Friday, November 16, 2018

Norway atypical TSE Prion found in Fourth Moose

Finding scranty sickness on moose in Buskerud


Published 15.11.2018     Last changed 15.11.2018
- There is little drama in this discovery. We expect that we can find a few such cases a year, but since the less serious variant of the disease is concerned, we are not worried, "says Anne Marie Jahr, Department of Animal Health in the Food Safety Authority.
This is the fourth moose that has been found with atypical disease in Norway.
The elk was killed because of abnormal behavior during regular hunting in Flesberg municipality.
- This shows the importance of taking samples of animals that are found dead or appearing abnormally. We thank the hunter for vigilance in this matter. We are fully dependent on good cooperation with several parties to achieve the goal that the disease does not spread in Norway, and the hunters do a very good job, "says Jahr.
The authorities are now stepping up the surveillance of deer in the area. Even though the hunt is nearing the end, we will make it possible for the hunters in the area to submit more samples. The municipalities will receive more sampling equipment, and all hunters who wish to contribute can contact them to deliver this. We hope the hugely good job hunters have done until now, says Jahr.

Two variants of scarcity

There are two variants of scar tissue, a contagious variant and a variant that we assume is not contagious. The infectious variant is only found in wild fauna in Nordfjella.
Read more about the two variants on the Veterinary Institute's website .

Report if you see sick or dead deer

Since its inception in 2016, over 63,000 deer animals have been tested for acne disease. The Norwegian Food Safety Authority encourages anyone who travels in forest and land and who see sick or dead deer to report to the Norwegian Food Safety Authority. Symptoms of erectile dysfunction are dislocation, frequent urination and abnormal behavior, eg. animals that do not scold people.
The disease is fatal to deer, but has never been shown to infect humans, either from animals or flesh.



''There is little drama in this discovery. We expect that we can find a few such cases a year, but since the less serious variant of the disease is concerned, we are not worried, "says Anne Marie Jahr, Department of Animal Health in the Food Safety Authority.''

LOL! don't be so sure...never say never with the tse prion disease!...terry

''a contagious variant and a variant that we assume is not contagious.''

where have i heard this before???...terry

IBNC Tauopathy or TSE Prion disease, it appears, no one is sure

Posted by flounder on 03 Jul 2015 at 16:53 GMT

Greetings Plos et al, 

in reference to; 

‘’A Naturally Occurring Bovine Tauopathy Is Geographically Widespread in the UK’’

I kindly wish to comment please, as follows.

I was stunned by this report. 

This Research Report should have been titled ;

‘’It Appears A Naturally Occurring Bovine Tauopathy Is Geographically Widespread in the UK’’

>>>Thus IBNC _appears_ to be the first naturally occurring and geographically widespread tauopathy in a species other than humans.<<< 

>>>IBNC _appear_ to lack intracellular neurofibrillary tangles,<<<

>>>Thus IBNC _appears_ to be the first naturally occurring and geographically widespread tauopathy in a species other than humans<<<

>>>IBNC appears to be a complex proteinopathy with evidence for additional secondary accumulation of alpha synuclein, ubiquitin, and possibly PrP [5]. <<<

>>>however, it appears to represent a naturally-occurring predominantly 3R tauopathy in a non-primate species.<<<

>>>In the absence of any specific aetiological cause of IBNC yet identified, and based on the existing epidemiology and presence of P-tau we have considered the possibility that IBNC might also have a significant environmental component. Epidemiological investigations to explore usage of herbicides, insecticides, parasiticides and other chemicals used in agriculture would be helpful in future investigations of IBNC and might provide further insight into some causes of neurodegeneration in man.<<< 

This is supposition at best in my opinion, and at worse, I will refrain from comment.

Too many _appears_ , appears this, appears that. 

Too many _In the absence of any specific aetiological cause of IBNC yet identified_

is this what science has come to?

has science become some entwined with corporate special interest, do we change science now?

I believe that is far too early to rule out IBNC as a Transmissible Spongiform Encephalopathy TSE prion disease, either of typical or typical strain.

This is supposition at best in my opinion, and at worse, I will refrain from comment.


Too many _appears_ , appears this, appears that.


''a contagious variant and a variant that we assume is not contagious.''

wow, assume is not contagious, so we can assume that this may or may not be the case, that;

***> - There is little drama in this discovery. We expect that we can find a few such cases a year, but since the less serious variant of the disease is concerned, we are not worried, "says Anne Marie Jahr, Department of Animal Health in the Food Safety Authority.

ASSUME= suppose to be the case, without proof.

THAT'S A HELL OF A WAY TO MAKE GLOBAL LEGISLATIVE REGULATORY DECISIONS FOR TSE PRION AND HUMAN AND ANIMAL HEALTH $$$...terry

Subject: Novel Type of Chronic Wasting Disease Detected in Moose (Alces alces), Norway
Volume 24, Number 12—December 2018

Research

Novel Type of Chronic Wasting Disease Detected in Moose (Alces alces), Norway

Laura Pirisinu, Linh Tran, Barbara Chiappini, Ilaria Vanni, Michele A. Di Bari, Gabriele Vaccari, Turid Vikøren, Knut Ivar Madslien, Jørn Våge, Terry Spraker, Gordon Mitchell, Aru Balachandran, Thierry Baron, Cristina Casalone, Christer M. Rolandsen, Knut H. Røed, Umberto Agrimi, Romolo Nonno, and Sylvie L. BenestadComments to Author 

Author affiliations: Istituto Superiore di Sanità, Rome, Italy (L. Pirisinu, B. Chiappini, I. Vanni, M.A. Di Bari, G. Vaccari, U. Agrimi, R. Nonno); Norwegian Veterinary Institute, Oslo, Norway (L. Tran, T. Vikøren, K. Madslien, J. Våge, S.L. Benestad); Colorado State University, Fort Collins, Colorado, USA (T. Spraker); Canadian Food Inspection Agency, Ottawa, Ontario, Canada (G. Mitchell, A. Balachandran); Anses Lyon Unité “Maladies Neuro-Dégénératives”, Lyon, France (T. Baron); Istituto Zooprofilattico Sperimentale del Piemonte Liguria e Valle d’Aosta, Torino, Italy (C. Casalone); Norwegian Institute for Nature Research, Trondheim, Norway (C.M. Rolandsen); Norwegian University of Life Sciences, Faculty of Veterinary Science, Oslo (K.H. Røed) Suggested citation for this article

Abstract

Chronic wasting disease (CWD) persists in cervid populations of North America and in 2016 was detected for the first time in Europe in a wild reindeer in Norway. We report the detection of CWD in 3 moose (Alces alces) in Norway, identified through a largescale surveillance program. The cases occurred in 13–14-year-old female moose, and we detected an abnormal form of prion protein (PrPSc) in the brain but not in lymphoid tissues. Immunohistochemistry revealed that the moose shared the same neuropathologic phenotype, characterized by mostly intraneuronal deposition of PrPSc. This pattern differed from that observed in reindeer and has not been previously reported in CWD-infected cervids. Moreover, Western blot revealed a PrPSc type distinguishable from previous CWD cases and from known ruminant prion diseases in Europe, with the possible exception of sheep CH1641. These findings suggest that these cases in moose represent a novel type of CWD.

snip...

Results 

CWD was diagnosed in 2 moose in May 2016 in Norway’s Selbu municipality and in 1 moose in October 2017 in Lierne municipality. Selbu and Lierne are respectively located ≈300 and ≈450 km northeast of Nordfjella, where CWD in reindeer was detected in 2016. Norway is populated by several species of wild cervids with varying degrees of overlapping range. Seasonal migrations are common and distances might exceed 150 km (13–15). However, studies tracking global positioning satellite–collared moose have not documented regular seasonal migrations between Selbu and Lierne municipalities, suggesting that these can be considered different moose subpopulations.

We initially detected PrPSc in brain samples by using a rapid test and then confirmed by WB (data not shown) and IHC. Sequencing analysis of the entire PrP coding sequence revealed that the 3 moose had the wild type PrP genotype, homozygous for lysine at codon 109 and for methionine at codon 209 (KK109MM209) (GenBank accession no. MH230115).

Discriminatory PrPSc Immunohistochemistry Show Differences between Reindeer and Moose Thumbnail of Immunohistochemical detection of disease-associated prion protein in brain sections at the level of the obex in cervids with chronic wasting disease, Norway. A–E) Reindeer; F–J) moose. mAbs used were 12B2 (A, F), 9A2 (B, G), L42 (C, H), SAF 84 (D, I), and F99/97.6 (E, J). Staining obtained in the reindeer tissues are similar regardless of mAbs used (A–E). Conversely, for moose tissues, the staining was primarily observed intraneuronally with L42, SAF84, and F99/97.6 (H–J) but was no Figure 1. Immunohistochemical detection of disease-associated prion protein in brain sections at the level of the obex in cervids with chronic wasting disease, Norway. A–E) Reindeer; F–J) moose. mAbs used were 12B2 (A,...

The distribution of PrPSc staining was examined by IHC and compared in the tissues of the 3 moose and the reindeer by using 5 different antibodies (Figure 1). No staining was observed in CWD-negative reindeer and moose independently of the antibody used. The distribution of PrPSc in the reindeer was identical for each of the 5 antibodies and did not differ from the description of PrPSc distribution in North America cervids (16–18). The labeling was most consistent within the gray matter of the medulla oblongata, particularly in the dorsal motor of the vagus nerve (7). The thalamic and brain stem regions of the brain were most affected, with a minimal amount of PrPSc identified dorsal to the corpus callosum.

PrPSc labeling in the moose brains (Figure 1, panels F–J) was clearly different from that of the reindeer (Figure 1, panels A–E). In the moose, after staining with F99/97.6 and L42, PrPSc was almost exclusively observed as intraneuronal aggregates, although intraastrocytic type (multiple small granules scattered in the cytoplasm of astrocyte-resembling cells) and intramicroglial type (1 as single or a few large granules in close proximity to microglia-like nuclei) were also observed in the cerebral cortices and olfactory bulb (Technical Appendix Figure 1). The degree of PrPSc staining was more intensive and appeared more widespread in the neuropil using SAF84.

At the level of the obex, we found stained neurons in all nuclei, whereas the dorsal motor of the vagus nerve was not remarkably stained, as observed in reindeer. The intensity of labeling varied between the 3 moose; no. 2 displayed sparse labeling, no. 3 widespread and abundant labeling, and no. 1 intermediate labeling intensity. We observed PrPSc in all parts of the brain investigated except the cerebellums of moose nos. 1 and 2. A diffuse or discrete punctate staining was observed in the granular layer of the cerebellum of moose no. 3, with stronger staining in some Golgi neurons (Technical Appendix Figure 1, panel B). In all 3 moose, the cortical regions showed laminar staining of neurons in all the cell layers, especially in fusiform-shaped neurons. The neurons of the olfactory tubercle from all 3 also stained strongly, and some glia-associated staining could be observed.

In contrast to the reindeer, the downstream flexible tail mAbs 12B2 and 9A2 did not stain in the moose (Figure 1, panels F and G), suggesting that the moose PrPSc was truncated by endogenous proteases further upstream in the N terminus than was reindeer PrPSc. Contrary to previous findings in reindeer, PrPSc was not detected in the Ln from moose no. 1 or in the Ln and tonsils from moose no. 3 (lymphoid tissues were not available in moose no. 2) by either IHC or ELISA.

PrPSc from Norway Moose Compared with Other CWD Isolates from Canada and Norway Thumbnail of Western blot analysis of PrPres in brains of chronic wasting disease-affected cervids from Norway and Canada. A) Western blot analysis PrPres in brains of moose and reindeer from Norway. Membrane was probed with L42 monoclonal antibodies. Molecular weights (kDa) are indicated on the right. Tissue equivalent loaded per lane was 1 mg. B) Western blot analysis of PrPres from moose isolates from Norway (lanes 6–7) compared with PrPres from chronic wasting disease–affected elk or wapiti Figure 2. Western blot analysis of PrPres in brains of chronic wasting disease-affected cervids from Norway and Canada. A) Western blot analysis PrPres in brains of moose and reindeer from Norway. Membrane was...

We compared the PrPSc features in moose from Norway with those of other CWD isolates from Norway and Canada by discriminatory WB, which enabled comparison of PrPres by epitope mapping with different antibodies. Norway moose PrPres had a lower apparent molecular weight (MW) than PrPres from Norway reindeer (Figure 2, panel A) or from Canada isolates (Figure 2, panel B). This lower MW was explained by the occurrence of more C-terminal cleavage of PrPSc by protease K, as confirmed by the partial loss of the 12B2 epitope (Figure 2, panel B).

Thumbnail of Characterization of PrPres fragments from moose (Alces alces) in Europe by epitope mapping. Mapping with mAbs spanning the whole prion protein enabled the analysis of PrPres in moose samples before (PNGase F–) and after deglycosylation (PNGase F+), based on presence or absence of the epitopes and apparent molecular weight. Solid arrowheads indicate C-terminal fragment of ≈13 kDa fragment (present in both samples and detected with SAF84 mAbs). Open arrowheads indicate C-terminal frag Figure 3. Characterization of PrPres fragments from moose (Alces alces) in Europe by epitope mapping. Mapping with mAbs spanning the whole prion protein enabled the analysis of PrPres in moose samples before (PNGase...

Given the unusual pattern observed in moose isolates from Norway, we further investigated their biochemical characteristics with additional mAbs and by enzymatic deglycosylation (Figure 3). Moose samples showed a main C-terminal fragment of ≈17 kDa, detected with SAF84, L42, and 9A2, and an additional glycosylated C-terminal fragment of ≈13 kDa (CTF13) detected only with SAF84. The N terminal 12B2 epitope was mainly lost, although a small amount of PrPres was still detectable in moose no. 1 (Figure 3) and no. 3 (Technical Appendix Figure 2) with this antibody.

