Thursday, April 10, 2025

CWD TSE Prion, Politics, Friendly Fire, Unforeseen Consequences, What If?

CWD TSE Prion, Politics, Friendly Fire, Unforeseen Consequences, What If?

Chronic wasting disease (CWD) prion detection in environmental and biological samples from a taxidermy site and nursing facility, and instruments used in surveillance activities

Paulina Soto a b , Nancy Ho a , Mitch Lockwood c , Austin Stolte c , J. Hunter Reed c , Rodrigo Morales a b

a Department of Neurology, The University of Texas Health Science Center at Houston, Houston, TX, United States of America

b Centro Integrativo de Biologia y Quimica Aplicada (CIBQA), Universidad Bernardo O'Higgins, Santiago, Chile

c Texas Parks and Wildlife Department (TPWD), Kerrville, TX, United States of America

Received 20 September 2024, Revised 27 February 2025, Accepted 31 March 2025, Available online 9 April 2025, Version of Record 9 April 2025.


Highlights

• CWD prions were identified in a taxidermy and deer nursing facility.

• Contaminated samples included waters, soils, dermestid beetles, domestic flies and a dumpster.

• Surgical instruments used to collect deer samples can get contaminated with CWD prions.

• Some of the infectious particles are readily released from surgical instruments when washed.

• Our results suggest that taxidermy practices actively contribute in the spreading of CWD.

Abstract

Chronic wasting disease (CWD) is a transmissible prionopathy affecting free-ranging and captive cervids. CWD is thought to spread through both direct and indirect transmission mechanisms. Along this line, human activities have not been thoroughly explored for their potential to spread this disease. One area of concern involves taxidermy procedures and surveillance activities as handled animals or carcasses are of unknown CWD statuses. Worrisomely, taxidermy facilities can act as foci of prion infectivity if appropriate biosecurity practices are not implemented. In this study, we evaluated the presence of infectious prions in a taxidermy facility that was possibly exposed to CWD prions. To determine this, we collected biological and environmental specimens from this site and screened them using the protein misfolding cyclic amplification (PMCA) technique. Additionally, we swabbed different surfaces possibly exposed to CWD-infected animals or carcasses. We report the presence of prions in i) waters used to digest tissues from deer carcasses, ii) soils that were in contact with the previously mentioned waters, iii) dermestid beetles used to clean skulls, iv) other insects found in the beetle shed, and iv) dumpsters where animal carcasses were disposed. Additionally, we report that surgical materials used in surveillance practices may also hold CWD prions, even after being washed with aqueous solutions. All these results suggest that CWD prions may be disseminated due to human practices and that protocols should be established to decontaminate potentially contaminated materials.

Introduction

Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy that affects multiple cervid species, including mule deer, white-tailed deer, elk, reindeer, and moose, among others (Escobar et al., 2020). CWD is widely distributed in the United States and Canada in captive and free-ranging cervids. CWD is characterized by long incubation periods, followed by a relatively short clinical phase (Rivera et al., 2019; Williams, 2005). CWD is fatal in all cases when animals are clinical, and to date, there is no feasible treatment for curing either CWD or any other prion disease (Haley and Hoover, 2015). Unfortunately, CWD is rapidly expanding in both number of animals affected and geographical areas (Bartz et al., 2024; National Wildlife Health Center, 2025). Considering this, efficient containment and diagnostic testing strategies are urgently needed.

CWD can spread within animal populations with relative ease (Otero et al., 2021). The propagation of this disease is thought to be more efficient in captive animals considering the higher animal densities found in these environments (Mathiason et al., 2009; Rivera et al., 2019; Bartelt-Hunt and Bartz, 2017; Zabel and Ortega, 2017). Nevertheless, CWD transmission is still highly efficient in free-ranging cervid populations. CWD transmission is thought to occur mostly through direct animal contacts, or indirectly through the exposure of naïve animals to contaminated environments (Denkers et al., 2013; Escobar et al., 2020; Haley et al., 2011; Mathiason et al., 2009; Miller Michael et al., 2004; Soto et al., 2024). Environmental components, including inert materials and living organisms, are thought to play relevant roles in the spread of CWD (Escobar et al., 2020; Jacobson et al., 2010a; Pritzkow et al., 2018). Different studies have shown that infectious prions can enter the environment through decaying carcasses from diseased animals (Soto et al., 2023), gestational tissues released during parturition (Bravo-Risi et al., 2021), saliva (Haley et al., 2011), and excreta (Bravo-Risi et al., 2023). Once released, prions can bind to soil and other natural and manmade components (Johnson et al., 2006; Smith et al., 2011) and become available to susceptible animals. Other organisms, including plants, predators, scavengers, parasites, insects, and annelids may also participate in these processes by interacting with contaminated environmental components or animal tissues (Carlson et al., 2023; Fischer et al., 2013; Inzalaco et al., 2023; Pritzkow et al., 2015; Soto et al., 2024). Overall, multiple components and processes are involved in CWD prion transmission and dissemination. However, most of them are understudied and/or assayed in laboratory-controlled conditions. As consequence, the specific contribution of each process/element in CWD environmental contamination is contentious.

An essential factor to consider in the spreading of CWD prions includes human activities (Mori et al., 2024). Along this line, regulatory agencies already implemented or are currently considering regulations in several of these activities including containment, animal processing, movement of animals, disposal of carcasses, and breeding practices, among others (Mateus-Pinilla et al., 2013; Mysterud and Edmunds, 2019). Although most of these practices have a potential for CWD transmission, their overall importance in CWD epidemiology is understudied. One example of this involves taxidermy procedures. Deer are regarded as one of the most popular game animals, generating a high economic output and involving various activities including deer breeding, taxidermy, meat processing, and others (Arnot et al., 2009; Bishop, 2004) (https://nri.tamu.edu/media/3968/economic-values-of-white-tailed-deer-in-texas-2022-survey-part-i.pdf). Hunters active in areas with reported CWD cases are requested to follow state, wildlife and public health recommendations (Carlson et al., 2018). In general, all agencies strongly suggest CWD animal testing before processing. Many hunters process game at private facilities and, because of no statutory authority or lack of awareness, CWD-relevant guidelines or rules may not exist for meat processing and taxidermy facilities despite their capacity to transmit CWD. Specifically, the movement of carcasses or carcasses parts from areas with a high CWD incidence to areas with little or no incidence may facilitate CWD introduction and spread. In addition, it should be considered that inappropriate disposal of carcasses and animal products may also contribute to the dissemination of this disease (Angers et al., 2009; Benestad et al., 2016). Considering the above-mentioned scenarios, proper surveillance of CWD and management of activities involving potentially infected animals and animal-derived products might help to contain it. If left unchecked, there could be profound negative impacts on human health and wildlife conservation.

In this study, we evaluated the presence of CWD prions in a taxidermy facility where deer heads are processed to prepare skull mounts. Analyses were made using the protein misfolding cyclic amplification (PMCA) technique in various biological and environmental samples. In addition, we also tested the persistence of CWD prions in surgical materials used in surveillance procedures. Our results show, for the first time, CWD-prion detection in a potentially exposed taxidermy facility. In addition, we also tested the persistence of CWD prions in surgical materials used in surveillance procedures. This information has important implications on several fronts of CWD research including environmental spreading, human-related practices, and exposure of humans to infectious animal prions.

Section snippets

Samples

The samples were collected from a taxidermy and free-ranging deer rehabilitation facility located on the same property in Val Verde County, Texas. Texas Parks and Wildlife Department (TPWD) staff were initially notified of a CWD clinical suspect on this property; this animal was ultimately euthanized and confirmed positive for CWD by the National Veterinary Services Laboratory on January 5th, 2020. Samples were collected from different areas on this property where deer heads were processed to Screening of CWD prions in environmental and processing elements from a taxidermy facility

The European mount technique is a widely utilized taxidermy practice aiming to produce a skull of an animal that is free of tissue. The first critical step in making a European mount is removing the flesh from the animal's head. This is achieved by removing the majority of the external flesh, eyeballs, ears, and the brain. Then, the de-meated skull is subjected to a maceration process using bacteria. The purpose of this step is to soften and degrade any remaining tissue on the skull. This Discussion

CWD continues expanding in distribution and prevalence in North America. Hence, an essential factor in limiting the spread of this disease is to monitor and contain infectivity foci. This has proven to be difficult considering the limited diagnostic tools available to effectively identify the CWD infectious agent (prions). Identifying and mitigating the negative role that anthropogenic activities have in promoting CWD transmission is an essential step in developing a prevention strategy. The Conclusion

In summary, the information provided in this report demonstrate how anthropogenic activities, specifically taxidermy practices, animal processing, and rehabilitation of CWD susceptible species, may facilitate CWD transmission through the environmental dissemination of CWD prions. This study, along with future research efforts characterizing the overall level of infectivity, provides relevant information on managing CWD and to control its rapid geographic expansion. …


***> This old study always brings to light the long term effects of a TSE in the environment…

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.


Saturday, December 18, 2021

Direct neural transmission of vCJD/BSE in macaque after finger incision

Second death in France in a laboratory working on prions

Creutzfeldt-Jakob disease has killed a person who handled this infectious agent at Inrae in Toulouse.

After a first death in 2019, a moratorium on work on this pathogen has been extended.

France issues moratorium on prion research after fatal brain disease strikes two lab workers


Iatrogenic TSE Prion, Friendly Fire, Unforeseen Circumstances


Vertical transmission of chronic wasting disease in free-ranging white-tailed deer populations

Audrey M. Sandoval, Amy V. Nalls, Erin E. McNulty, Nathaniel D. Denkers, Devon J. Trujillo, Zoe Olmstead, Ethan Barton, Jennifer R. Ballard, Daniel M. Grove, Jeremy S. Dennison, Natalie Stilwell, Christopher A. Cleveland, James M. Crum, Mark G. Ruder, Candace K. Mathiason doi: Vertical transmission of chronic wasting disease in free-ranging white-tailed deer populations

ABSTRACT

Chronic wasting disease (CWD) is a fatal neurodegenerative disease affecting cervids across North America, Northern Europe, and Asia. Disease transmission among cervids has historically been attributed to direct animal-to-animal contact with ‘secreta’ (saliva, blood, urine, and feces) containing the infectious agent, and indirect contact with the agent shed to the environment in these bodily components. Mounting evidence provides another mechanism of CWD transmission, that from mother-to-offspring, including during pregnancy (vertical transmission). Here we describe the detection of the infectious CWD agent and prion seeding in fetal and reproductive tissues collected from healthy-appearing free-ranging white-tailed deer (Odocoileus virginianus) from multiple U.S. states by mouse bioassay and in vitro prion amplification assays. This is the first report of the infectious agent in several in utero derived fetal and maternal-fetal reproductive tissues, providing evidence that CWD infections are propagated within gestational fetal tissues of white-tailed deer populations. This work confirms previous experimental and field findings in several cervid species supporting vertical transmission as a mechanism of CWD transmission and helps to further explain the facile dissemination of this disease among captive and free-ranging cervid populations.

snip…

Overall, this study describes the dissemination of CWD prions throughout tissues and birthing fluids of the pregnancy microenvironment demonstrating that offspring are routinely exposed to the infectious prion in-utero prior to parturition.


