Tuesday, December 05, 2017

Norway 30,000 deer animals have so far been tested for Skrantesyke chronic wasting disease CWD TSE PRION DISEASE

30,000 deer animals have so far been tested for scratch sickness

Published 04.12.2017 

The veterinary institute has so far tested 30,000 deer for chronic wasting disease (CWD), which is the largest sampling program since kugalskap was at its most intense about 15 years ago. "The results show that the prevalence in Nordfjella is low, which gives hope to preserve fresh wildlife in Norway," says CWD coordinator Jørn Våge at the Veterinary Institute. 

Each morning, sample material was submitted to the Veterinary Institute for analysis. Samples from 10,000 animals were analyzed in 2016 and so far in 2017, 20,000 animals have been tested. The record for one day has so far been 963 samples. Photo: Bryndis Holm, Veterinary Institute.2 Chronic Wasting Disease (CWD) is a prion disease such as scratch sickness in sheep or cowworms, where flawed protein picks up in the brain and causes great suffering and death to the affected individuals. When CWD was discovered by the Norwegian Veterinary Institute last year, it was the first case in Europe, and extensive sampling of Norwegian deer animals (elk, wild boar, tamrein, deer and deer) was initiated.

"It is important to have good professional preparedness to handle animal diseases. The veterinary institute has shown that they have high professional competence in the work of CWD / skrant disease. I am also impressed by the pace the institute has managed to stop in examining the great number of tests. Quick test answers are important for testing against CWD not to create too big practical challenges for hunters, slaughterhouses and cuts, victory of agriculture and food minister Jon Georg Dale.

If no contaminants are found, all hunters submitting samples will receive a response within 24 hours, from the exam, the Veterinary Institute will arrive.

Learning after 30,000 samples

Researchers at the Veterinary Institute believe that important lessons can be extracted from the 30,000 samples analyzed since the discovery of the disease last year.

The spread of CWD among wild fauna in Nordfjella is about one percent, as the researchers estimated it would be. This was the basis for advising on the remediation of wild bushes in the area. To date, 8 wildcats with CWD have been found among the 775 tested in Nordfjella. These cases have not been distinguished from the classical infectious type that has spread over the last decade in the United States and Canada, with major negative consequences for the animal tribes.

Important lessons are also that CWD cases on elk and deer differ from that in Nordfjella and North America. These cases appear to be more similar to other atypical prion diseases affecting elderly individuals and which can occur spontaneously without infection. It has been tested over 15,000 moons and deer. So far, atypical CWD has been detected in three moons and one deer. 

"As far as the prevalence is concerned, it seems to be as planned in Nordfjella, and the findings outside the area seem to be another type of CWD, which means that we still have the hope to prevent the disease seen at wild boar to gain a foothold in Norway. It assumes we will remove the infection. To give up this attempt will in a wide perspective be to give up the idea of ​​future fresh deer wildlife stocks, "said Våge.

He emphasizes that the longer time you spend on removing the infected wildlife strain in Nordfjella, the greater the chance of spreading out of the area, and that the situation becomes even more difficult to handle.

Greatest in many years

Each morning, sample material was submitted to the Veterinary Institute for analysis. Samples from 10,000 animals were analyzed in 2016 and so far in 2017, 20,000 animals have been tested. The record for one day has so far been 963 samples. This is the most comprehensive sampling program since kugalskap was at its most intense in the early 2000s. At the start of the project, an upgrading of the machinery was made and crew was strengthened. 

"It has undoubtedly been a tiring harvest with many long days for more employees. But we have an understanding of the seriousness of the situation and that work has to be done, says laboratory pathologist at the Veterinary Institute, Randi Terland




please understand that this was translation from internet...terry


WEDNESDAY, NOVEMBER 29, 2017

 Norway another case of Skrantesjuke CWD TSE Prion Adult Reindeer pitcher field in Nordfjella (preliminary testing) 13th case if confirmed



>>>These cases appear to be more similar to other atypical prion diseases affecting elderly individuals and which can occur spontaneously without infection. <<<


Le Høyt! Laugh Out Loud ! LOL!


Oh, what a tangled web we weave when first we practice to deceive! 


***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.***


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.
 
==============
 

 
 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.
 


First case of chronic wasting disease in Europe in a Norwegian free-ranging reindeer 

Sylvie L. Benestad1*, Gordon Mitchell2 , Marion Simmons3 , Bjørnar Ytrehus4 and Turid Vikøren1 

In contrast to classical scrapie is Nor98/atypical scrapie diagnosed in sheep in Norway. Between five and 13 cases have been identified each year the past 10 years, and they are found over the whole country, including where the CWD reindeer was discovered. Whether Nor98/atypical scrapie could be the source of CWD in Norway cannot be excluded, despite the fact that, as it could be expected in case of direct transmission, the distinctive molecular signature of Nor98/atypical scrapie, a multiband WB pattern [18] was not observed in the present reindeer... 

Greetings TSE prion world, 

i am seeing more and more references to the atypical Nor-98-type CWD TSE Prion in Norway as being of the non-infectious or non-infective variant. with science documented to date, i do not believe that any CWD Skrantesjuke TSE Prion typical or atypical in Norway or anywhere else can be classified as ''non-infective variant''. IF, Norway takes the USDA OIE views and makes atypical Nor-98 type CWD in Deer a International trading commodity fueled by junk science, as they did with sheep, i.e. no trade restrictions for Nor-98 in sheep, the world should then weep...terry


Nor-98 atypical Scrapie Transmission Studies Review

 
MONDAY, APRIL 25, 2011 

Experimental Oral Transmission of Atypical Scrapie to Sheep

Volume 17, Number 5–May 2011 

Research 

Experimental Oral Transmission of Atypical Scrapie to Sheep 

Marion M. Simmons, S. Jo Moore,1 Timm Konold, Lisa Thurston, Linda A. Terry, Leigh Thorne, Richard Lockey, Chris Vickery, Stephen A.C. Hawkins, Melanie J. Chaplin, and John Spiropoulos –Weybridge, Addlestone, UK

Suggested citation for this article

Abstract 

To investigate the possibility of oral transmission of atypical scrapie in sheep and determine the distribution of infectivity in the animals' peripheral tissues, we challenged neonatal lambs orally with atypical scrapie; they were then killed at 12 or 24 months. Screening test results were negative for disease-specific prion protein in all but 2 recipients; they had positive results for examination of brain, but negative for peripheral tissues. Infectivity of brain, distal ileum, and spleen from all animals was assessed in mouse bioassays; positive results were obtained from tissues that had negative results on screening. These findings demonstrate that atypical scrapie can be transmitted orally and indicate that it has the potential for natural transmission and iatrogenic spread through animal feed. Detection of infectivity in tissues negative by current surveillance methods indicates that diagnostic sensitivity is suboptimal for atypical scrapie, and potentially infectious material may be able to pass into the human food chain. 

 SNIP... 

Discussion This study is still ongoing and will not be completed until 2012. However, the current interim report documents the successful oral transmission of atypical scrapie, confirms that the disease phenotype is retained following transmission by this route in AHQ/AHQ sheep, and indicates that infectivity can be demonstrated in the gut in the absence of detectable PrPSc at least as early as 12 months after exposure.

One sheep (animal 12) culled at 24 months post inoculation displayed abnormalities in behavior and movement suggestive of atypical scrapie. Signs like ataxia with head tremor and circling have been described in experimental (19) and natural (3,30) disease, which was attributed to lesions in the cerebellum and forebrain, respectively, corresponding with PrPSc accumulation in these areas (20,24).

By contrast, animal 11, which had confirmed atypical scrapie based on postmortem tests, was considered clinically normal. The less severe and limited PrPSc accumulation in the brain of this sheep than in animal 12 may explain the absence of clinical abnormalities, which is supported by our findings in goats with scrapie in which more extensive PrPSc accumulation in the brain was usually associated with a more severe clinical disease (25).

Although all TSEs are transmissible after intracerebral challenge to a susceptible host, only some are infectious under natural conditions. Therefore, it was important from a pathogenesis and disease control perspective to establish whether or not oral transmission can be successful. However, the challenge model in this study exposed animals as neonates, when the esophageal groove is operational and the lambs are physiologically monogastric. Exposure of 3-month-old ruminating animals to similar amounts of positive brain by the oral route have so far not resulted in any clinical disease, with all animals still alive >1,500 days post challenge (M.M. Simmons, unpub. data), but most natural cases have been recorded in animals older than this, so these animals may still progress to disease in the next few years. Since this challenge study in older animals has no time-kill component, and no losses caused by unrelated disease have occurred, whether any of these sheep are in a preclinical phase of disease is unknown. Unfortunately, the absence of detectable PrPSc in lymphoreticular tissues of sheep with atypical scrapie precludes the use of biopsies to ascertain early infection in these animals.

Transmission may be more efficient in newborn animals; the incubation periods of sheep orally infected with classical scrapie were significantly shorter in sheep challenged at 14 days of age than those challenged at 6 months of age (31). If, however, oral transmission is only effective in such young animals, then field exposure would most likely have to be through milk, which is known to be a highly effective route of transmission for classical scrapie (32). No data are currently available on the potential infectivity of milk from animals with atypical scrapie.

Successful oral transmission also raises questions regarding the pathogenesis of this form of disease. There must be passage of the infectious agent from the alimentary canal to the brain through one of several possible routes, most likely those that have been suggested and discussed in detail for other TSEs, for example, retrograde neuronal transportation either directly (33–35) or through lymphoid structures or hematogenously (36). Infectivity in the absence of readily demonstrable PrPSc has been reported (37–39), and although the mouse bioassay may detect evidence of disease in other tissues, these data may not be available for at least another 2 years. More protease-sensitive forms of PrPSc may be broken down more efficiently within cells and thus do not accumulate in peripheral tissues (19), enabling atypical PrPSc to transit the digestive tract and disseminate through other systems in small amounts before accumulating detectably in the central nervous system.

Although we do not have epidemiologic evidence that supports the efficient spread of disease in the field, these data imply that disease is potentially transmissible under field situations and that spread through animal feed may be possible if the current feed restrictions were to be relaxed. Additionally, almost no data are available on the potential for atypical scrapie to transmit to other food animal species, certainly by the oral route. However, work with transgenic mice has demonstrated the potential susceptibility of pigs, with the disturbing finding that the biochemical properties of the resulting PrPSc have changed on transmission (40). The implications of this observation for subsequent transmission and host target range are currently unknown.

How reassuring is this absence of detectable PrPSc from a public health perspective? The bioassays performed in this study are not titrations, so the infectious load of the positive gut tissues cannot be quantified, although infectivity has been shown unequivocally. No experimental data are currently available on the zoonotic potential of atypical scrapie, either through experimental challenge of humanized mice or any meaningful epidemiologic correlation with human forms of TSE. However, the detection of infectivity in the distal ileum of animals as young as 12 months, in which all the tissues tested were negative for PrPSc by the currently available screening and confirmatory diagnostic tests, indicates that the diagnostic sensitivity of current surveillance methods is suboptimal for detecting atypical scrapie and that potentially infectious material may be able to pass into the human food chain undetected. 


Increased Atypical Scrapie Detections

Press reports indicate that increased surveillance is catching what otherwise would have been unreported findings of atypical scrapie in sheep. In 2009, five new cases have been reported in Quebec, Ontario, Alberta, and Saskatchewan. With the exception of Quebec, all cases have been diagnosed as being the atypical form found in older animals. Canada encourages producers to join its voluntary surveillance program in order to gain scrapie-free status. The World Animal Health will not classify Canada as scrapie-free until no new cases are reported for seven years. The Canadian Sheep Federation is calling on the government to fund a wider surveillance program in order to establish the level of prevalence prior to setting an eradication date. Besides long-term testing, industry is calling for a compensation program for farmers who report unusual deaths in their flocks.


Atypical scrapie in Australia

RW Cook,a* J Bingham,bAS Besier,cCL Bayley,dM Hawes,ePL Shearer,fM Yamada,bJ Bergfeld,bDT Williamsband DJ Middletonb Background Since its initial detection in Norway in 1998, atypical scrapie (‘atypical/Nor98 scrapie’) has been reported in sheep in the majority of European countries (including in regions free of classical scrapie) and in the Falkland Islands, the USA, Canada,New Zealand and Australia.

Case series The diagnosis in Australia of atypical scrapie in four Merino and one Merino-cross sheep showing clinical signs of neurological disease was based on the detection of grey matter neuropil vacuolation (spongiform change) in the brain (particularly inthe molecular layer of the cerebellar cortex) and associated abnormal prion protein (PrPSc) deposition in both grey and white matter. Changes were minimal in the caudal brainstem, the predilection site for lesions of classical scrapie.Conclusion The distinctive lesion profile of atypical scrapie in these five sheep highlights the diagnostic importance of routine histological evaluation of the cerebellum for evidence of neuropil vacuolation and associated PrPSc deposition in adult sheep with suspected neurological disease.

Keywords atypical scrapie; prion disease; sheep; transmissible spongiform encephalopathy 

Abbreviations ANZSDP, Australian and New Zealand StandardDiagnostic Procedure; CNS, central nervous system; DMNV, dorsalmotor nucleus of the vagus nerve; H&E, haematoxylin and eosin;IHC, immunohistochemistry; NTSESP, National TSE SurveillanceProgram; PrPSc, abnormal prion protein isomer; TSE, transmissiblespongiform encephalopathy. Aust Vet J 2016;94:452–455 doi: 10.1111/avj.12529


Friday, February 11, 2011

Atypical/Nor98 Scrapie Infectivity in Sheep Peripheral Tissues

snip...

The presence of infectivity in peripheral tissues that enter the food chain clearly indicates that the risk of dietary exposure to Atypical/Nor98 scrapie cannot be disregarded. However, according to our observations, in comparison to the brain, the infectious titres in the peripheral tissues were five log10 lower in Atypical/Nor98 scrapie than in classical scrapie. Therefore, the reduction of the relative exposure risk following SRM removal (CNS, head, spleen and ileum) is probably significantly higher in Atypical/Nor98 scrapie cases than in classical scrapie cases. However, considering the currently estimated prevalence of Atypical/Nor98 scrapie in healthy slaughtered EU population [10], it is probable that atypical scrapie infectivity enters in the food chain despite the prevention measures in force.

