PROCEEDINGS ONE HUNDRED AND Nineteenth ANNUAL MEETING of the USAHA BSE, CWD, SCRAPIE, PORCINE TSE PRION October 22 28, 2015

PROCEEDINGS ONE HUNDRED AND Nineteenth ANNUAL MEETING of the UNITED STATES ANIMAL HEALTH ASSOCIATION Rhode Island Convention Center Providence, Rhode Island October 22 28, 2015

 

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II. C. USAHA JOINT SCIENTIFIC SESSION ABSTRACTS AND POSTERS

 

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MANAGING CWD IN FARMED CERVIDS

 

Nicholas J. Haley

 

Diagnostic Medicine and Pathobiology, Kansas State University, Manhattan, KS

 

Chronic wasting disease (CWD) is an efficiently transmitted spongiform encephalopathy of cervids (e.g. deer, elk, and moose), and is the only known prion disease affecting both free-ranging wildlife and captive animals. The management of CWD in farmed cervids will require three avenues of research: 1) the development of a sensitive live animal test, 2) the discovery and implementation of a safe and effective vaccine strategy, and 3) with or without a vaccine, the identification and cultivation of CWD-resistant cervids. The antemortem detection of CWD and other prion diseases has proven difficult, due in part to difficulties in identifying an appropriate peripheral tissue specimen and complications with conventional test sensitivity. At present, biopsies of the recto-anal mucosalassociated lymphoid tissues (RAMALT) have shown promising sensitivity in various assays and are not impractical to collect in live animals. Nasal brush collections have likewise proven both sensitive and practical for identification of prion infections in humans, though in cervids both rectal biopsy and nasal brush collection sensitivity is critically dependent on stage of infection and genetic background. A blood test would be ideal; however rudimentary assays currently in development have yet to be evaluated blindly on naturally occurring populations or on a large scale. Vaccine development is currently underway at several institutions, though an effectively protective strategy has yet to be identified. Ultimately, genetic resistance to CWD may be a critical corner piece in the management of CWD in farmed cervids – an approach which has been used effectively to reduce the incidence of scrapie in sheep worldwide. By exploiting resistant PrP alleles in currently available white-tail and elk genetic pools, and searching various isolated populations for evidence of additional resistance mechanisms, a suitable approach to improving CWD resistance in farmed cervids may be identified. Our research has specifically sought to develop an antemortem test for CWD using amplification-based assays on collections from recent CWD depopulations, while additionally using these assays to model CWD resistance in cervid populations. Our findings from this research represent the early stages in the management and ultimately eradication of CWD in farmed deer and elk.

 

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REPORT OF THE COMMITTEE ON CAPTIVE WILDLIFE AND

 

ALTERNATIVE LIVESTOCK

 

Chair: Peregrine Wolff, NV

 

Vice Chair: Julie Napier, NE

 

Thomas Albert, VA; Paul Anderson, MN; James Averill, MI; Kay Backues, OK; Bill Barton, ID; Scott Bender, AZ; Warren Bluntzer, TX; Tom Bragg, NE; Rhonda Brakke, IA; Deborah Brennan, MS; Sarah Cannizzo, OR; Beth Carlson, ND; Susan Culp, TX; Donald Davis, TX; Barbara Determan, IA; Mark Drew, ID; John Fischer, GA; Nancy Frank, MI; Richard French, NH; Tam Garland, TX; Robert Gerlach, AK; Paul Gibbs, FL; Colin Gillin, OR; Michael Gilsdorf, MD; Chester Gipson, MD; Paul Grosdidier, KS; Keith Haffer, SD; Greg Hawkins, TX; Bill Hawks, DC; Kristi Henderson, IL; Terry Hensley, TX; Michael Herrin, OK; Linda Hickam, MO; Robert Hilsenroth, FL; David Hunter, MT; John Huntley, WA; Russell Iselt, TX; Donald Janssen, CA; Diane Kitchen, FL; Patrice Klein, MD; Todd Landt, IA; John Lawrence, ME; Charles Lewis, IA; Travis Lowe, MN; Mark Luedtke, MN; Bret Marsh, IN; David Marshall, NC; Chuck Massengill, MO; Robert Meyer, CO; Eric Mohlman, NE; Yvonne Nadler, IL; Jeffrey Nelson, IA; Sandra Norman, IN; Dustin Oedekoven, SD; Mitchell Palmer, IA; Janet Payeur, IA; William Pittenger, MO; Jewell Plumley, WV; Justin Roach, OK; Jonathan Roberts, LA; Keith Roehr, CO; Susan Rollo, TX; Shawn Schafer, OH; David Schmitt, IA; Dennis Schmitt, MO; Marc Schwabenlander, MN; Andy Schwartz, TX; Charly Seale, TX; Laurie Seale, WI; Daryl Simon, MN; Jonathan Sleeman, WI; David Smith, NY; Diane Stacy, LA; Kelly Straka, MO; Manoel Tamassia, NJ; Robert Temple, OH; Lee Ann Thomas, MD; Brad Thurston, IN; Jeff Turner, TX; Kathleen Turner, FL; Rick Wahlert, CO; Curt Waldvogel, OH; Ray Waters, IA; Steve Weber, CO; Skip West, OK; Ellen Wiedner, FL; Margaret Wild, CO; Kyle Wilson, TN; Nora Wineland, MO; Richard Winters, Jr., TX; Mary Wood, WY; Glen Zebarth, MN.

 

The Committee met on October 27, 2015, at the Rhode Island Convention Center in Providence, Rhode Island from 8:00 a.m. to 12:35 p.m. There were 39 members and 40 guests present. The one previous resolution from 2014 was addressed in the Annual update for the Cervid Health Team, Fiscal year (FY) 2015.

 

Charly Seale presented the report of the Subcommittee on Farmed Cervidae. The full report is found at the end of this report.

 

Presentations

 

Evaluation of a Novel Recombinant Protein Fusion Vaccine for CWD in Elk – Preliminary Data

 

Mary Wood, Wyoming Game and Fish Department

 

Chronic wasting disease (CWD) is a fatal neurologic disease of cervids which threatens both free-ranging and captive populations. Currently there are minimal management options for limiting spread of CWD. We evaluated a novel recombinant protein fusion vaccine developed by Pan-Provincial Vaccine

 

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Enterprises (PREVENT), in elk. Thirty-eight female elk calves (Cervus elaphus) were captured on the South Park Feedground in Western Wyoming and transported to the Thorne-Williams Wildlife Research Center (TWRC). Calves were divided randomly into two groups, control (n=19) and vaccine (n=19). All elk were genotyped to determine Prnp codon 132 polymorphisms. Primary and booster vaccines were given intramuscularly six weeks apart approximately 2-3 weeks after arrival at the TWRC and yearly thereafter. Elk were challenged via natural environmental exposure to CWD at the facility. Elk were monitored daily for behavioral and physical signs of clinical CWD and were evaluated for CWD infection via rectal biopsy. All elk with clinical CWD were humanely euthanized and infection was confirmed via ELISA and immunohistochemistry. Both vaccinates and controls developed clinical CWD, with vaccinates showing a shorter survival time (p=0.014). This research is ongoing and further results are necessary before final conclusions are made.

 

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Rectal Biopsy as an Ante Mortem Assay for CWD: Diagnostic and Regulatory Considerations

 

Tracy Nichols, USDA Wildlife Services, National Wildlife Research Center

 

Summary:

 

 A considerable amount of research has been done in both deer and elk regarding rectal biopsy

 

 High quality rectal biopsies are needed to have reliable results

 

 Route and dose of CWD exposure likely influences disease incubation period

 

 Rectal biopsy has high specificity and moderate sensitivity that is dependent upon disease progression and genotype

 

 Disease progression and subsequent detection in the rectal mucosa is influenced by genetics at codon 96 in WTD and at codon 132 in elk

 

 CWD proliferates and trafficks faster in codon 96 GG WTD than in GS or SS animals, making detection by rectal biopsy less reliable in GS or SS deer

 

 Deer and elk with CWD prions present only in the retropharyngeal lymph nodes often do not have positive rectal biopsies

 

Annual Update for the Cervid Health Team, Fiscal Year (FY) 2015

 

Randy Pritchard, US Department of Agriculture, Animal and Plant Health Inspection Service, (APHIS) Veterinary Services (VS)

 

Voluntary Chronic Wasting Disease (CWD) Herd Certification Program The APHIS National CWD Herd Certification Program (HCP) was implemented in 2014. It is a voluntary Federal-State-industry cooperative program administered by APHIS and implemented by participating States. The program provides uniform national herd certification standards that minimize the risk of spreading CWD in farmed cervid populations. Participating States and herd owners must comply with requirements for animal identification, fencing, recordkeeping, inspections/inventories, as well as animal mortality testing and response to any CWD-exposed, suspect, and positive herds. APHIS monitors the Approved State HCPs to ensure consistency with Federal standards through annual reporting by the States. With each year of successful surveillance, participating herds will advance in status until reaching five years with no evidence of CWD, at which time herds are certified as being low-risk for CWD. Only captive cervids from enrolled herds certified as low risk for CWD may move interstate. Currently, 30 States participate in the voluntary CWD Herd Certification Program; 29 have Approved HCPs and one has Provisional Approved status. VS is working with the remaining State to transition it to Approved status. FY2015 marks the second year that Approved States have submitted their CWD HCP annual reports to APHIS. APHIS is currently reviewing these reports.

 

Review of CWD Program Standards

 

The CWD Program Standards provide clarification and guidance on how to meet CWD Herd Certification Program and interstate movement requirements.

 

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VS committed to an annual review of the Program Standards by representatives of the cervid industry and appropriate State and Federal agencies. VS planned to perform a review in FY2015; however, this did not occur due to the response to highly pathogenic avian influenza (HPAI). VS expects to conduct a review in FY2016.

 

CWD in Farmed and Wild Cervids

 

Retrospective Epidemiology of CWD in Farmed Cervids

 

In response to a 2014 USAHA Resolution, VS asked States to include a retrospective summary of the epidemiology of all positive herds with their annual HCP reports for FY2015. Unfortunately, the response to HPAI delayed completion of this summary. Five States reported information to date. A few States indicated that they did not have the resources to devote to this request. VS will continue to gather this data and to collect more comprehensive data in the future.

 

Summary of CWD detections

 

As of September 30, 2015, CWD has been confirmed in wild deer and elk in 21 US States, and in farmed cervids in 16 States. In total, 23 States have identified CWD in wild and/or farmed cervids. CWD has been reported in 70 farmed cervid herds in the United States. Confirmation of the disease in three free-ranging, wild white-tailed deer in Michigan in 2015 marked the first report of CWD in the wild cervid population in this State.

 

FY2015 CWD Detections in Farmed Cervids

 

In FY2015, CWD was identified in eight farmed cervid herds: one whitetailed deer breeding herd in Pennsylvania, one elk breeding herd in Utah (traced back from a hunting facility in Utah), one white-tailed deer (WTD) breeding herd and one WTD hunting preserve in Ohio (owned by the same producer), two WTD breeding herds in Wisconsin, one WTD and elk herd in Texas, and a second WTD herd in Texas (traced from the first positive herd in Texas). The positive animals in Utah, Ohio, and Texas represented the first reported cases of CWD in captive cervids in all three of these States. White-Tailed Deer Breeding Herd, Pennsylvania

 

On October 6, 2014, the National Veterinary Services Laboratories (NVSL) confirmed CWD in a 6-year-old doe from a captive WTD breeding facility in Reynoldsville, Pennsylvania. The doe was euthanized and tested because she was classified as a CWD-exposed animal that had previously resided in two trace back exposed herds. This herd was assembled in 2013 through the purchase of 16 animals from other HCP-certified herds in Pennsylvania, and had been under quarantine for receiving exposed animals from a trace back exposed herd. The remaining herd of eight WTD was depopulated with Federal indemnity on February 18, 2015, and no additional positive animals were detected. USDA collected samples for research purposes.

 

Elk Breeding Herd, Utah

 

On December 23, 2014, NVSL confirmed CWD in 3-year-old captive elk. The elk had been at a hunting park located in northern Utah, where he had resided for approximately 3 weeks prior to being hunter killed. All hunter-killed animals at the hunt park are required to be tested for CWD, and this animal

 

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was sampled through routine surveillance. The elk was traced back to its herd of origin, and that facility was quarantined. The herd was assembled in 1999 with bulls, and later elk cows, that originated from Colorado. Historical testing records for the herd were unavailable. The remaining 70 elk were depopulated using Federal indemnity funds on March 3, 2015, and an additional 25 elk were confirmed as CWD-positive. USDA collected samples for research purposes. White-Tailed Deer Hunting Preserve, Ohio

 

On October 22, 2014, NVSL confirmed CWD in a buck taken from a captive WTD deer hunting preserve in Ohio. This was the first time that CWD had been detected in Ohio. The preserve was tested as part of Ohio’s CWD monitoring program. The herd had been under quarantine since April 2014 because it was a trace-forward herd associated with a CWD-exposed herd in Pennsylvania. The positive animal was traced to its herd of origin, a captive WTD breeding herd in Pennsylvania, through DNA identity testing. On November 26, 2014, the Ohio State Veterinarian issued an Order of Destruction for animals on the hunting preserve. The State executed this Order on April 27-30, 2015. The herd of 224 WTD was depopulated and no other positives were detected. USDA did not provide Federal indemnity.

 

White-Tailed Deer Breeding Herd, Ohio

 

On March 31, 2015, NVSL confirmed CWD infection in a 5-year-old WTD doe from a captive breeding herd in Holmesville, Ohio. The index animal was received from a Wisconsin WTD farm in January 2013. The CWD-positive herd was owned by the same individual as the Ohio hunt preserve that was found to be CWD positive in October 2014. On May 22, 2015, NVSL confirmed a second positive case in the same herd - a yearling WTD doe that was a natural addition in the same breeding herd. The herd had been under quarantine since April 1, 2014 due to epidemiological linkages with two WTD herds in Pennsylvania – one a positive herd and the other a traceback exposed herd. USDA provided Federal indemnity and depopulated this herd on June 15 and 16, 2015. USDA collected samples for research purposes. NVSL confirmed CWD in 16 additional animals in the herd. Of the 16 positives, one was natural addition and the rest were purchased additions. The positive animals were purchased from February 26, 2013 through September 24, 2013, except for one purchased in 2012. Eleven purchased additions traced-back to three herds in Pennsylvania and four purchased additions traced to three other herds in Ohio.

 

White-Tailed Deer Breeding Herd, Wisconsin

 

On October 6, 2014, NVSL confirmed CWD in a 2-year-old doe born in June of 2012 that died on a Richland County farm. The facility is within the CWD management zone in Wisconsin. The remaining 51 deer were euthanized on November 20, 2014, and seven additional positives (all males born in 2012) were found. Two of these seven were purchased additions with the last added to the herd in January 2013. All sales from this herd were to shooting preserves. This premise was double fenced and had been compliant in a herd certification program for over ten years.

 

White-Tailed Deer Breeding Herd, Wisconsin

 

REPORT OF THE COMMITTEE

 

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On June 19, 2015, NVSL confirmed CWD in a seven-year-old female WTD from a breeding facility in Eau Claire County. The doe was a natural addition to this breeding herd. This is the first positive CWD case, captive or wild, in this county. The doe was found dead and was showing no clinical signs of CWD at the time of death. Since 2003, this herd has tested 391 animals for CWD and all had “not detected” results. In addition, 317 animals have tested “not detected” from the associated hunting preserve over the same time period. A second positive natural addition doe from this herd was confirmed positive by NVSL on September 10, 2015. Several escape episodes have occurred from this herd. The herd is currently under quarantine and plans are underway for depopulation with State indemnity.

 

White-Tailed Deer and Elk Breeding Herd, Texas

 

On June 30, 2015, NVSL confirmed CWD in a 2-year-old WTD buck from a captive WTD and elk breeding herd in Medina County, Texas, approximately 500 miles from previously reported positive free-ranging mule deer in far West Texas. This was the first time that the disease had been detected in farmed cervids in the State. The index buck was born on the premises and found dead on June 18, 2015. Over 40 high-risk deer (i.e., pen mates, dam, others) were euthanized and tested after the index case was found. The NVSL confirmed CWD infection in two of those deer. Interestingly, all three of the positive deer identified to date on this premises have the same AI sire. However, the significance of this finding is unclear. In the past five years, records indicate that 130 WTD from 33 facilities moved into the positive herd and 838 WTD moved out of the positive herd to 147 different herds. One positive WTD was found in one of these trace-out herds (see herd description below). Additionally, 23 elk were also moved from this herd to another herd in TX in 2014. All trace-outs have been intrastate except for movements to two premises in Mexico. Premises that have received deer from the index herd are under movement restrictions. VS is collaborating with animal health authorities in Mexico. VS paid indemnity and depopulated this herd on September 30, 2015, and no additional positive animals were detected. USDA collected samples for research purposes.

 

White-Tailed Deer Herd, Texas

 

On September 14, 2015 NVSL confirmed CWD from tissues from a WTD in Lavaca County, Texas. This animal was a traceout from the first CWD positive herd from June 30, 2015. Additional epidemiology is ongoing.

 

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Chronic Wasting Disease Risk Perception: Why Can’t We All Just Get Along?

 

Krysten Schuler, Animal Health Diagnostic Center, Cornell University, College of Veterinary Medicine

 

Additional authors: Alyssa Wetterau, Elizabeth M. Bunting, and Hussni Mohammed

 

Chronic wasting disease (CWD) is a disease of concern to agencies, sportsmen, and businesses dependent on cervid species. However, disease risk perceptions may vary considerably between groups on wildlife and agriculture sides. We administered an online survey using Qualtrics survey software to the state wildlife agency (n=20), state agriculture agency (n=20), federal (United States Geological Survey (USGS), USDA) and other state agencies (n=9), academics (n=5), sportsmen (n=45), and captive cervid farmers (n=13) between March 2013 and 2014 to gauge attitudes toward potential hazards for CWD transmission to wild white-tailed deer or captive cervids. Of 15 hazards, the high-ranking risks were CWD existing undetected in the wild >1 year, decreased testing without subsidies, high wild deer densities, fence line contact, intrastate movement and importation of captive deer. State wildlife and agriculture officials ranked risks higher than other groups, with captive cervid farmers 50% below the average. Of six identified

 

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hazard pathways, importation of live cervids and escaped cervids was the highest risk for the wildlife agency (72% probability of CWD introduction), other agency and academic professionals (45%), and sportsmen (43%,) while the agriculture agency was most concerned by wild deer migration with high deer densities (46%). Captive cervid operators were threatened by importation of wild deer parts and then infected carcasses or parts left on the landscape (29%). Professional groups ranked generalized risks similarly, particularly for wild deer, but varied on the most likely disease pathway scenario. These regulating agencies also ranked risks higher than those in the captive cervid industry. Recommendations from this study include reaching agreement that CWD is a problem and strive for prevention and containment. Adequate funding by state and federal agencies for wildlife health programs and stakeholder education, as well as improved wild deer surveillance, would decrease CWD risks. The captive cervid industry could investigate selfregulation or insurance options, in addition to the USDA program. This information could be used to further investigate risk management and communication strategies.

 

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REPORT OF THE COMMITTEE

 

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Modeling CWD Resistance in Vitro

 

Nicholas Haley, Department of Microbiology and Immunology, Midwestern University

 

A review of the current science involving in vitro amplification assays which can help predict transmissible spongiform encephalopathies (TSE) resistance and how this modeling strategy may be utilized to manage CWD through host resistance.

 

Committee Business:

 

The Committee received, discussed and voted on the following five resolutions. The first four were approved and forwarded to the Committee on Resolutions. The fifth did not pass.

 

1. Live Animal Testing for Chronic Wasting Disease

 

2. Chronic Wasting Disease Program Standards - Guidance on Responding to CWD Positive Herds

 

3. Chronic Wasting Disease Testing Protocol for Wild Cervidae

 

4. Tuberculosis Testing Protocol for Farmed cervidae

 

5. External Review of APHIS-VS CWD Program (not approved).

 

There was not further business, and the meeting was adjourned.

 

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REPORT OF THE SUBCOMMITTEE ON FARMED CERVIDAE

 

Co-chairs: Charly Seale, Exotic Wildlife Association Brett Marsh, Indiana Board of Animal Health Paul Anderson, Minnesota Board of Animal Health The Subcommittee on Farmed Cervidae met on October 26, 2015 at the Rhode Island Convention Center in Providence, Rhode Island. The following committee members were present: Shawn Schafer, ND; Eric Mohlman, NE; John Fischer, GA; David Hunter, MT; Collin Gillin, OR; and Glen Zebarth, MN. Warren Bluntzer, TX and Robert Meyer, WY were not able to attend. There were a total of 80 people in attendance at the meeting.

 

Reports

 

Dr. Tracy Nichols, USDA-Animal Plant Health Inspection Service (APHIS), Wildlife Services (WS), National Wildlife Research Center (NWRC) presented new information on Ante Mortem Testing for Chronic Wasting Disease (CWD).

 

Dr. Nathan Shotts, Veterinary Reproduction and Genetics PLLC and Tom Van Kleef, VERGE, presented on the Verge surgical procedure for Ante Mortem CWD-Testing-Options and Implementation.

 

Dr. Walt Cook, Texas A&M University, presented the results of his research on drug residues in white tailed deer.

 

Dr. Alecia Naugle and Dr. Randy Pritchard, USDA-APHIS-Veterinary Services (VS), presented on recent cases of CWD in the United States, issues surrounding the CWD Program Standards, protocols for dealing with CWD positive herds including trace forward and trace back, current status of developing an approved live test for CWD, and issues surrounding the use of the Dual Path Platform (DPP) tuberculosis test in cervidae.

 

Four resolutions were drafted, discussed, voted upon and passed out of the Subcommittee on Farmed Cervidae for subsequent consideration and possible action by the full USAHA Committee on Captive Wildlife and Alternative Livestock. These resolutions are as follows:

 

1. Live Animal Testing for Chronic Wasting Disease

 

2. Chronic Wasting Disease Program Standards - Guidance on Responding to CWD positive Herds

 

3. Chronic Wasting Disease Testing Protocol for Wild Cervidae

 

4. Tuberculosis testing protocol for farmed cervidae

 

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287 potent and efficacious for animals is imperative for quality patient care. This includes ketamine, which is used for animal immobilization, sedation and pain management. In some areas, ketamine is the only analgesic/anesthetic agent available to the veterinary profession and additional restrictions on its use would have a significant negative impact on animal health and welfare on a global scale.

 

RESOLUTION:

 

The United States Animal Health Association (USAHA) opposes international and domestic regulatory action, specifically changes in scheduling, that would result in ketamine becoming more difficult, if not impossible, to obtain within the United States by licensed veterinarians for the authorized treatment of animals. The USAHA also requests that the Food and Drug Administration consider this resolution as they develop their comments to the World Health Organization Expert Committee.

 

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RESOLUTION NUMBER: 9 APPROVED

 

SOURCE: COMMITTEE ON CAPTIVE WILDLIFE AND ALTERNATIVE LIVESTOCK

 

SUBJECT MATTER: CHRONIC WASTING DISEASE PROGRAM STANDARDS - GUIDANCE ON RESPONDING TO CHRONIC WASTING DISEASE POSITIVE HERDS

 

BACKGROUND INFORMATION:

 

There is a need to review, revise and update the protocols for how the cervidae industry and state and federal agencies respond to chronic wasting disease (CWD) positive herds, trace back herds and trace forward herds. There is also a need to update and revise the protocols for how to release movement restrictions and reinstate herds to the appropriate herd certification program status. In order to (1) complete CWD investigations more quickly, (2) avoid unnecessary depopulation of farmed cervidae herds, and (3) avoid unnecessarily long quarantine periods, these protocols must include the use of live animal tests for CWD such as the rectal biopsy (rectoanal mucosa-associated lymphoid tissue (RAMALT)).

 

RESOLUTION:

 

The United States Animal Health Association urges the United States Department of Agriculture, Animal and Plant Health Inspection Service, Veterinary Services to amend the Chronic Wasting Disease (CWD) Program Standards by deleting all language in Part B, “Guidance on Responding to CWD Affected Herds” and rewrite Part B under the guidance of a working group of state and federal regulatory officials and representatives from the farmed cervidae industry.

 

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REPORT OF THE COMMITTEE

 

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RESOLUTION NUMBER: 10 APPROVED SOURCE: COMMITTEE ON CAPTIVE WILDLIFE AND ALTERNATIVE LIVESTOCK

 

SUBJECT MATTER: CHRONIC WASTING DISEASE TESTING PROTOCOL FOR WILD CERVIDAE

 

BACKGROUND INFORMATION:

 

Over the last 15 years the United States Department of Agriculture (USDA), Animal and Plant Health Inspection Service (APHIS), Veterinary Services (VS) and state regulatory officials have worked to prevent and control the spread of Chronic Wasting Disease (CWD).

 

Producers farming CWD susceptible species can only move their animals interstate if they are in compliance with the CWD program set forth in 9 Code of Federal Regulations (CFR) Parts 55 and 81 that states animals must originate from herds with five years of CWD monitored status. State Wildlife agencies that plan and execute elk restoration projects from one state to another are moving CWD susceptible species interstate without following minimum interstate movement requirements set for farmed cervidae. Instead, CFR 81.3 states the source population be considered “low risk” by the receiving state and USDA-APHIS.

 

To date, over two dozen herds of wild elk have been captured and transported to other states across the nation without following the Chronic Wasting Disease protocol set forth in the CWD program for farmed cervidae. The movement of CWD susceptible cervid species with unknown CWD status by state wildlife agencies can undermine the success of CWD control programs that have been in place in many states for more than a decade. CWD has been found in 23 states. Eight of the 23 states have detected CWD in the free-ranging deer populations but not in the farmed cervid herds.

 

RESOLUTION:

 

The United States Animal Health Association urges the United States Department of Agriculture, Animal and Plant Health Inspection Service, Veterinary Services to work with stakeholders to develop a guidance document on determining chronic wasting disease risk levels of source herds for interstate cervid restoration projects.

 

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RESOLUTION NUMBER: 11 APPROVED

 

SOURCE: COMMITTEE ON CAPTIVE WILDLIFE AND ALTERNATIVE LIVESTOCK

 

SUBJECT MATTER: Live Animal Testing For Chronic Wasting Disease BACKGROUND INFORMATION:

 

Detection of Chronic Wasting Disease (CWD) in live animals remains an important component of CWD Prevention and Control Programs. The United

 

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States Animal Health Association (USAHA) and the United States Department of Agriculture (USDA) recognize this and have stated such for several years (see USAHA resolutions 14 (2011), 16 (2011), 20 (2012), 13 and 23 combined (2012), 24 (2012), and 28 (2015), with associated USDA replies).

 

Notwithstanding the development and evaluation of the rectoanal mucosa-associated lymphoid tissue (RAMALT) test, CWD program regulatory analysis and actions continue to rely on post-mortem tissue collections, with Immunohistochemistry (IHC) testing in the laboratory, in accordance with current USDA CWD Program Standards.

 

This continues to impose significant adverse impacts on the industry, the economies of local communities, and the regulatory agencies involved. Postmortem testing also limits the data and information that can be gathered and used to improve management and control of CWD.

 

The need for a successful live test option, with the accuracy and sensitivity equal to current post-mortem testing, is critical. A rational deployment of such a solution will require regulatory updates and guidelines to account for live testing of white-tailed deer, in both a trace-forward / traceback scenario, as well as in CWD Herd Certification and/or Management Programs.

 

A group of veterinarians with specific white-tailed deer experience, led by VERGE PLLC, has successfully developed an ante-mortem procedure to collect the tissues required for IHC testing, as well as enzyme linked immunosorbent assay and other approved test protocols. This solution, the VERGE procedure, provides the same medial retropharyngeal lymph node (MRPLNs) tissues with negligible morbidity or mortality, for the same regulatory lab tests as are currently in use, thus virtually eliminating the concerns for sensitivity and accuracy associated with live tests using other tissues or lab protocols.

 

Preliminary regulatory reviews indicate that the VERGE procedure may be employed under 9 Code of Federal Regulations 55.8, as implemented by USDA CWD Program Standards (May 2014). The VERGE group has done preliminary work on implementation guidelines for an effective live test to allow integration of the live test option into existing programs and standards for both trace-forward/trace-back and herd certification and management programs, as well as refinement and development work for rapid training and wide-spread deployment to Industry.

