CHARACTERISATION OF SLOVENIAN OVINE ATYPICAL SCRAPIE CASES

CHARACTERISATION OF SLOVENIAN OVINE ATYPICAL SCRAPIE CASES


Juntes Polona1, Zabavnik Piano Jelka1, Cotman Marko1, Ambrožiè Ivan2 1University of Ljubljana, Veterinary Faculty, Slovenia 2MAFF, Veterinary Administration of Republic Slovenia, Slovenia

Introduction

Atypical scrapie is a form of scrapie described in sheep at first in 1998 in Norway (NOR 98), and later in a number of other countries, including very recently in New Zeeland and Australia. The first cases of atypical scrapie were found in Slovenia in 2010 and their characteristics are presented.

Materials and Methods

Brain samples were collected during routine monitoring for TSEs from sheep that died or were killed on farms. Atypical cases were found with rapid test, after that, several methods for characterisation were applied - three additional rapid tests, histopathology, immunohistochemistry, genotyping, and BSE/TSE discriminatory test.

Results

All tests which necessitate proteinase K digestion were negative, BSE and classical scrapie were excluded, but immunohistochemistry revealed pattern characteristic for NOR 98 atypical scrapie. Beside that, several ovine cases have been found which show somewhat different atypical immunostaining of cerebellum, and which were concluded as unconfirmed for TSE (not negative) after additional examination in the CRL for TSE.

Conclusions

Atypical scrapie can be expected in small ruminants in all countries but detection requires appropriate testing. Slovenian ovine atypical scrapie cases are similar to NOR 98 however we should be aware that other forms of atypical scrapie may appear.

http://www.esvp.eu/site/docs/pdf/ProceedingsBelgrade2010.pdf



usda scrapie report for April 2011 NEW ATYPICAL NOR-98 SCRAPIE CASE Pennsylvania AND California


POSITIVE SCRAPIE CASES

As of April 30, 2011, 14 cases of classical scrapie and 2 cases of Nor98-like scrapie were confirmed by the National Veterinary Services Laboratories (NVSL); 7 of the positive cases were Regulatory Scrapie Slaughter Surveillance (RSSS) cases (collected between October 1, 2010 and April 30, 2011 and confirmed by May 16, 2011) and 9 were field cases including 1 positive goat (Figure 6). With this positive, 22 cases of scrapie in goats have been confirmed by the NVSL since implementation of the regulatory changes in FY 2002 (Figure7).

http://www.aphis.usda.gov/animal_health/animal_diseases/scrapie/downloads/monthly_scrapie_rpt.ppsx



see map showing 2011 Nor-98 Scrapie cases shown by the asterisk, one blue and one green. why the different colors ??? again i would like to address to the USDA scrapie officials, just how terribly there maps are, in showing past scrapie cases. it's like if you don't catch them when they are first reported, you don't catch them at all. STILL, NO MAP SHOWS PAST SCRAPIE CASES ? it's like they are trying to hide the old cases as if they didn't happen $$$

also, please note, atypical Nor-98 scrapie cases are spreading in both Canada and the USA. Mexico, nobody knows anything about the TSE prion diseases down there ???

tss



Increased Atypical Scrapie Detections

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

http://gain.fas.usda.gov/Recent%20GAIN%20Publications/This%20Week%20in%20Canadian%20Agriculture%20%20%20%20%20Issue%2028_Ottawa_Canada_11-6-2009.pdf



The most recent assessments (and reassessments) were published in June 2005 (Table I; 18), and included the categorisation of Canada, the USA, and Mexico as GBR III. Although only Canada and the USA have reported cases, the historically open system of trade in North America suggests that it is likely that BSE is present also in Mexico.

http://www.oie.int/boutique/extrait/06heim937950.pdf



Sunday, March 27, 2011

SCRAPIE USA UPDATE FEBRUARY 2011

http://transmissiblespongiformencephalopathy.blogspot.com/2011/03/scrapie-usa-update-february-2011.html



Wednesday, February 16, 2011

IN CONFIDENCE

SCRAPIE TRANSMISSION TO CHIMPANZEES

IN CONFIDENCE

http://scrapie-usa.blogspot.com/2011/02/in-confidence-scrapie-transmission-to.html



Sunday, April 18, 2010

SCRAPIE AND ATYPICAL SCRAPIE TRANSMISSION STUDIES A REVIEW 2010

http://scrapie-usa.blogspot.com/2010/04/scrapie-and-atypical-scrapie.html



Monday, April 25, 2011

Experimental Oral Transmission of Atypical Scrapie to Sheep

Volume 17, Number 5-May 2011

http://nor-98.blogspot.com/2011/04/experimental-oral-transmission-of.html



Monday, November 30, 2009

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

http://nor-98.blogspot.com/2009/11/usda-and-oie-collaborate-to-exclude.html



I strenuously urge the USDA and the OIE et al to revoke the exemption of the legal global trading of atypical Nor-98 scrapie TSE. ...TSS




Friday, February 11, 2011

Atypical/Nor98 Scrapie Infectivity in Sheep Peripheral Tissues

http://nor-98.blogspot.com/2011/02/atypicalnor98-scrapie-infectivity-in.html



EVIDENCE OF SCRAPIE IN SHEEP AS A RESULT OF FOOD BORNE EXPOSURE

This is provided by the statistically significant increase in the incidence of sheep scrape from 1985, as determined from analyses of the submissions made to VI Centres, and from individual case and flock incident studies. ........

http://web.archive.org/web/20010305222246/www.bseinquiry.gov.uk/files/yb/1994/02/07002001.pdf



Thursday, December 23, 2010

Molecular Typing of Protease-Resistant Prion Protein in Transmissible Spongiform Encephalopathies of Small Ruminants, France, 2002-2009 Volume 17, Number 1 January 2011

http://transmissiblespongiformencephalopathy.blogspot.com/2010/12/molecular-typing-of-protease-resistant.html



Thursday, November 18, 2010

Increased susceptibility of human-PrP transgenic mice to bovine spongiform encephalopathy following passage in sheep

http://bse-atypical.blogspot.com/2010/11/increased-susceptibility-of-human-prp.html



Sunday, October 3, 2010

Scrapie, Nor-98 atypical Scrapie, and BSE in sheep and goats North America, who's looking ?

http://nor-98.blogspot.com/2010/10/scrapie-nor-98-atypical-scrapie-and-bse.html



*** In spite of the poorly defined effects of PRNP genetics, scrapie strain, dose, route and source of infection, the caprine placenta may represent a source of infection to progeny and herd mates as well as a source of persistent environmental contamination. ***




Could this route of infection be the cause of the many cases of Goat scrapie from the same herd in Michigan USA ?

Has this been investigated ?

(Figure 6) including five goat cases in FY 2008 that originated from the same herd in Michigan. This is highly unusual for goats, and I strenuously urge that there should be an independent investigation into finding the common denominator for these 5 goats in the same herd in Michigan with Scrapie. ...

Kind Regards, Terry



Thursday, January 07, 2010

Scrapie and Nor-98 Scrapie November 2009 Monthly Report Fiscal Year 2010 and FISCAL YEAR 2008

http://scrapie-usa.blogspot.com/2010/01/scrapie-and-nor-98-scrapie-november.html



In FY 2010, 72 cases of classical Scrapie and 5 cases of Nor-98 like Scrapie were confirmed...

http://www.aphis.usda.gov/animal_health/animal_diseases/scrapie/downloads/yearly_report.ppsx



Scrapie Nor-98 like case in California FY 2011 AS of December 31, 2010.

Scrapie cases in goats FY 2002 - 2011 AS of December 31, 2010 Total goat cases = 21 Scrapie cases, 0 Nor-98 like Scrapie cases (21 field cases, 0 RSSS cases)

Last herd with infected goats disignated in FY 2008 Michigan 8 cases

http://www.aphis.usda.gov/animal_health/animal_diseases/scrapie/downloads/monthly_scrapie_rpt.pps



SNIP...


