Friday, December 17, 2010

PRION DISEASE Action Plan National Program 103 Animal Health 2012-2017

Prion Gene PRNP ARS researchers at the Midwest Area’s Virus and Prion Research Unit in Ames, IA, identified a prion gene PRNP haplotype that associates with atypical bovine spongiform encephalopathy (BSE). Atypical BSEs are rare prion diseases that have been identified in Asian, European and North American cattle. Two cases have been confirmed within the United States. In 2007, ARS established collaboration with investigators in France, Canada and fellow ARS scientists at the National Animal Disease Center to elucidate the genetics of atypical BSE susceptibility. AHRU characterized PRNP variation in atypical BSE cases from Canada, France, and the United States and identified the haplotype association with atypical BSE. The significance of this finding isn’t the haplotype itself, but evidence that a majority of atypical BSE cases are attributable to underlying

22

FY 2009 Annual Report

genetic susceptibility. This argues against a spontaneous origin for many atypical BSE cases. This research is part of Animal Health, an ARS national program (#103).

http://www.ars.usda.gov/sp2UserFiles/Place/01090000/USDAFY2009AnnualReportonTechnologyTransferreleased7July2010FinalNSSEPT.pdf


Action Plan

National Program 103

Animal Health

2012-2017

Problem Statement 2E: Genetics of Prion Disease Susceptibility

Prion diseases have stimulated intense scientific scrutiny since it was first proposed that the infectious agent was devoid of nucleic acid. Despite this finding, host genetics has played a key role in understanding the pathobiology and clinical aspects of prion diseases through the effects of a series of polymorphisms and mutations in the prion protein gene. The advent of vCJD confirmed a powerful human genetic susceptibility factor, as all patients with clinical disease have an identical genotype at the polymorphic codon 129 of the prion gene. The alternative variant at codon 129 is not protective, however, and abnormal prions have been found in lymphoid tissues of individuals of other prion genotypes after exposure to transfused blood products from patients who later succumbed to the disease. Familial forms of prion diseases are also known to be inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In most cases, an affected person inherits the altered gene from one affected parent. In some people, familial forms of prion disease are caused by a new mutation in the prion gene. Although such people most likely do not have an affected parent, they can pass the genetic change to their children. Familial Creutzfeldt-Jakob disease (fCJD), Gerstmann-Sträussler-Scheinker (GSS) syndrome, and fatal familial insomnia (FFI) represent the core phenotypes of genetic prion disease.

Genetic studies in animals have uncovered similar polymorphisms and mutations in the prion protein gene. Genetic information has led to the discovery of genotypes with relative susceptibility and resistance to Scrapie in sheep. Current Scrapie control programs in the United States and Europe are based on the elimination of susceptible genotypes from the breeding pool. The 2006 U.S. H.-type atypical BSE cow had a polymorphism at codon 211 of the bovine prion gene, resulting in a glutamic acid to lysine substitution (E211K). This substitution is analogous to a human polymorphism associated with the most prevalent form of heritable TSE in humans, and it is considered to have caused BSE in the 2006 U.S. atypical BSE animal.

Research Needs:

The functional genomics of disease resistance are not completely understood, and recent research suggests genetic variations may lead to different clinical outcomes (e.g., vCJD, atypical BSE, atypical Scrapie). This research area is aimed at utilizing powerful computational biology and bioinformatic approaches, along with traditional animal breeding experiments, to steadily improve our understanding of mechanisms of genetic disease resistance. 18

Anticipated Products:

Genetic variations associated with disease susceptibility.

Scientific information on the correlation between host genotypes and the phenotypes of prion agents.

Genetic factors controlling susceptibility of goats to sheep Scrapie.

Scientific information to evaluate the effectiveness of disease resistance breeding programs in sheep.

Scientific information to evaluate sheep ARR/ARR genotype for resistance to different TSE strains.

Scientific information on the influence of genetics on BSE incubation time and the frequency of animals carrying the E211K allele.

Potential Benefits:

These studies will yield critical genetic information that influences disease susceptibility, clinical outcomes, surveillance programs, and the discovery of diagnostic techniques as well as preventative and treatment programs.

snip...

Component 7: Transmissible Spongiform Encephalopathies (TSEs)

Transmissible spongiform encephalopathies (TSEs) include several fatal diseases of people and animals involving degeneration of the nervous system and brain function. TSEs are caused by agents known as prions, or what appear to be primarily infectious proteins that cause normal protein (cellular-prion protein PrPc) molecules to convert into an abnormally structured form (disease-prion protein PrPsc) that can include inducement of the formation of proteinaceous deposits and plaques in the brain. TSEs include Creutzfeldt-Jakob disease (CJD), the primary human prion disease; Scrapie of sheep and goats; Chronic Wasting Disease (CWD) of deer, elk, and moose; and Bovine Spongiform Encephalopathy (BSE), also called ?mad cow,? which is the cause of variant CJD (vCJD) in people and the only TSE known to have crossed the species barrier from animals to people.

Our understanding of TSEs continues to evolve with ongoing research efforts. TSEs are progressive but long developing diseases. In humans, for example, incubation periods from the time of contact with an infectious prion may be decades long. Consequently, completion of research plans in natural hosts may require several years. Improvements have been made with the development of experimental rodent models to shorten the time required to obtain experimental results, but the relevance of any findings in mouse models remains uncertain unless confirmed and validated in natural hosts. In 2004, the Institute of Medicine of the National Academies published a report entitled: Advancing Prion Science, Guidance for the National Prion Research Program. Several federal agencies have directed resources to implement recommendations in the report, including HHS-NIH-, USDA-REE-ARS, HHS-FDA, HHS-CDC, DoD, and EPA. Although significant scientific advances have been made, the research conducted to date has yet to deliver many of the concrete solutions needed to safeguard people and animals from these devastating diseases. A critical concern is the potential for environmental, genetic, or iatrogenic events to lead to new variant TSEs that are infectious and zoonotic.

The White House Office of Science and Technology Policy (OSTP) Interagency Working Group (IWG) on Prion Science identified the following research priorities to maximize the impact of the National Prion Research Program:

Identification of the nature and origin of prion agents

Studies on the pathobiology of prion strains

Research on the determinants of transmissibility and epidemiology

Development of diagnostics, detection, and surveillance

39

These interrelated priorities represent areas with critical gaps in our knowledge base. They were selected with the aim of establishing strategic collaborations that will produce benefits by aligning core competencies across Federal agencies. Especially notable are the potential benefits to be derived from collaboration between animal health and human -biomedical research.

Stakeholders representing the sheep industries at our March 2010 Animal Health Workshop ranked research to eradicate Scrapie as their 2nd priority, and the goat industry listed it as their 6th priority.

Problem Statement 7A: Nature and Origin of Prion Agents

Significant gaps remain in our understanding of the nature and origin of disease-causing prions. Proving especially problematic is that the normal prion protein is widely expressed, particularly on neurons in the brain, and is found on cell surfaces but its function is unclear. Moreover, the origin of BSE remains a mystery, although spontaneous conversion of bovine prion to the diseased form as occurs in human Creutzfeldt-Jakob disease is one researchable hypothesis. In addition, recent evidence indicates that some forms of BSE may be genetic in nature. Another enigma of TSEs in general is that different strains are found within the same animal species.

Research Needs:

The newly discovered strains of BSE and Scrapie, so-called ?typical?strains, have yet to be fully characterized. There are also fundamental differences between TSEs in different animal species. The factors responsible for host restrictions (species-barrier) are also not fully understood. An investment in this area of research is of paramount importance and will inform all other areas of prion research.

Anticipated Products:

Scientific information on:

The physiological functions of normal prion proteins.

The biophysical and biochemical properties of abnormal prion agents.

Mechanisms of prion protein misfolding.

The origin and prevalence of scrapie in goats.

The origin and prevalence of atypical scrapie in sheep.

The origin of atypical BSE and relationship to classical disease form.

The basis for multiple TSE strains within a host species.

Potential Benefits:

This research will inform the field of prion science and is critical for advancing research programs in countermeasure discovery (see Problem Statement 7D below). Additional benefits will be derived from collaborations between animal health and biomedical research scientists resulting in animal disease models that will enhance our understanding of protein misfolding diseases, molecular neurology and genetics. 40

Problem Statement 7B: Pathobiology of Prion Strains

Important gaps remain in our basic understanding of the pathobiology of animal prion diseases. One critical need is that of understanding the invasion routes of prions and resolving the variations seen in different animal species.

Research Needs:

It is widely assumed that the oral route of infection is important in the pathogenesis of naturally occurring TSEs of livestock and cervids; however, the mechanism of transmission of TSE agents from the initial site of entry to the central nervous system is not known. A notable feature of prion diseases is a lack of detectable immune responses and inflammation during the course of a prion infection, even though immune system cells may carry prions to target tissues. To date, research in animals suggests that prion accumulation may be largely influenced by the host species affected rather than the TSE involved. An investment in comparative pathology, which has not received much experimental attention, is needed to advance research programs in epidemiology and diagnostic discovery.

Anticipated Products:

Scientific information on:

The manner in which prions enter the nervous system from peripheral sites of exposure such as a host’s gastrointestinal tract, nasal mucosa, skin, and eyes.

