Chronic Wasting Disease: Exposure Risk of Chronic Wasting Disease in Humans

Exposure Risk of Chronic Wasting Disease in Humans

by Satish K. Nemani 1,2,Jennifer L. Myskiw 3,4,Lise Lamoureux 3,Stephanie A. Booth 3,4 andValerie L. Sim 1,2,*OrcID

1 Centre for Prions and Protein Folding Diseases, Edmonton, AB T6G 2R3, Canada

2 Department of Medicine, Division of Neurology, University of Alberta, Edmonton, AB T6G 2R3, Canada

3 Zoonotic Diseases and Special Pathogens, Public Health Agency of Canada, National Microbiology Laboratory, Winnipeg, MB R3E 3R2, Canada

4 Department of Medical Microbiology and Infectious Diseases, Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3E 3R2, Canada

* Author to whom correspondence should be addressed.

Academic Editor: Byron Caughey

Viruses 2020, 12(12), 1454; https://doi.org/10.3390/v12121454

Received: 1 December 2020 / Revised: 14 December 2020 / Accepted: 15 December 2020 / Published: 17 December 2020

(This article belongs to the Special Issue The Future of the Chronic Wasting Disease Epizootic)

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Abstract

The majority of human prion diseases are sporadic, but acquired disease can occur, as seen with variant Creutzfeldt–Jakob disease (vCJD) following consumption of bovine spongiform encephalopathy (BSE). With increasing rates of cervid chronic wasting disease (CWD), there is concern that a new form of human prion disease may arise. Currently, there is no evidence of transmission of CWD to humans, suggesting the presence of a strong species barrier; however, in vitro and in vivo studies on the zoonotic potential of CWD have yielded mixed results. The emergence of different CWD strains is also concerning, as different strains can have different abilities to cross species barriers. Given that venison consumption is common in areas where CWD rates are on the rise, increased rates of human exposure are inevitable. If CWD was to infect humans, it is unclear how it would present clinically; in vCJD, it was strain-typing of vCJD prions that proved the causal link to BSE. Therefore, the best way to screen for CWD in humans is to have thorough strain-typing of harvested cervids and human CJD cases so that we will be in a position to detect atypical strains or strain shifts within the human CJD population. Keywords: chronic wasting disease (CWD); zoonotic potential; bovine spongiform encephalopathy (BSE); variant Creutzfeldt–Jakob disease (vCJD); sporadic CJD; CWD prions (PrPCWD); proteinase K resistant prion protein (PK-resPrP); strains; PRNP polymorphism; 129M/V polymorphism

1. Introduction

Prion diseases are fatal transmissible neurodegenerative diseases thought to be caused by conformational conversion of cellular prion protein (PrPC) to pathological prion protein (PrPD) and its accumulation in both humans and animals [1]. In humans, prion diseases are categorized into three different forms: sporadic, genetic and acquired [2,3]. While sporadic Creutzfeldt–Jakob disease (sCJD) is the most prevalent form of human prion diseases, the acquired forms have generated a lot of fear, in particular over concern of zoonotic transmission through consumption of infected animals. The animal prion diseases comprise scrapie in small ruminants [1,4], bovine spongiform encephalopathy (BSE) in cattle [5], transmissible mink encephalopathy (TME) in mink [6], feline spongiform encephalopathy (FSE) in cats [7], spongiform encephalopathy in camels [8] and chronic wasting disease (CWD) in cervids [9]. Zoonotic transmission is a theoretical concern for all prion diseases, but, to date, the only documented transmission to humans has been from BSE-infected cattle. In the late 1980s, the outbreak of BSE (or mad cow disease) in cattle, and its transmission to humans through the food supply, resulted in a new form of prion disease, called variant CJD (vCJD), and caused 231 human deaths [10,11]. This has raised a concern for zoonotic transmission of other animal prion diseases, in particular CWD, as prevalence of this prion disease is rising.

CWD was first described in 1967 in a captive mule deer and later identified in black-tailed deer and Rocky Mountain elk in wild-life farms in Colorado and Wyoming [9,12]. In 2001, CWD was described in white-tailed deer in Nebraska and Dakota [13], and, in 2005, it was described in moose in Colorado [14]. Recently, CWD was also described in reindeer in Norway [15].

As the most infectious and contagious of all prion diseases, CWD is efficiently transmitted among cervids by both direct and environmental contacts [11]. Unlike BSE, CWD prions (PrPCWD) are distributed throughout the body of the diseased animal, including the peripheral and central nervous system, muscles, antler velvet and blood [16]. PrPCWD is also shed in saliva, feces and urine [11,17] and can persist in the environment for many years, increasing exposure risk to all animal species within the ecosystem. This shedding, plus the fact that CWD occurs in wild migrating animals, makes its management more challenging than BSE, where banning specific risk material or contaminated feed was sufficient to reduce cases [18,19]. Attempts to control CWD spread include non-selective culling of the animals in endemic areas, regulations on the number of animals to be raised in a farm, guidance on carcass handling, mandatory testing of hunter harvested animals, feed bans, and prohibitions in importing cervids [20]. Despite these measures, CWD incidence continues to rise.

A major concern for human exposure to CWD comes through direct consumption of venison, but also consumption of other ruminants that might be reservoirs of adapted CWD prions [21,22]. Fortunately, there is a strong species barrier in most prion diseases, largely dependent on the degree of homology of PrP amino acid sequence between donor and recipient species. The barrier is not absolute though; it can be influenced by PRNP polymorphisms and different prion strains [23,24]. This is highly relevant, as studies are demonstrating the existence of several different CWD strains, each of which may have unique transmission properties towards humans.

As an added challenge, we do not know what the signs and symptoms of CWD would look like in humans. It might resemble sporadic CJD or present as something unlike any known human prion disease. In cervids, clinical signs of CWD include weight loss, isolation, and loss of fear towards humans. Polyuria, polydipsia, excessive drooling, ataxia and tremors are observed during the later stages of the disease [25,26]. Among cervids, the incubation period varies from 2 to 4 years [27]; if transmitted to humans, it could be decades.

In this article, we will review factors that could influence the transmission of CWD to humans, including risk of exposure, the influence of PRNP polymorphism and CWD strain on the species barrier, and transmission data from theoretical, experimental, and real-world scenarios. We will also present current surveillance data on human cases of prion disease and discuss how we might detect human presentations of CWD, should they arise.

2. Risk of Exposure

Whether humans will succumb to CWD transmission depends, in part, on the risk of humans encountering CWD in the real world. Human exposure to high levels of CWD prions is most likely to occur through direct handling of infected cervid carcasses or meat byproducts and through consumption of venison, velvet or other cervid byproducts [28]. Unlike BSE, where prions existed primarily in brain and spinal cord, prions in CWD are found at higher titers in tissues that are more highly consumed, such as skeletal muscle, and have been detected in cervids that are still sub-clinical and therefore more likely to be consumed [16,29]. Environmental exposure of humans to CWD prions is also possible, given that PrPCWD is shed into the environment where it may remain infectious for decades. For these reasons, the prevalence of CWD and its geographical footprint are important factors.

Since the first description of CWD in the 1960s, there has been increasing geographic spread, with CWD now found in 26 states in the U.S., three provinces in Canada, South Korea, Norway, Sweden, and Finland [27,30]. In North America, the prevalence of CWD is variable, affecting up to 30% of free ranging animals in some areas, and as many as 80–90% of animals in captivity [26,27,31]. In Wisconsin, where prevalence of CWD is among the highest in the world, CWD cases in white-tailed deer doubled between 2010 and 2016, and male deer populations had prevalence of infection up to 40–50% with females at 20–30% [32]

3. PRNP Polymorphisms and Susceptibility After exposure risk, we need to consider how efficiently CWD can cross the species barrier into humans. The transmission barrier is dependent on the amino acid sequence of host PrPC and incoming misfolded PrPSc [24,33]. Therefore, polymorphisms of host PrPC can play a major role in susceptibility. In humans, one polymorphism plays the greatest role in susceptibility; for cervids, 16 polymorphisms have been reported, with five linked to susceptibility in some studies [34].

3.1. Humans

In humans, the codon 129 M/V polymorphism influences both prion disease susceptibility and phenotype. In sporadic CJD, all polymorphisms are susceptible to disease, but homozygosity is greatly overrepresented, despite 129MV having a prevalence as high as 51% in some unaffected populations [24,35]. In contrast, vCJD has been seen almost exclusively in people with the 129MM genotype [36] with the exception of one case, possibly two, where vCJD occurred in association with the 129MV genotype [37]. The 129 M/V polymorphism also influences the type of prion conformation that is generated. Ninety percent of 129MM patients have Type 1, which is defined by a 21 kDa fragment after proteinase K (PK) digestion, whereas 80% of patients with 129VV or 129MV develop Type 2, which has a 19 kDa fragment after digestion [3,38,39].

3.2. Elk

The 132 M/L polymorphism in elk is of great interest as it corresponds to 129 M/V polymorphism in humans and may have a similar influence on susceptibility. Some studies have found a predominance of the 132M allele in infected elk, suggesting a predisposition of 132MM towards CWD development [40,41]. A small study that inoculated elk calves harboring all three genotypes (2 132MM, 2 132ML, 4 132LL) with 132MM CWD-infected elk brain inoculum found a dose-dependent effect of the M allele, with 132MM elk developing clinical signs at 23 months post infection (mpi), 132ML at 40 mpi [42] and 132LL at 59 mpi. In the 132LL animals, a novel PrPD was detected, one with a more C-terminal proteinase K cleavage site (residues 98–133 compared to 78 or 82) [43]. This suggests that 132L may confer protection by prolonging the disease, at least when exposed to a mismatched inoculum containing 132MM CWD. The importance of strains used for these studies cannot be overstated. The premise of the species barrier relies on mismatched PrP sequence, so mismatched strain–host PrP would be predicted to have longer incubation periods. Further to this point, a larger study of 124 uninfected and 47 infected elk from Colorado found no effect of the 132M allele on susceptibility to CWD [44].

