CANADA TYPICAL AND ATYPICAL SCRAPIE REPORT TO MARCH 2010
Flocks infected with scrapie in Canada in 2010 The CFIA, in co-operation with provincial governments and industry, launched a national scrapie surveillance program in 2005. Under the program, producers are encouraged to report animals that die on the farm or exhibit symptoms of the disease.
In addition, scrapie is a reportable disease under the Health of Animals Regulations. This means that all suspected cases must be reported to the CFIA.
The following table lists sheep flocks and/or goat herds confirmed to be infected with scrapie in Canada in 2010.
Updated: 2010-02-28
Date confirmed Location Animal type infected
January 21 Alberta Sheep
January 25* Ontario Sheep
February 5 Quebec Sheep
February 5* Saskatchewan Sheep
*Atypical scrapie
http://www.inspection.gc.ca/english/anima/disemala/rep/2010scrtree.shtml
BSE, BOVINE - CANADA: (ALBERTA) ******************************* A
ProMED-mail post
http://www.promedmail.org/pls/apex/f?p=2400:1001:2081979993451657::NO::F2400_P1001_BACK_PAGE,F2400_P1001_PUB_MAIL_ID:1000,81711
Canada - Case of BSE (Mad cow disease) in 6 year old cow 17th domestic case
http://bseusa.blogspot.com/2010/03/canada-case-of-bse-mad-cow-disease-in-6.html
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
Terry S. Singeltary Sr.
P.O. Box 42
Bacliff, Texas USA 77518
Showing posts with label scrapie. Show all posts
Showing posts with label scrapie. Show all posts
Thursday, March 11, 2010
Wednesday, March 3, 2010
NOR-98 ATYPICAL SCRAPIE USA 4 CASES DETECTED JANUARY 2010
Scrapie Flock Certification Program
As of January 31, 2010, there were 1,701 flocks participating in the Scrapie Flock Certification Program (SFCP). Of these flocks, 1,094 were complete monitored flocks, 551 were certified, 51 were export monitored, and 5 were selective monitored flocks (Figures 1 and la). Six flocks were enrolled or certified during January (Figure 2). SFCP open statuses by fiscal year from FY 1997 to FY 2010 are depicted in Chart 1.
Infected and Source Flocks
As of January 31, 2010, there were 11 scrapie infected and source flocks with open statuses (Figure 3). There were no flocks designated as infected or source in January. In FY 2010, two new infected flocks and two new source flocks were reported (Figure 4); eight flocks completed a clean-up plan and were released (Figure 5). The ratio of infected and source flocks released to newly identified infected and source flocks for FY 2010 = 2 : 1. New infected and source statuses from FY 1997 to FY 2010 are depicted in Chart 2.
Positive Scrapie Cases
As of January 31, 2010, 24 positive cases in sheep or goats were reported by the National Veterinary Services Laboratories (NVSL); 14 were field cases and 10 were Regulatory Scrapie Slaughter Surveillance (RSSS) cases collected between October 1,2009 and January 31,2010 and confirmed by February 19,2010 (Figure 6). Three RSSS cases and one field case were diagnosed as Nor98-like scrapie. Field cases are positive animals tested as part of a disease investigation including potentially exposed, exposed, and suspect animals. Twenty one cases of scrapie in goats have been confirmed by NVSL since implementation of the regulatory changes in FY 2002 (Figure 7). 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 has been held in quarantine for research by USDA's Agricultural Research Service since 2008.
Regulatory Scrapie Slaughter Surveillance (RSSS)
RSSS started April 1, 2003. It is a targeted slaughter surveillance program which is designed to identify infected flocks. Samples have been collected from 246,453 animals since April 1, 2003. There have been 431 NVSL confirmed positive animals since the beginning ofRSSS. As of January 31, 2010, 15,184 samples have been collected in FY 2010. Seven samples collected in FY 2010 have tested positive for classical scrapie"; the face colors of the positive sheep were 5 black-face and 2 mottled-face. Three samples (2 mottled-face and 1 white-face sheep) tested positive for Nor98-like scrapie. The percent of samples that have tested positive for each face color from FY 2003 through 2010 is depicted in Chart 3. Cumulative regional sample collection numbers are shown in Chart 4 and are based upon the state in which the animal was tagged. The number ofRSSS animals collected for FY 2010 by month and by region where collected is shown in Chart 5. A monthly comparison ofRSSS collections by fiscal year is displayed in Chart 6. A retrospective 6 month rolling average of the percent positive, black-faced sheep sampled at RSSS collections sites is shown in Chart 7.
*RSSS positives are reported based on collection date and may have been confirmed after January 31,2010.
Animals Sampled for Scrapie Testing
As of January 31, 2010,15,693 animals have been sampled for scrapie testing: 15,184 RSSS samples, 428 regulatory field cases, and 81 live-animal biopsies (Chart 8).
This report is based on information and test results available at the time of report generation. Numbers are subject to change due to later reporting of test results and updates in the database.
http://www.aphis.usda.gov/animal_health/animal_diseases/scrapie/downloads/monthly_scrapie_rpt.pps
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
Atypical Nor-98 states in this report for January 2010 include ; Maine, Pennsylvania, Ohio, and Oregon
kind regards, terry
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
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
Tuesday, April 28, 2009
Nor98-like Scrapie in the United States of America
http://nor-98.blogspot.com/2009/04/nor98-like-scrapie-in-united-states-of.html
P03.141
Aspects of the Cerebellar Neuropathology in Nor98
Gavier-Widén, D1; Benestad, SL2; Ottander, L1; Westergren, E1 1National Veterinary Insitute, Sweden; 2National Veterinary Institute,
Norway Nor98 is a prion disease of old sheep and goats. This atypical form of scrapie was first described in Norway in 1998. Several features of Nor98 were shown to be different from classical scrapie including the distribution of disease associated prion protein (PrPd) accumulation in the brain. The cerebellum is generally the most affected brain area in Nor98. The study here presented aimed at adding information on the neuropathology in the cerebellum of Nor98 naturally affected sheep of various genotypes in Sweden and Norway. A panel of histochemical and immunohistochemical (IHC) stainings such as IHC for PrPd, synaptophysin, glial fibrillary acidic protein, amyloid, and cell markers for phagocytic cells were conducted. The type of histological lesions and tissue reactions were evaluated. The types of PrPd deposition were characterized. The cerebellar cortex was regularly affected, even though there was a variation in the severity of the lesions from case to case. Neuropil vacuolation was more marked in the molecular layer, but affected also the granular cell layer. There was a loss of granule cells. Punctate deposition of PrPd was characteristic. It was morphologically and in distribution identical with that of synaptophysin, suggesting that PrPd accumulates in the synaptic structures. PrPd was also observed in the granule cell layer and in the white matter. The pathology features of Nor98 in the cerebellum of the affected sheep showed similarities with those of sporadic Creutzfeldt-Jakob disease in humans.
***The pathology features of Nor98 in the cerebellum of the affected sheep showed similarities with those of sporadic Creutzfeldt-Jakob disease in humans.
http://www.prion2007.com/pdf/Prion%20Book%20of%20Abstracts.pdf
PR-26
NOR98 SHOWS MOLECULAR FEATURES REMINISCENT OF GSS
R. Nonno1, E. Esposito1, G. Vaccari1, E. Bandino2, M. Conte1, B. Chiappini1, S. Marcon1, M. Di Bari1, S.L. Benestad3, U. Agrimi1 1 Istituto Superiore di Sanità, Department of Food Safety and Veterinary Public Health, Rome, Italy (romolo.nonno@iss.it); 2 Istituto Zooprofilattico della Sardegna, Sassari, Italy; 3 National Veterinary Institute, Department of Pathology, Oslo, Norway
Molecular variants of PrPSc are being increasingly investigated in sheep scrapie and are generally referred to as "atypical" scrapie, as opposed to "classical scrapie". Among the atypical group, Nor98 seems to be the best identified. We studied the molecular properties of Italian and Norwegian Nor98 samples by WB analysis of brain homogenates, either untreated, digested with different concentrations of proteinase K, or subjected to enzymatic deglycosylation. The identity of PrP fragments was inferred by means of antibodies spanning the full PrP sequence. We found that undigested brain homogenates contain a Nor98-specific PrP fragment migrating at 11 kDa (PrP11), truncated at both the C-terminus and the N-terminus, and not N-glycosylated. After mild PK digestion, Nor98 displayed full-length PrP (FL-PrP) and N-glycosylated C-terminal fragments (CTF), along with increased levels of PrP11. Proteinase K digestion curves (0,006-6,4 mg/ml) showed that FL-PrP and CTF are mainly digested above 0,01 mg/ml, while PrP11 is not entirely digested even at the highest concentrations, similarly to PrP27-30 associated with classical scrapie. Above 0,2 mg/ml PK, most Nor98 samples showed only PrP11 and a fragment of 17 kDa with the same properties of PrP11, that was tentatively identified as a dimer of PrP11. Detergent solubility studies showed that PrP11 is insoluble in 2% sodium laurylsorcosine and is mainly produced from detergentsoluble, full-length PrPSc. Furthermore, among Italian scrapie isolates, we found that a sample with molecular and pathological properties consistent with Nor98 showed plaque-like deposits of PrPSc in the thalamus when the brain was analysed by PrPSc immunohistochemistry. Taken together, our results show that the distinctive pathological feature of Nor98 is a PrP fragment spanning amino acids ~ 90-155. This fragment is produced by successive N-terminal and C-terminal cleavages from a full-length and largely detergent-soluble PrPSc, is produced in vivo and is extremely resistant to PK digestion.
*** Intriguingly, these conclusions suggest that some pathological features of Nor98 are reminiscent of Gerstmann-Sträussler-Scheinker disease.
119
http://www.neuroprion.com/pdf_docs/conferences/prion2006/abstract_book.pdf
A newly identified type of scrapie agent can naturally infect sheep with resistant PrP genotypes
Annick Le Dur*,?, Vincent Béringue*,?, Olivier Andréoletti?, Fabienne Reine*, Thanh Lan Laï*, Thierry Baron§, Bjørn Bratberg¶, Jean-Luc Vilotte?, Pierre Sarradin**, Sylvie L. Benestad¶, and Hubert Laude*,?? +Author Affiliations
*Virologie Immunologie Moléculaires and ?Génétique Biochimique et Cytogénétique, Institut National de la Recherche Agronomique, 78350 Jouy-en-Josas, France; ?Unité Mixte de Recherche, Institut National de la Recherche Agronomique-Ecole Nationale Vétérinaire de Toulouse, Interactions Hôte Agent Pathogène, 31066 Toulouse, France; §Agence Française de Sécurité Sanitaire des Aliments, Unité Agents Transmissibles Non Conventionnels, 69364 Lyon, France; **Pathologie Infectieuse et Immunologie, Institut National de la Recherche Agronomique, 37380 Nouzilly, France; and ¶Department of Pathology, National Veterinary Institute, 0033 Oslo, Norway
Edited by Stanley B. Prusiner, University of California, San Francisco, CA (received for review March 21, 2005)
Abstract Scrapie in small ruminants belongs to transmissible spongiform encephalopathies (TSEs), or prion diseases, a family of fatal neurodegenerative disorders that affect humans and animals and can transmit within and between species by ingestion or inoculation. Conversion of the host-encoded prion protein (PrP), normal cellular PrP (PrPc), into a misfolded form, abnormal PrP (PrPSc), plays a key role in TSE transmission and pathogenesis. The intensified surveillance of scrapie in the European Union, together with the improvement of PrPSc detection techniques, has led to the discovery of a growing number of so-called atypical scrapie cases. These include clinical Nor98 cases first identified in Norwegian sheep on the basis of unusual pathological and PrPSc molecular features and "cases" that produced discordant responses in the rapid tests currently applied to the large-scale random screening of slaughtered or fallen animals. Worryingly, a substantial proportion of such cases involved sheep with PrP genotypes known until now to confer natural resistance to conventional scrapie. Here we report that both Nor98 and discordant cases, including three sheep homozygous for the resistant PrPARR allele (A136R154R171), efficiently transmitted the disease to transgenic mice expressing ovine PrP, and that they shared unique biological and biochemical features upon propagation in mice. These observations support the view that a truly infectious TSE agent, unrecognized until recently, infects sheep and goat flocks and may have important implications in terms of scrapie control and public health.
http://www.pnas.org/content/102/44/16031.abstract
Monday, December 1, 2008 When Atypical Scrapie cross species barriers
Authors
Andreoletti O., Herva M. H., Cassard H., Espinosa J. C., Lacroux C., Simon S., Padilla D., Benestad S. L., Lantier F., Schelcher F., Grassi J., Torres, J. M., UMR INRA ENVT 1225, Ecole Nationale Veterinaire de Toulouse.France; ICISA-INlA, Madrid, Spain; CEA, IBiTec-5, DSV, CEA/Saclay, Gif sur Yvette cedex, France; National Veterinary Institute, Postboks 750 Sentrum, 0106 Oslo, Norway, INRA IASP, Centre INRA de Tours, 3738O Nouzilly, France.
Content
Atypical scrapie is a TSE occurring in small ruminants and harbouring peculiar clinical, epidemiological and biochemical properties. Currently this form of disease is identified in a large number of countries. In this study we report the transmission of an atypical scrapie isolate through different species barriers as modeled by transgenic mice (Tg) expressing different species PRP sequence.
The donor isolate was collected in 1995 in a French commercial sheep flock. inoculation into AHQ/AHQ sheep induced a disease which had all neuro-pathological and biochemical characteristics of atypical scrapie. Transmitted into Transgenic mice expressing either ovine or PrPc, the isolate retained all the described characteristics of atypical scrapie.
Surprisingly the TSE agent characteristics were dramatically different v/hen passaged into Tg bovine mice. The recovered TSE agent had biological and biochemical characteristics similar to those of atypical BSE L in the same mouse model. Moreover, whereas no other TSE agent than BSE were shown to transmit into Tg porcine mice, atypical scrapie was able to develop into this model, albeit with low attack rate on first passage.
Furthermore, after adaptation in the porcine mouse model this prion showed similar biological and biochemical characteristics than BSE adapted to this porcine mouse model. Altogether these data indicate.
(i) the unsuspected potential abilities of atypical scrapie to cross species barriers
(ii) the possible capacity of this agent to acquire new characteristics when crossing species barrier
These findings raise some interrogation on the concept of TSE strain and on the origin of the diversity of the TSE agents and could have consequences on field TSE control measures.
http://www.neuroprion.org/resources/pdf_docs/conferences/prion2008/abstract-book-prion2008.pdf
NOR-98 ATYPICAL SCRAPIE 5 cases documented in USA in 5 different states USA 2007
http://nor-98.blogspot.com/2008/04/seac-spongiform-encephalopathy-advisory.html
Tuesday, June 3, 2008
SCRAPIE USA UPDATE JUNE 2008 NOR-98 REPORTED PA
http://nor-98.blogspot.com/2008/06/scrapie-usa-update-june-2008-nor-98.html
http://nor-98.blogspot.com/
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
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
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://www.bseinquiry.gov.uk/files/yb/1994/02/07002001.pdf
NEW URL BELOW ;
http://web.archive.org/web/20030517224223/http://www.bseinquiry.gov.uk/files/yb/1994/02/07002001.pdf
Rangen Inc 2/11/10
Department of Health and Human Services Public Health Service Food and Drug Administration Seattle District Pacific Region 22201 23rd Drive SE Bothell, WA 98021-4421 Telephone: 425-486-8788 FAX: 425-483-4996
February 11, 2010
CERTIFIED MAIL
RETURN RECEIPT REQUESTED
In reply refer to Warning Letter SEA 10-11
Christopher T. Rangen, President Rangen, Inc. 115-13th Avenue South PO Box 706 Buhl, Idaho 83316
WARNING LETTER
Dear Mr. Rangen: On June 9-11, 2009, U.S. Food and Drug Administration (FDA) investigators inspected your animal feed manufacturing facilities located at 115-13th Avenue South, Buhl, Idaho. The inspection revealed significant deviations from the requirements set forth in Title 21, Code of Federal Regulations, Section 589.2000 (21 C.F.R. 589.2000), Animal Proteins Prohibited in Ruminant Feed. This regulation is intended to prevent the establishment and amplification of Bovine Spongiform Encephalopathy (BSE). You failed to follow the requirements of this regulation, resulting in products being manufactured and distributed by your facility that were adulterated within the meaning of section 402(a)(4) of the Federal Food, Drug, and Cosmetic Act (the Act), 21 U.S.C. § 342(a)(4), and misbranded within the meaning of section 403(a)(1) of the Act, 21 U.S.C. § 343(a)(1). Our investigation determined that adulteration resulted from the failure of your firm to provide for measures to avoid commingling or cross-contamination. The adulterated feed was subsequently misbranded because it was not properly labeled. Specifically, we found:
1. Your firm failed to provide for and use cleanout procedures or other means adequate to prevent carry-over of products that contain or may contain proteins derived from mammalian tissues into animal feed that may be used for ruminants, as required by 21 CFR 589.2000(e)(1)(iii)(B). Since your feed is prepared, packed, or held under these conditions it is, therefore, adulterated under section 402(a)(4) of the Act, 21 U.S.C. § 342(a)(4).
. Mink feed that was not labeled "Do not feed to cattle or other ruminants," in accordance with 21 CFR 589.2000(e)(1)(i) and that, therefore, might be fed to ruminants, was produced using the same equipment as aquaculture feed that contains proteins derived from mammalian tissues, such as meat and bone meal. You conducted no clean-outs or flushes of equipment to remove proteins derived from mammalian tissues that may have been present before manufacturing the mink feed that might be fed to ruminants.
. The auger trucks you used to deliver bulk mink feed which contained or may have contained proteins derived from mammalian tissues were not subject to an effective clean-out prior to their use to deliver bulk animal feed, including ruminant feed, that did not contain such materials. There were no procedures to clean the trucks to remove proteins derived from mammalian tissues before shipment of animal feeds that did not contain such materials.
2. You failed to label all products which contained or may have contained proteins derived from mammalian tissues with the statement, "Do not feed to cattle or other ruminants," as required by 21 C.F.R. 589.2000(e)(1)(i). Such products are misbranded under Section 403(a)(1) of the Act, 21 U.S.C. § 343(a)(1). The misbranded product includes bulk mink feed.
. On June 9, 2009, the investigators observed approximately (b)(4) pallets of (b)(4) 50 pound bags of (b)(4) MINK FEED, lot 06/05/09. All bagged mink feed, as well as approximately (b)(4)% of bulk mink feed, manufactured at your facility, was produced using the aquaculture feed production equipment used to produce feed containing proteins derived from mammalian tissues. Because mink feed produced using this equipment may have contained mammalian tissues, it was not properly labeled, as required by 21 C.F.R. 589.2000(e)(1)(i).
This letter is not intended to serve as an all-inclusive list of violations at your facility. As a manufacturer of materials intended for animal feed use, you are responsible for ensuring your overall operation and the products you manufacture and distribute are in compliance with the law. You should take prompt action to correct the above violations and you should establish a system whereby violations do not occur. Failure to promptly correct these violations may result in regulatory action, such seizure and/or injunction, without further notice.
We acknowledge your July 31, 2009 letter detailing procedures you had implemented or planned to implement to prevent future violations of FDA regulations relating to mammalian proteins in animal feed. In particular the letter stated that Rangen would no longer purchase meat and bone meal for use in any of its animal feeds and that existing inventories of mammalian protein ingredients would be exhausted by December 31, 2009. Division Manager, Joy Kinyon made similar assertions in the course of FDA's June 2009 inspection. The July 31, 2009 letter further set out procedures Rangen would use to remedy observed violations of FDA regulations while mammalian proteins were still being used at Rangen. Finally you explained steps taken to recover or relabel feed that may have been contaminated due to commingling resulting from your manufacturing and distribution procedures. Within fifteen (15) working days of receiving this letter you should, in writing, confirm the steps you took prior to receiving this letter and notify FDA of steps you have taken since receiving this letter to bring your firm into compliance with the law. Your response should include each step that has been taken or will be taken to correct the violations and prevent their recurrence. If corrective action cannot be completed within fifteen (15) working days, state the reason for the delay and the time frame within which the corrections will be completed. Please include copies of any available documentation demonstrating that corrections have been made.
Your written reply should be directed to Scott A. Nabe, Compliance Officer, U.S. Food and Drug Administration, 22201 23rd Drive SE, Bothell, Washington 98021-4421. If you have any questions about this letter, please contact Mr. Nabe at (425) 483-4753.
Sincerely,
/s/
Charles M. Breen District Director Seattle District
cc: Joy A. Kinyon, Division Manager, Aquaculture Feeds-General Feeds Rangen, Inc. PO Box 706 115-13th Avenue South Buhl, Idaho 83316
http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/ucm201893.htm
Monday, March 1, 2010
ANIMAL PROTEIN I.E. MAD COW FEED IN COMMERCE A REVIEW 2010
http://madcowfeed.blogspot.com/2010/03/animal-protien-ie-mad-cow-feed-in.html
Tuesday, March 2, 2010
Animal Proteins Prohibited in Ruminant Feed/Adulterated/Misbranded Rangen Inc 2/11/10 USA
http://madcowfeed.blogspot.com/2010/03/animal-proteins-prohibited-in-ruminant.html
. Mink feed that was not labeled "Do not feed to cattle or other ruminants," in accordance with 21 CFR 589.2000(e)(1)(i) and that, therefore, might be fed to ruminants, was produced using the same equipment as aquaculture feed that contains proteins derived from mammalian tissues, such as meat and bone meal. You conducted no clean-outs or flushes of equipment to remove proteins derived from mammalian tissues that may have been present before manufacturing the mink feed that might be fed to ruminants.