Protein misfolding cyclic amplification (PMCA) as an ultra-sensitive technique for the screening of CWD prions in different sample types.

Francisca Bravo-Risi1,2, Paulina Soto1,2, Rebeca Benavente1, Hunter Reed3, Mitch Lockwood3, Tracy A. Nichols4, Rodrigo Morales1,5 1Department of Neurology, The University of Texas Health Science Center at Houston, Houston, USA. 2Universidad Bernardo O’Higgins, Doctorado en Ciencias con Mención en Materiales Funcionales, Santiago, Chile. 3Texas Park and Wildlife Department, Austin, USA. 4Veterinary Services Cervid Health Program, United States Department of Agriculture, Animal and Plant Health Inspection Service, Fort Collins, USA. 5Centro Integrativo de Biologia y Quimica Aplicada (CIBQA), Universidad Bernardo O’Higgins, Santiago, Chile

Abstract

Chronic wasting disease (CWD) is a prion disease that affects farmed and free-ranging cervids. Currently, CWD status is ultimately confirmed in the brain and lymphoid tissues by immunohistochemistry (IHC). One limitation of IHC is its relatively poor sensitivity making it difficult to detect this disease early in the incubation period which can extend 1-3 years. Protein misfolding cyclic amplification (PMCA) and real-time quaking-induced conversion (RT-QuIC) are ultra-sensitive techniques that provide a means to detect CWD in early stages of the disease. PMCA mimics the self-propagation of infectious prions in vitro through multiple incubation-sonication cycles, increasing the number of prion particles present in a given sample. The detection of proteinase K (PK)-resistant PrPSc by PMCA has been performed in experimental and natural samples that may otherwise go undetected using traditional diagnostic techniques.

In this study, we highlight recent advances and contributions that our group has made detecting CWD-prions in animal and environmental samples collected from deer breeding and taxidermy facilities. Additionally, CWD-prions were detected in samples from hunter-harvested, free-ranging animals.

PMCA successfully detected CWD-prions in a diverse array of samples including blood, semen, feces, obex, retropharyngeal lymph node, fetuses (neural and peripheral tissues) and gestational tissues, parasites-insects, plants, compost-soil mixtures, and swabs from trash containers.

Importantly, our findings identified CWD in areas previously considered to be free of CWD. Overall, our findings demonstrate that PMCA is a powerful technique for the screening of biological and environmental samples, and it may prove useful as a CWD management and surveillance tool.


RESEARCH ARTICLE

In Vitro detection of Chronic Wasting Disease (CWD) prions in semen and reproductive tissues of white tailed deer bucks (Odocoileus virginianus)

Carlos Kramm, Ruben Gomez-Gutierrez, Claudio Soto, Glenn Telling, Tracy Nichols, Rodrigo Morales


Abstract

Chronic Wasting Disease (CWD) is a prion disease affecting several cervid species. Among them, white-tailed deer (WTD) are of relevance due to their value in farming and game hunting. The exact events involved in CWD transmission in captive and wild animals are still unclear. An unexplored mechanism of CWD spread involves transmissions through germplasm, such as semen. Surprisingly, the presence and load of CWD prions in semen and male sexual tissues from WTD has not been explored. Here, we described the detection of CWD prions in semen and sexual tissues of WTD bucks utilizing the Protein Misfolding Cyclic Amplification (PMCA) technology. Samples were obtained post-mortem from farmed pre-clinical, CWD positive WTD bucks possessing polymorphisms at position 96 of the PRNP gene. Our results show that overall CWD detection in these samples had a sensitivity of 59.3%, with a specificity of 97.2%. The data indicate that the presence of CWD prions in male sexual organs and fluids is prevalent in late stage, pre-clinical, CWD-infected WTD (80%-100% of the animals depending on the sample type analyzed). Our findings reveal the presence of CWD prions in semen and sexual tissues of prion infected WTD bucks. Future studies will be necessary to determine whether sexual contact and/or artificial inseminations are plausible means of CWD transmission in susceptible animal species. snip... In terms of disease transmission, the presence of prions in semen begs the question on whether sexual contact is plausible route of CWD transmission. A previous report showed that semen collected from rams at pre-clinical and clinical stages of prion disease did not infect scrapie-susceptible mice [34]. Our previous results in Syrian hamsters showed that sexual exposure of naïve females to 263K infected males was ineffective in transmitting disease [35]. Maternal transmission has also be presented as a viable mode of CWD transmission to offspring. Evidence derived from scrapie-infected sheep and experimentally infected muntjac deer provides direct evidence that offspring from infected dams and ewes are at higher risk of developing prion disease [16,36]. Considering the results presented in this article, the risk of CWD transmission via semen cannot be dismiss without further inquiry.

It is important to note that some semen samples tested in the current report showed PrPSc presence after only one PMCA round, suggesting that PrPSc content in semen of some animals may be relatively high. This is particularly relevant considering that tissues from male sexual organs inhibited PMCA performance. It remains unclear if vaginal exposure to CWD prions in semen is an effective route of transmission.

In summary, our results confirm the presence of CWD prions in semen and male sexual tissues in CWD-infected WTD. Future experiments in actual deer will determine whether CWD can be transmitted by breeding practices including sexual contacts or artificial inseminations. Infectivity studies in transgenic mice underway in our laboratory will determine the infectivity titers of some of the samples described in this study.



Successful transmission of the chronic wasting disease (CWD) agent to white-tailed deer by intravenous blood transfusion

Author links open overlay panelNajiba Mammadova a b, Eric Cassmann a b, Justin J. Greenlee a


Highlights

•The chronic wasting disease (CWD) agent efficiently transmits between white-tailed deer.

•Blood from CWD infected deer contains infectious prions.

•A single intravenous blood transfusion resulted in CWD transmission with an incubation of 25.6 months for the GG96 recipient.

•The GS96 recipient had a longer incubation of 43.6 months.


Published: 15 September 2021

Detection of CWD prions in naturally infected white-tailed deer fetuses and gestational tissues by PMCA

Francisca Bravo-Risi, Paulina Soto, Thomas Eckland, Robert Dittmar, Santiago Ramírez, Celso S. G. Catumbela, Claudio Soto, Mitch Lockwood, Tracy Nichols & Rodrigo Morales Scientific Reports volume 11, Article number: 18385 (2021) Cite this article

Abstract

Chronic wasting disease (CWD) is a prevalent prion disease affecting cervids. CWD is thought to be transmitted through direct animal contact or by indirect exposure to contaminated environmental fomites. Other mechanisms of propagation such as vertical and maternal transmissions have also been suggested using naturally and experimentally infected animals. Here, we describe the detection of CWD prions in naturally-infected, farmed white-tailed deer (WTD) fetal tissues using the Protein Misfolding Cyclic Amplification (PMCA) technique. Prion seeding activity was identified in a variety of gestational and fetal tissues. Future studies should demonstrate if prions present in fetuses are at sufficient quantities to cause CWD after birth. This data confirms previous findings in other animal species and furthers vertical transmission as a relevant mechanism of CWD dissemination.

Snip…

Here, we report the presence of seeding competent CWD prions in fetal tissues collected from naturally prion-infected farmed WTD does using PMCA. The results presented in this article confirm the presence of CWD prions in fetal tissues from naturally infected farmed WTD dams suggesting that CWD could be transferred from mother to offspring.

Snip…

Discussion CWD is rapidly expanding in both captive and wild cervid populations. While direct animal contact and environmental contamination provide reasonable explanations on how this disease is transmitted, evidence involving fetal infection and maternal exposure suggest that these routes may be relevant for disease transmission. Offspring from scrapie-infected sheep has been described as being at increased risk of developing prion disease32. Similar outcomes have been described for farmed elk41 and experimentally infected muntjac deer31. Relevant evidence supporting maternal-offspring CWD transmission include prion seeding activity identified in placenta and gestational fluids from pregnant elk and muntjac deer29,30. Importantly, prion detection has been identified in fetal tissues from elk30. Controlled experimental conditions in muntjac deer demonstrate that mother-to-offspring transmission is possible for CWD31. Our results show that fetal tissues collected from naturally infected CWD-positive asymptomatic farmed WTD females contain seeding competent prions. This suggests that mother-to-offspring prion transmission is a common feature of CWD across different cervid species.

In this report, we communicate the screening of 19 fetal and gestational tissues and fluids for the detection of CWD prions. Relevant CWD positive fetal tissues include liver, kidney, and lymphoid and reproductive tissues. The case of liver and kidney is interesting, as prion accumulation in these tissues is not observed by IHC in adult CWD-symptomatic animals5. The presence of CWD prions in fetuses’ sexual tissues is also interesting, especially considering our previous report showing that prion seeding activity is present in the testes of CWD-infected WTD bucks only at the late pre-symptomatic stages35. On the contrary, the identification of CWD prions in a large proportion of lymphoid tissues is in alignment with the expected pathophysiology of prions observed in adult animals2. This finding suggests that the tropism of infectious prions in lymphoid organs occurs even at fetal stages. However, the results presented in this article do not allow us to conclude whether CWD prions present in fetal tissues came from the mothers through circulation or were generated de novo in the fetuses. The poor detection of CWD prions in fetal brains strongly supports the idea that neuroinvasion (ergo, prion replication) does not occur at fetal stages.

PMCA can detect prions at sub-infectious levels34,42,43,44 and CWD prion amplification by PMCA is able to catch sub-infectious PrPSc quantities in the first round6,35. Whether CWD prions present in fetal tissues exist in quantities large enough to induce clinical CWD after birth cannot be concluded from our results. Previous results in goats show that embryo transfer from infected to naïve females failed to transmit prion disease to offspring28, suggesting that if prions in sheep and goat embryos contain prions, they are present in sub-infectious quantities. Nevertheless, it is important to acknowledge that embryos described in those studies were exposed to a prion-infected environment for a restricted time, and either prion absorption and replication by embryos may be limited. The latter assumption is supported by the fact that recipient females were not infected28. Nonetheless, similar studies in sheep demonstrated that in utero prion transmission is possible45. The presence of prion infectivity in mammary glands, colostrum and milk of sheep suggest that transmission can also occur after birth46,47,48,49. Future studies detecting prions in mammary glands and milk of deer does will help us to evaluate the different possible scenarios in which CWD can be transmitted from mother to offspring (i.e., in utero vs. milking/nursing). Research in this area is relevant considering that wild WTD CWD-positive does seems more likely to be parents compared to their CWD-negative counterparts50.

