Experimental oral transmission of CWD to red deer (Cervus elaphus elaphus): early detection and late stage distribution of protease-resistant protein
Authors
Balachandran, A - CANADIAN FOOD INSPCTN AG Harrington, Noel - CANADIAN FOOD INSPCTN AG Algire, James - CANADIAN FOOD INSPCTN AG Souyrine, Andre - CANADIAN FOOD INSPCTN AG Orourke, Katherine Spraker, Terry - COLORADO ST UNIV
Submitted to: Canadian Journal of Veterinary Research Publication Type: Peer Reviewed Journal Publication Acceptance Date: December 1, 2008 Publication Date: N/A
Interpretive Summary: Farmed cervids may be exposed to the prion disorder chronic wasting disease through contact with free ranging or farmed infected Rocky Mountain elk, white tailed deer, mule deer, or moose. This is the first report of experimental transmission of chronic wasting disease to red deer, an economically important agricultural commodity in parts of North America. Brain tissue from infected Rocky Mountain elk was administered by the oral route of red deer. Deer were examined at 18 months after infection for evidence of abnormal prion protein, the marker for the disease. The abnormal protein was found throughout the brain, spinal cord and lymphoid tissues, with variable distribution in other organ systems. This finding confirms the potential susceptibility of this species to disease under natural conditions and the reliability of the current testing format for identifying the abnormal protein in the tissues routinely collected in surveillance programs. The widespread distribution of the abnormal protein in red deer indicates the potential for shedding of the agent into the environment. Technical Abstract: Chronic wasting disease CWD is the transmissible spongiform encephalopathy or prion disease of wild and farmed cervid ruminants, including Rocky Mountain elk (Cervus elaphus nelsoni), white tailed deer (Odocoileus virginianus), mule deer (Odocoileus hemionus), or moose (Alces alces). Reliable data on the susceptibility of other farmed cervid species, the distribution of the abnormal prion protein marker in brain and lymphoid tissues collected in surveillance programs, and the role of prion genotype are necessary for design of control programs for CWD in farmed cervids. In this study, red deer (Cervus elaphus elaphus) were exposed to the prion agent by oral administration of brain homogenates from infected Rocky Mountain elk. Antemortem testing was performed at 7 months post infection and the deer were euthanized when clinical disease was observed at approximately 18 months after infection. The abnormal prion protein was assayed by immunohistochemistry, enzyme linked immunosorbent assay and western blot. Abnormal prion protein was found in the spinal cord, brainstem, cerebellum, midbrain, thalamus, and cerebrum in all 4 infected red deer. Most of the lymph nodes throughout the body were positive for abnormal prion proteins. Abnromal prion protein was observed in some additional peripheral tissues in some but not all of the deer. In particular, most areas of the gastrointestinal tract were positive for abnormal prions, although the salivary glands were rarely positive. This study demonstrates the potential for oral transmission of chronic wasting disease to red deer and confirms the usefulness of the current testing methods for post mortem diagnosis of the disease in this species.