Mechanisms of prion spread within the nervous system.

Mechanisms controlling disease incubation time.

Mechanisms of neuropathogenesis.

The molecular underpinnings of prion strains and species barriers.

Prion distribution in goats with scrapie.

Prion distribution in cattle with atypical BSE.

Prion distribution in sheep with atypical scrapie and BSE.

Potential Benefits:

This research will inform the field of prion science of potential risks to human health associated with the newly emerging strains of TSE in various animal hosts and is critical for advancing research programs in epidemiology and diagnostic discovery (see Problem Statements 7C and 7D below).

Problem Statement 7C: Determinants of Transmissibility and Epidemiology

In interspecies transmission studies of TSEs (e.g., Scrapie, CWD) into new hosts (e.g., cattle and rodent models that have proved useful in experimental protocols), scientists have demonstrated the extent of prion accumulation in tissues. There appears to be fundamental differences between hosts but also similarities within animal species, regardless of which TSE is affecting them.

Research Needs: 41

An essential research need is the development of infection models that represent real TSEs in real target hosts. The results of this research would add insight into human transmissibility and epidemiology.

Anticipated Products:

Scientific information on:

Mechanisms by which abnormal prions are present in biological fluids.

The infectious potential of prions from biological fluids.

Infectivity time course and transmission.

The potential for transmitting scrapie prions to cervids naturally (orally).

The transmission routes of goat scrapie.

The transmission routes of CWD.

The transmission route of atypical scrapie and atypical BSE.

The transmissibility of sheep scrapie to goats and vice versa, including the effects of age and genetic factors on transmissibility.

The transmissibility of atypical BSE isolates to cattle.

Potential Benefits:

This research will directly impact the development of improved diagnostic tests (see Problem Statement 7D below), as well as surveillance programs and future measures to prevent the dissemination of TSEs in animal and human populations. The development of infection models in natural hosts will also build national capacity to implement research programs that target host-pathogen interactions and the discovery of countermeasures. Results from such studies could directly translate into a better understanding of the potential for the transmissibility of animal TSEs to humans.

Problem Statement 7D: Diagnostics, Detection, and Surveillance

Important gaps remain in our arsenal of diagnostic tools to detect TSEs. Current diagnostic tests were validated for use only on post-mortem samples; sensitive ante mortem tests have yet to be developed. Because there is no detectable immune response or inflammation during the course of TSE infection, direct tests are needed to confirm a diagnosis. At present, only highly-infected tissues, such as brain material or lymph tissue, are suitable for providing accurate diagnoses.

Research Needs:

Diagnostic approaches currently in use include techniques such as immunohistochemistry (IHC), Western blot, and enzyme-linked immunosorbent assays (ELISA). IHC is one of the original tests developed and is considered the gold standard, but it is more labor intensive and time consuming than the other two, whereas the Western blot and particularly ELISA tests are more efficient for the initial screening of large numbers of samples. Another method is the Conformation-Dependent Immunoassay (CDI), currently a research technique that claims to discriminate between normal prion and the abnormal prion on the basis of its shape, but this has yet to be validated as a diagnostic test in animals. New 42

technologies and methods have been described using protein misfolding cyclic amplification techniques (PMCA), similar in concept to gene/DNA amplification, which effectively increases the concentration of prions in normal or pathological conformations. There is a critical need to improve diagnostics methods for surveillance, including the discovery of an ante mortem test for early detection and implementation of intervention strategies.

Anticipated Products:

TSE diagnostic test capable of detecting low levels of abnormal prions (i.e., key step to enable the development of an ante mortem test that can identify disease during the early stages of incubation).

Validation of existing biopsy-based TSE tests in goats, deer, and elk.

Rapid biochemical methods for strain typing.

Validated murine models for strain typing.

Improved diagnostics for TSEs in bodily fluids, including blood in host species where this might be possible.

Technologies to distinguish infectious prions from normal cellular prion proteins.

Determination of the prevalence of proteinase K sensitive prion in the various TSEs and potential of this form to cause disparate results between IHC, WB, and ELISA tests.

Potential Benefits:

The discovery of an ante mortem diagnostic test would enable the medical community to test and discover effective treatments in people. Importantly, new and improved diagnostic platforms and an ante mortem diagnostic test for susceptible livestock will enable early detection and the implementation of effective surveillance programs, a critical step that will allow the deployment of disease prevention measures.

Component 7 Resources:

The following ARS locations have research projects addressing the problem statements identified under Component 7:

Ames, IA

Albany, CA

Ames, IA

Pullman, WA

http://www.ars.usda.gov/SP2UserFiles/Program/103/NP103ActionPlanFY12-FY17.pdf



Atypical BSEs have recently been identified in Asian, North American, and European cattle [11]. Two PRNP alleles are implicated with atypical BSE susceptibility. A non-synonymous polymorphism (E211K) was found by one of us (J.A.R.) within the prion coding region of an Htype atypical BSE case identified in the U.S. (2006). The E211K polymorphism is homologous to the human E200K polymorphism, a risk factor for genetic Creutzfeldt- Jakob disease [12], and is the suspected cause of the atypical BSE case. The 211 K allele is exceedingly rare and has not been found in other atypical BSE cases or healthy cattle [10,13,14]. However, a PRNP haplotype that is associated with atypical BSE susceptibility was found in Hand L-type atypical cases from Canada, France, and the U.S., and may have widespread involvement with atypical BSE [8]. The haplotype spans part of PRNP intron 2, the entire coding region of exon 3, and part of the three prime untranslated region of exon 3 (13 kb) [8,10]. Alleles that may be causative for atypical BSE susceptibility, including those that may be within PRNP, are thought to be linked with the implicated haplotype in atypical BSE cases [8].


http://www.ars.usda.gov/SP2UserFiles/Place/54380510/Publications/2008Reprints/BMC_Res_Notes_2008_1-32.pdf




"The significance of this finding isn’t the haplotype itself, but evidence that a majority of atypical BSE cases are attributable to underlying genetic susceptibility. This argues against a spontaneous origin for many atypical BSE cases. This research is part of Animal Health, an ARS national program (#103). FY 2009 Annual Report"


SO, what does that tell us ? tainted TSE ruminant feed maybe ?


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


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


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, March 2, 2010

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

http://madcowfeed.blogspot.com/2010/03/animal-proteins-prohibited-in-ruminant.html


Monday, March 1, 2010

ANIMAL PROTEIN I.E. MAD COW FEED IN COMMERCE A REVIEW 2010

http://madcowfeed.blogspot.com/2010/03/animal-protien-ie-mad-cow-feed-in.html


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


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


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


Sent: Saturday, December 11, 2010 3:17 PM

Subject: Species-barrier-independent prion replication in apparently resistant species

Species-barrier-independent prion replication in apparently resistant species

Pertenece a: UCL University College London Eprints

Descripción: Transmission of prions between mammalian species is thought to be limited by a "species barrier," which depends on differences in the primary structure of prion proteins in the infecting inoculum and the host, Here we demonstrate that a strain of hamster prions thought to be nonpathogenic for conventional mice leads to prion replication to high levels in such mice but without causing clinical disease. Prions pathogenic in both mice and hamsters are produced. These results demonstrate the existence of subclinical forms of prion infection with important public health implications, both with respect to iatrogenic transmission from apparently healthy humans and dietary exposure to cattle and other species exposed to bovine spongiform encephalopathy prions, Current definitions of the species barrier, which have been based on clinical endpoints, need to be fundamentally reassessed.

Autor(es): Hill, AF - Joiner, S - Linehan, J - Desbruslais, M - Lantos, PL - Collinge, J -

Fecha de contribución: 10-dic-2010

Contacto:

http://biblioteca.universia.net/html_bura/ficha/params/id/52395313.html


for those interested, see more here with comments........

Saturday, December 11, 2010

Species-barrier-independent prion replication in apparently resistant species


http://transmissiblespongiformencephalopathy.blogspot.com/2010/12/species-barrier-independent-prion.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


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


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


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


Seven main threats for the future linked to prions

The NeuroPrion network has identified 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.

