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From: TSS ()
Subject: EU TO GIVE REALITY CHECK NEXT MONTH ON RISK FACTORS FOR HUMAN HEALTH VIA SHEEP AND GOAT FROM BSE AKA MAD COW DISEASE
Date: October 19, 2006 at 9:05 am PST

EU TO GIVE REALITY CHECK NEXT MONTH ON RISK FACTORS FOR HUMAN HEALTH VIA SHEEP AND GOAT FROM BSE AKA MAD COW DISEASE (all the while ignoring the real risk factors from sheep and goat scrapie to humans)


EU will comment on human risk from prion disease
Thu Oct 19, 2006 3:54 AM BST


BRUSSELS (Reuters) - Europe's top food safety agency will give its views next month on whether a fatal brain-wasting disease, similar to mad cow disease, might threaten human health if transmitted form sheep and goats, its executive director said on Wednesday.

Earlier this year, two sheep in France and one in Cyprus, were suspected of being infected with bovine spongiform encephalopathy (BSE) infection, also known as mad cow disease. A final series of tests is continuing and should be completed next year.

The sheep were initially tested for scrapie, which is similar to BSE, and known to exist in sheep for more than 100 years.

That followed on from a similar ordeal that France faced in 2005, when mad cow disease was confirmed in a goat that had been killed three years earlier --- the first case of BSE in a goat.

Scrapie belongs to a family of diseases known as TSEs (transmissible spongiform encephalopathy) and characterised by a degeneration of brain tissue giving a sponge-like appearance.

The group includes Creutzfeldt Jakob Disease in humans and BSE in cattle. These fatal diseases, caused by nervous system proteins called prions, gradually destroy the brain.

"At the beginning of November, we will deliver an overview of the TSE situation with regard to the possible presence of this disease and its transmission to humans via sheep and goats," Catherine Geslain-Laneelle, executive director of the European Food Safety Authority (EFSA) told reporters.

"We have worked closely with France and have received their (food safety authority's) opinion. That's being examined this week and will be addressed in our final opinion in November."

While no case of BSE has ever been confirmed as naturally occurring in sheep, there are fears that some sheep diagnosed as having scrapie -- not known to be harmful to humans -- might be carrying the other brain-wasting disease.

Since the late 1990s, the EU has extensively monitored and checked for scrapie and BSE in cattle, sheep and goats. Given the widespread testing, isolated cases of BSE may be found but this should not indicate a major problem, EU officials say.

http://today.reuters.co.uk/news/articlenews.aspx?type=scienceNews&storyID=2006-10-19T025431Z_01_KNE910424_RTRIDST_0_SCIENCE-EU-PRION-DISEASE-DC.XML

SCRAPIE TRANSMITS TO PRIMATES BY THERE NON-FORCED ORAL CONSUMPTION

SCRAPIE TRANSMISSION STUDIES AND SURVEILLANCE OF SCRAPIE (CJD) TO HUMANS HAVE NEVER BEEN CONDUCTED

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://www.bseinquiry.gov.uk/files/yb/1976/10/12004001.pdf


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.


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

Research Project: OVINE PRION & VIRAL INFECTIONS: SCRAPIE & OVINE PROGRESSIVE PNEUMONIA, DIAGNOSIS & CONTROL
Location: Animal Diseases Research