The results presented in this study show that CWD prions exist in WTD fetuses from naturally infected does. Whether prions in fetal tissues are enough to sustain infectivity after birth, as well as descriptions of the mechanisms governing mother-to-offspring CWD transmission in cervids, should be clarified in future studies. These studies should include the screening of larger number of samples collected from wild and farmed animals affected by different strains of CWD prions, bioassays in susceptible mice to measure infectivity titers, and controlled experiments using pregnant/CWD-infected WTD females.


Protein misfolding cyclic amplification (PMCA) as an ultra-sensitive technique for the screening of CWD prions in different sample types.

Abstract

PMCA successfully detected CWD-prions in a diverse array of samples including blood, semen, feces, obex, retropharyngeal lymph node, fetuses (neural and peripheral tissues) and gestational tissues, parasites-insects, plants, compost-soil mixtures, and swabs from trash containers.

Importantly, our findings identified CWD in areas previously considered to be free of CWD. Overall, our findings demonstrate that PMCA is a powerful technique for the screening of biological and environmental samples, and it may prove useful as a CWD management and surveillance tool.


P74 High Prevalence of CWD prions in male reproductive samples

The results showed positive CWD prion detection in testes, epididymis and seminal fluid samples. A high prevalence of CWD-PrPSc was found in samples collected at the late-presymptomatic stage of the disease. Our results showed a correlation between the presence of CWD-PrPSc in male reproductive organs and blood. These findings demonstrate a high efficiency of CWD prion detection by PMCA in testes, epididymis and seminal fluid, and offer a possibility for a routine screening of semen samples to be commercially distributed for artificial insemination. Our results may uncover new opportunities to understand the mechanisms of CWD spreading and decrease putative inter-individual transmission associated to insemination using CWD contaminated specimens.


PLoS One. 2019; 14(12): e0226560. Published online 2019 Dec 30. doi: 10.1371/journal.pone.0226560

PMCID: PMC6936793PMID: 31887141

In Vitro detection of Chronic Wasting Disease (CWD) prions in semen and reproductive tissues of white tailed deer bucks (Odocoileus virginianus)

Our findings reveal the presence of CWD prions in semen and sexual tissues of prion infected WTD bucks. Future studies will be necessary to determine whether sexual contact and/or artificial inseminations are plausible means of CWD transmission in susceptible animal species.


Very low oral exposure to prions of brain or saliva origin can transmit chronic wasting disease

We report that oral exposure to as little as 300 nanograms (ng) of CWD-positive brain or to saliva containing seeding activity equivalent to 300 ng of CWD-positive brain, were sufficient to transmit CWD disease. This was true whether the inoculum was administered as a single bolus or divided as three weekly 100 ng exposures. However, when the 300 ng total dose was apportioned as 10, 30 ng doses delivered over 12 weeks, no infection occurred. While low-dose exposures to prions of brain or saliva origin prolonged the time from inoculation to first detection of infection, once infection was established, we observed no differences in disease pathogenesis. These studies suggest that the CWD minimum infectious dose approximates 100 to 300 ng CWD-positive brain (or saliva equivalent), and that CWD infection appears to conform more with a threshold than a cumulative dose dynamic.


Study raises possibility of sexual spread of CWD in deer

Stephanie Soucheray | News Reporter | CIDRAP News January 17, 2020 Chronic Wasting Disease


TUESDAY, JUNE 27, 2023

USAHA Report of the Subcommittee on Farmed Cervidae CWD TSE Prion Herds 2015 to 2023


SUNDAY, FEBRUARY 16, 2020

***> Jerking for Dollars, Are Texas Politicians and Legislators Masturbating Deer For Money, and likely spreading CWD TSE Prion?


Proposed Amendments to Disease Management and Response Regulations Chronic Wasting Disease CWD TSE Prion Singeltary Updated Submission October 20, 2023


TUESDAY, DECEMBER 31, 2019

In Vitro detection of Chronic Wasting Disease (CWD) prions in semen and reproductive tissues of white tailed deer bucks (Odocoileus virginianus


WEDNESDAY, MARCH 13, 2019

CWD, TSE, PRION, MATERNAL mother to offspring, testes, epididymis, seminal fluid, and blood


TUESDAY, DECEMBER 31, 2019

In Vitro detection of Chronic Wasting Disease (CWD) prions in semen and reproductive tissues of white tailed deer bucks (Odocoileus virginianus


WEDNESDAY, MARCH 13, 2019

CWD, TSE, PRION, MATERNAL mother to offspring, testes, epididymis, seminal fluid, and blood


***> Chronic Wasting Disease CWD TSE Prion Poker and Politics, are you all in $$$

Powerful Abbott appointee's lobbying sparks blowback in Legislature

In an ironic twist for Gov. Greg Abbott, who has made ethics reform an urgent political priority, the Texas House is taking aim at what critics call a "pay to play" culture among his appointees.

Powerful Abbott appointee's lobbying sparks blowback in Legislature In an ironic twist for Gov. Greg Abbott, who has made ethics reform an urgent political priority, the Texas House is taking aim at what critics call a "pay to play" culture among his appointees.

BY JAY ROOT MAY 12, 2017 12 AM CENTRAL


Jerking for Dollars, and CWD TSE Prion, what if?

Talk about big bucks: Deer semen donations are fueling South Texas campaign Each deer semen straw — from bucks with names like Gladiator Sunset, Sweet Dreams and Bandit — was assigned a $1,000 value, according to her campaign finance report.

Talk about big bucks: Deer semen donations are fueling South Texas campaign Each deer semen straw — from bucks with names like Gladiator Sunset, Sweet Dreams and Bandit — was assigned a $1,000 value, according to her campaign finance report.

AUSTIN — Donations of deer semen, one of Texas deer breeders’ most precious commodities, account for more than half of the contributions to a South Texan’s state House campaign.

Snip…

Each deer semen straw — from bucks with names like Gladiator Sunset, Sweet Dreams and Bandit — was assigned a $1,000 value, according to her campaign finance report.

A straw refers to the container of ejaculate that is stored for later use. Breeders market their deers’ antler size and shape as reasons to buy straws from their bucks. Uvalde deer breeder Fred Gonzalez said the donors’ straws went into a semen tank to be sold as one lot at a Texas Deer Association event last month and donated to her campaign.

Gonzalez, the treasurer of the Texas Deer Association, donated one straw to the lot. He said the deer breeding community often donates straws instead of money, although not usually directly to a political campaign.

“Semen is a very common way for us to donate,” he said. “One collection on a buck could lead to 60 straws sometimes. If you have a desirable animal, it’s a way to bring value without breaking the bank.”

The Texas Deer Association’s political action committee has received $976,025 in deer semen donations between 2006 and 2016. It has given $885,695 to campaigns and interest groups in the same span. According to expenditure reports between 2006 and 2016, the PAC has never given in-kind donations in the form of deer semen. Though the straws donated to Garza were sold at a Texas Deer Association event, the organization’s political action committee did not contribute to her campaign

Texas Deer Association contributions

The association’s political action committee has contributed $885,695 to campaigns and interest groups between 2006 and 2016. These are the top 10 candidates who have received money.

Candidate Amount

Rep. Ernest Bailes (R) $45,000

Rep. Lyle Larson (R) $26,611

Rep. Lance Gooden (R) $21,250

House Speaker Joe Straus (R) $21,000

Lt. Gov. Dan Patrick (R) $20,000

Comptroller Glenn Hegar (R) $16,000

Sen. Juan Hinojosa (D) $13,500

Rep. Todd Hunter (R) $13,000

Rep. Ryan Guillen (D) $12,750

Sen. Craig Estes (R) $12,500

SOURCE: Texas Ethics Commission


Deer semen donations among campaign contributions to South Texas candidate

Donations were made as part of an auction event

By Andrea Zelinski Published 1:26 pm CST, Wednesday, February 28, 2018

A South Texas candidate for the state House reported $51,000 worth of campaign contributions in deer semen, according to campaign finance reports.

AUSTIN — Many political candidates accept political gifts like food for events or legal advice for their campaigns, but one candidate from South Texas reported receiving thousands of dollars worth of deer semen.

Ana Lisa Garza, a district court judge in Starr County, reported accepting at least 40 semen straws, doses valued at $51,000. According to a report filed with the Texas Ethics Commission, several of the in-kind donations were made as part of a Feb. 10 auction event.

Although deer have been bred for over a century, interest has spiked in recent decades, in part due to interest in a buck named Patrick that was kept as a pet in the Midwest and grew large and unique antlers in the 1980s.

The practice has since grown into a budding industry in Texas. The deer, with their attractive racks, are now largely used for hunting, venison or further breeding.

In the filings, the straws are largely named after their sperm donors, including "Mabo Thicket" "Tack Hammer," "Strike Force." Other names of the straws include, "Bambi Chewy."

The economic impact of the deer breeding industry is $349.4 million annually in the state, according to a 2017 study by Texas A&M University. Combined with hunting, the study valued the industry's economic impact at $1.6 billion annually, according to the report.

The Texas Deer Association did not respond to requests for comment.


FRIDAY, JANUARY 27, 2017

TEXAS, Politicians, TAHC, TPWD, and the spread of CWD TSE Prion in Texas


SUNDAY, JANUARY 22, 2017

Texas 85th Legislative Session 2017 Chronic Wasting Disease CWD TSE Prion Cervid Captive Breeder Industry


SUNDAY, MAY 14, 2017

85th Legislative Session 2017 AND THE TEXAS TWO STEP Chronic Wasting Disease CWD TSE Prion, and paying to play $$$


TUESDAY, AUGUST 02, 2016

TEXAS TPWD Sets Public Hearings on Deer Movement Rule Proposals in Areas with CWD Rule Terry S. Singeltary Sr. comment submission


SUNDAY, MAY 22, 2016

TEXAS CWD DEER BREEDERS PLEA TO GOVERNOR ABBOTT TO CIRCUMVENT TPWD SOUND SCIENCE TO LET DISEASE SPREAD


Wednesday, May 04, 2016

TPWD proposes the repeal of §§65.90 -65.94 and new §§65.90 -65.99 Concerning Chronic Wasting Disease - Movement of Deer Singeltary Comment Submission


SUNDAY, AUGUST 02, 2015

TEXAS CWD, Have you been ThunderStruck, deer semen, straw bred bucks, super ovulation, and the potential TSE Prion connection, what if?


