Chronic Wasting Disease CWD TSE Prion, Economical, Environmental, Zoonotic, Risk Factors 2026
Chronic Wasting Disease CWD TSE PrP transmission to, Cattle, Sheep, Pigs, Cervid, Primates, oh my!
CWD TSE Prion Poker, are we all in yet $$$
Farmed, Wild, Tribal, Cervid Chronic Wasting Disease Management and Response Activities 2023 Cooperative Agreements 2023 Spending Plan
Farmed Cervid Chronic Wasting Disease Management and Response Activities 2023 Cooperative Agreements 2023 Spending Plan
https://www.aphis.usda.gov/sites/default/files/2023-cwd-spending-plan.pdf
Wild Cervid Chronic Wasting Disease Management and Response Activities 2023 Cooperative Agreements 2023 Spending Plan August 2023
https://www.aphis.usda.gov/sites/default/files/fy23-ws-cwd-spending-plan.pdf
USDA APHIS Tribal Nations Wild Cervid Chronic Wasting Disease Opportunities 2023 Cooperative Agreements 2023 Spending Plan
https://www.aphis.usda.gov/sites/default/files/fy23-tribal-cwd-spending-plan.pdf
USAHA 129th Annual Meeting CWD TSE PrP 2025 and a Decade Review
USAHA 129th Annual Meeting CWD TSE PrP 2025 and a Decade Review of Progress, or not so much, of the attempts to try and eradicate, or at least control the spread of Chronic Wasting Disease CWD TSE PrP. i put that in AI Google, too see what would come up… terry
to AI trials and tribulations and failures of science of CWD Transmissible Spongiform Encephalopathy
AI answer; The scientific pursuit to understand, detect, and control Chronic Wasting Disease (CWD)—a Transmissible Spongiform Encephalopathy (TSE) affecting cervids—has been characterized by significant, long-term challenges, slow progress, and frustrating management failures. CWD is a 100% fatal, infectious, and resilient prion disease that has spread to 24 U.S. states, 3 Canadian provinces, South Korea, and Norway, defying many traditional wildlife management strategies.
Here is an overview of the trials, tribulations, and failures of CWD science:
1. Scientific Tribulations and Challenges Insidious Nature of Prions: Unlike bacteria or viruses, prions are misfolded proteins that are extremely resilient. They resist traditional disinfection, freezing, incineration below 1100°F, radiation, and desiccation. They persist in the environment for years, making containment nearly impossible.
Long Incubation Periods: CWD has a long pre-clinical phase where animals look healthy but shed prions, with incubation ranging from 15 to over 34 months. This makes early detection in wild populations exceptionally difficult.
Environmental Reservoirs: Research has struggled to map how prions bind to soil and minerals, which creates long-lasting "hotspots" of infection.
Diagnostic Limitations: While post-mortem testing of lymph nodes or brain tissue is accurate, it is not practical for massive, live wild populations. Live-animal testing (e.g., rectal biopsy) is less sensitive and cannot effectively monitor the scale of the spread.
2. Scientific Failures and Unresolved Questions Inconclusive Zoonotic Risk: A major failure of scientific communication and research has been the inability to definitively rule out whether CWD can infect humans. While no cases have been reported, laboratory studies on transgenic mice and macaques have yielded mixed results, leading to a "high level of uncertainty".
Failed Containment: Management strategies, including population reduction and, in some cases, eradication of infected herds, have largely failed to halt the spread in the wild. The disease continues to spread geographically and increase in prevalence.
Inconsistent Data: Studies on management, such as culling, have produced conflicting results, with some showing effectiveness and others showing no difference.
3. Management and Policy Failures Captive Herd Industry: A major, ongoing failure is the inability to strictly regulate the captive deer industry, which has acted as a primary driver of long-distance, artificial spread of the disease.
Inconsistent Governance: State wildlife agencies have often failed to apply consistent, science-based regulations, bowing to pressure from the captive deer industry, leading to loopholes in testing and, in some cases, the spread of the disease through the movement of contaminated, farmed deer.
Human Activity Drivers: Failure to curb human-caused concentration of animals, such as baiting and feeding, has worsened the spread.
4. Recent Scientific Advancements (The Path Forward) Ultrasensitive Detection (RT-QuIC): The development of Real-Time Quaking-Induced Conversion (RT-QuIC) and Serial Protein Misfolding Amplification (PMCA) has allowed scientists to detect very low levels of prions, improving the ability to identify prions in soil, water, and even in live animals (e.g., in feces or saliva).
Better Environmental Sampling: Techniques to sample contaminated, environmentally relevant surfaces like metal fences or water sources are now being developed.
The science of CWD has moved from a lack of understanding to a state of high alarm, driven by the realization that this disease is not just a localized issue but a persistent, growing threat to wildlife, ecosystems, and potentially human health. end…TSS
not bad.
please let me elaborate on the dire consequences we face with CWD TSE PrP, if we fail to act swiftly, with sound science, and NOT let the industry continue to legislate junk science, and regulations there from, by trucking CWD to hell and back, no better example is Texas…
USAHA 129th Annual Meeting CWD TSE PrP 2025 and a Decade Review
https://www.researchgate.net/publication/400772766_USAHA_129th_Annual_Meeting_CWD_TSE_PrP_2025_and_a_Decade_Review
USAHA 129th Annual Meeting CWD TSE PrP 2025 and a Decade Review
2025 AAVLD/USAHA 129th Annual Meeting CWD TSE PrP October 30, 2025 - November 5, 2025
https://chronic-wasting-disease.blogspot.com/2026/02/usaha-129th-annual-meeting-cwd-tse-prp.html
https://prpsc.proboards.com/thread/205/usaha-129th-annual-decade-review
Docket No. APHIS-2018-0011 Chronic Wasting Disease Herd Certification Program Standards Singeltary Submission March 30, 2018
Greetings APHIS, USDA, Dr. Tracy Nichols, et al,
I wish to kindly submit my comments on the Docket No. APHIS-2018-0011 Chronic Wasting Disease Herd Certification Program Standards please. i have submitted online and sent a hard copy to Dr. Nichols via email. i know that my concern may not be the same concern as others, but ramifications from cwd tse prion can be long lasting, and science is still emerging. however, the science today warrants immediate and further actions be taken, especially about zoonosis potential for cwd tse prion, if it has not happened already. my comments, with reference materials, are as follows, and will be formatted in such a way, i will address issues by numbers 1-10, and under each one of my comments by each number, i will reference my comments with science to back up what i am stating/asking...thank you kindly, terry
1. I believe that immediately, there should be a 'DECLARATION OF EXTRAORDINARY EMERGENCY FOR FOREIGN ANIMAL DISEASE OF THE United States of America USA' due to Chronic Wasting Disease CWD Transmissible Spongiform Encephalopathy TSE Prion disease. All Intercontinental, International, Interstate movements of cervid should be banned immediately from the USA, and documented CWD TSE Prion Countries. ...snip...see full text Singeltary Submission for references.
2. Voluntary Chronic Wasting Disease Herd Certification Program should be made MANDATORY immediately, OR NO PERMIT TO FARM DEER OR ELK, PERIOD! you don't want to join, then fine, you don't farm cervid and or any product there from...see full text Singeltary Submission for references.
3. INDEMNITY, NO MORE Federal indemnity program, or what i call, ENTITLEMENT PROGRAM for game farm industry. NO MORE BAIL OUTS FROM TAX PAYERS. if the captive industry can't buy insurance to protect not only themselves, but also their customers, and especially the STATE, from Chronic Wasting Disease CWD TSE Prion or what some call mad deer disease and harm therefrom, IF they can't afford to buy that insurance that will cover all of it, then they DO NOT GET A PERMIT to have a game farm for anything. This CWD TSE Prion can/could/has caused property values to fall from some reports in some places. roll the dice, how much is a state willing to lose?...see full text Singeltary Submission for references.
4. QUARANTINE OF ALL CAPTIVE, BREEDERS, URINE, ANTLER, VELVET, SPERM, OR ANY FACILITY that has been confirmed to have Chronic Wasting Disease CWD TSE Prion, the QUARANTINE should be for 21 years due to science showing what scrapie can do. 5 years is NOT enough. see; Infectious agent of sheep scrapie may persist in the environment for at least 16 years...snip...see full text Singeltary Submission for references.
PLEASE SEE Singeltary 5 - 10 comoments, and full text file DOWNLOAD ON GOVERNMENT SITE, OR GO TO THIS URL LINK FOR FULL TEXT OF SINGELTARY SUBMISSION TO Docket No. APHIS-2018-0011 Chronic Wasting Disease Herd Certification Program Standards Singeltary Submission March 30, 2018, PLEASE SEE;
https://www.regulations.gov/document/APHIS-2018-0011-0003
https://downloads.regulations.gov/APHIS-2018-0011-0003/attachment_1.pdf
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. 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
APHIS Indemnity Regulations [Docket No. APHIS-2021-0010] RIN 0579-AE65 Singeltary Comment Submission
Comment from Singeltary Sr., Terry
Posted by the Animal and Plant Health Inspection Service on Sep 8, 2022
https://www.regulations.gov/comment/APHIS-2021-0010-0003
https://downloads.regulations.gov/APHIS-2021-0010-0003/attachment_1.pdf
Chronic Wasting Disease CWD TSE PrP transmission to, Cattle, Sheep, Pigs, Cervid, Primates, oh my!
"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
Chronic wasting disease prions in cervids and wild pigs in North America Preliminary Outbreak Assessment DEFRA 26 January 2026
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.
https://assets.publishing.service.gov.uk/media/697a3b013c71d838df6bd413/CWD_Prions_in_Cervids_and_Wild_Pigs_in_North_America.pdf
https://transmissiblespongiformencephalopathy.blogspot.com/2026/01/chronic-wasting-disease-prions-in.html
https://prpsc.proboards.com/thread/201/defra-cervid-pigs-outbreak-assessment
Volume 31, Number 1—January 2025
Detection of Prions in Wild Pigs (Sus scrofa) from Areas with Reported Chronic Wasting Disease Cases, United States
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.
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
Experimental transmission of the chronic wasting disease agent to swine after oral or intracranial inoculation
Running Title: The chronic wasting disease agent transmits to swine
Discussion
snip...
In the case of feral pigs, exposure to the agent of CWD through scavenging of CWD-affected cervid carcasses or through consumption of prion contaminated plants or soil could allow feral pigs to serve as reservoirs of CWD infectivity. The range and numbers of feral pigs is predicted to continue to increase due to the ability of pigs to adapt to many climates, reproduce year-round, and survive on a varied diet (55 ). The range of CWD-affected cervids also continues to spread, increasing the likelihood of overlap of ranges of feral pigs and CWD -affected environments.
We demonstrate here that PrPSc accumulates in lymphoid tissues from pigs inoculated intracranially or orally with the CWD agent, and can be detected as early as 6 months after inoculation. Clinical disease suggestive of prion disease developed only in a single pig after a long (64 months) incubation period. This raises the possibility that CWD-infected pigs could shed prions into their environment long before they develop clinical disease. However, the low amounts of PrPSc detected in the study pigs combined with the low attack rates in Tg002 mice suggest that there is a relatively strong species barrier to CWD prions in pigs.
https://journals.asm.org/doi/10.1128/jvi.00926-17
Currently, swine rations in the U.S. could contain animal derived components including materials from deer or elk. In addition, feral swine could be exposed to infected carcasses in areas where CWD is present in wildlife populations. The current feed ban in the U.S. is based exclusively on keeping tissues from TSE infected cattle from entering animal feeds. These results indicating the susceptibility of pigs to CWD, coupled with the limitations of the current feed ban, indicates that a revision of the feed ban may be necessary to protect swine production and potentially human health.
The successful transmission of pig-passaged CWD to Tg40 mice reported here suggests that passage of the CWD agent through pigs results in a change of the transmission characteristics which reduces the transmission barrier of Tg40 mice to the CWD agent. If this biological behavior is recapitulated in the original host species, passage of the CWD agent through pigs could potentially lead to increased pathogenicity of the CWD agent in humans. Interestingly, bioassay of material from the longest surviving >6 month orally challenged pig (72 mpc), which was negative for PrPcwd by all other tests, produced a positive bioassay result. Bioassay of material from additional animals is currently underway. This study demonstrates that pigs can serve as potential hosts for CWD, although with low attack rates and scant PrPcwd accumulation. Detection of infectivity in orally challenged pigs using mouse bioassay raises the possibility that naturally exposed pigs act as a reservoir of CWD infectivity, even though affected pigs do not develop overt clinical signs or readily detectable PrPcwd.
https://www.ars.usda.gov/research/publications/publication/?seqNo115=326166
cwd scrapie pigs oral routes
***> However, at 51 months of incubation or greater, 5 animals were positive by one or more diagnostic methods. Furthermore, positive bioassay results were obtained from all inoculated groups (oral and intracranial; market weight and end of study) suggesting that swine are potential hosts for the agent of scrapie. <***
*** Although the current U.S. feed ban is based on keeping tissues from TSE infected cattle from contaminating animal feed, swine rations in the U.S. could contain animal derived components including materials from scrapie infected sheep and goats. These results indicating the susceptibility of pigs to sheep scrapie, coupled with the limitations of the current feed ban, indicates that a revision of the feed ban may be necessary to protect swine production and potentially human health. <***
***> Results: PrPSc was not detected by EIA and IHC in any RPLNs. All tonsils and MLNs were negative by IHC, though the MLN from one pig in the oral <6 month group was positive by EIA. PrPSc was detected by QuIC in at least one of the lymphoid tissues examined in 5/6 pigs in the intracranial <6 months group, 6/7 intracranial >6 months group, 5/6 pigs in the oral <6 months group, and 4/6 oral >6 months group. Overall, the MLN was positive in 14/19 (74%) of samples examined, the RPLN in 8/18 (44%), and the tonsil in 10/25 (40%).
***> 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=353091
https://www.ars.usda.gov/research/project/?accnNo=432011&fy=2017
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
Currently, swine rations in the U.S. could contain animal derived components including materials from deer or elk. In addition, feral swine could be exposed to infected carcasses in areas where CWD is present in wildlife populations. The current feed ban in the U.S. is based exclusively on keeping tissues from TSE infected cattle from entering animal feeds. These results indicating the susceptibility of pigs to CWD, coupled with the limitations of the current feed ban, indicates that a revision of the feed ban may be necessary to protect swine production and potentially human health.
https://www.ars.usda.gov/research/publications/publication/?seqNo115=353091
https://www.ars.usda.gov/research/project/?accnNo=432011&fy=2017
https://www.ars.usda.gov/research/publications/publication/?seqNo115=337105
https://www.ars.usda.gov/research/publications/publication/?seqNo115=326166
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
Component 6: Transmissible Spongiform Encephalopathies
Sheep scrapie agent can infect white-tailed deer after oronasal exposure.
The origin of chronic wasting disease (CWD) is not known, but it has many similarities to the sheep prion disease called scrapie. It has long been hypothesized that CWD arose through transmission of sheep scrapie to deer. ARS researchers in Ames, Iowa, conducted research to determine if scrapie derived from sheep could be transmitted to white-tailed deer. The deer inoculated with sheep scrapie developed clinical signs and the abnormal prion protein could be detected in a wide range of 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 suggests that it would be difficult to distinguish scrapie from CWD in deer or identify scrapie if a case occurs. This information should be considered by deer farmers for keeping their herds free from prion diseases.
https://www.ars.usda.gov/ARSUserFiles/np103/AnnualReports/NP103%20FY2023%20Annual%20Report_Final.pdf
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
***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
***> ”Our data suggest that the phenotype of CWD in sheep is indistinguishable from some strains of scrapie in sheep. Given our results, current detection techniques would be unlikely to distinguish CWD in sheep from scrapie in sheep if cross-species transmission occurred naturally.” https://pubmed.ncbi.nlm.nih.gov/34047228/
https://journals.sagepub.com/doi/full/10.1177/10406387211017615
SCRAPIE TSE Prion USA RAPID RESPONSE URGENT UPDATES DECEMBER 25, 2025
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
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
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
“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.”
