Scientific opinion on chronic wasting disease (II) EFSA Panel on Biological Hazards (BIOHAZ)
Subject: Scientific opinion on chronic wasting disease (II) EFSA Panel on Biological Hazards (BIOHAZ)ADOPTED: 6 December 2017 doi: 10.2903/j.efsa.2018.5132Scientific opinion on chronic wasting disease (II)EFSA Panel on Biological Hazards (BIOHAZ),Antonia Ricci, Ana Allende, Declan Bolton, Marianne Chemaly, Robert Davies,Pablo Salvador Ferna ndez Esca mez, Rosina Girone s, Lieve Herman, Kostas Koutsoumanis, Roland Lindqvist, Birgit Nørrung, Lucy Robertson, Giuseppe Ru, Moez Sanaa, Panagiotis Skandamis, Emma Snary, Niko Speybroeck, Benno Ter Kuile, John Threlfall, Helene Wahlstro€m, Sylvie Benestad, Dolores Gavier-Widen, Michael W Miller, Glenn C Telling, Morten Tryland, Francesca Latronico, Angel Ortiz-Pelaez, Pietro Stella and Marion SimmonsAbstractThe European Commission asked EFSA for a scientific opinion on chronic wasting disease in two parts. Part one, on surveillance, animal health risk-based measures and public health risks, was published in January 2017. This opinion (part two) addresses the remaining Terms of Reference, namely, ‘are the conclusions and recommendations in the EFSA opinion of June 2004 on diagnostic methods for chronic wasting disease still valid? If not, an update should be provided’, and ‘update the conclusions of the 2010 EFSA opinion on the results of the European Union survey on chronic wasting disease in cervids, as regards its occurrence in the cervid population in the European Union’. Data on the performance of authorised rapid tests in North America are not comprehensive, and are more limited than those available for the tests approved for statutory transmissible spongiform encephalopathies surveillance applications in cattle and sheep. There are no data directly comparing available rapid test performances in cervids. The experience in Norway shows that the Bio-Rad TeSeETM SAP test, immunohistochemistry and western blotting have detected reindeer, moose and red deer cases. It was shown that testing both brainstem and lymphoid tissue from each animal increases the surveillance sensitivity. Shortcomings in the previous EU survey limited the reliability of inferences that could be made about the potential disease occurrence in Europe. Subsequently, testing activity in Europe was low, until the detection of the disease in Norway, triggering substantial testing efforts in that country. Available data neither support nor refute the conclusion that chronic wasting disease does not occur widely in the EU and do not preclude the possibility that the disease was present in Europe before the survey was conducted. It appears plausible that chronic wasting disease could have become established in Norway more than a decade ago.© 2018 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.Keywords: chronic, wasting, cervids, diagnostic, occurrenceRequestor: European Commission Question number: EFSA-Q-2016-00411 Correspondence: biohaz@efsa.europa.euSummaryIn 2016, the European Food Safety Authority (EFSA) was asked by the European Commission to deliver a scientific opinion on three Terms of Reference (ToRs): (1) surveillance, (2) public health and (3) (animal health risk-based measures) by 31 December 2016. On 18 January 2017, EFSA published a scientific opinion on chronic wasting disease (CWD) in cervids addressing these three ToRs (EFSA BIOHAZ Panel, 2017a). Within the same mandate, EFSA was asked to deliver by 31 December 2017 a scientific opinion on the following ToR: (4) are the conclusions and recommendations in the EFSA opinion of June 2004 on diagnostic methods for CWD still valid? If not, an update should be provided, and (5) update the conclusions of the 2010 EFSA opinion on the results of the European Union (EU) survey on CWD in cervids, as regards the occurrence of CWD in the cervid population in the EU.No formal validation of test performance equivalent to the existing EU requirements for tests used for statutory surveillance in cattle and sheep has been undertaken for cervid material. A qualitative evaluation of the suitability of the Bio-Rad and the IDEXX rapid tests (RT) commercially available for the diagnosis of CWD was carried out by means of literature review (both an ad hoc literature review on the diagnosis of CWD and the references retrieved by the search conducted for the 2017 Opinion (EFSA BIOHAZ Panel, 2017a)), the data provided by the manufacturers, and the knowledge and expertise of the Working Group (WG) members.A review of the available approaches to the diagnosis