<<< href="http://www.cdc.gov/eid/content/13/12/1887.htm?s_cid=eid1887_e">http://www.cdc.gov/eid/content/13/12/1887.htm?s_cid=eid1887_e
Over the next 8-10 weeks, approximately 40% of all the adult mink on the farm died from TME.
snip...
The rancher was a ''dead stock'' feeder using mostly (>95%) downer or dead dairy cattle...
http://web.archive.org/web/20030516051623/http://www.bseinquiry.gov.uk/files/mb/m09/tab05.pdf
An update on atypical BSE and other TSE in North America. Please remember, the typical U.K. c-BSE, the atypical l-BSE (BASE), and h-BSE have all been documented in North America, along with the typical scrapie's, and atypical Nor-98 Scrapie, and to date, 2 different strains of CWD, and also TME. All these TSE in different species have been rendered and fed to food producing animals for humans and animals in North America (TSE in cats and dogs ?), and that the trading of these TSEs via animals and products via the USA and Canada has been immense over the years, decades.
SEE PAGE 114 ;
http://ww2.isid.org/Downloads/14th_ICID_ISE_Abstracts.pdf
http://transmissiblespongiformencephalopathy.blogspot.com/
LIKE i said before, the OIE not only sold their soul to the devil over the BSE MRR, they sold yours too ;
Wednesday, February 10, 2010
NAIS MAD COW TRACEABILITY DUMPED BY USDA APHIS 2010
http://naiscoolyes.blogspot.com/2010/02/nais-mad-cow-traceability-dumped-by.html
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
Scientific Report of the European Food Safety Authority on the Assessment of the Geographical BSE Risk (GBR) of the USA Question number: EFSA-Q-2003-083
Adopted: 1 July 2004 Summary (0.1Mb)
Report (0.2Mb)
Summary
The European Food Safety Authority and its Scientific Expert Working Group on the Assessment of the Geographical Bovine Spongiform Encephalopathy (BSE) Risk (GBR) were asked by the European Commission (EC) to provide an up-to-date scientific report on the GBR in the United States of America, i.e. the likelihood of the presence of one or more cattle being infected with BSE, pre-clinically as well as clinically, in USA. This scientific report addresses the GBR of USA as assessed in 2004 based on data covering the period 1980-2003.
The BSE agent was probably imported into USA and could have reached domestic cattle in the middle of the eighties. These cattle imported in the mid eighties could have been rendered in the late eighties and therefore led to an internal challenge in the early nineties. It is possible that imported meat and bone meal (MBM) into the USA reached domestic cattle and leads to an internal challenge in the early nineties.
A processing risk developed in the late 80s/early 90s when cattle imports from BSE risk countries were slaughtered or died and were processed (partly) into feed, together with some imports of MBM. This risk continued to exist, and grew significantly in the mid 90’s when domestic cattle, infected by imported MBM, reached processing. Given the low stability of the system, the risk increased over the years with continued imports of cattle and MBM from BSE risk countries.
EFSA concludes that the current GBR level of USA is III, i.e. it is likely but not confirmed that domestic cattle are (clinically or pre-clinically) infected with the BSE-agent. As long as there are no significant changes in rendering or feeding, the stability remains extremely/very unstable. Thus, the probability of cattle to be (pre-clinically or clinically) infected with the BSE-agent persistently increases.
http://www.efsa.europa.eu/EFSA/efsa_locale-1178620753812_1211902594180.htm
Monday, November 23, 2009
BSE GBR RISK ASSESSMENTS UPDATE NOVEMBER 23, 2009 COMMISSION OF THE EUROPEAN COMMUNITIES AND O.I.E.
http://docket-aphis-2006-0041.blogspot.com/2009/11/bse-gbr-risk-assessments-update.html
Greetings,
HAVE we come to a point to where sub-clinical disease is an acceptable factor ???
LEGALLY, is it o.k. to be sub-clinically infected from a contaminated product ???
IF SO, what is the legality from the second passage infection from that sub-clinical host to clinical infection via the pass it forward and or friendly fire mode of transmission for any iatrogenic Transmissible Spongiform encephalopathy to second, third, fourth passage ???
CJD USA RISING, with UNKNOWN PHENOTYPE ;
5 Includes 41 cases in which the diagnosis is pending, and 17 inconclusive cases; 6 Includes 46 cases with type determination pending in which the diagnosis of vCJD has been excluded.
http://www.cjdsurveillance.com/pdf/case-table.pdf
WHY DO FARMERS AND THEIR WIVES WITH BSE HERDS, ONLY HAVE SPORADIC CJD ???
Monday, May 19, 2008
SPORADIC CJD IN FARMERS, FARMERS WIVES, FROM FARMS WITH BSE HERD AND ABATTOIRS
http://bseinquiry.blogspot.com/
Sunday, August 10, 2008
A New Prionopathy OR more of the same old BSe and sporadic CJD
http://creutzfeldt-jakob-disease.blogspot.com/2008/08/new-prionopathy-or-more-of-same-old-bse.html
full text ;
Saturday, February 27, 2010
SEAC Agenda 104th meeting on Friday 5th March 2010
http://seac992007.blogspot.com/2010/02/seac-agenda-104th-meeting-on-friday-5th.html
Saturday, February 27, 2010
FINAL REPORT OF THE TESTING OF THE BELGIAN (VERMONT) SHEEP February 27, 2010
http://foiamadsheepmadrivervalley.blogspot.com/2010/02/final-report-of-testing-of-belgian.html
Prions: Protein Aggregation and Infectious Diseases
ADRIANO AGUZZI AND ANNA MARIA CALELLA
Institute of Neuropathology, University Hospital of Zurich, Zurich, Switzerland
snip...
3. Sporadic Creutzfeldt-Jakob disease Approximately 85% of all human prion diseases are sporadic forms of CJD. For sCJD, there is no association with a mutant PRNP allele, nor is there any epidemiological evidence for exposure to a TSE agent through contact with people or animals infected with TSEs. sCJD cases are currently subclassified according to the methionine/valine polymorphism at codon 129 of the PRNP gene and the size and glycoform ratio of proteaseresistant prion protein identified on western blot (type 1 or type 2) (174). Heterozygosity (Met/Val) at PrP codon 129 appears to be associated with a lower risk (378) and/or prolonged incubation time (119, 387). The lack of routine laboratory testing for preclinical diagnosis makes the search for agent sources and other risk factors extremely difficult. At present, the means of acquisition of a TSE agent in these patients remains a mystery. So far, there is no evidence for spontaneous PrPSc formation in any animal or human TSE. In humans, the peak age incidence of sporadic CJD is 55–60 years. However, if spontaneous misfolding were the primary event, one might expect a continuously increasing incidence with age because more time would allow more opportunity for rare misfolding events.
snip...
Physiol Rev • VOL 89 • OCTOBER 2009 • www.prv.org
http://physrev.physiology.org/cgi/content/abstract/89/4/1105
Science 24 September 2004: Vol. 305. no. 5692, pp. 1918 - 1921 DOI: 10.1126/science.1103581
Perspectives BIOMEDICINE:
A Fresh Look at BSE
Bruce Chesebro*
snip...
BSE caused by spontaneous misfolding of the prion protein has not been proven.
snip...
What can we conclude so far about BSE in North America? Is the BSE detected in two North American cows sporadic or spontaneous or both? "Sporadic" pertains to the rarity of disease occurrence. "Spontaneous" pertains to a possible mechanism of origin of the disease. These are not equivalent terms. The rarity of BSE in North America qualifies it as a sporadic disease, but this low incidence does not provide information about cause. For the two reported North American BSE cases, exposure to contaminated MBM remains the most likely culprit. However, other mechanisms are still possible, including cross-infection by sheep with scrapie or cervids with CWD, horizontal transmission from cattle with endemic BSE, and spontaneous disease in individual cattle. Based on our understanding of other TSEs, the spontaneous mechanism is probably the least likely. Thus, "idiopathic" BSE--that is, BSE of unknown etiology--might be a better term to describe the origin of this malady.
snip...
References
S. B. Prusiner, Proc. Natl. Acad. Sci. U.S.A 95, 13363 (1998) [Medline]. P. G. Smith, R. Bradley, Br. Med. Bull. 66, 185 (2003) [Medline]. C. Weissmann, A. Aguzzi, Curr. Opin. Neurobiol. 7, 695 (1997) [Medline]. A. F. Hill et al., J. Gen. Virol. 80, 11 (1999) [Medline]. R. Chiesa et al., J. Virol. 77, 7611 (2003) [Medline]. G. Legname et al., Science 305, 673 (2004). D. Westaway et al., Cell 76, 117 (1994) [Medline]. B. Chesebro, Science 279, 42 (1998). A. G. Biacabe et al., EMBO Rep. 5, 110 (2004) [Medline]. Y. Yamakawa et al., Jpn. J. Infect. Dis. 56, 221 (2003) [Medline]. C. Casalone et al., Proc. Natl. Acad. Sci. U.S.A. 101, 3065 (2004) [Medline]. E. F. Houston et al., J. Gen. Virol. 83, 1247 (2002) [Medline].
Laboratory of Persistent Viral Diseases Bruce W. Chesebro, M.D., Chief The Laboratory of Persistent Viral Diseases (LPVD) is concerned with studies of persistent active or latent viral or prion disease infections. Investigators place particular emphasis on persistent infections of the nervous system and of the hemopoietic and lymphoid systems. The laboratory is also studying the roles of persistent infection in the development of retrovirus-induced immunosuppression. Models being examined include prion diseases of various species, murine and human retroviruses, and tick-borne encephalitis viruses.
http://www.sciencemag.org/cgi/content/full/305/5692/1918
Terry S. Singeltary Sr. P.O. Box 42 Bacliff, Texas USA 77518
As of January 31, 2010, there were 1,701 flocks participating in the Scrapie Flock Certification Program (SFCP). Of these flocks, 1,094 were complete monitored flocks, 551 were certified, 51 were export monitored, and 5 were selective monitored flocks (Figures 1 and la). Six flocks were enrolled or certified during January (Figure 2). SFCP open statuses by fiscal year from FY 1997 to FY 2010 are depicted in Chart 1.
Infected and Source Flocks
As of January 31, 2010, there were 11 scrapie infected and source flocks with open statuses (Figure 3). There were no flocks designated as infected or source in January. In FY 2010, two new infected flocks and two new source flocks were reported (Figure 4); eight flocks completed a clean-up plan and were released (Figure 5). The ratio of infected and source flocks released to newly identified infected and source flocks for FY 2010 = 2 : 1. New infected and source statuses from FY 1997 to FY 2010 are depicted in Chart 2.
Positive Scrapie Cases
As of January 31, 2010, 24 positive cases in sheep or goats were reported by the National Veterinary Services Laboratories (NVSL); 14 were field cases and 10 were Regulatory Scrapie Slaughter Surveillance (RSSS) cases collected between October 1,2009 and January 31,2010 and confirmed by February 19,2010 (Figure 6). Three RSSS cases and one field case were diagnosed as Nor98-like scrapie. Field cases are positive animals tested as part of a disease investigation including potentially exposed, exposed, and suspect animals. Twenty one cases of scrapie in goats have been confirmed by NVSL since implementation of the regulatory changes in FY 2002 (Figure 7). 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 has been held in quarantine for research by USDA's Agricultural Research Service since 2008.
Regulatory Scrapie Slaughter Surveillance (RSSS)
RSSS started April 1, 2003. It is a targeted slaughter surveillance program which is designed to identify infected flocks. Samples have been collected from 246,453 animals since April 1, 2003. There have been 431 NVSL confirmed positive animals since the beginning ofRSSS. As of January 31, 2010, 15,184 samples have been collected in FY 2010. Seven samples collected in FY 2010 have tested positive for classical scrapie"; the face colors of the positive sheep were 5 black-face and 2 mottled-face. Three samples (2 mottled-face and 1 white-face sheep) tested positive for Nor98-like scrapie. The percent of samples that have tested positive for each face color from FY 2003 through 2010 is depicted in Chart 3. Cumulative regional sample collection numbers are shown in Chart 4 and are based upon the state in which the animal was tagged. The number ofRSSS animals collected for FY 2010 by month and by region where collected is shown in Chart 5. A monthly comparison ofRSSS collections by fiscal year is displayed in Chart 6. A retrospective 6 month rolling average of the percent positive, black-faced sheep sampled at RSSS collections sites is shown in Chart 7.
*RSSS positives are reported based on collection date and may have been confirmed after January 31,2010.
Animals Sampled for Scrapie Testing
As of January 31, 2010,15,693 animals have been sampled for scrapie testing: 15,184 RSSS samples, 428 regulatory field cases, and 81 live-animal biopsies (Chart 8).
This report is based on information and test results available at the time of report generation. Numbers are subject to change due to later reporting of test results and updates in the database.
http://www.aphis.usda.gov/animal_health/animal_diseases/scrapie/downloads/monthly_scrapie_rpt.pps
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
Atypical Nor-98 states in this report for January 2010 include ; Maine, Pennsylvania, Ohio, and Oregon
kind regards, terry
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
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
Tuesday, April 28, 2009
Nor98-like Scrapie in the United States of America
http://nor-98.blogspot.com/2009/04/nor98-like-scrapie-in-united-states-of.html
P03.141
Aspects of the Cerebellar Neuropathology in Nor98
Gavier-Widén, D1; Benestad, SL2; Ottander, L1; Westergren, E1 1National Veterinary Insitute, Sweden; 2National Veterinary Institute,
Norway Nor98 is a prion disease of old sheep and goats. This atypical form of scrapie was first described in Norway in 1998. Several features of Nor98 were shown to be different from classical scrapie including the distribution of disease associated prion protein (PrPd) accumulation in the brain. The cerebellum is generally the most affected brain area in Nor98. The study here presented aimed at adding information on the neuropathology in the cerebellum of Nor98 naturally affected sheep of various genotypes in Sweden and Norway. A panel of histochemical and immunohistochemical (IHC) stainings such as IHC for PrPd, synaptophysin, glial fibrillary acidic protein, amyloid, and cell markers for phagocytic cells were conducted. The type of histological lesions and tissue reactions were evaluated. The types of PrPd deposition were characterized. The cerebellar cortex was regularly affected, even though there was a variation in the severity of the lesions from case to case. Neuropil vacuolation was more marked in the molecular layer, but affected also the granular cell layer. There was a loss of granule cells. Punctate deposition of PrPd was characteristic. It was morphologically and in distribution identical with that of synaptophysin, suggesting that PrPd accumulates in the synaptic structures. PrPd was also observed in the granule cell layer and in the white matter. The pathology features of Nor98 in the cerebellum of the affected sheep showed similarities with those of sporadic Creutzfeldt-Jakob disease in humans.
***The pathology features of Nor98 in the cerebellum of the affected sheep showed similarities with those of sporadic Creutzfeldt-Jakob disease in humans.
http://www.prion2007.com/pdf/Prion%20Book%20of%20Abstracts.pdf
PR-26
NOR98 SHOWS MOLECULAR FEATURES REMINISCENT OF GSS
R. Nonno1, E. Esposito1, G. Vaccari1, E. Bandino2, M. Conte1, B. Chiappini1, S. Marcon1, M. Di Bari1, S.L. Benestad3, U. Agrimi1 1 Istituto Superiore di Sanità, Department of Food Safety and Veterinary Public Health, Rome, Italy (romolo.nonno@iss.it); 2 Istituto Zooprofilattico della Sardegna, Sassari, Italy; 3 National Veterinary Institute, Department of Pathology, Oslo, Norway
Molecular variants of PrPSc are being increasingly investigated in sheep scrapie and are generally referred to as "atypical" scrapie, as opposed to "classical scrapie". Among the atypical group, Nor98 seems to be the best identified. We studied the molecular properties of Italian and Norwegian Nor98 samples by WB analysis of brain homogenates, either untreated, digested with different concentrations of proteinase K, or subjected to enzymatic deglycosylation. The identity of PrP fragments was inferred by means of antibodies spanning the full PrP sequence. We found that undigested brain homogenates contain a Nor98-specific PrP fragment migrating at 11 kDa (PrP11), truncated at both the C-terminus and the N-terminus, and not N-glycosylated. After mild PK digestion, Nor98 displayed full-length PrP (FL-PrP) and N-glycosylated C-terminal fragments (CTF), along with increased levels of PrP11. Proteinase K digestion curves (0,006-6,4 mg/ml) showed that FL-PrP and CTF are mainly digested above 0,01 mg/ml, while PrP11 is not entirely digested even at the highest concentrations, similarly to PrP27-30 associated with classical scrapie. Above 0,2 mg/ml PK, most Nor98 samples showed only PrP11 and a fragment of 17 kDa with the same properties of PrP11, that was tentatively identified as a dimer of PrP11. Detergent solubility studies showed that PrP11 is insoluble in 2% sodium laurylsorcosine and is mainly produced from detergentsoluble, full-length PrPSc. Furthermore, among Italian scrapie isolates, we found that a sample with molecular and pathological properties consistent with Nor98 showed plaque-like deposits of PrPSc in the thalamus when the brain was analysed by PrPSc immunohistochemistry. Taken together, our results show that the distinctive pathological feature of Nor98 is a PrP fragment spanning amino acids ~ 90-155. This fragment is produced by successive N-terminal and C-terminal cleavages from a full-length and largely detergent-soluble PrPSc, is produced in vivo and is extremely resistant to PK digestion.
*** Intriguingly, these conclusions suggest that some pathological features of Nor98 are reminiscent of Gerstmann-Sträussler-Scheinker disease.
119
http://www.neuroprion.com/pdf_docs/conferences/prion2006/abstract_book.pdf
A newly identified type of scrapie agent can naturally infect sheep with resistant PrP genotypes
Annick Le Dur*,?, Vincent Béringue*,?, Olivier Andréoletti?, Fabienne Reine*, Thanh Lan Laï*, Thierry Baron§, Bjørn Bratberg¶, Jean-Luc Vilotte?, Pierre Sarradin**, Sylvie L. Benestad¶, and Hubert Laude*,?? +Author Affiliations
*Virologie Immunologie Moléculaires and ?Génétique Biochimique et Cytogénétique, Institut National de la Recherche Agronomique, 78350 Jouy-en-Josas, France; ?Unité Mixte de Recherche, Institut National de la Recherche Agronomique-Ecole Nationale Vétérinaire de Toulouse, Interactions Hôte Agent Pathogène, 31066 Toulouse, France; §Agence Française de Sécurité Sanitaire des Aliments, Unité Agents Transmissibles Non Conventionnels, 69364 Lyon, France; **Pathologie Infectieuse et Immunologie, Institut National de la Recherche Agronomique, 37380 Nouzilly, France; and ¶Department of Pathology, National Veterinary Institute, 0033 Oslo, Norway
Edited by Stanley B. Prusiner, University of California, San Francisco, CA (received for review March 21, 2005)
Abstract Scrapie in small ruminants belongs to transmissible spongiform encephalopathies (TSEs), or prion diseases, a family of fatal neurodegenerative disorders that affect humans and animals and can transmit within and between species by ingestion or inoculation. Conversion of the host-encoded prion protein (PrP), normal cellular PrP (PrPc), into a misfolded form, abnormal PrP (PrPSc), plays a key role in TSE transmission and pathogenesis. The intensified surveillance of scrapie in the European Union, together with the improvement of PrPSc detection techniques, has led to the discovery of a growing number of so-called atypical scrapie cases. These include clinical Nor98 cases first identified in Norwegian sheep on the basis of unusual pathological and PrPSc molecular features and "cases" that produced discordant responses in the rapid tests currently applied to the large-scale random screening of slaughtered or fallen animals. Worryingly, a substantial proportion of such cases involved sheep with PrP genotypes known until now to confer natural resistance to conventional scrapie. Here we report that both Nor98 and discordant cases, including three sheep homozygous for the resistant PrPARR allele (A136R154R171), efficiently transmitted the disease to transgenic mice expressing ovine PrP, and that they shared unique biological and biochemical features upon propagation in mice. These observations support the view that a truly infectious TSE agent, unrecognized until recently, infects sheep and goat flocks and may have important implications in terms of scrapie control and public health.
http://www.pnas.org/content/102/44/16031.abstract
Monday, December 1, 2008 When Atypical Scrapie cross species barriers
Authors
Andreoletti O., Herva M. H., Cassard H., Espinosa J. C., Lacroux C., Simon S., Padilla D., Benestad S. L., Lantier F., Schelcher F., Grassi J., Torres, J. M., UMR INRA ENVT 1225, Ecole Nationale Veterinaire de Toulouse.France; ICISA-INlA, Madrid, Spain; CEA, IBiTec-5, DSV, CEA/Saclay, Gif sur Yvette cedex, France; National Veterinary Institute, Postboks 750 Sentrum, 0106 Oslo, Norway, INRA IASP, Centre INRA de Tours, 3738O Nouzilly, France.
Content
Atypical scrapie is a TSE occurring in small ruminants and harbouring peculiar clinical, epidemiological and biochemical properties. Currently this form of disease is identified in a large number of countries. In this study we report the transmission of an atypical scrapie isolate through different species barriers as modeled by transgenic mice (Tg) expressing different species PRP sequence.
