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