Tuesday, November 10, 2009

A retrospective immunohistochemical study reveals atypical scrapie has existed in the United Kingdom since at least 1987

Brief Research Reports

A retrospective immunohistochemical study reveals atypical scrapie has existed in the United Kingdom since at least 1987

Paul R. Webb1, Linda Powell, Margaret Denyer, Sarah Marsh, Colin Weaver, Marion M. Simmons, Elizabeth Johns, John Sheehan, Peter Horsfield, Chris Lyth, Christina Wilson, Ann Long, Saira Cawthraw, Ginny C. Saunders and Yvonne I. Spencer Correspondence: 1Corresponding Author: Paul R. Webb, Department of Pathology, Veterinary Laboratories Agency–Weybridge, Woodham Lane, New Haw, Addlestone, Surrey KT15 3NB, United Kingdom. p.webb@vla.defra.gsi.gov.uk

Atypical scrapie is a relatively recent discovery, and it was unknown whether it was a new phenomenon or whether it had existed undetected in the United Kingdom national flock. Before 1998, the routine statutory diagnosis of transmissible spongiform encephalopathy (TSE) in sheep relied on the presence of TSE vacuolation in the brainstem. This method would not have been effective for the detection of atypical scrapie. Currently, immunohistochemistry (IHC) and Western blot are commonly used for the differential diagnosis of classical and atypical scrapie. The IHC pattern of PrPd deposition in atypical scrapie is very different from that in classical scrapie using the same antibody. It is thus possible that because of a lack of suitable diagnostic techniques and awareness of this form of the disease, historic cases of atypical scrapie remain undiagnosed. Immunohistochemistry was performed on selected formalin-fixed, paraffin-embedded (FFPE) blocks of ovine brain from the Veterinary Laboratories Agency archives that were submitted for various reasons, including suspect neurological disorders, between 1980 and 1989. It was found that PrPd deposits in a single case were consistent with atypical scrapie. A method was developed to obtain a PrP genotype from FFPE tissues and was applied to material from this single case, which was shown to be AHQ/AHQ. This animal was a scrapie suspect from 1987, but diagnosis was not confirmed by the available techniques at that time.

Key Words: Atypical scrapie • prion • scrapie • transmissible spongiform encephalopathy • United Kingdom

http://jvdi.org/cgi/content/abstract/21/6/826?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=prion&searchid=1&FIRSTINDEX=0&volume=21&issue=6&resourcetype=HWCIT



Wednesday, August 20, 2008

Bovine Spongiform Encephalopathy Mad Cow Disease typical and atypical strains, was there a cover-up ? August 20, 2008

snip...

another question, just how long have these atypical BSE TSEs been around in the bovine ???

let's look at another case of atypical BSE in Germany way back in 1992 ;

Subject: atypical BSE reported in 1992 and conviently slaughterd and incinerated and then swept under rug for about 12 years Date: April 26, 2007 at 1:08 pm PST 1992

NEW BRAIN DISORDER

3. WHAT ABOUT REPORTS OF NEW FORM OF BSE?

THE VETERINARY RECORD HAS PUBLISHED AN ARTICLE ON A NEW BRAIN DISORDER OF CATTLE DISCOVERED THROUGH OUR CONTROL MEASURES FOR BSE. ALTHOUGH IT PRESENTS SIMILAR CLINICAL SIGNS TO BSE THERE ARE MAJOR DIFFERENCES IN THE HISTOPATHOLOGY AND INCUBATION PERIODS BETWEEN THE TWO. MUST EMPHASISE THAT THIS IS NOT BSE.

4. IS THIS NEW BRAIN DISORDER A THREAT?

WE DO NOT EVEN KNOW WHETHER THE AGENT OF THIS DISEASE IS TRANSMISSIBLE. IN ANY CASE, CASES SO FAR IDENTIFIED HAD SHOWN SIMILAR SYMPTOMS TO THOSE OF BSE, AND THEREFORE HAVE BEEN SLAUGHTERED AND INCINERATED, SO THAT IF A TRANSMISSIBLE AGENT WERE INVOLVED IT WOULD HAVE BEEN ELIMINATED. .......

http://web.archive.org/web/20030714222309/www.bseinquiry.gov.uk/files/yb/1992/10/26001001.pdf



2. The Collinge/Will dispute appears to rumble on. Dr. Collinge had told Dr. Tyrrell that Dr. Will's response to his criticism about sharing material had been ''quite unacceptable'' (in spite of it's apparently conciliatory tone). Apparently Professor Allen was now going to try and arrange a meeting to resolve the dispute. No action here for MAFF, although Mr. Murray may be interested.

3. Dr. Tyrrell regretted that the Committee had not seen the article on BBD. However he felt that for the time being NO specific action was called for. The most important need was to consider the possibility that the condition might be transmissible. As we have discussed, I suggested that we might circulate a paper to the members of the committee giving our appreciation of this condition (and perhaps of other non-BSE neurological conditions that had been identified in negative cases) and of any necessary follow up action. IF any Committee member felt strongly about this, or if the issue CAME TO A HEAD, we would call an interim meeting. He was happy with this approach. I would be grateful if Mr. Maslin could, in discussion with CVL and veterinary colleagues draft such a note, which will presumably very largely follow what Mr. Bradley's briefing paper has already said, taking account of DOH comments, We can then clear a final version with DOH before circulating it to Committee members.

http://web.archive.org/web/20030714222309/www.bseinquiry.gov.uk/files/yb/1992/10/29005001.pdf



IN CONFIDENCE

This is a highly competitive field and it really will be a pity if we allow many of the key findings to be published by overseas groups while we are unable to pursue our research findings because of this disagreement, which I hope we can make every effort to solve.

http://web.archive.org/web/20030714222309/www.bseinquiry.gov.uk/files/yb/1992/10/26002001.pdf



COLLINGE THREATENS TO GO TO MEDIA

http://web.archive.org/web/20030714222309/www.bseinquiry.gov.uk/files/yb/1992/12/16005001.pdf



2. The discovery might indicate the existence of a different strain of BSE from that present in the general epidemic or an unusual response by an individual host.

3. If further atypical lesion distribution cases are revealed in this herd then implications of misdiagnosis of 'negative' cases in other herds may not be insignificant.

snip...

This minute is re-issued with a wider distribution. The information contained herein should NOT be disseminated further except on the basis of ''NEED TO KNOW''.

R Bradley

http://web.archive.org/web/20010305223440/www.bseinquiry.gov.uk/files/yb/1993/02/17001001.pdf



IN CONFIDENCE

BSE ATYPICAL LESION DISTRIBUTION

http://web.archive.org/web/20010305223440/www.bseinquiry.gov.uk/files/yb/1993/03/14001001.pdf



snip...

