Alberta Canada Scrapie, a disease related to mad cow, found in two flocks
Flocks infected with Scrapie in Canada – 2019
The CFIA, in co-operation with provincial governments and industry, launched a national scrapie surveillance program in 2005. Under the program, producers are encouraged to report animals that die on the farm or exhibit symptoms of the disease.
In addition, scrapie is a reportable disease under the Health of Animals Regulations. This means that all suspected cases must be reported to the CFIA.
Current as of: 2019-06-30
Sheep flocks and/or goat herds confirmed to be infected with classical scrapie in Canada in 2019
Date confirmed Location Animal type infected
June 21, 2019 Alberta Sheep
June 21, 2019 Alberta Sheep
Scrapie, a disease related to mad cow, found in two flocks of sheep in Alberta
BY THE CANADIAN PRESS
Posted Jul 19, 2019 6:31 am MDT Last Updated Jul 19, 2019 at 6:31 am MDT (Pixabay) OTTAWA – The Canadian Food Inspection Agency says some sheep in Alberta have been infected with scrapie, a fatal disease that affects the animals’ nervous system.
The federal agency’s website says classic scrapie, which can be transmitted to other sheep and goats, was confirmed last month in two flocks in Central Alberta.
As a result, the agency said in an email that the two herds are under quarantine.
FULL DETAILS
The movements of the diseased animals are also being traced and epidemiological data is being gathered. No sheep have been killed.
Scrapie belongs to the family of diseases that includes mad cow disease in cattle, chronic wasting disease in deer and elk, and Creutzfeldt-Jakob disease in humans.
Health Canada says there is no known link between scrapie and human health.
The CFIA says scrapie can only be seen in adult sheep between two and five years of age and can take years to develop.
Once an animal appears ill it typically dies within a few months.
> Health Canada says there is no known link between scrapie and human health.
factually, and scientifically, this statement is incorrect.
sheep scrapie has been linked to human tse prion, as in sporadic cjd. see;
ZOONOSIS OF SCRAPIE TSE PRION
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***
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***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.
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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.
1: J Infect Dis 1980 Aug;142(2):205-8
Oral transmission of kuru, Creutzfeldt-Jakob disease, and scrapie to nonhuman primates.
Gibbs CJ Jr, Amyx HL, Bacote A, Masters CL, Gajdusek DC.
Kuru and Creutzfeldt-Jakob disease of humans and scrapie disease of sheep and goats were transmitted to squirrel monkeys (Saimiri sciureus) that were exposed to the infectious agents only by their nonforced consumption of known infectious tissues. The asymptomatic incubation period in the one monkey exposed to the virus of kuru was 36 months; that in the two monkeys exposed to the virus of Creutzfeldt-Jakob disease was 23 and 27 months, respectively; and that in the two monkeys exposed to the virus of scrapie was 25 and 32 months, respectively. Careful physical examination of the buccal cavities of all of the monkeys failed to reveal signs or oral lesions. One additional monkey similarly exposed to kuru has remained asymptomatic during the 39 months that it has been under observation.
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The successful transmission of kuru, Creutzfeldt-Jakob disease, and scrapie by natural feeding to squirrel monkeys that we have reported provides further grounds for concern that scrapie-infected meat may occasionally give rise in humans to Creutzfeldt-Jakob disease.
PMID: 6997404
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6997404&dopt=Abstract
Recently the question has again been brought up as to whether scrapie is transmissible to man. This has followed reports that the disease has been transmitted to primates. One particularly lurid speculation (Gajdusek 1977) conjectures that the agents of scrapie, kuru, Creutzfeldt-Jakob disease and transmissible encephalopathy of mink are varieties of a single "virus". The U.S. Department of Agriculture concluded that it could "no longer justify or permit scrapie-blood line and scrapie-exposed sheep and goats to be processed for human or animal food at slaughter or rendering plants" (ARC 84/77)" The problem is emphasised by the finding that some strains of scrapie produce lesions identical to the once which characterise the human dementias"
Whether true or not. the hypothesis that these agents might be transmissible to man raises two considerations. First, the safety of laboratory personnel requires prompt attention. Second, action such as the "scorched meat" policy of USDA makes the solution of the acrapie problem urgent if the sheep industry is not to suffer grievously.