2005 Annual Report

1.What major problem or issue is being resolved and how are you resolving it (summarize project aims and objectives)? How serious is the problem? What does it matter?
The economic losses to the sheep industry due to ovine scrapie can be reduced by a coordinated program of live animal testing, replacement with sheep of lower susceptibility, and reducing transmission within the flock. Scrapie is a transmissible spongiform encephalopathy associated with deposition of an abnormal isoform of a mammalian glycoprotein, the prion protein, in tissues throughout the sheep. The highest level of accumulation is in the brain, although detectable levels are found in lymphoid tissues and placenta/fetal tissues. Detection of prions in peripheral lymphoid tissue can be used to identify and cull infected animals early in infection. Further, the susceptibility of sheep to clinical scrapie and to accumulation of prions is under genetic control. Quantitative determination of the level of protection associated with commonly occurring genotypes could enable producers and regulatory programs to integrate protective genetics with elimination of infected stock to reduce the amount of disease in U.S. flocks. Control of all domestic prion diseases is important in reducing trade barriers for U.S. sheep and germplasm and for assuring the present and future global markets for cattle. Ovine progressive pneumonia virus causes persistent viral infection and development of multi-organ inflammatory disease in some animals. The infection rates in US sheep flocks range from 9 to 49%. A variable and unpredictable percentage of infected animals will progress to clinical disease with high viral titers and increased risk of transmission to flockmates. This project has produced a serologic test for the disease. The current project includes development of a vaccine to reduce infected animals and identification of genes associated with decreased transmission in infected sheep. Sheep scrapie is a member of a group of diseases that includes bovine spongiform encephalopathy (BSE). Sheep scrapie is associated with minor direct losses to the industry. However, loss of international markets for sheep and sheep germplasm and loss of the domestic access to rendering facilities are major economic losses to the industry. Control programs based on epidemiology alone have failed to control the spread of scrapie throughout the U.S. since the disease was introduced in 1947. A control program based on a live animal diagnostic test supplemented by introduction of replacement stock of lower genetic susceptibility is urgently needed. Transmission barriers of these diseases are not understood. Therefore, the presence of any of these diseases within the U.S. represents a continuous threat for emergence in animals not yet found to have been infected in the U.S. The occurrence of BSE in U.S. cattle has caused economic losses in the U.S. cattle domestic market and the world markets. Animals with clinical signs of ovine progressive pneumonia virus represent the main risk of virus transmission because disease progression is associated with much higher virus loads than is nonprogressive persistent infection. Therefore, the immunogenetic basis of disease pathogenesis is an important consideration in SRLV research. The most significant problem associated with SRLV infection is the inability to determine which animals will progress to severe clinical disease and death. Our objectives are to reduce the clinical disease rates and viremia levels through a vaccination program targeting the type 1 immune responses and to determine the immunogenetics associated with this response. SRLV research will lead to methods for the induction of immunologic control and genetic predictors of animals with a low potential for transmission if infected. Our research concerning the transmissible encephalopathies and small ruminant lentiviruses address the following elements of our National Program in Animal Production, Product Value and Safety. Our research encompasses the National Program Initiative 103 Animal Health at 100%, and our research components include pathogen detection and diagnostics, animal immunology, mechanism of disease, genetic resistance to disease, and strategies to control infectious and non-infectious diseases.

2.List the milestones (indicators of progress) from your Project Plan.
Year 1 (FY2002)

Validate diagnostic and genetic tests; IHC test validation studies and PrP genotype continue from previous CRIS.

Define transmission route. Continue study on effect of maternal disease status and fetal genotype of PrP-Sc in placenta. Initiate studies on effect of pregnancy and placenta on PrP-Sc.

Initiate blood transfusion study. Complete methods for detecting and quantitating PrP-C and PrP-Sc in dissociated lymph nodes.

Induce type 1 response to CAEV and MVV. Immunize goats with plasmid DNA expressing CAEV env and boost with SU-FIA. Isolate and characterize wild type CAEV for challenge and challenge-immunized goats.

Identify MVV resistant MHC class II haplotypes. Complete titration and isotypes of antibodies from Dubois sheep.

Year 2 (FY2003)

Continue validation of IHC tests.

Continue studies on effect of pregnancy and placenta on PrP-Sc.

Continue FACS and IHC analysis of lymph node cells for PrP-C and PrP-Sc.

Continue examination of postchallenge parameters. Construct and characterize a recombinant plasmid expressing MVV8534 env.

Complete T cell proliferation assays and divide sheep.

Year 3 (FY2004)

Complete validation of IHC tests.

Complete studies on effect of pregnancy and placenta on PrP-Sc.