 

RESOLUTION:

 

The United States Animal Health Association (USAHA) urges the United States Department of Agriculture (USDA), Animal and Plant Health Inspection Service (APHIS), Veterinary Services (VS) as well as state animal health officials to continue and to expedite discussions and evaluation of ante-mortem collection procedures for medial retropharyngeal lymph node (MRPLN) tissues for the live testing for chronic wasting disease (CWD) in white-tailed deer. USAHA also urges USDA-APHIS-VS to issue a VS

 

REPORT OF THE COMMITTEE

 

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Guidance Document stating that ante-mortem collection procedures for MRPLN tissues are acceptable and authorized in accordance with current federal regulations (9 Code of Federal Regulations (CFR) 55 and 9 CFR 81) and existing federal CWD Program Standards (MAY 2014).

 

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Chronic Wasting Disease Research and Updates in Colorado Michael Miller, Colorado Division of Parks and Wildlife

 

Dr. Michael Miller, Colorado Division of Parks and Wildlife, led a brief discussion on the implications of a recent study on chronic wasting disease (CWD) host range. The Case Western study results, presented at an international prion conference in May 2015, complement other efforts to assess human susceptibility to chronic wasting disease that have been ongoing since the mid-1990s. Findings from a variety of experimental and epidemiological studies support messaging since the mid-1990s that human illness resulting from CWD exposure appears unlikely. The new study’s results are consistent with other previous and contemporary data suggesting a low probability of human prion disease resulting from CWD exposure. Dr. Miller noted that even though human illness seems unlikely, minimizing the occurrence of CWD and encouraging other precautions for minimizing human exposure to CWD may be prudent. Trends observed in Colorado since 2002 suggest increasing infection rates in affected mule deer and elk herds, with the exception of one population unit intensively managed through harvest in the early 2000s. Controlling CWD will likely need to rely on hunting in order to remain politically, socially, and fiscally sustainable. Consequently, early intervention, while infection rates are still low, may offer the best opportunity to both suppress epidemics and minimize the likelihood of hunters harvesting infected animals. Dr. Miller suggested that the timing and approaches to CWD control may deserve more attention and reconsideration than given in recent years.

 

Summary of Recent Chronic Wasting Disease Events in Texas Mitch Lockwood, Texas Parks and Wildlife Department

 

Other contributing authors: Bob Ditmar Texas Parks and Wildlife Department, Andy Schwartz, Texas Animal Health Commission

 

Introduction:

 

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 3.9 million free-ranging white-tailed deer

 

 700K white-tailed deer hunters

 

 600K white-tailed deer harvested annually

 

 $3.6 billion economic output for all hunting

 

 $2.1 billion for deer hunting

 

 1,300 deer breeding facilities

 

 > 110,000 deer in breeding facilities

 

 > 2,200 free-ranging deer moved annually through various permits

 

Texas Parks and Wildlife Department (TPWD) has been conducting chronic wasting disease (CWD) surveillance throughout the state since 2002.

 

Biologists have collected more than 26,000 samples from hunter-harvested deer, and others have collected more than 21,000 samples in order to meet TPWD permitting requirements, totaling almost 48,000 samples. Additionally, Texas Animal Health Commission (TAHC) has maintained a Voluntary CWD Herd Certification Program since 1995.

 

In 2012, CWD was discovered in two mule deer samples from far West Texas (Hueco Mountains) as a result of a targeted surveillance effort. This area is directly adjacent to a region in New Mexico with documented CWD occurrence. To date, five more positive samples have been obtained from this population through hunter harvested mule deer, indicating a disease prevalence of 10%.

 

Mule deer and white-tailed deer are regulated by TPWD, while other susceptible species (including elk) are regulated by the TAHC. This has generated the need for enhanced coordination and communication between these two agencies.

 

The TPWD/TAHC CWD Management Plan was developed by both agencies in consultation with the state’s CWD Task Force. The Task Force is comprised of wildlife biologists, deer and elk breeders, veterinarians and other animal-health experts from TPWD, TAHC, Texas Veterinary Medical Diagnostic Laboratory, Texas Department of State Health Services, Texas A&M College of Veterinary Medicine, and USDA. The plan includes mandatory check stations for susceptible species taken inside the CWD Containment Zone, which covers portions of Hudspeth, Culberson, and El Paso counties. Artificial movement of deer is prohibited in the CWD Containment Zone.

 

On June 30, 2015 a sample from a Medina County (area on border of southern Edwards Plateau and northern South Texas Plains ecoregions) deer breeding facility was confirmed positive for CWD. The index breeding facility participated in TAHC’s voluntary CWD Herd Certification Program, and had tested 62 of 65 mortalities prior to June 2015 (60 not detected, two location results) since permitted in 2006. There were a total of 136 adult deer in the inventory on June 30, 2015, and the herd was considered to be relatively young.

 

During the previous five years, 107 deer were transferred from 30 deer breeding facilities into the index facility. During that same period, 835 were transferred from the index facility to 147 different facilities including 96 deer

 

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breeding facilities, 46 release sites, three Deer Management Permit (DMP) sites, and two sites in Mexico.

 

TPWD and TAHC immediately placed a temporary moratorium on movements of all captive deer in the state, and TAHC placed a Hold Order on the 177 “Tier 1” facilities. Since then, TPWD and TAHC worked with the CWD Task Force and industry stakeholders to develop a plan to lift the moratorium on deer transfers, which includes additional CWD testing requirements in deer breeding facilities or on registered release sites. Additionally, TAHC has removed the Hold Order for 120 facilities, leaving a total 57 facilities remaining under a Hold Order as of October 16, 2015. Most deer breeding facilities were authorized to transfer deer by August 24, 2015.

 

Depopulation at the index facility was initiated in July 28 and completed on September 30, 2015. CWD was detected in a total of 4 (out of 136 adults) white-tailed deer in the index facility, all of which were 2-year-old bucks that were natural additions.

 

On September 15, 2015, CWD was confirmed in one of the trace-forward facilities, from which 84 deer had transferred out to nine different facilities (five deer breeding facilities, three release sites, and one nursing facility) since it received deer from the index herd. This resulted in seven additional Hold Orders being issued by TAHC, four of which have since been released. The CWD-positive at the trace-forward facility was also a 2-year-old buck that was born in the index facility.

 

In summary, CWD has been detected in a total of five captive white-tailed deer in Texas, four of which were located in the index facility, and one was located in a trace-forward facility. There are 36 deer from the 2-year-old cohort originating in the index facility that are reported to be alive in seven deer breeding facilities, and possibly as many as six deer from that cohort still alive on release sites. Additionally, there are 33 deer that traced through the index facility that are still alive in 15 deer breeding facilities, and possibly as many as 51 trace-through deer are still alive on 24 different release sites,

 

***and two tracethrough deer may still be alive in Mexico.

 

TPWD has intensified the statewide CWD surveillance efforts, with a goal to collect samples from more than 8,000 hunter-harvested deer, including 300 samples within a 5-mile radius of the index facility. TAHC will continue to pursue indemnity on exposed deer located in trace-forward facilities in an attempt to conduct a more thorough epidemiological investigation. TPWD and TAHC have committed to reevaluate movement qualification standards that apply to deer breeding facilities and release sites following the 2015-16 hunting season. Both agencies are exploring ante-mortem testing protocols, and will continue to seek guidance from experts in the field.

 

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Epidemiology of Recent CWD Cases in Ohio

 

Susan Skorupski, USDA-APHIS-VS

 

Background

 

Ohio has had a voluntary Chronic Wasting Disease (CWD) Herd Certification Program for all cervidae for at least 12 years. Ohio has 331 cervidae herds in the CWD monitoring program with 256 at Certified level. In October 2012, Ohio White Tail Deer rule became effective. It includes several categories of white tail deer operations. Monitored herds cannot sell or give away animals and includes hunting preserves. Under this rule, hunting preserves cannot move live animals from the premises and must annually sample 30 animals or 30% of harvested deer, based on the number of deer harvested during the previous year. Herds with Status are herds enrolled in the CWD Certification Program but not yet at certified level. Certified Status Herds are enrolled in the CWD monitoring program and have reached certified status. Ohio has 135 Monitored Herds, including 24 hunting preserves, 75 Herds with Status, and 256 Certified Status herds.

 

Ohio’s approach to infected animals and associated animals and herds Infected herd – herd where a CWD infected animal resided when the test positive sample was collected. Herd quarantined.

 

Exposed herd – any herd where an animal that tested CWD positive has resided within the five years before the CWD diagnosis. Whole herd quarantined

 

Herd that contains an exposed animal – whole herd quarantined unless epidemiology information suggests the animal is of lower risk of spreading CWD.

 

Exposed animal – animal that was exposed to the CWD infected animal any time during the five years prior to when the animal died or was euthanized and sampled/tested positive for CWD.

 

Recent CWD History in Ohio

 

a. Pennsylvania traces

 

In the spring of 2014, Ohio received information on traces associated with CWD positive cases in Pennsylvania. Three Ohio herds were designated as Exposed herds because positive deer from infected herds in Pennsylvania had been in the Ohio herds during the previous five years. Fifty Ohio herds received 256 exposed deer from the five Pennsylvania herds and three Ohio exposed herds. Eighty-five of those animals were tested with Not Detected results in Ohio herds. Sixty-six animals were traced to Out of State herds. That leaves 101 animals either standing in quarantined herds or not tested when they died or were harvested. Eighteen herds/preserves remain under quarantine.

 

b. First CWD positive found in Ohio

 

On October 22, 2014, National Veterinary Services Laboratory (NVSL) confirmed a CWD positive result for a 2.5-year-old buck killed at a hunting preserve in Holmes County Ohio on October 2, 2014. The hunting preserve had been under quarantine since April 1, 2014 because of Pennsylvania traces and was required to do 100% sampling of harvested deer. The positive animal

 

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had official identification tracing the animal to a CWD certified Pennsylvania herd. Records including a Certificate of Veterinary Inspection (CVI) indicate the animal moved to Ohio March 13, 2013. Genetic testing was conducted to support the accuracy of the trace to the Pennsylvania herd. This herd was depopulated without indemnity April 27-29, 2015. Two hundred twenty-four animals were depopulated at owner expense and sampled for CWD. All tests had Not Detected results for CWD. The premises was evaluated as a minimally contaminated facility. No cervidae have been added to the premises at this time.

 

The owner of the hunting preserve business also owns or is associated with breeding herds at other locations in Holmes County.

 

c. Second positive premises in Ohio

 

A white tail deer breeding herd owned by the same person who owned the CWD positive hunting preserve was designated as a positive herd in the spring of 2015. A CWD positive animal was sampled on March 12, 2015 and reported on March 25, 2015. The animal was a five-year-old whitetail doe purchased from a Wisconsin herd in February 2013. A second CWD positive animal was reported from this herd on May 22, 2015. This animal was a 1.5- year-old natural addition doe.

 

This herd was initially established in the fall of 2012 with the purchase of a CWD certified herd from the estate of a deceased owner. In the spring and fall of 2013, additional animals were added from at least nine Ohio herds, one Wisconsin herd, 17 Pennsylvania herds, and three Indiana herds. This herd had been quarantined since April 1, 2014 because of traces from several CWD exposed or positive herds in Pennsylvania, including the herd that was the source of the CWD positive deer in the Ohio hunting preserve. It had received over 120 animals from these herds.

 

On June 15 and 16, this herd was depopulated with federal indemnity. Samples were collected for research purposes. Two hundred forty-one animals including 44 fawns were euthanized, sampled and tested. Sixteen additional positive were identified. They originated from five Ohio CWD certified herds and four Pennsylvania CWD certified herds. One of the Ohio herds was the herd that was used to initially establish this herd. One positive animal was over 60 months of age so that Ohio herd was not designated as an exposed herd. The other three Ohio herds were quarantined as exposed herds.

 

Records reviews identified 334 exposed animals associated with Ohio exposed herds. Forty-two Ohio herds containing these animals were quarantined. They have remained under quarantine until the quarantined animal(s) are euthanized and tested Not Detected for CWD or 60 months have passed since animals entered the herd. From Ohio Exposed Herd 1, 56 animals moved to 21 Ohio herds and 83 animals moved out of state. Twentyseven animals were either already dead and tested with CWD Not Detected results or have since been tested with CWD Not Detected results. From Ohio Exposed Herd 2, 76 animals moved to 16 Ohio herds and 94 animals moved out of state. Twenty-five animals were either already dead and tested with

 

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CWD Not Detected results or have since been tested with CWD Not Detected results. From Oho Exposed Herd 3, 21 animals moved to five Ohio herds and four animals moved out of state. Seven animals were either already dead and tested with CWD Not Detected results or have since been tested with CWD Not Detected results. Ohio received two exposed animals from the exposed herd in Pennsylvania associated with this case. In summary, 334 exposed animals were identified and traced to 40 Ohio herds. Fifty-nine of those in Ohio have been tested with Not Detected CWD results. One hundred eighty-one have been traced out of state and 94 are still standing in 26 quarantined herds/hunting preserves.

 

Ohio Exposed Herd 1 has been in the CWD Certification Program since September 2003 and has an inventory as of 48 head over one-year-old. Ohio Exposed Herd 2 has been in the CWD Certification Program since October 2003 and has an inventory of 93 animals. Ohio Exposed Herd 3 has been in the CWD Certification Program since February 2009 but started with a status date of May 2001 and has an inventory of 17 deer.

 

In addition, Ohio received reports of 72 exposed deer from out of state (OOS) Exposed herds traced to 18 Ohio herds. Eighteen of those animals had moved to out of state herds. Thirty animals were tested in Ohio with Not Detected results. Twelve animals remain in Seven quarantined herds. The summary of all traces associated with positive cases in Ohio and Pennsylvania in 2014 – 2015 are:

 

 Total exposed animals traced to Ohio: 661

 

 Total tested Not Detected: 176

 

 Total animals traced to Out of State Premises: 265

 

 Total premises initially quarantined: 87

 

 Total premises remaining quarantined: 40

 

 Total Hunting Preserves quarantined: 10

 

USDA Cervid Health Program Updates

 

Randy Pritchard, USDA-APHIS, Veterinary Services (VS)

 

Voluntary Chronic Wasting Disease (CWD) Herd Certification Program

 

The APHIS National CWD Herd Certification Program (HCP) was implemented in 2014. It is a voluntary Federal-State-industry cooperative program administered by APHIS and implemented by participating States. The program provides uniform national herd certification standards that minimize the risk of spreading CWD in farmed cervid populations. Participating States and herd owners must comply with requirements for animal identification, fencing, recordkeeping, inspections/inventories, as well as animal mortality testing and response to any CWD-exposed, suspect, and positive herds. APHIS monitors the Approved State HCPs to ensure consistency with Federal standards through annual reporting by the States. With each year of successful surveillance, participating herds will advance in status until reaching five years with no evidence of CWD, at which time herds are certified as being low-risk for CWD. Only captive cervids from enrolled herds certified as low risk for CWD may move interstate. Currently, 30 States participate in the voluntary CWD

 

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Herd Certification Program; 29 have Approved HCPs and one has Provisional Approved status. VS is working with the remaining State to transition it to Approved status. FY2015 marks the second year that Approved States have submitted their CWD HCP annual reports to APHIS. APHIS is currently reviewing these reports.

 

Review of CWD Program Standards

 

The CWD Program Standards provide clarification and guidance on how to meet CWD Herd Certification Program and interstate movement requirements. VS committed to an annual review of the Program Standards by representatives of the cervid industry and appropriate State and Federal agencies. VS planned to perform a review in FY2015; however, this did not occur due to the response to highly pathogenic avian influenza (HPAI). VS expects to conduct a review in FY2016.

 

CWD in Farmed and Wild Cervids

 

Retrospective Epidemiology of CWD in Farmed Cervids: In response to a 2014 USAHA Resolution, VS asked States to include a retrospective summary of the epidemiology of all positive herds with their annual HCP reports for FY2015. Unfortunately, the response to HPAI delayed completion of this summary. Five States reported information to date. A few States indicated that they did not have the resources to devote to this request. VS will continue to gather this data and to collect more comprehensive data in the future. Summary of CWD detections. As of September 30, 2015, CWD has been confirmed in wild deer and elk in 21 US States, and in farmed cervids in 16 States. In total, 23 States have identified CWD in wild and/or farmed cervids.

 

CWD has been reported in 70 farmed cervid herds in the United States.

 

Confirmation of the disease in three free-ranging, wild white-tailed deer in Michigan in 2015 marked the first report of CWD in the wild cervid population in this State.

 

FY2015 CWD Detections in Farmed Cervids: In FY2015, CWD was identified in eight farmed cervid herds: one white-tailed deer breeding herd in Pennsylvania, one elk breeding herd in Utah (traced back from a hunting facility in Utah), one white-tailed deer (WTD) breeding herd and one WTD hunting preserve in Ohio (owned by the same producer), two WTD breeding herds in Wisconsin, one WTD and elk herd in Texas, and a second WTD herd in Texas (traced from the first positive herd in Texas). The positive animals in Utah, Ohio, and Texas represented the first reported cases of CWD in captive cervids in all three of these States.

 

White-Tailed Deer Breeding Herd, Pennsylvania: On October 6, 2014, the National Veterinary Services Laboratories (NVSL) confirmed CWD in a 6- year-old doe from a captive WTD breeding facility in Reynoldsville, Pennsylvania. The doe was euthanized and tested because she was classified as a CWD-exposed animal that had previously resided in two trace back exposed herds. This herd was assembled in 2013 through the purchase of 16 animals from other HCP-certified herds in Pennsylvania, and had been under quarantine for receiving exposed animals from a trace back exposed herd. The remaining herd of eight WTD was depopulated with Federal indemnity on

 

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February 18, 2015, and no additional positive animals were detected. USDA collected samples for research purposes.

 

Elk Breeding Herd, Utah: On December 23, 2014, NVSL confirmed CWD in 3-year-old captive elk. The elk had been at a hunting park located in northern Utah, where he had resided for approximately three weeks prior to being hunter killed. All hunter-killed animals at the hunt park are required to be tested for CWD, and this animal was sampled through routine surveillance. The elk was traced back to its herd of origin, and that facility was quarantined. The herd was assembled in 1999 with bulls, and later elk cows, that originated from Colorado. Historical testing records for the herd were unavailable. The remaining 70 elk were depopulated using Federal indemnity funds on March 3, 2015, and an additional 25 elk were confirmed as CWD-positive. USDA collected samples for research purposes.

 

White-Tailed Deer Hunting Preserve, Ohio: On October 22, 2014, NVSL confirmed CWD in a buck taken from a captive WTD deer hunting preserve in Ohio. This was the first time that CWD had been detected in Ohio. The preserve was tested as part of Ohio’s CWD monitoring program. The herd had been under quarantine since April 2014 because it was a trace-forward herd associated with a CWD-exposed herd in Pennsylvania. The positive animal was traced to its herd of origin, a captive WTD breeding herd in Pennsylvania, through DNA identity testing. On November 26, 2014, the Ohio State Veterinarian issued an Order of Destruction for animals on the hunting preserve. The State executed this Order on April 27-30, 2015. The herd of 224 WTD was depopulated and no other positives were detected. USDA did not provide Federal indemnity.

 

White-Tailed Deer Breeding Herd, Ohio: On March 31, 2015, NVSL confirmed CWD infection in a 5-year-old WTD doe from a captive breeding herd in Holmesville, Ohio. The index animal was received from a Wisconsin WTD farm in January 2013. The CWD-positive herd was owned by the same individual as the Ohio hunt preserve that was found to be CWD positive in October 2014. On May 22, 2015, NVSL confirmed a second positive case in the same herd -- a yearling WTD doe that was a natural addition in the same breeding herd. The herd had been under quarantine since April 1, 2014 due to epidemiological linkages with two WTD herds in Pennsylvania – one a positive herd and the other a traceback exposed herd. USDA provided Federal indemnity and depopulated this herd on June 15 and 16, 2015. USDA collected samples for research purposes. NVSL confirmed CWD in 16 additional animals in the herd. Of the 16 positives, one was natural addition and the rest were purchased additions. The positive animals were purchased from February 26, 2013 through September 24, 2013, except for one purchased in 2012. Eleven purchased additions traced-back to three herds in Pennsylvania and four purchased additions traced to three other herds in Ohio.

 

White-Tailed Deer Breeding Herd, Wisconsin:

 

On October 6, 2014, NVSL confirmed CWD in a 2-year-old doe born in June of 2012 that died on a Richland County farm. The facility is within the CWD management zone in Wisconsin. The remaining 51 deer were euthanized on November 20, 2014,

 

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and seven additional positives (all males born in 2012) were found. Two of these seven were purchased additions with the last added to the herd in January 2013. All sales from this herd were to shooting preserves. This premises was double fenced and had been compliant in a herd certification program for over ten years.

 

White-Tailed Deer Breeding Herd, Wisconsin: On June 19, 2015, NVSL confirmed CWD in a 7-year-old female WTD from a breeding facility in Eau Claire County. The doe was a natural addition to this breeding herd. This is the first positive CWD case, captive or wild, in this county. The doe was found dead and was showing no clinical signs of CWD at the time of death. Since 2003, this herd has tested 391 animals for CWD and all had “not detected” results. In addition, 317 animals have tested “not detected” from the associated hunting preserve over the same time period. A second positive natural addition doe from this herd was confirmed positive by NVSL on September 10, 2015. Several escape episodes have occurred from this herd. The herd is currently under quarantine and plans are underway for depopulation with State indemnity.

 

White-Tailed Deer and Elk Breeding Herd, Texas:

 

On June 30, 2015, NVSL confirmed CWD in a 2-year-old WTD buck from a captive WTD and elk breeding herd in Medina County, Texas, approximately 500 miles from previously reported positive free-ranging mule deer in far West Texas. This was the first time that the disease had been detected in farmed cervids in the State. The index buck was born on the premises and found dead on June 18, 2015. Over 40 high-risk deer (i.e., pen mates, dam, others) were euthanized and tested after the index case was found. The NVSL confirmed CWD infection in two of those deer. Interestingly, all three of the positive deer identified to date on this premises have the same AI sire. However, the significance of this finding is unclear. In the past five years, records indicate that 130 WTD from 33 facilities moved into the positive herd and 838 WTD moved out of the positive herd to 147 different herds. One positive WTD was found in one of these traceout herds (see herd description below). Additionally, 23 elk were also moved from this herd to another herd in Texas in 2014. All trace-outs have been intrastate except for movements to two premises in Mexico. Premises that have received deer from the index herd are under movement restrictions. VS is collaborating with animal health authorities in Mexico. VS paid indemnity and depopulated this herd on September 30, 2015, and no additional positive animals were detected. USDA collected samples for research purposes. White-Tailed Deer Herd, Texas: On September 14, 2015 NVSL confirmed CWD from tissues from a WTD in Lavaca County, Texas. This animal was a traceout from the first CWD positive herd from June 30, 2015. Additional epidemiology is ongoing.

 

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Cervid Health Program Budget

 

The Cervid Health Program includes the CWD herd certification program and the cervid TB program. It is funded through the Equine, Cervid, and Small Ruminant Line Item. In FY2015, the Cervid Health Program was appropriated $3.0 million by Congress for cervid health activities. This funding was allocated as follows:

 

 Indemnity − $1.1 million for CWD and cervid TB (an additional $230,000 was provided to support herd depopulation activities in Texas).

 

 CWD Research − $200,000 to support USDA Wildlife Services (WS) research for development of CWD live animal diagnostic testing.

 

 Cervid Health Program − $1.2 million for general program support (primarily field activities).

 

APHIS anticipates the FY2016 Cervid Health Program funding will remain at FY2015 levels.

 

Committee Business:

 

One resolution was proposed by a committee member titled Chronic Wasting Disease Testing Protocol for Wild Cervidae proposing the United States Animal Health Association (USAHA) urge the USDA to amend CFR 81.3 (b); proposing wild cervids captured for interstate movement and release, have two forms of identification, one of which that is official identification, must be PrP genotyped for chronic wasting disease resistance, tested for chronic wasting disease using a rectal biopsy test. The committee discussed and debated the terms and science related to this resolution proposal including that currently there is no science indicating there are “genotype resistant” cervids to acquiring the CWD prion. The term “resistant” is miss-leading. There are only different cervid genotypes that acquire the infectious prions at different rates and show clinical signs at variable rates, some at prolonged periods after acquiring the prion or they are slow to accumulate detectable levels. Since all infected animals would be presumed to be capable of shedding the prions into the environment, genotypes with clinical “resistance” or prolonged indication of clinical presentation of the disease, may well potentially be considered prolonged shedders of the prion. Additionally, there was discussion put forth by several committee members concerning the lack of regulatory validation of the rectal biopsy test. Also, the test can only be used on young animals and there is significant test sensitivity and specificity variability between cervid species when using this test. A new motion to the proposed resolution was to table this resolution, reword the resolution potentially to be a recommendation for USDA to provide a guidance document to the states for surveillance of CWD on interstate translocations of wild cervids. It was proposed that this new resolution/recommendation be discussed during the Farmed Cervid Subcommittee and forward then to the Committee on Captive Wildlife and

 

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Alternative Livestock. The motion was proposed by member Charlie Seale and seconded by member Sean Shaffer which was passed by committee. The Committee on Wildlife Diseases adjourned at 5:15 p.m.

 

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NOMINATIONS AND RESOLUTIONS 291

 

RESOLUTION NUMBER: 13 APPROVED SOURCE: COMMITTEE ON SCRAPIE SUBJECT MATTER: SCRAPIE RULE BACKGROUND INFORMATION:

 

While the Scrapie Eradication Program has been very successful in decreasing the prevalence of scrapie in the United States, eradication has not yet been achieved in sheep or goats. Improved traceability and surveillance are needed to detect the last remaining cases of scrapie, proving to our trading partners that the United States is scrapie-free thus adding approximately $50 million in export value. Mandatory identification of sheep has allowed slaughter surveillance to be the key in reducing the prevalence of scrapie in sheep by 85%. Slaughter surveillance of goats has been problematic because currently only 50% of mature goats are officially identified at slaughter, making it impossible to conduct effective surveillance. A proposed rule to amend 9 Code of Federal Regulations Parts 54 and 79 has been published. This proposed rule addresses new standards for official identification and traceability for goats as well as other gaps in the regulation. To succeed in the eradication of scrapie, it is imperative that this rule be promptly finalized after appropriate review and consideration of comments.

 

RESOLUTION:

 

The United States Animal Health Association urges the United States Secretary of Agriculture to publish a final scrapie rule in early 2016. The proposed rule, which provides for improved traceability for goats and addresses other gaps in the current regulation, is a critically important element needed to achieve scrapie eradication in the United States.

 

*****

 

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REPORT OF THE COMMITTEE ON SCRAPIE

 

Chair: Kristine Petrini, MN Vice Chair: Cheryl Miller, IN James Averill, MI; Scott Bender, AZ; Deborah Brennan, MS; Minden Buswell, WA; Beth Carlson, ND; John Clifford, DC; Walter Cook, TX; Stephen Crawford, NH; Susan Culp, TX; Ignacio dela Cruz, MP; William Edmiston, TX; Anita Edmondson, CA; Dee Ellis, TX; Keith Forbes, NV; Larry Forgey, MO; Michael Gilsdorf, MD; William Hartmann, MN; Carl Heckendorf, CO; Amy Hendrickson, WY; Russell Iselt, TX; Paul Jones, AL; Susan Keller, ND; Eileen Kuhlmann, MN; James Leafstedt, SD; Mary Lis, CT; Jim Logan, WY; Shirley McKenzie, NC; Ronald Miller, PA; Elisabeth Patton, WI; Jewell Plumley, WV; Justin Roach, OK; Suelee Robbe-Austerman, IA; Paul Rodgers, WV; Susan Rollo, TX; Joan Dean Rowe, CA; Ben Smith, WA; Scott Stuart, CO; Diane Sutton, MD; Manoel Tamassia, NJ; Jeff Turner, TX; Stephen White, WA; Nora Wineland, MO; David Winters, TX; Cindy Wolf, MN.

 

The Committee met on October 27, 2015 in Room 553 of the Rhode Island Convention Center in Providence, Rhode Island from 9:00 a.m. to 12:06 p.m. There were 18 members and 20 guests present.

 

Time-Specific Paper

 

Dr. Diane Sutton, presented a time-specific paper on the Newly Published Proposed Revisions to Scrapie Rules 9 CFR, parts 54 and 79. Dr. Sutton summarized the changes and explained the process for submitting comments. The Committee discussed some of the highlights of the proposed changes. A full summary is included at the end of this report.

 

Presentations and Reports

 

USDA-APHIS Scrapie Program Update and Scrapie Surveillance Projects Diane Sutton, USDA-APHIS, Veterinary Services (VS)

 

Scrapie Eradication Program Results

 

 The National Scrapie Eradication Program continued to make progress in FY2015.

 

 At the end of FY2014, the percent of cull sheep found positive at slaughter and adjusted for face color was 0.018 percent and is currently at 0.004 percent for FY 2015. This measure has decreased by 80 percent compared to FY2014 and by 98 percent compared to FY2003.

