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

Mr. Reed, please, here is my updated submission, with some updated cwd tse prp science...thank you, and thanks for all the work TPWD et al are doing trying to contain cwd...kind regards, terry

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

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

Proposed Amendments to Disease Management and Response Regulations – Chronic Wasting Disease Comment online through 05:00 p.m. November 1, 2023.

Staff seeks adoption of proposed amendments to rules governing chronic wasting disease (CWD) detection, response, and management, and deer breeder permits.

The proposed amendments are intended to function collectively to refine surveillance and investigation efforts as part of the agency’s effort to manage CWD and would:

require ante-mortem (live-animal) testing of test-eligible deer prior to transfer from a breeding facility to another breeding facility; YES AGREE!...TSS

reproduce the statutory provisions governing the required permanent identification tags on breeder deer; YES AGREE!...TSS

provide for the transport of deer carcasses from CWD management zones to a final destination or taxidermist, provided a Texas Parks and Wildlife Department (TPWD)-issued check station receipt has been obtained; YES AGREE, but concerned with movement of any cervid from CWD management zones...TSS

impose statewide carcass disposal measures; YES AGREE, but concerned with the methods of disposal that have been put into place...TSS

eliminate provisions allowing deer breeders to transfer fawns to external facilities for nursing purposes; YES, AGREE!...TSS

impose a residency requirement on breeder deer as a condition of transfer to another breeding facility or to a release site; YES, AGREE!...TSS

impose seven-day deadline for submission of CWD test samples for Trap, Transport and Process permits; YES, AGREE!...TSS

prohibit the release of breeder deer prior to April 1 of the year following birth; YES, AGREE!...TSS

remove the three-year sunset of provisions governing the ante-mortem testing of breeder deer prior to release; YES, AGREE...TSS

strengthen provisions governing the obligations of release-site owners in the event a release site becomes epidemiologically linked to a CWD-positive deer breeding facility; YES, AGREE!...TSS

and

provide for the suspension of Managed Lands Deer Program (MLDP) privileges for landowners who fail to comply with harvest, testing, and recordkeeping requirements at release sites epidemiologically linked to a CWD-positive deer breeding facility. YES, AGREE...TSS

The proposed amendment to §65.88, concerning Deer Carcass Movement Restrictions, would streamline and simplify regulations governing the post-harvest transportation of deer taken by hunters in CWD management zones. Because CWD prions (the infectious agents that causes CWD) are known to be present in tissues of infected animals, especially brain, spinal cord and viscera, the department believes that care should be taken with respect to the treatment of carcasses of animals taken within a CWD management zone. Under current rule, a deer taken in a CWD management zone cannot be transported from the zone unless it has been processed as required by the section. The department has determined that the current rules can be modified to allow the movement of unprocessed carcasses from management zones to a final destination (the possessor’s permanent residence or cold storage/processing facility) or taxidermist, provided it has been first presented at a department check station for tissue sample removal, which will allow the department to conduct disease surveillance and provide a method for notifying hunters in the event that an animal tests positive for CWD. The proposed amendment would also impose statewide carcass disposal measures, to consist of disposal of all deer parts not retained for cooking, storage, or taxidermy purposes to be disposed of (directly or indirectly) at a landfill permitted by the Texas Commission on Environmental Quality to receive such wastes, by interment at a depth of no less than three feet below the natural surface of the ground and covered with at least three feet of earthen material, or by being returned to the property where the animal was harvested. The department has determined that in light of the recent spate of CWD detections in deer breeding facilities (which are extensively epidemiologically interconnected and the source of deer released at hundreds of locations across the state), a statewide carcass disposal rule will be beneficial by limiting and ideally eliminating the careless, haphazard, or inadequate disposal of potentially infectious tissues, thus mitigating the potential spread of CWD.

https://tpwd.texas.gov/business/feedback/public_comment/proposals/202311_cwd.phtml

“You can throw it in a dumpster that goes to a trash service that goes to a permitted landfill. Most all trash services I know of that have dumpsters go into some sort of permitted landfill,” Cain said. “That’s one option.”

The landfill would have to be permitted by the Texas Commission on Environmental Quality (TCEQ) to receive such wastes.

“If you don’t have that option, you could bury those unused carcass parts in your backyard or back pasture,” Cain said. “You could bury them as long as they’re three feet deep and covered by soil so you’re not letting scavengers grab those carcass parts and draft them across the landscape.”

Burying the unused deer carcass parts won’t be an option in all parts of Texas due to rocks and other issues. Cain said that’s why the rule includes three options for hunters.

The third option is returning the unused parts to the property where the deer was harvested.

“It doesn’t really change things a lot for a hunter other than where you can dispose of it,” Cain said. “If you’re not the type of person who processes your own deer, you can still take it to a locker plant, and then they would be responsible for disposing of those parts in a landfill, trash service or bury it.”

The rule would provide some flexibility for those who hunt in CWD containment or surveillance zones.

“If you’re in a CWD zone and you harvest a deer, under the proposal, you’ll be able to take a whole carcass out. Currently, you can’t do that,” Cain said. “Before you leave the zone through, you’d have to stop by the check station and let us test the deer, which is required by rule. Then, we could provide instructions.”

Hunters would still be able to quarter deer on the property where they’re hunting and take it home to finish processing it.

“Under the proposal, you’d still need to throw those bones away in the dumpster or bury it, but you could still quarter it at the ranch and do that before you take off,” Cain said.

Those who do not plan to remove the deer they’ve harvested from the site of harvest will see no change if the rule is implemented.

“It’s just when you’re moving a carcass off the ranch (or hunting location) to another location, that’s where these proposed rules would come into effect,” Cain said.

The rule, if implemented, would impact deer hunters statewide, not just those in CWD containment or surveillance zones.

https://texasfarmbureau.org/tpwd-proposes-statewide-deer-carcass-disposal-rule/

Singeltary further comments on disposal methods of cervid carcasses;

my main concerns are with the methods of disposal. i have seen some disposal dumpsters for cervid in some states that are extremely unsafe for the CWD TSE Prion. With all the tissues, and BLOOD, that has been proven to show infectivity, just throwing a bunch of potentially exposed cervid to cwd in the dipsy dumpster can be dangerous. burying carcass parts only three feet can be dangerous for surrounding areas, from scavengers, and water tables. these dumpsters must be lined with no drainage, with liner being properly disposed of as well, and preferably, the preferred method of disposal for TSE Prion is INCINERATION! as well, i think that a total ban on movement of any cervid from Breeders, Game Farms, should be banned altogether, until a validated CWD test can be used on any and all cervid every time they are moved...

recent science shows;

SUBJECT MATTER: 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.

https://www.usaha.org/upload/Resolution/2022/2022_Resolution_30_CWD_Dumpste.pdf

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

https://doi.org/10.1016/j.rvsc.2020.10.009

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.

Abstract

Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy (TSEs) that affects free-ranging and captive cervid species. The infectious agent of CWD may be transmitted from ingestion of prions shed in bodily fluids (e.g. feces, urine, saliva, placenta tissue) of infected animals, contaminated pastures, and/or decomposing carcasses from dead animals. Studies have also demonstrated prion infectivity in whole blood or blood fractions of CWD infected animals. To determine if CWD-infected blood contained sufficient levels of prion infectivity to cause disease, recipient deer were inoculated intravenously (IV) with blood derived from a CWD-infected white-tailed deer. We found that the CWD agent can be successfully transmitted to white-tailed deer by a single intravenous blood transfusion. The incubation period was associated with recipient prion protein genotype at codon 96 with the GG96 recipient incubating for 25.6 months and the GS96 recipient incubating for 43.6 months. This study complements and supports an earlier finding that CWD can be transmitted to deer by intravenous blood transfusion from white-tailed deer with CWD.

SNIP...

We demonstrate here that the CWD agent can be successfully transmitted to white-tailed deer by a single intravenous blood transfusion from CWD-infected white-tailed deer. The incubation period appeared to be associated with recipient genotype with the GG96 deer (940) incubating for 25.6 months, while the GS96 deer (941) incubated for 43.6 months; however, we take into consideration the limitation of the small sample size in this study. While a previous and larger study showed similar results, we determined that only 100 mL of CWD-infected blood (~2.5 times less than previously shown in (Mathiason et al., 2010)) contained sufficient levels of prion infectivity to cause disease. The identification of blood-borne transmission of the CWD agent is important in reinforcing the risk of exposure to CWD via blood as well as the possibility of hematogenous transmission of the CWD agent through insect vector. Finally, these results further highlight the importance of developing a sensitive and reproducible blood-based test to detect pre-clinical CWD, and warrant the continued advancement and evaluation of sensitive antemortem diagnostic tests for the detection of PrPSc in blood of asymptomatic cervids early in the incubation period.

Keywords

Blood transfusion Cervid CWD Prion disease Prions in blood White-tailed deer

https://www.sciencedirect.com/science/article/pii/S003452882031047X?via%3Dihub

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

Detection of prions in soils contaminated by multiple routes

Stuart Siegfried Lichtenberg1,2 , Heather Inzalaco3 , Sam Thomas4 , Dan Storm5 , Dan Walsh6

1Department of Veterinary and Biomedical Sciences, University of Minnesota, St. Paul, Minnesota, U.S.A. 2Minnesota Center for Prion Research and Outreach, University of Minnesota, St. Paul, Minnesota, U.S.A. 3 Wisconsin Cooperative Wildlife Research Unit, Department of Forest and Wildlife Ecology, University of Wisconsin-Madison, Madison, Wisconsin, U.S.A 4Department of Soil Science, University of Wisconsin-Madison, Madison, Wisconsin, U.S.A. 5Wisconsin Department of Natural Resources, Eau Claire, Wisconsin, U.S.A. 6U.S. Geological Survey, Montana Cooperative Wildlife Research Unit, University of Montana, Missoula, Montana, U.S.A.

Aims: Free-ranging animals afflicted with transmissible spongiform encephalopathies frequently shed infectious prions into the broader environment. The quintessential example is chronic wasting disease, the TSE of cervids. Over the course of the disease, an infected animal will shed infectious prions in blood, urine, saliva, and feces. Upon death, the total prion load interred in the animal’s tissues will be deposited wherever the animal falls. This contamination creates substantial risk to naïve animals, and likely contributes to disease spread. Identification and quantification of prions at contamination hotspots is essential for any attempt at mitigation of environmental transmission.

Materials and Methods: Surfactant extraction of soils followed by precipitation yields a sample that is amenable to analysis by real-time quaking induced conversion. However, differences in extraction yield are apparent depending on the properties of the matrix from which the prions are being extracted, principally soil clay content.

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

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

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

Presenting author: Tiffany M. Wolf 1 Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, St. Paul, Minnesota, USA 2 Minnesota Center for Prion Research and Outreach, College of Veterinary Medicine, University of Minnesota, St. Paul, Minnesota, USA 3 Department of Medical Microbiology and Immunology, School of Medicine, Creighton University, Omaha, Nebraska, USA 4 Department of Veterinary Population Medicine, College of Veterinary Medicine, University of Minnesota, St. Paul, Minnesota, USA

Aims: There is a growing concern that chronic wasting disease (CWD) prions in venison pose a risk to human health. CWD prions accumulate in infected deer tissues that commonly enter the human food chain through meat processing and consumption. The United States (US) Food and Drug Administration and US Department of Agriculture now formally consider CWD-positive venison unfit for human and animal consumption. Yet, the degree to which prion contamination occurs during routine venison processing is unknown. Here, we use environmental surface swab methods to: a) experimentally test meat processing equipment (i.e., stainless steel knives and polyethylene cutting boards) before and after processing CWD-positive venison and b) test the efficacy of five different disinfectant types (i.e., Dawn dish soap, Virkon-S, Briotech, 10% bleach, and 40% bleach) to determine prion decontamination efficacy.

Materials and Methods: We used a real-time quaking-induced conversion (RT-QuIC) assay to determine CWD infection status of venison and to detect CWD prions in the swabs. We collected three swabs per surface and ran eight technical replicates on RT-QuIC.

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.

Acknowledgement: Funding was provided by the Minnesota Environment and Natural Resources Trust Fund as recommended by the Legislative-Citizen Commission on Minnesota Resources (LCCMR), the Rapid Agriculture Response Fund (#95385/RR257), and the Michigan Department of Natural Resources.

Theme: Animal prion diseases

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Prion 2023 Abstracts

https://prion2023.org/wp-content/uploads/2023/10/Meeting-book-final-version2.pdf

***> 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."

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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."