SEE FULL TEXT ;



Tuesday, February 01, 2011

Sparse PrP-Sc accumulation in the placentas of goats with naturally acquired scrapie

Research article



http://scrapie-usa.blogspot.com/2011/02/sparse-prp-sc-accumulation-in-placentas.html



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




Monday, May 23, 2011

Atypical Prion Diseases in Humans and Animals 2011

Top Curr Chem (2011) DOI: 10.1007/128_2011_161 # Springer-Verlag Berlin Heidelberg 2011 Michael A. Tranulis, Sylvie L. Benestad, Thierry Baron, and Hans Kretzschmar

Abstract

Although prion diseases, such as Creutzfeldt–Jakob disease (CJD) in humans and scrapie in sheep, have long been recognized, our understanding of their epidemiology and pathogenesis is still in its early stages. Progress is hampered by the lengthy incubation periods and the lack of effective ways of monitoring and characterizing these agents. Protease-resistant conformers of the prion protein (PrP), known as the “scrapie form” (PrPSc), are used as disease markers, and for taxonomic purposes, in correlation with clinical, pathological, and genetic data. In humans, prion diseases can arise sporadically (sCJD) or genetically (gCJD and others), caused by mutations in the PrP-gene (PRNP), or as a foodborne infection, with the agent of bovine spongiform encephalopathy (BSE) causing variant CJD (vCJD). Person-to-person spread of human prion disease has only been known to occur following cannibalism (kuru disease in Papua New Guinea) or through medical or surgical treatment (iatrogenic CJD, iCJD). In contrast, scrapie in small ruminants and chronic wasting disease (CWD) in cervids behave as infectious diseases within these species. Recently, however, so-called atypical forms of prion diseases have been discovered in sheep (atypical/Nor98 scrapie) and in cattle, BSE-H and BSE-L. These maladies resemble sporadic or genetic human prion diseases and might be their animal equivalents. This hypothesis also raises the significant public health question of possible epidemiological links between these diseases and their counterparts in humans.

M.A. Tranulis (*)

Norwegian School of Veterinary Science, Oslo, Norway

e-mail: Michael.Tranulis@nvh.no

S.L. Benestad

Norwegian Veterinary Institute, Oslo, Norway

T. Baron

Agence Nationale de Se´curite´ Sanitaire, ANSES, Lyon, France

H. Kretzschmar

Ludwig–Maximilians University of Munich, Munich, Germany

Keywords Animal Atypical Atypical/Nor98 scrapie BSE-H BSE-L Human Prion disease Prion strain Prion type

http://resources.metapress.com/pdf-preview.axd?code=f433r34h34ugg617&size=largest




snip...SEE MORE HERE ;


http://bse-atypical.blogspot.com/2011/05/atypical-prion-diseases-in-humans-and.html




Sunday, May 01, 2011

STUDY OF ATYPICAL BSE 2010 Annual Report May 2011

http://bse-atypical.blogspot.com/2011/05/study-of-atypical-bse-2010-annual.html



Wednesday, June 01, 2011

Management of CWD in Canada: Past Practices, Current Conditions, Current Science, Future Risks and Options

http://chronic-wasting-disease.blogspot.com/2011/06/management-of-cwd-in-canada-past.html



Thursday, June 2, 2011

USDA scrapie report for April 2011 NEW ATYPICAL NOR-98 SCRAPIE CASES Pennsylvania AND California

http://nor-98.blogspot.com/2011/06/usda-scrapie-report-for-april-2011-new.html



TSS

NEW ATYPICAL NOR-98 SCRAPIE CASE DETECTED IDAHO NOW 5 CASES DOCUMENTED 2010

NEW ATYPICAL NOR-98 SCRAPIE CASE DETECTED IDAHO NOW 5 CASES DOCUMENTED 2010



Atypical Nor-98 states in this report AS OF AUGUST 2010 include ; Maine, Pennsylvania, Ohio, Oregon AND THE NEW STATE OF IDAHO NOW FALLING TO ATYPICAL NOR-98 SCRAPIE MAD SHEEP DISEASE. ...TSS


Infected and Source Flocks

As of July 31, 2010, there were 18 scrapie infected and source flocks with open statuses (Figure 3). One source flock was designated in July (Figure 4). In FY 2010, nine new infected flocks and eleven new source flocks were reported (Figure 5); 18 flocks completed a clean-up plan and were released (Figure 6). The ratio of infected and source flocks released to newly identified infected and source flocks for FY 2010 = .9 : 1.

New infected and source statuses from FY 1997 to FY 2010 are depicted in Chart 2.

Positive Scrapie Cases

As of July 31, 2010, 47 cases of classical scrapie and 5 cases of Nor98-like scrapie were confirmed by the National Veterinary Services Laboratories (NVSL); 30 were field cases and 22 were Regulatory Scrapie Slaughter Surveillance (RSSS) cases collected between October 1, 2009 and July 31, 2010 and confirmed by August 13,2010 (Figure 7). Of the five Nor98-like scrapie cases, four were RSSS cases and one was a field case. Field cases are positive animals tested as part of a disease investigation including potentially exposed, exposed, and suspect animals or tested as part of on farm surveillance. Three field cases were removed from the total count because the animals had been removed from an infected flock and been in quarantine at USDA's Agricultural Research Service (ARS) facility since 2008.

Twenty one cases of scrapie in goats have been confirmed by NVSL since implementation of the regulatory changes in FY 2002 (Figure 8). The most recent positive goat case was confirmed rectal biopsy positive in November 2009 and originated in the same herd in Michigan as the positive goat cases that were found in FY 2008. The positive goat had been held in quarantine for research by ARS since 2008 so is not shown on the FY 2010 map but is shown on the cumulative map of goat cases.

snip...


http://www.aphis.usda.gov/animal_health/animal_diseases/scrapie/downloads/monthly_scrapie_rpt.pps



Wednesday, March 3, 2010

NOR-98 ATYPICAL SCRAPIE USA 4 CASES DETECTED JANUARY 2010

http://nor-98.blogspot.com/2010/03/nor-98-atypical-scrapie-usa-4-cases.html



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



http://jvdi.org/cgi/content/full/21/4/454/VETD210405T01




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



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



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



all this i have documented here ;


see scrapie in CJD of humans (Davinpour et al, 1985) and more here ;


Sunday, April 18, 2010

SCRAPIE AND ATYPICAL SCRAPIE TRANSMISSION STUDIES A REVIEW 2010


http://scrapie-usa.blogspot.com/2010/04/scrapie-and-atypical-scrapie.html




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.long



[Although atypical scrapie is not yet ruled out, it is important to realize this is a type of scrapie that thus far has only tended to appear as a sporadic condition in older animals. Currently it has not been shown to follow the same genetic tendencies for propagation as the usual scrapie.

However, the atypical phenotypic appearance has been shown to be preserved on experimental passage.

Atypical scrapie was first identified in Norwegian sheep in 1998 and has subsequently been identified in many countries, as Australia may join that list. It is likely that this case will be sent to the UK for definitive conformation.

[Ref: M Simmons, T Konold, L Thurston, et al. BMC Veterinary Research 2010, 6:14 [provisional abstract available at ]

"Background ----------- "Retrospective studies have identified cases predating the initial identification of this form of scrapie, and epidemiological studies have indicated that it does not conform to the behaviour of an infectious disease, giving rise to the hypothesis that it represents spontaneous disease. However, atypical scrapie isolates have been shown to be infectious experimentally, through intracerebral inoculation in transgenic mice and sheep. [Many of the neurological diseases can be transmitted by intracerebral inoculation, which causes this moderator to approach intracerebral studies as a tool for study, but not necessarily as a direct indication of transmissibility of natural diseases. - Mod.TG]

"The 1st successful challenge of a sheep with 'field' atypical scrapie from an homologous donor sheep was reported in 2007.

"Results -------- "This study demonstrates that atypical scrapie has distinct clinical, pathological, and biochemical characteristics which are maintained on transmission and sub-passage, and which are distinct from other strains of transmissible spongiform encephalopathies in the same host genotype.

"Conclusions ------------ Atypical scrapie is consistently transmissible within AHQ homozygous sheep, and the disease phenotype is preserved on sub-passage."

Lastly, this moderator wishes to thank Terry Singletary for some of his behind the scenes work of providing citations and references for this posting. - Mod.TG]


http://www.promedmail.org/pls/otn/f?p=2400:1001:962575216785367::NO::F2400_P1001_BACK_PAGE,F2400_P1001_PUB_MAIL_ID:1000,81729




Peiffer, J. :

Gerstmann-Straussler's disease, atypical multiple sclerosis and carcinomas in a family of sheepbreeders.

Acta Neuropath. 56: 87-92, 1982. Peiffer (1982) described a family of sheepbreeders in which a father and 2 sons had GSS. All 3 also had congenital hip dysplasia, as did at least 3 other members of the kindred, all females. Atactic symptoms, dysarthria, and personality changes characterized the clinical course of this disorder, which might be labeled atypical multiple sclerosis. Like CJD , GSS is a form of subacute spongiform encephalopathy. Cases of GSS are clinically similar to the atactic type of CJD. Although there are many neuropathologic similarities, GSS differs from CJD by the presence of kuru-plaques and numerous multicentric, floccular plaques in the cerebral and cerebellar cortex, basal ganglia, and white matter. Whereas only 5 to 15% of CJD cases are familial, most cases of GSS are familial.


http://www.mad-cow.org/Alzheimer_cjd.html




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



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



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



Sunday, April 4, 2010

USDA AND OIE OUT OF TOUCH WITH RISK FACTOR ON ATYPICAL TSE


http://bseusa.blogspot.com/2010/04/usda-and-oie-out-of-touch-with-risk.html




URGENT DATA ON ATYPICAL BSE RISK FACTORS TO HUMANS AND ANIMALS OIE REFUSE TO ACKNOWLEDGE $

position: Post Doctoral Fellow Atypical BSE in Cattle

Closing date: December 24, 2009

Anticipated start date: January/February 2010

Employer: Canadian and OIE Reference Laboratories for BSE CFIA Lethbridge Laboratory, Lethbridge/Alberta

snip...

