Thursday, January 4, 2024

Disease phenotype of classical sheep scrapie is changed upon experimental passage through white-tailed deer

 PLoS Pathog. 2023 Dec; 19(12): e1011815. Published online 2023 Dec 4. https://doi.org/10.1371/journal.ppat.1011815 


PMCID: PMC10721168 PMID: 38048370 

Disease phenotype of classical sheep scrapie is changed upon experimental passage through white-tailed deer 

Robyn D. Kokemuller, Formal analysis, Investigation, Writing – original draft, Writing – review & editing, 1 S. Jo Moore, Formal analysis, Investigation, Writing – original draft, Writing – review & editing, 1 Jifeng Bian, Formal analysis, Investigation, Methodology, Writing – review & editing, 1 M. Heather West Greenlee, Conceptualization, Investigation, Supervision, Writing – review & editing, 2 and Justin J. Greenlee, Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Project administration, Resources, Supervision, Writing – original draft, Writing – review & editing corresponding author 1 ,* Jason C. Bartz, Editor Author information Article notes Copyright and License information Associated Data Supplementary Materials Data Availability Statement 

Abstract 

Prion agents occur in strains that are encoded by the structure of the misfolded prion protein (PrPSc). Prion strains can influence disease phenotype and the potential for interspecies transmission. Little is known about the potential transmission of prions between sheep and deer. Previously, the classical US scrapie isolate (No.13-7) had a 100% attack rate in white-tailed deer after oronasal challenge. The purpose of this study was to test the susceptibility of sheep to challenge with the scrapie agent after passage through white-tailed deer (WTD scrapie). Lambs of various prion protein genotypes were oronasally challenged with WTD scrapie. Sheep were euthanized and necropsied upon development of clinical signs or at the end of the experiment (72 months post-inoculation). Enzyme immunoassay, western blot, and immunohistochemistry demonstrated PrPSc in 4 of 10 sheep with the fastest incubation occurring in VRQ/VRQ sheep, which contrasts the original No.13-7 inoculum with a faster incubation in ARQ/ARQ sheep. Shorter incubation periods in VRQ/VRQ sheep than ARQ/ARQ sheep after passage through deer was suggestive of a phenotype change, so comparisons were made in ovinized mice and with sheep with known strains of classical sheep scrapie: No. 13–7 and x-124 (that has a more rapid incubation in VRQ/VRQ sheep). After mouse bioassay, the WTD scrapie and x-124 isolates have similar incubation periods and PrPSc conformational stability that are markedly different than the original No. 13–7 inoculum. Furthermore, brain tissues of sheep with WTD scrapie and x-124 scrapie have similar patterns of immunoreactivity that are distinct from sheep with No. 13–7 scrapie. Multiple lines of evidence suggest a phenotype switch when No. 13–7 scrapie prions are passaged through deer. This represents one example of interspecies transmission of prions resulting in the emergence or selection of new strain properties that could confound disease eradication and control efforts.

Author summary Passage of the sheep-derived US No. 13–7 classical scrapie isolate through white-tailed deer results in a change in disease phenotype that is observed when the deer-passaged scrapie agent is inoculated back into sheep or ovinized mice. Upon passage back to sheep, the relationship between incubation period and sheep PRNP genotype is reversed from the original inoculum. Whereas inoculation with the original No.13-7 scrapie agent results in a shorter incubation period in sheep with the ARQ/ARQ genotype as compared to VRQ/VRQ sheep, the deer-passaged scrapie agent results in a shorter incubation period in VRQ/VRQ sheep. In addition, passage of the No.13-7 isolate through deer results in a change in the pattern of PrPSc deposition in the brain of affected sheep. Taken together with the results of bioassay and conformational stability assays this work supports emergence of strain properties different from the No. 13–7 inoculum and consistent with another classical scrapie strain called x-124. Interspecies transmission of the classical scrapie agent can result in a phenotype switch through emergence of new scrapie strain properties that could potentially expand the potential host range.

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In summary, this work demonstrates that interspecies transmission of prion isolates can result in the emergence of new strain properties that could alter the host range or require different management strategies to control disease spread.

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Detection of classical BSE prions in asymptomatic cows after inoculation with atypical/Nor98 scrapie

Marina Betancor1, Belén Marín1, Alicia Otero1#, Carlos Hedman1, Antonio Romero2, Tomás Barrio3, Eloisa Sevilla1, Jean Yves Douet3, Alvina Huor3, Juan José Badiola1, Olivier Andréoletti3, Rosa Bolea1.

1Centro de Encefalopatías y Enfermedades Transmisibles Emergentes, Facultad de Veterinaria, Universidad de Zaragoza, Instituto Agroalimentario de Aragón - IA2, 50013, Zaragoza, Spain. 2 Servicio de Cirugía y Medicina Equina, Hospital Veterinario, Universidad de Zaragoza, 50013, Zaragoza, Spain 3 UMR École Nationale Vétérinaire de Toulouse (ENVT) - Institut National pour l’Agriculture, l’Alimentation et l’Environnement (INRAE) - 1225 Interactions Hôtes Agents Pathogènes (IHAP), 31300 Toulouse, France.

Aims: The emergence of bovine spongiform encephalopathy (BSE) prions from atypical scrapie has been recently proved in rodent and swine models. This study aimed to assess whether the inoculation of atypical scrapie could induce BSE-like disease in cattle.

Materials and Methods: Four calves were intracerebrally challenged with atypical scrapie. Animals were euthanized without clinical signs of prion disease between 7.2 and 11.3 years post-inoculation and tested for the accumulation of prions by conventional techniques and protein misfolding cyclic amplification (PMCA).

Results: None of the bovines showed signs compatible with prion disease. In addition, all tested negative for PrPSc accumulation by immunohistochemistry and western blotting. However, an emergence of BSE-like prions was detected during in vitro propagation of brain samples from the inoculated animals.

Conclusions: These findings suggest that atypical scrapie may represent a potential source of BSE infection in cattle.

Funded by: This work was supported financially by the following Spanish and European Interreg grants: Ministerio de Ciencia, Innovación y Universidades (Spanish Government), cofunded by Agencia Estatal de Investigación and the European Union and POCTEFA, which was 65% co-financed by the European Regional Development Fund (ERDF) through the Interreg V-A Spain-France-Andorra program (POCTEFA 2014– 2020).

Grant number: n° PID2021-125398OB-I00, EFA148/16 REDPRION

Acknowledgement: The authors would like to thank Sandra Felices and Daniel Romanos for their excellent technical assistance. Authors would also like to acknowledge the use of Servicio General de Apoyo a la Investigación-SAI, Universidad de Zaragoza

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Evolution of Nor98/ Atypical scrapie by iterative propagation in a homologous ovine PrPC context

Sara Canoyra1, Alba Marín-Moreno1, Juan Carlos Espinosa1, Natalia Fernández-Borges1, Nuria Jerez-Garrido1, Sylvie L. Benestad2, Enric Vidal3, Leonor Orge4, Olivier Andreoletti5 and Juan María Torres1.

1Centro de Investigación en Sanidad Animal, CISA-INIA-CSIC, Madrid, Spain. 2Norwegian Veterinary Institute, Ås, Norway. 3Centre de Recerca en Sanitat Animal, Universitat Autònoma de Barcelona (UAB)–Institut de Recerca i Tecnologia Agroalimentàries, Barcelona, Spain. 4Laboratory of Pathology, National Institute for Agrarian and Veterinary Research, Oeiras, Portugal 5UMR Institut National de la Recherche Agronomique (INRA)/École Nationale Vétérinaire de Toulouse (ENVT), Interactions Hôtes Agents Pathogènes, Toulouse, France

Aims: Nor98/ Atypical scrapie (AS) is a prion disease that causes sporadic casesin sheep and goats. Previous studies have shown that the transmission of AS to otherspecies led to the emergence of new prion strains. In the bovine and porcine PrP, there has been reported the emergence of classical BSE prions (Huor et al., 2019, Espinosa et al., 2009, Marin et. al., 2021) and in the bank vole M109I-PrP context, a classical scrapie-like prion strain emerges(Pirisinu et al., 2022). In this study, we analysed the possible evolution of the AS prion within the same specie by modelling the transmission in a homologous ovine PrP context.

Materials and Methods: A panel of AS isolates with different genotypes and geographical origins both from sheep and goats were inoculated in the wild-type transgenic mice model (ARQ-PrP, Aguilar-Calvo et al., 2014).

Results: The isolates infect the ovine ARQ-PrP mice with homogeneous survival time and a complete attack rate. For several AS isolatesthe transmission led to the emergence of 19kDa (with BSE-like characteristics), 21kDa or atypical prions and mixtures of these agents.

Conclusions:

Iterative subpassages of AS isolates into transgenic mice carrying ovine PrP showed an emergence of classical prions during in vivo propagation. This could be caused by the coexistence of strains in the isolate or the evolution of the AS through propagation in the ovine PrP.

These results allow us to hypothesize whether atypical prions might be the origin of prion diversity, where atypical prions tend to acquire classical forms. These results are relevant to control the exposure of farmed animals and humans to AS.

Funded by: MCIN/AEI/ 10.13039/501100011033 Grant number: PID2019-105837RB-I00

Conformational shift as the evolutionary mechanism for classical BSE emergence from atypical scrapie

Sara Canoyra, Alba Marín-Moreno, Juan Carlos Espinosa, Natalia Fernández- Borges, and Juan María Torres

Centro de Investigación en Sanidad Animal, CISA-INIA-CSIC, Valdeolmos, Madrid, Spain

Aims: New prion strains emerge when the prion conformational characteristics change during intra- or cross-species transmission. There are two main theories, non-mutually exclusive, that could explain this phenomenon: the ‘deformed templating’ and the ‘conformational selection model’. According to the ‘deformed templating’ or mutation model, when the prion is unable to replicate in a new host there is a shift to a new PrPSc conformation. On the other hand, the ‘conformational selection’ theory postulates that prion isolates are a conglomerate of conformations and during cross-species transmission the species barrier acts as a filter.

In previous studies, we showed the emergence of the bovine spongiform encephalopathy agent (C-BSE) due to the transmission of atypical scrapie (AS) onto bovine PrP. This work will elucidate the evolutionary dichotomy in the AS transmission, providing supporting evidence on the hypothesis of the origin of the epidemic C-BSE prion from AS.

Material and Methods: A panel of AS isolates with different genotypes and geographical distribution was analyzed. To differentiate between AS and C-BSE two strain typing features were used: thermostability and PMCA propagation. The AS isolates underwent a heat treatment of 98°C during 2 h and were amplified in vitro by PMCA in bovine PrPC substrate. The templating activity with or without heat was determine after 10 amplification rounds by western blot characterization.

In addition, we analyzed an artificial mixture of AS and C-BSE generated by diluting C- BSE in a constant amount of AS.

Results: We observed a drastic loss in the C-BSE emergence due to the heat treatment. The AS is a thermolabile prion. Hence, the inactivation of the AS conformers with the ability to shift the conformation will slow down the emergence of the C-BSE.

In contrast, when we analyzed the artificial mixture C-BSE prions emerge even with the heat treatment. Therefore, if the AS isolates had contained a minoritarian C-BSE conformer (defended by the conformational selection model) the emergence wouldn’t have been affected by the heat.

Conclusions: Mutation is the main evolutionary mechanism responsible for the C-BSE emergence. The species barrier forces the shift to a possible structure (C-BSE in this case) in a thermodynamically unfavorable process.

This discovery reenforces the origin hypothesis of the epidemic C-BSE as a contact of the cattle with feed contaminated with AS. Where the AS will evolve shifting to a C-BSE stable conformation. This also has implications in the control of farmed animals and humans’ exposure to the AS.

Funded by:/Grant number: Project PID2019-105837RB-I00 MCIN/ AEI /10.13039/501,100,011,033 Fundación La Marató de TV3 Enfermedades

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https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9467582/



The emergence of classical BSE from atypical/Nor98 scrapie

Alvina Huor, Juan Carlos Espinosa https://orcid.org/0000-0002-6719-9902, Enric Vidal https://orcid.org/0000-0002-4965-3286, +15, and Olivier Andreoletti 

https://orcid.org/0000-0002-7369-6016 o.andreoletti@envt.fr Authors Info & Affiliations

Edited by Michael B. A. Oldstone, Scripps Research Institute, La Jolla, CA, and approved November 15, 2019 (received for review September 11, 2019) December 16, 2019

116 (52) 26853-26862


Significance

The origin of transmissible BSE in cattle remains unestablished. Sheep scrapie is a potential source of this known zoonotic. Here we investigated the capacity of sheep scrapie to propagate in bovine PrP transgenic mice. Unexpectedly, transmission of atypical but not classical scrapie in bovine PrP mice resulted in propagation of classical BSE prions. Detection of prion seeding activity by in vitro protein misfolding cyclic amplification demonstrated BSE prions in the original atypical scrapie isolates. BSE prion seeding activity was also detected in ovine PrP mice inoculated with limiting dilutions of atypical scrapie. Our data demonstrate that classical BSE prions can emerge during intra- and interspecies passage of atypical scrapie and provide an unprecedented insight into the evolution of mammalian prions.

Abstract

Atypical/Nor98 scrapie (AS) is a prion disease of small ruminants. Currently there are no efficient measures to control this form of prion disease, and, importantly, the zoonotic potential and the risk that AS might represent for other farmed animal species remains largely unknown. In this study, we investigated the capacity of AS to propagate in bovine PrP transgenic mice. Unexpectedly, the transmission of AS isolates originating from 5 different European countries to bovine PrP mice resulted in the propagation of the classical BSE (c-BSE) agent. Detection of prion seeding activity in vitro by protein misfolding cyclic amplification (PMCA) demonstrated that low levels of the c-BSE agent were present in the original AS isolates. C-BSE prion seeding activity was also detected in brain tissue of ovine PrP mice inoculated with limiting dilutions (endpoint titration) of ovine AS isolates. These results are consistent with the emergence and replication of c-BSE prions during the in vivo propagation of AS isolates in the natural host. These data also indicate that c-BSE prions, a known zonotic agent in humans, can emerge as a dominant prion strain during passage of AS between different species. These findings provide an unprecedented insight into the evolution of mammalian prion strain properties triggered by intra- and interspecies passage. From a public health perspective, the presence of c-BSE in AS isolates suggest that cattle exposure to small ruminant tissues and products could lead to new occurrences of c-BSE.

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Classical BSE was first recognized in 1984 and 1985 as a novel prion disease affecting cattle in the United Kingdom (40). Epidemiological data clearly established that the number of cases of c-BSE was amplified by the recycling of infected animal carcasses into cattle feed in the form of meat and bone meal (MBM) (41). Since bovine prion disease had not been recognized in cattle prior to the c-BSE epizootic and the disease is apparently noncontagious between cattle, several hypotheses were proposed to explain its emergence. These range from the spontaneous occurrence of c-BSE in cattle to the passage and adaptation of a prion originating from another species (42, 43). Our studies here that show the presence of c-BSE prions in AS isolates, combined with the demonstrated presence of AS in the United Kingdom long before the appearance of the c-BSE epizootic in cattle, suggests that the recycling of AS cases in MBM might be a source of bovine prion disease (20). In addition to its potential role in the initial emergence of c-BSE in cattle, the presence of c-BSE prions in natural cases of AS has current and direct implications for both the continued risk of this ovine prion disease to other farmed animals and for human exposure risks. The distribution of AS cases are widespread across the world (17–19). A recent retrospective analysis of surveillance data collected over a period exceeding 10 y in the European Union (EU) concluded that the prevalence of detected AS cases has remained relatively stable in the different member states, with between 2 and 6 positive cases per 10,000 tested animals per year. This implies that a substantial number of AS-infected animals could enter either the animal or human food chain each year (44, 45), and each case represents a potential source of exposure to the c-BSE agent for farmed animals (MBM derived from rendered small ruminants) and human consumers (consumption of healthy slaughtered animals), respectively. The epidemiological features of AS within the EU is likely to reflect the situation of the disease in other countries that breed and maintain small ruminants. 

In Europe, the c-BSE crisis and the emergence of vCJD resulted in the implementation of a strong and coherent policy (EU regulation 999/2001) aimed at control and eradication of this animal prion disease. The total feed ban on the use of MBM in animal feed and the systematic retrieval from the food chain of ruminant tissues that have the potential to contain high levels of prion infectivity, so-called Specified Risk Material (SRM) measures, were instrumental for control of c-BSE in cattle and prevention of dietary human exposure to these bovine prions (46, 47). As a side effect, these measures also strongly limited the exposure of farmed animals and human consumers to the other TSE agents circulating in farmed animal species, including AS. 

With the decline of the c-BSE epizootic in cattle and the combined increase in pressure from industry, EU authorities have begun to consider discontinuing certain TSE control measures. The abrogation of the SRM measures for small ruminants and the partial reauthorization of the use of processed animal protein, formerly known as MBM, in animal feed are part of the EU authorities’ agenda. Our observation of the presence of the c-BSE agent in AS-infected small ruminants suggests that modification of the TSE control measures could result in an increased risk of exposure to c-BSE prions for both animals and humans. Whether or not this exposure will result in further c-BSE transmission in cattle and/or humans remains an open and important question.


Monday, November 13, 2023

Food and Drug Administration's BSE Feed Regulation (21 CFR 589.2000) Singeltary Another Request for Update 2023


BSE prions propagate as either variant CJD-like or sporadic CJD-like prion strains in transgenic mice expressing human prion protein

Emmanuel A.Asante, Jacqueline M.Linehan, Melanie Desbruslais, Susan Joiner, Ian Gowland, Andrew L.Wood, Julie Welch, Andrew F.Hill, Sarah E.Lloyd, Jonathan D.F.Wadsworth and John Collinge1

MRC Prion Unit and Department of Neurodegenerative Disease, Institute of Neurology, University College, Queen Square, London WC1N 3BG, UK 1 Corresponding author e-mail: j.collinge@prion.ucl.ac.uk

Variant Creutzfeldt±Jakob disease (vCJD) has been recognized to date only in individuals homozygous for methionine at PRNP codon 129. Here we show that transgenic mice expressing human PrP methionine 129, inoculated with either bovine spongiform encephalopathy (BSE) or variant CJD prions, may develop the neuropathological and molecular phenotype of vCJD, consistent with these diseases being caused by the same prion strain. Surprisingly, however, BSE transmission to these transgenic mice, in addition to producing a vCJD-like phenotype, can also result in a distinct molecular phenotype that is indistinguishable from that of sporadic CJD with PrPSc type 2. These data suggest that more than one BSEderived prion strain might infect humans; it is therefore possible that some patients with a phenotype consistent with sporadic CJD may have a disease arising from BSE exposure.

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These studies further strengthen the evidence that vCJD is caused by a BSE-like prion strain. Also, remarkably, the key neuropathological hallmark of vCJD, the presence of abundant ¯orid PrP plaques, can be recapitulated on BSE or vCJD transmission to these mice. However, the most surprising aspect of the studies was the ®nding that an alternate pattern of disease can be induced in 129MM Tg35 mice from primary transmission of BSE, with a molecular phenotype indistinguishable from that of a subtype of sporadic CJD. This ®nding has important potential implications as it raises the possibility that some humans infected with BSE prions may develop a clinical disease indistinguishable from classical CJD associated with type 2 PrPSc. This is, in our experience, the commonest molecular sub-type of sporadic CJD. In this regard, it is of interest that the reported incidence of sporadic CJD has risen in the UK since the 1970s (Cousens et al., 1997). This has been attributed to improved case ascertainment, particularly as much of the rise is reported from elderly patients and similar rises in incidence were noted in other European countries without reported BSE (Will et al., 1998). However, it is now clear that BSE is present in many European countries, albeit at a much lower incidence than was seen in the UK. While improved ascertainment is likely to be a major factor in this rise, that some of these additional cases may be related to BSE exposure cannot be ruled out. It is of interest in this regard that a 2-fold increase in the reported incidence of sporadic CJD in 2001 has recently been reported for Switzerland, a country that had the highest incidence of cattle BSE in continental Europe between 1990 and 2002 (Glatzel et al., 2002). No epidemiological case±control studies with strati®cation of CJD cases by molecular sub-type have yet been reported. It will be important to review the incidence of sporadic CJD associated with PrPSc type 2 and other molecular subtypes in both BSE-affected and unaffected countries in the light of these ®ndings. If human BSE prion infection can result in propagation of type 2 PrPSc, it would be expected that such cases would be indistinguishable on clinical, pathological and molecular criteria from classical CJD. It may also be expected that such prions would behave biologically like those isolated from humans with sporadic CJD with type 2 PrPSc. The transmission properties of prions associated with type 2 PrPSc from BSE-inoculated 129MM Tg35 mice are being investigated by serial passage.

We consider these data inconsistent with contamination of some of the 129MM Tg35 mice with sporadic CJD prions. These transmission studies were performed according to rigorous biosafety protocols for preparation of inocula and both the inoculation and care of mice, which are all uniquely identi®ed by sub-cutaneous transponders. However, crucially, the same BSE inocula have been used on 129VV Tg152 and 129MM Tg45 mice, which are highly sensitive to sporadic CJD but in which such transmissions producing type 2 PrPSc were not observed. Furthermore, in an independent experiment, separate inbred lines of wild-type mice, which are highly resistant to sporadic CJD prions, also propagated two distinctive PrPSc types on challenge with either BSE or vCJD. No evidence of spontaneous prion disease or PrPSc has been seen in groups of uninoculated or mock-inoculated aged 129MM Tg35 mice.

While distinctive prion isolates have been derived from BSE passage in mice previously (designated 301C and 301V), these, in contrast to the data presented here, are propagated in mice expressing different prion proteins (Bruce et al., 1994). It is unclear whether our ®ndings indicate the existence of more than one prion strain in individual cattle with BSE, with selection and preferential replication of distinct strains by different hosts, or that `mutation' of a unitary BSE strain occurs in some types of host. Western blot analysis of single BSE isolates has not shown evidence of the presence of a proportion of monoglycosylated dominant PrPSc type in addition to the diglycosylated dominant pattern (data not shown). Extensive strain typing of large numbers of individual BSE-infected cattle either by biological or molecular methods has not been reported.

Presumably, the different genetic background of the different inbred mouse lines is crucial in determining which prion strain propagates on BSE inoculation. The transgenic mice described here have a mixed genetic background with contributions from FVB/N, C57BL/6 and 129Sv inbred lines; each mouse will therefore have a different genetic background. This may explain the differing response of individual 129MM Tg35 mice, and the difference between 129MM Tg35 and 129MM Tg45 mice, which are, like all transgenic lines, populations derived from single founders. Indeed, the consistent distinctive strain propagation in FVB and C57BL/6 versus SJL and RIIIS lines may allow mapping of genes relevant to strain selection and propagation, and these studies are in progress.

That different prion strains can be consistently isolated in different inbred mouse lines challenged with BSE prions argues that other species exposed to BSE may develop prion diseases that are not recognizable as being caused by the BSE strain by either biological or molecular strain typing methods. As with 129MM Tg35 mice, the prions replicating in such transmissions may be indistinguishable from naturally occurring prion strains. It remains of considerable concern whether BSE has transmitted to, and is being maintained in, European sheep flocks. Given the diversity of sheep breeds affected by scrapie, it has to be considered that some sheep might have become infected with BSE, but propagated a distinctive strain type indistinguishable from those of natural sheep scrapie.