Complete FACS and IHC analysis of lymph node cells for PrP-C and PrP-Sc.

Continue examination of postchallenge parameters. Construct and characterize a recombinant plasmid expressing MVV8534 env.

Year 4 (FY2005)

Initiate studies on rapid, high volume diagnostic testing; complete PrP genotype study.

Complete study on effect of maternal disease status and fetal genotype of PrP-Sc in placenta Initiate studies on regulation of PrP-C by estrous cycle and pregnancy.

Complete PrP-C distribution and quantitation in peripheral blood cells; initiate immunomagnetic bead enrichment studies if indicated.

Immunize sheep with plasmid DNA expressing MVV8534 env and boost with MVV SU-FIA. Challenge immunized goats with MVV8534.

Complete PCR-RFLP of OvLa DRB-1 alleles.

Year 5 (FY2006)

Complete PrP-Sc rapid test development and transfer technology.

Complete studies on regulation of PrP-C by estrous cycle and pregnancy.

Complete blood transfusion study.

Continue examination of postchallenge parameters.

Identify OvLa DRB-1 alleles that associate with type 1 responses. Identify MMV-free sheep with appropriate DRB-1 haplotypes and challenge with MVV8534.


3a.List the milestones that were scheduled to be addressed in FY 2005. For each milestone, indicate the status: fully met, substantially met, or not met. If not met, why.

Initiate studies on rapid, high volume diagnostic testing; complete PrP genotype study.
Milestone Substantially Met

Complete study on effect of maternal disease status and fetal genotype of PrP-Sc in placenta Initiate studies on regulation of PrP-C by estrous cycle and pregnancy.
Milestone Substantially Met

Complete PrP-C distribution and quantitation in peripheral blood cells; initiate immunomagnetic bead enrichment studies if indicated.
Milestone Fully Met

Immunize sheep with plasmid DNA expressing MVV8534 env and boost with MVV SU-FIA. Challenge immunized sheep with MVV8534.
Milestone Not Met

Complete PCR-RFLP of OvLa DRB-1 alleles.
Milestone Fully Met


3b.List the milestones that you expect to address over the next 3 years (FY 2006, 2007, and 2008). What do you expect to accomplish, year by year, over the next 3 years under each milestone?
Year 5, 6 and 7 milestones are listed below with a description of the anticipated outcomes. The entire project will be completed during FY 2006, and a new project will be developed to undergo OSQR review, and subsequent implementation beginning FY 2007.

Year 5 (FY2006)

Complete rapid scrapie test development and transfer technology.

Complete PrP genotype study in goats.

Complete sequencing of expressed OvLa MHC Class II DRB-1 alleles.

Continue oral scrapie transmission study in goats.

Potential impact: A rapid test for scrapie will facilitate diagnosis. A map of the PrP gene and the mutations for goats will aid in determining if certain genotypes are more susceptible or resistant to scrapie once challenge experiments are initiated. Characterization of the expressed OvLa MHC Class II DRB1 alleles will allow development of a rapid high-throughput system for typing sheep.

Year 6 (FY 2007)

Continue oral scrapie transmission study in goats.

Initiate experimental inoculation of OPPV into sheep with specific OvLa MHC Class II DRB-1 expressed alleles.

Develop rapid MHC Class II DRB1-1 typing tests.

Potential impact: Data on oral transmission of scrapie to goats will aid in determining the impact of goats on scrapie transmission to sheep flocks in the US. Development of a rapid MHC Class II DRB1 typing test will allow rapid screening of sheep for specific MHC Class II types followed by experimental inoculation of OPPV.

Year 7 (FY 2008)

Continue experimental inoculation of OPPV into sheep with specific OvLa MHC Class II DRB-1 expressed alleles.

Initiate TSE strain studies.

Complete oral scrapie transmission study in goats.

Potential impact: Examining strains of scrapie will aid in understanding transmission of sheep scrapie. Data on oral transmission of scrapie to goats will aid in determining the impact of goats on scrapie transmission to sheep flocks in the US. Monitoring of experimental inoculation of OPPV into sheep with specific MHC Class II DRB1 types will allow associations to be made between disease progression and specific MHC Class II DRB1 types.


