Cervid CWD TSE PrP Transmission to Humans, has it already happened and being masked as sporadic CJD, What if? July 2026 Review
Cervid CWD TSE PrP Transmission to Humans, has it already happened and being masked as sporadic CJD, What if? July 2026 Review
A Review
BRIEF RESEARCH REPORT
Public Health, 23 June 2026 Sec. Infectious Diseases: Epidemiology and Prevention Volume 14 - 2026 | https://doi.org/10.3389/fpubh.2026.1847770
Sporadic Creutzfeldt-Jakob disease following venison exposure in a chronic wasting disease-endemic region: a zoonotic surveillance perspective
Eithan Kotkowski .jpeg Eithan Kotkowski 1,2* J Jonathan Trout 1,3 M Matthew Roberts 1,4,5 M Michael Tabet 6 C Carlayne Jackson 1 Sarah Horn .jpeg Sarah Horn 1 1. Department of Neurology, UT Health San Antonio, San Antonio, TX, United States 2. Research Imaging Institute, UT Health San Antonio, San Antonio, TX, United States
Abstract
Background: Creutzfeldt-Jakob disease (CJD) is a rare, rapidly progressive prion disease with established zoonotic transmission only in its variant form. Chronic wasting disease (CWD), a prion disease affecting cervid populations in North America, continues to expand geographically, raising public health concerns regarding potential interspecies transmission.
Methods: We describe the clinical course, diagnostic evaluation, and public health investigation of a patient with confirmed sporadic CJD and long-term venison exposure from CWD-endemic regions in Louisiana. Clinical data, neuroimaging, electroencephalography, cerebrospinal fluid (CSF) biomarkers, neuropathology, and epidemiologic findings were reviewed.
Case report: A 72-year-old lifelong hunter developed rapidly progressive dementia with startle myoclonus and characteristic MRI findings of cortical ribboning and basal ganglia diffusion restriction. CSF biomarkers (RT-QuIC, total tau, 14-3-3) and postmortem neuropathology confirmed sporadic CJD, MM1 subtype. During hospitalization, the patient developed posterior reversible encephalopathy syndrome (PRES), complicating radiographic interpretation. Given extensive cervid exposure and reports of similar illness among hunting peers from the same lodge, the case was reported to public health authorities. Given extensive cervid exposure and reports of similar illness among hunting peers from the same lodge, the apparent clustering of suspected prion disease prompted epidemiologic investigation and public health review.
Conclusion: This case highlights diagnostic and public health challenges posed by prion disease in individuals with relevant zoonotic exposure histories. Although no evidence supporting confirmed CWD-to-human transmission was identified, the apparent clustering of suspected prion disease within a shared exposure network appropriately prompted epidemiologic investigation, structured exposure assessment, and public health review.
snip…
We report a case of confirmed sporadic CJD in a lifelong hunter with extensive venison exposure from CWD-endemic regions in Louisiana, framed as a brief research report emphasizing diagnostic evaluation, exposure assessment, and epidemiologic investigation. Unlike conventional neurology case reports, this report foregrounds the downstream public health response and surveillance implications rather than diagnostic novelty alone.
snip…
Concern for zoonotic transmission arose after the neurology team learned that other individuals from the same hunting lodge had experienced similarly rare neurologic symptoms. Public health investigation identified one additional individual from the lodge with reported positive CSF prion biomarkers but without neuro-pathologic confirmation, precluding definitive classification. This investigation allowed exclusion of alternative neurodegenerative explanations within a suspected cluster and informed appropriate classification within national prion surveillance frameworks. Geographic and temporal analyses supported classification as sporadic CJD.
https://www.frontiersin.org/journals/public-health/articles/10.3389/fpubh.2026.1847770/full
Two Hunters from the Same Lodge Afflicted with Sporadic CJD: Is Chronic Wasting Disease to Blame?
(P7-13.002) Jonathan Trout, Matthew Roberts, Michel Tabet, Eithan Kotkowski, and Sarah HornAUTHORS INFO & AFFILIATIONS April 9, 2024 issue 102 (17_supplement_1) https://doi.org/10.1212/WNL.0000000000204407
Abstract Publication History Information & Authors Metrics & Citations
Methods: We describe the clinical course, diagnostic evaluation, and public health investigation of a patient with confirmed sporadic CJD and long-term venison exposure from CWD-endemic regions in Louisiana. Clinical data, neuroimaging, electroencephalography, cerebrospinal fluid (CSF) biomarkers, neuropathology, and epidemiologic findings were reviewed.
Case report: A 72-year-old lifelong hunter developed rapidly progressive dementia with startle myoclonus and characteristic MRI findings of cortical ribboning and basal ganglia diffusion restriction. CSF biomarkers (RT-QuIC, total tau, 14-3-3) and postmortem neuropathology confirmed sporadic CJD, MM1 subtype. During hospitalization, the patient developed posterior reversible encephalopathy syndrome (PRES), complicating radiographic interpretation. Given extensive cervid exposure and reports of similar illness among hunting peers from the same lodge, the case was reported to public health authorities. Given extensive cervid exposure and reports of similar illness among hunting peers from the same lodge, the apparent clustering of suspected prion disease prompted epidemiologic investigation and public health review.
Conclusion: This case highlights diagnostic and public health challenges posed by prion disease in individuals with relevant zoonotic exposure histories. Although no evidence supporting confirmed CWD-to-human transmission was identified, the apparent clustering of suspected prion disease within a shared exposure network appropriately prompted epidemiologic investigation, structured exposure assessment, and public health review.
snip…
We report a case of confirmed sporadic CJD in a lifelong hunter with extensive venison exposure from CWD-endemic regions in Louisiana, framed as a brief research report emphasizing diagnostic evaluation, exposure assessment, and epidemiologic investigation. Unlike conventional neurology case reports, this report foregrounds the downstream public health response and surveillance implications rather than diagnostic novelty alone.
snip…
Concern for zoonotic transmission arose after the neurology team learned that other individuals from the same hunting lodge had experienced similarly rare neurologic symptoms. Public health investigation identified one additional individual from the lodge with reported positive CSF prion biomarkers but without neuro-pathologic confirmation, precluding definitive classification. This investigation allowed exclusion of alternative neurodegenerative explanations within a suspected cluster and informed appropriate classification within national prion surveillance frameworks. Geographic and temporal analyses supported classification as sporadic CJD.
https://www.frontiersin.org/journals/public-health/articles/10.3389/fpubh.2026.1847770/full
Two Hunters from the Same Lodge Afflicted with Sporadic CJD: Is Chronic Wasting Disease to Blame?
(P7-13.002) Jonathan Trout, Matthew Roberts, Michel Tabet, Eithan Kotkowski, and Sarah HornAUTHORS INFO & AFFILIATIONS April 9, 2024 issue 102 (17_supplement_1) https://doi.org/10.1212/WNL.0000000000204407
Abstract Publication History Information & Authors Metrics & Citations
Abstract
Objective:
This study presents a cluster of Creutzfeldt-Jakob disease (CJD) cases after exposure to chronic wasting disease (CWD)-infected deer, suggestive of potential prion transmission from CWD-infected deer to humans.
Background:
CJD is a rapidly progressive central nervous system disorder caused by misfolded prion proteins. CWD, a prion disease prevalent in North American deer, has raised concerns due to its possible link to CJD. Although no conclusive evidence of cross-species prion transmission exists, vigilance for such cases is crucial for public health.
Design/Methods:
Not applicable.
Results:
In 2022, a 72-year-old man with a history of consuming meat from a CWD-infected deer population presented with rapid-onset confusion and aggression. His friend, who had also eaten venison from the same deer population, recently died of CJD, raising concerns about a potential link between CWD and human prion disease. Despite aggressive symptomatic treatment of seizures and agitation, the patient’s condition deteriorated and he died within a month of initial presentation. The diagnosis was confirmed postmortem as sporadic CJD with homozygous methionine at codon 129 (sCJDMM1). The patient’s history, including a similar case in his social group, suggests a possible novel animal-to-human transmission of CWD. Based on non-human primate and mouse models, cross-species transmission of CJD is plausible. Due to the challenge of distinguishing sCJDMM1 from CWD without detailed prion protein characterization, it is not possible to definitively rule out CWD in these cases. Although causation remains unproven, this cluster emphasizes the need for further investigation into the potential risks of consuming CWD-infected deer and its implications for public health.
Conclusions:
Clusters of sporadic CJD cases may occur in regions with CWD-confirmed deer populations, hinting at potential cross-species prion transmission. Surveillance and further research are essential to better understand this possible association.
Disclosure: Mr. Trout has nothing to disclose. Dr. Roberts has nothing to disclose. Dr. Tabet has nothing to disclose. Dr. Kotkowski has nothing to disclose. Dr. Horn has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Cala Trio. The institution of Dr. Horn has received research support from Alzheimer's Association.
https://www.neurology.org/doi/abs/10.1212/WNL.0000000000204407
TUESDAY, MAY 11, 2021
A Unique Presentation of Creutzfeldt-Jakob Disease in a Patient Consuming Deer Antler Velvet
Conclusion
We believe that our patient’s case of CJD is highly suspicious for cervid etiology given the circumstances of the case as well as the strong evidence of plausibility reported in published literature. This is the first known case of CJD in a patient who had consumed deer antler velvet. Despite the confirmed diagnosis of CJD, a causal relationship between the patient’s disease and his consumption of deer antler velvet cannot be definitively concluded.
Supplemental data including molecular tissue sample analysis and autopsy findings could yield further supporting evidence. Given this patient’s clinical resemblance to CBD and the known histological similarities of CBD with CJD, clinicians should consider both diseases in the differential diagnosis of patients with a similarly esoteric presentation. Regardless of the origin of this patient’s disease, it is clear that the potential for prion transmission from cervids to humans should be further investigated by the academic community with considerable urgency.
https://thescipub.com/pdf/ajidsp.2021.43.48.pdf
''We believe that our patient’s case of CJD is highly suspicious for cervid etiology given the circumstances of the case as well as the strong evidence of plausibility reported in published literature. This is the first known case of CJD in a patient who had consumed deer antler velvet. Despite the confirmed diagnosis of CJD, a causal relationship between the patient’s disease and his consumption of deer antler velvet cannot be definitively concluded.''
https://thescipub.com/pdf/ajidsp.2021.43.48.pdf
CREUTZFELDT JAKOB DISEASE: A Unique Presentation of Creutzfeldt-Jakob Disease in a Patient Consuming Deer Antler Velvet
i was warning England and the BSE Inquiry about just this, way back in 1998, and was ask to supply information to the BSE Inquiry. for anyone that might be interested, see;
Singeltary submission to the BSE Inquiry on CJD and Nutritional Supplements 1998
ABOUT that deer antler spray and CWD TSE PRION... I have been screaming this since my neighbors mom died from cjd, and she had been taking a supplement that contained bovine brain, bovine eyeball, and other SRMs specified risk materials, the most high risk for mad cow disease. just saying...
I made a submission to the BSE Inquiry long ago during the BSE Inquiry days, and they seemed pretty interested.
Sender: "Patricia Cantos"
To: "Terry S Singeltary Sr. (E-mail)"
Subject: Your submission to the Inquiry
Date: Fri, 3 Jul 1998 10:10:05 +0100 3 July 1998
Mr Terry S Singeltary Sr. E-Mail: Flounder at wt.netRef: E2979
Dear Mr Singeltary, Thank you for your E-mail message of the 30th of June 1998 providing the Inquiry with your further comments. Thank you for offering to provide the Inquiry with any test results on the nutritional supplements your mother was taking before she died. As requested I am sending you our general Information Pack and a copy of the Chairman's letter. Please contact me if your system cannot read the attachments. Regarding your question, the Inquiry is looking into many aspects of the scientific evidence on BSE and nvCJD.
I would refer you to the transcripts of evidence we have already heard which are found on our internet site at ;
http://www.bse.org.uk.
Could you please provide the Inquiry with a copy of the press article you refer to in your e-mail? If not an approximate date for the article so that we can locate it? In the meantime, thank you for you comments. Please do not hesitate to contact me on... snip...end...tss
everyone I tell this too gets it screwed up...MY MOTHER WAS NOT TAKING THOSE SUPPLEMENTS IPLEX (that I ever knew of). this was my neighbors mother that died exactly one year previously and to the day of sporadic CJD that was diagnosed as Alzheimer’s at first. my mother died exactly a year later from the Heidenhain Variant of Creutzfeldt Jakob Disease hvCJD, and exceedingly rare strains of the ever growing sporadic CJD’s. both cases confirmed. ...kind regards, terry
2004
Jeff Swann and his Mom, cwd link... sporadic CJD?, CBC NEWS Jeff Schwan sCJD, CWD, and Professor Aguzzi on BSE and sporadic CJD
????: CBCnews
https://histodb15.usz.ch/pages/Images/videos/video-004/video-004.html
2004
April 22, 2004, 10:30 AM CDT
Objective:
This study presents a cluster of Creutzfeldt-Jakob disease (CJD) cases after exposure to chronic wasting disease (CWD)-infected deer, suggestive of potential prion transmission from CWD-infected deer to humans.
Background:
CJD is a rapidly progressive central nervous system disorder caused by misfolded prion proteins. CWD, a prion disease prevalent in North American deer, has raised concerns due to its possible link to CJD. Although no conclusive evidence of cross-species prion transmission exists, vigilance for such cases is crucial for public health.
Design/Methods:
Not applicable.
Results:
In 2022, a 72-year-old man with a history of consuming meat from a CWD-infected deer population presented with rapid-onset confusion and aggression. His friend, who had also eaten venison from the same deer population, recently died of CJD, raising concerns about a potential link between CWD and human prion disease. Despite aggressive symptomatic treatment of seizures and agitation, the patient’s condition deteriorated and he died within a month of initial presentation. The diagnosis was confirmed postmortem as sporadic CJD with homozygous methionine at codon 129 (sCJDMM1). The patient’s history, including a similar case in his social group, suggests a possible novel animal-to-human transmission of CWD. Based on non-human primate and mouse models, cross-species transmission of CJD is plausible. Due to the challenge of distinguishing sCJDMM1 from CWD without detailed prion protein characterization, it is not possible to definitively rule out CWD in these cases. Although causation remains unproven, this cluster emphasizes the need for further investigation into the potential risks of consuming CWD-infected deer and its implications for public health.
Conclusions:
Clusters of sporadic CJD cases may occur in regions with CWD-confirmed deer populations, hinting at potential cross-species prion transmission. Surveillance and further research are essential to better understand this possible association.
Disclosure: Mr. Trout has nothing to disclose. Dr. Roberts has nothing to disclose. Dr. Tabet has nothing to disclose. Dr. Kotkowski has nothing to disclose. Dr. Horn has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Cala Trio. The institution of Dr. Horn has received research support from Alzheimer's Association.
https://www.neurology.org/doi/abs/10.1212/WNL.0000000000204407
TUESDAY, MAY 11, 2021
A Unique Presentation of Creutzfeldt-Jakob Disease in a Patient Consuming Deer Antler Velvet
Conclusion
We believe that our patient’s case of CJD is highly suspicious for cervid etiology given the circumstances of the case as well as the strong evidence of plausibility reported in published literature. This is the first known case of CJD in a patient who had consumed deer antler velvet. Despite the confirmed diagnosis of CJD, a causal relationship between the patient’s disease and his consumption of deer antler velvet cannot be definitively concluded.
Supplemental data including molecular tissue sample analysis and autopsy findings could yield further supporting evidence. Given this patient’s clinical resemblance to CBD and the known histological similarities of CBD with CJD, clinicians should consider both diseases in the differential diagnosis of patients with a similarly esoteric presentation. Regardless of the origin of this patient’s disease, it is clear that the potential for prion transmission from cervids to humans should be further investigated by the academic community with considerable urgency.
https://thescipub.com/pdf/ajidsp.2021.43.48.pdf
''We believe that our patient’s case of CJD is highly suspicious for cervid etiology given the circumstances of the case as well as the strong evidence of plausibility reported in published literature. This is the first known case of CJD in a patient who had consumed deer antler velvet. Despite the confirmed diagnosis of CJD, a causal relationship between the patient’s disease and his consumption of deer antler velvet cannot be definitively concluded.''
https://thescipub.com/pdf/ajidsp.2021.43.48.pdf
CREUTZFELDT JAKOB DISEASE: A Unique Presentation of Creutzfeldt-Jakob Disease in a Patient Consuming Deer Antler Velvet
i was warning England and the BSE Inquiry about just this, way back in 1998, and was ask to supply information to the BSE Inquiry. for anyone that might be interested, see;
Singeltary submission to the BSE Inquiry on CJD and Nutritional Supplements 1998
ABOUT that deer antler spray and CWD TSE PRION... I have been screaming this since my neighbors mom died from cjd, and she had been taking a supplement that contained bovine brain, bovine eyeball, and other SRMs specified risk materials, the most high risk for mad cow disease. just saying...
I made a submission to the BSE Inquiry long ago during the BSE Inquiry days, and they seemed pretty interested.
