Norway Chronic Wasting Disease CWD TSE Prion Detected in Sixth Moose
New case of moose sickness 16.11.2019 18:59:08 CET | FSA
Test results from a self-killed elk found in Sigdal show that the animal had scabies (CWD).
This is the sixth case of moose disease in moose in Norway. The first five have been of the type of atypical tranquilizer that is considered not infectious. There were moose hunters who came randomly over the dead animal and who reported to the game manager in the municipality. Brain material was submitted to the Veterinary Institute for testing and this resulted in ailment. In animals with atypical scabies, we do not find any infectious agent in the lymph nodes, nor was it done in the head lymph nodes from this moose. The Norwegian Food Safety Authority now sends the rest of the animal to the Veterinary Institute for further testing.
Report whether you see sick or dead deer Since its inception in 2016, over 94,000 deer have been tested for aphid disease. The Norwegian Food Safety Authority encourages anyone traveling in the woods and fields to see sick or dead deer to report to the Food Safety Authority. Symptoms of jaundice are emaciation, frequent urination and abnormal behavior, such as animals not shaming humans. The disease is deadly to deer, but has never been shown to infect humans, either from animals or meat.
Two variants of the apex There are two variants of the apex, one infectious variant and one variant which we assume is not contagious. The infectious variant is only found on wild reindeer in Nordfjella. Atypical ridge disease has previously been found on five moose; three in Selbu, one in Lierne and one in Flesberg, in addition to a deer in Gjemnes.
NYTT TILFELLE AV SKRANTESJUKE PÅ ELG
Prøveresultater fra en selvdød elg funnet i Sigdal viser at dyret hadde skrantesjuke (CWD).
Det sjette tilfellet av skrantesjuke hos elg er oppdaget i Norge. Trolig dreier det seg også denne gangen om atypisk skrantesjuke. Arkivfoto: Erling J. Solberg, NINA
Dette er det sjette tilfellet av skrantesjuke hos elg i Norge. De fem første har vært av typen atypisk skrantesjuke som blir ansett ikke å smitte. Det var elgjegere som kom tilfeldig over det døde dyret og som meldte fra til viltforvalter i kommunen. Hjernemateriale ble sendt inn til Veterinærinstituttet for testing, og det ga utslag på skrantesjuke. Hos dyr med atypisk skrantesjuke finner vi ikke smittestoff i lymfeknutene, og det ble det heller ikke gjort i hodelymfeknutene fra denne elgen. Mattilsynet sender nå resten av dyret inn til Veterinærinstituttet for videre testing.
Meld fra om du ser syke eller døde hjortedyr
Siden starten i 2016 er over 94 000 hjortedyr testet for skrantesjuke. Mattilsynet oppfordrer alle som ferdes i skog og mark og ser syke eller døde hjortedyr om å melde fra til Mattilsynet. Symptomer på skrantesjuke er avmagring, hyppig urinering og unormal oppførsel, for eksempel at dyr ikke skyr mennesker.
Sykdommen er dødelig for hjortedyr, men har aldri vist seg å smitte til mennesker, hverken fra dyr eller kjøtt.
To varianter av skrantesjuke
Det finnes to varianter av skrantesjuke, en smittsom variant og en variant som vi antar ikke er smittsom. Den smittsomme varianten er kun funnet på villrein i Nordfjella. Atypisk skrantesjuke er fra før blitt funnet på fem elger; tre i Selbu, en i Lierne og en i Flesberg, i tillegg til en hjort i Gjemnes.
The new type of chronic illness (Chronic Wasting Disease, CWD) has been called Nor16CWD. The article contains a description of the three cases of CWD found on moose in Norway and how they are different from those of reindeer, CWD in North America and other prion diseases in animals.
In the understanding of discoveries in Norwegian moose, we build on knowledge of similar disease in cattle (BSE) and sheep (scrapie disease). In these animals there is variety that makes us distinguish between classic and atypical disease. The Veterinary Institute, with Benestad, was central to the discovery of atypical scrapie disease in sheep, named Nor98 after discovery this year. This is a disease that has not been contagious, such as classic scrapie. In cattle, atypical bullet disease (BSE) was discovered in 2003. Atypical BSE and Nor98 are thought to occur spontaneously, especially in older animals. Knowledge of variation in prion diseases has led to different management and management of the different types.
- Since we now gain new knowledge about variation in this disease group also in our deer animals, it can have consequences for future professional councils, and management says senior scientist Sylvie Benestad.
Different clearly from other CWD types The new discovery Nor16CWD is shown, among other things, by the way the misfolded prion protein is distributed in the brain of the moose. This is clearly different from the other CWD types. The structure of the protein itself is also different. Nor16CWD has been detected only in the brain and not in lymph nodes, which is common with other types of CWD. The moose have been 13-14 years old, while other types of CWD are found on far younger animals. In the case of Norwegian wild reindeer and deer in North America, CWD has been contagious. Such a characteristic of classic CWD is probably linked to the distribution of infectious agents to lymph nodes in the body, in addition to the brain. Based on the work done in connection with this article, it is not possible to say whether the new type of CWD in elk is contagious between deer. Number of moose tested,
Behind the scientific publication is a wide-ranging international team of researchers from Italy, Norway, the United States, Canada, and France.
Read article
A novel type of Chronic Wasting Disease detected in European moose ( Alces alces ) in Norway
Volume 24, Number 12—December 2018 Research Novel Type of Chronic Wasting Disease Detected in Moose (Alces alces), Norway
THURSDAY, SEPTEMBER 26, 2019
Sweden The third case of CWD in moose in Arjeplog is now established
SATURDAY, MARCH 10, 2018
FINLAND REPORTS FIRST CASE OF CHRONIC WASTING DISEASE CWD TSE PRION IN A moose or European elk (Alces alces)
***> Two variants of the apex There are two variants of the apex, one infectious variant and one variant which we assume is not contagious.
***> one variant which we assume is not contagious.
what kind of BS Junk Science is this? please tell me?
do we NOW 'ASSUME' science and make regulations there from?
to assume that a dangerous pathogen is NOT contagious, and then make regulations there from, is absolutely not scientific, it's what i call 'for profit' science, or junk science $
but, on the other hand we have;
''The NA elk, however, is in-between, with a low amounts of abnormal PrP deposition (Race et al., 2007) associated with longer incubation periods (Moore et al., 2018) and low prevalence (Mysterud and Edmunds, 2019).''
so, lives longer in the environment, has longer to spread the tse prion agent.
look, it's either a Transmissible Spongiform Encephalopathy TSE Prion disease, or it's not.
a very dangerous precedent has been set $$$
this reminds me of ;
IBNC BSE TSE Prion mad cow disease
***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 Terry S. Singeltary Sr. on 03 Jul 2015 at 16:53 GMT
*** Singeltary reply ; Molecular, Biochemical and Genetic Characteristics of BSE in Canada Singeltary reply
ADOPTED: 26 September 2019
doi: 10.2903/j.efsa.2019.5863
Update on chronic wasting disease (CWD) III EFSA Panel on Biological Hazards (BIOHAZ),
Kostas Koutsoumanis, Ana Allende, Avelino Alvarez-Ordonez, Declan Bolton, Sara Bover-Cid, Marianne Chemaly, Robert Davies, Alessandra De Cesare, Lieve Herman, Friederike Hilbert, Roland Lindqvist, Maarten Nauta, Luisa Peixe, Giuseppe Ru, Panagiotis Skandamis, Elisabetta Suffredini, Olivier Andreoletti, Sylvie L Benestad, Emmanuel Comoy, Romolo Nonno, Teresa da Silva Felicio, Angel Ortiz-Pelaez and Marion M Simmons
snip...
3.6.1. Scenario development
The description of the current scientific evidence on the characteristics of European CWD isolates (see Section 3.1) has implications for their potential capacity to spread naturally within cervid populations. In particular, the presence/absence of detectable PrPSc outside the CNS is thought to be an indication of the probability of spread under field conditions. While CNS involvement is a consistent feature of all clinical TSE cases regardless of species, the presence or absence of detectable PrPSc in peripheral tissues is more of a continuum, with some phenotypes presenting early accumulations of PrPSc, while others only accumulate limited amounts, or none. These differences may be associated either with strain or host genotype, or a combination of the two (for recent review of the cervid context, see Section 3.2.2 of the EFSA BIOHAZ Panel, 2018). For example, most cases of classical scrapie and NA CWD have widespread peripheral tissue involvement, the extent of which is affected by genotype and both are contagious under field conditions. BSE, H- and L-type BSE and atypical/Nor98 scrapie, conversely, have little or no detectable PrPSc in peripheral tissues (Benestad et al., 2003; Wells et al., 2005; Andreoletti et al., 2011; Stack et al., 2011; EFSA, 2014) and tend to present as individual
Chronic Wasting Disease (CWD) III www.efsa.europa.eu/efsajournal 36 EFSA Journal 2019;17(11):5863
cases within herds/flocks. (It is important to note that while the term ‘atypical’ is often applied to this latter phenotype, this does not mean that they necessarily share the same biochemical or biological properties, or zoonotic potential; see Appendix A.5) The NA elk, however, is in-between, with a low amounts of abnormal PrP deposition (Race et al., 2007) associated with longer incubation periods (Moore et al., 2018) and low prevalence (Mysterud and Edmunds, 2019). These differences allow the description for developing hypothetical epidemiological scenarios of what can be considered representative of the extremes of this phenotypic spectrum:
• A contagious form presenting with peripheral distribution of PrPSc/infectivity, similar to the wellknown presentation of CWD in NA and classical scrapie in small ruminants with susceptible PrP genotypes. It is assumed, for this scenario, that infected animals would be able to transmit disease horizontally under field conditions and that infection could also be spread via environmental contamination by either live animals (e.g. through saliva, urine, faeces) or carcass disintegration. Subsequent dissemination could occur as a result of human activity, fomites and/ or scavengers or via the feed chain.
• A non-contagious form presenting little or no detectable involvement of peripheral tissues, akin to BSE in cattle or atypical/Nor98 scrapie in small ruminants. It is assumed, for this scenario, that infection would be less likely to transmit horizontally under field conditions and that environmental contamination by live animals would be minimal. Environmental contamination could still arise from the CNS of disintegrating carcasses and be spread via human activity, fomites and/or scavengers or via the feed chain.
Disease can spread by:
• extending the geographic extent of a focus to a new area/region/country: mainly by natural migration of infected animals and by the translocation of infected cervids by humans; • once introduced into a herd or population, the local spread of the agent is associated with the rate of contacts between animals or the environmental contamination. Behavioural and social factors of the different susceptible and non-susceptible species present explain the transmission rate of the disease and the consequent spread to non-infected animals within the population of interest.
In both cases, the agent(s) must be released from the infected individual(s), hence allowing other non-infected animals to be exposed resulting in further release or translocation and giving rise to:
• a new individual being infected that, if it is of a susceptible species, will develop clinical disease and will be capable of shedding infectivity in excreta throughout most of the incubation period if the disease phenotype includes PrP accumulation in peripheral tissues
• a subclinical or carrier animal, in which some abnormal PrP accumulates, but the animal does not develop clinical disease within its lifetime. Such animals may or may not shed infectivity in excreta, potentially over prolonged periods.
• a passive carrier, in which infection does not establish itself and infected material passes through the gut and into the environment via faeces in a relatively short time postconsumption (e.g. non-susceptible species such as predators, scavengers and carrion birds)
The two working scenarios may or not reflect the ability and the extent to which any of them can contribute to the transmission and spread of the disease. These scenarios do not account either for the possibility of the biological properties of an isolate changing on passage through another host species (EFSA BIOHAZ Panel, 2015).
Incomplete inactivation of atypical scrapie following recommended autoclave decontamination procedures
First published: 21 May 2019
This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/tbed.13247
Summary
Prions are highly resistant to the decontamination procedures normally used to inactivate conventional pathogens. This is a challenging problem not only in the medical and veterinary fields for minimising the risk of transmission from potentially infective sources, but also for ensuring the safe disposal or subsequent use of animal by‐products. Specific pressure autoclaving protocols were developed for this purpose, but different strains of prions have been reported to have differing resistance patterns to established prion decontamination procedures, and as additional TSE strains are identified it is necessary to determine the effectiveness of such procedures. In this study we assessed the efficacy of sterilisation using the EU recommended autoclave procedure for prions (133o C, 3 Bar for 20 min) on the atypical or Nor98 (AS/Nor98) scrapie strain of sheep and goats. Using a highly sensitive murine mouse model (tg338) that overexpresses ovine PrPC, we determined that this method of decontamination reduced the infectivity titre by 1010. Infectivity was nonetheless still detected after applying the recommended autoclaving protocol. This shows that AS/Nor98 can survive the designated legislative decontamination conditions, albeit with a significant decrease in titre. The infectivity of a classical scrapie isolate subjected to the same decontamination conditions was reduced by 106 suggesting that the AS/Nor98 isolate is less sensitive to decontamination than the classical scrapie source.
This article is protected by copyright. All rights reserved.
A newly identified type of scrapie agent can naturally infect sheep with resistant PrP genotypes
Annick Le Dur*,?, Vincent Béringue*,?, Olivier Andréoletti?, Fabienne Reine*, Thanh Lan Laï*, Thierry Baron§, Bjørn Bratberg¶, Jean-Luc Vilotte?, Pierre Sarradin**, Sylvie L. Benestad¶, and Hubert Laude*,?? +Author Affiliations
*Virologie Immunologie Moléculaires and ?Génétique Biochimique et Cytogénétique, Institut National de la Recherche Agronomique, 78350 Jouy-en-Josas, France; ?Unité Mixte de Recherche, Institut National de la Recherche Agronomique-Ecole Nationale Vétérinaire de Toulouse, Interactions Hôte Agent Pathogène, 31066 Toulouse, France; §Agence Française de Sécurité Sanitaire des Aliments, Unité Agents Transmissibles Non Conventionnels, 69364 Lyon, France; **Pathologie Infectieuse et Immunologie, Institut National de la Recherche Agronomique, 37380 Nouzilly, France; and ¶Department of Pathology, National Veterinary Institute, 0033 Oslo, Norway
***Edited by Stanley B. Prusiner, University of California, San Francisco, CA (received for review March 21, 2005)
Abstract
Scrapie in small ruminants belongs to transmissible spongiform encephalopathies (TSEs), or prion diseases, a family of fatal neurodegenerative disorders that affect humans and animals and can transmit within and between species by ingestion or inoculation. Conversion of the host-encoded prion protein (PrP), normal cellular PrP (PrPc), into a misfolded form, abnormal PrP (PrPSc), plays a key role in TSE transmission and pathogenesis. The intensified surveillance of scrapie in the European Union, together with the improvement of PrPSc detection techniques, has led to the discovery of a growing number of so-called atypical scrapie cases. These include clinical Nor98 cases first identified in Norwegian sheep on the basis of unusual pathological and PrPSc molecular features and "cases" that produced discordant responses in the rapid tests currently applied to the large-scale random screening of slaughtered or fallen animals. Worryingly, a substantial proportion of such cases involved sheep with PrP genotypes known until now to confer natural resistance to conventional scrapie. Here we report that both Nor98 and discordant cases, including three sheep homozygous for the resistant PrPARR allele (A136R154R171), efficiently transmitted the disease to transgenic mice expressing ovine PrP, and that they shared unique biological and biochemical features upon propagation in mice.
*** These observations support the view that a truly infectious TSE agent, unrecognized until recently, infects sheep and goat flocks and may have important implications in terms of scrapie control and public health.
OR
***The pathology features of Nor98 in the cerebellum of the affected sheep showed similarities with those of sporadic Creutzfeldt-Jakob disease in humans.
OR
*** Intriguingly, these conclusions suggest that some pathological features of Nor98 are reminiscent of Gerstmann-Sträussler-Scheinker disease.
OR here;
*** The discovery of previously unrecognized prion diseases in both humans and animals (i.e., Nor98 in small ruminants) demonstrates that the range of prion diseases might be wider than expected and raises crucial questions about the epidemiology and strain properties of these new forms. We are investigating this latter issue by molecular and biological comparison of VPSPr, GSS and Nor98.
VARIABLY PROTEASE-SENSITVE PRIONOPATHY IS TRANSMISSIBLE ...price of prion poker goes up again $
OR-10: Variably protease-sensitive prionopathy is transmissible in bank voles
Romolo Nonno,1 Michele Di Bari,1 Laura Pirisinu,1 Claudia D’Agostino,1 Stefano Marcon,1 Geraldina Riccardi,1 Gabriele Vaccari,1 Piero Parchi,2 Wenquan Zou,3 Pierluigi Gambetti,3 Umberto Agrimi1 1Istituto Superiore di Sanità; Rome, Italy; 2Dipartimento di Scienze Neurologiche, Università di Bologna; Bologna, Italy; 3Case Western Reserve University; Cleveland, OH USA
Background. Variably protease-sensitive prionopathy (VPSPr) is a recently described “sporadic”neurodegenerative disease involving prion protein aggregation, which has clinical similarities with non-Alzheimer dementias, such as fronto-temporal dementia. Currently, 30 cases of VPSPr have been reported in Europe and USA, of which 19 cases were homozygous for valine at codon 129 of the prion protein (VV), 8 were MV and 3 were MM. A distinctive feature of VPSPr is the electrophoretic pattern of PrPSc after digestion with proteinase K (PK). After PK-treatment, PrP from VPSPr forms a ladder-like electrophoretic pattern similar to that described in GSS cases. The clinical and pathological features of VPSPr raised the question of the correct classification of VPSPr among prion diseases or other forms of neurodegenerative disorders. Here we report preliminary data on the transmissibility and pathological features of VPSPr cases in bank voles.
Materials and Methods. Seven VPSPr cases were inoculated in two genetic lines of bank voles, carrying either methionine or isoleucine at codon 109 of the prion protein (named BvM109 and BvI109, respectively). Among the VPSPr cases selected, 2 were VV at PrP codon 129, 3 were MV and 2 were MM. Clinical diagnosis in voles was confirmed by brain pathological assessment and western blot for PK-resistant PrPSc (PrPres) with mAbs SAF32, SAF84, 12B2 and 9A2.
Results. To date, 2 VPSPr cases (1 MV and 1 MM) gave positive transmission in BvM109. Overall, 3 voles were positive with survival time between 290 and 588 d post inoculation (d.p.i.). All positive voles accumulated PrPres in the form of the typical PrP27–30, which was indistinguishable to that previously observed in BvM109 inoculated with sCJDMM1 cases.
In BvI109, 3 VPSPr cases (2 VV and 1 MM) showed positive transmission until now. Overall, 5 voles were positive with survival time between 281 and 596 d.p.i.. In contrast to what observed in BvM109, all BvI109 showed a GSS-like PrPSc electrophoretic pattern, characterized by low molecular weight PrPres. These PrPres fragments were positive with mAb 9A2 and 12B2, while being negative with SAF32 and SAF84, suggesting that they are cleaved at both the C-terminus and the N-terminus. Second passages are in progress from these first successful transmissions.
Conclusions. Preliminary results from transmission studies in bank voles strongly support the notion that VPSPr is a transmissible prion disease. Interestingly, VPSPr undergoes divergent evolution in the two genetic lines of voles, with sCJD-like features in BvM109 and GSS-like properties in BvI109.
The discovery of previously unrecognized prion diseases in both humans and animals (i.e., Nor98 in small ruminants) demonstrates that the range of prion diseases might be wider than expected and raises crucial questions about the epidemiology and strain properties of these new forms. We are investigating this latter issue by molecular and biological comparison of VPSPr, GSS and Nor98.
WEDNESDAY, OCTOBER 16, 2019
***> Australia Assessment of bulk wheat from Canada Part B: Animal biosecurity risk advice, CWD TSE Prion concerns are mounting
***> cattle, pigs, sheep, cwd, tse, prion, oh my!
***> In contrast, cattle are highly susceptible to white-tailed deer CWD and mule deer CWD in experimental conditions but no natural CWD infections in cattle have been reported (Sigurdson, 2008; Hamir et al., 2006).
Sheep and cattle may be exposed to CWD via common grazing areas with affected deer but so far, appear to be poorly susceptible to mule deer CWD (Sigurdson, 2008). In contrast, cattle are highly susceptible to white-tailed deer CWD and mule deer CWD in experimental conditions but no natural CWD infections in cattle have been reported (Sigurdson, 2008; Hamir et al., 2006). It is not known how susceptible humans are to CWD but given that the prion can be present in muscle, it is likely that humans have been exposed to the agent via consumption of venison (Sigurdson, 2008). Initial experimental research suggests that human susceptibility to CWD is low and there may be a robust species barrier for CWD transmission to humans (Sigurdson, 2008), however the risk appetite for a public health threat may still find this level unacceptable.
cwd scrapie pigs oral routes
***> However, at 51 months of incubation or greater, 5 animals were positive by one or more diagnostic methods. Furthermore, positive bioassay results were obtained from all inoculated groups (oral and intracranial; market weight and end of study) suggesting that swine are potential hosts for the agent of scrapie. <***
>*** Although the current U.S. feed ban is based on keeping tissues from TSE infected cattle from contaminating animal feed, swine rations in the U.S. could contain animal derived components including materials from scrapie infected sheep and goats. These results indicating the susceptibility of pigs to sheep scrapie, coupled with the limitations of the current feed ban, indicates that a revision of the feed ban may be necessary to protect swine production and potentially human health. <***
***> Results: PrPSc was not detected by EIA and IHC in any RPLNs. All tonsils and MLNs were negative by IHC, though the MLN from one pig in the oral <6 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.
Friday, December 14, 2012
DEFRA U.K. What is the risk of Chronic Wasting Disease CWD being introduced into Great Britain? A Qualitative Risk Assessment October 2012
snip.....
In the USA, under the Food and Drug Administration's BSE Feed Regulation (21 CFR 589.2000) most material (exceptions include milk, tallow, and gelatin) from deer and elk is prohibited for use in feed for ruminant animals. With regards to feed for non-ruminant animals, under FDA law, CWD positive deer may not be used for any animal feed or feed ingredients. For elk and deer considered at high risk for CWD, the FDA recommends that these animals do not enter the animal feed system. However, this recommendation is guidance and not a requirement by law. Animals considered at high risk for CWD include:
1) animals from areas declared to be endemic for CWD and/or to be CWD eradication zones and
2) deer and elk that at some time during the 60-month period prior to slaughter were in a captive herd that contained a CWD-positive animal.
Therefore, in the USA, materials from cervids other than CWD positive animals may be used in animal feed and feed ingredients for non-ruminants.
The amount of animal PAP that is of deer and/or elk origin imported from the USA to GB can not be determined, however, as it is not specified in TRACES.
It may constitute a small percentage of the 8412 kilos of non-fish origin processed animal proteins that were imported from US into GB in 2011.
Overall, therefore, it is considered there is a __greater than negligible risk___ that (nonruminant) animal feed and pet food containing deer and/or elk protein is imported into GB.
There is uncertainty associated with this estimate given the lack of data on the amount of deer and/or elk protein possibly being imported in these products.
snip.....
36% in 2007 (Almberg et al., 2011). In such areas, population declines of deer of up to 30 to 50% have been observed (Almberg et al., 2011). In areas of Colorado, the prevalence can be as high as 30% (EFSA, 2011). The clinical signs of CWD in affected adults are weight loss and behavioural changes that can span weeks or months (Williams, 2005). In addition, signs might include excessive salivation, behavioural alterations including a fixed stare and changes in interaction with other animals in the herd, and an altered stance (Williams, 2005). These signs are indistinguishable from cervids experimentally infected with bovine spongiform encephalopathy (BSE). Given this, if CWD was to be introduced into countries with BSE such as GB, for example, infected deer populations would need to be tested to differentiate if they were infected with CWD or BSE to minimise the risk of BSE entering the human food-chain via affected venison. snip..... The rate of transmission of CWD has been reported to be as high as 30% and can approach 100% among captive animals in endemic areas (Safar et al., 2008).
snip.....
In summary, in endemic areas, there is a medium probability that the soil and surrounding environment is contaminated with CWD prions and in a bioavailable form. In rural areas where CWD has not been reported and deer are present, there is a greater than negligible risk the soil is contaminated with CWD prion. snip..... In summary, given the volume of tourists, hunters and servicemen moving between GB and North America, the probability of at least one person travelling to/from a CWD affected area and, in doing so, contaminating their clothing, footwear and/or equipment prior to arriving in GB is greater than negligible... For deer hunters, specifically, the risk is likely to be greater given the increased contact with deer and their environment. However, there is significant uncertainty associated with these estimates.
snip.....
Therefore, it is considered that farmed and park deer may have a higher probability of exposure to CWD transferred to the environment than wild deer given the restricted habitat range and higher frequency of contact with tourists and returning GB residents.
snip.....
***> READ THIS VERY, VERY, CAREFULLY, AUGUST 1997 MAD COW FEED BAN WAS A SHAM, AS I HAVE STATED SINCE 1997! 3 FAILSAFES THE FDA ET AL PREACHED AS IF IT WERE THE GOSPEL, IN TERMS OF MAD COW BSE DISEASE IN USA, AND WHY IT IS/WAS/NOT A PROBLEM FOR THE USA, and those are;
BSE TESTING (failed terribly and proven to be a sham)
BSE SURVEILLANCE (failed terribly and proven to be a sham)
BSE 589.2001 FEED REGULATIONS (another colossal failure, and proven to be a sham)
these are facts folks. trump et al just admitted it with the feed ban.
see;
FDA Reports on VFD Compliance
John Maday
August 30, 2019 09:46 AM VFD-Form 007 (640x427)
Before and after the current Veterinary Feed Directive rules took full effect in January, 2017, the FDA focused primarily on education and outreach. ( John Maday ) Before and after the current Veterinary Feed Directive (VFD) rules took full effect in January, 2017, the FDA focused primarily on education and outreach to help feed mills, veterinarians and producers understand and comply with the requirements. Since then, FDA has gradually increased the number of VFD inspections and initiated enforcement actions when necessary. On August 29, FDA released its first report on inspection and compliance activities. The report, titled “Summary Assessment of Veterinary Feed Directive Compliance Activities Conducted in Fiscal Years 2016 – 2018,” is available online.
SUNDAY, SEPTEMBER 1, 2019
***> FDA Reports on VFD Compliance
TUESDAY, OCTOBER 29, 2019
America BSE 589.2001 FEED REGULATIONS, BSE SURVEILLANCE, BSE TESTING, and CJD TSE Prion
FRIDAY, NOVEMBER 15, 2019
Southwest Wisconsin CWD, Deer and Predator Study
FRIDAY, OCTOBER 25, 2019
Experts testify United States is underprepared for bioterrorism threats Transmissible Spongiform Encephalopathy TSE Prion disease
Subject: EFSA Panel on Biological Hazards (BIOHAZ) Update on chronic wasting disease (CWD) III
Update on chronic wasting disease (CWD) III
EFSA Panel on Biological Hazards (BIOHAZ),
Kostas Koutsoumanis, Ana Allende, Avelino Alvarez-Ordonez, Declan Bolton, Sara Bover-Cid, Marianne Chemaly, Robert Davies, Alessandra De Cesare, Lieve Herman, Friederike Hilbert, Roland Lindqvist, Maarten Nauta, Luisa Peixe, Giuseppe Ru, Panagiotis Skandamis, Elisabetta Suffredini, Olivier Andreoletti, Sylvie L Benestad, Emmanuel Comoy, Romolo Nonno, Teresa da Silva Felicio, Angel Ortiz-Pelaez and Marion M Simmons
Abstract
The European Commission asked EFSA for a Scientific Opinion: to revise the state of knowledge about the differences between the chronic wasting disease (CWD) strains found in North America (NA) and Europe and within Europe; to review new scientific evidence on the zoonotic potential of CWD and to provide recommendations to address the potential risks and to identify risk factors for the spread of CWD in the European Union. Full characterisation of European isolates is being pursued, whereas most NA CWD isolates have not been characterised in this way. The differing surveillance programmes in these continents result in biases in the types of cases that can be detected. Preliminary data support the contention that the CWD strains identified in Europe and NA are different and suggest the presence of strain diversity in European cervids. Current data do not allow any conclusion on the implications of strain diversity on transmissibility, pathogenesis or prevalence. Available data do not allow any conclusion on the zoonotic potential of NA or European CWD isolates. The risk of CWD to humans through consumption of meat cannot be directly assessed. At individual level, consumers of meat, meat products and offal derived from CWD-infected cervids will be exposed to the CWD agent(s). Measures to reduce human dietary exposure could be applied, but exclusion from the food chain of whole carcasses of infected animals would be required to eliminate exposure. Based on NA experiences, all the risk factors identified for the spread of CWD may be associated with animals accumulating infectivity in both the peripheral tissues and the central nervous system. A subset of risk factors is relevant for infected animals without involvement of peripheral tissues. All the risk factors should be taken into account due to the potential co-localisation of animals presenting with different disease phenotypes.
© 2019 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.
Keywords: chronic, wasting, cervids, strain, risk, zoonotic
Requestor: European Commission
Question number: EFSA-Q-2018-00763
Correspondence: biohaz@efsa.europa.eu
Summary
In 2018, the European Food Safety Authority (EFSA) was asked by the European Commission to deliver a Scientific Opinion on three Terms of Reference (ToRs) related to chronic wasting disease (CWD): (ToR1) to revise the state of knowledge, considering new scientific data, about the differences: a) between the strains found in different species in North America (NA) and in Europe and b) between the strains found so far in moose, reindeer and red deer in Europe, with the main emphasis on transmissibility (transmission paths), pathogenicity and prevalence of the different strains and susceptibility of the different species/genotypes; (ToR2) to revise the new scientific evidence on the zoonotic potential of CWD, to assess the risk of transmission to humans through the consumption of fresh meat, meat products and offal of cervids and to provide recommendations on possible additional control measures to address the risks identified; and (ToR3) to identify risk factors that can facilitate the spread of CWD in the European Union given the current situation of the disease.
To source the relevant data, the extensive literature searches used in the previous recent EFSA Scientific Opinions on CWD (EFSA BIOHAZ Panel, 2017, 2018) were updated. In addition, research groups known to be conducting bioassay transmission studies and molecular/biochemical studies (protein misfolding cyclic amplification (PMCA), real-time quaking-induced conversion (RT-QuIC), PrPres typing, conformational stability, proteinase K (PK) resistance, etc.) to characterise and the transmissibility of CWD field isolates from cases confirmed in Norway/Finland and in NA were asked to provide additional pre-publication data. Regarding risk factors, the strength of the evidence for the causal role of each factor was appraised, based on study design and a score-based ranking from the strongest evidence (intervention studies) to the weakest (theoretical biological plausibility) was applied. Full characterisation of European isolates is being pursued through the collection of data on host species spectrum and genotype, clinical presentation, histopathology, immunopathology, tissue distribution, pathogenesis, the biochemical properties of the PrPSc, and bioassay through experimental transmission to a wide range of rodent models, whereas most NA CWD isolates have not been fully characterised in this way. However, preliminary data support the contention that the CWD strains identified to date in Europe and NA are different and suggest the presence of strain diversity in the European cervid population. The origin(s) of CWD in Europe remains unknown, and while it is clear that the disease identified in the reindeer in Nordfjella is contagious, the nature of the prion disease in the other species (the European moose and red deer) is still to be established.
NA CWD has been transmitted experimentally to cattle and sheep, but with incomplete attack rates. The species barrier appears higher for pigs, although challenged animals can support low-level prion amplification. Experimental transmission to transgenic (tg) mice and other rodent models shows some difference in the host ranges of different isolates but, particularly for the European isolates, many bioassays are still ongoing and data are not yet available. The number of strains, the strain diversity, the prevalence and the potential host range of disease in both NA and Europe CWD may all be underestimated.
