CHRONIC WASTING DISEASE IN UK DEER SEAC 85/2
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Subject: CHRONIC WASTING DISEASE IN UK DEER SEAC 85/2
Date: Sat, 27 Nov 2004 16:07:38 -0600
From: "Terry S. Singeltary Sr."
Reply-To: Bovine Spongiform Encephalopathy To: BSE-L@LISTSERV.KALIV.UNI-KARLSRUHE.DE
##################### Bovine Spongiform Encephalopathy #####################
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SEAC 85/2
CHRONIC WASTING DISEASE IN UK DEER
ISSUE
1. The FSA have asked SEAC to consider the current knowledge on, and comment on the possible public and animal health implications of, CWD in UK deer.
BACKGROUND
2. Over the past few decades, chronic wasting disease (CWD) has emerged as an endemic transmissible spongiform encephalopathy (TSE) in a number of captive and free-ranging cervid species (mule and white-tailed deer and Rocky Mountain elk) in some areas of North America. To date, CWD has not been detected elsewhere in the world. CWD is naturally transmissible from infected to susceptible cervids. The primary route(s) of infection are unclear but it is possible that it may be transmitted via contaminated environments. The origins of the disease are unknown. CWD is the only known TSE to occur naturally in cervids.
3. CWD is experimentally transmissible to non-cervid species by intracerebral inoculation. Very few studies have investigated experimental transmission to non-cervid species by oral routes that may mimic the possible natural route(s) of infection. In these studies, oral transmission of CWD has only been successful to North American cervid species. Thus, it is unclear whether CWD could be naturally transmitted to other cervid and non-cervid species.
4. There is very limited epidemiological data on the possible transmission of CWD to humans as a result of consumption of infected venison. No definitive or suspected cases of transmission of CWD to humans have been reported. Thus, it is not known whether CWD can be transmitted to humans from consumption of venison.
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5. It is likely, prior to the reinforced mammalian meat and bone meal (MMBM) ban in 1996, that both captive and free-ranging deer species in the UK, and possibly elsewhere in Europe, were exposed to contaminated feed. Studies investigating experimental transmission of BSE to cervids have not been completed. Although no TSEs have been detected in deer populations in the UK (or elsewhere in Europe), surveillance data are limited. Thus, it is possible that BSE may have been transmitted to, and could be present in, UK deer. If present, deer infected with BSE could present a risk to consumers of venison.
SEAC CONSIDERATION
6. SEAC has not considered CWD previously. The committee is asked to consider the possible public and animal health implications of CWD in UK deer with a view to producing a SEAC position statement. The literature on CWD is extensive. It is therefore, envisaged that this consideration could be conducted over two consecutive meetings. The first meeting (SEAC 85) would consider the current knowledge on TSEs in deer. A list of possible areas for discussion is given at the end of the paper with a view to formulating a draft position statement and identifying key issues and questions for further discussion at the next meeting (SEAC 86). If SEAC require, it may be possible to invite an expert on CWD to SEAC 86 to provide additional expertise for consideration of the key issues identified.
7. This paper provides the following information:
" Two recent scientific reviews on CWD from the Wildlife Information Network (October 2004) and the EU Scientific Steering Committee (March 2003).
" An overview of the UK deer industry (2002).
" A summary of current TSE surveillance in deer in the UK and elsewhere in Europe as well as an EFSA opinion on TSE surveillance in deer.
" A summary of current FSA research on the susceptibility of UK red deer to BSE infection.
" Possible exposure of UK deer to TSEs as well as sources and consumption of venison in the UK.
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REVIEWS OF CWD
Wildlife Information Network
8. A review of available scientific literature (up to October 2004) on CWD has been prepared by the Wildlife Information Network (Annex 1). It covers current knowledge in the following areas:
" Distribution and host range
" Diagnosis and detection
" Epidemiology
" Susceptibility and routes of transmission
" Public and animal health implications
Scientific Steering Committee
9. The TSE/BSE ad hoc group of the EU Scientific Steering Committee (SSC) conducted a review of the scientific literature on CWD in March 2003 (Annex 2). The SSC concluded that:
A theoretical risk for prion transmission to humans consuming products of CWD affected-cervids of all ages in countries where CWD exists cannot be excluded. Similarly, a transmission risk of prions to domestic animals cannot be excluded. There is therefore, a scientific basis on which to exclude tissues from animals that carry a CWD risk from the human and animal feed chains.
However, the early and widespread involvement of tissues in CWD infected animals does not allow a SRM list, neither to define any lower age cut-off as has been defined for cattle in relation to BSE. Neither is there sufficient knowledge to define exclusions or amendment of any SRM rule of the basis of relative genetic resistance to infection as has been proposed for sheep and goats in the event that evidence indicates the probable natural occurrence of BSE in these species.
Although available information indicates imports of live Cervidae from North America to EU and trade in meat products from cervid species as being negligible, it is important to reach certainty that no transfer of risk takes place through trade of live cervids and its derived products.
At present, there is no scientific data that CWD is occurring in Cervidae elsewhere than in those countries from which it has previously been reported. However, systematic TSE surveillance
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of cervid populations has either been absent or has only just started in European countries. Until the results of such surveillance become available no conclusion can be drawn with regard to the occurrence of CWD or similar TSE in the cervid population of Europe.
REPORT ON THE UK DEER INDUSTRY
10. Information on the deer industry and venison trade in the UK is limited. A 2002 report by Professor Ranald Munro (Royal (Dick) School of Veterinary Studies, Edinburgh) provides an overview of the type (wild, farmed, park or zoo), size and geographical distribution of the five main deer species in the UK (Annex 3). Information on trading and slaughter practices, routes of supply of venison into the food chain and disposal of fallen stock and byproducts is also provided. The report was commissioned by Defra and FSA to inform surveys of TSEs in UK.
11. In the report, Professor Munro makes a number of observations about the possibility of TSEs in UK deer (pages 43 and 48-50):
" Although surveillance is limited, as yet, CWD has not been found in deer populations in the UK.
" Prior to the reinforced MMBM ban in 1996, deer were exposed to feed potentially contaminated with MMBM.
" Red deer, a deer species prevalent in the UK, are closely related to Rocky Mountain elk (a North American species known to be susceptible to CWD). Thus, of the five principal UK deer species (red, roe, fallow, sika and muntjac), red deer may be the UK species with the greatest potential to develop TSEs.
" Early in the BSE epidemic, cases of BSE occurred in zoological collections of a number of species (antelope, Ankole cattle, bison, eland, oryx, gemsbok, kudu and nyala) presumably from the use of feed concentrates contaminated with MMBM. Although deer in zoos were fed similar concentrates, there are no reports of BSE cases in these animals.
SURVEILLANCE OF TSEs IN EUROPEAN DEER
12. Limited surveys have been carried out for TSEs in European deer populations but, to date, these programmes have not reported
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TSE cases. A summary of TSE surveys of deer in the UK and other EU Member States is given at Annex 4.
13. The European Food Safety Authority (EFSA) recently published an opinion on proposals for an EU surveillance programme for TSEs in deer (2004) (Annex 5). The opinion is under consideration by the EU.
FSA RESEARCH ON TSEs IN DEER
14. A FSA funded study is underway to investigate if UK red deer (a species closely related to Rocky Mountain elk) are susceptible to BSE infection by oral or intracerebral challenge (Annex 6). The study is in its early stages and is due to complete in 2007. To date, there are no clinical or pathological signs of BSE in orally or intracerebrally challenged animals at 12 or 6 months postadministration, respectively. Please note that Annex 6 has not been circulated outside the committee as it contains new scientific data that has not yet been published in a scientific journal.
ANIMAL EXPOSURE AND VENISON CONSUMPTION
Potential exposure of UK deer to TSEs
CWD
15. No live cervids from North America have been imported into the EU (see Annex 2, page 38). In addition, HM Customs and Excise have no record of imports of live cervids from North America into the UK. Thus, opportunities for natural transmission of CWD from infected animals imported from North America into the UK or Europe have not been available.
BSE
16. There are no quantitative data that would allow an estimation of past exposure of wild, farmed or park (and zoo) deer to animal feed containing MMBM. However, it appears likely that each of these deer populations consumed MMBM to some extent (see Annex 3 page 10).
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Sources and consumption of deer and elk products in the UK 17. In the UK, much of the venison from wild deer is exported (see Annex 3, pages 29-33). However, most venison from UK farmed deer is sold in the UK (see Annex 3, pages 38-39).
18. Specific figures for imports of edible deer and elk products from North America into the EU are not available. However, figures for game meat (excluding rabbits, hares and swine) suggest that a very limited quantity of deer and/or elk meat may have been imported from North America into the EU, including the UK, over the period 1988-2001 (see Annex 2, pages 51-52). More recent information (2001-2004) from HM Customs and Excise supports this conclusion.
19. There are few data on consumption of UK produced or imported venison. National Diet and Nutrition Surveys1,2,3 provide profiles of eating habits in the UK. An analysis of the surveys indicates that venison is rarely consumed in comparison with beef and lamb (of the combined total of 5608 consumers in the surveys, 2064 (37%) had consumed lamb, 4819 (86%) had consumed beef and 12 (0.2%) had consumed venison). Data on venison consumption from the surveys suggest a trend towards increased venison consumption (0.14% versus 0.41% of consumers ate venison in the years 1986/7 and 2000/1, respectively). However, the data are too limited to allow a quantitative assessment of venison consumption.
ADVICE SOUGHT FROM THE COMMITTEE
20. The committee is asked to consider the possible public and animal health implications of TSEs in UK deer with a view to producing a SEAC position statement. The FSA have asked that SEAC address the following question in the position statement:
" What is the level of risk posed to consumers from eating meat from a CWD infected animal?
21. To help its consideration the committee may wish to consider the following areas:
1J Gregory, K Fisher, H Tyler & M Wiseman. Dietary and Nutritional Survey of British Adults, HMSO, 1990.
2S Finch, W Doyle, S Lowe, C Bates, A Prentice, G Smithers & P Clarke. National Diet and Nutritional Survey;
People 65 Years and Over. Volume 1: Report of the Diet and Nutrition Survey, TSO 1998.
3L Henderson, J Gregory & G Swan. National Diet and Nutritional Survey; Adults Aged 19 to 65 years. Volume 1:
Types and Quantities of Foods Consumed, TSO 2002.
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" possible origins of CWD.
" possible routes of intra- and inter-species transmission of CWD.
" potential susceptibility of UK cervid and non-cervid (livestock) species to CWD.
" likelihood of the presence of TSEs in UK deer.
" possible human and animal health risks of TSEs in UK deer.
Are members aware of any other data that can add to the information in this paper?
Would the committee wish to invite an expert on CWD to the next meeting and, if so, could members suggest a particular expert?
http://www.seac.gov.uk/papers/tsesdeer-%20final.pdf
CWD Review / Dr Debra Bourne / October 2004 / For SEAC / Page 1 of 66
CHRONIC WASTING DISEASE REVIEW
Written by Dr Debra Bourne, Wildlife Information Network, October 2004, for SEAC
[Wildlife Information Network (WIN) is a UK Registered Charity (No. 1048059) WINs aim is to "disseminate information on the health and management of free-ranging and captive animals and their environments, together with emerging infectious diseases, to professionals and decision-makers worldwide." The main way in which WIN achieves this is through development of the WildPro® Electronic Encyclopaedia, which is made available through a website (www.wildlifeinformation.org) and as CD-ROM volumes.]
CWD Review / Dr Debra Bourne / October 2004 / For SEAC / Page 2 of 66 RESOURCES USED IN WRITING THIS REVIEW
This review was based on a peer-reviewed Wildlife Information Network CD-ROM (Wildpro v5.0 Chronic Wasting Disease in Deer and Elk (Bourne, D.C., Dein, F.J. & Boardman, S.I. (eds.). Wildlife Information Network, Twycross, UK. ISBN 0-9547185-4- 2. This volume of Wildpro is accessible at www.wildlifeinformation.org and was based on references found by the following methods:
" Searches on PubMed using various keywords including CWD , Chronic Wasting Disease and transmissible spongiform encephalopathy , together with other keywords (transmissible mink encephalopathy/TME, feline spongiform encephalopathy/FSE etc.) for comparative data. Searches were also carried out using names of key authors, e.g. ORourke and Williams, ES .
" Searches on Agricola, Biological Abstracts, CAB Abstracts, Wildlife Worldwide and Zoological Record. Keywords used included chronic wasting disease, CWD, transmissible spongiform encephalopathies, bovine spongiform encephalopathy, scrapie, transmissible mink encephalopathy, fatal familial insomnia, kuru, Gerstmann- Straussler-Scheinker, feline spongiform encephalopathy and nvCJD. " Abstracts of papers found from database searches were read and relevant papers (all papers on CWD plus key and review papers on other TSEs/general prion science) were then examined in more detail.
" For key journals such as Emerging Infectious Diseases and Journal of General Virology, the contents list of every volume was checked, or keyword searches were performed on the website of the individual journal. " Reference lists of papers on CWD were traced backwards, particularly those from both recent and early review articles on the topic. Similar tracing back was performed for papers on other TSEs and general papers on TSEs/prion science, where this was felt appropriate.
" Key proceedings were checked, e.g. proceedings of conferences on CWD/TSEs and certain other conferences such as the Proceedings of the Wildlife Disease Association and the US Animal Health Association.
" Reference lists on CWD/TSEs compiled by other organisations were checked, particularly that of the National Wildlife Health Center, USGS
" ProMED-Mail was utilised as a means of detecting emerging information, for example initial reports of findings of CWD in new geographical areas.
" For data on geographical range and incidence, relevant federal and state/provincial websites were searched, e.g. CFIA, APHIS, Colorado Fish & Game, Wisconsin Department of Natural Resources. Such sites also provided additional material such as the Wisconsin DNRs Environmental Impact Statement and An Analysis of Risks Associated with the Disposal of Deer from Wisconsin in Municipal Solid Waste Landfill.
" Published data from journals, books, proceedings and Websites was supplemented by personal communications from people working on CWD in Wisconsin and elsewhere in the USA
In addition, for this report, data specifically concerning CWD was updated by searches on PubMed, tracking back from recent papers, checking key websites and key journals and using some more general web searches (on Google) using carefully chosen keyword combinations.
Very recent findings were confirmed or expanded, where required, by contacting key researchers. CWD Review / Dr Debra Bourne / October 2004 / For SEAC / Page 3 of 66
CONTENTS
1) INTRODUCTION................................................................................................................
5 2) EMERGENCE, AETIOLOGY AND POSSIBLE ORIGINS ..........................................
5 Emergence/History.................................................................................................................
5 Aetiology...............................................................................................................................
6 Strains of CWD? ................................................................................................................
6 Possible Origins of CWD.......................................................................................................
7 Scrapie...............................................................................................................................
7 Development from a spontaneous or genetic SE in mule deer ..........................................
8 Unknown source.................................................................................................................
9 Alternative suggestions considered and rejected ...............................................................
9 Familial or genetic association.......................................................................................
9 Animal protein fed to the deer........................................................................................
9 3) KNOWN GEOGRAPHICAL DISTRIBUTION AND TIMELINES OF SPREAD......
9 In captive cervids ...................................................................................................................
9 In research facilities .........................................................................................................