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


Thursday, August 12, 2010

Seven main threats for the future linked to prions

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


http://prionpathy.blogspot.com/


AS implied in the Inset 25 we must not _ASSUME_ that transmission of BSE to other species will invariably present pathology typical of a scrapie-like disease.

snip...

http://collections.europarchive.org/tna/20080102185948/http://www.bseinquiry.gov.uk/files/yb/1991/01/04004001.pdf


Sunday, November 28, 2010

Variably protease-sensitive prionopathy in a PRNP codon 129 heterozygous UK patient with co-existing tau, a synuclein and AB pathology

http://prionopathy.blogspot.com/2010/11/variably-protease-sensitive-prionopathy.html


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


PRION 2010 Meeting Report International Prion Congress: From agent to disease; September 8–11, 2010; Salzburg, Austria Volume 4, Issue 3 July/August/September 2010

http://www.landesbioscience.com/journals/prion/article/12764/


THIS FDA recall for CWD positive product in commerce, was NOT done for the welfare of the dead CWD postive elk. ...TSS


Wednesday, March 18, 2009

Noah's Ark Holding, LLC, Dawson, MN RECALL Elk products contain meat derived from an elk confirmed to have CWD NV, CA, TX, CO, NY, UT, FL, OK RECALLS AND FIELD CORRECTIONS: FOODS CLASS II

RECALLS AND FIELD CORRECTIONS: FOODS CLASS II

___________________________________

PRODUCT a) Elk Meat, Elk Tenderloin, Frozen in plastic vacuum packaging. Each package is approximately 2 lbs., and each case is approximately 16 lbs.; Item number 755125, Recall # F-129-9;

b) Elk Meat, Elk Trim, Frozen; Item number 755155, Recall # F-130-9;

c) Elk Meat, French Rack, Chilled. Item number 755132, Recall # F-131-9;

d) Elk Meat, Nude Denver Leg. Item number 755122, Recall # F-132-9;

e) Elk Meat, New York Strip Steak, Chilled. Item number 755128, Recall # F-133-9;

f) Elk Meat, Flank Steak Frozen. Item number 755131, Recall # F-134-9; CODE Elk Meats with production dates of December 29, 30, and 31

RECALLING FIRM/MANUFACTURER

Recalling Firm: Sierra Meats, Reno, NV, by telephone on January 29, 2009 and press release on February 9, 2009. Manufacturer: Noah’s Ark Holding, LLC, Dawson, MN. Firm initiated recall is ongoing.

REASON

Elk products contain meat derived from an elk confirmed to have Chronic Wasting Disease (CWD).

VOLUME OF PRODUCT IN COMMERCE Unknown

DISTRIBUTION NV, CA, TX, CO, NY, UT, FL, OK

http://www.fda.gov/Safety/Recalls/EnforcementReports/ucm154840.htm


Sunday, April 12, 2009

CWD UPDATE Infection Studies in Two Species of Non-Human Primates and one Environmental reservoir infectivity study and evidence of two strains

snip...

From: TSS (216-119-163-189.ipset45.wt.net)

Subject: CWD aka MAD DEER/ELK TO HUMANS ???

Date: September 30, 2002 at 7:06 am PST

From: "Belay, Ermias"

To:

Cc: "Race, Richard (NIH)" ; ; "Belay, Ermias"

Sent: Monday, September 30, 2002 9:22 AM

Subject: RE: TO CDC AND NIH - PUB MED- 3 MORE DEATHS - CWD - YOUNG HUNTERS

Dear Sir/Madam, In the Archives of Neurology you quoted (the abstract of which was attached to your email), we did not say CWD in humans will present like variant CJD.

That assumption would be wrong. I encourage you to read the whole article and call me if you have questions or need more clarification (phone: 404-639-3091). Also, we do not claim that "no-one has ever been infected with prion disease from eating venison." Our conclusion stating that we found no strong evidence of CWD transmission to humans in the article you quoted or in any other forum is limited to the patients we investigated.

Ermias Belay, M.D. Centers for Disease Control and Prevention

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

From:

Sent: Sunday, September 29, 2002 10:15 AM

To: [log in to unmask]">[log in to unmask]; [log in to unmask]">[log in to unmask]; [log in to unmask]">[log in to unmask]

Subject: TO CDC AND NIH - PUB MED- 3 MORE DEATHS - CWD - YOUNG HUNTERS

Sunday, November 10, 2002 6:26 PM ......snip........end..............TSS

snip...

full text ;

http://chronic-wasting-disease.blogspot.com/2009/02/exotic-meats-usa-announces-urgent.html


http://chronic-wasting-disease.blogspot.com/2009/03/noahs-ark-holding-llc-dawson-mn-recall.html


see full text ;

http://chronic-wasting-disease.blogspot.com/2009/04/cwd-update-infection-studies-in-two.html


Tuesday, February 09, 2010

Chronic Wasting Disease: Surveillance Update North America: February 2010

"In addition, we documented horizontal transmission of CWD from inoculated mice and to un-inoculated cohabitant cage-mates."

http://ajp.amjpathol.org/cgi/content/abstract/ajpath.2010.090710v1


http://chronic-wasting-disease.blogspot.com/2010/02/chronic-wasting-disease-surveillance.html


There are now two documented strains of CWD, and science is showing that indeed CWD could transmit to humans via transmission studies ;

PPo3-7:

Prion Transmission from Cervids to Humans is Strain-dependent

Qingzhong Kong, Shenghai Huang,*Fusong Chen, Michael Payne, Pierluigi Gambetti and Liuting Qing Department of Pathology; Case western Reserve University; Cleveland, OH USA *Current address: Nursing Informatics; Memorial Sloan-Kettering Cancer Center; New York, NY USA

Key words: CWD, strain, human transmission

Chronic wasting disease (CWD) is a widespread prion disease in cervids (deer and elk) in North America where significant human exposure to CWD is likely and zoonotic transmission of CWD is a concern. Current evidence indicates a strong barrier for transmission of the classical CWD strain to humans with the PrP-129MM genotype. A few recent reports suggest the presence of two or more CWD strains. What remain unknown is whether individuals with the PrP-129VV/MV genotypes are also resistant to the classical CWD strain and whether humans are resistant to all natural or adapted cervid prion strains. Here we report that a human prion strain that had adopted the cervid prion protein (PrP) sequence through passage in cervidized transgenic mice efficiently infected transgenic mice expressing human PrP, indicating that the species barrier from cervid to humans is prion strain-dependent and humans can be vulnerable to novel cervid prion strains. Preliminary results on CWD transmission in transgenic mice expressing human PrP-129V will also be discussed.

Acknowledgement Supported by NINDS NS052319 and NIA AG14359.

PPo2-27:

Generation of a Novel form of Human PrPSc by Inter-species Transmission of Cervid Prions

Marcelo A. Barria,1 Glenn C. Telling,2 Pierluigi Gambetti,3 James A. Mastrianni4 and Claudio Soto1 1Mitchell Center for Alzheimer's disease and related Brain disorders; Dept of Neurology; University of Texas Houston Medical School; Houston, TX USA; 2Dept of Microbiology, Immunology & Molecular Genetics and Neurology; Sanders Brown Center on Aging; University of Kentucky Medical Center; Lexington, KY USA; 3Institute of Pathology; Case western Reserve University; Cleveland, OH USA; 4Dept of Neurology; University of Chicago; Chicago, IL USA

Prion diseases are infectious neurodegenerative disorders affecting humans and animals that result from the conversion of normal prion protein (PrPC) into the misfolded and infectious prion (PrPSc). Chronic wasting disease (CWD) of cervids is a prion disorder of increasing prevalence within the United States that affects a large population of wild and captive deer and elk. CWD is highly contagious and its origin, mechanism of transmission and exact prevalence are currently unclear. The risk of transmission of CWD to humans is unknown. Defining that risk is of utmost importance, considering that people have been infected by animal prions, resulting in new fatal diseases. To study the possibility that human PrPC can be converted into the infectious form by CWD PrPSc we performed experiments using the Protein Misfolding Cyclic Amplification (PMCA) technique, which mimic in vitro the process of prion replication. Our results show that cervid PrPSc can induce the pathological conversion of human PrPC, but only after the CWD prion strain has been stabilized by successive passages in vitro or in vivo. Interestingly, this newly generated human PrPSc exhibits a distinct biochemical pattern that differs from any of the currently known forms of human PrPSc, indicating that it corresponds to a novel human prion strain. Our findings suggest that CWD prions have the capability to infect humans, and that this ability depends on CWD strain adaptation, implying that the risk for human health progressively increases with the spread of CWD among cervids.

PPo2-7:

Biochemical and Biophysical Characterization of Different CWD Isolates

Martin L. Daus and Michael Beekes Robert Koch Institute; Berlin, Germany

Key words: CWD, strains, FT-IR, AFM

Chronic wasting disease (CWD) is one of three naturally occurring forms of prion disease. The other two are Creutzfeldt-Jakob disease in humans and scrapie in sheep. CWD is contagious and affects captive as well as free ranging cervids. As long as there is no definite answer of whether CWD can breach the species barrier to humans precautionary measures especially for the protection of consumers need to be considered. In principle, different strains of CWD may be associated with different risks of transmission to humans. Sophisticated strain differentiation as accomplished for other prion diseases has not yet been established for CWD. However, several different findings indicate that there exists more than one strain of CWD agent in cervids. We have analysed a set of CWD isolates from white-tailed deer and could detect at least two biochemically different forms of disease-associated prion protein PrPTSE. Limited proteolysis with different concentrations of proteinase K and/or after exposure of PrPTSE to different pH-values or concentrations of Guanidinium hydrochloride resulted in distinct isolate-specific digestion patterns. Our CWD isolates were also examined in protein misfolding cyclic amplification studies. This showed different conversion activities for those isolates that had displayed significantly different sensitivities to limited proteolysis by PK in the biochemical experiments described above. We further applied Fourier transform infrared spectroscopy in combination with atomic force microscopy. This confirmed structural differences in the PrPTSE of at least two disinct CWD isolates. The data presented here substantiate and expand previous reports on the existence of different CWD strains.

