Wednesday, December 23, 2020

Idiopathic Brainstem Neuronal Chromatolysis IBNC BSE TSE Prion a Review 2020

Idiopathic Brainstem Neuronal Chromatolysis IBNC BSE TSE Prion a Review 2020

Published: 30 September 2008

Idiopathic Brainstem Neuronal Chromatolysis (IBNC): a novel prion protein related disorder of cattle?

Martin Jeffrey, Belinda Baquero Perez, Stuart Martin, Linda Terry & Lorenzo González BMC Veterinary Research volume 4, Article number: 38 (2008) Cite this article

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Abstract

Background

The epidemic form of Bovine Spongiform Encephalopathy (BSE) is generally considered to have been caused by a single prion strain but at least two strain variants of cattle prion disorders have recently been recognized. An additional neurodegenerative condition, idiopathic brainstem neuronal chromatolysis and hippocampal sclerosis (IBNC), a rare neurological disease of adult cattle, was also recognised in a sub-set of cattle submitted under the BSE Orders in which lesions of BSE were absent. Between the years of 1988 and 1991 IBNC occurred in Scotland with an incidence of 7 cases per 100,000 beef suckler cows over the age of 6 years.

Results

When the brains of 15 IBNC cases were each tested by immunohistochemistry, all showed abnormal labelling for prion protein (PrP). Immunohistological labelling for PrP was also present in the retina of a single case available for examination. The pattern of PrP labelling in brain is distinct from that seen in other ruminant prion diseases and is absent from brains with other inflammatory conditions and from normal control brains. Brains of IBNC cattle do not reveal abnormal PrP isoforms when tested by the commercial BioRad or Idexx test kits and do not reveal PrPres when tested by Western blotting using stringent proteinase digestion methods. However, some weakly protease resistant isoforms of PrP may be detected when tissues are examined using mild proteinase digestion techniques.

Discussion This study shows that the novel condition of cattle previously identified as IBNC and recognized from within the BSE suspect submissions, abnormally expresses or accumulates PrP in brain and retina. However, this abnormal PrP is not composed of isoforms that are strongly resistant to protease digestion suggesting that it is not present in the form of large aggregates.

Immunohistochemical demonstration of PrP labelling and increased levels of PrP mRNA have previously been described in adult humans affected with acute vascular disorders, in infants with perinatal hypoxia and experimental infarction of rodents [9]. These findings are considered to represent upregulation of PrP expression which encompasses part of the oxidative stress response of neurons. We have also observed increased PrP in the cytoplasm of neurons undergoing ischaemic degeneration in a variety of sheep encephalopathies. Though ischaemic neuronal degeneration is not a feature of IBNC, nevertheless, the presence of PrP within the cytoplasm of some chromatolytic and degenerate neurons of IBNC affected cattle is consistent with the idea that stressed neurons may respond by increasing PrP expression.

Though present in only two cows, the pattern of PrP accumulation within the granule cell layer of the cerebellum is morphologically similar to that reported by several authors for Nor 98 types of the transmissible spongiform encephalopathy or prion disease of sheep [3, 10]. The PrP accumulation within the plexiform layers of the eye is similar to that of both natural scrapie [11] and of Nor 98 (MJ personal observations). However the majority type of PrP labelling that occurred in all IBNC cases was found within the neuropil, mainly in the rostral neuraxis and cerebrum, the nature of which is previously unreported in cattle or in any other prion disorder. This novel pattern of labelling appears to correspond to a rarefaction or fine microvacuolation of neuropil as seen on standard HE stained sections.

Pathological, biochemical and bioassay data all suggest that the epidemic form of cattle BSE is a single strain. However, recent large scale EU wide surveillance for BSE has led to the unexpected discovery of rare and hitherto unknown prion diseases of cattle. Small numbers of atypical forms of cattle prion diseases have now been recognized from several European countries, in the USA and Japan and can be distinguished by histological, molecular and transmission characteristics [12–14]. Bovine Amyloidotic Spongiform Encephalopathy (BASE) was the first of these novel cattle prion disorders to be recognized and was characterized by the presence of numerous small amyloid deposits of abnormal PrP. It was initially discovered in three aged Italian cattle [1] and has subsequently been transmitted to transgenic mice [13, 14]. A further variant of a cattle prion disease affecting cows between 8 and 15 years was initially recognized in France [2] and has also been transmitted to mice. BSE and these novel cattle prion diseases can be distinguished using biochemical and molecular methods and are now classified as C, H and L type isolates [12]. H type and L type (BASE) isolates are defined according to the higher and lower positions of the unglycosylated PrPres bands in Western blots, respectively, when compared to the position of the corresponding band in classical BSE (C type) isolates [12]. L type cases formerly classified as BASE, have a distinctive glycopattern in which monoglycoslyated PrPres predominates compared to BSE [12, 14]. While IBNC cases are on average older than BSE cases they occupy a similar age class of cattle to that of H and L type cattle prion diseases, but IBNC can be readily distinguished from H, L and C type cattle prion disease by morphologic pathology and by the absence of PrPres under stringent conditions of protease digestion.

Not all abnormal PrPres isoforms detected from brains of animals affected with prion disease are resistant to stringent protease digestion. The PrPres of two sheep of the ARR/ARR PrP genotype affected with a classical scrapie-like disease accumulated unusually protease sensitive isoforms of PrP [15]. Similarly, the transmissible prion disease of sheep known as Nor 98 and related conditions (often referred to as atypical scrapie) also have weakly protease resistant PrPres [3, 16]. Nor 98 does not appear to transmit readily to other sheep under field conditions: it also does not transmit to conventional mice although it does readily transmit disease to one strain of transgenic mouse which substantially over-expresses the VRQ allele of sheep PrP [16, 17]. The transgenic PG14 mouse also has PrPres which is even more readily digested than that found in Nor 98 but this prion protein disorder has not so far been successfully transmitted [18]. The biochemical analyses of limited numbers of IBNC cases clearly shows that highly aggregated forms of protease resistant PrP are not present in brain tissue. However, when the data from the ELISA and immunoblot tests using mild protease digestion are compared with that of normal control material it is possible that smaller aggregates of PrP molecules may be present.

Conclusion

The study shows that a distinctive neurological disorder of cattle, which has some clinical similarities to BSE, is associated with abnormal PrP labelling in brain but the pathology and biochemistry of IBNC are distinct from BSE. The study is important either because it raises the possibility of a significant increase in the scope of prion disease or because it demonstrates that widespread and consistent PrP alterations may not be confined to prion diseases. Further studies, including transmission experiments, are needed to establish whether IBNC is a condition in which prion protein is abnormally regulated or it is yet a further example of an infectious cattle prion disease.

Conclusion

The present results indicate that there are changes in PrP expression or accumulation in the neurodegenerative cattle disorder known as IBNC. The pathology and biochemistry of IBNC are quite distinct from that of other prion diseases of cattle and other species but the pathology does include grey matter spongiform changes. The transmissibility of this disorder is undetermined. These results are interesting as they show that either the range of prion diseases and associated pathology is still wider than previously thought or that substantial abnormalities of prion protein expression may be associated with brain lesions unconnected with classical prion diseases. Further biochemical and transmission studies are needed to determine which of these possibilities is correct.


P.9.21 Molecular characterization of BSE in Canada

Jianmin Yang1, Sandor Dudas2, Catherine Graham2, Markus Czub3, Tim McAllister1, Stefanie Czub1 1Agriculture and Agri-Food Canada Research Centre, Canada; 2National and OIE BSE Reference Laboratory, Canada; 3University 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.

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

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




PLOS ONE Journal 

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


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

Terry S. Singeltary Sr., 03 Jul 2015 at 16:53 GMT

***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 ***

Greetings Plos et al,

in reference to;

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

I kindly wish to comment please, as follows.

I was stunned by this report.

This Research Report should have been titled ;

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

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

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

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

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

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

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

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

Too many _appears_ , appears this, appears that.

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

is this what science has come to?

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

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

it can be argued that there is potential for Alzheimer’s to be a low dose TSE Prion disease ;

http://www.plosone.org/an...

what about horizontal and or vertical transmission of an atypical strain of the BSE TSE prion disease into a low dose that is not detectible with TSE Prion testing to date?

what about a completely different strain, another atypical, of the TSE prion disease, to low to detect to date, and I stress to date?

to abandon the TSE prion and IBNC link there from would be foolish in my opinion.

SEAC, FatPride, BSE Inquiry, have never found a link to pesticides, or OP’s, or metals, as a _cause_, to any TSE prion disease.

I have also followed the metals, pesticide debate as a cause for the TSE prion disease. to date, this has proven to be fruitless for any _cause_ of the TSE prion disease. not to say the potential for these factors for one to be more susceptible to a TSE prion from surrounding environmental factors i.e. surrounding TSE prion exposures from the various routes and sources of the TSE prion disease (see metals and pesticide i.e. FatePride towards the bottom). from Mark Purdey and his research, to a farmer with BSE that treated his kids with OP’s for head lice, and nothing scientific to date has confirmed a link to the TSE prion disease as a _cause_.

We MUST not abandon transmission studies, and or any link to the TSE prion disease.

IT appears, in the absence of any scientific link to any specific herbicides, insecticides, parasiticides and other chemicals to date to IBNC, to just explore other options instead of the transmission studies to prove one way or the other whether or not the IBNC or BBD or whatever you want to call this, while ignoring the existing epidemiology and knowledge of the TSE prion disease with the primitive TSE prion testing to date, it appears all this would be foolish, it appears this would be very questionable, in my opinion. ...

Terry S. Singeltary Sr.

REFERENCES

1992 NEW BRAIN DISORDER 3. WHAT ABOUT REPORTS OF NEW FORM OF BSE ? http://collections.europa...

THE LINE TO TAKE ON IBNC $$$ 1995 $$$ 1995 page 9 of 14 ; *** 31. Mr. Bradley informed the Committee that the CVO had informed the CMO about the IBNC results and the transmission from retina and he, like the Committee was satisfied that the controls already in place or proposed were adequate. ... http://web.archive.org/we...

IN CONFIDENCE *** BSE ATYPICAL LESION DISTRIBUTION http://web.archive.org/we...

BSE: BRAIN STEM NEURONAL CHROMATOLYSIS – ‘’BOVINE BRAIN DISORDER’’ http://collections.europa...

zinc link to cows speculative http://collections.europa...

DRAFT IN CONFIDENCE IDIOPATHIC BRAIN STEM NEURONAL CHROMATOLYSIS AND HIPPOCAMPAL SCLEROSIS (Vet. Rec. 1992, M Jeffrey, J W Wilemsith p359-362 http://collections.europa...

BSE: DISCLOSURE OF INFORMATION AND FORECAST http://collections.europa...

SEAC idiopathic brainstem neuronal chromatolysis IBNC 2009 http://webarchive.nationa... http://webarchive.nationa...

NEW RESULTS ON IDIOPATHIC BRAINSTEM NEURONAL CHROMATOLYSIS "All of the 15 cattle tested showed that the brains had abnormally accumulated PrP" http://webarchive.nationa...

Atypical prion proteins and IBNC in cattle DEFRA project code SE1796 FOIA Final report These findings together might suggest an additional family of neurodegenerative diseases where the infectious form of PrP is not readily detected by our current diagnostic tests. IBNC is likely to represent a subset of this group of cattle. Based on these data, our overall conclusion is that a second type of BSE is unlikely to have co-existed at a high prevalence with the classical form in the cattle population during the UK epidemic. http://randd.defra.gov.uk...

Project Documents • Final Report - Annex : Atypical prion proteins in cattle (10064k) • Final Report - SID5 : Atypical prion proteins in cattle (201k) http://randd.defra.gov.uk... if links above do not work, see ; http://bse-atypical.blogs...

ITEM 6 FATEPRIDE (SEAC 97/4) 35. ***However, there was no evidence that environmental factors, including manganese, cause disease. http://www.seac.gov.uk/pa... http://webarchive.nationa...

FATEPriDE KEY FINDINGS ORGANOPHOSPHATE NO RELATIONSHIP TO CAUSE TSE http://webarchive.nationa...

OP'S MEETING WITH PURDEY http://web.archive.org/we...

Copper deficiency in the young bovine results in dramatic decreases in brain copper concentration ***but does not alter brain prion protein biology L. R. Legleiter, J. W. Spears and H. C. Liu Department of Animal Science and Interdepartmental Nutrition Program, North Carolina State University, Raleigh, NC http://www.ncbi.nlm.nih.g...

SEAC 103/1 SPONGIFORM ENCEPHALOPATHY ADVISORY COMMITTEE Draft minutes of the 102nd meeting held on 4th March 2009 Nobel House, 17 Smith Square, London SW1P 3JR

http://webarchive.nationa...

http://webarchive.nationa...

From: Terry S. Singeltary Sr.

Sent: Tuesday, August 13, 2013 3:58 PM

To: Science.Advisory.Council@defra.gsi.gov.uk

Subject: Idiopathic Brainstem Neuronal Chromatolysis (IBNC): a novel prion protein related disorder of cattle?

Greetings Honorable Science Advisory Council et al @ DEFRA,

I wish to ask a question about something I have seen no updates on, that concerns me.

IDIOPATHIC BRAINSTEM NEURONAL CHROMATOLYSIS IBNC or what I some times call, IBNC BSE.

I have seen nothing in the scientific literature updated on this in years, since around 2008, then it was like it fell off the face of the earth ?

can you please give me some sort of update on the IBNC BSE science to date ?

how many cases of IBNC BSE have been detected ?

is there an ongoing surveillance for this the IBNC BSE, and are the BSE test even capable of detecting it ?

could the USA and or North America even detect, if they were even looking for it ?

latest studies, if any more since "All of the 15 cattle tested showed that the brains had abnormally accumulated PrP" ?

thank you,

kind regards, terry

Research article Idiopathic Brainstem Neuronal Chromatolysis (IBNC): a novel prion protein related disorder of cattle? Martin Jeffrey1*, Belinda Baquero Perez2, Stuart Martin1, Linda Terry2 and Lorenzo González1

http://www.biomedcentral....

2015

PRION 2015 ORAL AND POSTER CONGRESSIONAL ABSTRACTS

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

***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.

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

O.08: H-type bovine spongiform encephalopathy associated with E211K prion protein polymorphism: Clinical and pathologic features in wild-type and E211K cattle following intracranial inoculation

S Jo Moore, M Heather West Greenlee, Jodi Smith, Eric Nicholson, Cathy Vrentas, and Justin Greenlee United States Department of Agriculture; Ames, IA USA

***This study demonstrates that the phenotype of E211K H-type BSE remains stable when transmitted to cattle without the E211K polymorphism, and exhibits a number of features that differ from classical BSE in both wild-type and E211K cattle.

