BSE ATYPICAL USA

Comparative analysis of Japanese and foreign L-type BSE prions

2012-01-05T11:50:00.000-08:00

Short Communication

Comparative analysis of Japanese and foreign L-type BSE prions

Volume 6, Issue 1 January/February/March 2012

Kentaro Masujin, Ritsuko Miwa, Hiroyuki Okada, Shirou Mohri and Takashi Yokoyama View affiliations

L-type bovine spongiform encephalopathy (BSE) is an atypical form of BSE. To characterize the Japanese L-type BSE prion, we conducted a comparative study of the Japanese and foreign L-type BSE isolates. The L-type BSE isolates of Japan, Germany, France and Canada were intracerebrally inoculated into bovinized prion protein-overexpressing transgenic mice (TgBoPrP). All the examined L-type BSE isolates were transmitted to TgBoPrP mice, and no clear differences were observed in their biological and biochemical properties. Here, we present evidence that the Japanese and Canadian L-type BSE prions are identical to those from the European cases.

http://www.landesbioscience.com/journals/prion/article/18429/

Tuesday, December 15, 2009

Intraspecies transmission of L-type-like bovine spongiform encephalopathy detected in Japan

NOTE

http://bse-atypical.blogspot.com/2009/12/intraspecies-transmission-of-l-type.html

Importation of Whole Cuts of Boneless Beef from Japan [Docket No. 05-004-1] RIN 0579-AB93 TSS SUBMISSION

Date: August 24, 2005 at 2:47 pm PST August 24, 2005

http://docket-aphis-2006-0041.blogspot.com/2012/01/importation-of-whole-cuts-of-boneless.html

Wednesday, August 20, 2008

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

SNIP...

IN CONFIDENCE

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

http://www.bseinquiry.gov.uk/files/yb/1992/10/26002001.pdf

SEE ;

http://web.archive.org/web/20040315054541/http://www.bseinquiry.gov.uk/files/yb/1992/10/26002001.pdf

COLLINGE THREATENS TO GO TO MEDIA

http://www.bseinquiry.gov.uk/files/yb/1992/12/16005001.pdf

SEE ;

http://web.archive.org/web/20040315075058/http://www.bseinquiry.gov.uk/files/yb/1992/12/16005001.pdf

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

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

snip...

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

R Bradley

http://www.bseinquiry.gov.uk/files/yb/1993/02/17001001.pdf

SEE ;

http://web.archive.org/web/20041226015613/http://www.bseinquiry.gov.uk/files/yb/1993/02/17001001.pdf

IN CONFIDENCE

BSE ATYPICAL LESION DISTRIBUTION

http://www.bseinquiry.gov.uk/files/yb/1993/03/14001001.pdf

SEE ;

http://web.archive.org/web/20041226015813/http://www.bseinquiry.gov.uk/files/yb/1993/03/14001001.pdf

1983

BSE CONSULTANT

APPROVAL OF MATERIAL FOR PUBLICATIONS

All material for publication including written works to be published in scientific journals, books, proceedings of scientific meetings, abstracts of verbally delivered papers and the like should be scrutinized for risk to the Ministry before dispatch to the publishers.............

full text;

http://www.bseinquiry.gov.uk/files/yb/1983/10/12001001.pdf

SEE ;

http://web.archive.org/web/20041031210056/http://www.bseinquiry.gov.uk/files/yb/1983/10/12001001.pdf

- 10 -

19. On 18th February, 1987 (YB87/2.18/1.1) I reported to Dr Watson and Dr Shreeve on a further case which we had received from Truro VIC. The brain had shown neuronal vacuolation and in brain extracts there were fibrils that were similar in size and appearance to SAFs from sheep with scrapie. The Virology Department was studying the brain further and considering a transmission study. A few weeks before this, I had discussed the possibility of a transmission study with Michael Dawson, a research officer in the Virology Department and an expert in viral diseases in sheep, and we were considering carefully the safety aspects. In my note I raised the question of whether we should disclose the information we had more widely to the VIS because this may assist in getting any other cases referred to CVL but there was the difficulty that we knew very little about the disorder and would be unable to deal with queries that might be raised.

20. On 23rd February, 1987 (YB87/2.23/1.1) I sent Mr Wells a note asking him to prepare a statement for publication in Vision, the in-house newsheet prepared by the VIS for the SVS, setting out details of what we had discovered. On 24th February, 1987 (YB87/2.25/2.1) Gerald Wells indicated in a note to me that he had discussed the proposed article with Mr Dawson and they both believed that it could be damaging to publish anything at that stage. They believed cases would be referred to CVL in any event because they were unusual and they did not feel "Vision" was an appropriate publication because its confidentiality was questionable and might lead to referrals to veterinary schools rather than CVL. Gerald Wells was also concerned about the resources available in his section to deal with referred cases. I replied (YB87/2.25/2.1) indicating a draft statement was needed by the Director before a decision on publication could be made. Gerald Wells prepared a draft statement (YB87/3.2/2.1) and sent it to me on 2nd March, 1987. In his cover note (YB87/3.2/1.1) he commented that he believed the distribution of any statement about the new disease outside of CVL to be premature because there was so little information available about the new disease. I passed on a copy of Gerald Wells' note to Dr Watson (YB87/3.2/3.1). I discussed the matter of publication with Dr Watson. No decision had been taken to publish any material at that stage and I sent a note to Gerald Wells letting him know the position and confirming that his views and those of Michael Dawson would be taken into account when a decision was taken.

- 11 -

21. In March, 1987 serious consideration was given to possible transmission (e.g. to hamsters) and other experiments (other than the collection of epidemiological data by the VIS and clinicopathology which had been in progress since the first cases were recognised in November, 1986).

22. On 23rd April, 1987 I sent a report (YB87/4.23/1.1) to Dr Watson and Dr Shreeve informing them that nine control brains were being examined for SAFs and a cow which appeared to be affected with BSE had been purchased for observation. The cow had come from the farm where the original cases had developed and had arrived at CVL on 22nd April, 1987.

23. On 15th May, 1987 Dr Watson informed me that the proposed "Vision" draft would be circulated to VICs in England and Wales if it was approved by management. On 22nd May, 1987 I was copied in on a note (YB87/5.22/2.1) from B.M Williams, (who I believe was Head of the VIS at this time but retired shortly after this), to Dr Watson. This confirmed that the draft prepared for publication in Vision was approved but that the final paragraph should be amended to make it clear that knowledge of the new disease should not be communicated to other research institutes or university departments. At a meeting with Dr Watson on 2nd June, 1987 he informed me that no communication should be made with NPU until after the meeting with the CVO on 5th June, 1987 (see my note of 3rd June, 1987 – YB87/6.3/1.1). We needed much more data and information to answer inevitable queries. ...

http://www.bseinquiry.gov.uk/files/ws/s071.pdf

SEE ;

http://web.archive.org/web/20071013202003/http://www.bseinquiry.gov.uk/files/ws/s071.pdf

http://www.publications.parliament.uk/pa/cm199900/cmselect/cmsctech/465/465m48.htm

*This case study accompanies the IRGC report “Risk Governance Deficits: An analysis and illustration of the most common deficits in risk governance”.

The Bovine Spongiform Encephalopathy (BSE) Epidemic in the United Kingdom

By Belinda Cleeland1

SNIP...

A6 Misrepresenting information about risk

From the very beginning of the BSE outbreak, not only was knowledge misrepresented by the British government, but in some cases it was even withheld. For example, after the initial diagnosis of BSE by the SVS in late 1986, there was an embargo placed on the sharing, or making public, of any BSE-related information that ran until mid-1987. Also, up until at least 1990, outside scientists that requested access to BSE data to conduct further studies were denied, despite the fact the improved scientific understanding of the disease had the greatest potential to minimise the impact of the epidemic. Even government scientists within the CVL have acknowledged that there was a culture of suppressing information, to the point that studies revealing damaging evidence (e.g. that there was a causal link between BSE and the new encephalopathy found in cats) were denied publication permission [Ashraf, 2000].

The withholding of such information allowed the government to publicly assert that BSE was just like another version of scrapie – not transmissible to humans – and that there was “clear scientific evidence that British beef is perfectly safe” [UK House of Commons, 1990].2 This was certainly a misrepresentation of the knowledge held at the time, and one that was only possible due to the suppression of some scientific findings and recommendations. Of course, the main reason for this misrepresentation of knowledge was the protection of agricultural and industrial interests – the specific stakeholder favoured in this case was the British beef industry, which stood to lose billions of pounds if a large number of its animals had to be slaughtered, if export bans were put in place, or if costly regulations were implemented.

To protect the interests of the beef industry, the government would assert on many occasions that British beef was safe to eat and that regulatory controls already implemented would prevent any 2 This comment was made by the Agriculture Minister to the House of Commons.

contaminated material from entering the food chain. This was also a misrepresentation of knowledge, as the government was fully aware that their measures were not designed to eliminate exposure, but only to diminish the risk [van Zwanenberg & Millstone, 2002:161].

What’s more, many uncertainties relating to the transmissibility of the disease were either down-played or ignored, resulting in an overstatement of certainty that British beef was completely safe to eat and that BSE was not transmissible to humans. The way uncertainty was dealt with in this case was the result of a number of factors, including the desire to protect specific stakeholder interests.

One crucial factor was the underlying element of risk political culture in the UK that linked the identity of the actor to the consistency of his policy positions. This led to consistency of position being prioritised over accuracy [Dressel, 2000], and resulted in the government insisting on the absence of risk to the population, maintaining this public position despite mounting evidence to the contrary. Although aware of them, policy-makers chose not to overtly acknowledge the levels of uncertainty and the complexity of the risks involved with BSE and its spread because the ramifications of these were too great for the interests they were trying to safeguard.

B1 Responding to early warnings

The incorporation of rendered meat and bone meal into animal feed creates a number of risks related to the transmission, recycling and amplification of pathogens. Such risks were recognised well before the emergence of BSE. In the US in the mid-1970s, concerns that scrapie may be linked to CJD (although there is no evidence that scrapie is transmissible to humans) led to some regulations being placed on the incorporation of sheep or goat carcasses into human and animal foods [van Zwanenberg & Millstone, 2002:158]. In the UK, too, the Royal Commission on Environmental Pollution recommended in 1979 that minimum processing standards be implemented by the rendering industries in order to minimise the potential for disease spread [RCEP, 1979]. The incoming Thatcher government withdrew these proposed regulations, preferring to let industry decide for itself what standards to use. In retrospect, the failure to act at this point to mitigate the general risk of disease transmission may have had a crucial impact on the later outbreak of BSE, given that the disease “probably originated from a novel source in the early 1970s” [BSE Inquiry, 2000b].

Early warnings that BSE might be transmissible to humans were, in fact, observed by scientists and government officials throughout the period from 1986 (the time of first diagnosis in cattle) to 1995 (when vCJD was first observed in humans). Such observations are noted in, for example, the minutes of a meeting of the National Institute for Biological Standards and Control in May 1988, where the probability of transmission of BSE to humans is assessed as more than remote. The diagnosis in 1990 of a domestic cat with a previously unknown spongiform encephalopathy resembling BSE indicated that the disease could infect a wider range of hosts. Responses to such early warnings of potential dangers to human health were either too weak or came too late. This may have been partly a result of an ‘unwillingness to know’ due to the economic harm this knowledge would cause the UK beef industry (related to deficit A6); and partly due to institutional capacities and procedures (related to deficits B5, 9 and 10).

http://www.irgc.org/IMG/pdf/BSE_full_case_study_web.pdf

Tuesday, July 28, 2009

MAD COW COVER-UP USA MASKED AS SPORADIC CJD

http://madcowtesting.blogspot.com/2009/07/mad-cow-cover-up-usa-masked-as-sporadic.html

SEE THE VIDEO NOW AT THE BOTTOM OF THE BLOG BELOW ;

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

Tuesday, July 14, 2009

U.S. Emergency Bovine Spongiform Encephalopathy Response Plan Summary and BSE Red Book Date: February 14, 2000 at 8:56 am PST

WHERE did we go wrong $$$

http://madcowtesting.blogspot.com/2009/07/us-emergency-bovine-spongiform.html

MY GOD, HOW MANY CASES GOT INTO THE FOOD CHAIN ??? IATROGENIC THERE FROM ??? ATYPICAL BSE MORE VIRULENT, HOW MANY MORE WILL DIE NEEDLESSLY IN THE YEARS AND DECADES TO COME. ...TSS

Friday, December 23, 2011

Oral Transmission of L-type Bovine Spongiform Encephalopathy in Primate Model

Volume 18, Number 1—January 2012 Dispatch

http://transmissiblespongiformencephalopathy.blogspot.com/2011/12/oral-transmission-of-l-type-bovine.html

Wednesday, January 4, 2012

A Bovine Prion Acquires an Epidemic Bovine Spongiform Encephalopathy Strain-Like Phenotype on Interspecies Transmission

http://transmissiblespongiformencephalopathy.blogspot.com/2012/01/bovine-prion-acquires-epidemic-bovine.html

Tuesday, November 15, 2011

Alternative BSE Risk Assessment Methodology of Imported Beef and Beef Offal to Japan Journal of Veterinary Medical Science

Advance Publication

http://transmissiblespongiformencephalopathy.blogspot.com/2011/11/alternative-bse-risk-assessment.html

Monday, January 2, 2012

EFSA Minutes of the 6th Meeting of the EFSA Scientific Network on BSE-TSE Brussels, 29-30 November 2011

http://transmissiblespongiformencephalopathy.blogspot.com/2012/01/efsa-minutes-of-6th-meeting-of-efsa.html

Saturday, June 25, 2011

Transmissibility of BSE-L and Cattle-Adapted TME Prion Strain to Cynomolgus Macaque

"BSE-L in North America may have existed for decades"

http://transmissiblespongiformencephalopathy.blogspot.com/2011/06/transmissibility-of-bse-l-and-cattle.html

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

2011 Monday, September 26, 2011

L-BSE BASE prion and atypical sporadic CJD

http://bse-atypical.blogspot.com/2011/09/l-bse-base-prion-and-atypical-sporadic.html

Owens, Julie

From: Terry S. Singeltary Sr. [flounder9@verizon.net]

Sent: Monday, July 24, 2006 1:09 PM

To: FSIS RegulationsComments

Subject: [Docket No. FSIS-2006-0011] FSIS Harvard Risk Assessment of Bovine Spongiform Encephalopathy (BSE)

Page 1 of 98

http://www.fsis.usda.gov/OPPDE/Comments/2006-0011/2006-0011-1.pdf

FSIS RFEPLY TO TSS ;

Harvard Risk Assessment of Bovine Spongiform Encephalopathy Update, October 31, 2005 INTRODUCTION The United States Department of Agriculture’s Food Safety and Inspection Service (FSIS) held a public meeting on July 25, 2006 in Washington, D.C. to present findings from the Harvard Risk Assessment of Bovine Spongiform Encephalopathy Update, October 31, 2005 (report and model located on the FSIS website:

http://www.fsis.usda.gov/Science/Risk_Assessments/index.asp).

Comments on technical aspects of the risk assessment were then submitted to FSIS. Comments were received from Food and Water Watch, Food Animal Concerns Trust (FACT), Farm Sanctuary, R-CALF USA, Linda A Detwiler, and Terry S. Singeltary. This document provides itemized replies to the public comments received on the 2005 updated Harvard BSE risk assessment. Please bear the following points in mind:

http://www.fsis.usda.gov/PDF/BSE_Risk_Assess_Response_Public_Comments.pdf

Saturday, June 19, 2010

U.S. DENIED UPGRADED BSE STATUS FROM OIE

http://usdameatexport.blogspot.com/2010/06/us-denied-upgraded-bse-status-from-oie.html

Friday, August 20, 2010

USDA: Animal Disease Traceability August 2010

http://naiscoolyes.blogspot.com/2010/08/usda-animal-disease-traceability-august.html

Friday, November 18, 2011

country-of-origin labeling law (COOL) violates U.S. obligations under WTO rules WT/DS384/R WT/DS386/R

http://naiscoolyes.blogspot.com/2011/11/country-of-origin-labeling-law-cool.html

http://naiscoolyes.blogspot.com/

Saturday, April 10, 2010

TOYOTA VS MAD COW DISEASE USA OIE BSE MRR IMPORT AND EXPORT TRADE WARS

http://usdameatexport.blogspot.com/2010/04/toyota-vs-mad-cow-disease-usa-oie-bse.html

TSS

L-BSE BASE prion and atypical sporadic CJD

2011-09-26T09:37:00.000-07:00

Risk.12:

Transmission of Atypical Italian sCJD Case to Humanized Mice Reveals a Novel Infectious Strain

Roberta Galeno,1,† Marco Sbriccoli,1 Loredana Ingrosso,1 Silvia Graziano,1 Angelina Valanzano,1 Anna Poleggi,1 Angela De Pascalis,1 Anna Ladogana,1 Franco Cardone,1 Maria Puopolo,1 Gianluigi Zanusso2 and Maurizio Pocchiari1

1Istituto Superiore di Sanità; Rome, Italy; 2University of Verona; Verona, Italy†Presenting author; Email: roberta.galeno@iss.it

Sporadic Creutzfeldt-Jakob disease (sCJD) is a neurodegenerative prion disorder with uncertain etiology characterized by a typical combination of clinical symptoms, neuropathological lesions, and by the deposition of the pathological protein PrPTSE in the brain.

The vast majority of patients affected by sCJD can be categorized according to the genotype at the polymorphic position www.landesbioscience.com Prion 127

129 of PrP (methionine or valine) and to the molecular mass of PrPTSE (type 1 or 2, corresponding to 21 or 19 kDa), yielding six possible combinations (MM1, MM2, VV1, VV2, MV1, and MV2) that associate with five clinico-pathological variants. Transmission studies of these sCJD subtypes into transgenic mice expressing the human prion protein allowed to identify four different infectious strains, which can partly explain the heterogeneity observed in sCJD patients.1

We recently described a novel molecular and pathological phenotype of sCJD (MV at position 129 of PrP), associated with an unprecedented electrophoretic pattern of PrPTSE characterized by the absence of the highly glycosylated isoform. In this work, we sought to characterize the prion strain associated with this atypical case by intracerebral inoculation into gene-targeted transgenic mice (HuTg) carrying the human PRNP gene with the three 129 genotype combinations. For comparison, three Italian sCJD cases heterozygous at position 129 of the prion protein, belonging to different subtypes (MV1, MV1/2, MV2), were transmitted to the same panel of transgenic mice. Survival times, attack rates, lesion profiles, and molecular analysis of the PrPTSE type recovered from mouse brains injected with the atypical case were compared with data from control animals. Mice inoculated with the atypical case displayed a restricted host tropism, with only a small number of VV animals that resulted PrPTSE-positive after an exceedingly long survival time. Interestingly, PrPTSE accumulated in brains from these mice lacks the diglycosylated band similar to that in sCJD inoculum, yet dissimilar to any other PrPTSE observed in HuTg mice by us and by other authors.1,2 Overall, these results strongly indicate that our atypical case associates with a new infectious strain of sCJD. Further investigations are needed to understand the possible connection with other human and animal prion diseases.

References

1. Bishop MT, Will RG, Manson JC. Defining sporadic Creutzfeldt-Jakob disease strains and their transmission properties. Proc Natl Acad Sci USA 2010; 107:12005-10.

2. Bishop MT, Hart P, Aitchison L, Baybutt HN, Plinston C, Thomson V, et al. Predicting susceptibility and incubation time of human-to-human transmission of vCJD. Lancet Neurol 2006; 5:393-8.

http://www.prion2011.ca/files/PRION_2011_-_Posters_(May_5-11).pdf

Saturday, June 25, 2011

Transmissibility of BSE-L and Cattle-Adapted TME Prion Strain to Cynomolgus Macaque

"BSE-L in North America may have existed for decades"

http://transmissiblespongiformencephalopathy.blogspot.com/2011/06/transmissibility-of-bse-l-and-cattle.html

Sunday, June 26, 2011

Risk Analysis of Low-Dose Prion Exposures in Cynomolgus Macaque

http://transmissiblespongiformencephalopathy.blogspot.com/2011/06/risk-analysis-of-low-dose-prion.html

Thursday, June 23, 2011

Experimental H-type bovine spongiform encephalopathy characterized by plaques and glial- and stellate-type prion protein deposits

http://transmissiblespongiformencephalopathy.blogspot.com/2011/06/experimental-h-type-bovine-spongiform.html

Thursday, July 21, 2011

A Second Case of Gerstmann-Sträussler-Scheinker Disease Linked to the G131V Mutation in the Prion Protein Gene in a Dutch Patient Journal of Neuropathology & Experimental Neurology:

August 2011 - Volume 70 - Issue 8 - pp 698-702

http://transmissiblespongiformencephalopathy.blogspot.com/2011/07/second-case-of-gerstmann-straussler.html

Wednesday, June 15, 2011

Galveston, Texas - Isle port moves through thousands of heifers headed to Russia, none from Texas, Alabama, or Washington, due to BSE risk factor

http://transmissiblespongiformencephalopathy.blogspot.com/2011/06/galveston-texas-isle-port-moves-through.html

Atypical BSE (BASE) Transmitted from Asymptomatic Aging Cattle to a Primate

Emmanuel E. Comoy1*, Cristina Casalone2, Nathalie Lescoutra-Etchegaray1, Gianluigi Zanusso3, Sophie Freire1, Dominique Marcé1, Frédéric Auvré1, Marie-Magdeleine Ruchoux1, Sergio Ferrari3, Salvatore Monaco3, Nicole Salès4, Maria Caramelli2, Philippe Leboulch1,5, Paul Brown1, Corinne I. Lasmézas4, Jean-Philippe Deslys1

1 Institute of Emerging Diseases and Innovative Therapies, CEA, Fontenay-aux-Roses, France, 2 Istituto Zooprofilattico Sperimentale del Piemonte, Turin, Italy, 3 Policlinico G.B. Rossi, Verona, Italy, 4 Scripps Florida, Jupiter, Florida, United States of America, 5 Genetics Division, Brigham & Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America

Abstract Top

Background

Human variant Creutzfeldt-Jakob Disease (vCJD) results from foodborne transmission of prions from slaughtered cattle with classical Bovine Spongiform Encephalopathy (cBSE). Atypical forms of BSE, which remain mostly asymptomatic in aging cattle, were recently identified at slaughterhouses throughout Europe and North America, raising a question about human susceptibility to these new prion strains.

Methodology/Principal Findings

Brain homogenates from cattle with classical BSE and atypical (BASE) infections were inoculated intracerebrally into cynomolgus monkeys (Macacca fascicularis), a non-human primate model previously demonstrated to be susceptible to the original strain of cBSE. The resulting diseases were compared in terms of clinical signs, histology and biochemistry of the abnormal prion protein (PrPres). The single monkey infected with BASE had a shorter survival, and a different clinical evolution, histopathology, and prion protein (PrPres) pattern than was observed for either classical BSE or vCJD-inoculated animals. Also, the biochemical signature of PrPres in the BASE-inoculated animal was found to have a higher proteinase K sensitivity of the octa-repeat region. We found the same biochemical signature in three of four human patients with sporadic CJD and an MM type 2 PrP genotype who lived in the same country as the infected bovine.

Conclusion/Significance

Our results point to a possibly higher degree of pathogenicity of BASE than classical BSE in primates and also raise a question about a possible link to one uncommon subset of cases of apparently sporadic CJD. Thus, despite the waning epidemic of classical BSE, the occurrence of atypical strains should temper the urge to relax measures currently in place to protect public health from accidental contamination by BSE-contaminated products.

Citation: Comoy EE, Casalone C, Lescoutra-Etchegaray N, Zanusso G, Freire S, et al. (2008) Atypical BSE (BASE) Transmitted from Asymptomatic Aging Cattle to a Primate. PLoS ONE 3(8): e3017. doi:10.1371/journal.pone.0003017

Editor: Neil Mabbott, University of Edinburgh, United Kingdom

Received: April 24, 2008; Accepted: August 1, 2008; Published: August 20, 2008

Copyright: © 2008 Comoy et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Funding: This work has been supported by the Network of Excellence NeuroPrion.

Competing interests: CEA owns a patent covering the BSE diagnostic tests commercialized by the company Bio-Rad.

* E-mail: emmanuel.comoy@cea.fr

http://www.plosone.org/article/info:doi%2F10.1371%2Fjournal.pone.0003017

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

Saturday, August 14, 2010

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

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

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

P.9.21

Molecular characterization of BSE in Canada

Jianmin Yang1, Sandor Dudas2, Catherine Graham2, Markus Czub3, Tim McAllister1, Stefanie Czub1 1Agriculture and Agri-Food Canada Research Centre, Canada; 2National and OIE BSE Reference Laboratory, Canada; 3University of Calgary, Canada

Background: Three BSE types (classical and two atypical) have been identified on the basis of molecular characteristics of the misfolded protein associated with the disease. To date, each of these three types have been detected in Canadian cattle.

Objectives: This study was conducted to further characterize the 16 Canadian BSE cases based on the biochemical properties of there associated PrPres. Methods: Immuno-reactivity, molecular weight, glycoform profiles and relative proteinase K sensitivity of the PrPres from each of the 16 confirmed Canadian BSE cases was determined using modified Western blot analysis.

Results: Fourteen of the 16 Canadian BSE cases were C type, 1 was H type and 1 was L type. The Canadian H and L-type BSE cases exhibited size shifts and changes in glycosylation similar to other atypical BSE cases. PK digestion under mild and stringent conditions revealed a reduced protease resistance of the atypical cases compared to the C-type cases. N terminal- specific antibodies bound to PrPres from H type but not from C or L type. The C-terminal-specific antibodies resulted in a shift in the glycoform profile and detected a fourth band in the Canadian H-type BSE.

Discussion: The C, L and H type BSE cases in Canada exhibit molecular characteristics similar to those described for classical and atypical BSE cases from Europe and Japan. This supports the theory that the importation of BSE contaminated feedstuff is the source of C-type BSE in Canada. *It also suggests a similar cause or source for atypical BSE in these countries.

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

NOW, LET'S LOOK AT A FEW 100S OF TONS OF THESE BANNED SUSPECT MAD COW FEED IN COMMERCE IN THE USA ;

BANNED SUSPECT MAD COW FEED IN COMMERCE 2006-2007, SOME 10 YEARS AFTER THE INFAMOUS PARTIAL AND VOLUNTARY MAD COW FEED BAN or August 4, 1997, that was nothing more than ink on paper, so really, there was no BSE triple fire wall at all, and this was improving ???

*** BANNED MAD COW FEED IN THE USA IN COMMERCE TONS AND TONS

THIS is just ONE month report, of TWO recalls of prohibited banned MBM, which is illegal, mixed with 85% blood meal, which is still legal, but yet we know the TSE/BSE agent will transmit blood. we have this l-BSE in North America that is much more virulent and there is much concern with blood issue and l-BSE as there is with nvCJD in humans. some are even starting to be concerned with sporadic CJD and blood, and there are studies showing transmission there as well. ... this is one month recall page, where 10 MILLION POUNDS OF BANNED MAD COW FEED WENT OUT INTO COMMERCE, TO BE FED OUT. very little of the product that reaches commerce is ever returned via recall, very, very little. this was 2007, TEN YEARS AFTER THE AUGUST 4, 1997, PARTIAL AND VOLUNTARY MAD COW FEED BAN IN THE USA, that was nothing but ink on paper. i have listed the tonnage of mad cow feed that was in ALABAMA in one of the links too, this is where the infamous g-h-BSEalabama case was, a genetic relation matching the new sporadic CJD in the USA. seems this saga just keeps getting better and better.......$$$

10,000,000+ LBS. of PROHIBITED BANNED MAD COW FEED I.E. BLOOD LACED MBM IN COMMERCE USA 2007

Date: March 21, 2007 at 2:27 pm PST

RECALLS AND FIELD CORRECTIONS: VETERINARY MEDICINES -- CLASS II

___________________________________

PRODUCT

Bulk cattle feed made with recalled Darling's 85% Blood Meal, Flash Dried, Recall # V-024-2007

CODE

Cattle feed delivered between 01/12/2007 and 01/26/2007

RECALLING FIRM/MANUFACTURER

Pfeiffer, Arno, Inc, Greenbush, WI. by conversation on February 5, 2007.

Firm initiated recall is ongoing.

REASON

Blood meal used to make cattle feed was recalled because it was cross- contaminated with prohibited bovine meat and bone meal that had been manufactured on common equipment and labeling did not bear cautionary BSE statement.

VOLUME OF PRODUCT IN COMMERCE

42,090 lbs.

DISTRIBUTION

WI

___________________________________

PRODUCT

Custom dairy premix products: MNM ALL PURPOSE Pellet, HILLSIDE/CDL Prot- Buffer Meal, LEE, M.-CLOSE UP PX Pellet, HIGH DESERT/ GHC LACT Meal, TATARKA, M CUST PROT Meal, SUNRIDGE/CDL PROTEIN Blend, LOURENZO, K PVM DAIRY Meal, DOUBLE B DAIRY/GHC LAC Mineral, WEST PIONT/GHC CLOSEUP Mineral, WEST POINT/GHC LACT Meal, JENKS, J/COMPASS PROTEIN Meal, COPPINI - 8# SPECIAL DAIRY Mix, GULICK, L-LACT Meal (Bulk), TRIPLE J - PROTEIN/LACTATION, ROCK CREEK/GHC MILK Mineral, BETTENCOURT/GHC S.SIDE MK-MN, BETTENCOURT #1/GHC MILK MINR, V&C DAIRY/GHC LACT Meal, VEENSTRA, F/GHC LACT Meal, SMUTNY, A- BYPASS ML W/SMARTA, Recall # V-025-2007

CODE

The firm does not utilize a code - only shipping documentation with commodity and weights identified.

RECALLING FIRM/MANUFACTURER

Rangen, Inc, Buhl, ID, by letters on February 13 and 14, 2007. Firm initiated recall is complete.

REASON

Products manufactured from bulk feed containing blood meal that was cross contaminated with prohibited meat and bone meal and the labeling did not bear cautionary BSE statement.

VOLUME OF PRODUCT IN COMMERCE

9,997,976 lbs.

DISTRIBUTION

ID and NV

END OF ENFORCEMENT REPORT FOR MARCH 21, 2007

http://www.fda.gov/Safety/Recalls/EnforcementReports/2007/ucm120446.htm

Saturday, November 6, 2010

TAFS1 Position Paper on Position Paper on Relaxation of the Feed Ban in the EU Berne, 2010 TAFS

INTERNATIONAL FORUM FOR TRANSMISSIBLE ANIMAL DISEASES AND FOOD SAFETY a non-profit Swiss Foundation

http://madcowfeed.blogspot.com/2010/11/tafs1-position-paper-on-position-paper.html

Archive Number 20101206.4364 Published Date 06-DEC-2010

Subject PRO/AH/EDR & Prion disease update 2010 (11)

PRION DISEASE UPDATE 2010 (11)

http://www.promedmail.org/direct.php?id=20101206.4364

Saturday, July 23, 2011

CATTLE HEADS WITH TONSILS, BEEF TONGUES, SPINAL CORD, SPECIFIED RISK MATERIALS (SRM's) AND PRIONS, AKA MAD COW DISEASE

http://transmissiblespongiformencephalopathy.blogspot.com/2011/07/cattle-heads-with-tonsils-beef-tongues.html

Wednesday, March 31, 2010

Atypical BSE in Cattle

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

In addition, non-human primates are specifically susceptible for atypical BSE as demonstrated by an approximately 50% shortened incubation time for L-type BSE as compared to C-type. Considering the current scientific information available, it cannot be assumed that these different BSE types pose the same human health risks as C-type BSE or that these risks are mitigated by the same protective measures.

This study will contribute to a correct definition of specified risk material (SRM) in atypical BSE. The incumbent of this position will develop new and transfer existing, ultra-sensitive methods for the detection of atypical BSE in tissue of experimentally infected cattle.

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

Thursday, August 12, 2010

Seven main threats for the future linked to prions

First threat

The TSE road map defining the evolution of European policy for protection against prion diseases is based on a certain numbers of hypotheses some of which may turn out to be erroneous. In particular, a form of BSE (called atypical Bovine Spongiform Encephalopathy), recently identified by systematic testing in aged cattle without clinical signs, may be the origin of classical BSE and thus potentially constitute a reservoir, which may be impossible to eradicate if a sporadic origin is confirmed.

***Also, a link is suspected between atypical BSE and some apparently sporadic cases of Creutzfeldt-Jakob disease in humans. These atypical BSE cases constitute an unforeseen first threat that could sharply modify the European approach to prion diseases.

Second threat

snip...

http://www.neuroprion.org/en/np-neuroprion.html

Rural and Regional Affairs and Transport References Committee

The possible impacts and consequences for public health, trade and agriculture of the Government's decision to relax import restrictions on beef Final report June 2010

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

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

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

[Terry S. Singeltary Sr. has added the following comment:

"According to the World Health Organisation, the future public health threat of vCJD in the UK and Europe and potentially the rest of the world is of concern and currently unquantifiable. However, the possibility of a significant and geographically diverse vCJD epidemic occurring over the next few decades cannot be dismissed.

http://whqlibdoc.who.int/publications/2003/9241545887.pdf

Terry S. Singeltary Sr. has added the following comment:

"According to the World Health Organisation, the future public health threat of vCJD in the UK and Europe and potentially the rest of the world is of concern and currently unquantifiable. However, the possibility of a significant and geographically diverse vCJD epidemic occurring over the next few decades cannot be dismissed.

The key word here is diverse. What does diverse mean? If USA scrapie transmitted to USA bovine does not produce pathology as the UK c-BSE, then why would CJD from there look like UK vCJD?"

http://www.promedmail.org/direct.php?id=20100405.1091

When L-type BSE was inoculated into ovine transgenic mice and Syrian hamster the resulting molecular fingerprint had changed, either in the first or a subsequent passage, from L-type into C-type BSE. In addition, non-human primates are specifically susceptible for atypical BSE as demonstrated by an approximately 50% shortened incubation time for L-type BSE as compared to C-type. Considering the current scientific information available, it cannot be assumed that these different BSE types pose the same human health risks as C-type BSE or that these risks are mitigated by the same protective measures.

This study will contribute to a correct definition of specified risk material (SRM) in atypical BSE. The incumbent of this position will develop new and transfer existing, ultra-sensitive methods for the detection of atypical BSE in tissue of experimentally infected cattle.

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

The conclusions state that, at present, the only TSE agent demonstrated to be zoonotic is the classical BSE agent. Active screening has allowed the identification of 3 new forms of animal TSEs (H-type atypical BSE, L-type atypical BSE, and atypical scrapie), but the information obtained has major limitations due to the unknown sensitivity of the current monitoring system for these TSEs. There is no epidemiological evidence to suggest that classical scrapie is zoonotic. The epidemiological data are too limited to conclude whether the atypical scrapie agent has a zoonotic potential. Transmission experiments to human PrP transgenic mice or primates suggest that some TSE agents other than the classical BSE agent in cattle (namely L-type atypical BSE, classical BSE in sheep, TME, CWD agents) might have zoonotic potential and indicate that that of the L-type atypical BSE agent appears similar or even higher than that of the classical BSE agent. A single study reported efficient transmission of a natural sheep classical scrapie isolate to primates.

Commentary ---------- Following to a request from the European Commission, the Panel on Biological Hazards (BIOHAZ) and the European Centre for Disease Prevention and Control (ECDC) were asked to deliver a scientific opinion on any possible epidemiological or molecular association between transmissible spongiform encephalopathies (TSEs) in animals and humans. The opinion reviews and discusses the existing scientific evidence that links animal and human TSEs currently known.

The opinion first considers the definition of zoonoses and the principles for the identification of zoonotic diseases, which can be based on evidence gathered from both epidemiological and laboratory studies. The opinion describes the challenges involved in identifying TSEs as zoonoses, due to the specific characteristics of TSE infections/diseases, such as the nature of TSE agents, the occurrence of animal and human TSEs, and the type of monitoring applied, the long incubation period of TSEs etc. The example of the process that led to establishing a link between bovine spongiform encephalopathy (BSE) and variant Creutzfeldt-Jakob disease (vCJD) is reviewed. The epidemiological and laboratory criteria that can be used to investigate such a link are described in detail, since those criteria might be useful for the identification of links between other animal and human TSEs.

The opinion discusses the strain diversity of the TSE agents described in sheep, goats, cattle, cervids, and humans, based on the current knowledge, which highlights that multiple TSE agents exist in each species. The factors influencing the capacity of TSE agents to cross the species transmission barrier are then considered in detail, including the variability in host and donor PrP gene and protein, the TSE strain type involved and its interaction with the host PrP, and the route of infection.

The opinion critically assesses the tools and methodologies currently available to study and evaluate the possible association between animal and human TSEs. The use of epidemiology is discussed for TSEs in both animals and humans, and the possibility to compare the 2 sources of information is presented as a possible method to study the possible links.

Both in vivo and in vitro laboratory methods are considered and discussed, including neuropathology, transmission experiments involving different animal models (wild type and transgenic mice, primates and other species), biochemical methods, cell-free conversion assays, protein misfolding cyclic amplification (PMCA), and cell culture assays. Characteristics, advantages, and disadvantages of the different methods are reviewed, including the opportunity to collate data from different types of experiments for the study of potential associations between animal and human TSEs.

The opinion then reviews the scientific evidence currently available for the different animal and human TSEs, including classical BSE, atypical BSE (H-type and L-type), classical scrapie, atypical scrapie, chronic wasting disease (CWD), transmissible mink encephalopathy (TME), and human TSEs. In particular, the following aspects are systematically discussed for each TSE agent: epidemiology, pathogenesis, and in vivo and in vitro transmission experiments.

The opinion concludes that, at present, the only TSE agent demonstrated to be zoonotic is the classical BSE agent. With regard to human TSEs, detected cases of sporadic CJD are randomly distributed in time and geographical location. These observations have been interpreted as a supportive argument that sporadic CJD is not environmentally acquired. However, the epidemiological evidence in relation to sporadic CJD cannot be regarded as definitive, and the possibility that a small proportion of cases are zoonotic cannot be excluded.

It also concludes that a series of uncertainties in relation to the epidemiological patterns of animal and human TSEs indicate that even a rough comparison of the present epidemiological patterns of human and animal TSEs other than classical BSE is unlikely to be informative. Because of these uncertainties, it is an imperative to continue to carry out systematic surveillance of human TSE diseases, and to continue and improve the surveillance of animal TSE diseases.

The opinion highlights that the active screening has allowed the identification of 3 new forms of animal TSEs (L-type atypical BSE, H-type atypical BSE, and atypical scrapie), but that the information obtained has major limitations due to the unknown sensitivity of the current monitoring system for these TSEs.

There is no epidemiological evidence to suggest that classical scrapie is zoonotic. The epidemiological data are too limited to conclude whether the atypical scrapie agent has a zoonotic potential.

Transmission experiments to human PrP transgenic mice suggest that some TSE agents other than the classical BSE agent in cattle (namely L-type atypical BSE and classical BSE in sheep agents) might have zoonotic potential, whereas for other agents there is no evidence provided of a zoonotic potential (H-type atypical BSE and CWD), or no published studies are available (classical and atypical scrapie). In addition, transmission experiments to primates suggest that some TSE agents other than the classical BSE agent in cattle (namely L-type atypical BSE, classical BSE in sheep, TME, CWD agents) might have zoonotic potential. In particular, primates are highly permissive to L-type atypical BSE, even by the oral route.

The opinion emphasizes that laboratory transmission experiments indicate that the L-type atypical BSE agent has a significant zoonotic potential, which appears similar or even higher than that of the classical BSE agent. While transmission data for evaluating the zoonotic potential of classical scrapie in primates and human PrP transgenic mice are extremely limited or not yet available, a single study reported efficient transmission of a natural sheep classical scrapie isolate to primates.