Finally, the capacity of Atypical/Nor98 scrapie agent (and more generally of small ruminants TSE agents) to cross species barrier that naturally limits the transmission risk is insufficiently documented. Recently, the transmission of an Atypical/Nor98 scrapie isolate was reported into transgenic mice over-expressing the porcine PrP [47]. Such results cannot directly be extrapolated to natural exposure conditions and natural hosts. However, they underline the urgent need for further investigations on the potential capacity of Atypical/Nor98 scrapie to propagate in other species than small ruminants.

snip...please see full text thanks to the Authors and plospathogens.org/


PR-26

NOR98 SHOWS MOLECULAR FEATURES REMINISCENT OF GSS

R. Nonno1, E. Esposito1, G. Vaccari1, E. Bandino2, M. Conte1, B. Chiappini1, S. Marcon1, M. Di Bari1, S.L. Benestad3, U. Agrimi1 1 Istituto Superiore di Sanità, Department of Food Safety and Veterinary Public Health, Rome, Italy (romolo.nonno@iss.it); 2 Istituto Zooprofilattico della Sardegna, Sassari, Italy; 3 National Veterinary Institute, Department of Pathology, Oslo, Norway

Molecular variants of PrPSc are being increasingly investigated in sheep scrapie and are generally referred to as “atypical” scrapie, as opposed to “classical scrapie”. Among the atypical group, Nor98 seems to be the best identified. We studied the molecular properties of Italian and Norwegian Nor98 samples by WB analysis of brain homogenates, either untreated, digested with different concentrations of proteinase K, or subjected to enzymatic deglycosylation. The identity of PrP fragments was inferred by means of antibodies spanning the full PrP sequence. We found that undigested brain homogenates contain a Nor98-specific PrP fragment migrating at 11 kDa (PrP11), truncated at both the C-terminus and the N-terminus, and not N-glycosylated. After mild PK digestion, Nor98 displayed full-length PrP (FL-PrP) and N-glycosylated C-terminal fragments (CTF), along with increased levels of PrP11. Proteinase K digestion curves (0,006-6,4 mg/ml) showed that FL-PrP and CTF are mainly digested above 0,01 mg/ml, while PrP11 is not entirely digested even at the highest concentrations, similarly to PrP27-30 associated with classical scrapie. Above 0,2 mg/ml PK, most Nor98 samples showed only PrP11 and a fragment of 17 kDa with the same properties of PrP11, that was tentatively identified as a dimer of PrP11. Detergent solubility studies showed that PrP11 is insoluble in 2% sodium laurylsorcosine and is mainly produced from detergentsoluble, full-length PrPSc. Furthermore, among Italian scrapie isolates, we found that a sample with molecular and pathological properties consistent with Nor98 showed plaque-like deposits of PrPSc in the thalamus when the brain was analysed by PrPSc immunohistochemistry. Taken together, our results show that the distinctive pathological feature of Nor98 is a PrP fragment spanning amino acids ~ 90-155. This fragment is produced by successive N-terminal and C-terminal cleavages from a full-length and largely detergent-soluble PrPSc, is produced in vivo and is extremely resistant to PK digestion. Intriguingly, these conclusions suggest that some pathological features of Nor98 are reminiscent of Gerstmann-Sträussler-Scheinker disease.

119


P03.141

Aspects of the Cerebellar Neuropathology in Nor98

Gavier-Widén, D1; Benestad, SL2; Ottander, L1; Westergren, E1 1National Veterinary Insitute, Sweden; 2National Veterinary Institute,

Norway Nor98 is a prion disease of old sheep and goats. This atypical form of scrapie was first described in Norway in 1998. Several features of Nor98 were shown to be different from classical scrapie including the distribution of disease associated prion protein (PrPd) accumulation in the brain. The cerebellum is generally the most affected brain area in Nor98. The study here presented aimed at adding information on the neuropathology in the cerebellum of Nor98 naturally affected sheep of various genotypes in Sweden and Norway. A panel of histochemical and immunohistochemical (IHC) stainings such as IHC for PrPd, synaptophysin, glial fibrillary acidic protein, amyloid, and cell markers for phagocytic cells were conducted. The type of histological lesions and tissue reactions were evaluated. The types of PrPd deposition were characterized. The cerebellar cortex was regularly affected, even though there was a variation in the severity of the lesions from case to case. Neuropil vacuolation was more marked in the molecular layer, but affected also the granular cell layer. There was a loss of granule cells. Punctate deposition of PrPd was characteristic. It was morphologically and in distribution identical with that of synaptophysin, suggesting that PrPd accumulates in the synaptic structures. PrPd was also observed in the granule cell layer and in the white matter. The pathology features of Nor98 in the cerebellum of the affected sheep showed similarities with those of sporadic Creutzfeldt-Jakob disease in humans.


A newly identified type of scrapie agent can naturally infect sheep with resistant PrP genotypes

Annick Le Dur*,?, Vincent Béringue*,?, Olivier Andréoletti?, Fabienne Reine*, Thanh Lan Laï*, Thierry Baron§, Bjørn Bratberg¶, Jean-Luc Vilotte?, Pierre Sarradin**, Sylvie L. Benestad¶, and Hubert Laude*,?? +Author Affiliations

*Virologie Immunologie Moléculaires and ?Génétique Biochimique et Cytogénétique, Institut National de la Recherche Agronomique, 78350 Jouy-en-Josas, France; ?Unité Mixte de Recherche, Institut National de la Recherche Agronomique-Ecole Nationale Vétérinaire de Toulouse, Interactions Hôte Agent Pathogène, 31066 Toulouse, France; §Agence Française de Sécurité Sanitaire des Aliments, Unité Agents Transmissibles Non Conventionnels, 69364 Lyon, France; **Pathologie Infectieuse et Immunologie, Institut National de la Recherche Agronomique, 37380 Nouzilly, France; and ¶Department of Pathology, National Veterinary Institute, 0033 Oslo, Norway

Edited by Stanley B. Prusiner, University of California, San Francisco, CA (received for review March 21, 2005)

Abstract Scrapie in small ruminants belongs to transmissible spongiform encephalopathies (TSEs), or prion diseases, a family of fatal neurodegenerative disorders that affect humans and animals and can transmit within and between species by ingestion or inoculation. Conversion of the host-encoded prion protein (PrP), normal cellular PrP (PrPc), into a misfolded form, abnormal PrP (PrPSc), plays a key role in TSE transmission and pathogenesis. The intensified surveillance of scrapie in the European Union, together with the improvement of PrPSc detection techniques, has led to the discovery of a growing number of so-called atypical scrapie cases. These include clinical Nor98 cases first identified in Norwegian sheep on the basis of unusual pathological and PrPSc molecular features and "cases" that produced discordant responses in the rapid tests currently applied to the large-scale random screening of slaughtered or fallen animals. Worryingly, a substantial proportion of such cases involved sheep with PrP genotypes known until now to confer natural resistance to conventional scrapie. Here we report that both Nor98 and discordant cases, including three sheep homozygous for the resistant PrPARR allele (A136R154R171), efficiently transmitted the disease to transgenic mice expressing ovine PrP, and that they shared unique biological and biochemical features upon propagation in mice. These observations support the view that a truly infectious TSE agent, unrecognized until recently, infects sheep and goat flocks and may have important implications in terms of scrapie control and public health.


Monday, December 1, 2008

When Atypical Scrapie cross species barriers

Authors

Andreoletti O., Herva M. H., Cassard H., Espinosa J. C., Lacroux C., Simon S., Padilla D., Benestad S. L., Lantier F., Schelcher F., Grassi J., Torres, J. M., UMR INRA ENVT 1225, Ecole Nationale Veterinaire de Toulouse.France; ICISA-INlA, Madrid, Spain; CEA, IBiTec-5, DSV, CEA/Saclay, Gif sur Yvette cedex, France; National Veterinary Institute, Postboks 750 Sentrum, 0106 Oslo, Norway, INRA IASP, Centre INRA de Tours, 3738O Nouzilly, France.

Content

Atypical scrapie is a TSE occurring in small ruminants and harbouring peculiar clinical, epidemiological and biochemical properties. Currently this form of disease is identified in a large number of countries. In this study we report the transmission of an atypical scrapie isolate through different species barriers as modeled by transgenic mice (Tg) expressing different species PRP sequence.

The donor isolate was collected in 1995 in a French commercial sheep flock. inoculation into AHQ/AHQ sheep induced a disease which had all neuro-pathological and biochemical characteristics of atypical scrapie. Transmitted into Transgenic mice expressing either ovine or PrPc, the isolate retained all the described characteristics of atypical scrapie.

Surprisingly the TSE agent characteristics were dramatically different v/hen passaged into Tg bovine mice. The recovered TSE agent had biological and biochemical characteristics similar to those of atypical BSE L in the same mouse model. Moreover, whereas no other TSE agent than BSE were shown to transmit into Tg porcine mice, atypical scrapie was able to develop into this model, albeit with low attack rate on first passage.

Furthermore, after adaptation in the porcine mouse model this prion showed similar biological and biochemical characteristics than BSE adapted to this porcine mouse model. Altogether these data indicate.

(i) the unsuspected potential abilities of atypical scrapie to cross species barriers

(ii) the possible capacity of this agent to acquire new characteristics when crossing species barrier

These findings raise some interrogation on the concept of TSE strain and on the origin of the diversity of the TSE agents and could have consequences on field TSE control measures.


APHIS USDA atypical Nor-98 Scrapie

Nor98‐like (nonclassical) scrapie and classical scrapie are separate diseases with distinct features.

Transmission 

Classical scrapie is an infectious disease that is transmitted to other sheep and goats under natural conditions.

Nor98‐like scrapie is either not transmitted or is poorly transmitted, under natural conditions. Many scientists believe that Nor98‐like scrapie is not an infectious disease under natural conditions and that it is instead caused by a random conversion of the normal prion protein into the abnormal form (often referred to as “sporadic”). 


MONDAY, NOVEMBER 30, 2009 

*** USDA AND OIE COLLABORATE TO EXCLUDE ATYPICAL SCRAPIE NOR-98 ANIMAL HEALTH CODE ***



atypical TSE is a political disease $$$


atypical Bovine Spongiform Encephalopathy and SPORADIC CJD, and the SPONTANEOUS MYTH surrounding that, like Norway is trying to do with Chronic Wasting Disease CWD TSE Prion aka MAD DEER DISEASE.

THE INFAMOUS old COW AND PEOPLE, old cow disease, that officials and media claim falsely that is not transmissible, or is a spontaneous happening from nothing like sporadic CJD, like Norway is trying to do with Chronic Wasting Disease CWD TSE Prion. junk science at it's finest.

let's analyze the science to date including transmission studies with atypical Transmissible Spongiform Encephalopathy BSE, Scrapie, CWD, disease, to date, shall we...terry


THURSDAY, JULY 20, 2017 

USDA OIE Alabama Atypical L-type BASE Bovine Spongiform Encephalopathy BSE animal feeds for ruminants rule, 21 CFR 589.200



SUNDAY, JULY 23, 2017

atypical L-type BASE Bovine Amyloidotic Spongiform Encephalopathy BSE TSE PRION



SUNDAY, JULY 23, 2017

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



THURSDAY, AUGUST 17, 2017 

JAVMA NEWS Atypical BSE found in Alabama cow September 01, 2017



2012 ATYPICAL L-TYPE BASE BSE TSE PRION CALIFORNIA ‘confirmed’ 

Saturday, August 4, 2012

*** Final Feed Investigation Summary - California BSE Case - July 2012



SPONTANEOUS ATYPICAL BOVINE SPONGIFORM ENCEPHALOPATHY

***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.***



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. ***

P.9.21

Molecular characterization of BSE in Canada

Jianmin Yang 1 , Sandor Dudas 2 , Catherine Graham 2 , Markus Czub 3 , Tim McAllister 1 , Stefanie Czub 1 1 Agriculture and Agri-Food Canada Research Centre, Canada; 2 National and OIE BSE Reference Laboratory, Canada; 3 University of Calgary, Canada

Background: Three BSE types (classical and two atypical) have been identified on the basis of molecular characteristics of the misfolded protein associated with the disease. To date, each of these three types have been detected in Canadian cattle. Objectives: This study was conducted to further characterize the 16 Canadian BSE cases based on the biochemical properties of there associated PrPres.

Methods: Immuno-reactivity, molecular weight, glycoform profiles and relative proteinase K sensitivity of the PrPres from each of the 16 confirmed Canadian BSE cases was determined using modified Western blot analysis.

Results: Fourteen of the 16 Canadian BSE cases were C type, 1 was H type and 1 was L type. The Canadian H and L-type BSE cases exhibited size shifts and changes in glycosylation similar to other atypical BSE cases. PK digestion under mild and stringent conditions revealed a reduced protease resistance of the atypical cases compared to the C-type cases. N terminal-specific antibodies bound to PrPres from H type but not from C or L type. The C-terminal-specific antibodies resulted in a shift in the glycoform profile and detected a fourth band in the Canadian H-type BSE.

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;



Thursday, November 16, 2017 

Texas Natural Meats Recalls Beef Products Due To Possible Specified Risk Materials Contamination



***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



CH1641 atypical scrapie or atypical BSE or both ???


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.

WS-02

Scrapie in swine: A diagnostic challenge

Justin J Greenlee1, Robert A Kunkle1, Jodi D Smith1, Heather W. Greenlee2

1National Animal Disease Center, US Dept. of Agriculture, Agricultural Research Service, United States; 2Iowa State University College of Veterinary Medicine

A naturally occurring prion disease has not been recognized in swine, but the agent of bovine spongiform encephalopathy does transmit to swine by experimental routes. Swine are thought to have a robust species barrier when exposed to the naturally occurring prion diseases of other species, but the susceptibility of swine to the agent of sheep scrapie has not been thoroughly tested.