WEDNESDAY, JANUARY 3, 2024 

PROCEEDINGS ONE HUNDRED AND TWENTY SIXTH ANNUAL MEETING USAHA CWD, Scrapie, and BSE, October 2022 updated science 2024


PLEASE NOTE, CJD IS NOW 1 IN 5,000 GLOBALLY, COLLINGE ET AL 2023!

Professor John Collinge on tackling prion diseases, sCJD accounts for around 1 in 5000 deaths worldwide

MONDAY, SEPTEMBER 11, 2023 

Professor John Collinge on tackling prion diseases “The best-known human prion disease is sporadic Creutzfeldt-Jakob disease (sCJD), a rapidly progressive dementia which accounts for around 1 in 5000 deaths worldwide.” There is accumulating evidence also for iatrogenic AD. Understanding prion biology, and in particular how propagation of prions leads to neurodegeneration, is therefore of central research importance in medicine.



MONDAY, DECEMBER 18, 2023

Change in Epidemiology of Creutzfeldt-Jakob Disease in the US, 2007-2020


TUESDAY, DECEMBER 12, 2023 

CREUTZFELDT JAKOB DISEASE TSE PRION DISEASE UPDATE USA DECEMBER 2023 



Terry S. Singeltary Sr.

Wednesday, January 3, 2024

PROCEEDINGS ONE HUNDRED AND TWENTY SIXTH ANNUAL MEETING USAHA CWD, Scrapie, and BSE, October 2022 updated science 2024

PROCEEDINGS ONE HUNDRED AND TWENTY SIXTH ANNUAL MEETING USAHA CWD, Scrapie, and BSE, October 2022 updated science 2024


PROCEEDINGS ONE HUNDRED AND TWENTY SIXTH ANNUAL MEETING USAHA CWD, Scrapie, and BSE, October 6-12, 2022

PROCEEDINGS ONE HUNDRED AND TWENTY SIXTH ANNUAL MEETING of the United States Animal Health Association 

Hyatt Regency Hotel HYBRID Minneapolis, Minnesota October 6-12, 2022

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Presentations and Reports

2022 USAHA Cervid Section Summary USDA-APHIS-VS Cervid Health Program Tracy Nichols, USDA-Animal and Plant Health Inspection Service (APHIS) FY2022 CWD Detections in Farmed Cervids: There were 23 new chronic wasting disease (CWD) positive farmed cervid herds in FY22 (18 white-tailed deer, 3 elk, 2 mixed species herds). Fifteen of the herds were not participants in the Federal Herd Certification Program (HCP), two were enrolled, but not certified in the HCP, and six were certified in the HCP. Nineteen of the 23 newly identified herds were in areas where CWD has been found within 20 miles in wild cervid populations.

CWD Research: APHIS, Veterinary Services (VS) continues to partner with a variety of CWD researchers such as Dr. Chris Seabury from Texas A&M to investigate and expand CWD predictive genetics in white-tailed deer. The data from this study continues to provide useful information. In FY22, three states were funded with CWD Cooperative agreements to utilize a predictive genetics approach to assist producers in establishing their breeding values. VS has also funded Dr. Seabury, via a cooperative agreement with the Texas Animal Health Commission, to develop a predictive genetics approach in elk. Collaboration with USDA Agricultural Research Service (ARS) Pullman and Ames, United States Geological Survey (USGS), University of Wisconsin, Madison, and University of Minnesota, has determined the sensitivity and specificity of real-time quaking-induced conversion (RT-QuIC) in tonsil biopsy and postmortem medial retropharyngeal lymph nodes. A cross laboratory reproducibility study has been conducted and a data package is being prepared to be submitted to the USDA National Veterinary Services Laboratories (NVSL) for review. A blinded postmortem RT-QuIC sensitivity and specificity study has been completed on medial retropharyngeal lymph nodes and the bioassay portion will be starting soon.

Tuberculosis (TB) and Brucellosis: The brucellosis and TB rules are still under development at this time. A total of 9,178 TB tests were conducted in FY21 (7,595 DPP and 1,583 SCT).

Discussion of Proximity Barriers/ Restrictions in Determining Importation of Herd Certification Programs (HCP) Herds

Scott Leibsle, Idaho State Department of Agriculture

The variability of import requirements for domestic cervids relative to chronic wasting disease (CWD) spans a wide regulatory spectrum. The genesis of these regulations is typically unique to each state and are a product of rules negotiation of policy and politics, absent of scientific evidence. The wide variability of these regulations is both difficult for state animal health officials to enforce and an onerous burden upon the industries that are subject to them. The CWD import regulatory spectrum spans from HCP compliance (minimum), endemic area restrictions, proximities to CWD positive wild cervids, restriction from affected states or provinces or a total import moratorium (maximum). Efforts to harmonize import requirements for CWD as well as other entry criteria that are based upon appropriate scientific evidence should be maximized to ease both regulatory burdens and impacts upon commerce and trade.

Chronic Wasting Disease (CWD) Program Standards – Time for a New Look and Need for a Rewrite

Paul Anderson, Minnesota Board of Animal Health

Dr. Anderson spoke about the need to change how we control CWD in the United States and the need to rewrite the CWD Program Standards. He provided content for how our understanding of the disease and its distribution has changed. He discussed, from a producer perspective, why the CWD Program Standards should be rewritten. Dr. Anderson

123 FARMED CERVIDAE

presented a draft rewrite of the CWD Program Standards that supports the requirements specified in 9 CFR 55 and 81 and outlines a program to control CWD in farmed cervid herds without causing unnecessary harm to cervid producers.

Committee Business:

Travis Lowe, from the North American Elk Breeders Association, read his resolution requesting USAHA to urge state animal health officials and/or state wildlife officials that govern state import requirements of farmed cervidae to use proximity restrictions based off known peer reviewed science that specifically caters to applicable species. Mark Luedtke made a motion to approve the resolution and Gary Olson seconded the motion. Discussion on the resolution ensued.

A motion was made by Hunter Reed, seconded by Paul Anderson, to amend the resolution to change the last sentence to say, “based off known best available science that can be made publicly available”.

After discussion, Charly Seale called for a show of hands for and then against the amendment. The motion to amend the resolution passed. Back to the motion to approve, Charly Seale called for a vote on the resolution and by a show of hands the resolution was approved.

Proposed Recommendation

Charly Seale reviewed the recommendation, drafted by Dr. Paul Anderson, stating the USAHA Committee on Farmed Cervidae recommends to the United States Department of Agriculture (USDA), Animal and Plant Health Inspection Service (APHIS), Veterinary Services (VS) that the document entitled, Chronic Wasting Disease Program Standards be completely rewritten and replaced with the document entitled, Chronic Wasting Disease (CWD) Industry/State/Federal Program Standards (visit https://www.usaha.org/farmedcervidae). A motion was made by Mark Luedtke to approve the recommendation. The motion was seconded by Jacques DeMoss.

A motion was made by Scott Leibsle, seconded by Paul Anderson, to amend the recommendation so that the revised CWD Program Standards serve as a template or reference/starting point for USDA to re-write the Program Standards. There was discussion that suggested the program needs to be modified to reflect current understandings of Chronic Wasting Disease but too many people were left out of the revision process. The overwhelmingly highly pathogenic avian influenza (HPAI) response was discussed as a reason why USDA did not have time to work on the 2021 Resolution #3, requesting a revision of the Chronic Wasting Disease Program Standards. Charly Seale called for a show of hands to vote on the amendment. The motion to amend failed. Next, Charly Seale called for a vote on approving the recommendation to replace the current CWD Program Standards with the industry revision. The vote to approve the recommendation failed.

The meeting was adjourned at 3:10 p.m.

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RESOLUTION NUMBER: 30 APPROVED SOURCE: COMMITTEE ON WILDLIFE 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.

*******

RESOLUTION NUMBER: 31 APPROVED SOURCE: COMMITTEE ON FARMED CERVIDAE SUBJECT MATTER: PROXIMITY BARRIERS FOR INTERSTATE MOVEMENT OF FARMED CERVIDAE BACKGROUND INFORMATION:

The goal of the United States Department of Agriculture (USDA), Animal and Plant Health Inspection Service (APHIS) National CWD Voluntary Herd Certification Program, located in (9 Code of Federal Regulations Parts 55 & 81) is to provide a consistent national approach to control the incidence of chronic wasting disease (CWD) in farmed cervids and prevent the interstate spread of CWD. Farmed cervid herds must participate in the program and be certified to move animals interstate.

Some state regulatory officials governing interstate movement are utilizing their own authority to prohibit entry if the herd originates from an area within a specific proximity to a known CWD discovery in the free-ranging herd. Such guidance on proximity exclusions is

163 NOMINATIONS AND RESOLUTIONS

not included in the CWD Federal Rule or the APHIS Program Standards. State restrictions are inconsistent with examples showing mileage restrictions of 10 miles, 25 miles or 50 miles from a known CWD diagnosis or a herd’s location in relation to the home county, adjacent county or state.

The farmed cervid industry agreed to a federal layer of regulation aimed for consistency but the recent state action wanes the usefulness of the federal rule. Farmed cervid herds with more than twenty years of monitoring status and hundreds of post-mortem CWD nondetected samples are being restricted based on local environment status.

Such interstate movement restrictions are not based on peer-reviewed science that demonstrates specific range impacts of free-ranging discovery of the same cervid in relation to a farmed herd, specific range impacts of free-ranging discovery of a different cervid species in relation to a farmed herd, time elapsed since the free-ranging discovery and impacts to herds residing in double fenced facilities.

RESOLUTION: The United States Animal Health Association urges state animal health officials and/or state wildlife officials that govern state import requirements of farmed cervidae to use proximity restrictions based off best available science and the science be made publicly available.

snip...

Research Update from the National Animal Disease Center (NADC) Agricultural Research Service (ARS) Justin Greenlee, USDA-ARS

The Virus and Prion Research Unit at the National Animal Disease Center has ongoing research projects with the agents of scrapie, bovine spongiform encephalopathy, and chronic wasting disease (CWD). A project plan outlining the experiments for our four permanent scientists for the next five years was recently approved. The scrapie experiments in the plan are in two main categories: investigating atypical scrapie and the potential for the classical scrapie agent from goats to transmit to other species. The origin of bovine spongiform encephalopathy (BSE) in cattle is unknown, but it has been speculated that BSE came from the transmission of classical scrapie to cattle. Previous experiments conducted at the NADC and complimented by studies in the United Kingdom (UK) demonstrate that the lesions and molecular profile of PrPSc that result when the classical scrapie agent transmits to cattle are very different that BSE. However, recent studies demonstrate that when atypical scrapie prions are transmitted to mice expressing bovine prion protein the resulting PrPSc is indistinguishable from BSE. Therefore, we have initiated a study to investigate whether atypical scrapie prions will transmit to cattle and result in a BSE-like phenotype.

To investigate the transmission of classical scrapie prions from goats to other species we initiated studies in white-tailed deer and sheep. Whereas classical scrapie prions for sheep readily transmit to deer in an experimental setting, our recent work suggests that deer are not susceptible to classical scrapie prions from goats. Studies investigating the transmission of classical scrapie from goats to sheep are still underway, but early results suggest that transmission may be genotype dependent. Goat scrapie prions transmitted to 100% of ARQ/ARQ sheep exposed by the oronasal route. There was no evidence of PrPSc in VRQ/ARQ sheep tested after 70 months of incubation. Other genotypes of sheep are currently being studied.

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SUBCOMMITTEE ON SCRAPIE AND IDENTIFICATION

Chair: Larry Forgey, MO Vice Chair: Keith Forbes, NV Nancy Barr, MI; Nancy Brown, KS; Kathryn Carruth, TX; Keith Forbes, NV; Larry Forgey, MO; Kaylie Fritts, NE; Lance Gerlach, NC; Tracie Guy, FL; Daniel Hadacek, VA; Rod Hall, OK; Janemarie Hennebelle, GA; Julie Hurley, NH; Beth Johnson, KY; Jeffrey Kaisand, IA; Scott Leibsle, ID; Dave McElhaney, PA; Randy Munger, CO; Michael Neault, SC; Cheryl Nelson, KY; Elisabeth Patton, WI; Patty Scharko, SC; David Schneider, WA; Ryan Scholz, OR; Stacey Schwabenlander, MN; Tyler Thacker, IA; Marcus Webster, GA; Ryan Wolker, AZ; Cristopher Young, CO.

The Subcommittee met on October 9, 2022, in Minneapolis, Minnesota from 8:00-9:55 a.m. There were ten members, and two guests present virtually, and 29 members and guests present in-person. No previous resolutions needed to be reviewed and no new resolutions were brought to the committee at the meeting.

Presentations and Reports

American Sheep Industry (ASI) Perspective on the Future of the Cooperative Scrapie Eradication Program Amy Hendrickson, American Sheep Industry Ms. Hendrickson indicated that the scrapie program isn’t as front and center in most producer’s minds as we would like. Going forward, is the program going to focus on surveillance, traceability, or education? Discussion included the possibility of a seven-year rule which states without a scrapie case in the last seven years, could be rewarded with some form of scrapie-free state status.

National Scrapie Eradication Program Update

Diane Sutton, USDA-APHIS-VS

Over the last two decades, the National Scrapie Eradication Program (NSEP) has been very successful in reducing the prevalence of classical scrapie. Scrapie prevalence in the National Herd calculated using data from FY2017 through FY2021 has been reduced to <0.005% in sheep and <0.017% in goats. No positive animals have been identified since January 2021. In the last five fiscal years, there have been one positive sheep and two positive goats. The number of newly detected infected and source flocks peaked at 179 in FY2005. Forty-one states have not detected a case of classical scrapie in sheep in the last seven years and forty-seven states have not detected a case of scrapie in goats in seven years. These accomplishments have led the sheep and goat industries to ask the Animal Plant Health Inspection Service (APHIS), Veterinary Services (VS) to develop a definition of a scrapie free state. A draft definition has been developed and is being circulated for comment.

Despite the significant progress in eliminating scrapie, there is a high probability that classical cases still exist. In 2019, a goat was found to be positive at slaughter but could not be traced back to a herd of origin. The same was true for a black-faced sheep found positive at slaughter in 2021 that was traced back. The sheep was moved from another state without having official identification. These most recent untraceable cases illustrate the need for full compliance with the identification and recordkeeping regulations and for continued surveillance. It is essential that the sheep and goat industry, allied industry stakeholders (dealers, market, and slaughter plant personnel, etc.) and accredited veterinarians continue to be reminded of this message. To attain international recognition of scrapie freedom per the World Organization

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REPORT OF THE COMMITTEE

for Animal Health (WOAH), a country must demonstrate through an active surveillance program that no cases of scrapie have been detected in at least seven years. Surveillance needs to come from a variety of sources (e.g., farm, slaughter, etc.) and needs to be distributed across a country based on the population size of sheep and goats. The national scrapie surveillance goal for FY2023 is to collect at least 40,000 samples. The goal of collecting at least 40,000 samples has been in place for over a decade. Over the last years several factors including Covid and the highly pathogenic avian influenza (HPAI) outbreak have impacted the ability to meet this goal. The national target of at least 40,000 samples has not been met since FY2018. In FY2022, the total number of samples collected was about 21,000. Most states are meeting the minimum number of samples to retain their Consistent State status, however if every state met these minimum collection numbers, the total would only be 15,629. Rather than focusing just on meeting state minimums, surveillance needs to focus on meeting the national goal of at least 40,000. During FY2023 efforts will be made by APHIS-VS to work with State and industry partners to obtain more samples at slaughter, dealer feedlots, auctions, farms, veterinary diagnostic laboratories, and through veterinary referrals.

The low prevalence of scrapie requires additional surveillance efforts to detect the remaining cases such as increased targeted sampling which results in sampling subpopulations with a higher prevalence than the general population. VS conducted a formal expert elicitation to create a points system using an integrative group process to solicit input from seven experts with scrapie field experience. Taking into consideration the current scrapie status in the U.S. and practical considerations of running a scrapie surveillance program, VS developed a system to incentivize the submission of higher risk animals and animals from higher risk farms based on the expert elicited points system. Phase One of this system will be put in place in October 2023.

Delayed Incubation and Detection of Scrapie in G127S Goats

Dave Schneider, USDA, Agricultural Research Service (ARS)

Susceptibility of small ruminants to scrapie infection is influenced by genetic factors, most notably variations in the prion protein gene (PRNP) that result in certain amino acid substitutions in the prion protein (PrP). The prion research team at the Animal Disease Research Unit (ADRU) demonstrated goats bearing genetic variation in the PrP amino acid at position 222 (from Q to K, represented as Q222K) or at position 146 (N146S) were strongly resistant to developing infection after oral inoculation with classical scrapie. Tissues from the oldest surviving goats were checked for infectious prions by inoculating transgenic mice highly susceptible to scrapie prions (tg338 mice). Infectious prions were not detected in the tissues tested from goats heterozygous for this mutation (i.e., QK222). The two oldest NS126 goats were culled at the ages of 12 and 13 years of age without showing signs indicative of scrapie and without accumulation of the disease-associated misfolded prion protein (PrP-SC) in any tissue. Similar bioassay of these animals’ tissues in tg338 mice is underway.

An oral inoculation study to determine the effects of the G127S mutation in goats has been completed. The results demonstrate strong exposure was achieved since all GG127 goats (the fully susceptible genotype) became positive for PrP-Sc in most regulatory lymphoid tissues by 18 months of age. In most GG127 goats, accumulation of PrP-Sc in the obex was present at 24 months of age and all goats were culled with signs of classical scrapie by 36 months of age. PrP-Sc accumulation was also observed in GS127 goats, but which was greatly delayed. Distribution of PrP-Sc in regulatory lymphoid tissues was greatly reduced until 36 months of age, and accumulation in the obex was not observed until 36 months of age. Clinical signs of scrapie were not observed in any of the GS127 goats before the 36-month endpoint of the study. Three SS127 goats born during the study were also inoculated, two of which were recently euthanized having developed

215

SHEEP, GOATS AND CAMELIDS

clinical signs of scrapie at four and four and a half years of age. PrP-Sc accumulation was readily observed in the lymphoid tissues and obex of these two animals. The third SS127 goat remains healthy. Thus, S127 PrP in goats can support infection but appears to mediate slower disease kinetics even in heterozygous animals (i.e., GS127 goats), and which resulted in delayed detection in regulatory tissues.

Research Update from the National Animal Disease Center (NADC) Agricultural Research Service (ARS) Justin Greenlee, USDA-ARS

The Virus and Prion Research Unit at the National Animal Disease Center has ongoing research projects with the agents of scrapie, bovine spongiform encephalopathy, and chronic wasting disease (CWD). A project plan outlining the experiments for our four permanent scientists for the next five years was recently approved. The scrapie experiments in the plan are in two main categories: investigating atypical scrapie and the potential for the classical scrapie agent from goats to transmit to other species. The origin of bovine spongiform encephalopathy (BSE) in cattle is unknown, but it has been speculated that BSE came from the transmission of classical scrapie to cattle. Previous experiments conducted at the NADC and complimented by studies in the United Kingdom (UK) demonstrate that the lesions and molecular profile of PrPSc that result when the classical scrapie agent transmits to cattle are very different that BSE. However, recent studies demonstrate that when atypical scrapie prions are transmitted to mice expressing bovine prion protein the resulting PrPSc is indistinguishable from BSE. Therefore, we have initiated a study to investigate whether atypical scrapie prions will transmit to cattle and result in a BSE-like phenotype.

To investigate the transmission of classical scrapie prions from goats to other species we initiated studies in white-tailed deer and sheep. Whereas classical scrapie prions for sheep readily transmit to deer in an experimental setting, our recent work suggests that deer are not susceptible to classical scrapie prions from goats. Studies investigating the transmission of classical scrapie from goats to sheep are still underway, but early results suggest that transmission may be genotype dependent. Goat scrapie prions transmitted to 100% of ARQ/ARQ sheep exposed by the oronasal route. There was no evidence of PrPSc in VRQ/ARQ sheep tested after 70 months of incubation. Other genotypes of sheep are currently being studied.

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Chronic Wasting Disease (CWD) Alliance Update on CWD Information at an ARC GIS Secure International Data Management Hub

John Fischer and Matt Dunfee, Wildlife Management Institute (WMI)

With funding from a series of Multi-State Conservation Grants, the CWD Alliance, WMI, Association of Fish and Wildlife Agencies (AFWA), and DJ Case & Associates teamed up with the Departments of Natural Resources of Indiana, Michigan, and West Virginia to determine the greatest non-fiscal needs of wildlife management agency regarding CWD. Needs were identified through national surveys, personal interviews, and a workshop with wildlife professionals.

The greatest needs were CWD-related information items on a state and province basis. Consequently, four online, interactive mapping tools were developed to help document, track, and manage CWD. The maps are hosted at the CWD Alliance website (CWD-INFO.ORG). All of the maps are driven by a central data source reviewed and managed by state and provincial wildlife professionals.

The four maps are:

CWD in North America shows counties and wildlife management units in which CWD has been found in wild and/or captive cervids. It is available to everyone.

CWD-Related Hunting Regulations provides CWD-related regulations from every state and province. The map shows regulations, maps of CWD-positive areas, and the CWD regulatory status of each state and province. It is available to everyone.

Carcass Transport Regulations will help users learn the regulations impacting the transport of cervid carcasses from one state/province to another. It includes import, export, and pass-through regulations for cervid carcasses for every state and province. It is available to everyone.

222 REPORT OF THE COMMITTEE

Wildlife Agency Dashboard allows wildlife health and management professionals to research and compare CWD-related regulations or combinations of regulations across states/provinces.

The map is available to wildlife health and management professionals only and can be found at: https://cwd-info-collaboration-cwda.hub.arcgis.com/pages/ management. Editing and viewing-only access levels are available. If you would like access, contact Matt Dunfee mdunfee@wildlifemgt.org.

The maps are the first project and I encourage you to take a look at them. However, the capabilities of the hub are much broader, and we want to do more to assist you. We have heard about other problems that we know can be solved by the tools in the hub. We need you and your agencies to help us determine the biggest problems and the solutions to address CWD.

CWD Detection and Management: What Has Worked and Has Not?

In an effort to provide ongoing, authoritative, and defendable guidance on science based CWD management for state and provincial wildlife management agencies, WMI, the CWD Alliance, and the Association of Fish and Wildlife Agencies (AFWA) partnered on a project titled “National Coordination and Technical Assistance for the Prevention, Surveillance, and Management of Chronic Wasting Disease (CWD)”. This project was funded by the AFWA Multistate Conservation Grant program and was administrated by WMI. One of the objectives of this project was to document examples of CWD detection and management approaches that have thus far proven to be successful as well those that have been implemented unsuccessfully.

Reports of CWD detection and management actions were collected, reviewed, and summarized from five states affected by CWD in free-ranging cervids as were peer reviewed publications describing current management successes or lack thereof. All anecdotal reports and publications referenced in this document, or links to them, are provided in the appendix.

This review identifies management techniques that have effectively aided in early detection of CWD foci (and the agency response to them), reduced or stabilized CWD infection rates, or slowed the expansion of affected foci. These techniques are consistent with CWD management recommendations of the Association of Fish and Wildlife Agencies’ AFWA Best Management Practices for the Prevention, Surveillance, and Management of Chronic Wasting Disease and the Western Association of Fish and Wildlife Agencies’ Recommendations for Adaptive Chronic Wasting Disease Management in the West. The review also identifies management approaches that appear to have been unsuccessful.

Based upon the synthesis of the reports and publications included in this report, there appears to be general best practices that lead to greater success in managing CWD in wild cervids by state and provincial wildlife management agencies. These include, but are not limited to:

• Strong, cooperative, working relationships between state wildlife management and animal agriculture agencies that have or share regulatory authority over captive cervids.

