Tuesday, July 15, 2014

Chronic wasting disease model of genetic selection favoring prolonged survival in Rocky Mountain elk (Cervus elaphus)

on a wing and a prayer, and over 100-year modeled timeframes...


Chronic wasting disease model of genetic selection favoring prolonged survival in Rocky Mountain elk (Cervus elaphus)




1Department of Veterinary Sciences, University of Wyoming, Laramie, Wyoming 82070 USA 2Wyoming Game and Fish Department, Thorne-Williams Wildlife Research Unit, Wheatland, Wyoming 82201 USA Citation: Williams, A. L., T. J. Kreeger, and B. A. Schumaker. 2014. Chronic wasting disease model of genetic selection favoring prolonged survival in Rocky Mountain elk (Cervus elaphus). Ecosphere 5(5):60. http://dx.doi.org/10.1890/ ES14-00013.1




As the area where chronic wasting disease (CWD) has been found continues to expand, there is concern over the impact it may have on elk (Cervus elaphus) populations that congregate on winter feedgrounds in Wyoming. A stochastic simulation model was created to determine the effect that genotype-specific CWD mortality rates had on a hypothetical free-ranging elk population. Life table data gathered from captive elk held in a CWD-contaminated facility was used to parameterize the model. Modeling the free-ranging elk herd without hunting or differences in survival by genotype resulted in a near extinction decrease in elk numbers over a 100-year period. However, incorporating differences in CWD-mortality by genotype into the model allowed the population to stabilize if hunting was modified to harvest only antlered elk. Our results indicate that, with flexible hunting management, elk populations could adapt to CWD through changes in the frequency of genotypes associated with the incubation time for CWD.




All possible levels of hunting were not analyzed.


An antlered-only management option that maintained current high levels of bull harvest caused a decrease in the population well below the population objective. However, the downward trend stabilized and suggested that if the time frame was drawn out, the population may begin to rebound. The antlered only strategy was included because it is one method that is highly likely to be incorporated in an area where the population is a concern to managers who want to continue hunting (Wyoming Game and Fish Department 2009). The model showed that in an environment without harvest, CWD was not limiting enough to keep this population from rising to higher than desired numbers (i.e., three times the proposed population objective of 1,900 elk; Wyoming Game and Fish Department 2012). Our models indicated that elk populations exposed to PrPCWD could respond through changes in frequency of genotypes with varying incubation times. Also, changes in hunting strategies of elk populations could help maintain numbers through these transitional periods. A reduction in hunting would likely be necessary; however, eliminating harvest of all elk would allow this population to exceed population objectives over time. Experimentation with hunting levels likely would be required to determine what level of elk harvest is most likely to maintain desired numbers. Additionally, monitoring genotypic frequencies in conjunction with fecundity and recruitment are highly warranted.


According to our models and assumptions and considering prolonged incubation times associated with certain genotypes, CWD alone was not enough to cause extinction of elk herds that congregate on winter feedgrounds. While CWD can negatively impact wildlife populations (Miller et al. 2008), our results indicated that, with flexible management, elk populations could adapt to CWD through increases in the frequency of genotypes over 100-year modeled timeframes.


Key words: Cervus elaphus; chronic wasting disease; elk; feedgrounds; genetics; model; prion; Wyoming, USA.



Article Citation: Lisa L. Wolfe, Karen A. Fox, and Michael W. Miller (2014)


“Atypical” Chronic Wasting Disease in PRNP Genotype 225FF Mule Deer.


Journal of Wildlife Diseases In-Press. doi: http://dx.doi.org/10.7589/2013-10-274


Ahead of Print “Atypical” Chronic Wasting Disease in PRNP Genotype 225FF Mule Deer Lisa L. Wolfe 1,2, Karen A. Fox 1, and Michael W. Miller 1 1 Colorado Division of Parks and Wildlife, Wildlife Research Center, 317 West Prospect Road, Fort Collins, Colorado 80526-2097, USA