10 In farmed cervids..............................................................................................................
10 Canada.........................................................................................................................
10 USA.............................................................................................................................
11 Outside North America ................................................................................................
12 In free-ranging cervids .........................................................................................................
12 USA.................................................................................................................................
12 Canada.............................................................................................................................
16 Outside North America ....................................................................................................
16 4) HOST RANGE...................................................................................................................
16 Known natural hosts.............................................................................................................
16 Experimental transmission by intracerebral inoculation......................................................
16 Experimental transmission by oral inoculation....................................................................
18 Experimental transmission by contact..................................................................................
19 Natural transmission by contact/environmental contamination ...........................................
19 5) CWD IN THE KNOWN NATURAL HOSTS.................................................................
19 Clinical signs in cervids .......................................................................................................
19 Clinical signs in Cervus elaphus nelsoni..........................................................................
20 Clinical signs in Odocoileus hemionus ............................................................................
20 Clinical signs in Odocoileus virginianus .........................................................................
21 Incubation period in cervids.................................................................................................
21 Morbidity/mortality in cervids .............................................................................................
22 Pathological findings............................................................................................................
22 Gross pathology................................................................................................................
22 Histopathology .................................................................................................................
23 Electron microscopy.........................................................................................................
23 PrP deposition ..................................................................................................................
24 Pathogenesis .........................................................................................................................
25 Early lymphoid tropism....................................................................................................
25 Changes in distribution of PrP and lesions with time during infection............................
26 Variations between species ..............................................................................................
26 Individual variation ..........................................................................................................
27 6) DIAGNOSIS .......................................................................................................................
27 Histopathology .....................................................................................................................
27 Immunohistochemistry.........................................................................................................
28 Electron microscopy.............................................................................................................
29 Other tests............................................................................................................................
29 CWD Review / Dr Debra Bourne / October 2004 / For SEAC /
Page 4 of 66
ELISA..............................................................................................................................
30 Immunoblotting................................................................................................................
30 Conformation-dependent immunoassay (CDI) ................................................................
31 Limitations of rapid tests......................................................................................................
31 Choice of tissues for testing .................................................................................................
32 7) EPIDEMIOLOGY AND TRANSMISSION....................................................................
32 Potential sources and transmission routes............................................................................
33 Contact .............................................................................................................................
34 From enclosures previously used by infected animals.....................................................
34 From carcasses .................................................................................................................
34 Problems of eradication/environmental contamination........................................................
35 Epidemiology and spread in captive and farmed cervids.....................................................
35 Epidemiology and spread in free-ranging cervids................................................................
36 8) SUSCEPTIBILITY WITHIN THE KNOWN NATURAL HOSTS..............................
38 Genetics in Cervus elaphus nelsoni .....................................................................................
38 Genetics in Odocoileus hemionus ........................................................................................
38 Genetics in Odocoileus virginianus .....................................................................................
39 Age specific susceptibility?..................................................................................................
40 Effect of sex on susceptibility? ............................................................................................
41 9) ANIMAL HEALTH CONCERNS ...................................................................................
42 Potential risk to other Cervidae............................................................................................
42 Surveillance studies..........................................................................................................
42 Reindeer (caribou) Rangifer tarandus.......................................................................
43 Common European deer species red deer Cervus elaphus elaphus, roe deer Capreolus capreolus and fallow deer Dama dama......................................................
43 Potential risk to domestic cattle & sheep .............................................................................
44 Potential risk to other species...............................................................................................
44 10) HUMAN HEALTH CONCERNS ..................................................................................
44 Epidemiological investigations ............................................................................................
45 Laboratory studies ................................................................................................................
47 Potential risk from consuming cervid products....................................................................
48 Velvet antler .....................................................................................................................
48 Consumption of venison and other parts of the animal....................................................
48 Potential risk from handling and processing cervids ...........................................................
48 Potential risk from disposal of carcasses and subsequent contamination of ground/water/air .............................................................................................................................................
48 TABLES.................................................................................................................................
49 Table 1: Summary of results of CWD transmission experiments........................................
49 Table 2: Summary of PRNP gene differences between species and polymorphisms within species for the known natural hosts of CWD.......................................................................
52 Table 3: Comparison of PRNP sequence variations from some North American and European cervid species .......................................................................................................
53 REFERENCES......................................................................................................................
54
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CWD Review / Dr Debra Bourne / October 2004 / For SEAC /
Page 44 of 66
Potential risk to domestic cattle & sheep 211.
To date, no transmission of CWD has been reported in domestic species living in CWD endemic areas or in research facilities with CWD. Monitoring is ongoing (Gould et al., 2003; Williams & Miller 2002; Belay et al., 2004). It has been possible to infect domestic cattle, goats and sheep by intracerebral inoculation, although not in all inoculated individuals (Hamir et al., 2003a; Hamir et al., 2004a); see paragraphs 66-67. Data from intracerebral inoculation experiments show that diagnostic methods currently in use for BSE surveillance would detect the CWD agent in cattle and sheep if it were present (Hamir et al., 2003a). 212. Data from in vitro experiments suggests that there may be a considerable species barrier limiting transmission of CWD from cervids to domestic cattle and, to a lesser extent, to domestic sheep. In a cell-free conversion system, PrPCWD from elk, mule deer or whitetailed deer showed 5-to-12-fold lower conversion efficiency of bovine PrP-sen than for intercervid conversion reactions; conversion efficiency of ovine PrP-sen (ovine PrP-AQ) was also less than half as efficient as for homologous cervid reactions (Raymond et al., 2000). 213. There is a theoretical risk than CWD could be transmitted to cattle via incorporation of infected tissue from Cervidae into meat and bone meal. The risk for this occurring in the USA was considered [in 1992] to be small because CWD is believed to be rare and localized, and the proportion of harvested Cervidae whose offal is rendered is probably small [in the USA] (Saunders, 1994). The feeding of ruminant-derived protein to ruminants has been banned in Canada and the USA since 1997 (Kahn et al., 2004). The US Food and Drug Administration (FDA) has, since November 2002, banned the use of material from Chronic Wasting Disease (CWD)-positive animals, or animals at high risk for CWD, to be used as an ingredient in feed for any animal species. Animals considered to be at high risk for CWD were stated to include animals from CWD-positive captive herds, free-ranging animals from the CWDendemic area in Colorado and Wyoming, deer from the CWD eradication zone in Wisconsin and also deer from any areas designated around any new foci of CWD infection that might be identified through surveillance or hunter harvest testing (FDA, 2002). Such policies should minimise the potential oral exposure of domestic ruminants to CWD-agent in feed. Potential risk to other species 214. Since BSE appears to have been transmitted orally to various Felidae (Kirkwood et al., 1995; Bourne, 2004b), the possibility of CWD being transmitted to carnivores must be considered. 215. Experimentally, CWD has been successfully transmitted by intracerebral inoculation to domestic ferrets (Mustela putorius fero) and to American mink (Mustela vison), but not to common raccoons (Procyon lotor) (Williams, Young & Marsh 1982; Williams & Young, 1992; Williams et al., 1992; Hamir et al., 2003c; Sigurdson et al., 2003). Since raccoons are highly adaptable carnivores which may include carrion in their diet (Hamir et al., 2003c), the lack of success in transmission of CWD to raccoons even by intracerebral inoculation is encouraging. 216. There is no published data on transmission or attempted transmission of CWD to felids or canids. 10) HUMAN HEALTH CONCERNS 217. To date there are no known cases of human prion disease attributable to CWD transmitted to humans (Belay et al., 2004). While limited epidemiological investigations to date have not shown any links between CWD and humans with spongiform encephalopathies CWD Review / Dr Debra Bourne / October 2004 / For SEAC / Page 45 of 66 this data must be considered along with a caveat: because CWD is a relatively new TSE, it is unlikely that enough people have consumed enough CWD-affected cervids to result in a clinically or pathologically recognizable disease attributable to CWD, especially considering the very long incubation periods characteristic of TSE diseases. (Race et al., 2002) Epidemiological investigations 218. Epidemiological investigations have failed to show any links between cases of prion disease in unusually young people or in hunters in the USA and CWD (CDC, 2003). Two major epidemiological investigations have been carried out, one on cases of CJD in unusually young individuals in the USA, the second on a group of men from Wisconsin who developed neurological diseases. 219. The first study (Belay et al., 2001) focused on three individuals, two 28 years of age and the third 30 years old, diagnosed with CJD in the USA between 1st January 1997 and 31st May 2000, and without any established risk factors for CJD (family history, receipt of human growth hormone, receipt of grafts of dura mater or cornea, or previous neurological surgery) and concluded that there was no strong evidence for a causal link with CWD. None of the individuals had travelled to Europe (therefore a link with BSE was unlikely). Two of the individuals were hunters who regularly consumed game meat while the third (case 1) had, as a young child, regularly consumed venison from animals hunted by family members and on two occasions from a family friend. Two of the individuals (cases 1 and 2) had undergone tonsillar surgery as children; the third had never received any surgical treatment. One individual (case 1) had eaten venison mainly hunted in Maine, occasionally hunted in New Jersey, and, on two occasions at about six years old, elk meat which had probably been harvested in Wyoming. The second person (case 2) had hunted cervids mainly in Utah, but had harvested an elk in southwestern Wyoming on one occasion (less than three years before onset of clinical signs) and had hunted in British Columbia on one occasion nine years before onset of illness. The third person (case 3) had hunted close to home and never in Colorado or Wyoming although the plant where he took his carcasses for processing did also process some elk from Colorado each year. The clinical signs, duration of illness and histopathological findings for the three individuals showed no obvious similarities to one another. One individual was methionine/methionine homozygous at codon 129 of the PRNP (case 1), one was homozygous for valine at this gene (case 2) and the third (case 3) was heterozygous methionine/valine. Immunohistochemistry revealed strong staining with a synaptic pattern in the first individual and weak staining with a synaptic pattern in the second case; in case 3, based on a brain biopsy sample obtained at an early point in the illness, staining was questionable and possibly showed a synaptic pattern. Cases 2 and 3 showed a Type 1 immunoblot pattern, this test had not been carried out for case 1. It was noted that none of these three individuals had a definite history of consumption of venison from the geographical areas in which CWD was known to be endemic in Colorado and Wyoming, and no CWD had been identified in 299 deer and sampled from the area in which most of the venison consumed by patient 1 had originated, nor in 404 deer and 196 elk sampled from the area in which most of the venison consumed by patient 2 had originated, nor in 138 deer samples from the area in which most of the venison consumed by patient 1 had originated. Additionally, there was no homogeneity in phenotypic expression of the disease and all three possible options for coding at codon 129 of the PRNP gene were represented. Since a survey had indicated that approximately 40% of blood donors in the USA consumed venison from wild cervids, it was considered most likely that coincidence explained why three of the four young (30 years old or younger) individuals with sporadic CJD reported in the USA after March 1996 had consumed such meat (Belay et al., 2001). CWD Review / Dr Debra Bourne / October 2004 / For SEAC / Page 46 of 66 220. The second major epidemiological investigation centred around three men from Wisconsin and Minnesota who had died from degenerative neurological illnesses and who had participated in wild game feasts in northern Wisconsin. Full investigation including examination of fixed brain tissue confirmed CJD in only one of the three individuals. Wild game eaten during the feasts was harvested mainly in Wisconsin but also in areas of Colorado, Wyoming and Montana; CWD was not known to be endemic in the areas where the game was hunted at the time that the game was harvested. Further investigations of other possible attendees of the feasts revealed 34 participants, all male, of whom a total of seven were deceased, including the three individuals in the initial investigation. Causes of death in the other four deceased individuals were not attributed to nor associated with any degenerative neurological disorder and no signs or symptoms associated with a degenerative neurological disorder were noted for any of the remaining living participants of the feasts. It was noted that only one case of CJD had occurred among known participants at the feasts, that this case was consistent with the commonest form of sporadic CJD, that this individual had only participated in one feast and that it was unlikely that he had consumed CWDinfected venison at the feasts because venison and other game from outside Wisconsin that was served at these feasts did not originate from known CWD-endemic areas. Limitations of the investigations were noted to include reliance on recall of events from up to 25 years previously and the fact that not all participants in the feasts could be contacted and interviewed. However, those who were interviewed agreed in their recall of events (CDC, 2003). 221. It is important to recognise that the limited epidemiological investigations that have been carried out are not able to rule out the possibility that CWD might play a role in causing illness in humans (CDC, 2003). 222. Three further cases of prion disease in young humans in the USA have been investigated for possible links to CWD (Belay et al., 2004). The first case was a 25-year-old man who died in 2001 after about 22 months of illness. Gerstmann- Sträussler-Scheinker syndrome (GSS) was diagnosed by analysis of the prion gene, with a P102L mutation together with valine at codon 129 in the mutant allele. It was noted that the disease had occurred at an unusually young age, even for GSS, and the possibility that exposure to CWDinfected venison contributed to early onset of the disease could not be ruled out; the patients grandfather had regularly hunted in southeastern Wyoming, around the known CWD-endemic area, and had given venison to the patients family. Two other cases of prion disease occurred in individuals of 26 and 28 years of age, from adjacent counties, and with onset of illness only months apart, therefore an environmental source of infection was investigated. However, these two individuals were finally diagnosed with different prion diseases: sporadic CJD in one case and GSS in the other, indicating that a common cause was unlikely. In the first case CJD was confirmed from autopsy samples (by histopathology, immunohistochemistry and immunoblotting); the individual had no history of hunting nor of regular consumption of venison, and although he may have eaten venison originating from the Upper Peninsula of Michigan while at college CWD has never been detected in deer from Michigan. Phenotypically this individual fit the MM2 sporadic CJD phenotype described by Parchi et al. (1999). In the other case post mortem immunohistochemistry revealed prion deposition which was consistent with GSS and a GSS P102L mutation was detected in a blood sample from one parent (appropriate samples were not available from the affected patient); this individual may possibly have eaten venison from Michigan on one occasion at about two years of age (Belay et al., 2004). 