Published: 12 July 2021
Canine D163-PrP polymorphic variant does not provide complete protection against prion infection in small ruminant PrP context
Alba Marín-Moreno, Juan Carlos Espinosa, Patricia Aguilar-Calvo, Natalia Fernández-Borges, José Luis Pitarch, Lorenzo González & Juan María Torres Scientific Reports volume 11, Article number: 14309 (2021) Cite this article
1 Altmetric
Metricsdetails
Abstract
E/D163 polymorphism of dog prion protein (PrP) has been recently proposed as the variant responsible for canid prion resistance. To further investigate the protective role of this variant against prion replication, the transgenic mouse model OvPrP-Tg532 expressing sheep/goat PrP carrying the substitution D162 (equivalent to D163 position of dog PrP) was generated and intracranially inoculated with a broad collection of small ruminant prion strains. OvPrP-Tg532 mice showed resistance to classical bovine spongiform encephalopathy (BSE) from sheep and some classical scrapie isolates from sheep and goat but were susceptible to ovine atypical L-BSE and numerous classical scrapie isolates. Strikingly, some of these classical scrapie isolates showed a shift in their prion strain properties. These results suggest that other PrP residues apart from E/D163 variant of dog PrP or factors distinct than PrP may participate in prion resistance of canids and that different factors may be required for D162 sheep PrP to provide effective protection to sheep against ruminant prions.
snip...
Discussion
The dog-PrP D/E163 polymorphic variant has been recently proposed as responsible for the prion resistance of canids10,11. Such variant was found to protect against mouse-adapted strains RML, 22L and 301C in transgenic mice expressing the mouse D158 PrP variant equivalent to the dog D16310. Coexpression of both the wild-type and mutated PrPs in transgenic mice inoculated with mouse-adapted prion strains increased mice survival time12. Later, transgenic mice expressing dog PrP harboring the E163 polymorphic variant were resistant to classical and atypical L-BSE and classical and atypical scrapie prions11. Moreover, once the N163 mutation was introduced in transgenic mice expressing dog PrP, animals were susceptible to sheep classical BSE in vivo and to cattle and sheep classical BSE prions in vitro11. To further study the role exerted for this polymorphic variant in the susceptibility/resistance of prions, we generated the OvPrP-Tg532 mouse line. This line expresses physiological levels of small ruminant PrP harboring the mutation D162, analogue to the D/E163 polymorphic variant of dog PrP. These mice were intracranially inoculated with a broad panel of prion isolates with different strain features.
OvPrP-Tg532 proved to be resistant to classical BSE from ovine and caprine origin (Table 1) while its control counterpart model (OvPrP-Tg501) was susceptible with 100% attack rates. This result is in line with the previously published mouse model expressing the D158-mouse PrP, in which the BSE mouse-adapted strain 301C was unable to cause disease after intracerebral challenge10. However, dog PrP, which expresses in a natural manner the “resistant” D163 could eventually be misfolded in vitro by BSE and BSE-derived prions that retained their ability to infect bovine PrP transgenic mice16. Altogether, suggests the molecular compatibility between D163 dog PrP variant and classical BSE PrPSc at least in vitro. An in silico analysis of this acidic substitution revealed an electrostatic potential change on the surface of PrP when compared to its counterpart amino acid (asparagine). The acidic properties conferred by D/E residue disturb this region introducing a positively charged residue that might block the PrP conversion10.
However, when searching for “universal” PrP sequences that could drive resistance against prions it is important to bear in mind that susceptibility to TSEs depends on the PRNP genotype and the infectious strain17,18. Thus, a wide panel of prion isolates was inoculated in the above mentioned small ruminant transgenic mice to test the role of the singular D162 mutation. The two Italian scrapie isolates included in this study, which showed long incubation times in OvPrP-Tg501 (Table 1)15, were not able to infect D162 OvPrP-Tg532 mice. Two possible explanations could account for this fact. As these strains are classified as slow replicating prions, the PrP containing the D162 mutation may just elongate the survival times making the disease not able to appear within the mouse lifespan. A not fully protective effect but a significant delay in disease manifestation was also found in the highly prion susceptible bank vole PrP transgenic mouse model in which this substitution was introduced12. In this case, the substitution could trigger a protective effect by inducing protein alterations which attenuate the rate of fibril formation and the stability of newly formed fibrils10,19,20. Alternatively, a complete resistance against these Italian scrapie isolates could explain these results. In fact, in the mouse context, the D158 mouse model was also completely resistant to the mouse scrapie adapted strains RML and 22L10. With the aim of reducing incubation times of these slow replicating scrapie strains in the OvPrP-Tg532 model (that could interfere with a polymorphic barrier induced by the substitution D162), second passages will be necessary.
L-BSE and the non-Italian scrapie isolates tested in this panel were able to produce disease in the OvPrP-Tg532 mouse model with attack rates close to 100%. However, slightly longer incubation periods were found in almost all the cases when compared to OvPrP-Tg501 control model (Table 1). These results highlight the importance of using a wide diversity of prion isolates to test the role of a singular PrP mutation in the prion susceptibility/resistance. Therefore, the mutation D162 does not provide total resistance against prion infection in the small ruminant PrP context; it depends on the prion strain tested on each case. Although the successful first passage already shows that the D162 variant in sheep PrP does not provide complete resistance to these prion strains, the second passages would be very informative. Once fully adapted to replication in both D162 OvPrP-Tg532 and N162 OvPrP-Tg501 models, a proper comparison of the transmission properties among the two models could be done.
In addition, for sheep scrapie PS21 and goat scrapies F2, F10, S2 and S3 isolates, the molecular weight of the non-glycosylated PrP band changed from 21 to 19 kDa (Fig. 2). This shift in the strain characteristics was permanent even after transmission back into the OvPrP-Tg501 mice and solely caused by the D162 mutation.