Since swine can be fed rations containing ruminant derived components in the United States and many other countries, we conducted this experiment to test the susceptibility of swine to U.S. scrapie isolates by intracranial and oral inoculation. Scrapie inoculum was a pooled 10% (w/v) homogenate derived from the brains of clinically ill sheep from the 4th passage of a serial passage study of the U.S scrapie agent (No. 13-7) through susceptible sheep that were homozygous ARQ at prion protein residues 136, 154, and 171, respectively. Pigs were inoculated intracranially (n=19) with a single 0.75 ml dose or orally (n=24) with 15 ml repeated on 4 consecutive days. Necropsies were done on a subset of animals at approximately six months post inoculation (PI), at the time the pigs were expected to reach market weight. Remaining pigs were maintained and monitored for clinical signs of TSE until study termination at 80 months PI or when removed due to intercurrent disease (primarily lameness). Brain samples were examined by immunohistochemistry (IHC), western blot (WB), and enzyme-linked immunosorbent assay (ELISA). Brain tissue from a subset of pigs in each inoculation group was used for bioassay in mice expressing porcine PRNP.

At six-months PI, no evidence of scrapie infection was noted by any diagnostic method. However, at 51 months of incubation or greater, 5 animals were positive by one or more methods: IHC (n=4), WB (n=3), or ELISA (n=5). Interestingly, positive bioassay results were obtained from all inoculated groups (oral and intracranial; market weight and end of study).

Swine inoculated with the agent of scrapie by the intracranial and oral routes do not accumulate abnormal prion protein (PrPSc) to a level detectable by IHC or WB by the time they reach typical market age and weight. However, strong support for the fact that swine are potential hosts for the agent of scrapie comes from positive bioassay from both intracranially and orally inoculated pigs and multiple diagnostic methods demonstrating abnormal prion protein in intracranially inoculated pigs with long incubation times.

Curriculum Vitae

Dr. Greenlee is Research Veterinary Medical Officer in the Virus and Prion Research Unit at the National Animal Disease Center, US Department of Agriculture, Agricultural Research Service. He applies his specialty in veterinary anatomic pathology to focused research on the intra- and interspecies transmission of prion diseases in livestock and the development of antemortem diagnostic assays for prion diseases. In addition, knockout and transgenic mouse models are used to complement ongoing experiments in livestock species. Dr. Greenlee has publications in a number of topic areas including prion agent decontamination, effects of PRNP genotype on susceptibility to the agent of sheep scrapie, characterization of US scrapie strains, transmission of chronic wasting disease to cervids and cattle, features of H-BSE associated with the E211 K polymorphism, and the development of retinal assessment for antemortem screening for prion diseases in sheep and cattle. Dr. Greenlee obtained his DVM degree and completed the PhD/residency program in Veterinary Pathology at Iowa State University. He is a Diplomate of the American College of Veterinary Pathologists.



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...

Discussion

It is clear from all the different aspects of phenotype investigated in this study that one recipient sheep in this experimental transmission expressed a phenotype that was CH1641-like, and different from that of the donor which was diagnosed with atypical scrapie. At present this is a single event, and no conclusion can be drawn about the frequency with which this might happen either experimentally or in the field. With only two animals challenged intracerebrally, and the other recipient remaining negative, it will be impossible to extrapolate whether our finding is truly a stochastic single event, or whether a larger group size would have revealed a trend. The very small group size was an inevitable consequence of the practical limitations of this study given the decision to use only naturally-occurring field case donors, for which material is often sparse and frequently of very poor quality. However, this study provides evidence for the view that conversion/mutation of TSE strains is possible and, irrespective of whether or not such events are stochastic, they can lead to the emergence of potentially zoonotic strains.

There are a number of hypothetical explanations for this unexpected result. The first possibility that had to be excluded was that cross contamination with a CH1641 isolate might have occurred at some point in the experimental procedure. The inoculum was prepared and divided into aliquots on the day of preparation; sheep and mice were challenged using different aliquots of the same homogenate. The only strain identified in mice was atypical scrapie, which was compatible with the diagnosis in the original donor. In addition CH1641 had only been handled by the inoculum preparation team once, two years prior to the inocula for this experiment being prepared, arguing against cross contamination during the preparation of the inoculum. Therefore any possible cross contamination would have had to occur during the inoculation procedure. However, on the inoculation day no CH1641 was handled in the operating theatre—only atypical scrapie, and sterile disposable surgical equipment was used wherever possible and reusable equipment was decontaminated according to strict criteria (one hour immersion in 2M NaOH, followed by autoclaving for 18 mins at 136°C). Additionally, an audit of all prepared CH1641 samples indicated that all the anticipated samples remain in our archive and could not, therefore, have been used in error.

Another possible hypothesis is that the donor sheep might have been co-infected sub-clinically with a CH1641-like classical scrapie strain in addition to atypical scrapie. Such co-infection of different scrapie strains, while observed very rarely, has already been described in field situations [23,37], and in the laboratory context, there is supporting evidence for some heterogeneity of strain populations [38] which may then propagate differently in different hosts.

Since the donor animal was an ARR/ARR genotype, this would further reduce the likelihood of a classical scrapie strain co-existing in this sheep, since there are only two confirmed cases of classical scrapie occurring naturally in this genotype [39]. Alternatively, it could be argued that a resistant sheep could potentially be more likely to harbour low levels of a classical scrapie strain which could remain below detection levels of the currently available laboratory tests, given that little is understood about the fundamental basis for genetic resistance. However, surveillance records were reviewed for details relating to the source flock, and there has been no recorded occurrence of classical scrapie in any genotype of animal from this flock, at any time.

The third, and arguably the most plausible, explanation is that the original atypical isolate has ‘converted/mutated’ into CH1641 as a result of the experimental conditions. Again there is some precedent for this occurrence, with previous experimental observations in porcine transgenic mice, where an atypical scrapie isolate acquired a typical 3-band blot pattern with characteristics similar to sub-passaged ovine BSE [40]. This example relates to a cross-species transmission, but evidence also exists of a bovine isolate ‘converting’ or splitting in PRNP congenic TgBov mice [26]. If this was to occur in the field it could be speculated that a country such as Portugal, in which, for several years, atypical scrapie was reported in the absence of any classical scrapie, would be a good place to look for evidence of this kind of strain conversion. However, none of the few recently reported classical scrapie cases in Portugal were CH1641- like [41]. Under natural conditions, and assuming that the atypical scrapie agent is shed into the environment at all, animals are most likely exposed to only very small quantities of the agent, over a prolonged period of time, and probably by the oral route. In contrast, in the current study, a significant amount of the agent was inoculated directly to the brain thereby bypassing all potential natural physiological barriers to the disease. This may have put a greater pressure on the agent to propagate and evolve leading to the observed strain conversion. The difference of genotype between donor and recipient sheep may also have contributed to this, although this did not affect the retention of the atypical phenotype in the animal which succumbed to the oral challenge.

It is likely that it will never be possible to determine conclusively what gave rise to this change in phenotype. However, this study adds to the growing body of data which highlights a fundamental problem with prion diseases; in the absence of an agent that is structurally independent form the host genome and which can be isolated and typed, classification of natural disease relies on the phenotypic characteristics of the host. Given that some isolates appear to be unstable under certain circumstances, there is a danger in making assumptions about the disease situation in the field, and the associated public and animal health risks based on observed phenotype alone.

Supporting Information S1 File. Clinical signs of recipient animal with CH1641 scrapie. A clinical examination carried out at 514 days post inoculation reveals a bilaterally absent menace response: the sheep does not blink in response to movement of a hand/finger towards the eye but blinks when the skin surrounding the eye is touched with artery forceps. Hind limb ataxia is present (excessive swaying of the hind limbs and awkward placement of the limbs when it moves in the corner of the corridor). It bumps its head against the corner of one of the food troughs protruding into the corridor when it turns and also moves once with its head very close to the food trough after it walks from the corner towards the camera, which suggests some visual impairment. It is however able to negotiate obstacles placed on the floor of the corridor without difficulty. Camera surveillance of the pen showed abnormal lying down and rising behaviour of this sheep (identifiable by the orange arrow) compared to its pen mates (identifiable by the white circle). (MOV) 



Title: Strain typing of U.S. scrapie strains using a panel of inbred mice 

Author item Greenlee, Justin item Kunkle, Robert item Nicholson, Eric item Hamir, Amirali item Bulgin, Marie item Richt, Juergen Submitted to: American College of Veterinary Pathologists Meeting Publication Type: Abstract Only Publication Acceptance Date: 7/15/2008 Publication Date: 11/15/2009 Citation: Greenlee, J.J., Kunkle, R.A., Nicholson, E.M., Hamir, A.N., Bulgin, M.S., Richt, J. 2009. 

Strain Typing of U.S. Scrapie Strains Using a Panel of Inbred Mice [abstract]. 

American College of Veterinary Pathologists. Paper No. 121. p. 762. 

Interpretive Summary:


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.


Molecular Behaviors of “CH1641-Like” Sheep Scrapie Isolates in Ovine Transgenic Mice (TgOvPrP4)▿

 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



MONDAY, MARCH 21, 2011 

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



MONDAY, NOVEMBER 16, 2015 

Docket No. APHIS-2007-0127 Scrapie in Sheep and Goats Terry Singeltary Sr. Submission




Evaluation of the Human Transmission Risk of an Atypical Bovine Spongiform Encephalopathy Prion Strain▿ 

Qingzhong Kong1,*, Mengjie Zheng1, Cristina Casalone2, Liuting Qing1,Shenghai Huang1,†, Bikram Chakraborty1, Ping Wang1, Fusong Chen1,Ignazio Cali1, Cristiano Corona2, Francesca Martucci2, Barbara Iulini2,Pierluigi Acutis2, Lan Wang1, Jingjing Liang1, Meiling Wang1, Xinyi Li1,Salvatore Monaco3, Gianluigi Zanusso3, Wen-Quan Zou1, Maria Caramelli2 andPierluigi Gambetti1,* +Author Affiliations

1Department of Pathology, Case Western Reserve University, Cleveland, Ohio 44106 2CEA, Istituto Zooprofilattico Sperimentale, 10154 Torino, Italy 3Department of Neurological and Visual Sciences, University of Verona, 37134 Verona, Italy Next Section ABSTRACT

Bovine spongiform encephalopathy (BSE), the prion disease in cattle, was widely believed to be caused by only one strain, BSE-C. BSE-C causes the fatal prion disease named new variant Creutzfeldt-Jacob disease in humans. Two atypical BSE strains, bovine amyloidotic spongiform encephalopathy (BASE, also named BSE-L) and BSE-H, have been discovered in several countries since 2004; their transmissibility and phenotypes in humans are unknown. We investigated the infectivity and human phenotype of BASE strains by inoculating transgenic (Tg) mice expressing the human prion protein with brain homogenates from two BASE strain-infected cattle. Sixty percent of the inoculated Tg mice became infected after 20 to 22 months of incubation, a transmission rate higher than those reported for BSE-C. A quarter of BASE strain-infected Tg mice, but none of the Tg mice infected with prions causing a sporadic human prion disease, showed the presence of pathogenic prion protein isoforms in the spleen, indicating that the BASE prion is intrinsically lymphotropic. The pathological prion protein isoforms in BASE strain-infected humanized Tg mouse brains are different from those from the original cattle BASE or sporadic human prion disease. Minimal brain spongiosis and long incubation times are observed for the BASE strain-infected Tg mice. 

***These results suggest that in humans, the BASE strain is a more virulent BSE strain and likely lymphotropic.


 
PPo2-26:

Transmission of Classical and Atypical (L-type) Bovine Spongiform Encephalopathy (BSE) Prions to Cynomolgus macaques

Fumiko Ono,1 Yoshio Yamakawa,2 Minoru Tobiume,3 Yuko Sato,3 Harutaka Katano,3 Kenichi Hagiwara,2 Iori Itagaki,1 Akio Hiyaoka,1 Katuhiko Komatuzaki,1 Yasunori Emoto,1 Hiroaki Shibata,4 Yuichi Murayama,5 Keiji Terao,4 Yasuhiro Yasutomi4 and Tetsutaro Sata3

1The Corporation for Production and Research of Laboratory Primates; Tsukuba City, Japan; 2Departments of Cell Biology and Biochemistry; and 3Pathology; National Institute of Infectious Diseases; Tokyo, Japan; 4Tsukuba Primate Research Center; National Institute of Biomedical Innovation; Tsukuba City, Japan; 5Prion Disease Research Team; National Institute of Animal Health; Tsukuba City, Japan

Key words: L-type BSE, cBSE, cynomolgus macaques, transmission

BSE prion derived from classical BSE (cBSE) or L-type BSE was characterized by inoculation into the brain of cynomolgus macaques. The neurologic manifestation was developed in all cynomolgus macaques at 27–43 months after intracerebral inoculation of brain homogenate from cBSE-affected cattle (BSE JP/6). Second transmission of cBSE from macaque to macaque shortened incubation period to 13–18 months. cBSE-affected macaques showed the similar clinical signs including hyperekplexia, tremor and paralysis in both primary and second transmission.

Two macaques were intracerebrally inoculated brain homogenate from the L-type BSE-affected cattle (BSE JP/24). The incubation periods were 19–20 months in primary transmission.

The clinical course of the L-type BSE-affected macaques differed from that in cBSE-affected macaques in the points of severe myoclonus without hyperekplexia. 

The glycoform profile of PrPSc detected in macaque CNS was consistent with original pattern of either cBSE or L-typeBSE PrPSc, respectively. 

Although severe spongiform change in the brain was remarkable in all BSE-affected macaques, severe spongiform spread widely in cerebral cortex in L-type BSE-affected macaques. 

Heavy accumulation of PrPSc surrounded by vacuola formed florid plaques in cerebral cortex of cBSE-affected macaques. 

Deposit of PrPSc in L-type BSE-affected macaque was weak and diffuse synaptic pattern in cerebrum, but large PrPSc plaques were evident at cerebellum. 

MRI analysis, T2, T1, DW and flair sequences, at the time of autopsy revealed that brain atrophy and dilatation of cerebral ventricles were significantly severe in L-type BSE-affected macaques. 