The opinion concludes that human PrP transgenic mice and primates are currently the most relevant models for investigating the human transmission barrier, but the extent to which such models are informative for measuring the zoonotic potential of an animal TSE under field exposure conditions is unknown. It is unpredictable whether a TSE agent will transmit to a new host, and if the transmission principally occurs, what the transmission rate will be.

Based on the results obtained with in vitro conversion assays, the opinion concludes that there is probably no absolute molecular barrier to transmission of TSE agents between mammalian species. Results also suggest that these assays may be developed as a tool for quantifying the transmission barriers between species for different TSE agent strains; however, there is no means at the moment to transpose in vitro results into the likelihood of in vivo interspecies transmission.

-- Communicated by: Terry S Singeltary Sr

[ProMED-mail thanks Terry S Singeltary Sr for drawing attention to this comprehensive document which provides a current evaluation of experimental work designed to explore the zoonotic potential of the various recently recognised TSEs of domestic and other animals.

It is concluded that at present the only TSE agent demonstrated to be zoonotic is the classical BSE agent. Nor can it be entirely excluded at the present time that a small proportion of cases of sporadic CJD may be environmentally acquired. - Mod.CP]

******

http://www.promedmail.org/direct.php?id=20110607.1736

14th ICID International Scientific Exchange Brochure -

Final Abstract Number: ISE.114

Session: International Scientific Exchange

Transmissible Spongiform encephalopathy (TSE) animal and human TSE in North America update October 2009

T. Singeltary

Bacliff, TX, USA

Background:

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.

Methods:

12 years independent research of available data

Results:

I propose that the current diagnostic criteria for human TSEs only enhances and helps the spreading of human TSE from the continued belief of the UKBSEnvCJD only theory in 2009. With all the science to date refuting it, to continue to validate this old myth, will only spread this TSE agent through a multitude of potential routes and sources i.e. consumption, medical i.e., surgical, blood, dental, endoscopy, optical, nutritional supplements, cosmetics etc.

Conclusion:

I would like to submit a review of past CJD surveillance in the USA, and the urgent need to make all human TSE in the USA a reportable disease, in every state, of every age group, and to make this mandatory immediately without further delay. The ramifications of not doing so will only allow this agent to spread further in the medical, dental, surgical arena's. Restricting the reporting of CJD and or any human TSE is NOT scientific. Iatrogenic CJD knows NO age group, TSE knows no boundaries. I propose as with Aguzzi, Asante, Collinge, Caughey, Deslys, Dormont, Gibbs, Gajdusek, Ironside, Manuelidis, Marsh, et al and many more, that the world of TSE Transmissible Spongiform Encephalopathy is far from an exact science, but there is enough proven science to date that this myth should be put to rest once and for all, and that we move forward with a new classification for human and animal TSE that would properly identify the infected species, the source species, and then the route.

http://ww2.isid.org/Downloads/14th_ICID_ISE_Abstracts.pdf

Monday, May 23, 2011

Atypical Prion Diseases in Humans and Animals 2011

Top Curr Chem (2011)

DOI: 10.1007/128_2011_161

# Springer-Verlag Berlin Heidelberg 2011

Michael A. Tranulis, Sylvie L. Benestad, Thierry Baron, and Hans Kretzschmar

Abstract

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

M.A. Tranulis (*)

Norwegian School of Veterinary Science, Oslo, Norway

e-mail: Michael.Tranulis@nvh.no

S.L. Benestad

Norwegian Veterinary Institute, Oslo, Norway

T. Baron

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

H. Kretzschmar

Ludwig-Maximilians University of Munich, Munich, Germany

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

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

snip...SEE MORE HERE ;

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

Sunday, September 25, 2011

Clinical Heidenhain Variant Of Sporadic Creutzfeldt-Jakob Disease (CJD) With Co-occurrence Of Prion Protein Types 1 and 2

http://creutzfeldt-jakob-disease.blogspot.com/2011/09/clinical-heidenhain-variant-of-sporadic.html

Saturday, March 5, 2011

MAD COW ATYPICAL CJD PRION TSE CASES WITH CLASSIFICATIONS PENDING ON THE RISE IN NORTH AMERICA

http://transmissiblespongiformencephalopathy.blogspot.com/2011/03/mad-cow-atypical-cjd-prion-tse-cases.html

Thursday, August 4, 2011

Terry Singeltary Sr. on the Creutzfeldt-Jakob Disease Public Health Crisis, Date aired: 27 Jun 2011

http://transmissiblespongiformencephalopathy.blogspot.com/2011/08/terry-singeltary-sr-on-creutzfeldt.html

Mad Cow Scaremongers

Mad Cow Scaremongers by Terry S. Singeltary Sr. a review of the TSE prion agent 2003-2011

http://transmissiblespongiformencephalopathy.blogspot.com/2011/09/mad-cow-scaremongers.html

TSS

Neuroanatomical Distribution of Disease-Associated Prion Protein in Cases of Bovine Spongiform Encephalopathy Detected by Fallen Stock Surveillance in Japan

2011-07-19T14:11:00.000-07:00

Neuroanatomical Distribution of Disease-Associated Prion Protein in Cases of Bovine Spongiform Encephalopathy Detected by Fallen Stock Surveillance in Japan

Hiroyuki OKADA1), Yoshihumi IWAMARU1), Morikazu IMAMURA1), Kentaro MASUJIN1), Yuichi MATSUURA1), Yoshihisa SHIMIZU1), Kazuo KASAI1), Masuhiro TAKATA1), Shigeo FUKUDA2), Satoshi NIKAIDO2), Kei FUJII2), Sadao ONOE2), Shirou MOHRI1) and Takashi YOKOYAMA1)

1) Prion Disease Research Center, National Institute of Animal Health 2) Hokkaido Animal Research Center, Hokkaido Research Organization

(Received 15-Jun-2011) (Accepted 2-Jul-2011)

ABSTRACT.

Bovine spongiform encephalopathy (BSE) is a fatal neurodegenerative disorder of cattle characterized by accumulation of the disease-associated prion protein (PrPSc) in the central nervous system (CNS). The immunohistochemical patterns and distribution of PrPSc were investigated in the CNS, brains, and spinal cords of 7 naturally occurring BSE cases confirmed by the fallen stock surveillance program in Japan. No animals showed characteristic clinical signs of the disease. Coronal slices of 14 different brain areas in each case were immunohistochemically analyzed using an anti-prion protein antibody. Immunolabeled PrPSc deposition was widely observed throughout each brain and spinal cord. Intense PrPSc deposition was greater in the thalamus, brainstem, and spinal cord of the gray matter than in the neocortices. The topographical distribution pattern and severity of PrPSc accumulation were mapped and plotted as immunohistochemical profiles of the different brain areas along the caudal-rostral axis of the brain. The distribution pattern and severity of the immunolabeled PrPSc in the CNS were almost the same among the 7 cases analyzed, suggesting that the naturally occurring cases in this study were at the preclinical stage of the disease. Immunohistochemical mapping of the PrPSc deposits will be used to clarify the different stages of BSE in cattle.

KEY WORDS: BSE, cattle, immunohistochemistry, prion

SNIP...

DISCUSSION

Levels and regional tropism of vacuolar changes, namely the lesion profile in the brain, is considered a reliable indicator for histopathological diagnosis of BSE-affected cattle [26, 32]. However, optimal preservation is required to ensure the identification of vacuolar changes in certain areas of the brainstem devoid of artifactual vacuolations induced by a postmortem delay of tissue sampling that led to autolysis. Although autolysis conditions have been usually encountered in field cases of BSE diagnosis, autolysis and the frozen condition do not significantly influence PrPSc detection by immunohistochemistry [4, 6, 7, 18]. Moreover, PrPSc immunohistochemistry is an essential tool and may contribute to our understanding of the pathogenesis of BSE [6, 12].

All cattle in the present study were field BSE cases confirmed by the fallen stock surveillance program in Japan. Despite the limited number of animals and differences in their ages and breeds, PrPSc topographical distributions and types in the brain were remarkably similar among these cases and to those in published reports in BSE cattle [5, 13, 15, 16, 20, 27, 30]. The severity of PrPSc deposition was variable in

12

the brain regions. Large amounts of PrPSc deposits were present in the brainstem and thalamus, whereas the cerebral cortices and hippocampus were less involved, suggesting that PrPSc accumulation in the brain of BSE-affected cattle is related to area-dependent tropism [5, 30]. These results indicate that most BSE cases that occur in Japan have been caused by a single infectious agent strain identical to the C-BSE prion. Moreover, the lack of apparent differences in PrPSc distribution patterns or deposition intensity among the 7 cases in this study might suggest the same clinical stage of the disease. A greater degree of PrPSc accumulation within the thalamus and brainstem of all animals was obvious compared to the slaughtered cases in Japan that seemed to be at the preclinical stage of the disease [13]. The present cases revealed no clinical signs or symptoms relevant to BSE, but some cases exhibited dystasia. These results might indicate that the 2 BSE cases with the locomotive disability were highly likely to be at an early clinical stage of the disease.

Recently, other phenotypes, namely atypical BSE that differs from C-BSE, have been reported among BSE cases in Europe [2, 21], North America [23] and Japan [11, 34]. Atypical BSE cases are temporally classified into 2 types, namely L- and H-types according to the molecular size of the proteinases K-digested nonglycosylated form of PrPSc [14, 21]. The immunolabeled PrPSc distribution patterns and/or types in the brains of cattle affected with L-BSE [3, 17] and H-BSE [23] differed from those with C-BSE. C-BSE was characterized the presence of stellate and intraneuronal immunolabeled PrPSc [17, 27]. Stellate PrPSc deposition was located mainly in the gray matter neuropils of the cerebral and cerebellar cortices [27] and was reported to deposit to astrocytes stained with glial fibrillary acidic protein [30]. Additionally, coarse granular and coalescing PrPSc deposition was mainly distributed in the brainstem in the

13

present cases as described in an report [30]. On the other hand, a differential PrPSc deposition pattern was detected in atypical BSE cases. L-BSE showed abundant amyloid PrP-plaques and perineural PrPSc in the brain [3, 17]. PrP-positive amyloid plaques up to 25 μm in diameter were present in an atypical BSE case in Japan (BSE/JP24). In the 7 cases studied here, no PrP-positive plaques were demonstrated in the brain. However, it has been reported that plaque-like PrPSc stained with Congo red rarely appeared in the thalamic nuclei of C-BSE–affected cattle [5, 33]. Additionally, in a Swedish H-BSE case, no stellate PrPSc deposits were identified [8]. Therefore, immunohistochemical profile and mapping of the pathologic stage of the disease and confirmation of the infectious agent strain, e.g., C-BSE or atypical BSE [30].

In summary, the types and distribution patterns of immunolabeled PrPSc in the brain and spinal cords of the 7 naturally occurring BSE cases confirmed by the fallen stock surveillance program in Japan were in accordance with published C-BSE cases, indicating that the BSE in the affected animals reported here was caused by a single infectious agent strain identical to the C-BSE prion.

[PDF (934K)]

doi:10.1292/jvms.11-0291 JOI JST.JSTAGE/jvms/11-0291

Copyright(c) 2011 by the Japanese Society of Veterinary Science

http://www.jstage.jst.go.jp/article/jvms/advpub/0/1107110572/_pdf

Bio.040: Phenotypic Variability of Italian BASE Affected Cattle

Cristiano Corona,1,† Chiara Porcario,1 Elena Vallino Costassa,1 Maria Mazza,1 Francesca Martucci,1 Barbara Iulini,1 Marina Gallo,1 Franco Paterlini,2 Maria N. Chieppa,1 Luana Dell’Atti,1 Cristiana Maurella,1 Simone Peletto,1 Pierluigi Acutis,1 Maria Caramelli,1 Gianluigi Zanusso3 and Cristina Casalone1

1Istituto Zooprofilattico Sperimentale del Piemonte Liguria e Valle d’Aosta; Turin, Italy; 2Istituto Zooprofilattico Sperimentale della Lombardia e dell’Emilia Romagna; Bergamo, Italy; 3Università di Verona, Policlinico GB Rossi; Verona, Italy†Presenting author; Email: cristiano.corona@izsto.it

In Italy, in the framework of BSE surveillance program, 145 cases of the disease have been identified so far. Out of 145 BSE positive cases, five cattle were L-type BSE forms, according to the lower electrophoretic migration and the mono-glycosylated dominant glycotype of protease resistant PrP (PrPSc), distinct from classical BSE (C-BSE).

The first three Italian L-type BSE cases were defined "BASE" (bovine amyloidotic spongiform encephalopathy) cases, since the immunohistochemistry showed PrP amyloid deposits in the brain tissue mainly localized in the white matter of thalamus and forebrain areas. Unfortunately, in the fourth Italian L-type case brain sampling was restricted to the brainstem with no evidence of amyloid deposits and the definition of BASE was precluded.

The fifth L-type BSE case was recently confirmed in a 14-year-old regularly slaughtered Alpine Brown cattle free of neurological signs. Immunoblot analysis showed the BSE L-type PrPSc, as in all other four Italian cases. However, in contrast to what observed in the other BASE cases, PrPSc was mainly distributed in the obex compare to the more rostral brain regions. These results were confirmed also by immunohistochemistry (IHC). Furthermore, PrP deposition pattern in the obex was granular and punctate, resembling what we usually observe in C-BSE. Unexpectedly, no PrPSc amyloid plaques were observed but only small scattered PrPSc aggregates in the thalamus as well as in the forebrain. Genetic analysis of the PRNP coding sequence revealed a genotype similar to that of the other atypical cases detected so far, suggesting that an association between the PrP amino acid composition and the observed phenotype should be excluded.

Despite all atypical BSE cases were L-type BSE the neuropathological phenotype showed a slight variability. These differences highlighted might be not related to the animal age, breed or PRNP but to a different stage of the disease. To date, all data indicate that BASE is a sporadic disease in cattle and that disease modifiers, other than those investigated might influence the disease phenotype.

Risk.16: Clinical Disease in Cattle Experimentally Inoculated with All Types of BSE

Catherine Graham,1,† Michel Levy,2 Ed Pajor,2 Garth McGregor,1 Rheana Flitton1 and Stefanie Czub1

1Canadian Food Inspection Agency; Lethbridge, AB Canada; 2Faculty of Veterinary Medicine; University of Calgary; Calgary, AB Canada†Presenting author; Email: catherine.graham@inspection.gc.ca

Background. Classical, or C-type, bovine spongiform encephalopathy (BSE) has been extensively described in the literature. Recently, two novel forms of BSE, termed atypical BSE, have been reported in a number of countries. These new forms show differences in the biochemical characteristics of the prion protein and, where reported, tend to occur in aged animals but descriptions of clinical presentation are incomplete or absent.

Materials and Methods. Female Hereford/Angus cross calves were intracranially challenged at approximately five months of age with 1 ml of a 10% brain homogenate originating from Canadian field cases of BSE which had been previously classified as C-, L-, or H- type.

The animals were monitored during incubation period, and clinical disease is described using a standardized examination protocol. Incubation period, description and progression of clinical signs was recorded and videotaped for objective evaluation.

Results. All L- and H- type atypical BSE challenged animals began to display signs of clinical disease at approximately 11 months post inoculation, and disease progression was slow but constant until animals were euthanized. Clinical signs in all atypical BSE inoculated animals included hesitation at doors and gates, spontaneous muscle fasciculations and sensitivity to touch. Teeth grinding and excessive salivation are occasionally noted. Animals with L-type BSE are very anxious and show high levels of sensitivity to hand movement. One H-type animal shows periods of somnolence. Both H-type inoculated animals go down during handling and have difficulty rising and show sensitivity to movement around their head and neck area, but to a lesser degree than the L-type BSE inoculated animals. Interestingly, no locomotor abnormalities have been observed in either group.

C-type challenged animals remain normal at approximately 18 months post inoculation. Clinical disease in C-type inoculated animals from a previous transmission study was typically slow and intermittently displayed during the initial stages and after a period of two to four months was more consistent and progressive. Clinical signs in C-type BSE were as previously reported in the literature.

Discussion. The spectrum of clinical signs for all three types of BSE examined is similar. Incubation period is shorter for H- and L-type BSE as compared with C-type. Once clinical signs begin, progression is slow but relentless in atypical BSE, and more insidious in classical BSE. A summary of clinical signs presented in the three different types of BSE will be presented, and video of clinical disease will be displayed.

http://www.prion2011.ca/files/PRION_2011_-_Posters_(May_5-11).pdf

Thursday, June 23, 2011

Experimental H-type bovine spongiform encephalopathy characterized by plaques and glial- and stellate-type prion protein deposits

http://transmissiblespongiformencephalopathy.blogspot.com/2011/06/experimental-h-type-bovine-spongiform.html

Journal of Clinical Microbiology, June 2011,p. 2109-2115, Vol. 49, No. 6 0095-1137/11/$12.00+0 doi:10.1128/JCM.02033-10

Distinct Proteinase K-Resistant Prion Protein Fragment in Goats with No Signs of Disease in a Classical Scrapie Outbreak

Ilias G. Bouzalas1,, Florian Lörtscher3,, Chrysostomos I. Dovas1, Anna Oevermann3, Jan P. M. Langeveld2, Maria Papanastassopoulou1, Orestis Papadopoulos1, Andreas Zurbriggen3 and Torsten Seuberlich3*

Aristotle University of Thessaloniki, Thessaloniki, Greece,1 Central Veterinary Institute of Wageningen UR, Lelystad, Netherlands,2 University of Berne, Berne, Switzerland3

Received 8 October 2010/ Returned for modification 26 November 2010/ Accepted 19 March 2011

Considerable efforts have been directed toward the identification of small-ruminant prion diseases, i.e., classical and atypical scrapie as well as bovine spongiform encephalopathy (BSE). Here we report the in-depth molecular analysis of the proteinase K-resistant prion protein core fragment (PrPres) in a highly scrapie-affected goat flock in Greece. The PrPres profile by Western immunoblotting in most animals was that of classical scrapie in sheep. However, in a series of clinically healthy goats we identified a unique C- and N-terminally truncated PrPres fragment, which is akin but not identical to that observed for atypical scrapie. These findings reveal novel aspects of the nature and diversity of the molecular PrPres phenotypes in goats and suggest that these animals display a previously unrecognized prion protein disorder.

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

* Corresponding author. Mailing address: NeuroCentre, DCR-VPH, Bremgartenstrasse 109a, CH-3001 Berne, Switzerland. Phone: 41 31 631 2206. Fax: 41 31 631 2538. E-mail: torsten.seuberlich@itn.unibe.ch .

I.G.B. and F.L. contributed equally to this study.

Supplemental material for this article may be found at http://jcm.asm.org/.

Published ahead of print on 30 March 2011.

http://jcm.asm.org/cgi/content/abstract/49/6/2109

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

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

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

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

Thursday, November 18, 2010

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

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

Sunday, October 3, 2010

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

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

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

FROM THE STUDY ;

Neuroanatomical Distribution of Disease-Associated Prion Protein in Cases of Bovine Spongiform Encephalopathy Detected by Fallen Stock Surveillance in Japan

"Although autolysis conditions have been usually encountered in field cases of BSE diagnosis, autolysis and the frozen condition do not significantly influence PrPSc detection by immunohistochemistry [4, 6, 7, 18]."

maybe that's why the USDA et al likes to use it ;

Completely Edited Version

PRION ROUNDTABLE

2003

Dr. Linda Detwiler

THE IHC test has been proven to be the LEAST LIKELY to detect BSE/TSE in the bovine, and these were probably from the most high risk cattle pool, the ones the USDA et al, SHOULD have been testing. ...TSS

USDA 2003

We have to be careful that we don't get so set in the way we do things that we forget to look for different emerging variations of disease. We've gotten away from collecting the whole brain in our systems. We're using the brain stem and we're looking in only one area. In Norway, they were doing a project and looking at cases of Scrapie, and they found this where they did not find lesions or PRP in the area of the obex. They found it in the cerebellum and the cerebrum. It's a good lesson for us. Ames had to go back and change the procedure for looking at Scrapie samples. In the USDA, we had routinely looked at all the sections of the brain, and then we got away from it. They've recently gone back. Dr. Keller: Tissues are routinely tested, based on which tissue provides an 'official' test result as recognized by APHIS.

Dr. Detwiler: That's on the slaughter. But on the clinical cases, aren't they still asking for the brain? But even on the slaughter, they're looking only at the brainstem. We may be missing certain things if we confine ourselves to one area.

snip.............

Dr. Detwiler: It seems a good idea, but I'm not aware of it. Another important thing to get across to the public is that the negatives do not guarantee absence of infectivity. The animal could be early in the disease and the incubation period. Even sample collection is so important. If you're not collecting the right area of the brain in sheep, or if collecting lymphoreticular tissue, and you don't get a good biopsy, you could miss the area with the PRP in it and come up with a negative test. There's a new, unusual form of Scrapie that's been detected in Norway. We have to be careful that we don't get so set in the way we do things that we forget to look for different emerging variations of disease. We've gotten away from collecting the whole brain in our systems. We're using the brain stem and we're looking in only one area. In Norway, they were doing a project and looking at cases of Scrapie, and they found this where they did not find lesions or PRP in the area of the obex. They found it in the cerebellum and the cerebrum. It's a good lesson for us. Ames had to go back and change the procedure for looking at Scrapie samples. In the USDA, we had routinely looked at all the sections of the brain, and then we got away from it. They've recently gone back.

Dr. Keller: Tissues are routinely tested, based on which tissue provides an 'official' test result as recognized by APHIS .

Dr. Detwiler: That's on the slaughter. But on the clinical cases, aren't they still asking for the brain? But even on the slaughter, they're looking only at the brainstem. We may be missing certain things if we confine ourselves to one area.

snip...

FULL TEXT;

Completely Edited Version PRION ROUNDTABLE

Accomplished this day, Wednesday, December 11, 2003, Denver, Colorado

=============================

http://madcowtesting.blogspot.com/

http://bse-atypical.blogspot.com/2010/03/atypical-bse-in-cattle-position-post.html

-------- Original Message --------

Subject: USA BIO-RADs INCONCLUSIVEs

Date: Fri, 17 Dec 2004 15:37:28 -0600 From: "Terry S. Singeltary Sr." To: susan_berg@bio-rad.com

Hello Susan and Bio-Rad,

Happy Holidays!

I wish to ask a question about Bio-Rad and USDA BSE/TSE testing and there inconclusive. IS the Bio-Rad test for BSE/TSE that complicated, or is there most likely some human error we are seeing here?

HOW can Japan have 2 positive cows with No clinical signs WB+, IHC-, HP- , BUT in the USA, these cows are considered 'negative'?

IS there more politics working here than science in the USA?

What am I missing?

-------- Original Message --------

Subject: Re: USDA: More mad cow testing will demonstrate beef's safety

Date: Fri, 17 Dec 2004 09:26:19 -0600

From: "Terry S. Singeltary Sr." snip...end

Experts doubt USDA's mad cow results

snip...END

WELL, someone did call me from Bio-Rad about this, however it was not Susan Berg. but i had to just about take a blood oath not to reveal there name. IN fact they did not want me to even mention this, but i feel it is much much to important. I have omitted any I.D. of this person, but thought I must document this ;

Bio-Rad, TSS phone conversation 12/28/04

Finally spoke with ;

Bio-Rad Laboratories 2000 Alfred Nobel Drive Hercules, CA 94547 Ph: 510-741-6720 Fax: 510-741-5630 Email: XXXXXXXXXXXXXXXXXX

at approx. 14:00 hours 12/28/04, I had a very pleasant phone conversation with XXXX XXXXX about the USDA and the inconclusive BSE testing problems they seem to keep having. X was very very cautious as to speak directly about USDA and it's policy of not using WB. X was very concerned as a Bio-Rad official of retaliation of some sort. X would only speak of what other countries do, and that i should take that as an answer. I told X I understood that it was a very loaded question and X agreed several times over and even said a political one.

my question;

Does Bio-Rad believe USDA's final determination of False positive, without WB, and considering the new atypical TSEs not showing positive with -IHC and -HP ???

ask if i was a reporter. i said no, i was with CJD Watch and that i had lost my mother to hvCJD. X did not want any of this recorded or repeated.

again, very nervous, will not answer directly about USDA for fear of retaliation, but again said X tell me what other countries are doing and finding, and that i should take it from there. "very difficult to answer"

"very political"

"very loaded question"

outside USA and Canada, they use many different confirmatory tech. in house WB, SAF, along with IHC, HP, several times etc. you should see at several talks meetings (TSE) of late Paris Dec 2, that IHC- DOES NOT MEAN IT IS NEGATIVE. again, look what the rest of the world is doing. said something about Dr. Houston stating; any screening assay, always a chance for human error. but with so many errors (i am assuming X meant inconclusive), why are there no investigations, just false positives? said something about ''just look at the sheep that tested IHC- but were positive''. ...

TSS

-------- Original Message --------

Subject: Your questions

Date: Mon, 27 Dec 2004 15:58:11 -0800

From: To: flounder@wt.net

Hi Terry:

snip...

Let me know your phone number so I can talk to you about the Bio-Rad BSE test.

Thank you

Regards

Bio-Rad Laboratories 2000 Alfred Nobel Drive Hercules, CA 94547 Ph: 510-741-6720 Fax: 510-741-5630 Email:

=================================

END...TSS

######### https://listserv.kaliv.uni-karlsruhe.de/warc/bse-l.html ##########

Wednesday, July 28, 2010

Atypical prion proteins and IBNC in cattle DEFRA project code SE1796 FOIA Final report

http://bse-atypical.blogspot.com/2010/07/atypical-prion-proteins-and-ibnc-in.html

IBNC

"All of the 15 cattle tested showed that the brains had abnormally accumulated prion protein."

Saturday, February 28, 2009

NEW RESULTS ON IDIOPATHIC BRAINSTEM NEURONAL CHROMATOLYSIS "All of the 15 cattle tested showed that the brains had abnormally accumulated PrP" 2009

SEAC 102/2

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

ATYPICAL LESION DISTRIBUTION (RBSE 92/21367)

A 6 year old, home bred (HB), Friesian x Holstein cow in a dairy herd in Aberdeenshirer submitted as a suspect BSE case in the negative study (SE0203), has been diagnosed as BSE negative on standard, statutory (obex only), diagnostic criteria at CVL.

Further examination by Dr Jeffrey at Lasswade, as required by the project design, has revealed vacuolar change in the septal nucleus and putamen which co-localised with PrP immunoreactivity. No significant lesions were found in any other part of the brain, neither was PrP found in the medulla.

It is important to note that examination of four brain blocks used earlier in the epidemic would not have detected the lesion but a 16 block study (as used in the very days of BSE) would.

FURTHER INFORMATION

The herd of origin has had 15, HB, suspect cases of BSE since July 1989 and a further case is still alive.

2. Of the 15, eight have been confirmed by standard histopathology and seven diagnosed negative (including the above case).

3. Fixed brain tissue from the negative cases exists at Lasswade (because they always collect whole brain in Scotland) but has not so far been examined further. No frozen tissue was collected so neither SAF nor PrP detection (by immunoblotting) has been attempted.

4. Mr Wells agrees with Dr Jeffrey's and Dr Simmons' findings.

FURTHER ACTION IN PROGRESS

1. The brain tissue from the negative cases will be examined in detail by conventional histopathology and ICC.

2. Kevin Taylor and his veterinary colleagues have been alerted to the situation.

OTHER RECOMMENDED ACTIONS

1. TRANSMISSION Attempt transmission from the 'case' to standard mice strains. (Note: In regard to strain typing, formalin may have modified strain phenotype - we need to discuss with NPU). Further transmission studies (eg in cattle) might be suggested if primary transmission in mice fails. These proposals have funding implications.

CODE 18-77

93/2.17/1.1

2. PrP GENOTYPING - Although only fixed brain tissue is available we are considering genotyping from parents/offspring/fixed brain. As a first step we are attempting to extract DNA from the fixed brain and to amplify the PrP gene by PCR.

3. John Wilesmith has interrogated the data base for the herd history. Other than the high proportion of negative cases nothing significant is apparent.

4. Familial relationships between suspect (including positive and negative) cases in this herd could be examined and tracings of breeding animals initiated.

5. Consideration might be given to collecting frozen spinal cord from new cases in this herd or in dispersals from it for (SAF/PrP examination).

CONCLUSIONS

1. At present it is unclear whether or not this is a singleton incident or whether the other negative cases in this herd show a similar lesion.

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

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

4. If this is a new strain all the implications need to be considered including whether or not to proceed with the further investigation of future cases negative for BSE on obex examination alone and from which whole brains are available (as in Scotland) or collected in the future. Also perhaps investigation of the tissue distribution of infectivity in these animals might be considered.

5. Animal and public health controls in place should be sufficient since all tissues (other than brain for diagnosis) are incinerated.

We observe that Dr Tyrrell would wish to be informed of this at an early opportunity and that the SEAC would wish to discuss it at their meeting in April.

R BRADLEY

M DAWSON

17 February 1993

CVO - for information and comment on further action please

cc Mr K C Taylor

Dr B J Shreeve

93/2.17/1.2

This minute is re-issued with a wider distribution.

The information contained herein should not be disseminated further except on the basis of "NEED TO KNOW".

Mr Scudamore

Mr R C Lowson

Dr D Matthews

Mr I Robertson

Dr K MacOwan

Mr C Randall

Mr J W Wilesmith

Mr G A H Wells

Dr M Jeffrey

Dr M Simmons

93/2.17/1.3

http://tna.europarchive.org/20080609145105/http://www.bseinquiry.gov.uk/files/yb/1993/02/17001001.pdf

IN CONFIDENCE

BSE - ATYPICAL LESION DISTRIBUTION (RBSE 92-21367)

http://tna.europarchive.org/20080609145105/http://www.bseinquiry.gov.uk/files/yb/1993/03/14001001.pdf

1992

NEW BRAIN DISORDER

3. WHAT ABOUT REPORTS OF NEW FORM OF BSE ?

THE VETERINARY RECORD HAS PUBLISHED AN ARTICLE ON A NEW BRAIN DISORDER OF CATTLE DISCOVERED THROUGH OUR CONTROL MEASURES FOR BSE. ALTHOUGH IT PRESENTS SIMILAR CLINICAL SIGNS TO BSE THERE ARE MAJOR DIFFERENCES IN HISTOPATHOLOGY AND INCUBATION PERIODS BETWEEN THE TWO. MUST EMPHASISE THAT THIS IS _NOT_ BSE.

4. IS THIS NEW BRAIN DISORDER A THREAT ?

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

http://collections.europarchive.org/tna/20090114131343/http://www.bseinquiry.gov.uk/files/yb/1992/10/26001001.pdf

Tuesday, November 17, 2009

SEAC NEW RESULTS ON IDIOPATHIC BRAINSTEM NEURONAL CHROMATOLYSIS (IBNC) FROM THE VETERINARY LABORATORIES AGENCY (VLA) SEAC 103/1

http://bse-atypical.blogspot.com/2009/11/seac-new-results-on-idiopathic.html

NEW RESULTS ON IDIOPATHIC BRAINSTEM NEURONAL CHROMATOLYSIS "All of the 15 cattle tested showed that the brains had abnormally accumulated PrP" 2009

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

''THE LINE TO TAKE'' ON IBNC $$$ 1995 $$$

1995

page 9 of 14 ;

30. The Committee noted that the results were unusual. the questioned whether there could be coincidental BSE infection or contamination with scrapie. Dr. Tyrell noted that the feeling of the committee was that this did not represent a new agent but it was important to be prepared to say something publicly about these findings. A suggested line to take was that these were scientifically unpublishable results but in line with the policy of openness they would be made publicly available and further work done to test their validity. Since the BSE precautions were applied to IBNC cases, human health was protected. Further investigations should be carried out on isolations from brains of IBNC cases with removal of the brain and subsequent handling under strict conditions to avoid the risk of any contamination.

31. Mr. Bradley informed the Committee that the CVO had informed the CMO about the IBNC results and the transmission from retina and he, like the Committee was satisfied that the controls already in place or proposed were adequate. ...

snip... see full text

http://collections.europarchive.org/tna/20080102204938/http://www.bseinquiry.gov.uk/files/yb/1995/06/21005001.pdf

http://web.archive.org/web/20030327015011/http://www.bseinquiry.gov.uk/files/yb/1995/06/21005001.pdf

NOW, what about the 'obex only' mode of testing used by the USDA et al for TSE, prions $$$ works for them too, a sure fire way NOT TO FIND MAD COW DISEASE $$$

NOW, read the following please, and then ask yourself, WHY the USDA et al were ONLY TESTING THE OBEX PART OF THE BRAIN in USA cattle for BSE $$$

BECAUSE they knew that would be the least likely way to find BSE/TSE in USA cattle $$$...TSS

Tuesday, November 02, 2010

IN CONFIDENCE

The information contained herein should not be disseminated further except on the basis of "NEED TO KNOW".

BSE - ATYPICAL LESION DISTRIBUTION (RBSE 92-21367) statutory (obex only) diagnostic criteria CVL 1992

http://bse-atypical.blogspot.com/2010/11/bse-atypical-lesion-distribution-rbse.html

Tuesday, July 14, 2009

U.S. Emergency Bovine Spongiform Encephalopathy Response Plan Summary and BSE Red Book Date: February 14, 2000 at 8:56 am PST

WHERE did we go wrong $$$

http://madcowtesting.blogspot.com/2009/07/us-emergency-bovine-spongiform.html

Thursday, July 14, 2011

Histopathological Studies of “CH1641-Like” Scrapie Sources Versus Classical Scrapie and BSE Transmitted to Ovine Transgenic Mice (TgOvPrP4)

http://transmissiblespongiformencephalopathy.blogspot.com/2011/07/histopathological-studies-of-ch1641.html

=========

Discussion

In the five cats in this study with a spongiform encephalopathy, fibrils were observed by electron microscopy and their major protein, Prpsc, was identified by SDS-PAGE and Western blot. The fibrils were similar to those described in sheep with scrapie (Rubenstein and others 1987, Gibson and others 1987, Scott and others 1987, Dawson and others 1987), cattle with bovine spongiform encephalopathy (Wells and others 1987, Hope and others 1988, Scott and others 1990) and humans with Creutzfeldt-Jakob disease (Merz and others 1984).

In sheep with scrapie, fibrils can be readily detected in several areas of the brain, including cerebral cortex (Stack and others 1991).

By contrast, the frequency with which fibrils were detected in cattle with BSE, DEPENDED ON THE REGION OF THE BRAIN SAMPLED; THE HIGHEST YIELD BEING OBTAINED FROM MEDULLA, MIDBRAIN, THALAMUS AND BASAL NUCLEI WHERE VACUOLA CHANGES ARE PRESENT (Scott and others 1990). This correlation between PrPsc accumulation and vacuolar pathology is also well established in laboratory animal models of scrapie (Bruce and others 1989). Because of the widespread distribution of changes in FSE (Whatt and others 1991) and the requirement, in the present study, not to compromise the histopathological examination of the brain, the frontal region of the cerebrum was therefore selected for fibril and PrPsc examinations. However, studies of the sensitivity of fibril detection in different parts of the brain in cats with FSE are required to determine whether detection can be made as readliy in other regions as in the frontal cerebral cortex.

IT IS OF INTEREST, that fibrils were detected in the brains of 3 cats (cases 9, 13, & 18) WITHOUT histopathological evidence of spongiform encephalopathy, and that in only one of them, (case 9), a Western blot for modified PrP was positive. There are precedents for the occurrence of abnormal PrP in the organs of animals incubation scrapie prior to clinical signs and/or spongiform encephalopathy...

snip...

(please see full text (and one might start downloading these documents for future use, as some disappear never to re-appear, as in some of the FDA's. ...TSS)

http://collections.europarchive.org/tna/20090113230941/http://www.bseinquiry.gov.uk/files/sc/seac12/tab04.pdf

PLEASE NOTE *

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

Subject: USDA OIG SEMIANNUAL REPORT TO CONGRESS FY 2007 1st Half (bogus BSE sampling FROM HEALTHY USDA CATTLE)

Date: June 21, 2007 at 2:49 pm PST

Owner and Corporation Plead Guilty to Defrauding Bovine Spongiform Encephalopathy (BSE) Surveillance Program

An Arizona meat processing company and its owner pled guilty in February 2007 to charges of theft of Government funds, mail fraud, and wire fraud. The owner and his company defrauded the BSE Surveillance Program when they falsified BSE Surveillance Data Collection Forms and then submitted payment requests to USDA for the services. In addition to the targeted sample population (those cattle that were more than 30 months old or had other risk factors for BSE), the owner submitted to USDA, or caused to be submitted, BSE obex (brain stem) samples from healthy USDA-inspected cattle. As a result, the owner fraudulently received approximately $390,000. Sentencing is scheduled for May 2007.

snip...

Topics that will be covered in ongoing or planned reviews under Goal 1 include:

soundness of BSE maintenance sampling (APHIS),

implementation of Performance-Based Inspection System enhancements for specified risk material (SRM) violations and improved inspection controls over SRMs (FSIS and APHIS),

snip...

The findings and recommendations from these efforts will be covered in future semiannual reports as the relevant audits and investigations are completed.

4 USDA OIG SEMIANNUAL REPORT TO CONGRESS FY 2007 1st Half

http://www.usda.gov/oig/webdocs/sarc070619.pdf

FOR IMMEDIATE RELEASE Statement May 4, 2004 Media Inquiries: 301-827-6242 Consumer Inquiries: 888-INFO-FDA

Statement on Texas Cow With Central Nervous System Symptoms

On Friday, April 30 th , the Food and Drug Administration learned that a cow with central nervous system symptoms had been killed and shipped to a processor for rendering into animal protein for use in animal feed.

FDA, which is responsible for the safety of animal feed, immediately began an investigation. On Friday and throughout the weekend, FDA investigators inspected the slaughterhouse, the rendering facility, the farm where the animal came from, and the processor that initially received the cow from the slaughterhouse.

FDA's investigation showed that the animal in question had already been rendered into "meat and bone meal" (a type of protein animal feed). Over the weekend FDA was able to track down all the implicated material. That material is being held by the firm, which is cooperating fully with FDA.

http://www.fda.gov/bbs/topics/news/2004/NEW01061.html

http://www.mail-archive.com/fda-newsdigest-l@list.nih.gov/msg00094.html

THE USDA JUNE 2004 ENHANCED BSE SURVEILLANCE PROGRAM WAS TERRIBLY FLAWED ;

CDC DR. PAUL BROWN TSE EXPERT COMMENTS 2006

In an article today for United Press International, science reporter Steve Mitchell writes:

Analysis: What that mad cow means

By STEVE MITCHELL UPI Senior Medical Correspondent

WASHINGTON, March 15 (UPI) -- The U.S. Department of Agriculture was quick to assure the public earlier this week that the third case of mad cow disease did not pose a risk to them, but what federal officials have not acknowledged is that this latest case indicates the deadly disease has been circulating in U.S. herds for at least a decade.

The second case, which was detected last year in a Texas cow and which USDA officials were reluctant to verify, was approximately 12 years old.

These two cases (the latest was detected in an Alabama cow) present a picture of the disease having been here for 10 years or so, since it is thought that cows usually contract the disease from contaminated feed they consume as calves. The concern is that humans can contract a fatal, incurable, brain-wasting illness from consuming beef products contaminated with the mad cow pathogen.

"The fact the Texas cow showed up fairly clearly implied the existence of other undetected cases," Dr. Paul Brown, former medical director of the National Institutes of Health's Laboratory for Central Nervous System Studies and an expert on mad cow-like diseases, told United Press International. "The question was, 'How many?' and we still can't answer that."

Brown, who is preparing a scientific paper based on the latest two mad cow cases to estimate the maximum number of infected cows that occurred in the United States, said he has "absolutely no confidence in USDA tests before one year ago" because of the agency's reluctance to retest the Texas cow that initially tested positive.

USDA officials finally retested the cow and confirmed it was infected seven months later, but only at the insistence of the agency's inspector general.