3.3. Mule Deer

Mule deer have two dimorphic polymorphisms, 225 S/F and 20 D/G, that have been associated with CWD susceptibility [34]. A study of 1482 free ranging mule deer in Colorado and Wyoming, including 289 CWD-infected animals, found that mule deer with the 225SS allele were 30 times more likely to have CWD compared to those with 225SF [45]. This suggests a potentially protective effect of the 225F allele, analogous to the 132L allele in elk. Interestingly, there was no influence of the 20 D/G polymorphism in these animals [45], whereas in an identical but smaller study of 249 mule deer in Canada, the presence of the 20G allele was associated with twice the rate of CWD infection compared to 20DD [46]. Whether these differences reflect sample size or exposure to different CWD strains is unclear. It is also intriguing to consider how changes in codon 20 could contribute to altered susceptibility, given that it lies outside the sequence included in the mature form of PrP.

3.4. White-Tailed Deer

In white-tailed deer, the PRNP alleles Q95/G96 (wild type), Q95/S96 (referred to as S96), H95/G96 (referred to as H95), and H95/S96 are associated with variable CWD susceptibility [47,48]. When white-tailed deer containing these polymorphisms were infected with wild-type hunter-harvested deer from Wisconsin, infection was fastest in the wild-type Q95/G96 deer at 693 days post-infection (dpi), followed by 956 dpi in S96 deer, 1508 dpi in H95 deer, and 1596 dpi in H95/S96 deer, suggesting that S96 and H95 alleles in the host led to longer incubation time and partial protection [49]. Inoculation of PrPCWD from 96SS white-tailed deer into transgenic mice harboring alleles 96GG, 96GS and 96SS resulted in disease in 96GG mice, delayed disease in 96GS mice, and no disease in the 96SS mice. This further supported the hypothesis that the S allele is protective or can slow down the disease [50]. One other polymorphism has been recently discovered, 116A/G, but its role in CWD susceptibility has not yet been studied in detail [51].

3.5. Moose

Two polymorphisms, 109 K/Q and 209 M/I, have been identified in moose PRNP. Both 109K/209M and 109K/209I are found in North America whereas 109Q/209M and 109K/209M alleles are found in European moose [52]. However, association of PRNP polymorphism with CWD susceptibility has not yet been demonstrated experimentally or naturally in moose, because of low numbers [14,53,54].

3.6. Reindeer

In reindeer, there are polymorphisms at several sites: 2 V/M, 129 G/S, 138 S/N, 169 V/M, 176 N/D and 225 S/Y. Notably, 176DD is seen only in reindeer [52]. The heterozygous 138SN is associated with delay or resistance to CWD infection during oral transmission [55], but intracranial inoculation of 138SN reindeer does result in CWD infection [56].

4. The Role of Strains and Adaptation

In addition to the primary sequences of PrP, transmission is also dependent on strain [33]. Strains are defined by their abilities to cause distinct clinical signs, incubation periods, pathological profiles and/or PrP biochemical characteristics that are retained on passage [24,33,57]. They are thought to arise from different conformations of misfolded PrP, which may or may not have the same underlying PrP sequence. The ability of strains to propagate and cause disease may vary within the same host and a subset of strains may cross the species barrier and cause disease by adaptation after passage in different host [24]. For example, the inoculation of sheep-passaged bovine prions into Tg mice that express cervid PrP caused prion infection, whereas directly infecting these mice with bovine prions did not [58]. Such species adaptation through passage is of high relevance to CWD because PrPCWD exists in the environment, available for other host infections.

There is evidence for different strains of CWD, often emerging through passage in transgenic mice, but the strains themselves are not yet well characterized and are influenced heavily by PrP polymorphisms. Whether all the strains detected across the cervids are different is not clear because there are few ways to discriminate subtle differences in strains.

4.1. Elk

When Tg(CerPrP)1536+/− mice that express cervid PrP were inoculated with elk PrPCWD, two strains, CWD 1 and CWD 2, were produced, whereas inoculation with mule deer PrPCWD produced strain mixtures [59]. Tg12 mice that express elk 132M PrP were inoculated with elk PrPCWD of genotype 132MM, 132ML or 132LL and also produced two different PrPD profiles, dependent on the polymorphism of the inoculum [60].

4.2. Deer

Oral inoculation of Wisc-1 CWD into white-tail deer harboring wt/wt, wt/S96, H95/wt, or H95/S96 PrP led to the detection of Wisc-1 strain in wt/wt and wt/S96 but the presence of new strain H95+ in H95/wt and H95/S96 [47,48].

4.3. Moose

Two types of naturally occurring CWD have been found in moose: 209MM in Norway and 209II in Canada, each with distinct PrPD profiles and neuropathology [54].

Given the growing evidence for strains and strain mixtures within naturally infected cervids, and the implications this has for transmission, more in vitro and in vivo studies of different CWD isolates and different PrP polymorphisms are necessary to fully assess the risks of CWD adaptation and potential to cross species barriers.

5. Crossing the Species Barrier

To date, there are no reports of prion disease transmission to livestock or humans in CWD endemic areas, either because there is a strong species barrier to non-cervid species [61], or not enough time has passed for sufficient dose exposure or incubation period. Epidemiological data, as well as in vivo and in vitro experiments, have been used to assess the likelihood of CWD crossing the species barrier into humans, with mixed results.

5.1. In Vitro Studies

Research groups have used protein misfolding cyclic amplification (PMCA) or real-time quaking-induced conversion (RT-QuIC) to test whether CWD prions can propagate in the presence of PrPC from other species, including human. In a PMCA study of 12 non-cervid species, ferrets, voles, hamsters and field mice supported the conversion whereas prairie dog, Tg huPrP mice, coyote, cat, macaques and wild-type mice failed to support amplification [22,62]. Analysis of PrP sequences in the β2–α2 (166–175) loop suggested that species containing asparagine at position 170 supported conversion, in addition to the ferret which has serine at position 170 but still was able to amplify CWD prions. It is interesting to note that, except for ferret, all other non-cervid species possessed phenylalanine at residue 175, whereas ferret has leucine at this site, which may induce stability in the loop and thereby support conversion [22,62].

Other studies have successfully generated protease-resistant human PrP aggregates after exposure to PrPCWD. Human brain homogenates, transgenic mice, and 239F cells expressing human PrP with the 129M or 129V polymorphism were able to support PrPCWD amplification in PMCA, with preferential conversion of PrP harboring the 129M allele. Interestingly, the number of amplification cycles required differed depending on the strain of CWD used; mule deer PrPCWD required multiple rounds, whereas elk and white-tailed deer PrPCWD required only one [61,63,64]. Whether this represents a difference in species barrier is unclear. RT-QuIC has also been used to demonstrate the ability of PrPCWD to seed the aggregation of human PrP [65]. 5.2. In Vivo Experiments

Attempts to transmit CWD strains into Tg mice expressing human PrP with different polymorphisms 129MM, MV and VV have failed to induce any disease [66,67]. Intracerebral and oral inoculation of cervid prions into squirrel monkeys did result in PrPD deposition and spongiform degeneration [68,69], but intracerebral and oral inoculation into macaques, which are more closely related to humans, failed to cause any signs of disease [69]. When interpreting transmission studies, it is important to consider the species, method and route of infection used. For example, intracerebral inoculation of cattle and sheep with PrPCWD from mule deer resulted in disease within 3–5 years for cattle and 3 years for sheep [70,71]; however, oral inoculation of mule deer PrPCWD into 12 calves failed to cause any disease [72]. Given that oral exposure is the most probable method of real-world transmission to humans and other species, the fact that recurrent sonication in vitro or intracerebral inoculation in vivo can induce aggregation or disease does not necessarily predict the future CWD landscape.

5.3. Human Data

There are no documented case reports of CWD transmission to humans. The largest exposure occurred at a sportsman feast in Oneida county, NY, where 200 people were unknowingly exposed to CWD-infected venison meat. No cases of CJD were reported after 6 years of follow-up with 81 participants [73]. Other reports have tried to link cases of CJD with venison exposure, but proof of exposure to CWD is lacking in most cases. From 1997 to 1990, there were reports on the deaths of three unusually young people diagnosed with CJD who had a history of regular consumption of deer or elk meat [74]. Subsequently there were reports on the diagnosis of CJD in hunters who participated in wild game feast in Wisconsin (CDC 2003 report), detection of CJD in Colorado in a 52-year-old woman who had a CWD laboratory exposure, and a 25-year-old man with CJD who had consumed venison meat in a CWD endemic area [75]. In all the above studies, patients had PRNP genotypes, PrPD biochemical characteristics and pathologies suggestive of sporadic CJD. A subsequent study from Colorado demonstrated no statistically significant increase in CJD cases within CWD-endemic areas [76].

