US Report, Scrapie, CWD, Cattle, Sheep, Pigs, Cervid, Humans, Zoonotic, 2026
*** 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¡ Error! 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
see;
https://nor-98.blogspot.com/2016/09/goat-k222-prpc-polymorphic-variant-does.html
Block D: Prion epidemiology
Studies on atypical scrapie were identified as a key element of this block, given the potential risk associated to this agent. We studied the permeability of Human, bovine and porcine species barriers to atypical scrapie agent transmission. Experiments in transgenic mice expressing bovine, porcine or human PrPC suggest that this TSE agent has the intrinsic ability to propagate across these species barriers including the Human one. Upon species barrier passage the biological properties and phenotype of atypical scrapie seem to be altered. Further experiments are currently ongoing (in the framework of this project but also in other projects) in order to: (i) characterize the properties of the prion that emerged from the propagation of atypical scrapie in tg Hu; (ii) to confirm that the phenomena we observed are also true for atypical scrapie isolates other than the ones we have studied.
In parallel, studies in sheep have concluded that:
*** Atypical scrapie can be transmitted by both oral and intracerebral route in sheep with various PRP genotypes
*** Low but consistent amount of infectivity accumulates in peripheral tissue (mammary gland, lymph nodes, placenta, skeletal muscles, nerves) of sheep incubating atypical scrapie.
*** The combination of data from all our studies leads us to conclude that:
*** Atypical scrapie passage through species barriers can lead to the emergence of various prions including classical BSE (following propagation in porcine PRP transgenic mice).
*** Atypical scrapie can propagate, with a low efficacy, in human PrP expressing mice. This suggests the existence of a zoonotic potential for this TSE agent.
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We advance our main conclusions and recommendations, in particular as they might affect public policy, including a detailed elaboration of the evidence that led to them. Our main recommendations are:
a. The issue of re-introducing ruminant protein into the food-chain The opinion of the members of Priority is that sustaining an absolute feed ban for ruminant protein to ruminants is the essential requirement, especially since the impact of non-classical forms of scrapie in sheep and goats is not fully understood and cannot be fully estimated. Therefore, the consortium strongly recommends prohibiting re-introduction of processed ruminant protein into the food-chain. Arguments in support of this opinion are:
• the large (and still uncharacterized) diversity of prion agents that circulate in animal populations;
• the uncertainties related to prion epidemiology in animal populations;
• the unknown efficacy of industrial processes applied to reduce microbiological risk during processed animal protein (PAP) production on most prion agents; • the intrinsic capacity of prions to cross interspecies transmission barriers; • the lack of sensitive methodology for identifying cross contamination in food.
• the evolution of natural food chains in nature (i.e. who eats whom or what) has generated an efficient barrier preventing, to some extent, novel prion epidemies and that this naturally evolved ecology should be respected.
The consortium is also hesitant to introduce processed ruminant proteins into fish food considering the paucity of data on prion infections in fishes and sea animals including those of mammalian origin, and the risk of establishing an environmental contamination of the oceans that cannot be controlled.
b. Atypical prion agents and surveillance
Atypical prion agents (see below) will probably continue to represent the dominant form of prion diseases in the near future, particularly in Europe.
*** Atypical L-type BSE has clear zoonotic potential, as demonstrated in experimental models.
*** Similarly, there are now some data that seem to indicate that the atypical scrapie agent can cross various species barriers.
*** Moreover, the current EU policy for eradicating scrapie (genetic selection in affected flocks) is ineffective for preventing atypical scrapie.
*** The recent identification of cell-to-cell propagation and the protein-encoded strain properties of human neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease, suggest that they bear the potential to be transmissible even if not with the same efficiency as CJD. More epidemiological data from large cohorts are necessary to reach any conclusion on the impact of their transmissibility on public health. Re-evaluations of safety precautions may become necessary depending on the outcome of these studies. In that context it would appear valuable
• to develop knowledge related to the pathogenesis and inter-individual transmission of atypical prion agents in ruminants (both intra- and inter-species)
• to improve the sensitivity of detection assays that are applied in the field towards this type of agent
• to maintain a robust surveillance of both animal and human populations
c. The need for extended research on prions
Intensified searching for a molecular determinants of the species barrier is recommended, since this barrier is a key for many important policy areas - risk assessment, proportional policies, the need for screening of human products and food. In this respect, prion strain structural language also remains an important issue for public health for the foreseeable future. Understanding the structural basis for strains and the basis for adaptation of a strain to a new host will require continued fundamental research. Prions maintain a complex two-way relationship with the host cell and fundamental research is needed on mechanisms for their transmission, replication and cause of nervous system dysfunction and death.
Early detection of prion infection, ideally at preclinical stage, also remains crucial for development of effective treatment strategies in humans affected by the disease.
Position of the Priority consortium
Nearly 30 years ago, the appearance in the UK of Bovine Spongiform Encephalopathy (BSE) quickly brought the previously obscure “prion diseases” to the spotlight. The ensuing health and food crises that spread throughout Europe had devastating consequences. In the UK alone, there were more than 36,000 farms directly affected by BSE and the transmission of BSE prions to humans via the food chain has caused over 200 people in Europe to die from variant Creutzfeldt-Jakob disease (vCJD) (http://www.cjd.ed.ac.uk
Origins of prion epidemies
Classical BSE now appears to be under control, with 18 EU Member States having achieved the World Organisation for Animal Health (Office International Epizooties) „negligible risk‟ status (May 2014; http://www.oie.int/en/animal-health-in-the-world/official-disease-status/bse/list-of-bse-risk-status/), and the remaining MS assessed as „controlled‟ risk. Of note, research, including EU-funded research, has played a key role in this success: while the origin of the infection was never defined, the principle driver of the epidemic was identified as prions in Meat and Bone Meal (MBM). Tests based on prion protein-specific antibodies were developed, allowing detection of infected animals, and a better understanding of disease pathogenesis and the distribution of infectivity in edible tissues; experimental investigation of transmission barriers between different species allowed a rational estimation of risks, etc. All of this led to the implementation of rational and effective policies, such as the MBM ban to protect the animal feed chain, and the Specified Risk Material (SRM) regulations to protect the human food chain.
In spite of this progress, prions are still a threat. Epidemiological re-assessment indicates that the ∼10 year incubation period separating the peaks of the BSE and the vCJD epidemics is probably too short. In addition, results from a large number of human tonsil and appendix analyses in the UK suggest that there may be a high number of asymptomatic individuals who are positive for the disease-associated conformer prion protein PrPSc. While vCJD is the only form of human prion disease that has been consistently demonstrated to have lymphoreticular involvement, there has been no systematic investigation of lymphoid tissue in cases with other prion diseases.
The human prion problem
The clinical cases of vCJD identified to date have all shared a common PrP genotype (M129M), although one pre-clinical case was confirmed as an M129V heterozygote, and it has been mooted that perhaps only the M129M proportion of the population is susceptible. However, in the UK appendix study, PrP accumulation was described in samples representing every codon 129 genotype, raising the possibility that genotype does not confer resistance but instead modulates incubation period. Apart from the two UK studies, the lymphoid tissues of non-CJD patients have not been examined for the presence of PrPSc, so, these cases may not solely represent pre-clinical vCJD, but also other forms of prion disease.
Recent experiments in highly susceptible mouse models indicate the presence of infectivity in blood or blood components at late disease stages in sporadic CJD. The significance of this experimental finding for humans has to be explored in more detail and, at the present time, there is no evidence for the transmission of prions via blood in sporadic CJD. However a likely scenario is that all those with signs of infection or abnormal PrP accumulation in peripheral tissue could have infective blood, posing the risk for transmission via blood products, which has been clearly demonstrated in experimental models, and confirmed in several cases of vCJD in man. Altogether, these data clearly demonstrate the potential risk of a second wave of vCJD, particularly when the number people identified with lymphoid accumulation of PrPSc (16/32,411) gives a prevalence estimate in the UK of 493 per million, much higher than the number of clinical cases seen to date.
The animal prion problem
An increasing number of reports on cases of “atypical” BSE in cattle throughout the EU and beyond may lead to a new epidemic, particularly since we still do not understand all factors determining the species barrier. Ovine scrapie is another concern, because it could mask ovine BSE, presumably transmissible to humans. Scrapie is endemic and not likely to be eradicated soon, although current control measures are effective at greatly reducing disease incidence. Atypical forms, which may be spontaneous, are not affected by these control measures and these forms of disease will persist in the global animal population. The low prevalence of these disease forms makes effective surveillance very challenging. However, there is a clear risk attendant on ignoring these cases without an understanding of their possible zoonotic potential, particularly when most forms of human disease have no established aetiology. In summary, atypical cases of BSE and scrapie presently clearly outnumber classical cases in cattle and sheep in all member states.
We will highlight the state-of-the-art knowledge and point out scientific challenges and the major questions for research. Strategic objectives and priorities in Europe in the future for research that aims to control, eliminate or eradicate the threat posed by prions to our food and health are also indicated.
The Priority project has focused on 4 themes, namely the structure, function, conversion and toxicity of prions; detection of prions; mechanisms of prion transmission and spreading and epidemiology of prion diseases. This paper summarizes the opinions/positions reached within these themes at the end of the project.
http://cordis.europa.eu/docs/results/222/222887/final1-priority-final-report.pdf
see;
https://nor-98.blogspot.com/2016/09/goat-k222-prpc-polymorphic-variant-does.html
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.
snip...
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
ARS Research Project: Elucidating the Pathobiology and Transmission of Transmissible Spongiform Encephalopathies 2025
“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.”
Research Project: Elucidating the Pathobiology and Transmission of Transmissible Spongiform Encephalopathies
Location: Virus and Prion Research
2025 Annual Report
Objectives
Objective 1: Develop highly sensitive detection tools to determine the distribution of CWD and scrapie prions in natural hosts (sheep, goats, cervids) and their environment.
Objective 2: Investigate the pathobiology of CWD, scrapie prion strains, and atypical TSEs in natural hosts including potential cross species transmission events.
Objective 3: Investigate the genetics of CWD susceptibility and resistance in white-tailed deer.
Objective 4: Evaluate the presence of and determine the appropriate methodology for CWD strain determination.
snip…
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
ARS Research Elucidating the Pathobiology and Transmission of Transmissible Spongiform Encephalopathies 2025 Annual Report
https://transmissiblespongiformencephalopathy.blogspot.com/2025/12/ars-research-elucidating-pathobiology.html
Chronic Wasting Disease CWD vs Scrapie TSE Prion
Volume 30, Number 8—August 2024
Research
Scrapie Versus Chronic Wasting Disease in White-Tailed Deer
Zoe J. Lambert1, Jifeng Bian, Eric D. Cassmann, M. Heather West Greenlee, and Justin J. Greenlee
Author affiliations: Oak Ridge Institute for Science and Education, Oak Ridge, Tennessee, USA (Z.J. Lambert); US Department of Agriculture, Ames, Iowa, USA (Z.J. Lambert, J. Bian, E.D. Cassmann, J.J. Greenlee); Iowa State University, Ames (Z.J. Lambert, M.H. West Greenlee) Suggested citation for this article
Abstract
White-tailed deer are susceptible to scrapie (WTD scrapie) after oronasal inoculation with the classical scrapie agent from sheep. Deer affected by WTD scrapie are difficult to differentiate from deer infected with chronic wasting disease (CWD). To assess the transmissibility of the WTD scrapie agent and tissue phenotypes when further passaged in white-tailed deer, we oronasally inoculated wild-type white-tailed deer with WTD scrapie agent. We found that WTD scrapie and CWD agents were generally similar, although some differences were noted. The greatest differences were seen in bioassays of cervidized mice that exhibited significantly longer survival periods when inoculated with WTD scrapie agent than those inoculated with CWD agent. 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.
snip…
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
Research Project: Elucidating the Pathobiology and Transmission of Transmissible Spongiform Encephalopathies
Location: Virus and Prion Research
Title: Differentiation of scrapie from chronic wasting disease in white-tailed deer
Author item LAMBERT, ZOE - Oak Ridge Institute For Science And Education (ORISE) item Bian, Jifeng item Cassmann, Eric item WEST GREENLEE, HEATHER - Iowa State University item Greenlee, Justin
Submitted to: Emerging Infectious Diseases Publication Type: Peer Reviewed Journal Publication Acceptance Date: 6/13/2024 Publication Date: N/A Citation: N/A
Interpretive Summary: Prion diseases are a neurodegenerative disease that can spread between animals. They are caused when the normal cellular prion protein misfolds and accumulates in the host’s central nervous system. This change is irreversible and invariably causes neurological disease and death of the host. The prion disease that affects sheep, scrapie, has been recognized for hundreds of years. However, chronic wasting disease, a similar disease found in white-tailed deer (WTD), has only been recognized since the 1960s. It has long been suggested that prion disease in deer (chronic wasting disease) was caused by the prion agent from sheep (scrapie). Recently, our lab confirmed that WTD will become infected by scrapie from sheep under conditions that mimic natural exposure. The disease produced in these animals was termed WTD scrapie. This manuscript addresses the next step in disease spread: whether sick WTD can pass WTD scrapie on to other deer. We found that white-tailed deer sick with scrapie can infect other deer under conditions mimicking natural exposure. The work reported in this manuscript demonstrates that CWD is difficult to differentiate from WTD scrapie. Regardless, WTD scrapie prions accumulate in the lymphoreticular system, meaning that environmental contamination is likely through feces, saliva, and other body fluids. Controlling WTD scrapie would require precautions similar to those taken with chronic wasting disease. The presence of WTD scrapie could confound mitigation efforts for chronic wasting disease. This information will be of interest to 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.
Technical Abstract: White-tailed deer (WTD) are susceptible to the scrapie agent from sheep after oronasal inoculation, termed WTD scrapie. However, results from western blotting these brainstems and lymph nodes are difficult to differentiate from WTD infected with chronic wasting disease (CWD). In order to assess the transmissibility of WTD scrapie and tissue phenotypes upon its further passage in WTD, three wildtype WTD (QQ95/GG96) were oronasally inoculated with WTD scrapie. These WTD presented with clinical signs and were euthanized between 21 and 26 months post-inoculation. Enzyme immunoassay (IDEXX) confirmed the presence of misfolded prion protein in the central nervous and lymphoreticular systems of all WTD in the study. Immunohistochemical staining, western blotting, and conformational stabilities were generally similar between the misfolded prion protein of WTD scrapie and CWD, though some differences were noted. Specifically, intraneuronal accumulation of misfolded prion protein was present in retinal ganglion cells of a WTD with WTD scrapie, not CWD. Additionally, epitope mapping revealed that the misfolded prion protein of CWD is slightly longer than that of WTD scrapie. Strong differences were seen in bioassays of cervidized mice, which exhibit significantly longer survival periods when inoculated with WTD scrapie as compared to those inoculated with CWD. Overall, this article establishes that WTD are highly susceptible to the WTD scrapie agent. Though subtle molecular differences exist between the misfolded prion protein of WTD scrapie and CWD, the presence of WTD scrapie in the lymphoreticular system determines that suspected cases be handled consistent with current guidelines for CWD.
https://www.ars.usda.gov/research/publications/publication/?seqNo115=410511
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
Citation: Greenlee, J.J., Moore, S.J., Cassmann, E.D., Lambert, Z.J., Kokemuller, R., Smith, J.D., Kunkle, R.A., Kong, Q., West Greenlee, H.M. 2022. Characterization of classical sheep scrapie in white-tailed deer after experimental oronasal exposure. Journal of Infectious Diseases. 227(12):1386-1395. Article jiac443. https://doi.org/10.1093/infdis/jiac443.
DOI: https://doi.org/10.1093/infdis/jiac443
Interpretive Summary: Chronic Wasting Disease (CWD), a fatal neurodegenerative disease that occurs in farmed and wild cervids (deer and elk) of North America, is a transmissible spongiform encephalopathy (TSE). TSEs are caused by infectious proteins called prions that are resistant to decontamination and environmental degradation. The origin of chronic wasting disease is not known, but it has many similarities to the TSE of sheep called scrapie. It has long been hypothesized that CWD could have arisen through transmission of sheep scrapie to deer. The purpose of this study was to determine if scrapie derived from sheep could be transmitted to white-tailed deer. This study reports that the deer inoculated with sheep scrapie developed clinical signs of TSE and that the abnormal prion protein could be detected in a wide range of neural and lymphoid tissues. These results indicate that deer may be susceptible to sheep scrapie if exposed to the disease in natural or agricultural settings . In addition, several strong similarities between CWD in white-tailed deer and the experimental cases of scrapie in white-tailed deer in this report suggest that it would be difficult to identify scrapie in deer were a case to occur. This information should be considered when developing plans to reduce or eliminate TSEs or advising farmers that wish to keep their deer herds free from prion diseases.
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
ORIGIN OF CHRONIC WASTING DISEASE TSE PRION?COLORADO THE ORIGIN OF CHRONIC WASTING DISEASE CWD TSE PRION?
*** Spraker suggested an interesting explanation for the occurrence of CWD. The deer pens at the Foot Hills Campus were built some 30-40 years ago by a Dr. Bob Davis. At or abut that time, allegedly, some scrapie work was conducted at this site. When deer were introduced to the pens they occupied ground that had previously been occupied by sheep.
IN CONFIDENCE, REPORT OF AN UNCONVENTIONAL SLOW VIRUS DISEASE IN ANIMALS IN THE USA 1989
http://webarchive.nationalarchives.gov.uk/20080102193705/http://www.bseinquiry.gov.uk/files/mb/m11b/tab01.pdf
The occurrence of CWD must be viewed against the contest of the locations in which it occurred. It was an incidental and unwelcome complication of the respective wildlife research programmes. Despite its subsequent recognition as a new disease of cervids, therefore justifying direct investigation, no specific research funding was forthcoming. The USDA viewed it as a wildlife problem and consequently not their province!” page 26.
https://web.archive.org/web/20060307063531/http://www.bseinquiry.gov.uk/files/mb/m11b/tab01.pdf
***> Human CWD TSE PrP, what if?
the problem is, to date, there is NO diagnostic criteria set in stone that would confirm a case of human Cwd, like there was with nvCJD (my Mom died from confirmed hvCJD a rare strain of the infamous sporadic CJDs with new strains mounting, sporadic CJD simply means ‘unknown’, IT DOES NOT MEAN 85%+ SPORADIC CJD IS ALL SPONTANEOUS, that’s all iatrogenic CJD is sporadic CJD, until the iatrogenic event is detected, confirmed, traced back, confirmed, put I to the academic domain, and finally, if your lucky, finally published to the media, and finally the public domain.) sorry, I got off course…but let me perfectly clear here, all science to date shows, Human CWD will not look like New Variant Creutzfeldt Jakob disease nvCJD. CWD to humans will look like some variant of sporadic Creutzfeldt Jakob Disease. And here me out very clearly, and this is from the to TSE Prion Gods themselves, old correspondence from way back during my investigations early BSE nvCJD days…2002
“Dear Sir/Madam, In the Archives of Neurology you quoted (the abstract of which was attached to your email), we did not say CWD in humans will present like variant CJD.. That assumption would be wrong.”
remember that statement..see below…terry
CDC CWD TSE Prion Update 2025
KEY POINTS
Chronic wasting disease affects deer, elk and similar animals in the United States and a few other countries.
The disease hasn't been shown to infect people.
However, it might be a risk to people if they have contact with or eat meat from animals infected with CWD.
https://www.cdc.gov/chronic-wasting/about/index.html
Transmission of prion infectivity from CWD-infected macaque tissues to rodent models demonstrates the zoonotic potential of chronic wasting disease.
Further passage to cervidized mice revealed transmission with a 100% attack rate.
Our findings demonstrate that macaques, considered the best model for the zoonotic potential of prions, were infected upon CWD challenge, including the oral one.
The disease manifested as atypical in macaques and initial transgenic mouse transmissions, but with infectivity present at all times, as unveiled in the bank vole model with an unusual tissue tropism.
Epidemiologic surveillance of prion disease among cervid hunters and people likely to have consumed venison contaminated with chronic wasting disease
=====
https://intcwdsympo.files.wordpress.com/2023/06/final-agenda-with-abstracts.pdf?force_download=true
Fortuitous generation of a zoonotic cervid prion strain
Aims: Whether CWD prions can infect humans remains unclear despite the very substantial scale and long history of human exposure of CWD in many states or provinces of USA and Canada. Multiple in vitro conversion experiments and in vivo animal studies indicate that the CWD-to-human transmission barrier is not unbreakable. A major long-term public health concern on CWD zoonosis is the emergence of highly zoonotic CWD strains. We aim to address the question of whether highly zoonotic CWD strains are possible.
Materials and Methods: We inoculated several sCJD brain samples into cervidized transgenic mice (Tg12), which were intended as negative controls for bioassays of brain tissues from sCJD cases who had potentially been exposed to CWD. Some of the Tg12mice became infected and their brain tissues were further examined by Western blot as well as serial passages in humanized or cervidized mice.
Results: Passage of sCJDMM1 in transgenic mice expressing elk PrP (Tg12) resulted in a “cervidized” CJD strain that we termed CJDElkPrP. We observed 100% transmission of the original CJDElkPrP in transgenic mice expressing human PrP. We passaged CJDElkPrP two more times in the Tg12mice. We found that such second and third passage CJDElkPrP prions retained 100% transmission rate in the humanized mice, despite that the natural elk CWD isolates and CJDElkPrP share the same elk PrP sequence. In contrast, we and others found zero or poor transmission of natural elk CWD isolates in humanized mice.
Conclusions: Our data indicate that highly zoonotic cervid prion strains are not only possible but also can retain zoonotic potential after serial passages in cervids, suggesting a very significant and serious long-term risk of CWD zoonosis given that the broad and continuing spread of CWD prions will provide fertile grounds for the emergence of zoonotic CWD strains over time.
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
Transmission of cervid prions to humanized mice demonstrates the zoonotic potential of CWD
Samia Hannaoui1 · Irina Zemlyankina1 · Sheng Chun Chang1 · Maria Immaculata Arifn1 · Vincent Béringue2 · Debbie McKenzie3 · Hermann M. Schatzl1 · Sabine Gilch1
Received: 24 May 2022 / Revised: 5 August 2022 / Accepted: 7 August 2022
© The Author(s) 2022
Abstract
Prions cause infectious and fatal neurodegenerative diseases in mammals. Chronic wasting disease (CWD), a prion disease of cervids, spreads efficiently among wild and farmed animals. Potential transmission to humans of CWD is a growing concern due to its increasing prevalence. Here, we provide evidence for a zoonotic potential of CWD prions, and its probable signature using mice expressing human prion protein (PrP) as an infection model. Inoculation of these mice with deer CWD isolates resulted in atypical clinical manifestation with prion seeding activity and efficient transmissible infectivity in the brain and, remarkably, in feces, but without classical neuropathological or Western blot appearances of prion diseases. Intriguingly, the protease-resistant PrP in the brain resembled that found in a familial human prion disease and was transmissible upon second passage. Our results suggest that CWD might infect humans, although the transmission barrier is likely higher compared to zoonotic transmission of cattle prions. Notably, our data suggest a different clinical presentation, prion signature, and tissue tropism, which causes challenges for detection by current diagnostic assays. Furthermore, the presence of infectious prions in feces is concerning because if this occurs in humans, it is a source for human-to-human transmission. These findings have strong implications for public health and CWD management.
Keywords Chronic wasting disease · CWD · Zoonotic potential · Prion strains · Zoonotic prions
HIGHLIGHTS OF THIS STUDY
================================
Our results suggest that CWD might infect humans, although the transmission barrier is likely higher compared to zoonotic transmission of cattle prions. Notably, our data suggest a different clinical presentation, prion signature, and tissue tropism, which causes challenges for detection by current diagnostic assays. Furthermore, the presence of infectious prions in feces is concerning because if this occurs in humans, it is a source for human-to-human transmission. These findings have strong implications for public health and CWD management.
In this study, we evaluated the zoonotic potential of CWD using a transgenic mouse model overexpressing human M129-PrPC (tg650 [12]). We inoculated tg650mice intracerebrally with two deer CWD isolates, Wisc-1 and 116AG [22, 23, 27, 29]. We demonstrate that this transgenic line was susceptible to infection with CWD prions and displayed a distinct leading clinical sign, an atypical PrPSc signature and unusual fecal shedding of infectious prions. Importantly, these prions generated by the human PrP transgenic mice were transmissible upon passage. Our results are the first evidence of a zoonotic risk of CWD when using one of the most common CWD strains, Wisc-1/CWD1 for infection. We demonstrated in a human transgenic mouse model that the species barrier for transmission of CWD to humans is not absolute. The fact that its signature was not typical raises the questions whether CWD would manifest in humans as a subclinical infection, whether it would arise through direct or indirect transmission including an intermediate host, or a silent to uncovered human-to-human transmission, and whether current detection techniques will be suffcient to unveil its presence.
Our findings strongly suggest that CWD should be regarded as an actual public health risk. Here, we use humanized mice to show that CWD prions can cross the species barrier to humans, and remarkably, infectious prions can be excreted in feces.
Our results indicate that if CWD crosses the species-barrier to humans, it is unlikely to resemble the most common forms of human prion diseases with respect to clinical signs, tissue tropism and PrPSc signature. For instance, PrPSc in variable protease-sensitive prionopathy (VPSPr), a sporadic form of human prion disease, and in the genetic form Gerstmann-Sträussler-Scheinker syndrome (GSS) is defined by an atypical PK-resistant PrPSc fragment that is non-glycosylated and truncated at both C- and N-termini, with a molecular weight between 6 and 8 kDa [24, 44–46]. These biochemical features are unique and distinctive from PrPSc (PrP27-30) found in most other human or animal prion disease. The atypical PrPSc signature detected in brain homogenate of tg650 mice #321 (1st passage) and #3063 (2nd passage), and the 7–8 kDa fragment (Figs. 2, 4) are very similar to that of GSS, both in terms of migration profile and the N-terminal cleavage site.