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76/10.12/4.6
Nature. 1972 Mar 10;236(5341):73-4.
Transmission of scrapie to the cynomolgus monkey (Macaca fascicularis).
Gibbs CJ Jr, Gajdusek DC.
Nature 236, 73 - 74 (10 March 1972); doi:10.1038/236073a0
Transmission of Scrapie to the Cynomolgus Monkey (Macaca fascicularis)
C. J. GIBBS jun. & D. C. GAJDUSEK
National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, Maryland
SCRAPIE has been transmitted to the cynomolgus, or crab-eating, monkey (Macaca fascicularis) with an incubation period of more than 5 yr from the time of intracerebral inoculation of scrapie-infected mouse brain. The animal developed a chronic central nervous system degeneration, with ataxia, tremor and myoclonus with associated severe scrapie-like pathology of intensive astroglial hypertrophy and proliferation, neuronal vacuolation and status spongiosus of grey matter. The strain of scrapie virus used was the eighth passage in Swiss mice (NIH) of a Compton strain of scrapie obtained as ninth intracerebral passage of the agent in goat brain, from Dr R. L. Chandler (ARC, Compton, Berkshire).
Wednesday, February 16, 2011
IN CONFIDENCE
SCRAPIE TRANSMISSION TO CHIMPANZEES
IN CONFIDENCE
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.
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.
***> 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. <***
Scrapie Transmits To Pigs By Oral Route, what about the terribly flawed USA tse prion feed ban?
Research Project: Pathobiology, Genetics, and Detection of Transmissible Spongiform Encephalopathies Location: Virus and Prion Research
2017 Annual Report
1a. Objectives (from AD-416):
Objective 1: Investigate the mechanisms of protein misfolding in prion disease, including the genetic determinants of misfolding of the prion protein and the environmental influences on protein misfolding as it relates to prion diseases. Subobjective 1.A: Investigate the differences in the unfolded state of wild-type and disease associated prion proteins to better understand the mechanism of misfolding in genetic prion disease. Subobjective 1.B: Investigate the influence of metal ions on the misfolding of the prion protein in vitro to determine if environmental exposure to metal ions may alter disease progression. Objective 2: Investigate the pathobiology of prion strains in natural hosts, including the influence of prion source genotype on interspecies transmission and the pathobiology of atypical transmissible spongiform encephalopathies (TSEs). Subobjective 2.A: Investigate the pathobiology of atypical TSEs. Subobjective 2.B: Investigate the influence of prion source genotype on interspecies transmission. Objective 3: Investigate sampling methodologies for antemortem detection of prion disease, including the utility of blood sampling as a means to assess prion disease status of affected animals and the utility of environmental sampling for monitoring herd prion disease status. Subobjective 3.A: Investigate the utility of blood sampling as a means to assess prion disease status of affected animals. Subobjective 3.B: Investigate the utility of environmental sampling for monitoring herd prion disease status.
1b. Approach (from AD-416):
The studies will focus on three animal transmissible spongiform encephalopathy (TSE) agents found in the United States: bovine spongiform encephalopathy (BSE); scrapie of sheep and goats; and chronic wasting disease (CWD) of deer, elk, and moose. The research will address sites of protein folding and misfolding as it relates to prion disease, accumulation of misfolded protein in the host, routes of infection, and ante mortem diagnostics with an emphasis on controlled conditions and natural routes of infection. Techniques used will include spectroscopic monitoring of protein folding/misfolding, clinical exams, histopathology, immunohistochemistry, and biochemical analysis of proteins. The enhanced knowledge gained from this work will help understand the underlying mechanisms of prion disease and mitigate the potential for unrecognized epidemic expansions of these diseases in populations of animals that could either directly or indirectly affect food animals.