In vitro studies suggest that CWD isolates derived from experimentally challenged reindeer, and elk with a specific PRNP polymorphism (132 MM) would present an intermediate potential of conversion of human PrP to disease-associated PrPSc. Some studies have shown that exposure to some NA CWD isolates can result in the conversion of human PrP in vitro and that some NA CWD isolates can transmit disease efficiently to squirrel monkeys. However, in vivo studies performed with humanised mice and macaques are considered to be the most pertinent models of human susceptibility and there is conflicting evidence on the transmissibility of NA CWD isolates in these models.
Epidemiological studies suffer from many methodological limitations and logistic constraints and some of them are still ongoing in NA but, until now, there is no epidemiological evidence of NA CWD causing disease in humans. The risk to humans through consumption of meat, meat products and offal derived from CWD-infected cervids cannot be directly assessed. At individual level, consumers of meat, meat products and offal derived from CWD-infected cervids will be exposed to the CWD agent(s). At the population level, the probability of exposure via consumption of venison depends on the prevalence of CWD agent(s) in each of the species that are consumed (reindeer, moose, red deer), which is not known. Preliminary testing of animals intended for human consumption with removal of any carcases that test positive, or the removal of high-risk tissues from cervids intended for human consumption, or the combination of these measures, would reduce the probability of dietary exposure of humans to the CWD agent(s). The prohibition of harvesting/hunting susceptible species in infected premises/areas could also be considered as a preventive measure.
Chronic Wasting Disease (CWD) III
www.efsa.europa.eu/efsajournal 3 EFSA Journal 2019;17(11):5863
Current EU legislation requires a 3-year monitoring programme for CWD from 1 January 2018 to 31 December 2020 to be implemented in six Member States (MSs) that have a wild and/or farmed and/or semi-domesticated population of moose and/or reindeer: Estonia, Finland, Latvia, Lithuania, Poland and Sweden. In 2018, the six MS tested a total 5,110 cervids, of which 4,674 (91.5%) were wild animals, mostly roe deer and red deer, and 436 (8.5%) were captive, farmed or semi-domesticated, with more than half of them being semi-domesticated reindeer tested in Finland. Over 59% of all cervids tested were from healthy hunted/slaughtered fit for human consumption animals, whose probability of disease is lower than that of sick animals, road kills or fallen stock. Up to 20 September 2019, 28 cases have been reported in Europe: 19 wild reindeer, 4 moose and one red deer in Norway, one moose in Finland and three moose in Sweden.
Using data from the NA CWD experience, 13 groups of risk factors have been identified based on their biological plausibility to spread CWD. Some of these are supported by epidemiological evidence from NA CWD studies with variable strength of evidence after applying the score-based ranking, while others remain hypothetical:
1) Natural movement of live wild deer from infected areas,
2) Man-mediated movement of live farmed/free-ranging deer from infected areas,
3) Failure to separate live farmed and free-ranging deer,
4) High deer density,
5) Species-specific social organisation,
6) Sex-related behaviours,
7) Natural or man-mediated animal aggregation,
8) Consumption of forage grown on contaminated soil,
9) Fallen stock or inappropriate disposal of carcasses and slaughter by-products,
10) Movement of other animals (working dogs, scavengers, predators),
11) Transfer of inanimate vehicles of contamination (fomites),
12) Environmental persistence of prions,
13) Host genetics.
All the identified risk factors may contribute to the spread of the disease when it is associated with the accumulation of infectivity in peripheral tissues, a host phenotype that is compatible with a contagious disease. A subset of risk factors (1, 2, 6, 8, 9, 10, 11, 12 and 13) is relevant to cases of disease that do not involve peripheral accumulation of infectivity and are therefore less contagious or non-contagious and may contribute to the spread of the disease mainly via environmental contamination following death. Some risk factors are man-mediated and are considered preventable. Their management could contribute to the decrease in the theoretical risk of spread of CWD. The potential co-localisation of cervid species and disease phenotypes mean that all the identified groups of risk factors should be taken into account when considering interventions.
It is recommended: (1) to document PRNP gene polymorphisms (nature, distribution and frequency) in European cervid populations; (2) to collate data to fully characterise European CWD isolates and collect data on new cases that may arise in Europe, together with NA positive control material; (3) to collect data on tissue distribution in naturally infected animals and, ideally, through experimental pathogenesis studies in cervid species; (4) and to maximise the effectiveness of the current compulsory surveillance by aiming at testing primarily animals in the risk groups and increasing sample size per primary sampling unit (PSU) (up to 30 at risk animals).
3. Assessment
3.1. Summary of the knowledge about CWD strains and their pathogenesis
Due to the incomplete understanding of the nature and molecular characteristics of prion strains, ‘strain typing’ currently relies on characterising the disease phenotype in the host, using a range of approaches including clinical presentation, histopathology and immunopathology, the biochemical properties of the PrPSc and bioassay through experimental transmission to well-established rodent models. These represent the only approaches available for the identification of prion strains, but they all have their own intrinsic limits, which impact on the final relevance of the results they provide and, on the nomenclature, used to describe the strain(s) identified within any TSE isolate.
It is beyond the scope of this opinion to exhaustively describe such methods, but more detailed reviews of these techniques can be found elsewhere (Bruce, 2003; Boyle et al., 2017) and a summary of some key points is provided in Appendix A, for ease of reference.
3.1.1. North America
Seminal transmission studies of NA CWD isolates in cervid-PrP-expressing transgenic (tg) mice (Browning et al., 2004; LaFauci et al., 2006) indicated the possibility of CWD strain variation.
Since then, there have been further transmission studies of NA CWD isolates to cervid- and noncervid-PrP expressing animals supporting the contention that several prion strains are responsible for the CWD cases observed in NA (Tamguney et al., 2006, 2009a; Johnson et al., 2011; Sigurdson et al., 2011; Crowell et al., 2015; Duque-Velasquez et al., 2015; Triscott et al., 2015; Herbst et al., 2017; Bian et al., 2019). However, due to a lack of consistency between the studies (i.e. no use of common reference isolates/strains) and differences in methodological approaches (i.e. different animal models), comparing and/or merging data from individual studies remains difficult.
Beyond these limitations, two studies originating from the same research group have provided valuable insights into the diversity of CWD strains in NA (Angers et al., 2010; Telling, 2011). The inoculation of a relatively large panel of isolates from various species and geographic locations in NA into transgenic mice overexpressing cervid PrP, indicated the presence of at least two CWD prion strains, referred to as CWD1 and CWD2, that circulate either independently or as a strain mixture. These results were consistent with transmission studies carried out using other models and CWD isolates (Tamguney et al., 2006; Di et al., 2013). Despite consistent differences in the incubation time and neuropathological profiles in cervid mice, the PrPres western blot (WB) banding patterns in the brains of mice infected by either CWD1 or CWD2 were indistinguishable from one another (Angers et al., 2010).
While the existence of at least two CWD strains in North America should be considered as an established fact, it is unlikely that the strain typing work carried out so far has provided a comprehensive or definitive picture of the diversity of CWD strains that are circulating in NA cervid populations.
CWD pathogenesis has been investigated using both naturally exposed and experimentally challenged animals and a full description of these studies can be found in a previous opinion (EFSA BIOHAZ Panel, 2017).
In summary, natural exposure apparently occurs by the oral route, through direct contact between individuals or via a contaminated environment (Moore et al., 2016a). Pathogenesis and abnormal PrP distribution in CWD are very similar to that reported in classical scrapie in small ruminants with susceptible genotypes (EFSA BIOHAZ Panel, 2014).
Following experimental challenge by the oral route, initial entry of the agent occurs through the gut-associated lymphoid tissue (GALT) with rapid involvement of the lymphoreticular system (LRS) and passage to the enteric nervous system (ENS). The CWD agent(s) then spreads to the CNS via autonomic nervous structures (Sigurdson et al., 1999, 2002; Fox et al., 2006). Early prion infectivity/ seeding activity has also been observed in the blood during the preclinical phase of the incubation period (Mathiason et al., 2006; Kramm et al., 2017).
Race et al. (2007) concluded that the involvement of the LRS seems to vary between deer and elk, with less abnormal PrP deposition in the lymphoid tissues of elk compared with deer. It is unclear at this stage whether such variations are the consequence of differences in CWD strains with differing lymphotropism and/or host PrP gene polymorphisms, or both.
A limiting factor for the understanding of the diversity of natural disease is that surveillance has not been consistently applied in NA, with some regions undertaking initial screening of lymphoid tissues only. This means that animals in which PrP accumulation is largely, or completely, limited to the CNS (as is the case for the European moose and red deer) would not be detected or investigated.
The possibility of such cases having occurred undetected is supported by the recent report of the first confirmed case of CWD in a farmed red deer in the province of Quebec in Canada in 2018, in a region where no cases of CWD had been confirmed before. The index case was a 15-month-old male, clinically healthy at slaughter. The initial enzyme-linked immunosorbent assay (ELISA) test was positive in the brain stem but negative in the lymph node, even though a low level of abnormal PrP was subsequently detected by immunohistochemistry (IHC) in a low number of follicles in the lymph node. Following the cull of the herd, over 1700 red deer were tested and an additional 10 cases of CWD were identified in females ranging in age from 18 to 28 months. All cases were positive in the obex by ELISA, IHCand WB, although the extent of abnormal PrP deposition detected by IHC was somewhat variable. A higher degree of variability in abnormal PrP accumulation was found in lymphoid tissues, with no detection by IHC in the tonsils of several cases (Walther et al., 2019). This presentation of the first outbreak of red deer in NA resembles that of a disease that is transmitted animal-to-animal, facilitated by the high density of animals, leading to high contact rates and local environmental contamination that favour horizontal transmission of disease, as opposed to the situation in wild populations.
In animals incubating CWD, abnormal PrP and/or infectivity has been demonstrated in placenta, saliva, faeces and urine which are all likely to contribute to inter-individual transmission but also to the general contamination of the environment (Mathiason et al., 2006; Tamguney et al., 2009a; Haley and Hoover, 2015; Plummer et al., 2017).
Abnormal PrP and/or prion seeding activity and/or prion infectivity has been detected in a large number of tissues (see Table 1 in EFSA BIOHAZ Panel, 2017), in particular in those commonly consumed as venison (heart, skeletal muscles, tongue, liver, kidneys) or used as dietary supplements (antler velvet) (Sigurdson et al., 2001; Angers et al., 2006, 2009; Mitchell et al., 2012). Unfortunately, in most instances, it is difficult, or not possible, to derive a quantitative estimate from the published data (Section 3.4.2) of the amount of prion/seeding activity in these tissues.
3.1.2. Europe
Due to their recent identification, the characterisation of the EU CWD cases remains incomplete. The amount of data related to the pathogenesis of the prion disease(s) identified in these animals is extremely limited as they are all field cases and most of the samples are autolysed.
In Norwegian reindeer, the presence of PrPSc in certain lymphoid organs (including in cases in which no abnormal PrP is detected in the CNS) suggests a pathogenesis similar to that of most NA cervids. However, because of the potential impact of CWD strain and/or PrP genetics on the pathogenesis of prion disease, the final distribution and level of prion infectivity in tissues of incubating and affected animals could significantly differ between EU and NA cervids. The PrPres WB patterns obtained from Norwegian reindeer were similar to those observed in an American elk CWD sample and Canadian CWD isolates including reindeer orally inoculated with NA CWD material. The immunohistochemical (IHC) distribution of PrPSc in the obex, the cerebellum and the lymph nodes was also similar to that of Canadian reindeer orally challenged with CWD (Mitchell et al., 2012; Benestad et al., 2016; Moore et al., 2016a).
Investigations carried out on three of the four positive moose cases (Alces alces) identified in Norway, for which lymphoid tissues were available, revealed the presence of detectable PrPSc in the brain but not in lymphoid tissues. Immunohistochemistry revealed that the Norwegian moose shared a common neuropathological phenotype (mainly intraneuronal staining) that clearly differed from that observed in both Norwegian reindeer and in CWD-infected NA cervids. Moreover, WB revealed a PrPres banding pattern that clearly differed from CWD cases reported so far in NA cervids and in Norwegian reindeer (Pirisinu et al., 2018). The absence of detectable abnormal PrP in the lymphoid tissues of the Norwegian, Swedish (Gavier-Widen, 2019) and Finnish moose (Korpenfelt, 2019) and the red deer (Vikøren et al., 2019), in which prion disease has been confirmed, clearly supports this contention and also suggests that in the EU, distribution patterns and level of accumulation of prions in tissues might significantly vary according to the prion strains and/or cervid species. Any extrapolation from the studies reviewed and summarised in EFSA’s Scientific Opinion (EFSA BIOHAZ Panel, 2017) to cases arising in the European context should therefore be undertaken with caution.
There are no published data related to the molecular characterisation of the Norwegian red deer isolate, but personal communication from Norway (Benestad, 2019a) indicates that this isolate has a WB pattern that is different from both the Norwegian moose and reindeer and from CWD from North America. It does have some similarities with bovine spongiform encephalopathy (BSE), but the presence of BSE has been formally ruled out as a possibility by the EURL Strain Typing Expert Group (STEG) by sPMCA methods aiming at identifying the BSE strain in an isolate (Gough et al., 2014). As for the Norwegian CWD moose, no PrPSc was detectable in the lymph nodes and tonsils of this red deer (Vikøren et al., 2019).
Another feature of the European moose and red deer CWD cases is their advanced age, all between 13 and 16 years for the moose and 16 years for the red deer, as opposed to the CWDaffected Norwegian reindeer that were aged between 1.5 and 8 years.
Transmission experiments to strain type the Norwegian CWD isolates are still ongoing, and therefore, definitive results are not yet available. Characterisation of the isolates from the four cases recently identified in elderly moose in Sweden and Finland is ongoing (see Section 3.5). The origin(s) of CWD in Europe remain unknown and while it is clear that the disease identified in the reindeer in Nordfjella is contagious, the nature of the prion disease in the other species (the European moose and red deer) remains to be established.
3.1.3. Concluding remarks
• A lack of consistency in methodologies makes comparison of data from different individual studies difficult. Although the strain typing work carried out so far has not provided comprehensive data on the CWD strains circulating in NA cervid populations, at least two CWD prion strains (CWD1 and CWD2) are responsible for disease in North America.
• The pathogenesis of NA CWD typically starts with the accumulation of abnormal PrP in the lymphoid tissues, with subsequent involvement of the CNS. The extent of involvement of the LRS seems to vary between deer and elk. However, the first NA red deer case was positive in the brainstem and negative in lymphoid tissue with the primary ELISA screening test, although low levels of PrP accumulation were subsequently detected in lymphoid tissue.
• NA surveillance has relied, in some regions, on the primary screening of lymphoid tissues only. Animals in which PrP accumulation is largely, or completely, limited to the CNS may not be detected by this method.
• Disease pathogenesis in Norwegian reindeer is similar to most NA CWD cases. However, the Norwegian moose share a common neuropathological phenotype that differs from that
observed in both Norwegian reindeer and in NA CWD cases. The Norwegian red deer isolate has a Western Blot pattern that is different from both the Norwegian moose and reindeer and from NA CWD.
• The laboratory characterisation of European cervid TSE cases remains incomplete.
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3.2.1.2. Non-cervid domestic species
The remarkably high rate of natural CWD transmission in the ongoing NA epidemics raises the question of the risk to livestock grazing on CWD-contaminated shared rangeland and subsequently developing a novel CWD-related prion disease. This issue has been investigated by transmitting CWD via experimental challenge to cattle, sheep and pigs and to tg mouse lines expressing the relevant species PrP.
For cattle challenged with CWD, PrPSc was detected in approximately 40% of intracerebrally inoculated animals (Hamir et al., 2005, 2006a, 2007). Tg mice expressing bovine PrP have also been challenged with CWD and while published studies have negative outcomes (Tamguney et al., 2009b), unpublished data provided for the purposes of this Opinion indicate that some transmission of individual isolates to bovinised mice is possible (Table 1).
In small ruminant recipients, a low rate of transmission was reported between 35 and 72 months post-infection (mpi) in ARQ/ARQ and ARQ/VRQ sheep intracerebrally challenged with mule deer CWD (Hamir et al., 2006b), while two out of two ARQ/ARQ sheep intracerebrally inoculated with elk CWD developed clinical disease after 28 mpi (Madsen-Bouterse et al., 2016). However, tg mice expressing ARQ sheep PrP were resistant (Tamguney et al., 2006) and tg mice expressing the VRQ PrP allele were poorly susceptible to clinical disease (Beringue et al., 2012; Madsen-Bouterse et al., 2016). In contrast, tg mice expressing VRQ sheep PrP challenged with CWD have resulted in highly efficient, life-long asymptomatic replication of these prions in the spleen tissue (Beringue et al., 2012).
A recent study investigated the potential for swine to serve as hosts of the CWD agent(s) by intracerebral or oral challenge of crossbred piglets (Moore et al., 2016b, 2017). Pigs sacrificed at 6 mpi, approximately the age at which pigs reach market weight, were clinically healthy and negative by diagnostic tests, although low-level CWD agent replication could be detected in the CNS by bioassay in tg cervinised mice. Among pigs that were incubated for up to 73 mpi, some gave diagnostic evidence of CWD replication in the brain between 42 and 72 mpi. Importantly, this was observed also in one orally challenged pig at 64 mpi and the presence of low-level CWD replication was confirmed by mouse bioassay. The authors of this study argued that pigs can support low-level amplification of CWD prions, although the species barrier to CWD infection is relatively high and that the detection of infectivity in orally inoculated pigs with a mouse bioassay raises the possibility that naturally exposed pigs could act as a reservoir of CWD infectivity.
3.2.1.3. Other species
Studies have demonstrated that the CWD agent(s) can be transmitted by the IC route in several species of rodents, such as voles (Subfamily Arvicolinae), deer mice (Peromyscus maniculatus), mice and hamsters (Subfamily Cricetinae). The susceptibility was, however, variable, being high in voles and deer mice but lower in mice and hamsters (Raymond et al., 2007; Heisey et al., 2010; Kurt et al., 2011; Di et al., 2013; Lee et al., 2013). Mink (subfamily Mustelinae) (Harrington et al., 2008), ferrets (Mustela putorius) (Bartz et al., 1998; Sigurdson et al., 2008) and cats (Mathiason et al., 2013) were susceptible to IC challenge with NA CWD sources, while CWD transmitted poorly to raccoons (Procyon lotor) by the IC route (Moore et al., 2019).
3.2.2. European isolates
The host range of CWD in Europe has been much less investigated so far, due to its recent identification. Among the cervid species involved in the CWD epidemics in North America, only some species (such as moose and reindeer) inhabit Europe; mule deer, white-tailed deer and elk/wapiti are American cervid species, although a few populations of white-tailed deer have been introduced into Europe. Others cervids that mainly inhabit Europe are red deer and roe deer. After the first detection in a reindeer in Norway in 2016 (Benestad et al., 2016), CWD has been detected in wild reindeer, moose and one red deer in Norway (Mysterud and Edmunds, 2019), in a moose in Finland in March 2018 and in three moose in Sweden in March, May and September 2019. CWD has not been detected so far in wild roe deer, fallow deer or white-tailed deer nor in any farmed cervid species. However, for fallow deer and white-tailed deer, the number of animals tested by the surveillance systems is still very low.
The potential host range of European CWD strains is under investigation by bioassay experiments in a range of model species; most of these studies are ongoing and there are no published data available so far. Data from the experiments that are known to be ongoing in different laboratories have been gathered for the purposes of this Opinion. Overall, reindeer CWD, moose CWD and red deer CWD brain isolates (and LRS isolates from some selected cases) are being tested for transmissibility in mice, hamsters, bank voles and in a range of tg mouse lines expressing PrP sequences from: cervids (Q226 or E226 deer PrP variants), small ruminants (ARQ, VRQ, AHQ and ARR PrP polymorphic variants), cattle, pig, vulture and human (M129 and V129 PrP polymorphic variants) (see Section 3.3.1). Importantly, in most of these animal models, the transmissibility of European CWD isolates will be directly comparable with the outcome of similar (published or ongoing) experiments with CWD isolates from North America.
While most of these studies are still ongoing, some experiments with CWD isolates from Europe have already produced evidence of transmission in some recipient species (Table 1). These include bank voles, conventional laboratory mice and tg mice expressing cervid PrP, sheep PrP and mouse PrP. The same rodent models are also susceptible to NA CWD isolates and will therefore allow comparative strain typing of NA and European CWD strains in due course. There is no strong evidence so far for rodent models being widely susceptible to NA isolates but not to European isolates or vice versa.
Table 1 summarises more than 500 ongoing, published or unpublished primary transmission experiments of NA or European CWD isolates from different cervids into various rodent models, which have been gathered following the requests described in Section 2.2. The CWD isolates are grouped according to geographical origin and cervid species, with each column summarising the results obtained with one or more CWD isolates from a given species and country. Rodent models are grouped according to the PrP species expressed. Some species have polymorphic PrP sequences, so more than one PrP sequence per species has been modelled. In these cases, each row summarises the data obtained with more than one PrP variant of a given species. Therefore, conventional mice include wt mice expressing PRNPa or PRNPb mouse PrP variants; bank voles include two genetic lines with different amino acids at codon 109 (Bv109M and Bv109I); tg-cervidPrP mice include mouse lines expressing several cervid PrP variants (the deer wt Q226, the elk wt E226, the WTD variant S96, the elk variant M132); tg-sheepPrP mice include mouse lines expressing the ARQ, VRQ, AHQ or ARR small ruminant PrP variants; finally, tg-humanPrP mice include mouse lines expressing M or V at the human PrP polymorphic codon 129. Therefore, each box in the Table 1 summarises the outcome of bioassay experiments with one or more CWD isolates (from the same species and origin) in one or more recipient rodent models (expressing PrP from a single given species).
Table 1: Summary of the state of research on experimental transmission models of CWD isolates in North America and Europe
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Most of the studies conducted by molecular/biochemical methods are still ongoing. The preliminary data obtained by molecular/biochemical methods were difficult to summarise and will not be reported in the present Opinion. This was mainly due to lack of detail in the results obtained by direct PrPSc analyses (PrPres typing, conformational stability, proteinase K resistance, which are intended to investigate CWD strains) and to the different methodological approaches employed in amplification assays (PMCA and RT-QuIC). The information gathered by this activity shows that experiments aimed at modelling the species barrier for NA or European CWD isolates into different animal species, including humans, are underway in different laboratories and will be of help for understanding the potential host range of CWD strains.
3.2.3 Impact of the PRNP gene on transmissibility
Polymorphisms in the PRNP gene are known to influence susceptibility/resistance to prion disease in both small ruminants and humans (for recent review, see EFSA BIOHAZ Panel 2014, EFSA BIOHAZ Panel, 2017; Diack et al., 2014). Effects of host PRNP polymorphisms on CWD susceptibility/resistance have also been described in a number of cervid species (reviewed in EFSA BIOHAZ Panel, 2017, 2018). However, deer and elk wild-type PrP primary structures are equivalent, except at residue 226, which is glutamate in elk and glutamine in deer. The effect of this difference on CWD pathogenesis has been recently investigated using a gene-targeting approach in which the mouse PrP coding sequence was replaced with elk or deer PrP. The results obtained following experimental challenge with deer and elk CWD inocula from NA showed that the resulting GtE226 and GtQ226 mice had distinct kinetics of disease onset, with incubation times shorter in GtE226 than in GtQ226 mice, indicating that amino acid differences at PrP residue 226 dictate the selection and propagation of divergent strains in deer and elk with CWD. As prion strain properties largely dictate host range potential, these findings suggest that prion strains from elk and deer might pose distinct risks to sympatric species or humans exposed to CWD (Bian et al., 2019).
The most common cervid species in Europe (moose, red deer, reindeer and roe deer) share the same PrP primary structure, i.e. Q226. However, red deer PrP is polymorphic at residue 226 and can therefore code for either Q226 or E226. Interestingly, CWD cases detected so far in four Norwegian moose, the first Swedish moose and one Norwegian reindeer are all homozygous for Q226 (Benestad, 2019b,c,d), but the CWD case in red deer is instead homozygous for E226 (Vikøren et al., 2019). The impact of these differences in PrP genotype on the transmissibility and strain properties of European CWD isolates is currently under investigation using GtE226 and GtQ226 mice (Bian et al., 2019). PRNP genotypes of the other reindeer from Norway and of the other moose cases in Sweden and Finland are not in the public domain.
Data on the transmissibility of CWD in species with different PrP sequences obtained by in vivo or in vitro modelling allow the investigation of the structural basis of the transmission barriers for CWD. This in turn could provide hints for predicting, to some extent, the susceptibility of non-cervid species to CWD. Taken together, studies with CWD isolates from NA suggest that the 165–175 sequence similarity between cervid and host PrP is one important factor governing the susceptibility of different species to CWD (reviewed by Kurt et al., 2016). In particular, polymorphisms at N/S170 in the recipient species might be important for susceptibility, with species that have N170 being more susceptible than those with S170 (Kurt et al., 2016). However, this must not be seen as an absolute rule, as species having S170 in their PrP, such as squirrel monkeys, have also been reported to be susceptible to CWD. It is however pertinent to note that all livestock species and humans have PrP sequences with S170, so they should not be considered among the species with supposedly high susceptibility to NA CWD isolates. Ongoing experiments in rodent models seem to indicate a similar trend for European CWD isolates, as rodent models, apparently more susceptible to European CWD isolates such as bank voles and tg mice expressing deer PrP, are N170.
Little information is currently known about the genetics of either wild or farmed cervid populations in Europe. A recent published study of several deer species (mostly in Great Britain) reported that red deer showed the most PRNP gene variation, with polymorphisms at codons 98, 168, 226 and 247 and marked variability in genotype frequencies in different regions. Other deer species showed less variation, with roe and fallow deer having identical PRNP gene sequences in all the animals sampled. Based on comparison with PRNP sequences of NA cervids affected by CWD and limited experimental challenge data, the authors conclude that a high proportion of wild deer in Great Britain may be susceptible to CWD (Robinson et al., 2019). A similar conclusion was reached by a previous study of 715 genotyped cervids (red deer, roe deer and chamois) from the UK and Italy (Peletto et al., 2009).
3.2.4. Concluding remarks
• The transmission of prions between species is limited by the ‘transmission barrier’ and the amino acid sequence of the host PrP plays a very key role in the overall susceptibility to TSE. Even for prions deriving from the same species, the host range may vary according to the prion strain, implying that different CWD strains might have different host ranges and different potential for transmitting to livestock species and to humans.
• Whether the natural host range of CWD in NA extends beyond the family Cervidae is currently unclear and no natural infections have been reported so far in other wildlife species (e.g. predators and scavengers) with overlapping geographical ranges.
• NA CWD has been transmitted experimentally to cattle and sheep, but with incomplete attack rates. The species barrier appears higher for pigs, although challenged animals can support low-level prion amplification.
• Experimental transmission to tg mice and other rodent models shows some difference in the host ranges of different isolates but, particularly for the European isolates, many bioassays are still ongoing and data are not yet available.
• The number of strains, the strain diversity, the prevalence and the potential host range of disease in both NA and Europe CWD may be underestimated.
3.3. Transmissibility to humans: the zoonotic potential
The zoonotic potential of CWD has been addressed by several research groups through in vitro and in vivo approaches. However, it must be underlined that, at the time of writing this Opinion, the corresponding publications report results only based on CWD isolates derived from naturally or experimentally infected cervids from NA and none with isolates from Europe.
3.3.1. In vitro conversion of human PrP
Several approaches developed for converting PrP in vitro have been proposed to model the species barrier (EFSA BIOHAZ Panel, 2015). These techniques are based on the ability of infected samples (here derived from animals) to convert normal (here human) PrP (PrPc ) in vitro under different experimental conditions. For these studies, the PrP substrate submitted to conversion can be either recombinant PrP or a brain homogenate. The latter source not only has the advantage of being able to present the natural diversity of PrP isoforms, but other components (e.g. nucleic acids, proteins, lipids) are also present with their potential influence on the reactions of conversion (e.g. co-factors, inhibitors).
The conversion of human recombinant PrPc (recPrPc ) triggered by NA CWD isolates is very limited, if any, in comparison with the conversion induced by other prion sources reputed to be efficiently infectious for humans. Therefore, in the presence of sodium dodecyl sulfate (SDS), human recPrPc was efficiently seeded by sporadic Creutzfeldt–Jakob disease (sCJD) or BSE purified infectious samples, but not by scrapie or white-tailed deer CWD samples (Luers et al., 2013). Conversely, the RT-QuiC technique of PrP amplification was efficient with eight different isolates derived from CWD-infected white-tailed deer, compared with BSE, which fails to convert human recPrP with this technique (Davenport et al., 2015). In the presence of guanidine, elk and mule deer PrPSc are able to induce a limited conversion of methionine homozygous at codon 129 (MM) human recPrPc (these CWD seed sources converted homologous cervid recPrPc with a 15-fold higher conversion rate) but did not convert valine homozygous at codon 129 (VV) human recPrPc (Raymond et al., 2000). Similar levels of conversion of human recPrPc were obtained with scrapie-infected ovine PrPSc, whereas BSE-infected bovine PrPSc was slightly more efficient at converting human recPrPc (conversion rate ninefold less efficient than with homologous PrPc ).
The conversion of human PrPc by CWD seeds was more efficient when normal brain homogenates were used as the source of normal PrP. Amplification studies based on the PMCA technique have demonstrated that the efficiency of in vitro conversion of human PrP is highly influenced by the PrP polymorphisms of the human recipient, PrP polymorphisms of the cervid donor and the origin of the isolates (Barria et al., 2018). In cervids, the polymorphism at codon 132 (methionine or leucine) plays an important role in CWD susceptibility (Hamir et al., 2006c), as does the polymorphism at codon 129 (methionine or valine) for humans with regard to susceptibility to CJD. With elk CWD samples, ‘only the homologues methionine homozygous seed-substrate reactions could readily convert the human PrP’ (132 MM elk sample on 129 MM human PrP) whereas other combinations were less efficient (Barria et al., 2018). However, the rate of conversion of human PrPc by elk CWD samples remains lower than the conversion observed with BSE samples, but higher than the conversion induced by L-BSE, H-BSE or scrapie (Barria et al., 2014). Also, efficient PMCA conversion and amplification of human PrPc of the three human genotypes (MM, MV and VV) were observed with infectious materials derived from two reindeer experimentally infected with CWD (Barria et al., 2018). Conversely, PMCA amplification was very limited with white-tailed deer (Barria et al., 2018) and mule deer CWD samples (Barria et al., 2011). In the latter, the species barrier was broken through serial amplifications of mule deer CWD on a homologous substrate, suggesting that, after serial intraspecific passages, the zoonotic potential of CWD (if any) might increase. Other parameters (like the low pH of the lumen of the stomach) might influence susceptibility to CWD (Li et al., 2007): the rate of conversion of human PrPc by CWD-infected elk brain in the presence of guanidine is highly enhanced (reaching similar levels of conversion to those obtained for cervid PrP) in acidic conditions but not in neutral conditions. Table 2 describes the main in vitro studies exploring the zoonotic potential of CWD by assessing the conversion of human PrP in the presence of CWD seeding material.