• Rapid implementation of a previously prepared CWD response plan following the first CWD detection within a jurisdiction as well as subsequent detections in additional locations.

• Characterization of geographic distribution and CWD prevalence prior to determination of management approach(s).

223 WILDLIFE

• Designation of a CWD Management Zone with special restrictions and regulations under the authority of the state wildlife agency.

• A robust surveillance program capable of detecting CWD when prevalence is low, geographic distribution is limited, and the disease is more amenable to management.

• Effective public education programs that clearly state management goals while facilitating hunter and landowner support for, and compliance with, CWD-related actions, recommendations, regulations, and policies.

• A sustained and sustainable, long-term approach to CWD management, i.e., planning, funding, and implementing CWD management efforts for 10–20-year timelines.

• Harvest pressure and post-season culling that limit epidemic growth and are conducted over 10-20 year timelines.

In addition to the above successful management approaches, other factors were identified that appear to facilitate or contribute to the successes documented in the reports and publications:

• State wildlife agency authority over fenced, shooting facilities with mandatory testing of all animals that die within the enclosures.

• Mandatory participation in a state CWD Herd Certification program for intrastate movement of captive animals.

• Ability to compare and analyze data from several jurisdictions with differing harvest management practices over a long period of time (10-20 years).

• Aerial examination of newly detected areas to determine deer density and factors that confound CWD management such as artificial congregation of deer at baiting, feeding, mineral licks, or other sites.

• Availability of an agency CWD Response Team seven days a week to address concerns and interests of the public, landowners, and hunters.

• One-on-one agency staff interactions at CWD sampling stations to educate and inform hunters submitting animals for sampling.

• Quick turn-around on CWD test results (within three days after submission) to accommodate taxidermists and processors (and ensure their livelihoods) and hunters wishing to consume their venison.

• Participation and remuneration of taxidermists for collection of samples for CWD testing. The following issues were identified as likely contributors to the apparent failure of some CWD management programs:

• Surveillance programs for first detection of CWD within a jurisdiction that were too short-lived, sampled too few animals, or did not adequately cover the geographic area needed to conclusively determine disease absence.

• Use of inappropriate statistical tables in the analysis of surveillance data that falsely support a conclusion that CWD is absent within an area.

• Implementation of CWD management responses that failed due to inadequate characterization of the prevalence and geographic extent of a newly detected CWD focus.

• Management efforts were inadequate in scope and scale, were too short-lived, or management effort assessments were made too soon to detect measurable impacts in the target population.

224 REPORT OF THE COMMITTEE

CWD Alliance Applied CWD Research Program – 6 current projects Three projects were funded in 2019:

• Modeling Spatial Harvest Strategies for Chronic Wasting Disease Transmission – University of Alberta

• Prospective simulation assessments of alternative harvest strategies to mitigate and control CWD invasion and spread – University of Minnesota

• Accumulation of chronic wasting disease prions in plant tissues – University of Wisconsin

Three projects were funded in 2021:

• Population-level Impacts of Chronic Wasting Disease on Arkansas’s White-tailed Deer – AR Game and Fish Commission, University of Georgia, Southeastern Cooperative Wildlife Disease Study

• Mitigating CWD Prevalence in the Greater Wind River Mule Deer Population Through Harvest Management and Hotspot Identification – Wyoming Game and Fish, U.S. Fish and Wildlife Service, U.S. Geological Survey

• Punch in the Gut: Finding CWD Prions and Markers of Disease Risk in Fecal Samples – Cornell University

Funding for the 2021 projects included $222,239.60 from partners (Boone & Crockett Club, Rocky Mountain Elk Foundation, Mule Deer Foundation, and WMI), as well as $226,171 in matching funds from the recipient organizations. Thus, the total amount leveraged through our program for applied CWD research in 2021 was $448,410.60. Next round of funding is being assembled. How can we do more to help you? Please contact John Fischer (jfischer@uga.edu) or Matt Dunfee (mdunfee@wildlifemgt.org) with your ideas for applied research to benefit your state/region.

Committee Business:

A resolution titled, Chronic Wasting Disease Carcass Disposal Dumpster Management and Biosecurity, was presented and discussed. A motion was made by Charly Seale and seconded by Travis Lowe. A brief discussion of dumpsters management practices by states followed. The motion passed unanimously 18-0. 

snip...

World Organization for Animal Health (WOAH, formerly OIE) General Session 89 Update Gary Egrie, USDA-APHIS, Office of International Affairs Dr. Egrie gave an update on decisions taken during the WOAH 89th General Session (GS89) held in Paris, France on May 23-26, 2022. Nearly 500 participants from 151 countries participated either in person or virtually. Twenty-eight resolutions were adopted, and 70 international standards were updated. Chapters which were updated can be found on the United States Department of Agriculture (USDA) Animal and Plant Health Inspection Service (APHIS) Veterinary Services (VS) website. Of note, The Bovine Spongiform Encephalopathy (BSE) chapter underwent about three years of extensive review and comments, including input from the United States Government (U.S.), and the changes proposed would have altered the points-based approach countries have been following to monitor for BSE, to a risk-based surveillance program. Enough countries expressed concern that such a risk-based approach would be a more costly program to operate, or that the chapter did not include explicit language regarding a ruminant-to-ruminant feed-ban, that the chapter was withdrawn from consideration for adoption at GS89. The U.S. government interpretation of the changes proposed is that the new risk-based surveillance would be less costly, and non-adoption of the chapter highlights the need for further engagement with member countries to help clarify and explain the benefits of the proposed changes. Also of note, was the election of Dr. Rosemary Sifford, the APHIS Veterinary Services Deputy Administrator and the Delegate to the WOAH, as the Secretary General of the Executive Board of the Regional Commission of the Americas. This board represents the 32 countries of the Region of the Americas. Dr. Sifford being on the Executive Board offers the USA an opportunity to drive issues of importance to the USA in the Region and globally. Dr. Egrie also discussed a recent memorandum of understanding (MOU) signed between the WOAH and the United Nations Environment Program (UNEP).

snip...


2023-2023 TSE PRION UPDATE

PLEASE NOTE, USDA ET AL ONLY TESTING <25k CATTLE FOR MAD COW DISEASE, woefully inadequate, yet USDA just documented a case Atypical L-Type BSE, the most virulent strain to date...

Monday, May 22, 2023 

***> BSE TSE Prion MAD COW TESTING IN THE USA COMPARED TO OTHER COUNTRIES? 


Wednesday, May 24, 2023 

***> WAHIS, WOAH, OIE, United States of America Bovine spongiform encephalopathy Immediate notification




SATURDAY, MAY 20, 2023 

***> Tennessee State Veterinarian Alerts Cattle Owners to Disease Detection Mad Cow atypical L-Type BSE



MAY 19, 2023


2 weeks before the announcement of this recent mad cow case in the USA, i submitted this to the APHIS et al;

***> APPRX. 2 weeks before the recent mad cow case was confirmed in the USA, in Tennessee, atypical L-Type BSE, I submitted this to the APHIS et al;

Document APHIS-2023-0027-0001 BSE Singeltary Comment Submission May 2, 2023

''said 'burden' cost, will be a heavy burden to bear, if we fail with Bovine Spongiform Encephalopathy BSE TSE Prion disease, that is why this information collection is so critical''...



WEDNESDAY, NOVEMBER 08, 2023 

Ireland Atypical BSE confirmed November 3 2023 


TUESDAY, NOVEMBER 14, 2023 

Ireland Atypical BSE case, 3 progeny of case cow to be culled 


SUNDAY, JULY 16, 2023 

Switzerland Atypical BSE detected in a cow in the canton of St. Gallen 


WAHIS, WOAH, OIE, REPORT Switzerland Bovine Spongiform Encephalopathy Atypical L-Type

Switzerland Bovine Spongiform Encephalopathy Atypical L-Type

Switzerland - Bovine spongiform encephalopathy - Immediate notification



Monday, March 20, 2023 

WAHIS, WOAH, OIE, REPORT United Kingdom Bovine Spongiform Encephalopathy Atypical H-Type 





BRAZIL BSE START DATE 2023/01/18

BRAZIL BSE CONFIRMATION DATE 2023/02/22

BRAZIL BSE END DATE 2023/03/03



SPAIN BSE START DATE 2023/01/21

SPAIN BSE CONFIRMATION DATE 2023/02/03

SPAIN BSE END DATE 2023/02/06



NETHERLANDS BSE START DATE 2023/02/01

NETHERLANDS BSE CONFIRMATION DATE 2023/02/01

NETHERLANDS BSE END DATE 2023/03/13



PLEASE NOTE, USDA ET AL ONLY TESTING <25k CATTLE FOR MAD COW DISEASE, woefully inadequate, yet USDA just documented a case Atypical L-Type BSE, the most virulent strain to date...

Monday, May 22, 2023 

***> BSE TSE Prion MAD COW TESTING IN THE USA COMPARED TO OTHER COUNTRIES? 


THURSDAY, NOVEMBER 9, 2023 

EFSA Annual Report of the Scientific Network on BSE-TSE 2023


Annual Report of the Scientific Network on BSE-TSE 2023

European Food Safety Authority (EFSA

APPROVED: 25 October 2023


FRIDAY, JANUARY 20, 2023 

***> EPIDEMIOLOGY OF SCRAPIE IN THE UNITED STATES 


FRIDAY, NOVEMBER 25, 2022 

***> USA National Scrapie Eradication Program (NSEP) 2021 to 2003 A Year by Year Review


WEDNESDAY, FEBRUARY 03, 2021 

***> Scrapie TSE Prion United States of America a Review February 2021 Singeltary et al


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. 


2023 UPDATED SCIENCE ON TSE PRION TO DATE

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

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

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

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

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

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

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

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

=====end

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

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

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

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

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

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

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

Grant number: PCI2020-120680-2 ICRAD

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

=====end


Detection of classical BSE prions in asymptomatic cows after inoculation with atypical/Nor98 scrapie

Marina Betancor1, Belén Marín1, Alicia Otero1#, Carlos Hedman1, Antonio Romero2, Tomás Barrio3, Eloisa Sevilla1, Jean Yves Douet3, Alvina Huor3, Juan José Badiola1, Olivier Andréoletti3, Rosa Bolea1.

1Centro de Encefalopatías y Enfermedades Transmisibles Emergentes, Facultad de Veterinaria, Universidad de Zaragoza, Instituto Agroalimentario de Aragón - IA2, 50013, Zaragoza, Spain. 2 Servicio de Cirugía y Medicina Equina, Hospital Veterinario, Universidad de Zaragoza, 50013, Zaragoza, Spain 3 UMR École Nationale Vétérinaire de Toulouse (ENVT) - Institut National pour l’Agriculture, l’Alimentation et l’Environnement (INRAE) - 1225 Interactions Hôtes Agents Pathogènes (IHAP), 31300 Toulouse, France.

Aims: The emergence of bovine spongiform encephalopathy (BSE) prions from atypical scrapie has been recently proved in rodent and swine models. This study aimed to assess whether the inoculation of atypical scrapie could induce BSE-like disease in cattle.

Materials and Methods: Four calves were intracerebrally challenged with atypical scrapie. Animals were euthanized without clinical signs of prion disease between 7.2 and 11.3 years post-inoculation and tested for the accumulation of prions by conventional techniques and protein misfolding cyclic amplification (PMCA).

Results: None of the bovines showed signs compatible with prion disease. In addition, all tested negative for PrPSc accumulation by immunohistochemistry and western blotting. However, an emergence of BSE-like prions was detected during in vitro propagation of brain samples from the inoculated animals.

Conclusions: These findings suggest that atypical scrapie may represent a potential source of BSE infection in cattle.

Funded by: This work was supported financially by the following Spanish and European Interreg grants: Ministerio de Ciencia, Innovación y Universidades (Spanish Government), cofunded by Agencia Estatal de Investigación and the European Union and POCTEFA, which was 65% co-financed by the European Regional Development Fund (ERDF) through the Interreg V-A Spain-France-Andorra program (POCTEFA 2014– 2020).

Grant number: n° PID2021-125398OB-I00, EFA148/16 REDPRION

Acknowledgement: The authors would like to thank Sandra Felices and Daniel Romanos for their excellent technical assistance. Authors would also like to acknowledge the use of Servicio General de Apoyo a la Investigación-SAI, Universidad de Zaragoza

=====

Evolution of Nor98/ Atypical scrapie by iterative propagation in a homologous ovine PrPC context

Sara Canoyra1, Alba Marín-Moreno1, Juan Carlos Espinosa1, Natalia Fernández-Borges1, Nuria Jerez-Garrido1, Sylvie L. Benestad2, Enric Vidal3, Leonor Orge4, Olivier Andreoletti5 and Juan María Torres1.

1Centro de Investigación en Sanidad Animal, CISA-INIA-CSIC, Madrid, Spain. 2Norwegian Veterinary Institute, Ås, Norway. 3Centre de Recerca en Sanitat Animal, Universitat Autònoma de Barcelona (UAB)–Institut de Recerca i Tecnologia Agroalimentàries, Barcelona, Spain. 4Laboratory of Pathology, National Institute for Agrarian and Veterinary Research, Oeiras, Portugal 5UMR Institut National de la Recherche Agronomique (INRA)/École Nationale Vétérinaire de Toulouse (ENVT), Interactions Hôtes Agents Pathogènes, Toulouse, France

Aims: Nor98/ Atypical scrapie (AS) is a prion disease that causes sporadic casesin sheep and goats. Previous studies have shown that the transmission of AS to otherspecies led to the emergence of new prion strains. In the bovine and porcine PrP, there has been reported the emergence of classical BSE prions (Huor et al., 2019, Espinosa et al., 2009, Marin et. al., 2021) and in the bank vole M109I-PrP context, a classical scrapie-like prion strain emerges(Pirisinu et al., 2022). In this study, we analysed the possible evolution of the AS prion within the same specie by modelling the transmission in a homologous ovine PrP context.

Materials and Methods: A panel of AS isolates with different genotypes and geographical origins both from sheep and goats were inoculated in the wild-type transgenic mice model (ARQ-PrP, Aguilar-Calvo et al., 2014).

Results: The isolates infect the ovine ARQ-PrP mice with homogeneous survival time and a complete attack rate. For several AS isolatesthe transmission led to the emergence of 19kDa (with BSE-like characteristics), 21kDa or atypical prions and mixtures of these agents.

Conclusions:

Iterative subpassages of AS isolates into transgenic mice carrying ovine PrP showed an emergence of classical prions during in vivo propagation. This could be caused by the coexistence of strains in the isolate or the evolution of the AS through propagation in the ovine PrP.

These results allow us to hypothesize whether atypical prions might be the origin of prion diversity, where atypical prions tend to acquire classical forms. These results are relevant to control the exposure of farmed animals and humans to AS.

Funded by: MCIN/AEI/ 10.13039/501100011033 Grant number: PID2019-105837RB-I00


Transmission of CH1641 in cattle

Jemma K. Thorne, Janet Hills, M. Carmen Garcia-Pelayo, Timm Konold, and John Spiropoulos

Pathology and Animal Sciences Department, Animal and Plant Health Agency, Addlestone, UK

Aims: Classical BSE (C-BSE) was first identified in UK in the 1980s and is the only TSE that has proven zoonotic potential. The emergence of C-BSE was associated with a change in rendering practices implying that prions were able to escape inactivation. However, the exact origin of C-BSE remains unknown to this date although several theories have been proposed. CH1641 is a type of scrapie that biochemically is most akin to BSE. In addition CH1641 is the only scrapie type that can transmit as efficiently as C-BSE to bovinised mice (tg110) suggesting that the agent can propagate with ease on a bovine PrP background in contrast to other scrapie strains. This study was designed to investigate the transmissibility of CH1641 into cattle and characterise the resulting phenotype.

Material and Methods: To examine the ability of CH1641 to transmit to cattle, 5 animals were inoculated intracerebrally with an ovine CH1641 source. The clinical status of the animals was monitored and when they developed neurological signs they were euthanised on welfare grounds. Another 5 cattle were inoculated intracerebrally with saline solution to serve as negative, age-matched controls. Disease status was confirmed postmortem by statutory testing (Immunohistochemistry and Western blot).

Results: All CH1641 inoculated animals succumbed to clinical TSE with incubation periods 609–654 days post inoculation (dpi). One negative control died at 37 dpi and was excluded from the analysis as an intercurrent death. The remaining negative controls were killed at predetermined points to age match the CH1641 challenged cattle; they all were TSE negative. Western blot analysis revealed that in some animals the agent retained a CH1641 signature whilst in others the molecular profile acquired properties resembling C-BSE. Immunohistochemical analysis showed a similar phenotypic spectrum.

Conclusions: These preliminary data suggest that transmission of CH1641 in cattle is efficient and it results in a variable disease phenotype. Further studies are currently ongoing and include inoculation of bovinised and ovinised mice to identify if the CH1641 agent changed biological properties upon transmission to cattle. Secondary passages in cattle to investigate if intraspecies transmission can alter further the properties of the agent forcing it to converge towards C-BSE are also under consideration.

Funded by: Defra

Grant number: SE1962

Acknowledgement: Pathology and Animal Science Department staff members for technical excellence


Conformational shift as the evolutionary mechanism for classical BSE emergence from atypical scrapie

Sara Canoyra, Alba Marín-Moreno, Juan Carlos Espinosa, Natalia Fernández- Borges, and Juan María Torres

Centro de Investigación en Sanidad Animal, CISA-INIA-CSIC, Valdeolmos, Madrid, Spain

Aims: New prion strains emerge when the prion conformational characteristics change during intra- or cross-species transmission. There are two main theories, non-mutually exclusive, that could explain this phenomenon: the ‘deformed templating’ and the ‘conformational selection model’. According to the ‘deformed templating’ or mutation model, when the prion is unable to replicate in a new host there is a shift to a new PrPSc conformation. On the other hand, the ‘conformational selection’ theory postulates that prion isolates are a conglomerate of conformations and during cross-species transmission the species barrier acts as a filter.

In previous studies, we showed the emergence of the bovine spongiform encephalopathy agent (C-BSE) due to the transmission of atypical scrapie (AS) onto bovine PrP. This work will elucidate the evolutionary dichotomy in the AS transmission, providing supporting evidence on the hypothesis of the origin of the epidemic C-BSE prion from AS.

Material and Methods: A panel of AS isolates with different genotypes and geographical distribution was analyzed. To differentiate between AS and C-BSE two strain typing features were used: thermostability and PMCA propagation. The AS isolates underwent a heat treatment of 98°C during 2 h and were amplified in vitro by PMCA in bovine PrPC substrate. The templating activity with or without heat was determine after 10 amplification rounds by western blot characterization.

In addition, we analyzed an artificial mixture of AS and C-BSE generated by diluting C- BSE in a constant amount of AS.

Results: We observed a drastic loss in the C-BSE emergence due to the heat treatment. The AS is a thermolabile prion. Hence, the inactivation of the AS conformers with the ability to shift the conformation will slow down the emergence of the C-BSE.

In contrast, when we analyzed the artificial mixture C-BSE prions emerge even with the heat treatment. Therefore, if the AS isolates had contained a minoritarian C-BSE conformer (defended by the conformational selection model) the emergence wouldn’t have been affected by the heat.

Conclusions: Mutation is the main evolutionary mechanism responsible for the C-BSE emergence. The species barrier forces the shift to a possible structure (C-BSE in this case) in a thermodynamically unfavorable process.

This discovery reenforces the origin hypothesis of the epidemic C-BSE as a contact of the cattle with feed contaminated with AS. Where the AS will evolve shifting to a C-BSE stable conformation. This also has implications in the control of farmed animals and humans’ exposure to the AS.

Funded by:/Grant number: Project PID2019-105837RB-I00 MCIN/ AEI /10.13039/501,100,011,033 Fundación La Marató de TV3 Enfermedades

==== 

Distribution of PrPCWD in tissues of CWD affected sika deer using RT-QuIC following experimental oral transmission

HJ Sohna, KJ Parka, YR Leea, HC Parka, and G Mitchellb

aForeign animal disease division (FADD), Animal and Plant Quarantine Agency (APQA), Gimcheon, Korea; bNational & OIE Reference Laboratory for Scrapie and CWD, Canadian Food Inspection Agency, Ottawa, Ontario, Canada

Aims: Chronic wasting disease (CWD) is the only prion disease affecting free-ranging animals, reported in North America, South Korea and Scandinavia. Unlike in most other prion diseases, CWD agents are shed in blood, saliva, urine and feces which most likely contributes to the horizontal transmission between cervid species. Using NaPTA precipitation and real-time quaking-induced conversion (NaPTA/RT-QuIC) or only RT-QuIC, we established an ultrasensitive detection method for PrPCWD in the various tissues and body fluids of CWD affected sika deer following experimental oral transmission.

Material and Methods: Two Sika deer were orally inoculated with a brain homogenate (5 g) prepared from a farmed Canadian elk with clinical CWD. Deer were euthanized due to intercurrent disease or following the development of signs consistent with terminal CWD.

An array of tissues was collected and stored frozen, and were tested for the presence of PrPCWD by RT-QuIC or NaPTA/RT-QuIC.

Results: Primary oral transmission of CWD from elk to sika deer occurred in all inoculated animals, and was detected by RT-QuIC. Consistent with other cervids in the terminal stages of CWD, pathological prions were distributed throughout the central nervous system and lymphoid tissues including spleen. PrPCWD was also detected in the urinary system (kidney, urinary bladder, urine), salivary system (salivary glands and saliva), heart and skin. Detection in the skin occurred after collagenase treatment, and PrPCWD in the urinary system was associated with renal nerve plexus.

Conclusions: CWD transmits efficiently from elk to sika deer via the oral route. Widespread detection of PrPCWDby RT-QuIC suggests that, similar to other cervid species, infectivity is distributed throughout a wide range of tissues in sika deer with clinical CWD.

Funded by: Animal and Plant Quarantine Agency

Grant number: B-154085-2022-24-01

''WD transmits efficiently from elk to sika deer via the oral route. Widespread detection of PrPCWDby RT-QuIC suggests that, similar to other cervid species, infectivity is distributed throughout a wide range of tissues in sika deer with clinical CWD.''

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9467582/

Ruminant feed ban for cervids in the United States ?

Posted by flounder on 31 Jan 2015 at 20:14 GMT

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 the USA, under the Food and Drug Administration’s BSE Feed Regulation (21 CFR 589.2000) most material (exceptions include milk, tallow, and gelatin) from deer and elk is prohibited for use in feed for ruminant animals. With regards to feed for non-ruminant animals, under FDA law, CWD positive deer may not be used for any animal feed or feed ingredients. For elk and deer considered at high risk for CWD, the FDA recommends that these animals do not enter the animal feed system. However, this recommendation is guidance and not a requirement by law. 

Animals considered at high risk for CWD include: 

1) animals from areas declared to be endemic for CWD and/or to be CWD eradication zones and 

2) deer and elk that at some time during the 60-month period prior to slaughter were in a captive herd that contained a CWD-positive animal. 

Therefore, in the USA, materials from cervids other than CWD positive animals may be used in animal feed and feed ingredients for non-ruminants. 

The amount of animal PAP that is of deer and/or elk origin imported from the USA to GB can not be determined, however, as it is not specified in TRACES. It may constitute a small percentage of the 8412 kilos of non-fish origin processed animal proteins that were imported from US into GB in 2011. 