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https://prion2023.org/wp-content/uploads/2023/10/Meeting-book-final-version2.pdf

MONDAY, OCTOBER 16, 2023

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

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

https://chronic-wasting-disease.blogspot.com/2023/10/transmission-of-chronic-wasting-disease.html

PRION 2023 CONTINUED;

https://prion2023.org/wp-content/uploads/2023/10/Meeting-book-final-version2.pdf

Detection of chronic wasting disease prions in processed meats

Rebeca Benavente1 , Francisca Bravo1,2, J. Hunter Reed3 , Mitch Lockwood3 , Glenn Telling4 , Rodrigo Morales1,2 1 Department of Neurology, McGovern Medical School, University of Texas Health Science Center at Houston, Texas, USA; 2 Universidad Bernardo O’Higgins. Santiago, Chile; 3 Texas Parks and Wildlife Department, Texas, USA. 4 Prion Research Center, Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, CO, USA

Aims: identify the presence of CWD prions in processed meats derived from elk.

Materials and Methods: In this study, we analyzed different processed meats derived from a CWD-positive (pre-clinical) free-ranging elk. Products tested included filets, sausages, boneless steaks, burgers, seasoned chili meats, and spiced meats. The presence of CWD-prions in these samples were assessed by PMCA using deer and elk substrates. The same analyses were performed in grilled and boiled meats to evaluate the resistance of the infectious agent to these procedures.

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.

Funded by: NIH and USDA

Grant number: 1R01AI132695 and APP-20115 to RM

Acknowledgement: We would like to thank TPWD personnel for providing us with valuable samples

"Our results show positive prion detection in all the samples analyzed using deer and elk substrates. Surprisingly, cooked meats displayed increased seeding activities."

end...

PRION 2023 CONTINUED;

https://prion2023.org/wp-content/uploads/2023/10/Meeting-book-final-version2.pdf

Fortuitous generation of a zoonotic cervid prion strain

Manuel Camacho, Xu Qi, Liuting Qing, Sydney Smith, Jieji Hu, Wanyun Tao, Ignazio Cali, Qingzhong Kong. Department of Pathology, Case Western Reserve University, Cleveland, USA

Aims: Whether CWD prions can infect humans remains unclear despite the very substantial scale and long history of human exposure of CWD in many states or provinces of USA and Canada. Multiple in vitro conversion experiments and in vivo animal studies indicate that the CWD-to-human transmission barrier is not unbreakable. A major long-term public health concern on CWD zoonosis is the emergence of highly zoonotic CWD strains. We aim to address the question of whether highly zoonotic CWD strains are possible.

Materials and Methods: We inoculated several sCJD brain samples into cervidized transgenic mice (Tg12), which were intended as negative controls for bioassays of brain tissues from sCJD cases who had potentially been exposed to CWD. Some of the Tg12 mice became infected and their brain tissues were further examined by Western blot as well as serial passages in humanized or cervidized mice.

Results: Passage of sCJDMM1 in transgenic mice expressing elk PrP (Tg12) resulted in a “cervidized” CJD strain that we termed CJDElkPrP. We observed 100% transmission of the original CJDElkPrP in transgenic mice expressing human PrP. We passaged CJDElkPrP two more times in the Tg12 mice. We found that such second and third passage CJDElkPrP prions retained 100% transmission rate in the humanized mice, despite that the natural elk CWD isolates and CJDElkPrP share the same elk PrP sequence. In contrast, we and others found zero or poor transmission of natural elk CWD isolates in humanized mice.

Conclusions: Our data indicate that highly zoonotic cervid prion strains are not only possible but also can retain zoonotic potential after serial passages in cervids, suggesting a very significant and serious long-term risk of CWD zoonosis given that the broad and continuing spread of CWD prions will provide fertile grounds for the emergence of zoonotic CWD strains over time.

Funded by: NIH Grant number: R01NS052319, R01NS088604, R01NS109532

Acknowledgement: We want to thank the National Prion Disease Pathology Surveillance Center and Drs. Allen Jenny and Katherine O'Rourke for providing the sCJD samples and the CWD samples used in this study, respectively

"Our data indicate that highly zoonotic cervid prion strains are not only possible but also can retain zoonotic potential after serial passages in cervids, suggesting a very significant and serious long-term risk of CWD zoonosis given that the broad and continuing spread of CWD prions will provide fertile grounds for the emergence of zoonotic CWD strains over time."

PRION 2023 CONTINUED;

https://prion2023.org/wp-content/uploads/2023/10/Meeting-book-final-version2.pdf

A probable diagnostic marker for CWD infection in humans

Xu Qi, Liuting Qing, Manuel Camacho, Ignazio Cali, Qingzhong Kong. Department of Pathology, Case Western Reserve University, Cleveland, USA

Aims: Multiple in vitro CWD-seeded human PrP conversion experiments and some animal model studies indicate that the species barrier for CWD to human transmission can be overcome, but whether CWD prion can infect humans in real life remains controversial. The very limited understanding on the likely features of CWD infection in humans and the lack of a reliable diagnostic marker for identification of acquired human CWD cases contribute to this uncertainty. We aim to stablish such a reliable diagnostic marker for CWD infections in humans should they occur.

Materials and Methods: A couple of PrPSc-positive spleens were identified from humanized transgenic mice inoculated with either CWD or sCJDMM1. Prions in these spleens were compared by bioassays in cervidized or humanized transgenic mice. A couple of PrPSc-positive spleens from UK sCJDMM1 patients were also examined similarly as controls with no exposure to CWD.

Results: We have detected two prion-positive spleens in humanized transgenic mice inoculated with some CWD isolates. Such experimentally generated splenic “humanized” CWD prions (termed eHuCWDsp) appear indistinguishable from prions in the brain of sCJDMM1 patients on Western blot. We compared eHuCWDsp with prions in the spleen from humanized mice infected with sCJDMM1 (termed sCJDMM1sp) by bioassays in cervidized or humanized transgenic mice. Significantly, we found that eHuCWDsp can efficiently infect not only the humanized mice but also cervidized transgenic mice, and cervidized mice infected by eHuCWDsp produced PrPSc and brain pathology that are practically identical to those of CWD-infected cervidized mice. In contrast, sCJDMM1sp, similar to prions from sCJDMM1 patient brains, is poorly transmissible in the cervidized mice.

Conclusions: Our data demonstrate that high transmissibility with CWD features of splenic prions in cervidized transgenic mice is unique to acquired human CWD prions, and it may serve as a reliable marker to identify the first acquired human CWD cases.

Funded by: NIH Grant number: R01NS052319, R01NS088604, R01NS109532

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PRION 2023 CONTINUED;

https://prion2023.org/wp-content/uploads/2023/10/Meeting-book-final-version2.pdf

Prion 2023 Experimental Oronasal Inoculation of the Chronic Wasting Disease Agent into White Tailed Deer

Author list: Sarah Zurbuchena,b , S. Jo Moorea,b , Jifeng Biana , Eric D. Cassmanna , and Justin J. Greenleea . a. Virus and Prion Research Unit, National Animal Disease Center, ARS, United States Department of Agriculture, Ames, IA, US b. Oak Ridge Institute for Science and Education (ORISE), U.S. Department of Energy, Oak Ridge, TN, United States

Aims: The purpose of this experiment was to determine whether white-tailed deer (WTD) are susceptible to inoculation of chronic wasting disease (CWD) via oronasal exposure.

Materials and methods: Six male, neutered WTD were oronasally inoculated with brainstem material (10% w/v) from a CWD-positive wild-type WTD. The genotypes of five inoculated deer were Q95/G96 (wild-type). One inoculated deer was homozygous S at codon 96 (96SS). Cervidized (Tg12; M132 elk PrP) mice were inoculated with 1% w/v brainstem homogenate from either a 96GG WTD (n=10) or the 96SS WTD (n=10).

Results: All deer developed characteristic clinical signs of CWD including weight loss, regurgitation, and ataxia. The 96SS individual had a prolonged disease course and incubation period compared to the other deer. Western blots of the brainstem on all deer yielded similar molecular profiles. All deer had widespread lymphoid distribution of PrPCWD and neuropathologic lesions associated with transmissible spongiform encephalopathies. Both groups of mice had a 100% attack rate and developed clinical signs, including loss of body condition, ataxia, and loss of righting reflex. Mice inoculated with material from the 96SS deer had a significantly shorter incubation period than mice inoculated with material from 96GG deer (Welch two sample T-test, P<0.05). Serial dilutions of each inocula suggests that differences in incubation period were not due to a greater concentration of PrPCWD in the 96SS inoculum. Molecular profiles from western blot of brain homogenates from mice appeared similar regardless of inoculum and appear similar to those of deer used for inoculum.

Conclusions: This study characterizes the lesions and clinical course of CWD in WTD inoculated in a similar manner to natural conditions. It supports previous findings that 96SS deer have a prolonged disease course. Further, it describes a first pass of inoculum from a 96SS deer in cervidized mice which shortened the incubation period.

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

Acknowledgement: We thank Ami Frank and Kevin Hassall for their technical contributions to this project.

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PRION 2023 CONTINUED;

https://prion2023.org/wp-content/uploads/2023/10/Meeting-book-final-version2.pdf

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

Marissa S. Milstein1,2, Marc D. Schwabenlander1,2, Sarah C. Gresch1,2, Manci Li1,2, Stuart Lichtenberg1,2, Rachel Shoemaker1,2, Gage R. Rowden1,2, Jason C. Bartz2,3 , Tiffany M. Wolf2,4, Peter A. Larsen1,2 Presenting author: Tiffany M. Wolf 1 Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, St. Paul, Minnesota, USA 2 Minnesota Center for Prion Research and Outreach, College of Veterinary Medicine, University of Minnesota, St. Paul, Minnesota, USA 3 Department of Medical Microbiology and Immunology, School of Medicine, Creighton University, Omaha, Nebraska, USA 4 Department of Veterinary Population Medicine, College of Veterinary Medicine, University of Minnesota, St. Paul, Minnesota, USA

Theme: Animal prion diseases

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PRION 2023 CONTINUED;

https://prion2023.org/wp-content/uploads/2023/10/Meeting-book-final-version2.pdf

Detection of prions in soils contaminated by multiple routes

Stuart Siegfried Lichtenberg1,2 , Heather Inzalaco3 , Sam Thomas4 , Dan Storm5 , Dan Walsh6 1Department of Veterinary and Biomedical Sciences, University of Minnesota, St. Paul, Minnesota, U.S.A. 2Minnesota Center for Prion Research and Outreach, University of Minnesota, St. Paul, Minnesota, U.S.A. 3 Wisconsin Cooperative Wildlife Research Unit, Department of Forest and Wildlife Ecology, University of Wisconsin-Madison, Madison, Wisconsin, U.S.A 4Department of Soil Science, University of Wisconsin-Madison, Madison, Wisconsin, U.S.A. 5Wisconsin Department of Natural Resources, Eau Claire, Wisconsin, U.S.A. 6U.S. Geological Survey, Montana Cooperative Wildlife Research Unit, University of Montana, Missoula, Montana, U.S.A.

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.

Funded by: Wisconsin Department of Natural Resources

"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)."

=====end

PRION 2023 CONTINUED;

https://prion2023.org/wp-content/uploads/2023/10/Meeting-book-final-version2.pdf

17 DETECTION OF CHRONIC WASTING DISEASE PRIONS IN PROCESSED MEATS.

Rebeca Benavente1, Francisca Bravo1,2, Paulina Soto1,2, J. Hunter Reed3, Mitch Lockwood3, Rodrigo Morales1,2

1Department of Neurology, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, USA. 2Universidad Bernardo O’Higgins, Santiago, Chile. 3Texas Parks and Wildlife, Austin, USA

Abstract

The zoonotic potential of chronic wasting disease (CWD) remains unknown. Currently, there are no known natural cases of CWD transmission to humans but increasing evidence suggests that the host range of CWD is not confined only to cervid species. Alarmingly, recent experimental evidence suggests that certain CWD isolates can induce disease in non-human primates. While the CDC strongly recommends determining CWD status in animals prior to consumption, this practice is voluntary. Consequently, it is plausible that a proportion of the cervid meat entering the human food chain may be contaminated with CWD. Of additional concern is that traditional diagnostic techniques used to detect CWD have relatively low sensitivity and are only approved for use in tissues other than those typically ingested by humans. In this study, we analyzed different processed meats derived from a pre-clinical, CWD-positive free-ranging elk. Products tested included filets, sausages, boneless steaks, burgers, ham steaks, seasoned chili meats, and spiced meats. CWD-prion presence in these products were assessed by PMCA using deer and elk substrates.