http://www.prion2010.org/bilder/prion_2010_program_latest_w_posters_4_.pdf?139&PHPSESSID=a30a38202cfec579000b77af81be3099


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


http://chronic-wasting-disease.blogspot.com/


P35

ADAPTATION OF CHRONIC WASTING DISEASE (CWD) INTO HAMSTERS, EVIDENCE OF A WISCONSIN STRAIN OF CWD

Chad Johnson1, Judd Aiken2,3,4 and Debbie McKenzie4,5 1 Department of Comparative Biosciences, University of Wisconsin, Madison WI, USA 53706 2 Department of Agriculture, Food and Nutritional Sciences, 3 Alberta Veterinary Research Institute, 4.Center for Prions and Protein Folding Diseases, 5 Department of Biological Sciences, University of Alberta, Edmonton AB, Canada T6G 2P5

The identification and characterization of prion strains is increasingly important for the diagnosis and biological definition of these infectious pathogens. Although well-established in scrapie and, more recently, in BSE, comparatively little is known about the possibility of prion strains in chronic wasting disease (CWD), a disease affecting free ranging and captive cervids, primarily in North America. We have identified prion protein variants in the white-tailed deer population and demonstrated that Prnp genotype affects the susceptibility/disease progression of white-tailed deer to CWD agent. The existence of cervid prion protein variants raises the likelihood of distinct CWD strains. Small rodent models are a useful means of identifying prion strains. We intracerebrally inoculated hamsters with brain homogenates and phosphotungstate concentrated preparations from CWD positive hunter-harvested (Wisconsin CWD endemic area) and experimentally infected deer of known Prnp genotypes. These transmission studies resulted in clinical presentation in primary passage of concentrated CWD prions. Subclinical infection was established with the other primary passages based on the detection of PrPCWD in the brains of hamsters and the successful disease transmission upon second passage. Second and third passage data, when compared to transmission studies using different CWD inocula (Raymond et al., 2007) indicate that the CWD agent present in the Wisconsin white-tailed deer population is different than the strain(s) present in elk, mule-deer and white-tailed deer from the western United States endemic region.

http://www.istitutoveneto.it/prion_09/Abstracts_09.pdf


Wednesday, November 17, 2010

CWD Update 98 November 10, 2010

http://chronic-wasting-disease.blogspot.com/2010/11/cwd-update-98-november-10-2010.html


http://chronic-wasting-disease.blogspot.com/


what about that sheep scrapie, and how the feds so freely said that sheep scrapie has and would never transmit to humans......well, think again. ...terry


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, 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


IN CONFIDENCE

IS THERE A SCRAPIE-LIKE DISEASE IN CATTLE ?

http://collections.europarchive.org/tna/20080102233201/http://www.bseinquiry.gov.uk/files/yb/1987/06/10004001.pdf


http://web.archive.org/web/20030516051623/http://www.bseinquiry.gov.uk/files/mb/m09/tab05.pdf


IN CONFIDENCE

PERCEPTIONS OF A SLOW VIRUS DISEASE IN ANIMALS IN THE USA

http://collections.europarchive.org/tna/20081106012811/http://www.bseinquiry.gov.uk/files/mb/m11b/tab01.pdf


2010

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


Sunday, September 6, 2009

MAD COW USA 1997 SECRET VIDEO

http://madcowusda.blogspot.com/2009/09/mad-cow-usa-1997-video.html


U.S.A. HIDING MAD COW DISEASE VICTIMS AS SPORADIC CJD ? see video at bottom

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


2010 PRION UPDATE

Thursday, August 12, 2010

Seven main threats for the future linked to prions

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


http://prionpathy.blogspot.com/


Tuesday, March 16, 2010

COMMONWEALTH OF AUSTRALIA Hansard Import restrictions on beef FRIDAY, 5 FEBRUARY 2010 AUSTRALIA

COMMONWEALTH OF AUSTRALIA

Proof Committee Hansard

RRA&T 2 Senate Friday, 5 February 2010

RURAL AND REGIONAL AFFAIRS AND TRANSPORT

[9.03 am]

BELLINGER, Mr Brad, Chairman, Australian Beef Association

CARTER, Mr John Edward, Director, Australian Beef Association

CHAIR—Welcome. Would you like to make an opening statement?

Mr Bellinger—Thank you. The ABA stands by its submission, which we made on 14 December last year, that the decision made by the government to allow the importation of beef from BSE affected countries is politically based, not science based. During this hearing we will bring forward compelling new evidence to back up this statement. When I returned to my property after the December hearing I received a note from an American citizen. I will read a small excerpt from the mail he sent me in order to reinforce the dangers of allowing the importation of beef from BSE affected countries. I have done a number of press releases on this topic, and this fellow has obviously picked my details up from the internet. His name is Terry Singeltary and he is from Bacliff, Texas. He states, and rightfully so:

You should be worried. Please let me explain. I’ve kept up with the mad cow saga for 12 years today, on December 14th 1997, some four months post voluntary and partial mad cow feed ban in the USA, I lost my mother to the Heidenhain variant Creutzfeldt-Jakob disease (CJD). I know this is just another phenotype of the infamous sporadic CJDs. Here in the USA, when USA sheep scrapie was transmitted to USA bovine, the agent was not UK BSE—it was a different strain. So why then would human TSE from USA cattle look like UK CJD from UK BSE? It would not. So this accentuates that the science is inconclusive still on this devastating disease. He goes on to state:

The OIE— the International Organisation of Epizootics, the arm of the WTO— is a failed global agent that in my opinion is bought off via bogus regulations for global trade and industry reps. I have done this all these years for nothing but the truth. I am a consumer, I eat meat, but I do not have to sit idly by and see the ignorance and greed of it all while countless numbers of humans and animals are being exposed to the TSE agents. All the USA is interested in is trade, nothing else matters.

Even Dr Stanley Prusiner, who incidentally won the Nobel Health Prize in 1997 for his work on the prion—he invented the word ‘prion’, or it came from him—states:

snip...see full text 110 pages ;

http://www.aph.gov.au/hansard/senate/commttee/S12742.pdf


*** 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.

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


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


for those interested, please see much more here ;


http://docket-aphis-2006-0041.blogspot.com/2010/03/commonwealth-of-australia-hansard.html


http://transmissiblespongiformencephalopathy.blogspot.com/2010/02/transmissible-spongiform-encephalopathy.html


Tuesday, December 14, 2010 TAFS1

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

http://transmissiblespongiformencephalopathy.blogspot.com/2010/12/tafs1-position-paper-on-relaxation-of.html


Tuesday, June 1, 2010

USA cases of dpCJD rising with 24 cases so far in 2010

http://cjdtexas.blogspot.com/2010/06/usa-cases-of-dpcjd-rising-with-24-cases.html


Wednesday, June 16, 2010

Defining sporadic Creutzfeldt-Jakob disease strains and their transmission properties

http://creutzfeldt-jakob-disease.blogspot.com/2010/06/defining-sporadic-creutzfeldt-jakob.html


Tuesday, December 14, 2010

Infection control of CJD, vCJD and other human prion diseases in healthcare and community settings part 4, Annex A1, Annex J, UPDATE DECEMBER 2010

http://creutzfeldt-jakob-disease.blogspot.com/2010/12/infection-control-of-cjd-vcjd-and-other.html



DID EVERYONE FILL OUT THEIR CJD QUESIONNAIRE FROM THE CDC AND OR THE CJD FOUNDATION ???


Friday, November 30, 2007

CJD QUESTIONNAIRE USA CWRU AND CJD FOUNDATION

http://cjdquestionnaire.blogspot.com/


USA

5 Includes 16 cases in which the diagnosis is pending, and 18 inconclusive cases;

6 Includes 21 (19 from 2010) cases with type determination pending in which the diagnosis of vCJD has been excluded.

2010

PLEASE NOTE REFERENCE LINES 5. AND 6.

Monday, August 9, 2010

National Prion Disease Pathology Surveillance Center Cases Examined (July 31, 2010) Year Total Referrals2 Prion Disease Sporadic Familial Iatrogenic vCJD

1996 & earlier 51 33 28 5 0 0

1997 114 68 59 9 0 0

1998 88 52 44 7 1 0

1999 120 72 64 8 0 0

2000 146 103 89 14 0 0

2001 209 119 109 10 0 0

2002 248 149 125 22 2 0

2003 274 176 137 39 0 0

2004 325 186 164 21 0 1(3)

2005 344 194 157 36 1 0

2006 383 197 166 29 0 2(4)

2007 377 214 187 27 0 0

2008 394 231 204 25 0 0

2009 425 259 216 43 0 0

2010 204 124 85 20 0 0

TOTAL 3702(5) 2177(6) 1834 315 4 3

1 Listed based on the year of death or, if not available, on year of referral;

2 Cases with suspected prion disease for which brain tissue and/or blood (in familial cases) were submitted;

3 Disease acquired in the United Kingdom;

4 Disease was acquired in the United Kingdom in one case and in Saudi Arabia in the other case;

5 Includes 16 cases in which the diagnosis is pending, and 18 inconclusive cases;

6 Includes 21 (19 from 2010) cases with type determination pending in which the diagnosis of vCJD has been excluded.

http://www.cjdsurveillance.com/pdf/case-table.pdf


Monday, August 9, 2010

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

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

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



Atypical BSE in Cattle

BSE has been linked to the human disease variant Creutzfeldt Jakob Disease (vCJD). The known exposure pathways for humans contracting vCJD are through the consumption of beef and beef products contaminated by the BSE agent and through blood transfusions. However, recent scientific evidence suggests that the BSE agent may play a role in the development of other forms of human prion diseases as well. These studies suggest that classical type of BSE may cause type 2 sporadic CJD and that H-type atypical BSE is connected with a familial form of CJD.