Overall, therefore, it is considered there is a __greater than negligible risk___ that (nonruminant) animal feed and pet food containing deer and/or elk protein is imported into GB. 

There is uncertainty associated with this estimate given the lack of data on the amount of deer and/or elk protein possibly being imported in these products. 

snip... 

36% in 2007 (Almberg et al., 2011). In such areas, population declines of deer of up to 30 to 50% have been observed (Almberg et al., 2011). In areas of Colorado, the prevalence can be as high as 30% (EFSA, 2011). The clinical signs of CWD in affected adults are weight loss and behavioural changes that can span weeks or months (Williams, 2005). In addition, signs might include excessive salivation, behavioural alterations including a fixed stare and changes in interaction with other animals in the herd, and an altered stance (Williams, 2005). These signs are indistinguishable from cervids experimentally infected with bovine spongiform encephalopathy (BSE). Given this, if CWD was to be introduced into countries with BSE such as GB, for example, infected deer populations would need to be tested to differentiate if they were infected with CWD or BSE to minimise the risk of BSE entering the human food-chain via affected venison. 

snip... 

The rate of transmission of CWD has been reported to be as high as 30% and can approach 100% among captive animals in endemic areas (Safar et al., 2008). 

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... 

http://webarchive.nationa... 


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 


*** The potential impact of prion diseases on human health was greatly magnified by the recognition that interspecies transfer of BSE to humans by beef ingestion resulted in vCJD. While changes in animal feed constituents and slaughter practices appear to have curtailed vCJD, there is concern that CWD of free-ranging deer and elk in the U.S. might also cross the species barrier. Thus, consuming venison could be a source of human prion disease. Whether BSE and CWD represent interspecies scrapie transfer or are newly arisen prion diseases is unknown. Therefore, the possibility of transmission of prion disease through other food animals cannot be ruled out. There is evidence that vCJD can be transmitted through blood transfusion. There is likely a pool of unknown size of asymptomatic individuals infected with vCJD, and there may be asymptomatic individuals infected with the CWD equivalent. These circumstances represent a potential threat to blood, blood products, and plasma supplies. 


''There are no known familial or genetic TSEs of animals, although polymorphisms in the PRNP gene of some species (sheep for example) may influence the length of the incubation period and occurrence of disease.'' 

c) The commonest form of CJD occurs as a sporadic disease, the cause of which is unknown, although genetic factors (particularly the codon 129 polymorphism in the prion protein gene (PRNP)) influence disease susceptibility. The familial forms of human TSEs (see Box 1) appear to have a solely genetic origin and are closely associated with mutations or insertions in the PRNP gene. Most, but not all, of the familial forms of human TSEs have been transmitted experimentally to animals. There are no known familial or genetic TSEs of animals, although polymorphisms in the PRNP gene of some species (sheep for example) may influence the length of the incubation period and occurrence of disease.


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

In the USA, under the Food and Drug Administration’s BSE Feed Regulation (21 CFR 589.2000) most material (exceptions include milk, tallow, and gelatin) from deer and elk is prohibited for use in feed for ruminant animals. With regards to feed for non-ruminant animals, under FDA law, CWD positive deer may not be used for any animal feed or feed ingredients. For elk and deer considered at high risk for CWD, the FDA recommends that these animals do not enter the animal feed system. 

***However, this recommendation is guidance and not a requirement by law. 

================================= 

Draft Guidance on Use of Material From Deer and Elk in Animal Feed; CVM Updates on Deer and Elk Withdrawn FDA Veterinarian Newsletter July/August 2003 Volume XVIII, No 4

FDA has announced the availability of a draft guidance for industry entitled “Use of Material from Deer and Elk in Animal Feed.” This draft guidance document (GFI #158), when finalized, will describe FDA’s current thinking regarding the use in animal feed of material from deer and elk that are positive for Chronic Wasting Disease (CWD) or that are at high risk for CWD.

CWD is a neurological (brain) disease of farmed and wild deer and elk that belong in the cervidae animal family (cervids). Only deer and elk are known to be susceptible to CWD by natural transmission. The disease has been found in farmed and wild mule deer, white-tailed deer, North American elk, and farmed black-tailed deer. CWD belongs to a family of animal and human diseases called transmissible spongiform encephalopathies (TSEs). TSEs are very rare, but are always fatal.

This draft Level 1 guidance, when finalized, will represent the Agency’s current thinking on the topic. It does not create or confer any rights for or on any person and does not operate to bind FDA or the public. An alternate method may be used as long as it satisfies the requirements of applicable statutes and regulations.

Draft guidance #158 is posted on the FDA/Center for Veterinary Medicine Home Page. Single copies of the draft guidance may be obtained from the FDA Veterinarian.

- - Page Last Updated: 04/16/2013 

http://www.fda.gov/Animal... 


CONTAINS NON-BINDING RECOMMENDATIONS

158

Guidance for Industry

Use of Material from Deer and Elk in Animal Feed

Comments and suggestions regarding the document should be submitted to Division of Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852. Submit electronic comments to http://www.regulations.go.... All comments should be identified with the Docket No. 03D-0186.

For questions regarding this guidance, contact Burt Pritchett, Center for Veterinary Medicine (HFV- 222), Food and Drug Administration, 7519 Standish Place, Rockville, MD 20855, 240-453-6860, E-mail: burt.pritchett@fda.hhs.gov . Additional copies of this guidance document may be requested from the Communications Staff (HFV-12), Center for Veterinary Medicine, Food and Drug Administration, 7519 Standish Place, Rockville, MD 20855, and may be viewed on the Internet at http://www.fda.gov/Animal....

U.S. Department of Health and Human Services

Food and Drug Administration Center for Veterinary Medicine September 15, 2003

CONTAINS NON-BINDING RECOMMENDATIONS

158

Guidance for Industry1

Use of Material from Deer and Elk in Animal Feed

This guidance represents the Food and Drug Administration’s current thinking on the use of material from deer and elk in animal feed. It does not create or confer any rights for or on any person and does not operate to bind FDA or the public. You can use an alternative approach if the approach satisfies the requirements of applicable statutes or regulations. If you want to discuss an alternative approach, contact the FDA staff responsible for implementing this guidance. If you cannot identify the appropriate FDA staff, call the appropriate number listed on the title page of this guidance. 

I. Introduction 

FDA’s guidance documents, including this guidance, do not establish legally enforceable responsibilities. Instead, guidances describe the Agency’s current thinking on a topic and should be viewed only as recommendations, unless specific regulatory or statutory requirements are cited. The use of the word “should” in Agency guidances means that something is suggested or recommended, but not required. 

Under FDA’s BSE feed regulation (21 CFR 589.2000) most material from deer and elk is prohibited for use in feed for ruminant animals. This guidance document describes FDA’s recommendations regarding the use in all animal feed of all material from deer and elk that are positive for Chronic Wasting Disease (CWD) or are considered at high risk for CWD. The potential risks from CWD to humans or non-cervid animals such as poultry and swine are not well understood. However, because of recent recognition that CWD is spreading rapidly in white-tailed deer, and because CWD’s route of transmission is poorly understood, FDA is making recommendations regarding the use in animal feed of rendered materials from deer and elk that are CWD-positive or that are at high risk for CWD.

II. Background

CWD is a neurological (brain) disease of farmed and wild deer and elk that belong in the animal family cervidae (cervids). Only deer and elk are known to be susceptible to CWD by natural transmission. The disease has been found in farmed and wild mule deer,

1 This guidance has been prepared by the Division of Animal Feeds in the Center for Veterinary Medicine (CVM) at the Food and Drug Administration.

1

CONTAINS NON-BINDING RECOMMENDATIONS

2

white-tailed deer, North American elk, and in farmed black-tailed deer. CWD belongs to a family of animal and human diseases called transmissible spongiform encephalopathies (TSEs). These include bovine spongiform encephalopathy (BSE or “mad cow” disease) in cattle; scrapie in sheep and goats; and classical and variant Creutzfeldt-Jakob diseases (CJD and vCJD) in humans. There is no known treatment for these diseases, and there is no vaccine to prevent them. In addition, although validated postmortem diagnostic tests are available, there are no validated diagnostic tests for CWD that can be used to test for the disease in live animals.

III.

Use in animal feed of material from CWD-positive deer and elk

Material from CWD-positive animals may not be used in any animal feed or feed ingredients. Pursuant to Sec. 402(a)(5) of the Federal Food, Drug, and Cosmetic Act, animal feed and feed ingredients containing material from a CWD-positive animal would be considered adulterated. FDA recommends that any such adulterated feed or feed ingredients be recalled or otherwise removed from the marketplace.

IV.

Use in animal feed of material from deer and elk considered at high risk for CWD

Deer and elk considered at high risk for CWD include: (1) animals from areas declared by State officials to be endemic for CWD and/or to be CWD eradication zones; and (2) deer and elk that at some time during the 60-month period immediately before the time of slaughter were in a captive herd that contained a CWD-positive animal.

FDA recommends that materials from deer and elk considered at high risk for CWD no longer be entered into the animal feed system. Under present circumstances, FDA is not recommending that feed made from deer and elk from a non-endemic area be recalled if a State later declares the area endemic for CWD or a CWD eradication zone. In addition, at this time, FDA is not recommending that feed made from deer and elk believed to be from a captive herd that contained no CWD-positive animals be recalled if that herd is subsequently found to contain a CWD-positive animal. V. Use in animal feed of material from deer and elk NOT considered at high risk for CWD

FDA continues to consider materials from deer and elk NOT considered at high risk for CWD to be acceptable for use in NON-RUMINANT animal feeds in accordance with current agency regulations, 21 CFR 589.2000. Deer and elk not considered at high risk include: (1) deer and elk from areas not declared by State officials to be endemic for CWD and/or to be CWD eradication zones; and (2) deer and elk that were not at some time during the 60-month period immediately before the time of slaughter in a captive herd that contained a CWD-positive animal. 


that voluntary mad cow feed ban that became law, how did that work out for us $ 

***e) "Big Jim's" BBB Deer Ration, Big Buck Blend, Recall # V-104-6; ***

ENFORCEMENT REPORT FOR AUGUST 2, 2006 

please note, considering .005 grams is lethal, I do not know how much of this 125 TONS of banned mad cow protein was part of the ;

e) "Big Jim's" BBB Deer Ration, Big Buck Blend, Recall # V-104-6; 

bbbut, this was about 10 years post mad cow feed ban from 1997. 10 years later, and still feeding banned mad cow protein to cervids??? 

considering that .005 gram is lethal to several bovines, and we know that the oral consumption of CWD tainted products is very efficient mode of transmission of CWD. 

Subject: MAD COW FEED RECALL AL AND FL VOLUME OF PRODUCT IN COMMERCE 125 TONS Products manufactured from 02/01/2005 until 06/06/2006 

Date: August 6, 2006 at 6:16 pm PST 

PRODUCT 

a) CO-OP 32% Sinking Catfish, Recall # V-100-6; 

b) Performance Sheep Pell W/Decox/A/N, medicated, net wt. 50 lbs, Recall # V-101-6; 

c) Pro 40% Swine Conc Meal -- 50 lb, Recall # V-102-6; 

d) CO-OP 32% Sinking Catfish Food Medicated, Recall # V-103-6; 

***e) "Big Jim's" BBB Deer Ration, Big Buck Blend, Recall # V-104-6; ***

f) CO-OP 40% Hog Supplement Medicated Pelleted, Tylosin 100 grams/ton, 50 lb. bag, Recall # V-105-6; 

g) Pig Starter Pell II, 18% W/MCDX Medicated 282020, Carbadox -- 0.0055%, Recall # V-106-6; 

h) CO-OP STARTER-GROWER CRUMBLES, Complete Feed for Chickens from Hatch to 20 Weeks, Medicated, Bacitracin Methylene Disalicylate, 25 and 50 Lbs, Recall # V-107-6; 

i) CO-OP LAYING PELLETS, Complete Feed for Laying Chickens, Recall # 108-6; 

j) CO-OP LAYING CRUMBLES, Recall # V-109-6; 

k) CO-OP QUAIL FLIGHT CONDITIONER MEDICATED, net wt 50 Lbs, Recall # V-110-6; 

l) CO-OP QUAIL STARTER MEDICATED, Net Wt. 50 Lbs, Recall # V-111-6; 

m) CO-OP QUAIL GROWER MEDICATED, 50 Lbs, Recall # V-112-6 

CODE 

Product manufactured from 02/01/2005 until 06/06/2006 

RECALLING FIRM/MANUFACTURER 

Alabama Farmers Cooperative, Inc., Decatur, AL, by telephone, fax, email and visit on June 9, 2006. FDA initiated recall is complete. 

REASON 

Animal and fish feeds which were possibly contaminated with ruminant based protein not labeled as "Do not feed to ruminants". 

VOLUME OF PRODUCT IN COMMERCE 

125 tons 

DISTRIBUTION 

AL and FL 

END OF ENFORCEMENT REPORT FOR AUGUST 2, 2006 

### 

http://www.fda.gov/Safety... 

http://web.archive.org/web/20100120023832/http://www.fda.gov/Safety/Recalls/EnforcementReports/2006/ucm120413.htm


How in the hell do you make a complete recall of 27,694,240 lbs of feed that was manufactured from materials that may have been contaminated with mammalian protein, in one state, Michigan, 2006? Wonder how much was fed out?

RECALLS AND FIELD CORRECTIONS: VETERINARY MEDICINE -- CLASS II

______________________________

PRODUCT

a) CO-OP 32% Sinking Catfish, Recall # V-100-6; b) Performance Sheep Pell W/Decox/A/N, medicated, net wt. 50 lbs, Recall # V-101-6; c) Pro 40% Swine Conc Meal -- 50 lb, Recall # V-102-6; d) CO-OP 32% Sinking Catfish Food Medicated, Recall # V-103-6; e) "Big Jim’s" BBB Deer Ration, Big Buck Blend, Recall # V-104-6; f) CO-OP 40% Hog Supplement Medicated Pelleted, Tylosin 100 grams/ton, 50 lb. bag, Recall # V-105-6; g) Pig Starter Pell II, 18% W/MCDX Medicated 282020, Carbadox -- 0.0055%, Recall # V-106-6; h) CO-OP STARTER-GROWER CRUMBLES, Complete Feed for Chickens from Hatch to 20 Weeks, Medicated, Bacitracin Methylene Disalicylate, 25 and 50 Lbs, Recall # V-107-6; i) CO-OP LAYING PELLETS, Complete Feed for Laying Chickens, Recall # 108-6; j) CO-OP LAYING CRUMBLES, Recall # V-109-6; k) CO-OP QUAIL FLIGHT CONDITIONER MEDICATED, net wt 50 Lbs, Recall # V-110-6; l) CO-OP QUAIL STARTER MEDICATED, Net Wt. 50 Lbs, Recall # V-111-6; m) CO-OP QUAIL GROWER MEDICATED, 50 Lbs, Recall # V-112-6

CODE Product manufactured from 02/01/2005 until 06/06/2006

RECALLING FIRM/MANUFACTURER Alabama Farmers Cooperative, Inc., Decatur, AL, by telephone, fax, email and visit on June 9, 2006. FDA initiated recall is complete.

REASON Animal and fish feeds which were possibly contaminated with ruminant based protein not labeled as "Do not feed to ruminants".

VOLUME OF PRODUCT IN COMMERCE 125 tons

DISTRIBUTION AL and FL

______________________________

PRODUCT Bulk custom dairy feds manufactured from concentrates, Recall # V-113-6

CODE All dairy feeds produced between 2/1/05 and 6/16/06 and containing H. J. Baker recalled feed products.

RECALLING FIRM/MANUFACTURER Vita Plus Corp., Gagetown, MI, by visit beginning on June 21, 2006. Firm initiated recall is complete.

REASON The feed was manufactured from materials that may have been contaminated with mammalian protein.

VOLUME OF PRODUCT IN COMMERCE 27,694,240 lbs

DISTRIBUTION MI

______________________________

PRODUCT Bulk custom made dairy feed, Recall # V-114-6

CODE None

RECALLING FIRM/MANUFACTURER Burkmann Feeds LLC, Glasgow, KY, by letter on July 14, 2006. Firm initiated recall is ongoing.

REASON Custom made feeds contain ingredient called Pro-Lak, which may contain ruminant derived meat and bone meal.

VOLUME OF PRODUCT IN COMMERCE ?????

DISTRIBUTION KY

END OF ENFORCEMENT REPORT FOR AUGUST 2, 2006

###


Monday, November 13, 2023

Food and Drug Administration's BSE Feed Regulation (21 CFR 589.2000) Singeltary Another Request for Update 2023


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. 

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

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

Funded by: Wisconsin Department of Natural Resources


CWD TSE PRION CERVID ENVIRONMENTAL RISK FACTORS 2023

"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.

Results: We are able to detect prion seeding activity at multiple types of environmental hotspots, including carcass sites, contaminated captive facilities, and scrapes (i.e. urine and saliva). Differences in relative prion concentration vary depending on the nature and source of the contamination.

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

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

Funded by: Wisconsin Department of Natural Resources

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

=====end

***> 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


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.


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


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

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

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


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.


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

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


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


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


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


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


THURSDAY, FEBRUARY 28, 2019 

BSE infectivity survives burial for five years with only limited spread


CWD TSE PRION CERVID ENVIRONMENTAL RISK FACTORS 2023

So, this is what we leave our children and grandchildren?..

"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

Results: We are able to detect prion seeding activity at multiple types of environmental hotspots, including carcass sites, contaminated captive facilities, and scrapes (i.e. urine and saliva). Differences in relative prion concentration vary depending on the nature and source of the contamination. Additionally, we have determined that prion seeding activity is retained for at least fifteen years at a contaminated site following attempted remediation. Conclusions: Detection of prions in the environment is of the utmost importance for controlling chronic wasting disease spread. Here, we have demonstrated a viable method for detection of prions in complex environmental matrices. However, it is quite likely that this method underestimates the total infectious prion load in a contaminated sample, due to incomplete recovery of infectious prions. Further refinements are necessary for accurate quantification of prions in such samples, and to account for the intrinsic heterogeneities found in the broader environment.

=====end

Prion 2023 Abstracts


***> 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 


Rapid recontamination of a farm building occurs after attempted prion removal First 

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

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

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

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


***>This is very likely to have parallels with control efforts for CWD in cervids. https://pubmed.ncbi.nlm.nih.gov/30602491/ 

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. 


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.


Plants as vectors for environmental prion transmission

Published:November 09, 2023DOI:https://doi.org/10.1016/j.isci.2023.108428

Advertisement Highlights

• Abnormal prion protein can enter the roots of plants

• Plants can translocate detectable levels of prions to aerial tissues

•Animals exposed to prion-contaminated plant tissues can acquire disease

•Contaminated plants may represent a route of prion exposure 

Snip…

Nonetheless, our finding of accumulation of two prion strains by a variety of plants grown hydroponically, in agar, or on soil supports the potential for plants to acquire CWD, scrapie, or other prions from the environment and transmit prion disease to susceptible hosts, making plants a plausible vector for prion diseases in wildlife, livestock, and humans. The potential for plants to serve as vectors for prion disease has implications for the disposal of infected carcasses, grazing practices, and the use and transport of potentially contaminated crop materials.



Carrot plants as potential vectors for CWD transmission. 

The PMCA analysis demonstrated CWD seeding activity in soils contaminated with CWD prions and in carrot plants (leaves and roots) grown on them. Bioassays showed that both plants and roots contained CWD prions sufficiently to induce disease. As expected, animals treated with prion-infected soils developed prion disease at shorter incubation periods (and complete attack rates) compared to plant components. We show that edible plant components can absorb prions from CWD-contaminated soils and transport them to their aerial parts. Our results indicate that edible plants could participate as vectors of CWD transmission. 


“In addition, hay and straw from the United States and Canada must be accompanied by a certificate from a public veterinarian that the product has been harvested in states or provinces where Chronic Wasting Disease has not been detected on deer.”

Regulation No. 1599 of 2018 on additional requirements for the import of hay and straw for used for animal feed.

Country Norway

Type of law Regulation

Source

FAO , FAOLEX

In addition, hay and straw from the United States and Canada must be accompanied by a certificate from a public veterinarian that the product has been harvested in states or provinces where Chronic Wasting Disease has not been detected on deer.


CWD, Real Estate and Property evaluations ?$?$?$ 

Experimental transmission of the chronic wasting disease agent to swine after oral or intracranial inoculation

Running Title: The chronic wasting disease agent transmits to swine

S. Jo Moore1,2 , M. Heather West Greenlee3 , Naveen Kondru3 , Sireesha Manne3 , Jodi D. Smith1,# , Robert A. Kunkle1 , Anumantha Kanthasamy3 , Justin J. Greenlee1*

Virus and Prion Research Unit, National Animal Disease Center, USDA, Agricultural Research Service, Ames, Iowa, United States of America

Oak Ridge Institute for Science and Education, Oak Ridge, Tennessee, United States of America

Department of Biomedical Sciences, Iowa State University College of Veterinary Medicine, Ames, Iowa, United States of America

Current Address: Department of Veterinary Pathology, Iowa State University College of Veterinary Medicine, Ames, Iowa, United States of America * Corresponding author Email: justin.greenlee@ars.usda.gov

JVI Accepted Manuscript Posted Online 12 July 2017 J. Virol. doi:10.1128/JVI.00926-17

This is a work of the U.S. Government and is not subject to copyright protection in the United States. Foreign copyrights may apply.

 on July 27, 2017 by guest http://jvi.asm.org/ Downloaded from

Abstract

Chronic wasting disease (CWD) is a naturally occurring, fatal neurodegenerative disease of cervids. The potential for swine to serve as a host for the agent of chronic wasting 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 . Crossbred piglets were assigned to one of three groups: intracranially inoculated (n=20), orally inoculated (n=19), or non -inoculated (n=9). At approximately the age at which commercial pigs reach market weight, half of the pigs in each group were culled (‘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 western blotting (WB), antigen -capture immunoassay (EIA), immunohistochemistry (IHC) and in vitro real -time quaking induced conversion (RT -QuIC). Brain samples from selected pigs were also bioassayed in mice expressing porcine prion protein. Four intracranially inoculated aged pigs and one orally inoculated aged pig were positive by EIA, IHC and/or WB. Using RT -QuIC, PrPSc was detected in lymphoid and/or brain tissue from one or more pigs in each inoculated group. Bioassay was positive in 4 out of 5 pigs assayed.

This study demonstrates that pigs can support low-level amplification of CWD prions, although the species barrier to CWD infection is relatively high. However, 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.

Discussion

snip...

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

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


cwd scrapie pigs oral routes 

***> However, at 51 months of incubation or greater, 5 animals were positive by one or more diagnostic methods. Furthermore, positive bioassay results were obtained from all inoculated groups (oral and intracranial; market weight and end of study) suggesting that swine are potential hosts for the agent of scrapie. <*** 

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

***> Results: PrPSc was not detected by EIA and IHC in any RPLNs. All tonsils and MLNs were negative by IHC, though the MLN from one pig in the oral <6 month group was positive by EIA. PrPSc was detected by QuIC in at least one of the lymphoid tissues examined in 5/6 pigs in the intracranial <6 months group, 6/7 intracranial >6 months group, 5/6 pigs in the oral <6 months group, and 4/6 oral >6 months group. Overall, the MLN was positive in 14/19 (74%) of samples examined, the RPLN in 8/18 (44%), and the tonsil in 10/25 (40%). 