Sender: "Patricia Cantos"
To: "Terry S Singeltary Sr. (E-mail)"
Subject: Your submission to the Inquiry
Date: Fri, 3 Jul 1998 10:10:05 +0100 3 July 1998
Mr Terry S Singeltary Sr. E-Mail: Flounder at wt.netRef: E2979
Dear Mr Singeltary, Thank you for your E-mail message of the 30th of June 1998 providing the Inquiry with your further comments. Thank you for offering to provide the Inquiry with any test results on the nutritional supplements your mother was taking before she died. As requested I am sending you our general Information Pack and a copy of the Chairman's letter. Please contact me if your system cannot read the attachments. Regarding your question, the Inquiry is looking into many aspects of the scientific evidence on BSE and nvCJD.
I would refer you to the transcripts of evidence we have already heard which are found on our internet site at ;
http://www.bse.org.uk.
Could you please provide the Inquiry with a copy of the press article you refer to in your e-mail? If not an approximate date for the article so that we can locate it? In the meantime, thank you for you comments. Please do not hesitate to contact me on... snip...end...tss
everyone I tell this too gets it screwed up...MY MOTHER WAS NOT TAKING THOSE SUPPLEMENTS IPLEX (that I ever knew of). this was my neighbors mother that died exactly one year previously and to the day of sporadic CJD that was diagnosed as Alzheimer’s at first. my mother died exactly a year later from the Heidenhain Variant of Creutzfeldt Jakob Disease hvCJD, and exceedingly rare strains of the ever growing sporadic CJD’s. both cases confirmed. ...kind regards, terry
2004
Jeff Swann and his Mom, cwd link... sporadic CJD?, CBC NEWS Jeff Schwan sCJD, CWD, and Professor Aguzzi on BSE and sporadic CJD
????: CBCnews
https://histodb15.usz.ch/pages/Images/videos/video-004/video-004.html
2004
April 22, 2004, 10:30 AM CDT
Guests: Patrick Singh, Terry Schwan, Janet Skarbek, Bill Fielding (BEGIN VIDEOTAPE)
ANNOUNCER: DEBORAH NORVILLE TONIGHT.
https://www.nbcnews.com/id/wbna4806886
1997-11-10: Panorama - The British disease
https://histodb15.usz.ch/pages/Images/videos/video-009/video-009.html
July’s Milwaukee Journal Sentinel article
state officials to ask CDC to investigate the cases of the three men who shared wild game feasts.
The two men the CDC is still investigating were 55 and 66 years old. But there’s also Kevin Bass, a Minnesota hunter who ate Barron County venison and died of CJD at 41. And there’s Jeff Schwan, whose Michigan Tech fraternity brothers used to bring venison sausage back to the frat house. His mother, Terry, says that in May 2001, Jeff, 26, began complaining about his vision. A friend noticed misspellings in his e-mail, which was totally unlike him. Jeff be-gan losing weight. He became irritable and withdrawn. By the end of June, he couldn’t remember the four-digit code to open the garage door or when and how to feed his parents’ cats. At a family gathering in July, he stuck to his parents and girlfriend, barely talking. “On the night we took him to the hospital, he was speaking like he was drunk or high and I noticed his pupils were so dilated I couldn’t see the irises,” his mother says. By then, Jeff was no longer able to do even simple things on his computer at work, and “in the hospital, he couldn’t drink enough water.” When he died on September 27, 2001, an autopsy confirmed he had sporadic CJD.
In 2000, Belay looked into three CJD cases reported by The Denver Post, two hunters who ate meat from animals killed in Wyoming and the daughter of a hunter who ate venison from a plant that processed Colorado elk. All three died of CJD before they were 30 years old. The CDC asked the USDA to kill 1,000 deer and elk in the area where the men hunted. Belay and others reported their findings in the Archives of Neurology, writing that although “circumstances suggested a link between the three cases and chronic wasting disease, they could find no ‘causal’ link.” Which means, says Belay, “not a single one of those 1,000 deer tested positive for CWD. For all we know, these cases may be CWD. What we have now doesn’t indicate a connection. That’s reassuring, but it would be wrong to say it will never happen.”
So far, says NIH researcher Race, the two Wisconsin cases pinpointed by the newspaper look like spontaneous CJD. “But we don’t know how CWD would look in human brains. It probably would look like some garden-variety sporadic CJD.”
snip…end
https://www.milwaukeemag.com/TheKillerAmongUs/
DEATHS of three outdoorsmen from brain-destroying illnesses are under investigation 2002 A REVIEW 2023
Subject: LARRY SCHONBERGER & CDC TRYING TO DIGEST THEIR OWN B.S.eee on CWD AND POTENTIAL THREAT TO HUMANS !!!
https://www.nbcnews.com/id/wbna4806886
1997-11-10: Panorama - The British disease
https://histodb15.usz.ch/pages/Images/videos/video-009/video-009.html
July’s Milwaukee Journal Sentinel article
state officials to ask CDC to investigate the cases of the three men who shared wild game feasts.
The two men the CDC is still investigating were 55 and 66 years old. But there’s also Kevin Bass, a Minnesota hunter who ate Barron County venison and died of CJD at 41. And there’s Jeff Schwan, whose Michigan Tech fraternity brothers used to bring venison sausage back to the frat house. His mother, Terry, says that in May 2001, Jeff, 26, began complaining about his vision. A friend noticed misspellings in his e-mail, which was totally unlike him. Jeff be-gan losing weight. He became irritable and withdrawn. By the end of June, he couldn’t remember the four-digit code to open the garage door or when and how to feed his parents’ cats. At a family gathering in July, he stuck to his parents and girlfriend, barely talking. “On the night we took him to the hospital, he was speaking like he was drunk or high and I noticed his pupils were so dilated I couldn’t see the irises,” his mother says. By then, Jeff was no longer able to do even simple things on his computer at work, and “in the hospital, he couldn’t drink enough water.” When he died on September 27, 2001, an autopsy confirmed he had sporadic CJD.
In 2000, Belay looked into three CJD cases reported by The Denver Post, two hunters who ate meat from animals killed in Wyoming and the daughter of a hunter who ate venison from a plant that processed Colorado elk. All three died of CJD before they were 30 years old. The CDC asked the USDA to kill 1,000 deer and elk in the area where the men hunted. Belay and others reported their findings in the Archives of Neurology, writing that although “circumstances suggested a link between the three cases and chronic wasting disease, they could find no ‘causal’ link.” Which means, says Belay, “not a single one of those 1,000 deer tested positive for CWD. For all we know, these cases may be CWD. What we have now doesn’t indicate a connection. That’s reassuring, but it would be wrong to say it will never happen.”
So far, says NIH researcher Race, the two Wisconsin cases pinpointed by the newspaper look like spontaneous CJD. “But we don’t know how CWD would look in human brains. It probably would look like some garden-variety sporadic CJD.”
snip…end
https://www.milwaukeemag.com/TheKillerAmongUs/
DEATHS of three outdoorsmen from brain-destroying illnesses are under investigation 2002 A REVIEW 2023
Subject: LARRY SCHONBERGER & CDC TRYING TO DIGEST THEIR OWN B.S.eee on CWD AND POTENTIAL THREAT TO HUMANS !!!
Date: July 31, 2002 at 7:17 pm
Subject: Deaths of three men probed for link to Wisconsin deer disease
Date: Wed, 31 Jul 2002 18:05:42 -0700
From: "Terry S. Singeltary Sr."
Reply-To: Bovine Spongiform Encephalopathy
To: BSE-L@uni-karlsruhe.de
######## Bovine Spongiform Encephalopathy #########
Deaths of three men probed for link to Wisconsin deer disease Robert Imrie Associated Press
Published Aug 1, 2002
WAUSAU, Wis. -- The deaths of three outdoorsmen from brain-destroying illnesses are under investigation by medical experts who want to know whether chronic wasting disease has crossed from animals into humans, just as mad cow disease did in Europe.
The men knew one another and ate elk and deer meat at wild game feasts hosted by one of them in Wisconsin during the 1980s and '90s. All three died in the 1990s. Two were from Wisconsin; one was from Minnesota. Investigators want to know whether the deaths were just a coincidence or whether the men contracted their diseases from the meat of infected game. There has never been a documented case of a person contracting a brain-destroying illness from eating wild animals with chronic wasting disease.
``We are not saying it absolutely can't happen. We know that it's a mistake to say that,'' said Dr. Larry Schonberger, a specialist at the Centers for Disease Control and Prevention in Atlanta. ``It gets a lot of people scared and it has economic consequences and everything, so we need to check it out.''
In February, chronic wasting disease - an incurable, brain-destroying illness that causes deer, elk, moose and caribou to grow thin and die - was found in Wisconsin deer, marking the first time it was discovered east of the Mississippi River. It was identified in Colorado elk more than three decades ago and is now known to exist in deer or elk in eight states and Canada; thousands of animals are now being slaughtered to contain it.
Chronic wasting disease is related to mad cow disease in cattle and Creutzfeldt-Jakob disease in humans. All three diseases are caused by mutant proteins called prions that make spongelike holes in the brain. During the 1990s, scientists confirmed that people in Europe developed Creutzfeldt-Jakob from eating beef from cattle infected with mad cow disease. The finding devastated Europe's beef industry.
If elk and deer meat prove to be a similar threat, the effects would not be nearly as disastrous, in part because beef eating is far more widespread. But such a finding could raise fears of the disease spreading from wild animals to livestock and endangering the food supply. Also, hunting where the disease is known to exist would drop off dramatically, said Steve Torbit, a National Wildlife Federation biologist. ``It may be possible hunting persists as a way to collect hides or heads and antlers,'' he said. ``It is a rocky ride we are in for.''
The Wisconsin Division of Health and the CDC are looking at autopsy results and other records regarding James Botts, Wayne Waterhouse and Roger Marten. Waterhouse, of Chetek, Wis., and Marten, of Mondovi, Wis., both 66, died in 1993. Botts, 55, of Blaine, Minn., died in 1999. Waterhouse and Marten were avid hunters; Botts fished.
Waterhouse and Botts died of what was diagnosed as Creutzfeldt-Jakob, their families said. Creutzfeldt-Jakob is always fatal and occurs in just one in a million people. Marten died of Pick's disease, a more common brain-destroying disorder, said his son, Randy.
Jeff Davis, the state epidemiologist, said four or five cases of Creutzfeldt-Jakob are diagnosed in Wisconsin each year. What makes the deaths of Waterhouse, Botts and Marten worth investigating is that the men knew one another and attended game feasts that Waterhouse held at his cabin near Superior, Davis said.
Botts' widow, Judy, believes her husband's illness came from the meat he ate at the feasts. She said the gatherings were the only thing the three occasional friends had in common, other than their love of hunting or fishing.
In 1999, a World Health Organization panel concluded there was no scientific evidence that chronic wasting disease can infect humans. But it also said no part of a deer or elk believed to be infected should be eaten.
After years of suspicions, it was not until 1994 that there was enough evidence for scientists to conclude that humans could get a form of mad cow disease from beef.
Dr. G. Richard Olds, chairman of medicine at the Medical College of Wisconsin in Milwaukee, said it is possible scientists could come to same conclusion about chronic wasting disease, though it could take as long as 15 years.
``I am not trying to scare people inappropriately,'' he said. ``But we need to be honest about this situation.''
---
On the Net: National Prion Disease Pathology Surveillance Center: http://www.cjdsurveillance.com
CDC: http://www.cdc.gov
http://www.startribune.com/stories/1556/3131888.html
TSS
=====
From: TSS (216-119-162-17.ipset44.wt.net)
Subject: Re: LARRY SCHONBERGER & CDC [PICK'S DISEASE MY @SS!!!]
Date: August 1, 2002 at 10:25 am PST
In Reply to: LARRY SCHONBERGER & CDC TRYING TO DIGEST THEIR OWN B.S.eee on CWD AND POTENTIAL THREAT TO HUMANS !!!
From: "Terry S. Singeltary Sr."
Reply-To: Bovine Spongiform Encephalopathy
To: BSE-L@uni-karlsruhe.de
######## Bovine Spongiform Encephalopathy #########
Deaths of three men probed for link to Wisconsin deer disease Robert Imrie Associated Press
Published Aug 1, 2002
WAUSAU, Wis. -- The deaths of three outdoorsmen from brain-destroying illnesses are under investigation by medical experts who want to know whether chronic wasting disease has crossed from animals into humans, just as mad cow disease did in Europe.
The men knew one another and ate elk and deer meat at wild game feasts hosted by one of them in Wisconsin during the 1980s and '90s. All three died in the 1990s. Two were from Wisconsin; one was from Minnesota. Investigators want to know whether the deaths were just a coincidence or whether the men contracted their diseases from the meat of infected game. There has never been a documented case of a person contracting a brain-destroying illness from eating wild animals with chronic wasting disease.
``We are not saying it absolutely can't happen. We know that it's a mistake to say that,'' said Dr. Larry Schonberger, a specialist at the Centers for Disease Control and Prevention in Atlanta. ``It gets a lot of people scared and it has economic consequences and everything, so we need to check it out.''
In February, chronic wasting disease - an incurable, brain-destroying illness that causes deer, elk, moose and caribou to grow thin and die - was found in Wisconsin deer, marking the first time it was discovered east of the Mississippi River. It was identified in Colorado elk more than three decades ago and is now known to exist in deer or elk in eight states and Canada; thousands of animals are now being slaughtered to contain it.
Chronic wasting disease is related to mad cow disease in cattle and Creutzfeldt-Jakob disease in humans. All three diseases are caused by mutant proteins called prions that make spongelike holes in the brain. During the 1990s, scientists confirmed that people in Europe developed Creutzfeldt-Jakob from eating beef from cattle infected with mad cow disease. The finding devastated Europe's beef industry.
If elk and deer meat prove to be a similar threat, the effects would not be nearly as disastrous, in part because beef eating is far more widespread. But such a finding could raise fears of the disease spreading from wild animals to livestock and endangering the food supply. Also, hunting where the disease is known to exist would drop off dramatically, said Steve Torbit, a National Wildlife Federation biologist. ``It may be possible hunting persists as a way to collect hides or heads and antlers,'' he said. ``It is a rocky ride we are in for.''
The Wisconsin Division of Health and the CDC are looking at autopsy results and other records regarding James Botts, Wayne Waterhouse and Roger Marten. Waterhouse, of Chetek, Wis., and Marten, of Mondovi, Wis., both 66, died in 1993. Botts, 55, of Blaine, Minn., died in 1999. Waterhouse and Marten were avid hunters; Botts fished.
Waterhouse and Botts died of what was diagnosed as Creutzfeldt-Jakob, their families said. Creutzfeldt-Jakob is always fatal and occurs in just one in a million people. Marten died of Pick's disease, a more common brain-destroying disorder, said his son, Randy.
Jeff Davis, the state epidemiologist, said four or five cases of Creutzfeldt-Jakob are diagnosed in Wisconsin each year. What makes the deaths of Waterhouse, Botts and Marten worth investigating is that the men knew one another and attended game feasts that Waterhouse held at his cabin near Superior, Davis said.
Botts' widow, Judy, believes her husband's illness came from the meat he ate at the feasts. She said the gatherings were the only thing the three occasional friends had in common, other than their love of hunting or fishing.
In 1999, a World Health Organization panel concluded there was no scientific evidence that chronic wasting disease can infect humans. But it also said no part of a deer or elk believed to be infected should be eaten.
After years of suspicions, it was not until 1994 that there was enough evidence for scientists to conclude that humans could get a form of mad cow disease from beef.
Dr. G. Richard Olds, chairman of medicine at the Medical College of Wisconsin in Milwaukee, said it is possible scientists could come to same conclusion about chronic wasting disease, though it could take as long as 15 years.
``I am not trying to scare people inappropriately,'' he said. ``But we need to be honest about this situation.''
---
On the Net: National Prion Disease Pathology Surveillance Center: http://www.cjdsurveillance.com
CDC: http://www.cdc.gov
http://www.startribune.com/stories/1556/3131888.html
TSS
=====
From: TSS (216-119-162-17.ipset44.wt.net)
Subject: Re: LARRY SCHONBERGER & CDC [PICK'S DISEASE MY @SS!!!]
Date: August 1, 2002 at 10:25 am PST
In Reply to: LARRY SCHONBERGER & CDC TRYING TO DIGEST THEIR OWN B.S.eee on CWD AND POTENTIAL THREAT TO HUMANS !!!
posted by TSS on July 31, 2002 at 7:17 pm:
illness that causes deer, elk, moose and caribou to grow thin and die - never been seen in moose or caribou as far as i know. not one animal has been tested though.
Waterhouse and Botts died of what was diagnosed as Creutzfeldt-Jakob,
illness that causes deer, elk, moose and caribou to grow thin and die - never been seen in moose or caribou as far as i know. not one animal has been tested though.
Waterhouse and Botts died of what was diagnosed as Creutzfeldt-Jakob,
>their families said. Creutzfeldt-Jakob is
>always fatal and occurs in
>just one in a million people.
>Marten died of Pick's disease, a more
>common brain-destroying disorder, said his son, Randy.
What can CJD be confused with? Other CNS disorders with focal spongiform change
Alzheimer's disease Pick's disease Diffuse Lewy body disease Dementia of frontal lobe type Dementia in motor neurone disease Panencephalopathic type of CJD with neuropathologic features similar to Pick's disease.