***These results suggest that L-type BSE is more virulent strain to primates comparing to cBSE.


 Atypical BSE (BASE) Transmitted from Asymptomatic Aging Cattle to a Primate

Emmanuel E. Comoy1*, Cristina Casalone2, Nathalie Lescoutra-Etchegaray1, Gianluigi Zanusso3, Sophie Freire1, Dominique Marcé1, Frédéric Auvré1, Marie-Magdeleine Ruchoux1, Sergio Ferrari3, Salvatore Monaco3, Nicole Salès4, Maria Caramelli2, Philippe Leboulch1,5, Paul Brown1, Corinne I. Lasmézas4, Jean-Philippe Deslys1

1 Institute of Emerging Diseases and Innovative Therapies, CEA, Fontenay-aux-Roses, France, 2 Istituto Zooprofilattico Sperimentale del Piemonte, Turin, Italy, 3 Policlinico G.B. Rossi, Verona, Italy, 4 Scripps Florida, Jupiter, Florida, United States of America, 5 Genetics Division, Brigham & Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America

Abstract Top Background Human variant Creutzfeldt-Jakob Disease (vCJD) results from foodborne transmission of prions from slaughtered cattle with classical Bovine Spongiform Encephalopathy (cBSE). 

***Atypical forms of BSE, which remain mostly asymptomatic in aging cattle, were recently identified at slaughterhouses throughout Europe and North America, raising a question about human susceptibility to these new prion strains.

Methodology/Principal Findings Brain homogenates from cattle with classical BSE and atypical (BASE) infections were inoculated intracerebrally into cynomolgus monkeys (Macacca fascicularis), a non-human primate model previously demonstrated to be susceptible to the original strain of cBSE. The resulting diseases were compared in terms of clinical signs, histology and biochemistry of the abnormal prion protein (PrPres). 

***The single monkey infected with BASE had a shorter survival, and a different clinical evolution, histopathology, and prion protein (PrPres) pattern than was observed for either classical BSE or vCJD-inoculated animals. 

***Also, the biochemical signature of PrPres in the BASE-inoculated animal was found to have a higher proteinase K sensitivity of the octa-repeat region. 

***We found the same biochemical signature in three of four human patients with sporadic CJD and an MM type 2 PrP genotype who lived in the same country as the infected bovine.

*** Conclusion/Significance Our results point to a possibly higher degree of pathogenicity of BASE than classical BSE in primates and also raise a question about a possible link to one uncommon subset of cases of apparently sporadic CJD. 

***Thus, despite the waning epidemic of classical BSE, the occurrence of atypical strains should temper the urge to relax measures currently in place to protect public health from accidental contamination by BSE-contaminated products.

Citation: Comoy EE, Casalone C, Lescoutra-Etchegaray N, Zanusso G, Freire S, et al. (2008) Atypical BSE (BASE) Transmitted from Asymptomatic Aging Cattle to a Primate. PLoS ONE 3(8): e3017. doi:10.1371/journal.pone.0003017

Editor: Neil Mabbott, University of Edinburgh, United Kingdom

Received: April 24, 2008; Accepted: August 1, 2008; Published: August 20, 2008

Copyright: © 2008 Comoy et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Funding: This work has been supported by the Network of Excellence NeuroPrion.

Competing interests: CEA owns a patent covering the BSE diagnostic tests commercialized by the company Bio-Rad.

* E-mail: emmanuel.comoy@cea.fr


 Session I - Prions: Structure, Strain and Detection (II)

Searching for BASE Strain Signature in Sporadic Creutzfedlt-Jakob Disease

Gianluigi Zanusso

Department of Neurological and Visual Sciences, Section of Clinical Neurology University of Verona, Verona, Italy.

Bovine amyloidotic spongiform encephalopathy (BASE) is a newly recognized form of bovine prion disease, which was originally detected in Italy in 2004 as an effect of active surveillance. BASE or BSE L-type (L is referred to the lower electrophoretic PrPSc migration than classical BSE) has now been reported in several countries, including Japan. 

All field cases of BASE were older than 8 years and neurologically normal at the time of slaughtered. By experimental transmission, we defined the disease phenotype of cattle BASE, which is quite distinct from that seen in typical BSE and characterized by mental dullness and amyotrophy. 

Surprisingly, following intraspecies and interspecies transmission the incubation period of BASE was shorter than BSE. 

***The relatively easy transmission of BASE isolate as well as the molecular similarity with sporadic Creutzfeldt-Jakob disease (sCJD) have raised concern regarding its potential passage to humans. Tg humanized mice Met/Met at codon 129 challenged with both BSE and BASE isolates, showed a resistance to BSE but a susceptibility to BASE at a 60% rate; in addition, BASE-inoculated Cynomolgus (129 Met/Met) had shorter incubation periods than BSE-inoculated primates. 

In this study we compared the biochemical properties of PrPSc in Cynomolgus and in TgHu Met/Met mice challenged with BSE and BASE strains, by conventional SDS-PAGE analysis and 2D separation. The results obtained disclose distinct conformational changes in PrPSc, which are dependent on the inoculated host but not on the codon 129 genotype.

This work was supported by Neuroprion contract n. FOOD CT 2004 -506579 (NOE)


P.150: Zoonotic potential of L-type BSE prions: A new prion disease in humans?

Emilie Jaumain,1 Stéphane Haïk,2 Isabelle Quadrio,3 Laetitia Herzog,1 Fabienne Reine,1 Armand Perret-Liaudet,3 Human Rezaei,1 Hubert Laude,1 Jean-Luc Vilotte,4 and Vincent Béringue1 1INR A (Institut National de la Recherche Agronomique); UR892; Virologie Immunologie Moléculaires; Jouy-en-Josas, France; 2IN SERM; Equipe maladie d’Alzheimer et maladies à Prions; CRicm; UMRS 1127; CNR S; UPMC. R.; ICM, Hôpital de la Salpêtrière; Paris, France; 3Neurobiologie, CMRR , Gériatrie, Hospices Civils de Lyon, Université Lyon 1-CNR S UMR5292-IN SERM U1028; Lyon, France; 3INR A; UMR1313; Génétique Animale et Biologie Intégrative; Jouy-en-Josas, France

Two novel prion strains, referred to as BSE-L and BSE-H, have been recognized in bovines through active prion surveillance programs, both being distinct from the epizootic, ‘classical’, BSE strain (C-BSE). Both H and L-types have been detected worldwide as rare cases occurring in aged animals. Like C-BSE prions, H- and L-types prions can propagate with relative ease in foreign species or in transgenic mouse lines expressing heterologous PrP sequences. A prion exhibiting biological properties similar to C-BSE agent sometimes emerged from these cross-species transmissions. 

***Previously, L-type prions were shown to transmit to transgenic mice expressing human PrP with methionine at codon 129 with higher efficacy than C-BSE prions. 

Here, we examined whether L-type prions propagate without any apparent transmission barrier in these mice and whether such ‘humanised’ L-type prions share biological properties with CJD prions. 

L-type prions and a panel of human CJD cases with various genotypes at codon 129 and electrophoretic PrPres signatures were serially transmitted by intracerebral route to human PrP mice. 

The biological phenotypes induced by these agents were compared by all the standard methods currently used to distinguish between prion strains. 

***At each passage, L-type prions were also transmitted back to bovine PrP mice to assess whether the agent has evolved upon passaging on the human PrP sequence. L-type prions transmitted to human PrP mice at 100% attack rate, without notable alteration in the mean incubation times over 5 passages. 

***At each passage, ‘humanized’ L-type prions were able to transmit back to bovine PrP transgenic mice without apparent transmission barrier, as based on the survival time and the restoration of a L-type BSE phenotype. 

*** Comparison of mean incubation times on primary and subsequent passages in human PrP mice showed no overlap between L-type and sporadic CJD agents. 

*** While the electrophoretic signature and regional distribution of PrPres in L-type diseased mouse brains resembled that seen after transmission of MM2 CJD strain type, both agents exhibited distinct resistance of the associated PrPres molecules to protease denaturation.

*** In summary, L-type prions can be passaged on the human PrP sequence without any obvious transmission barrier. The phenotype obtained differs from the classical CJD prion types known so far. Careful extrapolation would suggest that the zoonotic transmission of this agent could establish a new prion disease type in humans.

========Prion2013==========


The present data offer novel information on the tropism of the BASE agent and highlight relevant public health issues. 

***While the transmission barrier for classical BSE is high in most species, BASE prions are readily transmissible to a variety of mammals including non-human primates [11]–[13], [35]. 

***Accordingly, the possibility of spreading of BASE prions through skeletal muscle to other species should be taken into account and evaluated in risk analysis studies.


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. 


2014 

***Moreover, L-BSE has been transmitted more easily to transgenic mice overexpressing a human PrP [13,14] or to primates [15,16] than C-BSE. 

***It has been suggested that some sporadic CJD subtypes in humans may result from an exposure to the L-BSE agent. 

*** Lending support to this hypothesis, pathological and biochemical similarities have been observed between L-BSE and an sCJD subtype (MV genotype at codon 129 of PRNP) [17], and between L-BSE infected non-human primate and another sCJD subtype (MM genotype) [15]. 

snip... 


WEDNESDAY, MARCH 15, 2017 

In vitro amplification of H-type atypical bovine spongiform encephalopathy by protein misfolding cyclic amplification 

"When considering the atypical L-BSE and H-BSE diseases of cattle, they have been assessed in both non-human primate and transgenic mouse bioassays (with mice transgenic for human PRNP) and both model systems indicate that H-BSE and L-BSE may have increased zoonotic potential compare with C-BSE. 

***The detection of all types of BSE is therefore of significant importance." 


SUNDAY, JULY 23, 2017

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


*** Industry should be aware, however, of the implications of sporadic BSE. Its occurrence would necessitate the indefinite retention of all of the public health measures that exclude high-risk bovine tissues from the animal and human food chains, whereas its nonoccurrence would permit tissues that are now destroyed to be used as before, once orally acquired BSE has disappeared.


***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.***


Journal of Wildlife Diseases 50(3):660-665. 2014 https://doi.org/10.7589/2013-10-274

“Atypical” Chronic Wasting Disease in PRNP Genotype 225FF Mule Deer 

Lisa L. Wolfe, Karen A. Fox, and Michael W. Miller Wildlife Disease Association 2014 Received: October 21, 2013; Accepted: January 22, 2014 [+] Author & Article Info

Abstract

We compared mule deer (Odocoileus hemionus) of two different PRNP genotypes (225SS, 225FF) for susceptibility to chronic wasting disease (CWD) in the face of environmental exposure to infectivity. All three 225SS deer had immunohistochemistry (IHC)-positive tonsil biopsies by 710 days postexposure (dpe), developed classic clinical signs by 723–1,200 dpe, and showed gross and microscopic pathology, enzyme-linked immunosorbent assay (ELISA) results, and IHC staining typical of prion disease in mule deer. In contrast, although all three 225FF deer also became infected, the two individuals surviving >720 dpe had consistently negative biopsies, developed more-subtle clinical signs of CWD, and died 924 or 1,783 dpe. The 225FF deer were “suspect” by ELISA postmortem but showed negative or equivocal IHC staining of lymphoid tissues; both clinically affected 225FF deer had spongiform encephalopathy in the absence of IHC staining in the brain tissue. The experimental cases resembled three cases encountered among five additional captive 225FF deer that were not part of our experiment but also died from CWD. Aside from differences in clinical disease presentation and detection, 225FF mule deer also showed other, more-subtle, atypical traits that may help to explain the rarity of this genotype in natural populations, even in the presence of enzootic CWD.



P35

ADAPTATION OF CHRONIC WASTING DISEASE (CWD) INTO HAMSTERS, EVIDENCE OF A WISCONSIN STRAIN OF CWD

Chad Johnson1, Judd Aiken2,3,4 and Debbie McKenzie4,5 1 Department of Comparative Biosciences, University of Wisconsin, Madison WI, USA 53706 2 Department of Agriculture, Food and Nutritional Sciences, 3 Alberta Veterinary Research Institute, 4.Center for Prions and Protein Folding Diseases, 5 Department of Biological Sciences, University of Alberta, Edmonton AB, Canada T6G 2P5 The identification and characterization of prion strains is increasingly important for the diagnosis and biological definition of these infectious pathogens. Although well-established in scrapie and, more recently, in BSE, comparatively little is known about the possibility of prion strains in chronic wasting disease (CWD), a disease affecting free ranging and captive cervids, primarily in North America. We have identified prion protein variants in the white-tailed deer population and demonstrated that Prnp genotype affects the susceptibility/disease progression of white-tailed deer to CWD agent. The existence of cervid prion protein variants raises the likelihood of distinct CWD strains. Small rodent models are a useful means of identifying prion strains. We intracerebrally inoculated hamsters with brain homogenates and phosphotungstate concentrated preparations from CWD positive hunter-harvested (Wisconsin CWD endemic area) and experimentally infected deer of known Prnp genotypes. These transmission studies resulted in clinical presentation in primary passage of concentrated CWD prions. Subclinical infection was established with the other primary passages based on the detection of PrPCWD in the brains of hamsters and the successful disease transmission upon second passage. Second and third passage data, when compared to transmission studies using different CWD inocula (Raymond et al., 2007) indicate that the CWD agent present in the Wisconsin white-tailed deer population is different than the strain(s) present in elk, mule-deer and white-tailed deer from the western United States endemic region.


FRIDAY, MAY 14, 2010 

Prion Strain Mutation Determined by Prion Protein Conformational Compatibility and Primary Structure


MONDAY, JANUARY 09, 2017 

Oral Transmission of L-Type Bovine Spongiform Encephalopathy Agent among Cattle 

CDC Volume 23, Number 2—February 2017 

*** Consumption of L-BSE–contaminated feed may pose a risk for oral transmission of the disease agent to cattle.

Volume 23, Number 2—February 2017

Dispatch

Oral Transmission of L-Type Bovine Spongiform Encephalopathy Agent among Cattle

Abstract

To determine oral transmissibility of the L-type bovine spongiform encephalopathy (BSE) prion, we orally inoculated 16 calves with brain homogenates of the agent. Only 1 animal, given a high dose, showed signs and died at 88 months. These results suggest low risk for oral transmission of the L-BSE agent among cattle.

The epidemic of bovine spongiform encephalopathy (BSE) in cattle is thought to be caused by oral infection through consumption of feed containing the BSE agent (prion). Since 2003, different neuropathologic and molecular phenotypes of BSE have been identified as causing ≈110 cases of atypical BSE worldwide, mainly in aged cattle. Although the etiology and pathogenesis of atypical BSE are not yet fully understood, atypical BSE prions possibly cause sporadic cases of BSE (1).