There is no report of TSE infection in canids and the D/E163 polymorphic variant was pointed as responsible for this even in the mouse PrP context10,11. However, we prove that the phenomenon of susceptibility/resistance to prions is strongly strain-dependent and the reports in the mouse PrP context10,11 included other prion strains. In addition, the transmission barrier in the dog brain can be overcome using the PMCA technique for classical BSE prion agent16. These experiments were done using dog brain expressing the D163 PrP polymorphic variant, the same we introduced in the sheep PrP sequence. However, the transgenic mouse line that was found to be resistant to prion infection using a variety of strains, including cattle and sheep classical BSE, expressed the E163 PrP polymorphic variant11. Within the Canidae family, the D163 PrP variant is present in several species while the E163 PrP is restricted to domestic dogs. Thus suggesting that the D163 variant could pose some resistance to prion infection in a strain dependent manner, while the E163 variant may be a more robust protector. Although canids are resistant to TSEs in natural conditions, its PrP can be misfolded in vitro by the classical BSE agent16 whilst the present study points that its resistance cannot be fully attributed to this polymorphic allele since the introduction of the equivalent D162 mutation in sheep PrP did not confer absolute prion resistance. However, it must be taken into account that D162-sheep PrP is not analogue to the dog PrP sequence and therefore other factors may be required for D162-sheep PrP to provide effective protection to sheep against ruminant prions. In addition, other canid PrP residues, or even other genetic factors different than PrP may be involved in fully canid prion resistance. A multiple protein sequence alignment done for mouse, sheep and dog PrP reveals that few amino acid residues apart from D/E163 polymorphism in dog PrP are distinct between these three species (Fig. 4). Since D158 mice were found resistant to the three prion strains tested10,12, amino acid differences between dog and mouse PrP did not account for the prion resistance, at least for the strains tested there. However in the case of our OvPrP-Tg532 mice, 7 amino acid positions differ with the dog PrP sequence and these positions may also be responsible for canid resistance and/or for sheep susceptibility to prion infection (Fig. 4). Little is known from other genetic factors other than PrP affecting prion disease progression. Quantitative trait locus (QTL) mapping, the crossing of heterogeneous stock mice, expression profiling and human genome wide association studies (GWAS) have pointed to the existence of non-PrP genetic modifiers (reviewed in 21). The role that these genes and their coding proteins may pose in prion propagation is not known but they generally belong to neurodegeneration, immune response and protein folding and degradation pathways21. It has also been reported that susceptibility to prion strains is mainly governed by host PrPC while other host factors modulate strain features22.
With the reports existing up to now, the D162 mutation could have been considered interesting for the sheep and goat breeding selection programs conducted to reduce classical scrapie incidence within Europe. Although this polymorphism does not naturally exist in sheep and goats, genetically modified animals could have been produced. Unfortunately, our study demonstrates that D162 substitution does not provide total resistance against prion infection in the small ruminant PrP context, discarding this mutation as suitable for sheep and goat breeding selection programs.
3.3. Mr R J Higgins in conjunction with Mr G A Wells and Mr A C Scott would by the end of the year, identify the three brains that were from the ''POSITIVE'' end of the lesion spectrum.
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
HUGH MCDONAGH BSE CORRESPONDENCE SECTION
======================================
HOUND SURVEY
I am sorry, but I really could have been a co-signatory of Gerald's minute. I do NOT think that we can justify devoting any resources to this study, especially as larger and more important projects such as the pathogenesis study will be quite demanding. If there is a POLITICAL need to continue with the examination of hound brains then it should be passed entirely to the VI Service.
J W WILESMITH Epidemiology Unit 18 October 1991 Mr. R Bradley cc: Mr. G A H Wells
TSE & HOUNDS GAH WELLS (very important statement here...TSS)
HOUND STUDY 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. snip...
Norwegian dog may have died of mad cow disease
It has always been a puzzle why only FSE but not CSE [feline and canine spongiform encephalopathies] has been seen up to now. Dogs [more generally, zoo canids] were said to be a reassuring example of species barrier, so this is bad news, if it is confirmed. The question immediately arises of whether a large number of other CSE cases could have been missed. Britain has 7 million dogs and 7.7 million cats.
Nothing is known about either prion, no sequences published -- this is fast and cheap and should have been done years ago. The Norwegians will have a difficult time ruling out familial CSE because domestic dogs are likely to have a large number of polymorphisms fixed by inbreeding. The closest known sequences would be mink and ferret. -- webmaster
DATELINE: OSLO, April 20 Agence France Presse
An 11-year old dog in Norway that died recently may have been infected with " mad cow" disease, Norwegian television said quoting scientists who performed an autopsy on the animal. According to national television TV2, an autopsy at Norway's College of Veterinary Science showed changes in the dog's brain that resembled the changes in cattle and sheep afflicted with "mad cow" disease and scrapie, experts said.
"The dog was brought to us after it died. It had shown nervous symptoms for some time, and we were interested in performing an autopsy on it," pathology professor Jon Teige said. "The brain was examined and in connection with that, spongiform encephalopathy was found, changes in the brain that we judge to be very similar to those we see in scrapie and 'mad cow' disease," he added.
The institute has now sent the tests to another pathology laboratory in Oslo for confirmation. It has not yet been determined how the dog would have contracted the disease, though it is likely to date back to the late 1980s, when bone meal was used in dog food. According to Animal Health Board director Eivind Liven, it is "highly possible" that the infected food came from England.
Dagbladet, Aftenposten, Oslo, Norway. April 20-22, 1997
Norwegian scientists are now recognizing the possibility that the worlds first dog to suffer from probable Canine Spongiform Encephalopathy may have been genetically predisposed. It's definitely a possibility that this disease in dogs could be an inherited form, something similar to familial CJD in humans, says Bj¯rn Naess of the Norwegian Veterinary Institute. A final diagnosis is expected in a couple of weeks.
A Norwegian golden retriever may have died of Canine Spongiform Encephalopathy, possibly linked to BSE. Most pet food in Norway is imported, mainly from the UK, and before 1994 there was no quality-control inspection: "If the dog contracted the brain ailment, it probably was through dog food in the late 1980s", said Eivind Liven, Director of the National Animal Health Board.
The 11-year-old dog showed symptoms of psychiatric and neurological illness a couple of months ago, and died around Easter. An autopsy at Norway's Veterinary School showed changes in the brain consistent with those seen in the brains of cattle with late stage BSE.
Tissue samples from the brain of the dog will be studied by researchers at MAFF's Central Veterinary Laboratory, Weybridge, UK.
Norwegian Correspondent Report
Olav Hungnes
Natl.Inst.of Public Health, Dept.of Virology
P.O.Box 4404 Torshov, phone: (+47)22 04 25 20
N-0403 OSLO, NORWAY FAX: (+47)22 04 24 47
The story, first brought by Norwegian TV2, is that an 11 year old golden retriever was brought to the Norwegian College of Veterinary Medicine for an autopsy. The dog had shown neurological symptoms over a longer period. Microscopy of brain tissue showed spongiform encephalopathy. Samples have been sent to another pathological laboratory in Oslo (probably at Rikshospitalet (The National Hospital)), as well as to Weybridge Central Veterinary Institute, London, for further investigation. This is said to be the first reported case of spongiform encephalopathy in dogs.
Media focus has been on BSE-contaminated dog food as a possible cause. 95 % of dog food in this country is imported, and speculation goes that the dog could have got its disease from eating feed prepared from British meat-and-bone meal during the eighties. The possibility of genetic factors should, however, not be ignored. I would guess that investigation of the dog's PrP genotype is underway. Is anything known about polymorphism in dogs?
Source(in Norwegian): Articles from NTB, appearing in the newspaper Aftenposten Saturday and Tuesday
76 pages on hound study;
snip...
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.
snip...
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).