223. A further three cases of CJD in individuals of 54 to 66 years old who were deer and elk hunters (two individuals) or ate wild-harvested venison (one individual) have been CWD Review / Dr Debra Bourne / October 2004 / For SEAC / Page 47 of 66 investigated. There was no evidence that any of these individuals had hunted in known CWDendemic areas; information available indicated hunting or eating venison from Washington State and Pennsylvania. Two individuals were V/V at codon 129 the third was M/M; they were considered to fit known subtypes of sporadic CJD (MM1, VV1 and VV2 subtypes as described by Parchi et al. (1999)). Further investigations were also made on the only two nonfamilial cases of CJD in individuals with a history of eating venison from the known CWD-endemic areas. One was reported to have eaten venison from two deer harvested in an area with endemic CWD, but both deer had been tested and not found to be CWD-positive; the patients illness was consistent with the CJD subtype MM1. The other individual grew up in a CWD-endemic area and ate locally-harvested venison; her disease fit the MM1 CJD phenotype and no atypical neurological features were noted (Belay et al., 2004). 224. Additional epidemiological notes are that the incidence and age distribution of CJD in Colorado and Wyoming, where CWD is thought to have been endemic for decades, are similar to those found in other areas of the USA. In Wyoming, seven cases of CJD have been reported between 1979 and 2000 with an average annual age-adjusted CJD death rate of 0.8 per million and no cases reported in humans less than 55 years old. In Colorado in the same period 67 cases of CJD have been reported, with an average annual age-adjusted CJD death rate of 1.2 per million (Belay et al., 2004). 225. In summary, there is no evidence of an increase in incidence of CJD in Colorado and Wyoming, nor have epidemiological investigations carried out so far found any evidence of a link between CWD and cases of CJD in persons in the USA (Belay et al., 2001; CDC, 2003; Belay et al., 2004). Laboratory studies 226. There is evidence from an in vitro cell-free system that there may be a considerable species barrier reducing the probability that CWD will affect humans. It was shown that PrPres associated with chronic wasting disease (PrPCWD) from elk, mule deer or white-tailed deer was able to readily induce substantial conversion of recombinant cervid PrPsen molecules form any of these three species to the protease-resistant state. In the same system, CWD-associated PrPres was shown to convert human PrPsen but at a much lower efficiency: more than 14-fold lower efficiency than inter-cervid conversion reactions and more than fivefold lower than conversion of human PrPsen by PrPres from the brains of humans with CJD (Raymond et al., 2000). While encouraging, interpretation of this study is complicated by the fact that conversion of human PrPC by PrPBSE and PrPSc from sheep were of similar efficacy, both being more than 10-fold less efficient compared with corresponding homologous conversions) and one of these appears to be orally transmissible to humans (BSE) while the other (scrapie) appears not to be (Raymond et al., 2000). In previous experiments PrPBSE had showed 10-fold greater conversion efficacy for bovine PrPsen than for human codon 129-M (methionine) PrPsen and 30-fold greater conversion efficacy than for human codon 129-V (valine) PrPsen, while ovine PrPSc showed five-fold greater conversion efficacy for ovine PrPsen than for human 129-M PrPsen and eight-fold greater conversion than for human 129- V PrPsen (Raymond et al., 1997). 227. Results of recent work in transgenic mice expressing human PrP (see paragraph 71), in which transmission of CWD from elk by intracerebral inoculation failed, was considered to strongly suggest a species barrier to transmission of elk CWD to humans (Kong et al., 2004). CWD Review / Dr Debra Bourne / October 2004 / For SEAC / Page 48 of 66 Potential risk from consuming cervid products Velvet antler 228. Limited studies to date indicate risk from this product may be very low. No CWDspecific PrP accumulation was detected in a sample of velvet from an elk stag which developed clinical CWD about three months later; there were severe brain lesions and extensive CWD-specific PrP staining in both the brain and peripheral lymphoid tissue of the stag (Kahn et al., 2004). Consumption of venison and other parts of the animal 229. PrPCWD has not been detected in muscle tissue from infected cervids (Spraker et al., 2002c). However, it has been recommended by the World Health Organisation that no parts or products of any animal know to be CWD-positive should be consumed (WHO, 2000). Public health authorities in the USA and Canada have indicated agreement with this (Canadian Food Inspection Agency, 2003; Chronic Wasting Disease Alliance, 2004). It has been suggested that if a harvested cervid is being tested for CWD, the test results should be awaited before the meat is eaten (Wisconsin Department of Agriculture, Trade and Consumer Protection, 2002). Authorities in North America have widely advised that (a) tissues likely to contain the greatest amount of CWD agent in infected cervids, including the brain, spinal cord, lymph nodes, spleen, tonsils and eyes, should not be consumed from any harvested deer; (b) meat should be boned out and fat and connective tissue removed (which would also remove lymph nodes); and (c) hunters should avoid eating meat from deer or elk which look sick or which test positive for CWD (Buege, 2002; Chronic Wasting Disease Alliance, 2004; Williams et al., 2002; Wisconsin Department of Agriculture, Trade and Consumer Protection, 2002; Belay et al., 2004). Potential risk from handling and processing cervids 230. In order to minimise any potential risk from exposure to the agent of CWD, hunters, meat processors and taxidermists handling cervid carcasses are advised to wear latex or rubber gloves when handling or dressing cervids from CWD-endemic areas, to minimise handling of brain and spinal cord, and to thoroughly wash knives and other implements after use on deer or elk carcasses (Belay, 2004; Williams et al., 2002). It has been suggested that the risk of build-up of infectious CWD agent in a venison processing plant would be unlikely (Buege, 2002). Potential risk from disposal of carcasses and subsequent contamination of ground/water/air 231. In 2002 a risk analysis was produced on disposal of deer from Wisconsin in municipal solid landfills. It was noted that it is not known how much infected material a human (or animal) must consume or be exposed to in order to be infected with CWD. The report took into account the probable species barrier for transmission to humans (Raymond et al., 2000). It was noted that the CWD agent is hydrophobic and likely to adhere to organic materials within a landfill, taking several months to move through the landfill, and that any infectivity exiting the landfill would be captured in the landfill effluent. If effluent was transferred to a wastewater plant (rather than recirculated in the landfill) the agent would be expected to partition with the sludge fraction, which would be diluted greatly with other solids and mixed with nine inches (22.5 cm) of topsoil, providing an extremely large dilution factor. It was concluded that there was no significant risk to human health from disposing of deer infected with CWD in properly constructed landfill sites (Olander, 2002).
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FULL TEXT 66 PAGES ;
http://www.seac.gov.uk/papers/cwdiseaseannex1.pdf
1 Chronic wasting disease AND TISSUES THAT MIGHT CARRY A RISK FOR HUMAN FOOD AND ANIMAL FEED CHAINS REPORT 2 1 MANDATE..........................................................................................................................................
4 2 PREAMBLE........................................................................................................................................
4 3 CWD IN NORTH AMERICA ............................................................................................................
5 3.1 HISTORICAL PERSPECTIVE OF OCCURRENCE ......................................................................
5 3.1.1 CWD in captive and farmed cervidae......................................................................................
5 3.1.2 CWD in free-ranging cervidae ................................................................................................
6 3.2 NATURAL HOST RANGE..............................................................................................................
7 3.3 EXPERIMENTAL TRANSMISSIBILITY.......................................................................................
8 3.3.1 Transmissibility of CWD..........................................................................................................
9 3.3.1.1 Intracerebral inoculation studies:.......................................................................................................
9 3.3.1.2 Oral and other natural exposure route studies .................................................................................
10 3.3.2 Susceptibility of deer and elk to other TSEs ..........................................................................
11 3.4 EPIDEMIOLOGY..........................................................................................................................
11 3.4.1 Descriptive Epidemiological Features ..................................................................................
11 3.4.1.1 Chronology of distribution in the USA ...........................................................................................
11 3.4.1.2 Chronology of distribution in CANADA ........................................................................................
12 3.4.2 Evidence for lateral transmission ..........................................................................................
13 3.4.3 The origin of CWD.................................................................................................................
15 3.5 PATHOGENESIS..........................................................................................................................
16 3.5.1 Distribution of lesions / PrPCWD in clinically affected animals ..........................................
17 3.5.2 Studies of PrPCWD in pre-clinically infected animals..........................................................
18 3.5.2.1 Studies of PrPCWD in naturally exposed animals...........................................................................
18 3.5.2.2 Studies of PrPCWD in experimentally infected animals .................................................................
18 3.5.3 Conclusions ...........................................................................................................................
19 3.6 DIAGNOSIS ..................................................................................................................................
19 3.6.1 Clinical diagnosis of CWD....................................................................................................
19 3.6.2 Laboratory Diagnosis............................................................................................................
21 3.6.3 Laboratory diagnosis in live animals ....................................................................................
22 Mule deer and white-tailed deer......................................................................................................................
22 Elk..................................................................................................................................................................
22 3.7 SURVEILLANCE..........................................................................................................................
23 3.7.1 Type and organisation of surveillance in free-ranging cervids .............................................
23 3.7.1.1 USA................................................................................................................................................
23 3.7.1.2 Canada............................................................................................................................................
24 3.7.1.3 Planned surveillance on free ranging Cervidae in NA.....................................................................
24 3.7.2 Surveillance in farmed cervids ..............................................................................................
25 3.7.2.1 USA................................................................................................................................................
25 3.7.2.2 Canada............................................................................................................................................
26 3.8 CONTROL STRATEGIES.............................................................................................................
26 3.8.1 In the USA.............................................................................................................................
26 3.8.2 In Canada ..............................................................................................................................
28 3.8.3 Economic impact ...................................................................................................................
29 4 TSES IN CERVIDS IN EUROPE...................................................................................................
30 4.1 THE HISTORICAL AND CURRENT SITUATION IN GREAT BRITAIN IN RELATION TO BSE
30 4.2 PAST AND CURRENT SURVEILLANCE IN EUROPE .............................................................
31 5 POSSIBLE GLOBAL OCCURRENCE OF TSES IN FARMED CERVIDAE ...........................
33 6 FOOD AND FEED SAFETY AND HUMAN AND ANIMAL RISK ...........................................
34 6.1 FOOD SAFETY.............................................................................................................................
35 6.2 FEED SAFETY AND ANIMAL HEALTH ...................................................................................
36 6.3 CJD IN THE USA AND POSSIBLE RELEVANCE TO CWD.....................................................
36 7 RISK OF SPREAD TO EUROPE....................................................................................................
38 8 SUMMARY AND CONCLUSIONS.................................................................................................
39 8.1 SUMMARY...................................................................................................................................
39 8.2 CONCLUSIONS............................................................................................................................
40 9 BIBLIOGRAPHY.............................................................................................................................
41 10 ANNEXES .........................................................................................................................................
48
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36
6.3 CJD IN THE USA AND POSSIBLE RELEVANCE TO CWD
Recently, the Center for Disease Control (CDC) has issued a new statement concerning CWD and possible human infection: Although it is generally prudent to avoid consuming food derived from any animal with evidence of a TSE, to date, there is no evidence that CWD has been transmitted or can be transmitted to humans under natural conditions . However, the CDC has renewed surveillance efforts in order to rule out a link between CWD and vCJD. While, to date there has been one case of vCJD reported in US (contracted in the UK), the CDC is working with ongoing investigations in Wyoming and Colorado to track cases of CJD or suspected CJD.
37
CDC reported on the epidemiological investigations carried out on three patients who died of degenerative neurological illness during the period 1993-1999 and who were hunter and/or had a history of consuming venison during wild game feasts. All three patients were aged over 55 and developed neurological symptoms prior to death.
Sporadic CJD was confirmed in one case as the cause of death (CDC, 2003). Belay et al., (2001) Recent reports on of 3 unusually young CJD patients (aged 28, 28 and 30 years) who regularly consumed deer or elk meat, which created concern about the zoonotic transmission of CWD. Investigations, however, by CDC found that these were all cases of sporadic CJD of different types. In the USA the occurrence of CJD in persons 30 years or younger is rare (during 1979-1996, only 12 such CJD cases were reported to the CDC and 8 of these resulted from the use of contaminated growth hormone or dura maters grafts). Against the background of the occurrence and recognition of vCJD in 1996 it is difficult to make an epidemiological distinction between an increased incidence of CJD that might represent an indication of a novel exogenous source of infection and an increased ascertainment of CJD cases in young patients due to better surveillance. Belay et al., (2001), from the National Centre for Infectious Diseases have examined the hypothesis that a causal link could be made between the disease in these 3 patients and CWD. They reviewed medical records and interviewed family members and state wildlife and agriculture officials. Brain tissue samples were examined using histopathologic, immunohistochemical, immunoblotting, or prion gene analysis methods. The investigation assessed the presence or absence of CJD risk factors, associations with deer and elk hunting in CWD- enzootic areas and comparison of the evidence from the 3 patients with that of a zoonotic link between vCJD and bovine spongiform encephalopathy. None of the patients had established CJD risk factors or a history of travel to Europe. Two of the patients hunted game animals and one was a daughter of a hunter. Unlike patients with vCJD, the 3 patients did not express a common phenotype of the disease, which did not suggest a causal link between CWD and CJD (there was also heterogeneity among the three patients on the codon 129 : Met/Met, Val/Val and Met/Val respectively). Molecular phenotyping characteristics for the 2 patients studied gave type 1 on Western Blot according to Parchi et al.(1997), which differs from that of vCJD.
In conclusion, the CDC report on the CJD in the patients aged over 55 years and the investigation of Belay et al. (2001) related to the young CJD patients found no strong evidence for a causal link between CWD and CJD. Both, however, concluded as well that ongoing national surveillance for CJD and other neurological cases will remain important for continuing to assess the risk, if any, of CWD transmission to humans. Race et al., (2002) described abnormal PrP glycoforms of CWD in comparison to PrP from scrapie and BSE. Analysis of these abnormal PrP glycoform patterns from CWD affected deer and elk, scrapie-affected sheep and cattle and cattle with BSE failed to identify patterns capable of reliably distinguishing these transmissible spongiform encephalopathy diseases. However, PrP-res patterns sometimes differed among individual animals, suggesting the possibility of multiple CWD strains.
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40
8.2 CONCLUSIONS
With regard to the initial question of the mandate, a theoretical risk for prion transmission to humans consuming products of CWD affected-cervids of all ages in countries where CWD exists cannot be excluded. Similarly, transmission risk of prions to domestic animals cannot be excluded. There is therefore a scientific basis on which to exclude tissues from animals that carry a CWD risk, from human or animal feed chains.
However, the early and widespread involvement of tissues in CWD infected animals does not allow to define a SRM list, neither to define any lower age cut off as has been defined for cattle in relation to BSE. Neither is there sufficient knowledge to define exclusions or amendment of any SRM rule on the basis of relative genetic resistance to infection as has been proposed for sheep and goats in the event that evidence indicates the probable natural occurrence of BSE in these species 5.
Although available information indicates imports of live Cervidae from NA to EU and trade in meat products from cervid species as being negligible, it is important to reach certainty that no transfer of risk takes place through trade of live cervids and its derived products.
At present, there are no scientific data that CWD is occurring in Cervidae elsewhere than in those countries from which it has been previously reported. However, systematic TSE surveillance of cervid populations has either been absent or has only just started in European countries. Until results of such surveillance become available no conclusion can be drawn with regard to the occurrence of CWD or similar TSE in the cervid population of Europe.
snip...
http://europa.eu.int/comm/food/fs/sc/ssc/out324_en.pdf Report on the Deer Industry in Great Britain, 2002
http://www.seac.gov.uk/papers/munrodeerrptannex3.pdf
TSE SURVEILLANCE IN DEER
Background
1. Prior to the reinforced mammalian meat and bone meal ban, it is likely that deer in the UK and elsewhere in Europe were exposed to contaminated feed. Therefore, the possibility that BSE may be present in deer cannot be ruled out. Additionally, some deer species in North America are known to be affected by chronic wasting disease (CWD) a naturally occurring TSE.
2. Although there has been no reported evidence of TSE infection among deer in the EU, active surveillance is necessary to determine whether or not it is present. There is no current EU requirement for TSE surveillance in deer. However, it is likely that Member States may be required to initiate surveillance programmes in the future. In advance of this possible requirement, the VLA has conducted some small surveys to evaluate the tests. Other Member States have also conducted some TSE surveillance in deer.