"Everything they did on the Texas cow makes everything they did before 2005 suspect," Brown said.

Despite this, Brown said the U.S. prevalence of mad cow, formally known as bovine spongiform encephalopathy, or BSE, did not significantly threaten human or cattle health.

"Overall, my view is BSE is highly unlikely to pose any important risk either in cattle feed or human feed," he said.

However, Jean Halloran of Consumers Union in Yonkers, N.Y., said consumers should be troubled by the USDA's secrecy and its apparent plan to dramatically cut back the number of mad cow tests it conducts.

"Consumers should be very concerned about how little we know about the USDA's surveillance program and the failure of the USDA to reveal really important details," Halloran told UPI. "Consumers have to be really concerned if they're going to cut back the program," she added.

Last year the USDA tested more than 300,000 animals for the disease, but it has proposed, even in light of a third case, scaling back the program to 40,000 tests annually.

"They seem to be, in terms of actions and policies, taking a lot more seriously the concerns of the cattle industry than the concerns of consumers," Halloran said. "It's really hard to know what it takes to get this administration to take action to protect the public."

The USDA has insisted that the safeguards of a ban on incorporating cow tissue into cattle feed (which is thought to spread the disease) and removal of the most infectious parts of cows, such as the brain and spinal cord, protect consumers. But the agency glosses over the fact that both of these systems have been revealed to be inadequately implemented.

The feed ban, which is enforced by the Food and Drug Administration, has been criticized by the Government Accountability Office in two reports, the most recent coming just last year. The GAO said the FDA's enforcement of the ban continues to have weaknesses that "undermine the nation's firewall against BSE."

USDA documents released last year showed more than 1,000 violations of the regulations requiring the removal of brains and spinal cords in at least 35 states, Puerto Rico and the Virgin Islands, with some plants being cited repeatedly for infractions. In addition, a violation of similar regulations that apply to beef exported to Japan is the reason why Japan closed its borders to U.S. beef in January six weeks after reopening them.

Other experts also question the adequacy of the USDA's surveillance system. The USDA insists the prevalence of mad cow disease is low, but the agency has provided few details of its surveillance program, making it difficult for outside experts to know if the agency's monitoring plan is sufficient.

"It's impossible to judge the adequacy of the surveillance system without having a breakdown of the tested population by age and risk status," Elizabeth Mumford, a veterinarian and BSE expert at Safe Food Solutions in Bern, Switzerland, a company that provides advice on reducing mad cow risk to industry and governments, told UPI.

"Everybody would be happier and more confident and in a sense it might be able to go away a little bit for (the USDA) if they would just publish a breakdown on the tests," Mumford added.

UPI requested detailed records about animals tested under the USDA's surveillance plan via the Freedom of Information Act in May 2004 but nearly two years later has not received any corresponding documents from the agency, despite a federal law requiring agencies to comply within 30 days. This leaves open the question of whether the USDA is withholding the information, does not have the information or is so haphazardly organized that it cannot locate it.

Mumford said the prevalence of the disease in U.S. herds is probably quite low, but there have probably been other cases that have so far gone undetected. "They're only finding a very small fraction of that low prevalence," she said.

Mumford expressed surprise at the lack of concern about the deadly disease from American consumers. "I would expect the U.S. public to be more concerned," she said.

Markus Moser, a molecular biologist and chief executive officer of Prionics, a Swiss firm that manufactures BSE test kits, told UPI one concern is that if people are infected, the mad cow pathogen could become "humanized" or more easily transmitted from person to person.

"Transmission would be much easier, through all kinds of medical procedures" and even through the blood supply, Moser said.

© Copyright 2006 United Press International, Inc. All Rights Reserved

http://www.upi.com/ConsumerHealthDaily/view.php?StoryID=20060315-055557-1284r

http://www.upi.com/Science_News/2003/12/30/Mad-Cow-Linked-to-thousands-of-CJD-cases/UPI-47861072816318/

CDC - Bovine Spongiform Encephalopathy and Variant Creutzfeldt ... Dr. Paul Brown is Senior Research Scientist in the Laboratory of Central Nervous System ... Address for correspondence: Paul Brown, Building 36, Room 4A-05, ...

http://www.cdc.gov/ncidod/eid/vol7no1/brown.htm

PAUL BROWN COMMENT TO ME ON THIS ISSUE

Tuesday, September 12, 2006 11:10 AM

"Actually, Terry, I have been critical of the USDA handling of the mad cow issue for some years, and with Linda Detwiler and others sent lengthy detailed critiques and recommendations to both the USDA and the Canadian Food Agency." ........TSS

http://madcowtesting.blogspot.com/2009/07/mad-cow-cover-up-usa-masked-as-sporadic.html

OR, what the Honorable Phyllis Fong of the OIG found ;

Audit Report Animal and Plant Health Inspection Service Bovine Spongiform Encephalopathy (BSE) Surveillance Program Â Phase II and Food Safety and Inspection Service

Controls Over BSE Sampling, Specified Risk Materials, and Advanced Meat Recovery Products - Phase III

Report No. 50601-10-KC January 2006

Finding 2 Inherent Challenges in Identifying and Testing High-Risk Cattle Still Remain

http://www.usda.gov/oig/webdocs/50601-10-KC.pdf

THIS is just ONE month report, of TWO recalls of prohibited banned MBM, which is illegal, mixed with 85% blood meal, which is still legal, but yet we know the TSE/BSE agent will transmit blood. we have this l-BSE in North America that is much more virulent and there is much concern with blood issue and l-BSE as there is with nvCJD in humans. some are even starting to be concerned with sporadic CJD and blood, and there are studies showing transmission there as well. ... this is one month recall page, where 10 MILLION POUNDS OF BANNED MAD COW FEED WENT OUT INTO COMMERCE, TO BE FED OUT. very little of the product that reaches commerce is ever returned via recall, very, very little. this was 2007, TEN YEARS AFTER THE AUGUST 4, 1997, PARTIAL AND VOLUNTARY MAD COW FEED BAN IN THE USA, that was nothing but ink on paper. i have listed the tonnage of mad cow feed that was in ALABAMA in one of the links too, this is where the infamous g-h-BSEalabama case was, a genetic relation matching the new sporadic CJD in the USA. seems this saga just keeps getting better and better.......$$$

10,000,000+ LBS. of PROHIBITED BANNED MAD COW FEED I.E. BLOOD LACED MBM IN COMMERCE USA 2007

Date: March 21, 2007 at 2:27 pm PST

RECALLS AND FIELD CORRECTIONS: VETERINARY MEDICINES -- CLASS II

___________________________________

PRODUCT

Bulk cattle feed made with recalled Darling's 85% Blood Meal, Flash Dried, Recall # V-024-2007

CODE

Cattle feed delivered between 01/12/2007 and 01/26/2007

RECALLING FIRM/MANUFACTURER

Pfeiffer, Arno, Inc, Greenbush, WI. by conversation on February 5, 2007.

Firm initiated recall is ongoing.

REASON

Blood meal used to make cattle feed was recalled because it was cross- contaminated with prohibited bovine meat and bone meal that had been manufactured on common equipment and labeling did not bear cautionary BSE statement.

VOLUME OF PRODUCT IN COMMERCE

42,090 lbs.

DISTRIBUTION

WI

___________________________________

PRODUCT

Custom dairy premix products: MNM ALL PURPOSE Pellet, HILLSIDE/CDL Prot- Buffer Meal, LEE, M.-CLOSE UP PX Pellet, HIGH DESERT/ GHC LACT Meal, TATARKA, M CUST PROT Meal, SUNRIDGE/CDL PROTEIN Blend, LOURENZO, K PVM DAIRY Meal, DOUBLE B DAIRY/GHC LAC Mineral, WEST PIONT/GHC CLOSEUP Mineral, WEST POINT/GHC LACT Meal, JENKS, J/COMPASS PROTEIN Meal, COPPINI - 8# SPECIAL DAIRY Mix, GULICK, L-LACT Meal (Bulk), TRIPLE J - PROTEIN/LACTATION, ROCK CREEK/GHC MILK Mineral, BETTENCOURT/GHC S.SIDE MK-MN, BETTENCOURT #1/GHC MILK MINR, V&C DAIRY/GHC LACT Meal, VEENSTRA, F/GHC LACT Meal, SMUTNY, A- BYPASS ML W/SMARTA, Recall # V-025-2007

CODE

The firm does not utilize a code - only shipping documentation with commodity and weights identified.

RECALLING FIRM/MANUFACTURER

Rangen, Inc, Buhl, ID, by letters on February 13 and 14, 2007. Firm initiated recall is complete.

REASON

Products manufactured from bulk feed containing blood meal that was cross contaminated with prohibited meat and bone meal and the labeling did not bear cautionary BSE statement.

VOLUME OF PRODUCT IN COMMERCE

9,997,976 lbs.

DISTRIBUTION

ID and NV

END OF ENFORCEMENT REPORT FOR MARCH 21, 2007

http://www.fda.gov/Safety/Recalls/EnforcementReports/2007/ucm120446.htm

Sunday, October 24, 2010

Australia Mad cow assessments come to a standstill, USDA hasn't a clue $

"And then FSANZ received an incomplete application from the US, which says at this stage it doesn't have the resources to provide information."

http://www.abc.net.au/rural/news/content/201010/s3044237.htm

please see full text ;

Tuesday, November 02, 2010

BSE - ATYPICAL LESION DISTRIBUTION (RBSE 92-21367) statutory (obex only) diagnostic criteria CVL 1992

http://bse-atypical.blogspot.com/2010/11/bse-atypical-lesion-distribution-rbse.html

2009 UPDATE ON ALABAMA AND TEXAS MAD COWS 2005 and 2006

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

Subject: BSE BASE MAD COW TESTING TEXAS, USA, AND CANADA, A REVIEW OF SORTS

Date: October 18, 2007 at 12:25 pm PST

BSE BASE MAD COW TESTING TEXAS, USA, AND CANADA, A REVIEW OF SORTS

HOW can they find anymore mad cows when the june 2004 enhanced bse cover-up was just that, the testing and protocol for testing was totally flawed, and proven to be so. they floundered every step of the way. and then when the atypicals started showing up, they just shut the testing down. the two suspect cows that samples sat on the shelf for 7+ months that was later confirmed, and the other suspect that sat on the shelf for 4 months, but later thought to be negative UNDER VERY QUESTIONABLE CONDITIONS, but could not have all the proper testing done on it, due to the sample being set in paraffin, which is a no no. they knew that, and that was the end around johanns and dehaven did after fong did the same to them on the 7 month delayed sample. all this done, while GW et al at the USDA were shoving down everyone throats the BSE MRR policy, the legal trading of all strains of TSE globally. ...tss

Subject: USDA BSE inconclusive MRR policy Date: August 25, 2006 at 3:52 pm PST

USDA BSE inconclusive MRR policy

BESIDES THE TEXAS MAD COW THAT WAS RENDERED AND NEVER TESTED;

FDA Statement FOR IMMEDIATE RELEASE Statement May 4, 2004 Media Inquiries: 301-827-6242 Consumer Inquiries: 888-INFO-FDA

Statement on Texas Cow With Central Nervous System Symptoms

On Friday, April 30 th , the Food and Drug Administration learned that a cow with central nervous system symptoms had been killed and shipped to a processor for rendering into animal protein for use in animal feed.

FDA, which is responsible for the safety of animal feed, immediately began an investigation. On Friday and throughout the weekend, FDA investigators inspected the slaughterhouse, the rendering facility, the farm where the animal came from, and the processor that initially received the cow from the slaughterhouse.

FDA's investigation showed that the animal in question had already been rendered into "meat and bone meal" (a type of protein animal feed). Over the weekend FDA was able to track down all the implicated material. That material is being held by the firm, which is cooperating fully with FDA.

Cattle with central nervous system symptoms are of particular interest because cattle with bovine spongiform encephalopathy or BSE, also known as "mad cow disease," can exhibit such symptoms. In this case, there is no way now to test for BSE. But even if the cow had BSE, FDA's animal feed rule would prohibit the feeding of its rendered protein to other ruminant animals (e.g., cows, goats, sheep, bison).

FDA is sending a letter to the firm summarizing its findings and informing the firm that FDA will not object to use of this material in swine feed only. If it is not used in swine feed, this material will be destroyed. Pigs have been shown not to be susceptible to BSE. If the firm agrees to use the material for swine feed only, FDA will track the material all the way through the supply chain from the processor to the farm to ensure that the feed is properly monitored and used only as feed for pigs.

To protect the U.S. against BSE, FDA works to keep certain mammalian protein out of animal feed for cattle and other ruminant animals. FDA established its animal feed rule in 1997 after the BSE epidemic in the U.K. showed that the disease spreads by feeding infected ruminant protein to cattle.

Under the current regulation, the material from this Texas cow is not allowed in feed for cattle or other ruminant animals. FDA's action specifying that the material go only into swine feed means also that it will not be fed to poultry.

FDA is committed to protecting the U.S. from BSE and collaborates closely with the U.S. Department of Agriculture on all BSE issues. The animal feed rule provides crucial protection against the spread of BSE, but it is only one of several such firewalls. FDA will soon be improving the animal feed rule, to make this strong system even stronger.

####

http://www.fda.gov/bbs/topics/news/2004/NEW01061.html

USDA orders silence on mad cow in Texas

By Steve Mitchell United Press International Published 5/11/2004 10:16 PM

WASHINGTON, May 11 (UPI) -- The U.S. Department of Agriculture has issued an order instructing its inspectors in Texas, where federal mad cow disease testing policies recently were violated, not to talk about the cattle disorder with outside parties, United Press International has learned.

The order, sent May 6 by e-mail from the USDA's Dallas district office, was issued in the wake of the April 27 case at Lone Star Beef in San Angelo, in which a cow displaying signs of a brain disorder was not tested for mad cow disease despite a federal policy to screen all such animals.

The deadly illness also is known as bovine spongiform encephalopathy.

Both the USDA and its Inspector General -- amid allegations that an offsite supervisor overruled the opinion of the inspectors onsite and made the final decision not to test the animal -- have opened up investigations to determine why agency policy was violated.

The order, which was obtained by UPI, was issued by Ijaz Qazi, circuit supervisor for the USDA's Food Safety and Inspection Service's Dallas district, which covers the entire state. It reads: "All BSE inquiries MUST be directed to Congressional Public Affairs Phone 202-720-9113 attention Rob Larew OR Steve Khon. This is an urgent message. Any question contact me. Ijaz Qazi."

Although the language might sound innocuous, experienced inspectors familiar with USDA parlance have taken to referring to the notice as a "gag order."

The National Joint Council of Food Inspection Locals -- the national inspectors union -- considers the order a violation of inspectors' free speech rights and is considering legal action against the USDA for breaching the labor agreement they have with the agency.

Inspectors alleged the order also suggests the agency is concerned about its personnel leaking damaging information about either the Texas case or the USDA's overall mad cow disease surveillance program, which has come under fire since the discovery of an infected cow in Washington state last December.

"Anytime the government suppresses an individual's freedom of speech, that's unconstitutional," Gary Dahl, president of Local 925, the Colorado inspectors union, told UPI.

Stanley Painter, chairman of the National Joint Council, said the USDA has sent out notices in the past stating inspectors cannot talk to reporters.

"It's an intimidation thing," Painter told UPI. Inspectors have the right to talk to anybody about any subject, as long as they clarify they are not speaking on behalf of the USDA and they are not doing it on government time, he said.

USDA spokesman Steven Cohen said he was not familiar with the notice from the Dallas office. He said he would look into it, but did not respond by UPI's publication time. In general, Cohen said, "There's an expectation any statement on behalf of the agency would come from the office of communications (in Washington.)"

Asked if employees could speak freely as long as they clarified that their views did not reflect those of the agency, Cohen said, "We'd rather that agency policy be communicated by those in a position to speak for the agency."

Qazi told UPI the notice was not issued in conjunction with the Texas case and it was routine agency practice that outside inquiries be referred to the Washington office. He said inspectors are free to talk to outside parties, including reporters, and he did not consider the e-mail a violation of the labor agreement with the inspectors.

Painter said the USDA's efforts to keep its employees from talking about mad cow would be better spent "with issues like protecting the consuming public instead of trying to hide things." He added he would "just about bet his last nickel" agency management was attempting to suppress information about the Texas case.

"To keep federal employees from reporting government waste, misuse of appropriations -- those types of things -- that's not a good thing either," Dahl said. "If there is something wrong, let's get it out in the open -- let's get it fixed. We're working for the public, the American consumers. I think they have the right to know this," he said.

"And believe me there's so many indicators saying that the USDA's mad cow testing program is broken," Dahl added.

At least one member of Congress, Sen. Tom Harkin, D-Iowa, agrees.

Harkin, a long-time critic of the USDA, sent a letter to Agriculture Secretary Ann Veneman on Monday, saying the Texas incident "calls into question the effectiveness and reliability of USDA's current and proposed surveillance system."

The USDA has proposed testing more than 200,000 cows -- or 10 times its current rate -- in an expanded program scheduled to begin June 1. Harkin wrote in the five-page letter, however, that given the realities of the cattle industry, it is "quite doubtful" the USDA will be able to test that many cows, particularly because it had difficulty finding 20,000 last year.

"We simply cannot tolerate a BSE testing system that fails to give valid answers to critical questions for U.S. consumers and foreign customers," Harkin said in the letter, which sharply criticizes the agency's failure to address explicitly how its new surveillance program will be implemented.

"We look forward to receiving (Harkin's) letter and having the opportunity to review it and respond to him," USDA spokesman Ed Loyd told UPI. "USDA has acknowledged there was a failure in not testing that cow in Texas for BSE, so we are all working to ensure that does not occur again."

Jim Rogers, a spokesman for USDA's Animal and Plant Health Inspection Service, which oversees the agency's mad cow surveillance program, told UPI the agency has tested about 15,500 animals since fiscal year 2004 began, on Oct. 1, 2003. However, the agency has refused to identify the states and facilities from which the cows originated. Rogers said UPI would have to seek that information through the Freedom of Information Act.

The question is central to the USDA's implementation of its expanded surveillance program. Downer cows -- those unable to stand or walk -- made up the bulk of the animals the agency tested for mad cow in previous years, but these were banned from being slaughtered for human consumption in December. This means the agency inspectors no longer can obtain brain samples from these cows at slaughterhouses as they could in the past.

Furthermore, the USDA has not provided any evidence it has worked out agreements with rendering facilities or ranchers, where downers and dead cows are now most likely to be found, to obtain the extra animals for testing.

Loyd said the agency is "working very hard to get animals on the farm that would never show up in a processing facility," and he was "not aware of any issues" that would delay the launch of the new program.

However, he was unable to provide the names or locations of the rendering facilities where the agency will be obtaining cow brains for BSE testing. He said he would look into it but did not return two follow-up phone calls from UPI before publication.

--

Steve Mitchell is UPI's Medical Correspondent. E-mail sciencemail@upi.com

Copyright © 2001-2004 United Press International

http://www.upi.com/view.cfm?StoryID=20040511-015527-4917r

Subject: The IHC Test Variables (USA BSE SURVEILLANCE) Date: June 24, 2005 at 7:59 pm PST

The IHC Test Variables:

• IHC has been the primary confirmatory test for

USDA’s BSE surveillance program and is recognized

by the World Organization for Animal Health, or OIE.

• IHC allows scientists to determine if a sample is

positive for BSE in two distinct ways:

1.) A staining technique (presence of abnormal

prion protein) that uses antibodies to detect

abnormal prion protein in the brain.

2.) A visual examination to determine whether there

are lesions (holes or "spongy" appearances)

present in the brain.

• Several variables could yield conflicting results:

o IHC is not a standardized, commercially

available test. It involves variables, including

several options in types of antibodies and other

reactive agents. The sensitivity of any given test

is influenced by those variables.

o If the level of infectivity in the animal is extremely

low, the abnormal prion in the brain will be

minimal and therefore more difficult to detect.

o Variations in the conditions under which the

staining process is performed, such as

chemicals and reactive agents used,

temperature and length of antibody exposure,

can also cause the test to yield different results.

Testing History on This Animal:

• In November 2004, a sample from this animal

returned inconclusive for BSE on a Biorad screening

test.

• The sample was subjected to an IHC confirmatory

test, which returned negative.

• USDA scientists also ran an additional, experimental

IHC "rapid" tissue fixation test for academic purposes,

which can be conducted more quickly than the IHC

confirmatory test and is therefore of interest to the

scientific community, but it has not been approved

internationally.

• While some abnormalities were noted in the

experimental IHC test results, because the test was

not a validated procedure, and because the two

approved IHC tests came back negative, the results

were not considered to be of regulatory significance

and therefore were not reported beyond the

laboratory.

• A Western blot test conducted the week of

June 5, 2005, returned positive for BSE.

• An additional IHC confirmatory test conducted the

week of June 13, 2005, by USDA scientists utilizing

different antibodies from the November 2004 test,

confirmed this case as weakly positive for BSE.

• The Veterinary Laboratories Agency in Weybridge,

England, conducted a series of diagnostic tests

including an IHC, using different antibodies from

those used by USDA in November 2004, which

returned positive results for BSE.

• Experts from the Weybridge lab confirmed the

accuracy of the results of USDA’s November

confirmatory IHC test, concurring that the case could

not have been confirmed on the basis of this sample.

• Weybridge experts also examined the November

experimental IHC test and interpreted the results to

be positive.

Potential Causes of Conflicting Results:

• USDA scientists are consulting with Weybridge

scientists to determine the cause of the conflicting

IHC test results.

• Several factors could cause or contribute to the

discrepancy as follows:

o This animal had a very low level of infectivity and

therefore the sensitivity of USDA’s routine IHC

test might not have been sufficient to detect the

disease.

o Weybridge experts indicate that deposits of

abnormal prion in the brain tissue were not

uniformly distributed and were present at low

concentration, which means that even adjacent

samples of brain tissue might not give identical

results.

Factsheet

Veterinary Services June 2005

APHIS

USDA Protocol Review:

• USDA will develop a protocol to conduct dual

confirmatory tests, the IHC and the Western blot,

when the screening test, the Biorad, returns an

inconclusive result.

• USDA and Weybridge scientists are in agreement

that the Biorad test is a very effective and appropriate

screening test.

• USDA scientists will consult with Weybridge scientists

to assess the array of antibodies available for use in

IHC confirmatory tests to determine the most

appropriate for use in United States confirmatory

tests. Those consultations will be repeated periodically.

The U.S. Department of Agriculture (USDA) prohibits discrimination

in all its programs and activities on the basis of race, color,

national origin, sex, religion, age, disability, political beliefs, sexual

orientation, or marital or family status. (Not all prohibited bases

apply to all programs.) Persons with disabilities who require alternative

means for communication of program information (Braille,

large print, audiotape, etc.) should contact USDA’s TARGET

Center at (202) 720–2600 (voice and TDD).

To file a complaint of discrimination, write USDA, Director, Office

of Civil Rights, Room 326–W, Whitten Building, 1400

Independence Avenue, SW, Washington, DC 20250–9410 or call

(202) 720–5964 (voice and TDD). USDA is an equal opportunity

provider and employer.

Safeguarding American Agriculture Animal and Plant Health Inspection Service • United States Department of Agriculture •

http://www.usda.gov/documents/vs_bse_ihctestvar.pdf

THIS confirms that the June 2004 Enhanced BSE cover-up, was just that. Like i said before, due to this terribly flawed system, those 388,000 testing to date for BSE in the USA were meaningless and should be retested. ...

Subject: USDA JOHANN'S MAD ABOUT FONG, PLANS HIS OWN LAB AND HIS OWN MAD COW ANTIBODIES ;-) Date: July 29, 2005 at 2:35 pm PST

Friday, July 29, 2005

Ames lab to take over testing for mad cow disease Published: 07/29/2005 3:52 PM

By: Associated Press - Associated Press

AMES, IA - Scientists at the National Veterinary Services Laboratories here soon will begin conducting their own Western blot tests, eliminating the need to travel to Weybridge, England, when initial rapid testing detects mad cow disease.

"I think the change is good because we're more likely to know exactly what we're dealing with on each case," said Dr. Randall Levings, director of the labs.

The change is a response to an order from U.S. Agriculture Secretary Mike Johanns.

"We took those as our marching orders," Levings said.

Mad cow disease, formally known as bovine spongiform encephalopathy, or BSE, attacks a cow's nervous system. It is characterized by spongelike holes in the brain, the result of misshapen proteins called prions that kill brain cells.

The only way it is known to spread is by cattle eating infected brain and nerve tissue from other cows. That's why the government in 1997 banned the use of cattle feed that contains remnants of other cows. Of the three cases of mad cow confirmed in the United States, all three cows were born before the feed ban, Levings said.

Since January 2004, the government has tested more than 400,000 cows for the disease, using a rapid screening test and a test known immunohistochemistry, or IHC.

Rapid testing of a sample involves removing normal proteins and adding chemicals that bind to the abnormal proteins, making them visible. The IHC test involves staining paper-thin brain tissue samples to highlight the abnormal protein.

The Western blot test, conducted at Weybridge destroys normal proteins in the brain, leaving only the abnormal prions.

In June, the nation's Office of Inspector General ordered a review of the Ames lab's testing procedures after a sample last fall tested positive in England, but negative in Ames.

A rapid test on the sample in Ames detected the presence of BSE, but the following IHC test was negative. Ames workers also relayed the results of the test, but did not complete formal paperwork.

A version of mad cow disease, known as variant Creutzfeld-Jakob, has killed about 150 people worldwide, most of them in Britain, where there was an outbreak in the 1990s.

"We're taking all of the right steps," Levings said. "It would not be a risk to human or animal health in this country. It's not high. It's very, very low."

http://www.crgazette.com/2005/07/29/Home/News/madcowtesting.htm

SO, Johann's/GW et al have perfected the BSE/TSE testing protocols and they don't need anyone else to tell them what to do. this was proven with the TEXAS mad cow cases alone, r i g h t...... $$$ IF this is the case, why is Weybridge having to confirm our inconclusives ??? this is frightening.

IF not for the Honorable Phyllis Fong, that cow would have never been proven postive, well, documented anyway, it was proven postive time and time again...

The Fong Syndrome strikes again.

GW's BSE/TSE MRR policy a recipe for disaster.

USA in dire straights.

God help us... TSS

Greetings,

"Texas Agriculture Commissioner Susan Combs suggested federal regulators wait until animals are confirmed positive or negative before disclosing results to the public."

"While markets may bounce back, enormous amounts of money can be lost in the interim,"

Combs wrote.

"In fact, during the last inconclusive announcement, it is estimated that the market dropped $25 per head on cattle, resulting in hundreds of millions of dollars in losses to our cattle industry."

Susan Combs by no means has public and consumer health at heart while she is protecting the cattle industry. She is oblivious to mad cow disease. Her soul purpose is to protect the cattle industry at all cost, including my mothers life (DOD 12/14/97), or maybe one of your family members from any strain of mad cow disease in TEXAS. SHE helped cover-up mad cow disease in TEXAS both on that inconclusive that was positive so many times it will make your head spin. PLUS, the other mad cow in TEXAS they rendered without testing at all, that came from the top out of Austin. THEY should be tried for murder. corporate homicide is what i call it. they knew for years, but kept on keeping on. IF, that positive, positive, positive, inconclusive, negative, and then 8 months later POSITIVE BY WEYBRIDGE mad cow in TEXAS would not have been made public back in November, people like myself that KNEW that cow was positive and that the USDA/COMBs et al were covering it up due to lack of proper testing, IF that news would not have been brought fourth to the public, that cow would have NEVER tested positive for mad cow disease. it was the fact that the data that was put forth in the public domain, that the public came forth and demanded that the testing be done properly and retested. THIS is what the industry and Susan Combs does not want to happen. They wish to keep it private and to manipulate the markets to there benefit, and not release the mad cow data to the public. I wrote Susan Combs on many occasions about this positive, positive, positive, incl. neg., and finally POSITIVE TEXAS MAD COW and about the one that got away, but the only thing that Susan Combs does is send me back a bought and paid for rubber stamped letter from the USDA/Industry;

----- Original Message -----

From: SusanCombs

To: Terry S. Singeltary Sr.

Sent: Monday, July 18, 2005 11:56 AM

Subject: RE: no mad cow cover up in TEXAS???

Dear Mr. Singeltary:

Thank you for contacting the Texas Department of Agriculture about the isolated case of bovine spongiform encephalopathy found in a Texas cow. I can assure you there has been no cover up by the state’s cattle industry or the U.S. Department of Agriculture, which has kept the public informed at every step in the process. First and foremost, it is important to remember that the safety procedures worked. This animal was banned from the food or feed supply, and long-standing safeguards have been in place to protect public health. Because the animal was unable to walk, it was removed from the food supply and was processed at a facility that handles animals unsuitable for human consumption. The carcass was incinerated. Texas and American cattle producers are committed to producing and ensuring a safe food product – the same safe product their families are consuming.

As far back as the late 1980s, the cattle industry began working with the U.S. government to take precautions and establish firewalls to protect public and animal health from BSE. The United States has had an active surveillance program for BSE since 1990 to test a representative sample of the adult cattle population in the United States. With the discovery of a Canadian cow in Washington state in 2003, USDA expanded the surveillance program to test hundreds of thousands of high risk animals The surveillance program is designed to specifically determine whether BSE exists in the U.S. cattle population and if so, at what level. The number of tests under the surveillance program far exceeds the level recommend by the World Animal Health Organization. With the original goal of testing 268,000 animals in a year, USDA would be able to find the disease if it occurred in as few as 1 in 10 million adult cattle with a 99 percent confidence level. Since the beginning of the program in June 2004, USDA has tested more than 400,000 animals and found only this one case, which confirms estimates that the prevalence of this disease in the U.S. cattle population is extremely low. In regards to this particular animal, the laboratory in Weybridge, England found a very low level of abnormal prion protein in the brain. In addition, the abnormalities were isolated and not consistent throughout the brain – making it possible for one sample to test negative while another sample might test positive, which was the reason for the varying results.

Our cattle producers are working hard to produce the safest beef product in the world, and their strong vigilance is a solid commitment to American consumers.

Sincerely, Susan Combs Commissioner

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

From: Terry S. Singeltary Sr. [mailto:flounder9@verizon.net]

Sent: Wednesday, July 13, 2005 12:11 PM

To: Susan Combs

Subject: no mad cow cover up in TEXAS???

Greetings Honorable Susan Combs,

no cover-up of mad cow disease in Texas ??? if not, then maybe you can explain the 7+ month delay in the announcement of the secret postive test on that postive, positive, inconclusive, negative, postive, cow that WAS going to be slaughtered for human consumption, but THEN went down and was sent to the champion pet food plant. OR maybe you can explain to me the mad cow that got away. the one MAD COW TEXAS rendered without testing at all. please explain these things to me if there is no cover up of TEXAS MAD COW disease???

thank you,

with kindest regards,

I am sincerely,

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

===================

IN TEXAS, we feed our cattle ruminant protein, and lots of it. but remember (the fda cannot seem to get this right) .1 gram is lethal; THE TEXAS GONZALES/PURINA INCIDENT SHOWED THAT 5.5 GRAMS OF RUMINANT PROTEIN WAS FED TO CATTLE ;

FOR IMMEDIATE RELEASE P01-05 January 30, 2001 Print Media: 301-827-6242 Broadcast Media: 301-827-3434 Consumer Inquiries: 888-INFO-FDA

FDA ANNOUNCES TEST RESULTS FROM TEXAS FEED LOT

Today the Food and Drug Administration announced the results of tests taken on feed used at a Texas feedlot that was suspected of containing meat and bone meal from other domestic cattle -- a violation of FDA's 1997 prohibition on using ruminant material in feed for other ruminants. Results indicate that a very low level of prohibited material was found in the feed fed to cattle.

FDA has determined that each animal could have consumed, at most and in total, five-and-one-half grams - approximately a quarter ounce -- of prohibited material. These animals weigh approximately 600 pounds.

It is important to note that the prohibited material was domestic in origin (therefore not likely to contain infected material because there is no evidence of BSE in U.S. cattle), fed at a very low level, and fed only once. The potential risk of BSE to such cattle is therefore exceedingly low, even if the feed were contaminated.

According to Dr. Bernard Schwetz, FDA's Acting Principal Deputy Commissioner, "The challenge to regulators and industry is to keep this disease out of the United States. One important defense is to prohibit the use of any ruminant animal materials in feed for other ruminant animals. Combined with other steps, like U.S. Department of Agriculture's (USDA) ban on the importation of live ruminant animals from affected countries, these steps represent a series of protections, to keep American cattle free of BSE."

Despite this negligible risk, Purina Mills, Inc., is nonetheless announcing that it is voluntarily purchasing all 1,222 of the animals held in Texas and mistakenly fed the animal feed containing the prohibited material. Therefore, meat from those animals will not enter the human food supply.

FDA believes any cattle that did not consume feed containing the prohibited material are unaffected by this incident, and should be handled in the beef supply clearance process as usual.

FDA believes that Purina Mills has behaved responsibly by first reporting the human error that resulted in the misformulation of the animal feed supplement and then by working closely with State and Federal authorities.

This episode indicates that the multi-layered safeguard system put into place is essential for protecting the food supply and that continued vigilance needs to be taken, by all concerned, to ensure these rules are followed routinely. FDA will continue working with USDA as well as State and local officials to ensure that companies and individuals comply with all laws and regulations designed to protect the U.S. food supply.

http://www.fda.gov/bbs/topics/NEWS/2001/NEW00752.html

P03.137

Transmission of BSE to Cynomolgus Macaque, a Non-human Primate; Development of Clinical Symptoms and Tissue Distribution of PrPSC

Yamakawa, Y1; Ono, F2; Tase, N3; Terao, K3; Tannno, J3; Wada, N4; Tobiume, M5; Sato, Y5; Okemoto-Nakamura, Y1; Hagiwara, K1; Sata, T5 1National Institure of Infectious diseases, Cell biology and Biochemistry, Japan; 2Corporation for Production and Research Laboratory Primates., Japan; 3National Institure of Biomedical Innovation, Tsukuba Primate Reserch Center, Japan; 4Yamauchi Univ., Veterinary Medicine, Japan; 5National Institure of Infectious diseases, Pathology, Japan

Two of three cynomolgus monkeys developed abnormal neuronal behavioral signs at 30-(#7) and 28-(#10) months after intracerebral inoculation of 200ul of 10% brain homogenates of BSE affected cattle (BSE/JP6). Around 30 months post inoculation (mpi), they developed sporadic anorexia and hyperekplexia with squeal against environmental stimulations such as light and sound. Tremor, myoclonic jerk and paralysis became conspicuous during 32 to 33-mpi, and symptoms become worsened according to the disease progression. Finally, one monkey (#7) fell into total paralysis at 36-mpi. This monkey was sacrificed at 10 days after intensive veterinary care including infusion and per oral supply of liquid food. The other monkey (#10) had to grasp the cage bars to keep an upright posture caused by the sever ataxia. This monkey was sacrificed at 35-mpi. EEG of both monkeys showed diffuse slowing. PSD characteristic for sporadic CJD was not observed in both monkeys. The result of forearm movement test showed the hypofunction that was observed at onset of clinical symptoms. Their cognitive function determined by finger maze test was maintained at the early stage of sideration. However, it was rapidly impaired followed by the disease progression. Their autopsied tissues were immunochemically investigated for the tissue distribution of PrPSc. Severe spongiform change in the brain together with heavy accumulation of PrPSc having the type 2B/4 glycoform profile confirmed successful transmission of BSE to Cynomolgus macaques. Granular and linear deposition of PrPSC was detected by IHC in the CNS of both monkeys. At cerebral cortex, PrPSC was prominently accumulated in the large plaques. Sparse accumulation of PrPSc was detected in several peripheral nerves of #7 but not in #10 monkey, upon the WB analysis. Neither #7 nor #10 monkey accumulated detectable amounts of PrPSc in their lymphatic organs such as tonsil, spleen, adrenal grands and thymus although PrPSc was barely detected in the submandibular lymph node of #7 monkey. Such confined tissue distribution of PrPSc after intracerebral infection with BSE agent is not compatible to that reported on the Cynomolgus macaques infected with BSE by oral or intra-venous (intra-peritoneal) routs, in which PrPSc was accumulated at not only CNS but also widely distributed lymphatic tissues.

P04.27

Experimental BSE Infection of Non-human Primates: Efficacy of the Oral Route

Holznagel, E1; Yutzy, B1; Deslys, J-P2; Lasmézas, C2; Pocchiari, M3; Ingrosso, L3; Bierke, P4; Schulz-Schaeffer, W5; Motzkus, D6; Hunsmann, G6; Löwer, J1 1Paul-Ehrlich-Institut, Germany; 2Commissariat à l´Energie Atomique, France; 3Instituto Superiore di Sanità, Italy; 4Swedish Institute for Infectious Disease control, Sweden; 5Georg August University, Germany; 6German Primate Center, Germany

Background: In 2001, a study was initiated in primates to assess the risk for humans to contract BSE through contaminated food. For this purpose, BSE brain was titrated in cynomolgus monkeys.

Aims: The primary objective is the determination of the minimal infectious dose (MID50) for oral exposure to BSE in a simian model, and, by in doing this, to assess the risk for humans. Secondly, we aimed at examining the course of the disease to identify possible biomarkers.

Methods: Groups with six monkeys each were orally dosed with lowering amounts of BSE brain: 16g, 5g, 0.5g, 0.05g, and 0.005g. In a second titration study, animals were intracerebrally (i.c.) dosed (50, 5, 0.5, 0.05, and 0.005 mg).

Results: In an ongoing study, a considerable number of high-dosed macaques already developed simian vCJD upon oral or intracerebral exposure or are at the onset of the clinical phase. However, there are differences in the clinical course between orally and intracerebrally infected animals that may influence the detection of biomarkers.

Conclusions: Simian vCJD can be easily triggered in cynomolgus monkeys on the oral route using less than 5 g BSE brain homogenate. The difference in the incubation period between 5 g oral and 5 mg i.c. is only 1 year (5 years versus 4 years). However, there are rapid progressors among orally dosed monkeys that develop simian vCJD as fast as intracerebrally inoculated animals.

The work referenced was performed in partial fulfilment of the study “BSE in primates“ supported by the EU (QLK1-2002-01096).

http://www.neuroprion.org/resources/pdf_docs/conferences/prion2007/abstract_book.pdf

Simian vCJD can be easily triggered in cynomolgus monkeys on the oral route using less than 5 g BSE brain homogenate.

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

WE know now, and we knew decades ago, that 5.5 grams of suspect feed in TEXAS was enough to kill 100 cows.

look at the table and you'll see that as little as 1 mg (or 0.001 gm) caused 7% (1 of 14) of the cows to come down with BSE;

Risk of oral infection with bovine spongiform encephalopathy agent in primates

Corinne Ida Lasmézas, Emmanuel Comoy, Stephen Hawkins, Christian Herzog, Franck Mouthon, Timm Konold, Frédéric Auvré, Evelyne Correia, Nathalie Lescoutra-Etchegaray, Nicole Salès, Gerald Wells, Paul Brown, Jean-Philippe Deslys

Summary

The uncertain extent of human exposure to bovine spongiform encephalopathy (BSE)--which can lead to variant Creutzfeldt-Jakob disease (vCJD)--is compounded by incomplete knowledge about the efficiency of oral infection and the magnitude of any bovine-to-human biological barrier to transmission. We therefore investigated oral transmission of BSE to non-human primates. We gave two macaques a 5 g oral dose of brain homogenate from a BSE-infected cow. One macaque developed vCJD-like neurological disease 60 months after exposure, whereas the other remained free of disease at 76 months. On the basis of these findings and data from other studies, we made a preliminary estimate of the food exposure risk for man, which provides additional assurance that existing public health measures can prevent transmission of BSE to man.

snip...