6. Detecting CWD in Humans; the Role of Surveillance and Strain Typing

If transmission of CWD to humans occurs, it will most likely be through the oral route and occur in a CWD-endemic area where cervids are hunted and/or consumed [19]. We predict that it would induce a neurological phenotype, but whether it would be clinically or biochemically distinct from sCJD is impossible to know. In a PMCA study where elkPrPCWD generated PrPres from human brain homogenate harboring 129M PrPC, the resultant huPrPres was identical to sCJDMM1 [77]. Hopefully, from a surveillance perspective, any CWD presenting in humans will have a unique clinical presentation and/or a PrPD biochemical profile that matches that of a known CWD strain, analogous to the PrPBSE fingerprint seen in vCJD. Of course, to identify the emergence of a new PrPD profile, we require strain typing on all CWD and CJD strains that are currently occurring. If a unique fingerprint or strain shift does not occur, we will still have surveillance to detect any increased incidence of CJD cases among patients consuming venison in CWD-endemic areas, recognizing that such exposures may take decades or more to declare themselves.

In ongoing surveillance in Canada, where cases of CJD are identified and flagged for a history of venison consumption, we have not yet seen a change in CJD strain profiles in CWD-affected provinces. Several parameters have been examined as part of this strain typing and comparison, including clinical presentations, MRI findings, pathological profiles and pattern of PrPD resistance to PK (Figure 1). Additionally, analysis of total PrPD by two-dimensional gel electrophoresis, which detects differences in the extent of glycosylation and other posttranslational modifications that cannot be detected by one-dimensional blotting, also has not revealed any differences in CJD strain patterns between non-exposed and venison-exposed cases (Figure 2). This is perhaps not surprising, given that human exposure to CWD so far has been low, and incubation periods may be very long. However, this analysis provides the most in-depth profile of the current human CJD strain landscape.

Viruses 12 01454 g001 550Figure 1. Immunoblot profiles of PK-resistant PrP from brains of Creutzfeldt–Jakob disease (CJD) patients, with or without exposure to venison, compared with chronic wasting disease (CWD) strains. (A,B) Typing studies for non-venison (A) and venison (B) exposed CJD cases were carried out as described previously [78], with 10% brain homogenates in lysis buffer (LB100) (100 mM Tris HCl pH 7.0, 100 mM NaCl, 10 mM EDTA, 0.5% Nonidet-P 40, 0.5% sodium deoxycholate) digested with 70 U/mL PK for 1 h at 37 °C. Different sample volumes were loaded or blots from different runs were included to obtain a similar PrP signal intensities for comparison of banding profiles. Type 1 (21 kDa) is indicated by a solid arrow, Type 2 (19 kDa) by dashed arrow, and 20 kDa from variably protease sensitive prionopathy (VPSPr) indicated with *. Primary Ab: 3F4. (C) Typing study of CWD strains, with 10% homogenates in LB100 pH 8.0 digested with 30 U/mL PK. Wisc-1 was propagated in Tg33 mice and H95/S96 was first passaged in Tg60 mice. BH from deer and elk harboring different polymorphisms was also analyzed. Primary Ab: Sha31 Viruses 12 01454 g002 550Figure 2. Representative images of PrPSc 2D-electrophoresis are shown. PrPSc was precipitated from brain homogenate using sarkosyl and NaPTA. Extracted proteins were separated in the first dimension on Ready-Strip IPC strips (Bio-Rad) and a pH gradient of 3–10. Following equilibration in SDS and reducing/alkylating agents, the second dimension of the gel was performed on Criterion Tris-HCL polyacrylamide precast gels (8–16%) prior to Western blotting. PrPSc was detected using the 3F4 antibody and an HRP secondary. Four strips of spots were identified at different molecular weights: 32 kDa (red), 29 kDa (green), 23k Da (blue) and 13/14 kDa (purple). (A) Non-venison exposed CJD subject; (B–D) venison exposed CJD subjects. We also need data on the growing CWD strain landscape. Currently, immunohistochemistry, enzyme immunoassay, Western blotting, RT-QuIC and PMCA are the methods available for detection of PrPCWD [61]. Unfortunately, most strain information is obtained from immunohistochemistry and Western blotting and levels of PrPCWD may be too low to detect by these methods unless animals are at a late stage of the disease. PMCA and RT-QuIC can detect low levels of PrPCWD in the preclinical phase or subclinical phase, but have traditionally been used for detection, not strain typing. We have recently found that the kinetics of RT-QuIC may have value as a CJD surveillance tool, as we detected remarkably consistent kinetic seeding profiles for distinct CJD types, allowing for the identification of a number of outliers (Figure 3). Interestingly, the outliers identified through RT-QuIC correlated with rare subtypes identified by Western blot analysis and pathology. These findings suggest that RT-QuIC may be useful in differentiating some human prion strains.

Viruses 12 01454 g003 550Figure 3. Real-time quaking-induced conversion (RT-QuIC) was performed on 10−4 dilutions of brain homogenate from 25 cases of sCJD using 3 different substrates: full-length mouse, hamster and bank vole. Conversion rate was measured by comparing the time at which fluorescence in a given reaction exceeds a pre-defined threshold, i.e., the lag phase. Lag phases for each case were normalized to a 263 K hamster brain homogenate run concurrently as a standard to allow direct comparison between each run. These values were plotted on a scatter plot where the axes represent the normalized lag phase for each substrate. (A) Cases were colored according to the biochemical subtypes: Type 1, shown in grey, and Type 2, shown in brown. Two cases where a mixture of Type 1 and Type 2 were identified are shown in yellow. Cases shown in green are two cases of variably protease sensitive prionopathy (VPSPr). A Type 1 case with a biochemically distinct denaturation profile is shown in green and two others that do not exhibit typical glycoform patterns by Western blot shown in pink and purple. (B) Data were colored to reflect RT-QuIC seeding from brains of CJD patients, with or without exposure to venison, shown as blue or red, respectively.

As we gain more insight into CWD strains and their properties, we need to continue monitoring and strain-typing human cases, looking for evidence of new PrP fingerprints. We must also watch for increasing CJD cases in CWD-endemic areas. On one hand, evidence supports a strong species barrier to human transmission of CWD. On the other hand, we are identifying a variety of CWD strains, some of which can convert human PrP under experimental conditions. Humans will also co-exist with PrPCWD in the environment for decades to come. Will these factors be sufficient to allow strain adaptation and a crossing of the species barrier? Only time will tell.

Author Contributions

S.K.N. and V.L.S. wrote the manuscript and provided data for Figure 1; J.L.M., L.L. and S.A.B. provided data for Figure 2 and Figure 3. All authors have read and agreed to the published version of the manuscript.

Funding

This research was funded by Alberta Prion Research Institute, grant number 201700014.

Acknowledgments

We thank Gerard Jansen with the CJD Surveillance System of Canada for providing the CJD samples, and the lab of Deb McKenzie for providing CWD samples used in Figure 1.

Conflicts of Interest

The authors declare no conflict of interest.

References

https://www.mdpi.com/1999-4915/12/12/1454/htm

> 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).***

http://www.tandfonline.com/doi/full/10.4161/pri.28124?src=recsys

http://www.tandfonline.com/doi/pdf/10.4161/pri.28124?needAccess=true

https://wwwnc.cdc.gov/eid/article/20/1/13-0858_article

Chronic Wasting Disease CWD TSE Prion aka mad deer disease zoonosis

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.

http://grantome.com/grant/NIH/R01-NS088604-04

ZOONOTIC CHRONIC WASTING DISEASE CWD TSE PRION UPDATE

Prion 2017 Conference

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

PRION 2018 CONFERENCE

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

Hermann M. Schatzl, Samia Hannaoui, Yo-Ching Cheng, Sabine Gilch (Calgary Prion Research Unit, University of Calgary, Calgary, Canada) Michael Beekes (RKI Berlin), Walter Schulz-Schaeffer (University of Homburg/Saar, Germany), Christiane Stahl-Hennig (German Primate Center) & Stefanie Czub (CFIA Lethbridge).

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 detected in spinal cord and brain of some 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 pre-clinical 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..

***> 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. <***

Prion Conference 2018

READING OVER THE PRION 2018 ABSTRACT BOOK, LOOKS LIKE THEY FOUND THAT from this study ;

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..

SEEMS THAT THEY FOUND Highly endemic states had a higher rate of prion disease mortality compared to non-CWD
states.

AND ANOTHER STUDY;

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..