*** DEFRA TO SINGELTARY ON HOUND STUDY AND BSE 2001 ***
DEFRA Department for Environment, Food & Rural Affairs Area 307, London, SW1P 4PQ Telephone: 0207 904 6000 Direct line: 0207 904 6287 E-mail: h.mcdonagh.defra.gsi.gov.uk
GTN: FAX: Mr T S Singeltary P.O. Box Bacliff Texas USA 77518 21 November 2001
Dear Mr Singeltary
TSE IN HOUNDS Thank you for e-mail regarding the hounds survey. I am sorry for the long delay in responding. As you note, the hound survey remains unpublished. However the Spongiform Encephalopathy Advisory Committee (SEAC), the UK Government's independent Advisory Committee on all aspects related to BSE-like disease, gave the hound study detailed consideration at their meeting in January 1994. As a summary of this meeting published in the BSE inquiry noted, the Committee were clearly concerned about the work that had been carried out, concluding that there had clearly been problems with it, particularly the control on the histology, and that it was more or less inconclusive. However was agreed that there should be a re-evaluation of the pathological material in the study.
Later, at their meeting in June 95, The Committee re-evaluated the hound study to see if any useful results could be gained from it. The Chairman concluded that there were varying opinions within the Committee on further work. It did not suggest any further transmission studies and thought that the lack of clinical data was a major weakness.
Overall, it is clear that SEAC had major concerns about the survey as conducted. As a result it is likely that the authors felt that it would not stand up to peer review and hence it was never published. As noted above, and in the detailed minutes of the SEAC meeting in June 95, SEAC considered whether additional work should be performed to examine dogs for evidence of TSE infection. Although the Committee had mixed views about the merits of conducting further work, the Chairman noted that when the Southwood Committee made their recommendation to complete an assessment of possible spongiform disease in dogs, no TSEs had been identified in other species and hence dogs were perceived as a high risk population and worthy of study. However subsequent to the original recommendation, made in 1990, a number of other species had been identified with TSE ( e.g. cats) so a study in hounds was less critical.
For more details see-
new url;
PRION 2016 TOKYO http://prion2016.org/
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).
References
http://caninespongiformencephalopathy.blogspot.com/2012/03/canine-spongiform-encephalopathy-new.html
=======================================
2013 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.
Abstract
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
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
Friday, March 8, 2013
Dogs may have been used to make Petfood and animal feed
http://web.archive.org/web/20090505233052/http://www.bseinquiry.gov.uk/files/yb/1989/05/03007001.pdf
http://web.archive.org/web/20090505233041/http://www.bseinquiry.gov.uk/files/yb/1989/05/16001001.pdf
http://web.archive.org/web/20090506015917/http://www.bseinquiry.gov.uk/files/yb/1989/05/16002001.pdf
Natural case of Spongiform Encephalopathy in a Cat
http://web.archive.org/web/20090506015733/http://www.bseinquiry.gov.uk/files/yb/1990/05/09002001.pdf
http://web.archive.org/web/20090506041332/http://www.bseinquiry.gov.uk/files/yb/1990/05/10005001.pdf
Spongiform Encephalopathy in a captive Puma
http://web.archive.org/web/20090506032628/http://www.bseinquiry.gov.uk/files/yb/1992/11/13001001.pdf
Deer Brain Survey
http://web.archive.org/web/20090506025229/http://www.bseinquiry.gov.uk/files/yb/1991/11/20004001.pdf
http://web.archive.org/web/20090506032702/http://www.bseinquiry.gov.uk/files/yb/1992/11/04002001.pdf
——– Original Message ——–
Subject: Cognitive Dysfunction Syndrome (CDS) or MAD DOG DISEASE
Date: Mon, 4 Apr 2005 13:14:12 -0500
From: “Terry S. Singeltary Sr.”
Reply-To: Bovine Spongiform Encephalopathy To: BSE-L@KALIV.UNI-KARLSRUHE.DE
##################### Bovine Spongiform Encephalopathy #####################
Greetings,
THIS is a hoot from purina, as to why your dog might be acting a bit strangely. nothing mentioned about the decades of feeding those dogs the same thing we been feeding humans, potentially tainted feed, tainted with TSEs. dog food (like cat food) is loaded with SRMs. new regulations are suppose to go into effect, but that will not help all the animals exposed over the decades. some data on dogs, cats and TSE. THE reason of bringing this up again, there was a small write-UP in question to a Dr. Michael Fox about this in the Houston Chronicle ‘Easing Life of older dogs’ ; ‘My black Lab is 12 years old and has entered his ”Alzheimer’s” phase … ‘it’s called canine cognitive dysfunction disorder …
snip…
end SO, went to see what the feed sellers say about this ; Does your dog suffer from Cognitive Dysfunction Syndrome? Find out how to cope with dog dementia. Typically, an elderly dog tends to sleep longer hours and slow down in comparison to his or her younger or middle-aged years. But some older dogs exhibit behaviour changes that appear abnormal. Until recently, such changes had been attributed to normal aging, for which little could be done. However, behaviour changes in elderly dogs may be due to a disorder called Cognitive Dysfunction Syndrome. Cognitive Dysfunction Syndrome (CDS) is associated with a number of clinical signs. The diagnosis is made when dogs exhibit multiple signs which develop in old age, and which are not completely due to other medical or physical problems. Dogs with CDS may appear disoriented in familiar surroundings such as their own homes, wandering aimlessly and perhaps appearing to ‘forget’ to back out of corners. Those that were flawlessly housetrained throughout their lives may start to have ‘accidents’. They may no longer greet their owners at the door, bring them balls to throw, or appear to care about being petted. And while they may sleep throughout the day, the night may bring restlessness and increased wandering, as though their biological clocks were reversed. Because aging dogs are increasingly susceptible to medical problems (see ‘The Elderly Dog’), regular examinations by a vet are important. Only a veterinary surgeon can determine whether your dog’s behaviour changes are due to CDS (rather than, for example, liver, heart, or kidney disease). If a diagnosis of CDS is made, your vet may recommend treatment. Behaviour changes in aging dogs may be responsive to treatment. Whatever, happens, after a lifetime of unconditional love and companionship, our older dogs deserve every consideration we can give them.