Project Team
Orourke, Katherine Knowles, Donald - Don White, Stephen Schneider, David Harrington, Robert - Bob
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Development of Sensitive in Vitro Techniques for Prion Detection Transgenic Analysis of Chronic Wasting Disease Strains Strain Typing of Chronic Wasting Disease (Cwd) and Scrapie by Intracerebral Inoculation into Transgenic and Inbred Mouse Lines Dissemination of Abnormal Prion Protein in the Neural and Extraneural Tissues of Wild Rocky Mountain Elk
http://www.ars.usda.gov/research/publications/publications.htm?SEQ_NO_115=228787
Oral transmission and early lymphoid tropism of chronic wasting disease PrPres in mule deer fawns (Odocoileus hemionus ) Christina J. Sigurdson1, Elizabeth S. Williams2, Michael W. Miller3, Terry R. Spraker1,4, Katherine I. O'Rourke5 and Edward A. Hoover1
Mule deer fawns (Odocoileus hemionus) were inoculated orally with a brain homogenate prepared from mule deer with naturally occurring chronic wasting disease (CWD), a prion-induced transmissible spongiform encephalopathy. Fawns were necropsied and examined for PrP res, the abnormal prion protein isoform, at 10, 42, 53, 77, 78 and 80 days post-inoculation (p.i.) using an immunohistochemistry assay modified to enhance sensitivity. PrPres was detected in alimentary-tract-associated lymphoid tissues (one or more of the following: retropharyngeal lymph node, tonsil, Peyer's patch and ileocaecal lymph node) as early as 42 days p.i. and in all fawns examined thereafter (53 to 80 days p.i.). No PrPres staining was detected in lymphoid tissue of three control fawns receiving a control brain inoculum, nor was PrPres detectable in neural tissue of any fawn. PrPres-specific staining was markedly enhanced by sequential tissue treatment with formic acid, proteinase K and hydrated autoclaving prior to immunohistochemical staining with monoclonal antibody F89/160.1.5. These results indicate that CWD PrP res can be detected in lymphoid tissues draining the alimentary tract within a few weeks after oral exposure to infectious prions and may reflect the initial pathway of CWD infection in deer. The rapid infection of deer fawns following exposure by the most plausible natural route is consistent with the efficient horizontal transmission of CWD in nature and enables accelerated studies of transmission and pathogenesis in the native species.
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These results indicate that mule deer fawns develop detectable PrP res after oral exposure to an inoculum containing CWD prions. In the earliest post-exposure period, CWD PrPres was traced to the lymphoid tissues draining the oral and intestinal mucosa (i.e. the retropharyngeal lymph nodes, tonsil, ileal Peyer's patches and ileocaecal lymph nodes), which probably received the highest initial exposure to the inoculum. Hadlow et al. (1982) demonstrated scrapie agent in the tonsil, retropharyngeal and mesenteric lymph nodes, ileum and spleen in a 10-month-old naturally infected lamb by mouse bioassay. Eight of nine sheep had infectivity in the retropharyngeal lymph node. He concluded that the tissue distribution suggested primary infection via the gastrointestinal tract. The tissue distribution of PrPres in the early stages of infection in the fawns is strikingly similar to that seen in naturally infected sheep with scrapie. These findings support oral exposure as a natural route of CWD infection in deer and support oral inoculation as a reasonable exposure route for experimental studies of CWD.
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http://vir.sgmjournals.org/cgi/content/full/80/10/2757
Subject: MAD DEER/ELK DISEASE AND POTENTIAL SOURCES Date: Sat, 25 May 2002 18:41:46 -0700 From: "Terry S. Singeltary Sr." Reply-To: BSE-L To: BSE-L
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INGREDIENTS
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DEPARTMENT OF HEALTH & HUMAN SERVICES PUBLIC HEALTH SERVICE FOOD AND DRUG ADMINISTRATION
April 9, 2001 WARNING LETTER
01-PHI-12 CERTIFIED MAIL RETURN RECEIPT REQUESTED
Brian J. Raymond, Owner Sandy Lake Mills 26 Mill Street P.O. Box 117 Sandy Lake, PA 16145 PHILADELPHIA DISTRICT
Tel: 215-597-4390
Dear Mr. Raymond:
Food and Drug Administration Investigator Gregory E. Beichner conducted an inspection of your animal feed manufacturing operation, located in Sandy Lake, Pennsylvania, on March 23, 2001, and determined that your firm manufactures animal feeds including feeds containing prohibited materials. The inspection found significant deviations from the requirements set forth in Title 21, code of Federal Regulations, part 589.2000 - Animal Proteins Prohibited in Ruminant Feed. The regulation is intended to prevent the establishment and amplification of Bovine Spongiform Encephalopathy (BSE) . Such deviations cause products being manufactured at this facility to be misbranded within the meaning of Section 403(f), of the Federal Food, Drug, and Cosmetic Act (the Act).