Proceedings of the Prion 2025 - Advancing the understanding and treatment of prion diseases
ISBN: 978-65-80968-48-0
Identification of Camel Prion Disease in Tunisia: evidence of an emerging prion disease in North Africa
Amara, Abdelkader 1Bari, Michele Angelo Di 2Andolsi, Rihab 1Elmhatli, Kéfia 3Malek, Atef 1Bruno, Rosalia 4Chiappini, Barbara 5Vanni, Ilaria 6Esposito, Elena 5Riccardi, Geraldina 5Smida, Boubaker Ben 7Kessa, Haykel 8Chandoul, Walid 9Zrelli, Malek 10Abid, Obaid Allah Ben 5Marcon, Stefano 5Nonno, Romolo 5Agrimi, Umberto 5Vaccari, Gabriele 6Pirisinu, Laura 6 Vol 1, 2025 - 329818
Abstract Prion 2025
Abstract
Introduction: Camel prion disease (CPrD), a recently identified prion disease in dromedary camels from Algeria, has raised concerns regarding its potential spread in North Africa and possible implications for animal and public health.
Objectives: This study aimed to assess the presence of CPrD in Tunisia by investigating clinically suspect dromedary camels and characterizing the pathological and biochemical features of the disease.
Methods: Brain and lymph nodes from eight dromedary camels showing neurological and behavioral signs were sampled from the Tataouine and Sousse governorates. Samples were analysed by Western blot, immunohistochemistry, and histopathology techniques. PrP gene sequencing was also performed.
Results and Discussion: PrPSc accumulation was detected in six out of eight animals, with positivity confirmed in brain and, when available, lymph nodes. They showed molecular and neuropathological features closely resembling Algerian CPrD, clearly distinct from classical scrapie and BSE. All genotyped animals were homozygous for the wild-type PRNP allele. The detection of PrPSc in lymphoid organs, together with the relatively young age of some affected individuals, suggests the possibility of a contagious nature and early-life exposure.
Conclusion: This study provides the first identification of CPrD in Tunisia and underscores the importance of ongoing surveillance and the need to better understand the epidemiology, transmission dynamics, and zoonotic potential of this emerging prion disease.
Funding: This work was supported by grants: Bando Ricerca Indipendente ISS 2020-2022 (ID ISS20-97e1d82bda5a) by Istituto Superiore di Sanità; Bando “Dottorati di Ricerca Italia-Africa 2023” (DB04-id: 5165) by Università La Sapienza di Roma and Istituto Superiore di Sanità.
https://proceedings.science/prion-2025/papers?prod_proceedings_papers%5BrefinementList%5D%5Btrack.title.en%5D%5B0%5D=Animal%20prion%20diseases
Identification of Camel Prion Disease in Tunisia: evidence of an emerging prion disease in North Africa
The detection of PrPSc in lymphoid organs, together with the relatively young age of some affected individuals, suggests the possibility of a contagious nature and early-life exposure.
https://proceedings.science/prion-2025/papers?prod_proceedings_papers%5BrefinementList%5D%5Btrack.title.en%5D%5B0%5D=Animal%20prion%20diseases
https://camelusprp.blogspot.com/2026/02/
https://camelusprp.blogspot.com/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
APHIS USDA Captive CWD Herds Update by State December 2025 Update
CHRONIC WASTING DISEASE CASES
https://www.aphis.usda.gov/sites/default/files/status-of-captive-herds.pdf
APHIS USDA Captive CWD Herds Update by State December 2025 Update
https://chronic-wasting-disease.blogspot.com/2025/12/aphis-usda-captive-cwd-herds-update-by.html
https://prpsc.proboards.com/thread/187/aphis-captive-herds-update-december
Chronic Wasting Disease CWD TSE PrP transmission to, Cattle, Sheep, Pigs, Cervid, Primates, oh my!
Action Plan National Program 103 Animal Health 2022-2027
Component 6: Transmissible Spongiform Encephalopathies (TSEs)
Transmissible spongiform encephalopathies (TSEs) include several fatal diseases of people and animals involving degeneration of the nervous system and brain function. TSEs are caused by agents known as prions, or what appear to be primarily infectious proteins that cause normal protein (cellular-prion protein PrPc) molecules to convert into an abnormally structured form (disease-prion protein PrPsc) that can include inducement of the formation of proteinaceous deposits and plaques in the brain. TSEs include Creutzfeldt-Jakob disease (CJD), the primary human prion disease; Scrapie of sheep and goats; Chronic Wasting Disease (CWD) of deer, elk, and moose; and Bovine Spongiform Encephalopathy (BSE), also called “mad cow,” which is the cause of variant CJD (vCJD) in people and the only TSE known to have crossed the species barrier from animals to people.
Our understanding of TSEs continues to evolve with ongoing research efforts. TSEs are progressive but long developing diseases. In humans, for example, incubation periods from
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the time of contact with an infectious prion may be decades long. Consequently, completion of research plans in natural hosts may require several years. Improvements have been made with the development of experimental rodent models to shorten the time required to obtain experimental results, but the relevance of any findings in mouse models remains uncertain unless confirmed and validated in natural hosts. In 2004, the Institute of Medicine of the National Academies published a report entitled: Advancing Prion Science, Guidance for the National Prion Research Program. Several federal agencies have directed resources to implement recommendations in the report, including HHS-NIH, USDA-ARS, HHS-FDA, HHS-CDC, DoD, and EPA. Although significant scientific advances have been made, the research conducted to date has yet to deliver many of the concrete solutions needed to safeguard people and animals from these devastating diseases. A critical concern is the potential for environmental, genetic, or iatrogenic events to lead to new variant TSEs that are infectious and zoonotic.
The White House Office of Science and Technology Policy (OSTP) Interagency Working Group (IWG) on Prion Science identified the following research priorities to maximize the impact of the National Prion Research Program:
• Identification of the nature and origin of prion agents
• Studies on the pathobiology of prion strains
• Research on the determinants of transmissibility and epidemiology
• Development of diagnostics, detection, and surveillance
These interrelated priorities represent areas with critical gaps in our knowledge base. They were selected with the aim of establishing strategic collaborations that will produce benefits by aligning core competencies across Federal agencies. Especially notable are the potential benefits to be derived from collaboration between animal health and human-biomedical research.
All sectors that completed the 2020 ARS Animal Health Stakeholder Survey (government, academia, industry, and livestock and poultry producers) identified research on TSEs a national priority. Importantly, stakeholders identified the following TSEs as one of the 10 most important diseases that have the potential of significantly affecting animal agriculture in the United States: Chronic Wasting Disease (29%), Bovine Spongiform Encephalopathy (18%), and Scrapie (11%).
Producers that completed the 2020 ARS Animal Health Stakeholder Survey (beef, sheep, goats, and wildlife) also identified TSEs as one of the top five diseases currently affecting their commodity. The following TSEs were ranked by producers as one of the top five diseases, as follows:
Chronic Wasting Disease: Wildlife, including captive cervids (80%), sheep (15%), and beef (4.3%).
Bovine Spongiform Encephalopathy: Beef (8.7%).
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Scrapie: Sheep (56%), goats (17%), beef (4.3%).
Although recognized as important, ARS does not currently have resources to implement research for the following priority:
• Identification of the nature and origin of prion agents.
Problem Statement 6A: Determine pathobiology of prion strains
Important gaps remain in our basic understanding of the pathobiology of animal prion diseases. One critical need is understanding the tissue tropism and dissemination of prions and resolving the variations seen in different animal species. Proving especially problematic is that the normal prion protein is widely expressed, particularly on neurons in the brain, and is found on cell surfaces but its function is unclear. Another enigma of TSEs is that different strains are found within the same animal species. Importantly, there is evidence that atypical strains have emerged and there is a need to investigate the transmissibility of atypical Scrapie strains, such as the Nor98-like Scrapie.
Research Focus:
It is widely assumed that the oral route of infection is important in the pathogenesis of naturally occurring TSEs of livestock and cervids; however, basic research is needed to understand the mechanisms of transmission of TSE agents from the initial site of entry to the central nervous system. A notable feature of prion diseases is a lack of detectable immune responses and inflammation during the course of a prion infection, even though immune system cells may carry prions to target tissues. To date, research in animals suggests that prion accumulation may be largely influenced by the host species affected rather than the TSE involved. An investment in comparative pathology, which has not received much experimental attention, is needed to advance research programs in epidemiology and diagnostic discovery.
Anticipated Products:
• Scientific information on the mechanisms responsible for the development of multiple TSE strains within a host species.
• Scientific information on the manner in which prions enter the nervous system from peripheral sites of exposure such as a host’s gastrointestinal tract, nasal mucosa, skin, and eyes.
• Scientific information on the mechanisms by which prion spread within the nervous system.
• Scientific information on the mechanisms that control prion disease incubation times.
• Elucidate the mechanisms of prion neuropathogenesis.
• Determine prion distribution in goats infected with Scrapie.
• Scientific information on prion distribution in sheep infected with atypical Scrapie. Potential Benefits:
• Understanding the pathobiology of prion disease and tissue distribution in susceptible animal species is paramount to inform the development of detection methods and ability to develop countermeasures to protect against animal prion diseases.
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Problem Statement 6B: Reveal genetics of prion disease susceptibility
Prion diseases have stimulated intense scientific scrutiny since it was first proposed that the infectious agent was devoid of nucleic acid. Despite this finding, host genetics has played a key role in understanding the pathobiology and clinical aspects of prion diseases through the effects of a series of polymorphisms and mutations in the prion protein gene. The advent of vCJD confirmed a powerful human genetic susceptibility factor, as all patients with clinical disease have an identical genotype at the polymorphic codon 129 of the prion gene. The alternative variant at codon 129 is not protective, however, and abnormal prions have been found in lymphoid tissues of individuals of other prion genotypes after exposure to transfused blood products from patients who later succumbed to the disease. Familial forms of prion diseases are also known to be inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In most cases, an affected person inherits the altered gene from one affected parent. In some people, familial forms of prion disease are caused by a new mutation in the prion gene. Although such people most likely do not have an affected parent, they can pass the genetic change to their children. Familial Creutzfeldt-Jakob disease (fCJD), Gerstmann-Sträussler-Scheinker (GSS) syndrome, and fatal familial insomnia (FFI) represent the core phenotypes of genetic prion disease. Genetic studies in animals have uncovered similar polymorphisms and mutations in the prion protein gene. Genetic information has led to the discovery of genotypes with relative susceptibility and resistance to Scrapie in sheep. Current Scrapie control programs in the United States and Europe are based on the elimination of susceptible genotypes from the breeding pool. However, a significant portion of Scrapie resistance in sheep is not explained by the currently known resistance allele coding R, at codon 171, and codon A at codon 136. Less is known in cervids and CWD. In addition, recent evidence indicates that some forms of BSE may be genetic in nature. The 2006 U.S. H. -type atypical BSE cow had a polymorphism at codon 211 of the bovine prion gene, resulting in a glutamic acid to lysine substitution (E211K). This substitution is analogous to a human polymorphism associated with the most prevalent form of heritable TSE in humans, and it is considered to have caused BSE in 2006 in a U.S. case that was determined to be atypical BSE.
Research Focus:
The functional genomics of disease resistance are not completely understood, and recent research suggests genetic variations may lead to different clinical outcomes. There is a need to look more broadly at the genome of livestock species to identify markers associated with resistance to Scrapie in sheep and goats and CWD in cervids.
In the case of Scrapie, the sheep genome may help identify other alleles that may explain why some QR and RR sheep genotype are susceptible, allowing these sheep to be classified as susceptible and removed from the farm. This will make genotype testing a more effective control tool. This research area is aimed at utilizing powerful computational biology and bioinformatic approaches, along with traditional animal breeding experiments, to steadily improve our understanding of mechanisms of genetic disease resistance.
Our understanding of Scrapie genetic resistance in goats is not as advanced as sheep Scrapie, and there is a need to identify markers for genetic resistance in goats. This will enable the use
40
of markers identified to develop resistant lines of high production meat and milk goats in cooperation with industry. The USDA eradication program is increasing its focus on goats and it is critically important to provide other options to goat producers besides whole herd depopulation, with the hope that premises contamination does not result in reinfection. Scrapie eradication in the United States will not be achieved unless it is eradicated from sheep and goats.
Anticipated Products:
• Identification of genetic variations associated with disease susceptibility.
• Scientific information on the correlation between host genotypes and the phenotypes of prion agents.
• Identification of genetic factors controlling susceptibility of goats to Scrapie. • Scientific information to evaluate the effectiveness of disease resistance breeding programs in sheep.
• Scientific information to evaluate sheep ARR/ARR genotype for resistance to different TSE strains.
• Determine whole genome associations with TSE susceptibility or resistance in sheep, goats, and cervids.
• Determine the effects of the PRNP genotype on current diagnostic test assay accuracy in sheep and goats with Scrapie.
Potential Benefits:
• The identification of genetic markers associated with disease susceptibility and resistance.
• Ability to develop prion disease control programs by selecting farm animals that are resistant to prion diseases.
• Ability to enhance surveillance programs for animals known to be genetically susceptible to prion diseases.
Problem Statement 6C: Diagnose, detect, and prevent prion diseases
Important gaps remain in our arsenal of diagnostic tools for early detection and countermeasures to prevent disease outbreaks, transmission, and spread. Current diagnostic tests were validated for use only on post-mortem samples; simple, sensitive, cost-effective ante mortem tests have yet to be developed. Because there is no detectable immune response or inflammation during the course of TSE infection, direct tests are needed to confirm a diagnosis. At present, only highly infected tissues, such as brain material or lymph tissue, are suitable for providing accurate diagnosis.
There is also a need to determine what level of environmental contamination can lead to infections in animals, and then develop a test for determining if this level of contamination exists on farm premises.
Significant gaps also remain for inactivating TSEs in farm settings. Currently the methods available for prion inactivation are not very effective in soil and other organic material. This is problematic as most contaminated bedding is either buried, left as is, or tilled in the soil relying on exclusion or dilution. Research studies have shown that prions last a very long
41
time when bound to soils or water and may be taken up by plants. Development of a cost- effective method of prion inactivation to non-transmissible levels is needed.
Research Focus:
Diagnostic approaches currently in use include techniques such as immunohistochemistry (IHC), Western blot, and enzyme-linked immunosorbent assays (ELISA). IHC is one of the original tests developed and is considered the gold standard, but it is more labor intensive and time consuming than the other two, whereas the Western blot and particularly ELISA tests are more efficient for the initial screening of large numbers of samples. Another method is the Conformation-Dependent Immunoassay (CDI), currently a research technique that claims to discriminate between normal prion and the abnormal prion on the basis of its shape, but this has yet to be validated as a diagnostic test in animals. New technologies and methods have been described using protein misfolding cyclic amplification techniques (PMCA), similar in concept to gene/DNA amplification, which effectively increases the concentration of prions in normal or pathological conformations. There is a critical need to improve diagnostics methods for surveillance, including the discovery of an ante mortem test for early detection and implementation of intervention strategies. There is also a critical need to develop tools for inactivating TSEs in farm settings, especially the inactivation of TSEs present in organic material.
Anticipated Products:
• TSE diagnostic test capable of detecting low levels of abnormal prions (i.e., key step to enable the development of an ante mortem test that can identify disease during the early stages of incubation).
• Improved live animal and post mortem tests for Scrapie.
• Develop a sensitive, high-throughput assay suitable for use in veterinary diagnostic laboratories for detection of PrP-Sc in sheep with classical scrapie.
• Develop a live animal test for the early detection of CWD in white tail deer.
• Validation of existing biopsy-based TSE tests in goats, deer, and elk.
