Missouri MDC REPORTS FINAL CWD RESULTS FOR 2020-2021 44 POSITIVE WITH TOTAL TO DATE 206 CONFIRMED
Missouri MDC REPORTS FINAL CWD RESULTS FOR 2020-2021 44 POSITIVE WITH TOTAL TO DATE 206 CONFIRMED
MDC REPORTS FINAL CWD RESULTS FOR 2020-2021 SEASON
News from the region: Statewide
Joe JerekApr 26, 2021 JEFFERSON CITY, Mo. – The Missouri Department of Conservation (MDC) reports it has completed its monitoring, management, and testing efforts for its 2020-2021 chronic wasting disease (CWD) surveillance year. From those efforts, MDC reports it collected more than 15,300 tissue samples from mostly hunter-harvested deer for CWD testing. MDC has confirmed 44 new cases of CWD from the deer tested.
The new findings bring the total number of CWD cases in the state to 206. MDC has tested more than 152,300 deer since the first cases of CWD were found in free-ranging deer in Missouri in 2012.
Of the 44 new cases, two were found in Putnam County and one in Pulaski County, both of which had no previously known cases of CWD.
The 44 new cases of CWD were found in the following counties: Adair (2), Franklin (5), Jefferson (5), Linn (6), Macon (5), Oregon (3), Polk (1), Pulaski (1), Putnam (2), St Clair (1), Ste Genevieve (12), and Stone (1).
One confirmed case came from a deer in Ste. Genevieve County that was found exhibiting signs of CWD infection. The sick deer was observed by several people, and MDC was notified. The sick deer was humanely shot by MDC staff and a tissue sample was submitted for CWD testing. MDC staff properly disposed of the carcass.
It typically takes an average 18-24 months from the time a deer is infected with CWD until it looks visibly sick. Deer can spread CWD long before they look or act sick. In Missouri, most deer that test CWD-positive do not show signs of the disease. Deer showing signs of CWD may present a variety of symptoms, including dramatic weight loss, abnormal behavior, and excessive thirst, drooling, or urination.
MDC Wildlife Health Program Supervisor Jasmine Batten noted that the 15,300 deer tested during the past season decreased significantly from the year before due to the effects of COVID-19 on MDC’s surveillance efforts.
“We tested about 16,000 fewer deer last season compared to the 2019-2020 testing period,” Batten said. “The lower number of deer tested this season was mostly due to MDC suspending our mandatory sampling requirements during the opening weekend due to concerns about human health and safety related to the COVDID-19 pandemic. Thankfully, the hard work of taxidermists and meat processors who provided samples and the hunters who voluntarily had their deer sampled at a variety of locations allowed us to still adequately monitor and detect CWD throughout the state.”
MDC thanks the thousands of hunters who brought their harvested deer to MDC locations for CWD sampling and testing. MDC also thanks the more than 150 partnering taxidermists and meat processors throughout the state who sampled over 9,300 hunter-harvested deer this year for CWD testing.
MDC also thanks the more than 1,500 landowners in areas where CWD has been found who voluntarily signed up to participate in MDC’s post-deer season CWD management efforts. Cooperatively, landowners and MDC staff in these areas harvested an additional 2,713 deer after the close of the deer season, removing an additional 18 CWD-positive deer.
All deer harvested through the post-deer season CWD management efforts that did not test positive for CWD were either returned to the landowner or donated to local food pantries through the Share the Harvest venison-donation program. More than 80,000 pounds of venison were donated to Share the Harvest from last season’s efforts.
According to MDC, post-deer season targeted culling efforts can help decrease CWD transmission by reducing the number of potentially infected deer within areas where the disease has been detected. Long-term, sustained, targeted culling has been shown to slow the spread of CWD, and MDC is committed to using this management tool to protect the state’s deer herd from the effects of CWD.
CWD is a deadly disease in white-tailed deer and other members of the deer family. The purpose of MDC’s CWD sampling efforts is to find cases as early as possible so the Department can limit the spread of the disease by implementing management actions such as targeted culling. For more information on MDC’s 2020-2021 CWD surveillance results, visit mdc.mo.gov/cwd under CWD Surveillance.
WEDNESDAY, MAY 06, 2020
Missouri 46 new cases Chronic Wasting Disease found, total to date at 162 documented CWD
MDC REPORTS FINAL CWD RESULTS FOR 2019-2020 SEASON
News from the region: Statewide Joe JerekMay 06, 2020 JEFFERSON CITY, Mo. – The Missouri Department of Conservation (MDC) reports it has completed its monitoring and testing efforts for the 2019-2020 chronic wasting disease (CWD) surveillance year. From those efforts, MDC reports it has confirmed 46 new cases of the deadly deer disease.
These new findings bring the total number of CWD cases in the state to 162. MDC has tested more than 137,000 deer since the first cases of CWD were found in free-ranging deer in Missouri in 2012. https://mdc.mo.gov/newsroom/mdc-reports-final-cwd-results-2019-2020-season
Missouri 2019 - 2020 CWD
WEDNESDAY, MAY 06, 2020
Missouri 46 new cases Chronic Wasting Disease found, total to date at 162 documented CWD
TUESDAY, FEBRUARY 11, 2020
Missouri MDC 2019-2020 SAMPLING RESULTS CWD TSE PRION TO DATE 28 Positive
SUNDAY, JANUARY 19, 2020
Missouri CWD TSE Prion 2019-2020 SAMPLING RESULTS TO DATE 25 Positive
THURSDAY, JANUARY 02, 2020
Missouri MDC officially reports more than 20 new cases of Chronic Wasting Disease CWD TSE Prion
APHIS Announces Availability of Funding to Control and Prevent Chronic Wasting Disease
CWD Funding Availability USDA Animal and Plant Health Inspection Service CWD Funding Availability Contact: APHISpress@usda.gov
WASHINGTON, April 20, 2021. The U.S. Department of Agriculture’s Animal and Plant Health Inspection Service (APHIS) is making available up to $5.6 million for states and Tribal governments to further develop and implement Chronic Wasting Disease (CWD) management and response activities in wild and farmed cervids (e.g., deer, elk).
State departments of agriculture, state animal health agencies, state departments of wildlife or natural resources, and Federally recognized Native American Tribal governments and organizations are eligible to submit funding proposals that further develop and implement CWD management, response and research activities, including surveillance and testing. The funding can also be used to support education and outreach activities to increase awareness about the disease and how it spreads. APHIS may give priority to states and Tribal governments that have already detected CWD or border CWD endemic areas; and have either implemented monitoring and surveillance programs or propose to do so.
“APHIS’ Veterinary Services and Wildlife Services personnel are committed to working with our state and Tribal partners to control and prevent Chronic Wasting Disease in our Nation’s farmed and wild cervids,” APHIS Administrator Kevin Shea said. “These collaborative efforts will strengthen our ability to find and implement new solutions as part of our mission to safeguard agriculture and natural resources.”
CWD is an infectious, degenerative disease of cervids that causes brain cells to die, ultimately leading to the death of the affected animal. The incubation period can be long depending on species and genetic factors. Infected animals look healthy until the end stages of the disease, making them difficult to distinguish from healthy animals. Animals infected with CWD can transmit the disease to other animals during the “silent” incubation period. The disease has spread widely and the limited number of tools, as well as tool effectiveness, impacts the ability to effectively control the disease.
An eligible applicant may submit multiple proposals for each funding opportunity, requesting up to the maximum amount for that funding opportunity in each proposal. Applications will be reviewed, and funding decisions will be announced prior to October 1, 2021.
Specifically, these cooperative agreement opportunities will allow for state departments of agriculture, state animal health agencies, state departments of wildlife or natural resources and Federally recognized Native American Tribal governments and organizations to further develop and implement CWD management and response activities in accordance with the following priorities:
improving CWD management of affected farmed herds and wild cervid populations; improving CWD management of affected areas or premises; conducting additional research on amplification assays, including the validation of the RT-QuIC assay; conducting additional research on predictive genetics; and, developing and/or delivering educational outreach materials or programs. Funding opportunity announcements are posted on ezFedGrants and Grants.gov and can be found by searching the title, catalog of federal domestic assistance number, or funding opportunity number (see below). Applications are due in June, and specific deadlines vary.
Funding Opportunity Title
Catalog of Federal Domestic Assistance Number
Funding Opportunity Number
Application Due Date
FY21 Farmed Cervid CWD Management and Response Activities
10.025, Plant and Animal Disease, Pest Control and Animal Care
USDA-APHIS-10025-VSSPRS00-21-0108
June 19, 2021 at 11:59 PM Eastern Daylight Savings Time
FY21 Wild Cervid CWD Management and Response Activities
10.028, Wildlife Services
USDA-APHIS-10028-WSNWRC00-21-0008
June 19, 2021 at 11:59 PM Eastern Daylight Savings Time
FY21 Tribal Nations Wild Cervid CWD Opportunities
10.028, Wildlife Services
USDA-APHIS-10028-WSNWRC00-21-0009
July 4, 2021 at 11:59 PM Eastern Daylight Savings Time
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USDA touches the lives of all Americans each day in so many positive ways. In the Biden-Harris Administration, USDA is transforming America’s food system with a greater focus on more resilient local and regional food production, fairer markets for all producers, ensuring access to safe, healthy and nutritious food in all communities, building new markets and streams of income for farmers and producers using climate smart food and forestry practices, making historic investments in infrastructure and clean energy capabilities in rural America, and committing to equity across the Department by removing systemic barriers and building a workforce more representative of America. To learn more, visit www.usda.gov.
2021 Feb 25;22(5):2271. doi: 10.3390/ijms22052271.
Cervid Prion Protein Polymorphisms: Role in Chronic Wasting Disease Pathogenesis
Maria Immaculata Arifin 1 2 3, Samia Hannaoui 1 2 3, Sheng Chun Chang 1 2 3, Simrika Thapa 1 2 3, Hermann M Schatzl 1 2 3, Sabine Gilch 1 2 3 Affiliations expand PMID: 33668798 PMCID: PMC7956812 DOI: 10.3390/ijms22052271 Free PMC article
Abstract
Chronic wasting disease (CWD) is a prion disease found in both free-ranging and farmed cervids. Susceptibility of these animals to CWD is governed by various exogenous and endogenous factors. Past studies have demonstrated that polymorphisms within the prion protein (PrP) sequence itself affect an animal's susceptibility to CWD. PrP polymorphisms can modulate CWD pathogenesis in two ways: the ability of the endogenous prion protein (PrPC) to convert into infectious prions (PrPSc) or it can give rise to novel prion strains. In vivo studies in susceptible cervids, complemented by studies in transgenic mice expressing the corresponding cervid PrP sequence, show that each polymorphism has distinct effects on both PrPC and PrPSc. It is not entirely clear how these polymorphisms are responsible for these effects, but in vitro studies suggest they play a role in modifying PrP epitopes crucial for PrPC to PrPSc conversion and determining PrPC stability. PrP polymorphisms are unique to one or two cervid species and most confer a certain degree of reduced susceptibility to CWD. 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.
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7. Conclusions
CWD is considered the most contagious prion disease. It is spreading efficiently among wild and farmed cervids, resulting in increasing case numbers and an expansion in geographic distribution. Principally, all cervid species that are currently exposed to CWD are highly susceptible to infection and clinical disease, but species-specific polymorphisms in Prnp on one or both alleles result in single amino acid substitutions in the PrP and modulate pathogenesis. In most cases, the presence of only one mutated allele extends the incubation period of infected animals. It is tempting to speculate whether breeding schemes selecting for animals with a genetic background of lower CWD susceptibility could be introduced as a management strategy to curb the spread of CWD, a practice that was successfully applied to manage scrapie in sheep. However, it is important to keep in mind that there is no absolute resistance to infection, and animals carrying less susceptible genotypes still propagate infectious prions and might shed them for a longer period of time during extended incubation. Datasets from experimental infection schemes of cervids carrying less susceptible genotypes addressing shedding are critically important but very limited, mostly due to the low number of animals with non-wild type genotypes in those studies. Another caveat is the emergence of a growing variety of PrPCWD strains. Initially, it appeared that strain diversity in CWD is limited to basically two strains. In recent years, however, more PrPCWD strains were isolated mostly from cervids expressing PrP with a polymorphism (e.g., H95+ , 116AG, 132L), demonstrating another significant role of PrPC primary structure variations in CWD pathogenesis. The main concern with these findings is that strains can have distinct host ranges, and for some of them clinical disease was achieved in a mouse model previously considered resistant to various PrPCWD isolates. An expanded host range may not only cause increased transmission among cervids, but also transmission to sympatric species, livestock and humans. Recent evidence suggests some zoonotic potential of CWD, raising concerns as hunting, which is popular in North America and Scandinavia, and widespread consumption of venison exposes people to CWD.
It is clearly recognizable that cervid Prnp polymorphisms add an additional layer of complexity for management and risk assessment of CWD. Samples obtained for CWD surveillance can and should be utilized not only for CWD testing, but also for genotyping, strain typing, and transmission studies. Altogether, solving CWD-associated challenges calls for a One Health approach encompassing collaboration between molecular and wildlife biologists, social scientists, and regulators to eventually contain the spread and reduce the risks to ecosystem, animal, and human health.
Author Contributions: M.I.A., S.H., S.C.C., S.T., and S.G. wrote the paper; S.G. and M.I.A. designed the content; S.G. and H.M.S. provided comments and edits to the manuscript. All authors read and edited the final manuscript. All authors have read and agreed to the published version of the manuscript.
Funding: This research received no external funding.
Acknowledgments: We are grateful to the Alberta Prion Research Institute, Genome Canada, Genome Alberta and the University of Calgary for funding. S.G. is supported by the Canada Research Chairs program. M.I.A. acknowledges support through the Alberta Graduate Excellence Scholarship. Conflicts of Interest: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.
References
Keywords: cervid; chronic wasting disease; pathogenesis; polymorphism; prion protein; strain.
Conflict of interest statement
The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.
Implications of farmed-cervid movements on the transmission of chronic wasting disease
Author links open overlay panel Dennis N.Makau KimberlyVanderWaalJamesKincheloeScott J.Wells
Abstract
Chronic wasting disease is a transmissible spongiform encephalopathy that affects cervids with a clinical picture of muscle wasting in infected animals. The objective of this study was to quantify movement patterns of farmed cervids in the state of Minnesota as a model for identifying potential disease mitigation points. Time aggregated network analysis was performed on data consisting of 1221 intra-state cervid movements from farms located within Minnesota (n = 432 farms). Intra-state movements accounted for 48.2 % of all documented movements (2578) in Minnesota from 2013 to 2018; the remaining movements were inter-state. Annual networks were sparse in nature with low graph densities (6.9 × 10−4 - 1.4 × 10-3) and transitivity (0.06−0.12). Frequency of movements increased significantly (p < 0.05) in the months of September and October before decreasing in November, which coincided with the breeding and hunting seasons. Some of these contacts were as far as 500 km apart. The median length of infection chains for CWD positive farms was estimated to be 5.0 and 6.0 farms in-and out-going infection chains, respectively. A k-test analysis demonstrated that the observed median number of infected farms directly connected to other infected farms was 2.0, which was significantly higher than a fortuitous event (p = 0.002). Movements of cervids between farms were largely unpredictable with very low edge overlap (mean 0.02 %) from year to year, suggesting that persistent commercial relationships among farms were rare. In conclusion, long distance trade movements present a risk for spread of chronic wasting disease in Minnesota. The sparse networks and unpredictable farm contacts could be because cervid production is not as vertically integrated as other species-differentiated and established industries, such as swine or poultry. Our analytical approach can be used to understand chronic wasting disease in other states in the U.S. and North America in general.