 

 Three source flocks and three infected flocks were designated in FY2014. One infected and three source flocks have been designated in FY2015, a decrease of 30 percent.

 

 In November 2014, the first positive goat found through regulatory scrapie slaughter surveillance (RSSS) was identified. Based on the goats sampled at slaughter to date, the prevalence of scrapie in US cull goats (2003 –

 

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2015) was 0.0037 percent with an upper 95 percent confidence limit of 0.0097 percent.

 

 In FY2015 there was a decrease in the number of States meeting their sampling minimums for sheep and goats. This was likely due in part to the impact of highly pathogenic avian influenza (HPAI) response on resources.

 

Slaughter Surveillance

 

As of September 30, 2015, 40,862 animals were sampled for scrapie testing in FY2015:

 

• 38,671 RSSS samples and 2,191 on-farm samples;

 

• Of which 33,698 were sheep and 7,164 were goats.

 

Scrapie Surveillance Plan

 

 Implementation FY2016

 

o States with RSSS collection sites will continue to sample all targeted sheep and goats.

 

o The annual State-of-origin sampling minimum for sheep is 20 percent of the number required to detect a scrapie prevalence of 0.1 percent with 95 percent confidence or 1 percent of the breeding flock in the State, whichever is less. The objective is to sample sufficient sheep in a 5-year period to detect a scrapie prevalence of 0.1 percent with 95 percent confidence or 5 percent of the breeding flock in the State, whichever is less.

 

o The annual State-of-origin sampling minimum for goats is determined based on the States’ goat scrapie case incidence.

 

o If a State has not had a goat scrapie case in the previous ten years, its annual goat sampling minimum is its prorated share of 3,000 samples, based on its proportion of the US goat population as determined by the National Agricultural Statistics Service (NASS) Sheep and Goat annual report.

 

o If a State has had a goat scrapie case in the previous ten years, its annual goat sampling minimum is determined using the same method as is used for determining its annual sheep sampling minimum.

 

Note: These are minimums. Plan is to continue to collect samples from the maximum number of targeted animals given the available budget.

 

ID Compliance:

 

 All scrapie positive animals in FY2015 were traced back to their flock of origin.

 

Proposed Rules Planned for Publication:

 

 VS published revisions to nine Code of Federal Regulations (CFR) parts 54 and 79. The proposed changes are intended to improving the effectiveness and cost efficiency of surveillance and to increase animal identification compliance by addressing gaps in identification and by requiring States to meet reasonable surveillance targets to remain consistent States. States must meet these targets for VS to demonstrate geographically appropriate surveillance to meet the criteria for freedom and have confidence that all of the remaining cases have been found.

 

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 The rule would propose to:

 

o Give the APHIS Administrator authority to relieve requirements for sheep and goats exposed to scrapie types, such as Nor98-like, that do not pose a significant risk of transmission;

 

o Increase flexibility in how investigations can be conducted and allow the epidemiology in a specific flock to be given more consideration in determining flock and animal status;

 

o Add a genetic-based approach to regulation;

 

o Make goat identification requirements similar to those for sheep to support ongoing slaughter surveillance in goats (no changes will be made in the consistent State requirements regarding identification of goats in intrastate commerce);

 

o Tighten the definition of slaughter channels;

 

o Expand the individual identification requirement to all sexually intact animals unless moving as a group/lot (allows mixed-source groups moving in slaughter channels at under 18 months);

 

o Limit the use of tattoos and implants to animals not moving through markets and not in slaughter channels; and

 

o Reduce recordkeeping requirements by making them similar to the current uniform methods and rules compliance guidance.  APHIS is also revising its scrapie import regulations to bring them more in line with the OIE scrapie chapter. This will ensure that we meet OIE criteria for free status and prevent the reintroduction of scrapie after free status is achieved.

 

Scrapie Flock Certification Program (SFCP)  Implementation of the revised Scrapie Flock Certification Program (SFCP) in FY 2014 has increased the efficacy of the program while reducing program costs.

 

 At the end of FY2015 there were 441 producers enrolled in the program.

 

TSE: An Update

 

Linda Detwiler, Department of Pathobiology and Population Medicine, Mississippi State University, College of Veterinary Medicine Dr. Detwiler reviewed and discussed recent transmissible spongiform encephalopathy research relevant to scrapie.

 

Update on Scrapie Research from the Animal Disease Research Unit David Schneider, Animal Disease Research Unit, Agricultural Research Service (ARS), USDA

 

The USDA-ARS unit in Pullman, Washington, conducts an integrated research program involving studies on scrapie diagnostics, the role of prion protein (PRNP) genetics, and modes of transmission in domestic sheep and goats. In this update, we report on a comparison between sheep and goats on factors that affect the diagnostic quality of rectal biopsy; progress on determination of the role of PRNP genetics on the susceptibility, disease progression, and impact on diagnostics in goats inoculated with classical

 

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scrapie; progress in evaluating potential modes of transmission for atypical (Nor98-like) scrapie in sheep and classical scrapie via goat’s milk; and use of mouse models to discriminate sheep and goats with classical scrapie versus experimental chronic wasting disease.

 

Biopsy of the rectal mucosa is a sensitive and safe technique used worldwide in the live-animal diagnosis of classical scrapie infection in sheep and goats, but which is sometimes limited when biopsy samples contain insufficient follicles. Reported rates of biopsies with insufficient follicles have ranged from 3% to 33%, with a significantly higher rate reported in goats and indicating the number of follicles may depend on both procedural and animal factors. Using live-animal biopsies obtained from a cohort of research sheep and goats, we determined that laboratory handling had a minor effect on the number of the follicles observed in each section. The most important factor was the animal’s age at the time of biopsy, decreasing at a steady rate of 13 percent per year during the first four years of the animal’s life. There was no left versus right side difference in the age-related decline in follicle number and the findings were the same between sheep and goats.

 

Regarding prion protein genetics, we continue to monitor goats of different genotypes orally inoculated at birth with classical scrapie prions derived from naturally infected goats. Goats with the highly susceptible genotype all developed clinical disease within 24 months. Goats with the less susceptible or long incubation genetics (S146 or K222) have remained clinically normal with no evidence of prions in rectal biopsy tissues. These goats will be monitored for the duration of the natural lifespan. In addition, a related study was completed which demonstrates a doubly prolonged incubation period in inoculated goats bearing the GS127 polymorphism.

 

Regarding our studies on modes of prion transmission, we very recently completed and are finalizing analyses for a 7-year study on Nor98-like scrapie in breeding ewes. Ewes were experimentally inoculated with brain homogenate obtained from a US sheep with clinical Nor98-like scrapie. Recipient ewes were bred annually to examine the placenta for evidence of a transmissible agent. One recipient ewe developed an unrelated disease in her fifth year of scrapie incubation. At postmortem examination, a Nor98-like pattern of misfolded prion protein, PrP-Sc, accumulation was observed. Similar findings were recently confirmed through postmortem examination of the other three ewes in the seventh year of scrapie incubation. These results confirm that inoculation of these ewes was successful. Not all placental tissue analyses have yet been completed, but there has been no evidence of placental accumulation of PrP-Sc out to the sixth year of infection.

 

We have recently confirmed that the classical scrapie prions which accumulate in the placenta of goats are infectious to sheep. Similarly, transmission to sheep has also occurred via the milk of infected goats. Thus, both the placenta and milk of infected goats are significant transmission risks to sheep.

 

Finally, we are nearing the completion of a study to determine if transgenic mice can be used to differentiate the origin of prions in new cases of scrapie

 

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disease in sheep and goats raised in regions with endemic chronic wasting disease (CWD) in cervids. The results show that transgenic mice bearing a susceptible prion protein are readily susceptible to classical scrapie prions derived from naturally infected sheep and goats but not to CWD prions derived from naturally infected cervids. The converse was true for transgenic mice bearing a susceptible cervid prion protein. Both types of mice were only intermediately susceptible to CWD prions derived from experimentally infected sheep. Thus, to date, the results suggest this bioassay model can discriminate between these sources of prions in new cases of prion disease in small ruminants from regions in which CWD is endemic in cervid populations.

 

Committee Business:

 

The Committee reviewed its mission statement and no alterations were suggested. There was a discussion about whether the Committee on Scrapie and the Committee on Sheep and Goats should be combined. The Committee members indicated that at this time the two committees should remain separate.

 

The Committee reviewed its 2014 Resolution that urged the Secretary of Agriculture to quickly publish and finalize the proposed rule amending 9 CFR Parts 54 and 79. This proposed rule is now published and open for public comment. The Committee passed a new resolution urging the Secretary of Agriculture to promptly publish a final scrapie rule in early 2016 following the appropriate review and comment period.

 

Note: Prior to the Committee on Scrapie meeting the following presentation was given by Dr. Diane Sutton as part of the National Scrapie Oversight Board meeting. A summary is included below supplemental to the Committee Report.

 

SFCP Participation

 

 As of September 30, 2015 there were 441 participating flocks in the SFCP.

 

o 277 Select Monitored

 

o 142 Export Monitored

 

o 22 Export Certified

 

 In FY2015 four Export Monitored flocks advanced to Export Certified.

 

 48 sheep breeds and 17 goat breeds are represented in the SFCP.

 

 As of September 30, 2015 there are active State SFCP boards in nine States.

 

Canada’s Import Requirements

 

 APHIS still anticipates a change in Canada’s import requirements, exact timeline of publication of new requirements not yet determined.

 

 The change will be an increase in the minimum time in status in the Export Category for eligibility to import US sheep or Goats into Canada.

 

Export Monitored Flock FY 2015 Review

 

 Export Monitored flocks in Standard or Alternative two sampling protocols must meet sampling thresholds to reach six years of status (Standard=15; Alternative 2=at least 50% foundation flock). In June 2015 Export

 

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Monitored flocks with six or more years of status were reviewed. Ninety-six flocks were reviewed, and of these:

 

o APHIS identified 28 flocks with six or more years of status that had not met the sampling threshold;

 

o The status dates for these flocks were reset to five years; and

 

o Notification letters were sent to producers explaining their new status dates and steps they can take to regain six years of status by January 1, 2016.  APHIS will continue to monitor flocks that are approaching six years. They must meet threshold and notify those that need to take action to maintain their status date.

 

Select Category

 

 Participation in the Select category was lower in FY2015 than in FY2014.

 

 APHIS’ goal in FY2016 is to increase participation in this category, thereby increasing the SFCP contribution to scrapie on-farm surveillance.

 

 APHIS will also review Select Monitored flocks in FY2016 for compliance with sampling requirements.

 

SFCP Standards

 

In FY2015, APHIS revised the SFCP Standards. The revised standards are currently in clearance and are expected to be published in FY2016.

 

Updates to the SFCP Standards included the following items:

 

 In the Select category, animals collected through Regulatory Scrapie Slaughter Surveillance (RSSS) will count toward the sampling requirement if at least ten animals are collected through RSSS in the same sampling period.

 

 Sampling requirements in genetically resistant Export Monitored flocks following the Standard sampling protocol: if there are no genetically susceptible animals in the flock (i.e. the flock is composed entirely of QR/RR ewes, RR rams, and no goats), the annual, 6-year, and 7-year sampling requirements are waived (assuming all other sampling requirements are met).

 

 Criteria for exempting lambs born in genetically resistant flocks from genotyping for Standard and Alternative 1 sampling protocol: if there are no genetically susceptible animals in the flock and the owner only has mature RR rams on the premises from that point forward lambs do not need to be genotyped. Note: these conditions will be confirmed at each subsequent annual inspection, and if an inspector believes at any time that one or more of the animals in the flock may be a QQ animal, the inspector will require that the animal(s) be officially genotyped.

 

 How to treat “Lost to Inventory” animals in Export Monitored flocks following the Alternative 1 sampling protocol:

 

o The flock owner may elect to switch to the standard sampling protocol, and the flock’s status date will be reset to the lesser of the flock’s current status date or 12 months of status for each test eligible animal sampled and must meet the additional sampling

 

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requirements of the standard sampling protocol to retain more than five years in status; or

 

o The flock owner may elect to stay in the Alternative 1 category, and the flock’s status date will be reset to the date the VS office was notified (or the lost to inventory animal became known to the VS office) that the animal was lost to inventory.

 

 Animals from Inconsistent States not in slaughter channels must be from either an Export Monitored/Export Certified flock or from a Select Monitored flock in which it was born. There are no changes for animals in slaughter channels.

 

 Retesting animals to meet the annual sampling requirement:

 

o If a flock following the Standard sampling protocol has live-animal tested all genetically susceptible test eligible animals at least once and must test an additional animal to meet the annual sampling requirement, previously tested animals can be repeat live-animal tested.

 

o If all genetically susceptible animals in the flock have been live animal tested four times, the annual sampling requirement is waived.

 

 Export category flocks must report the use of milk/colostrum from a lower status flock.

 

 Animals tested within 12 months of another animal being “Lost to Inventory” can meet the lost to inventory sampling requirement in Export Certified flocks if the flock had already tested 30 animals (this does not apply to “Found Dead” animals).

 

 How to treat previously live-animal tested “Found Dead” and “Lost to Inventory” animals in Export Monitored flocks:

 

o Lost to inventory – if the animal had been tested in the previous 12 months, no change in status and no additional animals need to be tested (and if the flock is following the Alternative 1 sampling protocol it does not have to switch to the Standard sampling protocol).

 

o Found dead – APHIS will determine if the animal reasonably could have been sampled. If so, the animal will be treated as any other found dead. If not the animal is considered lost to inventory and will treated the same as other lost to inventory animals.

 

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REVIEW AND DISCUSSION OF NEWLY PUBLISHED REVISIONS TO SCRAPIE RULES 9 CFR, PARTS 54 AND 7

 

Diane Sutton

 

USDA-APHIS-Veterinary Services (VS)

 

Overview

 

The US Department of Agriculture’s (USDA) Animal and Plant Health Inspection Service (APHIS) is proposing changes to its existing scrapie regulations. Scrapie is a degenerative and eventually fatal prion disease of sheep and goats, and APHIS regulations help prevent its spread and support its eventual eradication.

 

This is a synopsis of the proposed rule and should not be considered definitive. Please read the entire proposed rule

 

http://www.regulations.gov/#!docketDetail;D=APHIS-2007-0127

 

to review all the proposed changes as well as APHIS’ reasons for the proposed changes. Also, please read the draft “Scrapie Program Standards, Volume 1: National Scrapie Eradication Program” which is also posted at the link above. The rule proposes to:

 

1. Remove the low-risk commercial goat exemption and treat sheep and goats the same with respect to official identification requirements, the only differences are the allowed state exemptions which have not been changed.

 

2. Simplify the way the identification and movement requirements are presented and clarify the requirements. Also, adds tag replacement and use requirements from the ADT rule. Recommend reading proposed §79.2 and 79.3 in their entirety.

 

3. Add “Free” to “Scrapie Flock Certification Program” to read “Scrapie Free Flock Certification Program”

 

4. Change the noncompliant definition so that it now reads: Noncompliant flock. (1) Any source, infected, or exposed flock or flock under investigation whose owner declines to enter into a flock plan or post-exposure management and monitoring plan agreement within 30 days of being so designated, or whose owner is not in compliance with either agreement;

 

(2) Any exposed flock or flock under investigation whose owner fails to make animals available for testing within 60 days of notification, or as mutually agreed, or whose owner fails to submit required postmortem samples;

 

(3) Any flock whose owner has misrepresented, or who employs a person who has misrepresented, the scrapie status of an animal or any other information on a certificate, permit, owner statement, or other official document within the last 5 years; or

 

(4) Any flock whose owner or manager has moved, or who employs a person who has moved, an animal in violation of this chapter within the last 5 years.

 

5. Remove concept of “separate contemporary lambing group”.

 

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6. Change certificate to Interstate Certificate of Veterinary Inspection (ICVI). See proposed § 79.5 for ICVI requirements. Adds requirement for breeding animals that official genotype be included on the ICVI if known.

 

7. Change definition of flock sire to read: Flock sire. A sexually intact male animal that has produced offspring in the preceding 12 months or that was used for breeding during the current breeding cycle.

 

8. Change definition of scrapie positive animal to add ELISA Scrapie-positive animal. An animal for which a diagnosis of scrapie has been made by the National Veterinary Services Laboratories or another laboratory authorized by the Administrator to conduct scrapie tests in accordance with this chapter, through:

 

(1) Histopathological examination of central nervous system (CNS) tissues from the animal for characteristic microscopic lesions of scrapie;

 

(2) The use of proteinase-resistant protein analysis methods including but not limited to immunohistochemistry, and/or ELISA, and/or western blotting on CNS and/or peripheral tissue samples from a live or a dead animal for which a given method or combination of methods has been approved by the Administrator for use on that tissue;

 

(3) Bioassay;

 

(4) Scrapie associated fibrils (SAF) detected by electron microscopy; or

 

(5) Any other test method approved by the Administrator in accordance with §54.10 of this chapter.

 

9. Add the concept of “classification or reclassification investigation” and moves details for conducting them to the APHIS website in the program standards. See proposed § 79.4 and the draft program standards for more information.

 

Classification or reclassification investigation. An epidemiological investigation conducted or directed by a DSE for the purpose of designating or redesignating the status of a flock or animal. In conducting such an investigation, the DSE will evaluate the available records for flocks and individual animals and conduct or direct any testing needed to assess the status of a flock or animal. The status of an animal or flock will be determined based on the applicable definitions in this section and, when needed to make a designation under § 79.4 of this chapter, official genotype test results, exposure risk, scrapie type involved, and/or results of official scrapie testing on live or dead animals

 

10. Changes definition of destroy, removes slaughter option for indemnified animals

 

Destroyed. Euthanized and the carcass disposed of by means authorized by the Administrator that will prevent its use as feed or food,

 

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or moved to a quarantined research facility if the movement has been approved by the Administrator.

 

11. Change exposed animal definition:

 

a. Adds embryo explicitly

 

b. Sets criteria for setting date of infection

 

c. Adds concept of further designation based on genotype and exposure risk.

 

Exposed animal. Any animal or embryo that: (1) Has been in a flock or in an enclosure off the premises of the flock with a scrapie-positive female animal, (2) resides in a noncompliant flock, or (3) has resided on the premises of a flock before or while it was designated an infected or source flock and before a flock plan was completed. An animal shall not be designated an exposed animal if it only resided on the premises before the date that infection was most likely introduced to the premises as determined by a Federal or State representative. If the probable date of infection cannot be determined based on the epidemiologic investigation, a date 2 years before the birth of the oldest scrapie-positive animal(s) will be used. If the actual birth date is unknown, the date of birth will be estimated based on examination of the teeth and any available records. If an age estimate cannot be made, the animal will be assumed to have been 48 months of age on the date samples were collected for scrapie diagnosis. Exposed animals will be further designated as genetically resistant exposed sheep, genetically less susceptible exposed sheep, genetically susceptible exposed animals, or low-risk exposed animals. An animal will no longer be an exposed animal if it is redesignated in accordance with § 79.4.

 

12. Redefine exposed flock (divides old definition into Flock Under Investigation and Exposed Flock and references redesignation section: Exposed flock. (1) Any flock that was designated an infected or source flock that has completed a flock plan and that retained a female genetically susceptible exposed animal; (2) Any flock under investigation that retains a female genetically susceptible exposed animal or a suspect animal, or whose owner declines to complete genotyping and live-animal and/or post-mortem scrapie testing required by the APHIS or State representative investigating the flock; or (3) Any noncompliant flock or any flock for which a PEMMP is required that is not in compliance with the conditions of the PEMMP. A flock will no longer be an exposed flock if it is redesignated in accordance with § 79.4 of this chapter.

 

Flock under investigation. Any flock in which an APHIS or State representative has determined that a scrapie-suspect animal, high-risk animal, or scrapie-positive animal resides or may have resided. A flock will no longer be a flock under investigation if it is redesignated in accordance with § 79.4 of this chapter.

 

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13. Add definitions for genetically less susceptible exposed sheep, genetically resistant exposed sheep, genetically resistant sheep, genetically susceptible animal, and genetically susceptible exposed animal.

 

Genetically less susceptible exposed sheep. Any sheep or sheep embryo that is:

 

(1) An exposed sheep or sheep embryo of genotype AA QR, unless it is epidemiologically linked to a scrapie-positive RR or AA QR sheep or to a scrapie type to which AA QR sheep are not less susceptible where Q represents any genotype other than R at codon 171; or

 

(2) An exposed sheep or sheep embryo of genotype AV QR, unless it is epidemiologically linked to a scrapie-positive RR or QR sheep, to a flock that the DSE has determined may be affected by valine associated scrapie (based on an evaluation of the genotypes of the scrapie-positive animals linked to the flock), or to another scrapie type to which AV QR sheep are not less susceptible where Q represents any genotype other than R at codon 171 and V represents any genotype other than A at codon 136; or

 

(3) An exposed sheep or sheep embryo of a genotype that has been exposed to a scrapie type to which the Administrator has determined that genotype is less susceptible.

 

Genetically resistant exposed sheep. Any exposed sheep or sheep embryo of genotype RR unless it is epidemiologically linked to a scrapie-positive RR sheep or to a scrapie type to which RR sheep are not resistant.

 

Genetically resistant sheep. Any sheep or sheep embryo of genotype RR unless it is epidemiologically linked to a scrapie-positive RR sheep or to a scrapie type that affects RR sheep.

 

Genetically susceptible animal. Any goat or goat embryo, sheep or sheep embryo of a genotype other than RR or QR, or sheep or sheep embryo of undetermined genotype where Q represents any genotype other than R at codon 171.

 

Genetically susceptible exposed animal. Excluding low-risk exposed animals, any exposed animal or embryo that is also: (1) A genetically susceptible animal.

 

(2) A sheep or sheep embryo of genotype AV QR that is epidemiologically linked to a scrapie-positive RR or QR sheep, to a flock that the DSE has determined may be affected by valine associated scrapie (based on an evaluation of the genotypes of the scrapie-positive animals linked to the flock), or to a scrapie type to which AV QR sheep are susceptible where Q represents any genotype other than R at codon 171 and V represents any genotype other than A at codon 136.

 

(3) A sheep or sheep embryo of genotype AA QR that is epidemiologically linked to a scrapie-positive RR or AA QR sheep or to

 

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a scrapie type to which AA QR sheep are susceptible where Q represents any genotype other than R at codon 171; or

 

(4) A sheep or sheep embryo of genotype RR that is epidemiologically linked to a scrapie-positive RR sheep or to a scrapie type to which RR sheep are susceptible.

 

14. High-risk animal redefined as. The female offspring or embryo of a scrapie-positive female animal, or any suspect animal, or a female genetically susceptible exposed animal, or any exposed animal that the Administrator determines to be a potential risk based on the scrapie type, the epidemiology of the flock or flocks with which it is epidemiologically linked, including genetics of the positive sheep, the prevalence of scrapie in the flock, any history of recurrent infection, and other flock characteristics. An animal will no longer be a high-risk animal if it is redesignated in accordance with § 79.4 of this chapter. This in concert with the new low-risk exposed animal definition below gives a lot of flexibility in handling infected/source flocks and exposed animals minimizing the need to revise the regulations as scientific knowledge increases. It also allows APHIS to not restrict animals exposed to Nor98-like scrapie and to at some point if warranted by new scientific evidence establish a genetic based approach for goats. Low-risk exposed animal. Any exposed animal to which the DSE has determined one or more of the following applies:

 

(1) The positive animal that was the source of exposure was not born in the flock and did not lamb in the flock or in an enclosure where the exposed animal resided;

 

(2) The Administrator and State representative concur that the animal is unlikely to be infected due to factors such as, but not limited to, where the animal resided or the time period the animal resided in the flock;

 

(3) The exposed animal is male and was not born in an infected or source flock;

 

(4) The exposed animal is a castrated male;

 

(5) The exposed animal is an embryo of a genetically resistant exposed sheep or a genetically less susceptible exposed sheep unless placed in a recipient that was a genetically susceptible exposed animal; or,

 

(6) The animal was exposed to a scrapie type and/or is of a genotype that the Administrator has determined poses low risk of scrapie transmission.

 

15. Change the first paragraph of the suspect animal definition to read:

 

(1) A mature sheep or goat as evidenced by eruption of the first incisor that has been condemned by FSIS or a State inspection authority for central nervous system (CNS) signs, or that exhibits any of the following clinical signs of scrapie and has been determined to be suspicious for scrapie by an accredited veterinarian or a State or USDA representative, based on one or more of the following signs and

 

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the severity of the signs: (i) Weakness of any kind including, but not limited to, stumbling, falling down, or having difficulty rising, not including those with visible traumatic injuries and no other signs of scrapie; (ii) behavioral abnormalities; (iii) significant weight loss despite retention of appetite or in an animal with adequate dentition; (iv) increased sensitivity to noise and sudden movement; (v) tremors; (vi) star gazing; (vii) head pressing; (viii) bilateral gait abnormalities such as but not limited to incoordination, ataxia, high stepping gait of forelimbs, bunny-hop movement of rear legs, or swaying of back end, but not including abnormalities involving only one leg or one front and one back leg; (ix) repeated intense rubbing with bare areas or damaged wool in similar locations on both sides of the animal’s body or, if on the head, both sides of the poll; (x) abraded, rough, thickened, or hyperpigmented areas of skin in areas of wool/hair loss in similar locations on both sides of the animal’s body or, if on the head, both sides of the poll; or (xi) other signs of CNS disease. An animal will no longer be a suspect animal if it is redesignated in accordance with §

 

79.4 of this chapter.

 

16. Add definition of tamper-resistant sampling kit and changes definition of Official genotype test to allow sampling using an APHIS approved tamper evident eartag for official genotyping. Note: APHIS is not aware of tamper-evident versions of these devices being commercially available.

 

17. Add definition of owner/hauler statement in place of previous owner statement.

 

Owner/hauler statement. A signed written statement by the owner or hauler that includes:

 

(1) The name, address, and phone number of the owner and, if different, the hauler;

 

(2) The date the animals were moved;

 

(3) The flock identification number or PIN assigned to the flock or premises of the animals;

 

(4) If moving individually unidentified animals, the group/lot identification number and any information required to officially identify the animals;

 

(5) The number of animals;

 

(6) The species, breed, and class of animals. If breed is unknown, for sheep the face color and for goats the type (milk, fiber, or meat) must be recorded instead; and

 

(7) The name and address of point of origin, if different from the owner’s address, and the destination.

 

18. Add definition:

 

Restricted animal sale or restricted livestock facility. A sale where any animals in slaughter channels are maintained separate from other animals not in slaughter channels and are sold in lots that consist entirely of animals sold for slaughter only or a livestock facility at which

 

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all animals are in slaughter channels and where the sale or facility manager maintains a copy of, or maintains a record of, the information from, the owner/hauler statement for all animals entering and leaving the sale or facility. A restricted animal sale may be held at a livestock facility that is not restricted.

 

19. Tighten up slaughter channels through revised definition and requirement for an owner hauler statement and addition of §79.3(g).

 

Slaughter channels. Animals in slaughter channels include any animal that is sold, transferred, or moved either directly to or through a restricted animal sale or restricted livestock facility to a slaughter establishment that is under continuous inspection by the Food Safety and Inspection Service or under State inspection that the Food Safety and Inspection Service has recognized as at least equal to Federal inspection or to a custom exempt slaughter establishment as defined by FSIS for immediate slaughter or to an individual for immediate slaughter for personal use or to a terminal feedlot. Any animal sold at an unrestricted sale is not in slaughter channels. Animals in slaughter channels must be accompanied by an owner/hauler statement completed in accordance with § 79.3(g) of this chapter. Animals in slaughter channels may not be held in the same enclosure with sexually intact animals from another flock of origin that are not in slaughter channels. When selling animals that do not meet the requirements to move as breeding animals, owners must note on the bill of sale that the animals are sold only for slaughter.

 

79.3(g) Animals moved to slaughter. Once an animal enters slaughter channels the animal may not be removed from slaughter channels. An animal is in slaughter channels if it was sold through a restricted animal sale, resided in a terminal feedlot, was sold with a bill of sale marked for slaughter only, was identified with an identification device or tattoo marked “slaughter only” or “MEAT” or was moved in a manner not permitted for other classes of animals. Animals in slaughter channels may move either directly to a slaughter establishment that is under continuous inspection by the Food Safety and Inspection Service or under State inspection that the Food Safety and Inspection Service has recognized as at least equal to Federal inspection or to a custom exempt slaughter establishment as defined by FSIS for immediate slaughter or to an individual for immediate slaughter for personal use, to a terminal feedlot, or may move indirectly to such a destination through a restricted animal sale or restricted livestock facility. Once an animal has entered slaughter channels it may only be officially identified with an official blue eartag marked with the words “Meat” or “Slaughter Only" or an ear tattoo reading "Meat." Animals in slaughter channels must be accompanied by an owner/hauler statement indicating the owner’s name and address; the name and address of the person or livestock facility from which and where they were acquired, if different from the owner; the slaughter establishment,

 

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restricted animal sale, restricted livestock facility or terminal feedlot to which they are being moved, and a statement that the animals are in slaughter channels. A copy of the owner/hauler statement must be provided to the slaughter establishment, restricted animal sale, restricted livestock facility or terminal feedlot to which the animals are moved. Any bill of sale regarding the animals must indicate that the animals were sold for slaughter only.

