Post by Terry S. Singeltary Sr. on May 31, 2024 11:02:14 GMT -6
Texas Hundreds of deer test positive for CWD on Trophy Ranch
State kills hundreds of deer at North Texas ranch, after years of legal fights
BY EMILY BRINDLEY UPDATED MAY 31, 2024 10:53 AM
In a November legal filing, the state wrote that RW Trophy Ranch “now hosts the worst-ever CWD outbreak in Texas.” In a mid-March filing, the department notified the state Supreme Court that there had been 208 positive CWD cases at the ranch over the previous three years. Parks and Wildlife staff said this week that the number continued to rise, and reached 254 by Tuesday morning.
www.star-telegram.com/news/state/texas/article288479815.html#storylink=cpy
Texas TAHC TPWD Confirm 132 More Cases of CWD TSE PrP
Jumps from 663 in March, to 795 Positive In May 2024, wow!
tpwd.texas.gov/huntwild/wild/diseases/cwd/positive-cases/listing-cwd-cases-texas.phtml#texasCWD
Listing of CWD Cases in Texas
Show entries
Positive Number CWD Positive Confirmation Date Free Range Captive County Source Species Sex Age
795 2024-05-16 White-tailed Deer Hunt Facility #9 White-tailed Deer - Breeder Deer F 2.9
794 2024-05-16 White-tailed Deer Hunt Facility #9 White-tailed Deer - Breeder Deer F 2.9
793 2024-05-16 White-tailed Deer Hunt Facility #9 White-tailed Deer - Breeder Deer F 2.9
792 2024-05-16 White-tailed Deer Hunt Facility #9 White-tailed Deer - Breeder Deer F 4.8
791 2024-05-16 White-tailed Deer Hunt Facility #9 White-tailed Deer - Breeder Deer F 6.8
790 2024-05-16 White-tailed Deer Hunt Facility #9 White-tailed Deer - Breeder Deer M 3.8
789 2024-05-16 White-tailed Deer Hunt Facility #9 White-tailed Deer - Breeder Deer M 1.8
788 2024-05-16 White-tailed Deer Hunt Facility #9 White-tailed Deer - Breeder Deer M 2.9
787 2024-05-01 White-tailed Deer Frio Facility #21 White-tailed Deer - Breeder Deer F 4.7
786 2024-05-01 White-tailed Deer Frio Facility #21 White-tailed Deer - Breeder Deer M 2.7
785 2024-05-01 White-tailed Deer Frio Facility #21 White-tailed Deer - Breeder Deer F 4.7
784 2024-05-01 White-tailed Deer Frio Facility #21 White-tailed Deer - Breeder Deer M 2.7
783 2024-05-01 White-tailed Deer Frio Facility #21 White-tailed Deer - Breeder Deer M 2.7
782 2024-05-01 White-tailed Deer Frio Facility #21 White-tailed Deer - Breeder Deer M 1.7
781 2024-05-01 White-tailed Deer Frio Facility #21 White-tailed Deer - Breeder Deer M 2.7
780 2024-05-01 White-tailed Deer Frio Facility #21 White-tailed Deer - Breeder Deer M 2.7
779 2024-05-01 White-tailed Deer Frio Facility #21 White-tailed Deer - Breeder Deer M 2.7
778 2024-05-01 White-tailed Deer Frio Facility #21 White-tailed Deer - Breeder Deer M 3.7
777 2024-05-01 White-tailed Deer Frio Facility #21 White-tailed Deer - Breeder Deer M 2.7
776 2024-05-01 White-tailed Deer Zavala Facility #17 White-tailed Deer - Breeder Deer F 8.8
775 2024-05-01 White-tailed Deer Zavala Facility #17 White-tailed Deer - Breeder Deer F 2.8
774 2024-05-01 White-tailed Deer Zavala Facility #17 White-tailed Deer - Breeder Deer F 2.8
773 2024-05-01 White-tailed Deer Zavala Facility #17 White-tailed Deer - Breeder Deer F 6.8
772 2024-05-01 White-tailed Deer Zavala Facility #17 White-tailed Deer - Breeder Deer F 14.8
Showing 1 to 24 of 795 entries
*CWD Positive Confirmation Dates marked with * are dates confirmed by Texas A&M Veterinary Diagnostic Laboratory rather than the National Veterinary Diagnostic Laboratory.
tpwd.texas.gov/huntwild/wild/diseases/cwd/positive-cases/listing-cwd-cases-texas.phtml#texasCWD
THURSDAY, MAY 30, 2024
Texas TAHC TPWD Confirm 132 More Cases of CWD TSE PrP 795 Positive To Date
chronic-wasting-disease.blogspot.com/2024/05/texas-tahc-tpwd-confirm-132-more-cases.html
THURSDAY, MARCH 07, 2024
Texas TPWD CWD Cases Jump to 663 Confirmed To Date
chronic-wasting-disease.blogspot.com/2024/03/texas-tpwd-cwd-cases-jump-to-663.html
those zombie looking deer, well that's a very misleading title to call chronic wasting disease cwd tse prion of cervid, because a perfectly healthy looking deer can have chronic wasting disease cwd tse prion, and be just as deadly.
why is this so stupid, oh, let me count the ways...terry
Diagnosis of preclinical CWD in farmed white-tailed deer in Canada by the immunohistochemical examination of recto-anal mucosa- associated lymphoid tissue (RAMALT)
''The apparent prevalence of disease in these two farms was 21% and 31%.''
“None of these deer were demonstrating signs consistent with CWD.”
www.ars.usda.gov/research/publications/publication/?seqNo115=244240
''The apparent prevalence of disease in these two farms was 21% and 31%.''
'This report summarizes the comparative diagnostic performance of postmortem rectoanal mucosa-associated lymphoid tissue (RAMALT) sampling in two white-tailed deer farms from Saskatchewan, Canada. The apparent prevalence of disease in these two farms was 21% and 31%.'' Title: Diagnosis of preclinical CWD in farmed white-tailed deer in Canada by the immunohistochemical examination of recto-anal mucosa- associated lymphoid tissue (RAMALT)
Author BALACHANDRAN, ARU - Canadian Food Inspection Agency THOMSEN, BRUCE - Animal And Plant Health Inspection Service (APHIS) GIDLEWSKI, THOMAS - Animal And Plant Health Inspection Service (APHIS) SPRAKER, TERRY - Colorado State University MITCHELL, G - Canadian Food Inspection Agency SOUTYRINE, ANDREI - Canadian Food Inspection Agency HARRINGTON, NOEL - Canadian Food Inspection Agency MUNGER, RANDY - Animal And Plant Health Inspection Service (APHIS) Schneider, David O'Rourke, Katherine
Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: 9/12/2009
Publication Date: 9/22/2009
Citation: Balachandran, A., Thomsen, B.V., Gidlewski, T., Spraker, T.R., Mitchell, G., Soutyrine, A., Harrington, N.P., Munger, R., Schneider, D.A., Orourke, K.I. 2009.
Diagnosis of preclinical CWD in farmed white-tailed deer in Canada by the immunohistochemical examination of recto-anal mucosa- associated lymphoid tissue (RAMALT).
NeuroPrion Workshop: New developments in TSEs of domestic and wild animals. pg.9
Interpretive Summary: Diagnosis of prion disease [for example, scrapie in sheep and chronic wasting disease (CWD) in elk and deer] relies upon sensitive detection of disease-associated prion protein in the brain or tissues containing lymph follicles. Live animal testing for scrapie disease in sheep has included evaluation of biopsy samples of the tonsil, third eyelid and rectal mucosa. Similarly, diagnosis of CWD in live elk has been recently accomplished through biopsy of the rectal mucosa. This invited report to the annual NeuroPrion meeting summarizes the diagnostic performance (test sensitivity) of various tissue sampling sites that were collected after death. The report summarizes the findings from two different populations of captive white-tailed deer from Saskatchewan, Canada. The diagnostic performance of the rectal mucosa samples were similar but lower than that achieved in two other lymphoid tissues, but greater than that achieved in the brain. While these studies were conducted on tissues collected after death, the findings demonstrate the comparative potential for biopsy of the rectal mucosa in live deer not yet showing signs of disease. While many factors may influence test performance in other deer populations, these studies showed that false-negative diagnosis occurred most often in deer presumed to be in an early stage of disease and carrying a mutation in the prion protein gene (codon 96).
Technical Abstract: This report summarizes the comparative diagnostic performance of postmortem rectoanal mucosa-associated lymphoid tissue (RAMALT) sampling in two white-tailed deer farms from Saskatchewan, Canada. The apparent prevalence of disease in these two farms was 21% and 31%. None of these deer were demonstrating signs consistent with CWD. The overall tissue-specific test sensitivities were ranked: RPLN>tonsil>RAMALT>obex. Test sensitivities in deer having at least one PRNP G96S allele were generally lower but similarly ranked. False negative RAMALT results were associated with early disease progression, as assessed by PrPCWD accumulation scores in the obex, and/or the PRNP G96S allele. The proportion of CWD-positive RAMALT follicles were generally lowest in deer early in disease progression and/or heterozygous at PRNP codon 96. And, as expected, variation in the proportion CWD-positive RAMALT follicles was inversely related to the total number of observable follicles per sample. These comparisons made on samples collected postmortem suggest general diagnostic evaluation of RAMALT samples in white-tailed deer would have intermediate test sensitivity as compared to evaluation of RPLN and obex. While many factors may influence actual test performance, early stage of disease progression and the PRNP G96S allele are two that were associated with lower test sensitivities.
www.ars.usda.gov/research/publications/publication/?seqNo115=244240
Texas Kimble County Farm Chronic Wasting Disease CWD TSE Prion Approximate Herd Prevalence 12%
SUMMARY MINUTES OF THE 407th COMMISSION MEETING Texas Animal Health Commission
September 22, 2020
Chronic Wasting Disease (CWD):
A new CWD positive breeding herd was disclosed in February 2020 in Kimble County. This herd depopulation was completed in July 2020. Including the two index positive deer, an additional eight more positive deer were disclosed (approximate herd prevalence 12%). Since July 2015 and prior to this discovery, five positive captive breeder herds have been disclosed and four of those are in Medina County. One herd in Lavaca and three herds in Medina County were depopulated leaving one large herd in Medina County that is managed on a herd plan. A new zone was established in Val Verde County in December 2019 as a result of a positive free-ranging White-tailed Deer (WTD). A second positive WTD was also disclosed in February 2020 in the same area.
SUMMARY MINUTES OF THE 407th COMMISSION MEETING – 9/22/2020
Scrapie: The flock identified in April 2016 remains under quarantine in Hartley County.
www.tahc.texas.gov/agency/meetings/minutes/SummaryMinutes_CommMtg_2020-09-22
web.archive.org/web/20201017124040/https://www.tahc.texas.gov/agency/meetings/minutes/SummaryMinutes_CommMtg_2020-09-22.pdf
TEST RESULTS FROM CAPTIVE DEER HERD WITH CHRONIC WASTING DISEASE RELEASED 79.8 percent of the deer tested positive for the disease
DES MOINES – The Iowa Department of Agriculture and Land Stewardship today announced that the test results from the depopulation of a quarantined captive deer herd in north-central Iowa showed that 284 of the 356 deer, or 79.8% of the herd, tested positive for Chronic Wasting Disease (CWD).
web.archive.org/web/20141006172620/http://www.iowaagriculture.gov/press/2014press/press10022014.asp
web.archive.org/web/20140917023729/http://www.iowadnr.gov/Portals/idnr/uploads/Hunting/060613_consent_order.pdf
Wisconsin Buckhorn Flats CWD
SUBJECT: Almond Deer Farm Update
The first case of Chronic Wasting Disease (CWD) among Wisconsin's farm-raised deer occurred in a white-tailed deer buck shot by a hunter at the property (formerly known as Buckhorn Flats) in September 2002. This situation prompted the eventual depopulation of the entire farm.
The deer, a mix of does and yearlings, were destroyed on January 17, 2006- 4 years later- by U.S. Department of Agriculture shooters under a USDA agreement with the farm owner.
Sixty of the 76 animals tested positive for CWD. The 76 deer constituted the breeding herd in the breeding facility on the farm. The property also had a hunting preserve until 2005. Four deer, two does and two fawns, the only deer remaining in the former preserve, were killed and tested as well. CWD was not detected in those animals.
The total number of deer to test positive from this farm from the initial discovery to final depopulation is 82. The nearly 80% prevalence rate discovered on Buckhorn Flats is the highest prevalence recorded in any captive cervid operation in North America.
Tuesday, December 20, 2011
Chronic Wasting Disease CWD WISCONSIN Almond Deer
(Buckhorn Flats) Farm Update DECEMBER 2011 The CWD infection rate was nearly 80%, the highest ever in a North American captive herd. RECOMMENDATION: That the Board approves the purchase of 80 acres of land for $465,000 for the Statewide Wildlife Habitat Program in Portage County and approve the restrictions on public use of the site.
Form 1100-001 (R 2/11) NATURAL RESOURCES BOARD AGENDA ITEM SUBJECT: Information Item: Almond Deer Farm Update FOR:
DECEMBER 2011 BOARD MEETING
TUESDAY TO BE PRESENTED BY TITLE: Tami Ryan, Wildlife Health Section Chief SUMMARY:
dnr.wi.gov/about/nrb/2011/december/12-11-2b2.pdf
web.archive.org/web/20141015022916/http://dnr.wi.gov/about/nrb/2011/december/12-11-2b2.pdf
September 1, 2008
Chronic Wasting Disease in a Wisconsin White-Tailed Deer Farm
Delwyn P. Keane Delwyn.Keane@wvdl.wisc.edu, Daniel J. Barr, […], and Michael D. Samuel+5 View all authors and affiliations Volume 20, Issue 5
doi.org/10.1177/104063870802000534
In September 2002, chronic wasting disease (CWD), a prion disorder of captive and wild cervids, was diagnosed in a white-tailed deer (Odocoileus virginianus) from a captive farm in Wisconsin. The facility was subsequently quarantined, and in January 2006 the remaining 76 deer were depopulated. Sixty animals (79%) were found to be positive by immunohistochemical staining for the abnormal prion protein (PrPCWD)in at least one tissue; the prevalence of positive staining was high even in young deer. Although none of the deer displayed clinical signs suggestive of CWD at depopulation, 49 deer had considerable accumulation of the abnormal prion in the medulla at the level of the obex. Extraneural accumulation of the abnormal protein was observed in 59 deer, with accumulation in the retropharyngeal lymph node in 58of 59 (98%), in the tonsil in 56 of 59 (95%), and in the rectal mucosal lymphoid tissue in 48 of 58 (83%). The retina was positive in 4 deer, all with marked accumulation of prion in the obex. One deer was considered positive for PrPCWD in the brain but not in the extraneural tissue, a novel observation in white-tailed deer. The infection rate in captive deer was 20-fold higher than in wild deer. Although weakly related to infection rates in extraneural tissues, prion genotype was strongly linked to progression of prion accumulation in the obex. Antemortem testing by biopsy of rectoanal mucosal-associated lymphoid tissue (or other peripheral lymphoid tissue) may be a useful adjunct to tonsil biopsy for surveillance in captive herds at risk for CWD infection.
''The facility was subsequently quarantined, and in January 2006 the remaining 76 deer were depopulated. Sixty animals (79%) were found to be positive by immunohistochemical staining for the abnormal prion protein (PrPCWD)in at least one tissue; the prevalence of positive staining was high even in young deer.''
journals.sagepub.com/doi/10.1177/104063870802000534
The infection rates among some captive deer can be much higher, with a rate of 79% (nearly 4 in 5) reported from at least one captive herd.
www.cdc.gov/prions/cwd/occurrence.html
CWD Deer Herd Population Declines
CWD poses a significant threat to the future of hunting in Texas. Deer population declines of 45 and 50 percent have been documented in Colorado and Wyoming. A broad infection of Texas deer populations resulting in similar population impacts would inflict severe economic damage to rural communities and could negatively impact land markets. Specifically, those landowners seeking to establish a thriving herd of deer could avoid buying in areas with confirmed CWD infections. As they do with anthrax-susceptible properties, land brokers may find it advisable to inquire about the status of CWD infections on properties that they present for sale. Prospective buyers should also investigate the status of the wildlife on prospective properties. In addition, existing landowners should monitor developments as TPWD crafts management strategies to identify and contain this deadly disease.
Dr. Gilliland (c-gilliland@tamu.edu) is a research economist with the Texas Real Estate Research Center at Texas A&M University.
www.recenter.tamu.edu/articles/tierra-grande/oh-deer-2314
Colorado CWD TSE Prion Detected in 40 of 54 deer herds, 17 of 42 elk herds, and 2 of 9 moose herds
cpw.state.co.us/Documents/Commission/2022/May/Item.11-PWC_Memo_CWD_Update_EckertMillerWood_April2022-Matthew_Eckert-DNR.pdf
Colorado CWD figures just out; COLORADO CWD UPDATE
Notably, prevalence in the White River herd, one of the state’s largest, rose from 15.3% to 23.6%.
Prevalence increased by about 10%, to 14%, in the Uncompahgre herd, and grew from 3.5% to 8% in the Middle Park herd.
Prevalence fell from 13.6% to 6.7% in the Sweetwater herd and from 12% to 8% in the Big Thompson herd.
Parks and Wildlife has detected the disease in 40 of Colorado’s 54 deer herds, 17 of its 42 elk herds and two of its nine moose herds.
www.gjsentinel.com/news/western_colorado/chronic-wasting-disease-battle-continues/article_3f3e09e2-321a-11ee-a836-bb106b337e90.html
Colorado Chronic Wasting Disease Response Plan December 2018.
Executive Summary Mule deer, white-tailed deer, elk and moose are highly valued species in North America. Some of Colorado’s herds of these species are increasingly becoming infected with chronic wasting disease(CWD).
As of July 2018, at least 31 of Colorado's 54 deer herds (57%), 16 of43 elk herds (37%), and 2 of 9 moose herds (22%) are known to be infected with CWD.
Four of Colorado's 5 largest deer herds and 2 of the state’s 5 largest elk herds are infected.
Deer herds tend to be more heavily infected than elk and moose herds living in the same geographic area.
Not only are the number of infected herds increasing, the past 15 years of disease trends generally show an increase in the proportion of infected animals within herds as well.
Of most concern, greater than a 10-fold increase in CWD prevalence has been estimated in some mule deer herds since the early 2000s; CWD is now adversely affecting the performance of these herds.
snip...(the map on page 71, cwd marked in red, is shocking...tss)
cpw.state.co.us/Documents/RulesRegs/Brochure/BigGame/biggame.pdf
cpw.state.co.us/Documents/Hunting/BigGame/CWD/PDF/ColoradoChronicWastingDiseaseResponsePlan.pdf
Since identifying its first cases of CWD in captive deer in the 70s and finding the first wild infected deer in 1985, Wyoming has seen the disease slowly spread throughout the state. CWD has now been documented in members of the deer family in most of Wyoming’s deer hunting areas, with 20% to 40% percent of mule deer affected in some herds. A 2017 study estimated a 21% annual population decline as a result of the fatal disease.
freerangeamerican.us/chronic-wasting-disease-wyoming/#:~:text=CWD%20has%20now%20been%20documented,result%20of%20the%20fatal%20disease.
How does CWD impact deer, elk, and moose populations?
Recent research in Wyoming has demonstrated declines in both mule and white-tailed deer populations in deer hunt area 65 due to CWD (see below for citations). These declines are in the core endemic area where prevalence is highest. In areas with lower prevalence, effects of CWD are poorly understood but are considered additive along with other factors that can negatively affect deer populations in Wyoming (i.e. habitat loss, predation, other diseases). The distribution and prevalence of CWD in Wyoming elk is less than that of deer. Currently there are no documented direct population impacts in Wyoming elk from CWD; however, research from Rocky Mountain National Park suggests that CWD could impact elk populations at higher prevalence (13%). While CWD has been found in free ranging moose, there have been few detections, and there is no evidence that CWD is currently having an impact on moose populations.
wgfd.wyo.gov/Wildlife-in-Wyoming/More-Wildlife/Wildlife-Disease/Chronic-Wasting-Disease
WYOMING, POWELL — Sobering news resulting from a multi-year Chronic Wasting Disease (CWD) surveillance program by the Wyoming Game and Fish Department between 2018 and 2022 shows significant increases in the fatal disease for the state’s prized mule deer and elk herds.
In one herd, the prevalence rate is calculated at 65% in mule deer bucks, and there are concerning increases in infected elk, including hunt areas popular for Big Horn Basin hunters.
The disease, which typically kills infected animals within two years after initial exposure, now occurs in 34 of Wyoming’s 37 mule deer herds, and 15 of the state’s 36 elk herd units.
www.wyomingnews.com/rocketminer/news/state/cwd-increasing-in-state-deer-elk-herds/article_1005894a-361e-11ee-8900-0743386c0b87.html
Texas CWD Surveillance Positives (cwd totals confirmed at 663 is outdated)
tpwd.texas.gov/huntwild/wild/diseases/cwd/positive-cases/listing-cwd-cases-texas.phtml#texasCWD
Counties where CWD Exposed Deer were Released
tpwd.texas.gov/documents/257/CWD-Trace-OutReleaseSites.pdf
Number of CWD Exposed Deer Released by County
tpwd.texas.gov/documents/258/CWD-Trace-OutReleaseSites-NbrDeer.pdf
Chronic Wasting Disease CWD Captive Herds updated April 2023
www.aphis.usda.gov/aphis/ourfocus/animalhealth/animal-disease-information/cervid/cervids-cwd/cervids-voluntary-hcp
Chronic Wasting Disease CWD Captive Herds updated April 2023
www.aphis.usda.gov/animal_health/animal_diseases/cwd/downloads/status-of-captive-herds.pdf
TPWD Proposed Amendments to Chronic Wasting Disease and canned hunting Mountain lions ban
Proposed Regulations
Learn more and comment online through 5 p.m. May 22, 2024.
As noted previously in this preamble, the department has been engaged in a long-term effort to stem the spread of CWD; however, by 2021 it was apparent that more robust measures were warranted because CWD was still being detected in additional deer breeding facilities, as well as on multiple release sites associated with CWD-positive deer breeding facilities. The commission adopted those rules, which require higher rates of testing, ante-mortem (live-animal) testing of breeder deer prior to release, and enhanced recordkeeping and reporting measures, in December of 2021 (46 TexReg 8724).
Following the implementation of more efficacious testing requirements, an unprecedented increase in CWD detections occurred. Since 2021, CWD has been detected in 22 deer breeding facilities, two release sites associated with CWD-positive deer breeding facilities, and two free-ranging deer in areas where CWD had not been previously detected. Department records indicate that within the last five years those breeding facilities transferred over 7,000 deer to other breeding facilities, release sites, and Deer Management Permit (DMP) sites. All those locations are therefore directly connected to the CWD-positive facilities and are subsequently of epidemiological concern. Additionally, approximately 287 deer breeding facilities received deer from one or more of the directly connected breeding facilities, which means those facilities (referred to as “Tier 1” facilities) are indirectly connected to the positive facilities and are also of epidemiological concern because they have received exposed deer that were in a trace-out breeding facility.
Because of this rapid explosion in epidemiological linkages between deer breeding facilities and associated release sites, the department became concerned about the excessive numbers of deer breeders continuing to be affected by inter-facility transfers, and subsequently determined that additional testing measures could increase the probability of detecting CWD in breeding facilities where it exists before it could be spread to additional breeding facilities and associated release sites.
Learn more and comment online through 5 p.m. May 22, 2024.
tpwd.texas.gov/business/feedback/public_comment/proposals/202405_cwd_rules.phtml
TEXAS BREEDER DEER ESCAPEE WITH CWD IN THE WILD, or so the genetics would show?
OH NO, please tell me i heard this wrong, a potential Texas captive escapee with cwd in the wild, in an area with positive captive cwd herd?
apparently, no ID though. tell me it ain't so please...
23:00 minute mark
''Free Ranging Deer, Dr. Deyoung looked at Genetics of this free ranging deer and what he found was, that the genetics on this deer were more similar to captive deer, than the free ranging population, but he did not see a significant connection to any one captive facility that he analyzed, so we believe, Ahhhhhh, this animal had some captive ahhh, whatnot.''
youtu.be/aoPDeGL6mpQ?t=1384
Commission Agenda Item No. 5 Exhibit B
DISEASE DETECTION AND RESPONSE RULES
PROPOSAL PREAMBLE
1. Introduction.
snip...
A third issue is the accuracy of mortality reporting. Department records indicate that for each of the last five years an average of 26 deer breeders have reported a shared total of 159 escapes. Department records for the same time period indicate an average of 31 breeding facilities reported a shared total of 825 missing deer (deer that department records indicate should be present in the facility, but cannot be located or verified).
tpwd.texas.gov/business/feedback/meetings/2022/1104/agenda/item.phtml?item=5
On January 21, 2017 a tornado took down thousands of feet of fence for a 420-acre illegal deer enclosure in Lamar County that had been subject to federal and state investigation for illegally importing white-tailed deer into Mississippi from Texas (a CWD positive state). Native deer were free to move on and off the property before all of the deer were able to be tested for CWD. Testing will be made available for a period of three years for CWD on the property and will be available for deer killed within a 5-mile radius of the property on a voluntary basis.
www.mdwfp.com/media/254796/2016-17-deer-report.pdf
“It is interesting to note that, in 2001, the State of Texas shifted its deer management strategies toward the same leanings that Kroll has suggested for Wisconsin. In Texas, the change was brought about via heavy lobbying from the high-fence deer ranching industry. This pressure helped convince the Texas Parks and Wildlife to change their regulations and allow private landowners to select the own deer biologists.”
www.texasmonthly.com/story/which-side-fence-are-you
Chronic Wasting Disease in Texas
A Real Disease with Proven Impacts
Produced by a coalition of concerned hunters, landowners, & conservationists (last update 08/2023)
Snip…
Since 2012, CWD has been detected in wild deer in just 7 counties in Texas and is only established in the western panhandle and far west Texas.
In that same period of time, captive deer breeders have exposed almost half of Texas counties to CWD.
Deer held in captive breeding facilities are confined to much tighter spaces, and have intimate contact with many more animals on a daily basis. By far the greatest factor in amplifying the spread of CWD is the artificial movement of these animals, shipped in livestock trailers hundreds of miles, far outside of their natural home range, and ultimately released to co-mingle with wild deer.
Each year, Texas captive deer breeders liberate 20,000-30,000 deer from their pens to the wild.
For every deer breeding facility where a CWD positive deer is discovered, an epidemiological investigation is conducted by the Texas Parks & Wildlife Department and the Texas Animal Health Commission to determine how many other deer may have been exposed to the disease and where they have been shipped. Because of the prolific artificial movement of captive deer, one deer with CWD can impact hundreds of other facilities and ranches across the state.
Unfortunately, released deer in Texas are not required to retain any kind of visible identification (an ear tag), and for this reason, the vast majority of released deer cannot be relocated for testing.
As of August 2023, 116 Texas counties have received possibly infected breeder deer that cannot be located, putting more than 140,000 landowners at risk of the disease.
Snip
The state of Texas has been testing for CWD since 2002. Since that time, more than 302,360 captive and free range deer have been tested.
From 2015-2022, more than 127,000 samples were collected from hunter-harvested and roadkill deer. This sampling rate and risk-based distribution provides scientists confidence that they would have detected the disease if it existed at a very low prevalence (<1%) in any given region at the time sampling began.
Snip…
We have learned from other states where CWD has been present the longest, that a constant increase in the prevalence of the disease may lead to a significant decline in the deer population. When disease prevalence exceeds 20%, deer populations have declined by up to 50%. In some areas of Colorado, where CWD has been present since 1985, mule deer abundance has declined by 45% since that time, despite adequate habitat and no hunting ( Miller et al. 2008 ). Similarly, the South Converse Game Unit in Wyoming has documented CWD prevalence exceeding 50% and has seen an approximate 50% decline in mule deer populations.
Snip…
Rural Economies
Deer hunting is the lifeblood of rural Texas. White-tailed deer hunting is by far the most impactful segment of the hunting economy, representing $4.3 billion, according to a recent Texas A&M Study. And while deer breeders represent a very small segment of that economy (less than 5%), they represent one of the greatest risks. ( Full Texas A&M Report )
Real Estate
Rural land prices are largely driven by recreational buyers with hunting as a top land amenity. Without deer hunting, many of these properties will be worth much less.
Conservation Funding
Deer hunters are the largest funders of wildlife conservation in Texas through excise taxes on firearms, ammunition, and gear along with active membership supporting and funding conservation organizations. If deer hunting suffers due to CWD, all wildlife in Texas lose.
Culture & Health
Texas’ native deer herd has iconic value for all Texans. Deer hunting brings families together, creates camaraderie in communities, and serves to connect Texans to nature. There is no better protein than wild, locally harvested, non-GMO and totally organic venison. A healthy deer herd leads to healthy Texans and a healthy and prosperous Texas.
Snip…
This isn't a disease for our lifetime. It's a disease for our grandchildren's lifetime.
- Dr. Bob Dittmar, Former Texas State Wildlife Veterinarian
Snip…
See the full text with maps, graphs, much more, excellent data…
bit.ly/3xL16Gm
Since 2012, CWD has been detected in wild deer in just 7 counties in Texas and is only established in the western panhandle and far west Texas.
In that same period of time, captive deer breeders have exposed almost half of Texas counties to CWD.
bit.ly/3xL16Gm
As of August 2023, 116 Texas counties have received possibly infected breeder deer that cannot be located, putting more than 140,000 landowners at risk of the disease.
bit.ly/3xL16Gm
ECONOMIC VALUES OF WHITE-TAILED DEER IN TEXAS
2022 SURVEY: PART I
web.archive.org/web/20230809171452/https://nri.tamu.edu/media/3702/economic-values-of-white-tailed-deer-in-texas-2022-survey-part-i.pdf
Don't mess Texas, or with Mother Nature in Texas, but, seems things went terribly wrong down here in Texas with CWD, be careful what you ask for;
TEXAS CWD STRAIN
“Wow,” he said. “Unlike anything we've seen before.”
The disease devastating deer herds may also threaten human health
Scientists are exploring the origins of chronic wasting disease before it becomes truly catastrophic.
Rae Ellen Bichell
Image credit: David Parsons/Istock
April 8, 2019
This story was published in collaboration with the Mountain West News Bureau, a collaboration between Wyoming Public Media, Boise State Public Radio in Idaho, KUER in Salt Lake City and KRCC and KUNC in Colorado.
SNIP...
One day in late February, in their laboratory in Fort Collins, Colorado, Wagner and Zabel compared the prions from the brains of CWD-infected deer in Texas with those of elk in Colorado. They want to know if the proteins were all mangled in the same way, or not. “If they are different, this would suggest that we have different strain properties, which is evidence as we're building our case that we might have multiple strains of CWD circulating in the U.S.,” says Wagner.
Step one is to see if they’re equally easy to destroy using a chemical called guanidine. The shape of a prion dictates everything, including the way it interacts with an animal’s cells and the ease with which chemicals can unfold it.
“Moment of truth,” said Wagner, as she and Zabel huddled around a computer, waiting for results to come through. When they did, Zabel was surprised.
“Wow,” he said. “Unlike anything we've seen before.”
The prions from the Texas deer were a lot harder to destroy than the ones from the Colorado elk. In fact, the guanidine barely damaged them at all. “We’ve never seen that before in any prion strain, which means that it has a completely different structure than we've ever seen before,” says Zabel. And that suggests that it might be a very different kind of chronic wasting disease. The researchers ran the same test on another Texas deer, with the same results.
Now, these are only the preliminary results from a few animals. Wagner and Zabel have a lot more experiments to do. But if future tests come to the same conclusion, it would support their hypothesis that there are multiple strains of chronic wasting disease out there, all with different origins. That, in turn, could mean that this disease will become even trickier to manage than it already is.
And, Zabel adds, there’s something else. “If it's still evolving, it may still evolve into a form that could potentially, eventually affect humans,” he says.
Zabel is not the only one worried about that possibility.
OSTERHOLM, THE EPIDEMIOLOGIST from Minnesota, is also concerned. He directs the Center for Infectious Disease Research and Policy at the University of Minnesota, and is serving a one-year stint as a “Science Envoy for Health Security” with the U.S. State Department. In February, he told Minnesota lawmakers that when it comes to chronic wasting disease, we are playing with fire. “You are going to hear from people that this is not going to be a problem other than a game farm issue. You're going to hear from people that it's not going to transmit to people, and I hope they're right, but I wouldn't bet on it,” he said. “And if we lose this one and haven’t done all we can do, we will pay a price.”
If that wasn’t warning enough, he added: “Just remember what happened in England.”
He was talking about mad cow disease. Decades ago, Osterholm got involved in studying the potential for the newly emerging condition — bovine spongiform encephalopathy, or BSE for short — to be transmitted to humans.
At that point, researchers had yet to document a prion disease in animals that could infect people. They did, however, have a few pieces of the puzzle. For one, work in Papua New Guinea had shown that people could transmit prion diseases to each other if they practiced cannibalism, especially of the brain-eating variety. They also knew that BSE was spreading quickly between cattle. Osterholm says he and others worried that the more widespread it became, the more chances it might have to change into something that could sicken people.
“A lot of people thought that it was an overreaction,” says Osterholm. “Then, of course, in 1996, 10 years later, we recognized that in fact transmission had occurred.” Variant Creutzfeldt-Jakob disease, as the illness is called when it appears in human beings, has infected about 230 people worldwide. Osterholm says he feels like he’s having déjà vu, except that instead of mad cow, now it’s chronic wasting disease that’s spreading in animals, with the potential to cross the species barrier to infect humans.
SNIP...SEE FULL TEXT;
www.hcn.org/articles/wildlife-the-disease-devastating-deer-herds-may-also-threaten-human-health-science
TEXAS CWD STRAIN
77. Assessing chronic wasting disease strain differences in free-ranging cervids across the United States
Kaitlyn M. Wagnera, Caitlin Ott-Connb, Kelly Strakab, Bob Dittmarc, Jasmine Battend, Robyn Piercea, Mercedes Hennessya, Elizabeth Gordona, Brett Israela, Jenn Ballarde and Mark D Zabela
aPrion Research Center at Colorado State University; bMichigan Department of Natural Resources; cTexas Parks and Wildlife Department; dMissouri Department of Conservation, 5. Arkansas Game and Fish Commission CONTACT Kaitlyn M. Wagner miedkait@rams.colostate.edu
ABSTRACT
Background/Introduction: Chronic wasting disease (CWD) is an invariably fatal prion disease affecting captive and free-ranging cervids, including white-tailed deer, mule deer, moose, elk, and reindeer. Since the initial description of the disease in the 1960’s, CWD has spread to 23 states, 3 Canadian Provinces, South Korea, Norway and, most recently, Finland. While some outbreaks of CWD were caused by transport of infected animals from endemic regions, the origin of CWD in other epizootics is unclear and has not been characterized. Previous studies have shown that there are two distinct strains of CWD. However, the continuous spread and the unclear origin of several outbreaks warrant continued surveillance and further characterization of strain diversity.
Materials and Methods: To address these knowledge gaps, we used biochemical tests to assess strain differences between CWD outbreaks in Michigan, Texas, Missouri, and Colorado, USA. Brain or lymph node samples were homogenized and digested in 50 µg/mL proteinase K (PK). These samples were then run on a Western blot to assess glycoform ratio and electrophoretic mobility. Texas samples were digested in 100 µg/mL PK. To assess conformational stability, brain or lymph node homogenates were incubated in increasing concentrations of guanidine hydrochloride from 0 M to 4 M in 0.5 M increments. Samples were then precipitated in methanol overnight, washed and PK digested in 50 µg/mL PK before slot blotting.
Results: Our results have found significant differences in glycoform ratio between CWD from Michigan and Colorado, but no differences were observed in conformational stability assays. Interestingly, when testing our CWD isolates from Texas to analyse electrophoretic mobility and glycoform ratio, we found that these samples did not exhibit the characteristic band shift when treated with PK, but PK resistant material remained. Additionally, results from our conformational stability assay demonstrate a unique profile of these Texas isolates. Testing of samples from Missouri is currently underway.
Conclusions: Thus far, our data indicate that there are strain differences between CWD circulating in Michigan and CWD in Colorado and provide important insight into CWD strain differences between two non-contiguous outbreaks. We have also identified a unique strain of CWD in Texas with biochemical strain properties not seen in any of our other CWD isolates. These results highlight the importance of continued surveillance to better understand this devastating disease. These results have important implications for CWD emergence, evolution and our understanding of prion strain heterogeneity on the landscape.
www.tandfonline.com/doi/full/10.1080/19336896.2019.1615197
Breeding CWD from Cervid?
''However, to date, there are no reports of polymorphic cervid PrP alleles providing absolute resistance to CWD. Studies on polymorphisms have focused on those found in CWD-endemic areas, with the hope that understanding the role of an animal's genetics in CWD can help to predict, contain, or prevent transmission of CWD.''
pubmed.ncbi.nlm.nih.gov/33668798/
The presence of aa96S has been associated with slowed disease progression, longer life span among captive deer,Citation26,27 and does not appear to affect the rate at which prions are shed from infected individuals.Citation38 Additionally, CWD infected mule deer have been found to excrete pathogenic prions while asymptomatic.Citation39 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.
www.tandfonline.com/doi/full/10.1080/19336896.2015.1115179
***> at present, no PrPC allele conferring absolute resistance in cervids has been identified.
J Gen Virol. 2017 Nov; 98(11): 2882–2892.
Published online 2017 Oct 23. doi: 10.1099/jgv.0.000952
Estimating chronic wasting disease susceptibility in cervids using real-time quaking-induced conversion
Chronic wasting disease (CWD) resistance in cervids is often characterized as decreased prevalence and/or protracted disease progression in individuals with specific alleles; at present, no PrPC allele conferring absolute resistance in cervids has been identified.
www.ncbi.nlm.nih.gov/pmc/articles/PMC5845664/pdf/jgv-98-2882.pdf
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
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
web.archive.org/web/20161024005615/http://prion2016.org/dl/newsletter_03.pdf
chronic-wasting-disease.blogspot.com/2017/04/
''There are no known familial or genetic TSEs of animals, although polymorphisms in the PRNP gene of some species (sheep for example) may influence the length of the incubation period and occurrence of disease.''
c) The commonest form of CJD occurs as a sporadic disease, the cause of which is unknown, although genetic factors (particularly the codon 129 polymorphism in the prion protein gene (PRNP)) influence disease susceptibility. The familial forms of human TSEs (see Box 1) appear to have a solely genetic origin and are closely associated with mutations or insertions in the PRNP gene. Most, but not all, of the familial forms of human TSEs have been transmitted experimentally to animals. There are no known familial or genetic TSEs of animals, although polymorphisms in the PRNP gene of some species (sheep for example) may influence the length of the incubation period and occurrence of disease.
assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/209755/Part_1_-_Introduction.pdf
Examining PRNP gene frequencies and ‘resistance’ to chronic wasting disease
ACTIVE
By National Wildlife Health Center July 12, 2023
Overview Science
Multiple studies have demonstrated that various alleles of the cervid prion protein (PRNP) gene affect chronic wasting disease (CWD) progression.
Why this matters: Specific genetic differences in the cervid prion protein gene have been linked to disease ‘resistance’ and there is some evidence that gene frequencies in wild populations with high CWD prevalence are shifting towards these ‘resistant’ genotypes. It has been argued that this shift may eventually control CWD in the wild. A thorough examination of published science, however, suggests the situation may be more complex.
White-tailed deer in snow with forest in background and dried grass in foreground.
In white-tailed deer (Odocoileus virginianus), a putative ‘resistance’ allele encodes serine at amino acid 96 (96S) of the prion protein instead of the more common glycine (96G). Similarly, in mule deer (O. hemionus), a putative ‘resistance’ allele encodes phenylalanine at amino acid 225 (225F) instead of serine (225S). CWD has been found at lower abundance in heterozygous white-tailed deer with the 96S allele (96GS) and heterozygous mule deer with the 225F allele (225SF); CWD in homozygous 96S or 225F deer is rare (Johnson et al. 2006, Jewell et al. 2005). In experimental challenge studies all deer with 96S or 225F alleles (heterozygous or homozygous) contract CWD (Johnson et al. 2011, Wolfe et al. 2014, Plummer et al. 2017), but the presence of 96S or 225F, respectively, extends the incubation period. Although a prolonged incubation period may allow additional time for CWD+ deer to reproduce, it also increases opportunities for disease transmission and may allow disease prevalence to rise to a new equilibrium within endemic regions.
To increase our understanding of the potential impacts of disease-modifying alleles on CWD, the USGS National Wildlife Health Center and the Wisconsin Department of Natural Resources are examining PRNP gene frequencies in white-tailed deer to assess whether the relative abundance of Wisconsin deer expressing 96S has changed since the beginning of the epizootic. However, even if populations are shifting to higher frequencies of 96S or 225F, the resulting CWD epizootic trajectory may not be improved. Genetic resistance that can prevent infection by specific strains of pathogens must be distinguished from resistance that can prevent infection by all strains of that pathogen. In the context of CWD, the disease-modifying properties of 96S or 225F must be evaluated within a broader paradigm not only of the strains of CWD in circulation today, but also those that could arise in the future. For example, white-tailed deer with histidine at PRNP allele 95 give rise to a new emergent strain of CWD (termed H95+) when they are infected with the “wild-type” strain of CWD currently spreading in white-tailed deer. This H95+ CWD strain is likely to have very high attack rates in 96S deer (Duque Velasquez et al. 2015, Duque Velasquez et al. 2020). Similarly, serial passage of CWD in 225F mule-deer could stabilize a new strain adapted to 225F mule deer. Emergent strains of CWD prions may also have expanded host ranges and enhanced zoonotic potential (Herbst et al. 2017).
If the putative ‘resistance’ to CWD can be demonstrated, it should likely be considered temporary. As was observed with COVID-19, the evolutionary pattern of host resistance followed by pathogen adaptation is typical for infectious diseases and there are no known reasons to except CWD from this paradigm. The only known genetic modification that can induce general resistance to all prion strains are mutations that ablate expression of the mammalian prion protein. The resistance of cervids or other mammals to prion disease is a continuum of vulnerability that reflects both the host’s prion protein sequence and the specific prion strain that it is exposed to.
www.usgs.gov/centers/nwhc/science/examining-prnp-gene-frequencies-and-resistance-chronic-wasting-disease
“If slower disease progression results in longer-lived, infected deer with longer periods of infectiousness, resistance may lead to increased disease transmission rates, higher prion concentrations in the environment, and increased prevalence, as has been observed in some captive deer herds (Miller et al., 2006; Keane et al., 2008a).”