What can CJD be confused with? Other CNS disorders with focal spongiform change
Alzheimer's disease Pick's disease Diffuse Lewy body disease Dementia of frontal lobe type Dementia in motor neurone disease Panencephalopathic type of CJD with neuropathologic features similar to Pick's disease.
Clin Neuropathol 1993 Jan-Feb;12(1):1-6 Pietrini V, Danieli D, Bevilacqua P, Lechi A
The panencephalopathic type of Creutzfeldt-Jakob disease is characterized by a serious degeneration of the white matter in addition to the other pathological features of the classic Creutzfeldt-Jakob disease. The clinical and neuropathological findings of a new case are described in a woman aged 62, who died after a year of illness. The brain appeared seriously affected by atrophy and white matter degeneration. Microscopically, it showed a marked cortical spongiosis, with gemistocytic astrogliosis and degeneration of the white matter of both hemispheres. Although a serious loss of nerve cells was evident, some residual neurons with a ballooned aspect were found in the fronto-temporal cortex. Other neurons presented argyrophilic inclusions similar to Pick bodies.
Nature 393, 698 (1998) M Hutton, et al.
Thirteen families have been described with an autosomal dominantly inherited dementia named frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17), historically termed Pick's disease. Most FTDP-17 cases show neuronal and/or glial inclusions that stain positively with antibodies raised against the microtubule-associated protein Tau, although the Tau pathology varies considerably in both its quantity (or severity) and characteristics. Previous studies have mapped the FTDP-17 locus to a 2-centimorgan region on chromosome 17q21.11; the tau gene also lies within this region. The authors have now sequenced tau in FTDP- 17 families and identified three missense mutations (G272V, P301L and R406W) and three mutations in the 5' splice site of exon 10.
The splice-site mutations all destabilize a potential stem-loop structure which is probably involved in regulating the alternative splicing of exon10. This causes more frequent usage of the 5' splice site and an increased proportion of tau transcripts that include exon 10. The increase in exon 10+ messenger RNA will increase the proportion of Tau containing four microtubule-binding repeats, which is consistent with the neuropathology described in several families with FTDP-17.
Clin Geriatr Med 2001 May;17(2):209-28 Neuropathology of Alzheimer's disease and other dementias. Dickson DW.
Department of Pathology (Neuropathology), Mayo Clinic, Jacksonville, Florida, USA.
Clinical differentiation of neurodegenerative diseases that produce dementia is imprecise. Neuropathology offers the only way to make a definite diagnosis. The CNS autopsy is also important for clinical quality control and for providing tissue that furthers research into these disabling disorders. This brief article summarizes the major neuropathologic features of largely sporadic disorders that present with late-life dementia. The common causes of dementia discussed are Alzheimer's disease, Lewy body disease, and vascular dementia; less common disorders described are dementia lacking distinctive histopathology, Pick's disease, progressive supranuclear palsy, corticobasal degeneration, and Creutzfeldt-Jakob disease.
Publication Types: Review Review, Tutorial PMID: 11375133 [PubMed - indexed for MEDLINE] 2: Neurology 1997 Jan;48(1):119-25
Accuracy of the clinical diagnosis of corticobasal degeneration: a clinicopathologic study.
Litvan I, Agid Y, Goetz C, Jankovic J, Wenning GK, Brandel JP, Lai EC, Verny M, Ray-Chaudhuri K, McKee A, Jellinger K, Pearce RK, Bartko JJ. Neuroepidemiology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892-9130, USA.
The accuracy of the clinical diagnosis of corticobasal degeneration (CBD) is unknown. To determine its diagnostic accuracy, we presented 105 cases with known neuropathologic diagnoses, including CBD (n = 10), progressive supranuclear palsy (PSP, n = 24), Parkinson's disease (n = 15), diffuse Lewy body disease (n = 14), multiple system atrophy (n = 16), postencephalitic parkinsonism (n = 7), Pick's disease (n = 7), Creutzfeldt-Jakob disease (n = 4), Alzheimer's disease (n = 4), vascular parkinsonism (n = 3), and Whipple's disease (n = 1), as clinical vignettes to six neurologists unaware of the autopsy findings. Reliability was measured with the kappa statistics. The neurologists' clinical diagnoses were compared with clinicopathologic diagnoses for sensitivity, specificity, and positive predictive values at first and last clinic visits. The group reliability for the diagnosis of CBD significantly improved from moderate for the first visit (mean = 34 months after onset) to substantial for the last (68 months after onset). For the first visit, mean sensitivity for CBD was low (35%), but specificity was near-perfect (99.6%). For the last visit, mean sensitivity minimally increased (48.3%), and specificity remained stable. False-negative misdiagnoses mainly occurred with PSP. False-positive diagnoses were rare. The extremely low sensitivity of the clinical diagnosis of CBD suggests that this disorder is markedly underdiagnosed. Although the validity of the clinical diagnosis might have been improved if neurologists could have examined these patients, more important is that this disorder was misdiagnosed by the primary neurologists. In our data set, the best predictors for the diagnosis of CBD included limb dystonia, ideomotor apraxia, myoclonus, and asymmetric akinetic-rigid syndrome with late onset of gait or balance disturbances.
TSS
=====
From: TSS (216-119-162-74.ipset44.wt.net)
Subject: MAN WHO HUNTED IN CWD AREA DIES OF CJD !!!
Date: July 11, 2002 at 8:41 am PST
Subject: Man who hunted in CWD area dies of brain disease
Date: Thu, 11 Jul 2002 10:01:58 -0700
From: "Terry S. Singeltary Sr." Reply-To: Bovine Spongiform Encephalopathy
To: BSE-L@uni-karlsruhe.de
######## Bovine Spongiform Encephalopathy #########
Man who hunted in CWD area dies of brain disease
By Lou Kilzer, Rocky Mountain News July 11, 2002
A 63-year-old Thornton man who hunted elk and deer in a Colorado area beset with chronic wasting disease died early Wednesday from a similar human brain disease.
Otto Berns first noticed signs of memory loss in early May. Doctors struggled to find the correct diagnosis, first telling his family that he had suffered a stroke.
After his condition worsened, Berns' daughter, Nicki, told doctors her father was an avid venison eater who hunted north of Fort Collins. She said she suspected he was suffering some form of CJD, or Creutzfeldt-Jacob disease. In June, a biopsy confirmed her suspicions. Like chronic wasting disease affecting deer and elk in northeast Colorado, CJD is caused by mutant proteins called prions.
Scientists say there is no proof that humans can get CJD from eating infected deer or elk. However, research has begun to see how strong the "species barrier" is.
Nicki Berns said she suspects that her father got the disease from eating game, and that a state health worker said she and her family cannot donate blood.
One way to help answer the question would be to have an autopsy. However, Nicki Berns said her mother declined to allow it, citing a promise she made to her husband.
Berns married his wife, Barbara, Feb. 19, 1966. They moved to Thornton in 1995.
He is also survived by four children - Nicki, William and Ronald Berns of Thornton, and Jim Berns of Pelican Lake, Wisc., and two grandchildren. The family plans private services on Friday.
kilzerl@RockyMountainNews.com or (303) 892-2644
http://www.rockymountainnews.com/drmn/state/article/0,1299,DRMN_21_1258706,00.html
TSS
########### http://mailhost.rz.uni-karlsruhe.de/warc/bse-l.html ############
Exposure Risk of Chronic Wasting Disease in Humans
by Satish K. Nemani 1,2,Jennifer L. Myskiw 3,4,Lise Lamoureux 3,Stephanie A. Booth 3,4 andValerie L. Sim 1,2,*OrcID
1 Centre for Prions and Protein Folding Diseases, Edmonton, AB T6G 2R3, Canada
2 Department of Medicine, Division of Neurology, University of Alberta, Edmonton, AB T6G 2R3, Canada
3 Zoonotic Diseases and Special Pathogens, Public Health Agency of Canada, National Microbiology Laboratory, Winnipeg, MB R3E 3R2, Canada
4 Department of Medical Microbiology and Infectious Diseases, Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3E 3R2, Canada
* Author to whom correspondence should be addressed. Academic Editor: Byron Caughey Viruses 2020, 12(12), 1454; https://doi.org/10.3390/v12121454 Received: 1 December 2020 / Revised: 14 December 2020 / Accepted: 15 December 2020 / Published: 17 December 2020 (This article belongs to the Special Issue The Future of the Chronic Wasting Disease Epizootic) View Full-Text Download PDF Browse Figures Review Reports Cite This Paper
Abstract
The majority of human prion diseases are sporadic, but acquired disease can occur, as seen with variant Creutzfeldt–Jakob disease (vCJD) following consumption of bovine spongiform encephalopathy (BSE). With increasing rates of cervid chronic wasting disease (CWD), there is concern that a new form of human prion disease may arise. Currently, there is no evidence of transmission of CWD to humans, suggesting the presence of a strong species barrier; however, in vitro and in vivo studies on the zoonotic potential of CWD have yielded mixed results. The emergence of different CWD strains is also concerning, as different strains can have different abilities to cross species barriers. Given that venison consumption is common in areas where CWD rates are on the rise, increased rates of human exposure are inevitable. If CWD was to infect humans, it is unclear how it would present clinically; in vCJD, it was strain-typing of vCJD prions that proved the causal link to BSE. Therefore, the best way to screen for CWD in humans is to have thorough strain-typing of harvested cervids and human CJD cases so that we will be in a position to detect atypical strains or strain shifts within the human CJD population.
View Full-Text
Keywords: chronic wasting disease (CWD); zoonotic potential; bovine spongiform encephalopathy (BSE); variant Creutzfeldt–Jakob disease (vCJD); sporadic CJD; CWD prions (PrPCWD); proteinase K resistant prion protein (PK-resPrP); strains; PRNP polymorphism; 129M/V polymorphism
snip...
5.3. Human Data There are no documented case reports of CWD transmission to humans.
The largest exposure occurred at a sportsman feast in Oneida county, NY, where 200 people were unknowingly exposed to CWD-infected venison meat. No cases of CJD were reported after 6 years of follow-up with 81 participants [73]. Six-year follow-up of a point-source exposure to CWD contaminated venison in an Upstate New York community: Risk behaviours and health outcomes 2005–2011. Public Health 2014, 128, 860–868.
Other reports have tried to link cases of CJD with venison exposure, but proof of exposure to CWD is lacking in most cases. From 1997 to 1990, there were reports on the deaths of three unusually young people diagnosed with CJD who had a history of regular consumption of deer or elk meat [74].
Subsequently there were reports on the diagnosis of CJD in hunters who participated in wild game feast in Wisconsin (CDC 2003 report), detection of CJD in Colorado in a 52-year-old woman who had a CWD laboratory exposure, and a 25-year-old man with CJD who had consumed venison meat in a CWD endemic area [75]. In all the above studies, patients had PRNP genotypes, PrPD biochemical characteristics and pathologies suggestive of sporadic CJD. A subsequent study from Colorado demonstrated no statistically significant increase in CJD cases within CWD-endemic areas [76].
snip...see full text;
https://www.mdpi.com/1999-4915/12/12/1454
The largest exposure occurred at a sportsman feast in Oneida county, NY, where 200 people were unknowingly exposed to CWD-infected venison meat. No cases of CJD were reported after 6 years of follow-up with 81 participants [73]. Six-year follow-up of a point-source exposure to CWD contaminated venison in an Upstate New York community: Risk behaviours and health outcomes 2005–2011. Public Health 2014, 128, 860–868...
A FURTHER REVEIW OF THIS SHOWS THAT ACTUALLY THERE WERE MEN THAT PARTICIPATED IN THIS FEAST THAT DID DIE OF A TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY TSE PRION DISEASE, 3 MEN THAT WERE REPORTED, YOU CAN SEE THIS HERE;
Fatal Degenerative Neurologic Illnesses in Men Who Participated in Wild Game Feasts --- Wisconsin, 2002
Creutzfeldt-Jakob disease (CJD) is a fatal neurologic disorder in humans. CJD is one of a group of conditions known as transmissible spongiform encephalopathies (TSEs), or prion diseases, that are believed to be caused by abnormally configured, host-encoded prion proteins that accumulate in the central nervous tissue
(1). CJD has an annual incidence of approximately 1 case per million population in the United States (1) and occurs in three forms: sporadic, genetically determined, and acquired by infection. In the latter form, the incubation period is measured typically in years. Recent evidence that prion infection can cross the species barrier between humans and cattle has raised increasing public health concerns about the possible transmission to humans of a TSE among deer and elk known as chronic wasting disease (CWD)
(2). During 1993--1999, three men who participated in wild game feasts in northern Wisconsin died of degenerative neurologic illnesses. This report documents the investigation of these deaths, which was initiated in August 2002 and which confirmed the death of only one person from CJD. Although no association between CWD and CJD was found, continued surveillance of both diseases remains important to assess the possible risk for CWD transmission to humans.
Case Reports
Case 1. In December 1992, a Wisconsin man aged 66 years with a history of seizures since 1969 sought treatment for recurring seizures, increasing forgetfulness, and worsening hand tremors. Electroencephalographic (EEG) examination demonstrated focal epileptiform activity and nonspecific diffuse abnormalities, but no specific diagnosis was made. In February 1993, he was hospitalized for increasing confusion, ataxia, and movement tremors of his extremities. A magnetic resonance image (MRI) demonstrated mild, nonspecific enhancement along the inferior parasagittal occipital lobe. A repeat EEG showed bifrontal intermittent, short-interval, periodic sharp waves, suggesting a progressive encephalopathy; a diagnosis of CJD was suspected. The man died later that month; neuropathologic examination of brain tissue during autopsy indicated subacute spongiform encephalopathy, compatible with CJD.
The man was a lifelong hunter who ate venison frequently. He hunted primarily in northern Wisconsin but also at least once in Montana. He hosted wild game feasts at his cabin in northern Wisconsin from 1976 until shortly before his death. Fixed brain tissue obtained during the autopsy was sent for analysis to the National Prion Disease Pathology Surveillance Center (NPDPSC) and reexamined at the institution where the autopsy was conducted. Histopathologic examination did not substantiate the diagnosis of prion disease. In addition, 27 brain tissue sections were negative for prions by immunostaining despite positive antibody reactions against other proteins (controls), which indicated that other epitopes in the tissue samples were preserved.
Case 2. In May 1999, a Minnesota man aged 55 years with no previous history of a neurologic disease sought evaluation and treatment following a 3-month history of progressive difficulty in writing and unsteadiness of gait. A computerized tomography (CT) scan and MRI examination of his head did not indicate any abnormality. In June 1999, he was hospitalized following onset of dementia, speech abnormalities, and myoclonic jerking. An EEG indicated left-hemispheric periodic sharp waves and moderate generalized background slowing; CJD was diagnosed clinically. In July 1999, following worsening symptoms and development of right upper extremity dystonia, the patient died. Neuropathologic evaluation of brain tissue during autopsy demonstrated widespread subcortical spongiform lesions, consistent with CJD.
The man was not a hunter but had a history of eating venison. He made an estimated 12 visits to the cabin where the wild game feasts were held, but he participated in only one feast during the mid-1980s. Sections of fixed and frozen brain tissue obtained during autopsy were analyzed at NPDPSC, and prion disease was confirmed by immunohistochemical and Western blot testing. The Western blot characteristics and prion disease phenotype in this patient were consistent with the most common form of sporadic CJD, classified as M/M (M/V) 1 (3). Subsequent genetic typing confirmed the presence of methionine homozygosity (M/M) at codon 129 of the patient's prion protein gene.
Case 3. In June 1992, a Wisconsin man aged 65 years sought treatment for progressive slowing of speech, worsening memory, and personality changes. By January 1993, his speech was reduced to one-word utterances. Neurologic examination showed a flat affect, decreased reflexes, and apraxia. A CT head scan showed mild atrophy, and an EEG was normal. Pick's disease was diagnosed. By May, he was unable to perform any daily living activities; he died in August 1993. Neuropathologic evaluation of brain tissue during autopsy showed symmetrical frontal lobe cerebral cortical atrophy and mild temporal lobe atrophy. No Pick's bodies or spongiform lesions were observed.
The man had a history of eating venison and participated regularly in wild game feasts held at the cabin owned by patient 1. He was a lifelong hunter and hunted mostly in Wisconsin but also in Wyoming and British Columbia. No game was brought to the wild game feasts from his hunting trips outside of Wisconsin. Examination of fixed brain tissue sent to NPDPSC demonstrated no lesions indicative of CJD, and immunohistochemical testing with antibody to the prion protein did not demonstrate the granular deposits seen in prion diseases.
https://www.cdc.gov/mmwr/preview/mmwrhtml/mm5207a1.htm
The man whose disease was found to be CJD was a Minnesotan who died in 1999, the report says. He had visited the Wisconsin cabin about a dozen times but had eaten wild game only once. Analysis of his brain tissue suggested that his disease was the most common form of sporadic CJD, "without apparent unusual neruopathologic or molecular characteristics that might occur if the prion related to CWD had been responsible for the disease," the CDC said.
https://www.cidrap.umn.edu/news-perspective/2003/02/cdc-finds-no-cwd-cjd-link-wisconsin-deaths
SATURDAY, FEBRUARY 23, 2019
Chronic Wasting Disease CWD TSE Prion and THE FEAST 2003 CDC an updated review of the science 2019
https://chronic-wasting-disease.blogspot.com/2019/02/chronic-wasting-disease-cwd-tse-prion.html
TUESDAY, NOVEMBER 04, 2014
Six-year follow-up of a point-source exposure to CWD contaminated venison in an Upstate New York community: risk behaviours and health outcomes 2005–2011
Authors, though, acknowledged the study was limited in geography and sample size and so it couldn't draw a conclusion about the risk to humans. They recommended more study.
