Unraveling the key to the resistance of canids to prion diseases
This is an uncorrected proof.
EP-021 Canine Prions: A New Form of Prion Disease
Mourad Tayebi1, Monique A David2, Brian Summers3
1 University of Melbourne, Veterinary Sciences, Australia; 2Ausbiologics, Sydney, Australia; 3Royal Veterinary College, London, UK
The origin of bovine spongiform encephalopathy (BSE), which rapidly evolved into a major epidemic remains unresolved and was initially widely attributed to transmission of sheep scrapie to cattle with contaminated feed prepared from rendered sheep carcasses. Alternative transmission hypotheses also include feed contaminated with unrecognized subclinical case(s) of bovine prion disease or with prion-infected human remains. However, following the demonstration of a BSE case exhibiting the novel mutation E211 K, similar to the E200K mutation associated with most genetic CJD in humans, support for a genetic origin of prion disease in cattle is gaining momentum. In contrast to other animal species such as feline, the canine species seems to be resistant to prion disease as no canine prion cases were previously reported.
We describe here three cases of Rottweiler puppy (called RWD cases) with neurological deficits and spongiform change. We used animal bioassays and in vitro studies to show efficient interspecies transmission of this novel canidae prion isolate to other species.
Biochemical studies revealed the presence of partially proteinase K (PK)-resistant fragment and immunohistochemistry displayed staining for PrPSc in the cerebral cortex. Importantly, interspecies transmission of canine PrPSc derived from RWD3 brain homogenates following inoculation of hamsters led to signs of prion disease and replication of PrPSc in brains, spinal cords and spleens of these animals.
These findings if confirmed by further cases of prion disease in canidae and regardless of the origin of the disease would have a major impact on animal and public health.
PRION 2016 TOKYO
OR-09: Canine spongiform encephalopathy—A new form of animal prion disease
Monique David, Mourad Tayebi UT Health; Houston, TX USA
It was also hypothesized that BSE might have originated from an unrecognized sporadic or genetic case of bovine prion disease incorporated into cattle feed or even cattle feed contaminated with prion-infected human remains.1 However, strong support for a genetic origin of BSE has recently been demonstrated in an H-type BSE case exhibiting the novel mutation E211K.2 Furthermore, a specific prion protein strain causing BSE in cattle is believed to be the etiological agent responsible for the novel human prion disease, variant Creutzfeldt-Jakob disease (vCJD).3 Cases of vCJD have been identified in a number countries, including France, Italy, Ireland, the Netherlands, Canada, Japan, US and the UK with the largest number of cases. Naturally occurring feline spongiform encephalopathy of domestic cats4 and spongiform encephalopathies of a number of zoo animals so-called exotic ungulate encephalopathies5,6 are also recognized as animal prion diseases, and are thought to have resulted from the same BSE-contaminated food given to cattle and humans, although and at least in some of these cases, a sporadic and/or genetic etiology cannot be ruled out. The canine species seems to display resistance to prion disease and no single case has so far been reported.7,8
Here, we describe a case of a 9 week old male Rottweiler puppy presenting neurological deficits; and histological examination revealed spongiform vacuolation characteristic of those associated with prion diseases.9 Initial biochemical studies using anti-PrP antibodies revealed the presence of partially proteinase K-resistant fragment by western blotting. Furthermore, immunohistochemistry revealed spongiform degeneration consistent with those found in prion disease and displayed staining for PrPSc in the cortex.
Of major importance, PrPSc isolated from the Rottweiler was able to cross the species barrier transmitted to hamster in vitro with PMCA and in vivo (one hamster out of 5). Futhermore, second in vivo passage to hamsters, led to 100% attack rate (n = 4) and animals displayed untypical lesional profile and shorter incubation period.
In this study, we show that the canine species might be sensitive to prion disease and that PrPSc isolated from a dog can be transmitted to dogs and hamsters in vitro using PMCA and in vivo to hamsters.
If our preliminary results are confirmed, the proposal will have a major impact on animal and public health and would certainly lead to implementing new control measures for ‘canine spongiform encephalopathy’ (CSE).
1. Colchester AC, Colchester NT. The origin of bovine spongiform encephalopathy: the human prion disease hypothesis. Lancet 2005; 366:856-61; PMID:16139661; http:// dx.doi.org/10.1016/S0140-6736(05)67218-2.