Genetic susceptibility to chronic wasting disease in free-ranging white-tailed deer: Complement component C1q and Prnp polymorphisms
Julie A. Blanchong a, *, Dennis M. Heisey b , Kim T. Scribner c , Scot V. Libants d , Chad Johnson e , Judd M. Aiken e , Julia A. Langenberg f , Michael D. Samuel g
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Identifying the genetic basis for heterogeneity in disease susceptibility or progression can improve our understanding of individual variation in disease susceptibility in both free-ranging and captive populations. What this individual variation in disease susceptibility means for the trajectory of disease in a population, however, is not straightforward. For example, the greater, but not complete, resistance to CWD in deer with at least one Serine (S) at amino acid 96 of the Prnp gene appears to be associated with slower progression of disease (e.g., Johnson et al., 2006; Keane et al., 2008a). If slower disease progression results in longer-lived, infected deer with longer periods of infectiousness, resistance may lead to increased disease transmission rates, higher prion concentrations in the environment, and increased prevalence, as has been observed in some captive deer herds (Miller et al., 2006; Keane et al., 2008a). Alternatively, if the slower progression of disease in resistant deer is not associated with longer periods of infectiousness, but might instead indicate a higher dose of PrPCWD is required for infection, transmission rates in the population could decline especially if, as in Wisconsin, deer suffer high rates of mortality from other sources (e.g., hunting). Clearly, determining the relationship between genetic susceptibility to infection, dose requirements, disease progression, and the period of PrPCWD infectiousness are key components for understanding the consequences of CWD to free-ranging populations.
pubmed.ncbi.nlm.nih.gov/19723593/#:~:text=After%20controlling%20for%20Prnp%2C%20we,strongly%20associated%20with%20CWD%20susceptibility.
web.archive.org/web/20121114223603/http://forest.wisc.edu/files/pdfs/samuel/2009%20blanchong%20et%20al%20genetic%20susceptibility%20chronic%20wasting.pdf
The presence of aa96S has been associated with slowed disease progression, longer life span among captive deer,Citation26,27 and does not appear to affect the rate at which prions are shed from infected individuals.Citation38 Additionally, CWD infected mule deer have been found to excrete pathogenic prions while asymptomatic.Citation39 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.Citation40 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).Citation26,30
www.tandfonline.com/doi/full/10.1080/19336896.2015.1115179
www.ncbi.nlm.nih.gov/pmc/articles/PMC4964855/pdf/kprn-09-06-1115179.pdf
Published: 07 October 2021
Review on PRNP genetics and susceptibility to chronic wasting disease of Cervidae
To date, chronic wasting disease (CWD) is the most infectious form of prion disease affecting several captive, free ranging and wild cervid species. Responsible for marked population declines in North America, its geographical spread is now becoming a major concern in Europe. Polymorphisms in the prion protein gene (PRNP) are an important factor influencing the susceptibility to prions and their rate of propagation. All reported cervid PRNP genotypes are affected by CWD. However, in each species, some polymorphisms are associated with lower attack rates and slower progression of the disease. This has potential consequences in terms of genetic selection, CWD diffusion and strain evolution. CWD also presents a zoonotic risk due to prions capacity to cross species barriers. This review summarizes our current understanding of CWD control, focusing on PRNP genetic, strain diversity and capacity to infect other animal species, including humans.
snip...
However, the characterization of the infecting strain(s) in these natural conditions was not always assessed. This information is necessary for identifying spill over hosts and estimating the zoonotic potential [53]. Such breeding selection might also contribute to the emergence of new CWD strains [98].
snip...
CWD positive animals with extended time before they succumb to disease likely represent a source of chronic prion shedding within populations and may contribute to environmental contamination.
veterinaryresearch.biomedcentral.com/articles/10.1186/s13567-021-00993-z
GENETICALLY MODIFIED DEER WON’T STOP CWD. HERE ARE 7 REASONS WHY
May 21, 2024 By: NDA Staff
deerassociation.com/genetically-modified-deer-wont-stop-cwd-here-are-7-reasons-why/
MEANWHILE, BACK AT THE RANCH$$$
Chronic Wasting Disease CWD TSE PRION DISEASE ENVIRONMENTAL FACTORS
CWD TSE ENVIRONMENTAL FACTORS
CWD TSE PRION CERVID ENVIRONMENTAL RISK FACTORS 2023
For what it's worth, Back around 2000, 2001, or so, I was corresponding with officials abroad during the bse inquiry, passing info back and forth on CJD and Nutritional Supplements and BSE here in the USA, and some officials from here inside USDA aphis FSIS et al, in fact helped me get into the USA 50 state emergency BSE conference call way back. That one was a doozy. But I always remember what “deep throat” as i called them, I never knew who they were, but I never forgot what i was told decades ago, amongst them was ;
Some unofficial information from a source on the inside looking out -
Confidential!!!!
As early as 1992-3 there had been long studies conducted on small pastures containing scrapie infected sheep at the sheep research station associated with the Neuropathogenesis Unit in Edinburgh, Scotland. Whether these are documented...I don't know. But personal recounts both heard and recorded in a daily journal indicate that leaving the pastures free and replacing the topsoil completely at least 2 feet of thickness each year for SEVEN years....and then when very clean (proven scrapie free) sheep were placed on these small pastures.... the new sheep also broke out with scrapie and passed it to offspring. I am not sure that TSE contaminated ground could ever be free of the agent!! A very frightening revelation!!!
---end personal email---end...tss
So, this is what we leave our children and grandchildren?..
"Additionally, we have determined that prion seeding activity is retained for at least fifteen years at a contaminated site following attempted remediation."
Detection of prions in soils contaminated by multiple routes
Stuart Siegfried Lichtenberg1,2 , Heather Inzalaco3 , Sam Thomas4 , Dan Storm5 , Dan Walsh6
1Department of Veterinary and Biomedical Sciences, University of Minnesota, St. Paul, Minnesota, U.S.A.
2Minnesota Center for Prion Research and Outreach, University of Minnesota, St. Paul, Minnesota, U.S.A.
3 Wisconsin Cooperative Wildlife Research Unit, Department of Forest and Wildlife Ecology, University of Wisconsin-Madison, Madison, Wisconsin, U.S.A
4Department of Soil Science, University of Wisconsin-Madison, Madison, Wisconsin, U.S.A.
5Wisconsin Department of Natural Resources, Eau Claire, Wisconsin, U.S.A.
6U.S. Geological Survey, Montana Cooperative Wildlife Research Unit, University of Montana, Missoula, Montana, U.S.A.
Aims: Free-ranging animals afflicted with transmissible spongiform encephalopathies frequently shed infectious prions into the broader environment. The quintessential example is chronic wasting disease, the TSE of cervids. Over the course of the disease, an infected animal will shed infectious prions in blood, urine, saliva, and feces. Upon death, the total prion load interred in the animal’s tissues will be deposited wherever the animal falls. This contamination creates substantial risk to naïve animals, and likely contributes to disease spread. Identification and quantification of prions at contamination hotspots is essential for any attempt at mitigation of environmental transmission.
Materials and Methods: Surfactant extraction of soils followed by precipitation yields a sample that is amenable to analysis by real-time quaking induced conversion. However, differences in extraction yield are apparent depending on the properties of the matrix from which the prions are being extracted, principally soil clay content.
Results: We are able to detect prion seeding activity at multiple types of environmental hotspots, including carcass sites, contaminated captive facilities, and scrapes (i.e. urine and saliva). Differences in relative prion concentration vary depending on the nature and source of the contamination. Additionally, we have determined that prion seeding activity is retained for at least fifteen years at a contaminated site following attempted remediation.
Conclusions: Detection of prions in the environment is of the utmost importance for controlling chronic wasting disease spread. Here, we have demonstrated a viable method for detection of prions in complex environmental matrices. However, it is quite likely that this method underestimates the total infectious prion load in a contaminated sample, due to incomplete recovery of infectious prions. Further refinements are necessary for accurate quantification of prions in such samples, and to account for the intrinsic heterogeneities found in the broader environment.
Funded by: Wisconsin Department of Natural Resources
=====end
Prion 2023 Abstracts
prion2023.org/wp-content/uploads/2023/10/Meeting-book-final-version2.pdf
Artificial mineral sites that pre-date endemic chronic wasting disease become prion hotspots
Heather N'te Inzalaco1,1, Marie L. Gilbertson1, Stephanie J. Katircioglu1, Kenny Lepard2, Jordan McEarl2, Austin Bibb2, Jeremy Dennison2, Dan Grove3, Allen Houston4, Dan J. Storm5, Dan P. Walsh6, Wendy C. Turner7, Stuart S. Lichtenberg8 1Wisconsin Cooperative Wildlife Research Unit, Department of Forest and Wildlife Ecology, University of Wisconsin, Madison, Madison, USA. 2Tennessee Wildlife Resources Agency, Jackson, USA. 3University of Tennessee Extension, Nashville, USA. 4University of Tennessee -Knoxville, School of Forest, Wildlife, and Fisheries, Ames Research and Education Center, Grand Junction, USA. 5Wisconsin Department of Natural Resources, Eau Claire, USA. 6U.S. Geological Survey, Montana Cooperative Wildlife Research Unit, Department of Ecosystem and Conservation Sciences, University of Montana, Missoula, USA. 7U.S. Geological Survey, Wisconsin Cooperative Wildlife Research Unit, Department of Forest and Wildlife Ecology, University of Wisconsin – Madison, Madison, USA. 8Department of Veterinary and Biomedical Sciences, University of Minnesota, Minnesota, USA
Abstract
Chronic wasting disease (CWD) is a highly contagious, fatal neurodegenerative disease caused by infectious prions (PrPCWD) affecting wild and captive cervids. As CWD continues to spread broadly over North America, factors influencing geographic expansion remain poorly understood. CWD-infected cervids shed infectious prions in urine, feces, and saliva. Activities that result in cervids aggregating and shedding PrPCWD may result in ‘hot spots’ of environmental PrPCWD deposition, however empirical data regarding the impact of deer attractants on environmental PrPCWD deposition is lacking. Filling this knowledge gap could inform deer and disease management. In 2018, the southwest region of Tennessee, U.S.A. experienced a CWD outbreak. The Ames Research and Educational Center property, centrally located within the CWD zone of southwest Tennessee, contains 49 historical mineral supplementation sites that were decommissioned in 2012. Here, we demonstrate that 32 of the 49 (65%) mineral sites within Ames established prior to the regional CWD outbreak, serve as foci of environmental PrPCWD contamination. Detection of PrPCWD in soils from these artificial mineral sites was dependent on site-specific management efforts. Soil physical properties were very similar across sites and no correlation between PrPCWD detection and soil physical properties was found. The detection of PrPCWD in soils at attractant sites within an endemic CWD zone significantly advances our understanding of environmental PrPCWD accumulation dynamics, providing valuable information for advancing adaptive CWD management approaches.
int-cwd-sympo.org/wp-content/uploads/2023/06/final-agenda-with-abstracts.pdf
9 Carrot plants as potential vectors for CWD transmission.
Paulina Soto1,2, Francisca Bravo-Risi1,2, Claudio Soto1, Rodrigo Morales1,2
1Department of Neurology, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, USA. 2Universidad Bernardo O’Higgins, Santiago, Chile
***> We show that edible plant components can absorb prions from CWD-contaminated soils and transport them to their aerial parts.
***> Our results indicate that edible plants could participate as vectors of CWD transmission
=====
intcwdsympo.files.wordpress.com/2023/06/final-agenda-with-abstracts.pdf?force_download=true
***> Infectious agent of sheep scrapie may persist in the environment for at least 16 years
***> Nine of these recurrences occurred 14–21 years after culling, apparently as the result of environmental contamination, but outside entry could not always be absolutely excluded.
JOURNAL OF GENERAL VIROLOGY Volume 87, Issue 12
Infectious agent of sheep scrapie may persist in the environment for at least 16 years Free
www.microbiologyresearch.org/content/journal/jgv/10.1099/vir.0.82011-0
Rapid recontamination of a farm building occurs after attempted prion removal
First published: 19 January 2019 doi.org/10.1136/vr.105054
The data illustrates the difficulty in decontaminating farm buildings from scrapie, and demonstrates the likely contribution of farm dust to the recontamination of these environments to levels that are capable of causing disease. snip...
This study clearly demonstrates the difficulty in removing scrapie infectivity from the farm environment. Practical and effective prion decontamination methods are still urgently required for decontamination of scrapie infectivity from farms that have had cases of scrapie and this is particularly relevant for scrapie positive goatherds, which currently have limited genetic resistance to scrapie within commercial breeds.24 This is very likely to have parallels with control efforts for CWD in cervids.
bvajournals.onlinelibrary.wiley.com/doi/abs/10.1136/vr.105054
***>This is very likely to have parallels with control efforts for CWD in cervids.
pubmed.ncbi.nlm.nih.gov/30602491/
Front. Vet. Sci., 14 September 2015 | doi.org/10.3389/fvets.2015.00032
Objects in contact with classical scrapie sheep act as a reservoir for scrapie transmission
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.
journal.frontiersin.org/article/10.3389/fvets.2015.00032/full
172. Establishment of PrPCWD extraction and detection methods in the farm soil
Conclusions: Our studies showed that PrPCWD persist in 0.001% CWD contaminated soil for at least 4 year and natural CWD-affected farm soil. When cervid reintroduced into CWD outbreak farm, the strict decontamination procedures of the infectious agent should be performed in the environment of CWD-affected cervid habitat.
www.tandfonline.com/doi/full/10.1080/19336896.2019.1615197
Plants as vectors for environmental prion transmission
Published: November 09, 2023DOI: doi.org/10.1016/j.isci.2023.108428
Advertisement Highlights
• Abnormal prion protein can enter the roots of plants
• Plants can translocate detectable levels of prions to aerial tissues
•Animals exposed to prion-contaminated plant tissues can acquire disease
•Contaminated plants may represent a route of prion exposure
Snip…
Nonetheless, our finding of accumulation of two prion strains by a variety of plants grown hydroponically, in agar, or on soil supports the potential for plants to acquire CWD, scrapie, or other prions from the environment and transmit prion disease to susceptible hosts, making plants a plausible vector for prion diseases in wildlife, livestock, and humans. The potential for plants to serve as vectors for prion disease has implications for the disposal of infected carcasses, grazing practices, and the use and transport of potentially contaminated crop materials.
www.cell.com/iscience/pdf/S2589-0042(23)02505-1.pdf
www.cell.com/iscience/fulltext/S2589-0042(23)02505-1?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS2589004223025051%3Fshowall%3Dtrue
Carrot plants as potential vectors for CWD transmission.
The PMCA analysis demonstrated CWD seeding activity in soils contaminated with CWD prions and in carrot plants (leaves and roots) grown on them. Bioassays showed that both plants and roots contained CWD prions sufficiently to induce disease. As expected, animals treated with prion-infected soils developed prion disease at shorter incubation periods (and complete attack rates) compared to plant components. We show that edible plant components can absorb prions from CWD-contaminated soils and transport them to their aerial parts. Our results indicate that edible plants could participate as vectors of CWD transmission.
intcwdsympo.files.wordpress.com/2023/06/final-agenda-with-abstracts.pdf?force_download=true
“In addition, hay and straw from the United States and Canada must be accompanied by a certificate from a public veterinarian that the product has been harvested in states or provinces where Chronic Wasting Disease has not been detected on deer.”
Regulation No. 1599 of 2018 on additional requirements for the import of hay and straw for used for animal feed.
Country Norway
Type of law Regulation
Source
FAO , FAOLEX
In addition, hay and straw from the United States and Canada must be accompanied by a certificate from a public veterinarian that the product has been harvested in states or provinces where Chronic Wasting Disease has not been detected on deer.
faolex.fao.org/docs/pdf/nor189761.pdf
Chronic wasting disease detection in environmental and biological samples from a taxidermy site
Paulina Sotoa,b, J. Hunter Reedc, Mitch Lockwoodc, and Rodrigo Moralesa,b
aDepartment of Neurology, McGovern Medical School, University of Texas Health Science Center at Houston, Texas, USA; bUniversidad Bernardo O’Higgins, Santiago, Chile; cTexas Parks and Wildlife Department, Texas, USA
Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy affecting captive and free-ranging cervids (e.g., mule deer, white-tailed deer, elk, reindeer, and moose). Nowadays, CWD is widely distributed in North America. It is suggested that CWD spreads due to direct animal contact or through exposure to contaminated environments previously inhabited by infected animals. CWD may also be spread through the movement of infected animals and carcasses. Taxidermy practices involve processing deer tissues (or whole animal carcasses). In many cases, the CWD status of processed animals is unknown. This can generate risks of disease spread and transmission. Taxidermy practices include different steps involving physical, chemical, and biological procedures. Without proper tissue handling or disposal practices, taxidermist facilities may become a focus of prion infectivity.
Aims: In this study, we evaluated the presence of infectious prions in a taxidermy facility believed to be exposed to CWD. Detection was performed using the Protein Misfolding Cyclic Amplification (PMCA) technique in biological and inert environmental samples.
Methods: We collected biological and environmental samples (plants, soils, insects, excreta, and others) from a taxidermy facility, and we tested these samples using the PMCA technique. In addition, we swabbed different surfaces possibly exposed to CWD-infected animals. For the PMCA reaction, we directly used a swab piece or 10 µL of 20% w/v homogenized samples.
Results: The PMCA analysis demonstrated CWD seeding activity in some of the components of this facility, including insects involved in head processing, soils, and a trash dumpster.
Conclusions: Different areas of this property were used for various taxidermy procedures. We were able to detect the presence of prions in i) soils that were in contact with the heads of dead animals, ii) insects involved in the cleaning of skulls, and iii) an empty dumpster where animal carcasses were previously placed. This is the first report demonstrating that swabbing is a helpful method to screen for prion infectivity on surfaces potentially contaminated with CWD. These findings are relevant as this swabbing and amplification strategy may be used to evaluate the disease status of other free-ranging and captive settings where there is a concern for CWD transmissions, such as at feeders and water troughs with CWD-exposed properties. This approach could have substantial implications for free-ranging cervid surveillance as well as in epidemiological investigations of CWD.
Funded by: USDA
Grant number: AP20VSSPRS00C143
PRION 2022 ABSTRACTS, AND A BIG THANK YOU TO On behalf of the Prion2020/2022 Congress Organizing Committee and the NeuroPrion Association, we heartily invite you to join us for the International Conference Prion2020/2022 from 13.-16. September 2022 in Göttingen.
Prion 2022 Conference abstracts: pushing the boundaries
www.tandfonline.com/doi/full/10.1080/19336896.2022.2091286
Large-scale PMCA screening of retropharyngeal lymph nodes and in white-tailed deer and comparisons with ELISA and IHC: the Texas CWD study
Rebeca Benaventea, Paulina Sotoa, Mitch Lockwoodb, and Rodrigo Moralesa aDepartment of Neurology, McGovern Medical School, University of Texas Health Science Center at Houston, Texas, USA; bTexas Park and Wildlife Department, Texas, USA
Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy that affects various species of cervids, and both free-ranging and captive animals. Until now, CWD has been detected in 3 continents: North America, Europe, and Asia. CWD prevalence in some states may reach 30% of total animals. In Texas, the first case of CWD was reported in a free-range mule deer in Hudspeth and now it has been detected in additional 14 counties. Currently, the gold standard techniques used for CWD screening and detection are ELISA and immunohistochemistry (IHC) of obex and retropharyngeal lymph nodes (RPLN). Unfortunately, these methods are known for having a low diagnostic sensitivity. Hence, many CWD-infected animals at pre-symptomatic stages may be misdiagnosed. Two promising in vitro prion amplification techniques, including the real-time quaking-induced conversion (RT-QuIC) and the protein misfolding cyclic amplification (PMCA) have been used to diagnose CWD and other prion diseases in several tissues and bodily fluids. Considering the low cost and speed of RT-QuIC, two recent studies have communicated the potential of this technique to diagnose CWD prions in RPLN samples. Unfortunately, the data presented in these articles suggest that identification of CWD positive samples is comparable to the currently used ELISA and IHC protocols. Similar studies using the PMCA technique have not been reported.
Aims: Compare the CWD diagnostic potential of PMCA with ELISA and IHC in RPLN samples from captive and free-range white-tailed deer. Material and Methods: In this study we analyzed 1,003 RPLN from both free-ranging and captive white-tailed deer collected in Texas. Samples were interrogated with the PMCA technique for their content of CWD prions. PMCA data was compared with the results obtained through currently approved techniques.
Results: Our results show a 15-fold increase in CWD detection in free-range deer compared with ELISA. Our results unveil the presence of prion infected animals in Texas counties with no previous history of CWD. In the case of captive deer, we detected a 16% more CWD positive animals when compared with IHC. Interestingly, some of these positive samples displayed differences in their electroforetic mobilities, suggesting the presence of different prion strains within the State of Texas.
Conclusions: PMCA sensitivity is significantly higher than the current gold standards techniques IHC and ELISA and would be a good tool for rapid CWD screening.
Funded by: USDA
Grant number: AP20VSSPRS00C143
PRION 2022 ABSTRACTS, AND A BIG THANK YOU TO On behalf of the Prion2020/2022 Congress Organizing Committee and the NeuroPrion Association, we heartily invite you to join us for the International Conference Prion2020/2022 from 13.-16. September 2022 in Göttingen.
Prion 2022 Conference abstracts: pushing the boundaries
www.tandfonline.com/doi/full/10.1080/19336896.2022.2091286
Shedding of Chronic Wasting Disease Prions in Multiple Excreta Throughout Disease Course in White-tailed Deer
Nathaniel D. Denkersa, Erin E. McNultya, Caitlyn N. Krafta, Amy V. Nallsa, Joseph A. Westricha, Wilfred Goldmannb, Candace K. Mathiasona, and Edward A. Hoovera
aPrion Research Center, College of Veterinary Medicine and Biological Sciences, Department of Microbiology, Immunology, and Pathology; Colorado State University, Fort Collins, CO, USA; bDivision of Infection and Immunity, The Roslin Institute and the Royal Dick School of Veterinary Studies, University of Edinburgh, Midlothian, UK
Aims: Chronic wasting disease (CWD) now infects cervids in South Korea, North America, and Scandinavia. CWD is unique in its efficient transmission and shedding of prions in body fluids throughout long course infections. Questions remain as to the magnitude of shedding and the route of prion acquisition. As CWD continues to expand, the need to better understand these facets of disease becomes more pertinent. The purpose of the studies described was to define the longitudinal shedding profile of CWD prions in urine, saliva, and feces throughout the course of infection in white-tailed deer.
Material and Methods: Twelve (12) white-tailed deer were inoculated with either 1 mg or 300ng of CWD. Urine, saliva, and feces were collected every 3-month post-inoculation (MPI) throughout the study duration. Cohorts were established based on PNRP genotype: codon 96 GG (n = 6) and alternate codons 96 GS (n = 5) & 103NT (n = 1). Urine and saliva were analyzed using iron-oxide magnetic extraction (IOME) and real-time quaking induced conversion (RT-QuIC)(IQ). Feces were subjected to IOME, followed by 4 rounds protein misfolding cyclic amplification (PMCA) with products analyzed by RT-QuIC (IPQ). To determine whether IPQ may be superior to IQ, a subset of urine and saliva were also tested by IPQ. Results were compared with clinical disease status.
Results: Within the 96 GG cohort, positive seeding activity was detected in feces from all deer (100%), in saliva from 5 of 6 (83%), and in urine from 4 of 6 (66%). Shedding in all excreta occurred at, or just after, the first positive tonsil biopsy result. In the 96 GS/103NT cohort, positive seeding activity could be detected in feces from 3 of 6 (50%) deer, saliva in 2 of 6 (33%), and urine in 1 of 6 (16%). Shedding in excreta was detected >5 months after the first tonsil positive result. Four of six 96 GG deer developed clinical signs of CWD, whereas only 2 of the 96 GS/103NT did. Shedding was more frequently detected in deer with clinical disease. The IPQ protocol did not significantly improve detection in saliva or urine samples, however, it significantly augmented detection in feces by eliminating non-specific background commonly experienced with IQ. Negative control samples remained negative in samples tested.
Conclusions: These studies demonstrate: (a) CWD prion excretion occurs throughout infection; (2) PRNP genotype (GG≫GS/NT) influences the excreta shedding; and (3) detection sensitivity in excreta can vary with different RT-QuIC protocols. These results provide a more complete perspective of prion shedding in deer during the course of CWD infection.
Funded by: National Institutes of Health (NIH)
Grant number: RO1-NS061902-09 R to EAH, PO1-AI077774 to EAH, and R01-AI112956-06 to CKM
Acknowledgement: We abundantly thank Sallie Dahmes at WASCO and David Osborn and Gino D’Angelo at the University of Georgia Warnell School of Forestry and Natural Resources for their long-standing support of this work through provision of the hand-raised, CWD-free, white-tailed deer used in these studies
Carrot plants as potential vectors for CWD transmission
Paulina Sotoa,b, Francisca Bravo-Risia,b, Claudio Sotoa, and Rodrigo Moralesa,b
aDepartment of Neurology, McGovern Medical School, University of Texas Health Science Center at Houston, Texas, USA; bUniversidad Bernardo O’Higgins, Santiago, Chile
Prion diseases are infectious neurodegenerative disorders afflicting humans and other mammals. These diseases are generated by the misfolding of the cellular prion protein into a disease-causing isoform. Chronic wasting disease (CWD) is a prevalent prion disease affecting cervids (captive and free-range). CWD is thought to be transmitted through direct animal contact or by indirect exposure to contaminated environments. Many studies have shown that infectious prions can enter the environment through saliva, feces, or urine from infected animals and decaying carcasses. However, we do not fully understand the specific contribution of each component to disease transmission events. Plants are logical environmental components to be evaluated since they grow in environments contaminated with CWD prions and are relevant for animal and human nutrition.
Aims: The main objective of this study is to study whether prions are transported to the roots and leaves of carrots, an edible plant commonly used in the human diet and as deer bait.
Methods: We have grown carrot plants in CWD-infected soils. After 90 days, we harvested the carrots and separated them from the leaves. The experiment was controlled by growing plants in soil samples treated with brain extracts from healthy animals. These materials were interrogated for their prion seeding activity using the Protein Misfolding Cyclic Amplification (PMCA) technique. Infectivity was evaluated in mouse bioassays (intracerebral injections in Tg1536 mice). The animals were sacrificed when they showed established signs of prion disease. Animals not displaying clinical signs were sacrificed at 600 days post-inoculation.
Results: The PMCA analysis demonstrated CWD seeding activity in soils contaminated with CWD prions, as well as in carrot plants (leaves and roots) grown on them. Bioassays demonstrated that both leaves and roots contained CWD prions in sufficient quantities to induce disease (92% attack rate). As expected, animals treated with prion-infected soils developed prion disease at shorter incubation periods (and complete attack rates) compared to plant components. Animals treated with soil and plant components exposed with CWD-free brain extracts did not display prion-associated clinical signs or evidence of sub-clinical prion infection.
Conclusions: We show that edible plant components can absorb prions from CWD contaminated soils and transport them to their aerial parts. Our results indicate that plants could participate as vectors of CWD transmission. Importantly, plants designated for human consumption represent a risk of introducing CWD prions into the human food chain.
Funded by: NIH
Grant number: R01AI132695
www.tandfonline.com/doi/full/10.1080/19336896.2022.2091286
October 6th-12th, 126th Meeting 2022 Resolutions
RESOLUTION NUMBER: 30 Approved
SOURCE: COMMITTEE ON WILDLIFE
SUBJECT MATTER: Chronic Wasting Disease Carcass Disposal Dumpster Management and Biosecurity
BACKGROUND INFORMATION:
State and tribal wildlife agencies may identify collection points (dumpsters) within an identified chronic wasting disease (CWD) management zone for the disposal of hunter-harvested cervid carcasses to remove potentially infected carcasses off the landscape for disposal by an approved method (Gillin & Mawdsley, 2018, chap.14). However, depending on their placement and maintenance these dumpsters could potentially increase the risk of CWD transmission.
In several different states, photographic evidence has shown dumpsters in state identified CWD management zones overflowing with deer carcasses and limbs scattered on the land nearby. This could provide an opportunity for scavengers to potentially move infected carcass material to non-infected zones or increase contamination of the ground material around the dumpster’s location.
Federal guidance does not explicitly address uniform standards for collection locations for carcasses of free-ranging cervids; however, the United States Department of Agriculture, Animal and Plant Health Inspection Service, Veterinary Services Program Standards on CWD outlines procedures for carcass disposal, equipment sanitation, and decontamination of premises for captive cervid facilities.
RESOLUTION:
The United States Animal Health Association urges the Association of Fish and Wildlife Agencies (AFWA), Wildlife Health Committee to further refine the AFWA Technical Report on Best Management Practices for Prevention, Surveillance, and Management of Chronic Wasting Disease; Chapter 14, Carcass Disposal to address the placement and management of chronic wasting disease carcass disposal dumpsters or other carcass collection containers.
Reference:
1. Gillin, Colin M., and Mawdsley, Jonathan R. (eds.). 2018. AFWA Technical Report on Best Management Practices for Surveillance, Management and Control of Chronic Wasting Disease. Association of Fish and Wildlife Agencies, Washington, D. C. 111 pp.
www.usaha.org/upload/Resolution/2022/2022_Resolution_30_CWD_Dumpste.pdf
Trucking CWD TSE PrP
Friday, December 14, 2012
DEFRA U.K. What is the risk of Chronic Wasting Disease CWD being introduced into Great Britain? A Qualitative Risk Assessment October 2012
snip...
The rate of transmission of CWD has been reported to be as high as 30% and can approach 100% among captive animals in endemic areas (Safar et al., 2008).
snip...
In summary, in endemic areas, there is a medium probability that the soil and surrounding environment is contaminated with CWD prions and in a bioavailable form. In rural areas where CWD has not been reported and deer are present, there is a greater than negligible risk the soil is contaminated with CWD prion.
snip...
In summary, given the volume of tourists, hunters and servicemen moving between GB and North America, the probability of at least one person travelling to/from a CWD affected area and, in doing so, contaminating their clothing, footwear and/or equipment prior to arriving in GB is greater than negligible. For deer hunters, specifically, the risk is likely to be greater given the increased contact with deer and their environment. However, there is significant uncertainty associated with these estimates.
snip...
Therefore, it is considered that farmed and park deer may have a higher probability of exposure to CWD transferred to the environment than wild deer given the restricted habitat range and higher frequency of contact with tourists and returning GB residents.
snip...
web.archive.org/web/20170404125557/http://webarchive.nationalarchives.gov.uk/20130822084033/http://www.defra.gov.uk/animal-diseases/files/qra_chronic-wasting-disease-121029.pdf
THE tse prion aka mad cow type disease is not your normal pathogen.
The TSE prion disease survives ashing to 600 degrees celsius, that’s around 1112 degrees farenheit.
you cannot cook the TSE prion disease out of meat.
you can take the ash and mix it with saline and inject that ash into a mouse, and the mouse will go down with TSE.
Prion Infected Meat-and-Bone Meal Is Still Infectious after Biodiesel Production as well.
the TSE prion agent also survives Simulated Wastewater Treatment Processes.
IN fact, you should also know that the TSE Prion agent will survive in the environment for years, if not decades.
you can bury it and it will not go away.
The TSE agent is capable of infected your water table i.e. Detection of protease-resistant cervid prion protein in water from a CWD-endemic area.
it’s not your ordinary pathogen you can just cook it out and be done
New studies on the heat resistance of hamster-adapted scrapie agent: Threshold survival after ashing at 600°C suggests an inorganic template of replication
www.pnas.org/content/97/7/3418.full
Prion Infected Meat-and-Bone Meal Is Still Infectious after Biodiesel Production
www.ncbi.nlm.nih.gov/pmc/articles/PMC2493038/
Detection of protease-resistant cervid prion protein in water from a CWD-endemic area
https://www.ncbi...nlm.nih.gov/pmc/articles/PMC2802782/pdf/prion0303_0171.pdf
Prions in Waterways
vimeo.com/898941380?fbclid=IwAR3Di7tLuU-iagCetdt4-CVPrOPQQrv037QS1Uxz0tX3z7BuvPeYlwIp7IY
A Quantitative Assessment of the Amount of Prion Diverted to Category 1 Materials and Wastewater During Processing
onlinelibrary.wiley.com/doi/10.1111/j.1539-6924.2012.01922.x/abstract
Rapid assessment of bovine spongiform encephalopathy prion inactivation by heat treatment in yellow grease produced in the industrial manufacturing process of meat and bone meals
bmcvetres.biomedcentral.com/track/pdf/10.1186/1746-6148-9-134.pdf
THURSDAY, FEBRUARY 28, 2019
BSE infectivity survives burial for five years with only limited spread
link.springer.com/content/pdf/10.1007%2Fs00705-019-04154-8.pdf
“Transmissible spongiform encephalopathy (TSE) agents have strain variations that influence disease phenotype and may affect the potential for interspecies transmission. Since deer and sheep may use the same grazing land, it is important to understand the potential transmission of TSEs between these species. The US scrapie isolate (No.13-7) had a 100% attack rate in white-tailed deer after oronasal challenge.”
www.ars.usda.gov/research/publications/publication/?seqNo115=405929
TUESDAY, JANUARY 16, 2024
CIDRAP launches international effort to prepare for possible chronic wasting disease spillover
Chronic Wasting Disease CWD TSE Prion Spillover to other Species, What If?
chronic-wasting-disease.blogspot.com/2024/01/cidrap-launches-international-effort-to.html
CWD, Plants, oh my…
www.cidrap.umn.edu/chronic-wasting-disease/plants-can-take-cwd-causing-prions-soil-lab-what-happens-if-they-are-eaten
THE following study is another band aid approach, to something that needed a tourniquet decades ago. instead of fixing the problem, let's cater to the industry some more...terry
Investigating potential inhibitory roles of organic copper and zinc in CWD prion protein misfolding and propagation
Joseph Hediger1, Peter Larsen2, Jason Bartz3, Randy DeYoung1, David Hewitt1, Mitch Lockwood4, Alynn Martin1, J. Hunter Reed4, Marc Schwabenlander2, Tiffany Wolf5, Michael Cherry1 1Caesar Kleberg Wildlife Research Institute, Kingsville, TX, USA. 2Minnesota Center for Prion Research and Outreach, St. Paul, MN, USA. 3Creighton University, Omaha, NE, USA. 4Texas Parks and Wildlife Department, Austin, TX, USA. 5University of Minnesota, St. Paul, MN, USA
Abstract
Positive cases of Chronic Wasting Disease (CWD) are spreading rapidly across the United States, Canada, and Europe. Although a treatment is currently unavailable for CWD, there is potential for molecules to bind to misfolded prions preventing or slowing subsequent protein misfolding. In a rodent model, orally administered copper inhibited the misfolding and propagation of infectious proteins. However, it is yet unknown how mineral status influences disease progression in cervids. We are working to determine if copper (Cu-AA) and zinc (Zn-AA) concentrations in target organs influence the propagation of misfolded CWD prions (PrPcwd). To do this we harvested 150 mature white-tailed deer (Odocoileus virginianus) spanning a gradient of Cu-AA and Zn-AA bioavailability in Texas, USA. Samples, including liver, brain, distal ilium, medial retropharyngeal lymph nodes, and tongue, were collected from 1) deer in South Texas with natural nutrition, 2) free-ranging deer with access to supplemental feed enhanced with Cu-AA and Zn-AA, and 3) captive deer fed exclusively feed with Cu-AA and Zn-AA supplementation. We will use prion misfolding cyclic amplification to evaluate the role of Cu-AA and Zn-AA concentrations in brain and lymphoid tissue in reducing PrPcwd, while accounting for CWD status and genetic susceptibility to CWD. This research has the potential to identify molecules that may serve as novel management options for CWD treatment and prevention.
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Genomic Predictions For Differential Susceptibility to Chronic Wasting Disease in Farmed U.S. White-tailed Deer
Christopher Seabury1, Tracy Nichols2
1Texas A&M University, College Station, USA. 2USDA APHIS Veterinary Services, Fort Collins, USA
Abstract
Despite advanced management practices, diagnostic surveillance, and depopulation of positive herds, the geographic expansion of chronic wasting disease (CWD) in U.S. white-tailed deer (Odocoileus virginianus; hereafter WTD) remains largely unabated. Therefore, a critical need exists to identify novel strategies that reduce the prevalence of CWD. Herein, we deploy a custom single nucleotide polymorphism (SNP) array to perform the largest genome-wide association study for CWD in farmed U.S. WTD to date; thereby confirming PRNP codon 96 as the largest-effect region of the WTD genome (P-value ≤ 5.99e-13; Proportion of Variance Explained ≥ 0.032). However, beyond PRNP, 25 significant SNPs (P-value ≤ 5e-05) also were detected, thereby implicating ≥ 25 unique positional candidate genes; many of which have been directly implicated in aspects Alzheimer’s, Parkinson’s, and various prion diseases. Our genome-wide association analyses unequivocally indicate that differential susceptibility to CWD and variation in natural disease progression have trait architectures comprised of very few moderate or large-effect genetic components, and many small-effect genetic components; which is consistent with most polygenic traits. Interestingly, genomic relationship matrix heritability estimates were high for both differential susceptibility to CWD (h2 = 0.611 ± 0.056), and for variation in natural disease progression (h2 = 0.589 ± 0.069); indicating that the majority of the variation in these traits can be explained by genetic differences. Likewise, heritability estimates produced for differential susceptibility to CWD on the liability scale, with adjustment for ascertainment of the case samples (using the weighted mean prevalence) were also high (h2 ≥ 0.857 ± 0.082); only further confirming that the majority of the variation in CWD susceptibility can be explained by genetic differences. To investigate the potential impact of deploying genomic predictions as a management-level decision support tool intended to reduce the prevalence of CWD in farmed U.S. WTD, we used genomic best linear unbiased prediction in conjunction with k-fold cross validation (k = 3; k = 5) and random sampling across 50 iterations for multiple models. Across all model fits and iterations, mean genomic prediction accuracies were high (≥ 0.81). For comparison, we also performed leave-one-out cross-validation; which produced similar results related to genomic prediction accuracy. To further evaluate the utility of a genomic prediction program for CWD management-level decision support, a blind validation was administered by USDAAPHIS. The mean sensitivity of the blind genomic predictions was ≥ 0.87. Collectively, our analyses indicate that WTD breeding programs utilizing genomic predictions for CWD management-level decisions such as genetic improvement through selective breeding, and/or the targeted removal of moderate and highly susceptible WTD, would be expected to reduce the prevalence of CWD.
intcwdsympo.files.wordpress.com/2023/06/final-agenda-with-abstracts.pdf?force_download=true
***> Price of TSE Prion Poker goes up substantially, all you cattle ranchers and such, better pay close attention here...terry
Prion Conference 2023
Transmission of the chronic wasting disease agent from elk to cattle after oronasal exposure
Justin Greenlee, Jifeng Bian, Zoe Lambert, Alexis Frese, and Eric Cassmann Virus and Prion Research Unit, National Animal Disease Center, USDA-ARS, Ames, IA, USA
Aims: The purpose of this study was to determine the susceptibility of cattle to chronic wasting disease agent from elk.
Materials and Methods: Initial studies were conducted in bovinized mice using inoculum derived from elk with various genotypes at codon 132 (MM, LM, LL). Based upon attack rates, inoculum (10% w/v brain homogenate) from an LM132 elk was selected for transmission studies in cattle. At approximately 2 weeks of age, one wild type steer (EE211) and one steer with the E211K polymorphism (EK211) were fed 1 mL of brain homogenate in a quart of milk replacer while another 1 mL was instilled intranasally. The cattle were examined daily for clinical signs for the duration of the experiment. One steer is still under observation at 71 months post-inoculation (mpi).
Results: Inoculum derived from MM132 elk resulted in similar attack rates and incubation periods in mice expressing wild type or K211 bovine PRNP, 35% at 531 days post inoculation (dpi) and 27% at 448 dpi, respectively. Inoculum from LM132 elk had a slightly higher attack rates in mice: 45% (693 dpi) in wild type cattle PRNP and 33% (468) in K211 mice. Inoculum from LL132 elk resulted in the highest attack rate in wild type bovinized mice (53% at 625 dpi), but no K211 mice were affected at >700 days. At approximately 70 mpi, the EK211 genotype steer developed clinical signs suggestive of prion disease, depression, low head carriage, hypersalivation, and ataxia, and was necropsied. Enzyme immunoassay (IDEXX) was positive in brainstem (OD=4.00, but non-detect in retropharyngeal lymph nodes and palatine tonsil. Immunoreactivity was largely limited to the brainstem, midbrain, and cervical spinal cord with a pattern that was primarily glia-associated.
Conclusions: Cattle with the E211K polymorphism are susceptible to the CWD agent after oronasal exposure of 0.2 g of infectious material.
"Cattle with the E211K polymorphism are susceptible to the CWD agent after oronasal exposure of 0.2 g of infectious material."
=====end
Strain characterization of chronic wasting disease in bovine-PrP transgenic mice
Conclusions: Altogether, these results exhibit the diversity of CWD strains present in the panel of CWD isolates and the ability of at least some CWD isolates to infect bovine species. Cattle being one of the most important farming species, this ability represents a potential threat to both animal and human health, and consequently deserves further study.
"Altogether, these results exhibit the diversity of CWD strains present in the panel of CWD isolates and the ability of at least some CWD isolates to infect bovine species. Cattle being one of the most important farming species, this ability represents a potential threat to both animal and human health, and consequently deserves further study."
=====end
prion2023.org/wp-content/uploads/2023/10/Meeting-book-final-version2.pdf
Cattle with the EK211 PRNP polymorphism are susceptible to the H-type bovine spongiform encephalopathy agent from either E211K or wild type donors after oronasal inoculation
Justin J. Greenleea, Eric D. Cassmanna, S. Jo Moorea,b, and M. Heather West Greenleec
aVirus and Prion Research Unit, National Animal Disease Center, ARS, United States Department of Agriculture, Ames, IA, USA; bOak Ridge Institute for Science and Education (ORISE), U.S. Department of Energy, Oak Ridge, TN, US; cDepartment of Biomedical Sciences, Iowa State University College of Veterinary Medicine, Ames, IA, US
Aims: In 2006, a case of H-type bovine spongiform encephalopathy (H-BSE) was reported in a cow with a previously unreported prion protein polymorphism (E211K). The E211K polymorphism is heritable and homologous to the E200K mutation in humans that is the most frequent PRNP mutation associated with familial Creutzfeldt-Jakob disease. Although the prevalence of the E211K polymorphism is low, cattle carrying the K211 allele develop H-type BSE with a rapid onset after experimental inoculation by the intracranial route. The purpose of this study was to investigate whether the agents of H-type BSE or H-type BSE associated with the E211K polymorphism transmit to wild type cattle or cattle with the K211 allele after oronasal exposure.
Material and Methods: Wild type (EE211) or heterozygous (EK211) cattle were oronasally inoculated with the H-BSE agent from either the US 2004 case (wild type donor; n = 3) or from the US 2006 case with the E211K polymorphism (n = 4). Cattle were observed daily throughout the course of the experiment for the development of clinical signs. When signs were noted, animals were euthanized and necropsied. Cattle were confirmed positive for abnormal BSE prions by enzyme immunoassay (EIA; Idexx HerdChek BSE Ag Test), anti-PrP immunohistochemistry (IHC) on brainstem, and microscopic examination for vacuolation.
Results: Three-out-of-four (75%) calves with the EK211 genotype developed clinical signs of H-BSE including inattentiveness, loss of body condition, weakness, ataxia, and muscle fasciculations and were euthanized. Two of the positive EK211 steers received H-BSE US 2004 inoculum (Incubation Period (IP): 59.3 and 72.3 months) while the other positive steer received the E211K H-BSE inoculum (IP: 49.7 months). EIA confirmed that abundant misfolded protein (O.D. 2.57–4.0) in the brainstem, and IHC demonstrated PrPScthroughout the brain. All wild type recipient cattle and a single EK211 steer remained asymptomatic for the duration of the experiment (approximately 7 years post-inoculation) and no abnormal prion protein was detected in these cattle by EIA.