***> Our results show positive prion detection in all products.

***>To confirm the resilience of CWD-prions to traditional cooking methods, we grilled and boiled the meat products and evaluated them for any remnant PMCA seeding activity. Results confirmed the presence of CWD-prions in these meat products suggesting that infectious particles may still be available to people even after cooking.

***> Our results strongly suggest ongoing human exposure to CWD-prions and raise significant concerns of zoonotic transmission through ingestion of CWD contaminated meat products.

***> Products tested included filets, sausages, boneless steaks, burgers, ham steaks, seasoned chili meats, and spiced meats.

***> CWD-prion presence in these products were assessed by PMCA using deer and elk substrates.

***> Our results show positive prion detection in all products.

***> Results confirmed the presence of CWD-prions in these meat products suggesting that infectious particles may still be available to people even after cooking.

***> Our results strongly suggest ongoing human exposure to CWD-prions and raise significant concerns of zoonotic transmission through ingestion of CWD contaminated meat products.

=====

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

Samia Hannaoui1,2, Ginny Cheng1,2, Wiebke Wemheuer3, Walter Schulz-Schaeffer3, Sabine Gilch1,2, Hermann Schatzl1,2 1University of Calgary, Calgary, Canada. 2Calgary Prion Research Unit, Calgary, Canada. 3Institute of Neuropathology, Medical Faculty, Saarland University, Homburg/Saar, Germany

***> Further passage to cervidized mice revealed transmission with a 100% attack rate.

***> Our findings demonstrate that macaques, considered the best model for the zoonotic potential of prions, were infected upon CWD challenge, including the oral one.

****> The disease manifested as atypical in macaques and initial transgenic mouse transmissions, but with infectivity present at all times, as unveiled in the bank vole model with an unusual tissue tropism.

***> Epidemiologic surveillance of prion disease among cervid hunters and people likely to have consumed venison contaminated with chronic wasting disease

=====

https://intcwdsympo.files.wordpress.com/2023/06/final-agenda-with-abstracts.pdf?force_download=true

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 scrapiepositive 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.

https://bvajournals.onlinelibrary.wiley.com/doi/abs/10.1136/vr.105054

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

https://pubmed.ncbi.nlm.nih.gov/30602491/

***> 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

https://www.microbiologyresearch.org/content/journal/jgv/10.1099/vir.0.82011-0

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.

http://journal.frontiersin.org/article/10.3389/fvets.2015.00032/full

172. Establishment of PrPCWD extraction and detection methods in the farm soil

Conclusions: Our studies showed that PrPCWD persist in 0.001% CWD contaminated soil for at least 4 year and natural CWD-affected farm soil. When cervid reintroduced into CWD outbreak farm, the strict decontamination procedures of the infectious agent should be performed in the environment of CWD-affected cervid habitat.

https://www.tandfonline.com/doi/full/10.1080/19336896.2019.1615197

THE 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 with.

***> that’s what’s so worrisome about Iatrogenic mode of transmission, a simple autoclave will not kill this TSE prion agent.

1: J Neurol Neurosurg Psychiatry 1994 Jun;57(6):757-8

***> 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.

PMID: 8006664 [PubMed - indexed for MEDLINE]

https://www.ncbi.nlm.nih.gov/pubmed/8006664?dopt=Abstract

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

http://www.pnas.org/content/97/7/3418.full

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

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2493038/

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

https://www.ncbi...nlm.nih.gov/pmc/articles/PMC2802782/pdf/prion0303_0171.pdf

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

http://onlinelibrary.wiley.com/doi/10.1111/j.1539-6924.2012.01922.x/abstract

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

https://bmcvetres.biomedcentral.com/track/pdf/10.1186/1746-6148-9-134.pdf

THURSDAY, FEBRUARY 28, 2019

BSE infectivity survives burial for five years with only limited spread

https://link.springer.com/content/pdf/10.1007%2Fs00705-019-04154-8.pdf

5 or 6 years quarantine is NOT LONG ENOUGH FOR CWD TSE PRION !!!

QUARANTINE NEEDS TO BE 21 YEARS FOR CWD TSE PRION !

FRIDAY, APRIL 30, 2021

Should Property Evaluations Contain Scrapie, CWD, TSE PRION Environmental Contamination of the land?

***> 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 early BSE days---end...tss

and so it seems...

Scrapie Agent (Strain 263K) Can Transmit Disease via the Oral Route after Persistence in Soil over Years

Published: May 9, 2007

snip...

Our results showed that 263K scrapie agent can persist in soil at least over 29 months. Strikingly, not only the contaminated soil itself retained high levels of infectivity, as evidenced by oral administration to Syrian hamsters, but also feeding of aqueous soil extracts was able to induce disease in the reporter animals. We could also demonstrate that PrPSc in soil, extracted after 21 months, provides a catalytically active seed in the protein misfolding cyclic amplification (PMCA) reaction. PMCA opens therefore a perspective for considerably improving the detectability of prions in soil samples from the field.

snip...

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0000435

Dr. Paul Brown Scrapie Soil Test BSE Inquiry Document

https://web.archive.org/web/20090505211734/http://www.bseinquiry.gov.uk/files/sc/Seac07/tab03.pdf

Friday, December 14, 2012

DEFRA U.K. What is the risk of Chronic Wasting Disease CWD being introduced into Great Britain? A Qualitative Risk Assessment October 2012

snip...

In summary, in endemic areas, there is a medium probability that the soil and surrounding environment is contaminated with CWD prions and in a bioavailable form. In rural areas where CWD has not been reported and deer are present, there is a greater than negligible risk the soil is contaminated with CWD prion.

snip...

In summary, given the volume of tourists, hunters and servicemen moving between GB and North America, the probability of at least one person travelling to/from a CWD affected area and, in doing so, contaminating their clothing, footwear and/or equipment prior to arriving in GB is greater than negligible. For deer hunters, specifically, the risk is likely to be greater given the increased contact with deer and their environment. However, there is significant uncertainty associated with these estimates.

snip...

Therefore, it is considered that farmed and park deer may have a higher probability of exposure to CWD transferred to the environment than wild deer given the restricted habitat range and higher frequency of contact with tourists and returning GB residents.

snip...

https://web.archive.org/web/20170404125557/http://webarchive.nationalarchives.gov.uk/20130822084033/http://www.defra.gov.uk/animal-diseases/files/qra_chronic-wasting-disease-121029.pdf

Published: 06 September 2021

***> Chronic wasting disease: a cervid prion infection looming to spillover

Alicia Otero, Camilo Duque Velásquez, Judd Aiken & Debbie McKenzie

Veterinary Research volume 52, Article number: 115 (2021)

https://veterinaryresearch.biomedcentral.com/articles/10.1186/s13567-021-00986-y

2023 CWD ZOONOSIS

PART 2. TPWD CHAPTER 65. DIVISION 1. CWD

31 TAC §§65.82, 65.85, 65.88

The Texas Parks and Wildlife Commission in a duly noticed meeting on May 25, 2023 adopted amendments to 31 TAC §§65.82, 65.85, and §65.88, concerning Disease Detection and Response, without changes to the proposed text as published in the April 21, 2023, issue of the Texas Register (48 TexReg 2048). The rules will not be republished.

Currently, there is scientific evidence to suggest that CWD has zoonotic potential; however, no confirmed cases of CWD have been found in humans.

https://www.sos.texas.gov/texreg/archive/June302023/Adopted%20Rules/31.NATURAL%20RESOURCES%20AND%20CONSERVATION.html#57

Greetings TPWD et al, just a note,

***> STAY VIGELANT WHEN WORKING WITH TAINTED CWD TSE PRION TISSUES! <***

it can happen, it will happen, it does happen, friendly fire, pass it forward, iatrogenic TSE Prion...

kind regards, terry

p.s., please updated the extremely outdated TPWD cwd tracking page, should be pushing 600 cwd positives by now, please update it!

DEGENERATIVE DISEASES

An investigation has been opened into the death of a scientist who was studying a transmissible and deadly disease in Spain

Three institutions are trying to ascertain the origin of the infectious Creutzfeldt-Jakob disease samples discovered in the biochemist’s laboratory. The 45-year-old investigator died in 2022

The University of Barcelona’s School of Medicine, in L’Hospitalet de Llobregat, where laboratory 4141 is located.

MASSILIANO MINOCRI

Manuel Ansede

MANUEL ANSEDE

Madrid - OCT 19, 2023 - 16:15 EDT

A prestigious Spanish researcher of Creutzfeldt-Jakob disease died last year after experiencing symptoms consistent with this deadly ailment, as EL PAÍS has learned from multiple sources at the three institutions involved. Three months ago, the University of Barcelona opened an internal investigation to ascertain the origin of thousands of unauthorized samples, some of them infectious, discovered in a freezer in its laboratory 4141, where the deceased biochemist worked. He was a member of the Bellvitge Biomedical Research Institute (IDIBELL) and the CIBER public consortium. These two institutions have joined the internal investigation, after noting concern among colleagues at the facility, who did not know the level of risk to which they were exposed without their knowledge. This neurodegenerative disease incubates silently for years, but when symptoms appear — rapid dementia and muscle stiffness — it is fatal. Life expectancy after diagnosis is barely six months. Its best-known animal equivalent is mad cow disease.

The biochemist joined the 4141 lab at the University of Barcelona in January 2018 as a principal investigator with a group of his own; his wife joined shortly after. Together, they identified characteristic substances in human cerebrospinal fluid, useful for the diagnosis of rapid dementia. In November 2020, the now deceased scientist began to feel unwell and asked to leave. After his colleagues found out that his symptoms were consistent with Creutzfeldt-Jakob disease, he demanded absolute privacy and decided to hide his diagnosis, according to the sources consulted for this article. He died at the age of 45.

On December 18, 2020, the head of the 4141 laboratory, Isidre Ferrer, a professor of Pathology at the University of Barcelona and a member of IDIBELL, informed the directors of both institutions that suspicious samples of cerebrospinal fluid from people with Creutzfeldt-Jakob disease and other neurodegenerative types of dementia had been discovered by chance in a freezer at 80 degrees below zero, according to internal documentation to which EL PAÍS had access. The thousands of unauthorized samples from patients and animals were in a drawer reserved for the sick researcher’s group and lacked records indicating their presence. The University of Barcelona then ordered the immediate closure and decontamination of laboratory 4141, located in the School of Medicine at L’Hospitalet de Llobregat.

Doctor Gabriel Capellá, the director of IDIBELL, explains that they have identified “a maximum of eight people” who worked in the laboratory at that time, in addition to the deceased scientist and Isidre Ferrer. Some of these coworkers have required months of psychological care. The university’s safety office and IDIBELL’s prevention service determined that there was “an unacceptable risk,” although Capellá emphasizes that “there is no record of any occupational accident” in which a researcher could have been infected with contaminated material. Creutzfeldt-Jakob disease and other human transmissible spongiform encephalopathies are caused by abnormal proteins called prions, which accumulate in the brain and cause a microscopic sponge-like appearance. There are only one or two cases per million inhabitants, the vast majority of which are of unknown cause, but cases of the disease have also been reported after contact with surgical instruments contaminated by these prions.

The three institutions involved took more than two years to send the suspect samples for analysis to a specialized center, the CIC bioGUNE, in Derio, Spain. A spokeswoman for the University of Barcelona says that they sent them in December 2022 and the three organizations received the results in March 2023. Four months later, in July, the legal departments at the three institutions finally informed the 4141 laboratory workers that the Creutzfeldt-Jakob disease samples were potentially infectious, as feared. “You can debate whether we have been quick [in our response] or not, but we have been transparent. We are [part of] three institutions that had to agree, and we have acted as guarantors,” says Capellá. A similar situation also occurred in France; following the death of a researcher from Creutzfeldt-Jakob in 2019 and the discovery of another suspected case, all public laboratories investigating prion diseases decided to temporarily close in July 2021 to review their protocols.

Laboratory 4141 was not equipped to handle high biohazard samples. It did not even have a biosafety hood. At the end of 2018, the CIBER public consortium signed an agreement so that the group could work with these dangerous samples at the high-security laboratory of the Animal Health Research Center (CReSA) in Bellaterra, Spain, near Barcelona. According to the sources we consulted, there was no reason to have the contaminated material in laboratory 4141, beyond saving time during experiments, since the CReSA bunker is 30 kilometers (about 19 miles) away and required waiting one’s turn to use. Isidre Ferrer, the head of the facility at the time, who has since retired, prefers not to comment on the case until the internal investigation is completed, but he emphasizes that he was unaware of the existence of these dangerous samples.