To date the OIE/WAHO assumes that the human and animal health standards set out in the BSE chapter for classical BSE (C-Type) applies to all forms of BSE which include the H-type and L-type atypical forms. This assumption is scientifically not completely justified and accumulating evidence suggests that this may in fact not be the case. Molecular characterization and the spatial distribution pattern of histopathologic lesions and immunohistochemistry (IHC) signals are used to identify and characterize atypical BSE. Both the L-type and H-type atypical cases display significant differences in the conformation and spatial accumulation of the disease associated prion protein (PrPSc) in brains of afflicted cattle. Transmission studies in bovine transgenic and wild type mouse models support that the atypical BSE types might be unique strains because they have different incubation times and lesion profiles when compared to C-type BSE. When L-type BSE was inoculated into ovine transgenic mice and Syrian hamster the resulting molecular fingerprint had changed, either in the first or a subsequent passage, from L-type into C-type BSE. In addition, non-human primates are specifically susceptible for atypical BSE as demonstrated by an approximately 50% shortened incubation time for L-type BSE as compared to C-type. Considering the current scientific information available, it cannot be assumed that these different BSE types pose the same human health risks as C-type BSE or that these risks are mitigated by the same protective measures.


http://www.prionetcanada.ca/detail.aspx?menu=5&dt=293380&app=93&cat1=387&tp=20&lk=no&cat2




Sunday, March 28, 2010

Nor-98 atypical Scrapie, atypical BSE, spontaneous TSE, trade policy, sound science ?


http://nor-98.blogspot.com/2010/03/nor-98-atypical-scrapie-atypical-bse.html



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




PUTTING THE NOR-98 ATYPICAL SCRAPIE CART BEFORE THE HORSE PUTS HUMAN AND ANIMAL LIVES AT RISK



SCRAPIE

The United States is unable to support the proposed new draft Code Chapter on Scrapie. The draft chapter, as written, departs significantly from the existing chapter, is confusing and is difficult to understand. This version of the scrapie chapter uses much of the same wording as the BSE chapter and is written as if the predominance of evidence revealed that scrapie was a food-borne disease similar to BSE in cattle which is inappropriate. Moreover, several of the new changes are not supported by current scientific evidence. As a result, detailed comments on individual articles would not meaningful at this time.

The United States is not supportive of the proposed draft chapter for the following reasons:

1. Inclusion of “atypical” scrapie: The scientific evidence indicates that “atypical” scrapie, also referred to as Nor-98, Nor-98-like, or non-classical scrapie, is not the same disease as classical scrapie. Further, “atypical” scrapie does not meet the criteria for listing diseases of trade concern by the OIE, as described in Chapter 2.1.1 of the Code. The United States recommends that the scope of this chapter be limited to classical scrapie in sheep and goats. Further, the United States recommends that OIE clearly adopt the position that “atypical” scrapie represents a distinct disease entity from classical scrapie and that it not be a listed disease.

• There is no evidence that “atypical” scrapie is a contagious disease. If it is contagious, available evidence suggests that it has a much lower transmission efficiency. (Hopp, et al, 2006; Green, et al, 2007; Benestad, et al 2008; McIntyre, et al, 2008)

• The disease appears to be ubiquitous in that it has been found wherever sufficient surveillance has been conducted. (Buschmann et al, 2004; De Bosschere et al, 2004; Orge, et al, 2004; Everest et al, 2006; Arsac, 2007; Benestad, et al 2008; Fediaevsky, et al, 2008)

• The disease does not appear to be economically significant in that the prevalence of clinical disease is low and it typically occurs in older animals. (Luhken, et al., 2007; Benestad, et al 2008).

• The disease is as likely as not to be the result of a spontaneous conversion of normal prion protein. (Benestad, et al 2008, De Bosschere et al 2007)

• Removal of exposed sheep is unlikely to reduce the prevalence of “atypical” scrapie infection and removing only those exposed sheep that are phenylalanine (F) at codon 141 is scientifically unsound since the disease is known to affect sheep of most other genotypes. Further, sheep with AHQ alleles have a similar risk of infection with “atypical” strains as sheep with F at codon 141. (Luhken, et al., 2007).

• If “atypical” scrapie is included as a listed disease, the surveillance and diagnostic requirements which are needed to identify these cases should be described in detail in both this Chapter and the Manual of Diagnostic Tests and Vaccines for Terrestrial

2

Animals. Data from Europe illustrates that using the proper test(s) is essential for the identification of atypical scrapie (Fediaevsky et al., 2008).

SNIP...

6. Overemphasis on importation and use of bovine meat and bone meal as a route of scrapie transmission: Given that the draft Chapter is not intended to address risk mitigation for BSE in small ruminants, we believe there is an over-emphasis on this potential route of transmission in the current draft.

The United States recommends that the requirements in this chapter be limited to the inclusion of products from sheep and goats (instead of from all ruminants) in feed or feed ingredients intended for consumption by animals

• The use of products from sheep and goats as feed or feed ingredients for ruminant or non-ruminant animals represent one possible route of transmission (Philippe, et al, 2005) and a source of environmental contamination with the classical scrapie agent. However, this is not the primary route of transmission for the scrapie agent.

• The need for the exclusion of cattle-derived protein or other animal protein to mitigate BSE risk should be based on a country’s BSE risk status and should be addressed in Chapter 2.3.13 of the Code.

SNIP...

14. Failure to provide scientific justification for the list of permitted commodities in Item 1 of Article 2.4.8.1. .

We recommend that the list be re-evaluated and those items that have not been substantiated as presenting no risk be excluded or those with some risk but where the intended use mitigates the risk the use be specified.

• There is no known human health risk associated with scrapie. As such, if meat and meat products for human consumption are included in this list, sheep and/or goat milk intended for human consumption should also be added to the list of permitted commodities in Item 1 of Article 2.4.8.1.

• In the vast majority of sheep infected with classical scrapie, actual infectivity or PrPres has been identified in most tissues including the lymphoreticular system (tonsils, spleen, lymph nodes), the gastrointestinal tract, brain, and spinal cord (Hadlow et. al. 1979; Hadlow et al., 1980; van Kuelen et al., 1996; van Kuelen et al., 1999, Andreoletti et al., 2000; Heggebø et al., 2002; Caplazi et al., 2004). Infectivity and/or PrPres has also been identified in the placenta (see Hourrigan et al., 1979; Onodera et al., 1993; Pattison et al., 1972; Pattison et al., 1974; Race et al., 1998), blood (Hunter et al., 2002; Houston et al. 2008); peripheral nerves (Groschup et al., 1996), muscle (Pattison and Millson, 1962; Andreoletti et al., 2004; Casalone et al., 2005), salivary gland (Hadlow et al., 1980; Vascellari et al., 2007), kidney (Siso et al., 2006), and skin ( Thomzig et al., 2007). In addition, recent work has shown milk and/or colostrum from scrapie infected ewes transmitted the disease to 17 of 18 lambs (Konold et al., 2008).

• The data on the risk of low protein tallow made from scrapie infected tissues particularly for use in milk replacer is limited and some epidemiologic studies suggest an association of milk replacer use with scrapie risk. Taylor et al., 1997 examined the inactivation capacity of different rendering system in regards to scrapie. The presence of infectivity was determined by bioassay into mice. From the onset of this study, it was assumed that tallow was not the vehicle for the transmission of TSE. Hence only 2 tallow samples were examined.


http://www.aphis.usda.gov/import_export/animals/oie/downloads/tahc_mar-sep08/tahc-scrapie-77-mar08_cmt.pdf



USDA's Deputy Secretary Talks with Sheep Producers

May 1, 2009 - "Life in rural America is intimately integrated with production agriculture," said Kathleen Merrigan, deputy secretary for the U.S. Department of Agriculture (USDA), when she addressed the more than 50 sheep producers from around the country who were in Washington, D.C., this week. "I am very interested in looking for new ways for farmers to market their products and for them to grab a little more of the food dollar. The connection between the food that consumers eat and the farms that the food is grown on must be closer, and I look forward to working with producers to affect that."

snip...