In moose nos. 2 and 3, an additional glycosylated C-terminal fragment of ≈16 kDa (CTF16) was detected by SAF84 and L42 mAbs (Figure 3; Technical Appendix Figure 2). We cannot exclude that a small amount of CTF16 was also present in moose no. 1, given that a weak PrPres fragment of ≈16 kDa was detectable upon deglycosylation and long exposure of blots (Figure 3; Technical Appendix Figure 3). Moose nos. 1 and 3 also had a nonglycosylated internal fragment of ≈10 kDa, cleaved at both N and C termini of PrPSc, which was recognized by using mAbs 9A2 (Figure 3). Moreover, the analysis of PrPres from different neuroanatomic regions showed that the slight differences observed among the 3 moose were not dependent on the area analyzed (Technical Appendix Figure 2).

Comparison of the PrPSc Features of the Norway Moose with Sheep and Cattle Prion Strains from Europe Thumbnail of Bar graph of antibody-signal ratios (y-axis) showing discrimination of the ovine, bovine, moose and reindeer samples (x-axis) analyzed in a study characterizing chronic wasting disease in moose (Alces alces), Norway. The antibody ratio is the L42/12B2 ratio of the chemiluminescence signal relative to the L42/12B2 ratio of the control scrapie loaded in each blot. Bars represent median values of >3 independent determinations; error bars represent the range of observed values. Bars Figure 4. Bar graph of antibody-signal ratios (y-axis) showing discrimination of the ovine, bovine, moose and reindeer samples (x-axis) analyzed in a study characterizing chronic wasting disease in moose (Alces alces), Norway. The...

Thumbnail of Comparison of protease-resistant PrPres from moose (Alces alces) with chronic wasting disease and from sheep with scrapie, Europe. Representative blots show epitope mapping analysis ofPrPres (lane 4, CH1641; lane 5, moose no. 1; lane 6, moose no. 2) in comparison with different ovine transmissible spongiform encephalopathy isolates (lane 1, atypical/Nor98; lane 2, classical scrapie; and lane 3, CH1641). A chronic wasting disease isolate from Canada was loaded as control (lane 7). Th Figure 5. Comparison of protease-resistant PrPres from moose (Alces alces) with chronic wasting disease and from sheep with scrapie, Europe. Representative blots show epitope mapping analysis ofPrPres (lane 4, CH1641; lane 5, moose...

Comparison with ovine and bovine prions was performed to determine the N terminal cleavage of the main PrPres fragment by analyzing the different PrPres fragments in each sample, the MW of these fragments, and the L42/12B2 antibody ratio (Figure 4; Technical Appendix Table). Among ovine prions, classical scrapie and atypical/Nor98 were easily discriminated from moose isolates (Figure 5). Classical scrapie PrPres had a higher MW than moose PrPres, as confirmed by the preservation of 12B2 epitope. As previously observed (19), Nor98 PrPres was cleaved at both the N and C termini, and the characteristic 11–12 kDa band was detected by L42, 9A2, and 12B2 mAbs (Figure 5). In contrast, CH1641 samples showed molecular features partially overlapping with the moose (Figure 5). CH1641 samples showed a PrPres of ≈17 kDa and were accompanied by an additional C-terminal fragment of 13–14 kDa detected by using SAF84 mAbs (20). However, CTF16 and the internal PrPres fragment of 10 kDa could not be detected in CH1641 samples.

Thumbnail of Comparison of protease-resistant core of abnormal form of prion protein from moose (Alces alces) in Europe with chronic wasting disease and from cattle with BSE. Representative blots show epitope mapping analysis of protease-resistant core of abnormal form of prion protein in moose (lane 5, moose no. 1; lane 6, moose no. 2) in comparison with different BSE isolates (lane 2, classical BSE; lane 3, H-type BSE; and lane 4, L-type BSE). A sheep scrapie isolate was loaded as control (lan Figure 6. Comparison of protease-resistant core of abnormal form of prion protein from moose (Alces alces) in Europe with chronic wasting disease and from cattle with BSE. Representative blots show epitope mapping analysis...

Moose PrPSc did not overlap with any type of bovine PrPSc. The lack of the 12B2 epitope in moose PrPres was similar to C-type and L-type atypical BSE, but the 2 bovine prions had neither CTF13, CTF16, nor the internal fragment (Figure 6). H-type atypical BSE showed the CTF13 and the internal fragment similar to moose PrPres, but the main PrPres fragment showed a higher MW and preserved the 12B2 epitope (Figure 6).

The ratio of reactivity obtained with L42 and 12B2 antibodies reflected the N terminal cleavage of the main fragment of PrPSc, enabling confirmation that the differences observed in MW of PrPres actually depend on different N terminal proteinase K cleavage, irrespective of the host species (Figure 4). Values >2 are indicative of BSE-like cleavage, whereas values <1 12b2="" a="" behavior="" better="" bse-like="" compared="" epitope="" in="" indicate="" moose="" of="" preservation="" prpres="" ratio="" respect="" scrapie.="" the="" this="" was="" with="">2). However, moose no. 1 had a ratio lower than moose nos. 2 and 3. The CH1641-like field sample was similar to moose no. 1 in this respect, whereas CH1641 was similar to moose nos. 2 and 3. Finally, the value <1 and="" appendix="" atypical="" bse="" canada="" classical="" compared="" cwd="" div="" for="" from="" h-type="" higher="" in="" isolates="" mw="" observed="" online="" prpres="" reflected="" reindeer="" scrapie="" table="" technical="" their="" with="">

Discussion 

Although CWD has been detected in several captive and free-ranging cervid species from a large geographic area in North America, <10 3="" a="" although="" america="" and="" as="" associated="" atypical="" be="" been="" bovines="" bse="" can="" cases="" classical="" cwd="" described="" differing="" directly="" disease="" diseases="" div="" existence="" far.="" for="" from="" h-type="" has="" have="" hosts="" identification="" ihc="" in="" inferred="" is="" known="" l-type="" molecular="" moose="" natural="" naturally="" new="" north="" norway.="" norway="" not="" observed="" occurring="" of="" often="" or98="" or="" phenomenon="" phenotype="" phenotypes="" phenotypic="" previously="" prion="" reindeer="" report="" reported="" scrapie.="" sheep="" showed="" so="" strain.="" strain="" studies="" suggestive="" that="" the="" this="" those="" transmission="" variation="" variations="" we="" well="" with="">

The phenotype variant found in moose from Norway could be hypothetically attributed to host species factors. To address this issue, we directly compared PrPSc characteristics in the Norway moose with those in a Canada moose with CWD. In agreement with the available evidence, we found that the Canada moose PrPSc had features different from Norway moose PrPSc and were indistinguishable from other cervids with classical CWD. This finding suggests that the variant PrPSc type observed in Norway moose could not simply reflect a host species factor. Notably, in both natural and experimental conditions, CWD-affected moose in North America have been reported to display disease features indistinguishable from CWD in other cervids and had detectable PrPSc in lymphoid tissues (21,27).

Species-specific amino acid polymorphisms in the cervid PrP are associated with CWD susceptibility, incubation time, and pathology (28–30). In transmission experiments, atypical features were reported in elk or wapiti and mule deer with genotypes associated with a relative resistance to disease, extension of the incubation period, or both (31,32). Moose PrP is polymorphic at codon 109 (K/Q) and 209 (M/I), combined in 3 alleles: K109M209 (observed in Europe and North America), Q109M209 (observed in Europe), and K109I209 (observed in North America) (33,34). The 3 moose with CWD from Norway had the KK109MM209 genotype, whereas the moose case from Canada used for comparison had KK109II209 genotype. Thus, we cannot exclude that the differences observed between Norway and Canada moose in our study are dependent on differences in PrP genotype. However, a classical CWD phenotype has been reported in naturally (21) and experimentally infected (27) moose with the KK109MM209 genotype, suggesting that a difference at PrP codon 209 is probably not the cause of the variant phenotype observed in moose in Norway. All of these findings suggest that neither the species nor the individual PrP genotypes are likely to have caused the variant phenotypes observed and imply that this variant phenotype could represent a novel CWD strain.

CWD is known to be a highly contagious disease in North America; however, data relating to the disease in moose is sparse and insufficient to understand the epidemiology and the implications of CWD in this species. The apparent low CWD prevalence reported for moose in North America compared with other cervid species might be attributable to the individual social behavior of moose and the minimal habitat overlap between moose and other cervids in areas with CWD. Additionally, surveillance program design, disease variability, and host genetics might influence the prevalence of the disease. Based on the epizootic dynamics in North America, CWD plausibly could have become established in reindeer in Norway more than a decade ago (35). In this scenario, the disease in moose could possibly be linked to the disease observed in reindeer, with strain mutation or phenotype shift putatively caused by interspecific transmission. However, a main cause of strain mutation after interspecies transmission (i.e., PrP amino acid differences between the donor and host species) is not relevant in this case because reindeer and moose share the same PrP primary sequence. An alternative hypothesis could be that moose have a prion disease which is independent of the reindeer epidemic, being either specific to the Norwegian moose or acquired by species other than the reindeer.

The 3 moose were 13, 14, and 13 years of age. Although moose can reach ages beyond 20 years, we consider these moose as old because female moose >10–12 years of age start to show signs of senescence and declining survival and reproduction rates (36,37). The old age of the moose, the absence of lymphoid tissue involvement, and the low disease prevalence observed so far (3 of 10,531 moose tested) could suggest that CWD in moose is less contagious than classical CWD or could represent a spontaneous TSE. The finding that the affected moose were from the same geographic area does not seem to support a spontaneous origin of the disease; however, the actual evidence for geographic clustering could have been biased by oversampling in Trøndelag County, where the first positive moose was detected. Lack of detailed data on the ages of the moose tested so far in different geographic areas prevents any definitive conclusion. Still, the recent detection of a positive moose in Finland, several hundred kilometers from Trøndelag County, might indicate that the disease is not restricted to Norway (38). The ongoing intensive surveillance in Norway and several European Union countries with large moose populations will help to better clarify the actual geographic distribution and prevalence and will be critical for understanding the contagious or spontaneous nature of the disease.

The 3 moose analyzed shared a distinctive IHC pattern, mainly characterized by intraneuronal accumulation of PrPSc, and common PrPSc features, such as the proteinase K N-terminal cleavage and the presence of an additional CTF13 fragment. However, we also observed unexpected differences among the 3 moose. By WB, the CTF16 fragment was observed in moose nos. 2 and 3 but not in moose no. 1, whereas the nonglycosylated internal fragment of 10 kDa was evident in moose nos. 1 and 3 but could not be detected in moose no. 2. Furthermore, we also showed that these differences did not depend on the brain area investigated. We cannot rule out that these slight differences might depend on technical issues rather than represent actual PrPSc variations. The outcome of the ongoing bioassay experiments will help to clarify the meaning of the observed variations.

By comparing the moose PrPSc features with other animal TSEs circulating in Europe, we found no evidence of similarities with bovine and ovine prions. Minimal similarities were observed with CH1641 samples; however, CH1641 cases have not yet been detected in Norway. Bioassay in a large spectrum of rodent models will assist in determining whether these molecular similarities imply biologic association between the atypical CWD in moose and small ruminant CH1641. Transmission studies in several rodent models are underway and will help to clarify whether the different phenotype observed (designated Nor16CWD) could reflect the presence of a new cervid prion strain in moose from Norway.

Dr. Pirisinu is a researcher at the Istituto Superiore di Sanità in Rome, Italy. Her primary research interests include the prion strain characterization and zoonotic potential of animal prion diseases.

Acknowledgments



TUESDAY, JUNE 13, 2017 

PRION 2017 CONFERENCE 

ABSTRACT 

Chronic Wasting Disease in European moose is associated with PrPSc features different from North American CWD 

P178 Chronic Wasting Disease in European moose is associated with PrPSc features different from North American CWD

Dr Laura Pirisinu1, Dr Linh Tran2, Dr Gordon Mitchell3, Dr Aru Balachandran3, Dr Thierry Baron4, Dr Cristina Casalone5, Dr Michele Di Bari1, Dr Umberto Agrimi1. Dr Romolo Nonno1, Dr Sylvie Benestad2 

1Department of Veterinary Public Health and Food Safety, Istituto Superiore di Sanita, Rome, Italy, 2Norwegian Veterinary Institute, Oslo, Norway, 3Canadian Food Inspection Agency, National and OlE Reference Laboratory for Scrapie and CWD, Ottawa Laboratory Fallowfield, Ottawa, Canada, 4Neurodeqenerative Diseases Unit, ANSES - French Agency for Food, Environmental and Occupational Health & Safety, Lyon, France, 5Istituto Zooprofilattico Sperimentale del Pietnonte, Liguria e Valle d'Aosta, Turin, Italy 

Aims: In 2016, Chronic Wasting Disease (CWD) was detected for the first time in Europe in three wild Norwegian reindeer (Rangifer tarandus tarandus) and in two moose (Alces alces). The biochemical analysis and the immunohistochemical distribution of PrPSc from Norwegian reindeer revealed a pattern similar to North American (NA) isolates1. In this study, we studied the biochemical features of PrPSc from the two CWD cases in Norwegian moose. 

Methods: Western blot (WB) analysis of PK-treated PrPSc (PrPres) from Norwegian moose and reindeer isolates was performed according to the ISS discriminatory WB protocol (used in BSE and scrapie Italian surveillance). PrPres fragments were determined by epitope mapping (SAF84, L42, 9A2, 12B2 mAbs), before and after deglycosylation. CWD isolates from Canadian cervids (wapiti, moose and white tailed deer) and a panel of small ruminant and bovine prion strains circulating in Europe were also analysed. 