4a.What was the single most significant accomplishment this past year?
We found that multiple fetuses in the uterus of a pregnant ewe have an effect on PrPSc accumulation in the placental tissue. We previously showed that if a sheep fetus has a scrapie-resistant genotype, PrPSc does not accumulate in the placenta tissue of scrapie-infected ewes. We have now found, however, the placenta tissue associated with a fetus of a scrapie-resistant genotype can accumulate PrPSc if it is positioned next to a fetus of a scrapie susceptible genotype in utero in scrapie infected ewes. This has potential impact to the sheep industry in relying on the genetics to breed for resistance to scrapie.


4b.List other significant accomplishments, if any.
When applying OPPV diagnostic tests to the field, it is necessary to identify the immunodominant antigen in OPPV-infected sheep. One publication has resulted from identifying the surface envelope glycoprotein (SU) as the B-lymphocyte immunodominant antigen in mature OPPV-infected sheep. Because the CAEV cELISA detects anti-SU antibodies, this result ensures that most mature OPPV-infected sheep will have measurable titers of anti-SU antibodies which can be detected in the CAEV cELISA This result has direct implications for the sheep industry in terms of accurate OPPV diagnostic testing using the CAEV cELISA.

Previous studies have shown that sheep with Prnp diploid genotypes of AA, QR and AA, RR at codons 136, 171, respectively, are more resistant to scrapie. However, it is unknown whether breeding toward these scrapie-resistant Prnp diploid genotypes would affect lamb production traits. ADRU is currently collaborating with University of Wyoming (5348-32000-019-03S) to show that breeding flocks toward the scrapie resistant PrP genotypes does not influence lamb production. Results of this research have yielded one publication and has impact on the sheep industry.

We previously showed that if a sheep fetus has a scrapie-resistant genotype, PrPSc does not accumulate in the placenta tissue of scrapie-infected ewes. Another question we wanted to address, which relates to sheep with scrapie-resistant Prnp diploid genotypes, is whether ewes with scrapie resistant PrP genotypes born from scrapie-infected ewes will accumulate PrPSc in their placental tissue after being bred back to a ram with a scrapie susceptible PrP genotype. In addition, ADRU and North Dakota State University (5348-32000-019-04S) are collaborating to evaluate the natural passage of scrapie through a flock with Prnp diploid genotypes at 136 of AV and VV. Since this flock is the first documented case of valine 136-based scrapie in the U.S., it is extremely important to understand the Prnp genetics of all flock mates and the transmission of valine 136-based scrapie.

4c.List any significant activities that support special target populations.
None.


4d.Progress report.
None


5.Describe the major accomplishments over the life of the project, including their predicted or actual impact.
A practical live animal test for scrapie and preclinical postmortem tests for scrapie were developed and transferred to the regulatory agencies for use in the US. Monoclonal antibodies useful in assays on routinely formalin fixed tissue from infected sheep, deer, elk, cattle, humans, mink, domestic cats and a wide variety of captive wildlife potentially exposed to prion diseases were developed. Mechanisms for preventing transmission of scrapie through genetic selection of sires were demonstrated. Along with sire testing, genetic testing in bred ewes will ensure less transmission of scrapie from ewe to lamb.

The specific immune cells in lymph nodes involved in PrPSc accumulation remain unknown. Therefore, we analyzed lymph nodes for the presence of PrPSc and macrophage or follicular dendritic cell (FDC) markers using dual immunohistochemistry. Results indicated that lymph node follicular macrophages acquire PrPSc by phagocytosis of CD21+ FDC processes and process full-length PrPSc to N-terminally truncated PrPSc. These data provide the first knowledge in determining the pathogenesis of sheep scrapie in FDC and macrophages.