IN THIS STUDY, THERE WERE autopsy-proven prion cases from the National Prion Disease Pathology Surveillance Center that were diagnosed between September 2016 to March 2017,

AND

included 104 patients. SEEMS THEY FOUND THAT The most common sCJD subtype was MV1-2 (30%), followed by MM1-2 (20%),

AND

THAT The Majority of cases were male (60%), AND half of them had exposure to wild game.

snip…

see more on Prion 2017 Macaque study from Prion 2017 Conference and other updated science on cwd tse prion zoonosis below…terry

Prion 2018 Conference

http://transmissiblespongiformencephalopathy.blogspot.com/2018/05/prion-2018-may-22-25-2018-santiago-de.html

http://prionconference.blogspot.com/2018/

https://prionprp.blogspot.com/2018/12/adrd-summit-rfi-singeltary-comment.html

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.

https://efsa.onlinelibrary.wiley.com/doi/full/10.2903/j.efsa.2018.5132

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

https://www.alliedacademies.org/conference-abstracts-files/zoonotic-potential-of-chronic-wasting-disease-prions-from.pdf

https://prionconference.blogspot.com/2018/02/prion-round-table-conference-2018-may.html

http://prionconference.blogspot.com/2018/02/prion-round-table-conference-2018-may.html

http://prionconference.blogspot.com/

Fri, Nov 13, 2020 10:50 am

Subject: CWD TSE PRION, SCRAPIE, BSE, AND PORCINE, PIGS, WILD BOAR, ZOONOTIC ZOONOSIS RISK FACTORS AND POTENTIALS

CJD FOUNDATION VIRTUAL CONFERENCE CJD Foundation Research Grant Recipient Reports Panel 2 Nov 3, 2020

zoonotic potential of PMCA-adapted CWD PrP 96SS inoculum

https://youtu.be/VfazuR7cjMc?t=1992

4 different CWD strains, and these 4 strains have different potential to induce any folding of the human prion protein.

https://youtu.be/VfazuR7cjMc?t=2019

***> PIGS, WILD BOAR, CWD <***

***> POPULATIONS OF WILD BOARS IN THE UNITED STATES INCREASING SUPSTANTUALLY AND IN MANY AREAS WE CAN SEE A HIGH DENSITY OF WILD BOARS AND HIGH INCIDENT OF CHRONIC WASTING DISEASE

HYPOTHOSIS AND SPECIFIC AIMS

HYPOTHOSIS

BSE, SCRAPIE, AND CWD, EXPOSED DOMESTIC PIGS ACCUMULATE DIFFERENT QUANTITIES AND STRAINS OF PRIONS IN PERIPHERAL TISSUES, EACH ONE OF THEM WITH PARTICULAR ZOONOTIC POTENTIALS

https://youtu.be/VfazuR7cjMc

Final Report – CJD Foundation Grant Program A.

Project Title: Systematic evaluation of the zoonotic potential of different CWD isolates. Principal Investigator: Rodrigo Morales, PhD.

https://cjdfoundation.org/sites/default/files/grant-downloads/Final%20Report%20-%20CJD%20Foundation%20-%20Morales.pdf

Systematic evaluation of the zoonotic potential of different CWD isolates. Rodrigo Morales, PhD Assistant Professor Protein Misfolding Disorders lab Mitchell Center for Alzheimer’s disease and Related Brain Disorders Department of Neurology University of Texas Health Science Center at Houston Washington DC. July 14th, 2018

Conclusions and Future Directions • We have developed a highly sensitive and specific CWD-PMCA platform to be used as a diagnostic tool. • Current PMCA set up allow us to mimic relevant prion inter-species transmission events. • Polymorphic changes at position 96 of the prion protein apparently alter strain properties and, consequently, the zoonotic potential of CWD isolates. • Inter-species and inter-polymorphic PrPC → PrPSc conversions further increase the spectrum of CWD isolates possibly present in nature. • CWD prions generated in 96SS PrPC substrate apparently have greater inter-species transmission potentials. • Future experiments will explore the zoonotic potential of CWD prions along different adaptation scenarios, including inter-species and inter-polymorphic.

https://cjdfoundation.org/files/Conf2018/Rodrigo%20Morales%202018.pdf

https://www.youtube.com/watch?v=CzQKemJRBlE&list=PLGXRDfDPg57yTYvn6tifH13NrSiLjv1d7&index=7&t=0s

Research Project: TRANSMISSION, DIFFERENTIATION, AND PATHOBIOLOGY OF TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES Location: Virus and Prion Research

Title: Disease-associated prion protein detected in lymphoid tissues from pigs challenged with the agent of chronic wasting disease

Author item MOORE, SARAH - Orise Fellow item Kunkle, Robert item KONDRU, NAVEEN - Iowa State University item MANNE, SIREESHA - Iowa State University item SMITH, JODI - Iowa State University item KANTHASAMY, ANUMANTHA - Iowa State University item WEST GREENLEE, M - Iowa State University item Greenlee, Justin Submitted to: Prion Publication Type: Abstract Only Publication Acceptance Date: 3/15/2017 Publication Date: N/A Citation: N/A Interpretive Summary:

Technical Abstract: Aims: Chronic wasting disease (CWD) is a naturally-occurring, fatal neurodegenerative disease of cervids. We previously demonstrated that disease-associated prion protein (PrPSc) can be detected in the brain and retina from pigs challenged intracranially or orally with the CWD agent. In that study, neurological signs consistent with prion disease were observed only in one pig: an intracranially challenged pig that was euthanized at 64 months post-challenge. The purpose of this study was to use an antigen-capture immunoassay (EIA) and real-time quaking-induced conversion (QuIC) to determine whether PrPSc is present in lymphoid tissues from pigs challenged with the CWD agent.

Methods: At two months of age, crossbred pigs were challenged by the intracranial route (n=20), oral route (n=19), or were left unchallenged (n=9). At approximately 6 months of age, the time at which commercial pigs reach market weight, half of the pigs in each group were culled (<6 month challenge groups). The remaining pigs (>6 month challenge groups) were allowed to incubate for up to 73 months post challenge (mpc). The retropharyngeal lymph node (RPLN) was screened for the presence of PrPSc by EIA and immunohistochemistry (IHC). The RPLN, palatine tonsil, and mesenteric lymph node (MLN) from 6-7 pigs per challenge group were also tested using EIA and QuIC.

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.

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

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

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

Title: The agent of chronic wasting disease from pigs is infectious in transgenic mice expressing human PRNP

Author item MOORE, S - Orise Fellow item Kokemuller, Robyn item WEST-GREENLEE, M - Iowa State University item BALKEMA-BUSCHMANN, ANNE - Friedrich-Loeffler-institut item GROSCHUP, MARTIN - Friedrich-Loeffler-institut item Greenlee, Justin Submitted to: Prion Publication Type: Abstract Only Publication Acceptance Date: 5/10/2018 Publication Date: 5/22/2018 Citation: Moore, S.J., Kokemuller, R.D., West-Greenlee, M.H., Balkema-Buschmann, A., Groschup, M.H., Greenlee, J.J. 2018. The agent of chronic wasting disease from pigs is infectious in transgenic mice expressing human PRNP. Prion 2018, Santiago de Compostela, Spain, May 22-25, 2018. Paper No. WA15, page 44.

Interpretive Summary:

Technical Abstract: We have previously shown that the chronic wasting disease (CWD) agent from white-tailed deer can be transmitted to domestic pigs via intracranial or oral inoculation although with low attack rates and restricted PrPSc accumulation. The objective of this study was to assess the potential for cross-species transmission of pig-passaged CWD using bioassay in transgenic mice. Transgenic mice expressing human (Tg40), bovine (TgBovXV) or porcine (Tg002) PRNP were inoculated intracranially with 1% brain homogenate from a pig that had been intracranially inoculated with a pool of CWD from white-tailed deer. This pig developed neurological clinical signs, was euthanized at 64 months post-inoculation, and PrPSc was detected in the brain. Mice were monitored daily for clinical signs of disease until the end of the study. Mice were considered positive if PrPSc was detected in the brain using an enzyme immunoassay (EIA). In transgenic mice expressing porcine prion protein the average incubation period was 167 days post-inoculation (dpi) and 3/27 mice were EIA positive (attack rate = 11%). All 3 mice were found dead and clinical signs were not noted prior to death. One transgenic mouse expressing bovine prion protein was euthanized due to excessive scratching at 617 dpi and 2 mice culled at the end of the study at 700 dpi were EIA positive resulting in an overall attack rate of 3/16 (19%). None of the transgenic mice expressing human prion protein that died or were euthanized up to 769 dpi were EIA positive and at study end point at 800 dpi 2 mice had positive EIA results (overall attack rate = 2/20 = 10%). The EIA optical density (OD) readings for all positive mice were at the lower end of the reference range (positive mice range, OD = 0.266-0.438; test positive reference range, OD = 0.250-4.000). To the authors’ knowledge, cervid-derived CWD isolates have not been successfully transmitted to transgenic mice expressing human prion protein. The successful transmission of pig-passaged CWD to Tg40 mice reported here suggests that passage of the CWD agent through pigs results in a change of the transmission characteristics which reduces the transmission barrier of Tg40 mice to the CWD agent. If this biological behavior is recapitulated in the original host species, passage of the CWD agent through pigs could potentially lead to increased pathogenicity of the CWD agent in humans.

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

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.

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

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

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

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

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

1Virus and Prion Research Unit, National Animal Disease Center, USDA, Agricultural Research Service, Ames, Iowa, United States of America 2Oak Ridge Institute for Science and Education, Oak Ridge, Tennessee, United States of America 3Department of Biomedical Sciences, Iowa State University College of Veterinary Medicine, Ames, Iowa, United States of America

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.

IMPORTANCE We challenged domestic swine with the chronic wasting disease agent by inoculation directly into the brain (intracranially) or by oral gavage (orally). Disease-associated prion protein (PrPSc) was detected in brain and lymphoid tissues from intracranially and orally inoculated pigs as early as 8 months of age (6 months post-inoculation). Only one pig developed clinical neurologic signs suggestive of prion disease. The amount of PrPSc in the brains and lymphoid tissues of positive pigs was small, especially in orally inoculated pigs. Regardless, positive results in orally inoculated pigs suggest that it may be possible for swine to serve as a reservoir for prion disease under natural conditions.