UK surveys
3. In 2002, VLA obtained samples of whole carcases and viscera from 304 wild deer (189 roe, 66 fallow, 22 red and 13 muntjac deer as well as 14 samples from undetermined deer species). Most had been shot for human consumption but there were also some road kills. All had been submitted for TB testing. Samples, including brain, spleen, lymph node and Peyers Patch, from these cases were examined by immunohistochemistry using antibodies known to be able to detect CWD as well as those used in the UK for the detection of BSE and scrapie. Positive control samples of CWD from US deer and BSE from UK cattle were also included.
4. In 2003, a further 99 samples were collected from 52 roe, 33 fallow, 5 muntjac and 9 undetermined species of deer. In addition, to the immunohistochemical examination, these samples were also tested using the Biorad ELISA. No evidence of TSE was detected in any of the 403 deer examined in this survey.
5. A further survey of 1249 deer culled from Royal Parks (856 red and 393 fallow deer) was conducted from September to December 2003. All the samples were examined by immunohistochemistry using antibodies that recognise CWD and BSE and by the Biorad ELISA. No evidence of any TSE was detected.
6. A further survey of deer culled from the New Forest is now in progress. Surveys in other Member States
7. A number of other EU Member States have conducted surveys for TSEs in deer. The programmes vary considerably in their size and scope and, although the surveillance is limited, none have detected any evidence of TSE in deer. The available information from these surveillance studies is summarised in Table 1.
TABLE 1 Surveys of TSEs in deer in other EU Member States Country Period Number of animals (type/species) Test methods Germany 2001 1000 (Wild deer) Biorad, IHC 2002- 2004 > 4000 (Roe, red and fallow) Biorad, IHC 2004- 2005 Testing of 6000 planned Biorad, IHC Belgium 1997- 2003 38 (unknown) Histopathology, IHC, SAF. Biorad since 2001 Denmark 1999- 2002 6 (farmed fallow), 7 (wild roe), 3 (exotic) Italy 1999- 2004 18 (wild) Histopathology, IHC and western blot Finland 1999- 2002 5 (white tailed) 4 (unknown) 2003 900 (healthy reindeer) 3 (fallen reindeer) Biorad Sweden 2002- 2003 6 (moose) 2 (roe) IHC, histopathology. Biorad since 2003
TSS
############## BSE-L-subscribe-request@kaliv.uni-karlsruhe.de ##############
Saturday, July 16, 2016
Chronic wasting Disease in Deer (CWD or Spongiform Encephalopathy) The British Deer Society 07/04/2016
Red Deer Ataxia or Chronic Wasting Disease CWD TSE PRION?
could this have been cwd in the UK back in 1970’S ???
SEE FULL TEXT ;
Sunday, August 28, 2016
CONFIDENTIAL
Transmissible Spongiform Encephalopathy TSE Prion and how Politics and Greed by the Industry spread madcow type diseases from species to species and around the globe
TSE PRIONS AKA MAD COW TYPE DISEASE, LIONS AND TIGERS AND BEARS, OH MY!
Please be assured, the USA does NOT have any clue as to what the real perspective on the TSE prion disease in domestic feline and canine, much less our big wild cats, OR any other species including humans for that matter, but one thing for sure, the studies and history of the mad cow debacle below are deeply concerning with regards, to humans and wild big cats like mountain lions, cougars, lynx, Jaguar, and such, that feed on cervids that are infected with CWD. one thing for sure, don’t kid yourselves, all are very much susceptible to the TSE Prion disease, and if you don’t look, you don’t find, problems solved$$$
2017
-----Original Message-----
From: Terry Singeltary <flounder9@verizon.net>
To: bse-ll@lists.aegee.org>
Cc: cjdvoice <cjdvoice@yahoogroups.com>; bloodcjd <bloodcjd@yahoogroups.com>
Sent: Wed, Jul 26, 2017 10:52 am
Subject: Chronic wasting disease continues to spread Disease of cervids causing local population declines
From: Terry Singeltary <flounder9@verizon.net>
To: bse-l
Cc: cjdvoice <cjdvoice@yahoogroups.com>; bloodcjd <bloodcjd@yahoogroups.com>
Sent: Wed, Jul 26, 2017 10:52 am
Subject: Chronic wasting disease continues to spread Disease of cervids causing local population declines
August 15, 2017
Chronic wasting disease continues to spread
Disease of cervids causing local population declines
By Greg Cima Posted July 26, 2017
Mule deer in Wyoming (Courtesy of Wyoming Game and Fish Department) An always-fatal neurologic disease is contributing to declines in Western deer and elk herds and raising the possibility of local extinctions.
Bryan Richards, chronic wasting disease project leader within the U.S. Geological Survey's National Wildlife Health Center, has seen clear patterns of increasing spread and prevalence.
"Where it's established, it's spreading and growing," he said. "We have a lot of geographic areas with relatively recent detections, and we really do not have a very effective arsenal of tools with which to manage this disease once it becomes established in a free-ranging herd."
Where it is new, he said, "It looks more or less like one would expect if you drop disease at a focus on the landscape, and you have, over time, deer-to-deer-to-deer transmission."
Dr. Todd E. Cornish, a pathologist and associate professor who studies chronic wasting disease at the University of Wyoming, said two of his recent field studies show the disease has driven population declines among the mule deer and white-tailed deer studied. The article he co-authored on white-tailed deer, published a year ago August in the online scientific journal PLoS ONE (http://jav.ma/CWDdeer), described a 10 percent annual decline among deer in an area with a CWD prevalence of about 33 percent. His mule deer figures are pending publication.
Melia DeVivo, PhD, collared mule deer in southeastern Wyoming from 2010-14 to study CWD's effects, and she reported in her 2015 doctoral dissertation that the disease had caused significant declines in the herd studied.
In scenarios modeled for the dissertation, Dr. DeVivo and her co-authors found that the mule deer herd could be extinct within 41 years, although selection for a known genetic resilience to CWD could preserve a population about one-tenth the size of the original—several hundred deer—through the next 100 years. The minority of mule deer with that trait still acquire fatal infections but tend to live longer than others with CWD.
Where it's established, it's spreading and growing. We have a lot of geographic areas with relatively recent detections, and we really do not have a very effective arsenal of tools with which to manage this disease once it becomes established in a free-ranging herd."
Bryan Richards, chronic wasting disease project leader within the USGS National Wildlife Health Center
"While natural selection may not occur quickly enough to prevent a severe reduction of some cervid populations, the sustainability of a remnant population comprised of mostly less-susceptible genotyped deer remains to be determined," the dissertation states.
Richards said some genotypes in mule deer, white-tailed deer, and elk are categorized as resistant to CWD because, in wild, free-ranging populations, these animals seem to have lower infection rates and prolonged incubation periods. While a typical white-tailed deer could have a CWD incubation period of 18-24 months before clinical signs are seen, for example, a resistant deer could have an incubation period of 50-60 months, he said. But those deer also may shed infectious prions for a longer time.
The misfolded prion proteins responsible for CWD spread through saliva and waste. They are resistant to heat and ultraviolet light, and—like the prions that cause scrapie in sheep—they may remain viable for decades, Richards said. They also escape immune responses, so wildlife managers lack vaccines.
CWD prions are not known to cause infections in humans, but public health advisories recommend against eating meat of infected animals.
Adapted from a map by the U.S. Geological Survey's National Wildlife Health Center View larger
Difficult to control A state natural resource agency needs to detect CWD emergence soon after introduction to have a chance at eliminating it, Richards said. But state governments have reduced surveillance of cervids killed by hunters since the Department of Agriculture reduced its funding to states five years ago, he said.
Donna Karlsons, a spokeswoman for the Department of Agriculture's Animal and Plant Health Inspection Service, said APHIS ended its cooperative agreements supporting state-run CWD surveillance when appropriations to the agency declined in fiscal year 2012. APHIS had spent about $10 million in the preceding two fiscal years.
Congress appropriated $3.5 million to APHIS for all cervid health activities, including CWD, for the fiscal year ending this September, an increase from $3 million annually in the past several years, Karlsons said.
The Minnesota Department of Natural Resources is trying to eliminate the disease in Fillmore County in the state's southeast corner, where a cluster of 11 infections has been found in wild deer since the fall 2016 hunting season. Lou Cornicelli, PhD, wildlife research manager for the Minnesota DNR, said the infections could have emerged from three sources: illegal movement of a deer carcass, migration of a young male deer, or contact between wildlife and deer from a captive cervid farm with an unidentified infection.
Fillmore County alone has 23 of the state's 460 cervid farms, and at least two farms in other counties have CWD infections. Before the outbreak in fall 2016, Minnesota had found one CWD-positive wild deer, in 2010, also in the southeast and likely transmitted from a farm with infected captive elk, Dr. Cornicelli said.
Dr. Michael W. Miller, senior wildlife veterinarian for Colorado Parks and Wildlife, said surveillance is identifying CWD in new areas, most of them adjacent to where the disease is endemic.
"However, our surveillance efforts in recent years lack the intensity to assure the early detection of geographic extensions," he said. "Consequently, some of these 'new' foci were likely established some time ago but detected only recently."
Existing surveillance indicates one Colorado deer herd has had a decline in CWD prevalence since the state used sustained hunting and culling campaigns in the early 2000s, whereas other affected herds have had stable or increased prevalence, Dr. Miller said. Colorado Parks and Wildlife is gathering data to try to identify which hunter-based management strategies are most likely to stabilize or lower CWD prevalence. The state also is implementing required participation by hunters in some areas.
"Developing sustainable approaches for CWD management is a subject of keen interest among several western wildlife management agencies, so hopefully we'll be able to make progress on this in coming years," Dr. Miller said in a message.
University of Minnesota fish and wildlife students Breanna DiMartino (left) and Hailey Walters remove lymph nodes from a deer during chronic wasting disease surveillance in November 2016 in southeastern Minnesota. (Courtesy of Minnesota Department of Natural Resources) Wisconsin's Department of Natural Resources has been dealing with the disease for 15 years, and data show increases in prevalence and distribution there as well, said Tami Ryan, the DNR's Wildlife Health section chief. It is endemic in southern Wisconsin, and newer cases have been found in central Wisconsin and once in the northwest.
The state was aggressive the first five years, intending to eradicate the disease through all conceivable responses: expanded hunting, professional sharpshooting, and trapping and removal, she said. Prevalence declined where CWD-positive animals were removed.
But hunters became discouraged because they saw fewer deer, Ryan said. Public acceptance of those tools waned, and funding declined, so the department shifted to disease monitoring.
Some tools remain, such as special hunting seasons and a program requiring that hunters kill an antlerless deer to be allowed to shoot a buck. The state also works with a citizen advisory team on increasing participation in surveillance.
Dr. DeVivo, who now works for the Washington Department of Fish and Wildlife, said strong management practices, such as culling, are not viable for the Wyoming population she studied. The disease agent likely was circulating in the herd decades before it was identified there in the early 2000s, when prevalence was already at 15 percent, she said.
"The environmental contamination in that area is probably some of the highest that you'll see in any area, just because CWD has been there for so long, and we know that the environment does play a role with transmission," she said.
Herds in the area can have disease prevalence upward of 30 percent in female deer and 50 percent in males.
"Without any of those typical tools that you might employ for other diseases that we just don't have as a resource for this disease, our best tool right now, quite honestly, is continuing to study the disease in this population as well as continuing surveillance of the disease," Dr. DeVivo said.
"And some might find surveillance and research to be doing nothing, but it's doing a whole lot because this is an area where we have so much historic data already. To know exactly what it's doing now and into the future will only help us to get, possibly, somewhere with management."
Richards said his heart sank when he read an article (J Gen Virol 2006;87:3737-3740) that indicates the infectious agent of sheep scrapie can remain viable in an environment for at least 16 years, which he said has implications for the survival of CWD.
That article indicates a farm in Iceland had a scrapie outbreak in 1982, removed sheep from the barn until 1998, and experienced another outbreak in 2000. The authors wrote that epidemiologic investigation established "with near certitude" that the disease had not been introduced from outside the farm.
Dr. Mary Wood, Wyoming state wildlife veterinarian, said her agency will work with the public to find and test new strategies to manage CWD.
"Any management strategy that we try is going to be somewhat experimental in nature," she said.
Wyoming's surveillance indicates CWD is spreading westward, but Dr. Wood notes that the surveillance is imperfect, and CWD has uneven distribution even in herds with high prevalence. In a herd with low prevalence, it can be difficult to detect.
By the time CWD surveillance began in Wyoming's core endemic area, she said, prevalence there was higher than 10 percent.
Dr. Edward A. Hoover (right), a professor and infectious disease researcher at Colorado State University (Courtesy of Colorado State University) "We have certainly seen prevalence increase in those areas, and we've seen prevalences at 40 percent in some areas," Dr. Wood said. "And it does appear that, now, we're seeing other areas with an increase in prevalence as you look at the areas that surround our core endemic area."
While prevalence seems to be increasing, Dr. Wood needs larger sample sizes to know for certain. Wyoming, like many states, relies on diagnostic samples collected from cervids killed by hunters, most of them mule deer, followed by elk, white-tailed deer, and moose. Other samples come from roadkill and animals seen with clinical signs.
Answers are elusive CWD prions are amazing for their ability to spread as a virus would, through saliva, urine, and feces as well as contaminated environments, according to Dr. Edward A. Hoover, a professor and infectious disease researcher at Colorado State University. The Hoover laboratory's CWD research includes assay and vaccine development, although Dr. Hoover said the latter is a difficult prospect because of the lack of a known immune response to prion diseases.
A typical prion protein produced within an animal cell folds in a specific way, and a typical misfolded version is degraded through cellular editing, he said. Prion diseases result from misfolded prions that not only escape the editing mechanisms but also cause a zombie outbreak–like chain reaction among normal proteins within a cell, resulting in generations more of misfolded prions.
In terms of prion disease research, Dr. Hoover said understanding how misfolded prions cause this chain reaction would be like finding a holy grail.
The misfolded proteins escape the cell where they were created, enter other cells, cross mucous membranes, spread to other tissues such as those in the lymphoid system—where they replicate—and spread to the brain, Dr. Hoover said. In the case of CWD, they again spread across mucous membranes to infect other deer.
Yet, he thinks there may be a way to interrupt the disease process or spur an immune response without causing an autoimmune disease. Any such solutions could have implications for human neurologic diseases involving misfolded proteins, including Parkinson disease and Alzheimer disease.
Dr. Hoover also noted that, as far as we know, a species barrier is protecting humans from epidemics with CWD and scrapie, neither of which are known to infect a broad range of species as bovine spongiform encephalopathy can. But he also recommends caution since much about that barrier remains unknown.
Dr. Wood said that, while a vaccine candidate study was wrapping up at Wyoming's state wildlife research center, the results were not promising.
"We don't think that we have the ability, at least with the tools we have now, to eradicate the disease," Dr. Wood said. "So, our goal now is to try and figure out how to manage it to minimize its impact on our free-ranging deer and elk herds."
Developing sustainable approaches for CWD management is a subject of keen interest among several western wildlife management agencies, so hopefully we'll be able to make progress on this in coming years."
Dr. Michael W. Miller, senior wildlife veterinarian, Colorado Parks and Wildlife
Dr. Wood said that, even where the prevalence is 10 to 20 percent, CWD is affecting herds.