A new caprine arthritis-encephalitis virus (CAEV) competitive inhibition enzyme-linked immunosorbent assay (cELISA) had previously been developed. We tested 200 goat sera for the presence of CAEV antibodies using cELISA against the standard of comparison, immunoprecipitations (IP) of [S35] methionine-labeled CAEV lysate. The CAEV cELISA validation resulted in 100% sensitivity and 96.4% specificity against the standard of comparison. By annually testing goats for CAEV using cELISA, a CAEV-free herd could be established.

Because of the high sensitivity and specificity of the CAEV cELISA in goats, validation of the CAEV cELISA in sheep also ensued. By using IP of [S35] methionine-labeled OPPV lysate as the comparable standard, detection of serum antibodies to ovine progressive pneumonia virus (OPPV) in sheep using the CAEV cELISA yielded a sensitivity 98.6% and a specificity of 96.9%. This indicates that one diagnostic test, the CAEV cELISA, can be utilized for detection of small ruminant lentiviruses.

When applying the CAEV cELISA diagnostic test to the field, it is necessary to identify OPPV field strains. We isolated 7 new OPPV field strains from the colostrum cells of 10 OPPV-infected sheep. We characterized and compared the surface envelope glycoprotein (SU) deduced amino acid sequences from these sheep against previously characterized OPPV, CAEV and maedi-visna virus strains. The new OPPV field strains had high sequence identity to OPPV and CAEV strains more than MVV strains. This result is important for future CAEV cELISA testing of U.S. sheep and sheep outside the U.S. infected with OPPV or MVV, respectively.

Standardized, validated diagnostic tests are needed for eradication of scrapie. In FY2001-FY2003, a cooperative ARS-APHIS-state test validation program resulted in submission of samples from more than 2,000 sheep. These samples are being used to validate the third eyelid live animal test, the postmortem immunohistochemistry test, and to develop novel rapid, high throughput tests suitable for slaughter surveillance. A panel of internationally accepted tests suitable for diagnostic and surveillance purposes will result.

Control of scrapie and the small ruminant lentiviruses (SRLV) directly benefits small farms that raise sheep and goats for supplementary income. Direct and indirect losses to these producers because of these diseases are significant. Control programs that include identification of infected flocks and animals should reduce the economic consequences of SRLV and prion diseases.


6.What science and/or technologies have been transferred and to whom? When is the science and/or technology likely to become available to the end-user (industry, farmer, other scientists)? What are the constraints, if known, to the adoption and durability of the technology products?
Two monoclonal antibodies to the prion protein and their use in combination as detection reagents for prions have been patented. Both antibodies are commercially available. Only non-exclusive licenses have been offered, to insure the widest possible use of these reagents in diagnostics, industry, and research. The antibodies are in use internationally and collaborative programs to train personnel in Canada, Mexico, and China are in progress. The preclinical test for scrapie has been transferred to the National Veterinary Services Laboratory. APHIS has established a national testing network, through which veterinary and state diagnostic laboratories will apply the technology under contract with APHIS. CAEV cELISA will be licensed and commercially available in the U.S. in 6-12 months.


7.List your most important publications in the popular press and presentations to organizations and articles written about your work. (NOTE: List your peer reviewed publications below).
1. Scrapie: Prions in the Placenta of AAQQ and AAQR sheep. Invited presentation at American Sheep Industry Convention, Reno, NV, January 28, 2005.

2. Prion accumulation in the sheep placenta / Goat scrapie genotyping project. Invited presentation at USAHA Sheep and Goat Committee, United States Animal Health Association Annual Meeting, Greensboro, NC, October 24, 2005.

3. Sheep scrapie: maternal and fetal genetics. Invited presentation at Animal Prion Diseases and the Americas, Ames, IA, October 14-16, 2005.

4. Using host immunogenetics as a prediction tool for ovine progressive pneumonia virus clinical disease. Invited presentation at the American Sheep Industry Convention, Reno, NV, January 2005.

5. Natural Sheep Scrapie: What have we learned? Invited presentation to the Department of Chemistry and Biochemistry at the University of Denver, Denver, CO, November 2004.