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.

snip...see full text ;



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



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.

page 114 ;

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



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


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


BSE101/1 0136

IN CONFIDENCE

CMO

From: Dr J S Metters DCMO

4 November 1992

TRANSMISSION OF ALZHEIMER TYPE PLAQUES TO PRIMATES


http://collections.europarchive.org/tna/20081106170650/http://www.bseinquiry.gov.uk/files/yb/1992/11/04001001.pdf


CJD1/9 0185

Ref: 1M51A

IN STRICT CONFIDENCE

From: Dr. A Wight

Date: 5 January 1993

Copies:

Dr Metters

Dr Skinner

Dr Pickles

Dr Morris

Mr Murray

TRANSMISSION OF ALZHEIMER-TYPE PLAQUES TO PRIMATES


http://collections.europarchive.org/tna/20080102191246/http://www.bseinquiry.gov.uk/files/yb/1993/01/05004001.pdf


Friday, September 3, 2010

Alzheimer's, Autism, Amyotrophic Lateral Sclerosis, Parkinson's, Prionoids, Prionpathy, Prionopathy, TSE


http://betaamyloidcjd.blogspot.com/2010/09/alzheimers-autism-amyotrophic-lateral.html


http://betaamyloidcjd.blogspot.com/


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

Tuesday, December 14, 2010

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

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

Epidemiological evidence implicated contaminated rendered meat and bone meal as the source of the BSE epidemic in the United Kingdom, continental Europe as well as a few other countries around the world. With the overall global decline of BSE cases, national governments are beginning to explore the possibility of relaxing some of the measures taken to bring the disease under control. This paper will examine the current scientific knowledge and other facets that may impact decisions regarding the feed bans.

snip...

In the view of TAFS, taking into consideration all of the scientific and epidemiological knowns and unknowns, the fact that the requirements as listed above are currently not met and acknowledging the potential for fraudulent behavior, a relaxation of the feed ban at the present time would not eliminate all risks. We feel strongly that maintenance of the ban is the only means to drive the level of risk toward zero.

http://www.tafsforum.org/position_papers/TAFS_POSITION_PAPER_ON_RELAXATION_OF_FEED_BAN_2010_v2.pdf


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

This document is a simplified and shortened version of the corresponding full position paper which should be consulted for additional details, arguments and all references.

The full position paper is available at:

http://www.tafsforum.org/position_papers/TAFS_POSITION_PAPER_ON_RELAXATION_OF_FEED_BAN_2010.pdf


http://www.tafsforum.org/position_papers/TAFS_POSITION_PAPER_ON_RELAXATION_OF_FEED_BAN_2010_SUMMARY.pdf


Atypical BSE October 27, 2006


Detwiler, a former official with USDA’s Animal and Plant Health Inspection Service, said the origin of "atypical" BSE is unknown at this stage. Speculation has focused on whether it is a variation or mutation of classical BSE, or whether it is caused by a different route of exposure, or exposure of the animal at an older age. There is no definitive evidence that "atypical" BSE occurs sporadically, she said. But scientists have shown that tissues – such as brain and spinal cord – infected with "atypical" BSE are infectious. Based upon what currently is known, she advised that cattle surveillance be maintained, and said it may be necessary to "rethink" the target population of animals tested for BSE to include more apparently healthy older cattle. She also said additional research is needed on the pathogenesis of "atypical" BSE and how it may be transmitted to cattle or other species; and she encouraged countries not to relax BSE-prevention feed restrictions.

end...tss


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


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


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


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


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


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


Saturday, December 11, 2010

Species-barrier-independent prion replication in apparently resistant species

http://transmissiblespongiformencephalopathy.blogspot.com/2010/12/species-barrier-independent-prion.html


Sunday, December 12, 2010

Predominant Involvement of the Cerebellum in Guinea Pigs Infected with Bovine Spongiform Encephalopathy (BSE)

Journal of Comparative Pathology Article in Press

http://creutzfeldt-jakob-disease.blogspot.com/2010/12/predominant-involvement-of-cerebellum.html


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


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


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/pls/apex/f?p=2400:1001:5492868805159684::NO::F2400_P1001_BACK_PAGE,F2400_P1001_PUB_MAIL_ID:1000,86129



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


Tuesday, November 30, 2010

Council conclusions on the TSE Road Map 2 A Strategy paper on Transmissible Spongiform Encephalopathies for 2010 - 2015

http://transmissiblespongiformencephalopathy.blogspot.com/2010/11/council-conclusions-on-tse-road-map-2.html


Sunday, November 28, 2010

Variably protease-sensitive prionopathy in a PRNP codon 129 heterozygous UK patient with co-existing tau, a synuclein and AB pathology

http://prionopathy.blogspot.com/2010/11/variably-protease-sensitive-prionopathy.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


CHRONIC WASTING DISEASE CWD

http://chronic-wasting-disease.blogspot.com/


Monday, August 9, 2010

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

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

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


Monday, May 12, 2008 BSE YOUNGEST AGE STATISTICS UNDER 30 MONTHS

the myth that cattle under 30 months of age are free from BSE/TSE is just that, a myth, and it's a false myth !

Information released on 2 February 2005 Summary of information requested What statistics are available on cattle less than 30 months of age found to have BSE? Information released VLA has recorded approximately 100 cases of BSE in cattle of 30 months of age or under during the entire period of the BSE epidemic (1986 - 2005). The figure is approximate as for 51 of these the age is only estimated. This is because farmers did not have accurate documentation to confirm birth date. This was not a requirement at the time. We can confirm that of the 100 cases, 49 were under 30 months of age, of these the youngest case was 20 months old.

http://www.defra.gov.uk/vla/vla/vla_ati_020205.htm


Youngest confirmed case 20 Months, Oldest confirmed case 22 Years, Data valid to 01 April 2008

http://www.defra.gov.uk/vla/science/docs/sci_tse_stats_gen.pdf


BSE Youngest and oldest cases by year of onset - GB 20 months, 21 months, (8) 24 months, see complete list of younger than 30 month ;

http://www.food.gov.uk/multimedia/pdfs/otmbsestatistics.pdf


BSE Youngest Japan 21 months, 23 months

http://www.jstage.jst.go.jp/article/ehpm/10/3/130/_pdf


http://bseyoungestage.blogspot.com/


Saturday, December 11, 2010

Species-barrier-independent prion replication in apparently resistant species

http://transmissiblespongiformencephalopathy.blogspot.com/2010/12/species-barrier-independent-prion.html


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


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


Friday, August 20, 2010

Heidenhain Variant of Sporadic Creutzfeldt-Jakob Disease With the Co-Occurrence of Two Different Types of Prion Protein

http://creutzfeldt-jakob-disease.blogspot.com/2010/08/heidenhain-variant-of-sporadic.html


Heidenhain Variant Creutzfeldt Jakob Disease autopsy case report 'MOM'

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

FAX COVER SHEET

DATE: 4-23-98

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

FROM: Gerald Campbell

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

Number of Pages (including cover sheet):

Message:

*CONFIDENTIALITY NOTICE*

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

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

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

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

Autopsy NO.: AU-97-00435

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

FINAL AUTOPSY DIAGNOSIS

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

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


12-14-97 DOD hvCJD confirmed. Happy Anniversary Mom, i'm still here damn't. ...


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

Sunday, December 12, 2010

EFSA reviews BSE/TSE infectivity in small ruminant tissues News Story 2 December 2010

EFSA reviews BSE/TSE infectivity in small ruminant tissues News Story 2 December 2010

EFSA has published today a scientific opinion on Transmissible Spongiform Encephalopathy (TSE)[1] infectivity in the tissues of small ruminants such as goats and sheep[2]. Based on new scientific evidence and taking into account the current situation with respect to the occurrence of TSEs in animals in the EU, EFSA’s Biological Hazards (BIOHAZ) panel has reviewed the distribution of TSE infectivity in small ruminant tissues and has provided for the first time a quantification of the impact of current SRM measures in managing TSE-related risks in small ruminants. The removal of Specified Risk Materials (SRM)[3] such as the brain and spinal cord from animals going into the food chain protects consumers from TSE-related risks. EFSA’s advice will help inform risk managers in the implementation of measures outlined in the TSE Road Map 2[4].

In this opinion, EFSA’s Biological Hazards (BIOHAZ) Panel reviews the latest scientific data on the infectivity of different small ruminant tissues for Classical scrapie, Atypical scrapie and BSE and takes into consideration aspects such as the age and genetic makeup of the animals. With the exception of Bovine Spongiform Encephalopathy (BSE), other TSEs in animals such as scrapie have not been found to be transmissible to humans.