"I think it makes them less resilient and less able to bounce back after a harsh winter, less able to grow, less robust," she said. "And, so, even at lower prevalences, even if there's not a true decline in the population due to the disease, it still impacts that population, it still causes added mortality."
Dr. Cornish, of CSU, said applying any action across broad swaths of the CWD-endemic areas of Wyoming or Colorado, where deer, elk, and moose are vulnerable to the disease, would be daunting. He also noted that mule deer in particular are stressed by human development, droughts, and harsh winters.
A Minnesota DNR announcement about the state's disease response included a reminder that feeding wild deer, including providing salt or mineral blocks, is prohibited in the five counties of the state's southeastern tip to reduce deer congregation and disease transmission. Dr. Cornicelli said the state also prohibits scents or other lures that could entice deer to congregate within that disease management area, and it forbids movement of adult deer carcasses from that area, absent negative test results for CWD.
"We also have mandatory CWD testing that gives us the opportunity to define our prevalence, our change in prevalence, and also our spatial distribution of disease," he said.
An elk in Colorado (Courtesy of CSU) The Minnesota DNR also is trying to gain funding for research on deer movement patterns.
"Most of us who work in this profession—deal with big game populations and wildlife disease—don't want to live in a world where CWD is on the landscape 100 or 200 years from now," he said. "I think we're starting to see these population-level effects in the Western states that have had the disease for 50 years, we're starting to see these big increases in prevalence in Wisconsin, so they're, ultimately, going to have a population-level effect on deer, and we're doing what we can to hold back that tide."
Dr. Cornicelli expects surveillance will find more CWD infections, but he hopes to see a decline.
"If we can knock it back to seven and then, the next year, it's four, and then it's two, and then we don't find it for three years, then I think we're in good shape," he said. "But, if we find 13 next year scattered 20 miles away, then I'll have a completely different attitude."
Related JAVMA content: First successful CWD vaccine tested in deer (Feb. 15, 2015)
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
Subject: PRION 2017 CONFERENCE DECIPHERING NEURODEGENERATIVE DISORDERS VIDEO
PRION 2017 CONFERENCE DECIPHERING NEURODEGENERATIVE DISORDERS
PRION 2017 CONFERENCE VIDEO
Chronic Wasting Disease CWD TSE Prion to Humans, who makes that final call, when, or, has it already happened?
SATURDAY, JULY 29, 2017
Risk Advisory Opinion: Potential Human Health Risks from Chronic Wasting Disease CFIA, PHAC, HC (HPFB and FNIHB), INAC, Parks Canada, ECCC and AAFC
TUESDAY, JUNE 13, 2017
PRION 2017 CONFERENCE ABSTRACT First evidence of intracranial and peroral transmission of Chronic Wasting Disease (CWD) into Cynomolgus macaques: a work in progress
TUESDAY, JULY 04, 2017
*** PRION 2017 CONFERENCE ABSTRACTS ON CHRONIC WASTING DISEASE CWD TSE PRION ***
TUESDAY, JUNE 13, 2017
PRION 2017 CONFERENCE ABSTRACT Chronic Wasting Disease in European moose is associated with PrPSc features different from North American CWD
URINE
SUNDAY, JULY 16, 2017
*** Temporal patterns of chronic wasting disease prion excretion in three cervid species ***
WDA 2016 NEW YORK
We found that CWD adapts to a new host more readily than BSE and that human PrP was unexpectedly prone to misfolding by CWD prions. In addition, we investigated the role of specific regions of the bovine, deer and human PrP protein in resistance to conversion by prions from another species. We have concluded that the human protein has a region that confers unusual susceptibility to conversion by CWD prions.
Student Presentations Session 2
The species barriers and public health threat of CWD and BSE prions
Ms. Kristen Davenport1, Dr. Davin Henderson1, Dr. Candace Mathiason1, Dr. Edward Hoover1 1Colorado State University
Chronic wasting disease (CWD) is spreading rapidly through cervid populations in the USA. Bovine spongiform encephalopathy (BSE, mad cow disease) arose in the 1980s because cattle were fed recycled animal protein. These and other prion diseases are caused by abnormal folding of the normal prion protein (PrP) into a disease causing form (PrPd), which is pathogenic to nervous system cells and can cause subsequent PrP to misfold. CWD spreads among cervids very efficiently, but it has not yet infected humans. On the other hand, BSE was spread only when cattle consumed infected bovine or ovine tissue, but did infect humans and other species. The objective of this research is to understand the role of PrP structure in cross-species infection by CWD and BSE. To study the propensity of each species’ PrP to be induced to misfold by the presence of PrPd from verious species, we have used an in vitro system that permits detection of PrPd in real-time. We measured the conversion efficiency of various combinations of PrPd seeds and PrP substrate combinations. We observed the cross-species behavior of CWD and BSE, in addition to feline-adapted CWD and BSE. We found that CWD adapts to a new host more readily than BSE and that human PrP was unexpectedly prone to misfolding by CWD prions. In addition, we investigated the role of specific regions of the bovine, deer and human PrP protein in resistance to conversion by prions from another species. We have concluded that the human protein has a region that confers unusual susceptibility to conversion by CWD prions. CWD is unique among prion diseases in its rapid spread in natural populations. BSE prions are essentially unaltered upon passage to a new species, while CWD adapts to the new species. This adaptation has consequences for surveillance of humans exposed to CWD.
Wildlife Disease Risk Communication Research Contributes to Wildlife Trust Administration Exploring perceptions about chronic wasting disease risks among wildlife and agriculture professionals and stakeholders
Ms. Alyssa Wetterau1, Dr. Krysten Schuler1, Dr. Elizabeth Bunting1, Dr. Hussni Mohammed1 1Cornell University
Chronic wasting disease (CWD) is a fatal disease of North American Cervidae. New York State (NYS, USA) successfully managed an outbreak of CWD in 2005 in both captive and wild white-tailed deer (Odocoileus virginianus) with no reoccurrence of the disease as of 2015. To attain maximum compliance and efficacy of management actions for prevention of CWD entry, understanding the varied risk perceptions will allow for targeted, proactive communication efforts to address divergences between expert-derived risk assessments and stakeholder risk perceptions. We examined perceived risks associated with CWD introduction and exposure among agricultural and wildlife agency professionals within and outside of NYS, as well as stakeholder groups (e.g., hunters and captive cervid owners). We measured perceived risk using a risk assessment questionnaire online via Qualtrics survey software and evaluated similarities within, as well as differences in, perception among participant groups. New York State biologists employed by the Department of Environmental Conservation and independent non-NYS wildlife and agricultural professionals thought CWD risks associated with captive cervids were high; captive cervid owners thought risks for wild and captive cervids were low. Agriculture and wildlife professional groups agreed on general risk perceptions. We ranked 15 individual risk hazards into high and low medium categories based on all responses. Differences between groups were most evident in hypothetical disease pathways. Any pathway involving inter-state import of live cervids received high ranking for all groups except captive cervid owners. Comparatively low risk perceptions by captive cervid operators may stem from misinformation, lack of understanding of testing programs, and indemnity payments for animal depopulation. Communication and education directed at areas of disagreement may facilitate effective disease prevention and management.
MONDAY, JULY 17, 2017
National Scrapie Eradication Program May 2017 Monthly Report Fiscal Year 2017
TUESDAY, JULY 18, 2017
MINK FARMING USA TRANSMISSIBLE MINK ENCEPHALOPATHY TSE PRION DISEASE SURVEILLANCE AND TESTING
PAGE 25
Transmission Studies
Mule deer transmissions of CWD were by intracerebral inoculation and compared with natural cases 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 inoculam (?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.
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).***
Molecular Barriers to Zoonotic Transmission of Prions
*** chronic wasting disease, there was no absolute barrier to conversion of the human prion protein.
*** Furthermore, the form of human PrPres produced in this in vitro assay when seeded with CWD, resembles that found in the most common human prion disease, namely sCJD of the MM1 subtype.
*** 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). ***
*** 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). ***
*** 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 ;
you can see more evidence here ;
*** WDA 2016 NEW YORK ***
We found that CWD adapts to a new host more readily than BSE and that human PrP was unexpectedly prone to misfolding by CWD prions.
In addition, we investigated the role of specific regions of the bovine, deer and human PrP protein in resistance to conversion by prions from another species.
We have concluded that the human protein has a region that confers unusual susceptibility to conversion by CWD prions.
Student Presentations Session 2
The species barriers and public health threat of CWD and BSE prions
Ms. Kristen Davenport1, Dr. Davin Henderson1, Dr. Candace Mathiason1, Dr. Edward Hoover1 1Colorado State University
Chronic wasting disease (CWD) is spreading rapidly through cervid populations in the USA. Bovine spongiform encephalopathy (BSE, mad cow disease) arose in the 1980s because cattle were fed recycled animal protein. These and other prion diseases are caused by abnormal folding of the normal prion protein (PrP) into a disease causing form (PrPd), which is pathogenic to nervous system cells and can cause subsequent PrP to misfold. CWD spreads among cervids very efficiently, but it has not yet infected humans. On the other hand, BSE was spread only when cattle consumed infected bovine or ovine tissue, but did infect humans and other species. The objective of this research is to understand the role of PrP structure in cross-species infection by CWD and BSE. To study the propensity of each species’ PrP to be induced to misfold by the presence of PrPd from verious species, we have used an in vitro system that permits detection of PrPd in real-time. We measured the conversion efficiency of various combinations of PrPd seeds and PrP substrate combinations. We observed the cross-species behavior of CWD and BSE, in addition to feline-adapted CWD and BSE. We found that CWD adapts to a new host more readily than BSE and that human PrP was unexpectedly prone to misfolding by CWD prions. In addition, we investigated the role of specific regions of the bovine, deer and human PrP protein in resistance to conversion by prions from another species.
***We have concluded that the human protein has a region that confers unusual susceptibility to conversion by CWD prions.
CWD is unique among prion diseases in its rapid spread in natural populations. BSE prions are essentially unaltered upon passage to a new species, while CWD adapts to the new species. This adaptation has consequences for surveillance of humans exposed to CWD.
Wildlife Disease Risk Communication Research Contributes to Wildlife Trust Administration Exploring perceptions about chronic wasting disease risks among wildlife and agriculture professionals and stakeholders
PRION 2016 TOKYO
Zoonotic Potential of CWD Prions: An Update
Chronic wasting disease (CWD) is a widespread and highly transmissible prion disease in free-ranging and captive cervid species in North America. The zoonotic potential of CWD prions is a serious public health concern, but the susceptibility of human CNS and peripheral organs to CWD prions remains largely unresolved. We reported earlier that peripheral and CNS infections were detected in transgenic mice expressing human PrP129M or PrP129V. Here we will present an update on this project, including evidence for strain dependence and influence of cervid PrP polymorphisms on CWD zoonosis as well as the characteristics of experimental human CWD prions.
PRION 2016 TOKYO In Conjunction with Asia Pacific Prion Symposium 2016 PRION 2016 Tokyo Prion 2016
Cervid to human prion transmission
Kong, Qingzhong
Case Western Reserve University, Cleveland, OH, United States
Abstract
Prion disease is transmissible and invariably fatal. Chronic wasting disease (CWD) is the prion disease affecting deer, elk and moose, and it is a widespread and expanding epidemic affecting 22 US States and 2 Canadian provinces so far. CWD poses the most serious zoonotic prion transmission risks in North America because of huge venison consumption (>6 million deer/elk hunted and consumed annually in the USA alone), significant prion infectivity in muscles and other tissues/fluids from CWD-affected cervids, and usually high levels of individual exposure to CWD resulting from consumption of the affected animal among often just family and friends. However, we still do not know whether CWD prions can infect humans in the brain or peripheral tissues or whether clinical/asymptomatic CWD zoonosis has already occurred, and we have no essays to reliably detect CWD infection in humans. We hypothesize that:
(1) The classic CWD prion strain can infect humans at low levels in the brain and peripheral lymphoid tissues;
(2) The cervid-to-human transmission barrier is dependent on the cervid prion strain and influenced by the host (human) prion protein (PrP) primary sequence;
(3) Reliable essays can be established to detect CWD infection in humans; and
(4) CWD transmission to humans has already occurred. We will test these hypotheses in 4 Aims using transgenic (Tg) mouse models and complementary in vitro approaches.
Aim 1 will prove that the classical CWD strain may infect humans in brain or peripheral lymphoid tissues at low levels by conducting systemic bioassays in a set of "humanized" Tg mouse lines expressing common human PrP variants using a number of CWD isolates at varying doses and routes. Experimental "human CWD" samples will also be generated for Aim 3.
Aim 2 will test the hypothesis that the cervid-to-human prion transmission barrier is dependent on prion strain and influenced by the host (human) PrP sequence by examining and comparing the transmission efficiency and phenotypes of several atypical/unusual CWD isolates/strains as well as a few prion strains from other species that have adapted to cervid PrP sequence, utilizing the same panel of humanized Tg mouse lines as in Aim 1.
Aim 3 will establish reliable essays for detection and surveillance of CWD infection in humans by examining in details the clinical, pathological, biochemical and in vitro seeding properties of existing and future experimental "human CWD" samples generated from Aims 1-2 and compare them with those of common sporadic human Creutzfeldt-Jakob disease (sCJD) prions.
Aim 4 will attempt to detect clinical CWD-affected human cases by examining a significant number of brain samples from prion-affected human subjects in the USA and Canada who have consumed venison from CWD-endemic areas utilizing the criteria and essays established in Aim 3. The findings from this proposal will greatly advance our understandings on the potential and characteristics of cervid prion transmission in humans, establish reliable essays for CWD zoonosis and potentially discover the first case(s) of CWD infection in humans.
Public Health Relevance There are significant and increasing human exposure to cervid prions because chronic wasting disease (CWD, a widespread and highly infectious prion disease among deer and elk in North America) continues spreading and consumption of venison remains popular, but our understanding on cervid-to-human prion transmission is still very limited, raising public health concerns. This proposal aims to define the zoonotic risks of cervid prions and set up and apply essays to detect CWD zoonosis using mouse models and in vitro methods. The findings will greatly expand our knowledge on the potentials and characteristics of cervid prion transmission in humans, establish reliable essays for such infections and may discover the first case(s) of CWD infection in humans.
Key Molecular Mechanisms of TSEs
Zabel, Mark D.
Colorado State University-Fort Collins, Fort Collins, CO, United States
Abstract Prion diseases, or transmissible spongiform encephalopathies (TSEs), are fatal neurodegenerative diseases affecting humans, cervids, bovids, and ovids. The absolute requirement of PrPC expression to generate prion diseases and the lack of instructional nucleic acid define prions as unique infectious agents. Prions exhibit species-specific tropism, inferring that unique prion strains exist that preferentially infct certain host species and confront transmission barriers to heterologous host species. However, transmission barriers are not absolute. Scientific consensus agrees that the sheep TSE scrapie probably breached the transmission barrier to cattle causing bovine spongiform encephalopathy that subsequently breached the human transmission barrier and likely caused several hundred deaths by a new-variant form of the human TSE Creutzfeldt-Jakob disease in the UK and Europe. The impact to human health, emotion and economies can still be felt in areas like farming, blood and organ donations and the threat of a latent TSE epidemic. This precedent raises the real possibility of other TSEs, like chronic wasting disease of cervids, overcoming similar human transmission barriers. A groundbreaking discovery made last year revealed that mice infected with heterologous prion strains facing significant transmission barriers replicated prions far more readily in spleens than brains6. Furthermore, these splenic prions exhibited weakened transmission barriers and expanded host ranges compared to neurogenic prions. These data question conventional wisdom of avoiding neural tissue to avoid prion xenotransmission, when more promiscuous prions may lurk in extraneural tissues. Data derived from work previously funded by NIH demonstrate that Complement receptors CD21/35 bind prions and high density PrPC and differentially impact prion disease depending on the prion isolate or strain used. Recent advances in live animal and whole organ imaging have led us to generate preliminary data to support novel, innovative approaches to assessing prion capture and transport. We plan to test our unifying hypothesis for this proposal that CD21/35 control the processes of peripheral prion capture, transport, strain selection and xenotransmission in the following specific aims.
