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) Only registered and activated users can see links., Click Here To Register...
Abstract Publication History Information & Authors Metrics & Citations Share Abstract
Objective:
This study presents a cluster of Creutzfeldt-Jakob disease (CJD) cases after exposure to chronic wasting disease (CWD)-infected deer, suggestive of potential prion transmission from CWD-infected deer to humans.
Background:
CJD is a rapidly progressive central nervous system disorder caused by misfolded prion proteins. CWD, a prion disease prevalent in North American deer, has raised concerns due to its possible link to CJD. Although no conclusive evidence of cross-species prion transmission exists, vigilance for such cases is crucial for public health.
Design/Methods:
Not applicable.
Results:
In 2022, a 72-year-old man with a history of consuming meat from a CWD-infected deer population presented with rapid-onset confusion and aggression. His friend, who had also eaten venison from the same deer population, recently died of CJD, raising concerns about a potential link between CWD and human prion disease. Despite aggressive symptomatic treatment of seizures and agitation, the patient’s condition deteriorated and he died within a month of initial presentation. The diagnosis was confirmed postmortem as sporadic CJD with homozygous methionine at codon 129 (sCJDMM1). The patient’s history, including a similar case in his social group, suggests a possible novel animal-to-human transmission of CWD. Based on non-human primate and mouse models, cross-species transmission of CJD is plausible. Due to the challenge of distinguishing sCJDMM1 from CWD without detailed prion protein characterization, it is not possible to definitively rule out CWD in these cases. Although causation remains unproven, this cluster emphasizes the need for further investigation into the potential risks of consuming CWD-infected deer and its implications for public health.
Conclusions:
Clusters of sporadic CJD cases may occur in regions with CWD-confirmed deer populations, hinting at potential cross-species prion transmission. Surveillance and further research are essential to better understand this possible association.
Disclosure: Mr. Trout has nothing to disclose. Dr. Roberts has nothing to disclose. Dr. Tabet has nothing to disclose. Dr. Kotkowski has nothing to disclose. Dr. Horn has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Cala Trio. The institution of Dr. Horn has received research support from Alzheimer's Association.
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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.
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''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.''
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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.net Ref: 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 ;
Only registered and activated users can see links., Click Here To Register....
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
PART 2. TPWD CHAPTER 65. DIVISION 1. CWD
31 TAC §§65.82, 65.85, 65.88
The Texas Parks and Wildlife Commission in a duly noticed meeting on May 25, 2023 adopted amendments to 31 TAC §§65.82, 65.85, and §65.88, concerning Disease Detection and Response, without changes to the proposed text as published in the April 21, 2023, issue of the Texas Register (48 TexReg 2048). The rules will not be republished.
Currently, there is scientific evidence to suggest that CWD has zoonotic potential; however, no confirmed cases of CWD have been found in humans.
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17 DETECTION OF CHRONIC WASTING DISEASE PRIONS IN PROCESSED MEATS.
Rebeca Benavente1, Francisca Bravo1,2, Paulina Soto1,2, J. Hunter Reed3, Mitch Lockwood3, Rodrigo Morales1,2
1Department of Neurology, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, USA. 2Universidad Bernardo O’Higgins, Santiago, Chile. 3Texas Parks and Wildlife, Austin, USA
Abstract
The zoonotic potential of chronic wasting disease (CWD) remains unknown. Currently, there are no known natural cases of CWD transmission to humans but increasing evidence suggests that the host range of CWD is not confined only to cervid species. Alarmingly, recent experimental evidence suggests that certain CWD isolates can induce disease in non-human primates. While the CDC strongly recommends determining CWD status in animals prior to consumption, this practice is voluntary. Consequently, it is plausible that a proportion of the cervid meat entering the human food chain may be contaminated with CWD. Of additional concern is that traditional diagnostic techniques used to detect CWD have relatively low sensitivity and are only approved for use in tissues other than those typically ingested by humans. 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.
=====
9 Carrot plants as potential vectors for CWD transmission.
Paulina Soto1,2, Francisca Bravo-Risi1,2, Claudio Soto1, Rodrigo Morales1,2
1Department of Neurology, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, USA. 2Universidad Bernardo O’Higgins, Santiago, Chile
***> We show that edible plant components can absorb prions from CWD-contaminated soils and transport them to their aerial parts.