Visit to USA ... info on BSE and Scrapie

http://web.archive.org/web/20010305222847/www.bseinquiry.gov.uk/files/yb/1988/10/00001001.pdf



HOUND STUDY

AS implied in the Inset 25 we must not _ASSUME_ that transmission of BSE to other species will invariably present pathology typical of a scrapie-like disease.

snip...

http://web.archive.org/web/20010305222642/www.bseinquiry.gov.uk/files/yb/1991/01/04004001.pdf



2005 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 42 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://web.archive.org/web/20010305223122/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

IN CONFIDENCE

CONCEPT NOT FOR FURTHER STUDY OF MATERIAL OBTAINED IN A SURVEY OF HOUNDS FOR EVIDENCE OF A SCRAPIE-LIKE SPONGIFORM ENCEPHALOPATHY (SE)

snip...

b) Fibrillar material closely similar to SAF, found in BSE/Scrapie, was observed in 19 (4.3%) cases, all of which were hounds > 7 years of age. 14/19 of these suspected SAF results correlated with cases in the unresolveable histopathological category.

snip...

The following proposals address the hypothesis that the hound survey observations represent a PrP related or scrapie-like disease of dogs in which the pathological response, and possible the spread of infectivity, is neuroanatomically localized. By inference this could also mean that the disorder is clinically silent and non-progressive.

http://web.archive.org/web/20010305223122/www.bseinquiry.gov.uk/files/yb/1995/02/09001001.pdf



Wednesday, August 20, 2008

Bovine Spongiform Encephalopathy Mad Cow Disease typical and atypical strains, was there a cover-up ? August 20, 2008



see full text ;

http://bse-atypical.blogspot.com/2008/08/bovine-spongiform-encephalopathy-mad.html



Monday, October 26, 2009

Similarities between Forms of Sheep Scrapie and Creutzfeldt-Jakob Disease Are Encoded by Distinct Prion Types

Published online before print October 22, 2009

http://nor-98.blogspot.com/2009/10/similarities-between-forms-of-sheep.html



Published online before print October 22, 2009 This Article

Articles by Wemheuer, W. M. Articles by Schulz-Schaeffer, W. J.

PubMed

PubMed Citation Articles by Wemheuer, W. M. Articles by Schulz-Schaeffer, W. J.

Copyright © 2009 American Society for Investigative Pathology American Journal of Pathology, doi:10.2353/ajpath.2009.090623

Accepted for publication August 19, 2009.

--------------------------------------------------------------------------------

Article

Similarities between Forms of Sheep Scrapie and Creutzfeldt-Jakob Disease Are Encoded by Distinct Prion Types

Wiebke M. Wemheuer*, Sylvie L. Benestad, Arne Wrede*, Ulf Schulze-Sturm*, Wilhelm E. Wemheuer, Uwe Hahmann*, Joanna Gawinecka, Ekkehard Schütz, Inga Zerr, Bertram Brenig, Bjørn Bratberg, Olivier Andréoletti¶, and Walter J. Schulz-Schaeffer*@ From the Prion and Dementia Research Unit,* Department of Neuropathology, University Medical Center Goettingen, Goettingen, Germany; National Veterinary Institute, Department of Pathology, Oslo, Norway; Institute of Veterinary Medicine, Faculty for Agricultural Sciences, University of Goettingen, Goettingen, Germany; National Transmissible Spongiform Encephalopathies Reference Center, Department of Neurology, University Medical Center Goettingen, Goettingen, Germany; and Animal Health,¶ Ecole Nationale Vétérinaire de Toulouse, Toulouse, France

@ To whom correspondence should be addressed. E-mail: wjschulz@med.uni-goettingen.de.

Abstract

Transmissible spongiform encephalopathies such as scrapie in sheep, Creutzfeldt-Jakob disease (CJD) in humans, and bovine sporadic encephalopathy in cattle are characterized by the accumulation of a misfolded protein: the pathological prion protein. Ever since bovine sporadic encephalopathy was discovered as the likely cause of the new variant of CJD in humans, parallels between human and animal transmissible spongiform encephalopathies must be viewed under the aspect of a disease risk for humans. In our study we have compared prion characteristics of different forms of sheep scrapie with those of different phenotypes of sporadic CJD. The disease characteristics of sporadic CJD depend considerably on the prion type 1 or 2. Our results show that there are obvious parallels between sporadic CJD type 1 and the so-called atypical/Nor98 scrapie. These parelleles apply to the deposition form of pathological prion protein in the brain, detected by the paraffin-embedded-tissue blot and the prion aggregate stability with regard to denaturation by the chaotropic salt guanidine hydrochloride. The same applies to sporadic CJD type 2 and classical scrapie. The observed parallels between types of sporadic CJD and types of sheep scrapie demonstrate that distinct groups of prion disease exist in different species. This should be taken into consideration when discussing interspecies transmission.

http://ajp.amjpathol.org/cgi/content/abstract/ajpath.2009.090623v1



P.4.25

Human susceptibility to atypical scrapie

Chris Plinston, Rona Barron, Nora Hunter The Roslin Institute and R(D)SVS, University of Edinburgh, UK

Background: Isolates of classical sheep scrapie are thought to pose little risk to humans as there have been no documented links between presence of sheep scrapie and the development of human TSE disease. However, the link between BSE and the development of vCJD in humans proves that a risk does exist from ruminant TSE disease, and therefore all new ruminant TSEs may potentially be transmissible to humans. Due to increased sensitivity of TSE diagnostic assay systems, a new TSE of sheep termed 'atypical scrapie' has been identified. This disease has been difficult to identify, and is found mainly in sheep which are previously thought to have a genetic makeup that made them resistant to scrapie. It is unclear whether this is a new TSE of sheep, an old disease which has only been identified through increased surveillance, or if it represents the phenotype of classical scrapie in so called 'resistant' sheep PrP genotypes.

Objectives: The objective of the study is to assess relative transmissibility of atypical scrapie isolates to humans and the associated risk to the population.

Methods: In order to determine whether atypical scrapie poses a risk to human health we have transmitted isolates from three different sheep PrP genotypes to our gene targeted transgenic mice which express human PrP with the M129V polymorphism known to be important in human susceptibility to disease. Mice of all three PrP genotypes have been inoculated intracerebrally with atypical scrapie isolates.

Discussion: In order to prevent the emergence of a new human TSE, we need to be able to assess the risk to humans from new emerging TSEs in livestock. The study of atypical scrapie infection in these transgenic lines could therefore provide important information on the host range and disease characteristics associated with such isolates. Preventative measures could then be put in place before this disease gives rise to another human disease variant and an underlying level of infection in the population.

P.5.21

Parallels between different forms of sheep scrapie and types of Creutzfeldt-Jakob disease (CJD)

Wiebke M. Wemheuer1, Sylvie L. Benestad2, Arne Wrede1, Wilhelm E. Wemheuer3, Tatjana Pfander1, Bjørn Bratberg2, Bertram Brenig3,Walter J. Schulz-Schaeffer1 1University Medical Center Goettingen, Germany; 2Institute of Veterinary Medicine Oslo, Norway; 3Institute of Veterinary Medicine Goettingen, Germany

Background: Scrapie in sheep and goats is often regarded as the archetype of prion diseases. In 1998, a new form of scrapie - atypical/Nor98 scrapie - was described that differed from classical scrapie in terms of epidemiology, Western blot profile, the distribution of pathological prion protein (PrPSc) in the body and its stability against proteinase K. In a similar way, distinct disease types exist in sporadic Creutzfeldt-Jakob disease (CJD). They differ with regard to their clinical outcome, Western blot profile and PrPSc deposition pattern in the central nervous system (CNS).