Introduction
Chronic Wasting Disease (CWD) is a prion disease that affects cervids and has been widely observed in both farmed/captive and wild species of the deer family (Bourne, 2015). The disease is a transmissible spongiform encephalopathy (TSE) in which most lesions are observed in brain tissue at necropsy, though the infective agent can be isolated from other body tissues and organs (Gilch et al., 2011). Clinical presentation of the disease is primarily behavioral in the early stages before progressing to muscular wasting in the infected animal. Some of the behavioral symptoms include polydipsia, polyuria, locomotor deficiencies, hypersalivation and low head carriage (Glich, 2019). The incubation and spread of the infection occurs through the lymphatic system of the animal (Bourne, 2015) and could take more than 17 months (Argue et al., 2007). The disease has been observed for more than 50 years in free-ranging/wild cervid populations in the U.S. in the states of Colorado and Wyoming (Carlson et al., 2018; Machado et al., 2019). The distribution of CWD is expanding and recent positive cases have been detected in both wild free-ranging cervids and farmed/captive cervids in the Canadian provinces of Saskatchewan and Alberta and in 24 states in the U.S. including Minnesota and Wisconsin (Cosgrove, 2017; Machado et al., 2019).
Horizontal transmission has been identified as a crucial pathway through which the infection is maintained in cervid populations (Moore et al., 2016). Horizontal transmission includes direct contact between healthy and infected animals (or their tissues) and indirect contacts such as interaction with contaminated feed, water, and other fomites (Gilch et al., 2011). It is not easy to identify sources of infection via indirect contact routes due to environmental persistence of prions and the ability to contaminate plants and other materials (Pritzkow et al., 2015, 2018).
Although there has been no evidence of zoonotic CWD cases (Gilch et al., 2011; Hannaoui et al., 2017), the disease has a high economic impact on the cervid farming industry in North America, especially due to associated regulatory costs. Arnot et al. (2009) estimated value risks of up to $12 million annually in increased biosecurity and biosafety interventions on farms in Canada. Moreover, consistent impact of CWD infections has the potential to greatly impact the Canadian agriculture industries and economic contribution nationally (Petigara et al., 2011). In the U.S., the potential costs and associated losses have been estimated to be up to $83 million annually (Bishop, 2010). In realization of the threat of CWD to the economy, surveillance and monitoring protocols have been instituted by the two countries to prevent spread of the disease (Rosatte et al., 2014; Cosgrove, 2017; Gillin and Mawdsley, 2018; Angadjivand and Crafton, 2019; Canadian Food Inspection Agency, 2019).
CWD’s long incubation period coupled with multiple transmission pathways, including movement of farmed/captive cervids across the US and imports/exports to other countries such as Canada, compound the need for effective surveillance and monitoring systems (Ball, 2002; Machado et al., 2019). Although cervid trade value chains include movement of whole live animals, semen, embryos, meat, trophies and other products (United States Department of Agriculture, 2019; Agriculture and Agri-Food Canada, 2019), we focus here on the potential for dissemination of CWD via movements of live farmed cervids. Understanding farm-to-farm contacts and networks through which farmed cervids move can help identify potential sources and transmission trends for CWD cases (Rorres et al., 2018), identify potential areas to target for cost-effective preventive interventions as well as monitoring and surveillance programs, as has been documented in wildlife (Silk et al., 2017) and other farmed animal species such as cattle and swine (VanderWaal et al., 2017; Kinsley et al., 2019). The objective of this study was to quantify movement patterns of farmed cervids in the state of Minnesota as a model for identifying potential disease mitigation points.
Figures
Fig. 1. Farm contacts network for cervid movements in Minnesota between 2013–2018 Farm contacts network for cervid movements in Minnesota between 2013–2018.
Fig. 2. Mean distribution of cervids moved in Minnesota monthly for the years 2013–2018 Mean distribution of cervids moved in Minnesota monthly for the years 2013–2018.
Fig. 3. (a & b):Choropleth map of cumulative in- and out degree for intrastate farmed… (a & b):Choropleth map of cumulative in- and out degree for intrastate farmed cervid movements in Minnesota between 2013–2018.
Fig. 4. (a & b):Choropleth map of farmed cervid interstate and international (import… (a & b):Choropleth map of farmed cervid interstate and international (import and export) movements for Minnesota between 2013–2018.
Section snippets
Data
Farmed cervid movement data were obtained for the period of 2013–2018 for the state of Minnesota, which represented the legal movements by farmed cervids in the state during that time. These data were based on movements reported to the Minnesota Board of Animal Health by cervid producers as required by Minnesota statutes. The data consisted of both international movements and movements within the U.S. The within-U.S. movements included intra-state movements and inter-state exports and imports
Results
Over the 6-year period, there were a total of 2578 movements of cervids to and from Minnesota farms. These movements involved a total of 11,298 cervids, with 6936 (61.4 %) white-tailed deer, 3742 (33.1 %) elk and 620 (5.5 %) other cervid species. Of these movements, 51.8 % were inter-state movements, i.e. 8.5 % imports (including 0.08 % from Canada) and 43.3 % exports. The remaining 48.2 % movements were intra-state movements (Table 2) between 432 farms. Intrastate movements involved movements
Discussion
In this study, network topology for intrastate farm contacts indicate that these networks are sparse (with low density and clustering) and dynamic through time. There is statistical evidence that contact between CWD-positive farms in this study population was not random and the outgoing infection chains for farms in this network could include up to 7 farms. Moreover, white-tailed deer were moved twice as much as elk and other species which may reflect cervid farm demographics and on-going
Conclusion
In conclusion, given that CWD transmission can occur through contact with infected body parts or through indirect contacts via contamination of feed and other fomites, understanding animal movements is critical for mitigating disease spread. Long distance commercial movements of cervids pose one risk for spread of CWD. This study approach can be used to understand disease transmission risks across the region and in North America in general.
Ethics statement
The authors confirm that the ethical policies of the journal, as noted on the journal’s authors guidelines page, have been adhered to and this study was done in accordance to the Research and Compliance Office Guidelines of the University of Minnesota.
Declaration of Competing Interest
The authors declare no financial or commercial conflicts of interest.
Acknowledgements
The authors acknowledge funding and access to cervid movement data from the Minnesota Board of Animal Health for this study.
References (45)
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***> 181 CWD-trace facilities associated with the CWD-positive deer breeding facilities in Hunt and Uvalde Counties, and some are out of state/country in Mexico
i finally got a recent copy of the CWD-trace facilities associated with the CWD-positive deer breeding facilities in Hunt and Uvalde Counties.
seems to date, there are 181 CWD-trace facilities associated with the CWD-positive deer breeding facilities in Hunt and Uvalde Counties, and some are out of state/country in Mexico. i was told that in the coming weeks, some of the facilities will start testing for cwd, and those results will be forthcoming later on. i hope they don't flounder on depopulation efforts if any positives are found. sad for Mexico (8 facilities).
Chronic Wasting Disease Discovered at Deer Breeding Facilities in Hunt and Uvalde Counties
March 31, 2021
WEDNESDAY, MARCH 31, 2021
Texas TPWD TAHC Chronic Wasting Disease Discovered at Deer Breeding Facilities in Hunt and Uvalde Counties
THURSDAY, MARCH 25, 2021
Texas CWD suspect positive results for a couple of deer breeding facilities
Texas Confirms CWD TSE Prion in 213 white-tailed deer, mule deer, red deer and elk to date, 148 connected to deer breeding facilities and release sites.
TUESDAY, MARCH 02, 2021
Texas Confirms CWD TSE Prion in 213 white-tailed deer, mule deer, red deer and elk to date, 148 connected to deer breeding facilities and release sites
TUESDAY, APRIL 13, 2021
Implications of farmed-cervid movements on the transmission of chronic wasting disease
MONDAY, MARCH 05, 2018
TRUCKING AROUND AND SPREADING CHRONIC WASTING DISEASE CWD TSE PRION VIA MOVEMENT OF CERVID AND TRANSPORTATION VEHICLES
FRIDAY, FEBRUARY 16, 2018
Wisconsin Stop private deer industry from trucking CWD across state
SATURDAY, JULY 09, 2016
Texas Intrastate – within state movement of all Cervid or Trucking Chronic Wasting Disease CWD TSE Prion Moratorium
Subject: Texas 85th Legislative Session 2017, bathroom politics, while Rome burns, CWD detected in 5th captive breeding facility
Subject: Texas 85th Legislative Session 2017, bathroom politics, while Rome burns, CWD detected in 5th captive breeding facility
thought i might comment on the bathroom politics in Austin, while Rome Burns...
Subject: Texas 85th Legislative Session 2017, bathroom politics, while Rome burns, CWD detected in 5th captive breeding facility
Subject: TEXAS CWD POLITICIANS, AND CORPORATE GREED
MONDAY, MAY 15, 2017
TEXAS New CWD TSE PRION Case Discovered at Fifth Captive Deer Breeding Facility
SUNDAY, MAY 14, 2017
85th Legislative Session 2017 AND THE TEXAS TWO STEP Chronic Wasting Disease CWD TSE Prion, and paying to play $$$
FRIDAY, OCTOBER 09, 2015
Texas TWA Chronic Wasting Disease TSE Prion Webinars and Meeting October 2015
http://chronic-wasting-disease.blogspot.com/2015/10/texas-twa-chronic-wasting-disease-tse.html
Thursday, August 20, 2015
*** TEXAS TAHC DEER BREEDER CWD PERMIT RULES EMERGENCY ADOPTION PREAMBLE ***
http://chronic-wasting-disease.blogspot.com/2015/08/texas-tahc-deer-breeder-cwd-permit.html
Under Texas law, though, breeder deer belong to the state, not the permittee. See, e.g., TEX. PARKS & WILD. CODE §§ 1.011 (“All wild animals . . . inside the borders of this state are the property of the people of this state.”); 43.364 (“All breeder deer . . . are under the full force of the laws of [Texas] pertaining to deer . . . .”). While a permittee may have possession of the breeder deer, the deer are only “held under a permit[.]” Id. § 43.351. Nowhere do the statutes or regulations state that breeder deer become the property of a permit holder.4 Regardless, even if they did give ownership of breeder deer to permit holders, the Andertons were not permit holders when the deer were killed.
http://www.ca5.uscourts.gov/opinions%5Cunpub%5C14/14-10297.0.pdf
While a permittee may have possession of the breeder deer, the deer are only “held under a permit[.]” Id. § 43.351
http://www.statutes.legis.state.tx.us/Docs/PW/htm/PW.43.htm
S.B. No. 820
http://www.legis.state.tx.us/tlodocs/83R/billtext/html/SB00820F.HTM
http://openstates.org/tx/bills/83/SB820/
Texas Senate Bill
Relating to the management, breeding, and destruction of deer and to procedures regarding certain deer permits.
View latest bill text Session:83rd Legislature (2013)
http://openstates.org/tx/bills/83/SB820/
Thursday, August 20, 2015
TEXAS CAPTIVE Deer Industry, Pens, Breeding, Big Business, Invites Crooks and CWD
http://chronic-wasting-disease.blogspot.com/2015/08/texas-captive-deer-industry-pens.html
Texas TWA Chronic Wasting Disease TSE Prion Webinars and Meeting October 2015
http://chronic-wasting-disease.blogspot.com/2015/10/texas-twa-chronic-wasting-disease-tse.html
Thursday, August 20, 2015
*** TEXAS TAHC DEER BREEDER CWD PERMIT RULES EMERGENCY ADOPTION PREAMBLE ***
http://chronic-wasting-disease.blogspot.com/2015/08/texas-tahc-deer-breeder-cwd-permit.html
Under Texas law, though, breeder deer belong to the state, not the permittee. See, e.g., TEX. PARKS & WILD. CODE §§ 1.011 (“All wild animals . . . inside the borders of this state are the property of the people of this state.”); 43.364 (“All breeder deer . . . are under the full force of the laws of [Texas] pertaining to deer . . . .”). While a permittee may have possession of the breeder deer, the deer are only “held under a permit[.]” Id. § 43.351. Nowhere do the statutes or regulations state that breeder deer become the property of a permit holder.4 Regardless, even if they did give ownership of breeder deer to permit holders, the Andertons were not permit holders when the deer were killed.
http://www.ca5.uscourts.gov/opinions%5Cunpub%5C14/14-10297.0.pdf
While a permittee may have possession of the breeder deer, the deer are only “held under a permit[.]” Id. § 43.351
http://www.statutes.legis.state.tx.us/Docs/PW/htm/PW.43.htm
S.B. No. 820
http://www.legis.state.tx.us/tlodocs/83R/billtext/html/SB00820F.HTM
http://openstates.org/tx/bills/83/SB820/
Texas Senate Bill
Relating to the management, breeding, and destruction of deer and to procedures regarding certain deer permits.
View latest bill text Session:83rd Legislature (2013)
http://openstates.org/tx/bills/83/SB820/
Thursday, August 20, 2015
TEXAS CAPTIVE Deer Industry, Pens, Breeding, Big Business, Invites Crooks and CWD
http://chronic-wasting-disease.blogspot.com/2015/08/texas-captive-deer-industry-pens.html
Thursday, August 20, 2015
*** TEXAS TAHC DEER BREEDER CWD PERMIT RULES EMERGENCY ADOPTION PREAMBLE ***
Wednesday, October 28, 2015
Texas' wild deer herd must be protected
Terry S. Singeltary Sr. Your opinions and comments have been submitted successfully. Thank you for participating in the TPWD regulatory process.
Wednesday, October 28, 2015
Interim Chronic Wasting Disease Response Rules Comment online through 07:00 a.m. November 5, 2015
SATURDAY, OCTOBER 03, 2015
TEXAS CHRONIC WASTING DISEASE CWD TSE PRION GOD MUST NOT BE A TEXAN 2002 TO 2015
TEXAS HISTORY OF CWD Singeltary telling TAHC, that CWD was waltzing into Texas from WSMR around Trans Pecos region, starting around 2001, 2002, and every year, there after, until New Mexico finally shamed TAHC et al to test where i had been telling them to test for a decade. 2012 cwd was detected first right there where i had been trying to tell TAHC for 10 years.
***> Singeltary on Texas Chronic Wasting Disease CWD TSE Prion History <***
SUNDAY, AUGUST 02, 2015
TEXAS CWD, Have you been ThunderStruck, deer semen, straw bred bucks, super ovulation, and the potential TSE Prion connection, what if?
Short Communications
Characterization of the prion protein gene in axis deer (Axis axis) and implications for susceptibility to chronic wasting disease
Matthew J. BuchholzORCID Icon,Emily A. Wright,Blake A. Grisham,Robert D. Bradley,Thomas L. Arsuffi &Warren C. Conway Pages 44-52 | Received 15 Jan 2021, Accepted 24 Mar 2021, Published online: 09 Apr 2021 Download citation https://doi.org/10.1080/19336896.2021.1910177 CrossMark LogoCrossMark In this article ABSTRACT Introduction Results Discussion Materials and Methods Acknowledgements Disclosure statement References Full Article Figures & data References Citations Metrics Licensing Reprints & Permissions PDF
ABSTRACT
Axis deer (Axis axis) occur both in captivity and free-ranging populations in portions of North America, but to-date, no data exist pertaining to the species’ susceptibility to CWD. We sequenced the prion protein gene (PRNP) from axis deer. We then compared axis deer PrPC sequences and amino acid polymorphisms to those of CWD susceptible species. A single PRNP allele with no evidence of intraspecies variation was identified in axis deer that indicates axis deer PRNP is most similar to North American elk (Cervus canadensis) PRNP. Therefore, axis deer may be susceptible to CWD. We recommend proactively increasing CWD surveillance for axis deer, particularly where CWD has been detected and axis deer are sympatric with native North American CWD susceptible species.
snip...