The IDIBELL director recalls that the deceased scientist was “a promising and brilliant researcher.” From 2013 to 2017, he worked at the University Medical Center of Göttingen (Germany) under neurologist Inga Zerr, a leading international expert in Creutzfeldt-Jakob disease. Physician Margarita Blázquez, who manages the CIBER public consortium, notes that the disease’s incubation period can last several years, so, if the deceased researcher really had it, he also could have become infected with it in Germany or at another of his previous laboratories. This newspaper has tried to contact the scientist’s widow via email but has not received a response. She asked to be discharged shortly after her husband did. The three institutions are now investigating whether the couple handled the dangerous samples without authorization in lab 4141. A third person affiliated with CIBER, a member of the now-deceased biochemist’s research group, worked with potentially infectious Creutzfeldt-Jakob samples without being informed that they were infectious.

The security office of the University of Barcelona believes that the samples would only have been a problem in the case of accidental inoculation or ingestion while handling them. But internal documents confirm the alarm the situation has caused on campus. “The laboratory technicians and investigators express their enormous concern about the fact that, so far, it has not been possible to determine the origin of the doctor’s illness. They are left to worry about whether they may suffer the same fate in a few years’ time as a result of uncontrolled contamination that may have been created in the laboratory,” according to the minutes of a December 22, 2020, meeting between workers and Carles Solsona, the director of the Department of Pathology at the University of Barcelona. “This fear causes them to suffer a state of permanent anguish, causing insomnia and irritability.”

The IDIBELL director sent a message to the center’s entire staff on the 11th, five days after EL PAÍS informed him that it was investigating the case. Gabriel Capellá then told his workers of “a very serious incident that became known on campus for the first time at the end of 2020.″ With “deep dismay,” Capellá announced the researcher’s death “due to a possible prion condition,” with “a possible iatrogenic [a disease acquired by contact with contaminated materials during a medical procedure].” The director also reported finding “potentially dangerous samples” in a freezer. “Our priority is to ensure that this situation is handled rigorously and transparently to limit the damage to the reputation of our institutions,” he said.

Do you have more information about this case or other similar ones? You can write to us at mansede@elpais.es.

https://english.elpais.com/science-tech/2023-10-20/an-investigation-has-been-opened-into-the-death-of-a-scientist-who-was-studying-a-transmissible-and-deadly-disease-in-spain.html

Friendly fire, pass it forward, they call it iatrogenic cjd, or what i call 'tse prion poker', are you all in $$$

all iatrogenic cjd is, is sporadic cjd, before the iatrogenic event is discovered, traced back, proven, documented, put into the academic domain, and then finally the public domain, this very seldom happens, thus problem solved, it's all sporadic cjd...

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

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

Jacqueline Mikol1 · Jérôme Delmotte1 · Dolorès Jouy1 · Elodie Vaysset1 · Charmaine Bastian1 · Jean‑Philippe Deslys1 ·

Emmanuel Comoy1 Received: 10 July 2020 / Revised: 8 September 2020 / Accepted: 25 September 2020 / Published online: 6 October 2020 © The Author(s) 2020

Non-human primates appeared as the closest model to study human iatrogenic prion diseases [14]: we report here the consequences of variant Creutzfeldt–Jakob disease/bovine spongiform encephalopathy (vCJD/BSE) inoculation in a cynomolgus macaque finger, with the demonstration of an original mode of propagation and the practical risk for professional exposure.

The distal right middle finger handpad of a 4-year-old macaque was incised on both lateral sides to induce local inflammation, and then injected with the equivalent of 10 mg of a BSE, orally challenged macaque brain [18]. After an 18 months period of finger clumsiness, the clinical disease (behaviour abnormalities, fear, hyperesthesia, gait disturbances, shaking) began 7.5 years after inoculation and euthanasia took place 2 months later for welfare reasons. Motor conduction velocity of the right median nerve was reduced to one-third of the left counterpart and sensory potential was not detected.

Histological and biochemical studies were performed as previously described. All the elements of the triad were present [7–9]: spongiform change was moderate in neocortex, striatum, brain stem, mild in spinal cord but severe in thalamus and cerebellum; neuronal loss was globally moderate, but severe in cerebellum and sacral spinal cord (vacuolated neurons); gliosis was severe in thalamus, cerebellum and brain stem and moderate elsewhere (Supplementary Fig. 1). ELISA and western blot (WB) showed the expected accumulation of PrPres with BSE glycophoretic pattern at all levels of brain and spinal cord (Supplementary Fig. 2).

In the brain, PrPd deposits were laminar into the cortical deep layers, massive into thalamus, basal ganglia, cerebellum, and brain stem. In spinal cord, PrPd was symmetrically distributed, intense in the Substantia gelatinosa and nucleus dorsal of Clarke while decreased at sacral level. Deposits were diverse into the whole CNS: synaptic, perineuronal, reticular aggregates, mini-plaques, plaques, and incomplete florid plaques. The retinal plexiform layers were labelled (Supplementary Fig. 1i). There were no amyloid or tau deposits.

Unusual PrPd deposits were observed along dendrites, short and long axons, neuritic threads tracing fne networks of straight lines or like strings of pearls (Supplementary Fig. 3). They were present into deep neocortex, basal ganglia, and motoneurons. Such long processes are not frequent but have been reported in human [13] and experimental studies [10, 22]. PrPd deposits were also noted as very mild into striato-pallidal projections, both limbs of internal capsule and fornix (Supplementary Fig. 3). The presence of PrPd in white matter has been reported (Supplementary text 4).

Peripherally, the expected PrPd was undetectable in lymphoid organs, including spleen, through biochemical or immunohistochemical analyses, while prion replication was detected in the peripheral nervous system (PNS): PrPd staining was visualized in many dorsal root ganglia (DRG) but only in nerves innervating the forelimb site of injection (median and ulnar nerves). At the cellular level, PrPd was limited to ganglia and satellite cells in DRG and Schwann cells (Scs) all along nerves whereas axons were never labelled (Fig. 1). Previously, using postmortem immunohistochemical studies (listed in Supplementary text 5), PrPd has been shown in peripheral nervous system in all forms of human neuropathies, albeit more frequently in vCJD, mostly in posterior root nerve fbres at adaxonal location and/or in ganglion and satellite cells. The restricted amount of PrPd was repeatedly underlined but, recently, prion RTQuiC was positive in all nerves examined [2]. PrPd has also been described, frst in scrapie [17] then in BSE, as limited “adaxonal deposits” or/and Sc deposits, with or without DRG cell involvement (review in [4] and Supplementary text 6). Previous studies of the mode of propagation of PrPd have reported variable observations and analyses depending on strains, host species and genotype (Supplementary text 6); the authors discussed the role of the sensory route of trafficking of prions, the modifications of axonal transport, the centrifugal versus centripetal spread of PrPd .

After peripheral infection, accumulation of infectious agent is reputed to occur in lymphoid tissues before direct neuroinvasion [18, 19], even with very little apparent peripheral lymphoreticular deposition [6, 20]. Here, there is no apparent replication/amplification of vCJD/BSE agent in the lymphoid tissues of the exposed macaque. In this model, the neural contamination occurred directly in the highly innervated finger while neuroinvasion appears to occur in Scs along the median nerve to the DRG, with the appearance of the classical labelling of ganglion cells which indicates the onset of the first level of neuronal infection. This model provides direct evidence of the hypothesis of a sequential infection of Scs from the periphery to the CNS, followed by a secondary diffusion into the spinal cord, as already considered by our group [15] and others [1, 3, 11, 12, 21]. It is to note that studies based on intra-sciatic nerve injections in hamsters [16] and transgenic mice [12] had established a rate of transport of infectivity of, respectively, 0.5–2 mm and 0.7 mm per day. This key role of Scs could explain both the low speed of propagation and the discrepancy between the paucity of PrPd into the distal part of the sensory nerves followed by the positivity of DRG, satellite cells and proximal roots.

In conclusion, we have observed that the exposure of a primate to vCJD/BSE through a distal finger lesion induces, after more than 7.5 years of silent incubation, a massive deposit of PrPd , strictly restricted to the nervous system and the eye.

Our data suggest a new type of pure unique peripheral nervous contamination in which the Scs would have a major role in the mode of centripetal progression of PrPd in the peripheral nervous system. Moreover, considering the fact that, recently, “a variant CJD diagnosed 7.5 years after occupational exposure” (cryomicrotomy) in a technician was observed [5], this experimental case report supports the risk linked to professional exposure and reinforces the necessity of adequate measures of prevention.

https://link.springer.com/content/pdf/10.1007/s00401-020-02231-w.pdf

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.

By Hervé Morin

Creutzfeldt-Jakob disease killed a few days ago a retired research technician from the National Research Institute for Agriculture, Food and the Environment (Inrae), who had worked in Toulouse in contact of biological tissue infected with prions. This death sows consternation and concern in the scientific community working with these infectious agents. It follows the death, on June 17, 2019, of Emilie Jaumain, a 33-year-old laboratory technician, suffering from the same incurable neurodegenerative disease. The young woman is said to have contracted it in 2010, cutting herself while handling fragments of the brains of mice infected with prions, in another unit of INRAE, in Jouy-en-Josas.

Computer representation of part of a prion protein on a light micrograph of pyramidal nerve cells (neurons, in black) in the cerebellum of the brain. ALFRED PASIEKA / SCIENCE PHOTO LIBRARY

Regarding the retiree from Toulouse, it will be necessary to determine whether she was the victim of a genetic or sporadic form of Creutzfeldt-Jakob disease, if the disease may have been caused by the ingestion of meat contaminated by the agent of encephalopathy. bovine spongiform (BSE, also called mad cow disease) or, as in the case of Emilie Jaumain, if accidental occupational exposure can be claimed. Prion diseases are caused by proteins taking an aberrant conformation, which gives them the property of replicating to form aggregates that are deleterious for neurons. There are around 150 cases per year in France, resulting in fatal degeneration of the central nervous system.

https://www.lemonde.fr/sciences/article/2021/11/30/second-deces-en-france-dans-un-laboratoire-travaillant-sur-les-prions_6104124_1650684.html

Temporary suspension of work on prions in French public research laboratories

PRESS RELEASE - The general directorates of ANSES, CEA, CNRS, INRAE and Inserm, have decided jointly and in agreement with the Ministry of Higher Education, Research and Innovation to suspend as a precaution all their research and experimentation work relating to prion diseases, for a period of three months.

This precautionary measure is motivated by the knowledge of a possible new case of a person suffering from Creutzfeldt-Jakob disease and who worked in a laboratory for research on prions.

Posted on July 27, 2021

The suspension period put in place as of this day will make it possible to study the possibility of a link between the observed case and the person's former professional activity and to adapt, if necessary, the preventive measures in force in the research laboratories.

The person with Creutzfeldt-Jakob disease (CJD)1, whose form is not yet known, is a retired INRAE agent. This could be the second case of infectious CJD affecting a scientist who worked on prions, after that of an assistant engineer who died of the disease in 2019, and who was injured in 2010 during of an experiment.

Following this death, a general inspection mission was launched in July 2019 by the ministries of research and agriculture with French laboratories handling prions. Submitted in October 2020, the report concluded on the regulatory compliance of the laboratories visited as well as the presence of a risk control culture within the research teams.

Research around prion proteins, with high public health issues, allows major advances in the understanding of the functioning of these infectious pathogens, and contributes to results that are transferable to other related degenerative diseases such as Alzheimer's and Alzheimer's diseases. Parkinson's.

At the level of each establishment, regular and transparent information will be provided to all the working communities concerned by this measure.

1 The disease Creutzfeldt-Jakob disease (CJD) is one of prion diseases - still called encephalopathies subacute spongiform transmitted(TSE) - of diseases rare, characterized by a degeneration rapid and fatal the system nervous central. They are caused by the accumulation in the brain of a normally expressed protein but poorly conformed - the prion protein - which leads to the formation of deleterious aggregates for neurons. For now , no treatment will allow to change the course of these diseases. It can be of origin sporadic , form the most frequent , original genetic or finally to form infectious following a contamination.

https://www.inserm.fr/information-en-sante/dossiers-information/maladies-prions-maladie-creutzfeldt-jakob

https://www.inrae.fr/actualites/suspension-provisoire-travaux-prions-laboratoires-recherche-publics-francais

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

By Barbara CasassusJul. 28, 2021 , 4:35 AM

PARIS—Five public research institutions in France have imposed a 3-month moratorium on the study of prions—a class of misfolding, infectious proteins that cause fatal brain diseases—after a retired lab worker who handled prions in the past was diagnosed with Creutzfeldt-Jakob disease (CJD), the most common prion disease in humans. An investigation is underway to find out whether the patient, who worked at a lab run by the National Research Institute for Agriculture, Food and Environment (INRAE), contracted the disease on the job.