Objectives: The comparison of PrPSc deposits in sheep scrapie and human sporadic CJD. Methods: Tissues of the CNS of sheep with classical scrapie, sheep with atypical/Nor98 scrapie and 20 patients with sporadic CJD were examined using the sensitive Paraffin Embedded Tissue (PET) blot method. The results were compared with those obtained by immunohistochemistry. With the objective of gaining information on the protein conformation, the PrPSc of classical and atypical/Nor98 sheep scrapie and sporadic CJD was tested for its stability against denaturation with guanidine hydrochloride (GdnHCl) using a Membrane Adsorption Assay.

Results: The PrPSc of atypical/Nor98 scrapie cases and of CJD prion type 1 patients exhibits a mainly reticular/synaptic deposition pattern in the brain and is relatively sensitive to denaturation with GdnHCl. In contrast classical scrapie cases and CJD prion type 2 patients have a more complex PrPSc deposition pattern in common that consists of larger PrPSc aggregates and the PrPSc itself is comparatively stable against denaturation.

Discussion: The similarity between CJD types and scrapie types indicates that at least two comparable forms of the misfolded prion protein exist beyond species barriers and can elicit prion diseases. It seems therefore reasonable to classify classical and atypical/Nor98 scrapie - in analogy to the existing CJD types - as different scrapie types.

http://www.prion2009.com/sites/default/files/Prion2009_Book_of_Abstracts.pdf



Wednesday, July 1, 2009

Nor98 scrapie identified in the United States J Vet Diagn Invest 21:454-463 (2009)

http://nor-98.blogspot.com/2009/07/nor98-scrapie-identified-in-united.html



P03.141

Aspects of the Cerebellar Neuropathology in Nor98

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

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

***The pathology features of Nor98 in the cerebellum of the affected sheep showed similarities with those of sporadic Creutzfeldt-Jakob disease in humans.

http://www.prion2007.com/pdf/Prion%20Book%20of%20Abstracts.pdf



PR-26

NOR98 SHOWS MOLECULAR FEATURES REMINISCENT OF GSS

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

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

*** Intriguingly, these conclusions suggest that some pathological features of Nor98 are reminiscent of Gerstmann-Sträussler-Scheinker disease.

119

http://www.neuroprion.com/pdf_docs/conferences/prion2006/abstract_book.pdf



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

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

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

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

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

http://www.pnas.org/content/102/44/16031.abstract



Monday, December 1, 2008

When Atypical Scrapie cross species barriers

Authors

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

Content

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

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

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

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

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

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

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

http://www.neuroprion.org/resources/pdf_docs/conferences/prion2008/abstract-book-prion2008.pdf



NOR-98 ATYPICAL SCRAPIE 5 cases documented in USA in 5 different states USA 2007

http://nor-98.blogspot.com/2008/04/seac-spongiform-encephalopathy-advisory.html



Tuesday, June 3, 2008 SCRAPIE USA UPDATE JUNE 2008 NOR-98 REPORTED PA

http://nor-98.blogspot.com/2008/06/scrapie-usa-update-june-2008-nor-98.html



Monday, September 1, 2008

RE-FOIA OF DECLARATION OF EXTRAORDINARY EMERGENCY BECAUSE OF AN ATYPICAL T.S.E. (PRION DISEASE) OF FOREIGN ORIGIN IN THE UNITED STATES [No. 00-072-1] September 1, 2008

http://foiamadsheepmadrivervalley.blogspot.com/2008/09/re-foia-of-declaration-of-extraordinary.html



http://nor-98.blogspot.com/



http://scrapie-usa.blogspot.com/



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.

PMID: 6997404

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



12/10/76 AGRICULTURAL RESEARCH COUNCIL REPORT OF THE ADVISORY COMMITTE ON SCRAPIE Office Note CHAIRMAN: PROFESSOR PETER WILDY

snip...

A The Present Position with respect to Scrapie

A1 The Problem

Scrapie is a natural disease of sheep and goats. It is a slow and inexorably progressive degenerative disorder of the nervous system and it ia fatal. It is enzootic in the United Kingdom but not in all countries.

The field problem has been reviewed by a MAFF working group (ARC 35/77). It is difficult to assess the incidence in Britain for a variety of reasons but the disease causes serious financial loss; it is estimated that it cost Swaledale breeders alone $l.7 M during the five years 1971-1975. A further inestimable loss arises from the closure of certain export markets, in particular those of the United States, to British sheep.

It is clear that scrapie in sheep is important commercially and for that reason alone effective measures to control it should be devised as quickly as possible.

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

Epidemiology of Scrapie in the United States 1977


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





http://www.bseinquiry.gov.uk/files/mb/m08b/tab64.pdf




http://scrapie-usa.blogspot.com/





Like lambs to the slaughter 31 March 2001 by Debora MacKenzie Magazine issue 2284

FOUR years ago, Terry Singeltary watched his mother die horribly from a degenerative brain disease. Doctors told him it was Alzheimer's, but Singeltary was suspicious. The diagnosis didn't fit her violent symptoms, and he demanded an autopsy. It showed she had died of sporadic Creutzfeldt-Jakob disease.

Most doctors believe that sCJD is caused by a prion protein deforming by chance into a killer. But Singeltary thinks otherwise. He is one of a number of campaigners who say that some sCJD, like the variant CJD related to BSE, is caused by eating meat from infected animals. Their suspicions have focused on sheep carrying scrapie, a BSE-like disease that is widespread in flocks across Europe and North America.

Now scientists in France have stumbled across new evidence that adds weight to the campaigners' fears. To their complete surprise, the researchers found that one strain of scrapie causes the same brain damage in ...

http://www.newscientist.com/article/mg16922840.300-like-lambs-to-the-slaughter.html



http://nor-98.blogspot.com/



http://scrapie-usa.blogspot.com/



also see ;

Monday, October 19, 2009

Atypical BSE, BSE, and other human and animal TSE in North America Update October 19, 2009

http://bse-atypical.blogspot.com/2009/10/atypical-bse-bse-and-other-human-and.html



Thursday, November 05, 2009

Incidence and spectrum of sporadic Creutzfeldt-Jakob disease variants with mixed phenotype and co-occurrence of PrPSc types: an updated classification

http://creutzfeldt-jakob-disease.blogspot.com/2009/11/incidence-and-spectrum-of-sporadic.html



WHO WILL WATCH THE CHILDREN for CJD over the next 5 decades ?

FOR 4 years, the USDA fed dead stock downer cows, the most high risk cattle for mad cow disease and other dangerous pathogens to children all across the USA via the USDA certified dead stock downer cow school lunch program...

