.
As a control experiment, the team also injected mice with brain tissue from people and animals with other prion diseases: a French case of sCJD; a French patient who caught sCJD from human-derived growth hormone; sheep with a French strain of scrapie; and mice carrying a prion derived from an American scrapie strain. As expected, they all affected the brain in a different way from BSE and vCJD. But while the American strain of scrapie caused different damage from sCJD, the French strain produced exactly the same pathology.
"The main evidence that scrapie does not affect humans has been epidemiology," says Moira Bruce of the neuropathogenesis unit of the Institute for Animal Health in Edinburgh, who was a member of the same team as Deslys. "You see about the same incidence of the disease everywhere, whether or not there are many sheep, and in countries such as New Zealand with no scrapie." In the only previous comparisons of sCJD and scrapie in mice, Bruce found they were dissimilar.
But there are more than 20 strains of scrapie, and six of sCJD. "You would not necessarily see a relationship between the two with epidemiology if only some strains affect only some people," says Deslys. Bruce is cautious about the mouse results, but agrees they require further investigation. Other trials of scrapie and sCJD in mice, she says, are in progress.
People can have three different genetic variations of the human prion protein, and each type of protein can fold up two different ways. Kretschmar has found that these six combinations correspond to six clinical types of sCJD: each type of normal prion produces a particular pathology when it spontaneously deforms to produce sCJD.
But if these proteins deform because of infection with a disease-causing prion, the relationship between pathology and prion type should be different, as it is in vCJD. "If we look at brain samples from sporadic CJD cases and find some that do not fit the pattern," says Kretschmar, "that could mean they were caused by infection."
There are 250 deaths per year from sCJD in the US, and a similar incidence elsewhere. Singeltary and other US activists think that some of these people died after eating contaminated meat or "nutritional" pills containing dried animal brain. Governments will have a hard time facing activists like Singeltary if it turns out that some sCJD isn't as spontaneous as doctors have insisted.
Deslys's work on macaques also provides further proof that the human disease vCJD is caused by BSE. And the experiments showed that vCJD is much more virulent to primates than BSE, even when injected into the bloodstream rather than the brain. This, says Deslys, means that there is an even bigger risk than we thought that vCJD can be passed from one patient to another through contaminated blood transfusions and surgical instruments.
https://www.newscientist.com/article/mg16922840-300-like-lambs-to-the-slaughter/
*** Grant Agreement number: 222887 ***
*** Project acronym: PRIORITY ***
*** Project title: Protecting the food chain from prions: shaping European priorities through basic and applied research Funding ***
Scheme: Large-scale integrating project Period covered: from Oct. 1, 2009 to Sept. 30, 2014
Name of the scientific representative of the project's co-ordinator1, Title and Organisation: Jesús R. Requena, Ph.D., Associate Professor, Department of medicine, University of Santiago de Compostela, Spàin. Tel: 34-881815464 Fax: 34-881815403 E-mail: jesus.requena@usc.es
Project website¡ Marcador no definido. address: www.prionpriority.eu
PRIORITY, PROJECT FINAL REPORT
*** 14) Concluding that atypical scrapie can transmit to Humans and that its strain properties change as it transmits between species ***
snip...
http://cordis.europa.eu/docs/results/222/222887/final1-priority-final-report.pdf
Atypical Scrapie
***> “The WOAH and APHIS determined that it is not a disease of trade concern.” <***
Remember That!
terry
posted by Terry S. Singeltary Sr. | 10:10 AM
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