We compared mule deer (Odocoileus hemionus) of two different PRNP genotypes (225SS, 225FF) for susceptibility to chronic wasting disease (CWD) in the face of environmental exposure to infectivity. All three 225SS deer had immunohistochemistry (IHC)-positive tonsil biopsies by 710 days postexposure (dpe), developed classic clinical signs by 723–1,200 dpe, and showed gross and microscopic pathology, enzyme-linked immunosorbent assay (ELISA) results, and IHC staining typical of prion disease in mule deer. In contrast, although all three 225FF deer also became infected, the two individuals surviving >720 dpe had consistently negative biopsies, developed more-subtle clinical signs of CWD, and died 924 or 1,783 dpe. The 225FF deer were “suspect” by ELISA postmortem but showed negative or equivocal IHC staining of lymphoid tissues; both clinically affected 225FF deer had spongiform encephalopathy in the absence of IHC staining in the brain tissue. The experimental cases resembled three cases encountered among five additional captive 225FF deer that were not part of our experiment but also died from CWD. Aside from differences in clinical disease presentation and detection, 225FF mule deer also showed other, more-subtle, atypical traits that may help to explain the rarity of this genotype in natural populations, even in the presence of enzootic CWD.


Key words: Chronic wasting disease, genotype, mule deer, Odocoileus hemionus, prion, PRNP


Received: October 21, 2013; Accepted: January 22, 2014 ;Published Online: May 7, 2014


2 Corresponding author (email: lisa.wolfe@state.co.us)



Immunity No immune response to the CWD prion protein has been detected.



Background: Transmissible spongiform encephalopathies (TSEs) are a group of related diseases that include Creutzfeldt-Jakob disease (CJD) and its new variant (vCJD), kuru, scrapie, bovine spongiform encephalopathy (BSE; “mad cow disease”), chronic wasting disease (CWD) in deer and elk, and others. These diseases have incubation periods of years or decades, cause progressive neurological degeneration, evoke no obvious immune response, and are invariably fatal.



Our earlier work demonstrated that elk with the prion genotype 132LL were underrepresented in infected elk *** although the genotype is not fully protective in captive elk. We have now demonstrated that the 132L allele extends the incubation time in elk, resulting in a doubling of the preclinical incubation period. This finding is important for regulatory agencies and producers in states in which clinical disease is considered in selection of animals for surveillance testing.


Further, although our earlier work demonstrated that elk with the prion genotype 132LL were underrepresented in infected elk, *** we confirmed one case of CWD in an elk of this genotype, demonstrating that these elk are not invariably resistant to disease.


However, we demonstrated that a relatively high percentage of elk with positive tests on brain tissue have negative tests of the retropharyngeal lymph node. Therefore, accurate diagnosis of elk requires examination of both the brain and the lymph node.


This report serves to document research conducted under a specific cooperative agreement between ARS and Colorado State University. Additional details of research can be found in the report for the parent project 5348-32000-021-00D Animal Health.



Research Project: TRANSMISSION, DIFFERENTIATION, AND PATHOBIOLOGY OF TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES Title: Prolonged CWD incubation time and unique PrP**d profile in Prnp 132LL elk




item Greenlee, Justin item O'Rourke, Katherine item Hamir, Amirali item Gidlewski, Thomas - USDA-VS-APHIS, FT COLLINS item Zhuang, Dongyue item Spraker, Terry - COLORADO STATE UNIVERSITY


Submitted to: United States Animal Health Association Proceedings Publication Type: Abstract Only Publication Acceptance Date: October 20, 2007 Publication Date: October 20, 2007 Repository URL: http://www.usaha.org/meetings/proceedings.shtml Citation: Greenlee, J.J., O'Rourke, K.I., Hamir, A.N., Gidlewski, T., Zhuang, D., Spraker, T. 2007. Prolonged CWD Incubation Time and Unique PrP**d Profile in Prnp 132LL Elk. In: Proceedings of the U.S. Animal Health Association 111th Annual Meeting, Captive Wildlife and Alternative Livestock Committee, October 20, 2007, Reno, Nevada. p. 264-265.


Technical Abstract:


The transmissible spongiform encephalopathies including chronic wasting disease (CWD) in deer and elk invariably result in fatal neurodegeneration and accumulation of PrP**d, an abnormal form of the host prion protein PrP**c. In some species, polymorphisms in the open reading frame of the Prnp gene are associated with differences in the manifestation of prion disease including relative susceptibility, clinical signs, incubation time, and neuropathology. The polymorphism (M to L) at Prnp 132 in Rocky Mountain Elk (Cervus elaphus nelsoni) corresponds to the human (M to V) polymorphism at Prnp 129, which has been associated with susceptibility to vCJD. Elk with 132 M alleles are predisposed to CWD and heterozygosity is associated with a prolonged incubation time following experimental challenge. Previous studies suggest that elk homozygous for 132 L occur rarely and make up the extreme minority of elk affected with CWD. The effect of the 132 LL genotype on the development of CWD post-exposure was previously unknown. The purpose of this study was to define the course of disease in elk with various Prnp 132 allele combinations. Elk (n=8; 2MM, 2LM, 4LL) were orally inoculated at 8 months of age with 15 ml of pooled brain homogenate from one 132 MM and one 132 LM elk. Elk were observed daily after inoculation and necropsies were done when clinical signs became unequivocal. Immunohistochemistry (IHC), western blot, and microscopic examination were used to confirm infection. Incubation time was dependent on genotype. Clinical signs were apparent in 132 MM elk after 23 months and 132 LM elk after 40 months. Rectal biopsies were done on the remaining 132 LL elk with 3 of 4 testing positive for PrP**d by IHC indicating peripheral distribution of PrP**d is apparent prior to the onset of clinical disease. Clinical signs were apparent in 132 LL elk after 59-63 months. One elk was euthanized 63 months post-inoculation without exhibiting clinical signs, but had PrP**d accumulation in CNS and peripheral lymphoid tissues. Differences between genotype were apparent after western blot analysis. The molecular weight of the proteinase K resistant bands of PrP**d is lower in the 132LL elk compared to 132MM or 132LM elk.


***In summary, LL elk are susceptible to CWD, but have a prolonged incubation time and western blot profile unique from other genotypes of elk with CWD. Additional studies are planned to determine the mechanisms responsible for the distinct presentation of CWD in 132 LL elk.



every time someone claims a certain species or type of species resistant to a TSE prion, years later they are proven wrong, as with the rabbit and the tse prion.




“Our results confirm previous studies shattering the myth that rabbits are resistant to prion infection and this should be taken into account when choosing protein sources to feed rabbits.”


THERE are many reasons in the cwd study quoted, why 41 percent percent tested negative, and them being resistant would be the last. it’s only wishful thinking folks, wishful thinking to dream that ;


‘’see a CWD-resistant deer herd as soon as 50 years’’ but dream on if you must $$$


there is nothing to date that is even close to producing any TSE prion free herd of any species, but yet some are willing to risk the entire Wisconsin deer herd on a whelm and a dream $$$ good luck with that. ...


If we let nature take its course, won’t deer become completely resistant to CWD?


Researchers have investigated for genetic resistance to this disease within white-tailed deer.


***Unfortunately, no white-tailed deer genotypes have been identified with complete resistance to CWD.


Researchers have found an uncommon genotype that appears to allow deer to survive longer with CWD than other genetic types, but they still eventually die from CWD. This research also implies that deer with this genotype also have more time to expose other healthy deer to CWD.





‘’Furthermore, the prevalence of the disease and risk factors are not well understood. According to CWD specialists, there is small hope that CWD will run its course and leave behind a generation of CWD resistant deer; *** however, many scientists do not believe this is the case for CWD.’’


P.159: Transgenic mice overexpressing rabbit prion protein are susceptible to BSE, BASE and scrapie prion strains but resistant to CWD and atypical scrapie


Natalia Fernández-Borges,1 Enric Vidal,2 Belén Pintado,4 Hasier Eraña,1 Montserrat Ordóñez,3 Mercedes Márquez,5 Francesca Chianini,6 Dolors Fondevila,5 Manuel A Sánchez-Martín,7 Olivier Andréoletti,8 Mark P Dagleish,6 Martí Pumarola,5 and Joaquín Castilla1,3 1CIC bioGUNE; Parque tecnológico de Bizkaia; Derio; Bizkaia, Spain; 2Centre de Recerca en Sanitat Animal (CReSA); UAB-IR TA, Campus de la Universitat Autònoma de Barcelona; Bellaterra; Barcelona, Catalonia, Spain; 3IKERBASQUE; Basque Foundation for Science; Bilbao, Bizkaia, Spain; 4Centro Nacional de Biotecnología (CNB), Campus de Cantoblanco; Cantoblanco; Madrid, Spain; 5Department of Animal Medicine and Surgery; Veterinary faculty; Universitat Autònoma de Barcelona (UAB); Bellaterra (Cerdanyola del Vallès); Barcelona, Catalonia, Spain; 6Moredun Research Institute; Bush Loan, Penicuik, Scotland, UK; 7Unidad de Generación de OMGs. S.E.A. Department of Medicine; University of Salamanca; Salamanca, Spain; 8Ecole Nationale du Veterinaire; Service de Pathologie du Bétail; Toulouse, France


Interspecies transmission of prions is a well established phenomenon, both experimentally and in field conditions. Upon passage through new hosts prion strains have proven their capacity to change their properties. It is, in fact, a source of strain diversity which needs to be considered when assessing the potential risks associated with consumption of prion contaminated protein sources.