SCHOOL LUNCH PROGRAM FROM DOWNER CATTLE UPDATE

http://downercattle.blogspot.com/2009/05/who-will-watch-children.html



http://downercattle.blogspot.com/



Monday, October 19, 2009

Atypical BSE, BSE, and other human and animal TSE in North America Update October 19, 2009

http://bse-atypical.blogspot.com/2009/10/atypical-bse-bse-and-other-human-and.html



Sunday, September 6, 2009

MAD COW USA 1997 SECRET VIDEO

http://madcowusda.blogspot.com/2009/09/mad-cow-usa-1997-video.html



U.S.A. HIDING MAD COW DISEASE VICTIMS AS SPORADIC CJD ? see video at bottom

http://creutzfeldt-jakob-disease.blogspot.com/2009/07/usa-hiding-mad-cow-disease-victims-as.html



DAMNING TESTIMONY FROM STANLEY PRUSINER THE NOBEL PEACE PRIZE WINNER ON PRIONS SPEAKING ABOUT ANN VENEMAN see video

http://maddeer.org/video/embedded/prusinerclip.html



CVM Annual Report Fiscal Year 2008: October 1, 2007-September 30, 2008

PUTTING LIPSTICK ON A PIG AND TAKING HER TO A DANCE...TSS

BSE Feed Rule Enforcement: A Decade of Success OFF TO A FAST START

http://madcowfeed.blogspot.com/2008/06/texas-firm-recalls-cattle-heads-that.html



2009 UPDATE ON ALABAMA AND TEXAS MAD COWS 2005 and 2006

http://bse-atypical.blogspot.com/2006/08/bse-atypical-texas-and-alabama-update.html



Monday, October 26, 2009

MAD COW DISEASE, AND U.S. BEEF TRADE

MAD COW DISEASE, CJD, TSE, SOUND SCIENCE, COMMERCE, AND SELLING YOUR SOUL TO THE DEVIL

http://usdameatexport.blogspot.com/2009/10/mad-cow-disease-and-us-beef-trade.html



Sent: Tuesday, November 03, 2009 5:14 PM Subject: Re: FOIA REQUEST ON FEED RECALL PRODUCT Bulk Whole Barley, Recall # V-256-2009 DISTRIBUTION TX END OF ENFORCEMENT REPORT FOR AUGUST 26, 2009

http://madcowfeed.blogspot.com/2009/11/re-foia-request-on-feed-recall-product.html



BSE (Mad Cow) Update: Do Reports of sCJD Clusters Matter?

snip... see full text ;

http://cjdtexas.blogspot.com/



Thursday, November 05, 2009

Incidence and spectrum of sporadic Creutzfeldt-Jakob disease variants with mixed phenotype and co-occurrence of PrPSc types: an updated classification

http://creutzfeldt-jakob-disease.blogspot.com/2009/11/incidence-and-spectrum-of-sporadic.html



Friday, October 23, 2009

Creutzfeldt-Jakob Disease Surveillance Texas Data for Reporting Years 2000-2008

http://cjdtexas.blogspot.com/2009/10/creutzfeldt-jakob-disease-surveillance.html



Thursday, November 05, 2009

Incidence and spectrum of sporadic Creutzfeldt-Jakob disease variants with mixed phenotype and co-occurrence of PrPSc types: an updated classification

http://creutzfeldt-jakob-disease.blogspot.com/2009/11/incidence-and-spectrum-of-sporadic.html



Terry S. Singeltary Sr. P.O. Box 42 Bacliff, Texas USA 77518

Monday, October 26, 2009

Similarities between Forms of Sheep Scrapie and Creutzfeldt-Jakob Disease Are Encoded by Distinct Prion Types

Published online before print October 22, 2009 This Article

Articles by Wemheuer, W. M. Articles by Schulz-Schaeffer, W. J.

PubMed

PubMed Citation Articles by Wemheuer, W. M. Articles by Schulz-Schaeffer, W. J.

Copyright © 2009 American Society for Investigative Pathology American Journal of Pathology, doi:10.2353/ajpath.2009.090623

Accepted for publication August 19, 2009.

--------------------------------------------------------------------------------

Article

Similarities between Forms of Sheep Scrapie and Creutzfeldt-Jakob Disease Are Encoded by Distinct Prion Types

Wiebke M. Wemheuer*, Sylvie L. Benestad, Arne Wrede*, Ulf Schulze-Sturm*, Wilhelm E. Wemheuer, Uwe Hahmann*, Joanna Gawinecka, Ekkehard Schütz, Inga Zerr, Bertram Brenig, Bjørn Bratberg, Olivier Andréoletti¶, and Walter J. Schulz-Schaeffer*@ From the Prion and Dementia Research Unit,* Department of Neuropathology, University Medical Center Goettingen, Goettingen, Germany; National Veterinary Institute, Department of Pathology, Oslo, Norway; Institute of Veterinary Medicine, Faculty for Agricultural Sciences, University of Goettingen, Goettingen, Germany; National Transmissible Spongiform Encephalopathies Reference Center, Department of Neurology, University Medical Center Goettingen, Goettingen, Germany; and Animal Health,¶ Ecole Nationale Vétérinaire de Toulouse, Toulouse, France

@ To whom correspondence should be addressed. E-mail: wjschulz@med.uni-goettingen.de.

Abstract

Transmissible spongiform encephalopathies such as scrapie in sheep, Creutzfeldt-Jakob disease (CJD) in humans, and bovine sporadic encephalopathy in cattle are characterized by the accumulation of a misfolded protein: the pathological prion protein. Ever since bovine sporadic encephalopathy was discovered as the likely cause of the new variant of CJD in humans, parallels between human and animal transmissible spongiform encephalopathies must be viewed under the aspect of a disease risk for humans. In our study we have compared prion characteristics of different forms of sheep scrapie with those of different phenotypes of sporadic CJD. The disease characteristics of sporadic CJD depend considerably on the prion type 1 or 2. Our results show that there are obvious parallels between sporadic CJD type 1 and the so-called atypical/Nor98 scrapie. These parelleles apply to the deposition form of pathological prion protein in the brain, detected by the paraffin-embedded-tissue blot and the prion aggregate stability with regard to denaturation by the chaotropic salt guanidine hydrochloride. The same applies to sporadic CJD type 2 and classical scrapie. The observed parallels between types of sporadic CJD and types of sheep scrapie demonstrate that distinct groups of prion disease exist in different species. This should be taken into consideration when discussing interspecies transmission.

http://ajp.amjpathol.org/cgi/content/abstract/ajpath.2009.090623v1


P.4.25

Human susceptibility to atypical scrapie

Chris Plinston, Rona Barron, Nora Hunter The Roslin Institute and R(D)SVS, University of Edinburgh, UK

Background: Isolates of classical sheep scrapie are thought to pose little risk to humans as there have been no documented links between presence of sheep scrapie and the development of human TSE disease. However, the link between BSE and the development of vCJD in humans proves that a risk does exist from ruminant TSE disease, and therefore all new ruminant TSEs may potentially be transmissible to humans. Due to increased sensitivity of TSE diagnostic assay systems, a new TSE of sheep termed 'atypical scrapie' has been identified. This disease has been difficult to identify, and is found mainly in sheep which are previously thought to have a genetic makeup that made them resistant to scrapie. It is unclear whether this is a new TSE of sheep, an old disease which has only been identified through increased surveillance, or if it represents the phenotype of classical scrapie in so called 'resistant' sheep PrP genotypes.

Objectives: The objective of the study is to assess relative transmissibility of atypical scrapie isolates to humans and the associated risk to the population.