If so, it would be the second such case in France in the past few years. In June 2019, an INRAE lab worker named Émilie Jaumain died at age 33, 10 years after pricking her thumb during an experiment with prion-infected mice. Her family is now suing INRAE for manslaughter and endangering life; her illness had already led to tightened safety measures at French prion labs.

The aim of the moratorium, which affects nine labs, is to “study the possibility of a link with the [new patient’s] former professional activity and if necessary to adapt the preventative measures in force in research laboratories,” according to a joint press release issued by the five institutions yesterday.

“This is the right way to go in the circumstances,” says Ronald Melki, a structural biologist at a prion lab jointly operated by the French national research agency CNRS and the French Alternative Energies and Atomic Energy Commission (CEA). “It is always wise to ask questions about the whole working process when something goes wrong.” "The occurrence of these harsh diseases in two of our scientific colleagues clearly affects the whole prion community, which is a small 'familial' community of less than 1000 people worldwide," Emmanuel Comoy, deputy director of CEA's Unit of Prion Disorders and Related Infectious Agents, writes in an email to Science. Although prion research already has strict safety protocols, "it necessarily reinforces the awareness of the risk linked to these infectious agents," he says.

In Jaumain’s case, there is little doubt she was infected on the job, according to a paper published in The New England Journal of Medicine (NEJM) in 2020. She had variant CJD (vCJD), a form typically caused by eating beef contaminated with bovine spongiform encephalopathy (BSE), or mad cow disease. But Europe’s BSE outbreak ended after 2000 and vCJD virtually disappeared; the chance that someone of Jaumain’s age in France would contract food-borne vCJD is “negligible or non-existent,” according to the paper.

A scientist with inside knowledge says the new patient, a woman who worked at INRAE’s Host-Pathogen Interactions and Immunity group in Toulouse, is still alive. French authorities were apparently alerted to her diagnosis late last week. The press release suggests it’s not yet clear whether the new case is vCJD or “classic” CJD, which is not known to be caused by prions from animals. Classic CJD strikes an estimated one person per million. Some 80% of cases are sporadic, meaning they have no known cause, but others are genetic or contracted from infected human tissues during transplantations. The two types of CJD can only be distinguished through a postmortem examination of brain tissue.

Lab infections are known to occur with many pathogens, but exposure to CJD-causing prions is unusually risky because there are no vaccines or treatments and the condition is universally fatal. And whereas most infections reveal themselves within days or weeks, CJD’s average incubation period is about 10 years.

For Jaumain, who worked at INRAE’s Molecular Virology and Immunology Unit in Jouy-en-Josas, outside Paris, that long period of uncertainty began on 31 May 2010, when she stabbed her left thumb with a curved forceps while cleaning a cryostat—a machine that can cut tissues at very low temperatures—that she used to slice brain sections from transgenic mice infected with a sheep-adapted form of BSE. She pierced two layers of latex gloves and drew blood. “Émilie started worrying about the accident as soon as it had happened, and mentioned it to every doctor she saw,” says her widower, Armel Houel.

In November 2017, Jaumain developed a burning pain in her right shoulder and neck that worsened and spread to the right half of her body over the following 6 months, according to the NEJM paper. In January 2019, she became depressed and anxious, suffering memory impairment and hallucinations. “It was a descent into hell,” Houel says. She was diagnosed with “probable vCJD” in mid-March of that year and died 3 months later. A postmortem confirmed the diagnosis.

“The occurrence of these harsh diseases in two of our scientific colleagues clearly affects the whole prion community.” Emmanuel Comoy, French Alternative Energies and Atomic Energy Commission

INRAE only recently admitted the likely link between Jaumain’s illness and the accident. “We recognize, without ambiguity, the hypothesis of a correlation between Emilie Jaumain-Houel’s accident … and her infection with vCJD,” INRAE chair and CEO Philippe Mauguin wrote in a 24 June letter to an association created by friends and colleagues to publicize Jaumain’s case and lobby for improvements in lab safety. (Science has obtained a copy of the letter, which has not been made public.)

Jaumain’s family has filed both criminal charges and an administrative suit against INRAE, alleging a range of problems at Jaumain’s lab. She had not been trained in handling dangerous prions or responding to accidents and did not wear both metal mesh and surgical gloves, as she was supposed to, says Julien Bensimhon, the family’s lawyer. The thumb should have been soaked in a bleach solution immediately, which did not happen, Bensimhon adds.

Independent reports by a company specializing in occupational safety and by government inspectors have found no safety violations at the lab; one of them said there was a “strong culture” of risk management. (Bensimhon calls the reports “biased.”)

The government inspectors’ report concluded that Jaumain’s accident was not unique, however. There had been at least 17 accidents among the 100 or so scientists and technicians in France working with prions in the previous decade, five of whom stabbed or cut themselves with contaminated syringes or blades. Another technician at the same lab had a fingerprick accident with prions in 2005, but has not developed vCJD symptoms so far, Bensimhon says. “It is shocking that no precautionary measures were taken then to ensure such an accident never happened again,” he says.

In Italy, too, the last person to die of vCJD, in 2016, was a lab worker with exposure to prion-infected brain tissue, according to last year’s NEJM paper, although an investigation did not find evidence of a lab accident. That patient and the lab they worked at have not been identified.

After Jaumain’s diagnosis, “We contacted all the research prion labs in France to suggest they check their safety procedures and remind staff about the importance of respecting them,” says Stéphane Haïk, a neuroscientist at the Paris Brain Institute at Pitié-Salpêtrière Hospital who helped diagnose Jaumain and is the corresponding author on the paper. Many labs tightened procedures, according to the government inspectors' report, for instance by introducing plastic scissors and scalpels, which are disposable and less sharp, and bite and cut-resistant gloves. A team of experts from the five research agencies is due to submit proposals for a guide to good practice in prion research to the French government at the end of this year.

The scientific community has long recognized that handling prions is dangerous and an occupational risk for neuropathologists, says neuropathologist Adriano Aguzzi of the University of Zurich. Aguzzi declined to comment on the French CJD cases, but told Science his lab never handles human or bovine prions for research purposes, only for diagnostics. “We conduct research only on mouse-adapted sheep prions, which have never been shown to be infectious to humans,” Aguzzi says. In a 2011 paper, his team reported that prions can spread through aerosols, at least in mice, which “may warrant re-thinking on prion biosafety guidelines in research and diagnostic laboratories,” they wrote. Aguzzi says he was “totally shocked” by the finding and introduced safety measures to prevent aerosol spread at his own lab, but the paper drew little attention elsewhere.

The moratorium will "obviously" cause delays in research, but given the very long incubation periods in prion diseases, the impact of a 3-month hiatus will be limited, Comoy says. His research team at CEA also works on other neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease, and will shift some of its efforts to those.

Although Jaumain’s diagnosis upset many in the field, it hasn't led to an exodus among researchers in France, Haïk says: “I know of only one person who resigned because they were so worried.”

With reporting by Martin Enserink.

Posted in: EuropeHealthScientific Community

doi:10.1126/science.abl6587

https://www.sciencemag.org/news/2021/07/france-issues-moratorium-prion-research-after-fatal-brain-disease-strikes-two-lab

Variant Creutzfeldt–Jakob Disease Diagnosed 7.5 Years after Occupational Exposure

Variant Creutzfeldt–Jakob disease was identified in a technician who had cut her thumb while handling brain sections of mice infected with adapted BSE 7.5 years earlier. The long incubation period was similar to that of the transfusion-transmitted form of the disease.

Variant Creutzfeldt–Jakob Disease Diagnosed 7.5 Years after Occupational Exposure

TO THE EDITOR:

We report a case of variant Creutzfeldt–Jakob disease (CJD) that was plausibly related to accidental occupational exposure in a technician who had handled murine samples contaminated with the agent that causes bovine spongiform encephalopathy (BSE) 7.5 years earlier.

In May 2010, when the patient was 24 years of age, she worked in a prion research laboratory, where she handled frozen sections of brain of transgenic mice that overexpressed the human prion protein with methionine at codon 129. The mice had been infected with a sheep-adapted form of BSE. During this process, she stabbed her thumb through a double pair of latex gloves with the sharp ends of a curved forceps used to handle the samples. Bleeding was noted at the puncture site.

In November 2017, she began having burning pain in the right shoulder and neck. The pain worsened and spread to the right half of her body during the following 6 months. In November 2018, an examination of a sample of cerebrospinal fluid (CSF) obtained from the patient was normal. Magnetic resonance imaging (MRI) of the brain showed a slight increase in the fluid-attenuated inversion recovery (FLAIR) signal in the caudates and thalami (Fig. S1A and S1B in the Supplementary Appendix, available with the full text of this letter at NEJM.org). In January 2019, she became depressed and anxious and had memory impairment and visual hallucinations. There was hypertonia on the right side of her body. At that time, an analysis of CSF for 14-3-3 protein was negative. In March 2019, MRI showed an increased FLAIR signal in pulvinar and dorsomedial nuclei of thalami (Fig. S1C through S1E).

Figure 1.

Detection of Abnormal Prion Protein in Biologic Fluid Samples and Postmortem Findings.

The patient was found to be homozygous for methionine at codon 129 of the prion protein gene without mutation. An analysis of a sample of CSF on real-time quaking-induced conversion analysis was negative for a diagnosis of sporadic CJD. However, an analysis of plasma and CSF by means of protein misfolding cyclic amplification was positive for the diagnosis of variant CJD (Figure 1A and 1B). The patient died 19 months after the onset of symptoms. Neuropathological examination confirmed the diagnosis of variant CJD (Figure 1C and 1D). Western blot analysis showed the presence of type 2B protease-resistant prion protein in all sampled brain areas. The clinical characteristics of the patient and the postmortem neuropathological features were similar to those observed in 27 patients with variant CJD who had previously been reported in France.1 (Additional details are provided in the Supplementary Appendix.)

There are two potential explanations for this patient’s condition. Oral transmission from contaminated cattle products cannot be ruled out because the patient was born at the beginning of the French BSE outbreak in cattle. However, the last two patients who had confirmed variant CJD with methionine homozygosity at codon 129 in France and the United Kingdom died in 2014 and 2013, respectively, which makes oral transmission unlikely. In France, the risk of variant CJD in 2019 was negligible or nonexistent in the post-1969 birth cohort.2

Percutaneous exposure to prion-contaminated material is plausible in this patient, since the prion strain that she had handled was consistent with the development of variant CJD.3 The 7.5-year delay between the laboratory accident and her clinical symptoms is congruent with the incubation period in the transfusion-transmitted form of the disease. The ability of this strain to propagate through the peripheral route has been documented, and experimental studies with scrapie strains have shown that scarification and subcutaneous inoculation are effective routes.4,5 The last known Italian patient with variant CJD, who died in 2016, had had occupational contact with BSE-infected brain tissues, although subsequent investigation did not disclose a laboratory accident (Pocchiari M, Italian Registry of CJD: personal communication). Thus, the last two cases of variant CJD outside the United Kingdom have been associated with potential occupational exposure. Such cases highlight the need for improvements in the prevention of transmission of variant CJD and other prions that can affect humans in the laboratory and neurosurgery settings, as outlined in the Supplementary Appendix.

Jean-Philippe Brandel, M.D. Assistance Publique–Hôpitaux de Paris, Paris, France

M. Bustuchina Vlaicu, M.D. Groupe Hospitalier Nord-Essonne, Orsay, France

Audrey Culeux, B.Sc. INSERM Unité 1127, Paris, France

Maxime Belondrade, M.Sc. Daisy Bougard, Ph.D. Etablissement Français du Sang, Montpellier, France

Katarina Grznarova, Ph.D. Angeline Denouel, M.Sc. INSERM Unité 1127, Paris, France

Isabelle Plu, M.D. Elodie Bouaziz-Amar, Pharm.D., Ph.D. Danielle Seilhean, M.D., Ph.D. Assistance Publique–Hôpitaux de Paris, Paris, France

Michèle Levasseur, M.D. Groupe Hospitalier Nord-Essonne, Orsay, France

Stéphane Haïk, M.D., Ph.D. INSERM Unité 1127, Paris, France stephane.haik@upmc.fr

Supported by a grant (ANR-10-IAIHU-06) from Programme d’Investissements d’Avenir and Santé Publique France.

Disclosure forms provided by the authors are available with the full text of this letter at NEJM.org.