BSE bovine brain inoculum

100 g 10 g 5 g 1 g 100 mg 10 mg 1 mg 0·1 mg 0·01 mg

Primate (oral route)* 1/2 (50%)

Cattle (oral route)* 10/10 (100%) 7/9 (78%) 7/10 (70%) 3/15 (20%) 1/15 (7%) 1/15 (7%)

RIII mice (ic ip route)* 17/18 (94%) 15/17 (88%) 1/14 (7%)

PrPres biochemical detection

The comparison is made on the basis of calibration of the bovine inoculum used in our study with primates against a bovine brain inoculum with a similar PrPres concentration that was inoculated into mice and cattle.8 *Data are number of animals positive/number of animals surviving at the time of clinical onset of disease in the first positive animal (%). The accuracy of bioassays is generally judged to be about plus or minus 1 log. ic ip=intracerebral and intraperitoneal.

Table 1: Comparison of transmission rates in primates and cattle infected orally with similar BSE brain inocula

Published online January 27, 2005

http://www.thelancet.com/journal/journal.isa

It is clear that the designing scientists must also have shared Mr Bradleyâ€™s surprise at the results because all the dose levels right down to 1 gram triggered infection.

http://web.archive.org/web/20040523230128/www.bseinquiry.gov.uk/files/ws/s145d.pdf

it is clear that the designing scientists must have also shared Mr Bradleyâs surprise at the results because all the dose levels right down to 1 gram triggered infection.

http://web.archive.org/web/20030526212610/http://www.bseinquiry.gov.uk/files/ws/s147f.pdf

USDA did not test possible mad cows

By Steve Mitchell United Press International

Published 6/8/2004 9:30 PM

WASHINGTON, June 8 (UPI) -- The U.S. Department of Agriculture claims it tested 500 cows with signs of a brain disorder for mad cow disease last year, but agency documents obtained by United Press International show the agency tested only half that number.

USDA officials said the difference is made up in animals tested at state veterinary diagnostic laboratories, but these animals were not tested using the "gold standard" test employed by the agency for confirming a case of the deadly disease. Instead, the state labs used a less sensitive test that experts say could miss mad cow cases.

In addition, the state lab figures were not included in a March 2004 USDA document estimating the number of animals most likely to be infected among U.S. herds, and apparently were not given to a congressional committee that had requested agency data on the number of cows with brain disorder signs that had been tested for the disease. "This is just adding to the demise of USDA's credibility," said Felicia Nestor, senior policy adviser to the Government Accountability Project, a group in Washington, D.C., that works with federal whistleblowers. "If the USDA is going to exclude from testing the animals most likely to have the disease, that would seem to have a very negative impact on the reliability of their conclusion," Nestor told UPI.

Nestor, who has monitored the USDA's mad cow surveillance program closely for several years, asked, "Are they deliberately avoiding testing animals that look like they have the disease?" Concerns about the number of cows in U.S. herds with brain disorder symptoms have been heightened due to the recent case in Texas, in which USDA officials failed to test an animal with such symptoms, also known as central nervous system or CNS signs. This was a violation of USDA policy, which stipulates all CNS cows should be tested because they are considered the most likely to be mad cow infected.

To date, the Washington cow that tested positive last December is the only confirmed case of mad cow disease -- also known as bovine spongiform encephalopathy -- among U.S. herds. The Texas incident has alarmed the public and members of Congress because humans can contract a fatal brain disorder called variant Creutzfeldt-Jakob disease from consuming meat infected with the mad cow pathogen. If the USDA's surveillance program is allowing the riskiest cows to go untested, it raises concerns about the ability of the monitoring system to detect the disease reliably in U.S. herds, Rep. Henry Waxman, D-Calif., charged in a May 13 letter to Agriculture Secretary Ann Veneman. Dr. Peter Lurie, of the consumer group Public Citizen, said CNS cows should be the one category that absolutely has to be tested to have a sound surveillance system. "CNS animals are far and away the most important animals to test," said Lurie, who has done several analyses of the USDA's mad cow surveillance program. "If there's any category that needs 100 percent testing, that's it, because they would be the most likely place to find mad cow in America," he told UPI. "Any CNS cow that slips into the food supply represents a major case of malpractice by USDA, and similarly, the failure to test the brain of that animal to see if it was indeed infected is really a failure to protect the public." USDA officials said the agency has no estimate on how many CNS cows occur in U.S. herds.

But spokesman Ed Loyd has told UPI, and at least one other media outlet, that 500 CNS cows were tested in fiscal year 2003. Yet agency testing records for the first 10 months of FY 2003, obtained by UPI under the Freedom of Information Act, show only 254 animals that fall under the CNS category -- or about half the number Loyd cited.

After failing to respond to repeated requests from UPI for clarification of the apparent discrepancy, Loyd finally offered the explanation that an additional 45 CNS cows were tested by the USDA during the final two months of FY 2003. The remainder, he said, was made up by CNS cases tested at various state veterinary diagnostic laboratories. "We also include data reported to us from state veterinary diagnostic laboratories, and all of these are CNS cases that have been tested for BSE using a histological examination," Loyd said. "We were not using any other labs during this period, other than (the USDA lab), to run the IHC tests for BSE, which is the gold standard," he said. "This (state laboratory) information contributes important data to our surveillance effort."

However, the state labs did not use the immunohistochemistry test, which the USDA has called the "gold standard" for diagnosing mad cow disease. Instead, the labs used a different test called histopathology, which the USDA itself does not use to confirm a case, opting instead for the more sensitive IHC test. The histopathology test, unlike the IHC test, does not detect prions -- misfolded proteins that serve as a marker for infection and can be spotted early on in the course of the illness. Rather, it screens for the microscopic holes in the brain that are characteristic of advanced mad cow disease. According to the USDA's Web site, histopathology proves reliable only if the brain sample is removed soon after the death of the animal. If there is too much of a delay, the Web site states, it can be "very difficult to confirm a diagnosis by histopathology" because the brain structures may have begun to disintegrate. That is one reason the agency began using the IHC test -- it can confirm a diagnosis if the brain has begun disintegrating or been frozen for shipping.

The state labs used histopathology to screen 266 CNS cases in FY 2003, as well as 257 cases in FY 2002, according to Loyd. He did not explain why this information was not included in the testing records the agency provided to UPI and has not responded to requests for the identity of the state labs. Linda Detwiler, a former USDA veterinarian who oversaw the agency's mad cow testing program, told UPI the histopathology test probably is adequate for screening CNS cows. If they have mad cow disease, she said, it would likely be an advanced stage that should be obvious.

Other mad cow disease experts, however, said having a back-up test such as IHC would be advisable, because histopathology tests sometimes can miss evidence of infection. The Food and Agriculture Organization of the United Nations offers similar recommendations in its protocol for conducing a histopathology test. The protocol states that even if histopathology is negative, "further sampling should be undertaken" in cases "where clinical signs have strongly suggested BSE" -- a criteria that includes all of the cows tested at the state labs.

The USDA seems to agree on the need for a back-up test. Its expanded surveillance program, which began June 1, calls for using IHC -- or another test called Western blot -- to confirm any positives found on rapid tests. The March 15 document that describes the new program does not mention using histopathology to confirm cases of mad cow disease. "Subtle changes can be missed on histopathology that would probably not be as easy to miss using IHC," said Elizabeth Mumford, a veterinarian and BSE expert at Safe Food Solutions in Bern, Switzerland, a company that provides advice on reducing mad cow risk to industry and governments. "Therefore I believe it is valuable to run (histopathology)," Mumford told UPI. She noted that in Europe, two tests -- neither one the histopathology test -- are used to ensure no cases are missed. A rapid test is used initially for screening, followed by IHC as a confirmatory test.

Markus Moser, a molecular biologist and chief executive officer of the Swiss firm Prionics, which manufactures tests for detecting mad cow disease, agrees about the possibility of a case being missed by histopathology. "There were cases which were (histopathology) negative but still clearly positive with the other (testing) methods," Moser said. "BSE testing based on histology on sub-optimal tissue was probably one of the reasons why Germany was allegedly BSE-free until our test discovered that they were not" in 2000, Moser told UPI. He agreed with Detwiler that histopathology should be suitable for most cases of CNS cows, but added it still can fail to detect the disease in some CNS cases -- particularly if the sample is not optimum. "It is difficult, if not impossible, to distinguish the subtle changes in a diseased brain from artifacts like ruptures in the tissue due to tissue damage during the sampling, transport or preparation," he said.

Loyd asserted the additional CNS cases from the state labs actually yielded a total of 565 such cows the USDA had tested -- 65 more than his original figure of 500. Whether the USDA considers its total to be 500 or 565, however, either figure would exceed the agency's own estimates for the total number of such cows that it identifies annually.

According to data the USDA provided to the House Committee on Government Reform, and numbers the agency included in the March document about its expanded surveillance plan, only 201 to 249 CNS cows are identified at slaughterhouses. Approximately 129 additional cases occur on farms annually. At most, that yields a combined total of 378 CNS cows, or nearly 200 less than the 565 Loyd claims the agency tested.

The USDA surveillance plan document makes no mention of the number of CNS animals tested at state veterinary diagnostic labs. The figure also does not appear to be included in the agency's estimates of the number of high-risk animals that occur in the United States each year. The latter number was used to help the USDA calculate the number of animals it will screen for mad cow disease in its expanded surveillance plan.

USDA officials also did not include the state lab figures in response to a question from the House Committee on Government Reform, a source close to the issue told UPI. The committee, on which Waxman is the ranking Democrat, had requested in a March 8 letter to Veneman that she provide "the number of BSE tests that were conducted on cattle exhibiting central nervous system symptoms" for each of the last five years.

Loyd did not respond to a request from UPI asking why agency officials did not provide that information to the committee or include it in USDA's explanation of its expanded surveillance plan. The committee has taken note of the CNS issue and plans to delve into it further in a hearing slated for sometime in the next few months. "The committee will explore this and other issues surrounding USDA and BSE testing at a hearing later this summer," Drew Crockett, spokesman for the committee, told UPI.

-- Steve Mitchell is UPI's Medical Correspondent. E-mail sciencemail@upi.com Copyright © 2001-2004 United Press International

http://www.upi.com/view.cfm?StoryID=20040608-014607-3865r

''USDA gets a D or D minus," said Caroline Smith Dewaal of the Center for Science in the Public Interest, an advocacy group based in Washington. ''The best thing that came out of this is the work of the inspector general." It was the department's in-house watchdog, Inspector General Phyllis Fong, who skirted the USDA hierarchy by ordering retesting with a different method more than six months after a routine second-round test, known as the immunohistochemistry, or IHC, test proved negative for the disease. Agriculture Secretary Mike Johanns, who assumed office in January, has said he neither knew about nor authorized the retesting by the National Veterinary Services Laboratories in Ames, Iowa.

BESIDES the Texas mad cow that sat on the shelf for 7+ months before the Honorable Phyllis Fong of the OIG finally did the end around Johanns et al and finally had Weybridge bring that negative cow back from the dead to finally being a confirmed mad cow (hint, hint, getting MRR implemented first), was this simply another bumbling of BSE protocol, or just same old same old;

Jim Rogers (202) 690-4755 USDA Press Office (202) 720-4623 Statement by Chief Veterinary Medical Officer John Clifford Animal and Plant Health Inspection Service Regarding Non-Definitive BSE Test Results July 27, 2005

snip...

Our laboratory ran the IHC test on the sample and received non-definitive results that suggest the need for further testing. As we have previously experienced, it is possible for an IHC test to yield differing results depending on the “slice” of tissue that is tested. Therefore, scientists at our laboratory and at Weybridge will run the IHC test on additional “slices” of tissue from this animal to determine whether or not it was infected with BSE. We will announce results as soon as they are compiled, which we expect to occur by next week. I would note that the sample was taken in April, at which time the protocols allowed for a preservative to be used (protocols changed in June 2005). The sample was not submitted to us until last week, because the veterinarian set aside the sample after preserving it and simply forgot to send it in. On that point, I would like to emphasize that while that time lag is not optimal, it has no implications in terms of the risk to human health. The carcass of this animal was destroyed, therefore there is absolutely no risk to human or animal health from this animal.

snip...

http://www.aphis.usda.gov/lpa/news/2005/07/bsestatement_vs.html

Subject: Statement by Dr. John Clifford Regarding Non-Definitive BSE Test Results

Date: July 27, 2005 at 12:37 pm PST

Jim Rogers (202) 690-4755 Jerry Redding (202) 720-6959

Statement by Dr. John Clifford Regarding Non-Definitive BSE Test Results Late yesterday, we received non-definitive test results on an animal sampled as part of a voluntary extension of our enhanced BSE surveillance program. USDA is conducting further testing at the National Veterinary Services Laboratories in Ames, Iowa, in consultation with experts from the international reference laboratory in Weybridge, England.

We are also sending samples from this animal to the Weybridge laboratory for further testing. It is important to note that this animal poses no threat to our food supply because it did not enter the human food or animal feed chains.

The sample was submitted to us by a private veterinarian. As an extension of our enhanced surveillance program, accredited private veterinarians, who often visit farms in remote areas, collect samples when warranted. The sample in question today was taken from a cow that was at least 12 years of age and experienced complications during calving. The veterinarian treated the sample with a preservative, which readies it for testing using the immunohistochemistry (IHC) test - an internationally recognized confirmatory test for BSE.

Neither the rapid screening test nor the Western blot confirmatory test can be conducted on a sample that has been preserved.

Our laboratory ran the IHC test on the sample and received non-definitive results that suggest the need for further testing.

As we have previously experienced, it is possible for an IHC test to yield differing results depending on the slice of tissue that is tested. Therefore, scientists at our laboratory and at Weybridge will run the IHC test on additional slices of tissue from this animal to determine whether or not it was infected with BSE. We will announce results as soon as they are compiled, which we expect to occur by next week.

I would note that the sample was taken in April, at which time the protocols allowed for a preservative to be used (protocols changed in June 2005). The sample was not submitted to us until last week, because the veterinarian set aside the sample after preserving it and simply forgot to send it in.

On that point, I would like to emphasize that while that time lag is not optimal, it has no implications in terms of the risk to human health. The carcass of this animal was destroyed, therefore there is absolutely no risk to human or animal health from this animal. Regardless of the outcome of the further testing, I want to emphasize that human and animal health in the United States are protected by a system of interlocking safeguards.

The most important of these is the ban on specified risk materials from the food supply and the Food and Drug Administrations feed ban. And by any measure, the incidence of BSE in this country is extremely low.

snip...update 2011

Thursday, July 14, 2011

Valley Farm Meats (DBA Strasburg Provision, Inc) Issues Precautionary Recall for Beef Products Due to Possible Contamination with Prohibited Materials SRM

Ohio Department of Agriculture and Ohio Department of Health

http://transmissiblespongiformencephalopathy.blogspot.com/2011/07/valley-farm-meats-dba-strasburg.html

snip...continued ;

Our enhanced surveillance program is designed to provide information about the level of prevalence of BSE in the United States. We are extremely gratified that to date, all sectors of the cattle industry have cooperated in this program by submitting samples from more than 419,000 animals from the highest risk populations. To date, only one animal has tested positive for the disease as part of the surveillance program. These interlocking safeguards continue to protect our food supply.

# Note to Reporters: USDA news releases, program announcements and media advisories are available on the Internet. Go to the APHIS home page at http://www.aphis.usda.gov and click on the News button. Also, anyone with an e-mail address can sign up to receive APHIS press releases automatically. Send an e-mail message to lyris@mdrdlyriss10.aphis.usda.gov and leave the subject blank. In the message, type subscribe press_releases. USDA News oc.news@usda.gov 202 720-4623

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

"The sample was submitted to us by a private veterinarian. As an extension of our enhanced surveillance program, accredited private veterinarians who often visit farms in remote areas collect samples when warranted. The sample in question today was taken from a cow that was at least 12 years of age and experienced complications during calving. "The veterinarian treated the sample with a preservative which readies it for testing using the immunohistochemistry test, an internationally recognized confirmatory test for BSE. "Neither the rapid screening test nor the Western blot confirmatory test can be conducted on a sample that has been preserved. Our laboratory ran the IHC test on the sample and received non-definitive results that suggest the need for further testing. "As we have previously experienced, it is possible for an IHC test to yield differing results, depending on the slice of tissue that is tested. Therefore scientists at our laboratory and at Weybridge will run the IHC test on additional slices of tissue from this animal to determine whether or not it was infected with BSE. "We will announce results as soon as they are compiled, which we expect to occur by next week.

snip...

http://www.usda.gov/wps/portal/usdahome?contentidonly=true&contentid=2005/07/0280.xml

In Reply to:

Re: Statement by Dr. John Clifford Regarding Non-Definitive BSE Test Results posted by TSS on July 27, 2005 at 12:53 pm:

o.k., let me get this right. i am pondering here;-) all the time this TEXAS positive, positive, (secret) positive, inconclusive, negative, then Weybridge confirmed 2nd BSE documented case (thanks to the Honorable Phyllis Fong), all this time this BSe going on in TEXAS, was plastered all over the news, this guy forgot about that sample, and it just sat up on some shelf wasting away for months, as to be in such bad shape, they now cannot even test it properly. r i g h t ... like ooops, sorry. ...end

============================================

The animal died in April, but the veterinarian forgot to send the sample to USDA until this month, Mr. Clifford said. "While that time lag is not optimal, it has no implications in terms of the risk to human health," he said. IHC tests returned conflicting results on the Texas cow. Use of the preservative means that the other tests commonly done when mad cow is suspected, initial rapid screening and Western blot, can't be performed on this sample, the official said. Mr. Clifford said it's possible to get different results, "depending on the slice of tissue that is tested." The fatal brain-wasting disease is known medically as bovine spongiform encephalopathy, or BSE. In people, eating tainted meat products has been linked to about 150 deaths from a fatal disorder called variant Creutzfeldt-Jakob disease. Most of the deaths were in the United Kingdom, where there was an outbreak in the 1980s and 1990s. The U.S. banned Canadian cattle in May 2003 following Canada's first case of mad-cow disease. The U.S. was about to lift the ban in March when U.S. District Judge Richard Cebull in Billings, Mont., granted an injunction to a ranchers' group called R-CALF United Stockgrowers of America. The ranchers had sued to keep the border closed to Canadian cattle, saying the disease presented a risk to the U.S. beef industry as well as to American consumers. The 9th U.S. Circuit Court of Appeals reversed the injunction earlier this month, allowing cattle shipments from Canada to resume. The lifting of the ban reopens the U.S. to cattle younger than 30 months and expands the list of beef products Canada is allowed to ship to the U.S. Older animals are still banned, because infection levels are believed to increase with age.

Copyright © 2005 Associated Press

http://online.wsj.com/

Greetings, this is what you call the 'FONG' syndrome. make sure she can't make them do a WB on this sample. I BEG THE OIG and the Honorable Phyllis Fong to investigate this blunder too. there is no way that sample sat on a shelf while the world waited on that Texas mad cow blunder dust to settle, and someone just forgets about it. i just don't believe this either...

============================================

From: TSS Subject:

Re: Statement by Dr. John Clifford Regarding Non-Definitive BSE Test Results

Date: July 27, 2005 at 12:53 pm PST

In Reply to:

Statement by Dr. John Clifford Regarding Non-Definitive BSE Test Results posted by TSS on July 27, 2005 at 12:37 pm:

----- Original Message -----

From: "Terry S. Singeltary Sr."

To:

Sent: Wednesday, July 27, 2005 2:57 PM

Subject: Re: Statement by Dr. John Clifford Regarding Non-Definitive BSE Test Results

##################### Bovine Spongiform Encephalopathy #####################

Greetings,

with great disgust i must comment on this BSE/USDA/APHIS blunder as well. i swear, larry curly and mo could do a better job at this than is being done right now. for this reason alone the USA BSE GBR risk assessment should be raised immediately to BSE GBR IV; "I would note that the sample was taken in April, at which time the protocols allowed for a preservative to be used (protocols changed in June 2005). The sample was not submitted to us until last week, because the veterinarian set aside the sample after preserving it and simply forgot to send it in. On that point, I would like to emphasize that while that time lag is not optimal, it has no implications in terms of the risk to human health. The carcass of this animal was destroyed, therefore there is absolutely no risk to human or animal health from this animal."

for Heavens sake, this is July 27, 2005 and we are just now getting this sample to Weybridge. this reeks !

THEN, to think of GWs BSE MRR policy of trading TSEs of all strains globally. again, USA and North America's BSE GBR should be raised to BSE GBR IV immediately. still very disgusted in bacliff, texas...TSS

Faults in USDA testing cited Mad cow case in Texas showed glaring missteps

By Barry Shlachter, Knight Ridder | August 7, 2005

snip...

What Fong and the public were unaware of was that Ames researchers had also used an experimental rapid version of the IHC test on brain tissue from the Texas cow. That proved positive for the disease, but staff members thought the result was technically flawed. The USDA did not disclose until just recently that the Ames lab had conducted the experimental test.

snip...

Months later, Fong stepped in and ordered more tests. A ''Western blot" test proved positive, as did later tests at a lab in Weybridge, England. Finally in June, two days after the Weybridge lab confirmed the mad cow case, a chastened USDA announced that in addition to the routine IHC test, it was adopting the Western blot procedure whenever an initial ''BioRad" screening test indicates mad cow disease is possible. In addition, backup tests will now be conducted at Britain's national veterinary laboratory in Weybridge when earlier test results conflict or are inconclusive.

http://www.boston.com/news/nation/articles/2005/08/07/faults_in_usda_testing_cited/

NOW, all the above announced July 27, 2005. SO, the other 'inconclusive' sample has been sitting on the shelf since April, some 4 months earlier, give or take a few days. NOW, what has been going on while this other inconclusive BSE/BASE mad cow sits on the shelf.

Lets look at that BSE MRR COMMODITY time frame ;-)

7/20/05 USDA, APHIS, Veterinary Services, National Center for Import and Export: Protocol for The Importation of Farm Raised Cervids from Canada PDF USDA, APHIS, Veterinary Services, National Center for Import and Export: Protocol for The Importation of Camelids from Canada PDF

7/15/05 Importation of Bovines (Cattle or Bison) from Canada for Feeding PDF BSE Minimal-Risk Regions and the Importation of Live Animals Importers, Brokers, and Other Interested Parties PDF BSE Minimal-Risk Regions and the Importation of Live Animals Accredited Veterinarians or Other Interested Parties PDF USDA, APHIS, Veterinary Services, National Center for Import and Export: Protocol for The Importation of Cattle or Bison for Feeding from Canada PDF USDA, APHIS, Veterinary Services, National Center for Import and Export: Protocol for the Importation of Cattle, Bison, Sheep and Goats for Immediate Slaughter from Canada PDF USDA, APHIS, Veterinary Services, National Center for Import and Export: Protocol for the Importation of Sheep and Goats for Feeding from Canada PDF Animal Products Implementation: Bovine Spongiform Encephalopathy; Minimal-Risk Regions and Importation of Commodities from Canada PDF Johanns Announces Next Steps for Importing Canadian Cattle Transcript of Tele-News Conference with Agriculture Secretary Mike Johanns Bovine Spongiform Encephalopathy; Minimal-Risk Regions and Importation of Commodities— FINAL RULE— 9 CFR Parts 93, 94, 95, and 96 [Docket No. 03-080-3] Bovine Spongiform Encephalopathy; Minimal-Risk Regions and Importation of Commodities; Partial Delay of Applicability [Docket No. 03-080-6] — Final rule; partial delay of applicability — 9 CFR Parts 94 and 95 Published March 11, 2005 — 70 FR 12112-12113 Text | PDF • Risk Document PDF • Economic Analysis PDF • Appendices to economic analysis PDF • Final environmental assessment PDF • Final Rule on BSE and Minimal-Risk Regions (Factsheet) • Questions and Answers for Minimal Risk/Canada Rule • Port of Entry for Eligible Ruminants

7/14/05 Secretary Johanns Statement on Ninth Circuit Court Ruling

04/01/05 Canada, Mexico And United States Release Harmonized North American BSE Strategy Harmonization of a BSE Strategy (PDF)

03/17/05 U.S. Government Requests Appeal In Minimal-Risk Rule Case

03/04/05 BSE Minimal-Risk Regions and Importation of Live Animals and Commodities From Canada Delay of Effective Date (Memo)

03/03/05 Statement By Agriculture Secretary Mike Johanns Regarding The Temporary Injunction Issued By The U.S. District Court For The District Of Montana Regarding USDA's Minimal-Risk Rule NOT to forget ; It should be noted that since the enhanced surveillance program began, USDA has also conducted approximately 9,200 routine IHC tests on samples that did not first undergo rapid testing. This was done to ensure that samples inappropriate for the rapid screen test were still tested, and also to monitor and improve upon IHC testing protocols. Of those 9,200 routine tests, one test returned a non-definitive result on July 27, 2005. That sample underwent additional testing at NVSL, as well as at the Veterinary Laboratories Agency in Weybridge, England, and results were negative. ......

http://www.aphis.usda.gov/lpa/issues/bse_testing/test_results.html

r i g h t ............

By Steve Mitchell United Press International Published 2/9/2004 7:06 PM

WASHINGTON, Feb. 9 (UPI) -- The federal laboratory in Ames, Iowa, that conducts all of the nation's tests for mad cow disease has a history of producing ambiguous and conflicting results -- to the point where many federal meat inspectors have lost confidence in it, Department of Agriculture veterinarians and a deer rancher told United Press International. The veterinarians also claim the facility -- part of the USDA and known as the National Veterinary Services Laboratories -- has refused to release testing results to them and has been so secretive some suspect it is covering up additional mad cow cases. ...

http://www.upi.com/view.cfm?StoryID=20040209-061848-3665r

-------- Original Message --------

Subject: re-USDA's surveillance plan for BSE aka mad cow disease

Date: Mon, 02 May 2005 16:59:07 -0500

From: "Terry S. Singeltary Sr."

To: paffairs@oig.hhs.gov, HHSTips@oig.hhs.gov, contactOIG@hhsc.state.tx.us

Greetings Honorable Paul Feeney, Keith Arnold, and William Busby et al at OIG, ...............

snip...

There will be several more emails of my research to follow. I respectfully request a full inquiry into the cover-up of TSEs in the United States of America over the past 30 years. I would be happy to testify...

Thank you,

I am sincerely,

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

Date: June 14, 2005 at 1:46 pm PST

In Reply to: Re: Transcript Ag. Secretary Mike Johanns and Dr. John Clifford, Regarding further analysis of BSE Inconclusive Test Results posted by TSS on June 13, 2005 at 7:33 pm:

Secretary of Agriculture Ann M. Veneman resigns Nov 15 2004, three days later inclusive Mad Cow is announced.

June 7th 2005 Bill Hawks Under Secretary for Marketing and Regulatory Programs resigns.

Three days later same mad cow found in November turns out to be positive. Both resignation are unexpected.

just pondering...

TSS

-------- Original Message --------

Subject: Re: BSE 'INCONCLUSIVE' COW from TEXAS ???

Date: Mon, 22 Nov 2004 17:12:15 -0600

From: "Terry S. Singeltary Sr."

To: Carla Everett References: log in to unmask]> <[log in to unmask]

Greetings Carla,still hear a rumor;

Texas single beef cow not born in Canada no beef entered the food chain?

and i see the TEXAS department of animal health is ramping up forsomething, but they forgot a url for update?

I HAVE NO ACTUAL CONFIRMATION YET...

can you confirm???

terry

==============================

-------- Original Message --------

Subject: Re: BSE 'INCONCLUSIVE' COW from TEXAS ???

Date: Fri, 19 Nov 2004 11:38:21 -0600 From: Carla Everett

To: "Terry S. Singeltary Sr." References: log in to unmask]

The USDA has made a statement, and we are referring all callers to the USDA web site. We have no informationabout the animal being in Texas. Carla

At 09:44 AM 11/19/2004, you wrote:

Greetings Carla, i am getting unsubstantiated claims of this BSE 'inconclusive' cow is from TEXAS. can you comment on this either way please? thank you, Terry S. Singeltary Sr.

===================

-------- Original Message --------

Subject: Re: BSE 'INCONCLUSIVE' COW from TEXAS ???

Date: Mon, 22 Nov 2004 18:33:20 -0600

From: Carla Everett

To: "Terry S. Singeltary Sr." References: [log in to unmask] [log in to unmask] [log in to unmask] [log in to unmask] [log in to unmask];

our computer department was working on a place holder we could post USDA's announcement of any results. There are no results to be announced tonight by NVSL, so we are back in a waiting mode and will post the USDA announcement when we hear something.

At 06:05 PM 11/22/2004,

you wrote:

why was the announcement on your TAHC site removed?

Bovine Spongiform Encephalopathy:

November 22: Press Release title here

star image More BSE information

terry

Carla Everett wrote:

no confirmation on the U.S.'inconclusive test...

no confirmation on location of animal.

==========================

UPI Exclusive: No mad cow tests in Wash.

By Steve Mitchell United Press International Published 1/15/2004 2:46 PM

WASHINGTON, Jan. 15 (UPI) -- Federal agriculture officials did not test any commercial cattle for mad cow disease through the first seven months of 2003 in Washington state -- where the first U.S. case of the disease was detected last month -- according to records obtained by United Press International.

The U.S. Department of Agriculture's records of mad cow screenings, conducted on 35,000 animals between 2001 to 2003, also reveal no animals were tested for the past two years at Vern's Moses Lake Meats, the Washington slaughterhouse where the mad cow case was first detected.

In addition, no mad cow tests were conducted during the two-year period at any of the six federally registered slaughterhouses in Washington state. This includes Washington's biggest slaughterhouse, Washington Beef in Toppeni$h -- the 17th largest in the country, which slaughters 290,000 head per year -- and two facilities in Pasco that belong to Tyson, the largest beef slaughtering company in the United States.

In 2002, nearly every test conducted in Washington was on animals from Midway Meats in Centralia, the packing plant where Vern's Moses sent the infected cow carcass. The meat was distributed to several states where some people apparently consumed it, raising concerns about the possibility of contracting the human equivalent of mad cow, an always fatal, brain-wasting condition known as variant Creutzfeldt-Jakob disease. ...

http://www.upi.com/view.cfm?StoryID=20040114-041124-1470r

USDA 2003

We have to be careful that we don't get so set in the way we do things that we forget to look for different emerging variations of disease. We've gotten away from collecting the whole brain in our systems. We're using the brain stem and we're looking in only one area. In Norway, they were doing a project and looking at cases of Scrapie, and they found this where they did not find lesions or PRP in the area of the obex. They found it in the cerebellum and the cerebrum. It's a good lesson for us. Ames had to go back and change the procedure for looking at Scrapie samples. In the USDA, we had routinely looked at all the sections of the brain, and then we got away from it. They've recently gone back. Dr. Keller: Tissues are routinely tested, based on which tissue provides an 'official' test result as recognized by APHIS .

Dr. Detwiler: That's on the slaughter. But on the clinical cases, aren't they still asking for the brain? But even on the slaughter, they're looking only at the brainstem. We may be missing certain things if we confine ourselves to one area.

snip.............

Dr. Detwiler: It seems a good idea, but I'm not aware of it. Another important thing to get across to the public is that the negatives do not guarantee absence of infectivity. The animal could be early in the disease and the incubation period. Even sample collection is so important. If you're not collecting the right area of the brain in sheep, or if collecting lymphoreticular tissue, and you don't get a good biopsy, you could miss the area with the PRP in it and come up with a negative test. There's a new, unusual form of Scrapie that's been detected in Norway. We have to be careful that we don't get so set in the way we do things that we forget to look for different emerging variations of disease. We've gotten away from collecting the whole brain in our systems. We're using the brain stem and we're looking in only one area. In Norway, they were doing a project and looking at cases of Scrapie, and they found this where they did not find lesions or PRP in the area of the obex. They found it in the cerebellum and the cerebrum. It's a good lesson for us. Ames had to go back and change the procedure for looking at Scrapie samples. In the USDA, we had routinely looked at all the sections of the brain, and then we got away from it. They've recently gone back.

Dr. Keller: Tissues are routinely tested, based on which tissue provides an 'official' test result as recognized by APHIS .

Dr. Detwiler: That's on the slaughter. But on the clinical cases, aren't they still asking for the brain? But even on the slaughter, they're looking only at the brainstem. We may be missing certain things if we confine ourselves to one area.

snip...

FULL TEXT;

Completely Edited Version PRION ROUNDTABLE

Accomplished this day, Wednesday, December 11, 2003, Denver, Colorado

Subject: Canada’s Protocols for BSE Surveillance DOES NOT MANDATE WB CONFIRMATION Date: August 4, 2005 at 1:16 pm PST

Canadian Food Inspection Agency Factsheet

Canada’s Protocols for BSE Surveillance Printer-Friendly PDF version

BSE testing in Canada is in full accordance with the guidelines recommended by the World Organisation for Animal Health (OIE).

The samples collected target the highest risk cattle. This includes animals over 30 months of age that are dead, down, dying or diseased. In addition, any cattle that are exhibiting symptoms consistent with BSE must be reported to the Canadian Food Inspection Agency. This targeted surveillance program is crucial to defining the level of BSE in Canada and to confirming the effectiveness of the measures in place to protect human and animal health from the disease. A robust surveillance program, with strong producer participation, gives domestic and international consumers confidence that Canada is taking responsible actions to monitor the health of the national herd.

In June 2005, Canada exceeded its minimum testing target of 30,000 animals for the year and, as of August 1, more than 36,000 cattle had been tested. The Government of Canada continues to work with provincial governments to support and encourage the participation of Canadian cattle producers in the surveillance program.

Preliminary Testing Procedures In Canada, two rapid BSE screening tests are used for routine surveillance - the Prionics®- Check Western and the Bio-Rad TeSeE®.

Evaluations conducted by the CFIA and agencies in other governments have found the tests to be 100% accurate for detecting BSE in cattle in later stages of the incubation period. Due to the high sensitivity of the tests, there are rare instances in which samples not infected with BSE may produce an initial reaction, thus necessitating re-testing.

Second Round of Testing Initially reactive samples are referred to as “non-negatives”and require that the same test be repeated in duplicate by the screening laboratory.

If the repeat tests are reactive, the sample is considered “inconclusive” for BSE, and the tissue from the animal is forwarded to the National BSE Reference Laboratory, National Centre for Foreign Animal Disease (NCFAD) in Winnipeg for confirmatory testing.

The rapid test on an inconclusive sample is repeated at the National BSE Reference Laboratory and if the test is again reactive, the sample is considered to be a BSE “suspect” and is subject to confirmatory testing. Even if this third rapid test is negative, a confirmatory test (immunohistochemistry or OIE Western Blot) is run for quality assurance purposes.

Confirmatory Testing The immunohistochemistry (IHC) and the OIE Western Blot, also called the SAF Immunoblot, are internationally recognized confirmatory tests for BSE. The IHC is the principle confirmatory test used at NCFAD.

The OIE Western Blot test may be performed on the sample in addition to, or as an alternative to, the IHC test. It is always used on poor quality tissue samples when it may not be possible to conduct the IHC test, or on suspect samples where the IHC is negative.

http://www.inspection.gc.ca/english/anima/heasan/disemala/bseesb/bseesbsurve.shtml

THIS protocol has a flaw, the word ''or'' should be changed to ''and'';

(immunohistochemistry or OIE Western Blot)

should read ;

(immunohistochemistry AND OIE Western Blot)

WHY ASK for the blunders and the risks by not using WB, as been documented by the USDA et al in the USA???

WHY even go there???

IF the WB picks up detection where the IHC does not, then why are we even discussing this, IF they were truly trying to find and eradicate BSE/TSE$$$

IHC AND WB should be used for confirmation of any inconclusive.

anything less is not a confirmation, it's a guess.

still disgusted in Sunny Bacliff, Texas USA...TSS

Subject: Re: Canada’s Protocols for BSE Surveillance DOES NOT MANDATE WB CONFIRMATION

Date: August 6, 2005 at 10:05 am PST

In Reply to: Canada’s Protocols for BSE Surveillance DOES NOT MANDATE WB CONFIRMATION

posted by TSS on August 4, 2005 at 1:16 pm:

##################### Bovine Spongiform Encephalopathy #####################

Hello Karin,

indeed i did read the last line, i just think any confusion should be eliminated. i think with the word 'or' is just asking for trouble. one persons opinion on a 'poor quality' tissue sample, may not be the same as the next persons opinion. so why even have the potential for confusion there? i am sure you are aware of this, but maybe some other newer members on the list have not read this study;

Effect of Tissue Deterioration on Postmortem BSE Diagnosis by Immunobiochemical Detection of an Abnormal Isoform of Prion Protein

Hiroko HAYASHI1), Masuhiro TAKATA1), Yoshifumi IWAMARU1), Yuko USHIKI1)2), Kumiko M. KIMURA1), Yuichi TAGAWA1), Morikazu SHINAGAWA1) and Takashi YOKOYAMA1)

1) Prion Disease Research Center, National Institute of Animal Health 2) Nippi Research Institute of Biomatrix (Received 25-Aug-2003) (Accepted 14-Jan-2004)

ABSTRACT.

Surveillance for bovine spongiform encephalopathy (BSE) in fallen stock in Japan is conducted with a commercial enzyme-linked immunosorbent assay (ELISA) for mass screening, with Western blotting (WB) and immunohistochemistry performed for confirmation of the ELISA. All tests are based on immunological detection of an abnormal isoform of the prion protein (PrPSc) in brain tissues, which have sometimes deteriorated by the time samples from fallen stock reach a diagnostic laboratory. To evaluate BSE surveillance procedures for fallen stock, we examined PrPSc detection from artificially deteriorated BSE-affected bovine brain tissues with a commercial ELISA kit and compared the results with those of WB. The optical density (OD) values of the ELISA decreased with advancing deterioration of the tissues, whereas no reduction in the signal for PrPSc was observed in WB, even when performed after 4 days of incubation at 37°C. The progressive decrease in the OD values in the ELISA appear to be caused by a partial loss of the N-terminal moiety of PrPSc due to digestion by endogeneous and/or contaminated microbial enzymes, and by the presence of ELISA inhibitors that are generated in deteriorated tissues. These results suggest that WB is the most reliable test for fallen stock, especially for cattle brains within decaying carcasses. KEY WORDS: BSE, ELISA, PrPSc, Western blot

[PDF (96K)] [References]

To cite this article: Hiroko HAYASHI, Masuhiro TAKATA, Yoshifumi IWAMARU, Yuko USHIKI, Kumiko M. KIMURA, Yuichi TAGAWA, Morikazu SHINAGAWA and Takashi YOKOYAMA “Effect of Tissue Deterioration on Postmortem BSE Diagnosis by Immunobiochemical Detection of an Abnormal Isoform of Prion Protein”. J. Vet. Med. Sci.. Vol. 66: 515-520. (2004) .

http://www.jstage.jst.go.jp/article/jvms/66/5/66_515/_article

FULL TEXT PDF;

Another problem in testing fallen stock for BSE may arise from unequal distribution of PrPSc in BSE-affected brains. Spongiform changes and accumulation of PrPSc are most frequently observed in the obex region [15, 18], but, it could be quite difficult to collect the obex region precisely from extensively deteriorated and liquefied brain tissue. Furthermore, in such cases it would be difficult to perform IHC as a confirmation test.

It has been shown that sample autolysis does not affect detection of PrPSc by means of WB [3, 5, 13]. Our WB results also demonstrated no reduction in the PrPSc signal as a result of deterioration at 30*C or 37*C for up to 4 days, as so far examined (Figs. 2A and 3A). In this study, we showed that several problems undermine the utility of the ELISA with deteriorated samples, whereas WB remains very dependable. Therefore, WB might be the only reliable procedure to detect PrPSc in severely damaged samples from fallen stock...