FOOTNOTES

↵*Corresponding author: Email: justin.greenlee@ars.usda.gov This is a work of the U.S. Government and is not subject to copyright protection in the United States. Foreign copyrights may apply.

http://jvi.asm.org/content/early/2017/07/06/JVI.00926-17.abstract

----Original Message-----

From: Terry Singeltary

To: Tracy.A.Nichols

Sent: Fri, Mar 30, 2018 12:51 pm

Subject: Docket No. APHIS-2018-0011 Chronic Wasting Disease Herd Certification Program Standards Singeltary Submission March 30, 2018

Docket No. APHIS-2018-0011 Chronic Wasting Disease Herd Certification Program Standards Singeltary Submission March 30, 2018

Greetings APHIS, USDA, Dr. Tracy Nichols, et al,

I wish to kindly submit my comments on the Docket No. APHIS-2018-0011 Chronic Wasting Disease Herd Certification Program Standards please. i have submitted online and sent a hard copy to Dr. Nichols via email. i know that my concern may not be the same concern as others, but ramifications from cwd tse prion can be long lasting, and science is still emerging. however, the science today warrants immediate and further actions be taken. my comments, with reference materials, are as follows, and will be formatted in such a way, i will address issues by numbers 1-10, and under each one of my comments by each number, i will reference my comments with science to back up what i am stating/asking...thank you kindly, terry

snip...see full text;

WEDNESDAY, NOVEMBER 4, 2020

CWD TSE PRION, SCRAPIE, BSE, AND PORCINE, PIGS, WILD BOAR, ZOONOTIC ZOONOSIS RISK FACTORS AND POTENTIALS

https://transmissiblespongiformencephalopathy.blogspot.com/2020/11/cwd-tse-prion-scrapie-bse-and-porcine.html

2.3.2. New evidence on the zoonotic potential of atypical BSE and atypical scrapie prion strains

PLEASE NOTE;

2.3.2. New evidence on the zoonotic potential of atypical BSE and atypical scrapie prion strains

Olivier Andreoletti, INRA Research Director, Institut National de la Recherche Agronomique (INRA) – École Nationale Vétérinaire de Toulouse (ENVT), invited speaker, presented the results of two recently published scientific articles of interest, of which he is co-author: ‘Radical Change in Zoonotic Abilities of Atypical BSE Prion Strains as Evidenced by Crossing of Sheep Species Barrier in Transgenic Mice’ (MarinMoreno et al., 2020) and ‘The emergence of classical BSE from atypical/Nor98 scrapie’ (Huor et al., 2019).

In the first experimental study, H-type and L-type BSE were inoculated into transgenic mice expressing all three genotypes of the human PRNP at codon 129 and into adapted into ARQ and VRQ transgenic sheep mice. The results showed the alterations of the capacities to cross the human barrier species (mouse model) and emergence of sporadic CJD agents in Hu PrP expressing mice: type 2 sCJD in homozygous TgVal129 VRQ-passaged L-BSE, and type 1 sCJD in homozygous TgVal 129 and TgMet129 VRQ-passaged H-BSE.

SUNDAY, OCTOBER 11, 2020

Bovine adapted transmissible mink encephalopathy is similar to L-BSE after passage through sheep with the VRQ/VRQ genotype but not VRQ/ARQ

https://transmissible-mink-encephalopathy.blogspot.com/2020/10/bovine-adapted-transmissible-mink.html

THURSDAY, SEPTEMBER 24, 2020

The emergence of classical BSE from atypical/ Nor98 scrapie

https://nor-98.blogspot.com/2020/09/the-emergence-of-classical-bse-from.html

WEDNESDAY, OCTOBER 28, 2020

EFSA Annual report of the Scientific Network on BSE-TSE 2020 Singeltary Submission

https://efsaopinionbseanimalprotein.blogspot.com/2020/10/efsa-annual-report-of-scientific.html

----Original Message-----

From: Terry Singeltary

To: Tracy.A.Nichols

Sent: Fri, Mar 30, 2018 12:51 pm

Subject: Docket No. APHIS-2018-0011 Chronic Wasting Disease Herd Certification Program Standards Singeltary Submission March 30, 2018

Docket No. APHIS-2018-0011 Chronic Wasting Disease Herd Certification Program Standards Singeltary Submission March 30, 2018

Greetings APHIS, USDA, Dr. Tracy Nichols, et al,

snip...see full text;

WEDNESDAY, NOVEMBER 4, 2020

CWD TSE PRION, SCRAPIE, BSE, AND PORCINE, PIGS, WILD BOAR, ZOONOTIC ZOONOSIS RISK FACTORS AND POTENTIALS

https://transmissiblespongiformencephalopathy.blogspot.com/2020/11/cwd-tse-prion-scrapie-bse-and-porcine.html

THE FEAST

Exposure Risk of Chronic Wasting Disease in Humans

by Satish K. Nemani 1,2,Jennifer L. Myskiw 3,4,Lise Lamoureux 3,Stephanie A. Booth 3,4 andValerie L. Sim 1,2,*OrcID

1 Centre for Prions and Protein Folding Diseases, Edmonton, AB T6G 2R3, Canada

2 Department of Medicine, Division of Neurology, University of Alberta, Edmonton, AB T6G 2R3, Canada

3 Zoonotic Diseases and Special Pathogens, Public Health Agency of Canada, National Microbiology Laboratory, Winnipeg, MB R3E 3R2, Canada

4 Department of Medical Microbiology and Infectious Diseases, Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3E 3R2, Canada

* Author to whom correspondence should be addressed. Academic Editor: Byron Caughey Viruses 2020, 12(12), 1454; https://doi.org/10.3390/v12121454 Received: 1 December 2020 / Revised: 14 December 2020 / Accepted: 15 December 2020 / Published: 17 December 2020 (This article belongs to the Special Issue The Future of the Chronic Wasting Disease Epizootic) View Full-Text Download PDF Browse Figures Review Reports Cite This Paper

Abstract

View Full-Text

Keywords: chronic wasting disease (CWD); zoonotic potential; bovine spongiform encephalopathy (BSE); variant Creutzfeldt–Jakob disease (vCJD); sporadic CJD; CWD prions (PrPCWD); proteinase K resistant prion protein (PK-resPrP); strains; PRNP polymorphism; 129M/V polymorphism

snip...

5.3. Human Data There are no documented case reports of CWD transmission to humans.

The largest exposure occurred at a sportsman feast in Oneida county, NY, where 200 people were unknowingly exposed to CWD-infected venison meat. No cases of CJD were reported after 6 years of follow-up with 81 participants [73]. Six-year follow-up of a point-source exposure to CWD contaminated venison in an Upstate New York community: Risk behaviours and health outcomes 2005–2011. Public Health 2014, 128, 860–868.

Other reports have tried to link cases of CJD with venison exposure, but proof of exposure to CWD is lacking in most cases. From 1997 to 1990, there were reports on the deaths of three unusually young people diagnosed with CJD who had a history of regular consumption of deer or elk meat [74].

Subsequently there were reports on the diagnosis of CJD in hunters who participated in wild game feast in Wisconsin (CDC 2003 report), detection of CJD in Colorado in a 52-year-old woman who had a CWD laboratory exposure, and a 25-year-old man with CJD who had consumed venison meat in a CWD endemic area [75]. In all the above studies, patients had PRNP genotypes, PrPD biochemical characteristics and pathologies suggestive of sporadic CJD. A subsequent study from Colorado demonstrated no statistically significant increase in CJD cases within CWD-endemic areas [76].

snip...see full text;

https://www.mdpi.com/1999-4915/12/12/1454

A FURTHER REVEIW OF THIS SHOWS THAT ACTUALLY THERE WERE MEN THAT PARTICIPATED IN THIS FEAST THAT DID DIE OF A TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY TSE PRION DISEASE, 3 MEN THAT WERE REPORTED, YOU CAN SEE THIS HERE;

Fatal Degenerative Neurologic Illnesses in Men Who Participated in Wild Game Feasts --- Wisconsin, 2002

Creutzfeldt-Jakob disease (CJD) is a fatal neurologic disorder in humans. CJD is one of a group of conditions known as transmissible spongiform encephalopathies (TSEs), or prion diseases, that are believed to be caused by abnormally configured, host-encoded prion proteins that accumulate in the central nervous tissue

(1). CJD has an annual incidence of approximately 1 case per million population in the United States (1) and occurs in three forms: sporadic, genetically determined, and acquired by infection. In the latter form, the incubation period is measured typically in years. Recent evidence that prion infection can cross the species barrier between humans and cattle has raised increasing public health concerns about the possible transmission to humans of a TSE among deer and elk known as chronic wasting disease (CWD)

(2). During 1993--1999, three men who participated in wild game feasts in northern Wisconsin died of degenerative neurologic illnesses. This report documents the investigation of these deaths, which was initiated in August 2002 and which confirmed the death of only one person from CJD. Although no association between CWD and CJD was found, continued surveillance of both diseases remains important to assess the possible risk for CWD transmission to humans.

Case Reports

Case 1. In December 1992, a Wisconsin man aged 66 years with a history of seizures since 1969 sought treatment for recurring seizures, increasing forgetfulness, and worsening hand tremors. Electroencephalographic (EEG) examination demonstrated focal epileptiform activity and nonspecific diffuse abnormalities, but no specific diagnosis was made. In February 1993, he was hospitalized for increasing confusion, ataxia, and movement tremors of his extremities. A magnetic resonance image (MRI) demonstrated mild, nonspecific enhancement along the inferior parasagittal occipital lobe. A repeat EEG showed bifrontal intermittent, short-interval, periodic sharp waves, suggesting a progressive encephalopathy; a diagnosis of CJD was suspected. The man died later that month; neuropathologic examination of brain tissue during autopsy indicated subacute spongiform encephalopathy, compatible with CJD.