TUESDAY, DECEMBER 16, 2014

Texas 84th Legislature 2015 H.R. No. 2597 Kuempel Deer Breeding Industry TAHC TPWD CWD TSE PRION


Texas 84th Legislative Session Sunday, December 14, 2014

*** TEXAS 84th Legislature commencing this January, deer breeders are expected to advocate for bills that will seek to further deregulate their industry


***> TEXAS HISTORY OF CWD <***

Singeltary telling TAHC, that CWD was waltzing into Texas from WSMR around Trans Pecos region, starting around 2001, 2002, and every year, there after, until New Mexico finally shamed TAHC et al to test where i had been telling them to test for a decade. 2012 cwd was detected first right there where i had been trying to tell TAHC for 10 years.

***> Singeltary on Texas Chronic Wasting Disease CWD TSE Prion History <***


PITUITARY EXTRACT This was used to help cows super ovulate. This tissue was considered to be of greatest risk of containing BSE and consequently transmitting the disease...

supercalifragilisticexpialidocious or superovulationcwdtsepriondocious ?

Superovulation and embryo recovery in Red deer (Cervus elaphus ) hinds.

Fennessy PF1, Fisher MW, Shackell GH, Mackintosh CG. Author information 1Invermay Agricultural Centre Private Bag Mosgiel New Zealand.

Abstract

In two experiments, Red deer hinds were synchronized with intravaginal progesterone and were given 4 d of treatment (3 d before progesterone withdrawal and 1 d after) with an ovine follicle stimulating hormone (FSH) preparation which had a claimed low level of luteinizing hormone (LH) contamination. In Experiment 1, 12 hinds received one of four FSH levels by osmotic minipump. Hinds were run with fertile stags, and laparotomy and embryo recovery were performed 9 d after progesterone withdrawal. The ovulation rates (mean of three hinds per dosage) were 1.0, 2.0, 4.3 and 15.3 (number of corpora lutea counted) for estimated daily dosages rates of 0.036, 0.071, 0.11 and 0.14 units FSH preparation/day; the response to the increasing dosage was exponential (P<0.01). The recovery rate of ova on flushing was 38% (24 63 ), with all recovered ova being fertilized and of transferable quality. In Experiment 2, performed later in the breeding season, eight hinds received 0.14 units FSH/day either by minipump or by intramuscular injection. The mean ovulation rates were 3.0 and 11.0 (a significant difference, P<0.01), respectively, with a recovery rate of 72% (34 47 ), and with only 18 34 ova considered to be of transferable quality. The recovery rate in Experiment 2 was significantly higher than that in Experiment 1 (P<0.001). Overall, the results were better than those previously recorded for red deer, perhaps a function of both the FSH preparation used and an improved progesterone profile in estrus synchronization.


>> ovine follicle stimulating hormone (FSH) F8174 Sigma Follicle Stimulating Hormone from sheep pituitary Synonym: FSH


Louping-ill vaccine sheep scrapie blunder Vaccine for issue had to be free from detectable, living virus and capable of protecting sheep against a test dose of virus applied subcutaneously. The 1935 vaccine conformed to these standards and was issued for inoculation in March as three separate batches labelled 1, 2, and 3. The tissues of 140 sheep were employed to make batch 1 of which 22,270 doses were used; 114 to make batch 2 of which 18,000 doses were used and 44 to make batch 3 of which 4,360 doses were used. All the sheep tissues incorporated in the vaccine were obtained from yearling sheep. During 1935 and 1936 the vaccine proved highly efficient in the prevention of loup-ill and no user observed an ill-effect in the inoculated animals. In September, 1937, two and a half years after vaccinating the sheep, two owners complained that scrapie, a disease which had not before been observed in the Blackface breed, was appearing in their stock of Blackface sheep and further that it was confined to animals vaccinated with louping-ill vaccine in 1935. At that stage it was difficult to conceive that the occurrence could be associated with the injection of the vaccine but in view of the implications, I visited most of the farms on which sheep had been vaccinated in 1935. It was at this point that the investigation reached its dramatic phase; I shall not forget the profound effect on my emotions when I visited these farms and was warmly welcomed because of the great benefits resulting from the application of louping-ill vaccine, wheras the chief purpose of my visit was to determine if scrapie was appearing in the inoculated sheep. The enquiry made the position clear. Scrapie was developing in the sheep vaccinated in 1935 and it was only in a few instances that the owner was associating the occurrence with louping-ill vaccination. The disease was affecting all breeds and it was confined to the animals vaccinated with batch 2. This was clearly demonstrated on a number of farms on which batch 1 had been used to inoculate the hoggs in 1935 and batch 2 to inoculate the ewes. None of the hoggs, which at this time were three- year-old ewes. At this time it was difficult to forecast whether all of the 18,000 sheep which had received batch 2 vaccine would develop scrapie. It was fortunate, however, that the majority of the sheep vaccinated with batch 2 were ewes and therfore all that were four years old and upwards at the time of vaccination had already been disposed of and there only remained the ewes which had been two to three years old at the time of vaccination, consequently no accurate assessment of the incidence of scrapie could be made. On a few farms, however, where vaccination was confined to hoggs, the incidence ranged from 1 percent, to 35 percent, with an average of about 5 percent. Since batch 2 vaccine had been incriminated as a probable source of scrapie infection, an attempt was made to trace the origin of the 112 sheep whose tissues had been included in the vaccine. It was found that they had been supplied by three owners and that all were of the Blackface or Greyface breed with the exception of eight which were Cheviot lambs born in 1935 from ewes which had been in contact with scrapie infection. Some of these contact ewes developed scrapie in 1936-37 and three surviving fellow lambs to the eight included in the batch 2 vaccine of 1935 developed scrapie, one in September, 1936, one in February, 1937, and one in November, 1937. There was, therefore, strong presumptive evidence that the eight Cheviot lambs included in the vaccine althought apparently healthy were, in fact, in the incubative stage of a scrapie infection and that in their tissues there was an infective agent which had contaminated the batch 2 vaccine, rendering it liable to set up scrapie. If that assumption was correct then the evidence indicated that:-

(1) the infective agent of scrapie was present in the brain, spinal cord and or spleen of infected sheep:

(2) it could withstand a concentration of formalin of 0-35 percent, which inactivated the virus of louping-ill:

(3) it could be transmitted by subcutaneous inoculation;

(4) it had an incubative period of two years and longer.

http://www.fda.gov/ohrms/dockets/ac/01/slides/3681s2_09.pdf 

See archived link;


see part of old report I received;


see vaccines;


(It was noted with concern that hormone extracts could be manufactured by a veterinary surgeon for administration to animals under his care without any Medicines Act Control.) PITUITARY EXTRACT This was used to help cows super ovulate.

*** This tissue was considered to be of greatest risk of containing BSE and consequently transmitting the disease.

*** BEEF BRAIN AND BRAIN INFUSION BROTHS Considered to be of great risk.



THURSDAY, JULY 10, 2014

supercalifragilisticexpialidocious or superovulationcwdtsepriondocious ?


2025

Failure to prevent classical scrapie after repeated decontamination of a barn

Published: 25 March 2025

Timm Konold, John Spiropoulos, Peter Bellerby & Hugh A Simmons BMC Research Notes volume 18, Article number: 126 (2025) Cite this article

Prions, the causative agent of scrapie in sheep, are extremely resistant to disinfection and can remain biologically active for years, which makes it challenging to prevent re-infection of susceptible animals on farms after a scrapie outbreak. The present study investigated the effectiveness of disinfection of a barn that previously housed scrapie-affected sheep as part of the husbandry of scrapie infected sheep on the farm. The barn was decontaminated with sodium hypochlorite for four times the recommended exposure time. Two cohorts, consisting of 25 and 21 sheep, with susceptible prion protein genotypes (VRQ/VRQ), born 2 years apart, were housed in the barn and infection monitored by examination of rectal biopsies.

Results

One sheep from the first cohort and four from the second were found to be infected from 775 (first cohort) and 550 days (second cohort) post exposure. It is concluded that decontamination with sodium hypochlorite at the recommended concentration and longer exposure time did not prevent re-infection of susceptible sheep. Disinfection of contaminated premises to eradicate scrapie continues to be a challenge.

Snip…

Discussion

Cleaning and disinfection (C&D) are imperative in any animal disease outbreak to reduce contamination and prevent re-infection of animals newly introduced animals. Unfortunately, the infectious agent responsible for TSEs, including scrapie, is extremely resistant to disinfection and other inactivation protocols and can persist in the environment for many years, which makes this very challenging [1]. Validated disinfection protocols based on experimental settings commonly applied use either sodium hydroxide or sodium hypochlorite, which are extremely corrosive, hazardous to humans and animals, and its use in a farm setting is questionable. Indeed, previous studies utilising the same farm as the one used in the current study have shown that effective decontamination of an animal barn that housed scrapie-affected sheep is virtually impossible because infection still re-occurs [2, 4]. It was hypothesized that the most likely cause of re-infection was dust from contaminated surroundings because of the detection of prions in dust samples collected in the barn [4]. However, a study assessing infectivity of field furniture suggested that there may be gradual reduction of prion activity through the weathering process (repeated cycle of environmental heat and cold) [9]. If this was the case, it should be possible to achieve sufficient decontamination over time if the disinfection protocol in the barn was continued. The current study aimed to assess whether inactivation may be possible over time by repeated decontamination using longer exposure times than recommended (4 × 1 h rather than a single hour [1]).