 

20. Revises Terminal feedlot definition by revising paragraph 1 to include removal of organic material before use by other sheep or goats, by adding paragraph 2, and revising paragraph 3 (now 4) to increase the record retention requirement to 5 years and reiterate that the owner hauler statement or the information contained therein must be retained: Terminal feedlot. (1) A dry lot approved by a State or APHIS representative or an accredited veterinarian who is authorized to perform this function where animals in the terminal feedlot are separated from all other animals by at least 30 feet at all times or are separated by a solid wall through, over, or under which fluids cannot pass and contact cannot occur and must be cleaned of all organic material prior to being used to contain sheep or goats that are not in slaughter channels, where only castrated males are maintained with female animals and from which animals are moved only to another terminal feedlot or directly to slaughter; or

 

(2) A dry lot approved by a State or APHIS representative or an accredited veterinarian authorized to perform this function where only animals that either are not pregnant based on the animal being male, an owner certification that any female animals have not been exposed to a male in the preceding 6 months, an ICVI issued by an accredited veterinarian stating the animals are open, or the animals are under 6 months of age at time of receipt, where only castrated males are maintained with female animals, and all animals in the terminal feedlot are separated from all other animals such that physical contact cannot occur and from which animals are moved only to another terminal feedlot or directly to slaughter; or

 

(3) A pasture when approved by and maintained under the supervision of the State and in which only nonpregnant animals are permitted based on the animal being male, an owner certification that any female animals have not been exposed to a male in the preceding 6 months, or an ICVI issued by an accredited veterinarian stating the animals are open, or the animals are under 6 months of age at time of receipt, where only castrated males are maintained with female animals, where there is no direct fence-to-fence contact with another flock, and from which animals are moved only to another terminal feedlot or directly to slaughter.

 

(4) Records of all animals entering and leaving a terminal feedlot must be maintained for 5 years after the animal leaves the feedlot and must meet the requirements of § 79.2 of this chapter,

 

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including either a copy of the required owner/hauler statements for animals entering and leaving the facility or the information required to be on the statements. Records must be made available for inspection and copying by an APHIS or State representative upon request.

 

21. In the indemnity sections proposed § 54.3 adds:

 

a. Prohibitions:

 

No indemnity will be paid for any animal, or the progeny of any animal, that has been moved or handled by the owner in violation of the requirements of the Animal Health Protection Act or the regulations promulgated thereunder. No indemnity will be paid for an animal added to the premises while a flock is under investigation or while it is an infected or source flock other than natural additions. No indemnity will be paid for natural additions born more than 60 days after the owner is notified they are eligible for indemnity unless the Administrator makes a determination that the dam could not be removed within the allowed time as a result of conditions outside the control of the owner. No indemnity will be paid unless the owner has signed and is in compliance with the requirements of a flock plan or PEMMP as described in § 54.8.

 

b. Allows partial indemnity if cleaning and disinfection cannot be completed due weather or other factors outside the control of the owner make immediate disinfection impractical.

 

c. Moves specific instructions for calculating indemnity to the program standards which includes specific language on late gestation and early lambing premiums as well as allows for the use of available price reports rather than specifying particular ones, which may become unavailable. See proposed § 54.6 and draft program standards for details.

 

22. Add language stating that APHIS may pay full disposal costs for indemnified animals

 

23. Add use of an EPA approved product should one be approved or new exempted products

 

24. Update section § 54.8 Requirements for flocks under investigation and flocks subject to flock plans and post-exposure management and monitoring plans (PEMMPs)

 

a. Reorganized and reworded for clarity

 

b. Adds flocks under investigation to the requirements for official identification

 

c. Requires official identification on all animals in a flock under a flock plan or PEMMP

 

d. Specifically allows APHIS to establish policies for retention of high-risk animals.

 

e. Gives more flexibility on when a PEMMP will be used

 

25. Update section § 54.10 Program approval of tests for scrapie

 

a. Adds information on appeals

 

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b. Moves test use guidelines to the APHIS website. See draft program standards for details.

 

26. Update section § 54.11 Approval of laboratories to run official scrapie tests and official genotype tests

 

a. Adds ability for NVSL to waive tissue retention times in an SOP

 

b. Adds additional information on appeals

 

c. Adds that NVSL may recoup costs associated with laboratory approval from the approved laboratories

 

27. Change low-risk commercial sheep to low-risk commercial flock to include goats, but limits this exception to animals moving for slaughter

 

28. Require submission of tagging records by individuals who tag animals for others such as markets and veterinarians through a website or by other mutually agreed methods.

 

29. Revise information required to be maintained about animal dispositions/acquisitions and records of animals tagged. Remove requirement to record tags that are on animals when acquired unless an ICVI is required.

 

30. Add meeting surveillance targets as a requirement for remaining a consistent state and requires States to conduct of facilitate surveillance in State inspected mature sheep and goat slaughter establishments (see proposed § 79.6).

 

31. Simplify the requirements for inconsistent states and includes the option to use genotyping for movement of breeding sheep in addition to enrollment in SFCP (see proposed § 79.3(j)).

 

32. Move the Consistent State List to the website in the program standards and provides for notice and comment for changing the list. Specifically, the definition is changed to read:

 

Consistent State. (1) A State that the Administrator has determined conducts an active State scrapie control program that meets the requirements of §79.6 or effectively enforces a State-designed plan that the Administrator determines is at least as effective in controlling scrapie as the requirements of § 79.6.

 

(2) A list of Consistent States can be found on the Internet at http://www.aphis.usda.gov/animal-health/scrapie.

 

(3) When the Administrator determines that a State should be added to or removed from the list of Consistent States, APHIS will publish a notice in the Federal Register advising the public of the Administrator's determination, providing the reasons for that determination, and soliciting public comments. After considering any comments we receive, APHIS will publish a second notice either advising the public that the Administrator has decided to add or remove the State from the list of Consistent States or notifying the public that the Administrator has decided not to make any changes to the list of Consistent States, depending on the information presented in the comments.

 

SCRAPIE

 

359

 

33. Add/revise definitions for flock identification (ID) number, Premises identification number (PIN) and group/lot number

 

Flock identification (ID) number. A nationally unique number assigned by a State or Federal animal health authority to a group of animals that are managed as a unit on one or more premises and are under the same ownership. The flock ID number must begin with the State postal abbreviation, must have no more than nine alphanumeric characters, and must not contain the characters “I”, “O”, or "Q" other than as part of the State postal abbreviation or another standardized format authorized by the administrator and issued through the National Scrapie Database. Flock identification numbers will be linked in the National Scrapie Database to one or more PINs and may be used in conjunction with an animal number unique within the flock to provide a unique official identification number for an animal, or may be used in conjunction with the date and a sequence number to provide a GIN for a group of animals when group identification is permitted.

 

Premises identification number (PIN). This term has the meaning set forth in § 86.1 of this subchapter. APHIS may also maintain historical and/or State premises numbers and link them to the premises identification number in records and databases. Such secondary or historical numbers are typically the State's two-letter postal abbreviation followed by a number assigned by the State.

 

Group/lot identification number (GIN). The identification number used to uniquely identify a unit of animals that is managed together as one group. The format of the GIN may be either as defined in § 71.1 of this chapter, or the flock identification number followed by a six-digit representation of the date on which the group or lot of animals was assembled (MM/DD/YY). If more than one group is created on the same date a sequential number will be added to the end of the GIN. If a flock identification number is used, the flock identification number, date, and sequential number will be separated by hyphens.

 

34. Revise definitions of Animal identification number (AIN), Officially identified, Official identification device or method and Official Eartag for clarity to specific the use of devices approved and distributed in accordance the scrapie rules and methods approved for use in sheep and goats by APHIS.

 

35. Explicitly allows an appeal of designation decisions see proposed § 79.4(c)(3). Draft rules of practice may be found in the draft program standards.

 

Prohibit transferring official eartags without the permission of APHIS or the State or applying official sheep and goat tags to animals other than sheep or goats. See proposed § 79.2 (b)(5)(d&e)

 

36. Does not allow use of back tags as official ID.

 

37. Provide for eartagging compliance agreements. See proposed § 79.3 (k).

 

REPORT OF THE COMMITTEE

 

360

 

38. Allow APHIS through the program standards or other web posting to establish the requirements for official identification devices and methods including:

 

a. Establishing allowed colors and limiting certain colors to certain uses. For example only “slaughter only” official sheep and goat eartags can be blue and all “slaughter only” official sheep and goat eartags must be blue. Specifies that yellow metal official tags will be used for permanently exposed animals and that red metal official tags will be used for animals that have tested positive for scrapie.

 

b. Requirements for use of tattoos. Proposed changes:

 

i. Not allowed as a sole means of official identification on animals in slaughter channels or moving through livestock markets

 

ii. Registry tattoos must be issued by a registry that has agreed to cooperate with APHIS in tracing scrapie positive and exposed animals or the registry tattoo prefix must be provide to APHIS for entry into the National Scrapie Database.

 

c. Requirements for use of electronic implants. Proposed changes:

 

i. Not allowed as a sole means of official identification on animals in slaughter channels or moving through livestock markets

 

ii. If used as the sole form of official identification must be tattooed with “E” for implants in the ear or “ET” for implants in the tail

 

iii. If used in an unregistered animal must also be tattooed with the flock identification number.

 

d. Specifies that eartags must be placed in the ear.

 

See the draft program standards (link) or the extract of materials (link) referred to in the proposed rule available on the web for more detailed information.

 

360

 

Specialist Commission Reports

 

A. Scientific Commission for Animal Diseases (SCAD) – The SCAD addresses technical issues, and makes science based recommendations to the Terrestrial Animal Health Standards (Code) Commission for improving and updating the various Code Chapters. The President of the SCAD summarized the activities of the Commission during the previous year. These included:

 

a. Overseeing and directing the work of 21 different expert ad hoc groups;

 

b. Amending and finalizing the chapters on:

 

 snip...

 

 Bovine spongiform encephalopathy (BSE), making a clear distinction between classical and atypical BSE, and clarifying that it is only the classical form for which status is granted, and that findings of atypical BSE do not affect status;

 

snip...

 

241

 

s. Bovine Spongiform Encephalopathy (Chapter 11.4) – this chapter was updated to recognize the distinction between “classical BSE” and “atypical BSE.” New Zealand, on behalf of the Quads countries (New Zealand, Australia, United States, and Canada), made an intervention. Specifically, the Quads are concerned that once again changes to a current Terrestrial Animal Health Code chapter are being proposed for adoption without Member Countries being given the appropriate opportunity to consider the changes carefully and offer comment to the Terrestrial Animal Health Standards Commission. While acknowledging that there may be occasions when changes to Code chapters must be made with urgency, this was not such an occasion. The Quads recognized the need to make a distinction between the occurrence of a case of “classical” BSE and a case of “atypical” BSE, and welcomed the recognition that a case of “atypical” BSE, an uncommon, spontaneously occurring condition, should not negatively affect a country’s BSE risk status. However, the changes proposed have broader implications. With the normal cycle of Member Country comments on proposed changes, countries would have time to recognise the implications for surveillance and information gathering systems and be prepared when the changes are adopted after the normal process of consultation and comment. The Quads also pointed to another problem with rushing this revised text through. A very important distinction is made between “classical” and “atypical” BSE. However, nowhere in the Code or Manual is there a case definition for either condition. Before the Code recommends different responses to these two conditions, the OIE Member Countries should be provided with definitive case

 

REPORT OF THE COMMITTEE

 

246

 

definitions so as to avoid ambiguity and dispute over BSE status. Since the occurrence of “atypical” BSE has been recognised for several years now, the Quads suggested that there was no need for urgency to make changes to the Code and the normal cycle of Member Countries’ scrutiny, comment and consultation should be followed. The EU, however, did have an urgency to get these changes through (likely because they have been detecting “atypical” cases of BSE and did not want these to influence their status, since the Code does not currently make such a distinction). A compromise was reached by not adopting the proposed changes, but adding a short sentence at the end of the introductory paragraph of the chapter which reads: “For the purpose of official BSE status recognition, BSE excludes ‘atypical BSE’ as it is a condition believed to occur spontaneously in all cattle populations at a very low rate.” Countries can now review the proposed changes and submit any comments before the next meeting of the Code Commission in September 2015.

 

246

 

http://www.usaha.org/Portals/6/Proceedings/2015%20Proceedings%20web2.pdf

 

PRION 2016 CONFERENCE TOKYO

 

SCRAPIE WS-01: Prion diseases in animals and zoonotic potential 2016

 

 Prion. 10:S15-S21. 2016 ISSN: 1933-6896 printl 1933-690X online

 

 Taylor & Francis

 

 Prion 2016 Animal Prion Disease Workshop Abstracts

 

 WS-01: Prion diseases in animals and zoonotic potential

 

 Juan Maria Torres a, Olivier Andreoletti b, J uan-Carlos Espinosa a. Vincent Beringue c. Patricia Aguilar a,

 

 Natalia Fernandez-Borges a. and Alba Marin-Moreno a

 

 "Centro de Investigacion en Sanidad Animal ( CISA-INIA ). Valdeolmos, Madrid. Spain; b UMR INRA -ENVT 1225 Interactions Holes Agents Pathogenes. ENVT. Toulouse. France: "UR892. Virologie lmmunologie MolécuIaires, Jouy-en-Josas. France

 

 Dietary exposure to bovine spongiform encephalopathy (BSE) contaminated bovine tissues is considered as the origin of variant Creutzfeldt Jakob (vCJD) disease in human. To date, BSE agent is the only recognized zoonotic prion. Despite the variety of Transmissible Spongiform Encephalopathy (TSE) agents that have been circulating for centuries in farmed ruminants there is no apparent epidemiological link between exposure to ruminant products and the occurrence of other form of TSE in human like sporadic Creutzfeldt Jakob Disease (sCJD). However, the zoonotic potential of the diversity of circulating TSE agents has never been systematically assessed. The major issue in experimental assessment of TSEs zoonotic potential lies in the modeling of the ‘species barrier‘, the biological phenomenon that limits TSE agents’ propagation from a species to another. In the last decade, mice genetically engineered to express normal forms of the human prion protein has proved essential in studying human prions pathogenesis and modeling the capacity of TSEs to cross the human species barrier.

 

 To assess the zoonotic potential of prions circulating in farmed ruminants, we study their transmission ability in transgenic mice expressing human PrPC (HuPrP-Tg). Two lines of mice expressing different forms of the human PrPC (129Met or 129Val) are used to determine the role of the Met129Val dimorphism in susceptibility/resistance to the different agents.

 

 These transmission experiments confirm the ability of BSE prions to propagate in 129M- HuPrP-Tg mice and demonstrate that Met129 homozygotes may be susceptible to BSE in sheep or goat to a greater degree than the BSE agent in cattle and that these agents can convey molecular properties and neuropathological indistinguishable from vCJD. However homozygous 129V mice are resistant to all tested BSE derived prions independently of the originating species suggesting a higher transmission barrier for 129V-PrP variant.

 

 Transmission data also revealed that several scrapie prions propagate in HuPrP-Tg mice with efficiency comparable to that of cattle BSE. While the efficiency of transmission at primary passage was low, subsequent passages resulted in a highly virulent prion disease in both Met129 and Val129 mice. Transmission of the different scrapie isolates in these mice leads to the emergence of prion strain phenotypes that showed similar characteristics to those displayed by MM1 or VV2 sCJD prion. These results demonstrate that scrapie prions have a zoonotic potential and raise new questions about the possible link between animal and human prions.

 

http://www.tandfonline.com/na101/home/literatum/publisher/tandf/journals/content/kprn20/2016/kprn20.v010.sup01/19336896.2016.1163048/20160418/19336896.2016.1163048.fp.png_v03

 

http://www.tandfonline.com/doi/abs/10.1080/19336896.2016.1163048?journalCode=kprn20

 

*** Transmission data also revealed that several scrapie prions propagate in HuPrP-Tg mice with efficiency comparable to that of cattle BSE. While the efficiency of transmission at primary passage was low, subsequent passages resulted in a highly virulent prion disease in both Met129 and Val129 mice. Transmission of the different scrapie isolates in these mice leads to the emergence of prion strain phenotypes that showed similar characteristics to those displayed by MM1 or VV2 sCJD prion. These results demonstrate that scrapie prions have a zoonotic potential and raise new questions about the possible link between animal and human prions.

 

http://www.tandfonline.com/doi/abs/10.1080/19336896.2016.1163048?journalCode=kprn20

 

Research Project: TRANSMISSION, DIFFERENTIATION, AND PATHOBIOLOGY OF TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES

 

Title: Transmission of scrapie prions to primate after an extended silent incubation period

 

Authors

 

item Comoy, Emmanuel - item Mikol, Jacqueline - item Luccantoni-Freire, Sophie - item Correia, Evelyne - item Lescoutra-Etchegaray, Nathalie - item Durand, Valérie - item Dehen, Capucine - item Andreoletti, Olivier - item Casalone, Cristina - item Richt, Juergen item Greenlee, Justin item Baron, Thierry - item Benestad, Sylvie - item Hills, Bob - item Brown, Paul - item Deslys, Jean-Philippe -

 

Submitted to: Scientific Reports Publication Type: Peer Reviewed Journal Publication Acceptance Date: May 28, 2015 Publication Date: June 30, 2015 Citation: Comoy, E.E., Mikol, J., Luccantoni-Freire, S., Correia, E., Lescoutra-Etchegaray, N., Durand, V., Dehen, C., Andreoletti, O., Casalone, C., Richt, J.A., Greenlee, J.J., Baron, T., Benestad, S., Brown, P., Deslys, J. 2015. Transmission of scrapie prions to primate after an extended silent incubation period. Scientific Reports. 5:11573.

 

Interpretive Summary: The transmissible spongiform encephalopathies (also called prion diseases) are fatal neurodegenerative diseases that affect animals and humans. The agent of prion diseases is a misfolded form of the prion protein that is resistant to breakdown by the host cells. Since all mammals express prion protein on the surface of various cells such as neurons, all mammals are, in theory, capable of replicating prion diseases. One example of a prion disease, bovine spongiform encephalopathy (BSE; also called mad cow disease), has been shown to infect cattle, sheep, exotic undulates, cats, non-human primates, and humans when the new host is exposed to feeds or foods contaminated with the disease agent. The purpose of this study was to test whether non-human primates (cynomologous macaque) are susceptible to the agent of sheep scrapie. After an incubation period of approximately 10 years a macaque developed progressive clinical signs suggestive of neurologic disease. Upon postmortem examination and microscopic examination of tissues, there was a widespread distribution of lesions consistent with a transmissible spongiform encephalopathy. This information will have a scientific impact since it is the first study that demonstrates the transmission of scrapie to a non-human primate with a close genetic relationship to humans. This information is especially useful to regulatory officials and those involved with risk assessment of the potential transmission of animal prion diseases to humans. Technical Abstract: Classical bovine spongiform encephalopathy (c-BSE) is an animal prion disease that also causes variant Creutzfeldt-Jakob disease in humans. Over the past decades, c-BSE's zoonotic potential has been the driving force in establishing extensive protective measures for animal and human health.

 

*** In complement to the recent demonstration that humanized mice are susceptible to scrapie, we report here the first observation of direct transmission of a natural classical scrapie isolate to a macaque after a 10-year incubation period. Neuropathologic examination revealed all of the features of a prion disease: spongiform change, neuronal loss, and accumulation of PrPres throughout the CNS.

 

*** This observation strengthens the questioning of the harmlessness of scrapie to humans, at a time when protective measures for human and animal health are being dismantled and reduced as c-BSE is considered controlled and being eradicated.

 

*** Our results underscore the importance of precautionary and protective measures and the necessity for long-term experimental transmission studies to assess the zoonotic potential of other animal prion strains.

 

http://www.ars.usda.gov/research/publications/publications.htm?SEQ_NO_115=313160

 

Transmission of scrapie prions to primate after an extended silent incubation period

 

Emmanuel E. Comoy , Jacqueline Mikol , Sophie Luccantoni-Freire , Evelyne Correia , Nathalie Lescoutra-Etchegaray , Valérie Durand , Capucine Dehen , Olivier Andreoletti , Cristina Casalone , Juergen A. Richt , Justin J. Greenlee , Thierry Baron , Sylvie L. Benestad , Paul Brown & Jean-Philippe Deslys

 

Scientific Reports 5, Article number: 11573 (2015) doi:10.1038/srep11573 Download Citation Epidemiology Neurological manifestations Prion diseases

 

Received:16 February 2015Accepted:28 May 2015

 

***Moreover, sporadic disease has never been observed in breeding colonies or primate research laboratories, most notably among hundreds of animals over several decades of study at the National Institutes of Health25, and in nearly twenty older animals continuously housed in our own facility.***

 

http://www.nature.com/articles/srep11573

 

Tuesday, December 16, 2014

 

Evidence for zoonotic potential of ovine scrapie prions

 

 Hervé Cassard,1, n1 Juan-Maria Torres,2, n1 Caroline Lacroux,1, Jean-Yves Douet,1, Sylvie L. Benestad,3, Frédéric Lantier,4, Séverine Lugan,1, Isabelle Lantier,4, Pierrette Costes,1, Naima Aron,1, Fabienne Reine,5, Laetitia Herzog,5, Juan-Carlos Espinosa,2, Vincent Beringue5, & Olivier Andréoletti1, Affiliations Contributions Corresponding author Journal name: Nature Communications Volume: 5, Article number: 5821 DOI: doi:10.1038/ncomms6821 Received 07 August 2014 Accepted 10 November 2014 Published 16 December 2014 Article tools Citation Reprints Rights & permissions Article metrics

 

 Abstract

 

 Although Bovine Spongiform Encephalopathy (BSE) is the cause of variant Creutzfeldt Jakob disease (vCJD) in humans, the zoonotic potential of scrapie prions remains unknown. Mice genetically engineered to overexpress the human ​prion protein (tgHu) have emerged as highly relevant models for gauging the capacity of prions to transmit to humans. These models can propagate human prions without any apparent transmission barrier and have been used used to confirm the zoonotic ability of BSE. Here we show that a panel of sheep scrapie prions transmit to several tgHu mice models with an efficiency comparable to that of cattle BSE. The serial transmission of different scrapie isolates in these mice led to the propagation of prions that are phenotypically identical to those causing sporadic CJD (sCJD) in humans. These results demonstrate that scrapie prions have a zoonotic potential and raise new questions about the possible link between animal and human prions.

 

 snip...

 

 Do our transmission results in tgHu imply that sheep scrapie is the cause of sCJD cases in humans? This question challenges well-established dogma that sCJD is a spontaneous disorder unrelated to animal prion disease. In our opinion, our data on their own do not unequivocally establish a causative link between natural exposure to sheep scrapie and the subsequent appearance of sCJD in humans. However, our studies clearly point out the need to re-consider this possibility. Clarification on this topic will be aided by informed and modern epidemiological studies to up-date previous analysis that was performed at the end of the last century3, 4. The value of such an approach is highlighted by the implementation in the year 2000 of large-scale active animal TSE surveillance programs around the world that provided an informed epidemiological-based view of the occurrence and geographical spread of prion disease in small ruminant populations51. The fact that both Australia and New-Zealand, two countries that had been considered for more than 50 years as TSE-free territories, were finally identified positive for atypical scrapie in their sheep flocks provides an example of how prion dogma can be reversed52. However, the incubation period for prion disease in humans after exposure to prions via the peripheral route, such as in iatrogenic CJD transmission and Kuru, can exceed several decades53, 54. In this context, it will be a challenge to combine epidemiological data collected contemporarily in animal populations and humans to investigate the existence of a causative link between prion disease occurrence in these different hosts. Furthermore, it is crucial to bear in mind that sporadic sCJD in humans is a rare disease (1–2 individuals per million of the population per year) and that scrapie has been circulating in small ruminants populations used for food purposes for centuries. Consequently, it is our opinion that even if a causative link was established between sheep scrapie exposure and the occurrence of certain sCJD cases, it would be wrong to consider small ruminant TSE agents as a new major threat for public health. Despite this, it remains clear that our data provide a new impetus to establish the true zoonotic potential of sheep scrapie prions.

 

Subject terms: Biological sciences• Medical research At a glance

 

http://www.nature.com/ncomms/2014/141216/ncomms6821/full/ncomms6821.html

 

Thursday, August 04, 2016

 

MEETING ON THE FEASIBILITY OF CARRYING OUT EPIDEMIOLOGICAL STUDIES ON CREUTZFELDT JAKOB DISEASE 1978 THE SCRAPIE FILES IN CONFIDENCE CONFIDENTIAL SCJD

 

http://scrapie-usa.blogspot.com/2016/08/meeting-on-feasibility-of-carrying-out.html

 

SEE CONFIDENTIAL SCRAPIE FILES ;

 

http://collections.europarchive.org/tna/20090505194948/http://bseinquiry.gov.uk/files/yb/1978/03/09001001.pdf

 

http://collections.europarchive.org/tna/20090505194948/http://bseinquiry.gov.uk/files/yb/1978/06/01001001.pdf

 

http://collections.europarchive.org/tna/20090505194948/http://bseinquiry.gov.uk/files/yb/1978/06/27001001.pdf

 

BE SURE TO SEE THIS NEXT ONE WITH FIGURES...TSS

 

STUDIES ON CREUTZFELDT-JAKOB DISEASE

 

i enclose a list of ICD categories showing the numbers of deaths attributed to each (as underlying cause) in England and Hales in 1975.

 

ICD NO...Number of Certificates examined

 

xxxxx...18...15 mentioned C-J

 

xxxxx...122...1 mentioned C-J with dimentia, 24 mentioned Alzheimer’s disease, 1 mentioned Pick’s disease.

 

xxxxx...22...4 mentioned Myoclonic epilepsy

 

xxxxx...384...none mentioned Corticostrionigral degeneration

 

xxxxx...2...none mentioned Corticostrionigral degeneration

 

snip...

 

http://collections.europarchive.org/tna/20090505194948/http://bseinquiry.gov.uk/files/yb/1978/06/27002001.pdf

 

http://collections.europarchive.org/tna/20090505194948/http://bseinquiry.gov.uk/files/yb/1978/06/27003001.pdf

 

http://collections.europarchive.org/tna/20090505194948/http://bseinquiry.gov.uk/files/yb/1978/06/27004001.pdf

 

http://collections.europarchive.org/tna/20090505194948/http://bseinquiry.gov.uk/files/yb/1978/08/18001001.pdf

 

http://collections.europarchive.org/tna/20090505194948/http://bseinquiry.gov.uk/files/yb/1978/10/06001001.pdf

 

http://collections.europarchive.org/tna/20090505194948/http://bseinquiry.gov.uk/files/yb/1978/10/06002001.pdf

 

1979

 

SILENCE ON CJD AND SCRAPIE

 

1980

 

SILENCE ON CJD AND SCRAPIE

 

*** 1981 NOVEMBER

 

http://collections.europarchive.org/tna/20090505194948/http://bseinquiry.gov.uk/files/yb/1981/11/26001001.pdf

 

http://collections.europarchive.org/tna/20090505194948/http://bseinquiry.gov.uk/files/yb/1981/11/26001001.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

 

 *** 1976 Scrapie Research USDA worried about Scrapie and sCJD in man...tss

 

http://collections.europarchive.org/tna/20090505194948/http://bseinquiry.gov.uk/files/yb/1976/10/12002001.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

 

 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

 

 why do we not want to do TSE transmission studies on chimpanzees $

 

 IN CONFIDENCE

 

 TRANSMISSION TO CHIMPANZEES

 

 snip...

 

 5. A positive result from a chimpanzee challenged severely would likely create alarm in some circles even if the result could not be interpreted for man. I have a view that all these agents could be transmitted provided a large enough dose by appropriate routes was given and the animals kept long enough. Until the mechanisms of the species barrier are more clearly understood it might be best to retain that hypothesis.

 

 snip...