6. Predicting ovine progressive pneumonia virus loads using MHC Class II DRB1 immunogenetics. Invited presentation at the United States Animal Health Association Sheep and Goat Committee, Greensboro, NC, October 2004.

7. Lack of Natural Ovine Progressive Pneumonia Virus Transmission from OPPV-Infected Ewes to Their Lambs. Presentation at the Keystone Symposia HIV Pathogenesis, Banff, Canada, April 2005.


Review Publications
Alverson, J. 2005. Data sheet for scrapie. Animal Health and Production Compendium. Available: http://www.cabicompendium.org/ahpc/home.asp

Alexander, B.M., Stobart, R.H., Russell, W.C., Orourke, K.I., Lewis, G.S., Logan, J.R., Duncan, J.R., Moss, G.E. 2005. The incidence of genotypes at codon 171 of the prion protein gene (prnp) in five breeds of sheep and production traits of ewes associated with those genotypes. Journal of Animal Science. 83(2):455-459.


Herrmann, L.M., Mcguire, T.C., Hotzel, I., Lewis, G.S., Knowles Jr, D.P. 2005. Surface envelope glycoprotein is b-lymphocyte immunodominant in sheep naturally infected with ovine progressive pneumonia virus. Clinical and Diagnostic Laboratory Immunology. 12(6):797-800.


Herrmann, L.M. 2005. Needles: To Re-use or Not to Re-use?. Sheep Industry News. 9(5):2.


Johnson, M.L., Evoniuk, J.M., Stoltenow, C.L., Orourke, K.I., Redmer, D.A. 2005. Development of an assay to determine single nucleotide polymorphisms (snp) in the prion gene for the diagnosis of genetic susceptibility to scrapie in sheep. American Society of Animal Science. 56:151.


Evoniuk, J.M., Stoltenow, C.L., O'Rourke, K.I., Moore, B.L., Redmer, D.A. 2005. Assessment of the genetic risk and impact of lateral transmission in a valine-associated scrapie outbreak in sheep. American Journal of Veterinary Research. 66(:1-6.


http://www.ars.usda.gov/research/projects/projects.htm?ACCN_NO=405202&fy=2005

J Am Vet Med Assoc. 1992 Jan 15;200(2):164-7.
Recommendations of the International Roundtable Workshop on Bovine Spongiform Encephalopathy.
Gibbs CJ Jr,
Bolis CL,
Asher DM,
Bradley R,
Fite RW,
Johnson RT,
Mahy BW,
McKhann GM.
National Institutes of Health, Bethesda, MD 20892.

Recommendations of the working party were summarized as follows: Determine the status in all countries of their national cattle herds with respect to BSE. Attempt to develop a test to recognize BSE-infected animals before they become clinically ill. Establish procedures to prevent spread of BSE agent into the cattle populations, especially by eliminating feeds containing rendered ruminant proteins. Review the rendering processes, identify the sources and destinations of rendered products, and suggest appropriate changes if needed. Especially needed are standardized rendering procedures in regard to use of organic solvents, temperature, and duration of heat treatment. Review import and export regulations to reduce the risk of spreading BSE and to maximize opportunities for safe trading in cattle and cattle products. The scrapie-free certification program of the USDA was supported, and similar programs might be considered by other countries. If BSE/scrapie is diagnosed in a given country, determine baseline incidence of CJD in those countries and consider contributing to an international registry. The WHO should address the problems of BSE, formulate policy, participate in and coordinate research, and provide training opportunities for veterinary and human health care workers from eastern European countries and developing nations. Government and private agencies should consider increasing support for research on transmissibility and pathogenesis of CJD, BSE, CWD, scrapie, and transmissible mink encephalopathy. Prepare and publish a critical neuropathologic review of all spongiform encephalopathies, naturally and experimentally transmitted, defining the characteristics of each disease in the various species known to be susceptible. Consider producing guidelines for the biological and pharmaceutical industries with regard to sourcing, collecting, and processing bovine and ovine materials.