5 References

July 2, 2020

N Engl J Med 2020; 383:83-85

DOI: 10.1056/NEJMc2000687

Metrics

https://www.nejm.org/doi/full/10.1056/NEJMc2000687

34 year old Doctor Orthopedic Surgeon dies from CJD

Dr. Adam Thomas Dialectos

1987 - 2021

BORN

April 29, 1987

DIED

June 21, 2021

FUNERAL HOME

Bean Funeral Homes & Crematory Inc

1605 Rockland St

Reading, PA 19604

UPCOMING SERVICE

Visitation

Jun, 24 2021

9:00a.m. - 11:00a.m.

Saints Constantine & Helen Greek Orthodox Church

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On Monday June 21, 2021, Dr. Adam Thomas Dialectos, loving husband, father, son, brother, uncle, Nouno, friend at the age of 34. Adam was born on April 29, 1987 in Reading, PA to Athan and Gretchen Dialectos. Adam was a 2005 graduate of Governor Mifflin High School, before receiving his degree in Health Sciences from James Madison University in 2009. Adam attended Philadelphia College of Osteopathic Medicine for medical school and his subsequent residency in orthopedic surgery. Adam was completing his Spine Surgery Fellowship at New England Baptist Hospital in Boston, Massachusetts. On February 7, 2019 Adam married the love of his life and girlfriend of 12 years, Lindsey (Schuler) Dialectos. They brought a beautiful baby boy into this world on January 6, 2021, Athananosis Adam Dialectos. Adam’s passion in life was unceasingly seeking to help others, emphasized by his desire to be a surgeon— a decision he made in his early elementary years. Adam continued this love of medicine throughout his life, which led to his achieving of the Henrietta and Jack Avart Memorial Award in 2019, awarded to the Orthopedic surgery resident who exhibited unparalleled excellence in their field during the residency program. This passion to learn, teach and support was truly understood through the patients whose lives Adam touched. When it came to his patients and coworkers, there was never a job too small for Adam. Those who knew Adam saw his personality shine through in so many other aspects of his life. Adam loved traveling. Some of his most memorable trips were with his wife, and countless snowboard trips with his brother, family, and friends. Adam loved everyone he was around; he loved and was loved by so many. Adam was truly one in a million. Adam is survived by his loving wife, Lindsey, and their son, Athan Adam; His father and mother, Athan and Gretchen; His brother Jordan and sister-in-law Megan, and their daughter Livia, Adam’s Goddaughter. His sister, Rachel, and her significant other, Bo Wagner. Furthermore, Adam is survived by his Yiayia, Joanne Dialectos, wife of the late George Dialectos; his Pop Pop, Donald Harford, husband of the late Nancy Servent; his Aunt Angel and Uncle Scott Helm; his Aunt Kelly and Uncle Darrell Markley. Adam was preceded in death by his Aunt Maria and Uncle Bob Care. Funeral Service will be held at Saints Constantine & Helen Greek Orthodox Church, 1001 East Wyomissing Blvd. Reading on Thursday June 24th. Father Theodore Petrides and Father Thomas L. Pappalas will officiate. Interment will follow at Charles Evans Cemetery. The family will receive relatives and friends at Saints Constantine & Helen Greek Orthodox Church from 9:00am to 11:00am with services beginning at 11:00. In lieu of flowers, contributions may be made to the CJD Foundation at 3634 West Market Street Suite 110 Akron, Ohio 44333 or cjdfoundation.org in remembrance of Dr. Adam Dialectos. Donations may also be made to Saints Constantine & Helen Greek Orthodox Church. Bean Funeral Home, 1605 Rockland Street, Hampden Heights, is in charge of arrangements and online condolences may be made at www.beanfuneralhomes.com.

To plant trees in memory, please visit our Sympathy Store.

Published by Reading Eagle from Jun. 22 to Jun. 24, 2021.

https://www.legacy.com/us/obituaries/readingeagle/name/adam-dialectos-obituary?pid=199144663

Our sincere condolences to the Family and Friends of Dr. Adam Thomas Dialectos.

I can't help but ponder, as a Orthopedic Surgeon, Spine Surgery Fellowship, and what the good Doctors work curtailed, i can't help but think this is a potential case of iatrogenic CJD. surgery on humans, i would imagine cadavers as well.

all iatrogenic cjd is, is sporadic cjd, before the iatrogenic event is discovered, traced back, provern, documented, put into the academic domain, and then finally the public domain, this very seldom happens, thus problem solved, it's all sporadic cjd. ...terry

least we forget...

*** Transmission of Creutzfeldt-Jakob disease to a chimpanzee by electrodes contaminated during neurosurgery ***

Gibbs CJ Jr, Asher DM, Kobrine A, Amyx HL, Sulima MP, Gajdusek DC.

Laboratory of Central Nervous System Studies, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892. Stereotactic multicontact electrodes used to probe the cerebral cortex of a middle aged woman with progressive dementia were previously implicated in the accidental transmission of Creutzfeldt-Jakob disease (CJD) to two younger patients. The diagnoses of CJD have been confirmed for all three cases. More than two years after their last use in humans, after three cleanings and repeated sterilisation in ethanol and formaldehyde vapour, the electrodes were implanted in the cortex of a chimpanzee. Eighteen months later the animal became ill with CJD. This finding serves to re-emphasise the potential danger posed by reuse of instruments contaminated with the agents of spongiform encephalopathies, even after scrupulous attempts to clean them.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8006664&dopt=Abstract

Saturday, December 18, 2021

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

https://itseprion.blogspot.com/2021/12/direct-neural-transmission-of-vcjdbse.html

Tuesday, November 30, 2021

Second death in France in a laboratory working on prions

https://itseprion.blogspot.com/2021/11/second-death-in-france-in-laboratory.html

Second lab worker with deadly prion disease prompts research pause in France

A lab worker died of prion disease in 2019, nine years after a lab accident.

BETH MOLE - 7/29/2021, 5:16 PM

https://arstechnica.com/science/2021/07/second-lab-worker-with-deadly-prion-disease-prompts-research-pause-in-france/

A 2020 paper published in the New England Journal of Medicine left little doubt that Jaumain had been infected on the job. She had variant CJD, but since Europe’s ‘mad cow’ outbreak ended after 2000 and the disease virtually disappeared, the paper said it was virtually impossible for someone her age in France to contract food-borne vCJD.

Science also said two independent reports – one by government inspectors – had found no safety violations at the lab where Jaumain worked. The press release also noted that the inspectors concluded there was “the presence of a risk control culture within the research teams”. The Jaumain family’s lawyer called the neutrality of the reports into question, however.

At the same time, the government inspectors’ report also revealed that there had been at least 17 accidents among the 100 or so scientists and technicians in France working with prions in the previous decade, raising concerns about how effective this risk control culture is. Five of these occurred when workers “stabbed or cut themselves with contaminated syringes or blades”.

https://science.thewire.in/the-sciences/second-case-of-fatal-disease-prompts-french-moratorium-on-prion-research/

Wednesday, July 28, 2021

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

https://itseprion.blogspot.com/2021/07/france-issues-moratorium-on-prion.html

Wednesday, July 28, 2021

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

https://itseprion.blogspot.com/2021/07/france-issues-moratorium-on-prion.html

SATURDAY, AUGUST 01, 2020

Sporadic Creutzfeldt-Jakob Disease among Physicians, Germany, 1993–2018 high proportion of physicians with sCJD were surgeons

https://creutzfeldt-jakob-disease.blogspot.com/2020/08/

SUNDAY, JULY 19, 2020

Joseph J. Zubak Orthopaedic surgeon passed away Monday, July 6, 2020, Creutzfeldt-Jakob Disease (CJD)

https://creutzfeldt-jakob-disease.blogspot.com/2020/07/joseph-j-zubak-orthopaedic-surgeon.html

Variant Creutzfeldt–Jakob Disease Diagnosed 7.5 Years after Occupational Exposure

https://www.nejm.org/doi/full/10.1056/NEJMc2000687

https://www.nejm.org/doi/suppl/10.1056/NEJMc2000687/suppl_file/nejmc2000687_appendix.pdf

THURSDAY, JULY 02, 2020

Variant Creutzfeldt–Jakob Disease Diagnosed 7.5 Years after Occupational Exposure

https://vcjd.blogspot.com/2020/07/variant-creutzfeldtjakob-disease.html

Thursday, July 29, 2021

TSE PRION OCCUPATIONAL EXPOSURE VIA ANIMAL OR HUMAN, iatrogenic transmission, nvCJD or sCJD, what if?

https://itseprion.blogspot.com/2021/07/tse-prion-occupational-exposure-via.html

Chronic Wasting Disease CWD TSE Prion aka mad cow type disease in cervid Zoonosis Update

***> ''In particular the US data do not clearly exclude the possibility of human (sporadic or familial) TSE development due to consumption of venison. The Working Group thus recognizes a potential risk to consumers if a TSE would be present in European cervids.'' Scientific opinion on chronic wasting disease (II) <***

What if?

https://chronic-wasting-disease.blogspot.com/2019/12/chronic-wasting-disease-cwd-tse-prion.html

Friday, January 29, 2021

Scientists identify locations of early prion protein deposition in retina, what if?

https://itseprion.blogspot.com/2021/01/scientists-identify-locations-of-early.html

Saturday, January 23, 2021

Improved surveillance of surgical instruments reprocessing following the variant Creutzfeldt-Jakob disease crisis in England: findings from a 3-year survey

https://itseprion.blogspot.com/2021/01/improved-surveillance-of-surgical.html

https://creutzfeldt-jakob-disease.blogspot.com/2019/09/

FRIDAY, SEPTEMBER 06, 2019

Disinfection of Multi-Use Ocular Equipment for Ophthalmological Procedures: A Review of Clinical Effectiveness, Cost-Effectiveness, and Guidelines

https://creutzfeldt-jakob-disease.blogspot.com/2019/09/disinfection-of-multi-use-ocular.html

vpspr, sgss, sffi, TSE, an iatrogenic by-product of gss, ffi, familial type prion disease, what if ???

Greetings Friends, Neighbors, and Colleagues,

https://familialcjdtseprion.blogspot.com/2019/02/cwd-gss-tse-prion-spinal-cord-confucius.html

http://transmissiblespongiformencephalopathy.blogspot.com/2014/01/vpspr-sgss-sffi-tse-iatrogenic-by.html

Saturday, February 2, 2019

CWD GSS TSE PRION SPINAL CORD, Confucius Ponders, What if?

snip...

***> In particular the US data do not clearly exclude the possibility of human (sporadic or familial) TSE development due to consumption of venison. The Working Group thus recognizes a potential risk to consumers if a TSE would be present in European cervids.'' Scientific opinion on chronic wasting disease (II) <***

REVIEW

***> In conclusion, sensory symptoms and loss of reflexes in Gerstmann-Sträussler-Scheinker syndrome can be explained by neuropathological changes in the spinal cord. We conclude that the sensory symptoms and loss of lower limb reflexes in Gerstmann-Sträussler-Scheinker syndrome is due to pathology in the caudal spinal cord. <***

***> The clinical and pathological presentation in macaques was mostly atypical, with a strong emphasis on spinal cord pathology.<***

***> 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. <***

***> All animals have variable signs of prion neuropathology in spinal cords and brains and by supersensitive IHC, reaction was detected in spinal cord segments of all animals.<***

Thursday, March 8, 2018

Familial human prion diseases associated with prion protein mutations Y226X and G131V are transmissible to transgenic mice expressing human prion protein

https://familialcjdtseprion.blogspot.com/2018/03/familial-human-prion-diseases.html

THURSDAY, FEBRUARY 15, 2018

Iatrogenic Creutzfeldt-Jakob disease with Amyloid-β pathology: an international study

http://creutzfeldt-jakob-disease.blogspot.com/2018/02/iatrogenic-creutzfeldt-jakob-disease.html

FRIDAY, JANUARY 10, 2014

vpspr, sgss, sffi, TSE, an iatrogenic by-product of gss, ffi, familial type prion disease, what it ???

Greetings Friends, Neighbors, and Colleagues,

vpspr, sgss, sffi, TSE, an iatrogenic by-product of gss, ffi, familial type prion disease, what it ???

Confucius is confused again.

I was just sitting and thinking about why there is no genetic link to some of these TSE prion sGSS, sFFi, and it’s really been working on my brain, and then it hit me today.

what if, vpspr, sgss, sffi, TSE prion disease, was a by-product from iatrogenic gss, ffi, familial type prion disease ???

it could explain the cases of no genetic link to the gss, ffi, familial type prion disease, to the family.

sporadic and familial is a red herring, in my opinion, and underestimation is spot on, due to the crude prehistoric diagnostic procedures and criteria and definition of a prion disease.