Axis deer were introduced to Texas in 1932 and following intentional emancipation and unintentional escape from confined ranches are now the most abundant free–ranging exotic cervid in Texas, and coexist with native cervid species. Regional biologists with Texas Parks and Wildlife Department (TPWD) speculate that the population is growing in both size and geographic distribution [21–23]. Self-sustaining, naturally reproducing, and free-ranging populations of axis deer exist in 3 of the 5 CWD surveillance zones established by TPWD as well as near or in CWD-positive captive deer facilities in Texas (Figure 1). Currently, no information exists pertaining to the risk of axis deer contracting and spreading CWD, and only 187 axis deer samples have been tested for CWD in Texas (all 187 have been negative). Comparatively, > 100,000 CWD tests have been administered to white-tailed deer and mule deer in Texas since 2012 [24]. Axis deer are legally classified as non-susceptible to CWD in Texas; however, the classification is based on the lack of a positive CWD test result, and not on an investigation into the biological susceptibility to infection with the CWD prion.
Figure 1. Reported county-level distribution of free-ranging axis deer (Axis axis) in Texas (a) and islands where free-range axis deer occur in Hawaii (b). The Texas map includes locations of the chronic wasting disease (CWD) surveillance zones established by Texas Parks and Wildlife Department (TPWD) in response to CWD having been detected in free-ranging and captive cervids
Results PRNP exon 3 (771 bp) was sequenced from 133 axis deer (88 from 16 Texas counties and 45 from 3 Hawaiian islands; Figure 2). A single genotype, lacking individual variation, was detected from all populations. Sequences from all 133 individuals have been submitted to the GenBank databases under accession numbers MT996365–MT996497.
Figure 2. Spatial distribution of the free-ranging axis deer (Axis axis) sequenced for PRNP exon 3 for this study and the reported ranges of free-ranging axis deer in Texas (a) and Hawaii (b)
snip...
There was a lack of continued support for differentiation of PRNP between known cervid sequences, including the sequence obtained for axis deer from this study. The lack of significant differentiation of PRNP within Cervidae supports that many, if not all, cervids potentially are susceptible to CWD, including axis deer, because their ensuing PrPC amino acid sequences likely do not have sufficient diversity to prevent misfolding [30], making them susceptible to CWD infection.
Definitive evidence such as a positive ELISA or IHC test or a protein misfolding cyclic amplification (PMCA) study of axis deer PrPC is needed to conclusively demonstrate axis deer are capable of contracting CWD. However, this research in combination with other work indicating a wider range of susceptible species than previously known [13,19], suggests axis deer in Texas and Hawaii may be susceptible to CWD, and should be managed as an at-risk species for CWD through the implementation of more formalized CWD surveillance. The proactive establishment of a CWD testing programme in axis deer wherever CWD has been detected in other species may be justified. Areas where axis deer coexist with native North American, CWD susceptible species, namely white-tailed deer, may also be justified. In Texas, coordinated CWD testing for axis deer might be important within previously established CWD surveillance and containment zones, followed by surveillance in areas where CWD may be a concern but not yet detected. Due to geographic isolation from areas where CWD occurs, axis deer populations in Hawaii are likely not high risk for CWD occurrence. However, awareness of the possibility and care should be taken to ensure CWD-infected material/animals does not arrive on the islands.
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.''
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.
SUNDAY, APRIL 14, 2019
Chronic Wasting Disease TSE Prion Strains everything in Texas is bigger, better, and badder 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
Wagner and Zabel have suggested a possible answer: Perhaps, they say, there is not just one chronic wasting disease, but rather a bunch of different strains of it. And those different strains could be emerging at different times across the globe.
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.”
SHOCKING ONES CONSCIENCE VIDEO
*** Danger of Canned Hunting Indiana Wildlife VIDEO ***
-----Original Message-----
From: Terry Singeltary <flounder9@verizon.net>
To: Terry Singeltary <flounder9@verizon.net>
Sent: Thu, Feb 25, 2021 2:14 pm
Subject: Texas AN ACT Sec. 43.370. relating to a deer breeding facility affected by chronic wasting disease H.B. 432
THURSDAY, FEBRUARY 25, 2021
From: Terry Singeltary <flounder9@verizon.net>
To: Terry Singeltary <flounder9@verizon.net>
Sent: Thu, Feb 25, 2021 2:14 pm
Subject: Texas AN ACT Sec. 43.370. relating to a deer breeding facility affected by chronic wasting disease H.B. 432
Greetings Honorable Legislators, Politicians, Lawmakers et al in Texas,
re-Texas AN ACT Sec. 43.370. relating to a deer breeding facility by chronic wasting disease H.B. 432
I urge you to read the science on chronic wasting disease tse prion aka mad cow type disease in cervid.
sometimes it takes a great length of time to test all cervid on a farm for cwd tse prion. sometimes even court proceedings go on for years, while an infected farmed cwd herd is incubating and spreading cwd, all the while those cervid look perfectly healthy, yet in the end, you have an infection rate as high as 79%, once the legal proceedings had ended, and depopulation finally took place (Iowa).
IF Texas continues to flounder with the CWD TSE Prion, and continue to cater to the game farms, velvet farms, sperm mills, horn mills, high/low fence shooting pens, we will end up like Wisconsin, Colorado, Pennsylvania, and these other states where cwd is out of control, and you will lose this fight with cwd, if not lost already. i have been trying to tell TAHC/TPWD et al this for decades. tried to tell the TAHC that cwd was waltzing across the border at the WSMR and New Mexico border around Trans Pecos region 10 years and every year there after, before they finally documented cwd...right exactly where i had pleaded with them 10+ years before to start testing.
i have followed the mad cow follies since hvCJD took my mother December 14, 1997, and you can't believe how terribly bad we failed and are still failing there. for Gods sake, we now know that cwd and scrapie will transmit to pigs by oral route, and NO ONE HAS CHANGED THE MAD COW FEED BAN 21 CFR PART 589.2001 to address these concerns. even DEFRA ET AL i.e. MAFF EU states concerns with this. (see below). we also know that cervid can get cwd by oral routes, and the mad cow feed ban does not pertain to cervid. it's voluntary and it's a terribly failed policy.
IF ANY cervid test positive for cwd tse prion, then that farm should be shut down, quarantined for at least 16 years, should be 21 years imo., science shows this...see;
***> 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
Gudmundur Georgsson1, Sigurdur Sigurdarson2, Paul Brown3
snip...see much more updated science on why this is a terrible idea for the great state of Texas...
Texas AN ACT Sec. 43.370. relating to a deer breeding facility affected by chronic wasting disease H.B. 432
2021 Transmissible Spongiform Encephalopathy TSE Prion End of Year Report 2020
CJD FOUNDATION VIRTUAL CONFERENCE CJD Foundation Research Grant Recipient Reports Panel 2 Nov 3, 2020
zoonotic potential of PMCA-adapted CWD PrP 96SS inoculum
4 different CWD strains, and these 4 strains have different potential to induce any folding of the human prion protein.
***> PIGS, WILD BOAR, CWD <***
***> POPULATIONS OF WILD BOARS IN THE UNITED STATES INCREASING SUPSTANTUALLY AND IN MANY AREAS WE CAN SEE A HIGH DENSITY OF WILD BOARS AND HIGH INCIDENT OF CHRONIC WASTING DISEASE
HYPOTHOSIS AND SPECIFIC AIMS
HYPOTHOSIS
BSE, SCRAPIE, AND CWD, EXPOSED DOMESTIC PIGS ACCUMULATE DIFFERENT QUANTITIES AND STRAINS OF PRIONS IN PERIPHERAL TISSUES, EACH ONE OF THEM WITH PARTICULAR ZOONOTIC POTENTIALS
Final Report – CJD Foundation Grant Program A.
Project Title: Systematic evaluation of the zoonotic potential of different CWD isolates. Principal Investigator: Rodrigo Morales, PhD.
Systematic evaluation of the zoonotic potential of different CWD isolates. Rodrigo Morales, PhD Assistant Professor Protein Misfolding Disorders lab Mitchell Center for Alzheimer’s disease and Related Brain Disorders Department of Neurology University of Texas Health Science Center at Houston Washington DC. July 14th, 2018
Conclusions and Future Directions • We have developed a highly sensitive and specific CWD-PMCA platform to be used as a diagnostic tool. • Current PMCA set up allow us to mimic relevant prion inter-species transmission events. • Polymorphic changes at position 96 of the prion protein apparently alter strain properties and, consequently, the zoonotic potential of CWD isolates. • Inter-species and inter-polymorphic PrPC → PrPSc conversions further increase the spectrum of CWD isolates possibly present in nature. • CWD prions generated in 96SS PrPC substrate apparently have greater inter-species transmission potentials. • Future experiments will explore the zoonotic potential of CWD prions along different adaptation scenarios, including inter-species and inter-polymorphic.
Research Project: TRANSMISSION, DIFFERENTIATION, AND PATHOBIOLOGY OF TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES Location: Virus and Prion Research
Title: Disease-associated prion protein detected in lymphoid tissues from pigs challenged with the agent of chronic wasting disease
Author item MOORE, SARAH - Orise Fellow item Kunkle, Robert item KONDRU, NAVEEN - Iowa State University item MANNE, SIREESHA - Iowa State University item SMITH, JODI - Iowa State University item KANTHASAMY, ANUMANTHA - Iowa State University item WEST GREENLEE, M - Iowa State University item Greenlee, Justin Submitted to: Prion Publication Type: Abstract Only Publication Acceptance Date: 3/15/2017 Publication Date: N/A Citation: N/A Interpretive Summary:
Technical Abstract: Aims: Chronic wasting disease (CWD) is a naturally-occurring, fatal neurodegenerative disease of cervids. We previously demonstrated that disease-associated prion protein (PrPSc) can be detected in the brain and retina from pigs challenged intracranially or orally with the CWD agent. In that study, neurological signs consistent with prion disease were observed only in one pig: an intracranially challenged pig that was euthanized at 64 months post-challenge. The purpose of this study was to use an antigen-capture immunoassay (EIA) and real-time quaking-induced conversion (QuIC) to determine whether PrPSc is present in lymphoid tissues from pigs challenged with the CWD agent.
Methods: At two months of age, crossbred pigs were challenged by the intracranial route (n=20), oral route (n=19), or were left unchallenged (n=9). At approximately 6 months of age, the time at which commercial pigs reach market weight, half of the pigs in each group were culled (<6 month challenge groups). The remaining pigs (>6 month challenge groups) were allowed to incubate for up to 73 months post challenge (mpc). The retropharyngeal lymph node (RPLN) was screened for the presence of PrPSc by EIA and immunohistochemistry (IHC). The RPLN, palatine tonsil, and mesenteric lymph node (MLN) from 6-7 pigs per challenge group were also tested using EIA and QuIC.
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.
Research Project: Pathobiology, Genetics, and Detection of Transmissible Spongiform Encephalopathies Location: Virus and Prion Research
Title: The agent of chronic wasting disease from pigs is infectious in transgenic mice expressing human PRNP
Author item MOORE, S - Orise Fellow item Kokemuller, Robyn item WEST-GREENLEE, M - Iowa State University item BALKEMA-BUSCHMANN, ANNE - Friedrich-Loeffler-institut item GROSCHUP, MARTIN - Friedrich-Loeffler-institut item Greenlee, Justin Submitted to: Prion Publication Type: Abstract Only Publication Acceptance Date: 5/10/2018 Publication Date: 5/22/2018 Citation: Moore, S.J., Kokemuller, R.D., West-Greenlee, M.H., Balkema-Buschmann, A., Groschup, M.H., Greenlee, J.J. 2018. The agent of chronic wasting disease from pigs is infectious in transgenic mice expressing human PRNP. Prion 2018, Santiago de Compostela, Spain, May 22-25, 2018. Paper No. WA15, page 44.
Interpretive Summary:
Technical Abstract: We have previously shown that the chronic wasting disease (CWD) agent from white-tailed deer can be transmitted to domestic pigs via intracranial or oral inoculation although with low attack rates and restricted PrPSc accumulation. The objective of this study was to assess the potential for cross-species transmission of pig-passaged CWD using bioassay in transgenic mice. Transgenic mice expressing human (Tg40), bovine (TgBovXV) or porcine (Tg002) PRNP were inoculated intracranially with 1% brain homogenate from a pig that had been intracranially inoculated with a pool of CWD from white-tailed deer. This pig developed neurological clinical signs, was euthanized at 64 months post-inoculation, and PrPSc was detected in the brain. Mice were monitored daily for clinical signs of disease until the end of the study. Mice were considered positive if PrPSc was detected in the brain using an enzyme immunoassay (EIA). In transgenic mice expressing porcine prion protein the average incubation period was 167 days post-inoculation (dpi) and 3/27 mice were EIA positive (attack rate = 11%). All 3 mice were found dead and clinical signs were not noted prior to death. One transgenic mouse expressing bovine prion protein was euthanized due to excessive scratching at 617 dpi and 2 mice culled at the end of the study at 700 dpi were EIA positive resulting in an overall attack rate of 3/16 (19%). None of the transgenic mice expressing human prion protein that died or were euthanized up to 769 dpi were EIA positive and at study end point at 800 dpi 2 mice had positive EIA results (overall attack rate = 2/20 = 10%). The EIA optical density (OD) readings for all positive mice were at the lower end of the reference range (positive mice range, OD = 0.266-0.438; test positive reference range, OD = 0.250-4.000). To the authors’ knowledge, cervid-derived CWD isolates have not been successfully transmitted to transgenic mice expressing human prion protein. The successful transmission of pig-passaged CWD to Tg40 mice reported here suggests that passage of the CWD agent through pigs results in a change of the transmission characteristics which reduces the transmission barrier of Tg40 mice to the CWD agent. If this biological behavior is recapitulated in the original host species, passage of the CWD agent through pigs could potentially lead to increased pathogenicity of the CWD agent in humans.
cwd scrapie pigs oral routes
***> 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.
America BSE 589.2001 FEED REGULATIONS, BSE SURVEILLANCE, BSE TESTING, and CJD TSE Prion
so far, we have been lucky. to date, with the science at hand, no cwd transmitted to cattle, that has been documented, TO DATE, WITH THE SCIENCE AT HAND, it's not to say it has not already happened, just like with zoonosis of cwd i.e. molecular transmission studies have shown that cwd transmission to humans would look like sporadic cjd, NOT nvCJD or what they call now vCJD. the other thing is virulence and or horizontal transmission. this is very concerning with the recent fact of what seems to be a large outbreak of a new tse prion disease in camels in Africa. there is much concern now with hay, straw, grains, and such, with the cwd tse prion endemic countries USA, Canada. what is of greatest concern is the different strains of cwd, and the virulence there from? this thing (cwd) keeps mutating to different strains, and to different species, the bigger the chance of one of these strains that WILL TRANSMIT TO CATTLE OR HUMANS, and that it is documented (i believe both has already occured imo with scienct to date). with that said, a few things to ponder, and i am still very concerned with, the animal feed. we now know from transmission studies that cwd and scrapie will transmit to pigs by oral routes. the atypical bse strains will transmit by oral routes. i don't mean to keep kicking a mad cow, just look at the science;
***> cattle, pigs, sheep, cwd, tse, prion, oh my!
***> In contrast, cattle are highly susceptible to white-tailed deer CWD and mule deer CWD in experimental conditions but no natural CWD infections in cattle have been reported (Sigurdson, 2008; Hamir et al., 2006).