 

 R. BRADLEY

 

 http://collections.europarchive.org/tna/20080102222950/http://www.bseinquiry.gov.uk/files/yb/1990/09/23001001.pdf

 

 full text ;

 

 RB3.20

 

 IN CONFIDENCE

 

 TRANSMISSION TO CHIMPANZEE

 

 1. Kuru and CJD have been successfully transmitted to chimpanzees but scrapie and TME have not.

 

 2. We cannot say that scrapie will not transmit to chimpanzees. There are several scrapie strains and I am not aware that all have been tried (that would have to be from mouse passaged material). Nor has a wide enough range of field isolates subsequently strain typed in mice been inoculated by the appropriate routes (i/c, i/p and i v);

 

 3. I believe the proposed experiment to determine transmissibility, if conducted, would only show the susceptibility or resistance of the chimpanzee to infection/disease by the routes used and the result could not be interpreted for the predictability of the susceptibility for man. Proposals for prolonged oral exposure of chimpanzees to milk from cattle were suggested a long while ago and rejected.

 

 4. In view of Dr Gibbs‘ probable use of Chimpazees Mr Wells‘ comments (enclosed) are pertinent. I have yet to receive a direct communication from Dr Schellekers but before any collaboration or provision of material we should identify the Gibbs' proposals and objectives.

 

 5. A positive result from a chimpanzee challenged severely would likely create alarm in some circles even if the result could not be interpreted for man. I have a view that all these agents could be transmitted provided a large enough dose by appropriate routes was given and the animals kept long enough. Until the mechanisms of the species barrier are more clearly understood it might be best to retain that hypothesis.

 

 A negative result would take a lifetime to determine but that would be a shorter period than might be available for human exposure and it would still not answer the question regarding mans' susceptibility. In the meantime no doubt the negativity would be used defensively. It would however be counterproductive if the experiment finally became positive- We may learn more about public reactions following next Monday‘s meeting. CVO (+ Mr. Wells’ comments)

 

 Dr. T W A Little

 

 Dr. B J Shreeve

 

 R Bradley September 1990

 

 90/9.23/1/1

 

 http://collections.europarchive.org/tna/20080102222950/http://www.bseinquiry.gov.uk/files/yb/1990/09/23001001.pdf

 

Saturday, April 23, 2016

 

SCRAPIE WS-01: Prion diseases in animals and zoonotic potential 2016 TOKYO

 

Prion. 10:S15-S21. 2016 ISSN: 1933-6896 printl 1933-690X

 

http://scrapie-usa.blogspot.com/2016/04/scrapie-ws-01-prion-diseases-in-animals.html

 

Tuesday, June 07, 2016

 

*** Comparison of two US sheep scrapie isolates supports identification as separate strains ***

 

Research Project: TRANSMISSION, DIFFERENTIATION, AND PATHOBIOLOGY OF TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES

 

http://scrapie-usa.blogspot.com/2016/06/comparison-of-two-us-sheep-scrapie.html

 

THIS IS most important as well, and you may not be aware of this, if not, you and your colleagues should please take note ‘After a natural route of exposure, 100% of white-tailed deer were susceptible to scrapie’, and below this as well, I am now beginning to question the Red Deer Ataxia back in the 70s and 80s, as I did the infamous ‘hound ataxia’.

 

*** After a natural route of exposure, 100% of white-tailed deer were susceptible to scrapie. ***

 

2011

 

*** After a natural route of exposure, 100% of white-tailed deer were susceptible to scrapie. ***

 

http://www.usaha.org/Portals/6/Reports/2011/report-cwal-2011.pdf

 

Primary transmission of CWD versus scrapie prions from small ruminants to ovine and cervid PrP transgenic mice

 

Authors: Sally A. Madsen-Bouterse1, David A. Schneider2, Dongyue Zhuang3, Rohana P. Dassanayake4, Aru Balachandran5, Gordon B. Mitchell6, Katherine I. O'Rourke7  VIEW AFFILIATIONS

 

Published Ahead of Print: 08 July, 2016 Journal of General Virology doi: 10.1099/jgv.0.000539 Published Online: 08/07/2016

 

Development of mice expressing either ovine (Tg338) or cervid (TgElk) prion protein (PrP) have aided in characterization of scrapie and chronic wasting disease (CWD), respectively. Experimental inoculation of sheep with CWD prions has demonstrated the potential for interspecies transmission but, infection with CWD versus classical scrapie prions may be difficult to differentiate using validated diagnostic platforms. In this study, mouse bioassay in Tg338 and TgElk was utilized to evaluate transmission of CWD versus scrapie prions from small ruminants. Mice (>5/homogenate) were inoculated with brain homogenates from clinically affected sheep or goats with naturally-acquired classical scrapie, white-tailed deer with naturally-acquired CWD (WTD-CWD), or sheep with experimentally-acquired CWD derived from elk (sheep-passaged-CWD). Survival time (time to clinical disease) and attack rates (brain accumulation of protease resistant PrP, PrPres) were determined. Inoculation with classical scrapie prions resulted in clinical disease and 100% attack rates in Tg338, but no clinical disease at endpoint (>300 days post inoculation, dpi) and low attack rates (6.8%) in TgElk. Inoculation with WTD-CWD prions yielded no clinical disease or brain PrPres accumulation in Tg338 at endpoint (>500dpi) but rapid onset of clinical disease (~121dpi) and 100% attack rate in TgElk. Sheep-passaged-CWD resulted in transmission to both mouse lines with 100% attack rates at endpoint in Tg338 and an attack rate of ~73% in TgElk with some culled due to clinical disease. These primary transmission observations demonstrate the potential of bioassay in Tg338 and TgElk to help differentiate possible infection with CWD versus classical scrapie prions in sheep and goats.

 

http://jgv.microbiologyresearch.org/content/journal/jgv/10.1099/jgv.0.000539

 

P.97: Scrapie transmits to white-tailed deer by the oral route and has a molecular profile similar to chronic wasting disease and distinct from the scrapie inoculum

 

Justin Greenlee1, S Jo Moore1, Jodi Smith1, M Heather West Greenlee2, and Robert Kunkle1

 

1National Animal Disease Center; Ames, IA USA;

 

2Iowa State University; Ames, IA USA

 

The purpose of this work was to determine susceptibility of white-tailed deer (WTD) to the agent of sheep scrapie and to compare the resultant PrPSc to that of the original inoculum and chronic wasting disease (CWD). We inoculated WTD by a natural route of exposure (concurrent oral and intranasal (IN); n D 5) with a US scrapie isolate. All scrapie-inoculated deer had evidence of PrPSc accumulation. PrPSc was detected in lymphoid tissues at preclinical time points, and deer necropsied after 28 months post-inoculation had clinical signs, spongiform encephalopathy, and widespread distribution of PrPSc in neural and lymphoid tissues. Western blotting (WB) revealed PrPSc with 2 distinct molecular profiles. WB on cerebral cortex had a profile similar to the original scrapie inoculum, whereas WB of brainstem, cerebellum, or lymph nodes revealed PrPSc with a higher profile resembling CWD. Homogenates with the 2 distinct profiles from WTD with clinical scrapie were further passaged to mice expressing cervid prion protein and intranasally to sheep and WTD. In cervidized mice, the 2 inocula have distinct incubation times. Sheep inoculated intranasally with WTD derived scrapie developed disease, but only after inoculation with the inoculum that had a scrapie-like profile. The WTD study is ongoing, but deer in both inoculation groups are positive for PrPSc by rectal mucosal biopsy. In summary, this work demonstrates that WTD are susceptible to the agent of scrapie, 2 distinct molecular profiles of PrPSc are present in the tissues of affected deer, and inoculum of either profile readily passes to deer.

 

https://prion2015.files.wordpress.com/2015/05/prion2015abstracts.pdf

 

2012

 

PO-039: A comparison of scrapie and chronic wasting disease in white-tailed deer

 

Justin Greenlee, Jodi Smith, Eric Nicholson US Dept. Agriculture; Agricultural Research Service, National Animal Disease Center; Ames, IA USA

 

snip...

 

The results of this study suggest that there are many similarities in the manifestation of CWD and scrapie in WTD after IC inoculation including early and widespread presence of PrPSc in lymphoid tissues, clinical signs of depression and weight loss progressing to wasting, and an incubation time of 21-23 months. Moreover, western blots (WB) done on brain material from the obex region have a molecular profile similar to CWD and distinct from tissues of the cerebrum or the scrapie inoculum. However, results of microscopic and IHC examination indicate that there are differences between the lesions expected in CWD and those that occur in deer with scrapie: amyloid plaques were not noted in any sections of brain examined from these deer and the pattern of immunoreactivity by IHC was diffuse rather than plaque-like.

 

*** After a natural route of exposure, 100% of WTD were susceptible to scrapie.

 

Deer developed clinical signs of wasting and mental depression and were necropsied from 28 to 33 months PI. Tissues from these deer were positive for PrPSc by IHC and WB. Similar to IC inoculated deer, samples from these deer exhibited two different molecular profiles: samples from obex resembled CWD whereas those from cerebrum were similar to the original scrapie inoculum. On further examination by WB using a panel of antibodies, the tissues from deer with scrapie exhibit properties differing from tissues either from sheep with scrapie or WTD with CWD. Samples from WTD with CWD or sheep with scrapie are strongly immunoreactive when probed with mAb P4, however, samples from WTD with scrapie are only weakly immunoreactive. In contrast, when probed with mAb’s 6H4 or SAF 84, samples from sheep with scrapie and WTD with CWD are weakly immunoreactive and samples from WTD with scrapie are strongly positive. This work demonstrates that WTD are highly susceptible to sheep scrapie, but on first passage, scrapie in WTD is differentiable from CWD.

 

http://www.landesbioscience.com/journals/prion/03-Prion6-2-Transmission-and-strains.pdf

 

Scrapie in Deer: Comparisons and Contrasts to Chronic Wasting Disease (CWD)

 

Justin J. Greenlee of the Virus and Prion Diseases Research Unit, National Animal Disease Center, ARS, USDA, Ames, IA provided a presentation on scrapie and CWD in inoculated deer. Interspecies transmission studies afford the opportunity to better understand the potential host range and origins of prion diseases. We inoculated white-tailed deer intracranially (IC) and by a natural route of exposure (concurrent oral and intranasal inoculation) with a US scrapie isolate. All deer inoculated by the intracranial route had evidence of PrPSc accumulation and those necropsied after 20 months post-inoculation (PI) (3/5) had clinical signs, spongiform encephalopathy, and widespread distribution of PrPSc in neural and lymphoid tissues. A single deer that was necropsied at 15.6 months PI did not have clinical signs, but had widespread distribution of PrPSc. This highlights the facts that 1) prior to the onset of clinical signs PrPSc is widely distributed in the CNS and lymphoid tissues and 2) currently used diagnostic methods are sufficient to detect PrPSc prior to the onset of clinical signs. The results of this study suggest that there are many similarities in the manifestation of CWD and scrapie in white-tailed deer after IC inoculation including early and widespread presence of PrPSc in lymphoid tissues, clinical signs of depression and weight loss progressing to wasting, and an incubation time of 21-23 months. Moreover, western blots (WB) done on brain material from the obex region have a molecular profile consistent with CWD and distinct from tissues of the cerebrum or the scrapie inoculum. However, results of microscopic and IHC examination indicate that there are differences between the lesions expected in CWD and those that occur in deer with scrapie: amyloid plaques were not noted in any sections of brain examined from these deer and the pattern of immunoreactivity by IHC was diffuse rather than plaque-like. After a natural route of exposure, 100% of white-tailed deer were susceptible to scrapie. Deer developed clinical signs of wasting and mental depression and were necropsied from 28 to 33 months PI. Tissues from these deer were positive for scrapie by IHC and WB. Tissues with PrPSc immunoreactivity included brain, tonsil, retropharyngeal and mesenteric lymph nodes, hemal node, Peyer’s patches, and spleen. While two WB patterns have been detected in brain regions of deer inoculated by the natural route, unlike the IC inoculated deer, the pattern similar to the scrapie inoculum predominates.

 

http://www.usaha.org/Portals/6/Reports/2011/report-cwal-2011.pdf

 

White-tailed Deer are Susceptible to Scrapie by Natural Route of Infection

 

Jodi D. Smith, Justin J. Greenlee, and Robert A. Kunkle; Virus and Prion Research Unit, National Animal Disease Center, USDA-ARS

 

Interspecies transmission studies afford the opportunity to better understand the potential host range and origins of prion diseases. Previous experiments demonstrated that white-tailed deer are susceptible to sheep-derived scrapie by intracranial inoculation. The purpose of this study was to determine susceptibility of white-tailed deer to scrapie after a natural route of exposure. Deer (n=5) were inoculated by concurrent oral (30 ml) and intranasal (1 ml) instillation of a 10% (wt/vol) brain homogenate derived from a sheep clinically affected with scrapie. Non-inoculated deer were maintained as negative controls. All deer were observed daily for clinical signs. Deer were euthanized and necropsied when neurologic disease was evident, and tissues were examined for abnormal prion protein (PrPSc) by immunohistochemistry (IHC) and western blot (WB). One animal was euthanized 15 months post-inoculation (MPI) due to an injury. At that time, examination of obex and lymphoid tissues by IHC was positive, but WB of obex and colliculus were negative. Remaining deer developed clinical signs of wasting and mental depression and were necropsied from 28 to 33 MPI. Tissues from these deer were positive for scrapie by IHC and WB. Tissues with PrPSc immunoreactivity included brain, tonsil, retropharyngeal and mesenteric lymph nodes, hemal node, Peyer’s patches, and spleen. This work demonstrates for the first time that white-tailed deer are susceptible to sheep scrapie by potential natural routes of inoculation. In-depth analysis of tissues will be done to determine similarities between scrapie in deer after intracranial and oral/intranasal inoculation and chronic wasting disease resulting from similar routes of inoculation.

 

see full text ;

 

http://www.usaha.org/Portals/6/Reports/2010/report-cwal-2010.pdf

 

 *** How Did CWD Get Way Down In Medina County, Texas?

 

DISCUSSION Observations of natural outbreaks of scrapie indicated that the disease spread from flock to flock by the movement of infected, but apparently normal, sheep which were incubating the disease.

 

There was no evidence that the disease spread to adjacent flocks in the absent of such movements or that vectors or other host species were involved in the spread of scrapie to sheep or goats; however, these possibilities should be kept open...

 

http://web.archive.org/web/20030513212324/http://www.bseinquiry.gov.uk/files/mb/m08b/tab64.pdf

 

http://scrapie-usa.blogspot.com/2016/06/scrapie-field-trial-experiments-mission.html

 

http://chronic-wasting-disease.blogspot.com/2016/06/how-did-cwd-get-way-down-in-medina.html

 

*** Infectious agent of sheep scrapie may persist in the environment for at least 16 years ***

 

Gudmundur Georgsson1, Sigurdur Sigurdarson2 and Paul Brown3

 

http://jgv.sgmjournals.org/content/87/12/3737.full

 

Saturday, May 28, 2016

 

*** Infection and detection of PrPCWD in soil from CWD infected farm in Korea Prion 2016 Tokyo ***

 

http://chronic-wasting-disease.blogspot.com/2016/05/infection-and-detection-of-prpcwd-in.html

 

Monday, May 02, 2016

 

*** Zoonotic Potential of CWD Prions: An Update Prion 2016 Tokyo ***

 

http://chronic-wasting-disease.blogspot.com/2016/05/zoonotic-potential-of-cwd-prions-update.html

 

 2015

 

O.05: Transmission of prions to primates after extended silent incubation periods: Implications for BSE and scrapie risk assessment in human populations

 

Emmanuel Comoy, Jacqueline Mikol, Valerie Durand, Sophie Luccantoni, Evelyne Correia, Nathalie Lescoutra, Capucine Dehen, and Jean-Philippe Deslys Atomic Energy Commission; Fontenay-aux-Roses, France

 

Prion diseases (PD) are the unique neurodegenerative proteinopathies reputed to be transmissible under field conditions since decades. The transmission of Bovine Spongiform Encephalopathy (BSE) to humans evidenced that an animal PD might be zoonotic under appropriate conditions. Contrarily, in the absence of obvious (epidemiological or experimental) elements supporting a transmission or genetic predispositions, PD, like the other proteinopathies, are reputed to occur spontaneously (atpical animal prion strains, sporadic CJD summing 80% of human prion cases). Non-human primate models provided the first evidences supporting the transmissibiity of human prion strains and the zoonotic potential of BSE. Among them, cynomolgus macaques brought major information for BSE risk assessment for human health (Chen, 2014), according to their phylogenetic proximity to humans and extended lifetime. We used this model to assess the zoonotic potential of other animal PD from bovine, ovine and cervid origins even after very long silent incubation periods.

 

*** We recently observed the direct transmission of a natural classical scrapie isolate to macaque after a 10-year silent incubation period,

 

***with features similar to some reported for human cases of sporadic CJD, albeit requiring fourfold long incubation than BSE. Scrapie, as recently evoked in humanized mice (Cassard, 2014),

 

***is the third potentially zoonotic PD (with BSE and L-type BSE),

 

***thus questioning the origin of human sporadic cases. We will present an updated panorama of our different transmission studies and discuss the implications of such extended incubation periods on risk assessment of animal PD for human health.

 

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

 

***thus questioning the origin of human sporadic cases***

 

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

 

***our findings suggest that possible transmission risk of H-type BSE to sheep and human. Bioassay will be required to determine whether the PMCA products are infectious to these animals.

 

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

 

https://prion2015.files.wordpress.com/2015/05/prion2015abstracts.pdf

 

 PRION 2016 TOKYO

 

Zoonotic Potential of CWD Prions: An Update

 

Ignazio Cali1, Liuting Qing1, Jue Yuan1, Shenghai Huang2, Diane Kofskey1,3, Nicholas Maurer1, Debbie McKenzie4, Jiri Safar1,3,5, Wenquan Zou1,3,5,6, Pierluigi Gambetti1, Qingzhong Kong1,5,6

 

1Department of Pathology, 3National Prion Disease Pathology Surveillance Center, 5Department of Neurology, 6National Center for Regenerative Medicine, Case Western Reserve University, Cleveland, OH 44106, USA.

 

4Department of Biological Sciences and Center for Prions and Protein Folding Diseases, University of Alberta, Edmonton, Alberta, Canada,

 

2Encore Health Resources, 1331 Lamar St, Houston, TX 77010

 

Chronic wasting disease (CWD) is a widespread and highly transmissible prion disease in free-ranging and captive cervid species in North America. The zoonotic potential of CWD prions is a serious public health concern, but the susceptibility of human CNS and peripheral organs to CWD prions remains largely unresolved. We reported earlier that peripheral and CNS infections were detected in transgenic mice expressing human PrP129M or PrP129V. Here we will present an update on this project, including evidence for strain dependence and influence of cervid PrP polymorphisms on CWD zoonosis as well as the characteristics of experimental human CWD prions.

 

PRION 2016 TOKYO

 

In Conjunction with Asia Pacific Prion Symposium 2016

 

PRION 2016 Tokyo

 

Prion 2016

 

http://prion2016.org/dl/newsletter_03.pdf

 

Prion 2016

 

Purchase options Price * Issue Purchase USD 198.00

 

http://www.tandfonline.com/toc/kprn20/10/sup1

 

Cervid to human prion transmission

 

Kong, Qingzhong

 

Case Western Reserve University, Cleveland, OH, United States

 

Abstract

 

Prion disease is transmissible and invariably fatal. Chronic wasting disease (CWD) is the prion disease affecting deer, elk and moose, and it is a widespread and expanding epidemic affecting 22 US States and 2 Canadian provinces so far. CWD poses the most serious zoonotic prion transmission risks in North America because of huge venison consumption (>6 million deer/elk hunted and consumed annually in the USA alone), significant prion infectivity in muscles and other tissues/fluids from CWD-affected cervids, and usually high levels of individual exposure to CWD resulting from consumption of the affected animal among often just family and friends. However, we still do not know whether CWD prions can infect humans in the brain or peripheral tissues or whether clinical/asymptomatic CWD zoonosis has already occurred, and we have no essays to reliably detect CWD infection in humans. We hypothesize that:

 

(1) The classic CWD prion strain can infect humans at low levels in the brain and peripheral lymphoid tissues;

 

(2) The cervid-to-human transmission barrier is dependent on the cervid prion strain and influenced by the host (human) prion protein (PrP) primary sequence;

 

(3) Reliable essays can be established to detect CWD infection in humans;and

 

(4) CWD transmission to humans has already occurred. We will test these hypotheses in 4 Aims using transgenic (Tg) mouse models and complementary in vitro approaches.

 

Aim 1 will prove that the classical CWD strain may infect humans in brain or peripheral lymphoid tissues at low levels by conducting systemic bioassays in a set of "humanized" Tg mouse lines expressing common human PrP variants using a number of CWD isolates at varying doses and routes. Experimental "human CWD" samples will also be generated for Aim 3.

 

Aim 2 will test the hypothesis that the cervid-to-human prion transmission barrier is dependent on prion strain and influenced by the host (human) PrP sequence by examining and comparing the transmission efficiency and phenotypes of several atypical/unusual CWD isolates/strains as well as a few prion strains from other species that have adapted to cervid PrP sequence, utilizing the same panel of humanized Tg mouse lines as in Aim 1.

 

Aim 3 will establish reliable essays for detection and surveillance of CWD infection in humans by examining in details the clinical, pathological, biochemical and in vitro seeding properties of existing and future experimental "human CWD" samples generated from Aims 1-2 and compare them with those of common sporadic human Creutzfeldt-Jakob disease (sCJD) prions.

 

Aim 4 will attempt to detect clinical CWD-affected human cases by examining a significant number of brain samples from prion-affected human subjects in the USA and Canada who have consumed venison from CWD-endemic areas utilizing the criteria and essays established in Aim 3. The findings from this proposal will greatly advance our understandings on the potential and characteristics of cervid prion transmission in humans, establish reliable essays for CWD zoonosis and potentially discover the first case(s) of CWD infection in humans.

 

Public Health Relevance There are significant and increasing human exposure to cervid prions because chronic wasting disease (CWD, a widespread and highly infectious prion disease among deer and elk in North America) continues spreading and consumption of venison remains popular, but our understanding on cervid-to-human prion transmission is still very limited, raising public health concerns. This proposal aims to define the zoonotic risks of cervid prions and set up and apply essays to detect CWD zoonosis using mouse models and in vitro methods. The findings will greatly expand our knowledge on the potentials and characteristics of cervid prion transmission in humans, establish reliable essays for such infections and may discover the first case(s) of CWD infection in humans.

 

Funding Agency Agency National Institute of Health (NIH)

 

Institute National Institute of Neurological Disorders and Stroke (NINDS)

 

Type Research Project (R01)

 

Project # 1R01NS088604-01A1

 

Application # 9037884

 

Study Section Cellular and Molecular Biology of Neurodegeneration Study Section (CMND)

 

Program Officer Wong, May

 

Project Start 2015-09-30

 

Project End 2019-07-31

 

Budget Start 2015-09-30

 

Budget End 2016-07-31

 

Support Year 1

 

Fiscal Year 2015

 

Total Cost $337,507

 

Indirect Cost $118,756

 

Institution

 

Name Case Western Reserve University

 

Department Pathology

 

Type Schools of Medicine

 

DUNS # 077758407

 

City Cleveland

 

State OH

 

Country United States

 

Zip Code 44106

 

http://grantome.com/grant/NIH/R01-NS088604-01A1

 

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

 

We hypothesize that:

 

(1) The classic CWD prion strain can infect humans at low levels in the brain and peripheral lymphoid tissues;

 

(2) The cervid-to-human transmission barrier is dependent on the cervid prion strain and influenced by the host (human) prion protein (PrP) primary sequence;

 

(3) Reliable essays can be established to detect CWD infection in humans;and

 

(4) *** CWD transmission to humans has already occurred. *** We will test these hypotheses in 4 Aims using transgenic (Tg) mouse models and complementary in vitro approaches.

 

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

 

Key Molecular Mechanisms of TSEs

 

Zabel, Mark D.

 

Colorado State University-Fort Collins, Fort Collins, CO, United States Abstract Prion diseases, or transmissible spongiform encephalopathies (TSEs), are fatal neurodegenerative diseases affecting humans, cervids, bovids, and ovids. The absolute requirement of PrPC expression to generate prion diseases and the lack of instructional nucleic acid define prions as unique infectious agents. Prions exhibit species-specific tropism, inferring that unique prion strains exist that preferentially infct certain host species and confront transmission barriers to heterologous host species. However, transmission barriers are not absolute. Scientific consensus agrees that the sheep TSE scrapie probably breached the transmission barrier to cattle causing bovine spongiform encephalopathy that subsequently breached the human transmission barrier and likely caused several hundred deaths by a new-variant form of the human TSE Creutzfeldt-Jakob disease in the UK and Europe. The impact to human health, emotion and economies can still be felt in areas like farming, blood and organ donations and the threat of a latent TSE epidemic. This precedent raises the real possibility of other TSEs, like chronic wasting disease of cervids, overcoming similar human transmission barriers. A groundbreaking discovery made last year revealed that mice infected with heterologous prion strains facing significant transmission barriers replicated prions far more readily in spleens than brains6. Furthermore, these splenic prions exhibited weakened transmission barriers and expanded host ranges compared to neurogenic prions. These data question conventional wisdom of avoiding neural tissue to avoid prion xenotransmission, when more promiscuous prions may lurk in extraneural tissues. Data derived from work previously funded by NIH demonstrate that Complement receptors CD21/35 bind prions and high density PrPC and differentially impact prion disease depending on the prion isolate or strain used. Recent advances in live animal and whole organ imaging have led us to generate preliminary data to support novel, innovative approaches to assessing prion capture and transport. We plan to test our unifying hypothesis for this proposal that CD21/35 control the processes of peripheral prion capture, transport, strain selection and xenotransmission in the following specific aims. 1. Assess the role of CD21/35 in splenic prion strain selection and host range expansion. 2. Determine whether CD21/35 and C1q differentially bind distinct prion strains 3. Monitor the effects of CD21/35 on prion trafficking in real time and space 4. Assess the role of CD21/35 in incunabular prion trafficking

 

Public Health Relevance Transmissible spongiform encephalopathies, or prion diseases, are devastating illnesses that greatly impact public health, agriculture and wildlife in North America and around the world. The impact to human health, emotion and economies can still be felt in areas like farming, blood and organ donations and the threat of a latent TSE epidemic. This precedent raises the real possibility of other TSEs, like chronic wasting disease (CWD) of cervids, overcoming similar human transmission barriers. Early this year Canada reported its first case of BSE in over a decade audits first case of CWD in farmed elk in three years, underscoring the need for continued vigilance and research. Identifying mechanisms of transmission and zoonoses remains an extremely important and intense area of research that will benefit human and other animal populations.

 

Funding Agency Agency National Institute of Health (NIH)

 

Institute National Institute of Allergy and Infectious Diseases (NIAID)

 

Type High Priority, Short Term Project Award (R56)

 

Project # 1R56AI122273-01A1

 

Application # 9211114

 

Study Section Cellular and Molecular Biology of Neurodegeneration Study Section (CMND)

 

Program Officer Beisel, Christopher E

 

Project Start 2016-02-16

 

Project End 2017-01-31

 

Budget Start 2016-02-16

 

Budget End 2017-01-31

 

Support Year 1

 

Fiscal Year 2016

 

Total Cost

 

Indirect Cost Institution Name Colorado State University-Fort Collins

 

Department Microbiology/Immun/Virology

 

Type Schools of Veterinary Medicine

 

DUNS # 785979618 City Fort Collins

 

State CO

 

Country United States

 

Zip Code 80523

 

http://grantome.com/grant/NIH/R56-AI122273-01A1

 

PMCA Detection of CWD Infection in Cervid and Non-Cervid Species

 

Hoover, Edward Arthur

 

Colorado State University-Fort Collins, Fort Collins, CO, United States Abstract Chronic wasting disease (CWD) of deer and elk is an emerging highly transmissible prion disease now recognized in 18 States, 2 Canadian provinces, and Korea. We have shown that Infected deer harbor and shed high levels of infectious prions in saliva, blood, urine, and feces, and in the tissues generating those body fluids and excreta, thereby leading to facile transmission by direct contact and environmental contamination. We have also shown that CWD can infect some non-cervid species, thus the potential risk CWD represents to domestic animal species and to humans remains unknown. Whether prions borne in blood, saliva, nasal fluids, milk, or excreta are generated or modified in the proximate peripheral tissue sites, may differ in subtle ways from those generated in brain, or may be adapted for mucosal infection remain open questions. The increasing parallels in the pathogenesis between prion diseases and human neurodegenerative conditions, such as Alzheimer's and Parkinson's diseases, add relevance to CWD as a transmissible protein misfolding disease. The overall goal of this work is to elucidate the process of CWD prion transmission from mucosal secretory and excretory tissue sites by addressing these questions: (a) What are the kinetics and magnitude of CWD prion shedding post-exposure? (b) Are excreted prions biochemically distinct, or not, from those in the CNS? (c) Are peripheral epithelial or CNS tissues, or both, the source of excreted prions? and (d) Are excreted prions adapted for horizontal transmission via natural/trans-mucosal routes? The specific aims of this proposal are: (1) To determine the onset and consistency of CWD prion shedding in deer and cervidized mice; (2); To compare the biochemical and biophysical properties of excretory vs. CNS prions; (3) To determine the capacity of peripheral tissues to support replication of CWD prions; (4) To determine the protease- sensitive infectious fraction of excreted vs. CNS prions; and (5) To compare the mucosal infectivity of excretory vs. CNS prions. Understanding the mechanisms that enable efficient prion dissemination and shedding will help elucidate how horizontally transmissible prions evolve and succeed, and is the basis of this proposal. Understanding how infectious misfolded proteins (prions) are generated, trafficked, shed, and transmitted will aid in preventing, treating, and managing the risks associated with these agents and the diseases they cause.