CWD in humans might remain subclinical but with PrPSc deposits in the brain with an unusual morphology that does not resemble the patterns usually seen in different prion diseases (e.g., mouse #328; Fig. 3), clinical with untraceable abnormal PrP (e.g., mouse #327) but still transmissible and uncovered upon subsequent passage (e.g., mouse #3063; Fig. 4), or prions have other reservoirs than the usual ones, hence the presence of infectivity in feces (e.g., mouse #327) suggesting a potential for human-to-human transmission and a real iatrogenic risk that might be unrecognizable.
“suggesting a potential for human-to-human transmission and a real iatrogenic risk that might be unrecognizable.”
=================================
Supplementary Information The online version contains supplementary material available at
https://doi.org/10.1007/s00401-022-02482-9
snip...see full text;
https://link.springer.com/article/10.1007/s00401-022-02482-9
https://link.springer.com/content/pdf/10.1007/s00401-022-02482-9.pdf
Macaque tissues to rodent models demonstrates the zoonotic potential of chronic wasting disease.
Samia Hannaoui1,2, Ginny Cheng1,2, Wiebke Wemheuer3, Walter Schulz-Schaeffer3, Sabine Gilch1,2, Hermann Schatzl1,2 1University of Calgary, Calgary, Canada. 2Calgary Prion Research Unit, Calgary, Canada. 3Institute of Neuropathology, Medical Faculty, Saarland University, Homburg/Saar, Germany
Snip…
***> Further passage to cervidized mice revealed transmission with a 100% attack rate.
***> Our findings demonstrate that macaques, considered the best model for the zoonotic potential of prions, were infected upon CWD challenge, including the oral one.
****> The disease manifested as atypical in macaques and initial transgenic mouse transmissions, but with infectivity present at all times, as unveiled in the bank vole model with an unusual tissue tropism.
***> Epidemiologic surveillance of prion disease among cervid hunters and people likely to have consumed venison contaminated with chronic wasting disease
=====
https://intcwdsympo.files.wordpress.com/2023/06/final-agenda-with-abstracts.pdf?force_download=true
Transmission of Cervid Prions to Humanized Mice Demonstrates the Zoonotic Potential of CWD
Samia Hannaouia, Irina Zemlyankinaa, Sheng Chun Changa, Maria Immaculata Arifina, Vincent Béringueb, Debbie McKenziec, Hermann M. Schatzla, and Sabine Gilcha
Results: Here, we provide the strongest evidence supporting the zoonotic potential of CWD prions, and their possible phenotype in humans. Inoculation of mice expressing human PrPCwith deer CWD isolates (strains Wisc-1 and 116AG) resulted in atypical clinical manifestations in > 75% of the mice, with myoclonus as leading clinical sign. Most of tg650brain homogenates were positive for seeding activity in RT-QuIC. Clinical disease and presentation was transmissible to tg650mice and bank voles. Intriguingly, protease-resistant PrP in the brain of tg650 mice resembled that found in a familial human prion disease and was transmissible upon passage. Abnormal PrP aggregates upon infection with Wisc-1 were detectable in thalamus, hypothalamus, and midbrain/pons regions.
Unprecedented in human prion disease, feces of CWD-inoculated tg650 mice harbored prion seeding activity and infectious prions, as shown by inoculation of bank voles and tg650 with fecal homogenates.
Conclusions: This is the first evidence that CWD can infect humans and cause disease with a distinctive clinical presentation, signature, and tropism, which might be transmissible between humans while current diagnostic assays might fail to detect it. These findings have major implications for public health and CWD-management.
https://www.tandfonline.com/doi/full/10.1080/19336896.2022.2091286
18. Zoonotic potential of moose-derived chronic wasting disease prions after adaptation in intermediate species
Tomás Barrioa, Jean-Yves Doueta, Alvina Huora, Séverine Lugana, Naïma Arona, Hervé Cassarda, Sylvie L. Benestadb, Juan Carlos Espinosac, Juan María Torresc, Olivier Andréolettia
aUnité Mixte de Recherche de l’Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement 1225 Interactions Hôtes-Agents Pathogènes, École Nationale Vétérinaire de Toulouse, 31076 Toulouse, France; bNorwegian Veterinary Institute, P.O. Box 64, NO-1431 Ås, Norway; cCentro de Investigación en Sanidad Animal (CISA-INIA), 28130, Valdeolmos, Madrid, Spain
Aims: Chronic wasting disease (CWD) is an emerging prion disease in Europe. To date, cases have been reported in three Nordic countries and in several species, including reindeer (Rangifer tarandus), moose (Alces alces) and red deer (Cervus elaphus). Cumulating data suggest that the prion strains responsible for the European cases are distinct from those circulating in North America. The biological properties of CWD prions are still poorly documented, in particular their spillover and zoonotic capacities. In this study, we aimed at characterizing the interspecies transmission potential of Norwegian moose CWD isolates.
Materials and Methods: For that purpose, we performed experimental transmissions in a panel of transgenic models expressing the PrPC sequence of various species.
Results: On first passage, one moose isolate propagated in the ovine PrPC-expressing model (Tg338). After adaptation in this host, moose CWD prions were able to transmit in mice expressing either bovine or human PrPC with high efficacy.
Conclusions: These results suggest that CWD prions can acquire enhanced zoonotic properties following adaptation in an intermediate species.
Funding
Grant number: AAPG2020 EU-CWD, ICRAD2020 TCWDE, NRC2022 NorCWD
Acknowledgement
https://www.tandfonline.com/doi/full/10.1080/19336896.2024.2424058
“ After adaptation in this host, moose CWD prions were able to transmit in mice expressing either bovine or human PrPC with high efficacy.”
“Also, we do not claim that "no-one has ever been infected with prion disease from eating venison." Our conclusion stating that we found no strong evidence of CWD transmission to humans in the article you quoted or in any other forum is limited to the patients we investigated.”
*** now, let’s see what the authors said about this casual link, personal communications years ago, and then the latest on the zoonotic potential from CWD to humans from the TOKYO PRION 2016 CONFERENCE.
see where it is stated NO STRONG evidence. so, does this mean there IS casual evidence ????
“Our conclusion stating that we found no strong evidence of CWD transmission to humans”
Subject: CWD aka MAD DEER/ELK TO HUMANS ???
Date: September 30, 2002 at 7:06 am PST
From: "Belay, Ermias"
To: Cc: "Race, Richard (NIH)" ; ; "Belay, Ermias"
Sent: Monday, September 30, 2002 9:22 AM
Subject: RE: TO CDC AND NIH - PUB MED- 3 MORE DEATHS - CWD - YOUNG HUNTERS
Dear Sir/Madam, In the Archives of Neurology you quoted (the abstract of which was attached to your email), we did not say CWD in humans will present like variant CJD.. That assumption would be wrong. I encourage you to read the whole article and call me if you have questions or need more clarification (phone: 404-639-3091).
Also, we do not claim that "no-one has ever been infected with prion disease from eating venison." Our conclusion stating that we found no strong evidence of CWD transmission to humans in the article you quoted or in any other forum is limited to the patients we investigated.
Ermias Belay, M.D. Centers for Disease Control and Prevention
Subject: TO CDC AND NIH - PUB MED- 3 MORE DEATHS - CWD - YOUNG HUNTERS
Sunday, November 10, 2002 6:26 PM .......snip........end..............TSS
-----Original Message-----
From:
Sent: Sunday, September 29, 2002 10:15 AM
To: rr26k@nih.gov; rrace@niaid.nih.gov; ebb8@CDC.GOV
Subject: TO CDC AND NIH - PUB MED- 3 MORE DEATHS - CWD - YOUNG HUNTERS
Sunday, November 10, 2002 6:26 PM .......snip........end..............TSS
Thursday, April 03, 2008
A prion disease of cervids: Chronic wasting disease 2008 1: Vet Res. 2008 Apr 3;39(4):41 A prion disease of cervids: Chronic wasting disease Sigurdson CJ.
snip...
*** twenty-seven CJD patients who regularly consumed venison were reported to the Surveillance Center, however there have been no unusual or novel prion subtypes that might indicate the appearance of a new prion strain [7, 41].
snip... full text ;
https://www.vetres.org/articles/vetres/abs/2008/04/v08092/v08092.html
https://chronic-wasting-disease.blogspot.com/2008/04/prion-disease-of-cervids-chronic.html
“regular venison eating associated with a 9 FOLD INCREASE IN RISK OF CJD”
Subject: Re: DEER SPONGIFORM ENCEPHALOPATHY SURVEY & HOUND STUDY
Date: Fri, 18 Oct 2002 23:12:22 +0100
From: Steve Dealler Reply-To: Bovine Spongiform Encephalopathy Organization: Netscape Online member
To: BSE-L@ …
######## Bovine Spongiform Encephalopathy <BSE-L@UNI-KARLSRUHE.DE> #########
Dear Terry,
An excellent piece of review as this literature is desparately difficult to get back from Government sites. What happened with the deer was that an association between deer meat eating and sporadic CJD was found in about 1993. The evidence was not great but did not disappear after several years of asking CJD cases what they had eaten. I think that the work into deer disease largely stopped because it was not helpful to the UK industry...and no specific cases were reported.
Well, if you dont look adequately like they are in USA currenly then you wont find any!
Steve Dealler
########### http://mailhost.rz.uni-karlsruhe.de/warc/bse-l.html ############
Subject: DEER SPONGIFORM ENCEPHALOPATHY SURVEY & HOUND STUDY
From: "Terry S. Singeltary Sr." <flounder@WT.NET>
Reply To: Bovine Spongiform Encephalopathy <BSE-L@UNI-KARLSRUHE.DE>
Date: Thu, 17 Oct 2002 17:04:51 -0700
snip...
''The association between venison eating and risk of CJD shows similar pattern, with regular venison eating associated with a 9 FOLD INCREASE IN RISK OF CJD (p = 0.04).''
CREUTZFELDT JAKOB DISEASE SURVEILLANCE IN THE UNITED KINGDOM THIRD ANNUAL REPORT AUGUST 1994
snip...see full report ;
http://web.archive.org/web/20090506050043/http://www.bseinquiry.gov.uk/files/yb/1994/08/00004001.pdf
http://web.archive.org/web/20090506050007/http://www.bseinquiry.gov.uk/files/yb/1994/10/00003001.pdf
http://web.archive.org/web/20090506050244/http://www.bseinquiry.gov.uk/files/yb/1994/07/00001001.pdf
Stephen Dealler is a consultant medical microbiologist deal@airtime.co.uk BSE Inquiry Steve Dealler Management In Confidence BSE: Private Submission of Bovine Brain Dealler
snip...end
########### http://mailhost.rz.uni-karlsruhe.de/warc/bse-l.html ############
*** These results would seem to suggest that CWD does indeed have zoonotic potential, at least as judged by the compatibility of CWD prions and their human PrPC target. Furthermore, extrapolation from this simple in vitro assay suggests that if zoonotic CWD occurred, it would most likely effect those of the PRNP codon 129-MM genotype and that the PrPres type would be similar to that found in the most common subtype of sCJD (MM1).***
http://www.tandfonline.com/doi/full/10.4161/pri.28124?src=recsys
http://www.tandfonline.com/doi/pdf/10.4161/pri.28124?needAccess=true
https://wwwnc.cdc.gov/eid/article/20/1/13-0858_article
Two Hunters from the Same Lodge Afflicted with Sporadic CJD: Is Chronic Wasting Disease to Blame?
(P7-13.002) Jonathan Trout, Matthew Roberts, Michel Tabet, Eithan Kotkowski, and Sarah HornAUTHORS INFO & AFFILIATIONS April 9, 2024 issue 102 (17_supplement_1) https://doi.org/10.1212/WNL.0000000000204407
Abstract Publication History Information & Authors Metrics & Citations Share Abstract
Objective:
This study presents a cluster of Creutzfeldt-Jakob disease (CJD) cases after exposure to chronic wasting disease (CWD)-infected deer, suggestive of potential prion transmission from CWD-infected deer to humans.
Background:
CJD is a rapidly progressive central nervous system disorder caused by misfolded prion proteins. CWD, a prion disease prevalent in North American deer, has raised concerns due to its possible link to CJD. Although no conclusive evidence of cross-species prion transmission exists, vigilance for such cases is crucial for public health.
Design/Methods:
Not applicable.
Results:
In 2022, a 72-year-old man with a history of consuming meat from a CWD-infected deer population presented with rapid-onset confusion and aggression. His friend, who had also eaten venison from the same deer population, recently died of CJD, raising concerns about a potential link between CWD and human prion disease. Despite aggressive symptomatic treatment of seizures and agitation, the patient’s condition deteriorated and he died within a month of initial presentation. The diagnosis was confirmed postmortem as sporadic CJD with homozygous methionine at codon 129 (sCJDMM1). The patient’s history, including a similar case in his social group, suggests a possible novel animal-to-human transmission of CWD. Based on non-human primate and mouse models, cross-species transmission of CJD is plausible. Due to the challenge of distinguishing sCJDMM1 from CWD without detailed prion protein characterization, it is not possible to definitively rule out CWD in these cases. Although causation remains unproven, this cluster emphasizes the need for further investigation into the potential risks of consuming CWD-infected deer and its implications for public health.
Conclusions:
Clusters of sporadic CJD cases may occur in regions with CWD-confirmed deer populations, hinting at potential cross-species prion transmission. Surveillance and further research are essential to better understand this possible association.
Disclosure: Mr. Trout has nothing to disclose. Dr. Roberts has nothing to disclose. Dr. Tabet has nothing to disclose. Dr. Kotkowski has nothing to disclose. Dr. Horn has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Cala Trio. The institution of Dr. Horn has received research support from Alzheimer's Association.
https://www.neurology.org/doi/abs/10.1212/WNL.0000000000204407
TUESDAY, MAY 11, 2021
A Unique Presentation of Creutzfeldt-Jakob Disease in a Patient Consuming Deer Antler Velvet
Conclusion
We believe that our patient’s case of CJD is highly suspicious for cervid etiology given the circumstances of the case as well as the strong evidence of plausibility reported in published literature. This is the first known case of CJD in a patient who had consumed deer antler velvet. Despite the confirmed diagnosis of CJD, a causal relationship between the patient’s disease and his consumption of deer antler velvet cannot be definitively concluded.
Supplemental data including molecular tissue sample analysis and autopsy findings could yield further supporting evidence. Given this patient’s clinical resemblance to CBD and the known histological similarities of CBD with CJD, clinicians should consider both diseases in the differential diagnosis of patients with a similarly esoteric presentation. Regardless of the origin of this patient’s disease, it is clear that the potential for prion transmission from cervids to humans should be further investigated by the academic community with considerable urgency.
https://thescipub.com/pdf/ajidsp.2021.43.48.pdf
''We believe that our patient’s case of CJD is highly suspicious for cervid etiology given the circumstances of the case as well as the strong evidence of plausibility reported in published literature. This is the first known case of CJD in a patient who had consumed deer antler velvet. Despite the confirmed diagnosis of CJD, a causal relationship between the patient’s disease and his consumption of deer antler velvet cannot be definitively concluded.''
https://thescipub.com/pdf/ajidsp.2021.43.48.pdf
CREUTZFELDT JAKOB DISEASE: A Unique Presentation of Creutzfeldt-Jakob Disease in a Patient Consuming Deer Antler Velvet
i was warning England and the BSE Inquiry about just this, way back in 1998, and was ask to supply information to the BSE Inquiry. for anyone that might be interested, see;
Singeltary submission to the BSE Inquiry on CJD and Nutritional Supplements 1998
ABOUT that deer antler spray and CWD TSE PRION... I have been screaming this since my neighbors mom died from cjd, and she had been taking a supplement that contained bovine brain, bovine eyeball, and other SRMs specified risk materials, the most high risk for mad cow disease. just saying...
I made a submission to the BSE Inquiry long ago during the BSE Inquiry days, and they seemed pretty interested.
Sender: "Patricia Cantos"
To: "Terry S Singeltary Sr. (E-mail)"
Subject: Your submission to the Inquiry
Date: Fri, 3 Jul 1998 10:10:05 +0100 3 July 1998
Mr Terry S Singeltary Sr. E-Mail: Flounder at wt.netRef: E2979
Dear Mr Singeltary, Thank you for your E-mail message of the 30th of June 1998 providing the Inquiry with your further comments. Thank you for offering to provide the Inquiry with any test results on the nutritional supplements your mother was taking before she died. As requested I am sending you our general Information Pack and a copy of the Chairman's letter. Please contact me if your system cannot read the attachments. Regarding your question, the Inquiry is looking into many aspects of the scientific evidence on BSE and nvCJD.
I would refer you to the transcripts of evidence we have already heard which are found on our internet site at ;
http://www.bse.org.uk.
Could you please provide the Inquiry with a copy of the press article you refer to in your e-mail? If not an approximate date for the article so that we can locate it? In the meantime, thank you for you comments. Please do not hesitate to contact me on... snip...end...tss
everyone I tell this too gets it screwed up...MY MOTHER WAS NOT TAKING THOSE SUPPLEMENTS IPLEX (that I ever knew of). this was my neighbors mother that died exactly one year previously and to the day of sporadic CJD that was diagnosed as Alzheimer’s at first. my mother died exactly a year later from the Heidenhain Variant of Creutzfeldt Jakob Disease hvCJD, and exceedingly rare strains of the ever growing sporadic CJD’s. both cases confirmed. ...kind regards, terry
ARS RESEARCH Generation of human chronic wasting disease in transgenic mice
Publication Acceptance Date: 9/8/2021
Research Project: Pathobiology, Genetics, and Detection of Transmissible Spongiform Encephalopathies Location: Virus and Prion Research
Title: Generation of human chronic wasting disease in transgenic mice
Author item WANG, ZERUI - Case Western Reserve University (CWRU) item QIN, KEFENG - University Of Chicago item CAMACHO, MANUEL - Case Western Reserve University (CWRU) item SHEN, PINGPING - Case Western Reserve University (CWRU) item YUAN, JUE - Case Western Reserve University (CWRU) item Greenlee, Justin item CUI, LI - Jilin University item KONG, QINGZHONG - Case Western Reserve University (CWRU) item MASTRIANNI, JAMES - University Of Chicago item ZOU, WEN-QUAN - Case Western Reserve University (CWRU)
Submitted to: Acta Neuropathologica Publication Type: Peer Reviewed Journal Publication Acceptance Date: 9/8/2021 Publication Date: N/A Citation: N/A
Interpretive Summary: Prion diseases are invariably fatal neurologic diseases for which there is no known prevention or cure. Chronic wasting disease (CWD) is the prion disease of deer and elk and is present in farmed and free ranging herds throughout North America. To date there is no clear evidence that the CWD agent could be transmitted to humans. This manuscript describes the use of an in vitro technique, cell-free serial protein misfolding cyclic amplification (sPMCA), to generate a CWD prion that is infectious to transgenic mice expressing the human prion protein. This study provides the first evidence that CWD prions may be able to cause misfolding in the human prion protein. This information will impact medical experts and those involved in making policy for farmed cervids and wildlife.
Technical Abstract: Chronic wasting disease (CWD) is a cervid spongiform encephalopathy or prion disease caused by the infectious prion or PrPSc, a misfolded conformer of cellular prion protein (PrPC). It has rapidly spread in North America and also has been found in Asia and Europe. In contrast to the zoonotic mad cow disease that is the first animal prion disease found transmissible to humans, the transmissibility of CWD to humans remains uncertain although most previous studies have suggested that humans may not be susceptible to CWD. Here we report the generation of an infectious human PrPSc by seeding CWD PrPSc in normal human brain PrPC through the in vitro cell-free serial protein misfolding cyclic amplification (sPMCA). Western blotting confirms that the sPMCA-induced proteinase K-resistant PrPSc is a human form, evidenced by a PrP-specific antibody that recognizes human but not cervid PrP. Remarkably, two lines of humanized transgenic (Tg) mice expressing human PrP-129Val/Val (VV) or -129Met/Met (MM) polymorphism develop prion disease at 233 ± 6 (mean ± SE) days post-inoculation (dpi) and 552 ± 27 dpi, respectively, upon intracerebral inoculation with the sPMCA-generated PrPSc. The brain of diseased Tg mice reveals the electrophoretic profile of PrPSc similar to sporadic Creutzfeldt-Jakob disease (sCJD) MM1 or VV2 subtype but different neuropathological patterns. We believe that our study provides the first evidence that CWD PrPSc is able to convert human PrPC into PrPSc in vitro and the CWD-derived human PrPSc mimics atypical sCJD subtypes in humanized Tg mice.
https://www.ars.usda.gov/research/publications/publication/?seqNo115=382551
''The brain of diseased Tg mice reveals the electrophoretic profile of PrPSc similar to sporadic Creutzfeldt-Jakob disease (sCJD) MM1 or VV2 subtype but different neuropathological patterns.''
''We believe that our study provides the first evidence that CWD PrPSc is able to convert human PrPC into PrPSc in vitro and the CWD-derived human PrPSc mimics atypical sCJD subtypes in humanized Tg mice.''
Published: 26 September 2021
Generation of human chronic wasting disease in transgenic mice
Zerui Wang, Kefeng Qin, Manuel V. Camacho, Ignazio Cali, Jue Yuan, Pingping Shen, Justin Greenlee, Qingzhong Kong, James A. Mastrianni & Wen-Quan Zou
Acta Neuropathologica Communications volume 9, Article number: 158 (2021)
Abstract
Chronic wasting disease (CWD) is a cervid prion disease caused by the accumulation of an infectious misfolded conformer (PrPSc) of cellular prion protein (PrPC). It has been spreading rapidly in North America and also found in Asia and Europe. Although bovine spongiform encephalopathy (i.e. mad cow disease) is the only animal prion disease known to be zoonotic, the transmissibility of CWD to humans remains uncertain. Here we report the generation of the first CWD-derived infectious human PrPSc by elk CWD PrPSc-seeded conversion of PrPC in normal human brain homogenates using in vitro protein misfolding cyclic amplification (PMCA). Western blotting with human PrP selective antibody confirmed that the PMCA-generated protease-resistant PrPSc was derived from the human PrPC substrate. Two lines of humanized transgenic mice expressing human PrP with either Val or Met at the polymorphic codon 129 developed clinical prion disease following intracerebral inoculation with the PMCA-generated CWD-derived human PrPSc. Diseased mice exhibited distinct PrPSc patterns and neuropathological changes in the brain. Our study, using PMCA and animal bioassays, provides the first evidence that CWD PrPSc can cross the species barrier to convert human PrPC into infectious PrPSc that can produce bona fide prion disease when inoculated into humanized transgenic mice.
Snip...
It is worth noting that the annual number of sporadic CJD (sCJD) cases in the USA has increased, with the total number of suspected and confirmed sCJD cases rising from 284 in 2003 to 511 in 2017 (https://www.cdc.gov/prions/cjd/occurrence-transmission.html). The greatly enhanced CJD surveillance and an aging population in the USA certainly contributed to the observed increase in annual sCJD case numbers in recent years, but the possibility cannot be excluded that some of the increased sCJD prevalence is linked to CWD exposure.
In the present study, using serial protein misfolding cyclic amplification (sPMCA) assay we generate PrPSc by seeding CWD prions in normal human brain homogenates. Importantly, we reveal that two lines of humanized Tg mice expressing human PrP-129VV and 129MM develop prion diseases upon intracerebral inoculation of the abnormal PrP generated by sPMCA. We believe that our study provides the first opportunity to dissect the clinical, pathological and biochemical features of the CWD-derived human prion disease in two lines of humanized Tg mice expressing two major human PrP genotypes, respectively.
https://actaneurocomms.biomedcentral.com/articles/10.1186/s40478-021-01262-y
International Conference on Emerging Diseases, Outbreaks & Case Studies & 16th Annual Meeting on Influenza March 28-29, 2018 | Orlando, USA
Qingzhong Kong
Case Western Reserve University School of Medicine, USA
Zoonotic potential of chronic wasting disease prions from cervids
Chronic wasting disease (CWD) is the prion disease in cervids (mule deer, white-tailed deer, American elk, moose, and reindeer). It has become an epidemic in North America, and it has been detected in the Europe (Norway) since 2016. The widespread CWD and popular hunting and consumption of cervid meat and other products raise serious public health concerns, but questions remain on human susceptibility to CWD prions, especially on the potential difference in zoonotic potential among the various CWD prion strains. We have been working to address this critical question for well over a decade. We used CWD samples from various cervid species to inoculate transgenic mice expressing human or elk prion protein (PrP). We found infectious prions in the spleen or brain in a small fraction of CWD-inoculated transgenic mice expressing human PrP, indicating that humans are not completely resistant to CWD prions; this finding has significant ramifications on the public health impact of CWD prions. The influence of cervid PrP polymorphisms, the prion strain dependence of CWD-to-human transmission barrier, and the characterization of experimental human CWD prions will be discussed.
Speaker Biography Qingzhong Kong has completed his PhD from the University of Massachusetts at Amherst and Post-doctoral studies at Yale University. He is currently an Associate Professor of Pathology, Neurology and Regenerative Medicine. He has published over 50 original research papers in reputable journals (including Science Translational Medicine, JCI, PNAS and Cell Reports) and has been serving as an Editorial Board Member on seven scientific journals. He has multiple research interests, including public health risks of animal prions (CWD of cervids and atypical BSE of cattle), animal modeling of human prion diseases, mechanisms of prion replication and pathogenesis, etiology of sporadic Creutzfeldt-Jacob disease (CJD) in humans, normal cellular PrP in the biology and pathology of multiple brain and peripheral diseases, proteins responsible for the α-cleavage of cellular PrP, as well as gene therapy and DNA vaccination.
qxk2@case.edu
https://www.alliedacademies.org/conference-abstracts-files/zoonotic-potential-of-chronic-wasting-disease-prions-from.pdf
https://prionconference.blogspot.com/2018/02/prion-round-table-conference-2018-may.html
Prion 2018 Conference
http://prionconference.blogspot.com/
Prion Conference 2018 Abstracts
P190 Human prion disease mortality rates by occurrence of chronic wasting disease in free ranging cervids, United States
Abrams JY (1), Maddox RA (1), Schonberger LB (1), Person MK (1), Appleby BS (2), Belay ED (1)
(1) Centers for Disease Control and Prevention (CDC), National Center for Emerging and Zoonotic Infectious Diseases, Atlanta, GA, USA (2) Case Western Reserve University, National Prion Disease Pathology Surveillance Center (NPDPSC), Cleveland, OH, USA.