Sheep and cattle may be exposed to CWD via common grazing areas with affected deer but so far, appear to be poorly susceptible to mule deer CWD (Sigurdson, 2008). In contrast, cattle are highly susceptible to white-tailed deer CWD and mule deer CWD in experimental conditions but no natural CWD infections in cattle have been reported (Sigurdson, 2008; Hamir et al., 2006). It is not known how susceptible humans are to CWD but given that the prion can be present in muscle, it is likely that humans have been exposed to the agent via consumption of venison (Sigurdson, 2008). Initial experimental research suggests that human susceptibility to CWD is low and there may be a robust species barrier for CWD transmission to humans (Sigurdson, 2008), however the risk appetite for a public health threat may still find this level unacceptable.
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.....
In the USA, under the Food and Drug Administration's BSE Feed Regulation (21 CFR 589.2000) most material (exceptions include milk, tallow, and gelatin) from deer and elk is prohibited for use in feed for ruminant animals. With regards to feed for non-ruminant animals, under FDA law, CWD positive deer may not be used for any animal feed or feed ingredients. For elk and deer considered at high risk for CWD, the FDA recommends that these animals do not enter the animal feed system. However, this recommendation is guidance and not a requirement by law. Animals considered at high risk for CWD include:
1) animals from areas declared to be endemic for CWD and/or to be CWD eradication zones and
2) deer and elk that at some time during the 60-month period prior to slaughter were in a captive herd that contained a CWD-positive animal.
Therefore, in the USA, materials from cervids other than CWD positive animals may be used in animal feed and feed ingredients for non-ruminants.
The amount of animal PAP that is of deer and/or elk origin imported from the USA to GB can not be determined, however, as it is not specified in TRACES.
It may constitute a small percentage of the 8412 kilos of non-fish origin processed animal proteins that were imported from US into GB in 2011.
Overall, therefore, it is considered there is a __greater than negligible risk___ that (nonruminant) animal feed and pet food containing deer and/or elk protein is imported into GB.
There is uncertainty associated with this estimate given the lack of data on the amount of deer and/or elk protein possibly being imported in these products.
snip.....
36% in 2007 (Almberg et al., 2011). In such areas, population declines of deer of up to 30 to 50% have been observed (Almberg et al., 2011). In areas of Colorado, the prevalence can be as high as 30% (EFSA, 2011). The clinical signs of CWD in affected adults are weight loss and behavioural changes that can span weeks or months (Williams, 2005). In addition, signs might include excessive salivation, behavioural alterations including a fixed stare and changes in interaction with other animals in the herd, and an altered stance (Williams, 2005). These signs are indistinguishable from cervids experimentally infected with bovine spongiform encephalopathy (BSE). Given this, if CWD was to be introduced into countries with BSE such as GB, for example, infected deer populations would need to be tested to differentiate if they were infected with CWD or BSE to minimise the risk of BSE entering the human food-chain via affected venison. 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.....
***> READ THIS VERY, VERY, CAREFULLY, AUGUST 1997 MAD COW FEED BAN WAS A SHAM, AS I HAVE STATED SINCE 1997! 3 FAILSAFES THE FDA ET AL PREACHED AS IF IT WERE THE GOSPEL, IN TERMS OF MAD COW BSE DISEASE IN USA, AND WHY IT IS/WAS/NOT A PROBLEM FOR THE USA, and those are;
BSE TESTING (failed terribly and proven to be a sham)
BSE SURVEILLANCE (failed terribly and proven to be a sham)
BSE 589.2001 FEED REGULATIONS (another colossal failure, and proven to be a sham)
these are facts folks. trump et al just admitted it with the feed ban.
see;
FDA Reports on VFD Compliance
John Maday
August 30, 2019 09:46 AM VFD-Form 007 (640x427)
Before and after the current Veterinary Feed Directive rules took full effect in January, 2017, the FDA focused primarily on education and outreach. ( John Maday ) Before and after the current Veterinary Feed Directive (VFD) rules took full effect in January, 2017, the FDA focused primarily on education and outreach to help feed mills, veterinarians and producers understand and comply with the requirements. Since then, FDA has gradually increased the number of VFD inspections and initiated enforcement actions when necessary. On August 29, FDA released its first report on inspection and compliance activities. The report, titled “Summary Assessment of Veterinary Feed Directive Compliance Activities Conducted in Fiscal Years 2016 – 2018,” is available online.
SUNDAY, SEPTEMBER 1, 2019
***> FDA Reports on VFD Compliance
TUESDAY, APRIL 18, 2017
*** EXTREME USA FDA PART 589 TSE PRION FEED LOOP HOLE STILL EXIST, AND PRICE OF POKER GOES UP ***
THURSDAY, SEPTEMBER 26, 2019
Veterinary Biologics Guideline 3.32E: Guideline for minimising the risk of introducing transmissible spongiform encephalopathy prions and other infectious agents through veterinary biologics
U.S.A. 50 STATE BSE MAD COW CONFERENCE CALL Jan. 9, 2001
Subject: BSE--U.S. 50 STATE CONFERENCE CALL Jan. 9, 2001
Date: Tue, 9 Jan 2001 16:49:00 -0800
From: "Terry S. Singeltary Sr."
Reply-To: Bovine Spongiform Encephalopathy
snip...
[host Richard Barns] and now a question from Terry S. Singeltary of CJD Watch.
[TSS] yes, thank you, U.S. cattle, what kind of guarantee can you give for serum or tissue donor herds?
[no answer, you could hear in the back ground, mumbling and 'we can't. have him ask the question again.]
[host Richard] could you repeat the question?
[TSS] U.S. cattle, what kind of guarantee can you give for serum or tissue donor herds?
[not sure whom ask this] what group are you with?
[TSS] CJD Watch, my Mom died from hvCJD and we are tracking CJD world-wide.
[not sure who is speaking] could you please disconnect Mr. Singeltary
[TSS] you are not going to answer my question?
[not sure whom speaking] NO
snip...see full archive and more of this;
3.2.1.2 Non‐cervid domestic species
The remarkably high rate of natural CWD transmission in the ongoing NA epidemics raises the question of the risk to livestock grazing on CWD‐contaminated shared rangeland and subsequently developing a novel CWD‐related prion disease. This issue has been investigated by transmitting CWD via experimental challenge to cattle, sheep and pigs and to tg mouse lines expressing the relevant species PrP.
For cattle challenged with CWD, PrPSc was detected in approximately 40% of intracerebrally inoculated animals (Hamir et al., 2005, 2006a, 2007). Tg mice expressing bovine PrP have also been challenged with CWD and while published studies have negative outcomes (Tamguney et al., 2009b), unpublished data provided for the purposes of this Opinion indicate that some transmission of individual isolates to bovinised mice is possible (Table 1).
In small ruminant recipients, a low rate of transmission was reported between 35 and 72 months post‐infection (mpi) in ARQ/ARQ and ARQ/VRQ sheep intracerebrally challenged with mule deer CWD (Hamir et al., 2006b), while two out of two ARQ/ARQ sheep intracerebrally inoculated with elk CWD developed clinical disease after 28 mpi (Madsen‐Bouterse et al., 2016). However, tg mice expressing ARQ sheep PrP were resistant (Tamguney et al., 2006) and tg mice expressing the VRQ PrP allele were poorly susceptible to clinical disease (Beringue et al., 2012; Madsen‐Bouterse et al., 2016). In contrast, tg mice expressing VRQ sheep PrP challenged with CWD have resulted in highly efficient, life‐long asymptomatic replication of these prions in the spleen tissue (Beringue et al., 2012).
A recent study investigated the potential for swine to serve as hosts of the CWD agent(s) by intracerebral or oral challenge of crossbred piglets (Moore et al., 2016b, 2017). Pigs sacrificed at 6 mpi, approximately the age at which pigs reach market weight, were clinically healthy and negative by diagnostic tests, although low‐level CWD agent replication could be detected in the CNS by bioassay in tg cervinised mice. Among pigs that were incubated for up to 73 mpi, some gave diagnostic evidence of CWD replication in the brain between 42 and 72 mpi. Importantly, this was observed also in one orally challenged pig at 64 mpi and the presence of low‐level CWD replication was confirmed by mouse bioassay. The authors of this study argued that pigs can support low‐level amplification of CWD prions, although the species barrier to CWD infection is relatively high and that the detection of infectivity in orally inoculated pigs with a mouse bioassay raises the possibility that naturally exposed pigs could act as a reservoir of CWD infectivity.
MONDAY, NOVEMBER 23, 2020
***> Chronic Wasting Disease CWD TSE Prion Cervid State by State and Global Update November 2020
FRIDAY, FEBRUARY 05, 2021
USA 50 STATE CWD TSE Prion UPDATE FEBRUARY 2021
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 with...
***> that’s what’s so worrisome about Iatrogenic mode of transmission, a simple autoclave will not kill this TSE prion agent.
1: J Neurol Neurosurg Psychiatry 1994 Jun;57(6):757-8
***> Transmission of Creutzfeldt-Jakob disease to a chimpanzee by electrodes contaminated during neurosurgery.
Gibbs CJ Jr, Asher DM, Kobrine A, Amyx HL, Sulima MP, Gajdusek DC.
Laboratory of Central Nervous System Studies, National Institute of
Neurological Disorders and Stroke, National Institutes of Health,
Bethesda, MD 20892.
Stereotactic multicontact electrodes used to probe the cerebral cortex of a middle aged woman with progressive dementia were previously implicated in the accidental transmission of Creutzfeldt-Jakob disease (CJD) to two younger patients. The diagnoses of CJD have been confirmed for all three cases. More than two years after their last use in humans, after three cleanings and repeated sterilisation in ethanol and formaldehyde vapour, the electrodes were implanted in the cortex of a chimpanzee. Eighteen months later the animal became ill with CJD. This finding serves to re-emphasise the potential danger posed by reuse of instruments contaminated with the agents of spongiform encephalopathies, even after scrupulous attempts to clean them.
PMID: 8006664 [PubMed - indexed for MEDLINE]
New studies on the heat resistance of hamster-adapted scrapie agent: Threshold survival after ashing at 600°C suggests an inorganic template of replication
Prion Infected Meat-and-Bone Meal Is Still Infectious after Biodiesel Production
MONDAY, APRIL 19, 2021
Evaluation of the application for new alternative biodiesel production process for rendered fat including Category 1 animal by-products (BDI-RepCat® process, AT)
Detection of protease-resistant cervid prion protein in water from a CWD-endemic area
A Quantitative Assessment of the Amount of Prion Diverted to Category 1 Materials and Wastewater During Processing
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
PPo4-4:
Survival and Limited Spread of TSE Infectivity after Burial
PPo4-4:
Survival and Limited Spread of TSE Infectivity after Burial
Karen Fernie, Allister Smith and Robert A. Somerville The Roslin Institute and R(D)SVS; University of Edinburgh; Roslin, Scotland UK
Scrapie and chronic wasting disease probably spread via environmental routes, and there are also concerns about BSE infection remaining in the environment after carcass burial or waste 3disposal. In two demonstration experiments we are determining survival and migration of TSE infectivity when buried for up to five years, as an uncontained point source or within bovine heads. Firstly boluses of TSE infected mouse brain were buried in lysimeters containing either sandy or clay soil. Migration from the boluses is being assessed from soil cores taken over time. With the exception of a very small amount of infectivity found 25 cm from the bolus in sandy soil after 12 months, no other infectivity has been detected up to three years. Secondly, ten bovine heads were spiked with TSE infected mouse brain and buried in the two soil types. Pairs of heads have been exhumed annually and assessed for infectivity within and around them. After one year and after two years, infectivity was detected in most intracranial samples and in some of the soil samples taken from immediately surrounding the heads. The infectivity assays for the samples in and around the heads exhumed at years three and four are underway. These data show that TSE infectivity can survive burial for long periods but migrates slowly. Risk assessments should take into account the likely long survival rate when infected material has been buried.
The authors gratefully acknowledge funding from DEFRA.
PRION CONFERENCE 2010 ABSTRACT REFERENCE
2018 - 2019
***> This is very likely to have parallels with control efforts for CWD in cervids.
Rapid recontamination of a farm building occurs after attempted prion removal
Kevin Christopher Gough, BSc (Hons), PhD1, Claire Alison Baker, BSc (Hons)2, Steve Hawkins, MIBiol3, Hugh Simmons, BVSc, MRCVS, MBA, MA3, Timm Konold, DrMedVet, PhD, MRCVS3 and Ben Charles Maddison, BSc (Hons), PhD2
Abstract
The transmissible spongiform encephalopathy scrapie of sheep/goats and chronic wasting disease of cervids are associated with environmental reservoirs of infectivity.
Preventing environmental prions acting as a source of infectivity to healthy animals is of major concern to farms that have had outbreaks of scrapie and also to the health management of wild and farmed cervids.
Here, an efficient scrapie decontamination protocol was applied to a farm with high levels of environmental contamination with the scrapie agent.
Post-decontamination, no prion material was detected within samples taken from the farm buildings as determined using a sensitive in vitro replication assay (sPMCA).
A bioassay consisting of 25 newborn lambs of highly susceptible prion protein genotype VRQ/VRQ introduced into this decontaminated barn was carried out in addition to sampling and analysis of dust samples that were collected during the bioassay.
Twenty-four of the animals examined by immunohistochemical analysis of lymphatic tissues were scrapie-positive during the bioassay, samples of dust collected within the barn were positive by month 3.
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...
As in the authors' previous study,12 the decontamination of this sheep barn was not effective at removing scrapie infectivity, and despite the extra measures brought into this study (more effective chemical treatment and removal of sources of dust) the overall rates of disease transmission mirror previous results on this farm. With such apparently effective decontamination (assuming that at least some sPMCA seeding ability is coincident with infectivity), how was infectivity able to persist within the environment and where does infectivity reside? Dust samples were collected in both the bioassay barn and also a barn subject to the same decontamination regime within the same farm (but remaining unoccupied). Within both of these barns dust had accumulated for three months that was able to seed sPMCA, indicating the accumulation of scrapie-containing material that was independent of the presence of sheep that may have been incubating and possibly shedding low amounts of infectivity.
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 scrapiepositive 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.
Acknowledgements The authors thank the APHA farm staff, Tony Duarte, Olly Roberts and Margaret Newlands for preparation of the sheep pens and animal husbandry during the study. The authors also thank the APHA pathology team for RAMALT and postmortem examination.
Funding This study was funded by DEFRA within project SE1865.
Competing interests None declared.
Saturday, January 5, 2019
Rapid recontamination of a farm building occurs after attempted prion removal
The effectiveness of on-farm decontamination methods for scrapie - SE1865
Description
Scrapie infectivity persists on farms where infected animals have been removed1. Recently we have demonstrated that it is possible to detect environmental scrapie contamination biochemically using serial Protein Misfolding Cyclic Amplification (sPMCA)2, allowing the monitoring of scrapie infectivity on farm premises. Ongoing Defra study SE1863 has compared pen decontamination regimes on a scrapie-infected farm by both sheep bioassay and sPMCA. For bioassay, scrapie-free genetically susceptible lambs were introduced into pens decontaminated using distinct methodologies, all pens contained scrapie-positive lambs within 1 year. Remarkably this included lambs housed within a pen which had been jet washed/chloros treated, followed by regalvanisation/ replacement of all metalwork and painting of all other surfaces.