2. Richt JA, Hall SM. BSE case associated with prion protein gene mutation. PLoS Pathog 2008; 4:e1000156; PMID:18787697; http://dx.doi.org/10.1371/journal. ppat.1000156.
3. Collinge J. Human prion diseases and bovine spongiform encephalopathy (BSE). Hum Mol Genet 1997; 6:1699-705; PMID:9300662; http://dx.doi.org/10.1093/ hmg/6.10.1699.
4. Wyatt JM, Pearson GR, Smerdon TN, Gruffydd-Jones TJ, Wells GA, Wilesmith JW. Naturally occurring scrapie-like spongiform encephalopathy in five domestic cats. Vet Rec 1991; 129:233-6; PMID:1957458; http://dx.doi.org/10.1136/vr.129.11.233.
5. Jeffrey M, Wells GA. Spongiform encephalopathy in a nyala (Tragelaphus angasi). Vet Pathol 1988; 25:398-9; PMID:3232315; http://dx.doi.org/10.1177/030098588802500514.
6. Kirkwood JK, Wells GA, Wilesmith JW, Cunningham AA, Jackson SI. Spongiform encephalopathy in an arabian oryx (Oryx leucoryx) and a greater kudu (Tragelaphus strepsiceros). Vet Rec 1990; 127:418-20; PMID:2264242.
7. Bartz JC, McKenzie DI, Bessen RA, Marsh RF, Aiken JM. Transmissible mink encephalopathy species barrier effect between ferret and mink: PrP gene and protein analysis. J Gen Virol 1994; 75:2947-53; PMID:7964604; http://dx.doi.org/10.1099/0022-1317- 75-11-2947.
8. Lysek DA, Schorn C, Nivon LG, Esteve-Moya V, Christen B, Calzolai L, et al. Prion protein NMR structures of cats, dogs, pigs, and sheep. Proc Natl Acad Sci U S A 2005; 102:640-5; PMID:15647367; http://dx.doi.org/10.1073/pnas.0408937102.
9. Budka H. Neuropathology of prion diseases. Br Med Bull 2003; 66:121-30; PMID:14522854; http://dx.doi.org/10.1093/bmb/66.1.121.
Strain characteristics of the in vitro-adapted rabbit and dog BSE agent remained invariable with respect to the original cattle BSE prion, suggesting that the naturally low susceptibility of rabbits and dogs to prion infections should not alter their zoonotic potential if these animals became infected with BSE.
Neurobiology of Disease
Bovine Spongiform Encephalopathy Induces Misfolding of Alleged Prion-Resistant Species Cellular Prion Protein without Altering Its Pathobiological Features
Enric Vidal3, Natalia Fernández-Borges1, Belén Pintado4, Montserrat Ordóñez3, Mercedes Márquez6, Dolors Fondevila5,6, Juan María Torres7, Martí Pumarola5,6, and Joaquín Castilla1,2 + Author Affiliations
1CIC bioGUNE, 48160 Derio, Bizkaia, Spain,
2IKERBASQUE, Basque Foundation for Science, 48011 Bilbao, Bizkaia, Spain,
3Centre de Recerca en Sanitat Animal, Campus de la Universitat Autònoma de Barcelona (UAB)-IRTA, 08193 Bellaterra, Barcelona, Spain,
4Centro Nacional de Biotecnología, Campus de Cantoblanco, 28049 Cantoblanco, Madrid, Spain,
5Department of Animal Medicine and Surgery, Veterinary Faculty, UAB, 08193 Bellaterra (Cerdanyola del Vallès), Barcelona, Spain,
6Murine Pathology Unit, Centre de Biotecnologia Animal i Teràpia Gènica, UAB, 08193 Bellaterra (Cerdanyola del Vallès), Barcelona, Spain, and
7Centro de Investigación en Sanidad Animal-Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria, 28130 Valdeolmos, Madrid, Spain
Author contributions: E.V., N.F.-B., and J.C. designed research; E.V., N.F.-B., B.P., M.O., M.M., D.F., and J.C. performed research; E.V., N.F.-B., B.P., and J.C. contributed unpublished reagents/analytic tools; E.V., N.F.-B., B.P., M.O., M.M., D.F., J.M.T., M.P., and J.C. analyzed data; E.V. and J.C. wrote the paper.