• Standardize sampling and assay protocols for screening environments for CWD and Scrapie prions.
• Rapid biochemical methods for strain typing.
• Determine the suitability of a sensitive, high-throughput assay for detection of PrP-Sc (Nor98) in brain, peripheral tissues, and placentas from Sheep with Nor98.
• Validated murine models for strain typing.
• Improved diagnostics for TSEs in bodily fluids, including blood and other readily available samples in host species.
• Technologies to distinguish infectious prions from normal cellular prion proteins.
• A sensitive, high-throughput assay suitable for use in veterinary diagnostic laboratories for detection of PrP-Sc in sheep with classical scrapie.
• Effective chemicals with anti-prion properties that can safely be used in farm environments.
Potential Benefits:
• Effective surveillance programs based on early detection of animal prion diseases.
• Deployment of animal prion disease prevention measures.
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Component 6 Resources:
The following ARS locations have research projects addressing the problem statements identified under Component 7:
• Albany, California
• Ames, Iowa
• Pullman, Washington
snip…
https://www.ars.usda.gov/ARSUserFiles/np103/Action%20Plan%20-%20Animal%20Health%202022-2027_final.pdf
Animal Health (NP103) Annual Report for 2024
Component 6: Transmissible Spongiform Encephalopathies (TSEs)
Problem Statement 6A: Determine pathobiology of prion strains.
The naturally occurring lysine to glutamic acid substitution (E211K in the bovine prion protein) results in short incubation periods for H-type bovine spongioform encephalopathy (BSE).
Virus and Prion Research Unit, National Animal Disease Center, Ames, Iowa Classical BSE (C-BSE) is a prion disease of cattle that was responsible for the “mad cow disease” epizootic in Europe in the 1980s. C-BSE was determined to cause the human prion disease vCJD. Since then, atypical spontaneous strains of BSE were identified. H-BSE is one of those strains. Much research has explored the origins of C-BSE, and strain emergence from atypical H-BSE is one hypothesis. An H-BSE case was determined to have a germline mutation, an E211K substitution in the prion protein gene, which is analogous to a hereditary human prion disease. ARS scientists in Ames, Iowa reported the transmission of H-BSE from cattle, with and without the germline prion protein amino acid substitution, to cattle with various prion genotypes: EE211 (wild-type), EK211, and KK211. Results indicated a significantly shorter incubation period in K containing cattle compared to prion wild-type cattle. The scientists also explored the possibility that the C-BSE strain might have occurred after serial passages of EK211 and KK211 containing H-BSE in cattle, but results did not support this concept. This information is important to prion researchers, veterinary diagnostic laboratories, and those involved with establishing regulatory guidelines.
Problem Statement 6B: Reveal genetics of prion disease susceptibility.
Greater frequency of chronic wasting disease in free-ranging elk genetically tolerant to disease progression raises concerns related to prion transmission and strain evolution.
Animal Disease Research Unit, Pullman, Washington
Genetic variations in the prion protein gene of Rocky Mountain elk do not confer complete resistance to fatal infection by chronic wasting disease. However, elk carrying one or two copies of the amino acid leucine (L) variant at position 132 of the prion protein (132L*, where * is either M for methionine or L) survive much longer than 132MM elk. An ARS researcher in Pullman, Washington, in collaboration with researchers at the University of Wyoming, the University of California at Davis, the National Park Service, and the Animal and Plant Health Inspection Service, found a higher frequency of 132L* elk in areas of Wyoming with high infection rates, consistent with the expected positive effect of prolonged survival on reproduction. However, the frequency of chronic wasting disease infection in 132L* elk was also higher than previous estimates. To improve the long-term management of native elk populations, these findings underscore the importance of determining the effects of prolonged infection on disease transmission from 132L* elk and the potential for driving prion strain diversification.
https://www.ars.usda.gov/ARSUserFiles/np103/AnnualReports/Final%20NP103%20FY2024%20Annual%20Report.updated%205.30.25.pdf
USA BSE TSE PrP
Six of the seven cases of BSE identified in the United States have been diagnosed as atypical BSE. In most cases, the animals were 10 years of age or older. Two of the six detections of atypical BSE involved animals aged approximately 5 years or older.
https://www.aphis.usda.gov/sites/default/files/fs-bse.pdf
USA BSE Testing and Surveillance?
Bottom line, USA is testing so few cows for BSE (<25k tested annually)
https://www.aphis.usda.gov/livestock-poultry-disease/cattle/bse/bse-surveillance-program
BUT, even at those low testing figures, the USA did just confirm another case of BSE just here recently. Feed ban has failed terribly, and CWD is spreading in the USA, at an alarming rate. Recent transmission studies show oral transmission of CWD of Cervid to cattle. Studies also show links of sporadic CJD to BSE, Scrapie, and CWD. It’s a Whole new game of Prion poker now$$$
Wednesday, May 24, 2023
***> WAHIS, WOAH, OIE, United States of America Bovine spongiform encephalopathy Immediate notification
https://wahis.woah.org/#/in-review/5067
https://woahoie.blogspot.com/2023/05/wahis-woah-oie-united-states-of-america.html
https://prpsc.proboards.com/thread/125/wahis-woah-oie-immediate-notification
SATURDAY, MAY 20, 2023
***> Tennessee State Veterinarian Alerts Cattle Owners to Disease Detection Mad Cow atypical L-Type BSE
https://bse-atypical.blogspot.com/2023/05/tennessee-state-veterinarian-alerts.html
https://prpsc.proboards.com/thread/123/tennessee-veterinarian-alerts-cattle-confirmed
MAY 19, 2023
https://www.aphis.usda.gov/aphis/newsroom/stakeholder-info/sa_by_date/sa-2023/bse
2 weeks before the announcement of this recent mad cow case in the USA, i submitted this to the APHIS et al;
***> APPRX. 2 weeks before the recent mad cow case was confirmed in the USA, in Tennessee, atypical L-Type BSE, I submitted this to the APHIS et al;
Document APHIS-2023-0027-0001 BSE Singeltary Comment Submission May 2, 2023
''said 'burden' cost, will be a heavy burden to bear, if we fail with Bovine Spongiform Encephalopathy BSE TSE Prion disease, that is why this information collection is so critical''...
https://www.regulations.gov/comment/APHIS-2023-0027-0002
https://downloads.regulations.gov/APHIS-2023-0027-0002/attachment_1.pdf
Bovine Spongiform Encephalopathy BSE TSE Prion Origin USA?, what if?
Research Project: Pathobiology, Genetics, and Detection of Transmissible Spongiform Encephalopathies Location: Virus and Prion Research
Title: Sheep are susceptible to the agent of TME by intracranial inoculation and have evidence of infectivity in lymphoid tissues
Author item CASSMANN, ERIC - Oak Ridge Institute For Science And Education (ORISE) item MOORE, SARA - Oak Ridge Institute For Science And Education (ORISE) item SMITH, JODI - Iowa State University item Greenlee, Justin
Submitted to: Frontiers in Veterinary Science Publication Type: Peer Reviewed Journal Publication Acceptance Date: 11/14/2019 Publication Date: 11/29/2019 Citation: Cassmann, E.D., Moore, S.J., Smith, J.D., Greenlee, J.J. 2019.
Sheep are susceptible to the agent of TME by intracranial inoculation and have evidence of infectivity in lymphoid tissues.
Frontiers in Veterinary Science. 6:430. https://doi.org/10.3389/fvets.2019.00430. DOI: https://doi.org/10.3389/fvets.2019.00430
Interpretive Summary: Prion diseases are protein misfolding diseases that are transmissible between animals. The outcome of prion infection is irreversible brain damage and death. Transmission can occur between animals of the same or different species, however, transmission between different species is usually less efficient due to the species barrier, which results from differences in the amino acid sequence of the prion protein between the donor and recipient species. The present work evaluated whether transmissible mink encephalopathy (TME) can infect sheep. Our results demonstrate that sheep are susceptible to the TME agent and that the TME agent has similar properties to the agent of L-type atypical bovine spongiform encephalopathy (L-BSE). This work supports the ideas that L-BSE is a possible source for TME in mink and that the practice of feeding cattle with neurologic disease to mink should be avoided. This information is important to farmers who raise cattle, sheep, or mink.
Technical Abstract: Transmissible mink encephalopathy (TME) is a food borne prion disease. Epidemiological and experimental evidence suggests similarities between the agent of TME and L-BSE. This experiment demonstrates the susceptibility of four different genotypes of sheep to the agent of TME by intracranial inoculation. The four genotypes of sheep used in this experiment had polymorphisms corresponding to codons 136 and 171 of the prion gene: VV136QQ171, AV136QQ171, AA136QQ171, and AA136QR171. All intracranially inoculated sheep without comorbidities (15/15) developed clinical scrapie and had detectable PrPSc by immunohistochemistry, western blot, and enzyme immunoassay (EIA). The mean incubation periods in TME infected sheep correlated with their relative genotypic susceptibility. There was peripheral distribution of PrPSc in the trigeminal ganglion and neuromuscular spindles; however, unlike classical scrapie and C-BSE in sheep, ovine TME did not accumulate in the lymphoid tissue. To rule out the presence of infectious, but proteinase K susceptible PrPSc, the lymph nodes of two sheep genotypes, VV136QQ171 and AA136QQ171, were bioassayed in transgenic ovinized mice. None of the mice (0/32) inoculated by the intraperitoneal route had detectable PrPSc by EIA. Interestingly, mice intracranially inoculated with RPLN tissue from a VV136QQ171 sheep were EIA positive (3/17) indicating that sheep inoculated with TME harbor infectivity in their lymph nodes. Western blot analysis demonstrated similarities in the migration patterns between ovine TME and the bovine TME inoculum. Overall, these results demonstrate that sheep are susceptible to the agent of TME, and that the tissue distribution of PrPSc in TME infected sheep is distinct from classical scrapie.
https://www.ars.usda.gov/research/publications/publication/?seqNo115=363305
https://www.ars.usda.gov/research/publications/publication/?seqNo115=360665
https://www.ars.usda.gov/research/publications/publication/?seqNo115=373668
Previous work has shown that the Stetsonville, WI outbreak of TME could have been precipitated by feeding mink a downer cow with atypical BSE; therefore, it very well may have originated from a cow with L-BSE. The agent of TME appears to remain stable, and it has a high transmission efficiency after a sequence of interspecies transmission events. Although C-BSE is the archetypal foodborne TSE, our findings indicate that L-BSE and bTME have greater transmission efficiencies in bovinized mice. Previous work has demonstrated that L-BSE also is more virulent than C-BSE in mice expressing the human prion protein [46, 55]. Although the documented incidence of L-BSE is low, the propensity of L-BSE and the TME agent to cross species barriers support the continued monitoring for atypical BSE.
https://bmcvetres.biomedcentral.com/articles/10.1186/s12917-020-02611-0
***>This work supports the ideas that L-BSE is a possible source for TME in mink and that the practice of feeding cattle with neurologic disease to mink should be avoided. This information is important to farmers who raise cattle, sheep, or mink.<***
1985
Evidence That Transmissible Mink Encephalopathy Results from Feeding Infected Cattle Over the next 8-10 weeks, approximately 40% of all the adult mink on the farm died from TME.
snip...
The rancher was a ''dead stock'' feeder using mostly (>95%) downer or dead dairy cattle...
https://web.archive.org/web/20090506002258/http://www.bseinquiry.gov.uk/files/mb/m09/tab05.pdf
https://web.archive.org/web/20090506001031/http://www.bseinquiry.gov.uk/files/mb/m09a/tab01.pdf
https://web.archive.org/web/20090506024922/http://www.bseinquiry.gov.uk/files/yb/1987/06/10004001.pdf
Re-USA BSE Surveillance, BSE Testing, BSE Feed Regulation (21 CFR 589.2000), SRMs, and CWD
“Conclusion: These results demonstrate the oral transmission potential of atypical BSE in cattle. Surprisingly, regardless of which atypical type of BSE was used for P1 oral challenge, Prpsc in the P2 animals acquired biochemical characteristics similar to that of Prps in C-BSE, suggesting atypical BSE as a possible origin of C-BSE in UK.”
Abstract for Prion 2023
Title: Transmission of atypical BSE: a possible origin of Classical BSE in cattle
Abstract for Prion 2023
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
Problem Statement 6B: Reveal genetics of prion disease susceptibility.
Greater frequency of chronic wasting disease in free-ranging elk genetically tolerant to disease progression raises concerns related to prion transmission and strain evolution.
Animal Disease Research Unit, Pullman, Washington
Genetic variations in the prion protein gene of Rocky Mountain elk do not confer complete resistance to fatal infection by chronic wasting disease. However, elk carrying one or two copies of the amino acid leucine (L) variant at position 132 of the prion protein (132L*, where * is either M for methionine or L) survive much longer than 132MM elk. An ARS researcher in Pullman, Washington, in collaboration with researchers at the University of Wyoming, the University of California at Davis, the National Park Service, and the Animal and Plant Health Inspection Service, found a higher frequency of 132L* elk in areas of Wyoming with high infection rates, consistent with the expected positive effect of prolonged survival on reproduction. However, the frequency of chronic wasting disease infection in 132L* elk was also higher than previous estimates. To improve the long-term management of native elk populations, these findings underscore the importance of determining the effects of prolonged infection on disease transmission from 132L* elk and the potential for driving prion strain diversification.
https://www.ars.usda.gov/ARSUserFiles/np103/AnnualReports/Final%20NP103%20FY2024%20Annual%20Report.updated%205.30.25.pdf
https://www.ars.usda.gov/animal-production-and-protection/animal-health/docs/annual-reports/
Research Project: Elucidating the Pathobiology and Transmission of Transmissible Spongiform Encephalopathies
Location: Virus and Prion Research
Title: Update: CWD genetic resistance project at NADC
Author item Cassmann, Eric item Greenlee, Justin Submitted to: North American Deer Farmer Publication Type: Trade Journal Publication Acceptance Date: 11/5/2023 Publication Date: 11/15/2023 Citation: Cassmann, E.D., Greenlee, J.J. 2023.
Update: CWD genetic resistance project at NADC. North American Deer Farmer. P. 83.
Interpretive Summary: Technical Abstract:
In March of 2020, we began a study to examine the susceptibility of whitetail deer with rare prion protein genotypes to chronic wasting disease (CWD). In the sequence of amino acids that make up the deer prion protein, there are several locations that are variable. These variations are sometimes called polymorphisms. In the data collected from depopulations, whitetail deer with certain prion gene polymorphisms were not positive for CWD. In 2019, Dr. Nick Haley published a paper that showed H95/S96, HH95, and S96/K226 deer from depopulated herds in the US were not CWD positive. Based on the overall low number of deer with these genotypes () we’re unable to determine if they were resistant to CWD or if there were too few deer with these genotypes to be statistically represented in the positive cases. It’s also possible that they could be partially susceptible with longer incubation times than deer with generic (wild type) prion genotypes. Samples gathered at depopulation represent a snapshot of the herd. It is possible these rare genotypes were exposed, but had not yet accumulated abnormal prion protein to a level detectable by the detection methods used. The NADC susceptibility study was initiated to help answer these questions.
We studied deer with polymorphisms at 3 amino acid locations (codons): 95, 96, and 226. Wild type deer are QQ95GG96QQ226. Whitetail deer with wild type prion genotypes were inoculated with CWD and co-housed with other whitetail deer (contact deer) that had rare prion protein genotypes. The genotypes of contact deer included QH95GS96QQ226, QH95GG96QK226, QQ95GS96QQ226, QQ95SS96QQ226, Q95GS96QK226, and QQ95GG96KK226 (bolded text indicates a prion gene polymorphism). During the first year, we collected feces, saliva, nasal swabs, skin, blood, and rectal biopsies from the inoculated and contact deer to determine if deer are CWD positive and the period of CWD shedding. After the first year, we started collecting rectal biopsies annually on the contact deer, but all other samples are still collected every three months.