FULL TEXT 6 PAGES;

http://www.jstage.jst.go.jp/article/jvms/66/5/515/_pdf

Karin writes;

I would be more worried about the latest USA suspect where no WB can be done, due to formalin fixation of the sample. I don’t know if the “reference” laboratory in Weybridge has ever missed any BSE-positive cattle (or atypical bovine TSEs), but they have certainly failed to confirm several cases of atypical scrapie, because they insisted on using the so-called validated methods recommended by the OIE before 2003. I hope they now have solved this problem.

===

i agree with this. in fact, the OIE since adhering to GWs BSE MRR policy (minimal risk region), and doing away with the USA, Canada, and Mexico BSE GBR Risk assessments, was anything but 'sound science'. by the OIE adhering to this 'junk science' of this administrations corporate scientists, the OIE has done nothing more than become a commodity brokerage for the legal trading of all phenotypes of TSEs Globally. THEY have in essence done away with 30 years of trying to eradicate TSEs globally. MILLIONS and millions of dollars down the drain, with MILLIONS and millions of humans and animals now becoming exposed even more than before, due to nothing more than greed and the almighty buck. as GW says, ''bring em on''. he will get exactly what he asks for again in the years and decades to come. but, as my birthday card today states;

This birthday you have something to be thankful for (with a picture of GW on the front), I CAN'T RUN AGAIN....................amen!

SO why should he care, he will not be in office, but the markets will be o.k. for now, borders open, and the list of demented and dead will continue to slowly grow even more, with more strains of TSE mutating and being exported throughout the globe... gee thanks GW/OIE!

==============================================

5.1.3. National TSE Veterinary Diagnostic Laboratory Network

The CFIA created a National TSE Veterinary Diagnostic Laboratory Network in 2001 to ensure consistency of diagnostic testing nationally. The network includes CFIA TSE reference laboratories, CFIA and provincial network laboratories. Standard operating procedures (Appendix 4), control material and panels are provided by the federal laboratories as part of a Quality Assurance Program. Training and research are also provided. Quality assurance and biosafety guidelines were distributed early in 2002.

5.2. Diagnostic Tests

All samples are tested by histopathology (H&E) and some are tested by IHC (see Appendix 4 for test standard operating procedures). According to the OIE Manual of Standards (OIE, 2000), surveillance for BSE requires laboratory examination of brain from clinically suspect animals by histopathology and, if necessary, other methods described in the manual (i.e. western blot, scrapie-associated-fibril examination and detection of abnormal PrP by immunohistochemistry).

Prior to the opening of the NCFAD laboratory (1997), testing for BSE was performed at the ADRI, Ottawa. At this laboratory, the validation of IHC using a polyclonal antibody on central nervous tissue began in 1994 and was completed in 1995. Validation of the IHC test for BSE using a monoclonal antibody was carried out at the National BSE Reference Laboratory at NCFAD/CFIA in Winnipeg in 2001 (Czub 2002).

As of January 2002, the provinces of Alberta, Ontario and Saskatchewan have introduced IHC testing in their laboratories. The province of Manitoba has the option to send samples to Saskatchewan for IHC, and the province of Quebec is currently acquiring laboratory capability for IHC testing (Greenwood 2002). To ensure consistency of diagnostic testing across all laboratories, the CFIA initiated a National TSE Veterinary Diagnostic Laboratory Network in 2001 (see Section 5.1.3 for details).

While less than half of Canada’s BSE surveillance samples have historically been tested by IHC (see Table 2), by the end of 2002 more than 90% of all BSE samples will be tested by this method.

Confirmatory testing of a BSE suspect sample is carried out at the National BSE Reference Laboratory at NCFAD/CFIA in Winnipeg.

Rapid Tests:

Rapid tests for BSE diagnosis are not currently used in Canada; however, the CFIA is evaluating certain rapid tests used in Europe. Once the technology has been obtained and standardized in the National BSE Reference Laboratory in Winnipeg, the CFIA will consider application of these tests in the Canadian BSE Surveillance Program.

2In some countries, the terminology “fallen stock” is used for animals described herein as “non-ambulatory” or “animals found dead.”

3Total Cow Population 5,574,000 (dairy cows 1,122,400, beef cows 4,451,600) Source: 1996 Agricultural Census.

http://www.inspection.gc.ca/english/sci/ahra/bseris/bserisb1e.shtml

----- Original Message -----

From: Terry S. Singeltary Sr.

To: Debra.Beasley@aphis.usda.gov

Sent: Tuesday, November 24, 2009 11:01 AM

Subject: OIE has recently published its proposed animal welfare guidelines for public comment

Greetings USDA/APHIS et al,

I would kindly like to comment on OIE proposed guidelines.

AS I said before, OIE should hang up there jock strap now, since it appears they will buckle every time a country makes some political hay about trade protocol, commodities and futures. IF they are not going to be science based, they should do everyone a favor and dissolve there organization. THE reason most every country around the globe came down with BSE/TSE in their cattle, were due to the failed and flawed BSE/TSE testing and surveillance policy of the O.I.E. NOW, they don't even acknowledge atypical scrapie it seems, as one for concern $

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

Tuesday, May 24, 2011 2:24 PM

O.I.E. Terrestrial Animal Health Standards Commission and prion (TSE) disease reporting 2011

http://transmissiblespongiformencephalopathy.blogspot.com/2011/05/oie-terrestrial-animal-health-standards.html

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 then Central Bureau............

http://www.oie.int/eng/Session2007/RF2006.pdf

SO, the OIE BSE MRR status, is based on whatever information and data the given BSE countries give them to go by.

LIKE i have stated time and time again, OIE BSE MRR policy is bought and paid for by your local cattle dealer.

THE BSE MRR policy is nothing more than a legal tool to trade TSE globally.

I urge that the BSE MRR policy be repealed, and the BSE GBR risk assessments be upgraded to include all strains of TSE, including the USA H-BASE, but to even go further, and include all TSE in ALL species. ...TSS

http://madcowtesting.blogspot.com/

Wednesday, November 17, 2010

MAD COW TESTING FAKED IN USA BY Nebraska INSPECTOR Senator Mike Johanns STATE Neb. inspector accused of faking mad cow tests

Published November 17, 2010

http://madcowtesting.blogspot.com/2010/11/mad-cow-testing-faked-in-usa-by.html

Thursday, November 18, 2010

UNITED STATES OF AMERICA VS GALEN J. NIEHUES FAKED MAD COW FEED TEST ON 92 BSE INSPECTION REPORTS FOR APPROXIMATELY 100 CATTLE OPERATIONS

http://bse-atypical.blogspot.com/2010/11/united-states-of-america-vs-galen-j.html

Saturday, June 25, 2011

Transmissibility of BSE-L and Cattle-Adapted TME Prion Strain to Cynomolgus Macaque

"BSE-L in North America may have existed for decades"

http://transmissiblespongiformencephalopathy.blogspot.com/2011/06/transmissibility-of-bse-l-and-cattle.html

Sunday, June 26, 2011

Risk Analysis of Low-Dose Prion Exposures in Cynomolgus Macaque

http://transmissiblespongiformencephalopathy.blogspot.com/2011/06/risk-analysis-of-low-dose-prion.html

Thursday, June 2, 2011

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

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

Monday, June 20, 2011 2011

Annual Conference of the National Institute for Animal Agriculture ATYPICAL NOR-98 LIKE SCRAPIE UPDATE USA

http://nor-98.blogspot.com/2011/06/2011-annual-conference-of-national.html

Monday, June 27, 2011

Comparison of Sheep Nor98 with Human Variably Protease-Sensitive Prionopathy and Gerstmann-Sträussler-Scheinker Disease

http://prionopathy.blogspot.com/2011/06/comparison-of-sheep-nor98-with-human.html

Monday, November 30, 2009

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

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

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

Friday, February 11, 2011

Atypical/Nor98 Scrapie Infectivity in Sheep Peripheral Tissues

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

Thursday, November 18, 2010

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

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

Sunday, October 3, 2010

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

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

Wednesday, July 06, 2011

Swine Are Susceptible to Chronic Wasting Disease by Intracerebral Inoculation

(see tonnage of mad cow feed in commerce USA...tss)

http://chronic-wasting-disease.blogspot.com/2011/07/swine-are-susceptible-to-chronic.html

Monday, June 27, 2011

Zoonotic Potential of CWD: Experimental Transmissions to Non-Human Primates

http://chronic-wasting-disease.blogspot.com/2011/06/zoonotic-potential-of-cwd-experimental.html

Please see the following warning from CDC about prion TSE consumption in North America ;

Thursday, May 26, 2011

Travel History, Hunting, and Venison Consumption Related to Prion Disease Exposure, 2006-2007 FoodNet Population Survey

Journal of the American Dietetic Association Volume 111, Issue 6 , Pages 858-863, June 2011.

http://transmissiblespongiformencephalopathy.blogspot.com/2011/05/travel-history-hunting-and-venison.html

CANADA GREENS CALL FOR 100% BSE MAD COW TESTING

Greens call for ban on federal GMO research Apr 10, 2011 11:45 PM

snip...

The party said it would also aim to tighten Canada's testing net for bovine spongiform encephalopathy (BSE) in slaughter cattle by implementing "100 per cent" testing of all slaughtered animals, but only "as soon as the process of detecting BSE in blood samples is perfected." The party also calls for ensuring no "animal byproducts" are used in ruminant animal feed....

snip...

http://www.albertafarmexpress.ca/issues/story.aspx?aid=1000407400

Green Party MPs will develop a National Agricultural and Food Policy which:

Improves Food Safety by:

• Amending the Canadian Food Inspection Agency mandate to remove any obligation to promote Canadian agri-business, ensuring the focus is on food safety and food safety only, with enhanced resources for inspection and monitoring.

• Ensuring the quality and wholesomeness of food by strengthening the monitoring of pesticides, herbicides, fungicides, growth hormones, non-therapeutic antibiotics and insecticides in food production, processing and storage, with the goal of an orderly reduction in detectable residues of these substances until they reach undetectable limits.

• Establishing federally funded, community-guided school lunch programs across Canada to ensure that our children have daily access to healthy local food and can learn about sustainable food production and healthy eating.

• Strengthening Plant Protection and Health of Animals Programs with measures to ensure the integrity of farm food products.

• Improving and strengthening the Canadian Organic Standard.

• Providing transitional assistance for those switching to certified organic farming practices.

• Ensuring that no animal by-products are used in ruminant animal feed.

• Strengthen testing for BSE by implementing 100% testing (testing of every slaughtered animal) as soon as the process of detecting BSE in blood samples is perfected.

Vision Green April 2011

http://greenparty.ca/files/attachments/april_2011_vision_green.pdf

THANK YOU !!!

IN THE USA, we use the SSS policy, or the 'don't look, don't find' policy, or what i also call the ''obex only'' diagnostic criteria for how not to find a mad cow. The USA pollutes its oceans, bays, gulf, and rivers, and allows others to pollute them too. Allows industry to pollute the air we breath. Texas has now become the USA nuclear dumping grounds, thanks to our good gov perry. the USA federal gov. dumps all funding for the mad cow TSE prion diseases, while at the same time, human and animal TSE in North America are mutating, spreading, and cpsCJD (classification pending sporadic creutzfeldt jakob disease) is rising in young and old. i don't understand the insanity of it all. ...

All Other Emerging and Zoonotic Infectious Diseases CDC's FY 2012 request of $52,658,000 for all other emerging and zoonotic infectious disease activities is a decrease of $13,607,000 below the FY 2010 level,

which includes the elimination of Prion activities ($5,473,000),

a reduction for other cross-cutting infectious disease activities, and administrative savings. These funds support a range of critical emerging and zoonotic infectious disease programs such Lyme Disease, Chronic Fatigue Syndrome, and Special Pathogens, as well as other activities described below.

http://www.cdc.gov/fmo/topic/Budget%20Information/appropriations_budget_form_pdf/FY2012_CDC_CJ_Final.pdf

" the FY 2010 level, which includes the elimination of Prion activities ($5,473,000), "

USDA MAD COW PROBLEMS SOLVED $$$

Canadian Researchers Receive $2.9 Million to Protect Against Prion Disease Outbreaks, Develop Novel Therapies to Treat Alzheimer’s, Parkinson’s and ALS

Scientists find increasing connection between development of prion disease and common human neurodegenerative disorders

July 13, 2011 (Vancouver, BC) – Collaborative research groups at nine different universities, involving 55 different investigators across Canada, are poised to make significant advances in the understanding of prion and prion-like diseases in humans and animals. These include the development of an oral vaccine to help stop the spread of chronic wasting disease (CWD) in wild deer and elk populations and novel approaches to treat human neurodegenerative disorders like ALS (Lou Gehrig's disease), Alzheimer’s and Parkinson’s diseases, thanks to $2.9 million in funding announced by PrioNet Canada.

The goal of the funding which supports 11 projects is two-fold, explains Dr. Neil Cashman, Scientific Director of PrioNet Canada, one of Canada’s Network of Centres of Excellence. “By working with our partners, we aim to continue to protect Canada against classical prion diseases like chronic wasting disease and mad cow disease (bovine spongiform encephalopathy or BSE), and we’re also providing benefit to Canadians through the development of innovative therapeutics to treat neurodegenerative diseases like Alzheimer’s, Parkinson’s and ALS.”

The researchers will use the funds to better understand the biology of prion disease, to develop strategies to manage prion disease outbreaks and minimize the impacts, and to apply learnings of prion diseases to the treatment of human neurodegenerative disorders.

Prion diseases are fatal, infectious and transmissible diseases of humans and animals associated with a ‘sponge-like’ degeneration of brain tissue. In animals, the most common prion diseases include BSE, scrapie in sheep and goats, and CWD in deer and elk. In 2003, Canada’s beef and related industries were faced with worldwide closing of trade after a domestic case of BSE was found in Alberta. Canada’s economic loss stemming from this event is estimated at more than $6 billion. Some examples of prion diseases in humans include fatal and sporadic familial insomnia, Creutzfeldt-Jakob disease (CJD) and its many varieties, and Kuru. Some examples of the ground-breaking work supported by PrioNet’s recent funding include:

• Immunotherapies to treat ALS: Five PrioNet researchers at the University of British Columbia, University of Alberta and University of Toronto are focusing on a newly-recognized molecular mechanism of ALS, a misfolded protein called SOD-1. By identifying the parts of the protein that are exposed when it is misfolded in disease, researchers are able to design immunotherapies that can target those areas, interrupting the slow progression of paralysis and eventual death characterized by the disorder. Two animal models have already demonstrated responsiveness to the new immunotherapies and work is now underway to develop a therapy for humans. “We are hoping these discoveries could prove to be a magic bullet for ALS,” said Dr. Cashman, who serves as principal investigator for the multi-disciplinary research team.

• Oral vaccine to control chronic wasting disease in the wild: Prion diseases like chronic wasting disease are continuing to spread throughout the Canadian prairie’s wild deer and elk populations and ten PrioNet researchers in Saskatoon and British Columbia are working on an oral vaccine to stop the spread. “The danger is that prion diseases are evolving and new strains are emerging,” noted Dr. Scott Napper, a Research Scientist with the Vaccine and Infectious Disease Organization in Saskatoon and principal investigator on the project. Dr. Napper’s group is focusing on an oral vaccine that can withstand extreme temperatures and will effectively attract elk and deer in the wild. Similar oral vaccines are already used to control rabies in Eastern Canada, where food packets containing the vaccine are widely distributed for consumption by fox and raccoon populations.

• Framework to minimize the impact of chronic wasting disease: Principal investigator Dr. Ellen Goddard from the University of Alberta along with nine co-investigators are working to identify the risk factors associated with chronic wasting disease in wild deer and elk populations, how they can be managed and what public policy recommendations should be put in place to try and mitigate the effects. The primary goal is to monitor the many unknowns that remain about the impact of CWD in the wild, such as the potential risk to hunters who consume infected animals and the potential interface between wild and domestic animals. “The risk management framework around BSE showed that even though countries were aware of the disease in their cattle, they completely underestimated the economic impact and the public response,” notes Dr. Goddard. “We’re doing the work ahead of the game while CWD is still manageable and while effective policies can be put into place to control it, to help anticipate and prevent the impacts.”

• Understanding ‘good versus bad’ prions in order to develop drugs: The first step to designing drugs to treat prion and prion-like diseases is to understand how prion proteins change shape when they become “misfolded” in disease. Dr. Christoph Borchers, a Professor in the Department of Biochemistry and Microbiology and Director of the University of Victoria-Genome BC Proteomics Centre is collaborating with researchers from the University of Alberta and University of Western Ontario to characterize the changes that occur to the three-dimensional structure of prion fibrils (small, nerve-like fibres) as well as the molecular mechanisms that lead to those changes. Using a combination of protein chemistry and mass spectrometry, they are working to explain what occurs when a ‘good’ prion protein changes to a ‘bad’ one during disease development. The information is crucial to designing drugs that can interfere with those changes, effectively curbing the spread of prion and prion-like diseases.

About PrioNet Canada (www.prionetcanada.ca) One of Canada’s Networks of Centres of Excellence, PrioNet Canada is a pan-Canadian research network that is developing strategies to help solve the food, health safety, and socioeconomic problems associated with prion diseases. The network brings together academia, industry, and public sector partners through its multidisciplinary research projects, training programs, events, and commercialization activities to help derive maximum socioeconomic benefits for Canadians. PrioNet is hosted by the University of British Columbia and the Vancouver Coastal Health Research Institute in Vancouver.

- 30 -

Media information or to set up interviews: Gail Bergman or Christina Vetro Gail Bergman PR Tel: (905) 886-1340 or (905) 886-3345 E-mail: info@gailbergmanpr.com

Last Updated: 7/13/2011 11:27:59 AM

http://www.prionetcanada.ca/detail.aspx?menu=12&dt=293779&app=70&cat1=211&tp=12&lk=no

Friday, March 4, 2011

Alberta dairy cow found with mad cow disease

http://transmissiblespongiformencephalopathy.blogspot.com/2011/03/alberta-dairy-cow-found-with-mad-cow.html

Wednesday, August 11, 2010

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

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

Thursday, August 19, 2010

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

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

Thursday, February 10, 2011

TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY REPORT UPDATE CANADA FEBRUARY 2011 and how to hide mad cow disease in Canada Current as of: 2011-01-31

http://madcowtesting.blogspot.com/2011/02/transmissible-spongiform-encephalopathy.html

Wednesday, December 22, 2010

Manitoba veterinarian has been fined $10,000 for falsifying certification documents for U.S. bound cattle and what about mad cow disease ?

http://usdameatexport.blogspot.com/2010/12/manitoba-veterinarian-has-been-fined.html

Saturday, March 5, 2011

MAD COW ATYPICAL CJD PRION TSE CASES WITH CLASSIFICATIONS PENDING ON THE RISE IN NORTH AMERICA

http://transmissiblespongiformencephalopathy.blogspot.com/2011/03/mad-cow-atypical-cjd-prion-tse-cases.html

TSS

Atypical Prion Diseases in Humans and Animals 2011

2011-05-23T10:52:00.000-07:00

Top Curr Chem (2011)

DOI: 10.1007/128_2011_161

# Springer-Verlag Berlin Heidelberg 2011

Atypical Prion Diseases in Humans and Animals

Michael A. Tranulis, Sylvie L. Benestad, Thierry Baron, and Hans Kretzschmar

Abstract

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

M.A. Tranulis (*)

Norwegian School of Veterinary Science, Oslo, Norway

e-mail: Michael.Tranulis@nvh.no

S.L. Benestad

Norwegian Veterinary Institute, Oslo, Norway

T. Baron

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

H. Kretzschmar

Ludwig–Maximilians University of Munich, Munich, Germany

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

snip...

Classical scrapie in small ruminants, the archetypal animal prion disease [66], and CWD in cervids are the only known prion diseases that spread effectively within a species, under natural (free-ranging wild population) or near-natural (extensive husbandry) conditions [67–70]. Spread may be horizontal through direct contact or shared environments [71, 72], or vertical from mother to offspring during the pre- or neonatal period [73–75]. Although these diseases clearly illustrate that prion diseases can behave as true infectious maladies, they could, ironically, turn out to be exceptions to the rule rather than typical. Predators have the potential to be exposed to ruminant prion disease and, as evident with the BSE-C agent, possibly develop prion disease. A recent study of predators in a CWD endemic area of Wisconsin did not provide evidence of a transmission of CWD prions across species barriers [76]. For a prion disease to be sustained as infectious within a population, it seems that the infectious prion must be present at relatively high levels in the peripheral tissues of affected animals, most notably in the digestive Atypical Prion Diseases in Humans and Animals tract and its associated salivary glands and lymphoid aggregates. CWD transmits effectively, with saliva [71, 72, 77], feces [78], and urine [79] as primary vehicles, either through contact or via the environment. Protease-resistant PrP of cervid origin has been detected in water samples taken from a CWD endemic area [80].

snip...

With the discovery of ruminant prion diseases that resemble sporadic human prion disease, a certain element of “balance” in the epidemiology of prion disease could be established. However, the logic of this could also be reversed, and an important question could be raised: might the low level occurrence of spontaneous farm animal prion disease underlie one or more forms of human prion disease, which are currently misinterpreted as spontaneous? This major epidemiological and public-health issue will be the focus of discussion in this chapter.

3 Atypical/Nor98 Scrapie

During a period of enhanced awareness regarding sheep scrapie in the late 1990s, a few suspect scrapie cases, with unusual clinicopathological features, were identified in Norway, and were subsequently named Nor98 [45]. The first case appeared in Eastern Norway, until then considered to be a scrapie-free region. Intriguingly, old and healthy sheep in the same flock were found to be carrying PrP-genotypes conferring high susceptibility to scrapie, while the affected animal had a PrP genotype rarely seen in classical scrapie [117]. The predominant clinical symptom was progressive ataxia. While in classical scrapie the predominance of pathology is in the brain stem, the unusual Nor98 cases showed pathology and PrPSc accumulation in the cerebral and cerebellar cortices. The glycoprofile of proteinase-resistant PrPSc from all the unusual cases also differed from classical scrapie, with multiband pattern and a characteristic lower band of around 11 kDa, not previously described in animal prion diseases (Fig. 1). In the brain stem, pathology and PrPSc accumulation was mild or even below detection limits [45]. This lesion profile has proved to be consistent for atypical/Nor98 scrapie [118–121]. Furthermore, when PrPSc is detectable in the brain stem in atypical cases, it is mainly restricted to the neuropil of the spinal tract nucleus of the trigeminal nerve, as sparse and diffuse staining, and/or as globular staining in the white matter, which is occasionally pronounced along the spinocerebellar tracts.

In addition to the difference in lesion profile, the pattern of PrPSc deposits in such atypical scrapie cases also differs from that seen in classical scrapie cases [109, 122]. In classical scrapie, a stellate pattern of PrPSc deposits is particularly prominent in the granular layer of the cerebellum, while in atypical/Nor98 scrapie a widespread, diffuse, synaptic type of staining can be observed in the molecular or the granular cell layers or both, and may be variably associated with globular staining in the white matter.

In the cerebral cortex, classical cases display a stellate, perivascular, and frequently intraneuronal PrPSc staining, while in atypical/Nor98 cases a diffuse laminar staining dominates. In some atypical/Nor98 cases, multifocal dense plaque-like aggregates can be seen in the white matter tracts [118].

One case of atypical/Nor98 scrapie has been reported in which all brain sections appeared negative for immunohistochemical PrPSc; however, a faint staining could be observed in the granular layer by use of the PET-blot technique [109, 122]. Interestingly, there appears to be no correlation between the degree of PrPSc staining and the disease phenotype, regardless of age and PrP genotype.

Since the obex area and especially the dorsal motoric nucleus of the vagus nerve (DMNV) were previously considered the tissue of choice for scrapie diagnostic purposes, the Nor98 cases might easily have escaped identification. At around the same time that the first atypical/Nor98 cases were discovered, a number of atypical scrapie cases were identified through pan-European screening programs, designed particularly for detecting BSE in small ruminants. Following a report of German and French cases [46], further reports came from many other European countries [120, 123–129], as well as The Falkland Islands [130], USA [131], New Zealand [132], Australia [133], and, most recently, Canada [134]. According to data from the European Surveillance Program for TSE in small ruminants, atypical/Nor98 scrapie has been identified in more than 20 European countries [135], with a surprisingly uniform prevalence (about 6–8 cases per 10 000 tests), which contrasts with the more variable and clustered occurrence of classical scrapie. A study of formalin-fixed archival brain material has back-dated atypical/Nor98 scrapie in the UK to at least 1987 [136], demonstrating that atypical/Nor98 scrapie has existed in the small ruminant population for years without being detected.

Diagnostic kits for rapid detection of atypical/Nor98 scrapie have recently been evaluated by the European Food Safety Authority (EFSA), with five out of nine tests being approved [137]. Since tests that did not achieve EFSA approval, due to lack of sensitivity, will be in use until the end of 2010, it is reasonable to assume that atypical/Nor98 scrapie is underdiagnosed. The underlying problem of detecting atypical/Nor98 scrapie seems not only related to the selection of tissue for analysis, but also the relative PK-sensitivity of PrPSc generated in this disease [48, 119, 138], a property that continues to be preserved following transmission into mice. In the first study of transmission of atypical/Nor98 scrapie to transgenic mice expressing ovine PrP, similar lesion profiles, PrPSc deposition patterns, incubation periods, and PrP-glycoprofiles were reported following inoculation from isolates obtained from three Norwegian and ten French atypical scrapie cases, suggesting that a single, unique prion strain was responsible for causing the atypical/Nor98 type of scrapie [139]. This study has been extended to British atypical isolates, and the results again confirm the uniformity in transmission characteristics of atypical/Nor98 isolates [140].

Detailed mapping of the PrP-fragments, as revealed in Western Blots after PK treatment, has demonstrated, despite some small discrepancies, a unique banding pattern, with a characteristic lower band (band C after PNGase-F treatment) of about 11 kDa [44, 45, 48] or 7 kDa [138], consisting of an internal PrP-fragment. The N-terminus of the 11-kDa fragment has been accurately mapped to amino acid (aa) 85–90, since several mAbs with known linear epitopes are available for this region of the PrP. The C-terminus of the fragment is predicted to be around aa 185–190, assuming no post-translational modifications. However, there are only few mAb available to the aa 155–200 region in PrP, and thus precise epitope mapping of the C-terminus of this PrP-fragment is currently problematic. The 11- kDa band is a consistent diagnostic hallmark in cases of atypical/Nor98 scrapie, not only in sheep, but also in goats [141].

The occurrence of classical scrapie in sheep is modulated by three polymorphisms, at codons 136 (alanine/valine, A/V), 154 (arginine/histidine, R/H), and 171 (glutamate/arginine/histidine, Q/R/H) in the gene that encodes PrP, PRNP [142–144]. The frequency of these, and other PrP polymorphisms, varies significantly between breeds and the different polymorphisms are generally mutually exclusive. The valine polymorphism at codon 136 results in the major disease promoting allele V136R154Q171 (VRQ), with homozygous VRQ/VRQ animals the most susceptible. The presence of arginine (R) at codon 171 (ARR allele) has been shown to be significantly associated with a reduction in the probability of classical scrapie occurrence, conveying a relative resistance, thereby enabling markerassisted breeding for resistance towards classical scrapie [145, 146].

However, atypical/Nor98 scrapie seems to occur most frequently in sheep with PrP genotypes considered to be less susceptible, while apparently sparing flock-mates carrying high susceptibility PrP genotypes [45]. A large proportion of atypical/Nor98 cases carry at least one AHQ allele. Moreover, the presence of phenylalanine (F) at codon 141 (wt-allele leucine, L), giving rise to the AF141RQ (AFRQ) allele, is also strongly associated with this type of scrapie [147–149]. A schematic presentation of allelic modulation of susceptibility for classical and atypical/Nor98 scrapie is given in Fig. 2. Interestingly, atypical/Nor98 scrapie has been very rarely recorded in sheep carrying the VRQ allele, and only in combination with a disease promoting AHQ or AFRQ allele, while several cases have been seen in sheep with the ARR/ARR genotype [150]. In a study of genetic risk for atypical/Nor98 scrapie involving 248 cases [151], the most susceptible PrP genotypes were found to be ALHQ/ALHQ, ALHQ/AFRQ, and AFRQ/AFRQ, while heterozygotes ALHQ/ALRQ and AFRQ/ALRQ were less susceptible. This result concurs with data from other studies [44, 148, 150] and also highlights the previously reported [150] risk of atypical/Nor98 scrapie in animals with the ALRR/ ALRR genotype, which are enriched in marker-assisted breeding.

Although some data indicate a protective effect of the VRQ allele towards atypical/Nor98 scrapie, the first transmission to transgenic mice (line tg338) was achieved with mice carrying the ovine PrP VRQ/VRQ genotype on a PrP null background. However, these mice over-expressed PrP by eight- to tenfold, compared to the level in sheep brain [139]. In a subsequent study, aimed at defining the transmission characteristics in more detail, three lines of TgOvPrP4 mice were used, with neuron-specific expression of the ovine ARQ/ARQ genotype at approximately 0.25 times, 1.5 times, and 6 times the level in sheep. In this study, transmission of atypical/Nor98 scrapie was shown to be more strongly modulated by host PrP expression level and the genotype of the inoculum than is observed with classical scrapie or BSE-C [152].

Epidemiological analyses of atypical/Nor98 scrapie in different countries [135, 150, 153, 154] have resulted in a fairly uniform epidemiological profile being described. Atypical/Nor98 scrapie is widely distributed geographically, without clustering, and normally only one or very few cases are seen, even in flocks of several hundred animals. Additionally, atypical/Nor98 cases are generally older than classical scrapie cases and a significant proportion of the cases have been identified through screening-programs and/or by analysis of fallen stock, while this is uncommon for classical scrapie [118]. Case-control studies [154, 155] of atypical/ Nor98 scrapie have failed to identify epidemiological evidence to indicate an infectious behavior, whereas contact and purchase are important risk factors for classical scrapie [67]. However, epidemiological analysis and modeling of sheep prion disease is far from trivial. For a comprehensive review of this topic, see [156].

In 1980, Gibbs and co-workers [157] transmitted kuru, CJD, and scrapie to squirrel monkeys by the oral route. The scrapie isolate they used had a complex passage history, with nine serial passages from sheep to goat, followed by three serial passages in mice, and finally three serial passages in hamster. Two monkeys were fed brain, kidney, and spleen from scrapie-infected hamsters for 3 days. The monkeys succumbed to spongiform encephalopathy after 25 and 32 months. Notably, the incubation period in a squirrel monkey intracerebrally inoculated with brain material from a scrapie-diseased goat was 31 months and that of intracerebral inoculation of mouse-adapted scrapie isolates varied from 14 to 31 months. Thus the incubation periods observed after oral inoculation were comparatively short, indicating that the oral route of transmission could be effective, at least in combination with large doses of infective material. This significant study demonstrated that a rodent-adapted scrapie strain can be transmitted to non-human primates via the oral route and also provides a pertinent reminder of the pathogenic potential of scrapie. Transmissions of classical and atypical/Nor98 scrapie to mice have produced disease profiles and PrPSc types that are reassuringly different from those seen in BSE and in human prion disease [59, 139, 152, 158]. However, transmission of a primary classical scrapie isolate from Romanov sheep to C57BL/6 mice produced a lesion profile and PrPSc type conspicuously similar to those seen after transmission of sCJD and iCJD to the same line of mice, while this was not the case after transmission of a mouse-adapted scrapie strain included in the same study [158]. Thus, despite the lack of recognized epidemiological connections between sheep scrapie and human prion disease [159], and considering the variability in strain characteristic of sheep scrapie, it should be noted that we currently have no effective experimental models for estimation of human risk related to oral exposure to such pathogens.

4 Atypical BSE

Until 2004 it was believed that BSE was a unique disease, due to a single major strain of TSE agent that was propagated in cattle by recycling in contaminated meat-and-bone meal. This opinion had been strongly supported by the identification of a unique strain of transmissible agent, as defined by its features following transmission of the disease in inbred wt mouse models that had been extensively used in the UK to demonstrate that scrapie in sheep and goats could involve a variety of different strains [160, 161]. Transmission to mouse lines, such as RIII, C57BL, or VM, of different bovine isolates, including those from different countries, revealed a uniform behavior, as shown by incubation periods of the disease, distribution of spongiform changes, and the distribution and features of PrPSc deposits. This uniformity of the disease in cattle was also supported by the findings of the same distribution of lesions in the brains of cattle, with the medulla oblongata predominantly involved, including at different times of the epidemic in cattle in the UK, or in other European countries [162–164].

In 2004, this established “fact” that BSE was a unique single strain infection, was abruptly challenged when two countries reported the occurrence of a few cases of BSE in older cattle that showed deviant features of the disease. In France, three cases were reported that showed an unusually high molecular mass of PrPSc by Western blot studies, indicating a protease cleavage site distinct from that seen in cattle with “classical” BSE (BSE-C) [64]. This was unlikely to be a reflection of phenotypic variations since a number of studies had previously shown that the PrPSc molecular features, notably the protease cleavage site, was a very reliable characteristic of BSE-C, even preserved upon transmission to other species, such as in variant CJD in human [22], or, experimentally, in sheep or in mice [28, 165–168]. A second report from Italy described two cases from cattle, but in these cases the PrPSc molecular mass was slightly lower than that observed in BSE-C, and, more strikingly, the proportion of the diglycosylated band was significantly lower [65]. In this report, the differences from classical BSE were further supported by histopathological analysis that revealed that the distribution and nature of lesions in the cattle brains differed distinctly from those previously described during the BSE-C epizooty. Not only were the lesions much more abundant in the cortical regions of the brain, in contrast with the preferential location in the brain stem in BSE-C, but were also characterized by the presence of amyloid plaques which are not observed in BSE-C. Due to this last characteristic, the disease was termed Bovine Amyloidotic Spongiform Encephalopathy (BASE). As histopathological data are not always available, the two diseases identified in France and Italy were soon referred to as either H-type BSE or L-type BSE, based on the differences in PrPSc molecular masses identified after Western blot analysis [169]. Importantly, in all five cases, analysis of the coding sequence of the PRNP gene did not reveal any unusual features compared with the known PRNP sequence in cattle, and thus a genetic origin of such cases seemed unlikely.

These unexpected observations prompted further investigations, initially directed towards the confirmation of the original findings, including in other countries. Other “atypical” cases of BSE in cattle were rapidly identified in a number of different countries in Europe (Germany, Netherlands, Poland, Denmark, Ireland, United Kingdom, Sweden, Austria) [167, 168, 170–173] and also in Japan [161], USA [174, 175], and Canada [176] (Table 1). Questions immediately arose about the possible origins of such cases. Interestingly, some of the cases had been diagnosed in countries considered at low risk of exposure to contaminated meatand- bone meal such as Sweden in Europe, or the USA. The findings were also confirmed in Italy, where two additional BASE cases (BSE-L) were recognized and, to a larger extent, in France where the highest number of “atypical” cases have been identified to date since the implementation of active surveillance by rapid tests in 2000 (a total of 27 cases, 14 H-type and 13 L-type). Indeed, all cases recognized so far have been identified after initial diagnosis by rapid tests through the active surveillance programs that encompass exhaustive surveillance in adult cattle in Europe since 2001. This large-scale screening has certainly been essential for the discovery of such cases, which hardly would have been identified by passive surveillance, with the only exception being the finding of a single H-type BSE case in a 17-year-old zebu kept in a zoological park in Switzerland, in which clinical signs triggered neurological investigations, including BSE testing [177].

All the available studies to date have demonstrated that the cases identified in different countries have molecular features that are extremely consistent with those of the very first cases diagnosed in France and Italy. Among these studies, a collaborative European network study of atypical cases from six European countries (France, Italy, Netherlands, Germany, Poland, and Sweden) confirmed the migration properties and glycosylation profiles (glycoprofiles) of the H- and L-type isolates (Fig. 3). The presence of H-type BSE could also be detected by the differential binding of mAb specific for N- and more C-terminal PrP regions, indicative of the existence of two PrPSc populations differing by their N-terminal cleavage sites [178] (Fig. 3). In addition, this study revealed that both H-type and L-type BSE have enhanced protease sensitivities at pH 8, compared with BSE-C isolates. These properties appear to be consistent within each BSE type, independent of geographical origin, and although not all these criteria have been investigated in all the studies, this was also confirmed in cases of H-type BSE reported in the UK, USA, and Canada, and for cases of L-type BSE diagnosed in Japan and Canada. Thus, altogether these studies provided reliable criteria for identifying two atypical BSE forms, in addition to classical BSE.

Importantly, diagnosis of BSE in cattle is not always followed by further analyses to identify whether the case is classical or atypical. This contrasts with the diagnosis of prion disease in sheep and goats in Europe, following which further molecular investigations are undertaken on a regulatory basis, in order to identify possible unusual features that could indicate infection by the BSE agent. This difference in approach suggests that the number of atypical BSE cases in cattle among those reported by the OIE, as shown in Table 1, is certainly underestimated. The largest published study was performed on cattle in France between 2001 and 2007, during which 13 atypical cases (7 H-type and 6 L-type) were identified among 645 BSE cases [179]. During the 6-year period, 17.1 million rapid tests were performed, including 3.6 million animals over 8 years old. Thus, the estimated frequencies of H-type and L-type BSE were 0.41 and 0.35 per million adult cattle tested, respectively (1.9 and 1.7 in cattle over 8 years old). The most important information obtained in this study was the striking difference between the distribution by year of birth of atypical and classical cases detected during 2001–2007. Whereas the cases with classical BSE clearly indicated exposure to the classical BSE agent during 1993–1996 in France, one or two cases born each year were eventually identified as having atypical BSE (both H-type and L-type) at a mean age of 12 years. Overall, whereas the frequency of such atypical cases, although possibly underestimated, is certainly low, another relatively large series of atypical BSE cases (mostly of L-type) was also reported in Poland in cattle over 9 years old [172]. Together with the finding of atypical cases in some countries that were considered at very low risk of foodborne classical BSE, these data strongly argue that such atypical BSE cases represent sporadic TSE, as are most cases of CJD in humans. The PRNP gene has not been characterized for all cattle diagnosed with atypical BSE. However, genetic analyses have so far failed to identify any polymorphisms specifically associated with atypical BSE in the gene that encodes PrP [64, 65, 161, 164, 169, 175, 177]. Interestingly, a single case was reported in the USA with HtypeWestern blot features, which also had an E211K mutation, similar to the mutation E200K in humans, the most frequent mutation associated with gCJD [174]. Although this finding is of interest regarding our basic knowledge about the possible relationship between the PrP sequence and the pathogenesis of such diseases, it is unlikely to be of particular significance in cattle populations, since it seems that this mutation is quite rare, as it was not detected in a study of 6,062 cattle in the USA [180]. As well as the PRNP coding sequence, one or two copies of a distinct PRNP haplotypewere identified in five of six atypical BSE cases from France, Canada, and USA [170, 181]. This haplotype spans a portion of PRNP that includes part of intron 2, the entire coding region of exon 3, and part of the three prime untranslated region of exon 3 (13 kb), suggesting that a genetic determinant in, or near, the PRNP gene may influence susceptibility of cattle to atypical BSE. Also, whereas two regulatory region polymorphisms in the PrP gene of cattle have been reported to be associated with resistance to BSE, it has also been shown that the promoter polymorphism correlationwas specific to classical BSE, and that atypical BSE or experimentally inoculated TSE bypass the site of influence of the polymorphisms [182]. This suggests that genetic features involved in classical or atypical BSE could be linked to the different pathogeneses of the diseases, putatively in relation to either their acquired or sporadic origins.