of CWD including the considerations underpinning the selection of animals, tissues and diagnostic tests has been conducted, as well as a review of the different diagnostic methods applied for the detection of CWD, both in the context of large-scale surveillance and for research purposes. Screening tests and confirmatory diagnostic methods have been reviewed along with methods for classification of isolates based on data from confirmatory testing, bioassay in potential natural host species and bioassay in rodent models. Requirements for the validation of new diagnostic tests, in particular, the steps and different pathways as defined by the International Organization of Animal Health (OIE) for validation of tests for wild populations, were considered. A review of all the validation exercises of RT for the detection of bovine spongiform encephalopathy (BSE) and for the diagnosis of transmissible spongiform encephalopathies (TSE) in small ruminants conducted in the EU has been included for comparison with the data current available for the rapid tests presently used for the detection of CWD in North America.Sensitive amplification methods, such as protein misfolding cyclic amplification (PMCA) and real- time quaking-induced conversion (rtQuiC) that are currently under development for in vivo screening, or for the detection of environmental contamination, are also considered, but they are not yet at a point in their development where they could be applied in a statutory surveillance context.To demonstrate how the potential for patchy CWD distribution could complicate surveillance in a heterogeneous geographic area the size of Europe, historical and contemporary maps of CWD distribution in the 28 contiguous US states east of the Mississippi River, spanning ~ 2.5 M km2, were used. This area approximates the EU (28 Member States (MS): > 4.4 M km2) with respect to several ecological, epidemiological and jurisdictional features relevant to CWD surveillance in the context of ToR 5.Data on surveillance in Europe in 2015, 2016 and 2017 were extracted from annual reports submitted by the MS, and from the background information provided by the European Commission, and included in the mandate and the European Commission database. Surveillance data from Norway for the period 1 January 2017–27 November 2017 have been provided by the Norwegian Veterinary Institute, upon request. These data were used together with historical surveillance data from five Colorado mule deer herds collected over 15–21 years to provide a temporal reference of the estimated prevalence in new incursions of CWD and potential time lags in ‘epidemic’ emergence. Data from North America were used to generate a composite epidemic curve, and data from a published model were graphed for comparison with the observed data. The point estimate of comparable survey data from Norwegian reindeer (Nordfjella 1 region) was also calculated.The experience in Norway so far shows that the Bio-Rad RT (TeSeETM SAP) has detected cases of CWD in reindeer, moose and red deer. It has also been shown that antibodies raised against the core or C-terminal parts of the prion protein used for immunohistochemistry (IHC) and western blot (WB) were able to detect these cases.Developments in immunoblotting techniques have resulted in the ability to discriminate experimental BSE from CWD in red deer. However, there is only limited information on the biological and molecular characteristics that define different strains in the North American cervid population against which the EU isolates could be compared and classified.The conclusions (1, 2, 3, 4) and recommendations (3, 5, 6, 7) of the 2004 EFSA opinion on diagnostic methods for CWD remain valid. The available formal data on the performance of authorised RT for the detection of CWD in cervids in North America are not comprehensive and are much more limited than those available for the detection of BSE in cattle and scrapie in sheep. The lack of sufficient positive reference samples Europe, and a current lack of information on the strain(s) that might be circulating, make the estimation of the diagnostic sensitivity (DSe) of any test unfeasible for cervid samples, and preclude the development of alternative tests for use in European TSE surveillance in cervids. No direct comparison of test performance (i.e. parallel testing on the same panel of samples) can be made from the data available so there is no possibility to identify any differences between the two RT available on the market.The generation of positive control material