The donor isolate was collected in 1995 in a French commercial sheep flock. inoculation into AHQ/AHQ sheep induced a disease which had all neuro-pathological and biochemical characteristics of atypical scrapie. Transmitted into Transgenic mice expressing either ovine or PrPc, the isolate retained all the described characteristics of atypical scrapie.
Surprisingly the TSE agent characteristics were dramatically different v/hen passaged into Tg bovine mice. The recovered TSE agent had biological and biochemical characteristics similar to those of atypical BSE L in the same mouse model. Moreover, whereas no other TSE agent than BSE were shown to transmit into Tg porcine mice, atypical scrapie was able to develop into this model, albeit with low attack rate on first passage.
Furthermore, after adaptation in the porcine mouse model this prion showed similar biological and biochemical characteristics than BSE adapted to this porcine mouse model. Altogether these data indicate.
(i) the unsuspected potential abilities of atypical scrapie to cross species barriers
(ii) the possible capacity of this agent to acquire new characteristics when crossing species barrier
These findings raise some interrogation on the concept of TSE strain and on the origin of the diversity of the TSE agents and could have consequences on field TSE control measures.
http://www.neuroprion.org/resources/pdf_docs/conferences/prion2008/abstract-book-prion2008.pdf
NOR-98 ATYPICAL SCRAPIE 5 cases documented in USA in 5 different states USA 2007
http://nor-98.blogspot.com/2008/04/seac-spongiform-encephalopathy-advisory.html
Tuesday, June 3, 2008
SCRAPIE USA UPDATE JUNE 2008 NOR-98 REPORTED PA
http://nor-98.blogspot.com/2008/06/scrapie-usa-update-june-2008-nor-98.html
http://nor-98.blogspot.com/
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
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
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://www.bseinquiry.gov.uk/files/yb/1994/02/07002001.pdf
NEW URL BELOW ;
http://web.archive.org/web/20030517224223/http://www.bseinquiry.gov.uk/files/yb/1994/02/07002001.pdf
Rangen Inc 2/11/10
Department of Health and Human Services Public Health Service Food and Drug Administration Seattle District Pacific Region 22201 23rd Drive SE Bothell, WA 98021-4421 Telephone: 425-486-8788 FAX: 425-483-4996
February 11, 2010
CERTIFIED MAIL
RETURN RECEIPT REQUESTED
In reply refer to Warning Letter SEA 10-11
Christopher T. Rangen, President Rangen, Inc. 115-13th Avenue South PO Box 706 Buhl, Idaho 83316
WARNING LETTER
Dear Mr. Rangen: On June 9-11, 2009, U.S. Food and Drug Administration (FDA) investigators inspected your animal feed manufacturing facilities located at 115-13th Avenue South, Buhl, Idaho. The inspection revealed significant deviations from the requirements set forth in Title 21, Code of Federal Regulations, Section 589.2000 (21 C.F.R. 589.2000), Animal Proteins Prohibited in Ruminant Feed. This regulation is intended to prevent the establishment and amplification of Bovine Spongiform Encephalopathy (BSE). You failed to follow the requirements of this regulation, resulting in products being manufactured and distributed by your facility that were adulterated within the meaning of section 402(a)(4) of the Federal Food, Drug, and Cosmetic Act (the Act), 21 U.S.C. § 342(a)(4), and misbranded within the meaning of section 403(a)(1) of the Act, 21 U.S.C. § 343(a)(1). Our investigation determined that adulteration resulted from the failure of your firm to provide for measures to avoid commingling or cross-contamination. The adulterated feed was subsequently misbranded because it was not properly labeled. Specifically, we found:
1. Your firm failed to provide for and use cleanout procedures or other means adequate to prevent carry-over of products that contain or may contain proteins derived from mammalian tissues into animal feed that may be used for ruminants, as required by 21 CFR 589.2000(e)(1)(iii)(B). Since your feed is prepared, packed, or held under these conditions it is, therefore, adulterated under section 402(a)(4) of the Act, 21 U.S.C. § 342(a)(4).
. Mink feed that was not labeled "Do not feed to cattle or other ruminants," in accordance with 21 CFR 589.2000(e)(1)(i) and that, therefore, might be fed to ruminants, was produced using the same equipment as aquaculture feed that contains proteins derived from mammalian tissues, such as meat and bone meal. You conducted no clean-outs or flushes of equipment to remove proteins derived from mammalian tissues that may have been present before manufacturing the mink feed that might be fed to ruminants.
. The auger trucks you used to deliver bulk mink feed which contained or may have contained proteins derived from mammalian tissues were not subject to an effective clean-out prior to their use to deliver bulk animal feed, including ruminant feed, that did not contain such materials. There were no procedures to clean the trucks to remove proteins derived from mammalian tissues before shipment of animal feeds that did not contain such materials.
2. You failed to label all products which contained or may have contained proteins derived from mammalian tissues with the statement, "Do not feed to cattle or other ruminants," as required by 21 C.F.R. 589.2000(e)(1)(i). Such products are misbranded under Section 403(a)(1) of the Act, 21 U.S.C. § 343(a)(1). The misbranded product includes bulk mink feed.
. On June 9, 2009, the investigators observed approximately (b)(4) pallets of (b)(4) 50 pound bags of (b)(4) MINK FEED, lot 06/05/09. All bagged mink feed, as well as approximately (b)(4)% of bulk mink feed, manufactured at your facility, was produced using the aquaculture feed production equipment used to produce feed containing proteins derived from mammalian tissues. Because mink feed produced using this equipment may have contained mammalian tissues, it was not properly labeled, as required by 21 C.F.R. 589.2000(e)(1)(i).
This letter is not intended to serve as an all-inclusive list of violations at your facility. As a manufacturer of materials intended for animal feed use, you are responsible for ensuring your overall operation and the products you manufacture and distribute are in compliance with the law. You should take prompt action to correct the above violations and you should establish a system whereby violations do not occur. Failure to promptly correct these violations may result in regulatory action, such seizure and/or injunction, without further notice.
We acknowledge your July 31, 2009 letter detailing procedures you had implemented or planned to implement to prevent future violations of FDA regulations relating to mammalian proteins in animal feed. In particular the letter stated that Rangen would no longer purchase meat and bone meal for use in any of its animal feeds and that existing inventories of mammalian protein ingredients would be exhausted by December 31, 2009. Division Manager, Joy Kinyon made similar assertions in the course of FDA's June 2009 inspection. The July 31, 2009 letter further set out procedures Rangen would use to remedy observed violations of FDA regulations while mammalian proteins were still being used at Rangen. Finally you explained steps taken to recover or relabel feed that may have been contaminated due to commingling resulting from your manufacturing and distribution procedures. Within fifteen (15) working days of receiving this letter you should, in writing, confirm the steps you took prior to receiving this letter and notify FDA of steps you have taken since receiving this letter to bring your firm into compliance with the law. Your response should include each step that has been taken or will be taken to correct the violations and prevent their recurrence. If corrective action cannot be completed within fifteen (15) working days, state the reason for the delay and the time frame within which the corrections will be completed. Please include copies of any available documentation demonstrating that corrections have been made.
Your written reply should be directed to Scott A. Nabe, Compliance Officer, U.S. Food and Drug Administration, 22201 23rd Drive SE, Bothell, Washington 98021-4421. If you have any questions about this letter, please contact Mr. Nabe at (425) 483-4753.
Sincerely,
/s/
Charles M. Breen District Director Seattle District
cc: Joy A. Kinyon, Division Manager, Aquaculture Feeds-General Feeds Rangen, Inc. PO Box 706 115-13th Avenue South Buhl, Idaho 83316
http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/ucm201893.htm
Monday, March 1, 2010
ANIMAL PROTEIN I.E. MAD COW FEED IN COMMERCE A REVIEW 2010
http://madcowfeed.blogspot.com/2010/03/animal-protien-ie-mad-cow-feed-in.html
Tuesday, March 2, 2010
Animal Proteins Prohibited in Ruminant Feed/Adulterated/Misbranded Rangen Inc 2/11/10 USA
http://madcowfeed.blogspot.com/2010/03/animal-proteins-prohibited-in-ruminant.html
. Mink feed that was not labeled "Do not feed to cattle or other ruminants," in accordance with 21 CFR 589.2000(e)(1)(i) and that, therefore, might be fed to ruminants, was produced using the same equipment as aquaculture feed that contains proteins derived from mammalian tissues, such as meat and bone meal. You conducted no clean-outs or flushes of equipment to remove proteins derived from mammalian tissues that may have been present before manufacturing the mink feed that might be fed to ruminants.
<<< href="http://www.cdc.gov/eid/content/13/12/1887.htm?s_cid=eid1887_e">http://www.cdc.gov/eid/content/13/12/1887.htm?s_cid=eid1887_e
Over the next 8-10 weeks, approximately 40% of all the adult mink on the farm died from TME.
snip...
The rancher was a ''dead stock'' feeder using mostly (>95%) downer or dead dairy cattle...
http://web.archive.org/web/20030516051623/http://www.bseinquiry.gov.uk/files/mb/m09/tab05.pdf
An update on atypical BSE and other TSE in North America. Please remember, the typical U.K. c-BSE, the atypical l-BSE (BASE), and h-BSE have all been documented in North America, along with the typical scrapie's, and atypical Nor-98 Scrapie, and to date, 2 different strains of CWD, and also TME. All these TSE in different species have been rendered and fed to food producing animals for humans and animals in North America (TSE in cats and dogs ?), and that the trading of these TSEs via animals and products via the USA and Canada has been immense over the years, decades.
SEE PAGE 114 ;
http://ww2.isid.org/Downloads/14th_ICID_ISE_Abstracts.pdf
http://transmissiblespongiformencephalopathy.blogspot.com/
LIKE i said before, the OIE not only sold their soul to the devil over the BSE MRR, they sold yours too ;
Wednesday, February 10, 2010
NAIS MAD COW TRACEABILITY DUMPED BY USDA APHIS 2010
http://naiscoolyes.blogspot.com/2010/02/nais-mad-cow-traceability-dumped-by.html
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
Scientific Report of the European Food Safety Authority on the Assessment of the Geographical BSE Risk (GBR) of the USA Question number: EFSA-Q-2003-083
Adopted: 1 July 2004 Summary (0.1Mb)
Report (0.2Mb)
Summary
The European Food Safety Authority and its Scientific Expert Working Group on the Assessment of the Geographical Bovine Spongiform Encephalopathy (BSE) Risk (GBR) were asked by the European Commission (EC) to provide an up-to-date scientific report on the GBR in the United States of America, i.e. the likelihood of the presence of one or more cattle being infected with BSE, pre-clinically as well as clinically, in USA. This scientific report addresses the GBR of USA as assessed in 2004 based on data covering the period 1980-2003.
The BSE agent was probably imported into USA and could have reached domestic cattle in the middle of the eighties. These cattle imported in the mid eighties could have been rendered in the late eighties and therefore led to an internal challenge in the early nineties. It is possible that imported meat and bone meal (MBM) into the USA reached domestic cattle and leads to an internal challenge in the early nineties.
A processing risk developed in the late 80s/early 90s when cattle imports from BSE risk countries were slaughtered or died and were processed (partly) into feed, together with some imports of MBM. This risk continued to exist, and grew significantly in the mid 90’s when domestic cattle, infected by imported MBM, reached processing. Given the low stability of the system, the risk increased over the years with continued imports of cattle and MBM from BSE risk countries.
EFSA concludes that the current GBR level of USA is III, i.e. it is likely but not confirmed that domestic cattle are (clinically or pre-clinically) infected with the BSE-agent. As long as there are no significant changes in rendering or feeding, the stability remains extremely/very unstable. Thus, the probability of cattle to be (pre-clinically or clinically) infected with the BSE-agent persistently increases.
http://www.efsa.europa.eu/EFSA/efsa_locale-1178620753812_1211902594180.htm
Monday, November 23, 2009
BSE GBR RISK ASSESSMENTS UPDATE NOVEMBER 23, 2009 COMMISSION OF THE EUROPEAN COMMUNITIES AND O.I.E.
http://docket-aphis-2006-0041.blogspot.com/2009/11/bse-gbr-risk-assessments-update.html
Greetings,
HAVE we come to a point to where sub-clinical disease is an acceptable factor ???
LEGALLY, is it o.k. to be sub-clinically infected from a contaminated product ???
IF SO, what is the legality from the second passage infection from that sub-clinical host to clinical infection via the pass it forward and or friendly fire mode of transmission for any iatrogenic Transmissible Spongiform encephalopathy to second, third, fourth passage ???
CJD USA RISING, with UNKNOWN PHENOTYPE ;
5 Includes 41 cases in which the diagnosis is pending, and 17 inconclusive cases; 6 Includes 46 cases with type determination pending in which the diagnosis of vCJD has been excluded.
http://www.cjdsurveillance.com/pdf/case-table.pdf
WHY DO FARMERS AND THEIR WIVES WITH BSE HERDS, ONLY HAVE SPORADIC CJD ???
Monday, May 19, 2008
SPORADIC CJD IN FARMERS, FARMERS WIVES, FROM FARMS WITH BSE HERD AND ABATTOIRS
http://bseinquiry.blogspot.com/
Sunday, August 10, 2008
A New Prionopathy OR more of the same old BSe and sporadic CJD
http://creutzfeldt-jakob-disease.blogspot.com/2008/08/new-prionopathy-or-more-of-same-old-bse.html
full text ;
Saturday, February 27, 2010
SEAC Agenda 104th meeting on Friday 5th March 2010
http://seac992007.blogspot.com/2010/02/seac-agenda-104th-meeting-on-friday-5th.html
Saturday, February 27, 2010
FINAL REPORT OF THE TESTING OF THE BELGIAN (VERMONT) SHEEP February 27, 2010
http://foiamadsheepmadrivervalley.blogspot.com/2010/02/final-report-of-testing-of-belgian.html
Prions: Protein Aggregation and Infectious Diseases
ADRIANO AGUZZI AND ANNA MARIA CALELLA
Institute of Neuropathology, University Hospital of Zurich, Zurich, Switzerland
snip...
3. Sporadic Creutzfeldt-Jakob disease Approximately 85% of all human prion diseases are sporadic forms of CJD. For sCJD, there is no association with a mutant PRNP allele, nor is there any epidemiological evidence for exposure to a TSE agent through contact with people or animals infected with TSEs. sCJD cases are currently subclassified according to the methionine/valine polymorphism at codon 129 of the PRNP gene and the size and glycoform ratio of proteaseresistant prion protein identified on western blot (type 1 or type 2) (174). Heterozygosity (Met/Val) at PrP codon 129 appears to be associated with a lower risk (378) and/or prolonged incubation time (119, 387). The lack of routine laboratory testing for preclinical diagnosis makes the search for agent sources and other risk factors extremely difficult. At present, the means of acquisition of a TSE agent in these patients remains a mystery. So far, there is no evidence for spontaneous PrPSc formation in any animal or human TSE. In humans, the peak age incidence of sporadic CJD is 55–60 years. However, if spontaneous misfolding were the primary event, one might expect a continuously increasing incidence with age because more time would allow more opportunity for rare misfolding events.
snip...
Physiol Rev • VOL 89 • OCTOBER 2009 • www.prv.org
http://physrev.physiology.org/cgi/content/abstract/89/4/1105
Science 24 September 2004: Vol. 305. no. 5692, pp. 1918 - 1921 DOI: 10.1126/science.1103581
Perspectives BIOMEDICINE:
A Fresh Look at BSE
Bruce Chesebro*
snip...
BSE caused by spontaneous misfolding of the prion protein has not been proven.
snip...
What can we conclude so far about BSE in North America? Is the BSE detected in two North American cows sporadic or spontaneous or both? "Sporadic" pertains to the rarity of disease occurrence. "Spontaneous" pertains to a possible mechanism of origin of the disease. These are not equivalent terms. The rarity of BSE in North America qualifies it as a sporadic disease, but this low incidence does not provide information about cause. For the two reported North American BSE cases, exposure to contaminated MBM remains the most likely culprit. However, other mechanisms are still possible, including cross-infection by sheep with scrapie or cervids with CWD, horizontal transmission from cattle with endemic BSE, and spontaneous disease in individual cattle. Based on our understanding of other TSEs, the spontaneous mechanism is probably the least likely. Thus, "idiopathic" BSE--that is, BSE of unknown etiology--might be a better term to describe the origin of this malady.
snip...
References
S. B. Prusiner, Proc. Natl. Acad. Sci. U.S.A 95, 13363 (1998) [Medline]. P. G. Smith, R. Bradley, Br. Med. Bull. 66, 185 (2003) [Medline]. C. Weissmann, A. Aguzzi, Curr. Opin. Neurobiol. 7, 695 (1997) [Medline]. A. F. Hill et al., J. Gen. Virol. 80, 11 (1999) [Medline]. R. Chiesa et al., J. Virol. 77, 7611 (2003) [Medline]. G. Legname et al., Science 305, 673 (2004). D. Westaway et al., Cell 76, 117 (1994) [Medline]. B. Chesebro, Science 279, 42 (1998). A. G. Biacabe et al., EMBO Rep. 5, 110 (2004) [Medline]. Y. Yamakawa et al., Jpn. J. Infect. Dis. 56, 221 (2003) [Medline]. C. Casalone et al., Proc. Natl. Acad. Sci. U.S.A. 101, 3065 (2004) [Medline]. E. F. Houston et al., J. Gen. Virol. 83, 1247 (2002) [Medline].
Laboratory of Persistent Viral Diseases Bruce W. Chesebro, M.D., Chief The Laboratory of Persistent Viral Diseases (LPVD) is concerned with studies of persistent active or latent viral or prion disease infections. Investigators place particular emphasis on persistent infections of the nervous system and of the hemopoietic and lymphoid systems. The laboratory is also studying the roles of persistent infection in the development of retrovirus-induced immunosuppression. Models being examined include prion diseases of various species, murine and human retroviruses, and tick-borne encephalitis viruses.
http://www.sciencemag.org/cgi/content/full/305/5692/1918
Terry S. Singeltary Sr. P.O. Box 42 Bacliff, Texas USA 77518
Monday, December 14, 2009
Similarities between Forms of Sheep Scrapie and Creutzfeldt-Jakob Disease Are Encoded by Distinct Prion Types
(American Journal of Pathology. 2009;175:2566-2573.) © 2009 American Society for Investigative Pathology DOI: 10.2353/ajpath.2009.090623
Similarities between Forms of Sheep Scrapie and Creutzfeldt-Jakob Disease Are Encoded by Distinct Prion Types
Wiebke M. Wemheuer*, Sylvie L. Benestad, Arne Wrede*, Ulf Schulze-Sturm*, Wilhelm E. Wemheuer, Uwe Hahmann*, Joanna Gawinecka, Ekkehard Schütz, Inga Zerr, Bertram Brenig, Bjørn Bratberg, Olivier Andréoletti¶ and Walter J. Schulz-Schaeffer* From the Prion and Dementia Research Unit,* Department of Neuropathology, and the National Transmissible Spongiform Encephalopathies Reference Center, Department of Neurology, University Medical Center Goettingen, Goettingen, Germany; the Department of Pathology, National Veterinary Institute, Oslo, Norway; the Institute of Veterinary Medicine, Faculty for Agricultural Sciences, University of Goettingen, Goettingen, Germany; and Animal Health,¶ Interactions Hôte Agent Pathogène, Ecole Nationale Vétérinaire de Toulouse, Toulouse, France
Transmissible spongiform encephalopathies such as scrapie in sheep, Creutzfeldt-Jakob disease (CJD) in humans, and bovine sporadic encephalopathy in cattle are characterized by the accumulation of a misfolded protein: the pathological prion protein. Ever since bovine sporadic encephalopathy was discovered as the likely cause of the new variant of CJD in humans, parallels between human and animal transmissible spongiform encephalopathies must be viewed under the aspect of a disease risk for humans. In our study we have compared prion characteristics of different forms of sheep scrapie with those of different phenotypes of sporadic CJD. The disease characteristics of sporadic CJD depend considerably on the prion type 1 or 2. Our results show that there are obvious parallels between sporadic CJD type 1 and the so-called atypical/Nor98 scrapie. These parelleles apply to the deposition form of pathological prion protein in the brain, detected by the paraffin-embedded-tissue blot and the prion aggregate stability with regard to denaturation by the chaotropic salt guanidine hydrochloride. The same applies to sporadic CJD type 2 and classical scrapie. The observed parallels between types of sporadic CJD and types of sheep scrapie demonstrate that distinct groups of prion disease exist in different species. This should be taken into consideration when discussing interspecies transmission.
snip...
Different Scrapie Prion Types Show Similarities to Human Prion Types: PrPsc Deposition Pattern and Western Blot Results
After proteinase K-digestion and Western blot analysis, two different prion protein types were detectable in clinically distinct human Creutzfeldt-Jakob diseases.30 Depending on the PrPSc types 1 or 2 (Figure 1C) a difference in the form of PrPSc aggregates and the neuroanatomical distribution in the brain could be observed similar to differences identified in sheep scrapie. In patients with CJD that accumulate PrPSc type 1, reticular/synaptic were detected in cortical structures (Figure 3F), subcortical nuclei, and the cerebellar cortex (Figure 4D). By contrast, prion aggregates in patients accumulating PrPSc type 2 appeared to be complex as they displayed in particular perivacuolar, intra- and perineuronal, and/or plaque-like forms (Figures 3C and 5B). These differences concerning the deposition form of PrPSc aggregates were independent of the methionine/valine polymorphism at codon 129 of the PRNP. The topographical pattern of PrPSc distribution between these two prion types differed as follows: type 1 deposits were typically restricted to gray matter structures, while all type 2 patients showed deposits in the white matter. In patients with type 1 PrPSc the midbrain and brain stem structures were relatively spared, but in patients with type 2 PrPSc brain stem and midbrain were heavily affected. Although these prion type-related topographical differences are not completely identical to those in sheep scrapie, a comparable connection between prion type and deposition pattern is evident.