Rabbits were considered for decades a prion resistant species until proven recently otherwise. To determine the extent of rabbit susceptibility to prions and to assess their effects on the passage of different prion strains through this species, a transgenic mouse model overexpressing rabbit PrPC was developed (TgRab). Intracerebral challenges with prion strains originating from a variety of species including field isolates (SSBP1 scrapie, Nor98-like scrapie, BSE, BASE and CWD), experimental murine strains (ME7 and RML), experimentally obtained strains (sheepBSE) and strains obtained by in vitro crossing of the species barrier using saPMCA (BSE-RabPrPres, SSBP1-RabPrPres and CWD-RabPrPres) have been performed.


Interestingly, on first passage, TgRab were susceptible to the majority of prions tested with the exception of SSBP1 scrapie, CWD and Nor98 scrapie. Furthermore TgRab were capable of propagating strain-specific features such as differences in incubation periods, brain lesion and PrPd deposition profiles and PK resistant western blotting band patterns. Our results confirm previous studies shattering the myth that rabbits are resistant to prion infection and this should be taken into account when choosing protein sources to feed rabbits.





Title: Resistance of fallow deer (dama dama) to chronic wasting disease under natural exposure in a heavily contaminated environment




item Rhyan, J - item Spraker, T - item Mccollum, M - item Nol, P - item Wolfe, L - item Miller, M - item Davis, T - item Creekmore, L - item O'Rourke, Katherine


Submitted to: Journal of Wildlife Diseases Publication Type: Peer Reviewed Journal Publication Acceptance Date: April 3, 2011 Publication Date: November 25, 2009 Citation: Rhyan, J.C., Spraker, T.R., Mccollum, M., Nol, P., Wolfe, L., Miller, M.W., Davis, T., Creekmore, L., Orourke, K.I. 2009. Resistance of fallow deer (dama dama) to chronic wasting disease under natural exposure in a heavily contaminated environment. Journal of Wildlife Diseases. 47(3):739-744.


Interpretive Summary: Chronic wasting disease or CWD is a fatal neurodegenerative disease of deer and elk in North America. The disease is a member of the prion family of disorders and is associated with misfolding of a normal host prion protein. Detection of the misfolded protein is a useful diagnostic test, particularly for animals in early disease. CWD has been diagnosed in wild mule deer (Odocoileus hemionus), white-tailed deer (O. virginianus), Rocky Mountain elk (Cervus elaphus), and Shira's moose (Alces alces). Disease outbreaks in farmed cervids in the US and Canada have demonstrated some differences in relative disease susceptibility associated with changes in the gene for the normal prion protein ***but no genotype has been linked to disease resistance. However, CWD has not been diagnosed in farmed fallow deer (Dama dama) on farms with infected deer or elk. Fallow deer are susceptible to direct inoculation of infected material into the brain, but the levels of abnormal prion protein in the experimentally infected fallow deer were low. In this study, we investigated the susceptibility of fallow deer to natural disease transmission by housing fallow deer for up to 7 years in pens with mule deer, a highly susceptible species showing strong evidence of prion shedding into the environment. There was no evidence of disease or abnormal prion protein in any of the fallow deer in this study. DNA analysis of the deer in the study demonstrated a naturally occurring genetic mutation that may confer resistance to CWD. If confirmed in follow up studies, fallow deer would be the first CWD resistant cervid species. Technical Abstract: Chronic wasting disease or CWD is a transmissible spongiform encephalopathy or prion disorder of cervid ruminants in several regions of the US and Canada. The prion disorders are characterized by misfolding of the host cellular prion protein into a relatively protease resistant and potentially neurotoxic disease-associated isoform. CWD is highly transmissible in mule deer (Odocoileus hemionus) with evidence for horizontal transmission and environmental persistence of the infectious agent in the environment. Examination of tissues from depopulated infected herds in the US and Canada has not yet shown evidence of CWD in farmed fallow deer (Dama dama), an imported species raised for meat, antlers, and exhibition purposes. In this study, fallow deer were held in pens with a succession of CWD-infected mule deer for 7 years. Mule deer losses were 100% during that time, with an average incubation time of less than 3 years. In spite of this persisent natural exposure, no evidence of abnormal prion protein was found in the tissues of the fallow deer following 7 years of exposure. Resistance to prion disease in sheep and possibly in goats in associated with single amino acid changes in the normal prion protein. All fallow deer examined to date are homozygous for asparagine (N) at residue 138. Mule deer, white-tailed deer, Rocky Mountain elk, and Shira's moose are all homozygous for serine (S) at that site, although the unexpressed cervid pseudogene encodes 138N. This finding represents the first possible evidence for genetic resistance to CWD in cervids.