The man was a lifelong hunter who ate venison frequently. He hunted primarily in northern Wisconsin but also at least once in Montana. He hosted wild game feasts at his cabin in northern Wisconsin from 1976 until shortly before his death. Fixed brain tissue obtained during the autopsy was sent for analysis to the National Prion Disease Pathology Surveillance Center (NPDPSC) and reexamined at the institution where the autopsy was conducted. Histopathologic examination did not substantiate the diagnosis of prion disease. In addition, 27 brain tissue sections were negative for prions by immunostaining despite positive antibody reactions against other proteins (controls), which indicated that other epitopes in the tissue samples were preserved.

Case 2. In May 1999, a Minnesota man aged 55 years with no previous history of a neurologic disease sought evaluation and treatment following a 3-month history of progressive difficulty in writing and unsteadiness of gait. A computerized tomography (CT) scan and MRI examination of his head did not indicate any abnormality. In June 1999, he was hospitalized following onset of dementia, speech abnormalities, and myoclonic jerking. An EEG indicated left-hemispheric periodic sharp waves and moderate generalized background slowing; CJD was diagnosed clinically. In July 1999, following worsening symptoms and development of right upper extremity dystonia, the patient died. Neuropathologic evaluation of brain tissue during autopsy demonstrated widespread subcortical spongiform lesions, consistent with CJD.

The man was not a hunter but had a history of eating venison. He made an estimated 12 visits to the cabin where the wild game feasts were held, but he participated in only one feast during the mid-1980s. Sections of fixed and frozen brain tissue obtained during autopsy were analyzed at NPDPSC, and prion disease was confirmed by immunohistochemical and Western blot testing. The Western blot characteristics and prion disease phenotype in this patient were consistent with the most common form of sporadic CJD, classified as M/M (M/V) 1 (3). Subsequent genetic typing confirmed the presence of methionine homozygosity (M/M) at codon 129 of the patient's prion protein gene.

Case 3. In June 1992, a Wisconsin man aged 65 years sought treatment for progressive slowing of speech, worsening memory, and personality changes. By January 1993, his speech was reduced to one-word utterances. Neurologic examination showed a flat affect, decreased reflexes, and apraxia. A CT head scan showed mild atrophy, and an EEG was normal. Pick's disease was diagnosed. By May, he was unable to perform any daily living activities; he died in August 1993. Neuropathologic evaluation of brain tissue during autopsy showed symmetrical frontal lobe cerebral cortical atrophy and mild temporal lobe atrophy. No Pick's bodies or spongiform lesions were observed.

The man had a history of eating venison and participated regularly in wild game feasts held at the cabin owned by patient 1. He was a lifelong hunter and hunted mostly in Wisconsin but also in Wyoming and British Columbia. No game was brought to the wild game feasts from his hunting trips outside of Wisconsin. Examination of fixed brain tissue sent to NPDPSC demonstrated no lesions indicative of CJD, and immunohistochemical testing with antibody to the prion protein did not demonstrate the granular deposits seen in prion diseases.

https://www.cdc.gov/mmwr/preview/mmwrhtml/mm5207a1.htm

The man whose disease was found to be CJD was a Minnesotan who died in 1999, the report says. He had visited the Wisconsin cabin about a dozen times but had eaten wild game only once. Analysis of his brain tissue suggested that his disease was the most common form of sporadic CJD, "without apparent unusual neruopathologic or molecular characteristics that might occur if the prion related to CWD had been responsible for the disease," the CDC said.

https://www.cidrap.umn.edu/news-perspective/2003/02/cdc-finds-no-cwd-cjd-link-wisconsin-deaths

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

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

http://www.tandfonline.com/doi/full/10.4161/pri.28124?src=recsys

http://www.tandfonline.com/doi/pdf/10.4161/pri.28124?needAccess=true

https://wwwnc.cdc.gov/eid/article/20/1/13-0858_article

Chronic Wasting Disease CWD TSE Prion aka mad deer disease zoonosis

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.

http://grantome.com/grant/NIH/R01-NS088604-04

Expanding spectrum of prion diseases

Jacob I. Ayers; Nick A. Paras; Stanley B. Prusiner

Emerg Top Life Sci (2020) 4 (2): 155–167.

https://doi.org/10.1042/ETLS20200037

Prions were initially discovered in studies of scrapie, a transmissible neurodegenerative disease (ND) of sheep and goats thought to be caused by slow viruses. Once scrapie was transmitted to rodents, it was discovered that the scrapie pathogen resisted inactivation by procedures that modify nucleic acids. Eventually, this novel pathogen proved to be a protein of 209 amino acids, which is encoded by a chromosomal gene. After the absence of a nucleic acid within the scrapie agent was established, the mechanism of infectivity posed a conundrum and eliminated a hypothetical virus. Subsequently, the infectious scrapie prion protein (PrPSc) enriched for β-sheet was found to be generated from the cellular prion protein (PrPC) that is predominantly α-helical. The post-translational process that features in nascent prion formation involves a templated conformational change in PrPC that results in an infectious copy of PrPSc. Thus, prions are proteins that adopt alternative conformations, which are self-propagating and found in organisms ranging from yeast to humans. Prions have been found in both Alzheimer's (AD) and Parkinson's (PD) diseases. Mutations in APP and α-synuclein genes have been shown to cause familial AD and PD. Recently, AD was found to be a double prion disorder: both Aβ and tau prions feature in this ND. Increasing evidence argues for α-synuclein prions as the cause of PD, multiple system atrophy, and Lewy body dementia.

Keywords:α-synuclein, amyloid beta, neurodegeneration, prion, tau proteins

Subjects:Aging, Molecular Bases of Health & Disease, Neuroscience

https://europepmc.org/article/MED/32803268?singleResult=true

S12‐4

Prion‐like propagation of pathological tau in neurodegenerative diseases

Masato Hasegawa1,2

1Department of Dementia and Higher Brain Function, Tokyo Metropolitan Institute of Medical Science; 2Department of Biological Science, Tokyo Metropolitan University

Abnormal tau pathologies are the defining features of many neurodegenerative diseases including Alzheimer's disease (AD), Pick's disease (PiD), corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP). Immunocytochemical and biochemical studies revealed widespread phosphorylated tau pathologies in these diseases, and the distributions and spread of these abnormal tau were closely correlated with clinical presentation and disease progression. In adult human brains, six tau isoforms are expressed, and they are classified to four‐repeat (4R) tau and three‐repeat (3R) tau. Tau is a highly soluble, natively unfolded protein, however, in these diseased brains, it is accumulated as filamentous inclusions in abnormally phosphorylated and partially ubiquitinated states. It is demonstrated that the conformations of the abnormal tau in these diseases are distinct between the diseases. Recent studies also have shown pathological tau proteins from brains of patients may have a prion‐like activity that can convert normal tau into an abnormal form. Therefore, we prepared synthetic tau fibrils and sarkosyl‐insoluble pellets of tauopathy brains and investigated the prion‐like seeding activities using culture cell models and injection to wild‐type mouse brains. Both synthetic tau fibrils and sarkosyl pellets of diseased brains showed prion‐like seeding activities in these cellular and animal models. The results suggest that pathological fibrillar forms of tau have prion‐like properties and propagate from cell to cell in brains of patients.

Symposium 24: S24‐1

Prion and Prion disease: An overview and challenges

Hidehiro Mizusawa1,2

1National Center of Neurology and Psychiatry; 2Tokyo Medical and Dental University

Prion diseases are devastating neurodegenerative diseases in humans such as Creutzfeldt‐Jakob disease (CJD) and many animal species including sheep, cow, deer and cat. CJD presents rapidly progressive dementia and other symptoms resulting in 100 percent death usually in months without any medicine to treat. Most CJD cases are sporadic and of unknown origin. There are also genetic forms such as genetic CJD, Gerstmann‐Straeussler‐Scheinker syndrome and Fatal Familial Insomnia and, rarely, acquired forms including iatrogenic CJD such as due to human dura mater grafts or human pituitary derived hormones. Prion diseases are caused by conversion of normal prion proteins to transmissible (infective) abnormal prion proteins (prion). Three Nobel Prizes have been awarded in this narrow field of science but mechanisms of conversion, transmission and neuronal degeneration are far from elucidation. Fortunately the outbreak of variant CJD transmitted through foods contaminated with prion of bovine spongiform encephalopathy was almost eliminated but unfortunately mechanism of infection to young adults is unknown. Chronic wasting disease of deer spreading in north America, south Korea and recently in northern Europe appears an emerging threat to us. Recent studies on A‐beta, Tau, alpha‐synuclein and others linked to Alzheimer's disease, Parkinson's disease and so on demonstrated they also share characteristics with prion proteins, notably auto‐aggregation, self‐propagation and induction of lesions in animals. These findings suggest that research and development of treatment on Prion disease would contribute greatly to overcome such neurodegenerative diseases. International cooperation all over the world is crucial in overcoming Prion diseases.

https://onlinelibrary.wiley.com/doi/10.1111/bpa.12675

Prion diseases in humans and their relevance to other neurodegenerative diseases

J Collinge 1, M S Palmer

PMID: 8401789 DOI: 10.1159/000107320

Abstract

Molecular genetics has led to considerable advances in our understanding of the transmissible spongiform encephalopathies. The identification of pathogenic mutations in the prion protein gene has enabled a molecular reclassification of the familial forms of these diseases, which may now be referred to as inherited prion diseases. Prion diseases of both humans and animals are associated with deposition of an abnormal isoform of a host-encoded protein, the prion protein (PrP). Human prion diseases have inherited, sporadic and acquired forms. A considerable body of evidence now supports the idea that the transmissible agent in these diseases may be an abnormal isoform of the prion protein. The identification of pathogenic mutations in the PrP gene has enabled the identification of cases of inherited prion disease that would not have been recognised using existing clinical and pathological diagnostic criteria. Since marked clinical and neuropathological overlap between the different neurodegenerative disorders is well recognised, PrP gene analysis is of increasing importance in differential diagnosis. Frontal lobe dementia of non-Alzheimer type and Pick's disease share a number of important clinical and pathological features with prion diseases, and could be considered as candidate prion diseases. However, we have not been able to demonstrate either PrP mutations or the presence of the disease-associated isoform of prion protein in several well-characterised families with these disorders.

https://pubmed.ncbi.nlm.nih.gov/8401789/#:~:text=Frontal%20lobe%20dementia%20of%20non,considered%20as%20candidate%20prion%20diseases.