 

Public Health Relevance Chronic wasting disease (CWD) of deer and elk is an emergent highly transmissible prion disease now recognized throughout the USA as well as in Canada and Korea. We have shown that infected deer harbor and shed high levels of infectious prions in saliva, blood, urine, and feces thereby leading to transmission by direct contact and environmental contamination. In that our studies have also shown that CWD can infect some non-cervid species, the potential risk CWD may represents to domestic animal species and humans remains unknown. The increasing parallels in the development of major human neurodegenerative conditions, such as Alzheimer's and Parkinson's diseases, and prion diseases add relevance to CWD as a model of a transmissible protein misfolding disease. Understanding how infectious misfolded proteins (prions) are generated and transmitted will aid in interrupting, treating, and managing the risks associated with these agents and the diseases they cause.

 

Funding Agency Agency National Institute of Health (NIH)

 

Institute National Institute of Neurological Disorders and Stroke (NINDS)

 

Type Research Project (R01)

 

Project # 4R01NS061902-07

 

Application # 9010980

 

Study Section Cellular and Molecular Biology of Neurodegeneration Study Section (CMND)

 

Program Officer Wong, May Project Start 2009-09-30

 

Project End 2018-02-28

 

Budget Start 2016-03-01

 

Budget End 2017-02-28

 

Support Year 7

 

Fiscal Year 2016

 

Total Cost $409,868

 

Indirect Cost $134,234 Institution Name Colorado State University-Fort Collins

 

Department Microbiology/Immun/Virology

 

Type Schools of Veterinary Medicine

 

DUNS # 785979618 City Fort Collins

 

State CO

 

Country United States

 

Zip Code 80523

 

http://grantome.com/grant/NIH/R01-NS061902-07

 

LOOKING FOR CWD IN HUMANS AS nvCJD or as an ATYPICAL CJD, LOOKING IN ALL THE WRONG PLACES $$$

 

*** These results would seem to suggest that CWD does indeed have zoonotic potential, at least as judged by the compatibility of CWD prions and their human PrPC target. Furthermore, extrapolation from this simple in vitro assay suggests that if zoonotic CWD occurred, it would most likely effect those of the PRNP codon 129-MM genotype and that the PrPres type would be similar to that found in the most common subtype of sCJD (MM1).***

 

https://www.landesbioscience.com/journals/prion/article/28124/?nocache=112223249

 

PRION 2015 CONFERENCE FT. COLLINS CWD RISK FACTORS TO HUMANS

 

*** LATE-BREAKING ABSTRACTS PRION 2015 CONFERENCE ***

 

O18

 

Zoonotic Potential of CWD Prions

 

Liuting Qing1, Ignazio Cali1,2, Jue Yuan1, Shenghai Huang3, Diane Kofskey1, Pierluigi Gambetti1, Wenquan Zou1, Qingzhong Kong1 1Case Western Reserve University, Cleveland, Ohio, USA, 2Second University of Naples, Naples, Italy, 3Encore Health Resources, Houston, Texas, USA

 

*** These results indicate that the CWD prion has the potential to infect human CNS and peripheral lymphoid tissues and that there might be asymptomatic human carriers of CWD infection.

 

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

 

***These results indicate that the CWD prion has the potential to infect human CNS and peripheral lymphoid tissues and that there might be asymptomatic human carriers of CWD infection.***

 

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

 

P.105: RT-QuIC models trans-species prion transmission

 

Kristen Davenport, Davin Henderson, Candace Mathiason, and Edward Hoover Prion Research Center; Colorado State University; Fort Collins, CO USA

 

Conversely, FSE maintained sufficient BSE characteristics to more efficiently convert bovine rPrP than feline rPrP. Additionally, human rPrP was competent for conversion by CWD and fCWD.

 

***This insinuates that, at the level of protein:protein interactions, the barrier preventing transmission of CWD to humans is less robust than previously estimated.

 

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

 

***This insinuates that, at the level of protein:protein interactions, the barrier preventing transmission of CWD to humans is less robust than previously estimated.***

 

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

 

https://prion2015.files.wordpress.com/2015/05/programguide1.pdf

 

*** PRICE OF CWD TSE PRION POKER GOES UP 2014 ***

 

Transmissible Spongiform Encephalopathy TSE PRION update January 2, 2014

 

*** chronic wasting disease, there was no absolute barrier to conversion of the human prion protein.

 

*** Furthermore, the form of human PrPres produced in this in vitro assay when seeded with CWD, resembles that found in the most common human prion disease, namely sCJD of the MM1 subtype.

 

http://wwwnc.cdc.gov/eid/article/20/1/13-0858_article.htm

 

http://chronic-wasting-disease.blogspot.com/2014/01/molecular-barriers-to-zoonotic.html

 

*** These results would seem to suggest that CWD does indeed have zoonotic potential, at least as judged by the compatibility of CWD prions and their human PrPC target. Furthermore, extrapolation from this simple in vitro assay suggests that if zoonotic CWD occurred, it would most likely effect those of the PRNP codon 129-MM genotype and that the PrPres type would be similar to that found in the most common subtype of sCJD (MM1).***

 

https://www.landesbioscience.com/journals/prion/article/28124/?nocache=112223249

 

*** The potential impact of prion diseases on human health was greatly magnified by the recognition that interspecies transfer of BSE to humans by beef ingestion resulted in vCJD. While changes in animal feed constituents and slaughter practices appear to have curtailed vCJD, there is concern that CWD of free-ranging deer and elk in the U.S. might also cross the species barrier. Thus, consuming venison could be a source of human prion disease. Whether BSE and CWD represent interspecies scrapie transfer or are newly arisen prion diseases is unknown. Therefore, the possibility of transmission of prion disease through other food animals cannot be ruled out. There is evidence that vCJD can be transmitted through blood transfusion. There is likely a pool of unknown size of asymptomatic individuals infected with vCJD, and there may be asymptomatic individuals infected with the CWD equivalent. These circumstances represent a potential threat to blood, blood products, and plasma supplies.

 

http://cdmrp.army.mil/prevfunded/nprp/NPRP_Summit_Final_Report.pdf

 

***********CJD REPORT 1994 increased risk for consumption of veal and venison and lamb***********

 

CREUTZFELDT JAKOB DISEASE SURVEILLANCE IN THE UNITED KINGDOM THIRD ANNUAL REPORT AUGUST 1994

 

Consumption of venison and veal was much less widespread among both cases and controls. For both of these meats there was evidence of a trend with increasing frequency of consumption being associated with increasing risk of CJD. (not nvCJD, but sporadic CJD...tss)

 

These associations were largely unchanged when attention was restricted to pairs with data obtained from relatives. ...

 

Table 9 presents the results of an analysis of these data.

 

There is STRONG evidence of an association between ‘’regular’’ veal eating and risk of CJD (p = .0.01).

 

Individuals reported to eat veal on average at least once a year appear to be at 13 TIMES THE RISK of individuals who have never eaten veal.

 

There is, however, a very wide confidence interval around this estimate. There is no strong evidence that eating veal less than once per year is associated with increased risk of CJD (p = 0.51).

 

The association between venison eating and risk of CJD shows similar pattern, with regular venison eating associated with a 9 FOLD INCREASE IN RISK OF CJD (p = 0.04).

 

There is some evidence that risk of CJD INCREASES WITH INCREASING FREQUENCY OF LAMB EATING (p = 0.02).

 

The evidence for such an association between beef eating and CJD is weaker (p = 0.14). When only controls for whom a relative was interviewed are included, this evidence becomes a little STRONGER (p = 0.08).

 

snip...

 

It was found that when veal was included in the model with another exposure, the association between veal and CJD remained statistically significant (p = < 0.05 for all exposures), while the other exposures ceased to be statistically significant (p = > 0.05).

 

snip...

 

In conclusion, an analysis of dietary histories revealed statistical associations between various meats/animal products and INCREASED RISK OF CJD. When some account was taken of possible confounding, the association between VEAL EATING AND RISK OF CJD EMERGED AS THE STRONGEST OF THESE ASSOCIATIONS STATISTICALLY. ...

 

snip...

 

In the study in the USA, a range of foodstuffs were associated with an increased risk of CJD, including liver consumption which was associated with an apparent SIX-FOLD INCREASE IN THE RISK OF CJD. By comparing the data from 3 studies in relation to this particular dietary factor, the risk of liver consumption became non-significant with an odds ratio of 1.2 (PERSONAL COMMUNICATION, PROFESSOR A. HOFMAN. ERASMUS UNIVERSITY, ROTTERDAM). (???...TSS)

 

snip...see full report ;

 

http://collections.europarchive.org/tna/20090505194948/http://bseinquiry.gov.uk/files/yb/1994/08/00004001.pdf

 

CJD9/10022

 

October 1994

 

Mr R.N. Elmhirst Chairman British Deer Farmers Association Holly Lodge Spencers Lane BerksWell Coventry CV7 7BZ

 

Dear Mr Elmhirst,

 

CREUTZFELDT-JAKOB DISEASE (CJD) SURVEILLANCE UNIT REPORT

 

Thank you for your recent letter concerning the publication of the third annual report from the CJD Surveillance Unit. I am sorry that you are dissatisfied with the way in which this report was published.

 

The Surveillance Unit is a completely independant outside body and the Department of Health is committed to publishing their reports as soon as they become available. In the circumstances it is not the practice to circulate the report for comment since the findings of the report would not be amended. In future we can ensure that the British Deer Farmers Association receives a copy of the report in advance of publication.

 

The Chief Medical Officer has undertaken to keep the public fully informed of the results of any research in respect of CJD. This report was entirely the work of the unit and was produced completely independantly of the the Department.

 

The statistical results reqarding the consumption of venison was put into perspective in the body of the report and was not mentioned at all in the press release. Media attention regarding this report was low key but gave a realistic presentation of the statistical findings of the Unit. This approach to publication was successful in that consumption of venison was highlighted only once by the media ie. in the News at one television proqramme.

 

I believe that a further statement about the report, or indeed statistical links between CJD and consumption of venison, would increase, and quite possibly give damaging credence, to the whole issue. From the low key media reports of which I am aware it seems unlikely that venison consumption will suffer adversely, if at all.

 

http://web.archive.org/web/20030511010117/http://www.bseinquiry.gov.uk/files/yb/1994/10/00003001.pdf

 

Monday, May 02, 2016

 

*** Zoonotic Potential of CWD Prions: An Update Prion 2016 Tokyo ***

 

http://chronic-wasting-disease.blogspot.com/2016/05/zoonotic-potential-of-cwd-prions-update.html

 

*** PRION 2014 CONFERENCE CHRONIC WASTING DISEASE CWD

 

http://chronic-wasting-disease.blogspot.com/2014/06/prion-2014-chronic-wasting-disease-cwd.html

 

*** PPo3-7: Prion Transmission from Cervids to Humans is Strain-dependent

 

*** 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.

 

PPo2-27:

 

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

 

*** 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

 

*** The data presented here substantiate and expand previous reports on the existence of different CWD strains.

 

https://www.landesbioscience.com/journals/prion/Prion4-3-PPo2.pdf

 

Envt.07:

 

Pathological Prion Protein (PrPTSE) in Skeletal Muscles of Farmed and Free Ranging White-Tailed Deer Infected with Chronic Wasting Disease

 

***The presence and seeding activity of PrPTSE in skeletal muscle from CWD-infected cervids suggests prevention of such tissue in the human diet as a precautionary measure for food safety, pending on further clarification of whether CWD may be transmissible to humans.

 

 http://www.landesbioscience.com/journals/prion/Prion5-Supp-PrionEnvironment.pdf?nocache=1333529975

 

>>>CHRONIC WASTING DISEASE , THERE WAS NO ABSOLUTE BARRIER TO CONVERSION OF THE HUMAN PRION PROTEIN<<<

 

*** PRICE OF CWD TSE PRION POKER GOES UP 2014 ***

 

Transmissible Spongiform Encephalopathy TSE PRION update January 2, 2014

 

Wednesday, January 01, 2014

 

Molecular Barriers to Zoonotic Transmission of Prions

 

*** chronic wasting disease, there was no absolute barrier to conversion of the human prion protein.

 

*** Furthermore, the form of human PrPres produced in this in vitro assay when seeded with CWD, resembles that found in the most common human prion disease, namely sCJD of the MM1 subtype.

 

http://wwwnc.cdc.gov/eid/article/20/1/13-0858_article.htm

 

http://chronic-wasting-disease.blogspot.com/2014/01/molecular-barriers-to-zoonotic.html

 

Using in vitro prion replication for high sensitive detection of prions and prionlike proteins and for understanding mechanisms of transmission.

 

Claudio Soto

 

Mitchell Center for Alzheimer's diseases and related Brain disorders, Department of Neurology, University of Texas Medical School at Houston.

 

Prion and prion-like proteins are misfolded protein aggregates with the ability to selfpropagate to spread disease between cells, organs and in some cases across individuals. I n T r a n s m i s s i b l e s p o n g i f o r m encephalopathies (TSEs), prions are mostly composed by a misfolded form of the prion protein (PrPSc), which propagates by transmitting its misfolding to the normal prion protein (PrPC). The availability of a procedure to replicate prions in the laboratory may be important to study the mechanism of prion and prion-like spreading and to develop high sensitive detection of small quantities of misfolded proteins in biological fluids, tissues and environmental samples. Protein Misfolding Cyclic Amplification (PMCA) is a simple, fast and efficient methodology to mimic prion replication in the test tube. PMCA is a platform technology that may enable amplification of any prion-like misfolded protein aggregating through a seeding/nucleation process. In TSEs, PMCA is able to detect the equivalent of one single molecule of infectious PrPSc and propagate prions that maintain high infectivity, strain properties and species specificity. Using PMCA we have been able to detect PrPSc in blood and urine of experimentally infected animals and humans affected by vCJD with high sensitivity and specificity. Recently, we have expanded the principles of PMCA to amplify amyloid-beta (Aβ) and alphasynuclein (α-syn) aggregates implicated in Alzheimer's and Parkinson's diseases, respectively. Experiments are ongoing to study the utility of this technology to detect Aβ and α-syn aggregates in samples of CSF and blood from patients affected by these diseases.

 

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

 

***Recently, we have been using PMCA to study the role of environmental prion contamination on the horizontal spreading of TSEs. These experiments have focused on the study of the interaction of prions with plants and environmentally relevant surfaces. Our results show that plants (both leaves and roots) bind tightly to prions present in brain extracts and excreta (urine and feces) and retain even small quantities of PrPSc for long periods of time. Strikingly, ingestion of prioncontaminated leaves and roots produced disease with a 100% attack rate and an incubation period not substantially longer than feeding animals directly with scrapie brain homogenate. Furthermore, plants can uptake prions from contaminated soil and transport them to different parts of the plant tissue (stem and leaves). Similarly, prions bind tightly to a variety of environmentally relevant surfaces, including stones, wood, metals, plastic, glass, cement, etc. Prion contaminated surfaces efficiently transmit prion disease when these materials were directly injected into the brain of animals and strikingly when the contaminated surfaces were just placed in the animal cage. These findings demonstrate that environmental materials can efficiently bind infectious prions and act as carriers of infectivity, suggesting that they may play an important role in the horizontal transmission of the disease.

 

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

 

Since its invention 13 years ago, PMCA has helped to answer fundamental questions of prion propagation and has broad applications in research areas including the food industry, blood bank safety and human and veterinary disease diagnosis.

 

https://prion2015.files.wordpress.com/2015/05/programguide1.pdf

 

see ;

 

with CWD TSE Prions, I am not sure there is any absolute yet, other than what we know with transmission studies, and we know tse prion kill, and tse prion are bad. science shows to date, that indeed soil, dirt, some better than others, can act as a carrier. same with objects, farm furniture. take it with how ever many grains of salt you wish, or not. if load factor plays a role in the end formula, then everything should be on the table, in my opinion. see ;

 

***Recently, we have been using PMCA to study the role of environmental prion contamination on the horizontal spreading of TSEs. These experiments have focused on the study of the interaction of prions with plants and environmentally relevant surfaces. Our results show that plants (both leaves and roots) bind tightly to prions present in brain extracts and excreta (urine and feces) and retain even small quantities of PrPSc for long periods of time. Strikingly, ingestion of prioncontaminated leaves and roots produced disease with a 100% attack rate and an incubation period not substantially longer than feeding animals directly with scrapie brain homogenate. Furthermore, plants can uptake prions from contaminated soil and transport them to different parts of the plant tissue (stem and leaves). Similarly, prions bind tightly to a variety of environmentally relevant surfaces, including stones, wood, metals, plastic, glass, cement, etc. Prion contaminated surfaces efficiently transmit prion disease when these materials were directly injected into the brain of animals and strikingly when the contaminated surfaces were just placed in the animal cage. These findings demonstrate that environmental materials can efficiently bind infectious prions and act as carriers of infectivity, suggesting that they may play an important role in the horizontal transmission of the disease.

 

Since its invention 13 years ago, PMCA has helped to answer fundamental questions of prion propagation and has broad applications in research areas including the food industry, blood bank safety and human and veterinary disease diagnosis.

 

https://prion2015.files.wordpress.com/2015/05/programguide1.pdf

 

see ;

 

http://www.tandfonline.com/doi/pdf/10.4161/pri.28467

 

Oral Transmissibility of Prion Disease Is Enhanced by Binding to Soil Particles

 

Author Summary

 

Transmissible spongiform encephalopathies (TSEs) are a group of incurable neurological diseases likely caused by a misfolded form of the prion protein. TSEs include scrapie in sheep, bovine spongiform encephalopathy (‘‘mad cow’’ disease) in cattle, chronic wasting disease in deer and elk, and Creutzfeldt-Jakob disease in humans. Scrapie and chronic wasting disease are unique among TSEs because they can be transmitted between animals, and the disease agents appear to persist in environments previously inhabited by infected animals. Soil has been hypothesized to act as a reservoir of infectivity and to bind the infectious agent. In the current study, we orally dosed experimental animals with a common clay mineral, montmorillonite, or whole soils laden with infectious prions, and compared the transmissibility to unbound agent. We found that prions bound to montmorillonite and whole soils remained orally infectious, and, in most cases, increased the oral transmission of disease compared to the unbound agent. The results presented in this study suggest that soil may contribute to environmental spread of TSEs by increasing the transmissibility of small amounts of infectious agent in the environment.

 

https://www.aphis.usda.gov/emergency_response/downloads/tools/johnson%20et%20al%20prions%20in%20soil.pdf

 

tse prion soil

 

http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0058630

 

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3567181/pdf/ppat.1003113.pdf

 

http://www.nature.com/srep/2015/150210/srep08358/full/srep08358.html?WT.ec_id=SREP-639-20150217

 

http://www.cell.com/cell-reports/pdfExtended/S2211-1247(15)00437-4

 

Saturday, May 28, 2016

 

*** Infection and detection of PrPCWD in soil from CWD infected farm in Korea Prion 2016 Tokyo ***

 

http://chronic-wasting-disease.blogspot.com/2016/05/infection-and-detection-of-prpcwd-in.html

 

Wednesday, December 16, 2015

 

Objects in contact with classical scrapie sheep act as a reservoir for scrapie transmission

 

http://journal.frontiersin.org/article/10.3389/fvets.2015.00032/full

 

The sources of dust borne prions are unknown but it seems reasonable to assume that faecal, urine, skin, parturient material and saliva-derived prions may contribute to this mobile environmental reservoir of infectivity. This work highlights a possible transmission route for scrapie within the farm environment, and this is likely to be paralleled in CWD which shows strong similarities with scrapie in terms of prion dissemination and disease transmission. The data indicate that the presence of scrapie prions in dust is likely to make the control of these diseases a considerable challenge.

 

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4397813/pdf/13567_2015_Article_176.pdf

 

>>>Particle-associated PrPTSE molecules may migrate from locations of deposition via transport processes affecting soil particles, including entrainment in and movement with air and overland flow. <<<

 

Fate of Prions in Soil: A Review

 

Christen B. Smith, Clarissa J. Booth, and Joel A. Pedersen*

 

Several reports have shown that prions can persist in soil for several years. Significant interest remains in developing methods that could be applied to degrade PrPTSE in naturally contaminated soils. Preliminary research suggests that serine proteases and the microbial consortia in stimulated soils and compost may partially degrade PrPTSE. Transition metal oxides in soil (viz. manganese oxide) may also mediate prion inactivation. Overall, the effect of prion attachment to soil particles on its persistence in the environment is not well understood, and additional study is needed to determine its implications on the environmental transmission of scrapie and CWD.

 

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3160281/

 

P.161: Prion soil binding may explain efficient horizontal CWD transmission

 

Conclusion. Silty clay loam exhibits highly efficient prion binding, inferring a durable environmental reservoir, and an efficient mechanism for indirect horizontal CWD transmission.

 

https://prion2015.files.wordpress.com/2015/05/prion2015abstracts.pdf

 

>>>Another alternative would be an absolute prohibition on the movement of deer within the state for any purpose. While this alternative would significantly reduce the potential spread of CWD, it would also have the simultaneous effect of preventing landowners and land managers from implementing popular management strategies involving the movement of deer, and would deprive deer breeders of the ability to engage in the business of buying and selling breeder deer. Therefore, this alternative was rejected because the department determined that it placed an avoidable burden on the regulated community.<<<

 

Wednesday, December 16, 2015

 

Objects in contact with classical scrapie sheep act as a reservoir for scrapie transmission

 

Objects in contact with classical scrapie sheep act as a reservoir for scrapie transmission

 

Timm Konold1*, Stephen A. C. Hawkins2, Lisa C. Thurston3, Ben C. Maddison4, Kevin C. Gough5, Anthony Duarte1 and Hugh A. Simmons1

 

1 Animal Sciences Unit, Animal and Plant Health Agency Weybridge, Addlestone, UK, 2 Pathology Department, Animal and Plant Health Agency Weybridge, Addlestone, UK, 3 Surveillance and Laboratory Services, Animal and Plant Health Agency Penrith, Penrith, UK, 4 ADAS UK, School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington, UK, 5 School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington, UK

 

Classical scrapie is an environmentally transmissible prion disease of sheep and goats. Prions can persist and remain potentially infectious in the environment for many years and thus pose a risk of infecting animals after re-stocking. In vitro studies using serial protein misfolding cyclic amplification (sPMCA) have suggested that objects on a scrapie affected sheep farm could contribute to disease transmission. This in vivo study aimed to determine the role of field furniture (water troughs, feeding troughs, fencing, and other objects that sheep may rub against) used by a scrapie-infected sheep flock as a vector for disease transmission to scrapie-free lambs with the prion protein genotype VRQ/VRQ, which is associated with high susceptibility to classical scrapie. When the field furniture was placed in clean accommodation, sheep became infected when exposed to either a water trough (four out of five) or to objects used for rubbing (four out of seven). This field furniture had been used by the scrapie-infected flock 8 weeks earlier and had previously been shown to harbor scrapie prions by sPMCA. Sheep also became infected (20 out of 23) through exposure to contaminated field furniture placed within pasture not used by scrapie-infected sheep for 40 months, even though swabs from this furniture tested negative by PMCA. This infection rate decreased (1 out of 12) on the same paddock after replacement with clean field furniture. Twelve grazing sheep exposed to field furniture not in contact with scrapie-infected sheep for 18 months remained scrapie free. The findings of this study highlight the role of field furniture used by scrapie-infected sheep to act as a reservoir for disease re-introduction although infectivity declines considerably if the field furniture has not been in contact with scrapie-infected sheep for several months. PMCA may not be as sensitive as VRQ/VRQ sheep to test for environmental contamination.

 

snip...

 

Discussion

 

Classical scrapie is an environmentally transmissible disease because it has been reported in naïve, supposedly previously unexposed sheep placed in pastures formerly occupied by scrapie-infected sheep (4, 19, 20). Although the vector for disease transmission is not known, soil is likely to be an important reservoir for prions (2) where – based on studies in rodents – prions can adhere to minerals as a biologically active form (21) and remain infectious for more than 2 years (22). Similarly, chronic wasting disease (CWD) has re-occurred in mule deer housed in paddocks used by infected deer 2 years earlier, which was assumed to be through foraging and soil consumption (23).

 

Our study suggested that the risk of acquiring scrapie infection was greater through exposure to contaminated wooden, plastic, and metal surfaces via water or food troughs, fencing, and hurdles than through grazing. Drinking from a water trough used by the scrapie flock was sufficient to cause infection in sheep in a clean building. Exposure to fences and other objects used for rubbing also led to infection, which supported the hypothesis that skin may be a vector for disease transmission (9). The risk of these objects to cause infection was further demonstrated when 87% of 23 sheep presented with PrPSc in lymphoid tissue after grazing on one of the paddocks, which contained metal hurdles, a metal lamb creep and a water trough in contact with the scrapie flock up to 8 weeks earlier, whereas no infection had been demonstrated previously in sheep grazing on this paddock, when equipped with new fencing and field furniture. When the contaminated furniture and fencing were removed, the infection rate dropped significantly to 8% of 12 sheep, with soil of the paddock as the most likely source of infection caused by shedding of prions from the scrapie-infected sheep in this paddock up to a week earlier.

 

This study also indicated that the level of contamination of field furniture sufficient to cause infection was dependent on two factors: stage of incubation period and time of last use by scrapie-infected sheep. Drinking from a water trough that had been used by scrapie sheep in the predominantly pre-clinical phase did not appear to cause infection, whereas infection was shown in sheep drinking from the water trough used by scrapie sheep in the later stage of the disease. It is possible that contamination occurred through shedding of prions in saliva, which may have contaminated the surface of the water trough and subsequently the water when it was refilled. Contamination appeared to be sufficient to cause infection only if the trough was in contact with sheep that included clinical cases. Indeed, there is an increased risk of bodily fluid infectivity with disease progression in scrapie (24) and CWD (25) based on PrPSc detection by sPMCA. Although ultraviolet light and heat under natural conditions do not inactivate prions (26), furniture in contact with the scrapie flock, which was assumed to be sufficiently contaminated to cause infection, did not act as vector for disease if not used for 18 months, which suggest that the weathering process alone was sufficient to inactivate prions.

 

PrPSc detection by sPMCA is increasingly used as a surrogate for infectivity measurements by bioassay in sheep or mice. In this reported study, however, the levels of PrPSc present in the environment were below the limit of detection of the sPMCA method, yet were still sufficient to cause infection of in-contact animals. In the present study, the outdoor objects were removed from the infected flock 8 weeks prior to sampling and were positive by sPMCA at very low levels (2 out of 37 reactions). As this sPMCA assay also yielded 2 positive reactions out of 139 in samples from the scrapie-free farm, the sPMCA assay could not detect PrPSc on any of the objects above the background of the assay. False positive reactions with sPMCA at a low frequency associated with de novo formation of infectious prions have been reported (27, 28). This is in contrast to our previous study where we demonstrated that outdoor objects that had been in contact with the scrapie-infected flock up to 20 days prior to sampling harbored PrPSc that was detectable by sPMCA analysis [4 out of 15 reactions (12)] and was significantly more positive by the assay compared to analogous samples from the scrapie-free farm. This discrepancy could be due to the use of a different sPMCA substrate between the studies that may alter the efficiency of amplification of the environmental PrPSc. In addition, the present study had a longer timeframe between the objects being in contact with the infected flock and sampling, which may affect the levels of extractable PrPSc. Alternatively, there may be potentially patchy contamination of this furniture with PrPSc, which may have been missed by swabbing. The failure of sPMCA to detect CWD-associated PrP in saliva from clinically affected deer despite confirmation of infectivity in saliva-inoculated transgenic mice was associated with as yet unidentified inhibitors in saliva (29), and it is possible that the sensitivity of sPMCA is affected by other substances in the tested material. In addition, sampling of amplifiable PrPSc and subsequent detection by sPMCA may be more difficult from furniture exposed to weather, which is supported by the observation that PrPSc was detected by sPMCA more frequently in indoor than outdoor furniture (12). A recent experimental study has demonstrated that repeated cycles of drying and wetting of prion-contaminated soil, equivalent to what is expected under natural weathering conditions, could reduce PMCA amplification efficiency and extend the incubation period in hamsters inoculated with soil samples (30). This seems to apply also to this study even though the reduction in infectivity was more dramatic in the sPMCA assays than in the sheep model. Sheep were not kept until clinical end-point, which would have enabled us to compare incubation periods, but the lack of infection in sheep exposed to furniture that had not been in contact with scrapie sheep for a longer time period supports the hypothesis that prion degradation and subsequent loss of infectivity occurs even under natural conditions.