Background
Chronic wasting disease (CWD) is a prion disease of deer and elk that has been identified in free ranging cervids in 23 US states. While there is currently no epidemiological evidence for zoonotic transmission through the consumption of contaminated venison, studies suggest the CWD agent can cross the species barrier in experimental models designed to closely mimic humans. We compared rates of human prion disease in states with and without CWD to examine the possibility of undetermined zoonotic transmission.
Methods
Death records from the National Center for Health Statistics, case records from the National Prion Disease Pathology Surveillance Center, and additional state case reports were combined to create a database of human prion disease cases from 2003-2015. Identification of CWD in each state was determined through reports of positive CWD tests by state wildlife agencies. Age- and race-adjusted mortality rates for human prion disease, excluding cases with known etiology, were determined for four categories of states based on CWD occurrence: highly endemic (>16 counties with CWD identified in free-ranging cervids); moderately endemic (3-10 counties with CWD); low endemic (1-2 counties with CWD); and no CWD states. States were counted as having no CWD until the year CWD was first identified. Analyses stratified by age, sex, and time period were also conducted to focus on subgroups for which zoonotic transmission would be more likely to be detected: cases <55 years old, male sex, and the latter half of the study (2010-2015).
Results
Highly endemic states had a higher rate of prion disease mortality compared to non-CWD states (rate ratio [RR]: 1.12, 95% confidence interval [CI] = 1.01 - 1.23), as did low endemic states (RR: 1.15, 95% CI = 1.04 - 1.27). Moderately endemic states did not have an elevated mortality rate (RR: 1.05, 95% CI = 0.93 - 1.17). In age-stratified analyses, prion disease mortality rates among the <55 year old population were elevated for moderately endemic states (RR: 1.57, 95% CI = 1.10 – 2.24) while mortality rates were elevated among those ≥55 for highly endemic states (RR: 1.13, 95% CI = 1.02 - 1.26) and low endemic states (RR: 1.16, 95% CI = 1.04 - 1.29). In other stratified analyses, prion disease mortality rates for males were only elevated for low endemic states (RR: 1.27, 95% CI = 1.10 - 1.48), and none of the categories of CWD-endemic states had elevated mortality rates for the latter time period (2010-2015).
Conclusions
While higher prion disease mortality rates in certain categories of states with CWD in free-ranging cervids were noted, additional stratified analyses did not reveal markedly elevated rates for potentially sensitive subgroups that would be suggestive of zoonotic transmission. Unknown confounding factors or other biases may explain state-by-state differences in prion disease mortality.
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P172 Peripheral Neuropathy in Patients with Prion Disease
Wang H(1), Cohen M(1), Appleby BS(1,2)
(1) University Hospitals Cleveland Medical Center, Cleveland, Ohio (2) National Prion Disease Pathology Surveillance Center, Cleveland, Ohio.
Prion disease is a fatal progressive neurodegenerative disease due to deposition of an abnormal protease-resistant isoform of prion protein. Typical symptoms include rapidly progressive dementia, myoclonus, visual disturbance and hallucinations. Interestingly, in patients with prion disease, the abnormal protein canould also be found in the peripheral nervous system. Case reports of prion deposition in peripheral nerves have been reported. Peripheral nerve involvement is thought to be uncommon; however, little is known about the exact prevalence and features of peripheral neuropathy in patients with prion disease.
We reviewed autopsy-proven prion cases from the National Prion Disease Pathology Surveillance Center that were diagnosed between September 2016 to March 2017. We collected information regarding prion protein diagnosis, demographics, comorbidities, clinical symptoms, physical exam, neuropathology, molecular subtype, genetics lab, brain MRI, image and EMG reports. Our study included 104 patients. Thirteen (12.5%) patients had either subjective symptoms or objective signs of peripheral neuropathy. Among these 13 patients, 3 had other known potential etiologies of peripheral neuropathy such as vitamin B12 deficiency or prior chemotherapy. Among 10 patients that had no other clear etiology, 3 (30%) had familial CJD. The most common sCJD subtype was MV1-2 (30%), followed by MM1-2 (20%). The Majority of cases wasere male (60%). Half of them had exposure to wild game. The most common subjective symptoms were tingling and/or numbness of distal extremities. The most common objective finding was diminished vibratory sensation in the feet. Half of them had an EMG with the findings ranging from fasciculations to axonal polyneuropathy or demyelinating polyneuropathy.
Our study provides an overview of the pattern of peripheral neuropathy in patients with prion disease. Among patients with peripheral neuropathy symptoms or signs, majority has polyneuropathy. It is important to document the baseline frequency of peripheral neuropathy in prion diseases as these symptoms may become important when conducting surveillance for potential novel zoonotic prion diseases.
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P177 PrP plaques in methionine homozygous Creutzfeldt-Jakob disease patients as a potential marker of iatrogenic transmission
Abrams JY (1), Schonberger LB (1), Cali I (2), Cohen Y (2), Blevins JE (2), Maddox RA (1), Belay ED (1), Appleby BS (2), Cohen ML (2)
(1) Centers for Disease Control and Prevention (CDC), National Center for Emerging and Zoonotic Infectious Diseases, Atlanta, GA, USA (2) Case Western Reserve University, National Prion Disease Pathology Surveillance Center (NPDPSC), Cleveland, OH, USA.
Background
Sporadic Creutzfeldt-Jakob disease (CJD) is widely believed to originate from de novo spontaneous conversion of normal prion protein (PrP) to its pathogenic form, but concern remains that some reported sporadic CJD cases may actually be caused by disease transmission via iatrogenic processes. For cases with methionine homozygosity (CJD-MM) at codon 129 of the PRNP gene, recent research has pointed to plaque-like PrP deposition as a potential marker of iatrogenic transmission for a subset of cases. This phenotype is theorized to originate from specific iatrogenic source CJD types that comprise roughly a quarter of known CJD cases.
Methods
We reviewed scientific literature for studies which described PrP plaques among CJD patients with known epidemiological links to iatrogenic transmission (receipt of cadaveric human grown hormone or dura mater), as well as in cases of reported sporadic CJD. The presence and description of plaques, along with CJD classification type and other contextual factors, were used to summarize the current evidence regarding plaques as a potential marker of iatrogenic transmission. In addition, 523 cases of reported sporadic CJD cases in the US from January 2013 through September 2017 were assessed for presence of PrP plaques.
Results
We identified four studies describing 52 total cases of CJD-MM among either dura mater recipients or growth hormone recipients, of which 30 were identified as having PrP plaques. While sporadic cases were not generally described as having plaques, we did identify case reports which described plaques among sporadic MM2 cases as well as case reports of plaques exclusively in white matter among sporadic MM1 cases. Among the 523 reported sporadic CJD cases, 0 of 366 MM1 cases had plaques, 2 of 48 MM2 cases had kuru plaques, and 4 of 109 MM1+2 cases had either kuru plaques or both kuru and florid plaques. Medical chart review of the six reported sporadic CJD cases with plaques did not reveal clinical histories suggestive of potential iatrogenic transmission.
Conclusions
PrP plaques occur much more frequently for iatrogenic CJD-MM cases compared to sporadic CJDMM cases. Plaques may indicate iatrogenic transmission for CJD-MM cases without a type 2 Western blot fragment. The study results suggest the absence of significant misclassifications of iatrogenic CJD as sporadic. To our knowledge, this study is the first to describe grey matter kuru plaques in apparently sporadic CJD-MM patients with a type 2 Western blot fragment.
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P180 Clinico-pathological analysis of human prion diseases in a brain bank series
Ximelis T (1), Aldecoa I (1,2), Molina-Porcel L (1,3), Grau-Rivera O (4), Ferrer I (5), Nos C (6), Gelpi E (1,7), Sánchez-Valle R (1,4)
(1) Neurological Tissue Bank of the Biobanc-Hospital ClÃnic-IDIBAPS, Barcelona, Spain (2) Pathological Service of Hospital ClÃnic de Barcelona, Barcelona, Spain (3) EAIA Trastorns Cognitius, Centre Emili Mira, Parc de Salut Mar, Barcelona, Spain (4) Department of Neurology of Hospital ClÃnic de Barcelona, Barcelona, Spain (5) Institute of Neuropathology, Hospital Universitari de Bellvitge, Hospitalet de Llobregat, Barcelona (6) General subdirectorate of Surveillance and Response to Emergencies in Public Health, Department of Public Health in Catalonia, Barcelona, Spain (7) Institute of Neurology, Medical University of Vienna, Vienna, Austria.
Background and objective:
The Neurological Tissue Bank (NTB) of the Hospital Clínic-Institut d‘Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain is the reference center in Catalonia for the neuropathological study of prion diseases in the region since 2001. The aim of this study is to analyse the characteristics of the confirmed prion diseases registered at the NTB during the last 15 years.
Methods:
We reviewed retrospectively all neuropathologically confirmed cases registered during the period January 2001 to December 2016.
Results:
176 cases (54,3% female, mean age: 67,5 years and age range: 25-86 years) of neuropathological confirmed prion diseases have been studied at the NTB. 152 cases corresponded to sporadic Creutzfeldt-Jakob disease (sCJD), 10 to genetic CJD, 10 to Fatal Familial Insomnia, 2 to GerstmannSträussler-Scheinker disease, and 2 cases to variably protease-sensitive prionopathy (VPSPr). Within sCJD subtypes the MM1 subtype was the most frequent, followed by the VV2 histotype.
Clinical and neuropathological diagnoses agreed in 166 cases (94%). The clinical diagnosis was not accurate in 10 patients with definite prion disease: 1 had a clinical diagnosis of Fronto-temporal dementia (FTD), 1 Niemann-Pick‘s disease, 1 Lewy Body‘s Disease, 2 Alzheimer‘s disease, 1 Cortico-basal syndrome and 2 undetermined dementia. Among patients with VPSPr, 1 had a clinical diagnosis of Amyotrophic lateral sclerosis (ALS) and the other one with FTD.
Concomitant pathologies are frequent in older age groups, mainly AD neuropathological changes were observed in these subjects.
Discussion:
A wide spectrum of human prion diseases have been identified in the NTB being the relative frequencies and main characteristics like other published series. There is a high rate of agreement between clinical and neuropathological diagnoses with prion diseases. These findings show the importance that public health has given to prion diseases during the past 15 years. Continuous surveillance of human prion disease allows identification of new emerging phenotypes. Brain tissue samples from these donors are available to the scientific community. For more information please visit:
http://www.clinicbiobanc.org/banc-teixits-neurologics/mostres/en_index.html
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P192 Prion amplification techniques for the rapid evaluation of surface decontamination procedures
Bruyere-Ostells L (1), Mayran C (1), Belondrade M (1), Boublik Y (2), Haïk S (3), Fournier-Wirth C (1), Nicot S (1), Bougard D (1)
(1) Pathogenesis and control of chronic infections, Etablissement Français du Sang, Inserm, Université de Montpellier, Montpellier, France. (2) Centre de Recherche en Biologie cellulaire de Montpellier, CNRS, Université de Montpellier, Montpellier, France. (3) Inserm U 1127, CNRS UMR 7225, Sorbonne Universités, UPMC Université Paris 06 UMR S 1127, Institut du Cerveau et de la Moelle épinière, ICM, Paris, France.
Aims:
Transmissible Spongiform Encephalopathies (TSE) or prion diseases are a group of incurable and always fatal neurodegenerative disorders including Creutzfeldt-Jakob diseases (CJD) in humans. These pathologies include sporadic (sCJD), genetic and acquired (variant CJD) forms. By the past, sCJD and vCJD were transmitted by different prion contaminated biological materials to patients resulting in more than 400 iatrogenic cases (iCJD). The atypical nature and the biochemical properties of the infectious agent, formed by abnormal prion protein or PrPTSE, make it particularly resistant to conventional decontamination procedures. In addition, PrPTSE is widely distributed throughout the organism before clinical onset in vCJD and can also be detected in some peripheral tissues in sporadic CJD. Risk of iatrogenic transmission of CJD by contaminated medical device remains thus a concern for healthcare facilities. Bioassay is the gold standard method to evaluate the efficacy of prion decontamination procedures but is time-consuming and expensive. Here, we propose to compare in vitro prion amplification techniques: Protein Misfolding Cyclic Amplification (PMCA) and Real-Time Quaking Induced Conversion (RT-QuIC) for the detection of residual prions on surface after decontamination.
Methods:
Stainless steel wires, by mimicking the surface of surgical instruments, were proposed as a carrier model of prions for inactivation studies. To determine the sensitivity of the two amplification techniques on wires (Surf-PMCA and Surf-QuIC), steel wires were therefore contaminated with serial dilutions of brain homogenates (BH) from a 263k infected hamster and from a patient with sCJD (MM1 subtype). We then compared the different standard decontamination procedures including partially and fully efficient treatments by detecting the residual seeding activity on 263K and sCJD contaminated wires. We completed our study by the evaluation of marketed reagents endorsed for prion decontamination.
Results:
The two amplification techniques can detect minute quantities of PrPTSE adsorbed onto a single wire. 8/8 wires contaminated with a 10-6 dilution of 263k BH and 1/6 with the 10-8 dilution are positive with Surf-PMCA. Similar performances were obtained with Surf-QuIC on 263K: 10/16 wires contaminated with 10-6 dilution and 1/8 wires contaminated with 10-8 dilution are positive. Regarding the human sCJD-MM1 prion, Surf-QuIC allows us to detect 16/16 wires contaminated with 10-6 dilutions and 14/16 with 10-7 . Results obtained after decontamination treatments are very similar between 263K and sCJD prions. Efficiency of marketed treatments to remove prions is lower than expected.
Conclusions:
Surf-PMCA and Surf-QuIC are very sensitive methods for the detection of prions on wires and could be applied to prion decontamination studies for rapid evaluation of new treatments. Sodium hypochlorite is the only product to efficiently remove seeding activity of both 263K and sCJD prions.
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WA2 Oral transmission of CWD into Cynomolgus macaques: signs of atypical disease, prion conversion and infectivity in macaques and bio-assayed transgenic mice
Schatzl HM (1, 2), Hannaoui S (1, 2), Cheng Y-C (1, 2), Gilch S (1, 2), Beekes M (3), SchulzSchaeffer W (4), Stahl-Hennig C (5) and Czub S (2, 6)
(1) University of Calgary, Calgary Prion Research Unit, Calgary, Canada (2) University of Calgary, Faculty of Veterinary Medicine, Calgary, Canada, (3) Robert Koch Institute, Berlin, Germany, (4) University of Homburg/Saar, Homburg, Germany, (5) German Primate Center, Goettingen, Germany, (6) Canadian Food Inspection Agency (CFIA), Lethbridge, Canada.
To date, BSE is the only example of interspecies transmission of an animal prion disease into humans. The potential zoonotic transmission of CWD is an alarming issue and was addressed by many groups using a variety of in vitro and in vivo experimental systems. Evidence from these studies indicated a substantial, if not absolute, species barrier, aligning with the absence of epidemiological evidence suggesting transmission into humans. Studies in non-human primates were not conclusive so far, with oral transmission into new-world monkeys and no transmission into old-world monkeys. Our consortium has challenged 18 Cynomolgus macaques with characterized CWD material, focusing on oral transmission with muscle tissue. Some macaques have orally received a total of 5 kg of muscle material over a period of 2 years. After 5-7years of incubation time some animals showed clinical symptoms indicative of prion disease, and prion neuropathology and PrPSc deposition were found in spinal cord and brain of euthanized animals. PrPSc in immunoblot was weakly detected in some spinal cord materials and various tissues tested positive in RT-QuIC, including lymph node and spleen homogenates. To prove prion infectivity in the macaque tissues, we have intracerebrally inoculated 2 lines of transgenic mice, expressing either elk or human PrP. At least 3 TgElk mice, receiving tissues from 2 different macaques, showed clinical signs of a progressive prion disease and brains were positive in immunoblot and RT-QuIC. Tissues (brain, spinal cord and spleen) from these and preclinical mice are currently tested using various read-outs and by second passage in mice. Transgenic mice expressing human PrP were so far negative for clear clinical prion disease (some mice >300 days p.i.). In parallel, the same macaque materials are inoculated into bank voles. Taken together, there is strong evidence of transmissibility of CWD orally into macaques and from macaque tissues into transgenic mouse models, although with an incomplete attack rate. The clinical and pathological presentation in macaques was mostly atypical, with a strong emphasis on spinal cord pathology. Our ongoing studies will show whether the transmission of CWD into macaques and passage in transgenic mice represents a form of non-adaptive prion amplification, and whether macaque-adapted prions have the potential to infect mice expressing human PrP. The notion that CWD can be transmitted orally into both new-world and old-world non-human primates asks for a careful reevaluation of the zoonotic risk of CWD.
See also poster P103
***> The notion that CWD can be transmitted orally into both new-world and old-world non-human primates asks for a careful reevaluation of the zoonotic risk of CWD.
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WA16 Monitoring Potential CWD Transmission to Humans
Belay ED
Centers for Disease Control and Prevention (CDC), National Center for Emerging and Zoonotic Infectious Diseases, Atlanta, GA, USA.
The spread of chronic wasting disease (CWD) in animals has raised concerns about increasing human exposure to the CWD agent via hunting and venison consumption, potentially facilitating CWD transmission to humans. Several studies have explored this possibility, including limited epidemiologic studies, in vitro experiments, and laboratory studies using various types of animal models. Most human exposures to the CWD agent in the United States would be expected to occur in association with deer and elk hunting in CWD-endemic areas. The Centers for Disease Control and Prevention (CDC) collaborated with state health departments in Colorado, Wisconsin, and Wyoming to identify persons at risk of CWD exposure and to monitor their vital status over time. Databases were established of persons who hunted in Colorado and Wyoming and those who reported consumption of venison from deer that later tested positive in Wisconsin. Information from the databases is periodically cross-checked with mortality data to determine the vital status and causes of death for deceased persons. Long-term follow-up of these hunters is needed to assess their risk of development of a prion disease linked to CWD exposure.
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P166 Characterization of CJD strain profiles in venison consumers and non-consumers from Alberta and Saskatchewan
Stephanie Booth (1,2), Lise Lamoureux (1), Debra Sorensen (1), Jennifer L. Myskiw (1,2), Megan Klassen (1,2), Michael Coulthart (3), Valerie Sim (4)
(1) Zoonotic Diseases and Special Pathogens, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg (2) Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg (3) Canadian CJD Surveillance System, Public Health Agency of Canada, Ottawa (4) Division of Neurology, Department of Medicine Centre for Prions and Protein Folding Diseases, University of Alberta, Edmonton.
Chronic wasting disease (CWD) is spreading rapidly through wild cervid populations in the Canadian provinces of Alberta and Saskatchewan. While this has implications for tourism and hunting, there is also concern over possible zoonotic transmission to humans who eat venison from infected deer. Whilst there is no evidence of any human cases of CWD to date, the Canadian CJD Surveillance System (CJDSS) in Canada is staying vigilant. When variant CJD occurred following exposure to BSE, the unique biochemical fingerprint of the pathologic PrP enabled a causal link to be confirmed. However, we cannot be sure what phenotype human CWD prions would present with, or indeed, whether this would be distinct from that see in sporadic CJD. Therefore we are undertaking a systematic analysis of the molecular diversity of CJD cases of individuals who resided in Alberta and Saskatchewan at their time of death comparing venison consumers and non-consumers, using a variety of clinical, imaging, pathological and biochemical markers. Our initial objective is to develop novel biochemical methodologies that will extend the baseline glycoform and genetic polymorphism typing that is already completed by the CJDSS. Firstly, we are reviewing MRI, EEG and pathology information from over 40 cases of CJD to select clinically affected areas for further investigation. Biochemical analysis will include assessment of the levels of protease sensitive and resistant prion protein, glycoform typing using 2D gel electrophoresis, testing seeding capabilities and kinetics of aggregation by quaking-induced conversion, and determining prion oligomer size distributions with asymmetric flow field fractionation with in-line light scattering. Progress and preliminary data will be presented. Ultimately, we intend to further define the relationship between PrP structure and disease phenotype and establish a baseline for the identification of future atypical CJD cases that may arise as a result of exposure to CWD.
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Source Prion Conference 2018 Abstracts
http://transmissiblespongiformencephalopathy.blogspot.com/2018/05/prion-2018-may-22-25-2018-santiago-de.html
http://chronic-wasting-disease.blogspot.com/2018/07/oral-transmission-of-cwd-into.html
Prion 2018 Conference
http://prionconference.blogspot.com/2018/
Volume 24, Number 8—August 2018
Research Susceptibility of Human Prion Protein to Conversion by Chronic Wasting Disease Prions
Marcelo A. BarriaComments to Author , Adriana Libori, Gordon Mitchell, and Mark W. Head Author affiliations: National CJD Research and Surveillance Unit, University of Edinburgh, Edinburgh, Scotland, UK (M.A. Barria, A. Libori, M.W. Head); National and OIE Reference Laboratory for Scrapie and CWD, Canadian Food Inspection Agency, Ottawa, Ontario, Canada (G. Mitchell)
Abstract Chronic wasting disease (CWD) is a contagious and fatal neurodegenerative disease and a serious animal health issue for deer and elk in North America. The identification of the first cases of CWD among free-ranging reindeer and moose in Europe brings back into focus the unresolved issue of whether CWD can be zoonotic like bovine spongiform encephalopathy. We used a cell-free seeded protein misfolding assay to determine whether CWD prions from elk, white-tailed deer, and reindeer in North America can convert the human prion protein to the disease-associated form. We found that prions can convert, but the efficiency of conversion is affected by polymorphic variation in the cervid and human prion protein genes. In view of the similarity of reindeer, elk, and white-tailed deer in North America to reindeer, red deer, and roe deer, respectively, in Europe, a more comprehensive and thorough assessment of the zoonotic potential of CWD might be warranted.
snip...
Discussion Characterization of the transmission properties of CWD and evaluation of their zoonotic potential are important for public health purposes. Given that CWD affects several members of the family Cervidae, it seems reasonable to consider whether the zoonotic potential of CWD prions could be affected by factors such as CWD strain, cervid species, geographic location, and Prnp–PRNP polymorphic variation. We have previously used an in vitro conversion assay (PMCA) to investigate the susceptibility of the human PrP to conversion to its disease-associated form by several animal prion diseases, including CWD (15,16,22). The sensitivity of our molecular model for the detection of zoonotic conversion depends on the combination of 1) the action of proteinase K to degrade the abundant human PrPC that constitutes the substrate while only N terminally truncating any human PrPres produced and 2) the presence of the 3F4 epitope on human but not cervid PrP. In effect, this degree of sensitivity means that any human PrPres formed during the PMCA reaction can be detected down to the limit of Western blot sensitivity. In contrast, if other antibodies that detect both cervid and human PrP are used, such as 6H4, then newly formed human PrPres must be detected as a measurable increase in PrPres over the amount remaining in the reaction product from the cervid seed. Although best known for the efficient amplification of prions in research and diagnostic contexts, the variation of the PMCA method employed in our study is optimized for the definitive detection of zoonotic reaction products of inherently inefficient conversion reactions conducted across species barriers. By using this system, we previously made and reported the novel observation that elk CWD prions could convert human PrPC from human brain and could also convert recombinant human PrPC expressed in transgenic mice and eukaryotic cell cultures (15).
A previous publication suggested that mule deer PrPSc was unable to convert humanized transgenic substrate in PMCA assays (23) and required a further step of in vitro conditioning in deer substrate PMCA before it was able to cross the deer–human molecular barrier (24). However, prions from other species, such as elk (15) and reindeer affected by CWD, appear to be compatible with the human protein in a single round of amplification (as shown in our study). These observations suggest that different deer species affected by CWD could present differing degrees of the olecular compatibility with the normal form of human PrP.
The contribution of the polymorphism at codon 129 of the human PrP gene has been extensively studied and is recognized as a risk factor for Creutzfeldt-Jakob disease (4). In cervids, the equivalent codon corresponds to the position 132 encoding methionine or leucine. This polymorphism in the elk gene has been shown to play an important role in CWD susceptibility (25,26). We have investigated the effect of this cervid Prnp polymorphism on the conversion of the humanized transgenic substrate according to the variation in the equivalent PRNP codon 129 polymorphism. Interestingly, only the homologs methionine homozygous seed–substrate reactions could readily convert the human PrP, whereas the heterozygous elk PrPSc was unable to do so, even though comparable amounts of PrPres were used to seed the reaction. In addition, we observed only low levels of human PrPres formation in the reactions seeded with the homozygous methionine (132 MM) and the heterozygous (132 ML) seeds incubated with the other 2 human polymorphic substrates (129 MV and 129 VV). The presence of the amino acid leucine at position 132 of the elk Prnp gene has been attributed to a lower degree of prion conversion compared with methionine on the basis of experiments in mice made transgenic for these polymorphic variants (26). Considering the differences observed for the amplification of the homozygous human methionine substrate by the 2 polymorphic elk seeds (MM and ML), reappraisal of the susceptibility of human PrPC by the full range of cervid polymorphic variants affected by CWD would be warranted.
In light of the recent identification of the first cases of CWD in Europe in a free-ranging reindeer (R. tarandus) in Norway (2), we also decided to evaluate the in vitro conversion potential of CWD in 2 experimentally infected reindeer (18). Formation of human PrPres was readily detectable after a single round of PMCA, and in all 3 humanized polymorphic substrates (MM, MV, and VV). This finding suggests that CWD prions from reindeer could be more compatible with human PrPC generally and might therefore present a greater risk for zoonosis than, for example, CWD prions from white-tailed deer. A more comprehensive comparison of CWD in the affected species, coupled with the polymorphic variations in the human and deer PRNP–Prnp genes, in vivo and in vitro, will be required before firm conclusions can be drawn. Analysis of the Prnp sequence of the CWD reindeer in Norway was reported to be identical to the specimens used in our study (2). This finding raises the possibility of a direct comparison of zoonotic potential between CWD acquired in the wild and that produced in a controlled laboratory setting. (Table).