***but no genotype has been linked to disease resistance.


*** This finding represents the first possible evidence for genetic resistance to CWD in cervids. ...NOT!!!




Experimental transmission of chronic wasting disease (CWD) from elk and white-tailed deer to fallow deer by intracerebral route: Final report


Amir N. Hamir, Justin J. Greenlee, Eric M. Nicholson, Robert A. Kunkle, Juergen A. Richt, Janice M. Miller, Mark Hall


Ab s t r a c t


Final observations on experimental transmission of chronic wasting disease (CWD) from elk (Cervus elaphus nelsoni) and whitetailed deer (Odocoileus virginianus) to fallow deer (Dama dama) are reported herein. During the 5-year study, 13 fawns were inoculated intracerebrally with CWD-infected brain material from white-tailed deer (n = 7; Group A) or elk (n = 6; Group B), and 3 other fawns were kept as uninoculated controls (Group C). As described previously, 3 CWD-inoculated deer were euthanized at 7.6 mo post-inoculation (MPI). None revealed presence of abnormal prion protein (PrPd) in their tissues. At 24 (Group A) and 26 (Group B) MPI, 2 deer were necropsied. Both animals had a small focal accumulation of PrPd in their midbrains. Between 29 and 37 MPI, 3 other deer (all from Group A) were euthanized. The 5 remaining deer became sick and were euthanized between 51 and 60 MPI (1 from Group A and 4 from Group B). Microscopic lesions of spongiform encephalopathy (SE) were observed in only these 5 animals; however, PrPd was detected in tissues of the central nervous system by immunohistochemistry, Western blot, and by commercial rapid test in all animals that survived beyond 24 MPI. This study demonstrates that intracerebrally inoculated fallow deer not only amplify CWD prions, but also develop lesions of spongiform encephalopathy.


Voluntary Report - public distribution Date: 6/17/2003 GAIN Report Number: E23101 E23101 European Union Sanitary/Phytosanitary/Food Safety Chronic Wasting Disease 2003


Approved by: Justina Torry U.S. Mission to the European Union, Brussels Prepared by: Sandie Kipe


Report Highlights: On March 7, 2003 the Scientific Steering Committee (SSC) of the European Commission Health and Consumer Protection Directorate General issued an opinion on Chronic Wasting Disease. However, the United States currently does not export significant quantities of live deer to the EU.


Includes PSD Changes: No Includes Trade Matrix: No Unscheduled Report Brussels USEU [BE2] [E2]


Summary On March 7, 2003 the Scientific Steering Committee (SSC) of the European Commission Health and Consumer Protection Directorate General the issued an opinion on Chronic Wasting Disease.


The opinion indicates that the early and widespread involvement of tissues in CWD infected animals does not allow the definition of a specified risk material list. However, due to the theoretical possibility of transmission to humans, livestock, or other domestic animals, the SSC concludes that it is important to ensure that no infectivity to the EU occurs through trade in live cervids. Currently, exports to the EU of deer and deer products are minimal.


Background Chronic wasting disease is predominately found in deer, and is caused by protein prions in the brain that are malformed. The malformed prion protein becomes a pathogen capable of killing the diseased animal. The pathogen peppers neutral tissue full of microscopic holes and gums up the brain with toxic clumps of protein called amyloid plaques, eventually causing enough damage to kill the animal. The malformed prion is extremely resistant, requiring extensive heating or corrosive chemicals to disinfect the prion.