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

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

***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.

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

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

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.136: Mother to offspring transmission of CWD—Detection in fawn tissues using the QuIC assay

Amy Nalls, Erin McNulty, Clare Hoover, Jeanette Hayes-Klug, Kelly Anderson, Edward Hoover, and Candace Mathiason Colorado State University; Fort Collins, CO USA

***Our findings demonstrate that transmission of prions from mother to offspring can occur, and *** may be underestimated for all prion diseases.

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

https://prion2015.files.w...

ALSO, PLEASE SEE ;

31 Jan 2015 at 20:14 GMT

*** Ruminant feed ban for cervids in the United States? ***

31 Jan 2015 at 20:14 GMT

http://www.plosone.org/an...

Saturday, May 30, 2015 PRION 2015 ORAL AND POSTER CONGRESSIONAL ABSTRACTS https://prion2015.files.w...

Wednesday, June 10, 2015 Zoonotic Potential of CWD Prions LATE-BREAKING ABSTRACTS https://prion2015.files.w... https://prion2015.files.w...

No documents available. Attachments View All (1) Docket No. APHIS-2014-0107 Bovine Spongiform Encephalopathy; Importation of Animals and Animal Products Singeltary Submission View Attachment: http://www.regulations.go...

Prion-like transmission and spreading of tau pathology Florence Clavaguera1, Jürgen Hench1, Michel Goedert2 and Markus Tolnay1,* DOI: 10.1111/nan.12197 http://onlinelibrary.wile...

Saturday, October 19, 2013 A comparative study of modified confirmatory techniques and additional immuno-based methods for non-conclusive autolytic Bovine spongiform encephalopathy cases http://www.biomedcentral....

spontaneous atypical BSE ??? As of December 2011, around 60 atypical BSE cases have currently been reported in 13 countries, *** with over one third in France. http://www.biomedcentral....

Thursday, July 24, 2014 *** Protocol for further laboratory investigations into the distribution of infectivity of Atypical BSE SCIENTIFIC REPORT OF EFSA New protocol for Atypical BSE investigations http://bse-atypical.blogs...

P.66: Transport of CWD prions in Alberta soils Alsu Kuznetsova1, Debbie McKenzie2, Tariq Siddique1, and Judd Aiken2 1University of Alberta; Department of Renewable Resources; Edmonton, Canada; 2University of Alberta; Centre for Prions and Protein Folding Diseases; Edmonton, Canada

P.161: Prion soil binding may explain efficient horizontal CWD transmission Nathaniel Denkers1, Davin Henderson1, Shannon Bartelt-Hunt2, Jason Bartz3, and Edward Hoover1 1Colorado State University; Fort Collins, Colorado USA; 2University of Nebraska-Lincoln; Omaha, Nebraska USA; 3Creighton University; Omaha, Nebraska USA Conclusion. Silty clay loam exhibits highly efficient prion binding, inferring a durable environmental reservoir, and an efficient mechanism for indirect horizontal CWD transmission. https://prion2015.files.w...

Tuesday, June 23, 2015 Report on the monitoring and testing of ruminants for the presence of transmissible spongiform encephalopathies (TSEs) in the EU in 2013 Final version 18 May 2015 http://transmissiblespong...

end...TSS
No competing interests declared.

see full text;

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

Terry S. Singeltary Sr., 03 Jul 2015 at 16:53 GMT

TUESDAY, NOVEMBER 17, 2009 

SEAC NEW RESULTS ON IDIOPATHIC BRAINSTEM NEURONAL CHROMATOLYSIS (IBNC) FROM THE VETERINARY LABORATORIES AGENCY (VLA) SEAC 103/1

SPONGIFORM ENCEPHALOPATHY ADVISORY COMMITTEE

Draft minutes of the 102nd meeting held on 4th March 2009 Nobel House, 17 Smith Square, London SW1P 3JR

snip...

ITEM 5 – NEW RESULTS ON IDIOPATHIC BRAINSTEM NEURONAL CHROMATOLYSIS (IBNC) FROM THE VETERINARY LABORATORIES AGENCY (VLA)

14. Dr Martin Jeffrey (Veterinary Laboratories Agency (VLA)) presented an overview of a recent publication on Idiopathic Brainstem Neuronal Chromatolysis (IBNC)4. During the period 1987 to 1992, VLA examined the neuropathology of whole brains from all submissions made under the BSE orders in Scotland to look for possible strain variation or mutation of the existing BSE strain or other prion diseases of cattle. During the course of these investigations a small number of cases of IBNC were identified. Abnormally accumulated prion protein was found in the brains of the IBNC cases. Dr Jeffrey suggested that these findings indicate that the range of prion disease pathology may be wider than thought or that abnormalities of prion protein gene expression might be associated with brain lesions unconnected with classical prion diseases.

15. A member noted that IBNC appears to be a rare disease and the prevalence of IBNC seems not to have increased over time. Dr Jeffrey noted that the detection rate of IBNC is dependent on the design of cattle surveillance and it is possible that cases of IBNC may be missed by current surveillance. Nevertheless, it is likely that IBNC is rare. A member suggested that should transmission 

3 Truscott, J.E. and Ferguson, N. M. (2008) Control of scrapie in the UK sheep population. Epidemiology and Infection, 8 August 2008, on-line, doi: 10.1017/S0950268808001064. 4Jeffrey et al. (2008) Idiopathic Brainstem Neuronal Chromatolysis (IBNC): a novel prion protein related disorder of cattle? 4, 38.

experiments using bovinised, ovinised and humanised mice indicate that IBNC is transmissible, the ability of surveillance to detect IBNC should be examined. It would be important to conduct transmission experiments using brains from IBNC cases proven, as far as possible, not to have BSE.

16. A member asked about whether differential diagnosis was made on BSE suspect cases that subsequently were found not to be BSE. Dr Yvonne Boyd (Defra) noted that currently less than 10% of suspected BSE suspect cases were subsequently confirmed. Defra was funding a research project to examine a number of clinical BSE suspects subsequently found not to be BSE, but routine differential diagnosis was not carried out on all such cases. Dr Jim Hope (VLA) added that such cases were not specifically investigated for the presence of other neurological diseases; only the presence of spongiform change and the properties of the prion protein were assessed. However, obvious differential diagnoses were reported, e.g. meningioencephalitis, if detected.

17. A member noted that even though prion protein accumulation was evident in IBNC cases, the form of prion protein produced was protease sensitive, indicating that IBNC may not be a form of TSE. Dr Jeffrey explained that, from the biochemical studies conducted, an abnormally folded, but protease sensitive, form of prion protein could not be ruled out.

18. A member asked if any of the cases of IBNC examined showed evidence of possible co-infection with classical BSE. Dr Jeffrey replied that as the neuropathological lesions of IBNC and BSE differed, co-infection should be detectable. However, no evidence of co-infection had been detected. A member suggested it may be possible to re-examine archived BSE brains for the possibility of IBNC co-infection to establish whether IBNC is indeed a rare disease. Dr Jeffrey noted that as IBNC predominantly affects older cattle, the age of the cattle brains would be a factor in such an investigation.

19. A member asked if the sequence of the prion protein gene had been studied in the IBNC cases as this can influence the pathogenesis and neuropathology of prion diseases. Dr Jeffrey replied that no detailed studies had been conducted.

20. A member noted that IBNC appeared to be a neurological condition and therefore the specified risk material controls would confer public health protection should IBNC be zoonotic.

21. The Chair summarised the discussion, noting that IBNC appears to pose no immediate high risk to human health. It appears to be a rare disease, although current surveillance may miss cases. It cannot be concluded if IBNC is transmissible, or not. Transmission studies using material from IBNC cases proven not to be BSE, that include transgenic mice lines, are important. Studies to investigate whether IBNC is associated with a normal or abnormal form of prion protein could be informative.

ITEM 6 – UPDATE ON CJD EPIDEMIOLOGY

snip...see;



Saturday, February 28, 2009

NEW RESULTS ON IDIOPATHIC BRAINSTEM NEURONAL CHROMATOLYSIS "All of the 15 cattle tested showed that the brains had abnormally accumulated PrP" 2009


Wednesday, October 08, 2008 

Idiopathic Brainstem Neuronal Chromatolysis (IBNC): a novel prion protein related disorder of cattle?


Identification of Idiopathic Brainstem Neuronal Chromatolysis (IBNC) in group 5 samples

 One of the 21 samples identified in group 5 was shown to have IBNC following histological investigation (03/00002) (figure 8). Concurrently, we investigated the PrP distribution in known cases of IBNC (Jeffrey et al 2008; “Idiopathic Brainstem Neuronal Chromatolysis (IBNC): a novel prion protein related disorder of cattle?” BMC Vet Res. 2008 Sep 30;4:38. The IHC and histology profile of this case was very similar to that of the known IBNC cases.

 Investigation of the distribution and molecular characteristics of PrP from known IBNC

 See also: Idiopathic Brainstem Neuronal Chromatolysis (IBNC): a novel prion protein related disorder of cattle?

Jeffrey M, Perez BB, Martin S, Terry L, González L.

BMC Vet Res. 2008 Sep 30;4:38

Further investigations demonstrated that 57% the assays performed on the confirmed IBNC samples, using the 0.3 Bio-Rad TeSeE assay (n=42), gave values above those of the test kit control and also the BSE negative brain pool control.

Half brains from six IBNC affected animals were retrieved from the TSE archive alongside the brainstem from a seventh animal. The cortex, brainstem, cerebellum and midbrain from these brains were sub-sampled and the adapted Bio-Rad TeSeE EIA, IDEXX Herdchek and Western Blot protocols applied to these tissues, in order to determine whether they could represent a form of atypical BSE. These samples had previously been found to be negative using the commercial Bio-Rad EIA and re-testing using this assay and the IDEXX Herdchek assay confirmed their negative status. When assayed using the adapted Bio-Rad protocol at 0.3µl/ml PK, 24/42 (57%) of the sample assays performed gave values above those of the test kit control and also the BSE negative brain pool control. Values above twice that of the calculated cut-off levels were found for each case but not for each brain site

No PrPres was detected when Western blotting these samples at either 20 or 4µl/ml PK but a signal was detected on the gels when blotted at the 0.12 and 0.3µl/ml PK levels. At 0.12µl/ml PK the IBNC samples were indistinguishable from the negative controls but at the 0.3µl/ml level more PrPres was detected in the IBNC cases than in the controls with each of the antibodies tested (SHA31, F99, SAF84 and P4). Illustrations of the F99 blot are shown in the paper. Other data not shown.

These data suggest that IBNC affected cattle abnormally express or accumulate PrP in brain and that the abnormal PrP is not strongly resistant to protease digestion. The results suggest that either the range of prion diseases is still wider than previously thought or that abnormalities of prion protein expression may be associated with brain lesions unconnected with prion disorders. Biochemical and transmission studies are planned in order to investigate further (under SE2014).


Acta Microbiologica et Immunologica Hungarica

Volume/Issue: Volume 56: Issue 1

Broadening spectrum of bovine spongiform encephalopathies

DOI: https://doi.org/10.1556/amicr.56.2009.1.3 Page Count: 53–60 Publication Date: 01 Mar 2009 Online Publication Date: 26 Mar 2009 Article Category: Research Article

Until recently the etiology of bovine spongiform encephalopathy (BSE) was considered uniform. The infectious agent was thought to be a single strain of prion (posttranslationally altered form of normal prion protein: PrPSc) retaining its biochemical and biological characteristics during interspecies transmission. However, alternate PrPSc signatures through large-scale screening have recently been detected. In addition, genetic alterations governing susceptibility to prion infection and a mutation (E211K) capable of eliciting spontaneous BSE have been demonstrated. Thus, the spectrum of BSEs have broadened and three PrPSc variants (BSE-C, BSE-H and BSE-L) are now defined. Moreover, a new condition resembling BSE, idiopathic brainstem neuronal chromatolysis (IBNC), has been described that may also turn out to be a prion disease. Since one of the new BSE variants, L-type BSE, proved highly pathogenic detection and further characterization of the new conditions are essential.

REFERENCES




Research Project: Investigation of a PRNP Polymorphism on Susceptibility to Bovine Spongiform Encephalopathy (BSE) Location: Virus and Prion Research

Project Number: 5030-32000-114-08-S Project Type: Non-Assistance Cooperative Agreement

Start Date: Sep 1, 2019 End Date: Aug 31, 2023

Objective: Determine the relationship of a genetic polymorphism in the prion protein gene of an Alabama beef cattle herd to atypical L-type BSE.

Approach: The research effort being proposed will involve two specific objectives, and include: 1) an evaluation of the genotype of older cattle with this potential phenotype; and, 2) development of a cohort of calves that are homozygous wild-type (R/R), heterozygous (R/T) and homozygous affected (T/T). Specific Objective #2 will be accomplished through selective breeding of R/T genotype cattle at the farm of origin and utilization of advanced reproductive technologies developed by Cooperator. First, estrus synchronization/timed artificial insemination (TAI) techniques on R/T cattle will be performed. Starting in January 2020, between 40-50 cattle with the R/T genotype will be separated from the other members of the herd into distinct breeding groups, and setup for estrus synchronization-TAI using semen from bulls who we already have confirmed have the genetic polymorphism. Following TAI, two clean-up bulls who have been confirmed to possess the R/T genotype will be used to breed 20-25 cows each for a 60-day breeding season. Second, superovulation-embryo transfer or superovulation-in vitro fertilization of select R/T cattle will be performed at Cooperator's facility. One of the cattle to be utilized in the advanced reproductive technologies program is the sole-surviving offspring of the original 2017 Alabama BSE cow.Three (3) cows known to have the R/T genotype will be setup for embryo transfer (ET) or in vitro fertilization (IVF). We anticipate performing ET once monthly or IVF twice monthly on these 3 cows and freezing the resulting high quality grade embryos. Once calves are born either to dams (farm of origin breedings) or recipients (ET or IVF), they will be tested for the PRNP polymorphism and raised with their dams until weaning at approximately 8 months of age when 30 calves (10 each with R/R, R/T, and T/T genotype) will be transferred to USDA-ARS for susceptibility studies.



THURSDAY, JULY 20, 2017 

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


LET'S take a closer look at this new prionpathy or prionopathy, and then let's look at the g-h-BSEalabama mad cow. 