Eight out of ten (8/10) inoculated deer developed clinical signs for CWD and tested positive after necropsy (Figure 1). The average time from inoculation to euthanasia of these eight inoculated deer was 23 months. Two inoculated deer are still on-study; one of these deer has tested positive for CWD on rectal biopsy IHC.
To date, two deer from the contact group have developed CWD clinical signs and tested positive (Figure 2). The positive deer from the contact group had the GS96QK226 and KK226 genotypes.
We have detected CWD prions in rectal biopsies with IHC in three other contact deer as of October 2023. Their prion genotypes are GS96, QH95GS96, and GS96QK226.
As the experiment continues, we hope to answer 2 main questions. (
1) Are there any prion protein polymorphisms that make deer resistant to CWD, and
(2) what are the CWD shedding dynamics in deer with detectable CWD.
One potential outcome of the study would be identifying genotypes with very long incubation periods that, while susceptible to CWD, still could be used to manage CWD.
https://www.ars.usda.gov/research/publications/publication/?seqNo115=410188
Update: CWD genetic resistance project at NADC 1) Are there any prion protein polymorphisms that make deer resistant to CWD, and (2) what are the CWD shedding dynamics in deer with detectable CWD. One potential outcome of the study would be identifying genotypes with very long incubation periods that, while susceptible to CWD, still could be used to manage CWD.
https://www.ars.usda.gov/research/publications/publication/?seqNo115=410188
''There are no known familial or genetic TSEs of animals, although polymorphisms in the PRNP gene of some species (sheep for example) may influence the length of the incubation period and occurrence of disease.''
c) The commonest form of CJD occurs as a sporadic disease, the cause of which is unknown, although genetic factors (particularly the codon 129 polymorphism in the prion protein gene (PRNP)) influence disease susceptibility. The familial forms of human TSEs (see Box 1) appear to have a solely genetic origin and are closely associated with mutations or insertions in the PRNP gene. Most, but not all, of the familial forms of human TSEs have been transmitted experimentally to animals. There are no known familial or genetic TSEs of animals, although polymorphisms in the PRNP gene of some species (sheep for example) may influence the length of the incubation period and occurrence of disease.
https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/209755/Part_1_-_Introduction.pdf
P-145 Estimating chronic wasting disease resistance in cervids using real time quaking- induced conversion
Nicholas J Haley1, Rachel Rielinqer2, Kristen A Davenport3, W. David Walter4, Katherine I O'Rourke5, Gordon Mitchell6, Juergen A Richt2 1
Our studies demonstrate that in vitro amplification metrics predict in vivo susceptibility, and that alleles with multiple codons, each influencing resistance independently, do not necessarily contribute additively to resistance. Importantly, we found that the white-tailed deer 226K substrate exhibited the slowest amplification rate among those evaluated, suggesting that further investigation of this allele and its resistance in vivo are warranted to determine if absolute resistance to CWD is possible. ***at present, no cervid PrP allele conferring absolute resistance to prion infection has been identified.
PRION 2016 CONFERENCE TOKYO
http://prion2016.org/dl/newsletter_03.pdf
http://chronic-wasting-disease.blogspot.com/2017/04/
***> at present, no PrPC allele conferring absolute resistance in cervids has been identified.
J Gen Virol. 2017 Nov; 98(11): 2882–2892.
Published online 2017 Oct 23. doi: 10.1099/jgv.0.000952
Estimating chronic wasting disease susceptibility in cervids using real-time quaking-induced conversion
Chronic wasting disease (CWD) resistance in cervids is often characterized as decreased prevalence and/or protracted disease progression in individuals with specific alleles; at present, no PrPC allele conferring absolute resistance in cervids has been identified.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5845664/pdf/jgv-98-2882.pdf
Another potential and likely outcome of this study, imo, is that genotypes developed with very long incubation, could therefore, if released into the wild, could help spread cwd even further, exposing even more wild species, and surrounding environments, for even longer periods of time, due to the longer incubation, a terrible potential outcome, one that must be avoided at all cost, imo…terry
Chronic Wasting Disease CWD TSE PrP transmission to, Cattle, Sheep, Pigs, Cervid, Primates, oh my!
ARS Research Elucidating the Pathobiology and Transmission of Transmissible Spongiform Encephalopathies 2025 Annual Report
Chronic Wasting Disease CWD TSE PrP transmission to, Cattle, Sheep, Pigs, Cervid, Primates, oh my!
Price of TSE Prion Poker Goes Up Again…terry
https://transmissiblespongiformencephalopathy.blogspot.com/2025/12/ars-research-elucidating-pathobiology.html
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
***> 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
TUESDAY, SEPTEMBER 30, 2025
USDA EXPLANATORY NOTES ANIMAL AND PLANT HEALTH INSPECTION SERVICE 2025-2014 CHRONIC WASTING DISEASE CWD TSE CERVID
https://chronic-wasting-disease.blogspot.com/2025/09/usda-explanatory-notes-animal-and-plant.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
TUESDAY, SEPTEMBER 30, 2025
USDA National Scrapie Program History and Bovine Spongiform Encephalopathy BSE TSE Update 2025
https://scrapie-usa.blogspot.com/2025/09/usda-national-scrapie-program-history.html
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
***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
***> ”Our data suggest that the phenotype of CWD in sheep is indistinguishable from some strains of scrapie in sheep. Given our results, current detection techniques would be unlikely to distinguish CWD in sheep from scrapie in sheep if cross-species transmission occurred naturally.”
https://pubmed.ncbi.nlm.nih.gov/34047228/
https://journals.sagepub.com/doi/full/10.1177/10406387211017615
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
Volume 31, Number 12—December 2025
Research
Oral Transmission of Classical Bovine Spongiform Encephalopathy in ARR/ARR Sheep
Alvina Huor1, Frederic Lantier1, Jean-Yves Douet, Severine Lugan, Naima Aron, Chloe Mesic, Herve Cassard, Tomás Barrio, Hugh Simmons, Isabelle Lantier, and Olivier Andreoletti
Comments to Author Author affiliation: University of Toulouse, Toulouse, France (A. Huor, J.-Y. Douet, S. Lugan, N. Aron, C. Mesic, H. Cassard, T. Barrio, O. Andreoletti); National Research Institute for Agriculture, Food and Environment, Nouzilly, France (F. Lantier, I. Lantier); Animal and Plant Health Agency, Weybridge, UK (H. Simmons)
Abstract
Selection for the A136R154R171 PRNP allele is known to curb classical scrapie in sheep, and we expected it to minimize the risk for classical bovine spongiform encephalopathy (c-BSE) propagation. We orally challenged newborn ARR/ARR and ARQ/ARQ lambs with ovine-passaged c-BSE. Contrary to our expectations, prion disease developed in all ARR/ARR lambs after markedly longer incubation times (≈50 months) than ARQ/ARQ controls (≈20 months). Tissue distribution of the abnormal isoform of prion protein (PrP) in clinically affected ARR/ARR sheep largely mirrored tissue distribution seen in ARQ/ARQ animals. Bioassays in bovine- and human-PrP transgenic mice showed that passage through ARR/ARR sheep did not increase the agent’s zoonotic potential. Transmission efficiency in human normal cellular isoform PrP-expressing mice remained similar to cattle c-BSE and lower than ARQ-passaged c-BSE. Our data reveal the limitations of breeding exclusively for ARR when the objective is to mitigate c-BSE risk and underscore the need to maintain specific-risk-material removal and surveillance programs.
Prion diseases, or transmissible spongiform encephalopathies (TSE), are fatal neurodegenerative disorders that occur naturally in various mammalian species, including sheep (scrapie), cervids (chronic wasting disease), and humans (Creutzfeldt-Jakob disease [CJD]). A key event in the pathogenesis of TSEs is the conversion of the normal cellular prion protein (PrPC), encoded by the PRNP gene, into an abnormal disease-associated isoform (PrPSc) within the tissues of those affected. PrPC is completely degraded after controlled digestion with proteinase K (PK) under nondenaturing conditions, whereas PrPSc is N terminally truncated under such conditions, leaving a PK-resistant core termed PrPres (1).
In 1985, classical bovine spongiform encephalopathy (c-BSE), a new prion disease affecting cattle, was identified in the United Kingdom (2). The number of c-BSE cases in cattle rapidly increased because of the recycling of infected carcasses into the feed chain in the form of meat and bone meal (MBM) (3). Over the next 2 decades, c-BSE disseminated to >28 countries, mostly in Europe but also in the United States, Canada, and Japan, through the export of infected live animals and contaminated MBM and livestock feed.
Experimental oral or parenteral exposure to c-BSE demonstrated its transmissibility to sheep (4). Because MBM was also distributed to small ruminants, the potential spread of c-BSE in the sheep population became a major concern for health authorities. The emergence of variant CJD (vCJD) in humans, because of dietary exposure to the c-BSE agent, further reinforced those concerns, making the prevention of any potential spread of c-BSE to small ruminants a top priority in Europe (5,6).
In sheep, susceptibility to prion diseases is determined principally by polymorphisms in the PRNP gene. The major polymorphic sites influencing susceptibility to classical scrapie are located at codons 136 (A or V), 154 (R or H), and 171 (R, Q, or H) (7,8), which also strongly influence susceptibility to BSE. Sheep with the AHQ/AHQ and ARQ/ARQ PrP genotypes are highly susceptible to c-BSE infection when exposed through intracerebral or oral routes (4).
In contrast, intracerebral inoculation of ARR/ARR sheep with cattle c-BSE resulted in an inefficient transmission of the disease (incomplete attack rate), and oral inoculation failed to transmit disease or cause detectable accumulation of prion infectivity or abnormal PrP in the peripheral tissues or central nervous system (9). Those findings led to the conclusion that the ARR/ARR PrP genotype confers strong, if not complete, resistance to c-BSE infection in sheep. Selection for the ARR allele was originally conceived as a tool to control classical scrapie in farmed sheep population, but it also appeared to protect against possible c-BSE transmission (10). In this study, we experimentally exposed ARQ/ARQ and ARR/ARR newborn lambs orally to c-BSE passaged in ARQ/ARQ sheep to determine transmission efficiency of the disease.
snip…
Discussion
The efficient transmissions observed in orally challenged ARR/ARR animals demonstrate that this genotype does not provide substantial resistance against the ovine c-BSE agent. Our results strongly contrast with those previously obtained in ARR/ARR and ARR/ARQ sheep orally challenged with cattle c-BSE, where no clinical signs and no or limited PrPSc accumulation has been evidenced, whereas positive transmission occurred in ARQ/ARQ sheep (22–24).
The inoculation doses used in this study (5 g of brain equivalent material) were similar to those used in studies that concluded the absence of cattle c-BSE transmission through the oral route in ARR/ARR sheep. However, in the absence of an endpoint titration establishing the c-BSE titer in our inoculum, the hypothesis that differences in the infectious titer in the inoculum account for, or at least contribute to, the discrepancies observed between studies cannot be ruled out.
In sheep, the age at the time of inoculation does appear to affect the efficacy of c-BSE transmission in orally exposed ARQ/ARQ sheep (25). Transmission efficiency is much higher in animals challenged before weaning (<3 weeks) than in animals inoculated after weaning (>3 months). In our study, lambs were orally challenged 24 hours after birth and at the age of 2 weeks, whereas in previous studies, where no c-BSE transmission to ARR/ARR animals was observed, the age at inoculation varied from 3–6 months (26,27) or 5–8 months (22).
Experimental oral exposure early after birth is potentially more relevant to a scenario where maternal lateral transmission (via milk and contact with placenta) would play a central role in the disease transmission, as observed in classical scrapie–infected flocks (28,29). Experimental oral challenge after weaning is certainly a relevant model to mimic a scenario where sheep would be exposed to the c-BSE agent through the ingestion of contaminated feedstuffs (meat and bone meal), as observed in cattle during the c-BSE epidemics.
The last major difference between our transmission experiment and those reported in previous studies was the use of an ovine-adapted c-BSE rather than cattle c-BSE as inoculum. The apparent higher capacity of ARQ/ARQ sheep-passaged c-BSE (when compared with cattle c-BSE) to cross transmission barriers (transmission to porcine and human PrP-expressing hosts) is a well-documented phenomenon. The use of such ovine-passaged c-BSE as inoculum could, at least partly, explain the efficient transmission of the c-BSE agent to ARR/ARR sheep.
During the past 20 years, a breeding for resistance policy relying on the progressive increase of the ARR allele frequency in sheep has been implemented by certain member states of the European Union (EU). That policy’s original objectives were to reduce the global incidence of TSEs and to prevent c-BSE emergence and spread in sheep populations. The most recent analysis of the small ruminants’ TSE epidemiologic situation in the EU confirmed that the breeding for resistance policy is an efficient means to reduce classical scrapie prevalence in sheep populations (10). However, the transmission of the c-BSE agent to ARR/ARR sheep reported in this study suggests that ARR allele selection could have a more limited effect than originally expected on the risk for c-BSE propagation in the sheep population.
At the clinical stage of the disease, the distribution and levels of c-BSE prions in the peripheral tissues of both ARR/ARR and ARQ/ARQ experimentally challenged animals were broadly similar. The main differences observed between both genotypes were a slower dissemination of the c-BSE agent in the organism and a longer incubation period in the ARR/ARR animals.
In the humanized transgenic mouse panel, both ARR/ARR- and ARQ/ARQ-derived c-BSE remained transmissible to mice expressing methionine 129 human PrPC, confirming that neither ovine genotype eliminates zoonotic potential. However, the ARR/ARR isolate exhibited modestly reduced transmission efficiency, evident as a lower primary attack rate and longer mean survival times, compared with its ARQ/ARQ counterpart. Those kinetic differences were largely lost after a single adaptation passage, however, suggesting that once the species barrier is crossed, the underlying strain behaves similarly.
In 2001, specific risk material (SRM) measures were implemented throughout the EU, consisting of the systematic removal of cattle and small ruminants’ tissues susceptible to contain critical levels of prion infectivity from the food and feed chains. The SRM measures are key for ensuring the protection of consumers against exposure to prions present in farmed animals. Current SRM measures applied to small ruminants in the EU consist of the removal of the spleen and the ileum and, in animals over 12 months of age, the skull (including the eyes and brain), spinal cord, and tonsils. Because of the large distribution of TSE infectivity in the lymphoid tissues of small ruminants, SRM measures applied to sheep and goats are considered to have a more limited effect on the protection of consumers than they have in the cattle c-BSE context (30). However, mathematical modeling of the effect of the SRM measures on the different prion diseases susceptible to occur in small ruminants (atypical scrapie, classical scrapie, and c-BSE) confirmed the strong positive effect of the SRM measures on the final consumer exposure to these different prions (31).
In conclusion, although the capacity of the c-BSE agent to propagate in ARR/ARR sheep can be considered unfortunate news, the continuation of the TSE surveillance and SRM measures currently in force for small ruminants in the EU will continue to ensure efficient protection against the risk for exposure to this zoonotic agent. c-BSE infection in ARR/ARR sheep can still pose a public-health risk, but the quantitative probability of successful cross-species transmission might be lower than transmission associated with ARQ/ARQ sheep cases.
Dr. Huor is an assistant engineer in the transmissible spongiform encephalopathies research group at the University of Toulouse. Her primary research interests are the pathogenesis of prion diseases and the evolution of prion strain properties, with special emphasis on their iatrogenic and zoonotic risks of transmission.
Acknowledgment
This work was supported by the European Union (grant no. QLK-CT 2001-309, program nos. FEDER/INTERREG EFA282/13 TRANSPRION, EFA148/16 REDPRION, and EFA031/01 NEUROCOOP).