Methods: In order to determine whether atypical scrapie poses a risk to human health we have transmitted isolates from three different sheep PrP genotypes to our gene targeted transgenic mice which express human PrP with the M129V polymorphism known to be important in human susceptibility to disease. Mice of all three PrP genotypes have been inoculated intracerebrally with atypical scrapie isolates.

Discussion: In order to prevent the emergence of a new human TSE, we need to be able to assess the risk to humans from new emerging TSEs in livestock. The study of atypical scrapie infection in these transgenic lines could therefore provide important information on the host range and disease characteristics associated with such isolates. Preventative measures could then be put in place before this disease gives rise to another human disease variant and an underlying level of infection in the population.

P.5.21

Parallels between different forms of sheep scrapie and types of Creutzfeldt-Jakob disease (CJD)

Wiebke M. Wemheuer1, Sylvie L. Benestad2, Arne Wrede1, Wilhelm E. Wemheuer3, Tatjana Pfander1, Bjørn Bratberg2, Bertram Brenig3,Walter J. Schulz-Schaeffer1 1University Medical Center Goettingen, Germany; 2Institute of Veterinary Medicine Oslo, Norway; 3Institute of Veterinary Medicine Goettingen, Germany

Background: Scrapie in sheep and goats is often regarded as the archetype of prion diseases. In 1998, a new form of scrapie - atypical/Nor98 scrapie - was described that differed from classical scrapie in terms of epidemiology, Western blot profile, the distribution of pathological prion protein (PrPSc) in the body and its stability against proteinase K. In a similar way, distinct disease types exist in sporadic Creutzfeldt-Jakob disease (CJD). They differ with regard to their clinical outcome, Western blot profile and PrPSc deposition pattern in the central nervous system (CNS).

Objectives: The comparison of PrPSc deposits in sheep scrapie and human sporadic CJD. Methods: Tissues of the CNS of sheep with classical scrapie, sheep with atypical/Nor98 scrapie and 20 patients with sporadic CJD were examined using the sensitive Paraffin Embedded Tissue (PET) blot method. The results were compared with those obtained by immunohistochemistry. With the objective of gaining information on the protein conformation, the PrPSc of classical and atypical/Nor98 sheep scrapie and sporadic CJD was tested for its stability against denaturation with guanidine hydrochloride (GdnHCl) using a Membrane Adsorption Assay.

Results: The PrPSc of atypical/Nor98 scrapie cases and of CJD prion type 1 patients exhibits a mainly reticular/synaptic deposition pattern in the brain and is relatively sensitive to denaturation with GdnHCl. In contrast classical scrapie cases and CJD prion type 2 patients have a more complex PrPSc deposition pattern in common that consists of larger PrPSc aggregates and the PrPSc itself is comparatively stable against denaturation.

Discussion: The similarity between CJD types and scrapie types indicates that at least two comparable forms of the misfolded prion protein exist beyond species barriers and can elicit prion diseases. It seems therefore reasonable to classify classical and atypical/Nor98 scrapie - in analogy to the existing CJD types - as different scrapie types.

http://www.prion2009.com/sites/default/files/Prion2009_Book_of_Abstracts.pdf


Wednesday, July 1, 2009

Nor98 scrapie identified in the United States J Vet Diagn Invest 21:454-463 (2009)

http://nor-98.blogspot.com/2009/07/nor98-scrapie-identified-in-united.html


P03.141

Aspects of the Cerebellar Neuropathology in Nor98

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

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

***The pathology features of Nor98 in the cerebellum of the affected sheep showed similarities with those of sporadic Creutzfeldt-Jakob disease in humans.

http://www.prion2007.com/pdf/Prion%20Book%20of%20Abstracts.pdf


PR-26

NOR98 SHOWS MOLECULAR FEATURES REMINISCENT OF GSS

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

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

*** Intriguingly, these conclusions suggest that some pathological features of Nor98 are reminiscent of Gerstmann-Sträussler-Scheinker disease.

119

http://www.neuroprion.com/pdf_docs/conferences/prion2006/abstract_book.pdf


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

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

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

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

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

http://www.pnas.org/content/102/44/16031.abstract


Monday, December 1, 2008

When Atypical Scrapie cross species barriers

Authors

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

Content

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

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

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

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

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

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

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

http://www.neuroprion.org/resources/pdf_docs/conferences/prion2008/abstract-book-prion2008.pdf


NOR-98 ATYPICAL SCRAPIE 5 cases documented in USA in 5 different states USA 2007

http://nor-98.blogspot.com/2008/04/seac-spongiform-encephalopathy-advisory.html


Tuesday, June 3, 2008 SCRAPIE USA UPDATE JUNE 2008 NOR-98 REPORTED PA

http://nor-98.blogspot.com/2008/06/scrapie-usa-update-june-2008-nor-98.html


Monday, September 1, 2008

RE-FOIA OF DECLARATION OF EXTRAORDINARY EMERGENCY BECAUSE OF AN ATYPICAL T.S.E. (PRION DISEASE) OF FOREIGN ORIGIN IN THE UNITED STATES [No. 00-072-1] September 1, 2008

http://foiamadsheepmadrivervalley.blogspot.com/2008/09/re-foia-of-declaration-of-extraordinary.html


http://nor-98.blogspot.com/


http://scrapie-usa.blogspot.com/


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.

PMID: 6997404

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


12/10/76 AGRICULTURAL RESEARCH COUNCIL REPORT OF THE ADVISORY COMMITTE ON SCRAPIE Office Note CHAIRMAN: PROFESSOR PETER WILDY

snip...

A The Present Position with respect to Scrapie

A1 The Problem

Scrapie is a natural disease of sheep and goats. It is a slow and inexorably progressive degenerative disorder of the nervous system and it ia fatal. It is enzootic in the United Kingdom but not in all countries.

The field problem has been reviewed by a MAFF working group (ARC 35/77). It is difficult to assess the incidence in Britain for a variety of reasons but the disease causes serious financial loss; it is estimated that it cost Swaledale breeders alone $l.7 M during the five years 1971-1975. A further inestimable loss arises from the closure of certain export markets, in particular those of the United States, to British sheep.

It is clear that scrapie in sheep is important commercially and for that reason alone effective measures to control it should be devised as quickly as possible.

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

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

snip...

76/10.12/4.6

http://www.bseinquiry.gov.uk/files/yb/1976/10/12004001.pdf


Epidemiology of Scrapie in the United States 1977

http://www.bseinquiry.gov.uk/files/mb/m08b/tab64.pdf


http://scrapie-usa.blogspot.com/


Like lambs to the slaughter 31 March 2001 by Debora MacKenzie Magazine issue 2284

FOUR years ago, Terry Singeltary watched his mother die horribly from a degenerative brain disease. Doctors told him it was Alzheimer's, but Singeltary was suspicious. The diagnosis didn't fit her violent symptoms, and he demanded an autopsy. It showed she had died of sporadic Creutzfeldt-Jakob disease.