Is your dog elderly? If so, you’ll have to ease their way. Here’s how… Often dogs are older than we think they are. It’s hard to guess-timate how old a dog is as there are considerable breed differences between dogs. Generally speaking, small dogs live the longest (a Yorkshire Terrier is considered ‘old’ at 10 years), while large breeds have relatively short lifespans (a Great Dane is considered ‘old’ at six years). Here we help you tell if your dog is old and then advise you on how to make your elderly dog’s life easier& The physical signs: Physical inactivity- Difficulty getting up after lying down for a while or after a long walk can be a sign of deteriorating joints due to wear and tear through life. Some dogs may be less keen to go for walks and prefer to curl up in a warm bed. Others may be initially keen to go out but as the joints ease with gentle exercise may be tempted to do a little too much with dire consequences later in the day as joints stiffen up and become even worse. Hair loss- The skin may appear dry and scaly while the coat texture may be harsher, thinner with bald patches or white hairs. Often the coat is dull and the colour may be less vivid. Dog breath- Bad teeth or gum infections may cause bad breath or inability to eat. A common sign is of food being dropped or excessive salivation and pawing at the mouth. Swellings appearing below the eye may be signs of tooth root abscesses and need veterinary attention. Lumps and bumps- Warts, fatty lumps and even tumours may appear in old age. Check these out with your vet as early detection may save your dog’s life. Loss of bladder control- Incontinence: this is sometimes associated with changes in thirst but sometimes it’s associated with sore joints, which make posturing difficult. Mental alertness- Many older dogs become confused and fail to recognise their surroundings, their name or their owner! They may become less interested in food or what is happening around them. Some dogs appear dull and depressed while others become disobedient or destructive. Many older dogs get anxious if left alone for any length of time. Sleep- Many older dogs sleep more during the day but sleep less at night. Some may prowl around the house at night because of sore joints, senility or even loneliness. Ways to make your dog’s life easier If your dog shows these signs, consider the following to make your dog’s life easier: * Install ramps to allow your dog to get back into the house from the garden. * Dry your dog well if you’ve been walking in the rain. * Arthritic dogs may have trouble standing up after lying down for a period of time so gently rub the muscles to warm them up and relieve some of the stiffness. * Understand that changes in oxygen flow to the brain in old age mean dogs are likely to remember events from the past much better than if they happened yesterday. They get confused. Another change experienced by some dogs, cognitive dysfunction syndrome, may affect behaviour in more general ways, similar to the changes caused by senile dementia in humans. * Some retraining may be necessary. Often using treats is a particularly good way to retrain the older dog. Food is a great motivator but beware of obesity in a less active older dog. * Perhaps amounts at mealtimes need adjusting as elderly dogs usually become less active and require fewer calories. But conversely in some dogs, particularly the very old, more calories are needed. The main thing is to keep an eye on the dog’s weight, however. * Deteriorating vision and hearing may reduce a dog’s ability to respond to his environment. He/she may not greet you immediately only because he/she isn’t aware that you’ve arrived. Take a look at how to cope with blindness and deafness. * Older dogs may also develop a fear of thunderstorms. The booming sounds of thunder may be exaggerated because of a loss of high-frequency hearing. * Ensure their bed is in a warm draught-free place to make sleep time that bit more comfortable.
Subject: Canine spongiform encephalopathy?
From: J Ralph Blanchfield
Reply-To: Bovine Spongiform Encephalopathy
Date: Tue, 29 Apr 1997 06:51:38 GMT
Content-Type: text/plain
Parts/Attachments: text/plain (83 lines)
Reply
Hello Everyone,
Report in Daily Telegraph, 29 April.
Tests on labrador could prove BSE has spread to dogs
By Roger Highfield, Science Editor
BRAIN sections from a dog have been sent to Britain by Norwegian pathologists to confirm that it is the first example of canine spongiform disease, akin to BSE.
The move came as Labour accused the Government of excessive secrecy for not publishing results of a 1991 study to investigate the possibility of BSE being transferred to dogs.
The 11-year-old labrador suffered nervous symptoms, lack of muscle co-ordination and seizures. A post mortem examination showed that its brain had a spongiform appearance, said Prof Jon Teige, a pathologist at the Norwegian College of Veterinary Medicine in Oslo.
“To our surprise, we saw these lesions in the brain similar to those observed in scrapie in sheep and mad cow disease,” said Prof Teige. If confirmed, it would mark the first example of the disease in a dog.
Samples have had been sent to the Institute of Animal Health’s neuropathogenesis unit in Edinburgh for a second opinion. “Although there are some features of the pathology in common with spongiform encephalopathies, a number of other conditions have similar aspects,” said Dr Chris Bostock, of the institute.
If confirmed, it is also important to determine if it is the spontaneous form of BSE or if the dog had been infected in its diet and had a transmissible disease. About 95 per cent of Norway’s dog and cat food is imported, mainly from Britain. Parts of bovine material, which could contain BSE, were removed from the animal food chain in 1990.
Scientists are interested in whether dogs are susceptible but confirmation would not change the big picture of BSE, Dr Bostock said. Dr Gavin Strang, shadow food minister, yesterday accused Douglas Hogg, the Agriculture Minister, of secrecy over BSE research. “This work on possible BSE in dogs was funded by the public,” he said. “Results should have been made public.”
The Government ruled out further research on dogs yesterday despite disclosures in a report six years ago that there was a possibility that they could catch a form of mad cow disease from contaminated food. “It is unnecessary,” said a spokesman. “There is no threat to human or animal health.”
Tests six years ago by ministry experts on the brains of 444 hunting hounds found some abnormalities called fibrils. However, some brains had started to degenerate, making the results ambiguous.
The results were passed to the Spongiform Encephalopathy Advisory Committee, which agreed that they were inconclusive and ruled out further research because there was no public health issue. “We don’t eat dogs in Britain,” the spokesman said.
Mr Hogg said that the research on dogs and BSE “adds nothing to human knowledge” during a tour of the North-East which included a visit to a sausage factory in marginal Stockton South.
End of Telegraph Report.
Regards
Ralph
******************************************************************
J Ralph Blanchfield Food Science, Food Technology & Food Law Consultant Chair, IFST External Affairs Web Editor, Institute of Food Science & Technology IFST Web address:
******************************************************************>
Subject: Re: Canine spongiform encephalopathy?
From: “Hans G. Andersson”
Reply-To: Bovine Spongiform Encephalopathy
Date: Tue, 29 Apr 1997 06:02:33 -0700
Content-Type: text/plain
Parts/Attachments: text/plain (38 lines)
Reply
Hello Ralph and everybody,
Excerpt from the article you forwarded:
“The Government ruled out further research on dogs yesterday despite disclosures in a report six years ago that there was a possibility that they could catch a form of mad cow disease from contaminated food. “It is unnecessary,” said a spokesman. “There is no threat to human or animal health.”
Tests six years ago by ministry experts on the brains of 444 hunting hounds found some abnormalities called fibrils. However, some brains had started to degenerate, making the results ambiguous.
The results were passed to the Spongiform Encephalopathy Advisory Committee, which agreed that they were inconclusive and ruled out further research because there was no public health issue. “We don’t eat dogs in Britain,” the spokesman said.
Mr Hogg said that the research on dogs and BSE “adds nothing to human knowledge” during a tour of the North-East which included a visit to a sausage factory in marginal Stockton South.”
I got two dogs myself, both 13 years old and fed British pet food during the period 1984-89.
The statement from the British government is tasteless!
Best regards,
Hans
Hans G. Andersson, NYC — hasse@sprynet.com Editor, Ebola section of OUTBREAK http://www.outbreak.org/ ;
“There is a crack in everything. That’s how the light gets in.” Leonard Cohen
Subject: Re: Canine Spongiform Encephalopathy?
From: Olav Hungnes
Reply-To: Bovine Spongiform Encephalopathy
Date: Wed, 23 Apr 1997 10:19:14 +0200
Content-Type: text/plain
Parts/Attachments: text/plain (47 lines)
Reply
Date: Mon, 21 Apr 1997 20:59:16 +0200 From: Torsten Brinch Subject: Canine Spongiform Encephalopathy?