Conclusions: This study demonstrates that the H-type BSE agent is transmissible by the oronasal route. Cattle with the EK211 genotype are oronasally susceptible to small doses of the H-BSE agent from either EK211 or EE211 (wild type) donors. Wild-type EE211 cattle remained asymptomatic for the duration of the experiment with this small dose (0.1 g) of inoculum. These results reinforce the need for ongoing surveillance for classical and atypical BSE to minimize the risk of potentially infectious tissues entering the animal or human food chains.
Funded by: US Department of Agriculture
www.tandfonline.com/doi/full/10.1080/19336896.2022.2091286
fdabse589.blogspot.com/2023/11/food-and-drug-administrations-bse-feed.html
Control of Chronic Wasting Disease OMB Control Number: 0579-0189APHIS-2021-0004 Singeltary Submission
www.regulations.gov/comment/APHIS-2021-0004-0002
downloads.regulations.gov/APHIS-2021-0004-0002/attachment_1.pdf
Docket No. APHIS-2018-0011 Chronic Wasting Disease Herd Certification
www.regulations.gov/document/APHIS-2018-0011-0003
downloads.regulations.gov/APHIS-2018-0011-0003/attachment_1.pdf
APHIS Indemnity Regulations [Docket No. APHIS-2021-0010] RIN 0579-AE65 Singeltary Comment Submission
Comment from Singeltary Sr., Terry
Posted by the Animal and Plant Health Inspection Service on Sep 8, 2022
www.regulations.gov/comment/APHIS-2021-0010-0003
downloads.regulations.gov/APHIS-2021-0010-0003/attachment_1.pdf
Docket No. FDA-2003-D-0432 (formerly 03D-0186) Use of Material from Deer and Elk in Animal Feed
PUBLIC SUBMISSION
Comment from Terry Singeltary Sr.
Posted by the Food and Drug Administration on May 17, 2016 Comment
Docket No. FDA-2003-D-0432 (formerly 03D-0186) Use of Material from Deer and Elk in Animal Feed Singeltary Submission
www.regulations.gov/comment/FDA-2003-D-0432-0011
www.regulations.gov/docket/FDA-2003-D-0432
Singeltary comments;
31 Jan 2015 at 20:14 GMT
Ruminant feed ban for cervids in the United States?
web.archive.org/web/20150722000538/http://www.plosone.org/annotation/listThread.action?root=85351
CHRONIC WASTING DISEASE CWD TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY TSE PRION DISEASE ZOONOSIS, ZOONOTIC
“If CWD in humans is found to be contagious and transmissible among humans, as it is in cervids [57], the spread of the disease within humans might become endemic.”
PART 2. TPWD CHAPTER 65. DIVISION 1. CWD
31 TAC §§65.82, 65.85, 65.88
The Texas Parks and Wildlife Commission in a duly noticed meeting on May 25, 2023 adopted amendments to 31 TAC §§65.82, 65.85, and §65.88, concerning Disease Detection and Response, without changes to the proposed text as published in the April 21, 2023, issue of the Texas Register (48 TexReg 2048). The rules will not be republished.
Currently, there is scientific evidence to suggest that CWD has zoonotic potential; however, no confirmed cases of CWD have been found in humans.
www.sos.texas.gov/texreg/archive/June302023/Adopted%20Rules/31.NATURAL%20RESOURCES%20AND%20CONSERVATION.html#57
17 DETECTION OF CHRONIC WASTING DISEASE PRIONS IN PROCESSED MEATS.
Rebeca Benavente1, Francisca Bravo1,2, Paulina Soto1,2, J. Hunter Reed3, Mitch Lockwood3, Rodrigo Morales1,2
1Department of Neurology, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, USA. 2Universidad Bernardo O’Higgins, Santiago, Chile. 3Texas Parks and Wildlife, Austin, USA
Abstract
The zoonotic potential of chronic wasting disease (CWD) remains unknown. Currently, there are no known natural cases of CWD transmission to humans but increasing evidence suggests that the host range of CWD is not confined only to cervid species. Alarmingly, recent experimental evidence suggests that certain CWD isolates can induce disease in non-human primates. While the CDC strongly recommends determining CWD status in animals prior to consumption, this practice is voluntary. Consequently, it is plausible that a proportion of the cervid meat entering the human food chain may be contaminated with CWD. Of additional concern is that traditional diagnostic techniques used to detect CWD have relatively low sensitivity and are only approved for use in tissues other than those typically ingested by humans. In this study, we analyzed different processed meats derived from a pre-clinical, CWD-positive free-ranging elk. Products tested included filets, sausages, boneless steaks, burgers, ham steaks, seasoned chili meats, and spiced meats. CWD-prion presence in these products were assessed by PMCA using deer and elk substrates. Our results show positive prion detection in all products. To confirm the resilience of CWD-prions to traditional cooking methods, we grilled and boiled the meat products and evaluated them for any remnant PMCA seeding activity. Results confirmed the presence of CWD-prions in these meat products suggesting that infectious particles may still be available to people even after cooking. Our results strongly suggest ongoing human exposure to CWD-prions and raise significant concerns of zoonotic transmission through ingestion of CWD contaminated meat products.
***> Products tested included filets, sausages, boneless steaks, burgers, ham steaks, seasoned chili meats, and spiced meats.
***> CWD-prion presence in these products were assessed by PMCA using deer and elk substrates.
***> Our results show positive prion detection in all products.
***> Results confirmed the presence of CWD-prions in these meat products suggesting that infectious particles may still be available to people even after cooking.
***> Our results strongly suggest ongoing human exposure to CWD-prions and raise significant concerns of zoonotic transmission through ingestion of CWD contaminated meat products.
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9 Carrot plants as potential vectors for CWD transmission.
Paulina Soto1,2, Francisca Bravo-Risi1,2, Claudio Soto1, Rodrigo Morales1,2
1Department of Neurology, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, USA. 2Universidad Bernardo O’Higgins, Santiago, Chile
***> We show that edible plant components can absorb prions from CWD-contaminated soils and transport them to their aerial parts.
***> Our results indicate that edible plants could participate as vectors of CWD transmission
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Transmission of prion infectivity from CWD-infected macaque tissues to rodent models demonstrates the zoonotic potential of chronic wasting disease.
Samia Hannaoui1,2, Ginny Cheng1,2, Wiebke Wemheuer3, Walter Schulz-Schaeffer3, Sabine Gilch1,2, Hermann Schatzl1,2 1University of Calgary, Calgary, Canada. 2Calgary Prion Research Unit, Calgary, Canada. 3Institute of Neuropathology, Medical Faculty, Saarland University, Homburg/Saar, Germany
***> Further passage to cervidized mice revealed transmission with a 100% attack rate.
***> Our findings demonstrate that macaques, considered the best model for the zoonotic potential of prions, were infected upon CWD challenge, including the oral one.
****> The disease manifested as atypical in macaques and initial transgenic mouse transmissions, but with infectivity present at all times, as unveiled in the bank vole model with an unusual tissue tropism.
***> Epidemiologic surveillance of prion disease among cervid hunters and people likely to have consumed venison contaminated with chronic wasting disease
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intcwdsympo.files.wordpress.com/2023/06/final-agenda-with-abstracts.pdf?force_download=true
Transmission of Cervid Prions to Humanized Mice Demonstrates the Zoonotic Potential of CWD
Samia Hannaouia, Irina Zemlyankinaa, Sheng Chun Changa, Maria Immaculata Arifina, Vincent Béringueb, Debbie McKenziec, Hermann M. Schatzla, and Sabine Gilcha
Results: Here, we provide the strongest evidence supporting the zoonotic potential of CWD prions, and their possible phenotype in humans. Inoculation of mice expressing human PrPCwith deer CWD isolates (strains Wisc-1 and 116AG) resulted in atypical clinical manifestations in > 75% of the mice, with myoclonus as leading clinical sign. Most of tg650brain homogenates were positive for seeding activity in RT-QuIC. Clinical disease and presentation was transmissible to tg650 mice and bank voles. Intriguingly, protease-resistant PrP in the brain of tg650 mice resembled that found in a familial human prion disease and was transmissible upon passage. Abnormal PrP aggregates upon infection with Wisc-1 were detectable in thalamus, hypothalamus, and midbrain/pons regions.
Unprecedented in human prion disease, feces of CWD-inoculated tg650 mice harbored prion seeding activity and infectious prions, as shown by inoculation of bank voles and tg650 with fecal homogenates.
Conclusions: This is the first evidence that CWD can infect humans and cause disease with a distinctive clinical presentation, signature, and tropism, which might be transmissible between humans while current diagnostic assays might fail to detect it. These findings have major implications for public health and CWD-management.
www.tandfonline.com/doi/full/10.1080/19336896.2022.2091286 The finding that infectious PrPSc was shed in fecal material of CWD-infected humanized mice and induced clinical disease, different tropism, and typical three banding pattern-PrPres in bank voles that is transmissible upon second passage is highly concerning for public health. The fact that this biochemical signature in bank voles resembles that of the Wisc-1 original deer isolate and is different from that of bvWisc-1, in the migration profile and the glyco-form-ratio, is valid evidence that these results are not a product of contamination in our study. If CWD in humans is found to be contagious and transmissible among humans, as it is in cervids [57], the spread of the disease within humans might become endemic.
Transmission of cervid prions to humanized mice demonstrates the zoonotic potential of CWD
Acta Neuropathol 144, 767–784 (2022). doi.org/10.1007/s00401-022-02482-9
Published
22 August 2022
link.springer.com/article/10.1007/s00401-022-02482-9
Transmission of cervid prions to humanized mice demonstrates the zoonotic potential of CWD
Samia Hannaoui1 · Irina Zemlyankina1 · Sheng Chun Chang1 · Maria Immaculata Arifn1 · Vincent Béringue2 · Debbie McKenzie3 · Hermann M. Schatzl1 · Sabine Gilch1
Received: 24 May 2022 / Revised: 5 August 2022 / Accepted: 7 August 2022
© The Author(s) 2022
Abstract
Prions cause infectious and fatal neurodegenerative diseases in mammals. Chronic wasting disease (CWD), a prion disease of cervids, spreads efficiently among wild and farmed animals. Potential transmission to humans of CWD is a growing concern due to its increasing prevalence. Here, we provide evidence for a zoonotic potential of CWD prions, and its probable signature using mice expressing human prion protein (PrP) as an infection model. Inoculation of these mice with deer CWD isolates resulted in atypical clinical manifestation with prion seeding activity and efficient transmissible infectivity in the brain and, remarkably, in feces, but without classical neuropathological or Western blot appearances of prion diseases. Intriguingly, the protease-resistant PrP in the brain resembled that found in a familial human prion disease and was transmissible upon second passage. Our results suggest that CWD might infect humans, although the transmission barrier is likely higher compared to zoonotic transmission of cattle prions. Notably, our data suggest a different clinical presentation, prion signature, and tissue tropism, which causes challenges for detection by current diagnostic assays. Furthermore, the presence of infectious prions in feces is concerning because if this occurs in humans, it is a source for human-to-human transmission. These findings have strong implications for public health and CWD management.
Keywords Chronic wasting disease · CWD · Zoonotic potential · Prion strains · Zoonotic prions
HIGHLIGHTS OF THIS STUDY
================================
Our results suggest that CWD might infect humans, although the transmission barrier is likely higher compared to zoonotic transmission of cattle prions. Notably, our data suggest a different clinical presentation, prion signature, and tissue tropism, which causes challenges for detection by current diagnostic assays. Furthermore, the presence of infectious prions in feces is concerning because if this occurs in humans, it is a source for human-to-human transmission. These findings have strong implications for public health and CWD management.
In this study, we evaluated the zoonotic potential of CWD using a transgenic mouse model overexpressing human M129-PrPC (tg650 [12]). We inoculated tg650 mice intracerebrally with two deer CWD isolates, Wisc-1 and 116AG [22, 23, 27, 29]. We demonstrate that this transgenic line was susceptible to infection with CWD prions and displayed a distinct leading clinical sign, an atypical PrPSc signature and unusual fecal shedding of infectious prions. Importantly, these prions generated by the human PrP transgenic mice were transmissible upon passage. Our results are the first evidence of a zoonotic risk of CWD when using one of the most common CWD strains, Wisc-1/CWD1 for infection. We demonstrated in a human transgenic mouse model that the species barrier for transmission of CWD to humans is not absolute. The fact that its signature was not typical raises the questions whether CWD would manifest in humans as a subclinical infection, whether it would arise through direct or indirect transmission including an intermediate host, or a silent to uncovered human-to-human transmission, and whether current detection techniques will be suffcient to unveil its presence.
Our findings strongly suggest that CWD should be regarded as an actual public health risk. Here, we use humanized mice to show that CWD prions can cross the species barrier to humans, and remarkably, infectious prions can be excreted in feces.
Our results indicate that if CWD crosses the species-barrier to humans, it is unlikely to resemble the most common forms of human prion diseases with respect to clinical signs, tissue tropism and PrPSc signature. For instance, PrPSc in variable protease-sensitive prionopathy (VPSPr), a sporadic form of human prion disease, and in the genetic form Gerstmann-Sträussler-Scheinker syndrome (GSS) is defined by an atypical PK-resistant PrPSc fragment that is non-glycosylated and truncated at both C- and N-termini, with a molecular weight between 6 and 8 kDa [24, 44–46]. These biochemical features are unique and distinctive from PrPSc (PrP27-30) found in most other human or animal prion disease. The atypical PrPSc signature detected in brain homogenate of tg650 mice #321 (1st passage) and #3063 (2nd passage), and the 7–8 kDa fragment (Figs. 2, 4) are very similar to that of GSS, both in terms of migration profile and the N-terminal cleavage site.
CWD in humans might remain subclinical but with PrPSc deposits in the brain with an unusual morphology that does not resemble the patterns usually seen in different prion diseases (e.g., mouse #328; Fig. 3), clinical with untraceable abnormal PrP (e.g., mouse #327) but still transmissible and uncovered upon subsequent passage (e.g., mouse #3063; Fig. 4), or prions have other reservoirs than the usual ones, hence the presence of infectivity in feces (e.g., mouse #327) suggesting a potential for human-to-human transmission and a real iatrogenic risk that might be unrecognizable.
suggesting a potential for human-to-human transmission and a real iatrogenic risk that might be unrecognizable.
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Supplementary Information The online version contains supplementary material available at
doi.org/10.1007/s00401-022-02482-9
snip...see full text
link.springer.com/article/10.1007/s00401-022-02482-9
link.springer.com/content/pdf/10.1007/s00401-022-02482-9.pdf
Fortuitous generation of a zoonotic cervid prion strain
Manuel Camacho, Xu Qi, Liuting Qing, Sydney Smith, Jieji Hu, Wanyun Tao, Ignazio Cali, Qingzhong Kong. Department of Pathology, Case Western Reserve University, Cleveland, USA
Aims: Whether CWD prions can infect humans remains unclear despite the very substantial scale and long history of human exposure of CWD in many states or provinces of USA and Canada. Multiple in vitro conversion experiments and in vivo animal studies indicate that the CWD-to-human transmission barrier is not unbreakable. A major long-term public health concern on CWD zoonosis is the emergence of highly zoonotic CWD strains. We aim to address the question of whether highly zoonotic CWD strains are possible.
Materials and Methods: We inoculated several sCJD brain samples into cervidized transgenic mice (Tg12), which were intended as negative controls for bioassays of brain tissues from sCJD cases who had potentially been exposed to CWD. Some of the Tg12 mice became infected and their brain tissues were further examined by Western blot as well as serial passages in humanized or cervidized mice.
Results: Passage of sCJDMM1 in transgenic mice expressing elk PrP (Tg12) resulted in a “cervidized” CJD strain that we termed CJDElkPrP. We observed 100% transmission of the original CJDElkPrP in transgenic mice expressing human PrP. We passaged CJDElkPrP two more times in the Tg12 mice. We found that such second and third passage CJDElkPrP prions retained 100% transmission rate in the humanized mice, despite that the natural elk CWD isolates and CJDElkPrP share the same elk PrP sequence. In contrast, we and others found zero or poor transmission of natural elk CWD isolates in humanized mice.
Conclusions: Our data indicate that highly zoonotic cervid prion strains are not only possible but also can retain zoonotic potential after serial passages in cervids, suggesting a very significant and serious long-term risk of CWD zoonosis given that the broad and continuing spread of CWD prions will provide fertile grounds for the emergence of zoonotic CWD strains over time.
Funded by: NIH Grant number: R01NS052319, R01NS088604, R01NS109532
Acknowledgement: We want to thank the National Prion Disease Pathology Surveillance Center and Drs. Allen Jenny and Katherine O'Rourke for providing the sCJD samples and the CWD samples used in this study, respectively
"Our data indicate that highly zoonotic cervid prion strains are not only possible but also can retain zoonotic potential after serial passages in cervids, suggesting a very significant and serious long-term risk of CWD zoonosis given that the broad and continuing spread of CWD prions will provide fertile grounds for the emergence of zoonotic CWD strains over time."
PRION 2023 CONTINUED;
prion2023.org/wp-content/uploads/2023/10/Meeting-book-final-version2.pdf
A probable diagnostic marker for CWD infection in humans
Xu Qi, Liuting Qing, Manuel Camacho, Ignazio Cali, Qingzhong Kong. Department of Pathology, Case Western Reserve University, Cleveland, USA
Aims: Multiple in vitro CWD-seeded human PrP conversion experiments and some animal model studies indicate that the species barrier for CWD to human transmission can be overcome, but whether CWD prion can infect humans in real life remains controversial. The very limited understanding on the likely features of CWD infection in humans and the lack of a reliable diagnostic marker for identification of acquired human CWD cases contribute to this uncertainty. We aim to stablish such a reliable diagnostic marker for CWD infections in humans should they occur.
Materials and Methods: A couple of PrPSc-positive spleens were identified from humanized transgenic mice inoculated with either CWD or sCJDMM1. Prions in these spleens were compared by bioassays in cervidized or humanized transgenic mice. A couple of PrPSc-positive spleens from UK sCJDMM1 patients were also examined similarly as controls with no exposure to CWD.
Results: We have detected two prion-positive spleens in humanized transgenic mice inoculated with some CWD isolates. Such experimentally generated splenic “humanized” CWD prions (termed eHuCWDsp) appear indistinguishable from prions in the brain of sCJDMM1 patients on Western blot. We compared eHuCWDsp with prions in the spleen from humanized mice infected with sCJDMM1 (termed sCJDMM1sp) by bioassays in cervidized or humanized transgenic mice. Significantly, we found that eHuCWDsp can efficiently infect not only the humanized mice but also cervidized transgenic mice, and cervidized mice infected by eHuCWDsp produced PrPSc and brain pathology that are practically identical to those of CWD-infected cervidized mice. In contrast, sCJDMM1sp, similar to prions from sCJDMM1 patient brains, is poorly transmissible in the cervidized mice.
Conclusions: Our data demonstrate that high transmissibility with CWD features of splenic prions in cervidized transgenic mice is unique to acquired human CWD prions, and it may serve as a reliable marker to identify the first acquired human CWD cases.
Funded by: NIH Grant number: R01NS052319, R01NS088604, R01NS109532
Acknowledgement: We want to thank the National Prion Disease Pathology Surveillance Center and Drs. Allen Jenny and Katherine O'Rourke for providing the sCJD samples and the CWD samples used in this study, respectively.
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PRION 2023 CONTINUED;
prion2023.org/wp-content/uploads/2023/10/Meeting-book-final-version2.pdf
Prion 2023 Experimental Oronasal Inoculation of the Chronic Wasting Disease Agent into White Tailed Deer
Author list: Sarah Zurbuchena,b , S. Jo Moorea,b , Jifeng Biana , Eric D. Cassmanna , and Justin J. Greenleea . a. Virus and Prion Research Unit, National Animal Disease Center, ARS, United States Department of Agriculture, Ames, IA, US b. Oak Ridge Institute for Science and Education (ORISE), U.S. Department of Energy, Oak Ridge, TN, United States
Aims: The purpose of this experiment was to determine whether white-tailed deer (WTD) are susceptible to inoculation of chronic wasting disease (CWD) via oronasal exposure.
Materials and methods: Six male, neutered WTD were oronasally inoculated with brainstem material (10% w/v) from a CWD-positive wild-type WTD. The genotypes of five inoculated deer were Q95/G96 (wild-type). One inoculated deer was homozygous S at codon 96 (96SS). Cervidized (Tg12; M132 elk PrP) mice were inoculated with 1% w/v brainstem homogenate from either a 96GG WTD (n=10) or the 96SS WTD (n=10).
Results: All deer developed characteristic clinical signs of CWD including weight loss, regurgitation, and ataxia. The 96SS individual had a prolonged disease course and incubation period compared to the other deer. Western blots of the brainstem on all deer yielded similar molecular profiles. All deer had widespread lymphoid distribution of PrPCWD and neuropathologic lesions associated with transmissible spongiform encephalopathies. Both groups of mice had a 100% attack rate and developed clinical signs, including loss of body condition, ataxia, and loss of righting reflex. Mice inoculated with material from the 96SS deer had a significantly shorter incubation period than mice inoculated with material from 96GG deer (Welch two sample T-test, P<0.05). Serial dilutions of each inocula suggests that differences in incubation period were not due to a greater concentration of PrPCWD in the 96SS inoculum. Molecular profiles from western blot of brain homogenates from mice appeared similar regardless of inoculum and appear similar to those of deer used for inoculum.
Conclusions: This study characterizes the lesions and clinical course of CWD in WTD inoculated in a similar manner to natural conditions. It supports previous findings that 96SS deer have a prolonged disease course. Further, it describes a first pass of inoculum from a 96SS deer in cervidized mice which shortened the incubation period.
Funded by: This research was funded in its entirety by congressionally appropriated funds to the United States Department of Agriculture, Agricultural Research Service. The funders of the work did not influence study design, data collection, analysis, decision to publish, or preparation of the manuscript.
Acknowledgement: We thank Ami Frank and Kevin Hassall for their technical contributions to this project.
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PRION 2023 CONTINUED;
prion2023.org/wp-content/uploads/2023/10/Meeting-book-final-version2.pdf
The detection and decontamination of chronic wasting disease prions during venison processing
Marissa S. Milstein1,2, Marc D. Schwabenlander1,2, Sarah C. Gresch1,2, Manci Li1,2, Stuart Lichtenberg1,2, Rachel Shoemaker1,2, Gage R. Rowden1,2, Jason C. Bartz2,3 , Tiffany M. Wolf2,4, Peter A. Larsen1,2
Presenting author: Tiffany M. Wolf 1 Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, St. Paul, Minnesota, USA 2 Minnesota Center for Prion Research and Outreach, College of Veterinary Medicine, University of Minnesota, St. Paul, Minnesota, USA 3 Department of Medical Microbiology and Immunology, School of Medicine, Creighton University, Omaha, Nebraska, USA 4 Department of Veterinary Population Medicine, College of Veterinary Medicine, University of Minnesota, St. Paul, Minnesota, USA
Aims: There is a growing concern that chronic wasting disease (CWD) prions in venison pose a risk to human health. CWD prions accumulate in infected deer tissues that commonly enter the human food chain through meat processing and consumption. The United States (US) Food and Drug Administration and US Department of Agriculture now formally consider CWD-positive venison unfit for human and animal consumption. Yet, the degree to which prion contamination occurs during routine venison processing is unknown. Here, we use environmental surface swab methods to: a) experimentally test meat processing equipment (i.e., stainless steel knives and polyethylene cutting boards) before and after processing CWD-positive venison and b) test the efficacy of five different disinfectant types (i.e., Dawn dish soap, Virkon-S, Briotech, 10% bleach, and 40% bleach) to determine prion decontamination efficacy.
Materials and Methods: We used a real-time quaking-induced conversion (RT-QuIC) assay to determine CWD infection status of venison and to detect CWD prions in the swabs. We collected three swabs per surface and ran eight technical replicates on RT-QuIC.
Results: CWD prions were detected on all cutting boards (n= 3; replicates= 8/8, 8/8, 8/8 and knives (n= 3; replicates= 8/8, 8/8, 8/8) used in processing CWD-positive venison, but not on those used for CWD-negative venison. After processing CWD-positive venison, allowing the surfaces to dry, and washing the cutting board with Dawn dish soap, we detected CWD prions on the cutting board surface (n= 3; replicates= 8/8, 8/8, 8/8) but not on the knife (n= 3, replicates = 0/8, 0/8, 0/8). Similar patterns were observed with Briotech (cutting board: n= 3; replicates= 7/8, 1/8, 0/8; knife: n= 3; replicates = 0/8, 0/8, 0/8). We did not detect CWD prions on the knives or cutting boards after disinfecting with Virkon-S, 10% bleach, and 40% bleach.
Conclusions: These preliminary results suggest that Dawn dish soap and Briotech do not reliably decontaminate CWD prions from these surfaces. Our data suggest that Virkon-S and various bleach concentrations are more effective in reducing prion contamination of meat processing surfaces; however, surface type may also influence the ability of prions to adsorb to surfaces, preventing complete decontamination. Our results will directly inform best practices to prevent the introduction of CWD prions into the human food chain during venison processing.
Acknowledgement: Funding was provided by the Minnesota Environment and Natural Resources Trust Fund as recommended by the Legislative-Citizen Commission on Minnesota Resources (LCCMR), the Rapid Agriculture Response Fund (#95385/RR257), and the Michigan Department of Natural Resources.
Theme: Animal prion diseases
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Prion 2023 Abstracts
prion2023.org/wp-content/uploads/2023/10/Meeting-book-final-version2.pdf
8. Even though human TSE‐exposure risk through consumption of game from European cervids can be assumed to be minor, if at all existing, no final conclusion can be drawn due to the overall lack of scientific data.
***> In particular the US data do not clearly exclude the possibility of human (sporadic or familial) TSE development due to consumption of venison.
The Working Group thus recognizes a potential risk to consumers if a TSE would be present in European cervids. It might be prudent considering appropriate measures to reduce such a risk, e.g. excluding tissues such as CNS and lymphoid tissues from the human food chain, which would greatly reduce any potential risk for consumers.. However, it is stressed that currently, no data regarding a risk of TSE infections from cervid products are available.
efsa.onlinelibrary.wiley.com/doi/full/10.2903/j.efsa.2018.5132
Research Paper
Cellular prion protein distribution in the vomeronasal organ, parotid, and scent glands of white-tailed deer and mule deer
Anthony Ness, Aradhana Jacob, Kelsey Saboraki, Alicia Otero, Danielle Gushue, Diana Martinez Moreno, Melanie de Peña, Xinli Tang, Judd Aiken, Susan Lingle & Debbie McKenzieORCID Icon show less
Pages 40-57 | Received 03 Feb 2022, Accepted 13 May 2022, Published online: 29 May 2022
Download citation
doi.org/10.1080/19336896.2022.2079888
ABSTRACT
Chronic wasting disease (CWD) is a contagious and fatal transmissible spongiform encephalopathy affecting species of the cervidae family. CWD has an expanding geographic range and complex, poorly understood transmission mechanics. CWD is disproportionately prevalent in wild male mule deer and male white-tailed deer. Sex and species influences on CWD prevalence have been hypothesized to be related to animal behaviours that involve deer facial and body exocrine glands. Understanding CWD transmission potential requires a foundational knowledge of the cellular prion protein (PrPC) in glands associated with cervid behaviours. In this study, we characterized the presence and distribution of PrPC in six integumentary and two non-integumentary tissues of hunter-harvested mule deer (Odocoileus hemionus) and white-tailed deer (O. virginianus). We report that white-tailed deer expressed significantly more PrPC than their mule deer in the parotid, metatarsal, and interdigital glands. Females expressed more PrPC than males in the forehead and preorbital glands. The distribution of PrPC within the integumentary exocrine glands of the face and legs were localized to glandular cells, hair follicles, epidermis, and immune cell infiltrates. All tissues examined expressed sufficient quantities of PrPC to serve as possible sites of prion initial infection, propagation, and shedding.
www.tandfonline.com/doi/full/10.1080/19336896.2022.2079888
ARS RESEARCH Generation of human chronic wasting disease in transgenic mice
Publication Acceptance Date: 9/8/2021
Research Project: Pathobiology, Genetics, and Detection of Transmissible Spongiform Encephalopathies Location: Virus and Prion Research
Title: Generation of human chronic wasting disease in transgenic mice
Author item WANG, ZERUI - Case Western Reserve University (CWRU) item QIN, KEFENG - University Of Chicago item CAMACHO, MANUEL - Case Western Reserve University (CWRU) item SHEN, PINGPING - Case Western Reserve University (CWRU) item YUAN, JUE - Case Western Reserve University (CWRU) item Greenlee, Justin item CUI, LI - Jilin University item KONG, QINGZHONG - Case Western Reserve University (CWRU) item MASTRIANNI, JAMES - University Of Chicago item ZOU, WEN-QUAN - Case Western Reserve University (CWRU)
Submitted to: Acta Neuropathologica Publication Type: Peer Reviewed Journal Publication Acceptance Date: 9/8/2021 Publication Date: N/A Citation: N/A
Interpretive Summary: Prion diseases are invariably fatal neurologic diseases for which there is no known prevention or cure. Chronic wasting disease (CWD) is the prion disease of deer and elk and is present in farmed and free ranging herds throughout North America. To date there is no clear evidence that the CWD agent could be transmitted to humans. This manuscript describes the use of an in vitro technique, cell-free serial protein misfolding cyclic amplification (sPMCA), to generate a CWD prion that is infectious to transgenic mice expressing the human prion protein. This study provides the first evidence that CWD prions may be able to cause misfolding in the human prion protein. This information will impact medical experts and those involved in making policy for farmed cervids and wildlife.
Technical Abstract: Chronic wasting disease (CWD) is a cervid spongiform encephalopathy or prion disease caused by the infectious prion or PrPSc, a misfolded conformer of cellular prion protein (PrPC). It has rapidly spread in North America and also has been found in Asia and Europe. In contrast to the zoonotic mad cow disease that is the first animal prion disease found transmissible to humans, the transmissibility of CWD to humans remains uncertain although most previous studies have suggested that humans may not be susceptible to CWD. Here we report the generation of an infectious human PrPSc by seeding CWD PrPSc in normal human brain PrPC through the in vitro cell-free serial protein misfolding cyclic amplification (sPMCA). Western blotting confirms that the sPMCA-induced proteinase K-resistant PrPSc is a human form, evidenced by a PrP-specific antibody that recognizes human but not cervid PrP. Remarkably, two lines of humanized transgenic (Tg) mice expressing human PrP-129Val/Val (VV) or -129Met/Met (MM) polymorphism develop prion disease at 233 ± 6 (mean ± SE) days post-inoculation (dpi) and 552 ± 27 dpi, respectively, upon intracerebral inoculation with the sPMCA-generated PrPSc. The brain of diseased Tg mice reveals the electrophoretic profile of PrPSc similar to sporadic Creutzfeldt-Jakob disease (sCJD) MM1 or VV2 subtype but different neuropathological patterns. We believe that our study provides the first evidence that CWD PrPSc is able to convert human PrPC into PrPSc in vitro and the CWD-derived human PrPSc mimics atypical sCJD subtypes in humanized Tg mice.
www.ars.usda.gov/research/publications/publication/?seqNo115=382551
''The brain of diseased Tg mice reveals the electrophoretic profile of PrPSc similar to sporadic Creutzfeldt-Jakob disease (sCJD) MM1 or VV2 subtype but different neuropathological patterns.''
''We believe that our study provides the first evidence that CWD PrPSc is able to convert human PrPC into PrPSc in vitro and the CWD-derived human PrPSc mimics atypical sCJD subtypes in humanized Tg mice.''
Published: 26 September 2021
Generation of human chronic wasting disease in transgenic mice
Zerui Wang, Kefeng Qin, Manuel V. Camacho, Ignazio Cali, Jue Yuan, Pingping Shen, Justin Greenlee, Qingzhong Kong, James A. Mastrianni & Wen-Quan Zou
Acta Neuropathologica Communications volume 9, Article number: 158 (2021)
Abstract
Chronic wasting disease (CWD) is a cervid prion disease caused by the accumulation of an infectious misfolded conformer (PrPSc) of cellular prion protein (PrPC). It has been spreading rapidly in North America and also found in Asia and Europe. Although bovine spongiform encephalopathy (i.e. mad cow disease) is the only animal prion disease known to be zoonotic, the transmissibility of CWD to humans remains uncertain. Here we report the generation of the first CWD-derived infectious human PrPSc by elk CWD PrPSc-seeded conversion of PrPC in normal human brain homogenates using in vitro protein misfolding cyclic amplification (PMCA). Western blotting with human PrP selective antibody confirmed that the PMCA-generated protease-resistant PrPSc was derived from the human PrPC substrate. Two lines of humanized transgenic mice expressing human PrP with either Val or Met at the polymorphic codon 129 developed clinical prion disease following intracerebral inoculation with the PMCA-generated CWD-derived human PrPSc. Diseased mice exhibited distinct PrPSc patterns and neuropathological changes in the brain. Our study, using PMCA and animal bioassays, provides the first evidence that CWD PrPSc can cross the species barrier to convert human PrPC into infectious PrPSc that can produce bona fide prion disease when inoculated into humanized transgenic mice.
Snip...
It is worth noting that the annual number of sporadic CJD (sCJD) cases in the USA has increased, with the total number of suspected and confirmed sCJD cases rising from 284 in 2003 to 511 in 2017 (https://www.cdc.gov/prions/cjd/occurrence-transmission.html). The greatly enhanced CJD surveillance and an aging population in the USA certainly contributed to the observed increase in annual sCJD case numbers in recent years, but the possibility cannot be excluded that some of the increased sCJD prevalence is linked to CWD exposure.
In the present study, using serial protein misfolding cyclic amplification (sPMCA) assay we generate PrPSc by seeding CWD prions in normal human brain homogenates. Importantly, we reveal that two lines of humanized Tg mice expressing human PrP-129VV and 129MM develop prion diseases upon intracerebral inoculation of the abnormal PrP generated by sPMCA. We believe that our study provides the first opportunity to dissect the clinical, pathological and biochemical features of the CWD-derived human prion disease in two lines of humanized Tg mice expressing two major human PrP genotypes, respectively.
actaneurocomms.biomedcentral.com/articles/10.1186/s40478-021-01262-y
i thought i might share some news about cwd zoonosis that i got, that i cannot share or post to the public yet, i promised for various reasons, one that it will cause a shit storm for sure, but it was something i really already knew from previous studies, but, i was told that ;
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''As you can imagine, 2 and 5 (especially 5) may raise alarms. The evidence we have for 4 are not as strong or tight as I would like to have. At this point, please do not post any of the points publicly yet, but you can refer to points 1-3 in private discussions and all 5 points when discussing with relevant public officials to highlight the long-term risks of CWD zoonosis.''
====================
so, i figure your as about as official as it gets, and i think this science is extremely important for you to know and to converse about with your officials. it's about to burn a whole in my pocket. this is about as close as it will ever get for cwd zoonosis to be proven in my time, this and what Canada Czub et al found with the Macaques, plus an old study from cjd surveillance unit back that showed cjd and a 9% increase in risk from folks that eat venison, i will post all this below for your files Sir. i remember back in the BSE nvCJD days, from when the first BSE case in bovine was confirmed around 1984 maybe 83, i forget the good vets named that screwed it up first, Carol something, but from 83ish to 95 96 when nvCJD was linked to humans from BSE in cattle, so that took 10 to 15 years. hell, at that rate, especially with Texas and cwd zoonsis, hell, i'll be dead before it's official, if ever, so here ya go Sir. there was a grant study on cwd zoonosis that had been going on for some time, i followed it over the years, then the grant date for said study had expired, so, i thought i would write the good Professor about said study i.e. Professor Kong, CWRU et al. i will post the grant study abstract first, and then after that, what reply i got back, about said study that i was told not to post/publish...
CWD ZOONOSIS GRANT FIRST;
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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
snip...
grantome.com/grant/NIH/R01-NS088604-01A1#panel-abstract
Professor Kongs reply to me just this month about above grant study that has NOT been published in peer reveiw yet...
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Here is a brief summary of our findings:
snip...can't post, made a promise...tss
On Sat, Apr 3, 2021 at 12:19 PM Terry Singeltary <flounder9@verizon.net> wrote:
snip...
end...tss
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CWD ZOONOSIS THE FULL MONTY TO DATE
International Conference on Emerging Diseases, Outbreaks & Case Studies & 16th Annual Meeting on Influenza March 28-29, 2018 | Orlando, USA
Qingzhong Kong
Case Western Reserve University School of Medicine, USA
Zoonotic potential of chronic wasting disease prions from cervids
Chronic wasting disease (CWD) is the prion disease in cervids (mule deer, white-tailed deer, American elk, moose, and reindeer). It has become an epidemic in North America, and it has been detected in the Europe (Norway) since 2016. The widespread CWD and popular hunting and consumption of cervid meat and other products raise serious public health concerns, but questions remain on human susceptibility to CWD prions, especially on the potential difference in zoonotic potential among the various CWD prion strains. We have been working to address this critical question for well over a decade. We used CWD samples from various cervid species to inoculate transgenic mice expressing human or elk prion protein (PrP). We found infectious prions in the spleen or brain in a small fraction of CWD-inoculated transgenic mice expressing human PrP, indicating that humans are not completely resistant to CWD prions; this finding has significant ramifications on the public health impact of CWD prions. The influence of cervid PrP polymorphisms, the prion strain dependence of CWD-to-human transmission barrier, and the characterization of experimental human CWD prions will be discussed.
Speaker Biography Qingzhong Kong has completed his PhD from the University of Massachusetts at Amherst and Post-doctoral studies at Yale University. He is currently an Associate Professor of Pathology, Neurology and Regenerative Medicine. He has published over 50 original research papers in reputable journals (including Science Translational Medicine, JCI, PNAS and Cell Reports) and has been serving as an Editorial Board Member on seven scientific journals. He has multiple research interests, including public health risks of animal prions (CWD of cervids and atypical BSE of cattle), animal modeling of human prion diseases, mechanisms of prion replication and pathogenesis, etiology of sporadic Creutzfeldt-Jacob disease (CJD) in humans, normal cellular PrP in the biology and pathology of multiple brain and peripheral diseases, proteins responsible for the α-cleavage of cellular PrP, as well as gene therapy and DNA vaccination.
qxk2@case.edu
www.alliedacademies.org/conference-abstracts-files/zoonotic-potential-of-chronic-wasting-disease-prions-from.pdf
prionconference.blogspot.com/2018/02/prion-round-table-conference-2018-may.html
prionconference.blogspot.com/
SUNDAY, JULY 25, 2021
North American and Norwegian Chronic Wasting Disease prions exhibit different potential for interspecies transmission and zoonotic risk
''Our data suggest that reindeer and red deer from Norway could be the most transmissible CWD prions to other mammals, whereas North American CWD prions were more prone to generate human prions in vitro.''
chronic-wasting-disease.blogspot.com/2021/07/north-american-and-norwegian-chronic.html
MONDAY, JULY 19, 2021
***> U Calgary researchers at work on a vaccine against a fatal infectious disease affecting deer and potentially people
chronic-wasting-disease.blogspot.com/2021/07/u-calgary-researchers-at-work-on.html
Prion Conference 2018 Abstracts
BSE aka MAD COW DISEASE, was first discovered in 1984, and it took until 1995 to finally admit that BSE was causing nvCJD, the rest there is history, but that science is still evolving i.e. science now shows that indeed atypical L-type BSE, atypical Nor-98 Scrapie, and typical Scrapie are all zoonosis, zoonotic for humans, there from.
HOW long are we going to wait for Chronic Wasting Disease, CWD TSE Prion of Cervid, and zoonosis, zoonotic transmission to humans there from?
Studies have shown since 1994 that humans are susceptible to CWD TSE Prion, so, what's the hold up with making CWD a zoonotic zoonosis disease, the iatrogenic transmissions there from is not waiting for someone to make a decision.
Prion Conference 2018 Abstracts
P190 Human prion disease mortality rates by occurrence of chronic wasting disease in free ranging cervids, United States
Abrams JY (1), Maddox RA (1), Schonberger LB (1), Person MK (1), Appleby BS (2), Belay ED (1)
(1) Centers for Disease Control and Prevention (CDC), National Center for Emerging and Zoonotic Infectious Diseases, Atlanta, GA, USA (2) Case Western Reserve University, National Prion Disease Pathology Surveillance Center (NPDPSC), Cleveland, OH, USA.
Background
Chronic wasting disease (CWD) is a prion disease of deer and elk that has been identified in free ranging cervids in 23 US states. While there is currently no epidemiological evidence for zoonotic transmission through the consumption of contaminated venison, studies suggest the CWD agent can cross the species barrier in experimental models designed to closely mimic humans. We compared rates of human prion disease in states with and without CWD to examine the possibility of undetermined zoonotic transmission.
Methods
Death records from the National Center for Health Statistics, case records from the National Prion Disease Pathology Surveillance Center, and additional state case reports were combined to create a database of human prion disease cases from 2003-2015. Identification of CWD in each state was determined through reports of positive CWD tests by state wildlife agencies. Age- and race-adjusted mortality rates for human prion disease, excluding cases with known etiology, were determined for four categories of states based on CWD occurrence: highly endemic (>16 counties with CWD identified in free-ranging cervids); moderately endemic (3-10 counties with CWD); low endemic (1-2 counties with CWD); and no CWD states. States were counted as having no CWD until the year CWD was first identified. Analyses stratified by age, sex, and time period were also conducted to focus on subgroups for which zoonotic transmission would be more likely to be detected: cases <55 years old, male sex, and the latter half of the study (2010-2015).
Results
Highly endemic states had a higher rate of prion disease mortality compared to non-CWD states (rate ratio [RR]: 1.12, 95% confidence interval [CI] = 1.01 - 1.23), as did low endemic states (RR: 1.15, 95% CI = 1.04 - 1.27). Moderately endemic states did not have an elevated mortality rate (RR: 1.05, 95% CI = 0.93 - 1.17). In age-stratified analyses, prion disease mortality rates among the <55 year old population were elevated for moderately endemic states (RR: 1.57, 95% CI = 1.10 – 2.24) while mortality rates were elevated among those ≥55 for highly endemic states (RR: 1.13, 95% CI = 1.02 - 1.26) and low endemic states (RR: 1.16, 95% CI = 1.04 - 1.29). In other stratified analyses, prion disease mortality rates for males were only elevated for low endemic states (RR: 1.27, 95% CI = 1.10 - 1.48), and none of the categories of CWD-endemic states had elevated mortality rates for the latter time period (2010-2015).
Conclusions
While higher prion disease mortality rates in certain categories of states with CWD in free-ranging cervids were noted, additional stratified analyses did not reveal markedly elevated rates for potentially sensitive subgroups that would be suggestive of zoonotic transmission. Unknown confounding factors or other biases may explain state-by-state differences in prion disease mortality.
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P172 Peripheral Neuropathy in Patients with Prion Disease
Wang H(1), Cohen M(1), Appleby BS(1,2)
(1) University Hospitals Cleveland Medical Center, Cleveland, Ohio (2) National Prion Disease Pathology Surveillance Center, Cleveland, Ohio.