The prion hypothesis proposes that direct molecular interaction between PrPSc and PrPC is necessary for conversion and prion replication. Accordingly, polymorphic variants of the PrP of host and agent might play a role in determining compatibility and potential zoonotic risk. In this study, we have examined the capacity of the human PrPC to support in vitro conversion by elk, white-tailed deer, and reindeer CWD PrPSc. Our data confirm that elk CWD prions can convert the human PrPC, at least in vitro, and show that the homologous PRNP polymorphisms at codon 129 and 132 in humans and cervids affect conversion efficiency. Other species affected by CWD, particularly caribou or reindeer, also seem able to convert the human PrP. It will be important to determine whether other polymorphic variants found in other CWD-affected Cervidae or perhaps other factors (17) exert similar effects on the ability to convert human PrP and thus affect their zoonotic potential.
Dr. Barria is a research scientist working at the National CJD Research and Surveillance Unit, University of Edinburgh. His research has focused on understanding the molecular basis of a group of fatal neurologic disorders called prion diseases.
Acknowledgments We thank Aru Balachandran for originally providing cervid brain tissues, Abigail Diack and Jean Manson for providing mouse brain tissue, and James Ironside for his critical reading of the manuscript at an early stage.
This report is independent research commissioned and funded by the United Kingdom’s Department of Health Policy Research Programme and the Government of Scotland. The views expressed in this publication are those of the authors and not necessarily those of the Department of Health or the Government of Scotland.
Author contributions: The study was conceived and designed by M.A.B. and M.W.H. The experiments were conducted by M.A.B. and A.L. Chronic wasting disease brain specimens were provided by G.M. The manuscript was written by M.A.B. and M.W.H. All authors contributed to the editing and revision of the manuscript.
https://wwwnc.cdc.gov/eid/article/24/8/16-1888_article
https://www.ed.ac.uk/clinical-brain-sciences/news/news-jul-dec-2018/cwd-prions-human-conversion
Prion 2017 Conference Abstracts
First evidence of intracranial and peroral transmission of Chronic Wasting Disease (CWD) into Cynomolgus macaques: a work in progress
Stefanie Czub1, Walter Schulz-Schaeffer2, Christiane Stahl-Hennig3, Michael Beekes4, Hermann Schaetzl5 and Dirk Motzkus6 1 University of Calgary Faculty of Veterinary Medicine/Canadian Food Inspection Agency; 2Universitatsklinikum des Saarlandes und Medizinische Fakultat der Universitat des Saarlandes; 3 Deutsches Primaten Zentrum/Goettingen; 4 Robert-Koch-Institut Berlin; 5 University of Calgary Faculty of Veterinary Medicine; 6 presently: Boehringer Ingelheim Veterinary Research Center; previously: Deutsches Primaten Zentrum/Goettingen
This is a progress report of a project which started in 2009.
21 cynomolgus macaques were challenged with characterized CWD material from white-tailed deer (WTD) or elk by intracerebral (ic), oral, and skin exposure routes. Additional blood transfusion experiments are supposed to assess the CWD contamination risk of human blood product. Challenge materials originated from symptomatic cervids for ic, skin scarification and partially per oral routes (WTD brain). Challenge material for feeding of muscle derived from preclinical WTD and from preclinical macaques for blood transfusion experiments. We have confirmed that the CWD challenge material contained at least two different CWD agents (brain material) as well as CWD prions in muscle-associated nerves. Here we present first data on a group of animals either challenged ic with steel wires or per orally and sacrificed with incubation times ranging from 4.5 to 6.9 years at postmortem. Three animals displayed signs of mild clinical disease, including anxiety, apathy, ataxia and/or tremor. In four animals wasting was observed, two of those had confirmed diabetes. All animals have variable signs of prion neuropathology in spinal cords and brains and by supersensitive IHC, reaction was detected in spinal cord segments of all animals. Protein misfolding cyclic amplification (PMCA), real-time quaking-induced conversion (RT-QuiC) and PET-blot assays to further substantiate these findings are on the way, as well as bioassays in bank voles and transgenic mice. At present, a total of 10 animals are sacrificed and read-outs are ongoing. Preclinical incubation of the remaining macaques covers a range from 6.4 to 7.10 years. Based on the species barrier and an incubation time of > 5 years for BSE in macaques and about 10 years for scrapie in macaques, we expected an onset of clinical disease beyond 6 years post inoculation.
PRION 2017 DECIPHERING NEURODEGENERATIVE DISORDERS ABSTRACTS REFERENCE
https://aabb.confex.com/aabb/2018/mediafile/Handout/Session2756/TU1-3.pdf
8. Even though human TSE‐exposure risk through consumption of game from European cervids can be assumed to be minor, if at all existing, no final conclusion can be drawn due to the overall lack of scientific data. In particular the US data do not clearly exclude the possibility of human (sporadic or familial) TSE development due to consumption of venison. The Working Group thus recognizes a potential risk to consumers if a TSE would be present in European cervids. It might be prudent considering appropriate measures to reduce such a risk, e.g. excluding tissues such as CNS and lymphoid tissues from the human food chain, which would greatly reduce any potential risk for consumers. However, it is stressed that currently, no data regarding a risk of TSE infections from cervid products are available.
https://efsa.onlinelibrary.wiley.com/doi/full/10.2903/j.efsa.2018.5132
SATURDAY, FEBRUARY 23, 2019
Chronic Wasting Disease CWD TSE Prion and THE FEAST 2003 CDC an updated review of the science 2019
https://chronic-wasting-disease.blogspot.com/2019/02/chronic-wasting-disease-cwd-tse-prion.html
TUESDAY, NOVEMBER 04, 2014
Six-year follow-up of a point-source exposure to CWD contaminated venison in an Upstate New York community: risk behaviours and health outcomes 2005–2011 Authors, though, acknowledged the study was limited in geography and sample size and so it couldn't draw a conclusion about the risk to humans. They recommended more study. Dr. Ermias Belay was the report's principal author but he said New York and Oneida County officials are following the proper course by not launching a study. "There's really nothing to monitor presently. No one's sick," Belay said, noting the disease's incubation period in deer and elk is measured in years. "
http://chronic-wasting-disease.blogspot.com/2014/11/six-year-follow-up-of-point-source.html
Transmission Studies Mule deer transmissions of CWD were by intracerebral inoculation and compared with natural cases {the following was written but with a single line marked through it ''first passage (by this route)}....TSS resulted in a more rapidly progressive clinical disease with repeated episodes of synocopy ending in coma. One control animal became affected, it is believed through contamination of inoculum (?saline). Further CWD transmissions were carried out by Dick Marsh into ferret, mink and squirrel monkey. Transmission occurred in ALL of these species with the shortest incubation period in the ferret.
snip....
https://web.archive.org/web/20090506002237/http://www..bseinquiry.gov.uk/files/mb/m11b/tab01.pdf
2004
Jeff Swann and his Mom, cwd link... sporadic CJD?, CBC NEWS Jeff Schwan sCJD, CWD, and Professor Aguzzi on BSE and sporadic CJD
????: CBCnews
https://histodb15.usz.ch/pages/Images/videos/video-004/video-004.html
2004
April 22, 2004, 10:30 AM CDT Guests: Patrick Singh, Terry Schwan, Janet Skarbek, Bill Fielding (BEGIN VIDEOTAPE) ANNOUNCER: DEBORAH NORVILLE TONIGHT.
https://www.nbcnews.com/id/wbna4806886
1997-11-10: Panorama - The British disease
https://histodb15.usz.ch/pages/Images/videos/video-009/video-009.html
Prions in Muscles of Cervids with Chronic Wasting Disease, Norway
Volume 31, Number 2—February 2025
Research
Prions in Muscles of Cervids with Chronic Wasting Disease, Norway
Snip…
In summary, the results of our study indicate that prions are widely distributed in peripheral and edible tissues of cervids in Norway, including muscles. This finding highlights the risk of human exposure to small amounts of prions through handling and consuming infected cervids.
Appendix
https://wwwnc.cdc.gov/eid/article/31/2/24-0903-app1.pdf
https://wwwnc.cdc.gov/eid/article/31/2/24-0903_article
Volume 31, Number 2—February 2025
Dispatch
Detection of Chronic Wasting Disease Prions in Raw, Processed, and Cooked Elk Meat, Texas, USA
Snip…
Of note, our data show that exposure to high temperatures used to cook the meat increased the availability of prions for in vitro amplification. Considering the potential implications in food safety and public health, we believe that the findings described in this study warrant further research. Our results suggest that although the elk meat used in this study resisted different manipulations involved in subsequent consumption by humans, their zoonotic potential was limited. Nevertheless, even though no cases of CWD transmission to human have been reported, the potential for human infection is still unclear and continued monitoring for zoonotic potential is warranted.
https://wwwnc.cdc.gov/eid/article/31/2/24-0906_article
Detection of chronic wasting disease prions in processed meats
Results: Our results show positive prion detection in all the samples analyzed using deer and elk substrates. Surprisingly, cooked meats displayed increased seeding activities. This data suggests that CWD-prions are available to people even after meats are processed and cooked.
Conclusions: These results suggest CWD prions are accessible to humans through meats, even after processing and cooking. Considering the fact that these samples were collected from already processed specimens, the availability of CWD prions to humans is probably underestimated.
"Our results show positive prion detection in all the samples analyzed using deer and elk substrates. Surprisingly, cooked meats displayed increased seeding activities."
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
DETECTION OF CHRONIC WASTING DISEASE PRIONS IN PROCESSED MEATS.
In this study, we analyzed different processed meats derived from a pre-clinical, CWD-positive free-ranging elk. Products tested included filets, sausages, boneless steaks, burgers, ham steaks, seasoned chili meats, and spiced meats. CWD-prion presence in these products were assessed by PMCA using deer and elk substrates. Our results show positive prion detection in all products. To confirm the resilience of CWD-prions to traditional cooking methods, we grilled and boiled the meat products and evaluated them for any remnant PMCA seeding activity. Results confirmed the presence of CWD-prions in these meat products suggesting that infectious particles may still be available to people even after cooking. Our results strongly suggest ongoing human exposure to CWD-prions and raise significant concerns of zoonotic transmission through ingestion of CWD contaminated meat products.
Products tested included filets, sausages, boneless steaks, burgers, ham steaks, seasoned chili meats, and spiced meats.
CWD-prion presence in these products were assessed by PMCA using deer and elk substrates.
Our results show positive prion detection in all products.
Results confirmed the presence of CWD-prions in these meat products suggesting that infectious particles may still be available to people even after cooking.
Our results strongly suggest ongoing human exposure to CWD-prions and raise significant concerns of zoonotic transmission through ingestion of CWD contaminated meat products.
https://intcwdsympo.files.wordpress.com/2023/06/final-agenda-with-abstracts.pdf?force_download=true
So, this is what we leave our children and grandchildren?
TUESDAY, APRIL 07, 2026
APHIS USDA Captive CWD Herds Update by State March 2026
CHRONIC WASTING DISEASE CASES
Updated March 2026
https://www.aphis.usda.gov/sites/default/files/status-of-captive-herds.pdf
TUESDAY, APRIL 07, 2026
APHIS USDA Captive CWD Herds Update by State March 2026
https://chronic-wasting-disease.blogspot.com/2026/04/aphis-usda-captive-cwd-herds-update-by.html
Texas Chronic Wasting Disease CWD TSE Prion Progression 2012 to 2026, Positives to date 1282 confirmed
https://chronic-wasting-disease.blogspot.com/2026/03/texas-chronic-wasting-disease-cwd-tse.html
2026 TSE PrP
chronic wasting disease cwd, TSE, cattle, sheep, pigs, cervid, primates, humans, oh my! update 2026
USA FDA PART 589 SUBSTANCES PROHIBITED FROM USE IN ANIMAL FOOD OR FEED, CWD, Scrapie, BSE, Oh My, 2026
https://prpsc.proboards.com/thread/202/usa-fda-589-feed-broken
https://madcowfeed.blogspot.com/2026/01/usa-fda-part-589-substances-prohibited.html
Transmissible Spongiform Encephalopathy TSE
Prion Prp
Chronic Wasting Disease CWD, TSE, PrP
TSE cattle
Price of TSE Prion Poker goes up substantially, all you cattle ranchers and such, better pay close attention here...terry
"Cattle with the E211K polymorphism are susceptible to the CWD agent after oronasal exposure of 0.2 g of infectious material."
Transmission of the chronic wasting disease agent from elk to cattle after oronasal exposure
Justin Greenlee, Jifeng Bian, Zoe Lambert, Alexis Frese, and Eric Cassmann Virus and Prion Research Unit, National Animal Disease Center, USDA-ARS, Ames, IA, USA
Aims: The purpose of this study was to determine the susceptibility of cattle to chronic wasting disease agent from elk.
Materials and Methods: Initial studies were conducted in bovinized mice using inoculum derived from elk with various genotypes at codon 132 (MM, LM, LL). Based upon attack rates, inoculum (10% w/v brain homogenate) from an LM132 elk was selected for transmission studies in cattle. At approximately 2 weeks of age, one wild type steer (EE211) and one steer with the E211K polymorphism (EK211) were fed 1 mL of brain homogenate in a quart of milk replacer while another 1 mL was instilled intranasally. The cattle were examined daily for clinical signs for the duration of the experiment. One steer is still under observation at 71 months post-inoculation (mpi).
Results: Inoculum derived from MM132 elk resulted in similar attack rates and incubation periods in mice expressing wild type or K211 bovine PRNP, 35% at 531 days post inoculation (dpi) and 27% at 448 dpi, respectively. Inoculum from LM132 elk had a slightly higher attack rates in mice: 45% (693 dpi) in wild type cattle PRNP and 33% (468) in K211 mice. Inoculum from LL132 elk resulted in the highest attack rate in wild type bovinized mice (53% at 625 dpi), but no K211 mice were affected at >700 days. At approximately 70 mpi, the EK211 genotype steer developed clinical signs suggestive of prion disease, depression, low head carriage, hypersalivation, and ataxia, and was necropsied. Enzyme immunoassay (IDEXX) was positive in brainstem (OD=4.00, but non-detect in retropharyngeal lymph nodes and palatine tonsil. Immunoreactivity was largely limited to the brainstem, midbrain, and cervical spinal cord with a pattern that was primarily glia-associated.
Conclusions: Cattle with the E211K polymorphism are susceptible to the CWD agent after oronasal exposure of 0.2 g of infectious material.
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
Prion Conference 2023
Transmission of the chronic wasting disease agent from elk to cattle after oronasal exposure
Conclusions: Cattle with the E211K polymorphism are susceptible to the CWD agent after oronasal exposure of 0.2 g of infectious material.
Strain characterization of chronic wasting disease in bovine-PrP transgenic mice
Conclusions: Altogether, these results exhibit the diversity of CWD strains present in the panel of CWD isolates and the ability of at least some CWD isolates to infect bovine species. Cattle being one of the most important farming species, this ability represents a potential threat to both animal and human health, and consequently deserves further study.
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
Chronic wasting disease prions in cervids and wild pigs in North America Preliminary Outbreak Assessment DEFRA 26 January 2026
DEFRA 26 January 2026 Department for Environment, Food and Rural Affairs
Preliminary Outbreak Assessment
Chronic wasting disease prions in cervids and wild pigs in North America
26 January 2026
Disease report
Chronic wasting disease (CWD) is a fatal neurodegenerative disease of cervids, such as deer, elk, moose and reindeer. It is caused by prions – infectious proteins that cause normal cellular prion proteins to misfold (CIDRAP, 2025). The disease is widespread in captive and free-ranging cervids in North America (Figure 1). For the first time, CWD prions have also been detected in the tissues of wild pigs (Sus scrofa) caught in CWD-affected areas of the USA (Soto et al. 2025). This discovery emerged from a study designed to investigate potential interactions between wild pigs and CWD prions, as wild pigs often coexist with cervids, which can shed prions into the environment. The following assessment discusses the epidemiology of CWD in North America and the detection of CWD prions in wild pigs. It also considers the potential implications for Great Britain.
Figure 1. Distribution of CWD in cervids in North America as of 11 April 2025 (USGS, 2025).Department for Environment, Food and Rural Affairs
Situation assessment
CWD is considered one of the most important cervid diseases due to its capacity for infectious spread, high mortality rate and associated socio-economic impacts on cervid farming and hunting-related industries (Kincheloe et al., 2021, CFSPH, 2024). The disease is always fatal, with no cure or vaccine (CFSPH, 2024).
CWD was first reported among captive cervids in the USA in the 1960s (Kincheloe et al., 2021). It has since been detected in captive and or free-ranging cervids in 36 US states and 5 Canadian provinces, as well as South Korea, Norway, Finland and Sweden (Silva, 2022, USGS, 2025). While the South Korean strains are thought to have originated from North America, the European strains appear to have emerged independently (Silva, 2022).
Transmission between cervids occurs by direct contact with infected animals or indirectly, through contact with a contaminated environment, most likely via the oral route (Otero et al., 2021). The disease may also be vertically transmitted from doe to fawn (Nalls et al., 2013, Salariu et al., 2015). Environmental contamination occurs when infected animals shed infectious prions in various secretions and excretions, such as urine, faeces and saliva (Otero et al., 2021). It can also occur when infected carcasses decompose and release prions into the surrounding soil and vegetation (Miller et al., 2004). The minimum number of CWD prions required to cause infection in cervids is unknown but appears to be low (Denkers et al., 2020).
The disease is difficult to control, as infected animals can also be subclinical for months or years. During this time, they can shed CWD prions, which can remain infectious in the environment for at least 2 years (Miller et al., 2004, CFSPH, 2024). Diagnosis usually relies on post-mortem tests, which may fail to identify infected animals during the early stages of the disease (CFSPH, 2024, CIDRAP, 2025). Control efforts are further hampered by lack of evidence to inform effective CWD management and control strategies (Uehlinger et al., 2016, Mori et al., 2024).
CWD in North American cervids
CWD has been reported in a range of North American cervids, including white-tailed deer, mule deer, black-tailed deer, moose, wapiti, reindeer (captive) and red deer (captive) (EFSA BIOHAZ Panel, 2023). It was first reported in captive mule deer and black-tailed deer at research facilities in Colorado and Wyoming in the late 1960s (Otero et al., 2021). These animals were derived from wild populations. The disease was later identified in Rocky Mountain elk at these facilities and subsequently, in free-ranging populations of mule deer and elk in Wyoming and Colorado. The geographic expansion of CWD in North America is thought to reflect the commercial movement of subclinical animals and natural cervid migration (Otero et al., 2021). Epidemiological data suggest that the disease spread from the USA to Canada and then to South Korea through imports of infected cervids (Otero et al., 2021). A retrospective analysis revealed that, in 1978, a Colorado‑born mule deer at Toronto Zoo in Ontario, Canada, died of CWD (Dubé et al., 2006). In 1996, the disease was detected in captive elk in Saskatchewan (Williams and Miller, 2002).
The disease
Department for Environment, Food and Rural Affairs
has since been detected in captive cervids in Alberta and Quebec and free-ranging cervids in Alberta, British Columbia, Manitoba and Saskatchewan (USGS, 2025). The origin of the outbreak in free-ranging Canadian cervids is unknown (Otero et al., 2021).
While the spread of CWD across North America is often described as ‘rapid,’ it has been suggested that this may reflect widening disease surveillance, rather than a ‘real-time’ indication of geographic spread. CWD epidemics appear to develop relatively slowly compared with other wildlife diseases (EFSA BIOHAZ Panel, 2023). Field and modelling data from North America suggest that it may take 15 to 20 years for CWD prevalence to reach 1% in free-ranging cervid populations, although more rapid transmission may occur in captive populations. The surveillance sensitivity in North America means that the disease may have been present for 10 years or more in some areas before it was detected (Miller et al., 2000).
The prevalence of CWD in affected populations or species varies across North America. In captive herds, prevalence may reach 100% over time, while in affected free-ranging populations, reported prevalence ranges from <1% to >30%. Most clinical cases are observed in cervids 2 to 7 years old, especially males, which is believed to be due to behavioural differences rather than differences in susceptibility between sexes (EFSA BIOHAZ Panel, 2023). At least 13 different risk factors may contribute towards CWD spread in North America, such as host genetics, high deer density or inappropriate disposal of deer carcasses and slaughter by-products (EFSA BIOHAZ Panel, 2019).
Approaches towards CWD control and surveillance in captive and free-ranging deer vary widely across North America within and between jurisdictions (CIDRAP, 2025). A summary of the measures in place in each US state and Canadian province is available from the CWD Alliance (2026), a coalition of wildlife conservation agencies, dedicated to providing accurate information on CWD and supporting strategies to minimise its impact on free-ranging cervids. Wildlife agencies rely on voluntary testing of hunted deer carcasses as the main mechanism for CWD surveillance and management, usually using post-mortem ELISA or immunohistochemistry methods (CIDRAP, 2025).
In the USA, Animal and Plant Health Inspection Service (APHIS) operates the CWD Herd Certification Programme (HCP) in collaboration with state and wildlife agencies. This is a voluntary scheme which aims to provide a consistent, national approach to controlling CWD in farmed cervids and preventing interstate spread by establishing control measures such as fencing, detailed record keeping and CWD testing of all cervids over 12 months old that die for any reason. The Canadian Food Inspection Agency (CFIA) operates a similar programme, the CWD Herd Certification Programme. As of December 2025, 28 states were participating in the USA’s CWD HCP and 5 Canadian provinces and one Canadian territory were participating in the Canadian programme (USDA, 2025b, CFIA, 2025).
Control methods fall within three general categories: prevention, containment, and control and suppression. Prevention and containment aim to prevent CWDDepartment for Environment, Food and Rural Affairs introduction into areas where it has not previously been reported and to limit its geographical spread once it has been introduced, respectively. Both tend to include regulatory measures such as bans on the movement of live cervids, cervid carcasses or specified risk materials. Control and suppression aim to stabilise or reduce infection rates within a herd or population through measures such as selective or random culling (EFSA BIOHAZ Panel, 2017).
Despite control efforts, CWD has continued to spread among captive and free- ranging cervids in North America, with increasing prevalence in affected areas (Uehlinger et al., 2016, CFSPH, 2024). Eradicating CWD from North America appears infeasible due to its extent of geographic spread and epidemiological characteristics, such as environmental persistence (EFSA BIOHAZ Panel, 2017).
CWD in wild pigs in the USA
Wild pigs are an invasive population in the USA, especially in the south (Figure 2). They comprise escaped domestic swine, Eurasian wild boar and hybrids of the two (Smyser et al., 2020). Wild pigs frequently coexist with cervids in areas where CWD is endemic and may be exposed to CWD prions through rooting in contaminated soil, scavenging deer carcasses and predation on fawns. These ecological interactions provide multiple routes by which wild pigs could encounter prions from infected deer (Soto et al. 2025).
Under experimental conditions, domestic pigs can become infected with CWD by oral and intracerebral routes, suggesting that wild pigs might also be susceptible. Domestic pigs rarely develop clinical signs of CWD but accumulate prions in the lymphoid tissues in their heads and gut, suggesting that, like cervids, they could shed the prions in saliva and faeces (Moore et al., 2017).
Against this background, Soto et al. (2025) investigated potential interactions between wild pigs and CWD prions. They analysed over 300 brain and lymph node samples from 178 wild pigs living across Arkansas and Texas, USA. The animals were captured by the United States Department of Agriculture (USDA) between 2020 and 2021. None of the pigs included in the study were reported to be displaying clinical signs of disease.
Using an ultra-sensitive laboratory method (protein misfolding cyclic amplification (PMCA)), the researchers identified CWD prions in up to 37% of the lymph node samples and 15% of brain samples. The lowest detection rates were in the Texas samples (below 16%), matching the lower CWD prevalence in the state’s cervid population. These findings indicate that wild pigs are naturally exposed to CWD prions in areas where the disease is present (Soto et al., 2025).
When intracerebrally inoculated with tissues from wild pigs, a small proportion of mice expressing deer prion protein developed subclinical prion infection. No transmission was detected in mice expressing pig prion protein. This suggests that wild pig tissues only contain low levels of infectious prions and that wild pigs are relatively resistant to natural infection. However, they could still contribute to CWD transmission, influencing its epidemiology, geographic distribution and interspecies spread (Soto et al., 2025).Department for Environment, Food and Rural Affairs While their exact role and importance in CWD transmission is unclear, wild pigs have considerable home ranges in North America (1.1 to 5.32 km on average), which may increase when food is scarce. This mobility could complicate efforts to control the disease if they play a role in its transmission (Soto et al., 2025).
The USDA’s APHIS does not currently conduct active surveillance for CWD in wild pigs (USDA, 2025a).
Figure 2. Geographic distribution of wild pigs (purple) in the USA as of 27 January 2025, comprising escaped domestic pigs, Eurasian wild boar and hybrids of the two (adapted from USDA, 2026). Yellow (Texas) and green (Arkansas) circles indicate the states where CWD prions were detected in wild pig tissues.
Department for Environment, Food and Rural Affairs
Implications for Great Britain
CWD is a notifiable animal disease in Great Britain, but no cases have ever been reported (Defra and APHA, 2018, CIDRAP, 2025).
The introduction of CWD into Great Britain’s cervid population could have devastating socio-economic and animal welfare impacts, resulting in marked population declines, as seen in the USA (Miller et al., 2008). There could also be significant losses to cervid farming, hunting and rural tourism industries, as well as significant costs associated with controlling the spread of the disease. The UK venison market alone is worth an estimated £100 million (Scotland Food and Drink, 2018).