Aggregate Stability Regarding Denaturation
Similar to scrapie in sheep, the stability of PrPSc aggregates of human sporadic CJD against denaturation with GdnHCl showed two groups: denaturation-resistant and denaturation-sensitive PrPSc aggregates. This property correlated with the prion protein type according to Parchi et al8 and is independent from the physiologically occurring methionine/valine polymorphism at codon 129 of the PRNP. By membrane adsorption after GdnHCl denaturation and proteinase K-digestion, human PrPSc type 1 proved to be less stable than human PrPSc type 2. While human PrPSc type 2 was detectable up to GdnHCl concentrations between 3M and 4M, human PrPSc type 1 was stable up to 2M GdnHCl. Neither methionine nor valine at codon 129 in type 1 or type 2 seemed to alter the stability of the prion protein aggregates (Figure 5).
Summarizing the results, striking parallels between human PrPSc type 1 and atypical/Nor98 scrapie as well as human PrPSc type 2 and classical scrapie are observed with regard to PrPSc deposition and stability of the prion aggregates.
Discussion
In humans, different prion types are linked with clinically and neuropathologically distinct prion diseases.8 The present work emphasizes that the differences in deposition characteristics and stability with regard to denaturation between atypical/Nor98 and classical scrapie also account for different prion types. Moreover, the two scrapie types that have been characterized show a number of striking similarities with human PrPSc types in sporadic CJD. Hence, we propose that the existence of different PrPSc types might be a common denominator of prion diseases in humans and animals. Since these two prion types show an across-the-species comparability with similar biochemical and pathological characteristics, it is most likely that they exist due to a different conformational pattern of the disease-related prion protein.
Prion Types Depend on Conformation
The interpretation that the conformation of PrPSc accounts for prion types is supported by different proteinase K-cleavage sites of human prion types9 and the propagation of mutation-associated prion characteristics in human transgenic mice without PRNP-point mutation. 31 However, differences in protein stability as they have been found in this study, provide direct evidence for a conformational distinction between these molecules.32 Further support for the relation between type and conformation is also given by experiments focusing on the size of prion protein aggregates. Using virus removal filters, Kobayashi et al33 were able to show differences in the size of CJD type 1 and type 2 aggregates: PrPSc type 2 forms larger aggregates than PrPSc type 1, independent of whether the disease was sporadic, iatrogenic or acquired. This difference is clearly reflected by the morphology of the PrPSc depositions we have found in sheep scrapie and human CJD. Sporadic CJD type 1 and atypical/ Nor98 scrapie are characterized by fine (reticular) deposits, whereas CJD type 2 and classical scrapie display a complex aggregate pattern, regardless of the respective genotypes at the polymorphic positions of the PRNP that were investigated.
Prion Type Characteristics Versus Prion Strain Characteristics
Structural differences of the disease-associated protein have also been proposed as an explanation for the existence of strains. Partial digestion of the disease-associated protein with proteinase K as well as differences in antibody binding after the protein was partially denatured were used to identify structural characteristics in correlation with strain properties and different clinical TSE forms.23,34,35 It needs to be considered that the kinetics of proteinase K-digestion of PrPSc are markedly influenced by detergent effects in the buffer, demonstrating that the accessibility of the cleavage sites are variable.35 In contrast, differences in the stability against total unfolding of PrPSc seem to be a usable criterion to identify conformational differences or conformational motives. Whereas detergents affect the tertiary structure of a protein by interacting with hydrophilic and hydrophobic areas of protein molecules, chaotropic salts like GdnHCl destroy the hydrogen bonds in -helices and -sheets leading to an irregular coiled polypeptide chain.36 This is in line with the observation that detergents remove prion infectivity only partially, whereas chemicals that destroy secondary structures like chaotropic salts are highly effective. 37 However, detectable differences regarding the stability against denaturation with GdnHCl shown for various prion strains in hamsters seem to be very small compared with the ones that can be shown here for the prion types of human and ovine prion diseases. Strains could thus correspond to structural differences that are less marked than those defining types and are probably constant only under defined conditions. Influences of polymorphisms or interactions with other genetic factors like the promotor region, species-specific factors like the recently detected incorporation of polyanionic molecules into prions,38 glycosaminoglycans or other yet unknown factors of the original host may also lead to different strains in a new host within the prion types of the original species.5,39 The existence of prion types does not exclude the existence of strains. The same variations that account for strains might be the reason for differences in the clinical disease course of the natural host.
Two Different Prion Types also in BSE?
Parallel to human sporadic CJD and our results in sheep scrapie, there is increasing evidence that two prion types also exist in cattle BSE. Two presumably sporadic forms of BSE known as H-type BSE14 and bovine amyloidotic spongiform encephalopathy, also called L-type BSE,15 have been described in cattle in addition to typical/classical BSE.40 The small variation in the apparent molecular weight of the unglycosylated band of bovine amyloidotic spongiform encephalopathy is considered to be well within the range of classical BSE,41,42 which would leave H-type BSE with a considerably larger unglycosylated fragment in Western blot analysis than the second BSE type. Interestingly, bovine amyloidotic spongiform encephalopathy converts into classical BSE after serial passages in bovine-transgenic mice,43 although displaying clinically different diseases in cattle.44 From the latter experiment the authors concluded that different strains were responsible for different phenotypes. Obviously the different clinical diseases were generated by agents that belong to a single prion type. These results together with our observations emphasize the need to differentiate strictly between prion types and prion strains and demonstrate that even in cattle BSE, one prion type may contain different prion strains.
Prion Type Displays Parallels in the Pathophysiology of Disease between Species
Biochemical and morphological similarities have been used to draw parallels between forms of BSE and human prion diseases.15 Parallels between species can also be observed with regard to the route of prion infection: in classical BSE, variant CJD, and classical scrapie, all of which presumably belong to one class of prion type (type 2 in humans) according to the observations made above, the oral route of infection has been identified. These TSEs use the dorsal motor nucleus of the vagus nerve as an entry site into the brain.29,45,46 This observation suggests that distinct prion types in human and animal TSEs possibly have an impact on the pathogenesis of prion diseases.
Conclusion
As the prion protein is a highly conserved protein in terms of evolution, parallels between characteristics of prion types in TSEs of different species are of interest. In the present study, we report previously unknown similarities between sheep scrapie forms and human sporadic CJD types. We propose that the observed similarities between sheep scrapie and sporadic CJD in humans justify new interspecies groups of prion diseases in which prion types, not prion strains, are the major determinant for prion disease forms. While epidemiology implies that classical scrapie is not related to human TSEs,47 the atypical/Nor98 scrapie risk for human transmission has not yet been elucidated. Currently there is no compelling evidence that sCJD has a different origin than sporadic genesis. However, the finding of prion types with an across-the-species comparability might provide further understanding of the pathogenesis in prion diseases.
Acknowledgments We thank Tatjana Pfander, Nadine Rupprecht, and Kerstin Brekerbohm for their skillful technical assistance.
http://ajp.amjpathol.org/cgi/content/abstract/175/6/2566
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
P.5.21
Parallels between different forms of sheep scrapie and types of Creutzfeldt-Jakob disease (CJD)
Wiebke M. Wemheuer1, Sylvie L. Benestad2, Arne Wrede1, Wilhelm E. Wemheuer3, Tatjana Pfander1, Bjørn Bratberg2, Bertram Brenig3,Walter J. Schulz-Schaeffer1 1University Medical Center Goettingen, Germany; 2Institute of Veterinary Medicine Oslo, Norway; 3Institute of Veterinary Medicine Goettingen, Germany
Background: Scrapie in sheep and goats is often regarded as the archetype of prion diseases. In 1998, a new form of scrapie – atypical/Nor98 scrapie – was described that differed from classical scrapie in terms of epidemiology, Western blot profile, the distribution of pathological prion protein (PrPSc) in the body and its stability against proteinase K. In a similar way, distinct disease types exist in sporadic Creutzfeldt-Jakob disease (CJD). They differ with regard to their clinical outcome, Western blot profile and PrPSc deposition pattern in the central nervous system (CNS).
Objectives: The comparison of PrPSc deposits in sheep scrapie and human sporadic CJD.
Methods: Tissues of the CNS of sheep with classical scrapie, sheep with atypical/Nor98 scrapie and 20 patients with sporadic CJD were examined using the sensitive Paraffin Embedded Tissue (PET) blot method. The results were compared with those obtained by immunohistochemistry. With the objective of gaining information on the protein conformation, the PrPSc of classical and atypical/Nor98 sheep scrapie and sporadic CJD was tested for its stability against denaturation with guanidine hydrochloride (GdnHCl) using a Membrane Adsorption Assay.
Results: The PrPSc of atypical/Nor98 scrapie cases and of CJD prion type 1 patients exhibits a mainly reticular/synaptic deposition pattern in the brain and is relatively sensitive to denaturation with GdnHCl. In contrast classical scrapie cases and CJD prion type 2 patients have a more complex PrPSc deposition pattern in common that consists of larger PrPSc aggregates and the PrPSc itself is comparatively stable against denaturation.
Discussion: The similarity between CJD types and scrapie types indicates that at least two comparable forms of the misfolded prion protein exist beyond species barriers and can elicit prion diseases. It seems therefore reasonable to classify classical and atypical/Nor98 scrapie – in analogy to the existing CJD types – as different scrapie types.
http://www.prion2009.com/sites/default/files/Prion2009_Book_of_Abstracts.pdf
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 1, 2008
When Atypical Scrapie cross species barriers
http://nor-98.blogspot.com/2008/12/when-atypical-scrapie-cross-species.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
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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
Tuesday, April 28, 2009
Nor98-like Scrapie in the United States of America
http://nor-98.blogspot.com/2009/04/nor98-like-scrapie-in-united-states-of.html
Scrapie USA
http://scrapie-usa.blogspot.com/
Like lambs to the slaughter
31 March 2001
by Debora MacKenzie Magazine issue 2284
FOUR years ago, Terry Singeltary watched his mother die horribly from a degenerative brain disease. Doctors told him it was Alzheimer's, but Singeltary was suspicious. The diagnosis didn't fit her violent symptoms, and he demanded an autopsy. It showed she had died of sporadic Creutzfeldt-Jakob disease.
Most doctors believe that sCJD is caused by a prion protein deforming by chance into a killer. But Singeltary thinks otherwise. He is one of a number of campaigners who say that some sCJD, like the variant CJD related to BSE, is caused by eating meat from infected animals. Their suspicions have focused on sheep carrying scrapie, a BSE-like disease that is widespread in flocks across Europe and North America.
Now scientists in France have stumbled across new evidence that adds weight to the campaigners' fears. To their complete surprise, the researchers found that one strain of scrapie causes the same brain damage in ...
http://www.newscientist.com/article/mg16922840.300-like-lambs-to-the-slaughter.html
R.I.P. MOM hvCJD confirmed DECEMBER 14, 1997
TSS
Similarities between Forms of Sheep Scrapie and Creutzfeldt-Jakob Disease Are Encoded by Distinct Prion Types
Wiebke M. Wemheuer*, Sylvie L. Benestad, Arne Wrede*, Ulf Schulze-Sturm*, Wilhelm E. Wemheuer, Uwe Hahmann*, Joanna Gawinecka, Ekkehard Schütz, Inga Zerr, Bertram Brenig, Bjørn Bratberg, Olivier Andréoletti¶ and Walter J. Schulz-Schaeffer* From the Prion and Dementia Research Unit,* Department of Neuropathology, and the National Transmissible Spongiform Encephalopathies Reference Center, Department of Neurology, University Medical Center Goettingen, Goettingen, Germany; the Department of Pathology, National Veterinary Institute, Oslo, Norway; the Institute of Veterinary Medicine, Faculty for Agricultural Sciences, University of Goettingen, Goettingen, Germany; and Animal Health,¶ Interactions Hôte Agent Pathogène, Ecole Nationale Vétérinaire de Toulouse, Toulouse, France
Transmissible spongiform encephalopathies such as scrapie in sheep, Creutzfeldt-Jakob disease (CJD) in humans, and bovine sporadic encephalopathy in cattle are characterized by the accumulation of a misfolded protein: the pathological prion protein. Ever since bovine sporadic encephalopathy was discovered as the likely cause of the new variant of CJD in humans, parallels between human and animal transmissible spongiform encephalopathies must be viewed under the aspect of a disease risk for humans. In our study we have compared prion characteristics of different forms of sheep scrapie with those of different phenotypes of sporadic CJD. The disease characteristics of sporadic CJD depend considerably on the prion type 1 or 2. Our results show that there are obvious parallels between sporadic CJD type 1 and the so-called atypical/Nor98 scrapie. These parelleles apply to the deposition form of pathological prion protein in the brain, detected by the paraffin-embedded-tissue blot and the prion aggregate stability with regard to denaturation by the chaotropic salt guanidine hydrochloride. The same applies to sporadic CJD type 2 and classical scrapie. The observed parallels between types of sporadic CJD and types of sheep scrapie demonstrate that distinct groups of prion disease exist in different species. This should be taken into consideration when discussing interspecies transmission.
snip...
Different Scrapie Prion Types Show Similarities to Human Prion Types: PrPsc Deposition Pattern and Western Blot Results
After proteinase K-digestion and Western blot analysis, two different prion protein types were detectable in clinically distinct human Creutzfeldt-Jakob diseases.30 Depending on the PrPSc types 1 or 2 (Figure 1C) a difference in the form of PrPSc aggregates and the neuroanatomical distribution in the brain could be observed similar to differences identified in sheep scrapie. In patients with CJD that accumulate PrPSc type 1, reticular/synaptic were detected in cortical structures (Figure 3F), subcortical nuclei, and the cerebellar cortex (Figure 4D). By contrast, prion aggregates in patients accumulating PrPSc type 2 appeared to be complex as they displayed in particular perivacuolar, intra- and perineuronal, and/or plaque-like forms (Figures 3C and 5B). These differences concerning the deposition form of PrPSc aggregates were independent of the methionine/valine polymorphism at codon 129 of the PRNP. The topographical pattern of PrPSc distribution between these two prion types differed as follows: type 1 deposits were typically restricted to gray matter structures, while all type 2 patients showed deposits in the white matter. In patients with type 1 PrPSc the midbrain and brain stem structures were relatively spared, but in patients with type 2 PrPSc brain stem and midbrain were heavily affected. Although these prion type-related topographical differences are not completely identical to those in sheep scrapie, a comparable connection between prion type and deposition pattern is evident.
Aggregate Stability Regarding Denaturation
Similar to scrapie in sheep, the stability of PrPSc aggregates of human sporadic CJD against denaturation with GdnHCl showed two groups: denaturation-resistant and denaturation-sensitive PrPSc aggregates. This property correlated with the prion protein type according to Parchi et al8 and is independent from the physiologically occurring methionine/valine polymorphism at codon 129 of the PRNP. By membrane adsorption after GdnHCl denaturation and proteinase K-digestion, human PrPSc type 1 proved to be less stable than human PrPSc type 2. While human PrPSc type 2 was detectable up to GdnHCl concentrations between 3M and 4M, human PrPSc type 1 was stable up to 2M GdnHCl. Neither methionine nor valine at codon 129 in type 1 or type 2 seemed to alter the stability of the prion protein aggregates (Figure 5).
Summarizing the results, striking parallels between human PrPSc type 1 and atypical/Nor98 scrapie as well as human PrPSc type 2 and classical scrapie are observed with regard to PrPSc deposition and stability of the prion aggregates.
Discussion
In humans, different prion types are linked with clinically and neuropathologically distinct prion diseases.8 The present work emphasizes that the differences in deposition characteristics and stability with regard to denaturation between atypical/Nor98 and classical scrapie also account for different prion types. Moreover, the two scrapie types that have been characterized show a number of striking similarities with human PrPSc types in sporadic CJD. Hence, we propose that the existence of different PrPSc types might be a common denominator of prion diseases in humans and animals. Since these two prion types show an across-the-species comparability with similar biochemical and pathological characteristics, it is most likely that they exist due to a different conformational pattern of the disease-related prion protein.
Prion Types Depend on Conformation
The interpretation that the conformation of PrPSc accounts for prion types is supported by different proteinase K-cleavage sites of human prion types9 and the propagation of mutation-associated prion characteristics in human transgenic mice without PRNP-point mutation. 31 However, differences in protein stability as they have been found in this study, provide direct evidence for a conformational distinction between these molecules.32 Further support for the relation between type and conformation is also given by experiments focusing on the size of prion protein aggregates. Using virus removal filters, Kobayashi et al33 were able to show differences in the size of CJD type 1 and type 2 aggregates: PrPSc type 2 forms larger aggregates than PrPSc type 1, independent of whether the disease was sporadic, iatrogenic or acquired. This difference is clearly reflected by the morphology of the PrPSc depositions we have found in sheep scrapie and human CJD. Sporadic CJD type 1 and atypical/ Nor98 scrapie are characterized by fine (reticular) deposits, whereas CJD type 2 and classical scrapie display a complex aggregate pattern, regardless of the respective genotypes at the polymorphic positions of the PRNP that were investigated.
Prion Type Characteristics Versus Prion Strain Characteristics
Structural differences of the disease-associated protein have also been proposed as an explanation for the existence of strains. Partial digestion of the disease-associated protein with proteinase K as well as differences in antibody binding after the protein was partially denatured were used to identify structural characteristics in correlation with strain properties and different clinical TSE forms.23,34,35 It needs to be considered that the kinetics of proteinase K-digestion of PrPSc are markedly influenced by detergent effects in the buffer, demonstrating that the accessibility of the cleavage sites are variable.35 In contrast, differences in the stability against total unfolding of PrPSc seem to be a usable criterion to identify conformational differences or conformational motives. Whereas detergents affect the tertiary structure of a protein by interacting with hydrophilic and hydrophobic areas of protein molecules, chaotropic salts like GdnHCl destroy the hydrogen bonds in -helices and -sheets leading to an irregular coiled polypeptide chain.36 This is in line with the observation that detergents remove prion infectivity only partially, whereas chemicals that destroy secondary structures like chaotropic salts are highly effective. 37 However, detectable differences regarding the stability against denaturation with GdnHCl shown for various prion strains in hamsters seem to be very small compared with the ones that can be shown here for the prion types of human and ovine prion diseases. Strains could thus correspond to structural differences that are less marked than those defining types and are probably constant only under defined conditions. Influences of polymorphisms or interactions with other genetic factors like the promotor region, species-specific factors like the recently detected incorporation of polyanionic molecules into prions,38 glycosaminoglycans or other yet unknown factors of the original host may also lead to different strains in a new host within the prion types of the original species.5,39 The existence of prion types does not exclude the existence of strains. The same variations that account for strains might be the reason for differences in the clinical disease course of the natural host.
Two Different Prion Types also in BSE?
Parallel to human sporadic CJD and our results in sheep scrapie, there is increasing evidence that two prion types also exist in cattle BSE. Two presumably sporadic forms of BSE known as H-type BSE14 and bovine amyloidotic spongiform encephalopathy, also called L-type BSE,15 have been described in cattle in addition to typical/classical BSE.40 The small variation in the apparent molecular weight of the unglycosylated band of bovine amyloidotic spongiform encephalopathy is considered to be well within the range of classical BSE,41,42 which would leave H-type BSE with a considerably larger unglycosylated fragment in Western blot analysis than the second BSE type. Interestingly, bovine amyloidotic spongiform encephalopathy converts into classical BSE after serial passages in bovine-transgenic mice,43 although displaying clinically different diseases in cattle.44 From the latter experiment the authors concluded that different strains were responsible for different phenotypes. Obviously the different clinical diseases were generated by agents that belong to a single prion type. These results together with our observations emphasize the need to differentiate strictly between prion types and prion strains and demonstrate that even in cattle BSE, one prion type may contain different prion strains.
Prion Type Displays Parallels in the Pathophysiology of Disease between Species
Biochemical and morphological similarities have been used to draw parallels between forms of BSE and human prion diseases.15 Parallels between species can also be observed with regard to the route of prion infection: in classical BSE, variant CJD, and classical scrapie, all of which presumably belong to one class of prion type (type 2 in humans) according to the observations made above, the oral route of infection has been identified. These TSEs use the dorsal motor nucleus of the vagus nerve as an entry site into the brain.29,45,46 This observation suggests that distinct prion types in human and animal TSEs possibly have an impact on the pathogenesis of prion diseases.
Conclusion
As the prion protein is a highly conserved protein in terms of evolution, parallels between characteristics of prion types in TSEs of different species are of interest. In the present study, we report previously unknown similarities between sheep scrapie forms and human sporadic CJD types. We propose that the observed similarities between sheep scrapie and sporadic CJD in humans justify new interspecies groups of prion diseases in which prion types, not prion strains, are the major determinant for prion disease forms. While epidemiology implies that classical scrapie is not related to human TSEs,47 the atypical/Nor98 scrapie risk for human transmission has not yet been elucidated. Currently there is no compelling evidence that sCJD has a different origin than sporadic genesis. However, the finding of prion types with an across-the-species comparability might provide further understanding of the pathogenesis in prion diseases.