for European CWD strain/s, as recommended in both the 2004 and 2010 EFSA opinions (EFSA, 2004a,b; EFSA BIOHAZ Panel, 2010), for example, by experimental inoculation of a range of cervid species would be useful but is very difficult to perform, and would raise a number of practical and welfare issues. It would require the maintenance of experimentally infected individuals from non-domesticated species in high biosafety facilities for a long period of time. In the absence of the specific pathogenesis data that such studies would provide and in the light of the results from the Norwegian surveillance, both brainstem and lymphoid tissue should be tested from each animal to improve sensitivity possible from collected material. The added sensitivity conferred by the testing of lymphoid tissues in addition to the brainstem is further corroborated by the experience from the testing conducted in Norway; three out of the eight positive reindeer were positive on lymphoid tissue only and five were positive in both brainstem and lymphoid tissue. Similarly, the Norwegian experience indicates that there was no detectable lymphoid involvement in the moose and red deer cases.The tissue distribution of infectivity in some CWD-infected cervids is now known to extend beyond the central nervous system and lymphoid tissues. While the removal of these specific tissues from the food chain, as recommended in the 2004 Opinion, would reduce human dietary exposure to infectivity, exclusion from the food chain of the whole carcass of any infected animal would be required to eliminate human dietary exposure.The conclusions (1, 2, 4, 5, 6) and all recommendations (1, 2, 3, 4) of the 2010 EFSA opinion remain valid. Shortcomings in the 2006–2010 EU CWD survey design and subsequent implementation limited the reliability of inferences that could be made about the potential occurrence of CWD in Europe. Despite the lack of substantial surveillance in the EU since that time, cases of CWD have now been detected in wild Norwegian reindeer, moose and red deer, confirming the long-held suspicion that at least some European cervid species are susceptible. Since the implementation of the 2006–2010 EU survey, testing activity has been low in Europe until the detection of CWD in Norway triggered a substantial testing effort in this country in 2016 and 2017. The surveillance programme proposed in the 2017 EFSA opinion supersedes the specifications of the EU-wide survey that was implemented following the recommendations of the 2004 EFSA opinion.Current available data do not preclude the possibility that CWD was present in Norway and perhaps elsewhere in Europe before the 2006–2010 EU CWD survey was conducted, whether in epidemic form or not. Comparing the point estimates of CWD prevalence among ‘adult’ (> 1 year old) reindeer harvested in Nordfjella 1 in 2016 (0.97%, 95% C.I.: 0.2–2.8%) and for the period 1 January–27 November 2017 (0.68%, 95% CI: 0.22–1.6%) to the epidemic curve for mule deer in investigated herds in the US, it appears plausible that CWD could have become established in Norway more than a decade ago.Adhering to contemporary surveillance recommendations (EFSA BIOHAZ Panel, 2017a), especially with respect to focusing sampling on high-risk individuals and developing a biologically meaningful spatial sampling framework relevant to the populations being monitored, with the aim of achieving set target sample sizes at the primary sampling unit level, should improve the reliability and value of data arising from renewed CWD surveillance efforts by some MS in coming years. The finding of the first case of CWD in red deer in Norway means that the surveillance scheme as in Reg. 999/2001, as amended, does not cover geographically all the MS in which red deer are present.Further recommendations have been made, among them, the incorporation of sampling and testing for CWD into any wildlife health surveillance programmes, and the increase of awareness and dissemination of information about CWD in appropriate forums in the EU in order to improve the reporting of suspect cases. In addition, it is recommended to use only trained personnel for sample collection, and to avoid any test or detection method that uses antibodies for which the epitope is known to be polymorphic in cervids, unless successful binding in positive animals with those polymorphisms can be demonstrated. Residual samples, including relevant metadata, should be retained from all positive animals, and from as many tissues as possible, for isolate classification, future test