***> Conclusions: This study demonstrates that PrPSc accumulates in lymphoid tissues from pigs challenged intracranially or orally with the CWD agent, and can be detected as early as 4 months after challenge. CWD-infected pigs rarely develop clinical disease and if they do, they do so after a long incubation period. This raises the possibility that CWD-infected pigs could shed prions into their environment long before they develop clinical disease. Furthermore, lymphoid tissues from CWD-infected pigs could present a potential source of CWD infectivity in the animal and human food chains. 




Conclusions: This study demonstrates that PrPSc accumulates in lymphoid tissues from pigs challenged intracranially or orally with the CWD agent, and can be detected as early as 4 months after challenge. CWD-infected pigs rarely develop clinical disease and if they do, they do so after a long incubation period. This raises the possibility that CWD-infected pigs could shed prions into their environment long before they develop clinical disease. Furthermore, lymphoid tissues from CWD-infected pigs could present a potential source of CWD infectivity in the animal and human food chains.


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


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. ...


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.


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. ...


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. ...


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


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.....


BSE--U.S. 50 STATE CONFERENCE CALL Jan. 9, 2001

Date: Tue, 9 Jan 2001 16:49:00 -0800

From: "Terry S. Singeltary Sr."

Reply-To: Bovine Spongiform Encephalopathy

To: BSE-L@uni-karlsruhe.de 


The Mad Cow That Stole Christmas, 2003-2023

The Mad Cow That Stole Christmas, 20 Years Later

The Mad Cow That Stole Christmas, 20 Years Later, What Has Changed, Nothing

THE USA has systematically covered up mad cow disease, in my honest opinion, the USA mad cow disease today, is Chronic Wasting Disease CWD TSE Prion disease in Cervid, they can't cover that up.

before going any further, while reading this, remember one thing, the mad cow feed ban has failed terribly, along with surveillance efforts to detect BSE. only testing <25K cattle in the USA every year, you will not find BSE, this was said long ago, you must test at least 40K, and yet that, will not find much.

1st, let's review the old history of this first case of mad cow disease in the USA, that mad cow that stole Christmas in 2003, shall we...


Why is USDA "only" testing 25,000 samples a year?

USDA's surveillance strategy is to focus on the targeted populations where we are most likely to find disease if it is present. This is the most effective way to meet both OIE and our domestic surveillance standards. After completing our enhanced surveillance in 2006 and confirming that our BSE prevalence was very low, an evaluation of the program showed that reducing the number of samples collected to 40,000 samples per year from these targeted, high risk populations would allow us to continue to exceed these standards. In fact, the sampling was ten times greater than OIE standards. A subsequent evaluation of the program in 2016 using data collected over the past 10 years showed that the surveillance standards could still be met with a further reduction in the number of samples collected by renderers and 3D/4D establishments which have a very low OIE point value because the medical history of these animals is usually unknown. Therefore, in 2016, the number of samples to be tested was reduced to 25,000 where it remains today.


Bottom line, you don’t test, you don’t find$ FRIDAY, MAY 19, 2023 

USDA Announces Atypical L-Type Bovine Spongiform Encephalopathy BSE Detection

 

SATURDAY, MAY 20, 2023 

Tennessee State Veterinarian Alerts Cattle Owners to Disease Detection Mad Cow atypical L-Type BSE



Wednesday, May 24, 2023 

WAHIS, WOAH, OIE, United States of America Bovine spongiform encephalopathy Immediate notification


ABOUT 2+ WEEKS BEFORE THE DETECTION OF BSE IN THE USA IN 2023, I WROTE THIS;

May 2, 2023, i submitted this to the USDA et al;

Docket No. APHIS–2023–0027 Notice of Request for Revision to and Extension of Approval of an Information Collection; National Veterinary Services Laboratories; Bovine Spongiform Encephalopathy Surveillance Program Singeltary Submission

ONLY by the Grace of God, have we not had a documented BSE outbreak, that and the fact the USDA et al are only testing 25K cattle for BSE, a number too low to find mad cow disease from some 28.9 million beef cows in the United States as of Jan. 1, 2023, down 4% from last year. The number of milk cows in the United States increased to 9.40 million. U.S. calf crop was estimated at 34.5 million head, down 2% from 2021. Jan 31, 2023. 

ALL it would take is one BSE positive, yet alone a handful of BSE cases, this is why the Enhanced BSE was shut down, and the BSE testing shut down to 25k, and the BSE GBRs were replaced with BSE MRRs, after the 2003 Christmas Mad cow, the cow that stole Christmas, making it legal to trade BSE, imo. 

Document APHIS-2023-0027-0001 BSE Singeltary Comment Submission


see full submission;



FRIDAY, DECEMBER 08, 2023 

TEXAS CWD TSE PRION DIRE CONSEQUENCES ARE HERE! 


CWD TO HUMANS, ZOONOSIS, ZOONOTIC, POTENTIAL, OR HAS IT ALREADY HAPPENED?

***> 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

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.


Generation of human chronic wasting disease in transgenic mice

Zerui Wanga, Kefeng Qinb, Manuel V. Camachoa, Ignazio Cali a,c, Jue Yuana, Pingping Shena, Tricia Gillilanda, Syed Zahid Ali Shaha, Maria Gerasimenkoa, Michelle Tanga, Sarada Rajamanickama, Anika Yadatia, Lawrence B. Schonbergerd, Justin Greenleee, Qingzhong Konga,c, James A. Mastriannib, and Wen-Quan Zoua,c

aDepartment of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH, USA; bDepartment of Neurology and Center for Comprehensive Care and Research on Memory Disorders, the University of Chicago Pritzker School of Medicine, Chicago, USA; cNational Prion Disease Pathology Surveillance Center, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA; dDivision of High-Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, 1600 Clifton Rd, Atlanta, GA, USA; eVirus and Prion Research Unit, National Animal Disease Center, USDA, Agricultural Research Service, 1920 Dayton Avenue, Ames, IA, USA

Aims: Chronic wasting disease (CWD) results from the accumulation of an infectious misfolded conformer (PrPSc) of cellular prion protein (PrPC) in the brains of deer and elk. It has been spreading rapidly throughout many regions of North America, exported inadvertently to South Korea, and more recently identified in Europe. Mad cow disease has caused variant Creutzfeldt-Jakob disease (vCJD) in humans and is currently the only known zoonotic prion disease. Whether CWD is transmissible to humans remains uncertain. The aims of our study were not only to confirm whether CWD prion isolates can convert human brain PrPC into PrPSc in vitro by serial protein misfolding cyclic amplification (sPMCA) but also to determine whether the sPMCA-induced CWD-derived human PrPScis infectious.

Material and Methods: Eight CWD prion isolates from 7 elks and 1 deer were used as the seeds while normal human brain homogenates containing either PrP-129 MM (n = 2) or PrP-129 VV (n = 1) were used as the substrates for sPMCA assay. A normal elk brain tissue sample was used as a negative control seed. Two lines of humanized transgenic (Tg) mice expressing either human PrP-129VV or −129 MM polymorphism were included for transmission studies to determine the infectivity of PMCA-amplified PrPSc. Wester blotting and immunohistochemistry and hematoxylin & eosin staining were used for determining PrPSc and neuropathological changes of inoculated animals.

Results: We report here the generation of the first CWD-derived infectious human PrPSc using elk CWD PrPSc to initiate conversion of human PrPC from normal human brain homogenates with PMCA in vitro. Western blotting with a human PrP selective antibody confirmed that the PMCA-generated protease-resistant PrPSc was derived from the human brain PrPC substrate. Two lines of humanized transgenic mice expressing human PrPC with either Val or Met at the polymorphic codon 129 developed clinical prion disease following intracerebral inoculation with the PMCA-generated CWD-derived human PrPSc. Diseased mice exhibited distinct PrPSc patterns and neuropathological changes in the brain.

Conclusions: Our study, using PMCA and animal bioassays, provides the first evidence that CWD PrPSc has the potential to overcome the species barrier and directly convert human PrPC into infectious PrPSc that can produce bona fide prion disease when inoculated into humanized transgenic mice.

Funded by: CJD Foundation and NIH

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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... 

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."


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 

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.

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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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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

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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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.

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9 Carrot plants as potential vectors for CWD transmission.

Paulina Soto1,2, Francisca Bravo-Risi1,2, Claudio Soto1, Rodrigo Morales1,2

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

***> We show that edible plant components can absorb prions from CWD-contaminated soils and transport them to their aerial parts.

***> Our results indicate that edible plants could participate as vectors of CWD transmission.

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

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

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

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

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

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

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

Samia Hannaouia, Irina Zemlyankinaa, Sheng Chun Changa, Maria Immaculata Arifina, Vincent Béringueb, Debbie McKenziec, Hermann M. Schatzla, and Sabine Gilcha 

 Results: Here, we provide the strongest evidence supporting the zoonotic potential of CWD prions, and their possible phenotype in humans. Inoculation of mice expressing human PrPCwith deer CWD isolates (strains Wisc-1 and 116AG) resulted in atypical clinical manifestations in > 75% of the mice, with myoclonus as leading clinical sign. Most of tg650brain homogenates were positive for seeding activity in RT-QuIC. Clinical disease and presentation was transmissible to 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. 


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

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

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

Published

22 August 2022


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

Samia Hannaoui1 · Irina Zemlyankina1 · Sheng Chun Chang1 · Maria Immaculata Arifn1 · Vincent Béringue2 · Debbie McKenzie3 · Hermann M. Schatzl1 · Sabine Gilch1

Received: 24 May 2022 / Revised: 5 August 2022 / Accepted: 7 August 2022

© The Author(s) 2022

Abstract

Prions cause infectious and fatal neurodegenerative diseases in mammals. Chronic wasting disease (CWD), a prion disease of cervids, spreads efficiently among wild and farmed animals. Potential transmission to humans of CWD is a growing concern due to its increasing prevalence. Here, we provide evidence for a zoonotic potential of CWD prions, and its probable signature using mice expressing human prion protein (PrP) as an infection model. Inoculation of these mice with deer CWD isolates resulted in atypical clinical manifestation with prion seeding activity and efficient transmissible infectivity in the brain and, remarkably, in feces, but without classical neuropathological or Western blot appearances of prion diseases. Intriguingly, the protease-resistant PrP in the brain resembled that found in a familial human prion disease and was transmissible upon second passage. Our results suggest that CWD might infect humans, although the transmission barrier is likely higher compared to zoonotic transmission of cattle prions. Notably, our data suggest a different clinical presentation, prion signature, and tissue tropism, which causes challenges for detection by current diagnostic assays. Furthermore, the presence of infectious prions in feces is concerning because if this occurs in humans, it is a source for human-to-human transmission. These findings have strong implications for public health and CWD management.

Keywords Chronic wasting disease · CWD · Zoonotic potential · Prion strains · Zoonotic prions

HIGHLIGHTS OF THIS STUDY

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

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

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

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

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

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

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

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Supplementary Information The online version contains supplementary material available at 


snip...see full text;


 
EFSA Panel on Biological Hazards (BIOHAZ) Antonia Ricci Ana Allende Declan Bolton Marianne Chemaly Robert Davies Pablo Salvador Fernández Escámez ... See all authors 

First published: 17 January 2018 https://doi.org/10.2903/j.efsa.2018.5132

also, see; 

8. Even though human TSE‐exposure risk through consumption of game from European cervids can be assumed to be minor, if at all existing, no final conclusion can be drawn due to the overall lack of scientific data. 

***> In particular the US data do not clearly exclude the possibility of human (sporadic or familial) TSE development due to consumption of venison. 

The Working Group thus recognizes a potential risk to consumers if a TSE would be present in European cervids. It might be prudent considering appropriate measures to reduce such a risk, e.g. excluding tissues such as CNS and lymphoid tissues from the human food chain, which would greatly reduce any potential risk for consumers.. However, it is stressed that currently, no data regarding a risk of TSE infections from cervid products are available. 


Research Paper

Cellular prion protein distribution in the vomeronasal organ, parotid, and scent glands of white-tailed deer and mule deer

Anthony Ness, Aradhana Jacob, Kelsey Saboraki, Alicia Otero, Danielle Gushue, Diana Martinez Moreno, Melanie de Peña, Xinli Tang, Judd Aiken, Susan Lingle & Debbie McKenzieORCID Icon show less

Pages 40-57 | Received 03 Feb 2022, Accepted 13 May 2022, Published online: 29 May 2022

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ABSTRACT

Chronic wasting disease (CWD) is a contagious and fatal transmissible spongiform encephalopathy affecting species of the cervidae family. CWD has an expanding geographic range and complex, poorly understood transmission mechanics. CWD is disproportionately prevalent in wild male mule deer and male white-tailed deer. Sex and species influences on CWD prevalence have been hypothesized to be related to animal behaviours that involve deer facial and body exocrine glands. Understanding CWD transmission potential requires a foundational knowledge of the cellular prion protein (PrPC) in glands associated with cervid behaviours. In this study, we characterized the presence and distribution of PrPC in six integumentary and two non-integumentary tissues of hunter-harvested mule deer (Odocoileus hemionus) and white-tailed deer (O. virginianus). We report that white-tailed deer expressed significantly more PrPC than their mule deer in the parotid, metatarsal, and interdigital glands. Females expressed more PrPC than males in the forehead and preorbital glands. The distribution of PrPC within the integumentary exocrine glands of the face and legs were localized to glandular cells, hair follicles, epidermis, and immune cell infiltrates. All tissues examined expressed sufficient quantities of PrPC to serve as possible sites of prion initial infection, propagation, and shedding.


ARS RESEARCH Generation of human chronic wasting disease in transgenic mice 

Publication Acceptance Date: 9/8/2021

Research Project: Pathobiology, Genetics, and Detection of Transmissible Spongiform Encephalopathies Location: Virus and Prion Research

Title: Generation of human chronic wasting disease in transgenic mice

Author item WANG, ZERUI - Case Western Reserve University (CWRU) item QIN, KEFENG - University Of Chicago item CAMACHO, MANUEL - Case Western Reserve University (CWRU) item SHEN, PINGPING - Case Western Reserve University (CWRU) item YUAN, JUE - Case Western Reserve University (CWRU) item Greenlee, Justin item CUI, LI - Jilin University item KONG, QINGZHONG - Case Western Reserve University (CWRU) item MASTRIANNI, JAMES - University Of Chicago item ZOU, WEN-QUAN - Case Western Reserve University (CWRU)

Submitted to: Acta Neuropathologica Publication Type: Peer Reviewed Journal Publication Acceptance Date: 9/8/2021 Publication Date: N/A Citation: N/A

Interpretive Summary: Prion diseases are invariably fatal neurologic diseases for which there is no known prevention or cure. Chronic wasting disease (CWD) is the prion disease of deer and elk and is present in farmed and free ranging herds throughout North America. To date there is no clear evidence that the CWD agent could be transmitted to humans. This manuscript describes the use of an in vitro technique, cell-free serial protein misfolding cyclic amplification (sPMCA), to generate a CWD prion that is infectious to transgenic mice expressing the human prion protein. This study provides the first evidence that CWD prions may be able to cause misfolding in the human prion protein. This information will impact medical experts and those involved in making policy for farmed cervids and wildlife.

Technical Abstract: Chronic wasting disease (CWD) is a cervid spongiform encephalopathy or prion disease caused by the infectious prion or PrPSc, a misfolded conformer of cellular prion protein (PrPC). It has rapidly spread in North America and also has been found in Asia and Europe. In contrast to the zoonotic mad cow disease that is the first animal prion disease found transmissible to humans, the transmissibility of CWD to humans remains uncertain although most previous studies have suggested that humans may not be susceptible to CWD. Here we report the generation of an infectious human PrPSc by seeding CWD PrPSc in normal human brain PrPC through the in vitro cell-free serial protein misfolding cyclic amplification (sPMCA). Western blotting confirms that the sPMCA-induced proteinase K-resistant PrPSc is a human form, evidenced by a PrP-specific antibody that recognizes human but not cervid PrP. Remarkably, two lines of humanized transgenic (Tg) mice expressing human PrP-129Val/Val (VV) or -129Met/Met (MM) polymorphism develop prion disease at 233 ± 6 (mean ± SE) days post-inoculation (dpi) and 552 ± 27 dpi, respectively, upon intracerebral inoculation with the sPMCA-generated PrPSc. The brain of diseased Tg mice reveals the electrophoretic profile of PrPSc similar to sporadic Creutzfeldt-Jakob disease (sCJD) MM1 or VV2 subtype but different neuropathological patterns. We believe that our study provides the first evidence that CWD PrPSc is able to convert human PrPC into PrPSc in vitro and the CWD-derived human PrPSc mimics atypical sCJD subtypes in humanized Tg mice.


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

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

Published: 26 September 2021

Generation of human chronic wasting disease in transgenic mice

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

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

Abstract

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

Snip...

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

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


i thought i might share some news about cwd zoonosis that i got, that i cannot share or post to the public yet, i promised for various reasons, one that it will cause a shit storm for sure, but it was something i really already knew from previous studies, but, i was told that ;

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''As you can imagine, 2 and 5 (especially 5) may raise alarms. The evidence we have for 4 are not as strong or tight as I would like to have. At this point, please do not post any of the points publicly yet, but you can refer to points 1-3 in private discussions and all 5 points when discussing with relevant public officials to highlight the long-term risks of CWD zoonosis.''

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

so, i figure your as about as official as it gets, and i think this science is extremely important for you to know and to converse about with your officials. it's about to burn a whole in my pocket. this is about as close as it will ever get for cwd zoonosis to be proven in my time, this and what Canada Czub et al found with the Macaques, plus an old study from cjd surveillance unit back that showed cjd and a 9% increase in risk from folks that eat venison, i will post all this below for your files Sir. i remember back in the BSE nvCJD days, from when the first BSE case in bovine was confirmed around 1984 maybe 83, i forget the good vets named that screwed it up first, Carol something, but from 83ish to 95 96 when nvCJD was linked to humans from BSE in cattle, so that took 10 to 15 years. hell, at that rate, especially with Texas and cwd zoonsis, hell, i'll be dead before it's official, if ever, so here ya go Sir. there was a grant study on cwd zoonosis that had been going on for some time, i followed it over the years, then the grant date for said study had expired, so, i thought i would write the good Professor about said study i.e. Professor Kong, CWRU et al. i will post the grant study abstract first, and then after that, what reply i got back, about said study that i was told not to post/publish...

CWD ZOONOSIS GRANT FIRST;

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Cervid to human prion transmission

Kong, Qingzhong 

Case Western Reserve University, Cleveland, OH, United States

 Abstract Prion disease is transmissible and invariably fatal. Chronic wasting disease (CWD) is the prion disease affecting deer, elk and moose, and it is a widespread and expanding epidemic affecting 22 US States and 2 Canadian provinces so far. CWD poses the most serious zoonotic prion transmission risks in North America because of huge venison consumption (>6 million deer/elk hunted and consumed annually in the USA alone), significant prion infectivity in muscles and other tissues/fluids from CWD-affected cervids, and usually high levels of individual exposure to CWD resulting from consumption of the affected animal among often just family and friends. However, we still do not know whether CWD prions can infect humans in the brain or peripheral tissues or whether clinical/asymptomatic CWD zoonosis has already occurred, and we have no essays to reliably detect CWD infection in humans. We hypothesize that: (1) The classic CWD prion strain can infect humans at low levels in the brain and peripheral lymphoid tissues; (2) The cervid-to-human transmission barrier is dependent on the cervid prion strain and influenced by the host (human) prion protein (PrP) primary sequence; (3) Reliable essays can be established to detect CWD infection in humans; and (4) CWD transmission to humans has already occurred. We will test these hypotheses in 4 Aims using transgenic (Tg) mouse models and complementary in vitro approaches. 

Aim 1 will prove that the classical CWD strain may infect humans in brain or peripheral lymphoid tissues at low levels by conducting systemic bioassays in a set of humanized Tg mouse lines expressing common human PrP variants using a number of CWD isolates at varying doses and routes. Experimental human CWD samples will also be generated for Aim 3. 

Aim 2 will test the hypothesis that the cervid-to-human prion transmission barrier is dependent on prion strain and influenced by the host (human) PrP sequence by examining and comparing the transmission efficiency and phenotypes of several atypical/unusual CWD isolates/strains as well as a few prion strains from other species that have adapted to cervid PrP sequence, utilizing the same panel of humanized Tg mouse lines as in Aim 1. 

Aim 3 will establish reliable essays for detection and surveillance of CWD infection in humans by examining in details the clinical, pathological, biochemical and in vitro seeding properties of existing and future experimental human CWD samples generated from Aims 1-2 and compare them with those of common sporadic human Creutzfeldt-Jakob disease (sCJD) prions. 

Aim 4 will attempt to detect clinical CWD-affected human cases by examining a significant number of brain samples from prion-affected human subjects in the USA and Canada who have consumed venison from CWD-endemic areas utilizing the criteria and essays established in Aim 3. The findings from this proposal will greatly advance our understandings on the potential and characteristics of cervid prion transmission in humans, establish reliable essays for CWD zoonosis and potentially discover the first case(s) of CWD infection in humans.

Public Health Relevance There are significant and increasing human exposure to cervid prions because chronic wasting disease (CWD, a widespread and highly infectious prion disease among deer and elk in North America) continues spreading and consumption of venison remains popular, but our understanding on cervid-to-human prion transmission is still very limited, raising public health concerns. This proposal aims to define the zoonotic risks of cervid prions and set up and apply essays to detect CWD zoonosis using mouse models and in vitro methods. The findings will greatly expand our knowledge on the potentials and characteristics of cervid prion transmission in humans, establish reliable essays for such infections and may discover the first case(s) of CWD infection in humans.

 Funding Agency Agency National Institute of Health (NIH) Institute National Institute of Neurological Disorders and Stroke (NINDS) Type Research Project (R01) Project # 1R01NS088604-01A1 Application # 9037884 Study Section Cellular and Molecular Biology of Neurodegeneration Study Section (CMND) Program Officer Wong, May Project Start 2015-09-30 Project End 2019-07-31 Budget Start 2015-09-30 Budget End 2016-07-31 Support Year 1 Fiscal Year 2015 Total Cost $337,507 Indirect Cost $118,756

snip... 


Professor Kongs reply to me just this month about above grant study that has NOT been published in peer reveiw yet...

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Here is a brief summary of our findings:

snip...can't post, made a promise...tss

On Sat, Apr 3, 2021 at 12:19 PM Terry Singeltary <flounder9@verizon.net> wrote:

snip...

end...tss

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CWD ZOONOSIS THE FULL MONTY TO DATE

International Conference on Emerging Diseases, Outbreaks & Case Studies & 16th Annual Meeting on Influenza March 28-29, 2018 | Orlando, USA

Qingzhong Kong

Case Western Reserve University School of Medicine, USA

Zoonotic potential of chronic wasting disease prions from cervids

Chronic wasting disease (CWD) is the prion disease in cervids (mule deer, white-tailed deer, American elk, moose, and reindeer). It has become an epidemic in North America, and it has been detected in the Europe (Norway) since 2016. The widespread CWD and popular hunting and consumption of cervid meat and other products raise serious public health concerns, but questions remain on human susceptibility to CWD prions, especially on the potential difference in zoonotic potential among the various CWD prion strains. We have been working to address this critical question for well over a decade. We used CWD samples from various cervid species to inoculate transgenic mice expressing human or elk prion protein (PrP). We found infectious prions in the spleen or brain in a small fraction of CWD-inoculated transgenic mice expressing human PrP, indicating that humans are not completely resistant to CWD prions; this finding has significant ramifications on the public health impact of CWD prions. The influence of cervid PrP polymorphisms, the prion strain dependence of CWD-to-human transmission barrier, and the characterization of experimental human CWD prions will be discussed.