Bovine spongiform encephalopathy (BSE) prions were responsible for an unforeseen epizootic in cattle which had a vast social, economic, and public health impact. This was primarily because BSE prions were found to be transmissible to humans. Other species were also susceptible to BSE either by natural infection (e.g., felids, caprids) or in experimental settings (e.g., sheep, mice). However, certain species closely related to humans, such as canids and leporids, were apparently resistant to BSE. In vitro prion amplification techniques (saPMCA) were used to successfully misfold the cellular prion protein (PrPc) of these allegedly resistant species into a BSE-type prion protein. The biochemical and biological properties of the new prions generated in vitro after seeding rabbit and dog brain homogenates with classical BSE were studied. Pathobiological features of the resultant prion strains were determined after their inoculation into transgenic mice expressing bovine and human PrPC. Strain characteristics of the in vitro-adapted rabbit and dog BSE agent remained invariable with respect to the original cattle BSE prion, suggesting that the naturally low susceptibility of rabbits and dogs to prion infections should not alter their zoonotic potential if these animals became infected with BSE. This study provides a sound basis for risk assessment regarding prion diseases in purportedly resistant species.
Received January 18, 2013. Revision received March 7, 2013. Accepted March 23, 2013. Copyright © 2013 the authors 0270-6474/13/337778-09$15.00/0
Friday, March 8, 2013
Dogs may have been used to make Petfood and animal feed
Monday, March 26, 2012
CANINE SPONGIFORM ENCEPHALOPATHY: A NEW FORM OF ANIMAL PRION DISEASE
Monday, February 14, 2011
THE ROLE OF PREDATION IN DISEASE CONTROL: A COMPARISON OF SELECTIVE AND NONSELECTIVE REMOVAL ON PRION DISEASE DYNAMICS IN DEER
NO, NO, NOT NO, BUT HELL NO !
Journal of Wildlife Diseases, 47(1), 2011, pp. 78-93 © Wildlife Disease Association 2011
Monday, March 8, 2010
Canine Spongiform Encephalopathy aka MAD DOG DISEASE
*** DEFRA TO SINGELTARY ON HOUND STUDY AND BSE 2001 ***
DEFRA Department for Environment, Food & Rural Affairs
Area 307, London, SW1P 4PQ Telephone: 0207 904 6000 Direct line: 0207 904 6287 E-mail: h.mcdonagh.defra.gsi.gov.uk
Mr T S Singeltary P.O. Box 42 Bacliff Texas USA 77518
21 November 2001
Dear Mr Singeltary
TSE IN HOUNDS
Thank you for e-mail regarding the hounds survey. I am sorry for the long delay in responding.
As you note, the hound survey remains unpublished. However the Spongiform Encephalopathy Advisory Committee (SEAC), the UK Government's independent Advisory Committee on all aspects related to BSE-like disease, gave the hound study detailed consideration at their meeting in January 1994. As a summary of this meeting published in the BSE inquiry noted, the Committee were clearly concerned about the work that had been carried out, concluding that there had clearly been problems with it, particularly the control on the histology, and that it was more or less inconclusive. However was agreed that there should be a re-evaluation of the pathological material in the study.
Later, at their meeting in June 95, The Committee re-evaluated the hound study to see if any useful results could be gained from it. The Chairman concluded that there were varying opinions within the Committee on further work. It did not suggest any further transmission studies and thought that the lack of clinical data was a major weakness.
Overall, it is clear that SEAC had major concerns about the survey as conducted. As a result it is likely that the authors felt that it would not stand up to r~eer review and hence it was never published. As noted above, and in the detailed minutes of the SEAC meeting in June 95, SEAC considered whether additional work should be performed to examine dogs for evidence of TSE infection. Although the Committee had mixed views about the merits of conducting further work, the Chairman noted that when the Southwood Committee made their recommendation to complete an assessment of possible spongiform disease in dogs, no TSEs had been identified in other species and hence dogs were perceived as a high risk population and worthy of study. However subsequent to the original recommendation, made in 1990, a number of other species had been identified with TSE ( e.g. cats) so a study in hounds was less
critical. For more details see- http://www.bseinquiry.gov.uk/files/yb/1995/06/21005001.pdf
As this study remains unpublished, my understanding is that the ownership of the data essentially remains with the original researchers. Thus unfortunately, I am unable to help with your request to supply information on the hound survey directly. My only suggestion is that you contact one of the researchers originally involved in the project, such as Gerald Wells. He can be contacted at the following address.
