Wednesday, March 3, 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.


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.

see full text ;

Monday, December 14, 2009

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

Epidemiology of Scrapie in the United States 1977

Tuesday, April 28, 2009

Nor98-like Scrapie in the United States of America


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.



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 (; 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.


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.

Monday, December 1, 2008 When Atypical Scrapie cross species barriers


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.


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.

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

Tuesday, June 3, 2008


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.



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)


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).

Thursday, January 07, 2010

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


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. ........


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



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


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.



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

Monday, March 1, 2010


Tuesday, March 2, 2010

Animal Proteins Prohibited in Ruminant Feed/Adulterated/Misbranded Rangen Inc 2/11/10 USA

. 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.

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Over the next 8-10 weeks, approximately 40% of all the adult mink on the farm died from TME.


The rancher was a ''dead stock'' feeder using mostly (>95%) downer or dead dairy cattle...

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 ;

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


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.

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)


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.

Monday, November 23, 2009



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 ???


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.


Monday, May 19, 2008


Sunday, August 10, 2008

A New Prionopathy OR more of the same old BSe and sporadic CJD

full text ;

Saturday, February 27, 2010

SEAC Agenda 104th meeting on Friday 5th March 2010

Saturday, February 27, 2010


Prions: Protein Aggregation and Infectious Diseases


Institute of Neuropathology, University Hospital of Zurich, Zurich, Switzerland


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.


Physiol Rev • VOL 89 • OCTOBER 2009 •

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*


BSE caused by spontaneous misfolding of the prion protein has not been proven.


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.



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.

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

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