3. Progress Report:
All 8 project plan milestones for FY17 were fully met. Research efforts directed toward meeting objective 1 of our project plan center around the production of recombinant prion protein from either bacteria or mammalian tissue culture systems and collection of thermodynamic data on the folding of the recombinant prion protein produced. Both bacterial and mammalian expression systems have been established. Thermodynamic data addressing the denatured state of wild-type and a disease associated variant of bovine prion protein has been collected and a manuscript is in preparation. In research pertaining to objective 2, all studies have been initiated and animals are under observation for the development of clinical signs. The animal studies for this objective are long term and will continue until onset of clinical signs. In vitro studies planned in parallel to the animals studies have similarly been initiated and are ongoing. Objective 3 of the project plan focuses on the detection of disease associated prion protein in body fluids and feces collected from a time course study of chronic wasting disease inoculated animals. At this time samples are being collected as planned and methods for analysis are under development.
4. Accomplishments
1. Showed that swine are potential hosts for the scrapie agent. A naturally occurring prion disease has not been recognized in swine, but the agent of bovine spongiform encephalopathy does transmit to swine by experimental routes. Swine are thought to have a robust species barrier when exposed to the naturally occurring prion diseases of other species, but the susceptibility of swine to the agent of sheep scrapie has not been thoroughly tested. ARS researchers at Ames, Iowa conducted this experiment to test the susceptibility of swine to U.S. scrapie isolates by intracranial and oral inoculation. Necropsies were done on a subset of animals at approximately 6 months post inoculation (PI): the time the pigs were expected to reach market weight. Remaining pigs were maintained and monitored for clinical signs of transmissible spongiform encephalopathies (TSE) until study termination at 80 months PI or when removed due to intercurrent disease. Brain samples were examined by multiple diagnostic approaches, and for a subset of pigs in each inoculation group, bioassay in mice expressing porcine prion protein. At 6 months PI, no evidence of scrapie infection was noted by any diagnostic method. 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.
2. Determined that pigs naturally exposed to chronic wasting disease (CWD) may act as a reservoir of CWD infectivity. Chronic wasting disease is a naturally occurring, fatal, neurodegenerative disease of cervids. The potential for swine to serve as a host for the agent of CWD disease is unknown. The purpose of this study was to investigate the susceptibility of swine to the CWD agent following experimental oral or intracranial inoculation. Pigs were assigned to 1 of 3 groups: intracranially inoculated; orally inoculated; or non-inoculated. At market weight age, half of the pigs in each group were tested ('market weight' groups). The remaining pigs ('aged' groups) were allowed to incubate for up to 73 months post inoculation (MPI). Tissues collected at necropsy were examined for disease-associated prion protein (PrPSc) by multiple diagnostic methods. Brain samples from selected pigs were bioassayed in mice expressing porcine prion protein. Some pigs from each inoculated group were positive by one or more tests. Bioassay was positive in 4 out of 5 pigs assayed. Although only small amounts of PrPSc were detected using sensitive methods, this study demonstrates that pigs can serve as hosts for CWD. Detection of infectivity in orally inoculated pigs using mouse bioassay raises the possibility that naturally exposed pigs could act as a reservoir of CWD infectivity. Currently, swine rations in the U.S. could contain animal derived components including materials from deer or elk. In addition, feral swine could be exposed to infected carcasses in areas where CWD is present in wildlife populations. The current feed ban in the U.S. is based exclusively on keeping tissues from TSE infected cattle from entering animal feeds. These results indicating the susceptibility of pigs to CWD, 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.
3. Developed a method for amplification and discrimination of the 3 forms of BSE in cattle. The prion protein (PrP) is a protein that is the causative agent of transmissible spongiform encephalopathies (TSEs). The disease process involves conversion of the normal cellular PrP to a pathogenic misfolded conformation. This conversion process can be recreated in the lab using a misfolding amplification process known as real-time quaking induced conversion (RT-QuIC). RT-QuIC allows the detection of minute amounts of the abnormal infectious form of the prion protein by inducing misfolding in a supplied substrate. Although RT-QuIC has been successfully used to detect pathogenic PrP with substrates from a variety of host species, prior to this work bovine prion protein had not been proven for its practical uses for RT-QuIC. We demonstrated that prions from transmissible mink encephalopathy (TME) and BSE-infected cattle can be detected with using bovine prion proteins with RT-QuIC, and developed an RT-QuIC based approach to discriminate different forms of BSE. This rapid and robust method, both to detect and discriminate BSE types, is of importance as the economic implications for different types of BSE vary greatly.