===================END================

Published online before print October 20, 2005

Proc. Natl. Acad. Sci. USA, 10.1073/pnas.0502296102
Medical Sciences

A newly identified type of scrapie agent can naturally infect sheep with resistant PrP genotypes

( sheep prion | transgenic mice )

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 *
*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, and approved September 12, 2005 (received for review March 21, 2005)

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.

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

Author contributions: H.L. designed research; A.L.D., V.B., O.A., F.R., T.L.L., J.-L.V., and H.L. performed research; T.B., B.B., P.S., and S.L.B. contributed new reagents/analytic tools; V.B., O.A., and H.L. analyzed data; and H.L. wrote the paper.

A.L.D. and V.B. contributed equally to this work.

To whom correspondence should be addressed.

Hubert Laude, E-mail: laude@jouy.inra.fr

www.pnas.org/cgi/doi/10.1073/pnas.0502296102


http://www.pnas.org/cgi/content/abstract/0502296102v1


Like lambs to the slaughter
31 March 2001
Debora MacKenzie
Magazine issue 2284
What if you can catch old-fashioned CJD by eating meat from a sheep infected with scrapie?
FOUR years ago, Terry Singeltary watched his mother die horribly from a degenerative brain disease. Doctors told him it was Alzheimer's, but Singeltary was suspicious. The diagnosis didn't fit her violent symptoms, and he demanded an autopsy. It showed she had died of sporadic Creutzfeldt-Jakob disease.

Most doctors believe that sCJD is caused by a prion protein deforming by chance into a killer. But Singeltary thinks otherwise. He is one of a number of campaigners who say that some sCJD, like the variant CJD related to BSE, is caused by eating meat from infected animals. Their suspicions have focused on sheep carrying scrapie, a BSE-like disease that is widespread in flocks across Europe and North America.

Now scientists in France have stumbled across new evidence that adds weight to the campaigners' fears. To their complete surprise, the researchers found that one strain of scrapie causes the same brain damage in ...

http://www.newscientist.com/article/mg16922840.300-like-lambs-to-the-slaughter.html

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

THE findings from Corinne Ida Lasmézas*, [dagger] , Jean-Guy Fournier*,
Virginie Nouvel*,

Hermann Boe*, Domíníque Marcé*, François Lamoury*, Nicolas Kopp [Dagger

] , Jean-Jacques Hauw§, James Ironside¶, Moira Bruce [||] , Dominique

Dormont*, and Jean-Philippe Deslys* et al, that The agent responsible
for French iatrogenic growth hormone-linked CJD taken as a control is
very different from vCJD but is similar to that found in one case of
sporadic CJD and one sheep scrapie isolate;

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

SEE HOW MANY POTENTIALLY BSE INFECTED SHEEP OR GOATS YOUR COUNTRY IMPORTED FROM UK ;

0208h023: UK exports of sheep, goats and sheep/goat meats and meat products (1988 - 2001)


http://www.vegsource.com/articles/sheep_exports.htm


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

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


[Docket No. 03-025IFA] FSIS Prohibition of the Use of Specified Risk Materials for Human Food and Requirement for the Disposition of Non-Ambulatory Disabled Cattle

03-025IFA
03-025IFA-2


http://www.fsis.usda.gov/OPPDE/Comments/03-025IFA/03-025IFA-2.pdf


THE SEVEN SCIENTIST REPORT ***


http://www.fda.gov/ohrms/dockets/dockets/02n0273/02n-0273-EC244-Attach-1.pdf

GOTTA LOVE THAT BSE MRR POLICY ADOPTED BY THE OIE VIA GW ET AL AT USDA !


SHUT UP AND SING !

GOD LOVES THE DIXIE CHICKS AND SO DO WE !


http://www.shutupandsingmovie.com/


once there, click on chicks 'play the trailer' above shut up & sing

coming this fall...........can't wait !!!

GOD BLESS FREE SPEECH, it still lives for now!


TSS




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