***> Our results indicate that edible plants could participate as vectors of CWD transmission
=====
Transmission of prion infectivity from CWD-infected 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
***> 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
=====
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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 tg650 mice intracerebrally with two deer CWD isolates, Wisc-1 and 116AG [22, 23, 27, 29]. We demonstrate that this transgenic line was susceptible to infection with CWD prions and displayed a distinct leading clinical sign, an atypical PrPSc signature and unusual fecal shedding of infectious prions. Importantly, these prions generated by the human PrP transgenic mice were transmissible upon passage. Our results are the first evidence of a zoonotic risk of CWD when using one of the most common CWD strains, Wisc-1/CWD1 for infection. We demonstrated in a human transgenic mouse model that the species barrier for transmission of CWD to humans is not absolute. The fact that its signature was not typical raises the questions whether CWD would manifest in humans as a subclinical infection, whether it would arise through direct or indirect transmission including an intermediate host, or a silent to uncovered human-to-human transmission, and whether current detection techniques will be suffcient to unveil its presence.
Our findings strongly suggest that CWD should be regarded as an actual public health risk. Here, we use humanized mice to show that CWD prions can cross the species barrier to humans, and remarkably, infectious prions can be excreted in feces.
Our results indicate that if CWD crosses the species-barrier to humans, it is unlikely to resemble the most common forms of human prion diseases with respect to clinical signs, tissue tropism and PrPSc signature. For instance, PrPSc in variable protease-sensitive prionopathy (VPSPr), a sporadic form of human prion disease, and in the genetic form Gerstmann-Sträussler-Scheinker syndrome (GSS) is defined by an atypical PK-resistant PrPSc fragment that is non-glycosylated and truncated at both C- and N-termini, with a molecular weight between 6 and 8 kDa [24, 44–46]. These biochemical features are unique and distinctive from PrPSc (PrP27-30) found in most other human or animal prion disease. The atypical PrPSc signature detected in brain homogenate of tg650 mice #321 (1st passage) and #3063 (2nd passage), and the 7–8 kDa fragment (Figs. 2, 4) are very similar to that of GSS, both in terms of migration profile and the N-terminal cleavage site.
CWD in humans might remain subclinical but with PrPSc deposits in the brain with an unusual morphology that does not resemble the patterns usually seen in different prion diseases (e.g., mouse #328; Fig. 3), clinical with untraceable abnormal PrP (e.g., mouse #327) but still transmissible and uncovered upon subsequent passage (e.g., mouse #3063; Fig. 4), or prions have other reservoirs than the usual ones, hence the presence of infectivity in feces (e.g., mouse #327) suggesting a potential for human-to-human transmission and a real iatrogenic risk that might be unrecognizable.
suggesting a potential for human-to-human transmission and a real iatrogenic risk that might be unrecognizable.
=================================
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Fortuitous generation of a zoonotic cervid prion strain
Manuel Camacho, Xu Qi, Liuting Qing, Sydney Smith, Jieji Hu, Wanyun Tao, Ignazio Cali, Qingzhong Kong. Department of Pathology, Case Western Reserve University, Cleveland, USA
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 Tg12 mice 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 Tg12 mice. 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.
Funded by: NIH Grant number: R01NS052319, R01NS088604, R01NS109532
Acknowledgement: We want to thank the National Prion Disease Pathology Surveillance Center and Drs. Allen Jenny and Katherine O'Rourke for providing the sCJD samples and the CWD samples used in this study, respectively
"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."