Another line of investigation that followed the initial discovery of the two atypical forms of BSE was related to the potential transmissibility of the agent from such cases, and biological features of the TSE agents involved. Transmission of H-type BSE through a species barrier was first demonstrated using C57Bl/6 wild-type mice [183]. Detailed studies using transgenic mice expressing bovine or ovine PrP eventually demonstrated that H-type BSE and L-type BSE exhibit different biological and molecular features in these mouse models, and that both also differed from the wellknown strain isolated from classical BSE [169, 184–188]. In particular, the distinct properties of PrPSc in cattle identified by Western blot were maintained following transmission to transgenic mice expressing bovine PrP, in association with distinct incubation periods of the disease, as well as distribution and features of PrPSc deposits in the mouse brains [169, 184–188]. Transmission of H-type BSE into C57Bl/6 wildtype mice demonstrated the presence of a second, more C-terminally cleaved, formof PrPSc (PrPres #2), which, in unglycosylated form, migrated at approximately 14 kDa and could be specifically detected using C-terminal antibodies, as in the cattle brain [189]. Overall, these data clearly indicate that the three phenotypes of BSE in cattle are associated with three different major strains of transmissible agents.

To date, few studies have been published with regard to the transmission of these atypical BSE forms in cattle. Intra-species transmission of an Italian case of L-type BSE between Friesian and Alpine brown cattle was demonstrated using intra-cerebral inoculation, and the L-type molecular features were reproduced, as well as the presence and distribution pattern of amyloid plaques in the cattle brains [190]. This was associated with a disease phenotype characterized by mental dullness and progressive amyotrophy, suggestive of amotor neuron disorder, in contrast with the overreactivity and hypersensitivity in the absence of muscle changes, which are observed in cattle infected by a classical BSE isolate [190]. Transmission between cattle by the intra-cerebral route was also reported from other L-type isolates identified in Japan [191] and Germany [197] also from H-type cases from the Netherlands or Germany [192, 197] that also confirmed that the H-type molecular features were maintained in experimentally infected cattle. However, the extent to which these two atypical forms of BSE could also be transmitted to cattle by the oral route is currently unknown, and this information is essential in order to estimate more precisely the potential risks associated with these rare BSE isolates.

However, experimental studies in mouse models have already generated the hypothesis that such putatively sporadic cases may have been the origin of the foodborne epizooty of classical BSE, possibly after first recycling through an intermediate species [184, 188, 198]. Inoculations of C57Bl/6 and SJL wild-type mice with an Italian L-type BSE isolate resulted in some intriguing observations [188]. Unlike with inoculation with a classical BSE isolate, in these inoculations no evidence of transmissionwas detected during the first passage; clinical disease and brain lesionswere absent and PrPSc could not be detected either by Western blots or immunohistochemistry. However, a second passage from a pool of brain homogenates from these mice, and inoculated into the same mouse lines by both intra-peritoneal and intra-cerebral routes, resulted in clinical disease associated with brain lesions. Surprisingly, the molecular features, as well as the distribution of spongiform changes and PrPSc deposits, showed considerable similarities with those found in the same mouse lines when infected with classical BSE. It was thus assumed that either (1) classical BSE was present as a minor component in the initial L-type BSE inoculum and had been propagated in these mice or that (2) in the mouse background the L-type BSE had converted into classical BSE. More recently, the emergence of a strain indistinguishable fromclassical BSE has also been described following serial passages of BSE-H in some C57Bl/6 mice, although BSE-H can also be transmitted and maintained with the characteristic H-type properties in this mouse model [189, 198]. Another study of L-type BSE transmitted to a transgenic mouse line (tg338) over-expressing the ovine PrP (VRQ allele), also showed a shift in disease phenotype, with molecular and lesional features similar to those observed in these mice following transmission of classical BSE [184]. These results suggest the theoretical possibility that an early event, preceding the amplification of the classical BSE agent in cattle, could have been recycling of a TSE agent primarily present in cattle but modified through passage in an intermediate host such as sheep. However, it remains to be demonstratedwhether these two series of observations reflect the genuine identification of a common TSE agent present in both L-type and classical BSE in cattle, or if this represents phenotypic convergence following transmission in mouse models. Full characterization of the biological properties of the TSE agents produced in these experiments will help to clarify this issue.

Although, the characteristics of transmission of L-type BSE in sheep still remain to be described, it should be noted that different results were obtained in another transgenic mouse line (TgOvPrP4) expressing the ARQ allele of the ovine PrP at a lower level and under a different promoter [193]. In this mouse line, the molecular and lesional features of L-type BSE remained clearly distinct from those observed following transmission of classical BSE [193]. Results from this study had similarities to those obtained following transmission of the Stetsonville TME isolate in the same mouse model, having first been transmitted to cattle. This has been further supported by a recent study showing the transmissibility in Syrian hamsters of both L-type BSE and TME-in-cattle, and their similar molecular features in this model, as well as in bovine transgenic mice [199]. It can thus be hypothesized that outbreaks of TME in minks, which are occasionally observed in captive minks as a foodborne disease of unknown origin, might actually be caused by the consumption of food derived from cattle affected with L-type BSE. If confirmed, this would demonstrate the oral transmissibility of this atypical BSE form in a non-ruminant species. This hypothesis appears to have gained further credence from the recent observation of phenotypic similarities between TME in cattle and L-type BSE transmitted to macaque monkeys [194]. This recent study [194] belongs to a series of investigations that were initiated to evaluate the potential for transmission of atypical BSE to humans using experimental studies in non-human primates and in transgenic mice expressing the human PrP. This question was first raised following the initial discovery of BASE in Italy, which revealed certain molecular and lesional similarities to a sub-type of sporadic CJD (M/V Type 2) [65]. In another study, some molecular similarities were also emphasized regarding the identification of comparable C-terminally cleaved PrPSc products in both H-type BSE in cattle and in some CJD cases in humans [189]. This was recently reinforced by the observations that the amounts of the 13-kDa C-terminal fragment were specifically increased in CJD Type 1 cases, but this fragment was virtually undetectable in variant CJD and in most sporadic CJD subtypes associated with Type 2 (except the MM2 thalamic sub-type) [195]. While H-type BSE and L-type BSE are already strongly reminiscent of molecular Types 1 and 2, respectively, in sporadic CJD, these observations rather suggest that both cattle and humans could be affected by diseases involving similar molecular mechanisms. However, given the enigmatic origin of such diseases, it is obviously important to investigate any possible causal link between these human and bovine diseases.

In this context, successful transmission of L-type BSE has been reported in a cynomolgus macaque monkey inoculated by the intra-cerebral route. This infection was characterized by a shorter survival period (26 months with 25 mg cattle brain inoculated) than in monkeys infected with classical BSE (40 months with 100 mg cattle brain inoculated), and distinctive clinical, neuropathological, and biochemical features were recorded [194]. Molecular similarities with a rare MM2 cortical subtype of sCJD in humans were also observed, rather than with the MV2 subtype. Transmission of L-type BSE has also been demonstrated by the intra-cerebral route in a transgenic mouse line expressing normal levels of the human M129 PrP protein, and a higher (60%) transmission rate than that observed with classical BSE was reported [196]. Similar conclusions were reached from another study using another transgenic mouse line that over-expresses (about sixfold) M129 human PrP [186]. This study also concluded that there is no significant species barrier for L-type BSE between cattle and humans, as an attack rate of 100% was observed, and the incubation time was not reduced upon secondary passage. In contrast, transmission of the classical BSE agent to the same mice showed a substantial species barrier effect.

snip...

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

Thursday, August 12, 2010

Seven main threats for the future linked to prions

First threat

The TSE road map defining the evolution of European policy for protection against prion diseases is based on a certain numbers of hypotheses some of which may turn out to be erroneous. In particular, a form of BSE (called atypical Bovine Spongiform Encephalopathy), recently identified by systematic testing in aged cattle without clinical signs, may be the origin of classical BSE and thus potentially constitute a reservoir, which may be impossible to eradicate if a sporadic origin is confirmed.

***Also, a link is suspected between atypical BSE and some apparently sporadic cases of Creutzfeldt-Jakob disease in humans. These atypical BSE cases constitute an unforeseen first threat that could sharply modify the European approach to prion diseases.

Second threat

snip...

http://www.neuroprion.org/en/np-neuroprion.html

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

http://prionpathy.blogspot.com/

Rural and Regional Affairs and Transport References Committee

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

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

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

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

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...TSS)

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

Wednesday, March 9, 2011

27 U.S. Senators want to force feed Japan Highly Potential North America Mad Cow Beef TSE PRION CJD

March 8, 2011

President Barack Obama The White House

1600 Pennsylvania Avenue, W Washington, DC 20500

Dear President Obama:

http://transmissiblespongiformencephalopathy.blogspot.com/2011/03/27-us-senators-want-to-force-feed-japan.html

http://madcowtesting.blogspot.com/

Friday, May 13,

2011 EFSA Joint Scientific Opinion on any possible epidemiological or molecular association between TSEs in animals and humans

http://transmissiblespongiformencephalopathy.blogspot.com/2011/05/efsa-joint-scientific-opinion-on-any.html

Sunday, May 01, 2011

STUDY OF ATYPICAL BSE 2010 Annual Report May 2011

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

In addition, non-human primates are specifically susceptible for atypical BSE as demonstrated by an approximately 50% shortened incubation time for L-type BSE as compared to C-type. Considering the current scientific information available, it cannot be assumed that these different BSE types pose the same human health risks as C-type BSE or that these risks are mitigated by the same protective measures.

This study will contribute to a correct definition of specified risk material (SRM) in atypical BSE. The incumbent of this position will develop new and transfer existing, ultra-sensitive methods for the detection of atypical BSE in tissue of experimentally infected cattle.

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

Tuesday, November 02, 2010

BSE - ATYPICAL LESION DISTRIBUTION (RBSE 92-21367) statutory (obex only) diagnostic criteria CVL 1992

http://bse-atypical.blogspot.com/2010/11/bse-atypical-lesion-distribution-rbse.html

let's take a closer look at this new prionpathy or prionopathy, and then let's look at the g-h-BSEalabama mad cow.

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

ALABAMA MAD COW g-h-BSEalabama

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

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

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

her healthy calf also carried the mutation (J. A. Richt and S. M. Hall PLoS Pathog. 4, e1000156; 2008).

This raises the possibility that the disease could occasionally be genetic in origin. Indeed, the report of the UK BSE Inquiry in 2000 suggested that the UK epidemic had most likely originated from such a mutation and argued against the scrapierelated assumption. Such rare potential pathogenic PRNP mutations could occur in countries at present considered to be free of BSE, such as Australia and New Zealand. So it is important to maintain strict surveillance for BSE in cattle, with rigorous enforcement of the ruminant feed ban (many countries still feed ruminant proteins to pigs). Removal of specified risk material, such as brain and spinal cord, from cattle at slaughter prevents infected material from entering the human food chain. Routine genetic screening of cattle for PRNP mutations, which is now available, could provide additional data on the risk to the public. Because the point mutation identified in the Alabama animals is identical to that responsible for the commonest type of familial (genetic) CJD in humans, it is possible that the resulting infective prion protein might cross the bovine–human species barrier more easily. Patients with vCJD continue to be identified. The fact that this is happening less often should not lead to relaxation of the controls necessary to prevent future outbreaks.

Malcolm A. Ferguson-Smith Cambridge University Department of Veterinary Medicine, Madingley Road, Cambridge CB3 0ES, UK e-mail: maf12@cam.ac.uk Jürgen A. Richt College of Veterinary Medicine, Kansas State University, K224B Mosier Hall, Manhattan, Kansas 66506-5601, USA

NATURE|Vol 457|26 February 2009

http://www.nature.com/nature/journal/v457/n7233/full/4571079b.html

Monday, May 11, 2009

Rare BSE mutation raises concerns over risks to public health

http://bse-atypical.blogspot.com/2009/05/rare-bse-mutation-raises-concerns-over.html

Saturday, August 14, 2010

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

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

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

Saturday, June 12, 2010

PUBLICATION REQUEST AND FOIA REQUEST Project Number: 3625-32000-086-05 Study of Atypical Bse

http://bse-atypical.blogspot.com/2010/06/publication-request-and-foia-request.html

Wednesday, July 28, 2010

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

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

P.9.21

Molecular characterization of BSE in Canada

Jianmin Yang1, Sandor Dudas2, Catherine Graham2, Markus Czub3, Tim McAllister1, Stefanie Czub1 1Agriculture and Agri-Food Canada Research Centre, Canada; 2National and OIE BSE Reference Laboratory, Canada; 3University of Calgary, Canada

Background: Three BSE types (classical and two atypical) have been identified on the basis of molecular characteristics of the misfolded protein associated with the disease. To date, each of these three types have been detected in Canadian cattle.

Objectives: This study was conducted to further characterize the 16 Canadian BSE cases based on the biochemical properties of there associated PrPres. Methods: Immuno-reactivity, molecular weight, glycoform profiles and relative proteinase K sensitivity of the PrPres from each of the 16 confirmed Canadian BSE cases was determined using modified Western blot analysis.

Results: Fourteen of the 16 Canadian BSE cases were C type, 1 was H type and 1 was L type. The Canadian H and L-type BSE cases exhibited size shifts and changes in glycosylation similar to other atypical BSE cases. PK digestion under mild and stringent conditions revealed a reduced protease resistance of the atypical cases compared to the C-type cases. N terminal- specific antibodies bound to PrPres from H type but not from C or L type. The C-terminal-specific antibodies resulted in a shift in the glycoform profile and detected a fourth band in the Canadian H-type BSE.

Discussion: The C, L and H type BSE cases in Canada exhibit molecular characteristics similar to those described for classical and atypical BSE cases from Europe and Japan. This supports the theory that the importation of BSE contaminated feedstuff is the source of C-type BSE in Canada. *It also suggests a similar cause or source for atypical BSE in these countries.

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

Discussion: The C, L and H type BSE cases in Canada exhibit molecular characteristics similar to those described for classical and atypical BSE cases from Europe and Japan. This supports the theory that the importation of BSE contaminated feedstuff is the source of C-type BSE in Canada. *It also suggests a similar cause or source for atypical BSE in these countries.

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

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

Archive Number 20101206.4364 Published Date 06-DEC-2010 Subject PRO/AH/EDR> Prion disease update 2010 (11)

PRION DISEASE UPDATE 2010 (11)

SEE;

TAFS1 Position Paper on Position Paper on Relaxation of the Feed Ban in the EU Berne, 2010 TAFS

INTERNATIONAL FORUM FOR TRANSMISSIBLE ANIMAL DISEASES AND FOOD SAFETY a non-profit Swiss Foundation

http://www.promedmail.org/pls/apex/f?p=2400:1001:5492868805159684::NO::F2400_P1001_BACK_PAGE,F2400_P1001_PUB_MAIL_ID:1000,86129

Saturday, November 6, 2010

TAFS1 Position Paper on Position Paper on Relaxation of the Feed Ban in the EU Berne, 2010 TAFS

INTERNATIONAL FORUM FOR TRANSMISSIBLE ANIMAL DISEASES AND FOOD SAFETY a non-profit S wiss Foundation

http://madcowfeed.blogspot.com/2010/11/tafs1-position-paper-on-position-paper.html

http://www.aphis.usda.gov/import_export/plants/manuals/ports/downloads/apm_pdf/03_18petfoodsandfeed.pdf

http://www.dardni.gov.uk/index/animal-health/animal-diseases/bse/bse-feed-ban.htm

"Blood meal used to make cattle feed was recalled because it was cross- contaminated with prohibited bovine meat and bone meal that had been manufactured on common equipment and labeling did not bear cautionary BSE statement."

10,000,000+ LBS. of PROHIBITED BANNED MAD COW FEED I.E. BLOOD LACED MBM IN COMMERCE USA 2007

Date: March 21, 2007 at 2:27 pm PST

RECALLS AND FIELD CORRECTIONS: VETERINARY MEDICINES -- CLASS II

___________________________________

PRODUCT

Bulk cattle feed made with recalled Darling's 85% Blood Meal, Flash Dried, Recall # V-024-2007

CODE

Cattle feed delivered between 01/12/2007 and 01/26/2007

RECALLING FIRM/MANUFACTURER

Pfeiffer, Arno, Inc, Greenbush, WI. by conversation on February 5, 2007.

Firm initiated recall is ongoing.

REASON

Blood meal used to make cattle feed was recalled because it was cross- contaminated with prohibited bovine meat and bone meal that had been manufactured on common equipment and labeling did not bear cautionary BSE statement.

VOLUME OF PRODUCT IN COMMERCE

42,090 lbs.

DISTRIBUTION

WI

___________________________________

PRODUCT

Custom dairy premix products: MNM ALL PURPOSE Pellet, HILLSIDE/CDL Prot- Buffer Meal, LEE, M.-CLOSE UP PX Pellet, HIGH DESERT/ GHC LACT Meal, TATARKA, M CUST PROT Meal, SUNRIDGE/CDL PROTEIN Blend, LOURENZO, K PVM DAIRY Meal, DOUBLE B DAIRY/GHC LAC Mineral, WEST PIONT/GHC CLOSEUP Mineral, WEST POINT/GHC LACT Meal, JENKS, J/COMPASS PROTEIN Meal, COPPINI - 8# SPECIAL DAIRY Mix, GULICK, L-LACT Meal (Bulk), TRIPLE J - PROTEIN/LACTATION, ROCK CREEK/GHC MILK Mineral, BETTENCOURT/GHC S.SIDE MK-MN, BETTENCOURT #1/GHC MILK MINR, V&C DAIRY/GHC LACT Meal, VEENSTRA, F/GHC LACT Meal, SMUTNY, A- BYPASS ML W/SMARTA, Recall # V-025-2007

CODE

The firm does not utilize a code - only shipping documentation with commodity and weights identified.

RECALLING FIRM/MANUFACTURER

Rangen, Inc, Buhl, ID, by letters on February 13 and 14, 2007. Firm initiated recall is complete.

REASON

Products manufactured from bulk feed containing blood meal that was cross contaminated with prohibited meat and bone meal and the labeling did not bear cautionary BSE statement.

VOLUME OF PRODUCT IN COMMERCE

9,997,976 lbs.

DISTRIBUTION

ID and NV

END OF ENFORCEMENT REPORT FOR MARCH 21, 2007

http://www.fda.gov/Safety/Recalls/EnforcementReports/2007/ucm120446.htm

Tuesday, May 3, 2011

PRION, TSE, typical, atypical BSE, aka mad cow disease, spray dried blood, feed, and a recipe for disaster

http://transmissiblespongiformencephalopathy.blogspot.com/2011/05/prion-tse-typical-atypical-bse-aka-mad.html

Tuesday, September 14, 2010

Transmissible Spongiform Encephalopathies Advisory Committee; Notice of Meeting October 28 and 29, 2010 (COMMENT SUBMISSION)

http://tseac.blogspot.com/2010/09/transmissible-spongiform_14.html

Sunday, May 10, 2009

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

TO : william.freas@fda.hhs.gov

May 8, 2009

Greetings again Dr. Freas, TSEAC et al,

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

In response to the Washington State case, we announced in January, 2004 our intention to strengthen the >97 feed ban by banning the use of blood products, poultry litter and plate waste, and this was one of the changes in the plan.

*** ALICE

We did not follow through with this set of measures.

After considering the recommendations of the international review PAPER MILL REPORTING 301 495-5831 263 team we, instead, published an advance notice of proposed rule-making in July, 2004 jointly with USDA. In that proposal we tentatively proposed to ban SRMs from all animal feed. What we actually proposed in October, 2005 was a partial SRM ban, limited to brain and spinal cord tissues. It took us until April 25, 2008 to finalize the proposal because we significantly underestimated the costs associated with the measures. Also, commensurate with USDA’s surveillance results and prevalence estimates, and the high level of compliance with our >97 rule, we modified the rule to apply only to brains and spinal cords from cattle 30 months of age and older, rather than cattle of all ages.

http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/BloodVaccinesandOtherBiologics/TransmissibleSpongiformEncephalopathiesAdvisoryCommittee/UCM171810.pdf

(Response) FDA agrees that the prevalence of BSE in the United States is very low, and that compliance with the current feed ban by the U.S. animal feed industry is at a high level...

http://www.fda.gov/OHRMS/DOCKETS/98fr/08-1180.pdf

suppressed peer review of Harvard study October 31, 2002

http://www.fsis.usda.gov/oa/topics/BSE_Peer_Review.pdf

Harvard Risk Assessment of Bovine Spongiform Encephalopathy Update, October 31, 2005 INTRODUCTION The United States Department of Agriculture’s Food Safety and Inspection Service (FSIS) held a public meeting on July 25, 2006 in Washington, D.C. to present findings from the Harvard Risk Assessment of Bovine Spongiform Encephalopathy Update, October 31, 2005 (report and model located on the FSIS website: http://www.fsis.usda.gov/Science/Risk_Assessments/index.asp).

Comments on technical aspects of the risk assessment were then submitted to FSIS. Comments were received from Food and Water Watch, Food Animal Concerns Trust (FACT), Farm Sanctuary, R-CALF USA, Linda A Detwiler, and Terry S. Singeltary.

This document provides itemized replies to the public comments received on the 2005 updated Harvard BSE risk assessment. Please bear the following points in mind:

http://www.fsis.usda.gov/PDF/BSE_Risk_Assess_Response_Public_Comments.pdf

Monday, April 25, 2011

Experimental Oral Transmission of Atypical Scrapie to Sheep

Volume 17, Number 5–May 2011

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

putting the cart before the horse OIE TSE policy. ...TSS

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

Published online 11 February 2011 | Nature | doi:10.1038/news.2011.87

News

Livestock plagues are spreading As farming intensifies, researchers warn that the developing world is "dangerously behind" on controlling animal diseases.

Natasha Gilbert

http://www.nature.com/news/2011/110211/full/news.2011.87.html

Friday, February 11, 2011

Atypical/Nor98 Scrapie Infectivity in Sheep Peripheral Tissues

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

Friday, February 04, 2011

NMLB and USDA allow scrapie prion infected mutton to enter food chain on the Navajo Reservation in New Mexico

http://scrapie-usa.blogspot.com/2011/02/nmlb-and-usda-allow-scrapie-prion.html

Sunday, December 12, 2010

EFSA reviews BSE/TSE infectivity in small ruminant tissues News Story 2 December 2010

http://transmissiblespongiformencephalopathy.blogspot.com/2010/12/efsa-reviews-bsetse-infectivity-in.html

Thursday, December 23, 2010

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

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

Thursday, November 18, 2010

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

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

Sunday, October 3, 2010

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

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

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

Sunday, March 27, 2011

SCRAPIE USA UPDATE FEBRUARY 2011

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

Wednesday, February 16, 2011

IN CONFIDENCE

SCRAPIE TRANSMISSION TO CHIMPANZEES

IN CONFIDENCE

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

Sunday, April 18, 2010

SCRAPIE AND ATYPICAL SCRAPIE TRANSMISSION STUDIES A REVIEW 2010

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

Wednesday, January 19, 2011

EFSA and ECDC review scientific evidence on possible links between TSEs in animals and humans Webnachricht 19 Januar 2011

http://transmissiblespongiformencephalopathy.blogspot.com/2011/01/efsa-and-ecdc-review-scientific.html

Tuesday, January 18, 2011

Agent strain variation in human prion disease: insights from a molecular and pathological review of the National Institutes of Health series of experimentally transmitted disease

http://transmissiblespongiformencephalopathy.blogspot.com/2011/01/agent-strain-variation-in-human-prion.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

UPDATED DATA ON 2ND CWD STRAIN

Wednesday, September 08, 2010

CWD PRION CONGRESS SEPTEMBER 8-11 2010

http://chronic-wasting-disease.blogspot.com/2010/09/cwd-prion-2010.html

Thursday, April 28, 2011

Chronic Wasting Disease Testing and Prevalence Wisconsin April 2011

http://chronic-wasting-disease.blogspot.com/2011/04/chronic-wasting-disease-testing-and.html

Wednesday, January 5, 2011

ENLARGING SPECTRUM OF PRION-LIKE DISEASES Prusiner Colby et al 2011

Prions

David W. Colby1,* and Stanley B. Prusiner1,2

http://betaamyloidcjd.blogspot.com/2011/01/enlarging-spectrum-of-prion-like.html

Creutzfeldt Jakob Disease (s)

Variably Protease-Sensitive Prionopathy: a Novel Disease of the Prion Protein 17 May 2011

Wednesday, May 18, 2011

Variably Protease-Sensitive Prionopathy: a Novel Disease of the Prion Protein 17 May 2011 Journal of Molecular Neuroscience DOI: 10.1007/s12031-011-9543-1

snip...

Innoduction

In 2008, we reported 11 cases affected by a disease that differed from typical human prion diseases such as sporadic and familial Creutzfeldt-Jakob diseae (CJD) clinically, pathologically, and more importantly for the characteristics of the abnormal, disease-related prion protein (PrPDis) present in the brain of the cases (Gambetti et al. 2008). A striking feature of the PrPDis was the apparent lack of resistance to treatment with proteases as opposed to the protease resistance that is a prominent feature of atypical prion diseases.

Another striking feature of these cases was the genotype of the prion protein (PrP) gene which is characterized by a common methionine (Met)/valine (Val) polymorphism at codon 129 (Collinge et al. 1991). All the 11 cases were homozygous for Val at codon 129 of the PrP gene although the prevalence of this PrP genotype in the general Caueasian population is approximately 12% (Collinge et al. 1991).

Furthermore, none of the cases had a mutation in the open reading frame (ORF) of the PrP gene where all the known mutation have been found (Kong et al, 2004) although six of the ten informative cases had family history of dementia.

In 2010. we reported 15 new case affected by a condition similar to that previously described for clinical and histopathological features as well as for the characteristics of the abnormal prion protein, but these cases included not only patients who were homozygous Val at codon 129 of the PrP gene like the previous ones but also cases that were homozygous Met (Met/Met) and heterozygous (Met/Val) (Zou et al. 2010a). Because the 129 Met/Met and Metl/Val cases PrPDis presented less and disimilar senitivity to protease digestion, the condition was renamed variably protease-sensitive prionopathy or VPSPr.

Currently, a total of 30 cases of VPSPr have been publihed (Head et al. 2009, 2010; Jansen et al. 20I0; Rodriguez-Martinez et al. 2010; Zou et al. 2010a). These 30 cases are not equally distributed among the three 129 genotypes: 19 are Val/Val, 8 are Met/Val, and 3 are Met/Met. These findings prompt three considerations. ...

http://resources.metapress.com/pdf-preview.axd?code=f727n82052425wv0&size=largest

DEEP THROAT TO TSS 2000-2001 (take these old snips of emails with how ever many grains of salt you wish. ...tss)

The most frightening thing I have read all day is the report of Gambetti's finding of a new strain of sporadic cjd in young people...Dear God, what in the name of all that is holy is that!!! If the US has different strains of scrapie.....why????than the UK...then would the same mechanisms that make different strains of scrapie here make different strains of BSE...if the patterns are different in sheep and mice for scrapie.....could not the BSE be different in the cattle, in the mink, in the humans.......I really think the slides or tissues and everything from these young people with the new strain of sporadic cjd should be put up to be analyzed by many, many experts in cjd........bse.....scrapie Scrape the damn slide and put it into mice.....wait.....chop up the mouse brain and and spinal cord........put into some more mice.....dammit amplify the thing and start the damned research.....This is NOT rocket science...we need to use what we know and get off our butts and move....the whining about how long everything takes.....well it takes a whole lot longer if you whine for a year and then start the research!!! Not sure where I read this but it was a recent press release or something like that: I thought I would fall out of my chair when I read about how there was no worry about infectivity from a histopath slide or tissues because they are preserved in formic acid, or formalin or formaldehyde.....for God's sake........ Ask any pathologist in the UK what the brain tissues in the formalin looks like after a year.......it is a big fat sponge...the agent continues to eat the brain ......you can't make slides anymore because the agent has never stopped........and the old slides that are stained with Hemolysin and Eosin......they get holier and holier and degenerate and continue...what you looked at 6 months ago is not there........Gambetti better be photographing every damned thing he is looking at.....

Okay, you need to know. You don't need to pass it on as nothing will come of it and there is not a damned thing anyone can do about it. Don't even hint at it as it will be denied and laughed at.......... USDA is gonna do as little as possible until there is actually a human case in the USA of the nvcjd........if you want to move this thing along and shake the earth....then we gotta get the victims families to make sure whoever is doing the autopsy is credible, trustworthy, and a saint with the courage of Joan of Arc........I am not kidding!!!! so, unless we get a human death from EXACTLY the same form with EXACTLY the same histopath lesions as seen in the UK nvcjd........forget any action........it is ALL gonna be sporadic!!!

And, if there is a case.......there is gonna be every effort to link it to international travel, international food, etc. etc. etc. etc. etc. They will go so far as to find out if a sex partner had ever traveled to the UK/europe, etc. etc. .... It is gonna be a long, lonely, dangerous twisted journey to the truth. They have all the cards, all the money, and are willing to threaten and carry out those threats....and this may be their biggest downfall...

Thanks as always for your help. (Recently had a very startling revelation from a rather senior person in government here..........knocked me out of my chair........you must keep pushing. If I was a power person....I would be demanding that there be a least a million bovine tested as soon as possible and agressively seeking this disease. The big players are coming out of the woodwork as there is money to be made!!! In short: "FIRE AT WILL"!!! for the very dumb....who's "will"! "Will be the burden to bare if there is any coverup!"

again it was said years ago and it should be taken seriously....BSE will NEVER be found in the US! As for the BSE conference call...I think you did a great service to freedom of information and making some people feign integrity...I find it scary to see that most of the "experts" are employed by the federal government or are supported on the "teat" of federal funds. A scary picture! I hope there is a confidential panel organized by the new government to really investigate this thing.

You need to watch your back........but keep picking at them.......like a buzzard to the bone...you just may get to the truth!!! (You probably have more support than you know. Too many people are afraid to show you or let anyone else know. I have heard a few things myself... you ask the questions that everyone else is too afraid to ask.)

END...TSS

Asante/Collinge et al, that BSE transmission to the 129-methionine genotype can lead to an alternate phenotype that is indistinguishable from type 2 PrPSc, the commonest _sporadic_ CJD;

Asante/Collinge et al have major findings on sporadic CJD, why in the hell is this not making big news in the USA? ($$$) the fact that with the new findings from Collinge et al, that BSE transmission to the 129-methionine genotype can lead to an alternate phenotype which is indistinguishable from type 2 PrPSc, the commonest sporadic CJD, i only ponder how many of the sporadic CJDs in the USA are tied to this alternate phenotype? these new findings are very serious, and should have a major impact on the way sporadic CJDs are now treated as opposed to the vCJD that was thought to be the only TSE tied to ingesting beef, in the medical/surgical arena. these new findings should have a major impact on the way sporadic CJD is ignored, and should now be moved to the forefront of research as with vCJD/nvCJD.

http://www.fda.gov/ohrms/dockets/ac/03/slides/3923s1_OPH.htm

2011 - Here are my considerations, and they have not changed ;

Thursday, July 10, 2008

A Novel Human Disease with Abnormal Prion Protein Sensitive to Protease update July 10, 2008

Although several subjects had family histories of dementia, no mutations were found in the PrP gene open reading frame.

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

***+++***

Thursday, July 10, 2008

A Novel Human Disease with Abnormal Prion Protein Sensitive to Protease update July 10, 2008 Friday, June 20, 2008

http://cjdmadcowbaseoct2007.blogspot.com/2008/07/novel-human-disease-with-abnormal-prion.html

Here we go folks. AS predicted. THIS JUST OUT !

Tuesday, August 03, 2010

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

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

Monday, August 9, 2010

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

snip...see full text ;

http://transmissiblespongiformencephalopathy.blogspot.com/2011/05/variably-protease-sensitive-prionopathy.html

http://prionopathy.blogspot.com/2011/05/variably-protease-sensitive-prionopathy.html

Tuesday, April 26, 2011

sporadic CJD RISING Text and figures of the latest annual report of the NCJDRSU covering the period 1990-2009 (published 11th March 2011)

http://creutzfeldt-jakob-disease.blogspot.com/2011/04/sporadic-cjd-rising-text-and-figures-of.html

Saturday, March 5, 2011

MAD COW ATYPICAL CJD PRION TSE CASES WITH CLASSIFICATIONS PENDING ON THE RISE IN NORTH AMERICA

http://transmissiblespongiformencephalopathy.blogspot.com/2011/03/mad-cow-atypical-cjd-prion-tse-cases.html

Wednesday, April 27, 2011

GENERATION ALZHEIMER'S: THE DEFINING DISEASE OF THE BABY BOOMERS

http://betaamyloidcjd.blogspot.com/2011/04/generation-alzheimers-defining-disease.html

PRION TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY PROJECTS, RESEARCH FUNDING, BSE VOLUNTARY TESTING UPDATE IN NORTH AMERICA 2011

USA PRION FUNDING 2011

"which includes the ___elimination___ of Prion activities ($5,473,000),"

All Other Emerging and Zoonotic Infectious Diseases CDC‘s FY 2012 request of $52,658,000 for all other emerging and zoonotic infectious disease activities is a decrease of $13,607,000 below the FY 2010 level, which includes the elimination of Prion activities ($5,473,000), a reduction for other cross-cutting infectious disease activities, and administrative savings. These funds support a range of critical emerging and zoonotic infectious disease programs such Lyme Disease, Chronic Fatigue Syndrome, and Special Pathogens, as well as other activities described below.

http://www.cdc.gov/fmo/topic/Budget%20Information/appropriations_budget_form_pdf/FY2012_CDC_CJ_Final.pdf

http://prionunitusaupdate2008.blogspot.com/2011/04/prion-transmissible-spongiform.html

THE PATHOLOGICAL PROTEIN

BY Philip Yam

Yam Philip Yam News Editor Scientific American www.sciam.com

Answering critics like Terry Singeltary, who feels that the U.S. under- counts CJD, Schonberger conceded that the current surveillance system has errors but stated that most of the errors will be confined to the older population.

CHAPTER 14

Laying Odds

Are prion diseases more prevalent than we thought?

Researchers and government officials badly underestimated the threat that mad cow disease posed when it first appeared in Britain. They didn't think bovine spongiform encephalopathy was a zoonosis-an animal disease that can sicken people. The 1996 news that BSE could infect humans with a new form of Creutzfeldt-Jakob disease stunned the world. It also got some biomedical researchers wondering whether sporadic CJD may really be a manifestation of a zoonotic sickness. Might it be caused by the ingestion of prions, as variant CJD is?

Revisiting Sporadic CJD

It's not hard to get Terry Singeltary going. "I have my conspiracy theories," admitted the 49-year-old Texan.1 Singeltary is probably the nation's most relentless consumer advocate when it comes to issues in prion diseases. He has helped families learn about the sickness and coordinated efforts with support groups such as CJD Voice and the CJD Foundation. He has also connected with others who are critical of the American way of handling the threat of prion diseases. Such critics include Consumers Union's Michael Hansen, journalist John Stauber, and Thomas Pringle, who used to run the voluminous www.madcow. org Web site. These three lend their expertise to newspaper and magazine stories about prion diseases, and they usually argue that prions represent more of a threat than people realize, and that the government has responded poorly to the dangers because it is more concerned about protecting the beef industry than people's health.

Singeltary has similar inclinations. ...

snip...

THE PATHOLOGICAL PROTEIN

Hardcover, 304 pages plus photos and illustrations. ISBN 0-387-95508-9

June 2003

BY Philip Yam

CHAPTER 14 LAYING ODDS

Answering critics like Terry Singeltary, who feels that the U.S. under- counts CJD, Schonberger conceded that the current surveillance system has errors but stated that most of the errors will be confined to the older population.

http://www.thepathologicalprotein.com/

http://books.google.com/books?id=ePbrQNFrHtoC&pg=PA223&lpg=PA223&dq=the+pathological+protein+laying+odds+It%E2%80%99s+not+hard+to+get+Terry+Singeltary+going&source=bl&ots=um0PFAZSZD&sig=JWaGR7M7-1WeAr2qAXq8D6J_jak&hl=en&ei=MhtjS8jMJM2ztgeFoa2iBg&sa=X&oi=book_result&ct=result&resnum=1&ved=0CAcQ6AEwAA#v=onepage&q=&f=false

http://www.springerlink.com/content/r2k2622661473336/fulltext.pdf?page=1

http://www.thepathologicalprotein.com/

http://prionunitusaupdate2008.blogspot.com/2009/04/national-prion-disease-pathology.html

Newsdesk The Lancet Infectious Diseases, Volume 3, Issue 8, Page 463, August 2003 doi:10.1016/S1473-3099(03)00715-1Cite or Link Using DOI

Tracking spongiform encephalopathies in North America

Xavier Bosch

"My name is Terry S Singeltary Sr, and I live in Bacliff, Texas. I lost my mom to hvCJD (Heidenhain variant CJD) and have been searching for answers ever since. What I have found is that we have not been told the truth. CWD in deer and elk is a small portion of a much bigger problem." 49-year-old Singeltary is one of a number of people who have remained largely unsatisfied after being told that a close relative died from a rapidly progressive dementia compatible with spontaneous Creutzfeldt-Jakob disease (CJD). So he decided to gather hundreds of documents on transmissible spongiform encephalopathies (TSE) and realised that if Britons could get variant CJD from bovine spongiform encephalopathy (BSE), Americans might get a similar disorder from chronic wasting disease (CWD)-the relative of mad cow disease seen among deer and elk in the USA. Although his feverish.

http://linkinghub.elsevier.com/retrieve/pii/S1473309903007151

http://www.thelancet.com/journals/laninf/article/PIIS1473-3099(03)00715-1/fulltext

http://www.mdconsult.com/das/article/body/180784492-2/jorg=journal&source=&sp=13979213&sid=0/N/368742/1.html?issn=14733099

Diagnosis and Reporting of Creutzfeldt-Jakob Disease Singeltary, Sr et al. JAMA.2001; 285: 733-734. Vol. 285 No. 6, February 14, 2001 JAMA

Diagnosis and Reporting of Creutzfeldt-Jakob Disease

To the Editor: In their Research Letter, Dr Gibbons and colleagues1 reported that the annual US death rate due to Creutzfeldt-Jakob disease (CJD) has been stable since 1985. These estimates, however, are based only on reported cases, and do not include misdiagnosed or preclinical cases. It seems to me that misdiagnosis alone would drastically change these figures. An unknown number of persons with a diagnosis of Alzheimer disease in fact may have CJD, although only a small number of these patients receive the postmortem examination necessary to make this diagnosis. Furthermore, only a few states have made CJD reportable. Human and animal transmissible spongiform encephalopathies should be reportable nationwide and internationally.

Terry S. Singeltary, Sr Bacliff, Tex

1. Gibbons RV, Holman RC, Belay ED, Schonberger LB. Creutzfeldt-Jakob disease in the United States: 1979-1998. JAMA. 2000;284:2322-2323. FREE FULL TEXT

http://jama.ama-assn.org/cgi/content/extract/285/6/733?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=singeltary&searchid=1&FIRSTINDEX=0&resourcetype=HWCIT

http://jama.ama-assn.org/cgi/content/full/285/6/733?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=singeltary&searchid=1&FIRSTINDEX=0&resourcetype=HWCIT

DER SPIEGEL (9/2001) - 24.02.2001 (9397 Zeichen) USA: Loch in der Mauer Die BSE-Angst erreicht Amerika: Trotz strikter Auflagen gelangte in Texas verbotenes Tiermehl ins Rinderfutter - die Kontrollen der Aufsichtsbehördensind lax.Link auf diesen Artikel im Archiv:

http://service.spiegel.de/digas/find?DID=18578755

"Löcher wie in einem Schweizer Käse" hat auch Terry Singeltary im Regelwerk der FDA ausgemacht. Der Texaner kam auf einem tragischen Umweg zu dem Thema: Nachdem seine Mutter 1997 binnen weniger Wochen an der Creutzfeldt-Jakob-Krankheit gestorben war, versuchte er, die Ursachen der Infektion aufzuspüren. Er klagte auf die Herausgabe von Regierungsdokumenten und arbeitete sich durch Fachliteratur; heute ist er überzeugt, dass seine Mutter durch die stetige Einnahme von angeblich kräftigenden Mitteln erkrankte, in denen - völlig legal - Anteile aus Rinderprodukten enthalten sind.