It was acknowledged that it may be difficult to assess contamination at very low levels by bioassay because sample size needs to increase. Twenty-five sheep used in the 2016-born cohort would have been sufficient to detect an infection rate of about 11% with 95% confidence. It was unfortunate that infection of a single sheep was only detected at 775 dpe, by which time we had already moved a second group into the barn. Retrospectively, it might have been better to wait until all sheep in the 2016-born had been culled and examined to determine scrapie status and then decide on the future, e.g. another cycle of C&D with introduction of sheep or discontinue, but it would not have taken into account that results may differ between groups at different time points when contamination may increase (due to more dust) or decrease (due to more inactivation of prions from the outside because of the weathering process). There appeared to be an increase in infection rate although the difference between the 2016- and 2018-born cohort was not significant. It is possible that this was a result of gradual increase in contamination, caused by the single scrapie-positive sheep at 775 dpe in the 2016-born cohort, by the scrapie-positive sheep in the 2018-cohort and resulting contamination of the whole barn, by dust from the outside, by dust from the ceiling that was not disinfected or by a combination of these. The first positive animal in the 2018-born cohort was detected by rectal biopsy examination at 550 dpe, which was 358 days after the previous, negative biopsy and considerably earlier than in the 2016-born cohort (775 dpe), which may imply a higher level of prion contamination of the barn. It has been shown that in natural infection prions can be detected by immunohistochemistry in lymphoid tissue in VRQ/VRQ lambs from 2 months of age [10, 11] and may be detected in the enteric nervous system of the small intestine up to 9 months before being detected in rectal tissue [12]. As shedding of the infectious agent from infected sheep may occur very early after infection, particularly in VRQ/VRQ sheep with an extensive lymphoid prion spread, it is likely that infected animals contributed to the subsequent infection of other sheep in the pen or spread of prions in dust prior to their removal from the barn. However, it would not explain the infection of the single sheep in the 2016-born cohort, which was by prions from the outside or by prions within the barn that were not inactivated during the disinfection process. Nevertheless, there was a significant reduction in infection incidence compared to the previous study with the same decontamination regime, which caused infection of 24 or 25 sheep [4], even though complete inactivation of prions was not achieved.

The comparatively long period between exposure and first detection of PrPSc in RAMALT (775 days) and low infection rate (1 of 25) in the 2016-born cohort is suggestive of low infectious titre contamination with the scrapie agent. In 2002, six of eight lambs exposed to pasture on this farm from 2 days of age for 12 months without contact to scrapie-affected sheep had a median survival time of 794 days [13], i.e. they were at or close to clinical end-stage by the time the sheep in the 2016 cohort was just confirmed to be infected. The data from the 2018-born cohort suggest that it may take a minimum of 358 days from the day of first detection of PrPSc in RAMALT to clinical end-stage. Exposure of VRQ heterozygous sheep or sheep without a VRQ allele may result in an even longer incubation period, and infection may go unnoticed for some time leading to the erroneous assumption that sheep are free from the disease. As scrapie surveillance is generally restricted to examination of brain only, sheep at an earlier stage of infection when PrPSc spread to the central nervous system has not yet occurred may be missed.

In conclusion, this study has shown that repeated disinfection with sodium hypochlorite, even using extended decontamination times, did not prevent re-infection so that there is a risk of re-infection if sheep with susceptible genotypes are re-introduced. It is not known whether decontamination was ineffective or recontamination occurred from various sources.

Limitations

Source of contamination could not be established, which would potentially help to suggest prevention strategies.

Study design was not ideal due to the unpredictable nature of prion diseases (long incubation period until detection of infection in the first cohort but unexpectedly shorter in the second cohort).


Rapid recontamination of a farm building occurs after attempted prion removal

First published: 19 January 2019 https://doi.org/10.1136/vr.105054

The data illustrates the difficulty in decontaminating farm buildings from scrapie, and demonstrates the likely contribution of farm dust to the recontamination of these environments to levels that are capable of causing disease.

snip...

This study clearly demonstrates the difficulty in removing scrapie infectivity from the farm environment. Practical and effective prion decontamination methods are still urgently required for decontamination of scrapie infectivity from farms that have had cases of scrapie and this is particularly relevant for scrapie positive goatherds, which currently have limited genetic resistance to scrapie within commercial breeds.24 This is very likely to have parallels with control efforts for CWD in cervids.


***>This is very likely to have parallels with control efforts for CWD in cervids.


Front. Vet. Sci., 14 September 2015 | https://doi.org/10.3389/fvets.2015.00032

Objects in contact with classical scrapie sheep act as a reservoir for scrapie transmission

In conclusion, the results in the current study indicate that removal of furniture that had been in contact with scrapie-infected animals should be recommended, particularly since cleaning and decontamination may not effectively remove scrapie infectivity (31), even though infectivity declines considerably if the pasture and the field furniture have not been in contact with scrapie-infected sheep for several months. As sPMCA failed to detect PrPSc in furniture that was subjected to weathering, even though exposure led to infection in sheep, this method may not always be reliable in predicting the risk of scrapie infection through environmental contamination.


"Additionally, we have determined that prion seeding activity is retained for at least fifteen years at a contaminated site following attempted remediation."

15 YEARS!

Detection of prions in soils contaminated by multiple routes

Results: We are able to detect prion seeding activity at multiple types of environmental hotspots, including carcass sites, contaminated captive facilities, and scrapes (i.e. urine and saliva). Differences in relative prion concentration vary depending on the nature and source of the contamination. Additionally, we have determined that prion seeding activity is retained for at least fifteen years at a contaminated site following attempted remediation.

Conclusions: Detection of prions in the environment is of the utmost importance for controlling chronic wasting disease spread. Here, we have demonstrated a viable method for detection of prions in complex environmental matrices. However, it is quite likely that this method underestimates the total infectious prion load in a contaminated sample, due to incomplete recovery of infectious prions. Further refinements are necessary for accurate quantification of prions in such samples, and to account for the intrinsic heterogeneities found in the broader environment.

Funded by: Wisconsin Department of Natural Resources

Prion 2023 Abstracts


Artificial mineral sites that pre-date endemic chronic wasting disease become prion hotspots

The detection of PrPCWD in soils at attractant sites within an endemic CWD zone significantly advances our understanding of environmental PrPCWD accumulation dynamics, providing valuable information for advancing adaptive CWD management approaches.


Detection of chronic wasting disease prions in the farm soil of the Republic of Korea

Here, we show that prion seeding activity was detected in extracts from farm soil following 4 years of incubation with CWD-infected brain homogenate.


***> Infectious agent of sheep scrapie may persist in the environment for at least 16 years

***> Nine of these recurrences occurred 14–21 years after culling, apparently as the result of environmental contamination, but outside entry could not always be absolutely excluded.

JOURNAL OF GENERAL VIROLOGY Volume 87, Issue 12

Infectious agent of sheep scrapie may persist in the environment for at least 16 years Free


In summary, CWD prions are efficiently transmitted to WTD via aerosolization using a delivered dose substantially lower than previously reported by the oral route. Our results provide further evidence that prions delivered to the nasal passages are sufficient to transmit CWD and allow the inference that aerosolization may facilitate the transmission of prions in general.


In summary, our results establish aerosols as a surprisingly efficient modality of prion transmission. This novel pathway of prion transmission is not only conceptually relevant for the field of prion research, but also highlights a hitherto unappreciated risk factor for laboratory personnel and personnel of the meat processing industry. In the light of these findings, it may be appropriate to revise current prion-related biosafety guidelines and health standards in diagnostic and scientific laboratories being potentially confronted with prion infected materials. While we did not investigate whether production of prion aerosols in nature suffices to cause horizontal prion transmission, the finding of prions in biological fluids such as saliva, urine and blood suggests that it may be worth testing this possibility in future studies.


Published: 25 March 2025

Failure to prevent classical scrapie after repeated decontamination of a barn

Timm Konold, John Spiropoulos, Peter Bellerby & Hugh A Simmons BMC Research Notes volume 18, Article number: 126 (2025) Cite this article

In conclusion, this study has shown that repeated disinfection with sodium hypochlorite, even using extended decontamination times, did not prevent re-infection so that there is a risk of re-infection if sheep with susceptible genotypes are re-introduced. It is not known whether decontamination was ineffective or recontamination occurred from various sources.


SUNDAY, APRIL 06, 2025

Failure to prevent classical scrapie after repeated decontamination of a barn



***> Trucking CWD <***


Chronic wasting disease detection in environmental and biological samples from a taxidermy site

Paulina Sotoa,b, J. Hunter Reedc, Mitch Lockwoodc, and Rodrigo Moralesa,b aDepartment of Neurology, McGovern Medical School, University of Texas Health Science Center at Houston, Texas, USA; bUniversidad Bernardo O’Higgins, Santiago, Chile; cTexas Parks and Wildlife Department, Texas, USA

Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy affecting captive and free-ranging cervids (e.g., mule deer, white-tailed deer, elk, reindeer, and moose). Nowadays, CWD is widely distributed in North America. It is suggested that CWD spreads due to direct animal contact or through exposure to contaminated environments previously inhabited by infected animals. CWD may also be spread through the movement of infected animals and carcasses. Taxidermy practices involve processing deer tissues (or whole animal carcasses). In many cases, the CWD status of processed animals is unknown. This can generate risks of disease spread and transmission. Taxidermy practices include different steps involving physical, chemical, and biological procedures. Without proper tissue handling or disposal practices, taxidermist facilities may become a focus of prion infectivity. Aims: In this study, we evaluated the presence of infectious prions in a taxidermy facility believed to be exposed to CWD. Detection was performed using the Protein Misfolding Cyclic Amplification (PMCA) technique in biological and inert environmental samples.

Methods: We collected biological and environmental samples (plants, soils, insects, excreta, and others) from a taxidermy facility, and we tested these samples using the PMCA technique. In addition, we swabbed different surfaces possibly exposed to CWD-infected animals. For the PMCA reaction, we directly used a swab piece or 10 µL of 20% w/v homogenized samples.

Results: The PMCA analysis demonstrated CWD seeding activity in some of the components of this facility, including insects involved in head processing, soils, and a trash dumpster.

Conclusions: Different areas of this property were used for various taxidermy procedures. We were able to detect the presence of prions in i) soils that were in contact with the heads of dead animals, ii) insects involved in the cleaning of skulls, and iii) an empty dumpster where animal carcasses were previously placed. This is the first report demonstrating that swabbing is a helpful method to screen for prion infectivity on surfaces potentially contaminated with CWD. These findings are relevant as this swabbing and amplification strategy may be used to evaluate the disease status of other free-ranging and captive settings where there is a concern for CWD transmissions, such as at feeders and water troughs with CWD-exposed properties. This approach could have substantial implications for free-ranging cervid surveillance as well as in epidemiological investigations of CWD.

Funded by: USDA

Grant number: AP20VSSPRS00C143

Prion 2022 Conference abstracts: pushing the boundaries


Chronic Wasting Disease Carcass Disposal Dumpster Management and Biosecurity

BACKGROUND INFORMATION:

State and tribal wildlife agencies may identify collection points (dumpsters) within an identified chronic wasting disease (CWD) management zone for the disposal of hunter-harvested cervid carcasses to remove potentially infected carcasses off the landscape for disposal by an approved method (Gillin & Mawdsley, 2018, chap.14). However, depending on their placement and maintenance these dumpsters could potentially increase the risk of CWD transmission.