The L-type BSE prion (L-BSE) has been experimentally transmitted to cattle by intracerebral challenge, and the incubation period was is shorter than that for classical BSE (C-BSE) prions (2–6). The origin of transmissible mink encephalopathy in ranch-raised mink is thought to be caused by ingestion of L-BSE–infected material (7). Although L-BSE has been orally transmitted to mouse lemurs (8), it remains to be established whether L-BSE can be transmitted to cattle by oral infection. We therefore investigated the transmissibility of L-BSE by the oral route and tissue distribution of disease-associated prion protein (PrPSc) in cattle. All experiments involving animals were performed with the approval of the Animal Ethical Committee and the Animal Care and Use Committee of the National Institute of Animal Health (approval nos. 07–88 and 08–010).

The Study

We divided a group of 16 Holstein female calves, 3–5 months of age, into 4 groups of 2–6 animals each. Each group of calves was orally administered 1 g (n = 4), 5 g (n = 6), 10 g (n = 4), or 50 g (n = 2) of pooled whole-brain homogenate prepared from cattle experimentally infected with L-BSE (3,6) (Table(https://wwwnc.cdc.gov/eid/article/23/2/16-1416-t1)). The endpoint titer of the pooled brain homogenate assayed in bovinized transgenic (TgBoPrP) mice was 106.9 of 50% lethal dose/g tissue (data not shown). As noninfected controls, 3 female calves were obtained at 3–4 months of age and euthanized at 60, 92, and 103 months of age, and samples were analyzed as for the experimental animals.

At 88 months after inoculation, 1 of the animals (91 months of age) that had received 50 g of L-BSE–infected brain homogenate was unable to get up. The animal extended her forelimbs and hind limbs rigidly forward but did not show persistent knuckling of her fetlock; she did not have difficulty eating and drinking. Seven days after appearance of clinical signs, the animal was found dead, having shown no characteristic signs of L-BSE, such as dullness, lowering of the head, and overreactivity to external stimuli, which had previously been observed after intracerebral inoculation of animals under experimental conditions (4).

Histopathologic examination of tissues from this animal revealed minimal or mild spongiform changes of the gray matter neuropil in the thalamic and brainstem nuclei; however, these changes were not visible in the cerebral and cerebellar cortices, the olfactory bulb, or the dorsal motor nucleus of the vagus nerve at the obex. Higher amounts of proteinase K–resistant PrPSc, analyzed by Western blotting with monoclonal antibody T2 (9), were detected in the thalamus, brainstem, cerebellum, spinal cord, and retina (Figure 1, lanes 8–16; Figures 2, panels A, B), whereas PrPSc accumulation was lower in the cerebral cortices and the olfactory bulb (Figure 1, lanes 1–6). The molecular characteristics of proteinase K–resistant PrPSc, such as the molecular weight and the glycoform profile in the brain of the animal, were identical to those observed in the inoculum. The most conspicuous PrPSc finding, obtained by using immunohistochemistry with monoclonal antibody F99/97.6.1 (VMRD, Pullman, WA, USA), was fine and coarse granular deposits in the neuropil of the thalamus, brainstem, and gray matter of the spinal cord, and in the retina. Perineuronal PrPSc staining was conspicuous in the large neurons of the thalamic and brainstem nuclei (Figure 2, panel C) but less common in other brain areas. Fewer PrPSc deposits were dispersed in the dorsal motor nucleus of the vagus nerve at the obex (Figure 2, panel A). No amyloid plaques were detectable in any brain section. In the extracerebral tissues, PrPSc was lower in most of the samples from the nerve ganglia (trigeminal, dorsal root, stellate, cervical cranial, nodose, and celiac and mesenteric), cauda equina, vagal nerve, optic nerve, neurohypophysis, ocular muscle, and adrenal medulla (Figure 1, lanes 17–33; Figures 2, panels D–H). However, no PrPSc signal was detected in most of the somatic nerve fibers (Figure 1, lanes 25, 26, 29, 30), the enteric nervous system (Figure 1, lanes 32, 33), and any lymphoid organs including the remaining Peyer’s patches (data not shown).

The only other animal inoculated with 50 g of L-BSE brain material was alive and clinically healthy as of postinoculation month 94 (December 2016). Calves that received 1 g, 5 g, or 10 g of L-BSE brain tissues showed no clinical signs of BSE and were euthanized and underwent necropsy 51–86 months after inoculation (Table(https://wwwnc.cdc.gov/eid/article/23/2/16-1416-t1)). For all of these animals and the uninfected controls, PrPSc results were negative by Western blot and immunohistochemical analysis.

Conclusions

Our results suggest that the risk for oral transmission of L-BSE among cattle may be very low; after 88 months, the only case of transmission occurred in a cow that had been inoculated with a high dose of L-BSE–infected brain homogenate. The incubation period was much longer for cattle dosed orally with L-BSE–infected brain homogenate than for cattle dosed orally with C-BSE–infected tissue (34−74 mo for C-BSE) (10). This finding may suggest that the L-BSE prion requires much longer to propagate from the gut to the central nervous system. In addition, the lack of clinical signs, except for difficulty in rising, may present a genuine clinical picture of L-BSE under natural conditions (11). In most cases of naturally occurring atypical BSE identified so far, the animals were >8 years of age, except for 3 cases: 1 H-BSE and 1 L-BSE in Spain (1) and 1 H-BSE in Germany (12). Therefore, we cannot exclude the possibility that L-BSE developed sporadically/spontaneously. However, this case may not have naturally occurred, in view of the low prevalence of L-BSE in Japan during October 2001–August 2016, which was 0.065 cases/1 million tested adult animals. In our study, the remaining live animal, challenged with 50 g of L-BSE brain homogenate, will provide the further information about the oral transmissibility to cattle. Bioassays of brain samples in TgBoPrP mice are ongoing.

The neuroanatomical PrPSc distribution pattern of orally challenged cattle differed somewhat from that described in cattle naturally and intracerebrally challenged with L-BSE (2–6,11,13,14), The conspicuous differences between the case we report and cases of natural and experimental infection are 1) higher amounts of PrPSc in the caudal medulla oblongata and the spinal cord coupled with that in the thalamus and the more rostral brainstem and 2) relatively low amounts of PrPSc in the cerebral cortices and the olfactory bulb. Furthermore, fewer PrPSc deposits in the dorsal motor nucleus of the vagus nerve may indicate that the parasympathetic retrogressive neuroinvasion pathway does not contribute to transport of the L-BSE prion from the gut to the brain, which is in contrast to the vagus-associated transport of the agent in C-BSE (15). PrPSc accumulation in the extracerebral tissues may be a result of centrifugal trafficking of the L-BSE prion from the central nervous system along somatic or autonomic nerve fibers rather than centripetal propagation of the agent (4,6,9). Consumption of L-BSE–contaminated feed may pose a risk for oral transmission of the disease agent to cattle.

Dr. Okada is a veterinary pathologist and chief researcher at the National Institute of Animal Health, National Agriculture and Food Research Organization, Ibaraki, Japan. His research focuses on the pathogenesis of animal prion diseases in ruminants as natural hosts and in experimentally infected animals.

Acknowledgments

We thank Naoko Tabeta, Naomi Furuya, Junko Yamada, Ritsuko Miwa, Noriko Shinozaki, and the animal caretakers for their expert technical assistance.

This work was supported by grants-in-aid from the BSE and Other Prion Disease project and the Improving Food Safety and Animal Health project of the Ministry of Agriculture, Forestry and Fisheries, Japan.

References


***********OCTOBER 2015*************

*** PRION 2015 ORAL AND POSTER CONGRESSIONAL ABSTRACTS ***

THANK YOU PRION 2015 TAYLOR & FRANCIS, Professor Chernoff, and Professor Aguzzi et al, for making these PRION 2015 Congressional Poster and Oral Abstracts available freely to the public. ...Terry S. Singeltary Sr.

P.108: Successful oral challenge of adult cattle with classical BSE

Sandor Dudas1,*, Kristina Santiago-Mateo1, Tammy Pickles1, Catherine Graham2, and Stefanie Czub1 1Canadian Food Inspection Agency; NCAD Lethbridge; Lethbridge, Alberta, Canada; 2Nova Scotia Department of Agriculture; Pathology Laboratory; Truro, Nova Scotia, Canada

Classical Bovine spongiform encephalopathy (C-type BSE) is a feed- and food-borne fatal neurological disease which can be orally transmitted to cattle and humans. Due to the presence of contaminated milk replacer, it is generally assumed that cattle become infected early in life as calves and then succumb to disease as adults. Here we challenged three 14 months old cattle per-orally with 100 grams of C-type BSE brain to investigate age-related susceptibility or resistance. During incubation, the animals were sampled monthly for blood and feces and subjected to standardized testing to identify changes related to neurological disease. At 53 months post exposure, progressive signs of central nervous system disease were observed in these 3 animals, and they were euthanized. Two of the C-BSE animals tested strongly positive using standard BSE rapid tests, 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. 

***Our study demonstrates susceptibility of adult cattle to oral transmission of classical BSE. 

We are further examining explanations for the unusual disease presentation in the third challenged animal.


***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.

P.86: Estimating the risk of transmission of BSE and scrapie to ruminants and humans by protein misfolding cyclic amplification

Morikazu Imamura, Naoko Tabeta, Yoshifumi Iwamaru, and Yuichi Murayama National Institute of Animal Health; Tsukuba, Japan

To assess the risk of the transmission of ruminant prions to ruminants and humans at the molecular level, we investigated the ability of abnormal prion protein (PrPSc) of typical and atypical BSEs (L-type and H-type) and typical scrapie to convert normal prion protein (PrPC) from bovine, ovine, and human to proteinase K-resistant PrPSc-like form (PrPres) using serial protein misfolding cyclic amplifi- cation (PMCA).

Six rounds of serial PMCA was performed using 10% brain homogenates from transgenic mice expressing bovine, ovine or human PrPC in combination with PrPSc seed from typical and atypical BSE- or typical scrapie-infected brain homogenates from native host species. In the conventional PMCA, the conversion of PrPC to PrPres was observed only when the species of PrPC source and PrPSc seed matched. However, in the PMCA with supplements (digitonin, synthetic polyA and heparin), both bovine and ovine PrPC were converted by PrPSc from all tested prion strains. On the other hand, human PrPC was converted by PrPSc from typical and H-type BSE in this PMCA condition.

Although these results were not compatible with the previous reports describing the lack of transmissibility of H-type BSE to ovine and human transgenic mice, 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.


P.170: Potential detection of oral transmission of H type atypical BSE in cattle using in vitro conversion

***P.170: Potential detection of oral transmission of H type atypical BSE in cattle using in vitro conversion

Sandor Dudas, John G Gray, Renee Clark, and Stefanie Czub Canadian Food Inspection Agency; Lethbridge, AB Canada

Keywords: Atypical BSE, oral transmission, RT-QuIC

The detection of bovine spongiform encephalopathy (BSE) has had a significant negative impact on the cattle industry worldwide. In response, governments took actions to prevent transmission and additional threats to animal health and food safety. While these measures seem to be effective for controlling classical BSE, the more recently discovered atypical BSE has presented a new challenge. To generate data for risk assessment and control measures, we have challenged cattle orally with atypical BSE to determine transmissibility and mis-folded prion (PrPSc) tissue distribution. Upon presentation of clinical symptoms, animals were euthanized and tested for characteristic histopathological changes as well as PrPSc deposition.

The H-type challenged animal displayed vacuolation exclusively in rostral brain areas but the L-type challenged animal showed no evidence thereof. To our surprise, neither of the animals euthanized, which were displaying clinical signs indicative of BSE, showed conclusive mis-folded prion accumulation in the brain or gut using standard molecular or immunohistochemical assays. To confirm presence or absence of prion infectivity, we employed an optimized real-time quaking induced conversion (RT-QuIC) assay developed at the Rocky Mountain Laboratory, Hamilton, USA.

Detection of PrPSc was unsuccessful for brain samples tests from the orally inoculated L type animal using the RT-QuIC. It is possible that these negative results were related to the tissue sampling locations or that type specific optimization is needed to detect PrPSc in this animal. We were however able to consistently detect the presence of mis-folded prions in the brain of the H-type inoculated animal. Considering the negative and inconclusive results with other PrPSc detection methods, positive results using the optimized RT-QuIC suggests the method is extremely sensitive for H-type BSE detection. This may be evidence of the first successful oral transmission of H type atypical BSE in cattle and additional investigation of samples from these animals are ongoing.





Wednesday, July 15, 2015

Additional BSE TSE prion testing detects pathologic lesion in unusual brain location and PrPsc by PMCA only, how many cases have we missed?



Saturday, July 23, 2016

BOVINE SPONGIFORM ENCEPHALOPATHY BSE TSE PRION SURVEILLANCE, TESTING, AND SRM REMOVAL UNITED STATE OF AMERICA UPDATE JULY 2016

 

Monday, June 20, 2016 

Specified Risk Materials SRMs BSE TSE Prion Program 



--->CHRONIC WASTING DISEASE CWD TSE PRION REALITY ON THE REAL THREAT OF ZOONOSIS ZOONOTIC DISEASE<--- div="">

2017

Subject: ***CDC Now Recommends Strongly consider having the deer or elk tested for CWD before you eat the meat

CDC Now Recommends Strongly consider having the deer or elk tested for CWD before you eat the meat 

Chronic Wasting Disease (CWD) 

Prevention 

If CWD could spread to people, it would most likely be through eating of infected deer and elk. In a 2006-2007 CDC survey of U.S. residents, nearly 20 percent of those surveyed said they had hunted deer or elk and more than two-thirds said they had eaten venison or elk meat. However, to date, no CWD infections have been reported in people. 

Hunters must consider many factors when determining whether to eat meat from deer and elk harvested from areas with CWD, including the level of risk they are willing to accept. Hunters harvesting wild deer and elk from areas with reported CWD should check state wildlife and public health guidance to see whether testing of animals is recommended or required in a given state or region. In areas where CWD is known to be present, CDC recommends that hunters strongly consider having those animals tested before eating the meat. 

Tests for CWD are monitoring tools that some state wildlife officials use to look at the rates of CWD in certain animal populations. Testing may not be available in every state, and states may use these tests in different ways. A negative test result does not guarantee that an individual animal is not infected with CWD, but it does make it considerably less likely and may reduce your risk of exposure to CWD. 