I say again, what if, iatrogenic, what if, with all these neurological disorders, with a common denominator that is increasingly showing up in the picture, called the prion.

I urge all scientist to come together here, with this as the utmost of importance about all these neurological disease that are increasingly showing up as a prion mechanism, to put on the front burners, the IATROGENIC aspect and the potential of transmission there from, with diseases/disease???

in question, by definition, could they be a Transmissible Spongiform Encephalopathy TSE prion type disease, and if so, what are the iatrogenic chances of transmission?

this is very important, and should be at the forefront of research, and if proven, could be a monumental breakthrough in science and battle against the spreading of these disease/diseases.

http://transmissiblespongiformencephalopathy.blogspot.com/2014/01/vpspr-sgss-sffi-tse-iatrogenic-by.html

Friday, January 10, 2014

vpspr, sgss, sffi, TSE, an iatrogenic by-product of gss, ffi, familial type prion disease, what it ???

Greetings Friends, Neighbors, and Colleagues,

http://transmissiblespongiformencephalopathy.blogspot.com/2014/01/vpspr-sgss-sffi-tse-iatrogenic-by.html

http://alpha-synuclein.blogspot.com/

Sunday, October 27, 2013

A Kiss of a Prion: New Implications for Oral Transmissibility

http://transmissiblespongiformencephalopathy.blogspot.com/2013/10/a-kiss-of-prion-new-implications-for.html

***The occurrence of contact cases raises the possibility that transmission in families may be effected by an unusually virulent strain of the agent.

snip...see full text here;

http://web.archive.org/web/20050425210551/http://www.bseinquiry.gov.uk/files/mb/m26/tab01.pdf

snip...see full text;

https://familialcjdtseprion.blogspot.com/

Title: Transmission of scrapie prions to primate after an extended silent incubation period)

*** In complement to the recent demonstration that humanized mice are susceptible to scrapie, we report here the first observation of direct transmission of a natural classical scrapie isolate to a macaque after a 10-year incubation period. Neuropathologic examination revealed all of the features of a prion disease: spongiform change, neuronal loss, and accumulation of PrPres throughout the CNS.

*** This observation strengthens the questioning of the harmlessness of scrapie to humans, at a time when protective measures for human and animal health are being dismantled and reduced as c-BSE is considered controlled and being eradicated.

*** Our results underscore the importance of precautionary and protective measures and the necessity for long-term experimental transmission studies to assess the zoonotic potential of other animal prion strains.

http://www.ars.usda.gov/research/publications/publications.htm?SEQ_NO_115=313160

***Transmission data also revealed that several scrapie prions propagate in HuPrP-Tg mice with efﬁciency comparable to that of cattle BSE. While the efﬁciency of transmission at primary passage was low, subsequent passages resulted in a highly virulent prion disease in both Met129 and Val129 mice.

***Transmission of the different scrapie isolates in these mice leads to the emergence of prion strain phenotypes that showed similar characteristics to those displayed by MM1 or VV2 sCJD prion.

***These results demonstrate that scrapie prions have a zoonotic potential and raise new questions about the possible link between animal and human prions.

http://www.tandfonline.com/doi/abs/10.1080/19336896.2016.1163048?journalCode=kprn20

***Moreover, sporadic disease has never been observed in breeding colonies or primate research laboratories, most notably among hundreds of animals over several decades of study at the National Institutes of Health25, and in nearly twenty older animals continuously housed in our own facility.***

Even if the prevailing view is that sporadic CJD is due to the spontaneous formation of CJD prions, it remains possible that its apparent sporadic nature may, at least in part, result from our limited capacity to identify an environmental origin.

https://www.nature.com/articles/srep11573

https://www.ars.usda.gov/research/publications/publication/?seqNo115=361032

1: J Infect Dis 1980 Aug;142(2):205-8

Oral transmission of kuru, Creutzfeldt-Jakob disease, and scrapie to nonhuman primates.

Gibbs CJ Jr, Amyx HL, Bacote A, Masters CL, Gajdusek DC.

Kuru and Creutzfeldt-Jakob disease of humans and scrapie disease of sheep and goats were transmitted to squirrel monkeys (Saimiri sciureus) that were exposed to the infectious agents only by their nonforced consumption of known infectious tissues. The asymptomatic incubation period in the one monkey exposed to the virus of kuru was 36 months; that in the two monkeys exposed to the virus of Creutzfeldt-Jakob disease was 23 and 27 months, respectively; and that in the two monkeys exposed to the virus of scrapie was 25 and 32 months, respectively. Careful physical examination of the buccal cavities of all of the monkeys failed to reveal signs or oral lesions. One additional monkey similarly exposed to kuru has remained asymptomatic during the 39 months that it has been under observation.

snip...

The successful transmission of kuru, Creutzfeldt-Jakob disease, and scrapie by natural feeding to squirrel monkeys that we have reported provides further grounds for concern that scrapie-infected meat may occasionally give rise in humans to Creutzfeldt-Jakob disease.

PMID: 6997404

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6997404&dopt=Abstract

Recently the question has again been brought up as to whether scrapie is transmissible to man. This has followed reports that the disease has been transmitted to primates. One particularly lurid speculation (Gajdusek 1977) conjectures that the agents of scrapie, kuru, Creutzfeldt-Jakob disease and transmissible encephalopathy of mink are varieties of a single "virus". The U.S. Department of Agriculture concluded that it could "no longer justify or permit scrapie-blood line and scrapie-exposed sheep and goats to be processed for human or animal food at slaughter or rendering plants" (ARC 84/77)" The problem is emphasised by the finding that some strains of scrapie produce lesions identical to the once which characterise the human dementias"

Whether true or not. the hypothesis that these agents might be transmissible to man raises two considerations. First, the safety of laboratory personnel requires prompt attention. Second, action such as the "scorched meat" policy of USDA makes the solution of the acrapie problem urgent if the sheep industry is not to suffer grievously.

snip...

76/10.12/4.6

http://web.archive.org/web/20010305223125/www.bseinquiry.gov.uk/files/yb/1976/10/12004001.pdf

Nature. 1972 Mar 10;236(5341):73-4.

Transmission of scrapie to the cynomolgus monkey (Macaca fascicularis).

Gibbs CJ Jr, Gajdusek DC.

Nature 236, 73 - 74 (10 March 1972); doi:10.1038/236073a0

Transmission of Scrapie to the Cynomolgus Monkey (Macaca fascicularis)

C. J. GIBBS jun. & D. C. GAJDUSEK

National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, Maryland

SCRAPIE has been transmitted to the cynomolgus, or crab-eating, monkey (Macaca fascicularis) with an incubation period of more than 5 yr from the time of intracerebral inoculation of scrapie-infected mouse brain. The animal developed a chronic central nervous system degeneration, with ataxia, tremor and myoclonus with associated severe scrapie-like pathology of intensive astroglial hypertrophy and proliferation, neuronal vacuolation and status spongiosus of grey matter. The strain of scrapie virus used was the eighth passage in Swiss mice (NIH) of a Compton strain of scrapie obtained as ninth intracerebral passage of the agent in goat brain, from Dr R. L. Chandler (ARC, Compton, Berkshire).

http://www.nature.com/nature/journal/v236/n5341/abs/236073a0.html

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.

https://www.ars.usda.gov/research/publications/publication/?seqNo115=353091

https://www.ars.usda.gov/research/project/?accnNo=432011&fy=2017

https://www.ars.usda.gov/research/publications/publication/?seqNo115=337105

https://www.ars.usda.gov/research/publications/publication/?seqNo115=326166

CONFIDENTIAL

EXPERIMENTAL PORCINE SPONGIFORM ENCEPHALOPATHY

LINE TO TAKE

3. If questions on pharmaceuticals are raised at the Press conference, the suggested line to take is as follows:-

"There are no medicinal products licensed for use on the market which make use of UK-derived porcine tissues with which any hypothetical “high risk" ‘might be associated. The results of the recent experimental work at the CSM will be carefully examined by the CSM‘s Working Group on spongiform encephalopathy at its next meeting.

DO Hagger RM 1533 MT Ext 3201

http://web.archive.org/web/20030822054419/www.bseinquiry.gov.uk/files/yb/1990/09/21009001.pdf

While this clearly is a cause for concern we should not jump to the conclusion that this means that pigs will necessarily be infected by bone and meat meal fed by the oral route as is the case with cattle. ...

http://web.archive.org/web/20031026000118/www.bseinquiry.gov.uk/files/yb/1990/08/23004001.pdf

we cannot rule out the possibility that unrecognised subclinical spongiform encephalopathy could be present in British pigs though there is no evidence for this: only with parenteral/implantable pharmaceuticals/devices is the theoretical risk to humans of sufficient concern to consider any action.

http://web.archive.org/web/20030822031154/www.bseinquiry.gov.uk/files/yb/1990/09/10007001.pdf

May I, at the outset, reiterate that we should avoid dissemination of papers relating to this experimental finding to prevent premature release of the information. ...

http://web.archive.org/web/20030822052332/www.bseinquiry.gov.uk/files/yb/1990/09/11005001.pdf

3. It is particularly important that this information is not passed outside the Department, until Ministers have decided how they wish it to be handled. ...

http://web.archive.org/web/20030822052438/www.bseinquiry.gov.uk/files/yb/1990/09/12002001.pdf

But it would be easier for us if pharmaceuticals/devices are not directly mentioned at all. ...

http://web.archive.org/web/20030518170213/www.bseinquiry.gov.uk/files/yb/1990/09/13004001.pdf

Our records show that while some use is made of porcine materials in medicinal products, the only products which would appear to be in a hypothetically ''higher risk'' area are the adrenocorticotrophic hormone for which the source material comes from outside the United Kingdom, namely America China Sweden France and Germany. The products are manufactured by Ferring and Armour. A further product, ''Zenoderm Corium implant'' manufactured by Ethicon, makes use of porcine skin - which is not considered to be a ''high risk'' tissue, but one of its uses is described in the data sheet as ''in dural replacement''. This product is sourced from the United Kingdom.....

http://web.archive.org/web/20030822054419/www.bseinquiry.gov.uk/files/yb/1990/09/21009001.pdf

Fortuitous generation of a zoonotic cervid prion strain

Manuel Camacho, Xu Qi, Liuting Qing, Sydney Smith, Jieji Hu, Wanyun Tao, Ignazio Cali, Qingzhong Kong. Department of Pathology, Case Western Reserve University, Cleveland, USA

Funded by: NIH Grant number: R01NS052319, R01NS088604, R01NS109532

PRION 2023 CONTINUED;

https://prion2023.org/wp-content/uploads/2023/10/Meeting-book-final-version2.pdf

***> Currently, there is scientific evidence to suggest that CWD has zoonotic potential; however, no confirmed cases of CWD have been found in humans.

PART 2. TPWD CHAPTER 65. DIVISION 1. CWD

31 TAC §§65.82, 65.85, 65.88

***> Currently, there is scientific evidence to suggest that CWD has zoonotic potential; however, no confirmed cases of CWD have been found in humans.

https://www.sos.texas.gov/texreg/archive/June302023/Adopted%20Rules/31.NATURAL%20RESOURCES%20AND%20CONSERVATION.html#57

17 DETECTION OF CHRONIC WASTING DISEASE PRIONS IN PROCESSED MEATS.

Rebeca Benavente1, Francisca Bravo1,2, Paulina Soto1,2, J. Hunter Reed3, Mitch Lockwood3, Rodrigo Morales1,2

Abstract

***> Our results show positive prion detection in all products.

***> 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.

***> 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.

***> Epidemiologic surveillance of prion disease among cervid hunters and people likely to have consumed venison contaminated with chronic wasting disease

=====

https://intcwdsympo.files.wordpress.com/2023/06/final-agenda-with-abstracts.pdf?force_download=true

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

Aims: Chronic wasting disease (CWD), a prion disease of cervids, spreads efficiently among wild and farmed animals. Potential transmission to humans of CWD is a growing concern due to its increasing prevalence. Here, we aimed to determine the zoonotic potential of CWD using a mouse model for human prion diseases.

Material and Methods: Transgenic mice overexpressing human PrPChomozygous for methionine at codon 129 (tg650) were inoculated intracerebrally with brain homogenates of white-tailed deer infected with Wisc-1/CWD1 or 116AG CWD strains. Mice were monitored for clinical signs and were euthanized at terminal disease. Brains were tested by RT-QuIC, western blot upon PK digestion, and immunohistochemistry; fecal homogenates were analyzed by RT-QuIC. Brain/spinal cord and fecal homogenates of CWD-inoculated tg650 mice were inoculated into tg650 mice or bank voles. Brain homogenates of bank voles inoculated with fecal homogenates of CWD-infected tg650 mice were used for second passage in bank voles.