Review Publications
Hwang, S., Greenlee, J.J., Nicholson, E.M. 2017. Use of bovine recombinant prion protein and real-time quaking-induced conversion to detect cattle transmissible mink encephalopathy prions and discriminate classical and atypical L- and H-type bovine spongiform encephalopathy. PLoS One. 12(2):e0172391.
Moore, S., Kunkle, R., Greenlee, M., Nicholson, E., Richt, J., Hamir, A., Waters, W., Greenlee, J. 2016. Horizontal transmission of chronic wasting disease in reindeer. Emerging Infectious Diseases. 22(12):2142-2145. doi:10.3201/eid2212.160635.
Moore, S.J., West Greenlee, M.H., Smith, J.D., Vrentas, C.E., Nicholson, E.M., Greenlee, J.J. 2016. A comparison of classical and H-type bovine spongiform encephalopathy associated with E211K prion protein polymorphism in wild type and EK211 cattle following intracranial inoculation. Frontiers in Veterinary Science. 3:78.
Greenlee, J.J., Kunkle, R.A., Smith, J.D., West Greenlee, M.H. 2016. Scrapie in swine: a diagnostic challenge. Food Safety. 4(4):110-114. Kondru, N., Manne, S., Greenlee, J., West Greenlee, H., Anantharam, V., Halbur, P., Kanthasamy, A., Kanthasamy, A. 2017. Integrated organotypic slice cultures and RT-QuIC (OSCAR) assay: implications for translational discovery in protein misfolding diseases. Scientific Reports. 7:43155. doi:10.1038/srep43155.
Mammadova, N., Ghaisas, S., Zenitsky, G., Sakaguchi, D.S., Kanthasamy, A.G., Greenlee, J.J., West Greenlee, M.H. 2017. Lasting retinal injury in a mouse model of blast-induced trauma. American Journal of Pathology. 187(7):1459-1472. doi:10.1016/j.ajpath.2017.03.005.
FRIDAY, APRIL 20, 2018
*** Scrapie Transmits To Pigs By Oral Route, what about the terribly flawed USA tse prion feed ban?
Research Project: Pathobiology, Genetics, and Detection of Transmissible Spongiform Encephalopathies
Passage of scrapie to deer results in a new phenotype upon return passage to sheep
Research Project: Pathobiology, Genetics, and Detection of Transmissible Spongiform Encephalopathies
Location: Virus and Prion Research
Title: Passage of scrapie to deer results in a new phenotype upon return passage to sheep)
Author
item Greenlee, Justin
item Kokemuller, Robyn
item Moore, Sarah
item West Greenlee, N
Submitted to: Prion
Publication Type: Abstract Only
Publication Acceptance Date: 3/15/2017
Publication Date: N/A
Citation: N/A
Interpretive Summary:
Technical Abstract: Aims: We previously demonstrated that scrapie has a 100% attack rate in white-tailed deer after either intracranial or oral inoculation. Samples from deer that developed scrapie had two different western blot patterns: samples derived from cerebrum had a banding pattern similar to the scrapie inoculum, but samples from brainstem had a banding pattern similar to CWD. In contrast, transmission of CWD from white-tailed deer to sheep by the intracranial route has a low attack rate and to-date oronasal exposure has been unsuccessful. The purpose of this study was to determine if sheep are susceptible to oronasal exposure of the scrapie agent derived from white-tailed deer.