CWD is in the same family as better-known bovine spongiform encepalopathy (BSE), or mad cow disease. BSE was spread by animal based feed inadvertently containing tissue from sick cows and sheep in the early 1980s in the U.K. BSE continues to persist in the U.K. but at a lower level relative to the earlier outbreak. In 1996 scientists realized that BSE could pass to humans who have consumed infected meat, leading to the fatal condition of Crueutzfeldt-Jakob disease (vCJD).


Researchers are currently working to determine if CWD could infect humans. A test tube study mixed CWD prions with healthy prions from cervids, humans, cows, and sheep. The CWD prions did have difficulty converting normal human prion proteins; only less than 7 percent were changed. However, this rate is relatively the same as that of BSE, which is known to affect humans leaving researchers to conclude that CWD may pose a similar health risk to humans.


The SSC report states that the disease is easily communicable from deer to deer, in experimental studies oral exposure to only small dosages resulted in infection. No practical live test exists to check whether an apparently healthy wild animal is infected with CWD, only a brain sample test can determine if CWD is present. Furthermore, the prevalence of the disease and risk factors are not well understood. According to CWD specialists, there is small hope that CWD will run its course and leave behind a generation of CWD resistant deer; ***however, many scientists do not believe this is the case for CWD.


During the March 6-7 meeting of the SSC, the recommendation was issued that no live cervids from North America be imported into Europe, since it is still unknown if the disease can spread to humans, livestock, or other domesticated animals. The SSC also recommended that a surveillance program is necessary to monitor any possible occurrence of CWD in Europe.


The full opinion may be viewed at:


Visit our website: our website www.useu.be/agri/usda.html provides a broad range of useful information on EU import rules and food laws and allows easy access to USEU reports, trade information and other practical information. More information on animal diseases can be found at http://www.fas.usda.gov/dlp/BSE/bse.html. E-mail: AgUSEUBrussels@fas.usda.gov


Related reports from USEU Brussels:


Report Number Title Date Released E23012 EU Veterinary Legislation Guide 01/28/2003





Classic Scrapie in Sheep with the ARR/ARR Prion Genotype in Germany and France


Martin H. Groschup,*1 Caroline Lacroux,†1 Anne Buschmann,* Gesine Lühken,‡ Jacinthe Mathey,† Martin Eiden,* Séverine Lugan,† Christine Hoffmann,* Juan Carlos Espinosa,§ Thierry Baron,¶ Juan Maria Torres,§ Georg Erhardt,‡ and Olivier Andreoletti†


In the past, natural scrapie and bovine spongiform encephalopathy (BSE) infections have essentially not been diagnosed in sheep homozygous for the A136R154R171 haplotype of the prion protein. This genotype was therefore assumed to confer resistance to BSE and classic scrapie under natural exposure conditions. Hence, to exclude prions from the human food chain, massive breeding efforts have been undertaken in the European Union to amplify this gene. We report the identifi cation of 2 natural scrapie cases in ARR/ARR sheep that have biochemical and transmission characteristics similar to cases of classic scrapie, although the abnormally folded prion protein (PrPSc) was associated with a lower proteinase-K resistance. PrPSc was clearly distinct from BSE prions passaged in sheep and from atypical scrapie prions. These findings strongly support the idea that scrapie prions are a mosaic of agents, which harbor different biologic properties, rather than a unique entity.




The discovery of these 2 cases clearly indicates that the genetic resistance of ARR/ARR sheep to the so-called clas-


sic scrapie agent is not absolute. It also provides evidence that, rather than being a single entity, scrapie is a mosaic of infectious agents harboring different biologic properties in its natural host....



A ProMED-mail post


ProMED-mail is a program of the International Society for Infectious Diseases


[1] Date: Fri 12 Mar 2010 Source: The Australian [edited]


A West Australian sheep has been found to have signs characteristic of the fatal brain disease atypical scrapie. It comes as Australia faces growing anger from its trade partners over the Rudd government's surprise decision to extend a ban on the importation of beef from countries exposed to mad cow disease for a further 2 years.


Australia's chief veterinarian, Andy Carroll, told the ABC an indicative case of the atypical scrapie had been confirmed but said it posed no risk to human or animal health or the safety of eating meat and animal products.


Nor does atypical scrapie carry the dire trade consequences associated with classical scrapie.


Classical scrapie is in the same transmissible spongiform encephalopathies (TSE) family as BSE, better known as mad cow disease, from which humans can be fatally infected.