1. Assess the role of CD21/35 in splenic prion strain selection and host range expansion.
2. Determine whether CD21/35 and C1q differentially bind distinct prion strains
3. Monitor the effects of CD21/35 on prion trafficking in real time and space
4. Assess the role of CD21/35 in incunabular prion trafficking
Public Health Relevance Transmissible spongiform encephalopathies, or prion diseases, are devastating illnesses that greatly impact public health, agriculture and wildlife in North America and around the world. The impact to human health, emotion and economies can still be felt in areas like farming, blood and organ donations and the threat of a latent TSE epidemic. This precedent raises the real possibility of other TSEs, like chronic wasting disease (CWD) of cervids, overcoming similar human transmission barriers. Early this year Canada reported its first case of BSE in over a decade audits first case of CWD in farmed elk in three years, underscoring the need for continued vigilance and research. Identifying mechanisms of transmission and zoonoses remains an extremely important and intense area of research that will benefit human and other animal populations.
PMCA Detection of CWD Infection in Cervid and Non-Cervid Species
Hoover, Edward Arthur
Colorado State University-Fort Collins, Fort Collins, CO, United States
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).***
Molecular Barriers to Zoonotic Transmission of Prions
*** chronic wasting disease, there was no absolute barrier to conversion of the human prion protein.
*** Furthermore, the form of human PrPres produced in this in vitro assay when seeded with CWD, resembles that found in the most common human prion disease, namely sCJD of the MM1 subtype.
SPONTANEOUS ATYPICAL BOVINE SPONGIFORM ENCEPHALOPATHY
***Moreover, sporadic disease has never been observed in breeding colonies or primate research laboratories, most notably among hundreds of animals over several decades of study at the National Institutes of Health25, and in nearly twenty older animals continuously housed in our own facility.***
Envt.07:
Pathological Prion Protein (PrPTSE) in Skeletal Muscles of Farmed and Free Ranging White-Tailed Deer Infected with Chronic Wasting Disease
***The presence and seeding activity of PrPTSE in skeletal muscle from CWD-infected cervids suggests prevention of such tissue in the human diet as a precautionary measure for food safety, pending on further clarification of whether CWD may be transmissible to humans.
Yet, it has to be noted that our assessments of PrPTSE levels in skeletal muscles were based on findings in presumably pre- or subclinically infected animals. Therefore, the concentration of PrPTSE in skeletal muscles of WTD with clinically manifest CWD may possibly exceed our estimate which refers to clinically inconspicuous animals that are more likely to enter the human food chain. Our tissue blot findings in skeletal muscles from CWD-infected WTD would be consistent with an anterograde spread of CWD prions via motor nerve fibres to muscle tissue (figure 4A). Similar neural spreading pathways of muscle infection were previously found in hamsters orally challenged with scrapie [28] and suggested by the detection of PrPTSE in muscle fibres and muscle-associated nerve fascicles of clinically-ill non-human primates challenged with BSE prions [29]. Whether the absence of detectable PrPTSE in myofibers observed in our study is a specific feature of CWD in WTD, or was due to a pre- or subclinical stage of infection in the examined animals, remains to be established. In any case, our observations support previous findings suggesting the precautionary prevention of muscle tissue from CWD-infected WTD in the human diet, and highlight the need to comprehensively elucidate of whether CWD may be transmissible to humans. While the understanding of TSEs in cervids has made substantial progress during the past few years, the assessment and management of risks possibly emanating from prions in skeletal muscles of CWD-infected cervids requires further research.
Prions in Skeletal Muscles of Deer with Chronic Wasting Disease
Rachel C. Angers1,*, Shawn R. Browning1,*,†, Tanya S. Seward2, Christina J. Sigurdson4,‡, Michael W. Miller5, Edward A. Hoover4, Glenn C. Telling1,2,3,§ + Author Affiliations
1 Department of Microbiology, Immunology and Molecular Genetics, University of Kentucky, Lexington, KY 40536, USA. 2 Sanders Brown Center on Aging, University of Kentucky, Lexington, KY 40536, USA. 3 Department of Neurology, University of Kentucky, Lexington, KY 40536, USA. 4 Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO 80523, USA. 5 Colorado Division of Wildlife, Wildlife Research Center, Fort Collins, CO 80526, USA. ↵§ To whom correspondence should be addressed. E-mail: gtell2@uky.edu ↵* These authors contributed equally to this work.
↵† Present address: Department of Infectology, Scripps Research Institute, 5353 Parkside Drive, RF-2, Jupiter, FL 33458, USA.
↵‡ Present address: Institute of Neuropathology, University of Zurich, Schmelzbergstrasse 12, 8091 Zurich, Switzerland.
Abstract The emergence of chronic wasting disease (CWD) in deer and elk in an increasingly wide geographic area, as well as the interspecies transmission of bovine spongiform encephalopathy to humans in the form of variant Creutzfeldt Jakob disease, have raised concerns about the zoonotic potential of CWD. Because meat consumption is the most likely means of exposure, it is important to determine whether skeletal muscle of diseased cervids contains prion infectivity. 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.
Exotic Meats USA Announces Urgent Statewide Recall of Elk Tenderloin Because It May Contain Meat Derived From An Elk Confirmed To Have Chronic Wasting Disease
Contact: Exotic Meats USA 1-800-680-4375
FOR IMMEDIATE RELEASE -- February 9, 2009 -- Exotic Meats USA of San Antonio, TX is initiating a voluntary recall of Elk Tenderloin because it may contain meat derived from an elk confirmed to have Chronic Wasting Disease (CWD). The meat with production dates of December 29, 30 and 31, 2008 was purchased from Sierra Meat Company in Reno, NV. The infected elk came from Elk Farm LLC in Pine Island, MN and was among animals slaughtered and processed at USDA facility Noah’s Ark Processors LLC.
Chronic Wasting Disease (CWD) is a fatal brain and nervous system disease found in elk and deer. The disease is caused by an abnormally shaped protein called a prion, which can damage the brain and nerves of animals in the deer family. Currently, it is believed that the prion responsible for causing CWD in deer and elk is not capable of infecting humans who eat deer or elk contaminated with the prion, but the observation of animal-to-human transmission of other prion-mediated diseases, such as bovine spongiform encephalopathy (BSE), has raised a theoretical concern regarding the transmission of CWD from deer or elk to humans. At the present time, FDA believes the risk of becoming ill from eating CWD-positive elk or deer meat is remote. However, FDA strongly advises consumers to return the product to the place of purchase, rather than disposing of it themselves, due to environmental concerns.
Exotic Meats USA purchased 1 case of Elk Tenderloins weighing 16.9 lbs. The Elk Tenderloin was sold from January 16 – 27, 2009. The Elk Tenderloins was packaged in individual vacuum packs weighing approximately 3 pounds each. A total of six packs of the Elk Tenderloins were sold to the public at the Exotic Meats USA retail store. Consumers who still have the Elk Tenderloins should return the product to Exotic Meats USA at 1003 NE Loop 410, San Antonio, TX 78209. Customers with concerns or questions about the Voluntary Elk Recall can call 1-800-680-4375. The safety of our customer has always been and always will be our number one priority.
Exotic Meats USA requests that for those customers who have products with the production dates in question, do not consume or sell them and return them to the point of purchase. Customers should return the product to the vendor. The vendor should return it to the distributor and the distributor should work with the state to decide upon how best to dispose. If the consumer is disposing of the product he/she should consult with the local state EPA office.
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COLORADO: Farmer's market meat recalled after testing positive for CWD
24.dec.08 9News.com Jeffrey Wolf
Elk meat that was sold at a farmer's market is being recalled because tests show it was infected with chronic wasting disease. The Boulder County Health Department and Colorado Department of Public Health and Environment issued the recall Wednesday after the meat was sold at the Boulder County Fairgrounds on Dec. 13. Although there isn't any human health risk connected with CWD, the recalled was issued as a precaution. About 15 elk were bought from a commercial ranch in Colorado in early December and processed at a licensed plant. All 15 were tested for CWD and one came up positive. The labeling on the product would have the following information: *Seller: High Wire Ranch *The type of cut: "chuck roast," "arm roast," "flat iron," "ribeye steak," "New York steak," "tenderloin," "sirloin tip roast," "medallions" or "ground meat." *Processor: Cedaredge Processing *The USDA triangle containing the number "34645" People with questions about this meat can contact John Pape, epidemiologist at the Colorado Department of Public Health and Environment at 303-692-2628.
COULD NOT FIND any warning or recalls on these two sites confirming their recall of CWD infected meat. ...TSS
Wednesday, April 06, 2011
Presence and Seeding Activity of Pathological Prion Protein (PrPTSE) in Skeletal Muscles of White-Tailed Deer Infected with Chronic Wasting Disease
Prion Infectivity in Fat of Deer with Chronic Wasting Disease
Brent Race,# Kimberly Meade-White,# Richard Race, and Bruce Chesebro* Rocky Mountain Laboratories, 903 South 4th Street, Hamilton, Montana 59840
Received 2 June 2009/ Accepted 24 June 2009
ABSTRACT Top ABSTRACT TEXT REFERENCES
Chronic wasting disease (CWD) is a neurodegenerative prion disease of cervids. Some animal prion diseases, such as bovine spongiform encephalopathy, can infect humans; however, human susceptibility to CWD is unknown. In ruminants, prion infectivity is found in central nervous system and lymphoid tissues, with smaller amounts in intestine and muscle. 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.
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The highest risk of human contact with CWD might be through exposure to high-titer CNS tissue through accidental skin cuts or corneal contact at the time of harvest and butchering. However, the likelihood of a human consuming fat infected with a low titer of the CWD agent is much higher. It is impossible to remove all the fat present within muscle tissue, and fat consumption is inevitable when eating meat. Of additional concern is the fact that meat from an individual deer harvested by a hunter is typically consumed over multiple meals by the same group of people. These individuals would thus have multiple exposures to the CWD agent over time, which might increase the chance for transfer of infection.
In the Rocky Mountain region of North America, wild deer are subject to predation by wolves, coyotes, bears, and mountain lions. Although canines such as wolves and coyotes are not known to be susceptible to prion diseases, felines definitely are susceptible to BSE (9) and might also be infected by the CWD agent. Deer infected with the CWD agent are more likely to be killed by predators such as mountain lions (11). Peripheral tissues, including lymph nodes, muscle, and fat, which harbor prion infectivity are more accessible for consumption than CNS tissue, which has the highest level of infectivity late in disease. Therefore, infectivity in these peripheral tissues may be important in potential cross-species CWD transmissions in the wild.
The present finding of CWD infectivity in deer fat tissue raises the possibility that prion infectivity might also be found in fat tissue of other infected ruminants, such as sheep and cattle, whose fat and muscle tissues are more widely distributed in both the human and domestic-animal food chains. Although the infectivity in fat tissues is low compared to that in the CNS, there may be significant differences among species and between prion strains. Two fat samples from BSE agent-infected cattle were reported to be negative by bioassay in nontransgenic RIII mice (3, 6). However, RIII mice are 10,000-fold-less sensitive to BSE agent infection than transgenic mice expressing bovine PrP (4). It would be prudent to carry out additional infectivity assays on fat from BSE agent-infected cattle and scrapie agent-infected sheep using appropriate transgenic mice or homologous species to determine the risk from these sources.
*** 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 (216-119-163-189.ipset45.wt.net)
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.
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*** twenty-seven CJD patients who regularly consumed venison were reported to the Surveillance Center***,
snip... full text ;
In Confidence - Perceptions of unconventional slow virus diseases of animals in the USA - APRIL-MAY 1989 - G A H Wells
3. Prof. A. Robertson gave a brief account of BSE. The US approach was to accord it a very low profile indeed. Dr. A Thiermann showed the picture in the ''Independent'' with cattle being incinerated and thought this was a fanatical incident to be avoided in the US at all costs. ...
snip...see full text ;
Evidence That Transmissible Mink Encephalopathy Results from Feeding Infected Cattle Over the next 8-10 weeks, approximately 40% of all the adult mink on the farm died from TME. snip... The rancher was a ''dead stock'' feeder using mostly (>95%) downer or dead dairy cattle...
In Confidence - Perceptions of unconventional slow virus diseases of animals in the USA - APRIL-MAY 1989 - G A H Wells 3. Prof. A. Robertson gave a brief account of BSE. The US approach was to accord it a very low profile indeed. Dr. A Thiermann showed the picture in the ''Independent'' with cattle being incinerated and thought this was a fanatical incident to be avoided in the US at all costs. ...
The occurrence of CWD must be viewed against the contest of the locations in which it occurred. It was an incidental and unwelcome complication of the respective wildlife research programmes. Despite it’s subsequent recognition as a new disease of cervids, therefore justifying direct investigation, no specific research funding was forthcoming. The USDA veiwed it as a wildlife problem and consequently not their province! ...page 26.
*** Spraker suggested an interesting explanation for the occurrence of CWD. The deer pens at the Foot Hills Campus were built some 30-40 years ago by a Dr. Bob Davis. At or abut that time, allegedly, some scrapie work was conducted at this site. When deer were introduced to the pens they occupied ground that had previously been occupied by sheep.
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 item Kunkle, Robert item Kondru, Naveen item Manne, Sireesha item Smith, Jodi item Kanthasamy, Anumantha item West Greenlee, M 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 challenge="" groups="" month="" pigs="" remaining="" the="">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 5="" 6="" at="" by="" detected="" eia.="" examined="" group="" in="" intracranial="" least="" lymphoid="" month="" months="" of="" one="" pigs="" positive="" prpsc="" quic="" the="" tissues="" was="">6 months group, 5/6 pigs in the oral <6 4="" and="" group="" months="" 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.
CONFIDENTIAL
EXPERIMENTAL PORCINE SPONGIFORM ENCEPHALOPATHY
While this clearly is a cause for concern we should not jump to the conclusion that this means that pigs will necessarily be infected by bone and meat meal fed by the oral route as is the case with cattle. ...
we cannot rule out the possibility that unrecognised subclinical spongiform encephalopathy could be present in British pigs though there is no evidence for this: only with parenteral/implantable pharmaceuticals/devices is the theoretical risk to humans of sufficient concern to consider any action.