Results: Here, we provide the strongest evidence supporting the zoonotic potential of CWD prions, and their possible phenotype in humans. Inoculation of mice expressing human PrPCwith deer CWD isolates (strains Wisc-1 and 116AG) resulted in atypical clinical manifestations in > 75% of the mice, with myoclonus as leading clinical sign. Most of tg650brain homogenates were positive for seeding activity in RT-QuIC. Clinical disease and presentation was transmissible to tg650 mice and bank voles. Intriguingly, protease-resistant PrP in the brain of tg650 mice resembled that found in a familial human prion disease and was transmissible upon passage. Abnormal PrP aggregates upon infection with Wisc-1 were detectable in thalamus, hypothalamus, and midbrain/pons regions.

Unprecedented in human prion disease, feces of CWD-inoculated tg650 mice harbored prion seeding activity and infectious prions, as shown by inoculation of bank voles and tg650 with fecal homogenates.

Conclusions: This is the first evidence that CWD can infect humans and cause disease with a distinctive clinical presentation, signature, and tropism, which might be transmissible between humans while current diagnostic assays might fail to detect it. These findings have major implications for public health and CWD-management.

https://www.tandfonline.com/doi/full/10.1080/19336896.2022.2091286

PLoS One. 2020; 15(8): e0237410. Published online 2020 Aug 20. doi: 10.1371/journal.pone.0237410 PMCID: PMC7446902 PMID: 32817706

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

Abstract

While low-dose exposures to prions of brain or saliva origin prolonged the time from inoculation to first detection of infection, once infection was established, we observed no differences in disease pathogenesis. These studies suggest that the CWD minimum infectious dose approximates 100 to 300 ng CWD-positive brain (or saliva equivalent), and that CWD infection appears to conform more with a threshold than a cumulative dose dynamic.

snip...

The results demonstrate: (a) that the minimum CWD oral infectious dose is vastly lower than historical studies used to establish infection; (b) that a direct relationship exists between dose and incubation time to first prion replication detection in tonsils, irrespective of genotype; (c) that a difference was not discernible between brain vs. saliva source prions in ability to establish infection or in resultant disease course; and (d) that the CWD infection process appears to conform more to a threshold dose than an accumulative dose dynamic.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7446902/

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

Original Paper Open access Published: 22 August 2022 volume 144, pages767–784 (2022)

HIGHLIGHTS OF THIS STUDY

================================

Our results suggest that CWD might infect humans, although the transmission barrier is likely higher compared to zoonotic transmission of cattle prions. Notably, our data suggest a different clinical presentation, prion signature, and tissue tropism, which causes challenges for detection by current diagnostic assays. Furthermore, the presence of infectious prions in feces is concerning because if this occurs in humans, it is a source for human-to-human transmission. These findings have strong implications for public health and CWD management.

In this study, we evaluated the zoonotic potential of CWD using a transgenic mouse model overexpressing human M129-PrPC (tg650[12]). We inoculated tg650 mice intracerebrally with two deer CWD isolates, Wisc-1 and 116AG [22, 23, 27, 29]. We demonstrate that this transgenic line was susceptible to infection with CWD prions and displayed a distinct leading clinical sign, an atypical PrPSc signature and unusual fecal shedding of infectious prions. Importantly, these prions generated by the human PrP transgenic mice were transmissible upon passage. Our results are the first evidence of a zoonotic risk of CWD when using one of the most common CWD strains, Wisc-1/CWD1 for infection. We demonstrated in a human transgenic mouse model that the species barrier for transmission of CWD to humans is not absolute. The fact that its signature was not typical raises the questions whether CWD would manifest in humans as a subclinical infection, whether it would arise through direct or indirect transmission including an intermediate host, or a silent to uncovered human-to-human transmission, and whether current detection techniques will be suffcient to unveil its presence.

Our findings strongly suggest that CWD should be regarded as an actual public health risk. Here, we use humanized mice to show that CWD prions can cross the species barrier to humans, and remarkably, infectious prions can be excreted in feces.

Our results indicate that if CWD crosses the species-barrier to humans, it is unlikely to resemble the most common forms of human prion diseases with respect to clinical signs, tissue tropism and PrPSc signature. For instance, PrPSc in variable protease-sensitive prionopathy (VPSPr), a sporadic form of human prion disease, and in the genetic form Gerstmann-Sträussler-Scheinker syndrome (GSS) is defined by an atypical PK-resistant PrPSc fragment that is non-glycosylated and truncated at both C- and N-termini, with a molecular weight between 6 and 8 kDa [24, 44–46]. These biochemical features are unique and distinctive from PrPSc (PrP27-30) found in most other human or animal prion disease. The atypical PrPSc signature detected in brain homogenate of tg650 mice #321 (1st passage) and #3063 (2nd passage), and the 7–8 kDa fragment (Figs. 2, 4) are very similar to that of GSS, both in terms of migration profile and the N-terminal cleavage site.

CWD in humans might remain subclinical but with PrPSc deposits in the brain with an unusual morphology that does not resemble the patterns usually seen in different prion diseases (e.g., mouse #328; Fig. 3), clinical with untraceable abnormal PrP (e.g., mouse #327) but still transmissible and uncovered upon subsequent passage (e.g., mouse #3063; Fig. 4), or prions have other reservoirs than the usual ones, hence the presence of infectivity in feces (e.g., mouse #327) suggesting a potential for human-to-human transmission and a real iatrogenic risk that might be unrecognizable.

suggesting a potential for human-to-human transmission and a real iatrogenic risk that might be unrecognizable.

=================================

Supplementary Information The online version contains supplementary material available at

https://doi.org/10.1007/s00401-022-02482-9

snip...see full text;

https://link.springer.com/article/10.1007/s00401-022-02482-9

https://link.springer.com/content/pdf/10.1007/s00401-022-02482-9.pdf

Friday, October 20, 2023

An investigation has been opened into the death of a scientist who was studying a transmissible and deadly disease CJD in Spain

https://itseprion.blogspot.com/2023/10/an-investigation-has-been-opened-into.html

THURSDAY, OCTOBER 19, 2023

CWD TSE PRION CERVID ENVIRONMENTAL RISK FACTORS 2023

https://chronic-wasting-disease.blogspot.com/2023/10/cwd-tse-prion-cervid-environmental-risk.html

Control of Chronic Wasting Disease OMB Control Number: 0579-0189APHIS-2021-0004 Singeltary Submission

https://www.regulations.gov/comment/APHIS-2021-0004-0002

https://downloads.regulations.gov/APHIS-2021-0004-0002/attachment_1.pdf

Docket No. APHIS-2018-0011 Chronic Wasting Disease Herd Certification

https://www.regulations.gov/document/APHIS-2018-0011-0003

https://downloads.regulations.gov/APHIS-2018-0011-0003/attachment_1.pdf

APHIS Indemnity Regulations [Docket No. APHIS-2021-0010] RIN 0579-AE65 Singeltary Comment Submission

Comment from Singeltary Sr., Terry

Posted by the Animal and Plant Health Inspection Service on Sep 8, 2022

https://www.regulations.gov/comment/APHIS-2021-0010-0003

https://downloads.regulations.gov/APHIS-2021-0010-0003/attachment_1.pdf

Docket No. FDA-2003-D-0432 (formerly 03D-0186) Use of Material from Deer and Elk in Animal Feed

PUBLIC SUBMISSION

Comment from Terry Singeltary Sr.

Posted by the Food and Drug Administration on May 17, 2016 Comment

Docket No. FDA-2003-D-0432 (formerly 03D-0186) Use of Material from Deer and Elk in Animal Feed Singeltary Submission

https://www.regulations.gov/comment/FDA-2003-D-0432-0011

https://www.regulations.gov/docket/FDA-2003-D-0432

Texas CWD Surveillance Positives as of today, this page is woefully outdated!

https://tpwd.texas.gov/huntwild/wild/diseases/cwd/positive-cases/listing-cwd-cases-texas.phtml#texasCWD

Counties where CWD Exposed Deer were Released

https://tpwd.texas.gov/documents/257/CWD-Trace-OutReleaseSites.pdf

Number of CWD Exposed Deer Released by County

https://tpwd.texas.gov/documents/258/CWD-Trace-OutReleaseSites-NbrDeer.pdf

Chronic Wasting Disease CWD Captive Herds updated April 2023

https://www.aphis.usda.gov/aphis/ourfocus/animalhealth/animal-disease-information/cervid/cervids-cwd/cervids-voluntary-hcp

Chronic Wasting Disease CWD Captive Herds updated April 2023

https://www.aphis.usda.gov/animal_health/animal_diseases/cwd/downloads/status-of-captive-herds.pdf

TPWD Executive Order No. 23-003 CWD Emergency Rules Adopted for Movement of Breeder Deer

Executive Orders

2023

Executive Order No. 23-003

Date: July 24, 2023

The Executive Director finds that additional discoveries of CWD in free-ranging white-tailed deer within deer breeding facilities regulated under Parks and Wildlife Code, Chapter 43, Subchapter L and regulations adopted pursuant to that subchapter (31 TAC Chapter 65, Subchapters B and T) constitute an immediate danger to the white-tailed deer and mule deer resources of Texas and that the adoption of rules on an emergency basis with fewer than 30 days’ notice is necessary to address an immediate danger.

https://tpwd.texas.gov/publications/executive_orders/

15 minute mark video shows sick deer with cwd, and this deer DIED FROM CWD, IT'S DOCUMENTED, commentator says ''so if anyone every tells you, that a deer has never died from CWD, think of this picture, because the Wisconsin Veterinary Lab told us, what when they looked at her sample under a microscope, she was the hottest animal they had ever seen, and that's in terms of the fluorescents that comes off the slide when the look at it, so, a lot of Prion in her system.''

see much more about 2 hours long...

https://www.youtube.com/watch?v=O3CAI-EwlgM

TEXAS BREEDER DEER ESCAPEE WITH CWD IN THE WILD, or so the genetics would show?

OH NO, please tell me i heard this wrong, a potential Texas captive escapee with cwd in the wild, in an area with positive captive cwd herd?

apparently, no ID though. tell me it ain't so please...

23:00 minute mark

''Free Ranging Deer, Dr. Deyoung looked at Genetics of this free ranging deer and what he found was, that the genetics on this deer were more similar to captive deer, than the free ranging population, but he did not see a significant connection to any one captive facility that he analyzed, so we believe, Ahhhhhh, this animal had some captive ahhh, whatnot.''

https://youtu.be/aoPDeGL6mpQ?t=1384

Commission Agenda Item No. 5 Exhibit B

DISEASE DETECTION AND RESPONSE RULES

PROPOSAL PREAMBLE

1. Introduction.

snip...

A third issue is the accuracy of mortality reporting. Department records indicate that for each of the last five years an average of 26 deer breeders have reported a shared total of 159 escapes. Department records for the same time period indicate an average of 31 breeding facilities reported a shared total of 825 missing deer (deer that department records indicate should be present in the facility, but cannot be located or verified).

https://tpwd.texas.gov/business/feedback/meetings/2022/1104/agenda/item.phtml?item=5

On January 21, 2017 a tornado took down thousands of feet of fence for a 420-acre illegal deer enclosure in Lamar County that had been subject to federal and state investigation for illegally importing white-tailed deer into Mississippi from Texas (a CWD positive state). Native deer were free to move on and off the property before all of the deer were able to be tested for CWD. Testing will be made available for a period of three years for CWD on the property and will be available for deer killed within a 5-mile radius of the property on a voluntary basis.

https://www.mdwfp.com/media/254796/2016-17-deer-report.pdf

“It is interesting to note that, in 2001, the State of Texas shifted its deer management strategies toward the same leanings that Kroll has suggested for Wisconsin. In Texas, the change was brought about via heavy lobbying from the high-fence deer ranching industry. This pressure helped convince the Texas Parks and Wildlife to change their regulations and allow private landowners to select the own deer biologists.”

http://www.texasmonthly.com/story/which-side-fence-are-you

2012 “For 10 years, Texas has had an aggressive Chronic Wasting Disease prevention and monitoring program. Wildlife agency regulations prohibit importing deer into the state, and the agency has tested more than 26,000 hunter-taken deer and 7,400 animals from the captive-deer industry. None of those deer tested positive.”

http://www.chron.com/news/houston-texas/article/Brain-eating-disease-found-in-Texas-deer-3697731.php

Terry S. Singeltary Sr., Bacliff, Texas USA 77518 flounder9@verizon.net

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

Chronic Wasting Disease

Friday, October 20, 2023

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

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