evaluation, epidemiology or research purposes. Complementary studies should be conducted to identify any relevant differences influencing the epidemiology of the disease and to investigate the presence and frequency of potentially resistant alleles in the European cervid population. Finally, it is recommended to keep the performance of all currently applied tests, including those still being developed, under review and revise and update statutory testing protocols as new data become available.Snip...5. RecommendationsTo incorporate sampling and testing for CWD into any wildlife surveillance programmes. Such programmes would need to take into account the knowledge gained in the CWD field and apply it to the surveillance strategies as suggested by OIE. In particular, surveillance should focus on clinical suspects and other high-risk animals.To increase awareness and to disseminate information about CWD in appropriate forums in the EU in order to improve the reporting of suspect cases.NORWAY CHRONIC WASTING DISEASE CWD TSE PRIONTUESDAY, DECEMBER 05, 2017Norway 30,000 deer animals have so far been tested for Skrantesyke chronic wasting disease CWD TSE PRION DISEASETHURSDAY, NOVEMBER 30, 2017Norway Animal welfare surveillance at Nordfjella Skrantesjuke CWD TSE Prion UpdateWEDNESDAY, NOVEMBER 29, 2017Norway another case of Skrantesjuke CWD TSE Prion Adult Reindeer pitcher field in Nordfjella (preliminary testing) 13th case if confirmedFRIDAY, NOVEMBER 24, 2017Norwegian Food Safety Authority makes changes to measures to limit the spread of disease Skrantesjuke (CWD) in deer wildlifeSATURDAY, NOVEMBER 18, 2017Norway detects more Chronic Wasting Disease CWD TSE Prion SkrantesjukeThis is the eighth case of the lethal deer disease in the area since the survey started in 2016.The reindeer cub was shot by a flock from the Norwegian National Guard, and the infectious agent was detected in the animal's lymph nodes.WEDNESDAY, NOVEMBER 01, 2017Norway detects CWD Skrantesjuke Deer possibly atypical Nor-98-type TSE?Greetings TSE prion world,i am seeing more and more references to the atypical Nor-98-type CWD TSE Prion in Norway as being of the non-infectious or non-infective variant. with science documented to date, i do not believe that any CWD Skrantesjuke TSE Prion typical or atypical in Norway or anywhere else can be classified as ''non-infective variant''. IF, Norway takes the USDA OIE views and makes atypical Nor-98 type CWD in Deer a International trading commodity fueled by junk science, as they did with sheep, i.e. no trade restrictions for Nor-98 in sheep, the world should then weep...terryNor-98 atypical Scrapie Transmission Studies Reviewsnip...see full text;FRIDAY, OCTOBER 13, 2017Norway, Two More New Cases of Chronic Wasting Disease CWD TSE Prion SkrantesjukeTUESDAY, OCTOBER 10, 2017Norway detects another case of CWD TSE PRION SkrantesjukeSATURDAY, SEPTEMBER 30, 2017Norway, CWD TSE Prion, Humans, Zoonosis, Fortsatt lite sannsynlig at mennesker kan smittes av skrantesyke?MONDAY, AUGUST 14, 2017NORWAY CWD, SHEEP GRAZING, and Scrapie, What If?TUESDAY, JUNE 20, 2017Norway Confirms 6th Case of Skrantesjuke CWD TSE Prion DiseaseTuesday, December 13, 2016Norway Chronic Wasting Disease CWD TSE Prion disease Skrantesjuke December 2016 UpdateThursday, September 22, 2016NORWAY DETECTS 5TH CASE OF CHRONIC WASTING DISEASE CWD TSE PRION SkrantesjukeSaturday, September 03, 2016NORWAY Regulation concerning temporary measures to reduce the spread of Chronic Wasting Disease (CWD) as 4th case of skrantesjuke confirmed in Sogn og FjordaneWednesday, August 31, 2016*** NORWAY CONFIRMS 4TH CASE OF CHRONIC WASTING DISEASE CWD TSE PRION IN SECOND CARIBOUWednesday, August 31, 2016NORWAY CONFIRMS 4TH CASE OF CHRONIC WASTING DISEASE CWD TSE PRION IN SECOND CARIBOUTuesday, August 02, 2016Chronic 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, 2016Norway reports a third case Chronic Wasting Disease CWD TSE Prion in 2nd Norwegian moose14/06/2016 - Norway reports a third caseTuesday, April 12, 2016The first detection of Chronic Wasting Disease (CWD) in Europe free-ranging reindeer from the Nordfjella population in South-Norway.Saturday, April 9, 2016The 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 AffairsSaturday, July 16, 2016Chronic wasting Disease in Deer (CWD or Spongiform Encephalopathy) The British Deer Society 07/04/2016Red Deer Ataxia or Chronic Wasting Disease CWD TSE PRION?could this have been cwd in the UK back in 1970’S ???Clinical Communication Enzootic ataxia in Red deerP.R. Wilson , Marjorie B. Orr & E.L. Key Pages 252-254 | Published online: 23 Feb 2011SEE FULL TEXT ;TUESDAY, DECEMBER 12, 2017Chronic Wasting Disease CWD TSE Prion (aka mad deer disease) Update USA December 14, 2017FRIDAY, DECEMBER 22, 2017Norway reports more cases of Chronic Wasting Disease CWD TSE Prion Skrantesjuke