Hello everyone,
I wondered if we have a Norwegian subscriber, who could brief the list on the suspected case of spongiform encephalopathy in a Norwegian dog?
Best regards,
Torsten Brinch
Torsten Brinch – Risboege, 6640, Denmark – e-mail: iaotb@inet.uni-c.dk http://inet.uni-c.dk/~iaotb/ IAO Agrochemical Pages Denmark
The story, first brought by Norwegian TV2, is that an 11 year old golden retriever was brought to the Norwegian College of Veterinary Medicine for an autopsy. The dog had shown neurological symptoms over a longer period. Microscopy of brain tissue showed spongiform encephalopathy.
Samples have been sent to another pathological laboratory in Oslo (probably at Rikshospitalet (The National Hospital)), as well as to Weybridge Central Veterinary Institute, London, for further investigation.
This is said to be the first reported case of spongiform encephalopathy in dogs.
Media focus has been on BSE-contaminated dog food as a possible cause. 95 % of dog food in this country is imported, and speculation goes that the dog could have got its disease from eating feed prepared from British meat-and-bone meal during the eighties. The possibility of genetic factors should, however, not be ignored. I would guess that investigation of the dog’s PrP genotype is underway. Is anything known about polymorphism in dogs?
Source(in Norwegian, for the benefit of Torsten): Articles from NTB, appearing in the newspaper Aftenposten Saturday and Tuesday , — __________________________________________________________________________
Olav Hungnes olavhung@idgonline.no Natl.Inst.of Public Health, Dept.of Virology ohungnes@embnet.uio.no P.O.Box 4404 Torshov, phone: (+47)22 04 25 20 N-0403 OSLO, NORWAY FAX: (+47)22 04 24 47 http://home.idgonline.no/~ohungnes/>> ;
Subject: Re: Canine Spongiform Encephalopathy
From: “Hans G. Andersson”
Reply-To: Bovine Spongiform Encephalopathy
Date: Tue, 22 Apr 1997 00:15:18 -0700
Content-Type: text/plain
Parts/Attachments: text/plain (41 lines)
Reply
Hi Torsten and everybody,
Here’s some additional information from media in Norway:
A Norwegian golden retriever may have died of Canine Spongiform Encephalopathy, possibly linked to BSE.
Most pet food in Norway is imported, mainly from the UK, and before 1994 there was no quality-control inspection:
“If the dog contracted the brain ailment, it probably was through dog food in the late 1980s”, said Eivind Liven, Director of the National Animal Health Board.
The 11-year-old dog showed symptoms of psychiatric and neurological illness a couple of months ago, and died around Easter. An autopsy at Norway’s Veterinary School showed changes in the brain consistent with those seen in the brains of cattle with late stage BSE.
Tissue samples from the brain of the dog will be studied by researchers at MAFF’s Central Veterinary Laboratory, Weybridge, UK.
Source: Dagbladet in Oslo, Norway. April 20 and 21, 1997
Best regards,
Hans
Hans G. Andersson, NYC — hasse@sprynet.com Editor, Ebola section of OUTBREAK http://www.outbreak.org/
“There is a crack in everything. That’s how the light gets in.” Leonard Cohen
Spongiform polioencaphalopathy in a dog
Cooke MM, Johnstone AC, Wells GAH
Surveillance, Volume 24, Issue 2, p 21, Jan 1997
View full text (390 KB) | Abstract/Full Details | Export citation
More
Article class: Case Study
Subject Terms: Idiopathic disease, Nervous system/neurology
Animal Type: Companion animal, Dog
Publisher: Ministry for Primary Industries
Scrapie and bovine spongiform encephalopathy are the most publicized of the prion-induced diseases of animals, but transmissible disease of this type have been described in other species, namely mink, cats and cervids. It is possible that similar but hitherto unrecognized spongiform encephalopathies also occur in other domestic and wild animal species. the following report of a recent investigation into an undiagnosed canine central nervous system disorder with histopathological brain lesions of spongiosis illustrates the vigilance with which MAF Quality Management veterinary pathologist investigate the disease status of New Zealand's livestock.
A 3-year-old female pedigree Shetland sheepdog with a 12 to 18 month history of progressive neurological signs, including ataxia, loss of long vision, hearing impairment and aggression, was examined at a veterinary clinic in the central North Island. The owners reported that the dog developed incoordination at about 1 year of age, and this progressed from clumsiness to a highstepping gait, poor placing and sideways collapse of the hind legs. There was no history of seizures or paresis. Serum biochemical and haematological examinations in December 1995 were unremarkable. The clinician examined the dog again in March 1996, and tentatively diagnosed a neuronal storage disease. Because of the progressive and intractable nature of the condition, the owners elected euthanasia and agreed that the brain could be removed for histopathological examination.
Sections of the fixed brain showed vacuolation of grey matter neuropil, including neuronal perikarya (Figure 1) which occasionally also contained coarse granules. The lesions were generally bilaterally symmetrical and involved the vestibular, medial and lateral geniculate nuclei, central grey matter of the midbrain, oculomotor nucleus and thalamic nuclei. The lesions were most striking in the thalamic nuclei. There was also evidence of a mild nonsuppurative meningitis and mild spongiosis of white matter tracts in some parts of the cerebrum.
The application of stains to demonstrate intraneuronal storage material ruled out a neuronal storage disease. Although there was no evidence of astrocytosis, microgliosis or amyloid plaques, transmissible spongiform encephalopathy (TSE) was included in the differential diagnosis on the basis of the history of a progressive neuropathy, and the nature, location and extent of the lesions. A second opinion was sought from Dr GAH Wells from the Central Veterinary Laboratory in UK, who considered the clinical history and histopathology, including negative results of immunohistochemical staining using 3F4 antibody to detect PrP protein, and decided that the disease was unlikely to be have been prion-induced. However, definitive exclusion of a TSE would require other methods to detect and transmit PrP. Both the demonstration and transmission of PrP require fresh tissues, which were not available in this case. TSEs have been transmitted from formalin fixed tissue, but fresh tissue is preferable.
The dog was born in New Zealand in 1993 but her parents were imported from Australia, the mother in 1990 and the father in 1992. Breeding records showed several lines of common ancestry and inbreeding, the closest relationship being that the dog’s grandmother was also her mother. The mother had produced two previous litters without problems, and the father’s two sisters in New Zealand were also normal. The diet comprised commercial and household sources of food with no access to meat-based products from the UK.
While the diagnosis of a TSE remains unlikely, it cannot be ruled out absolutely. The most likely diagnosis is a metabolic or genetic disorder, with the record of inbreeding favouring the latter.