Results: WB analysis with different mAbs showed that PrPres from both Norwegian moose samples was different from that usually associated with CWD in cervids. Indeed, their main C-terminal fragment had a MW lower than the other CWD isolates, and could be discriminated by the absence of the 12B2 epitope. Furthermore, while NA CWD PrPSc is composed of a single PrPres fragment, Norwegian moose samples had an additional C-terminal PrPres fragment of ~13 kDa (CTF13). Among ovine TSEs, classical scrapie and Nor98 were discriminated from both Norwegian moose isolates, while CH1641 samples had molecular features partially overlapping with the moose, i.e. a low MW PrPres and the presence of CTF13. In contrast, moose PrPSc did not overlap with any bovine PrPSc. Indeed, the MW of moose PrPres was lower than H-BSE and similar to C-BSE and L-BSE PrPres, but the two bovine prions lacked additional PrPres fragments. 

Conclusions: Unexpectedly, PrPSc from Norwegian moose revealed features substantially different from all other CWD isolates. The PrPSc pattern of Norwegian moose was also different from Canadian moose, suggesting that the variant PrPSc type observed does not simply reflect a host factor and could represent a new CWD strain. Furthermore, PrPSc of Norwegian moose can be easily discriminated from all BSE types, classical scrapie and Nor98, while showing significant overlapping only with CH1641. Bioassay in voles will help to clarify whether the different PrPSc types observed reflect the presence of a new CWD strain in Norwegian moose, and its relationships with known animal TSEs. 

References: 1Benestad et al, Vet Res (2016}47:88 

PRION 2017 DECIPHERING NEURODEGENERATIVE DISORDERS


please see;

***Our transmission study demonstrates that CH 1641-like scrapie is likely to be more virulent than classical scrapie in cattle. 

In the US, scrapie is reported primarily in sheep homozygous for 136A/171Q (AAQQ) and the disease phenotype is similar to that seen with experimental strain CH1641.


***Our transmission study demonstrates that CH 1641-like scrapie is likely to be more virulent than classical scrapie in cattle. 

P-088 Transmission of experimental CH1641-like scrapie to bovine PrP overexpression mice

Kohtaro Miyazawa1, Kentaro Masujin1, Hiroyuki Okada1, Yuichi Matsuura1, Takashi Yokoyama2

1Influenza and Prion Disease Research Center, National Institute of Animal Health, NARO, Japan; 2Department of Planning and General Administration, National Institute of Animal Health, NARO

Introduction: Scrapie is a prion disease in sheep and goats. CH1641-lke scrapie is characterized by a lower molecular mass of the unglycosylated form of abnormal prion protein (PrpSc) compared to that of classical scrapie. It is worthy of attention because of the biochemical similarities of the Prpsc from CH1641-like and BSE affected sheep. We have reported that experimental CH1641-like scrapie is transmissible to bovine PrP overexpression (TgBoPrP) mice (Yokoyama et al. 2010). We report here the further details of this transmission study and compare the biological and biochemical properties to those of classical scrapie affected TgBoPrP mice.

Methods: The details of sheep brain homogenates used in this study are described in our previous report (Yokoyama et al. 2010). TgBoPrP mice were intracerebrally inoculated with a 10% brain homogenate of each scrapie strain. The brains of mice were subjected to histopathological and biochemical analyses.

Results: Prpsc banding pattern of CH1641-like scrapie affected TgBoPrP mice was similar to that of classical scrapie affected mice. Mean survival period of CH1641-like scrapie affected TgBoPrP mice was 170 days at the 3rd passage and it was significantly shorter than that of classical scrapie affected mice (439 days). Lesion profiles and Prpsc distributions in the brains also differed between CH1641-like and classical scrapie affected mice.

Conclusion: We succeeded in stable transmission of CH1641-like scrapie to TgBoPrP mice. Our transmission study demonstrates that CH 1641-like scrapie is likely to be more virulent than classical scrapie in cattle.

snip...

RESEARCH ARTICLE

Phenotype Shift from Atypical Scrapie to CH1641 following Experimental Transmission in Sheep

Marion M. Simmons*, S. Jo Moore¤a, Richard Lockey¤b, Melanie J. Chaplin, Timm Konold, Christopher Vickery, John Spiropoulos

Animal and Plant Health Agency—Weybridge, Woodham Lane, Addlestone, Surrey, KT15 3NB, United Kingdom

¤a Current address: School of Veterinary and Biomedical Sciences, Murdoch University, South Street, Murdoch, Western Australia, 6150, Australia

¤b Current address: University of Southampton, Southampton, SO17 1BJ, United Kingdom * marion.simmons@apha.gsi.gov.uk

Abstract

The interactions of host and infecting strain in ovine transmissible spongiform encephalopathies are known to be complex, and have a profound effect on the resulting phenotype of disease. In contrast to classical scrapie, the pathology in naturally-occurring cases of atypical scrapie appears more consistent, regardless of genotype, and is preserved on transmission within sheep homologous for the prion protein (PRNP) gene. However, the stability of transmissible spongiform encephalopathy phenotypes on passage across and within species is not absolute, and there are reports in the literature where experimental transmissions of particular isolates have resulted in a phenotype consistent with a different strain. In this study, intracerebral inoculation of atypical scrapie between two genotypes both associated with susceptibility to atypical forms of disease resulted in one sheep displaying an altered phenotype with clinical, pathological, biochemical and murine bioassay characteristics all consistent with the classical scrapie strain CH1641, and distinct from the atypical scrapie donor, while the second sheep did not succumb to challenge. One of two sheep orally challenged with the same inoculum developed atypical scrapie indistinguishable from the donor. This study adds to the range of transmissible spongiform encephalopathy phenotype changes that have been reported following various different experimental donor-recipient combinations. While these circumstances may not arise through natural exposure to disease in the field, there is the potential for iatrogenic exposure should current disease surveillance and feed controls be relaxed. Future sheep to sheep transmission of atypical scrapie might lead to instances of disease with an alternative phenotype and onward transmission potential which may have adverse implications for both public health and animal disease control policies.

snip...

Despite naturally-occurring atypical scrapie being observed in a range of genotypes, successful experimental transmissions of clinical disease have so far only been reported within a particular homologous donor-recipient genotype model using sheep which are AHQ/AHQ homozygous [8,15,16]. These published transmissions represent part of a large study at APHA which has been running since 2004, investigating the potential transmissibility of atypical scrapie in a range of both homologous and cross-genotype combinations. Here we describe an unexpected and interesting finding from that study where one experimental challenge in which atypical scrapie from an ARR/ARR donor was inoculated intracerebrally into two AHQ/AHQ recipient sheep, and in one of them the resulting disease had a phenotype that was indistinguishable from CH1641 [29], a classical scrapie strain which has some BSE-like Western blot properties.


*** One of these isolates (TR316211) behaved like the CH1641 isolate, with PrPres features in mice similar to those in the sheep brain. From two other isolates (O100 and O104), two distinct PrPres phenotypes were identified in mouse brains, with either high (h-type) or low (l-type) apparent molecular masses of unglycosylated PrPres, the latter being similar to that observed with CH1641, TR316211, or BSE. Both phenotypes could be found in variable proportions in the brains of the individual mice. In contrast with BSE, l-type PrPres from "CH1641-like" isolates showed lower levels of diglycosylated PrPres. From one of these cases (O104), a second passage in mice was performed for two mice with distinct PrPres profiles. This showed a partial selection of the l-type phenotype in mice infected with a mouse brain with predominant l-type PrPres, and it was accompanied by a significant increase in the proportions of the diglycosylated band. These results are discussed in relation to the diversity of scrapie and BSE strains.


Subject: more on scrapie/BSE strain CH1641

From: tom

Reply-To: Bovine Spongiform Encephalopathy

Date: Sun, 10 Jan 1999 21:52:05 -0800

Content-Type: text/plain

Parts/Attachments: Parts/Attachments text/plain (37 lines) Reply Reply

Recall a forthcoming J Gen Virol Jan 1999 v80:1 - 4 says there are similarities between BSE and an experimental isolate of natural scrapie, CH1641. This might then be the long-sought missing scrapie strain that could have given rise to the BSE epidemic. It would raise additional questions about the harmlessness to humans of scrapie.

On the other hand, CH1641 happened to be one of the scrapie strains studied very recently by Collinge's group, Neurosci Lett. 1998 Oct 23;255(3):159-62. It did not have the prp-sc type identical to BSE passaged in sheep.

The CH1641 strain is mentioned only twice before in Medline abstracts (though there could be many fulltext mentions), one of these being the original naming of the strain in 1988:

The unusual properties of CH1641, a sheep-passaged isolate of scrapie.

Foster JD, Dickinson AG Vet Rec 1988 Jul 2;123(1):5-8

An isolate of scrapie designated CH1641 was identified from a natural case of scrapie in a Cheviot sheep by passage in sheep and goats. It has not been possible to transmit scrapie to mice from this source. The Sip gene which controls the incubation periods of experimental scrapie in Cheviot sheep has two alleles; sA which shortens and pA which lengthens the incubation periods of most strains of scrapie after the first experimental injection in sheep (the A group of strains). The CH1641 isolate differs from them in that the alleles of Sip act in the opposite way, with incubation being shorter in the pA homozygotes. There is some evidence that one or more genes, in addition to Sip, may be implicated in the control of scrapie incubation in sheep and the possibility of a carrier infection with CH1641 is also discussed.

Novel polymorphisms in the caprine PrP gene: a codon 142 mutation associated with scrapie incubation period.

J Gen Virol 1996 Nov;77 ( Pt 11):2885-91 Published erratum appears in J Gen Virol 1997 Mar;78(Pt 3):697 Goldmann W, Martin T, Foster J, Hughes S, Smith G, Hughes K, Dawson M, Hunter N

Age at disease onset and rate of progression of transmissible spongiform encephalopathies in man, sheep and mice are modulated by the host genome, in particular by the PrP gene and its allelic forms. Analysis of the caprine PrP gene revealed several different alleles. Four PrP protein variants were found, three of which were goat specific with single amino acid changes at codons 142, 143 and 240. The fourth was identical to the most common sheep PrP protein variant (Ala136-Arg154-Gln171). The dimorphism at codon 142 (Ile --> Met) appeared to be associated with differing disease incubation periods in goats experimentally infected with isolates of bovine spongiform encephalopathy, sheep scrapie CH1641 or sheep-passaged ME7 scrapie.




TSE PRION UPDATE USA 2012

re-BSE in goats can be mistaken for scrapie


Wednesday, January 18, 2012

BSE IN GOATS CAN BE MISTAKEN FOR SCRAPIE

February 1, 2012


Wednesday, January 18, 2012

Selection of Distinct Strain Phenotypes in Mice Infected by Ovine Natural Scrapie Isolates Similar to CH1641 Experimental Scrapie

Journal of Neuropathology & Experimental Neurology:

February 2012 - Volume 71 - Issue 2 - p 140–147


Monday, March 21, 2011

Sheep and Goat BSE Propagate More Efficiently than Cattle BSE in Human PrP Transgenic Mice

snip...

On the other hand, this component would not be distinguishable from bovine-passaged BSE prions due to the current limits of the standard biological methods and/or the molecular tools employed here to characterize prion strains. Whatever the mechanism, the notion that a passage through an intermediate species can profoundly alter prion virulence for the human species has important public-health issues, regarding emerging and/or expanding TSEs, like atypical scrapie or CWD.

snip...

Taken all together, our results suggest that the possibility of a small ruminant BSE prion as vCJD causal agent could not be ruled out, which has important implications on public and animal health policies. On one hand, although the exact magnitude and characteristic of the vCJD epidemic is still unclear, its link with cattle BSE is supported by strong epidemiological ground and several experimental data. On the other hand, the molecular typing performed in our studies, indicates that the biochemical characteristics of the PrPres detected in brains of our sheep and goat BSE-inoculated mice seem to be indistinguishable from that observed in vCJD. Considering the similarity in clinical manifestation of BSE- and scrapie-affected sheep [48], a masker effect of scrapie over BSE, as well as a potential adaptation of the BSE agent through subsequent passages, could not be ruled out. As BSE infected sheep PrPSc have been detected in many peripheral organs, small ruminant-passaged BSE prions might be a more widespread source of BSE infectivity compared to cattle [19], [49], [50]. 

*** This fact is even more worrying since our transmission studies suggest that apparently Met129 human PrP favours a BSE agent with ovine rather than a bovine sequence. Finally, it is evident that, although few natural cases have been described and so far we cannot draw any definitive conclusion about the origin of vCJD, we can not underestimate the risk of a potential goat and/or sheep BSE agent.

snip...


Technical Abstract:

Prion strains may vary in their ability to transmit to humans and animals. Few experimental studies have been done to provide evidence of differences between U.S. strains of scrapie, which can be distinguished by incubation times in inbred mice, microscopic lesions, immunoreactivity to various antibodies, or molecular profile (electrophoretic mobility and glycoform ratio). Recent work on two U.S. isolates of sheep scrapie supports that at least two distinct strains exist based on differences in incubation time and genotype of sheep affected. One isolate (No. 13-7) inoculated intracerebrally caused scrapie in sheep AA at codon 136 (AA136) and QQ at codon 171 (QQ171) of the prion protein in an average of 19 months post-inoculation (PI) whereas a second isolate (No. x124) caused disease in less than 12 months after oral inoculation in AV136/QQ171 sheep. Striking differences were evident when further strain analysis was done in R111, VM, C57Bl6, and C57Bl6xVM (F1) mice. No. 13-7 did not induce disease in any mouse strain at any time post-inoculation (PI) nor were brain tissues positive by western blot (WB). Positive WB results were obtained from mice inoculated with isolate No. x124 starting at day 380 PI. Incubation times averaged 508, 559, 601, and 633 days PI for RIII, C57Bl6, VM, and F1 mice, respectively. Further passage will be required to characterize these scrapie strains in mice. This work provides evidence that multiple scrapie strains exist in U.S. sheep.