In several different states, photographic evidence has shown dumpsters in state identified CWD management zones overflowing with deer carcasses and limbs scattered on the land nearby. This could provide an opportunity for scavengers to potentially move infected carcass material to non-infected zones or increase contamination of the ground material around the dumpster’s location.

Federal guidance does not explicitly address uniform standards for collection locations for carcasses of free-ranging cervids; however, the United States Department of Agriculture, Animal and Plant Health Inspection Service, Veterinary Services Program Standards on CWD outlines procedures for carcass disposal, equipment sanitation, and decontamination of premises for captive cervid facilities.

RESOLUTION:

The United States Animal Health Association urges the Association of Fish and Wildlife Agencies (AFWA), Wildlife Health Committee to further refine the AFWA Technical Report on Best Management Practices for Prevention, Surveillance, and Management of Chronic Wasting Disease; Chapter 14, Carcass Disposal to address the placement and management of chronic wasting disease carcass disposal dumpsters or other carcass collection containers.

Reference:

1. Gillin, Colin M., and Mawdsley, Jonathan R. (eds.). 2018. AFWA Technical Report on Best Management Practices for Surveillance, Management and Control of Chronic Wasting Disease. Association of Fish and Wildlife Agencies, Washington, D. C. 111 pp.


THE CWD TSE Prion aka mad cow type disease is not your normal pathogen.

The TSE prion disease survives ashing to 600 degrees celsius, that’s around 1112 degrees farenheit.

YOU cannot cook the TSE prion disease out of meat.

YOU can take the ash and mix it with saline and inject that ash into a mouse, and the mouse will go down with TSE.

Prion Infected Meat-and-Bone Meal Is Still Infectious after Biodiesel Production as well.

The TSE prion agent also survives Simulated Wastewater Treatment Processes.

IN fact, you should also know that the TSE Prion agent will survive in the environment for years, if not decades.

YOU can bury it and it will not go away.

The TSE agent is capable of infected your water table i.e. Detection of protease-resistant cervid prion protein in water from a CWD-endemic area.

it’s NOT your ordinary pathogen you can just cook it out and be done

New studies on the heat resistance of hamster-adapted scrapie agent: Threshold survival after ashing at 600°C suggests an inorganic template of replication


Prion Infected Meat-and-Bone Meal Is Still Infectious after Biodiesel Production


March 13, 2025

Prion Partitioning and Persistence in Environmental Waters


Prions in Waterways


Detection of protease-resistant cervid prion protein in water from a CWD-endemic area


A Quantitative Assessment of the Amount of Prion Diverted to Category 1 Materials and Wastewater During Processing


Rapid assessment of bovine spongiform encephalopathy prion inactivation by heat treatment in yellow grease produced in the industrial manufacturing process of meat and bone meals


THURSDAY, FEBRUARY 28, 2019

BSE infectivity survives burial for five years with only limited spread


2001, I remember what someone told me ‘In Confidence’, about Scrapie, I never forgot, and it seems it’s come to pass;

***> Confidential!!!!

***> As early as 1992-3 there had been long studies conducted on small pastures containing scrapie infected sheep at the sheep research station associated with the Neuropathogenesis Unit in Edinburgh, Scotland. Whether these are documented...I don't know. But personal recounts both heard and recorded in a daily journal indicate that leaving the pastures free and replacing the topsoil completely at least 2 feet of thickness each year for SEVEN years....and then when very clean (proven scrapie free) sheep were placed on these small pastures.... the new sheep also broke out with scrapie and passed it to offspring. I am not sure that TSE contaminated ground could ever be free of the agent!! A very frightening revelation!!!

---end personal email---end...tss

and so it seems…so, this is what we leave our children and grandchildren?

Aug 18, 2021

Oh, Deer

Heading Off a Wildlife Epidemic

CWD poses a significant threat to the future of hunting in Texas. Deer population declines of 45 and 50 percent have been documented in Colorado and Wyoming. A broad infection of Texas deer populations resulting in similar population impacts would inflict severe economic damage to rural communities and could negatively impact land markets. Specifically, those landowners seeking to establish a thriving herd of deer could avoid buying in areas with confirmed CWD infections. As they do with anthrax-susceptible properties, land brokers may find it advisable to inquire about the status of CWD infections on properties that they present for sale. Prospective buyers should also investigate the status of the wildlife on prospective properties. In addition, existing landowners should monitor developments as TPWD crafts management strategies to identify and contain this deadly disease.

Dr. Gilliland (c-gilliland@tamu.edu) is a research economist with the Texas Real Estate Research Center at Texas A&M University.


Texas CWD Surveillance Positives Tracking Page is outdated


My last figures of Texas CWD Totals To Date were 1061 Confirmed, but that is way outdated.

Texas CWD total by calendar years


Counties where CWD Exposed Deer were Released


Number of CWD Exposed Deer Released by County


CWD Status Captive Herds


Texas Game Wardens Bust Illegal Deer Operations Across the State

Feb. 27, 2025

Media Contact: TPWD News, Business Hours, 512-389-8030

AUSTIN – A recent investigation by Texas Game Wardens resulted in approximately 1,200 pending charges and 22 suspects from across the state involved in the deer breeding industry and black-market wildlife trade.

The suspects and charges are associated with three deer breeding facilities, ten release sites, one deer management pen and three illegal facilities not registered in the Texas Wildlife Information Management Services (TWIMS) database, meaning they were operating or receiving deer in violation of registration requirements and disease monitoring protocols.



What next, pigs, cattle, and sheep, humans, oral transmission, oh my!

Detection of Prions in Wild Pigs (Sus scrofa) from Areas with Reported Chronic Wasting Disease Cases, United States

Volume 31, Number 1—January 2025

Abstract

Using a prion amplification assay, we identified prions in tissues from wild pigs (Sus scrofa) living in areas of the United States with variable chronic wasting disease (CWD) epidemiology. Our findings indicate that scavenging swine could play a role in disseminating CWD and could therefore influence its epidemiology, geographic distribution, and interspecies spread.

Snip…

Conclusions

In summary, results from this study showed that wild pigs are exposed to cervid prions, although the pigs seem to display some resistance to infection via natural exposure. Future studies should address the susceptibility of this invasive animal species to the multiple prion strains circulating in the environment. Nonetheless, identification of CWD prions in wild pig tissues indicated the potential for pigs to move prions across the landscape, which may, in turn, influence the epidemiology and geographic spread of CWD.


Discussion

snip...

In the case of feral pigs, exposure to the agent of CWD through scavenging of CWD-affected cervid carcasses or through consumption of prion contaminated plants or soil could allow feral pigs to serve as reservoirs of CWD infectivity. The range and numbers of feral pigs is predicted to continue to increase due to the ability of pigs to adapt to many climates, reproduce year-round, and survive on a varied diet (55 ). The range of CWD-affected cervids also continues to spread, increasing the likelihood of overlap of ranges of feral pigs and CWD -affected environments.

We demonstrate here that PrPSc accumulates in lymphoid tissues from pigs inoculated intracranially or orally with the CWD agent, and can be detected as early as 6 months after inoculation. Clinical disease suggestive of prion disease developed only in a single pig after a long (64 months) incubation period. This raises the possibility that CWD-infected pigs could shed prions into their environment long before they develop clinical disease. However, the low amounts of PrPSc detected in the study pigs combined with the low attack rates in Tg002 mice suggest that there is a relatively strong species barrier to CWD prions in pigs.


Although the current U.S. feed ban is based on keeping tissues from TSE infected cattle from contaminating animal feed, swine rations in the U.S. could contain animal derived components including materials from scrapie infected sheep and goats. These results indicating the susceptibility of pigs to sheep scrapie, coupled with the limitations of the current feed ban, indicates that a revision of the feed ban may be necessary to protect swine production and potentially human health.

2. Determined that pigs naturally exposed to chronic wasting disease (CWD) may act as a reservoir of CWD infectivity. Chronic wasting disease is a naturally occurring, fatal, neurodegenerative disease of cervids. The potential for swine to serve as a host for the agent of CWD disease is unknown. The purpose of this study was to investigate the susceptibility of swine to the CWD agent following experimental oral or intracranial inoculation. Pigs were assigned to 1 of 3 groups: intracranially inoculated; orally inoculated; or non-inoculated. At market weight age, half of the pigs in each group were tested ('market weight' groups). The remaining pigs ('aged' groups) were allowed to incubate for up to 73 months post inoculation (MPI). Tissues collected at necropsy were examined for disease-associated prion protein (PrPSc) by multiple diagnostic methods. Brain samples from selected pigs were bioassayed in mice expressing porcine prion protein. Some pigs from each inoculated group were positive by one or more tests. Bioassay was positive in 4 out of 5 pigs assayed. Although only small amounts of PrPSc were detected using sensitive methods, this study demonstrates that pigs can serve as hosts for CWD. Detection of infectivity in orally inoculated pigs using mouse bioassay raises the possibility that naturally exposed pigs could act as a reservoir of CWD infectivity. Currently, swine rations in the U.S. could contain animal derived components including materials from deer or elk. In addition, feral swine could be exposed to infected carcasses in areas where CWD is present in wildlife populations. The current feed ban in the U.S. is based exclusively on keeping tissues from TSE infected cattle from entering animal feeds. These results indicating the susceptibility of pigs to CWD, coupled with the limitations of the current feed ban, indicates that a revision of the feed ban may be necessary to protect swine production and potentially human health.





Volume 31, Number 1—January 2025

Dispatch

Detection of Prions in Wild Pigs (Sus scrofa) from Areas with Reported Chronic Wasting Disease Cases, United States

Abstract

Using a prion amplification assay, we identified prions in tissues from wild pigs (Sus scrofa) living in areas of the United States with variable chronic wasting disease (CWD) epidemiology. Our findings indicate that scavenging swine could play a role in disseminating CWD and could therefore influence its epidemiology, geographic distribution, and interspecies spread.

Snip…

Conclusions In summary, results from this study showed that wild pigs are exposed to cervid prions, although the pigs seem to display some resistance to infection via natural exposure. Future studies should address the susceptibility of this invasive animal species to the multiple prion strains circulating in the environment. Nonetheless, identification of CWD prions in wild pig tissues indicated the potential for pigs to move prions across the landscape, which may, in turn, influence the epidemiology and geographic spread of CWD.