The panencephalopathic type of Creutzfeldt-Jakob disease is characterized by a serious degeneration of the white matter in addition to the other pathological features of the classic Creutzfeldt-Jakob disease. The clinical and neuropathological findings of a new case are described in a woman aged 62, who died after a year of illness. The brain appeared seriously affected by atrophy and white matter degeneration. Microscopically, it showed a marked cortical spongiosis, with gemistocytic astrogliosis and degeneration of the white matter of both hemispheres. Although a serious loss of nerve cells was evident, some residual neurons with a ballooned aspect were found in the fronto-temporal cortex. Other neurons presented argyrophilic inclusions similar to Pick bodies.
Nature 393, 698 (1998) M Hutton, et al.
Thirteen families have been described with an autosomal dominantly inherited dementia named frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17), historically termed Pick's disease. Most FTDP-17 cases show neuronal and/or glial inclusions that stain positively with antibodies raised against the microtubule-associated protein Tau, although the Tau pathology varies considerably in both its quantity (or severity) and characteristics. Previous studies have mapped the FTDP-17 locus to a 2-centimorgan region on chromosome 17q21.11; the tau gene also lies within this region. The authors have now sequenced tau in FTDP- 17 families and identified three missense mutations (G272V, P301L and R406W) and three mutations in the 5' splice site of exon 10.
The splice-site mutations all destabilize a potential stem-loop structure which is probably involved in regulating the alternative splicing of exon10. This causes more frequent usage of the 5' splice site and an increased proportion of tau transcripts that include exon 10. The increase in exon 10+ messenger RNA will increase the proportion of Tau containing four microtubule-binding repeats, which is consistent with the neuropathology described in several families with FTDP-17.
Clin Geriatr Med 2001 May;17(2):209-28 Neuropathology of Alzheimer's disease and other dementias. Dickson DW.
Department of Pathology (Neuropathology), Mayo Clinic, Jacksonville, Florida, USA.
Clinical differentiation of neurodegenerative diseases that produce dementia is imprecise. Neuropathology offers the only way to make a definite diagnosis. The CNS autopsy is also important for clinical quality control and for providing tissue that furthers research into these disabling disorders. This brief article summarizes the major neuropathologic features of largely sporadic disorders that present with late-life dementia. The common causes of dementia discussed are Alzheimer's disease, Lewy body disease, and vascular dementia; less common disorders described are dementia lacking distinctive histopathology, Pick's disease, progressive supranuclear palsy, corticobasal degeneration, and Creutzfeldt-Jakob disease.
Publication Types: Review Review, Tutorial PMID: 11375133 [PubMed - indexed for MEDLINE] 2: Neurology 1997 Jan;48(1):119-25
Accuracy of the clinical diagnosis of corticobasal degeneration: a clinicopathologic study.
Litvan I, Agid Y, Goetz C, Jankovic J, Wenning GK, Brandel JP, Lai EC, Verny M, Ray-Chaudhuri K, McKee A, Jellinger K, Pearce RK, Bartko JJ. Neuroepidemiology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892-9130, USA.
The accuracy of the clinical diagnosis of corticobasal degeneration (CBD) is unknown. To determine its diagnostic accuracy, we presented 105 cases with known neuropathologic diagnoses, including CBD (n = 10), progressive supranuclear palsy (PSP, n = 24), Parkinson's disease (n = 15), diffuse Lewy body disease (n = 14), multiple system atrophy (n = 16), postencephalitic parkinsonism (n = 7), Pick's disease (n = 7), Creutzfeldt-Jakob disease (n = 4), Alzheimer's disease (n = 4), vascular parkinsonism (n = 3), and Whipple's disease (n = 1), as clinical vignettes to six neurologists unaware of the autopsy findings. Reliability was measured with the kappa statistics. The neurologists' clinical diagnoses were compared with clinicopathologic diagnoses for sensitivity, specificity, and positive predictive values at first and last clinic visits. The group reliability for the diagnosis of CBD significantly improved from moderate for the first visit (mean = 34 months after onset) to substantial for the last (68 months after onset). For the first visit, mean sensitivity for CBD was low (35%), but specificity was near-perfect (99.6%). For the last visit, mean sensitivity minimally increased (48.3%), and specificity remained stable. False-negative misdiagnoses mainly occurred with PSP. False-positive diagnoses were rare. The extremely low sensitivity of the clinical diagnosis of CBD suggests that this disorder is markedly underdiagnosed. Although the validity of the clinical diagnosis might have been improved if neurologists could have examined these patients, more important is that this disorder was misdiagnosed by the primary neurologists. In our data set, the best predictors for the diagnosis of CBD included limb dystonia, ideomotor apraxia, myoclonus, and asymmetric akinetic-rigid syndrome with late onset of gait or balance disturbances.
TSS
=====
From: TSS (216-119-162-74.ipset44.wt.net)
Subject: MAN WHO HUNTED IN CWD AREA DIES OF CJD !!!
Date: July 11, 2002 at 8:41 am PST
Subject: Man who hunted in CWD area dies of brain disease
Date: Thu, 11 Jul 2002 10:01:58 -0700
From: "Terry S. Singeltary Sr." Reply-To: Bovine Spongiform Encephalopathy
To: BSE-L@uni-karlsruhe.de
######## Bovine Spongiform Encephalopathy #########
Man who hunted in CWD area dies of brain disease
By Lou Kilzer, Rocky Mountain News July 11, 2002
A 63-year-old Thornton man who hunted elk and deer in a Colorado area beset with chronic wasting disease died early Wednesday from a similar human brain disease.
Otto Berns first noticed signs of memory loss in early May. Doctors struggled to find the correct diagnosis, first telling his family that he had suffered a stroke.
After his condition worsened, Berns' daughter, Nicki, told doctors her father was an avid venison eater who hunted north of Fort Collins. She said she suspected he was suffering some form of CJD, or Creutzfeldt-Jacob disease. In June, a biopsy confirmed her suspicions. Like chronic wasting disease affecting deer and elk in northeast Colorado, CJD is caused by mutant proteins called prions.
Scientists say there is no proof that humans can get CJD from eating infected deer or elk. However, research has begun to see how strong the "species barrier" is.
Nicki Berns said she suspects that her father got the disease from eating game, and that a state health worker said she and her family cannot donate blood.
One way to help answer the question would be to have an autopsy. However, Nicki Berns said her mother declined to allow it, citing a promise she made to her husband.
Berns married his wife, Barbara, Feb. 19, 1966. They moved to Thornton in 1995.
He is also survived by four children - Nicki, William and Ronald Berns of Thornton, and Jim Berns of Pelican Lake, Wisc., and two grandchildren. The family plans private services on Friday.
kilzerl@RockyMountainNews.com or (303) 892-2644
http://www.rockymountainnews.com/drmn/state/article/0,1299,DRMN_21_1258706,00.html
TSS
########### http://mailhost.rz.uni-karlsruhe.de/warc/bse-l.html ############
Exposure Risk of Chronic Wasting Disease in Humans
by Satish K. Nemani 1,2,Jennifer L. Myskiw 3,4,Lise Lamoureux 3,Stephanie A. Booth 3,4 andValerie L. Sim 1,2,*OrcID
1 Centre for Prions and Protein Folding Diseases, Edmonton, AB T6G 2R3, Canada
2 Department of Medicine, Division of Neurology, University of Alberta, Edmonton, AB T6G 2R3, Canada
3 Zoonotic Diseases and Special Pathogens, Public Health Agency of Canada, National Microbiology Laboratory, Winnipeg, MB R3E 3R2, Canada
4 Department of Medical Microbiology and Infectious Diseases, Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3E 3R2, Canada
* Author to whom correspondence should be addressed. Academic Editor: Byron Caughey Viruses 2020, 12(12), 1454; https://doi.org/10.3390/v12121454 Received: 1 December 2020 / Revised: 14 December 2020 / Accepted: 15 December 2020 / Published: 17 December 2020 (This article belongs to the Special Issue The Future of the Chronic Wasting Disease Epizootic) View Full-Text Download PDF Browse Figures Review Reports Cite This Paper
Abstract
The majority of human prion diseases are sporadic, but acquired disease can occur, as seen with variant Creutzfeldt–Jakob disease (vCJD) following consumption of bovine spongiform encephalopathy (BSE). With increasing rates of cervid chronic wasting disease (CWD), there is concern that a new form of human prion disease may arise. Currently, there is no evidence of transmission of CWD to humans, suggesting the presence of a strong species barrier; however, in vitro and in vivo studies on the zoonotic potential of CWD have yielded mixed results. The emergence of different CWD strains is also concerning, as different strains can have different abilities to cross species barriers. Given that venison consumption is common in areas where CWD rates are on the rise, increased rates of human exposure are inevitable. If CWD was to infect humans, it is unclear how it would present clinically; in vCJD, it was strain-typing of vCJD prions that proved the causal link to BSE. Therefore, the best way to screen for CWD in humans is to have thorough strain-typing of harvested cervids and human CJD cases so that we will be in a position to detect atypical strains or strain shifts within the human CJD population.
View Full-Text
Keywords: chronic wasting disease (CWD); zoonotic potential; bovine spongiform encephalopathy (BSE); variant Creutzfeldt–Jakob disease (vCJD); sporadic CJD; CWD prions (PrPCWD); proteinase K resistant prion protein (PK-resPrP); strains; PRNP polymorphism; 129M/V polymorphism
snip...
5.3. Human Data There are no documented case reports of CWD transmission to humans.
The largest exposure occurred at a sportsman feast in Oneida county, NY, where 200 people were unknowingly exposed to CWD-infected venison meat. No cases of CJD were reported after 6 years of follow-up with 81 participants [73]. Six-year follow-up of a point-source exposure to CWD contaminated venison in an Upstate New York community: Risk behaviours and health outcomes 2005–2011. Public Health 2014, 128, 860–868.
Other reports have tried to link cases of CJD with venison exposure, but proof of exposure to CWD is lacking in most cases. From 1997 to 1990, there were reports on the deaths of three unusually young people diagnosed with CJD who had a history of regular consumption of deer or elk meat [74].
Subsequently there were reports on the diagnosis of CJD in hunters who participated in wild game feast in Wisconsin (CDC 2003 report), detection of CJD in Colorado in a 52-year-old woman who had a CWD laboratory exposure, and a 25-year-old man with CJD who had consumed venison meat in a CWD endemic area [75]. In all the above studies, patients had PRNP genotypes, PrPD biochemical characteristics and pathologies suggestive of sporadic CJD. A subsequent study from Colorado demonstrated no statistically significant increase in CJD cases within CWD-endemic areas [76].
snip...see full text;
https://www.mdpi.com/1999-4915/12/12/1454
The largest exposure occurred at a sportsman feast in Oneida county, NY, where 200 people were unknowingly exposed to CWD-infected venison meat. No cases of CJD were reported after 6 years of follow-up with 81 participants [73]. Six-year follow-up of a point-source exposure to CWD contaminated venison in an Upstate New York community: Risk behaviours and health outcomes 2005–2011. Public Health 2014, 128, 860–868...
A FURTHER REVEIW OF THIS SHOWS THAT ACTUALLY THERE WERE MEN THAT PARTICIPATED IN THIS FEAST THAT DID DIE OF A TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY TSE PRION DISEASE, 3 MEN THAT WERE REPORTED, YOU CAN SEE THIS HERE;
Fatal Degenerative Neurologic Illnesses in Men Who Participated in Wild Game Feasts --- Wisconsin, 2002
Creutzfeldt-Jakob disease (CJD) is a fatal neurologic disorder in humans. CJD is one of a group of conditions known as transmissible spongiform encephalopathies (TSEs), or prion diseases, that are believed to be caused by abnormally configured, host-encoded prion proteins that accumulate in the central nervous tissue
(1). CJD has an annual incidence of approximately 1 case per million population in the United States (1) and occurs in three forms: sporadic, genetically determined, and acquired by infection. In the latter form, the incubation period is measured typically in years. Recent evidence that prion infection can cross the species barrier between humans and cattle has raised increasing public health concerns about the possible transmission to humans of a TSE among deer and elk known as chronic wasting disease (CWD)
(2). During 1993--1999, three men who participated in wild game feasts in northern Wisconsin died of degenerative neurologic illnesses. This report documents the investigation of these deaths, which was initiated in August 2002 and which confirmed the death of only one person from CJD. Although no association between CWD and CJD was found, continued surveillance of both diseases remains important to assess the possible risk for CWD transmission to humans.
Case Reports
Case 1. In December 1992, a Wisconsin man aged 66 years with a history of seizures since 1969 sought treatment for recurring seizures, increasing forgetfulness, and worsening hand tremors. Electroencephalographic (EEG) examination demonstrated focal epileptiform activity and nonspecific diffuse abnormalities, but no specific diagnosis was made. In February 1993, he was hospitalized for increasing confusion, ataxia, and movement tremors of his extremities. A magnetic resonance image (MRI) demonstrated mild, nonspecific enhancement along the inferior parasagittal occipital lobe. A repeat EEG showed bifrontal intermittent, short-interval, periodic sharp waves, suggesting a progressive encephalopathy; a diagnosis of CJD was suspected. The man died later that month; neuropathologic examination of brain tissue during autopsy indicated subacute spongiform encephalopathy, compatible with CJD.
The man was a lifelong hunter who ate venison frequently. He hunted primarily in northern Wisconsin but also at least once in Montana. He hosted wild game feasts at his cabin in northern Wisconsin from 1976 until shortly before his death. Fixed brain tissue obtained during the autopsy was sent for analysis to the National Prion Disease Pathology Surveillance Center (NPDPSC) and reexamined at the institution where the autopsy was conducted. Histopathologic examination did not substantiate the diagnosis of prion disease. In addition, 27 brain tissue sections were negative for prions by immunostaining despite positive antibody reactions against other proteins (controls), which indicated that other epitopes in the tissue samples were preserved.
Case 2. In May 1999, a Minnesota man aged 55 years with no previous history of a neurologic disease sought evaluation and treatment following a 3-month history of progressive difficulty in writing and unsteadiness of gait. A computerized tomography (CT) scan and MRI examination of his head did not indicate any abnormality. In June 1999, he was hospitalized following onset of dementia, speech abnormalities, and myoclonic jerking. An EEG indicated left-hemispheric periodic sharp waves and moderate generalized background slowing; CJD was diagnosed clinically. In July 1999, following worsening symptoms and development of right upper extremity dystonia, the patient died. Neuropathologic evaluation of brain tissue during autopsy demonstrated widespread subcortical spongiform lesions, consistent with CJD.
The man was not a hunter but had a history of eating venison. He made an estimated 12 visits to the cabin where the wild game feasts were held, but he participated in only one feast during the mid-1980s. Sections of fixed and frozen brain tissue obtained during autopsy were analyzed at NPDPSC, and prion disease was confirmed by immunohistochemical and Western blot testing. The Western blot characteristics and prion disease phenotype in this patient were consistent with the most common form of sporadic CJD, classified as M/M (M/V) 1 (3). Subsequent genetic typing confirmed the presence of methionine homozygosity (M/M) at codon 129 of the patient's prion protein gene.
Case 3. In June 1992, a Wisconsin man aged 65 years sought treatment for progressive slowing of speech, worsening memory, and personality changes. By January 1993, his speech was reduced to one-word utterances. Neurologic examination showed a flat affect, decreased reflexes, and apraxia. A CT head scan showed mild atrophy, and an EEG was normal. Pick's disease was diagnosed. By May, he was unable to perform any daily living activities; he died in August 1993. Neuropathologic evaluation of brain tissue during autopsy showed symmetrical frontal lobe cerebral cortical atrophy and mild temporal lobe atrophy. No Pick's bodies or spongiform lesions were observed.