One of these isolates (TR316211) behaved like the CH1641 isolate, with PrPres features in mice similar to those in the sheep brain. From two other isolates (O100 and O104), two distinct PrPres phenotypes were identified in mouse brains, with either high (h-type) or low (l-type) apparent molecular masses of unglycosylated PrPres, the latter being similar to that observed with CH1641, TR316211, or BSE. Both phenotypes could be found in variable proportions in the brains of the individual mice. In contrast with BSE, l-type PrPres from "CH1641-like" isolates showed lower levels of diglycosylated PrPres. From one of these cases (O104), a second passage in mice was performed for two mice with distinct PrPres profiles. This showed a partial selection of the l-type phenotype in mice infected with a mouse brain with predominant l-type PrPres, and it was accompanied by a significant increase in the proportions of the diglycosylated band. These results are discussed in relation to the diversity of scrapie and BSE strains.


In the US, scrapie is reported primarily in sheep homozygous for 136A/171Q (AAQQ) and the disease phenotype is similar to that seen with experimental strain CH1641.


snip...see ;


Thursday, July 14, 2011

Histopathological Studies of "CH1641-Like" Scrapie Sources Versus Classical Scrapie and BSE Transmitted to Ovine Transgenic Mice (TgOvPrP4)


SHEEP AND BSE

PERSONAL AND CONFIDENTIAL

SHEEP AND BSE

A. The experimental transmission of BSE to sheep.

Studies have shown that the ''negative'' line NPU flock of Cheviots can be experimentally infected with BSE by intracerebral (ic) or oral challenge (the latter being equivalent to 0.5 gram of a pool of four cow brains from animals confirmed to have BSE).


RB264

BSE - TRANSMISSION STUDIES


Wednesday, January 18, 2012

Selection of Distinct Strain Phenotypes in Mice Infected by Ovine Natural Scrapie Isolates Similar to CH1641 Experimental Scrapie

Journal of Neuropathology & Experimental Neurology:

February 2012 - Volume 71 - Issue 2 - p 140–147




***however in 1 C-type challenged animal, Prion 2015 Poster Abstracts 

S67 PrPsc was not detected using rapid tests for BSE.

***Subsequent testing resulted in the detection of pathologic lesion in unusual brain location and PrPsc detection by PMCA only.

*** IBNC Tauopathy or TSE Prion disease, it appears, no one is sure ***

Posted by Terry S. Singeltary Sr. on 03 Jul 2015 at 16:53 GMT



Discussion: The C, L and H type BSE cases in Canada exhibit molecular characteristics similar to those described for classical and atypical BSE cases from Europe and Japan.

*** This supports the theory that the importation of BSE contaminated feedstuff is the source of C-type BSE in Canada.

*** It also suggests a similar cause or source for atypical BSE in these countries. ***

see page 176 of 201 pages...tss


*** Singeltary reply ; Molecular, Biochemical and Genetic Characteristics of BSE in Canada Singeltary reply;



FINLAND MOOSE FOUND DEAD IN FOREST WITH CHRONIC WASTING DISEASE 8.3.2018 12:56 

The chronic wasting disease (CWD) has been found in a moose or European elk (Alces alces) for the first time ever in Finland. The disease was diagnosed in Kuhmo in a 15-year old moose that had died naturally. The results of the analyses carried out by Finnish Food Safety Authority Evira have been verified by a EU reference laboratory. Species of the deer family, known as “cervids”, can suffer from the chronic wasting disease, and it is always fatal. The disease is not known to have been contracted by people.

Norway was before this case the only European country where CWD has been diagnosed. The monitoring of the occurrence of the disease was intensified from the beginning of 2018 in Finland and five other EU Member States.

In Finland, the occurrence of the disease has been studied already since 2003. None of the ca. 2 500 samples analysed so far had tested positive for the disease. The monitoring of the disease will now be further intensified in the Kuhmo and Kainuu region. Hunters are going to be provided with more instructions before the start of the next hunting season, if appropriate.

The chronic wasting disease is not known to have been contracted by people. Moose meat is safe to eat and no restrictions are imposed on the sales and exportation of meat of animals of the deer family. As a precautionary measure the export of live animals of the deer family to other countries will be discontinued for now.

CWD is a slowly progressing disease of deer, elk, reindeer, and moose which always leads to death. The chronic wasting disease is a prion disease and related to the BSE (bovine spongiform encephalopathy) and other TSE diseases (transmissible spongiform encephalopathy). The disease is common in North America. The moose found in Kuhmo did not suffer from the North American, highly contagious form of the chronic wasting disease. The disease seems to resemble most the form of cervid TSE diagnosed in Norway, which appears to be found incidentally in individual animals of the deer family.

For more information, please contact:

Leena Räsänen, Director, tel. +358 50 388 6518 (Food Safety)

Terhi Laaksonen, Head of Unit, tel. +358 40 159 5812 (Control of Animal Diseases)

Sirkka-Liisa Korpenfelt, Senior Resarcher, tel. + 358 50 351 0308 (Laboratory Analyses)

Antti Oksanen, Research Professor, tel. +358 44 561 6491 (Wild Animal Diseases)

Kajsa Hakulin, Ministerial Advisor, Ministry of Agriculture and Forestry, tel. +358 295 162361 (National and EU Legislation)


SATURDAY, MARCH 10, 2018

Chronic Wasting Disease CWD TSE Prion Goes Global Finland Falls, Behind Norway and S. Korea

FINLAND REPORTS FIRST CASE OF CHRONIC WASTING DISEASE CWD TSE PRION IN A moose or European elk (Alces alces)


THURSDAY, OCTOBER 25, 2018 

***> Norway New additional requirements for imports of hay and straw for animal feed from countries outside the EEA due to CWD TSE Prion


SATURDAY, NOVEMBER 10, 2018 

Canada Saskatchewan New Case Of CWD TSE PRION Detected Near Melfort Released on November 7, 2018


SUNDAY, OCTOBER 28, 2018 

Alberta, Canada 2017 Fall CWD TSE Prion Surveillance Results


TUESDAY, OCTOBER 30, 2018 

Québec federal officials found third case Chronic Wasting Disease CWD domestic red deer on a farm reported Boileau


SATURDAY, NOVEMBER 10, 2018 

***> cwd, bse, scrapie, cjd, tse prion updated November 10 2018


USA MAD COW CASE 2018 FLORIDA

WEDNESDAY, SEPTEMBER 26, 2018 

JAVMA In Short Update USDA announces detection of atypical BSE


WEDNESDAY, OCTOBER 24, 2018 

Experimental Infection of Cattle With a Novel Prion Derived From Atypical H-Type Bovine Spongiform Encephalopathy


TUESDAY, AUGUST 07, 2018 

Passage of scrapie to deer results in a new phenotype upon return passage to sheep


TUESDAY, APRIL 24, 2018 

ARS Research atypical Nor98 and Michigan Scrapie, CWD, CJD and mad cow feed 

Research Project: Genetic Impact and Improved Diagnostics for Sheep and Goat Transmissible Spongiform Encephalopathies 


THURSDAY, NOVEMBER 01, 2018 

National Scrapie Eradication Program September 2018 Monthly Report Fiscal Year 2018 October 15, 2018


THURSDAY, OCTOBER 04, 2018 

Cervid to human prion transmission 5R01NS088604-04 Update


SUNDAY, NOVEMBER 11, 2018 

Novel Type of Chronic Wasting Disease Detected in Moose (Alces alces), Norway


Cervid to human prion transmission 

Kong, Qingzhong 

Case Western Reserve University, Cleveland, OH, United States

Abstract 

Prion disease is transmissible and invariably fatal. Chronic wasting disease (CWD) is the prion disease affecting deer, elk and moose, and it is a widespread and expanding epidemic affecting 22 US States and 2 Canadian provinces so far. CWD poses the most serious zoonotic prion transmission risks in North America because of huge venison consumption (>6 million deer/elk hunted and consumed annually in the USA alone), significant prion infectivity in muscles and other tissues/fluids from CWD-affected cervids, and usually high levels of individual exposure to CWD resulting from consumption of the affected animal among often just family and friends. However, we still do not know whether CWD prions can infect humans in the brain or peripheral tissues or whether clinical/asymptomatic CWD zoonosis has already occurred, and we have no essays to reliably detect CWD infection in humans. 

We hypothesize that: 

(1) The classic CWD prion strain can infect humans at low levels in the brain and peripheral lymphoid tissues; 

(2) The cervid-to-human transmission barrier is dependent on the cervid prion strain and influenced by the host (human) prion protein (PrP) primary sequence; 

(3) Reliable essays can be established to detect CWD infection in humans; and 

(4) CWD transmission to humans has already occurred. We will test these hypotheses in 4 Aims using transgenic (Tg) mouse models and complementary in vitro approaches. 

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

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

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

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

Public Health Relevance

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

 Funding Agency

Agency

National Institute of Health (NIH)

Institute

National Institute of Neurological Disorders and Stroke (NINDS)

Type

Research Project (R01)

Project #

5R01NS088604-04

Application #

9517118

Study Section

Cellular and Molecular Biology of Neurodegeneration Study Section (CMND)

Program Officer Wong, May

Project Start 2015-09-30 Project End 2019-07-31 Budget Start 2018-08-01 Budget End 2019-07-31 Support Year 4 Fiscal Year 2018 Total Cost Indirect Cost Institution Name Case Western Reserve University Department Pathology Type Schools of Medicine DUNS # 077758407 City Cleveland State OH Country United States Zip Code 44106

 Related projects

NIH 2018 R01 NS Cervid to human prion transmission Kong, Qingzhong / Case Western Reserve University 

NIH 2017 R01 NS Cervid to human prion transmission Kong, Qingzhong / Case Western Reserve University 

NIH 2016 R01 NS Cervid to human prion transmission Kong, Qingzhong / Case Western Reserve University 

NIH 2015 R01 NS Cervid to human prion transmission Kong, Qingzhong / Case Western Reserve University $337,507




Volume 24, Number 8—August 2018

ALSO, I FIND THIS VERY DISTURBING...SEE;


***> Prion 2018 P74 High Prevalence of CWD prions in male reproductive samples 

Carlos Kramm (1,2), Ruben Gomez-Gutierrez (1,3), Tracy Nichols (4), Claudio Soto (1) and Rodrigo Morales (1) 




ZOONOTIC CHRONIC WASTING DISEASE CWD TSE PRION UPDATE

here is the latest;

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. <***
 

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

 
 


 
 
2018 CWD ***> just out CDC...see;


Volume 24, Number 8—August 2018

 
Research
 
Susceptibility of Human Prion Protein to Conversion by Chronic Wasting Disease Prions
 
Marcelo A. BarriaComments to Author , Adriana Libori, Gordon Mitchell, and Mark W. Head Author affiliations: National CJD Research and Surveillance Unit, University of Edinburgh, Edinburgh, Scotland, UK (M.A. Barria, A. Libori, M.W. Head); National and OIE Reference Laboratory for Scrapie and CWD, Canadian Food Inspection Agency, Ottawa, Ontario, Canada (G. Mitchell)
 
M. A. Barria et al.
 
ABSTRACT
 
Chronic wasting disease (CWD) is a contagious and fatal neurodegenerative disease and a serious animal health issue for deer and elk in North America. The identification of the first cases of CWD among free-ranging reindeer and moose in Europe brings back into focus the unresolved issue of whether CWD can be zoonotic like bovine spongiform encephalopathy. We used a cell-free seeded protein misfolding assay to determine whether CWD prions from elk, white-tailed deer, and reindeer in North America can convert the human prion protein to the disease-associated form. We found that prions can convert, but the efficiency of conversion is affected by polymorphic variation in the cervid and human prion protein genes. In view of the similarity of reindeer, elk, and white-tailed deer in North America to reindeer, red deer, and roe deer, respectively, in Europe, a more comprehensive and thorough assessment of the zoonotic potential of CWD might be warranted.

snip...

Discussion

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

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

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

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

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



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


Acknowledgments

snip...see;
 



Molecular Barriers to Zoonotic Transmission of Prions 
 
Marcelo A. Barria, Aru Balachandran, Masanori Morita, Tetsuyuki Kitamoto, Rona Barron, Jean Manson, Richard Knight, James W. Ironside, and Mark W. Headcorresponding author 
 
snip... 
 
The conversion of human PrPC by CWD brain homogenate in PMCA reactions was less efficient when the amino acid at position 129 was valine rather than methionine. 
 
***Furthermore, the form of human PrPres produced in this in vitro assay when seeded with CWD, resembles that found in the most common human prion disease, namely sCJD of the MM1 subtype. 
 
snip... 
 
However, we can say with confidence that under the conditions used here, none of the animal isolates tested were as efficient as C-type BSE in converting human PrPC, which is reassuring. 
 
***Less reassuring is the finding that there is no absolute barrier to the conversion of human PrPC by CWD prions in a protocol using a single round of PMCA and an entirely human substrate prepared from the target organ of prion diseases, the brain. 


 

Prion 2017 
 
Conference Abstracts CWD 2017 PRION 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 
 
Subject: PRION 2017 CONFERENCE DECIPHERING NEURODEGENERATIVE DISORDERS VIDEO 
 
PRION 2017 
 
CONFERENCE DECIPHERING NEURODEGENERATIVE DISORDERS 
 
*** PRION 2017 CONFERENCE VIDEO 
 
 

TUESDAY, JUNE 13, 2017 
 
PRION 2017 CONFERENCE ABSTRACT 
 
First evidence of intracranial and peroral transmission of Chronic Wasting Disease (CWD) into Cynomolgus macaques: a work in progress 
 
 
 
Risk Advisory Opinion: Potential Human Health Risks from Chronic Wasting Disease CFIA, PHAC, HC (HPFB and FNIHB), INAC, Parks Canada, ECCC and AAFC 
 
http://chronic-wasting-disease.blogspot.com/2017/07/risk-advisory-opinion-potential-human.html


***> 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. <***

***> SEE;

***> These observations strongly suggest that the spectrum of human prion diseases may extend the current field restricted to the phenotypes associated to protease-resistant PrP, and may notably include spinal cord diseases. <***


Unexpected prion phenotypes in experimentally transfused animals: predictive models for humans? 