***> Price of TSE Prion Poker goes up substantially, all you cattle ranchers and such, better pay close attention here...terry <***

Transmission of the chronic wasting disease agent from elk to cattle after oronasal exposure

Justin Greenlee, Jifeng Bian, Zoe Lambert, Alexis Frese, and Eric Cassmann Virus and Prion Research Unit, National Animal Disease Center, USDA-ARS, Ames, IA, USA

Aims: The purpose of this study was to determine the susceptibility of cattle to chronic wasting disease agent from elk.

Materials and Methods: Initial studies were conducted in bovinized mice using inoculum derived from elk with various genotypes at codon 132 (MM, LM, LL). Based upon attack rates, inoculum (10% w/v brain homogenate) from an LM132 elk was selected for transmission studies in cattle. At approximately 2 weeks of age, one wild type steer (EE211) and one steer with the E211K polymorphism (EK211) were fed 1 mL of brain homogenate in a quart of milk replacer while another 1 mL was instilled intranasally. The cattle were examined daily for clinical signs for the duration of the experiment. One steer is still under observation at 71 months post-inoculation (mpi).

Results: Inoculum derived from MM132 elk resulted in similar attack rates and incubation periods in mice expressing wild type or K211 bovine PRNP, 35% at 531 days post inoculation (dpi) and 27% at 448 dpi, respectively. Inoculum from LM132 elk had a slightly higher attack rates in mice: 45% (693 dpi) in wild type cattle PRNP and 33% (468) in K211 mice. Inoculum from LL132 elk resulted in the highest attack rate in wild type bovinized mice (53% at 625 dpi), but no K211 mice were affected at >700 days. At approximately 70 mpi, the EK211 genotype steer developed clinical signs suggestive of prion disease, depression, low head carriage, hypersalivation, and ataxia, and was necropsied. Enzyme immunoassay (IDEXX) was positive in brainstem (OD=4.00, but non-detect in retropharyngeal lymph nodes and palatine tonsil. Immunoreactivity was largely limited to the brainstem, midbrain, and cervical spinal cord with a pattern that was primarily glia-associated.

Conclusions: Cattle with the E211K polymorphism are susceptible to the CWD agent after oronasal exposure of 0.2 g of infectious material.

Funded by: This research was funded in its entirety by congressionally appropriated funds to the United States Department of Agriculture, Agricultural Research Service. The funders of the work did not influence study design, data collection and analysis, decision to publish, or preparation of the manuscript.

"Cattle with the E211K polymorphism are susceptible to the CWD agent after oronasal exposure of 0.2 g of infectious material."

=====end

Strain characterization of chronic wasting disease in bovine-PrP transgenic mice

Nuria Jerez-Garrido1, Sara Canoyra1, Natalia Fernández-Borges1, Alba Marín Moreno1, Sylvie L. Benestad2, Olivier Andreoletti3, Gordon Mitchell4, Aru Balachandran4, Juan María Torres1 and Juan Carlos Espinosa1. 1 Centro de Investigación en Sanidad Animal, CISA-INIA-CSIC, Madrid, Spain. 2 Norwegian Veterinary Institute, Ås, Norway. 3 UMR Institut National de la Recherche Agronomique (INRA)/École Nationale Vétérinaire de Toulouse (ENVT), Interactions Hôtes Agents Pathogènes, Toulouse, France. 4 Canadian Food Inspection Agency, Ottawa, Canada.

Aims: Chronic wasting disease (CWD) is an infectious prion disease that affects cervids. Various CWD prion strains have been identified in different cervid species from North America and Europe. The properties of the infectious prion strains are influenced by amino acid changes and polymorphisms in the PrP sequences of different cervid species. This study, aimed to assess the ability of a panel of CWD prion isolates from diverse cervid species from North America and Europe to infect bovine species, as well as to investigate the properties of the prion strains following the adaptation to the bovine-PrP context.

Materials and Methods: BoPrP-Tg110 mice overexpressing the bovine-PrP sequence were inoculated by intracranial route with a panel of CWD prion isolates from both North America (two white-tailed deer and two elk) and Europe (one reindeer, one moose and one red deer).

Results: Our results show distinct behaviours in the transmission of the CWD isolates to the BoPrP-Tg110 mouse model. Some of these isolates did not transmit even after the second passage. Those able to transmit displayed differences in terms of attack rate, survival times, biochemical properties of brain PrPres, and histopathology.

Conclusions: Altogether, these results exhibit the diversity of CWD strains present in the panel of CWD isolates and the ability of at least some CWD isolates to infect bovine species. Cattle being one of the most important farming species, this ability represents a potential threat to both animal and human health, and consequently deserves further study.

Funded by: MCIN/AEI /10.13039/501100011033 and by European Union NextGeneration EU/PRTR

Grant number: PCI2020-120680-2 ICRAD

"Altogether, these results exhibit the diversity of CWD strains present in the panel of CWD isolates and the ability of at least some CWD isolates to infect bovine species. Cattle being one of the most important farming species, this ability represents a potential threat to both animal and human health, and consequently deserves further study."

=====end


CWD Zoonosis Humans, what if?

CDC CWD TSE Prion Update 2025

KEY POINTS

Chronic wasting disease affects deer, elk and similar animals in the United States and a few other countries.

The disease hasn't been shown to infect people.

However, it might be a risk to people if they have contact with or eat meat from animals infected with CWD.


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. Nevertheless, we note that this study did not investigate the zoonotic potential of the Norway CWD prions. In North America, humans have historically consumed meat from CWD-infected animals, which has been documented to harbor prions (35,44–47). Despite the potential exposure to prions, no epidemiologic evidence indicates a correlation between the occurrence of CWD cases in animals and the prevalence of human prion diseases (48). A recent bioassay study reported no transmissions from 3 Nordic isolates into transgenic mice expressing human PrP (49). Therefore, our findings should be interpreted with caution in terms of human health implications, and further research is required to determine the zoonotic potential of these CWD strains.

The presence of prions in peripheral tissues indicates that CWD may have a systemic nature in all Norwegian cervid species, challenging the view that prions are exclusively localized in the CNS in sporadic CWD of moose and red deer. Our findings expand the notion of just how widely distributed prions can be in cervids affected with CWD and call into question the capability of emerging CWD strains in terms of infectivity to other species, including humans.

Appendix



Volume 31, Number 2—February 2025

Dispatch

Detection of Chronic Wasting Disease Prions in Raw, Processed, and Cooked Elk Meat, Texas, USA

Rebeca Benavente, Fraser Brydon, Francisca Bravo-Risi, Paulina Soto, J. Hunter Reed, Mitch Lockwood, Glenn Telling, Marcelo A. Barria, and Rodrigo MoralesComments to Author

Snip…

CWD prions have been detected in the muscle of both farmed and wild deer (10), and at concentrations relevant to sustain disease transmission (11). CWD prions have also been identified across several cervid species and in multiple tissues, including lymph nodes, spleen, tongue, intestines, adrenal gland, eyes, reproductive tissues, ears, lungs, and liver, among others (12–14). Those findings raise concerns about the safety of ingesting processed meats that contain tissues other than skeletal muscle (15) (Appendix). https://wwwnc.cdc.gov/eid/article/31/2/24-0906-app1.pdf .

In addition, those findings highlight the need for continued vigilance and research on the transmission risks of prion diseases and for development of new preventative and detection measures to ensure the safety of the human food supply.

Snip…

Overall, our study results confirm previous reports describing the presence of CWD prions in elk muscles (13). The data also demonstrated CWD prion persistence in food products even after processing through different procedures, including the addition of salts, spices, and other edible elements. 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.


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."


The detection and decontamination of chronic wasting disease prions during venison processing

Results: CWD prions were detected on all cutting boards (n= 3; replicates= 8/8, 8/8, 8/8 and knives (n= 3; replicates= 8/8, 8/8, 8/8) used in processing CWD-positive venison, but not on those used for CWD-negative venison. After processing CWD-positive venison, allowing the surfaces to dry, and washing the cutting board with Dawn dish soap, we detected CWD prions on the cutting board surface (n= 3; replicates= 8/8, 8/8, 8/8) but not on the knife (n= 3, replicates = 0/8, 0/8, 0/8). Similar patterns were observed with Briotech (cutting board: n= 3; replicates= 7/8, 1/8, 0/8; knife: n= 3; replicates = 0/8, 0/8, 0/8). We did not detect CWD prions on the knives or cutting boards after disinfecting with Virkon-S, 10% bleach, and 40% bleach.

Conclusions: These preliminary results suggest that Dawn dish soap and Briotech do not reliably decontaminate CWD prions from these surfaces. Our data suggest that Virkon-S and various bleach concentrations are more effective in reducing prion contamination of meat processing surfaces; however, surface type may also influence the ability of prions to adsorb to surfaces, preventing complete decontamination. Our results will directly inform best practices to prevent the introduction of CWD prions into the human food chain during venison processing.

Prion 2023 Abstracts


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.


Transmission of prion infectivity from CWD-infected macaque tissues to rodent models demonstrates the zoonotic potential of chronic wasting disease.

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

=====


Transmission of Cervid Prions to Humanized Mice Demonstrates the Zoonotic Potential of CWD

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 tg650with 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.


The finding that infectious PrPSc was shed in fecal material of CWD-infected humanized mice and induced clinical disease, different tropism, and typical three banding pattern-PrPres in bank voles that is transmissible upon second passage is highly concerning for public health. The fact that this biochemical signature in bank voles resembles that of the Wisc-1 original deer isolate and is different from that of bvWisc-1, in the migration profile and the glyco-form-ratio, is valid evidence that these results are not a product of contamination in our study. If CWD in humans is found to be contagious and transmissible among humans, as it is in cervids [57], the spread of the disease within humans might become endemic.

Transmission of cervid prions to humanized mice demonstrates the zoonotic potential of CWD

Acta Neuropathol 144, 767–784 (2022). https://doi.org/10.1007/s00401-022-02482-9

Published

22 August 2022


Fortuitous generation of a zoonotic cervid prion strain

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.


The finding that infectious PrPSc was shed in fecal material of CWD-infected humanized mice and induced clinical disease, different tropism, and typical three banding pattern-PrPres in bank voles that is transmissible upon second passage is highly concerning for public health. The fact that this biochemical signature in bank voles resembles that of the Wisc-1 original deer isolate and is different from that of bvWisc-1, in the migration profile and the glyco-form-ratio, is valid evidence that these results are not a product of contamination in our study. If CWD in humans is found to be contagious and transmissible among humans, as it is in cervids [57], the spread of the disease within humans might become endemic.

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.

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.

“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


snip...see full text;


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.