Acknowledgments We thank Tatjana Pfander, Nadine Rupprecht, and Kerstin Brekerbohm for their skillful technical assistance.
http://ajp.amjpathol.org/cgi/content/abstract/175/6/2566
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
P.5.21
Parallels between different forms of sheep scrapie and types of Creutzfeldt-Jakob disease (CJD)
Wiebke M. Wemheuer1, Sylvie L. Benestad2, Arne Wrede1, Wilhelm E. Wemheuer3, Tatjana Pfander1, Bjørn Bratberg2, Bertram Brenig3,Walter J. Schulz-Schaeffer1 1University Medical Center Goettingen, Germany; 2Institute of Veterinary Medicine Oslo, Norway; 3Institute of Veterinary Medicine Goettingen, Germany
Background: Scrapie in sheep and goats is often regarded as the archetype of prion diseases. In 1998, a new form of scrapie – atypical/Nor98 scrapie – was described that differed from classical scrapie in terms of epidemiology, Western blot profile, the distribution of pathological prion protein (PrPSc) in the body and its stability against proteinase K. In a similar way, distinct disease types exist in sporadic Creutzfeldt-Jakob disease (CJD). They differ with regard to their clinical outcome, Western blot profile and PrPSc deposition pattern in the central nervous system (CNS).
Objectives: The comparison of PrPSc deposits in sheep scrapie and human sporadic CJD.
Methods: Tissues of the CNS of sheep with classical scrapie, sheep with atypical/Nor98 scrapie and 20 patients with sporadic CJD were examined using the sensitive Paraffin Embedded Tissue (PET) blot method. The results were compared with those obtained by immunohistochemistry. With the objective of gaining information on the protein conformation, the PrPSc of classical and atypical/Nor98 sheep scrapie and sporadic CJD was tested for its stability against denaturation with guanidine hydrochloride (GdnHCl) using a Membrane Adsorption Assay.
Results: The PrPSc of atypical/Nor98 scrapie cases and of CJD prion type 1 patients exhibits a mainly reticular/synaptic deposition pattern in the brain and is relatively sensitive to denaturation with GdnHCl. In contrast classical scrapie cases and CJD prion type 2 patients have a more complex PrPSc deposition pattern in common that consists of larger PrPSc aggregates and the PrPSc itself is comparatively stable against denaturation.
Discussion: The similarity between CJD types and scrapie types indicates that at least two comparable forms of the misfolded prion protein exist beyond species barriers and can elicit prion diseases. It seems therefore reasonable to classify classical and atypical/Nor98 scrapie – in analogy to the existing CJD types – as different scrapie types.
http://www.prion2009.com/sites/default/files/Prion2009_Book_of_Abstracts.pdf
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 1, 2008
When Atypical Scrapie cross species barriers
http://nor-98.blogspot.com/2008/12/when-atypical-scrapie-cross-species.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
Tuesday, April 28, 2009
Nor98-like Scrapie in the United States of America
http://nor-98.blogspot.com/2009/04/nor98-like-scrapie-in-united-states-of.html
Scrapie USA
http://scrapie-usa.blogspot.com/
Like lambs to the slaughter
31 March 2001
by Debora MacKenzie Magazine issue 2284
FOUR years ago, Terry Singeltary watched his mother die horribly from a degenerative brain disease. Doctors told him it was Alzheimer's, but Singeltary was suspicious. The diagnosis didn't fit her violent symptoms, and he demanded an autopsy. It showed she had died of sporadic Creutzfeldt-Jakob disease.
Most doctors believe that sCJD is caused by a prion protein deforming by chance into a killer. But Singeltary thinks otherwise. He is one of a number of campaigners who say that some sCJD, like the variant CJD related to BSE, is caused by eating meat from infected animals. Their suspicions have focused on sheep carrying scrapie, a BSE-like disease that is widespread in flocks across Europe and North America.
Now scientists in France have stumbled across new evidence that adds weight to the campaigners' fears. To their complete surprise, the researchers found that one strain of scrapie causes the same brain damage in ...
http://www.newscientist.com/article/mg16922840.300-like-lambs-to-the-slaughter.html
R.I.P. MOM hvCJD confirmed DECEMBER 14, 1997
TSS
Monday, December 1, 2008
When Atypical Scrapie cross species barriers
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 USA
INFECTED AND SOURCE FLOCKS
There were 20 scrapie infected and source flocks with open statuses (Figure 3) as of April, 30, 2008. Twenty eight new infected and source flocks have been designated in FY 2008 (Figure 4); three source flocks were reported in April. ...snip
POSITIVE SCRAPIE CASES
As of April 30, 2008, 122 new scrapie cases have been confirmed and reported by the National Veterinary Services Laboratories (NVSL) in FY 2008 (Figure 6). Of these, 103 were field cases and 19* were Regulatory Scrapie Slaughter Surveillance (RSSS) cases (collected in FY 2008 and reported by May 20, 2008). Positive cases reported for April 2008 are depicted in Figure 7. Eighteen 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 in February 2008 and originated from the same herd in Michigan as the other FY 2008 goat cases. ...snip
CAPRINE SCRAPIE PREVALENCE STUDY (CSPS)
snip...
However, four positive goats have been identified this fiscal year through field investigations. One was a clinical suspect submitted for testing and the other three originated from the birth herd of the clinical case.
ANIMALS SAMPLED FOR SCRAPIE TESTING
As of April 30, 2008, 26,703 animals have been sampled for scrapie testing: 23,378 RSSS, 1,517 goats for the CSPS study, 1,466 regulatory field cases, 270 regulatory third eyelid biopsies, and 72 regulatory rectal biopsies (chart 8).
TESTING OF LYMPHOID TISSUE OBTAINED BY RECTAL BIOPSY WAS APPROVED BY USDA AS AN OFFICIAL LIVE-ANIMAL TEST ON JANUARY 11, 2008. ...
PLEASE NOTE, (FIGURE 6), Scrapie Confirmed Cases in FY 2008 MAP, PA 3, 1**, Two cases-state of ID UNKNOWN, 1 case Nor98-like**
http://www.aphis.usda.gov/animal_health/animal_diseases/scrapie/downloads/monthly_scrapie_rpt.pps
http://scrapie-usa.blogspot.com/
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
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.
Edited by Stanley B. Prusiner, University of California, San Francisco, CA, and approved September 12, 2005 (received for review March 21, 2005)
http://www.pnas.org/cgi/content/abstract/0502296102v1
NOR-98 ATYPICAL SCRAPIE 5 cases documented in USA in 5 different states USA 007
http://nor-98.blogspot.com/2008/04/seac-spongiform-encephalopathy-advisory.html
Tuesday, June 3, 2008 SCRAPIE USA UPDATE JUNE 2008 NOR-98 REPORTED PA
http://nor-98.blogspot.com/2008/06/scrapie-usa-update-june-2008-nor-98.html
http://nor-98.blogspot.com/
TSS
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 USA
INFECTED AND SOURCE FLOCKS
There were 20 scrapie infected and source flocks with open statuses (Figure 3) as of April, 30, 2008. Twenty eight new infected and source flocks have been designated in FY 2008 (Figure 4); three source flocks were reported in April. ...snip
POSITIVE SCRAPIE CASES
As of April 30, 2008, 122 new scrapie cases have been confirmed and reported by the National Veterinary Services Laboratories (NVSL) in FY 2008 (Figure 6). Of these, 103 were field cases and 19* were Regulatory Scrapie Slaughter Surveillance (RSSS) cases (collected in FY 2008 and reported by May 20, 2008). Positive cases reported for April 2008 are depicted in Figure 7. Eighteen 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 in February 2008 and originated from the same herd in Michigan as the other FY 2008 goat cases. ...snip
CAPRINE SCRAPIE PREVALENCE STUDY (CSPS)
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However, four positive goats have been identified this fiscal year through field investigations. One was a clinical suspect submitted for testing and the other three originated from the birth herd of the clinical case.
ANIMALS SAMPLED FOR SCRAPIE TESTING
As of April 30, 2008, 26,703 animals have been sampled for scrapie testing: 23,378 RSSS, 1,517 goats for the CSPS study, 1,466 regulatory field cases, 270 regulatory third eyelid biopsies, and 72 regulatory rectal biopsies (chart 8).
TESTING OF LYMPHOID TISSUE OBTAINED BY RECTAL BIOPSY WAS APPROVED BY USDA AS AN OFFICIAL LIVE-ANIMAL TEST ON JANUARY 11, 2008. ...
PLEASE NOTE, (FIGURE 6), Scrapie Confirmed Cases in FY 2008 MAP, PA 3, 1**, Two cases-state of ID UNKNOWN, 1 case Nor98-like**
http://www.aphis.usda.gov/animal_health/animal_diseases/scrapie/downloads/monthly_scrapie_rpt.pps
http://scrapie-usa.blogspot.com/
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
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.
Edited by Stanley B. Prusiner, University of California, San Francisco, CA, and approved September 12, 2005 (received for review March 21, 2005)
http://www.pnas.org/cgi/content/abstract/0502296102v1
NOR-98 ATYPICAL SCRAPIE 5 cases documented in USA in 5 different states USA 007
http://nor-98.blogspot.com/2008/04/seac-spongiform-encephalopathy-advisory.html
Tuesday, June 3, 2008 SCRAPIE USA UPDATE JUNE 2008 NOR-98 REPORTED PA
http://nor-98.blogspot.com/2008/06/scrapie-usa-update-june-2008-nor-98.html
http://nor-98.blogspot.com/
TSS
Friday, July 18, 2008
TSE risk assessment from carcasses of ovine and caprine animals below 6 months of age from TSE infected flocks intended for human consumption
TSE risk assessment from carcasses of ovine and caprine animals below 6 months of age from TSE infected flocks intended for human consumption - Scientific Opinion of the Panel on Biological Hazards Question number: EFSA-Q-2007-202
Adopted date: 05/06/2008 Summary (0.1Mb)
Opinion (0.2Mb)
Summary
Following a request from the European Commission, the Panel on Biological Hazards (BIOHAZ) was asked to deliver a scientific Opinion on a TSE risk assessment from carcasses of ovine and caprine animals below 6 months of age from TSE infected flocks intended for human consumption. Its terms of reference were as follows: to provide an assessment on the existence of a significant additional risk to human health compared with the actual situation, founded on the scientific evidences, from the consumption of carcasses from ovine or caprine animals below 6 months of age from TSE affected flocks (without been subjected to a TSE rapid test and irrespectively of the genotype) provided that the entire head and the viscera of the thoracic and abdominal cavities are removed and excluded from human consumption and provided that BSE is excluded (in the outbreak) according to the procedure laid down in 3.2 (c), Chapter C of Annex X to the Regulation (EC) 999/2001. After clarification from the Commission, the BIOHAZ Panel was able to refine the ToR to focus on the change of human exposure that might result from the proposed change of risk management procedure and that it specifically required an estimate of the relative levels of TSE infectivity in the carcass of a lamb or kid less than 3 months of age from which spleen and ileum have been removed, compared to the carcass of a lamb or kid less than 6 months of age from which the spleen, the ileum, the head and the viscera of the abdominal and thoracic cavity have been removed. In answer to these ToR, the BIOHAZ Panel concluded: A quantitative comparison of infectivity load in both scenarios is not possible, because there are no data available on the amount of infectious tissues that would be still present on the carcasses of 3 months and 6 months of age of lambs and kids, prepared according to the terms of reference (i.e. 3 months with head and viscera from the thoracic and abdominal cavity remaining for human consumption, but excluding the spleen and the ileum which is currently removed as Specified Risk Material; 6 months of age without head and all the viscera from the thoracic and abdominal cavities). There is an increase, between 3 and 6 months of age, of the number of PrPres accumulating lymphoid formations. A part of these newly involved lymphoid formations would remain on dressed carcasses. In the worst case scenario, there would be an increase in infectivity level in lymphoid tissue between ages of 3 and 6 months (approximately 10 fold) on a per unit weight basis. The level of infectivity in secondary lymphoid tissues that may remain on the dressed carcasses, can reach by 6 months of age a level of infectivity per gram equivalent to 1/50 of that found in the same amount of brain tissue from a terminally affected sheep. Removal of the head and the thoracic and abdominal viscera will result in incomplete removal of the infectivity load at both 3 and 6 months of age. In the absence of new quantitative data on the tissue infectivity load in kids and lambs, the risk assessment and procedures for safe sourcing of small ruminant materials proposed in 2002 by the SSC, including the use of the combination of genotype and age as sourcing criteria, remain valid. The BIOHAZ Panel further recommends that to facilitate future attempts at quantitative risk assessments in this field, more experimental work is needed to define the variability and uncertainty of both the estimates of relative infectivity titre at different ages in young lambs and kids and of the weights of lymphoid tissue entering the food chain.
Publication date: 15/07/2008
http://www.efsa.europa.eu/EFSA/efsa_locale-1178620753812_1178720552868.htm
TSE risk assessment from carcasses of ovine and caprine animals below 6 months of age from TSE infected flocks intended for human consumption Scientific Opinion of the Panel on Biological Hazards (Question No EFSA-Q-2007-202) Adopted on 5 June 2008 SUMMARY Following a request from the European Commission, the Panel on Biological Hazards (BIOHAZ) was asked to deliver a scientific Opinion on a TSE risk assessment from carcasses of ovine and caprine animals below 6 months of age from TSE infected flocks intended for human consumption. Its terms of reference were as follows: to provide an assessment on the existence of a significant additional risk to human health compared with the actual situation, founded on the scientific evidences, from the consumption of carcasses from ovine or caprine animals below 6 months of age from TSE affected flocks (without been subjected to a TSE rapid test and irrespectively of the genotype) provided that the entire head and the viscera of the thoracic and abdominal cavities are removed and excluded from human consumption and provided that BSE is excluded (in the outbreak) according to the procedure laid down in 3.2 (c), Chapter C of Annex X to the Regulation (EC) 999/2001. After clarification from the Commission, the BIOHAZ Panel was able to refine the ToR to focus on the change of human exposure that might result from the proposed change of risk management procedure and that it specifically required an estimate of the relative levels of TSE infectivity in the carcass of a lamb or kid less than 3 months of age from which spleen and ileum have been removed, compared to the carcass of a lamb or kid less than 6 months of age from which the spleen, the ileum, the head and the viscera of the abdominal and thoracic cavity have been removed. In answer to these ToR, the BIOHAZ Panel concluded: • A quantitative comparison of infectivity load in both scenarios is not possible, because there are no data available on the amount of infectious tissues that would be still present on the carcasses of 3 months and 6 months of age of lambs and kids, prepared according to the terms of reference (i.e. 3 months with head and viscera from the thoracic and abdominal cavity remaining for human consumption, but excluding the spleen and the ileum which is currently removed as Specified Risk Material; 6 months of age without head and all the viscera from the thoracic and abdominal cavities). • There is an increase, between 3 and 6 months of age, of the number of PrPres accumulating lymphoid formations. A part of these newly involved lymphoid formations would remain on dressed carcasses. • In the worst case scenario, there would be an increase in infectivity level in lymphoid tissue between ages of 3 and 6 months (approximately 10 fold) on a per unit weight basis. Summary of opinion The EFSA Journal (2008) 719, 2-2 • The level of infectivity in secondary lymphoid tissues that may remain on the dressed carcasses, can reach by 6 months of age a level of infectivity per gram equivalent to 1/50 of that found in the same amount of brain tissue from a terminally affected sheep. • Removal of the head and the thoracic and abdominal viscera will result in incomplete removal of the infectivity load at both 3 and 6 months of age. • In the absence of new quantitative data on the tissue infectivity load in kids and lambs, the risk assessment and procedures for safe sourcing of small ruminant materials proposed in 2002 by the SSC, including the use of the combination of genotype and age as sourcing criteria, remain valid. The BIOHAZ Panel further recommends that to facilitate future attempts at quantitative risk assessments in this field, more experimental work is needed to define the variability and uncertainty of both the estimates of relative infectivity titre at different
http://www.efsa.europa.eu/EFSA/Scientific_Opinion/biohaz_op_ej719_tse_carcasses_smru_summary_en.pdf
TSE risk assessment from carcasses of ovine and caprine animals below 6 months of age from TSE infected flocks intended for human consumption 1 Scientific Opinion of the Panel on Biological Hazards (Question No EFSA-Q-2007-202) Adopted on 5 June 2008
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CONCLUSIONS
1. General conclusions: • Lambs and kids from TSE affected flocks in the form of classical scrapie have a clearly higher probability of infection than those from the general population. In the general EU sheep population TSE prevalence at animal level is estimated to be about 0.1 %. In classical scrapie affected sheep flocks the reported prevalence vary from 3% to 41%. • In susceptible lambs (VRQ/VRQ), infectivity will replicate in lymphoid tissues from birth and involve most secondary lymphoid formations before 4 months old. • In worst cases, infectivity in lymphoid organs reaches its maximal level before 6 months old. This maximal level infectivity in lymphoid organs (per mass unit) can be estimated to be about 1/50 of the infectivity found in obex from a terminally affected ewe. • According to currently available data, carcasses of animals of less than two months of age, providing that the head and the thoracic and abdominal viscera are removed, do not contain detectable PrPres but this does not exclude the possibility of infectivity.
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APPENDIX II. FURTHER DATA RELEVANT TO THE TIMING AND SPREAD OF INFECTION IN VRQ/VRQ LAMBS
a. Colostrum/Milk as a potential source of infectivity. Qualitative TSE risk assessments of the safety of milk from sheep and goats have been made in the past, but little published data have been available. Konold and colleagues have recently published a study of the transmission of scrapie from scrapie-affected dams to lambs by feeding from birth milk (and colostrum) taken during the later stages of scrapie-infection in the dams (Konold et al., 2008). Evidence of infection was detected as early as 44-46 days in the distal ileum of two lambs by immunohistochemistry for abnormal PrP (PrPres) and widespread infection inferred by RAMALT6 testing by 190-210 days of age. Both donor ewes and lambs were of the susceptible VRQ/VRQ genotype and the donor ewes were sourced from a flock with a ~ 10% prevalence of natural infection. This is directly relevant to the consideration of “a worst case scenario” and confirms previous work indicating lambs can become infected very soon after birth and that, within 6-7 months, the infection can be widely disseminated, at least in lymphoid tissue, in the susceptible animal.
b. The role of blood in spreading the agent within the body. One of the critical scientific uncertainties (for any naturally occurring TSE in any species) is that related to the possibility of infectivity in blood. Information on the incubation stage(s) wherein this happens is meagre and it is not yet known if this is an inconsistent chance event or an important way in which the pathogen spreads within the body. The data published by Houston et al. (2000) and Hunter et al. (2002) showed that a high volume blood transfusion from sheep to sheep can transmit BSE as well as scrapie within the same species. With both diseases, infectivity could also be transmitted using blood taken during the asymptomatic incubation period of the disease in the donor sheep. In the specific context of this mandate, Andreoletti and co-workers have reported infectivity in blood of pre-clinical VRQ/VRQ lambs at 3 months of age (Andreoletti et al., Neuroprion Edinburgh 2007).
c. Intestine: the anatomical location where infectivity is first detected. PrPres in the digestive tract has been described in sheep exposed to natural scrapie (van Keulen et al., 1999; Andreoletti et al., 2000). Most of the data available were obtained in natural scrapie and the prion protein genotype of the sheep is a critical factor in the uptake and dissemination of the agents of BSE and scrapie in the gut of the sheep. In VRQ/VRQ sheep exposed to natural scrapie infection, PrPres can be detected in ileal Peyer’s patches (PP) from 21 days post-partum and in other PP’s of the alimentary canal and in the tonsil of the lamb by 60 days of age. In similar conditions, PrPres is detectable in the enteric nervous system (ENS) at 7 months old, almost three months prior to its first detection in the obex (Andreoletti et al., 2000). Hence, during surveillance, screening the obex using rapid testing for PrPres is a poor indicator for the absence of TSE infection in the digestive tract of the lamb. 6 RAMALT stands for recto-anal mucosal associated lymphoid tissue.
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http://www.efsa.europa.eu/EFSA/Scientific_Opinion/biohaz_op_ej719_tse_carcasses_smru_en.pdf
OPINION ON SAFE SOURCING OF SMALL RUMINANT MATERIALS (SAFE SOURCING OF SMALL RUMINANT MATERIALS SHOULD BSE IN SMALL RUMINANTS BECOME PROBABLE: GENOTYPE, BREEDING, RAPID TSE TESTING, FLOCKS CERTIFICATION AND SPECIFIED RISK MATERIALS) ADOPTED BY THE SCIENTIFIC STEERING COMMITTEE AT ITS MEETING OF 4-5 APRIL 2002
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III.1.2. As for BSE in sheep, research data are available for only a few tens of animals: - Results to date indicate that the relation between sheep genotype and susceptibility to a TSE is similar for scrapie and BSE: the ARR genotypes are apparently resistant to development of clinical disease on challenge with BSE and animals carrying the glutamine (Q) allele at codon 171 are potentially susceptible to BSE and to scrapie. The influence of the genotype at codon 136 and 154 is not yet known for BSE but is being tested by direct challenge studies at IAH, UK. - New research data summarised in EC (2002) are consistent with the previously expressed view that BSE in sheep after oral exposure is pathogenetically closely similar to scrapie, particularly with respect to the tissue distribution of infectivity and/or PrPSc.
page 17 of 69...snip...end
http://ec.europa.eu/food/fs/sc/ssc/out257_en.pdf
ISSUE All Member States are required to produce a contingency plan in the event BSE were found in sheep.