There are several discrete wild pig populations in Great Britain, including wild boar and feral pigs. The largest known population is in the Forest of Dean in Gloucestershire, with an estimated 583 wild boar as of 2025/2026, although Forestry England (2025) aims to reduce the number to 400 to protect other species, such as plants and insects. Pockets of wild boar and feral pigs exist in other parts of the country, but their exact numbers are unknown (Mathews et al., 2018). The potential impact of CWD introduction into Great Britain’s wild pig population is uncertain because their role in disease transmission remains unclear. While they appear to be relatively resistant to natural CWD infection and disease, they could potentially contribute towards the maintenance and spread of CWD in Great Britain’s cervid population (Soto et al., 2025).
To reduce the risk of CWD introduction, Great Britain suspended the import of live cervids and high-risk cervid products in June 2023, including urine hunting lures, from all countries where CWD has been reported. Fresh cervid meat, excluding offal and spinal cord, can only be imported into Great Britain from CWD-affected countries if it has tested negative for CWD using an approved diagnostic method, such as immunohistochemistry, and originates from an area where CWD has not been reported or officially suspected in the last 3 years (Defra and APHA, 2026).
The current risk of CWD prions being introduced into Great Britain’s wild pig or cervid population ranges from very low (event is very rare but cannot be excluded) to negligible (event is so rare it does not merit consideration). This is based on the risk of incursion tool, developed by Roberts et al., (2011). It is also supported by a recent Defra and APHA (2025) risk assessment. While this assessment identified a few theoretical entry pathways, such as contaminated equipment, that could not be fully assessed due to limited data, there is no definitive evidence that they have ever resulted in the introduction of CWD into a new area.
Detection of CWD prions in wild pigs in the USA is unlikely to affect Great Britain’s CWD risk level, as the USA is not approved to export live wild pigs to Great Britain (Defra, 2025). Import of infected wild pig meat or wild pig by-products from the USA could theoretically introduce CWD prions into Great Britain, but the risk of this is also very low. To date, CWD prions have only been reported in lymph node and brain tissue samples in wild pigs, at levels too low to cause disease in mouse models
Department for Environment, Food and Rural Affairs
(Soto et al., 2025). However, their presence in other tissues cannot be excluded. The USA is approved to export wild pig meat and certain wild pig by-products to Great Britain, excluding offal, minced meat and germplasm (Defra, 2025), but there appears to be limited trade in these commodities.
It is difficult to quantify the exact amount of wild pig meat exported to Great Britain, as available trade data does not always distinguish between meat of wild and domestic pigs. However, based on HMRC data, the last known export of non- domestic pig meat from the USA to Great Britain was in 2013 (4,881 kg).
Conclusion
CWD has continued to spread among captive and free-ranging cervids in North America since it was first detected in the 1960s. The finding of CWD prions in wild pigs in the USA suggests they could contribute towards transmission of the disease, influencing its epidemiology, geographic distribution and interspecies spread. However, further research is needed to confirm this. CWD has never been reported in Great Britain and the current risk of CWD prions being introduced into Great Britain’s wild pig or cervid population ranges from very low to negligible.
Readers are reminded to be vigilant for signs of CWD. Information on how to spot the disease can be found here. Suspected cases must be reported immediately to the Defra Rural Services Helpline on 03000 200 301. In Wales, call 0300 303 8268. In Scotland, contact your local Field Services Office. Failure to do so is an offence. We will continue to monitor the situation.
Authors • Lawrence Finn • Dr. Lauren Perrin • John Spiropoulos • Dr. Helen RobertsDepartment for Environment, Food and Rural Affairs
References
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https://assets.publishing.service.gov.uk/media/697a3b013c71d838df6bd413/CWD_Prions_in_Cervids_and_Wild_Pigs_in_North_America.pdf
Shedding, retention and spreading of chronic wasting disease prions in the environment
Project Number 2R01AI132695-06A1 Former Number 2R01AI132695-06 Contact PI/Project Leader MORALES, RODRIGO
Abstract Text
ABSTRACT
Chronic Wasting Disease (CWD) is a prion disease affecting natural and captive cervid populations. This disease is progressively spreading across the United States and new foci of infectivity are constantly being reported. Despite decades of research, there are still several unanswered questions concerning CWD.
Compelling evidence suggest that CWD prions enter the environment through carcasses from diseased animals or by the progressive accumulation of prions shed in excreta. Unfortunately, the role that plants, parasites, predators, and scavengers play in CWD spreading has been poorly studied. During the past funding cycle, our group made important technical and conceptual contributions in this field.
Data from our group and others (in collaboration) demonstrate that plants can bind prions into their surfaces as well as transport them from soils to leaves. This is relevant, considering that prions are shown to progressively accumulate in soils and strongly suggests plants as potential vectors for CWD transmission. Unfortunately, the previously mentioned evidence has been collected using proof-of-concept conditions, including the exposure of high titers of rodent (laboratory generated) adapted prions, and grass plants only.
We have generated preliminary data showing that carrots grown in CWD infected soil carry prions in their roots and leaves as evaluated by bioassays. In contrast, tomato plants do not share these features. The significance of these findings cannot be ignored considering the interaction of CWD prions with a human and animal edible vegetable. Considering the use of carrots roots and leaves in human and animal nutrition, and the still unknown zoonotic potential of CWD, future research involving edible plants is urgently needed.
Another relevant (published) finding from our laboratory involves the high CWD infectivity titers found in nasal bots, a common cervid parasite that develops in the nasal cavity (a hotspot of prion infectivity). These parasites are found in large quantities in CWD pre- clinical and clinical deer, and may importantly contribute to environmental CWD transmission. Our research also identified CWD prions in naturally exposed flies, ticks, and dermestid beetles. However, the prion infectivity titers in these parasites have not been evaluated.
Finally, animals other than cervids, including hunters and scavengers, are expected to be exposed to CWD prions. Interestingly, we identified CWD prions and de novo generated porcine prions in tissues from wild pigs living in areas with variable CWD epidemiology. We plan to further investigate all these events and their relevance in natural prion transmission using a complementary set of techniques, including in vitro and in vivo systems. Emphasis will be made in analyzing the strain properties and zoonotic potentials of the prion agents under investigation. For this purpose, we gathered a unique group of collaborators able to supply us with the samples and expertise required to execute this project. Outcomes from this research are expected to deliver new insights on this animal prionopathy and provide regulatory agencies with useful information to control its continuous spread.
Public Health Relevance Statement
PROJECT NARRATIVE Despite decades of research, several questions remain unanswered for the Chronic Wasting Disease (CWD) epidemic affecting several deer species in the United States. Continuing with our previous R01 project, we will explore novel factors mediating the spread of CWD prions, including different plant types, invertebrate parasites (e.g., ticks, nasal bots) and scavengers (wild boars). These potential disease vectors will be studied for their ability to transmit disease within and across species, including humans.
https://reporter.nih.gov/search/VYlhnadNtUiur19eYeRPog/project-details/11227445#description
Infectious prions in brains and muscles of domestic pigs experimentally challenged with the BSE, scrapie, and CWD agents
Authors: Francisca Bravo-Risi, Fraser Brydon, Angela Chong, Kane Spicker, Justin J. Greenlee https://orcid.org/0000-0003-2202-3054, Glenn Telling, Claudio Soto https://orcid.org/0000-0002-3412-0524, Sandra Pritzkow, Marcelo A. Barria, Rodrigo Morales
ABSTRACT
Experimental studies suggest that animal species not previously described as naturally infected by prions are susceptible to prion diseases affecting sheep, cattle, and deer. These interspecies transmissions may generate prions with unknown host ranges. Pigs are susceptible to prions from different origins, including deer chronic wasting disease (CWD), sheep scrapie, and bovine spongiform encephalopathy (BSE). Here, we studied prions in brains and muscles from pigs previously infected with these different prion sources. Specifically, we measured the total prion protein (PrP) and PK-resistant PrP by western blot. Seeding activity in these tissues was evaluated using the protein misfolding cyclic amplification (PMCA) technique. We found that BSE-infected pigs contained substantially more seeding competent prions compared with those infected with CWD and scrapie. Moreover, the zoonotic potential of porcine-BSE prions seems to be relevant, as both brains and muscles from BSE-infected pigs induced the misfolding of the human prion protein in vitro. This study helps to understand the potential fate of naturally existing prion strains in a relevant host and calls for caution considering the co-existence between feral swine and other prion-susceptible animal species.
IMPORTANCE
Prions (PrPSc) are proteinaceous, infectious pathogens responsible for prion diseases. Some livestock are highly susceptible to prion diseases. These include cattle (bovine spongiform encephalopathy, BSE), sheep and goat (scrapie), and cervids (chronic wasting disease, CWD). Unfortunately, BSE has been reported to be naturally transmitted to humans and other animal species. Domestic pigs, a relevant livestock animal, have not been reported to be naturally affected by prions; however, they are susceptible to the experimental exposure to BSE, scrapie, and CWD prions. Given the widespread consumption of porcine food products by humans, we aimed to evaluate the levels of pig-derived BSE, scrapie, and CWD prions from experimentally challenged domestic pigs in brain and meat cuts (leg, cheek meat, skirt meat, and tenderloin). We detected pig-adapted prions in the brains and some muscles of these animals. Additionally, we evaluated the in vitro compatibility between pig prions and the human prion protein (as a surrogate of zoonosis). Our results show that only pig-derived BSE prions were able to induce the misfolding of the cellular human prion protein. This data highlights the consequences of prion spillovers to other animal species and their potential availability to humans.
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In summary, our data shows the dynamic of animal prions when exposed to infectious pigs, as well as their distributions and zoonotic potentials. The data presented here may be relevant to understanding the fate of naturally existing prions in a sympatric animal species relevant for human consumption. This acquires importance considering a recent report describing the interaction between CWD and wild pigs in natural settings.
https://journals.asm.org/doi/10.1128/mbio.01800-25
Volume 31, Number 1—January 2025
Dispatch
Detection of Prions in Wild Pigs (Sus scrofa) from Areas with Reported Chronic Wasting Disease Cases, United States
Paulina Soto, Francisca Bravo-Risi, Rebeca Benavente, Tucker H. Stimming, Michael J. Bodenchuk, Patrick Whitley, Clint Turnage, Terry R. Spraker, Justin Greenlee, Glenn Telling, Jennifer Malmberg, Thomas Gidlewski, Tracy Nichols, Vienna R. Brown, and Rodrigo Morales Author affiliation: The University of Texas Health Science Center at Houston, Texas, USA (P. Soto, F. Bravo-Risi, R. Benavente, T.H. Stimming, R. Morales); Centro Integrativo de Biologia y Quimica Aplicada, Universidad Bernardo O’Higgins, Santiago, Chile (P. Soto, F. Bravo-Risi, R. Morales); US Department of Agriculture, Fort Collins, Colorado, USA (M.J. Bodenchuk, P. Whitley, C. Turnage, J. Malmberg, T. Gidlewski, T. Nichols, V.R. Brown); Colorado State University, Fort Collins, Colorado, USA (T.R. Spraker, G. Telling); US Department of Agriculture, Ames, Iowa, USA (J. Greenlee)
Abstract
Using a prion amplification assay, we identified prions in tissues from wild pigs (Sus scrofa) living in areas of the United States with variable chronic wasting disease (CWD) epidemiology. Our findings indicate that scavenging swine could play a role in disseminating CWD and could therefore influence its epidemiology, geographic distribution, and interspecies spread.
Chronic wasting disease (CWD) is a prion disease of particular concern because of its uncontrolled contagious spread among various cervid species in North America https://www.usgs.gov/media/images/distribution-chronic-wasting-disease-north-america
its recent discovery in Nordic countries (1), and its increasingly uncertain zoonotic potential (2). CWD is the only animal prion disease affecting captive as well as wild animals. Persistent shedding of prions by CWD-affected animals and resulting environmental contamination is considered a major route of transmission contributing to spread of the disease. Carcasses of CWD-affected animals represent relevant sources of prion infectivity to multiple animal species that can develop disease or act as vectors to spread infection to new locations.
Free-ranging deer are sympatric with multiple animal species, including some that act as predators, scavengers, or both. Experimental transmissions to study the potential for interspecies CWD transmissions have been attempted in raccoons, ferrets, cattle, sheep, and North American rodents (3–7). Potential interspecies CWD transmission has also been addressed using transgenic (Tg) mice expressing prion proteins (PrP) from relevant animal species (8). Although no reports of natural interspecies CWD transmissions have been documented, experimental studies strongly suggest the possibility for interspecies transmission in nature exists (3–7). Inoculation and serial passage studies reveal the potential of CWD prions to adapt to noncervid species, resulting in emergence of novel prion strains with unpredicted features (9–11).
Wild pigs (Sus scrofa), also called feral swine, are an invasive population comprising domestic swine, Eurasian wild boar, and hybrids of the 2 species (12). Wild pig populations have become established in the United States (Appendix Figure 1, panel A), enabled by their high rates of fecundity; omnivorous and opportunistic diet; and widespread, often human-mediated movement (13). Wild pigs scavenge carcasses on the landscape and have an intimate relationship with the soil because of their routine rooting and wallowing behaviors (14). CWD prions have been experimentally transmitted to domestic pigs by intracerebral and oral exposure routes (15), which is relevant because wild pigs coexist with cervids in CWD endemic areas and reportedly prey on fawns and scavenge deer carcasses. Considering the species overlap in many parts of the United States (Appendix Figure 1, panel), we studied potential interactions between wild pigs and CWD prions.
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Conclusions
In summary, results from this study showed that wild pigs are exposed to cervid prions, although the pigs seem to display some resistance to infection via natural exposure. Future studies should address the susceptibility of this invasive animal species to the multiple prion strains circulating in the environment. Nonetheless, identification of CWD prions in wild pig tissues indicated the potential for pigs to move prions across the landscape, which may, in turn, influence the epidemiology and geographic spread of CWD.
https://wwwnc.cdc.gov/eid/article/31/1/24-0401_article
Title: Disease-associated prion protein detected in lymphoid tissues from pigs challenged with the agent of chronic wasting disease
Conclusions: This study demonstrates that PrPSc accumulates in lymphoid tissues from pigs challenged intracranially or orally with the CWD agent, and can be detected as early as 4 months after challenge. CWD-infected pigs rarely develop clinical disease and if they do, they do so after a long incubation period. This raises the possibility that CWD-infected pigs could shed prions into their environment long before they develop clinical disease. Furthermore, lymphoid tissues from CWD-infected pigs could present a potential source of CWD infectivity in the animal and human food chains…
https://www.ars.usda.gov/research/publications/publication/?seqNo115=337105
Chronic wasting disease prions in cervids and wild pigs in North America Preliminary Outbreak Assessment DEFRA 26 January 2026
https://transmissiblespongiformencephalopathy.blogspot.com/2026/01/chronic-wasting-disease-prions-in.html
https://prpsc.proboards.com/thread/190/confucius-ponders-wild-pigs-scrofa
https://chronic-wasting-disease.blogspot.com/2026/01/confucius-ponders-what-about-wild-pigs.html
TSE cervid
PLoS One. 2020 Aug 20;15(8):e0237410. doi: 10.1371/journal.pone.0237410. eCollection 2020.
Very low oral exposure to prions of brain or saliva origin can transmit chronic wasting disease
Nathaniel D Denkers 1 , Clare E Hoover 2 , Kristen A Davenport 3 , Davin M Henderson 1 , Erin E McNulty 1 , Amy V Nalls 1 , Candace K Mathiason 1 , Edward A Hoover 1
PMID: 32817706 PMCID: PMC7446902 DOI: 10.1371/journal.pone.0237410
Abstract
The minimum infectious dose required to induce CWD infection in cervids remains unknown, as does whether peripherally shed prions and/or multiple low dose exposures are important factors in CWD transmission. With the goal of better understand CWD infection in nature, we studied oral exposures of deer to very low doses of CWD prions and also examined whether the frequency of exposure or prion source may influence infection and pathogenesis. We orally inoculated white-tailed deer with either single or multiple divided doses of prions of brain or saliva origin and monitored infection by serial longitudinal tissue biopsies spanning over two years. We report that oral exposure to as little as 300 nanograms (ng) of CWD-positive brain or to saliva containing seeding activity equivalent to 300 ng of CWD-positive brain, were sufficient to transmit CWD disease. This was true whether the inoculum was administered as a single bolus or divided as three weekly 100 ng exposures. However, when the 300 ng total dose was apportioned as 10, 30 ng doses delivered over 12 weeks, no infection occurred. While low-dose exposures to prions of brain or saliva origin prolonged the time from inoculation to first detection of infection, once infection was established, we observed no differences in disease pathogenesis. These studies suggest that the CWD minimum infectious dose approximates 100 to 300 ng CWD-positive brain (or saliva equivalent), and that CWD infection appears to conform more with a threshold than a cumulative dose dynamic.
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Discussion
As CWD expands across North America and Scandinavia, how this disease is transmitted so efficiently remains unclear, given the low concentrations of prions shed in secretions and excretions [13, 14]. The present studies demonstrated that a single oral exposure to as little as 300nmg of CWD-positive brain or equivalent saliva can initiate infection in 100% of exposed white-tailed deer. However, distributing this dose as 10, 30 ng exposures failed to induce infection. Overall, these results suggest that the minimum oral infectious exposure approaches 100 to 300 ng of CWD-positive brain equivalent. These dynamics also invite speculation as to whether potential infection co-factors, such as particle binding [46, 47] or compromises in mucosal integrity may influence infection susceptibility, as suggested from two studies in rodent models [48, 49].
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0237410
PRION 2023 CONTINUED;
https://prion2023.org/wp-content/uploads/2023/10/Meeting-book-final-version2.pdf
http://prionconference.blogspot.com/
Prion Conference 2018 Abstracts
P190 Human prion disease mortality rates by occurrence of chronic wasting disease in free ranging cervids, United States
Abrams JY (1), Maddox RA (1), Schonberger LB (1), Person MK (1), Appleby BS (2), Belay ED (1)
(1) Centers for Disease Control and Prevention (CDC), National Center for Emerging and Zoonotic Infectious Diseases, Atlanta, GA, USA (2) Case Western Reserve University, National Prion Disease Pathology Surveillance Center (NPDPSC), Cleveland, OH, USA.
Background
Chronic wasting disease (CWD) is a prion disease of deer and elk that has been identified in free ranging cervids in 23 US states. While there is currently no epidemiological evidence for zoonotic transmission through the consumption of contaminated venison, studies suggest the CWD agent can cross the species barrier in experimental models designed to closely mimic humans. We compared rates of human prion disease in states with and without CWD to examine the possibility of undetermined zoonotic transmission.
Methods
Death records from the National Center for Health Statistics, case records from the National Prion Disease Pathology Surveillance Center, and additional state case reports were combined to create a database of human prion disease cases from 2003-2015. Identification of CWD in each state was determined through reports of positive CWD tests by state wildlife agencies. Age- and race-adjusted mortality rates for human prion disease, excluding cases with known etiology, were determined for four categories of states based on CWD occurrence: highly endemic (>16 counties with CWD identified in free-ranging cervids); moderately endemic (3-10 counties with CWD); low endemic (1-2 counties with CWD); and no CWD states. States were counted as having no CWD until the year CWD was first identified. Analyses stratified by age, sex, and time period were also conducted to focus on subgroups for which zoonotic transmission would be more likely to be detected: cases <55 years old, male sex, and the latter half of the study (2010-2015).
Results
Highly endemic states had a higher rate of prion disease mortality compared to non-CWD states (rate ratio [RR]: 1.12, 95% confidence interval [CI] = 1.01 - 1.23), as did low endemic states (RR: 1.15, 95% CI = 1.04 - 1.27). Moderately endemic states did not have an elevated mortality rate (RR: 1.05, 95% CI = 0.93 - 1.17). In age-stratified analyses, prion disease mortality rates among the <55 year old population were elevated for moderately endemic states (RR: 1.57, 95% CI = 1.10 – 2.24) while mortality rates were elevated among those ≥55 for highly endemic states (RR: 1.13, 95% CI = 1.02 - 1.26) and low endemic states (RR: 1.16, 95% CI = 1.04 - 1.29). In other stratified analyses, prion disease mortality rates for males were only elevated for low endemic states (RR: 1.27, 95% CI = 1.10 - 1.48), and none of the categories of CWD-endemic states had elevated mortality rates for the latter time period (2010-2015).
Conclusions
While higher prion disease mortality rates in certain categories of states with CWD in free-ranging cervids were noted, additional stratified analyses did not reveal markedly elevated rates for potentially sensitive subgroups that would be suggestive of zoonotic transmission. Unknown confounding factors or other biases may explain state-by-state differences in prion disease mortality.
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P172 Peripheral Neuropathy in Patients with Prion Disease
Wang H(1), Cohen M(1), Appleby BS(1,2)
(1) University Hospitals Cleveland Medical Center, Cleveland, Ohio (2) National Prion Disease Pathology Surveillance Center, Cleveland, Ohio.
Prion disease is a fatal progressive neurodegenerative disease due to deposition of an abnormal protease-resistant isoform of prion protein. Typical symptoms include rapidly progressive dementia, myoclonus, visual disturbance and hallucinations. Interestingly, in patients with prion disease, the abnormal protein canould also be found in the peripheral nervous system. Case reports of prion deposition in peripheral nerves have been reported. Peripheral nerve involvement is thought to be uncommon; however, little is known about the exact prevalence and features of peripheral neuropathy in patients with prion disease.
We reviewed autopsy-proven prion cases from the National Prion Disease Pathology Surveillance Center that were diagnosed between September 2016 to March 2017. We collected information regarding prion protein diagnosis, demographics, comorbidities, clinical symptoms, physical exam, neuropathology, molecular subtype, genetics lab, brain MRI, image and EMG reports. Our study included 104 patients. Thirteen (12.5%) patients had either subjective symptoms or objective signs of peripheral neuropathy. Among these 13 patients, 3 had other known potential etiologies of peripheral neuropathy such as vitamin B12 deficiency or prior chemotherapy. Among 10 patients that had no other clear etiology, 3 (30%) had familial CJD. The most common sCJD subtype was MV1-2 (30%), followed by MM1-2 (20%). The Majority of cases wasere male (60%). Half of them had exposure to wild game. The most common subjective symptoms were tingling and/or numbness of distal extremities. The most common objective finding was diminished vibratory sensation in the feet. Half of them had an EMG with the findings ranging from fasciculations to axonal polyneuropathy or demyelinating polyneuropathy.
Our study provides an overview of the pattern of peripheral neuropathy in patients with prion disease. Among patients with peripheral neuropathy symptoms or signs, majority has polyneuropathy. It is important to document the baseline frequency of peripheral neuropathy in prion diseases as these symptoms may become important when conducting surveillance for potential novel zoonotic prion diseases.
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P177 PrP plaques in methionine homozygous Creutzfeldt-Jakob disease patients as a potential marker of iatrogenic transmission
Abrams JY (1), Schonberger LB (1), Cali I (2), Cohen Y (2), Blevins JE (2), Maddox RA (1), Belay ED (1), Appleby BS (2), Cohen ML (2)
(1) Centers for Disease Control and Prevention (CDC), National Center for Emerging and Zoonotic Infectious Diseases, Atlanta, GA, USA (2) Case Western Reserve University, National Prion Disease Pathology Surveillance Center (NPDPSC), Cleveland, OH, USA.
Background
Sporadic Creutzfeldt-Jakob disease (CJD) is widely believed to originate from de novo spontaneous conversion of normal prion protein (PrP) to its pathogenic form, but concern remains that some reported sporadic CJD cases may actually be caused by disease transmission via iatrogenic processes. For cases with methionine homozygosity (CJD-MM) at codon 129 of the PRNP gene, recent research has pointed to plaque-like PrP deposition as a potential marker of iatrogenic transmission for a subset of cases. This phenotype is theorized to originate from specific iatrogenic source CJD types that comprise roughly a quarter of known CJD cases.
Methods
We reviewed scientific literature for studies which described PrP plaques among CJD patients with known epidemiological links to iatrogenic transmission (receipt of cadaveric human grown hormone or dura mater), as well as in cases of reported sporadic CJD. The presence and description of plaques, along with CJD classification type and other contextual factors, were used to summarize the current evidence regarding plaques as a potential marker of iatrogenic transmission. In addition, 523 cases of reported sporadic CJD cases in the US from January 2013 through September 2017 were assessed for presence of PrP plaques.
Results
We identified four studies describing 52 total cases of CJD-MM among either dura mater recipients or growth hormone recipients, of which 30 were identified as having PrP plaques. While sporadic cases were not generally described as having plaques, we did identify case reports which described plaques among sporadic MM2 cases as well as case reports of plaques exclusively in white matter among sporadic MM1 cases. Among the 523 reported sporadic CJD cases, 0 of 366 MM1 cases had plaques, 2 of 48 MM2 cases had kuru plaques, and 4 of 109 MM1+2 cases had either kuru plaques or both kuru and florid plaques. Medical chart review of the six reported sporadic CJD cases with plaques did not reveal clinical histories suggestive of potential iatrogenic transmission.
Conclusions
PrP plaques occur much more frequently for iatrogenic CJD-MM cases compared to sporadic CJDMM cases. Plaques may indicate iatrogenic transmission for CJD-MM cases without a type 2 Western blot fragment. The study results suggest the absence of significant misclassifications of iatrogenic CJD as sporadic. To our knowledge, this study is the first to describe grey matter kuru plaques in apparently sporadic CJD-MM patients with a type 2 Western blot fragment.
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P180 Clinico-pathological analysis of human prion diseases in a brain bank series
Ximelis T (1), Aldecoa I (1,2), Molina-Porcel L (1,3), Grau-Rivera O (4), Ferrer I (5), Nos C (6), Gelpi E (1,7), Sánchez-Valle R (1,4)
(1) Neurological Tissue Bank of the Biobanc-Hospital ClÃnic-IDIBAPS, Barcelona, Spain (2) Pathological Service of Hospital ClÃnic de Barcelona, Barcelona, Spain (3) EAIA Trastorns Cognitius, Centre Emili Mira, Parc de Salut Mar, Barcelona, Spain (4) Department of Neurology of Hospital ClÃnic de Barcelona, Barcelona, Spain (5) Institute of Neuropathology, Hospital Universitari de Bellvitge, Hospitalet de Llobregat, Barcelona (6) General subdirectorate of Surveillance and Response to Emergencies in Public Health, Department of Public Health in Catalonia, Barcelona, Spain (7) Institute of Neurology, Medical University of Vienna, Vienna, Austria.