According to Jere Dick, DVM, associate deputy administrator and chief of field operations for the Animal and Plant Health Inspection Service (APHIS), "We anticipate discussions and hopefully revisions of the scrapie chapter at the World Organization for Animal Health meeting this month. The revisions will likely exclude Nor-98 like scrapie from classical scrapie regulations. If this is done, APHIS will be able to exempt flocks with Nor-98 like scrapie cases, should they occur, from extensive flock depopulation actions."

snip...end


http://sheepusa.org/?page=site/newsandevents&nav_id=c806da768c6fcc2652eee0967bc96b5a#772efce63bd783bb5da167cf744f349a




Monday, November 30, 2009


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


http://nor-98.blogspot.com/2009/11/usda-and-oie-collaborate-to-exclude.html




OIE Scrapie Chapter Revision • Current draft recognizes Nor98-like scrapie as a separate disease from classical scrapie • USDA provided comments on the draft to OIE


http://www.animalagriculture.org/Solutions/Proceedings/Annual%20Meeting/2009/Sheep%20&%20Goat/Myers,%20Thomas.pdf




Atypical scrapie/Nor 98 October 2009

Last year, after examining member country submissions and investigating rigorous scientific research, the World Organisation for Animal Health (OIE) decided that Nor 98 should not be listed in its Terrestrial Animal Health Code. The Code sets out trade recommendations or restrictions for listed diseases or conditions, and the OIE determined there was no need for such recommendations around Nor 98.


http://www.nzfsa.govt.nz/publications/ce-column/ce-web-nor98.htm



http://www.biosecurity.govt.nz/files/pests/atypical-scrapie/atypical-scrapie-faq-oct09.pdf



Sutton reported that USDA has urged the World Organization for Animal Health (OIE) to categorize Nor98-like scrapie as a separate disease from classical scrapie. Currently, the OIE has proposed a draft revision of their scrapie chapter that would exclude Nor98-like scrapie from the chapter. USDA will be submitting it's comments on this proposal soon.


http://www.ohiosheep.org/Events/ScrapieNewsletterMarch09.pdf




FULL TEXT ;


http://nor-98.blogspot.com/2009/11/usda-and-oie-collaborate-to-exclude.html





Saturday, June 5, 2010

Research Project: Transmissible Spongiform Encephalopathies: Identification of atypical scrapie in Canadian sheep


http://nor-98.blogspot.com/2010/06/research-project-transmissible.html




hmmm, this is getting interesting now...



Sporadic CJD type 1 and atypical/ Nor98 scrapie are characterized by fine (reticular) deposits,

see also ;

All of the Heidenhain variants were of the methionine/ methionine type 1 molecular subtype.


http://cjdusa.blogspot.com/2009/09/co-existence-of-scrapie-prion-protein.html




Tuesday, July 29, 2008

Heidenhain Variant Creutzfeldt Jakob Disease Case Report

snip...

Heidenhain Variant Creutzfeldt Jakob Disease autopsy case report 'MOM'

DIVISION OF NEUROPATHOLOGY University of Texas Medical Branch 114 McCullough Bldg. Galveston, Texas 77555-0785

FAX COVER SHEET

DATE: 4-23-98

TO: Mr. Terry Singeltary @ -------

FROM: Gerald Campbell

FAX: (409) 772-5315 PHONE: (409) 772-2881

Number of Pages (including cover sheet):

Message:

*CONFIDENTIALITY NOTICE*

This document accompanying this transmission contains confidential information belonging to the sender that is legally privileged. This information is intended only for the use of the individual or entry names above. If you are not the intended recipient, you are hereby notified that any disclosure, copying distribution, or the taking of any action in reliances on the contents of this telefaxed information is strictly prohibited. If you received this telefax in error, please notify us by telephone immediately to arrange for return of the original documents. -------------------------- Patient Account: 90000014-518 Med. Rec. No.: (0160)118511Q Patient Name: POULTER, BARBARA Age: 63 YRS DOB: 10/17/34 Sex: F Admitting Race: C

Attending Dr.: Date / Time Admitted : 12/14/97 1228 Copies to:

UTMB University of Texas Medical Branch Galveston, Texas 77555-0543 (409) 772-1238 Fax (409) 772-5683 Pathology Report

FINAL AUTOPSY DIAGNOSIS Autopsy' Office (409)772-2858

Autopsy NO.: AU-97-00435

AUTOPSY INFORMATION: Occupation: Unknown Birthplace: Unknown Residence: Crystal Beach Date/Time of Death: 12/14/97 13:30 Date/Time of Autopsy: 12/15/97 15:00 Pathologist/Resident: Pencil/Fernandez Service: Private Restriction: Brain only

FINAL AUTOPSY DIAGNOSIS

I. Brain: Creutzfeldt-Jakob disease, Heidenhain variant.



snip...see full text ;


http://creutzfeldt-jakob-disease.blogspot.com/2008/07/heidenhain-variant-creutzfeldt-jakob.html




Monday, December 14, 2009

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


http://nor-98.blogspot.com/2009/12/similarities-between-forms-of-sheep.html




EVIDENCE OF SCRAPIE IN SHEEP AS A RESULT OF FOOD BORNE EXPOSURE

This is provided by the statistically significant increase in the incidence of sheep scrape from 1985, as determined from analyses of the submissions made to VI Centres, and from individual case and flock incident studies. ........

http://web.archive.org/web/20010305222246/www.bseinquiry.gov.uk/files/yb/1994/02/07002001.pdf



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

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

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

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

snip...

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

PMID: 6997404

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



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

Transmission of scrapie to the cynomolgus monkey (Macaca fascicularis). Gibbs CJ Jr, Gajdusek DC.

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

Transmission of Scrapie to the Cynomolgus Monkey (Macaca fascicularis)

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

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

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

http://www.nature.com/nature/journal/v236/n5341/abs/236073a0.html



Epidemiology of Scrapie in the United States 1977

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

http://web.archive.org/web/20030513212324/http://www.bseinquiry.gov.uk/files/mb/m08b/tab64.pdf



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




Then follow up with PNAS studies from which new scientist article written from;

Published online before print March 20, 2001 Proc. Natl. Acad. Sci. USA, 10.1073/pnas.041490898 Abstract of this Article Reprint (PDF) Version of this Article Similar articles found in: PNAS Online PubMed PubMed Citation Search Medline for articles by: Lasmézas, C. I. Deslys, J.-P. Alert me when: new articles cite this article Download to Citation Manager Neurobiology

Adaptation of the bovine spongiform encephalopathy agent to primates and comparison with Creutzfeldt- Jakob disease: Implications for human health

Corinne Ida Lasmézas*, [dagger] , Jean-Guy Fournier*, Virginie Nouvel*, Hermann Boe*, Domíníque Marcé*, François Lamoury*, Nicolas Kopp [Dagger ] , Jean-Jacques Hauw§, James Ironside¶, Moira Bruce [] , Dominique Dormont*, and Jean-Philippe Deslys*

* Commissariat à l'Energie Atomique, Service de Neurovirologie, Direction des Sciences du Vivant/Département de Recherche Medicale, Centre de Recherches du Service de Santé des Armées 60-68, Avenue du Général Leclerc, BP 6, 92 265 Fontenay-aux-Roses Cedex, France; [Dagger ] Hôpital Neurologique Pierre Wertheimer, 59, Boulevard Pinel, 69003 Lyon, France; § Laboratoire de Neuropathologie, Hôpital de la Salpêtrière, 83, Boulevard de l'Hôpital, 75013 Paris, France; ¶ Creutzfeldt-Jakob Disease Surveillance Unit, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, United Kingdom; and [] Institute for Animal Health, Neuropathogenesis Unit, West Mains Road, Edinburgh EH9 3JF, United Kingdom

Edited by D. Carleton Gajdusek, Centre National de la Recherche Scientifique, Gif-sur-Yvette, France, and approved December 7, 2000 (received for review October 16, 2000)

Abstract Top Abstract Introduction Materials and Methods Results Discussion Conclusions References

There is substantial scientific evidence to support the notion that bovine spongiform encephalopathy (BSE) has contaminated human beings, causing variant Creutzfeldt-Jakob disease (vCJD). This disease has raised concerns about the possibility of an iatrogenic secondary transmission to humans, because the biological properties of the primate-adapted BSE agent are unknown. We show that (i) BSE can be transmitted from primate to primate by intravenous route in 25 months, and (ii) an iatrogenic transmission of vCJD to humans could be readily recognized pathologically, whether it occurs by the central or peripheral route. Strain typing in mice demonstrates that the BSE agent adapts to macaques in the same way as it does to humans and confirms that the BSE agent is responsible for vCJD not only in the United Kingdom but also in France. The agent responsible for French iatrogenic growth hormone-linked CJD taken as a control is very different from vCJD but is similar to that found in one case of sporadic CJD and one sheep scrapie isolate. These data will be key in identifying the origin of human cases of prion disease, including accidental vCJD transmission, and could provide bases for vCJD risk assessment.