Prion disease is a fatal progressive neurodegenerative disease due to deposition of an abnormal protease-resistant isoform of prion protein. Typical symptoms include rapidly progressive dementia, myoclonus, visual disturbance and hallucinations. Interestingly, in patients with prion disease, the abnormal protein canould also be found in the peripheral nervous system. Case reports of prion deposition in peripheral nerves have been reported. Peripheral nerve involvement is thought to be uncommon; however, little is known about the exact prevalence and features of peripheral neuropathy in patients with prion disease.
We reviewed autopsy-proven prion cases from the National Prion Disease Pathology Surveillance Center that were diagnosed between September 2016 to March 2017. We collected information regarding prion protein diagnosis, demographics, comorbidities, clinical symptoms, physical exam, neuropathology, molecular subtype, genetics lab, brain MRI, image and EMG reports. Our study included 104 patients. Thirteen (12.5%) patients had either subjective symptoms or objective signs of peripheral neuropathy. Among these 13 patients, 3 had other known potential etiologies of peripheral neuropathy such as vitamin B12 deficiency or prior chemotherapy. Among 10 patients that had no other clear etiology, 3 (30%) had familial CJD. The most common sCJD subtype was MV1-2 (30%), followed by MM1-2 (20%). The Majority of cases wasere male (60%). Half of them had exposure to wild game. The most common subjective symptoms were tingling and/or numbness of distal extremities. The most common objective finding was diminished vibratory sensation in the feet. Half of them had an EMG with the findings ranging from fasciculations to axonal polyneuropathy or demyelinating polyneuropathy.
Our study provides an overview of the pattern of peripheral neuropathy in patients with prion disease. Among patients with peripheral neuropathy symptoms or signs, majority has polyneuropathy. It is important to document the baseline frequency of peripheral neuropathy in prion diseases as these symptoms may become important when conducting surveillance for potential novel zoonotic prion diseases.
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P177 PrP plaques in methionine homozygous Creutzfeldt-Jakob disease patients as a potential marker of iatrogenic transmission
Abrams JY (1), Schonberger LB (1), Cali I (2), Cohen Y (2), Blevins JE (2), Maddox RA (1), Belay ED (1), Appleby BS (2), Cohen ML (2)
(1) Centers for Disease Control and Prevention (CDC), National Center for Emerging and Zoonotic Infectious Diseases, Atlanta, GA, USA (2) Case Western Reserve University, National Prion Disease Pathology Surveillance Center (NPDPSC), Cleveland, OH, USA.
Background
Sporadic Creutzfeldt-Jakob disease (CJD) is widely believed to originate from de novo spontaneous conversion of normal prion protein (PrP) to its pathogenic form, but concern remains that some reported sporadic CJD cases may actually be caused by disease transmission via iatrogenic processes. For cases with methionine homozygosity (CJD-MM) at codon 129 of the PRNP gene, recent research has pointed to plaque-like PrP deposition as a potential marker of iatrogenic transmission for a subset of cases. This phenotype is theorized to originate from specific iatrogenic source CJD types that comprise roughly a quarter of known CJD cases.
Methods
We reviewed scientific literature for studies which described PrP plaques among CJD patients with known epidemiological links to iatrogenic transmission (receipt of cadaveric human grown hormone or dura mater), as well as in cases of reported sporadic CJD. The presence and description of plaques, along with CJD classification type and other contextual factors, were used to summarize the current evidence regarding plaques as a potential marker of iatrogenic transmission. In addition, 523 cases of reported sporadic CJD cases in the US from January 2013 through September 2017 were assessed for presence of PrP plaques.
Results
We identified four studies describing 52 total cases of CJD-MM among either dura mater recipients or growth hormone recipients, of which 30 were identified as having PrP plaques. While sporadic cases were not generally described as having plaques, we did identify case reports which described plaques among sporadic MM2 cases as well as case reports of plaques exclusively in white matter among sporadic MM1 cases. Among the 523 reported sporadic CJD cases, 0 of 366 MM1 cases had plaques, 2 of 48 MM2 cases had kuru plaques, and 4 of 109 MM1+2 cases had either kuru plaques or both kuru and florid plaques. Medical chart review of the six reported sporadic CJD cases with plaques did not reveal clinical histories suggestive of potential iatrogenic transmission.
Conclusions
PrP plaques occur much more frequently for iatrogenic CJD-MM cases compared to sporadic CJDMM cases. Plaques may indicate iatrogenic transmission for CJD-MM cases without a type 2 Western blot fragment. The study results suggest the absence of significant misclassifications of iatrogenic CJD as sporadic. To our knowledge, this study is the first to describe grey matter kuru plaques in apparently sporadic CJD-MM patients with a type 2 Western blot fragment.
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P180 Clinico-pathological analysis of human prion diseases in a brain bank series
Ximelis T (1), Aldecoa I (1,2), Molina-Porcel L (1,3), Grau-Rivera O (4), Ferrer I (5), Nos C (6), Gelpi E (1,7), Sánchez-Valle R (1,4)
(1) Neurological Tissue Bank of the Biobanc-Hospital ClÃnic-IDIBAPS, Barcelona, Spain (2) Pathological Service of Hospital ClÃnic de Barcelona, Barcelona, Spain (3) EAIA Trastorns Cognitius, Centre Emili Mira, Parc de Salut Mar, Barcelona, Spain (4) Department of Neurology of Hospital ClÃnic de Barcelona, Barcelona, Spain (5) Institute of Neuropathology, Hospital Universitari de Bellvitge, Hospitalet de Llobregat, Barcelona (6) General subdirectorate of Surveillance and Response to Emergencies in Public Health, Department of Public Health in Catalonia, Barcelona, Spain (7) Institute of Neurology, Medical University of Vienna, Vienna, Austria.
Background and objective:
The Neurological Tissue Bank (NTB) of the Hospital Clínic-Institut d‘Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain is the reference center in Catalonia for the neuropathological study of prion diseases in the region since 2001. The aim of this study is to analyse the characteristics of the confirmed prion diseases registered at the NTB during the last 15 years.
Methods:
We reviewed retrospectively all neuropathologically confirmed cases registered during the period January 2001 to December 2016.
Results:
176 cases (54,3% female, mean age: 67,5 years and age range: 25-86 years) of neuropathological confirmed prion diseases have been studied at the NTB. 152 cases corresponded to sporadic Creutzfeldt-Jakob disease (sCJD), 10 to genetic CJD, 10 to Fatal Familial Insomnia, 2 to GerstmannSträussler-Scheinker disease, and 2 cases to variably protease-sensitive prionopathy (VPSPr). Within sCJD subtypes the MM1 subtype was the most frequent, followed by the VV2 histotype.
Clinical and neuropathological diagnoses agreed in 166 cases (94%). The clinical diagnosis was not accurate in 10 patients with definite prion disease: 1 had a clinical diagnosis of Fronto-temporal dementia (FTD), 1 Niemann-Pick‘s disease, 1 Lewy Body‘s Disease, 2 Alzheimer‘s disease, 1 Cortico-basal syndrome and 2 undetermined dementia. Among patients with VPSPr, 1 had a clinical diagnosis of Amyotrophic lateral sclerosis (ALS) and the other one with FTD.
Concomitant pathologies are frequent in older age groups, mainly AD neuropathological changes were observed in these subjects.
Discussion:
A wide spectrum of human prion diseases have been identified in the NTB being the relative frequencies and main characteristics like other published series. There is a high rate of agreement between clinical and neuropathological diagnoses with prion diseases. These findings show the importance that public health has given to prion diseases during the past 15 years. Continuous surveillance of human prion disease allows identification of new emerging phenotypes. Brain tissue samples from these donors are available to the scientific community. For more information please visit:
www.clinicbiobanc.org/banc-teixits-neurologics/mostres/en_index.html
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P192 Prion amplification techniques for the rapid evaluation of surface decontamination procedures
Bruyere-Ostells L (1), Mayran C (1), Belondrade M (1), Boublik Y (2), Haïk S (3), Fournier-Wirth C (1), Nicot S (1), Bougard D (1)
(1) Pathogenesis and control of chronic infections, Etablissement Français du Sang, Inserm, Université de Montpellier, Montpellier, France. (2) Centre de Recherche en Biologie cellulaire de Montpellier, CNRS, Université de Montpellier, Montpellier, France. (3) Inserm U 1127, CNRS UMR 7225, Sorbonne Universités, UPMC Université Paris 06 UMR S 1127, Institut du Cerveau et de la Moelle épinière, ICM, Paris, France.
Aims:
Transmissible Spongiform Encephalopathies (TSE) or prion diseases are a group of incurable and always fatal neurodegenerative disorders including Creutzfeldt-Jakob diseases (CJD) in humans. These pathologies include sporadic (sCJD), genetic and acquired (variant CJD) forms. By the past, sCJD and vCJD were transmitted by different prion contaminated biological materials to patients resulting in more than 400 iatrogenic cases (iCJD). The atypical nature and the biochemical properties of the infectious agent, formed by abnormal prion protein or PrPTSE, make it particularly resistant to conventional decontamination procedures. In addition, PrPTSE is widely distributed throughout the organism before clinical onset in vCJD and can also be detected in some peripheral tissues in sporadic CJD. Risk of iatrogenic transmission of CJD by contaminated medical device remains thus a concern for healthcare facilities. Bioassay is the gold standard method to evaluate the efficacy of prion decontamination procedures but is time-consuming and expensive. Here, we propose to compare in vitro prion amplification techniques: Protein Misfolding Cyclic Amplification (PMCA) and Real-Time Quaking Induced Conversion (RT-QuIC) for the detection of residual prions on surface after decontamination.
Methods:
Stainless steel wires, by mimicking the surface of surgical instruments, were proposed as a carrier model of prions for inactivation studies. To determine the sensitivity of the two amplification techniques on wires (Surf-PMCA and Surf-QuIC), steel wires were therefore contaminated with serial dilutions of brain homogenates (BH) from a 263k infected hamster and from a patient with sCJD (MM1 subtype). We then compared the different standard decontamination procedures including partially and fully efficient treatments by detecting the residual seeding activity on 263K and sCJD contaminated wires. We completed our study by the evaluation of marketed reagents endorsed for prion decontamination.
Results:
The two amplification techniques can detect minute quantities of PrPTSE adsorbed onto a single wire. 8/8 wires contaminated with a 10-6 dilution of 263k BH and 1/6 with the 10-8 dilution are positive with Surf-PMCA. Similar performances were obtained with Surf-QuIC on 263K: 10/16 wires contaminated with 10-6 dilution and 1/8 wires contaminated with 10-8 dilution are positive. Regarding the human sCJD-MM1 prion, Surf-QuIC allows us to detect 16/16 wires contaminated with 10-6 dilutions and 14/16 with 10-7 . Results obtained after decontamination treatments are very similar between 263K and sCJD prions. Efficiency of marketed treatments to remove prions is lower than expected.
Conclusions:
Surf-PMCA and Surf-QuIC are very sensitive methods for the detection of prions on wires and could be applied to prion decontamination studies for rapid evaluation of new treatments. Sodium hypochlorite is the only product to efficiently remove seeding activity of both 263K and sCJD prions.
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WA2 Oral transmission of CWD into Cynomolgus macaques: signs of atypical disease, prion conversion and infectivity in macaques and bio-assayed transgenic mice
Schatzl HM (1, 2), Hannaoui S (1, 2), Cheng Y-C (1, 2), Gilch S (1, 2), Beekes M (3), SchulzSchaeffer W (4), Stahl-Hennig C (5) and Czub S (2, 6)
(1) University of Calgary, Calgary Prion Research Unit, Calgary, Canada (2) University of Calgary, Faculty of Veterinary Medicine, Calgary, Canada, (3) Robert Koch Institute, Berlin, Germany, (4) University of Homburg/Saar, Homburg, Germany, (5) German Primate Center, Goettingen, Germany, (6) Canadian Food Inspection Agency (CFIA), Lethbridge, Canada.
To date, BSE is the only example of interspecies transmission of an animal prion disease into humans. The potential zoonotic transmission of CWD is an alarming issue and was addressed by many groups using a variety of in vitro and in vivo experimental systems. Evidence from these studies indicated a substantial, if not absolute, species barrier, aligning with the absence of epidemiological evidence suggesting transmission into humans. Studies in non-human primates were not conclusive so far, with oral transmission into new-world monkeys and no transmission into old-world monkeys. Our consortium has challenged 18 Cynomolgus macaques with characterized CWD material, focusing on oral transmission with muscle tissue. Some macaques have orally received a total of 5 kg of muscle material over a period of 2 years. After 5-7 years of incubation time some animals showed clinical symptoms indicative of prion disease, and prion neuropathology and PrPSc deposition were found in spinal cord and brain of euthanized animals. PrPSc in immunoblot was weakly detected in some spinal cord materials and various tissues tested positive in RT-QuIC, including lymph node and spleen homogenates. To prove prion infectivity in the macaque tissues, we have intracerebrally inoculated 2 lines of transgenic mice, expressing either elk or human PrP. At least 3 TgElk mice, receiving tissues from 2 different macaques, showed clinical signs of a progressive prion disease and brains were positive in immunoblot and RT-QuIC. Tissues (brain, spinal cord and spleen) from these and preclinical mice are currently tested using various read-outs and by second passage in mice. Transgenic mice expressing human PrP were so far negative for clear clinical prion disease (some mice >300 days p.i.). In parallel, the same macaque materials are inoculated into bank voles. Taken together, there is strong evidence of transmissibility of CWD orally into macaques and from macaque tissues into transgenic mouse models, although with an incomplete attack rate. The clinical and pathological presentation in macaques was mostly atypical, with a strong emphasis on spinal cord pathology. Our ongoing studies will show whether the transmission of CWD into macaques and passage in transgenic mice represents a form of non-adaptive prion amplification, and whether macaque-adapted prions have the potential to infect mice expressing human PrP. The notion that CWD can be transmitted orally into both new-world and old-world non-human primates asks for a careful reevaluation of the zoonotic risk of CWD.
See also poster P103
***> The notion that CWD can be transmitted orally into both new-world and old-world non-human primates asks for a careful reevaluation of the zoonotic risk of CWD.
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WA16 Monitoring Potential CWD Transmission to Humans
Belay ED
Centers for Disease Control and Prevention (CDC), National Center for Emerging and Zoonotic Infectious Diseases, Atlanta, GA, USA.
The spread of chronic wasting disease (CWD) in animals has raised concerns about increasing human exposure to the CWD agent via hunting and venison consumption, potentially facilitating CWD transmission to humans. Several studies have explored this possibility, including limited epidemiologic studies, in vitro experiments, and laboratory studies using various types of animal models. Most human exposures to the CWD agent in the United States would be expected to occur in association with deer and elk hunting in CWD-endemic areas. The Centers for Disease Control and Prevention (CDC) collaborated with state health departments in Colorado, Wisconsin, and Wyoming to identify persons at risk of CWD exposure and to monitor their vital status over time. Databases were established of persons who hunted in Colorado and Wyoming and those who reported consumption of venison from deer that later tested positive in Wisconsin. Information from the databases is periodically cross-checked with mortality data to determine the vital status and causes of death for deceased persons. Long-term follow-up of these hunters is needed to assess their risk of development of a prion disease linked to CWD exposure.
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P166 Characterization of CJD strain profiles in venison consumers and non-consumers from Alberta and Saskatchewan
Stephanie Booth (1,2), Lise Lamoureux (1), Debra Sorensen (1), Jennifer L. Myskiw (1,2), Megan Klassen (1,2), Michael Coulthart (3), Valerie Sim (4)
(1) Zoonotic Diseases and Special Pathogens, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg (2) Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg (3) Canadian CJD Surveillance System, Public Health Agency of Canada, Ottawa (4) Division of Neurology, Department of Medicine Centre for Prions and Protein Folding Diseases, University of Alberta, Edmonton.
Chronic wasting disease (CWD) is spreading rapidly through wild cervid populations in the Canadian provinces of Alberta and Saskatchewan. While this has implications for tourism and hunting, there is also concern over possible zoonotic transmission to humans who eat venison from infected deer. Whilst there is no evidence of any human cases of CWD to date, the Canadian CJD Surveillance System (CJDSS) in Canada is staying vigilant. When variant CJD occurred following exposure to BSE, the unique biochemical fingerprint of the pathologic PrP enabled a causal link to be confirmed. However, we cannot be sure what phenotype human CWD prions would present with, or indeed, whether this would be distinct from that see in sporadic CJD. Therefore we are undertaking a systematic analysis of the molecular diversity of CJD cases of individuals who resided in Alberta and Saskatchewan at their time of death comparing venison consumers and non-consumers, using a variety of clinical, imaging, pathological and biochemical markers. Our initial objective is to develop novel biochemical methodologies that will extend the baseline glycoform and genetic polymorphism typing that is already completed by the CJDSS. Firstly, we are reviewing MRI, EEG and pathology information from over 40 cases of CJD to select clinically affected areas for further investigation. Biochemical analysis will include assessment of the levels of protease sensitive and resistant prion protein, glycoform typing using 2D gel electrophoresis, testing seeding capabilities and kinetics of aggregation by quaking-induced conversion, and determining prion oligomer size distributions with asymmetric flow field fractionation with in-line light scattering. Progress and preliminary data will be presented. Ultimately, we intend to further define the relationship between PrP structure and disease phenotype and establish a baseline for the identification of future atypical CJD cases that may arise as a result of exposure to CWD.
=====
Source Prion Conference 2018 Abstracts
transmissiblespongiformencephalopathy.blogspot.com/2018/05/prion-2018-may-22-25-2018-santiago-de.html
chronic-wasting-disease.blogspot.com/2018/07/oral-transmission-of-cwd-into.html
prionconference.blogspot.com/2018/
Volume 24, Number 8—August 2018
Research Susceptibility of Human Prion Protein to Conversion by Chronic Wasting Disease Prions
Marcelo A. BarriaComments to Author , Adriana Libori, Gordon Mitchell, and Mark W. Head Author affiliations: National CJD Research and Surveillance Unit, University of Edinburgh, Edinburgh, Scotland, UK (M.A. Barria, A. Libori, M.W. Head); National and OIE Reference Laboratory for Scrapie and CWD, Canadian Food Inspection Agency, Ottawa, Ontario, Canada (G. Mitchell)
Abstract Chronic wasting disease (CWD) is a contagious and fatal neurodegenerative disease and a serious animal health issue for deer and elk in North America. The identification of the first cases of CWD among free-ranging reindeer and moose in Europe brings back into focus the unresolved issue of whether CWD can be zoonotic like bovine spongiform encephalopathy. We used a cell-free seeded protein misfolding assay to determine whether CWD prions from elk, white-tailed deer, and reindeer in North America can convert the human prion protein to the disease-associated form. We found that prions can convert, but the efficiency of conversion is affected by polymorphic variation in the cervid and human prion protein genes. In view of the similarity of reindeer, elk, and white-tailed deer in North America to reindeer, red deer, and roe deer, respectively, in Europe, a more comprehensive and thorough assessment of the zoonotic potential of CWD might be warranted.
snip...
Discussion Characterization of the transmission properties of CWD and evaluation of their zoonotic potential are important for public health purposes. Given that CWD affects several members of the family Cervidae, it seems reasonable to consider whether the zoonotic potential of CWD prions could be affected by factors such as CWD strain, cervid species, geographic location, and Prnp–PRNP polymorphic variation. We have previously used an in vitro conversion assay (PMCA) to investigate the susceptibility of the human PrP to conversion to its disease-associated form by several animal prion diseases, including CWD (15,16,22). The sensitivity of our molecular model for the detection of zoonotic conversion depends on the combination of 1) the action of proteinase K to degrade the abundant human PrPC that constitutes the substrate while only N terminally truncating any human PrPres produced and 2) the presence of the 3F4 epitope on human but not cervid PrP. In effect, this degree of sensitivity means that any human PrPres formed during the PMCA reaction can be detected down to the limit of Western blot sensitivity. In contrast, if other antibodies that detect both cervid and human PrP are used, such as 6H4, then newly formed human PrPres must be detected as a measurable increase in PrPres over the amount remaining in the reaction product from the cervid seed. Although best known for the efficient amplification of prions in research and diagnostic contexts, the variation of the PMCA method employed in our study is optimized for the definitive detection of zoonotic reaction products of inherently inefficient conversion reactions conducted across species barriers. By using this system, we previously made and reported the novel observation that elk CWD prions could convert human PrPC from human brain and could also convert recombinant human PrPC expressed in transgenic mice and eukaryotic cell cultures (15).
A previous publication suggested that mule deer PrPSc was unable to convert humanized transgenic substrate in PMCA assays (23) and required a further step of in vitro conditioning in deer substrate PMCA before it was able to cross the deer–human molecular barrier (24). However, prions from other species, such as elk (15) and reindeer affected by CWD, appear to be compatible with the human protein in a single round of amplification (as shown in our study). These observations suggest that different deer species affected by CWD could present differing degrees of the olecular compatibility with the normal form of human PrP.
The contribution of the polymorphism at codon 129 of the human PrP gene has been extensively studied and is recognized as a risk factor for Creutzfeldt-Jakob disease (4). In cervids, the equivalent codon corresponds to the position 132 encoding methionine or leucine. This polymorphism in the elk gene has been shown to play an important role in CWD susceptibility (25,26). We have investigated the effect of this cervid Prnp polymorphism on the conversion of the humanized transgenic substrate according to the variation in the equivalent PRNP codon 129 polymorphism. Interestingly, only the homologs methionine homozygous seed–substrate reactions could readily convert the human PrP, whereas the heterozygous elk PrPSc was unable to do so, even though comparable amounts of PrPres were used to seed the reaction. In addition, we observed only low levels of human PrPres formation in the reactions seeded with the homozygous methionine (132 MM) and the heterozygous (132 ML) seeds incubated with the other 2 human polymorphic substrates (129 MV and 129 VV). The presence of the amino acid leucine at position 132 of the elk Prnp gene has been attributed to a lower degree of prion conversion compared with methionine on the basis of experiments in mice made transgenic for these polymorphic variants (26). Considering the differences observed for the amplification of the homozygous human methionine substrate by the 2 polymorphic elk seeds (MM and ML), reappraisal of the susceptibility of human PrPC by the full range of cervid polymorphic variants affected by CWD would be warranted.
In light of the recent identification of the first cases of CWD in Europe in a free-ranging reindeer (R. tarandus) in Norway (2), we also decided to evaluate the in vitro conversion potential of CWD in 2 experimentally infected reindeer (18). Formation of human PrPres was readily detectable after a single round of PMCA, and in all 3 humanized polymorphic substrates (MM, MV, and VV). This finding suggests that CWD prions from reindeer could be more compatible with human PrPC generally and might therefore present a greater risk for zoonosis than, for example, CWD prions from white-tailed deer. A more comprehensive comparison of CWD in the affected species, coupled with the polymorphic variations in the human and deer PRNP–Prnp genes, in vivo and in vitro, will be required before firm conclusions can be drawn. Analysis of the Prnp sequence of the CWD reindeer in Norway was reported to be identical to the specimens used in our study (2). This finding raises the possibility of a direct comparison of zoonotic potential between CWD acquired in the wild and that produced in a controlled laboratory setting. (Table).
The prion hypothesis proposes that direct molecular interaction between PrPSc and PrPC is necessary for conversion and prion replication. Accordingly, polymorphic variants of the PrP of host and agent might play a role in determining compatibility and potential zoonotic risk. In this study, we have examined the capacity of the human PrPC to support in vitro conversion by elk, white-tailed deer, and reindeer CWD PrPSc. Our data confirm that elk CWD prions can convert the human PrPC, at least in vitro, and show that the homologous PRNP polymorphisms at codon 129 and 132 in humans and cervids affect conversion efficiency. Other species affected by CWD, particularly caribou or reindeer, also seem able to convert the human PrP. It will be important to determine whether other polymorphic variants found in other CWD-affected Cervidae or perhaps other factors (17) exert similar effects on the ability to convert human PrP and thus affect their zoonotic potential.
Dr. Barria is a research scientist working at the National CJD Research and Surveillance Unit, University of Edinburgh. His research has focused on understanding the molecular basis of a group of fatal neurologic disorders called prion diseases.
Acknowledgments We thank Aru Balachandran for originally providing cervid brain tissues, Abigail Diack and Jean Manson for providing mouse brain tissue, and James Ironside for his critical reading of the manuscript at an early stage.
This report is independent research commissioned and funded by the United Kingdom’s Department of Health Policy Research Programme and the Government of Scotland. The views expressed in this publication are those of the authors and not necessarily those of the Department of Health or the Government of Scotland.
Author contributions: The study was conceived and designed by M.A.B. and M.W.H. The experiments were conducted by M.A.B. and A.L. Chronic wasting disease brain specimens were provided by G.M. The manuscript was written by M.A.B. and M.W.H. All authors contributed to the editing and revision of the manuscript.
wwwnc.cdc.gov/eid/article/24/8/16-1888_article
www.ed.ac.uk/clinical-brain-sciences/news/news-jul-dec-2018/cwd-prions-human-conversion
Prion 2017 Conference Abstracts
First evidence of intracranial and peroral transmission of Chronic Wasting Disease (CWD) into Cynomolgus macaques: a work in progress
Stefanie Czub1, Walter Schulz-Schaeffer2, Christiane Stahl-Hennig3, Michael Beekes4, Hermann Schaetzl5 and Dirk Motzkus6 1 University of Calgary Faculty of Veterinary Medicine/Canadian Food Inspection Agency; 2Universitatsklinikum des Saarlandes und Medizinische Fakultat der Universitat des Saarlandes; 3 Deutsches Primaten Zentrum/Goettingen; 4 Robert-Koch-Institut Berlin; 5 University of Calgary Faculty of Veterinary Medicine; 6 presently: Boehringer Ingelheim Veterinary Research Center; previously: Deutsches Primaten Zentrum/Goettingen
This is a progress report of a project which started in 2009.
21 cynomolgus macaques were challenged with characterized CWD material from white-tailed deer (WTD) or elk by intracerebral (ic), oral, and skin exposure routes. Additional blood transfusion experiments are supposed to assess the CWD contamination risk of human blood product. Challenge materials originated from symptomatic cervids for ic, skin scarification and partially per oral routes (WTD brain). Challenge material for feeding of muscle derived from preclinical WTD and from preclinical macaques for blood transfusion experiments. We have confirmed that the CWD challenge material contained at least two different CWD agents (brain material) as well as CWD prions in muscle-associated nerves. Here we present first data on a group of animals either challenged ic with steel wires or per orally and sacrificed with incubation times ranging from 4.5 to 6.9 years at postmortem. Three animals displayed signs of mild clinical disease, including anxiety, apathy, ataxia and/or tremor. In four animals wasting was observed, two of those had confirmed diabetes. All animals have variable signs of prion neuropathology in spinal cords and brains and by supersensitive IHC, reaction was detected in spinal cord segments of all animals. Protein misfolding cyclic amplification (PMCA), real-time quaking-induced conversion (RT-QuiC) and PET-blot assays to further substantiate these findings are on the way, as well as bioassays in bank voles and transgenic mice. At present, a total of 10 animals are sacrificed and read-outs are ongoing. Preclinical incubation of the remaining macaques covers a range from 6.4 to 7.10 years. Based on the species barrier and an incubation time of > 5 years for BSE in macaques and about 10 years for scrapie in macaques, we expected an onset of clinical disease beyond 6 years post inoculation.
PRION 2017 DECIPHERING NEURODEGENERATIVE DISORDERS ABSTRACTS REFERENCE
aabb.confex.com/aabb/2018/mediafile/Handout/Session2756/TU1-3.pdf
8. Even though human TSE‐exposure risk through consumption of game from European cervids can be assumed to be minor, if at all existing, no final conclusion can be drawn due to the overall lack of scientific data. In particular the US data do not clearly exclude the possibility of human (sporadic or familial) TSE development due to consumption of venison. The Working Group thus recognizes a potential risk to consumers if a TSE would be present in European cervids. It might be prudent considering appropriate measures to reduce such a risk, e.g. excluding tissues such as CNS and lymphoid tissues from the human food chain, which would greatly reduce any potential risk for consumers. However, it is stressed that currently, no data regarding a risk of TSE infections from cervid products are available.
efsa.onlinelibrary.wiley.com/doi/full/10.2903/j.efsa.2018.5132
SATURDAY, FEBRUARY 23, 2019
Chronic Wasting Disease CWD TSE Prion and THE FEAST 2003 CDC an updated review of the science 2019
chronic-wasting-disease.blogspot.com/2019/02/chronic-wasting-disease-cwd-tse-prion.html
TUESDAY, NOVEMBER 04, 2014
Six-year follow-up of a point-source exposure to CWD contaminated venison in an Upstate New York community: risk behaviours and health outcomes 2005–2011 Authors, though, acknowledged the study was limited in geography and sample size and so it couldn't draw a conclusion about the risk to humans. They recommended more study. Dr. Ermias Belay was the report's principal author but he said New York and Oneida County officials are following the proper course by not launching a study. "There's really nothing to monitor presently. No one's sick," Belay said, noting the disease's incubation period in deer and elk is measured in years. "
chronic-wasting-disease.blogspot.com/2014/11/six-year-follow-up-of-point-source.html
Transmission Studies Mule deer transmissions of CWD were by intracerebral inoculation and compared with natural cases {the following was written but with a single line marked through it ''first passage (by this route)}....TSS resulted in a more rapidly progressive clinical disease with repeated episodes of synocopy ending in coma. One control animal became affected, it is believed through contamination of inoculum (?saline). Further CWD transmissions were carried out by Dick Marsh into ferret, mink and squirrel monkey. Transmission occurred in ALL of these species with the shortest incubation period in the ferret.
snip....
web.archive.org/web/20090506002237/http://www..bseinquiry.gov.uk/files/mb/m11b/tab01.pdf
Prion Infectivity in Fat of Deer with Chronic Wasting Disease▿
Brent Race#, Kimberly Meade-White#, Richard Race and Bruce Chesebro* + Author Affiliations In mice, prion infectivity was recently detected in fat. Since ruminant fat is consumed by humans and fed to animals, we determined infectivity titers in fat from two CWD-infected deer. Deer fat devoid of muscle contained low levels of CWD infectivity and might be a risk factor for prion infection of other species.
jvi.asm.org/content/83/18/9608.full Prions in Skeletal Muscles of Deer with Chronic Wasting Disease Here bioassays in transgenic mice expressing cervid prion protein revealed the presence of infectious prions in skeletal muscles of CWD-infected deer, demonstrating that humans consuming or handling meat from CWD-infected deer are at risk to prion exposure.
science.sciencemag.org/content/311/5764/1117..long
*** now, let’s see what the authors said about this casual link, personal communications years ago, and then the latest on the zoonotic potential from CWD to humans from the TOKYO PRION 2016 CONFERENCE.
see where it is stated NO STRONG evidence. so, does this mean there IS casual evidence
?
“Our conclusion stating that we found no strong evidence of CWD transmission to humans”
From: TSS Subject: CWD aka MAD DEER/ELK TO HUMANS
Date: September 30, 2002 at 7:06 am PST
From: "Belay, Ermias"
To: Cc: "Race, Richard (NIH)" ; ; "Belay, Ermias"
Sent: Monday, September 30, 2002 9:22 AM
Subject: RE: TO CDC AND NIH - PUB MED- 3 MORE DEATHS - CWD - YOUNG HUNTERS
Dear Sir/Madam, In the Archives of Neurology you quoted (the abstract of which was attached to your email), we did not say CWD in humans will present like variant CJD.. That assumption would be wrong. I encourage you to read the whole article and call me if you have questions or need more clarification (phone: 404-639-3091).
Also, we do not claim that "no-one has ever been infected with prion disease from eating venison." Our conclusion stating that we found no strong evidence of CWD transmission to humans in the article you quoted or in any other forum is limited to the patients we investigated.
Ermias Belay, M.D. Centers for Disease Control and Prevention
-----Original Message----- From:
Sent: Sunday, September 29, 2002 10:15 AM
To: rr26k@nih.gov; rrace@niaid.nih.gov; ebb8@CDC.GOV
Subject: TO CDC AND NIH - PUB MED- 3 MORE DEATHS - CWD - YOUNG HUNTERS
Sunday, November 10, 2002 6:26 PM .......snip........end..............TSS
Thursday, April 03, 2008
A prion disease of cervids: Chronic wasting disease 2008 1: Vet Res. 2008 Apr 3;39(4):41 A prion disease of cervids: Chronic wasting disease Sigurdson CJ.
snip... *** twenty-seven CJD patients who regularly consumed venison were reported to the Surveillance Center***,
snip... full text ;
chronic-wasting-disease.blogspot.com/2008/04/prion-disease-of-cervids-chronic.html
> However, to date, no CWD infections have been reported in people.
sporadic, spontaneous CJD, 85%+ of all human TSE, did not just happen. never in scientific literature has this been proven. if one looks up the word sporadic or spontaneous at pubmed, you will get a laundry list of disease that are classified in such a way;
sporadic = 54,983 hits
www.ncbi.nlm.nih.gov/pubmed/?term=sporadic
spontaneous = 325,650 hits
www.ncbi.nlm.nih.gov/pubmed/?term=spontaneous
key word here is 'reported'. science has shown that CWD in humans will look like sporadic CJD.
SO, how can one assume that CWD has not already transmitted to humans? they can't, and it's as simple as that. from all recorded science to date, CWD has already transmitted to humans, and it's being misdiagnosed as sporadic CJD. ...terry
*** LOOKING FOR CWD IN HUMANS AS nvCJD or as an ATYPICAL CJD, LOOKING IN ALL THE WRONG PLACES $$$ ***
> However, to date, no CWD infections have been reported in people. key word here is ‘reported’. science has shown that CWD in humans will look like sporadic CJD. SO, how can one assume that CWD has not already transmitted to humans? they can’t, and it’s as simple as that. from all recorded science to date, CWD has already transmitted to humans, and it’s being misdiagnosed as sporadic CJD. …terry
*** 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).***
www.tandfonline.com/doi/full/10.4161/pri.28124?src=recsys
www.tandfonline.com/doi/pdf/10.4161/pri.28124?needAccess=true
wwwnc.cdc.gov/eid/article/20/1/13-0858_article
CWD TSE PRION AND ZOONOTIC, ZOONOSIS, FACTORS
Subject: Re: DEER SPONGIFORM ENCEPHALOPATHY SURVEY & HOUND STUDY
Date: Fri, 18 Oct 2002 23:12:22 +0100
From: Steve Dealler
Reply-To: Bovine Spongiform Encephalopathy Organization: Netscape Online member
To: BSE-L@ References:
Dear Terry,
An excellent piece of review as this literature is desperately difficult to get back from Government sites.
What happened with the deer was that an association between deer meat eating and sporadic CJD was found in about 1993. The evidence was not great but did not disappear after several years of asking CJD cases what they had eaten. I think that the work into deer disease largely stopped because it was not helpful to the UK industry...and no specific cases were reported. Well, if you dont look adequately like they are in USA currenly then you wont find any!
Steve Dealler
====
caninespongiformencephalopathy.blogspot.com/2010/03/canine-spongiform-encephalopathy-aka.html
''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).''
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 ;
web.archive.org/web/20090506050043/http://www.bseinquiry.gov.uk/files/yb/1994/08/00004001.pdf
web.archive.org/web/20090506050007/http://www.bseinquiry.gov.uk/files/yb/1994/10/00003001.pdf
web.archive.org/web/20090506050244/http://www.bseinquiry.gov.uk/files/yb/1994/07/00001001.pdf
Stephen Dealler is a consultant medical microbiologist deal@airtime.co.uk
BSE Inquiry Steve Dealler
Management In Confidence
BSE: Private Submission of Bovine Brain Dealler
snip...see full text;
MONDAY, FEBRUARY 25, 2019
***> MAD DOGS AND ENGLISHMEN BSE, SCRAPIE, CWD, CJD, TSE PRION A REVIEW 2019
bseinquiry.blogspot.com/2019/02/mad-dogs-and-englishmen-bse-scrapie-cwd.html
***> ''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).''
***> In conclusion, sensory symptoms and loss of reflexes in Gerstmann-Sträussler-Scheinker syndrome can be explained by neuropathological changes in the spinal cord. We conclude that the sensory symptoms and loss of lower limb reflexes in Gerstmann-Sträussler-Scheinker syndrome is due to pathology in the caudal spinal cord. <***
***> The clinical and pathological presentation in macaques was mostly atypical, with a strong emphasis on spinal cord pathology.<***
***> The notion that CWD can be transmitted orally into both new-world and old-world non-human primates asks for a careful reevaluation of the zoonotic risk of CWD. <***
***> All animals have variable signs of prion neuropathology in spinal cords and brains and by supersensitive IHC, reaction was detected in spinal cord segments of all animals.<***
***> In particular the US data do not clearly exclude the possibility of human (sporadic or familial) TSE development due to consumption of venison. The Working Group thus recognizes a potential risk to consumers if a TSE would be present in European cervids.'' Scientific opinion on chronic wasting disease (II) <***
familialcjdtseprion.blogspot.com/2019/02/cwd-gss-tse-prion-spinal-cord-confucius.html
***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.***
Even if the prevailing view is that sporadic CJD is due to the spontaneous formation of CJD prions, it remains possible that its apparent sporadic nature may, at least in part, result from our limited capacity to identify an environmental origin.
www.nature.com/articles/srep11573
cwd scrapie pigs oral routes, oh my!
***> However, at 51 months of incubation or greater, 5 animals were positive by one or more diagnostic methods. Furthermore, positive bioassay results were obtained from all inoculated groups (oral and intracranial; market weight and end of study) suggesting that swine are potential hosts for the agent of scrapie. <***
>*** Although the current U.S. feed ban is based on keeping tissues from TSE infected cattle from contaminating animal feed, swine rations in the U.S. could contain animal derived components including materials from scrapie infected sheep and goats. These results indicating the susceptibility of pigs to sheep scrapie, coupled with the limitations of the current feed ban, indicates that a revision of the feed ban may be necessary to protect swine production and potentially human health. <***
***> Results: PrPSc was not detected by EIA and IHC in any RPLNs. All tonsils and MLNs were negative by IHC, though the MLN from one pig in the oral <6 month group was positive by EIA. PrPSc was detected by QuIC in at least one of the lymphoid tissues examined in 5/6 pigs in the intracranial <6 months group, 6/7 intracranial >6 months group, 5/6 pigs in the oral <6 months group, and 4/6 oral >6 months group. Overall, the MLN was positive in 14/19 (74%) of samples examined, the RPLN in 8/18 (44%), and the tonsil in 10/25 (40%).
***> Conclusions: This study demonstrates that PrPSc accumulates in lymphoid tissues from pigs challenged intracranially or orally with the CWD agent, and can be detected as early as 4 months after challenge. CWD-infected pigs rarely develop clinical disease and if they do, they do so after a long incubation period. This raises the possibility that CWD-infected pigs could shed prions into their environment long before they develop clinical disease. Furthermore, lymphoid tissues from CWD-infected pigs could present a potential source of CWD infectivity in the animal and human food chains.
www.ars.usda.gov/research/publications/publication/?seqNo115=353091
www.ars.usda.gov/research/project/?accnNo=432011&fy=2017
www.ars.usda.gov/research/publications/publication/?seqNo115=337105
CONFIDENTIAL
EXPERIMENTAL PORCINE SPONGIFORM ENCEPHALOPATHY
LINE TO TAKE
3. If questions on pharmaceuticals are raised at the Press conference, the suggested line to take is as follows:-
"There are no medicinal products licensed for use on the market which make use of UK-derived porcine tissues with which any hypothetical “high risk" ‘might be associated. The results of the recent experimental work at the CSM will be carefully examined by the CSM‘s Working Group on spongiform encephalopathy at its next meeting.
DO Hagger RM 1533 MT Ext 3201
web.archive.org/web/20030822054419/www.bseinquiry.gov.uk/files/yb/1990/09/21009001.pdf
While this clearly is a cause for concern we should not jump to the conclusion that this means that pigs will necessarily be infected by bone and meat meal fed by the oral route as is the case with cattle. ...
web.archive.org/web/20031026000118/www.bseinquiry.gov.uk/files/yb/1990/08/23004001.pdf
we cannot rule out the possibility that unrecognised subclinical spongiform encephalopathy could be present in British pigs though there is no evidence for this: only with parenteral/implantable pharmaceuticals/devices is the theoretical risk to humans of sufficient concern to consider any action.
web.archive.org/web/20030822031154/www.bseinquiry.gov.uk/files/yb/1990/09/10007001.pdf
May I, at the outset, reiterate that we should avoid dissemination of papers relating to this experimental finding to prevent premature release of the information. ...
web.archive.org/web/20030822052332/www.bseinquiry.gov.uk/files/yb/1990/09/11005001.pdf
3. It is particularly important that this information is not passed outside the Department, until Ministers have decided how they wish it to be handled. ...
web.archive.org/web/20030822052438/www.bseinquiry.gov.uk/files/yb/1990/09/12002001.pdf
But it would be easier for us if pharmaceuticals/devices are not directly mentioned at all. ...
web.archive.org/web/20030518170213/www.bseinquiry.gov.uk/files/yb/1990/09/13004001.pdf
Our records show that while some use is made of porcine materials in medicinal products, the only products which would appear to be in a hypothetically ''higher risk'' area are the adrenocorticotrophic hormone for which the source material comes from outside the United Kingdom, namely America China Sweden France and Germany. The products are manufactured by Ferring and Armour. A further product, ''Zenoderm Corium implant'' manufactured by Ethicon, makes use of porcine skin - which is not considered to be a ''high risk'' tissue, but one of its uses is described in the data sheet as ''in dural replacement''. This product is sourced from the United Kingdom.....
web.archive.org/web/20030822054419/www.bseinquiry.gov.uk/files/yb/1990/09/21009001.pdf
Distribution CWD North America
www.usgs.gov/media/images/distribution-chronic-wasting-disease-north-america-0
Research Project: Elucidating the Pathobiology and Transmission of Transmissible Spongiform Encephalopathies Location: Virus and Prion Research
2023 Annual Report
snip...
Accomplishments
1. Sheep scrapie agent can infect white-tailed deer after oronasal exposure. The origin of chronic wasting disease (CWD) is not known, but it has many similarities to the prion disease of sheep called scrapie. It has long been hypothesized that CWD could have arisen through transmission of sheep scrapie to deer. ARS researches in Ames, Iowa, conducted a study to determine if scrapie derived from sheep could be transmitted to white-tailed deer. This study reports that the deer inoculated with sheep scrapie developed clinical signs of TSE and that the abnormal prion protein could be detected in a wide range of neural and lymphoid tissues. These results indicate that deer may be susceptible to sheep scrapie if exposed to the disease in natural or agricultural settings. In addition, several strong similarities between CWD in white-tailed deer and the experimental cases of scrapie in white-tailed deer in this report suggest that it would be difficult to identify scrapie in deer were a case to occur. This information should be considered when developing plans to reduce or eliminate TSEs or advising farmers that wish to keep their deer herds free from prion diseases.
2. A novel sampling method was developed for monitoring CWD in farmed cervids to help maintain a CWD free environment. While the transmissible spongiform encephalopathies (TSEs) scrapie and bovine spongiform encephalopathy (BSE) have been largely controlled through selective breeding and a ruminant feed ban respectively, neither approach is applicable to chronic wasting disease (CWD).
www.ars.usda.gov/research/project/?accnNo=440677&fy=2023
Terry S. Singeltary Sr.