The man had a history of eating venison and participated regularly in wild game feasts held at the cabin owned by patient 1. He was a lifelong hunter and hunted mostly in Wisconsin but also in Wyoming and British Columbia. No game was brought to the wild game feasts from his hunting trips outside of Wisconsin. Examination of fixed brain tissue sent to NPDPSC demonstrated no lesions indicative of CJD, and immunohistochemical testing with antibody to the prion protein did not demonstrate the granular deposits seen in prion diseases.
https://www.cdc.gov/mmwr/preview/mmwrhtml/mm5207a1.htm
The man whose disease was found to be CJD was a Minnesotan who died in 1999, the report says. He had visited the Wisconsin cabin about a dozen times but had eaten wild game only once. Analysis of his brain tissue suggested that his disease was the most common form of sporadic CJD, "without apparent unusual neruopathologic or molecular characteristics that might occur if the prion related to CWD had been responsible for the disease," the CDC said.
https://www.cidrap.umn.edu/news-perspective/2003/02/cdc-finds-no-cwd-cjd-link-wisconsin-deaths
SATURDAY, FEBRUARY 23, 2019
Chronic Wasting Disease CWD TSE Prion and THE FEAST 2003 CDC an updated review of the science 2019
https://chronic-wasting-disease.blogspot.com/2019/02/chronic-wasting-disease-cwd-tse-prion.html
TUESDAY, NOVEMBER 04, 2014
Six-year follow-up of a point-source exposure to CWD contaminated venison in an Upstate New York community: risk behaviours and health outcomes 2005–2011
Authors, though, acknowledged the study was limited in geography and sample size and so it couldn't draw a conclusion about the risk to humans. They recommended more study.
***>Dr. Ermias Belay was the report's principal author but he said New York and Oneida County officials are following the proper course by not launching a study. "There's really nothing to monitor presently. No one's sick," Belay said, noting the disease's incubation period in deer and elk is measured in years. "
http://chronic-wasting-disease.blogspot.com/2014/11/six-year-follow-up-of-point-source.html
http://chronic-wasting-disease.blogspot.com/2014/11/six-year-follow-up-of-point-source.html
***>Dr. Ermias Belay was the report's principal author but he said New York and Oneida County officials are following the proper course by not launching a study. "There's really nothing to monitor presently. No one's sick," Belay said, noting the disease's incubation period in deer and elk is measured in years. "<***
“In particular the US data do not clearly exclude the possibility of human (sporadic or familial) TSE development due to consumption of venison.”
EFSA
8. Even though human TSE‐exposure risk through consumption of game from European cervids can be assumed to be minor, if at all existing, no final conclusion can be drawn due to the overall lack of scientific data.
In particular the US data do not clearly exclude the possibility of human (sporadic or familial) TSE development due to consumption of venison.
The Working Group thus recognizes a potential risk to consumers if a TSE would be present in European cervids. It might be prudent considering appropriate measures to reduce such a risk, e.g. excluding tissues such as CNS and lymphoid tissues from the human food chain, which would greatly reduce any potential risk for consumers. However, it is stressed that currently, no data regarding a risk of TSE infections from cervid products are available.
“In particular the US data do not clearly exclude the possibility of human (sporadic or familial) TSE development due to consumption of venison.”
***> CWD to Primates and Humans, what if?
“Also, we do not claim that "no-one has ever been infected with prion disease from eating venison." Our conclusion stating that we found no strong evidence of CWD transmission to humans in the article you quoted or in any other forum is limited to the patients we investigated.”
*** now, let’s see what the authors said about this casual link, personal communications years ago, and then the latest on the zoonotic potential from CWD to humans from the TOKYO PRION 2016 CONFERENCE.
see where it is stated NO STRONG evidence. so, does this mean there IS casual evidence ????
“Our conclusion stating that we found no strong evidence of CWD transmission to humans”
Subject: CWD aka MAD DEER/ELK TO HUMANS ???
Date: September 30, 2002 at 7:06 am PST
From: "Belay, Ermias"
To: Cc: "Race, Richard (NIH)" ; ; "Belay, Ermias"
Sent: Monday, September 30, 2002 9:22 AM
Subject: RE: TO CDC AND NIH - PUB MED- 3 MORE DEATHS - CWD - YOUNG HUNTERS
Dear Sir/Madam, In the Archives of Neurology you quoted (the abstract of which was attached to your email), we did not say CWD in humans will present like variant CJD.. That assumption would be wrong. I encourage you to read the whole article and call me if you have questions or need more clarification (phone: 404-639-3091).
Also, we do not claim that "no-one has ever been infected with prion disease from eating venison." Our conclusion stating that we found no strong evidence of CWD transmission to humans in the article you quoted or in any other forum is limited to the patients we investigated.
Ermias Belay, M.D. Centers for Disease Control and Prevention
Subject: TO CDC AND NIH - PUB MED- 3 MORE DEATHS - CWD - YOUNG HUNTERS
Sunday, November 10, 2002 6:26 PM .......snip........end..............TSS
-----Original Message-----
From:
Sent: Sunday, September 29, 2002 10:15 AM
To: rr26k@nih.gov; rrace@niaid.nih.gov; ebb8@CDC.GOV
Subject: TO CDC AND NIH - PUB MED- 3 MORE DEATHS - CWD - YOUNG HUNTERS
Sunday, November 10, 2002 6:26 PM .......snip........end..............TSS
Thursday, April 03, 2008
A prion disease of cervids: Chronic wasting disease 2008 1: Vet Res. 2008 Apr 3;39(4):41 A prion disease of cervids: Chronic wasting disease Sigurdson CJ.
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*** twenty-seven CJD patients who regularly consumed venison were reported to the Surveillance Center, however there have been no unusual or novel prion subtypes that might indicate the appearance of a new prion strain [7, 41].
snip... full text ;
https://www.vetres.org/articles/vetres/abs/2008/04/v08092/v08092.html
https://chronic-wasting-disease.blogspot.com/2008/04/prion-disease-of-cervids-chronic.html
Twenty-seven patients with CJD who regularly consumed elk and deer meat were reported to the National Prion Disease Pathology Surveillance Center at Case Western Reserve University, but none of these cases appeared to have a novel form of prion disease (Belay et al., 2001, 2003, 2004; P. Gambetti, unpublished observation); however, human disease acquired from CWD might have an unusual phenotype or a phenotype that is difficult to distinguish from that of sporadic CJD (sCJD). This uncertainty is a serious public health concern in the United States…
Colorado Surveillance Program for Chronic Wasting Disease Transmission to Humans Lessons From 2 Highly Suspicious but Negative Cases
C. Alan Anderson, MD; Patrick Bosque, MD; Christopher M. Filley, MD et al Author Affiliations Article Information Cite This Permissions Metrics
Arch Neurol Published Online: March 2007 2007;64;(3):439-441. doi:10.1001/archneur.64.3.439
related icon RELATED ARTICLES figure icon FIGURES
Abstract
Objective To describe 2 patients with rapidly progressive dementia and risk factors for exposure to chronic wasting disease (CWD) in whom extensive testing negated the possible transmission of CWD.
Design/Methods We describe the evaluation of 2 young adults with initial exposure histories and clinical presentations that suggested the possibility of CWD transmission to humans.
Patients A 52-year-old woman with possible laboratory exposure to CWD and a 25-year-old man who had consumed meat from a CWD endemic area.
Interventions Clinical evaluation, neuropathological examination, and genetic testing.
Results Neuropathological and genetic assessment in the 2 patients proved the diagnoses of early-onset Alzheimer disease and a rare genetic prion disease.
Conclusion No convincing cases of CWD transmission to humans have been detected in our surveillance program.
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Report of cases Case 1
A 52-year-old right-handed woman presented with a 1-year history of progressive memory loss, language impairment, visuospatial disturbance, and myoclonus. She related that she had been a histology technician in a laboratory that processed tissue specimens from deer and elk with CWD and had handled specimens without wearing gloves. Both she and her family expressed significant concerns about the possibility of transdermal transmission of CWD. Her family history was negative for dementia and other neurologic disorders. Brain magnetic resonance imaging showed mild diffuse volume loss, and electroencephalography demonstrated mild diffuse slowing. Other laboratory studies were unremarkable. Cerebrospinal fluid findings were unremarkable except for a weakly immunostaining 14-3-3 protein band, an indeterminate finding for the diagnosis of prion disease. Genetic testing of the prion protein gene was normal, revealing methionine homozygosity at codon 129. Brain biopsy results were negative for the presence of protease-resistant prion protein but showed definite Alzheimer disease with numerous neuritic plaques and tau-positive neurofibrillary tangles (Figure). Further analysis of brain tissue at the National Prion Disease Pathology Surveillance Center was negative for prion disease by Western blot analysis. Subsequent investigation by the state department of health revealed the patient had worked in an area of the laboratory that conducted necropsies on domestic animals and had never been assigned to the CWD testing laboratory. The Colorado Department of Public Health and Environment could not confirm that the technician had ever worked with deer and elk tissues.
Case 2 This 25-year-old right-handed man had a 4-month history of progressive gait disturbance, myoclonus, hallucinations, slowed cognition, impaired attention, and memory loss. He had hunted deer and elk in a CWD endemic area of southern Wyoming and cooked and ate the field-dressed meat. His family history was significant in that his mother had died of a dementing disease at age 40 years, although there was neither a clinical diagnosis nor an autopsy. Brain magnetic resonance imaging findings were unremarkable, and electroencephalography demonstrated 1-Hz high-amplitude periodic sharp wave complexes. Other laboratory studies had negative results. Testing for the 14-3-3 protein had positive results, but the cerebrospinal fluid was otherwise unremarkable. The diagnosis of Gerstmann-Sträussler-Scheinker syndrome, a familial prion disease, was confirmed with a detailed autopsy examination and referral of the brain to the National Prion Disease Pathology Surveillance Center. Autopsy brain tissue showed the presence of protease-resistant prion protein by Western blot analysis. Genetic evaluation revealed the P102L mutation in the prion protein gene with methionine/valine heterozygosity at codon 129.
Comment No cases of CWD transmission to humans have been detected to date. Colorado has implemented a multifaceted program to assess the human health risk, if any, of exposure to CWD. This includes making human prion disease a physician-reportable condition, conducting investigations and autopsies on all suspected prion disease cases, and initiating epidemiological studies on the incidence of human prion disease. Several cases with atypical features investigated as part of this project have been previously reported,4,10,11 including our second case in a review of prion disease in young patients.4 This patient was presented in an abstract by our group in 200310 and was then included in a review article published in 2004,4 prior to completion of our 5-year summary report; this case is presented here with updated information. Our group recently completed an epidemiological study that did not reveal any unusual patterns in neurological and neuropsychiatric mortality associated with areas of Colorado where CWD is endemic.12
In this report, we describe 2 patients in whom the possibility of human CWD transmission was considered high based on the clinical presentation and exposure history. Despite reported exposures to potentially CWD-positive tissues, alternate diagnoses were confirmed by clinical, neuropathological, and genetic evaluation. Both patients were found to have rare neurological diagnoses: early-onset Alzheimer disease in one and a familial form of prion disease, proven by identification of an established gene mutation, in the other. These cases underscore the importance of a thorough clinical, neuropathological, and genetic evaluation before a neurological or neuropsychiatric disorder in persons exposed to potentially infected game can be attributed to CWD. Although significant barriers can exist to obtaining autopsies on suspected Creutzfeldt-Jakob disease cases,13,14 postmortem brain examinations with referral to the National Prion Disease Pathology Surveillance Center are crucial to evaluating patients with prion disease.
Our experience over a 5-year period is consistent with previously described human case investigations4,15 and laboratory studies16-19 that also support the absence of human CWD to date. However, proving the absence of a rare transmission event to a person is exceedingly difficult. Still, while not conclusive, our results are reassuring from a clinical perspective. These cases support the need for a coordinated surveillance effort, including epidemiologic investigation, clinical evaluation, and neuropathological and genetic examination for all suspect cases. Further surveillance of the possibility of human transmission of CWD is warranted, particularly among persons with cervid exposure in endemic states.
Some news stories on a recent study finding a strong chronic wasting disease (CWD) species barrier between cervids such as deer and humans have concluded that there is no risk of a zoonotic spillover of the fatal prion disease.
But the study authors and other leading CWD and prion experts don't share that conviction.
"We think there's a low risk," senior study author Cathryn Haigh, PhD, Chief of the Prion Cell Biology Unit at the National Institutes of Health (NIH)'s Rocky Mountain Laboratories in Hamilton, Montana, told CIDRAP News. "We can't say no risk."
The research was published in Emerging Infectious Diseases in mid-May.
[The finding] is encouraging in that it emphasizes that at least with current CWD strains, there is a high species barrier, but it certainly doesn't mean that it [spillover] isn't possible or that the threshold of the species barrier might not change in the future when CWD strains evolve. Brian Appleby, MD
Brian Appleby, MD, director of the National Prion Disease Pathology Surveillance Center at Case Western Reserve University, said the study's conclusions are congruent with those from previous research but aren't the final answer to whether it can transmit to humans.
"They weren’t able to transmit chronic wasting disease to these human cerebral organoids, but that's not a human," he said. "And there are so many other factors that go into transmission outside of such experimental spaces. It is encouraging in that it emphasizes that at least with current CWD strains, there is a high species barrier, but it certainly doesn't mean that [spillover] isn't possible or that the threshold of the species barrier might not change in the future when CWD strains evolve."
Appleby is a cochair of a working group that is part of the CWD Contingency Planning Project at the University of Minnesota's Center for Infectious Disease Research and Policy (CIDRAP), publisher of CIDRAP News. CIDRAP has issued a statement saying that the study results haven't changed the urgent need for continued disease surveillance and preparation for a potential species jump.
Transmission of cervid prions to humanized mice demonstrates the zoonotic potential of CWD
Samia Hannaoui1 · Irina Zemlyankina1 · Sheng Chun Chang1 · Maria Immaculata Arifin1 · Vincent Béringue2 Debbie McKenzie3 · Hermann M. Schatzl1 · Sabine Gilch1 · Received: 24 May 2022 / Revised: 5 August 2022 / Accepted: 7 August 2022 / Published online: 22 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.
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Furthermore, our findings provide striking insights into how CWD might manifest in humans and the impact it may have on human health. We have used Wisc-1/CWD1, one of the most common CWD strains, notably white-tailed deer prions, which have been shown to be more prone to generate human prions in vitro [47]. This implies a high risk of exposure to this strain, e.g., through consumption or handling of infected carcasses, in contrast to rarer CWD strains, and therefore, an actual risk for human health. Fecal shedding of infectious prions, if it occurs in humans, is particularly concerning because of potential human-to-human transmission and adaptation of hCWD. Overall, our findings suggest that CWD surveil- lance in humans should encompass a wider spectrum of tissues/organs tested and include new criteria in the diag- nosis of potential patients. Supplementary Information The online version contains supplemen- tary material available at https:// doi. org/ 10. 1007/ s00401- 022- 02482-9.
Keywords Chronic wasting disease · CWD · Zoonotic potential · Prion strains · Zoonotic prions
Emerg Infect Dis Search in PMC Search in PubMed View in NLM Catalog Add to search . 2004 Jun;10(6):977–984. doi: 10.3201/eid1006.031082 Chronic Wasting Disease and Potential Transmission to Humans
Ermias D Belay *,✉, Ryan A Maddox *, Elizabeth S Williams †, Michael W Miller ‡, Pierluigi Gambetti §, Lawrence B Schonberger * Author information Copyright and License information PMCID: PMC3323184 PMID: 15207045
Abstract
Chronic wasting disease (CWD) of deer and elk is endemic in a tri-corner area of Colorado, Wyoming, and Nebraska, and new foci of CWD have been detected in other parts of the United States. Although detection in some areas may be related to increased surveillance, introduction of CWD due to translocation or natural migration of animals may account for some new foci of infection. Increasing spread of CWD has raised concerns about the potential for increasing human exposure to the CWD agent. The foodborne transmission of bovine spongiform encephalopathy to humans indicates that the species barrier may not completely protect humans from animal prion diseases. Conversion of human prion protein by CWD-associated prions has been demonstrated in an in vitro cell-free experiment, but limited investigations have not identified strong evidence for CWD transmission to humans. More epidemiologic and laboratory studies are needed to monitor the possibility of such transmissions.
Keywords: Chronic wasting disease, prion diseases, transmissible spongiform encephalopathy, interspecies transmission, prions
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However, epidemiologic and laboratory investigations of these case-patients indicated no strong evidence for a causal link between CWD and their CJD illness (33).
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Table 2. Creutzfeldt-Jakob disease patients investigated for a possible causal link of their illness with chronic wasting disease of deer and elk, United States
a. Case no. Age at death (y) Year of death Codon 129 Western blot Final diagnosis Eating of venison from
CWD-endemic area
1 25 2001 M/V Type 1 GSS 102 Yes
2 26 2001 M/M Type 2 CJD No
3b 28 2002 nd nd GSS 102 No
4 28 1997 M/M nd CJD No
5 28 2000 M/V Type 1 CJD No
6 30 1999 V/V Type 1 CJD No
7 54 2002 V/V Type 2 CJD No
8c 55 1999 M/M Type 1 CJD No
9d 61 2000 M/M Type 1 CJD Yes
10 63 2002 V/V Type 1 CJD No
11e 64 2002 M/M Type 1 CJD Yes
12 66 2001 M/M Type 1 CJD No Open in a new tab
see table 2
aCWD, chronic wasting disease; GSS, Gerstmann-Sträussler-Scheinker syndrome; CJD, Creutzfeldt-Jakob disease; nd, not done.
banalysis of postmortem brain tissue was consistent with GSS, and a GSS 102 mutation was confirmed in the family.
cInvestigated as part of a cluster of three case-patients who participated in "wild game feasts" in a cabin owned by one of the decedents.
dPatient grew up in an area known to be endemic for CWD and ate venison harvested locally; however, the CJD phenotype fits the most common form of sporadic CJD.
ePatient may have been successful in harvesting two deer since 1996 from a CWD-endemic area, but both deer tested negative for CWD.