Methods: At approximately 5 months of age, Suffolk sheep of various PRNP genotypes were challenged by the oronasal route with 10% brain homogenate derived from either the cerebrum or the brainstem of scrapie-affected deer. Genotypes represented in each inoculation group were VV136RR154QQ171 (n=2), AA136RR154QQ171 (n=2), and AV136RR154QR171 (n=1). After inoculation, sheep were observed daily for clinical signs. Upon development of clinical signs, sheep were killed with an overdose of pentobarbital sodium and necropsied. Tissue samples were tested for the presence of PrPSc by EIA, western blot, and immunohistochemistry (IHC). The No. 13-7 scrapie inoculum used for the deer has a mean incubation period of 20.1 months in sheep with the AA136RR154QQ171 genotype and 26.7 months in sheep with the VV136RR154QQ171 genotype.
Results: Sheep inoculated oronasally with WTD derived scrapie developed disease, but only after inoculation with the inoculum from the cerebrum that had a scrapie-like profile. The first sheep to develop clinical signs at approximately 29 months post inoculation had the VV136RR154QQ171 genotype. Eventually sheep of the AA136RR154QQ171 genotype developed clinical signs, but at a mean incubation of 52 months. At 62 months post-inoculation, none of the sheep inoculated with material from the deer brainstem have developed clinical disease.
Conclusions: The No. 13-7 inoculum used in the original deer experiment readily infects white-tailed deer and sheep of various genotypes by the oronasal route. When inoculum is made from different brain regions of No 13-7 scrapie-infected deer from either cerebrum with a scrapie-like western blot pattern or brainstem with a CWD-like western blot pattern, sheep with the VV136RR154QQ171 genotype are the first to develop clinical signs. This is in contrast to the original No. 13-7 inoculum that has a faster incubation period in sheep with the AA136RR154QQ171 genotype. Similar to experiments conducted with CWD, sheep oronasally inoculated with brainstem material from deer with a CWD-like molecular profile have no evidence of disease after 62 months of incubation. While scrapie is not known to occur in free-ranging populations of white-tailed deer, experimental cases are difficult to differentiate from CWD. This work raises the potential concern that scrapie infected deer could serve as a confounding factor to scrapie eradication programs as scrapie from deer seems to be transmissible to sheep by the oronasal route.
Research Project: TRANSMISSION, DIFFERENTIATION, AND PATHOBIOLOGY OF TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES
Title: Transmission of the agent of sheep scrapie to deer results in PrPSc with two distinct molecular profiles Authors
item Greenlee, Justin item Moore, Sarah - item Smith, Jodi item West Greenlee, Mary - item Kunkle, Robert
Submitted to: Prion Publication Type: Abstract Only Publication Acceptance Date: March 31, 2015 Publication Date: May 25, 2015 Citation: Greenlee, J., Moore, S.J., Smith, J.., West Greenlee, M.H., Kunkle, R. 2015.
Scrapie transmits to white-tailed deer by the oral route and has a molecular profile similar to chronic wasting disease and distinct from the scrapie inoculum.
Prion 2015. p. S62.
Technical Abstract: The purpose of this work was to determine susceptibility of white-tailed deer (WTD) to the agent of sheep scrapie and to compare the resultant PrPSc to that of the original inoculum and chronic wasting disease (CWD). We inoculated WTD by a natural route of exposure (concurrent oral and intranasal (IN); n=5) with a US scrapie isolate. All scrapie-inoculated deer had evidence of PrPSc accumulation. PrPSc was detected in lymphoid tissues at preclinical time points, and deer necropsied after 28 months post-inoculation had clinical signs, spongiform encephalopathy, and widespread distribution of PrPSc in neural and lymphoid tissues. Western blotting (WB) revealed PrPSc with 2 distinct molecular profiles. WB on cerebral cortex had a profile similar to the original scrapie inoculum, whereas WB of brainstem, cerebellum, or lymph nodes reveal PrPSc with a higher profile resembling CWD. Homogenates with the 2 distinct profiles from WTD with clinical scrapie were further passaged to mice expressing cervid prion protein and intranasally to sheep and WTD. In cervidized mice, the two inocula have distinct incubation times. Sheep inoculated intranasally with WTD derived scrapie developed disease, but only after inoculation with the inoculum that had a scrapie-like profile. The WTD study is ongoing, but deer in both inoculation groups are positive for PrPSc by rectal mucosal biopsy.