Table 2: Summary of the in vitro studies aimed at exploring the human species barrier to CWD
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Taken together, these in vitro studies suggest that, within the limits of the ruminant isolates that were used in them,
• BSE (established zoonotic potential) presents the highest ability to convert human PrP;
• CWD isolates derived from (132 MM) elk and experimentally challenged reindeer would present an intermediate potential for conversion of human PrP;
• other sources would be less efficient at converting human PrP. This includes CWD isolates derived from deer, atypical H-BSE and L-BSE strains or scrapie isolates, even if the zoonotic potential of atypical BSE and scrapie is supported by experimental evidence of transmission in tg humanised mice (Beringue et al., 2008a; Cassard et al., 2014) and non-human primates (Gajdusek, 1972; Gibbs and Gajdusek, 1973; Comoy et al., 2008, 2015; Ono et al., 2011).
3.3.2. In vivo studies of zoonotic potential of CWD isolates
Transgenic mice expressing human PrP and non-human primates are the two classes of in vivo experimental models used to evaluate the zoonotic risk of animal prions for humans.
3.3.2.1. Transgenic humanised mouse models
Several tg humanised mice lineages based on key polymorphisms at codon 129 of the human PRNP gene (six lineages of MM, one lineage of MV and two lineages of VV) expressing onefold to 16-fold the physiological levels of PrPc have been exposed to NA CWD isolates derived from elk, mule deer or white-tailed deer in the context of six independent experiments. No clinical, histopathological or biochemical evidence of neurological prion disease has been observed in any of these mice, even after extended incubation periods. According to these results, there is a high transmission barrier to humans for CWD. Nevertheless, this conclusion should be modulated by the fact that no blind secondary miceto-mice transmission was performed in any of these studies. Indeed, this approach in tg humanised mice resulted in the conclusion that some zoonotic potential for scrapie could not be ruled out (Cassard et al., 2014).
Table 3 describes the main in vivo studies exploring the transmissibility of CWD to humanised transgenic models and non-human primate species as proxies for the zoonotic potential of CWD.
Table 3: Summary of the in vivo studies exploring the transmissibility of CWD to humanised transgenic models and non-human primate species
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Nevertheless, Race et al. (2019) recently published a study performed with two lineages of humanised mice that provided intriguing results. They exposed tgRM and tg66 mice, which overexpress MM human PrP at levels two- to fourfold and 8- to 16-fold higher than the physiological levels, respectively, to different CWD sources. These two models harbour the highest levels of PrPc expression among all those that have been tested in these studies. Among these mice, 7% (3/45) tgRM and 30% (15/52) tg66 mice fitted the ‘criteria as prion disease suspects’ that the authors considered to be relevant and that correspond to ‘signs of wasting, weakness, neurologic disease and behavioural changes’ (Race et al., 2019). Extensive analyses of the brains of these animals did not provide any lesional, biochemical or immunohistochemical element that could confirm the diagnosis of prion disease and the authors expressed some reservations about the relevance of those observations because of the advanced age of these animals (> 500 days of incubation). In parallel, the authors analysed the brains of all the inoculated animals using RT-QuIC. Four tg66 mice exposed to CWD samples were identified with repeated positive reactions (nine other exposed animals showed initial, positive reactions that were not reproducible). The authors wonder whether ‘the seeding activity detected in these mice may represent a low level of CWD agent, suggesting a possible transfer of CWD infection’, or ‘these results might be due to false-positive reactions or residual CWD inoculum’. Unfortunately, the authors did not indicate whether the animals that exhibited a positive RT-QuIC reaction were those that were clinically suspect.
It must be noted that the authors did not test the spleens of these animals. Indeed, during Prion 2015 (Fort Collins) and Prion 2019 (Edmonton) conferences, Kong et al. reported in oral presentations the partial transmission at subclinical levels of CWD to humanised mice (different transgenic constructions), with splenic involvement (Comoy et al., 2019a). This situation is reminiscent of observations made in humanised mice exposed to variant Creutzfeldt-Jakob disease (vCJD) prion strain (Beringue et al., 2008b). In a similar way, the study of Race et al. (2018) missed the analysis of the spinal cords of these CWD-exposed humanised mice. Indeed, unexpected disease phenotypes selectively affecting spinal cord without brain involvement have been observed in mice and macaques under non-optimal conditions of experimental transmission (Comoy et al., 2017).
3.3.2.2. Chimeric mouse models
Humanised mice that were highly susceptible to CWD were obtained by modifying four amino acids (positions 166, 168, 170 and 174) in red in Table 4 at the level of the a2–b2 loop of the human PrP to perfectly match that of the elk PrP (Kurt et al., 2015). These observations suggest that this part of the prion protein constitutes a substantial structural barrier for CWD transmission to humans. The influence of this protein loop on species barrier might be different for BSE (transmissible to humans) and scrapie (zoonotic potential under question), as cattle and ovine PrP share the same amino acid sequence at the level of the a2–b2 loop that only differ for amino acids 166 and 168 from the human PrP sequence.
Table 4: Comparison of the wild-type PrP sequences of different species (only differences from the sequence of elk PrP are shown) (Schatzl et al., 1995; Li et al., 2007; Kurt et al., 2015). The reference numbers of equivalent amino acids positions (AA) differ among species due to a difference of octapeptides numbers and/or insertion/deletion of AA at the N-terminal part of the PrP. The letters refer to the standard designation for amino acids and the box denotes the section of the PrP corresponding to the a2–b2 loop
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The experiments performed in non-human primate (NHP) models modulate the influence of this a2-b2 loop on the species barrier towards CWD. Squirrel monkeys (subfamily Saimirinae) and CM (Macaca fascicularis) exhibit different susceptibilities to CWD (Race et al., 2009, 2014), whereas they harbour the same amino acids in the a2–b2 loop (i.e. they differ from human at positions 166 and 168 and from cervids at positions 170 and 174).
3.3.2.3. Non-human primate models
In New World NHP squirrel monkeys, CWD from both MD and elk-derived isolates is transmissible through the IC route with incubation periods similar to those obtained with BSE (Marsh et al., 2005; Williams et al., 2007; Race et al., 2009; Piccardo et al., 2012) suggesting a similar susceptibility of squirrel monkeys to these two animal prions. CWD isolates derived from WTD also transmitted disease, but with longer incubation periods despite a higher infectious titre in the inocula. All these cervid isolates also transmitted CWD to squirrel monkeys after exposure through the oral route (Table 5). After secondary transmission, the incubation periods for CWD decreased (Race et al., 2014): all the features of a classical prion disease, namely specific lesions and accumulation of abnormal PrP, reproducible lesional profile and adaptation of the prion strain to the new host, are found in squirrel monkeys after exposure to CWD.
The situation in CM is very different. After intracerebral (six animals) and oral exposure (eight animals) to the same inoculum as those that have transmitted CWD to squirrel monkeys, no clinical, lesional or biochemical evidence of prion disease was identified in macaque recipients (Race et al., 2009, 2014, 2018) and extensive RT-QuIC analyses of their brain did not provide any evidence of seeding. However, it must be underlined that the incubation periods of macaques after primary exposure to animal prions strains through the intracerebral route are classically extended, with BSE developing up to 93 mpi (~ 8 years) and scrapie proving transmissible 118 mpi (~ 10 years) (Comoy et al., 2015). In this study performed at the Rocky Mountain Laboratories (RML) (USA), it can therefore be concluded that four of the six IC-inoculated macaques have been kept under surveillance for too short a period (less than 95 months) to draw any definitive conclusion (Table 6).
Another study (Canadian), described in the background of this mandate and based on exposure of CM to CWD, is still in progress and not yet published. However, intriguing/interim observations have been the subject of several oral presentations. Eighteen 4-year-old female macaques were exposed through intracerebral, oral, intravenous routes and skin scarification to different isolates derived from CWD-infected animals (MD, WTD and elk sources, experimentally or naturally exposed, from USA and Canadian origins). Among these animals, 10 animals were subjected to intense/extensive diagnostic testing. Animals were sacrificed, or died from unrelated causes, less than 90 months after exposure (two animals IC exposed to elk CWD, four animals IC exposed to CWD-infected WTD, one animal orally exposed to brain samples derived from CWD-infected WTD and three animals exposed to muscles derived from CWD-infected WTD and MD). Among these, four (54–81 months of incubation) exhibited behavioural/neurological changes and/or alterations of the general status including anxiety, apathy, ataxia, tremor and wasting. Three of them were diagnosed as diabetic via elevated blood glucose and glycated haemoglobin (HbA1c) levels. It is notable that in the previously mentioned RML study (Race et al., 2018), nine of the 14 macaques were euthanised because they exhibited similar signs associated with neurological manifestations (aggression, seizure or tremor) or metabolic problems (anorexia, wasting, four diabetes cases). Spontaneous diabetes is described in the CM, but it
Table 5: Incubation periods of infected squirrel monkeys after exposure to different prion isolates through the intracerebral route
The situation in CM is very different. After intracerebral (six animals) and oral exposure (eight animals) to the same inoculum as those that have transmitted CWD to squirrel monkeys, no clinical, lesional or biochemical evidence of prion disease was identified in macaque recipients (Race et al., 2009, 2014, 2018) and extensive RT-QuIC analyses of their brain did not provide any evidence of seeding. However, it must be underlined that the incubation periods of macaques after primary exposure to animal prions strains through the intracerebral route are classically extended, with BSE developing up to 93 mpi (~ 8 years) and scrapie proving transmissible 118 mpi (~ 10 years) (Comoy et al., 2015). In this study performed at the Rocky Mountain Laboratories (RML) (USA), it can therefore be concluded that four of the six IC-inoculated macaques have been kept under surveillance for too short a period (less than 95 months) to draw any definitive conclusion (Table 6).
Another study (Canadian), described in the background of this mandate and based on exposure of CM to CWD, is still in progress and not yet published. However, intriguing/interim observations have been the subject of several oral presentations. Eighteen 4-year-old female macaques were exposed through intracerebral, oral, intravenous routes and skin scarification to different isolates derived from CWD-infected animals (MD, WTD and elk sources, experimentally or naturally exposed, from USA and Canadian origins). Among these animals, 10 animals were subjected to intense/extensive diagnostic testing. Animals were sacrificed, or died from unrelated causes, less than 90 months after exposure (two animals IC exposed to elk CWD, four animals IC exposed to CWD-infected WTD, one animal orally exposed to brain samples derived from CWD-infected WTD and three animals exposed to muscles derived from CWD-infected WTD and MD). Among these, four (54–81 months of incubation) exhibited behavioural/neurological changes and/or alterations of the general status including anxiety, apathy, ataxia, tremor and wasting. Three of them were diagnosed as diabetic via elevated blood glucose and glycated haemoglobin (HbA1c) levels. It is notable that in the previously mentioned RML study (Race et al., 2018), nine of the 14 macaques were euthanised because they exhibited similar signs associated with neurological manifestations (aggression, seizure or tremor) or metabolic problems (anorexia, wasting, four diabetes cases). Spontaneous diabetes is described in the CM, but it classically occurs in 1–2% of captive monkeys (Clarkson et al., 1985), often in obese animals that represent less than 20% of the general population (Bauer et al., 2010). A correlation between the onset of obesity and diabetes and the infection with prions (BSE in their case) has been described by other authors (Strom et al., 2014).
The animals included in the Canadian study were tested for the presence of specific hallmarks of prion disease. Throughout oral presentations in congresses and personal communications with WG members, the authors mentioned that they observed an increased PrP staining evidenced by IHC in the substantia gelatinosa of suspected animals (i.e. the upper part of the posterior horns of their spinal cord) and brain areas (Comoy et al., 2019b). They consider that this labelling is reminiscent of what has been observed and described in primates orally challenged with BSE and that did not develop classical BSE but lesions and atypical PrP accumulation confined to the lumbar cord (Holznagel et al., 2013). However, this labelling is considered by several authors to be physiological as it was observed in the spinal cords of control animals in the RML study (Race et al., 2018) and has been observed in the spinal cord of normal animals of other species (Simmons et al., 2011).
Moreover, the authors of the Canadian study reported that abnormal PrPres in WB and positive RT-QuiC reactions were obtained with lumbar cord samples from some suspected macaques.
These two studies provide apparently contradictory results that may be explained by several factors. Indeed, the RML study exposed older individuals (mean 7.2 years, range 5.2–11.4 years except two animals that were 3–4 years old), in contrast to the Canadian study where animals were 4 years old at exposure, as it is customary. Moreover, the sources of inocula were different, and the animals were challenged with larger amounts of inocula in the Canadian study (10 mg vs 5 mg for IC route, 10 g vs 1 g for oral route, oral dosing with 5 kg of muscle per animal in the Canadian study). Definitive conclusions and publication of these studies are now required in order to have more detailed information and more accurate comparisons, including bioassay results in tg mice and bank voles.
It can be concluded from these two studies that after incubation periods of between 5 and 13 years, no classical prion disease with neurological manifestations, spongiform changes and accumulation of abnormal PrP is seen in CM following challenge with CWD. However, it must be remembered that under non-optimal conditions of exposure, two independent studies have reported that BSE/vCJD infection in macaques and mice might lead to the expression of an atypical disease that does not fit the current criteria of prion diseases (Holznagel et al., 2013; Comoy et al., 2017). The observations provided by both the RML and Canadian studies raise the possibility of a similar situation after exposure of primates to CWD.
Table 6: Duration of surveillance periods of cynomolgus macaques exposed to different prion isolates
3.3.3. Concluding remarks
• CWD isolates from NA have shown variable ability to convert human PrP in in vitro studies. In vivo studies have also produced contradictory results, precluding any definitive conclusion about the ability of CWD to cross the human species barrier.
• Extrapolation from the NA situation with regard to zoonotic potential might lead to either an underestimation or an overestimation of the zoonotic potential of the already identified European isolates, which have been shown to be distinct from NA CWD and from each other, based on the biochemical and biological characteristics that have been defined to date.
3.4. The risk to humans from CWD
As described in the EFSA Scientific Opinion on the review of a scientific publication on the zoonotic potential of ovine scrapie prions (EFSA BIOHAZ Panel, 2015), the link between human and animal TSE cases can be addressed ‘directly by conducting molecular/biological comparison to determine the biological and biochemical similarities of TSE isolates from two different species. It can also be addressed through epidemiological studies that could set hypotheses for putative risk factors via descriptive observational studies or via analytical studies aimed at detecting significant associations between exposure (risk factors) and outcome (health event of interest)’.
Previous sections summarise the biological and biochemical characteristics of the different CWD isolates in Europe and NA. There is a lack of knowledge about the ability of the CWD agent(s) to cross the species barrier and to infect humans. No data are available either on other factors that could determine the uptake of the infectious agent by a new host (humans), such as the amount of agent present, the age of the host at exposure and the possible potentiating effects of intercurrent disease or injury of the host. These and many other factors have been speculated to affect the success of infection following exposure, but the precise roles and interdependence (if any) of these factors are not clear. It is therefore not possible to perform a risk assessment of CWD in humans.
3.4.1. Epidemiological studies
The caveats associated with using epidemiological studies to investigate the association between human and animals TSE have all been previously highlighted (EFSA BIOHAZ Panel, 2015). These include the reliability of disease occurrence estimates from surveillance data and the inability to control for the effects of potential confounding factors, such as CWD diversity, host genetics, lag time (potential incubation period of human TSE), ecological fallacy and exposure misclassification.
A systematic review of the current evidence on the transmissibility of CWD prions to humans has been published recently (Waddell et al., 2018), using the criteria set-up through the Grading of Recommendations Assessment, Development and Evaluation (GRADE) (Schunemann et al., 2013). € Three types of studies were assessed: epidemiological studies, in vitro and in vivo experiments. The GRADE of the quality of evidence for the five epidemiological studies assessed suggested that future evidence may be inconsistent with the conclusions of the currently available studies. For the two studies on macaques (see Section 3.3.2), GRADE indicated that there is limited confidence that the results and estimates presented will not change with future research (mainly due to the limited number of studies and observations available). GRADE of the seven studies on humanised transgenic mice, which provided no evidence to support the possibility of transmission of CWD prions to humans, indicated that there is some confidence the overall conclusions of this research will not change with future research. The authors concluded that ‘future discovery of CWD transmission to humans cannot be entirely ruled out on the basis of current studies, particularly in the light of possible decades-long incubation periods for CWD prions in humans and recommended to exercise caution when handling potentially contaminated material and explore CWD management opportunities’.
Among the more recent studies not included in the systematic review by Waddell et al. (2018), Abrams et al. (2018) have investigated the rates of human prion disease in States of the USA with and without CWD, to examine the possibility of undetermined zoonotic transmission. Although final results of this study have not been published yet, the authors concluded that ‘while higher prion disease mortality rates in certain categories of states with CWD in free-ranging cervids were noted, additional stratified analyses did not reveal markedly elevated rates for potentially sensitive subgroups that would be suggestive of zoonotic transmission. Unknown confounding factors or other biases may explain state- by-state differences in prion disease mortality’.
Maddox et al. (2019) conducted a retrospective cohort study of 1,546 residents in 15 counties of the State of Wisconsin in which CWD has been confirmed among harvested free-ranging deer. By linking three databases, the study aimed to evaluate causes of mortality in individuals potentially exposed to CWD. The results of the study have not been published yet but preliminary results identified individuals that consumed CWD-positive deer but with no matches in the National Prion Disease Pathology Surveillance Center (NPDPSC) neuropathology database. Due to the long incubation period, should transmission to humans occur, many years of vital status tracking are needed.
The potential variability of phenotypes of prion disease in humans and the potential for association with a zoonotic strain of CWD is an increasing area of concern in CWD-endemic regions given the impossibility of knowing what the phenotype of human CWD prions would present with or whether they would be distinct from sporadic CJD cases. One example of a study looking at this aspect is the current analysis of the molecular diversity of CJD cases in patients who resided in Alberta and Saskatchewan (Canada) at their time of death (Myskiw et al., 2019). In a similar study, frozen brain tissues from all available sCJD cases archived in the NPDPSC from a US State with a high incidence of CWD are being analysed, looking for unusual patterns, characteristics and/or distribution of PrPSc in comparison with sCJD samples from States that have not detected CWD (Liu et al. (2019)).
3.4.2. Exposure assessment
There are two distinct routes of potential exposure of humans to the CWD agent(s):
1) Handling and manipulation by professionals (including industrial workers), hunters, consumers, etc., of dead bodies, carcasses, meat cuts, animal by-products including risk material and meat, meat products and offal infected with the CWD agent(s).
2) Consumption of meat, meat products and offal from animals infected with the CWD agent(s). The assessment of CWD risk to humans, generically defined as the probability of transmission to humans through the handling and/or consumption of meat and meat products from cervids is currently impossible, but could hypothetically be defined at two levels:
1) At the individual level, as the probability that at least one human is exposed to the CWD agent, acquiring the infection and developing either a known, an emergent or a new TSE.
2) At the population level, as the number of new human TSE cases in a defined population (incidence).
Considering each of these routes in turn, there is no evidence of anyone having acquired a human prion disease by handling and butchering infected animals of any species. However, the exposure of humans via direct contact (wounds, skin lacerations) while handling this type of material cannot be ruled out. Exposure to infected meat at household level may occur when consumers handle purchased raw meat, meat products or offal or, for home-slaughtered or hunted cervids when carcasses are butchered and dressed. The frequency of exposure through handling of fresh meat, meat products or offal will be different between professionals and consumers. However, ToR3 only requires the consideration of the risk of transmission to humans through the consumption of cervid meat and meat products.
The most likely source of exposure and the only one considered in this Scientific Opinion, is through the consumption of cervid meat, meat products and offal sourced from infected animals. Two events must occur for a human to be exposed: the animal must be infected with a TSE in which abnormal PrP/infection is present in edible peripheral tissues, mainly the musculoskeletal (including blood) and lymphatic systems and the consumer must have access to meat, meat products or offal from such animals in which the abnormal prion has not been inactivated by physicochemical or any other processing.
There are no studies in the scientific literature aimed to derive the amount of CWD infectivity potentially present in different tissues of susceptible species. Several studies describe the presence/ absence of detectable PrP in a range of tissues (see table 1 in EFSA BIOHAZ Panel, 2017). A single study (Gavin et al., 2019) has attempted to estimate, via mathematical modelling, the titre of infectivity that would pass, through abattoir killed or field dressed deer, into the human food chain and the environment. This study assumed that infectivity in red deer infected with CWD would be peripherally distributed and with a pathogenesis similar to classical scrapie. The model estimated that the total infectivity in a red deer carcass would be approximately 83,000 mouse IC log ID50 units, compared with around 22,000 in a scrapie-infected sheep carcass, mainly due to the size difference between sheep and red deer. The model estimated that around 13% (11,000 mouse IC log ID50 units) of the total infectivity would enter the food chain through either the farmed or wild route.
For the probability of exposure to the CWD agent(s):
• At the individual level, consumers of meat, meat products and offal derived from CWD-infected cervids will be exposed to the CWD agent(s) and, to a lesser extent, via the handling of infected material with strain(s) causing peripheral tissue distribution of infectivity in CWDinfected cervids. As stated in a previous EFSA Opinion on CWD (EFSA BIOHAZ Panel, 2018), even if specific tissues harbouring most of the infectivity were removed from the food chain, therefore reducing the human dietary exposure to infectivity, consumers would still be exposed to the CWD agent(s) via consumption of meat and meat products.
• At the population level, not only it is important to consider the strain(s) of agent in susceptible cervid species that are usually consumed (reindeer, moose, red deer), but also the prevalence of each CWD strain in each of these species. This would provide an overall estimation of the probability of exposure of EU citizens to the CWD agents/strains. However, there is no conclusive knowledge about the range of agents/strains of CWD in the European cervid population, their tissue distribution in infected animals or their prevalence in each/any of the populations. Therefore, the overall exposure of humans to CWD in the EU cannot be estimated.
3.4.3. Recommendations on possible additional control measures to address the risks identified
Recommendations that would reduce/eliminate human exposure to CWD all relate to the reduction or removal of infected tissues from the food chain by:
• Systematic testing: Only allowing human consumption of meat, meat products and offal sourced from animals that have been tested negative for CWD.
• Targeted measures: Prohibition of harvesting/hunting susceptible species or the introduction of compulsory testing of animals before human consumption in/from declared infected premises/ areas (e.g. a farm, or a surveillance PSU (Section 3.6), region, country, etc.).
• Systematic removal of high-risk tissues from all cervids intended for human consumption with no requirement for testing.
3.4.4. Concluding remarks
• Due to uncertainties and lack of data, it is not possible to conduct a risk assessment of CWD in humans and to directly quantify the human risk at either individual or population levels. The risk to humans through consumption of meat, meat products and offal derived from CWDinfected cervids cannot be directly assessed; only the probability of exposure to the CWD agent(s).
• Lack of comprehensive data on both the tissue distribution of infectivity in European cases and the prevalence of the CWD gent in each of the species, increases the uncertainty around human exposure and related risk factors.
• The available epidemiological studies have not shown any evidence of association between human TSE and NA CWD. However, these studies suffer from many methodological and logistic constraints.
• A recent systematic review concluded that the long incubation periods in human TSE mean that current studies do not definitely exclude any potential for CWD to transmit to humans.
• Even if the specific tissues harbouring most of the infectivity were removed from the food chain, therefore reducing the human dietary exposure to infectivity, consumers would still be exposed to the CWD agent(s) via consumption of meat and meat products from infected animals.
• Exclusion from the food chain of the whole carcass of any infected animal would be required to eliminate human dietary exposure. This could be facilitated by the preliminary testing of animals intended for consumption and/or the prohibition of harvesting or hunting susceptible species in infected premises/areas.
3.5. Situation of CWD in Europe: latest results
In 2018, Norway ‘embarked in an unprecedented eradication campaign of CWD in Nordfjella area where all the cases of CWD in reindeer have been found so far. As a result, between 10 August 2017 and 14 May 2018, 582 reindeer were culled during the normal hunting seasons, 1,399 reindeer were shot dead by professional marksmen. An additional 43 reindeer were found dead due to natural causes, making the total of the wild reindeer population removed by the eradication programme 2,024 wild reindeer’ (Mysterud and Rolandsen, 2018).
A recent study analysing the data of the Nordfjella area estimated the apparent CWD prevalence at 1.2% of adults in the infected population of wild reindeer, while the estimated true prevalence was 1.6% (Viljugrein et al., 2019).
The results of the surveillance conducted in cervids for TSE in the European countries have been summarised in the Tables 7 and 8. Before 2018, European countries had tested cervid populations for TSE in a very heterogeneous and inconsistent way (for a review of the EU surveillance before 2016 see EFSA BIOHAZ Panel, 2017, 2018), with Romania accounting for more than 90% of all cervids tested in the EU in the last 3 years.
Following the confirmation of the first case of CWD in Europe, the European Commission through Annex III of Regulation (EC) No. 999/2001, amended by Commission Regulation (EU) 2017/1972, enforced the implementation of a 3-year monitoring programme for CWD from 1 January 2018 to 31 December 2020 in the six MS that have a wild and/or farmed and/or semi-domesticated population of moose and/or reindeer: Estonia, Finland, Latvia, Lithuania, Poland and Sweden.
The programme requires the identification of geographically based PSU, which shall cover all territories in which cervid populations are present, for farmed and captive cervids and for wild and semi-domesticated cervids. The sampling strategy is two-stage: sample all PSU if the identified PSU list contains less than 100, or a random sample of 100 PSU if the identified PSU list contains more than 100. Within each selected PSU, a target sample of 30 risk animals is required.7 If an MS identifies fewer than 3,000 risk animals either among wild/semi-domesticated or farmed/captive cervids, it may extend the monitoring to hunted or slaughtered cervids declared fit for human consumption with the objective of approaching a total number of 3,000 wild and semi-domesticated cervids tested at the national level over the 3-year period that is relevant to it.
According to the Regulation, the risk animals include:
• For farmed and captive cervids:
fallen/culled farmed or captive cervids, defined as farmed or captive cervids found dead on the enclosed territory in which they are kept, during transport or at slaughterhouse, as well as farmed or captive cervids killed for health/age reasons;
clinical/sick farmed or captive cervids, defined as farmed or captive cervids showing abnormal behavioural signs and/or locomotor disturbances and/or as being generally in poor condition;
slaughtered farmed cervids which have been declared unfit for human consumption.
• For wild and semi-domesticated cervids:
fallen/culled wild or semi-domesticated cervids, defined as cervids found dead in the wild as well as semi-domesticated cervids found dead or killed for health/age reasons;
road- or predator-injured or killed cervids, defined as wild or semi-domesticated cervids hit by road vehicles, by trains or attacked by predators;
clinical/sick wild and semi-domesticated cervids, defined as wild and semi-domesticated cervids which are observed as showing abnormal behavioural signs and/or locomotor disturbances and/or as being generally in poor health condition;
wild hunted cervids and slaughtered semi-domesticated cervids which have been declared unfit for human consumption.
The total number of tested cervids in Europe in 2018 (as reported to EFSA) was 41,322, with 80% of these (33,037) tested by Norway where seven new cases (six in reindeer and one in a moose) were confirmed.
The remaining 20% were tested by EU MSs, apart from 100 reindeer tested by Iceland. Twelve MSs reported tested cervids, ranging from four each by Austria and Hungary, to Romania, the MS with the largest throughput in the EU, which tested 2,387, 75% of them wild roe deer.
In 2018, the six MS conducting mandatory surveillance tested a total 5,110 cervids, of which 4,674 (91.5%) were wild animals, mostly roe deer and red deer and 436 (8.5%) were captive, farmed or semi-domesticated, with more than half of them being semi-domesticated reindeer tested in Finland (Table 7).
The most common target group was the ‘hunted/slaughtered fit for human consumption’ (HSHC) that is not a ‘risk animals’ category and that group accounted for 59.5% of all cervids tested by the six MS. The rest were risk animals in the different target groups (SUS: clinical suspect animals; RK: Road/ predator killed; FC: fallen/culled; HSNHC: hunted/slaughtered not fit for human consumption). There is a huge variability between countries in the proportion of cervids tested in the HSHC, ranging from 5% tested by Sweden to 94.2% by Latvia or 84.8% by Lithuania (Table 8).
Up to 20 September 2019, 28 cases have been reported in Europe: 19 wild reindeer, four moose and one red deer in Norway and since the mandatory surveillance started in 2018 one moose in Finland and three moose in Sweden. The first Finnish case was reported in March 2018 as a 15-year-old moose that was found dead in Kuhmo (Kainuu region), in Easter Finland, near the border with the Russian Federation. It was positive in brain using Bio-Rad and IDEXX ELISA rapid tests and negative in the tested lymph nodes (Korpenfelt, 2019).
The first Swedish case was reported on 26 March 2019 as a 16-year-old female, euthanised because it was emaciated and showed circling and abnormal behaviour in the area of Arjeplog, municipality of Norrbotten, north of Sweden, ~ 400 km from the closest area where Norwegian cases in moose had been identified and ~ 950 km from where the Finnish moose case was found. It was positive using Bio-Rad TeSeE ELISA, Bio-Rad TeSeE WB and in immunohistochemistry in the brainstem and negative using Bio-Rad TeSeE ELISA and IHC in the retropharyngeal lymph node (Gavier-Widen, 2019). Preliminary results show a similar presentation to that of the CWD observed in moose in Norway and in Finland, but further analyses are needed to confirm possible similarities.
The second Swedish moose, also a 16-year-old female that was emaciated and showing behavioural changes, was found in Arvidsjaur, 70 km from the first case, in late May 2019. It was positive using Bio-Rad TeSeE ELISA and Bio-Rad TeSeE WB in the brainstem and negative using BioRad TeSeE ELISA in the retropharyngeal lymph node (Gavier-Widen, 2019). The third Swedish moose was an at least 9-year-old female, shot during the normal hunting season in the same area as the two previous cases and without any signs of illness.8
It is premature to make any assessment of the effectiveness of the monitoring programme in the six selected countries. It is important to remember that the aims of the proposed surveillance system are twofold: (1) to detect disease in countries where CWD has not yet been detected, using a predefined design prevalence based on previous known occurrence in newly infected areas in NA; and (2) to estimate prevalence in areas where disease has been detected (EFSA BIOHAZ Panel, 2017).
The logistical constraints of implementing such a programme at national level cannot be underestimated, hence the slow start of some of the countries during the first year of implementation. However, the detection of three cases already in two of the six countries at early stages of the programme leads to two immediate and preliminary conclusions: (1) it is of paramount importance to conduct active surveillance for CWD to ascertain the actual distribution of the disease in susceptible species of European cervids; and (2) the distribution and prevalence of CWD in Europe may be underestimated as the three species known to be susceptible to CWD in Europe, namely reindeer, moose and red deer, only accounted for 5.8%, 17.3% and 19% of all cervids tested in the six countries in 2018, with one case in moose found during that period and only four of every 10 cervids tested so far have been from the high-risk target groups.
For example, in a large country with more than 100 PSU defined, assuming a perfect random sampling of PSU and risk animals within the PSU and the same surveillance results as in Finland in 2018, the prevalence of CWD in the subpopulation of moose in the fallen/culled risk category would be 1/176 = 0.57% (95% CI: 0.01–3.1%). There are no surveillance data for Sweden in 2019 with which to make similar estimations.
Table 7: Number of tested cervids for TSE in the EU and European Economic Area (EEA) reporting countries for the period 2016–2018. In parentheses, the number of CWD cases
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3.5.1. Concluding remarks
• A recent study analysing the data of the Nordfjella area estimated the apparent CWD prevalence at 1.2% of adults in the infected population of wild reindeer, while the estimated true prevalence was 1.6% (Viljugrein et al., 2019).
• The current mandatory surveillance programme in six EU MS has led to the detection of the first cases of CWD in the European Union, in a moose in Finland and in three moose in Sweden.
• Based on the available active and passive surveillance data from the EU as a whole, the overall situation of the disease is still unknown: CWD could be present in any of the other four MS under mandatory surveillance and/or in any of the other 22 MS not subject to mandatory surveillance. The available data on the prevalence of CWD in Sweden and Finland are still limited.