The Panel noted that only one single case[5] of naturally occurring BSE has ever been identified in small ruminants worldwide. Moreover, the opinion provides a set of simulations quantifying for the first time the impact of different SRM options on reducing the risk from the possible presence of BSE in small ruminants. The Panel says that, should a BSE-infected small ruminant ever enter the food chain[6], the current SRM policy would allow a 10-fold reduction of the infectivity load, that is the level of TSE agent present in an infected animal. Experts also advise that the use of the dressed carcass only (excluding the head and the spinal cord) would allow a greater reduction of the BSE exposure risk than the current SRM measures.

With respect to classical scrapie, the panel concludes that, as for BSE, the current SRM policy allows a 10-fold reduction of the infectivity load. The Panel points out that a modification of the SRM list based only on considerations for BSE will also have an impact on human exposure to Classical and Atypical scrapie agents. In addition, the Panel adds that the infectivity of goat kids below 3 months of age is negligible, even if they come from infected herds.

For Atypical scrapie in sheep and goats, the Panel says that since some infectivity, albeit at low levels, can be found in other tissues[7] than those specified in the SRM list, it cannot be assumed that the current SRM measures will prevent the entry of the Atypical scrapie agent into the food chain.

The Panel recommends further improving data collection and risk assessment in this area of work. In particular, it recommends updating this opinion when data from ongoing experiments, such as those concerning the development of BSE in goats, become available. The Panel specifies that the development of specific assessment models could provide a more precise estimate of the impact of SRM removal policies on managing risks from TSEs.

Scientific Opinion on BSE/TSE infectivity in small ruminant tissues

Opinion on TSE Infectivity distribution in ruminant tissues issued by the Scientific Steering Committee (SSC) of the European Commission of 2002 For media enquiries, please contact: Ian Palombi, Press Officer or Steve Pagani, Head of Press Office Tel: +39 0521 036 149 Email: Press@efsa.europa.eu

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

[1] Transmissible Spongiform Encephalopathies (TSEs) are a family of diseases that affect the brain and nervous system of humans and animals. The diseases are characterised by a degeneration of brain tissue giving it a sponge-like appearance. TSEs include Bovine Spongiform Encephalopathy (BSE) principally found in cattle, scrapie in sheep and goats, as well as variant Creutzfeldt Jakob Disease (vCJD) and other diseases in humans. Whilst scrapie (classical and atypical) has been known for centuries as a disease affecting sheep and goats , to date only one single case of naturally occurring BSE has ever been identified in small ruminants. More information on TSEs

[2] This opinion updates a previous opinion on TSE Infectivity distribution in ruminant tissues issued by the Scientific Steering Committee (SSC) of the European Commission of 2002.

[3] Specified risk materials are the tissues containing the highest risk of BSE infectivity. In the EU the removal of SRM, which is the most important public health measure to protect consumers from BSE risk, is mandatory since 2000. Various tissues including the brain, spinal cord, vertebral column, tonsils and ileum are classified and then consequently removed as SRM with specific rules defined by animal species and according to age. The list of SRM is indicated in Annex 5 of Regulation EC 999/2001.

[4] The road map is a strategic document of the European Commission which outlines possible future changes to measures in place in the EU to manage the risk of BSE and other TSEs and ensure a high level of consumer protection. On 16 July 2010 the Commission adopted a Communication to the European Parliament and the Council outlining areas where future possible changes to EU TSE-related measures could be made. The TSE Road Map 2 – A strategy paper on Transmissible Spongiform Encephalopathies for 2010-2015

[5] One goat slaughtered in 2002.

[6] In the EU, sheep and goats found to be infected with TSEs are excluded from the food and feed chain.

[7] Atypical scrapie infectivity can be found for instance in lymphoid tissues, nerves and skeletal muscles.

http://www.efsa.europa.eu/en/press/news/biohaz101202.htm?WT.mc_id=EFSAHL01&emt=1


Scientific Opinion on BSE/TSE infectivity in small ruminant tissues Question number: EFSA-Q-2010-00052

Adopted: 21 October 2010

http://www.efsa.europa.eu/en/scdocs/doc/s1875.pdf


http://www.efsa.europa.eu/en/scdocs/doc/s1875.pdf


please see ;

http://www.goatbse.eu/site/index.php


Scientific Opinion on BSE/TSE infectivity in small ruminant tissues Question number: EFSA-Q-2010-00052 Adopted: 21 October 2010

Summary (0.1 Mb)

Opinion (0.6 Mb)

Summary

Following a request from the European Commission (EC), the Panel on Biological Hazards (BIOHAZ Panel) was asked to deliver a scientific opinion on BSE/TSE infectivity in small ruminant tissues.

The most recent scientific opinion on TSE infectivity distribution in small ruminant tissues was published in January 2002 by the Scientific Steering Committees (SSC) and last amended in November 2002[1]. In recent years new scientific data relating to the infectivity of some tissues in small ruminants became available. Some of those findings related to the tissues from sheep and goats might have an impact to the current measures in relation to the Specified Risk Material (SRM) list of the Regulation (EC) 999/2001[2].

Therefore, the EC asked EFSA: i) to update, as regards small ruminants and on the basis of the most recent scientific data, the SSC scientific opinion from 2002 on TSE infectivity distribution in ruminant tissues; ii) to indicate based on the current epidemiological situation as regards BSE in the small ruminant population in EU, whether a review of the existing SRM list for small ruminants should be envisaged with regard to the potential exposure to the BSE agent.

The BIOHAZ Panel addressed the mandate by reviewing individually for Classical scrapie, BSE and Atypical scrapie in small ruminants aspects related to: i) tissue infectivity distribution according to the age and the genotype of sheep and goats; and ii) the infectious load in the different tissues.

In order to perform the assessment all the currently available scientific results were reviewed. Data about the TSE monitoring in small ruminants in the EU were provided by the European Commission and information on small ruminants slaughtered by species and age category in each EU Member State were provided by the EFSA Focal Points Network.

It was emphasized that this assessment required several assumptions. Moreover, the estimates of the infectious load are based on a simple approach using computations based on a low and a high estimate of each of the parameters. This provides order of magnitude estimates of the infectious load of TSE agents entering into the food chain at EU 27 level. This approach could be replaced by a probabilistic model to provide more insight into the uncertainties. However, due to time and resources constraints it was not possible for the BIOHAZ Panel to develop and validate such a probabilistic model within the framework of this mandate.

Considering Classical scrapie in small ruminants it was concluded that the current SRM policy allows a reduction of the relative infectivity associated to the carcass of an infected animal of about 1 log10 (infectious load as expressed in IC ID50[3] in C57Bl6 mice). The infectivity load as expressed in the opinion (IC ID50 in C57Bl6 mice) cannot be related to any quantifiable dietary transmission risk in farmed animals or humans.

As regards to Classical scrapie in goats, it was further concluded that, according to the currently available knowledge, goat kids below 3 months of age, even coming from infected herds, represent a negligible source of infectivity for the food chain.

On the basis of data collected between 2007 and 2009, the total number of Classical scrapie infected animals that could enter yearly into the food chain in the EU27 as a whole was estimated to approximately range between 16,000 and 67,000 (most probable estimate 29, 000) for sheep and between 10,000 and 34,000 (most probable estimate 13,000) for goats.

The Panel pointed out that Classical scrapie is present in a majority of EU member states. However because differences in the prevalence of the disease, population size and production system (age at slaughter), there are significant differences between certain member states with regards to Classical scrapie infectivity load that may enter the food chain. This heterogeneity and the differences in consumption pattern between countries and regions mean that the dietary exposure to Classical scrapie cannot be considered to be homogeneous in the EU27.

It was furthermore concluded that at the EU27 level, the current SRM policy in force allows a global reduction of the potential exposure to Classical scrapie which can be estimated to be around 1 log10 (infectious load as expressed in IC ID50 in C57Bl6 mice).

When considering BSE in small ruminants, the Panel concluded that with 95% confidence the the number of BSE cases that could enter yearly into the food chain in the EU is ranging between 0 and 240 for sheep and between 0 and 381 for goats. This estimate argues against any current widespread BSE epidemic within the EU small ruminant population.

The BIOHAZ Panel indicated that the current SRM policy allows a reduction of the relative infectivity associated to the carcass of a BSE infected animal of about 1 log10 (infectious load as expressed in IC ID50 in C57Bl6 mice). The infectivity load as expressed in the opinion (IC ID50 in C57Bl6 mice) cannot be related to any quantifiable dietary transmission risk in farmed animals or humans.

It was further emphasized that preliminary biochemical and immunohistochemical data in goats suggest that there might be no major involvement of the lymphoid tissues in preclinical and clinical phase of the disease after oral experimental challenge. Before more complete information becomes available it is not possible to provide reliable specific estimates of the impact of SRM removal measures on the BSE exposure that would be associated with an infected goat entering into the food chain. The Panel highlighted that in this context the estimates of the impact of SRM removal measures on the BSE exposure provided for BSE in sheep could be considered as a worst case scenario for BSE in goats.