Emmanuel E. Comoy, Jacqueline Mikol & Jean-Philippe Deslys 

Pages 162-169 | Received 06 Jul 2018, Accepted 24 Jul 2018, Accepted author version posted online: 06 Aug 2018, Published online: 16 Aug 2018

ABSTRACT 

The recently reevaluated high prevalence of healthy carriers (1/2,000 in UK) of variant Creutzfeldt-Jakob Disease (v-CJD), whose blood might be infectious, suggests that the evolution of this prion disease might not be under full control as expected. 

After experimental transfusion of macaques and conventional mice with blood derived from v-CJD exposed (human and animal) individuals, we confirmed in these both models the transmissibility of v-CJD, but we also observed unexpected neurological syndromes transmissible by transfusion: despite their prion etiology confirmed through transmission experiments, these original cases would escape classical prion diagnosis, notably in the absence of detectable abnormal PrP with current techniques. 

It is noteworthy that macaques developed an original, yet undescribed myelopathic syndrome associating demyelination and pseudo-necrotic lesions of spinal cord, brainstem and optical tract without affecting encephalon, which is rather evocative of spinal cord disease than prion disease in human medicine. 

These observations strongly suggest that the spectrum of human prion diseases may extend the current field restricted to the phenotypes associated to protease-resistant PrP, and may notably include spinal cord diseases.

KEYWORDS: (5-10): prion, vCJD, macaque, mouse, spinal cord disease, myelopathy, transfusion, abnormal PrP, demyelination, spongiform change

This article refers to:

Additional information

Funding

The original laboratory work was funded by European Commission [Fifth Framework Programme, QLK1-CT-2002-01096], French Research Funding Agency (Agence Nationale de la Recherche, ANR) [ANR-10-BLAN-1330 01], Health Canada [4500216567] and MacoPharma.



WEDNESDAY, OCTOBER 17, 2018 

PRICE OF TSE PRION POKER GOES UP spectrum of human prion diseases may extend the current field and may notably include spinal cord diseases



ZOONOTIC, ZOONOSIS, CHRONIC WASTING DISEASE CWD TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY TSE PRION 

10. ZOONOTIC, ZOONOSIS, CHRONIC WASTING DISEASE CWD TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY TSE PRION AKA MAD DEER ELK DISEASE IN HUMANS, has it already happened, that should be the question... 

''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)

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

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

also, see; 

8. Even though human TSE‐exposure risk through consumption of game from European cervids can be assumed to be minor, if at all existing, no final conclusion can be drawn due to the overall lack of scientific data. In particular the US data do not clearly exclude the possibility of human (sporadic or familial) TSE development due to consumption of venison. The Working Group thus recognizes a potential risk to consumers if a TSE would be present in European cervids. It might be prudent considering appropriate measures to reduce such a risk, e.g. excluding tissues such as CNS and lymphoid tissues from the human food chain, which would greatly reduce any potential risk for consumers. However, it is stressed that currently, no data regarding a risk of TSE infections from cervid products are available. 

snip... 

The tissue distribution of infectivity in CWD‐infected cervids is now known to extend beyond CNS and lymphoid tissues. While the removal of these specific tissues from the food chain would reduce human dietary exposure to infectivity, exclusion from the food chain of the whole carcass of any infected animal would be required to eliminate human dietary exposure. 
https://efsa.onlinelibrary..wiley.com/doi/full/10.2903/j.efsa.2018.5132

zoonosis zoonotic cervid tse prion cwd to humans, preparing for the storm 

***An alternative to modeling the species barrier is the cell-free conversion assay which points to CWD as the animal prion disease with the greatest zoonotic potential, after (and very much less than) BSE.116*** 
https://www.tandfonline.com/doi/pdf/10.4161/pri.29237
 
To date there is no direct evidence that CWD has been or can be transmitted from animals to humans. 

However, initial findings from a laboratory research project funded by the Alberta Prion Research Institute (APRI) and Alberta Livestock Meat Agency (ALMA), and led by a Canadian Food Inspection Agency (CFIA) scientist indicate that CWD has been transmitted to cynomolgus macaques (the non-human primate species most closely related to humans that may be used in research), through both the intracranial and oral routes of exposure. 

Both infected brain and muscle tissues were found to transmit disease. 

Health Canada’s Health Products and Food Branch (HPFB) was asked to consider the impact of these findings on the Branch’s current position on CWD in health products and foods. 

Summary and Recommendation: 

snip...

Health Portfolio partners were recently made aware of initial findings from a research project led by a CFIA scientist that have demonstrated that cynomolgus macaques can be infected via intracranial exposure and oral gavage with CWD infected muscle. 

These findings suggest that CWD, under specific experimental conditions, has the potential to cross the human species barrier, including by enteral feeding of CWD infected muscle. 
https://www.thetyee.ca/Documents/2017/06/24/Risk-Advisory-Opinion-CWD-2017.pdf


*** WDA 2016 NEW YORK *** 

We found that CWD adapts to a new host more readily than BSE and that human PrP was unexpectedly prone to misfolding by CWD prions. 

In addition, we investigated the role of specific regions of the bovine, deer and human PrP protein in resistance to conversion by prions from another species. 

***We have concluded that the human protein has a region that confers unusual susceptibility to conversion by CWD prions. 

Student Presentations Session 2 

The species barriers and public health threat of CWD and BSE prions 

Ms. Kristen Davenport1, Dr. Davin Henderson1, Dr. Candace Mathiason1, Dr. Edward Hoover1 1Colorado State University 

Chronic wasting disease (CWD) is spreading rapidly through cervid populations in the USA. Bovine spongiform encephalopathy (BSE, mad cow disease) arose in the 1980s because cattle were fed recycled animal protein. 

These and other prion diseases are caused by abnormal folding of the normal prion protein (PrP) into a disease causing form (PrPd), which is pathogenic to nervous system cells and can cause subsequent PrP to misfold. CWD spreads among cervids very efficiently, but it has not yet infected humans. On the other hand, BSE was spread only when cattle consumed infected bovine or ovine tissue, but did infect humans and other species. 

The objective of this research is to understand the role of PrP structure in cross-species infection by CWD and BSE. To study the propensity of each species’ PrP to be induced to misfold by the presence of PrPd from verious species, we have used an in vitro system that permits detection of PrPd in real-time. 

We measured the conversion efficiency of various combinations of PrPd seeds and PrP substrate combinations. 

We observed the cross-species behavior of CWD and BSE, in addition to feline-adapted CWD and BSE. We found that CWD adapts to a new host more readily than BSE and that human PrP was unexpectedly prone to misfolding by CWD prions. In addition, we investigated the role of specific regions of the bovine, deer and human PrP protein in resistance to conversion by prions from another species. 

***We have concluded that the human protein has a region that confers unusual susceptibility to conversion by CWD prions. CWD is unique among prion diseases in its rapid spread in natural populations. BSE prions are essentially unaltered upon passage to a new species, while CWD adapts to the new species. This adaptation has consequences for surveillance of humans exposed to CWD. Wildlife Disease Risk Communication Research Contributes to Wildlife Trust Administration Exploring perceptions about chronic wasting disease risks among wildlife and agriculture professionals and stakeholders
http://www.wda2016.org/uploads/5/8/6/1/58613359/wda_2016_conference_proceedings_low_res.pdf
 

CDC CWD 2018 TRANSMISSION
https://www.cdc.gov/prions/cwd/transmission.html


TUESDAY, SEPTEMBER 12, 2017 

CDC Now Recommends Strongly consider having the deer or elk tested for CWD before you eat the meat 
http://chronic-wasting-disease.blogspot.com/2017/09/cdc-now-recommends-strongly-consider.html


SATURDAY, JANUARY 27, 2018 

CDC CHRONIC WASTING DISEASE CWD TSE PRION UPDATE REPORT USA JANUARY 2018
http://chronic-wasting-disease.blogspot.com/2018/01/cdc-chronic-wasting-disease-cwd-tse.html


Subject: CDC CHRONIC WASTING DISEASE CWD TSE PRION UPDATE REPORT USA JANUARY 2018

CHRONIC WASTING DISEASE CWD TSE PRION IS THE USA AND NORTH AMERICA'S MAD COW DISEASE. 

THE USDA INC ET AL WORKED VERY HARD CONCEALING BSE TSE PRION IN CATTLE. they almost succeeded $$$

BUT CWD TSE PRION IN CERVIDS IS A DIFFERENT BEAST, THE COVER UP THERE, USDA INC COULD NOT CONTAIN.

SPORADIC CJD IS 85%+ OF ALL HUMAN TSE PRION DISEASE.

SPORADIC CJD HAS NOW BEEN LINKED TO TYPICAL AND ATYPICAL BSE, SCRAPIE, AND CWD.

SPORADIC/SPONTANEOUS TSE HAS NEVER BEEN PROVEN.

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


CDC CWD TSE PRION UPDATE USA JANUARY 2018

As of January 2018, CWD in free-ranging deer, elk and/or moose has been reported in at least 22 states in the continental United States, as well as two provinces in Canada. In addition, CWD has been reported in reindeer and moose in Norway, and a small number of imported cases have been reported in South Korea. The disease has also been found in farmed deer and elk. CWD was first identified in captive deer in the late 1960s in Colorado and in wild deer in 1981. By the 1990s, it had been reported in surrounding areas in northern Colorado and southern Wyoming. Since 2000, the area known to be affected by CWD in free-ranging animals has increased to at least 22 states, including states in the Midwest, Southwest, and limited areas on the East Coast.. It is possible that CWD may also occur in other states without strong animal surveillance systems, but that cases haven’t been detected yet. Once CWD is established in an area, the risk can remain for a long time in the environment. The affected areas are likely to continue to expand. Nationwide, the overall occurrence of CWD in free-ranging deer and elk is relatively low. However, in several locations where the disease is established, infection rates may exceed 10 percent (1 in 10), and localized infection rates of more than 25 percent (1 in 4) have been reported. The infection rates among some captive deer can be much higher, with a rate of 79% (nearly 4 in 5) reported from at least one captive herd. As of January 2018, there were 186 counties in 22 states with reported CWD in free-ranging cervids... 

Chronic Wasting Disease Among Free-Ranging Cervids by County, United States, January 2018 

snip.... 
https://www.cdc.gov/prions/cwd/occurrence.html


*** 2017-2018 CWD TSE Prion UPDATE
https://www.cdc.gov/prions/cwd/occurrence.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


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
http://www.fsis.usda.gov/OPPDE/Comments/03-025IFA/03-025IFA-2.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


*** 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 (216-119-163-189.ipset45.wt.net)

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


> 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


SEE; Travel History, Hunting, and Venison Consumption Related to Prion Disease Exposure, 2006-2007 FoodNet Population Survey

Monday, May 23, 2011

CDC Assesses Potential Human Exposure to Prion Diseases Travel Warning

Public release date: 23-May-2011

Contact: Francesca Costanzo adajmedia@elsevier.com 215-239-3249 Elsevier Health Sciences

CDC assesses potential human exposure to prion diseases Study results reported in the Journal of the American Dietetic Association Philadelphia, PA, May 23, 2011 – Researchers from the Centers for Disease Control and Prevention (CDC) have examined the potential for human exposure to prion diseases, looking at hunting, venison consumption, and travel to areas in which prion diseases have been reported in animals. Three prion diseases in particular – bovine spongiform encephalopathy (BSE or “Mad Cow Disease”), variant Creutzfeldt-Jakob disease (vCJD), and chronic wasting disease (CWD) – were specified in the investigation. The results of this investigation are published in the June issue of the Journal of the American Dietetic Association.

“While prion diseases are rare, they are generally fatal for anyone who becomes infected. More than anything else, the results of this study support the need for continued surveillance of prion diseases,” commented lead investigator Joseph Y. Abrams, MPH, National Center for Emerging and Zoonotic Infectious Diseases, CDC, Atlanta.”But it’s also important that people know the facts about these diseases, especially since this study shows that a good number of people have participated in activities that may expose them to infection-causing agents.”

Although rare, human prion diseases such as CJD may be related to BSE. Prion (proteinaceous infectious particles) diseases are a group of rare brain diseases that affect humans and animals. When a person gets a prion disease, brain function is impaired. This causes memory and personality changes, dementia, and problems with movement. All of these worsen over time. These diseases are invariably fatal. Since these diseases may take years to manifest, knowing the extent of human exposure to possible prion diseases could become important in the event of an outbreak.

CDC investigators evaluated the results of the 2006-2007 population survey conducted by the Foodborne Diseases Active Surveillance Network (FoodNet). This survey collects information on food consumption practices, health outcomes, and demographic characteristics of residents of the participating Emerging Infections Program sites. The survey was conducted in Connecticut, Georgia, Maryland, Minnesota, New Mexico, Oregon, and Tennessee, as well as five counties in the San Francisco Bay area, seven counties in the Greater Denver area, and 34 counties in western and northeastern New York.

Survey participants were asked about behaviors that could be associated with exposure to the agents causing BSE and CWD, including travel to the nine countries considered to be BSE-endemic (United Kingdom, Republic of Ireland, France, Portugal, Switzerland, Italy, the Netherlands, Germany, Spain) and the cumulative length of stay in each of those countries. Respondents were asked if they ever had hunted for deer or elk, and if that hunting had taken place in areas considered to be CWD-endemic (northeastern Colorado, southeastern Wyoming or southwestern Nebraska). They were also asked if they had ever consumed venison, the frequency of consumption, and whether the meat came from the wild.

The proportion of survey respondents who reported travel to at least one of the nine BSE endemic countries since 1980 was 29.5%. Travel to the United Kingdom was reported by 19.4% of respondents, higher than to any other BSE-endemic country. Among those who traveled, the median duration of travel to the United Kingdom (14 days) was longer than that of any other BSE-endemic country. Travelers to the UK were more likely to have spent at least 30 days in the country (24.9%) compared to travelers to any other BSE endemic country. The prevalence and extent of travel to the UK indicate that health concerns in the UK may also become issues for US residents.