Introduction Top Abstract Introduction Materials and Methods Results Discussion Conclusions References

The recognition of a variant of the human transmissible spongiform encephalopathy (TSE) Creutzfeldt-Jakob Disease (vCJD) in the U.K. in 1996 raised the major concern that it would correspond to human infection with the agent responsible for bovine spongiform encephalopathy (BSE; ref. 1). Transmission of BSE to macaques provided the first experimental evidence as it produced a disease close to vCJD in humans (2). Strain typing in inbred mice (consisting of measuring the incubation period and establishing lesion profiles corresponding to the strain-specific distribution of brain vacuolation) allows reliable identification of TSE strains (3). This method, together with biochemical methods, has revealed a single phenotype for the agents of BSE and the British cases of vCJD (4-6). Mice expressing only the bovine prion protein (PrP) were highly susceptible to vCJD and BSE, which induced the same disease (7). Thus, it is now well established that BSE has caused vCJD, probably by alimentary contamination. In this respect, the finding of abnormal PrP labeling in the gastrointestinal tract and lymphatic tissues of orally BSE-contaminated lemurs shows that the BSE agent can infect primates by the oral route (8). About 1 million contaminated cattle may have entered the human food chain, and the future number of vCJD cases could range from 63 to 136,000 depending on the incubation period of BSE in humans (9). Unlike sporadic CJD (sCJD) and iatrogenic CJD (iCJD) linked to the administration of contaminated growth hormone extracted from human hypophyses, in vCJD, the infectious agent seems to be widely distributed in lymphoid organs, as pathological PrP (PrPres) can be detected in tonsils, lymph nodes, spleen, and appendix even in the preclinical phase of the disease (10, 11). This raises a public health issue with regard to the risk of iatrogenic transmission of vCJD through surgical instruments, grafts, blood transfusion, or parenteral administration of biological products of human origin. However, this risk is difficult to assess, because it largely depends on factors such as the virulence of the BSE agent adapted to primates and the efficiency of secondary transmission to humans by a peripheral route such as the i.v. one. A further issue is whether vCJD accidentally acquired from humans would be recognized. The latter poses the question of a phenotypic variation of the BSE agent after successive transmissions in humans: does it retain its strain characteristics, and does it induce a pathology similar to that observed in the previous host? A 9-year history of transmission of BSE to primates and mice enables us today to clarify a number of these important points.

Although BSE has mainly affected the U.K., two definite cases and one probable case of vCJD have now been reported in France in people who have never resided in the U.K. (12, 13). We strain-typed the first of these cases to establish its origin. Strain typing in C57BL/6 mice of BSE, French, and British vCJD was compared with that of BSE passaged in nonhuman primates, thus allowing us to study the effect of serial passages in primates. Comparisons were also made with French cases of sCJD and iCJD and two strains of scrapie (one of French and one of U.S. origin). Our findings provide experimental demonstration that the same agent, namely that responsible for the cattle disease BSE, has caused vCJD both in France and in the U.K., in line with biochemical data and with the fact that, until 1996, about 10% of the beef consumed in France was imported from the U.K. We found that the BSE agent in nonhuman primates is similar to that causing vCJD in humans and tends to evolve rapidly toward a primate-adapted variant. Furthermore, we showed that the strain responsible for iCJD is closely related to that of one patient with sCJD, and, more unexpectedly, that these agents were similar to the French scrapie strain studied (but different from the U.S. scrapie strain). This finding requires a cautious interpretation for several reasons, not least because of the inevitably limited number of TSE strains that can be studied by such a cumbersome method as strain typing. Nonetheless, it also prompts reconsideration of the possibility that, in some instances, sheep and human TSEs can share a common origin.

snip...

http://www.pnas.org/cgi/content/full/041490898v1




The BSE Inquiry / Statement No 410 Dr Helen Grant Issued 13/05/1999 (not scheduled to give oral evidence) BSE INQUIRY STATEMENT OF DR HELEN GRANT MD FRCP

1. My credentials in the matters of BSE and CJD are: a. 1970-1982 Consultant Neuropathologist at the Middlesex Hospital. b. 1985-1989 Consultant Neuropathologist at the Charing Cross Hospital. c. I have carried out six autopsies on CJD victims and reported on a similar number of cerebral biopsies from CJD patients. 1. Through my interest in slow viruses (particularly with reference to multiple sclerosis) I was one of only a few people to be aware of both Scrapie and CJD in 1988. 2

. I have never had any formal links with the farming community, renderers, pet food manufacturers, etc. However, slaughterhouse workers began telephoning me as early as February 1989 after they learned through the media of my concern and knowledge about TSEs. Several of them rang me because they had had no instructions from the Health and Safety Executive about precautions to be taken to avoid infection from BSE carcases. (I have kept some of the correspondence with these workers together with my list of precautions to be taken in abattoirs).

3. I asked the slaughterhouses workers in detail to explain the routine slaughtering practices and was astonished to learn that sheep’s brains were generally left inside the skull whereas cattle brains were routinely removed to be added to our "meat products" – meat pies, pates, tinned items and stock cubes. I therefore feared that this almost indestructible infective agent was being swallowed by all beef eaters in the UK in large doses which would inevitably infect genetically susceptible people.

4. I was horrified because I suddenly realised why Government assurances about BSE – namely "we have lived with scrapie for two-and-a-half centuries and it has not done us any harm so we won’t have any trouble with BSE" – were based on a false premise which was that cattle brains and sheep’s brains were dealt with in the same way in the abattoirs which they obviously were not. Since sheep’s brains were seldom removed from the skulls (which is why cattle caught scrapie in the first place) we humans have never been seriously exposed over the centuries to the scrapie agent. Simple economics is the reason: sheep’s brains are too small to make the intricate process of their removal worthwhile.

5. I appeared on the BBC nine o’clock television news on February 27, 1989 (the day the Southwood Report was published) in my capacity as consultant neuropathologist at Charing Cross hospital. I was asked among other things to comment on the possible human hazard of BSE and I warned that I thought there was a risk because cattle brains were going into our food chain. I added: "Who knows? Some of us may be incubating it already." Some of us were.

6. I was called to give evidence to the House of Commons Agriculture Select Committee on 13 June 1990 (IBD 1 Tab 7 p 42). On re-reading it, I see no reason to change anything in my evidence except the numbers of animals mentioned. The Government of the day was hardly disposed to ask my advice about BSE on a regular basis given my critical attitude since early 1989. But the then Labour Opposition, understandably anxious for information, turned to me frequently. Opposition Members included David Clark MP, Ron Davies MP and Ian McCartney MP. It was my technical information which helped Ron Davies MP to make his effective speech about BSE in the House of Commons on 17 May 1989 (M 7 Tab 7). Shortly afterwards, the Minister for Agriculture, John MacGregor, announced that legislation would be brought in to ban all cattle brains from human food (YB 89/6.13/5.1-5.2). The long summer recess delayed this legislation and the "specified offals" ban was finally enacted on 9 November 1989 (L2 Tab 4) (9 February 1990 in Scotland) (L10 Tab 9). Of course this was more than a year (15 months) after cattle had been protected in the same way.

7. Apart from my involvement with CJD I have of course been interested in that worldwide scourge, multiple sclerosis (MS). This led me to ponder the question of "slow virus infection – now labelled "prion infection" (an inaccurate title. In my opinion prion is a short title for an organism which causes Transmissible Spongiform Encephalopathy (TSE) such as scrapie, CJD, BSE, Kuru and others. Prion diseases has therefore become widely used instead of the cumbersome alternative (YB 94/4.25/10.1)) – which is one of the aetiological factors involved in MS. Scrapie, the ovine TSE, was then and still is by far the most extensively researched slow virus infection. I therefore read up all the papers on the subject as they appeared during the 1950s, ‘60s and ‘70s and was therefore immediately aware of the human hazard posed by the BSE catastrophe. Vets generally did not know about CJD (why should they?) and neuropathologists were mostly ignorant of scrapie. I happened to know about both in those early days due to my interest in "slow viruses".

8. I was in receipt of no extra funds beyond those provided by the NHS and the University of London to run my laboratories and pay my salary as a senior lecturer/honorary Consultant and I suffered no constraints over my publications, lectures to my students, or statements to the media. However, I became increasingly aware after 1988 that questioning official dogma about BSE brought difficulties to one’s career. I was myself about to retire from the Charing Cross Hospital, where I worked as a Consultant Neuropathologist, but I observed with horror that the good reputations of dissenting scientists in the field, not least Dr Stephen Dealler and especially Dr Harash Narang were systematically undermined.

9. My primary function has been to teach medical under-graduates and post-graduates about diseases of the brain and nervous system and, of course, to fulfil my clinical functions as a consultant neuropathologist at two London teaching hospitals. This, of course, meant that I conducted both biopsies and autopsies including those on patients with CJD: it was not primarily to publish scientific articles. My scientific publications include only one case which I think in retrospect may be CJD before that was known to be an infection with this agent. ("Post Traumatic Dementia": Helen C Grant, Behrman et al. Archiv für Psyciatre und Zeitschrift für die ges. Neurologie. 1965; 207: 128) More importantly I have carried out several biopsies and autopsies on CJD patients. My duties also included the initiation and supervision of research projects. When my trainees and PhD students published their resulting scientific papers I took the view that the work was theirs, they should get the credit (not I) and therefore I made it a matter of principle not to add my name as co-author.