State kills hundreds of deer at North Texas ranch, after years of legal fights
BY EMILY BRINDLEY UPDATED MAY 31, 2024 10:53 AM
In a November legal filing, the state wrote that RW Trophy Ranch “now hosts the worst-ever CWD outbreak in Texas.” In a mid-March filing, the department notified the state Supreme Court that there had been 208 positive CWD cases at the ranch over the previous three years. Parks and Wildlife staff said this week that the number continued to rise, and reached 254 by Tuesday morning.
www.star-telegram.com/news/state/texas/article288479815.html#storylink=cpy
Texas TAHC TPWD Confirm 132 More Cases of CWD TSE PrP
Jumps from 663 in March, to 795 Positive In May 2024, wow!
tpwd.texas.gov/huntwild/wild/diseases/cwd/positive-cases/listing-cwd-cases-texas.phtml#texasCWD
Listing of CWD Cases in Texas
Show entries
Positive Number CWD Positive Confirmation Date Free Range Captive County Source Species Sex Age
795 2024-05-16 White-tailed Deer Hunt Facility #9 White-tailed Deer - Breeder Deer F 2.9
794 2024-05-16 White-tailed Deer Hunt Facility #9 White-tailed Deer - Breeder Deer F 2.9
793 2024-05-16 White-tailed Deer Hunt Facility #9 White-tailed Deer - Breeder Deer F 2.9
792 2024-05-16 White-tailed Deer Hunt Facility #9 White-tailed Deer - Breeder Deer F 4.8
791 2024-05-16 White-tailed Deer Hunt Facility #9 White-tailed Deer - Breeder Deer F 6.8
790 2024-05-16 White-tailed Deer Hunt Facility #9 White-tailed Deer - Breeder Deer M 3.8
789 2024-05-16 White-tailed Deer Hunt Facility #9 White-tailed Deer - Breeder Deer M 1.8
788 2024-05-16 White-tailed Deer Hunt Facility #9 White-tailed Deer - Breeder Deer M 2.9
787 2024-05-01 White-tailed Deer Frio Facility #21 White-tailed Deer - Breeder Deer F 4.7
786 2024-05-01 White-tailed Deer Frio Facility #21 White-tailed Deer - Breeder Deer M 2.7
785 2024-05-01 White-tailed Deer Frio Facility #21 White-tailed Deer - Breeder Deer F 4.7
784 2024-05-01 White-tailed Deer Frio Facility #21 White-tailed Deer - Breeder Deer M 2.7
783 2024-05-01 White-tailed Deer Frio Facility #21 White-tailed Deer - Breeder Deer M 2.7
782 2024-05-01 White-tailed Deer Frio Facility #21 White-tailed Deer - Breeder Deer M 1.7
781 2024-05-01 White-tailed Deer Frio Facility #21 White-tailed Deer - Breeder Deer M 2.7
780 2024-05-01 White-tailed Deer Frio Facility #21 White-tailed Deer - Breeder Deer M 2.7
779 2024-05-01 White-tailed Deer Frio Facility #21 White-tailed Deer - Breeder Deer M 2.7
778 2024-05-01 White-tailed Deer Frio Facility #21 White-tailed Deer - Breeder Deer M 3.7
777 2024-05-01 White-tailed Deer Frio Facility #21 White-tailed Deer - Breeder Deer M 2.7
776 2024-05-01 White-tailed Deer Zavala Facility #17 White-tailed Deer - Breeder Deer F 8.8
775 2024-05-01 White-tailed Deer Zavala Facility #17 White-tailed Deer - Breeder Deer F 2.8
774 2024-05-01 White-tailed Deer Zavala Facility #17 White-tailed Deer - Breeder Deer F 2.8
773 2024-05-01 White-tailed Deer Zavala Facility #17 White-tailed Deer - Breeder Deer F 6.8
772 2024-05-01 White-tailed Deer Zavala Facility #17 White-tailed Deer - Breeder Deer F 14.8
Showing 1 to 24 of 795 entries
*CWD Positive Confirmation Dates marked with * are dates confirmed by Texas A&M Veterinary Diagnostic Laboratory rather than the National Veterinary Diagnostic Laboratory.
tpwd.texas.gov/huntwild/wild/diseases/cwd/positive-cases/listing-cwd-cases-texas.phtml#texasCWD
THURSDAY, MAY 30, 2024
Texas TAHC TPWD Confirm 132 More Cases of CWD TSE PrP 795 Positive To Date
chronic-wasting-disease.blogspot.com/2024/05/texas-tahc-tpwd-confirm-132-more-cases.html
THURSDAY, MARCH 07, 2024
Texas TPWD CWD Cases Jump to 663 Confirmed To Date
chronic-wasting-disease.blogspot.com/2024/03/texas-tpwd-cwd-cases-jump-to-663.html
those zombie looking deer, well that's a very misleading title to call chronic wasting disease cwd tse prion of cervid, because a perfectly healthy looking deer can have chronic wasting disease cwd tse prion, and be just as deadly.
why is this so stupid, oh, let me count the ways...terry
Diagnosis of preclinical CWD in farmed white-tailed deer in Canada by the immunohistochemical examination of recto-anal mucosa- associated lymphoid tissue (RAMALT)
''The apparent prevalence of disease in these two farms was 21% and 31%.''
“None of these deer were demonstrating signs consistent with CWD.”
www.ars.usda.gov/research/publications/publication/?seqNo115=244240
''The apparent prevalence of disease in these two farms was 21% and 31%.''
'This report summarizes the comparative diagnostic performance of postmortem rectoanal mucosa-associated lymphoid tissue (RAMALT) sampling in two white-tailed deer farms from Saskatchewan, Canada. The apparent prevalence of disease in these two farms was 21% and 31%.'' Title: Diagnosis of preclinical CWD in farmed white-tailed deer in Canada by the immunohistochemical examination of recto-anal mucosa- associated lymphoid tissue (RAMALT)
Author BALACHANDRAN, ARU - Canadian Food Inspection Agency THOMSEN, BRUCE - Animal And Plant Health Inspection Service (APHIS) GIDLEWSKI, THOMAS - Animal And Plant Health Inspection Service (APHIS) SPRAKER, TERRY - Colorado State University MITCHELL, G - Canadian Food Inspection Agency SOUTYRINE, ANDREI - Canadian Food Inspection Agency HARRINGTON, NOEL - Canadian Food Inspection Agency MUNGER, RANDY - Animal And Plant Health Inspection Service (APHIS) Schneider, David O'Rourke, Katherine
Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: 9/12/2009
Publication Date: 9/22/2009
Citation: Balachandran, A., Thomsen, B.V., Gidlewski, T., Spraker, T.R., Mitchell, G., Soutyrine, A., Harrington, N.P., Munger, R., Schneider, D.A., Orourke, K.I. 2009.
Diagnosis of preclinical CWD in farmed white-tailed deer in Canada by the immunohistochemical examination of recto-anal mucosa- associated lymphoid tissue (RAMALT).
NeuroPrion Workshop: New developments in TSEs of domestic and wild animals. pg.9
Interpretive Summary: Diagnosis of prion disease [for example, scrapie in sheep and chronic wasting disease (CWD) in elk and deer] relies upon sensitive detection of disease-associated prion protein in the brain or tissues containing lymph follicles. Live animal testing for scrapie disease in sheep has included evaluation of biopsy samples of the tonsil, third eyelid and rectal mucosa. Similarly, diagnosis of CWD in live elk has been recently accomplished through biopsy of the rectal mucosa. This invited report to the annual NeuroPrion meeting summarizes the diagnostic performance (test sensitivity) of various tissue sampling sites that were collected after death. The report summarizes the findings from two different populations of captive white-tailed deer from Saskatchewan, Canada. The diagnostic performance of the rectal mucosa samples were similar but lower than that achieved in two other lymphoid tissues, but greater than that achieved in the brain. While these studies were conducted on tissues collected after death, the findings demonstrate the comparative potential for biopsy of the rectal mucosa in live deer not yet showing signs of disease. While many factors may influence test performance in other deer populations, these studies showed that false-negative diagnosis occurred most often in deer presumed to be in an early stage of disease and carrying a mutation in the prion protein gene (codon 96).
Technical Abstract: This report summarizes the comparative diagnostic performance of postmortem rectoanal mucosa-associated lymphoid tissue (RAMALT) sampling in two white-tailed deer farms from Saskatchewan, Canada. The apparent prevalence of disease in these two farms was 21% and 31%. None of these deer were demonstrating signs consistent with CWD. The overall tissue-specific test sensitivities were ranked: RPLN>tonsil>RAMALT>obex. Test sensitivities in deer having at least one PRNP G96S allele were generally lower but similarly ranked. False negative RAMALT results were associated with early disease progression, as assessed by PrPCWD accumulation scores in the obex, and/or the PRNP G96S allele. The proportion of CWD-positive RAMALT follicles were generally lowest in deer early in disease progression and/or heterozygous at PRNP codon 96. And, as expected, variation in the proportion CWD-positive RAMALT follicles was inversely related to the total number of observable follicles per sample. These comparisons made on samples collected postmortem suggest general diagnostic evaluation of RAMALT samples in white-tailed deer would have intermediate test sensitivity as compared to evaluation of RPLN and obex. While many factors may influence actual test performance, early stage of disease progression and the PRNP G96S allele are two that were associated with lower test sensitivities.
www.ars.usda.gov/research/publications/publication/?seqNo115=244240
Texas Kimble County Farm Chronic Wasting Disease CWD TSE Prion Approximate Herd Prevalence 12%
SUMMARY MINUTES OF THE 407th COMMISSION MEETING Texas Animal Health Commission
September 22, 2020
Chronic Wasting Disease (CWD):
A new CWD positive breeding herd was disclosed in February 2020 in Kimble County. This herd depopulation was completed in July 2020. Including the two index positive deer, an additional eight more positive deer were disclosed (approximate herd prevalence 12%). Since July 2015 and prior to this discovery, five positive captive breeder herds have been disclosed and four of those are in Medina County. One herd in Lavaca and three herds in Medina County were depopulated leaving one large herd in Medina County that is managed on a herd plan. A new zone was established in Val Verde County in December 2019 as a result of a positive free-ranging White-tailed Deer (WTD). A second positive WTD was also disclosed in February 2020 in the same area.
SUMMARY MINUTES OF THE 407th COMMISSION MEETING – 9/22/2020
Scrapie: The flock identified in April 2016 remains under quarantine in Hartley County.
www.tahc.texas.gov/agency/meetings/minutes/SummaryMinutes_CommMtg_2020-09-22
web.archive.org/web/20201017124040/https://www.tahc.texas.gov/agency/meetings/minutes/SummaryMinutes_CommMtg_2020-09-22.pdf
TEST RESULTS FROM CAPTIVE DEER HERD WITH CHRONIC WASTING DISEASE RELEASED 79.8 percent of the deer tested positive for the disease
DES MOINES – The Iowa Department of Agriculture and Land Stewardship today announced that the test results from the depopulation of a quarantined captive deer herd in north-central Iowa showed that 284 of the 356 deer, or 79.8% of the herd, tested positive for Chronic Wasting Disease (CWD).
web.archive.org/web/20141006172620/http://www.iowaagriculture.gov/press/2014press/press10022014.asp
web.archive.org/web/20140917023729/http://www.iowadnr.gov/Portals/idnr/uploads/Hunting/060613_consent_order.pdf
Wisconsin Buckhorn Flats CWD
SUBJECT: Almond Deer Farm Update
The first case of Chronic Wasting Disease (CWD) among Wisconsin's farm-raised deer occurred in a white-tailed deer buck shot by a hunter at the property (formerly known as Buckhorn Flats) in September 2002. This situation prompted the eventual depopulation of the entire farm.
The deer, a mix of does and yearlings, were destroyed on January 17, 2006- 4 years later- by U.S. Department of Agriculture shooters under a USDA agreement with the farm owner.
Sixty of the 76 animals tested positive for CWD. The 76 deer constituted the breeding herd in the breeding facility on the farm. The property also had a hunting preserve until 2005. Four deer, two does and two fawns, the only deer remaining in the former preserve, were killed and tested as well. CWD was not detected in those animals.
The total number of deer to test positive from this farm from the initial discovery to final depopulation is 82. The nearly 80% prevalence rate discovered on Buckhorn Flats is the highest prevalence recorded in any captive cervid operation in North America.
Tuesday, December 20, 2011
Chronic Wasting Disease CWD WISCONSIN Almond Deer
(Buckhorn Flats) Farm Update DECEMBER 2011 The CWD infection rate was nearly 80%, the highest ever in a North American captive herd. RECOMMENDATION: That the Board approves the purchase of 80 acres of land for $465,000 for the Statewide Wildlife Habitat Program in Portage County and approve the restrictions on public use of the site.
Form 1100-001 (R 2/11) NATURAL RESOURCES BOARD AGENDA ITEM SUBJECT: Information Item: Almond Deer Farm Update FOR:
DECEMBER 2011 BOARD MEETING
TUESDAY TO BE PRESENTED BY TITLE: Tami Ryan, Wildlife Health Section Chief SUMMARY:
dnr.wi.gov/about/nrb/2011/december/12-11-2b2.pdf
web.archive.org/web/20141015022916/http://dnr.wi.gov/about/nrb/2011/december/12-11-2b2.pdf
September 1, 2008
Chronic Wasting Disease in a Wisconsin White-Tailed Deer Farm
Delwyn P. Keane Delwyn.Keane@wvdl.wisc.edu, Daniel J. Barr, […], and Michael D. Samuel+5 View all authors and affiliations Volume 20, Issue 5
doi.org/10.1177/104063870802000534
In September 2002, chronic wasting disease (CWD), a prion disorder of captive and wild cervids, was diagnosed in a white-tailed deer (Odocoileus virginianus) from a captive farm in Wisconsin. The facility was subsequently quarantined, and in January 2006 the remaining 76 deer were depopulated. Sixty animals (79%) were found to be positive by immunohistochemical staining for the abnormal prion protein (PrPCWD)in at least one tissue; the prevalence of positive staining was high even in young deer. Although none of the deer displayed clinical signs suggestive of CWD at depopulation, 49 deer had considerable accumulation of the abnormal prion in the medulla at the level of the obex. Extraneural accumulation of the abnormal protein was observed in 59 deer, with accumulation in the retropharyngeal lymph node in 58of 59 (98%), in the tonsil in 56 of 59 (95%), and in the rectal mucosal lymphoid tissue in 48 of 58 (83%). The retina was positive in 4 deer, all with marked accumulation of prion in the obex. One deer was considered positive for PrPCWD in the brain but not in the extraneural tissue, a novel observation in white-tailed deer. The infection rate in captive deer was 20-fold higher than in wild deer. Although weakly related to infection rates in extraneural tissues, prion genotype was strongly linked to progression of prion accumulation in the obex. Antemortem testing by biopsy of rectoanal mucosal-associated lymphoid tissue (or other peripheral lymphoid tissue) may be a useful adjunct to tonsil biopsy for surveillance in captive herds at risk for CWD infection.
''The facility was subsequently quarantined, and in January 2006 the remaining 76 deer were depopulated. Sixty animals (79%) were found to be positive by immunohistochemical staining for the abnormal prion protein (PrPCWD)in at least one tissue; the prevalence of positive staining was high even in young deer.''
journals.sagepub.com/doi/10.1177/104063870802000534
The infection rates among some captive deer can be much higher, with a rate of 79% (nearly 4 in 5) reported from at least one captive herd.
www.cdc.gov/prions/cwd/occurrence.html
CWD Deer Herd Population Declines
CWD poses a significant threat to the future of hunting in Texas. Deer population declines of 45 and 50 percent have been documented in Colorado and Wyoming. A broad infection of Texas deer populations resulting in similar population impacts would inflict severe economic damage to rural communities and could negatively impact land markets. Specifically, those landowners seeking to establish a thriving herd of deer could avoid buying in areas with confirmed CWD infections. As they do with anthrax-susceptible properties, land brokers may find it advisable to inquire about the status of CWD infections on properties that they present for sale. Prospective buyers should also investigate the status of the wildlife on prospective properties. In addition, existing landowners should monitor developments as TPWD crafts management strategies to identify and contain this deadly disease.
Dr. Gilliland (c-gilliland@tamu.edu) is a research economist with the Texas Real Estate Research Center at Texas A&M University.
www.recenter.tamu.edu/articles/tierra-grande/oh-deer-2314
Colorado CWD TSE Prion Detected in 40 of 54 deer herds, 17 of 42 elk herds, and 2 of 9 moose herds
cpw.state.co.us/Documents/Commission/2022/May/Item.11-PWC_Memo_CWD_Update_EckertMillerWood_April2022-Matthew_Eckert-DNR.pdf
Colorado CWD figures just out; COLORADO CWD UPDATE
Notably, prevalence in the White River herd, one of the state’s largest, rose from 15.3% to 23.6%.
Prevalence increased by about 10%, to 14%, in the Uncompahgre herd, and grew from 3.5% to 8% in the Middle Park herd.
Prevalence fell from 13.6% to 6.7% in the Sweetwater herd and from 12% to 8% in the Big Thompson herd.
Parks and Wildlife has detected the disease in 40 of Colorado’s 54 deer herds, 17 of its 42 elk herds and two of its nine moose herds.
www.gjsentinel.com/news/western_colorado/chronic-wasting-disease-battle-continues/article_3f3e09e2-321a-11ee-a836-bb106b337e90.html
Colorado Chronic Wasting Disease Response Plan December 2018.
Executive Summary Mule deer, white-tailed deer, elk and moose are highly valued species in North America. Some of Colorado’s herds of these species are increasingly becoming infected with chronic wasting disease(CWD).
As of July 2018, at least 31 of Colorado's 54 deer herds (57%), 16 of43 elk herds (37%), and 2 of 9 moose herds (22%) are known to be infected with CWD.
Four of Colorado's 5 largest deer herds and 2 of the state’s 5 largest elk herds are infected.
Deer herds tend to be more heavily infected than elk and moose herds living in the same geographic area.
Not only are the number of infected herds increasing, the past 15 years of disease trends generally show an increase in the proportion of infected animals within herds as well.
Of most concern, greater than a 10-fold increase in CWD prevalence has been estimated in some mule deer herds since the early 2000s; CWD is now adversely affecting the performance of these herds.
snip...(the map on page 71, cwd marked in red, is shocking...tss)
cpw.state.co.us/Documents/RulesRegs/Brochure/BigGame/biggame.pdf
cpw.state.co.us/Documents/Hunting/BigGame/CWD/PDF/ColoradoChronicWastingDiseaseResponsePlan.pdf
Since identifying its first cases of CWD in captive deer in the 70s and finding the first wild infected deer in 1985, Wyoming has seen the disease slowly spread throughout the state. CWD has now been documented in members of the deer family in most of Wyoming’s deer hunting areas, with 20% to 40% percent of mule deer affected in some herds. A 2017 study estimated a 21% annual population decline as a result of the fatal disease.
freerangeamerican.us/chronic-wasting-disease-wyoming/#:~:text=CWD%20has%20now%20been%20documented,result%20of%20the%20fatal%20disease.
How does CWD impact deer, elk, and moose populations?
Recent research in Wyoming has demonstrated declines in both mule and white-tailed deer populations in deer hunt area 65 due to CWD (see below for citations). These declines are in the core endemic area where prevalence is highest. In areas with lower prevalence, effects of CWD are poorly understood but are considered additive along with other factors that can negatively affect deer populations in Wyoming (i.e. habitat loss, predation, other diseases). The distribution and prevalence of CWD in Wyoming elk is less than that of deer. Currently there are no documented direct population impacts in Wyoming elk from CWD; however, research from Rocky Mountain National Park suggests that CWD could impact elk populations at higher prevalence (13%). While CWD has been found in free ranging moose, there have been few detections, and there is no evidence that CWD is currently having an impact on moose populations.
wgfd.wyo.gov/Wildlife-in-Wyoming/More-Wildlife/Wildlife-Disease/Chronic-Wasting-Disease
WYOMING, POWELL — Sobering news resulting from a multi-year Chronic Wasting Disease (CWD) surveillance program by the Wyoming Game and Fish Department between 2018 and 2022 shows significant increases in the fatal disease for the state’s prized mule deer and elk herds.
In one herd, the prevalence rate is calculated at 65% in mule deer bucks, and there are concerning increases in infected elk, including hunt areas popular for Big Horn Basin hunters.
The disease, which typically kills infected animals within two years after initial exposure, now occurs in 34 of Wyoming’s 37 mule deer herds, and 15 of the state’s 36 elk herd units.
www.wyomingnews.com/rocketminer/news/state/cwd-increasing-in-state-deer-elk-herds/article_1005894a-361e-11ee-8900-0743386c0b87.html
Texas CWD Surveillance Positives (cwd totals confirmed at 663 is outdated)
tpwd.texas.gov/huntwild/wild/diseases/cwd/positive-cases/listing-cwd-cases-texas.phtml#texasCWD
Counties where CWD Exposed Deer were Released
tpwd.texas.gov/documents/257/CWD-Trace-OutReleaseSites.pdf
Number of CWD Exposed Deer Released by County
tpwd.texas.gov/documents/258/CWD-Trace-OutReleaseSites-NbrDeer.pdf
Chronic Wasting Disease CWD Captive Herds updated April 2023
www.aphis.usda.gov/aphis/ourfocus/animalhealth/animal-disease-information/cervid/cervids-cwd/cervids-voluntary-hcp
Chronic Wasting Disease CWD Captive Herds updated April 2023
www.aphis.usda.gov/animal_health/animal_diseases/cwd/downloads/status-of-captive-herds.pdf
TPWD Proposed Amendments to Chronic Wasting Disease and canned hunting Mountain lions ban
Proposed Regulations
Learn more and comment online through 5 p.m. May 22, 2024.
As noted previously in this preamble, the department has been engaged in a long-term effort to stem the spread of CWD; however, by 2021 it was apparent that more robust measures were warranted because CWD was still being detected in additional deer breeding facilities, as well as on multiple release sites associated with CWD-positive deer breeding facilities. The commission adopted those rules, which require higher rates of testing, ante-mortem (live-animal) testing of breeder deer prior to release, and enhanced recordkeeping and reporting measures, in December of 2021 (46 TexReg 8724).
Following the implementation of more efficacious testing requirements, an unprecedented increase in CWD detections occurred. Since 2021, CWD has been detected in 22 deer breeding facilities, two release sites associated with CWD-positive deer breeding facilities, and two free-ranging deer in areas where CWD had not been previously detected. Department records indicate that within the last five years those breeding facilities transferred over 7,000 deer to other breeding facilities, release sites, and Deer Management Permit (DMP) sites. All those locations are therefore directly connected to the CWD-positive facilities and are subsequently of epidemiological concern. Additionally, approximately 287 deer breeding facilities received deer from one or more of the directly connected breeding facilities, which means those facilities (referred to as “Tier 1” facilities) are indirectly connected to the positive facilities and are also of epidemiological concern because they have received exposed deer that were in a trace-out breeding facility.
Because of this rapid explosion in epidemiological linkages between deer breeding facilities and associated release sites, the department became concerned about the excessive numbers of deer breeders continuing to be affected by inter-facility transfers, and subsequently determined that additional testing measures could increase the probability of detecting CWD in breeding facilities where it exists before it could be spread to additional breeding facilities and associated release sites.
Learn more and comment online through 5 p.m. May 22, 2024.
tpwd.texas.gov/business/feedback/public_comment/proposals/202405_cwd_rules.phtml
TEXAS BREEDER DEER ESCAPEE WITH CWD IN THE WILD, or so the genetics would show?
OH NO, please tell me i heard this wrong, a potential Texas captive escapee with cwd in the wild, in an area with positive captive cwd herd?
apparently, no ID though. tell me it ain't so please...
23:00 minute mark
''Free Ranging Deer, Dr. Deyoung looked at Genetics of this free ranging deer and what he found was, that the genetics on this deer were more similar to captive deer, than the free ranging population, but he did not see a significant connection to any one captive facility that he analyzed, so we believe, Ahhhhhh, this animal had some captive ahhh, whatnot.''
youtu.be/aoPDeGL6mpQ?t=1384
Commission Agenda Item No. 5 Exhibit B
DISEASE DETECTION AND RESPONSE RULES
PROPOSAL PREAMBLE
1. Introduction.
snip...
A third issue is the accuracy of mortality reporting. Department records indicate that for each of the last five years an average of 26 deer breeders have reported a shared total of 159 escapes. Department records for the same time period indicate an average of 31 breeding facilities reported a shared total of 825 missing deer (deer that department records indicate should be present in the facility, but cannot be located or verified).
tpwd.texas.gov/business/feedback/meetings/2022/1104/agenda/item.phtml?item=5
On January 21, 2017 a tornado took down thousands of feet of fence for a 420-acre illegal deer enclosure in Lamar County that had been subject to federal and state investigation for illegally importing white-tailed deer into Mississippi from Texas (a CWD positive state). Native deer were free to move on and off the property before all of the deer were able to be tested for CWD. Testing will be made available for a period of three years for CWD on the property and will be available for deer killed within a 5-mile radius of the property on a voluntary basis.
www.mdwfp.com/media/254796/2016-17-deer-report.pdf
“It is interesting to note that, in 2001, the State of Texas shifted its deer management strategies toward the same leanings that Kroll has suggested for Wisconsin. In Texas, the change was brought about via heavy lobbying from the high-fence deer ranching industry. This pressure helped convince the Texas Parks and Wildlife to change their regulations and allow private landowners to select the own deer biologists.”
www.texasmonthly.com/story/which-side-fence-are-you
Chronic Wasting Disease in Texas
A Real Disease with Proven Impacts
Produced by a coalition of concerned hunters, landowners, & conservationists (last update 08/2023)
Snip…
Since 2012, CWD has been detected in wild deer in just 7 counties in Texas and is only established in the western panhandle and far west Texas.
In that same period of time, captive deer breeders have exposed almost half of Texas counties to CWD.
Deer held in captive breeding facilities are confined to much tighter spaces, and have intimate contact with many more animals on a daily basis. By far the greatest factor in amplifying the spread of CWD is the artificial movement of these animals, shipped in livestock trailers hundreds of miles, far outside of their natural home range, and ultimately released to co-mingle with wild deer.
Each year, Texas captive deer breeders liberate 20,000-30,000 deer from their pens to the wild.
For every deer breeding facility where a CWD positive deer is discovered, an epidemiological investigation is conducted by the Texas Parks & Wildlife Department and the Texas Animal Health Commission to determine how many other deer may have been exposed to the disease and where they have been shipped. Because of the prolific artificial movement of captive deer, one deer with CWD can impact hundreds of other facilities and ranches across the state.
Unfortunately, released deer in Texas are not required to retain any kind of visible identification (an ear tag), and for this reason, the vast majority of released deer cannot be relocated for testing.
As of August 2023, 116 Texas counties have received possibly infected breeder deer that cannot be located, putting more than 140,000 landowners at risk of the disease.
Snip
The state of Texas has been testing for CWD since 2002. Since that time, more than 302,360 captive and free range deer have been tested.
From 2015-2022, more than 127,000 samples were collected from hunter-harvested and roadkill deer. This sampling rate and risk-based distribution provides scientists confidence that they would have detected the disease if it existed at a very low prevalence (<1%) in any given region at the time sampling began.
Snip…
We have learned from other states where CWD has been present the longest, that a constant increase in the prevalence of the disease may lead to a significant decline in the deer population. When disease prevalence exceeds 20%, deer populations have declined by up to 50%. In some areas of Colorado, where CWD has been present since 1985, mule deer abundance has declined by 45% since that time, despite adequate habitat and no hunting ( Miller et al. 2008 ). Similarly, the South Converse Game Unit in Wyoming has documented CWD prevalence exceeding 50% and has seen an approximate 50% decline in mule deer populations.
Snip…
Rural Economies
Deer hunting is the lifeblood of rural Texas. White-tailed deer hunting is by far the most impactful segment of the hunting economy, representing $4.3 billion, according to a recent Texas A&M Study. And while deer breeders represent a very small segment of that economy (less than 5%), they represent one of the greatest risks. ( Full Texas A&M Report )
Real Estate
Rural land prices are largely driven by recreational buyers with hunting as a top land amenity. Without deer hunting, many of these properties will be worth much less.
Conservation Funding
Deer hunters are the largest funders of wildlife conservation in Texas through excise taxes on firearms, ammunition, and gear along with active membership supporting and funding conservation organizations. If deer hunting suffers due to CWD, all wildlife in Texas lose.
Culture & Health
Texas’ native deer herd has iconic value for all Texans. Deer hunting brings families together, creates camaraderie in communities, and serves to connect Texans to nature. There is no better protein than wild, locally harvested, non-GMO and totally organic venison. A healthy deer herd leads to healthy Texans and a healthy and prosperous Texas.
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This isn't a disease for our lifetime. It's a disease for our grandchildren's lifetime.
- Dr. Bob Dittmar, Former Texas State Wildlife Veterinarian
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See the full text with maps, graphs, much more, excellent data…
bit.ly/3xL16Gm
Since 2012, CWD has been detected in wild deer in just 7 counties in Texas and is only established in the western panhandle and far west Texas.
In that same period of time, captive deer breeders have exposed almost half of Texas counties to CWD.
bit.ly/3xL16Gm
As of August 2023, 116 Texas counties have received possibly infected breeder deer that cannot be located, putting more than 140,000 landowners at risk of the disease.
bit.ly/3xL16Gm
ECONOMIC VALUES OF WHITE-TAILED DEER IN TEXAS
2022 SURVEY: PART I
web.archive.org/web/20230809171452/https://nri.tamu.edu/media/3702/economic-values-of-white-tailed-deer-in-texas-2022-survey-part-i.pdf
Don't mess Texas, or with Mother Nature in Texas, but, seems things went terribly wrong down here in Texas with CWD, be careful what you ask for;
TEXAS CWD STRAIN
“Wow,” he said. “Unlike anything we've seen before.”
The disease devastating deer herds may also threaten human health
Scientists are exploring the origins of chronic wasting disease before it becomes truly catastrophic.
Rae Ellen Bichell
Image credit: David Parsons/Istock
April 8, 2019
This story was published in collaboration with the Mountain West News Bureau, a collaboration between Wyoming Public Media, Boise State Public Radio in Idaho, KUER in Salt Lake City and KRCC and KUNC in Colorado.
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One day in late February, in their laboratory in Fort Collins, Colorado, Wagner and Zabel compared the prions from the brains of CWD-infected deer in Texas with those of elk in Colorado. They want to know if the proteins were all mangled in the same way, or not. “If they are different, this would suggest that we have different strain properties, which is evidence as we're building our case that we might have multiple strains of CWD circulating in the U.S.,” says Wagner.
Step one is to see if they’re equally easy to destroy using a chemical called guanidine. The shape of a prion dictates everything, including the way it interacts with an animal’s cells and the ease with which chemicals can unfold it.
“Moment of truth,” said Wagner, as she and Zabel huddled around a computer, waiting for results to come through. When they did, Zabel was surprised.
“Wow,” he said. “Unlike anything we've seen before.”
The prions from the Texas deer were a lot harder to destroy than the ones from the Colorado elk. In fact, the guanidine barely damaged them at all. “We’ve never seen that before in any prion strain, which means that it has a completely different structure than we've ever seen before,” says Zabel. And that suggests that it might be a very different kind of chronic wasting disease. The researchers ran the same test on another Texas deer, with the same results.
Now, these are only the preliminary results from a few animals. Wagner and Zabel have a lot more experiments to do. But if future tests come to the same conclusion, it would support their hypothesis that there are multiple strains of chronic wasting disease out there, all with different origins. That, in turn, could mean that this disease will become even trickier to manage than it already is.
And, Zabel adds, there’s something else. “If it's still evolving, it may still evolve into a form that could potentially, eventually affect humans,” he says.
Zabel is not the only one worried about that possibility.
OSTERHOLM, THE EPIDEMIOLOGIST from Minnesota, is also concerned. He directs the Center for Infectious Disease Research and Policy at the University of Minnesota, and is serving a one-year stint as a “Science Envoy for Health Security” with the U.S. State Department. In February, he told Minnesota lawmakers that when it comes to chronic wasting disease, we are playing with fire. “You are going to hear from people that this is not going to be a problem other than a game farm issue. You're going to hear from people that it's not going to transmit to people, and I hope they're right, but I wouldn't bet on it,” he said. “And if we lose this one and haven’t done all we can do, we will pay a price.”
If that wasn’t warning enough, he added: “Just remember what happened in England.”
He was talking about mad cow disease. Decades ago, Osterholm got involved in studying the potential for the newly emerging condition — bovine spongiform encephalopathy, or BSE for short — to be transmitted to humans.
At that point, researchers had yet to document a prion disease in animals that could infect people. They did, however, have a few pieces of the puzzle. For one, work in Papua New Guinea had shown that people could transmit prion diseases to each other if they practiced cannibalism, especially of the brain-eating variety. They also knew that BSE was spreading quickly between cattle. Osterholm says he and others worried that the more widespread it became, the more chances it might have to change into something that could sicken people.
“A lot of people thought that it was an overreaction,” says Osterholm. “Then, of course, in 1996, 10 years later, we recognized that in fact transmission had occurred.” Variant Creutzfeldt-Jakob disease, as the illness is called when it appears in human beings, has infected about 230 people worldwide. Osterholm says he feels like he’s having déjà vu, except that instead of mad cow, now it’s chronic wasting disease that’s spreading in animals, with the potential to cross the species barrier to infect humans.
SNIP...SEE FULL TEXT;
www.hcn.org/articles/wildlife-the-disease-devastating-deer-herds-may-also-threaten-human-health-science
TEXAS CWD STRAIN
77. Assessing chronic wasting disease strain differences in free-ranging cervids across the United States
Kaitlyn M. Wagnera, Caitlin Ott-Connb, Kelly Strakab, Bob Dittmarc, Jasmine Battend, Robyn Piercea, Mercedes Hennessya, Elizabeth Gordona, Brett Israela, Jenn Ballarde and Mark D Zabela
aPrion Research Center at Colorado State University; bMichigan Department of Natural Resources; cTexas Parks and Wildlife Department; dMissouri Department of Conservation, 5. Arkansas Game and Fish Commission CONTACT Kaitlyn M. Wagner miedkait@rams.colostate.edu
ABSTRACT
Background/Introduction: Chronic wasting disease (CWD) is an invariably fatal prion disease affecting captive and free-ranging cervids, including white-tailed deer, mule deer, moose, elk, and reindeer. Since the initial description of the disease in the 1960’s, CWD has spread to 23 states, 3 Canadian Provinces, South Korea, Norway and, most recently, Finland. While some outbreaks of CWD were caused by transport of infected animals from endemic regions, the origin of CWD in other epizootics is unclear and has not been characterized. Previous studies have shown that there are two distinct strains of CWD. However, the continuous spread and the unclear origin of several outbreaks warrant continued surveillance and further characterization of strain diversity.
Materials and Methods: To address these knowledge gaps, we used biochemical tests to assess strain differences between CWD outbreaks in Michigan, Texas, Missouri, and Colorado, USA. Brain or lymph node samples were homogenized and digested in 50 µg/mL proteinase K (PK). These samples were then run on a Western blot to assess glycoform ratio and electrophoretic mobility. Texas samples were digested in 100 µg/mL PK. To assess conformational stability, brain or lymph node homogenates were incubated in increasing concentrations of guanidine hydrochloride from 0 M to 4 M in 0.5 M increments. Samples were then precipitated in methanol overnight, washed and PK digested in 50 µg/mL PK before slot blotting.
Results: Our results have found significant differences in glycoform ratio between CWD from Michigan and Colorado, but no differences were observed in conformational stability assays. Interestingly, when testing our CWD isolates from Texas to analyse electrophoretic mobility and glycoform ratio, we found that these samples did not exhibit the characteristic band shift when treated with PK, but PK resistant material remained. Additionally, results from our conformational stability assay demonstrate a unique profile of these Texas isolates. Testing of samples from Missouri is currently underway.
Conclusions: Thus far, our data indicate that there are strain differences between CWD circulating in Michigan and CWD in Colorado and provide important insight into CWD strain differences between two non-contiguous outbreaks. We have also identified a unique strain of CWD in Texas with biochemical strain properties not seen in any of our other CWD isolates. These results highlight the importance of continued surveillance to better understand this devastating disease. These results have important implications for CWD emergence, evolution and our understanding of prion strain heterogeneity on the landscape.
www.tandfonline.com/doi/full/10.1080/19336896.2019.1615197
Breeding CWD from Cervid?
''However, to date, there are no reports of polymorphic cervid PrP alleles providing absolute resistance to CWD. Studies on polymorphisms have focused on those found in CWD-endemic areas, with the hope that understanding the role of an animal's genetics in CWD can help to predict, contain, or prevent transmission of CWD.''
pubmed.ncbi.nlm.nih.gov/33668798/
The presence of aa96S has been associated with slowed disease progression, longer life span among captive deer,Citation26,27 and does not appear to affect the rate at which prions are shed from infected individuals.Citation38 Additionally, CWD infected mule deer have been found to excrete pathogenic prions while asymptomatic.Citation39 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.
www.tandfonline.com/doi/full/10.1080/19336896.2015.1115179
***> at present, no PrPC allele conferring absolute resistance in cervids has been identified.
J Gen Virol. 2017 Nov; 98(11): 2882–2892.
Published online 2017 Oct 23. doi: 10.1099/jgv.0.000952
Estimating chronic wasting disease susceptibility in cervids using real-time quaking-induced conversion
Chronic wasting disease (CWD) resistance in cervids is often characterized as decreased prevalence and/or protracted disease progression in individuals with specific alleles; at present, no PrPC allele conferring absolute resistance in cervids has been identified.
www.ncbi.nlm.nih.gov/pmc/articles/PMC5845664/pdf/jgv-98-2882.pdf
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
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
web.archive.org/web/20161024005615/http://prion2016.org/dl/newsletter_03.pdf
chronic-wasting-disease.blogspot.com/2017/04/
''There are no known familial or genetic TSEs of animals, although polymorphisms in the PRNP gene of some species (sheep for example) may influence the length of the incubation period and occurrence of disease.''
c) The commonest form of CJD occurs as a sporadic disease, the cause of which is unknown, although genetic factors (particularly the codon 129 polymorphism in the prion protein gene (PRNP)) influence disease susceptibility. The familial forms of human TSEs (see Box 1) appear to have a solely genetic origin and are closely associated with mutations or insertions in the PRNP gene. Most, but not all, of the familial forms of human TSEs have been transmitted experimentally to animals. There are no known familial or genetic TSEs of animals, although polymorphisms in the PRNP gene of some species (sheep for example) may influence the length of the incubation period and occurrence of disease.
assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/209755/Part_1_-_Introduction.pdf
Examining PRNP gene frequencies and ‘resistance’ to chronic wasting disease
ACTIVE
By National Wildlife Health Center July 12, 2023
Overview Science
Multiple studies have demonstrated that various alleles of the cervid prion protein (PRNP) gene affect chronic wasting disease (CWD) progression.
Why this matters: Specific genetic differences in the cervid prion protein gene have been linked to disease ‘resistance’ and there is some evidence that gene frequencies in wild populations with high CWD prevalence are shifting towards these ‘resistant’ genotypes. It has been argued that this shift may eventually control CWD in the wild. A thorough examination of published science, however, suggests the situation may be more complex.
White-tailed deer in snow with forest in background and dried grass in foreground.
In white-tailed deer (Odocoileus virginianus), a putative ‘resistance’ allele encodes serine at amino acid 96 (96S) of the prion protein instead of the more common glycine (96G). Similarly, in mule deer (O. hemionus), a putative ‘resistance’ allele encodes phenylalanine at amino acid 225 (225F) instead of serine (225S). CWD has been found at lower abundance in heterozygous white-tailed deer with the 96S allele (96GS) and heterozygous mule deer with the 225F allele (225SF); CWD in homozygous 96S or 225F deer is rare (Johnson et al. 2006, Jewell et al. 2005). In experimental challenge studies all deer with 96S or 225F alleles (heterozygous or homozygous) contract CWD (Johnson et al. 2011, Wolfe et al. 2014, Plummer et al. 2017), but the presence of 96S or 225F, respectively, extends the incubation period. Although a prolonged incubation period may allow additional time for CWD+ deer to reproduce, it also increases opportunities for disease transmission and may allow disease prevalence to rise to a new equilibrium within endemic regions.
To increase our understanding of the potential impacts of disease-modifying alleles on CWD, the USGS National Wildlife Health Center and the Wisconsin Department of Natural Resources are examining PRNP gene frequencies in white-tailed deer to assess whether the relative abundance of Wisconsin deer expressing 96S has changed since the beginning of the epizootic. However, even if populations are shifting to higher frequencies of 96S or 225F, the resulting CWD epizootic trajectory may not be improved. Genetic resistance that can prevent infection by specific strains of pathogens must be distinguished from resistance that can prevent infection by all strains of that pathogen. In the context of CWD, the disease-modifying properties of 96S or 225F must be evaluated within a broader paradigm not only of the strains of CWD in circulation today, but also those that could arise in the future. For example, white-tailed deer with histidine at PRNP allele 95 give rise to a new emergent strain of CWD (termed H95+) when they are infected with the “wild-type” strain of CWD currently spreading in white-tailed deer. This H95+ CWD strain is likely to have very high attack rates in 96S deer (Duque Velasquez et al. 2015, Duque Velasquez et al. 2020). Similarly, serial passage of CWD in 225F mule-deer could stabilize a new strain adapted to 225F mule deer. Emergent strains of CWD prions may also have expanded host ranges and enhanced zoonotic potential (Herbst et al. 2017).
If the putative ‘resistance’ to CWD can be demonstrated, it should likely be considered temporary. As was observed with COVID-19, the evolutionary pattern of host resistance followed by pathogen adaptation is typical for infectious diseases and there are no known reasons to except CWD from this paradigm. The only known genetic modification that can induce general resistance to all prion strains are mutations that ablate expression of the mammalian prion protein. The resistance of cervids or other mammals to prion disease is a continuum of vulnerability that reflects both the host’s prion protein sequence and the specific prion strain that it is exposed to.
www.usgs.gov/centers/nwhc/science/examining-prnp-gene-frequencies-and-resistance-chronic-wasting-disease
“If slower disease progression results in longer-lived, infected deer with longer periods of infectiousness, resistance may lead to increased disease transmission rates, higher prion concentrations in the environment, and increased prevalence, as has been observed in some captive deer herds (Miller et al., 2006; Keane et al., 2008a).”