Von der Fachwelt wurde Singeltary lange als versponnener Außenseiter belächelt. Doch mittlerweile sorgen sich auch Experten, dass ausgerechnet diese verschreibungsfreien Wundercocktails zur Stärkung von Intelligenz, Immunsystem oder Libido von den Importbeschränkungen ausgenommen sind. Dabei enthalten die Pillen und Ampullen, die in Supermärkten verkauft werden, exotische Mixturen aus Rinderaugen; dazu Extrakte von Hypophyse oder Kälberföten, Prostata, Lymphknoten und gefriergetrocknetem Schweinemagen. In die USA hereingelassen werden auch Blut, Fett, Gelatine und Samen. Diese Stoffe tauchen noch immer in US-Produkten auf, inklusive Medizin und Kosmetika. Selbst in Impfstoffen waren möglicherweise gefährliche Rinderprodukte enthalten. Zwar fordert die FDA schon seit acht Jahren die US-Pharmaindustrie auf, keine Stoffe aus Ländern zu benutzen, in denen die Gefahr einer BSE-Infizierung besteht. Aber erst kürzlich verpflichteten sich fünf Unternehmen, darunter Branchenführer wie GlaxoSmithKline, Aventis und American Home Products, ihre Seren nur noch aus unverdächtigem Material herzustellen.

"Its as full of holes as Swiss Cheese" says Terry Singeltary of the FDA regulations. ...

http://www.spiegel.de/spiegel/print/d-18578755.html

http://wissen.spiegel.de/wissen/image/show.html?did=18578755&aref=image024/E0108/SCSP200100901440145.pdf&thumb=false

http://service.spiegel.de/digas/servlet/find/DID=18578755

Suspect symptoms

What if you can catch old-fashioned CJD by eating meat from a sheep infected with scrapie?

28 Mar 01

Like lambs to the slaughter 31 March 2001 by Debora MacKenzie Magazine issue 2284. Subscribe and get 4 free issues. 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 mice as sCJD.

"This means we cannot rule out that at least some sCJD may be caused by some strains of scrapie," says team member Jean-Philippe Deslys of the French Atomic Energy Commission's medical research laboratory in Fontenay-aux-Roses, south-west of Paris. Hans Kretschmar of the University of Göttingen, who coordinates CJD surveillance in Germany, is so concerned by the findings that he now wants to trawl back through past sCJD cases to see if any might have been caused by eating infected mutton or lamb.

Scrapie has been around for centuries and until now there has been no evidence that it poses a risk to human health. But if the French finding means that scrapie can cause sCJD in people, countries around the world may have overlooked a CJD crisis to rival that caused by BSE.

Deslys and colleagues were originally studying vCJD, not sCJD. They injected the brains of macaque monkeys with brain from BSE cattle, and from French and British vCJD patients. The brain damage and clinical symptoms in the monkeys were the same for all three. Mice injected with the original sets of brain tissue or with infected monkey brain also developed the same symptoms.

As a control experiment, the team also injected mice with brain tissue from people and animals with other prion diseases: a French case of sCJD; a French patient who caught sCJD from human-derived growth hormone; sheep with a French strain of scrapie; and mice carrying a prion derived from an American scrapie strain. As expected, they all affected the brain in a different way from BSE and vCJD. But while the American strain of scrapie caused different damage from sCJD, the French strain produced exactly the same pathology.

"The main evidence that scrapie does not affect humans has been epidemiology," says Moira Bruce of the neuropathogenesis unit of the Institute for Animal Health in Edinburgh, who was a member of the same team as Deslys. "You see about the same incidence of the disease everywhere, whether or not there are many sheep, and in countries such as New Zealand with no scrapie." In the only previous comparisons of sCJD and scrapie in mice, Bruce found they were dissimilar.

But there are more than 20 strains of scrapie, and six of sCJD. "You would not necessarily see a relationship between the two with epidemiology if only some strains affect only some people," says Deslys. Bruce is cautious about the mouse results, but agrees they require further investigation. Other trials of scrapie and sCJD in mice, she says, are in progress.

People can have three different genetic variations of the human prion protein, and each type of protein can fold up two different ways. Kretschmar has found that these six combinations correspond to six clinical types of sCJD: each type of normal prion produces a particular pathology when it spontaneously deforms to produce sCJD.

But if these proteins deform because of infection with a disease-causing prion, the relationship between pathology and prion type should be different, as it is in vCJD. "If we look at brain samples from sporadic CJD cases and find some that do not fit the pattern," says Kretschmar, "that could mean they were caused by infection."

There are 250 deaths per year from sCJD in the US, and a similar incidence elsewhere. Singeltary and other US activists think that some of these people died after eating contaminated meat or "nutritional" pills containing dried animal brain. Governments will have a hard time facing activists like Singeltary if it turns out that some sCJD isn't as spontaneous as doctors have insisted.

Deslys's work on macaques also provides further proof that the human disease vCJD is caused by BSE. And the experiments showed that vCJD is much more virulent to primates than BSE, even when injected into the bloodstream rather than the brain. This, says Deslys, means that there is an even bigger risk than we thought that vCJD can be passed from one patient to another through contaminated blood transfusions and surgical instruments.

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

2 January 2000

British Medical Journal

U.S. Scientist should be concerned with a CJD epidemic in the U.S., as well

http://www.bmj.com/cgi/eletters/320/7226/8/b#6117

15 November 1999

British Medical Journal

vCJD in the USA * BSE in U.S.

http://www.bmj.com/cgi/eletters/319/7220/1312/b#5406

2006

USA sporadic CJD cases rising ;

There is a growing number of human CJD cases, and they were presented last week in San Francisco by Luigi Gambatti(?) from his CJD surveillance collection.

He estimates that it may be up to 14 or 15 persons which display selectively SPRPSC and practically no detected RPRPSC proteins.

http://www.fda.gov/ohrms/dockets/ac/06/transcripts/1006-4240t1.htm

http://www.fda.gov/ohrms/dockets/ac/06/transcripts/2006-4240t1.pdf

2008

The statistical incidence of CJD cases in the United States has been revised to reflect that there is one case per 9000 in adults age 55 and older. Eighty-five percent of the cases are sporadic, meaning there is no known cause at present.

http://www.cjdfoundation.org/fact.html

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

Saturday, January 2, 2010

Human Prion Diseases in the United States January 1, 2010 ***FINAL***

http://prionunitusaupdate2008.blogspot.com/2010/01/human-prion-diseases-in-united-states.html

Manuscript Draft Manuscript Number: Title: HUMAN and ANIMAL TSE Classifications i.e. mad cow disease and the UKBSEnvCJD only theory Article Type: Personal View Corresponding Author: Mr. Terry S. Singeltary, Corresponding Author's Institution: na First Author: Terry S Singeltary, none Order of Authors: Terry S Singeltary, none; Terry S. Singeltary Abstract: TSEs have been rampant in the USA for decades in many species, and they all have been rendered and fed back to animals for human/animal consumption. I propose that the current diagnostic criteria for human TSEs only enhances and helps the spreading of human TSE from the continued belief of the UKBSEnvCJD only theory in 2007.

http://www.regulations.gov/fdmspublic/ContentViewer?objectId=090000648027c28e&disposition=attachment&contentType=pdf

my comments to PLosone here ;

http://www.plosone.org/annotation/listThread.action?inReplyTo=info%3Adoi%2F10.1371%2Fannotation%2F04ce2b24-613d-46e6-9802-4131e2bfa6fd&root=info%3Adoi%2F10.1371%2Fannotation%2F04ce2b24-613d-46e6-9802-4131e2bfa6fd

Monday, May 23, 2011

CDC Assesses Potential Human Exposure to Prion Diseases Travel Warning

http://transmissiblespongiformencephalopathy.blogspot.com/2011/05/cdc-assesses-potential-human-exposure.html

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

STUDY OF ATYPICAL BSE 2010 Annual Report May 2011

2011-05-01T16:40:00.000-07:00

Research Project: STUDY OF ATYPICAL BSE Location: Virus and Prion Research Unit

2010 Annual Report

1a.Objectives (from AD-416) The objective of this cooperative research project with Dr. Maria Caramelli from the Italian BSE Reference Laboratory in Turin, Italy, is to conduct comparative studies with the U.S. bovine spongiform encephalopathy (BSE) isolate and the atypical BSE isolates identified in Italy. The studies will cover the following areas: 1. Evaluation of present diagnostics tools used in the U.S. for the detection of atypical BSE cases. 2. Molecular comparison of the U.S. BSE isolate and other typical BSE isolates with atypical BSE cases. 3. Studies on transmissibility and tissue distribution of atypical BSE isolates in cattle and other species.

1b.Approach (from AD-416) This project will be done as a Specific Cooperative Agreement with the Italian BSE Reference Laboratory, Istituto Zooprofilattico Sperimentale del Piemonte, in Turin, Italy. It is essential for the U.S. BSE surveillance program to analyze the effectiveness of the U.S diagnostic tools for detection of atypical cases of BSE. Molecular comparisons of the U.S. BSE isolate with atypical BSE isolates will provide further characterization of the U.S. BSE isolate. Transmission studies are already underway using brain homogenates from atypical BSE cases into mice, cattle and sheep. It will be critical to see whether the atypical BSE isolates behave similarly to typical BSE isolates in terms of transmissibility and disease pathogenesis. If transmission occurs, tissue distribution comparisons will be made between cattle infected with the atypical BSE isolate and the U.S. BSE isolate. Differences in tissue distribution could require new regulations regarding specific risk material (SRM) removal.

3.Progress Report This report documents research conducted under a Specific Cooperative Agreement between ARS and the IST ZOOPROFIL SPERIMENT PIEMONTE. Additional details for the research can be found in the report for the parent project 3625-32000-086-00D, TRANSMISSION, DIFFERENTIATION, AND PATHOBIOLOGY OF TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES

The aim of the cooperative research project was to: 1. Evaluate present diagnostic tools used in the U.S. for the detection of atypical bovine spongiform encephalopathy (BSE) cases. 2. Perform molecular comparison of the U.S. BSE isolate and other typical BSE isolates with atypical BSE cases. 3. Support studies on transmissibility and tissue distribution of atypical BSE isolates in cattle and other species. To complete objectives 1 and 2 (i.e., to compare Italian and U.S. BSE confirmatory protocols for detection of classical (C-) and atypical (H- and L-type) BSE cases), samples of Italian C-BSE and Italian L-type BSE (BASE), both frozen and formalin fixed, were sent to USDA laboratories in Ames, Iowa, to undergo Western blot (WB) and immunohistochemistry (IHC) comparison studies for PrPSc detection according to U.S. and Italian methods. A Western blot expert from the cooperating Italian lab assisted ARS scientists in performing the protocols from each laboratory in parallel. A comparative IHC study between U.S. and Italian BSE confirmatory protocols was also performed when the collaborator sent a scientist to Ames to assist in performing the Italian IHC protocol on BSE samples chosen for the study. Results obtained showed the Italian and U.S. IHC procedures were alike in PrPSc detection regarding its tissue distribution, deposition pattern and intensity of staining on all the C-, L- and H-type BSE cases considered. In addition, the U.S. protocol evidenced the characteristic presence of plaques in the frontal cortex of the Italian BASE case similar to the Italian protocol. Data from studies on objectives 1 & 2 has been presented at several international meetings in 2008 and 2009, and has been finalized into manuscript form for publication in a peer-reviewed journal (Journal of Veterinary Diagnostic Investigation). In support of objective 3, the cooperators completed and published their transmissibility and tissue distribution work on BASE cases in a peer-reviewed journal in 2008 (PLoS Pathogens Volume 4, page e1000075). They reported that in all experimentally infected atypical BSE animals, no PrPSc was detected in peripheral tissues either by standard Western blot analysis or following phosphotungstic acid precipitation. Peripheral issues examined included cervical and mesenteric lymph nodes, spleen, thymus, liver, lung, peripheral nerves, and forelimb and hind limb muscles. These findings support the conclusion there is no scientific evidence to expand the list of tissues included in the Specified Risk Material ban based on atypical BSE research data, thus confirming other studies indicating the pathogenesis of BSE in cattle is fundamentally different from that in sheep and mice, due to an exclusive intraneuronal spread of infectivity from the gut to the central nervous system. Methods used for monitoring included email, site visits, and periodic written reports.

http://www.ars.usda.gov/research/projects/projects.htm?ACCN_NO=408490&showpars=true&fy=2010

============================================

They reported that in all experimentally infected atypical BSE animals, no PrPSc was detected in peripheral tissues either by standard Western blot analysis or following phosphotungstic acid precipitation. Peripheral issues examined included cervical and mesenteric lymph nodes, spleen, thymus, liver, lung, peripheral nerves, and forelimb and hind limb muscles. These findings support the conclusion there is no scientific evidence to expand the list of tissues included in the Specified Risk Material ban based on atypical BSE research data, thus confirming other studies indicating the pathogenesis of BSE in cattle is fundamentally different from that in sheep and mice, due to an exclusive intraneuronal spread of infectivity from the gut to the central nervous system. Methods used for monitoring included email, site visits, and periodic written reports.

=============================================

Saturday, June 12, 2010

PUBLICATION REQUEST AND FOIA REQUEST Project Number: 3625-32000-086-05 Study of Atypical Bse

http://bse-atypical.blogspot.com/2010/06/publication-request-and-foia-request.html

Wednesday, July 28, 2010

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

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

Thursday, June 24, 2010

Accumulation of L-type Bovine Prions in Peripheral Nerve Tissues Volume 16, Number 7–July 2010

Dispatch

Accumulation of L-type Bovine Prions in Peripheral Nerve Tissues

Yoshifumi Iwamaru, Morikazu Imamura, Yuichi Matsuura, Kentaro Masujin, Yoshihisa Shimizu, Yujing Shu, Megumi Kurachi, Kazuo Kasai, Yuichi Murayama, Shigeo Fukuda, Sadao Onoe, Ken'ichi Hagiwara, Yoshio Yamakawa, Tetsutaro Sata, Shirou Mohri, Hiroyuki Okada, and Takashi Yokoyama Author affiliations: National Institute of Animal Health, Tsukuba, Ibaraki, Japan (Y. Iwamaru, M. Imamura, Y. Matsuura, K. Masujin, Y. Shimizu, Y. Shu, M. Kurachi, K. Kasai, Y. Murayama, S. Mohri, H. Okada, T. Yokoyama); Hokkaido Animal Research Center, Hokkaido, Japan (S. Fukuda, S. Onoe); and National Institute of Infectious Diseases, Tokyo, Japan (K. Hagiwara, Y. Yamakawa, T. Sata)

Suggested citation for this article

Abstract We recently reported the intraspecies transmission of L-type atypical bovine spongiform encephalopathy (BSE). To clarify the peripheral pathogenesis of L-type BSE, we studied prion distribution in nerve and lymphoid tissues obtained from experimentally challenged cattle. As with classical BSE prions, L-type BSE prions accumulated in central and peripheral nerve tissues.

Bovine spongiform encephalopathy (BSE) is a fatal neurodegenerative disorder of cattle characterized by accumulation of a protease-resistant form of a normal cellular prion protein (PrPres) in the central nervous system. The scientific literature in general has assumed that BSE in cattle is caused by a uniform strain (classical BSE). However, different neuropathologic and molecular phenotypes of BSE (atypical BSEs) have recently been reported from various countries (1). Recent data from Western blot analyses of field cases of atypical BSEs are characterized by a higher (H-type BSE) or lower (L-type BSE) molecular mass of the unglycosylated form of PrPres than is classical BSE (2). The origins of atypical BSEs remain obscure; unlike classical BSE, atypical BSE has been detected mainly in aged cattle and suggested a as possible sporadic form of BSE (3).

Several lines of evidence demonstrate that classical BSE and a variant form of Creutzfeldt-Jacob disease are most likely caused by the same agent (4,5). Transmission of classical BSE to humans has been proposed to result from ingestion of contaminated food. Whether atypical BSEs are transmissible to humans remains uncertain; however, human susceptibility to L-type BSEs is suggested by recent experimental transmission in primates (6) and mice transgenic for human prion protein (PrP) (7) by using the most effective route of intracerebral inoculations of prions. The L-type BSE prion is much more virulent in primates and in humanized mice than is the classical BSE prion, which suggests the possibility of zoonotic risk associated with the L-type BSE prion. These findings emphasize the critical importance of understanding tissue distribution of L-type BSE prions in cattle because, among the current administrative measures for BSE controls, the specified risk materials removal policy plays a crucial role in consumer protection.

In Japan, atypical BSE was detected in an aged Japanese Black cow (BSE/JP24) (8). We recently reported the successful transmission of BSE/JP24 prions to cattle and showed that the characteristics of these prions closely resemble those of L-type BSE prions found in Italy (9). In this study, we report the peripheral distribution of L-type BSE prions in experimentally challenged cattle.

The Study

snip...

Conclusions We report accumulation of L-type atypical BSE prions in peripheral nerve tissues sampled from intracerebrally challenged cattle. Our study demonstrated that almost all of the peripheral nerve tissues tested became PrPres positive in a time-dependent manner, whereas no PrPres was detectable in lymphoid tissues, even in cattle with fatal atypical BSE. Our results suggest the possibility that, like classical BSE prions, L-type BSE prions propagated in the central nervous system and were spread centrifugally by nerve pathways (11,12). In Italy, L-type BSE prions have been characterized in detail by using cattle challenged intracerebrally. However, PrPres was not detected in their peripheral tissues, including the peripheral nerves (13). The reason for the discrepancy in PrPres detection is unclear. In view of the similarities between the L-type and BSE/JP24 prion characteristics (9), this discrepancy may result from differences in the methods used for PrPres detection.

We detected infectivity in the nerve tissue samples (including samples from the obex, sciatic nerve, adrenal gland, brachial nerve plexus, and vagus nerve) obtained 10, 12, and 16 mpi. On the basis of the incubation time of 223 ± 25 (mean ± SD) days in mice injected with a 1,000-fold dilution of the obex homogenate, infectious titers in peripheral nerve tissues appeared to be 1,000 × lower than those estimated in the obex during endpoint titration of infectivity.

Our results demonstrate that L-type atypical BSE prions can be distributed in the peripheral nerve tissues of intracerebrally challenged cattle. These findings are useful for understanding L-type BSE pathogenesis and accurately assessing the risks associated with this disease. Investigations of prion distribution in cattle that have been orally challenged with L-type BSE prions are critical.

full text ;

http://www.cdc.gov/eid/content/16/7/pdfs/1151.pdf

http://www.cdc.gov/eid/content/16/7/1151.htm

Originally published as JGV in Press, 10.1099/vir.0.025387-0 on October 13, 2010 J Gen Virol 92 (2011), 467-476; DOI 10.1099/vir.0.025387-0

BSE infectivity in the absence of detectable PrPSc accumulation in the tongue and nasal mucosa of terminally diseased cattle

Anne Balkema-Buschmann, Martin Eiden, Christine Hoffmann, Martin Kaatz, Ute Ziegler, Markus Keller and Martin H. Groschup

Friedrich-Loeffler-Institut, Institute for Novel and Emerging Infectious Diseases, Südufer 10, 17493 Greifswald – Insel Riems, Germany

Correspondence Anne Balkema-Buschmann anne.buschmann@fli.bund.de

The pathogenesis of bovine spongiform encephalopathy (BSE) infections in cattle has been studied in recent years by using highly sensitive transgenic-mouse bioassays. It has been shown that in this species, the BSE agent amplifies almost exclusively in the central and peripheral nervous system. Even in animals that were killed in the clinical end stage of the disease, the lymphoreticular system was shown to be free of the infectious agent. No other animal species investigated to date exhibits such a restricted BSE-infectivity distribution pattern. However, there is growing evidence for a radial spread of infection from the central nervous system (CNS) into the periphery during the late stages of the disease. In this study, we challenged transgenic mice overexpressing the bovine prion protein with homogenates prepared from a wide variety of tissue samples collected from BSE-infected cattle. As prion infections involve the conversion of the cellular prion protein into its abnormally folded isoform (PrPSc), we applied various detection methods, such as the purification of scrapie-associated fibrils, immunohistochemistry, and the protein misfolding cyclic amplification technique. Despite negative results using these highly sensitive biochemical methods, we were, for the first time, able to detect BSE infectivity in the tongue and in the nasal mucosa of terminally diseased BSE field cases as well as experimentally challenged cattle by transgenic-mouse bioassay. This shows that BSE infectivity can be present in the peripheral tissues of terminally diseased cattle, including tissues used for human consumption.

http://vir.sgmjournals.org/cgi/content/abstract/92/2/467

Saturday, January 29, 2011

Atypical L-Type Bovine Spongiform Encephalopathy (L-BSE) Transmission to Cynomolgus Macaques, a Non-Human Primate

Jpn. J. Infect. Dis., 64 (1), 81-84, 2011

http://transmissiblespongiformencephalopathy.blogspot.com/2011/01/atypical-l-type-bovine-spongiform.html

Wednesday, March 31, 2010

Atypical BSE in Cattle

To date the OIE/WAHO assumes that the human and animal health standards set out in the BSE chapter for classical BSE (C-Type) applies to all forms of BSE which include the H-type and L-type atypical forms. This assumption is scientifically not completely justified and accumulating evidence suggests that this may in fact not be the case. Molecular characterization and the spatial distribution pattern of histopathologic lesions and immunohistochemistry (IHC) signals are used to identify and characterize atypical BSE. Both the L-type and H-type atypical cases display significant differences in the conformation and spatial accumulation of the disease associated prion protein (PrPSc) in brains of afflicted cattle. Transmission studies in bovine transgenic and wild type mouse models support that the atypical BSE types might be unique strains because they have different incubation times and lesion profiles when compared to C-type BSE.

When L-type BSE was inoculated into ovine transgenic mice and Syrian hamster the resulting molecular fingerprint had changed, either in the first or a subsequent passage, from L-type into C-type BSE. In addition, non-human primates are specifically susceptible for atypical BSE as demonstrated by an approximately 50% shortened incubation time for L-type BSE as compared to C-type. Considering the current scientific information available, it cannot be assumed that these different BSE types pose the same human health risks as C-type BSE or that these risks are mitigated by the same protective measures.

This study will contribute to a correct definition of specified risk material (SRM) in atypical BSE. The incumbent of this position will develop new and transfer existing, ultra-sensitive methods for the detection of atypical BSE in tissue of experimentally infected cattle.

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

snip...

please see all seven threats listed in the USA, and more...FULL TEXT ;

Thursday, August 12, 2010

Seven main threats for the future linked to prions

First threat

The TSE road map defining the evolution of European policy for protection against prion diseases is based on a certain numbers of hypotheses some of which may turn out to be erroneous. In particular, a form of BSE (called atypical Bovine Spongiform Encephalopathy), recently identified by systematic testing in aged cattle without clinical signs, may be the origin of classical BSE and thus potentially constitute a reservoir, which may be impossible to eradicate if a sporadic origin is confirmed. ***Also, a link is suspected between atypical BSE and some apparently sporadic cases of Creutzfeldt-Jakob disease in humans. These atypical BSE cases constitute an unforeseen first threat that could sharply modify the European approach to prion diseases.

Second threat

snip...

http://www.neuroprion.org/en/np-neuroprion.html

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

http://prionpathy.blogspot.com/

14th ICID International Scientific Exchange Brochure -

Final Abstract Number: ISE.114

Session: International Scientific Exchange

Transmissible Spongiform encephalopathy (TSE) animal and human TSE in North America

update October 2009

T. Singeltary

Bacliff, TX, USA

Background:

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.

Methods:

12 years independent research of available data

Results:

I propose that the current diagnostic criteria for human TSEs only enhances and helps the spreading of human TSE from the continued belief of the UKBSEnvCJD only theory in 2009. With all the science to date refuting it, to continue to validate this old myth, will only spread this TSE agent through a multitude of potential routes and sources i.e. consumption, medical i.e., surgical, blood, dental, endoscopy, optical, nutritional supplements, cosmetics etc.

Conclusion:

I would like to submit a review of past CJD surveillance in the USA, and the urgent need to make all human TSE in the USA a reportable disease, in every state, of every age group, and to make this mandatory immediately without further delay. The ramifications of not doing so will only allow this agent to spread further in the medical, dental, surgical arena's. Restricting the reporting of CJD and or any human TSE is NOT scientific. Iatrogenic CJD knows NO age group, TSE knows no boundaries. I propose as with Aguzzi, Asante, Collinge, Caughey, Deslys, Dormont, Gibbs, Gajdusek, Ironside, Manuelidis, Marsh, et al and many more, that the world of TSE Transmissible Spongiform Encephalopathy is far from an exact science, but there is enough proven science to date that this myth should be put to rest once and for all, and that we move forward with a new classification for human and animal TSE that would properly identify the infected species, the source species, and then the route.

http://ww2.isid.org/Downloads/14th_ICID_ISE_Abstracts.pdf

Quantification of PrPC in bovine peripheral tissues: Analysis in wild-type and PrPC-deficient cattle

Authors: Shin-Ichi Kobayashi, Yasuhisa Ano, Akikazu Sakudo, Masayoshi Yukawa, Katsuaki Sigiura, Noboru Manabe, Hiroyuki Nakayama, Takashi Onodera

Affiliations: School of Agricultural and Life Sciences, The University of Tokyo, Tokyo 113-8657, Japan

Doi: 10.3892/mmr_00000137

Pages: 561-566

Abstract: Cellular PrP (PrPC) is necessary for bovine spongiform encephalopathy (BSE) infection. The purpose of the present experiment was the quantification of PrPC in peripheral tissues to assess the risk of BSE infection from these tissues. The tissue distribution of PrPC was examined by a sandwich enzyme-linked immunosorbent assay (sELISA) and histochemical analysis. PrPC-deficient cows were used as a negative control. The sELISA revealed that the brain contained the highest PrPC content (10.7 µg/g tissue), while other organs/tissues harbored lower amounts, in decreasing order as follows: longissimus capitis muscle, iliocostalis thoracis muscle, splenius muscle, biceps femoris muscle, triceps brachii muscle, longissimus thoracis muscle, ileum, jejunum, duodenum, colon, cecum, apex linguae, omotransversarius muscle, posterior part of the corpus linguae, anterior part of the corpus linguae and radix linguae (5.2- to 31-fold less PrPC than the brain). In the tissue/organs of PrP-deficient cows, PrPC levels were under the limit of detection. Histochemical analysis showed that PrPC was expressed in nerve cells in intestinal tissues. The presence of PrPC in the bovine tongue, skeletal muscles and intestines raises the possibility of PrPSc accumulation in these tissues, indicating that these organs/tissues may serve as potential sources of BSE infection.

http://www.spandidos-publications.com/mmr/2/4/561

Atypical BSE (BASE) Transmitted from Asymptomatic Aging Cattle to a Primate

Emmanuel E. Comoy1*, Cristina Casalone2, Nathalie Lescoutra-Etchegaray1, Gianluigi Zanusso3, Sophie Freire1, Dominique Marcé1, Frédéric Auvré1, Marie-Magdeleine Ruchoux1, Sergio Ferrari3, Salvatore Monaco3, Nicole Salès4, Maria Caramelli2, Philippe Leboulch1,5, Paul Brown1, Corinne I. Lasmézas4, Jean-Philippe Deslys1

1 Institute of Emerging Diseases and Innovative Therapies, CEA, Fontenay-aux-Roses, France, 2 Istituto Zooprofilattico Sperimentale del Piemonte, Turin, Italy, 3 Policlinico G.B. Rossi, Verona, Italy, 4 Scripps Florida, Jupiter, Florida, United States of America, 5 Genetics Division, Brigham & Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America

Abstract Top Background Human variant Creutzfeldt-Jakob Disease (vCJD) results from foodborne transmission of prions from slaughtered cattle with classical Bovine Spongiform Encephalopathy (cBSE). Atypical forms of BSE, which remain mostly asymptomatic in aging cattle, were recently identified at slaughterhouses throughout Europe and North America, raising a question about human susceptibility to these new prion strains.

Methodology/Principal Findings Brain homogenates from cattle with classical BSE and atypical (BASE) infections were inoculated intracerebrally into cynomolgus monkeys (Macacca fascicularis), a non-human primate model previously demonstrated to be susceptible to the original strain of cBSE. The resulting diseases were compared in terms of clinical signs, histology and biochemistry of the abnormal prion protein (PrPres). The single monkey infected with BASE had a shorter survival, and a different clinical evolution, histopathology, and prion protein (PrPres) pattern than was observed for either classical BSE or vCJD-inoculated animals. Also, the biochemical signature of PrPres in the BASE-inoculated animal was found to have a higher proteinase K sensitivity of the octa-repeat region. We found the same biochemical signature in three of four human patients with sporadic CJD and an MM type 2 PrP genotype who lived in the same country as the infected bovine.

Conclusion/Significance Our results point to a possibly higher degree of pathogenicity of BASE than classical BSE in primates and also raise a question about a possible link to one uncommon subset of cases of apparently sporadic CJD. Thus, despite the waning epidemic of classical BSE, the occurrence of atypical strains should temper the urge to relax measures currently in place to protect public health from accidental contamination by BSE-contaminated products.

Citation: Comoy EE, Casalone C, Lescoutra-Etchegaray N, Zanusso G, Freire S, et al. (2008) Atypical BSE (BASE) Transmitted from Asymptomatic Aging Cattle to a Primate. PLoS ONE 3(8): e3017. doi:10.1371/journal.pone.0003017

Editor: Neil Mabbott, University of Edinburgh, United Kingdom

Received: April 24, 2008; Accepted: August 1, 2008; Published: August 20, 2008

Copyright: © 2008 Comoy et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Funding: This work has been supported by the Network of Excellence NeuroPrion.

Competing interests: CEA owns a patent covering the BSE diagnostic tests commercialized by the company Bio-Rad.

* E-mail: mhtml:%7B33B38F65-8D2E-434D-8F9B-8BDCD77D3066%7Dmid://00000110/!x-usc:mailto:emmanuel.comoy@cea.fr

http://www.plosone.org/article/info:doi/10.1371/journal.pone.0003017

FC5.5.1

BASE Transmitted to Primates and MV2 sCJD Subtype Share PrP27-30 and PrPSc C-terminal Truncated Fragments

Zanusso, G1; Commoy, E2; Fasoli, E3; Fiorini, M3; Lescoutra, N4; Ruchoux, MM4; Casalone, C5; Caramelli, M5; Ferrari, S3; Lasmezas, C6; Deslys, J-P4; Monaco, S3 1University of Verona, of Neurological and Visual Sciences, Italy; 2CEA, IMETI/SEPIA, France; 3University of Verona, Neurological and Visual Sciences, Italy; 4IMETI/SEPIA, France; 5IZSPLVA, Italy; 6The Scripps Research Insitute, USA

The etiology of sporadic Creutzfeldt-Jakob disease (sCJD), the most frequent human prion disease, remains still unknown. The marked disease phenotype heterogeneity observed in sCJD is thought to be influenced by the type of proteinase K-resistant prion protein, or PrPSc (type 1 or type 2 according to the electrophoretic mobility of the unglycosylated backbone), and by the host polymorphic Methionine/Valine (M/V) codon 129 of the PRNP. By using a two-dimensional gel electrophoresis (2D-PAGE) and imunoblotting we previously showed that in sCJD, in addition to the PrPSc type, distinct PrPSc C-terminal truncated fragments (CTFs) correlated with different sCJD subtypes. Based on the combination of CTFs and PrPSc type, we distinguished three PrPSc patterns: (i) the first was observed in sCJD with PrPSc type 1 of all genotypes,; (ii) the second was found in M/M-2 (cortical form); (iii) the third in amyloidogenic M/V- 2 and V/V-2 subtypes (Zanusso et al., JBC 2004) . Recently, we showed that sCJD subtype M/V-2 shared molecular and pathological features with an atypical form of BSE, named BASE, thus suggesting a potential link between the two conditions. This connection was further confirmed after 2D-PAGE analysis, which showed an identical PrPSc signature, including the biochemical pattern of CTFs. To pursue this issue, we obtained brain homogenates from Cynomolgus macaques intracerebrally inoculated with brain homogenates from BASE. Samples were separated by using a twodimensional electrophoresis (2D-PAGE) followed by immunoblotting. ***We here show that the PrPSc pattern obtained in infected primates is identical to BASE and sCJD MV-2 subtype. These data strongly support the link, or at least a common ancestry, between a sCJD subtype and BASE. This work was supported by Neuroprion (FOOD-CT-2004-506579)

FC5.5.2

Transmission of Italian BSE and BASE Isolates in Cattle Results into a Typical BSE Phenotype and a Muscle Wasting Disease

Zanusso, G1; Lombardi, G2; Casalone, C3; D'Angelo, A4; Gelmetti, D2; Torcoli, G2; Barbieri, I2; Corona, C3; Fasoli, E1; Farinazzo, A1; Fiorini, M1; Gelati, M1; Iulini, B3; Tagliavini, F5; Ferrari, S1; Monaco, S1; Caramelli, M3; Capucci, L2 1University of Verona, Neurological and Visual Sciences, Italy; 2IZSLER, Italy; 3IZSPLVA, Italy; 4University of Turin, Animal Pathology, Italy; 5Isituto Carlo Besta, Italy

The clinical phenotype of bovine spongiform encephalopathy has been extensively reported in early accounts of the disorder. Following the introduction of statutory active surveillance, almost all BSE cases have been diagnosed on a pathological/molecular basis, in a pre-symptomatic clinical stage. In recent years, the active surveillance system has uncovered atypical BSE cases, which are characterized by distinct conformers of the PrPSc, named high-type (BSE-H) and low-type (BSE-L), whose clinicopathological phenotypes remain unknown. We recently reported two Italian atypical cases with a PrPSc type similar to BSE-L, pathologically characterized by PrP amyloid plaques. Experimental transmission to TgBov mice has recently disclosed that BASE is caused by a distinct prion strain which is extremely virulent. A major limitation of transmission studies to mice is the lack of reliable information on clinical phenotype of BASE in its natural host. In the present study, we experimentally infected Fresian/Holstein and Alpine/Brown cattle with Italian BSE and BASE isolates by i.c. route. BASE infected cattle showed survival times significantly shorter than BSE, a finding more readily evident in Fresian/Holstein, and in keeping with previous observations in TgBov mice. Clinically, BSE-infected cattle developed a disease phenotype highly comparable with that described in field BSE cases and in experimentally challenged cattle. On the contrary, BASE-inoculated cattle developed an amyotrophic disorder accompanied by mental dullness. The molecular and neuropathological profiles, including PrP deposition pattern, closely matched those observed in the original cases. ***This study further confirms that BASE is caused by a distinct prion isolate and discloses a novel disease phenotype in cattle, closely resembling the phenotype previous reported in scrapie-inoculated cattle and in some subtypes of inherited and sporadic Creutzfeldt-Jakob disease.

P02.35

Molecular Features of the Protease-resistant Prion Protein (PrPres) in H-type BSE

Biacabe, A-G1; Jacobs, JG2; Gavier-Widén, D3; Vulin, J1; Langeveld, JPM2; Baron, TGM1 1AFSSA, France; 2CIDC-Lelystad, Netherlands; 3SVA, Sweden

Western blot analyses of PrPres accumulating in the brain of BSE-infected cattle have demonstrated 3 different molecular phenotypes regarding to the apparent molecular masses and glycoform ratios of PrPres bands. We initially described isolates (H-type BSE) essentially characterized by higher PrPres molecular mass and decreased levels of the diglycosylated PrPres band, in contrast to the classical type of BSE. This type is also distinct from another BSE phenotype named L-type BSE, or also BASE (for Bovine Amyloid Spongiform Encephalopathy), mainly characterized by a low representation of the diglycosylated PrPres band as well as a lower PrPres molecular mass. Retrospective molecular studies in France of all available BSE cases older than 8 years old and of part of the other cases identified since the beginning of the exhaustive surveillance of the disease in 20001 allowed to identify 7 H-type BSE cases, among 594 BSE cases that could be classified as classical, L- or H-type BSE. By Western blot analysis of H-type PrPres, we described a remarkable specific feature with antibodies raised against the C-terminal region of PrP that demonstrated the existence of a more C-terminal cleaved form of PrPres (named PrPres#2 ), in addition to the usual PrPres form (PrPres #1). In the unglycosylated form, PrPres #2 migrates at about 14 kDa, compared to 20 kDa for PrPres #1. The proportion of the PrPres#2 in cattle seems to by higher compared to the PrPres#1. Furthermore another PK-resistant fragment at about 7 kDa was detected by some more N-terminal antibodies and presumed to be the result of cleavages of both N- and C-terminal parts of PrP. These singular features were maintained after transmission of the disease to C57Bl/6 mice. ***The identification of these two additional PrPres fragments (PrPres #2 and 7kDa band) reminds features reported respectively in sporadic Creutzfeldt-Jakob disease and in Gerstmann-Sträussler-Scheinker (GSS) syndrome in humans.

http://www.neuroprion.com/pdf_docs/conferences/prion2007/abstract_book.pdf

And last but not least, similarities of PrPres between Htype BSE and human prion diseases like CJD or GSS have been put forward [10], as well as between L-type BSE and CJD [17]. These findings raise questions about the origin and inter species transmission of these prion diseases that were discovered through the BSE active surveillance.

full text 18 pages ;

http://www.vetres.org/index.php?option=article&access=standard&Itemid=129&url=/articles/vetres/pdf/2008/04/v07232.pdf

please see full text ;

http://bse-atypical.blogspot.com/2008/06/review-on-epidemiology-and-dynamics-of.html

P.4.23

Transmission of atypical BSE in humanized mouse models

Liuting Qing1, Wenquan Zou1, Cristina Casalone2, Martin Groschup3, Miroslaw Polak4, Maria Caramelli2, Pierluigi Gambetti1, Juergen Richt5, Qingzhong Kong1 1Case Western Reserve University, USA; 2Instituto Zooprofilattico Sperimentale, Italy; 3Friedrich-Loeffler-Institut, Germany; 4National Veterinary Research Institute, Poland; 5Kansas State University (Previously at USDA National Animal Disease Center), USA

Background: Classical BSE is a world-wide prion disease in cattle, and the classical BSE strain (BSE-C) has led to over 200 cases of clinical human infection (variant CJD). Atypical BSE cases have been discovered in three continents since 2004; they include the L-type (also named BASE), the H-type, and the first reported case of naturally occurring BSE with mutated bovine PRNP (termed BSE-M). The public health risks posed by atypical BSE were largely undefined.

Objectives: To investigate these atypical BSE types in terms of their transmissibility and phenotypes in humanized mice. Methods: Transgenic mice expressing human PrP were inoculated with several classical (C-type) and atypical (L-, H-, or Mtype) BSE isolates, and the transmission rate, incubation time, characteristics and distribution of PrPSc, symptoms, and histopathology were or will be examined and compared.

Results: Sixty percent of BASE-inoculated humanized mice became infected with minimal spongiosis and an average incubation time of 20-22 months, whereas only one of the C-type BSE-inoculated mice developed prion disease after more than 2 years. Protease-resistant PrPSc in BASE-infected humanized Tg mouse brains was biochemically different from bovine BASE or sCJD. PrPSc was also detected in the spleen of 22% of BASE-infected humanized mice, but not in those infected with sCJD. Secondary transmission of BASE in the humanized mice led to a small reduction in incubation time.*** The atypical BSE-H strain is also transmissible with distinct phenotypes in the humanized mice, but no BSE-M transmission has been observed so far.

Discussion: Our results demonstrate that BASE is more virulent than classical BSE, has a lymphotropic phenotype, and displays a modest transmission barrier in our humanized mice. BSE-H is also transmissible in our humanized Tg mice. The possibility of more than two atypical BSE strains will be discussed.

Supported by NINDS NS052319, NIA AG14359, and NIH AI 77774.