This new prionopathy in humans? 

the genetic makeup is IDENTICAL to the g-h-BSEalabama mad cow, the only _documented_ mad cow in the world to date like this, ......

wait, it get's better. this new prionpathy is killing young and old humans, with LONG DURATION from onset of symptoms to death, and the symptoms are very similar to nvCJD victims, OH, and the plaques are very similar in some cases too, bbbut, it's not related to the g-h-BSEalabama cow, 

WAIT NOW, it gets even better, the new human prionpathy that they claim is a genetic TSE, has no relation to any gene mutation in that family. daaa, ya think it could be related to that mad cow with the same genetic make-up ??? 

there were literally tons and tons of banned mad cow protein in Alabama in commerce, and none of it transmitted to cows, and the cows to humans there from ??? r i g h t $$$ 

ALABAMA MAD COW g-h-BSEalabama 

In this study, we identified a novel mutation in the bovine prion protein gene (Prnp), called E211K, of a confirmed BSE positive cow from Alabama, United States of America. 

This mutation is identical to the E200K pathogenic mutation found in humans with a genetic form of CJD. 

This finding represents the first report of a confirmed case of BSE with a potential pathogenic mutation within the bovine Prnp gene. 

We hypothesize that the bovine Prnp E211K mutation most likely has caused BSE in "the approximately 10-year-old cow" carrying the E221K mutation. 



Saturday, August 14, 2010 

BSE Case Associated with Prion Protein Gene Mutation (g-h-BSEalabama) and VPSPr PRIONPATHY (see mad cow feed in COMMERCE IN ALABAMA...TSS) 


her healthy calf also carried the mutation (J. A. Richt and S. M. Hall PLoS Pathog. 4, e1000156; 2008). 

This raises the possibility that the disease could occasionally be genetic in origin. Indeed, the report of the UK BSE Inquiry in 2000 suggested that the UK epidemic had most likely originated from such a mutation and argued against the scrapierelated assumption. Such rare potential pathogenic PRNP mutations could occur in countries at present considered to be free of BSE, such as Australia and New Zealand. So it is important to maintain strict surveillance for BSE in cattle, with rigorous enforcement of the ruminant feed ban (many countries still feed ruminant proteins to pigs). Removal of specified risk material, such as brain and spinal cord, from cattle at slaughter prevents infected material from entering the human food chain. Routine genetic screening of cattle for PRNP mutations, which is now available, could provide additional data on the risk to the public. Because the point mutation identified in the Alabama animals is identical to that responsible for the commonest type of familial (genetic) CJD in humans, it is possible that the resulting infective prion protein might cross the bovine-human species barrier more easily. Patients with vCJD continue to be identified. The fact that this is happening less often should not lead to relaxation of the controls necessary to prevent future outbreaks. Malcolm A. Ferguson-Smith Cambridge University Department of Veterinary Medicine, Madingley Road, Cambridge CB3 0ES, UK e-mail:maf12@cam.ac.uk Jürgen A. Richt College of Veterinary Medicine, Kansas State University, K224B Mosier Hall, Manhattan, Kansas 66506-5601, USA NATURE|Vol 457|26 February 2009


LET'S take a closer look at this new prionpathy or prionopathy, and then let's look at the g-h-BSEalabama mad cow. 

This new prionopathy in humans? 

the genetic makeup is IDENTICAL to the g-h-BSEalabama mad cow, the only _documented_ mad cow in the world to date like this, ......

wait, it get's better. this new prionpathy is killing young and old humans, with LONG DURATION from onset of symptoms to death, and the symptoms are very similar to nvCJD victims, OH, and the plaques are very similar in some cases too, bbbut, it's not related to the g-h-BSEalabama cow, 

WAIT NOW, it gets even better, the new human prionpathy that they claim is a genetic TSE, has no relation to any gene mutation in that family. daaa, ya think it could be related to that mad cow with the same genetic make-up ??? 

there were literally tons and tons of banned mad cow protein in Alabama in commerce, and none of it transmitted to cows, and the cows to humans there from ??? r i g h t $$$ 

ALABAMA MAD COW g-h-BSEalabama 

In this study, we identified a novel mutation in the bovine prion protein gene (Prnp), called E211K, of a confirmed BSE positive cow from Alabama, United States of America. 

This mutation is identical to the E200K pathogenic mutation found in humans with a genetic form of CJD. 

This finding represents the first report of a confirmed case of BSE with a potential pathogenic mutation within the bovine Prnp gene. 

We hypothesize that the bovine Prnp E211K mutation most likely has caused BSE in "the approximately 10-year-old cow" carrying the E221K mutation. 



Saturday, August 14, 2010 

BSE Case Associated with Prion Protein Gene Mutation (g-h-BSEalabama) and VPSPr PRIONPATHY (see mad cow feed in COMMERCE IN ALABAMA...TSS) 


her healthy calf also carried the mutation (J. A. Richt and S. M. Hall PLoS Pathog. 4, e1000156; 2008). This raises the possibility that the disease could occasionally be genetic in origin. Indeed, the report of the UK BSE Inquiry in 2000 suggested that the UK epidemic had most likely originated from such a mutation and argued against the scrapierelated assumption. Such rare potential pathogenic PRNP mutations could occur in countries at present considered to be free of BSE, such as Australia and New Zealand. So it is important to maintain strict surveillance for BSE in cattle, with rigorous enforcement of the ruminant feed ban (many countries still feed ruminant proteins to pigs). Removal of specified risk material, such as brain and spinal cord, from cattle at slaughter prevents infected material from entering the human food chain. Routine genetic screening of cattle for PRNP mutations, which is now available, could provide additional data on the risk to the public. Because the point mutation identified in the Alabama animals is identical to that responsible for the commonest type of familial (genetic) CJD in humans, it is possible that the resulting infective prion protein might cross the bovine-human species barrier more easily. Patients with vCJD continue to be identified. The fact that this is happening less often should not lead to relaxation of the controls necessary to prevent future outbreaks. Malcolm A. Ferguson-Smith Cambridge University Department of Veterinary Medicine, Madingley Road, Cambridge CB3 0ES, UK e-mail: maf12@cam.ac.uk Jürgen A. Richt College of Veterinary Medicine, Kansas State University, K224B Mosier Hall, Manhattan, Kansas 66506-5601, USA NATURE|Vol 457|26 February 2009


Thursday, July 24, 2014 

*** Protocol for further laboratory investigations into the distribution of infectivity of Atypical BSE SCIENTIFIC REPORT OF EFSA New protocol for Atypical BSE investigations 


Saturday, August 14, 2010 

BSE Case Associated with Prion Protein Gene Mutation (g-h-BSEalabama) and VPSPr PRIONPATHY 

(see mad cow feed in COMMERCE IN ALABAMA...TSS) 


WEDNESDAY, APRIL 24, 2019 

***> USDA Announces Atypical Bovine Spongiform Encephalopathy Detection Aug 29, 2018 A Review of Science 2019 <***


TUESDAY, AUGUST 28, 2018 

USDA finds BSE infection in Florida cow 08/28/18 6:43 PM


WEDNESDAY, AUGUST 29, 2018 

USDA Announces Atypical Bovine Spongiform Encephalopathy Detection USDA 08/29/2018 10:00 AM EDT


WEDNESDAY, AUGUST 29, 2018 

Transmissible Spongiform Encephalopathy TSE Prion Atypical BSE Confirmed Florida Update USA August 28, 2018


THURSDAY, DECEMBER 17, 2020
 
THE MAD COW BSE TSE PRION THAT STOLE CHRISTMAS DECEMBER 2003, WHAT REALLY HAPPENED, A REVIEW 2020 


WEDNESDAY, JULY 31, 2019 

The agent of transmissible mink encephalopathy passaged in sheep is similar to BSE-L


O.4.3

Spread of BSE prions in cynomolgus monkeys (Macaca fascicularis) after oral transmission

Edgar Holznagel1, Walter Schulz-Schaeffer2, Barbara Yutzy1, Gerhard Hunsmann3, Johannes Loewer1 1Paul-Ehrlich-Institut, Federal Institute for Sera and Vaccines, Germany; 2Department of Neuropathology, Georg-August University, Göttingen, Germany, 3Department of Virology and Immunology, German Primate Centre, Göttingen, Germany

Background: BSE-infected cynomolgus monkeys represent a relevant animal model to study the pathogenesis of variant Creutzfeldt-Jacob disease (vCJD).

Objectives: To study the spread of BSE prions during the asymptomatic phase of infection in a simian animal model.

Methods: Orally BSE-dosed macaques (n=10) were sacrificed at defined time points during the incubation period and 7 orally BSE-dosed macaques were sacrificed after the onset of clinical signs. Neuronal and non-neuronal tissues were tested for the presence of proteinase-K-resistant prion protein (PrPres) by western immunoblot and by paraffin-embedded tissue (PET) blot technique.

Results: In clinically diseased macaques (5 years p.i. + 6 mo.), PrPres deposits were widely spread in neuronal tissues (including the peripheral sympathetic and parasympathetic nervous system) and in lymphoid tissues including tonsils. In asymptomatic disease carriers, PrPres deposits could be detected in intestinal lymph nodes as early as 1 year p.i., but CNS tissues were negative until 3 – 4 years p.i. Lumbal/sacral segments of the spinal cord and medulla oblongata were PrPres positive as early as 4.1 years p.i., whereas sympathetic trunk and all thoracic/cervical segments of the spinal cord were still negative for PrPres. However, tonsil samples were negative in all asymptomatic cases.

Discussion: There is evidence for an early spread of BSE to the CNS via autonomic fibres of the splanchnic and vagus nerves indicating that trans-synaptical spread may be a time-limiting factor for neuroinvasion. Tonsils were predominantly negative during the main part of the incubation period indicating that epidemiological vCJD screening results based on the detection of PrPres in tonsil biopsies may mostly tend to underestimate the prevalence of vCJD among humans.

P.4.23

Transmission of atypical BSE in humanized mouse models

Liuting Qing1, Wenquan Zou1, Cristina Casalone2, Martin Groschup3, Miroslaw Polak4, Maria Caramelli2, Pierluigi Gambetti1, Juergen Richt5, Qingzhong Kong1 1Case Western Reserve University, USA; 2Instituto Zooprofilattico Sperimentale, Italy; 3Friedrich-Loeffler-Institut, Germany; 4National Veterinary Research Institute, Poland; 5Kansas State University (Previously at USDA National Animal Disease Center), USA

Background: Classical BSE is a world-wide prion disease in cattle, and the classical BSE strain (BSE-C) has led to over 200 cases of clinical human infection (variant CJD). Atypical BSE cases have been discovered in three continents since 2004; they include the L-type (also named BASE), the H-type, and the first reported case of naturally occurring BSE with mutated bovine PRNP (termed BSE-M). The public health risks posed by atypical BSE were largely undefined.

Objectives: To investigate these atypical BSE types in terms of their transmissibility and phenotypes in humanized mice. Methods: Transgenic mice expressing human PrP were inoculated with several classical (C-type) and atypical (L-, H-, or Mtype) BSE isolates, and the transmission rate, incubation time, characteristics and distribution of PrPSc, symptoms, and histopathology were or will be examined and compared.

Results: Sixty percent of BASE-inoculated humanized mice became infected with minimal spongiosis and an average incubation time of 20-22 months, whereas only one of the C-type BSE-inoculated mice developed prion disease after more than 2 years. Protease-resistant PrPSc in BASE-infected humanized Tg mouse brains was biochemically different from bovine BASE or sCJD. PrPSc was also detected in the spleen of 22% of BASE-infected humanized mice, but not in those infected with sCJD. Secondary transmission of BASE in the humanized mice led to a small reduction in incubation time. The atypical BSE-H strain is also transmissible with distinct phenotypes in the humanized mice, but no BSE-M transmission has been observed so far.

Discussion: Our results demonstrate that BASE is more virulent than classical BSE, has a lymphotropic phenotype, and displays a modest transmission barrier in our humanized mice.

BSE-H is also transmissible in our humanized Tg mice.

The possibility of more than two atypical BSE strains will be discussed.

Supported by NINDS NS052319, NIA AG14359, and NIH AI 77774.


P03.137

Transmission of BSE to Cynomolgus Macaque, a Non-human Primate; Development of Clinical Symptoms and Tissue Distribution of PrPSC

Yamakawa, Y1; Ono, F2; Tase, N3; Terao, K3; Tannno, J3; Wada, N4; Tobiume, M5; Sato, Y5; Okemoto-Nakamura, Y1; Hagiwara, K1; Sata, T5 1National Institure of Infectious diseases, Cell biology and Biochemistry, Japan; 2Corporation for Production and Research Laboratory Primates., Japan; 3National Institure of Biomedical Innovation, Tsukuba Primate Reserch Center, Japan; 4Yamauchi Univ., Veterinary Medicine, Japan; 5National Institure of Infectious diseases, Pathology, Japan

Two of three cynomolgus monkeys developed abnormal neuronal behavioral signs at 30-(#7) and 28-(#10) months after intracerebral inoculation of 200ul of 10% brain homogenates of BSE affected cattle (BSE/JP6). Around 30 months post inoculation (mpi), they developed sporadic anorexia and hyperekplexia with squeal against environmental stimulations such as light and sound. Tremor, myoclonic jerk and paralysis became conspicuous during 32 to 33-mpi, and symptoms become worsened according to the disease progression. Finally, one monkey (#7) fell into total paralysis at 36-mpi. This monkey was sacrificed at 10 days after intensive veterinary care including infusion and per oral supply of liquid food. The other monkey (#10) had to grasp the cage bars to keep an upright posture caused by the sever ataxia. This monkey was sacrificed at 35-mpi. EEG of both monkeys showed diffuse slowing. PSD characteristic for sporadic CJD was not observed in both monkeys. The result of forearm movement test showed the hypofunction that was observed at onset of clinical symptoms. Their cognitive function determined by finger maze test was maintained at the early stage of sideration. However, it was rapidly impaired followed by the disease progression. Their autopsied tissues were immunochemically investigated for the tissue distribution of PrPSc. Severe spongiform change in the brain together with heavy accumulation of PrPSc having the type 2B/4 glycoform profile confirmed successful transmission of BSE to Cynomolgus macaques. Granular and linear deposition of PrPSC was detected by IHC in the CNS of both monkeys. At cerebral cortex, PrPSC was prominently accumulated in the large plaques. Sparse accumulation of PrPSc was detected in several peripheral nerves of #7 but not in #10 monkey, upon the WB analysis. Neither #7 nor #10 monkey accumulated detectable amounts of PrPSc in their lymphatic organs such as tonsil, spleen, adrenal grands and thymus although PrPSc was barely detected in the submandibular lymph node of #7 monkey. Such confined tissue distribution of PrPSc after intracerebral infection with BSE agent is not compatible to that reported on the Cynomolgus macaques infected with BSE by oral or intra-venous (intra-peritoneal) routs, in which PrPSc was accumulated at not only CNS but also widely distributed lymphatic tissues.