Most doctors believe that sCJD is caused by a prion protein deforming by chance into a killer. But Singeltary thinks otherwise. He is one of a number of campaigners who say that some sCJD, like the variant CJD related to BSE, is caused by eating meat from infected animals. Their suspicions have focused on sheep carrying scrapie, a BSE-like disease that is widespread in flocks across Europe and North America.

Now scientists in France have stumbled across new evidence that adds weight to the campaigners' fears. To their complete surprise, the researchers found that one strain of scrapie causes the same brain damage in ...

http://www.newscientist.com/article/mg16922840.300-like-lambs-to-the-slaughter.html


http://nor-98.blogspot.com/


http://scrapie-usa.blogspot.com/


Monday, October 19, 2009

Atypical BSE, BSE, and other human and animal TSE in North America Update October 19, 2009

http://bse-atypical.blogspot.com/2009/10/atypical-bse-bse-and-other-human-and.html


Terry S. Singeltary Sr.

P.O. Box 42

Bacliff, Texas USA 77518

Wednesday, July 8, 2009

Transgenic Mice Expressing Porcine Prion Protein Resistant to Classical Scrapie but Susceptible to Sheep BSE and Atypical Scrapie

DOI: 10.3201/eid1508.081218

Suggested citation for this article: Espinosa J-C, Herva M-E, Andréoletti O, Padilla D, Lacroux C, Cassard H, et al. Transgenic mice expressing porcine prion protein resistant to classical scrapie but susceptible to sheep bovine spongiform encephalopathy and atypical scrapie. Emerg Infect Dis. 2009 Aug; [Epub ahead of print]

Transgenic Mice Expressing Porcine Prion Protein Resistant to Classical Scrapie but Susceptible to Sheep Bovine Spongiform Encephalopathy and Atypical Scrapie

Juan-Carlos Espinosa,1 María-Eugenia Herva,1 Olivier Andréoletti, Danielle Padilla, Caroline Lacroux, Hervé Cassard, Isabelle Lantier, Joaquin Castilla, and Juan-María Torres

Author affiliations: Centro de Investigación en Sanidad Animal, Madrid, Spain (J.-C. Espinosa, M.-E. Herva, D. Padilla, J. Castilla, J.-M. Torres); École Nationale Vétérinaire de Toulouse, Toulouse, France (O. Andréoletti, C. Lacroux, H. Cassard); and Centre Institut National de la Recherche Agronomique de Tours, Nouzilly, France (I. Lantier)

1These authors contributed equally to this article.

How susceptible pigs are to infection with sheep prions is unknown. We show, through transmission experiments in transgenic mice expressing porcine prion protein (PrP), that the susceptibility of this mouse model to bovine spongiform encephalopathy (BSE) can be enhanced after its passage in ARQ sheep, indicating that the pathogenicity of the BSE agent is modified after passage in sheep. Transgenic mice expressing porcine PrP were, nevertheless, completely resistant to infection with a broad panel of classical scrapie isolates from different sheep PrP genotypes and with different biochemical characteristics. The atypical (Nor98 like) isolate (SC-PS152) was the only scrapie isolate capable of transmission in these mice, although with a marked transmission barrier. Unexpectedly, the atypical scrapie agent appeared to undergo a strain phenotype shift upon transmission to porcine-PrP transgenic mice and acquired new strain properties, suggesting that atypical scrapie agent may exhibit different phenotypes depending on the host cellular PrP or other genetic factors.

snip...

Discussion

In this study, transgenic mice expressing porcine PrP (8) were used to assess the transmission capacity of a wide range of TSE agents from sheep. Our results indicated that none of the classical scrapie isolates tested was transmitted to our porcine PrP mouse model after intracerebral inoculation (Table), suggesting a highly (if not completely) resistance to the classical scrapie strains tested independently of their origin and biochemical signature. The absence of successful transmission of the SC-PS48 isolates with an unglycosylated bands of 19 kDa-like BSE suggests a BSE-unrelated origin for these BSE-like scrapie strains.

The atypical isolate SC-PS152 was the only scrapie isolate able to infect the Po-PrP mouse model after intracerebral inoculation (Table), albeit with a low efficiency of infection in the first passage (attack rate 16%). These results suggest the potential ability of atypical scrapie prions to infect pigs, although with a strong transmission barrier. Given the increasing number of atypical scrapie cases found in Europe and in North America, the potential ability of atypical scrapie to adapt to the pig becoming more easily transmitted could raise concerns about the potential danger of feeding ruminant meat and bone meal to swine.

In our transmission experiments, an obviously shorter survival period (458 ± 11 dpi) and an increased attack rate (100%) were observed in PoPrP-Tg001 mice inoculated with sheep BSE (Table) compared with those inoculated with the original cattle BSE (>650 dpi, 19%). These last figures correlate well with those reported for other cattle BSE isolates (Table). Differences in survival times were maintained after subsequent passages in this mouse model (Table), suggesting that the increased infectivity of sheep BSE cannot be linked to a higher infectious titer in the initial inoculum but must be the outcome of a modification in the pathogenicity of the agent. We can also rule out that the primary amino acid sequence of the ovine PrPSC leads to more efficient conversion of porcine PrPC because scrapie isolates from sheep with the same ARQ-PrP genotype were not able to infect these mice (Table). Taken together, the increased infectivity of sheep BSE in the porcine PrP mouse model must be considered as increased pathogenicity of the agent attributable to its passage in sheep. These features support previous results indicating that the BSE agent modifies its biological properties after passage in sheep, with the result that its pathogenicity increases in transgenic mice expressing bovine PrP (24). An increased pathogenicity of ovine BSE was also reported in conventional RIII mice when compared with retrospective cattle BSE experiments (36). In other prion strains, passage through an intermediate species has also been noted to alter host susceptibility (37).

The enhanced infectivity of the BSE agent after its passage in ARQ sheep raises concern about its potential danger for other species, including humans. This question, as well as others related to the infectivity of the new porcine prion generated in this study, is currently being addressed in transmission experiments using transgenic mice expressing human PrP.

Upon passages in porcine PrP transgenic mice, the BSE agent retained most of its biochemical properties, except for its PrPres glycoprofile in which some differences were appreciable. Our comparative analysis of cattle BSE and sheep BSE upon transmission in porcine PrP transgenic mice showed that both agents exhibit similar molecular (Figure 2) and neuropathologic properties (Figure 4). These features were preserved after subsequent passages. These results suggest that, despite their modified pathogenicity, the 2 porcine prions generated share the same biochemical and neuropathologic properties, regardless of whether the BSE agent used to inoculate the mice was obtained from ARQ sheep or cows. In agreement with these results, the increased infectivity of sheep BSE previously observed upon transmission in bovine PrP transgenic mice was not reflected in its molecular or neuropathologic properties (24).

The atypical scrapie (SC-PS152) agent appeared to undergo a strain phenotype shift upon transmission to porcine PrP transgenic mice. Surprisingly, this novel strain phenotype was similar to that of sheep BSE propagated in the same mice in terms of several features: 1) survival times observed after stabilization in PoPrP-Tg001 mice (second passages) were similar (Table); 2) PrPres molecular profiles of the 2 agents in porcine PrP mice were indistinguishable (Figure 3); and 3) vacuolation profiles observed in second passages largely overlapped (Figure 4).