Dr Carroll said samples from the sheep's brain were being sent to the World Reference Laboratory in Britain.


Neither atypical scrapie nor classical scrapie has been seen in Australia before, but a sheep in New Zealand tested positive to the atypical form last year [2009].


Atypical scrapie is a relatively recently discovered disease and the common scientific view is that it occurs spontaneously or naturally in very small numbers of older sheep in countries all over the world.


[Byline: Jodie Minus]


-- Communicated by: Sabine Zentis Castleview Pedigree English Longhorns Gut Laach 52385 Nideggen Germany


****** [2] Date: Wed 10 Mar 2010 Source: ABC News (Australian Broadcasting Corporation) [edited]


Animal health authorities are testing a sheep's brain for what could be Australia's 1st case of the disease atypical scrapie.


Although not confirmed, the sheep is thought to be from Western Australia.


This type of scrapie is described as a sporadic degenerative brain condition affecting older sheep, and is not contagious.


Ed Klim, from national advisory group SafeMeat, says a 2nd round of testing is now taking place. "We've been made aware that the Australian Animal Health Laboratory is conducting further routine testing on a sheep sample," he says.


"The disease isn't considered a health risk nor should have any impact on food safety or export markets for sheep meat of live sheep."


Australia's chief veterinarian and WA's Department of Agriculture of Food are both aware of the testing but will not comment.


-- Communicated by: Terry S Singeltary Sr


[Although atypical scrapie is not yet ruled out, it is important to realize this is a type of scrapie that thus far has only tended to appear as a sporadic condition in older animals. Currently it has not been shown to follow the same genetic tendencies for propagation as the usual scrapie.


However, the atypical phenotypic appearance has been shown to be preserved on experimental passage.


Atypical scrapie was first identified in Norwegian sheep in 1998 and has subsequently been identified in many countries, as Australia may join that list. It is likely that this case will be sent to the UK for definitive conformation.


[Ref: M Simmons, T Konold, L Thurston, et al. BMC Veterinary Research 2010, 6:14 [provisional abstract available at ]


"Background ----------- "Retrospective studies have identified cases predating the initial identification of this form of scrapie, and epidemiological studies have indicated that it does not conform to the behaviour of an infectious disease, giving rise to the hypothesis that it represents spontaneous disease. However, atypical scrapie isolates have been shown to be infectious experimentally, through intracerebral inoculation in transgenic mice and sheep. [Many of the neurological diseases can be transmitted by intracerebral inoculation, which causes this moderator to approach intracerebral studies as a tool for study, but not necessarily as a direct indication of transmissibility of natural diseases. - Mod.TG]


"The 1st successful challenge of a sheep with 'field' atypical scrapie from an homologous donor sheep was reported in 2007.


"Results -------- "This study demonstrates that atypical scrapie has distinct clinical, pathological, and biochemical characteristics which are maintained on transmission and sub-passage, and which are distinct from other strains of transmissible spongiform encephalopathies in the same host genotype.


"Conclusions ------------ Atypical scrapie is consistently transmissible within AHQ homozygous sheep, and the disease phenotype is preserved on sub-passage."


Lastly, this moderator wishes to thank Terry Singletary for some of his behind the scenes work of providing citations and references for this posting. - Mod.TG]


The HealthMap/ProMED-mail interactive map of Australia is available at . - Sr.Tech.Ed.MJ]



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.




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



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.







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)




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









*** FINALLY, in making such absolute statements such as any species being absolutely resistant to TSE prion disease, without final proof, I remind you of ;


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.







never say never in relations to TSE prion disease. ...TSS


Implications and Opportunities for Future Research Disease risk. There is much debate over whether a partial genetic resistance to CWD infection, or delayed progression, might have positive or negative effects on disease dynamics on the landscape. On the one hand, CWD infection rates may be substantially lower in some genotypes, reducing the prevalence of CWD and disease impacts on the affected population. These less-susceptible genotypes may gain a survival advantage over other genotypes.20 Yet, because the infectious state may be prolonged, these animals could disproportionately contribute to environmental contamination and transmission to susceptible animals.18,81 Future research is needed to determine whether all genotypes shed infectious material at similar rates. We currently understand little about the relative importance of direct vs. environmental routes of transmission in wild cervid populations. It will be important to understand the ways in which these routes interact with Prnp types to influence CWD infection and progression of disease. In addition to the mode of contact, the biological source of infectious material may have an impact on infectivity. It is unknown whether cervid species have different sensitivities to particular agent conformations, genotypes or strains. Additionally, though we know that cross-species infection is possible between elk, mule deer and white-tailed deer, we do not understand the level of transmissibility of agent between these species, or to other mammals in the ecosystem.82 Newly developed laboratory methods including PMCA,27,83 shaking assays,84 and cell-free conversions32 may provide insights on this question.