P04.27

Experimental BSE Infection of Non-human Primates: Efficacy of the Oral Route

Holznagel, E1; Yutzy, B1; Deslys, J-P2; Lasmézas, C2; Pocchiari, M3; Ingrosso, L3; Bierke, P4; Schulz-Schaeffer, W5; Motzkus, D6; Hunsmann, G6; Löwer, J1 1Paul-Ehrlich-Institut, Germany; 2Commissariat à l´Energie Atomique, France; 3Instituto Superiore di Sanità, Italy; 4Swedish Institute for Infectious Disease control, Sweden; 5Georg August University, Germany; 6German Primate Center, Germany

Background: In 2001, a study was initiated in primates to assess the risk for humans to contract BSE through contaminated food. For this purpose, BSE brain was titrated in cynomolgus monkeys.

Aims: The primary objective is the determination of the minimal infectious dose (MID50) for oral exposure to BSE in a simian model, and, by in doing this, to assess the risk for humans. Secondly, we aimed at examining the course of the disease to identify possible biomarkers.

Methods: Groups with six monkeys each were orally dosed with lowering amounts of BSE brain: 16g, 5g, 0.5g, 0.05g, and 0.005g. In a second titration study, animals were intracerebrally (i.c.) dosed (50, 5, 0.5, 0.05, and 0.005 mg).

Results: In an ongoing study, a considerable number of high-dosed macaques already developed simian vCJD upon oral or intracerebral exposure or are at the onset of the clinical phase. However, there are differences in the clinical course between orally and intracerebrally infected animals that may influence the detection of biomarkers.

Conclusions: Simian vCJD can be easily triggered in cynomolgus monkeys on the oral route using less than 5 g BSE brain homogenate. The difference in the incubation period between 5 g oral and 5 mg i.c. is only 1 year (5 years versus 4 years). However, there are rapid progressors among orally dosed monkeys that develop simian vCJD as fast as intracerebrally inoculated animals.

The work referenced was performed in partial fulfilment of the study “BSE in primates“ supported by the EU (QLK1-2002-01096).


Simian vCJD can be easily triggered in cynomolgus monkeys on the oral route using less than 5 g BSE brain homogenate.


***> 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 amplification (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.


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.

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


Detection of PrPBSE and prion infectivity in the ileal Peyer’s patch of young calves as early as 2 months after oral challenge with classical bovine spongiform encephalopathy 

Ivett Ackermann1 , Anne Balkema‑Buschmann1 , Reiner Ulrich2 , Kerstin Tauscher2 , James C. Shawulu1 , Markus Keller1 , Olanrewaju I. Fatola1 , Paul Brown3 and Martin H. Groschup1* 

Abstract 

In classical bovine spongiform encephalopathy (C-BSE), an orally acquired prion disease of cattle, the ileal Peyer’s patch (IPP) represents the main entry port for the BSE agent. In earlier C-BSE pathogenesis studies, cattle at 4–6 months of age were orally challenged, while there are strong indications that the risk of infection is highest in young animals. In the present study, unweaned calves aged 4–6 weeks were orally challenged to determine the earli‑ est time point at which newly formed PrPBSE and BSE infectivity are detectable in the IPP. For this purpose, calves were culled 1 week as well as 2, 4, 6 and 8 months post-infection (mpi) and IPPs were examined for BSE infectivity using a bovine PrP transgenic mouse bioassay, and for PrPBSE by immunohistochemistry (IHC) and protein misfolding cyclic amplifcation (PMCA) assays. For the frst time, BSE prions were detected in the IPP as early as 2 mpi by transgenic mouse bioassay and PMCA and 4 mpi by IHC in the follicular dendritic cells (FDCs) of the IPP follicles. These data indi‑ cate that BSE prions propagate in the IPP of unweaned calves within 2 months of oral uptake of the agent.

In summary, our study demonstrates for the frst time PrPBSE (by PMCA) and prion infectivity (by mouse bioassay) in the ileal Peyer’s patch (IPP) of young calves as early as 2 months after infection. From 4 mpi nearly all calves showed PrPBSE positive IPP follicles (by IHC), even with PrPBSE accumulation detectable in FDCs in some animals. Finally, our results confrm the IPP as the early port of entry for the BSE agent and a site of initial propagation of PrPBSE and infectivity during the early pathogenesis of the disease. Terefore, our study supports the recommendation to remove the last four metres of the small intestine (distal ileum) at slaughter, as designated by current legal requirements for countries with a controlled BSE risk status, as an essential measure for consumer and public health protection.


WE know now, and we knew decades ago, that 5.5 grams of suspect feed in TEXAS was enough to kill 100 cows.

look at the table and you'll see that as little as 1 mg (or 0.001 gm) caused 7% (1 of 14) of the cows to come down with BSE;

Risk of oral infection with bovine spongiform encephalopathy agent in primates

Corinne Ida Lasmézas, Emmanuel Comoy, Stephen Hawkins, Christian Herzog, Franck Mouthon, Timm Konold, Frédéric Auvré, Evelyne Correia, Nathalie Lescoutra-Etchegaray, Nicole Salès, Gerald Wells, Paul Brown, Jean-Philippe Deslys Summary The uncertain extent of human exposure to bovine spongiform encephalopathy (BSE)--which can lead to variant Creutzfeldt-Jakob disease (vCJD)--is compounded by incomplete knowledge about the efficiency of oral infection and the magnitude of any bovine-to-human biological barrier to transmission. We therefore investigated oral transmission of BSE to non-human primates. We gave two macaques a 5 g oral dose of brain homogenate from a BSE-infected cow. One macaque developed vCJD-like neurological disease 60 months after exposure, whereas the other remained free of disease at 76 months. On the basis of these findings and data from other studies, we made a preliminary estimate of the food exposure risk for man, which provides additional assurance that existing public health measures can prevent transmission of BSE to man.

snip...

BSE bovine brain inoculum

100 g 10 g 5 g 1 g 100 mg 10 mg 1 mg 0·1 mg 0·01 mg

Primate (oral route)* 1/2 (50%)

Cattle (oral route)* 10/10 (100%) 7/9 (78%) 7/10 (70%) 3/15 (20%) 1/15 (7%) 1/15 (7%)

RIII mice (ic ip route)* 17/18 (94%) 15/17 (88%) 1/14 (7%)

PrPres biochemical detection

The comparison is made on the basis of calibration of the bovine inoculum used in our study with primates against a bovine brain inoculum with a similar PrPres concentration that was inoculated into mice and cattle.8 *Data are number of animals positive/number of animals surviving at the time of clinical onset of disease in the first positive animal (%). The accuracy of bioassays is generally judged to be about plus or minus 1 log. ic ip=intracerebral and intraperitoneal.

Table 1: Comparison of transmission rates in primates and cattle infected orally with similar BSE brain inocula

Published online January 27, 2005


It is clear that the designing scientists must also have shared Mr Bradley’s surprise at the results because all the dose levels right down to 1 gram triggered infection.


it is clear that the designing scientists must have also shared Mr Bradleyâs surprise at the results because all the dose levels right down to 1 gram triggered infection.


 

I ask Professor Kong ;

Thursday, December 04, 2008 3:37 PM

Subject: RE: re--Chronic Wating Disease (CWD) and Bovine Spongiform Encephalopathies (BSE): Public Health Risk Assessment

IS the h-BSE more virulent than typical BSE as well, or the same as cBSE, or less virulent than cBSE? just curious.....

Professor Kong reply ;

.....snip

As to the H-BSE, we do not have sufficient data to say one way or another, but we have found that H-BSE can infect humans. I hope we could publish these data once the study is complete. Thanks for your interest.

Best regards, Qingzhong Kong, PhD Associate Professor Department of Pathology Case Western Reserve University Cleveland, OH 44106 USA 

P.4.23 Transmission of atypical BSE in humanized mouse models 

Liuting Qing1, Wenquan Zou1, Cristina Casalone2, Martin Groschup3, Miroslaw Polak4, Maria Caramelli2, Pierluigi Gambetti1, Juergen Richt5, Qingzhong Kong1 1Case Western Reserve University, USA; 2Instituto Zooprofilattico Sperimentale, Italy; 3Friedrich-Loeffler-Institut, Germany; 4National Veterinary Research Institute, Poland; 5Kansas State University (Previously at USDA National Animal Disease Center), USA

Background: Classical BSE is a world-wide prion disease in cattle, and the classical BSE strain (BSE-C) has led to over 200 cases of clinical human infection (variant CJD). Atypical BSE cases have been discovered in three continents since 2004; they include the L-type (also named BASE), the H-type, and the first reported case of naturally occurring BSE with mutated bovine PRNP (termed BSE-M). The public health risks posed by atypical BSE were argely undefined.

Objectives: To investigate these atypical BSE types in terms of their transmissibility and phenotypes in humanized mice.

Methods: Transgenic mice expressing human PrP were inoculated with several classical (C-type) and atypical (L-, H-, or Mtype) BSE isolates, and the transmission rate, incubation time, characteristics and distribution of PrPSc, symptoms, and histopathology were or will be examined and compared.

Results: Sixty percent of BASE-inoculated humanized mice became infected with minimal spongiosis and an average incubation time of 20-22 months, whereas only one of the C-type BSE-inoculated mice developed prion disease after more than 2 years. Protease-resistant PrPSc in BASE-infected humanized Tg mouse brains was biochemically different from bovine BASE or sCJD. PrPSc was also detected in the spleen of 22% of BASE-infected humanized mice, but not in those infected with sCJD. Secondary transmission of BASE in the humanized mice led to a small reduction in incubation time. The atypical BSE-H strain is also transmissible with distinct phenotypes in the humanized mice, but no BSE-M transmission has been observed so far.

Discussion: Our results demonstrate that BASE is more virulent than classical BSE, has a lymphotropic phenotype, and displays a modest transmission barrier in our humanized mice. BSE-H is also transmissible in our humanized Tg mice. The possibility of more than two atypical BSE strains will be discussed.

Supported by NINDS NS052319, NIA AG14359, and NIH AI 77774.


see full text ;


P98 The agent of H-type bovine spongiform encephalopathy associated with E211K prion protein polymorphism transmits after oronasal challenge 

Greenlee JJ (1), Moore SJ (1), and West Greenlee MH (2) (1) United States Department of Agriculture, Agricultural Research Service, National Animal Disease Center, Virus and Prion Research Unit, Ames, IA, United States (2) Department of Biomedical Sciences, Iowa State University College of Veterinary Medicine, Ames, IA, United States. 

In 2006, a case of H-type bovine spongiform encephalopathy (BSE) was reported in a cow with a previously unreported prion protein polymorphism (E211K). 

The E211K polymorphism is heritable and homologous to the E200K mutation in humans that is the most frequent PRNP mutation associated with familial Creutzfeldt-Jakob disease. 

Although the prevalence of the E211K polymorphism is low, cattle carrying the K211 allele develop H-type BSE with a rapid onset after experimental inoculation by the intracranial route. 

The purpose of this study was to investigate whether the agents of H-type BSE or H-type BSE associated with the E211K polymorphism transmit to wild type cattle or cattle with the K211 allele after oronasal exposure. 

Wild type (EE211) or heterozygous (EK211) cattle were oronasally inoculated with either H-type BSE from the 2004 US Htype BSE case (n=3) or from the 2006 US H-type case associated with the E211K polymorphism (n=4) using 10% w/v brain homogenates. 

Cattle were observed daily throughout the course of the experiment for the development of clinical signs. 

At approximately 50 months post-inoculation, one steer (EK211 inoculated with E211K associated H-BSE) developed clinical signs including inattentiveness, loss of body condition, weakness, ataxia, and muscle fasciculations and was euthanized. 

Enzyme immunoassay confirmed that abundant misfolded protein was present in the brainstem, and immunohistochemistry demonstrated PrPSc throughout the brain. 

Western blot analysis of brain tissue from the clinically affected steer was consistent with the E211K H-type BSE inoculum. 

With the experiment currently at 55 months post-inoculation, no other cattle in this study have developed clinical signs suggestive of prion disease. This study demonstrates that the H-type BSE agent is transmissible by the oronasal route. 

These results reinforce the need for ongoing surveillance for classical and atypical BSE to minimize the risk of potentially infectious tissues entering the animal or human food chains. 

PRION 2018 CONFERENCE ABSTRACT

Prion Conference 2018

WEDNESDAY, AUGUST 15, 2018 

***> The agent of H-type bovine spongiform encephalopathy associated with E211K prion protein polymorphism transmits after oronasal challenge


57 The experiment which might have determined whether BSE and scrapie were caused by the same agent (ie, the feeding of natural scrapie to cattle) was never undertaken in the UK. 

It was, however, performed in the USA in 1979, when it was shown that cattle inoculated with the scrapie agent endemic in the flock of Suffolk sheep at the United States Department of Agriculture in Mission, Texas, developed a TSE quite unlike BSE. 32 

The findings of the initial transmission, though not of the clinical or neurohistological examination, were communicated in October 1988 to Dr Watson, Director of the CVL, following a visit by Dr Wrathall, one of the project leaders in the Pathology Department of the CVL, to the United States Department of Agriculture. 33 

The results were not published at this point, since the attempted transmission to mice from the experimental cow brain had been inconclusive. 

The results of the clinical and histological differences between scrapie-affected sheep and cattle were published in 1995. 

Similar studies in which cattle were inoculated intracerebrally with scrapie inocula derived from a number of scrapie-affected sheep of different breeds and from different States, were carried out at the US National Animal Disease Centre. 34 

The results, published in 1994, showed that this source of scrapie agent, though pathogenic for cattle, did not produce the same clinical signs of brain lesions characteristic of BSE..

32 Clark, W., Hourrigan, J. and Hadlow, W. (1995) Encephalopathy in Cattle Experimentally Infected with the Scrapie Agent, American Journal of Veterinary Research, 56, 606-12

33 YB88/10.00/1.1 


Technical Abstract:

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

***>This work provides evidence that multiple scrapie strains exist in U.S. sheep. 


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


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


- 59-

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.