In 2001, the case of a 25-year-old man who reportedly died of a prion disease after an illness lasting ≈22 months was investigated (Table 2). Although this man had hunted deer only rarely, his grandfather hunted deer and elk throughout much of the 1980s and 1990s and regularly shared the venison with the case-patient's family. The grandfather primarily hunted in southeastern Wyoming, around the known CWD-endemic area. The case-patient's illness began with a seizure and progressed to fatigue, poor concentration, and depression. Memory loss, ataxia, speech abnormalities, combative behavior, and recurrent seizures also developed. Histopathologic, immunohistochemical, and Western blot testing of brain autopsy samples confirmed a prion disease diagnosis. Analysis of the prion protein gene indicated a P102L mutation coupled with valine at the polymorphic codon 129 in the mutant allele, confirming a diagnosis of Gerstmann-Sträussler-Scheinker syndrome (GSS). This case-patient was unusually young even for a person with a GSS P102L mutation. It remains unknown whether the possible exposure of the case-patient to CWD-infected venison potentially contributed to the early onset of his prion disease.
In 2001, two additional CJD patients 26 and 28 years of age were reported from a single state (Table 2) (34). The patients grew up in adjacent counties and had illness onset within several months of each other. As a result of this fact and their unusually young age, a possible environmental source of infection, including exposure to CWD-infected venison, was considered. One of the patients died after an illness lasting 5–6 months that was characterized by progressive aphasia, memory loss, social withdrawal, vision disturbances, and seizure activity leading to status epilepticus and induced coma. Histopathologic, immunohistochemical, and Western blot testing of brain biopsy and autopsy samples confirmed a CJD diagnosis. The patient's disease phenotype corresponded to the MM2 sporadic CJD subtype reported by Parchi et al. (35). This patient did not hunt, and family members provided no history of regularly eating venison. The patient may have occasionally eaten venison originating from the Upper Peninsula of Michigan while away from home during his college years. However, ongoing surveillance has not detected CWD in Michigan deer (36).
The second patient died from an illness lasting <16 months. The patient's illness began with behavioral changes, including unusual outbursts of anger and depression. Confusion, memory loss, gait disturbances, incontinence, headaches, and photophobia also developed. Western blot analysis of frozen brain biopsy tissue confirmed a prion disease diagnosis. Immunohistochemical analysis of brain tissue obtained after the patient's death showed prion deposition consistent with GSS. A prion protein gene analysis could not be performed because appropriate samples were lacking. However, prion protein gene analysis of a blood sample from one of the patient's parents indicated a GSS P102L mutation. The patient did not hunt but may have eaten venison from Michigan once when he was 1–2 years old. The GSS diagnosis greatly reduced the likelihood that the two patients reported from adjacent counties had disease with a common origin.
Recently, rare neurologic disorders resulting in the deaths of three men who participated in "wild game feasts" in a cabin owned by one of the decedents created concern about the possible relationship of their illnesses with CWD (Table 2) (37). Two of the patients reportedly died of CJD, and the third died from Pick's disease. More than 50 persons were identified as possibly participating in these feasts; the three patients were the only participants reported to have died of a degenerative neurologic disorder. Reanalysis of autopsy brain tissues from the three patients at the National Prion Disease Pathology Surveillance Center indicated that two of them had no evidence of a prion disease by immunohistochemical analysis. CJD was confirmed in the third patient, who had clinicopathologic, codon 129, and prion characteristics similar to the most common sporadic CJD subtype (MM1/MV1) (35). This patient participated in the feasts only once, perhaps in the mid-1980s. In addition, the investigation found no evidence that the deer and elk meat served during the feasts originated from the known CWD-endemic areas of Colorado and Wyoming.
In 2003, CJD in two deer and elk hunters (54 and 66 years of age) was reported (38). The report implied that the patients had striking neuropathologic similarities and that their illness may represent a new entity in the spectrum of prion diseases. A third patient (63 years of age), who was also purported to have been a big game hunter, was subsequently reported from the same area. However, none of the three patients were reported to have eaten venison from the CWD-endemic areas of the western United States. The 66-year-old patient hunted most of his life in Washington State. Although information about the 54-year-old patient was limited, there was no evidence that he hunted in CWD-endemic areas. The third patient was not a hunter but ate venison harvested from Pennsylvania and Washington. The neuropathologic changes, Western blot profile, and genotype at codon 129 of the three patients each fit the MM1, VV1, or VV2 sporadic CJD subtype, indicating absence of phenotypic similarity among the cases or atypical neuropathologic features (35).
To date, only two nonfamilial CJD cases with a positive history of exposure to venison obtained from the known CWD-endemic areas have been reported. One of the patients was a 61-year-old woman who grew up in an area where this disease is known to be endemic, and she ate venison harvested locally. She died in 2000, and analysis of autopsy brain specimens confirmed that the patient's CJD phenotype fit the MM1 subtype, with no atypical neuropathologic features. The second patient was a 66-year-old man who was reported to have eaten venison from two deer harvested in a CWD-endemic area. Both deer tested negative for CWD, and the patient's illness was consistent with the MM1 CJD phenotype.
Despite the decades-long endemicity of CWD in Colorado and Wyoming, the incidence of CJD and the age distribution of CJD case-patients in these two states are similar to those seen in other parts of the United States. From 1979 to 2000, 67 CJD cases from Colorado and 7 from Wyoming were reported to the national multiple cause-of-death database. The average annual age-adjusted CJD death rate was 1.2 per million persons in Colorado and 0.8 in Wyoming. The proportion of CJD patients who died before age 55 in Colorado (13.4%) was similar to that of the national (10.2%). The only CJD case-patient <30 years of age in Colorado had iatrogenic CJD linked to receipt of human growth hormone injections. CJD was not reported in persons <55 years of age in Wyoming during the 22-year surveillance period.
Laboratory Studies
snip…
“However, epidemiologic and laboratory investigations of these case-patients indicated no strong evidence for a causal link between CWD and their CJD illness (33).” ???
“regular venison eating associated with a 9 FOLD INCREASE IN RISK OF CJD”
Subject: Re: DEER SPONGIFORM ENCEPHALOPATHY SURVEY & HOUND STUDY
Date: Fri, 18 Oct 2002 23:12:22 +0100
From: Steve Dealler Reply-To: Bovine Spongiform Encephalopathy Organization: Netscape Online member
To: BSE-L@ …
######## Bovine Spongiform Encephalopathy <BSE-L@UNI-KARLSRUHE.DE> #########
Dear Terry,
An excellent piece of review as this literature is desparately difficult to get back from Government sites. What happened with the deer was that an association between deer meat eating and sporadic CJD was found in about 1993. The evidence was not great but did not disappear after several years of asking CJD cases what they had eaten. I think that the work into deer disease largely stopped because it was not helpful to the UK industry...and no specific cases were reported.
Well, if you dont look adequately like they are in USA currenly then you wont find any!
Steve Dealler
########### http://mailhost.rz.uni-karlsruhe.de/warc/bse-l.html ############
Subject: DEER SPONGIFORM ENCEPHALOPATHY SURVEY & HOUND STUDY
From: "Terry S. Singeltary Sr." <flounder@WT.NET>
Reply To: Bovine Spongiform Encephalopathy <BSE-L@UNI-KARLSRUHE.DE>
Date: Thu, 17 Oct 2002 17:04:51 -0700
snip...
''The association between venison eating and risk of CJD shows similar pattern, with regular venison eating associated with a 9 FOLD INCREASE IN RISK OF CJD (p = 0.04).''
CREUTZFELDT JAKOB DISEASE SURVEILLANCE IN THE UNITED KINGDOM THIRD ANNUAL REPORT AUGUST 1994
snip...see full report ;
http://web.archive.org/web/20090506050043/http://www.bseinquiry.gov.uk/files/yb/1994/08/00004001.pdf
http://web.archive.org/web/20090506050007/http://www.bseinquiry.gov.uk/files/yb/1994/10/00003001.pdf
http://web.archive.org/web/20090506050244/http://www.bseinquiry.gov.uk/files/yb/1994/07/00001001.pdf
Stephen Dealler is a consultant medical microbiologist deal@airtime.co.uk BSE Inquiry Steve Dealler Management In Confidence BSE: Private Submission of Bovine Brain Dealler
snip...end
########### http://mailhost.rz.uni-karlsruhe.de/warc/bse-l.html ############
*** These results would seem to suggest that CWD does indeed have zoonotic potential, at least as judged by the compatibility of CWD prions and their human PrPC target. Furthermore, extrapolation from this simple in vitro assay suggests that if zoonotic CWD occurred, it would most likely effect those of the PRNP codon 129-MM genotype and that the PrPres type would be similar to that found in the most common subtype of sCJD (MM1).***
http://www.tandfonline.com/doi/full/10.4161/pri.28124?src=recsys
http://www.tandfonline.com/doi/pdf/10.4161/pri.28124?needAccess=true
https://wwwnc.cdc.gov/eid/article/20/1/13-0858_article
U.S. Army Prion Disease
HUMAN TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES: A CRITICAL SCIENTIFIC INVESTMENT
Final Report
National Prion Research Program
US Army Medical Research and Materiel Command Congressionally Directed Medical Research Programs
Fort Detrick, Maryland 2007
*** The potential impact of prion diseases on human health was greatly magnified by the recognition that interspecies transfer of BSE to humans by beef ingestion resulted in vCJD. While changes in animal feed constituents and slaughter practices appear to have curtailed vCJD, there is concern that CWD of free-ranging deer and elk in the U.S. might also cross the species barrier. Thus, consuming venison could be a source of human prion disease. Whether BSE and CWD represent interspecies scrapie transfer or are newly arisen prion diseases is unknown. Therefore, the possibility of transmission of prion disease through other food animals cannot be ruled out. There is evidence that vCJD can be transmitted through blood transfusion. There is likely a pool of unknown size of asymptomatic individuals infected with vCJD, and there may be asymptomatic individuals infected with the CWD equivalent. These circumstances represent a potential threat to blood, blood products, and plasma supplies.
http://cdmrp.army.mil/prevfunded/nprp/NPRP_Summit_Final_Report.pdf
archived url;
https://web.archive.org/web/20120928015709/http://cdmrp.army.mil/prevfunded/nprp/NPRP_Summit_Final_Report.pdf
Limited transmission of cervid prions to nonhuman primates provides insights into the zoonotic potential of chronic wasting disease
SAMIA HANNAOUI, SANDRA PRITZKOW, WIEBKE M. JÜRGENS-WEMHEUER, DIRK MOTZKUS, [...] , AND HERMANN M. SCHÄTZL +12 authors Authors Info & Affiliations
SCIENCE ADVANCES
27 May 2026 Vol 12, Issue 22 DOI: 10.1126/sciadv.aeb7613
Abstract
Chronic wasting disease (CWD) is an expanding prion disease of cervids. CWD prions persist in the environment, are shed in excreta, and accumulate in tissues of infected cervids, raising concerns about its zoonotic potential. Using cynomolgus macaques, we explored the zoonotic potential of CWD. Although most inoculated macaques remained asymptomatic, sensitive in vitro prion amplification assays revealed low levels of prions in macaque tissues. Inoculation of transgenic mice and bank voles with macaque tissues induced prion disease, achieving 100% transmission rates upon serial passage. One interpretation of these findings is that CWD prions retain infectivity across species and that primate infection may manifest atypically while still enabling transmission. Our results challenge earlier conclusions that minimize the zoonotic risk of CWD and underscore the need for continued surveillance.
snip…
These findings suggest that cynomolgus macaques, often considered the most relevant model for assessing prion zoonotic potential, can support CWD infection under experimental conditions, although disease manifestation is atypical and only became evident through transmission to highly susceptible rodent models with unusual tissue tropism. While these results do not demonstrate efficient transmission of CWD to macaques, they indicate that this cross-species transmission cannot be excluded and warrants continued attention. These observations provide critical insights into how prion disease might present in the event of a spillover, reinforcing the need for sustained vigilance and further research into prion adaptation and zoonotic potential.
snip…
Together, these results underscore the potential zoonotic threat that may manifest subtly in primates while maintaining infectivity and transmissibility, opening the potential to adapt to humans. These findings prompt critical questions about the broader zoonotic landscape of CWD and emphasize the need for vigilant monitoring as CWD continues to spread through diverse ecosystems, broadening the potential for human exposure.
snip…
In summary, macaques infected orally (AU501 and AU467), intracerebrally (AU408 and AU469), or by intracerebrally steel wire implantation (AU519 and AU389) exhibited no detectable PrPSc signals on immunoblots and minimal prion detection via immunohistochemistry (IHC); however, prion seeding activity in brains and spleens of some animals were confirmed using highly sensitive prion conversion assays.
snip…
Our group (25) and others highlighted the importance of sensitive prion detection methods on interspecies prion transmission, where RT-QuIC and PMCA proved more reliable in detecting and identifying subclinical prion infections than traditional techniques, e.g., IHC and immunoblot that showed a higher detection threshold than the amplification assays. These findings suggest that standard diagnostic tools may underestimate prion infectivity in early or subclinical stages, raising concerns about undetected transmission risks. In addition, it is worth mentioning that while several prion-positive materials were passaged into bank voles, not all successfully adapted, reinforcing the specificity of the observed results. The selective propagation of certain materials indicates a requirement for specific strain compatibility or adaptation to the bank vole model. The persistence of prion seeding activity in both symptomatic and asymptomatic animals further suggests that subclinical infections may pose a long-term zoonotic risk, especially with repeated or prolonged exposure to CWD prions, including new CWD strains with different potential to cross the species barrier to humans (18, 21, 23, 73). Previous research has established the presence of distinct CWD prion types that result in different CWD strains in a new host (41, 74, 75), which could further complicate efforts to assess human model susceptibility to CWD. CWD prions have potential for strain adaptation/evolution in different hosts with relative resistance, suggesting that certain CWD isolates may pose a risk of crossing into new species, including intermediate hosts (76–79). Together, these observations highlight a scenario in which CWD transmission to primates may be inefficient, clinically atypical, and largely subclinical yet biologically capable of generating infectious prions with zoonotic relevance.
Previous reports demonstrated that prions can silently replicate in hosts, often going undetected by traditional diagnostic tools, while still being capable of transmission and eventual disease progression (80–82). In a previous study assessing the zoonotic potential of CWD using a transgenic humanized mouse model (25), we reported the involvement of gastrointestinal tissues, but we did not evaluate the transmissibility of these prions. In the present study, we demonstrated the infectivity and transmissibility of prions in gastrointestinal tissues in bank voles, where inoculation with small intestine homogenate, positive only in RT-QuIC for prion seeding activity, led to a 100% attack rate. The presence of subclinical prion carriers underscores the need for advanced diagnostic techniques to better understand prion infection’s dormant phase and to identify potential reservoirs currently overlooked in prion human diagnostics. This approach is essential to prevent transmission from asymptomatic carriers or those with atypical clinical symptoms. As the geographic range and prevalence of CWD-infected animals continue to expand, the risk of exposure to humans may escalate. As with any pathogen, an increase in CWD prevalence and prion replication provides more opportunities for adaptations, mutations, and potential zoonotic transmission; hence, our results and the growing concern for this question (83) warrant serious consideration.
We stress that our results do not imply efficient transmission to primates; rather, they reveal that exposure under certain conditions can lead to sustained prion infectivity that remains undetectable by classical diagnostic tools.
https://www.science.org/doi/10.1126/sciadv.aeb7613
“ Highly endemic states had a higher rate of prion disease mortality compared to non-CWD states”
Prion Conference 2018
P190 Human prion disease mortality rates by occurrence of chronic wasting disease in free ranging cervids, United States
Abrams JY (1), Maddox RA (1), Schonberger LB (1), Person MK (1), Appleby BS (2), Belay ED (1)
(1) Centers for Disease Control and Prevention (CDC), National Center for Emerging and Zoonotic Infectious Diseases, Atlanta, GA, USA (2) Case Western Reserve University, National Prion Disease Pathology Surveillance Center (NPDPSC), Cleveland, OH, USA.
Background
Chronic wasting disease (CWD) is a prion disease of deer and elk that has been identified in free ranging cervids in 23 US states. While there is currently no epidemiological evidence for zoonotic transmission through the consumption of contaminated venison, studies suggest the CWD agent can cross the species barrier in experimental models designed to closely mimic humans. We compared rates of human prion disease in states with and without CWD to examine the possibility of undetermined zoonotic transmission.
Methods
Death records from the National Center for Health Statistics, case records from the National Prion Disease Pathology Surveillance Center, and additional state case reports were combined to create a database of human prion disease cases from 2003-2015. Identification of CWD in each state was determined through reports of positive CWD tests by state wildlife agencies. Age- and race-adjusted mortality rates for human prion disease, excluding cases with known etiology, were determined for four categories of states based on CWD occurrence: highly endemic (>16 counties with CWD identified in free-ranging cervids); moderately endemic (3-10 counties with CWD); low endemic (1-2 counties with CWD); and no CWD states. States were counted as having no CWD until the year CWD was first identified. Analyses stratified by age, sex, and time period were also conducted to focus on subgroups for which zoonotic transmission would be more likely to be detected: cases <55 years old, male sex, and the latter half of the study (2010-2015).