P02.16

Analysis of Bovine Prion Protein Gene Sequence Variation in Animals with Classical and Atypical BSE

Polak, MP; Larska, M; Rola, J; Zmudzinski, JF National Veterinary Research Institute, Department of Virology, Poland B.

Variation within prion protein gene sequence have major impact on the susceptibility to prion diseases in humans and sheep. However no major differences between healthy cattle and bovine spongiform encephalopathy (BSE) affected individuals were identified. Recent studies indicate that susceptibility to bovine spongiform encephalopathy is associated with 23-base pair (bp) and 12-bp indel sequences. Identification of atypical BSE in older cattle in several countries pointed at the possibility of spontaneous origin of this new form of prion disease due to possible mutations within prion gene (PRNP) sequence. A./O. Therefore the aim of the study was to analyze and to compare prion protein gene sequences in animals showing classical and atypical BSE for any genetic traits differentating both forms of the disease. M. Analysis included: octapeptide-repeat polymorphism; sequence analysis of exon 3 region; deletion/insertion polymorphism within the promoter sequence (23-bp), intron 1 (12-bp) and 3'untranslated region - UTR (14-bp) of PRNP gene. R. No major differences were found as for the octapeptide-repeats. Most dominant genotype in both classical and atypical BSE involved 6/6 homozygous animals. Sequence comparison within exon 3 region also showed no differences. Results from indel sequence analysis within three regions of PRNP gene were also quite uniform between both forms of BSE. D. Therefore no genetic traits explaining the appearance of atypical BSE could be found. However, it is too early to reject the hypothesis that genetic makeup is not involved in atypical BSE. Further and more detailed studies including more cases of atypical BSE would be more reliable to draw such a conclusion.

O.10.6

Biological typing of sporadic Creutzfeldt- Jakob disease isolates and comparison with animal prion isolates

Romolo Nonno1, Michele Di Bari1, Laura Pirisinu1, Stefano Marcon1, Claudia D'Agostino1, Elena Esposito1, Paola Fazzi1, Shimon Simson1, Paolo Frassanito1, Cristina Casalone3, Franco Cardone2, Maurizio Pocchiari2, Gabriele Vaccari1, Umberto Agrimi1 1Dept. SPVSA, Istituto Superiore di Sanità, Italy; 2Dept. BCN, Istituto Superiore di Sanità, Italy; 3Istituto Zooprofilattico del Piemonte, Liguria e Valle D'Aosta, Italy

Background: Our incomplete understanding of the nature of TSE agents, along with the current technical limitations in the analysis of PrPSc structure, prevent the direct typing of prion isolates. The characterization of prion strains still relies upon bioassay in rodents. Bank vole (Myodes glareolus), being susceptible to a wide range of prion sources, offers the opportunity to investigate the biological properties of prion isolates from different species in a single model.

Objectives: To study the biological properties of sCJD subtypes and compare them with animal TSEs. Methods: We analysed the phenotype of transmission of MM1, MV1, MM2, MV2, and VV2 sCJD subtypes to voles, in comparison with BSE, BASE and classical scrapie isolates from different EU countries. Molecular analysis of PrPSc from the original isolates preceded voles inoculation. Survival time and attack rate were calculated upon primary transmissions and subsequent passages. The brain of voles were analysed by WB for PrPSc type, by Gnd- HCl denaturation for PrPSc conformational stability, by immunohistochemistry and PET-blot for PrPSc deposition pattern and by E&E for lesion profile.

Results: This study demonstrated that prion diseases induce in voles a variety of molecular and pathological phenotypes. CJD isolates were grouped into 4 categories: i) MM1/MV1 (n=3), ii) MM2 (n=1), iii) MV2 (n=2) and iv) VV2 (n=1). Scrapie isolates were categorised in at least 4 groups, with no overlapping with sCJD isolates. BSE was distinct from scrapie and sCJD phenotypes. Finally, BASE gave a phenotype distinct from BSE and scrapie but indistinguishable from VV2 sCJD.

Discussion: Overall, the biological classification of sCJD subtypes concurs with their clinico-pathological classification.*** Similarities in the transmission pattern of prion isolates from different host species were very rare, with the notable exception of BASE and VV2 sCJD. Herein, the meaning of such similarities is discussed in the context of current knowledge on strains and of available tools for their typing.

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

P26 TRANSMISSION OF ATYPICAL BOVINE SPONGIFORM ENCEPHALOPATHY (BSE) IN HUMANIZED MOUSE MODELS

Liuting Qing1, Fusong Chen1, Michael Payne1, Wenquan Zou1, Cristina Casalone2, Martin Groschup3, Miroslaw Polak4, Maria Caramelli2, Pierluigi Gambetti1, Juergen Richt5*, and Qingzhong Kong1 1Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA; 2CEA, Istituto Zooprofilattico Sperimentale, Italy; 3Friedrich-Loeffler-Institut, Germany; 4National Veterinary Research Institute, Poland; 5Kansas State University, Diagnostic Medicine/Pathobiology Department, Manhattan, KS 66506, USA. *Previous address: USDA National Animal Disease Center, Ames, IA 50010, USA

Classical BSE is a world-wide prion disease in cattle, and the classical BSE strain (BSE-C) has led to over 200 cases of clinical human infection (variant CJD). Two atypical BSE strains, BSE-L (also named BASE) and BSE-H, have been discovered in three continents since 2004. The first case of naturally occurring BSE with mutated bovine PrP gene (termed BSE-M) was also found in 2006 in the USA. The transmissibility and phenotypes of these atypical BSE strains/isolates in humans were unknown. We have inoculated humanized transgenic mice with classical and atypical BSE strains (BSE-C, BSE-L, BSE-H) and the BSE-M isolate. We have found that the atypical BSE-L strain is much more virulent than the classical BSE-C.*** The atypical BSE-H strain is also transmissible in the humanized transgenic mice with distinct phenotype, but no transmission has been observed for the BSE-M isolate so far.

III International Symposium on THE NEW PRION BIOLOGY: BASIC SCIENCE, DIAGNOSIS AND THERAPY 2 - 4 APRIL 2009, VENEZIA (ITALY)

http://www.istitutoveneto.it/prion_09/Abstracts_09.pdf

I ask Professor Kong ;

Thursday, December 04, 2008 3:37 PM Subject: RE: re--Chronic Wating Disease (CWD) and Bovine Spongiform Encephalopathies (BSE): Public Health Risk Assessment

''IS the h-BSE more virulent than typical BSE as well, or the same as cBSE, or less virulent than cBSE? just curious.....''

Professor Kong reply ;

.....snip

''As to the H-BSE, we do not have sufficient data to say one way or another, but we have found that H-BSE can infect humans. I hope we could publish these data once the study is complete. Thanks for your interest.''

Best regards, Qingzhong Kong, PhD Associate Professor Department of Pathology Case Western Reserve University Cleveland, OH 44106 USA

END...TSS

Tuesday, November 02, 2010

BSE - ATYPICAL LESION DISTRIBUTION (RBSE 92-21367) statutory (obex only) diagnostic criteria CVL 1992

http://bse-atypical.blogspot.com/2010/11/bse-atypical-lesion-distribution-rbse.html

BSE prions propagate as either variant CJD-like or sporadic CJD-like prion strains in transgenic mice expressing human prion protein

Emmanuel A. Asante, Jacqueline M. Linehan, Melanie Desbruslais, Susan Joiner, Ian Gowland, Andrew L. Wood, Julie Welch, Andrew F. Hill, Sarah E. Lloyd, Jonathan D.F. Wadsworth, and John Collinge1 MRC Prion Unit and Department of Neurodegenerative Disease, Institute of Neurology, University College, Queen Square, London WC1N 3BG, UK 1Corresponding author e-mail: j.collinge@prion.ucl.ac.ukReceived August 1, 2002; Revised September 24, 2002; Accepted October 17, 2002.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC136957/?tool=pubmed

The EMBO Journal (2002) 21, 6358 - 6366 doi:10.1093/emboj/cdf653

BSE prions propagate as either variant CJD-like or sporadic CJD-like prion strains in transgenic mice expressing human prion protein

Emmanuel A. Asante1, Jacqueline M. Linehan1, Melanie Desbruslais1, Susan Joiner1, Ian Gowland1, Andrew L. Wood1, Julie Welch1, Andrew F. Hill1, Sarah E. Lloyd1, Jonathan D.F. Wadsworth1 and John Collinge1

1.MRC Prion Unit and Department of Neurodegenerative Disease, Institute of Neurology, University College, Queen Square, London WC1N 3BG, UK Correspondence to:

John Collinge, E-mail: j.collinge@prion.ucl.ac.uk

Received 1 August 2002; Accepted 17 October 2002; Revised 24 September 2002

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

Abstract

Variant Creutzfeldt-Jakob disease (vCJD) has been recognized to date only in individuals homozygous for methionine at PRNP codon 129. Here we show that transgenic mice expressing human PrP methionine 129, inoculated with either bovine spongiform encephalopathy (BSE) or variant CJD prions, may develop the neuropathological and molecular phenotype of vCJD, consistent with these diseases being caused by the same prion strain. Surprisingly, however, BSE transmission to these transgenic mice, in addition to producing a vCJD-like phenotype, can also result in a distinct molecular phenotype that is indistinguishable from that of sporadic CJD with PrPSc type 2. These data suggest that more than one BSE-derived prion strain might infect humans; it is therefore possible that some patients with a phenotype consistent with sporadic CJD may have a disease arising from BSE exposure.

Keywords:BSE, Creutzfeldt-Jakob disease, prion, transgenic

http://www.nature.com/emboj/journal/v21/n23/abs/7594869a.html

Archive Number 20101206.4364 Published Date 06-DEC-2010 Subject PRO/AH/EDR> Prion disease update 2010 (11)

PRION DISEASE UPDATE 2010 (11)

SEE;

TAFS1 Position Paper on Position Paper on Relaxation of the Feed Ban in the EU Berne, 2010 TAFS

INTERNATIONAL FORUM FOR TRANSMISSIBLE ANIMAL DISEASES AND FOOD SAFETY a non-profit Swiss Foundation

http://www.promedmail.org/pls/apex/f?p=2400:1001:5492868805159684::NO::F2400_P1001_BACK_PAGE,F2400_P1001_PUB_MAIL_ID:1000,86129

10,000,000+ LBS. of PROHIBITED BANNED MAD COW FEED I.E. BLOOD LACED MBM IN COMMERCE USA 2007

Date: March 21, 2007 at 2:27 pm PST

RECALLS AND FIELD CORRECTIONS: VETERINARY MEDICINES -- CLASS II

___________________________________

PRODUCT

Bulk cattle feed made with recalled Darling's 85% Blood Meal, Flash Dried, Recall # V-024-2007

CODE

Cattle feed delivered between 01/12/2007 and 01/26/2007

RECALLING FIRM/MANUFACTURER

Pfeiffer, Arno, Inc, Greenbush, WI. by conversation on February 5, 2007.

Firm initiated recall is ongoing.

REASON

Blood meal used to make cattle feed was recalled because it was cross- contaminated with prohibited bovine meat and bone meal that had been manufactured on common equipment and labeling did not bear cautionary BSE statement.

VOLUME OF PRODUCT IN COMMERCE

42,090 lbs.

DISTRIBUTION

WI

___________________________________

PRODUCT

Custom dairy premix products: MNM ALL PURPOSE Pellet, HILLSIDE/CDL Prot- Buffer Meal, LEE, M.-CLOSE UP PX Pellet, HIGH DESERT/ GHC LACT Meal, TATARKA, M CUST PROT Meal, SUNRIDGE/CDL PROTEIN Blend, LOURENZO, K PVM DAIRY Meal, DOUBLE B DAIRY/GHC LAC Mineral, WEST PIONT/GHC CLOSEUP Mineral, WEST POINT/GHC LACT Meal, JENKS, J/COMPASS PROTEIN Meal, COPPINI - 8# SPECIAL DAIRY Mix, GULICK, L-LACT Meal (Bulk), TRIPLE J - PROTEIN/LACTATION, ROCK CREEK/GHC MILK Mineral, BETTENCOURT/GHC S.SIDE MK-MN, BETTENCOURT #1/GHC MILK MINR, V&C DAIRY/GHC LACT Meal, VEENSTRA, F/GHC LACT Meal, SMUTNY, A- BYPASS ML W/SMARTA, Recall # V-025-2007

CODE

The firm does not utilize a code - only shipping documentation with commodity and weights identified.

RECALLING FIRM/MANUFACTURER

Rangen, Inc, Buhl, ID, by letters on February 13 and 14, 2007. Firm initiated recall is complete.

REASON

Products manufactured from bulk feed containing blood meal that was cross contaminated with prohibited meat and bone meal and the labeling did not bear cautionary BSE statement.

VOLUME OF PRODUCT IN COMMERCE

9,997,976 lbs.

DISTRIBUTION

ID and NV

END OF ENFORCEMENT REPORT FOR MARCH 21, 2007

http://www.fda.gov/Safety/Recalls/EnforcementReports/2007/ucm120446.htm

Discussion: The C, L and H type BSE cases in Canada exhibit molecular characteristics similar to those described for classical and atypical BSE cases from Europe and Japan. This supports the theory that the importation of BSE contaminated feedstuff is the source of C-type BSE in Canada. *It also suggests a similar cause or source for atypical BSE in these countries.

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

Saturday, November 6, 2010

TAFS1 Position Paper on Position Paper on Relaxation of the Feed Ban in the EU Berne, 2010 TAFS

INTERNATIONAL FORUM FOR TRANSMISSIBLE ANIMAL DISEASES AND FOOD SAFETY a non-profit Swiss Foundation

http://madcowfeed.blogspot.com/2010/11/tafs1-position-paper-on-position-paper.html

Saturday, August 14, 2010

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

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

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

Sunday, March 27, 2011

SCRAPIE USA UPDATE FEBRUARY 2011

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

and why do we not want to do TSE transmission studies on chimpanzees $

snip...

5. A positive result from a chimpanzee challenged severly would likely create alarm in some circles even if the result could not be interpreted for man. I have a view that all these agents could be transmitted provided a large enough dose by appropriate routes was given and the animals kept long enough. Until the mechanisms of the species barrier are more clearly understood it might be best to retain that hypothesis.

snip...

R. BRADLEY

http://collections.europarchive.org/tna/20080102222950/http://www.bseinquiry.gov.uk/files/yb/1990/09/23001001.pdf

Monday, April 25, 2011

Experimental Oral Transmission of Atypical Scrapie to Sheep

Volume 17, Number 5–May 2011

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

Atypical/Nor98 Scrapie Infectivity in Sheep Peripheral Tissues

Olivier Andréoletti1*, Leonor Orge2, Sylvie L. Benestad3, Vincent Beringue4, Claire Litaise1, Stéphanie Simon5, Annick Le Dur4, Hubert Laude4, Hugh Simmons6, Séverine Lugan1, Fabien Corbière1, Pierrette Costes1, Nathalie Morel5, François Schelcher1, Caroline Lacroux1

1 UMR INRA ENVT 1225, Interactions Hôtes Agents Pathogènes, Ecole Nationale Vétérinaire de Toulouse, Toulouse, France, 2 Laboratório Nacional de Investigação Veterinária, Lisboa, Portugal, 3 National Veterinary Institute, Oslo, Norway, 4 INRA UR892, Virologie et Immunologie Moléculaires, INRA, F-78350 Jouy-en-Josas, France, 5 CEA, Service de Pharmacologie et d'Immunoanalyse, IBiTec-S, DSV, CEA/Saclay, Gif sur Yvette cedex, France, 6 VLA Weybridge, ASU, Addlestone, Surrey, United Kingdom

Abstract

Atypical/Nor98 scrapie was first identified in 1998 in Norway. It is now considered as a worldwide disease of small ruminants and currently represents a significant part of the detected transmissible spongiform encephalopathies (TSE) cases in Europe. Atypical/Nor98 scrapie cases were reported in ARR/ARR sheep, which are highly resistant to BSE and other small ruminants TSE agents. The biology and pathogenesis of the Atypical/Nor98 scrapie agent in its natural host is still poorly understood. However, based on the absence of detectable abnormal PrP in peripheral tissues of affected individuals, human and animal exposure risk to this specific TSE agent has been considered low. In this study we demonstrate that infectivity can accumulate, even if no abnormal PrP is detectable, in lymphoid tissues, nerves, and muscles from natural and/or experimental Atypical/Nor98 scrapie cases. Evidence is provided that, in comparison to other TSE agents, samples containing Atypical/Nor98 scrapie infectivity could remain PrPSc negative. This feature will impact detection of Atypical/Nor98 scrapie cases in the field, and highlights the need to review current evaluations of the disease prevalence and potential transmissibility. Finally, an estimate is made of the infectivity loads accumulating in peripheral tissues in both Atypical/Nor98 and classical scrapie cases that currently enter the food chain. The results obtained indicate that dietary exposure risk to small ruminants TSE agents may be higher than commonly believed.

http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1001285

Increased Atypical Scrapie Detections

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

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

PUTTING THE CART BEFORE THE HORSE, in terms of human health risk $$$

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

Wednesday, February 16, 2011

IN CONFIDENCE

SCRAPIE TRANSMISSION TO CHIMPANZEES

IN CONFIDENCE

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

Monday, March 21, 2011

Sheep and Goat BSE Propagate More Efficiently than Cattle BSE in Human PrP Transgenic Mice

snip...

On the other hand, this component would not be distinguishable from bovine-passaged BSE prions due to the current limits of the standard biological methods and/or the molecular tools employed here to characterize prion strains. Whatever the mechanism, the notion that a passage through an intermediate species can profoundly alter prion virulence for the human species has important public-health issues, regarding emerging and/or expanding TSEs, like atypical scrapie or CWD.

snip...

Taken all together, our results suggest that the possibility of a small ruminant BSE prion as vCJD causal agent could not be ruled out, which has important implications on public and animal health policies. On one hand, although the exact magnitude and characteristic of the vCJD epidemic is still unclear, its link with cattle BSE is supported by strong epidemiological ground and several experimental data. On the other hand, the molecular typing performed in our studies, indicates that the biochemical characteristics of the PrPres detected in brains of our sheep and goat BSE-inoculated mice seem to be indistinguishable from that observed in vCJD. Considering the similarity in clinical manifestation of BSE- and scrapie-affected sheep [48], a masker effect of scrapie over BSE, as well as a potential adaptation of the BSE agent through subsequent passages, could not be ruled out. As BSE infected sheep PrPSc have been detected in many peripheral organs, small ruminant-passaged BSE prions might be a more widespread source of BSE infectivity compared to cattle [19], [49], [50]. This fact is even more worrying since our transmission studies suggest that apparently Met129 human PrP favours a BSE agent with ovine rather than a bovine sequence. Finally, it is evident that, although few natural cases have been described and so far we cannot draw any definitive conclusion about the origin of vCJD, we can not underestimate the risk of a potential goat and/or sheep BSE agent.

snip...

http://nor-98.blogspot.com/2011/03/sheep-and-goat-bse-propagate-more.html

Technical Abstract:

Prion strains may vary in their ability to transmit to humans and animals. Few experimental studies have been done to provide evidence of differences between U.S. strains of scrapie, which can be distinguished by incubation times in inbred mice, microscopic lesions, immunoreactivity to various antibodies, or molecular profile (electrophoretic mobility and glycoform ratio). Recent work on two U.S. isolates of sheep scrapie supports that at least two distinct strains exist based on differences in incubation time and genotype of sheep affected. One isolate (No. 13-7) inoculated intracerebrally caused scrapie in sheep AA at codon 136 (AA136) and QQ at codon 171 (QQ171) of the prion protein in an average of 19 months post-inoculation (PI) whereas a second isolate (No. x124) caused disease in less than 12 months after oral inoculation in AV136/QQ171 sheep. Striking differences were evident when further strain analysis was done in R111, VM, C57Bl6, and C57Bl6xVM (F1) mice. No. 13-7 did not induce disease in any mouse strain at any time post-inoculation (PI) nor were brain tissues positive by western blot (WB). Positive WB results were obtained from mice inoculated with isolate No. x124 starting at day 380 PI. Incubation times averaged 508, 559, 601, and 633 days PI for RIII, C57Bl6, VM, and F1 mice, respectively. Further passage will be required to characterize these scrapie strains in mice. This work provides evidence that multiple scrapie strains exist in U.S. sheep.

http://www.ars.usda.gov/research/publications/publications.htm?seq_no_115=227516

One of these isolates (TR316211) behaved like the CH1641 isolate, with PrPres features in mice similar to those in the sheep brain. From two other isolates (O100 and O104), two distinct PrPres phenotypes were identified in mouse brains, with either high (h-type) or low (l-type) apparent molecular masses of unglycosylated PrPres, the latter being similar to that observed with CH1641, TR316211, or BSE. Both phenotypes could be found in variable proportions in the brains of the individual mice. In contrast with BSE, l-type PrPres from "CH1641-like" isolates showed lower levels of diglycosylated PrPres. From one of these cases (O104), a second passage in mice was performed for two mice with distinct PrPres profiles. This showed a partial selection of the l-type phenotype in mice infected with a mouse brain with predominant l-type PrPres, and it was accompanied by a significant increase in the proportions of the diglycosylated band. These results are discussed in relation to the diversity of scrapie and BSE strains.

http://jvi.asm.org/cgi/content/full/81/13/7230?view=long&pmid=17442721

In the US, scrapie is reported primarily in sheep homozygous for 136A/171Q (AAQQ) and the disease phenotype is similar to that seen with experimental strain CH1641.

http://www.ars.usda.gov/research/publications/publications.htm?seq_no_115=182469

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

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

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

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

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

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

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

Scrapie

The two Commissions discussed the issue of 'atypical' scrapie in terms of notification requirements and the issue of the host genetic resistance. In response to questions of Members, the Code Commission clarified that 'classical' scrapie is reportable to the OIE but that 'atypical' scrapie is not reportable (in accordance with the recommendations made by the ad hoc Group on Atypical Scrapie and Atypical BSE, which met in November 2007). However, the sharing of scientific information on 'atypical' scrapie is encouraged. At this time, the Code Commission considered that more scientific information would be needed to fully address the issues associated with host genotype.

EU comment

4

OIE Terrestrial Animal Health Standards Commission / September 2010

The EU takes note of the fact that atypical scrapie is not an OIE listed disease. Nevertheless, it will remain notifiable in the EU. Moreover it must be stressed that any emergence of this disease should be notified to the OIE by Members and that scientific data should continue to be gathered.

snip...

Zoonotic Potential

Has transmission to humans been proven? (with the exception of artificial

circumstances) AND

Is human infection associated with severe consequences? (death or prolonged illness)

http://ec.europa.eu/food/international/organisations/docs/EU_comments_OIE_terrestrial_animal_health_code_en.pdf

snip...

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

Sunday, December 12, 2010

EFSA reviews BSE/TSE infectivity in small ruminant tissues News Story 2 December 2010

http://transmissiblespongiformencephalopathy.blogspot.com/2010/12/efsa-reviews-bsetse-infectivity-in.html

Monday, November 22, 2010

Atypical transmissible spongiform encephalopathies in ruminants: a challenge for disease surveillance and control

REVIEW ARTICLES

http://transmissiblespongiformencephalopathy.blogspot.com/2010/11/atypical-transmissible-spongiform.html

Sunday, April 18, 2010

SCRAPIE AND ATYPICAL SCRAPIE TRANSMISSION STUDIES A REVIEW 2010

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

Wednesday, January 19, 2011

EFSA and ECDC review scientific evidence on possible links between TSEs in animals and humans Webnachricht 19 Januar 2011

http://transmissiblespongiformencephalopathy.blogspot.com/2011/01/efsa-and-ecdc-review-scientific.html

Tuesday, January 18, 2011

Agent strain variation in human prion disease: insights from a molecular and pathological review of the National Institutes of Health series of experimentally transmitted disease

http://transmissiblespongiformencephalopathy.blogspot.com/2011/01/agent-strain-variation-in-human-prion.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

RISK OF BSE TO SHEEP VIA FEED

http://collections.europarchive.org/tna/20090114022605/http://www.bseinquiry.gov.uk/files/sc/seac31/tab01.pdf

Marion Simmons communicated surprising evidence for oral transmissibility of Nor98/atypical scrapie in neonatal sheep and although bioassay is ongoing, infectivity of the distal ileum of 12 and 24 month infected sheep is positive in Tg338 mice.

http://www.goatbse.eu/site/index.php?option=com_content&view=article&id=94:minutes-workshop-2010&catid=9:popular&Itemid=22

SUMMARY REPORTS OF MAFF BSE TRANSMISSION STUDIES AT THE CVL ;

http://collections.europarchive.org/tna/20090114023010/http://www.bseinquiry.gov.uk/files/sc/seac18/tab02b.pdf

THE RISK TO HUMANS FROM SHEEP;

http://collections.europarchive.org/tna/20090114022915/http://www.bseinquiry.gov.uk/files/sc/seac24/tab03.pdf

EXPERIMENTAL TRANSMISSION OF BSE TO SHEEP

http://collections.europarchive.org/tna/20090114023211/http://www.bseinquiry.gov.uk/files/sc/seac25/tab05.pdf

SHEEP AND BSE

PERSONAL AND CONFIDENTIAL

SHEEP AND BSE

A. The experimental transmission of BSE to sheep.

Studies have shown that the ''negative'' line NPU flock of Cheviots can be experimentally infected with BSE by intracerebral (ic) or oral challenge (the latter being equivalent to 0.5 gram of a pool of four cow brains from animals confirmed to have BSE).

http://collections.europarchive.org/tna/20090506010048/http://www.bseinquiry.gov.uk/files/sc/seac33/tab02.pdf

RB264

BSE - TRANSMISSION STUDIES

http://collections.europarchive.org/tna/20090113230127/http://www.bseinquiry.gov.uk/files/sc/Seac06/tab06.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://web.archive.org/web/20030513212324/http://www.bseinquiry.gov.uk/files/mb/m08b/tab64.pdf

P03.141

Aspects of the Cerebellar Neuropathology in Nor98

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

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

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

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

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

BSE: TIME TO TAKE H.B. PARRY SERIOUSLY

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://collections.europarchive.org/tna/20090505194948/http://bseinquiry.gov.uk/files/yb/1988/06/08004001.pdf

Suspect symptoms

What if you can catch old-fashioned CJD by eating meat from a sheep infected with scrapie?

28 Mar 01

Like lambs to the slaughter 31 March 2001 by Debora MacKenzie Magazine issue 2284. Subscribe and get 4 free issues. 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 mice as sCJD.

"This means we cannot rule out that at least some sCJD may be caused by some strains of scrapie," says team member Jean-Philippe Deslys of the French Atomic Energy Commission's medical research laboratory in Fontenay-aux-Roses, south-west of Paris. Hans Kretschmar of the University of Göttingen, who coordinates CJD surveillance in Germany, is so concerned by the findings that he now wants to trawl back through past sCJD cases to see if any might have been caused by eating infected mutton or lamb.

Scrapie has been around for centuries and until now there has been no evidence that it poses a risk to human health. But if the French finding means that scrapie can cause sCJD in people, countries around the world may have overlooked a CJD crisis to rival that caused by BSE.

Deslys and colleagues were originally studying vCJD, not sCJD. They injected the brains of macaque monkeys with brain from BSE cattle, and from French and British vCJD patients. The brain damage and clinical symptoms in the monkeys were the same for all three. Mice injected with the original sets of brain tissue or with infected monkey brain also developed the same symptoms.

As a control experiment, the team also injected mice with brain tissue from people and animals with other prion diseases: a French case of sCJD; a French patient who caught sCJD from human-derived growth hormone; sheep with a French strain of scrapie; and mice carrying a prion derived from an American scrapie strain. As expected, they all affected the brain in a different way from BSE and vCJD. But while the American strain of scrapie caused different damage from sCJD, the French strain produced exactly the same pathology.

"The main evidence that scrapie does not affect humans has been epidemiology," says Moira Bruce of the neuropathogenesis unit of the Institute for Animal Health in Edinburgh, who was a member of the same team as Deslys. "You see about the same incidence of the disease everywhere, whether or not there are many sheep, and in countries such as New Zealand with no scrapie." In the only previous comparisons of sCJD and scrapie in mice, Bruce found they were dissimilar.

But there are more than 20 strains of scrapie, and six of sCJD. "You would not necessarily see a relationship between the two with epidemiology if only some strains affect only some people," says Deslys. Bruce is cautious about the mouse results, but agrees they require further investigation. Other trials of scrapie and sCJD in mice, she says, are in progress.

People can have three different genetic variations of the human prion protein, and each type of protein can fold up two different ways. Kretschmar has found that these six combinations correspond to six clinical types of sCJD: each type of normal prion produces a particular pathology when it spontaneously deforms to produce sCJD.

But if these proteins deform because of infection with a disease-causing prion, the relationship between pathology and prion type should be different, as it is in vCJD. "If we look at brain samples from sporadic CJD cases and find some that do not fit the pattern," says Kretschmar, "that could mean they were caused by infection."

There are 250 deaths per year from sCJD in the US, and a similar incidence elsewhere. Singeltary and other US activists think that some of these people died after eating contaminated meat or "nutritional" pills containing dried animal brain. Governments will have a hard time facing activists like Singeltary if it turns out that some sCJD isn't as spontaneous as doctors have insisted.

Deslys's work on macaques also provides further proof that the human disease vCJD is caused by BSE. And the experiments showed that vCJD is much more virulent to primates than BSE, even when injected into the bloodstream rather than the brain. This, says Deslys, means that there is an even bigger risk than we thought that vCJD can be passed from one patient to another through contaminated blood transfusions and surgical instruments.

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

Monday, December 14, 2009

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

(hmmm, this is getting interesting now...TSS)

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

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

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

Prions in Skeletal Muscles of Deer with Chronic Wasting Disease

Rachel C. Angers1,*, Shawn R. Browning1,*?, Tanya S. Seward2, Christina J. Sigurdson4,?, Michael W. Miller5, Edward A. Hoover4 and Glenn C. Telling1,2,3,§ + Author Affiliations

Abstract

The emergence of chronic wasting disease (CWD) in deer and elk in an increasingly wide geographic area, as well as the interspecies transmission of bovine spongiform encephalopathy to humans in the form of variant Creutzfeldt Jakob disease, have raised concerns about the zoonotic potential of CWD. Because meat consumption is the most likely means of exposure, it is important to determine whether skeletal muscle of diseased cervids contains prion infectivity. Here bioassays in transgenic mice expressing cervid prion protein revealed the presence of infectious prions in skeletal muscles of CWD-infected deer, demonstrating that humans consuming or handling meat from CWD-infected deer are at risk to prion exposure.

Received for publication 21 November 2005. Accepted for publication 13 January 2006.

http://www.sciencemag.org/cgi/content/abstract/sci;311/5764/1117

Journal of Virology, September 2009, p. 9608-9610, Vol. 83, No. 18 0022-538X/09/$08.00+0 doi:10.1128/JVI.01127-09 Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Prion Infectivity in Fat of Deer with Chronic Wasting Disease

Brent Race,# Kimberly Meade-White,# Richard Race, and Bruce Chesebro* Rocky Mountain Laboratories, 903 South 4th Street, Hamilton, Montana 59840

Received 2 June 2009/ Accepted 24 June 2009

ABSTRACT Top ABSTRACT TEXT REFERENCES

Chronic wasting disease (CWD) is a neurodegenerative prion disease of cervids. Some animal prion diseases, such as bovine spongiform encephalopathy, can infect humans; however, human susceptibility to CWD is unknown. In ruminants, prion infectivity is found in central nervous system and lymphoid tissues, with smaller amounts in intestine and muscle. In mice, prion infectivity was recently detected in fat. Since ruminant fat is consumed by humans and fed to animals, we determined infectivity titers in fat from two CWD-infected deer. Deer fat devoid of muscle contained low levels of CWD infectivity and might be a risk factor for prion infection of other species.

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The highest risk of human contact with CWD might be through exposure to high-titer CNS tissue through accidental skin cuts or corneal contact at the time of harvest and butchering. However, the likelihood of a human consuming fat infected with a low titer of the CWD agent is much higher. It is impossible to remove all the fat present within muscle tissue, and fat consumption is inevitable when eating meat. Of additional concern is the fact that meat from an individual deer harvested by a hunter is typically consumed over multiple meals by the same group of people. These individuals would thus have multiple exposures to the CWD agent over time, which might increase the chance for transfer of infection.

In the Rocky Mountain region of North America, wild deer are subject to predation by wolves, coyotes, bears, and mountain lions. Although canines such as wolves and coyotes are not known to be susceptible to prion diseases, felines definitely are susceptible to BSE (9) and might also be infected by the CWD agent. Deer infected with the CWD agent are more likely to be killed by predators such as mountain lions (11). Peripheral tissues, including lymph nodes, muscle, and fat, which harbor prion infectivity are more accessible for consumption than CNS tissue, which has the highest level of infectivity late in disease. Therefore, infectivity in these peripheral tissues may be important in potential cross-species CWD transmissions in the wild.

The present finding of CWD infectivity in deer fat tissue raises the possibility that prion infectivity might also be found in fat tissue of other infected ruminants, such as sheep and cattle, whose fat and muscle tissues are more widely distributed in both the human and domestic-animal food chains. Although the infectivity in fat tissues is low compared to that in the CNS, there may be significant differences among species and between prion strains. Two fat samples from BSE agent-infected cattle were reported to be negative by bioassay in nontransgenic RIII mice (3, 6). However, RIII mice are 10,000-fold-less sensitive to BSE agent infection than transgenic mice expressing bovine PrP (4). It would be prudent to carry out additional infectivity assays on fat from BSE agent-infected cattle and scrapie agent-infected sheep using appropriate transgenic mice or homologous species to determine the risk from these sources.

http://jvi.asm.org/cgi/content/full/83/18/9608

THE LATEST DATA ON TISSUE INFECTIVITY

WHO Tables on Tissue Infectivity Distribution in Transmissible Spongiform Encephalopathies Updated 2010

MAJOR CATEGORIES OF INFECTIVITY: TABLES IA, IB, IC

The assignment of tissues to high, low, and undetected infectivity categories is based exclusively upon observations of naturally occurring disease, or primary experimental infection by the oral route (in ruminants). The Tables do not include results from disease models using strains of TSE that have been adapted to experimental animals, because passaged strain phenotypes can differ significantly and unpredictably from those of naturally occurring disease. However, for tissues and fluids of exceptional public health interest, such as muscle, intestine, skin, secretions and excretions, experimental results have been indicated in footnotes.

Because the detection of misfolded prion protein (PrPTSE) broadly parallels infectivity titers in various tissues [Beekes et al 1996; Andreoletti et al 2004], PrPTSE testing results are presented in parallel with bioassay data.

Although a given tissue may be positive or negative in different varieties of TSE, the expert group considered a tissue to be potentially infectious even if a positive result occurred in only a single disease. The categorical assignment of tissues will almost certainly undergo further revision as new data accumulate from increasingly sensitive tests.

IA: High-infectivity tissues: CNS tissues that attain a high titer of infectivity in the later stages of all TSEs, and certain tissues that are anatomically associated with the CNS.

IB: Lower-infectivity tissues: peripheral tissues that have tested positive for infectivity and/or PrPTSE in at least one form of TSE.

IC: Tissues with no detectable infectivity: tissues that have been examined for infectivity and/or PrPTSE with negative results.

Data entries are shown as follows:

+ Presence of infectivity or PrPTSE

- Absence of detectable infectivity or PrPTSE

NT Not tested

NA Not applicable ?

Uncertain interpretation

( ) Limited or preliminary data

[ ] Infectivity or PrPTSE data based exclusively on bioassays in transgenic

(Tg)mice over-expressing the PrP-encoding gene or PrPTSE amplification methods.

A word of caution is offered about tissues in Table IB for which positive results are so far limited to either detection of PrPTSE using amplification techniques (PMCA), or infectivity bioassays in Tg mice that over-express PrP. The amounts of pathological protein or infectious agent detected by these exquisitely sensitive assays may well fall below the threshold of transmissibility for normal animals and humans. WHO Tables on Tissue Infectivity Distribution in Transmissible Spongiform Encephalopathies 5

A good example is illustrated in the studies of urine and feces from deer infected with CWD: bioassays using normal deer as recipient subjects were negative; subsequent bioassays performed in Tg mice were positive. A similar discordance was observed for BSE muscle inoculated into cattle and Tgmice. Until more evidence is compiled showing that positive results in experimental PMCA and Tg mouse assays equate to a risk of transmitting disease under natural conditions, it cannot be assumed that such results imply the existence of a substantial risk to the health of animals or humans.

Considering the succession of updated Tables of the past few years, and the fact that inflammation has been shown to result in PrPTSE deposition in tissues that are not normally involved in TSE pathogenesis, it is evident that as testing continues, more tissues will find their way from Table IC into Table IB (but probably not from either Table IC or IB into Table IA). It is also evident that the data generated to date are far from complete, and that a great deal more work needs to be done if conclusions about the tissue distribution and significance of infectivity in a given TSE are to be based on direct measurements rather than by analogy to other forms of the disease.

Finally, it is critically important to understand that categories of infectivity are not the same as categories of risk, which require consideration not only of the level of infectivity in tissue, but also of the amount of tissue to which a person or animal is exposed, and the route by which infection is transmitted. For example, although the level of tissue infectivity is the most important factor in estimating the risk of transmission by instrument crosscontamination during surgical procedures (e.g., neurosurgery versus general surgery), it will be only one determinant of the risk of transmission by blood transfusions, in which a large amount of low-infectivity blood is administered intravenously, or the risk of transmission by foodstuffs that, irrespective of high or low infectivity, involve a comparatively inefficient oral route of infection.

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Table IC: Tissues with no detected infectivity or PrPTSE

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Musculo-skeletal tissues

Bone NT - NT - - NT NT NT NT NT

Tendon NT - NT - - NT NT NT NT NT

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please see full text with tables here ;

WHO Tables on Tissue Infectivity Distribution in Transmissible Spongiform Encephalopathies Updated 2010

also in the references at bottom i saw ;

12. A single positive marrow in multiple transmission attempts from cattle orally dosed with BSE-infected brain [Wells et al., 1999; Wells et al., 2005; Sohn et al., 2009].

http://www.who.int/bloodproducts/tablestissueinfectivity.pdf

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

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

Saturday, March 5, 2011

MAD COW ATYPICAL CJD PRION TSE CASES WITH CLASSIFICATIONS PENDING ON THE RISE IN NORTH AMERICA

http://transmissiblespongiformencephalopathy.blogspot.com/2011/03/mad-cow-atypical-cjd-prion-tse-cases.html

Saturday, April 30, 2011

Blood product, collected from a donor who was at risk for variant Creutzfeldt-Jakob disease (vCJD), was distributed APRIL 27, 2011

http://vcjdtransfusion.blogspot.com/2011/04/blood-product-collected-from-donor-who.html

PRION TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY PROJECTS, RESEARCH FUNDING, BSE VOLUNTARY TESTING UPDATE IN NORTH AMERICA 2011

USA PRION FUNDING 2011

"which includes the ___elimination___ of Prion activities ($5,473,000),"

All Other Emerging and Zoonotic Infectious Diseases CDC‘s FY 2012 request of $52,658,000 for all other emerging and zoonotic infectious disease activities is a decrease of $13,607,000 below the FY 2010 level, which includes the elimination of Prion activities ($5,473,000), a reduction for other cross-cutting infectious disease activities, and administrative savings. These funds support a range of critical emerging and zoonotic infectious disease programs such Lyme Disease, Chronic Fatigue Syndrome, and Special Pathogens, as well as other activities described below.

http://www.cdc.gov/fmo/topic/Budget%20Information/appropriations_budget_form_pdf/FY2012_CDC_CJ_Final.pdf

http://prionunitusaupdate2008.blogspot.com/2011/04/prion-transmissible-spongiform.html

Einstein once said, 'The definition of insanity is doing the same thing over and over again and expecting different results.'re-transmission studies on TSE's...TSS