References
https://wwwnc.cdc.gov/eid/article/31/12/25-0501_article
Volume 31, Number 12—December 2025
Research
Silent Propagation of Classical Scrapie Prions in Homozygous K222 Transgenic Mice
Abstract
Classical scrapie affects sheep and goats. To control prevalence in sheep, the European Union initiated breeding programs targeting resilient genotypes. Although certain goat polymorphisms, such as Q222K, are linked to resistance, specific breeding programs have not been implemented. Hemizygous transgenic mice carrying the goat K222 cellular prion protein (PrP) allele (K222-Tg516) exhibited resistance to several classical scrapie isolates. We inoculated homozygous K222-Tg516 and Q222-Tg501 mice with various scrapie isolates. Homozygous K222-Tg516 mice reached the end of their lifespan without exhibiting clinical signs; we observed brain proteinase K–resistant PrP accumulation in those mice that was lower than in Q222-Tg501 mice. Histologically, K222-Tg516 brains lacked prion-related lesions, except for the presence of few isolated scrapie PrP plaques in cases of isolates highly adapted to the K222-PrPC environment. Our findings caution against including that polymorphism in breeding programs, because it could lead to emergence of asymptomatic silent prion carriers of classical scrapie among goat populations.
snip…
Discussion Previous studies conducted in heterozygous Q/K222 and homozygous K222 goats (20–23), as well as in hemizygous K222-Tg516 mice (29), have highlighted the Q222K polymorphism as one of the most promising candidates for reducing prion disease transmission in goats. Although the K222 allele has been consistently reported in certain countries in Europe, such as Italy (15,16), France (10), and Greece (17,42), in other countries, such as the United Kingdom, the polymorphism has been reported as infrequent (43). However, once the supposed protective effect against prion diseases is confirmed, the frequency of the K222 allele could increase across different countries through selective breeding programs.
Transgenic mice expressing K222-PrPC in homozygosity emerge as the optimal tool for definitively testing the susceptibility or resistance that allele confers to prions. Our model enables the testing of multiple prion strains more rapidly and cost-effectively than the model using goats. In our study, classical scrapie isolates representing different classical scrapie strains circulating within Europe (40–42) were selected and used to challenge homozygous K222-Tg516 mice.
Once the expression level is increased, homozygous K222-Tg516 mice become susceptible to all tested classical scrapie isolates (Table 3). The K222-PrPC variant is capable of sustaining PrPSc replication even in the absence of the Q222-PrPC variant, which was identified as responsible for most accumulated brain PrPres in Q222K heterozygous goats (24). Furthermore, K222-Tg516 mice exhibit consistently lower brain PrPres accumulation than Q222-Tg501 mice (Figure 1). The explanation that K222-PrPres is more sensitive to proteinase K treatment and so reduced detection of brain PrPres accumulation has been ruled out (Figure 6). Therefore, we recommend careful analysis of the general features and behavior of classical scrapie K222-PrPres.
K222-Tg516 mice inoculated with classical scrapie did not develop typical prion pathology and showed no clinical signs of prion disease, which suggests that classical scrapie K222-PrPres might not be toxic or might not induce the signaling pathways leading to neuronal death. Those conclusions are not only caused by insufficient time for the onset of neuronal death pathways within the animal lifespan; second passages in K222-Tg516 yielded identical results to the first ones. However, we noted that the lower brain PrPres accumulation in K222-Tg516 animals could lead to a misinterpretation of those results. The reduced accumulation might reflect insufficient replication within the animal’s lifespan, possibly caused by consistently low replication rates, as suggested by our kinetic experiments, or by more efficient clearance of PrPres aggregates. Those factors could explain why transmission does not necessarily result in prion disease, highlighting a dissociation between infectivity and toxicity of classical scrapie K222-PrPres.
All circulating prion strains must be considered in the design of breeding selection programs. Programs aimed at controlling and reducing classical scrapie in sheep, implemented by EU member states, have identified sheep herds that are more susceptible to atypical/Nor98 scrapie (44). In our study, K222-Tg516 mice died without exhibiting overt clinical signs after inoculation with different classical scrapie isolates; we found that PrPres accumulated in their brains (Table 1). Of note, K222-derived PrPres retained infectivity when transmitted back to Q222-Tg501 mice, recovering the strain characteristics observed in the original inocula. Our findings suggest that, under the experimental conditions we established, the K222 allele does not confer full resistance to classical scrapie agents.
Of interest, the reversibility of strain features observed upon reinoculation of K222-derived PrPres into Q222-Tg501 mice is reminiscent of the phenomenon of nonadaptive prion amplification as described previously (45). In that model, PrPSc can replicate transiently in a nonpermissive host without inducing a permanent adaptation of the strain. Our data are consistent with that concept; the classical scrapie agents replicated in K222-Tg516 mice but reverted to their original biochemical and biologic properties upon passage back into a permissive Q222 context. That interpretation reinforces the view that the K222 allele may enable subclinical or low-efficiency replication of classical scrapie agents without supporting stable strain selection or adaptation.
It is important to note that the use of transgenic models with PrP overexpression may enhance prion replication efficiency, potentially uncovering low-level or subclinical conversion events that might not occur under physiologic PrP expression in goats. In addition, all animals were inoculated intracerebrally; that route does not mimic natural exposure and bypasses key peripheral barriers such as the gut and associated lymphoid tissues, which play a critical role in determining prion susceptibility and pathogenesis under field conditions. Therefore, although our results highlight the potential for silent propagation of classical scrapie strains in the context of the K222 variant, extrapolation to the natural host should be made with caution.
Interest has grown for in-depth characterization of the strains of Q/K222 heterozygous goats affected with scrapie, which are abundant in various regions of Greece. The interest lies in determining whether prions propagated under the K222 allele can act as potential silent carriers of the disease, as shown in previous studies. Furthermore, understanding whether the presence of the K222 allele induces a change in the biologic properties of the strains and their potential transmission to other animal species is crucial.
Overall, our results underscore the need for further in vivo studies using physiologically relevant models or natural hosts to fully evaluate the protective efficacy of the K222 allele. Until such evidence becomes available, the inclusion of the K222 polymorphism in breeding selection programs should be critically considered, especially in regions where classical scrapie strains with known zoonotic potential remain present. Furthermore, experiments conducted in classical BSE-inoculated Q/K222 heterozygous goats have shown at least low infectivity in goat tissues after long postinoculation periods (26), whereas heterozygous K222-Tg516 mice were already fully susceptible to goat BSE (29). In addition, at least 1 Q/K222 heterozygous goat tested positive for atypical/Nor98 scrapie (28), and homozygous K222-Tg516 mice were found to be completely susceptible to atypical/Nor98 scrapie (30). Taken together, those data suggest that the protective effect of the Q222K polymorphism may be limited, and its use in breeding programs should be carefully evaluated.
Dr. Fernández-Borges is a tenured researcher in the Laboratory of Molecular and Cellular Biology of Prions at Centro de Investigación en Sanidad Animal (CISA-INIA-CSIC). Her research interests include prion strain characterization and evolution and the pathogenesis of prion diseases and their effects on human and animal health.
Acknowledgments
https://wwwnc.cdc.gov/eid/article/31/12/25-0302_article
Scrapie typical and atypical USA
FY 2023, 16,646 from sheep and 8,726 from goats.
* There have been 491 NVSL confirmed positive animals (474 classical cases – 471 sheep and 3 goats) and
19 Nor98- like cases since the beginning of RSSS. Figure 3 depicts RSSS collection sites in FY 2023.
https://www.aphis.usda.gov/sites/default/files/scrapie-annual-report.pdf
In 2023, APHIS collected samples from more than 26,000 sheep and goats for scrapie testing. Out of the total number of animals tested in 2023, no animals tested positive for classical scrapie and
one sheep tested positive for non-classical scrapie (Nor98-like)...
https://www.usda.gov/sites/default/files/documents/22-APHIS-2025-ExNotes.pdf
In 2022, APHIS collected samples from more than 23,000 sheep and goats for scrapie testing. Out of the total number of animals tested in 2022, no animals tested positive for classical scrapie and
one sheep tested positive for non-classical scrapie (Nor98-like).
https://www.usda.gov/sites/default/files/documents/23-2024-APHIS.pdf
In FY 2021, APHIS collected samples from more than 30,000 sheep and goats for scrapie testing. Out of the total number of samples processed and reported in FY 2021,
one sheep tested positive for classical scrapie and one sheep tested positive for non-classical scrapie (Nor98-like).
https://www.usda.gov/sites/default/files/documents/23-2023-APHIS.pdf
In FY 2020, APHIS collected samples from 33,839 sheep and goats for scrapie testing. This number represents sample results reported by October 15, 2020 and is expected to slightly increase as the remaining results are processed and reported. No animals tested positive for classical scrapie.
Two sheep tested positive at slaughter for non-classical scrapie (Nor98-like).
https://www.usda.gov/sites/default/files/documents/22APHIS2022Notes.pdf
In FY 2019, APHIS collected samples from 34,730 sheep and goats for scrapie testing, detecting 7 classical scrapie positive animals. Of these animals, five sheep and one goat were from a source flock in Pennsylvania that was found in August 2018, depopulated in October 2018, and tested for scrapie in November 2018. A second goat, which was from an Indiana herd, was sampled at slaughter in June 2019. The source flock completed a cleanup plan and was placed on a 5-year monitoring plan. The source herd of the positive Indiana goat no longer contained any exposed animals and was also placed on a 5-year monitoring plan. A trace-back investigation narrowed the goat’s birth herd to two possible herds. Animals in both herds tested negative for scrapie and were placed on 5-year monitoring plans. There were no classical scrapie cases detected in slaughter sheep in FY 2019.
Also in FY 2019, two sheep tested positive at slaughter for non-classical scrapie (Nor98-like) and were traced back to Colorado flocks.
https://www.usda.gov/sites/default/files/documents/20aphis2021notes.pdf
In FY 2018, APHIS collected samples from 43,625 sheep and goats for scrapie testing, detecting three positive (0.0068%) cases. These figures are based on sample submissions and testing completed by September 30, 2018. FY 2018 values are expected to change when testing is completed for all animals sampled in FY 2018.
In October 2017, a non-classical scrapie case was detected in a sheep from Virginia sampled at slaughter. As a result, the non- classical scrapie affected flock was placed on a 5-year monitoring plan.
https://www.usda.gov/sites/default/files/documents/20aphis2020notes.pdf
In FY 2016, the program identified one flock infected with classical scrapie and one infected with Nor98-like scrapie through slaughter surveillance, and two flocks infected with classical scrapie through on-farm surveillance.
An additional 10 sheep were confirmed with classical scrapie through testing of sheep depopulated from these infected flocks as part of flock clean-up activities conducted in FY 2016.
The Nor98-like scrapie affected flock will be placed on a 5-year monitoring plan.
https://www.usda.gov/sites/default/files/documents/20aphisexnotes2018.pdf
please see
2026 USDA EXPLANATORY NOTES, APHIS, CWD, BSE, Scrapie, TSE, Prion
https://transmissiblespongiformencephalopathy.blogspot.com/2025/12/2026-usda-explanatory-notes-aphis-cwd.html
https://transmissiblespongiformencephalopathy.blogspot.com/2025/12/2026-usda-explanatory-notes-aphis-cwd.html
Classical BSE emergence from Nor98/atypical scrapie: Unraveling the shift vs. selection dichotomy in the prion field
Sara Canoyra, Alba Marín-Moreno, Juan Carlos Espinosa , and Juan María Torres
Authors Info & Affiliations Edited by Byron Caughey, National Institute of Allergy and Infectious Diseases (National Institutes of Health), Hamilton, MT; received January 17, 2025; accepted June 7, 2025 by Editorial Board Member Lila M. Gierasch
July 15, 2025
122 (29) e2501104122 https://doi.org/10.1073/pnas.2501104122
Significance
Classical bovine spongiform encephalopathy (c-BSE) is a fatal cattle prion disease transmissible to humans as variant Creutzfeldt–Jakob Disease (vCJD). Understanding how c-BSE emerges is crucial for preventing future outbreaks and protecting public health. Two main hypotheses explain prion adaptation during cross-species transmission: “conformational shift or deformed templating,” where the species barrier forces a change to a different pathological prion protein, and “conformational selection,” where the species barrier filters preexisting conformers. Our results demonstrate that the conformational shift mechanism explains the emergence of c-BSE when Nor98/atypical scrapie (AS) is transmitted to cattle. This is significant because AS, found in sheep and goats worldwide, can convert to c-BSE. Preventing AS from entering the food chain is crucial to reduce c-BSE/vCJD risks.
Abstract
Prion diseases can manifest with distinct phenotypes in a single species, a phenomenon known as prion strains. Upon cross-species transmission, alterations in the disease phenotype can occur, interpreted as the emergence of a new strain. Two main and non–mutually exclusive evolutionary hypotheses have been proposed to explain this phenomenon: the “conformational shift” or “deformed templating” and the “conformational selection.” The conformational shift hypothesis proposes that the introduction of a new host prion protein (PrPC) forces a change in the conformation of the pathological prion protein (PrPSc), causing the new prion strain emergence. On the contrary, the conformational selection model postulates that prion isolates are a conglomerate of PrPSc conformations with relative distribution frequencies, wherein the species barrier acts as a filter selecting the one fittest for the new species environment. Previous studies reported the emergence of the classical bovine spongiform encephalopathy agent (c-BSE) upon transmission of Nor98/atypical scrapie (AS) onto a bovine PrP. This study investigates the evolutionary dichotomy of this c-BSE emergence by using prion strain thermostability combined with protein misfolding cyclic amplification to distinguish between both strains. Our results suggest that the conformational shift could be the principal mechanism responsible for the c-BSE emergence. Furthermore, the selection model was dismissed as the key mechanism based on the analysis of an artificial c-BSE and AS mixture. The ability of the AS conformers to shift conformation to a c-BSE one supports the hypothesis that the epidemic c-BSE prion may have originated from the transmission of AS in cattle.
https://www.pnas.org/doi/abs/10.1073/pnas.2501104122?download=true
Published: 04 October 2023
Detection of classical BSE prions in asymptomatic cows after inoculation with atypical/Nor98 scrapie
Marina Betancor, Belén Marín, Alicia Otero, Carlos Hedman, Antonio Romero, Tomás Barrio, Eloisa Sevilla, Jean-Yves Douet, Alvina Huor, Juan José Badiola, Olivier Andréoletti & Rosa Bolea Veterinary Research volume 54, Article number: 89 (2023) Cite this article
Abstract
The emergence of bovine spongiform encephalopathy (BSE) prions from atypical scrapie has been recently observed upon experimental transmission to rodent and swine models. This study aimed to assess whether the inoculation of atypical scrapie could induce BSE-like disease in cattle. Four calves were intracerebrally challenged with atypical scrapie. Animals were euthanized without clinical signs of prion disease and tested negative for PrPSc accumulation by immunohistochemistry and western blotting. However, an emergence of BSE-like prion seeding activity was detected during in vitro propagation of brain samples from the inoculated animals. These findings suggest that atypical scrapie may represent a potential source of BSE infection in cattle.
Snip…
Discussion
Previous studies have demonstrated that C-BSE prions can be present as a minor variant in ovine atypical scrapie isolates and that C-BSE can emerge during the passage of these isolates to pigs and bovine PrP mice [7, 8]. These results pointed to atypical scrapie as a possible origin of C-BSE. Therefore, this study was meant to assess the link between atypical scrapie and C-BSE in the natural host of C-BSE, cattle. Although the intracerebral challenge has some limitations and does not reflect the natural transmission process of prions, bioassays using experimental prion inoculation have allowed to identify and describe the transmission mechanisms of these pathogens. Therefore, we decided to challenge cattle with an atypical scrapie isolate.