The UK is currently finalising its detailed plan, for submission to the Commission this summer. The European Commission has recently produced guidelines for Member States on the points which should be considered in drawing up their contingency plans. (Annex 1). The guidelines suggest that Member States should consider a worst case scenario where sheep meat is excluded from the food chain. This is based on an opinion, adopted by the Scientific Steering Committee (SSC) in April 2002, entitled “Safe sourcing of small ruminant materials” (Annex 2). The SSC Opinion states that if BSE were found in sheep, then only the following animals should be allowed into the food chain: • ARR homozygous sheep under the age of 18 months • ARR heterozygous sheep under the age of 6 months. • Sheep (and goat) milk, colostrum and milk products from suspect BSE cases should be excluded from the food chain. The EC guidelines (SANCO/19/2003 Rev.2) state a worst case scenario where: • small ruminant meat is excluded from the food chain unless derived from: - homozygous ARR sheep under the age of 18 months - heterozygous sheep under the age of 6 months • sheep and goat milk is excluded from the food and feed chain: - completely, or - unless derived from sheep carrying at least one ARR allele, or - unless derived from holdings certified TSE resistant or TSE free on the basis of solid criteria. They should also make an inventory of their capacity in terms of genotyping, individual identification and registration of animals, TSE testing and in terms of flock certification on the basis of history, monitoring etc.
CONFIDENTIAL PAPER No: SEAC 78/9 Amendment 2 2 In March 2002, a SEAC Sub-Group considered the risks associated with certain genotypes entering the food chain if BSE were ever isolated from sheep. In contrast to the SSC opinion, SEAC concluded that: • In line with previous SEAC advice, only animals carrying the ARR allele should enter the food chain • On a precautionary basis, the 12 month cut off previously advised by SEAC remained appropriate for ARR heterozygotes. However, in view of existing SRM regulations there was no justification for any age cut off in ARR homozygotes • In line with SEAC advice in 2001, only milk from ARR homozygous sheep could be considered as highly unlikely to contain the infectious agent. Further experimental work was required before potential risks from small ruminant milk from goats and semi-resistant or susceptible sheep could be excluded. There is therefore a disparity of opinion between the SSC and SEAC on this issue. Whilst recognising the uncertainties relating to the science in this area, it is important that contingency planning is based on the most up to date scientific developments and assessments of risk that are available. SEAC will be presented with an update on the ongoing BSE in sheep studies, funded by Defra (Annex 31). This covering paper also provides a history of previous SEAC advice on this issue. BACKGROUND...snip...end
http://www.seac.gov.uk/papers/78-9-closed.pdf
12/10/76 AGRICULTURAL RESEARCH COUNCIL REPORT OF THE ADVISORY COMMITTE ON SCRAPIE Office Note CHAIRMAN: PROFESSOR PETER WILDY
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A The Present Position with respect to Scrapie 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 is 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 emphasized by the finding that some strains of scrapie produce lesions identical to the once which characterize the human dementias"
Whether true or not. the hypothesis that these agents might be transmissible to man raises two considerations. First, the safety of laboratory personnel requires prompt attention. Second, action such as the "scorched meat" policy of USDA makes the solution of the scrapie problem urgent if the sheep industry is not to suffer grievously.
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76/10.12/4.6
http://www.bseinquiry.gov.uk/files/yb/1976/10/12004001.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.
PMID: 6997404
http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=6997404&ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstractPlus
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://www.bseinquiry.gov.uk/files/yb/1994/02/07002001.pdf
Like lambs to the slaughter
31 March 2001 Debora MacKenzie Magazine issue 2284
What if you can catch old-fashioned CJD by eating meat from a sheep infectedwith scrapie?FOUR years ago, Terry Singeltary watched his mother die horribly from adegenerative brain disease. Doctors told him it was Alzheimer's, butSingeltary was suspicious. The diagnosis didn't fit her violent symptoms,and he demanded an autopsy. It showed she had died of sporadicCreutzfeldt-Jakob disease.
Most doctors believe that sCJD is caused by a prion protein deforming bychance into a killer. But Singeltary thinks otherwise. He is one of a numberof campaigners who say that some sCJD, like the variant CJD related to BSE,is caused by eating meat from infected animals. Their suspicions havefocused on sheep carrying scrapie, a BSE-like disease that is widespread inflocks across Europe and North America.
Now scientists in France have stumbled across new evidence that adds weightto the campaigners' fears. To their complete surprise, the researchers foundthat one strain of scrapie causes the same brain damage in ...
The complete article is 889 words long.
full text;
http://www.newscientist.com/article/mg16922840.300-like-lambs-to-the-slaughter.html
Neurobiology Adaptation of the bovine spongiform encephalopathy agent to primates and comparison with Creutzfeldt-Jakob disease: Implications for human health
Corinne Ida Lasmézas*,, Jean-Guy Fournier*, Virginie Nouvel*, Hermann Boe*,Domíníque Marcé*, François Lamoury*, Nicolas Kopp, Jean-Jacques Hauw§, JamesIronside¶, Moira Bruce, Dominique Dormont*, and Jean-Philippe Deslys** Commissariat à l'Energie Atomique, Service de Neurovirologie, Directiondes Sciences du Vivant/Département de Recherche Medicale, Centre deRecherches du Service de Santé des Armées 60-68, Avenue du Général Leclerc,BP 6, 92 265 Fontenay-aux-Roses Cedex, France; Hôpital Neurologique PierreWertheimer, 59, Boulevard Pinel, 69003 Lyon, France; § Laboratoire deNeuropathologie, Hôpital de la Salpêtrière, 83, Boulevard de l'Hôpital,75013 Paris, France; ¶ Creutzfeldt-Jakob Disease Surveillance Unit, WesternGeneral Hospital, Crewe Road, Edinburgh EH4 2XU, United Kingdom; andInstitute for Animal Health, Neuropathogenesis Unit, West Mains Road,Edinburgh EH9 3JF, United Kingdom
Edited by D. Carleton Gajdusek, Centre National de la RechercheScientifique, Gif-sur-Yvette, France, and approved December 7, 2000(received for review October 16, 2000)
Abstract
There is substantial scientific evidence to support the notion that bovinespongiform encephalopathy (BSE) has contaminated human beings, causingvariant Creutzfeldt-Jakob disease (vCJD). This disease has raised concernsabout the possibility of an iatrogenic secondary transmission to humans,because the biological properties of the primate-adapted BSE agent areunknown. We show that (i) BSE can be transmitted from primate to primate byintravenous route in 25 months, and (ii) an iatrogenic transmission of vCJDto humans could be readily recognized pathologically, whether it occurs bythe central or peripheral route. Strain typing in mice demonstrates that theBSE agent adapts to macaques in the same way as it does to humans andconfirms that the BSE agent is responsible for vCJD not only in the UnitedKingdom but also in France. The agent responsible for French iatrogenicgrowth hormone-linked CJD taken as a control is very different from vCJD butis similar to that found in one case of sporadic CJD and one sheep scrapieisolate. These data will be key in identifying the origin of human cases ofprion disease, including accidental vCJD transmission, and could providebases for vCJD risk assessment.
http://www.pnas.org/cgi/content/full/041490898v1
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http://scrapie-usa.blogspot.com/2006/12/scrapie-usa.html
Saturday, December 08, 2007 SCRAPIE HB Parry Seriously’ (YB88/6.8/4.1)
HB Parry Seriously’ (YB88/6.8/4.1)
IF the scrapie agent is generated from ovine DNA and thence causes disease in other species, then perhaps, bearing in mind the possible role of scrapie in CJD of humans (Davinpour et al, 1985), scrapie and not BSE should be the notifiable disease.
http://www.bseinquiry.gov.uk/files/yb/1988/06/08004001.pdf
1: Neuroepidemiology. 1985;4(4):240-9.
Sheep consumption: a possible source of spongiform encephalopathy in humans.
Davanipour Z, Alter M, Sobel E, Callahan M.
A fatal spongiform encephalopathy of sheep and goats (scrapie) shares many characteristics with Creutzfeldt-Jakob disease (CJD), a similar dementing illness of humans. To investigate the possibility that CJD is acquired by ingestion of contaminated sheep products, we collected information on production, slaughtering practices, and marketing of sheep in Pennsylvania. The study revealed that sheep were usually marketed before central nervous system signs of scrapie are expected to appear; breeds known to be susceptible to the disease were the most common breeds raised in the area; sheep were imported from other states including those with a high frequency of scrapie; use of veterinary services on the sheep farms investigated and, hence, opportunities to detect the disease were limited; sheep producers in the area knew little about scrapie despite the fact that the disease has been reported in the area, and animal organs including sheep organs were sometimes included in processed food. Therefore, it was concluded that in Pennsylvania there are some 'weak links' through which scrapie-infected animals could contaminate human food, and that consumption of these foods could perhaps account for spongiform encephalopathy in humans. The weak links observed are probably not unique to Pennsylvania.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3915057&dopt=Abstract
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Scrapie has been transmitted in our laboratory to five species of monkeys (Tables 9 and 10) (23, 31, 32), and such transmission has occurred using infected brain from naturally infected sheep and from experimentally infected goats and mice (Figures 22a, b, c). The disease produced is clinically and pathologically indistinguishable from experimental CJD in these species. .........
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22b. Primary transmission of goat-adapted scrapie (Compton, England strain) to the squirrel monkey and to mice and the transmission of mouse-adapted scrapie to two species of Old World and three species of New World monkeys. Numbers in parentheses are the number of months elapsed since inoculation, during which the animal remained asymptomatic.
SNIP...
22c. Transmission of mouse-adapted sheep scrapie (U. S. strain 434-3-897) to a squirrel monkey 38 months following intracerebral inoculation with a suspension of scrapie-infected mouse brain containing 10a7.3 infectious units of virus per ml. This animal showed signs of ataxia, tremors and incoordination, and the disease was confirmed histologically. See (b) for an explanation of symbols.
SNIP...
Figure 23. Transmissible mink encephalopathy (TME), a rare disease of American ranch mink, is possibly a form of scrapie. The clinical picture and histopathological lesions attendant in the brain, resemble that of scrapie, and scrapie sheep carcasses were fed to mink on ranches on which TME appeared. The disease is transmissible to sheep, goats, certain rodents and New and Old World monkeys. Illustrative data on the primary transmissions of transmissible mink encephalopathy to one species of New World monkey and two species of Old World monkeys, and serial passage of the virus in squirrel, rhesus and stumptailed monkeys are presented in this Figure. Incubation periods are shown in months that elapsed between inoculation and onset of clinical disease. (Figure includes information from our laboratory and from R. F. Marsh, R. J. Eckroade, and R. P. Hanson.)
SNIP... end
SOURCE;
UNCONVENTIONAL VIRUSES AND THE ORIGIN
AND DISAPPEARANCE OF KURU
Nobel Lecture, December 13, 1976
by D. CARLETON GAJDUSEK
National Institutes of Health, Bethesda, Maryland, U.S.A.
snip... see ;
http://scrapie-usa.blogspot.com/2007/12/scrapie-hb-parry-seriously-yb886841.html
Monday, December 24, 2007 Pathogenesis of bovine spongiform encephalopathy in sheep
http://scrapie-usa.blogspot.com/2007/12/pathogenesis-of-bovine-spongiform.html
Friday, February 15, 2008 SCRAPIE and TSE to human UPDATE 2008 (ambiguous terms of transition and reality set in)
snip...
2. In relation to conclusion 2 in page 7 the Authority is invited to specify the scientific evidences which do not allow to exclude transmissibility to humans of “other TSE agents” other than BSE. Conclusion 2 in page 7 of the EFSA 2007 opinion states that: “The BSE agent is the only TSE agent identified as zoonotic. However, in view of their diversity it is currently not possible to exclude transmissibility to humans of other animal TSE agents.”
In the EFSA 2007 opinion under 3.2.3. the Panel states that:
• “There are significant uncertainties associated with the question whether TSE agents in their whole spectrum may cross the human transmission barrier under natural conditions”.
This statement is supported both by scientific evidence and considerations, referenced in the EFSA 2007 opinion:
• Scientific evidence from transmission studies to primates: - Transmission of Classical Scrapie from a TSE agent adapted in hamster was demonstrated by oral challenge in squirrel monkey (Saimiri sciureus) (Gibbs et al., 1980);
- Transmission of Classical Scrapie from two distinct sheep sources by intracerebral challenge in cynomologus monkey (Macaca fascicularis) and marmoset monkey (Callithrix jacchus) (Gibbs and Gajdusek, 1972; Baker et al., 1988).
• Scientific considerations on TSE epidemiology: - “The assumed lack of association between TSEs in humans and those in small ruminants […] may be biased by a number of factors: (i) The lack of a data on the historical real prevalence and distribution of small ruminant TSEs, at a time where only passive surveillance was performed; (ii) the lack of understanding of the true biodiversity of TSEs in small ruminants in terms of both Classical and Atypical agents; (iii) the lack of understanding of the diversity of TSEs in humans due to the limited molecular and bioassay characterisation of human TSEs also in relation to the number and spectrum of neurodegenerative diseases of humans; (iv) the predicted phenotype of disease that might arise should an animal derived TSE transmit to humans.” The EFSA Journal (2008) 626, 5-11
Further evidence is provided by:
• In vitro conversion assays: Raymond et al. (1997) studied whether there is a correlation between in vitro conversion efficiencies and known transmissibility of BSE, sheep Scrapie and CJD, and found limited conversion of human PrP-sen to PrP-res driven by PrP-res associated with both Scrapie (PrPSc) and BSE (PrPBSE). They concluded that “the inherent ability of these infectious agents of BSE and Scrapie to affect humans following equivalent exposure may be finite but similarly low”. Nevertheless, uncertainty arises from the fact that this is a simple in vitro model of a complex in vivo situation.
• Laboratory transmission studies with animal models: Since the publication of the Opinion new data have become available with regards to L type of BSE, which has now been identified in various EU members states (Biacabe et al., 2004; Casalone et al., 2004; Baron et al., 2007). This TSE agent, differing from that causing Classical BSE by its biochemical signature and transmission features in mouse models, has been transmitted to a Tg mouse model expressing Human M129 PRP gene (Beringue et al. 2007)2. Here again, uncertainty arises from the limitations of these animal models for the estimation of the human species barrier. These ‘proof of principle’ experiments provide data supporting the ability of TSE agents other than those causing Classical BSE to cross the human species barrier.
Even so, it is important to remember that as mentioned in the EFSA 2007 opinion, transmission to primates:
• “… does not allow to take into account the human gene PRNP polymorphisms (in particular the M/V 129), that have been identified to play a major role on relative susceptibility towards prion disease. In addition, genes other than the PrP gene may also be influential in determining overall susceptibility to TSEs.” Despite the interests in the area, studies of the transmissibility of currently known TSE agents using animal models will remain incomplete for several years.
In conclusion, the reply to the ToR number 2 is:
• Experimental transmissions to primate and to transgenic (Tg) mouse models expressing the human PrP gene, are currently used as to evaluate the potential capacity of a TSE agent to cross the human species barrier.
• TSE agents other than the Classical BSE agent from three field TSE cases (two Classical Scrapie cases and one L type BSE case) have been demonstrated to cross the modelled human species barrier.
• Some limitations to these models have to be considered, which include:
(i) The uncertainty of how well they represent the human species barrier. (ii) The uncertainty of how well the experimental inoculation route employed represents exposure under natural conditions. 2 Transmission of this TSE agent by intracerebral challenge to primates (Macaques) has been reported by Comoy et al. at the 2006 Prion Congress held in Torino. A scientific paper reporting this finding has been submitted for peer review publication. The EFSA Journal (2008) 626, 6-11
snip...
http://ec.europa.eu/dgs/health_consumer/library/pub/pub07_en.pdf
EFSA 2005. Opinion of the Scientific Panel on Biological Hazards on the request from the European Commission on classification of Atypical Transmissible Spongiform Encephalopathy (TSE) cases in small ruminants. The EFSA Journal 276: 1-30.
http://www.efsa.europa.eu/EFSA/efsa_locale-1178620753812_1178620776235.htm
The EFSA Journal (2008) 626, 11-11
EFSA 2007. Opinion of the Scientific Panel on Biological Hazards on a request from the European Commission on certain aspects related to the risk of Transmissible Spongiform Encephalopathies (TSEs) in ovine and caprine animals. The EFSA Journal 466: 1-10.
http://www.efsa.europa.eu/EFSA/efsa_locale-1178620753812_1178620775196.htm
Date: September 26, 2007 at 4:06 pm PST
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.
http://www.prion2007.com/pdf/Prion%20Book%20of%20Abstracts.pdf
snip... see;
http://scrapie-usa.blogspot.com/2008/02/scrapie-and-tse-to-human-update-2008.html
Saturday, April 12, 2008 Evidence of scrapie transmission via milk
http://scrapie-usa.blogspot.com/2008/04/evidence-of-scrapie-transmission-via.html
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.
Edited by Stanley B. Prusiner, University of California, San Francisco, CA, and approved September 12, 2005 (received for review March 21, 2005)
http://www.pnas.org/cgi/content/abstract/0502296102v1
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
In FY 2007, 331 scrapie cases have been confirmed and reported by the National Veterinary Services Laboratories (NVSL), including 59* Regulatory Scrapie Slaughter Surveillance (RSSS) cases (Figure 5 and Slide 16). In FY 2007, two field cases, one validation case, and two RSSS cases were consistent with Nor-98 scrapie. The Nor98-like cases originated from flocks in California, Minnesota, Colorado, Wyoming and Indiana respectively. Nineteen cases of scrapie in goats have been reported since 1990 (Figure 6). The last goat case was reported in September 2007.
snip...
see full report here ;
http://www.aphis.usda.gov/animal_health/animal_diseases/scrapie/downloads/yearly_report.pps
http://nor-98.blogspot.com/2008/06/scrapie-usa-update-june-2008-nor-98.html
http://nor-98.blogspot.com/
now, confusious is confused again. why do some countries have their TSE reported on the OIE weekly listing of disease on the OIE website, but others like the USA, do not $$$
case in point ;
SCRAPIE PORTUGAL
Information received on 16/07/2008 from Mr Carlos Agrela Pinheiro, Chief Veterinary Officer, Director General, Direcçao-Geral de Veterinária, Ministério da Agricultura, LISBONNE, Portugal
http://www.oie.int/wahid-prod/public.php?page=single_report&pop=1&reportid=7201
Wednesday, June 11, 2008
OIE Recognition of the BSE Status of Members RESOLUTION No. XXI (Adopted by the International Committee of the OIE on 27 May 2008)
snip...
CONSIDERING THAT
1. Adoption of subsequent Resolutions* since the 67th General Session of the OIE International Committee has established a procedure for annually updating a list of Members, categorised by their BSE risk according to the provisions of theTerrestrial Code,
2. During the 70th General Session, the International Committee adopted Resolution No. XVIII asking Members applying for a BSE risk evaluation to meet part of the costs sustained by the OIE Central Bureau in the evaluation process,
3. During the 72nd General Session, the OIE adopted Resolution No. XXI requesting the Director General to inform Delegates of Members whose country or zones are recognised with regard to their BSE risk status should annually confirm during the month of November whether their risk status and the criteria by which their status was recognised have remained unchanged,
4. Information published by the OIE is derived from declarations made by the official Veterinary Services of Members. The OIE is not responsible for inaccurate publication of a Member disease status based on inaccurate information, changes in epidemiological status or other significant events that were not promptly reported to the Central Bureau, subsequent to the time of declaration of the BSE risk status.
THE COMMITTEE
RESOLVES THAT
1. The Director General publish the following list of Members recognised as having a negligible BSE risk in accordance with Chapter 2.3.13. of the Terrestrial Code:
Australia, Argentina, Finland, Iceland, New Zealand, Norway, Paraguay, Singapore, Sweden and Uruguay.
2. The Director General publish the following list of Members recognised as having a controlled BSE risk in accordance with Chapter 2.3.13. of the Terrestrial Code:
Austria Belgium Brazil Canada Chile Chinese Taipei Cyprus Czech Republic Denmark Estonia France Germany Greece Hungary Ireland Italy Latvia Lichtenstein Lithuania Luxembourg Malta Mexico Netherlands Poland Portugal Slovak Republic Slovenia Spain Switzerland United Kingdom United States of America
AND
3. The Delegates of these Members will immediately notify the Central Bureau if BSE occurs in their countries or their territories.