Our records show that while some use is made of porcine materials in medicinal products, the only products which would appear to be in a hypothetically ''higher risk'' area are the adrenocorticotrophic hormone for which the source material comes from outside the United Kingdom, namely America China Sweden France and Germany. The products are manufactured by Ferring and Armour. A further product, ''Zenoderm Corium implant'' manufactured by Ethicon, makes use of porcine skin - which is not considered to be a ''high risk'' tissue, but one of its uses is described in the data sheet as ''in dural replacement''. This product is sourced from the United Kingdom.....
snip...see much more here ;
WEDNESDAY, APRIL 05, 2017
Disease-associated prion protein detected in lymphoid tissues from pigs challenged with the agent of chronic wasting disease
TUESDAY, APRIL 18, 2017
*** EXTREME USA FDA PART 589 TSE PRION FEED LOOP HOLE STILL EXIST, AND PRICE OF POKER GOES UP ***
TUESDAY, MARCH 28, 2017
*** Passage of scrapie to deer results in a new phenotype upon return passage to sheep ***
MONDAY, MARCH 13, 2017
CHRONIC WASTING DISEASE CWD TSE PRION UDATE March 13, 2017
SATURDAY, JANUARY 14, 2017
CHRONIC WASTING DISEASE CWD TSE PRION GLOBAL UPDATE JANUARY 14, 2017
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.
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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.
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What is the risk of chronic wasting disease being introduced into Great Britain? A Qualitative Risk Assessment October 2012
Thursday, April 07, 2016
What is the risk of chronic wasting disease being introduced into Great Britain? An updated Qualitative Risk Assessment March 2016
Subject: DEFRA What is the risk of a cervid TSE being introduced from Norway into Great Britain? Qualitative Risk Assessment September 2016
Friday, September 30, 2016
DEFRA What is the risk of a cervid TSE being introduced from Norway into Great Britain? Qualitative Risk Assessment September 2016
Scientific Opinion
Chronic wasting disease (CWD) in cervids
Authors
EFSA Panel on Biological Hazards (BIOHAZ),
First published: 18 January 2017Full publication history
DOI: 10.2903/j.efsa.2017.4667View/save citation
TUESDAY, JUNE 20, 2017
Norway Confirms 6th Case of Skrantesjuke CWD TSE Prion Disease
Tuesday, December 13, 2016
Norway Chronic Wasting Disease CWD TSE Prion disease Skrantesjuke December 2016 Update
Thursday, September 22, 2016
NORWAY DETECTS 5TH CASE OF CHRONIC WASTING DISEASE CWD TSE PRION Skrantesjuke
Saturday, September 03, 2016
NORWAY Regulation concerning temporary measures to reduce the spread of Chronic Wasting Disease (CWD) as 4th case of skrantesjuke confirmed in Sogn og Fjordane
Wednesday, August 31, 2016
*** NORWAY CONFIRMS 4TH CASE OF CHRONIC WASTING DISEASE CWD TSE PRION IN SECOND CARIBOU
Wednesday, August 31, 2016
NORWAY CONFIRMS 4TH CASE OF CHRONIC WASTING DISEASE CWD TSE PRION IN SECOND CARIBOU
Tuesday, August 02, 2016
Chronic wasting disease of deer – is the battle to keep Europe free already lost?
Tuesday, June 14, 2016
*** Chronic Wasting Disease (CWD) in a moose from Selbu in Sør-Trøndelag Norway ***
Thursday, July 07, 2016
Norway reports a third case Chronic Wasting Disease CWD TSE Prion in 2nd Norwegian moose
14/06/2016 - Norway reports a third case
Saturday, July 16, 2016
Chronic wasting Disease in Deer (CWD or Spongiform Encephalopathy) The British Deer Society 07/04/2016
Red Deer Ataxia or Chronic Wasting Disease CWD TSE PRION?
could this have been cwd in the UK back in 1970’S ???
SEE FULL TEXT ;
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.
***Recently, we have been using PMCA to study the role of environmental prion contamination on the horizontal spreading of TSEs. These experiments have focused on the study of the interaction of prions with plants and environmentally relevant surfaces. Our results show that plants (both leaves and roots) bind tightly to prions present in brain extracts and excreta (urine and feces) and retain even small quantities of PrPSc for long periods of time. Strikingly, ingestion of prioncontaminated leaves and roots produced disease with a 100% attack rate and an incubation period not substantially longer than feeding animals directly with scrapie brain homogenate. Furthermore, plants can uptake prions from contaminated soil and transport them to different parts of the plant tissue (stem and leaves). Similarly, prions bind tightly to a variety of environmentally relevant surfaces, including stones, wood, metals, plastic, glass, cement, etc. Prion contaminated surfaces efficiently transmit prion disease when these materials were directly injected into the brain of animals and strikingly when the contaminated surfaces were just placed in the animal cage. These findings demonstrate that environmental materials can efficiently bind infectious prions and act as carriers of infectivity, suggesting that they may play an important role in the horizontal transmission of the disease.
========================
Since its invention 13 years ago, PMCA has helped to answer fundamental questions of prion propagation and has broad applications in research areas including the food industry, blood bank safety and human and veterinary disease diagnosis.
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
Wednesday, December 16, 2015
*** Objects in contact with classical scrapie sheep act as a reservoir for scrapie transmission ***
*** Infectious agent of sheep scrapie may persist in the environment for at least 16 years ***
Gudmundur Georgsson1, Sigurdur Sigurdarson2 and Paul Brown3
with CWD TSE Prions, I am not sure there is any absolute yet, other than what we know with transmission studies, and we know tse prion kill, and tse prion are bad. science shows to date, that indeed soil, dirt, some better than others, can act as a carrier. same with objects, farm furniture. take it with how ever many grains of salt you wish, or not. if load factor plays a role in the end formula, then everything should be on the table, in my opinion...tss
Oral Transmissibility of Prion Disease Is Enhanced by Binding to Soil Particles
Author Summary
Transmissible spongiform encephalopathies (TSEs) are a group of incurable neurological diseases likely caused by a misfolded form of the prion protein. TSEs include scrapie in sheep, bovine spongiform encephalopathy (‘‘mad cow’’ disease) in cattle, chronic wasting disease in deer and elk, and Creutzfeldt-Jakob disease in humans. Scrapie and chronic wasting disease are unique among TSEs because they can be transmitted between animals, and the disease agents appear to persist in environments previously inhabited by infected animals. Soil has been hypothesized to act as a reservoir of infectivity and to bind the infectious agent. In the current study, we orally dosed experimental animals with a common clay mineral, montmorillonite, or whole soils laden with infectious prions, and compared the transmissibility to unbound agent. We found that prions bound to montmorillonite and whole soils remained orally infectious, and, in most cases, increased the oral transmission of disease compared to the unbound agent. The results presented in this study suggest that soil may contribute to environmental spread of TSEs by increasing the transmissibility of small amounts of infectious agent in the environment.
tse prion soil
Wednesday, December 16, 2015
Objects in contact with classical scrapie sheep act as a reservoir for scrapie transmission
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.
>>>Particle-associated PrPTSE molecules may migrate from locations of deposition via transport processes affecting soil particles, including entrainment in and movement with air and overland flow. <<<
Fate of Prions in Soil: A Review
Christen B. Smith, Clarissa J. Booth, and Joel A. Pedersen*
Several reports have shown that prions can persist in soil for several years. Significant interest remains in developing methods that could be applied to degrade PrPTSE in naturally contaminated soils. Preliminary research suggests that serine proteases and the microbial consortia in stimulated soils and compost may partially degrade PrPTSE. Transition metal oxides in soil (viz. manganese oxide) may also mediate prion inactivation. Overall, the effect of prion attachment to soil particles on its persistence in the environment is not well understood, and additional study is needed to determine its implications on the environmental transmission of scrapie and CWD.
P.161: Prion soil binding may explain efficient horizontal CWD transmission
Conclusion. Silty clay loam exhibits highly efficient prion binding, inferring a durable environmental reservoir, and an efficient mechanism for indirect horizontal CWD transmission.
>>>Another alternative would be an absolute prohibition on the movement of deer within the state for any purpose. While this alternative would significantly reduce the potential spread of CWD, it would also have the simultaneous effect of preventing landowners and land managers from implementing popular management strategies involving the movement of deer, and would deprive deer breeders of the ability to engage in the business of buying and selling breeder deer. Therefore, this alternative was rejected because the department determined that it placed an avoidable burden on the regulated community.<<<
Wednesday, December 16, 2015
Objects in contact with classical scrapie sheep act as a reservoir for scrapie transmission
Timm Konold1*, Stephen A. C. Hawkins2, Lisa C. Thurston3, Ben C. Maddison4, Kevin C. Gough5, Anthony Duarte1 and Hugh A. Simmons1
1 Animal Sciences Unit, Animal and Plant Health Agency Weybridge, Addlestone, UK, 2 Pathology Department, Animal and Plant Health Agency Weybridge, Addlestone, UK, 3 Surveillance and Laboratory Services, Animal and Plant Health Agency Penrith, Penrith, UK, 4 ADAS UK, School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington, UK, 5 School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington, UK
Classical scrapie is an environmentally transmissible prion disease of sheep and goats. Prions can persist and remain potentially infectious in the environment for many years and thus pose a risk of infecting animals after re-stocking. In vitro studies using serial protein misfolding cyclic amplification (sPMCA) have suggested that objects on a scrapie affected sheep farm could contribute to disease transmission. This in vivo study aimed to determine the role of field furniture (water troughs, feeding troughs, fencing, and other objects that sheep may rub against) used by a scrapie-infected sheep flock as a vector for disease transmission to scrapie-free lambs with the prion protein genotype VRQ/VRQ, which is associated with high susceptibility to classical scrapie. When the field furniture was placed in clean accommodation, sheep became infected when exposed to either a water trough (four out of five) or to objects used for rubbing (four out of seven). This field furniture had been used by the scrapie-infected flock 8 weeks earlier and had previously been shown to harbor scrapie prions by sPMCA. Sheep also became infected (20 out of 23) through exposure to contaminated field furniture placed within pasture not used by scrapie-infected sheep for 40 months, even though swabs from this furniture tested negative by PMCA. This infection rate decreased (1 out of 12) on the same paddock after replacement with clean field furniture. Twelve grazing sheep exposed to field furniture not in contact with scrapie-infected sheep for 18 months remained scrapie free. The findings of this study highlight the role of field furniture used by scrapie-infected sheep to act as a reservoir for disease re-introduction although infectivity declines considerably if the field furniture has not been in contact with scrapie-infected sheep for several months. PMCA may not be as sensitive as VRQ/VRQ sheep to test for environmental contamination.
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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
Wednesday, December 16, 2015
*** Objects in contact with classical scrapie sheep act as a reservoir for scrapie transmission ***
*** Infectious agent of sheep scrapie may persist in the environment for at least 16 years ***
Gudmundur Georgsson1, Sigurdur Sigurdarson2 and Paul Brown3
MONDAY, JUNE 12, 2017
Rethinking Major grain organizations opposition to CFIA's control zone approach to Chronic Wasting CWD TSE Prion Mad Deer Type Disease 2017?
WEDNESDAY, MAY 17, 2017
*** Chronic Wasting Disease CWD TSE Prion aka Mad Deer Disease and the Real Estate Market Land Values ***
Tuesday, April 12, 2016
The first detection of Chronic Wasting Disease (CWD) in Europe free-ranging reindeer from the Nordfjella population in South-Norway.
Saturday, April 9, 2016
The Norwegian Veterinary Institute (NVI, 2016) has reported a case of prion disease Cervid Spongiform Encephalopathy detected in free ranging wild reindeer (Rangifer tarandus tarandus)
Department for Environment, Food and Rural Affairs
Wednesday, September 28, 2016
Norway sides with OIE, decides to expose millions of consumers to the ATYPICAL BSE SRM TSE Prion aka mad cow type disease
Thursday, January 29, 2015
Atypical H-TYPE BSE Case Confirmed in Norway
MONDAY, JULY 17, 2017
National Scrapie Eradication Program May 2017 Monthly Report Fiscal Year 2017
TUESDAY, JULY 18, 2017
MINK FARMING USA TRANSMISSIBLE MINK ENCEPHALOPATHY TSE PRION DISEASE SURVEILLANCE AND TESTING
THURSDAY, JULY 13, 2017
EFSA BSE Sixty cases of mad cow disease since 2001 breached feed ban likely the cause
Scientists investigate origin of isolated BSE cases
TUESDAY, JULY 18, 2017
USDA announces Alabama case of Bovine Spongiform Encephalopathy Alabama
THURSDAY, JULY 20, 2017
USDA OIE Alabama Atypical L-type BASE Bovine Spongiform Encephalopathy BSE animal feeds for ruminants rule, 21 CFR 589.200
SUNDAY, JULY 23, 2017
atypical L-type BASE Bovine Amyloidotic Spongiform Encephalopathy BSE TSE PRION
SUNDAY, JULY 23, 2017
Experimental Infection of Cattle With a Novel Prion Derived From Atypical H-Type Bovine Spongiform Encephalopathy
SCRAPIE WS-01: Prion diseases in animals and zoonotic potential 2016
Prion. 10:S15-S21. 2016 ISSN: 1933-6896 printl 1933-690X online
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.
-------- Original Message --------
Subject: re-BSE prions propagate as either variant CJD-like or sporadic CJD
Date: Thu, 28 Nov 2002 10:23:43 -0000 From: "Asante, Emmanuel A" e.asante@ic.ac.uk
To: "'flounder@wt.net'" flounder@wt.net
Dear Terry,
I have been asked by Professor Collinge to respond to your request. I am a Senior Scientist in the MRC Prion Unit and the lead author on the paper. I have attached a pdf copy of the paper for your attention.
Thank you for your interest in the paper. In respect of your first question, the simple answer is, ***yes.
As you will find in the paper, we have managed to associate the alternate phenotype to type 2 PrPSc, the commonest sporadic CJD.
It is too early to be able to claim any further sub-classification in respect of Heidenhain variant CJD or Vicky Rimmer's version.
It will take further studies, which are on-going, to establish if there are sub-types to our initial finding which we are now reporting.
The main point of the paper is that, as well as leading to the expected new variant CJD phenotype, BSE transmission to the 129-methionine genotype can lead to an alternate phenotype which is indistinguishable from type 2 PrPSc.
I hope reading the paper will enlighten you more on the subject. If I can be of any further assistance please to not hesitate to ask.
Best wishes. Emmanuel Asante <>
____________________________________
Dr. Emmanuel A Asante MRC Prion Unit & Neurogenetics Dept. Imperial College School of Medicine (St. Mary's) Norfolk Place, LONDON W2 1PG Tel: +44 (0)20 7594 3794 Fax: +44 (0)20 7706 3272 email: e.asante@ic.ac.uk (until 9/12/02) New e-mail: e.asante@prion.ucl.ac.uk (active from now)
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end...TSS
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***********OCTOBER 2015*************
*** PRION 2015 ORAL AND POSTER CONGRESSIONAL ABSTRACTS ***
THANK YOU PRION 2015 TAYLOR & FRANCIS, Professor Chernoff, and Professor Aguzzi et al, for making these PRION 2015 Congressional Poster and Oral Abstracts available freely to the public. ...Terry S. Singeltary Sr.