2017
Subject: ***CDC Now Recommends Strongly consider having the deer or elk tested for CWD before you eat the meat
CDC Now Recommends Strongly consider having the deer or elk tested for CWD before you eat the meat
Chronic Wasting Disease (CWD)
Prevention
If CWD could spread to people, it would most likely be through eating of infected deer and elk. In a 2006-2007 CDC survey of U.S. residents, nearly 20 percent of those surveyed said they had hunted deer or elk and more than two-thirds said they had eaten venison or elk meat. However, to date, no CWD infections have been reported in people.
Hunters must consider many factors when determining whether to eat meat from deer and elk harvested from areas with CWD, including the level of risk they are willing to accept. Hunters harvesting wild deer and elk from areas with reported CWD should check state wildlife and public health guidance to see whether testing of animals is recommended or required in a given state or region. In areas where CWD is known to be present, CDC recommends that hunters strongly consider having those animals tested before eating the meat.
Tests for CWD are monitoring tools that some state wildlife officials use to look at the rates of CWD in certain animal populations. Testing may not be available in every state, and states may use these tests in different ways. A negative test result does not guarantee that an individual animal is not infected with CWD, but it does make it considerably less likely and may reduce your risk of exposure to CWD.
To be as safe as possible and decrease their potential risk of exposure to CWD, hunters should take the following steps when hunting in areas with CWD:
Do not shoot, handle or eat meat from deer and elk that look sick or are acting strangely or are found dead (road-kill). When field-dressing a deer: Wear latex or rubber gloves when dressing the animal or handling the meat. Minimize how much you handle the organs of the animal, particularly the brain or spinal cord tissues. Do not use household knives or other kitchen utensils for field dressing. Check state wildlife and public health guidance to see whether testing of animals is recommended or required. Recommendations vary by state, but information about testing is available from many state wildlife agencies. Strongly consider having the deer or elk tested for CWD before you eat the meat. If you have your deer or elk commercially processed, consider asking that your animal be processed individually to avoid mixing meat from multiple animals. If your animal tests positive for CWD, do not eat meat from that animal. The U.S. Department of Agriculture’s Animal and Plant Health Inspection Service regulates commercially farmed deer and elk. The agency operates a national CWD herd certification program. As part of the voluntary program, states and individual herd owners agree to meet requirements meant to decrease the risk of CWD in their herds. Privately owned herds that do not participate in the herd certification program may be at increased risk for CWD.
Page last reviewed: August 17, 2017 Page last updated: August 17, 2017 Content source: Centers for Disease Control and Prevention National Center for Emerging and Zoonotic Infectious Diseases (NCEZID) Division of High-Consequence Pathogens and Pathology (DHCPP)
> However, to date, no CWD infections have been reported in people.
key word here is 'reported'. science has shown that CWD in humans will look like sporadic CJD. SO, how can one assume that CWD has not already transmitted to humans? they can't, and it's as simple as that. from all recorded science to date, CWD has already transmitted to humans, and it's being misdiagnosed as sporadic CJD. ...terry
LOOKING FOR CWD IN HUMANS AS nvCJD or as an ATYPICAL CJD, LOOKING IN ALL THE WRONG PLACES $$$
*** These results would seem to suggest that CWD does indeed have zoonotic potential, at least as judged by the compatibility of CWD prions and their human PrPC target. Furthermore, extrapolation from this simple in vitro assay suggests that if zoonotic CWD occurred, it would most likely effect those of the PRNP codon 129-MM genotype and that the PrPres type would be similar to that found in the most common subtype of sCJD (MM1).***
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.