3.6. Risk factors for the spread of CWD in Europe
CWD in NA and Europe affects cervid species whose geographic ranges overlap with those of several other wild and domesticated species. Based on the experience gained in NA, CWD can be considered highly contagious, with infected individuals contributing to the spread of the disease through direct contact and/or through the shedding of the CWD agent(s) in the environment, where it remains infectious for a long time. Furthermore, the CWD agent(s) can be transported by other animal species (i.e. scavengers) or as a consequence of human activities, leading to a wider exposure of cervids and other potentially susceptible species to CWD. Therefore, among known prion diseases, CWD seems to have the widest potential species range, a notion which can have significant impact for understanding the biology of the CWD epidemics, for designing surveillance systems and control measures and for estimating the risks for food safety and human health.
As mentioned in Section 3.5, six EU MS are currently implementing mandatory surveillance. Due to the low throughput (data only available for 1 year of the 3-year cycle), no conclusions can yet be drawn about the prevalence of CWD in Finland and Sweden or the presence of disease in the remaining four countries. The uncertainty about the presence of the disease in the rest of Europe is even higher.
Except for the recent data from Norway, any information on host susceptibility, transmission and spread of CWD is based on the situation in NA. Previous European risk assessments (Defra, 2016a,b, 2018) have assumed that the disease, if it occurred in Europe, would have most likely been imported from NA and would therefore behave similarly in European cervid populations. However, the data emerging from the characterisation of the recently identified European cervid isolates (see Section 3.3) indicate that these European isolates are molecularly and biologically distinct from those identified in NA.
Given the uncertainties associated with the actual geographical distribution of CWD in Europe and the possible transmissibility of the different strains (known and unknown) in Europe, the following description of potential risk factors for the spread of CWD in Europe assumes two hypothetical scenarios, drawing on knowledge of CWD and other TSE in domestic animals and without any reference to specific locations where the disease is/might be present.
3.6.1. Scenario development
The description of the current scientific evidence on the characteristics of European CWD isolates (see Section 3.1) has implications for their potential capacity to spread naturally within cervid populations. In particular, the presence/absence of detectable PrPSc outside the CNS is thought to be an indication of the probability of spread under field conditions. While CNS involvement is a consistent feature of all clinical TSE cases regardless of species, the presence or absence of detectable PrPSc in peripheral tissues is more of a continuum, with some phenotypes presenting early accumulations of PrPSc, while others only accumulate limited amounts, or none. These differences may be associated either with strain or host genotype, or a combination of the two (for recent review of the cervid context, see Section 3.2.2 of the EFSA BIOHAZ Panel, 2018). For example, most cases of classical scrapie and NA CWD have widespread peripheral tissue involvement, the extent of which is affected by genotype and both are contagious under field conditions. BSE, H- and L-type BSE and atypical/Nor98 scrapie, conversely, have little or no detectable PrPSc in peripheral tissues (Benestad et al., 2003; Wells et al., 2005; Andreoletti et al., 2011; Stack et al., 2011; EFSA, 2014) and tend to present as individual cases within herds/flocks. (It is important to note that while the term ‘atypical’ is often applied to this latter phenotype, this does not mean that they necessarily share the same biochemical or biological properties, or zoonotic potential; see Appendix A.5) The NA elk, however, is in-between, with a low amounts of abnormal PrP deposition (Race et al., 2007) associated with longer incubation periods (Moore et al., 2018) and low prevalence (Mysterud and Edmunds, 2019). These differences allow the description for developing hypothetical epidemiological scenarios of what can be considered representative of the extremes of this phenotypic spectrum:
• A contagious form presenting with peripheral distribution of PrPSc/infectivity, similar to the wellknown presentation of CWD in NA and classical scrapie in small ruminants with susceptible PrP genotypes. It is assumed, for this scenario, that infected animals would be able to transmit disease horizontally under field conditions and that infection could also be spread via environmental contamination by either live animals (e.g. through saliva, urine, faeces) or carcass disintegration. Subsequent dissemination could occur as a result of human activity, fomites and/ or scavengers or via the feed chain.
• A non-contagious form presenting little or no detectable involvement of peripheral tissues, akin to BSE in cattle or atypical/Nor98 scrapie in small ruminants. It is assumed, for this scenario, that infection would be less likely to transmit horizontally under field conditions and that environmental contamination by live animals would be minimal. Environmental contamination could still arise from the CNS of disintegrating carcasses and be spread via human activity, fomites and/or scavengers or via the feed chain.
Disease can spread by:
• extending the geographic extent of a focus to a new area/region/country: mainly by natural migration of infected animals and by the translocation of infected cervids by humans;
• once introduced into a herd or population, the local spread of the agent is associated with the rate of contacts between animals or the environmental contamination. Behavioural and social factors of the different susceptible and non-susceptible species present explain the transmission rate of the disease and the consequent spread to non-infected animals within the population of interest.
In both cases, the agent(s) must be released from the infected individual(s), hence allowing other non-infected animals to be exposed resulting in further release or translocation and giving rise to:
• a new individual being infected that, if it is of a susceptible species, will develop clinical disease and will be capable of shedding infectivity in excreta throughout most of the incubation period if the disease phenotype includes PrP accumulation in peripheral tissues
• a subclinical or carrier animal, in which some abnormal PrP accumulates, but the animal does not develop clinical disease within its lifetime. Such animals may or may not shed infectivity in excreta, potentially over prolonged periods.
• a passive carrier, in which infection does not establish itself and infected material passes through the gut and into the environment via faeces in a relatively short time postconsumption (e.g. non-susceptible species such as predators, scavengers and carrion birds)
The two working scenarios may or not reflect the ability and the extent to which any of them can contribute to the transmission and spread of the disease. These scenarios do not account either for the possibility of the biological properties of an isolate changing on passage through another host species (EFSA BIOHAZ Panel, 2015).
3.6.2. Identification of risk factors
In the context of this Opinion, a risk factor for the spread of CWD in Europe will be considered as any feature that increases the likelihood of a non-infected animal becoming exposed and infected in areas where the disease has already been identified, or in areas not yet considered as infected.
The risk factors for the spread of prion disease have been widely described in the published literature and extensively reviewed in publications and published national risk assessments (most recently in UK and Norway). It is beyond the scope of this Opinion to undertake a further extensive literature review, particularly as it is likely that European and NA isolates differ from one another (see Sections 3.1 and 3.2) and may present with different, and as yet unknown, risks.
The table of risk factors below (Table 9) is a summary of all previously identified risks for the spread of prion disease assessed against the two hypothetical scenarios. The criteria applied for the inclusion of an ‘identified risk factor’ for either scenario are based on three components:
1) The biological plausibility of the release of the agent or of the exposure to the agent from an infected individual even if there is only a theoretical likelihood of occurrence (a theoretical risk factor).
2) A hypothesis raised from the field observation of the distribution of the disease based on descriptive epidemiological studies (a hypothetical risk factors).
3) The reporting of a risk factor as an output of analytical epidemiological studies in which the association between its exposure and the disease occurrence has been shown to be statistically significant (a confirmed risk factor).
The studies included in Table 9 have been classified, based on their design (Rothman et al., 2008; Dohoo et al., 2009) into intervention vs observational studies. The latter are further distinguished into analytical studies that are designed to test aetiological hypotheses and quantify the effect of risk factors (i.e. cohort studies, case–control studies and cross-sectional studies) vs descriptive studies (i.e. case reports and case series) that are considered as hypothesis-screening studies. By combining descriptive data and assumptions, epidemiological hypotheses may also be supported (but not tested) by mathematical simulation models.
The biological plausibility of the involvement of a factor in the spread may be suggested by nonepidemiological studies or qualitative risk assessments or reviews, so these were considered as sources able to suggest ‘theoretical risk factors’. Due to the uncertainties associated with both the unknown European epidemiological situation and the differences between involved strains, it is not possible to assess the epidemiological relevance of any of the listed risk factors even in the NA context, let alone in the European one.
However, the strength of the evidence for the causal role of each group of risk factors can be appraised. For this purpose, a score-based ranking (as proposed by Dohoo et al., 2009) has been applied based on the different informative potential of the studies:
• score = A: if the risk factor has been proposed through intervention studies (strongest evidence);
• score = B: if through cohort studies;
• score = C: if through case–control studies;
• score = D: if through cross-sectional studies;
• score = E: if through descriptive studies (i.e. an epidemiologically screened hypothesis) or mathematical simulation models;
• score = F: if through biologically plausible hypotheses alone, based on non-epidemiological studies or qualitative risk assessments or reviews (weakest evidence).
Based on the above inclusion criteria, Table 9 shows a list of groups of potential risk factors for the spread of CWD in Europe within or between areas/regions/countries, with the indication of the studies used to source each risk factor from the literature and their score. Finally, all factors depending on, or affected, by human practices (with the exception of rearing cervids in captivity) and therefore possible targets for preventive measures, have been highlighted.
A general conceptual map (Figure 1) has been developed to show all the factors mentioned in the list and to summarise the relationships among them within theoretical risk pathways. This map also highlights potential targets for interventions that could be used as preventive measures against the spread of disease.
Table 9: Groups of risk factors according to the two working scenarios (I: contagious animal vs II: non-contagious animal)
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Figure 1: Conceptual map summarising the relationship among risk factors within risk pathways and potential targets for preventive measures
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3.6.3. Concluding remarks
• The identification of risk factors associated with the spread of the disease can only be based on the epidemiological and biological understanding of NA CWD outbreaks, although the biological characterisation of the European isolates indicates that they differ from the known NA strains.
• The presence/absence of detectable PrPSc in the peripheral tissues as well as the CNS of affected animals can be used as an indicator of the probability of natural spread and animals assigned to different categories based on their pathogenesis. Both infected carriers and passive carriers are thought to be involved in the dissemination of the agent.
• Two distinct, hypothetical working scenarios have been built on these categories: a contagious form (Scenario 1) affecting animals which can spread infectivity through direct contacts with other animals and/or contamination of the environment and a non-contagious form (Scenario 2) that is transmitted through environmental contamination from infected carcasses or via human activity, scavengers or via the feed chain.
• Thirteen main groups of risk factors have been identified based on their biological plausibility to spread CWD. Some of them are supported by epidemiological evidence from NA CWD.
• The only risk factors for the spread of CWD affecting exclusively Scenario 1 refer to animal to animal contact which will increase through the aggregation of live animals, promoted, or not, by human activities.
• All other risk factors refer to natural or man-mediated movement or translocation of wild or farmed/free ranging animals and to environmental contamination and the subsequent exposure of animals to contaminated soil or vegetation. This can occur at the point of contamination (close to a fallen animal) or following translocation of contaminated materials by humans or scavengers. These risks will also vary depending on the social structures of different species and by habitat and the geography of specific regions. In wild populations, the co-existence of different species makes it important to consider all the identified risk factors in both scenarios.
• Risk reduction through intervention would be possible for some man-mediated risk factors, namely activities leading to the translocation or aggregation of both wild and farmed live animals, as well as fallen stock management and appropriate disposal of carcasses and slaughter by-products.
3.7. Uncertainty analysis
The sources of uncertainty associated with the available data have been summarised in tabular format (Table 10), describing the nature or cause of the uncertainty. The factors contributing to the list of uncertainties are mostly missing or incomplete data on disease prevalence, pathogenesis and isolate characterisation, affecting the entire Opinion and the answers to all of the ToRs.
Table 10: Sources of uncertainty identified in the risk assessment
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***> It is therefore not possible to perform a risk assessment of CWD in humans.
3.4.1. Epidemiological studies
The caveats associated with using epidemiological studies to investigate the association between human and animals TSE have all been previously highlighted (EFSA BIOHAZ Panel, 2015). These include the reliability of disease occurrence estimates from surveillance data and the inability to control for the effects of potential confounding factors, such as CWD diversity, host genetics, lag time (potential incubation period of human TSE), ecological fallacy and exposure misclassification.
A systematic review of the current evidence on the transmissibility of CWD prions to humans has been published recently (Waddell et al., 2018), using the criteria set-up through the Grading of Recommendations Assessment, Development and Evaluation (GRADE) (Schu€nemann et al., 2013). Three types of studies were assessed: epidemiological studies, in vitro and in vivo experiments. The GRADE of the quality of evidence for the five epidemiological studies assessed suggested that future evidence may be inconsistent with the conclusions of the currently available studies. For the two studies on macaques (see Section 3.3.2), GRADE indicated that there is limited confidence that the results and estimates presented will not change with future research (mainly due to the limited number of studies and observations available). GRADE of the seven studies on humanised transgenic mice, which provided no evidence to support the possibility of transmission of CWD prions to humans, indicated that there is some confidence the overall conclusions of this research will not change with future research. The authors concluded that ‘future discovery of CWD transmission to humans cannot be entirely ruled out on the basis of current studies, particularly in the light of possible decades-long incubation periods for CWD prions in humans and recommended to exercise caution when handling potentially contaminated material and explore CWD management opportunities’.
Among the more recent studies not included in the systematic review by Waddell et al. (2018), Abrams et al. (2018) have investigated the rates of human prion disease in States of the USA with and without CWD, to examine the possibility of undetermined zoonotic transmission. Although final results of this study have not been published yet, the authors concluded that ‘while higher prion disease mortality rates in certain categories of states with CWD in free-ranging cervids were noted, additional stratified analyses did not reveal markedly elevated rates for potentially sensitive subgroups that would be suggestive of zoonotic transmission. Unknown confounding factors or other biases may explain state- by-state differences in prion disease mortality’.
www.efsa.europa.eu/efsajournal 26 EFSA Journal 2019;17(11):5863
Chronic Wasting Disease (CWD) III
Maddox et al. (2019) conducted a retrospective cohort study of 1,546 residents in 15 counties of the State of Wisconsin in which CWD has been confirmed among harvested free-ranging deer. By linking three databases, the study aimed to evaluate causes of mortality in individuals potentially exposed to CWD. The results of the study have not been published yet but preliminary results identified individuals that consumed CWD-positive deer but with no matches in the National Prion Disease Pathology Surveillance Center (NPDPSC) neuropathology database. Due to the long incubation period, should transmission to humans occur, many years of vital status tracking are needed.
The potential variability of phenotypes of prion disease in humans and the potential for association with a zoonotic strain of CWD is an increasing area of concern in CWD-endemic regions given the impossibility of knowing what the phenotype of human CWD prions would present with or whether they would be distinct from sporadic CJD cases. One example of a study looking at this aspect is the current analysis of the molecular diversity of CJD cases in patients who resided in Alberta and Saskatchewan (Canada) at their time of death (Myskiw et al., 2019). In a similar study, frozen brain tissues from all available sCJD cases archived in the NPDPSC from a US State with a high incidence of CWD are being analysed, looking for unusual patterns, characteristics and/or distribution of PrPSc in comparison with sCJD samples from States that have not detected CWD (Liu et al. (2019)).
3.4.2. Exposure assessment
There are two distinct routes of potential exposure of humans to the CWD agent(s):
1) Handling and manipulation by professionals (including industrial workers), hunters, consumers, etc., of dead bodies, carcasses, meat cuts, animal by-products including risk material and meat, meat prod...
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3.4.4.
Systematic testing: Only allowing human consumption of meat, meat products and offal sourced from animals that have been tested negative for CWD.
Targeted measures: Prohibition of harvesting/hunting susceptible species or the introduction of compulsory testing of animals before human consumption in/from declared infected premises/ areas (e.g. a farm, or a surveillance PSU (Section 3.6), region, country, etc.). Systematic removal of high-risk tissues from all cervids intended for human consumption with no requirement for testing.
Concluding remarks
Due to uncertainties and lack of data, it is not possible to conduct a risk assessment of CWD in humans and to directly quantify the human risk at either individual or population levels. The risk to humans through consumption of meat, meat products and offal derived from CWD- infected cervids cannot be directly assessed; only the probability of exposure to the CWD agent(s).
Lack of comprehensive data on both the tissue distribution of infectivity in European cases and the prevalence of the CWD gent in each of the species, increases the uncertainty around human exposure and related risk factors.
The available epidemiological studies have not shown any evidence of association between human TSE and NA CWD. However, these studies suffer from many methodological and logistic constraints.
A recent systematic review concluded that the long incubation periods in human TSE mean that current studies do not definitely exclude any potential for CWD to transmit to humans. Even if the specific tissues harbouring most of the infectivity were removed from the food chain, therefore reducing the human dietary exposure to infectivity, consumers would still be exposed to the CWD agent(s) via consumption of meat and meat products from infected animals.
Exclusion from the food chain of the whole carcass of any infected animal would be required to eliminate human dietary exposure. This could be facilitated by the preliminary testing of animals intended for consumption and/or the prohibition of harvesting or hunting susceptible species in infected premises/areas.
See full text;
i have spoken with Stefanie Czub and Professor Aguzzi, whom toured her lab afterwards, about these studies. the transmission studies were valid. plus, we know that cwd zoonosis would NOT look like nvCJD, but would look like sporadic CJD of some type.
***> It is therefore not possible to perform a risk assessment of CWD in humans.
a review of science as follows;
> 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).***
snip...see more;
Chronic Wasting Disease In Cervids: Zoonosis there from, has it already happened, and is it being misdiagnosed as sporadic cjd?
> 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).***
Chronic Wasting Disease CWD TSE Prion aka mad deer disease zoonosis
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.
ZOONOTIC CHRONIC WASTING DISEASE CWD TSE PRION UPDATE
Prion 2017 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
PRION 2018 CONFERENCE
Oral transmission of CWD into Cynomolgus macaques: signs of atypical disease, prion conversion and infectivity in macaques and bio-assayed transgenic mice
Hermann M. Schatzl, Samia Hannaoui, Yo-Ching Cheng, Sabine Gilch (Calgary Prion Research Unit, University of Calgary, Calgary, Canada) Michael Beekes (RKI Berlin), Walter Schulz-Schaeffer (University of Homburg/Saar, Germany), Christiane Stahl-Hennig (German Primate Center) & Stefanie Czub (CFIA Lethbridge).
To date, BSE is the only example of interspecies transmission of an animal prion disease into humans. The potential zoonotic transmission of CWD is an alarming issue and was addressed by many groups using a variety of in vitro and in vivo experimental systems. Evidence from these studies indicated a substantial, if not absolute, species barrier, aligning with the absence of epidemiological evidence suggesting transmission into humans. Studies in non-human primates were not conclusive so far, with oral transmission into new-world monkeys and no transmission into old-world monkeys. Our consortium has challenged 18 Cynomolgus macaques with characterized CWD material, focusing on oral transmission with muscle tissue. Some macaques have orally received a total of 5 kg of muscle material over a period of 2 years.
After 5-7 years of incubation time some animals showed clinical symptoms indicative of prion disease, and prion neuropathology and PrPSc deposition were detected in spinal cord and brain of some euthanized animals. PrPSc in immunoblot was weakly detected in some spinal cord materials and various tissues tested positive in RT-QuIC, including lymph node and spleen homogenates. To prove prion infectivity in the macaque tissues, we have intracerebrally inoculated 2 lines of transgenic mice, expressing either elk or human PrP. At least 3 TgElk mice, receiving tissues from 2 different macaques, showed clinical signs of a progressive prion disease and brains were positive in immunoblot and RT-QuIC. Tissues (brain, spinal cord and spleen) from these and pre-clinical mice are currently tested using various read-outs and by second passage in mice. Transgenic mice expressing human PrP were so far negative for clear clinical prion disease (some mice >300 days p.i.). In parallel, the same macaque materials are inoculated into bank voles.
Taken together, there is strong evidence of transmissibility of CWD orally into macaques and from macaque tissues into transgenic mouse models, although with an incomplete attack rate.
The clinical and pathological presentation in macaques was mostly atypical, with a strong emphasis on spinal cord pathology.
Our ongoing studies will show whether the transmission of CWD into macaques and passage in transgenic mice represents a form of non-adaptive prion amplification, and whether macaque-adapted prions have the potential to infect mice expressing human PrP.
Our ongoing studies will show whether the transmission of CWD into macaques and passage in transgenic mice represents a form of non-adaptive prion amplification, and whether macaque-adapted prions have the potential to infect mice expressing human PrP.
The notion that CWD can be transmitted orally into both new-world and old-world non-human primates asks for a careful reevaluation of the zoonotic risk of CWD..
***> The notion that CWD can be transmitted orally into both new-world and old-world non-human primates asks for a careful reevaluation of the zoonotic risk of CWD. <***
READING OVER THE PRION 2018 ABSTRACT BOOK, LOOKS LIKE THEY FOUND THAT from this study ;
P190 Human prion disease mortality rates by occurrence of chronic wasting disease in freeranging cervids, United States
Abrams JY (1), Maddox RA (1), Schonberger LB (1), Person MK (1), Appleby BS (2), Belay ED (1) (1) Centers for Disease Control and Prevention (CDC), National Center for Emerging and Zoonotic Infectious Diseases, Atlanta, GA, USA (2) Case Western Reserve University, National Prion Disease Pathology Surveillance Center (NPDPSC), Cleveland, OH, USA..
SEEMS THAT THEY FOUND Highly endemic states had a higher rate of prion disease mortality compared to non-CWD
states.
states.
AND ANOTHER STUDY;
P172 Peripheral Neuropathy in Patients with Prion Disease
Wang H(1), Cohen M(1), Appleby BS(1,2) (1) University Hospitals Cleveland Medical Center, Cleveland, Ohio (2) National Prion Disease Pathology Surveillance Center, Cleveland, Ohio..
IN THIS STUDY, THERE WERE autopsy-proven prion cases from the National Prion Disease Pathology Surveillance Center that were diagnosed between September 2016 to March 2017,
AND
included 104 patients. SEEMS THEY FOUND THAT The most common sCJD subtype was MV1-2 (30%), followed by MM1-2 (20%),
AND
THAT The Majority of cases were male (60%), AND half of them had exposure to wild game.
snip…
see more on Prion 2017 Macaque study from Prion 2017 Conference and other updated science on cwd tse prion zoonosis below…terry
PRION 2019 ABSTRACTS
1. Interspecies transmission of the chronic wasting disease agent
Justin Greenlee
Virus and Prion Research Unit, National Animal Disease Center, USDA Agriculture Research Service
ABSTRACT
The presentation will summarize the results of various studies conducted at our research center that assess the transmissibility of the chronic wasting disease (CWD) agent to cattle, pigs, raccoons, goats, and sheep. This will include specifics of the relative attack rates, clinical signs, and microscopic lesions with emphasis on how to differentiate cross-species transmission of the CWD agent from the prion diseases that naturally occur in hosts such as cattle or sheep. Briefly, the relative difficulty of transmitting the CWD agent to sheep and goats will be contrasted with the relative ease of transmitting the scrapie agent to white-tailed deer.
53. Evaluation of the inter-species transmission potential of different CWD isolates
Rodrigo Moralesa, Carlos Kramma,b, Paulina Sotoa, Adam Lyona, Sandra Pritzkowa, Claudio Sotoa
aMitchell Center for Alzheimer’s disease and Related Brain Disorders, Dept. of Neurology, McGovern School of Medicine University of Texas Health Science Center at Houston, TX, USA; bFacultad de Medicina, Universidad de los Andes, Santiago, Chile
ABSTRACT
Chronic Wasting Disease (CWD) has reached epidemic proportions in North America and has been identified in South Korea and Northern Europe. CWD-susceptible cervid species are known to share habitats with humans and other animals entering the human food chain. At present, the potential of CWD to infect humans and other animal species is not completely clear. The exploration of this issue acquires further complexity considering the differences in the prion protein sequence due to species-specific variations and polymorphic changes within species. While several species of cervids are naturally affected by CWD, white-tailed deer (WTD) is perhaps the most relevant due to its extensive use in hunting and as a source of food. Evaluation of inter-species prion infections using animals or mouse models is costly and time consuming. We and others have shown that the Protein Misfolding Cyclic Amplification (PMCA) technology reproduces, in an accelerated and inexpensive manner, the inter-species transmission of prions while preserving the strain features of the input PrPSc. In this work, we tested the potential of different WTD-derived CWD isolates to transmit to humans and other animal species relevant for human consumption using PMCA. For these experiments, CWD isolates homozygous for the most common WTD-PrP polymorphic changes (G96S) were used (96SS variant obtained from a pre-symptomatic prion infected WTD). Briefly, 96GG and 96SS CWD prions were adapted in homologous or heterologous substrate by PMCA through several (15) rounds. End products, as well as intermediates across the process, were tested for their inter-species transmission potentials. A similar process was followed to assess seed-templated misfolding of ovine, porcine, and bovine PrPC. Our results show differences on the inter-species transmission potentials of the four adapted materials generated (PrPC/PrPSc polymorphic combinations), being the homologous combinations of seed/substrate the ones with the greater apparent zoonotic potential. Surprisingly, 96SS prions adapted in homologous substrate were the ones showing the easiest potential to template PrPC misfolding from other animal species. In summary, our results show that a plethora of different CWD isolates, each comprising different potentials for inter-species transmission, may exist in the environment. These experiments may help to clarify an uncertain and potentially worrisome public health issue. Additional research in this area may be useful to advise on the design of regulations intended to stop the spread of CWD and predict unwanted zoonotic events.
56. Understanding chronic wasting disease spread potential for at-risk species
Catherine I. Cullingham, Anh Dao, Debbie McKenzie and David W. Coltman
Department of Biological Sciences, University of Alberta, Edmonton AB, Canada
CONTACT Catherine I. Cullingham cathy.cullingham@ualberta.ca
ABSTRACT
Genetic variation can be linked to susceptibility or resistance to a disease, and this information can help to better understand spread-risk in a population. Wildlife disease incidence is increasing, and this is resulting in negative impacts on the economy, biodiversity, and in some instances, human health. If we can find genetic variation that helps to inform which individuals are susceptible, then we can use this information on at-risk populations to better manage negative consequences. Chronic wasting disease, a fatal, transmissible spongiform encephalopathy of cervids (both wild and captive), continues to spread geographically, which has resulted in an increasing host-range. The disease agent (PrPCWD) is a misfolded conformer of native cellular protein (PrPC). In Canada, the disease is endemic in Alberta and Saskatchewan, infecting primarily mule deer and white-tail deer, with a smaller impact on elk and moose populations. As the extent of the endemic area continues to expand, additional species will be exposed to this disease, including bison, bighorn sheep, mountain goat, and pronghorn antelope. To better understand the potential spread-risk among these species, we reviewed the current literature on species that have been orally exposed to CWD to identify susceptible and resistant species. We then compared the amino acid polymorphisms of PrPC among these species to determine whether any sites were linked to susceptibility or resistance to CWD infection. We sequenced the entire PrP coding region in 578 individuals across at-risk populations to evaluate their potential susceptibility. Three amino acid sites (97, 170, and 174; human numbering) were significantly associated with susceptibility, but these were not fully discriminating. All but one species among the resistant group shared the same haplotype, and the same for the susceptible species. For the at-risk species, bison had the resistant haplotype, while bighorn sheep and mountain goats were closely associated with the resistant type. Pronghorn antelope and a newly identified haplotype in moose differed from the susceptible haplotype, but were still closely associated with it. These data suggest pronghorn antelope will be susceptible to CWD while bison are likely to be resistant. Based on this data, recommendations can be made regarding species to be monitored for possible CWD infection.
KEYWORDS: Chronic wasting disease; Prnp; wildlife disease; population genetics; ungulates
Thursday, May 23, 2019
Prion 2019 Emerging Concepts CWD, BSE, SCRAPIE, CJD, SCIENTIFIC PROGRAM Schedule and Abstracts
see full Prion 2019 Conference Abstracts
THURSDAY, OCTOBER 04, 2018
Cervid to human prion transmission 5R01NS088604-04 Update
snip…full text;
SATURDAY, FEBRUARY 09, 2019
Experts: Yes, chronic wasting disease in deer is a public health issue — for people
FRIDAY, JULY 26, 2019
Chronic Wasting Disease in Cervids: Implications for Prion Transmission to Humans and Other Animal Species
THURSDAY, AUGUST 08, 2019
Raccoons accumulate PrPSc after intracranial inoculation with the agents of chronic wasting disease (CWD) or transmissible mink encephalopathy (TME) but not atypical scrapie
*** 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).***
FRIDAY, JULY 26, 2019
Chronic Wasting Disease in Cervids: Implications for Prion Transmission to Humans and Other Animal Species
THE FULL MONTY
***> MAD DOGS AND ENGLISHMEN BSE, SCRAPIE, CWD, CJD, TSE PRION A REVIEW 2019
BSE INQUIRY EVIDENCE
Why did the appearance of new TSEs in animals matter so much? It has always been known that TSEs will transfer across species boundaries. The reason for this was never known until the genetic nature of the prion gene was fully investigated and found to be involved. The gene is found to have well preserved sites and as such there is a similar gene throughout the animal kingdom...and indeed a similar gene is found in insects! It is NOT clear that the precise close nature of the PrP gene structure is essention for low species barriers. Indeed it is probably easier to infect cats with BSE than it is to infect sheep. As such it is not clear that simply because it is possible to infect BSE from cattle into certain monkeys then other apes will necessarily be infectable with the disease. One factor has stood out, however, and that is that BSE, when inoculated into mice would retain its apparent nature of disease strain, and hence when it was inoculated back into cattle, then the same disease was produced. Similarly if the TSE from kudu was inoculated into mice then a similar distribution of disease in the brain of the mouse is seen as if BSE had been inoculated into the mouse. This phenomenon was not true with scrapie, in which the transmission across a species barrier was known to lose many of the scrapie strain phenomena in terms of incubation period or disease histopathology. This also suggested that BSE was not derived from scrapie originally but we probably will never know.
------------------------------------------------------------------------
TSE in wild UK deer? The first case of BSE (as we now realise) was in a nyala in London zoo and the further zoo cases in ungulates were simply thought of as being interesting transmissions of scrapie initially. The big problem started to appear with animals in 1993-5 when it became clear that there was an increase in the CJD cases in people that had eaten deer although the statistics involved must have been questionable. The reason for this was that the CJD Surveillance was well funded to look into the diet of people dying of CJD. This effect is not clear with vCJD...if only because the numbers involved are much smaller and hence it is difficult to gain enough statistics. They found that many other foods did not appear to have much association at all but that deer certainly did and as years went by the association actually became clearer. The appearance of vCJD in 1996 made all this much more difficult in that it was suddenly clearer that the cases of sporadic CJD that they had been checking up until then probably had nothing to do with beef...and the study decreased. During the period there was an increasing worry that deer were involved with CJD..
see references:
DEER BRAIN SURVEY
Subject: Re: DEER SPONGIFORM ENCEPHALOPATHY SURVEY & HOUND STUDY
Date: Fri, 18 Oct 2002 23:12:22 +0100
From: Steve Dealler
Reply-To: Bovine Spongiform Encephalopathy Organization: Netscape Online member
To: BSE-L@ References: <3daf5023 .4080804="" a="" fg_scanned="1" href="http://wt.net/" nbsp="" rel="noopener noreferrer" shape="rect" style="color: blue; cursor: pointer; line-height: 1.22em;" target="_blank">wt.net
Dear Terry,
An excellent piece of review as this literature is desparately difficult to get back from Government sites.
What happened with the deer was that an association between deer meat eating and sporadic CJD was found in about 1993.. The evidence was not great but did not disappear after several years of asking CJD cases what they had eaten. I think that the work into deer disease largely stopped because it was not helpful to the UK industry...and no specific cases were reported. Well, if you dont look adequately like they are in USA currenly then you wont find any!