In summary, this work demonstrates that WTD are susceptible to the agent of scrapie, two distinct molecular profiles of PrPSc are present in the tissues of affected deer, and inoculum of either profile type readily passes to deer.
Research Project: TRANSMISSION, DIFFERENTIATION, AND PATHOBIOLOGY OF TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES
Title: Scrapie transmits to white-tailed deer by the oral route and has a molecular profile similar to chronic wasting disease Authors
item Greenlee, Justin item Moore, S - item Smith, Jodi - item Kunkle, Robert item West Greenlee, M -
Submitted to: American College of Veterinary Pathologists Meeting Publication Type: Abstract Only Publication Acceptance Date: August 12, 2015 Publication Date: N/A
Technical Abstract: The purpose of this work was to determine susceptibility of white-tailed deer (WTD) to the agent of sheep scrapie and to compare the resultant PrPSc to that of the original inoculum and chronic wasting disease (CWD). We inoculated WTD by a natural route of exposure (concurrent oral and intranasal (IN); n=5) with a US scrapie isolate. All scrapie-inoculated deer had evidence of PrPSc accumulation. PrPSc was detected in lymphoid tissues at preclinical time points, and deer necropsied after 28 months post-inoculation had clinical signs, spongiform encephalopathy, and widespread distribution of PrPSc in neural and lymphoid tissues. Western blotting (WB) revealed PrPSc with 2 distinct molecular profiles. WB on cerebral cortex had a profile similar to the original scrapie inoculum, whereas WB of brainstem, cerebellum, or lymph nodes revealed PrPSc with a higher profile resembling CWD. Homogenates with the 2 distinct profiles from WTD with clinical scrapie were further passaged to mice expressing cervid prion protein and intranasally to sheep and WTD. In cervidized mice, the two inocula have distinct incubation times. Sheep inoculated intranasally with WTD derived scrapie developed disease, but only after inoculation with the inoculum that had a scrapie-like profile. The WTD study is ongoing, but deer in both inoculation groups are positive for PrPSc by rectal mucosal biopsy.
In summary, this work demonstrates that WTD are susceptible to the agent of scrapie, two distinct molecular profiles of PrPSc are present in the tissues of affected deer, and inoculum of either profile readily passes to deer.
*** 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.
White-tailed Deer are Susceptible to Scrapie by Natural Route of Infection
Jodi D. Smith, Justin J. Greenlee, and Robert A. Kunkle; Virus and Prion Research Unit, National Animal Disease Center, USDA-ARS
Interspecies transmission studies afford the opportunity to better understand the potential host range and origins of prion diseases. Previous experiments demonstrated that white-tailed deer are susceptible to sheep-derived scrapie by intracranial inoculation. The purpose of this study was to determine susceptibility of white-tailed deer to scrapie after a natural route of exposure. Deer (n=5) were inoculated by concurrent oral (30 ml) and intranasal (1 ml) instillation of a 10% (wt/vol) brain homogenate derived from a sheep clinically affected with scrapie. Non-inoculated deer were maintained as negative controls. All deer were observed daily for clinical signs. Deer were euthanized and necropsied when neurologic disease was evident, and tissues were examined for abnormal prion protein (PrPSc) by immunohistochemistry (IHC) and western blot (WB). One animal was euthanized 15 months post-inoculation (MPI) due to an injury. At that time, examination of obex and lymphoid tissues by IHC was positive, but WB of obex and colliculus were negative. Remaining deer developed clinical signs of wasting and mental depression and were necropsied from 28 to 33 MPI. Tissues from these deer were positive for scrapie by IHC and WB. Tissues with PrPSc immunoreactivity included brain, tonsil, retropharyngeal and mesenteric lymph nodes, hemal node, Peyer’s patches, and spleen. This work demonstrates for the first time that white-tailed deer are susceptible to sheep scrapie by potential natural routes of inoculation. In-depth analysis of tissues will be done to determine similarities between scrapie in deer after intracranial and oral/intranasal inoculation and chronic wasting disease resulting from similar routes of inoculation.
see full text ;
PO-039: A comparison of scrapie and chronic wasting disease in white-tailed deer
Justin Greenlee, Jodi Smith, Eric Nicholson US Dept. Agriculture; Agricultural Research Service, National Animal Disease Center; Ames, IA USA
White-tailed deer are susceptible to the agent of sheep scrapie by intracerebral inoculation
snip...