Results
Highly endemic states had a higher rate of prion disease mortality compared to non-CWD states (rate ratio [RR]: 1.12, 95% confidence interval [CI] = 1.01 - 1.23), as did low endemic states (RR: 1.15, 95% CI = 1.04 - 1.27). Moderately endemic states did not have an elevated mortality rate (RR: 1.05, 95% CI = 0.93 - 1.17). In age-stratified analyses, prion disease mortality rates among the <55 year old population were elevated for moderately endemic states (RR: 1.57, 95% CI = 1.10 – 2.24) while mortality rates were elevated among those ≥55 for highly endemic states (RR: 1.13, 95% CI = 1.02 - 1.26) and low endemic states (RR: 1.16, 95% CI = 1.04 - 1.29). In other stratified analyses, prion disease mortality rates for males were only elevated for low endemic states (RR: 1.27, 95% CI = 1.10 - 1.48), and none of the categories of CWD-endemic states had elevated mortality rates for the latter time period (2010-2015).
Conclusions
While higher prion disease mortality rates in certain categories of states with CWD in free-ranging cervids were noted, additional stratified analyses did not reveal markedly elevated rates for potentially sensitive subgroups that would be suggestive of zoonotic transmission. Unknown confounding factors or other biases may explain state-by-state differences in prion disease mortality.
“ Highly endemic states had a higher rate of prion disease mortality compared to non-CWD states”
=====
P172 Peripheral Neuropathy in Patients with Prion Disease
Wang H(1), Cohen M(1), Appleby BS(1,2)
(1) University Hospitals Cleveland Medical Center, Cleveland, Ohio (2) National Prion Disease Pathology Surveillance Center, Cleveland, Ohio.
Prion disease is a fatal progressive neurodegenerative disease due to deposition of an abnormal protease-resistant isoform of prion protein. Typical symptoms include rapidly progressive dementia, myoclonus, visual disturbance and hallucinations. Interestingly, in patients with prion disease, the abnormal protein canould also be found in the peripheral nervous system. Case reports of prion deposition in peripheral nerves have been reported. Peripheral nerve involvement is thought to be uncommon; however, little is known about the exact prevalence and features of peripheral neuropathy in patients with prion disease.
We reviewed autopsy-proven prion cases from the National Prion Disease Pathology Surveillance Center that were diagnosed between September 2016 to March 2017. We collected information regarding prion protein diagnosis, demographics, comorbidities, clinical symptoms, physical exam, neuropathology, molecular subtype, genetics lab, brain MRI, image and EMG reports. Our study included 104 patients. Thirteen (12.5%) patients had either subjective symptoms or objective signs of peripheral neuropathy. Among these 13 patients, 3 had other known potential etiologies of peripheral neuropathy such as vitamin B12 deficiency or prior chemotherapy. Among 10 patients that had no other clear etiology, 3 (30%) had familial CJD. The most common sCJD subtype was MV1-2 (30%), followed by MM1-2 (20%). The Majority of cases wasere male (60%). Half of them had exposure to wild game. The most common subjective symptoms were tingling and/or numbness of distal extremities. The most common objective finding was diminished vibratory sensation in the feet. Half of them had an EMG with the findings ranging from fasciculations to axonal polyneuropathy or demyelinating polyneuropathy.
Our study provides an overview of the pattern of peripheral neuropathy in patients with prion disease. Among patients with peripheral neuropathy symptoms or signs, majority has polyneuropathy. It is important to document the baseline frequency of peripheral neuropathy in prion diseases as these symptoms may become important when conducting surveillance for potential novel zoonotic prion diseases.
“The most common sCJD subtype was MV1-2 (30%), followed by MM1-2 (20%). The Majority of cases wasere male (60%). Half of them had exposure to wild game.”
=====
WA2 Oral transmission of CWD into Cynomolgus macaques: signs of atypical disease, prion conversion and infectivity in macaques and bio-assayed transgenic mice
Schatzl HM (1, 2), Hannaoui S (1, 2), Cheng Y-C (1, 2), Gilch S (1, 2), Beekes M (3), SchulzSchaeffer W (4), Stahl-Hennig C (5) and Czub S (2, 6)
(1) University of Calgary, Calgary Prion Research Unit, Calgary, Canada (2) University of Calgary, Faculty of Veterinary Medicine, Calgary, Canada, (3) Robert Koch Institute, Berlin, Germany, (4) University of Homburg/Saar, Homburg, Germany, (5) German Primate Center, Goettingen, Germany, (6) Canadian Food Inspection Agency (CFIA), Lethbridge, Canada.
To date, BSE is the only example of interspecies transmission of an animal prion disease into humans. The potential zoonotic transmission of CWD is an alarming issue and was addressed by many groups using a variety of in vitro and in vivo experimental systems. Evidence from these studies indicated a substantial, if not absolute, species barrier, aligning with the absence of epidemiological evidence suggesting transmission into humans. Studies in non-human primates were not conclusive so far, with oral transmission into new-world monkeys and no transmission into old-world monkeys. Our consortium has challenged 18 Cynomolgus macaques with characterized CWD material, focusing on oral transmission with muscle tissue. Some macaques have orally received a total of 5 kg of muscle material over a period of 2 years. After 5-7 years of incubation time some animals showed clinical symptoms indicative of prion disease, and prion neuropathology and PrPSc deposition were found in spinal cord and brain of euthanized animals. PrPSc in immunoblot was weakly detected in some spinal cord materials and various tissues tested positive in RT-QuIC, including lymph node and spleen homogenates. To prove prion infectivity in the macaque tissues, we have intracerebrally inoculated 2 lines of transgenic mice, expressing either elk or human PrP. At least 3 TgElk mice, receiving tissues from 2 different macaques, showed clinical signs of a progressive prion disease and brains were positive in immunoblot and RT-QuIC. Tissues (brain, spinal cord and spleen) from these and preclinical mice are currently tested using various read-outs and by second passage in mice. Transgenic mice expressing human PrP were so far negative for clear clinical prion disease (some mice >300 days p.i.). In parallel, the same macaque materials are inoculated into bank voles.
Taken together, there is strong evidence of transmissibility of CWD orally into macaques and from macaque tissues into transgenic mouse models, although with an incomplete attack rate. The clinical and pathological presentation in macaques was mostly atypical, with a strong emphasis on spinal cord pathology. Our ongoing studies will show whether the transmission of CWD into macaques and passage in transgenic mice represents a form of non-adaptive prion amplification, and whether macaque-adapted prions have the potential to infect mice expressing human PrP.
The notion that CWD can be transmitted orally into both new-world and old-world non-human primates asks for a careful reevaluation of the zoonotic risk of CWD.
See also poster P103
***> The notion that CWD can be transmitted orally into both new-world and old-world non-human primates asks for a careful reevaluation of the zoonotic risk of CWD.
====
Source Prion Conference 2018 Abstracts
https://hal.science/hal-04236401v1/file/Prion%202018%20book%20of%20abstracts%20180516.pdf
http://transmissiblespongiformencephalopathy.blogspot.com/2018/05/prion-2018-may-22-25-2018-santiago-de.html
http://chronic-wasting-disease.blogspot.com/2018/07/oral-transmission-of-cwd-into.html
http://prionconference.blogspot.com/2018/
So, this is what we leave our children and grandchildren?
***> CWD TSE Prion Zoonotic Zoonosis Humans, What if? <***
CDC CWD TSE Prion Update 2024
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
see archived url link;
https://web.archive.org/web/20240617224730/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
================================
Our results suggest that CWD might infect humans, although the transmission barrier is likely higher compared to zoonotic transmission of cattle prions. Notably, our data suggest a different clinical presentation, prion signature, and tissue tropism, which causes challenges for detection by current diagnostic assays. Furthermore, the presence of infectious prions in feces is concerning because if this occurs in humans, it is a source for human-to-human transmission. These findings have strong implications for public health and CWD management.
In this study, we evaluated the zoonotic potential of CWD using a transgenic mouse model overexpressing human M129-PrPC (tg650 [12]). We inoculated tg650mice intracerebrally with two deer CWD isolates, Wisc-1 and 116AG [22, 23, 27, 29]. We demonstrate that this transgenic line was susceptible to infection with CWD prions and displayed a distinct leading clinical sign, an atypical PrPSc signature and unusual fecal shedding of infectious prions. Importantly, these prions generated by the human PrP transgenic mice were transmissible upon passage. Our results are the first evidence of a zoonotic risk of CWD when using one of the most common CWD strains, Wisc-1/CWD1 for infection. We demonstrated in a human transgenic mouse model that the species barrier for transmission of CWD to humans is not absolute. The fact that its signature was not typical raises the questions whether CWD would manifest in humans as a subclinical infection, whether it would arise through direct or indirect transmission including an intermediate host, or a silent to uncovered human-to-human transmission, and whether current detection techniques will be suffcient to unveil its presence.
Our findings strongly suggest that CWD should be regarded as an actual public health risk. Here, we use humanized mice to show that CWD prions can cross the species barrier to humans, and remarkably, infectious prions can be excreted in feces.
Our results indicate that if CWD crosses the species-barrier to humans, it is unlikely to resemble the most common forms of human prion diseases with respect to clinical signs, tissue tropism and PrPSc signature. For instance, PrPSc in variable protease-sensitive prionopathy (VPSPr), a sporadic form of human prion disease, and in the genetic form Gerstmann-Sträussler-Scheinker syndrome (GSS) is defined by an atypical PK-resistant PrPSc fragment that is non-glycosylated and truncated at both C- and N-termini, with a molecular weight between 6 and 8 kDa [24, 44–46]. These biochemical features are unique and distinctive from PrPSc (PrP27-30) found in most other human or animal prion disease. The atypical PrPSc signature detected in brain homogenate of tg650 mice #321 (1st passage) and #3063 (2nd passage), and the 7–8 kDa fragment (Figs. 2, 4) are very similar to that of GSS, both in terms of migration profile and the N-terminal cleavage site.
CWD in humans might remain subclinical but with PrPSc deposits in the brain with an unusual morphology that does not resemble the patterns usually seen in different prion diseases (e.g., mouse #328; Fig. 3), clinical with untraceable abnormal PrP (e.g., mouse #327) but still transmissible and uncovered upon subsequent passage (e.g., mouse #3063; Fig. 4), or prions have other reservoirs than the usual ones, hence the presence of infectivity in feces (e.g., mouse #327) suggesting a potential for human-to-human transmission and a real iatrogenic risk that might be unrecognizable.
“suggesting a potential for human-to-human transmission and a real iatrogenic risk that might be unrecognizable.”
=================================
Supplementary Information The online version contains supplementary material available at
https://doi.org/10.1007/s00401-022-02482-9
snip...see full text;
https://link.springer.com/article/10.1007/s00401-022-02482-9
https://link.springer.com/content/pdf/10.1007/s00401-022-02482-9.pdf
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
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
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
18. Zoonotic potential of moose-derived chronic wasting disease prions after adaptation in intermediate species
“ After adaptation in this host, moose CWD prions were able to transmit in mice expressing either bovine or human PrPC with high efficacy.”
https://pmc.ncbi.nlm.nih.gov/articles/PMC11610568/
Abrams JY (1), Maddox RA (1), Schonberger LB (1), Person MK (1), Appleby BS (2), Belay ED (1)
(1) Centers for Disease Control and Prevention (CDC), National Center for Emerging and Zoonotic Infectious Diseases, Atlanta, GA, USA (2) Case Western Reserve University, National Prion Disease Pathology Surveillance Center (NPDPSC), Cleveland, OH, USA.
Background
Chronic wasting disease (CWD) is a prion disease of deer and elk that has been identified in free ranging cervids in 23 US states. While there is currently no epidemiological evidence for zoonotic transmission through the consumption of contaminated venison, studies suggest the CWD agent can cross the species barrier in experimental models designed to closely mimic humans. We compared rates of human prion disease in states with and without CWD to examine the possibility of undetermined zoonotic transmission.
Methods
Death records from the National Center for Health Statistics, case records from the National Prion Disease Pathology Surveillance Center, and additional state case reports were combined to create a database of human prion disease cases from 2003-2015. Identification of CWD in each state was determined through reports of positive CWD tests by state wildlife agencies. Age- and race-adjusted mortality rates for human prion disease, excluding cases with known etiology, were determined for four categories of states based on CWD occurrence: highly endemic (>16 counties with CWD identified in free-ranging cervids); moderately endemic (3-10 counties with CWD); low endemic (1-2 counties with CWD); and no CWD states. States were counted as having no CWD until the year CWD was first identified. Analyses stratified by age, sex, and time period were also conducted to focus on subgroups for which zoonotic transmission would be more likely to be detected: cases <55 years old, male sex, and the latter half of the study (2010-2015).
Results
Highly endemic states had a higher rate of prion disease mortality compared to non-CWD states (rate ratio [RR]: 1.12, 95% confidence interval [CI] = 1.01 - 1.23), as did low endemic states (RR: 1.15, 95% CI = 1.04 - 1.27). Moderately endemic states did not have an elevated mortality rate (RR: 1.05, 95% CI = 0.93 - 1.17). In age-stratified analyses, prion disease mortality rates among the <55 year old population were elevated for moderately endemic states (RR: 1.57, 95% CI = 1.10 – 2.24) while mortality rates were elevated among those ≥55 for highly endemic states (RR: 1.13, 95% CI = 1.02 - 1.26) and low endemic states (RR: 1.16, 95% CI = 1.04 - 1.29). In other stratified analyses, prion disease mortality rates for males were only elevated for low endemic states (RR: 1.27, 95% CI = 1.10 - 1.48), and none of the categories of CWD-endemic states had elevated mortality rates for the latter time period (2010-2015).
Conclusions
While higher prion disease mortality rates in certain categories of states with CWD in free-ranging cervids were noted, additional stratified analyses did not reveal markedly elevated rates for potentially sensitive subgroups that would be suggestive of zoonotic transmission. Unknown confounding factors or other biases may explain state-by-state differences in prion disease mortality.
“ Highly endemic states had a higher rate of prion disease mortality compared to non-CWD states”
=====
P172 Peripheral Neuropathy in Patients with Prion Disease
Wang H(1), Cohen M(1), Appleby BS(1,2)
(1) University Hospitals Cleveland Medical Center, Cleveland, Ohio (2) National Prion Disease Pathology Surveillance Center, Cleveland, Ohio.
Prion disease is a fatal progressive neurodegenerative disease due to deposition of an abnormal protease-resistant isoform of prion protein. Typical symptoms include rapidly progressive dementia, myoclonus, visual disturbance and hallucinations. Interestingly, in patients with prion disease, the abnormal protein canould also be found in the peripheral nervous system. Case reports of prion deposition in peripheral nerves have been reported. Peripheral nerve involvement is thought to be uncommon; however, little is known about the exact prevalence and features of peripheral neuropathy in patients with prion disease.
We reviewed autopsy-proven prion cases from the National Prion Disease Pathology Surveillance Center that were diagnosed between September 2016 to March 2017. We collected information regarding prion protein diagnosis, demographics, comorbidities, clinical symptoms, physical exam, neuropathology, molecular subtype, genetics lab, brain MRI, image and EMG reports. Our study included 104 patients. Thirteen (12.5%) patients had either subjective symptoms or objective signs of peripheral neuropathy. Among these 13 patients, 3 had other known potential etiologies of peripheral neuropathy such as vitamin B12 deficiency or prior chemotherapy. Among 10 patients that had no other clear etiology, 3 (30%) had familial CJD. The most common sCJD subtype was MV1-2 (30%), followed by MM1-2 (20%). The Majority of cases wasere male (60%). Half of them had exposure to wild game. The most common subjective symptoms were tingling and/or numbness of distal extremities. The most common objective finding was diminished vibratory sensation in the feet. Half of them had an EMG with the findings ranging from fasciculations to axonal polyneuropathy or demyelinating polyneuropathy.
Our study provides an overview of the pattern of peripheral neuropathy in patients with prion disease. Among patients with peripheral neuropathy symptoms or signs, majority has polyneuropathy. It is important to document the baseline frequency of peripheral neuropathy in prion diseases as these symptoms may become important when conducting surveillance for potential novel zoonotic prion diseases.
“The most common sCJD subtype was MV1-2 (30%), followed by MM1-2 (20%). The Majority of cases wasere male (60%). Half of them had exposure to wild game.”
=====
WA2 Oral transmission of CWD into Cynomolgus macaques: signs of atypical disease, prion conversion and infectivity in macaques and bio-assayed transgenic mice
Schatzl HM (1, 2), Hannaoui S (1, 2), Cheng Y-C (1, 2), Gilch S (1, 2), Beekes M (3), SchulzSchaeffer W (4), Stahl-Hennig C (5) and Czub S (2, 6)
(1) University of Calgary, Calgary Prion Research Unit, Calgary, Canada (2) University of Calgary, Faculty of Veterinary Medicine, Calgary, Canada, (3) Robert Koch Institute, Berlin, Germany, (4) University of Homburg/Saar, Homburg, Germany, (5) German Primate Center, Goettingen, Germany, (6) Canadian Food Inspection Agency (CFIA), Lethbridge, Canada.