MM Cook and AC Johnstone
MAF Quality Management
Palmerston North Animal Health Laboratory
Email: cookem@pnorth.mqm.govt.nz
GAH Wells
Central Veterinary Laboratory
New Haw. Addlestone,
Surrey KT15 3NB
United Kingdom
GREETINGS AGAIN,
IT SEEMS THE USDA ET AL have taken a page, or two, from the U.K. et al on screwing up brains for the testing of Transmissible Spongiform Encephalopathy BSE i.e. mad cow disease (all strains), when they do not want to document it.
From: TSS Subject: USDA OIG SEMIANNUAL REPORT TO CONGRESS FY 2007 1st Half (bogus BSE sampling FROM HEALTHY USDA CATTLE) Date: June 21, 2007 at 2:49 pm PST...snip...end...tss
***moving on, I am beginning to question this Red Deer Ataxia, kind of reminds me of the infamous hound ataxia and the hound study for BSE. but that’s another very long drawn out debacle. I can share some links below for those that might still be interested in this old stuff, but they are questioning now the mad dog disease i.e. or what I call CSE canine spongiform encephalopathy...
Red Deer Ataxia or Chronic Wasting Disease CWD TSE PRION?
could this have been cwd in the UK back in 1970’S ???
Veterinary Pathology Onlinevet.sagepub.com Published online before print February 27, 2014, doi: 10.1177/0300985814524798 Veterinary Pathology February 27, 2014 0300985814524798
Lesion Profiling and Subcellular Prion Localization of Cervid Chronic Wasting Disease in Domestic Cats
D. M. Seelig1⇑ A. V. Nalls1 M. Flasik2 V. Frank1 S. Eaton2 C. K. Mathiason1 E. A. Hoover1 1Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, CO, USA 2Department of Biomedical Sciences, Colorado State University, Fort Collins, CO, USA D. M. Seelig, University of Minnesota, Department of Veterinary Clinical Sciences, Room 339 VetMedCtrS, 6192A (Campus Delivery Code), 1352 Boyd Ave, St Paul, MN 55108, USA. Email address: dseelig@umn.edu
Abstract
Chronic wasting disease (CWD) is an efficiently transmitted, fatal, and progressive prion disease of cervids with an as yet to be fully clarified host range. While outbred domestic cats (Felis catus) have recently been shown to be susceptible to experimental CWD infection, the neuropathologic features of the infection are lacking. Such information is vital to provide diagnostic power in the event of natural interspecies transmission and insights into host and strain interactions in interspecies prion infection. Using light microscopy and immunohistochemistry, we detail the topographic pattern of neural spongiosis (the “lesion profile”) and the distribution of misfolded prion protein in the primary and secondary passage of feline CWD (FelCWD). We also evaluated cellular and subcellular associations between misfolded prion protein (PrPD) and central nervous system neurons and glial cell populations. From these studies, we (1) describe the novel neuropathologic profile of FelCWD, which is distinct from either cervid CWD or feline spongiform encephalopathy (FSE), and (2) provide evidence of serial passage-associated interspecies prion adaptation. In addition, we demonstrate through confocal analysis the successful co-localization of PrPD with neurons, astrocytes, microglia, lysosomes, and synaptophysin, which, in part, implicates each of these in the neuropathology of FelCWD. In conclusion, this work illustrates the simultaneous role of both host and strain in the development of a unique FelCWD neuropathologic profile and that such a profile can be used to discriminate between FelCWD and FSE.
prion chronic wasting disease immunohistochemistry interspecies cat feline spongiform encephalopathy transmissible spongiform encephalopathy adaptation species barrier
Monday, August 8, 2011 Susceptibility of Domestic Cats to CWD Infection
Oral.29: Susceptibility of Domestic Cats to CWD Infection
Amy Nalls, Nicholas J. Haley, Jeanette Hayes-Klug, Kelly Anderson, Davis M. Seelig, Dan S. Bucy, Susan L. Kraft, Edward A. Hoover and Candace K. Mathiason†
Colorado State University; Fort Collins, CO USA†Presenting author; Email: ckm@lamar.colostate.edu
Domestic and non-domestic cats have been shown to be susceptible to one prion disease, feline spongiform encephalopathy (FSE), thought to be transmitted through consumption of bovine spongiform encephalopathy (BSE) contaminated meat. Because domestic and free ranging felids scavenge cervid carcasses, including those in CWD affected areas, we evaluated the susceptibility of domestic cats to CWD infection experimentally. Groups of n = 5 cats each were inoculated either intracerebrally (IC) or orally (PO) with CWD deer brain homogenate. Between 40–43 months following IC inoculation, two cats developed mild but progressive symptoms including weight loss, anorexia, polydipsia, patterned motor behaviors and ataxia—ultimately mandating euthanasia. Magnetic resonance imaging (MRI) on the brain of one of these animals (vs. two age-matched controls) performed just before euthanasia revealed increased ventricular system volume, more prominent sulci, and T2 hyperintensity deep in the white matter of the frontal hemisphere and in cortical grey distributed through the brain, likely representing inflammation or gliosis. PrPRES and widely distributed peri-neuronal vacuoles were demonstrated in the brains of both animals by immunodetection assays. No clinical signs of TSE have been detected in the remaining primary passage cats after 80 months pi. Feline-adapted CWD was sub-passaged into groups (n=4 or 5) of cats by IC, PO, and IP/SQ routes. Currently, at 22 months pi, all five IC inoculated cats are demonstrating abnormal behavior including increasing aggressiveness, pacing, and hyper responsiveness.
*** Two of these cats have developed rear limb ataxia. Although the limited data from this ongoing study must be considered preliminary, they raise the potential for cervid-to-feline transmission in nature.
AD.63:
Susceptibility of domestic cats to chronic wasting disease
Amy V.Nalls,1 Candace Mathiason,1 Davis Seelig,2 Susan Kraft,1 Kevin Carnes,1 Kelly Anderson,1 Jeanette Hayes-Klug1 and Edward A. Hoover1 1Colorado State University; Fort Collins, CO USA; 2University of Minnesota; Saint Paul, MN USA
Domestic and nondomestic cats have been shown to be susceptible to feline spongiform encephalopathy (FSE), almost certainly caused by consumption of bovine spongiform encephalopathy (BSE)-contaminated meat. Because domestic and free-ranging nondomestic felids scavenge cervid carcasses, including those in areas affected by chronic wasting disease (CWD), we evaluated the susceptibility of the domestic cat (Felis catus) to CWD infection experimentally. Cohorts of 5 cats each were inoculated either intracerebrally (IC) or orally (PO) with CWD-infected deer brain. At 40 and 42 mo post-inoculation, two IC-inoculated cats developed signs consistent with prion disease, including a stilted gait, weight loss, anorexia, polydipsia, patterned motor behaviors, head and tail tremors, and ataxia, and progressed to terminal disease within 5 mo. Brains from these two cats were pooled and inoculated into cohorts of cats by IC, PO, and intraperitoneal and subcutaneous (IP/SC) routes. Upon subpassage, feline-adapted CWD (FelCWD) was transmitted to all IC-inoculated cats with a decreased incubation period of 23 to 27 mo. FelCWD was detected in the brains of all the symptomatic cats by western blotting and immunohistochemistry and abnormalities were seen in magnetic resonance imaging, including multifocal T2 fluid attenuated inversion recovery (FLAIR) signal hyper-intensities, ventricular size increases, prominent sulci, and white matter tract cavitation. Currently, 3 of 4 IP/SQ and 2 of 4 PO inoculared cats have developed abnormal behavior patterns consistent with the early stage of feline CWD.