PRION 2023 CONTINUED;
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ARS RESEARCH Generation of human chronic wasting disease in transgenic mice
Publication Acceptance Date: 9/8/2021
Research Project: Pathobiology, Genetics, and Detection of Transmissible Spongiform Encephalopathies Location: Virus and Prion Research
Title: Generation of human chronic wasting disease in transgenic mice
Author item WANG, ZERUI - Case Western Reserve University (CWRU) item QIN, KEFENG - University Of Chicago item CAMACHO, MANUEL - Case Western Reserve University (CWRU) item SHEN, PINGPING - Case Western Reserve University (CWRU) item YUAN, JUE - Case Western Reserve University (CWRU) item Greenlee, Justin item CUI, LI - Jilin University item KONG, QINGZHONG - Case Western Reserve University (CWRU) item MASTRIANNI, JAMES - University Of Chicago item ZOU, WEN-QUAN - Case Western Reserve University (CWRU)
Submitted to: Acta Neuropathologica Publication Type: Peer Reviewed Journal Publication Acceptance Date: 9/8/2021 Publication Date: N/A Citation: N/A
Interpretive Summary: Prion diseases are invariably fatal neurologic diseases for which there is no known prevention or cure. Chronic wasting disease (CWD) is the prion disease of deer and elk and is present in farmed and free ranging herds throughout North America. To date there is no clear evidence that the CWD agent could be transmitted to humans. This manuscript describes the use of an in vitro technique, cell-free serial protein misfolding cyclic amplification (sPMCA), to generate a CWD prion that is infectious to transgenic mice expressing the human prion protein. This study provides the first evidence that CWD prions may be able to cause misfolding in the human prion protein. This information will impact medical experts and those involved in making policy for farmed cervids and wildlife.
Technical Abstract: Chronic wasting disease (CWD) is a cervid spongiform encephalopathy or prion disease caused by the infectious prion or PrPSc, a misfolded conformer of cellular prion protein (PrPC). It has rapidly spread in North America and also has been found in Asia and Europe. In contrast to the zoonotic mad cow disease that is the first animal prion disease found transmissible to humans, the transmissibility of CWD to humans remains uncertain although most previous studies have suggested that humans may not be susceptible to CWD. Here we report the generation of an infectious human PrPSc by seeding CWD PrPSc in normal human brain PrPC through the in vitro cell-free serial protein misfolding cyclic amplification (sPMCA). Western blotting confirms that the sPMCA-induced proteinase K-resistant PrPSc is a human form, evidenced by a PrP-specific antibody that recognizes human but not cervid PrP. Remarkably, two lines of humanized transgenic (Tg) mice expressing human PrP-129Val/Val (VV) or -129Met/Met (MM) polymorphism develop prion disease at 233 ± 6 (mean ± SE) days post-inoculation (dpi) and 552 ± 27 dpi, respectively, upon intracerebral inoculation with the sPMCA-generated PrPSc. The brain of diseased Tg mice reveals the electrophoretic profile of PrPSc similar to sporadic Creutzfeldt-Jakob disease (sCJD) MM1 or VV2 subtype but different neuropathological patterns. We believe that our study provides the first evidence that CWD PrPSc is able to convert human PrPC into PrPSc in vitro and the CWD-derived human PrPSc mimics atypical sCJD subtypes in humanized Tg mice.
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''The brain of diseased Tg mice reveals the electrophoretic profile of PrPSc similar to sporadic Creutzfeldt-Jakob disease (sCJD) MM1 or VV2 subtype but different neuropathological patterns.''
''We believe that our study provides the first evidence that CWD PrPSc is able to convert human PrPC into PrPSc in vitro and the CWD-derived human PrPSc mimics atypical sCJD subtypes in humanized Tg mice.''
SATURDAY, APRIL 20, 2024
Chronic Wasting Disease CWD TSE Prion of Cervid Zoonosis to humans, iatrogenic transmission, what if 2024?
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(P7-13.002) Jonathan Trout, Matthew Roberts, Michel Tabet, Eithan Kotkowski, and Sarah HornAUTHORS INFO & AFFILIATIONS April 9, 2024 issue 102 (17_supplement_1) Only registered and activated users can see links., Click Here To Register...
Abstract Publication History Information & Authors Metrics & Citations Share Abstract
Objective:
This study presents a cluster of Creutzfeldt-Jakob disease (CJD) cases after exposure to chronic wasting disease (CWD)-infected deer, suggestive of potential prion transmission from CWD-infected deer to humans.
Background:
CJD is a rapidly progressive central nervous system disorder caused by misfolded prion proteins. CWD, a prion disease prevalent in North American deer, has raised concerns due to its possible link to CJD. Although no conclusive evidence of cross-species prion transmission exists, vigilance for such cases is crucial for public health.
Design/Methods:
Not applicable.