To date, BSE is the only example of interspecies transmission of an animal prion disease into humans. The potential zoonotic transmission of CWD is an alarming issue and was addressed by many groups using a variety of in vitro and in vivo experimental systems. Evidence from these studies indicated a substantial, if not absolute, species barrier, aligning with the absence of epidemiological evidence suggesting transmission into humans. Studies in non-human primates were not conclusive so far, with oral transmission into new-world monkeys and no transmission into old-world monkeys. Our consortium has challenged 18 Cynomolgus macaques with characterized CWD material, focusing on oral transmission with muscle tissue. Some macaques have orally received a total of 5 kg of muscle material over a period of 2 years. After 5-7 years of incubation time some animals showed clinical symptoms indicative of prion disease, and prion neuropathology and PrPSc deposition were found in spinal cord and brain of euthanized animals. PrPSc in immunoblot was weakly detected in some spinal cord materials and various tissues tested positive in RT-QuIC, including lymph node and spleen homogenates. To prove prion infectivity in the macaque tissues, we have intracerebrally inoculated 2 lines of transgenic mice, expressing either elk or human PrP. At least 3 TgElk mice, receiving tissues from 2 different macaques, showed clinical signs of a progressive prion disease and brains were positive in immunoblot and RT-QuIC. Tissues (brain, spinal cord and spleen) from these and preclinical mice are currently tested using various read-outs and by second passage in mice. Transgenic mice expressing human PrP were so far negative for clear clinical prion disease (some mice >300 days p.i.). In parallel, the same macaque materials are inoculated into bank voles.
Taken together, there is strong evidence of transmissibility of CWD orally into macaques and from macaque tissues into transgenic mouse models, although with an incomplete attack rate. The clinical and pathological presentation in macaques was mostly atypical, with a strong emphasis on spinal cord pathology. Our ongoing studies will show whether the transmission of CWD into macaques and passage in transgenic mice represents a form of non-adaptive prion amplification, and whether macaque-adapted prions have the potential to infect mice expressing human PrP.
The notion that CWD can be transmitted orally into both new-world and old-world non-human primates asks for a careful reevaluation of the zoonotic risk of CWD.
See also poster P103
***> The notion that CWD can be transmitted orally into both new-world and old-world non-human primates asks for a careful reevaluation of the zoonotic risk of CWD.
====
Source Prion Conference 2018 Abstracts
https://hal.science/hal-04236401v1/file/Prion%202018%20book%20of%20abstracts%20180516.pdf
http://transmissiblespongiformencephalopathy.blogspot.com/2018/05/prion-2018-may-22-25-2018-santiago-de.html
http://chronic-wasting-disease.blogspot.com/2018/07/oral-transmission-of-cwd-into.html
http://prionconference.blogspot.com/2018/
So, this is what we leave our children and grandchildren?
***> CWD TSE Prion Zoonotic Zoonosis Humans, What if? <***
CDC CWD TSE Prion Update 2024
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
see archived url link;
https://web.archive.org/web/20240617224730/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
================================
Our results suggest that CWD might infect humans, although the transmission barrier is likely higher compared to zoonotic transmission of cattle prions. Notably, our data suggest a different clinical presentation, prion signature, and tissue tropism, which causes challenges for detection by current diagnostic assays. Furthermore, the presence of infectious prions in feces is concerning because if this occurs in humans, it is a source for human-to-human transmission. These findings have strong implications for public health and CWD management.
In this study, we evaluated the zoonotic potential of CWD using a transgenic mouse model overexpressing human M129-PrPC (tg650 [12]). We inoculated tg650mice intracerebrally with two deer CWD isolates, Wisc-1 and 116AG [22, 23, 27, 29]. We demonstrate that this transgenic line was susceptible to infection with CWD prions and displayed a distinct leading clinical sign, an atypical PrPSc signature and unusual fecal shedding of infectious prions. Importantly, these prions generated by the human PrP transgenic mice were transmissible upon passage. Our results are the first evidence of a zoonotic risk of CWD when using one of the most common CWD strains, Wisc-1/CWD1 for infection. We demonstrated in a human transgenic mouse model that the species barrier for transmission of CWD to humans is not absolute. The fact that its signature was not typical raises the questions whether CWD would manifest in humans as a subclinical infection, whether it would arise through direct or indirect transmission including an intermediate host, or a silent to uncovered human-to-human transmission, and whether current detection techniques will be suffcient to unveil its presence.
Our findings strongly suggest that CWD should be regarded as an actual public health risk. Here, we use humanized mice to show that CWD prions can cross the species barrier to humans, and remarkably, infectious prions can be excreted in feces.
Our results indicate that if CWD crosses the species-barrier to humans, it is unlikely to resemble the most common forms of human prion diseases with respect to clinical signs, tissue tropism and PrPSc signature. For instance, PrPSc in variable protease-sensitive prionopathy (VPSPr), a sporadic form of human prion disease, and in the genetic form Gerstmann-Sträussler-Scheinker syndrome (GSS) is defined by an atypical PK-resistant PrPSc fragment that is non-glycosylated and truncated at both C- and N-termini, with a molecular weight between 6 and 8 kDa [24, 44–46]. These biochemical features are unique and distinctive from PrPSc (PrP27-30) found in most other human or animal prion disease. The atypical PrPSc signature detected in brain homogenate of tg650 mice #321 (1st passage) and #3063 (2nd passage), and the 7–8 kDa fragment (Figs. 2, 4) are very similar to that of GSS, both in terms of migration profile and the N-terminal cleavage site.
CWD in humans might remain subclinical but with PrPSc deposits in the brain with an unusual morphology that does not resemble the patterns usually seen in different prion diseases (e.g., mouse #328; Fig. 3), clinical with untraceable abnormal PrP (e.g., mouse #327) but still transmissible and uncovered upon subsequent passage (e.g., mouse #3063; Fig. 4), or prions have other reservoirs than the usual ones, hence the presence of infectivity in feces (e.g., mouse #327) suggesting a potential for human-to-human transmission and a real iatrogenic risk that might be unrecognizable.
“suggesting a potential for human-to-human transmission and a real iatrogenic risk that might be unrecognizable.”
=================================
Supplementary Information The online version contains supplementary material available at
https://doi.org/10.1007/s00401-022-02482-9
snip...see full text;
https://link.springer.com/article/10.1007/s00401-022-02482-9
https://link.springer.com/content/pdf/10.1007/s00401-022-02482-9.pdf
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
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
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
18. Zoonotic potential of moose-derived chronic wasting disease prions after adaptation in intermediate species
“ After adaptation in this host, moose CWD prions were able to transmit in mice expressing either bovine or human PrPC with high efficacy.”
https://pmc.ncbi.nlm.nih.gov/articles/PMC11610568/
Tuesday, June 9, 2026
Hazard identification for the risks to terrestrial animal health from the import of hay and straw, BSE, CWD, Scrapie, TSE, Prion
USA Report, Scrapie, CWD, BSE, TSE, Cattle, Sheep, Pigs, Cervid, Humans, Zoonotic, 2026
April 2026
WEDNESDAY, MAY 27, 2026
Limited transmission of cervid prions to nonhuman primates provides insights into the zoonotic potential of chronic wasting disease
US NATIONAL PRION DISEASE PATHOLOGY SURVEILLANCE CENTER CJD TSE REPORT SEPTEMBER 2025
From the first full year of reporting CJD TSE in the US in 2000, where 90 cases of CJD was reported that year, to today, where in September 2025, the number of CJD cases reported in the last full year reporting, which would have been 2024, the number of CJD cases for 2024 was 249 cases. So, from the first full year 2000 CJD cases were 90 cases confirmed in that year, to 2024, where 2024 CJD statistics rose to 249 confirmed CJD cases in a single year. A dramatic increase in deaths, from figures that don’t seem to be dramatic. But thes figures today, they are not from “better surveillance”, that dog don’t hunt no more. They have been saying this for over 25 years, year after year, well it’s time to call it for what it is, Human Transmissible Spongiform Encephalopathy TSE Prion cases are rising, and it’s NOT because of better surveillance, or just a “happenstance of bad luck, that 85%+ of all human cases, sporadic CJD, including VPSPr, just happen spontaneously, no, it’s because of unknown environmental factors, and or iatrogenic factors, imho…terry
US NATIONAL PRION DISEASE PATHOLOGY SURVEILLANCE CENTER CJD TSE REPORT SEPTEMBER 2025
https://prionunitusaupdate.blogspot.com/2025/10/us-national-prion-disease-pathology.html
So, this is what we leave our children and grandchildren?
2001 Singeltary on CJD, Journal of American Medical Association
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
RE-Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob disease in the United States 2003 Singeltary Journal of Neurology
26 MARCH 2003
RE-Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob disease in the United States
Terry S. Singeltary, retired (medically)
I lost my mother to hvCJD (Heidenhain Variant CJD). I would like to comment on the CDC's attempts to monitor the occurrence of emerging forms of CJD. Asante, Collinge et al [1] have reported that BSE transmission to the 129-methionine genotype can lead to an alternate phenotype that is indistinguishable from type 2 PrPSc, the commonest sporadic CJD. However, CJD and all human TSEs are not reportable nationally. CJD and all human TSEs must be made reportable in every state and internationally. I hope that the CDC does not continue to expect us to still believe that the 85%+ of all CJD cases which are sporadic are all spontaneous, without route/source. We have many TSEs in the USA in both animal and man. CWD in deer/elk is spreading rapidly and CWD does transmit to mink, ferret, cattle, and squirrel monkey by intracerebral inoculation. With the known incubation periods in other TSEs, oral transmission studies of CWD may take much longer. Every victim/family of CJD/TSEs should be asked about route and source of this agent. To prolong this will only spread the agent and needlessly expose others. In light of the findings of Asante and Collinge et al, there should be drastic measures to safeguard the medical and surgical arena from sporadic CJDs and all human TSEs. I only ponder how many sporadic CJDs in the USA are type 2 PrPSc?
https://www.neurology.org/doi/10.1212/01.WNL.0000036913.87823.D6
14th ICID International Scientific Exchange Brochure -
Final Abstract Number: ISE.114
Session: International Scientific Exchange
Transmissible Spongiform encephalopathy (TSE) animal and human TSE in North America
update October 2009
T. Singeltary
Bacliff, TX, USA
Background:
An update on atypical BSE and other TSE in North America. Please remember, the typical U.K. c-BSE, the atypical l-BSE (BASE), and h-BSE have all been documented in North America, along with the typical scrapie's, and atypical Nor-98 Scrapie, and to date, 2 different strains of CWD, and also TME. All these TSE in different species have been rendered and fed to food producing animals for humans and animals in North America (TSE in cats and dogs ?), and that the trading of these TSEs via animals and products via the USA and Canada has been immense over the years, decades.
Methods:
12 years independent research of available data
Results:
I propose that the current diagnostic criteria for human TSEs only enhances and helps the spreading of human TSE from the continued belief of the UKBSEnvCJD only theory in 2009. With all the science to date refuting it, to continue to validate this old myth, will only spread this TSE agent through a multitude of potential routes and sources i.e. consumption, medical i.e., surgical, blood, dental, endoscopy, optical, nutritional supplements, cosmetics etc.
Conclusion:
I would like to submit a review of past CJD surveillance in the USA, and the urgent need to make all human TSE in the USA a reportable disease, in every state, of every age group, and to make this mandatory immediately without further delay. The ramifications of not doing so will only allow this agent to spread further in the medical, dental, surgical arena's. Restricting the reporting of CJD and or any human TSE is NOT scientific. Iatrogenic CJD knows NO age group, TSE knows no boundaries. I propose as with Aguzzi, Asante, Collinge, Caughey, Deslys, Dormont, Gibbs, Gajdusek, Ironside, Manuelidis, Marsh, et al and many more, that the world of TSE Transmissible Spongiform Encephalopathy is far from an exact science, but there is enough proven science to date that this myth should be put to rest once and for all, and that we move forward with a new classification for human and animal TSE that would properly identify the infected species, the source species, and then the route.
http://ww2.isid.org/Downloads/14th_ICID_ISE_Abstracts.pdf
archived url;
https://web.archive.org/web/20100216162542/http://ww2.isid.org/Downloads/14th_ICID_ISE_Abstracts.pdf
International Society for Infectious Diseases Web: http://www.isid.org
http://prionunitusaupdate2008.blogspot.com/2010/01/human-prion-diseases-in-united-states.html
my comments to PLosone here ;
https://web.archive.org/web/20100408021509/http://www.plosone.org/annotation/listThread.action?inReplyTo=info%3Adoi%2F10.1371%2Fannotation%2F04ce2b24-613d-46e6-9802-4131e2bfa6fd&root=info%3Adoi%2F10.1371%2Fannotation%2F04ce2b24-613d-46e6-9802-4131e2bfa6fd
Wednesday, February 24, 2010
Transmissible Spongiform encephalopathy (TSE) animal and human TSE in North America 14th
ICID International Scientific Exchange Brochure -
http://transmissiblespongiformencephalopathy.blogspot.com/2010/02/transmissible-spongiform-encephalopathy.html
2023
https://creutzfeldt-jakob-disease.blogspot.com/2023/09/professor-john-collinge-on-tackling.html
***> NOW think iatrogenic TSE PrP transmission to humans from exposure to Cervid CWD TSE PrP, what if?
all iatrogenic cjd is, is sporadic cjd, before the iatrogenic event is discovered, traced back, proven, documented, put into the academic domain, and then finally the public domain, this very seldom happens, thus problem solved, it's all sporadic cjd.
Transmissible Spongiform encephalopathy (TSE) animal and human TSE in North America 14th
ICID International Scientific Exchange Brochure -
http://transmissiblespongiformencephalopathy.blogspot.com/2010/02/transmissible-spongiform-encephalopathy.html
2023
https://creutzfeldt-jakob-disease.blogspot.com/2023/09/professor-john-collinge-on-tackling.html
***> NOW think iatrogenic TSE PrP transmission to humans from exposure to Cervid CWD TSE PrP, what if?
all iatrogenic cjd is, is sporadic cjd, before the iatrogenic event is discovered, traced back, proven, documented, put into the academic domain, and then finally the public domain, this very seldom happens, thus problem solved, it's all sporadic cjd.
iatrogenic Transmissible Spongiform Encephalopathy
https://itseprion.blogspot.com/
least we forget...
*** Transmission of Creutzfeldt-Jakob disease to a chimpanzee by electrodes contaminated during neurosurgery ***
Gibbs CJ Jr, Asher DM, Kobrine A, Amyx HL, Sulima MP, Gajdusek DC.
Laboratory of Central Nervous System Studies, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892. Stereotactic multicontact electrodes used to probe the cerebral cortex of a middle aged woman with progressive dementia were previously implicated in the accidental transmission of Creutzfeldt-Jakob disease (CJD) to two younger patients. The diagnoses of CJD have been confirmed for all three cases. More than two years after their last use in humans, after three cleanings and repeated sterilisation in ethanol and formaldehyde vapour, the electrodes were implanted in the cortex of a chimpanzee. Eighteen months later the animal became ill with CJD. This finding serves to re-emphasise the potential danger posed by reuse of instruments contaminated with the agents of spongiform encephalopathies, even after scrupulous attempts to clean them.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8006664&dopt=Abstract
least we forget...
*** Transmission of Creutzfeldt-Jakob disease to a chimpanzee by electrodes contaminated during neurosurgery ***
Gibbs CJ Jr, Asher DM, Kobrine A, Amyx HL, Sulima MP, Gajdusek DC.
Laboratory of Central Nervous System Studies, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892. Stereotactic multicontact electrodes used to probe the cerebral cortex of a middle aged woman with progressive dementia were previously implicated in the accidental transmission of Creutzfeldt-Jakob disease (CJD) to two younger patients. The diagnoses of CJD have been confirmed for all three cases. More than two years after their last use in humans, after three cleanings and repeated sterilisation in ethanol and formaldehyde vapour, the electrodes were implanted in the cortex of a chimpanzee. Eighteen months later the animal became ill with CJD. This finding serves to re-emphasise the potential danger posed by reuse of instruments contaminated with the agents of spongiform encephalopathies, even after scrupulous attempts to clean them.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8006664&dopt=Abstract
why do we not want to do TSE transmission studies on chimpanzees $
snip...
5. A positive result from a chimpanzee challenged severly would likely create alarm in some circles even if the result could not be interpreted for man. I have a view that all these agents could be transmitted provided a large enough dose by appropriate routes was given and the animals kept long enough. Until the mechanisms of the species barrier are more clearly understood it might be best to retain that hypothesis.
snip...
R. BRADLEY
is this what we leave our Children and Grandchildren?
Prion Diseases Toolbox Prion Diseases Toolbox for biosafety/biosecurity professionals: current and relevant resources compiled from organizations, government agencies, and news outlets
Terry S. Singeltary Sr.
posted by Terry S. Singeltary Sr. at
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