It is important to note that none of the animals in this study showed any clinical signs of TSE after inoculation with atypical scrapie, according to the results previously obtained in pigs [8]. In addition, the absence of spongiform changes in brain sections, as well as the absence of PrPSc accumulation by conventional techniques in brain areas from the atypical scrapie-inoculated cows, further highlights the need for highly sensitive techniques such as PMCA to detect low levels of prions. After the in vitro propagation of brain samples from the cows included in this study, seeding activity was detected in reactions seeded with brain material from three out of the four cows, in the areas of frontal cortex, thalamus, and/or cerebellum. Interestingly, none of the samples from the obex, which is one of the most affected areas in prion diseases [14], showed seeding activity. Importantly, the observed glycosylation pattern of the positive PMCA reactions was indistinguishable from that of C-BSE prions and PMCA products from reactions seeded with C-BSE prions. To check whether C-BSE-like prions were present in the original atypical scrapie isolate or if they emerged in the brain of the cows after the inoculation, we performed PMCA of the original inoculum in TgBov substrate, following the same conditions described above. The in vitro amplification of the atypical scrapie inoculum resulted in the propagation of BSE-like seeding activity, biochemically indistinguishable from C-BSE or positive PMCA reactions seeded with brain samples from the inoculated cows, suggesting that, as described before, certain atypical scrapie isolates contain low levels of C-BSE prions [9].
Moreover, in order to rule out a spontaneous in vitro misfolding of bovine PrP during PMCA, we included, as a control for the technique, brain samples from non-inoculated age-matching cows that were also subjected to serial in vitro propagation in TgBov substrate. No positivity was observed in PMCA reactions seeded with samples from these animals, suggesting a true C-BSE-like prion seeding activity and not a spontaneous in vitro misfolding of PrP.
All these results suggest the amplification of C-BSE-like prions during the transmission of ovine atypical scrapie to cows. It is true that, in order to confirm the presence of infectious BSE prions in the challenged cows, strain typing experiments of the PMCA products should be carried out in established mouse lines. Therefore, studies involving a bioassay in bovine and ovine PrP-expressing mice have been started.
Interestingly, the time after inoculation and the BSE-like prion seeding activity were not correlated. As previously stated, the emergence of C-BSE from atypical scrapie has been associated with the presence of low levels of C-BSE prions in the atypical scrapie isolates and our results after the in vitro amplification of the PS152 inoculum support this theory. Therefore, the number of C-BSE conformers contained in the used atypical scrapie isolates may be reduced and not homogeneously distributed, making cows receiving different amounts of C-BSE-like prions. It is true that the emergence of C-BSE-like PMCA seeding activity from the brains of cows could be related to the persistence of prions from the original atypical scrapie inoculum. Previous studies, in which prion seeding activity was detected in the brain of intracerebrally inoculated PrP0/0 mice have highlighted the capacity of prions to persist in non-replicative environments [15]. Nevertheless, cows were intracerebrally challenged in the frontal cortex, and seeding activity was detected in caudal regions of their brains but not in more rostral areas such as the frontal cortex. If these positive PMCA reactions were not a bona fide propagation of C-BSE-like prions but associated to inoculum persistence, it would be expected to detect such amplification in the most rostral areas of the brain. Although all these results support a bona fide propagation of C-BSE-like prions, the possibility of PMCA detecting remaining prions of the inoculum, would be definitely ruled out after in vivo bioassays in mouse lines, which are currently being carried out.
The lack of clinical signs of prion disease in cows after inoculation with atypical scrapie contrasts with results from a previous study in which bovine PrP mice (TgBov) were challenged with atypical scrapie isolates and displayed signs of clinical prion disease, developing neuropathological characteristics of C-BSE [7]. In addition, in the mentioned study, after the first passage, signs of clinical prion disease were only observed in a low proportion of the inoculated mice, and several of the inoculated isolates did not lead to PrPSc accumulation. Three serial passages of atypical scrapie were needed to observe complete attack rates in TgBov mice. Moreover, mice from the first passage that developed clinical signs showed long incubation periods considering the lifespan of a mouse. The cows in this study were also euthanized after a long post-inoculation period (between ~7 and ~11 years). However, the number of C-BSE-like prions present in the original atypical scrapie inoculum was probably too low to produce disease in the cows upon first passage. We also need to consider that TgBov mice overexpress ~8 times bovine PrPC, making them more susceptible to develop disease after the inoculation of C-BSE prions.
Further in vivo experiments challenging different mouse lines have been started in order to confirm the infectivity of the PMCA products obtained in this study. However, in conclusion, our findings show that the propagation of atypical scrapie in cattle leads to the emergence of BSE-like seeding activity. This is a concerning issue with far-reaching implications for public health and food safety. The possibility of interspecies transmission of prion diseases and the emergence of new prion strains highlight the critical need for continued surveillance and monitoring of these diseases in both animal and human populations. Early detection of prion diseases is crucial, and highly sensitive detection techniques such as PMCA can play an important role in this regard.
https://veterinaryresearch.biomedcentral.com/articles/10.1186/s13567-023-01225-2
Classical BSE prions emerge from asymptomatic pigs challenged with atypical/Nor98 scrapie
Belén Marín, Alicia Otero, Séverine Lugan, Juan Carlos Espinosa, Alba Marín-Moreno, Enric Vidal, Carlos Hedman, Antonio Romero, Martí Pumarola, Juan J. Badiola, Juan María Torres, Olivier Andréoletti & Rosa Bolea
Scientific Reports volume 11, Article number: 17428 (2021) Cite this article
Abstract
Pigs are susceptible to infection with the classical bovine spongiform encephalopathy (C-BSE) agent following experimental inoculation, and PrPSc accumulation was detected in porcine tissues after the inoculation of certain scrapie and chronic wasting disease isolates. However, a robust transmission barrier has been described in this species and, although they were exposed to C-BSE agent in many European countries, no cases of natural transmissible spongiform encephalopathies (TSE) infections have been reported in pigs. Transmission of atypical scrapie to bovinized mice resulted in the emergence of C-BSE prions. Here, we conducted a study to determine if pigs are susceptible to atypical scrapie. To this end, 12, 8–9-month-old minipigs were intracerebrally inoculated with two atypical scrapie sources. Animals were euthanized between 22- and 72-months post inoculation without clinical signs of TSE. All pigs tested negative for PrPSc accumulation by enzyme immunoassay, immunohistochemistry, western blotting and bioassay in porcine PrP mice. Surprisingly, in vitro protein misfolding cyclic amplification demonstrated the presence of C-BSE prions in different brain areas from seven pigs inoculated with both atypical scrapie isolates. Our results suggest that pigs exposed to atypical scrapie prions could become a reservoir for C-BSE and corroborate that C-BSE prions emerge during interspecies passage of atypical scrapie.
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Discussion The outbreak of C-BSE was followed by the appearance of TSE in species that had never been diagnosed with prion diseases and the emergence in humans of vCJD16,17,18. However, no natural prion disease has been described in pigs, even though they were exposed to C-BSE contaminated feed12. Posterior experimental challenges in pigs and mice expressing porcine PrP have demonstrated that, although they are not completely resistant, pigs present a robust transmission barrier for C-BSE prions4,14,19.
However, the possible transmission of a TSE to swine is a public health concern due to the wide use of pork as a source of human food, and the increasing use of pigs as tissue donors, being reported a case of vCJD in a human patient receiving a swine dura mater graft20. Although pigs are apparently non-susceptible to C-BSE after oral challenge4,5,21, infectivity has been detected in tissues from pigs orally inoculated with classical scrapie or CWD10,11. In addition, these positive orally inoculated pigs are often subclinical, what could represent a public health concern, considering that these animals could reach the slaughterhouse without showing signs suggestive of prion disease.
In the present study, we evaluated the transmissibility of atypical scrapie to pigs. Pigs were euthanized between 22- and 72-months post inoculation (mpi), and their tissues tested for PrPSc accumulation and infectivity. We did not find evidence of transmission of atypical scrapie to any of the animals by EIA (Table 2), western blotting, or mouse bioassay (Table 3). PrPSc accumulation can be detected in BSE-challenged pigs at 34 mpi4, and at 22 mpi when inoculated with SBSE7. Although scrapie or CWD-inoculated pigs do not show clinical signs, PrPSc presence can be found in scrapie-challenged animals at 51 mpi11 and as early as 6 mpi in the case of CWD10.
Our main goal was to test the ability of atypical scrapie/Nor98 strain to propagate in swine, given that mice expressing porcine PrP (PoPrP-Tg001/tgPo mice) showed to be susceptible to atypical scrapie inoculation. One atypical scrapie isolate adapted to this transgenic line, reaching a 100% attack rate and rapid incubation periods in serial passages13, a similar adaptation to that observed with the C-BSE agent19. However, when this atypical scrapie isolate was tested for propagation in tgPo mice again, together with other atypical scrapie isolates, no positive results were obtained, in vitro nor in vivo14. These results, together with the negative transmissions showed in the present study, reinforce the conclusion that porcine species is highly resistant to atypical scrapie. However, we only performed one passage in tgPo mice, and further passages in this line and/or PMCA analysis of tgPo brains to detect any possible prion replication would be of interest.
However, it was demonstrated that C-BSE prions can be present as a minor variant in ovine atypical scrapie isolates and that C-BSE can emerge during the passage of these isolates to bovine PrP mice15. Considering that the aforementioned atypical scrapie isolate also acquired BSE-like properties when transmitted to tgPo mice13, and that C-BSE is the only prion that efficiently propagates in swine PrP4,7,14, we decided to investigate whether C-BSE prions could emerge from atypical scrapie during the ovine-porcine interspecies transmission.
Interestingly, PMCA reactions seeded with brain material from 7 pigs propagated in tgBov substrate showing PrPres with identical biochemical characteristics to those of C-BSE (Fig. 1). Positive C-BSE amplification was detected in the brain of pigs inoculated with either the PS152 or TOA3 atypical scrapie isolates, at minimum incubation periods of 28- and 35-months post inoculation, respectively. From each animal, positive reactions were not obtained from all brain areas tested (Supplementary table 1). Although PrPres amplified from the pigs showed C-BSE biochemical characteristics, further bioassays in tgBov mice are required to know whether these prions replicate the neuropathological features of C-BSE.
Altogether, our results and data obtained from transmission studies of prions to pigs, tgPo mice and in vitro studies using porcine substrate have shown that pig PrP has a very limited ability to sustain prion replication. No significant polymorphisms have been described for pig PRNP22, and it has been suggested that the conformational flexibility of pig PrP sequence is very low, limiting the number of PrPSc conformations able to produce misfolding14. No differences have been found between pig and minipig PrP sequences either23, suggesting that the conclusions obtained here could be extrapolated to domestic, non-experimental pigs. However, using tgBov substrate, we have demonstrated in vitro the presence of C-BSE seeding activity in some pig brain areas, suggesting that C-BSE prions emerged during the transmission of ovine atypical scrapie prions to pigs. Interestingly, C-BSE prions did not emerge from brain material of all the pigs, and, of those from which it did emerge, it was not detected in all brarsain areas tested. No correlation between time after inoculation and BSE emergence was found either. When the emergence of C-BSE from atypical scrapie in PMCA was described, it was associated to low levels of C-BSE prions that were present in the original atypical scrapie isolates15. It is possible that this result is related to the great resistance that pigs present to prion diseases, making the penetrance of the BSE prions that could be present in the original inoculum incomplete. In addition, considering that the amount of C-BSE conformers in the atypical scrapie inocula is probably very reduced and perhaps not homogeneously distributed throughout the isolate, it is also possible that not all the pigs received a sufficient amount of C-BSE conformers capable of being detected by PMCA. Finally, we should consider that PMCA amplification of prions is sometimes a stochastic phenomenon, which could explain why no C-BSE propagation was obtained from some of the pigs. It could be also discussed that C-BSE emergence from the pig brains could be related to persistence of the original atypical scrapie inoculum. However, C-BSE amplification was not obtained from all of the pigs and, in some of them (i.e. P-1217 and P-1231) C-BSE propagation was detected in caudal regions of the brain (cerebellum or occipital cortex) but not in more rostral areas (such as parietal cortex). If C-BSE amplification from pig brain samples were associated to inoculum persistence and not bona fide propagation of C-BSE prions it would be expected that such amplification would be detected mainly in the most rostral areas of the brain. Finally, even though the titer generated was not enough to produce disease in the pigs, these results evidence again the issue that pigs could act as subclinical reservoirs for prion diseases as observed with scrapie and CWD, and that the presence of prions can be detected in pigs short after exposure to prions7,10,11.
In conclusion, our findings suggest that, although pigs present a strong transmission barrier against the propagation of atypical scrapie, they can propagate low levels of C-BSE prions. The prevalence of atypical scrapie and the presence of infectivity in tissues from atypical scrapie infected sheep are underestimated24,25. Given that pigs have demonstrated being susceptible to other prion diseases, and to propagate prions without showing signs of disease, the measures implemented to ban the inclusion of ruminant proteins in livestock feed must not be interrupted.
https://www.nature.com/articles/s41598-021-96818-2
The prevalence of atypical scrapie and the presence of infectivity in tissues from atypical scrapie infected sheep are underestimated24,25. Given that pigs have demonstrated being susceptible to other prion diseases, and to propagate prions without showing signs of disease, the measures implemented to ban the inclusion of ruminant proteins in livestock feed must not be interrupted.
https://nor-98.blogspot.com/2021/10/classical-bse-prions-emerge-from.html
EFSA atypical Scrapie
***> AS is considered more likely (subjective probability range 50–66%) that AS is a non-contagious, rather than a contagious, disease.
SNIP...SEE;
THURSDAY, JULY 8, 2021
EFSA Scientific report on the analysis of the 2‐year compulsory intensified monitoring of atypical scrapie
***> AS is considered more likely (subjective probability range 50–66%) that AS is a non-contagious, rather than a contagious, disease.
https://efsa.onlinelibrary.wiley.com/doi/10.2903/j.efsa.2021.6686
https://efsa.onlinelibrary.wiley.com/doi/full/10.2903/j.efsa.2021.6686
https://efsa.onlinelibrary.wiley.com/doi/epdf/10.2903/j.efsa.2021.6686
https://efsaopinionbseanimalprotein.blogspot.com/2021/07/efsa-scientific-report-on-analysis-of.html
***> Incomplete inactivation of atypical scrapie following recommended autoclave decontamination procedures <***
John Spiropoulos Richard Lockey Katy E. Beck Chris Vickery Thomas M. Holder Leigh Thorne Mark Arnold Olivier Andreoletti Marion M Simmons Linda A. Terry First published: 21 May 2019 https://doi.org/10.1111/tbed.13247 This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/tbed.13247
Summary Prions are highly resistant to the decontamination procedures normally used to inactivate conventional pathogens. This is a challenging problem not only in the medical and veterinary fields for minimising the risk of transmission from potentially infective sources, but also for ensuring the safe disposal or subsequent use of animal by‐products. Specific pressure autoclaving protocols were developed for this purpose, but different strains of prions have been reported to have differing resistance patterns to established prion decontamination procedures, and as additional TSE strains are identified it is necessary to determine the effectiveness of such procedures. In this study we assessed the efficacy of sterilisation using the EU recommended autoclave procedure for prions (133o C, 3 Bar for 20 min) on the atypical or Nor98 (AS/Nor98) scrapie strain of sheep and goats. Using a highly sensitive murine mouse model (tg338) that overexpresses ovine PrPC, we determined that this method of decontamination reduced the infectivity titre by 1010. Infectivity was nonetheless still detected after applying the recommended autoclaving protocol. This shows that AS/Nor98 can survive the designated legislative decontamination conditions, albeit with a significant decrease in titre. The infectivity of a classical scrapie isolate subjected to the same decontamination conditions was reduced by 106 suggesting that the AS/Nor98 isolate is less sensitive to decontamination than the classical scrapie source. This article is protected by copyright. All rights reserved.