We have recently demonstrated using sPMCA, that material collected on swabs from vertical surfaces at heights inaccessible to sheep within a barn on the same scrapie affected farm contained scrapie prions (unpublished observations). We hypothesise that scrapie prions are most likely to have been deposited in these areas by bioaerosol movement. We propose that this bioaerosol movement contributes to scrapie transmission within the barn, and could account for the sheep that became positive within the pen containing re-galvanised/new metalwork and repainted surfaces (project SE1863). It is proposed that a thorough decontamination that would minimise prion-contaminated dust, both within the building and its immediate vicinity, is likely to increase the effectiveness of current methods for decontaminating farm buildings following outbreaks of scrapie. The proposed study builds on our previous data and will thoroughly investigate the potential for farm building scrapie-contamination via the bioaerosol route, a previously unrecognised route for dissemination of scrapie infectivity. This route could lead to the direct infection of healthy animals and/or indirect transmission of disease via contamination of surfaces within animal pens. The proposed study would analyse material collected using air samplers set up within “scrapie-infected” barns and their immediate vicinity, to confirm that prion containing material can be airborne within a scrapie infected farm environment. The study would incorporate a biochemical assessment of different surface decontamination methods, in order to demonstrate the best methodology and then the analysis of air and surface samples after a complete building decontamination to remove sources of dust and surface bound prions from both the building and its immediate vicinity. Analysis of such surface and air samples collected before and after treatment would measure the reduction in levels of infectivity. It is envisaged that the biochemical demonstration of airborne prions and the effective reduction in such prion dissemination would lead to a sheep bioassay experiment that would be conducted after a full farm decontamination. This would fully assess the effectiveness of an optimised scrapie decontamination strategy.
This study will contribute directly to Defra policy on best practice for on-farm decontamination after outbreaks of scrapie; a situation particularly relevant to decontamination after scrapie cases on goat farms where no genetic resistance to scrapie has currently been identified, and where complete decontamination is essential in order to stop recurrence of scrapie after restocking.
Objective
Phase 1
• Determine the presence and relative levels of airborne prions on a scrapie infected farm.
• Evaluate different pen surface decontamination procedures.
Phase 2
• Determine the presence of any airborne prions in a barn after a full decontamination.
Phase 3
• Further assess the efficacy of the decontamination procedure investigated in phase 2 by sheep bioassay.
Time-Scale and Cost
From: 2012
To: 2016
Cost: £326,784
Contractor / Funded Organisations
A D A S UK Ltd (ADAS)
Keywords Animals Fields of Study Animal Health
The Effectiveness of on-Farm Decontamination Methods for Scrapie
Institutions ADAS
Start date 2012
End date 2016
Objective Phase 1
Determine the presence and relative levels of airborne prions on a scrapie infected farm. Evaluate different pen surface decontamination procedures.
Phase 2
Determine the presence of any airborne prions in a barn after a full decontamination.
Phase 3
Further assess the efficacy of the decontamination procedure investigated in phase 2 by sheep bioassay.
More information
Scrapie infectivity persists on farms where infected animals have been removed1. Recently we have demonstrated that it is possible to detect environmental scrapie contamination biochemically using serial Protein Misfolding Cyclic Amplification (sPMCA)2, allowing the monitoring of scrapie infectivity on farm premises. Ongoing Defra study SE1863 has compared pen decontamination regimes on a scrapie-infected farm by both sheep bioassay and sPMCA. For bioassay, scrapie-free genetically susceptible lambs were introduced into pens decontaminated using distinct methodologies, all pens contained scrapie-positive lambs within 1 year. Remarkably this included lambs housed within a pen which had been jet washed/chloros treated, followed by regalvanisation/replacement of all metalwork and painting of all other surfaces.
We have recently demonstrated using sPMCA, that material collected on swabs from vertical surfaces at heights inaccessible to sheep within a barn on the same scrapie affected farm contained scrapie prions (unpublished observations). We hypothesise that scrapie prions are most likely to have been deposited in these areas by bioaerosol movement. We propose that this bioaerosol movement contributes to scrapie transmission within the barn, and could account for the sheep that became positive within the pen containing re-galvanised/new metalwork and repainted surfaces (project SE1863). It is proposed that a thorough decontamination that would minimise prion-contaminated dust, both within the building and its immediate vicinity, is likely to increase the effectiveness of current methods for decontaminating farm buildings following outbreaks of scrapie. The proposed study builds on our previous data and will thoroughly investigate the potential for farm building scrapie contamination via the bioaerosol route, a previously unrecognised route for dissemination of scrapie infectivity. This route could lead to the direct infection of healthy animals and/or indirect transmission of disease via contamination of surfaces within animal pens. The proposed study would analyse material collected using air samplers set up within “scrapie-infected” barns and their immediate vicinity, to confirm that prion containing material can be airborne within a scrapie infected farm environment. The study would incorporate a biochemical assessment of different surface decontamination methods, in order to demonstrate the best methodology and then the analysis of air and surface samples after a complete building decontamination to remove sources of dust and surface bound prions from both the building and its immediate vicinity. Analysis of such surface and air samples collected before and after treatment would measure the reduction in levels of infectivity. It is envisaged that the biochemical demonstration of airborne prions and the effective reduction in such prion dissemination would lead to a sheep bioassay experiment that would be conducted after a full farm decontamination. This would fully assess the effectiveness of an optimised scrapie decontamination strategy.
This study will contribute directly to Defra policy on best practice for on-farm decontamination after outbreaks of scrapie; a situation particularly relevant to decontamination after scrapie cases on goat farms where no genetic resistance to scrapie has currently been identified, and where complete decontamination is essential in order to stop recurrence of scrapie after restocking.
Funding Source
Department for Environment, Food and Rural Affairs
Project source
View this project
Project number
SE1865
Categories
Foodborne Disease
Policy and Planning
Circulation of prions within dust on a scrapie affected farm
Kevin C Gough1 , Claire A Baker2 , Hugh A Simmons3 , Steve A Hawkins3 and Ben C Maddison2*
Abstract
Prion diseases are fatal neurological disorders that affect humans and animals. Scrapie of sheep/goats and Chronic Wasting Disease (CWD) of deer/elk are contagious prion diseases where environmental reservoirs have a direct link to the transmission of disease. Using protein misfolding cyclic amplification we demonstrate that scrapie PrPSc can be detected within circulating dusts that are present on a farm that is naturally contaminated with sheep scrapie. The presence of infectious scrapie within airborne dusts may represent a possible route of infection and illustrates the difficulties that may be associated with the effective decontamination of such scrapie affected premises.
snip...
Discussion We present biochemical data illustrating the airborne movement of scrapie containing material within a contaminated farm environment. We were able to detect scrapie PrPSc within extracts from dusts collected over a 70 day period, in the absence of any sheep activity. We were also able to detect scrapie PrPSc within dusts collected within pasture at 30 m but not at 60 m distance away from the scrapie contaminated buildings, suggesting that the chance of contamination of pasture by scrapie contaminated dusts decreases with distance from contaminated farm buildings. PrPSc amplification by sPMCA has been shown to correlate with infectivity and amplified products have been shown to be infectious [14,15]. These experiments illustrate the potential for low dose scrapie infectivity to be present within such samples. We estimate low ng levels of scrapie positive brain equivalent were deposited per m2 over 70 days, in a barn previously occupied by sheep affected with scrapie. This movement of dusts and the accumulation of low levels of scrapie infectivity within this environment may in part explain previous observations where despite stringent pen decontamination regimens healthy lambs still became scrapie infected after apparent exposure from their environment alone [16]. The presence of sPMCA seeding activity and by inference, infectious prions within dusts, and their potential for airborne dissemination is highly novel and may have implications for the spread of scrapie within infected premises. The low level circulation and accumulation of scrapie prion containing dust material within the farm environment will likely impede the efficient decontamination of such scrapie contaminated buildings unless all possible reservoirs of dust are removed. Scrapie containing dusts could possibly infect animals during feeding and drinking, and respiratory and conjunctival routes may also be involved. It has been demonstrated that scrapie can be efficiently transmitted via the nasal route in sheep [17], as is also the case for CWD in both murine models and in white tailed deer [18-20].
The sources of dust borne prions are unknown but it seems reasonable to assume that faecal, urine, skin, parturient material and saliva-derived prions may contribute to this mobile environmental reservoir of infectivity. This work highlights a possible transmission route for scrapie within the farm environment, and this is likely to be paralleled in CWD which shows strong similarities with scrapie in terms of prion dissemination and disease transmission. The data indicate that the presence of scrapie prions in dust is likely to make the control of these diseases a considerable challenge.
Research Project: TRANSMISSION, DIFFERENTIATION, AND PATHOBIOLOGY OF TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES Location: Virus and Prion Research
Title: Scrapie transmits to white-tailed deer by the oral route and has a molecular profile similar to chronic wasting disease
Author
item Greenlee, Justin item Moore, S - Orise Fellow item Smith, Jodi - Iowa State University item Kunkle, Robert item West Greenlee, M - Iowa State University Submitted to: American College of Veterinary Pathologists Meeting Publication Type: Abstract Only Publication Acceptance Date: 8/12/2015 Publication Date: N/A Citation: N/A
Interpretive Summary:
Technical Abstract: The purpose of this work was to determine susceptibility of white-tailed deer (WTD) to the agent of sheep scrapie and to compare the resultant PrPSc to that of the original inoculum and chronic wasting disease (CWD). We inoculated WTD by a natural route of exposure (concurrent oral and intranasal (IN); n=5) with a US scrapie isolate. All scrapie-inoculated deer had evidence of PrPSc accumulation. PrPSc was detected in lymphoid tissues at preclinical time points, and deer necropsied after 28 months post-inoculation had clinical signs, spongiform encephalopathy, and widespread distribution of PrPSc in neural and lymphoid tissues. Western blotting (WB) revealed PrPSc with 2 distinct molecular profiles. WB on cerebral cortex had a profile similar to the original scrapie inoculum, whereas WB of brainstem, cerebellum, or lymph nodes revealed PrPSc with a higher profile resembling CWD. Homogenates with the 2 distinct profiles from WTD with clinical scrapie were further passaged to mice expressing cervid prion protein and intranasally to sheep and WTD. In cervidized mice, the two inocula have distinct incubation times. Sheep inoculated intranasally with WTD derived scrapie developed disease, but only after inoculation with the inoculum that had a scrapie-like profile. The WTD study is ongoing, but deer in both inoculation groups are positive for PrPSc by rectal mucosal biopsy. In summary, this work demonstrates that WTD are susceptible to the agent of scrapie, two distinct molecular profiles of PrPSc are present in the tissues of affected deer, and inoculum of either profile readily passes to deer.
THURSDAY, FEBRUARY 28, 2019
BSE infectivity survives burial for five years with only limited spread
***> CONGRESSIONAL ABSTRACTS PRION CONFERENCE 2018
P69 Experimental transmission of CWD from white-tailed deer to co-housed reindeer
Mitchell G (1), Walther I (1), Staskevicius A (1), Soutyrine A (1), Balachandran A (1)
(1) National & OIE Reference Laboratory for Scrapie and CWD, Canadian Food Inspection Agency, Ottawa, Ontario, Canada.
Chronic wasting disease (CWD) continues to be detected in wild and farmed cervid populations of North America, affecting predominantly white-tailed deer, mule deer and elk. Extensive herds of wild caribou exist in northern regions of Canada, although surveillance has not detected the presence of CWD in this population. Oral experimental transmission has demonstrated that reindeer, a species closely related to caribou, are susceptible to CWD. Recently, CWD was detected for the first time in Europe, in wild Norwegian reindeer, advancing the possibility that caribou in North America could also become infected. Given the potential overlap in habitat between wild CWD-infected cervids and wild caribou herds in Canada, we sought to investigate the horizontal transmissibility of CWD from white-tailed deer to reindeer.
Two white-tailed deer were orally inoculated with a brain homogenate prepared from a farmed Canadian white-tailed deer previously diagnosed with CWD. Two reindeer, with no history of exposure to CWD, were housed in the same enclosure as the white-tailed deer, 3.5 months after the deer were orally inoculated. The white-tailed deer developed clinical signs consistent with CWD beginning at 15.2 and 21 months post-inoculation (mpi), and were euthanized at 18.7 and 23.1 mpi, respectively. Confirmatory testing by immunohistochemistry (IHC) and western blot demonstrated widespread aggregates of pathological prion protein (PrPCWD) in the central nervous system and lymphoid tissues of both inoculated white-tailed deer. Both reindeer were subjected to recto-anal mucosal associated lymphoid tissue (RAMALT) biopsy at 20 months post-exposure (mpe) to the white-tailed deer. The biopsy from one reindeer contained PrPCWD confirmed by IHC. This reindeer displayed only subtle clinical evidence of disease prior to a rapid decline in condition requiring euthanasia at 22.5 mpe. Analysis of tissues from this reindeer by IHC revealed widespread PrPCWD deposition, predominantly in central nervous system and lymphoreticular tissues. Western blot molecular profiles were similar between both orally inoculated white-tailed deer and the CWD positive reindeer. Despite sharing the same enclosure, the other reindeer was RAMALT negative at 20 mpe, and PrPCWD was not detected in brainstem and lymphoid tissues following necropsy at 35 mpe. Sequencing of the prion protein gene from both reindeer revealed differences at several codons, which may have influenced susceptibility to infection.
Natural transmission of CWD occurs relatively efficiently amongst cervids, supporting the expanding geographic distribution of disease and the potential for transmission to previously naive populations. The efficient horizontal transmission of CWD from white-tailed deer to reindeer observed here highlights the potential for reindeer to become infected if exposed to other cervids or environments infected with CWD.
SOURCE REFERENCE 2018 PRION CONFERENCE ABSTRACT
Research Project: TRANSMISSION, DIFFERENTIATION, AND PATHOBIOLOGY OF TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES Location: Virus and Prion Research
Title: Horizontal transmission of chronic wasting disease in reindeer
Author
item MOORE, SARAH - ORISE FELLOW item KUNKLE, ROBERT item WEST GREENLEE, MARY - IOWA STATE UNIVERSITY item Nicholson, Eric item RICHT, JUERGEN item HAMIR, AMIRALI item WATERS, WADE item Greenlee, Justin
Submitted to: Emerging Infectious Diseases
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/29/2016
Publication Date: 12/1/2016
Citation: Moore, S., Kunkle, R., Greenlee, M., Nicholson, E., Richt, J., Hamir, A., Waters, W., Greenlee, J. 2016. Horizontal transmission of chronic wasting disease in reindeer. Emerging Infectious Diseases. 22(12):2142-2145. doi:10.3201/eid2212.160635.