Genetic susceptibility to chronic wasting disease in free-ranging white-tailed deer: Complement component C1q and Prnp polymorphisms
Julie A. Blanchong a, *, Dennis M. Heisey b , Kim T. Scribner c , Scot V. Libants d , Chad Johnson e , Judd M. Aiken e , Julia A. Langenberg f , Michael D. Samuel g
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Identifying the genetic basis for heterogeneity in disease susceptibility or progression can improve our understanding of individual variation in disease susceptibility in both free-ranging and captive populations. What this individual variation in disease susceptibility means for the trajectory of disease in a population, however, is not straightforward. For example, the greater, but not complete, resistance to CWD in deer with at least one Serine (S) at amino acid 96 of the Prnp gene appears to be associated with slower progression of disease (e.g., Johnson et al., 2006; Keane et al., 2008a). If slower disease progression results in longer-lived, infected deer with longer periods of infectiousness, resistance may lead to increased disease transmission rates, higher prion concentrations in the environment, and increased prevalence, as has been observed in some captive deer herds (Miller et al., 2006; Keane et al., 2008a). Alternatively, if the slower progression of disease in resistant deer is not associated with longer periods of infectiousness, but might instead indicate a higher dose of PrPCWD is required for infection, transmission rates in the population could decline especially if, as in Wisconsin, deer suffer high rates of mortality from other sources (e.g., hunting). Clearly, determining the relationship between genetic susceptibility to infection, dose requirements, disease progression, and the period of PrPCWD infectiousness are key components for understanding the consequences of CWD to free-ranging populations.
pubmed.ncbi.nlm.nih.gov/19723593/#:~:text=After%20controlling%20for%20Prnp%2C%20we,strongly%20associated%20with%20CWD%20susceptibility.
web.archive.org/web/20121114223603/http://forest.wisc.edu/files/pdfs/samuel/2009%20blanchong%20et%20al%20genetic%20susceptibility%20chronic%20wasting.pdf
The presence of aa96S has been associated with slowed disease progression, longer life span among captive deer,Citation26,27 and does not appear to affect the rate at which prions are shed from infected individuals.Citation38 Additionally, CWD infected mule deer have been found to excrete pathogenic prions while asymptomatic.Citation39 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.Citation40 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).Citation26,30
www.tandfonline.com/doi/full/10.1080/19336896.2015.1115179
www.ncbi.nlm.nih.gov/pmc/articles/PMC4964855/pdf/kprn-09-06-1115179.pdf
Published: 07 October 2021
Review on PRNP genetics and susceptibility to chronic wasting disease of Cervidae
To date, chronic wasting disease (CWD) is the most infectious form of prion disease affecting several captive, free ranging and wild cervid species. Responsible for marked population declines in North America, its geographical spread is now becoming a major concern in Europe. Polymorphisms in the prion protein gene (PRNP) are an important factor influencing the susceptibility to prions and their rate of propagation. All reported cervid PRNP genotypes are affected by CWD. However, in each species, some polymorphisms are associated with lower attack rates and slower progression of the disease. This has potential consequences in terms of genetic selection, CWD diffusion and strain evolution. CWD also presents a zoonotic risk due to prions capacity to cross species barriers. This review summarizes our current understanding of CWD control, focusing on PRNP genetic, strain diversity and capacity to infect other animal species, including humans.
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However, the characterization of the infecting strain(s) in these natural conditions was not always assessed. This information is necessary for identifying spill over hosts and estimating the zoonotic potential [53]. Such breeding selection might also contribute to the emergence of new CWD strains [98].
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CWD positive animals with extended time before they succumb to disease likely represent a source of chronic prion shedding within populations and may contribute to environmental contamination.
veterinaryresearch.biomedcentral.com/articles/10.1186/s13567-021-00993-z
GENETICALLY MODIFIED DEER WON’T STOP CWD. HERE ARE 7 REASONS WHY
May 21, 2024 By: NDA Staff
deerassociation.com/genetically-modified-deer-wont-stop-cwd-here-are-7-reasons-why/
MEANWHILE, BACK AT THE RANCH$$$
Chronic Wasting Disease CWD TSE PRION DISEASE ENVIRONMENTAL FACTORS
CWD TSE ENVIRONMENTAL FACTORS
CWD TSE PRION CERVID ENVIRONMENTAL RISK FACTORS 2023
For what it's worth, Back around 2000, 2001, or so, I was corresponding with officials abroad during the bse inquiry, passing info back and forth on CJD and Nutritional Supplements and BSE here in the USA, and some officials from here inside USDA aphis FSIS et al, in fact helped me get into the USA 50 state emergency BSE conference call way back. That one was a doozy. But I always remember what “deep throat” as i called them, I never knew who they were, but I never forgot what i was told decades ago, amongst them was ;
Some unofficial information from a source on the inside looking out -
Confidential!!!!
As early as 1992-3 there had been long studies conducted on small pastures containing scrapie infected sheep at the sheep research station associated with the Neuropathogenesis Unit in Edinburgh, Scotland. Whether these are documented...I don't know. But personal recounts both heard and recorded in a daily journal indicate that leaving the pastures free and replacing the topsoil completely at least 2 feet of thickness each year for SEVEN years....and then when very clean (proven scrapie free) sheep were placed on these small pastures.... the new sheep also broke out with scrapie and passed it to offspring. I am not sure that TSE contaminated ground could ever be free of the agent!! A very frightening revelation!!!
---end personal email---end...tss
So, this is what we leave our children and grandchildren?..
"Additionally, we have determined that prion seeding activity is retained for at least fifteen years at a contaminated site following attempted remediation."
Detection of prions in soils contaminated by multiple routes
Stuart Siegfried Lichtenberg1,2 , Heather Inzalaco3 , Sam Thomas4 , Dan Storm5 , Dan Walsh6
1Department of Veterinary and Biomedical Sciences, University of Minnesota, St. Paul, Minnesota, U.S.A.
2Minnesota Center for Prion Research and Outreach, University of Minnesota, St. Paul, Minnesota, U.S.A.
3 Wisconsin Cooperative Wildlife Research Unit, Department of Forest and Wildlife Ecology, University of Wisconsin-Madison, Madison, Wisconsin, U.S.A
4Department of Soil Science, University of Wisconsin-Madison, Madison, Wisconsin, U.S.A.
5Wisconsin Department of Natural Resources, Eau Claire, Wisconsin, U.S.A.
6U.S. Geological Survey, Montana Cooperative Wildlife Research Unit, University of Montana, Missoula, Montana, U.S.A.
Aims: Free-ranging animals afflicted with transmissible spongiform encephalopathies frequently shed infectious prions into the broader environment. The quintessential example is chronic wasting disease, the TSE of cervids. Over the course of the disease, an infected animal will shed infectious prions in blood, urine, saliva, and feces. Upon death, the total prion load interred in the animal’s tissues will be deposited wherever the animal falls. This contamination creates substantial risk to naïve animals, and likely contributes to disease spread. Identification and quantification of prions at contamination hotspots is essential for any attempt at mitigation of environmental transmission.
Materials and Methods: Surfactant extraction of soils followed by precipitation yields a sample that is amenable to analysis by real-time quaking induced conversion. However, differences in extraction yield are apparent depending on the properties of the matrix from which the prions are being extracted, principally soil clay content.
Results: We are able to detect prion seeding activity at multiple types of environmental hotspots, including carcass sites, contaminated captive facilities, and scrapes (i.e. urine and saliva). Differences in relative prion concentration vary depending on the nature and source of the contamination. Additionally, we have determined that prion seeding activity is retained for at least fifteen years at a contaminated site following attempted remediation.
Conclusions: Detection of prions in the environment is of the utmost importance for controlling chronic wasting disease spread. Here, we have demonstrated a viable method for detection of prions in complex environmental matrices. However, it is quite likely that this method underestimates the total infectious prion load in a contaminated sample, due to incomplete recovery of infectious prions. Further refinements are necessary for accurate quantification of prions in such samples, and to account for the intrinsic heterogeneities found in the broader environment.
Funded by: Wisconsin Department of Natural Resources
=====end
Prion 2023 Abstracts
prion2023.org/wp-content/uploads/2023/10/Meeting-book-final-version2.pdf
Artificial mineral sites that pre-date endemic chronic wasting disease become prion hotspots
Heather N'te Inzalaco1,1, Marie L. Gilbertson1, Stephanie J. Katircioglu1, Kenny Lepard2, Jordan McEarl2, Austin Bibb2, Jeremy Dennison2, Dan Grove3, Allen Houston4, Dan J. Storm5, Dan P. Walsh6, Wendy C. Turner7, Stuart S. Lichtenberg8 1Wisconsin Cooperative Wildlife Research Unit, Department of Forest and Wildlife Ecology, University of Wisconsin, Madison, Madison, USA. 2Tennessee Wildlife Resources Agency, Jackson, USA. 3University of Tennessee Extension, Nashville, USA. 4University of Tennessee -Knoxville, School of Forest, Wildlife, and Fisheries, Ames Research and Education Center, Grand Junction, USA. 5Wisconsin Department of Natural Resources, Eau Claire, USA. 6U.S. Geological Survey, Montana Cooperative Wildlife Research Unit, Department of Ecosystem and Conservation Sciences, University of Montana, Missoula, USA. 7U.S. Geological Survey, Wisconsin Cooperative Wildlife Research Unit, Department of Forest and Wildlife Ecology, University of Wisconsin – Madison, Madison, USA. 8Department of Veterinary and Biomedical Sciences, University of Minnesota, Minnesota, USA
Abstract
Chronic wasting disease (CWD) is a highly contagious, fatal neurodegenerative disease caused by infectious prions (PrPCWD) affecting wild and captive cervids. As CWD continues to spread broadly over North America, factors influencing geographic expansion remain poorly understood. CWD-infected cervids shed infectious prions in urine, feces, and saliva. Activities that result in cervids aggregating and shedding PrPCWD may result in ‘hot spots’ of environmental PrPCWD deposition, however empirical data regarding the impact of deer attractants on environmental PrPCWD deposition is lacking. Filling this knowledge gap could inform deer and disease management. In 2018, the southwest region of Tennessee, U.S.A. experienced a CWD outbreak. The Ames Research and Educational Center property, centrally located within the CWD zone of southwest Tennessee, contains 49 historical mineral supplementation sites that were decommissioned in 2012. Here, we demonstrate that 32 of the 49 (65%) mineral sites within Ames established prior to the regional CWD outbreak, serve as foci of environmental PrPCWD contamination. Detection of PrPCWD in soils from these artificial mineral sites was dependent on site-specific management efforts. Soil physical properties were very similar across sites and no correlation between PrPCWD detection and soil physical properties was found. The detection of PrPCWD in soils at attractant sites within an endemic CWD zone significantly advances our understanding of environmental PrPCWD accumulation dynamics, providing valuable information for advancing adaptive CWD management approaches.
int-cwd-sympo.org/wp-content/uploads/2023/06/final-agenda-with-abstracts.pdf
9 Carrot plants as potential vectors for CWD transmission.
Paulina Soto1,2, Francisca Bravo-Risi1,2, Claudio Soto1, Rodrigo Morales1,2
1Department of Neurology, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, USA. 2Universidad Bernardo O’Higgins, Santiago, Chile
***> We show that edible plant components can absorb prions from CWD-contaminated soils and transport them to their aerial parts.
***> Our results indicate that edible plants could participate as vectors of CWD transmission
=====
intcwdsympo.files.wordpress.com/2023/06/final-agenda-with-abstracts.pdf?force_download=true
***> Infectious agent of sheep scrapie may persist in the environment for at least 16 years
***> Nine of these recurrences occurred 14–21 years after culling, apparently as the result of environmental contamination, but outside entry could not always be absolutely excluded.
JOURNAL OF GENERAL VIROLOGY Volume 87, Issue 12
Infectious agent of sheep scrapie may persist in the environment for at least 16 years Free
www.microbiologyresearch.org/content/journal/jgv/10.1099/vir.0.82011-0
Rapid recontamination of a farm building occurs after attempted prion removal
First published: 19 January 2019 doi.org/10.1136/vr.105054
The data illustrates the difficulty in decontaminating farm buildings from scrapie, and demonstrates the likely contribution of farm dust to the recontamination of these environments to levels that are capable of causing disease. snip...
This study clearly demonstrates the difficulty in removing scrapie infectivity from the farm environment. Practical and effective prion decontamination methods are still urgently required for decontamination of scrapie infectivity from farms that have had cases of scrapie and this is particularly relevant for scrapie positive goatherds, which currently have limited genetic resistance to scrapie within commercial breeds.24 This is very likely to have parallels with control efforts for CWD in cervids.
bvajournals.onlinelibrary.wiley.com/doi/abs/10.1136/vr.105054
***>This is very likely to have parallels with control efforts for CWD in cervids.
pubmed.ncbi.nlm.nih.gov/30602491/
Front. Vet. Sci., 14 September 2015 | doi.org/10.3389/fvets.2015.00032
Objects in contact with classical scrapie sheep act as a reservoir for scrapie transmission
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.
journal.frontiersin.org/article/10.3389/fvets.2015.00032/full
172. Establishment of PrPCWD extraction and detection methods in the farm soil
Conclusions: Our studies showed that PrPCWD persist in 0.001% CWD contaminated soil for at least 4 year and natural CWD-affected farm soil. When cervid reintroduced into CWD outbreak farm, the strict decontamination procedures of the infectious agent should be performed in the environment of CWD-affected cervid habitat.
www.tandfonline.com/doi/full/10.1080/19336896.2019.1615197
Plants as vectors for environmental prion transmission
Published: November 09, 2023DOI: doi.org/10.1016/j.isci.2023.108428
Advertisement Highlights
• Abnormal prion protein can enter the roots of plants
• Plants can translocate detectable levels of prions to aerial tissues
•Animals exposed to prion-contaminated plant tissues can acquire disease
•Contaminated plants may represent a route of prion exposure
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Nonetheless, our finding of accumulation of two prion strains by a variety of plants grown hydroponically, in agar, or on soil supports the potential for plants to acquire CWD, scrapie, or other prions from the environment and transmit prion disease to susceptible hosts, making plants a plausible vector for prion diseases in wildlife, livestock, and humans. The potential for plants to serve as vectors for prion disease has implications for the disposal of infected carcasses, grazing practices, and the use and transport of potentially contaminated crop materials.
www.cell.com/iscience/pdf/S2589-0042(23)02505-1.pdf
www.cell.com/iscience/fulltext/S2589-0042(23)02505-1?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS2589004223025051%3Fshowall%3Dtrue
Carrot plants as potential vectors for CWD transmission.
The PMCA analysis demonstrated CWD seeding activity in soils contaminated with CWD prions and in carrot plants (leaves and roots) grown on them. Bioassays showed that both plants and roots contained CWD prions sufficiently to induce disease. As expected, animals treated with prion-infected soils developed prion disease at shorter incubation periods (and complete attack rates) compared to plant components. We show that edible plant components can absorb prions from CWD-contaminated soils and transport them to their aerial parts. Our results indicate that edible plants could participate as vectors of CWD transmission.
intcwdsympo.files.wordpress.com/2023/06/final-agenda-with-abstracts.pdf?force_download=true
“In addition, hay and straw from the United States and Canada must be accompanied by a certificate from a public veterinarian that the product has been harvested in states or provinces where Chronic Wasting Disease has not been detected on deer.”
Regulation No. 1599 of 2018 on additional requirements for the import of hay and straw for used for animal feed.
Country Norway
Type of law Regulation
Source
FAO , FAOLEX
In addition, hay and straw from the United States and Canada must be accompanied by a certificate from a public veterinarian that the product has been harvested in states or provinces where Chronic Wasting Disease has not been detected on deer.
faolex.fao.org/docs/pdf/nor189761.pdf
Chronic wasting disease detection in environmental and biological samples from a taxidermy site
Paulina Sotoa,b, J. Hunter Reedc, Mitch Lockwoodc, and Rodrigo Moralesa,b
aDepartment of Neurology, McGovern Medical School, University of Texas Health Science Center at Houston, Texas, USA; bUniversidad Bernardo O’Higgins, Santiago, Chile; cTexas Parks and Wildlife Department, Texas, USA
Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy affecting captive and free-ranging cervids (e.g., mule deer, white-tailed deer, elk, reindeer, and moose). Nowadays, CWD is widely distributed in North America. It is suggested that CWD spreads due to direct animal contact or through exposure to contaminated environments previously inhabited by infected animals. CWD may also be spread through the movement of infected animals and carcasses. Taxidermy practices involve processing deer tissues (or whole animal carcasses). In many cases, the CWD status of processed animals is unknown. This can generate risks of disease spread and transmission. Taxidermy practices include different steps involving physical, chemical, and biological procedures. Without proper tissue handling or disposal practices, taxidermist facilities may become a focus of prion infectivity.
Aims: In this study, we evaluated the presence of infectious prions in a taxidermy facility believed to be exposed to CWD. Detection was performed using the Protein Misfolding Cyclic Amplification (PMCA) technique in biological and inert environmental samples.
Methods: We collected biological and environmental samples (plants, soils, insects, excreta, and others) from a taxidermy facility, and we tested these samples using the PMCA technique. In addition, we swabbed different surfaces possibly exposed to CWD-infected animals. For the PMCA reaction, we directly used a swab piece or 10 µL of 20% w/v homogenized samples.
Results: The PMCA analysis demonstrated CWD seeding activity in some of the components of this facility, including insects involved in head processing, soils, and a trash dumpster.
Conclusions: Different areas of this property were used for various taxidermy procedures. We were able to detect the presence of prions in i) soils that were in contact with the heads of dead animals, ii) insects involved in the cleaning of skulls, and iii) an empty dumpster where animal carcasses were previously placed. This is the first report demonstrating that swabbing is a helpful method to screen for prion infectivity on surfaces potentially contaminated with CWD. These findings are relevant as this swabbing and amplification strategy may be used to evaluate the disease status of other free-ranging and captive settings where there is a concern for CWD transmissions, such as at feeders and water troughs with CWD-exposed properties. This approach could have substantial implications for free-ranging cervid surveillance as well as in epidemiological investigations of CWD.
Funded by: USDA
Grant number: AP20VSSPRS00C143
PRION 2022 ABSTRACTS, AND A BIG THANK YOU TO On behalf of the Prion2020/2022 Congress Organizing Committee and the NeuroPrion Association, we heartily invite you to join us for the International Conference Prion2020/2022 from 13.-16. September 2022 in Göttingen.
Prion 2022 Conference abstracts: pushing the boundaries
www.tandfonline.com/doi/full/10.1080/19336896.2022.2091286
Large-scale PMCA screening of retropharyngeal lymph nodes and in white-tailed deer and comparisons with ELISA and IHC: the Texas CWD study
Rebeca Benaventea, Paulina Sotoa, Mitch Lockwoodb, and Rodrigo Moralesa aDepartment of Neurology, McGovern Medical School, University of Texas Health Science Center at Houston, Texas, USA; bTexas Park and Wildlife Department, Texas, USA
Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy that affects various species of cervids, and both free-ranging and captive animals. Until now, CWD has been detected in 3 continents: North America, Europe, and Asia. CWD prevalence in some states may reach 30% of total animals. In Texas, the first case of CWD was reported in a free-range mule deer in Hudspeth and now it has been detected in additional 14 counties. Currently, the gold standard techniques used for CWD screening and detection are ELISA and immunohistochemistry (IHC) of obex and retropharyngeal lymph nodes (RPLN). Unfortunately, these methods are known for having a low diagnostic sensitivity. Hence, many CWD-infected animals at pre-symptomatic stages may be misdiagnosed. Two promising in vitro prion amplification techniques, including the real-time quaking-induced conversion (RT-QuIC) and the protein misfolding cyclic amplification (PMCA) have been used to diagnose CWD and other prion diseases in several tissues and bodily fluids. Considering the low cost and speed of RT-QuIC, two recent studies have communicated the potential of this technique to diagnose CWD prions in RPLN samples. Unfortunately, the data presented in these articles suggest that identification of CWD positive samples is comparable to the currently used ELISA and IHC protocols. Similar studies using the PMCA technique have not been reported.
Aims: Compare the CWD diagnostic potential of PMCA with ELISA and IHC in RPLN samples from captive and free-range white-tailed deer. Material and Methods: In this study we analyzed 1,003 RPLN from both free-ranging and captive white-tailed deer collected in Texas. Samples were interrogated with the PMCA technique for their content of CWD prions. PMCA data was compared with the results obtained through currently approved techniques.
Results: Our results show a 15-fold increase in CWD detection in free-range deer compared with ELISA. Our results unveil the presence of prion infected animals in Texas counties with no previous history of CWD. In the case of captive deer, we detected a 16% more CWD positive animals when compared with IHC. Interestingly, some of these positive samples displayed differences in their electroforetic mobilities, suggesting the presence of different prion strains within the State of Texas.
Conclusions: PMCA sensitivity is significantly higher than the current gold standards techniques IHC and ELISA and would be a good tool for rapid CWD screening.
Funded by: USDA
Grant number: AP20VSSPRS00C143
PRION 2022 ABSTRACTS, AND A BIG THANK YOU TO On behalf of the Prion2020/2022 Congress Organizing Committee and the NeuroPrion Association, we heartily invite you to join us for the International Conference Prion2020/2022 from 13.-16. September 2022 in Göttingen.
Prion 2022 Conference abstracts: pushing the boundaries
www.tandfonline.com/doi/full/10.1080/19336896.2022.2091286
Shedding of Chronic Wasting Disease Prions in Multiple Excreta Throughout Disease Course in White-tailed Deer
Nathaniel D. Denkersa, Erin E. McNultya, Caitlyn N. Krafta, Amy V. Nallsa, Joseph A. Westricha, Wilfred Goldmannb, Candace K. Mathiasona, and Edward A. Hoovera
aPrion Research Center, College of Veterinary Medicine and Biological Sciences, Department of Microbiology, Immunology, and Pathology; Colorado State University, Fort Collins, CO, USA; bDivision of Infection and Immunity, The Roslin Institute and the Royal Dick School of Veterinary Studies, University of Edinburgh, Midlothian, UK
Aims: Chronic wasting disease (CWD) now infects cervids in South Korea, North America, and Scandinavia. CWD is unique in its efficient transmission and shedding of prions in body fluids throughout long course infections. Questions remain as to the magnitude of shedding and the route of prion acquisition. As CWD continues to expand, the need to better understand these facets of disease becomes more pertinent. The purpose of the studies described was to define the longitudinal shedding profile of CWD prions in urine, saliva, and feces throughout the course of infection in white-tailed deer.
Material and Methods: Twelve (12) white-tailed deer were inoculated with either 1 mg or 300ng of CWD. Urine, saliva, and feces were collected every 3-month post-inoculation (MPI) throughout the study duration. Cohorts were established based on PNRP genotype: codon 96 GG (n = 6) and alternate codons 96 GS (n = 5) & 103NT (n = 1). Urine and saliva were analyzed using iron-oxide magnetic extraction (IOME) and real-time quaking induced conversion (RT-QuIC)(IQ). Feces were subjected to IOME, followed by 4 rounds protein misfolding cyclic amplification (PMCA) with products analyzed by RT-QuIC (IPQ). To determine whether IPQ may be superior to IQ, a subset of urine and saliva were also tested by IPQ. Results were compared with clinical disease status.
Results: Within the 96 GG cohort, positive seeding activity was detected in feces from all deer (100%), in saliva from 5 of 6 (83%), and in urine from 4 of 6 (66%). Shedding in all excreta occurred at, or just after, the first positive tonsil biopsy result. In the 96 GS/103NT cohort, positive seeding activity could be detected in feces from 3 of 6 (50%) deer, saliva in 2 of 6 (33%), and urine in 1 of 6 (16%). Shedding in excreta was detected >5 months after the first tonsil positive result. Four of six 96 GG deer developed clinical signs of CWD, whereas only 2 of the 96 GS/103NT did. Shedding was more frequently detected in deer with clinical disease. The IPQ protocol did not significantly improve detection in saliva or urine samples, however, it significantly augmented detection in feces by eliminating non-specific background commonly experienced with IQ. Negative control samples remained negative in samples tested.
Conclusions: These studies demonstrate: (a) CWD prion excretion occurs throughout infection; (2) PRNP genotype (GG≫GS/NT) influences the excreta shedding; and (3) detection sensitivity in excreta can vary with different RT-QuIC protocols. These results provide a more complete perspective of prion shedding in deer during the course of CWD infection.
Funded by: National Institutes of Health (NIH)
Grant number: RO1-NS061902-09 R to EAH, PO1-AI077774 to EAH, and R01-AI112956-06 to CKM
Acknowledgement: We abundantly thank Sallie Dahmes at WASCO and David Osborn and Gino D’Angelo at the University of Georgia Warnell School of Forestry and Natural Resources for their long-standing support of this work through provision of the hand-raised, CWD-free, white-tailed deer used in these studies
Carrot plants as potential vectors for CWD transmission
Paulina Sotoa,b, Francisca Bravo-Risia,b, Claudio Sotoa, and Rodrigo Moralesa,b
aDepartment of Neurology, McGovern Medical School, University of Texas Health Science Center at Houston, Texas, USA; bUniversidad Bernardo O’Higgins, Santiago, Chile
Prion diseases are infectious neurodegenerative disorders afflicting humans and other mammals. These diseases are generated by the misfolding of the cellular prion protein into a disease-causing isoform. Chronic wasting disease (CWD) is a prevalent prion disease affecting cervids (captive and free-range). CWD is thought to be transmitted through direct animal contact or by indirect exposure to contaminated environments. Many studies have shown that infectious prions can enter the environment through saliva, feces, or urine from infected animals and decaying carcasses. However, we do not fully understand the specific contribution of each component to disease transmission events. Plants are logical environmental components to be evaluated since they grow in environments contaminated with CWD prions and are relevant for animal and human nutrition.
Aims: The main objective of this study is to study whether prions are transported to the roots and leaves of carrots, an edible plant commonly used in the human diet and as deer bait.
Methods: We have grown carrot plants in CWD-infected soils. After 90 days, we harvested the carrots and separated them from the leaves. The experiment was controlled by growing plants in soil samples treated with brain extracts from healthy animals. These materials were interrogated for their prion seeding activity using the Protein Misfolding Cyclic Amplification (PMCA) technique. Infectivity was evaluated in mouse bioassays (intracerebral injections in Tg1536 mice). The animals were sacrificed when they showed established signs of prion disease. Animals not displaying clinical signs were sacrificed at 600 days post-inoculation.
Results: The PMCA analysis demonstrated CWD seeding activity in soils contaminated with CWD prions, as well as in carrot plants (leaves and roots) grown on them. Bioassays demonstrated that both leaves and roots contained CWD prions in sufficient quantities to induce disease (92% attack rate). As expected, animals treated with prion-infected soils developed prion disease at shorter incubation periods (and complete attack rates) compared to plant components. Animals treated with soil and plant components exposed with CWD-free brain extracts did not display prion-associated clinical signs or evidence of sub-clinical prion infection.
Conclusions: We show that edible plant components can absorb prions from CWD contaminated soils and transport them to their aerial parts. Our results indicate that plants could participate as vectors of CWD transmission. Importantly, plants designated for human consumption represent a risk of introducing CWD prions into the human food chain.
Funded by: NIH
Grant number: R01AI132695
www.tandfonline.com/doi/full/10.1080/19336896.2022.2091286
October 6th-12th, 126th Meeting 2022 Resolutions
RESOLUTION NUMBER: 30 Approved
SOURCE: COMMITTEE ON WILDLIFE
SUBJECT MATTER: Chronic Wasting Disease Carcass Disposal Dumpster Management and Biosecurity
BACKGROUND INFORMATION:
State and tribal wildlife agencies may identify collection points (dumpsters) within an identified chronic wasting disease (CWD) management zone for the disposal of hunter-harvested cervid carcasses to remove potentially infected carcasses off the landscape for disposal by an approved method (Gillin & Mawdsley, 2018, chap.14). However, depending on their placement and maintenance these dumpsters could potentially increase the risk of CWD transmission.
In several different states, photographic evidence has shown dumpsters in state identified CWD management zones overflowing with deer carcasses and limbs scattered on the land nearby. This could provide an opportunity for scavengers to potentially move infected carcass material to non-infected zones or increase contamination of the ground material around the dumpster’s location.
Federal guidance does not explicitly address uniform standards for collection locations for carcasses of free-ranging cervids; however, the United States Department of Agriculture, Animal and Plant Health Inspection Service, Veterinary Services Program Standards on CWD outlines procedures for carcass disposal, equipment sanitation, and decontamination of premises for captive cervid facilities.
RESOLUTION:
The United States Animal Health Association urges the Association of Fish and Wildlife Agencies (AFWA), Wildlife Health Committee to further refine the AFWA Technical Report on Best Management Practices for Prevention, Surveillance, and Management of Chronic Wasting Disease; Chapter 14, Carcass Disposal to address the placement and management of chronic wasting disease carcass disposal dumpsters or other carcass collection containers.
Reference:
1. Gillin, Colin M., and Mawdsley, Jonathan R. (eds.). 2018. AFWA Technical Report on Best Management Practices for Surveillance, Management and Control of Chronic Wasting Disease. Association of Fish and Wildlife Agencies, Washington, D. C. 111 pp.
www.usaha.org/upload/Resolution/2022/2022_Resolution_30_CWD_Dumpste.pdf
Trucking CWD TSE PrP
Friday, December 14, 2012
DEFRA U.K. What is the risk of Chronic Wasting Disease CWD being introduced into Great Britain? A Qualitative Risk Assessment October 2012
snip...
The rate of transmission of CWD has been reported to be as high as 30% and can approach 100% among captive animals in endemic areas (Safar et al., 2008).
snip...
In summary, in endemic areas, there is a medium probability that the soil and surrounding environment is contaminated with CWD prions and in a bioavailable form. In rural areas where CWD has not been reported and deer are present, there is a greater than negligible risk the soil is contaminated with CWD prion.
snip...
In summary, given the volume of tourists, hunters and servicemen moving between GB and North America, the probability of at least one person travelling to/from a CWD affected area and, in doing so, contaminating their clothing, footwear and/or equipment prior to arriving in GB is greater than negligible. For deer hunters, specifically, the risk is likely to be greater given the increased contact with deer and their environment. However, there is significant uncertainty associated with these estimates.
snip...
Therefore, it is considered that farmed and park deer may have a higher probability of exposure to CWD transferred to the environment than wild deer given the restricted habitat range and higher frequency of contact with tourists and returning GB residents.
snip...
web.archive.org/web/20170404125557/http://webarchive.nationalarchives.gov.uk/20130822084033/http://www.defra.gov.uk/animal-diseases/files/qra_chronic-wasting-disease-121029.pdf
THE tse prion aka mad cow type disease is not your normal pathogen.
The TSE prion disease survives ashing to 600 degrees celsius, that’s around 1112 degrees farenheit.
you cannot cook the TSE prion disease out of meat.
you can take the ash and mix it with saline and inject that ash into a mouse, and the mouse will go down with TSE.
Prion Infected Meat-and-Bone Meal Is Still Infectious after Biodiesel Production as well.
the TSE prion agent also survives Simulated Wastewater Treatment Processes.
IN fact, you should also know that the TSE Prion agent will survive in the environment for years, if not decades.
you can bury it and it will not go away.
The TSE agent is capable of infected your water table i.e. Detection of protease-resistant cervid prion protein in water from a CWD-endemic area.
it’s not your ordinary pathogen you can just cook it out and be done
New studies on the heat resistance of hamster-adapted scrapie agent: Threshold survival after ashing at 600°C suggests an inorganic template of replication
www.pnas.org/content/97/7/3418.full
Prion Infected Meat-and-Bone Meal Is Still Infectious after Biodiesel Production
www.ncbi.nlm.nih.gov/pmc/articles/PMC2493038/
Detection of protease-resistant cervid prion protein in water from a CWD-endemic area
https://www.ncbi...nlm.nih.gov/pmc/articles/PMC2802782/pdf/prion0303_0171.pdf
Prions in Waterways
vimeo.com/898941380?fbclid=IwAR3Di7tLuU-iagCetdt4-CVPrOPQQrv037QS1Uxz0tX3z7BuvPeYlwIp7IY
A Quantitative Assessment of the Amount of Prion Diverted to Category 1 Materials and Wastewater During Processing
onlinelibrary.wiley.com/doi/10.1111/j.1539-6924.2012.01922.x/abstract
Rapid assessment of bovine spongiform encephalopathy prion inactivation by heat treatment in yellow grease produced in the industrial manufacturing process of meat and bone meals
bmcvetres.biomedcentral.com/track/pdf/10.1186/1746-6148-9-134.pdf
THURSDAY, FEBRUARY 28, 2019
BSE infectivity survives burial for five years with only limited spread
link.springer.com/content/pdf/10.1007%2Fs00705-019-04154-8.pdf
“Transmissible spongiform encephalopathy (TSE) agents have strain variations that influence disease phenotype and may affect the potential for interspecies transmission. Since deer and sheep may use the same grazing land, it is important to understand the potential transmission of TSEs between these species. The US scrapie isolate (No.13-7) had a 100% attack rate in white-tailed deer after oronasal challenge.”
www.ars.usda.gov/research/publications/publication/?seqNo115=405929
TUESDAY, JANUARY 16, 2024
CIDRAP launches international effort to prepare for possible chronic wasting disease spillover
Chronic Wasting Disease CWD TSE Prion Spillover to other Species, What If?
chronic-wasting-disease.blogspot.com/2024/01/cidrap-launches-international-effort-to.html
CWD, Plants, oh my…
www.cidrap.umn.edu/chronic-wasting-disease/plants-can-take-cwd-causing-prions-soil-lab-what-happens-if-they-are-eaten
THE following study is another band aid approach, to something that needed a tourniquet decades ago. instead of fixing the problem, let's cater to the industry some more...terry
Investigating potential inhibitory roles of organic copper and zinc in CWD prion protein misfolding and propagation
Joseph Hediger1, Peter Larsen2, Jason Bartz3, Randy DeYoung1, David Hewitt1, Mitch Lockwood4, Alynn Martin1, J. Hunter Reed4, Marc Schwabenlander2, Tiffany Wolf5, Michael Cherry1 1Caesar Kleberg Wildlife Research Institute, Kingsville, TX, USA. 2Minnesota Center for Prion Research and Outreach, St. Paul, MN, USA. 3Creighton University, Omaha, NE, USA. 4Texas Parks and Wildlife Department, Austin, TX, USA. 5University of Minnesota, St. Paul, MN, USA
Abstract
Positive cases of Chronic Wasting Disease (CWD) are spreading rapidly across the United States, Canada, and Europe. Although a treatment is currently unavailable for CWD, there is potential for molecules to bind to misfolded prions preventing or slowing subsequent protein misfolding. In a rodent model, orally administered copper inhibited the misfolding and propagation of infectious proteins. However, it is yet unknown how mineral status influences disease progression in cervids. We are working to determine if copper (Cu-AA) and zinc (Zn-AA) concentrations in target organs influence the propagation of misfolded CWD prions (PrPcwd). To do this we harvested 150 mature white-tailed deer (Odocoileus virginianus) spanning a gradient of Cu-AA and Zn-AA bioavailability in Texas, USA. Samples, including liver, brain, distal ilium, medial retropharyngeal lymph nodes, and tongue, were collected from 1) deer in South Texas with natural nutrition, 2) free-ranging deer with access to supplemental feed enhanced with Cu-AA and Zn-AA, and 3) captive deer fed exclusively feed with Cu-AA and Zn-AA supplementation. We will use prion misfolding cyclic amplification to evaluate the role of Cu-AA and Zn-AA concentrations in brain and lymphoid tissue in reducing PrPcwd, while accounting for CWD status and genetic susceptibility to CWD. This research has the potential to identify molecules that may serve as novel management options for CWD treatment and prevention.
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Genomic Predictions For Differential Susceptibility to Chronic Wasting Disease in Farmed U.S. White-tailed Deer
Christopher Seabury1, Tracy Nichols2
1Texas A&M University, College Station, USA. 2USDA APHIS Veterinary Services, Fort Collins, USA
Abstract
Despite advanced management practices, diagnostic surveillance, and depopulation of positive herds, the geographic expansion of chronic wasting disease (CWD) in U.S. white-tailed deer (Odocoileus virginianus; hereafter WTD) remains largely unabated. Therefore, a critical need exists to identify novel strategies that reduce the prevalence of CWD. Herein, we deploy a custom single nucleotide polymorphism (SNP) array to perform the largest genome-wide association study for CWD in farmed U.S. WTD to date; thereby confirming PRNP codon 96 as the largest-effect region of the WTD genome (P-value ≤ 5.99e-13; Proportion of Variance Explained ≥ 0.032). However, beyond PRNP, 25 significant SNPs (P-value ≤ 5e-05) also were detected, thereby implicating ≥ 25 unique positional candidate genes; many of which have been directly implicated in aspects Alzheimer’s, Parkinson’s, and various prion diseases. Our genome-wide association analyses unequivocally indicate that differential susceptibility to CWD and variation in natural disease progression have trait architectures comprised of very few moderate or large-effect genetic components, and many small-effect genetic components; which is consistent with most polygenic traits. Interestingly, genomic relationship matrix heritability estimates were high for both differential susceptibility to CWD (h2 = 0.611 ± 0.056), and for variation in natural disease progression (h2 = 0.589 ± 0.069); indicating that the majority of the variation in these traits can be explained by genetic differences. Likewise, heritability estimates produced for differential susceptibility to CWD on the liability scale, with adjustment for ascertainment of the case samples (using the weighted mean prevalence) were also high (h2 ≥ 0.857 ± 0.082); only further confirming that the majority of the variation in CWD susceptibility can be explained by genetic differences. To investigate the potential impact of deploying genomic predictions as a management-level decision support tool intended to reduce the prevalence of CWD in farmed U.S. WTD, we used genomic best linear unbiased prediction in conjunction with k-fold cross validation (k = 3; k = 5) and random sampling across 50 iterations for multiple models. Across all model fits and iterations, mean genomic prediction accuracies were high (≥ 0.81). For comparison, we also performed leave-one-out cross-validation; which produced similar results related to genomic prediction accuracy. To further evaluate the utility of a genomic prediction program for CWD management-level decision support, a blind validation was administered by USDAAPHIS. The mean sensitivity of the blind genomic predictions was ≥ 0.87. Collectively, our analyses indicate that WTD breeding programs utilizing genomic predictions for CWD management-level decisions such as genetic improvement through selective breeding, and/or the targeted removal of moderate and highly susceptible WTD, would be expected to reduce the prevalence of CWD.
intcwdsympo.files.wordpress.com/2023/06/final-agenda-with-abstracts.pdf?force_download=true
***> Price of TSE Prion Poker goes up substantially, all you cattle ranchers and such, better pay close attention here...terry
Prion Conference 2023
Transmission of the chronic wasting disease agent from elk to cattle after oronasal exposure
Justin Greenlee, Jifeng Bian, Zoe Lambert, Alexis Frese, and Eric Cassmann Virus and Prion Research Unit, National Animal Disease Center, USDA-ARS, Ames, IA, USA
Aims: The purpose of this study was to determine the susceptibility of cattle to chronic wasting disease agent from elk.
Materials and Methods: Initial studies were conducted in bovinized mice using inoculum derived from elk with various genotypes at codon 132 (MM, LM, LL). Based upon attack rates, inoculum (10% w/v brain homogenate) from an LM132 elk was selected for transmission studies in cattle. At approximately 2 weeks of age, one wild type steer (EE211) and one steer with the E211K polymorphism (EK211) were fed 1 mL of brain homogenate in a quart of milk replacer while another 1 mL was instilled intranasally. The cattle were examined daily for clinical signs for the duration of the experiment. One steer is still under observation at 71 months post-inoculation (mpi).
Results: Inoculum derived from MM132 elk resulted in similar attack rates and incubation periods in mice expressing wild type or K211 bovine PRNP, 35% at 531 days post inoculation (dpi) and 27% at 448 dpi, respectively. Inoculum from LM132 elk had a slightly higher attack rates in mice: 45% (693 dpi) in wild type cattle PRNP and 33% (468) in K211 mice. Inoculum from LL132 elk resulted in the highest attack rate in wild type bovinized mice (53% at 625 dpi), but no K211 mice were affected at >700 days. At approximately 70 mpi, the EK211 genotype steer developed clinical signs suggestive of prion disease, depression, low head carriage, hypersalivation, and ataxia, and was necropsied. Enzyme immunoassay (IDEXX) was positive in brainstem (OD=4.00, but non-detect in retropharyngeal lymph nodes and palatine tonsil. Immunoreactivity was largely limited to the brainstem, midbrain, and cervical spinal cord with a pattern that was primarily glia-associated.
Conclusions: Cattle with the E211K polymorphism are susceptible to the CWD agent after oronasal exposure of 0.2 g of infectious material.
"Cattle with the E211K polymorphism are susceptible to the CWD agent after oronasal exposure of 0.2 g of infectious material."
=====end
Strain characterization of chronic wasting disease in bovine-PrP transgenic mice
Conclusions: Altogether, these results exhibit the diversity of CWD strains present in the panel of CWD isolates and the ability of at least some CWD isolates to infect bovine species. Cattle being one of the most important farming species, this ability represents a potential threat to both animal and human health, and consequently deserves further study.
"Altogether, these results exhibit the diversity of CWD strains present in the panel of CWD isolates and the ability of at least some CWD isolates to infect bovine species. Cattle being one of the most important farming species, this ability represents a potential threat to both animal and human health, and consequently deserves further study."
=====end
prion2023.org/wp-content/uploads/2023/10/Meeting-book-final-version2.pdf
Cattle with the EK211 PRNP polymorphism are susceptible to the H-type bovine spongiform encephalopathy agent from either E211K or wild type donors after oronasal inoculation
Justin J. Greenleea, Eric D. Cassmanna, S. Jo Moorea,b, and M. Heather West Greenleec
aVirus and Prion Research Unit, National Animal Disease Center, ARS, United States Department of Agriculture, Ames, IA, USA; bOak Ridge Institute for Science and Education (ORISE), U.S. Department of Energy, Oak Ridge, TN, US; cDepartment of Biomedical Sciences, Iowa State University College of Veterinary Medicine, Ames, IA, US
Aims: In 2006, a case of H-type bovine spongiform encephalopathy (H-BSE) was reported in a cow with a previously unreported prion protein polymorphism (E211K). The E211K polymorphism is heritable and homologous to the E200K mutation in humans that is the most frequent PRNP mutation associated with familial Creutzfeldt-Jakob disease. Although the prevalence of the E211K polymorphism is low, cattle carrying the K211 allele develop H-type BSE with a rapid onset after experimental inoculation by the intracranial route. The purpose of this study was to investigate whether the agents of H-type BSE or H-type BSE associated with the E211K polymorphism transmit to wild type cattle or cattle with the K211 allele after oronasal exposure.
Material and Methods: Wild type (EE211) or heterozygous (EK211) cattle were oronasally inoculated with the H-BSE agent from either the US 2004 case (wild type donor; n = 3) or from the US 2006 case with the E211K polymorphism (n = 4). Cattle were observed daily throughout the course of the experiment for the development of clinical signs. When signs were noted, animals were euthanized and necropsied. Cattle were confirmed positive for abnormal BSE prions by enzyme immunoassay (EIA; Idexx HerdChek BSE Ag Test), anti-PrP immunohistochemistry (IHC) on brainstem, and microscopic examination for vacuolation.
Results: Three-out-of-four (75%) calves with the EK211 genotype developed clinical signs of H-BSE including inattentiveness, loss of body condition, weakness, ataxia, and muscle fasciculations and were euthanized. Two of the positive EK211 steers received H-BSE US 2004 inoculum (Incubation Period (IP): 59.3 and 72.3 months) while the other positive steer received the E211K H-BSE inoculum (IP: 49.7 months). EIA confirmed that abundant misfolded protein (O.D. 2.57–4.0) in the brainstem, and IHC demonstrated PrPScthroughout the brain. All wild type recipient cattle and a single EK211 steer remained asymptomatic for the duration of the experiment (approximately 7 years post-inoculation) and no abnormal prion protein was detected in these cattle by EIA.