_________
(Adopted by the International Committee of the OIE on 27 May 2008)
* 67th General Session (GS) Resolution No (Res) XVI and Res XI; 69th GS Res XV, and 71st GS Res XXII, 72nd GS Res XXIV and Res XXI..
http://www.oie.int/eng/info/en_statesb.htm?e1d6
IN A NUT SHELL ;
(Adopted by the International Committee of the OIE on 23 May 2006)
11. Information published by the OIE is derived from appropriate declarations made by the official Veterinary Services of Member Countries. The OIE is not responsible for inaccurate publication of country disease status based on inaccurate information or changes in epidemiological status or other significant events that were not promptly reported to the Central Bureau,
http://www.oie.int/eng/Session2007/RF2006.pdf
snip...SEE FULL TEXT with facts and sources @ ;
http://usdavskorea.blogspot.com/2008/06/oie-recognition-of-bse-status-of.html
http://organicconsumers.org/forum/index.php?showtopic=1566
BSE BASE MAD COW TESTING TEXAS, USA, AND CANADA
http://madcowtesting.blogspot.com/
Attachment to Singeltary comment
January 28, 2007
Greetings APHIS,
I would kindly like to submit the following to ;
BSE; MRR; IMPORTATION OF LIVE BOVINES AND PRODUCTS DERIVED FROM BOVINES [Docket No. APHIS-2006-0041] RIN 0579-AC01
[Federal Register: January 9, 2007 (Volume 72, Number 5)] [Proposed Rules] [Page 1101-1129] From the Federal Register Online via GPO Access [wais.access.gpo.gov] [DOCID:fr09ja07-21]
http://www.regulations.gov/fdmspublic/component/main?main=DocumentDetail&o=09000064801f8152
BSE; MRR; IMPORTATION OF LIVE BOVINES AND PRODUCTS DERIVED FROM BOVINES [Docket No. APHIS-2006-0041] RIN 0579-AC01 Date: January 9, 2007 at 9:08 am PST
http://www.regulations.gov/fdmspublic/component/main?main=DocumentDetail&o=09000064801f3412
bottom line, you don't look, you dont find, you don't report, you dont have, thus, you have this imaginary classification called the BSE MRR 'CONTROLLED RISK' ;-)
THE REALITY IS ;
EFSA Scientific Report on the Assessment of the Geographical BSE-Risk (GBR) of the United States of America (USA)
Summary of the Scientific Report
The European Food Safety Authority and its Scientific Expert Working Group on the Assessment of the Geographical Bovine Spongiform Encephalopathy (BSE) Risk (GBR) were asked by the European Commission (EC) to provide an up-to-date scientific report on the GBR in the United States of America, i.e. the likelihood of the presence of one or more cattle being infected with BSE, pre-clinically as well as clinically, in USA. This scientific report addresses the GBR of USA as assessed in 2004 based on data covering the period 1980-2003.
The BSE agent was probably imported into USA and could have reached domestic cattle in the middle of the eighties. These cattle imported in the mid eighties could have been rendered in the late eighties and therefore led to an internal challenge in the early nineties. It is possible that imported meat and bone meal (MBM) into the USA reached domestic cattle and leads to an internal challenge in the early nineties.
A processing risk developed in the late 80s/early 90s when cattle imports from BSE risk countries were slaughtered or died and were processed (partly) into feed, together with some imports of MBM. This risk continued to exist, and grew significantly in the mid 90's when domestic cattle, infected by imported MBM, reached processing. Given the low stability of the system, the risk increased over the years with continued imports of cattle and MBM from BSE risk countries.
EFSA concludes that the current GBR level of USA is III, i.e. it is likely but not confirmed that domestic cattle are (clinically or pre-clinically) infected with the BSE-agent. As long as there are no significant changes in rendering or feeding, the stability remains extremely/very unstable. Thus, the probability of cattle to be (pre-clinically or clinically) infected with the BSE-agent persistently increases.
http://www.efsa.europa.eu/en/science/tse_assessments/gbr_assessments/573.html
http://www.efsa.europa.eu/etc/medialib/efsa/science/tse_assessments/gbr_assessments/573.Par.0004.File.dat/sr03_biohaz02_usa_report_v2_en1.pdf
Wednesday, July 16, 2008
Implementation of 2008 Feed Ban Enhancements Questions and Answers July 15, 2008
http://madcowfeed.blogspot.com/2008/07/implementation-of-2008-feed-ban.html
Thursday, July 10, 2008
A Novel Human Disease with Abnormal Prion Protein Sensitive to Protease update July 10, 2008
http://cjdmadcowbaseoct2007.blogspot.com/2008/07/novel-human-disease-with-abnormal-prion.html
Thursday, July 10, 2008 A New Prionopathy update July 10, 2008
http://cjdmadcowbaseoct2007.blogspot.com/2008/07/new-prionopathy-update-july-10-2008.html
SEAC Draft minutes of the 100th meeting held on 25th April 2008
http://seac992007.blogspot.com/2008/07/seac-draft-minutes-of-100th-meeting.html
HUMAN and ANIMAL TSE Classifications i.e. mad cow disease and the UKBSEnvCJD only theory JUNE 2008
http://cjdmadcowbaseoct2007.blogspot.com/2008/06/human-and-animal-tse-classifications-ie.html
Wednesday, July 16, 2008 Prevalence of the prion protein gene E211K variant in U.S. cattle Research Project:
Haplotype Structure of the Bovine Prion Gene Complex and Association with Bovine Spongiform Encephalopathy (Bse) Location: Animal Health Systems Research
Title: Prevalence of the prion gene E211K variant in U.S. cattle
http://bse-atypical.blogspot.com/2008/07/prevalence-of-prion-protein-gene-e211k.html
PEACE
Terry S. Singeltary Sr. P.O. Box 42 Bacliff, Texas USA 77518
Adopted date: 05/06/2008 Summary (0.1Mb)
Opinion (0.2Mb)
Summary
Following a request from the European Commission, the Panel on Biological Hazards (BIOHAZ) was asked to deliver a scientific Opinion on a TSE risk assessment from carcasses of ovine and caprine animals below 6 months of age from TSE infected flocks intended for human consumption. Its terms of reference were as follows: to provide an assessment on the existence of a significant additional risk to human health compared with the actual situation, founded on the scientific evidences, from the consumption of carcasses from ovine or caprine animals below 6 months of age from TSE affected flocks (without been subjected to a TSE rapid test and irrespectively of the genotype) provided that the entire head and the viscera of the thoracic and abdominal cavities are removed and excluded from human consumption and provided that BSE is excluded (in the outbreak) according to the procedure laid down in 3.2 (c), Chapter C of Annex X to the Regulation (EC) 999/2001. After clarification from the Commission, the BIOHAZ Panel was able to refine the ToR to focus on the change of human exposure that might result from the proposed change of risk management procedure and that it specifically required an estimate of the relative levels of TSE infectivity in the carcass of a lamb or kid less than 3 months of age from which spleen and ileum have been removed, compared to the carcass of a lamb or kid less than 6 months of age from which the spleen, the ileum, the head and the viscera of the abdominal and thoracic cavity have been removed. In answer to these ToR, the BIOHAZ Panel concluded: A quantitative comparison of infectivity load in both scenarios is not possible, because there are no data available on the amount of infectious tissues that would be still present on the carcasses of 3 months and 6 months of age of lambs and kids, prepared according to the terms of reference (i.e. 3 months with head and viscera from the thoracic and abdominal cavity remaining for human consumption, but excluding the spleen and the ileum which is currently removed as Specified Risk Material; 6 months of age without head and all the viscera from the thoracic and abdominal cavities). There is an increase, between 3 and 6 months of age, of the number of PrPres accumulating lymphoid formations. A part of these newly involved lymphoid formations would remain on dressed carcasses. In the worst case scenario, there would be an increase in infectivity level in lymphoid tissue between ages of 3 and 6 months (approximately 10 fold) on a per unit weight basis. The level of infectivity in secondary lymphoid tissues that may remain on the dressed carcasses, can reach by 6 months of age a level of infectivity per gram equivalent to 1/50 of that found in the same amount of brain tissue from a terminally affected sheep. Removal of the head and the thoracic and abdominal viscera will result in incomplete removal of the infectivity load at both 3 and 6 months of age. In the absence of new quantitative data on the tissue infectivity load in kids and lambs, the risk assessment and procedures for safe sourcing of small ruminant materials proposed in 2002 by the SSC, including the use of the combination of genotype and age as sourcing criteria, remain valid. The BIOHAZ Panel further recommends that to facilitate future attempts at quantitative risk assessments in this field, more experimental work is needed to define the variability and uncertainty of both the estimates of relative infectivity titre at different ages in young lambs and kids and of the weights of lymphoid tissue entering the food chain.
Publication date: 15/07/2008
http://www.efsa.europa.eu/EFSA/efsa_locale-1178620753812_1178720552868.htm
TSE risk assessment from carcasses of ovine and caprine animals below 6 months of age from TSE infected flocks intended for human consumption Scientific Opinion of the Panel on Biological Hazards (Question No EFSA-Q-2007-202) Adopted on 5 June 2008 SUMMARY Following a request from the European Commission, the Panel on Biological Hazards (BIOHAZ) was asked to deliver a scientific Opinion on a TSE risk assessment from carcasses of ovine and caprine animals below 6 months of age from TSE infected flocks intended for human consumption. Its terms of reference were as follows: to provide an assessment on the existence of a significant additional risk to human health compared with the actual situation, founded on the scientific evidences, from the consumption of carcasses from ovine or caprine animals below 6 months of age from TSE affected flocks (without been subjected to a TSE rapid test and irrespectively of the genotype) provided that the entire head and the viscera of the thoracic and abdominal cavities are removed and excluded from human consumption and provided that BSE is excluded (in the outbreak) according to the procedure laid down in 3.2 (c), Chapter C of Annex X to the Regulation (EC) 999/2001. After clarification from the Commission, the BIOHAZ Panel was able to refine the ToR to focus on the change of human exposure that might result from the proposed change of risk management procedure and that it specifically required an estimate of the relative levels of TSE infectivity in the carcass of a lamb or kid less than 3 months of age from which spleen and ileum have been removed, compared to the carcass of a lamb or kid less than 6 months of age from which the spleen, the ileum, the head and the viscera of the abdominal and thoracic cavity have been removed. In answer to these ToR, the BIOHAZ Panel concluded: • A quantitative comparison of infectivity load in both scenarios is not possible, because there are no data available on the amount of infectious tissues that would be still present on the carcasses of 3 months and 6 months of age of lambs and kids, prepared according to the terms of reference (i.e. 3 months with head and viscera from the thoracic and abdominal cavity remaining for human consumption, but excluding the spleen and the ileum which is currently removed as Specified Risk Material; 6 months of age without head and all the viscera from the thoracic and abdominal cavities). • There is an increase, between 3 and 6 months of age, of the number of PrPres accumulating lymphoid formations. A part of these newly involved lymphoid formations would remain on dressed carcasses. • In the worst case scenario, there would be an increase in infectivity level in lymphoid tissue between ages of 3 and 6 months (approximately 10 fold) on a per unit weight basis. Summary of opinion The EFSA Journal (2008) 719, 2-2 • The level of infectivity in secondary lymphoid tissues that may remain on the dressed carcasses, can reach by 6 months of age a level of infectivity per gram equivalent to 1/50 of that found in the same amount of brain tissue from a terminally affected sheep. • Removal of the head and the thoracic and abdominal viscera will result in incomplete removal of the infectivity load at both 3 and 6 months of age. • In the absence of new quantitative data on the tissue infectivity load in kids and lambs, the risk assessment and procedures for safe sourcing of small ruminant materials proposed in 2002 by the SSC, including the use of the combination of genotype and age as sourcing criteria, remain valid. The BIOHAZ Panel further recommends that to facilitate future attempts at quantitative risk assessments in this field, more experimental work is needed to define the variability and uncertainty of both the estimates of relative infectivity titre at different
http://www.efsa.europa.eu/EFSA/Scientific_Opinion/biohaz_op_ej719_tse_carcasses_smru_summary_en.pdf
TSE risk assessment from carcasses of ovine and caprine animals below 6 months of age from TSE infected flocks intended for human consumption 1 Scientific Opinion of the Panel on Biological Hazards (Question No EFSA-Q-2007-202) Adopted on 5 June 2008
snip...
CONCLUSIONS
1. General conclusions: • Lambs and kids from TSE affected flocks in the form of classical scrapie have a clearly higher probability of infection than those from the general population. In the general EU sheep population TSE prevalence at animal level is estimated to be about 0.1 %. In classical scrapie affected sheep flocks the reported prevalence vary from 3% to 41%. • In susceptible lambs (VRQ/VRQ), infectivity will replicate in lymphoid tissues from birth and involve most secondary lymphoid formations before 4 months old. • In worst cases, infectivity in lymphoid organs reaches its maximal level before 6 months old. This maximal level infectivity in lymphoid organs (per mass unit) can be estimated to be about 1/50 of the infectivity found in obex from a terminally affected ewe. • According to currently available data, carcasses of animals of less than two months of age, providing that the head and the thoracic and abdominal viscera are removed, do not contain detectable PrPres but this does not exclude the possibility of infectivity.
snip...
APPENDIX II. FURTHER DATA RELEVANT TO THE TIMING AND SPREAD OF INFECTION IN VRQ/VRQ LAMBS
a. Colostrum/Milk as a potential source of infectivity. Qualitative TSE risk assessments of the safety of milk from sheep and goats have been made in the past, but little published data have been available. Konold and colleagues have recently published a study of the transmission of scrapie from scrapie-affected dams to lambs by feeding from birth milk (and colostrum) taken during the later stages of scrapie-infection in the dams (Konold et al., 2008). Evidence of infection was detected as early as 44-46 days in the distal ileum of two lambs by immunohistochemistry for abnormal PrP (PrPres) and widespread infection inferred by RAMALT6 testing by 190-210 days of age. Both donor ewes and lambs were of the susceptible VRQ/VRQ genotype and the donor ewes were sourced from a flock with a ~ 10% prevalence of natural infection. This is directly relevant to the consideration of “a worst case scenario” and confirms previous work indicating lambs can become infected very soon after birth and that, within 6-7 months, the infection can be widely disseminated, at least in lymphoid tissue, in the susceptible animal.
b. The role of blood in spreading the agent within the body. One of the critical scientific uncertainties (for any naturally occurring TSE in any species) is that related to the possibility of infectivity in blood. Information on the incubation stage(s) wherein this happens is meagre and it is not yet known if this is an inconsistent chance event or an important way in which the pathogen spreads within the body. The data published by Houston et al. (2000) and Hunter et al. (2002) showed that a high volume blood transfusion from sheep to sheep can transmit BSE as well as scrapie within the same species. With both diseases, infectivity could also be transmitted using blood taken during the asymptomatic incubation period of the disease in the donor sheep. In the specific context of this mandate, Andreoletti and co-workers have reported infectivity in blood of pre-clinical VRQ/VRQ lambs at 3 months of age (Andreoletti et al., Neuroprion Edinburgh 2007).
c. Intestine: the anatomical location where infectivity is first detected. PrPres in the digestive tract has been described in sheep exposed to natural scrapie (van Keulen et al., 1999; Andreoletti et al., 2000). Most of the data available were obtained in natural scrapie and the prion protein genotype of the sheep is a critical factor in the uptake and dissemination of the agents of BSE and scrapie in the gut of the sheep. In VRQ/VRQ sheep exposed to natural scrapie infection, PrPres can be detected in ileal Peyer’s patches (PP) from 21 days post-partum and in other PP’s of the alimentary canal and in the tonsil of the lamb by 60 days of age. In similar conditions, PrPres is detectable in the enteric nervous system (ENS) at 7 months old, almost three months prior to its first detection in the obex (Andreoletti et al., 2000). Hence, during surveillance, screening the obex using rapid testing for PrPres is a poor indicator for the absence of TSE infection in the digestive tract of the lamb. 6 RAMALT stands for recto-anal mucosal associated lymphoid tissue.
snip... full text ;
http://www.efsa.europa.eu/EFSA/Scientific_Opinion/biohaz_op_ej719_tse_carcasses_smru_en.pdf
OPINION ON SAFE SOURCING OF SMALL RUMINANT MATERIALS (SAFE SOURCING OF SMALL RUMINANT MATERIALS SHOULD BSE IN SMALL RUMINANTS BECOME PROBABLE: GENOTYPE, BREEDING, RAPID TSE TESTING, FLOCKS CERTIFICATION AND SPECIFIED RISK MATERIALS) ADOPTED BY THE SCIENTIFIC STEERING COMMITTEE AT ITS MEETING OF 4-5 APRIL 2002
snip...
III.1.2. As for BSE in sheep, research data are available for only a few tens of animals: - Results to date indicate that the relation between sheep genotype and susceptibility to a TSE is similar for scrapie and BSE: the ARR genotypes are apparently resistant to development of clinical disease on challenge with BSE and animals carrying the glutamine (Q) allele at codon 171 are potentially susceptible to BSE and to scrapie. The influence of the genotype at codon 136 and 154 is not yet known for BSE but is being tested by direct challenge studies at IAH, UK. - New research data summarised in EC (2002) are consistent with the previously expressed view that BSE in sheep after oral exposure is pathogenetically closely similar to scrapie, particularly with respect to the tissue distribution of infectivity and/or PrPSc.
page 17 of 69...snip...end
http://ec.europa.eu/food/fs/sc/ssc/out257_en.pdf
ISSUE All Member States are required to produce a contingency plan in the event BSE were found in sheep.
The UK is currently finalising its detailed plan, for submission to the Commission this summer. The European Commission has recently produced guidelines for Member States on the points which should be considered in drawing up their contingency plans. (Annex 1). The guidelines suggest that Member States should consider a worst case scenario where sheep meat is excluded from the food chain. This is based on an opinion, adopted by the Scientific Steering Committee (SSC) in April 2002, entitled “Safe sourcing of small ruminant materials” (Annex 2). The SSC Opinion states that if BSE were found in sheep, then only the following animals should be allowed into the food chain: • ARR homozygous sheep under the age of 18 months • ARR heterozygous sheep under the age of 6 months. • Sheep (and goat) milk, colostrum and milk products from suspect BSE cases should be excluded from the food chain. The EC guidelines (SANCO/19/2003 Rev.2) state a worst case scenario where: • small ruminant meat is excluded from the food chain unless derived from: - homozygous ARR sheep under the age of 18 months - heterozygous sheep under the age of 6 months • sheep and goat milk is excluded from the food and feed chain: - completely, or - unless derived from sheep carrying at least one ARR allele, or - unless derived from holdings certified TSE resistant or TSE free on the basis of solid criteria. They should also make an inventory of their capacity in terms of genotyping, individual identification and registration of animals, TSE testing and in terms of flock certification on the basis of history, monitoring etc.
CONFIDENTIAL PAPER No: SEAC 78/9 Amendment 2 2 In March 2002, a SEAC Sub-Group considered the risks associated with certain genotypes entering the food chain if BSE were ever isolated from sheep. In contrast to the SSC opinion, SEAC concluded that: • In line with previous SEAC advice, only animals carrying the ARR allele should enter the food chain • On a precautionary basis, the 12 month cut off previously advised by SEAC remained appropriate for ARR heterozygotes. However, in view of existing SRM regulations there was no justification for any age cut off in ARR homozygotes • In line with SEAC advice in 2001, only milk from ARR homozygous sheep could be considered as highly unlikely to contain the infectious agent. Further experimental work was required before potential risks from small ruminant milk from goats and semi-resistant or susceptible sheep could be excluded. There is therefore a disparity of opinion between the SSC and SEAC on this issue. Whilst recognising the uncertainties relating to the science in this area, it is important that contingency planning is based on the most up to date scientific developments and assessments of risk that are available. SEAC will be presented with an update on the ongoing BSE in sheep studies, funded by Defra (Annex 31). This covering paper also provides a history of previous SEAC advice on this issue. BACKGROUND...snip...end
http://www.seac.gov.uk/papers/78-9-closed.pdf
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 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 is 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 emphasized by the finding that some strains of scrapie produce lesions identical to the once which characterize the human dementias"
Whether true or not. the hypothesis that these agents might be transmissible to man raises two considerations. First, the safety of laboratory personnel requires prompt attention. Second, action such as the "scorched meat" policy of USDA makes the solution of the scrapie problem urgent if the sheep industry is not to suffer grievously.
snip...
76/10.12/4.6
http://www.bseinquiry.gov.uk/files/yb/1976/10/12004001.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.
PMID: 6997404
http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=6997404&ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstractPlus
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://www.bseinquiry.gov.uk/files/yb/1994/02/07002001.pdf
Like lambs to the slaughter
31 March 2001 Debora MacKenzie Magazine issue 2284
What if you can catch old-fashioned CJD by eating meat from a sheep infectedwith scrapie?FOUR years ago, Terry Singeltary watched his mother die horribly from adegenerative brain disease. Doctors told him it was Alzheimer's, butSingeltary was suspicious. The diagnosis didn't fit her violent symptoms,and he demanded an autopsy. It showed she had died of sporadicCreutzfeldt-Jakob disease.
Most doctors believe that sCJD is caused by a prion protein deforming bychance into a killer. But Singeltary thinks otherwise. He is one of a numberof campaigners who say that some sCJD, like the variant CJD related to BSE,is caused by eating meat from infected animals. Their suspicions havefocused on sheep carrying scrapie, a BSE-like disease that is widespread inflocks across Europe and North America.
Now scientists in France have stumbled across new evidence that adds weightto the campaigners' fears. To their complete surprise, the researchers foundthat one strain of scrapie causes the same brain damage in ...