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

Title: Comparison of two US sheep scrapie isolates supports identification as separate strains

Authors

item Moore, Sarah - item Smith, Jodi item West Greenlee, Mary - item Nicholson, Eric item Richt, Juergen item Greenlee, Justin

Submitted to: Veterinary Pathology Publication Type: Peer Reviewed Journal Publication Acceptance Date: December 22, 2015 Publication Date: N/A

Interpretive Summary: Scrapie is a fatal disease of sheep and goats that causes damaging changes in the brain. The infectious agent is an abnormal protein called a prion that has misfolded from its normal state. Whether or not a sheep will get scrapie is determined primarily by their genetics. Furthermore, different scrapie strains exist that may result in a different expression of disease such as shorter incubation periods, unusual clinical signs, or unique patterns of lesions within the brain. This study evaluated two U.S. scrapie isolates in groups of sheep with varying susceptibilities to scrapie. Our data indicates that there are differences in incubation periods, sheep genotype susceptibilities, and lesion profiles that support designating these scrapie isolates as unique strains. The identification of a new scrapie strain in the United States means that control measures, methods of decontamination, and the potential for transmission to other species may need to be reevaluated. This information is useful to sheep farmers and breeders that are selectively breeding animals with genotypes resistant to the most prevalent strain of scrapie and could impact future regulations for the control of scrapie in the United States. Technical Abstract: Scrapie is a naturally occurring transmissible spongiform encephalopathy (TSE) of sheep and goats. There are different strains of sheep scrapie that are associated with unique molecular, transmission, and phenotype characteristics, but very little is known about the potential presence of scrapie strains within sheep in the US. Scrapie strain and PRNP genotype could both affect susceptibility, potential for transmission, incubation period, and control measures required for eliminating scrapie from a flock. Here we evaluate two US scrapie isolates, No. 13-7 and x124, after intranasal inoculation to compare clinical signs, incubation periods (IP), spongiform lesions, and patterns of PrPSc deposition in sheep with scrapie-susceptible PRNP genotypes (QQ171). After inoculation with x124, susceptibility and IP were associated with valine at codon 136 (V136) of the prion protein: VV136 had short IPs (6.9 months), AV136 sheep were 11.9 months, and AA136 sheep did not develop scrapie. All No.13-7 inoculated sheep developed scrapie with IP’s of 20.1 months for AA136 sheep, 22.8 months for AV136 sheep, and 26.7 months for VV136 sheep. Patterns of immunoreactivity in the brain were influenced by challenge isolate and host genotype. Differences in PrPSc profiles versus isolate were most striking when examining brains from sheep with the VV136 genotype. In summary, intranasal inoculation with isolates x124 and No. 13-7 resulted in differences in IP, sheep genotype susceptibility, and PrPSc profile that support designation as separate strains.

Last Modified: 6/6/2016


31

Appendix I VISIT TO USA - OR A E WRATHALL — INFO ON BSE AND SCRAPIE

Dr Clark lately of the scrapie Research Unit, Mission Texas has

successfully transmitted ovine and caprine scrapie to cattle. The

experimental results have not been published but there are plans to do

this. This work was initiated in 1978. A summary of it is:-

Expt A 6 Her x Jer calves born in 1978 were inoculated as follows with

a 2nd Suffolk scrapie passage:-

i/c 1ml; i/m, 5ml; s/c 5ml; oral 30ml.

1/6 went down after 48 months with a scrapie/BSE-like disease.

Expt B 6 Her or Jer or HxJ calves were inoculated with angora Goat

virus 2/6 went down similarly after 36 months.

Expt C Mice inoculated from brains of calves/cattle in expts A & B were resistant, only 1/20 going down with scrapie and this was the reason given for not publishing.

Diagnosis in A, B, C was by histopath. No reports on SAF were given.

Dr Warren Foote indicated success so far in eliminating scrapie in offspring from experimentally— (and naturally) infected sheep by ET. He had found difficulty in obtaining embryos from naturally infected sheep (cf SPA).

Prof. A Robertson gave a brief accout of BSE. The us approach was to

32

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.

BSE was not reported in USA.

4. Scrapie incidents (ie affected flocks) have shown a dramatic increase since 1978. In 1953 when the National Control scheme was started there were 10-14 incidents, in 1978 - 1 and in 1988 so far 60.

5. Scrapie agent was reported to have been isolated from a solitary fetus.

6. A western blotting diagnostic technique (? on PrP) shows some promise.

7. Results of a questionnaire sent to 33 states on the subject of the national sheep scrapie programme survey indicated

17/33 wished to drop it

6/33 wished to develop it

8/33 had few sheep and were neutral

Information obtained from Dr Wrathall‘s notes of a meeting of the u.s.

Animal Health Association at Little Rock, Arkansas Nov. 1988.

33

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. ...


also see hand written notes ;


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.



*** The discovery of previously unrecognized prion diseases in both humans and animals (i.e., Nor98 in small ruminants) demonstrates that the range of prion diseases might be wider than expected and raises crucial questions about the epidemiology and strain properties of these new forms. We are investigating this latter issue by molecular and biological comparison of VPSPr, GSS and Nor98.

VARIABLY PROTEASE-SENSITVE PRIONOPATHY IS TRANSMISSIBLE ...price of prion poker goes up again $

OR-10: Variably protease-sensitive prionopathy is transmissible in bank voles

Romolo Nonno,1 Michele Di Bari,1 Laura Pirisinu,1 Claudia D’Agostino,1 Stefano Marcon,1 Geraldina Riccardi,1 Gabriele Vaccari,1 Piero Parchi,2 Wenquan Zou,3 Pierluigi Gambetti,3 Umberto Agrimi1 1Istituto Superiore di Sanità; Rome, Italy; 2Dipartimento di Scienze Neurologiche, Università di Bologna; Bologna, Italy; 3Case Western Reserve University; Cleveland, OH USA

Background. Variably protease-sensitive prionopathy (VPSPr) is a recently described “sporadic”neurodegenerative disease involving prion protein aggregation, which has clinical similarities with non-Alzheimer dementias, such as fronto-temporal dementia. Currently, 30 cases of VPSPr have been reported in Europe and USA, of which 19 cases were homozygous for valine at codon 129 of the prion protein (VV), 8 were MV and 3 were MM. A distinctive feature of VPSPr is the electrophoretic pattern of PrPSc after digestion with proteinase K (PK). After PK-treatment, PrP from VPSPr forms a ladder-like electrophoretic pattern similar to that described in GSS cases. The clinical and pathological features of VPSPr raised the question of the correct classification of VPSPr among prion diseases or other forms of neurodegenerative disorders. Here we report preliminary data on the transmissibility and pathological features of VPSPr cases in bank voles.

Materials and Methods. Seven VPSPr cases were inoculated in two genetic lines of bank voles, carrying either methionine or isoleucine at codon 109 of the prion protein (named BvM109 and BvI109, respectively). Among the VPSPr cases selected, 2 were VV at PrP codon 129, 3 were MV and 2 were MM. Clinical diagnosis in voles was confirmed by brain pathological assessment and western blot for PK-resistant PrPSc (PrPres) with mAbs SAF32, SAF84, 12B2 and 9A2.

Results. To date, 2 VPSPr cases (1 MV and 1 MM) gave positive transmission in BvM109. Overall, 3 voles were positive with survival time between 290 and 588 d post inoculation (d.p.i.). All positive voles accumulated PrPres in the form of the typical PrP27–30, which was indistinguishable to that previously observed in BvM109 inoculated with sCJDMM1 cases.

In BvI109, 3 VPSPr cases (2 VV and 1 MM) showed positive transmission until now. Overall, 5 voles were positive with survival time between 281 and 596 d.p.i.. In contrast to what observed in BvM109, all BvI109 showed a GSS-like PrPSc electrophoretic pattern, characterized by low molecular weight PrPres. These PrPres fragments were positive with mAb 9A2 and 12B2, while being negative with SAF32 and SAF84, suggesting that they are cleaved at both the C-terminus and the N-terminus. Second passages are in progress from these first successful transmissions.

Conclusions. Preliminary results from transmission studies in bank voles strongly support the notion that VPSPr is a transmissible prion disease. Interestingly, VPSPr undergoes divergent evolution in the two genetic lines of voles, with sCJD-like features in BvM109 and GSS-like properties in BvI109.

The discovery of previously unrecognized prion diseases in both humans and animals (i.e., Nor98 in small ruminants) demonstrates that the range of prion diseases might be wider than expected and raises crucial questions about the epidemiology and strain properties of these new forms. We are investigating this latter issue by molecular and biological comparison of VPSPr, GSS and Nor98.


Tuesday, August 03, 2010

Variably protease-sensitive prionopathy: A new sporadic disease of the prion protein

http://creutzfeldt-jakob-disease.blogspot.com/2010/08/variably-protease-sensitive-prionopathy.html

Monday, August 9, 2010

Variably protease-sensitive prionopathy: A new sporadic disease of the prion protein or just more PRIONBALONEY ?

http://prionunitusaupdate2008.blogspot.com/2010/08/variably-protease-sensitive-prionopathy.html

***+++***

Thursday, July 10, 2008

A Novel Human Disease with Abnormal Prion Protein Sensitive to Protease update July 10, 2008 Friday, June 20, 2008

http://cjdmadcowbaseoct2007.blogspot.com/2008/07/novel-human-disease-with-abnormal-prion.html

Monday, August 9, 2010

National Prion Disease Pathology Surveillance Center Cases Examined (July 31, 2010)

(please watch and listen to the video and the scientist speaking about atypical BSE and sporadic CJD and listen to Professor Aguzzi)

http://prionunitusaupdate2008.blogspot.com/2010/08/national-prion-disease-pathology.html

***>8The sporadic cases include 4020 cases of sporadic Creutzfeldt-Jakob disease (sCJD), 71 cases of Variably Protease-Sensitive Prionopathy (VPSPr) and 35 cases of sporadic Fatal Insomnia (sFI). <***

USA Tables of Cases Examined National Prion Disease Pathology Surveillance Center Cases Examined¹ Updated quarterly.

Last updated on: October 8th, 2020

Year Total Referrals² Prion Disease Sporadic Familial Iatrogenic vCJD

1999 & earlier 382 231 200 27 3 0

2000 145 102 90 12 0 0

2001 209 118 110 8 0 0

2002 241 144 124 18 2 0

2003 259 160 137 21 2 0

2004 316 181 164 16 0 1³

2005 327 178 156 21 1 0

2006 365 179 159 17 1 2⁴

2007 374 210 191 19 0 0

2008 384 221 205 16 0 0

2009 397 231 210 20 1 0

2010 401 246 218 28 0 0

2011 392 238 214 24 0 0

2012 413 244 221 23 0 0

2013 416 258 223 34 1 0

2014 355 208 185 21 1 1⁵

2015 401 263 243 20 0 0

2016 396 277 248 29 0 0

2017 375 266 247 19 0 0

2018 309 223 204 18 1 0

2019 422 274 252 21 0 0

2020 252 159 125 11 1 0

TOTAL 75316 46117 41268 4439 14 4

1Listed based on the year of death or, if not available, on the year of referral; 

2Cases with suspected prion disease for which brain tissue was submitted; 

3Disease acquired in the United Kingdom; 

4Disease acquired in the United Kingdom in one case and in Saudi Arabia in the other; 

5Disease possibly acquired in a Middle Eastern or Eastern European country; 

6Includes 12 cases in which the diagnosis is pending, and 19 inconclusive cases; 

7Includes 24 (1 from 1986, 1 from 2019, 22 from 2020) cases with type determination pending in which the diagnosis of vCJD has been excluded. 

8The sporadic cases include 4020 cases of sporadic Creutzfeldt-Jakob disease (sCJD), 71 cases of Variably Protease-Sensitive Prionopathy (VPSPr) and 35 cases of sporadic Fatal Insomnia (sFI). 

9Total does not include 277 Familial cases diagnosed by blood test only.


SUNDAY, MARCH 10, 2019 

***> National Prion Disease Pathology Surveillance Center Cases Examined¹ Updated Feb 1, 2019 Variably protease-sensitive prionopathy VPSPr


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

Greetings Friends, Neighbors, and Colleagues,



Saturday, February 2, 2019 

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

snip... 

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

REVIEW 

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

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

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

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

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

Thursday, March 8, 2018 

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


2020

cwd scrapie pigs oral routes 

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

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

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

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




***> Wednesday, January 23, 2019 

***> CFIA SFCR Guidance on Specified risk material (SRM) came into force on January 15, 2019 <***


MONDAY, NOVEMBER 30, 2020 

***> REPORT OF THE MEETING OF THE OIE SCIENTIFIC COMMISSION FOR ANIMAL DISEASES Paris, 9–13 September 2019 BSE, TSE, PRION<***

***> see updated concerns with atypical BSE from feed and zoonosis...terry


TUESDAY, SEPTEMBER 29, 2020 

ISO's Updated 22442 Animal Tissue Standards — What Changed? TSE Prion!


WEDNESDAY, MAY 29, 2019 

Incomplete inactivation of atypical scrapie following recommended autoclave decontamination procedures USDA HERE'S YOUR SIGN!


WEDNESDAY, OCTOBER 28, 2020 

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


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

PLEASE NOTE;

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

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

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


SUNDAY, OCTOBER 11, 2020 

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


THURSDAY, SEPTEMBER 24, 2020 

The emergence of classical BSE from atypical/ Nor98 scrapie


FRIDAY, OCTOBER 23, 2020 

Scrapie TSE Prion Zoonosis Zoonotic, what if?


THURSDAY, DECEMBER 17, 2020 

Exposure Risk of Chronic Wasting Disease in Humans 


USDA FDA MAD COW FEED BAN THAT NEVER WAS, A REVIEW 2020

mad cow feed in commerce USA, post mad cow feed ban 1997!

10 years post mad cow feed ban August 1997 

10,000,000+ LBS. of PROHIBITED BANNED MAD COW FEED I.E. BLOOD LACED MBM IN COMMERCE USA 2007 

Date: March 21, 2007 at 2:27 pm PST 

RECALLS AND FIELD CORRECTIONS: VETERINARY MEDICINES -- CLASS II PRODUCT 

Bulk cattle feed made with recalled Darling's 85% Blood Meal, Flash Dried, Recall # V-024-2007 CODE Cattle feed delivered between 01/12/2007 and 01/26/2007 RECALLING FIRM/MANUFACTURER Pfeiffer, Arno, Inc, Greenbush, WI. by conversation on February 5, 2007. 

Firm initiated recall is ongoing. 

REASON Blood meal used to make cattle feed was recalled because it was cross- contaminated with prohibited bovine meat and bone meal that had been manufactured on common equipment and labeling did not bear cautionary BSE statement. 

VOLUME OF PRODUCT IN COMMERCE 42,090 lbs. DISTRIBUTION WI 

___________________________________ 

PRODUCT 

Custom dairy premix products: 

MNM ALL PURPOSE Pellet, 

HILLSIDE/CDL Prot- Buffer Meal, 

LEE, M.-CLOSE UP PX Pellet, 

HIGH DESERT/ GHC LACT Meal, 

TATARKA, 

M CUST PROT Meal, 

SUNRIDGE/CDL PROTEIN Blend, 

LOURENZO, K PVM DAIRY Meal, 

DOUBLE B DAIRY/GHC LAC Mineral, 

WEST PIONT/GHC CLOSEUP Mineral, 

WEST POINT/GHC LACT Meal, 

JENKS, 

J/COMPASS PROTEIN Meal, 

COPPINI - 8# SPECIAL DAIRY Mix, 

GULICK, L-LACT Meal (Bulk), 

TRIPLE J - PROTEIN/LACTATION, 

ROCK CREEK/GHC MILK Mineral, 

BETTENCOURT/GHC S.SIDE MK-MN, 

BETTENCOURT #1/GHC MILK MINR, 

V&C DAIRY/GHC LACT Meal, 

VEENSTRA, F/GHC LACT Meal, 

SMUTNY, A- BYPASS ML W/SMARTA, 

Recall # V-025-2007 

CODE The firm does not utilize a code - only shipping documentation with commodity and weights identified. 