The proportion of survey respondents reporting having hunted for deer or elk was 18.5% and 1.2% reported having hunted for deer or elk in CWD-endemic areas. Venison consumption was reported by 67.4% of FoodNet respondents, and 88.6% of those reporting venison consumption had obtained all of their meat from the wild. These findings reinforce the importance of CWD surveillance and control programs for wild deer and elk to reduce human exposure to the CWD agent. Hunters in CWD-endemic areas are advised to take simple precautions such as: avoiding consuming meat from sickly deer or elk, avoiding consuming brain or spinal cord tissues, minimizing the handling of brain and spinal cord tissues, and wearing gloves when field-dressing carcasses.

According to Abrams, “The 2006-2007 FoodNet population survey provides useful information should foodborne prion infection become an increasing public health concern in the future. The data presented describe the prevalence of important behaviors and their associations with demographic characteristics. Surveillance of BSE, CWD, and human prion diseases are critical aspects of addressing the burden of these diseases in animal populations and how that may relate to human health.”

###

The article is “Travel history, hunting, and venison consumption related to prion disease exposure, 2006-2007 FoodNet population survey” by Joseph Y. Abrams, MPH; Ryan A. Maddox, MPH; Alexis R Harvey, MPH; Lawrence B. Schonberger, MD; and Ermias D. Belay, MD. It appears in the Journal of the American Dietetic Association, Volume 111, Issue 6 (June 2011) published by Elsevier.

In an accompanying podcast CDC’s Joseph Y. Abrams discusses travel, hunting, and eating venison in relation to prion diseases. It is available at http://adajournal.org/content/podcast.
http://www.eurekalert.org/pub_releases/2011-05/ehs-cap051811.php


Thursday, May 26, 2011

Travel History, Hunting, and Venison Consumption Related to Prion Disease Exposure, 2006-2007 FoodNet Population Survey

Journal of the American Dietetic Association Volume 111, Issue 6 , Pages 858-863, June 2011.

Travel History, Hunting, and Venison Consumption Related to Prion Disease Exposure, 2006-2007 FoodNet Population Survey

Joseph Y. Abrams, MPH, Ryan A. Maddox, MPH , Alexis R. Harvey, MPH , Lawrence B. Schonberger, MD , Ermias D. Belay, MD

Accepted 15 November 2010. Abstract Full Text PDF References .

Abstract

The transmission of bovine spongiform encephalopathy (BSE) to human beings and the spread of chronic wasting disease (CWD) among cervids have prompted concerns about zoonotic transmission of prion diseases. Travel to the United Kingdom and other European countries, hunting for deer or elk, and venison consumption could result in the exposure of US residents to the agents that cause BSE and CWD. The Foodborne Diseases Active Surveillance Network 2006-2007 population survey was used to assess the prevalence of these behaviors among residents of 10 catchment areas across the United States. Of 17,372 survey respondents, 19.4% reported travel to the United Kingdom since 1980, and 29.5% reported travel to any of the nine European countries considered to be BSE-endemic since 1980. The proportion of respondents who had ever hunted deer or elk was 18.5%, and 1.2% had hunted deer or elk in a CWD–endemic area. More than two thirds (67.4%) reported having ever eaten deer or elk meat. Respondents who traveled spent more time in the United Kingdom (median 14 days) than in any other BSE-endemic country. Of the 11,635 respondents who had consumed venison, 59.8% ate venison at most one to two times during their year of highest consumption, and 88.6% had obtained all of their meat from the wild. The survey results were useful in determining the prevalence and frequency of behaviors that could be important factors for foodborne prion transmission.
http://www.adajournal.org/article/S0002-8223(11)00278-1/abstract


PLUS, THE CDC DID NOT PUT THIS WARNING OUT FOR THE WELL BEING OF THE DEER AND ELK ; 

Thursday, May 26, 2011

Travel History, Hunting, and Venison Consumption Related to Prion Disease Exposure, 2006-2007 FoodNet Population Survey

Journal of the American Dietetic Association Volume 111, Issue 6 , Pages 858-863, June 2011.
http://transmissiblespongiformencephalopathy.blogspot.com/2011/05/travel-history-hunting-and-venison.html


NOR IS THE FDA recalling this CWD positive elk meat for the well being of the dead elk ;

Wednesday, March 18, 2009

Noah's Ark Holding, LLC, Dawson, MN RECALL Elk products contain meat derived from an elk confirmed to have CWD NV, CA, TX, CO, NY, UT, FL, OK RECALLS AND FIELD CORRECTIONS: FOODS CLASS II
http://chronic-wasting-disease.blogspot.com/2009/03/noahs-ark-holding-llc-dawson-mn-recall.html

 Transmissible Spongiform Encephalopathies

Spongiform Encephalopathy in Captive Wild ZOO BSE INQUIRY
https://web.archive.org/web/20090506001201/http://www.bseinquiry.gov.uk/files/mb/m09a/tab03.pdf


BSE INQUIRY

CJD9/10022

October 1994

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

BerksWell Coventry CV7 7BZ

Dear Mr Elmhirst,

CREUTZFELDT-JAKOB DISEASE (CJD) SURVEILLANCE UNIT REPORT

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

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

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

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

I believe that a further statement about the report, or indeed statistical links between CJD and consumption of venison, would increase, and quite possibly give damaging credence, to the whole issue. From the low key media reports of which I am aware it seems unlikely that venison consumption will suffer adversely, if at all.
http://web.archive.org/web/20030511010117/http://www.bseinquiry.gov.uk/files/yb/1994/10/00003001.pdf


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

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

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

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

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

snip...

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

snip...

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

snip...

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

snip...see full report ;

https://web.archive.org/web/20170126073306/http://collections..europarchive..org/tna/20090505194948/http://bseinquiry.gov.uk/files/yb/1994/08/00004001.pdf


THURSDAY, OCTOBER 04, 2018 

***> Cervid to human prion transmission 5R01NS088604-04 Update




ALSO, I FIND THIS VERY DISTURBING...SEE;


***> Prion 2018 P74 High Prevalence of CWD prions in male reproductive samples 

Carlos Kramm (1,2), Ruben Gomez-Gutierrez (1,3), Tracy Nichols (4), Claudio Soto (1) and Rodrigo Morales (1) 



READING OVER THE PRION 2018 ABSTRACT BOOK, LOOKS LIKE THEY FOUND THAT Protein Misfolding Cyclic Amplification PMCA results showed positive CWD prion detection in testes, epididymis and seminal fluid samples. seems also the scientists are worried about any potential mechanisms of CWD spreading and they want to decrease putative interindividual transmission associated to insemination using CWD contaminated specimens, if that might occur under natural conditions. i have been concerned about this for some time with BSE super-ovulation and since;

 PrPSc detection and infectivity in semen from scrapie-infected sheep




PITUITARY EXTRACT

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








MANAGEMENT IN CONFIDENCE

CERTIFIED BSE-FREE HERDS FOR SOURCE OF MATERIAL FOR BIOLOGICAL PRODUCTS




Singeltary ***> U.S.A. 50 STATE BSE MAD COW CONFERENCE CALL Jan. 9, 2001




HAVE YOU BEEN THUNDERSTRUCK? 

SUNDAY, AUGUST 02, 2015 

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

Court papers state that in February 2007, Favero acquired 184 straws of whitetail deer semen valued at about $92,000 from a buck named “Diablo'” that he knew had been illegally taken out of Texas, and again in January 2008 took another 110 straws of semen from a buck named “Thunderstruck.” (Read more in the court paper posted at the bottom of this entry.)



SUNDAY, AUGUST 19, 2018 

Texas Deer Farms, Growing Freakish Antlers, and CWD TSE Prion aka mad deer disease



WEDNESDAY, OCTOBER 03, 2018 

Texas Reports 13 more cases of Chronic Wasting Disease CWD TSE Prion in Breeder Deer state total jumps to 130 Confirmed to date



SATURDAY, NOVEMBER 10, 2018 

Pennsylvania Thirty-Eight Deer Test Positive for Chronic Wasting Disease on Fulton and Bedford County Deer Farms



FRIDAY, NOVEMBER 09, 2018 

Minnesota CWD TSE Prion detected four harvested samples from farmed deer quarantined farm Crow Wing County



FRIDAY, NOVEMBER 09, 2018 

Minnesota Chronic Wasting Disease CWD TSE Prion Captive Cervid Farming SSS testing policy



THURSDAY, OCTOBER 04, 2018 

Cervid to human prion transmission 5R01NS088604-04 Update



SATURDAY, NOVEMBER 10, 2018 

cwd, bse, scrapie, cjd, tse prion updated November 10 2018



THURSDAY, OCTOBER 25, 2018 

***> Norway New additional requirements for imports of hay and straw for animal feed from countries outside the EEA due to CWD TSE Prion




FRIDAY, MARCH 30, 2018 

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

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

Attachments (1) Docket No. APHIS-2018-0011 Chronic Wasting Disease Herd Certification Program Standards Singeltary View Attachment:View as format pdf 



https://www.regulations.gov/docketBrowser?rpp=25&so=DESC&sb=commentDueDate&po=0&dct=PS&D=APHIS-2018-0011



Friday, December 14, 2012

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

snip.....

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

Animals considered at high risk for CWD include:

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

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

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

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

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

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

snip.....

36% in 2007 (Almberg et al., 2011). In such areas, population declines of deer of up to 30 to 50% have been observed (Almberg et al., 2011). In areas of Colorado, the prevalence can be as high as 30% (EFSA, 2011).

The clinical signs of CWD in affected adults are weight loss and behavioural changes that can span weeks or months (Williams, 2005). In addition, signs might include excessive salivation, behavioural alterations including a fixed stare and changes in interaction with other animals in the herd, and an altered stance (Williams, 2005). These signs are indistinguishable from cervids experimentally infected with bovine spongiform encephalopathy (BSE).

Given this, if CWD was to be introduced into countries with BSE such as GB, for example, infected deer populations would need to be tested to differentiate if they were infected with CWD or BSE to minimise the risk of BSE entering the human food-chain via affected venison.

snip.....

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

snip.....

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

snip.....

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

snip.....

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

snip.....



TUESDAY, APRIL 18, 2017 

*** EXTREME USA FDA PART 589 TSE PRION FEED LOOP HOLE STILL EXIST, AND PRICE OF POKER GOES UP ***



TUESDAY, JANUARY 17, 2017 

FDA PART 589 -- SUBSTANCES PROHIBITED FROM USE IN ANIMAL FOOD OR FEEDVIOLATIONS OFFICIAL ACTION INDICATED OAI UPDATE 2016 to 2017 BSE TSE PRION



THIS April, 4, 2017 

violation of the mad cow 21 CFR 589.2000 OAI is very serious for the great state of Michigan, some 20 years post FDA mad cow feed of August 1997. if would most likely take a FOIA request and a decade of wrangling to find out more. 

TUESDAY, JANUARY 17, 2017

FDA PART 589 -- SUBSTANCES PROHIBITED FROM USE IN ANIMAL FOOD OR FEEDVIOLATIONS OFFICIAL ACTION INDICATED OAI UPDATE 2016 to 2017 BSE TSE PRION

FDA PART 589 -- SUBSTANCES PROHIBITED FROM USE IN ANIMAL FOOD OR FEEDVIOLATIONS OFFICIAL ACTION INDICATED OAI UPDATE 2016 to 2017 BSE TSE PRION 

I would kindly like to comment on this FDA BSE/Ruminant Feed Inspections Firms Inventory (excel format)4 format, for reporting these breaches of BSE TSE prion protocols, from the extensive mad cow feed ban warning letters the fda use to put out for each violations. simply put, this excel format sucks, and the FDA et al intentionally made it this difficult to follow the usda fda mad cow follies. this is an intentional format to make it as difficult as possible to follow these breaches of the mad cow TSE prion safety feed protocols. to have absolutely no chronological or numerical order, and to format such violations in a way that they are almost impossible to find, says a lot about just how far the FDA and our fine federal friends will go through to hide these continued violations of the BSE TSE prion mad cow feed ban, and any breaches of protocols there from. once again, the wolf guarding the henhouse $$$

NAI = NO ACTION INDICATED

OAI = OFFICIAL ACTION INDICATED

VAI = VOLUNTARY ACTION INDICATED

RTS = REFERRED TO STATE

OAI (Official Action Indicated) when inspectors find significant objectionable conditions or practices and believe that regulatory sanctions are warranted to address the establishment’s lack of compliance with the regulation. An example of an OAI classification would be findings of manufacturing procedures insufficient to ensure that ruminant feed is not contaminated with prohibited material. Inspectors will promptly re-inspect facilities classified OAI after regulatory sanctions have been applied to determine whether the corrective actions are adequate to address the objectionable conditions. 

2016




ONE more thing, please remember, the label does not have to say ''deer ration'' for cervid to be pumped up with. you can get the same ''high protein'' from many sources of high protein feed for animals other than cattle, and feed them to cervid...