Results:
In 2022, a 72-year-old man with a history of consuming meat from a CWD-infected deer population presented with rapid-onset confusion and aggression. His friend, who had also eaten venison from the same deer population, recently died of CJD, raising concerns about a potential link between CWD and human prion disease. Despite aggressive symptomatic treatment of seizures and agitation, the patient’s condition deteriorated and he died within a month of initial presentation. The diagnosis was confirmed postmortem as sporadic CJD with homozygous methionine at codon 129 (sCJDMM1). The patient’s history, including a similar case in his social group, suggests a possible novel animal-to-human transmission of CWD. Based on non-human primate and mouse models, cross-species transmission of CJD is plausible. Due to the challenge of distinguishing sCJDMM1 from CWD without detailed prion protein characterization, it is not possible to definitively rule out CWD in these cases. Although causation remains unproven, this cluster emphasizes the need for further investigation into the potential risks of consuming CWD-infected deer and its implications for public health.
Conclusions:
Clusters of sporadic CJD cases may occur in regions with CWD-confirmed deer populations, hinting at potential cross-species prion transmission. Surveillance and further research are essential to better understand this possible association.
Disclosure: Mr. Trout has nothing to disclose. Dr. Roberts has nothing to disclose. Dr. Tabet has nothing to disclose. Dr. Kotkowski has nothing to disclose. Dr. Horn has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Cala Trio. The institution of Dr. Horn has received research support from Alzheimer's Association.
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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.
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''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.''
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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.net Ref: 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 ;
Only registered and activated users can see links., Click Here To Register....
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
PART 2. TPWD CHAPTER 65. DIVISION 1. CWD
31 TAC §§65.82, 65.85, 65.88
The Texas Parks and Wildlife Commission in a duly noticed meeting on May 25, 2023 adopted amendments to 31 TAC §§65.82, 65.85, and §65.88, concerning Disease Detection and Response, without changes to the proposed text as published in the April 21, 2023, issue of the Texas Register (48 TexReg 2048). The rules will not be republished.
Currently, there is scientific evidence to suggest that CWD has zoonotic potential; however, no confirmed cases of CWD have been found in humans.
Only registered and activated users can see links., Click Here To Register...
17 DETECTION OF CHRONIC WASTING DISEASE PRIONS IN PROCESSED MEATS.
Rebeca Benavente1, Francisca Bravo1,2, Paulina Soto1,2, J. Hunter Reed3, Mitch Lockwood3, Rodrigo Morales1,2
1Department of Neurology, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, USA. 2Universidad Bernardo O’Higgins, Santiago, Chile. 3Texas Parks and Wildlife, Austin, USA
Abstract
The zoonotic potential of chronic wasting disease (CWD) remains unknown. Currently, there are no known natural cases of CWD transmission to humans but increasing evidence suggests that the host range of CWD is not confined only to cervid species. Alarmingly, recent experimental evidence suggests that certain CWD isolates can induce disease in non-human primates. While the CDC strongly recommends determining CWD status in animals prior to consumption, this practice is voluntary. Consequently, it is plausible that a proportion of the cervid meat entering the human food chain may be contaminated with CWD. Of additional concern is that traditional diagnostic techniques used to detect CWD have relatively low sensitivity and are only approved for use in tissues other than those typically ingested by humans. 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.
=====
9 Carrot plants as potential vectors for CWD transmission.
Paulina Soto1,2, Francisca Bravo-Risi1,2, Claudio Soto1, Rodrigo Morales1,2
1Department of Neurology, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, USA. 2Universidad Bernardo O’Higgins, Santiago, Chile
***> We show that edible plant components can absorb prions from CWD-contaminated soils and transport them to their aerial parts.
***> Our results indicate that edible plants could participate as vectors of CWD transmission
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Transmission of prion infectivity from CWD-infected 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
***> 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
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Transmission of cervid prions to humanized mice demonstrates the zoonotic potential of CWD
Samia Hannaoui1 · Irina Zemlyankina1 · Sheng Chun Chang1 · Maria Immaculata Arifn1 · Vincent Béringue2 · Debbie McKenzie3 · Hermann M. Schatzl1 · Sabine Gilch1
Received: 24 May 2022 / Revised: 5 August 2022 / Accepted: 7 August 2022
© The Author(s) 2022
Abstract
Prions cause infectious and fatal neurodegenerative diseases in mammals. Chronic wasting disease (CWD), a prion disease of cervids, spreads efficiently among wild and farmed animals. Potential transmission to humans of CWD is a growing concern due to its increasing prevalence. Here, we provide evidence for a zoonotic potential of CWD prions, and its probable signature using mice expressing human prion protein (PrP) as an infection model. Inoculation of these mice with deer CWD isolates resulted in atypical clinical manifestation with prion seeding activity and efficient transmissible infectivity in the brain and, remarkably, in feces, but without classical neuropathological or Western blot appearances of prion diseases. Intriguingly, the protease-resistant PrP in the brain resembled that found in a familial human prion disease and was transmissible upon second passage. Our results suggest that CWD might infect humans, although the transmission barrier is likely higher compared to zoonotic transmission of cattle prions. Notably, our data suggest a different clinical presentation, prion signature, and tissue tropism, which causes challenges for detection by current diagnostic assays. Furthermore, the presence of infectious prions in feces is concerning because if this occurs in humans, it is a source for human-to-human transmission. These findings have strong implications for public health and CWD management.