RECALLING FIRM/MANUFACTURER Rangen, Inc, Buhl, ID, by letters on February 13 and 14, 2007. 

Firm initiated recall is complete. 

REASON Products manufactured from bulk feed containing blood meal that was cross contaminated with prohibited meat and bone meal and the labeling did not bear cautionary BSE statement. 

VOLUME OF PRODUCT IN COMMERCE 9,997,976 lbs. 

DISTRIBUTION ID and NV 

END OF ENFORCEMENT REPORT FOR MARCH 21, 2007 


RECALLS AND FIELD CORRECTIONS: VETERINARY MEDICINE -- CLASS II

______________________________ 

PRODUCT

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

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

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

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

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

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

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

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

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

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

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

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

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

CODE

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

RECALLING FIRM/MANUFACTURER

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

REASON

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

VOLUME OF PRODUCT IN COMMERCE

125 tons

DISTRIBUTION

AL and FL 

______________________________

snip...too much to list here see;

THURSDAY, DECEMBER 17, 2020 

THE MAD COW BSE TSE PRION THAT STOLE CHRISTMAS DECEMBER 2003, WHAT REALLY HAPPENED, A REVIEW 2020 


Idiopathic Brain Stem Neuronal Chromatolysis (IBNC)

 29. Mr Bradley described the results of transmission studies in mice from brains of two cows with IBNC (paper SEAC 19/8). At the previous meeting of SEAC, and at the review of R&D, it had been announced that there was no clinical observation of a scrapie-like disease in mice: this information had proved to be incorrect for a number of reasons. Of the mice inoculated with brain tissue from the first cow, there had 
been mild transient clinical signs. one had shown equivocal lesions of SE but PrP studies had proved negative. From the second cow there were two definite cases of SE though the lesion distribution and incubation period were not the same as seen in mice inoculated with brain from BSE cases or any characterised strain of scrapie. The lesions in these two mice were PrP positive. There was no obvious evidence of any mix up though one possible area of cross-contamination was during the necropsy in the Perth VIC. More evidence would be needed and further transmission studies to validate the results and proposals were put forward for further study. 

30. The Committee noted that the results were unusual .. They questioned whether there could be coincidental BSE infection or contamination with scrapie. Dr Tyrrell noted that the feeling of the Committee was that this did not represent a new agent but it was important to be prepared to say something publicly about these findings. A suggested line to take was that these were scientifically unpublishable results but in line with the policy of openness they would be made publicly available and further work done to test their validity. Since the BSE precautions were applied to IBNC cases. human health was protected. Further investigations should be carried out on isolations from brains of IBNC cases with removal of the brain and subsequent handling under strict conditions to avoid the risk of any contamination. 

31. Mr Bradley informed the Committee that the CVO had informed the CMO about the IBNC results and the transmission from retina and he. like the Committee was satisfied that the controls already in place or proposed were adequate. Research priorities 

32. The Committee reviewed the list of priorities attached at Appendix 2 to the previous minutes. It was agreed that the work on BSE in native-born Portuguese cattle was of higher priority than that on post 1991 BABs with unusual lesions. Although of lower priority. transmission of the BSE isolate from a French cow imported into the UK was of interest, but as with the IBNC cases was compromised because brain removal was not under conditions intended to prevent cross- contamination. A future indigenous French case would be more appropriate. Comparisons with UK BSE might help to give a better understanding of the origin of the BSE outbreak. Whatever the outcome, the results would be interesting. These two items should be promoted to three stars. Dr Kimberlin said he would also like to see higher priority given to transmission of marmoset-passaged BSE as it would give worthwhile information on the stability of the BSE agent after passage in a primate. 

33. After some discussion. it was agreed that it was valuable to classify research priorities both on scientific and policy grounds . Research Update 

 34. Dr Bradley provided an update on NPU transmission studies provided by Dr Taylor and Dr Manson. The information they had provided (attached at Appendix 1) did not give a clear picture but the message appeared to be that some sheep and goats showing positive clinical signs of disease were not being confirmed pathologically and others with positive pathology showed no clinical signs. However the picture was incomplete and confused and would need to be clarified for the next meeting. A summary of updates on other research projects is attached at Appendix 2. Date of next meeting 

 35. The next meeting will be held at 10.30 am on Friday, g September 1995 in Room 125a Skipton House. 

6 July 1995 


Published: 30 September 2008

Idiopathic Brainstem Neuronal Chromatolysis (IBNC): a novel prion protein related disorder of cattle?

Martin Jeffrey, Belinda Baquero Perez, Stuart Martin, Linda Terry & Lorenzo González BMC Veterinary Research volume 4, Article number: 38 (2008) Cite this article

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Abstract

Background

The epidemic form of Bovine Spongiform Encephalopathy (BSE) is generally considered to have been caused by a single prion strain but at least two strain variants of cattle prion disorders have recently been recognized. An additional neurodegenerative condition, idiopathic brainstem neuronal chromatolysis and hippocampal sclerosis (IBNC), a rare neurological disease of adult cattle, was also recognised in a sub-set of cattle submitted under the BSE Orders in which lesions of BSE were absent. Between the years of 1988 and 1991 IBNC occurred in Scotland with an incidence of 7 cases per 100,000 beef suckler cows over the age of 6 years.

Results

When the brains of 15 IBNC cases were each tested by immunohistochemistry, all showed abnormal labelling for prion protein (PrP). Immunohistological labelling for PrP was also present in the retina of a single case available for examination. The pattern of PrP labelling in brain is distinct from that seen in other ruminant prion diseases and is absent from brains with other inflammatory conditions and from normal control brains. Brains of IBNC cattle do not reveal abnormal PrP isoforms when tested by the commercial BioRad or Idexx test kits and do not reveal PrPres when tested by Western blotting using stringent proteinase digestion methods. However, some weakly protease resistant isoforms of PrP may be detected when tissues are examined using mild proteinase digestion techniques.

Discussion This study shows that the novel condition of cattle previously identified as IBNC and recognized from within the BSE suspect submissions, abnormally expresses or accumulates PrP in brain and retina. However, this abnormal PrP is not composed of isoforms that are strongly resistant to protease digestion suggesting that it is not present in the form of large aggregates.

Immunohistochemical demonstration of PrP labelling and increased levels of PrP mRNA have previously been described in adult humans affected with acute vascular disorders, in infants with perinatal hypoxia and experimental infarction of rodents [9]. These findings are considered to represent upregulation of PrP expression which encompasses part of the oxidative stress response of neurons. We have also observed increased PrP in the cytoplasm of neurons undergoing ischaemic degeneration in a variety of sheep encephalopathies. Though ischaemic neuronal degeneration is not a feature of IBNC, nevertheless, the presence of PrP within the cytoplasm of some chromatolytic and degenerate neurons of IBNC affected cattle is consistent with the idea that stressed neurons may respond by increasing PrP expression.

Though present in only two cows, the pattern of PrP accumulation within the granule cell layer of the cerebellum is morphologically similar to that reported by several authors for Nor 98 types of the transmissible spongiform encephalopathy or prion disease of sheep [3, 10]. The PrP accumulation within the plexiform layers of the eye is similar to that of both natural scrapie [11] and of Nor 98 (MJ personal observations). However the majority type of PrP labelling that occurred in all IBNC cases was found within the neuropil, mainly in the rostral neuraxis and cerebrum, the nature of which is previously unreported in cattle or in any other prion disorder. This novel pattern of labelling appears to correspond to a rarefaction or fine microvacuolation of neuropil as seen on standard HE stained sections.

Pathological, biochemical and bioassay data all suggest that the epidemic form of cattle BSE is a single strain. However, recent large scale EU wide surveillance for BSE has led to the unexpected discovery of rare and hitherto unknown prion diseases of cattle. Small numbers of atypical forms of cattle prion diseases have now been recognized from several European countries, in the USA and Japan and can be distinguished by histological, molecular and transmission characteristics [12–14]. Bovine Amyloidotic Spongiform Encephalopathy (BASE) was the first of these novel cattle prion disorders to be recognized and was characterized by the presence of numerous small amyloid deposits of abnormal PrP. It was initially discovered in three aged Italian cattle [1] and has subsequently been transmitted to transgenic mice [13, 14]. A further variant of a cattle prion disease affecting cows between 8 and 15 years was initially recognized in France [2] and has also been transmitted to mice. BSE and these novel cattle prion diseases can be distinguished using biochemical and molecular methods and are now classified as C, H and L type isolates [12]. H type and L type (BASE) isolates are defined according to the higher and lower positions of the unglycosylated PrPres bands in Western blots, respectively, when compared to the position of the corresponding band in classical BSE (C type) isolates [12]. L type cases formerly classified as BASE, have a distinctive glycopattern in which monoglycoslyated PrPres predominates compared to BSE [12, 14]. While IBNC cases are on average older than BSE cases they occupy a similar age class of cattle to that of H and L type cattle prion diseases, but IBNC can be readily distinguished from H, L and C type cattle prion disease by morphologic pathology and by the absence of PrPres under stringent conditions of protease digestion.

Not all abnormal PrPres isoforms detected from brains of animals affected with prion disease are resistant to stringent protease digestion. The PrPres of two sheep of the ARR/ARR PrP genotype affected with a classical scrapie-like disease accumulated unusually protease sensitive isoforms of PrP [15]. Similarly, the transmissible prion disease of sheep known as Nor 98 and related conditions (often referred to as atypical scrapie) also have weakly protease resistant PrPres [3, 16]. Nor 98 does not appear to transmit readily to other sheep under field conditions: it also does not transmit to conventional mice although it does readily transmit disease to one strain of transgenic mouse which substantially over-expresses the VRQ allele of sheep PrP [16, 17]. The transgenic PG14 mouse also has PrPres which is even more readily digested than that found in Nor 98 but this prion protein disorder has not so far been successfully transmitted [18]. The biochemical analyses of limited numbers of IBNC cases clearly shows that highly aggregated forms of protease resistant PrP are not present in brain tissue. However, when the data from the ELISA and immunoblot tests using mild protease digestion are compared with that of normal control material it is possible that smaller aggregates of PrP molecules may be present.

Conclusion

The study shows that a distinctive neurological disorder of cattle, which has some clinical similarities to BSE, is associated with abnormal PrP labelling in brain but the pathology and biochemistry of IBNC are distinct from BSE. The study is important either because it raises the possibility of a significant increase in the scope of prion disease or because it demonstrates that widespread and consistent PrP alterations may not be confined to prion diseases. Further studies, including transmission experiments, are needed to establish whether IBNC is a condition in which prion protein is abnormally regulated or it is yet a further example of an infectious cattle prion disease.

Conclusion

The present results indicate that there are changes in PrP expression or accumulation in the neurodegenerative cattle disorder known as IBNC. The pathology and biochemistry of IBNC are quite distinct from that of other prion diseases of cattle and other species but the pathology does include grey matter spongiform changes. The transmissibility of this disorder is undetermined. These results are interesting as they show that either the range of prion diseases and associated pathology is still wider than previously thought or that substantial abnormalities of prion protein expression may be associated with brain lesions unconnected with classical prion diseases. Further biochemical and transmission studies are needed to determine which of these possibilities is correct.



1985

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... 




''Further investigations should be carried out on isolations from brains of IBNC cases with removal of the brain and subsequent handling under strict conditions to avoid the risk of any contamination.''

this dog don't hunt no more, same old song and dance;

gotton so screwed up, by not being able to tell a sheep brain from a cow brain;

© DEFRA 2002 Item 3- Scrapie Brain pool experiments- Update on current position and audits of samples 3.1 Members were updated on experiments conducted at the Institute of Animal Health (IAH) to examine a pool of scrapie brains collected in the early 1990 s for evidence of BSE. SEAC had previously recommended that the material should be examined by DNA analysis to assess whether the pooled brain material may have been contaminated with bovine tissue. The Laboratory of the Government Chemist (LGC) had been asked to perform the work. Their results were completely unexpected as the analysis detected only bovine material in the sample. SEAC had intended to meet on the 19 October to Agreed version consider the experiment in detail. However, in view of the result, the meeting was cancelled.


 Executive Summary An audit of the sample handling procedures at IAH-E was carried out on 24 October 2001 at the request of the Department of the Environment, Food and Rural Affairs (DEFRA), by a team of two UKAS auditors. The scope of the audit was limited to the traceability of cow and sheep brain samples used in several experiments relating to transmissible spongiform encephalopathy (TSE) agents. In particular, the team focused on the audit trail of samples that had been sent to LGC, Teddington, the audit trail of brains collected in 1990/92 by Veterinary Investigation Centres and the audit trail for archived material held by IAH-E. In addition the audit team evaluated the IAH-E procedures against the specific requirements for sampling handling of international standard, ISO 17025 and identified opportunities for improvement. The audit established that there was no formal documented quality system covering this work at IAH-E and that record keeping was inadequate to give confidence in the chain of custody of samples used in the various rendering, genotyping and strain typing experiments audited. It was not possible to establish clear traceability between the samples that had been used in the individual experiments carried out by IAH-E or IAH-C with those analysed at LGC or with those that had been collected in 1990/92. The sample handling procedures covered by this audit at IAH-E did not meet the requirements of ISO 17025.


explaining the brain mixup blunder;

An Investigation of the Substitution of Scrapie Brain Pool Samples A report for DEFRA November 2001

Risk Solutions Page 19 

Why did the experimenters not notice that they were working with cow brains not sheep brains? 

The simple answer is because for the most part they were working with brain pool macerate (minced brain material) not brains. It is not credible that staff collecting brains at VICs would have uniformly supplied cow brains or cow brain parts in mistake for sheep. We have interviewed staff at VICs and we understand from the VLA that records do not support the possibility that significant numbers of cow brains were sent to PDM in place of sheep brains. It is also very unlikely that the people preparing the scrapie brain pool would not have noticed if they were for the most part handling cow brains or cow brain parts in place of sheep brains. We cannot rule out the possibility that some cow brain material entered the brain pool at this stage but it is not feasible that the majority of the material was bovine. The substitution, if substitution occurred, must have involved brain pool macerate or rendered products. 