Conclusions: This study demonstrates that the H-type BSE agent is transmissible by the oronasal route. Cattle with the EK211 genotype are oronasally susceptible to small doses of the H-BSE agent from either EK211 or EE211 (wild type) donors. Wild-type EE211 cattle remained asymptomatic for the duration of the experiment with this small dose (0.1 g) of inoculum. These results reinforce the need for ongoing surveillance for classical and atypical BSE to minimize the risk of potentially infectious tissues entering the animal or human food chains.
Funded by: US Department of Agriculture
www.tandfonline.com/doi/full/10.1080/19336896.2022.2091286
fdabse589.blogspot.com/2023/11/food-and-drug-administrations-bse-feed.html
Control of Chronic Wasting Disease OMB Control Number: 0579-0189APHIS-2021-0004 Singeltary Submission
www.regulations.gov/comment/APHIS-2021-0004-0002
downloads.regulations.gov/APHIS-2021-0004-0002/attachment_1.pdf
Docket No. APHIS-2018-0011 Chronic Wasting Disease Herd Certification
www.regulations.gov/document/APHIS-2018-0011-0003
downloads.regulations.gov/APHIS-2018-0011-0003/attachment_1.pdf
APHIS Indemnity Regulations [Docket No. APHIS-2021-0010] RIN 0579-AE65 Singeltary Comment Submission
Comment from Singeltary Sr., Terry
Posted by the Animal and Plant Health Inspection Service on Sep 8, 2022
www.regulations.gov/comment/APHIS-2021-0010-0003
downloads.regulations.gov/APHIS-2021-0010-0003/attachment_1.pdf
Docket No. FDA-2003-D-0432 (formerly 03D-0186) Use of Material from Deer and Elk in Animal Feed
PUBLIC SUBMISSION
Comment from Terry Singeltary Sr.
Posted by the Food and Drug Administration on May 17, 2016 Comment
Docket No. FDA-2003-D-0432 (formerly 03D-0186) Use of Material from Deer and Elk in Animal Feed Singeltary Submission
www.regulations.gov/comment/FDA-2003-D-0432-0011
www.regulations.gov/docket/FDA-2003-D-0432
Singeltary comments;
31 Jan 2015 at 20:14 GMT
Ruminant feed ban for cervids in the United States?
web.archive.org/web/20150722000538/http://www.plosone.org/annotation/listThread.action?root=85351
CHRONIC WASTING DISEASE CWD TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY TSE PRION DISEASE ZOONOSIS, ZOONOTIC
“If CWD in humans is found to be contagious and transmissible among humans, as it is in cervids [57], the spread of the disease within humans might become endemic.”
PART 2. TPWD CHAPTER 65. DIVISION 1. CWD
31 TAC §§65.82, 65.85, 65.88
The Texas Parks and Wildlife Commission in a duly noticed meeting on May 25, 2023 adopted amendments to 31 TAC §§65.82, 65.85, and §65.88, concerning Disease Detection and Response, without changes to the proposed text as published in the April 21, 2023, issue of the Texas Register (48 TexReg 2048). The rules will not be republished.
Currently, there is scientific evidence to suggest that CWD has zoonotic potential; however, no confirmed cases of CWD have been found in humans.
www.sos.texas.gov/texreg/archive/June302023/Adopted%20Rules/31.NATURAL%20RESOURCES%20AND%20CONSERVATION.html#57
17 DETECTION OF CHRONIC WASTING DISEASE PRIONS IN PROCESSED MEATS.
Rebeca Benavente1, Francisca Bravo1,2, Paulina Soto1,2, J. Hunter Reed3, Mitch Lockwood3, Rodrigo Morales1,2
1Department of Neurology, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, USA. 2Universidad Bernardo O’Higgins, Santiago, Chile. 3Texas Parks and Wildlife, Austin, USA
Abstract
The zoonotic potential of chronic wasting disease (CWD) remains unknown. Currently, there are no known natural cases of CWD transmission to humans but increasing evidence suggests that the host range of CWD is not confined only to cervid species. Alarmingly, recent experimental evidence suggests that certain CWD isolates can induce disease in non-human primates. While the CDC strongly recommends determining CWD status in animals prior to consumption, this practice is voluntary. Consequently, it is plausible that a proportion of the cervid meat entering the human food chain may be contaminated with CWD. Of additional concern is that traditional diagnostic techniques used to detect CWD have relatively low sensitivity and are only approved for use in tissues other than those typically ingested by humans. In this study, we analyzed different processed meats derived from a pre-clinical, CWD-positive free-ranging elk. Products tested included filets, sausages, boneless steaks, burgers, ham steaks, seasoned chili meats, and spiced meats. CWD-prion presence in these products were assessed by PMCA using deer and elk substrates. Our results show positive prion detection in all products. To confirm the resilience of CWD-prions to traditional cooking methods, we grilled and boiled the meat products and evaluated them for any remnant PMCA seeding activity. Results confirmed the presence of CWD-prions in these meat products suggesting that infectious particles may still be available to people even after cooking. Our results strongly suggest ongoing human exposure to CWD-prions and raise significant concerns of zoonotic transmission through ingestion of CWD contaminated meat products.
***> Products tested included filets, sausages, boneless steaks, burgers, ham steaks, seasoned chili meats, and spiced meats.
***> CWD-prion presence in these products were assessed by PMCA using deer and elk substrates.
***> Our results show positive prion detection in all products.
***> Results confirmed the presence of CWD-prions in these meat products suggesting that infectious particles may still be available to people even after cooking.
***> Our results strongly suggest ongoing human exposure to CWD-prions and raise significant concerns of zoonotic transmission through ingestion of CWD contaminated meat products.
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9 Carrot plants as potential vectors for CWD transmission.
Paulina Soto1,2, Francisca Bravo-Risi1,2, Claudio Soto1, Rodrigo Morales1,2
1Department of Neurology, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, USA. 2Universidad Bernardo O’Higgins, Santiago, Chile
***> We show that edible plant components can absorb prions from CWD-contaminated soils and transport them to their aerial parts.
***> Our results indicate that edible plants could participate as vectors of CWD transmission
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Transmission of prion infectivity from CWD-infected macaque tissues to rodent models demonstrates the zoonotic potential of chronic wasting disease.
Samia Hannaoui1,2, Ginny Cheng1,2, Wiebke Wemheuer3, Walter Schulz-Schaeffer3, Sabine Gilch1,2, Hermann Schatzl1,2 1University of Calgary, Calgary, Canada. 2Calgary Prion Research Unit, Calgary, Canada. 3Institute of Neuropathology, Medical Faculty, Saarland University, Homburg/Saar, Germany
***> Further passage to cervidized mice revealed transmission with a 100% attack rate.
***> Our findings demonstrate that macaques, considered the best model for the zoonotic potential of prions, were infected upon CWD challenge, including the oral one.
****> The disease manifested as atypical in macaques and initial transgenic mouse transmissions, but with infectivity present at all times, as unveiled in the bank vole model with an unusual tissue tropism.
***> Epidemiologic surveillance of prion disease among cervid hunters and people likely to have consumed venison contaminated with chronic wasting disease
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intcwdsympo.files.wordpress.com/2023/06/final-agenda-with-abstracts.pdf?force_download=true
Transmission of Cervid Prions to Humanized Mice Demonstrates the Zoonotic Potential of CWD
Samia Hannaouia, Irina Zemlyankinaa, Sheng Chun Changa, Maria Immaculata Arifina, Vincent Béringueb, Debbie McKenziec, Hermann M. Schatzla, and Sabine Gilcha
Results: Here, we provide the strongest evidence supporting the zoonotic potential of CWD prions, and their possible phenotype in humans. Inoculation of mice expressing human PrPCwith deer CWD isolates (strains Wisc-1 and 116AG) resulted in atypical clinical manifestations in > 75% of the mice, with myoclonus as leading clinical sign. Most of tg650brain homogenates were positive for seeding activity in RT-QuIC. Clinical disease and presentation was transmissible to tg650 mice and bank voles. Intriguingly, protease-resistant PrP in the brain of tg650 mice resembled that found in a familial human prion disease and was transmissible upon passage. Abnormal PrP aggregates upon infection with Wisc-1 were detectable in thalamus, hypothalamus, and midbrain/pons regions.
Unprecedented in human prion disease, feces of CWD-inoculated tg650 mice harbored prion seeding activity and infectious prions, as shown by inoculation of bank voles and tg650 with fecal homogenates.
Conclusions: This is the first evidence that CWD can infect humans and cause disease with a distinctive clinical presentation, signature, and tropism, which might be transmissible between humans while current diagnostic assays might fail to detect it. These findings have major implications for public health and CWD-management.
www.tandfonline.com/doi/full/10.1080/19336896.2022.2091286 The finding that infectious PrPSc was shed in fecal material of CWD-infected humanized mice and induced clinical disease, different tropism, and typical three banding pattern-PrPres in bank voles that is transmissible upon second passage is highly concerning for public health. The fact that this biochemical signature in bank voles resembles that of the Wisc-1 original deer isolate and is different from that of bvWisc-1, in the migration profile and the glyco-form-ratio, is valid evidence that these results are not a product of contamination in our study. If CWD in humans is found to be contagious and transmissible among humans, as it is in cervids [57], the spread of the disease within humans might become endemic.
Transmission of cervid prions to humanized mice demonstrates the zoonotic potential of CWD
Acta Neuropathol 144, 767–784 (2022). doi.org/10.1007/s00401-022-02482-9
Published
22 August 2022
link.springer.com/article/10.1007/s00401-022-02482-9
Transmission of cervid prions to humanized mice demonstrates the zoonotic potential of CWD
Samia Hannaoui1 · Irina Zemlyankina1 · Sheng Chun Chang1 · Maria Immaculata Arifn1 · Vincent Béringue2 · Debbie McKenzie3 · Hermann M. Schatzl1 · Sabine Gilch1
Received: 24 May 2022 / Revised: 5 August 2022 / Accepted: 7 August 2022
© The Author(s) 2022
Abstract
Prions cause infectious and fatal neurodegenerative diseases in mammals. Chronic wasting disease (CWD), a prion disease of cervids, spreads efficiently among wild and farmed animals. Potential transmission to humans of CWD is a growing concern due to its increasing prevalence. Here, we provide evidence for a zoonotic potential of CWD prions, and its probable signature using mice expressing human prion protein (PrP) as an infection model. Inoculation of these mice with deer CWD isolates resulted in atypical clinical manifestation with prion seeding activity and efficient transmissible infectivity in the brain and, remarkably, in feces, but without classical neuropathological or Western blot appearances of prion diseases. Intriguingly, the protease-resistant PrP in the brain resembled that found in a familial human prion disease and was transmissible upon second passage. Our results suggest that CWD might infect humans, although the transmission barrier is likely higher compared to zoonotic transmission of cattle prions. Notably, our data suggest a different clinical presentation, prion signature, and tissue tropism, which causes challenges for detection by current diagnostic assays. Furthermore, the presence of infectious prions in feces is concerning because if this occurs in humans, it is a source for human-to-human transmission. These findings have strong implications for public health and CWD management.
Keywords Chronic wasting disease · CWD · Zoonotic potential · Prion strains · Zoonotic prions
HIGHLIGHTS OF THIS STUDY
================================
Our results suggest that CWD might infect humans, although the transmission barrier is likely higher compared to zoonotic transmission of cattle prions. Notably, our data suggest a different clinical presentation, prion signature, and tissue tropism, which causes challenges for detection by current diagnostic assays. Furthermore, the presence of infectious prions in feces is concerning because if this occurs in humans, it is a source for human-to-human transmission. These findings have strong implications for public health and CWD management.
In this study, we evaluated the zoonotic potential of CWD using a transgenic mouse model overexpressing human M129-PrPC (tg650 [12]). We inoculated tg650 mice intracerebrally with two deer CWD isolates, Wisc-1 and 116AG [22, 23, 27, 29]. We demonstrate that this transgenic line was susceptible to infection with CWD prions and displayed a distinct leading clinical sign, an atypical PrPSc signature and unusual fecal shedding of infectious prions. Importantly, these prions generated by the human PrP transgenic mice were transmissible upon passage. Our results are the first evidence of a zoonotic risk of CWD when using one of the most common CWD strains, Wisc-1/CWD1 for infection. We demonstrated in a human transgenic mouse model that the species barrier for transmission of CWD to humans is not absolute. The fact that its signature was not typical raises the questions whether CWD would manifest in humans as a subclinical infection, whether it would arise through direct or indirect transmission including an intermediate host, or a silent to uncovered human-to-human transmission, and whether current detection techniques will be suffcient to unveil its presence.
Our findings strongly suggest that CWD should be regarded as an actual public health risk. Here, we use humanized mice to show that CWD prions can cross the species barrier to humans, and remarkably, infectious prions can be excreted in feces.
Our results indicate that if CWD crosses the species-barrier to humans, it is unlikely to resemble the most common forms of human prion diseases with respect to clinical signs, tissue tropism and PrPSc signature. For instance, PrPSc in variable protease-sensitive prionopathy (VPSPr), a sporadic form of human prion disease, and in the genetic form Gerstmann-Sträussler-Scheinker syndrome (GSS) is defined by an atypical PK-resistant PrPSc fragment that is non-glycosylated and truncated at both C- and N-termini, with a molecular weight between 6 and 8 kDa [24, 44–46]. These biochemical features are unique and distinctive from PrPSc (PrP27-30) found in most other human or animal prion disease. The atypical PrPSc signature detected in brain homogenate of tg650 mice #321 (1st passage) and #3063 (2nd passage), and the 7–8 kDa fragment (Figs. 2, 4) are very similar to that of GSS, both in terms of migration profile and the N-terminal cleavage site.
CWD in humans might remain subclinical but with PrPSc deposits in the brain with an unusual morphology that does not resemble the patterns usually seen in different prion diseases (e.g., mouse #328; Fig. 3), clinical with untraceable abnormal PrP (e.g., mouse #327) but still transmissible and uncovered upon subsequent passage (e.g., mouse #3063; Fig. 4), or prions have other reservoirs than the usual ones, hence the presence of infectivity in feces (e.g., mouse #327) suggesting a potential for human-to-human transmission and a real iatrogenic risk that might be unrecognizable.
suggesting a potential for human-to-human transmission and a real iatrogenic risk that might be unrecognizable.
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Supplementary Information The online version contains supplementary material available at
doi.org/10.1007/s00401-022-02482-9
snip...see full text
link.springer.com/article/10.1007/s00401-022-02482-9
link.springer.com/content/pdf/10.1007/s00401-022-02482-9.pdf
Fortuitous generation of a zoonotic cervid prion strain
Manuel Camacho, Xu Qi, Liuting Qing, Sydney Smith, Jieji Hu, Wanyun Tao, Ignazio Cali, Qingzhong Kong. Department of Pathology, Case Western Reserve University, Cleveland, USA
Aims: Whether CWD prions can infect humans remains unclear despite the very substantial scale and long history of human exposure of CWD in many states or provinces of USA and Canada. Multiple in vitro conversion experiments and in vivo animal studies indicate that the CWD-to-human transmission barrier is not unbreakable. A major long-term public health concern on CWD zoonosis is the emergence of highly zoonotic CWD strains. We aim to address the question of whether highly zoonotic CWD strains are possible.
Materials and Methods: We inoculated several sCJD brain samples into cervidized transgenic mice (Tg12), which were intended as negative controls for bioassays of brain tissues from sCJD cases who had potentially been exposed to CWD. Some of the Tg12 mice became infected and their brain tissues were further examined by Western blot as well as serial passages in humanized or cervidized mice.
Results: Passage of sCJDMM1 in transgenic mice expressing elk PrP (Tg12) resulted in a “cervidized” CJD strain that we termed CJDElkPrP. We observed 100% transmission of the original CJDElkPrP in transgenic mice expressing human PrP. We passaged CJDElkPrP two more times in the Tg12 mice. We found that such second and third passage CJDElkPrP prions retained 100% transmission rate in the humanized mice, despite that the natural elk CWD isolates and CJDElkPrP share the same elk PrP sequence. In contrast, we and others found zero or poor transmission of natural elk CWD isolates in humanized mice.
Conclusions: Our data indicate that highly zoonotic cervid prion strains are not only possible but also can retain zoonotic potential after serial passages in cervids, suggesting a very significant and serious long-term risk of CWD zoonosis given that the broad and continuing spread of CWD prions will provide fertile grounds for the emergence of zoonotic CWD strains over time.
Funded by: NIH Grant number: R01NS052319, R01NS088604, R01NS109532
Acknowledgement: We want to thank the National Prion Disease Pathology Surveillance Center and Drs. Allen Jenny and Katherine O'Rourke for providing the sCJD samples and the CWD samples used in this study, respectively
"Our data indicate that highly zoonotic cervid prion strains are not only possible but also can retain zoonotic potential after serial passages in cervids, suggesting a very significant and serious long-term risk of CWD zoonosis given that the broad and continuing spread of CWD prions will provide fertile grounds for the emergence of zoonotic CWD strains over time."
PRION 2023 CONTINUED;
prion2023.org/wp-content/uploads/2023/10/Meeting-book-final-version2.pdf
A probable diagnostic marker for CWD infection in humans
Xu Qi, Liuting Qing, Manuel Camacho, Ignazio Cali, Qingzhong Kong. Department of Pathology, Case Western Reserve University, Cleveland, USA
Aims: Multiple in vitro CWD-seeded human PrP conversion experiments and some animal model studies indicate that the species barrier for CWD to human transmission can be overcome, but whether CWD prion can infect humans in real life remains controversial. The very limited understanding on the likely features of CWD infection in humans and the lack of a reliable diagnostic marker for identification of acquired human CWD cases contribute to this uncertainty. We aim to stablish such a reliable diagnostic marker for CWD infections in humans should they occur.
Materials and Methods: A couple of PrPSc-positive spleens were identified from humanized transgenic mice inoculated with either CWD or sCJDMM1. Prions in these spleens were compared by bioassays in cervidized or humanized transgenic mice. A couple of PrPSc-positive spleens from UK sCJDMM1 patients were also examined similarly as controls with no exposure to CWD.
Results: We have detected two prion-positive spleens in humanized transgenic mice inoculated with some CWD isolates. Such experimentally generated splenic “humanized” CWD prions (termed eHuCWDsp) appear indistinguishable from prions in the brain of sCJDMM1 patients on Western blot. We compared eHuCWDsp with prions in the spleen from humanized mice infected with sCJDMM1 (termed sCJDMM1sp) by bioassays in cervidized or humanized transgenic mice. Significantly, we found that eHuCWDsp can efficiently infect not only the humanized mice but also cervidized transgenic mice, and cervidized mice infected by eHuCWDsp produced PrPSc and brain pathology that are practically identical to those of CWD-infected cervidized mice. In contrast, sCJDMM1sp, similar to prions from sCJDMM1 patient brains, is poorly transmissible in the cervidized mice.
Conclusions: Our data demonstrate that high transmissibility with CWD features of splenic prions in cervidized transgenic mice is unique to acquired human CWD prions, and it may serve as a reliable marker to identify the first acquired human CWD cases.
Funded by: NIH Grant number: R01NS052319, R01NS088604, R01NS109532
Acknowledgement: We want to thank the National Prion Disease Pathology Surveillance Center and Drs. Allen Jenny and Katherine O'Rourke for providing the sCJD samples and the CWD samples used in this study, respectively.
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PRION 2023 CONTINUED;
prion2023.org/wp-content/uploads/2023/10/Meeting-book-final-version2.pdf
Prion 2023 Experimental Oronasal Inoculation of the Chronic Wasting Disease Agent into White Tailed Deer
Author list: Sarah Zurbuchena,b , S. Jo Moorea,b , Jifeng Biana , Eric D. Cassmanna , and Justin J. Greenleea . a. Virus and Prion Research Unit, National Animal Disease Center, ARS, United States Department of Agriculture, Ames, IA, US b. Oak Ridge Institute for Science and Education (ORISE), U.S. Department of Energy, Oak Ridge, TN, United States
Aims: The purpose of this experiment was to determine whether white-tailed deer (WTD) are susceptible to inoculation of chronic wasting disease (CWD) via oronasal exposure.
Materials and methods: Six male, neutered WTD were oronasally inoculated with brainstem material (10% w/v) from a CWD-positive wild-type WTD. The genotypes of five inoculated deer were Q95/G96 (wild-type). One inoculated deer was homozygous S at codon 96 (96SS). Cervidized (Tg12; M132 elk PrP) mice were inoculated with 1% w/v brainstem homogenate from either a 96GG WTD (n=10) or the 96SS WTD (n=10).
Results: All deer developed characteristic clinical signs of CWD including weight loss, regurgitation, and ataxia. The 96SS individual had a prolonged disease course and incubation period compared to the other deer. Western blots of the brainstem on all deer yielded similar molecular profiles. All deer had widespread lymphoid distribution of PrPCWD and neuropathologic lesions associated with transmissible spongiform encephalopathies. Both groups of mice had a 100% attack rate and developed clinical signs, including loss of body condition, ataxia, and loss of righting reflex. Mice inoculated with material from the 96SS deer had a significantly shorter incubation period than mice inoculated with material from 96GG deer (Welch two sample T-test, P<0.05). Serial dilutions of each inocula suggests that differences in incubation period were not due to a greater concentration of PrPCWD in the 96SS inoculum. Molecular profiles from western blot of brain homogenates from mice appeared similar regardless of inoculum and appear similar to those of deer used for inoculum.
Conclusions: This study characterizes the lesions and clinical course of CWD in WTD inoculated in a similar manner to natural conditions. It supports previous findings that 96SS deer have a prolonged disease course. Further, it describes a first pass of inoculum from a 96SS deer in cervidized mice which shortened the incubation period.
Funded by: This research was funded in its entirety by congressionally appropriated funds to the United States Department of Agriculture, Agricultural Research Service. The funders of the work did not influence study design, data collection, analysis, decision to publish, or preparation of the manuscript.
Acknowledgement: We thank Ami Frank and Kevin Hassall for their technical contributions to this project.
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PRION 2023 CONTINUED;
prion2023.org/wp-content/uploads/2023/10/Meeting-book-final-version2.pdf
The detection and decontamination of chronic wasting disease prions during venison processing
Marissa S. Milstein1,2, Marc D. Schwabenlander1,2, Sarah C. Gresch1,2, Manci Li1,2, Stuart Lichtenberg1,2, Rachel Shoemaker1,2, Gage R. Rowden1,2, Jason C. Bartz2,3 , Tiffany M. Wolf2,4, Peter A. Larsen1,2
Presenting author: Tiffany M. Wolf 1 Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, St. Paul, Minnesota, USA 2 Minnesota Center for Prion Research and Outreach, College of Veterinary Medicine, University of Minnesota, St. Paul, Minnesota, USA 3 Department of Medical Microbiology and Immunology, School of Medicine, Creighton University, Omaha, Nebraska, USA 4 Department of Veterinary Population Medicine, College of Veterinary Medicine, University of Minnesota, St. Paul, Minnesota, USA
Aims: There is a growing concern that chronic wasting disease (CWD) prions in venison pose a risk to human health. CWD prions accumulate in infected deer tissues that commonly enter the human food chain through meat processing and consumption. The United States (US) Food and Drug Administration and US Department of Agriculture now formally consider CWD-positive venison unfit for human and animal consumption. Yet, the degree to which prion contamination occurs during routine venison processing is unknown. Here, we use environmental surface swab methods to: a) experimentally test meat processing equipment (i.e., stainless steel knives and polyethylene cutting boards) before and after processing CWD-positive venison and b) test the efficacy of five different disinfectant types (i.e., Dawn dish soap, Virkon-S, Briotech, 10% bleach, and 40% bleach) to determine prion decontamination efficacy.
Materials and Methods: We used a real-time quaking-induced conversion (RT-QuIC) assay to determine CWD infection status of venison and to detect CWD prions in the swabs. We collected three swabs per surface and ran eight technical replicates on RT-QuIC.
Results: CWD prions were detected on all cutting boards (n= 3; replicates= 8/8, 8/8, 8/8 and knives (n= 3; replicates= 8/8, 8/8, 8/8) used in processing CWD-positive venison, but not on those used for CWD-negative venison. After processing CWD-positive venison, allowing the surfaces to dry, and washing the cutting board with Dawn dish soap, we detected CWD prions on the cutting board surface (n= 3; replicates= 8/8, 8/8, 8/8) but not on the knife (n= 3, replicates = 0/8, 0/8, 0/8). Similar patterns were observed with Briotech (cutting board: n= 3; replicates= 7/8, 1/8, 0/8; knife: n= 3; replicates = 0/8, 0/8, 0/8). We did not detect CWD prions on the knives or cutting boards after disinfecting with Virkon-S, 10% bleach, and 40% bleach.
Conclusions: These preliminary results suggest that Dawn dish soap and Briotech do not reliably decontaminate CWD prions from these surfaces. Our data suggest that Virkon-S and various bleach concentrations are more effective in reducing prion contamination of meat processing surfaces; however, surface type may also influence the ability of prions to adsorb to surfaces, preventing complete decontamination. Our results will directly inform best practices to prevent the introduction of CWD prions into the human food chain during venison processing.
Acknowledgement: Funding was provided by the Minnesota Environment and Natural Resources Trust Fund as recommended by the Legislative-Citizen Commission on Minnesota Resources (LCCMR), the Rapid Agriculture Response Fund (#95385/RR257), and the Michigan Department of Natural Resources.
Theme: Animal prion diseases
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Prion 2023 Abstracts
prion2023.org/wp-content/uploads/2023/10/Meeting-book-final-version2.pdf
8. Even though human TSE‐exposure risk through consumption of game from European cervids can be assumed to be minor, if at all existing, no final conclusion can be drawn due to the overall lack of scientific data.
***> In particular the US data do not clearly exclude the possibility of human (sporadic or familial) TSE development due to consumption of venison.
The Working Group thus recognizes a potential risk to consumers if a TSE would be present in European cervids. It might be prudent considering appropriate measures to reduce such a risk, e.g. excluding tissues such as CNS and lymphoid tissues from the human food chain, which would greatly reduce any potential risk for consumers.. However, it is stressed that currently, no data regarding a risk of TSE infections from cervid products are available.
efsa.onlinelibrary.wiley.com/doi/full/10.2903/j.efsa.2018.5132
Research Paper
Cellular prion protein distribution in the vomeronasal organ, parotid, and scent glands of white-tailed deer and mule deer
Anthony Ness, Aradhana Jacob, Kelsey Saboraki, Alicia Otero, Danielle Gushue, Diana Martinez Moreno, Melanie de Peña, Xinli Tang, Judd Aiken, Susan Lingle & Debbie McKenzieORCID Icon show less
Pages 40-57 | Received 03 Feb 2022, Accepted 13 May 2022, Published online: 29 May 2022
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doi.org/10.1080/19336896.2022.2079888
ABSTRACT
Chronic wasting disease (CWD) is a contagious and fatal transmissible spongiform encephalopathy affecting species of the cervidae family. CWD has an expanding geographic range and complex, poorly understood transmission mechanics. CWD is disproportionately prevalent in wild male mule deer and male white-tailed deer. Sex and species influences on CWD prevalence have been hypothesized to be related to animal behaviours that involve deer facial and body exocrine glands. Understanding CWD transmission potential requires a foundational knowledge of the cellular prion protein (PrPC) in glands associated with cervid behaviours. In this study, we characterized the presence and distribution of PrPC in six integumentary and two non-integumentary tissues of hunter-harvested mule deer (Odocoileus hemionus) and white-tailed deer (O. virginianus). We report that white-tailed deer expressed significantly more PrPC than their mule deer in the parotid, metatarsal, and interdigital glands. Females expressed more PrPC than males in the forehead and preorbital glands. The distribution of PrPC within the integumentary exocrine glands of the face and legs were localized to glandular cells, hair follicles, epidermis, and immune cell infiltrates. All tissues examined expressed sufficient quantities of PrPC to serve as possible sites of prion initial infection, propagation, and shedding.
www.tandfonline.com/doi/full/10.1080/19336896.2022.2079888
ARS RESEARCH Generation of human chronic wasting disease in transgenic mice
Publication Acceptance Date: 9/8/2021
Research Project: Pathobiology, Genetics, and Detection of Transmissible Spongiform Encephalopathies Location: Virus and Prion Research
Title: Generation of human chronic wasting disease in transgenic mice
Author item WANG, ZERUI - Case Western Reserve University (CWRU) item QIN, KEFENG - University Of Chicago item CAMACHO, MANUEL - Case Western Reserve University (CWRU) item SHEN, PINGPING - Case Western Reserve University (CWRU) item YUAN, JUE - Case Western Reserve University (CWRU) item Greenlee, Justin item CUI, LI - Jilin University item KONG, QINGZHONG - Case Western Reserve University (CWRU) item MASTRIANNI, JAMES - University Of Chicago item ZOU, WEN-QUAN - Case Western Reserve University (CWRU)
Submitted to: Acta Neuropathologica Publication Type: Peer Reviewed Journal Publication Acceptance Date: 9/8/2021 Publication Date: N/A Citation: N/A
Interpretive Summary: Prion diseases are invariably fatal neurologic diseases for which there is no known prevention or cure. Chronic wasting disease (CWD) is the prion disease of deer and elk and is present in farmed and free ranging herds throughout North America. To date there is no clear evidence that the CWD agent could be transmitted to humans. This manuscript describes the use of an in vitro technique, cell-free serial protein misfolding cyclic amplification (sPMCA), to generate a CWD prion that is infectious to transgenic mice expressing the human prion protein. This study provides the first evidence that CWD prions may be able to cause misfolding in the human prion protein. This information will impact medical experts and those involved in making policy for farmed cervids and wildlife.
Technical Abstract: Chronic wasting disease (CWD) is a cervid spongiform encephalopathy or prion disease caused by the infectious prion or PrPSc, a misfolded conformer of cellular prion protein (PrPC). It has rapidly spread in North America and also has been found in Asia and Europe. In contrast to the zoonotic mad cow disease that is the first animal prion disease found transmissible to humans, the transmissibility of CWD to humans remains uncertain although most previous studies have suggested that humans may not be susceptible to CWD. Here we report the generation of an infectious human PrPSc by seeding CWD PrPSc in normal human brain PrPC through the in vitro cell-free serial protein misfolding cyclic amplification (sPMCA). Western blotting confirms that the sPMCA-induced proteinase K-resistant PrPSc is a human form, evidenced by a PrP-specific antibody that recognizes human but not cervid PrP. Remarkably, two lines of humanized transgenic (Tg) mice expressing human PrP-129Val/Val (VV) or -129Met/Met (MM) polymorphism develop prion disease at 233 ± 6 (mean ± SE) days post-inoculation (dpi) and 552 ± 27 dpi, respectively, upon intracerebral inoculation with the sPMCA-generated PrPSc. The brain of diseased Tg mice reveals the electrophoretic profile of PrPSc similar to sporadic Creutzfeldt-Jakob disease (sCJD) MM1 or VV2 subtype but different neuropathological patterns. We believe that our study provides the first evidence that CWD PrPSc is able to convert human PrPC into PrPSc in vitro and the CWD-derived human PrPSc mimics atypical sCJD subtypes in humanized Tg mice.
www.ars.usda.gov/research/publications/publication/?seqNo115=382551
''The brain of diseased Tg mice reveals the electrophoretic profile of PrPSc similar to sporadic Creutzfeldt-Jakob disease (sCJD) MM1 or VV2 subtype but different neuropathological patterns.''
''We believe that our study provides the first evidence that CWD PrPSc is able to convert human PrPC into PrPSc in vitro and the CWD-derived human PrPSc mimics atypical sCJD subtypes in humanized Tg mice.''
Published: 26 September 2021
Generation of human chronic wasting disease in transgenic mice
Zerui Wang, Kefeng Qin, Manuel V. Camacho, Ignazio Cali, Jue Yuan, Pingping Shen, Justin Greenlee, Qingzhong Kong, James A. Mastrianni & Wen-Quan Zou
Acta Neuropathologica Communications volume 9, Article number: 158 (2021)
Abstract
Chronic wasting disease (CWD) is a cervid prion disease caused by the accumulation of an infectious misfolded conformer (PrPSc) of cellular prion protein (PrPC). It has been spreading rapidly in North America and also found in Asia and Europe. Although bovine spongiform encephalopathy (i.e. mad cow disease) is the only animal prion disease known to be zoonotic, the transmissibility of CWD to humans remains uncertain. Here we report the generation of the first CWD-derived infectious human PrPSc by elk CWD PrPSc-seeded conversion of PrPC in normal human brain homogenates using in vitro protein misfolding cyclic amplification (PMCA). Western blotting with human PrP selective antibody confirmed that the PMCA-generated protease-resistant PrPSc was derived from the human PrPC substrate. Two lines of humanized transgenic mice expressing human PrP with either Val or Met at the polymorphic codon 129 developed clinical prion disease following intracerebral inoculation with the PMCA-generated CWD-derived human PrPSc. Diseased mice exhibited distinct PrPSc patterns and neuropathological changes in the brain. Our study, using PMCA and animal bioassays, provides the first evidence that CWD PrPSc can cross the species barrier to convert human PrPC into infectious PrPSc that can produce bona fide prion disease when inoculated into humanized transgenic mice.
Snip...
It is worth noting that the annual number of sporadic CJD (sCJD) cases in the USA has increased, with the total number of suspected and confirmed sCJD cases rising from 284 in 2003 to 511 in 2017 (https://www.cdc.gov/prions/cjd/occurrence-transmission.html). The greatly enhanced CJD surveillance and an aging population in the USA certainly contributed to the observed increase in annual sCJD case numbers in recent years, but the possibility cannot be excluded that some of the increased sCJD prevalence is linked to CWD exposure.
In the present study, using serial protein misfolding cyclic amplification (sPMCA) assay we generate PrPSc by seeding CWD prions in normal human brain homogenates. Importantly, we reveal that two lines of humanized Tg mice expressing human PrP-129VV and 129MM develop prion diseases upon intracerebral inoculation of the abnormal PrP generated by sPMCA. We believe that our study provides the first opportunity to dissect the clinical, pathological and biochemical features of the CWD-derived human prion disease in two lines of humanized Tg mice expressing two major human PrP genotypes, respectively.
actaneurocomms.biomedcentral.com/articles/10.1186/s40478-021-01262-y
i thought i might share some news about cwd zoonosis that i got, that i cannot share or post to the public yet, i promised for various reasons, one that it will cause a shit storm for sure, but it was something i really already knew from previous studies, but, i was told that ;
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''As you can imagine, 2 and 5 (especially 5) may raise alarms. The evidence we have for 4 are not as strong or tight as I would like to have. At this point, please do not post any of the points publicly yet, but you can refer to points 1-3 in private discussions and all 5 points when discussing with relevant public officials to highlight the long-term risks of CWD zoonosis.''
====================
so, i figure your as about as official as it gets, and i think this science is extremely important for you to know and to converse about with your officials. it's about to burn a whole in my pocket. this is about as close as it will ever get for cwd zoonosis to be proven in my time, this and what Canada Czub et al found with the Macaques, plus an old study from cjd surveillance unit back that showed cjd and a 9% increase in risk from folks that eat venison, i will post all this below for your files Sir. i remember back in the BSE nvCJD days, from when the first BSE case in bovine was confirmed around 1984 maybe 83, i forget the good vets named that screwed it up first, Carol something, but from 83ish to 95 96 when nvCJD was linked to humans from BSE in cattle, so that took 10 to 15 years. hell, at that rate, especially with Texas and cwd zoonsis, hell, i'll be dead before it's official, if ever, so here ya go Sir. there was a grant study on cwd zoonosis that had been going on for some time, i followed it over the years, then the grant date for said study had expired, so, i thought i would write the good Professor about said study i.e. Professor Kong, CWRU et al. i will post the grant study abstract first, and then after that, what reply i got back, about said study that i was told not to post/publish...
CWD ZOONOSIS GRANT FIRST;
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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
snip...
grantome.com/grant/NIH/R01-NS088604-01A1#panel-abstract
Professor Kongs reply to me just this month about above grant study that has NOT been published in peer reveiw yet...
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Here is a brief summary of our findings:
snip...can't post, made a promise...tss
On Sat, Apr 3, 2021 at 12:19 PM Terry Singeltary <flounder9@verizon.net> wrote:
snip...
end...tss
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CWD ZOONOSIS THE FULL MONTY TO DATE
International Conference on Emerging Diseases, Outbreaks & Case Studies & 16th Annual Meeting on Influenza March 28-29, 2018 | Orlando, USA
Qingzhong Kong
Case Western Reserve University School of Medicine, USA
Zoonotic potential of chronic wasting disease prions from cervids
Chronic wasting disease (CWD) is the prion disease in cervids (mule deer, white-tailed deer, American elk, moose, and reindeer). It has become an epidemic in North America, and it has been detected in the Europe (Norway) since 2016. The widespread CWD and popular hunting and consumption of cervid meat and other products raise serious public health concerns, but questions remain on human susceptibility to CWD prions, especially on the potential difference in zoonotic potential among the various CWD prion strains. We have been working to address this critical question for well over a decade. We used CWD samples from various cervid species to inoculate transgenic mice expressing human or elk prion protein (PrP). We found infectious prions in the spleen or brain in a small fraction of CWD-inoculated transgenic mice expressing human PrP, indicating that humans are not completely resistant to CWD prions; this finding has significant ramifications on the public health impact of CWD prions. The influence of cervid PrP polymorphisms, the prion strain dependence of CWD-to-human transmission barrier, and the characterization of experimental human CWD prions will be discussed.
Speaker Biography Qingzhong Kong has completed his PhD from the University of Massachusetts at Amherst and Post-doctoral studies at Yale University. He is currently an Associate Professor of Pathology, Neurology and Regenerative Medicine. He has published over 50 original research papers in reputable journals (including Science Translational Medicine, JCI, PNAS and Cell Reports) and has been serving as an Editorial Board Member on seven scientific journals. He has multiple research interests, including public health risks of animal prions (CWD of cervids and atypical BSE of cattle), animal modeling of human prion diseases, mechanisms of prion replication and pathogenesis, etiology of sporadic Creutzfeldt-Jacob disease (CJD) in humans, normal cellular PrP in the biology and pathology of multiple brain and peripheral diseases, proteins responsible for the α-cleavage of cellular PrP, as well as gene therapy and DNA vaccination.
qxk2@case.edu
www.alliedacademies.org/conference-abstracts-files/zoonotic-potential-of-chronic-wasting-disease-prions-from.pdf
prionconference.blogspot.com/2018/02/prion-round-table-conference-2018-may.html
prionconference.blogspot.com/
SUNDAY, JULY 25, 2021
North American and Norwegian Chronic Wasting Disease prions exhibit different potential for interspecies transmission and zoonotic risk
''Our data suggest that reindeer and red deer from Norway could be the most transmissible CWD prions to other mammals, whereas North American CWD prions were more prone to generate human prions in vitro.''
chronic-wasting-disease.blogspot.com/2021/07/north-american-and-norwegian-chronic.html
MONDAY, JULY 19, 2021
***> U Calgary researchers at work on a vaccine against a fatal infectious disease affecting deer and potentially people
chronic-wasting-disease.blogspot.com/2021/07/u-calgary-researchers-at-work-on.html
Prion Conference 2018 Abstracts
BSE aka MAD COW DISEASE, was first discovered in 1984, and it took until 1995 to finally admit that BSE was causing nvCJD, the rest there is history, but that science is still evolving i.e. science now shows that indeed atypical L-type BSE, atypical Nor-98 Scrapie, and typical Scrapie are all zoonosis, zoonotic for humans, there from.
HOW long are we going to wait for Chronic Wasting Disease, CWD TSE Prion of Cervid, and zoonosis, zoonotic transmission to humans there from?
Studies have shown since 1994 that humans are susceptible to CWD TSE Prion, so, what's the hold up with making CWD a zoonotic zoonosis disease, the iatrogenic transmissions there from is not waiting for someone to make a decision.
Prion Conference 2018 Abstracts
P190 Human prion disease mortality rates by occurrence of chronic wasting disease in free ranging cervids, United States
Abrams JY (1), Maddox RA (1), Schonberger LB (1), Person MK (1), Appleby BS (2), Belay ED (1)
(1) Centers for Disease Control and Prevention (CDC), National Center for Emerging and Zoonotic Infectious Diseases, Atlanta, GA, USA (2) Case Western Reserve University, National Prion Disease Pathology Surveillance Center (NPDPSC), Cleveland, OH, USA.
Background
Chronic wasting disease (CWD) is a prion disease of deer and elk that has been identified in free ranging cervids in 23 US states. While there is currently no epidemiological evidence for zoonotic transmission through the consumption of contaminated venison, studies suggest the CWD agent can cross the species barrier in experimental models designed to closely mimic humans. We compared rates of human prion disease in states with and without CWD to examine the possibility of undetermined zoonotic transmission.
Methods
Death records from the National Center for Health Statistics, case records from the National Prion Disease Pathology Surveillance Center, and additional state case reports were combined to create a database of human prion disease cases from 2003-2015. Identification of CWD in each state was determined through reports of positive CWD tests by state wildlife agencies. Age- and race-adjusted mortality rates for human prion disease, excluding cases with known etiology, were determined for four categories of states based on CWD occurrence: highly endemic (>16 counties with CWD identified in free-ranging cervids); moderately endemic (3-10 counties with CWD); low endemic (1-2 counties with CWD); and no CWD states. States were counted as having no CWD until the year CWD was first identified. Analyses stratified by age, sex, and time period were also conducted to focus on subgroups for which zoonotic transmission would be more likely to be detected: cases <55 years old, male sex, and the latter half of the study (2010-2015).
Results
Highly endemic states had a higher rate of prion disease mortality compared to non-CWD states (rate ratio [RR]: 1.12, 95% confidence interval [CI] = 1.01 - 1.23), as did low endemic states (RR: 1.15, 95% CI = 1.04 - 1.27). Moderately endemic states did not have an elevated mortality rate (RR: 1.05, 95% CI = 0.93 - 1.17). In age-stratified analyses, prion disease mortality rates among the <55 year old population were elevated for moderately endemic states (RR: 1.57, 95% CI = 1.10 – 2.24) while mortality rates were elevated among those ≥55 for highly endemic states (RR: 1.13, 95% CI = 1.02 - 1.26) and low endemic states (RR: 1.16, 95% CI = 1.04 - 1.29). In other stratified analyses, prion disease mortality rates for males were only elevated for low endemic states (RR: 1.27, 95% CI = 1.10 - 1.48), and none of the categories of CWD-endemic states had elevated mortality rates for the latter time period (2010-2015).
Conclusions
While higher prion disease mortality rates in certain categories of states with CWD in free-ranging cervids were noted, additional stratified analyses did not reveal markedly elevated rates for potentially sensitive subgroups that would be suggestive of zoonotic transmission. Unknown confounding factors or other biases may explain state-by-state differences in prion disease mortality.
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P172 Peripheral Neuropathy in Patients with Prion Disease
Wang H(1), Cohen M(1), Appleby BS(1,2)
(1) University Hospitals Cleveland Medical Center, Cleveland, Ohio (2) National Prion Disease Pathology Surveillance Center, Cleveland, Ohio.
Prion disease is a fatal progressive neurodegenerative disease due to deposition of an abnormal protease-resistant isoform of prion protein. Typical symptoms include rapidly progressive dementia, myoclonus, visual disturbance and hallucinations. Interestingly, in patients with prion disease, the abnormal protein canould also be found in the peripheral nervous system. Case reports of prion deposition in peripheral nerves have been reported. Peripheral nerve involvement is thought to be uncommon; however, little is known about the exact prevalence and features of peripheral neuropathy in patients with prion disease.