Steve Dealler ===============
BSE Inquiry Steve Dealler
Management In Confidence
BSE: Private Submission of Bovine Brain Dealler
reports of sheep and calf carcasses dumped...
re-scrapie to cattle GAH Wells BSE Inquiry
https://web.archive.org/web/20090506043931/http://www.bseinquiry.gov.uk/files/yb/1993/12/09001001.pdf
https://web.archive.org/web/20090506065716/http://www.bseinquiry.gov.uk/files/yb/1995/06/21005001.pdf
Dr. Dealler goes rogue to confirm BSE
Confirmation BSE Dealler's mad cow
BSE vertical transmission
1993 cjd report finds relationship with eat venison and cjd increases 9 fold, let the cover up begin...tss
FINDINGS
*** 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 ;
GAME FARM INDUSTRY WANTS TO COVER UP FINDINGS OF INCREASE RISK TO CJD FROM CERVID
BSE INQUIRY
CJD9/10022
October 1994
Mr R.N. Elmhirst Chairman British Deer Farmers Association Holly Lodge Spencers Lane
BerksWell Coventry CV7 7BZ
Dear Mr Elmhirst,
CREUTZFELDT-JAKOB DISEASE (CJD) SURVEILLANCE UNIT REPORT
Thank you for your recent letter concerning the publication of the third annual report from the CJD Surveillance Unit. I am sorry that you are dissatisfied with the way in which this report was published.
The Surveillance Unit is a completely independant outside body and the Department of Health is committed to publishing their reports as soon as they become available. In the circumstances it is not the practice to circulate the report for comment since the findings of the report would not be amended.. In future we can ensure that the British Deer Farmers Association receives a copy of the report in advance of publication.
The Chief Medical Officer has undertaken to keep the public fully informed of the results of any research in respect of CJD. This report was entirely the work of the unit and was produced completely independantly of the the Department.
The statistical results reqarding the consumption of venison was put into perspective in the body of the report and was not mentioned at all in the press release. Media attention regarding this report was low key but gave a realistic presentation of the statistical findings of the Unit. This approach to publication was successful in that consumption of venison was highlighted only once by the media ie. in the News at one television proqramme.
I believe that a further statement about the report, or indeed statistical links between CJD and consumption of venison, would increase, and quite possibly give damaging credence, to the whole issue. From the low key media reports of which I am aware it seems unlikely that venison consumption will suffer adversely, if at all.
The BSE Inquiry / Statement No 324
Dr James Kirkwood (not scheduled to give oral evidence)
Statement to the BSE Inquiry
James K Kirkwood BVSc PhD FIBiol MRCVS
[This witness has not been asked to give oral evidence in Phase 1 of the Inquiry]
1. I became involved in the field of TSEs through my work as Head of the Veterinary Science Group at the Zoological Society of London’s Institute of Zoology. I held this post from November 1984 until June 1996, when I took up my present post at UFAW. During this time, concurrent with the BSE epidemic, cases of scrapie-like spongiform encephalopathies occurred in animals at the Zoological Society of London’s collections at Regent’s Park and Whipsnade and in other zoos. It was appropriate to investigate the epidemiology of these cases in order to try to determine the possible impact on zoo animals and breeding programmes, and to consider how the disease in zoo animals might be controlled.
2. Throughout the period from 1985 to March 1996, I worked at the Institute of Zoology (IoZ). I was Head of the Veterinary Science Group of the IoZ and Senior Veterinary Officer of the Zoological Society of London (ZSL). I was responsible for the provision of the veterinary service for the ZSL collections.
3. During the period from 1985 to March 1996, scrapie-like spongiform encephalopathies were diagnosed in the following animals which died, or were euthanased, at London Zoo and Whipsnade:
Animal Sex Date of Death Age (mos)
Arabian Oryx Oryx leucoryx F 24.3.89 38
Greater kudu Tragelaphus strepsiceros (Linda) F 18.8.89 30
Greater kudu (Karla) F 13.11.90 19 Greater kudu (Kaz) M 6.6.91 37
Greater kudu (Bambi) M 24.10.91 36
Greater kudu (346/90) M 26.2.92 18
Greater kudu (324/90) F 22.11.92 38
Cheetah Acinonyx jubatus (Michelle) F 22.12.93 91
All these cases were described in papers published in the scientific literature (as cited below).
EYES, RETINA, SHOULD NOT BE USED IN SCHOOLS, BAB, SOB, MRM,
BSE, PET FOOD, CRUSHED HEADS
IN PARTICULAR CRUSHED HEADS
YOU explained that imported crushed heads were extensively used in the petfood industry...
In particular I do not believe one can say that the levels of the scrapie agent in pet food are so low that domestic animals are not exposed.
BSE IN PETFOOD
1. The Secretary asked on 19 April whether I was content with the advice in para 3 of the record of the meeting on 17 March with the Parliamentary Secretary (Mr Thompson). The simple answer is ''not entirely''.
2. On occasions, material obtained from slaughterhouses will be derived from sheep affected with scrapie or cattle that may be incubating BSE for use in petfood manufacture. Some of this material must be classified as high risk since it contains brain, spinal cord, spleen or lymphatic glands.
Meldrum's notes on pet foods and materials used
IN CONFIDENCE CJD TO CATS...
It should be noted that under experimental conditions cats succumb to an encephalopathy after intracerebral inoculation of material derived from patients affected with Creutzfeldt-Jakob Disease.
Confidential BSE and __________________
3. I have thought very hard about whether the Branch should carry out a similar exercise with meat and meat products for human foods. On balance I do NOT think we should undertake it, but a final decision has not been taken and you may wish to discuss this further. ...
1st case natural FSE
NATURAL SPONGIFORM ENCEPHALOPATHY IN A DOMESTIC CAT
1. We have heard from MAFF that a domestic Siamese cat from the Bristol area has had spongiform encephalopathy confirmed. Although there are previous instances of experimental infection in cats, there have been no previous natural infections reported. The assumption must be the cat became infected by scrapie/BSE agent in it's food. ...
FSE and pharmaceuticals
1. An analysis by MCA Professional staff of the results to the questionnaire sent out to industry to obtain additional data about the use of animal materials of any origin in the manufacture of pharmaceutical products for human use, reveals that material of feline or canine origin is used in only two licensed products. In both instances the material is sourced from outside the U.K. and from areas currently believed to be free from B.S.E.
CONFIDENTIAL
Confidential cats/dogs and unsatisfactory posture MAFFs failure to assure key research
3. First, I am very uneasy about the relative lack of urgency and interest that MAFF appear to hold for getting the necessary research programme on BSE and related encephalopathies started, and getting it going fast. FOR EXAMPLE, MR BRADLEY of CVL said that there were difficulties in organizing transmission experiments from the brain of the cat which died of an encephalopathy in Bristol. There were arguments going on about who should pay for this work. Should it be MAFF, the Bristol Veterinary School or someone else? Dr. Tyrrell was clearly exasperated.
snip...
11. The Committee were even LESS FORTHCOMING on what their reaction might be if an encephalopathy is found in another species, perhaps in DOGS. Their first reaction was that, as with the cats, the first step could be to investigate whether this was really a new disease, or simply one that had not previously been recognized and to see whether it has any links to BSE, scrapie or other transmissible encephalopathies. Indeed, some members of the Committee seem to regard the whole question of another species as a hypothetical question to be addressed only when it happened. A rather UNSATISFACTORY POSTURE.
12. In advance of your meeting with Dr Tyrrell on Monday morning, I have not voiced my ANXIETIES about the support the Committee is receiving from MAFF to anyone OTHER THAN DR PICKLES. ...
SPONGIFORM ENCEPHALOPATHY IN A CAPTIVE PUMA
an article in yesterday's Times (attached) which suggested that the puma concerned had never ''eaten any part of a cow or sheep which, in the opinion of Government Scientists, could transmit the species to a different species''.
3. You explained to me that this was INCORRECT. The position was as set out in the briefing for Prime Minister's questions attached to Mr Taylor's note. The puma had probably been fed low quality beef meat in the form of split carcasses. ...
Subject: DEER SPONGIFORM ENCEPHALOPATHY SURVEY & HOUND STUDY Date: Thu, 17 Oct 2002 17:04:51 -0700 From: "Terry S. Singeltary Sr." Reply-To: Bovine Spongiform Encephalopathy To: BSE-L
Greetings BSE-L,
is there any other CWD surveys/testing in the UK on their deer? what sort of testing has been done to date on UK/EU deer? any input would be helpful... thank you
DEER SPONGIFORM ENCEPHALOPATHY SURVEY
3. This will be a low key study with no publicity to avoid unnecessary media interest. It will be carried out in two stages ;
(I) A small scale examination of around 30 deer brains to establish the normal histology of the healthy brain; and
(II) A larger scale random examination of 300 or more adult deer brains drawn from both deer farms and parks to establish whether there is any evidence of a cervine spongiform encephalopathy. ...
Ministry of Agriculture Fisheries and Food Veterinary Investigation Centre West House. Station Road. Thirsk Y07 IPZ Telephone: 0845·522065 Fax: 0845·525224
Your reference
Our reference RJH/ASB
Date 4 November 1992
DEER SPONGIFORM ENCEPHALOPATHY SURVEY
Dear Paul
I have now found time to review the 10 deer- brains collected from Mr Walker farm··via Winchester Via Winchester VIC. In answer to your specific question was there sufficient difference in preservation of brain tissue to warrant the extra effort involved in rapid brain removal on the farm, the answer is definitely "Yes." The original five brains (Winchester ref M487/11) showed varying degrees of autolytic vacuolation affecting both white and grey matter throughout the brain. vacuolation and separation of Purkinje cells and marked perivascular spaces. These artifacts made interpretation of subtle, specific pathological vacuolation more difficult. By contrast the second submission (Winchester reference N736/2) showed excellent preservation of white and grey matter. Any vacuolar Change present could be confidently interpreted as pathological albeit of unknown pathogenesis.
I can only reiterate the comments made by Gerald Wells and myself at the preliminary discussion at Weybridge in Autumn 1991. If the survey's purpose is an accurate histopathological interpretation of brain tissue. the material must be collected in a pristine state. This is particularly valid when looking for ar unrecognised and undefined spongiform encephalopathy in a new species. Deer brains are very large structures which take a lot of fixation and therefore must be handled sympathetically from the start. We have already seen the problems encountered in comparatively smaller hound brains where delayed fixation was a major limitation on interpretation of true pathological change.
The bottom line must be that if a pathologist's expertise is to be used, it is critical to collect artefact free brain material. If the politics or economics do not allow this, then I would suggest that an electron microscopy survey involving detection of scrapie associated fibrils would be much more appropriate.
Best wishes Yours sincerely
R J HIGGINS VIO 92/11.4/2.1
HOUND SURVEY
I am sorry, but I really could have been a co-signatory of Gerald's minute.
I do NOT think that we can justify devoting any resources to this study, especially as larger and more important projects such as the pathogenesis study will be quite demanding.
If there is a POLITICAL need to continue with the examination of hound brains then it should be passed entirely to the VI Service.
J W WILESMITH Epidemiology Unit 18 October 1991
Mr. R Bradley
cc: Mr. G A H Wells
***> 3.3. Mr R J Higgins in conjunction with Mr G A Wells and Mr A C Scott would by the end of the year, identify the three brains that were from the ''POSITIVE'' end of the lesion spectrum.
HOUND SURVEY PATHOLOGICAL REPORT (see positive results) and MAD DOGS AND ENGLISHMAN...
ya'll thought i was making this stuff up didn't ya...i don't make this stuff up!
It is clear that the designing scientists must also have shared Mr Bradley's surprise at the results because all the dose levels right down to 1 gram triggered infection.
second supplementary
Why did the appearance of new TSEs in animals matter so much? It has always been known that TSEs will transfer across species boundaries. The reason for this was never known until the genetic nature of the prion gene was fully investigated and found to be involved. The gene is found to have well preserved sites and as such there is a similar gene throughout the animal kingdom...and indeed a similar gene is found in insects! It is NOT clear that the precise close nature of the PrP gene structure is essention for low species barriers. Indeed it is probably easier to infect cats with BSE than it is to infect sheep. As such it is not clear that simply because it is possible to infect BSE from cattle into certain monkeys then other apes will necessarily be infectable with the disease. One factor has stood out, however, and that is that BSE, when inoculated into mice would retain its apparent nature of disease strain, and hence when it was inoculated back into cattle, then the same disease was produced. Similarly if the TSE from kudu was inoculated into mice then a similar distribution of disease in the brain of the mouse is seen as if BSE had been inoculated into the mouse. This phenomenon was not true with scrapie, in which the transmission across a species barrier was known to lose many of the scrapie strain phenomena in terms of incubation period or disease histopathology. This also suggested that BSE was not derived from scrapie originally but we probably will never know.
------------------------------------------------------------------------
TSE in wild UK deer? The first case of BSE (as we now realise) was in a nyala in London zoo and the further zoo cases in ungulates were simply thought of as being interesting transmissions of scrapie initially. The big problem started to appear with animals in 1993-5 when it became clear that there was an increase in the CJD cases in people that had eaten deer although the statistics involved must have been questionable. The reason for this was that the CJD Surveillance was well funded to look into the diet of people dying of CJD. This effect is not clear with vCJD...if only because the numbers involved are much smaller and hence it is difficult to gain enough statistics. They found that many other foods did not appear to have much association at all but that deer certainly did and as years went by the association actually became clearer. The appearance of vCJD in 1996 made all this much more difficult in that it was suddenly clearer that the cases of sporadic CJD that they had been checking up until then probably had nothing to do with beef...and the study decreased. During the period there was an increasing worry that deer were involved with CJD..
see references:
DEER BRAIN SURVEY
1993 cjd report finds relationship with eat venison and cjd increases 9 fold, let the cover up begin...tss
FINDINGS
*** 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 ;
GAME FARM INDUSTRY WANTS TO COVER UP FINDINGS OF INCREASE RISK TO CJD FROM CERVID
BSE INQUIRY
CJD9/10022
October 1994
Mr R.N. Elmhirst Chairman British Deer Farmers Association Holly Lodge Spencers Lane
BerksWell Coventry CV7 7BZ
Dear Mr Elmhirst,
CREUTZFELDT-JAKOB DISEASE (CJD) SURVEILLANCE UNIT REPORT
Thank you for your recent letter concerning the publication of the third annual report from the CJD Surveillance Unit. I am sorry that you are dissatisfied with the way in which this report was published.
The Surveillance Unit is a completely independant outside body and the Department of Health is committed to publishing their reports as soon as they become available. In the circumstances it is not the practice to circulate the report for comment since the findings of the report would not be amended.. In future we can ensure that the British Deer Farmers Association receives a copy of the report in advance of publication.
The Chief Medical Officer has undertaken to keep the public fully informed of the results of any research in respect of CJD. This report was entirely the work of the unit and was produced completely independantly of the the Department.
The statistical results reqarding the consumption of venison was put into perspective in the body of the report and was not mentioned at all in the press release. Media attention regarding this report was low key but gave a realistic presentation of the statistical findings of the Unit. This approach to publication was successful in that consumption of venison was highlighted only once by the media ie. in the News at one television proqramme..
I believe that a further statement about the report, or indeed statistical links between CJD and consumption of venison, would increase, and quite possibly give damaging credence, to the whole issue. From the low key media reports of which I am aware it seems unlikely that venison consumption will suffer adversely, if at all.
Management In Confidence
BSE: Private Submission of Bovine Brain Dealler
Subject: Re: DEER SPONGIFORM ENCEPHALOPATHY SURVEY & HOUND STUDY
Date: Fri, 18 Oct 2002 23:12:22 +0100
From: Steve Dealler
Reply-To: Bovine Spongiform Encephalopathy Organization: Netscape Online member
To: BSE-L@ References: <3daf5023 .4080804="" a="" fg_scanned="1" href="http://wt.net/" nbsp="" rel="noopener noreferrer" shape="rect" style="color: blue; cursor: pointer; line-height: 1.22em;" target="_blank">wt.net
Dear Terry,
An excellent piece of review as this literature is desparately difficult to get back from Government sites.
What happened with the deer was that an association between deer meat eating and sporadic CJD was found in about 1993. The evidence was not great but did not disappear after several years of asking CJD cases what they had eaten. I think that the work into deer disease largely stopped because it was not helpful to the UK industry...and no specific cases were reported. Well, if you dont look adequately like they are in USA currenly then you wont find any!
Steve Dealler
Stephen Dealler is a consultant medical microbiologist deal@airtime.co.uk
===============
https://caninespongiformencephalopathy.blogspot.com/2010/03/canine-spongiform-encephalopathy-aka.html
*** DEFRA TO SINGELTARY ON HOUND STUDY AND BSE 2001 ***
DEFRA Department for Environment, Food & Rural Affairs Area 307, London, SW1P 4PQ Telephone: 0207 904 6000 Direct line: 0207 904 6287 E-mail: h.mcdonagh.defra.gsi.gov.uk GTN: FAX: Mr T S Singeltary P.O. Box Bacliff Texas USA 77518 21 November 2001
Dear Mr Singeltary
TSE IN HOUNDS Thank you for e-mail regarding the hounds survey. I am sorry for the long delay in responding. As you note, the hound survey remains unpublished. However the Spongiform Encephalopathy Advisory Committee (SEAC), the UK Government's independent Advisory Committee on all aspects related to BSE-like disease, gave the hound study detailed consideration at their meeting in January 1994. As a summary of this meeting published in the BSE inquiry noted, the Committee were clearly concerned about the work that had been carried out, concluding that there had clearly been problems with it, particularly the control on the histology, and that it was more or less inconclusive. However was agreed that there should be a re-evaluation of the pathological material in the study.
Later, at their meeting in June 95, The Committee re-evaluated the hound study to see if any useful results could be gained from it. The Chairman concluded that there were varying opinions within the Committee on further work. It did not suggest any further transmission studies and thought that the lack of clinical data was a major weakness.
Overall, it is clear that SEAC had major concerns about the survey as conducted. As a result it is likely that the authors felt that it would not stand up to peer review and hence it was never published. As noted above, and in the detailed minutes of the SEAC meeting in June 95, SEAC considered whether additional work should be performed to examine dogs for evidence of TSE infection. Although the Committee had mixed views about the merits of conducting further work, the Chairman noted that when the Southwood Committee made their recommendation to complete an assessment of possible spongiform disease in dogs, no TSEs had been identified in other species and hence dogs were perceived as a high risk population and worthy of study. However subsequent to the original recommendation, made in 1990, a number of other species had been identified with TSE ( e.g. cats) so a study in hounds was less critical.
For more details see- http://www.bseinquiry.gov.uk/files/yb/1995/06/21005001.pdf
new url;
As this study remains unpublished, my understanding is that the ownership of the data essentially remains with the original researchers. Thus unfortunately, I am unable to help with your request to supply information on the hound survey directly. My only suggestion is that you contact one of the researchers originally involved in the project, such as Gerald Wells. He can be contacted at the following address. Dr Gerald Wells, Veterinary Laboratories Agency, New Haw, Addlestone, Surrey, KT 15 3NB, UK
You may also wish to be aware that since November 1994 all suspected cases of spongiform encephalopathy in animals and poultry were made notifiable. Hence since that date there has been a requirement for vets to report any su
===============
U.S.A. 50 STATE BSE MAD COW CONFERENCE CALL Jan. 9, 2001
Subject: BSE--U.S. 50 STATE CONFERENCE CALL Jan. 9, 2001
Date: Tue, 9 Jan 2001 16:49:00 -0800
From: "Terry S. Singeltary Sr."
Reply-To: Bovine Spongiform Encephalopathy
snip...
[host Richard Barns] and now a question from Terry S. Singeltary of CJD Watch.
[TSS] yes, thank you, U.S. cattle, what kind of guarantee can you give for serum or tissue donor herds?
[no answer, you could hear in the back ground, mumbling and 'we can't. have him ask the question again.]
[host Richard] could you repeat the question?
[TSS] U.S. cattle, what kind of guarantee can you give for serum or tissue donor herds?
[not sure whom ask this] what group are you with?
[TSS] CJD Watch, my Mom died from hvCJD and we are tracking CJD world-wide.
[not sure who is speaking] could you please disconnect Mr. Singeltary
[TSS] you are not going to answer my question?
[not sure whom speaking] NO
snip...see full archive and more of this;
===============
THURSDAY, SEPTEMBER 26, 2019
Veterinary Biologics Guideline 3.32E: Guideline for minimising the risk of introducing transmissible spongiform encephalopathy prions and other infectious agents through veterinary biologics
snip...full text;
MONDAY, FEBRUARY 25, 2019
***> MAD DOGS AND ENGLISHMEN BSE, SCRAPIE, CWD, CJD, TSE PRION A REVIEW 2019
SATURDAY, FEBRUARY 23, 2019
Chronic Wasting Disease CWD TSE Prion and THE FEAST 2003 CDC an updated review of the science 2019
TUESDAY, NOVEMBER 04, 2014
Six-year follow-up of a point-source exposure to CWD contaminated venison in an Upstate New York community: risk behaviours and health outcomes 2005–2011
Authors, though, acknowledged the study was limited in geography and sample size and so it couldn't draw a conclusion about the risk to humans. They recommended more study. Dr. Ermias Belay was the report's principal author but he said New York and Oneida County officials are following the proper course by not launching a study. "There's really nothing to monitor presently. No one's sick," Belay said, noting the disease's incubation period in deer and elk is measured in years. "
Transmission Studies
Mule deer transmissions of CWD were by intracerebral inoculation and compared with natural cases {the following was written but with a single line marked through it ''first passage (by this route)}....TSS
resulted in a more rapidly progressive clinical disease with repeated episodes of synocopy ending in coma. One control animal became affected, it is believed through contamination of inoculum (?saline). Further CWD transmissions were carried out by Dick Marsh into ferret, mink and squirrel monkey. Transmission occurred in ALL of these species with the shortest incubation period in the ferret.
snip....
Prion Infectivity in Fat of Deer with Chronic Wasting Disease▿
Brent Race#, Kimberly Meade-White#, Richard Race and Bruce Chesebro* + Author Affiliations
In mice, prion infectivity was recently detected in fat. Since ruminant fat is consumed by humans and fed to animals, we determined infectivity titers in fat from two CWD-infected deer. Deer fat devoid of muscle contained low levels of CWD infectivity and might be a risk factor for prion infection of other species.
Prions in Skeletal Muscles of Deer with Chronic Wasting Disease
Here bioassays in transgenic mice expressing cervid prion protein revealed the presence of infectious prions in skeletal muscles of CWD-infected deer, demonstrating that humans consuming or handling meat from CWD-infected deer are at risk to prion exposure.
*** now, let’s see what the authors said about this casual link, personal communications years ago, and then the latest on the zoonotic potential from CWD to humans from the TOKYO PRION 2016 CONFERENCE.
see where it is stated NO STRONG evidence. so, does this mean there IS casual evidence ???? “Our conclusion stating that we found no strong evidence of CWD transmission to humans”
From: TSS (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.
snip...
*** twenty-seven CJD patients who regularly consumed venison were reported to the Surveillance Center***,
snip... full text ;
> However, to date, no CWD infections have been reported in people.
sporadic, spontaneous CJD, 85%+ of all human TSE, just not just happen. never in scientific literature has this been proven.
if one looks up the word sporadic or spontaneous at pubmed, you will get a laundry list of disease that are classified in such a way;
sporadic = 54,983 hits https://www.ncbi.nlm.nih.gov/pubmed/?term=sporadic
spontaneous = 325,650 hits https://www.ncbi.nlm.nih.gov/pubmed/?term=spontaneous
key word here is 'reported'. science has shown that CWD in humans will look like sporadic CJD. SO, how can one assume that CWD has not already transmitted to humans? they can't, and it's as simple as that. from all recorded science to date, CWD has already transmitted to humans, and it's being misdiagnosed as sporadic CJD. ...terry
*** LOOKING FOR CWD IN HUMANS AS nvCJD or as an ATYPICAL CJD, LOOKING IN ALL THE WRONG PLACES $$$ ***
*** 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).***
MONDAY, FEBRUARY 25, 2019
MAD DOGS AND ENGLISHMEN BSE, SCRAPIE, CWD, CJD, TSE PRION A REVIEW 2019
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.
==============
***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.
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, J uan-Carlos Espinosa a. Vincent Beringue c. Patricia Aguilar a,
Natalia Fernandez-Borges a. and Alba Marin-Moreno a
"Centro de Investigacion en Sanidad Animal ( CISA-INIA ).. Valdeolmos, Madrid. Spain; b UMR INRA -ENVT 1225 Interactions Holes Agents Pathogenes. ENVT. Toulouse. France: "UR892. Virologie lmmunologie MolécuIaires, Jouy-en-Josas. France
Dietary exposure to bovine spongiform encephalopathy (BSE) contaminated bovine tissues is considered as the origin of variant Creutzfeldt Jakob (vCJD) disease in human. To date, BSE agent is the only recognized zoonotic prion... Despite the variety of Transmissible Spongiform Encephalopathy (TSE) agents that have been circulating for centuries in farmed ruminants there is no apparent epidemiological link between exposure to ruminant products and the occurrence of other form of TSE in human like sporadic Creutzfeldt Jakob Disease (sCJD). However, the zoonotic potential of the diversity of circulating TSE agents has never been systematically assessed.. The major issue in experimental assessment of TSEs zoonotic potential lies in the modeling of the ‘species barrier‘, the biological phenomenon that limits TSE agents’ propagation from a species to another. In the last decade, mice genetically engineered to express normal forms of the human prion protein has proved essential in studying human prions pathogenesis and modeling the capacity of TSEs to cross the human species barrier.
To assess the zoonotic potential of prions circulating in farmed ruminants, we study their transmission ability in transgenic mice expressing human PrPC (HuPrP-Tg). Two lines of mice expressing different forms of the human PrPC (129Met or 129Val) are used to determine the role of the Met129Val dimorphism in susceptibility/resistance to the different agents.
These transmission experiments confirm the ability of BSE prions to propagate in 129M- HuPrP-Tg mice and demonstrate that Met129 homozygotes may be susceptible to BSE in sheep or goat to a greater degree than the BSE agent in cattle and that these agents can convey molecular properties and neuropathological indistinguishable from vCJD. However homozygous 129V mice are resistant to all tested BSE derived prions independently of the originating species suggesting a higher transmission barrier for 129V-PrP variant.
Transmission data also revealed that several scrapie prions propagate in HuPrP-Tg mice with efficiency comparable to that of cattle BSE. While the efficiency of transmission at primary passage was low, subsequent passages resulted in a highly virulent prion disease in both Met129 and Val129 mice.
Transmission of the different scrapie isolates in these mice leads to the emergence of prion strain phenotypes that showed similar characteristics to those displayed by MM1 or VV2 sCJD prion.
These results demonstrate that scrapie prions have a zoonotic potential and raise new questions about the possible link between animal and human prions.
***> 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.
***> 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. <***
Transmission of scrapie prions to primate after an extended silent incubation period
Emmanuel E. Comoy, Jacqueline Mikol, Sophie Luccantoni-Freire, Evelyne Correia, Nathalie Lescoutra-Etchegaray, Valérie Durand, Capucine Dehen, Olivier Andreoletti, Cristina Casalone, Juergen A. Richt, Justin J. Greenlee, Thierry Baron, Sylvie L. Benestad, Paul Brown & Jean-Philippe Deslys Scientific Reports volume 5, Article number: 11573 (2015) | Download Citation
Abstract
Classical bovine spongiform encephalopathy (c-BSE) is the only animal prion disease reputed to be zoonotic, causing variant Creutzfeldt-Jakob disease (vCJD) in humans and having guided protective measures for animal and human health against animal prion diseases. Recently, partial transmissions to humanized mice showed that the zoonotic potential of scrapie might be similar to c-BSE. We here report the direct transmission of a natural classical scrapie isolate to cynomolgus macaque, a highly relevant model for human prion diseases, after a 10-year silent incubation period, with features similar to those reported for human cases of sporadic CJD. Scrapie is thus actually transmissible to primates with incubation periods compatible with their life expectancy, although fourfold longer than BSE. Long-term experimental transmission studies are necessary to better assess the zoonotic potential of other prion diseases with high prevalence, notably Chronic Wasting Disease of deer and elk and atypical/Nor98 scrapie.
SNIP...
Discussion We describe the transmission of spongiform encephalopathy in a non-human primate inoculated 10 years earlier with a strain of sheep c-scrapie. Because of this extended incubation period in a facility in which other prion diseases are under study, we are obliged to consider two alternative possibilities that might explain its occurrence. We first considered the possibility of a sporadic origin (like CJD in humans). Such an event is extremely improbable because the inoculated animal was 14 years old when the clinical signs appeared, i.e. about 40% through the expected natural lifetime of this species, compared to a peak age incidence of 60–65 years in human sporadic CJD, or about 80% through their expected lifetimes. 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.
The second possibility is a laboratory cross-contamination. Three facts make this possibility equally unlikely. First, handling of specimens in our laboratory is performed with fastidious attention to the avoidance of any such cross-contamination. Second, no laboratory cross-contamination has ever been documented in other primate laboratories, including the NIH, even between infected and uninfected animals housed in the same or adjacent cages with daily intimate contact (P. Brown, personal communication). Third, the cerebral lesion profile is different from all the other prion diseases we have studied in this model19, with a correlation between cerebellar lesions (massive spongiform change of Purkinje cells, intense PrPres staining and reactive gliosis26) and ataxia. The iron deposits present in the globus pallidus are a non specific finding that have been reported previously in neurodegenerative diseases and aging27. Conversely, the thalamic lesion was reminiscent of a metabolic disease due to thiamine deficiency28 but blood thiamine levels were within normal limits (data not shown). The preferential distribution of spongiform change in cortex associated with a limited distribution in the brainstem is reminiscent of the lesion profile in MM2c and VV1 sCJD patients29, but interspecies comparison of lesion profiles should be interpreted with caution. It is of note that the same classical scrapie isolate induced TSE in C57Bl/6 mice with similar incubation periods and lesional profiles as a sample derived from a MM1 sCJD patient30.
We are therefore confident that the illness in this cynomolgus macaque represents a true transmission of a sheep c-scrapie isolate directly to an old-world monkey, which taxonomically resides in the primate subdivision (parvorder of catarrhini) that includes humans. With an homology of its PrP protein with humans of 96.4%31, cynomolgus macaque constitutes a highly relevant model for assessing zoonotic risk of prion diseases. Since our initial aim was to show the absence of transmission of scrapie to macaques in the worst-case scenario, we obtained materials from a flock of naturally-infected sheep, affecting animals with different genotypes32. This c-scrapie isolate exhibited complete transmission in ARQ/ARQ sheep (332 ± 56 days) and Tg338 transgenic mice expressing ovine VRQ/VRQ prion protein (220 ± 5 days) (O. Andreoletti, personal communication). From the standpoint of zoonotic risk, it is important to note that sheep with c-scrapie (including the isolate used in our study) have demonstrable infectivity throughout their lymphoreticular system early in the incubation period of the disease (3 months-old for all the lymphoid organs, and as early as 2 months-old in gut-associated lymph nodes)33. In addition, scrapie infectivity has been identified in blood34, milk35 and skeletal muscle36 from asymptomatic but scrapie infected small ruminants which implies a potential dietary exposure for consumers.