As regards to Atypical scrapie both in sheep and goats it was concluded that low levels of infectivity can be present in peripheral tissues (lymphoid tissues, nerves, skeletal muscle) in preclinical and clinical cases of Atypical scrapie harbouring various genotypes. Consequently SRM measures cannot be assumed to prevent the entry of the Atypical scrapie agent into the food chain.

It was highlighted that there is currently no data on the kinetics of distribution of the Atypical scrapie agent into peripheral tissues of incubating small ruminants and that there are uncertainties on the Atypical scrapie pathogenesis and its true prevalence in the EU small ruminant population. Therefore, the Panel was not in position to provide an assessment of the current Atypical scrapie infectious load entering into the food chain.

In answering to the first Term of Reference, the BIOHAZ Panel revised the TSE tissue infectivity distribution in small ruminants and provided updated information within the body of the opinion (section 2, tables 1 to 12).

Considering the second Term of Reference, the BIOHAZ Panel provided a set of simulations illustrating the impact of different policy options on the BSE infectious load potentially present in an infected sheep. According to these simulations, the use of the dressed carcass[4] only would allow a greater reduction of the BSE exposure risk than the current SRM policy measures. The elimination of the ileum has a major impact on the relative reduction of the BSE infectivity load that might enter in the food chain from an animal aged below 12 months. The CNS (Central Nervous System) removal is the most efficient measure to reduce the relative infectivity load associated with a BSE infected small ruminant older than 12 months entering into the food chain.

It was finally indicated that a modification of the SRM list driven only by consideration about BSE will also impact on the dietary exposure to Classical scrapie and Atypical scrapie agents.

The BIOHAZ Panel recommended: i) to update the assessment once data from ongoing experiments will become available; ii) to develop a specific probabilistic model in order to provide more precise estimates of the impact of SRM removal on the infectious load of TSE agents entering into the food chain at EU 27 level; iii) to improve the quality of the data collected on the small ruminant population (e.g. age category and destination of the animal); and iv) to expand the current data collected in the context of the TSE surveillance activities by recording the tested animal age category and the type of rapid test used.

Published: 2 December 2010

http://www.efsa.europa.eu/en/scdocs/scdoc/1875.htm


http://www.efsa.europa.eu/en/scdocs/doc/s1875.pdf


3.2.1. Conclusions • According to the model developed by EFSA in its opinion of January 2007 the maximum number of BSE cases in the EU27 sheep population is equal to or below 4.2 per million sheep with a most probable value of 0, under the assumption of a 50% sensitivity of the screening test. • According to the model developed by EFSA in its opinion of January 2007 the maximum number of BSE cases in the EU27 goat population is equal to or below 53.7 per million goats with a most probable value of 14.7, under the assumption of a 50% sensitivity of the screening test. • There are uncertainties related to the technical limits of the methodology applied to detect BSE in sheep (discriminatory assay).

snip...

2.3. BSE

BSE agent possible spread in small ruminants has been considered as a major threat over the last 15

years.

To date, there has been:

• no report of naturally occurring BSE in sheep in the commercial situation,

• one confirmed case of natural BSE in a goat was reported in France 2002 (Eloit et al., 2005).

Both sheep and goats have been shown to be susceptible to the BSE agent and in the absence of natural cases to be studied, all the knowledge related to BSE pathogenesis in small ruminants relies on experimental challenges in sheep (Bellworthy et al., 2008; Bellworthy et al., 2005b; Gonzalez et al., 2005; Jeffrey et al., 2001b; van Keulen et al., 2008a) and goats EU “goatBSE project (FOOD-CT-2006-36353)8.

Like the situation in natural scrapie, PRNP polymorphisms have a major impact on BSE susceptibility and dissemination of the agent in the organs. However, PRNP genotypes that are associated with the highest susceptibility in the context of BSE in sheep are different from those observed for natural scrapie. Moreover it is now well documented that BSE agent can propagate in sheep bearing the ARR/ARR genotype after oral exposure (Andreoletti et al., 2006; Lantier et al., 2008).

The low natural prevalence of BSE in a number of species (including human) other than cattle that were exposed to cattle BSE suggests the existence of real barrier to transmission of this disease under natural conditions. However, recently the BSE agent in sheep was described to harbour a higher virulence and capacities to cross the transmission barrier than the original BSE cattle agent (Espinosa et al., 2007; Espinosa et al., 2009). These observations suggest that exposure to small ruminant passaged BSE agent might result in a higher transmission rate in a third species compared to that observed with cattle BSE.

8 Details available at http://www.goatbse.eu


BSE/TSE infectivity in small ruminant tissues

EFSA Journal 2010;8(11):1875 26

Recently presented data suggest that BSE adapted in small ruminants might have a higher efficacy to cross the human species barrier (as modelled in transgenic mice expressing the human PrP Met 129 gene) than cattle BSE (Plinstone et al., 2010). Currently the minimum BSE infectious dose that would allow to infect a human being remains unknown.

2.3.1. BSE in sheep

The distribution of PrPSc in sheep experimentally infected with BSE is very similar to that observed in sheep with Classical scrapie. It involves the lymphoreticular system, the peripheral nervous system, enteric nervous system, muscle, blood and Central nervous system (Foster et al., 1993; Jeffrey et al., 2001b; van Keulen et al., 2008b). More recently scant PrPSc deposits have been detected in the liver of clinical and preclinical and ARQ/ARQ BSE (Everest et al., 2009), which is consistent with earliest report of infectivity presence in this tissue (Bellworthy et al., 2005b).

The presence of PrPSc was described in lymphoreticular tissues from sheep clinically affected with ARR/ARR and VRQ/VRQ genotype (Andreoletti et al., 2006; Bellworthy et al., 2008) although with greatly prolonged incubation periods compared to ARQ/ARQ or AHQ/AHQ sheep. Together studies published by (Bellworthy et al., 2005b; van Keulen et al., 2008a) and the data presented by Lantier et al. (Lantier et al., 2008) provides an overall picture of the dissemination kinetics of the BSE agent in the organs of orally challenged ARQ/ARQ sheep (see Table 11).

snip...

2.3.2. BSE in goats

Until recently, there was no specific data describing the pathogenesis of the BSE agent following oral exposure of goats. In that context, BSE risk assessments undertaken so far in that species have relied on the assumption that BSE in goats would behave similarly to natural scrapie in goats and experimental BSE in sheep (EFSA, 2005a).

Within the framework of the European GoatBSE project (FOOD-CT-2006-36353; www.goatBSE.eu), oral challenge experiments of BSE to goats were performed using either cattle BSE isolate or experimental goat BSE isolate (INRA; the University of Edinburgh; Friedrich-Loeffler Institute).

Animals harbouring various PRNP genotypes were inoculated; the (expected) susceptible wild-type I142R211Q222/IRQ, the animals with lower susceptibility genotypes I142Q211Q222/IRQ, I142R211K222/IRQ and M142R211Q222/IRQ were used (EFSA Panel on Biological Hazards (BIOHAZ), 2009).

BSE/TSE infectivity in small ruminant tissues

EFSA Journal 2010;8(11):1875 29

Serial kills of a defined number of animals were performed at 6 and 12 and 24 months post infection. To date, PrPSc was detected in the brainstem (PTA-immunoblot and imunohistochemistry) of four wild-type goats 24 months post infection, which indicates a BSE-infection.

Additionally in these animals PrPSc deposition (Immunohistochemistry) was found in the gut (GALT) and the peripheral nervous system of the time point killed animals, but not in other lymphoid tissues.

These PrPSc detection results (Immunohistochemistry) are consistent with a lack of major involvement of the lymphoreticular tissues. In order to confirm these results, a panel of relevant tissues are currently being tested by bioassay ovine PrP overexpressing mice (TgshpXV).

In the meanwhile available results remain too preliminary to draw definitive conclusions. However, if confirmed, they would signify that BSE pathogenesis in sheep and goats might be dissimilar. Under such scenario the use of data collected in sheep infected with BSE could not anymore be considered pertinent to assess BSE risk in goat, other than to assume that extrapolating from sheep data would give a worst case scenario.

2.3.3. BSE conclusions

• In sheep:

Dissemination and distribution of PrPSc in the organs of orally challenged sheep bearing the ARQ/ARQ genotype is well documented.

The kinetics of distribution of the BSE agent in sheep harbouring other genotypes is less or not documented.

There is little information available on the infectivity titer in the tissues of BSE affected sheep at the different stages of the disease.

• In goats:

Preliminary data, after oral experimental challenge, suggest that there is apparently no major involvement of the lymphoid tissues in the preclinical and clinical phase. However, these data need to be completed and confirmed.

Pathogenesis data collected in sheep can be considered as a worst case scenario for BSE in goats.