Saturday, August 29, 2009

FOIA REQUEST FEED RECALL 2009 Product may have contained prohibited materials Bulk Whole Barley, Recall # V-256-2009




Friday, September 4, 2009

FOIA REQUEST ON FEED RECALL PRODUCT 429,128 lbs. feed for ruminant animals may have been contaminated with prohibited material Recall # V-258-2009




WEDNESDAY, JULY 11, 2018 

CONFIDENTIAL IN CONFIDENCE SPONGIFORM ENCEPHALOPATHY OF PIGS FDA EMERGENCY REQUEST FOR RULE CHANGE USA Section 21 C.F.R. 589.2000

http://transmissiblespongiformencephalopathy.blogspot.com/2018/07/confidential-in-confidence-spongiform.html



TUESDAY, JULY 10, 2018
 
CONFIDENTIAL IN CONFIDENCE SPONGIFORM ENCEPHALOPATHY OF PIGS
 
*** ''but feeding of other ruminant protein, including scrapie-infected sheep, can continue to pigs.''
 
CONFIDENTIAL SPONGIFORM ENCEPHALOPATHY OF PIGS
 
http://madporcinedisease.blogspot.com/2018/07/confidential-in-confidence-spongiform.html



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

Juan Maria Torres a, Olivier Andreoletti b, J uan-Carlos Espinosa a. Vincent Beringue c. Patricia Aguilar a,

Natalia Fernandez-Borges a. and Alba Marin-Moreno a

"Centro de Investigacion en Sanidad Animal ( CISA-INIA ). Valdeolmos, Madrid. Spain; b UMR INRA -ENVT 1225 Interactions Holes Agents Pathogenes. ENVT. Toulouse. France: "UR892. Virologie lmmunologie MolécuIaires, Jouy-en-Josas. France

Dietary exposure to bovine spongiform encephalopathy (BSE) contaminated bovine tissues is considered as the origin of variant Creutzfeldt Jakob (vCJD) disease in human. To date, BSE agent is the only recognized zoonotic prion.. Despite the variety of Transmissible Spongiform Encephalopathy (TSE) agents that have been circulating for centuries in farmed ruminants there is no apparent epidemiological link between exposure to ruminant products and the occurrence of other form of TSE in human like sporadic Creutzfeldt Jakob Disease (sCJD). However, the zoonotic potential of the diversity of circulating TSE agents has never been systematically assessed. The major issue in experimental assessment of TSEs zoonotic potential lies in the modeling of the ‘species barrier‘, the biological phenomenon that limits TSE agents’ propagation from a species to another. In the last decade, mice genetically engineered to express normal forms of the human prion protein has proved essential in studying human prions pathogenesis and modeling the capacity of TSEs to cross the human species barrier.

To assess the zoonotic potential of prions circulating in farmed ruminants, we study their transmission ability in transgenic mice expressing human PrPC (HuPrP-Tg). Two lines of mice expressing different forms of the human PrPC (129Met or 129Val) are used to determine the role of the Met129Val dimorphism in susceptibility/resistance to the different agents.

These transmission experiments confirm the ability of BSE prions to propagate in 129M- HuPrP-Tg mice and demonstrate that Met129 homozygotes may be susceptible to BSE in sheep or goat to a greater degree than the BSE agent in cattle and that these agents can convey molecular properties and neuropathological indistinguishable from vCJD. However homozygous 129V mice are resistant to all tested BSE derived prions independently of the originating species suggesting a higher transmission barrier for 129V-PrP variant.

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

why do we not want to do TSE transmission studies on chimpanzees $

5. A positive result from a chimpanzee challenged severly would likely create alarm in some circles even if the result could not be interpreted for man. I have a view that all these agents could be transmitted provided a large enough dose by appropriate routes was given and the animals kept long enough. Until the mechanisms of the species barrier are more clearly understood it might be best to retain that hypothesis.

snip...

R. BRADLEY
https://web.archive.org/web/20170126051158/http://collections.europarchive.org/tna/20080102222950/http://www.bseinquiry.gov.uk/files/yb/1990/09/23001001.pdf

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


***> 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. <***

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

Emmanuel E. Comoy, Jacqueline Mikol, Sophie Luccantoni-Freire, Evelyne Correia, Nathalie Lescoutra-Etchegaray, Valérie Durand, Capucine Dehen, Olivier Andreoletti, Cristina Casalone, Juergen A. Richt, Justin J. Greenlee, Thierry Baron, Sylvie L. Benestad, Paul Brown & Jean-Philippe Deslys Scientific Reports volume 5, Article number: 11573 (2015) | Download Citation

Abstract 

Classical bovine spongiform encephalopathy (c-BSE) is the only animal prion disease reputed to be zoonotic, causing variant Creutzfeldt-Jakob disease (vCJD) in humans and having guided protective measures for animal and human health against animal prion diseases. Recently, partial transmissions to humanized mice showed that the zoonotic potential of scrapie might be similar to c-BSE. We here report the direct transmission of a natural classical scrapie isolate to cynomolgus macaque, a highly relevant model for human prion diseases, after a 10-year silent incubation period, with features similar to those reported for human cases of sporadic CJD. Scrapie is thus actually transmissible to primates with incubation periods compatible with their life expectancy, although fourfold longer than BSE. Long-term experimental transmission studies are necessary to better assess the zoonotic potential of other prion diseases with high prevalence, notably Chronic Wasting Disease of deer and elk and atypical/Nor98 scrapie.

SNIP...

Discussion We describe the transmission of spongiform encephalopathy in a non-human primate inoculated 10 years earlier with a strain of sheep c-scrapie. Because of this extended incubation period in a facility in which other prion diseases are under study, we are obliged to consider two alternative possibilities that might explain its occurrence. We first considered the possibility of a sporadic origin (like CJD in humans). Such an event is extremely improbable because the inoculated animal was 14 years old when the clinical signs appeared, i.e. about 40% through the expected natural lifetime of this species, compared to a peak age incidence of 60–65 years in human sporadic CJD, or about 80% through their expected lifetimes. 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.

The second possibility is a laboratory cross-contamination. Three facts make this possibility equally unlikely. First, handling of specimens in our laboratory is performed with fastidious attention to the avoidance of any such cross-contamination. Second, no laboratory cross-contamination has ever been documented in other primate laboratories, including the NIH, even between infected and uninfected animals housed in the same or adjacent cages with daily intimate contact (P. Brown, personal communication). Third, the cerebral lesion profile is different from all the other prion diseases we have studied in this model19, with a correlation between cerebellar lesions (massive spongiform change of Purkinje cells, intense PrPres staining and reactive gliosis26) and ataxia. The iron deposits present in the globus pallidus are a non specific finding that have been reported previously in neurodegenerative diseases and aging27. Conversely, the thalamic lesion was reminiscent of a metabolic disease due to thiamine deficiency28 but blood thiamine levels were within normal limits (data not shown). The preferential distribution of spongiform change in cortex associated with a limited distribution in the brainstem is reminiscent of the lesion profile in MM2c and VV1 sCJD patients29, but interspecies comparison of lesion profiles should be interpreted with caution. It is of note that the same classical scrapie isolate induced TSE in C57Bl/6 mice with similar incubation periods and lesional profiles as a sample derived from a MM1 sCJD patient30.

We are therefore confident that the illness in this cynomolgus macaque represents a true transmission of a sheep c-scrapie isolate directly to an old-world monkey, which taxonomically resides in the primate subdivision (parvorder of catarrhini) that includes humans. With an homology of its PrP protein with humans of 96.4%31, cynomolgus macaque constitutes a highly relevant model for assessing zoonotic risk of prion diseases. Since our initial aim was to show the absence of transmission of scrapie to macaques in the worst-case scenario, we obtained materials from a flock of naturally-infected sheep, affecting animals with different genotypes32. This c-scrapie isolate exhibited complete transmission in ARQ/ARQ sheep (332 ± 56 days) and Tg338 transgenic mice expressing ovine VRQ/VRQ prion protein (220 ± 5 days) (O. Andreoletti, personal communication). From the standpoint of zoonotic risk, it is important to note that sheep with c-scrapie (including the isolate used in our study) have demonstrable infectivity throughout their lymphoreticular system early in the incubation period of the disease (3 months-old for all the lymphoid organs, and as early as 2 months-old in gut-associated lymph nodes)33. In addition, scrapie infectivity has been identified in blood34, milk35 and skeletal muscle36 from asymptomatic but scrapie infected small ruminants which implies a potential dietary exposure for consumers.

Two earlier studies have reported the occurrence of clinical TSE in cynomolgus macaques after exposures to scrapie isolates. In the first study, the “Compton” scrapie isolate (derived from an English sheep) and serially propagated for 9 passages in goats did not transmit TSE in cynomolgus macaque, rhesus macaque or chimpanzee within 7 years following intracerebral challenge1; conversely, after 8 supplementary passages in conventional mice, this “Compton” isolate induced TSE in a cynomolgus macaque 5 years after intracerebral challenge, but rhesus macaques and chimpanzee remained asymptomatic 8.5 years post-exposure8. However, multiple successive passages that are classically used to select laboratory-adapted prion strains can significantly modify the initial properties of a scrapie isolate, thus questioning the relevance of zoonotic potential for the initial sheep-derived isolate. The same isolate had also induced disease into squirrel monkeys (new-world monkey)9. A second historical observation reported that a cynomolgus macaque developed TSE 6 years post-inoculation with brain homogenate from a scrapie-infected Suffolk ewe (derived from USA), whereas a rhesus macaque and a chimpanzee exposed to the same inoculum remained healthy 9 years post-exposure1. This inoculum also induced TSE in squirrel monkeys after 4 passages in mice. Other scrapie transmission attempts in macaque failed but had more shorter periods of observation in comparison to the current study. Further, it is possible that there are differences in the zoonotic potential of different scrapie strains.

The most striking observation in our study is the extended incubation period of scrapie in the macaque model, which has several implications. Firstly, our observations constitute experimental evidence in favor of the zoonotic potential of c-scrapie, at least for this isolate that has been extensively studied32,33,34,35,36. The cross-species zoonotic ability of this isolate should be confirmed by performing duplicate intracerebral exposures and assessing the transmissibility by the oral route (a successful transmission of prion strains through the intracerebral route may not necessarily indicate the potential for oral transmission37). However, such confirmatory experiments may require more than one decade, which is hardly compatible with current general management and support of scientific projects; thus this study should be rather considered as a case report.

Secondly, transmission of c-BSE to primates occurred within 8 years post exposure for the lowest doses able to transmit the disease (the survival period after inoculation is inversely proportional to the initial amount of infectious inoculum). The occurrence of scrapie 10 years after exposure to a high dose (25 mg) of scrapie-infected sheep brain suggests that the macaque has a higher species barrier for sheep c-scrapie than c-BSE, although it is notable that previous studies based on in vitro conversion of PrP suggested that BSE and scrapie prions would have a similar conversion potential for human PrP38.

Thirdly, prion diseases typically have longer incubation periods after oral exposure than after intracerebral inoculations: since humans can develop Kuru 47 years after oral exposure39, an incubation time of several decades after oral exposure to scrapie would therefore be expected, leading the disease to occur in older adults, i.e. the peak age for cases considered to be sporadic disease, and making a distinction between scrapie-associated and truly sporadic disease extremely difficult to appreciate.

Fourthly, epidemiologic evidence is necessary to confirm the zoonotic potential of an animal disease suggested by experimental studies. A relatively short incubation period and a peculiar epidemiological situation (e.g., all the first vCJD cases occurring in the country with the most important ongoing c-BSE epizootic) led to a high degree of suspicion that c-BSE was the cause of vCJD. Sporadic CJD are considered spontaneous diseases with an almost stable and constant worldwide prevalence (0.5–2 cases per million inhabitants per year), and previous epidemiological studies were unable to draw a link between sCJD and classical scrapie6,7,40,41, even though external causes were hypothesized to explain the occurrence of some sCJD clusters42,43,44. However, extended incubation periods exceeding several decades would impair the predictive values of epidemiological surveillance for prion diseases, already weakened by a limited prevalence of prion diseases and the multiplicity of isolates gathered under the phenotypes of “scrapie” and “sporadic CJD”.

Fifthly, considering this 10 year-long incubation period, together with both laboratory and epidemiological evidence of decade or longer intervals between infection and clinical onset of disease, no premature conclusions should be drawn from negative transmission studies in cynomolgus macaques with less than a decade of observation, as in the aforementioned historical transmission studies of scrapie to primates1,8,9. Our observations and those of others45,46 to date are unable to provide definitive evidence regarding the zoonotic potential of CWD, atypical/Nor98 scrapie or H-type BSE. The extended incubation period of the scrapie-affected macaque in the current study also underscores the limitations of rodent models expressing human PrP for assessing the zoonotic potential of some prion diseases since their lifespan remains limited to approximately two years21,47,48. This point is illustrated by the fact that the recently reported transmission of scrapie to humanized mice was not associated with clinical signs for up to 750 days and occurred in an extreme minority of mice with only a marginal increase in attack rate upon second passage13. The low attack rate in these studies is certainly linked to the limited lifespan of mice compared to the very long periods of observation necessary to demonstrate the development of scrapie. Alternatively, one could estimate that a successful second passage is the result of strain adaptation to the species barrier, thus poorly relevant of the real zoonotic potential of the original scrapie isolate of sheep origin49. The development of scrapie in this primate after an incubation period compatible with its lifespan complements the study conducted in transgenic (humanized) mice; taken together these studies suggest that some isolates of sheep scrapie can promote misfolding of the human prion protein and that scrapie can develop within the lifespan of some primate species.

In addition to previous studies on scrapie transmission to primate1,8,9 and the recently published study on transgenic humanized mice13, our results constitute new evidence for recommending that the potential risk of scrapie for human health should not be dismissed. Indeed, human PrP transgenic mice and primates are the most relevant models for investigating the human transmission barrier. To what extent such models are informative for measuring the zoonotic potential of an animal TSE under field exposure conditions is unknown. During the past decades, many protective measures have been successfully implemented to protect cattle from the spread of c-BSE, and some of these measures have been extended to sheep and goats to protect from scrapie according to the principle of precaution. Since cases of c-BSE have greatly reduced in number, those protective measures are currently being challenged and relaxed in the absence of other known zoonotic animal prion disease. We recommend that risk managers should be aware of the long term potential risk to human health of at least certain scrapie isolates, notably for lymphotropic strains like the classical scrapie strain used in the current study. Relatively high amounts of infectivity in peripheral lymphoid organs in animals infected with these strains could lead to contamination of food products produced for human consumption. Efforts should also be maintained to further assess the zoonotic potential of other animal prion strains in long-term studies, notably lymphotropic strains with high prevalence like CWD, which is spreading across North America, and atypical/Nor98 scrapie (Nor98)50 that was first detected in the past two decades and now represents approximately half of all reported cases of prion diseases in small ruminants worldwide, including territories previously considered as scrapie free.. 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.