Why can t the results of the experiments tell us what material was used? 

The experiments had a number of features that make the results of the mouse bioassay difficult to interpret unambiguously and lead to the possibility that substitution of the samples would be difficult to detect by examining the results of the experiments: 

1. The original experiments were not designed to determine whether BSE was present in sheep. Reasonable efforts were taken to ensure that the brain pool remained free from D5055 02 Issue 1 Risk Solutions Page 20 contamination during preparation but the level of control applied during the earlier experiments (272R and 372R) was not to the standard applied later. 

2. Mouse bioassay as a method of diagnosing TSEs is not based on a full understanding of biochemical and physical processes. It is an empirical technique that has been widely applied, for example to show v-CJD is similar to BSE and different from scrapie. It is a complex process and the results need to be interpreted by experts. It can take several years to generate a firm result. The principal data collected in the experiments are lesion profiles (patterns of lesions in the mice brains) and incubation period (time from injection of mice to onset of clinical symptoms. The type of TSE is identified by comparing the results with those of known provenance. There is no good agreed test of sameness of lesion profile , so in marginal cases we are reduced to using subjective observations of the form somewhat similar and interpretation is difficult. The incubation times in principle give a more objective signal, but the effect of concentration has to be controlled. The mouse bioassay data that we understand has been collected and analysed at each stage of the experiments is summarised in Table 4.1. Several features of these experiments are not commonly encountered in mouse bioassay of TSEs and this makes determining the origin of the original material from the experimental results extremely difficult. 

They include: 

a. Mouse bioassay is generally carried out on individual brains; experience of working with brain pools is very limited. 

b. The BBP exhibited a low titre of infectivity, which can confound interpretation of results. 

c. The BBP comprised bovine brains with the hindbrains removed. By contrast most of the BSE strain typing has been carried out on the hindbrains, which may give a different pattern of results. 

d. The 272R titrations used a different strain of mice than the 372R titrations, so direct comparison of the resulting lesion profiles cannot be made. 

e. The 246 experiments used brain pool which was in an unsatisfactorily autolysed state. 

f. The strain typing data collected (incubation time and lesion profiles) are very sparse. 

Judging the sameness or difference of samples is a less challenging task for strain typing than identifying a strain and it may be possible to compare data from the 246 experiments with both the 272R and 372R experiments to determine whether the samples are similar or clearly different. However, the data are sparse and the result is unlikely to be clear cut. Much of this work is currently unpublished.


RESPONSE TO THE UKAS REPORT FROM THE INSTITUTE FOR ANIMAL HEALTH

The Institute is concerned, therefore, that the authors of this UKAS report may have based their findings on an unrepresentative and limited examination of procedures in place at IAH-E.




DEFRA Department for Environment, Food & Rural Affairs

Area 307, London, SW1P 4PQ Telephone: 0207 904 6000 Direct line: 0207 904 6287 E-mail: h.mcdonagh.defra.gsi.gov.uk

GTN: FAX:

Mr T S Singeltary P.O. Box Bacliff Texas USA 77518

21 November 2001

Dear Mr Singeltary

TSE IN HOUNDS

Thank you for e-mail regarding the hounds survey. I am sorry for the long delay in responding.

As you note, the hound survey remains unpublished. However the Spongiform Encephalopathy Advisory Committee (SEAC), the UK Government's independent Advisory Committee on all aspects related to BSE-like disease, gave the hound study detailed consideration at their meeting in January 1994. As a summary of this meeting published in the BSE inquiry noted, the Committee were clearly concerned about the work that had been carried out, concluding that there had clearly been problems with it, particularly the control on the histology, and that it was more or less inconclusive. However was agreed that there should be a re-evaluation of the pathological material in the study.

Later, at their meeting in June 95, The Committee re-evaluated the hound study to see if any useful results could be gained from it. The Chairman concluded that there were varying opinions within the Committee on further work. It did not suggest any further transmission studies and thought that the lack of clinical data was a major weakness.

Overall, it is clear that SEAC had major concerns about the survey as conducted. As a result it is likely that the authors felt that it would not stand up to r~eer review and hence it was never published. As noted above, and in the detailed minutes of the SEAC meeting in June 95, SEAC considered whether additional work should be performed to examine dogs for evidence of TSE infection. Although the Committee had mixed views about the merits of conducting further work, the Chairman noted that when the Southwood Committee made their recommendation to complete an assessment of possible spongiform disease in dogs, no TSEs had been identified in other species and hence dogs were perceived as a high risk population and worthy of study. However subsequent to the original recommendation, made in 1990, a number of other species had been identified with TSE ( e.g. cats) so a study in hounds was less critical. For more details see- http://www.bseinquiry.gov.uk/files/yb/1995/06/21005001.pdf 


As this study remains unpublished, my understanding is that the ownership of the data essentially remains with the original researchers. Thus unfortunately, I am unable to help with your request to supply information on the hound survey directly. My only suggestion is that you contact one of the researchers originally involved in the project, such as Gerald Wells. He can be contacted at the following address.

Dr Gerald Wells, Veterinary Laboratories Agency, New Haw, Addlestone, Surrey, KT 15 3NB, UK

You may also wish to be aware that since November 1994 all suspected cases of spongiform encephalopathy in animals and poultry were made notifiable. Hence since that date there has been a requirement for vets to report any suspect SE in dogs for further investigation. To date there has never been positive identification of a TSE in a dog.

I hope this is helpful

Yours sincerely 4

HUGH MCDONAGH BSE CORRESPONDENCE SECTION

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

HOUND SURVEY I am sorry, but I really could have been a co-signatory of Gerald's minute. I do NOT think that we can justify devoting any resources to this study, especially as larger and more important projects such as the pathogenesis study will be quite demanding. If there is a POLITICAL need to continue with the examination of hound brains then it should be passed entirely to the VI Service. J W WILESMITH Epidemiology Unit 18 October 1991 Mr. R Bradley cc: Mr. G A H Wells 


see new url;


3.3. Mr R J Higgins in conjunction with Mr G A Wells and Mr A C Scott would by the end of the year, indentify the three brains that were from the ''POSITIVE'' end of the lesion spectrum. 


see new url;


Thursday, July 24, 2014 

*** Protocol for further laboratory investigations into the distribution of infectivity of Atypical BSE SCIENTIFIC REPORT OF EFSA New protocol for Atypical BSE investigations 


Thursday, July 24, 2014 

*** Protocol for further laboratory investigations into the distribution of infectivity of Atypical BSE SCIENTIFIC REPORT OF EFSA New protocol for Atypical BSE investigations 


Saturday, August 14, 2010 

BSE Case Associated with Prion Protein Gene Mutation (g-h-BSEalabama) and VPSPr PRIONPATHY 

(see mad cow feed in COMMERCE IN ALABAMA...TSS) 


MONDAY, DECEMBER 14, 2020 

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


cwd scrapie pigs oral routes 

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

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

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

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




Friday, December 14, 2012 

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

snip..... 

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

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

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

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

The amount of animal PAP that is of deer and/or elk origin imported from the USA to GB can not be determined, however, as it is not specified in TRACES. 

It may constitute a small percentage of the 8412 kilos of non-fish origin processed animal proteins that were imported from US into GB in 2011. 

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

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

snip..... 

36% in 2007 (Almberg et al., 2011). In such areas, population declines of deer of up to 30 to 50% have been observed (Almberg et al., 2011). In areas of Colorado, the prevalence can be as high as 30% (EFSA, 2011). The clinical signs of CWD in affected adults are weight loss and behavioural changes that can span weeks or months (Williams, 2005). In addition, signs might include excessive salivation, behavioural alterations including a fixed stare and changes in interaction with other animals in the herd, and an altered stance (Williams, 2005). These signs are indistinguishable from cervids experimentally infected with bovine spongiform encephalopathy (BSE). Given this, if CWD was to be introduced into countries with BSE such as GB, for example, infected deer populations would need to be tested to differentiate if they were infected with CWD or BSE to minimise the risk of BSE entering the human food-chain via affected venison. snip..... The rate of transmission of CWD has been reported to be as high as 30% and can approach 100% among captive animals in endemic areas (Safar et al., 2008). 

snip..... 

In summary, in endemic areas, there is a medium probability that the soil and surrounding environment is contaminated with CWD prions and in a bioavailable form. In rural areas where CWD has not been reported and deer are present, there is a greater than negligible risk the soil is contaminated with CWD prion. snip..... In summary, given the volume of tourists, hunters and servicemen moving between GB and North America, the probability of at least one person travelling to/from a CWD affected area and, in doing so, contaminating their clothing, footwear and/or equipment prior to arriving in GB is greater than negligible... For deer hunters, specifically, the risk is likely to be greater given the increased contact with deer and their environment. However, there is significant uncertainty associated with these estimates. 

snip..... 

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

snip..... 


***> READ THIS VERY, VERY, CAREFULLY, AUGUST 1997 MAD COW FEED BAN WAS A SHAM, AS I HAVE STATED SINCE 1997! 3 FAILSAFES THE FDA ET AL PREACHED AS IF IT WERE THE GOSPEL, IN TERMS OF MAD COW BSE DISEASE IN USA, AND WHY IT IS/WAS/NOT A PROBLEM FOR THE USA, and those are; 

BSE TESTING (failed terribly and proven to be a sham) 

BSE SURVEILLANCE (failed terribly and proven to be a sham) 

BSE 589.2001 FEED REGULATIONS (another colossal failure, and proven to be a sham) 

these are facts folks. trump et al just admitted it with the feed ban. 

see; 

FDA Reports on VFD Compliance 

John Maday 

August 30, 2019 09:46 AM VFD-Form 007 (640x427) 

Before and after the current Veterinary Feed Directive rules took full effect in January, 2017, the FDA focused primarily on education and outreach. ( John Maday ) Before and after the current Veterinary Feed Directive (VFD) rules took full effect in January, 2017, the FDA focused primarily on education and outreach to help feed mills, veterinarians and producers understand and comply with the requirements. Since then, FDA has gradually increased the number of VFD inspections and initiated enforcement actions when necessary. On August 29, FDA released its first report on inspection and compliance activities. The report, titled “Summary Assessment of Veterinary Feed Directive Compliance Activities Conducted in Fiscal Years 2016 – 2018,” is available online.


SUNDAY, SEPTEMBER 1, 2019 

***> FDA Reports on VFD Compliance 


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

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

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

O.05: Transmission of prions to primates after extended silent incubation periods: Implications for BSE and scrapie risk assessment in human populations 
Emmanuel Comoy, Jacqueline Mikol, Valerie Durand, Sophie Luccantoni, Evelyne Correia, Nathalie Lescoutra, Capucine Dehen, and Jean-Philippe Deslys Atomic Energy Commission; Fontenay-aux-Roses, France 

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

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

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

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

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

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

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

=============== 

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

=============== 

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

============== 

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

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

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

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

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

PRION 2016 TOKYO

Saturday, April 23, 2016

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

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

Taylor & Francis

Prion 2016 Animal Prion Disease Workshop Abstracts

WS-01: Prion diseases in animals and zoonotic potential

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

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

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

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

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

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

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

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

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

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

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

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

snip...

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

PMID: 6997404


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

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

snip...

76/10.12/4.6


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

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

Gibbs CJ Jr, Gajdusek DC.

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

Transmission of Scrapie to the Cynomolgus Monkey (Macaca fascicularis)

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

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

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



Wednesday, February 16, 2011

IN CONFIDENCE

SCRAPIE TRANSMISSION TO CHIMPANZEES

IN CONFIDENCE


THURSDAY, AUGUST 20, 2020 

***> Why is USDA "only" BSE TSE Prion testing 25,000 samples a year? <***


MONDAY, DECEMBER 14, 2020 

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


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

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

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

O.05: Transmission of prions to primates after extended silent incubation periods: Implications for BSE and scrapie risk assessment in human populations 
Emmanuel Comoy, Jacqueline Mikol, Valerie Durand, Sophie Luccantoni, Evelyne Correia, Nathalie Lescoutra, Capucine Dehen, and Jean-Philippe Deslys Atomic Energy Commission; Fontenay-aux-Roses, France 

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

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

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

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

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

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

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

=============== 

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

=============== 

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

============== 

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

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

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

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

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

PRION 2016 TOKYO

Saturday, April 23, 2016

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

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

Taylor & Francis

Prion 2016 Animal Prion Disease Workshop Abstracts

WS-01: Prion diseases in animals and zoonotic potential

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

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

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

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

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

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

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

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

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

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

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

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

snip...

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

PMID: 6997404


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

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

snip...

76/10.12/4.6


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

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

Gibbs CJ Jr, Gajdusek DC.