*** These results demonstrate that CWD can be transmitted and adapted to the domestic cat, thus raising the issue of potential cervid-to- feline transmission in nature.
PO-081: Chronic wasting disease in the cat— Similarities to feline spongiform encephalopathy (FSE)
FELINE SPONGIFORM ENCEPHALOPATHY FSE
Spongiform Encephalopathy In Pigs
MF580391/1 0187
TO Dr J Metters IPCS FROM DO Hagger MCA/B
DATE 21 September 1990
cc Dr Jones (OR)
Dr Jefferys (OR}
Dr Rotblat (OR)
Dr Raine
Dr Purves
Dr Pickles
Dr Richardson HDD
SPONGTFORM ENCEPHALOPATHY IN PIGS
1. With reference to Dr Pickles’ minute to Dr Richardson and me of 20 September, I formally acknowledge that attention has been drawn to paragraph 7 of the internal minutes of the Tyrrell committee following its meeting on 19 September. The MCA are preparing papers for the next meeting of the CSM's Working Group which is scheduled for 31 October.
2. The questionnaires issued in 1989 by the MCA following Southwood sought information from the manufacturers of medicinal products on the use of tissue from all animal species, not just of bovine. Our records show that while some use is made of porcine materials in medicinal products, the only products which would appear to be in a hypothetically “higher risk" area are the adrenocorticotrophic hormone for which the source material comes from outside the United Kingdom, namely America China Sweden France and Germany. The products are manufactured by Ferring and Armour. A further product, "Zenoderm Corium implant" manufactured by Ethicon, an) makes use of porcine skin - which is not considered to be a “high See risk" tissue, - but one of its uses is described in the data sheet as ''in dural replacement' This product is sourced: from the” United Kingdom. Papers on both these products are being prepared by the MCA for consideration by the CSM Working Party at its next meeting.
LINE TO TAKE
3. If questions on pharmaceuticals are raised at the Press conference, the suggested line to take is as follows:-
"There are no medicinal products licensed for use on the market which make use of UK-derived porcine tissues with which any hypothetical “high risk" ‘might be associated. The results of the recent experimental work at the CSM will be carefully examined by the CSM‘s Working Group on spongiform encephalopathy at its next meeting.
DO Hagger RM 1533 MT Ext 3201
2021 Transmissible Spongiform Encephalopathy TSE Prion End of Year Report 2020
CJD FOUNDATION VIRTUAL CONFERENCE CJD Foundation Research Grant Recipient Reports Panel 2 Nov 3, 2020
zoonotic potential of PMCA-adapted CWD PrP 96SS inoculum
4 different CWD strains, and these 4 strains have different potential to induce any folding of the human prion protein.
***> PIGS, WILD BOAR, CWD <***
***> POPULATIONS OF WILD BOARS IN THE UNITED STATES INCREASING SUPSTANTUALLY AND IN MANY AREAS WE CAN SEE A HIGH DENSITY OF WILD BOARS AND HIGH INCIDENT OF CHRONIC WASTING DISEASE
HYPOTHOSIS AND SPECIFIC AIMS
HYPOTHOSIS
BSE, SCRAPIE, AND CWD, EXPOSED DOMESTIC PIGS ACCUMULATE DIFFERENT QUANTITIES AND STRAINS OF PRIONS IN PERIPHERAL TISSUES, EACH ONE OF THEM WITH PARTICULAR ZOONOTIC POTENTIALS
Final Report – CJD Foundation Grant Program A.
Project Title: Systematic evaluation of the zoonotic potential of different CWD isolates. Principal Investigator: Rodrigo Morales, PhD.
Systematic evaluation of the zoonotic potential of different CWD isolates. Rodrigo Morales, PhD Assistant Professor Protein Misfolding Disorders lab Mitchell Center for Alzheimer’s disease and Related Brain Disorders Department of Neurology University of Texas Health Science Center at Houston Washington DC. July 14th, 2018
Conclusions and Future Directions • We have developed a highly sensitive and specific CWD-PMCA platform to be used as a diagnostic tool. • Current PMCA set up allow us to mimic relevant prion inter-species transmission events. • Polymorphic changes at position 96 of the prion protein apparently alter strain properties and, consequently, the zoonotic potential of CWD isolates. • Inter-species and inter-polymorphic PrPC → PrPSc conversions further increase the spectrum of CWD isolates possibly present in nature. • CWD prions generated in 96SS PrPC substrate apparently have greater inter-species transmission potentials. • Future experiments will explore the zoonotic potential of CWD prions along different adaptation scenarios, including inter-species and inter-polymorphic.
Research Project: TRANSMISSION, DIFFERENTIATION, AND PATHOBIOLOGY OF TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES Location: Virus and Prion Research
Title: Disease-associated prion protein detected in lymphoid tissues from pigs challenged with the agent of chronic wasting disease
Author item MOORE, SARAH - Orise Fellow item Kunkle, Robert item KONDRU, NAVEEN - Iowa State University item MANNE, SIREESHA - Iowa State University item SMITH, JODI - Iowa State University item KANTHASAMY, ANUMANTHA - Iowa State University item WEST GREENLEE, M - Iowa State University item Greenlee, Justin 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: Chronic wasting disease (CWD) is a naturally-occurring, fatal neurodegenerative disease of cervids. We previously demonstrated that disease-associated prion protein (PrPSc) can be detected in the brain and retina from pigs challenged intracranially or orally with the CWD agent. In that study, neurological signs consistent with prion disease were observed only in one pig: an intracranially challenged pig that was euthanized at 64 months post-challenge. The purpose of this study was to use an antigen-capture immunoassay (EIA) and real-time quaking-induced conversion (QuIC) to determine whether PrPSc is present in lymphoid tissues from pigs challenged with the CWD agent.
Methods: At two months of age, crossbred pigs were challenged by the intracranial route (n=20), oral route (n=19), or were left unchallenged (n=9). At approximately 6 months of age, the time at which commercial pigs reach market weight, half of the pigs in each group were culled (<6 month challenge groups). The remaining pigs (>6 month challenge groups) were allowed to incubate for up to 73 months post challenge (mpc). The retropharyngeal lymph node (RPLN) was screened for the presence of PrPSc by EIA and immunohistochemistry (IHC). The RPLN, palatine tonsil, and mesenteric lymph node (MLN) from 6-7 pigs per challenge group were also tested using EIA and QuIC.
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 month group was positive by EIA. PrPSc was detected by QuIC in at least one of the lymphoid tissues examined in 5/6 pigs in the intracranial <6 months group, 6/7 intracranial >6 months group, 5/6 pigs in the oral <6 months group, and 4/6 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.