Speaker Biography Qingzhong Kong has completed his PhD from the University of Massachusetts at Amherst and Post-doctoral studies at Yale University. He is currently an Associate Professor of Pathology, Neurology and Regenerative Medicine. He has published over 50 original research papers in reputable journals (including Science Translational Medicine, JCI, PNAS and Cell Reports) and has been serving as an Editorial Board Member on seven scientific journals. He has multiple research interests, including public health risks of animal prions (CWD of cervids and atypical BSE of cattle), animal modeling of human prion diseases, mechanisms of prion replication and pathogenesis, etiology of sporadic Creutzfeldt-Jacob disease (CJD) in humans, normal cellular PrP in the biology and pathology of multiple brain and peripheral diseases, proteins responsible for the α-cleavage of cellular PrP, as well as gene therapy and DNA vaccination.

qxk2@case.edu 




SUNDAY, JULY 25, 2021 

North American and Norwegian Chronic Wasting Disease prions exhibit different potential for interspecies transmission and zoonotic risk 

''Our data suggest that reindeer and red deer from Norway could be the most transmissible CWD prions to other mammals, whereas North American CWD prions were more prone to generate human prions in vitro.''


MONDAY, JULY 19, 2021 

***> U Calgary researchers at work on a vaccine against a fatal infectious disease affecting deer and potentially people


Prion Conference 2018 Abstracts

BSE aka MAD COW DISEASE, was first discovered in 1984, and it took until 1995 to finally admit that BSE was causing nvCJD, the rest there is history, but that science is still evolving i.e. science now shows that indeed atypical L-type BSE, atypical Nor-98 Scrapie, and typical Scrapie are all zoonosis, zoonotic for humans, there from. 

HOW long are we going to wait for Chronic Wasting Disease, CWD TSE Prion of Cervid, and zoonosis, zoonotic tranmission to humans there from?

Studies have shown since 1994 that humans are susceptible to CWD TSE Prion, so, what's the hold up with making CWD a zoonotic zoonosis disease, the iatrogenic transmissions there from is not waiting for someone to make a decision.

Prion Conference 2018 Abstracts

P190 Human prion disease mortality rates by occurrence of chronic wasting disease in freeranging cervids, United States

Abrams JY (1), Maddox RA (1), Schonberger LB (1), Person MK (1), Appleby BS (2), Belay ED (1)

(1) Centers for Disease Control and Prevention (CDC), National Center for Emerging and Zoonotic Infectious Diseases, Atlanta, GA, USA (2) Case Western Reserve University, National Prion Disease Pathology Surveillance Center (NPDPSC), Cleveland, OH, USA.

Background

Chronic wasting disease (CWD) is a prion disease of deer and elk that has been identified in freeranging cervids in 23 US states. While there is currently no epidemiological evidence for zoonotic transmission through the consumption of contaminated venison, studies suggest the CWD agent can cross the species barrier in experimental models designed to closely mimic humans. We compared rates of human prion disease in states with and without CWD to examine the possibility of undetermined zoonotic transmission.

Methods

Death records from the National Center for Health Statistics, case records from the National Prion Disease Pathology Surveillance Center, and additional state case reports were combined to create a database of human prion disease cases from 2003-2015. Identification of CWD in each state was determined through reports of positive CWD tests by state wildlife agencies. Age- and race-adjusted mortality rates for human prion disease, excluding cases with known etiology, were determined for four categories of states based on CWD occurrence: highly endemic (>16 counties with CWD identified in free-ranging cervids); moderately endemic (3-10 counties with CWD); low endemic (1-2 counties with CWD); and no CWD states. States were counted as having no CWD until the year CWD was first identified. Analyses stratified by age, sex, and time period were also conducted to focus on subgroups for which zoonotic transmission would be more likely to be detected: cases <55 years old, male sex, and the latter half of the study (2010-2015).

Results

Highly endemic states had a higher rate of prion disease mortality compared to non-CWD states (rate ratio [RR]: 1.12, 95% confidence interval [CI] = 1.01 - 1.23), as did low endemic states (RR: 1.15, 95% CI = 1.04 - 1.27). Moderately endemic states did not have an elevated mortality rate (RR: 1.05, 95% CI = 0.93 - 1.17). In age-stratified analyses, prion disease mortality rates among the <55 year old population were elevated for moderately endemic states (RR: 1.57, 95% CI = 1.10 – 2.24) while mortality rates were elevated among those ≥55 for highly endemic states (RR: 1.13, 95% CI = 1.02 - 1.26) and low endemic states (RR: 1.16, 95% CI = 1.04 - 1.29). In other stratified analyses, prion disease mortality rates for males were only elevated for low endemic states (RR: 1.27, 95% CI = 1.10 - 1.48), and none of the categories of CWD-endemic states had elevated mortality rates for the latter time period (2010-2015).

Conclusions

While higher prion disease mortality rates in certain categories of states with CWD in free-ranging cervids were noted, additional stratified analyses did not reveal markedly elevated rates for potentially sensitive subgroups that would be suggestive of zoonotic transmission. Unknown confounding factors or other biases may explain state-by-state differences in prion disease mortality.

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P172 Peripheral Neuropathy in Patients with Prion Disease

Wang H(1), Cohen M(1), Appleby BS(1,2)

(1) University Hospitals Cleveland Medical Center, Cleveland, Ohio (2) National Prion Disease Pathology Surveillance Center, Cleveland, Ohio.

Prion disease is a fatal progressive neurodegenerative disease due to deposition of an abnormal protease-resistant isoform of prion protein. Typical symptoms include rapidly progressive dementia, myoclonus, visual disturbance and hallucinations. Interestingly, in patients with prion disease, the abnormal protein canould also be found in the peripheral nervous system. Case reports of prion deposition in peripheral nerves have been reported. Peripheral nerve involvement is thought to be uncommon; however, little is known about the exact prevalence and features of peripheral neuropathy in patients with prion disease.

We reviewed autopsy-proven prion cases from the National Prion Disease Pathology Surveillance Center that were diagnosed between September 2016 to March 2017. We collected information regarding prion protein diagnosis, demographics, comorbidities, clinical symptoms, physical exam, neuropathology, molecular subtype, genetics lab, brain MRI, image and EMG reports. Our study included 104 patients. Thirteen (12.5%) patients had either subjective symptoms or objective signs of peripheral neuropathy. Among these 13 patients, 3 had other known potential etiologies of peripheral neuropathy such as vitamin B12 deficiency or prior chemotherapy. Among 10 patients that had no other clear etiology, 3 (30%) had familial CJD. The most common sCJD subtype was MV1-2 (30%), followed by MM1-2 (20%). The Majority of cases wasere male (60%). Half of them had exposure to wild game. The most common subjective symptoms were tingling and/or numbness of distal extremities. The most common objective finding was diminished vibratory sensation in the feet. Half of them had an EMG with the findings ranging from fasciculations to axonal polyneuropathy or demyelinating polyneuropathy.

Our study provides an overview of the pattern of peripheral neuropathy in patients with prion disease. Among patients with peripheral neuropathy symptoms or signs, majority has polyneuropathy. It is important to document the baseline frequency of peripheral neuropathy in prion diseases as these symptoms may become important when conducting surveillance for potential novel zoonotic prion diseases.

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P177 PrP plaques in methionine homozygous Creutzfeldt-Jakob disease patients as a potential marker of iatrogenic transmission

Abrams JY (1), Schonberger LB (1), Cali I (2), Cohen Y (2), Blevins JE (2), Maddox RA (1), Belay ED (1), Appleby BS (2), Cohen ML (2)

(1) Centers for Disease Control and Prevention (CDC), National Center for Emerging and Zoonotic Infectious Diseases, Atlanta, GA, USA (2) Case Western Reserve University, National Prion Disease Pathology Surveillance Center (NPDPSC), Cleveland, OH, USA.

Background

Sporadic Creutzfeldt-Jakob disease (CJD) is widely believed to originate from de novo spontaneous conversion of normal prion protein (PrP) to its pathogenic form, but concern remains that some reported sporadic CJD cases may actually be caused by disease transmission via iatrogenic processes. For cases with methionine homozygosity (CJD-MM) at codon 129 of the PRNP gene, recent research has pointed to plaque-like PrP deposition as a potential marker of iatrogenic transmission for a subset of cases. This phenotype is theorized to originate from specific iatrogenic source CJD types that comprise roughly a quarter of known CJD cases.

Methods

We reviewed scientific literature for studies which described PrP plaques among CJD patients with known epidemiological links to iatrogenic transmission (receipt of cadaveric human grown hormone or dura mater), as well as in cases of reported sporadic CJD. The presence and description of plaques, along with CJD classification type and other contextual factors, were used to summarize the current evidence regarding plaques as a potential marker of iatrogenic transmission. In addition, 523 cases of reported sporadic CJD cases in the US from January 2013 through September 2017 were assessed for presence of PrP plaques.

Results

We identified four studies describing 52 total cases of CJD-MM among either dura mater recipients or growth hormone recipients, of which 30 were identified as having PrP plaques. While sporadic cases were not generally described as having plaques, we did identify case reports which described plaques among sporadic MM2 cases as well as case reports of plaques exclusively in white matter among sporadic MM1 cases. Among the 523 reported sporadic CJD cases, 0 of 366 MM1 cases had plaques, 2 of 48 MM2 cases had kuru plaques, and 4 of 109 MM1+2 cases had either kuru plaques or both kuru and florid plaques. Medical chart review of the six reported sporadic CJD cases with plaques did not reveal clinical histories suggestive of potential iatrogenic transmission.

Conclusions

PrP plaques occur much more frequently for iatrogenic CJD-MM cases compared to sporadic CJDMM cases. Plaques may indicate iatrogenic transmission for CJD-MM cases without a type 2 Western blot fragment. The study results suggest the absence of significant misclassifications of iatrogenic CJD as sporadic. To our knowledge, this study is the first to describe grey matter kuru plaques in apparently sporadic CJD-MM patients with a type 2 Western blot fragment.

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P180 Clinico-pathological analysis of human prion diseases in a brain bank series

Ximelis T (1), Aldecoa I (1,2), Molina-Porcel L (1,3), Grau-Rivera O (4), Ferrer I (5), Nos C (6), Gelpi E (1,7), Sánchez-Valle R (1,4)

(1) Neurological Tissue Bank of the Biobanc-Hospital ClÃnic-IDIBAPS, Barcelona, Spain (2) Pathological Service of Hospital ClÃnic de Barcelona, Barcelona, Spain (3) EAIA Trastorns Cognitius, Centre Emili Mira, Parc de Salut Mar, Barcelona, Spain (4) Department of Neurology of Hospital ClÃnic de Barcelona, Barcelona, Spain (5) Institute of Neuropathology, Hospital Universitari de Bellvitge, Hospitalet de Llobregat, Barcelona (6) General subdirectorate of Surveillance and Response to Emergencies in Public Health, Department of Public Health in Catalonia, Barcelona, Spain (7) Institute of Neurology, Medical University of Vienna, Vienna, Austria.

Background and objective:

The Neurological Tissue Bank (NTB) of the Hospital Clínic-Institut d‘Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain is the reference center in Catalonia for the neuropathological study of prion diseases in the region since 2001. The aim of this study is to analyse the characteristics of the confirmed prion diseases registered at the NTB during the last 15 years.

Methods:

We reviewed retrospectively all neuropathologically confirmed cases registered during the period January 2001 to December 2016.

Results:

176 cases (54,3% female, mean age: 67,5 years and age range: 25-86 years) of neuropathological confirmed prion diseases have been studied at the NTB. 152 cases corresponded to sporadic Creutzfeldt-Jakob disease (sCJD), 10 to genetic CJD, 10 to Fatal Familial Insomnia, 2 to GerstmannSträussler-Scheinker disease, and 2 cases to variably protease-sensitive prionopathy (VPSPr). Within sCJD subtypes the MM1 subtype was the most frequent, followed by the VV2 histotype.

Clinical and neuropathological diagnoses agreed in 166 cases (94%). The clinical diagnosis was not accurate in 10 patients with definite prion disease: 1 had a clinical diagnosis of Fronto-temporal dementia (FTD), 1 Niemann-Pick‘s disease, 1 Lewy Body‘s Disease, 2 Alzheimer‘s disease, 1 Cortico-basal syndrome and 2 undetermined dementia. Among patients with VPSPr, 1 had a clinical diagnosis of Amyotrophic lateral sclerosis (ALS) and the other one with FTD.

Concomitant pathologies are frequent in older age groups, mainly AD neuropathological changes were observed in these subjects.

Discussion:

A wide spectrum of human prion diseases have been identified in the NTB being the relative frequencies and main characteristics like other published series. There is a high rate of agreement between clinical and neuropathological diagnoses with prion diseases. These findings show the importance that public health has given to prion diseases during the past 15 years. Continuous surveillance of human prion disease allows identification of new emerging phenotypes. Brain tissue samples from these donors are available to the scientific community. For more information please visit:


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P192 Prion amplification techniques for the rapid evaluation of surface decontamination procedures

Bruyere-Ostells L (1), Mayran C (1), Belondrade M (1), Boublik Y (2), Haïk S (3), Fournier-Wirth C (1), Nicot S (1), Bougard D (1)

(1) Pathogenesis and control of chronic infections, Etablissement Français du Sang, Inserm, Université de Montpellier, Montpellier, France. (2) Centre de Recherche en Biologie cellulaire de Montpellier, CNRS, Université de Montpellier, Montpellier, France. (3) Inserm U 1127, CNRS UMR 7225, Sorbonne Universités, UPMC Université Paris 06 UMR S 1127, Institut du Cerveau et de la Moelle épinière, ICM, Paris, France.

Aims:

Transmissible Spongiform Encephalopathies (TSE) or prion diseases are a group of incurable and always fatal neurodegenerative disorders including Creutzfeldt-Jakob diseases (CJD) in humans. These pathologies include sporadic (sCJD), genetic and acquired (variant CJD) forms. By the past, sCJD and vCJD were transmitted by different prion contaminated biological materials to patients resulting in more than 400 iatrogenic cases (iCJD). The atypical nature and the biochemical properties of the infectious agent, formed by abnormal prion protein or PrPTSE, make it particularly resistant to conventional decontamination procedures. In addition, PrPTSE is widely distributed throughout the organism before clinical onset in vCJD and can also be detected in some peripheral tissues in sporadic CJD. Risk of iatrogenic transmission of CJD by contaminated medical device remains thus a concern for healthcare facilities. Bioassay is the gold standard method to evaluate the efficacy of prion decontamination procedures but is time-consuming and expensive. Here, we propose to compare in vitro prion amplification techniques: Protein Misfolding Cyclic Amplification (PMCA) and Real-Time Quaking Induced Conversion (RT-QuIC) for the detection of residual prions on surface after decontamination.

Methods:

Stainless steel wires, by mimicking the surface of surgical instruments, were proposed as a carrier model of prions for inactivation studies. To determine the sensitivity of the two amplification techniques on wires (Surf-PMCA and Surf-QuIC), steel wires were therefore contaminated with serial dilutions of brain homogenates (BH) from a 263k infected hamster and from a patient with sCJD (MM1 subtype). We then compared the different standard decontamination procedures including partially and fully efficient treatments by detecting the residual seeding activity on 263K and sCJD contaminated wires. We completed our study by the evaluation of marketed reagents endorsed for prion decontamination.

Results:

The two amplification techniques can detect minute quantities of PrPTSE adsorbed onto a single wire. 8/8 wires contaminated with a 10-6 dilution of 263k BH and 1/6 with the 10-8 dilution are positive with Surf-PMCA. Similar performances were obtained with Surf-QuIC on 263K: 10/16 wires contaminated with 10-6 dilution and 1/8 wires contaminated with 10-8 dilution are positive. Regarding the human sCJD-MM1 prion, Surf-QuIC allows us to detect 16/16 wires contaminated with 10-6 dilutions and 14/16 with 10-7 . Results obtained after decontamination treatments are very similar between 263K and sCJD prions. Efficiency of marketed treatments to remove prions is lower than expected.

Conclusions:

Surf-PMCA and Surf-QuIC are very sensitive methods for the detection of prions on wires and could be applied to prion decontamination studies for rapid evaluation of new treatments. Sodium hypochlorite is the only product to efficiently remove seeding activity of both 263K and sCJD prions.

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WA2 Oral transmission of CWD into Cynomolgus macaques: signs of atypical disease, prion conversion and infectivity in macaques and bio-assayed transgenic mice

Schatzl HM (1, 2), Hannaoui S (1, 2), Cheng Y-C (1, 2), Gilch S (1, 2), Beekes M (3), SchulzSchaeffer W (4), Stahl-Hennig C (5) and Czub S (2, 6)

(1) University of Calgary, Calgary Prion Research Unit, Calgary, Canada (2) University of Calgary, Faculty of Veterinary Medicine, Calgary, Canada, (3) Robert Koch Institute, Berlin, Germany, (4) University of Homburg/Saar, Homburg, Germany, (5) German Primate Center, Goettingen, Germany, (6) Canadian Food Inspection Agency (CFIA), Lethbridge, Canada.

To date, BSE is the only example of interspecies transmission of an animal prion disease into humans. The potential zoonotic transmission of CWD is an alarming issue and was addressed by many groups using a variety of in vitro and in vivo experimental systems. Evidence from these studies indicated a substantial, if not absolute, species barrier, aligning with the absence of epidemiological evidence suggesting transmission into humans. Studies in non-human primates were not conclusive so far, with oral transmission into new-world monkeys and no transmission into old-world monkeys. Our consortium has challenged 18 Cynomolgus macaques with characterized CWD material, focusing on oral transmission with muscle tissue. Some macaques have orally received a total of 5 kg of muscle material over a period of 2 years. After 5-7 years of incubation time some animals showed clinical symptoms indicative of prion disease, and prion neuropathology and PrPSc deposition were found in spinal cord and brain of euthanized animals. PrPSc in immunoblot was weakly detected in some spinal cord materials and various tissues tested positive in RT-QuIC, including lymph node and spleen homogenates. To prove prion infectivity in the macaque tissues, we have intracerebrally inoculated 2 lines of transgenic mice, expressing either elk or human PrP. At least 3 TgElk mice, receiving tissues from 2 different macaques, showed clinical signs of a progressive prion disease and brains were positive in immunoblot and RT-QuIC. Tissues (brain, spinal cord and spleen) from these and preclinical mice are currently tested using various read-outs and by second passage in mice. Transgenic mice expressing human PrP were so far negative for clear clinical prion disease (some mice >300 days p.i.). In parallel, the same macaque materials are inoculated into bank voles. Taken together, there is strong evidence of transmissibility of CWD orally into macaques and from macaque tissues into transgenic mouse models, although with an incomplete attack rate. The clinical and pathological presentation in macaques was mostly atypical, with a strong emphasis on spinal cord pathology. Our ongoing studies will show whether the transmission of CWD into macaques and passage in transgenic mice represents a form of non-adaptive prion amplification, and whether macaque-adapted prions have the potential to infect mice expressing human PrP. The notion that CWD can be transmitted orally into both new-world and old-world non-human primates asks for a careful reevaluation of the zoonotic risk of CWD.

See also poster P103

***> The notion that CWD can be transmitted orally into both new-world and old-world non-human primates asks for a careful reevaluation of the zoonotic risk of CWD.

=====

WA16 Monitoring Potential CWD Transmission to Humans

Belay ED

Centers for Disease Control and Prevention (CDC), National Center for Emerging and Zoonotic Infectious Diseases, Atlanta, GA, USA.

The spread of chronic wasting disease (CWD) in animals has raised concerns about increasing human exposure to the CWD agent via hunting and venison consumption, potentially facilitating CWD transmission to humans. Several studies have explored this possibility, including limited epidemiologic studies, in vitro experiments, and laboratory studies using various types of animal models. Most human exposures to the CWD agent in the United States would be expected to occur in association with deer and elk hunting in CWD-endemic areas. The Centers for Disease Control and Prevention (CDC) collaborated with state health departments in Colorado, Wisconsin, and Wyoming to identify persons at risk of CWD exposure and to monitor their vital status over time. Databases were established of persons who hunted in Colorado and Wyoming and those who reported consumption of venison from deer that later tested positive in Wisconsin. Information from the databases is periodically cross-checked with mortality data to determine the vital status and causes of death for deceased persons. Long-term follow-up of these hunters is needed to assess their risk of development of a prion disease linked to CWD exposure.

=====

P166 Characterization of CJD strain profiles in venison consumers and non-consumers from Alberta and Saskatchewan

Stephanie Booth (1,2), Lise Lamoureux (1), Debra Sorensen (1), Jennifer L. Myskiw (1,2), Megan Klassen (1,2), Michael Coulthart (3), Valerie Sim (4)

(1) Zoonotic Diseases and Special Pathogens, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg (2) Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg (3) Canadian CJD Surveillance System, Public Health Agency of Canada, Ottawa (4) Division of Neurology, Department of Medicine Centre for Prions and Protein Folding Diseases, University of Alberta, Edmonton.

Chronic wasting disease (CWD) is spreading rapidly through wild cervid populations in the Canadian provinces of Alberta and Saskatchewan. While this has implications for tourism and hunting, there is also concern over possible zoonotic transmission to humans who eat venison from infected deer. Whilst there is no evidence of any human cases of CWD to date, the Canadian CJD Surveillance System (CJDSS) in Canada is staying vigilant. When variant CJD occurred following exposure to BSE, the unique biochemical fingerprint of the pathologic PrP enabled a causal link to be confirmed. However, we cannot be sure what phenotype human CWD prions would present with, or indeed, whether this would be distinct from that see in sporadic CJD. Therefore we are undertaking a systematic analysis of the molecular diversity of CJD cases of individuals who resided in Alberta and Saskatchewan at their time of death comparing venison consumers and non-consumers, using a variety of clinical, imaging, pathological and biochemical markers. Our initial objective is to develop novel biochemical methodologies that will extend the baseline glycoform and genetic polymorphism typing that is already completed by the CJDSS. Firstly, we are reviewing MRI, EEG and pathology information from over 40 cases of CJD to select clinically affected areas for further investigation. Biochemical analysis will include assessment of the levels of protease sensitive and resistant prion protein, glycoform typing using 2D gel electrophoresis, testing seeding capabilities and kinetics of aggregation by quaking-induced conversion, and determining prion oligomer size distributions with asymmetric flow field fractionation with in-line light scattering. Progress and preliminary data will be presented. Ultimately, we intend to further define the relationship between PrP structure and disease phenotype and establish a baseline for the identification of future atypical CJD cases that may arise as a result of exposure to CWD.

=====

Source Prion Conference 2018 Abstracts




Volume 24, Number 8—August 2018 
Research Susceptibility of Human Prion Protein to Conversion by Chronic Wasting Disease Prions
Marcelo A. BarriaComments to Author , Adriana Libori, Gordon Mitchell, and Mark W. Head Author affiliations: National CJD Research and Surveillance Unit, University of Edinburgh, Edinburgh, Scotland, UK (M.A. Barria, A. Libori, M.W. Head); National and OIE Reference Laboratory for Scrapie and CWD, Canadian Food Inspection Agency, Ottawa, Ontario, Canada (G. Mitchell)

Abstract Chronic wasting disease (CWD) is a contagious and fatal neurodegenerative disease and a serious animal health issue for deer and elk in North America. The identification of the first cases of CWD among free-ranging reindeer and moose in Europe brings back into focus the unresolved issue of whether CWD can be zoonotic like bovine spongiform encephalopathy. We used a cell-free seeded protein misfolding assay to determine whether CWD prions from elk, white-tailed deer, and reindeer in North America can convert the human prion protein to the disease-associated form. We found that prions can convert, but the efficiency of conversion is affected by polymorphic variation in the cervid and human prion protein genes. In view of the similarity of reindeer, elk, and white-tailed deer in North America to reindeer, red deer, and roe deer, respectively, in Europe, a more comprehensive and thorough assessment of the zoonotic potential of CWD might be warranted.

snip...