Background and objective:
The Neurological Tissue Bank (NTB) of the Hospital Clínic-Institut d‘Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain is the reference center in Catalonia for the neuropathological study of prion diseases in the region since 2001. The aim of this study is to analyse the characteristics of the confirmed prion diseases registered at the NTB during the last 15 years.
Methods:
We reviewed retrospectively all neuropathologically confirmed cases registered during the period January 2001 to December 2016.
Results:
176 cases (54,3% female, mean age: 67,5 years and age range: 25-86 years) of neuropathological confirmed prion diseases have been studied at the NTB. 152 cases corresponded to sporadic Creutzfeldt-Jakob disease (sCJD), 10 to genetic CJD, 10 to Fatal Familial Insomnia, 2 to GerstmannSträussler-Scheinker disease, and 2 cases to variably protease-sensitive prionopathy (VPSPr). Within sCJD subtypes the MM1 subtype was the most frequent, followed by the VV2 histotype.
Clinical and neuropathological diagnoses agreed in 166 cases (94%). The clinical diagnosis was not accurate in 10 patients with definite prion disease: 1 had a clinical diagnosis of Fronto-temporal dementia (FTD), 1 Niemann-Pick‘s disease, 1 Lewy Body‘s Disease, 2 Alzheimer‘s disease, 1 Cortico-basal syndrome and 2 undetermined dementia. Among patients with VPSPr, 1 had a clinical diagnosis of Amyotrophic lateral sclerosis (ALS) and the other one with FTD.
Concomitant pathologies are frequent in older age groups, mainly AD neuropathological changes were observed in these subjects.
Discussion:
A wide spectrum of human prion diseases have been identified in the NTB being the relative frequencies and main characteristics like other published series. There is a high rate of agreement between clinical and neuropathological diagnoses with prion diseases. These findings show the importance that public health has given to prion diseases during the past 15 years. Continuous surveillance of human prion disease allows identification of new emerging phenotypes. Brain tissue samples from these donors are available to the scientific community. For more information please visit:
http://www.clinicbiobanc.org/banc-teixits-neurologics/mostres/en_index.html
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P192 Prion amplification techniques for the rapid evaluation of surface decontamination procedures
Bruyere-Ostells L (1), Mayran C (1), Belondrade M (1), Boublik Y (2), Haïk S (3), Fournier-Wirth C (1), Nicot S (1), Bougard D (1)
(1) Pathogenesis and control of chronic infections, Etablissement Français du Sang, Inserm, Université de Montpellier, Montpellier, France. (2) Centre de Recherche en Biologie cellulaire de Montpellier, CNRS, Université de Montpellier, Montpellier, France. (3) Inserm U 1127, CNRS UMR 7225, Sorbonne Universités, UPMC Université Paris 06 UMR S 1127, Institut du Cerveau et de la Moelle épinière, ICM, Paris, France.
Aims:
Transmissible Spongiform Encephalopathies (TSE) or prion diseases are a group of incurable and always fatal neurodegenerative disorders including Creutzfeldt-Jakob diseases (CJD) in humans. These pathologies include sporadic (sCJD), genetic and acquired (variant CJD) forms. By the past, sCJD and vCJD were transmitted by different prion contaminated biological materials to patients resulting in more than 400 iatrogenic cases (iCJD). The atypical nature and the biochemical properties of the infectious agent, formed by abnormal prion protein or PrPTSE, make it particularly resistant to conventional decontamination procedures. In addition, PrPTSE is widely distributed throughout the organism before clinical onset in vCJD and can also be detected in some peripheral tissues in sporadic CJD. Risk of iatrogenic transmission of CJD by contaminated medical device remains thus a concern for healthcare facilities. Bioassay is the gold standard method to evaluate the efficacy of prion decontamination procedures but is time-consuming and expensive. Here, we propose to compare in vitro prion amplification techniques: Protein Misfolding Cyclic Amplification (PMCA) and Real-Time Quaking Induced Conversion (RT-QuIC) for the detection of residual prions on surface after decontamination.
Methods:
Stainless steel wires, by mimicking the surface of surgical instruments, were proposed as a carrier model of prions for inactivation studies. To determine the sensitivity of the two amplification techniques on wires (Surf-PMCA and Surf-QuIC), steel wires were therefore contaminated with serial dilutions of brain homogenates (BH) from a 263k infected hamster and from a patient with sCJD (MM1 subtype). We then compared the different standard decontamination procedures including partially and fully efficient treatments by detecting the residual seeding activity on 263K and sCJD contaminated wires. We completed our study by the evaluation of marketed reagents endorsed for prion decontamination.
Results:
The two amplification techniques can detect minute quantities of PrPTSE adsorbed onto a single wire. 8/8 wires contaminated with a 10-6 dilution of 263k BH and 1/6 with the 10-8 dilution are positive with Surf-PMCA. Similar performances were obtained with Surf-QuIC on 263K: 10/16 wires contaminated with 10-6 dilution and 1/8 wires contaminated with 10-8 dilution are positive. Regarding the human sCJD-MM1 prion, Surf-QuIC allows us to detect 16/16 wires contaminated with 10-6 dilutions and 14/16 with 10-7 . Results obtained after decontamination treatments are very similar between 263K and sCJD prions. Efficiency of marketed treatments to remove prions is lower than expected.
Conclusions:
Surf-PMCA and Surf-QuIC are very sensitive methods for the detection of prions on wires and could be applied to prion decontamination studies for rapid evaluation of new treatments. Sodium hypochlorite is the only product to efficiently remove seeding activity of both 263K and sCJD prions.
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WA2 Oral transmission of CWD into Cynomolgus macaques: signs of atypical disease, prion conversion and infectivity in macaques and bio-assayed transgenic mice
Schatzl HM (1, 2), Hannaoui S (1, 2), Cheng Y-C (1, 2), Gilch S (1, 2), Beekes M (3), SchulzSchaeffer W (4), Stahl-Hennig C (5) and Czub S (2, 6)
(1) University of Calgary, Calgary Prion Research Unit, Calgary, Canada (2) University of Calgary, Faculty of Veterinary Medicine, Calgary, Canada, (3) Robert Koch Institute, Berlin, Germany, (4) University of Homburg/Saar, Homburg, Germany, (5) German Primate Center, Goettingen, Germany, (6) Canadian Food Inspection Agency (CFIA), Lethbridge, Canada.
To date, BSE is the only example of interspecies transmission of an animal prion disease into humans. The potential zoonotic transmission of CWD is an alarming issue and was addressed by many groups using a variety of in vitro and in vivo experimental systems. Evidence from these studies indicated a substantial, if not absolute, species barrier, aligning with the absence of epidemiological evidence suggesting transmission into humans. Studies in non-human primates were not conclusive so far, with oral transmission into new-world monkeys and no transmission into old-world monkeys. Our consortium has challenged 18 Cynomolgus macaques with characterized CWD material, focusing on oral transmission with muscle tissue. Some macaques have orally received a total of 5 kg of muscle material over a period of 2 years. After 5-7years of incubation time some animals showed clinical symptoms indicative of prion disease, and prion neuropathology and PrPSc deposition were found in spinal cord and brain of euthanized animals. PrPSc in immunoblot was weakly detected in some spinal cord materials and various tissues tested positive in RT-QuIC, including lymph node and spleen homogenates. To prove prion infectivity in the macaque tissues, we have intracerebrally inoculated 2 lines of transgenic mice, expressing either elk or human PrP. At least 3 TgElk mice, receiving tissues from 2 different macaques, showed clinical signs of a progressive prion disease and brains were positive in immunoblot and RT-QuIC. Tissues (brain, spinal cord and spleen) from these and preclinical mice are currently tested using various read-outs and by second passage in mice. Transgenic mice expressing human PrP were so far negative for clear clinical prion disease (some mice >300 days p.i.). In parallel, the same macaque materials are inoculated into bank voles. Taken together, there is strong evidence of transmissibility of CWD orally into macaques and from macaque tissues into transgenic mouse models, although with an incomplete attack rate. The clinical and pathological presentation in macaques was mostly atypical, with a strong emphasis on spinal cord pathology. Our ongoing studies will show whether the transmission of CWD into macaques and passage in transgenic mice represents a form of non-adaptive prion amplification, and whether macaque-adapted prions have the potential to infect mice expressing human PrP. The notion that CWD can be transmitted orally into both new-world and old-world non-human primates asks for a careful reevaluation of the zoonotic risk of CWD.
See also poster P103
***> The notion that CWD can be transmitted orally into both new-world and old-world non-human primates asks for a careful reevaluation of the zoonotic risk of CWD.
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WA16 Monitoring Potential CWD Transmission to Humans
Belay ED
Centers for Disease Control and Prevention (CDC), National Center for Emerging and Zoonotic Infectious Diseases, Atlanta, GA, USA.
The spread of chronic wasting disease (CWD) in animals has raised concerns about increasing human exposure to the CWD agent via hunting and venison consumption, potentially facilitating CWD transmission to humans. Several studies have explored this possibility, including limited epidemiologic studies, in vitro experiments, and laboratory studies using various types of animal models. Most human exposures to the CWD agent in the United States would be expected to occur in association with deer and elk hunting in CWD-endemic areas. The Centers for Disease Control and Prevention (CDC) collaborated with state health departments in Colorado, Wisconsin, and Wyoming to identify persons at risk of CWD exposure and to monitor their vital status over time. Databases were established of persons who hunted in Colorado and Wyoming and those who reported consumption of venison from deer that later tested positive in Wisconsin. Information from the databases is periodically cross-checked with mortality data to determine the vital status and causes of death for deceased persons. Long-term follow-up of these hunters is needed to assess their risk of development of a prion disease linked to CWD exposure.
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P166 Characterization of CJD strain profiles in venison consumers and non-consumers from Alberta and Saskatchewan
Stephanie Booth (1,2), Lise Lamoureux (1), Debra Sorensen (1), Jennifer L. Myskiw (1,2), Megan Klassen (1,2), Michael Coulthart (3), Valerie Sim (4)
(1) Zoonotic Diseases and Special Pathogens, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg (2) Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg (3) Canadian CJD Surveillance System, Public Health Agency of Canada, Ottawa (4) Division of Neurology, Department of Medicine Centre for Prions and Protein Folding Diseases, University of Alberta, Edmonton.
Chronic wasting disease (CWD) is spreading rapidly through wild cervid populations in the Canadian provinces of Alberta and Saskatchewan. While this has implications for tourism and hunting, there is also concern over possible zoonotic transmission to humans who eat venison from infected deer. Whilst there is no evidence of any human cases of CWD to date, the Canadian CJD Surveillance System (CJDSS) in Canada is staying vigilant. When variant CJD occurred following exposure to BSE, the unique biochemical fingerprint of the pathologic PrP enabled a causal link to be confirmed. However, we cannot be sure what phenotype human CWD prions would present with, or indeed, whether this would be distinct from that see in sporadic CJD. Therefore we are undertaking a systematic analysis of the molecular diversity of CJD cases of individuals who resided in Alberta and Saskatchewan at their time of death comparing venison consumers and non-consumers, using a variety of clinical, imaging, pathological and biochemical markers. Our initial objective is to develop novel biochemical methodologies that will extend the baseline glycoform and genetic polymorphism typing that is already completed by the CJDSS. Firstly, we are reviewing MRI, EEG and pathology information from over 40 cases of CJD to select clinically affected areas for further investigation. Biochemical analysis will include assessment of the levels of protease sensitive and resistant prion protein, glycoform typing using 2D gel electrophoresis, testing seeding capabilities and kinetics of aggregation by quaking-induced conversion, and determining prion oligomer size distributions with asymmetric flow field fractionation with in-line light scattering. Progress and preliminary data will be presented. Ultimately, we intend to further define the relationship between PrP structure and disease phenotype and establish a baseline for the identification of future atypical CJD cases that may arise as a result of exposure to CWD.
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Source Prion Conference 2018 Abstracts
http://transmissiblespongiformencephalopathy.blogspot.com/2018/05/prion-2018-may-22-25-2018-santiago-de.html
http://chronic-wasting-disease.blogspot.com/2018/07/oral-transmission-of-cwd-into.html
Prion 2018 Conference
http://prionconference.blogspot.com/2018/
Volume 24, Number 8—August 2018
Research Susceptibility of Human Prion Protein to Conversion by Chronic Wasting Disease Prions
Marcelo A. BarriaComments to Author , Adriana Libori, Gordon Mitchell, and Mark W. Head Author affiliations: National CJD Research and Surveillance Unit, University of Edinburgh, Edinburgh, Scotland, UK (M.A. Barria, A. Libori, M.W. Head); National and OIE Reference Laboratory for Scrapie and CWD, Canadian Food Inspection Agency, Ottawa, Ontario, Canada (G. Mitchell)
Abstract Chronic wasting disease (CWD) is a contagious and fatal neurodegenerative disease and a serious animal health issue for deer and elk in North America. The identification of the first cases of CWD among free-ranging reindeer and moose in Europe brings back into focus the unresolved issue of whether CWD can be zoonotic like bovine spongiform encephalopathy. We used a cell-free seeded protein misfolding assay to determine whether CWD prions from elk, white-tailed deer, and reindeer in North America can convert the human prion protein to the disease-associated form. We found that prions can convert, but the efficiency of conversion is affected by polymorphic variation in the cervid and human prion protein genes. In view of the similarity of reindeer, elk, and white-tailed deer in North America to reindeer, red deer, and roe deer, respectively, in Europe, a more comprehensive and thorough assessment of the zoonotic potential of CWD might be warranted.
snip...
Discussion Characterization of the transmission properties of CWD and evaluation of their zoonotic potential are important for public health purposes. Given that CWD affects several members of the family Cervidae, it seems reasonable to consider whether the zoonotic potential of CWD prions could be affected by factors such as CWD strain, cervid species, geographic location, and Prnp–PRNP polymorphic variation. We have previously used an in vitro conversion assay (PMCA) to investigate the susceptibility of the human PrP to conversion to its disease-associated form by several animal prion diseases, including CWD (15,16,22). The sensitivity of our molecular model for the detection of zoonotic conversion depends on the combination of 1) the action of proteinase K to degrade the abundant human PrPC that constitutes the substrate while only N terminally truncating any human PrPres produced and 2) the presence of the 3F4 epitope on human but not cervid PrP. In effect, this degree of sensitivity means that any human PrPres formed during the PMCA reaction can be detected down to the limit of Western blot sensitivity. In contrast, if other antibodies that detect both cervid and human PrP are used, such as 6H4, then newly formed human PrPres must be detected as a measurable increase in PrPres over the amount remaining in the reaction product from the cervid seed. Although best known for the efficient amplification of prions in research and diagnostic contexts, the variation of the PMCA method employed in our study is optimized for the definitive detection of zoonotic reaction products of inherently inefficient conversion reactions conducted across species barriers. By using this system, we previously made and reported the novel observation that elk CWD prions could convert human PrPC from human brain and could also convert recombinant human PrPC expressed in transgenic mice and eukaryotic cell cultures (15).
A previous publication suggested that mule deer PrPSc was unable to convert humanized transgenic substrate in PMCA assays (23) and required a further step of in vitro conditioning in deer substrate PMCA before it was able to cross the deer–human molecular barrier (24). However, prions from other species, such as elk (15) and reindeer affected by CWD, appear to be compatible with the human protein in a single round of amplification (as shown in our study). These observations suggest that different deer species affected by CWD could present differing degrees of the olecular compatibility with the normal form of human PrP.
The contribution of the polymorphism at codon 129 of the human PrP gene has been extensively studied and is recognized as a risk factor for Creutzfeldt-Jakob disease (4). In cervids, the equivalent codon corresponds to the position 132 encoding methionine or leucine. This polymorphism in the elk gene has been shown to play an important role in CWD susceptibility (25,26). We have investigated the effect of this cervid Prnp polymorphism on the conversion of the humanized transgenic substrate according to the variation in the equivalent PRNP codon 129 polymorphism. Interestingly, only the homologs methionine homozygous seed–substrate reactions could readily convert the human PrP, whereas the heterozygous elk PrPSc was unable to do so, even though comparable amounts of PrPres were used to seed the reaction. In addition, we observed only low levels of human PrPres formation in the reactions seeded with the homozygous methionine (132 MM) and the heterozygous (132 ML) seeds incubated with the other 2 human polymorphic substrates (129 MV and 129 VV). The presence of the amino acid leucine at position 132 of the elk Prnp gene has been attributed to a lower degree of prion conversion compared with methionine on the basis of experiments in mice made transgenic for these polymorphic variants (26). Considering the differences observed for the amplification of the homozygous human methionine substrate by the 2 polymorphic elk seeds (MM and ML), reappraisal of the susceptibility of human PrPC by the full range of cervid polymorphic variants affected by CWD would be warranted.
In light of the recent identification of the first cases of CWD in Europe in a free-ranging reindeer (R. tarandus) in Norway (2), we also decided to evaluate the in vitro conversion potential of CWD in 2 experimentally infected reindeer (18). Formation of human PrPres was readily detectable after a single round of PMCA, and in all 3 humanized polymorphic substrates (MM, MV, and VV). This finding suggests that CWD prions from reindeer could be more compatible with human PrPC generally and might therefore present a greater risk for zoonosis than, for example, CWD prions from white-tailed deer. A more comprehensive comparison of CWD in the affected species, coupled with the polymorphic variations in the human and deer PRNP–Prnp genes, in vivo and in vitro, will be required before firm conclusions can be drawn. Analysis of the Prnp sequence of the CWD reindeer in Norway was reported to be identical to the specimens used in our study (2). This finding raises the possibility of a direct comparison of zoonotic potential between CWD acquired in the wild and that produced in a controlled laboratory setting. (Table).
The prion hypothesis proposes that direct molecular interaction between PrPSc and PrPC is necessary for conversion and prion replication. Accordingly, polymorphic variants of the PrP of host and agent might play a role in determining compatibility and potential zoonotic risk. In this study, we have examined the capacity of the human PrPC to support in vitro conversion by elk, white-tailed deer, and reindeer CWD PrPSc. Our data confirm that elk CWD prions can convert the human PrPC, at least in vitro, and show that the homologous PRNP polymorphisms at codon 129 and 132 in humans and cervids affect conversion efficiency. Other species affected by CWD, particularly caribou or reindeer, also seem able to convert the human PrP. It will be important to determine whether other polymorphic variants found in other CWD-affected Cervidae or perhaps other factors (17) exert similar effects on the ability to convert human PrP and thus affect their zoonotic potential.
Dr. Barria is a research scientist working at the National CJD Research and Surveillance Unit, University of Edinburgh. His research has focused on understanding the molecular basis of a group of fatal neurologic disorders called prion diseases.
Acknowledgments We thank Aru Balachandran for originally providing cervid brain tissues, Abigail Diack and Jean Manson for providing mouse brain tissue, and James Ironside for his critical reading of the manuscript at an early stage.
This report is independent research commissioned and funded by the United Kingdom’s Department of Health Policy Research Programme and the Government of Scotland. The views expressed in this publication are those of the authors and not necessarily those of the Department of Health or the Government of Scotland.
Author contributions: The study was conceived and designed by M.A.B. and M.W.H. The experiments were conducted by M.A.B. and A.L. Chronic wasting disease brain specimens were provided by G.M. The manuscript was written by M.A.B. and M.W.H. All authors contributed to the editing and revision of the manuscript.
https://wwwnc.cdc.gov/eid/article/24/8/16-1888_article
https://www.ed.ac.uk/clinical-brain-sciences/news/news-jul-dec-2018/cwd-prions-human-conversion
Prion 2017 Conference Abstracts
First evidence of intracranial and peroral transmission of Chronic Wasting Disease (CWD) into Cynomolgus macaques: a work in progress
Stefanie Czub1, Walter Schulz-Schaeffer2, Christiane Stahl-Hennig3, Michael Beekes4, Hermann Schaetzl5 and Dirk Motzkus6 1 University of Calgary Faculty of Veterinary Medicine/Canadian Food Inspection Agency; 2Universitatsklinikum des Saarlandes und Medizinische Fakultat der Universitat des Saarlandes; 3 Deutsches Primaten Zentrum/Goettingen; 4 Robert-Koch-Institut Berlin; 5 University of Calgary Faculty of Veterinary Medicine; 6 presently: Boehringer Ingelheim Veterinary Research Center; previously: Deutsches Primaten Zentrum/Goettingen
This is a progress report of a project which started in 2009.
21 cynomolgus macaques were challenged with characterized CWD material from white-tailed deer (WTD) or elk by intracerebral (ic), oral, and skin exposure routes. Additional blood transfusion experiments are supposed to assess the CWD contamination risk of human blood product. Challenge materials originated from symptomatic cervids for ic, skin scarification and partially per oral routes (WTD brain). Challenge material for feeding of muscle derived from preclinical WTD and from preclinical macaques for blood transfusion experiments. We have confirmed that the CWD challenge material contained at least two different CWD agents (brain material) as well as CWD prions in muscle-associated nerves. Here we present first data on a group of animals either challenged ic with steel wires or per orally and sacrificed with incubation times ranging from 4.5 to 6.9 years at postmortem. Three animals displayed signs of mild clinical disease, including anxiety, apathy, ataxia and/or tremor. In four animals wasting was observed, two of those had confirmed diabetes. All animals have variable signs of prion neuropathology in spinal cords and brains and by supersensitive IHC, reaction was detected in spinal cord segments of all animals. Protein misfolding cyclic amplification (PMCA), real-time quaking-induced conversion (RT-QuiC) and PET-blot assays to further substantiate these findings are on the way, as well as bioassays in bank voles and transgenic mice. At present, a total of 10 animals are sacrificed and read-outs are ongoing. Preclinical incubation of the remaining macaques covers a range from 6.4 to 7.10 years. Based on the species barrier and an incubation time of > 5 years for BSE in macaques and about 10 years for scrapie in macaques, we expected an onset of clinical disease beyond 6 years post inoculation.
PRION 2017 DECIPHERING NEURODEGENERATIVE DISORDERS ABSTRACTS REFERENCE
https://aabb.confex.com/aabb/2018/mediafile/Handout/Session2756/TU1-3.pdf
8. Even though human TSE‐exposure risk through consumption of game from European cervids can be assumed to be minor, if at all existing, no final conclusion can be drawn due to the overall lack of scientific data. In particular the US data do not clearly exclude the possibility of human (sporadic or familial) TSE development due to consumption of venison. The Working Group thus recognizes a potential risk to consumers if a TSE would be present in European cervids. It might be prudent considering appropriate measures to reduce such a risk, e.g. excluding tissues such as CNS and lymphoid tissues from the human food chain, which would greatly reduce any potential risk for consumers. However, it is stressed that currently, no data regarding a risk of TSE infections from cervid products are available.
https://efsa.onlinelibrary.wiley.com/doi/full/10.2903/j.efsa.2018.5132
SATURDAY, FEBRUARY 23, 2019
Chronic Wasting Disease CWD TSE Prion and THE FEAST 2003 CDC an updated review of the science 2019
https://chronic-wasting-disease.blogspot.com/2019/02/chronic-wasting-disease-cwd-tse-prion.html
TUESDAY, NOVEMBER 04, 2014
Six-year follow-up of a point-source exposure to CWD contaminated venison in an Upstate New York community: risk behaviours and health outcomes 2005–2011 Authors, though, acknowledged the study was limited in geography and sample size and so it couldn't draw a conclusion about the risk to humans. They recommended more study. Dr. Ermias Belay was the report's principal author but he said New York and Oneida County officials are following the proper course by not launching a study. "There's really nothing to monitor presently. No one's sick," Belay said, noting the disease's incubation period in deer and elk is measured in years. "
http://chronic-wasting-disease.blogspot.com/2014/11/six-year-follow-up-of-point-source.html
Transmission Studies Mule deer transmissions of CWD were by intracerebral inoculation and compared with natural cases {the following was written but with a single line marked through it ''first passage (by this route)}....TSS resulted in a more rapidly progressive clinical disease with repeated episodes of synocopy ending in coma. One control animal became affected, it is believed through contamination of inoculum (?saline). Further CWD transmissions were carried out by Dick Marsh into ferret, mink and squirrel monkey. Transmission occurred in ALL of these species with the shortest incubation period in the ferret.
snip....
https://web.archive.org/web/20090506002237/http://www..bseinquiry.gov.uk/files/mb/m11b/tab01.pdf
2004
Jeff Swann and his Mom, cwd link... sporadic CJD?, CBC NEWS Jeff Schwan sCJD, CWD, and Professor Aguzzi on BSE and sporadic CJD
????: CBCnews
https://histodb15.usz.ch/pages/Images/videos/video-004/video-004.html
2004
April 22, 2004, 10:30 AM CDT Guests: Patrick Singh, Terry Schwan, Janet Skarbek, Bill Fielding (BEGIN VIDEOTAPE) ANNOUNCER: DEBORAH NORVILLE TONIGHT.
https://www.nbcnews.com/id/wbna4806886
1997-11-10: Panorama - The British disease
https://histodb15.usz.ch/pages/Images/videos/video-009/video-009.html
Prions in Muscles of Cervids with Chronic Wasting Disease, Norway
Volume 31, Number 2—February 2025
Research
Prions in Muscles of Cervids with Chronic Wasting Disease, Norway
Snip…
In summary, the results of our study indicate that prions are widely distributed in peripheral and edible tissues of cervids in Norway, including muscles. This finding highlights the risk of human exposure to small amounts of prions through handling and consuming infected cervids.