Keywords Chronic wasting disease · CWD · Zoonotic potential · Prion strains · Zoonotic prions
HIGHLIGHTS OF THIS STUDY
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Our results suggest that CWD might infect humans, although the transmission barrier is likely higher compared to zoonotic transmission of cattle prions. Notably, our data suggest a different clinical presentation, prion signature, and tissue tropism, which causes challenges for detection by current diagnostic assays. Furthermore, the presence of infectious prions in feces is concerning because if this occurs in humans, it is a source for human-to-human transmission. These findings have strong implications for public health and CWD management.
In this study, we evaluated the zoonotic potential of CWD using a transgenic mouse model overexpressing human M129-PrPC (tg650 [12]). We inoculated tg650 mice intracerebrally with two deer CWD isolates, Wisc-1 and 116AG [22, 23, 27, 29]. We demonstrate that this transgenic line was susceptible to infection with CWD prions and displayed a distinct leading clinical sign, an atypical PrPSc signature and unusual fecal shedding of infectious prions. Importantly, these prions generated by the human PrP transgenic mice were transmissible upon passage. Our results are the first evidence of a zoonotic risk of CWD when using one of the most common CWD strains, Wisc-1/CWD1 for infection. We demonstrated in a human transgenic mouse model that the species barrier for transmission of CWD to humans is not absolute. The fact that its signature was not typical raises the questions whether CWD would manifest in humans as a subclinical infection, whether it would arise through direct or indirect transmission including an intermediate host, or a silent to uncovered human-to-human transmission, and whether current detection techniques will be suffcient to unveil its presence.
Our findings strongly suggest that CWD should be regarded as an actual public health risk. Here, we use humanized mice to show that CWD prions can cross the species barrier to humans, and remarkably, infectious prions can be excreted in feces.
Our results indicate that if CWD crosses the species-barrier to humans, it is unlikely to resemble the most common forms of human prion diseases with respect to clinical signs, tissue tropism and PrPSc signature. For instance, PrPSc in variable protease-sensitive prionopathy (VPSPr), a sporadic form of human prion disease, and in the genetic form Gerstmann-Sträussler-Scheinker syndrome (GSS) is defined by an atypical PK-resistant PrPSc fragment that is non-glycosylated and truncated at both C- and N-termini, with a molecular weight between 6 and 8 kDa [24, 44–46]. These biochemical features are unique and distinctive from PrPSc (PrP27-30) found in most other human or animal prion disease. The atypical PrPSc signature detected in brain homogenate of tg650 mice #321 (1st passage) and #3063 (2nd passage), and the 7–8 kDa fragment (Figs. 2, 4) are very similar to that of GSS, both in terms of migration profile and the N-terminal cleavage site.
CWD in humans might remain subclinical but with PrPSc deposits in the brain with an unusual morphology that does not resemble the patterns usually seen in different prion diseases (e.g., mouse #328; Fig. 3), clinical with untraceable abnormal PrP (e.g., mouse #327) but still transmissible and uncovered upon subsequent passage (e.g., mouse #3063; Fig. 4), or prions have other reservoirs than the usual ones, hence the presence of infectivity in feces (e.g., mouse #327) suggesting a potential for human-to-human transmission and a real iatrogenic risk that might be unrecognizable.
suggesting a potential for human-to-human transmission and a real iatrogenic risk that might be unrecognizable.
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Fortuitous generation of a zoonotic cervid prion strain
Manuel Camacho, Xu Qi, Liuting Qing, Sydney Smith, Jieji Hu, Wanyun Tao, Ignazio Cali, Qingzhong Kong. Department of Pathology, Case Western Reserve University, Cleveland, USA
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 Tg12 mice 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 Tg12 mice. 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.