There is no information available on the infectivity titer in the tissues of BSE affected goats at the different stages of the disease.

snip...

http://www.efsa.europa.eu/en/scdocs/doc/1875.pdf


SCIENTIFIC OPINION

Scientific Opinion on BSE/TSE infectivity in small ruminant tissues1

EFSA Panel on Biological Hazards (BIOHAZ)2, 3

European Food Safety Authority (EFSA), Parma, Italy

ABSTRACT

The objectives addressed were i) to provide an update on TSE (Transmissible Spongiform Encephalopathy) infectivity distribution in small ruminant tissues; and ii) to indicate based on the current epidemiological situation as regards to BSE (Bovine Spongiform Encephalopathy) in the small ruminant population in the EU (European Union), whether a review of the existing SRM (Specified Risk Materials) list for small ruminants should be envisaged with regard to the potential exposure to the BSE agent. The appraisal was addressed by reviewing for Classical scrapie, BSE and Atypical scrapie in small ruminants aspects related to: i) tissue infectivity distribution according to the age and the genotype of sheep and goats; and ii) the infectious load in the different tissues. In order to perform the assessment all the currently available scientific results were reviewed, and data on TSE monitoring in small ruminants in the EU and on small ruminants slaughtered by species and age category in each EU Member State were considered. The reduction of the infectivity associated to the carcass of an infected individual achieved by the current SRM policy in small ruminants for Classical scrapie and BSE was estimated. The total number of Classical scrapie infected sheep and goats that could enter yearly into the food chain was provided. Moreover, considerations about Atypical scrapie were given. A set of simulations allowing estimating the impact of different policy options on the BSE infectious load potentially present in an infected sheep was provided.

© European Food Safety Authority, 2010

KEY WORDS

Bovine Spongiform Encephalopathy (BSE), Classical scrapie, Atypical scrapie, Transmissible Spongiform Encephalopathies (TSEs), Specified Risk Material (SRM), Small Ruminants

snip...

When considering BSE in small ruminants, the Panel concluded that with 95% confidence the the number of BSE cases that could enter yearly into the food chain in the EU is ranging between 0 and 240 for sheep and between 0 and 381 for goats. This estimate argues against any current widespread BSE epidemic within the EU small ruminant population.

http://www.goatbse.eu/site/images/stories/diverse/opinion%20on%20bse-tse%20infectivity%20in%20sruminants.pdf


BSE has been detected in two goats. One case was a French goat which was born in 2000 and died in 2002. The second was a British goat which was born in 1987 and died in 1990.

http://www.defra.gov.uk/foodfarm/farmanimal/diseases/atoz/bse/othertses/scrapie/


http://www.defra.gov.uk/foodfarm/farmanimal/diseases/atoz/bse/science-research/sheep-goats/experimental.htm


http://www.defra.gov.uk/foodfarm/farmanimal/diseases/atoz/bse/science-research/projects-table.htm#3d


http://www.defra.gov.uk/foodfarm/farmanimal/diseases/atoz/bse/science-research/documents/bse-sheep-goats.pdf


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


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


4.2.9 A further hypothesis to explain the occurrence of BSE is the emergence or selection of a strain or strains of the scrapie agent pathogenic for cattle. Mutations of the scrapie agent. which can occur after a single passage in mice. have been well documented (9). This phenomenon cannot be dismissed for BSE. but given the form of the epidemic and the geographically widespread occurrence of BSE, such a hypothesis" would require the emergence of a mutant scrapie strain simultaneously in a large . number of sheep flocks, or cattle. throughout the country. Also. if it resulted "from a localised chance transmission of the scrapie strain from sheep to cattle giving rise , . to a mutant. a different pattern of disease would have been expected: its range would '. have increased with time. Thus the evidence from Britain is against the disease being due to a new strain of the agent, but we note that in the United States from 1984 to 1988 outbreaks of scrapie in sheep flocks are reported to have Increased markedly. now being nearly 3 times as high as during any previous period (18).

http://collections.europarchive.org/tna/20080102132706/http://www.bseinquiry.gov.uk/files/ib/ibd1/tab02.pdf


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

http://scrapie-usa.blogspot.com/2007/12/scrapie-hb-parry-seriously-yb886841.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


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



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


PR-26

NOR98 SHOWS MOLECULAR FEATURES REMINISCENT OF GSS

R. Nonno1, E. Esposito1, G. Vaccari1, E. Bandino2, M. Conte1, B. Chiappini1, S. Marcon1, M. Di Bari1, S.L. Benestad3, U. Agrimi1 1 Istituto Superiore di Sanità, Department of Food Safety and Veterinary Public Health, Rome, Italy (romolo.nonno@iss.it); 2 Istituto Zooprofilattico della Sardegna, Sassari, Italy; 3 National Veterinary Institute, Department of Pathology, Oslo, Norway

Molecular variants of PrPSc are being increasingly investigated in sheep scrapie and are generally referred to as “atypical” scrapie, as opposed to “classical scrapie”. Among the atypical group, Nor98 seems to be the best identified. We studied the molecular properties of Italian and Norwegian Nor98 samples by WB analysis of brain homogenates, either untreated, digested with different concentrations of proteinase K, or subjected to enzymatic deglycosylation. The identity of PrP fragments was inferred by means of antibodies spanning the full PrP sequence. We found that undigested brain homogenates contain a Nor98-specific PrP fragment migrating at 11 kDa (PrP11), truncated at both the C-terminus and the N-terminus, and not N-glycosylated. After mild PK digestion, Nor98 displayed full-length PrP (FL-PrP) and N-glycosylated C-terminal fragments (CTF), along with increased levels of PrP11. Proteinase K digestion curves (0,006-6,4 mg/ml) showed that FL-PrP and CTF are mainly digested above 0,01 mg/ml, while PrP11 is not entirely digested even at the highest concentrations, similarly to PrP27-30 associated with classical scrapie. Above 0,2 mg/ml PK, most Nor98 samples showed only PrP11 and a fragment of 17 kDa with the same properties of PrP11, that was tentatively identified as a dimer of PrP11. Detergent solubility studies showed that PrP11 is insoluble in 2% sodium laurylsorcosine and is mainly produced from detergentsoluble, full-length PrPSc. Furthermore, among Italian scrapie isolates, we found that a sample with molecular and pathological properties consistent with Nor98 showed plaque-like deposits of PrPSc in the thalamus when the brain was analysed by PrPSc immunohistochemistry. Taken together, our results show that the distinctive pathological feature of Nor98 is a PrP fragment spanning amino acids ~ 90-155. This fragment is produced by successive N-terminal and C-terminal cleavages from a full-length and largely detergent-soluble PrPSc, is produced in vivo and is extremely resistant to PK digestion. Intriguingly, these conclusions suggest that some pathological features of Nor98 are reminiscent of Gerstmann-Sträussler-Scheinker disease.

119

http://www.neuroprion.com/pdf_docs/conferences/prion2006/abstract_book.pdf


P03.141

Aspects of the Cerebellar Neuropathology in Nor98

Gavier-Widén, D1; Benestad, SL2; Ottander, L1; Westergren, E1 1National Veterinary Insitute, Sweden; 2National Veterinary Institute,

Norway Nor98 is a prion disease of old sheep and goats. This atypical form of scrapie was first described in Norway in 1998. Several features of Nor98 were shown to be different from classical scrapie including the distribution of disease associated prion protein (PrPd) accumulation in the brain. The cerebellum is generally the most affected brain area in Nor98. The study here presented aimed at adding information on the neuropathology in the cerebellum of Nor98 naturally affected sheep of various genotypes in Sweden and Norway. A panel of histochemical and immunohistochemical (IHC) stainings such as IHC for PrPd, synaptophysin, glial fibrillary acidic protein, amyloid, and cell markers for phagocytic cells were conducted. The type of histological lesions and tissue reactions were evaluated. The types of PrPd deposition were characterized. The cerebellar cortex was regularly affected, even though there was a variation in the severity of the lesions from case to case. Neuropil vacuolation was more marked in the molecular layer, but affected also the granular cell layer. There was a loss of granule cells. Punctate deposition of PrPd was characteristic. It was morphologically and in distribution identical with that of synaptophysin, suggesting that PrPd accumulates in the synaptic structures. PrPd was also observed in the granule cell layer and in the white matter. The pathology features of Nor98 in the cerebellum of the affected sheep showed similarities with those of sporadic Creutzfeldt-Jakob disease in humans.

http://www.neuroprion.com/pdf_docs/conferences/prion2007/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


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

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


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.

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


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

NATUREVol 45726 February 2009

http://www.nature.com/nature/journal/v457/n7233/full/4571079b.html


Thursday, October 07, 2010

Experimental Transmission of H-type Bovine Spongiform Encephalopathy to Bovinized Transgenic Mice

http://bse-atypical.blogspot.com/2010/10/experimental-transmission-of-h-type.html


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

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


Rare BSE mutation raises concerns over risks to public health

SIR — Atypical forms (known as H- and L-type) of bovine spongiform encephalopathy (BSE) have recently appeared in several European countries as well as in Japan, Canada and the United States. This raises the unwelcome possibility that variant Creutzfeldt–Jakob disease (vCJD) could increase in the human population. Of the atypical BSE cases tested so far, a mutation in the prion protein gene (PRNP) has been detected in just one, a cow in Alabama with BSE;

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


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


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


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


Saturday, December 11, 2010

Species-barrier-independent prion replication in apparently resistant species

http://transmissiblespongiformencephalopathy.blogspot.com/2010/12/species-barrier-independent-prion.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


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


Sunday, March 28, 2010

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

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


TSS