 

In conclusion, the results in the current study indicate that removal of furniture that had been in contact with scrapie-infected animals should be recommended, particularly since cleaning and decontamination may not effectively remove scrapie infectivity (31), even though infectivity declines considerably if the pasture and the field furniture have not been in contact with scrapie-infected sheep for several months. As sPMCA failed to detect PrPSc in furniture that was subjected to weathering, even though exposure led to infection in sheep, this method may not always be reliable in predicting the risk of scrapie infection through environmental contamination. These results suggest that the VRQ/VRQ sheep model may be more sensitive than sPMCA for the detection of environmentally associated scrapie, and suggest that extremely low levels of scrapie contamination are able to cause infection in susceptible sheep genotypes.

 

Keywords: classical scrapie, prion, transmissible spongiform encephalopathy, sheep, field furniture, reservoir, serial protein misfolding cyclic amplification

 

http://journal.frontiersin.org/article/10.3389/fvets.2015.00032/full

 

Wednesday, December 16, 2015

 

*** Objects in contact with classical scrapie sheep act as a reservoir for scrapie transmission ***

 

http://scrapie-usa.blogspot.com/2015/12/objects-in-contact-with-classical.html

 

Monday, May 02, 2016

 

*** Zoonotic Potential of CWD Prions: An Update Prion 2016 Tokyo ***

 

http://chronic-wasting-disease.blogspot.com/2016/05/zoonotic-potential-of-cwd-prions-update.html

 

***at present, no cervid PrP allele conferring absolute resistance to prion infection has been identified.

 

P-145 Estimating chronic wasting disease resistance in cervids using real time quaking- induced conversion

 

Nicholas J Haley1, Rachel Rielinqer2, Kristen A Davenport3, W. David Walter4, Katherine I O'Rourke5, Gordon Mitchell6, Juergen A Richt2

 

1 Department of Microbiology and Immunology, Midwestern University, United States; 2Department of Diagnostic Medicine and Pathobiology, Kansas State University; 3Prion Research Center; Colorado State University; 4U.S. Geological Survey, Pennsylvania Cooperative Fish and Wildlife Research Unit; 5Agricultural Research Service, United States Department of Agriculture; 6Canadian Food Inspection Agency, National and OlE Reference Laboratory for Scrapie and CWO

 

In mammalian species, the susceptibility to prion diseases is affected, in part, by the sequence of the host's prion protein (PrP). In sheep, a gradation from scrapie susceptible to resistant has been established both in vivo and in vitro based on the amino acids present at PrP positions 136, 154, and 171, which has led to global breeding programs to reduce the prevalence of scrapie in domestic sheep. In cervids, resistance is commonly characterized as a delayed progression of chronic wasting disease (CWD); at present, no cervid PrP allele conferring absolute resistance to prion infection has been identified. To model the susceptibility of various naturally-occurring and hypothetical cervid PrP alleles in vitro, we compared the amplification rates and efficiency of various CWD isolates in recombinant PrPC using real time quaking-induced conversion. We hypothesized that amplification metrics of these isolates in cervid PrP substrates would correlate to in vivo susceptibility - allowing susceptibility prediction for alleles found at 10 frequency in nature, and that there would be an additive effect of multiple resistant codons in hypothetical alleles. Our studies demonstrate that in vitro amplification metrics predict in vivo susceptibility, and that alleles with multiple codons, each influencing resistance independently, do not necessarily contribute additively to resistance. Importantly, we found that the white-tailed deer 226K substrate exhibited the slowest amplification rate among those evaluated, suggesting that further investigation of this allele and its resistance in vivo are warranted to determine if absolute resistance to CWD is possible.

 

***at present, no cervid PrP allele conferring absolute resistance to prion infection has been identified.

 

PRION 2016 CONFERENCE TOKYO

 

http://prion2016.org/dl/newsletter_03.pdf

 

Prion protein gene sequence and chronic wasting disease susceptibility in white-tailed deer (Odocoileus virginianus)

 

Adam L Brandt, Amy C Kelly, Michelle L Green, Paul Shelton, Jan Novakofski & Nohra E Mateus-Pinilla To cite this article: Adam L Brandt, Amy C Kelly, Michelle L Green, Paul Shelton, Jan Novakofski & Nohra E Mateus-Pinilla (2015) Prion protein gene sequence and chronic wasting disease susceptibility in white-tailed deer (Odocoileus virginianus), Prion, 9:6, 449-462, DOI: 10.1080/19336896.2015.1115179 To link to this article: http://dx.doi.org/10.1080/19336896.2015.1115179

 

Prion, 9:449–462, 2015 Published with license by Taylor & Francis Group, LLC ISSN: 1933-6896 print / 1933-690X online DOI: 10.1080/19336896.2015.1115179

 

RESEARCH PAPER Prion protein gene sequence and chronic wasting disease susceptibility in white-tailed deer (Odocoileus virginianus) Adam L Brandt1, Amy C Kelly1, Michelle L Green1,2, Paul Shelton3, Jan Novakofski2,*, and Nohra E Mateus-Pinilla1,2 1Illinois Natural History Survey; University of Illinois at Urbana-Champaign; Urbana, IL USA; 2Department of Animal Sciences; University of Illinois at Urbana-Champaign; Urbana, IL USA; 3Illinois Department of Natural Resources; Division of Wildlife Resources; Springfield, IL USA

 

ABSTRACT.

 

The sequence of the prion protein gene (PRNP) affects susceptibility to spongiform encephalopathies, or prion diseases in many species. In white-tailed deer, both coding and noncoding single nucleotide polymorphisms have been identified in this gene that correlate to chronic wasting disease (CWD) susceptibility. Previous studies examined individual nucleotide or amino acid mutations; here we examine all nucleotide polymorphisms and their combined effects on CWD. A 626 bp region of PRNP was examined from 703 free-ranging white-tailed deer. Deer were sampled between 2002 and 2010 by hunter harvest or government culling in Illinois and Wisconsin. Fourteen variable nucleotide positions were identified (4 new and 10 previously reported). We identified 68 diplotypes comprised of 24 predicted haplotypes, with the most common diplotype occurring in 123 individuals. Diplotypes that were found exclusively among positive or negative animals were rare, each occurring in less than 1% of the deer studied. Only one haplotype (C, odds ratio 0.240) and 2 diplotypes (AC and BC, odds ratios of 0.161 and 0.108 respectively) has significant associations with CWD resistance. Each contains mutations (one synonymous nucleotide 555C/T and one nonsynonymous nucleotide 286G/A) at positions reported to be significantly associated with reduced CWD susceptibility. Results suggest that deer populations with higher frequencies of haplotype C or diplotypes AC and BC might have a reduced risk for CWD infection – while populations with lower frequencies may have higher risk for infection. Understanding the genetic basis of CWD has improved our ability to assess herd susceptibility and direct management efforts within CWD infected areas.

 

Adam L Brandt, Amy C Kelly, Michelle L Green, Paul Shelton, Jan Novakofski, and Nohra E Mateus-Pinilla *Correspondence to: Jan Novakofski; Email: jnova@illinois.edu Received September 21, 2015; Revised October 23, 2015; Accepted October 23, 2015. Color versions of one or more of the figures in the article can be found online atwww.tandfonline.com/kprn. This is an Open Access article distributed under the terms of the Creative Commons Attribution-Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. The moral rights of the named author(s) have been asserted.

 

DISCUSSION

 

In this study, we find reduced susceptibility to CWD infection among white-tailed deer with haplotype C (Table 2). We still observed individual deer positive for CWD with this haplotype, demonstrating a reduced susceptibility rather than a complete genetic resistance as is seen with other TSEs (e.g., scrapie36,37). This haplotype had 2 different polymorphisms, 1 synonymous and 1 non-synonymous, both reported to be associated with decreased infection; nt286A (aa96S) and nt555T.10,26,29,30 Other haplotypes have similar mutations at nt286 and nt555 (e.g., haplotypes I, Q, and S); though, within the CWD infection area these haplotypes are not found at all (haplotype Q), occur infrequently (f < 0.01, haplotypes I and S), or are found exclusively among positive deer (haplotype I). A number of other haplotypes have the same mutations at either nt286 or nt555; again most are absent (haplotypes H, V, W and X), infrequent (f < 0.01, haplotypes N and P), or are found abundantly among positive deer (haplotype B) in the CWD infection area (Table 2). Rarity of these haplotypes prevents any meaningful association with changes in susceptibility (Table 2). The effects of mutations at nt286 and nt555 alone or in concert are unclear as other haplotypes with these polymorphisms occur infrequently and with varied susceptibility. An even larger sampling may be necessary to resolve this interaction.

 

Neither haplotypes with aa95H (nt285C) had a significantly reduced susceptibility to CWD (Table 2). Some previous studies reported the occurrence of this mutation among CWD negative deer only, which was interpreted as CWD resistance.26,29 In this study and in the study by Kelly et al.10 the aa95H mutation was found among deer positive for CWD; however, we find in a larger sampling (ND240) the frequency of aa95H to be lower than that found by Kelly et al.10 and not significantly associated with resistance. We cannot preclude the importance of this mutation given that a significant difference in disease susceptibility may be possible with an even larger sample size providing greater statistical power (data not shown).

 

The presence of aa96S has been associated with slowed disease progression, longer life span among captive deer,26,27 and does not appear to affect the rate at which prions are shed from infected individuals.38 Additionally, CWD infected mule deer have been found to excrete pathogenic prions while asymptomatic. 39 This contributes to concerns that wild deer with aa96S may be shedding infectious prions into the environment for longer periods of time than deer lacking the mutation, but are not symptomatic or detectable by immunohistochemical procedures. On the other hand, studies using epidemiological modeling suggest that deer with aa96S under certain conditions may have a selective advantage for CWD resistance over those without.40 With our data, we are unable to make accurate conclusions about detection, longevity, or increased risks of exposure to infectious prions. Nonetheless, our results do corroborate the importance of the polymorphism at G96S in reduced CWD susceptibility (Table 5).26,30

 

Kelly et al.10 found a negative correlation between the number of nucleotide deviations from the PRNP consensus sequence and CWD infection. The database derived consensus sequence reported is the same as the most common haplotype (haplotype A) in this study (Table 1). Haplotype C has 2 deviations from haplotype A; other haplotypes were found containing more deviations but were exceedingly rare (Table 1). These haplotypes (namely haplotypes I, N, Q, S, and X) were largely absent among CWD positive deer (only 2 positive deer were found each with a single copy of haplotype I) and their combined frequency was less than 1%. An increased number of polymorphisms may improve resistance to CWD, but the large sample size of this study (ND703) suggests that haplotypes with more than 2 nucleotide deviations are rare and would not be likely to have an appreciable effect on resistance or susceptibility within the population.

 

Examination of PRNP diplotypes revealed that individuals with at least one copy of haplotype C (specifically AC and BC) were less likely to test positive for CWD (Table 4). Other diplotypes containing at least one copy of haplotype C (mutations at aa96S and nt555T) had a low frequency of occurrence (<1 41="" a="" account="" additional="" address="" age="" all="" always="" analyses="" and="" animals.="" animals="" any="" are="" area.="" area="" as="" association="" at="" attempted="" available="" average="" avoid="" background.29="" basis="" be="" been="" between="" bias.="" but="" by="" c="" cases="" circumstances="" conditions="" confounding="" control="" controlled="" could="" counties="" county="" cwd.="" cwd="" decreasing="" deer43-45="" deer="" design="" determining="" diplotypes="" disease="" distances="" div="" due="" examined="" experimental="" exposed="" factor="" factors="" family="" for="" found="" free="" frequency="" frequent="" from="" genetic="" geographic="" greater="" groups="" haplotype="" harvest.="" have="" herd="" home="" hunter="" i.e.="" ideal="" identified="" illinois="" immunity="" in="" increase="" increasing="" indication="" individually="" infected="" infection="" inheritance="" is="" less="" likelihood="" likely="" locations="" low="" management="" match="" matched-case="" may="" minimize="" more="" multiple="" nature="" negative="" nonetheless="" not="" obtainable="" of="" on="" one="" or="" origin="" originating="" other="" outside="" over="" paired-case="" paired="" perfectly="" play="" population-level="" positive="" possible="" potential="" prnp="" randomly="" range="" ranging="" relatedness="" relationship="" resistance="" restricted="" results="" role="" samples="" sampling="" selected="" sequence="" sex="" significant="" similar="" spurious="" statistical="" status="" strong="" studies="" study="" studying="" suggesting="" susceptibility.="" susceptibility="" than="" that="" the="" therefore="" these="" they="" this="" though="" through="" throughout="" time="" to="" under="" use="" vital="" was="" were="" when="" whitetailed="" with="" without="">

 

The PRNP gene is variable within all species with some mutations affecting susceptibility to TSEs.46-48 Scrapie infection in sheep is the classic example of genetic resistance to a prion disease, where individuals with 2 copies of amino acid sequence V136, R154, Q171 are susceptible to scrapie, and those with 2 copies of the sequence A136, R154, R171 are resistant. 36,37 Changes in the protein coding sequence have been shown to affect the ability of pathogenic prions to convert normal prion proteins31; accordingly, many studies have heavily examined the amino acid variations associated with CWD. Synonymous or silent mutations are often overlooked, but may have a greater effect on protein expression and conformation than expected.49-53Other studies have found significant associations between individual synonymous mutations and CWD susceptibility. 10,28 The specific mechanisms involved between nucleotide variation (specifically synonymous mutations) and CWD are not known, but the rate at which PrPC conformations that are more favorable to PrPSC conversion are produced may be slowed by the presence of certain synonymous mutations.51 Due to the low frequency of haplotypes with similar mutations as haplotype C, we cannot accurately conclude whether or not the specific combination of mutations or any one mutation alone is responsible for reduced CWD susceptibility. Nevertheless, haplotype and diplotype analyses provide more insight in gene-disease association than those restricted to alleles and genotypes54 which are unable to detect additive effects.

 

A solid understanding of the genetics of CWD in white-tailed deer is vital to improve management of CWD on the landscape. Most TSEs are found in domestic or captive animals where management of infected individuals is feasible. For example, scrapie infected flocks can be handled through a process generally involving genetic testing, removal and destruction of infected or suspect animals, followed by decontamination of facilities and equipment.55 Containment of free ranging deer in wild populations potentially infected with CWD and decontamination of the environment is not reasonably possible. The long term effects of CWD are not yet known but it is conceivable that an unmanaged infected population would be gradually extirpated as the disease progresses 56,57 or at least reduced to low densities with high disease prevalence.58,59 Either outcome would have severe ecological effects (e.g., deer play a major role in affecting plant communities60 and as a prey source61,62) as well as negative economic impacts to hunting. Overall disease prevalence has remained at relatively low levels in Illinois compared to Wisconsin. 11 It is important to note that at the time of sampling, CWD had been found in 6 Illinois counties and has since been detected in 14.9 Complete eradication of CWD among free ranging white-tailed deer may not be possible; however, an active containment effort in Illinois appears to have prevented significant increases in prevalence.9,11,12 Further examination of PRNP haplotype and diplotype frequencies across northern Illinois and southern Wisconsin in conjunction with population structure and movement45,63,64 will be useful in identifying localities with greater or reduced susceptibility risk. Effectiveness of CWD containment efforts can be aided through genetic testing and redirecting management resources.

 

snip...

 

http://www.tandfonline.com/doi/pdf/10.1080/19336896.2015.1115179

 

 

CWD TESTING

 

Other diagnostic tests and technologies that allow more rapid testing of larger numbers of samples continue to be developed. A rectal associated mucosal lymphoid tissue (RAMALT) biopsy (live-animal) test has been developed by researchers and appears to hold promise for future use in certain CWD monitoring or management situations in farmed cervids. This technique utilizes the current IHC testing technologies described above.

 

*** The RAMALT is not currently approved as an official test for CWD.

 

https://www.aphis.usda.gov/aphis/ourfocus/animalhealth/animal-disease-information/sa_alternate_livestock/sa_cervid_health/sa_cwd/ct_diagnostics

 

Seeded amplification of chronic wasting disease prions in nasal brushings and recto-anal mucosa associated lymphoid tissues from elk by real time quaking-induced conversion

 

Nicholas J. Haley#,a, Chris Siepkera, Laura L. Hoon-Hanksb, Gordon Mitchellc, W. David Walterd, Matteo Mancae, Ryan J. Monellof, Jenny G. Powersf, Margaret A. Wildf, Edward A. Hooverb, Byron Caugheye and Jürgen A. Richta + Author Affiliations

 

Department of Diagnostic Medicine and Pathobiology, College of Veterinary Medicine, Kansas State University (KSU), Manhattan, KS, USAa Department of Microbiology, Immunology and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, USAb Canadian Food Inspection Agency, National and OIE Reference Laboratory for Scrapie and CWD, Ottawa Laboratory Fallowfield, Ottawa, ON, Canadac U.S. Geological Survey, Pennsylvania Cooperative Fish and Wildlife Research Unit, The Pennsylvania State University, University Park, PA, USAd TSE/Prion Biochemistry Section, Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories (RML), National Institute of Allergy and Infectious Diseases, Hamilton, MT, USAe National Park Service, Biological Resources Division, 1201 Oak Ridge Drive, Suite 200, Fort Collins, Colorado 80525, USAf

 

ABSTRACT

 

Chronic wasting disease (CWD), a transmissible spongiform encephalopathy of cervids, was first documented nearly fifty years ago in Colorado and Wyoming, and has since been detected across North America and to the Republic of Korea. The expansion of this disease makes the development of sensitive diagnostic assays and antemortem sampling techniques crucial for the mitigation of spread; this is especially true in cases of relocation/reintroduction, or prevalence studies in large or protected herds where depopulation may be contraindicated. This study sought to evaluate the sensitivity of the real-time quaking-induced conversion (RT-QuIC) assay in recto-anal mucosa associated lymphoid tissue (RAMALT) biopsies and nasal brushings collected antemortem. These findings were compared to results from ante- and postmortem samples evaluated using immunohistochemistry (IHC). RAMALT samples were collected from populations of farmed and free-ranging Rocky Mountain elk (Cervus elaphus nelsoni, n=323), with nasal brushes collected from a subpopulation of these animals (n=205). We hypothesized the sensitivity of RT-QuIC would be comparable to IHC in RAMALT, and would correspond to IHC of postmortem tissues. We found RAMALT sensitivity (77.3%) to be highly correlative between RT-QuIC and IHC. Sensitivity was lower when testing nasal brushings (34%), though both RAMALT and nasal brush sensitivities were dependent on both PRNP genotype and disease progression determined by obex score. These data suggest that RT-QuIC, like IHC, is a relatively sensitive assay for detection of CWD prions in RAMALT biopsies, and with further investigation has potential for large scale and rapid automated testing for CWD in antemortem samples.

 

FOOTNOTES

 

↵#Corresponding author (e-mail: nicholas.j.haley@gmail.com) Copyright © 2016, American Society for Microbiology. All Rights Reserved. http://jcm.asm.org/content/early/2016/02/11/JCM.02700-15.abstract

 

Saturday, February 20, 2016

 

Seeded amplification of chronic wasting disease prions in nasal brushings and recto-anal mucosa associated lymphoid tissues from elk by real time quaking-induced conversion

 

http://chronic-wasting-disease.blogspot.com/2016/02/seeded-amplification-of-chronic-wasting.html

 

Sunday, February 14, 2016

 

Antemortem detection of chronic wasting disease prions in nasal brush collections and rectal biopsies from white-tailed deer by real time quaking-induced conversion

 

http://chronic-wasting-disease.blogspot.com/2016/02/antemortem-detection-of-chronic-wasting.html

 

Research Project: TRANSMISSION, DIFFERENTIATION, AND PATHOBIOLOGY OF TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES

 

Title: Antemortem detection of chronic wasting disease prions in nasal brush collections and rectal biopsies from white-tailed deer by real time quaking-induced conversion

 

Authors

 

item Haley, Nicholas - item Siepker, Chris - item Walter, W. David - item Thomsen, Bruce - item Greenlee, Justin item Lehmkuhl, Aaron - item Richt, Jürgen -

 

Submitted to: Journal of Clinical Microbiology Publication Type: Peer Reviewed Journal Publication Acceptance Date: November 27, 2015 Publication Date: February 10, 2016 Citation: Haley, N.J., Siepker, C., Walter, W.D., Thomsen, B.V., Greenlee, J.J., Lehmkuhl, A.D., Richt, J.A. 2016. Antemortem detection of chronic wasting disease prions in nasal brush collections and rectal biopsy specimens from white-tailed deer by real time quaking-induced conversion. Journal of Clinical Microbiology. 54(4):1108-1116.

 

Interpretive Summary: Chronic Wasting Disease (CWD), a fatal neurodegenerative disease that occurs in farmed and wild cervids (deer and elk) of North America, is a transmissible spongiform encephalopathy (TSE). TSEs are caused by infectious proteins called prions that are resistant to various methods of decontamination and environmental degradation. Early diagnosis of CWD in wild and captive herds would be very helpful to controlling the spread of CWD, for which there are not yet any preventative or treatment measures available. The purpose of this study was to test a laboratory method of prion detection (real-time Quaking Induced Conversion; RT-QuIC) that has the potential to detect very low levels of infectious prions in samples collected from live animals against the gold standard diagnostic where abnormal prion in tissues is stained on a microscope slide. This study reports that RT-QuIC detects more cases of CWD than standard methods, but also can identify a small number of animals without CWD as being positive. In the case of CWD, where it is likely that large numbers of animals within a herd may be positive, misidentifying a negative as a positive may have less of an impact than in the case of other prion diseases such as bovine spongiform encephalopathy considering that this test allows testing much larger numbers of samples with a faster turn around time than traditional methods. This information could have an impact on regulatory and wildlife officials developing plans to reduce or eliminate CWD and cervid farmers that want to ensure that their herd remains CWD-free.

 

Technical Abstract: Chronic wasting disease (CWD), a transmissible spongiform encephalopathy of cervids, was first documented nearly fifty years ago in Colorado and Wyoming and has since spread to cervids in 23 states, 2 Canadian provinces, and the Republic of Korea. The increasing expansion of this disease makes the development of sensitive diagnostic assays and antemortem sampling techniques crucial for the mitigation of spread; this is especially true in cases of relocation/reintroduction of farmed or free-ranging deer and elk, or surveillance studies in private or protected herds where depopulation may be contraindicated. This study sought to evaluate the sensitivity of the real-time quaking-induced conversion (RT-QuIC) assay in samples collected antemortem. Antemortem findings were then compared to results from ante- and postmortem samples evaluated using the current gold standard diagnostic assay, immunohistochemistry (IHC). Recto-anal mucosal associated lymphoid tissue (RAMALT) biopsies and nasal brush collections from three separate herds of farmed white-tailed deer (n=409) were evaluated, along with standard postmortem microscopic analysis of brainstem at the level of the obex and retropharyngeal lymph nodes. We hypothesized the sensitivity of RT-QuIC would be comparable to IHC in antemortem tissues, and would correlate with both genotype and stage of clinical disease. Our results showed that RAMALT testing by RT-QuIC had the highest sensitivity (69.8%) when compared to postmortem testing. This data suggests that RT-QuIC, like IHC, is a fairly sensitive assay for detection of CWD prions in rectal biopsies and other antemortem samples, and with further investigation has potential for large scale and rapid automated testing for CWD diagnosis.

 

http://www.ars.usda.gov/research/publications/publications.htm?seq_no_115=320291

 

Research Project: TRANSMISSION, DIFFERENTIATION, AND PATHOBIOLOGY OF TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES

 

Title: Clinical stage of infection is critical in the antemortem diagnosis of chronic wasting disease in deer and elk

 

Authors

 

item Siepker, Chris - item Haley, Nicholas - item Walter, W. David - item Hoon-Hanks, Laura - item Monello, Ryan - item Powers, Jenny - item Greenlee, Justin item Thomsen, Bruce - item Lehmkuhl, Aaron - item Mitchell, Gordon - item Nichols, Tracy - item Hoover, Edward - item Richt, Juergen -

 

Submitted to: Prion Publication Type: Abstract Only Publication Acceptance Date: March 5, 2015 Publication Date: N/A

 

Technical Abstract: Chronic wasting disease (CWD) is an efficiently transmitted spongiform encephalopathy of cervids (e.g. deer, elk, and moose), and is the only known prion disease affecting both free-ranging wildlife and captive animals. The antemortem detection of CWD and other prion diseases has proven difficult, due in part to difficulties in identifying an appropriate peripheral tissue specimen and complications with conventional test sensitivity. At present, biopsies of the recto-anal mucosal-associated lymphoid tissues (RAMALT) have shown promising sensitivity and are practical to collect in live animals. Nasal brush collections have likewise proven both sensitive and practical for identification of prion infections in humans. In this study, we evaluated both RAMALT and nasal brush collections by real time quaking-induced conversion (RT-QuIC), and compared our findings to RAMALT immunohistochemistry as well as conventional postmortem evaluation of obex and retropharyngeal lymph node tissues from over 700 captive and free-ranging deer and elk in areas with endemic CWD. We correlated our results with various clinical findings, including pathological stage of infection as determined by obex scoring, PrP genotype, age, and sex. While the sensitivity of RAMALT RT-QuIC analyses exceeded that of RAMALT IHC (69-80% vs. >44%) and nasal brush collections (15-30%), the sensitivity of both biopsy and nasal brush analyses were dependent primarily on clinical stage of disease, although PrP genotype was also an important predictor of sample positivity. ***Our findings further demonstrate the potential and limitations of antemortem sample analyses by RT-QuIC in the identification and management of prion diseases.

 

http://www.ars.usda.gov/research/publications/publications.htm?SEQ_NO_115=314836

 

*** CHRONIC WASTING DISEASE TESTING PROTOCAL FOR WILD CERVIDAE proposing the United States Animal Health Association (USAHA) urge the USDA to amend CFR 81.3 ***

 

Committee Business:

 

One resolution was proposed by a committee member titled CHRONIC WASTING DISEASE TESTING PROTOCAL FOR WILD CERVIDAE proposing the United States Animal Health Association (USAHA) urge the USDA to amend CFR 81.3 (b); proposing wild cervids captured for interstate movement and release, have two forms of identification, one of which that is official identification, must be PrP genotyped for Chronic Wasting Disease resistance, tested for Chronic Wasting Disease using a rectal biopsy test. The committee discussed and debated the terms and science related to this resolution proposal including that currently there is no science indicating there are “genotype resistant” cervids to acquiring the CWD prion. The term “resistant” is miss-leading. There are only different cervid genotypes that acquire the infectious prions at different rates and show clinical signs at variable rates, some at prolonged periods after acquiring the prion or they are slow to accumulate detectable levels.. Since all infected animals would be presumed to be capable of shedding the prions into the environment, genotypes with clinical “resistance” or prolonged indication of clinical presentation of the disease, may well potentially be considered prolonged shedders of the prion. Additionally there was discussion put forth by several committee members concerning the lack of regulatory validation of the rectal biopsy test. Also, the test can only be used on young animals and there I significant test sensitivity and specificity variability between cervid species when using this test. A new motion to the proposed resolution was to table this resolution, reword the resolution potentially to be a recommendation for USDA to provide a guidance document to the states for surveillance of CWD on interstate translocations od wild cervids. It was proposed that this new resolution/recommendation be discussed during the Farmed Cervid Subcommittee and forward then to the Captive Wildlfie and Alternative Livestock committee. The motion was proposed by member Charlie Seale and seconded by member Sean Shaffer which was passed by committee. The Committee on Wildlife Diseases adjourned at 515 PM.

 

http://www.usaha.org/Portals/6/Reports/2015/report-wd-2015.pdf

 

Tuesday, September 22, 2015

 

*** Host Determinants of Prion Strain Diversity Independent of Prion Protein Genotype

 

http://transmissiblespongiformencephalopathy.blogspot.com/2015/09/host-determinants-of-prion-strain.html

 

Friday, August 28, 2015

 

*** Chronic Wasting Disease CWD TSE Prion Diagnostics and subclinical infection

 

http://chronic-wasting-disease.blogspot.com/2015/08/chronic-wasting-disease-cwd-tse-prion.html

 

Monday, July 18, 2016

 

Texas Parks Wildlife Dept TPWD HIDING TSE (CWD) in Deer Herds, Farmers Sampling Own Herds, Rapid Testing, False Negatives, a Recipe for Disaster

 

http://chronic-wasting-disease.blogspot.com/2016/07/texas-parks-wildlife-dept-tpwd-hiding.html

Tuesday, August 02, 2016

 

Chronic wasting disease of deer – is the battle to keep Europe free already lost?