To be as safe as possible and decrease their potential risk of exposure to CWD, hunters should take the following steps when hunting in areas with CWD: 

Do not shoot, handle or eat meat from deer and elk that look sick or are acting strangely or are found dead (road-kill). When field-dressing a deer: Wear latex or rubber gloves when dressing the animal or handling the meat. Minimize how much you handle the organs of the animal, particularly the brain or spinal cord tissues. Do not use household knives or other kitchen utensils for field dressing. Check state wildlife and public health guidance to see whether testing of animals is recommended or required. Recommendations vary by state, but information about testing is available from many state wildlife agencies. Strongly consider having the deer or elk tested for CWD before you eat the meat. If you have your deer or elk commercially processed, consider asking that your animal be processed individually to avoid mixing meat from multiple animals. If your animal tests positive for CWD, do not eat meat from that animal. The U.S. Department of Agriculture’s Animal and Plant Health Inspection Service regulates commercially farmed deer and elk. The agency operates a national CWD herd certification program. As part of the voluntary program, states and individual herd owners agree to meet requirements meant to decrease the risk of CWD in their herds. Privately owned herds that do not participate in the herd certification program may be at increased risk for CWD. 

Page last reviewed: August 17, 2017 Page last updated: August 17, 2017 Content source: Centers for Disease Control and Prevention National Center for Emerging and Zoonotic Infectious Diseases (NCEZID) Division of High-Consequence Pathogens and Pathology (DHCPP) 


 > 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).*** 



Molecular Barriers to Zoonotic Transmission of Prions 

*** chronic wasting disease, there was no absolute barrier to conversion of the human prion protein. 

*** 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. 


TUESDAY, SEPTEMBER 12, 2017 

CDC Now Recommends Strongly consider having the deer or elk tested for CWD before you eat the meat 


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


TUESDAY, JULY 04, 2017

*** PRION 2017 CONFERENCE ABSTRACTS ON CHRONIC WASTING DISEASE CWD TSE PRION ***


TUESDAY, JUNE 13, 2017

PRION 2017 CONFERENCE ABSTRACT Chronic Wasting Disease in European moose is associated with PrPSc features different from North American CWD


Wednesday, May 24, 2017 

PRION2017 CONFERENCE VIDEO UPDATE 23 – 26 May 2017 Edinburgh UPDATE 1 


SATURDAY, JULY 29, 2017 

Risk Advisory Opinion: Potential Human Health Risks from Chronic Wasting Disease CFIA, PHAC, HC (HPFB and FNIHB), INAC, Parks Canada, ECCC and AAFC 


Prion Infectivity in Fat of Deer with Chronic Wasting Disease▿ 

Brent Race#, Kimberly Meade-White#, Richard Race and Bruce Chesebro* + Author Affiliations

Rocky Mountain Laboratories, 903 South 4th Street, Hamilton, Montana 59840 Next Section ABSTRACT

Chronic wasting disease (CWD) is a neurodegenerative prion disease of cervids. Some animal prion diseases, such as bovine spongiform encephalopathy, can infect humans; however, human susceptibility to CWD is unknown. In ruminants, prion infectivity is found in central nervous system and lymphoid tissues, with smaller amounts in intestine and muscle. In mice, prion infectivity was recently detected in fat. Since ruminant fat is consumed by humans and fed to animals, we determined infectivity titers in fat from two CWD-infected deer. Deer fat devoid of muscle contained low levels of CWD infectivity and might be a risk factor for prion infection of other species.


Prions in Skeletal Muscles of Deer with Chronic Wasting Disease 

Rachel C. Angers1,*, Shawn R. Browning1,*,†, Tanya S. Seward2, Christina J. Sigurdson4,‡, Michael W. Miller5, Edward A. Hoover4, Glenn C. Telling1,2,3,§ ↵* These authors contributed equally to this work. ↵† Present address: Department of Infectology, Scripps Research Institute, 5353 Parkside Drive, RF-2, Jupiter, FL 33458, USA. ↵‡ Present address: Institute of Neuropathology, University of Zurich, Schmelzbergstrasse 12, 8091 Zurich, Switzerland. + See all authors and affiliations Science 24 Feb 2006: Vol. 311, Issue 5764, pp. 1117 DOI: 10.1126/science.1122864 Article Figures & Data Info & Metrics eLetters PDF You are currently viewing the abstract.

View Full Text

Abstract

The emergence of chronic wasting disease (CWD) in deer and elk in an increasingly wide geographic area, as well as the interspecies transmission of bovine spongiform encephalopathy to humans in the form of variant Creutzfeldt Jakob disease, have raised concerns about the zoonotic potential of CWD. Because meat consumption is the most likely means of exposure, it is important to determine whether skeletal muscle of diseased cervids contains prion infectivity. 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.



*** 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 


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 


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 ; 


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

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


*** 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. 



BSE INQUIRY

*** 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 ;


you can see more evidence here ;


*** After a natural route of exposure, 100% of WTD were susceptible to scrapie.

PO-039: A comparison of scrapie and chronic wasting disease in white-tailed deer
 
Justin Greenlee, Jodi Smith, Eric Nicholson US Dept. Agriculture; Agricultural Research Service, National Animal Disease Center; Ames, IA USA
 
 
White-tailed deer are susceptible to the agent of sheep scrapie by intracerebral inoculation
 
snip...
 
It is unlikely that CWD will be eradicated from free-ranging cervids, and the disease is likely to continue to spread geographically [10]. However, the potential that white-tailed deer may be susceptible to sheep scrapie by a natural route presents an additional confounding factor to halting the spread of CWD. This leads to the additional speculations that
 
1) infected deer could serve as a reservoir to infect sheep with scrapie offering challenges to scrapie eradication efforts and
 
2) CWD spread need not remain geographically confined to current endemic areas, but could occur anywhere that sheep with scrapie and susceptible cervids cohabitate.
 
This work demonstrates for the first time that white-tailed deer are susceptible to sheep scrapie by intracerebral inoculation with a high attack rate and that the disease that results has similarities to CWD. These experiments will be repeated with a more natural route of inoculation to determine the likelihood of the potential transmission of sheep scrapie to white-tailed deer. If scrapie were to occur in white-tailed deer, results of this study indicate that it would be detected as a TSE, but may be difficult to differentiate from CWD without in-depth biochemical analysis.
 
 
 
2012
 
PO-039: A comparison of scrapie and chronic wasting disease in white-tailed deer
 
Justin Greenlee, Jodi Smith, Eric Nicholson US Dept. Agriculture; Agricultural Research Service, National Animal Disease Center; Ames, IA USA
 
snip...
 
The results of this study suggest that there are many similarities in the manifestation of CWD and scrapie in WTD after IC inoculation including early and widespread presence of PrPSc in lymphoid tissues, clinical signs of depression and weight loss progressing to wasting, and an incubation time of 21-23 months. Moreover, western blots (WB) done on brain material from the obex region have a molecular profile similar to CWD and distinct from tissues of the cerebrum or the scrapie inoculum. However, results of microscopic and IHC examination indicate that there are differences between the lesions expected in CWD and those that occur in deer with scrapie: amyloid plaques were not noted in any sections of brain examined from these deer and the pattern of immunoreactivity by IHC was diffuse rather than plaque-like.
 
*** After a natural route of exposure, 100% of WTD were susceptible to scrapie.
 
Deer developed clinical signs of wasting and mental depression and were necropsied from 28 to 33 months PI. Tissues from these deer were positive for PrPSc by IHC and WB. Similar to IC inoculated deer, samples from these deer exhibited two different molecular profiles: samples from obex resembled CWD whereas those from cerebrum were similar to the original scrapie inoculum. On further examination by WB using a panel of antibodies, the tissues from deer with scrapie exhibit properties differing from tissues either from sheep with scrapie or WTD with CWD. Samples from WTD with CWD or sheep with scrapie are strongly immunoreactive when probed with mAb P4, however, samples from WTD with scrapie are only weakly immunoreactive. In contrast, when probed with mAb’s 6H4 or SAF 84, samples from sheep with scrapie and WTD with CWD are weakly immunoreactive and samples from WTD with scrapie are strongly positive. This work demonstrates that WTD are highly susceptible to sheep scrapie, but on first passage, scrapie in WTD is differentiable from CWD.
 
 
2011
 
*** After a natural route of exposure, 100% of white-tailed deer were susceptible to scrapie.
 

TUESDAY, MARCH 28, 2017 

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



CWD TO CATTLE

***In contrast, cattle are highly susceptible to white-tailed deer CWD and mule deer CWD in experimental conditions but no natural CWD infections in cattle have been reported (Sigurdson, 2008; Hamir et al., 2006). It is not known how susceptible humans are to CWD but given that the prion can be present in muscle, it is likely that humans have been exposed to the agent via consumption of venison (Sigurdson, 2008). Initial experimental research, however, suggests that human susceptibility to CWD is low and there may be a robust species barrier for CWD transmission to humans (Sigurdson, 2008). It is apparent, though, that CWD is affecting wild and farmed cervid populations in endemic areas with some deer populations decreasing as a result.

SNIP...


price of prion poker goes up for cwd to cattle;

Monday, April 04, 2016

*** Limited amplification of chronic wasting disease prions in the peripheral tissues of intracerebrally inoculated cattle ***


*** PLEASE SEE THIS URGENT UPDATE ON CWD AND FEED ANIMAL PROTEIN ***

cwd to pig, orally ;

Research Project: TRANSMISSION, DIFFERENTIATION, AND PATHOBIOLOGY OF TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES

Location: Virus and Prion Research

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

Author item Moore, Sarah item Kunkle, Robert item Kondru, Naveen item Manne, Sireesha item Smith, Jodi item Kanthasamy, Anumantha item West Greenlee, M item Greenlee, Justin

Submitted to: Prion Publication Type: Abstract Only Publication Acceptance Date: 3/15/2017 Publication Date: N/A Citation: N/A Interpretive Summary:

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

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

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

This study demonstrates that PrPSc accumulates in lymphoid tissues from pigs challenged intracranially or orally with the CWD agent, and can be detected as early as 4 months after challenge.

CWD-infected pigs rarely develop clinical disease and if they do, they do so after a long incubation period. This raises the possibility that CWD-infected pigs could shed prions into their environment long before they develop clinical disease.

Furthermore, lymphoid tissues from CWD-infected pigs could present a potential source of CWD infectivity in the animal and human food chains.


CONFIDENTIAL

EXPERIMENTAL PORCINE SPONGIFORM ENCEPHALOPATHY

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


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


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


 snip...see much more here ;

WEDNESDAY, APRIL 05, 2017

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


MONDAY, AUGUST 14, 2017 

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



TUESDAY, APRIL 18, 2017 

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



OFFICIAL REPORT U.K. GOVERNMENT DEFRA

What is the risk of chronic wasting disease being introduced into Great Britain? A Qualitative Risk Assessment October 2012

Several different animal feed products are imported into GB from North America. These include processed pet foods and consignments of unfinished feed ingredients for use in animal feed. The amount of imported feed, including pet food, that contains cervid protein is unknown and identified as a significant data gap. As non-ruminant animal feed may be produced with cervid protein (but not from positive CWD animals) in the United States (US), there is a greater than negligible risk that feed with cervid protein is imported from North America into GB. There is, however, uncertainty associated with this estimate.

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...

What is the risk of chronic wasting disease being introduced into Great Britain? A Qualitative Risk Assessment October 2012


Thursday, April 07, 2016

What is the risk of chronic wasting disease being introduced into Great Britain? An updated Qualitative Risk Assessment March 2016



SATURDAY, NOVEMBER 4, 2017 

FDA 589.2000, Section 21 C.F.R. Animal Proteins Prohibited in Ruminant Feed WARNING Letters and FEED MILL VIOLATIONS OBSERVATIONS 2017 to 2006



FRIDAY, NOVEMBER 3, 2017

BSE MAD COW TSE PRION DISEASE PET FOOD FEED IN COMMERCE INDUSTRY VS TERRY S. SINGELTARY Sr. A REVIEW

''I have a neighbor who is a dairy farmer. He tells me that he knows of several farmers who feed their cattle expired dog food. These farmers are unaware of any dangers posed to their cattle from the pet food contents. For these farmers, the pet food is just another source of protein.''

IN CONFIDENCE


*USA USDA CWD BSE SCRAPIE TSE PRION?

3. Prof. A. Robertson gave a brief account of BSE. The US approach was to accord it a very low profile indeed. Dr. A Thiermann showed the picture in the ''Independent'' with cattle being incinerated and thought this was a fanatical incident to be avoided in the US at all costs. ...


Evidence That Transmissible Mink Encephalopathy Results from Feeding Infected Cattle Over the next 8-10 weeks, approximately 40% of all the adult mink on the farm died from TME. snip... The rancher was a ''dead stock'' feeder using mostly (>95%) downer or dead dairy cattle... 

In Confidence - Perceptions of unconventional slow virus diseases of animals in the USA - APRIL-MAY 1989 - G A H Wells 3. Prof. A. Robertson gave a brief account of BSE. The US approach was to accord it a very low profile indeed. Dr. A Thiermann showed the picture in the ''Independent'' with cattle being incinerated and thought this was a fanatical incident to be avoided in the US at all costs. ... 


The occurrence of CWD must be viewed against the contest of the locations in which it occurred. It was an incidental and unwelcome complication of the respective wildlife research programmes. Despite its subsequent recognition as a new disease of cervids, therefore justifying direct investigation, no specific research funding was forthcoming. The USDA veiwed it as a wildlife problem and consequently not their province! ...page 26.


KOREA BANS CANADIAN ELK IMPORTS: According to the Calgary Sun, Korea has moved to ban imports of Canadian deer and elk products (antlers and antler velvet) due to the outbreak of Chronic Wasting Disease (CWD) in Saskatchewan elk herds. Late last year, the Canadian Food Inspection Agency (CFIA) ordered the slaughter of 1,700 domesticated elk at six Saskatchewan farms in attempt to stop the spread of CWD (see CA 0206). The disease has not been detected in any other province. Canada's elk population is estimated at 53,000 head and is raised primarily for antler velvet. Canada is the fourth-largest antler velvet producer in the world, behind New Zealand, China and Russia. Most of Canadian antler velvet is exported to Asia where it is sold for medicinal purposes and as an aphrodisiac.