These findings could reflect the evolutionary potential of prion agents upon transmission to a foreign host able to promote strain shift and emergence of new properties (38,39). The converging molecular, neuropathologic, and biological properties of atypical scrapie and sheep BSE upon propagation in porcine transgenic mice could be the consequence of a restriction imposed by the porcine PrPC, which might only admit a few options as it changes its conformation to PrPSC.

Our results could also suggest a common origin for sheep BSE and atypical scrapie agents, which may exhibit different phenotypes depending on the host PrPC or other host factors.

Although this last explanation seems to be less likely, so far we cannot draw any definitive conclusion on this issue. Whichever the case, the ability of an atypical scrapie to infect other species and its potential capacity to undergo a strain phenotype shift in the new host prompts new concerns about the possible spread of this uncommon TSE in other species as a masked prion undistinguishable from other strains.

snip... see full text ;



http://www.cdc.gov/eid/content/15/8/pdfs/08-1218.pdf



Saturday, May 2, 2009

APHIS AND WHO PLAN TO EXEMPT THE ATYPICAL SCRAPIE NOR-98 FROM REGULATIONS AT MEETING THIS MONTH



http://nor-98.blogspot.com/2009/05/aphis-and-who-plan-to-exempt-atypical.html



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.

PMID: 6997404



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



12/10/76 AGRICULTURAL RESEARCH COUNCIL REPORT OF THE ADVISORY COMMITTE ON SCRAPIE Office Note CHAIRMAN: PROFESSOR PETER WILDY

snip...

A The Present Position with respect to Scrapie

A1 The Problem

Scrapie is a natural disease of sheep and goats. It is a slow and inexorably progressive degenerative disorder of the nervous system and it ia fatal. It is enzootic in the United Kingdom but not in all countries.

The field problem has been reviewed by a MAFF working group (ARC 35/77). It is difficult to assess the incidence in Britain for a variety of reasons but the disease causes serious financial loss; it is estimated that it cost Swaledale breeders alone $l.7 M during the five years 1971-1975. A further inestimable loss arises from the closure of certain export markets, in particular those of the United States, to British sheep.

It is clear that scrapie in sheep is important commercially and for that reason alone effective measures to control it should be devised as quickly as possible.

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

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

snip...

76/10.12/4.6



http://www.bseinquiry.gov.uk/files/yb/1976/10/12004001.pdf



Epidemiology of Scrapie in the United States 1977



http://www.bseinquiry.gov.uk/files/mb/m08b/tab64.pdf



http://scrapie-usa.blogspot.com/



Like lambs to the slaughter 31 March 2001 by Debora MacKenzie Magazine issue 2284

FOUR years ago, Terry Singeltary watched his mother die horribly from a degenerative brain disease. Doctors told him it was Alzheimer's, but Singeltary was suspicious. The diagnosis didn't fit her violent symptoms, and he demanded an autopsy. It showed she had died of sporadic Creutzfeldt-Jakob disease.

Most doctors believe that sCJD is caused by a prion protein deforming by chance into a killer. But Singeltary thinks otherwise. He is one of a number of campaigners who say that some sCJD, like the variant CJD related to BSE, is caused by eating meat from infected animals. Their suspicions have focused on sheep carrying scrapie, a BSE-like disease that is widespread in flocks across Europe and North America.

Now scientists in France have stumbled across new evidence that adds weight to the campaigners' fears. To their complete surprise, the researchers found that one strain of scrapie causes the same brain damage in ...



http://www.newscientist.com/article/mg16922840.300-like-lambs-to-the-slaughter.html



http://nor-98.blogspot.com/



http://scrapie-usa.blogspot.com/



see full text ;

Wednesday, July 1, 2009

Nor98 scrapie identified in the United States J Vet Diagn Invest 21:454-463 (2009)



http://nor-98.blogspot.com/2009/07/nor98-scrapie-identified-in-united.html




4.296 On 20 August 1990, a positive result was recorded in the CVL's experiment to transmit BSE to pigs. One pig had been diagnosed by post-mortem pathology as having developed a spongiform encephalopathy. A confidential pathology report submitted by Mr Gerald Wells, Head of the CVL's Neuropathology Section, to his colleague Mr Michael Dawson in the Virology Department, included the following remark:

The result, albeit confined to one animal in the experimental challenge group is incontrovertible evidence of the transmissibility of BSE to the pig by simultaneous intracerebral, intravenous and intraperitoneal inoculation routes. 11



http://www.bseinquiry.gov.uk/report/volume11/chapter8.htm#808467



http://www.bseinquiry.gov.uk/report/volume11/chapter8.htm#808471



http://www.bseinquiry.gov.uk/report/volume11/chapter8.htm#808475



http://www.bseinquiry.gov.uk/report/volume11/chapter8.htm#808479



http://www.bseinquiry.gov.uk/report/volume11/chapter8.htm#808483



http://www.bseinquiry.gov.uk/report/volume11/chapter8.htm#808487



4.303 The minutes of the meeting record that:

It was very difficult to draw conclusions from one experimental result for what may happen in the field. However it would be prudent to exclude specified bovine offals from the pig diet. Although any relationship between BSE and the finding of a spongiform encephalopathy in cats had yet to be demonstrated, the fact that this had occurred suggested that a cautious view should be taken of those species which might be susceptible. The 'specified offals' of bovines should therefore be excluded from the feed of all species. 17



http://www.bseinquiry.gov.uk/report/volume11/chapter8.htm#808491



4.308 SEAC issued formal advice on 20 September 1990, following its meeting on the previous day. The advice stated:

Since this result shows that pigs can get spongiform encephalopathy, even though there is no evidence that they have done so in the field, we believe that pigs should no longer be fed with protein derived from bovine tissues which might contain the BSE agent, ie, those 'specified' bovine offals that are already excluded from human consumption. It would make sense to extend this prohibition to feed for all species, including household pets, as other species have now developed spongiform encephalopathies. We are aware that many animal feed compounders and pet food manufacturers are already applying such a ban on a voluntary basis. 22



http://www.bseinquiry.gov.uk/report/volume11/chapter8.htm#808511



4.309 In a statement to the Inquiry, Dr Tyrrell said:

It was the rapid increase in the BSE epidemic, the occurrence of more cases of FSE and the results of the pig transmission experiment which led SEAC to give the advice we did on the extension of the SBO ban. Before then (September 1990), we were not asked to advise on the extension of the SBO ban. It was important to consider humans before other animals. It should be remembered that prior to the test results of the pig transmission experiment, pigs and poultry were not known to be susceptible to TSEs. Breeding pigs, in particular, were thought to have received a very high exposure to the same type of contaminated MBM as cattle but without any evidence of the occurrence of TSE. The issue of symptom-less hosts was considered very carefully because it could apply to all domestic and farmed animal species. 23



http://www.bseinquiry.gov.uk/report/volume11/chapter8.htm#808515




3.57 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.339 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.340 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.341 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. ***