10. I corresponded frequently from February 1989 onwards with Government ministers including John MacGregor, Donald Thomson, Gillian Shepherd and Angela Browning. But I received only short and reassuring replies containing what I believed to be inaccurate information. Because official bodies treated my early warnings with hostility, I soon learned that the only way to convey my concerns was to contribute relevant letters to the broadsheet newspapers and to speak to responsible members of the press, the broadcasting services and informed members of Opposition parties.

11. Since February 1989 I have answered innumerable letters from members of the public understandably anxious – if not panicky – about the effect on their diets of the outbreak. They came/come from a cross-section of the community: parents ("is the milk safe?"), restaurateurs, doctors, butchers, journalists, Education Committees. Since I retired finally in March 1989 I have had the time to answer them all eventually.

12. The BSE/CJD problem is quite incomprehensible without knowledge of the facts set out in Annex 1. The infective agent has unique and sinister properties.

Issued on behalf of the witness by: The BSE Inquiry Press Office 6th Floor Hercules House Hercules Road London SE1 7DU Fax: 0171 803 0893 Website: http://www.bse.org.uk Email: inquiry@bse.org.uk



http://collections.europarchive.org/tna/20080102135133/http://www.bseinquiry.gov.uk/files/ws/s410.pdf



http://web.archive.org/web/20040314215449/www.bseinquiry.gov.uk/files/ws/s410x.pdf




Wednesday, August 18, 2010

Incidence of CJD Deaths Reported by CJD-SS in Canada as of July 31, 2010


http://creutzfeldt-jakob-disease.blogspot.com/2010/08/incidence-of-cjd-deaths-reported-by-cjd.html




Monday, August 9, 2010

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

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


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




Thursday, August 19, 2010

SCRAPIE CANADA UPDATE Current as of 2010-07-31 The following table lists sheep flocks and/or goat herds confirmed to be infected with scrapie in Canada in 2010.

Current as of: 2010-07-31


http://nor-98.blogspot.com/2010/08/scrapie-canada-update-current-as-of.html



Wednesday, August 11, 2010

REPORT ON THE INVESTIGATION OF THE SIXTEENTH CASE OF BOVINE SPONGIFORM ENCEPHALOPATHY (BSE) IN CANADA


http://bse-atypical.blogspot.com/2010/08/report-on-investigation-of-sixteenth.html



Thursday, August 19, 2010

REPORT ON THE INVESTIGATION OF THE SEVENTEENTH CASE OF BOVINE SPONGIFORM ENCEPHALOPATHY (BSE) IN CANADA


http://bseusa.blogspot.com/2010/08/report-on-investigation-of-seventeenth.html





This new prionopathy in humans? the genetic makeup is IDENTICAL to the g-h-BSEalabama mad cow, the only _documented_ mad cow in the world to date like this, ......wait, it get's better. this new prionpathy is killing young and old humans, with LONG DURATION from onset of symptoms to death, and the symptoms are very similar to nvCJD victims, OH, and the plaques are very similar in some cases too, bbbut, it's not related to the g-h-BSEalabama cow, WAIT NOW, it gets even better, the new human prionpathy that they claim is a genetic TSE, has no relation to any gene mutation in that family. daaa, ya think it could be related to that mad cow with the same genetic make-up ??? there were literally tons and tons of banned mad cow protein in Alabama in commerce, and none of it transmitted to cows, and the cows to humans there from ??? r i g h t $$$



Rural and Regional Affairs and Transport References Committee The possible impacts and consequences for public health, trade and agriculture of the Government’s decision to relax import restrictions on beef Final report June 2010



2.65 At its hearing on 14 May 2010, the committee heard evidence from Dr Alan Fahey who has recently submitted a thesis on the clinical neuropsychiatric, epidemiological and diagnostic features of Creutzfeldt-Jakob disease.48 Dr Fahey told the committee of his concerns regarding the lengthy incubation period for transmissible spongiform encephalopathies, the inadequacy of current tests and the limited nature of our current understanding of this group of diseases.49



2.66 Dr Fahey also told the committee that in the last two years a link has been established between forms of atypical CJD and atypical BSE. Dr Fahey said that: They now believe that those atypical BSEs overseas are in fact causing sporadic Creutzfeldt-Jakob disease. They were not sure if it was due to mad sheep disease or a different form. If you look in the textbooks it looks like this is just arising by itself. But in my research I have a summary of a document which states that there has never been any proof that sporadic Creutzfeldt-Jakob disease has arisen de novo—has arisen of itself. There is no proof of that. The recent research is that in fact it is due to atypical forms of mad cow disease which have been found across Europe, have been found in America and have been found in Asia. These atypical forms of mad cow disease typically have even longer incubation periods than the classical mad cow disease.50



http://www.aph.gov.au/senate/committee/rrat_ctte/mad_cows/report/report.pdf




ALABAMA MAD COW g-h-BSEalabama



In this study, we identified a novel mutation in the bovine prion protein gene (Prnp), called E211K, of a confirmed BSE positive cow from Alabama, United States of America. This mutation is identical to the E200K pathogenic mutation found in humans with a genetic form of CJD. This finding represents the first report of a confirmed case of BSE with a potential pathogenic mutation within the bovine Prnp gene. We hypothesize that the bovine Prnp E211K mutation most likely has caused BSE in "the approximately 10-year-old cow" carrying the E221K mutation.



http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1000156




http://www.plospathogens.org/article/fetchObjectAttachment.action?uri=info%3Adoi%2F10.1371%2Fjournal.ppat.1000156&representation=PDF




Saturday, August 14, 2010

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

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



http://prionpathy.blogspot.com/2010/08/bse-case-associated-with-prion-protein.html





g-h-BSE-alabama E211K mad cows USA how many would that be annually ???


if our ciphering is correct (?), that would be about 35 g-h-BSE-alabama E211K mad cows going into the food chain a year.

an incidence of less than 1 in 2000.

let's see, that's 500 such per million.

or 50,000 cows per 100 million (US herd size).

even at less than 1 in a million, with 35 million slaughtered, that's 35 infected cows going into the food chain each year.

hmmm, friendly fire there from ???




Wednesday, July 28, 2010

re-Freedom of Information Act Project Number 3625-32000-086-05, Study of Atypical BSE UPDATE July 28, 2010



http://bse-atypical.blogspot.com/2010/07/re-freedom-of-information-act-project.html




Tuesday, August 03, 2010

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



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




Monday, August 9, 2010

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



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




Thursday, August 12, 2010

Seven main threats for the future linked to prions



http://prionpathy.blogspot.com/2010/08/seven-main-threats-for-future-linked-to.html



http://prionpathy.blogspot.com/






TSS

Atypical/Nor98 scrapie in the Basque Country: a case report of eight outbreaks

Subject: Atypical/Nor98 scrapie in the Basque Country: a case report of eight outbreaks

Atypical/Nor98 scrapie in the Basque Country: a case report of eight outbreaks

Since 2002, an active surveillance program for transmissible spongiform encephalopathy in small ruminants in European Union countries allowed identification of a considerable number of atypical cases in small ruminant with similarities to the previously identified atypical scrapie cases termed Nor98.

Results: Here we report molecular and neuropathological features of eight atypical/Nor98 scrapie cases detected between 2002 and 2009. Significant features of the affected sheep included: their relatively high ages (mean age 7.9 years, range between 4.3 and 12.8), their breed (all Latxa) and their PRNP genotypes (AFRQ/ALRQ, ALRR/ALRQ, AFRQ/AFRQ, AFRQ/AHQ, ALRQ/ALRH, ALRQ/ALRQ).

All the sheep were confirmed as atypical scrapie by immunohistochemistry and immunoblotting. Two cases presented more PrP immunolabelling in cerebral cortex than in cerebellum.

Conclusions: This work indicates that atypical scrapie constitutes the most common small ruminant transmissible spongiform encephalopathy form in Latxa sheep in the Spanish Basque Country.

Moreover, a new genotype (ALRQ/ALRH) was found associated to atypical scrapie.

Author: Ana Rodriguez-MartinezJoseba GarridoSonia MazaLeyre BenedictoMarivi GeijoNieves GomezEsmeralda MinguijonSylvie BenestadRamon Juste Credits/Source: BMC Veterinary Research 2010, 6:17


http://7thspace.com/headlines/339700/atypicalnor98_scrapie_in_the_basque_country_a_case_report_of_eight_outbreaks.html




another outbreak of spontaneous atypical scrapie ???