Appendix
https://wwwnc.cdc.gov/eid/article/31/2/24-0903-app1.pdf
https://wwwnc.cdc.gov/eid/article/31/2/24-0903_article
Volume 31, Number 2—February 2025
Dispatch
Detection of Chronic Wasting Disease Prions in Raw, Processed, and Cooked Elk Meat, Texas, USA
Snip…
Of note, our data show that exposure to high temperatures used to cook the meat increased the availability of prions for in vitro amplification. Considering the potential implications in food safety and public health, we believe that the findings described in this study warrant further research. Our results suggest that although the elk meat used in this study resisted different manipulations involved in subsequent consumption by humans, their zoonotic potential was limited. Nevertheless, even though no cases of CWD transmission to human have been reported, the potential for human infection is still unclear and continued monitoring for zoonotic potential is warranted.
https://wwwnc.cdc.gov/eid/article/31/2/24-0906_article
Detection of chronic wasting disease prions in processed meats
Results: Our results show positive prion detection in all the samples analyzed using deer and elk substrates. Surprisingly, cooked meats displayed increased seeding activities. This data suggests that CWD-prions are available to people even after meats are processed and cooked.
Conclusions: These results suggest CWD prions are accessible to humans through meats, even after processing and cooking. Considering the fact that these samples were collected from already processed specimens, the availability of CWD prions to humans is probably underestimated.
"Our results show positive prion detection in all the samples analyzed using deer and elk substrates. Surprisingly, cooked meats displayed increased seeding activities."
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
DETECTION OF CHRONIC WASTING DISEASE PRIONS IN PROCESSED MEATS.
In this study, we analyzed different processed meats derived from a pre-clinical, CWD-positive free-ranging elk. Products tested included filets, sausages, boneless steaks, burgers, ham steaks, seasoned chili meats, and spiced meats. CWD-prion presence in these products were assessed by PMCA using deer and elk substrates. Our results show positive prion detection in all products. To confirm the resilience of CWD-prions to traditional cooking methods, we grilled and boiled the meat products and evaluated them for any remnant PMCA seeding activity. Results confirmed the presence of CWD-prions in these meat products suggesting that infectious particles may still be available to people even after cooking. Our results strongly suggest ongoing human exposure to CWD-prions and raise significant concerns of zoonotic transmission through ingestion of CWD contaminated meat products.
Products tested included filets, sausages, boneless steaks, burgers, ham steaks, seasoned chili meats, and spiced meats.
CWD-prion presence in these products were assessed by PMCA using deer and elk substrates.
Our results show positive prion detection in all products.
Results confirmed the presence of CWD-prions in these meat products suggesting that infectious particles may still be available to people even after cooking.
Our results strongly suggest ongoing human exposure to CWD-prions and raise significant concerns of zoonotic transmission through ingestion of CWD contaminated meat products.
https://intcwdsympo.files.wordpress.com/2023/06/final-agenda-with-abstracts.pdf?force_download=true
So, this is what we leave our children and grandchildren?
TUESDAY, APRIL 07, 2026
APHIS USDA Captive CWD Herds Update by State March 2026
CHRONIC WASTING DISEASE CASES
Updated March 2026
https://www.aphis.usda.gov/sites/default/files/status-of-captive-herds.pdf
TUESDAY, APRIL 07, 2026
APHIS USDA Captive CWD Herds Update by State March 2026
https://chronic-wasting-disease.blogspot.com/2026/04/aphis-usda-captive-cwd-herds-update-by.html
Texas Chronic Wasting Disease CWD TSE Prion Progression 2012 to 2026, Positives to date 1282 confirmed
https://chronic-wasting-disease.blogspot.com/2026/03/texas-chronic-wasting-disease-cwd-tse.html
2026 TSE PrP
chronic wasting disease cwd, TSE, cattle, sheep, pigs, cervid, primates, humans, oh my! update 2026
USA FDA PART 589 SUBSTANCES PROHIBITED FROM USE IN ANIMAL FOOD OR FEED, CWD, Scrapie, BSE, Oh My, 2026
https://prpsc.proboards.com/thread/202/usa-fda-589-feed-broken
https://madcowfeed.blogspot.com/2026/01/usa-fda-part-589-substances-prohibited.html
Transmissible Spongiform Encephalopathy TSE
Prion Prp
Chronic Wasting Disease CWD, TSE, PrP
TSE cattle
Price of TSE Prion Poker goes up substantially, all you cattle ranchers and such, better pay close attention here...terry
"Cattle with the E211K polymorphism are susceptible to the CWD agent after oronasal exposure of 0.2 g of infectious material."
Transmission of the chronic wasting disease agent from elk to cattle after oronasal exposure
Justin Greenlee, Jifeng Bian, Zoe Lambert, Alexis Frese, and Eric Cassmann Virus and Prion Research Unit, National Animal Disease Center, USDA-ARS, Ames, IA, USA
Aims: The purpose of this study was to determine the susceptibility of cattle to chronic wasting disease agent from elk.
Materials and Methods: Initial studies were conducted in bovinized mice using inoculum derived from elk with various genotypes at codon 132 (MM, LM, LL). Based upon attack rates, inoculum (10% w/v brain homogenate) from an LM132 elk was selected for transmission studies in cattle. At approximately 2 weeks of age, one wild type steer (EE211) and one steer with the E211K polymorphism (EK211) were fed 1 mL of brain homogenate in a quart of milk replacer while another 1 mL was instilled intranasally. The cattle were examined daily for clinical signs for the duration of the experiment. One steer is still under observation at 71 months post-inoculation (mpi).
Results: Inoculum derived from MM132 elk resulted in similar attack rates and incubation periods in mice expressing wild type or K211 bovine PRNP, 35% at 531 days post inoculation (dpi) and 27% at 448 dpi, respectively. Inoculum from LM132 elk had a slightly higher attack rates in mice: 45% (693 dpi) in wild type cattle PRNP and 33% (468) in K211 mice. Inoculum from LL132 elk resulted in the highest attack rate in wild type bovinized mice (53% at 625 dpi), but no K211 mice were affected at >700 days. At approximately 70 mpi, the EK211 genotype steer developed clinical signs suggestive of prion disease, depression, low head carriage, hypersalivation, and ataxia, and was necropsied. Enzyme immunoassay (IDEXX) was positive in brainstem (OD=4.00, but non-detect in retropharyngeal lymph nodes and palatine tonsil. Immunoreactivity was largely limited to the brainstem, midbrain, and cervical spinal cord with a pattern that was primarily glia-associated.
Conclusions: Cattle with the E211K polymorphism are susceptible to the CWD agent after oronasal exposure of 0.2 g of infectious material.
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
Prion Conference 2023
Transmission of the chronic wasting disease agent from elk to cattle after oronasal exposure
Conclusions: Cattle with the E211K polymorphism are susceptible to the CWD agent after oronasal exposure of 0.2 g of infectious material.
Strain characterization of chronic wasting disease in bovine-PrP transgenic mice
Conclusions: Altogether, these results exhibit the diversity of CWD strains present in the panel of CWD isolates and the ability of at least some CWD isolates to infect bovine species. Cattle being one of the most important farming species, this ability represents a potential threat to both animal and human health, and consequently deserves further study.
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
Chronic wasting disease prions in cervids and wild pigs in North America Preliminary Outbreak Assessment DEFRA 26 January 2026
DEFRA 26 January 2026 Department for Environment, Food and Rural Affairs
Preliminary Outbreak Assessment
Chronic wasting disease prions in cervids and wild pigs in North America
26 January 2026
Disease report
Chronic wasting disease (CWD) is a fatal neurodegenerative disease of cervids, such as deer, elk, moose and reindeer. It is caused by prions – infectious proteins that cause normal cellular prion proteins to misfold (CIDRAP, 2025). The disease is widespread in captive and free-ranging cervids in North America (Figure 1). For the first time, CWD prions have also been detected in the tissues of wild pigs (Sus scrofa) caught in CWD-affected areas of the USA (Soto et al. 2025). This discovery emerged from a study designed to investigate potential interactions between wild pigs and CWD prions, as wild pigs often coexist with cervids, which can shed prions into the environment. The following assessment discusses the epidemiology of CWD in North America and the detection of CWD prions in wild pigs. It also considers the potential implications for Great Britain.
Figure 1. Distribution of CWD in cervids in North America as of 11 April 2025 (USGS, 2025).Department for Environment, Food and Rural Affairs
Situation assessment
CWD is considered one of the most important cervid diseases due to its capacity for infectious spread, high mortality rate and associated socio-economic impacts on cervid farming and hunting-related industries (Kincheloe et al., 2021, CFSPH, 2024). The disease is always fatal, with no cure or vaccine (CFSPH, 2024).
CWD was first reported among captive cervids in the USA in the 1960s (Kincheloe et al., 2021). It has since been detected in captive and or free-ranging cervids in 36 US states and 5 Canadian provinces, as well as South Korea, Norway, Finland and Sweden (Silva, 2022, USGS, 2025). While the South Korean strains are thought to have originated from North America, the European strains appear to have emerged independently (Silva, 2022).
Transmission between cervids occurs by direct contact with infected animals or indirectly, through contact with a contaminated environment, most likely via the oral route (Otero et al., 2021). The disease may also be vertically transmitted from doe to fawn (Nalls et al., 2013, Salariu et al., 2015). Environmental contamination occurs when infected animals shed infectious prions in various secretions and excretions, such as urine, faeces and saliva (Otero et al., 2021). It can also occur when infected carcasses decompose and release prions into the surrounding soil and vegetation (Miller et al., 2004). The minimum number of CWD prions required to cause infection in cervids is unknown but appears to be low (Denkers et al., 2020).
The disease is difficult to control, as infected animals can also be subclinical for months or years. During this time, they can shed CWD prions, which can remain infectious in the environment for at least 2 years (Miller et al., 2004, CFSPH, 2024). Diagnosis usually relies on post-mortem tests, which may fail to identify infected animals during the early stages of the disease (CFSPH, 2024, CIDRAP, 2025). Control efforts are further hampered by lack of evidence to inform effective CWD management and control strategies (Uehlinger et al., 2016, Mori et al., 2024).
CWD in North American cervids
CWD has been reported in a range of North American cervids, including white-tailed deer, mule deer, black-tailed deer, moose, wapiti, reindeer (captive) and red deer (captive) (EFSA BIOHAZ Panel, 2023). It was first reported in captive mule deer and black-tailed deer at research facilities in Colorado and Wyoming in the late 1960s (Otero et al., 2021). These animals were derived from wild populations. The disease was later identified in Rocky Mountain elk at these facilities and subsequently, in free-ranging populations of mule deer and elk in Wyoming and Colorado. The geographic expansion of CWD in North America is thought to reflect the commercial movement of subclinical animals and natural cervid migration (Otero et al., 2021). Epidemiological data suggest that the disease spread from the USA to Canada and then to South Korea through imports of infected cervids (Otero et al., 2021). A retrospective analysis revealed that, in 1978, a Colorado‑born mule deer at Toronto Zoo in Ontario, Canada, died of CWD (Dubé et al., 2006). In 1996, the disease was detected in captive elk in Saskatchewan (Williams and Miller, 2002).
The disease
Department for Environment, Food and Rural Affairs
has since been detected in captive cervids in Alberta and Quebec and free-ranging cervids in Alberta, British Columbia, Manitoba and Saskatchewan (USGS, 2025). The origin of the outbreak in free-ranging Canadian cervids is unknown (Otero et al., 2021).
While the spread of CWD across North America is often described as ‘rapid,’ it has been suggested that this may reflect widening disease surveillance, rather than a ‘real-time’ indication of geographic spread. CWD epidemics appear to develop relatively slowly compared with other wildlife diseases (EFSA BIOHAZ Panel, 2023). Field and modelling data from North America suggest that it may take 15 to 20 years for CWD prevalence to reach 1% in free-ranging cervid populations, although more rapid transmission may occur in captive populations. The surveillance sensitivity in North America means that the disease may have been present for 10 years or more in some areas before it was detected (Miller et al., 2000).
The prevalence of CWD in affected populations or species varies across North America. In captive herds, prevalence may reach 100% over time, while in affected free-ranging populations, reported prevalence ranges from <1% to >30%. Most clinical cases are observed in cervids 2 to 7 years old, especially males, which is believed to be due to behavioural differences rather than differences in susceptibility between sexes (EFSA BIOHAZ Panel, 2023). At least 13 different risk factors may contribute towards CWD spread in North America, such as host genetics, high deer density or inappropriate disposal of deer carcasses and slaughter by-products (EFSA BIOHAZ Panel, 2019).
Approaches towards CWD control and surveillance in captive and free-ranging deer vary widely across North America within and between jurisdictions (CIDRAP, 2025). A summary of the measures in place in each US state and Canadian province is available from the CWD Alliance (2026), a coalition of wildlife conservation agencies, dedicated to providing accurate information on CWD and supporting strategies to minimise its impact on free-ranging cervids. Wildlife agencies rely on voluntary testing of hunted deer carcasses as the main mechanism for CWD surveillance and management, usually using post-mortem ELISA or immunohistochemistry methods (CIDRAP, 2025).
In the USA, Animal and Plant Health Inspection Service (APHIS) operates the CWD Herd Certification Programme (HCP) in collaboration with state and wildlife agencies. This is a voluntary scheme which aims to provide a consistent, national approach to controlling CWD in farmed cervids and preventing interstate spread by establishing control measures such as fencing, detailed record keeping and CWD testing of all cervids over 12 months old that die for any reason. The Canadian Food Inspection Agency (CFIA) operates a similar programme, the CWD Herd Certification Programme. As of December 2025, 28 states were participating in the USA’s CWD HCP and 5 Canadian provinces and one Canadian territory were participating in the Canadian programme (USDA, 2025b, CFIA, 2025).
Control methods fall within three general categories: prevention, containment, and control and suppression. Prevention and containment aim to prevent CWDDepartment for Environment, Food and Rural Affairs introduction into areas where it has not previously been reported and to limit its geographical spread once it has been introduced, respectively. Both tend to include regulatory measures such as bans on the movement of live cervids, cervid carcasses or specified risk materials. Control and suppression aim to stabilise or reduce infection rates within a herd or population through measures such as selective or random culling (EFSA BIOHAZ Panel, 2017).
Despite control efforts, CWD has continued to spread among captive and free- ranging cervids in North America, with increasing prevalence in affected areas (Uehlinger et al., 2016, CFSPH, 2024). Eradicating CWD from North America appears infeasible due to its extent of geographic spread and epidemiological characteristics, such as environmental persistence (EFSA BIOHAZ Panel, 2017).
CWD in wild pigs in the USA
Wild pigs are an invasive population in the USA, especially in the south (Figure 2). They comprise escaped domestic swine, Eurasian wild boar and hybrids of the two (Smyser et al., 2020). Wild pigs frequently coexist with cervids in areas where CWD is endemic and may be exposed to CWD prions through rooting in contaminated soil, scavenging deer carcasses and predation on fawns. These ecological interactions provide multiple routes by which wild pigs could encounter prions from infected deer (Soto et al. 2025).
Under experimental conditions, domestic pigs can become infected with CWD by oral and intracerebral routes, suggesting that wild pigs might also be susceptible. Domestic pigs rarely develop clinical signs of CWD but accumulate prions in the lymphoid tissues in their heads and gut, suggesting that, like cervids, they could shed the prions in saliva and faeces (Moore et al., 2017).
Against this background, Soto et al. (2025) investigated potential interactions between wild pigs and CWD prions. They analysed over 300 brain and lymph node samples from 178 wild pigs living across Arkansas and Texas, USA. The animals were captured by the United States Department of Agriculture (USDA) between 2020 and 2021. None of the pigs included in the study were reported to be displaying clinical signs of disease.
Using an ultra-sensitive laboratory method (protein misfolding cyclic amplification (PMCA)), the researchers identified CWD prions in up to 37% of the lymph node samples and 15% of brain samples. The lowest detection rates were in the Texas samples (below 16%), matching the lower CWD prevalence in the state’s cervid population. These findings indicate that wild pigs are naturally exposed to CWD prions in areas where the disease is present (Soto et al., 2025).
When intracerebrally inoculated with tissues from wild pigs, a small proportion of mice expressing deer prion protein developed subclinical prion infection. No transmission was detected in mice expressing pig prion protein. This suggests that wild pig tissues only contain low levels of infectious prions and that wild pigs are relatively resistant to natural infection. However, they could still contribute to CWD transmission, influencing its epidemiology, geographic distribution and interspecies spread (Soto et al., 2025).Department for Environment, Food and Rural Affairs While their exact role and importance in CWD transmission is unclear, wild pigs have considerable home ranges in North America (1.1 to 5.32 km on average), which may increase when food is scarce. This mobility could complicate efforts to control the disease if they play a role in its transmission (Soto et al., 2025).
The USDA’s APHIS does not currently conduct active surveillance for CWD in wild pigs (USDA, 2025a).
Figure 2. Geographic distribution of wild pigs (purple) in the USA as of 27 January 2025, comprising escaped domestic pigs, Eurasian wild boar and hybrids of the two (adapted from USDA, 2026). Yellow (Texas) and green (Arkansas) circles indicate the states where CWD prions were detected in wild pig tissues.
Department for Environment, Food and Rural Affairs
Implications for Great Britain
CWD is a notifiable animal disease in Great Britain, but no cases have ever been reported (Defra and APHA, 2018, CIDRAP, 2025).
The introduction of CWD into Great Britain’s cervid population could have devastating socio-economic and animal welfare impacts, resulting in marked population declines, as seen in the USA (Miller et al., 2008). There could also be significant losses to cervid farming, hunting and rural tourism industries, as well as significant costs associated with controlling the spread of the disease. The UK venison market alone is worth an estimated £100 million (Scotland Food and Drink, 2018).
There are several discrete wild pig populations in Great Britain, including wild boar and feral pigs. The largest known population is in the Forest of Dean in Gloucestershire, with an estimated 583 wild boar as of 2025/2026, although Forestry England (2025) aims to reduce the number to 400 to protect other species, such as plants and insects. Pockets of wild boar and feral pigs exist in other parts of the country, but their exact numbers are unknown (Mathews et al., 2018). The potential impact of CWD introduction into Great Britain’s wild pig population is uncertain because their role in disease transmission remains unclear. While they appear to be relatively resistant to natural CWD infection and disease, they could potentially contribute towards the maintenance and spread of CWD in Great Britain’s cervid population (Soto et al., 2025).
To reduce the risk of CWD introduction, Great Britain suspended the import of live cervids and high-risk cervid products in June 2023, including urine hunting lures, from all countries where CWD has been reported. Fresh cervid meat, excluding offal and spinal cord, can only be imported into Great Britain from CWD-affected countries if it has tested negative for CWD using an approved diagnostic method, such as immunohistochemistry, and originates from an area where CWD has not been reported or officially suspected in the last 3 years (Defra and APHA, 2026).
The current risk of CWD prions being introduced into Great Britain’s wild pig or cervid population ranges from very low (event is very rare but cannot be excluded) to negligible (event is so rare it does not merit consideration). This is based on the risk of incursion tool, developed by Roberts et al., (2011). It is also supported by a recent Defra and APHA (2025) risk assessment. While this assessment identified a few theoretical entry pathways, such as contaminated equipment, that could not be fully assessed due to limited data, there is no definitive evidence that they have ever resulted in the introduction of CWD into a new area.
Detection of CWD prions in wild pigs in the USA is unlikely to affect Great Britain’s CWD risk level, as the USA is not approved to export live wild pigs to Great Britain (Defra, 2025). Import of infected wild pig meat or wild pig by-products from the USA could theoretically introduce CWD prions into Great Britain, but the risk of this is also very low. To date, CWD prions have only been reported in lymph node and brain tissue samples in wild pigs, at levels too low to cause disease in mouse models
Department for Environment, Food and Rural Affairs
(Soto et al., 2025). However, their presence in other tissues cannot be excluded. The USA is approved to export wild pig meat and certain wild pig by-products to Great Britain, excluding offal, minced meat and germplasm (Defra, 2025), but there appears to be limited trade in these commodities.
It is difficult to quantify the exact amount of wild pig meat exported to Great Britain, as available trade data does not always distinguish between meat of wild and domestic pigs. However, based on HMRC data, the last known export of non- domestic pig meat from the USA to Great Britain was in 2013 (4,881 kg).
Conclusion
CWD has continued to spread among captive and free-ranging cervids in North America since it was first detected in the 1960s. The finding of CWD prions in wild pigs in the USA suggests they could contribute towards transmission of the disease, influencing its epidemiology, geographic distribution and interspecies spread. However, further research is needed to confirm this. CWD has never been reported in Great Britain and the current risk of CWD prions being introduced into Great Britain’s wild pig or cervid population ranges from very low to negligible.
Readers are reminded to be vigilant for signs of CWD. Information on how to spot the disease can be found here. Suspected cases must be reported immediately to the Defra Rural Services Helpline on 03000 200 301. In Wales, call 0300 303 8268. In Scotland, contact your local Field Services Office. Failure to do so is an offence. We will continue to monitor the situation.
Authors • Lawrence Finn • Dr. Lauren Perrin • John Spiropoulos • Dr. Helen RobertsDepartment for Environment, Food and Rural Affairs
References
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https://assets.publishing.service.gov.uk/media/697a3b013c71d838df6bd413/CWD_Prions_in_Cervids_and_Wild_Pigs_in_North_America.pdf
Shedding, retention and spreading of chronic wasting disease prions in the environment
Project Number 2R01AI132695-06A1 Former Number 2R01AI132695-06 Contact PI/Project Leader MORALES, RODRIGO
Abstract Text
ABSTRACT
Chronic Wasting Disease (CWD) is a prion disease affecting natural and captive cervid populations. This disease is progressively spreading across the United States and new foci of infectivity are constantly being reported. Despite decades of research, there are still several unanswered questions concerning CWD.
Compelling evidence suggest that CWD prions enter the environment through carcasses from diseased animals or by the progressive accumulation of prions shed in excreta. Unfortunately, the role that plants, parasites, predators, and scavengers play in CWD spreading has been poorly studied. During the past funding cycle, our group made important technical and conceptual contributions in this field.
Data from our group and others (in collaboration) demonstrate that plants can bind prions into their surfaces as well as transport them from soils to leaves. This is relevant, considering that prions are shown to progressively accumulate in soils and strongly suggests plants as potential vectors for CWD transmission. Unfortunately, the previously mentioned evidence has been collected using proof-of-concept conditions, including the exposure of high titers of rodent (laboratory generated) adapted prions, and grass plants only.
We have generated preliminary data showing that carrots grown in CWD infected soil carry prions in their roots and leaves as evaluated by bioassays. In contrast, tomato plants do not share these features. The significance of these findings cannot be ignored considering the interaction of CWD prions with a human and animal edible vegetable. Considering the use of carrots roots and leaves in human and animal nutrition, and the still unknown zoonotic potential of CWD, future research involving edible plants is urgently needed.
Another relevant (published) finding from our laboratory involves the high CWD infectivity titers found in nasal bots, a common cervid parasite that develops in the nasal cavity (a hotspot of prion infectivity). These parasites are found in large quantities in CWD pre- clinical and clinical deer, and may importantly contribute to environmental CWD transmission. Our research also identified CWD prions in naturally exposed flies, ticks, and dermestid beetles. However, the prion infectivity titers in these parasites have not been evaluated.
Finally, animals other than cervids, including hunters and scavengers, are expected to be exposed to CWD prions. Interestingly, we identified CWD prions and de novo generated porcine prions in tissues from wild pigs living in areas with variable CWD epidemiology. We plan to further investigate all these events and their relevance in natural prion transmission using a complementary set of techniques, including in vitro and in vivo systems. Emphasis will be made in analyzing the strain properties and zoonotic potentials of the prion agents under investigation. For this purpose, we gathered a unique group of collaborators able to supply us with the samples and expertise required to execute this project. Outcomes from this research are expected to deliver new insights on this animal prionopathy and provide regulatory agencies with useful information to control its continuous spread.
Public Health Relevance Statement
PROJECT NARRATIVE Despite decades of research, several questions remain unanswered for the Chronic Wasting Disease (CWD) epidemic affecting several deer species in the United States. Continuing with our previous R01 project, we will explore novel factors mediating the spread of CWD prions, including different plant types, invertebrate parasites (e.g., ticks, nasal bots) and scavengers (wild boars). These potential disease vectors will be studied for their ability to transmit disease within and across species, including humans.
https://reporter.nih.gov/search/VYlhnadNtUiur19eYeRPog/project-details/11227445#description
Infectious prions in brains and muscles of domestic pigs experimentally challenged with the BSE, scrapie, and CWD agents
Authors: Francisca Bravo-Risi, Fraser Brydon, Angela Chong, Kane Spicker, Justin J. Greenlee https://orcid.org/0000-0003-2202-3054, Glenn Telling, Claudio Soto https://orcid.org/0000-0002-3412-0524, Sandra Pritzkow, Marcelo A. Barria, Rodrigo Morales
ABSTRACT
Experimental studies suggest that animal species not previously described as naturally infected by prions are susceptible to prion diseases affecting sheep, cattle, and deer. These interspecies transmissions may generate prions with unknown host ranges. Pigs are susceptible to prions from different origins, including deer chronic wasting disease (CWD), sheep scrapie, and bovine spongiform encephalopathy (BSE). Here, we studied prions in brains and muscles from pigs previously infected with these different prion sources. Specifically, we measured the total prion protein (PrP) and PK-resistant PrP by western blot. Seeding activity in these tissues was evaluated using the protein misfolding cyclic amplification (PMCA) technique. We found that BSE-infected pigs contained substantially more seeding competent prions compared with those infected with CWD and scrapie. Moreover, the zoonotic potential of porcine-BSE prions seems to be relevant, as both brains and muscles from BSE-infected pigs induced the misfolding of the human prion protein in vitro. This study helps to understand the potential fate of naturally existing prion strains in a relevant host and calls for caution considering the co-existence between feral swine and other prion-susceptible animal species.