We reviewed autopsy-proven prion cases from the National Prion Disease Pathology Surveillance Center that were diagnosed between September 2016 to March 2017. We collected information regarding prion protein diagnosis, demographics, comorbidities, clinical symptoms, physical exam, neuropathology, molecular subtype, genetics lab, brain MRI, image and EMG reports. Our study included 104 patients. Thirteen (12.5%) patients had either subjective symptoms or objective signs of peripheral neuropathy. Among these 13 patients, 3 had other known potential etiologies of peripheral neuropathy such as vitamin B12 deficiency or prior chemotherapy. Among 10 patients that had no other clear etiology, 3 (30%) had familial CJD. The most common sCJD subtype was MV1-2 (30%), followed by MM1-2 (20%). The Majority of cases wasere male (60%). Half of them had exposure to wild game. The most common subjective symptoms were tingling and/or numbness of distal extremities. The most common objective finding was diminished vibratory sensation in the feet. Half of them had an EMG with the findings ranging from fasciculations to axonal polyneuropathy or demyelinating polyneuropathy.
Our study provides an overview of the pattern of peripheral neuropathy in patients with prion disease. Among patients with peripheral neuropathy symptoms or signs, majority has polyneuropathy. It is important to document the baseline frequency of peripheral neuropathy in prion diseases as these symptoms may become important when conducting surveillance for potential novel zoonotic prion diseases.
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P177 PrP plaques in methionine homozygous Creutzfeldt-Jakob disease patients as a potential marker of iatrogenic transmission
Abrams JY (1), Schonberger LB (1), Cali I (2), Cohen Y (2), Blevins JE (2), Maddox RA (1), Belay ED (1), Appleby BS (2), Cohen ML (2)
(1) Centers for Disease Control and Prevention (CDC), National Center for Emerging and Zoonotic Infectious Diseases, Atlanta, GA, USA (2) Case Western Reserve University, National Prion Disease Pathology Surveillance Center (NPDPSC), Cleveland, OH, USA.
Background
Sporadic Creutzfeldt-Jakob disease (CJD) is widely believed to originate from de novo spontaneous conversion of normal prion protein (PrP) to its pathogenic form, but concern remains that some reported sporadic CJD cases may actually be caused by disease transmission via iatrogenic processes. For cases with methionine homozygosity (CJD-MM) at codon 129 of the PRNP gene, recent research has pointed to plaque-like PrP deposition as a potential marker of iatrogenic transmission for a subset of cases. This phenotype is theorized to originate from specific iatrogenic source CJD types that comprise roughly a quarter of known CJD cases.
Methods
We reviewed scientific literature for studies which described PrP plaques among CJD patients with known epidemiological links to iatrogenic transmission (receipt of cadaveric human grown hormone or dura mater), as well as in cases of reported sporadic CJD. The presence and description of plaques, along with CJD classification type and other contextual factors, were used to summarize the current evidence regarding plaques as a potential marker of iatrogenic transmission. In addition, 523 cases of reported sporadic CJD cases in the US from January 2013 through September 2017 were assessed for presence of PrP plaques.
Results
We identified four studies describing 52 total cases of CJD-MM among either dura mater recipients or growth hormone recipients, of which 30 were identified as having PrP plaques. While sporadic cases were not generally described as having plaques, we did identify case reports which described plaques among sporadic MM2 cases as well as case reports of plaques exclusively in white matter among sporadic MM1 cases. Among the 523 reported sporadic CJD cases, 0 of 366 MM1 cases had plaques, 2 of 48 MM2 cases had kuru plaques, and 4 of 109 MM1+2 cases had either kuru plaques or both kuru and florid plaques. Medical chart review of the six reported sporadic CJD cases with plaques did not reveal clinical histories suggestive of potential iatrogenic transmission.
Conclusions
PrP plaques occur much more frequently for iatrogenic CJD-MM cases compared to sporadic CJDMM cases. Plaques may indicate iatrogenic transmission for CJD-MM cases without a type 2 Western blot fragment. The study results suggest the absence of significant misclassifications of iatrogenic CJD as sporadic. To our knowledge, this study is the first to describe grey matter kuru plaques in apparently sporadic CJD-MM patients with a type 2 Western blot fragment.
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P180 Clinico-pathological analysis of human prion diseases in a brain bank series
Ximelis T (1), Aldecoa I (1,2), Molina-Porcel L (1,3), Grau-Rivera O (4), Ferrer I (5), Nos C (6), Gelpi E (1,7), Sánchez-Valle R (1,4)
(1) Neurological Tissue Bank of the Biobanc-Hospital ClÃnic-IDIBAPS, Barcelona, Spain (2) Pathological Service of Hospital ClÃnic de Barcelona, Barcelona, Spain (3) EAIA Trastorns Cognitius, Centre Emili Mira, Parc de Salut Mar, Barcelona, Spain (4) Department of Neurology of Hospital ClÃnic de Barcelona, Barcelona, Spain (5) Institute of Neuropathology, Hospital Universitari de Bellvitge, Hospitalet de Llobregat, Barcelona (6) General subdirectorate of Surveillance and Response to Emergencies in Public Health, Department of Public Health in Catalonia, Barcelona, Spain (7) Institute of Neurology, Medical University of Vienna, Vienna, Austria.
Background and objective:
The Neurological Tissue Bank (NTB) of the Hospital Clínic-Institut d‘Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain is the reference center in Catalonia for the neuropathological study of prion diseases in the region since 2001. The aim of this study is to analyse the characteristics of the confirmed prion diseases registered at the NTB during the last 15 years.
Methods:
We reviewed retrospectively all neuropathologically confirmed cases registered during the period January 2001 to December 2016.
Results:
176 cases (54,3% female, mean age: 67,5 years and age range: 25-86 years) of neuropathological confirmed prion diseases have been studied at the NTB. 152 cases corresponded to sporadic Creutzfeldt-Jakob disease (sCJD), 10 to genetic CJD, 10 to Fatal Familial Insomnia, 2 to GerstmannSträussler-Scheinker disease, and 2 cases to variably protease-sensitive prionopathy (VPSPr). Within sCJD subtypes the MM1 subtype was the most frequent, followed by the VV2 histotype.
Clinical and neuropathological diagnoses agreed in 166 cases (94%). The clinical diagnosis was not accurate in 10 patients with definite prion disease: 1 had a clinical diagnosis of Fronto-temporal dementia (FTD), 1 Niemann-Pick‘s disease, 1 Lewy Body‘s Disease, 2 Alzheimer‘s disease, 1 Cortico-basal syndrome and 2 undetermined dementia. Among patients with VPSPr, 1 had a clinical diagnosis of Amyotrophic lateral sclerosis (ALS) and the other one with FTD.
Concomitant pathologies are frequent in older age groups, mainly AD neuropathological changes were observed in these subjects.
Discussion:
A wide spectrum of human prion diseases have been identified in the NTB being the relative frequencies and main characteristics like other published series. There is a high rate of agreement between clinical and neuropathological diagnoses with prion diseases. These findings show the importance that public health has given to prion diseases during the past 15 years. Continuous surveillance of human prion disease allows identification of new emerging phenotypes. Brain tissue samples from these donors are available to the scientific community. For more information please visit:
www.clinicbiobanc.org/banc-teixits-neurologics/mostres/en_index.html
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P192 Prion amplification techniques for the rapid evaluation of surface decontamination procedures
Bruyere-Ostells L (1), Mayran C (1), Belondrade M (1), Boublik Y (2), Haïk S (3), Fournier-Wirth C (1), Nicot S (1), Bougard D (1)
(1) Pathogenesis and control of chronic infections, Etablissement Français du Sang, Inserm, Université de Montpellier, Montpellier, France. (2) Centre de Recherche en Biologie cellulaire de Montpellier, CNRS, Université de Montpellier, Montpellier, France. (3) Inserm U 1127, CNRS UMR 7225, Sorbonne Universités, UPMC Université Paris 06 UMR S 1127, Institut du Cerveau et de la Moelle épinière, ICM, Paris, France.
Aims:
Transmissible Spongiform Encephalopathies (TSE) or prion diseases are a group of incurable and always fatal neurodegenerative disorders including Creutzfeldt-Jakob diseases (CJD) in humans. These pathologies include sporadic (sCJD), genetic and acquired (variant CJD) forms. By the past, sCJD and vCJD were transmitted by different prion contaminated biological materials to patients resulting in more than 400 iatrogenic cases (iCJD). The atypical nature and the biochemical properties of the infectious agent, formed by abnormal prion protein or PrPTSE, make it particularly resistant to conventional decontamination procedures. In addition, PrPTSE is widely distributed throughout the organism before clinical onset in vCJD and can also be detected in some peripheral tissues in sporadic CJD. Risk of iatrogenic transmission of CJD by contaminated medical device remains thus a concern for healthcare facilities. Bioassay is the gold standard method to evaluate the efficacy of prion decontamination procedures but is time-consuming and expensive. Here, we propose to compare in vitro prion amplification techniques: Protein Misfolding Cyclic Amplification (PMCA) and Real-Time Quaking Induced Conversion (RT-QuIC) for the detection of residual prions on surface after decontamination.
Methods:
Stainless steel wires, by mimicking the surface of surgical instruments, were proposed as a carrier model of prions for inactivation studies. To determine the sensitivity of the two amplification techniques on wires (Surf-PMCA and Surf-QuIC), steel wires were therefore contaminated with serial dilutions of brain homogenates (BH) from a 263k infected hamster and from a patient with sCJD (MM1 subtype). We then compared the different standard decontamination procedures including partially and fully efficient treatments by detecting the residual seeding activity on 263K and sCJD contaminated wires. We completed our study by the evaluation of marketed reagents endorsed for prion decontamination.
Results:
The two amplification techniques can detect minute quantities of PrPTSE adsorbed onto a single wire. 8/8 wires contaminated with a 10-6 dilution of 263k BH and 1/6 with the 10-8 dilution are positive with Surf-PMCA. Similar performances were obtained with Surf-QuIC on 263K: 10/16 wires contaminated with 10-6 dilution and 1/8 wires contaminated with 10-8 dilution are positive. Regarding the human sCJD-MM1 prion, Surf-QuIC allows us to detect 16/16 wires contaminated with 10-6 dilutions and 14/16 with 10-7 . Results obtained after decontamination treatments are very similar between 263K and sCJD prions. Efficiency of marketed treatments to remove prions is lower than expected.
Conclusions:
Surf-PMCA and Surf-QuIC are very sensitive methods for the detection of prions on wires and could be applied to prion decontamination studies for rapid evaluation of new treatments. Sodium hypochlorite is the only product to efficiently remove seeding activity of both 263K and sCJD prions.
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WA2 Oral transmission of CWD into Cynomolgus macaques: signs of atypical disease, prion conversion and infectivity in macaques and bio-assayed transgenic mice
Schatzl HM (1, 2), Hannaoui S (1, 2), Cheng Y-C (1, 2), Gilch S (1, 2), Beekes M (3), SchulzSchaeffer W (4), Stahl-Hennig C (5) and Czub S (2, 6)
(1) University of Calgary, Calgary Prion Research Unit, Calgary, Canada (2) University of Calgary, Faculty of Veterinary Medicine, Calgary, Canada, (3) Robert Koch Institute, Berlin, Germany, (4) University of Homburg/Saar, Homburg, Germany, (5) German Primate Center, Goettingen, Germany, (6) Canadian Food Inspection Agency (CFIA), Lethbridge, Canada.
To date, BSE is the only example of interspecies transmission of an animal prion disease into humans. The potential zoonotic transmission of CWD is an alarming issue and was addressed by many groups using a variety of in vitro and in vivo experimental systems. Evidence from these studies indicated a substantial, if not absolute, species barrier, aligning with the absence of epidemiological evidence suggesting transmission into humans. Studies in non-human primates were not conclusive so far, with oral transmission into new-world monkeys and no transmission into old-world monkeys. Our consortium has challenged 18 Cynomolgus macaques with characterized CWD material, focusing on oral transmission with muscle tissue. Some macaques have orally received a total of 5 kg of muscle material over a period of 2 years. After 5-7 years of incubation time some animals showed clinical symptoms indicative of prion disease, and prion neuropathology and PrPSc deposition were found in spinal cord and brain of euthanized animals. PrPSc in immunoblot was weakly detected in some spinal cord materials and various tissues tested positive in RT-QuIC, including lymph node and spleen homogenates. To prove prion infectivity in the macaque tissues, we have intracerebrally inoculated 2 lines of transgenic mice, expressing either elk or human PrP. At least 3 TgElk mice, receiving tissues from 2 different macaques, showed clinical signs of a progressive prion disease and brains were positive in immunoblot and RT-QuIC. Tissues (brain, spinal cord and spleen) from these and preclinical mice are currently tested using various read-outs and by second passage in mice. Transgenic mice expressing human PrP were so far negative for clear clinical prion disease (some mice >300 days p.i.). In parallel, the same macaque materials are inoculated into bank voles. Taken together, there is strong evidence of transmissibility of CWD orally into macaques and from macaque tissues into transgenic mouse models, although with an incomplete attack rate. The clinical and pathological presentation in macaques was mostly atypical, with a strong emphasis on spinal cord pathology. Our ongoing studies will show whether the transmission of CWD into macaques and passage in transgenic mice represents a form of non-adaptive prion amplification, and whether macaque-adapted prions have the potential to infect mice expressing human PrP. The notion that CWD can be transmitted orally into both new-world and old-world non-human primates asks for a careful reevaluation of the zoonotic risk of CWD.
See also poster P103
***> The notion that CWD can be transmitted orally into both new-world and old-world non-human primates asks for a careful reevaluation of the zoonotic risk of CWD.
=====
WA16 Monitoring Potential CWD Transmission to Humans
Belay ED
Centers for Disease Control and Prevention (CDC), National Center for Emerging and Zoonotic Infectious Diseases, Atlanta, GA, USA.
The spread of chronic wasting disease (CWD) in animals has raised concerns about increasing human exposure to the CWD agent via hunting and venison consumption, potentially facilitating CWD transmission to humans. Several studies have explored this possibility, including limited epidemiologic studies, in vitro experiments, and laboratory studies using various types of animal models. Most human exposures to the CWD agent in the United States would be expected to occur in association with deer and elk hunting in CWD-endemic areas. The Centers for Disease Control and Prevention (CDC) collaborated with state health departments in Colorado, Wisconsin, and Wyoming to identify persons at risk of CWD exposure and to monitor their vital status over time. Databases were established of persons who hunted in Colorado and Wyoming and those who reported consumption of venison from deer that later tested positive in Wisconsin. Information from the databases is periodically cross-checked with mortality data to determine the vital status and causes of death for deceased persons. Long-term follow-up of these hunters is needed to assess their risk of development of a prion disease linked to CWD exposure.
=====
P166 Characterization of CJD strain profiles in venison consumers and non-consumers from Alberta and Saskatchewan
Stephanie Booth (1,2), Lise Lamoureux (1), Debra Sorensen (1), Jennifer L. Myskiw (1,2), Megan Klassen (1,2), Michael Coulthart (3), Valerie Sim (4)
(1) Zoonotic Diseases and Special Pathogens, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg (2) Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg (3) Canadian CJD Surveillance System, Public Health Agency of Canada, Ottawa (4) Division of Neurology, Department of Medicine Centre for Prions and Protein Folding Diseases, University of Alberta, Edmonton.
Chronic wasting disease (CWD) is spreading rapidly through wild cervid populations in the Canadian provinces of Alberta and Saskatchewan. While this has implications for tourism and hunting, there is also concern over possible zoonotic transmission to humans who eat venison from infected deer. Whilst there is no evidence of any human cases of CWD to date, the Canadian CJD Surveillance System (CJDSS) in Canada is staying vigilant. When variant CJD occurred following exposure to BSE, the unique biochemical fingerprint of the pathologic PrP enabled a causal link to be confirmed. However, we cannot be sure what phenotype human CWD prions would present with, or indeed, whether this would be distinct from that see in sporadic CJD. Therefore we are undertaking a systematic analysis of the molecular diversity of CJD cases of individuals who resided in Alberta and Saskatchewan at their time of death comparing venison consumers and non-consumers, using a variety of clinical, imaging, pathological and biochemical markers. Our initial objective is to develop novel biochemical methodologies that will extend the baseline glycoform and genetic polymorphism typing that is already completed by the CJDSS. Firstly, we are reviewing MRI, EEG and pathology information from over 40 cases of CJD to select clinically affected areas for further investigation. Biochemical analysis will include assessment of the levels of protease sensitive and resistant prion protein, glycoform typing using 2D gel electrophoresis, testing seeding capabilities and kinetics of aggregation by quaking-induced conversion, and determining prion oligomer size distributions with asymmetric flow field fractionation with in-line light scattering. Progress and preliminary data will be presented. Ultimately, we intend to further define the relationship between PrP structure and disease phenotype and establish a baseline for the identification of future atypical CJD cases that may arise as a result of exposure to CWD.
=====
Source Prion Conference 2018 Abstracts
transmissiblespongiformencephalopathy.blogspot.com/2018/05/prion-2018-may-22-25-2018-santiago-de.html
chronic-wasting-disease.blogspot.com/2018/07/oral-transmission-of-cwd-into.html
prionconference.blogspot.com/2018/
Volume 24, Number 8—August 2018
Research Susceptibility of Human Prion Protein to Conversion by Chronic Wasting Disease Prions
Marcelo A. BarriaComments to Author , Adriana Libori, Gordon Mitchell, and Mark W. Head Author affiliations: National CJD Research and Surveillance Unit, University of Edinburgh, Edinburgh, Scotland, UK (M.A. Barria, A. Libori, M.W. Head); National and OIE Reference Laboratory for Scrapie and CWD, Canadian Food Inspection Agency, Ottawa, Ontario, Canada (G. Mitchell)
Abstract Chronic wasting disease (CWD) is a contagious and fatal neurodegenerative disease and a serious animal health issue for deer and elk in North America. The identification of the first cases of CWD among free-ranging reindeer and moose in Europe brings back into focus the unresolved issue of whether CWD can be zoonotic like bovine spongiform encephalopathy. We used a cell-free seeded protein misfolding assay to determine whether CWD prions from elk, white-tailed deer, and reindeer in North America can convert the human prion protein to the disease-associated form. We found that prions can convert, but the efficiency of conversion is affected by polymorphic variation in the cervid and human prion protein genes. In view of the similarity of reindeer, elk, and white-tailed deer in North America to reindeer, red deer, and roe deer, respectively, in Europe, a more comprehensive and thorough assessment of the zoonotic potential of CWD might be warranted.
snip...
Discussion Characterization of the transmission properties of CWD and evaluation of their zoonotic potential are important for public health purposes. Given that CWD affects several members of the family Cervidae, it seems reasonable to consider whether the zoonotic potential of CWD prions could be affected by factors such as CWD strain, cervid species, geographic location, and Prnp–PRNP polymorphic variation. We have previously used an in vitro conversion assay (PMCA) to investigate the susceptibility of the human PrP to conversion to its disease-associated form by several animal prion diseases, including CWD (15,16,22). The sensitivity of our molecular model for the detection of zoonotic conversion depends on the combination of 1) the action of proteinase K to degrade the abundant human PrPC that constitutes the substrate while only N terminally truncating any human PrPres produced and 2) the presence of the 3F4 epitope on human but not cervid PrP. In effect, this degree of sensitivity means that any human PrPres formed during the PMCA reaction can be detected down to the limit of Western blot sensitivity. In contrast, if other antibodies that detect both cervid and human PrP are used, such as 6H4, then newly formed human PrPres must be detected as a measurable increase in PrPres over the amount remaining in the reaction product from the cervid seed. Although best known for the efficient amplification of prions in research and diagnostic contexts, the variation of the PMCA method employed in our study is optimized for the definitive detection of zoonotic reaction products of inherently inefficient conversion reactions conducted across species barriers. By using this system, we previously made and reported the novel observation that elk CWD prions could convert human PrPC from human brain and could also convert recombinant human PrPC expressed in transgenic mice and eukaryotic cell cultures (15).
A previous publication suggested that mule deer PrPSc was unable to convert humanized transgenic substrate in PMCA assays (23) and required a further step of in vitro conditioning in deer substrate PMCA before it was able to cross the deer–human molecular barrier (24). However, prions from other species, such as elk (15) and reindeer affected by CWD, appear to be compatible with the human protein in a single round of amplification (as shown in our study). These observations suggest that different deer species affected by CWD could present differing degrees of the olecular compatibility with the normal form of human PrP.
The contribution of the polymorphism at codon 129 of the human PrP gene has been extensively studied and is recognized as a risk factor for Creutzfeldt-Jakob disease (4). In cervids, the equivalent codon corresponds to the position 132 encoding methionine or leucine. This polymorphism in the elk gene has been shown to play an important role in CWD susceptibility (25,26). We have investigated the effect of this cervid Prnp polymorphism on the conversion of the humanized transgenic substrate according to the variation in the equivalent PRNP codon 129 polymorphism. Interestingly, only the homologs methionine homozygous seed–substrate reactions could readily convert the human PrP, whereas the heterozygous elk PrPSc was unable to do so, even though comparable amounts of PrPres were used to seed the reaction. In addition, we observed only low levels of human PrPres formation in the reactions seeded with the homozygous methionine (132 MM) and the heterozygous (132 ML) seeds incubated with the other 2 human polymorphic substrates (129 MV and 129 VV). The presence of the amino acid leucine at position 132 of the elk Prnp gene has been attributed to a lower degree of prion conversion compared with methionine on the basis of experiments in mice made transgenic for these polymorphic variants (26). Considering the differences observed for the amplification of the homozygous human methionine substrate by the 2 polymorphic elk seeds (MM and ML), reappraisal of the susceptibility of human PrPC by the full range of cervid polymorphic variants affected by CWD would be warranted.
In light of the recent identification of the first cases of CWD in Europe in a free-ranging reindeer (R. tarandus) in Norway (2), we also decided to evaluate the in vitro conversion potential of CWD in 2 experimentally infected reindeer (18). Formation of human PrPres was readily detectable after a single round of PMCA, and in all 3 humanized polymorphic substrates (MM, MV, and VV). This finding suggests that CWD prions from reindeer could be more compatible with human PrPC generally and might therefore present a greater risk for zoonosis than, for example, CWD prions from white-tailed deer. A more comprehensive comparison of CWD in the affected species, coupled with the polymorphic variations in the human and deer PRNP–Prnp genes, in vivo and in vitro, will be required before firm conclusions can be drawn. Analysis of the Prnp sequence of the CWD reindeer in Norway was reported to be identical to the specimens used in our study (2). This finding raises the possibility of a direct comparison of zoonotic potential between CWD acquired in the wild and that produced in a controlled laboratory setting. (Table).
The prion hypothesis proposes that direct molecular interaction between PrPSc and PrPC is necessary for conversion and prion replication. Accordingly, polymorphic variants of the PrP of host and agent might play a role in determining compatibility and potential zoonotic risk. In this study, we have examined the capacity of the human PrPC to support in vitro conversion by elk, white-tailed deer, and reindeer CWD PrPSc. Our data confirm that elk CWD prions can convert the human PrPC, at least in vitro, and show that the homologous PRNP polymorphisms at codon 129 and 132 in humans and cervids affect conversion efficiency. Other species affected by CWD, particularly caribou or reindeer, also seem able to convert the human PrP. It will be important to determine whether other polymorphic variants found in other CWD-affected Cervidae or perhaps other factors (17) exert similar effects on the ability to convert human PrP and thus affect their zoonotic potential.
Dr. Barria is a research scientist working at the National CJD Research and Surveillance Unit, University of Edinburgh. His research has focused on understanding the molecular basis of a group of fatal neurologic disorders called prion diseases.
Acknowledgments We thank Aru Balachandran for originally providing cervid brain tissues, Abigail Diack and Jean Manson for providing mouse brain tissue, and James Ironside for his critical reading of the manuscript at an early stage.
This report is independent research commissioned and funded by the United Kingdom’s Department of Health Policy Research Programme and the Government of Scotland. The views expressed in this publication are those of the authors and not necessarily those of the Department of Health or the Government of Scotland.
Author contributions: The study was conceived and designed by M.A.B. and M.W.H. The experiments were conducted by M.A.B. and A.L. Chronic wasting disease brain specimens were provided by G.M. The manuscript was written by M.A.B. and M.W.H. All authors contributed to the editing and revision of the manuscript.
wwwnc.cdc.gov/eid/article/24/8/16-1888_article
www.ed.ac.uk/clinical-brain-sciences/news/news-jul-dec-2018/cwd-prions-human-conversion
Prion 2017 Conference Abstracts
First evidence of intracranial and peroral transmission of Chronic Wasting Disease (CWD) into Cynomolgus macaques: a work in progress
Stefanie Czub1, Walter Schulz-Schaeffer2, Christiane Stahl-Hennig3, Michael Beekes4, Hermann Schaetzl5 and Dirk Motzkus6 1 University of Calgary Faculty of Veterinary Medicine/Canadian Food Inspection Agency; 2Universitatsklinikum des Saarlandes und Medizinische Fakultat der Universitat des Saarlandes; 3 Deutsches Primaten Zentrum/Goettingen; 4 Robert-Koch-Institut Berlin; 5 University of Calgary Faculty of Veterinary Medicine; 6 presently: Boehringer Ingelheim Veterinary Research Center; previously: Deutsches Primaten Zentrum/Goettingen
This is a progress report of a project which started in 2009.
21 cynomolgus macaques were challenged with characterized CWD material from white-tailed deer (WTD) or elk by intracerebral (ic), oral, and skin exposure routes. Additional blood transfusion experiments are supposed to assess the CWD contamination risk of human blood product. Challenge materials originated from symptomatic cervids for ic, skin scarification and partially per oral routes (WTD brain). Challenge material for feeding of muscle derived from preclinical WTD and from preclinical macaques for blood transfusion experiments. We have confirmed that the CWD challenge material contained at least two different CWD agents (brain material) as well as CWD prions in muscle-associated nerves. Here we present first data on a group of animals either challenged ic with steel wires or per orally and sacrificed with incubation times ranging from 4.5 to 6.9 years at postmortem. Three animals displayed signs of mild clinical disease, including anxiety, apathy, ataxia and/or tremor. In four animals wasting was observed, two of those had confirmed diabetes. All animals have variable signs of prion neuropathology in spinal cords and brains and by supersensitive IHC, reaction was detected in spinal cord segments of all animals. Protein misfolding cyclic amplification (PMCA), real-time quaking-induced conversion (RT-QuiC) and PET-blot assays to further substantiate these findings are on the way, as well as bioassays in bank voles and transgenic mice. At present, a total of 10 animals are sacrificed and read-outs are ongoing. Preclinical incubation of the remaining macaques covers a range from 6.4 to 7.10 years. Based on the species barrier and an incubation time of > 5 years for BSE in macaques and about 10 years for scrapie in macaques, we expected an onset of clinical disease beyond 6 years post inoculation.
PRION 2017 DECIPHERING NEURODEGENERATIVE DISORDERS ABSTRACTS REFERENCE
aabb.confex.com/aabb/2018/mediafile/Handout/Session2756/TU1-3.pdf
8. Even though human TSE‐exposure risk through consumption of game from European cervids can be assumed to be minor, if at all existing, no final conclusion can be drawn due to the overall lack of scientific data. In particular the US data do not clearly exclude the possibility of human (sporadic or familial) TSE development due to consumption of venison. The Working Group thus recognizes a potential risk to consumers if a TSE would be present in European cervids. It might be prudent considering appropriate measures to reduce such a risk, e.g. excluding tissues such as CNS and lymphoid tissues from the human food chain, which would greatly reduce any potential risk for consumers. However, it is stressed that currently, no data regarding a risk of TSE infections from cervid products are available.
efsa.onlinelibrary.wiley.com/doi/full/10.2903/j.efsa.2018.5132
SATURDAY, FEBRUARY 23, 2019
Chronic Wasting Disease CWD TSE Prion and THE FEAST 2003 CDC an updated review of the science 2019
chronic-wasting-disease.blogspot.com/2019/02/chronic-wasting-disease-cwd-tse-prion.html
TUESDAY, NOVEMBER 04, 2014
Six-year follow-up of a point-source exposure to CWD contaminated venison in an Upstate New York community: risk behaviours and health outcomes 2005–2011 Authors, though, acknowledged the study was limited in geography and sample size and so it couldn't draw a conclusion about the risk to humans. They recommended more study. Dr. Ermias Belay was the report's principal author but he said New York and Oneida County officials are following the proper course by not launching a study. "There's really nothing to monitor presently. No one's sick," Belay said, noting the disease's incubation period in deer and elk is measured in years. "
chronic-wasting-disease.blogspot.com/2014/11/six-year-follow-up-of-point-source.html
Transmission Studies Mule deer transmissions of CWD were by intracerebral inoculation and compared with natural cases {the following was written but with a single line marked through it ''first passage (by this route)}....TSS resulted in a more rapidly progressive clinical disease with repeated episodes of synocopy ending in coma. One control animal became affected, it is believed through contamination of inoculum (?saline). Further CWD transmissions were carried out by Dick Marsh into ferret, mink and squirrel monkey. Transmission occurred in ALL of these species with the shortest incubation period in the ferret.
snip....
web.archive.org/web/20090506002237/http://www..bseinquiry.gov.uk/files/mb/m11b/tab01.pdf
Prion Infectivity in Fat of Deer with Chronic Wasting Disease▿
Brent Race#, Kimberly Meade-White#, Richard Race and Bruce Chesebro* + Author Affiliations In mice, prion infectivity was recently detected in fat. Since ruminant fat is consumed by humans and fed to animals, we determined infectivity titers in fat from two CWD-infected deer. Deer fat devoid of muscle contained low levels of CWD infectivity and might be a risk factor for prion infection of other species.
jvi.asm.org/content/83/18/9608.full Prions in Skeletal Muscles of Deer with Chronic Wasting Disease Here bioassays in transgenic mice expressing cervid prion protein revealed the presence of infectious prions in skeletal muscles of CWD-infected deer, demonstrating that humans consuming or handling meat from CWD-infected deer are at risk to prion exposure.
science.sciencemag.org/content/311/5764/1117..long
*** now, let’s see what the authors said about this casual link, personal communications years ago, and then the latest on the zoonotic potential from CWD to humans from the TOKYO PRION 2016 CONFERENCE.
see where it is stated NO STRONG evidence. so, does this mean there IS casual evidence
?“Our conclusion stating that we found no strong evidence of CWD transmission to humans”
From: TSS Subject: CWD aka MAD DEER/ELK TO HUMANS
Date: September 30, 2002 at 7:06 am PST
From: "Belay, Ermias"
To: Cc: "Race, Richard (NIH)" ; ; "Belay, Ermias"
Sent: Monday, September 30, 2002 9:22 AM
Subject: RE: TO CDC AND NIH - PUB MED- 3 MORE DEATHS - CWD - YOUNG HUNTERS
Dear Sir/Madam, In the Archives of Neurology you quoted (the abstract of which was attached to your email), we did not say CWD in humans will present like variant CJD.. That assumption would be wrong. I encourage you to read the whole article and call me if you have questions or need more clarification (phone: 404-639-3091).
Also, we do not claim that "no-one has ever been infected with prion disease from eating venison." Our conclusion stating that we found no strong evidence of CWD transmission to humans in the article you quoted or in any other forum is limited to the patients we investigated.
Ermias Belay, M.D. Centers for Disease Control and Prevention
-----Original Message----- From:
Sent: Sunday, September 29, 2002 10:15 AM
To: rr26k@nih.gov; rrace@niaid.nih.gov; ebb8@CDC.GOV
Subject: TO CDC AND NIH - PUB MED- 3 MORE DEATHS - CWD - YOUNG HUNTERS
Sunday, November 10, 2002 6:26 PM .......snip........end..............TSS
Thursday, April 03, 2008
A prion disease of cervids: Chronic wasting disease 2008 1: Vet Res. 2008 Apr 3;39(4):41 A prion disease of cervids: Chronic wasting disease Sigurdson CJ.
snip... *** twenty-seven CJD patients who regularly consumed venison were reported to the Surveillance Center***,
snip... full text ;
chronic-wasting-disease.blogspot.com/2008/04/prion-disease-of-cervids-chronic.html
> However, to date, no CWD infections have been reported in people.
sporadic, spontaneous CJD, 85%+ of all human TSE, did not just happen. never in scientific literature has this been proven. if one looks up the word sporadic or spontaneous at pubmed, you will get a laundry list of disease that are classified in such a way;
sporadic = 54,983 hits
www.ncbi.nlm.nih.gov/pubmed/?term=sporadic
spontaneous = 325,650 hits
www.ncbi.nlm.nih.gov/pubmed/?term=spontaneous
key word here is 'reported'. science has shown that CWD in humans will look like sporadic CJD.
SO, how can one assume that CWD has not already transmitted to humans? they can't, and it's as simple as that. from all recorded science to date, CWD has already transmitted to humans, and it's being misdiagnosed as sporadic CJD. ...terry
*** LOOKING FOR CWD IN HUMANS AS nvCJD or as an ATYPICAL CJD, LOOKING IN ALL THE WRONG PLACES $$$ ***
> However, to date, no CWD infections have been reported in people. key word here is ‘reported’. science has shown that CWD in humans will look like sporadic CJD. SO, how can one assume that CWD has not already transmitted to humans? they can’t, and it’s as simple as that. from all recorded science to date, CWD has already transmitted to humans, and it’s being misdiagnosed as sporadic CJD. …terry
*** LOOKING FOR CWD IN HUMANS AS nvCJD or as an ATYPICAL CJD, LOOKING IN ALL THE WRONG PLACES $$$ ***
*** 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).***
www.tandfonline.com/doi/full/10.4161/pri.28124?src=recsys
www.tandfonline.com/doi/pdf/10.4161/pri.28124?needAccess=true
wwwnc.cdc.gov/eid/article/20/1/13-0858_article
CWD TSE PRION AND ZOONOTIC, ZOONOSIS, FACTORS
Subject: Re: DEER SPONGIFORM ENCEPHALOPATHY SURVEY & HOUND STUDY
Date: Fri, 18 Oct 2002 23:12:22 +0100
From: Steve Dealler
Reply-To: Bovine Spongiform Encephalopathy Organization: Netscape Online member
To: BSE-L@ References:
Dear Terry,
An excellent piece of review as this literature is desperately difficult to get back from Government sites.
What happened with the deer was that an association between deer meat eating and sporadic CJD was found in about 1993. The evidence was not great but did not disappear after several years of asking CJD cases what they had eaten. I think that the work into deer disease largely stopped because it was not helpful to the UK industry...and no specific cases were reported. Well, if you dont look adequately like they are in USA currenly then you wont find any!
Steve Dealler
====
caninespongiformencephalopathy.blogspot.com/2010/03/canine-spongiform-encephalopathy-aka.html
''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).''
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 ;
web.archive.org/web/20090506050043/http://www.bseinquiry.gov.uk/files/yb/1994/08/00004001.pdf
web.archive.org/web/20090506050007/http://www.bseinquiry.gov.uk/files/yb/1994/10/00003001.pdf
web.archive.org/web/20090506050244/http://www.bseinquiry.gov.uk/files/yb/1994/07/00001001.pdf
Stephen Dealler is a consultant medical microbiologist deal@airtime.co.uk
BSE Inquiry Steve Dealler
Management In Confidence
BSE: Private Submission of Bovine Brain Dealler
snip...see full text;
MONDAY, FEBRUARY 25, 2019
***> MAD DOGS AND ENGLISHMEN BSE, SCRAPIE, CWD, CJD, TSE PRION A REVIEW 2019
bseinquiry.blogspot.com/2019/02/mad-dogs-and-englishmen-bse-scrapie-cwd.html
***> ''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).''
***> In conclusion, sensory symptoms and loss of reflexes in Gerstmann-Sträussler-Scheinker syndrome can be explained by neuropathological changes in the spinal cord. We conclude that the sensory symptoms and loss of lower limb reflexes in Gerstmann-Sträussler-Scheinker syndrome is due to pathology in the caudal spinal cord. <***
***> The clinical and pathological presentation in macaques was mostly atypical, with a strong emphasis on spinal cord pathology.<***
***> The notion that CWD can be transmitted orally into both new-world and old-world non-human primates asks for a careful reevaluation of the zoonotic risk of CWD. <***
***> All animals have variable signs of prion neuropathology in spinal cords and brains and by supersensitive IHC, reaction was detected in spinal cord segments of all animals.<***
***> In particular the US data do not clearly exclude the possibility of human (sporadic or familial) TSE development due to consumption of venison. The Working Group thus recognizes a potential risk to consumers if a TSE would be present in European cervids.'' Scientific opinion on chronic wasting disease (II) <***
familialcjdtseprion.blogspot.com/2019/02/cwd-gss-tse-prion-spinal-cord-confucius.html
***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.***
Even if the prevailing view is that sporadic CJD is due to the spontaneous formation of CJD prions, it remains possible that its apparent sporadic nature may, at least in part, result from our limited capacity to identify an environmental origin.
www.nature.com/articles/srep11573
cwd scrapie pigs oral routes, oh my!
***> However, at 51 months of incubation or greater, 5 animals were positive by one or more diagnostic methods. Furthermore, positive bioassay results were obtained from all inoculated groups (oral and intracranial; market weight and end of study) suggesting that swine are potential hosts for the agent of scrapie. <***
>*** Although the current U.S. feed ban is based on keeping tissues from TSE infected cattle from contaminating animal feed, swine rations in the U.S. could contain animal derived components including materials from scrapie infected sheep and goats. These results indicating the susceptibility of pigs to sheep scrapie, coupled with the limitations of the current feed ban, indicates that a revision of the feed ban may be necessary to protect swine production and potentially human health. <***
***> Results: PrPSc was not detected by EIA and IHC in any RPLNs. All tonsils and MLNs were negative by IHC, though the MLN from one pig in the oral <6 month group was positive by EIA. PrPSc was detected by QuIC in at least one of the lymphoid tissues examined in 5/6 pigs in the intracranial <6 months group, 6/7 intracranial >6 months group, 5/6 pigs in the oral <6 months group, and 4/6 oral >6 months group. Overall, the MLN was positive in 14/19 (74%) of samples examined, the RPLN in 8/18 (44%), and the tonsil in 10/25 (40%).
***> Conclusions: This study demonstrates that PrPSc accumulates in lymphoid tissues from pigs challenged intracranially or orally with the CWD agent, and can be detected as early as 4 months after challenge. CWD-infected pigs rarely develop clinical disease and if they do, they do so after a long incubation period. This raises the possibility that CWD-infected pigs could shed prions into their environment long before they develop clinical disease. Furthermore, lymphoid tissues from CWD-infected pigs could present a potential source of CWD infectivity in the animal and human food chains.
www.ars.usda.gov/research/publications/publication/?seqNo115=353091
www.ars.usda.gov/research/project/?accnNo=432011&fy=2017
www.ars.usda.gov/research/publications/publication/?seqNo115=337105
CONFIDENTIAL
EXPERIMENTAL PORCINE SPONGIFORM ENCEPHALOPATHY
LINE TO TAKE
3. If questions on pharmaceuticals are raised at the Press conference, the suggested line to take is as follows:-
"There are no medicinal products licensed for use on the market which make use of UK-derived porcine tissues with which any hypothetical “high risk" ‘might be associated. The results of the recent experimental work at the CSM will be carefully examined by the CSM‘s Working Group on spongiform encephalopathy at its next meeting.
DO Hagger RM 1533 MT Ext 3201
web.archive.org/web/20030822054419/www.bseinquiry.gov.uk/files/yb/1990/09/21009001.pdf
While this clearly is a cause for concern we should not jump to the conclusion that this means that pigs will necessarily be infected by bone and meat meal fed by the oral route as is the case with cattle. ...
web.archive.org/web/20031026000118/www.bseinquiry.gov.uk/files/yb/1990/08/23004001.pdf
we cannot rule out the possibility that unrecognised subclinical spongiform encephalopathy could be present in British pigs though there is no evidence for this: only with parenteral/implantable pharmaceuticals/devices is the theoretical risk to humans of sufficient concern to consider any action.
web.archive.org/web/20030822031154/www.bseinquiry.gov.uk/files/yb/1990/09/10007001.pdf
May I, at the outset, reiterate that we should avoid dissemination of papers relating to this experimental finding to prevent premature release of the information. ...
web.archive.org/web/20030822052332/www.bseinquiry.gov.uk/files/yb/1990/09/11005001.pdf
3. It is particularly important that this information is not passed outside the Department, until Ministers have decided how they wish it to be handled. ...
web.archive.org/web/20030822052438/www.bseinquiry.gov.uk/files/yb/1990/09/12002001.pdf
But it would be easier for us if pharmaceuticals/devices are not directly mentioned at all. ...
web.archive.org/web/20030518170213/www.bseinquiry.gov.uk/files/yb/1990/09/13004001.pdf
Our records show that while some use is made of porcine materials in medicinal products, the only products which would appear to be in a hypothetically ''higher risk'' area are the adrenocorticotrophic hormone for which the source material comes from outside the United Kingdom, namely America China Sweden France and Germany. The products are manufactured by Ferring and Armour. A further product, ''Zenoderm Corium implant'' manufactured by Ethicon, makes use of porcine skin - which is not considered to be a ''high risk'' tissue, but one of its uses is described in the data sheet as ''in dural replacement''. This product is sourced from the United Kingdom.....
web.archive.org/web/20030822054419/www.bseinquiry.gov.uk/files/yb/1990/09/21009001.pdf
Distribution CWD North America
www.usgs.gov/media/images/distribution-chronic-wasting-disease-north-america-0
Research Project: Elucidating the Pathobiology and Transmission of Transmissible Spongiform Encephalopathies Location: Virus and Prion Research
2023 Annual Report
snip...
Accomplishments
1. Sheep scrapie agent can infect white-tailed deer after oronasal exposure. The origin of chronic wasting disease (CWD) is not known, but it has many similarities to the prion disease of sheep called scrapie. It has long been hypothesized that CWD could have arisen through transmission of sheep scrapie to deer. ARS researches in Ames, Iowa, conducted a study to determine if scrapie derived from sheep could be transmitted to white-tailed deer. This study reports that the deer inoculated with sheep scrapie developed clinical signs of TSE and that the abnormal prion protein could be detected in a wide range of neural and lymphoid tissues. These results indicate that deer may be susceptible to sheep scrapie if exposed to the disease in natural or agricultural settings. In addition, several strong similarities between CWD in white-tailed deer and the experimental cases of scrapie in white-tailed deer in this report suggest that it would be difficult to identify scrapie in deer were a case to occur. This information should be considered when developing plans to reduce or eliminate TSEs or advising farmers that wish to keep their deer herds free from prion diseases.
2. A novel sampling method was developed for monitoring CWD in farmed cervids to help maintain a CWD free environment. While the transmissible spongiform encephalopathies (TSEs) scrapie and bovine spongiform encephalopathy (BSE) have been largely controlled through selective breeding and a ruminant feed ban respectively, neither approach is applicable to chronic wasting disease (CWD).
www.ars.usda.gov/research/project/?accnNo=440677&fy=2023
Terry S. Singeltary Sr.