FURTHER INTO THIS STUDY ;



Case presentation

Between 2002 and 2008 the mean number of sheep analysed per year in the Basque Country was 764 and until September 2009, the total number of animals screened added up to 5620. Of these, eight Latxa ewes with molecular and pathological features of AS/Nor98 were found. The cases were detected widely distributed within this region and amounted to a significantly (p=0.0196) higher prevalence (0.15 %) than

6

that of classical scrapie (0.02 %) (Table 1). The first two cases were fallen stock and appeared in 2004, the third one was a slaughtered ewe tested in 2005 that was confirmed by Western blotting as Nor98 at the Norwegian National Veterinary Institute. The three following cases were detected in 2008, the first two cases at the beginning of the year and the third at the end of the year. The two last cases were detected at the beginning of 2009 and had been slaughtered for human consumption. Clinical symptoms were reported in only one of the cases (M31 (2008)). It drew the attention of the veterinary inspector at the slaughterhouse because it showed slight neurological signs such as ataxia, and poor condition. There were no further veterinary inspection reports of clinical signs for the remaining slaughtered animals or any of the fallen stock. In this context, it needs to be emphasized that due to frequent lack of clinical records as a consequence of the inefficiency of passive surveillance, there is no adequate clinical information on these scrapie cases in general. The mean age of all the eight cases was 7.9 years (range between 4.3 and 12.8).

SNIP...

We described eight atypical scrapie cases detected between 2002 and 2009 from the Basque Country. All AS/Nor98 cases were found in Latxa sheep which breed represents 85% of the Basque Country sheep population [54,55,57]. The occurrence of these cases seemed to be random and, in agreement with other AS surveillance studies [22], there was no apparent temporal trend,. Geographically, the distribution of atypical scrapie cases was in accordance with that described in other regions of the world. First, a single positive sheep per affected flock was detected, as observed in the majority of other AS cases [1,19,20]. Second, they presented a wide distribution in the Basque Country, with reports of cases in all three provinces. At this point it should be mentioned that the highest proportion was observed in Guipuzcoa (62.5%) but it may be due to the fact that it constituted the province with the highest rate of sheep slaughter

9

(over 90%) analysed in the Basque Country. Nevertheless, the sample size was still too small to draw any definite conclusion. Moreover, the occurrence of atypical scrapie cases pointed to an absence of time clustering, since there were long periods with no detection of cases and then, within a few months 2 or 3 affected animals were detected. However, it must be taken into consideration that, (i) not all sheep older than 18 months of age were analysed as a consequence of the random sampling procedure contrary to the exhaustive one legislated for cattle, (ii) the brain sampling may not have been optimal, e.g. only the medulla oblongata was collected or, particularly in the case of fallen stock, the brain samples were sometimes severely autolytic and liquefied, thus increasing the chances of sampling an area where PrPSc was absent, (iii) due to the young age of some animals, the stage of the disease, the small sampling site and the relatively low number of animals and short period of time involved, the possibility of longer and more tenuous temporal and spatial trends in PrPSc distribution could not be excluded. For these reasons, the number of AS and CS cases may be underrepresented and could suffer from a certain bias. One of the cases (M45) described here was confirmed to be Nor98. PrPSc deposition, distribution and molecular profile of the cases M72, M31, M15, M9-1 and M9-2 were identical to the features of this Nor98-confirmed case and to previous descriptions [1,38]. Moreover, the mean age observed was in accordance to other observations for atypical scrapie [36]. Among some of the features our cases had in common with M45, the following should be emphasised: i) the molecular protein profile showed a characteristic low molecular weight band under 14 kDa, ii) the cerebellum was the most affected region, iii) PrPSc was mainly detected in the neuropil predominantly as fine granular deposits, and iv) a faint to moderate PrPSc signal intensity was seen. The detection of more intense PrPSc deposits in cerebellum or

10

cerebral cortex rather than in the medulla oblongata may indicate that the prion is likely not to enter the brain through the medulla (DMNV) as described for classical scrapie [58], thus suggesting a rather sporadic aetiology, as observed in human sporadic TSE cases. Cases M15 and M27 however, presented some differences. Albeit PrPSc molecular pattern was similar to the Nor98 confirmed case, both animals showed more PrPSc deposits in the frontal lobe of cerebral cortex than in the cerebellum by immunohistochemistry (IHC) and also by immunoblot (WB) for case M27. By contrast, case M15 showed small differences between IHC and WB results since the signal in the pooled obex and cerebellum in WB was more intense than in the cerebellum and medulla oblongata in IHC. This could have been biased by the sampling for frozen tissues and by severe tissue autolysis and could be the explanation for a negative and extremely faint PrPSc signal in WB of case M7 in the cerebellum and obex, respectively. The fact that these cases showed more PrPSc accumulation in cerebral cortex than in cerebellum might be influenced by other still unknown environmental or genetics factors. Alternatively, this might happen more commonly than observed because of the limited number of AS/Nor98 cases where both the cerebellar and the cerebral cortices are available for analysis. When the sampling of brain is carried out with a spoon through the foramen magnum some cerebellum can also be collected along with the medulla oblongata and this can be targeted as the optimum sample for WB testing, particularly if the IHC results indicate a possible atypical scrapie case. Unfortunately, cerebrum is not routinely collected by this method so little is known about its PrPSc status. The availability of this brain region for M7 would have been useful to clear up any doubt on its diagnosis and classification. This case was questionable because we did not obtain a clear pattern in the WB with the band lower than 14kDa size and because the detected signal in the cerebellum by means of IHC was extremely faint. The poor

11

condition of the sample and the scant material available did not allow us to obtain, after repetitions of the analyses, a clear evidence of being an AS/Nor98 case. The fact that it was confirmed for the National Reference Laboratory allowed arguing that it was a scrapie case. Besides, there were several features supporting it as an atypical scrapie case. First, for CS, we would have expected to obtain a more intense signal in the WB and a clear three bands pattern of PrPSc in the region of the obex [17]. Second, even not having an optimal signal in the WB that showed the lower band characteristic of atypical cases and having evidences according to which the case was positive by means of IHC and rapid test, the possibility of an atypical scrapie case should not be excluded. In this case, it could have happened that there was little amount of abnormal PrPSc so that after PK digestion the amount of resistant PrPSc was reduced considerably below the detection threshold of WB, as observed in the cerebellum of case M15. Third, the age of this sheep was higher than the mean age of CS cases described in Latxa breed [59] and in other breeds [60,61]. Finally, this was the only detected case in its herd, which was in agreement with the epidemiology of the AS/Nor98 [1,19,20].

The majority of PrP genotypes described herein were observed in other AS/Nor98 cases [36]. We found an over-representation of animals carrying AF141RQ and AL141RQ alleles, suggesting that these alleles may confer more susceptibility to atypical scrapie in Latxa breed sheep. We also described a novel genotype associated to AS that has not been previously described (AL141RQ/AL141RH).

Case reports from this study and other case reports from Spain (http://www.eeb.es/pags/espana.htm) and Portugal [35], indicate a high frequency of atypical cases compared to CS outbreaks in the Iberian Peninsula. It could be speculated that AS/Nor98 is the traditional form of scrapie in the Iberian part of the Basque country, whilst in the French part, the classical form has been predominant [59]. This

12

would point to some unidentified epidemiological features limiting the spread of classical scrapie in the Iberian Peninsula. However, since the analysis of all sheep can not be guaranteed, it is difficult to test this hypothesis. The analysis of all sheep would provide more information about the epidemiology and pathology of this disease. Moreover, it could contribute in assessing whether AS is present in the Basque Country with the same high frequencies as others human TSEs, such as sporadic Creutzfeldt- Jakob disease [60] and Fatal Familiar Insomnia compared to other Spanish autonomous communities (National Epidemiology Centre:





http://www.isciii.es/htdocs/centros/epidemiologia/epidemiologia_listado_ecj.jsp).



Conclusions

This work indicates that AS/Nor98 constitutes the most common small ruminant Transmissible Spongiform Encephalopathy form in the Latxa breed in the Spanish Basque Country, where it also affects a genotype (ALRQ/ALRH) not previously associated to this form of TSE.


SNIP....SEE FULL TEXT ;


Atypical/Nor98 scrapie in the Basque Country: a case report of eight outbreaks BMC Veterinary Research 2010, 6:17 doi:10.1186/1746-6148-6-17




http://www.biomedcentral.com/content/pdf/1746-6148-6-17.pdf




TSS

Wednesday, March 3, 2010

NOR-98 ATYPICAL SCRAPIE USA 4 CASES DETECTED JANUARY 2010

Greetings,

Unusual event if you consider the officials hypothisis that Nor-98 atypical scrapie is a spontaneous event. seems there was a great deal of spontaneous mutations for this time period ;-)...TSS


http://nor-98.blogspot.com/2010/03/nor-98-atypical-scrapie-usa-4-cases.html



Thursday, March 11, 2010

CANADA TYPICAL AND ATYPICAL SCRAPIE REPORT TO MARCH 2010


http://nor-98.blogspot.com/2010/03/canada-typical-and-atypical-scrapie.html



Monday, November 30, 2009

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


http://nor-98.blogspot.com/2009/11/usda-and-oie-collaborate-to-exclude.html



Monday, December 14, 2009

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

hmmm, this is getting interesting now...