It is unlikely that CWD will be eradicated from free-ranging cervids, and the disease is likely to continue to spread geographically [10]. However, the potential that white-tailed deer may be susceptible to sheep scrapie by a natural route presents an additional confounding factor to halting the spread of CWD. This leads to the additional speculations that
1) infected deer could serve as a reservoir to infect sheep with scrapie offering challenges to scrapie eradication efforts and
2) CWD spread need not remain geographically confined to current endemic areas, but could occur anywhere that sheep with scrapie and susceptible cervids cohabitate.
This work demonstrates for the first time that white-tailed deer are susceptible to sheep scrapie by intracerebral inoculation with a high attack rate and that the disease that results has similarities to CWD. These experiments will be repeated with a more natural route of inoculation to determine the likelihood of the potential transmission of sheep scrapie to white-tailed deer. If scrapie were to occur in white-tailed deer, results of this study indicate that it would be detected as a TSE, but may be difficult to differentiate from CWD without in-depth biochemical analysis.
2012
PO-039: A comparison of scrapie and chronic wasting disease in white-tailed deer
Justin Greenlee, Jodi Smith, Eric Nicholson US Dept. Agriculture; Agricultural Research Service, National Animal Disease Center; Ames, IA USA
snip...
The results of this study suggest that there are many similarities in the manifestation of CWD and scrapie in WTD after IC inoculation including early and widespread presence of PrPSc in lymphoid tissues, clinical signs of depression and weight loss progressing to wasting, and an incubation time of 21-23 months. Moreover, western blots (WB) done on brain material from the obex region have a molecular profile similar to CWD and distinct from tissues of the cerebrum or the scrapie inoculum. However, results of microscopic and IHC examination indicate that there are differences between the lesions expected in CWD and those that occur in deer with scrapie: amyloid plaques were not noted in any sections of brain examined from these deer and the pattern of immunoreactivity by IHC was diffuse rather than plaque-like.
*** After a natural route of exposure, 100% of WTD were susceptible to scrapie.
Deer developed clinical signs of wasting and mental depression and were necropsied from 28 to 33 months PI. Tissues from these deer were positive for PrPSc by IHC and WB. Similar to IC inoculated deer, samples from these deer exhibited two different molecular profiles: samples from obex resembled CWD whereas those from cerebrum were similar to the original scrapie inoculum. On further examination by WB using a panel of antibodies, the tissues from deer with scrapie exhibit properties differing from tissues either from sheep with scrapie or WTD with CWD. Samples from WTD with CWD or sheep with scrapie are strongly immunoreactive when probed with mAb P4, however, samples from WTD with scrapie are only weakly immunoreactive. In contrast, when probed with mAb’s 6H4 or SAF 84, samples from sheep with scrapie and WTD with CWD are weakly immunoreactive and samples from WTD with scrapie are strongly positive. This work demonstrates that WTD are highly susceptible to sheep scrapie, but on first passage, scrapie in WTD is differentiable from CWD.