Survival and selection. The survival advantage conferred by decreased CWD susceptibility can be sufficient to alter population dynamics and provide selective pressure favoring disease resistance (demonstrated for the 96S allele in white-tailed deer, in press20). Such selective pressure is rarely measurable in wild populations, and indicates the potential for CWD to impact cervid populations. Additional genetic work will be needed to evaluate potential selective pressure on other loci and in other species to understand future trends in CWD epidemics and deer populations. Further, we currently lack information about nondisease related fitness characteristics associated with Prnp genetics. This is fertile ground for future selection studies. Future research such as simulation modeling might be used to address questions of how selective pressure could change as disease prevalence alters infection hazard, as agent strains shift, or how animal movement affects disease dynamics in wildlife populations.










Conclusions. To our knowledge, this is the first established experimental model of CWD in TgSB3985. We found evidence for co-existence or divergence of two CWD strains adapted to Tga20 mice and their replication in TgSB3985 mice. Finally, we observed phenotypic differences between cervid-derived CWD and CWD/Tg20 strains upon propagation in TgSB3985 mice. Further studies are underway to characterize these strains.


We conclude that TSE infectivity is likely to survive burial for long time periods with minimal loss of infectivity and limited movement from the original burial site. However PMCA results have shown that there is the potential for rainwater to elute TSE related material from soil which could lead to the contamination of a wider area. These experiments reinforce the importance of risk assessment when disposing of TSE risk materials.


The results show that even highly diluted PrPSc can bind efficiently to polypropylene, stainless steel, glass, wood and stone and propagate the conversion of normal prion protein. For in vivo experiments, hamsters were ic injected with implants incubated in 1% 263K-infected brain homogenate. Hamsters, inoculated with 263K-contaminated implants of all groups, developed typical signs of prion disease, whereas control animals inoculated with non-contaminated materials did not.


Our data establish that meadow voles are permissive to CWD via peripheral exposure route, suggesting they could serve as an environmental reservoir for CWD. Additionally, our data are consistent with the hypothesis that at least two strains of CWD circulate in naturally-infected cervid populations and provide evidence that meadow voles are a useful tool for CWD strain typing.


Conclusion. CWD prions are shed in saliva and urine of infected deer as early as 3 months post infection and throughout the subsequent >1.5 year course of infection. In current work we are examining the relationship of prionemia to excretion and the impact of excreted prion binding to surfaces and particulates in the environment.


Conclusion. CWD prions (as inferred by prion seeding activity by RT-QuIC) are shed in urine of infected deer as early as 6 months post inoculation and throughout the subsequent disease course. Further studies are in progress refining the real-time urinary prion assay sensitivity and we are examining more closely the excretion time frame, magnitude, and sample variables in relationship to inoculation route and prionemia in naturally and experimentally CWD-infected cervids.


Conclusions. Our results suggested that the odds of infection for CWD is likely controlled by areas that congregate deer thus increasing direct transmission (deer-to-deer interactions) or indirect transmission (deer-to-environment) by sharing or depositing infectious prion proteins in these preferred habitats. Epidemiology of CWD in the eastern U.S. is likely controlled by separate factors than found in the Midwestern and endemic areas for CWD and can assist in performing more efficient surveillance efforts for the region.


Conclusions. During the pre-symptomatic stage of CWD infection and throughout the course of disease deer may be shedding multiple LD50 doses per day in their saliva. CWD prion shedding through saliva and excreta may account for the unprecedented spread of this prion disease in nature.



see full text and more ;



Monday, June 23, 2014






Thursday, July 03, 2014


How Chronic Wasting Disease is affecting deer population and what’s the risk to humans and pets?




Tuesday, July 01, 2014






Monday, June 23, 2014






Sunday, June 29, 2014


Transmissible Spongiform Encephalopathy TSE Prion Disease North America 2014







Post a Comment

Subscribe to Post Comments [Atom]

<< Home