Sporadic CJD type 1 and atypical/ Nor98 scrapie are characterized by fine (reticular) deposits,

see also ;

All of the Heidenhain variants were of the methionine/ methionine type 1 molecular subtype.


http://cjdusa.blogspot.com/2009/09/co-existence-of-scrapie-prion-protein.html



see full text ;

Monday, December 14, 2009

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


http://nor-98.blogspot.com/2009/12/similarities-between-forms-of-sheep.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

SCRAPIE, ATYPICAL, OVINE - AUSTRALIA: (WESTERN AUSTRALIA) SUSPECTED ******************************************************************* A ProMED-mail post ProMED-mail is a program of the International Society for Infectious Diseases

[1] Date: Fri 12 Mar 2010

Source: The Australian [edited]



A West Australian sheep has been found to have signs characteristic of the fatal brain disease atypical scrapie. It comes as Australia faces growing anger from its trade partners over the Rudd government's surprise decision to extend a ban on the importation of beef from countries exposed to mad cow disease for a further 2 years.

Australia's chief veterinarian, Andy Carroll, told the ABC an indicative case of the atypical scrapie had been confirmed but said it posed no risk to human or animal health or the safety of eating meat and animal products.

Nor does atypical scrapie carry the dire trade consequences associated with classical scrapie.

Classical scrapie is in the same transmissible spongiform encephalopathies (TSE) family as BSE, better known as mad cow disease, from which humans can be fatally infected.

Dr Carroll said samples from the sheep's brain were being sent to the World Reference Laboratory in Britain.

Neither atypical scrapie nor classical scrapie has been seen in Australia before, but a sheep in New Zealand tested positive to the atypical form last year [2009].

Atypical scrapie is a relatively recently discovered disease and the common scientific view is that it occurs spontaneously or naturally in very small numbers of older sheep in countries all over the world.

[Byline: Jodie Minus]

-- Communicated by: Sabine Zentis Castleview Pedigree English Longhorns Gut Laach 52385 Nideggen Germany

****** [2] Date: Wed 10 Mar 2010 Source: ABC News (Australian Broadcasting Corporation) [edited]

Animal health authorities are testing a sheep's brain for what could be Australia's 1st case of the disease atypical scrapie.

Although not confirmed, the sheep is thought to be from Western Australia.

This type of scrapie is described as a sporadic degenerative brain condition affecting older sheep, and is not contagious.

Ed Klim, from national advisory group SafeMeat, says a 2nd round of testing is now taking place. "We've been made aware that the Australian Animal Health Laboratory is conducting further routine testing on a sheep sample," he says.

"The disease isn't considered a health risk nor should have any impact on food safety or export markets for sheep meat of live sheep."

Australia's chief veterinarian and WA's Department of Agriculture of Food are both aware of the testing but will not comment.

-- Communicated by: Terry S Singeltary Sr

[Although atypical scrapie is not yet ruled out, it is important to realize this is a type of scrapie that thus far has only tended to appear as a sporadic condition in older animals. Currently it has not been shown to follow the same genetic tendencies for propagation as the usual scrapie.

However, the atypical phenotypic appearance has been shown to be preserved on experimental passage.

Atypical scrapie was first identified in Norwegian sheep in 1998 and has subsequently been identified in many countries, as Australia may join that list. It is likely that this case will be sent to the UK for definitive conformation.

[Ref: M Simmons, T Konold, L Thurston, et al. BMC Veterinary Research 2010, 6:14 [provisional abstract available at ]

"Background ----------- "Retrospective studies have identified cases predating the initial identification of this form of scrapie, and epidemiological studies have indicated that it does not conform to the behaviour of an infectious disease, giving rise to the hypothesis that it represents spontaneous disease. However, atypical scrapie isolates have been shown to be infectious experimentally, through intracerebral inoculation in transgenic mice and sheep. [Many of the neurological diseases can be transmitted by intracerebral inoculation, which causes this moderator to approach intracerebral studies as a tool for study, but not necessarily as a direct indication of transmissibility of natural diseases. - Mod.TG]

"The 1st successful challenge of a sheep with 'field' atypical scrapie from an homologous donor sheep was reported in 2007.

"Results -------- "This study demonstrates that atypical scrapie has distinct clinical, pathological, and biochemical characteristics which are maintained on transmission and sub-passage, and which are distinct from other strains of transmissible spongiform encephalopathies in the same host genotype.

"Conclusions ------------ Atypical scrapie is consistently transmissible within AHQ homozygous sheep, and the disease phenotype is preserved on sub-passage."

Lastly, this moderator wishes to thank Terry Singletary for some of his behind the scenes work of providing citations and references for this posting. - Mod.TG]

The HealthMap/ProMED-mail interactive map of Australia is available at . - Sr.Tech.Ed.MJ]

[see also: 2009 ---- Scrapie, atypical, ovine - New Zealand (02) 20091029.3740 Scrapie, atypical, ovine - New Zealand 20090220.0714 2007 ---- Scrapie, atypical, sheep - USA (WY): 1st report 20070318.0949 2005 ---- Scrapie, atypical, ovine - Falkland Islands 20051120.3371 2004 ---- Scrapie, atypical, sheep - UK and Ireland 20041210.3274 Scrapie, atypical, sheep - UK (02) 20040409.0965 Scrapie, atypical, sheep - UK 20040408.0952 Scrapie, atypical, sheep - France: OIE 20040201.0390] ...................................sb/tg/mj/lm

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http://www.promedmail.org/pls/apex/f?p=2400:1001:3033292671016132::NO::F2400_P1001_BACK_PAGE,F2400_P1001_PUB_MAIL_ID:1010,81729






Thursday, March 18, 2010

The natural atypical scrapie phenotype is preserved on experimental transmission and sub-passage in PRNP homologous sheep



http://nor-98.blogspot.com/2010/03/natural-atypical-scrapie-phenotype-is.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.

snip...

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

PMID: 6997404


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


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



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

Transmission of scrapie to the cynomolgus monkey (Macaca fascicularis). Gibbs CJ Jr, Gajdusek DC.

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

Transmission of Scrapie to the Cynomolgus Monkey (Macaca fascicularis)

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

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

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


http://www.nature.com/nature/journal/v236/n5341/abs/236073a0.html



EMBO reports 4, 5, 530–533 (2003) doi:10.1038/sj.embor.embor827 AOP Published online: 11 April 2003

Widespread PrPSc accumulation in muscles of hamsters orally infected with scrapie

Achim Thomzig, Christine Kratzel, Gudrun Lenz, Dominique Krüger & Michael Beekes

Robert Koch-Institut, P26, Nordufer 20, D-13353 Berlin, Germany

To whom correspondence should be addressed Michael Beekes Tel: +49 30 4547 2396; Fax: +49 30 4547 2609; BeekesM@rki.de

Received 13 February 2003; Accepted 13 March 2003; Published online 11 April 2003.

Abstract

Scrapie, bovine spongiform encephalopathy and chronic wasting disease are orally communicable, transmissible spongiform encephalopathies (TSEs). As zoonotic transmissions of TSE agents may pose a risk to human health, the identification of reservoirs for infectivity in animal tissues and their exclusion from human consumption has become a matter of great importance for consumer protection. In this study, a variety of muscles from hamsters that were orally challenged with scrapie was screened for the presence of a molecular marker for TSE infection, PrPSc (the pathological isoform of the prion protein PrP). Sensitive western blotting revealed consistent PrPSc accumulation in skeletal muscles from forelimb and hindlimb, head, back and shoulder, and in tongue. Previously, our animal model has provided substantial baseline information about the peripheral routing of infection in naturally occurring and orally acquired ruminant TSEs. Therefore, the findings described here highlight further the necessity to investigate thoroughly whether muscles of TSE-infected sheep, cattle, elk and deer contain infectious agents.

EMBO reports 4, 5, 530–533 (2003) doi:10.1038/sj.embor.embor827 AOP Published online: 11 April 2003



http://www.nature.com/embor/journal/v4/n5/full/embor827.html





EVIDENCE OF SCRAPIE IN SHEEP AS A RESULT OF FOOD BORNE EXPOSURE

This is provided by the statistically significant increase in the incidence of sheep scrape from 1985, as determined from analyses of the submissions made to VI Centres, and from individual case and flock incident studies. ........



http://web.archive.org/web/20030517224223/http://www.bseinquiry.gov.uk/files/yb/1994/02/07002001.pdf


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