Discussion Characterization of the transmission properties of CWD and evaluation of their zoonotic potential are important for public health purposes. Given that CWD affects several members of the family Cervidae, it seems reasonable to consider whether the zoonotic potential of CWD prions could be affected by factors such as CWD strain, cervid species, geographic location, and Prnp–PRNP polymorphic variation. We have previously used an in vitro conversion assay (PMCA) to investigate the susceptibility of the human PrP to conversion to its disease-associated form by several animal prion diseases, including CWD (15,16,22). The sensitivity of our molecular model for the detection of zoonotic conversion depends on the combination of 1) the action of proteinase K to degrade the abundant human PrPC that constitutes the substrate while only N terminally truncating any human PrPres produced and 2) the presence of the 3F4 epitope on human but not cervid PrP. In effect, this degree of sensitivity means that any human PrPres formed during the PMCA reaction can be detected down to the limit of Western blot sensitivity. In contrast, if other antibodies that detect both cervid and human PrP are used, such as 6H4, then newly formed human PrPres must be detected as a measurable increase in PrPres over the amount remaining in the reaction product from the cervid seed. Although best known for the efficient amplification of prions in research and diagnostic contexts, the variation of the PMCA method employed in our study is optimized for the definitive detection of zoonotic reaction products of inherently inefficient conversion reactions conducted across species barriers. By using this system, we previously made and reported the novel observation that elk CWD prions could convert human PrPC from human brain and could also convert recombinant human PrPC expressed in transgenic mice and eukaryotic cell cultures (15).

A previous publication suggested that mule deer PrPSc was unable to convert humanized transgenic substrate in PMCA assays (23) and required a further step of in vitro conditioning in deer substrate PMCA before it was able to cross the deer–human molecular barrier (24). However, prions from other species, such as elk (15) and reindeer affected by CWD, appear to be compatible with the human protein in a single round of amplification (as shown in our study). These observations suggest that different deer species affected by CWD could present differing degrees of the olecular compatibility with the normal form of human PrP.

The contribution of the polymorphism at codon 129 of the human PrP gene has been extensively studied and is recognized as a risk factor for Creutzfeldt-Jakob disease (4). In cervids, the equivalent codon corresponds to the position 132 encoding methionine or leucine. This polymorphism in the elk gene has been shown to play an important role in CWD susceptibility (25,26). We have investigated the effect of this cervid Prnp polymorphism on the conversion of the humanized transgenic substrate according to the variation in the equivalent PRNP codon 129 polymorphism. Interestingly, only the homologs methionine homozygous seed–substrate reactions could readily convert the human PrP, whereas the heterozygous elk PrPSc was unable to do so, even though comparable amounts of PrPres were used to seed the reaction. In addition, we observed only low levels of human PrPres formation in the reactions seeded with the homozygous methionine (132 MM) and the heterozygous (132 ML) seeds incubated with the other 2 human polymorphic substrates (129 MV and 129 VV). The presence of the amino acid leucine at position 132 of the elk Prnp gene has been attributed to a lower degree of prion conversion compared with methionine on the basis of experiments in mice made transgenic for these polymorphic variants (26). Considering the differences observed for the amplification of the homozygous human methionine substrate by the 2 polymorphic elk seeds (MM and ML), reappraisal of the susceptibility of human PrPC by the full range of cervid polymorphic variants affected by CWD would be warranted.

In light of the recent identification of the first cases of CWD in Europe in a free-ranging reindeer (R. tarandus) in Norway (2), we also decided to evaluate the in vitro conversion potential of CWD in 2 experimentally infected reindeer (18). Formation of human PrPres was readily detectable after a single round of PMCA, and in all 3 humanized polymorphic substrates (MM, MV, and VV). This finding suggests that CWD prions from reindeer could be more compatible with human PrPC generally and might therefore present a greater risk for zoonosis than, for example, CWD prions from white-tailed deer. A more comprehensive comparison of CWD in the affected species, coupled with the polymorphic variations in the human and deer PRNP–Prnp genes, in vivo and in vitro, will be required before firm conclusions can be drawn. Analysis of the Prnp sequence of the CWD reindeer in Norway was reported to be identical to the specimens used in our study (2). This finding raises the possibility of a direct comparison of zoonotic potential between CWD acquired in the wild and that produced in a controlled laboratory setting. (Table).

The prion hypothesis proposes that direct molecular interaction between PrPSc and PrPC is necessary for conversion and prion replication. Accordingly, polymorphic variants of the PrP of host and agent might play a role in determining compatibility and potential zoonotic risk. In this study, we have examined the capacity of the human PrPC to support in vitro conversion by elk, white-tailed deer, and reindeer CWD PrPSc. Our data confirm that elk CWD prions can convert the human PrPC, at least in vitro, and show that the homologous PRNP polymorphisms at codon 129 and 132 in humans and cervids affect conversion efficiency. Other species affected by CWD, particularly caribou or reindeer, also seem able to convert the human PrP. It will be important to determine whether other polymorphic variants found in other CWD-affected Cervidae or perhaps other factors (17) exert similar effects on the ability to convert human PrP and thus affect their zoonotic potential.

Dr. Barria is a research scientist working at the National CJD Research and Surveillance Unit, University of Edinburgh. His research has focused on understanding the molecular basis of a group of fatal neurologic disorders called prion diseases.

Acknowledgments We thank Aru Balachandran for originally providing cervid brain tissues, Abigail Diack and Jean Manson for providing mouse brain tissue, and James Ironside for his critical reading of the manuscript at an early stage.

This report is independent research commissioned and funded by the United Kingdom’s Department of Health Policy Research Programme and the Government of Scotland. The views expressed in this publication are those of the authors and not necessarily those of the Department of Health or the Government of Scotland.

Author contributions: The study was conceived and designed by M.A.B. and M.W.H. The experiments were conducted by M.A.B. and A.L. Chronic wasting disease brain specimens were provided by G.M. The manuscript was written by M.A.B. and M.W.H. All authors contributed to the editing and revision of the manuscript.


Prion 2017 Conference Abstracts
First evidence of intracranial and peroral transmission of Chronic Wasting Disease (CWD) into Cynomolgus macaques: a work in progress Stefanie Czub1, Walter Schulz-Schaeffer2, Christiane Stahl-Hennig3, Michael Beekes4, Hermann Schaetzl5 and Dirk Motzkus6 1 
University of Calgary Faculty of Veterinary Medicine/Canadian Food Inspection Agency; 2Universitatsklinikum des Saarlandes und Medizinische Fakultat der Universitat des Saarlandes; 3 Deutsches Primaten Zentrum/Goettingen; 4 Robert-Koch-Institut Berlin; 5 University of Calgary Faculty of Veterinary Medicine; 6 presently: Boehringer Ingelheim Veterinary Research Center; previously: Deutsches Primaten Zentrum/Goettingen 
This is a progress report of a project which started in 2009. 
21 cynomolgus macaques were challenged with characterized CWD material from white-tailed deer (WTD) or elk by intracerebral (ic), oral, and skin exposure routes. Additional blood transfusion experiments are supposed to assess the CWD contamination risk of human blood product. Challenge materials originated from symptomatic cervids for ic, skin scarification and partially per oral routes (WTD brain). Challenge material for feeding of muscle derived from preclinical WTD and from preclinical macaques for blood transfusion experiments. We have confirmed that the CWD challenge material contained at least two different CWD agents (brain material) as well as CWD prions in muscle-associated nerves. 
Here we present first data on a group of animals either challenged ic with steel wires or per orally and sacrificed with incubation times ranging from 4.5 to 6.9 years at postmortem. Three animals displayed signs of mild clinical disease, including anxiety, apathy, ataxia and/or tremor. In four animals wasting was observed, two of those had confirmed diabetes. 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. Protein misfolding cyclic amplification (PMCA), real-time quaking-induced conversion (RT-QuiC) and PET-blot assays to further substantiate these findings are on the way, as well as bioassays in bank voles and transgenic mice. 
At present, a total of 10 animals are sacrificed and read-outs are ongoing. Preclinical incubation of the remaining macaques covers a range from 6.4 to 7.10 years. Based on the species barrier and an incubation time of > 5 years for BSE in macaques and about 10 years for scrapie in macaques, we expected an onset of clinical disease beyond 6 years post inoculation. 
PRION 2017 DECIPHERING NEURODEGENERATIVE DISORDERS ABSTRACTS REFERENCE
8. Even though human TSE‐exposure risk through consumption of game from European cervids can be assumed to be minor, if at all existing, no final conclusion can be drawn due to the overall lack of scientific data. In particular the US data do not clearly exclude the possibility of human (sporadic or familial) TSE development due to consumption of venison. The Working Group thus recognizes a potential risk to consumers if a TSE would be present in European cervids. It might be prudent considering appropriate measures to reduce such a risk, e.g. excluding tissues such as CNS and lymphoid tissues from the human food chain, which would greatly reduce any potential risk for consumers. However, it is stressed that currently, no data regarding a risk of TSE infections from cervid products are available.  


SATURDAY, FEBRUARY 23, 2019 

Chronic Wasting Disease CWD TSE Prion and THE FEAST 2003 CDC an updated review of the science 2019 


TUESDAY, NOVEMBER 04, 2014 

Six-year follow-up of a point-source exposure to CWD contaminated venison in an Upstate New York community: risk behaviours and health outcomes 2005–2011 Authors, though, acknowledged the study was limited in geography and sample size and so it couldn't draw a conclusion about the risk to humans. They recommended more study. Dr. Ermias Belay was the report's principal author but he said New York and Oneida County officials are following the proper course by not launching a study. "There's really nothing to monitor presently. No one's sick," Belay said, noting the disease's incubation period in deer and elk is measured in years. " 


Transmission Studies Mule deer transmissions of CWD were by intracerebral inoculation and compared with natural cases {the following was written but with a single line marked through it ''first passage (by this route)}....TSS resulted in a more rapidly progressive clinical disease with repeated episodes of synocopy ending in coma. One control animal became affected, it is believed through contamination of inoculum (?saline). Further CWD transmissions were carried out by Dick Marsh into ferret, mink and squirrel monkey. Transmission occurred in ALL of these species with the shortest incubation period in the ferret. 

snip.... 


Prion Infectivity in Fat of Deer with Chronic Wasting Disease▿ 

Brent Race#, Kimberly Meade-White#, Richard Race and Bruce Chesebro* + Author Affiliations In mice, prion infectivity was recently detected in fat. Since ruminant fat is consumed by humans and fed to animals, we determined infectivity titers in fat from two CWD-infected deer. Deer fat devoid of muscle contained low levels of CWD infectivity and might be a risk factor for prion infection of other species. 

 
Prions in Skeletal Muscles of Deer with Chronic Wasting Disease Here bioassays in transgenic mice expressing cervid prion protein revealed the presence of infectious prions in skeletal muscles of CWD-infected deer, demonstrating that humans consuming or handling meat from CWD-infected deer are at risk to prion exposure. 


 *** now, let’s see what the authors said about this casual link, personal communications years ago, and then the latest on the zoonotic potential from CWD to humans from the TOKYO PRION 2016 CONFERENCE. see where it is stated NO STRONG evidence. so, does this mean there IS casual evidence ???? “Our conclusion stating that we found no strong evidence of CWD transmission to humans” 

From: TSS Subject: CWD aka MAD DEER/ELK TO HUMANS ??? 

Date: September 30, 2002 at 7:06 am PST 

From: "Belay, Ermias" 

To: Cc: "Race, Richard (NIH)" ; ; "Belay, Ermias" 

Sent: Monday, September 30, 2002 9:22 AM Subject: RE: TO CDC AND NIH - PUB MED- 3 MORE DEATHS - CWD - YOUNG HUNTERS 

Dear Sir/Madam, In the Archives of Neurology you quoted (the abstract of which was attached to your email), we did not say CWD in humans will present like variant CJD.. That assumption would be wrong. I encourage you to read the whole article and call me if you have questions or need more clarification (phone: 404-639-3091). 

Also, we do not claim that "no-one has ever been infected with prion disease from eating venison." Our conclusion stating that we found no strong evidence of CWD transmission to humans in the article you quoted or in any other forum is limited to the patients we investigated. 

Ermias Belay, M.D. Centers for Disease Control and Prevention 

-----Original Message----- From: 

Sent: Sunday, September 29, 2002 10:15 AM To: rr26k@nih.govrrace@niaid.nih.govebb8@CDC.GOV 

Subject: TO CDC AND NIH - PUB MED- 3 MORE DEATHS - CWD - YOUNG HUNTERS 

Sunday, November 10, 2002 6:26 PM .......snip........end..............TSS 

Thursday, April 03, 2008 

A prion disease of cervids: Chronic wasting disease 2008 1: Vet Res. 2008 Apr 3;39(4):41 A prion disease of cervids: Chronic wasting disease Sigurdson CJ. 

snip... *** twenty-seven CJD patients who regularly consumed venison were reported to the Surveillance Center***, 

snip... full text ; 


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

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

sporadic = 54,983 hits 


spontaneous = 325,650 hits 


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

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

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

> However, to date, no CWD infections have been reported in people.
key word here is ‘reported’. science has shown that CWD in humans will look like sporadic CJD. SO, how can one assume that CWD has not already transmitted to humans? they can’t, and it’s as simple as that. from all recorded science to date, CWD has already transmitted to humans, and it’s being misdiagnosed as sporadic CJD. …terry
*** LOOKING FOR CWD IN HUMANS AS nvCJD or as an ATYPICAL CJD, LOOKING IN ALL THE WRONG PLACES $$$ ***
*** These results would seem to suggest that CWD does indeed have zoonotic potential, at least as judged by the compatibility of CWD prions and their human PrPC target. Furthermore, extrapolation from this simple in vitro assay suggests that if zoonotic CWD occurred, it would most likely effect those of the PRNP codon 129-MM genotype and that the PrPres type would be similar to that found in the most common subtype of sCJD (MM1).***
CWD TSE PRION AND ZOONOTIC, ZOONOSIS, POTENTIAL

Subject: Re: DEER SPONGIFORM ENCEPHALOPATHY SURVEY & HOUND STUDY 

Date: Fri, 18 Oct 2002 23:12:22 +0100 

From: Steve Dealler 

Reply-To: Bovine Spongiform Encephalopathy Organization: Netscape Online member 

To: BSE-L@ References: 

Dear Terry,

An excellent piece of review as this literature is desperately difficult to get back from Government sites.

What happened with the deer was that an association between deer meat eating and sporadic CJD was found in about 1993. The evidence was not great but did not disappear after several years of asking CJD cases what they had eaten. I think that the work into deer disease largely stopped because it was not helpful to the UK industry...and no specific cases were reported. Well, if you dont look adequately like they are in USA currenly then you wont find any!

Steve Dealler 

====


''The association between venison eating and risk of CJD shows similar pattern, with regular venison eating associated with a 9 FOLD INCREASE IN RISK OF CJD (p = 0.04).''

CREUTZFELDT JAKOB DISEASE SURVEILLANCE IN THE UNITED KINGDOM THIRD ANNUAL REPORT AUGUST 1994

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

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

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

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

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

The association between venison eating and risk of CJD shows similar pattern, with regular venison eating associated with a 9 FOLD INCREASE IN RISK OF CJD (p = 0.04).

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

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

snip...

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

snip...

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

snip...

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

snip...see full report ;




Stephen Dealler is a consultant medical microbiologist deal@airtime.co.uk 

BSE Inquiry Steve Dealler

Management In Confidence

BSE: Private Submission of Bovine Brain Dealler

snip...see full text;

MONDAY, FEBRUARY 25, 2019

***> MAD DOGS AND ENGLISHMEN BSE, SCRAPIE, CWD, CJD, TSE PRION A REVIEW 2019


***> ''The association between venison eating and risk of CJD shows similar pattern, with regular venison eating associated with a 9 FOLD INCREASE IN RISK OF CJD (p = 0.04).''

***> 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.<*** 

***> 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) <***


***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.


TUESDAY, MAY 11, 2021

> A Unique Presentation of Creutzfeldt-Jakob Disease in a Patient Consuming Deer Antler Velvet <

Conclusion

We believe that our patient’s case of CJD is highly suspicious for cervid etiology given the circumstances of the case as well as the strong evidence of plausibility reported in published literature. This is the first known case of CJD in a patient who had consumed deer antler velvet. Despite the confirmed diagnosis of CJD, a causal relationship between the patient’s disease and his consumption of deer antler velvet cannot be definitively concluded.

Supplemental data including molecular tissue sample analysis and autopsy findings could yield further supporting evidence. Given this patient’s clinical resemblance to CBD and the known histological similarities of CBD with CJD, clinicians should consider both diseases in the differential diagnosis of patients with a similarly esoteric presentation. Regardless of the origin of this patient’s disease, it is clear that the potential for prion transmission from cervids to humans should be further investigated by the academic community with considerable urgency.


''We believe that our patient’s case of CJD is highly suspicious for cervid etiology given the circumstances of the case as well as the strong evidence of plausibility reported in published literature. This is the first known case of CJD in a patient who had consumed deer antler velvet. Despite the confirmed diagnosis of CJD, a causal relationship between the patient’s disease and his consumption of deer antler velvet cannot be definitively concluded.''


CREUTZFELDT JAKOB DISEASE: A Unique Presentation of Creutzfeldt-Jakob Disease in a Patient Consuming Deer Antler Velvet

i was warning England and the BSE Inquiry about just this, way back in 1998, and was ask to supply information to the BSE Inquiry. for anyone that might be interested, see;

Singeltary submission to the BSE Inquiry on CJD and Nutritional Supplements 1998

ABOUT that deer antler spray and CWD TSE PRION... I have been screaming this since my neighbors mom died from cjd, and she had been taking a supplement that contained bovine brain, bovine eyeball, and other SRMs specified risk materials, the most high risk for mad cow disease. just saying...

I made a submission to the BSE Inquiry long ago during the BSE Inquiry days, and they seemed pretty interested.

Sender: "Patricia Cantos"

To: "Terry S Singeltary Sr. (E-mail)"

Subject: Your submission to the Inquiry

Date: Fri, 3 Jul 1998 10:10:05 +0100 3 July 1998

Mr Terry S Singeltary Sr. E-Mail: Flounder at wt.net Ref: E2979

Dear Mr Singeltary, Thank you for your E-mail message of the 30th of June 1998 providing the Inquiry with your further comments. Thank you for offering to provide the Inquiry with any test results on the nutritional supplements your mother was taking before she died. As requested I am sending you our general Information Pack and a copy of the Chairman's letter. Please contact me if your system cannot read the attachments. Regarding your question, the Inquiry is looking into many aspects of the scientific evidence on BSE and nvCJD.

I would refer you to the transcripts of evidence we have already heard which are found on our internet site at ;

http://www.bse.org.uk.

Could you please provide the Inquiry with a copy of the press article you refer to in your e-mail? If not an approximate date for the article so that we can locate it? In the meantime, thank you for you comments. Please do not hesitate to contact me on... snip...end...tss

everyone I tell this too gets it screwed up...MY MOTHER WAS NOT TAKING THOSE SUPPLEMENTS IPLEX (that I ever knew of). this was my neighbors mother that died exactly one year previously and to the day of sporadic CJD that was diagnosed as Alzheimer’s at first. my mother died exactly a year later from the Heidenhain Variant of Creutzfeldt Jakob Disease hvCJD, and exceedingly rare strains of the ever growing sporadic CJD’s. both cases confirmed. ...

kind regards, terry

TSEs i.e. mad cow disease's BSE/BASE and NUTRITIONAL SUPPLEMENTS IPLEX, mad by standard process; vacuum dried bovine BRAIN, bone meal, bovine EYE, veal Bone, bovine liver powder, bovine adrenal, vacuum dried bovine kidney, and vacuum dried porcine stomach. also; what about potential mad cow candy bars ? see their potential mad cow candy bar list too... THESE are just a few of MANY of just this ONE COMPANY...TSS

''So, in sum, dietary supplements sold in the United States often contain ruminant tissues from undisclosed sources. Personally, I am rather squeamish and I don't think I would be eating prostate or testicle or pituitary, but I am also a little bit wary of consuming products with those glands, not just out of personal repugnance but simply out of a health concern.'' DEPARTMENT OF HEALTH AND HUMAN SERVICES FOOD AND DRUG ADMINISTRATION CENTER FOR BIOLOGICS EVALUATION AND RESEARCH TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES ADVISORY COMMITTEE Friday, January 19, 2001

snip...

15 Open Public Hearing

16 DR. FREAS: We are opening the open public hearing

17 now. We have received one response to speak in this

18 afternoon's open public hearing. That is from Dr. Scott

19 Norton. If Dr. Norton is here, would you please come

20 forward. You can either use the podium or the microphone,

21 whichever is your choice.

22 DR. NORTON: I am Scott Norton and I am a

23 physician in the Washington D.C. area. I am here speaking

24 as a private citizen today.

25 I first became concerned about the presence of 231

1 tissues from ruminant animals in dietary supplements about

2 six months ago and expressed my concern in a letter that was 3 published in New England Journal of Medicine in July of Year 4 2000. 5 A couple of the products that I had looked at, and 6 examined their labels, that raised these concerns I brought 7 in right here. I will just read some of the organs that are 8 found in one that is called Male Power. Deer antler, 9 pancreas, orchic--despite what we just heard that the FDA

10 prefers the term "testicular tissue" to be written on the

11 labels, I have never seen a dietary supplement say

12 "testicle." They always say "orchis" or "orchic" which may

13 sound rather flowery to the etymologically impaired--thymus,

14 adrenal, heart, lymph node, prostate, spleen and pituitary.

15 There are actually seventeen organs in that particular

16 product.

17 There is another product that is called Brain

18 Nutrition that tells us that it is vitamins and minerals

19 essential for important brain function. It does not mention

20 that there is any glandulars on at least the bold print. 21 But if you look at the small print on the back, we learn

22 that it has brain extract and pituitary extract, raw, in

23 there.

24 We know that many of the organs that can be found

25 in the dietary supplements do fall in that list of organs

232

1 that are suspect for contamination with TSEs, the labels, in 2 nearly all cases, identify neither the animal source nor the 3 geographic location from which the organs were derived. I 4 have seen one line that did specify from New Zealand cattle 5 but no other manufacturer will list either the species or 6 the geographic location. 7 The FDA's and the USDA's import alerts that we 8 just learned about prohibit the use of these organs in 9 foods, medicines and medical devices. But my reading of the

10 alert, 17-04, suggests that DSHEA does allow some loopholes

11 for these tissues to possible slip in.

12 I will just read from 17-04 that we heard. On the

13 first page, it says that, "This alert does not establish any

14 obligations on regulated entities." I love seeing

15 legislation that starts out with that caveat.

16 Then it says, further, "The USDA regulations do

17 not apply to bovine-derived materials intended for human

18 consumption as finished dietary supplements." We also learn

19 that the prohibition, or the import alert, is limited to

20 bulk lots of these tissues, completed tissues, from BSE-

21 derived countries. It does not mention if it is not a bulk

22 import or if it is raw materials rather than finished

23 materials.