2011
*** After a natural route of exposure, 100% of white-tailed deer were susceptible to scrapie.
---end personal email---end...tss
Monday, August 6, 2012
TAFS BSE in USA August 6, 2012 BSE in USA
Saturday, May 2, 2009
APHIS AND WHO PLAN TO EXEMPT THE ATYPICAL SCRAPIE NOR-98 FROM REGULATIONS AT MEETING THIS MONTH
Monday, November 30, 2009
USDA AND OIE COLLABORATE TO EXCLUDE ATYPICAL SCRAPIE NOR-98 ANIMAL HEALTH CODE
Thursday, December 20, 2012
OIE GROUP RECOMMENDS THAT SCRAPE PRION DISEASE BE DELISTED AND SAME OLD BSe WITH BOVINE MAD COW DISEASE
Tuesday, July 2, 2013
APHIS USDA Administrator Message to Stakeholders: Agency Vision and Goals Eliminating ALL remaining BSE barriers to export market
The EFSA Panel on Biological Hazards recently published its conclusions on the scrapie situation in the EU after 10 years of monitoring and control of the disease in sheep and goats (EFSA 2014), and one of the most interesting findings was the Icelandic experience regarding the effect of disinfection in scrapie control. The Icelandic plan consisted of: culling scrapie-affected sheep or the whole flock in newly diagnosed outbreaks; deep cleaning and disinfection of stables, sheds, barns and equipment with high pressure washing followed by cleaning with 500 parts per million of hypochlorite; drying and treatment with 300 ppm of iodophor; and restocking was not permitted for at least two years. Even when all of these measures were implemented, scrapie recurred on several farms, indicating that the infectious agent survived for years in the environment, even as many as 16 years after restocking (Georgsson and others 2006).
Infectious agent of sheep scrapie may persist in the environment for at least 16 years
Gudmundur Georgsson,1 Sigurdur Sigurdarson2 and Paul Brown3
Correspondence
Gudmundur Georgsson ggeorgs@hi.is
1 Institute for Experimental Pathology, University of Iceland, Keldur v/vesturlandsveg, IS-112 Reykjavı´k, Iceland
2 Laboratory of the Chief Veterinary Officer, Keldur, Iceland
3 Bethesda, Maryland, USA
Received 7 March 2006 Accepted 6 August 2006
In 1978, a rigorous programme was implemented to stop the spread of, and subsequently eradicate, sheep scrapie in Iceland. Affected flocks were culled, premises were disinfected and, after 2–3 years, restocked with lambs from scrapie-free areas. Between 1978 and 2004, scrapie recurred on 33 farms. Nine of these recurrences occurred 14–21 years after culling, apparently as the result of environmental contamination, but outside entry could not always be absolutely excluded. Of special interest was one farm with a small, completely self-contained flock where scrapie recurred 18 years after culling, 2 years after some lambs had been housed in an old sheephouse that had never been disinfected. Epidemiological investigation established with near certitude that the disease had not been introduced from the outside and it is concluded that the agent may have persisted in the old sheep-house for at least 16 years.
21 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...
THURSDAY, NOVEMBER 01, 2018
National Scrapie Eradication Program September 2018 Monthly Report Fiscal Year 2018 October 15, 2018
FRIDAY, NOVEMBER 2, 2018
OIE Final Report Iceland Scrapie TSE Prion 02/11/2018 Start of Event 12/09/2018
MONDAY, JANUARY 28, 2019
Scrapie (Rida) Iceland Information received on 28/01/2019 from Dr Sigurborg Daðadóttir, Chief Veterinary Officer
***> USDA APHIS CDC FDA BSE CWD TSE PRION UPDATE 2019
THURSDAY, MARCH 14, 2019
USDA APHIS CDC FDA BSE TSE PRION UPDATE 2019
THURSDAY, MARCH 14, 2019
USDA APHIS CDC Cervids: Chronic Wasting Disease Specifics Updated 2019
FRIDAY, MARCH 15, 2019
Saskatchewan Chronic Wasting Disease TSE Prion 349 Cases Positive for 2018
FRIDAY, MARCH 15, 2019
USDA APHIS SCRAPIE TSE PRION Sheep and Goat Health Update 2019
WEDNESDAY, MAY 29, 2019
Incomplete inactivation of atypical scrapie following recommended autoclave decontamination procedures USDA HERE'S YOUR SIGN!
TUESDAY, JULY 16, 2019
Spain Bovine Spongiform Encephalopathy BSE TSE Prion July 5 2019
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
MONDAY, JUNE 24, 2019
APHIS, FSIS, USDA, FDA, Transmissible Spongiform Encephalopathy TSE, BSE, CWD, Scrapie, Camel TSE Prion Disease, CJD Humans
Terry S. Singeltary Sr.
posted by Terry S. Singeltary Sr. | 10:04 AM
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