*** Spreading CWD around, or Trucking CWD or shipping CWD i.e. interstate, INTERNATIONAL movement of CWD by transportation of cervid or cervid materials

 Between 1996 and 2002, chronic wasting disease was diagnosed in 39 herds of farmed elk in Saskatchewan in a single epidemic. All of these herds were depopulated as part of the Canadian Food Inspection Agency’s (CFIA) disease eradication program. Animals, primarily over 12 mo of age, were tested for the presence CWD prions following euthanasia. Twenty-one of the herds were linked through movements of live animals with latent CWD from a single infected source herd in Saskatchewan, 17 through movements of animals from 7 of the secondarily infected herds.

 ***The source herd is believed to have become infected via importation of animals from a game farm in South Dakota where CWD was subsequently diagnosed (7,4). A wide range in herd prevalence of CWD at the time of herd depopulation of these herds was observed. Within-herd transmission was observed on some farms, while the disease remained confined to the introduced animals on other farms.


 Friday, May 13, 2011

 Chronic Wasting Disease (CWD) outbreaks and surveillance program in the Republic of Korea

 Hyun-Joo Sohn, Yoon-Hee Lee, Min-jeong Kim, Eun-Im Yun, Hyo-Jin Kim, Won-Yong Lee, Dong-Seob Tark, In- Soo Cho, Foreign Animal Disease Research Division, National Veterinary Research and Quarantine Service, Republic of Korea

 Chronic wasting disease (CWD) has been recognized as an important prion disease in native North America deer and Rocky mountain elks. The disease is a unique member of the transmissible spongiform encephalopathies (TSEs), which naturally affects only a few species. CWD had been limited to USA and Canada until 2000.

 On 28 December 2000, information from the Canadian government showed that a total of 95 elk had been exported from farms with CWD to Korea. These consisted of 23 elk in 1994 originating from the so-called “source farm” in Canada, and 72 elk in 1997, which had been held in pre export quarantine at the “source farm”.Based on export information of CWD suspected elk from Canada to Korea, CWD surveillance program was initiated by the Ministry of Agriculture and Forestry (MAF) in 2001.

 All elks imported in 1997 were traced back, however elks imported in 1994 were impossible to identify. CWD control measures included stamping out of all animals in the affected farm, and thorough cleaning and disinfection of the premises. In addition, nationwide clinical surveillance of Korean native cervids, and improved measures to ensure reporting of CWD suspect cases were implemented.

 Total of 9 elks were found to be affected. CWD was designated as a notifiable disease under the Act for Prevention of Livestock Epidemics in 2002.

 Additional CWD cases - 12 elks and 2 elks - were diagnosed in 2004 and 2005.

 Since February of 2005, when slaughtered elks were found to be positive, all slaughtered cervid for human consumption at abattoirs were designated as target of the CWD surveillance program. Currently, CWD laboratory testing is only conducted by National Reference Laboratory on CWD, which is the Foreign Animal Disease Division (FADD) of National Veterinary Research and Quarantine Service (NVRQS).

 In July 2010, one out of 3 elks from Farm 1 which were slaughtered for the human consumption was confirmed as positive. Consequently, all cervid – 54 elks, 41 Sika deer and 5 Albino deer – were culled and one elk was found to be positive. Epidemiological investigations were conducted by Veterinary Epidemiology Division (VED) of NVRQS in collaboration with provincial veterinary services.

 Epidemiologically related farms were found as 3 farms and all cervid at these farms were culled and subjected to CWD diagnosis. Three elks and 5 crossbreeds (Red deer and Sika deer) were confirmed as positive at farm 2.

 All cervids at Farm 3 and Farm 4 – 15 elks and 47 elks – were culled and confirmed as negative.

 Further epidemiological investigations showed that these CWD outbreaks were linked to the importation of elks from Canada in 1994 based on circumstantial evidences. 

In December 2010, one elk was confirmed as positive at Farm 5. Consequently, all cervid – 3 elks, 11 Manchurian Sika deer and 20 Sika deer – were culled and one Manchurian Sika deer and seven Sika deer were found to be positive. This is the first report of CWD in these sub-species of deer. Epidemiological investigations found that the owner of the Farm 2 in CWD outbreaks in July 2010 had co-owned the Farm 5.

 In addition, it was newly revealed that one positive elk was introduced from Farm 6 of Jinju-si Gyeongsang Namdo. All cervid – 19 elks, 15 crossbreed (species unknown) and 64 Sika deer – of Farm 6 were culled, but all confirmed as negative.






Subject: cwd genetic susceptibility 

Genetic susceptibility to chronic wasting disease in free-ranging white-tailed deer: Complement component C1q and Prnp polymorphisms§ 

Julie A. Blanchong a, *, Dennis M. Heisey b , Kim T. Scribner c , Scot V. Libants d , Chad Johnson e , Judd M. Aiken e , Julia A. Langenberg f , Michael D. Samuel g

snip...

Identifying the genetic basis for heterogeneity in disease susceptibility or progression can improve our understanding of individual variation in disease susceptibility in both free-ranging and captive populations. What this individual variation in disease susceptibility means for the trajectory of disease in a population, however, is not straightforward. For example, the greater, but not complete, resistance to CWD in deer with at least one Serine (S) at amino acid 96 of the Prnp gene appears to be associated with slower progression of disease (e.g., Johnson et al., 2006; Keane et al., 2008a). If slower disease progression results in longer-lived, infected deer with longer periods of infectiousness, resistance may lead to increased disease transmission rates, higher prion concentrations in the environment, and increased prevalence, as has been observed in some captive deer herds (Miller et al., 2006; Keane et al., 2008a). Alternatively, if the slower progression of disease in resistant deer is not associated with longer periods of infectiousness, but might instead indicate a higher dose of PrPCWD is required for infection, transmission rates in the population could decline especially if, as in Wisconsin, deer suffer high rates of mortality from other sources (e.g., hunting). Clearly, determining the relationship between genetic susceptibility to infection, dose requirements, disease progression, and the period of PrPCWD infectiousness are key components for understanding the consequences of CWD to free-ranging populations. 







Prion protein gene sequence and chronic wasting disease susceptibility in white-tailed deer (Odocoileus virginianus)

Adam L Brandt,1 Amy C Kelly,1 Michelle L Green,1,2 Paul Shelton,3 Jan Novakofski,2,* and Nohra E Mateus-Pinilla1,2 Author information ► Article notes ► Copyright and License information ► 

The sequence of the prion protein gene (PRNP) affects susceptibility to spongiform encephalopathies, or prion diseases in many species. In white-tailed deer, both coding and non-coding single nucleotide polymorphisms have been identified in this gene that correlate to chronic wasting disease (CWD) susceptibility. Previous studies examined individual nucleotide or amino acid mutations; here we examine all nucleotide polymorphisms and their combined effects on CWD. A 626 bp region of PRNP was examined from 703 free-ranging white-tailed deer. Deer were sampled between 2002 and 2010 by hunter harvest or government culling in Illinois and Wisconsin. Fourteen variable nucleotide positions were identified (4 new and 10 previously reported). We identified 68 diplotypes comprised of 24 predicted haplotypes, with the most common diplotype occurring in 123 individuals. Diplotypes that were found exclusively among positive or negative animals were rare, each occurring in less than 1% of the deer studied. Only one haplotype (C, odds ratio 0.240) and 2 diplotypes (AC and BC, odds ratios of 0.161 and 0.108 respectively) has significant associations with CWD resistance. Each contains mutations (one synonymous nucleotide 555C/T and one nonsynonymous nucleotide 286G/A) at positions reported to be significantly associated with reduced CWD susceptibility. Results suggest that deer populations with higher frequencies of haplotype C or diplotypes AC and BC might have a reduced risk for CWD infection – while populations with lower frequencies may have higher risk for infection. Understanding the genetic basis of CWD has improved our ability to assess herd susceptibility and direct management efforts within CWD infected areas.

KEYWORDS: CWD, diplotype, G96S, PRNP, prion, synonymous polymorphism, haplotype 

snip... 

A solid understanding of the genetics of CWD in white-tailed deer is vital to improve management of CWD on the landscape. Most TSEs are found in domestic or captive animals where management of infected individuals is feasible. For example, scrapie infected flocks can be handled through a process generally involving genetic testing, removal and destruction of infected or suspect animals, followed by decontamination of facilities and equipment.55Containment of free ranging deer in wild populations potentially infected with CWD and decontamination of the environment is not reasonably possible. The long term effects of CWD are not yet known but it is conceivable that an unmanaged infected population would be gradually extirpated as the disease progresses56,57 or at least reduced to low densities with high disease prevalence.58,59 Either outcome would have severe ecological effects (e.g., deer play a major role in affecting plant communities60 and as a prey source61,62) as well as negative economic impacts to hunting. Overall disease prevalence has remained at relatively low levels in Illinois compared to Wisconsin.11 It is important to note that at the time of sampling, CWD had been found in 6 Illinois counties and has since been detected in 14.9Complete eradication of CWD among free ranging white-tailed deer may not be possible; however, an active containment effort in Illinois appears to have prevented significant increases in prevalence.9,11,12 Further examination of PRNP haplotype and diplotype frequencies across northern Illinois and southern Wisconsin in conjunction with population structure and movement45,63,64 will be useful in identifying localities with greater or reduced susceptibility risk. Effectiveness of CWD containment efforts can be aided through genetic testing and redirecting management resources.


***at present, no cervid PrP allele conferring absolute resistance to prion infection has been identified. 

P-145 Estimating chronic wasting disease resistance in cervids using real time quaking- induced conversion 

Nicholas J Haley1, Rachel Rielinqer2, Kristen A Davenport3, W. David Walter4, Katherine I O'Rourke5, Gordon Mitchell6, Juergen A Richt2 1 Department of Microbiology and Immunology, Midwestern University, United States; 2Department of Diagnostic Medicine and Pathobiology, Kansas State University; 3Prion Research Center; Colorado State University; 4U.S. Geological Survey, Pennsylvania Cooperative Fish and Wildlife Research Unit; 5Agricultural Research Service, United States Department of Agriculture; 6Canadian Food Inspection Agency, National and OlE Reference Laboratory for Scrapie and CWD 

In mammalian species, the susceptibility to prion diseases is affected, in part, by the sequence of the host's prion protein (PrP). In sheep, a gradation from scrapie susceptible to resistant has been established both in vivo and in vitro based on the amino acids present at PrP positions 136, 154, and 171, which has led to global breeding programs to reduce the prevalence of scrapie in domestic sheep. In cervids, resistance is commonly characterized as a delayed progression of chronic wasting disease (CWD); at present, no cervid PrP allele conferring absolute resistance to prion infection has been identified. To model the susceptibility of various naturally-occurring and hypothetical cervid PrP alleles in vitro, we compared the amplification rates and efficiency of various CWD isolates in recombinant PrPC using real time quaking-induced conversion. We hypothesized that amplification metrics of these isolates in cervid PrP substrates would correlate to in vivo susceptibility - allowing susceptibility prediction for alleles found at 10 frequency in nature, and that there would be an additive effect of multiple resistant codons in hypothetical alleles. Our studies demonstrate that in vitro amplification metrics predict in vivo susceptibility, and that alleles with multiple codons, each influencing resistance independently, do not necessarily contribute additively to resistance. Importantly, we found that the white-tailed deer 226K substrate exhibited the slowest amplification rate among those evaluated, suggesting that further investigation of this allele and its resistance in vivo are warranted to determine if absolute resistance to CWD is possible. 

***at present, no cervid PrP allele conferring absolute resistance to prion infection has been identified. 

PRION 2016 CONFERENCE TOKYO 


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

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



MONDAY, SEPTEMBER 25, 2017

Colorado Chronic Wasting Disease CWD TSE Prion Mandatory Submission of test samples in some areas and zoonosis

(ALSO, see the debate and evidence showing the origin of CWD starting in Colorado captive research pen)


the tse prion aka mad cow type disease is not your normal pathogen. 

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

you cannot cook the TSE prion disease out of meat. 

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

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

the TSE prion agent also survives Simulated Wastewater Treatment Processes. 

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

you can bury it and it will not go away. 

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

it’s not your ordinary pathogen you can just cook it out and be done with. 

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

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

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

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

Laboratory of Central Nervous System Studies, National Institute of 

Neurological Disorders and Stroke, National Institutes of Health, 

Bethesda, MD 20892. 

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

PMID: 8006664 [PubMed - indexed for MEDLINE] 


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 



URINE

SUNDAY, JULY 16, 2017

*** Temporal patterns of chronic wasting disease prion excretion in three cervid species ***


FRIDAY, NOVEMBER 24, 2017 

Norwegian Food Safety Authority makes changes to measures to limit the spread of disease Skrantesjuke (CWD) in deer wildlife


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

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


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. 
 
***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. 
 
 
 
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 *** 
 
 
*** Infectious agent of sheep scrapie may persist in the environment for at least 16 years *** 
 
Gudmundur Georgsson1, Sigurdur Sigurdarson2 and Paul Brown3 
 
 
with CWD TSE Prions, I am not sure there is any absolute yet, other than what we know with transmission studies, and we know tse prion kill, and tse prion are bad. science shows to date, that indeed soil, dirt, some better than others, can act as a carrier. same with objects, farm furniture. take it with how ever many grains of salt you wish, or not. if load factor plays a role in the end formula, then everything should be on the table, in my opinion...tss
 
 
 Oral Transmissibility of Prion Disease Is Enhanced by Binding to Soil Particles
 
Author Summary
 
Transmissible spongiform encephalopathies (TSEs) are a group of incurable neurological diseases likely caused by a misfolded form of the prion protein. TSEs include scrapie in sheep, bovine spongiform encephalopathy (‘‘mad cow’’ disease) in cattle, chronic wasting disease in deer and elk, and Creutzfeldt-Jakob disease in humans. Scrapie and chronic wasting disease are unique among TSEs because they can be transmitted between animals, and the disease agents appear to persist in environments previously inhabited by infected animals. Soil has been hypothesized to act as a reservoir of infectivity and to bind the infectious agent. In the current study, we orally dosed experimental animals with a common clay mineral, montmorillonite, or whole soils laden with infectious prions, and compared the transmissibility to unbound agent. We found that prions bound to montmorillonite and whole soils remained orally infectious, and, in most cases, increased the oral transmission of disease compared to the unbound agent. The results presented in this study suggest that soil may contribute to environmental spread of TSEs by increasing the transmissibility of small amounts of infectious agent in the environment.
 
 
tse prion soil
 
 
 
 
 
Wednesday, December 16, 2015
 
Objects in contact with classical scrapie sheep act as a reservoir for scrapie transmission
 
 
The sources of dust borne prions are unknown but it seems reasonable to assume that faecal, urine, skin, parturient material and saliva-derived prions may contribute to this mobile environmental reservoir of infectivity. This work highlights a possible transmission route for scrapie within the farm environment, and this is likely to be paralleled in CWD which shows strong similarities with scrapie in terms of prion dissemination and disease transmission. The data indicate that the presence of scrapie prions in dust is likely to make the control of these diseases a considerable challenge.
 