24 Further, we know that it is strongly recommended

25 but not actually prohibited in the language here. So I have

233

1 not taken the assurances from that import alert that Dr. 2 Moore was trying to convey to us. 3 So, in sum, dietary supplements sold in the United 4 States often contain ruminant tissues from undisclosed 5 sources. Personally, I am rather squeamish and I don't 6 think I would be eating prostate or testicle or pituitary, 7 but I am also a little bit wary of consuming products with 8 those glands, not just out of personal repugnance but simply 9 out of a health concern.

10 So my question to the advisory committee is this;

11 is my caution reasonable and, if it is, should we take

12 further efforts to inform, or even protect, the American

13 public from such exposure.

14 I was curious about Dr. Moore's remarks. I sensed

15 two messages. One was the initial reassurance that FDA has

16 the regulatory authority but then I also learned that it is

17 the manufacturer's responsibility to provide those 18 assurances, that the FDA doesn't actually inspect.

19 I think that the FDA commissioners from Harvey

20 Wylie to David Kessler would say that that track record has

21 proven itself.

22 Thank you very much.

23 [Applause.]

24 DR. BROWN: Thanks, Dr. Norton. 25 Committee Discussion snip...

17 But I think that we could exhibit some quite 18 reasonable concern about blood donors who are taking dietary 19 supplements that contain a certain amount of unspecified- 20 origin brain, brain-related, brain and pituitary material. 21 If they have done this for more than a sniff or something 22 like that, then, perhaps, they should be deferred as blood 23 donors. 24 That is probably worse than spending six months in 25 the U.K. 1/19/01 3681t2.rtf(845) page 501 http://www.fda.gov/ohrms/dockets/ac/cber01.htm

Advisory Committees: CBER 2001 Meeting Documents

see actual paper;




-------- Original Message --------

Subject: METABOLIFE AND TSEs GAO-03-494 ''URGENT DATA''

Date: Thu, 01 May 2003 11:23:01 -0500

From: "Terry S. Singeltary Sr."

To: NelliganJ at gao.gov

The General Accounting Office (GAO) today released the following reports and testimonies:

REPORTS

1. Dietary Supplements: Review of Health-Related Call Records for Users of Metabolife 356. GAO-03-494, March 31.



see updated url link;


GREETINGS GAO:

i was surprised that i did not see any listing of bovine tissue in metabolife on it's label. have they ceased using these desiccated tissues???

i see that the lable on this product METABOLIFE 356, does not state that it has any tissues of desiccated bovine organs? i no the product use to, so i am curious if they have ceased the use of the tissues of cattle they use to use (see below)???

METABOLIFE 356 BOVINE COMPLEX/GLANDULAR SYSTEM OVARIES, PROSTATE, SCROTUM AND ADRENAL USDA SOURCE CATTLE

i tried warning them years ago of this potential threat of CJD/TSEs;

From: Randy Smith To: "'flounder at wt.net'" Subject: Metabolife Date: Mon, 7 Dec 1998 14:21:35 -0800

Dear Sir,

We are looking at reformulation. I agree that slow virus diseases present a problem in some areas of the world.

Our product uses healthy USDA inspected cattle for the glandular extract.

If you have any links to more information on this subject I would like to examine them.

Thank you for your interest and concern,

Dr. Smith ============

snip...

see full text links of this archived information ;




with that, there is abundance of other scientific studies that show it's very likely CWD will or already has, transmit to humans, it's just that no one wants to believe it, they simply don't want it to happen, neither do i, but in the real world, imo, it's already happened and is being masked as sporadic CJD imo, you can see this science archived here, skroll down to about the halfway point of this blog on the recent cases of cwd in Texas;

see about half way down to;

***> PRION CONFERENCE 2022 ABSTRACTS CWD TSE PrP ZOONOSIS

Chronic Wasting Disease in Texas

A Real Disease with Proven Impacts

Produced by a coalition of concerned hunters, landowners, & conservationists (last update 08/2023)

Snip…

Since 2012, CWD has been detected in wild deer in just 7 counties in Texas and is only established in the western panhandle and far west Texas.

In that same period of time, captive deer breeders have exposed almost half of Texas counties to CWD. 

Deer held in captive breeding facilities are confined to much tighter spaces, and have intimate contact with many more animals on a daily basis. By far the greatest factor in amplifying the spread of CWD is the artificial movement of these animals, shipped in livestock trailers hundreds of miles, far outside of their natural home range, and ultimately released to co-mingle with wild deer. 

Each year, Texas captive deer breeders liberate 20,000-30,000 deer from their pens to the wild. 

For every deer breeding facility where a CWD positive deer is discovered, an epidemiological investigation is conducted by the Texas Parks & Wildlife Department and the Texas Animal Health Commission to determine how many other deer may have been exposed to the disease and where they have been shipped. Because of the prolific artificial movement of captive deer, one deer with CWD can impact hundreds of other facilities and ranches across the state.

Unfortunately, released deer in Texas are not required to retain any kind of visible identification (an ear tag), and for this reason, the vast majority of released deer cannot be relocated for testing. 

As of August 2023, 116 Texas counties have received possibly infected breeder deer that cannot be located, putting more than 140,000 landowners at risk of the disease. 

Snip

The state of Texas has been testing for CWD since 2002. Since that time, more than 302,360 captive and free range deer have been tested. 

From 2015-2022, more than 127,000 samples were collected from hunter-harvested and roadkill deer. This sampling rate and risk-based distribution provides scientists confidence that they would have detected the disease if it existed at a very low prevalence (<1%) in any given region at the time sampling began.

Snip…

We have learned from other states where CWD has been present the longest, that a constant increase in the prevalence of the disease may lead to a significant decline in the deer population. When disease prevalence exceeds 20%, deer populations have declined by up to 50%. In some areas of Colorado, where CWD has been present since 1985, mule deer abundance has declined by 45% since that time, despite adequate habitat and no hunting ( Miller et al. 2008 ). Similarly, the South Converse Game Unit in Wyoming has documented CWD prevalence exceeding 50% and has seen an approximate 50% decline in mule deer populations.

Snip…

Rural Economies

Deer hunting is the lifeblood of rural Texas. White-tailed deer hunting is by far the most impactful segment of the hunting economy, representing $4.3 billion, according to a recent Texas A&M Study. And while deer breeders represent a very small segment of that economy (less than 5%), they represent one of the greatest risks. ( Full Texas A&M Report )

Real Estate

Rural land prices are largely driven by recreational buyers with hunting as a top land amenity. Without deer hunting, many of these properties will be worth much less.

Conservation Funding

Deer hunters are the largest funders of wildlife conservation in Texas through excise taxes on firearms, ammunition, and gear along with active membership supporting and funding conservation organizations. If deer hunting suffers due to CWD, all wildlife in Texas lose.

Culture & Health

Texas’ native deer herd has iconic value for all Texans. Deer hunting brings families together, creates camaraderie in communities, and serves to connect Texans to nature. There is no better protein than wild, locally harvested, non-GMO and totally organic venison. A healthy deer herd leads to healthy Texans and a healthy and prosperous Texas. 

Snip…

This isn't a disease for our lifetime. It's a disease for our grandchildren's lifetime. 

 - Dr. Bob Dittmar, Former Texas State Wildlife Veterinarian 

Snip…

See the full text with maps, graphs, much more, excellent data…


Since 2012, CWD has been detected in wild deer in just 7 counties in Texas and is only established in the western panhandle and far west Texas.

In that same period of time, captive deer breeders have exposed almost half of Texas counties to CWD. 


As of August 2023, 116 Texas counties have received possibly infected breeder deer that cannot be located, putting more than 140,000 landowners at risk of the disease. 


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


 Counties where CWD Exposed Deer were Released 


 Number of CWD Exposed Deer Released by County 


Chronic Wasting Disease CWD Captive Herds updated April 2023 


Chronic Wasting Disease CWD Captive Herds updated April 2023 


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.


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...


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.''


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). 


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. 


“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.”


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.”


TEXAS CHRONIC WASTING DISEASE RISES SUBSTANTIALLY TO 575 CONFIRMED CWD CASES TO DATE (THIS PAGE IS VERY OUTDATED...terry)


FRIDAY, DECEMBER 08, 2023 

TEXAS CWD TSE PRION DIRE CONSEQUENCES ARE HERE! 


***> CHRONIC WASTING DISEASE CWD TSE PRION BY STATE UPDATE END OF YEAR 2023 <***


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

Reports

Report of the Subcommittee on Farmed Cervidae

The Subcommittee on Farmed Cervidae met on October 26, 2015.


REPORT OF THE COMMITTEE ON CAPTIVE WILDLIFE AND ALTERNATIVE LIVESTOCK CWD 2016


REPORT OF THE COMMITTEE ON CAPTIVE WILDLIFE AND ALTERNATIVE LIVESTOCK CWD 2017

snip...

Update on CWD Ante-mortem Testing-Texas and Wisconsin 

Scott Bugai, Private Practitioner 

Dr. Bugai’s presentation explained there are four ante-mortem diagnostic tests for transmissible spongiform encephalopathies (TSEs) prion diseases: 1) Nictitating membrane, or “third eyelid,” biopsy; 2) Palatine tonsillar lymphoid tissue biopsy (tonsil biopsy); 3) Rectoanal mucosa-associated lymphoid tissue (RAMALT) biopsy (rectal biopsy) and 4) Medial Retropharyngeal Lymph Node Biopsy. 

IHC in tonsillar lymphoid tissue. Sensitivity = 97.3% and Specificity = 100%

Total CWD Testing in Texas Since Finding CWD in 2012: 

• TPWD Tests: 36,215 and Other/Private Tests: 82,222= Total Tests: 118,437 (This includes postmortem and live testing).

• Total Live Testing in Texas Since Rule Implementation: TPWD Live Tests: 178 and Other/Private Tests: 24,255= Total Tests: 24,433

Total CWD Positives in Texas: Free Range: 18 and Captive Cervid: 33= Total Positives: 51

• Total CWD Tests Since Finding Disease: Total Tests: 118,437

• Estimated CWD Prevalence: .04%

Cervid Health Update-Status of Updated CWD Standards, TB/Brucellosis Rule


REPORT OF THE COMMITTEE ON CAPTIVE WILDLIFE AND ALTERNATIVE LIVESTOCK CWD 2018


REPORT OF THE COMMITTEE ON CAPTIVE WILDLIFE AND ALTERNATIVE LIVESTOCK CWD 2019

Cervid Health Update- Status of Updated CWD Standards, TB/Brucellosis Rule, Overview of CWD Nationwide

Dr. Tracy Nichols, USDA-APHIS VS

Dr. Nichols provided an overview of the voluntary Chronic Wasting Disease Herd Certification Program. The revised CWD Standards was published in May 2019 and now in effect. There are 28 states participating in the Chronic Wasting Disease Herd Certification Program, which includes 2,100 enrolled cervid herds with over 1,700 currently certified. 17 new cervid herds were identified with CWD in FY 2019.


REPORT OF THE COMMITTEE ON CAPTIVE WILDLIFE AND ALTERNATIVE LIVESTOCK CWD 2020

Presentations and Reports

USDA-APHIS-VS Annual Update from the Cervid Health Team

Tracy Nichols, Animal and Plant Health Inspection Service (APHIS), Veterinary Services (VS)

Fiscal Year (FY) 2020

Voluntary Chronic Wasting Disease Herd Certification Program (HCP)

The APHIS HCP was implemented in 2014. It is a voluntary Federal-State-industry cooperative program administered by APHIS and implemented by participating States. The program provides uniform national herd certification standards that minimize the risk of spreading chronic wasting disease (CWD) in farmed cervid populations. Participating States and herd owners must comply with requirements for animal identification, fencing, recordkeeping, inspections/inventories, as well as animal mortality testing and response to any CWD-exposed, suspect, and positive herds. APHIS monitors the Approved State HCPs to ensure consistency with Federal standards through annual reporting by the States.

The current Cervid Health Program staff officers are as follows: Mark Lyons, Jennifer Siembieda, and Tracy Nichols

Voluntary Herd Certification Participation Summary

 Currently, 28 States participate in the voluntary CWD Herd Certification Program, encompassing 2,145 enrolled herds, of which, 1,723 had the certified status in the program.

 1,616 enrolled deer herds, of which, 1,297 were certified

 371 enrolled elk herds, of which, 328 were certified

 147 enrolled mixed species herds, of which, 98 were certified

CWD in Farmed Cervids

 There were 22 newly identified CWD positive herds in FY20

 13 of these herds were not participants in the Federal HCP

 2 herds were considered enrolled in the HCP

 7 herds were certified in the HCP

 Half of the herds were located within 20 miles of identified CWD in the wild, half were not

CWD Herds by State

Pennsylvania: Eight new CWD positive herds

 Breeding herd of 33 WTD, HCP certified, depopulated with Federal indemnity

 Breeding herd of 6 WTD, not in HCP, depopulated with Federal indemnity

 Breeding herd of 15 WTD, not in HCP, depopulated by owner

 Hunt preserve of 58 WTD, not in HCP, populated and under quarantine

 Breeding herd of 75 WTD, not in HCP, populated and under quarantine

 Breeding herd of WTD, not in HCP, populated and under quarantine

 Breeding herd of 90 WTD, not in HCP, populated and under quarantine

 Breeding herd of 4 WTD, not in HCP, populated and under quarantine

Iowa: Two new CWD positive herds

 Breeding herd of 23 WTD, HCP certified, depopulated with Federal indemnity

 Breeding herd of 13 WTD, HCP certified, depopulated with Federal indemnity

Minnesota: Two new CWD positive herds

 Breeding herd of 3 WTD, enrolled in HCP, not certified, depopulated by owner

 Breeding herd of 6 WTD, enrolled in HCP, not certified, depopulated with Federal indemnity

Colorado: Two new CWD positive herds

 Breeding herd/hunt preserve of 9 elk, HCP certified, depopulated by owner

 Breeding herd of 8 elk, HCP certified, populated and under quarantine

Utah: Two new CWD positive herds

 Breeding herd of 465 elk, not in HCP, partial depopulation with Federal indemnity removed purchased animals, populated-quarantine

 Breeding herd of 103 elk, not in HCP, partial depopulation with Federal indemnity removed purchased animals, populated-quarantine

Michigan: One new CWD positive herd

 Hunt preserve of >600 WTD, not in HCP, populated and under quarantine

Montana: One new CWD positive herd

 Breeding herd of 3 elk, not in HCP, populated and under quarantine

Texas: one new CWD positive herd

 Breeding herd of 59 WTD, not in HCP, depopulated with Federal indemnity

Kansas: One new CWD positive herd

 Breeding herd of 20 elk, HCP certified, depopulated with Federal indemnity

Ohio: Eight new CWD positive herd

 Breeding herd of 138 WTD, HCP certified, depopulated with Federal indemnity

Research

 Whole genome study investigating the association of genetics with CWD susceptibility has been published.

 Blinded validation of the genetic predicative model is almost complete.

 A standardized protocol has been developed, in partnership with Agricultural Research Service (ARS), United States Geological Survey (USGS), University of Wisconsin, and National Institutes of Health (NIH) for tissue sample testing using real-time quaking-induced conversion (RT-QuIC).

 A study is starting shortly to determine the sensitivity and specify of RT-QuIC utilizing the standardized protocol.

snip...


REPORT OF THE COMMITTEE ON CAPTIVE WILDLIFE AND ALTERNATIVE LIVESTOCK CWD 2021

Presentations and Reports

2021 USAHA Cervid Section Summary USDA-APHIS-VS Cervid Health Program

Tracy Nichols, USDA, Animal and Plant Health Inspection Service (APHIS)

FY2021 CWD Detections in Farmed Cervids: There were 35 new chronic wasting disease (CWD) positive farmed cervid herds in FY21 (31 white-tailed deer, 1 elk, 3 mixed species herds). Twenty-three of the herds were not participants in the Federal Herd Certification Program (HCP), four were enrolled, but not certified, in the HCP, and eight were certified in the HCP. Twenty-one of the 35 newly identified herds were in areas where CWD has been found within 20 miles in wild cervid populations. 

***> While resistant alleles have been identified in cervids, a PRNP variant that completely prevents CWD has not yet been identified. 

Thus, control of the disease in farmed herds traditionally relies on quarantine and depopulation. 


REPORT OF THE COMMITTEE ON CAPTIVE WILDLIFE AND ALTERNATIVE LIVESTOCK CWD 2022

Three presentations were given during the October 10, 2022 meeting. The following presentation summaries were given starting in order at number one:

1. Dr. Tracy Nichols, PhD, USDA /APHIS Fort Collins, CO

2022 USAHA Cervid Section Summary USDA APHIS VS Cervid Health Program

FY2022 CWD Detections in Farmed Cervids: There were 23 new CWD positive farmed cervid herds in FY 22 (18 white-tailed deer, 3 elk, 2 mixed species herds). Fifteen of the herds were not participants in the Federal Herd Certification Program (HCP), two were enrolled, but not certified, in the HCP, and six were certified in the HCP. Nineteen of the 23 newly identified herds were in areas where CWD has been found within 20 miles in wild cervid populations. 



''Dr. Anderson presented a draft rewrite of the CWD Program Standards that supports the requirements specified in 9 CFR 55 and 81 and outlines a program to control CWD in farmed cervid herds without causing unnecessary harm to cervid producers.''

Camel prion disease: a new emerging disease in North Africa Update 2024

KEYNOTE 1

Camel prion disease: a new emerging disease in North Africa

Authors: Laura Pirisinu3 , Amara Abdelkader1 , Babelhadj Baaissa2 , Di Bari Michele Angelo3 , Bruno Rosalia3 , Chiappini Barbara3 , Vanni Ilaria3 , Nonno Romolo3 , Agrimi Umberto3 , Vaccari Gabriele3 , Pirisinu Laura3

1 Ecole Nationale de Médecine Vétrinaire de Sidi Thabet, Université Mannouba, Tunis, Tunisia 2 École Normale Supérieure Ouargla, Ouargla, Algeria 3 Istituto Superiore di Sanità, Department of Food safety, Nutrition and Veterinary Public Health, Rome, Italy Corresponding author: laura.pirisinu@iss.it

In 2018, a new prion disease was identified in dromedary camels in Algeria and later in Tunisia, and named camel prion disease (CPrD).

Evidences obtained from passive surveillance in Algeria as well as the involvement of lymphoid tissue in CPrD pathogenesis concurred in suggesting the contagious nature of this disease, with potential impact on animal and human health.

The world camel population is estimated at almost 39 million heads, 87% of which is found in Africa. Dromedary husbandry is widespread throughout North and Central Africa, the Middle East, Asia and Australia. In some areas intensive camel farming is rapidly increasing. Camels represent vital sources of meat, milk and transportation for millions of people living in the most arid regions of the world. The emergence of a prion disease in a new species and in new geographical areas requires attention and investigations for understanding the characteristics, the origin and ecology of the disease and the risks in both animals and humans.

The available evidences will be discussed in light of their contribution to understanding the nature of CPrD and developing control strategies to limit its spread in animals and minimise human exposure.

=====

POSTER A7 – Lymphoid tropism of prions in dromedary camels

Authors: Rosalia Bruno 1 *, Baaissa Babelhadj 2 *, Laura Pirisinu1 , Geraldina Riccardi 1 , Romolo Nonno 1 , Umberto Agrimi 1

, Gabriele Vaccari 1 and Michele Angelo Di Bari 1 1 Department of Food Safety, Nutrition and Veterinary Public Health; Italian National Institute of Health; Rome, Italy. 2 Ecole Normale Superieure Ouargla Laboratoire de Protection des Écosystèmes en Zones Arides et Semi Arides University Kasdi Merbah Ouargla, Algeria. Corresponding author: rosalia.bruno@iss.it

Camel prion disease (CPrD) is an emerging disease of dromedary camels. We have previously shown PrPSc deposition in a lymph node of a CPrD-affected dromedary (Babelhadj et al. 2018). Here, we investigated the presence of PrPSc in lymph nodes, spleen, Peyer’s patches and RAMALT in four symptomatic (CNS+) and one asymptomatic (CNS-) Algerian dromedaries. We detected PrPSc deposition in all lymphoid tissues analyzed, regardless of the clinical status. Our results confirm the lymphoid tropism of CPrD and suggest that lymphoid involvement precedes neuroinvasion in CPrD, similarly to contagious TSEs such as classical scrapie and CWD.

=====

POSTER A11 – Neuropathological characterization of camel prion disease

Authors: Michele Angelo Di Bari1 , Baaissa Babelhadj2 , Geraldina Riccardi1 , Rosalia Bruno1 , Romolo Nonno1 , Umberto Agrimi1 , Gabriele Vaccari1 and Laura Pirisinu1

1 Istituto Superiore di Sanità Department of Food Safety, Nutrition and Veterinary Public Health, Rome, Italy 2 Ecole Normale Superieure Ouargla Laboratoire de Protection des Écosystèmes en Zones Arides et Semi Arides University Kasdi Merbah Ouargla, Ouargla, Algeria Corresponding author: michele.dibari@iss.it

In 2018, we described and designed as Camel prion disease (CPrD), a novel prion disease in dromedary camel in Algeria. Herein, we present a detailed neuropathological description of the phenotype of CPrD, in terms of both spongiform change and PrPSc accumulation. The analysis of the brain of eleven CPrD cases from Algeria revealed widespread vacuolation and PrPSc deposition in subcortical areas, cerebellum and caudal brainstem, while cortices were variably affected. This study highlighted a homogeneous disease phenotype among the dromedary cases analyzed and allowed us to define the brain regions relevant for the neuropathological diagnosis of CPrD.


Friday, May 12, 2023

Camel prion disease, a new emerging disease in North Africa, Lymphoid Tropism, Neuropathological Characterization Update 2023

11th Iberian Congress on Prions Barcelona 2023






Monday, November 13, 2023

Food and Drug Administration's BSE Feed Regulation (21 CFR 589.2000) Singeltary Another Request for Update 2023


FRIDAY, DECEMBER 22, 2023

The Mad Cow That Stole Christmas, 20 Years Later

The Mad Cow That Stole Christmas, 20 Years Later, What Has Changed, Nothing

THE USA has systematically covered up mad cow disease, in my honest opinion, the USA mad cow disease today, is Chronic Wasting Disease CWD TSE Prion disease in Cervid, they can't cover that up. 


PLEASE NOTE, CJD IS NOW 1 IN 5,000 GLOBALLY, COLLINGE ET AL 2023!

Professor John Collinge on tackling prion diseases, sCJD accounts for around 1 in 5000 deaths worldwide

MONDAY, SEPTEMBER 11, 2023 

Professor John Collinge on tackling prion diseases “The best-known human prion disease is sporadic Creutzfeldt-Jakob disease (sCJD), a rapidly progressive dementia which accounts for around 1 in 5000 deaths worldwide.” There is accumulating evidence also for iatrogenic AD. Understanding prion biology, and in particular how propagation of prions leads to neurodegeneration, is therefore of central research importance in medicine.



MONDAY, DECEMBER 18, 2023

Change in Epidemiology of Creutzfeldt-Jakob Disease in the US, 2007-2020


TUESDAY, DECEMBER 12, 2023 

CREUTZFELDT JAKOB DISEASE TSE PRION DISEASE UPDATE USA DECEMBER 2023 


GOOD LUCK!

wasted days and wasted nights...FREDDY FENDER

Terry S. Singeltary Sr. flounder9@verizon.net