Table 1. Protein misfolding neurodegenerative diseases Misfolded protein Human disease Familial cases

Prion protein Kuru

Creutzfeldt-Jakob disease +/

Gerstmann–Stra¨ussler– +

Scheinker disease

Fatal familial insomnia +/

b-Amyloid Alzheimer’s disease +/

BRI2 British dementia +

Danish dementia +

Tau Alzheimer’s disease

Gerstmann–Stra¨ussler– Scheinker disease

British dementia

Danish dementia

Pick’s disease +/

Progressive supranuclear palsy +/

Corticobasal degeneration +/

Argyrophilic grain disease +/

Guam Parkinsonismdementia complex

Tangle-only dementia

White matter tauopathy

with globular glial

inclusions

Frontotemporal dementia and Parkinsonism linked to chromosome 17 +

a-Synuclein Parkinson’s disease +/

Dementia with Lewy bodies +/

Multiple system atrophy

Pure autonomic failure

Lewy body dysphagia

Superoxide dismutase 1 Amyotrophic lateral sclerosis +/

TAR DNA-binding protein 43 Amyotrophic lateral sclerosis +/

Frontotemporal dementia +/ Fused in sarcoma Amyotrophic lateral sclerosis +/

Frontotemporal dementia

Huntingtin Huntington’s disease + Symbols: ‘‘+’’ indicates that the disease is inherited and caused by dominant mutations in the gene encoding the misfolded protein or multiplications of the gene, ‘‘+/–’’ indicates that the disease is inherited in some cases and caused by such mutations or multiplications and ‘‘’’ indicates that known cases of the disease are not caused by dominant mutations in the gene encoding the misfolded protein or multiplications of the gene

https://www.cell.com/trends/neurosciences/pdf/S0166-2236(10)00055-X.pdf

***> 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.

https://efsa.onlinelibrary.wiley.com/doi/full/10.2903/j.efsa.2018.5132

*** now, let’s see what the authors said about this casual link, personal communications years ago, and then the latest on the zoonotic potential from CWD to humans from the TOKYO PRION 2016 CONFERENCE.

see where it is stated NO STRONG evidence. so, does this mean there IS casual evidence ???? “Our conclusion stating that we found no strong evidence of CWD transmission to humans”

From: TSS

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

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

From: "Belay, Ermias"

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

Sent: Monday, September 30, 2002 9:22 AM

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

Dear Sir/Madam,

In the Archives of Neurology you quoted (the abstract of which was attached to your email), we did not say CWD in humans will present like variant CJD.. That assumption would be wrong. I encourage you to read the whole article and call me if you have questions or need more clarification (phone: 404-639-3091). Also, we do not claim that "no-one has ever been infected with prion disease from eating venison." Our conclusion stating that we found no strong evidence of CWD transmission to humans in the article you quoted or in any other forum is limited to the patients we investigated.

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

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

From: Sent: Sunday, September 29, 2002 10:15 AM

To: rr26k@nih.gov; rrace@niaid.nih.gov; ebb8@CDC.GOV

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

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

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 ;

http://chronic-wasting-disease.blogspot.com/2008/04/prion-disease-of-cervids-chronic.html

*** I urge everyone to watch this video closely...terry

*** you can see video here and interview with Jeff's Mom, and scientist telling you to test everything and potential risk factors for humans ***

https://histodb11.usz.ch/Images/videos/video-004/video-004.html

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

http://cdmrp.army.mil/prevfunded/nprp/NPRP_Summit_Final_Report.pdf

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

sporadic, spontaneous CJD, 85%+ of all human TSE, just 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 https://www.ncbi.nlm.nih.gov/pubmed/?term=sporadic

spontaneous = 325,650 hits https://www.ncbi.nlm.nih.gov/pubmed/?term=spontaneous

https://chronic-wasting-disease.blogspot.com/2020/12/exposure-risk-of-chronic-wasting.html

SATURDAY, FEBRUARY 23, 2019

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

https://chronic-wasting-disease.blogspot.com/2019/02/chronic-wasting-disease-cwd-tse-prion.html

TUESDAY, NOVEMBER 04, 2014

Six-year follow-up of a point-source exposure to CWD contaminated venison in an Upstate New York community: risk behaviours and health outcomes 2005–2011

Authors, though, acknowledged the study was limited in geography and sample size and so it couldn't draw a conclusion about the risk to humans. They recommended more study. Dr. Ermias Belay was the report's principal author but he said New York and Oneida County officials are following the proper course by not launching a study. "There's really nothing to monitor presently. No one's sick," Belay said, noting the disease's incubation period in deer and elk is measured in years. "

http://chronic-wasting-disease.blogspot.com/2014/11/six-year-follow-up-of-point-source.html

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....

https://web.archive.org/web/20090506002237/http://www..bseinquiry.gov.uk/files/mb/m11b/tab01.pdf

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.

http://jvi.asm.org/content/83/18/9608.full

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.

http://science.sciencemag.org/content/311/5764/1117..long

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 $$$ ***

http://www.tandfonline.com/doi/full/10.4161/pri.28124?src=recsys

http://www.tandfonline.com/doi/pdf/10.4161/pri.28124?needAccess=true

https://wwwnc.cdc.gov/eid/article/20/1/13-0858_article

*** IF CWD is not a risk factor for humans, then I guess the FDA et al recalled all this CWD tainted elk tenderloin (2009 Exotic Meats USA of San Antonio, TX) for the welfare and safety of the dead elk. ...tss

Exotic Meats USA Announces Urgent Statewide Recall of Elk Tenderloin Because It May Contain Meat Derived From An Elk Confirmed To Have Chronic Wasting Disease

Contact: Exotic Meats USA 1-800-680-4375

FOR IMMEDIATE RELEASE -- February 9, 2009 -- Exotic Meats USA of San Antonio, TX is initiating a voluntary recall of Elk Tenderloin because it may contain meat derived from an elk confirmed to have Chronic Wasting Disease (CWD). The meat with production dates of December 29, 30 and 31, 2008 was purchased from Sierra Meat Company in Reno, NV. The infected elk came from Elk Farm LLC in Pine Island, MN and was among animals slaughtered and processed at USDA facility Noah’s Ark Processors LLC.

Chronic Wasting Disease (CWD) is a fatal brain and nervous system disease found in elk and deer. The disease is caused by an abnormally shaped protein called a prion, which can damage the brain and nerves of animals in the deer family. Currently, it is believed that the prion responsible for causing CWD in deer and elk is not capable of infecting humans who eat deer or elk contaminated with the prion, but the observation of animal-to-human transmission of other prion-mediated diseases, such as bovine spongiform encephalopathy (BSE), has raised a theoretical concern regarding the transmission of CWD from deer or elk to humans. At the present time, FDA believes the risk of becoming ill from eating CWD-positive elk or deer meat is remote. However, FDA strongly advises consumers to return the product to the place of purchase, rather than disposing of it themselves, due to environmental concerns.

Exotic Meats USA purchased 1 case of Elk Tenderloins weighing 16.9 lbs. The Elk Tenderloin was sold from January 16 – 27, 2009. The Elk Tenderloins was packaged in individual vacuum packs weighing approximately 3 pounds each. A total of six packs of the Elk Tenderloins were sold to the public at the Exotic Meats USA retail store. Consumers who still have the Elk Tenderloins should return the product to Exotic Meats USA at 1003 NE Loop 410, San Antonio, TX 78209. Customers with concerns or questions about the Voluntary Elk Recall can call 1-800-680-4375. The safety of our customer has always been and always will be our number one priority.

Exotic Meats USA requests that for those customers who have products with the production dates in question, do not consume or sell them and return them to the point of purchase. Customers should return the product to the vendor. The vendor should return it to the distributor and the distributor should work with the state to decide upon how best to dispose. If the consumer is disposing of the product he/she should consult with the local state EPA office.