 

http://chronic-wasting-disease.blogspot.com/2016/08/chronic-wasting-disease-of-deer-is.html

 

Tuesday, April 12, 2016

 

The first detection of Chronic Wasting Disease (CWD) in Europe free-ranging reindeer from the Nordfjella population in South-Norway.

 

http://chronic-wasting-disease.blogspot.com/2016/04/the-first-detection-of-chronic-wasting.html

 

Tuesday, June 14, 2016

 

*** Chronic Wasting Disease (CWD) in a moose from Selbu in Sør-Trøndelag Norway ***

 

http://chronic-wasting-disease.blogspot.com/2016/06/chronic-wasting-disease-cwd-in-moose.html

 

Thursday, July 07, 2016

 

Norway reports a third case Chronic Wasting Disease CWD TSE Prion in 2nd Norwegian moose

 

14/06/2016 - Norway reports a third case

 

http://chronic-wasting-disease.blogspot.com/2016/07/norway-reports-third-case-chronic.html

 

Saturday, July 16, 2016

 

Chronic wasting Disease in Deer (CWD or Spongiform Encephalopathy) The British Deer Society 07/04/2016

 

Red Deer Ataxia or Chronic Wasting Disease CWD TSE PRION?

 

could this have been cwd in the UK back in 1970’S ???

 

http://collections.europarchive.org/tna/20090505194948/http://bseinquiry.gov.uk/files/yb/1982/07/05001001.pdf

 

http://collections.europarchive.org/tna/20090505194948/http://bseinquiry.gov.uk/files/yb/1982/07/28001001.pdf

 

http://collections.europarchive.org/tna/20090505194948/http://bseinquiry.gov.uk/files/yb/1983/03/01001001.pdf

 

http://www.tandfonline.com/doi/pdf/10.1080/00480169.1979.34665

 

SEE FULL TEXT ;

 

http://chronic-wasting-disease.blogspot.com/2016/07/chronic-wasting-disease-in-deer-cwd-or.html

 

Wednesday, August 10, 2016

 

Arkansas Chronic Wasting Disease CWD TSE Prion Potentially Trucked in from Missouri, what about Florida and ?

 

http://chronic-wasting-disease.blogspot.com/2016/08/arkansas-chronic-wasting-disease-cwd.html

 

Wednesday, July 27, 2016

 

Arkansas CWD 101 positive cases documented to date, Biologists to take additional samples in in southern Pope County, Aug. 1-5

 

http://chronic-wasting-disease.blogspot.com/2016/07/arkansas-cwd-101-positive-cases.html

 

Saturday, July 09, 2016

 

Texas Intrastate – within state movement of all Cervid or Trucking Chronic Wasting Disease CWD TSE Prion Moratorium

 

http://chronic-wasting-disease.blogspot.com/2016/07/texas-intrastate-within-state-movement.html

 

Friday, July 01, 2016

 

*** TEXAS Thirteen new cases of chronic wasting disease (CWD) were confirmed at a Medina County captive white-tailed deer breeding facility on June 29, 2016***

 

http://chronic-wasting-disease.blogspot.com/2016/07/texas-thirteen-new-cases-of-chronic.html

 

Tuesday, August 02, 2016

 

TEXAS TPWD Sets Public Hearings on Deer Movement Rule Proposals in Areas with CWD Rule Terry S. Singeltary Sr. comment submission

 

http://chronic-wasting-disease.blogspot.com/2016/08/texas-tpwd-sets-public-hearings-on-deer.html

 

Friday, July 29, 2016

 

IOWA CHRONIC WASTING DISEASE CWD TSE PRION TOTAL TO DATE 304 CASES WILD AND CAPTIVE REPORT UPDATE JULY 2016

 

http://chronic-wasting-disease.blogspot.com/2016/07/iowa-chronic-wasting-disease-cwd-tse.html

 

Friday, August 05, 2016

 

MINNESOTA CHRONIC WASTING DISEASE SURVEILLANCE AND TESTING CWD TSE PRION UPDATE

 

http://chronic-wasting-disease.blogspot.com/2016/08/minnesota-chronic-wasting-disease.html

 

Monday, August 01, 2016

 

Florida Fish and Wildlife Conservation Commission CWD TSE Prion Surveillance Monitoring Programs and Testing

 

http://chronic-wasting-disease.blogspot.com/2016/08/florida-fish-and-wildlife-conservation.html

 

Tuesday, July 19, 2016

 

MONTANA CHRONIC WASTING DISEASE CWD TSE PRION UPDATE STILL SHOWS ONLY 9 CAPTIVE CASES CONFIRMED FROM Philipsburg Kesler Game game since 1999

 

http://chronic-wasting-disease.blogspot.com/2016/07/montana-chronic-wasting-disease-cwd-tse.html

 

Sunday, July 17, 2016

 

Virginia Chronic Wasting Disease CWD As of March 2016 has diagnosed 13 CWD-positive white-tailed deer

 

http://chronic-wasting-disease.blogspot.com/2016/07/virginia-chronic-wasting-disease-cwd-as.html

 

Sunday, July 17, 2016

 

West Virginia Chronic Wasting Disease CWD has been found in 195 white-tailed deer As of June 2016

 

http://chronic-wasting-disease.blogspot.com/2016/07/west-virginia-chronic-wasting-disease.html

 

Sunday, May 08, 2016

 

WISCONSIN CHRONIC WASTING DISEASE CWD TSE PRION SPIRALING FURTHER INTO THE ABYSS UPDATE

 

http://chronic-wasting-disease.blogspot.com/2016/05/wisconsin-chronic-wasting-disease-cwd.html

 

Tuesday, March 08, 2016

 

Oklahoma Chronic Wasting Disease CWD of Deer and Elk Surveillance, Testing, and Preparedness

 

http://chronic-wasting-disease.blogspot.com/2016/03/oklahoma-chronic-wasting-disease-cwd-of.html

 

Wednesday, April 27, 2016

 

WYOMING GAME AND FISH DEPARTMENT CHRONIC WASTING DISEASE MANAGEMENT PLAN APRIL 22, 2016

 

http://chronic-wasting-disease.blogspot.com/2016/04/wyoming-game-and-fish-department.html

 

Sunday, July 17, 2016

 

*** CHRONIC WASTING DISEASE CWD TSE PRION GLOBAL REPORT UPDATE JULY 17 2016 ***

 

http://chronic-wasting-disease.blogspot.com/2016/07/chronic-wasting-disease-cwd-tse-prion.html

 

Friday, February 05, 2016

 

*** Report of the Committee on Wildlife Diseases FY2015 CWD TSE PRION Detections in Farmed Cervids and Wild ***

 

http://chronic-wasting-disease.blogspot.com/2016/02/report-of-committee-on-wildlife.html

 

Friday, August 14, 2015

 

*** Susceptibility of cattle to the agent of chronic wasting disease from elk after intracranial inoculation ***

 

http://chronic-wasting-disease.blogspot.com/2015/08/susceptibility-of-cattle-to-agent-of.html

 

Chronic Wasting Disease Susceptibility of Four North American Rodents

 

Chad J. Johnson1*, Jay R. Schneider2, Christopher J. Johnson2, Natalie A. Mickelsen2, Julia A. Langenberg3, Philip N. Bochsler4, Delwyn P. Keane4, Daniel J. Barr4, and Dennis M. Heisey2 1University of Wisconsin School of Veterinary Medicine, Department of Comparative Biosciences, 1656 Linden Drive, Madison WI 53706, USA 2US Geological Survey, National Wildlife Health Center, 6006 Schroeder Road, Madison WI 53711, USA 3Wisconsin Department of Natural Resources, 101 South Webster Street, Madison WI 53703, USA 4Wisconsin Veterinary Diagnostic Lab, 445 Easterday Lane, Madison WI 53706, USA *Corresponding author email: cjohnson@svm.vetmed.wisc.edu

 

We intracerebrally challenged four species of native North American rodents that inhabit locations undergoing cervid chronic wasting disease (CWD) epidemics. The species were: deer mice (Peromyscus maniculatus), white-footed mice (P. leucopus), meadow voles (Microtus pennsylvanicus), and red-backed voles (Myodes gapperi). The inocula were prepared from the brains of hunter-harvested white-tailed deer from Wisconsin that tested positive for CWD. Meadow voles proved to be most susceptible, with a median incubation period of 272 days. Immunoblotting and immunohistochemistry confirmed the presence of PrPd in the brains of all challenged meadow voles. Subsequent passages in meadow voles lead to a significant reduction in incubation period. The disease progression in red-backed voles, which are very closely related to the European bank vole (M. glareolus) which have been demonstrated to be sensitive to a number of TSEs, was slower than in meadow voles with a median incubation period of 351 days. We sequenced the meadow vole and red-backed vole Prnp genes and found three amino acid (AA) differences outside of the signal and GPI anchor sequences. Of these differences (T56-, G90S, S170N; read-backed vole:meadow vole), S170N is particularly intriguing due its postulated involvement in "rigid loop" structure and CWD susceptibility. Deer mice did not exhibit disease signs until nearly 1.5 years post-inoculation, but appear to be exhibiting a high degree of disease penetrance. White-footed mice have an even longer incubation period but are also showing high penetrance. Second passage experiments show significant shortening of incubation periods. Meadow voles in particular appear to be interesting lab models for CWD. These rodents scavenge carrion, and are an important food source for many predator species. Furthermore, these rodents enter human and domestic livestock food chains by accidental inclusion in grain and forage. Further investigation of these species as potential hosts, bridge species, and reservoirs of CWD is required.

 

 http://chronic-wasting-disease.blogspot.com/2009/08/third-international-cwd-symposium-july.html

 

Veterinary Pathology Onlinevet.sagepub.com Published online before print February 27, 2014, doi: 10.1177/0300985814524798 Veterinary Pathology February 27, 2014 0300985814524798

 

Lesion Profiling and Subcellular Prion Localization of Cervid Chronic Wasting Disease in Domestic Cats

 

D. M. Seelig1⇑ A. V. Nalls1 M. Flasik2 V. Frank1 S. Eaton2 C. K. Mathiason1 E. A. Hoover1 1Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, CO, USA 2Department of Biomedical Sciences, Colorado State University, Fort Collins, CO, USA D. M. Seelig, University of Minnesota, Department of Veterinary Clinical Sciences, Room 339 VetMedCtrS, 6192A (Campus Delivery Code), 1352 Boyd Ave, St Paul, MN 55108, USA. Email address: dseelig@umn.edu

 

Abstract

 

Chronic wasting disease (CWD) is an efficiently transmitted, fatal, and progressive prion disease of cervids with an as yet to be fully clarified host range. While outbred domestic cats (Felis catus) have recently been shown to be susceptible to experimental CWD infection, the neuropathologic features of the infection are lacking. Such information is vital to provide diagnostic power in the event of natural interspecies transmission and insights into host and strain interactions in interspecies prion infection. Using light microscopy and immunohistochemistry, we detail the topographic pattern of neural spongiosis (the “lesion profile”) and the distribution of misfolded prion protein in the primary and secondary passage of feline CWD (FelCWD). We also evaluated cellular and subcellular associations between misfolded prion protein (PrPD) and central nervous system neurons and glial cell populations. From these studies, we (1) describe the novel neuropathologic profile of FelCWD, which is distinct from either cervid CWD or feline spongiform encephalopathy (FSE), and (2) provide evidence of serial passage-associated interspecies prion adaptation. In addition, we demonstrate through confocal analysis the successful co-localization of PrPD with neurons, astrocytes, microglia, lysosomes, and synaptophysin, which, in part, implicates each of these in the neuropathology of FelCWD. In conclusion, this work illustrates the simultaneous role of both host and strain in the development of a unique FelCWD neuropathologic profile and that such a profile can be used to discriminate between FelCWD and FSE.

 

prion chronic wasting disease immunohistochemistry interspecies cat feline spongiform encephalopathy transmissible spongiform encephalopathy adaptation species barrier

 

 http://vet.sagepub.com/content/early/2014/02/27/0300985814524798.abstract

 

Monday, August 8, 2011 Susceptibility of Domestic Cats to CWD Infection

 

Oral.29: Susceptibility of Domestic Cats to CWD Infection

 

Amy Nalls, Nicholas J. Haley, Jeanette Hayes-Klug, Kelly Anderson, Davis M. Seelig, Dan S. Bucy, Susan L. Kraft, Edward A. Hoover and Candace K. Mathiason†

 

Colorado State University; Fort Collins, CO USA†Presenting author; Email: ckm@lamar.colostate.edu

 

Domestic and non-domestic cats have been shown to be susceptible to one prion disease, feline spongiform encephalopathy (FSE), thought to be transmitted through consumption of bovine spongiform encephalopathy (BSE) contaminated meat. Because domestic and free ranging felids scavenge cervid carcasses, including those in CWD affected areas, we evaluated the susceptibility of domestic cats to CWD infection experimentally. Groups of n = 5 cats each were inoculated either intracerebrally (IC) or orally (PO) with CWD deer brain homogenate. Between 40–43 months following IC inoculation, two cats developed mild but progressive symptoms including weight loss, anorexia, polydipsia, patterned motor behaviors and ataxia—ultimately mandating euthanasia. Magnetic resonance imaging (MRI) on the brain of one of these animals (vs. two age-matched controls) performed just before euthanasia revealed increased ventricular system volume, more prominent sulci, and T2 hyperintensity deep in the white matter of the frontal hemisphere and in cortical grey distributed through the brain, likely representing inflammation or gliosis. PrPRES and widely distributed peri-neuronal vacuoles were demonstrated in the brains of both animals by immunodetection assays. No clinical signs of TSE have been detected in the remaining primary passage cats after 80 months pi. Feline-adapted CWD was sub-passaged into groups (n=4 or 5) of cats by IC, PO, and IP/SQ routes. Currently, at 22 months pi, all five IC inoculated cats are demonstrating abnormal behavior including increasing aggressiveness, pacing, and hyper responsiveness.

 

*** Two of these cats have developed rear limb ataxia. Although the limited data from this ongoing study must be considered preliminary, they raise the potential for cervid-to-feline transmission in nature.

 

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

 

 http://felinespongiformencephalopathyfse.blogspot.com/2011/08/susceptibility-of-domestic-cats-to-cwd.html

 

AD.63:

 

Susceptibility of domestic cats to chronic wasting disease

 

Amy V.Nalls,1 Candace Mathiason,1 Davis Seelig,2 Susan Kraft,1 Kevin Carnes,1 Kelly Anderson,1 Jeanette Hayes-Klug1 and Edward A. Hoover1 1Colorado State University; Fort Collins, CO USA; 2University of Minnesota; Saint Paul, MN USA

 

Domestic and nondomestic cats have been shown to be susceptible to feline spongiform encephalopathy (FSE), almost certainly caused by consumption of bovine spongiform encephalopathy (BSE)-contaminated meat. Because domestic and free-ranging nondomestic felids scavenge cervid carcasses, including those in areas affected by chronic wasting disease (CWD), we evaluated the susceptibility of the domestic cat (Felis catus) to CWD infection experimentally. Cohorts of 5 cats each were inoculated either intracerebrally (IC) or orally (PO) with CWD-infected deer brain. At 40 and 42 mo post-inoculation, two IC-inoculated cats developed signs consistent with prion disease, including a stilted gait, weight loss, anorexia, polydipsia, patterned motor behaviors, head and tail tremors, and ataxia, and progressed to terminal disease within 5 mo. Brains from these two cats were pooled and inoculated into cohorts of cats by IC, PO, and intraperitoneal and subcutaneous (IP/SC) routes. Upon subpassage, feline-adapted CWD (FelCWD) was transmitted to all IC-inoculated cats with a decreased incubation period of 23 to 27 mo. FelCWD was detected in the brains of all the symptomatic cats by western blotting and immunohistochemistry and abnormalities were seen in magnetic resonance imaging, including multifocal T2 fluid attenuated inversion recovery (FLAIR) signal hyper-intensities, ventricular size increases, prominent sulci, and white matter tract cavitation. Currently, 3 of 4 IP/SQ and 2 of 4 PO inoculared cats have developed abnormal behavior patterns consistent with the early stage of feline CWD.

 

*** These results demonstrate that CWD can be transmitted and adapted to the domestic cat, thus raising the issue of potential cervid-to- feline transmission in nature.

 

http://www.prion2013.ca/tiny_uploads/forms/Scientific-Program.pdf

 

www.landesbioscience.com

 

PO-081: Chronic wasting disease in the cat— Similarities to feline spongiform encephalopathy (FSE)

 

http://www.landesbioscience.com/journals/prion/04-Prion6-2-Pathogenesis-and-pathology.pdf

 

http://chronic-wasting-disease.blogspot.com/2012/05/chronic-wasting-disease-cwd-prion2012.html

 

FELINE SPONGIFORM ENCEPHALOPATHY FSE

 

http://felinespongiformencephalopathyfse.blogspot.com/2009_04_01_archive.html

 

http://felinespongiformencephalopathyfse.blogspot.com/

 

Wednesday, October 17, 2012

 

Prion Remains Infectious after Passage through Digestive System of American Crows (Corvus brachyrhynchos)

 

http://chronic-wasting-disease.blogspot.com/2012/10/prion-remains-infectious-after-passage.html

 

Prion

 

Volume 9, Issue 4, 2015

 

Porcine prion protein amyloid

 

DOI:10.1080/19336896.2015.1065373Per Hammarströma & Sofie Nyströma*

 

pages 266-277

 

Received: 1 Jun 2015 Accepted: 17 Jun 2015 Accepted author version posted online: 28 Jul 2015

 

© 2015 The Author(s). Published with license by Taylor & Francis Group, LLC Additional license information

 

ABSTRACT

 

Mammalian prions are composed of misfolded aggregated prion protein (PrP) with amyloid-like features. Prions are zoonotic disease agents that infect a wide variety of mammalian species including humans. Mammals and by-products thereof which are frequently encountered in daily life are most important for human health. It is established that bovine prions (BSE) can infect humans while there is no such evidence for any other prion susceptible species in the human food chain (sheep, goat, elk, deer) and largely prion resistant species (pig) or susceptible and resistant pets (cat and dogs, respectively). PrPs from these species have been characterized using biochemistry, biophysics and neurobiology. Recently we studied PrPs from several mammals in vitro and found evidence for generic amyloidogenicity as well as cross-seeding fibril formation activity of all PrPs on the human PrP sequence regardless if the original species was resistant or susceptible to prion disease. Porcine PrP amyloidogenicity was among the studied. Experimentally inoculated pigs as well as transgenic mouse lines overexpressing porcine PrP have, in the past, been used to investigate the possibility of prion transmission in pigs. The pig is a species with extraordinarily wide use within human daily life with over a billion pigs harvested for human consumption each year. Here we discuss the possibility that the largely prion disease resistant pig can be a clinically silent carrier of replicating prions.

 

SNIP...

 

CONCLUDING REMARKS Should the topic of porcine PrP amyloid be more of a worry than of mere academic interest? Well perhaps. Prions are particularly insidious pathogens. A recent outbreak of peripheral neuropathy in human, suggests that exposure to aerosolized porcine brain is deleterious for human health.43,44 Aerosolization is a known vector for prions at least under experimental conditions.45-47 where a mere single exposure was enough for transmission in transgenic mice. HuPrP is seedable with BoPrP seeds and even more so with PoPrP seed (Fig. 1), indicating that humans could be infected by porcine APrP prions while neurotoxicity associated with spongiform encephalopathy if such a disease existed is even less clear. Importantly transgenic mice over-expressing PoPrP are susceptible to BSE and BSE passaged through domestic pigs implicating that efficient downstream neurotoxicity pathways in the mouse, a susceptible host for prion disease neurotoxicity is augmenting the TSE phenotype.25,26 Prions in silent carrier hosts can be infectious to a third species. Data from Collinge and coworkers.21 propose that species considered to be prion free may be carriers of replicating prions. Especially this may be of concern for promiscuous prion strains such as BSE.19,48 It is rather established that prions can exist in both replicating and neurotoxic conformations.49,50 and this can alter the way in which new host organisms can react upon cross-species transmission.51 The na€ıve host can either be totally resistant to prion infection as well as remain non-infectious, become a silent non-symptomatic but infectious carrier of disease or be afflicted by disease with short or long incubation time. The host can harbor and/or propagate the donor strain or convert the strain conformation to adapt it to the na€ıve host species. The latter would facilitate infection and shorten the incubation time in a consecutive event of intra-species transmission. It may be advisable to avoid procedures and exposure without proper biosafety precautions as the knowledge of silence carrier species is poor. One case of iatrogenic CJD in recipient of porcine dura mater graft has been reported in the literature.52 The significance of this finding is still unknown. The low public awareness in this matter is exemplified by the practice of using proteolytic peptide mixtures prepared from porcine brains (Cerebrolysin) as a nootropic drug. While Cerebrolysin may be beneficial for treatment of severe diseases such as vascular dementia,53 a long term follow-up of such a product for recreational use is recommended.

 

http://www.tandfonline.com/doi/abs/10.1080/19336896.2015.1065373#.VddYCJWFOt8

 

Friday, August 21, 2015

 

Porcine prion protein amyloid or mad pig disease PSE Porcine Spongiform Encephalopathy ?

 

http://transmissiblespongiformencephalopathy.blogspot.com/2015/08/porcine-prion-protein-amyloid-or-mad.html

 

http://madporcinedisease.blogspot.com/2015/07/porcine-prion-protein-amyloid-or-mad.html

 

*** Docket No. FDA-2003-D-0432 (formerly 03D-0186) Use of Material from Deer and Elk in Animal Feed Singeltary Submission ***

 

https://www.regulations.gov/#!documentDetail;D=FDA-2003-D-0432-0011

 

Transmission of scrapie prions to primate after an extended silent incubation period

 

Emmanuel E. Comoy , Jacqueline Mikol , Sophie Luccantoni-Freire , Evelyne Correia , Nathalie Lescoutra-Etchegaray , Valérie Durand , Capucine Dehen , Olivier Andreoletti , Cristina Casalone , Juergen A. Richt , Justin J. Greenlee , Thierry Baron , Sylvie L. Benestad , Paul Brown & Jean-Philippe Deslys

 

Scientific Reports 5, Article number: 11573 (2015) doi:10.1038/srep11573 Download Citation Epidemiology Neurological manifestations Prion diseases

 

Received:16 February 2015Accepted:28 May 2015

 

SPONTANEOUS ATYPICAL BOVINE SPONGIFORM ENCEPHALOPATHY

 

***Moreover, sporadic disease has never been observed in breeding colonies or primate research laboratories, most notably among hundreds of animals over several decades of study at the National Institutes of Health25, and in nearly twenty older animals continuously housed in our own facility.***

 

http://www.nature.com/articles/srep11573

 

 Tuesday, August 9, 2016

 

Concurrence with OIE Risk Designations for Bovine Spongiform Encephalopathy [Docket No. APHIS-2015-0055]

 

http://bovineprp.blogspot.com/2016/08/concurrence-with-oie-risk-designations.html

 

Saturday, July 23, 2016

 

BOVINE SPONGIFORM ENCEPHALOPATHY BSE TSE PRION SURVEILLANCE, TESTING, AND SRM REMOVAL UNITED STATE OF AMERICA UPDATE JULY 2016

 

http://bovineprp.blogspot.com/2016/07/bovine-spongiform-encephalopathy-bse.html

 

Tuesday, July 26, 2016

 

Atypical Bovine Spongiform Encephalopathy BSE TSE Prion UPDATE JULY 2016

 

http://bse-atypical.blogspot.com/2016/07/atypical-bovine-spongiform.html

 

Saturday, July 16, 2016

 

Importation of Sheep, Goats, and Certain Other Ruminants [Docket No. APHIS-2009-0095]RIN 0579-AD10

 

WITH great disgust and concern, I report to you that the OIE, USDA, APHIS, are working to further legalize the trading of Transmissible Spongiform Encephalopathy TSE Pion disease around the globe.

 

THIS is absolutely insane. it’s USDA INC.

 

http://scrapie-usa.blogspot.com/2016/07/importation-of-sheep-goats-and-certain.html

 

Thursday, August 4, 2016

 

Secretary's Advisory Committee on Animal Health [Docket No. APHIS-2016-0046] TSE PRION DISEASE

 

http://animalhealthreportpriontse.blogspot.com/2016/08/secretarys-advisory-committee-on-animal.html

 

see BSE TSE SRM breaches being served up to humans as appetizers...

 

Monday, June 20, 2016

 

Specified Risk Materials SRMs BSE TSE Prion Program

 

http://specifiedriskmaterial.blogspot.com/2016/06/specified-risk-materials-srms-bse-tse.html

 

Tuesday, July 12, 2016

 

Chronic Wasting Disease CWD, Scrapie, Bovine Spongiform Encephalopathy BSE, TSE, Prion Zoonosis Science History

 

*** see history of NIH may destroy human brain collection ***

 

http://transmissiblespongiformencephalopathy.blogspot.com/2016/07/chronic-wasting-disease-cwd-scrapie.html

 

Thursday, February 25, 2016

 

U.S. Food & Drug Administration (FDA) FDA/CFSAN Cosmetics Update: Cosmetics Program; Import and Domestic and Transmissible Spongiform Encephalopathy TSE Prion Disease Risk Factors

 

***WARNING TO ALL CONSUMERS AND COUNTRIES AROUND THE WORLD***

 

***Note: FDA labs do not conduct BSE analysis and thus no sampling guidance is issued for BSE. ***

 

http://transmissiblespongiformencephalopathy.blogspot.com/2016/02/us-food-drug-administration-fda.html

 

Sunday, July 24, 2016

 

Chronic Wasting Disease Prions in Elk Antler Velvet and Marketing of this Product in Nutritional Supplements for Humans?

 

Research Project: TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES: THE ROLE OF GENETICS, STRAIN VARIATION, AND ENVIRONMENTAL CONTAMINATION IN DISEASE CONTROL

 

http://chronic-wasting-disease.blogspot.com/2016/07/chronic-wasting-disease-prions-in-elk.html

 

Tuesday, August 16, 2016

 

Docket No. FDA-2011-D-0376 Dietary Supplements: New Dietary Ingredient Notifications and Related Issues; Revised Draft Guidance for Industry Singeltary Submission

 

http://creutzfeldt-jakob-disease.blogspot.com/2016/08/docket-no-fda-2011-d-0376-dietary.html

 

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Thursday, August 04, 2016

 

MEETING ON THE FEASIBILITY OF CARRYING OUT EPIDEMIOLOGICAL STUDIES ON CREUTZFELDT JAKOB DISEASE 1978 THE SCRAPIE FILES IN CONFIDENCE CONFIDENTIAL SCJD

 

http://scrapie-usa.blogspot.com/2016/08/meeting-on-feasibility-of-carrying-out.html

 

Spongiform Encephalopathy in Captive Wild ZOO BSE INQUIRY

 

http://collections.europarchive.org/tna/20090505194948/http://bseinquiry.gov.uk/files/mb/m09a/tab03.pdf

 

Evidence That Transmissible Mink Encephalopathy Results from Feeding Infected Cattle

 

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

 

snip...

 

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

 

http://collections.europarchive.org/tna/20090505194948/http://bseinquiry.gov.uk/files/mb/m09/tab05.pdf

 

http://collections.europarchive.org/tna/20090505194948/http://bseinquiry.gov.uk/files/mb/m09a/tab01.pdf

 

http://collections.europarchive.org/tna/20090505194948/http://bseinquiry.gov.uk/files/yb/1987/06/10004001.pdf

 

In Confidence - Perceptions of unconventional slow virus diseases of animals in the USA - APRIL-MAY 1989 - G A H Wells

 

3. Prof. A. Robertson gave a brief account of BSE. The US approach was to accord it a very low profile indeed. Dr. A Thiermann showed the picture in the ''Independent'' with cattle being incinerated and thought this was a fanatical incident to be avoided in the US at all costs. ...

 

http://web.archive.org/web/20060307063531/http://www.bseinquiry.gov.uk/files/mb/m11b/tab01.pdf

 

”The occurrence of CWD must be viewed against the contest of the locations in which it occurred. It was an incidental and unwelcome complication of the respective wildlife research programmes. Despite it’s subsequent recognition as a new disease of cervids, therefore justifying direct investigation, no specific research funding was forthcoming. The USDA veiwed it as a wildlife problem and consequently not their province!” ...page 26.

 

http://collections.europarchive.org/tna/20080102193705/http://www.bseinquiry.gov.uk/files/mb/m11b/tab01.pdf

 

Terry S. Singeltary Sr. Bacliff, Texas USA flounder9@verizon.net