Interpretive Summary: Chronic wasting disease (CWD) is a fatal neurodegenerative disease that occurs in farmed and wild cervids (deer and elk) of North America and was recently diagnosed in a single free-ranging reindeer (Rangifer tarandus tarandus) in Norway. CWD is a transmissible spongiform encephalopathy (TSE) that is caused by infectious proteins called prions that are resistant to various methods of decontamination and environmental degradation. Little is known about the susceptibility of or potential for transmission amongst reindeer. In this experiment, we tested the susceptibility of reindeer to CWD from various sources (elk, mule deer, or white-tailed deer) after intracranial inoculation and tested the potential for infected reindeer to transmit to non-inoculated animals by co-housing or housing in adjacent pens. Reindeer were susceptible to CWD from elk, mule deer, or white-tailed deer sources after experimental inoculation. Most importantly, non-inoculated reindeer that were co-housed with infected reindeer or housed in pens adjacent to infected reindeer but without the potential for nose-to-nose contact also developed evidence of CWD infection. This is a major new finding that may have a great impact on the recently diagnosed case of CWD in the only remaining free-ranging reindeer population in Europe as our findings imply that horizontal transmission to other reindeer within that herd has already occurred. Further, this information will help regulatory and wildlife officials developing plans to reduce or eliminate CWD and cervid farmers that want to ensure that their herd remains CWD-free, but were previously unsure of the potential for reindeer to transmit CWD.
Technical Abstract: Chronic wasting disease (CWD) is a naturally-occurring, fatal prion disease of cervids. Reindeer (Rangifer tarandus tarandus) are susceptible to CWD following oral challenge, and CWD was recently reported in a free-ranging reindeer of Norway. Potential contact between CWD-affected cervids and Rangifer species that are free-ranging or co-housed on farms presents a potential risk of CWD transmission. The aims of this study were to 1) investigate the transmission of CWD from white-tailed deer (Odocoileus virginianus; CWDwtd), mule deer (Odocoileus hemionus; CWDmd), or elk (Cervus elaphus nelsoni; CWDelk) to reindeer via the intracranial route, and 2) to assess for direct and indirect horizontal transmission to non-inoculated sentinels. Three groups of 5 reindeer fawns were challenged intracranially with CWDwtd, CWDmd, or CWDelk. Two years after challenge of inoculated reindeer, non-inoculated negative control reindeer were introduced into the same pen as the CWDwtd inoculated reindeer (direct contact; n=4) or into a pen adjacent to the CWDmd inoculated reindeer (indirect contact; n=2). Experimentally inoculated reindeer were allowed to develop clinical disease. At death/euthanasia a complete necropsy examination was performed, including immunohistochemical testing of tissues for disease-associated CWD prion protein (PrPcwd). Intracranially challenged reindeer developed clinical disease from 21 months post-inoculation (months PI). PrPcwd was detected in 5 out of 6 sentinel reindeer although only 2 out of 6 developed clinical disease during the study period (< 57 months PI). We have shown that reindeer are susceptible to CWD from various cervid sources and can transmit CWD to naïve reindeer both directly and indirectly.
***> 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
Gudmundur Georgsson1, Sigurdur Sigurdarson2, Paul Brown3
First Published: 01 December 2006 https://doi.org/10.1099/vir.0.82011-0 ABSTRACT In 1978, a rigorous programme was implemented to stop the spread of, and subsequently eradicate, sheep scrapie in Iceland. Affected flocks were culled, premises were disinfected and, after 2–3 years, restocked with lambs from scrapie-free areas. Between 1978 and 2004, scrapie recurred on 33 farms. 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. Of special interest was one farm with a small, completely self-contained flock where scrapie recurred 18 years after culling, 2 years after some lambs had been housed in an old sheep-house that had never been disinfected. Epidemiological investigation established with near certitude that the disease had not been introduced from the outside and it is concluded that the agent may have persisted in the old sheep-house for at least 16 years.
Gudmundur Georgsson,1 Sigurdur Sigurdarson2 and Paul Brown3
Correspondence
Gudmundur Georgsson ggeorgs@hi.is
1 Institute for Experimental Pathology, University of Iceland, Keldur v/vesturlandsveg, IS-112 Reykjavı´k, Iceland
2 Laboratory of the Chief Veterinary Officer, Keldur, Iceland
3 Bethesda, Maryland, USA
Received 7 March 2006 Accepted 6 August 2006
In 1978, a rigorous programme was implemented to stop the spread of, and subsequently eradicate, sheep scrapie in Iceland. Affected flocks were culled, premises were disinfected and, after 2–3 years, restocked with lambs from scrapie-free areas. Between 1978 and 2004, scrapie recurred on 33 farms. 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. Of special interest was one farm with a small, completely self-contained flock where scrapie recurred 18 years after culling, 2 years after some lambs had been housed in an old sheephouse that had never been disinfected. Epidemiological investigation established with near certitude that the disease had not been introduced from the outside and it is concluded that the agent may have persisted in the old sheep-house for at least 16 years.
TITLE: PATHOLOGICAL FEATURES OF CHRONIC WASTING DISEASE IN REINDEER AND DEMONSTRATION OF HORIZONTAL TRANSMISSION
*** DECEMBER 2016 CDC EMERGING INFECTIOUS DISEASE JOURNAL CWD HORIZONTAL TRANSMISSION
SEE;
Back around 2000, 2001, or so, I was corresponding with officials abroad during the bse inquiry, passing info back and forth, 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” I never knew who they were, but I never forgot;
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
Infectivity surviving ashing to 600*C is (in my opinion) degradable but infective. based on Bown & Gajdusek, (1991), landfill and burial may be assumed to have a reduction factor of 98% (i.e. a factor of 50) over 3 years. CJD-infected brain-tissue remained infectious after storing at room-temperature for 22 months (Tateishi et al, 1988). Scrapie agent is known to remain viable after at least 30 months of desiccation (Wilson et al, 1950). and pastures that had been grazed by scrapie-infected sheep still appeared to be contaminated with scrapie agent three years after they were last occupied by sheep (Palsson, 1979).
Dr. Paul Brown Scrapie Soil Test BSE Inquiry Document
Using in vitro Prion replication for high sensitive detection of prions and prionlike proteins and for understanding mechanisms of transmission.
Claudio Soto Mitchell Center for Alzheimer's diseases and related Brain disorders, Department of Neurology, University of Texas Medical School at Houston.
Prion and prion-like proteins are misfolded protein aggregates with the ability to selfpropagate to spread disease between cells, organs and in some cases across individuals. I n T r a n s m i s s i b l e s p o n g i f o r m encephalopathies (TSEs), prions are mostly composed by a misfolded form of the prion protein (PrPSc), which propagates by transmitting its misfolding to the normal prion protein (PrPC). The availability of a procedure to replicate prions in the laboratory may be important to study the mechanism of prion and prion-like spreading and to develop high sensitive detection of small quantities of misfolded proteins in biological fluids, tissues and environmental samples. Protein Misfolding Cyclic Amplification (PMCA) is a simple, fast and efficient methodology to mimic prion replication in the test tube. PMCA is a platform technology that may enable amplification of any prion-like misfolded protein aggregating through a seeding/nucleation process. In TSEs, PMCA is able to detect the equivalent of one single molecule of infectious PrPSc and propagate prions that maintain high infectivity, strain properties and species specificity. Using PMCA we have been able to detect PrPSc in blood and urine of experimentally infected animals and humans affected by vCJD with high sensitivity and specificity. Recently, we have expanded the principles of PMCA to amplify amyloid-beta (Aβ) and alphasynuclein (α-syn) aggregates implicated in Alzheimer's and Parkinson's diseases, respectively. Experiments are ongoing to study the utility of this technology to detect Aβ and α-syn aggregates in samples of CSF and blood from patients affected by these diseases.
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***>>> Recently, we have been using PMCA to study the role of environmental prion contamination on the horizontal spreading of TSEs. These experiments have focused on the study of the interaction of prions with plants and environmentally relevant surfaces. Our results show that plants (both leaves and roots) bind tightly to prions present in brain extracts and excreta (urine and feces) and retain even small quantities of PrPSc for long periods of time. Strikingly, ingestion of prioncontaminated leaves and roots produced disease with a 100% attack rate and an incubation period not substantially longer than feeding animals directly with scrapie brain homogenate. Furthermore, plants can uptake prions from contaminated soil and transport them to different parts of the plant tissue (stem and leaves). Similarly, prions bind tightly to a variety of environmentally relevant surfaces, including stones, wood, metals, plastic, glass, cement, etc. Prion contaminated surfaces efficiently transmit prion disease when these materials were directly injected into the brain of animals and strikingly when the contaminated surfaces were just placed in the animal cage. These findings demonstrate that environmental materials can efficiently bind infectious prions and act as carriers of infectivity, suggesting that they may play an important role in the horizontal transmission of the disease.
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Since its invention 13 years ago, PMCA has helped to answer fundamental questions of prion propagation and has broad applications in research areas including the food industry, blood bank safety and human and veterinary disease diagnosis.
source reference Prion Conference 2015 abstract book
Grass Plants Bind, Retain, Uptake, and Transport Infectious Prions
Sandra Pritzkow,1 Rodrigo Morales,1 Fabio Moda,1,3 Uffaf Khan,1 Glenn C. Telling,2 Edward Hoover,2 and Claudio Soto1, * 1Mitchell Center for Alzheimer’s Disease and Related Brain Disorders, Department of Neurology, University of Texas Medical School at Houston, 6431 Fannin Street, Houston, TX 77030, USA
2Prion Research Center, Department of Microbiology, Immunology, and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USA
3Present address: IRCCS Foundation Carlo Besta Neurological Institute, 20133 Milan, Italy *Correspondence: claudio.soto@uth.tmc.edu http://dx.doi.org/10.1016/j.celrep.2015.04.036
SUMMARY
Prions are the protein-based infectious agents responsible for prion diseases. Environmental prion contamination has been implicated in disease transmission. Here, we analyzed the binding and retention of infectious prion protein (PrPSc) to plants. Small quantities of PrPSc contained in diluted brain homogenate or in excretory materials (urine and feces) can bind to wheat grass roots and leaves. Wild-type hamsters were efficiently infected by ingestion of prion-contaminated plants. The prion-plant interaction occurs with prions from diverse origins, including chronic wasting disease. Furthermore, leaves contaminated by spraying with a prion-containing preparation retained PrPSc for several weeks in the living plant. Finally, plants can uptake prions from contaminated soil and transport them to aerial parts of the plant (stem and leaves). These findings demonstrate that plants can efficiently bind infectious prions and act as carriers of infectivity, suggesting a possible role of environmental prion contamination in the horizontal transmission of the disease.
INTRODUCTION
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DISCUSSION
This study shows that plants can efficiently bind prions contained in brain extracts from diverse prion infected animals, including CWD-affected cervids. PrPSc attached to leaves and roots from wheat grass plants remains capable of seeding prion replication in vitro. Surprisingly, the small quantity of PrPSc naturally excreted in urine and feces from sick hamster or cervids was enough to efficiently contaminate plant tissue. Indeed, our results suggest that the majority of excreted PrPSc is efficiently captured by plants’ leaves and roots. Moreover, leaves can be contaminated by spraying them with a prion-containing extract, and PrPSc remains detectable in living plants for as long as the study was performed (several weeks). Remarkably, prion contaminated plants transmit prion disease to animals upon ingestion, producing a 100% attack rate and incubation periods not substantially longer than direct oral administration of sick brain homogenates.
Finally, an unexpected but exciting result was that plants were able to uptake prions from contaminated soil and transport them to aerial parts of the plant tissue. Although it may seem farfetched that plants can uptake proteins from the soil and transport it to the parts above the ground, there are already published reports of this phenomenon (McLaren et al., 1960; Jensen and McLaren, 1960;Paungfoo-Lonhienne et al., 2008). The high resistance of prions to degradation and their ability to efficiently cross biological barriers may play a role in this process. The mechanism by which plants bind, retain, uptake, and transport prions is unknown. We are currently studying the way in which prions interact with plants using purified, radioactively labeled PrPSc to determine specificity of the interaction, association constant, reversibility, saturation, movement, etc.
Epidemiological studies have shown numerous instances of scrapie or CWD recurrence upon reintroduction of animals on pastures previously exposed to prion-infected animals. Indeed, reappearance of scrapie has been documented following fallow periods of up to 16 years (Georgsson et al., 2006), and pastures were shown to retain infectious CWD prions for at least 2 years after exposure (Miller et al., 2004). It is likely that the environmentally mediated transmission of prion diseases depends upon the interaction of prions with diverse elements, including soil, water, environmental surfaces, various invertebrate animals, and plants.
However, since plants are such an important component of the environment and also a major source of food for many animal species, including humans, our results may have far-reaching implications for animal and human health. Currently, the perception of the riskfor animal-to-human prion transmission has beenmostly limited to consumption or exposure to contaminated meat; our results indicate that plants might also be an important vector of transmission that needs to be considered in risk assessment.
RIGINAL RESEARCH ARTICLE
Front. Vet. Sci., 14 September 2015 | https://doi.org/10.3389/fvets.2015.00032
Objects in contact with classical scrapie sheep act as a reservoir for scrapie transmission
imageTimm Konold1*, imageStephen A. C. Hawkins2, imageLisa C. Thurston3, imageBen C. Maddison4, imageKevin C. Gough5, imageAnthony Duarte1 and imageHugh A. Simmons1
1Animal Sciences Unit, Animal and Plant Health Agency Weybridge, Addlestone, UK
2Pathology Department, Animal and Plant Health Agency Weybridge, Addlestone, UK
3Surveillance and Laboratory Services, Animal and Plant Health Agency Penrith, Penrith, UK
4ADAS UK, School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington, UK
5School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington, UK
Classical scrapie is an environmentally transmissible prion disease of sheep and goats. Prions can persist and remain potentially infectious in the environment for many years and thus pose a risk of infecting animals after re-stocking. In vitro studies using serial protein misfolding cyclic amplification (sPMCA) have suggested that objects on a scrapie-affected sheep farm could contribute to disease transmission. This in vivo study aimed to determine the role of field furniture (water troughs, feeding troughs, fencing, and other objects that sheep may rub against) used by a scrapie-infected sheep flock as a vector for disease transmission to scrapie-free lambs with the prion protein genotype VRQ/VRQ, which is associated with high susceptibility to classical scrapie. When the field furniture was placed in clean accommodation, sheep became infected when exposed to either a water trough (four out of five) or to objects used for rubbing (four out of seven). This field furniture had been used by the scrapie-infected flock 8 weeks earlier and had previously been shown to harbor scrapie prions by sPMCA. Sheep also became infected (20 out of 23) through exposure to contaminated field furniture placed within pasture not used by scrapie-infected sheep for 40 months, even though swabs from this furniture tested negative by PMCA. This infection rate decreased (1 out of 12) on the same paddock after replacement with clean field furniture. Twelve grazing sheep exposed to field furniture not in contact with scrapie-infected sheep for 18 months remained scrapie free. The findings of this study highlight the role of field furniture used by scrapie-infected sheep to act as a reservoir for disease re-introduction although infectivity declines considerably if the field furniture has not been in contact with scrapie-infected sheep for several months. PMCA may not be as sensitive as VRQ/VRQ sheep to test for environmental contamination.
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Discussion
Classical scrapie is an environmentally transmissible disease because it has been reported in naïve, supposedly previously unexposed sheep placed in pastures formerly occupied by scrapie-infected sheep (4, 19, 20).
Although the vector for disease transmission is not known, soil is likely to be an important reservoir for prions (2) where – based on studies in rodents – prions can adhere to minerals as a biologically active form (21) and remain infectious for more than 2 years (22).
Similarly, chronic wasting disease (CWD) has re-occurred in mule deer housed in paddocks used by infected deer 2 years earlier, which was assumed to be through foraging and soil consumption (23).
Our study suggested that the risk of acquiring scrapie infection was greater through exposure to contaminated wooden, plastic, and metal surfaces via water or food troughs, fencing, and hurdles than through grazing.