https://onlinelibrary.wiley.com/doi/abs/10.1111/tbed.13247
Saturday, May 2, 2009
APHIS AND WHO PLAN TO EXEMPT THE ATYPICAL SCRAPIE NOR-98 FROM REGULATIONS AT MEETING THIS MONTH
http://nor-98.blogspot.com/2009/05/aphis-and-who-plan-to-exempt-atypical.html
Monday, November 30, 2009
USDA AND OIE COLLABORATE TO EXCLUDE ATYPICAL SCRAPIE NOR-98 ANIMAL HEALTH CODE
http://nor-98.blogspot.com/2009/11/usda-and-oie-collaborate-to-exclude.html
Thursday, December 20, 2012
OIE GROUP RECOMMENDS THAT SCRAPE PRION DISEASE BE DELISTED AND SAME OLD BSe WITH BOVINE MAD COW DISEASE
http://transmissiblespongiformencephalopathy.blogspot.com/2012/12/oie-group-recommends-that-scrape-prion.html
Experimental transmission of ovine atypical scrapie to cattle
Timm Konold, John Spiropoulos, Janet Hills, Hasina Abdul, Saira Cawthraw, Laura Phelan, Amy McKenna, Lauren Read, Sara Canoyra, Alba Marín-Moreno & Juan María Torres
Veterinary Research volume 54, Article number: 98 (2023)
Abstract
Classical bovine spongiform encephalopathy (BSE) in cattle was caused by the recycling and feeding of meat and bone meal contaminated with a transmissible spongiform encephalopathy (TSE) agent but its origin remains unknown. This study aimed to determine whether atypical scrapie could cause disease in cattle and to compare it with other known TSEs in cattle. Two groups of calves (five and two) were intracerebrally inoculated with atypical scrapie brain homogenate from two sheep with atypical scrapie. Controls were five calves intracerebrally inoculated with saline solution and one non-inoculated animal. Cattle were clinically monitored until clinical end-stage or at least 96 months post-inoculation (mpi). After euthanasia, tissues were collected for TSE diagnosis and potential transgenic mouse bioassay. One animal was culled with BSE-like clinical signs at 48 mpi. The other cattle either developed intercurrent diseases leading to cull or remained clinical unremarkable at study endpoint, including control cattle. None of the animals tested positive for TSEs by Western immunoblot and immunohistochemistry. Bioassay of brain samples from the clinical suspect in Ov-Tg338 and Bov-Tg110 mice was also negative. By contrast, protein misfolding cyclic amplification detected prions in the examined brains from atypical scrapie-challenged cattle, which had a classical BSE-like phenotype. This study demonstrates for the first time that a TSE agent with BSE-like properties can be amplified in cattle inoculated with atypical scrapie brain homogenate.
snip...
This is the first study in cattle inoculated with naturally occurring scrapie isolates that found the presence of prions resembling classical BSE in bovine brain although this was limited to detection by the ultrasensitive PMCA. The results from thermostability assay confirmed that the isolates were as thermoresistant as the BSE agent as proven in other studies [36, 48]. Previous PMCA studies with various British atypical scrapie isolates did not find any evidence of amplification [49, 50]. This may be explained by the use of ovine brain as substrate rather than brain from Bov-Tg110 mice, which may facilitate conversion to classical BSE prions.
Two hypotheses for prion strain propagation in cross-species transmission experiments have been proposed: conformational selection favours a particular strain conformation out of a mixture of conformations in a scrapie isolate whilst mutation results in the conformational shift of one conformation into another [51]. Following on from the study in mice [17], it has been subsequently suggested that classical BSE properties that arise in atypical scrapie isolates transmitted to cattle may be due to conformational mutation in a new host [52]. It does not confirm that the atypical scrapie agent is the origin of the classical BSE epidemic and further transmission studies would be required to see whether classical BSE can be generated.
Would PMCA applied to brains from cattle exposed to TSE agents other than classical BSE and atypical scrapie also produce a classical BSE-like molecular phenotype? The PMCA product obtained in the thermostability test using a thermosensitive classical scrapie control showed a profile unlike classical BSE. Atypical BSE has been linked to the origin of classical BSE because of its conversion into classical BSE following serial passages in wild-type mice (L-type BSE [11]) and bovine transgenic mice (H-type BSE [53]). Although we have not tested PMCA products of atypical BSE isolates as part of this study, there is no evidence that PMCA products from atypical BSE convert into classical BSE, at least for H-type BSE using bovine brain as substrate [54]. In fact, we were unable to propagate H-type BSE using the same methodology (S Canoyra, A Marín-Moreno, JM Torres, unpublished observation).
The study results support the decision to maintain the current ban on animal meal in feedstuffs for ruminants, particularly as atypical scrapie occurs world-wide, and eradication is unlikely for a sporadic disease.
In summary, experimental inoculation of cattle with the atypical scrapie agent may produce clinical disease indistinguishable from classical BSE, which cannot be diagnosed by conventional diagnostic tests, but prions can be amplified by ultrasensitive tests in both clinically affected and clinically unremarkable cattle, which reveal classical BSE-like characteristics. Further studies are required to assess whether a BSE-like disease can be confirmed by conventional tests, which may initially include a second passage in cattle.
https://veterinaryresearch.biomedcentral.com/articles/10.1186/s13567-023-01224-3
Volume 17, Number 5—May 2011
Research
Experimental Oral Transmission of Atypical Scrapie to Sheep
Marion M. SimmonsComments to Author , S. Jo Moore1, Timm Konold, Lisa Thurston, Linda A. Terry, Leigh Thorne, Richard Lockey, Chris Vickery, Stephen A.C. Hawkins, Melanie J. Chaplin, and John Spiropoulos
Author affiliations: Author affiliation: Veterinary Laboratories Agency–Weybridge, Addlestone, UK Cite This Article
Abstract
To investigate the possibility of oral transmission of atypical scrapie in sheep and determine the distribution of infectivity in the animals’ peripheral tissues, we challenged neonatal lambs orally with atypical scrapie; they were then killed at 12 or 24 months. Screening test results were negative for disease-specific prion protein in all but 2 recipients; they had positive results for examination of brain, but negative for peripheral tissues. Infectivity of brain, distal ileum, and spleen from all animals was assessed in mouse bioassays; positive results were obtained from tissues that had negative results on screening. These findings demonstrate that atypical scrapie can be transmitted orally and indicate that it has the potential for natural transmission and iatrogenic spread through animal feed. Detection of infectivity in tissues negative by current surveillance methods indicates that diagnostic sensitivity is suboptimal for atypical scrapie, and potentially infectious material may be able to pass into the human food chain.
Snip…
Discussion This study is still ongoing and will not be completed until 2012. However, the current interim report documents the successful oral transmission of atypical scrapie, confirms that the disease phenotype is retained following transmission by this route in AHQ/AHQ sheep, and indicates that infectivity can be demonstrated in the gut in the absence of detectable PrPSc at least as early as 12 months after exposure.
One sheep (animal 12) culled at 24 months post inoculation displayed abnormalities in behavior and movement suggestive of atypical scrapie. Signs like ataxia with head tremor and circling have been described in experimental (19) and natural (3,30) disease, which was attributed to lesions in the cerebellum and forebrain, respectively, corresponding with PrPSc accumulation in these areas (20,24).
By contrast, animal 11, which had confirmed atypical scrapie based on postmortem tests, was considered clinically normal. The less severe and limited PrPSc accumulation in the brain of this sheep than in animal 12 may explain the absence of clinical abnormalities, which is supported by our findings in goats with scrapie in which more extensive PrPSc accumulation in the brain was usually associated with a more severe clinical disease (25).
Although all TSEs are transmissible after intracerebral challenge to a susceptible host, only some are infectious under natural conditions. Therefore, it was important from a pathogenesis and disease control perspective to establish whether or not oral transmission can be successful. However, the challenge model in this study exposed animals as neonates, when the esophageal groove is operational and the lambs are physiologically monogastric. Exposure of 3-month-old ruminating animals to similar amounts of positive brain by the oral route have so far not resulted in any clinical disease, with all animals still alive >1,500 days post challenge (M.M. Simmons, unpub. data), but most natural cases have been recorded in animals older than this, so these animals may still progress to disease in the next few years. Since this challenge study in older animals has no time-kill component, and no losses caused by unrelated disease have occurred, whether any of these sheep are in a preclinical phase of disease is unknown. Unfortunately, the absence of detectable PrPSc in lymphoreticular tissues of sheep with atypical scrapie precludes the use of biopsies to ascertain early infection in these animals.
Transmission may be more efficient in newborn animals; the incubation periods of sheep orally infected with classical scrapie were significantly shorter in sheep challenged at 14 days of age than those challenged at 6 months of age (31). If, however, oral transmission is only effective in such young animals, then field exposure would most likely have to be through milk, which is known to be a highly effective route of transmission for classical scrapie (32). No data are currently available on the potential infectivity of milk from animals with atypical scrapie.
Successful oral transmission also raises questions regarding the pathogenesis of this form of disease. There must be passage of the infectious agent from the alimentary canal to the brain through one of several possible routes, most likely those that have been suggested and discussed in detail for other TSEs, for example, retrograde neuronal transportation either directly (33–35) or through lymphoid structures or hematogenously (36). Infectivity in the absence of readily demonstrable PrPSc has been reported (37–39), and although the mouse bioassay may detect evidence of disease in other tissues, these data may not be available for at least another 2 years. More protease-sensitive forms of PrPSc may be broken down more efficiently within cells and thus do not accumulate in peripheral tissues (19), enabling atypical PrPSc to transit the digestive tract and disseminate through other systems in small amounts before accumulating detectably in the central nervous system.
Although we do not have epidemiologic evidence that supports the efficient spread of disease in the field, these data imply that disease is potentially transmissible under field situations and that spread through animal feed may be possible if the current feed restrictions were to be relaxed. Additionally, almost no data are available on the potential for atypical scrapie to transmit to other food animal species, certainly by the oral route. However, work with transgenic mice has demonstrated the potential susceptibility of pigs, with the disturbing finding that the biochemical properties of the resulting PrPSc have changed on transmission (40). The implications of this observation for subsequent transmission and host target range are currently unknown.
How reassuring is this absence of detectable PrPSc from a public health perspective? The bioassays performed in this study are not titrations, so the infectious load of the positive gut tissues cannot be quantified, although infectivity has been shown unequivocally. No experimental data are currently available on the zoonotic potential of atypical scrapie, either through experimental challenge of humanized mice or any meaningful epidemiologic correlation with human forms of TSE. However, the detection of infectivity in the distal ileum of animals as young as 12 months, in which all the tissues tested were negative for PrPSc by the currently available screening and confirmatory diagnostic tests, indicates that the diagnostic sensitivity of current surveillance methods is suboptimal for detecting atypical scrapie and that potentially infectious material may be able to pass into the human food chain undetected.
https://wwwnc.cdc.gov/eid/article/17/5/10-1654_article
See updated studies on AS
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
AS
https://intcwdsympo.wordpress.com/wp-content/uploads/2023/06/final-agenda-with-abstracts.pdf
Abstract for Prion 2023
Title: Transmission of atypical BSE: a possible origin of Classical BSE in cattle
Authors: Sandor Dudas1, Samuel James Sharpe1, Kristina Santiago-Mateo1, Stefanie Czub1, Waqas Tahir1,2, *
Affiliation: 1National and WOAH reference Laboratory for Bovine Spongiform Encephalopathy, Canadian Food inspection Agency, Lethbridge Laboratory, Lethbridge, Canada. 2Department of Biological Sciences, University of Lethbridge, Lethbridge, Alberta, Canada.
*Corresponding and Presenting Author: waqas.tahir@inspection.gc.ca
Background: Bovine spongiform encephalopathy (BSE) is a fatal neurodegenerative disease of cattle and is categorized into classical and atypical forms. Classical BSE (CBSE) is linked to the consumption of BSE contaminated feed whereas atypical BSE is considered to be spontaneous in origin. The potential for oral transmission of atypical BSE is yet to be clearly defined.
Aims: To assess the oral transmissibility of atypical BSE (H and L type) in cattle. Should transmission be successful, determine the biochemical characteristics and distribution of PrPSc in the challenge cattle.
Material and Methods: For oral transmission, calves were fed with 100 g of either H (n=3) or L BSE (n=3) positive brain material. Two years post challenge, 1 calf from each of the H and L BSE challenge groups exhibited behavioural signs and were euthanized. Various brain regions of both animals were tested by traditional and novel prion detection methods with inconclusive results. To detect infectivity, brain homogenates from these oral challenge animals (P1) were injected intra-cranially (IC) into steer calves. Upon clinical signs of BSE, 3/4 of IC challenged steer calves were euthanized and tested for PrPSc with ELISA, immunohistochemistry and immunoblot.
Results: After 6 years of incubation, 3/4 animals (2/2 steers IC challenged with brain from P1 L-BSE oral challenge and 1/2 steer IC challenged with brain from P1 H-BSE oral challenge) developed clinical disease. Analysis of these animals revealed high levels of PrPSc in their brains, having biochemical properties similar to that of PrPSc in C-BSE.
Conclusion: These results demonstrate the oral transmission potential of atypical BSE in cattle. Surprisingly, regardless of which atypical type of BSE was used for P1 oral challenge, PrPSc in the P2 animals acquired biochemical characteristics similar to that of PrPSc in C-BSE, suggesting atypical BSE as a possible origin of C-BSE in UK.
Presentation Type: Oral Presentation
Funded by: CFIA, Health Canada, Alberta Livestock and Meat Agency, Alberta Prion
Research Institute
Grant Number: ALMA/APRI: 201400006, HC 414250
Abstract for Prion 2023
Acknowledgement: TSE unit NCAD, Lethbridge (Jianmin Yang, Sarah Bogart, Rachana Muley, Yuanmu Fang, Keri Colwell, Renee Anderson, John Gray, Rakhi Katoch) (CFIA, Canada), Dr. Catherine Graham (NSDA, Canada), Dr. Michel Levy (UCVM, Canada), Dr. Martin Groschup (FLI, Germany), Dr. Christine Fast (FLI, Germany), Dr. Bob Hills (Health Canada, Canada)
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
Final rule on the Importation of Sheep, Goats, and Certain Other Ruminants (APHIS-2009-0095) Scrapie, BSE, CWD, TSE Prion Singeltary Submission
https://scrapie-usa.blogspot.com/2021/12/final-rule-on-importation-of-sheep.html
MAD SHEEP OF MAD RIVER VALLEY
DECLARATION OF EXTRAORDINARY EMERGENCY BECAUSE OF AN ATYPICAL T.S.E. (PRION DISEASE) OF FOREIGN ORIGIN IN THE UNITED STATES [No. 00-072-1] August 15, 2000 OIG case # NY-3399-56 REDACTED, VT
History my 10 year plus FOIA requests and investigation into the truth of infamous Mad Sheep of Mad River Valley!
''Enclosed is OIG's notification that they have scheduled an investigation of the following individual. REDACTED is alleged to have provided possibly inaccurate test results involving diseased sheep. However, because the results were determined to be inconclusive, no actual violation was actually committed.''
https://foiamadsheepmadrivervalley.blogspot.com/
''However, because the results were determined to be inconclusive, no actual violation was actually committed.'' ...confused
Friday, February 20, 2015
***APHIS Freedom of Information Act (FOIA) Appeal Mouse Bio-Assays 2007-00030-A Sheep Imported From Belgium and the Presence of TSE Prion Disease Kevin Shea to Singeltary 2015
http://transmissiblespongiformencephalopathy.blogspot.com/2015/02/aphis-freedom-of-information-act-foia.html
http://www.amazon.com/Mad-Sheep-Story-behind-Family/dp/1933392762
i don't make this stuff up...
IN SHORT ;
August 15, 2000
OIG case # NY-3399-56 REDACTED, VT
''Enclosed is OIG's notification that they have scheduled an investigation of the following individual. REDACTED is alleged to have provided possibly inaccurate test results involving diseased sheep. However, because the results were determined to be inconclusive, no actual violation was actually committed.''
snip...
[don't all criminals wish this is the way the system worked. ...tss]
JULY, 28, 2000
Case Opening Memorandum
snip...