Dr Gerald Wells, Veterinary Laboratories Agency, New Haw, Addlestone, Surrey, KT 15 3NB, UK
You may also wish to be aware that since November 1994 all suspected cases of spongiform encephalopathy in animals and poultry were made notifiable. Hence since that date there has been a requirement for vets to report any suspect SE in dogs for further investigation. To date there has never been positive identification of a TSE in a dog.
I hope this is helpful
Yours sincerely 4
HUGH MCDONAGH BSE CORRESPONDENCE SECTION
I am sorry, but I really could have been a co-signatory of Gerald's minute.
I do NOT think that we can justify devoting any resources to this study, especially as larger and more important projects such as the pathogenesis study will be quite demanding.
If there is a POLITICAL need to continue with the examination of hound brains then it should be passed entirely to the VI Service.
J W WILESMITH Epidemiology Unit 18 October 1991
Mr. R Bradley
cc: Mr. G A H Wells
see new url;
3.3. Mr R J Higgins in conjunction with Mr G A Wells and Mr A C Scott would by the end of the year, indentify the three brains that were from the ''POSITIVE'' end of the lesion spectrum.
see new url;
TSE in dogs have not been documented simply because OF THE ONLY STUDY, those brain tissue samples were screwed up too. see my investigation of this here, and to follow, later follow up, a letter from defra, AND SEE SUSPICIOUS BRAIN TISSUE SAF's. ...TSS
TSE & HOUNDS
GAH WELLS (very important statement here...TSS)
AS implied in the Inset 25 we must not _ASSUME_ that transmission of BSE to other species will invariably present pathology typical of a scrapie-like disease.
76 pages on hound study;
The spongiform changes were not pathognomonic (ie. conclusive proof) for prion disease, as they were atypical, being largely present in white matter rather than grey matter in the brain and spinal cord. However, Tony Scott, then head of electron microscopy work on TSEs, had no doubt that these SAFs were genuine and that these hounds therefore must have had a scrapie-like disease. I reviewed all the sections myself (original notes appended) and although the pathology was not typical, I could not exclude the possibility that this was a scrapie-like disorder, as white matter vacuolation is seen in TSEs and Wallerian degeneration was also present in the white matter of the hounds, another feature of scrapie.
38.I reviewed the literature on hound neuropathology, and discovered that micrographs and descriptive neuropathology from papers on 'hound ataxia' mirrored those in material from Robert Higgins' hound survey. Dr Tony Palmer (Cambridge) had done much of this work, and I obtained original sections from hound ataxia cases from him. This enabled me provisionally to conclude that Robert Higgins had in all probability detected hound ataxia, but also that hound ataxia itself was possibly a TSE. Gerald Wells confirmed in 'blind' examination of single restricted microscopic fields that there was no distinction between the white matter vacuolation present in BSE and scrapie cases, and that occurring in hound ataxia and the hound survey cases.
39.Hound ataxia had reportedly been occurring since the 1930's, and a known risk factor for its development was the feeding to hounds of downer cows, and particularly bovine offal. Circumstantial evidence suggests that bovine offal may also be causal in FSE, and TME in mink. Despite the inconclusive nature of the neuropathology, it was clearly evident that this putative canine spongiform encephalopathy merited further investigation.
40.The inconclusive results in hounds were never confirmed, nor was the link with hound ataxia pursued. I telephoned Robert Higgins six years after he first sent the slides to CVL. I was informed that despite his submitting a yearly report to the CVO including the suggestion that the hound work be continued, no further work had been done since 1991. This was surprising, to say the very least.
41.The hound work could have provided valuable evidence that a scrapie-like agent may have been present in cattle offal long before the BSE epidemic was recognised. The MAFF hound survey remains unpublished.
Histopathological support to various other published MAFF experiments
42.These included neuropathological examination of material from experiments studying the attempted transmission of BSE to chickens and pigs (CVL 1991) and to mice (RVC 1994).