Two earlier studies have reported the occurrence of clinical TSE in cynomolgus macaques after exposures to scrapie isolates. In the first study, the “Compton” scrapie isolate (derived from an English sheep) and serially propagated for 9 passages in goats did not transmit TSE in cynomolgus macaque, rhesus macaque or chimpanzee within 7 years following intracerebral challenge1; conversely, after 8 supplementary passages in conventional mice, this “Compton” isolate induced TSE in a cynomolgus macaque 5 years after intracerebral challenge, but rhesus macaques and chimpanzee remained asymptomatic 8.5 years post-exposure8. However, multiple successive passages that are classically used to select laboratory-adapted prion strains can significantly modify the initial properties of a scrapie isolate, thus questioning the relevance of zoonotic potential for the initial sheep-derived isolate. The same isolate had also induced disease into squirrel monkeys (new-world monkey)9. A second historical observation reported that a cynomolgus macaque developed TSE 6 years post-inoculation with brain homogenate from a scrapie-infected Suffolk ewe (derived from USA), whereas a rhesus macaque and a chimpanzee exposed to the same inoculum remained healthy 9 years post-exposure1. This inoculum also induced TSE in squirrel monkeys after 4 passages in mice. Other scrapie transmission attempts in macaque failed but had more shorter periods of observation in comparison to the current study. Further, it is possible that there are differences in the zoonotic potential of different scrapie strains.
The most striking observation in our study is the extended incubation period of scrapie in the macaque model, which has several implications. Firstly, our observations constitute experimental evidence in favor of the zoonotic potential of c-scrapie, at least for this isolate that has been extensively studied32,33,34,35,36. The cross-species zoonotic ability of this isolate should be confirmed by performing duplicate intracerebral exposures and assessing the transmissibility by the oral route (a successful transmission of prion strains through the intracerebral route may not necessarily indicate the potential for oral transmission37). However, such confirmatory experiments may require more than one decade, which is hardly compatible with current general management and support of scientific projects; thus this study should be rather considered as a case report.
Secondly, transmission of c-BSE to primates occurred within 8 years post exposure for the lowest doses able to transmit the disease (the survival period after inoculation is inversely proportional to the initial amount of infectious inoculum). The occurrence of scrapie 10 years after exposure to a high dose (25 mg) of scrapie-infected sheep brain suggests that the macaque has a higher species barrier for sheep c-scrapie than c-BSE, although it is notable that previous studies based on in vitro conversion of PrP suggested that BSE and scrapie prions would have a similar conversion potential for human PrP38.
Thirdly, prion diseases typically have longer incubation periods after oral exposure than after intracerebral inoculations: since humans can develop Kuru 47 years after oral exposure39, an incubation time of several decades after oral exposure to scrapie would therefore be expected, leading the disease to occur in older adults, i.e. the peak age for cases considered to be sporadic disease, and making a distinction between scrapie-associated and truly sporadic disease extremely difficult to appreciate.
Fourthly, epidemiologic evidence is necessary to confirm the zoonotic potential of an animal disease suggested by experimental studies. A relatively short incubation period and a peculiar epidemiological situation (e.g., all the first vCJD cases occurring in the country with the most important ongoing c-BSE epizootic) led to a high degree of suspicion that c-BSE was the cause of vCJD. Sporadic CJD are considered spontaneous diseases with an almost stable and constant worldwide prevalence (0.5–2 cases per million inhabitants per year), and previous epidemiological studies were unable to draw a link between sCJD and classical scrapie6,7,40,41, even though external causes were hypothesized to explain the occurrence of some sCJD clusters42,43,44. However, extended incubation periods exceeding several decades would impair the predictive values of epidemiological surveillance for prion diseases, already weakened by a limited prevalence of prion diseases and the multiplicity of isolates gathered under the phenotypes of “scrapie” and “sporadic CJD”.
Fifthly, considering this 10 year-long incubation period, together with both laboratory and epidemiological evidence of decade or longer intervals between infection and clinical onset of disease, no premature conclusions should be drawn from negative transmission studies in cynomolgus macaques with less than a decade of observation, as in the aforementioned historical transmission studies of scrapie to primates1,8,9. Our observations and those of others45,46 to date are unable to provide definitive evidence regarding the zoonotic potential of CWD, atypical/Nor98 scrapie or H-type BSE. The extended incubation period of the scrapie-affected macaque in the current study also underscores the limitations of rodent models expressing human PrP for assessing the zoonotic potential of some prion diseases since their lifespan remains limited to approximately two years21,47,48. This point is illustrated by the fact that the recently reported transmission of scrapie to humanized mice was not associated with clinical signs for up to 750 days and occurred in an extreme minority of mice with only a marginal increase in attack rate upon second passage13. The low attack rate in these studies is certainly linked to the limited lifespan of mice compared to the very long periods of observation necessary to demonstrate the development of scrapie. Alternatively, one could estimate that a successful second passage is the result of strain adaptation to the species barrier, thus poorly relevant of the real zoonotic potential of the original scrapie isolate of sheep origin49. The development of scrapie in this primate after an incubation period compatible with its lifespan complements the study conducted in transgenic (humanized) mice; taken together these studies suggest that some isolates of sheep scrapie can promote misfolding of the human prion protein and that scrapie can develop within the lifespan of some primate species.
In addition to previous studies on scrapie transmission to primate1,8,9 and the recently published study on transgenic humanized mice13, our results constitute new evidence for recommending that the potential risk of scrapie for human health should not be dismissed. Indeed, human PrP transgenic mice and primates are the most relevant models for investigating the human transmission barrier. To what extent such models are informative for measuring the zoonotic potential of an animal TSE under field exposure conditions is unknown. During the past decades, many protective measures have been successfully implemented to protect cattle from the spread of c-BSE, and some of these measures have been extended to sheep and goats to protect from scrapie according to the principle of precaution. Since cases of c-BSE have greatly reduced in number, those protective measures are currently being challenged and relaxed in the absence of other known zoonotic animal prion disease. We recommend that risk managers should be aware of the long term potential risk to human health of at least certain scrapie isolates, notably for lymphotropic strains like the classical scrapie strain used in the current study. Relatively high amounts of infectivity in peripheral lymphoid organs in animals infected with these strains could lead to contamination of food products produced for human consumption. Efforts should also be maintained to further assess the zoonotic potential of other animal prion strains in long-term studies, notably lymphotropic strains with high prevalence like CWD, which is spreading across North America, and atypical/Nor98 scrapie (Nor98)50 that was first detected in the past two decades and now represents approximately half of all reported cases of prion diseases in small ruminants worldwide, including territories previously considered as scrapie free... Even if the prevailing view is that sporadic CJD is due to the spontaneous formation of CJD prions, it remains possible that its apparent sporadic nature may, at least in part, result from our limited capacity to identify an environmental origin.
U.S.A. 50 STATE BSE MAD COW CONFERENCE CALL Jan. 9, 2001
Subject: BSE--U.S. 50 STATE CONFERENCE CALL Jan. 9, 2001
Date: Tue, 9 Jan 2001 16:49:00 -0800
From: "Terry S. Singeltary Sr."
Reply-To: Bovine Spongiform Encephalopathy
snip...
[host Richard Barns] and now a question from Terry S. Singeltary of CJD Watch.
[TSS] yes, thank you, U.S. cattle, what kind of guarantee can you give for serum or tissue donor herds?
[no answer, you could hear in the back ground, mumbling and 'we can't. have him ask the question again.]
[host Richard] could you repeat the question?
[TSS] U.S. cattle, what kind of guarantee can you give for serum or tissue donor herds?
[not sure whom ask this] what group are you with?
[TSS] CJD Watch, my Mom died from hvCJD and we are tracking CJD world-wide.
[not sure who is speaking] could you please disconnect Mr. Singeltary
[TSS] you are not going to answer my question?
[not sure whom speaking] NO
snip...see full archive and more of this;
THURSDAY, SEPTEMBER 26, 2019
Veterinary Biologics Guideline 3.32E: Guideline for minimising the risk of introducing transmissible spongiform encephalopathy prions and other infectious agents through veterinary biologics
Tuesday, September 10, 2019
FSIS [Docket No. FSIS–2019–0021] Notice of Request To Renew an Approved Information Collection: Specified Risk Materials Singeltary Submission
IBNC BSE TSE Prion mad cow disease
***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 Terry S. Singeltary Sr. on 03 Jul 2015 at 16:53 GMT
Terry S. Singeltary Sr.
*** Singeltary reply ; Molecular, Biochemical and Genetic Characteristics of BSE in Canada Singeltary reply
America BSE 589.2001 FEED REGULATIONS, BSE SURVEILLANCE, BSE TESTING, and CJD TSE Prion
***> cattle, pigs, sheep, cwd, tse, prion, oh my!
***> In contrast, cattle are highly susceptible to white-tailed deer CWD and mule deer CWD in experimental conditions but no natural CWD infections in cattle have been reported (Sigurdson, 2008; Hamir et al., 2006).
Sheep and cattle may be exposed to CWD via common grazing areas with affected deer but so far, appear to be poorly susceptible to mule deer CWD (Sigurdson, 2008). In contrast, cattle are highly susceptible to white-tailed deer CWD and mule deer CWD in experimental conditions but no natural CWD infections in cattle have been reported (Sigurdson, 2008; Hamir et al., 2006). It is not known how susceptible humans are to CWD but given that the prion can be present in muscle, it is likely that humans have been exposed to the agent via consumption of venison (Sigurdson, 2008). Initial experimental research suggests that human susceptibility to CWD is low and there may be a robust species barrier for CWD transmission to humans (Sigurdson, 2008), however the risk appetite for a public health threat may still find this level unacceptable.
cwd scrapie pigs oral routes
***> However, at 51 months of incubation or greater, 5 animals were positive by one or more diagnostic methods. Furthermore, positive bioassay results were obtained from all inoculated groups (oral and intracranial; market weight and end of study) suggesting that swine are potential hosts for the agent of scrapie. <***
>*** Although the current U.S. feed ban is based on keeping tissues from TSE infected cattle from contaminating animal feed, swine rations in the U.S. could contain animal derived components including materials from scrapie infected sheep and goats. These results indicating the susceptibility of pigs to sheep scrapie, coupled with the limitations of the current feed ban, indicates that a revision of the feed ban may be necessary to protect swine production and potentially human health. <***
***> Results: PrPSc was not detected by EIA and IHC in any RPLNs. All tonsils and MLNs were negative by IHC, though the MLN from one pig in the oral <6 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.
Friday, December 14, 2012
DEFRA U.K. What is the risk of Chronic Wasting Disease CWD being introduced into Great Britain? A Qualitative Risk Assessment October 2012
snip.....
In the USA, under the Food and Drug Administration's BSE Feed Regulation (21 CFR 589.2000) most material (exceptions include milk, tallow, and gelatin) from deer and elk is prohibited for use in feed for ruminant animals. With regards to feed for non-ruminant animals, under FDA law, CWD positive deer may not be used for any animal feed or feed ingredients. For elk and deer considered at high risk for CWD, the FDA recommends that these animals do not enter the animal feed system. However, this recommendation is guidance and not a requirement by law. Animals considered at high risk for CWD include:
1) animals from areas declared to be endemic for CWD and/or to be CWD eradication zones and
2) deer and elk that at some time during the 60-month period prior to slaughter were in a captive herd that contained a CWD-positive animal.
Therefore, in the USA, materials from cervids other than CWD positive animals may be used in animal feed and feed ingredients for non-ruminants.
The amount of animal PAP that is of deer and/or elk origin imported from the USA to GB can not be determined, however, as it is not specified in TRACES.
It may constitute a small percentage of the 8412 kilos of non-fish origin processed animal proteins that were imported from US into GB in 2011.
Overall, therefore, it is considered there is a __greater than negligible risk___ that (nonruminant) animal feed and pet food containing deer and/or elk protein is imported into GB.
There is uncertainty associated with this estimate given the lack of data on the amount of deer and/or elk protein possibly being imported in these products.
snip.....
36% in 2007 (Almberg et al., 2011). In such areas, population declines of deer of up to 30 to 50% have been observed (Almberg et al., 2011). In areas of Colorado, the prevalence can be as high as 30% (EFSA, 2011). The clinical signs of CWD in affected adults are weight loss and behavioural changes that can span weeks or months (Williams, 2005). In addition, signs might include excessive salivation, behavioural alterations including a fixed stare and changes in interaction with other animals in the herd, and an altered stance (Williams, 2005). These signs are indistinguishable from cervids experimentally infected with bovine spongiform encephalopathy (BSE). Given this, if CWD was to be introduced into countries with BSE such as GB, for example, infected deer populations would need to be tested to differentiate if they were infected with CWD or BSE to minimise the risk of BSE entering the human food-chain via affected venison. snip..... The rate of transmission of CWD has been reported to be as high as 30% and can approach 100% among captive animals in endemic areas (Safar et al., 2008).
snip.....
In summary, in endemic areas, there is a medium probability that the soil and surrounding environment is contaminated with CWD prions and in a bioavailable form. In rural areas where CWD has not been reported and deer are present, there is a greater than negligible risk the soil is contaminated with CWD prion. snip..... In summary, given the volume of tourists, hunters and servicemen moving between GB and North America, the probability of at least one person travelling to/from a CWD affected area and, in doing so, contaminating their clothing, footwear and/or equipment prior to arriving in GB is greater than negligible... For deer hunters, specifically, the risk is likely to be greater given the increased contact with deer and their environment. However, there is significant uncertainty associated with these estimates.
snip.....
Therefore, it is considered that farmed and park deer may have a higher probability of exposure to CWD transferred to the environment than wild deer given the restricted habitat range and higher frequency of contact with tourists and returning GB residents.
snip.....
***> READ THIS VERY, VERY, CAREFULLY, AUGUST 1997 MAD COW FEED BAN WAS A SHAM, AS I HAVE STATED SINCE 1997! 3 FAILSAFES THE FDA ET AL PREACHED AS IF IT WERE THE GOSPEL, IN TERMS OF MAD COW BSE DISEASE IN USA, AND WHY IT IS/WAS/NOT A PROBLEM FOR THE USA, and those are;
BSE TESTING (failed terribly and proven to be a sham)
BSE SURVEILLANCE (failed terribly and proven to be a sham)
BSE 589.2001 FEED REGULATIONS (another colossal failure, and proven to be a sham)
these are facts folks. trump et al just admitted it with the feed ban.
see;
FDA Reports on VFD Compliance
John Maday
August 30, 2019 09:46 AM VFD-Form 007 (640x427)
Before and after the current Veterinary Feed Directive rules took full effect in January, 2017, the FDA focused primarily on education and outreach. ( John Maday ) Before and after the current Veterinary Feed Directive (VFD) rules took full effect in January, 2017, the FDA focused primarily on education and outreach to help feed mills, veterinarians and producers understand and comply with the requirements. Since then, FDA has gradually increased the number of VFD inspections and initiated enforcement actions when necessary. On August 29, FDA released its first report on inspection and compliance activities. The report, titled “Summary Assessment of Veterinary Feed Directive Compliance Activities Conducted in Fiscal Years 2016 – 2018,” is available online.
SUNDAY, SEPTEMBER 1, 2019
***> FDA Reports on VFD Compliance
TUESDAY, APRIL 18, 2017
*** EXTREME USA FDA PART 589 TSE PRION FEED LOOP HOLE STILL EXIST, AND PRICE OF POKER GOES UP ***
FRIDAY, OCTOBER 25, 2019
Experts testify United States is underprepared for bioterrorism threats Transmissible Spongiform Encephalopathy TSE Prion disease
TUESDAY, OCTOBER 29, 2019
USDA Abruptly Halts Animal ID Plan As Experts Testify USA Underprepared For Bioterrorism Threats Such As BSE TSE Prion aka Mad Cow Disease
FRIDAY, OCTOBER 25, 2019
Presidential Executive Order 13895 of October 22, 2019 President's Council of Advisors on Science and Technology Dumbing Down Sound Science BSE TSE Prion Stacking the deck$$$
THURSDAY, SEPTEMBER 26, 2019
USDA Scientific Integrity Policy Departmental Regulation 1074-001 Breached
MONDAY, OCTOBER 21, 2019
Departmental Freedom of Information Act Regulations FOIA Dumbing Down of America Under the Trump Regime
MONDAY, MAY 20, 2019
Tracking and clarifying differential traits of classical- and atypical L-type bovine spongiform encephalopathy prions after transmission from cattle to cynomolgus monkeys
SUNDAY, APRIL 14, 2019
Estimation of prion infectivity in tissues of cattle infected with atypical BSE by real time-quaking induced conversion assay
WEDNESDAY, APRIL 24, 2019
USDA Announces Atypical Bovine Spongiform Encephalopathy Detection Aug 29, 2018 A Review of Science 2019
WEDNESDAY, JULY 31, 2019
The agent of transmissible mink encephalopathy passaged in sheep is similar to BSE-L
TUESDAY, MARCH 26, 2019
Joint Statement from President Donald J. Trump USA and President Jair Bolsonaro Brazil FOREIGN POLICY BSE TSE Prion aka mad cow disease
SATURDAY, JUNE 01, 2019
Brazil reports another cases of mad cow disease atypical BSE TSE Prion
PLEASE BE ADVISED THERE IS NO SCIENTIFIC PROOF THAT ANY ATYPICAL BSE TSE PRION IS OF A SPONTANEOUS OLD AGE DISEASE, NOT CAUSED BY FEED, THIS IS FALSE AND UNPROVEN, IN FACT, ATYPICAL BSE OF THE L AND H TYPE ARE TRANSMISSIBLE BY ORAL ROUTE. THIS STATEMENT THAT ATYPICAL BSE IS A SPONTANEOUS EVENT CAUSED BY OLD AGE, CAUSED BY NOTHING, IS ABSOLUTELY A LIE, AND THE GOVERNMENT OF BRAZIL, AND OTHER GOVERNMENTS THAT PRODUCE SUCH STATEMENTS, KNOWS THIS IS AN UNPROVEN STATEMENT...TERRY SINGELTARY SR.
TUESDAY, OCTOBER 29, 2019
USDA Abruptly Halts Animal ID Plan As Experts Testify USA Underprepared For Bioterrorism Threats Such As BSE TSE Prion aka Mad Cow Disease
FRIDAY, OCTOBER 11, 2019
CattleTrace to Host First-Ever Industry Symposium
TUESDAY, MARCH 26, 2019
USDA ARS 2018 USAHA RESOLUTIONS TWO PRONGED APPROACH NEEDED FOR ADVANCING CATTLE TRACEABILITY
RESOLUTION NUMBER: 34 APPROVED
SOURCE: COMMITTEE ON CATTLE AND BISON
THURSDAY, AUGUST 08, 2019
Raccoons accumulate PrPSc after intracranial inoculation with the agents of chronic wasting disease (CWD) or transmissible mink encephalopathy (TME) but not atypical scrapie
WEDNESDAY, OCTOBER 16, 2019
Australia Assessment of bulk wheat from Canada Part B: Animal biosecurity risk advice, CWD TSE Prion concerns are mounting
TEXAS CWD TSE PRION STRAIN UNLIKE ANYTHING EVER SEEN
“Wow,” he said. “Unlike anything we've seen before.”
The prions from the Texas deer were a lot harder to destroy than the ones from the Colorado elk. In fact, the guanidine barely damaged them at all. “We’ve never seen that before in any prion strain, which means that it has a completely different structure than we've ever seen before,” says Zabel. And that suggests that it might be a very different kind of chronic wasting disease. The researchers ran the same test on another Texas deer, with the same results.
snip...
THURSDAY, SEPTEMBER 05, 2019
Unique Profile of The Texas CWD TSE Prion isolates, the TSE Prion CWD, Scrapie, BSE in Livestock, and CJD in Humans
SATURDAY, SEPTEMBER 28, 2019
Texas CWD TSE Prion aka Mad Deer Disease Detected Free Range Mule Deer El Paso 145 Positive To Date
FRIDAY, JANUARY 26, 2018
WISCONSIN REPORTS 588 CWD TSE PRION POSITIVE CASES FOR 2017 WITH 4170 CASES CONFIRMED TO DATE
for those that believe in all things stupid, like ted nugent, and say that cwd is not adversely affecting, look no further than Colorado, here's your sign...
Colorado Chronic Wasting Disease Response Plan December 2018
I. Executive Summary Mule deer, white-tailed deer, elk and moose are highly valued species in North America. Some of Colorado’s herds of these species are increasingly becoming infected with chronic wasting disease (CWD). As of July 2018, at least 31 of Colorado's 54 deer herds (57%), 16 of 43 elk herds (37%), and 2 of 9 moose herds (22%) are known to be infected with CWD. Four of Colorado's 5 largest deer herds and 2 of the state’s 5 largest elk herds are infected. Deer herds tend to be more heavily infected than elk and moose herds living in the same geographic area. Not only are the number of infected herds increasing, the past 15 years of disease trends generally show an increase in the proportion of infected animals within herds as well. Of most concern, greater than a 10-fold increase in CWD prevalence has been estimated in some mule deer herds since the early 2000s; CWD is now adversely affecting the performance of these herds.
snip...
(the map on page 71, cwd marked in red, is shocking...tss)
ORIGIN OF CHRONIC WASTING DISEASE TSE PRION?
COLORADO THE ORIGIN OF CHRONIC WASTING DISEASE CWD TSE PRION?
*** 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.
IN CONFIDENCE, REPORT OF AN UNCONVENTIONAL SLOW VIRUS DISEASE IN ANIMALS IN THE USA 1989
ALSO, one of the most, if not the most top TSE Prion God in Science today is Professor Adriano Aguzzi, and he recently commented on just this, on a cwd post on my facebook page August 20 at 1:44pm, quote;
''it pains me to no end to even contemplate the possibility, but it seems entirely plausible that CWD originated from scientist-made spread of scrapie from sheep to deer in the colorado research facility. If true, a terrible burden for those involved.'' August 20 at 1:44pm ...end
”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 viewed it as a wildlife problem and consequently not their province!” page 26.
WEDNESDAY, NOVEMBER 06, 2019
Michigan Total CWD TSE Prion Positive, Suspect Positive, Deer 136 To Date
THURSDAY, OCTOBER 24, 2019
Pennsylvania NEWLY DETECTED CWD-POSITIVE DEER CAPTIVE-RAISED WILL EXPAND DMA 4 IN 2020
FRIDAY, NOVEMBER 01, 2019
South Dakota Chronic Wasting Disease CWD TSE Prion confirmed in Bennett County
MONDAY, OCTOBER 21, 2019
North Dakota Two mule deer taken in September have tested positive for Chronic Wasting Disease CWD TSE Prion Detected in McKenzie County
WEDNESDAY, OCTOBER 16, 2019
Arkansas Chronic Wasting Disease CWD TSE Prion 619 Positive Cases As Of September 15, 2019
FRIDAY, OCTOBER 11, 2019
Minnesota Officials Burn, Bury, Worry As Chronic Wasting Spreads
MONDAY, NOVEMBER 04, 2019
Minnesota Legislators legislating, or throwing away your money for battling cwd tse prion, State Rep. Steve Green, R-Fosston more money to deer farms for antibiotics?
WEDNESDAY, OCTOBER 16, 2019
Kansas Chronic Wasting Disease CWD TSE Prion Update With 216 cervids Positive To Date
FRIDAY, OCTOBER 25, 2019
Wyoming CWD TSE Prion found in a new deer hunt area in Bighorn Mountains
THURSDAY, OCTOBER 03, 2019
Wyoming CWD TSE Prion found in deer west of Continental Divide
THURSDAY, OCTOBER 03, 2019
Montana Huntley deer tests positive for CWD; new management zone set
THURSDAY, OCTOBER 03, 2019
Tennessee Madison County deer sampled within 10 miles of Crockett and Gibson counties has tested positive for CWD, Declared High Risk
THURSDAY, SEPTEMBER 26, 2019
Sweden The third case of CWD in moose in Arjeplog is now established
FRIDAY, OCTOBER 04, 2019
Indiana CWD TSE Prion Surveillance 2019 and before?
THURSDAY, OCTOBER 03, 2019
ALABAMA PREPARES FOR THE STORM Fall 2019 CWD TSE PRION Public Information Meeting Schedule
THURSDAY, OCTOBER 17, 2019
Europe's uneven laws threaten scavengers and Spread Transmissible Spongiform Encephalopathy TSE Prion
MONDAY, OCTOBER 07, 2019
Chronic Wasting Disease (CWD) and Government Response Congressional Research Service May 17, 2019
WEDNESDAY, OCTOBER 02, 2019
Chronic Wasting Disease In Cervids: Prevalence, Impact And Management Strategies
WEDNESDAY, JUNE 26, 2019
Subcommittee Hearing: Chronic Wasting Disease: The Threats to Wildlife, Public Lands, Hunting, and Health
video
CHRONIC WASTING DISEASE CONGRESS Serial No. 107-117 May 16, 2002
CHRONIC WASTING DISEASE
JOINT OVERSIGHT HEARING BEFORE THE SUBCOMMITTEE ON FORESTS AND FOREST HEALTH JOINT WITH THE SUBCOMMITTEE ON FISHERIES CONSERVATION, WILDLIFE AND OCEANS OF THE COMMITTEE ON RESOURCES U.S. HOUSE OF REPRESENTATIVES ONE HUNDRED SEVENTH CONGRESS SECOND SESSION
May 16, 2002
Serial No. 107-117
snip...
Mr. MCINNIS. Today, this joint Subcommittee hearing will explore an issue of immeasurable importance to the growing number of communities in wide-ranging parts of this country, the growing incidence of Chronic Wasting Disease in North America’s wild and captive deer and elk populations. In a matter of just a few months, this once parochial concern has grown into something much larger and much more insidious than anyone could have imagined or predicted.
As each day passes, this problem grows in its size, scope, and consequence. One thing becomes clear. Chronic Wasting Disease is not a Colorado problem. It is a Wisconsin problem or a Nebraska or Wyoming problem. It is a national problem and anything short of a fully integrated, systematic national assault on this simply will not do, which is precisely why we brought our group together here today.
snip...
So this is a disease that is spreading throughout the continent and it is going to require a national response as well as the efforts that are currently taking place in States like Wisconsin, Colorado, Nebraska, Wyoming, the interest they now have down in Texas and some of the neighboring States that have large white-tailed deer population and also elk.
This is a huge issue for us, Mr. Chairman, in the State of Wisconsin. I want to commend Governor McCallum and your staff and the various agencies for the rapid response that you have shown, given the early detection of CWD after the last deer hunting season. The problem that we have, though, is just a lack of information, good science in regards to what is the best response, how dangerous is this disease. We cannot close the door, quite frankly, with the paucity of scientific research that is out there right now in regards to how the disease spreads, the exposure of other livestock herds—given the importance of our dairy industry in the State, that is a big issue—and also the human health effects.
FRIDAY, OCTOBER 04, 2019
Inactivation of chronic wasting disease prions using sodium hypochlorite
i think some hunters that don't read this carefully are going to think this is a cure all for cwd tse contamination. IT'S NOT!
first off, it would take a strong bleach type sodium hypochlorite, that is NOT your moms bleach she uses in her clothes, and store bought stuff.
Concentrated bleach is an 8.25 percent solution of sodium hypochlorite, up from the “regular bleach” concentration of 5.25 percent.Nov 1, 2013 https://waterandhealth.org/disinfect/high-strength-bleach-2/
second off, the study states plainly;
''We found that a five-minute treatment with a 40% dilution of household bleach was effective at inactivating CWD seeding activity from stainless-steel wires and CWD-infected brain homogenates. However, bleach was not able to inactivate CWD seeding activity from solid tissues in our studies.''
''We initially tested brains from two CWD-infected mice and one uninfected mouse using 40% bleach for 5 minutes. The results from these experiments showed almost no elimination of prion seeding activity (Table 4). We then increased the treatment time to 30 minutes and tested 40% and 100% bleach treatments. Again, the results were disappointing and showed less than a 10-fold decrease in CWD-seeding activity (Table 4). Clearly, bleach is not able to inactivate prions effectively from small brain pieces under the conditions tested here.''
''We found that both the concentration of bleach and the time of treatment are critical for inactivation of CWD prions. A 40% bleach treatment for 5 minutes successfully eliminated detectable prion seeding activity from both CWD-positive brain homogenate and stainless-steel wires bound with CWD. However, even small solid pieces of CWD-infected brain were not successfully decontaminated with the use of bleach.''
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0223659
https://chronic-wasting-disease.blogspot.com/2019/10/inactivation-of-chronic-wasting-disease.html
i think with all the fear from recent studies, and there are many, of potential, or likelihood of zoonosis, if it has not already happened as scjd, i think this study came out to help out on some of that fear, that maybe something will help, but the study plainly states it's for sure not a cure all for exposure and contamination of the cwd tse prion on surface materials. imo...terry
HUNTERS, CWD TSE PRION, THIS SHOULD A WAKE UP CALL TO ALL OF YOU GUTTING AND BONING OUT YOUR KILL IN THE FIELD, AND YOUR TOOLS YOU USE...
* 1: J Neurol Neurosurg Psychiatry 1994 Jun;57(6):757-8
Transmission of Creutzfeldt-Jakob disease to a chimpanzee by electrodes contaminated during neurosurgery.
Gibbs CJ Jr, Asher DM, Kobrine A, Amyx HL, Sulima MP, Gajdusek DC.
Laboratory of Central Nervous System Studies, National Institute of
Neurological Disorders and Stroke, National Institutes of Health,
Bethesda, MD 20892.
Stereotactic multicontact electrodes used to probe the cerebral cortex of a middle aged woman with progressive dementia were previously implicated in the accidental transmission of Creutzfeldt-Jakob disease (CJD) to two younger patients. The diagnoses of CJD have been confirmed for all three cases. More than two years after their last use in humans, after three cleanings and repeated sterilisation in ethanol and formaldehyde vapour, the electrodes were implanted in the cortex of a chimpanzee. Eighteen months later the animal became ill with CJD. This finding serves to re-emphasise the potential danger posed by reuse of instruments contaminated with the agents of spongiform encephalopathies, even after scrupulous attempts to clean them.
PMID: 8006664 [PubMed - indexed for MEDLINE]
Wednesday, September 11, 2019
Is the re-use of sterilized implant abutments safe enough? (Implant abutment safety) iatrogenic TSE Prion
172. Establishment of PrPCWD extraction and detection methods in the farm soil
Kyung Je Park, Hoo Chang Park, In Soon Roh, Hyo Jin Kim, Hae-Eun Kang and Hyun Joo Sohn
Foreign Animal Disease Division, Animal and Plant Quarantine Agency, Gimcheon, Gyeongsangbuk-do, Korea
ABSTRACT
Introduction: Transmissible spongiform encephalopathy (TSE) is a fatal neurodegenerative disorder, which is so-called as prion diseases due to the causative agents (PrPSc). TSEs are believed to be due to the template-directed accumulation of disease-associated prion protein, generally designated PrPSc. Chronic wasting disease (CWD) is the prion disease that is known spread horizontally. CWD has confirmed last in Republic of Korea in 2016 since first outbreak of CWD in 2001. The environmental reservoirs mediate the transmission of this disease. The significant levels of infectivity have been detected in the saliva, urine, and faeces of TSE-infected animals. Soil can serve as a stable reservoir for infectious prion proteins. We found that PrPCWD can be extracted and detected in CWD contaminated soil which has kept at room temperature until 4 years after 0.001 ~ 1% CWD exposure and natural CWD-affected farm soil through PBS washing and sPMCAb.