P.108: Successful oral challenge of adult cattle with classical BSE
Sandor Dudas1,*, Kristina Santiago-Mateo1, Tammy Pickles1, Catherine Graham2, and Stefanie Czub1 1Canadian Food Inspection Agency; NCAD Lethbridge; Lethbridge, Alberta, Canada; 2Nova Scotia Department of Agriculture; Pathology Laboratory; Truro, Nova Scotia, Canada
Classical Bovine spongiform encephalopathy (C-type BSE) is a feed- and food-borne fatal neurological disease which can be orally transmitted to cattle and humans. Due to the presence of contaminated milk replacer, it is generally assumed that cattle become infected early in life as calves and then succumb to disease as adults. Here we challenged three 14 months old cattle per-orally with 100 grams of C-type BSE brain to investigate age-related susceptibility or resistance. During incubation, the animals were sampled monthly for blood and feces and subjected to standardized testing to identify changes related to neurological disease. At 53 months post exposure, progressive signs of central nervous system disease were observed in these 3 animals, and they were euthanized. Two of the C-BSE animals tested strongly positive using standard BSE rapid tests, however in 1 C-type challenged animal, Prion 2015 Poster Abstracts S67 PrPsc was not detected using rapid tests for BSE. Subsequent testing resulted in the detection of pathologic lesion in unusual brain location and PrPsc detection by PMCA only.
***Our study demonstrates susceptibility of adult cattle to oral transmission of classical BSE.
We are further examining explanations for the unusual disease presentation in the third challenged animal.
***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.
P.86: Estimating the risk of transmission of BSE and scrapie to ruminants and humans by protein misfolding cyclic amplification
Morikazu Imamura, Naoko Tabeta, Yoshifumi Iwamaru, and Yuichi Murayama National Institute of Animal Health; Tsukuba, Japan
To assess the risk of the transmission of ruminant prions to ruminants and humans at the molecular level, we investigated the ability of abnormal prion protein (PrPSc) of typical and atypical BSEs (L-type and H-type) and typical scrapie to convert normal prion protein (PrPC) from bovine, ovine, and human to proteinase K-resistant PrPSc-like form (PrPres) using serial protein misfolding cyclic amplifi- cation (PMCA).
Six rounds of serial PMCA was performed using 10% brain homogenates from transgenic mice expressing bovine, ovine or human PrPC in combination with PrPSc seed from typical and atypical BSE- or typical scrapie-infected brain homogenates from native host species. In the conventional PMCA, the conversion of PrPC to PrPres was observed only when the species of PrPC source and PrPSc seed matched. However, in the PMCA with supplements (digitonin, synthetic polyA and heparin), both bovine and ovine PrPC were converted by PrPSc from all tested prion strains. On the other hand, human PrPC was converted by PrPSc from typical and H-type BSE in this PMCA condition.
Although these results were not compatible with the previous reports describing the lack of transmissibility of H-type BSE to ovine and human transgenic mice, 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.
P.170: Potential detection of oral transmission of H type atypical BSE in cattle using in vitro conversion
***P.170: Potential detection of oral transmission of H type atypical BSE in cattle using in vitro conversion
Sandor Dudas, John G Gray, Renee Clark, and Stefanie Czub Canadian Food Inspection Agency; Lethbridge, AB Canada
Keywords: Atypical BSE, oral transmission, RT-QuIC
The detection of bovine spongiform encephalopathy (BSE) has had a significant negative impact on the cattle industry worldwide. In response, governments took actions to prevent transmission and additional threats to animal health and food safety. While these measures seem to be effective for controlling classical BSE, the more recently discovered atypical BSE has presented a new challenge. To generate data for risk assessment and control measures, we have challenged cattle orally with atypical BSE to determine transmissibility and mis-folded prion (PrPSc) tissue distribution. Upon presentation of clinical symptoms, animals were euthanized and tested for characteristic histopathological changes as well as PrPSc deposition.
The H-type challenged animal displayed vacuolation exclusively in rostral brain areas but the L-type challenged animal showed no evidence thereof. To our surprise, neither of the animals euthanized, which were displaying clinical signs indicative of BSE, showed conclusive mis-folded prion accumulation in the brain or gut using standard molecular or immunohistochemical assays. To confirm presence or absence of prion infectivity, we employed an optimized real-time quaking induced conversion (RT-QuIC) assay developed at the Rocky Mountain Laboratory, Hamilton, USA.
Detection of PrPSc was unsuccessful for brain samples tests from the orally inoculated L type animal using the RT-QuIC. It is possible that these negative results were related to the tissue sampling locations or that type specific optimization is needed to detect PrPSc in this animal. We were however able to consistently detect the presence of mis-folded prions in the brain of the H-type inoculated animal. Considering the negative and inconclusive results with other PrPSc detection methods, positive results using the optimized RT-QuIC suggests the method is extremely sensitive for H-type BSE detection. This may be evidence of the first successful oral transmission of H type atypical BSE in cattle and additional investigation of samples from these animals are ongoing.
Discussion: The C, L and H type BSE cases in Canada exhibit molecular characteristics similar to those described for classical and atypical BSE cases from Europe and Japan.
*** This supports the theory that the importation of BSE contaminated feedstuff is the source of C-type BSE in Canada.
*** It also suggests a similar cause or source for atypical BSE in these countries. ***
P.9.21
Molecular characterization of BSE in Canada
Jianmin Yang 1 , Sandor Dudas 2 , Catherine Graham 2 , Markus Czub 3 , Tim McAllister 1 , Stefanie Czub 1 1 Agriculture and Agri-Food Canada Research Centre, Canada; 2 National and OIE BSE Reference Laboratory, Canada; 3 University of Calgary, Canada
Background: Three BSE types (classical and two atypical) have been identified on the basis of molecular characteristics of the misfolded protein associated with the disease. To date, each of these three types have been detected in Canadian cattle. Objectives: This study was conducted to further characterize the 16 Canadian BSE cases based on the biochemical properties of there associated PrPres.
Methods: Immuno-reactivity, molecular weight, glycoform profiles and relative proteinase K sensitivity of the PrPres from each of the 16 confirmed Canadian BSE cases was determined using modified Western blot analysis.
Results: Fourteen of the 16 Canadian BSE cases were C type, 1 was H type and 1 was L type. The Canadian H and L-type BSE cases exhibited size shifts and changes in glycosylation similar to other atypical BSE cases. PK digestion under mild and stringent conditions revealed a reduced protease resistance of the atypical cases compared to the C-type cases. N terminal-specific antibodies bound to PrPres from H type but not from C or L type. The C-terminal-specific antibodies resulted in a shift in the glycoform profile and detected a fourth band in the Canadian H-type BSE.
Discussion: The C, L and H type BSE cases in Canada exhibit molecular characteristics similar to those described for classical and atypical BSE cases from Europe and Japan. This supports the theory that the importation of BSE contaminated feedstuff is the source of C-type BSE in Canada. It also suggests a similar cause or source for atypical BSE in these countries.
see page 176 of 201 pages...tss
*** Singeltary reply ; Molecular, Biochemical and Genetic Characteristics of BSE in Canada Singeltary reply;
***however in 1 C-type challenged animal, Prion 2015 Poster Abstracts S67 PrPsc was not detected using rapid tests for BSE.
***Subsequent testing resulted in the detection of pathologic lesion in unusual brain location and PrPsc detection by PMCA only.
IBNC Tauopathy or TSE Prion disease, it appears, no one is sure
Posted by flounder on 03 Jul 2015 at 16:53 GMT
2014
***Moreover, L-BSE has been transmitted more easily to transgenic mice overexpressing a human PrP [13,14] or to primates [15,16] than C-BSE.
***It has been suggested that some sporadic CJD subtypes in humans may result from an exposure to the L-BSE agent.
*** Lending support to this hypothesis, pathological and biochemical similarities have been observed between L-BSE and an sCJD subtype (MV genotype at codon 129 of PRNP) [17], and between L-BSE infected non-human primate and another sCJD subtype (MM genotype) [15].
snip...
Saturday, April 23, 2016
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
Juan Maria Torres a, Olivier Andreoletti b, Juan-Carlos Espinosa a. Vincent Beringue c. Patricia Aguilar a,
Natalia Fernandez-Borges a. and Alba Marin-Moreno a
"Centro de Investigacion en Sanidad Animal ( CISA-INIA ). Valdeolmos, Madrid. Spain; b UMR INRA -ENVT 1225 Interactions Holes Agents Pathogenes. ENVT. Toulouse. France: "UR892. Virologie lmmunologie MolécuIaires, Jouy-en-Josas. France
Dietary exposure to bovine spongiform encephalopathy (BSE) contaminated bovine tissues is considered as the origin of variant Creutzfeldt Jakob (vCJD) disease in human. To date, BSE agent is the only recognized zoonotic prion. Despite the variety of Transmissible Spongiform Encephalopathy (TSE) agents that have been circulating for centuries in farmed ruminants there is no apparent epidemiological link between exposure to ruminant products and the occurrence of other form of TSE in human like sporadic Creutzfeldt Jakob Disease (sCJD). However, the zoonotic potential of the diversity of circulating TSE agents has never been systematically assessed. The major issue in experimental assessment of TSEs zoonotic potential lies in the modeling of the ‘species barrier‘, the biological phenomenon that limits TSE agents’ propagation from a species to another. In the last decade, mice genetically engineered to express normal forms of the human prion protein has proved essential in studying human prions pathogenesis and modeling the capacity of TSEs to cross the human species barrier.
To assess the zoonotic potential of prions circulating in farmed ruminants, we study their transmission ability in transgenic mice expressing human PrPC (HuPrP-Tg). Two lines of mice expressing different forms of the human PrPC (129Met or 129Val) are used to determine the role of the Met129Val dimorphism in susceptibility/resistance to the different agents.
These transmission experiments confirm the ability of BSE prions to propagate in 129M- HuPrP-Tg mice and demonstrate that Met129 homozygotes may be susceptible to BSE in sheep or goat to a greater degree than the BSE agent in cattle and that these agents can convey molecular properties and neuropathological indistinguishable from vCJD. However homozygous 129V mice are resistant to all tested BSE derived prions independently of the originating species suggesting a higher transmission barrier for 129V-PrP variant.
Transmission data also revealed that several scrapie prions propagate in HuPrP-Tg mice with efficiency comparable to that of cattle BSE. While the efficiency of transmission at primary passage was low, subsequent passages resulted in a highly virulent prion disease in both Met129 and Val129 mice. Transmission of the different scrapie isolates in these mice leads to the emergence of prion strain phenotypes that showed similar characteristics to those displayed by MM1 or VV2 sCJD prion. These results demonstrate that scrapie prions have a zoonotic potential and raise new questions about the possible link between animal and human prions.
SPONTANEOUS ATYPICAL BOVINE SPONGIFORM ENCEPHALOPATHY
***Moreover, sporadic disease has never been observed in breeding colonies or primate research laboratories, most notably among hundreds of animals over several decades of study at the National Institutes of Health25, and in nearly twenty older animals continuously housed in our own facility.***
why do we not want to do TSE transmission studies on chimpanzees $
5. A positive result from a chimpanzee challenged severly would likely create alarm in some circles even if the result could not be interpreted for man. I have a view that all these agents could be transmitted provided a large enough dose by appropriate routes was given and the animals kept long enough. Until the mechanisms of the species barrier are more clearly understood it might be best to retain that hypothesis.
snip...
R. BRADLEY
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.
2001 FDA CJD TSE Prion Singeltary Submission
*** U.S.A. 50 STATE BSE MAD COW CONFERENCE CALL Jan. 9, 2001
VPSPr
Variably protease-sensitive prionopathy (VPSPr), a recently identified and seemingly sporadic human prion disease, is distinct from Creutzfeldt-Jakob disease (CJD) but shares features of Gerstmann-Sträussler-Scheinker disease (GSS). However, contrary to exclusively inherited GSS, no prion protein (PrP) gene variations have been detected in VPSPr, suggesting that VPSPr might be the long-sought sporadic form of GSS.
snip...
In conclusion, we propose that VPSPr is transmissible and, therefore, is an authentic prion disease. However, transmissibility cannot be sustained through serial passages presumably because human PrPC (or the mouse brain environment) cannot efficiently convert and propagate the VPSPr PrPSc species. If this is the case, uncovering the properties of human PrP that are required to replicate more efficiently the prion strains associated with VPSPr may help clarify the PrPSc mode of formation in this intriguing disease.
Friday, January 10, 2014
vpspr, sgss, sffi, TSE, an iatrogenic by-product of gss, ffi, familial type prion disease, what it ???
THURSDAY, JULY 13, 2017
TEXAS CREUTZFELDT JAKOB DISEASE CJD TSE PRION
National Prion Center could lose all funding just as concern about CWD jumping to humans rises
SATURDAY, JULY 15, 2017
*** National Prion Center could lose all funding just as concern about CWD jumping to humans rises
SATURDAY, JULY 22, 2017
Why the U.S. Needs to Continue Prion Disease Surveillance, instead of reducing funding to zero
SPONTANEOUS ATYPICAL BOVINE SPONGIFORM ENCEPHALOPATHY
***Moreover, sporadic disease has never been observed in breeding colonies or primate research laboratories, most notably among hundreds of animals over several decades of study at the National Institutes of Health25, and in nearly twenty older animals continuously housed in our own facility.***
National Prion Center could lose all funding just as concern about CWD jumping to humans rises
SATURDAY, JULY 15, 2017
*** National Prion Center could lose all funding just as concern about CWD jumping to humans rises
National Prion Center could lose all funding just as concern about CWD jumping to humans rises
SATURDAY, JULY 15, 2017
*** National Prion Center could lose all funding just as concern about CWD jumping to humans rises
SATURDAY, JULY 22, 2017
Why the U.S. Needs to Continue Prion Disease Surveillance, instead of reducing funding to zero
SPONTANEOUS ATYPICAL BOVINE SPONGIFORM ENCEPHALOPATHY
***Moreover, sporadic disease has never been observed in breeding colonies or primate research laboratories, most notably among hundreds of animals over several decades of study at the National Institutes of Health25, and in nearly twenty older animals continuously housed in our own facility.***
CWD state by state
WEDNESDAY, JULY 26, 2017
Chronic wasting disease continues to spread Disease of cervids causing local population declines
TUESDAY, JULY 18, 2017
USDA announces Alabama case of Bovine Spongiform Encephalopathy Alabama
THURSDAY, JULY 20, 2017
USDA OIE Alabama Atypical L-type BASE Bovine Spongiform Encephalopathy BSE animal feeds for ruminants rule, 21 CFR 589.200
SUNDAY, JULY 30, 2017
Do we need to explain the occurrence of atypical scrapie?
TUESDAY, JULY 18, 2017
MINK FARMING USA TRANSMISSIBLE MINK ENCEPHALOPATHY TSE PRION DISEASE SURVEILLANCE AND TESTING
WEDNESDAY, APRIL 05, 2017
Disease-associated prion protein detected in lymphoid tissues from pigs challenged with the agent of chronic wasting disease
TUESDAY, APRIL 18, 2017
*** EXTREME USA FDA PART 589 TSE PRION FEED LOOP HOLE STILL EXIST, AND PRICE OF POKER GOES UP ***
WEDNESDAY, JULY 26, 2017
APHIS USDA Emerging Animal Disease Preparedness and Response Plan July 2017
Terry S. Singeltary Sr.
posted by Terry S. Singeltary Sr. at
5:19 PM
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