The complete article is 889 words long.
full text;
http://www.newscientist.com/article/mg16922840.300-like-lambs-to-the-slaughter.html
Neurobiology Adaptation of the bovine spongiform encephalopathy agent to primates and comparison with Creutzfeldt-Jakob disease: Implications for human health
Corinne Ida Lasmézas*,, Jean-Guy Fournier*, Virginie Nouvel*, Hermann Boe*,Domíníque Marcé*, François Lamoury*, Nicolas Kopp, Jean-Jacques Hauw§, JamesIronside¶, Moira Bruce, Dominique Dormont*, and Jean-Philippe Deslys** Commissariat à l'Energie Atomique, Service de Neurovirologie, Directiondes Sciences du Vivant/Département de Recherche Medicale, Centre deRecherches du Service de Santé des Armées 60-68, Avenue du Général Leclerc,BP 6, 92 265 Fontenay-aux-Roses Cedex, France; Hôpital Neurologique PierreWertheimer, 59, Boulevard Pinel, 69003 Lyon, France; § Laboratoire deNeuropathologie, Hôpital de la Salpêtrière, 83, Boulevard de l'Hôpital,75013 Paris, France; ¶ Creutzfeldt-Jakob Disease Surveillance Unit, WesternGeneral Hospital, Crewe Road, Edinburgh EH4 2XU, United Kingdom; andInstitute for Animal Health, Neuropathogenesis Unit, West Mains Road,Edinburgh EH9 3JF, United Kingdom
Edited by D. Carleton Gajdusek, Centre National de la RechercheScientifique, Gif-sur-Yvette, France, and approved December 7, 2000(received for review October 16, 2000)
Abstract
There is substantial scientific evidence to support the notion that bovinespongiform encephalopathy (BSE) has contaminated human beings, causingvariant Creutzfeldt-Jakob disease (vCJD). This disease has raised concernsabout the possibility of an iatrogenic secondary transmission to humans,because the biological properties of the primate-adapted BSE agent areunknown. We show that (i) BSE can be transmitted from primate to primate byintravenous route in 25 months, and (ii) an iatrogenic transmission of vCJDto humans could be readily recognized pathologically, whether it occurs bythe central or peripheral route. Strain typing in mice demonstrates that theBSE agent adapts to macaques in the same way as it does to humans andconfirms that the BSE agent is responsible for vCJD not only in the UnitedKingdom but also in France. The agent responsible for French iatrogenicgrowth hormone-linked CJD taken as a control is very different from vCJD butis similar to that found in one case of sporadic CJD and one sheep scrapieisolate. These data will be key in identifying the origin of human cases ofprion disease, including accidental vCJD transmission, and could providebases for vCJD risk assessment.
http://www.pnas.org/cgi/content/full/041490898v1
full text ;
http://scrapie-usa.blogspot.com/2006/12/scrapie-usa.html
Saturday, December 08, 2007 SCRAPIE HB Parry Seriously’ (YB88/6.8/4.1)
HB Parry Seriously’ (YB88/6.8/4.1)
IF the scrapie agent is generated from ovine DNA and thence causes disease in other species, then perhaps, bearing in mind the possible role of scrapie in CJD of humans (Davinpour et al, 1985), scrapie and not BSE should be the notifiable disease.
http://www.bseinquiry.gov.uk/files/yb/1988/06/08004001.pdf
1: Neuroepidemiology. 1985;4(4):240-9.
Sheep consumption: a possible source of spongiform encephalopathy in humans.
Davanipour Z, Alter M, Sobel E, Callahan M.
A fatal spongiform encephalopathy of sheep and goats (scrapie) shares many characteristics with Creutzfeldt-Jakob disease (CJD), a similar dementing illness of humans. To investigate the possibility that CJD is acquired by ingestion of contaminated sheep products, we collected information on production, slaughtering practices, and marketing of sheep in Pennsylvania. The study revealed that sheep were usually marketed before central nervous system signs of scrapie are expected to appear; breeds known to be susceptible to the disease were the most common breeds raised in the area; sheep were imported from other states including those with a high frequency of scrapie; use of veterinary services on the sheep farms investigated and, hence, opportunities to detect the disease were limited; sheep producers in the area knew little about scrapie despite the fact that the disease has been reported in the area, and animal organs including sheep organs were sometimes included in processed food. Therefore, it was concluded that in Pennsylvania there are some 'weak links' through which scrapie-infected animals could contaminate human food, and that consumption of these foods could perhaps account for spongiform encephalopathy in humans. The weak links observed are probably not unique to Pennsylvania.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3915057&dopt=Abstract
snip...
Scrapie has been transmitted in our laboratory to five species of monkeys (Tables 9 and 10) (23, 31, 32), and such transmission has occurred using infected brain from naturally infected sheep and from experimentally infected goats and mice (Figures 22a, b, c). The disease produced is clinically and pathologically indistinguishable from experimental CJD in these species. .........
SNIP...
22b. Primary transmission of goat-adapted scrapie (Compton, England strain) to the squirrel monkey and to mice and the transmission of mouse-adapted scrapie to two species of Old World and three species of New World monkeys. Numbers in parentheses are the number of months elapsed since inoculation, during which the animal remained asymptomatic.
SNIP...
22c. Transmission of mouse-adapted sheep scrapie (U. S. strain 434-3-897) to a squirrel monkey 38 months following intracerebral inoculation with a suspension of scrapie-infected mouse brain containing 10a7.3 infectious units of virus per ml. This animal showed signs of ataxia, tremors and incoordination, and the disease was confirmed histologically. See (b) for an explanation of symbols.
SNIP...
Figure 23. Transmissible mink encephalopathy (TME), a rare disease of American ranch mink, is possibly a form of scrapie. The clinical picture and histopathological lesions attendant in the brain, resemble that of scrapie, and scrapie sheep carcasses were fed to mink on ranches on which TME appeared. The disease is transmissible to sheep, goats, certain rodents and New and Old World monkeys. Illustrative data on the primary transmissions of transmissible mink encephalopathy to one species of New World monkey and two species of Old World monkeys, and serial passage of the virus in squirrel, rhesus and stumptailed monkeys are presented in this Figure. Incubation periods are shown in months that elapsed between inoculation and onset of clinical disease. (Figure includes information from our laboratory and from R. F. Marsh, R. J. Eckroade, and R. P. Hanson.)
SNIP... end
SOURCE;
UNCONVENTIONAL VIRUSES AND THE ORIGIN
AND DISAPPEARANCE OF KURU
Nobel Lecture, December 13, 1976
by D. CARLETON GAJDUSEK
National Institutes of Health, Bethesda, Maryland, U.S.A.
snip... see ;
http://scrapie-usa.blogspot.com/2007/12/scrapie-hb-parry-seriously-yb886841.html
Monday, December 24, 2007 Pathogenesis of bovine spongiform encephalopathy in sheep
http://scrapie-usa.blogspot.com/2007/12/pathogenesis-of-bovine-spongiform.html
Friday, February 15, 2008 SCRAPIE and TSE to human UPDATE 2008 (ambiguous terms of transition and reality set in)
snip...
2. In relation to conclusion 2 in page 7 the Authority is invited to specify the scientific evidences which do not allow to exclude transmissibility to humans of “other TSE agents” other than BSE. Conclusion 2 in page 7 of the EFSA 2007 opinion states that: “The BSE agent is the only TSE agent identified as zoonotic. However, in view of their diversity it is currently not possible to exclude transmissibility to humans of other animal TSE agents.”
In the EFSA 2007 opinion under 3.2.3. the Panel states that:
• “There are significant uncertainties associated with the question whether TSE agents in their whole spectrum may cross the human transmission barrier under natural conditions”.
This statement is supported both by scientific evidence and considerations, referenced in the EFSA 2007 opinion:
• Scientific evidence from transmission studies to primates: - Transmission of Classical Scrapie from a TSE agent adapted in hamster was demonstrated by oral challenge in squirrel monkey (Saimiri sciureus) (Gibbs et al., 1980);
- Transmission of Classical Scrapie from two distinct sheep sources by intracerebral challenge in cynomologus monkey (Macaca fascicularis) and marmoset monkey (Callithrix jacchus) (Gibbs and Gajdusek, 1972; Baker et al., 1988).
• Scientific considerations on TSE epidemiology: - “The assumed lack of association between TSEs in humans and those in small ruminants […] may be biased by a number of factors: (i) The lack of a data on the historical real prevalence and distribution of small ruminant TSEs, at a time where only passive surveillance was performed; (ii) the lack of understanding of the true biodiversity of TSEs in small ruminants in terms of both Classical and Atypical agents; (iii) the lack of understanding of the diversity of TSEs in humans due to the limited molecular and bioassay characterisation of human TSEs also in relation to the number and spectrum of neurodegenerative diseases of humans; (iv) the predicted phenotype of disease that might arise should an animal derived TSE transmit to humans.” The EFSA Journal (2008) 626, 5-11
Further evidence is provided by:
• In vitro conversion assays: Raymond et al. (1997) studied whether there is a correlation between in vitro conversion efficiencies and known transmissibility of BSE, sheep Scrapie and CJD, and found limited conversion of human PrP-sen to PrP-res driven by PrP-res associated with both Scrapie (PrPSc) and BSE (PrPBSE). They concluded that “the inherent ability of these infectious agents of BSE and Scrapie to affect humans following equivalent exposure may be finite but similarly low”. Nevertheless, uncertainty arises from the fact that this is a simple in vitro model of a complex in vivo situation.
• Laboratory transmission studies with animal models: Since the publication of the Opinion new data have become available with regards to L type of BSE, which has now been identified in various EU members states (Biacabe et al., 2004; Casalone et al., 2004; Baron et al., 2007). This TSE agent, differing from that causing Classical BSE by its biochemical signature and transmission features in mouse models, has been transmitted to a Tg mouse model expressing Human M129 PRP gene (Beringue et al. 2007)2. Here again, uncertainty arises from the limitations of these animal models for the estimation of the human species barrier. These ‘proof of principle’ experiments provide data supporting the ability of TSE agents other than those causing Classical BSE to cross the human species barrier.
Even so, it is important to remember that as mentioned in the EFSA 2007 opinion, transmission to primates:
• “… does not allow to take into account the human gene PRNP polymorphisms (in particular the M/V 129), that have been identified to play a major role on relative susceptibility towards prion disease. In addition, genes other than the PrP gene may also be influential in determining overall susceptibility to TSEs.” Despite the interests in the area, studies of the transmissibility of currently known TSE agents using animal models will remain incomplete for several years.
In conclusion, the reply to the ToR number 2 is:
• Experimental transmissions to primate and to transgenic (Tg) mouse models expressing the human PrP gene, are currently used as to evaluate the potential capacity of a TSE agent to cross the human species barrier.
• TSE agents other than the Classical BSE agent from three field TSE cases (two Classical Scrapie cases and one L type BSE case) have been demonstrated to cross the modelled human species barrier.
• Some limitations to these models have to be considered, which include:
(i) The uncertainty of how well they represent the human species barrier. (ii) The uncertainty of how well the experimental inoculation route employed represents exposure under natural conditions. 2 Transmission of this TSE agent by intracerebral challenge to primates (Macaques) has been reported by Comoy et al. at the 2006 Prion Congress held in Torino. A scientific paper reporting this finding has been submitted for peer review publication. The EFSA Journal (2008) 626, 6-11
snip...
http://ec.europa.eu/dgs/health_consumer/library/pub/pub07_en.pdf
EFSA 2005. Opinion of the Scientific Panel on Biological Hazards on the request from the European Commission on classification of Atypical Transmissible Spongiform Encephalopathy (TSE) cases in small ruminants. The EFSA Journal 276: 1-30.
http://www.efsa.europa.eu/EFSA/efsa_locale-1178620753812_1178620776235.htm
The EFSA Journal (2008) 626, 11-11
EFSA 2007. Opinion of the Scientific Panel on Biological Hazards on a request from the European Commission on certain aspects related to the risk of Transmissible Spongiform Encephalopathies (TSEs) in ovine and caprine animals. The EFSA Journal 466: 1-10.
http://www.efsa.europa.eu/EFSA/efsa_locale-1178620753812_1178620775196.htm
Date: September 26, 2007 at 4:06 pm PST
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.
http://www.prion2007.com/pdf/Prion%20Book%20of%20Abstracts.pdf
snip... see;
http://scrapie-usa.blogspot.com/2008/02/scrapie-and-tse-to-human-update-2008.html
Saturday, April 12, 2008 Evidence of scrapie transmission via milk
http://scrapie-usa.blogspot.com/2008/04/evidence-of-scrapie-transmission-via.html
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.
Edited by Stanley B. Prusiner, University of California, San Francisco, CA, and approved September 12, 2005 (received for review March 21, 2005)
http://www.pnas.org/cgi/content/abstract/0502296102v1
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
In FY 2007, 331 scrapie cases have been confirmed and reported by the National Veterinary Services Laboratories (NVSL), including 59* Regulatory Scrapie Slaughter Surveillance (RSSS) cases (Figure 5 and Slide 16). In FY 2007, two field cases, one validation case, and two RSSS cases were consistent with Nor-98 scrapie. The Nor98-like cases originated from flocks in California, Minnesota, Colorado, Wyoming and Indiana respectively. Nineteen cases of scrapie in goats have been reported since 1990 (Figure 6). The last goat case was reported in September 2007.
snip...
see full report here ;
http://www.aphis.usda.gov/animal_health/animal_diseases/scrapie/downloads/yearly_report.pps
http://nor-98.blogspot.com/2008/06/scrapie-usa-update-june-2008-nor-98.html
http://nor-98.blogspot.com/
now, confusious is confused again. why do some countries have their TSE reported on the OIE weekly listing of disease on the OIE website, but others like the USA, do not $$$
case in point ;
SCRAPIE PORTUGAL
Information received on 16/07/2008 from Mr Carlos Agrela Pinheiro, Chief Veterinary Officer, Director General, Direcçao-Geral de Veterinária, Ministério da Agricultura, LISBONNE, Portugal
http://www.oie.int/wahid-prod/public.php?page=single_report&pop=1&reportid=7201
Wednesday, June 11, 2008
OIE Recognition of the BSE Status of Members RESOLUTION No. XXI (Adopted by the International Committee of the OIE on 27 May 2008)
snip...
CONSIDERING THAT
1. Adoption of subsequent Resolutions* since the 67th General Session of the OIE International Committee has established a procedure for annually updating a list of Members, categorised by their BSE risk according to the provisions of theTerrestrial Code,
2. During the 70th General Session, the International Committee adopted Resolution No. XVIII asking Members applying for a BSE risk evaluation to meet part of the costs sustained by the OIE Central Bureau in the evaluation process,
3. During the 72nd General Session, the OIE adopted Resolution No. XXI requesting the Director General to inform Delegates of Members whose country or zones are recognised with regard to their BSE risk status should annually confirm during the month of November whether their risk status and the criteria by which their status was recognised have remained unchanged,
4. Information published by the OIE is derived from declarations made by the official Veterinary Services of Members. The OIE is not responsible for inaccurate publication of a Member disease status based on inaccurate information, changes in epidemiological status or other significant events that were not promptly reported to the Central Bureau, subsequent to the time of declaration of the BSE risk status.
THE COMMITTEE
RESOLVES THAT
1. The Director General publish the following list of Members recognised as having a negligible BSE risk in accordance with Chapter 2.3.13. of the Terrestrial Code:
Australia, Argentina, Finland, Iceland, New Zealand, Norway, Paraguay, Singapore, Sweden and Uruguay.
2. The Director General publish the following list of Members recognised as having a controlled BSE risk in accordance with Chapter 2.3.13. of the Terrestrial Code:
Austria Belgium Brazil Canada Chile Chinese Taipei Cyprus Czech Republic Denmark Estonia France Germany Greece Hungary Ireland Italy Latvia Lichtenstein Lithuania Luxembourg Malta Mexico Netherlands Poland Portugal Slovak Republic Slovenia Spain Switzerland United Kingdom United States of America
AND
3. The Delegates of these Members will immediately notify the Central Bureau if BSE occurs in their countries or their territories.
_________
(Adopted by the International Committee of the OIE on 27 May 2008)
* 67th General Session (GS) Resolution No (Res) XVI and Res XI; 69th GS Res XV, and 71st GS Res XXII, 72nd GS Res XXIV and Res XXI..
http://www.oie.int/eng/info/en_statesb.htm?e1d6
IN A NUT SHELL ;
(Adopted by the International Committee of the OIE on 23 May 2006)
11. Information published by the OIE is derived from appropriate declarations made by the official Veterinary Services of Member Countries. The OIE is not responsible for inaccurate publication of country disease status based on inaccurate information or changes in epidemiological status or other significant events that were not promptly reported to the Central Bureau,
http://www.oie.int/eng/Session2007/RF2006.pdf
snip...SEE FULL TEXT with facts and sources @ ;
http://usdavskorea.blogspot.com/2008/06/oie-recognition-of-bse-status-of.html
http://organicconsumers.org/forum/index.php?showtopic=1566
BSE BASE MAD COW TESTING TEXAS, USA, AND CANADA
http://madcowtesting.blogspot.com/
Attachment to Singeltary comment
January 28, 2007
Greetings APHIS,
I would kindly like to submit the following to ;
BSE; MRR; IMPORTATION OF LIVE BOVINES AND PRODUCTS DERIVED FROM BOVINES [Docket No. APHIS-2006-0041] RIN 0579-AC01
[Federal Register: January 9, 2007 (Volume 72, Number 5)] [Proposed Rules] [Page 1101-1129] From the Federal Register Online via GPO Access [wais.access.gpo.gov] [DOCID:fr09ja07-21]
http://www.regulations.gov/fdmspublic/component/main?main=DocumentDetail&o=09000064801f8152
BSE; MRR; IMPORTATION OF LIVE BOVINES AND PRODUCTS DERIVED FROM BOVINES [Docket No. APHIS-2006-0041] RIN 0579-AC01 Date: January 9, 2007 at 9:08 am PST
http://www.regulations.gov/fdmspublic/component/main?main=DocumentDetail&o=09000064801f3412
bottom line, you don't look, you dont find, you don't report, you dont have, thus, you have this imaginary classification called the BSE MRR 'CONTROLLED RISK' ;-)
THE REALITY IS ;
EFSA Scientific Report on the Assessment of the Geographical BSE-Risk (GBR) of the United States of America (USA)
Summary of the Scientific Report
The European Food Safety Authority and its Scientific Expert Working Group on the Assessment of the Geographical Bovine Spongiform Encephalopathy (BSE) Risk (GBR) were asked by the European Commission (EC) to provide an up-to-date scientific report on the GBR in the United States of America, i.e. the likelihood of the presence of one or more cattle being infected with BSE, pre-clinically as well as clinically, in USA. This scientific report addresses the GBR of USA as assessed in 2004 based on data covering the period 1980-2003.
The BSE agent was probably imported into USA and could have reached domestic cattle in the middle of the eighties. These cattle imported in the mid eighties could have been rendered in the late eighties and therefore led to an internal challenge in the early nineties. It is possible that imported meat and bone meal (MBM) into the USA reached domestic cattle and leads to an internal challenge in the early nineties.
A processing risk developed in the late 80s/early 90s when cattle imports from BSE risk countries were slaughtered or died and were processed (partly) into feed, together with some imports of MBM. This risk continued to exist, and grew significantly in the mid 90's when domestic cattle, infected by imported MBM, reached processing. Given the low stability of the system, the risk increased over the years with continued imports of cattle and MBM from BSE risk countries.
EFSA concludes that the current GBR level of USA is III, i.e. it is likely but not confirmed that domestic cattle are (clinically or pre-clinically) infected with the BSE-agent. As long as there are no significant changes in rendering or feeding, the stability remains extremely/very unstable. Thus, the probability of cattle to be (pre-clinically or clinically) infected with the BSE-agent persistently increases.
http://www.efsa.europa.eu/en/science/tse_assessments/gbr_assessments/573.html
http://www.efsa.europa.eu/etc/medialib/efsa/science/tse_assessments/gbr_assessments/573.Par.0004.File.dat/sr03_biohaz02_usa_report_v2_en1.pdf
Wednesday, July 16, 2008
Implementation of 2008 Feed Ban Enhancements Questions and Answers July 15, 2008
http://madcowfeed.blogspot.com/2008/07/implementation-of-2008-feed-ban.html
Thursday, July 10, 2008
A Novel Human Disease with Abnormal Prion Protein Sensitive to Protease update July 10, 2008
http://cjdmadcowbaseoct2007.blogspot.com/2008/07/novel-human-disease-with-abnormal-prion.html
Thursday, July 10, 2008 A New Prionopathy update July 10, 2008
http://cjdmadcowbaseoct2007.blogspot.com/2008/07/new-prionopathy-update-july-10-2008.html
SEAC Draft minutes of the 100th meeting held on 25th April 2008
http://seac992007.blogspot.com/2008/07/seac-draft-minutes-of-100th-meeting.html
HUMAN and ANIMAL TSE Classifications i.e. mad cow disease and the UKBSEnvCJD only theory JUNE 2008
http://cjdmadcowbaseoct2007.blogspot.com/2008/06/human-and-animal-tse-classifications-ie.html
Wednesday, July 16, 2008 Prevalence of the prion protein gene E211K variant in U.S. cattle Research Project:
Haplotype Structure of the Bovine Prion Gene Complex and Association with Bovine Spongiform Encephalopathy (Bse) Location: Animal Health Systems Research
Title: Prevalence of the prion gene E211K variant in U.S. cattle
http://bse-atypical.blogspot.com/2008/07/prevalence-of-prion-protein-gene-e211k.html
PEACE
Terry S. Singeltary Sr. P.O. Box 42 Bacliff, Texas USA 77518
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