RSS Feed for FDA Recalls Information11 [what's this?12]

http://www.fda.gov/Safety/Recalls/ArchiveRecalls/2009/ucm128543.htm

Elk Tenderloin has been initiated by Exotic Meats USA and announced by the U.S. Food and Drug Administration (FDA) because Elk Tenderloin may have been derived from an animals confirmed to have had Chronic Wasting Disease (CWD).

https://www.yourlawyer.com/food-poisoning/recalls-food-poisoning/chronic-wasting-disease-elk-meat/

http://chronic-wasting-disease.blogspot.com/2015/09/deer-trafficking-scheme-nets-record-16.html

FRIDAY, JULY 26, 2019

Chronic Wasting Disease in Cervids: Implications for Prion Transmission to Humans and Other Animal Species

https://chronic-wasting-disease.blogspot.com/2019/07/chronic-wasting-disease-in-cervids.html

TUESDAY, JANUARY 21, 2020

***> 2004 European Commission Chronic wasting disease AND TISSUES THAT MIGHT CARRY A RISK FOR HUMAN FOOD AND ANIMAL FEED CHAINS REPORT UPDATED 2020

https://chronic-wasting-disease.blogspot.com/2020/01/2004-european-commission-chronic.html

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: <3daf5023 .4080804="" wt.net="">

Dear Terry,

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

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

Steve Dealler ===============

https://caninespongiformencephalopathy.blogspot.com/2010/03/canine-spongiform-encephalopathy-aka.html

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

https://bseinquiry.blogspot.com/2019/02/mad-dogs-and-englishmen-bse-scrapie-cwd.html

***> 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) <***

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

MONDAY, DECEMBER 14, 2020

Experimental oral transmission of chronic wasting disease to sika deer (Cervus nippon)

https://chronic-wasting-disease.blogspot.com/2020/12/experimental-oral-transmission-of.html

TUESDAY, DECEMBER 15, 2020

OHIO TISSUE SAMPLE CONFIRMED POSITIVE FOR CHRONIC WASTING DISEASE IN ONE WILD DEER Thursday, December 10, 2020

https://chronic-wasting-disease.blogspot.com/2020/12/ohio-tissue-sample-confirmed-positive.html

THURSDAY, DECEMBER 17, 2020

Wisconsin DNR CONFIRMS CWD DETECTED IN WASHINGTON COUNTY; NEW BAITING AND FEEDING BAN NOW FOR OZAUKEE COUNTY

https://chronic-wasting-disease.blogspot.com/2020/12/wisconsin-dnr-confirms-cwd-detected-in.html

TUESDAY, DECEMBER 15, 2020

COMBATTING CHRONIC WASTING DISEASE IN PENNSYLVANIA DECEMBER 2020 PENNSYLVANIA CHRONIC WASTING DISEASE TASK FORCE

https://chronic-wasting-disease.blogspot.com/2020/12/combatting-chronic-wasting-disease-in.html

MONDAY, NOVEMBER 23, 2020

Transmissible Spongiform Encephalopathy TSE Prion Cervid Global Report November 2020

https://transmissiblespongiformencephalopathy.blogspot.com/2020/11/transmissible-spongiform-encephalopathy.html

MONDAY, NOVEMBER 23, 2020

Chronic Wasting Disease CWD TSE Prion Cervid State by State and Global Update November 2020

https://chronic-wasting-disease.blogspot.com/2020/11/chronic-wasting-disease-cwd-tse-prion.html

WEDNESDAY, OCTOBER 21, 2020

Human Prion Disease Surveillance in Washington State, 2006-2017

https://creutzfeldt-jakob-disease.blogspot.com/2020/10/human-prion-disease-surveillance-in.html

THURSDAY, NOVEMBER 19, 2020

NIH 2020 R01 NS Role of skin prions in disease transmission and diagnostic testing of human prion disease

https://creutzfeldt-jakob-disease.blogspot.com/2020/11/nih-2020-r01-ns-role-of-skin-prions-in.html

TUESDAY, NOVEMBER 17, 2020

The European Union summary report on surveillance for the presence of transmissible spongiform encephalopathies (TSE) in 2019 First published 17 November 2020

https://efsaopinionbseanimalprotein.blogspot.com/2020/11/the-european-union-summary-report-on.html

FRIDAY, OCTOBER 30, 2020

Efficient transmission of US scrapie agent by intralingual route to genetically susceptible sheep with a low dose inoculum

https://scrapie-usa.blogspot.com/2020/10/efficient-transmission-of-us-scrapie.html

2.3.2. New evidence on the zoonotic potential of atypical BSE and atypical scrapie prion strains

PLEASE NOTE;

2.3.2. New evidence on the zoonotic potential of atypical BSE and atypical scrapie prion strainsNo

https://efsa.onlinelibrary.wiley.com/doi/epdf/10.2903/sp.efsa.2020.EN-1946

WEDNESDAY, OCTOBER 28, 2020

***> EFSA Annual report of the Scientific Network on BSE-TSE 2020 Singeltary Submission

https://efsaopinionbseanimalprotein.blogspot.com/2020/10/efsa-annual-report-of-scientific.html

SUNDAY, OCTOBER 11, 2020

Bovine adapted transmissible mink encephalopathy is similar to L-BSE after passage through sheep with the VRQ/VRQ genotype but not VRQ/ARQ

https://transmissible-mink-encephalopathy.blogspot.com/2020/10/bovine-adapted-transmissible-mink.html

THURSDAY, SEPTEMBER 24, 2020

The emergence of classical BSE from atypical/ Nor98 scrapie

https://nor-98.blogspot.com/2020/09/the-emergence-of-classical-bse-from.html

FRIDAY, OCTOBER 23, 2020

Scrapie TSE Prion Zoonosis Zoonotic, what if?

https://transmissiblespongiformencephalopathy.blogspot.com/2020/10/scrapie-tse-prion-zoonosis-zoonotic.html

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

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

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

O.05: Transmission of prions to primates after extended silent incubation periods: Implications for BSE and scrapie risk assessment in human populations

Emmanuel Comoy, Jacqueline Mikol, Valerie Durand, Sophie Luccantoni, Evelyne Correia, Nathalie Lescoutra, Capucine Dehen, and Jean-Philippe Deslys Atomic Energy Commission; Fontenay-aux-Roses, France

Prion diseases (PD) are the unique neurodegenerative proteinopathies reputed to be transmissible under field conditions since decades. The transmission of Bovine Spongiform Encephalopathy (BSE) to humans evidenced that an animal PD might be zoonotic under appropriate conditions. Contrarily, in the absence of obvious (epidemiological or experimental) elements supporting a transmission or genetic predispositions, PD, like the other proteinopathies, are reputed to occur spontaneously (atpical animal prion strains, sporadic CJD summing 80% of human prion cases).

Non-human primate models provided the first evidences supporting the transmissibiity of human prion strains and the zoonotic potential of BSE. Among them, cynomolgus macaques brought major information for BSE risk assessment for human health (Chen, 2014), according to their phylogenetic proximity to humans and extended lifetime. We used this model to assess the zoonotic potential of other animal PD from bovine, ovine and cervid origins even after very long silent incubation periods.

*** We recently observed the direct transmission of a natural classical scrapie isolate to macaque after a 10-year silent incubation period,

***with features similar to some reported for human cases of sporadic CJD, albeit requiring fourfold long incubation than BSE. Scrapie, as recently evoked in humanized mice (Cassard, 2014),

***is the third potentially zoonotic PD (with BSE and L-type BSE),

***thus questioning the origin of human sporadic cases.

We will present an updated panorama of our different transmission studies and discuss the implications of such extended incubation periods on risk assessment of animal PD for human health.

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

***thus questioning the origin of human sporadic cases***

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

***our findings suggest that possible transmission risk of H-type BSE to sheep and human. Bioassay will be required to determine whether the PMCA products are infectious to these animals.

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

https://prion2015.files.wordpress.com/2015/05/prion2015abstracts.pdf

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

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

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

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

PRION 2016 TOKYO

Saturday, April 23, 2016

SCRAPIE WS-01: Prion diseases in animals and zoonotic potential 2016

Prion. 10:S15-S21. 2016 ISSN: 1933-6896 printl 1933-690X online

Taylor & Francis

Prion 2016 Animal Prion Disease Workshop Abstracts

WS-01: Prion diseases in animals and zoonotic potential

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

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

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

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

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

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

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

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

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

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

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

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

snip...

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

PMID: 6997404

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

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

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

snip...

76/10.12/4.6

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

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

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

Gibbs CJ Jr, Gajdusek DC.

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

Transmission of Scrapie to the Cynomolgus Monkey (Macaca fascicularis)

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

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

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

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

http://scrapie-usa.blogspot.com/2010/04/scrapie-and-atypical-scrapie.html

Wednesday, February 16, 2011

IN CONFIDENCE

SCRAPIE TRANSMISSION TO CHIMPANZEES

IN CONFIDENCE

http://scrapie-usa.blogspot.com/2011/02/in-confidence-scrapie-transmission-to.html

MONDAY, DECEMBER 16, 2019

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

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

What if?

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

2.3.2. New evidence on the zoonotic potential of atypical BSE and atypical scrapie prion strains

PLEASE NOTE;

2.3.2. New evidence on the zoonotic potential of atypical BSE and atypical scrapie prion strains

https://efsa.onlinelibrary.wiley.com/doi/epdf/10.2903/sp.efsa.2020.EN-1946

TUESDAY, AUGUST 18, 2009

BSE-The Untold Story - joe gibbs and singeltary 1999 - 2009

http://madcowusda.blogspot.com/2009/08/bse-untold-story-joe-gibbs-and.html

SUNDAY, AUGUST 09, 2009

CJD...Straight talk with...James Ironside...and...Terry Singeltary... 2009

http://creutzfeldt-jakob-disease.blogspot.com/2009/08/cjdstraight-talk-withjames.html