''The brain of diseased Tg mice reveals the electrophoretic profile of PrPSc similar to sporadic Creutzfeldt-Jakob disease (sCJD) MM1 or VV2 subtype but different neuropathological patterns.''

''We believe that our study provides the first evidence that CWD PrPSc is able to convert human PrPC into PrPSc in vitro and the CWD-derived human PrPSc mimics atypical sCJD subtypes in humanized Tg mice.''

Published: 26 September 2021

Generation of human chronic wasting disease in transgenic mice

Zerui Wang, Kefeng Qin, Manuel V. Camacho, Ignazio Cali, Jue Yuan, Pingping Shen, Justin Greenlee, Qingzhong Kong, James A. Mastrianni & Wen-Quan Zou

Acta Neuropathologica Communications volume 9, Article number: 158 (2021)

Abstract

Chronic wasting disease (CWD) is a cervid prion disease caused by the accumulation of an infectious misfolded conformer (PrPSc) of cellular prion protein (PrPC). It has been spreading rapidly in North America and also found in Asia and Europe. Although bovine spongiform encephalopathy (i.e. mad cow disease) is the only animal prion disease known to be zoonotic, the transmissibility of CWD to humans remains uncertain. Here we report the generation of the first CWD-derived infectious human PrPSc by elk CWD PrPSc-seeded conversion of PrPC in normal human brain homogenates using in vitro protein misfolding cyclic amplification (PMCA). Western blotting with human PrP selective antibody confirmed that the PMCA-generated protease-resistant PrPSc was derived from the human PrPC substrate. Two lines of humanized transgenic mice expressing human PrP with either Val or Met at the polymorphic codon 129 developed clinical prion disease following intracerebral inoculation with the PMCA-generated CWD-derived human PrPSc. Diseased mice exhibited distinct PrPSc patterns and neuropathological changes in the brain. Our study, using PMCA and animal bioassays, provides the first evidence that CWD PrPSc can cross the species barrier to convert human PrPC into infectious PrPSc that can produce bona fide prion disease when inoculated into humanized transgenic mice.

Snip...

It is worth noting that the annual number of sporadic CJD (sCJD) cases in the USA has increased, with the total number of suspected and confirmed sCJD cases rising from 284 in 2003 to 511 in 2017 (https://www.cdc.gov/prions/cjd/occurrence-transmission.html). The greatly enhanced CJD surveillance and an aging population in the USA certainly contributed to the observed increase in annual sCJD case numbers in recent years, but the possibility cannot be excluded that some of the increased sCJD prevalence is linked to CWD exposure.

In the present study, using serial protein misfolding cyclic amplification (sPMCA) assay we generate PrPSc by seeding CWD prions in normal human brain homogenates. Importantly, we reveal that two lines of humanized Tg mice expressing human PrP-129VV and 129MM develop prion diseases upon intracerebral inoculation of the abnormal PrP generated by sPMCA. We believe that our study provides the first opportunity to dissect the clinical, pathological and biochemical features of the CWD-derived human prion disease in two lines of humanized Tg mice expressing two major human PrP genotypes, respectively.


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


*** 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”

From: TSS 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

-----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

However, to date, no CWD infections have been reported in people.

sporadic, spontaneous CJD, 85%+ of all human TSE, did not just happen. never in scientific literature has this been proven. if one looks up the word sporadic or spontaneous at pubmed, you will get a laundry list of disease that are classified in such a way;

sporadic = 54,983 hits


spontaneous = 325,650 hits


key word here is 'reported'. science has shown that CWD in humans will look like sporadic CJD.

SO, how can one assume that CWD has not already transmitted to humans? they can't, and it's as simple as that. from all recorded science to date, CWD has already transmitted to humans, and it's being misdiagnosed as sporadic CJD. ...terry

*** LOOKING FOR CWD IN HUMANS AS nvCJD or as an ATYPICAL CJD, LOOKING IN ALL THE WRONG PLACES $$$ *** However, to date, no CWD infections have been reported in people. key word here is ‘reported’. science has shown that CWD in humans will look like sporadic CJD. SO, how can one assume that CWD has not already transmitted to humans? they can’t, and it’s as simple as that. from all recorded science to date, CWD has already transmitted to humans, and it’s being misdiagnosed as sporadic CJD. …terry

*** LOOKING FOR CWD IN HUMANS AS nvCJD or as an ATYPICAL CJD, LOOKING IN ALL THE WRONG PLACES $$$ ***

*** 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).***




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

Consumption of venison and veal was much less widespread among both cases and controls. For both of these meats there was evidence of a trend with increasing frequency of consumption being associated with increasing risk of CJD. (not nvCJD, but sporadic CJD...tss) These associations were largely unchanged when attention was restricted to pairs with data obtained from relatives. ...

Table 9 presents the results of an analysis of these data.

There is STRONG evidence of an association between ‘’regular’’ veal eating and risk of CJD (p = .0.01).

Individuals reported to eat veal on average at least once a year appear to be at 13 TIMES THE RISK of individuals who have never eaten veal.

There is, however, a very wide confidence interval around this estimate. There is no strong evidence that eating veal less than once per year is associated with increased risk of CJD (p = 0.51).

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).

There is some evidence that risk of CJD INCREASES WITH INCREASING FREQUENCY OF LAMB EATING (p = 0.02).

The evidence for such an association between beef eating and CJD is weaker (p = 0.14). When only controls for whom a relative was interviewed are included, this evidence becomes a little STRONGER (p = 0.08).

snip...

It was found that when veal was included in the model with another exposure, the association between veal and CJD remained statistically significant (p = < 0.05 for all exposures), while the other exposures ceased to be statistically significant (p = > 0.05).

snip...

In conclusion, an analysis of dietary histories revealed statistical associations between various meats/animal products and INCREASED RISK OF CJD. When some account was taken of possible confounding, the association between VEAL EATING AND RISK OF CJD EMERGED AS THE STRONGEST OF THESE ASSOCIATIONS STATISTICALLY. ...

snip...

In the study in the USA, a range of foodstuffs were associated with an increased risk of CJD, including liver consumption which was associated with an apparent SIX-FOLD INCREASE IN THE RISK OF CJD. By comparing the data from 3 studies in relation to this particular dietary factor, the risk of liver consumption became non-significant with an odds ratio of 1.2 (PERSONAL COMMUNICATION, PROFESSOR A. HOFMAN. ERASMUS UNIVERSITY, ROTTERDAM). (???...TSS)

snip...see full report ;




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 ############

BSE INQUIRY

CJD9/10022

October 1994

Mr R.N. Elmhirst Chairman British Deer Farmers Association Holly Lodge Spencers Lane

BerksWell Coventry CV7 7BZ

Dear Mr Elmhirst,

CREUTZFELDT-JAKOB DISEASE (CJD) SURVEILLANCE UNIT REPORT

Thank you for your recent letter concerning the publication of the third annual report from the CJD Surveillance Unit. I am sorry that you are dissatisfied with the way in which this report was published.

The Surveillance Unit is a completely independant outside body and the Department of Health is committed to publishing their reports as soon as they become available. In the circumstances it is not the practice to circulate the report for comment since the findings of the report would not be amended.. In future we can ensure that the British Deer Farmers Association receives a copy of the report in advance of publication.

The Chief Medical Officer has undertaken to keep the public fully informed of the results of any research in respect of CJD. This report was entirely the work of the unit and was produced completely independantly of the the Department.

The statistical results reqarding the consumption of venison was put into perspective in the body of the report and was not mentioned at all in the press release. Media attention regarding this report was low key but gave a realistic presentation of the statistical findings of the Unit. This approach to publication was successful in that consumption of venison was highlighted only once by the media ie. in the News at one television proqramme.

I believe that a further statement about the report, or indeed statistical links between CJD and consumption of venison, would increase, and quite possibly give damaging credence, to the whole issue. From the low key media reports of which I am aware it seems unlikely that venison consumption will suffer adversely, if at all.


TSE in wild UK deer? The first case of BSE (as we now realise) was in a nyala in London zoo and the further zoo cases in ungulates were simply thought of as being interesting transmissions of scrapie initially. The big problem started to appear with animals in 1993-5 when it became clear that there was an increase in the CJD cases in people that had eaten deer although the statistics involved must have been questionable. The reason for this was that the CJD Surveillance was well funded to look into the diet of people dying of CJD. This effect is not clear with vCJD...if only because the numbers involved are much smaller and hence it is difficult to gain enough statistics. They found that many other foods did not appear to have much association at all but that deer certainly did and as years went by the association actually became clearer. The appearance of vCJD in 1996 made all this much more difficult in that it was suddenly clearer that the cases of sporadic CJD that they had been checking up until then probably had nothing to do with beef...and the study decreased. During the period there was an increasing worry that deer were involved with CJD..

see references:

DEER BRAIN SURVEY


CONFIDENTIAL AND IN CONFIDENCE TRANSMISSION TO CHIMPANZEES AND PIGS

IN CONFIDENCE

TRANSMISSION TO CHIMPANZEES

Kuru and CJD have been successfully transmitted to chimpanzees but scrapie and TME have not.

We cannot say that scrapie will not transmit to chimpanzees. There are several scrapie strains and I am not aware that all have been tried (that would have to be from mouse passaged material). Nor has a wide enough range of field isolates subsequently strain typed in mice been inoculated by the appropriate routes (i/c, i/p and i/v).

I believe the proposed experiment to determine transmissibility, if conducted, would only show the susceptibility or resistance of the chimpanzee to infection/disease by the routes used and the result could not be interpreted for the predictability of the susceptibility for man. proposals for prolonged oral exposure of chimpanzees to milk from cattle were suggested a long while ago and rejected.

In view of Dr Gibbs' probable use of chimpazees Mr Wells' comments (enclosed) are pertinent. I have yet to receive a direct communication from Dr Schellekers but before any collaboration or provision of material we should identify the Gibbs' proposals and objectives.

A positive result from a chimpanzee challenged severely 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.

A negative result would take a lifetime to determine but that would be a shorter period than might be available for human exposure and it would still not answer the question regarding mans ‘susceptibility. In the meantime no doubt the negativity would be used defensively. It would however be counterproductive if the experiment finally became positive. We may learn more about public reactions following next Monday's meeting.

R Bradley

CVO (+ Mr Wells’ commenters 23 September 1990 Dr T W A Little Dr B J Shreeve

90/9.23/1.1


Snip…END

SUNDAY, MARCH 23, 2025

Creutzfeldt Jakob Disease TSE Prion Increasing 2025 Update




To be continued…

Terry S. Singeltary Sr.

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