Singeltary on Scrapie and human transmission way back, see;



***> CONGRESSIONAL ABSTRACTS PRION CONFERENCE 2018

P69 Experimental transmission of CWD from white-tailed deer to co-housed reindeer 

Mitchell G (1), Walther I (1), Staskevicius A (1), Soutyrine A (1), Balachandran A (1) 

(1) National & OIE Reference Laboratory for Scrapie and CWD, Canadian Food Inspection Agency, Ottawa, Ontario, Canada. 

Chronic wasting disease (CWD) continues to be detected in wild and farmed cervid populations of North America, affecting predominantly white-tailed deer, mule deer and elk. Extensive herds of wild caribou exist in northern regions of Canada, although surveillance has not detected the presence of CWD in this population. Oral experimental transmission has demonstrated that reindeer, a species closely related to caribou, are susceptible to CWD. Recently, CWD was detected for the first time in Europe, in wild Norwegian reindeer, advancing the possibility that caribou in North America could also become infected. Given the potential overlap in habitat between wild CWD-infected cervids and wild caribou herds in Canada, we sought to investigate the horizontal transmissibility of CWD from white-tailed deer to reindeer. 

Two white-tailed deer were orally inoculated with a brain homogenate prepared from a farmed Canadian white-tailed deer previously diagnosed with CWD. Two reindeer, with no history of exposure to CWD, were housed in the same enclosure as the white-tailed deer, 3.5 months after the deer were orally inoculated. The white-tailed deer developed clinical signs consistent with CWD beginning at 15.2 and 21 months post-inoculation (mpi), and were euthanized at 18.7 and 23.1 mpi, respectively. Confirmatory testing by immunohistochemistry (IHC) and western blot demonstrated widespread aggregates of pathological prion protein (PrPCWD) in the central nervous system and lymphoid tissues of both inoculated white-tailed deer. Both reindeer were subjected to recto-anal mucosal associated lymphoid tissue (RAMALT) biopsy at 20 months post-exposure (mpe) to the white-tailed deer. The biopsy from one reindeer contained PrPCWD confirmed by IHC. This reindeer displayed only subtle clinical evidence of disease prior to a rapid decline in condition requiring euthanasia at 22.5 mpe. Analysis of tissues from this reindeer by IHC revealed widespread PrPCWD deposition, predominantly in central nervous system and lymphoreticular tissues. Western blot molecular profiles were similar between both orally inoculated white-tailed deer and the CWD positive reindeer. Despite sharing the same enclosure, the other reindeer was RAMALT negative at 20 mpe, and PrPCWD was not detected in brainstem and lymphoid tissues following necropsy at 35 mpe. Sequencing of the prion protein gene from both reindeer revealed differences at several codons, which may have influenced susceptibility to infection. 

Natural transmission of CWD occurs relatively efficiently amongst cervids, supporting the expanding geographic distribution of disease and the potential for transmission to previously naive populations. The efficient horizontal transmission of CWD from white-tailed deer to reindeer observed here highlights the potential for reindeer to become infected if exposed to other cervids or environments infected with CWD. 




TITLE: PATHOLOGICAL FEATURES OF CHRONIC WASTING DISEASE IN REINDEER AND DEMONSTRATION OF HORIZONTAL TRANSMISSION 



 *** DECEMBER 2016 CDC EMERGING INFECTIOUS DISEASE JOURNAL CWD HORIZONTAL TRANSMISSION 



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

*** Nine of these recurrences occurred 14–21 years after culling

Gudmundur Georgsson,1 Sigurdur Sigurdarson2 and Paul Brown3

Correspondence Gudmundur Georgsson ggeorgs@hi.is

1 Institute for Experimental Pathology, University of Iceland, Keldur v/vesturlandsveg, IS-112 Reykjavı´k, Iceland

2 Laboratory of the Chief Veterinary Officer, Keldur, Iceland

3 Bethesda, Maryland, USA Received 7 March 2006 Accepted 6 August 2006

In 1978, a rigorous programme was implemented to stop the spread of, and subsequently eradicate, sheep scrapie in Iceland. Affected flocks were culled, premises were disinfected and, after 2–3 years, restocked with lambs from scrapie-free areas. Between 1978 and 2004, scrapie recurred on 33 farms. Nine of these recurrences occurred 14–21 years after culling, apparently as the result of environmental contamination, but outside entry could not always be absolutely excluded. Of special interest was one farm with a small, completely self-contained flock where scrapie recurred 18 years after culling, 2 years after some lambs had been housed in an old sheephouse that had never been disinfected. Epidemiological investigation established with near certitude that the disease had not been introduced from the outside and it is concluded that the agent may have persisted in the old sheep-house for at least 16 years.

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

Gudmundur Georgsson1, Sigurdur Sigurdarson2 and Paul Brown3 



Using in vitro Prion replication for high sensitive detection of prions and prionlike proteins and for understanding mechanisms of transmission. 

Claudio Soto Mitchell Center for Alzheimer's diseases and related Brain disorders, Department of Neurology, University of Texas Medical School at Houston. 

Prion and prion-like proteins are misfolded protein aggregates with the ability to selfpropagate to spread disease between cells, organs and in some cases across individuals. I n T r a n s m i s s i b l e s p o n g i f o r m encephalopathies (TSEs), prions are mostly composed by a misfolded form of the prion protein (PrPSc), which propagates by transmitting its misfolding to the normal prion protein (PrPC). The availability of a procedure to replicate prions in the laboratory may be important to study the mechanism of prion and prion-like spreading and to develop high sensitive detection of small quantities of misfolded proteins in biological fluids, tissues and environmental samples. Protein Misfolding Cyclic Amplification (PMCA) is a simple, fast and efficient methodology to mimic prion replication in the test tube. PMCA is a platform technology that may enable amplification of any prion-like misfolded protein aggregating through a seeding/nucleation process. In TSEs, PMCA is able to detect the equivalent of one single molecule of infectious PrPSc and propagate prions that maintain high infectivity, strain properties and species specificity. Using PMCA we have been able to detect PrPSc in blood and urine of experimentally infected animals and humans affected by vCJD with high sensitivity and specificity. Recently, we have expanded the principles of PMCA to amplify amyloid-beta (Aβ) and alphasynuclein (α-syn) aggregates implicated in Alzheimer's and Parkinson's diseases, respectively. Experiments are ongoing to study the utility of this technology to detect Aβ and α-syn aggregates in samples of CSF and blood from patients affected by these diseases.

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

***>>> Recently, we have been using PMCA to study the role of environmental prion contamination on the horizontal spreading of TSEs. These experiments have focused on the study of the interaction of prions with plants and environmentally relevant surfaces. Our results show that plants (both leaves and roots) bind tightly to prions present in brain extracts and excreta (urine and feces) and retain even small quantities of PrPSc for long periods of time. Strikingly, ingestion of prioncontaminated leaves and roots produced disease with a 100% attack rate and an incubation period not substantially longer than feeding animals directly with scrapie brain homogenate. Furthermore, plants can uptake prions from contaminated soil and transport them to different parts of the plant tissue (stem and leaves). Similarly, prions bind tightly to a variety of environmentally relevant surfaces, including stones, wood, metals, plastic, glass, cement, etc. Prion contaminated surfaces efficiently transmit prion disease when these materials were directly injected into the brain of animals and strikingly when the contaminated surfaces were just placed in the animal cage. These findings demonstrate that environmental materials can efficiently bind infectious prions and act as carriers of infectivity, suggesting that they may play an important role in the horizontal transmission of the disease.

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

Since its invention 13 years ago, PMCA has helped to answer fundamental questions of prion propagation and has broad applications in research areas including the food industry, blood bank safety and human and veterinary disease diagnosis. 


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


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


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


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


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


PPo4-4: 

Survival and Limited Spread of TSE Infectivity after Burial 



Discussion Classical scrapie is an environmentally transmissible disease because it has been reported in naïve, supposedly previously unexposed sheep placed in pastures formerly occupied by scrapie-infected sheep (4, 19, 20). 

Although the vector for disease transmission is not known, soil is likely to be an important reservoir for prions (2) where – based on studies in rodents – prions can adhere to minerals as a biologically active form (21) and remain infectious for more than 2 years (22). 

Similarly, chronic wasting disease (CWD) has re-occurred in mule deer housed in paddocks used by infected deer 2 years earlier, which was assumed to be through foraging and soil consumption (23). 

Our study suggested that the risk of acquiring scrapie infection was greater through exposure to contaminated wooden, plastic, and metal surfaces via water or food troughs, fencing, and hurdles than through grazing. 

Drinking from a water trough used by the scrapie flock was sufficient to cause infection in sheep in a clean building. 

Exposure to fences and other objects used for rubbing also led to infection, which supported the hypothesis that skin may be a vector for disease transmission (9). 

The risk of these objects to cause infection was further demonstrated when 87% of 23 sheep presented with PrPSc in lymphoid tissue after grazing on one of the paddocks, which contained metal hurdles, a metal lamb creep and a water trough in contact with the scrapie flock up to 8 weeks earlier, whereas no infection had been demonstrated previously in sheep grazing on this paddock, when equipped with new fencing and field furniture. 

When the contaminated furniture and fencing were removed, the infection rate dropped significantly to 8% of 12 sheep, with soil of the paddock as the most likely source of infection caused by shedding of prions from the scrapie-infected sheep in this paddock up to a week earlier. 

This study also indicated that the level of contamination of field furniture sufficient to cause infection was dependent on two factors: stage of incubation period and time of last use by scrapie-infected sheep. 

Drinking from a water trough that had been used by scrapie sheep in the predominantly pre-clinical phase did not appear to cause infection, whereas infection was shown in sheep drinking from the water trough used by scrapie sheep in the later stage of the disease. 

It is possible that contamination occurred through shedding of prions in saliva, which may have contaminated the surface of the water trough and subsequently the water when it was refilled. 

Contamination appeared to be sufficient to cause infection only if the trough was in contact with sheep that included clinical cases. 

Indeed, there is an increased risk of bodily fluid infectivity with disease progression in scrapie (24) and CWD (25) based on PrPSc detection by sPMCA. 

Although ultraviolet light and heat under natural conditions do not inactivate prions (26), furniture in contact with the scrapie flock, which was assumed to be sufficiently contaminated to cause infection, did not act as vector for disease if not used for 18 months, which suggest that the weathering process alone was sufficient to inactivate prions. 

PrPSc detection by sPMCA is increasingly used as a surrogate for infectivity measurements by bioassay in sheep or mice. 

In this reported study, however, the levels of PrPSc present in the environment were below the limit of detection of the sPMCA method, yet were still sufficient to cause infection of in-contact animals. 

In the present study, the outdoor objects were removed from the infected flock 8 weeks prior to sampling and were positive by sPMCA at very low levels (2 out of 37 reactions). 

As this sPMCA assay also yielded 2 positive reactions out of 139 in samples from the scrapie-free farm, the sPMCA assay could not detect PrPSc on any of the objects above the background of the assay. 

False positive reactions with sPMCA at a low frequency associated with de novo formation of infectious prions have been reported (27, 28). 

This is in contrast to our previous study where we demonstrated that outdoor objects that had been in contact with the scrapie-infected flock up to 20 days prior to sampling harbored PrPSc that was detectable by sPMCA analysis [4 out of 15 reactions (12)] and was significantly more positive by the assay compared to analogous samples from the scrapie-free farm. 

This discrepancy could be due to the use of a different sPMCA substrate between the studies that may alter the efficiency of amplification of the environmental PrPSc. 

In addition, the present study had a longer timeframe between the objects being in contact with the infected flock and sampling, which may affect the levels of extractable PrPSc. 

Alternatively, there may be potentially patchy contamination of this furniture with PrPSc, which may have been missed by swabbing. 

The failure of sPMCA to detect CWD-associated PrP in saliva from clinically affected deer despite confirmation of infectivity in saliva-inoculated transgenic mice was associated with as yet unidentified inhibitors in saliva (29), and it is possible that the sensitivity of sPMCA is affected by other substances in the tested material. 

In addition, sampling of amplifiable PrPSc and subsequent detection by sPMCA may be more difficult from furniture exposed to weather, which is supported by the observation that PrPSc was detected by sPMCA more frequently in indoor than outdoor furniture (12). 

A recent experimental study has demonstrated that repeated cycles of drying and wetting of prion-contaminated soil, equivalent to what is expected under natural weathering conditions, could reduce PMCA amplification efficiency and extend the incubation period in hamsters inoculated with soil samples (30). 

This seems to apply also to this study even though the reduction in infectivity was more dramatic in the sPMCA assays than in the sheep model. 

Sheep were not kept until clinical end-point, which would have enabled us to compare incubation periods, but the lack of infection in sheep exposed to furniture that had not been in contact with scrapie sheep for a longer time period supports the hypothesis that prion degradation and subsequent loss of infectivity occurs even under natural conditions. 

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

These results suggest that the VRQ/VRQ sheep model may be more sensitive than sPMCA for the detection of environmentally associated scrapie, and suggest that extremely low levels of scrapie contamination are able to cause infection in susceptible sheep genotypes. 

Keywords: classical scrapie, prion, transmissible spongiform encephalopathy, sheep, field furniture, reservoir, serial protein misfolding cyclic amplification 


 Wednesday, December 16, 2015 

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


THURSDAY, OCTOBER 04, 2018 

Cervid to human prion transmission 5R01NS088604-04 Update



SATURDAY, NOVEMBER 10, 2018 

cwd, bse, scrapie, cjd, tse prion updated November 10 2018



THURSDAY, OCTOBER 25, 2018 

***> Norway New additional requirements for imports of hay and straw for animal feed from countries outside the EEA due to CWD TSE Prion




Terry S. Singeltary Sr.

posted by Terry S. Singeltary Sr. at 9:16 AM

0 Comments:

Post a Comment

Subscribe to Post Comments [Atom]

<< Home