Funded by: NIH Grant number: R01NS052319, R01NS088604, R01NS109532
Acknowledgement: We want to thank the National Prion Disease Pathology Surveillance Center and Drs. Allen Jenny and Katherine O'Rourke for providing the sCJD samples and the CWD samples used in this study, respectively
"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."
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ARS RESEARCH Generation of human chronic wasting disease in transgenic mice
Publication Acceptance Date: 9/8/2021
Research Project: Pathobiology, Genetics, and Detection of Transmissible Spongiform Encephalopathies Location: Virus and Prion Research
Title: Generation of human chronic wasting disease in transgenic mice
Author item WANG, ZERUI - Case Western Reserve University (CWRU) item QIN, KEFENG - University Of Chicago item CAMACHO, MANUEL - Case Western Reserve University (CWRU) item SHEN, PINGPING - Case Western Reserve University (CWRU) item YUAN, JUE - Case Western Reserve University (CWRU) item Greenlee, Justin item CUI, LI - Jilin University item KONG, QINGZHONG - Case Western Reserve University (CWRU) item MASTRIANNI, JAMES - University Of Chicago item ZOU, WEN-QUAN - Case Western Reserve University (CWRU)
Submitted to: Acta Neuropathologica Publication Type: Peer Reviewed Journal Publication Acceptance Date: 9/8/2021 Publication Date: N/A Citation: N/A
Interpretive Summary: Prion diseases are invariably fatal neurologic diseases for which there is no known prevention or cure. Chronic wasting disease (CWD) is the prion disease of deer and elk and is present in farmed and free ranging herds throughout North America. To date there is no clear evidence that the CWD agent could be transmitted to humans. This manuscript describes the use of an in vitro technique, cell-free serial protein misfolding cyclic amplification (sPMCA), to generate a CWD prion that is infectious to transgenic mice expressing the human prion protein. This study provides the first evidence that CWD prions may be able to cause misfolding in the human prion protein. This information will impact medical experts and those involved in making policy for farmed cervids and wildlife.
Technical Abstract: Chronic wasting disease (CWD) is a cervid spongiform encephalopathy or prion disease caused by the infectious prion or PrPSc, a misfolded conformer of cellular prion protein (PrPC). It has rapidly spread in North America and also has been found in Asia and Europe. In contrast to the zoonotic mad cow disease that is the first animal prion disease found transmissible to humans, the transmissibility of CWD to humans remains uncertain although most previous studies have suggested that humans may not be susceptible to CWD. Here we report the generation of an infectious human PrPSc by seeding CWD PrPSc in normal human brain PrPC through the in vitro cell-free serial protein misfolding cyclic amplification (sPMCA). Western blotting confirms that the sPMCA-induced proteinase K-resistant PrPSc is a human form, evidenced by a PrP-specific antibody that recognizes human but not cervid PrP. Remarkably, two lines of humanized transgenic (Tg) mice expressing human PrP-129Val/Val (VV) or -129Met/Met (MM) polymorphism develop prion disease at 233 ± 6 (mean ± SE) days post-inoculation (dpi) and 552 ± 27 dpi, respectively, upon intracerebral inoculation with the sPMCA-generated PrPSc. The brain of diseased Tg mice reveals the electrophoretic profile of PrPSc similar to sporadic Creutzfeldt-Jakob disease (sCJD) MM1 or VV2 subtype but different neuropathological patterns. We believe that our study provides the first evidence that CWD PrPSc is able to convert human PrPC into PrPSc in vitro and the CWD-derived human PrPSc mimics atypical sCJD subtypes in humanized Tg mice.
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''The brain of diseased Tg mice reveals the electrophoretic profile of PrPSc similar to sporadic Creutzfeldt-Jakob disease (sCJD) MM1 or VV2 subtype but different neuropathological patterns.''
''We believe that our study provides the first evidence that CWD PrPSc is able to convert human PrPC into PrPSc in vitro and the CWD-derived human PrPSc mimics atypical sCJD subtypes in humanized Tg mice.''
SATURDAY, APRIL 20, 2024
Chronic Wasting Disease CWD TSE Prion of Cervid Zoonosis to humans, iatrogenic transmission, what if 2024?
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