 
>>>Particle-associated PrPTSE molecules may migrate from locations of deposition via transport processes affecting soil particles, including entrainment in and movement with air and overland flow. <<<
 
Fate of Prions in Soil: A Review
 
Christen B. Smith, Clarissa J. Booth, and Joel A. Pedersen*
 
Several reports have shown that prions can persist in soil for several years. Significant interest remains in developing methods that could be applied to degrade PrPTSE in naturally contaminated soils. Preliminary research suggests that serine proteases and the microbial consortia in stimulated soils and compost may partially degrade PrPTSE. Transition metal oxides in soil (viz. manganese oxide) may also mediate prion inactivation. Overall, the effect of prion attachment to soil particles on its persistence in the environment is not well understood, and additional study is needed to determine its implications on the environmental transmission of scrapie and CWD.
 
 
P.161: Prion soil binding may explain efficient horizontal CWD transmission
 
Conclusion. Silty clay loam exhibits highly efficient prion binding, inferring a durable environmental reservoir, and an efficient mechanism for indirect horizontal CWD transmission.
 
 
>>>Another alternative would be an absolute prohibition on the movement of deer within the state for any purpose. While this alternative would significantly reduce the potential spread of CWD, it would also have the simultaneous effect of preventing landowners and land managers from implementing popular management strategies involving the movement of deer, and would deprive deer breeders of the ability to engage in the business of buying and selling breeder deer. Therefore, this alternative was rejected because the department determined that it placed an avoidable burden on the regulated community.<<<
 
Wednesday, December 16, 2015
 
Objects in contact with classical scrapie sheep act as a reservoir for scrapie transmission
 
Timm Konold1*, Stephen A. C. Hawkins2, Lisa C. Thurston3, Ben C. Maddison4, Kevin C. Gough5, Anthony Duarte1 and Hugh A. Simmons1
 
1 Animal Sciences Unit, Animal and Plant Health Agency Weybridge, Addlestone, UK, 2 Pathology Department, Animal and Plant Health Agency Weybridge, Addlestone, UK, 3 Surveillance and Laboratory Services, Animal and Plant Health Agency Penrith, Penrith, UK, 4 ADAS UK, School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington, UK, 5 School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington, UK
 
Classical scrapie is an environmentally transmissible prion disease of sheep and goats. Prions can persist and remain potentially infectious in the environment for many years and thus pose a risk of infecting animals after re-stocking. In vitro studies using serial protein misfolding cyclic amplification (sPMCA) have suggested that objects on a scrapie affected sheep farm could contribute to disease transmission. This in vivo study aimed to determine the role of field furniture (water troughs, feeding troughs, fencing, and other objects that sheep may rub against) used by a scrapie-infected sheep flock as a vector for disease transmission to scrapie-free lambs with the prion protein genotype VRQ/VRQ, which is associated with high susceptibility to classical scrapie. When the field furniture was placed in clean accommodation, sheep became infected when exposed to either a water trough (four out of five) or to objects used for rubbing (four out of seven). This field furniture had been used by the scrapie-infected flock 8 weeks earlier and had previously been shown to harbor scrapie prions by sPMCA. Sheep also became infected (20 out of 23) through exposure to contaminated field furniture placed within pasture not used by scrapie-infected sheep for 40 months, even though swabs from this furniture tested negative by PMCA. This infection rate decreased (1 out of 12) on the same paddock after replacement with clean field furniture. Twelve grazing sheep exposed to field furniture not in contact with scrapie-infected sheep for 18 months remained scrapie free. The findings of this study highlight the role of field furniture used by scrapie-infected sheep to act as a reservoir for disease re-introduction although infectivity declines considerably if the field furniture has not been in contact with scrapie-infected sheep for several months. PMCA may not be as sensitive as VRQ/VRQ sheep to test for environmental contamination.
 
snip...
 
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 ***
 
 
*** Infectious agent of sheep scrapie may persist in the environment for at least 16 years ***
 
Gudmundur Georgsson1, Sigurdur Sigurdarson2 and Paul Brown3
 
 
MONDAY, JUNE 12, 2017
 
Rethinking Major grain organizations opposition to CFIA's control zone approach to Chronic Wasting CWD TSE Prion Mad Deer Type Disease 2017?
 
 WEDNESDAY, MAY 17, 2017
 
*** Chronic Wasting Disease CWD TSE Prion aka Mad Deer Disease and the Real Estate Market Land Values ***
 

TUESDAY, NOVEMBER 7, 2017 

OIE Opens Texas Office Bovine Spongiform Encephalopathy BSE, Scrapie, CWD, TSE Prion


THURSDAY, NOVEMBER 30, 2017 

Norway Animal welfare surveillance at Nordfjella Skrantesjuke CWD TSE Prion Update


WEDNESDAY, NOVEMBER 29, 2017

 Norway another case of Skrantesjuke CWD TSE Prion Adult Reindeer pitcher field in Nordfjella (preliminary testing) 13th case if confirmed


FRIDAY, NOVEMBER 24, 2017 

Norwegian Food Safety Authority makes changes to measures to limit the spread of disease Skrantesjuke (CWD) in deer wildlife


SATURDAY, NOVEMBER 18, 2017 

Norway detects more Chronic Wasting Disease CWD TSE Prion Skrantesjuke

This is the eighth case of the lethal deer disease in the area since the survey started in 2016.

The reindeer cub was shot by a flock from the Norwegian National Guard, and the infectious agent was detected in the animal's lymph nodes.


WEDNESDAY, NOVEMBER 01, 2017 

Norway detects CWD Skrantesjuke Deer possibly atypical Nor-98-type TSE?

Greetings TSE prion world, 

i am seeing more and more references to the atypical Nor-98-type CWD TSE Prion in Norway as being of the non-infectious or non-infective variant. with science documented to date, i do not believe that any CWD Skrantesjuke TSE Prion typical or atypical in Norway or anywhere else can be classified as ''non-infective variant''. IF, Norway takes the USDA OIE views and makes atypical Nor-98 type CWD in Deer a International trading commodity fueled by junk science, as they did with sheep, i.e. no trade restrictions for Nor-98 in sheep, the world should then weep...terry 

Nor-98 atypical Scrapie Transmission Studies Review

snip...see full text;



FRIDAY, OCTOBER 13, 2017 

Norway, Two More New Cases of Chronic Wasting Disease CWD TSE Prion Skrantesjuke


TUESDAY, OCTOBER 10, 2017

Norway detects another case of CWD TSE PRION Skrantesjuke


SATURDAY, SEPTEMBER 30, 2017 

Norway, CWD TSE Prion, Humans, Zoonosis, Fortsatt lite sannsynlig at mennesker kan smittes av skrantesyke?


MONDAY, AUGUST 14, 2017 

NORWAY CWD, SHEEP GRAZING, and Scrapie, What If?


TUESDAY, JUNE 20, 2017 

Norway Confirms 6th Case of Skrantesjuke CWD TSE Prion Disease


Tuesday, December 13, 2016

Norway Chronic Wasting Disease CWD TSE Prion disease Skrantesjuke December 2016 Update


Thursday, September 22, 2016

NORWAY DETECTS 5TH CASE OF CHRONIC WASTING DISEASE CWD TSE PRION Skrantesjuke


Saturday, September 03, 2016

NORWAY Regulation concerning temporary measures to reduce the spread of Chronic Wasting Disease (CWD) as 4th case of skrantesjuke confirmed in Sogn og Fjordane


Wednesday, August 31, 2016

*** NORWAY CONFIRMS 4TH CASE OF CHRONIC WASTING DISEASE CWD TSE PRION IN SECOND CARIBOU


Wednesday, August 31, 2016

NORWAY CONFIRMS 4TH CASE OF CHRONIC WASTING DISEASE CWD TSE PRION IN SECOND CARIBOU


Tuesday, August 02, 2016

Chronic wasting disease of deer – is the battle to keep Europe free already lost?


Tuesday, June 14, 2016

*** Chronic Wasting Disease (CWD) in a moose from Selbu in Sør-Trøndelag Norway ***


Thursday, July 07, 2016

Norway reports a third case Chronic Wasting Disease CWD TSE Prion in 2nd Norwegian moose

14/06/2016 - Norway reports a third case


Tuesday, April 12, 2016

The first detection of Chronic Wasting Disease (CWD) in Europe free-ranging reindeer from the Nordfjella population in South-Norway.


Saturday, April 9, 2016

The Norwegian Veterinary Institute (NVI, 2016) has reported a case of prion disease Cervid Spongiform Encephalopathy detected in free ranging wild reindeer (Rangifer tarandus tarandus)

Department for Environment, Food and Rural Affairs


Saturday, July 16, 2016

Chronic wasting Disease in Deer (CWD or Spongiform Encephalopathy) The British Deer Society 07/04/2016

Red Deer Ataxia or Chronic Wasting Disease CWD TSE PRION?

could this have been cwd in the UK back in 1970’S ??? 




Clinical Communication Enzootic ataxia in Red deer 

P.R. Wilson , Marjorie B. Orr & E.L. Key Pages 252-254 | Published online: 23 Feb 2011


SEE FULL TEXT ;




***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.***



Volume 2: Science 

4. The link between BSE and vCJD 

Summary 

4.29 The evidence discussed above that vCJD is caused by BSE seems overwhelming. Uncertainties exist about the cause of CJD in farmers, their wives and in several abattoir workers. It seems that farmers at least might be at higher risk than others in the general population. 1 Increased ascertainment (ie, increased identification of cases as a result of greater awareness of the condition) seems unlikely, as other groups exposed to risk, such as butchers and veterinarians, do not appear to have been affected. The CJD in farmers seems to be similar to other sporadic CJD in age of onset, in respect to glycosylation patterns, and in strain-typing in experimental mice. Some farmers are heterozygous for the methionine/valine variant at codon 129, and their lymphoreticular system (LRS) does not contain the high levels of PrPSc found in vCJD. It remains a remote possibility that when older people contract CJD from BSE the resulting phenotype is like sporadic CJD and is distinct from the vCJD phenotype in younger people.

4.30 Estimates of the likely scale of a possible epidemic of vCJD are wide-ranging and the subject of much debate. To know the likely number of cases is very important, not least to enable preparations to be made for the care of victims, as well as to be able to draw up guidelines to reduce the risk of transmission from infected but asymptomatic people. Preliminary results of the study examining tonsil and appendix material for signs of infection were not informative in this regard and full results are awaited. A blood test that would allow the widespread screening of the population by a simple method is still being sought.


>>> MONDAY, NOVEMBER 06, 2017 <<<

*** Experimental transfusion of variant CJD-infected blood reveals previously uncharacterised prion disorder in mice and macaque ***

''On secondary and tertiary transmissions, however, the proportion of PrPres positive animals gradually increased to almost 100%. Recent communications suggest that a similar situation might exist in other models of experimental exposure to prions involving swine32 and cattle33. '' 

''Experimental transfusion of variant CJD-infected blood reveals previously uncharacterised prion disorder in mice and macaque''

In conclusion, the range of incomplete syndromes that we observed between healthy carriers and typical vCJD indicates that multiple forms of prion variants can coexist and may emerge in different forms depending upon the conditions under which transmission occurred. This has obvious consequences for public health, and questions the uniqueness of the BSE/vCJD strain50 and our capacity to detect and prevent all infectious forms of prion disease. 



SATURDAY, DECEMBER 02, 2017 

Public health risks from subclinical variant CJD



2001 FDA CJD TSE Prion Singeltary Submission

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


MONDAY, OCTOBER 02, 2017 

Creutzfeldt Jakob Disease United States of America USA and United Kingdom UK Increasing and Zoonotic Pontential From Different Species



THURSDAY, AUGUST 17, 2017 

*** Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob disease in the United States revisited 2017 Singeltary et al



WEDNESDAY, NOVEMBER 1, 2017 

Blood-derived amyloid-β protein induces Alzheimer’s disease pathologies



SPONTANEOUS ATYPICAL BOVINE SPONGIFORM ENCEPHALOPATHY

***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.***



Diagnosis and Reporting of Creutzfeldt-Jakob Disease 

Singeltary, Sr et al. JAMA.2001; 285: 733-734. Vol. 285 No. 6, February 14, 2001 JAMA Diagnosis and Reporting of Creutzfeldt-Jakob Disease 

To the Editor: 

In their Research Letter, Dr Gibbons and colleagues1 reported that the annual US death rate due to Creutzfeldt-Jakob disease (CJD) has been stable since 1985. These estimates, however, are based only on reported cases, and do not include misdiagnosed or preclinical cases. It seems to me that misdiagnosis alone would drastically change these figures. An unknown number of persons with a diagnosis of Alzheimer disease in fact may have CJD, although only a small number of these patients receive the postmortem examination necessary to make this diagnosis. Furthermore, only a few states have made CJD reportable. Human and animal transmissible spongiform encephalopathies should be reportable nationwide and internationally. 

Terry S. Singeltary, Sr Bacliff, Tex 

1. Gibbons RV, Holman RC, Belay ED, Schonberger LB. Creutzfeldt-Jakob disease in the United States: 1979-1998. JAMA. 2000;284:2322-2323. 




just made a promise to mom (dod 12/14/97 confirmed hvCJD), never forget, and never let them forget...


Oh, what a tangled web we weave when first we practice to deceive!


Terry S. Singeltary Sr.

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