Materials and Methods: Procedure of serial PMCAb. CWD contaminated soil which has kept at room temperature (RT) for 1 ~ 4 year after 0.001%~1% CWD brain homogenates exposure for 4 months collected 0.14 g. The soil was collected by the same method once of year until 4 year after stop CWD exposure. We had conducted the two steps. There are two kinds of 10 times washing step and one amplification step. The washing step was detached PrPSc from contaminated soil by strong vortex with maximum rpm. We harvest supernatant every time by 10 times. As the other washing step, the Washed soil was made by washing 10 times soil using slow rotator and then harvest resuspended PBS for removing large impurity material. Last step was prion amplification step for detection of PrPCWD in soil supernatant and the washed soil by sPMCAb. Normal brain homogenate (NBH) was prepared by homogenization of brains with glass dounce in 9 volumes of cold PBS with TritonX-100, 5 mM EDTA, 150 mM NaCl and 0.05% Digitonin (sigma) plus Complete mini protease inhibitors (Roche) to a final concentration of 5%(w/v) NBHs were centrifuged at 2000 g for 1 min, and supernatant removed and frozen at −70 C for use. CWD consisted of brain from natural case in Korea and was prepared as 10%(w/v) homogenate. Positive sample was diluted to a final dilution 1:1000 in NBH, with serial 3:7 dilutions in NBH. Sonication was performed with a Misonix 4000 sonicator with amplitude set to level 70, generating an average output of 160W with two teflon beads during each cycle. One round consisted of 56 cycles of 30 s of sonication followed 9 min 30 s of 37°C incubation. Western Blotting (WB) for PrPSc detection. The samples (20 µL) after each round of amplification were mixed with proteinase K (2 mg/ml) and incubated 37°C for 1 h. Samples were separated by SDS-PAGE and transferred onto PVDF membrane. After blocking, the membrane was incubated for 1 h with 1st antibody S1 anti rabbit serum (APQA, 1:3000) and developed with enhanced chemiluminescence detection system.
Results: We excluded from first to third supernatant in view of sample contamination. It was confirmed abnormal PrP amplification in all soil supernatants from fourth to tenth. From 0.01% to 1% contaminated washed soils were identified as abnormal prions. 0.001% contaminated washed soil did not show PrP specific band (Fig 1). The soil was collected by the same method once of year until 4 year after stop CWD exposure. After sPMCAb, there were no PrPCWD band in from second to fourth year 0.001% washed soil. but It was confirmed that the abnormal prion was amplified in the washing supernatant which was not amplified in the washed soil. we have decided to use soil supernatant for soil testing (Fig. 2). After third rounds of amplification, PrPSc signals observed in three out of four sites from CWD positive farm playground. No signals were observed in all soil samples from four CWD negative farm (Fig. 3).
Conclusions: Our studies showed that PrPCWD persist in 0.001% CWD contaminated soil for at least 4 year and natural CWD-affected farm soil. When cervid reintroduced into CWD outbreak farm, the strict decontamination procedures of the infectious agent should be performed in the environment of CWD-affected cervid habitat.
===
186. Serial detection of hematogenous prions in CWD-infected deer
Amy V. Nalls, Erin E. McNulty, Nathaniel D. Denkers, Edward A. Hoover and Candace K. Mathiason
Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, CO, USA
CONTACT Amy V. Nalls amy.nalls@colostate.edu
ABSTRACT
Blood contains the infectious agent associated with prion disease affecting several mammalian species, including humans, cervids, sheep, and cattle. It has been confirmed that sufficient prion agent is present in the blood of both symptomatic and asymptomatic carriers to initiate the amyloid templating and accumulation process that results in this fatal neurodegenerative disease. Yet, to date, the ability to detect blood-borne prions by in vitro methods remains difficult.
We have capitalized on blood samples collected from longitudinal chronic wasting disease (CWD) studies in the native white-tailed deer host to examine hematogenous prion load in blood collected minutes, days, weeks and months post exposure. Our work has focused on refinement of the amplification methods RT-QuIC and PMCA. We demonstrate enhanced in vitro detection of amyloid seeding activity (prions) in blood cell fractions harvested from deer orally-exposed to 300 ng CWD positive brain or saliva.
These findings permit assessment of the role hematogenous prions play in the pathogenesis of CWD and provide tools to assess the same for prion diseases of other mammalian species.
Considering the oral secretion of prions, saliva from CWD-infected deer was shown to transmit disease to other susceptible naïve deer when harvested from the animals in both the
and preclinical stages69
of infection, albeit within relatively large volumes of saliva (50 ml). In sheep with preclinical, natural scrapie infections, sPMCA facilitated the detection of PrPSc within buccal swabs throughout most of the incubation period of the disease with an apparent peak in prion secretion around the mid-term of disease progression.70
The amounts of prion present in saliva are likely to be low as indicated by CWD-infected saliva producing prolonged incubation periods and incomplete attack rates within the transgenic mouse bioassay.41
snip...
Indeed, it has also been shown that the scrapie and CWD prions are excreted in urine, feces and saliva and are likely to be excreted from skin. While levels of prion within these excreta/secreta are very low, they are produced throughout long periods of preclinical disease as well as clinical disease. Furthermore, the levels of prion in such materials are likely to be increased by concurrent inflammatory conditions affecting the relevant secretory organ or site. Such dissemination of prion into the environment is very likely to facilitate the repeat exposure of flockmates to low levels of the disease agent, possibly over years.
snip...
Given the results with scrapie-contaminated milk and CWD-contaminated saliva, it seems very likely that these low levels of prion in different secreta/excreta are capable of transmitting disease upon prolonged exposure, either through direct animal-to-animal contact or through environmental reservoirs of infectivity.
the other part, these tissues and things in the body then shed or secrete prions which then are the route to other animals into the environment, so in particular, the things, the secretions that are infectious are salvia, feces, blood and urine. so pretty much anything that comes out of a deer is going to be infectious and potential for transmitting disease.
***>>> 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.
HUNTERS, CWD TSE PRION, THIS SHOULD A WAKE UP CALL TO ALL OF YOU GUTTING AND BONING OUT YOUR KILL IN THE FIELD, AND YOUR TOOLS YOU USE...
* 1: J Neurol Neurosurg Psychiatry 1994 Jun;57(6):757-8
Transmission of Creutzfeldt-Jakob disease to a chimpanzee by electrodes contaminated during neurosurgery.
Gibbs CJ Jr, Asher DM, Kobrine A, Amyx HL, Sulima MP, Gajdusek DC.
Laboratory of Central Nervous System Studies, National Institute of
Neurological Disorders and Stroke, National Institutes of Health,
Bethesda, MD 20892.
Stereotactic multicontact electrodes used to probe the cerebral cortex of a middle aged woman with progressive dementia were previously implicated in the accidental transmission of Creutzfeldt-Jakob disease (CJD) to two younger patients. The diagnoses of CJD have been confirmed for all three cases. More than two years after their last use in humans, after three cleanings and repeated sterilisation in ethanol and formaldehyde vapour, the electrodes were implanted in the cortex of a chimpanzee. Eighteen months later the animal became ill with CJD. This finding serves to re-emphasise the potential danger posed by reuse of instruments contaminated with the agents of spongiform encephalopathies, even after scrupulous attempts to clean them.
PMID: 8006664 [PubMed - indexed for MEDLINE]
Wednesday, September 11, 2019
Is the re-use of sterilized implant abutments safe enough? (Implant abutment safety) iatrogenic TSE Prion
SATURDAY, MARCH 16, 2019
Medical Devices Containing Materials Derived from Animal Sources (Except for In Vitro Diagnostic Devices) Guidance for Industry and Food and Drug Administration Staff Document issued on March 15, 2019 Singeltary Submission
THURSDAY, SEPTEMBER 27, 2018
***> Estimating the impact on food and edible materials of changing scrapie control measures: The scrapie control model
THE tse prion aka mad cow type disease is not your normal pathogen.
The TSE prion disease survives ashing to 600 degrees celsius, that’s around 1112 degrees farenheit.
you cannot cook the TSE prion disease out of meat.
you can take the ash and mix it with saline and inject that ash into a mouse, and the mouse will go down with TSE.
Prion Infected Meat-and-Bone Meal Is Still Infectious after Biodiesel Production as well.
the TSE prion agent also survives Simulated Wastewater Treatment Processes.
IN fact, you should also know that the TSE Prion agent will survive in the environment for years, if not decades.
you can bury it and it will not go away.
The TSE agent is capable of infected your water table i.e. Detection of protease-resistant cervid prion protein in water from a CWD-endemic area.
it’s not your ordinary pathogen you can just cook it out and be done with.
***> that’s what’s so worrisome about Iatrogenic mode of transmission, a simple autoclave will not kill this TSE prion agent.
1: J Neurol Neurosurg Psychiatry 1994 Jun;57(6):757-8
***> Transmission of Creutzfeldt-Jakob disease to a chimpanzee by electrodes contaminated during neurosurgery.
Gibbs CJ Jr, Asher DM, Kobrine A, Amyx HL, Sulima MP, Gajdusek DC.
Laboratory of Central Nervous System Studies, National Institute of
Neurological Disorders and Stroke, National Institutes of Health,
Bethesda, MD 20892.
Stereotactic multicontact electrodes used to probe the cerebral cortex of a middle aged woman with progressive dementia were previously implicated in the accidental transmission of Creutzfeldt-Jakob disease (CJD) to two younger patients. The diagnoses of CJD have been confirmed for all three cases. More than two years after their last use in humans, after three cleanings and repeated sterilisation in ethanol and formaldehyde vapour, the electrodes were implanted in the cortex of a chimpanzee. Eighteen months later the animal became ill with CJD. This finding serves to re-emphasise the potential danger posed by reuse of instruments contaminated with the agents of spongiform encephalopathies, even after scrupulous attempts to clean them.
PMID: 8006664 [PubMed - indexed for MEDLINE]
2018 - 2019
***> This is very likely to have parallels with control efforts for CWD in cervids.
Rapid recontamination of a farm building occurs after attempted prion removal
Kevin Christopher Gough, BSc (Hons), PhD1, Claire Alison Baker, BSc (Hons)2, Steve Hawkins, MIBiol3, Hugh Simmons, BVSc, MRCVS, MBA, MA3, Timm Konold, DrMedVet, PhD, MRCVS3 and Ben Charles Maddison, BSc (Hons), PhD2
Abstract
The transmissible spongiform encephalopathy scrapie of sheep/goats and chronic wasting disease of cervids are associated with environmental reservoirs of infectivity.
Preventing environmental prions acting as a source of infectivity to healthy animals is of major concern to farms that have had outbreaks of scrapie and also to the health management of wild and farmed cervids.
Here, an efficient scrapie decontamination protocol was applied to a farm with high levels of environmental contamination with the scrapie agent.
Post-decontamination, no prion material was detected within samples taken from the farm buildings as determined using a sensitive in vitro replication assay (sPMCA).
A bioassay consisting of 25 newborn lambs of highly susceptible prion protein genotype VRQ/VRQ introduced into this decontaminated barn was carried out in addition to sampling and analysis of dust samples that were collected during the bioassay.
Twenty-four of the animals examined by immunohistochemical analysis of lymphatic tissues were scrapie-positive during the bioassay, samples of dust collected within the barn were positive by month 3.
The data illustrates the difficulty in decontaminating farm buildings from scrapie, and demonstrates the likely contribution of farm dust to the recontamination of these environments to levels that are capable of causing disease.
snip...
As in the authors' previous study,12 the decontamination of this sheep barn was not effective at removing scrapie infectivity, and despite the extra measures brought into this study (more effective chemical treatment and removal of sources of dust) the overall rates of disease transmission mirror previous results on this farm. With such apparently effective decontamination (assuming that at least some sPMCA seeding ability is coincident with infectivity), how was infectivity able to persist within the environment and where does infectivity reside? Dust samples were collected in both the bioassay barn and also a barn subject to the same decontamination regime within the same farm (but remaining unoccupied). Within both of these barns dust had accumulated for three months that was able to seed sPMCA, indicating the accumulation of scrapie-containing material that was independent of the presence of sheep that may have been incubating and possibly shedding low amounts of infectivity.
This study clearly demonstrates the difficulty in removing scrapie infectivity from the farm environment. Practical and effective prion decontamination methods are still urgently required for decontamination of scrapie infectivity from farms that have had cases of scrapie and this is particularly relevant for scrapiepositive goatherds, which currently have limited genetic resistance to scrapie within commercial breeds.24 This is very likely to have parallels with control efforts for CWD in cervids.
Acknowledgements The authors thank the APHA farm staff, Tony Duarte, Olly Roberts and Margaret Newlands for preparation of the sheep pens and animal husbandry during the study. The authors also thank the APHA pathology team for RAMALT and postmortem examination.
Funding This study was funded by DEFRA within project SE1865.
Competing interests None declared.
Saturday, January 5, 2019
Rapid recontamination of a farm building occurs after attempted prion removal
THURSDAY, FEBRUARY 28, 2019
BSE infectivity survives burial for five years with only limited spread
***> CONGRESSIONAL ABSTRACTS PRION CONFERENCE 2018
P69 Experimental transmission of CWD from white-tailed deer to co-housed reindeer
Mitchell G (1), Walther I (1), Staskevicius A (1), Soutyrine A (1), Balachandran A (1)
(1) National & OIE Reference Laboratory for Scrapie and CWD, Canadian Food Inspection Agency, Ottawa, Ontario, Canada.
Chronic wasting disease (CWD) continues to be detected in wild and farmed cervid populations of North America, affecting predominantly white-tailed deer, mule deer and elk. Extensive herds of wild caribou exist in northern regions of Canada, although surveillance has not detected the presence of CWD in this population. Oral experimental transmission has demonstrated that reindeer, a species closely related to caribou, are susceptible to CWD. Recently, CWD was detected for the first time in Europe, in wild Norwegian reindeer, advancing the possibility that caribou in North America could also become infected. Given the potential overlap in habitat between wild CWD-infected cervids and wild caribou herds in Canada, we sought to investigate the horizontal transmissibility of CWD from white-tailed deer to reindeer.
Two white-tailed deer were orally inoculated with a brain homogenate prepared from a farmed Canadian white-tailed deer previously diagnosed with CWD. Two reindeer, with no history of exposure to CWD, were housed in the same enclosure as the white-tailed deer, 3.5 months after the deer were orally inoculated. The white-tailed deer developed clinical signs consistent with CWD beginning at 15.2 and 21 months post-inoculation (mpi), and were euthanized at 18.7 and 23.1 mpi, respectively. Confirmatory testing by immunohistochemistry (IHC) and western blot demonstrated widespread aggregates of pathological prion protein (PrPCWD) in the central nervous system and lymphoid tissues of both inoculated white-tailed deer. Both reindeer were subjected to recto-anal mucosal associated lymphoid tissue (RAMALT) biopsy at 20 months post-exposure (mpe) to the white-tailed deer. The biopsy from one reindeer contained PrPCWD confirmed by IHC. This reindeer displayed only subtle clinical evidence of disease prior to a rapid decline in condition requiring euthanasia at 22.5 mpe. Analysis of tissues from this reindeer by IHC revealed widespread PrPCWD deposition, predominantly in central nervous system and lymphoreticular tissues. Western blot molecular profiles were similar between both orally inoculated white-tailed deer and the CWD positive reindeer. Despite sharing the same enclosure, the other reindeer was RAMALT negative at 20 mpe, and PrPCWD was not detected in brainstem and lymphoid tissues following necropsy at 35 mpe. Sequencing of the prion protein gene from both reindeer revealed differences at several codons, which may have influenced susceptibility to infection.
Natural transmission of CWD occurs relatively efficiently amongst cervids, supporting the expanding geographic distribution of disease and the potential for transmission to previously naive populations. The efficient horizontal transmission of CWD from white-tailed deer to reindeer observed here highlights the potential for reindeer to become infected if exposed to other cervids or environments infected with CWD.
***> Infectious agent of sheep scrapie may persist in the environment for at least 16 years
***> Nine of these recurrences occurred 14–21 years after culling, apparently as the result of environmental contamination, but outside entry could not always be absolutely excluded.
Gudmundur Georgsson,1 Sigurdur Sigurdarson2 and Paul Brown3
Correspondence
Gudmundur Georgsson ggeorgs@hi.is
1 Institute for Experimental Pathology, University of Iceland, Keldur v/vesturlandsveg, IS-112 Reykjavı´k, Iceland
2 Laboratory of the Chief Veterinary Officer, Keldur, Iceland
3 Bethesda, Maryland, USA
Received 7 March 2006 Accepted 6 August 2006
In 1978, a rigorous programme was implemented to stop the spread of, and subsequently eradicate, sheep scrapie in Iceland. Affected flocks were culled, premises were disinfected and, after 2–3 years, restocked with lambs from scrapie-free areas. Between 1978 and 2004, scrapie recurred on 33 farms. Nine of these recurrences occurred 14–21 years after culling, apparently as the result of environmental contamination, but outside entry could not always be absolutely excluded. Of special interest was one farm with a small, completely self-contained flock where scrapie recurred 18 years after culling, 2 years after some lambs had been housed in an old sheephouse that had never been disinfected. Epidemiological investigation established with near certitude that the disease had not been introduced from the outside and it is concluded that the agent may have persisted in the old sheep-house for at least 16 years.
TITLE: PATHOLOGICAL FEATURES OF CHRONIC WASTING DISEASE IN REINDEER AND DEMONSTRATION OF HORIZONTAL TRANSMISSION
*** DECEMBER 2016 CDC EMERGING INFECTIOUS DISEASE JOURNAL CWD HORIZONTAL TRANSMISSION
SEE;
Back around 2000, 2001, or so, I was corresponding with officials abroad during the bse inquiry, passing info back and forth, and some officials from here inside USDA aphis FSIS et al. In fact helped me get into the USA 50 state emergency BSE conference call way back. That one was a doozy. But I always remember what “deep throat” I never knew who they were, but I never forgot;
Some unofficial information from a source on the inside looking out -
Confidential!!!!
As early as 1992-3 there had been long studies conducted on small pastures containing scrapie infected sheep at the sheep research station associated with the Neuropathogenesis Unit in Edinburgh, Scotland. Whether these are documented...I don't know. But personal recounts both heard and recorded in a daily journal indicate that leaving the pastures free and replacing the topsoil completely at least 2 feet of thickness each year for SEVEN years....and then when very clean (proven scrapie free) sheep were placed on these small pastures.... the new sheep also broke out with scrapie and passed it to offspring. I am not sure that TSE contaminated ground could ever be free of the agent!! A very frightening revelation!!!
---end personal email---end...tss
Infectivity surviving ashing to 600*C is (in my opinion) degradable but infective. based on Bown & Gajdusek, (1991), landfill and burial may be assumed to have a reduction factor of 98% (i.e. a factor of 50) over 3 years. CJD-infected brain-tissue remained infectious after storing at room-temperature for 22 months (Tateishi et al, 1988). Scrapie agent is known to remain viable after at least 30 months of desiccation (Wilson et al, 1950). and pastures that had been grazed by scrapie-infected sheep still appeared to be contaminated with scrapie agent three years after they were last occupied by sheep (Palsson, 1979).
Dr. Paul Brown Scrapie Soil Test BSE Inquiry Document
THURSDAY, FEBRUARY 28, 2019
BSE infectivity survives burial for five years with only limited spread
Using in vitro Prion replication for high sensitive detection of prions and prionlike proteins and for understanding mechanisms of transmission.
Claudio Soto Mitchell Center for Alzheimer's diseases and related Brain disorders, Department of Neurology, University of Texas Medical School at Houston.
Prion and prion-like proteins are misfolded protein aggregates with the ability to selfpropagate to spread disease between cells, organs and in some cases across individuals. I n T r a n s m i s s i b l e s p o n g i f o r m encephalopathies (TSEs), prions are mostly composed by a misfolded form of the prion protein (PrPSc), which propagates by transmitting its misfolding to the normal prion protein (PrPC). The availability of a procedure to replicate prions in the laboratory may be important to study the mechanism of prion and prion-like spreading and to develop high sensitive detection of small quantities of misfolded proteins in biological fluids, tissues and environmental samples. Protein Misfolding Cyclic Amplification (PMCA) is a simple, fast and efficient methodology to mimic prion replication in the test tube. PMCA is a platform technology that may enable amplification of any prion-like misfolded protein aggregating through a seeding/nucleation process. In TSEs, PMCA is able to detect the equivalent of one single molecule of infectious PrPSc and propagate prions that maintain high infectivity, strain properties and species specificity. Using PMCA we have been able to detect PrPSc in blood and urine of experimentally infected animals and humans affected by vCJD with high sensitivity and specificity. Recently, we have expanded the principles of PMCA to amplify amyloid-beta (Aβ) and alphasynuclein (α-syn) aggregates implicated in Alzheimer's and Parkinson's diseases, respectively. Experiments are ongoing to study the utility of this technology to detect Aβ and α-syn aggregates in samples of CSF and blood from patients affected by these diseases.
=========================
***>>> Recently, we have been using PMCA to study the role of environmental prion contamination on the horizontal spreading of TSEs. These experiments have focused on the study of the interaction of prions with plants and environmentally relevant surfaces. Our results show that plants (both leaves and roots) bind tightly to prions present in brain extracts and excreta (urine and feces) and retain even small quantities of PrPSc for long periods of time. Strikingly, ingestion of prioncontaminated leaves and roots produced disease with a 100% attack rate and an incubation period not substantially longer than feeding animals directly with scrapie brain homogenate. Furthermore, plants can uptake prions from contaminated soil and transport them to different parts of the plant tissue (stem and leaves). Similarly, prions bind tightly to a variety of environmentally relevant surfaces, including stones, wood, metals, plastic, glass, cement, etc. Prion contaminated surfaces efficiently transmit prion disease when these materials were directly injected into the brain of animals and strikingly when the contaminated surfaces were just placed in the animal cage. These findings demonstrate that environmental materials can efficiently bind infectious prions and act as carriers of infectivity, suggesting that they may play an important role in the horizontal transmission of the disease.
========================
Since its invention 13 years ago, PMCA has helped to answer fundamental questions of prion propagation and has broad applications in research areas including the food industry, blood bank safety and human and veterinary disease diagnosis.
New studies on the heat resistance of hamster-adapted scrapie agent: Threshold survival after ashing at 600°C suggests an inorganic template of replication
Prion Infected Meat-and-Bone Meal Is Still Infectious after Biodiesel Production
Detection of protease-resistant cervid prion protein in water from a CWD-endemic area
A Quantitative Assessment of the Amount of Prion Diverted to Category 1 Materials and Wastewater During Processing
Rapid assessment of bovine spongiform encephalopathy prion inactivation by heat treatment in yellow grease produced in the industrial manufacturing process of meat and bone meals
PPo4-4:
Survival and Limited Spread of TSE Infectivity after Burial
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 ***
WEDNESDAY, MARCH 13, 2019
CWD, TSE, PRION, MATERNAL mother to offspring, testes, epididymis, seminal fluid, and blood
Subject: Prion 2019 Conference
See full Prion 2019 Conference Abstracts
see scientific program and follow the cwd studies here;
Thursday, May 23, 2019
Prion 2019 Emerging Concepts CWD, BSE, SCRAPIE, CJD, SCIENTIFIC PROGRAM Schedule and Abstracts
FRIDAY, MAY 24, 2019
Assessing chronic wasting disease strain differences in free-ranging cervids across the United States
MONDAY, MAY 20, 2019
APHIS, USDA, Announces the Finalized Chronic Wasting Disease Herd Certification Program Standards Singeltary Submissions
SUNDAY, JULY 14, 2019
Korea Chronic Wasting Disease CWD TSE Prion additional cases were observed in red deer, sika deer, and their crossbred deer in 2010 and 2016, beyond that, anyone's guess
Korea Chronic Wasting Disease CWD TSE Prion additional cases were observed in red deer, sika deer, and their crossbred deer in 2010 and 2016
In Korea, CWD was only confirmed in elk in 2001, 2004, and 2005 [13]; however, additional cases were observed in red deer, sika deer, and their crossbred deer in 2010 and 2016 [14]. Therefore, it is important to prevent CWD recurrence in the Republic of Korea, and farmers that have experienced a CWD outbreak are required to disinfect the farm before reintroducing the cervids. Thus, farmers require a disinfectant solution that is marketed and readily available to effectively inactivate prions.
[14] Sohn HJ, Roh IS, Kim HJ, et al. Epidemiology of chronic wasting disease in Korea. Prion. 2106;10 (supp1):S16–S17
WS-03: Epidemiology of chronic wasting disease in Korea
Hyun Joo Sohn
In Soon Roh
Hyo Jin Kim
Tae Young Suh
Kyung Je Park
Hoo Chang Park
Byounghan Kim
Foreign Animal Disease Division (FADD), Animal and Plant Quarantine Agency (QIA), Gimcheon, Korea
Transmissible spongiform encephalopathy (TSE) is a fatal neurodegenerative disorder, which is so-called as prion diseases due to the causative agents (PrPSc). TSEs are believed to be due to the template-directed accumulation of disease-associated prion protein, generally designated PrPSc. Based on export information of Chronic wasting disease (CWD) suspected elk from Canada to Korea, CWD surveilance program was initiated by the Ministry of Agriculture, Food and Rural Affairs (MAFRA) in 2001. CWD control measures included stamping out of all animals in the affected farm, and through cleaning and disinfection of the premises. In addition, nationwide clinical surveillance of Korean native cervid and improved measures to ensure reporting of CWD suspect cases were implemented. Total of 9 elks were found to be affected. CWD was designated as a notifiable disease under the Act for Prevention of Livestock Epidemics in 2002. Additional CWD cases– 12 elks and 2 elks – were diagnosed in 2004 and 2005. On 2010, 6 elks, 7 sika deer, one red deer and 5 cross-breeds were confirmed as positive. Further epidemiological investigations showed that these CWD outbreaks were linked to the importation of elks from Canada in 1994 based on circumstantial evidences. CWD is the prion disease that is known spread horizontally. The experimental studies have shown that PrPCWD is capable of transmitting CWD through saliva and blood. We conducted sPMCA and animal biosassy using contaminated soils in the playground of farm 2 which considered horizontal transmission between cervid and have been confirmed infectious PrPCWD. This result suggests PrPCWD shedding in the CWD contaminated soil is progressive through the disease course.
Keywords: CWD, soil, sPMCA
Additional Cases of Chronic Wasting Disease in Imported Deer in Korea
Tae-Yung KIM1,3), Hyun-Joo SHON2), Yi-Seok JOO2), Un-Kyong MUN2), Kyung-Sun KANG3) and Yong-Soon LEE3)* 1)Animal Health Division, Ministry of Agriculture & Forestry, Kwacheon 427–760, 2)National Veterinary Research & Quarantine Service, Anyang 430–016 and 3)Department of Veterinary Public Health, College of Veterinary Medicine, Seoul National University, Seoul 151– 742, Korea (Received 21 January 2005/Accepted 27 May 2005)
ABSTRACT.
Chronic Wasting Disease (CWD), which had previously occurred only in the U.S.A. and Canada, broke out in a farm at Chungbuk, Korea from imported Canadian deer (Aug. 8, 2001). CWD distribution, through surveillance and epidemiologic investigations, was reported for 93 deer (43 from the CWD originating farm and 50 imported with the CWD originating farm’s deer) out of 144 deer (72 from the CWD originating farm and 72 imported with the CWD originating farm’s deer) that were breeding at 30 different farms. On Oct. 4 and Oct. 8, 2001, additional cases of CWD were investigated. As a result of slaughtering cohabitating deer, it was verified that other imported deer from Canada were also infected with CWD. Since it was thought that this might cause horizontal transmission, 93 deer imported from Canada in 1997 and 130 cohabitating Korean deer were slaughtered and examined. There were no infected Korean deer, but CWD re-occurred on Nov. 20, 2004 and is still under investigation. KEY WORDS: Chronic Wasting Disease (CWD), horizontal transmission. J. Vet. Med. Sci. 67(8): 753–759, 2005
Strain Characterization of the Korean CWD Cases in 2001 and 2004
Yoon-Hee LEE1), Hyun-Joo SOHN1)*, Min-Jeong KIM1), Hyo-Jin KIM1), Won-Yong LEE1), Eun-Im YUN1), Dong-Seob TARK1), In-Soo CHO1) and Aru BALACHANDRAN2) 1)Animal, Plant and Fisheries Quarantine and Inspection Agency, Ministry for Food, Agriculture, Forestry and Fisheries, Anyang 430–757, Republic of Korea 2)National and OIE Reference Laboratory for Scrapie and CWD, Ottawa Laboratory Fallowfield, Ottawa, Canadian Food Inspection Agency, Ottawa, Ontario K2H 8P9, Canada (Received 22 February 2012/Accepted 14 August 2012/Published online in J-STAGE 28 August 2012)
ABSTRACT.
Chronic wasting disease (CWD) has been recognized as a naturally occurring prion disease in North American deer (Odocoileus species), Rocky Mountain elk (Cervus elaphus nelsoni) and moose (Alces alces). The disease was confirmed only in elk in the Republic of Korea in 2001, 2004 and 2005. Epidemiological investigations showed that CWD was introduced via importation of infected elk from Canada between 1994 and 1997. In spite of the increasing geographic distribution and host range of CWD, little is known about the prion strain (s) responsible for distinct outbreaks of the disease. We carried out strain characterization, using transgenic mice overexpressing elk prion protein, including clinical assessment, pathological examination and biochemical analyses, in brain tissues derived following primary through tertiary transmissions. The final incubation period was shortened to approximately 130 dpi due to adaptation. Biochemical profiles remained identical between passages. Lesion profiling in recipient mice brains showed similar patterns of vacuolation scores and intensity. It is clear that there were no biochemical or histopathological differences in Korean CWD cases in 2001 and 2004, suggesting a single strain was responsible for the outbreaks.
KEY WORDS: CWD, Republic of Korea, strain characterization. doi: 10.1292/jvms.12-0077; J. Vet. Med. Sci. 75(1): 95–98, 2013
A Case of Chronic Wasting Disease in an Elk Imported to Korea from Canada
Hyun-Joo SOHN1), Jae-Hoon KIM1)*, Kang-Seuk CHOI1), Jin-Ju NAH1), Yi-Seok JOO1), Young-Hwa JEAN1), Soo-Whan AHN1), Ok-Kyung KIM1), Dae-Yong KIM2) and Aru BALACHANDRAN3) 1)National Veterinary Research and Quarantine Service, Anyang 430–824, 2)Department of Pathology, College of Veterinary Medicine, Seoul National University, Suwon 441–744, Korea and 3)Animal Disease Research Institute, Canadian Food Inspection Agency, Nepean, Ontario, Canada (Received 13 March 2002/Accepted 8 May 2002)
ABSTRACT.
A seven-year-old male elk (Cervus elaphus nelsoni) was euthanized and necropsied after having a 3-week history of body weight loss, emaciation, excessive salivation, teeth grinding, fever, anorexia, and respiratory distress. The elk was imported into Korea from Canada on March 9, 1997. Gross pathologic findings were restricted to a diffuse fibrinous pneumonia. Microscopic lesions included mild neuronal vacuolation and spongiform change in the neuropil of selected brain stem nuclei and generalized astrocytosis. Immunohistochemistry for protease-resistant prion protein (PrPres) was positive in all brain sections but more pronounced in the section of the obex of the medulla. And the PrP res was also detected by western immunoblotting in the brain and spinal cord. All the remaining elk and deer that had been in contact with this elk were destroyed and negative for chronic wasting disease (CWD). To our knowl edge, this is the first case of CWD occurring outside of the U.S.A. and Canada.
KEY WORDS: chronic wasting disease, elk, immunohistochemistry. J. Vet. Med. Sci. 64(9): 855–858, 2002
KOREA CWD TSE Prion
CWD outbreaks in farmed animals were reported in 2001, 2004, 2005, 2010, and *2016 in the Republic of Korea.
Korean CWD was introduced by elk imported from Canada in 1997.
CWD outbreaks in farmed animals were reported in 2001, 2004, 2005, 2010, and ***2016 in the Republic of Korea.
The Korean water deer is the dominant species of wild deer in Korea, with approximately 620 thousand heads (8.0 heads/100 ha) [9].
*2016 in the Republic of Korea.