Our investigation found failure to label your swine feed with the required cautionary statement "Do Not Feed to cattle or other Ruminants" The FDA suggests that the statement be distinguished by different type-size or color or other means of highlighting the statement so that it is easily noticed by a purchaser.
In addition, we note that you are using approximately 140 pounds of cracked corn to flush your mixer used in the manufacture of animal feeds containing prohibited material. This flushed material is fed to wild game including deer, a ruminant animal. Feed material which may potentially contain prohibited material should not be fed to ruminant animals which may become part of the food chain.
The above is not intended to be an all-inclusive list of deviations from the regulations. As a manufacturer of materials intended for animal feed use, you are responsible for assuring that your overall operation and the products you manufacture and distribute are in compliance with the law. We have enclosed a copy of FDA's Small Entity Compliance Guide to assist you with complying with the regulation... blah, blah, blah...
http://www.fda.gov/foi/warning_letters/g1115d.pdf
above urls dead, go here ;
http://madcowfeed.blogspot.com/2008/07/docket-03d-0186-fda-issues-draft.html
Friday, September 4, 2009
FOIA REQUEST ON FEED RECALL PRODUCT 429,128 lbs. feed for ruminant animals may have been contaminated with prohibited material Recall # V-258-2009
http://madcowfeed.blogspot.com/2009/09/foia-request-on-feed-recall-product.html
Saturday, August 29, 2009
FOIA REQUEST FEED RECALL 2009 Product may have contained prohibited materials Bulk Whole Barley, Recall # V-256-2009
http://madcowfeed.blogspot.com/2009/08/foia-request-feed-recall-2009-product.html
nation and world
Deer mystery solved Experts say a fatal brain disease is passed in feces before illness appears. By Sandra Blakeslee The New York Times Posted: 09/10/2009 01:00:00 AM MDT
Researchers are reporting that they have solved a long- standing mystery about the rapid spread of a fatal brain infection in deer, elk and moose in the Midwest and West.
The infectious agent, which leads to chronic wasting disease, is spread in the feces of infected animals long before they become ill, according to a study published online Wednesday by the journal Nature. The agent is retained in the soil, where it, along with plants, is eaten by other animals, which become infected.
The finding explains the extremely high rates of transmission among deer, said the study's lead author, Dr. Stanley B. Prusiner, director of the Institute for Neurodegenerative Diseases at the University of California, San Francisco.
First identified in deer in Colorado in 1967, the disease is found throughout 14 states and two Canadian provinces. It leads to emaciation, staggering and death.
Unlike other animals, Prusiner said, deer give off the infectious agent, a form of protein called a prion, from lymph tissue in their intestinal linings up to a year before they develop the disease. By contrast, cattle that develop the related mad cow disease do not easily shed prions into the environment but accumulate them in their brains and spinal tissues.
There is no evidence to date that humans who hunt, kill and eat deer have developed chronic wasting disease. Nor does the prion that causes it pass naturally to other animal species.
The prion diseases include Creutzfeldt-Jakob, which leads to dementia and death in humans. Each prion disease is caused by a different strain, and all strains behave somewhat differently.
In the case of chronic wasting disease, "it turns out prions exploit the oldest trick in the book used by pathogens and parasites," said Dr. Mike Miller, a veterinarian at the Colorado Division of Wildlife who is an expert on chronic wasting disease. "Fecal-oral transmission is very effective."
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http://www.denverpost.com/headlines/ci_13302683
> Deer mystery solved
i doubt this problem is solved yet. maybe one part of the puzzle, but these cervids have also been fed high protein feed for years. and the oral route is highly sufficient. and what about cwd passing from mother to baby ??? these questions have not been answered yet, and to claim ''DEER MYSTERY SOLVED'', is by far from the truth, yet, in my opinion. ...