Drinking from a water trough used by the scrapie flock was sufficient to cause infection in sheep in a clean building.
Exposure to fences and other objects used for rubbing also led to infection, which supported the hypothesis that skin may be a vector for disease transmission (9).
The risk of these objects to cause infection was further demonstrated when 87% of 23 sheep presented with PrPSc in lymphoid tissue after grazing on one of the paddocks, which contained metal hurdles, a metal lamb creep and a water trough in contact with the scrapie flock up to 8 weeks earlier, whereas no infection had been demonstrated previously in sheep grazing on this paddock, when equipped with new fencing and field furniture.
When the contaminated furniture and fencing were removed, the infection rate dropped significantly to 8% of 12 sheep, with soil of the paddock as the most likely source of infection caused by shedding of prions from the scrapie-infected sheep in this paddock up to a week earlier.
This study also indicated that the level of contamination of field furniture sufficient to cause infection was dependent on two factors: stage of incubation period and time of last use by scrapie-infected sheep.
Drinking from a water trough that had been used by scrapie sheep in the predominantly pre-clinical phase did not appear to cause infection, whereas infection was shown in sheep drinking from the water trough used by scrapie sheep in the later stage of the disease.
It is possible that contamination occurred through shedding of prions in saliva, which may have contaminated the surface of the water trough and subsequently the water when it was refilled.
Contamination appeared to be sufficient to cause infection only if the trough was in contact with sheep that included clinical cases.
Indeed, there is an increased risk of bodily fluid infectivity with disease progression in scrapie (24) and CWD (25) based on PrPSc detection by sPMCA.
Although ultraviolet light and heat under natural conditions do not inactivate prions (26), furniture in contact with the scrapie flock, which was assumed to be sufficiently contaminated to cause infection, did not act as vector for disease if not used for 18 months, which suggest that the weathering process alone was sufficient to inactivate prions.
PrPSc detection by sPMCA is increasingly used as a surrogate for infectivity measurements by bioassay in sheep or mice.
In this reported study, however, the levels of PrPSc present in the environment were below the limit of detection of the sPMCA method, yet were still sufficient to cause infection of in-contact animals.
In the present study, the outdoor objects were removed from the infected flock 8 weeks prior to sampling and were positive by sPMCA at very low levels (2 out of 37 reactions).
As this sPMCA assay also yielded 2 positive reactions out of 139 in samples from the scrapie-free farm, the sPMCA assay could not detect PrPSc on any of the objects above the background of the assay.
False positive reactions with sPMCA at a low frequency associated with de novo formation of infectious prions have been reported (27, 28).
This is in contrast to our previous study where we demonstrated that outdoor objects that had been in contact with the scrapie-infected flock up to 20 days prior to sampling harbored PrPSc that was detectable by sPMCA analysis [4 out of 15 reactions (12)] and was significantly more positive by the assay compared to analogous samples from the scrapie-free farm.
This discrepancy could be due to the use of a different sPMCA substrate between the studies that may alter the efficiency of amplification of the environmental PrPSc.
In addition, the present study had a longer timeframe between the objects being in contact with the infected flock and sampling, which may affect the levels of extractable PrPSc.
Alternatively, there may be potentially patchy contamination of this furniture with PrPSc, which may have been missed by swabbing.
The failure of sPMCA to detect CWD-associated PrP in saliva from clinically affected deer despite confirmation of infectivity in saliva-inoculated transgenic mice was associated with as yet unidentified inhibitors in saliva (29), and it is possible that the sensitivity of sPMCA is affected by other substances in the tested material.
In addition, sampling of amplifiable PrPSc and subsequent detection by sPMCA may be more difficult from furniture exposed to weather, which is supported by the observation that PrPSc was detected by sPMCA more frequently in indoor than outdoor furniture (12).
A recent experimental study has demonstrated that repeated cycles of drying and wetting of prion-contaminated soil, equivalent to what is expected under natural weathering conditions, could reduce PMCA amplification efficiency and extend the incubation period in hamsters inoculated with soil samples (30).
This seems to apply also to this study even though the reduction in infectivity was more dramatic in the sPMCA assays than in the sheep model.
Sheep were not kept until clinical end-point, which would have enabled us to compare incubation periods, but the lack of infection in sheep exposed to furniture that had not been in contact with scrapie sheep for a longer time period supports the hypothesis that prion degradation and subsequent loss of infectivity occurs even under natural conditions.
In conclusion, the results in the current study indicate that removal of furniture that had been in contact with scrapie-infected animals should be recommended, particularly since cleaning and decontamination may not effectively remove scrapie infectivity (31), even though infectivity declines considerably if the pasture and the field furniture have not been in contact with scrapie-infected sheep for several months. As sPMCA failed to detect PrPSc in furniture that was subjected to weathering, even though exposure led to infection in sheep, this method may not always be reliable in predicting the risk of scrapie infection through environmental contamination.
These results suggest that the VRQ/VRQ sheep model may be more sensitive than sPMCA for the detection of environmentally associated scrapie, and suggest that extremely low levels of scrapie contamination are able to cause infection in susceptible sheep genotypes.
Keywords: classical scrapie, prion, transmissible spongiform encephalopathy, sheep, field furniture, reservoir, serial protein misfolding cyclic amplification
Chemical Inactivation of Prions Is Altered by Binding to the Soil Mineral Montmorillonite
Clarissa J. Booth, Stuart Siegfried Lichtenberg, Richard J. Chappell, and Joel A. Pedersen* Cite this: ACS Infect. Dis. 2021, XXXX, XXX, XXX-XXX Publication Date:March 31, 2021 https://doi.org/10.1021/acsinfecdis.0c00860 © 2021 American Chemical Society
Abstract
Environmental routes of transmission contribute to the spread of the prion diseases chronic wasting disease of deer and elk and scrapie of sheep and goats. Prions can persist in soils and other environmental matrices and remain infectious for years. Prions bind avidly to the common soil mineral montmorillonite, and such binding can dramatically increase oral disease transmission. Decontamination of soil in captive facilities and natural habitats requires inactivation agents that are effective when prions are bound to soil microparticles. Here, we investigate the inactivation of free and montmorillonite-bound prions with sodium hydroxide, acidic pH, Environ LpH, and sodium hypochlorite. Immunoblotting and bioassays confirm that sodium hydroxide and sodium hypochlorite are effective for prion deactivation, although montmorillonite appears to reduce the efficacy of hypochlorite. Acidic conditions slightly reduce prion infectivity, and the acidic phenolic disinfectant Environ LpH produces slight reductions in infectivity and immunoreactivity. The extent to which the association with montmorillonite protects prions from chemical inactivation appears influenced by the effect of chemical agents on the clay structure and surface pH. When clay morphology remains relatively unaltered, as when exposed to hypochlorite, montmorillonite-bound prions appear to be protected from inactivation. In contrast, when the clay structure is substantially transformed, as when exposed to high concentrations of sodium hydroxide, the attachment to montmorillonite does not slow degradation. A reduction in surface pH appears to cause slight disruptions in clay structure, which enhances degradation under these conditions. We expect our findings will aid the development of remediation approaches for successful decontamination of prion-contaminated sites.
Front. Vet. Sci., 04 March 2021 | https://doi.org/10.3389/fvets.2021.643754
Real-Time Quaking-Induced Conversion Detection of PrPSc in Fecal Samples From Chronic Wasting Disease Infected White-Tailed Deer Using Bank Vole Substrate
Soyoun Hwang, Justin J. Greenlee and Eric M. Nicholson*
Virus and Prion Research Unit, National Animal Disease Center, United States Department of Agriculture, Agricultural Research Service, Ames, IA, United States
Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy (TSE) that is fatal to free-range and captive cervids. CWD has been reported in the United States, Canada, South Korea, Norway, Finland, and Sweden, and the case numbers in both wild and farmed cervids are increasing rapidly. Studies indicate that lateral transmission of cervids likely occurs through the shedding of infectious prions in saliva, feces, urine, and blood into the environment. Therefore, the detection of CWD early in the incubation time is advantageous for disease management. In this study, we adapt real-time quacking-induced conversion (RT-QuIC) assays to detect the seeding activity of CWD prions in feces samples from clinical and preclinical white-tailed deer. By optimizing reaction conditions for temperature as well as the salt and salt concentration, prion seeding activity from both clinical and preclinical animals were detected by RT-QuIC. More specifically, all fecal samples collected from 6 to 30 months post inoculation showed seeding activity under the conditions of study. The combination of a highly sensitive detection tool paired with a sample type that may be collected non-invasively allows a useful tool to support CWD surveillance in wild and captive cervids.
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Altogether, we confirm again that RT-QuIC is a powerful tool to detect infectious fecal prions from CWD infected white-tailed deer. Use of feces is a non-invasive and non-stressing approach to sampling of animals, of particular importance for non-domesticated animals that may be less tolerant to the handling required for sampling by other means. This is of importance to the management of both wild and farmed cervids and is also of use in experimental settings where repeated sampling of an individual animal would be otherwise difficult. Ultimately, fecal sampling may prove useful in the determination of disease prevalence in a geographic region or within a herd.
Chronic Wasting Disease CWD TSE Prion Zoonosis Zoonotic Update
Cervid to human prion transmission
Kong, Qingzhong
Case Western Reserve University, Cleveland, OH, United States
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.
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.
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 tranmission 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 freeranging 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 freeranging 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:
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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.
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Source Prion Conference 2018 Abstracts
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.
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
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.
SATURDAY, FEBRUARY 23, 2019
Chronic Wasting Disease CWD TSE Prion and THE FEAST 2003 CDC an updated review of the science 2019
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. "
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....
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.
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.
*** 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
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 ;
> 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 https://www.ncbi.nlm.nih.gov/pubmed/?term=sporadic
spontaneous = 325,650 hits https://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).***
CWD TSE PRION AND ZOONOTIC, ZOONOSIS, POTENTIAL
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: <3daf5023 .4080804="" wt.net="">
Dear Terry,
An excellent piece of review as this literature is desparately 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 ===============
''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 ;
http://web.archive.org/web/20090506050043/http://www.bseinquiry.gov.uk/files/yb/1994/08/00004001.pdf
http://web.archive.org/web/20090506050244/http://www.bseinquiry.gov.uk/files/yb/1994/07/00001001.pdf
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
***> ''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) <***
***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.
https://www.nature.com/articles/srep11573
O.05: Transmission of prions to primates after extended silent incubation periods: Implications for BSE and scrapie risk assessment in human populations
Emmanuel Comoy, Jacqueline Mikol, Valerie Durand, Sophie Luccantoni, Evelyne Correia, Nathalie Lescoutra, Capucine Dehen, and Jean-Philippe Deslys Atomic Energy Commission; Fontenay-aux-Roses, France
Prion diseases (PD) are the unique neurodegenerative proteinopathies reputed to be transmissible under field conditions since decades. The transmission of Bovine Spongiform Encephalopathy (BSE) to humans evidenced that an animal PD might be zoonotic under appropriate conditions. Contrarily, in the absence of obvious (epidemiological or experimental) elements supporting a transmission or genetic predispositions, PD, like the other proteinopathies, are reputed to occur spontaneously (atpical animal prion strains, sporadic CJD summing 80% of human prion cases).
Non-human primate models provided the first evidences supporting the transmissibiity of human prion strains and the zoonotic potential of BSE. Among them, cynomolgus macaques brought major information for BSE risk assessment for human health (Chen, 2014), according to their phylogenetic proximity to humans and extended lifetime. We used this model to assess the zoonotic potential of other animal PD from bovine, ovine and cervid origins even after very long silent incubation periods.
*** We recently observed the direct transmission of a natural classical scrapie isolate to macaque after a 10-year silent incubation period,
***with features similar to some reported for human cases of sporadic CJD, albeit requiring fourfold long incubation than BSE. Scrapie, as recently evoked in humanized mice (Cassard, 2014),
***is the third potentially zoonotic PD (with BSE and L-type BSE),
***thus questioning the origin of human sporadic cases.
We will present an updated panorama of our different transmission studies and discuss the implications of such extended incubation periods on risk assessment of animal PD for human health.
===============
***thus questioning the origin of human sporadic cases***
===============
***our findings suggest that possible transmission risk of H-type BSE to sheep and human. Bioassay will be required to determine whether the PMCA products are infectious to these animals.
==============
https://prion2015.files.wordpress.com/2015/05/prion2015abstracts.pdf
***Transmission data also revealed that several scrapie prions propagate in HuPrP-Tg mice with efficiency comparable to that of cattle BSE. While the efficiency of transmission at primary passage was low, subsequent passages resulted in a highly virulent prion disease in both Met129 and Val129 mice.
***Transmission of the different scrapie isolates in these mice leads to the emergence of prion strain phenotypes that showed similar characteristics to those displayed by MM1 or VV2 sCJD prion.
***These results demonstrate that scrapie prions have a zoonotic potential and raise new questions about the possible link between animal and human prions.
http://www.tandfonline.com/doi/abs/10.1080/19336896.2016.1163048?journalCode=kprn20
Prion diseases (PD) are the unique neurodegenerative proteinopathies reputed to be transmissible under field conditions since decades. The transmission of Bovine Spongiform Encephalopathy (BSE) to humans evidenced that an animal PD might be zoonotic under appropriate conditions. Contrarily, in the absence of obvious (epidemiological or experimental) elements supporting a transmission or genetic predispositions, PD, like the other proteinopathies, are reputed to occur spontaneously (atpical animal prion strains, sporadic CJD summing 80% of human prion cases).
Non-human primate models provided the first evidences supporting the transmissibiity of human prion strains and the zoonotic potential of BSE. Among them, cynomolgus macaques brought major information for BSE risk assessment for human health (Chen, 2014), according to their phylogenetic proximity to humans and extended lifetime. We used this model to assess the zoonotic potential of other animal PD from bovine, ovine and cervid origins even after very long silent incubation periods.
*** We recently observed the direct transmission of a natural classical scrapie isolate to macaque after a 10-year silent incubation period,
***with features similar to some reported for human cases of sporadic CJD, albeit requiring fourfold long incubation than BSE. Scrapie, as recently evoked in humanized mice (Cassard, 2014),
***is the third potentially zoonotic PD (with BSE and L-type BSE),
***thus questioning the origin of human sporadic cases.
We will present an updated panorama of our different transmission studies and discuss the implications of such extended incubation periods on risk assessment of animal PD for human health.
===============
***thus questioning the origin of human sporadic cases***
===============
***our findings suggest that possible transmission risk of H-type BSE to sheep and human. Bioassay will be required to determine whether the PMCA products are infectious to these animals.
==============
https://prion2015.files.wordpress.com/2015/05/prion2015abstracts.pdf
***Transmission data also revealed that several scrapie prions propagate in HuPrP-Tg mice with efficiency comparable to that of cattle BSE. While the efficiency of transmission at primary passage was low, subsequent passages resulted in a highly virulent prion disease in both Met129 and Val129 mice.
***Transmission of the different scrapie isolates in these mice leads to the emergence of prion strain phenotypes that showed similar characteristics to those displayed by MM1 or VV2 sCJD prion.
***These results demonstrate that scrapie prions have a zoonotic potential and raise new questions about the possible link between animal and human prions.
http://www.tandfonline.com/doi/abs/10.1080/19336896.2016.1163048?journalCode=kprn20
PRION 2016 TOKYO
Saturday, April 23, 2016
SCRAPIE WS-01: Prion diseases in animals and zoonotic potential 2016
Prion. 10:S15-S21. 2016 ISSN: 1933-6896 printl 1933-690X online
Taylor & Francis
Prion 2016 Animal Prion Disease Workshop Abstracts
WS-01: Prion diseases in animals and zoonotic potential
Transmission of the different scrapie isolates in these mice leads to the emergence of prion strain phenotypes that showed similar characteristics to those displayed by MM1 or VV2 sCJD prion.