TUESDAY, SEPTEMBER 12, 2017
CDC Now Recommends Strongly consider having the deer or elk tested for CWD before you eat the meat
Prion 2017 Conference Abstracts CWD
2017 PRION CONFERENCE
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
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
Wednesday, May 24, 2017
PRION2017 CONFERENCE VIDEO UPDATE 23 – 26 May 2017 Edinburgh UPDATE 1
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
***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.***
*** Infectious agent of sheep scrapie may persist in the environment for at least 16 years ***
Gudmundur Georgsson1, Sigurdur Sigurdarson2 and Paul Brown3
Using in vitro prion replication for high sensitive detection of prions and prionlike proteins and for understanding mechanisms of transmission.
Claudio Soto
Mitchell Center for Alzheimer's diseases and related Brain disorders, Department of Neurology, University of Texas Medical School at Houston.
Prion and prion-like proteins are misfolded protein aggregates with the ability to selfpropagate to spread disease between cells, organs and in some cases across individuals. I n T r a n s m i s s i b l e s p o n g i f o r m encephalopathies (TSEs), prions are mostly composed by a misfolded form of the prion protein (PrPSc), which propagates by transmitting its misfolding to the normal prion protein (PrPC). The availability of a procedure to replicate prions in the laboratory may be important to study the mechanism of prion and prion-like spreading and to develop high sensitive detection of small quantities of misfolded proteins in biological fluids, tissues and environmental samples. Protein Misfolding Cyclic Amplification (PMCA) is a simple, fast and efficient methodology to mimic prion replication in the test tube. PMCA is a platform technology that may enable amplification of any prion-like misfolded protein aggregating through a seeding/nucleation process. In TSEs, PMCA is able to detect the equivalent of one single molecule of infectious PrPSc and propagate prions that maintain high infectivity, strain properties and species specificity. Using PMCA we have been able to detect PrPSc in blood and urine of experimentally infected animals and humans affected by vCJD with high sensitivity and specificity. Recently, we have expanded the principles of PMCA to amplify amyloid-beta (Aβ) and alphasynuclein (α-syn) aggregates implicated in Alzheimer's and Parkinson's diseases, respectively. Experiments are ongoing to study the utility of this technology to detect Aβ and α-syn aggregates in samples of CSF and blood from patients affected by these diseases.
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***Recently, we have been using PMCA to study the role of environmental prion contamination on the horizontal spreading of TSEs. These experiments have focused on the study of the interaction of prions with plants and environmentally relevant surfaces. Our results show that plants (both leaves and roots) bind tightly to prions present in brain extracts and excreta (urine and feces) and retain even small quantities of PrPSc for long periods of time. Strikingly, ingestion of prioncontaminated leaves and roots produced disease with a 100% attack rate and an incubation period not substantially longer than feeding animals directly with scrapie brain homogenate. Furthermore, plants can uptake prions from contaminated soil and transport them to different parts of the plant tissue (stem and leaves). Similarly, prions bind tightly to a variety of environmentally relevant surfaces, including stones, wood, metals, plastic, glass, cement, etc. Prion contaminated surfaces efficiently transmit prion disease when these materials were directly injected into the brain of animals and strikingly when the contaminated surfaces were just placed in the animal cage. These findings demonstrate that environmental materials can efficiently bind infectious prions and act as carriers of infectivity, suggesting that they may play an important role in the horizontal transmission of the disease.
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Since its invention 13 years ago, PMCA has helped to answer fundamental questions of prion propagation and has broad applications in research areas including the food industry, blood bank safety and human and veterinary disease diagnosis.