Monday, January 05, 2009
CWD, GAME FARMS, BAITING, AND POLITICS
http://chronic-wasting-disease.blogspot.com/2009/01/cwd-game-farms-baiting-and-politics.html
nation and world
Deer mystery solved
Experts say a fatal brain disease is passed in feces before illness appears.
By Sandra BlakesleeThe New York Times
http://www.denverpost.com/headlines/ci_13302683
> Deer mystery solved
i doubt this problem is solved yet. maybe one part of the puzzle, but these cervids have also been fed high protein feed for years. and the oral route is highly sufficient. and what about cwd passing from mother to baby ??? these questions have not been answered yet, and to claim ''DEER MYSTERY SOLVED'', is by far from the truth, yet, in my opinion. ...Title: Experimental oral transmission of chronic wasting disease (CWD) to red deer (Cervus elaphus elaphus): early detection and late stage distribution of protease-resistant protein (PrP-res)
snip... see TSS full comments here ;
http://www.denverpost.com/headlines/ci_13302683
Asymptomatic deer excrete infectious prions in faeces Gültekin Tamgüney1,2, Michael W. Miller3, Lisa L. Wolfe3, Tracey M. Sirochman3, David V. Glidden4, Christina Palmer1, Azucena Lemus5, Stephen J. DeArmond1,5 & Stanley B. Prusiner1,21.Institute for Neurodegenerative Diseases, 2.Department of Neurology, University of California, San Francisco, California, 94143 USA 3.Colorado Division of Wildlife, Wildlife Research Center, Fort Collins, Colorado, 80526 USA 4.Department of Epidemiology and Biostatistics, 5.Department of Pathology, University of California, San Francisco, California, 94143 USA Correspondence to: Stanley B. Prusiner1,2 Correspondence and requests for materials should be addressed to S.B.P. (E-mail: Email: mhtml:%7B33B38F65-8D2E-434D-8F9B-8BDCD77D3066%7Dmid://00000130/!x-usc:mailto:stanley@ind.ucsf.edu.)Top of pageAbstractInfectious prion diseases1-scrapie of sheep2 and chronic wasting disease (CWD) of several species in the deer family3, 4-are transmitted naturally within affected host populations. Although several possible sources of contagion have been identified in excretions and secretions from symptomatic animals5, 6, 7, 8, the biological importance of these sources in sustaining epidemics remains unclear. Here we show that asymptomatic CWD-infected mule deer (Odocoileus hemionus) excrete CWD prions in their faeces long before they develop clinical signs of prion disease. Intracerebral inoculation of irradiated deer faeces into transgenic mice overexpressing cervid prion protein (PrP) revealed infectivity in 14 of 15 faecal samples collected from five deer at 7-11 months before the onset of neurological disease. Although prion concentrations in deer faeces were considerably lower than in brain tissue from the same deer collected at the end of the disease, the estimated total infectious dose excreted in faeces by an infected deer over the disease course may approximate the total contained in a brain. Prolonged faecal prion excretion by infected deer provides a plausible natural mechanism that might explain the high incidence and efficient horizontal transmission of CWD within deer herds3, 4, 9, as well as prion transmission among other susceptible cervids.
http://www.nature.com/nature/journal/vaop/ncurrent/full/nature08289.html
Wednesday, June 11, 2008
Transmission and Detection of Prions in Feces
The Journal of Infectious Diseases 2008;198:81-89 © 2008 by the Infectious Diseases Society of America. All rights reserved. 0022-1899/2008/19801-0015$15.00 DOI: 10.1086/588193
http://chronic-wasting-disease.blogspot.com/2008/06/transmission-and-detection-of-prions-in.html
http://chronic-wasting-disease.blogspot.com/2009/09/asymptomatic-deer-excrete-infectious.html
Terry S. Singeltary Sr.
Labels: animal protein, CJD, CWD, FECES, feed, high infection rate, oral route, URINE