It was thought likely that at least some, and probably all, of the cases in zoo animals were caused by the BSE agent. Strong support for this hypothesis came from the findings of Bruce and others (1994) ( Bruce, M.E., Chree, A., McConnell, I., Foster, J., Pearson, G. & Fraser, H. (1994) Transmission of bovine spongiform encephalopathy and scrapie to mice: strain variation and species barrier. Philosophical Transactions of the Royal Society B 343, 405-411: J/PTRSL/343/405 ), who demonstrated that the pattern of variation in incubation period and lesion profile in six strains of mice inoculated with brain homogenates from an affected kudu and the nyala, was similar to that seen when this panel of mouse strains was inoculated with brain from cattle with BSE. The affected zoo bovids were all from herds that were exposed to feeds that were likely to have contained contaminated ruminant-derived protein and the zoo felids had been exposed, if only occasionally in some cases, to tissues from cattle unfit for human consumption.
10. The case of SE in a cheetah that occurred during the period, involved a 7 year-old female which had been born and lived all her life at Whipsnade (except for the final stages when she was moved to the Animal Hospital at Regent’s Park for diagnosis and treatment). This animal, which died in December 1993, had been fed on cuts of meat and bone from carcases of cattle unfit for human consumption and it was thought likely that she had been exposed to spinal cord (Kirkwood, J.K., Cunningham, A.A., Flach, E.J., Thornton, S.M. & Wells, G.A.H. (1995) Spongiform encephalopathy in another captive cheetah (Acinonyx jubatus): evidence for variation in susceptibility or incubation periods between species. Journal of Zoo and Wildlife Medicine 26, 577-582: J/ZWM/26/577).
11. During the period we also collated information on cases of SE that occurred in wild animals at or from other zoos in the British Isles. The total number of cases of which I was aware in June 1996, when I presented a review on occurrence of spongiform encephalopathies in zoo animals (at the Royal College of Pathologists’ Symposium on Transmitting prions: BSE, CJD, and other TSEs, The Royal Society, London, 4th July 1996), was 25, involving 10 species. The animals involved were all from the families Bovidae and Felidae, and comprised: 1 Nyala Tragelaphus angasi, 5 Eland Taurotragus oryx, 6 greater kudu Tragelaphus strepsiceros, 1 Gemsbok Oryx gazella, 1 Arabian oryx Oryx leucoryx, 1 Scimitar-horned oryx Oryx dammah, 4 Cheetah Acinonyx jubatus, 3 Puma Felis concolor 2 Ocelot Felis pardalis, and 1 Tiger Panthera tigris. (A spongiform encephalopathy, which was thought probably to have a different aetiology, had also been reported in 3 ostriches Struthio camelus in Germany). This list did not include cases of BSE in domesticated species in zoos (ie BSE in Ankole or other cattle, or SEs, assumed to be scrapie, in mouflon sheep Ovis musimon).
NEW URL ;
MONDAY, NOVEMBER 06, 2017
Experimental transfusion of variant CJD-infected blood reveals previously uncharacterised prion disorder in mice and macaque
''On secondary and tertiary transmissions, however, the proportion of PrPres positive animals gradually increased to almost 100%.
''Recent communications suggest that a similar situation might exist in other models of experimental exposure to prions involving swine32 and cattle33.''
''Experimental transfusion of variant CJD-infected blood reveals previously uncharacterised prion disorder in mice and macaque''
Holy Mad Cow Batman, i am thinking of that 10,000,000 POUNDS OF BLOOD LACED MEAT AND BONE MEAL IN COMMERCE WARNING LETTER back in 2007, see;
FRIDAY, NOVEMBER 3, 2017
BSE MAD COW TSE PRION DISEASE PET FOOD FEED IN COMMERCE INDUSTRY VS TERRY S. SINGELTARY Sr. A REVIEW
''I have a neighbor who is a dairy farmer. He tells me that he knows of several farmers who feed their cattle expired dog food. These farmers are unaware of any dangers posed to their cattle from the pet food contents. For these farmers, the pet food is just another source of protein.''
SATURDAY, NOVEMBER 4, 2017
FDA 589.2000, Section 21 C.F.R. Animal Proteins Prohibited in Ruminant Feed WARNING Letters and FEED MILL VIOLATIONS OBSERVATIONS 2017 to 2006
OFFICIAL REPORT U.K. GOVERNMENT DEFRA
Terry S. Singeltary Sr.