I LACK A REPORT ON THAT~!???
i have asked about it to Korea officials and scientist, with no reply to date...so, total count on Chronic Wasting Disease CWD TSE Prion in Korea, your guess is good as mine, especially through 2019, ...terry
Between 1996 and 2002, chronic wasting disease was diagnosed in 39 herds of farmed elk in Saskatchewan in a single epidemic. All of these herds were depopulated as part of the Canadian Food Inspection Agency's (CFIA) disease eradication program. Animals, primarily over 12 mo of age, were tested for the presence CWD prions following euthanasia. Twenty-one of the herds were linked through movements of live animals with latent CWD from a single infected source herd in Saskatchewan, 17 through movements of animals from 7 of the secondarily infected herds.
***The source herd is believed to have become infected via importation of animals from a game farm in South Dakota where CWD was subsequently diagnosed (7,4). A wide range in herd prevalence of CWD at the time of herd depopulation of these herds was observed. Within-herd transmission was observed on some farms, while the disease remained confined to the introduced animals on other farms.
KOREA CWD TSE PRION
Chronic Wasting Disease (CWD) outbreaks and surveillance program in the Republic of Korea Chronic Wasting Disease (CWD) outbreaks and surveillance program in the Republic of Korea
Hyun-Joo Sohn, Yoon-Hee Lee, Min-jeong Kim, Eun-Im Yun, Hyo-Jin Kim, Won-Yong Lee, Dong-Seob Tark, In- Soo Cho, Foreign Animal Disease Research Division, National Veterinary Research and Quarantine Service, Republic of Korea
Chronic wasting disease (CWD) has been recognized as an important prion disease in native North America deer and Rocky mountain elks. The disease is a unique member of the transmissible spongiform encephalopathies (TSEs), which naturally affects only a few species. CWD had been limited to USA and Canada until 2000.
On 28 December 2000, information from the Canadian government showed that a total of 95 elk had been exported from farms with CWD to Korea.
These consisted of 23 elk in 1994 originating from the so-called "source farm" in Canada, and 72 elk in 1997, which had been held in pre export quarantine at the "source farm".
Based on export information of CWD suspected elk from Canada to Korea, CWD surveillance program was initiated by the Ministry of Agriculture and Forestry (MAF) in 2001.
All elks imported in 1997 were traced back, however elks imported in 1994 were impossible to identify.
CWD control measures included stamping out of all animals in the affected farm, and thorough cleaning and disinfection of the premises.
In addition, nationwide clinical surveillance of Korean native cervids, and improved measures to ensure reporting of CWD suspect cases were implemented.
*Total of 9 elks were found to be affected. CWD was designated as a notifiable disease under the Act for Prevention of Livestock Epidemics in 2002.
*Additional CWD cases - 12 elks and 2 elks - were diagnosed in 2004 and 2005.
*Since February of 2005, when slaughtered elks were found to be positive, all slaughtered cervid for human consumption at abattoirs were designated as target of the CWD surveillance program.
Currently, CWD laboratory testing is only conducted by National Reference Laboratory on CWD, which is the Foreign Animal Disease Division (FADD) of National Veterinary Research and Quarantine Service (NVRQS).
*In July 2010, one out of 3 elks from Farm 1 which were slaughtered for the human consumption was confirmed as positive.
*Consequently, all cervid - 54 elks, 41 Sika deer and 5 Albino deer - were culled and one elk was found to be positive.
Epidemiological investigations were conducted by Veterinary Epidemiology Division (VED) of NVRQS in collaboration with provincial veterinary services.
*Epidemiologically related farms were found as 3 farms and all cervid at these farms were culled and subjected to CWD diagnosis.
*Three elks and 5 crossbreeds (Red deer and Sika deer) were confirmed as positive at farm 2.
All cervids at Farm 3 and Farm 4 - 15 elks and 47 elks - were culled and confirmed as negative.
Further epidemiological investigations showed that these CWD outbreaks were linked to the importation of elks from Canada in 1994 based on circumstantial evidences.
*In December 2010, one elk was confirmed as positive at Farm 5.
*Consequently, all cervid - 3 elks, 11 Manchurian Sika deer and 20 Sika deer - were culled and one Manchurian Sika deer and seven Sika deer were found to be positive.
This is the first report of CWD in these sub-species of deer.
*Epidemiological investigations found that the owner of the Farm 2 in CWD outbreaks in July 2010 had co-owned the Farm 5.
*In addition, it was newly revealed that one positive elk was introduced from Farm 6 of Jinju-si Gyeongsang Namdo.
All cervid - 19 elks, 15 crossbreed (species unknown) and 64 Sika deer - of Farm 6 were culled, but all confirmed as negative.
: Corresponding author: Dr. Hyun-Joo Sohn (+82-31-467-1867, E-mail: shonhj@korea.kr) 2011 Pre-congress Workshop: TSEs in animals and their environment 5
FULL PAPER
Additional Cases of Chronic Wasting Disease in Imported Deer in Korea
Tae-Yung KIM, Hyun-Joo SHON, Yi-Seok JOO, Un-Kyong MUN, Kyung-Sun KANG, Yong-Soon LEE Author information Keywords: Chronic Wasting Disease (CWD), horizontal transmission JOURNALS FREE ACCESS 2005 Volume 67 Issue 8 Pages 753-759
Abstract
Chronic Wasting Disease (CWD), which had previously occurred only in the U.S.A. and Canada, broke out in a farm at Chungbuk, Korea from imported Canadian deer (Aug. 8, 2001). CWD distribution, through surveillance and epidemiologic investigations, was reported for 93 deer (43 from the CWD originating farm and 50 imported with the CWD originating farm's deer) out of 144 deer (72 from the CWD originating farm and 72 imported with the CWD originating farm's deer) that were breeding at 30 different farms. On Oct. 4 and Oct. 8, 2001, additional cases of CWD were investigated. As a result of slaughtering cohabitating deer, it was verified that other imported deer from Canada were also infected with CWD. Since it was thought that this might cause horizontal transmission, 93 deer imported from Canada in 1997 and 130 cohabitating Korean deer were slaughtered and examined. There were no infected Korean deer, but CWD re-occurred on Nov. 20, 2004 and is still under investigation.
snip...
DISCUSSION
Fig. 3. Present status of farms that sold or resold imported Canadian elk in 1997.
A total of 129 deer (deer/year: 27/1994, 30/1995, and 72/ 1997) were imported from the CWD originating farm in Canada, None ofthe 57 deer imported in 1994 and 1995 fell dead during the advanced surmise period, 60 months, and were confirmed to have no clinical disorders by Canadian authorities and no clinical matters examined. Korean deer were raised for 3.5 years with 144 deer imported in 1997, during which time only 9 of the imported deer became infected, Five of them were imported from the CWD affected farm in Canada and the other 4 were gathered at the CWD affected farm (SK 3 farm) for quarantine and shipped to Korea on the same boat.
It can be considered that horizontal CWD transmission took place, but it is still unclear whether only 4 of the cohabitating Canadian deer became infected. Therefore, Korean authorities should exchange further information on the number of quarantine certificates and coupons with the Canadian Communicable Disease Control Department in order to re— investigate whether only 5 deer were raised at the CWD affected farm, with the other 4 deer being raised at a CWD free farm, or whether the disease was transmitted during shipping. Furthermore, why cohabitating Korean deer were not infected by CWD is considered to be a subject for further research.
The Korean Communicable Disease Control Department did its best to prevent the spread of CWD, but failed to trace back 43 out of 144 deer imported from Canada in 1997,
CHRONIC WASTING DISEASE CASES IN KOREA 759
Among these, 25 deer were from the CWD affected farm and 18 deer were imported with the deer from the CWD affected farm (Table 5). The department is currently investigating a new case of CWD found on Nov, 20, 2004 to determine whether it is a deer that was missing in 2001, or a vertically or horizontally transmitted deer.
ACKNOWLEDGMENTS, This work was supported by the National Veterinary Research & Quarantine Service, Anyang 430-016, Korea.
REFERENCES
Strain Characterization of the Korean CWD Cases in 2001 and 2004
Yoon-Hee LEE1), Hyun-Joo SOHN1)*, Min-Jeong KIM1), Hyo-Jin KIM1), Won-Yong LEE1), Eun-Im YUN1), Dong-Seob TARK1), In-Soo CHO1) and Aru BALACHANDRAN2)
1)Animal, Plant and Fisheries Quarantine and Inspection Agency, Ministry for Food, Agriculture, Forestry and Fisheries, Anyang 430–757, Republic of Korea
2)National and OIE Reference Laboratory for Scrapie and CWD, Ottawa Laboratory Fallowfield, Ottawa, Canadian Food Inspection Agency, Ottawa, Ontario K2H 8P9, Canada
(Received 22 February 2012/Accepted 14 August 2012/Published online in J-STAGE 28 August 2012)
ABSTRACT. Chronic wasting disease (CWD) has been recognized as a naturally occurring prion disease in North American deer (Odocoileus species), Rocky Mountain elk (Cervus elaphus nelsoni) and moose (Alces alces). The disease was confirmed only in elk in the Republic of Korea in 2001, 2004 and 2005. Epidemiological investigations showed that CWD was introduced via importation of infected elk from Canada between 1994 and 1997. In spite of the increasing geographic distribution and host range of CWD, little is known about the prion strain (s) responsible for distinct outbreaks of the disease. We carried out strain characterization, using transgenic mice overexpressing elk prion protein, including clinical assessment, pathological examination and biochemical analyses, in brain tissues derived following primary through tertiary transmissions. The final incubation period was shortened to approximately 130 dpi due to adaptation. Biochemical profiles remained identical between passages. Lesion profiling in recipient mice brains showed similar patterns of vacuolation scores and intensity. It is clear that there were no biochemical or histopathological differences in Korean CWD cases in 2001 and 2004, suggesting a single strain was responsible for the outbreaks.
Chronic wasting disease (CWD) has been recognized as an important prion disease in North American deer and Rocky mountain elk [13]. This disease was confirmed only in elk in the Republic of Korea in 2001, 2004 and 2005 [7, 10]. Additional CWD cases were observed in red deer, sika deer, and crossbred sika and red deer in 2010 (unpublished data). However, these cases were not included in the present study, which focuses only on elk CWD. Recently, using a model of transgenic mice overexpressing mule deer prion, the possibility of at least two CWD strains existing in North American cervids was raised [1]. More evidence on the two distinct CWD strains that originated from the mule deer was suggested using the ferret model [9] and from Syrian hamster model studies, and the emergence of a new “wasting strain” (WST) would appear to have occurred in white-tailed deer [2]. Epidemiological investigations showed that CWD was introduced to the Korean peninsula via importation of infected elk from Canada in 1994, 1995 and 1997 [7]. It is possible that more than one strain might have been introduced from Canada, although a Canadian retrospective study underway shows no emergence of other phenotypes so far (Dr. Gordon Mitchell, personal comm.).
snip...
KEY WORDS: CWD, Republic of Korea, strain characterization.
doi: 10.1292/jvms.12-0077; J. Vet. Med. Sci. 75(1): 95–98, 2013
see full text;
Friday, May 13, 2011
Chronic Wasting Disease (CWD) outbreaks and surveillance program in the Republic of Korea
A Case of Chronic Wasting Disease in an Elk Imported to Korea from Canada
Hyun-Joo SOHN, Jae-Hoon KIM, Kang-Seuk CHOI, Jin-Ju NAH, Yi-Seok JOO, Young-Hwa JEAN, Soo-Whan AHN, Ok-Kyung KIM, Dae-Yong KIM, Aru BALACHANDRAN Author information Keywords: chronic wasting disease, elk, immunohistochemistry JOURNALS FREE ACCESS 2002 Volume 64 Issue 9 Pages 855-858
Abstract A seven-year-old male elk (Cervus elaphus nelsoni) was euthanized and necropsied after having a 3-week history of body weight loss, emaciation, excessive salivation, teeth grinding, fever, anorexia, and respiratory distress. The elk was imported into Korea from Canada on March 9, 1997. Gross pathologic findings were restricted to a diffuse fibrinous pneumonia. Microscopic lesions included mild neuronal vacuolation and spongiform change in the neuropil of selected brain stem nuclei and generalized astrocytosis. Immunohistochemistry for protease-resistant prion protein (PrPres) was positive in all brain sections but more pronounced in the section of the obex of the medulla. And the PrPres was also detected by western immunoblotting in the brain and spinal cord. All the remaining elk and deer that had been in contact with this elk were destroyed and negative for chronic wasting disease (CWD). To our knowledge, this is the first case of CWD occurring outside of the U.S.A. and Canada.
References (11)
see full text
P-147 Infection and detection of PrPCWD in soil from CWD infected farm in Korea
Hyun Joo Sohn, Kyung Je Park, In Soon Roh, Hyo Jin Kim, Hoo Chang Park, Byounghan Kim
Animal and Plant Quarantine Agency (QIA), Korea
Transmissible spongiform encephalopathy (TSE) is a fatal neurodegenerative disorder, which is so-called as prion diseases due to the causative agents (PrPSc). TSEs are believed to be due to the template-directed accumulation of disease-associated prion protein, generally designated PrPSc. Chronic wasting disease (CWD) is the prion disease that is known spread horizontally. CWD has confirmed last in Republic of Korea in 2010 since first outbreak of CWD in 2001. The environmental reservoirs mediate the transmission of this disease. The significant levels of infectivity have been detected in the saliva, urine, and feces of TSE-infected animals. Using serial protein misfolding cyclic amplification (sPMCA), we developed a detection method for CWD PrPSc in soil from CWD affected farm in 2010. We found to detect PrPSc in soil from CWD infected farm, but not detect PrPSc in soil of wild cervid habitats and normal cervid farm in Korea. We also tried the bioassay on transgenic mice overexpressing elk prion protein (TgElk mice) to confirm infectivity of CWD-infected farm soil and washing solution of it. As the results, there was the presence of infectious prions in them. The attack rates were each 12.5% (1/8, soil) and 100% (6/6, soil washing solution). Our method appears to be a very useful technique for monitoring PrPSc levels in environmental conditions.
P-153
Experimental oral transmission of chronic wasting disease to sika deer (Cervus nippon)
Gordon Mitchell1, Hyun-Joo Sohn2, Yoon-Hee Lee2, Antanas Staskevicius1, Nishandan Yogasingam1, Ines Walther1, In-Soo Cho2, Aru Balachandran1
1National & OIE Reference Laboratory for Scrapie and CWD, Canadian Food Inspection Agency, Ottawa, Ontario, Canada; 2Animal, Plant and Fisheries Quarantine and Inspection Agency, Ministry for Food, Agriculture, Forestry and Fisheries, Anyang, Republic of Korea
Chronic wasting disease (CWD) persists in North American cervids, and epidemiological evidence indicates CWD was introduced into the Republic of Korea approximately twenty years ago through the importation of an infected elk (Cervus elaphus) from Canada. Additional cases of CWD have since been detected in Korean elk, and recently for the first time in their farmed sika deer (Cervus nippon). Sika deer are also found in regions of North America and Europe, although natural transmission to these populations has not been detected. Understanding the pathogenesis of CWD in this species is therefore essential to developing diagnostic and disease control strategies.
Six sika deer were orally inoculated with a brain homogenate prepared from a farmed Canadian elk with clinical CWD. Four deer developed clinical signs consistent with CWD and were euthanized between 21 and 24 months post-inoculation (mpi). Two deer were removed from the study due to intercurrent disease, at 4 and 11 mpi. At necropsy, an array of tissues and bodily fluids were sampled and preliminary testing of brainstem and lymphoid tissue by ELISA, immunohistochemistry and western blot confirmed CWD transmission. Aggregates of pathological prion protein (PrPCWD) were detected in the retropharyngeal lymph nodes, but not brainstem of the deer sampled at 4 mpi. All other deer, including the deer tested at 11 mpi, displayed marked PrPCWD accumulation in brainstem and lymphoid tissues. Further immunohistochemical analysis of tissues from sika deer with clinical disease revealed widespread PrPCWD deposition in Iymphoreticular tissues, central and peripheral nervous systems, the gastrointestinal tract and neuroendocrine tissues. Western blot molecular profiles in sika deer brainstem samples were similar to the original elk inoculum. Ante-mortem biopsy of recto-anal mucosal associated lymphoid tissue, tested using immunohistochemistry, detected infected sika deer prior to the onset of clinical disease. These findings corroborate studies in other cervids, identifying early and widespread PrPCWD accumulation in tissues following oral inoculation. Efficient transmission of CWD to sika deer dictates a precautionary approach when exposing this species to environments or other cervids potentially infected with CWD.
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Prion 2016 Conference Poster Abstracts
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SUNDAY, JULY 14, 2019
Korea Chronic Wasting Disease CWD TSE Prion additional cases were observed in red deer, sika deer, and their crossbred deer in 2010 and 2016, beyond that, anyone's guess
6 Conclusion
The department considers that animal biosecurity risks associated with bulk wheat sourced from the Canadian Prairies for processing can be effectively managed in accordance with the risk management measures outlined in this document. The department considers that the application of those measures will achieve Australia’s ALOP in a least trade-restrictive manner.
THURSDAY, OCTOBER 25, 2018
Norway New additional requirements for imports of hay and straw for animal feed from countries outside the EEA due to CWD TSE Prion
Norway New additional requirements for imports of hay and straw for animal feed from countries outside the EEA due to CWD TSE Prion
$$$$$
***> NORWAY CWD UPDATE December 2018
Report from the Norwegian Scientific Committee for Food and Environment (VKM) 2018: 16
Factors that can contribute to spread of CWD – an update on the situation in Nordfjella, Norway
Opinion of Panel on biological hazards of the Norwegian Scientific Committee for Food and Environment
13.12.2018
ISBN: 978-82-8259-316-8
ISSN: 2535-4019
Norwegian Scientific Committee for Food and Environment (VKM)
Po 222 Skøyen
0213 Oslo
Norway
FRIDAY, DECEMBER 14, 2018
Norway, Nordfjella VKM 2018 16 Factors that can contribute to spread of CWD TSE Prion UPDATE December 14, 2018
THURSDAY, OCTOBER 25, 2018
***> Norway New additional requirements for imports of hay and straw for animal feed from countries outside the EEA due to CWD TSE Prion
new link;
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?
FRIDAY, SEPTEMBER 05, 2014
CFIA CWD and Grain Screenings due to potential risk factor of spreading via contamination of grain, oil seeds, etc.
FRIDAY, SEPTEMBER 27, 2013
Uptake of Prions into Plants
WEDNESDAY, OCTOBER 16, 2019
Australia Assessment of bulk wheat from Canada Part B: Animal biosecurity risk advice, CWD TSE Prion concerns are mounting
THURSDAY, SEPTEMBER 26, 2019
Sweden The third case of CWD in moose in Arjeplog is now established
SATURDAY, JUNE 01, 2019
Sweden Documents Another Case of Chronic Wasting Disease CWD TSE Prion Norrbotten
FRIDAY, APRIL 12, 2019
Sweden Wasting Disease (CWD) discovered on moose in Norrbotten County
FRIDAY, MARCH 29, 2019
First Detection of Chronic Wasting Disease in a Wild Red Deer (Cervus elaphus) in Europe
FINLAND MOOSE FOUND DEAD IN FOREST WITH CHRONIC WASTING DISEASE 8.3.2018 12:56
The chronic wasting disease (CWD) has been found in a moose or European elk (Alces alces) for the first time ever in Finland. The disease was diagnosed in Kuhmo in a 15-year old moose that had died naturally. The results of the analyses carried out by Finnish Food Safety Authority Evira have been verified by a EU reference laboratory. Species of the deer family, known as “cervids”, can suffer from the chronic wasting disease, and it is always fatal. The disease is not known to have been contracted by people.
Norway was before this case the only European country where CWD has been diagnosed. The monitoring of the occurrence of the disease was intensified from the beginning of 2018 in Finland and five other EU Member States.
In Finland, the occurrence of the disease has been studied already since 2003. None of the ca. 2 500 samples analysed so far had tested positive for the disease. The monitoring of the disease will now be further intensified in the Kuhmo and Kainuu region. Hunters are going to be provided with more instructions before the start of the next hunting season, if appropriate.
The chronic wasting disease is not known to have been contracted by people. Moose meat is safe to eat and no restrictions are imposed on the sales and exportation of meat of animals of the deer family. As a precautionary measure the export of live animals of the deer family to other countries will be discontinued for now.
CWD is a slowly progressing disease of deer, elk, reindeer, and moose which always leads to death. The chronic wasting disease is a prion disease and related to the BSE (bovine spongiform encephalopathy) and other TSE diseases (transmissible spongiform encephalopathy). The disease is common in North America. The moose found in Kuhmo did not suffer from the North American, highly contagious form of the chronic wasting disease. The disease seems to resemble most the form of cervid TSE diagnosed in Norway, which appears to be found incidentally in individual animals of the deer family.
For more information, please contact:
Leena Räsänen, Director, tel. +358 50 388 6518 (Food Safety)
Terhi Laaksonen, Head of Unit, tel. +358 40 159 5812 (Control of Animal Diseases)
Sirkka-Liisa Korpenfelt, Senior Resarcher, tel. + 358 50 351 0308 (Laboratory Analyses)
Antti Oksanen, Research Professor, tel. +358 44 561 6491 (Wild Animal Diseases)
Kajsa Hakulin, Ministerial Advisor, Ministry of Agriculture and Forestry, tel. +358 295 162361 (National and EU Legislation)
https://www.evira.fi/en/animals/current_issues/2018/moose-found-dead-in-forest-with-chronic-wasting-disease/
SATURDAY, MARCH 10, 2018
FINLAND REPORTS FIRST CASE OF CHRONIC WASTING DISEASE CWD TSE PRION IN A moose or European elk (Alces alces)
WEDNESDAY, MARCH 06, 2019
Norway The Madness Continues in Nordfjella Chronic Wasting Disease CWD TSE Prion
FRIDAY, OCTOBER 25, 2019
27th ANNUAL REPORT 2018 CREUTZFELDT-JAKOB DISEASE SURVEILLANCE IN THE UK
Diagnosis and Reporting of Creutzfeldt-Jakob Disease
Singeltary, Sr et al. JAMA.2001; 285: 733-734. Vol. 285 No. 6, February 14, 2001 JAMA Diagnosis and Reporting of Creutzfeldt-Jakob Disease
To the Editor:
In their Research Letter, Dr Gibbons and colleagues1 reported that the annual US death rate due to Creutzfeldt-Jakob disease (CJD) has been stable since 1985. These estimates, however, are based only on reported cases, and do not include misdiagnosed or preclinical cases. It seems to me that misdiagnosis alone would drastically change these figures. An unknown number of persons with a diagnosis of Alzheimer disease in fact may have CJD, although only a small number of these patients receive the postmortem examination necessary to make this diagnosis. Furthermore, only a few states have made CJD reportable. Human and animal transmissible spongiform encephalopathies should be reportable nationwide and internationally..
Terry S. Singeltary, Sr Bacliff, Tex
1. Gibbons RV, Holman RC, Belay ED, Schonberger LB. Creutzfeldt-Jakob disease in the United States: 1979-1998. JAMA. 2000;284:2322-2323.
doi:10.1016/S1473-3099(03)00715-1 Copyright © 2003 Published by Elsevier Ltd. Newsdesk
Tracking spongiform encephalopathies in North America
Xavier Bosch
Available online 29 July 2003.
Volume 3, Issue 8, August 2003, Page 463
“My name is Terry S Singeltary Sr, and I live in Bacliff, Texas. I lost my mom to hvCJD (Heidenhain variant CJD) and have been searching for answers ever since. What I have found is that we have not been told the truth. CWD in deer and elk is a small portion of a much bigger problem..” ...
January 28, 2003; 60 (2) VIEWS & REVIEWS
Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob disease in the United States
Ermias D. Belay, Ryan A. Maddox, Pierluigi Gambetti, Lawrence B. Schonberger
First published January 28, 2003, DOI: https://doi.org/10.1212/01.WNL.0000036913.87823.D6
Abstract
Transmissible spongiform encephalopathies (TSEs) attracted increased attention in the mid-1980s because of the emergence among UK cattle of bovine spongiform encephalopathy (BSE), which has been shown to be transmitted to humans, causing a variant form of Creutzfeldt-Jakob disease (vCJD). The BSE outbreak has been reported in 19 European countries, Israel, and Japan, and human cases have so far been identified in four European countries, and more recently in a Canadian resident and a US resident who each lived in Britain during the BSE outbreak. To monitor the occurrence of emerging forms of CJD, such as vCJD, in the United States, the Centers for Disease Control and Prevention has been conducting surveillance for human TSEs through several mechanisms, including the establishment of the National Prion Disease Pathology Surveillance Center. Physicians are encouraged to maintain a high index of suspicion for vCJD and use the free services of the pathology center to assess the neuropathology of clinically diagnosed and suspected cases of CJD or other TSEs.
Received May 7, 2002. Accepted August 28, 2002.
RE-Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob disease in the United States
Terry S. Singeltary, retired (medically)
Published March 26, 2003
26 March 2003
Terry S. Singeltary, retired (medically) CJD WATCH
I lost my mother to hvCJD (Heidenhain Variant CJD). I would like to comment on the CDC's attempts to monitor the occurrence of emerging forms of CJD. Asante, Collinge et al [1] have reported that BSE transmission to the 129-methionine genotype can lead to an alternate phenotype that is indistinguishable from type 2 PrPSc, the commonest sporadic CJD. However, CJD and all human TSEs are not reportable nationally. CJD and all human TSEs must be made reportable in every state and internationally. I hope that the CDC does not continue to expect us to still believe that the 85%+ of all CJD cases which are sporadic are all spontaneous, without route/source. We have many TSEs in the USA in both animal and man. CWD in deer/elk is spreading rapidly and CWD does transmit to mink, ferret, cattle, and squirrel monkey by intracerebral inoculation. With the known incubation periods in other TSEs, oral transmission studies of CWD may take much longer. Every victim/family of CJD/TSEs should be asked about route and source of this agent. To prolong this will only spread the agent and needlessly expose others. In light of the findings of Asante and Collinge et al, there should be drastic measures to safeguard the medical and surgical arena from sporadic CJDs and all human TSEs. I only ponder how many sporadic CJDs in the USA are type 2 PrPSc?
Reply to Singletary Ryan A. Maddox, MPH Other Contributors: Published March 26, 2003
Mr. Singletary raises several issues related to current Creutzfeldt- Jakob disease (CJD) surveillance activities. Although CJD is not a notifiable disease in most states, its unique characteristics, particularly its invariably fatal outcome within usually a year of onset, make routine mortality surveillance a useful surrogate for ongoing CJD surveillance.[1] In addition, because CJD is least accurately diagnosed early in the course of illness, notifiable-disease surveillance could be less accurate than, if not duplicative of, current mortality surveillance.[1] However, in states where making CJD officially notifiable would meaningfully facilitate the collection of data to monitor for variant CJD (vCJD) or other emerging prion diseases, CDC encourages the designation of CJD as a notifiable disease.[1] Moreover, CDC encourages physicians to report any diagnosed or suspected CJD cases that may be of special public health importance (e.g...., vCJD, iatrogenic CJD, unusual CJD clusters).
As noted in our article, strong evidence is lacking for a causal link between chronic wasting disease (CWD) of deer and elk and human disease,[2] but only limited data seeking such evidence exist. Overall, the previously published case-control studies that have evaluated environmental sources of infection for sporadic CJD have not consistently identified strong evidence for a common risk factor.[3] However, the power of a case-control study to detect a rare cause of CJD is limited, particularly given the relatively small number of subjects generally involved and its long incubation period, which may last for decades. Because only a very small proportion of the US population has been exposed to CWD, a targeted surveillance and investigation of unusual cases or case clusters of prion diseases among persons at increased risk of exposure to CWD is a more efficient approach to detecting the possible transmission of CWD to humans. In collaboration with appropriate local and state health departments and the National Prion Disease Pathology Surveillance Center, CDC is facilitating or conducting such surveillance and case- investigations, including related laboratory studies to characterize CJD and CWD prions.
Mr. Singletary also expresses concern over a recent publication by Asante and colleagues indicating the possibility that some sporadic CJD cases may be attributable to bovine spongiform encephalopathy (BSE).[4] The authors reported that transgenic mice expressing human prion protein homozygous for methionine at codon 129, when inoculated with BSE prions, developed a molecular phenotype consistent with a subtype of sporadic CJD. Although the authors implied that BSE might cause a sporadic CJD-like illness among persons homozygous for methionine, the results of their research with mice do not necessarily directly apply to the transmission of BSE to humans. If BSE causes a sporadic CJD-like illness in humans, an increase in sporadic CJD cases would be expected to first occur in the United Kingdom, where the vast majority of vCJD cases have been reported. In the United Kingdom during 1997 through 2002, however, the overall average annual mortality rate for sporadic CJD was not elevated; it was about 1 case per million population per year. In addition, during this most recent 6-year period following the first published description of vCJD in 1996, there was no increasing trend in the reported annual number of UK sporadic CJD deaths.[3, 5] Furthermore, surveillance in the UK has shown no increase in the proportion of sporadic CJD cases that are homozygous for methionine (Will RG, National CJD Surveillance Unit, United Kingdom, 2003; personal communication)..
References
1. Gibbons RV, Holman RC, Belay ED, Schonberger LB. Diagnosis and reporting of Creutzfeldt-Jakob disease. JAMA 2001;285:733-734.
2. Belay ED, Maddox RA, Gambetti P, Schonberger LB. Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob disease in the United States.. Neurology 2003;60:176-181.
3. Belay ED. Transmissible spongiform encephalopathies in humans. Annu Rev Microbiol 1999;53:283-314.
4. Asante EA, Linehan JM, Desbruslais M, et al. BSE prions propagate as either variant CJD-like or sporadic CJD-like prion strains in transgenic mice expressing human prion protein. EMBO J 2002;21:6358-6366.
5. The UK Creutzfeldt-Jakob Disease Surveillance Unit. CJD statistics. Available at: http://www.cjd.ed.ac.uk/figures.htm. Accessed February 18, 2003.
Competing Interests: None declared.
Volume 2: Science
4. The link between BSE and vCJD
Summary 4.29 The evidence discussed above that vCJD is caused by BSE seems overwhelming. Uncertainties exist about the cause of CJD in farmers, their wives and in several abattoir workers. It seems that farmers at least might be at higher risk than others in the general population. 1 Increased ascertainment (ie, increased identification of cases as a result of greater awareness of the condition) seems unlikely, as other groups exposed to risk, such as butchers and veterinarians, do not appear to have been affected. The CJD in farmers seems to be similar to other sporadic CJD in age of onset, in respect to glycosylation patterns, and in strain-typing in experimental mice. Some farmers are heterozygous for the methionine/valine variant at codon 129, and their lymphoreticular system (LRS) does not contain the high levels of PrPSc found in vCJD.
***>It remains a remote possibility that when older people contract CJD from BSE the resulting phenotype is like sporadic CJD and is distinct from the vCJD phenotype in younger people...end
BSE INQUIRY
SATURDAY, JUNE 23, 2018
CDC
***> Diagnosis of Methionine/Valine Variant Creutzfeldt-Jakob Disease by Protein Misfolding Cyclic Amplification
Volume 24, Number 7—July 2018 Dispatch
Diagnosis and Reporting of Creutzfeldt-Jakob Disease
2 January 2000 British Medical Journal U.S.
Scientist should be concerned with a CJD epidemic in the U.S., as well
15 November 1999 British Medical Journal hvCJD in the USA * BSE in U.S..
FRIDAY, NOVEMBER 08, 2019
EFSA Panel on Biological Hazards (BIOHAZ) Update on chronic wasting disease (CWD) III
Terry S. Singeltary Sr.
posted by Terry S. Singeltary Sr. at
10:54 AM
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