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

Transmission of Scrapie to the Cynomolgus Monkey (Macaca fascicularis)

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

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

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



Wednesday, February 16, 2011

IN CONFIDENCE

SCRAPIE TRANSMISSION TO CHIMPANZEES

IN CONFIDENCE


> 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).***
Chronic Wasting Disease CWD TSE Prion aka mad deer disease zoonosis
We hypothesize that:
(1) The classic CWD prion strain can infect humans at low levels in the brain and peripheral lymphoid tissues;
(2) The cervid-to-human transmission barrier is dependent on the cervid prion strain and influenced by the host (human) prion protein (PrP) primary sequence;
(3) Reliable essays can be established to detect CWD infection in humans; and
(4) CWD transmission to humans has already occurred. We will test these hypotheses in 4 Aims using transgenic (Tg) mouse models and complementary in vitro approaches.
ZOONOTIC CHRONIC WASTING DISEASE CWD TSE PRION UPDATE
Prion 2017 Conference
First evidence of intracranial and peroral transmission of Chronic Wasting Disease (CWD) into Cynomolgus macaques: a work in progress Stefanie Czub1, Walter Schulz-Schaeffer2, Christiane Stahl-Hennig3, Michael Beekes4, Hermann Schaetzl5 and Dirk Motzkus6 1 
University of Calgary Faculty of Veterinary Medicine/Canadian Food Inspection Agency; 2Universitatsklinikum des Saarlandes und Medizinische Fakultat der Universitat des Saarlandes; 3 Deutsches Primaten Zentrum/Goettingen; 4 Robert-Koch-Institut Berlin; 5 University of Calgary Faculty of Veterinary Medicine; 6 presently: Boehringer Ingelheim Veterinary Research Center; previously: Deutsches Primaten Zentrum/Goettingen 
This is a progress report of a project which started in 2009. 21 cynomolgus macaques were challenged with characterized CWD material from white-tailed deer (WTD) or elk by intracerebral (ic), oral, and skin exposure routes. Additional blood transfusion experiments are supposed to assess the CWD contamination risk of human blood product. Challenge materials originated from symptomatic cervids for ic, skin scarification and partially per oral routes (WTD brain). Challenge material for feeding of muscle derived from preclinical WTD and from preclinical macaques for blood transfusion experiments. We have confirmed that the CWD challenge material contained at least two different CWD agents (brain material) as well as CWD prions in muscle-associated nerves. 
Here we present first data on a group of animals either challenged ic with steel wires or per orally and sacrificed with incubation times ranging from 4.5 to 6.9 years at postmortem. Three animals displayed signs of mild clinical disease, including anxiety, apathy, ataxia and/or tremor. In four animals wasting was observed, two of those had confirmed diabetes. All animals have variable signs of prion neuropathology in spinal cords and brains and by supersensitive IHC, reaction was detected in spinal cord segments of all animals. Protein misfolding cyclic amplification (PMCA), real-time quaking-induced conversion (RT-QuiC) and PET-blot assays to further substantiate these findings are on the way, as well as bioassays in bank voles and transgenic mice. 
At present, a total of 10 animals are sacrificed and read-outs are ongoing. Preclinical incubation of the remaining macaques covers a range from 6.4 to 7.10 years. Based on the species barrier and an incubation time of > 5 years for BSE in macaques and about 10 years for scrapie in macaques, we expected an onset of clinical disease beyond 6 years post inoculation. 
PRION 2017 DECIPHERING NEURODEGENERATIVE DISORDERS 
PRION 2018 CONFERENCE
Oral transmission of CWD into Cynomolgus macaques: signs of atypical disease, prion conversion and infectivity in macaques and bio-assayed transgenic mice
Hermann M. Schatzl, Samia Hannaoui, Yo-Ching Cheng, Sabine Gilch (Calgary Prion Research Unit, University of Calgary, Calgary, Canada) Michael Beekes (RKI Berlin), Walter Schulz-Schaeffer (University of Homburg/Saar, Germany), Christiane Stahl-Hennig (German Primate Center) & Stefanie Czub (CFIA Lethbridge).
To date, BSE is the only example of interspecies transmission of an animal prion disease into humans. The potential zoonotic transmission of CWD is an alarming issue and was addressed by many groups using a variety of in vitro and in vivo experimental systems. Evidence from these studies indicated a substantial, if not absolute, species barrier, aligning with the absence of epidemiological evidence suggesting transmission into humans. Studies in non-human primates were not conclusive so far, with oral transmission into new-world monkeys and no transmission into old-world monkeys. Our consortium has challenged 18 Cynomolgus macaques with characterized CWD material, focusing on oral transmission with muscle tissue. Some macaques have orally received a total of 5 kg of muscle material over a period of 2 years.
After 5-7 years of incubation time some animals showed clinical symptoms indicative of prion disease, and prion neuropathology and PrPSc deposition were detected in spinal cord and brain of some euthanized animals. PrPSc in immunoblot was weakly detected in some spinal cord materials and various tissues tested positive in RT-QuIC, including lymph node and spleen homogenates. To prove prion infectivity in the macaque tissues, we have intracerebrally inoculated 2 lines of transgenic mice, expressing either elk or human PrP. At least 3 TgElk mice, receiving tissues from 2 different macaques, showed clinical signs of a progressive prion disease and brains were positive in immunoblot and RT-QuIC. Tissues (brain, spinal cord and spleen) from these and pre-clinical mice are currently tested using various read-outs and by second passage in mice. Transgenic mice expressing human PrP were so far negative for clear clinical prion disease (some mice >300 days p.i.). In parallel, the same macaque materials are inoculated into bank voles.
Taken together, there is strong evidence of transmissibility of CWD orally into macaques and from macaque tissues into transgenic mouse models, although with an incomplete attack rate.
The clinical and pathological presentation in macaques was mostly atypical, with a strong emphasis on spinal cord pathology.
Our ongoing studies will show whether the transmission of CWD into macaques and passage in transgenic mice represents a form of non-adaptive prion amplification, and whether macaque-adapted prions have the potential to infect mice expressing human PrP.
The notion that CWD can be transmitted orally into both new-world and old-world non-human primates asks for a careful reevaluation of the zoonotic risk of CWD..
***> The notion that CWD can be transmitted orally into both new-world and old-world non-human primates asks for a careful reevaluation of the zoonotic risk of CWD. <***
Prion Conference 2018
READING OVER THE PRION 2018 ABSTRACT BOOK, LOOKS LIKE THEY FOUND THAT from this study ;
P190 Human prion disease mortality rates by occurrence of chronic wasting disease in freeranging cervids, United States
Abrams JY (1), Maddox RA (1), Schonberger LB (1), Person MK (1), Appleby BS (2), Belay ED (1) (1) Centers for Disease Control and Prevention (CDC), National Center for Emerging and Zoonotic Infectious Diseases, Atlanta, GA, USA (2) Case Western Reserve University, National Prion Disease Pathology Surveillance Center (NPDPSC), Cleveland, OH, USA..
SEEMS THAT THEY FOUND Highly endemic states had a higher rate of prion disease mortality compared to non-CWD
states.
AND ANOTHER STUDY;
P172 Peripheral Neuropathy in Patients with Prion Disease
Wang H(1), Cohen M(1), Appleby BS(1,2) (1) University Hospitals Cleveland Medical Center, Cleveland, Ohio (2) National Prion Disease Pathology Surveillance Center, Cleveland, Ohio..
IN THIS STUDY, THERE WERE autopsy-proven prion cases from the National Prion Disease Pathology Surveillance Center that were diagnosed between September 2016 to March 2017,
AND
included 104 patients. SEEMS THEY FOUND THAT The most common sCJD subtype was MV1-2 (30%), followed by MM1-2 (20%),
AND
THAT The Majority of cases were male (60%), AND half of them had exposure to wild game.
snip…
see more on Prion 2017 Macaque study from Prion 2017 Conference and other updated science on cwd tse prion zoonosis below…terry
Prion 2018 Conference
8. Even though human TSE‐exposure risk through consumption of game from European cervids can be assumed to be minor, if at all existing, no final conclusion can be drawn due to the overall lack of scientific data. In particular the US data do not clearly exclude the possibility of human (sporadic or familial) TSE development due to consumption of venison. The Working Group thus recognizes a potential risk to consumers if a TSE would be present in European cervids. It might be prudent considering appropriate measures to reduce such a risk, e.g. excluding tissues such as CNS and lymphoid tissues from the human food chain, which would greatly reduce any potential risk for consumers. However, it is stressed that currently, no data regarding a risk of TSE infections from cervid products are available.
International Conference on Emerging Diseases, Outbreaks & Case Studies & 16th Annual Meeting on Influenza March 28-29, 2018 | Orlando, USA
Qingzhong Kong
Case Western Reserve University School of Medicine, USA
Zoonotic potential of chronic wasting disease prions from cervids
Chronic wasting disease (CWD) is the prion disease in cervids (mule deer, white-tailed deer, American elk, moose, and reindeer). It has become an epidemic in North America, and it has been detected in the Europe (Norway) since 2016. The widespread CWD and popular hunting and consumption of cervid meat and other products raise serious public health concerns, but questions remain on human susceptibility to CWD prions, especially on the potential difference in zoonotic potential among the various CWD prion strains. We have been working to address this critical question for well over a decade. We used CWD samples from various cervid species to inoculate transgenic mice expressing human or elk prion protein (PrP). We found infectious prions in the spleen or brain in a small fraction of CWD-inoculated transgenic mice expressing human PrP, indicating that humans are not completely resistant to CWD prions; this finding has significant ramifications on the public health impact of CWD prions. The influence of cervid PrP polymorphisms, the prion strain dependence of CWD-to-human transmission barrier, and the characterization of experimental human CWD prions will be discussed.
Speaker Biography Qingzhong Kong has completed his PhD from the University of Massachusetts at Amherst and Post-doctoral studies at Yale University. He is currently an Associate Professor of Pathology, Neurology and Regenerative Medicine. He has published over 50 original research papers in reputable journals (including Science Translational Medicine, JCI, PNAS and Cell Reports) and has been serving as an Editorial Board Member on seven scientific journals. He has multiple research interests, including public health risks of animal prions (CWD of cervids and atypical BSE of cattle), animal modeling of human prion diseases, mechanisms of prion replication and pathogenesis, etiology of sporadic Creutzfeldt-Jacob disease (CJD) in humans, normal cellular PrP in the biology and pathology of multiple brain and peripheral diseases, proteins responsible for the α-cleavage of cellular PrP, as well as gene therapy and DNA vaccination.
SATURDAY, FEBRUARY 23, 2019 

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


TUESDAY, NOVEMBER 04, 2014 

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

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


Transmission Studies

Mule deer transmissions of CWD were by intracerebral inoculation and compared with natural cases {the following was written but with a single line marked through it ''first passage (by this route)}....TSS

resulted in a more rapidly progressive clinical disease with repeated episodes of synocopy ending in coma. One control animal became affected, it is believed through contamination of inoculum (?saline). Further CWD transmissions were carried out by Dick Marsh into ferret, mink and squirrel monkey. Transmission occurred in ALL of these species with the shortest incubation period in the ferret.

snip.... 


Prion Infectivity in Fat of Deer with Chronic Wasting Disease▿ 

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

In mice, prion infectivity was recently detected in fat. Since ruminant fat is consumed by humans and fed to animals, we determined infectivity titers in fat from two CWD-infected deer. Deer fat devoid of muscle contained low levels of CWD infectivity and might be a risk factor for prion infection of other species. 


Prions in Skeletal Muscles of Deer with Chronic Wasting Disease 

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


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

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

From: TSS 

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

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

From: "Belay, Ermias"

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

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

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

Dear Sir/Madam,

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

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

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

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


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. 


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

sporadic, spontaneous CJD, 85%+ of all human TSE, just not just happen. never in scientific literature has this been proven.

if one looks up the word sporadic or spontaneous at pubmed, you will get a laundry list of disease that are classified in such a way;



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).*** 




TUESDAY, JANUARY 21, 2020 

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


CWD TSE PRION AND ZOONOTIC, ZOONOSIS, POTENTIAL

Subject: Re: DEER SPONGIFORM ENCEPHALOPATHY SURVEY & HOUND STUDY 

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

From: Steve Dealler 

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

To: BSE-L@ References: <3daf5023 .4080804="" wt.net="">

Dear Terry,

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

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

Steve Dealler =============== 


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

BSE Inquiry Steve Dealler

Management In Confidence

BSE: Private Submission of Bovine Brain Dealler

snip...see full text;

MONDAY, FEBRUARY 25, 2019

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



P1-187 AGED CATTLE BRAIN DISPLAYSALZHEIMER’S-LIKE PATHOLOGY THATCAN BE PROPAGATED IN A PRION-LIKE MANNER
Ines Moreno-Gonzalez1, George A. Edwards, III,1, Nazaret Gamez Ruiz1,Priyadarshini Peter1, Rodrigo Morales1, Mercedes Marquez2, Marti Pumarola2,Claudio Soto1,1The University of Texas Health Science Center at Houston, Houston, TX, USA;2Animal Tissue Bank of Catalunya (BT A C), Universidad Autonoma de Barcelona, Barcelona, Spain . Contact e-mail: Ines.M.Gonzalez@uth.tmc.edu

Background: Amyloid beta (Ab) and hyperphosphorylated tau(ptau) are the proteins undergoing misfolding in Alzheimer’s dis-ease (AD). Recent studies have shown that brain homogenates rich in amyloid aggregates are able to seed the misfolding and ag-gregation of amyloidogenic proteins inducing an earlier onset of the disease in mouse models of AD. This seeding behavior is analogous to the disease transmission by propagation of prion protein misfold-ing observed in prion diseases. Prion diseases can be transmitted across species by inoculation of the misfolded prion protein from one specie into an appropriate host. For example, material from cattle affected by bovine spongiform encephalopathy can be propagate in humans inducing variant Creutzfeldt-Jakob disease.

Methods: In this study, we analyzed the presence of AD-related protein aggre-gates in the brain of old cows and investigated whether these aggregates are capable to induce pathology in animal models of AD.

Results: We observed that many of the typical hallmarks detected in human AD brains, including Ab aggregates and tangles, were present in cow brains. When cattle tissue containing Ab aggregates or ptau were intracerebrally inoculated into APP/PS1 or P301Smice, we observed an acceleration of brain misfolded protein deposition and faster cognitive impairment compared to controls. How-ever, when the material was orally inoculated, no effect was observed.

Conclusions: These results may contribute to uncover a previously unsuspected etiology surrounding some cases of spo-radic AD. However, the early and controversial stage of the field of prion-like transmission in non-prion diseases added to the artificial nature of the animal models utilized for these studies, indicate that extrapolation of the results to humans should not be done without further experiments.


P75 Determining transmissibility and proteome changes associated with abnormal bovine prionopathy 

Dudas S (1,2), Seuberlich T (3), Czub S (1,2) 

In prion diseases, it is believed that altered protein conformation encodes for different pathogenic strains. Currently 3 different strains of bovine spongiform encephalopathy (BSE) are confirmed. Diagnostic tests for BSE are able to identify animals infected with all 3 strains, however, several diagnostic laboratories have reported samples with inconclusive results which are challenging to classify. It was suggested that these may be novel strains of BSE; to determine transmissibility, brain material from index cases were inoculated into cattle. 

In the first passage, cattle were intra-cranially challenged with brain homogenate from 2 Swiss animals with abnormal prionopathy. The challenged cattle incubated for 3 years and were euthanized with no clinical signs of neurologic disease. Animals were negative when tested on validated diagnostic tests but several research methods demonstrated changes in the prion conformation in these cattle, including density gradient centrifugation and immunohistochemistry. Currently, samples from the P1 animals are being tested for changes in protein levels using 2-D Fluorescence Difference Gel Electrophoresis (2D DIGE) and mass spectrometry. It is anticipated that, if a prionopathy is present, this approach should identify pathways and targets to decipher the source of altered protein conformation. In addition, a second set of cattle have been challenged with brain material from the first passage. Ideally, these cattle will be given a sufficient incubation period to provide a definitive answer to the question of transmissibility. 

=====prion 2018=== 

Prion Conference 2018

Sunday, February 25, 2018 

PRION ROUND TABLE CONFERENCE 2018 MAY, 22-25 A REVIEW

Prion Conference 2018

Wednesday, December 16, 2020 

Expanding spectrum of prion diseases Prusiner et al


Wednesday, December 23, 2020 

Creutzfeldt–Jakob Disease with a Five-Year Clinical Course, Multicentric Cerebellar Prion Plaques and Prior History of Biopsy-Proven Primary Angiitis of the Central Nervous System: A Case for Iatrogenic Exposure?


Terry S. Singeltary

posted by Terry S. Singeltary Sr. at 12:52 PM

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