Friday, December 14, 2012
DEFRA U.K. What is the risk of Chronic Wasting Disease CWD being introduced into Great Britain? A Qualitative Risk Assessment October 2012
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In the USA, under the Food and Drug Administration's BSE Feed Regulation (21 CFR 589.2000) most material (exceptions include milk, tallow, and gelatin) from deer and elk is prohibited for use in feed for ruminant animals. With regards to feed for non-ruminant animals, under FDA law, CWD positive deer may not be used for any animal feed or feed ingredients. For elk and deer considered at high risk for CWD, the FDA recommends that these animals do not enter the animal feed system. However, this recommendation is guidance and not a requirement by law.
Animals considered at high risk for CWD include:
1) animals from areas declared to be endemic for CWD and/or to be CWD eradication zones and
2) deer and elk that at some time during the 60-month period prior to slaughter were in a captive herd that contained a CWD-positive animal.
Therefore, in the USA, materials from cervids other than CWD positive animals may be used in animal feed and feed ingredients for non-ruminants.
The amount of animal PAP that is of deer and/or elk origin imported from the USA to GB can not be determined, however, as it is not specified in TRACES. It may constitute a small percentage of the 8412 kilos of non-fish origin processed animal proteins that were imported from US into GB in 2011.
Overall, therefore, it is considered there is a __greater than negligible risk___ that (nonruminant) animal feed and pet food containing deer and/or elk protein is imported into GB.
There is uncertainty associated with this estimate given the lack of data on the amount of deer and/or elk protein possibly being imported in these products.
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36% in 2007 (Almberg et al., 2011). In such areas, population declines of deer of up to 30 to 50% have been observed (Almberg et al., 2011). In areas of Colorado, the prevalence can be as high as 30% (EFSA, 2011).
The clinical signs of CWD in affected adults are weight loss and behavioural changes that can span weeks or months (Williams, 2005). In addition, signs might include excessive salivation, behavioural alterations including a fixed stare and changes in interaction with other animals in the herd, and an altered stance (Williams, 2005). These signs are indistinguishable from cervids experimentally infected with bovine spongiform encephalopathy (BSE).
Given this, if CWD was to be introduced into countries with BSE such as GB, for example, infected deer populations would need to be tested to differentiate if they were infected with CWD or BSE to minimise the risk of BSE entering the human food-chain via affected venison.
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The rate of transmission of CWD has been reported to be as high as 30% and can approach 100% among captive animals in endemic areas (Safar et al., 2008).
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In summary, in endemic areas, there is a medium probability that the soil and surrounding environment is contaminated with CWD prions and in a bioavailable form. In rural areas where CWD has not been reported and deer are present, there is a greater than negligible risk the soil is contaminated with CWD prion.
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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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http://www.defra.gov.uk/animal-diseases/files/qra_chronic-wasting-disease-121029.pdf
TSS
Singeltary submission ;
Program Standards: Chronic Wasting Disease Herd Certification Program and Interstate Movement of Farmed or Captive Deer, Elk, and Moose
*** DOCUMENT ID: APHIS-2006-0118-0411
http://www.regulations.gov/#!documentDetail;D=APHIS-2006-0118-0411
http://chronic-wasting-disease.blogspot.com/2014/03/docket-no-00-108-10-chronic-wasting.html
DEFRA U.K. What is the risk of Chronic Wasting Disease CWD being introduced into Great Britain? A Qualitative Risk Assessment October 2012
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In the USA, under the Food and Drug Administration's BSE Feed Regulation (21 CFR 589.2000) most material (exceptions include milk, tallow, and gelatin) from deer and elk is prohibited for use in feed for ruminant animals. With regards to feed for non-ruminant animals, under FDA law, CWD positive deer may not be used for any animal feed or feed ingredients. For elk and deer considered at high risk for CWD, the FDA recommends that these animals do not enter the animal feed system. However, this recommendation is guidance and not a requirement by law.
Animals considered at high risk for CWD include:
1) animals from areas declared to be endemic for CWD and/or to be CWD eradication zones and
2) deer and elk that at some time during the 60-month period prior to slaughter were in a captive herd that contained a CWD-positive animal.
Therefore, in the USA, materials from cervids other than CWD positive animals may be used in animal feed and feed ingredients for non-ruminants.