An investigation regarding the subject identified below will be conduced and a report submitted at the conclusion of the investigation. If you have or should later receive additional information concerning this matter, please forward it to this office.
If you believe that administrative action should be taken before all criminal and other legal matters are completed, please coordinate that action with this office in order not to jeopardize the ongoing investigation.
The fact that this subject is under investigation should not be discussed with anyone who does not have a need to know and all inquiries on the investigation should be referred to the office of Inspector General.
snip...end
FOR OFFICIAL USE ONLY FEBRUARY 7, 2002
SUBJECT OIG CASE NY-3399-56 REDACTED VT HEALTH/SANITATION VIOLATION
TO: William Buisch, Regional Director Eastern Region, VS Raleigh, NC
Enclosed is the official investigation report on REDACTED. If you will recall, REDACTED is alleged to have provided possible inaccurate test results involving diseased sheep.
OIG is closing their file upon issuance of the Report of Investigation (copy enclosed). We are, therefore, also closing our case file.
REDACTED
Resource Management Systems and Evaluation Staff
Enclosure
cc:
REDACTED IES, Riverdale, MD (w/cy of incoming)
APHIS:RMSES: REDACTED 2/7/02 "NY-3399-56-REDACTED Closure''
END...TSS
NOW, the question is, who screwed those test up, and was it done on purpose, just to cover someone's ass for letting those sheep in here in the first place ???
WHICH tests were compromised, one of them, all of them, and, can we trust the outcome of any of these test under the circumstances here ???
i.e.
"It is significant that four of the sheep which first tested positive on REDACTED Western blot tests, thereby providing the type of confirmation the plaintiffs argue is lacking on the current record."
UNDER what circumstances were these test compromised ???
MY basic, simple question, was not answered in layman term, i.e. exactly what strain of TSE did those sheep have ???
IS this the best we can do ??? "REDACTED is alleged to have provided possibly inaccurate test results involving diseased sheep. However, because the results were determined to be inconclusive, no actual violation was actually committed.''<<< Saturday, February 27, 2010
*** FINAL REPORT OF THE TESTING OF THE BELGIAN (VERMONT) SHEEP February 27, 2010 IN SHORT ; August 15, 2000 OIG case # NY-3399-56 REDACTED, VT ''Enclosed is OIG's notification that they have scheduled an investigation of the following individual. REDACTED is alleged to have provided possibly inaccurate test results involving diseased sheep. However, because the results were determined to be inconclusive, no actual violation was actually committed.''
FINAL REPORT OF THE TESTING OF THE BELGIAN (VERMONT) SHEEP February 27, 2010
(10 YEARS LATER, FOIA, none of the sheep had any TSE at all...tss)
http://foiamadsheepmadrivervalley.blogspot.com/2010/02/final-report-of-testing-of-belgian.html
Thursday, April 24, 2008
RE-FOIA OF DECLARATION OF EXTRAORDINARY EMERGENCY BECAUSE OF AN ATYPICAL T.S.E. OF FOREIGN ORIGIN IN THE UNITED STATES [Docket No. 00-072-1]
http://foiamadsheepmadrivervalley.blogspot.com/2008/04/re-foia-of-declaration-of-extraordinary.html
FOIA MAD SHEEP MAD RIVER VALLEY
Tuesday, November 13, 2007
DECLARATION OF EXTRAORDINARY EMERGENCY BECAUSE OF AN ATYPICAL T.S.E. (PRION DISEASE) OF FOREIGN ORIGIN IN THE UNITED STATES [Docket No. 00-072-1]
To: Garfield.O.Daley@aphis.usda.gov
CC: phyllis.Fong@usda.gov; bse-L@aegee.org;
Re: FOIA APPEAL 07-566 DECLARATION OF EXTRAORDINARY EMERGENCY BECAUSE OF AN ATYPICAL T.S.E. (PRION DISEASE) OF FOREIGN ORIGIN IN THE UNITED STATES [Docket No. 00-072-1]
November 13, 2007
Greetings Garfield O. Daley, Acting FOIA Director, and USDA et al,
SNIP
for those interested, please see full text answer below received from USDA et al below on latest appeal ;
http://foiamadsheepmadrivervalley.blogspot.com/2007/11/declaration-of-extraordinary-emergency.html
http://foiamadsheepmadrivervalley.blogspot.com/
Owens, Julie
From: Terry S. Singeltary Sr. [flounder9@verizon.net]
Sent: Monday. July 24. 2006 1:09 PM
To: FSIS Regulations Comments
Subject: [Docket No. FSIS-2006-0011] FSIS Harvard Risk Assessment of Bovine Spongiform Encephalopathy (BSE)
Greetings FSIS,
I would kindly like to comment on the following :
[Federal Register: July 12, 2006 (Volume 71, Number 133)] (Notices) [Page 39282-39283] From the Federal Register Online via GPO Access [wais.access.gpo.gov] [DOCID:fr12jy06-35] DEPARTMENT OF AGRICULTURE Food Safety and Inspection Service [Docket No. FSIS-2006-0011]
Harvard Risk Assessment of Bovine Spongiform Encephalopathy (BSE)
Update; Notice of Availability and Technical Meeting
AGENCY: Food Safety and Inspection Service, USDA.
ACTION: Notice of availability and announcement of technical meeting. SUMMARY: The Food Safety and Inspection Service (FSIS) is announcing
the availability of an updated risk assessment model and report for BSE. The previous risk assessment, released in October 2003, was revised to incorporate information available through December 2003, including the discovery of a BSE-infected cow in Washington State. The revised risk assessment model evaluates the impact of measures implemented after the discovery of the BSE-positive cow and recommendations made by an international BSE panel. FSIS will also hold a technical meeting to discuss the updated risk assessment model and report.
DATES: The public meeting will be held on July 25, 2006, from 1 p.m. to
https://web.archive.org/web/20060925205531/http://www.fsis.usda.gov/OPPDE/Comments/2006-0011/2006-0011-1.pdf
SCRAPIE TSE Prion USA RAPID RESPONSE URGENT UPDATES DECEMBER 25, 2025
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
APHIS USDA Captive CWD Herds Update by State December 2025 Update
CHRONIC WASTING DISEASE CASES
https://www.aphis.usda.gov/sites/default/files/status-of-captive-herds.pdf
APHIS USDA Captive CWD Herds Update by State December 2025 Update
https://chronic-wasting-disease.blogspot.com/2025/12/aphis-usda-captive-cwd-herds-update-by.html
https://prpsc.proboards.com/thread/187/aphis-captive-herds-update-december
Chronic wasting disease prions in cervids and wild pigs in North America Preliminary Outbreak Assessment DEFRA 26 January 2026
https://assets.publishing.service.gov.uk/media/697a3b013c71d838df6bd413/CWD_Prions_in_Cervids_and_Wild_Pigs_in_North_America.pdf
https://transmissiblespongiformencephalopathy.blogspot.com/2026/01/chronic-wasting-disease-prions-in.html
https://prpsc.proboards.com/thread/201/defra-cervid-pigs-outbreak-assessment
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
***> 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
TUESDAY, SEPTEMBER 30, 2025
USDA EXPLANATORY NOTES ANIMAL AND PLANT HEALTH INSPECTION SERVICE 2025-2014 CHRONIC WASTING DISEASE CWD TSE CERVID
https://chronic-wasting-disease.blogspot.com/2025/09/usda-explanatory-notes-animal-and-plant.html
Texas TPWD Confirms 116 More Cases CWD, Total To Date 1,215 Positives
TPWD CWD Dashboard 1,215 Total Positive Samples
https://experience.arcgis.com/experience/8f6c27330c444a19b4b57beb7ffabb8b/page/Dashboard#data_s=id%3AdataSource_3-1966d773e34-layer-10%3A2
FRIDAY, APRIL 04, 2025
Trucking CWD TSE Prion
Chronic Wasting Disease CWD TSE Prion of Cervid
“CWD spreads among wild populations at a relatively slow rate, limited by the natural home range and dispersed nature of wild animals.”
NOW HOLD YOUR HORSES, Chronic Wasting Disease CWD of Cervid can spread rather swiftly, traveling around 50 MPH, from the back of truck and trailer, and Here in Texas, we call it ‘Trucking CWD’…
Preventive Veterinary Medicine Volume 234, January 2025, 106385
Use of biosecurity practices to prevent chronic wasting disease in Minnesota cervid herds
Vehicles or trailers that entered the farm were used to transport other live cervids, cervid carcasses, or cervid body parts in past 3 years in 64.3 % (95 % CI 46.3–82.3) of larger elk/reindeer herds compared to 13.6 % (95 % CI 4.7–22.4) of smaller deer herds.
Snip…
Identifying the exact pathway of initial CWD transmission to cervid herds is often not possible, in part due to many potential pathways of transmission for the infection, including both direct and indirect contact with infected farmed or wild cervids (Kincheloe et al., 2021). That study identified that transmissions from infected farmed cervids may occur from direct contact with the movement of cervids from one herd to another and from indirect contact with the sharing of equipment, vehicles, clothing, reproductive equipment, and potentially through semen or embryos.
https://www.sciencedirect.com/science/article/abs/pii/S016758772400271X
“Chronic Wasting Disease (CWD) is a fatal neurological disease and can devastate deer populations by silently spreading through direct animal contact and contaminated environments. Without close monitoring, illegal movement of captive deer increases the risk of introducing CWD to areas it is not known to exist, potentially leading to widespread outbreaks which will impact more than just the health of Texas deer.”
https://tpwd.texas.gov/newsmedia/releases/?req=20250227b
Texas Chronic Wasting Disease CWD TSE Prion Dashboard Update August 2025
SEE NEW DASHBOARD FOR CWD POSITIVES!
https://experience.arcgis.com/experience/8f6c27330c444a19b4b57beb7ffabb8b/page/Dashboard#data_s=id%3AdataSource_3-1966d773e34-layer-10%3A29
Texas CWD total by calendar years
https://chronic-wasting-disease.blogspot.com/2024/12/texas-cwd-tse-prion-positive-samples-by.html
https://tpwd.texas.gov/huntwild/wild/diseases/cwd/positive-cases/listing-cwd-cases-texas.phtml#texasCWD
Counties where CWD Exposed Deer were Released
https://tpwd.texas.gov/documents/257/CWD-Trace-OutReleaseSites.pdf
Number of CWD Exposed Deer Released by County
https://tpwd.texas.gov/documents/258/CWD-Trace-OutReleaseSites-NbrDeer.pdf
CWD Status Captive Herds
https://www.aphis.usda.gov/sites/default/files/status-of-captive-herds.pdf
THURSDAY, AUGUST 14, 2025
Texas Game Wardens Near Conclusion of ‘Ghost Deer’ Case with 24 Suspects, 1,400 Charges Filed Statewide
https://chronic-wasting-disease.blogspot.com/2025/08/texas-game-wardens-near-conclusion-of.html
https://prpsc.proboards.com/thread/178/texas-game-wardens-conclusion-ghost
WEDNESDAY, MAY 14, 2025
Texas CWD TSE Prion Cases Rises to 1099 Confirmed Cases To Date
https://chronic-wasting-disease.blogspot.com/2025/05/texas-cwd-tse-prion-cases-rises-to-1099.html
TAHC 425th Commission Meeting CWD 1:45:00
* See CWD speakers expressing their concerns with changed regulations…
2:00 hr mark
https://m.youtube.com/watch?v=bWawHpdn_7I
TEXAS ANIMAL HEALTH COMMISSION 423rd Commission Meeting CWD Update February 25, 2025
https://chronic-wasting-disease.blogspot.com/2025/02/texas-animal-health-commission-423rd.html
So, this is what we leave our children and grandchildren?
Chronic Wasting Disease CWD TSE PrP transmission to, Cattle, Sheep, Pigs, Cervid, Primates, oh my!
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
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
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
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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.”
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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.”
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
Cattle with the E211K polymorphism, and gCJD linked to a glutamic acid to lysine substitution at codon 200 (E200K) of PRNP, what if?
https://creutzfeldt-jakob-disease.blogspot.com/2026/01/cattle-with-e211k-polymorphism-and-gcjd.html
Cattle with the E211K vs Humans E200K of PRNP, what if?
https://prpsc.proboards.com/thread/195/cattle-e211k-humans-e200k-prnp
ARS Research Elucidating the Pathobiology and Transmission of Transmissible Spongiform Encephalopathies 2025 Annual Report
Price of TSE Prion Poker Goes Up Again…terry
https://transmissiblespongiformencephalopathy.blogspot.com/2025/12/ars-research-elucidating-pathobiology.html
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
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
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
https://prpsc.proboards.com/thread/191/neuropsychiatric-symptoms-sporadic-cjd-review
TUESDAY, JULY 13, 2021
Chronic Wasting Disease and the Canadian Agriculture and Agri-food Sectors Current Knowledge Risks and Policy Options
“The science is progressing on the possibility of transmission of CWD to humans through oral transmission, but the complete assessment of this possibility remains to be done.”
https://capi-icpa.ca/wp-content/uploads/2021/07/Chronic-Wasting-Disease_Full-Report_EN.pdf
https://chronic-wasting-disease.blogspot.com/2021/07/chronic-wasting-disease-and-canadian.html
FRIDAY, OCTOBER 31, 2025
Captive Cervid and the Economic Burden of Chronic Wasting Disease CWD TSE Prion?
The economic burden of ignoring CWD would be far greater, imo, with time, if no cervid were left, or just a select few, if the environment/property was so exposed and saturated with CWD, that you couldn’t sell it, you couldn’t grow crops because of the soil saturation of the CWD, water tables saturated with CWD, saturation of hay, grains, from crops uptake on said property, cervid meat saturated from Cervid CWD, remember, You cannot cook the TSE prion disease out of meat, In fact new data now shows that exposure to high temperatures used to cook the meat increased the availability of prions for in vitro amplification. So, what Do we do, how many humans and animals do we continue to expose, continue to saturate with the CWD TSE Prion, …
https://chronic-wasting-disease.blogspot.com/2025/10/captive-cervid-and-economic-burden-of.html
https://prpsc.proboards.com/thread/183/captive-cervid-economic-burden-prion
February 14, 2001
Diagnosis and Reporting of Creutzfeldt-Jakob Disease
Terry S. Singeltary, Sr
Author Affiliations
JAMA. 2001;285(6):733-734. doi:10-1001/pubs.JAMA-ISSN-0098-7484-285-6-jlt0214
To the Editor: In their Research Letter, Dr Gibbons and colleagues1 reported that the annual US death rate due to Creutzfeldt-Jakob disease (CJD) has been stable since 1985. These estimates, however, are based only on reported cases, and do not include misdiagnosed or preclinical cases. It seems to me that misdiagnosis alone would drastically change these figures. An unknown number of persons with a diagnosis of Alzheimer disease in fact may have CJD, although only a small number of these patients receive the postmortem examination necessary to make this diagnosis. Furthermore, only a few states have made CJD reportable. Human and animal transmissible spongiform encephalopathies should be reportable nationwide and internationally.
February 14, 2001
Diagnosis and Reporting of Creutzfeldt-Jakob Disease
Terry S. Singeltary, Sr
Author Affiliations
JAMA. 2001;285(6):733-734. doi:10-1001/pubs.JAMA-ISSN-0098-7484-285-6-jlt0214
https://jamanetwork.com/journals/jama/article-abstract/1031186
2023
https://creutzfeldt-jakob-disease.blogspot.com/2023/09/professor-john-collinge-on-tackling.html
iatrogenic Transmissible Spongiform Encephalopathy, Friendly Fire, Pass It Forward, Unforeseen Circumstances
https://itseprion.blogspot.com/
Chronic Wasting Disease CWD TSE PrP transmission to, Cattle, Sheep, Pigs, Cervid, Primates, oh my!
so, this is what we leave our children and grandchildren???
kind regards, terry
Terry S. Singeltary Sr.
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