These results demonstrate that scrapie prions have a zoonotic potential and raise new questions about the possible link between animal and human prions.
http://www.tandfonline.com/doi/abs/10.1080/19336896.2016.1163048?journalCode=kprn20
Title: Transmission of scrapie prions to primate after an extended silent incubation period)
*** In complement to the recent demonstration that humanized mice are susceptible to scrapie, we report here the first observation of direct transmission of a natural classical scrapie isolate to a macaque after a 10-year incubation period. Neuropathologic examination revealed all of the features of a prion disease: spongiform change, neuronal loss, and accumulation of PrPres throughout the CNS.
*** This observation strengthens the questioning of the harmlessness of scrapie to humans, at a time when protective measures for human and animal health are being dismantled and reduced as c-BSE is considered controlled and being eradicated.
*** Our results underscore the importance of precautionary and protective measures and the necessity for long-term experimental transmission studies to assess the zoonotic potential of other animal prion strains.
http://www.ars.usda.gov/research/publications/publications.htm?SEQ_NO_115=313160
1: J Infect Dis 1980 Aug;142(2):205-8
Oral transmission of kuru, Creutzfeldt-Jakob disease, and scrapie to nonhuman primates.
Gibbs CJ Jr, Amyx HL, Bacote A, Masters CL, Gajdusek DC.
Kuru and Creutzfeldt-Jakob disease of humans and scrapie disease of sheep and goats were transmitted to squirrel monkeys (Saimiri sciureus) that were exposed to the infectious agents only by their nonforced consumption of known infectious tissues. The asymptomatic incubation period in the one monkey exposed to the virus of kuru was 36 months; that in the two monkeys exposed to the virus of Creutzfeldt-Jakob disease was 23 and 27 months, respectively; and that in the two monkeys exposed to the virus of scrapie was 25 and 32 months, respectively. Careful physical examination of the buccal cavities of all of the monkeys failed to reveal signs or oral lesions. One additional monkey similarly exposed to kuru has remained asymptomatic during the 39 months that it has been under observation.
snip...
The successful transmission of kuru, Creutzfeldt-Jakob disease, and scrapie by natural feeding to squirrel monkeys that we have reported provides further grounds for concern that scrapie-infected meat may occasionally give rise in humans to Creutzfeldt-Jakob disease.
PMID: 6997404
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6997404&dopt=Abstract
Recently the question has again been brought up as to whether scrapie is transmissible to man. This has followed reports that the disease has been transmitted to primates. One particularly lurid speculation (Gajdusek 1977) conjectures that the agents of scrapie, kuru, Creutzfeldt-Jakob disease and transmissible encephalopathy of mink are varieties of a single "virus". The U.S. Department of Agriculture concluded that it could "no longer justify or permit scrapie-blood line and scrapie-exposed sheep and goats to be processed for human or animal food at slaughter or rendering plants" (ARC 84/77)" The problem is emphasised by the finding that some strains of scrapie produce lesions identical to the once which characterise the human dementias"
Whether true or not. the hypothesis that these agents might be transmissible to man raises two considerations. First, the safety of laboratory personnel requires prompt attention. Second, action such as the "scorched meat" policy of USDA makes the solution of the scrapie problem urgent if the sheep industry is not to suffer grievously.
snip...
76/10.12/4.6
Nature. 1972 Mar 10;236(5341):73-4.
Transmission of scrapie to the cynomolgus monkey (Macaca fascicularis).
Gibbs CJ Jr, Gajdusek DC.
Nature 236, 73 - 74 (10 March 1972); doi:10.1038/236073a0
Transmission of Scrapie to the Cynomolgus Monkey (Macaca fascicularis)
C. J. GIBBS jun. & D. C. GAJDUSEK
National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, Maryland
SCRAPIE has been transmitted to the cynomolgus, or crab-eating, monkey (Macaca fascicularis) with an incubation period of more than 5 yr from the time of intracerebral inoculation of scrapie-infected mouse brain. The animal developed a chronic central nervous system degeneration, with ataxia, tremor and myoclonus with associated severe scrapie-like pathology of intensive astroglial hypertrophy and proliferation, neuronal vacuolation and status spongiosus of grey matter. The strain of scrapie virus used was the eighth passage in Swiss mice (NIH) of a Compton strain of scrapie obtained as ninth intracerebral passage of the agent in goat brain, from Dr R. L. Chandler (ARC, Compton, Berkshire).
Wednesday, February 16, 2011
IN CONFIDENCE
SCRAPIE TRANSMISSION TO CHIMPANZEES
IN CONFIDENCE
reference...
RB3.20
TRANSMISSION TO CHIMPANZEES
1. Kuru and CJD have been successfully transmitted to chimpanzees but scrapie and TME have not.
2. We cannot say that scrapie will not transmit to chimpanzees. There are several scrapie strains and I am not aware that all have been tried (that would have to be from mouse passaged material). Nor has a wide enough range of field isolates subsequently strain typed in mice been inoculated by the appropriate routes (i/c, ilp and i/v) :
3. I believe the proposed experiment to determine transmissibility, if conducted, would only show the susceptibility or resistance of the chimpanzee to infection/disease by the routes used and the result could not be interpreted for the predictability of the susceptibility for man. Proposals for prolonged oral exposure of chimpanzees to milk from cattle were suggested a long while ago and rejected.
4. In view of Dr Gibbs' probable use of chimpazees Mr Wells' comments (enclosed) are pertinent. I have yet to receive a direct communication from Dr Schellekers but before any collaboration or provision of material we should identify the Gibbs' proposals and objectives.
5. A positive result from a chimpanzee challenged severely would likely create alarm in some circles even if the result could not be interpreted for man. I have a view that all these agents could be transmitted provided a large enough dose by appropriate routes was given and the animals kept long enough. Until the mechanisms of the species barrier are more clearly understood it might be best to retain that hypothesis.
6. A negative result would take a lifetime to determine but that would be a shorter period than might be available for human exposure and it would still not answer the question regarding mans' susceptibility. In the meantime no doubt the negativity would be used defensively. It would however be counterproductive if the experiment finally became positive. We may learn more about public reactions following next Monday' s meeting.
R. Bradley
23 September 1990
CVO (+Mr Wells' comments)
Dr T W A Little
Dr B J Shreeve
90/9.23/1.1.
http://web.archive.org/web/20090506041740/http://www.bseinquiry.gov.uk/files/yb/1990/09/23001001.pdf
IN CONFIDENCE CHIMPANZEES
CODE 18-77 Reference RB3.46
Some further information that may assist in decision making has been gained by discussion with Dr Rosalind Ridley.
She says that careful study of Gajdusek's work shows no increased susceptibility of chimpanzees over New World Monkeys such as Squirrel Monkeys. She does not think it would tell you anything about the susceptibility to man. Also Gajdusek did not, she believes, challenge chimpanzees with scrapie as severely as we did pigs and we know little of that source of scrapie. Comparisons would be difficult. She also would not expect the Home Office to sanction such experiments here unless there was a very clear and important objective that would be important for human health protection. She doubted such a case could be made. If this is the case she thought it would be unethical to do an experiment abroad because we could not do it in our own country.
Retrospectively she feels they should have put up more marmosets than they did. They all remain healthy. They would normally regard the transmission as negative if no disease resulted in five years.
We are not being asked for a decision but I think that before we made one we should gain as much knowledge as we can. If we decided to proceed we would have to bear any criticisms for many years if there was an adverse view by scientists ormedia. This should not be undertaken lightly. There is already some adverse comment here, I gather, on the pig experiment though that will subside.
The Gibbs' (as' distinct from Schellekers') study is somewhat different. We are merely supplying material for comparative studies in a laboratory with the greatest experience of human SEs in the world and it has been sanctioned by USDA (though we do not know for certain yet if chimpanzees specifically will be used). This would keep it at a lower profile than if we conducted such an experiment in the UK or Europe.
I consider we must have very powerful and defendable objectives to go beyond Gibbs' proposed experiments and should not initiate others just because an offer has been made.
Scientists have a responsibility to seek other methods of investigative research other than animal experimentation. At present no objective has convinced me we need to do research using Chimpanzees - a species in need of protection. Resisting such proposals would enable us to communicate that information to the scientist and the public should the need arise. A line would have been drawn.
CVO cc Dr T Dr B W A Little Dr B J Shreeve
R Bradley
26 September 1990
90/9.26/3.2
http://web.archive.org/web/20090506041605/http://www.bseinquiry.gov.uk/files/yb/1990/09/26003001.pdf
this is tse prion political theater here, i.e. what i call TSE PRION POKER...tss
3. Prof. A. Robertson gave a brief account of BSE. The US approach was to accord it a very low profile indeed. Dr. A Thiermann showed the picture in the ''Independent'' with cattle being incinerated and thought this was a fanatical incident to be avoided in the US at all costs.
snip...
PAGE 26
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.
The occurrence of CWD must be viewed against the contest of the locations in which it occurred. It was an incidental and unwelcome complication of the respective wildlife research programmes. Despite its subsequent recognition as a new disease of cervids, therefore justifying direct investigation, no specific research funding was forthcoming. The USDA veiwed it as a wildlife problem and consequently not their province! ...page 26.
snip...see;
IN CONFIDENCE
PERCEPTIONS OF UNCONVENTIONAL SLOW VIRUS DISEASE OF ANIMALS IN THE USA
GAH WELLS
REPORT OF A VISIT TO THE USA
APRIL-MAY 1989
MONDAY, DECEMBER 16, 2019
Chronic Wasting Disease CWD TSE Prion aka mad cow type disease in cervid Zoonosis Update
***> ''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) <***
What if?
FRIDAY, JULY 26, 2019
Chronic Wasting Disease in Cervids: Implications for Prion Transmission to Humans and Other Animal Species
THURSDAY, APRIL 08, 2021
Pennsylvania 2020 2021 had 162 CWD Violations with 196 Positive for the year
WEDNESDAY, APRIL 07, 2021
Minnesota 3-year-old white-tailed doe at a Beltrami County farm has been confirmed CWD positive
MONDAY, FEBRUARY 22, 2021
Minnesota Nine more deer added to tally of CWD positive whitetails at Houston County farm
TUESDAY, APRIL 06, 2021
Mississippi House Bill 382 high fence enclosures exempt from reporting cases of Chronic Wasting Disease is absurd
FRIDAY, MARCH 12, 2021
Michigan CWD identified in a Montcalm County farmed deer with 202 cases confirmed to date
THURSDAY, MARCH 18, 2021
Wisconsin Burnett County Deer Herd Depopulated Due to CWD
MONDAY, MARCH 08, 2021
OHIO SECOND POSITIVE CWD TISSUE SAMPLE IDENTIFIED IN WILD
SUNDAY, NOVEMBER 08, 2020
OHIO CHRONIC WASTING DISEASE TSE PRION UPDATE TO DATE 24 CWD POSITIVES IN CAPTIVE CERVID ZERO IN WILD
THURSDAY, JULY 30, 2020
Ohio Deer Summary 2019 - 2020 CWD TSE Prion 24 Confirmed To Date All Captive Cervid
SATURDAY, MAY 16, 2020
Ohio Chronic Wasting Disease Detected on Wayne County Farm
Control of Chronic Wasting Disease OMB Control Number: 0579-0189 APHIS-2021-0004 Singeltary Submission
Greetings APHIS et al, i would kindly like to comment on Control of Chronic Wasting Disease OMB Control Number: 0579-0189 APHIS-2021-0004.
Greetings APHIS et al, i would kindly like to comment on Control of Chronic Wasting Disease OMB Control Number: 0579-0189 APHIS-2021-0004.
***> 1st and foremost your biggest problem is 'VOLUNTARY'! AS with the BSE 589.2001 FEED REGULATIONS, especially since it is still voluntary with cervid, knowing full well that cwd and scrapie will transmit to pigs by oral route. VOLUNTARY DOES NOT WORK! all animal products should be banned and be made mandatory, and the herd certification program should be mandatory, or you don't move cervid. IF THE CWD HERD CERTIFICATION IS NOT MANDATORY, it will be another colossal tse prion failure from the start.
***> 2nd USA should declare a Declaration of Extraordinary Emergency due to CWD, and all exports of cervid and cervid products must be stopped internationally, and there should be a ban of interstate movement of cervid, until a live cwd test is available.
***> 3rd Captive Farmed cervid ESCAPEES should be made mandatory to report immediately, and strict regulations for those suspect cwd deer that just happen to disappear. IF a cervid escapes and is not found, that farm should be indefinitely shut down, all movement, until aid MIA cervid is found, and if not ever found, that farm shut down permanently.
***> 4th Captive Farmed Cervid, INDEMNITY, NO MORE Federal indemnity program, or what i call, ENTITLEMENT PROGRAM for game farm industry. NO MORE BAIL OUTS FROM TAX PAYERS. if the captive industry can't buy insurance to protect not only themselves, but also their customers, and especially the STATE, from Chronic Wasting Disease CWD TSE Prion or what some call mad deer disease and harm therefrom, IF they can't afford to buy that insurance that will cover all of it, then they DO NOT GET A PERMIT to have a game farm for anything. This CWD TSE Prion can/could/has caused property values to fall from some reports in some places. roll the dice, how much is a state willing to lose?
***> 5th QUARANTINE OF ALL FARMED CAPTIVE, BREEDERS, URINE, ANTLER, VELVET, SPERM, OR ANY FACILITY, AND THEIR PRODUCTS, that has been confirmed to have Chronic Wasting Disease CWD TSE Prion, the QUARANTINE should be for 21 years due to science showing what scrapie can do. 5 years is NOT near long enough. see; Infectious agent of sheep scrapie may persist in the environment for at least 16 to 21 years.
***> 6th America BSE 589.2001 FEED REGULATIONS CWD TSE Prion
***> 7TH TRUCKING TRANSPORTING CERVID CHRONIC WASTING DISEASE TSE PRION VIOLATING THE LACEY ACT
***> 8TH ALL CAPTIVE FARMING CERVID OPERATIONS MUST BE INSURED TO PAY FOR ANY CLEAN UP OF CWD AND QUARANTINE THERE FROM FOR THE STATE, NO MORE ENTITLEMENT PROGRAM FOR CERVID GAME FARMING PAY TO PLAY FOR CWD TSE PRION OFF THE TAX PAYERS BACK.
***> 9TH ANY STATE WITH DOCUMENTED CWD, INTERSTATE, NATIONAL, AND INTERNATIONAL MOVEMENT OF ALL CERVID, AND ALL CERVID PRODUCTS MUST BE HALTED!
***> 10TH BAN THE SALE OF STRAW BRED BUCKS AND ALL CERVID SEMEN AND URINE PRODUCTS
***> 11th ALL CAPTIVE FARMED CERVID AND THEIR PRODUCTS MUST BE CWD TSE PRION TESTED ANNUALLY AND BEFORE SALE FOR CWD TSE PRION
Control of Chronic Wasting Disease OMB Control Number: 0579-0189 APHIS-2021-0004 Singeltary Submission
Comment ID
APHIS-2021-0004-0002
Terry S. Singeltary Sr.
posted by Terry S. Singeltary Sr. at
3:54 PM
0 Comments