3.58 There are several possible reasons why the experiment was not performed in the UK. It had been recommended by Sir Richard Southwood (Chairman of the Working Party on Bovine Spongiform Encephalopathy) in his letter to the Permanent Secretary of MAFF, Mr (now Sir) Derek Andrews, on 21 June 1988,342 though it was not specifically recommended in the Working Party Report or indeed in the Tyrrell Committee Report (details of the Southwood Working Party and the Tyrell Committee can be found in vol. 4: The Southwood Working Party, 1988–89 and vol. 11: Scientists after Southwood respectively). The direct inoculation of scrapie into calves was given low priority, because of its high cost and because it was known that it had already taken place in the USA.343 It was also felt that the results of such an experiment would be hard to interpret. While a negative result 337 Fraser, H., Bruce, M., Chree, A., McConnell, I. and Wells, G. (1992) Transmission of Bovine Spongiform Encephalopathy and Scrapie to Mice, Journal of General Virology, 73, 1891–7; Bruce, M., Chree, A., McConnell, I., Foster, J., Pearson, G. and Fraser, H. (1994) Transmission of Bovine Spongiform Encephalopathy and Scrapie to Mice: Strain Variation and the Species Barrier, Philosophical Transactions of the Royal Society of London, Series B, Biological Sciences, 343, 405–11 338 Bruce, M., Will, R., Ironside, J., McConell, I., Drummond, D., Suttie, A., McCordie, L., Chree, A., Hope, J., Birkett, C., Cousens, S., Fraser, H. and Bostock, C. (1997) Transmissions to Mice Indicate that ‘New Variant’ CJD is Caused by the BSE Agent, Nature, 389, 498–501 339 Clark, W., Hourrigan, J. and Hadlow, W. (1995) Encephalopathy in Cattle Experimentally Infected with the Scrapie Agent, American Journal of Veterinary Research, 56, 606–12 340 YB88/10.00/1.1 341 Cutlip, R., Miller, J., Race, R., Jenny, A., Katz, J., Lehmkuhl, H., Debey, B. and Robinson, M. (1994) Intracerebral Transmission of Scrapie to Cattle, Journal of Infectious Diseases, 169, 814–20 342 YB88/6.21/1.2 343 YB88/11.17/2.4 SCIENCE 84 would be informative, a positive result would need to demonstrate that when scrapie was transmitted to cattle, the disease which developed in cattle was the same as BSE.344 Given the large number of strains of scrapie and the possibility that BSE was one of them, it would be necessary to transmit every scrapie strain to cattle separately, to test the hypothesis properly. Such an experiment would be expensive. Secondly, as measures to control the epidemic took hold, the need for the experiment from the policy viewpoint was not considered so urgent. It was felt that the results would be mainly of academic interest.345 3.59 Nevertheless, from the first demonstration of transmissibility of BSE in 1988, the possibility of differences in the transmission properties of BSE and scrapie was clear. Scrapie was transmissible to hamsters, but by 1988 attempts to transmit BSE to hamsters had failed. Subsequent findings increased that possibility.



http://www.bseinquiry.gov.uk/pdf/volume2/chapter3.pdf





Monday, June 01, 2009

Biochemical typing of pathological prion protein in aging cattle with BSE



http://bse-atypical.blogspot.com/2009/06/biochemical-typing-of-pathological.html


Sunday, June 07, 2009

L-TYPE-BSE, H-TYPE-BSE, C-TYPE-BSE, IBNC-TYPE-BSE, TME, CWD, SCRAPIE, CJD, NORTH AMERICA



http://bse-atypical.blogspot.com/2009/06/l-type-bse-h-type-bse-c-type-bse-ibnc.html



Sunday, May 10, 2009

Identification and characterization of bovine spongiform encephalopathy cases diagnosed and NOT diagnosed in the United States



http://bse-atypical.blogspot.com/2009/05/identification-and-characterization-of.html



Sunday, December 28, 2008

MAD COW DISEASE USA DECEMBER 28, 2008 an 8 year review of a failed and flawed policy



http://bse-atypical.blogspot.com/2008/12/mad-cow-disease-usa-december-28-2008-8.html



Wednesday, August 20, 2008

Bovine Spongiform Encephalopathy Mad Cow Disease typical and atypical strains, was there a cover-up ?



http://bse-atypical.blogspot.com/2008/08/bovine-spongiform-encephalopathy-mad.html



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 SEAC 102/2



http://bse-atypical.blogspot.com/2009/02/new-results-on-idiopathic-brainstem.html



Saturday, June 13, 2009

BSE FEED VIOLATIONS USA UPDATE From 01/01/2009 To 06/10/2009



http://madcowfeed.blogspot.com/2009/06/bse-feed-violations-usa-update-from.html



Thursday, March 19, 2009

MILLIONS AND MILLIONS OF POUNDS OF MAD COW FEED IN COMMERCE USA



http://madcowfeed.blogspot.com/2009/03/millions-and-millions-of-pounds-of-mad.html



WHO WILL FOLLOW THE CHILDREN FOR CJD SYMPTOMS ???

Saturday, May 2, 2009

U.S. GOVERNMENT SUES WESTLAND/HALLMARK MEAT OVER USDA CERTIFIED DEADSTOCK DOWNER COW SCHOOL LUNCH PROGRAM



http://downercattle.blogspot.com/2009/05/us-government-sues-westlandhallmark.html



Sunday, April 12, 2009 BSE MAD COW TESTING USA 2009 FIGURES Month Number of Tests

Feb 2009 -- 1,891

Jan 2009 -- 4,620



http://www.aphis.usda.gov/newsroom/hot_issues/bse/surveillance/ongoing_surv_results.shtml



SEE FULL TEXT ;



http://madcowtesting.blogspot.com/2009/04/bse-mad-cow-testing-usa-2009-figures.html



Monday, May 4, 2009

Back to the Past With New TSE Testing Agricultural Research/May-June 2009



http://madcowtesting.blogspot.com/2009/05/back-to-past-with-new-tse-testing.html



Thursday, April 9, 2009

Docket No. FDA2002N0031 (formerly Docket No. 2002N0273) RIN 0910AF46 Substances Prohibited From Use in Animal Food or Feed; Final Rule: Proposed



http://madcowfeed.blogspot.com/2009/04/docket-no-fda2002n0031-formerly-docket.html



http://prionunitusaupdate2008.blogspot.com/2009/04/r-calf-and-usa-mad-cow-problem-dont.html#comments



Sunday, April 12, 2009 r-calf and the USA mad cow problem, don't look, don't find, and then blame Canada



http://prionunitusaupdate2008.blogspot.com/2009/04/r-calf-and-usa-mad-cow-problem-dont.html



http://prionunitusaupdate2008.blogspot.com/2009/04/cjd-foundation-sides-with-r-calfers-no.html#comments



Sunday, May 10, 2009

Meeting of the Transmissible Spongiform Encephalopathies Committee On June 12, 2009 (Singeltary submission)



http://tseac.blogspot.com/2009/05/meeting-of-transmissible-spongiform.html



Saturday, June 13, 2009

Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob disease in the United States 2003 revisited 2009

snip...



http://cjdusa.blogspot.com/2009/06/monitoring-occurrence-of-emerging-forms.html




Terry S. Singeltary Sr.

P.O. Box 42

Bacliff, Texas USA 77518