IMPORTANCE
Prions (PrPSc) are proteinaceous, infectious pathogens responsible for prion diseases. Some livestock are highly susceptible to prion diseases. These include cattle (bovine spongiform encephalopathy, BSE), sheep and goat (scrapie), and cervids (chronic wasting disease, CWD). Unfortunately, BSE has been reported to be naturally transmitted to humans and other animal species. Domestic pigs, a relevant livestock animal, have not been reported to be naturally affected by prions; however, they are susceptible to the experimental exposure to BSE, scrapie, and CWD prions. Given the widespread consumption of porcine food products by humans, we aimed to evaluate the levels of pig-derived BSE, scrapie, and CWD prions from experimentally challenged domestic pigs in brain and meat cuts (leg, cheek meat, skirt meat, and tenderloin). We detected pig-adapted prions in the brains and some muscles of these animals. Additionally, we evaluated the in vitro compatibility between pig prions and the human prion protein (as a surrogate of zoonosis). Our results show that only pig-derived BSE prions were able to induce the misfolding of the cellular human prion protein. This data highlights the consequences of prion spillovers to other animal species and their potential availability to humans.
Snip…
In summary, our data shows the dynamic of animal prions when exposed to infectious pigs, as well as their distributions and zoonotic potentials. The data presented here may be relevant to understanding the fate of naturally existing prions in a sympatric animal species relevant for human consumption. This acquires importance considering a recent report describing the interaction between CWD and wild pigs in natural settings.
https://journals.asm.org/doi/10.1128/mbio.01800-25
Volume 31, Number 1—January 2025
Dispatch
Detection of Prions in Wild Pigs (Sus scrofa) from Areas with Reported Chronic Wasting Disease Cases, United States
Paulina Soto, Francisca Bravo-Risi, Rebeca Benavente, Tucker H. Stimming, Michael J. Bodenchuk, Patrick Whitley, Clint Turnage, Terry R. Spraker, Justin Greenlee, Glenn Telling, Jennifer Malmberg, Thomas Gidlewski, Tracy Nichols, Vienna R. Brown, and Rodrigo Morales Author affiliation: The University of Texas Health Science Center at Houston, Texas, USA (P. Soto, F. Bravo-Risi, R. Benavente, T.H. Stimming, R. Morales); Centro Integrativo de Biologia y Quimica Aplicada, Universidad Bernardo O’Higgins, Santiago, Chile (P. Soto, F. Bravo-Risi, R. Morales); US Department of Agriculture, Fort Collins, Colorado, USA (M.J. Bodenchuk, P. Whitley, C. Turnage, J. Malmberg, T. Gidlewski, T. Nichols, V.R. Brown); Colorado State University, Fort Collins, Colorado, USA (T.R. Spraker, G. Telling); US Department of Agriculture, Ames, Iowa, USA (J. Greenlee)
Abstract
Using a prion amplification assay, we identified prions in tissues from wild pigs (Sus scrofa) living in areas of the United States with variable chronic wasting disease (CWD) epidemiology. Our findings indicate that scavenging swine could play a role in disseminating CWD and could therefore influence its epidemiology, geographic distribution, and interspecies spread.
Chronic wasting disease (CWD) is a prion disease of particular concern because of its uncontrolled contagious spread among various cervid species in North America https://www.usgs.gov/media/images/distribution-chronic-wasting-disease-north-america
its recent discovery in Nordic countries (1), and its increasingly uncertain zoonotic potential (2). CWD is the only animal prion disease affecting captive as well as wild animals. Persistent shedding of prions by CWD-affected animals and resulting environmental contamination is considered a major route of transmission contributing to spread of the disease. Carcasses of CWD-affected animals represent relevant sources of prion infectivity to multiple animal species that can develop disease or act as vectors to spread infection to new locations.
Free-ranging deer are sympatric with multiple animal species, including some that act as predators, scavengers, or both. Experimental transmissions to study the potential for interspecies CWD transmissions have been attempted in raccoons, ferrets, cattle, sheep, and North American rodents (3–7). Potential interspecies CWD transmission has also been addressed using transgenic (Tg) mice expressing prion proteins (PrP) from relevant animal species (8). Although no reports of natural interspecies CWD transmissions have been documented, experimental studies strongly suggest the possibility for interspecies transmission in nature exists (3–7). Inoculation and serial passage studies reveal the potential of CWD prions to adapt to noncervid species, resulting in emergence of novel prion strains with unpredicted features (9–11).
Wild pigs (Sus scrofa), also called feral swine, are an invasive population comprising domestic swine, Eurasian wild boar, and hybrids of the 2 species (12). Wild pig populations have become established in the United States (Appendix Figure 1, panel A), enabled by their high rates of fecundity; omnivorous and opportunistic diet; and widespread, often human-mediated movement (13). Wild pigs scavenge carcasses on the landscape and have an intimate relationship with the soil because of their routine rooting and wallowing behaviors (14). CWD prions have been experimentally transmitted to domestic pigs by intracerebral and oral exposure routes (15), which is relevant because wild pigs coexist with cervids in CWD endemic areas and reportedly prey on fawns and scavenge deer carcasses. Considering the species overlap in many parts of the United States (Appendix Figure 1, panel), we studied potential interactions between wild pigs and CWD prions.
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Conclusions
In summary, results from this study showed that wild pigs are exposed to cervid prions, although the pigs seem to display some resistance to infection via natural exposure. Future studies should address the susceptibility of this invasive animal species to the multiple prion strains circulating in the environment. Nonetheless, identification of CWD prions in wild pig tissues indicated the potential for pigs to move prions across the landscape, which may, in turn, influence the epidemiology and geographic spread of CWD.
https://wwwnc.cdc.gov/eid/article/31/1/24-0401_article
Title: Disease-associated prion protein detected in lymphoid tissues from pigs challenged with the agent of chronic wasting disease
Conclusions: This study demonstrates that PrPSc accumulates in lymphoid tissues from pigs challenged intracranially or orally with the CWD agent, and can be detected as early as 4 months after challenge. CWD-infected pigs rarely develop clinical disease and if they do, they do so after a long incubation period. This raises the possibility that CWD-infected pigs could shed prions into their environment long before they develop clinical disease. Furthermore, lymphoid tissues from CWD-infected pigs could present a potential source of CWD infectivity in the animal and human food chains…
https://www.ars.usda.gov/research/publications/publication/?seqNo115=337105
Chronic wasting disease prions in cervids and wild pigs in North America Preliminary Outbreak Assessment DEFRA 26 January 2026
https://transmissiblespongiformencephalopathy.blogspot.com/2026/01/chronic-wasting-disease-prions-in.html
https://prpsc.proboards.com/thread/190/confucius-ponders-wild-pigs-scrofa
https://chronic-wasting-disease.blogspot.com/2026/01/confucius-ponders-what-about-wild-pigs.html
TSE cervid
PLoS One. 2020 Aug 20;15(8):e0237410. doi: 10.1371/journal.pone.0237410. eCollection 2020.
Very low oral exposure to prions of brain or saliva origin can transmit chronic wasting disease
Nathaniel D Denkers 1 , Clare E Hoover 2 , Kristen A Davenport 3 , Davin M Henderson 1 , Erin E McNulty 1 , Amy V Nalls 1 , Candace K Mathiason 1 , Edward A Hoover 1
PMID: 32817706 PMCID: PMC7446902 DOI: 10.1371/journal.pone.0237410
Abstract
The minimum infectious dose required to induce CWD infection in cervids remains unknown, as does whether peripherally shed prions and/or multiple low dose exposures are important factors in CWD transmission. With the goal of better understand CWD infection in nature, we studied oral exposures of deer to very low doses of CWD prions and also examined whether the frequency of exposure or prion source may influence infection and pathogenesis. We orally inoculated white-tailed deer with either single or multiple divided doses of prions of brain or saliva origin and monitored infection by serial longitudinal tissue biopsies spanning over two years. We report that oral exposure to as little as 300 nanograms (ng) of CWD-positive brain or to saliva containing seeding activity equivalent to 300 ng of CWD-positive brain, were sufficient to transmit CWD disease. This was true whether the inoculum was administered as a single bolus or divided as three weekly 100 ng exposures. However, when the 300 ng total dose was apportioned as 10, 30 ng doses delivered over 12 weeks, no infection occurred. While low-dose exposures to prions of brain or saliva origin prolonged the time from inoculation to first detection of infection, once infection was established, we observed no differences in disease pathogenesis. These studies suggest that the CWD minimum infectious dose approximates 100 to 300 ng CWD-positive brain (or saliva equivalent), and that CWD infection appears to conform more with a threshold than a cumulative dose dynamic.
Snip…
Discussion
As CWD expands across North America and Scandinavia, how this disease is transmitted so efficiently remains unclear, given the low concentrations of prions shed in secretions and excretions [13, 14]. The present studies demonstrated that a single oral exposure to as little as 300nmg of CWD-positive brain or equivalent saliva can initiate infection in 100% of exposed white-tailed deer. However, distributing this dose as 10, 30 ng exposures failed to induce infection. Overall, these results suggest that the minimum oral infectious exposure approaches 100 to 300 ng of CWD-positive brain equivalent. These dynamics also invite speculation as to whether potential infection co-factors, such as particle binding [46, 47] or compromises in mucosal integrity may influence infection susceptibility, as suggested from two studies in rodent models [48, 49].
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0237410
PRION 2023 CONTINUED;
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
Prion 2023 Experimental Oronasal Inoculation of the Chronic Wasting Disease Agent into White Tailed Deer
Author list: Sarah Zurbuchena,b , S. Jo Moorea,b , Jifeng Biana , Eric D. Cassmanna , and Justin J. Greenleea . a. Virus and Prion Research Unit, National Animal Disease Center, ARS, United States Department of Agriculture, Ames, IA, US b. Oak Ridge Institute for Science and Education (ORISE), U.S. Department of Energy, Oak Ridge, TN, United States
Aims: The purpose of this experiment was to determine whether white-tailed deer (WTD) are susceptible to inoculation of chronic wasting disease (CWD) via oronasal exposure.
Materials and methods: Six male, neutered WTD were oronasally inoculated with brainstem material (10% w/v) from a CWD-positive wild-type WTD. The genotypes of five inoculated deer were Q95/G96 (wild-type). One inoculated deer was homozygous S at codon 96 (96SS). Cervidized (Tg12; M132 elk PrP) mice were inoculated with 1% w/v brainstem homogenate from either a 96GG WTD (n=10) or the 96SS WTD (n=10).
Results: All deer developed characteristic clinical signs of CWD including weight loss, regurgitation, and ataxia. The 96SS individual had a prolonged disease course and incubation period compared to the other deer. Western blots of the brainstem on all deer yielded similar molecular profiles. All deer had widespread lymphoid distribution of PrPCWD and neuropathologic lesions associated with transmissible spongiform encephalopathies. Both groups of mice had a 100% attack rate and developed clinical signs, including loss of body condition, ataxia, and loss of righting reflex. Mice inoculated with material from the 96SS deer had a significantly shorter incubation period than mice inoculated with material from 96GG deer (Welch two sample T-test, P<0.05). Serial dilutions of each inocula suggests that differences in incubation period were not due to a greater concentration of PrPCWD in the 96SS inoculum. Molecular profiles from western blot of brain homogenates from mice appeared similar regardless of inoculum and appear similar to those of deer used for inoculum.
Conclusions: This study characterizes the lesions and clinical course of CWD in WTD inoculated in a similar manner to natural conditions. It supports previous findings that 96SS deer have a prolonged disease course. Further, it describes a first pass of inoculum from a 96SS deer in cervidized mice which shortened the incubation period.
Funded by: This research was funded in its entirety by congressionally appropriated funds to the United States Department of Agriculture, Agricultural Research Service. The funders of the work did not influence study design, data collection, analysis, decision to publish, or preparation of the manuscript.
Acknowledgement: We thank Ami Frank and Kevin Hassall for their technical contributions to this project.
=====end
PRION 2023 CONTINUED;
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
Camel Prion Disease PrP
Thursday, February 19, 2026
Identification of Camel Prion Disease in Tunisia: evidence of an emerging prion disease in North Africa
https://camelusprp.blogspot.com/2026/02/identification-of-camel-prion-disease.html
Raccoon TSE PrP
The chronic wasting disease agent from white-tailed deer is highly infectious to humanized mice after passage through raccoons
https://www.ars.usda.gov/research/publications/publication/?seqNo115=400777
SATURDAY, FEBRUARY 28, 2026
atypical Nor-98, CH1641, Scrapie, TSE Prion, Update 2026
https://nor-98.blogspot.com/2026/02/atypical-nor-98-ch1641-scrapie-tse.html
SATURDAY, APRIL 11, 2026
Chronic Wasting Disease CWD TSE PrP, Cervid, Genetic Manipulation, Unforeseen Circumstances
https://chronic-wasting-disease.blogspot.com/2026/04/chronic-wasting-disease-cwd-tse-prp.html
APHIS USDA Captive CWD Herds Update by State March 2026
Updated March 2026
https://www.aphis.usda.gov/sites/default/files/status-of-captive-herds.pdf
https://chronic-wasting-disease.blogspot.com/2026/04/aphis-usda-captive-cwd-herds-update-by.html
Scrapie, CWD, BSE, CJD, TSE, PrP Update 2026
***> CWD Action Plan National Program 103 Animal Health 2022-2027 UPDATE JANUARY 2026
https://prpsc.proboards.com/thread/189/action-national-program-animal-health
https://chronic-wasting-disease.blogspot.com/2026/01/cwd-action-plan-national-program-103.html
***> SCRAPIE TSE Prion USA RAPID RESPONSE URGENT UPDATES DECEMBER 25, 2025
***> CWD vs Scrapie Urgent Update
https://scrapie-usa.blogspot.com/2025/12/scrapie-tse-prion-usa-rapid-response.html
https://prpsc.proboards.com/thread/186/scrapie-prion-response-urgent-updates
***> 2026 USDA EXPLANATORY NOTES, APHIS, CWD, BSE, Scrapie, TSE, Prion
https://transmissiblespongiformencephalopathy.blogspot.com/2025/12/2026-usda-explanatory-notes-aphis-cwd.html
USDA National Scrapie Program History and Bovine Spongiform Encephalopathy BSE TSE Update 2025 and history there from
https://www.researchgate.net/publication/396084947_USDA_National_Scrapie_Program_History_and_Bovine_Spongiform_Encephalopathy_BSE_TSE0AUpdate_2
TUESDAY, JANUARY 20, 2026
Pathogenesis, Transmission and Detection of Zoonotic Prion Diseases Project Number 5P01AI077774-14 2025
https://chronic-wasting-disease.blogspot.com/2026/01/pathogenesis-transmission-and-detection.html
TUESDAY, SEPTEMBER 30, 2025
USDA National Scrapie Program History and Bovine Spongiform Encephalopathy BSE TSE Update 2025
https://bovineprp.blogspot.com/2025/09/usda-national-scrapie-program-history.html
https://scrapie-usa.blogspot.com/2025/09/usda-national-scrapie-program-history.html
Control of Chronic Wasting Disease OMB Control Number: 0579-0189APHIS-2021-0004 Singeltary Submission
https://www.regulations.gov/comment/APHIS-2021-0004-0002
https://downloads.regulations.gov/APHIS-2021-0004-0002/attachment_1.pdf
Docket No. APHIS-2018-0011 Chronic Wasting Disease Herd Certification
https://www.regulations.gov/document/APHIS-2018-0011-0003
https://downloads.regulations.gov/APHIS-2018-0011-0003/attachment_1.pdf
Docket No. FDA-2003-D-0432 (formerly 03D-0186) Use of Material from Deer and Elk in Animal Feed
PUBLIC SUBMISSION
Comment from Terry Singeltary Sr.
Posted by the Food and Drug Administration on May 17, 2016 Comment
Docket No. FDA-2003-D-0432 (formerly 03D-0186) Use of Material from Deer and Elk in Animal Feed Singeltary Submission
https://www.regulations.gov/comment/FDA-2003-D-0432-0011
https://www.regulations.gov/docket/FDA-2003-D-0432
SUNDAY, MARCH 8, 2026
Texas Creutzfeldt-Jakob Disease Deaths and Death Rates per Year (2013-2022) More Than Tripled, and case reporting has ceased since then
https://cjdtexas.blogspot.com/2026/03/texas-creutzfeldt-jakob-disease-deaths.html
https://prpsc.proboards.com/thread/209/texas-cases-more-triples-2013
WEDNESDAY, OCTOBER 15, 2025
US NATIONAL PRION DISEASE PATHOLOGY SURVEILLANCE CENTER CJD TSE REPORT 2025
https://prionunitusaupdate.blogspot.com/2025/10/us-national-prion-disease-pathology.html
FRIDAY, NOVEMBER 21, 2025
While no one was watching: Tenuous status of CDC prion unit, risk of CWD to people worry scientists
https://chronic-wasting-disease.blogspot.com/2025/11/while-no-one-was-watching-tenuous.html
SATURDAY, JANUARY 10, 2026
Neuropsychiatric symptoms in sporadic Creutzfeldt-Jakob disease, a review
https://creutzfeldt-jakob-disease.blogspot.com/2026/01/neuropsychiatric-symptoms-in-sporadic.html
https://prpsc.proboards.com/thread/191/neuropsychiatric-symptoms-sporadic-cjd-review
SUNDAY, MARCH 23, 2025
Creutzfeldt Jakob Disease TSE Prion Increasing 2025 Update
https://creutzfeldt-jakob-disease.blogspot.com/2025/03/creutzfeldt-jakob-disease-tse-prion.html
FRIDAY, DECEMBER 13, 2024
Creutzfeldt Jacob Disease CJD, BSE, CWD, TSE Prion, December 14, 2024 Annual Update
https://creutzfeldt-jakob-disease.blogspot.com/2024/12/creutzfeldt-jacob-disease-cjd-bse-cwd.html
Terry S. Singeltary Sr. Bacliff, Texas 77518 flounder9@verizon.net
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
Prion 2023 Experimental Oronasal Inoculation of the Chronic Wasting Disease Agent into White Tailed Deer
Author list: Sarah Zurbuchena,b , S. Jo Moorea,b , Jifeng Biana , Eric D. Cassmanna , and Justin J. Greenleea . a. Virus and Prion Research Unit, National Animal Disease Center, ARS, United States Department of Agriculture, Ames, IA, US b. Oak Ridge Institute for Science and Education (ORISE), U.S. Department of Energy, Oak Ridge, TN, United States
Aims: The purpose of this experiment was to determine whether white-tailed deer (WTD) are susceptible to inoculation of chronic wasting disease (CWD) via oronasal exposure.
Materials and methods: Six male, neutered WTD were oronasally inoculated with brainstem material (10% w/v) from a CWD-positive wild-type WTD. The genotypes of five inoculated deer were Q95/G96 (wild-type). One inoculated deer was homozygous S at codon 96 (96SS). Cervidized (Tg12; M132 elk PrP) mice were inoculated with 1% w/v brainstem homogenate from either a 96GG WTD (n=10) or the 96SS WTD (n=10).
Results: All deer developed characteristic clinical signs of CWD including weight loss, regurgitation, and ataxia. The 96SS individual had a prolonged disease course and incubation period compared to the other deer. Western blots of the brainstem on all deer yielded similar molecular profiles. All deer had widespread lymphoid distribution of PrPCWD and neuropathologic lesions associated with transmissible spongiform encephalopathies. Both groups of mice had a 100% attack rate and developed clinical signs, including loss of body condition, ataxia, and loss of righting reflex. Mice inoculated with material from the 96SS deer had a significantly shorter incubation period than mice inoculated with material from 96GG deer (Welch two sample T-test, P<0.05). Serial dilutions of each inocula suggests that differences in incubation period were not due to a greater concentration of PrPCWD in the 96SS inoculum. Molecular profiles from western blot of brain homogenates from mice appeared similar regardless of inoculum and appear similar to those of deer used for inoculum.
Conclusions: This study characterizes the lesions and clinical course of CWD in WTD inoculated in a similar manner to natural conditions. It supports previous findings that 96SS deer have a prolonged disease course. Further, it describes a first pass of inoculum from a 96SS deer in cervidized mice which shortened the incubation period.
Funded by: This research was funded in its entirety by congressionally appropriated funds to the United States Department of Agriculture, Agricultural Research Service. The funders of the work did not influence study design, data collection, analysis, decision to publish, or preparation of the manuscript.
Acknowledgement: We thank Ami Frank and Kevin Hassall for their technical contributions to this project.
=====end
PRION 2023 CONTINUED;
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
Camel Prion Disease PrP
Thursday, February 19, 2026
Identification of Camel Prion Disease in Tunisia: evidence of an emerging prion disease in North Africa
https://camelusprp.blogspot.com/2026/02/identification-of-camel-prion-disease.html
Raccoon TSE PrP
The chronic wasting disease agent from white-tailed deer is highly infectious to humanized mice after passage through raccoons
https://www.ars.usda.gov/research/publications/publication/?seqNo115=400777
SATURDAY, FEBRUARY 28, 2026
atypical Nor-98, CH1641, Scrapie, TSE Prion, Update 2026
https://nor-98.blogspot.com/2026/02/atypical-nor-98-ch1641-scrapie-tse.html
SATURDAY, APRIL 11, 2026
Chronic Wasting Disease CWD TSE PrP, Cervid, Genetic Manipulation, Unforeseen Circumstances
https://chronic-wasting-disease.blogspot.com/2026/04/chronic-wasting-disease-cwd-tse-prp.html
APHIS USDA Captive CWD Herds Update by State March 2026
Updated March 2026
https://www.aphis.usda.gov/sites/default/files/status-of-captive-herds.pdf
https://chronic-wasting-disease.blogspot.com/2026/04/aphis-usda-captive-cwd-herds-update-by.html
Scrapie, CWD, BSE, CJD, TSE, PrP Update 2026
***> CWD Action Plan National Program 103 Animal Health 2022-2027 UPDATE JANUARY 2026
https://prpsc.proboards.com/thread/189/action-national-program-animal-health
https://chronic-wasting-disease.blogspot.com/2026/01/cwd-action-plan-national-program-103.html
***> SCRAPIE TSE Prion USA RAPID RESPONSE URGENT UPDATES DECEMBER 25, 2025
***> CWD vs Scrapie Urgent Update
https://scrapie-usa.blogspot.com/2025/12/scrapie-tse-prion-usa-rapid-response.html
https://prpsc.proboards.com/thread/186/scrapie-prion-response-urgent-updates
***> 2026 USDA EXPLANATORY NOTES, APHIS, CWD, BSE, Scrapie, TSE, Prion
https://transmissiblespongiformencephalopathy.blogspot.com/2025/12/2026-usda-explanatory-notes-aphis-cwd.html
USDA National Scrapie Program History and Bovine Spongiform Encephalopathy BSE TSE Update 2025 and history there from
https://www.researchgate.net/publication/396084947_USDA_National_Scrapie_Program_History_and_Bovine_Spongiform_Encephalopathy_BSE_TSE0AUpdate_2
TUESDAY, JANUARY 20, 2026
Pathogenesis, Transmission and Detection of Zoonotic Prion Diseases Project Number 5P01AI077774-14 2025
https://chronic-wasting-disease.blogspot.com/2026/01/pathogenesis-transmission-and-detection.html
TUESDAY, SEPTEMBER 30, 2025
USDA National Scrapie Program History and Bovine Spongiform Encephalopathy BSE TSE Update 2025
https://bovineprp.blogspot.com/2025/09/usda-national-scrapie-program-history.html
https://scrapie-usa.blogspot.com/2025/09/usda-national-scrapie-program-history.html
Control of Chronic Wasting Disease OMB Control Number: 0579-0189APHIS-2021-0004 Singeltary Submission
https://www.regulations.gov/comment/APHIS-2021-0004-0002
https://downloads.regulations.gov/APHIS-2021-0004-0002/attachment_1.pdf
Docket No. APHIS-2018-0011 Chronic Wasting Disease Herd Certification
https://www.regulations.gov/document/APHIS-2018-0011-0003
https://downloads.regulations.gov/APHIS-2018-0011-0003/attachment_1.pdf
Docket No. FDA-2003-D-0432 (formerly 03D-0186) Use of Material from Deer and Elk in Animal Feed
PUBLIC SUBMISSION
Comment from Terry Singeltary Sr.
Posted by the Food and Drug Administration on May 17, 2016 Comment
Docket No. FDA-2003-D-0432 (formerly 03D-0186) Use of Material from Deer and Elk in Animal Feed Singeltary Submission
https://www.regulations.gov/comment/FDA-2003-D-0432-0011
https://www.regulations.gov/docket/FDA-2003-D-0432
SUNDAY, MARCH 8, 2026
Texas Creutzfeldt-Jakob Disease Deaths and Death Rates per Year (2013-2022) More Than Tripled, and case reporting has ceased since then
https://cjdtexas.blogspot.com/2026/03/texas-creutzfeldt-jakob-disease-deaths.html
https://prpsc.proboards.com/thread/209/texas-cases-more-triples-2013
WEDNESDAY, OCTOBER 15, 2025
US NATIONAL PRION DISEASE PATHOLOGY SURVEILLANCE CENTER CJD TSE REPORT 2025
https://prionunitusaupdate.blogspot.com/2025/10/us-national-prion-disease-pathology.html
FRIDAY, NOVEMBER 21, 2025
While no one was watching: Tenuous status of CDC prion unit, risk of CWD to people worry scientists
https://chronic-wasting-disease.blogspot.com/2025/11/while-no-one-was-watching-tenuous.html
SATURDAY, JANUARY 10, 2026
Neuropsychiatric symptoms in sporadic Creutzfeldt-Jakob disease, a review
https://creutzfeldt-jakob-disease.blogspot.com/2026/01/neuropsychiatric-symptoms-in-sporadic.html
https://prpsc.proboards.com/thread/191/neuropsychiatric-symptoms-sporadic-cjd-review
SUNDAY, MARCH 23, 2025
Creutzfeldt Jakob Disease TSE Prion Increasing 2025 Update
https://creutzfeldt-jakob-disease.blogspot.com/2025/03/creutzfeldt-jakob-disease-tse-prion.html
FRIDAY, DECEMBER 13, 2024
Creutzfeldt Jacob Disease CJD, BSE, CWD, TSE Prion, December 14, 2024 Annual Update
https://creutzfeldt-jakob-disease.blogspot.com/2024/12/creutzfeldt-jacob-disease-cjd-bse-cwd.html
Terry S. Singeltary Sr. Bacliff, Texas 77518 flounder9@verizon.net