The amount of animal PAP that is of deer and/or elk origin imported from the USA to GB can not be determined, however, as it is not specified in TRACES. It may constitute a small percentage of the 8412 kilos of non-fish origin processed animal proteins that were imported from US into GB in 2011.
Overall, therefore, it is considered there is a __greater than negligible risk___ that (nonruminant) animal feed and pet food containing deer and/or elk protein is imported into GB.
There is uncertainty associated with this estimate given the lack of data on the amount of deer and/or elk protein possibly being imported in these products.
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36% in 2007 (Almberg et al., 2011). In such areas, population declines of deer of up to 30 to 50% have been observed (Almberg et al., 2011). In areas of Colorado, the prevalence can be as high as 30% (EFSA, 2011).
The clinical signs of CWD in affected adults are weight loss and behavioural changes that can span weeks or months (Williams, 2005). In addition, signs might include excessive salivation, behavioural alterations including a fixed stare and changes in interaction with other animals in the herd, and an altered stance (Williams, 2005). These signs are indistinguishable from cervids experimentally infected with bovine spongiform encephalopathy (BSE).
Given this, if CWD was to be introduced into countries with BSE such as GB, for example, infected deer populations would need to be tested to differentiate if they were infected with CWD or BSE to minimise the risk of BSE entering the human food-chain via affected venison.
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The rate of transmission of CWD has been reported to be as high as 30% and can approach 100% among captive animals in endemic areas (Safar et al., 2008).
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In summary, in endemic areas, there is a medium probability that the soil and surrounding environment is contaminated with CWD prions and in a bioavailable form. In rural areas where CWD has not been reported and deer are present, there is a greater than negligible risk the soil is contaminated with CWD prion.
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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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http://www.defra.gov.uk/animal-diseases/files/qra_chronic-wasting-disease-121029.pdf
TSS
Singeltary submission ;
Program Standards: Chronic Wasting Disease Herd Certification Program and Interstate Movement of Farmed or Captive Deer, Elk, and Moose
*** DOCUMENT ID: APHIS-2006-0118-0411
http://www.regulations.gov/#!documentDetail;D=APHIS-2006-0118-0411
http://chronic-wasting-disease.blogspot.com/2014/03/docket-no-00-108-10-chronic-wasting.html
Back around 2000, 2001, or so, I was corresponding with officials abroad during the bse inquiry, passing info back and forth, and some officials from here inside USDA aphis FSIS et al. In fact helped me get into the USA 50 state emergency BSE conference call way back. That one was a doozy. But I always remember what “deep throat” I never knew who they were, but I never forgot;
Some unofficial information from a source on the inside looking out -
Confidential!!!!
As early as 1992-3 there had been long studies conducted on small pastures containing scrapie infected sheep at the sheep research station associated with the Neuropathogenesis Unit in Edinburgh, Scotland. Whether these are documented...I don't know. But personal recounts both heard and recorded in a daily journal indicate that leaving the pastures free and replacing the topsoil completely at least 2 feet of thickness each year for SEVEN years....and then when very clean (proven scrapie free) sheep were placed on these small pastures.... the new sheep also broke out with scrapie and passed it to offspring. I am not sure that TSE contaminated ground could ever be free of the agent!! A very frightening revelation!!!
---end personal email---end...tss
Some unofficial information from a source on the inside looking out -
Confidential!!!!
As early as 1992-3 there had been long studies conducted on small pastures containing scrapie infected sheep at the sheep research station associated with the Neuropathogenesis Unit in Edinburgh, Scotland. Whether these are documented...I don't know. But personal recounts both heard and recorded in a daily journal indicate that leaving the pastures free and replacing the topsoil completely at least 2 feet of thickness each year for SEVEN years....and then when very clean (proven scrapie free) sheep were placed on these small pastures.... the new sheep also broke out with scrapie and passed it to offspring. I am not sure that TSE contaminated ground could ever be free of the agent!! A very frightening revelation!!!
---end personal email---end...tss
Terry S. Singeltary Sr.
posted by Terry S. Singeltary Sr. at
11:39 AM
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