Research Project: Pathobiology, Genetics, and Detection of Transmissible Spongiform Encephalopathies Location: Virus and Prion Research
Title: The agent of chronic wasting disease from pigs is infectious in transgenic mice expressing human PRNP
Author item MOORE, S - Orise Fellow item Kokemuller, Robyn item WEST-GREENLEE, M - Iowa State University item BALKEMA-BUSCHMANN, ANNE - Friedrich-Loeffler-institut item GROSCHUP, MARTIN - Friedrich-Loeffler-institut item Greenlee, Justin Submitted to: Prion Publication Type: Abstract Only Publication Acceptance Date: 5/10/2018 Publication Date: 5/22/2018 Citation: Moore, S.J., Kokemuller, R.D., West-Greenlee, M.H., Balkema-Buschmann, A., Groschup, M.H., Greenlee, J.J. 2018. The agent of chronic wasting disease from pigs is infectious in transgenic mice expressing human PRNP. Prion 2018, Santiago de Compostela, Spain, May 22-25, 2018. Paper No. WA15, page 44.
Interpretive Summary:
Technical Abstract: We have previously shown that the chronic wasting disease (CWD) agent from white-tailed deer can be transmitted to domestic pigs via intracranial or oral inoculation although with low attack rates and restricted PrPSc accumulation. The objective of this study was to assess the potential for cross-species transmission of pig-passaged CWD using bioassay in transgenic mice. Transgenic mice expressing human (Tg40), bovine (TgBovXV) or porcine (Tg002) PRNP were inoculated intracranially with 1% brain homogenate from a pig that had been intracranially inoculated with a pool of CWD from white-tailed deer. This pig developed neurological clinical signs, was euthanized at 64 months post-inoculation, and PrPSc was detected in the brain. Mice were monitored daily for clinical signs of disease until the end of the study. Mice were considered positive if PrPSc was detected in the brain using an enzyme immunoassay (EIA). In transgenic mice expressing porcine prion protein the average incubation period was 167 days post-inoculation (dpi) and 3/27 mice were EIA positive (attack rate = 11%). All 3 mice were found dead and clinical signs were not noted prior to death. One transgenic mouse expressing bovine prion protein was euthanized due to excessive scratching at 617 dpi and 2 mice culled at the end of the study at 700 dpi were EIA positive resulting in an overall attack rate of 3/16 (19%). None of the transgenic mice expressing human prion protein that died or were euthanized up to 769 dpi were EIA positive and at study end point at 800 dpi 2 mice had positive EIA results (overall attack rate = 2/20 = 10%). The EIA optical density (OD) readings for all positive mice were at the lower end of the reference range (positive mice range, OD = 0.266-0.438; test positive reference range, OD = 0.250-4.000). To the authors’ knowledge, cervid-derived CWD isolates have not been successfully transmitted to transgenic mice expressing human prion protein. The successful transmission of pig-passaged CWD to Tg40 mice reported here suggests that passage of the CWD agent through pigs results in a change of the transmission characteristics which reduces the transmission barrier of Tg40 mice to the CWD agent. If this biological behavior is recapitulated in the original host species, passage of the CWD agent through pigs could potentially lead to increased pathogenicity of the CWD agent in humans.
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 month group was positive by EIA. PrPSc was detected by QuIC in at least one of the lymphoid tissues examined in 5/6 pigs in the intracranial <6 months group, 6/7 intracranial >6 months group, 5/6 pigs in the oral <6 months group, and 4/6 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.
Research Project: TRANSMISSION, DIFFERENTIATION, AND PATHOBIOLOGY OF TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES
Location: Virus and Prion Research
Title: Disease-associated prion protein detected in lymphoid tissues from pigs challenged with the agent of chronic wasting disease)
Author item Moore, Sarah item Kunkle, Robert item Kondru, Naveen item Manne, Sireesha item Smith, Jodi item Kanthasamy, Anumantha item West Greenlee, M item Greenlee, Justin
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: Chronic wasting disease (CWD) is a naturally-occurring, fatal neurodegenerative disease of cervids. We previously demonstrated that disease-associated prion protein (PrPSc) can be detected in the brain and retina from pigs challenged intracranially or orally with the CWD agent. In that study, neurological signs consistent with prion disease were observed only in one pig: an intracranially challenged pig that was euthanized at 64 months post-challenge. The purpose of this study was to use an antigen-capture immunoassay (EIA) and real-time quaking-induced conversion (QuIC) to determine whether PrPSc is present in lymphoid tissues from pigs challenged with the CWD agent. Methods: At two months of age, crossbred pigs were challenged by the intracranial route (n=20), oral route (n=19), or were left unchallenged (n=9). At approximately 6 months of age, the time at which commercial pigs reach market weight, half of the pigs in each group were culled (<6 month challenge groups). The remaining pigs (>6 month challenge groups) were allowed to incubate for up to 73 months post challenge (mpc). The retropharyngeal lymph node (RPLN) was screened for the presence of PrPSc by EIA and immunohistochemistry (IHC). The RPLN, palatine tonsil, and mesenteric lymph node (MLN) from 6-7 pigs per challenge group were also tested using EIA and QuIC. 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 month group was positive by EIA. PrPSc was detected by QuIC in at least one of the lymphoid tissues examined in 5/6 pigs in the intracranial <6 months group, 6/7 intracranial >6 months group, 5/6 pigs in the oral <6 months group, and 4/6 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.
CONFIDENTIAL
EXPERIMENTAL PORCINE SPONGIFORM ENCEPHALOPATHY
While this clearly is a cause for concern we should not jump to the conclusion that this means that pigs will necessarily be infected by bone and meat meal fed by the oral route as is the case with cattle. ...
we cannot rule out the possibility that unrecognised subclinical spongiform encephalopathy could be present in British pigs though there is no evidence for this: only with parenteral/implantable pharmaceuticals/devices is the theoretical risk to humans of sufficient concern to consider any action.
May I, at the outset, reiterate that we should avoid dissemination of papers relating to this experimental finding to prevent premature release of the information. ...
3. It is particularly important that this information is not passed outside the Department, until Ministers have decided how they wish it to be handled. ...
But it would be easier for us if pharmaceuticals/devices are not directly mentioned at all. ...
Our records show that while some use is made of porcine materials in medicinal products, the only products which would appear to be in a hypothetically ''higher risk'' area are the adrenocorticotrophic hormone for which the source material comes from outside the United Kingdom, namely America China Sweden France and Germany. The products are manufactured by Ferring and Armour. A further product, ''Zenoderm Corium implant'' manufactured by Ethicon, makes use of porcine skin - which is not considered to be a ''high risk'' tissue, but one of its uses is described in the data sheet as ''in dural replacement''. This product is sourced from the United Kingdom.....
snip...
It was not until . . . August 1990, that the result from the pig persuaded both SEAC and us to change our view and to take out of pig rations any residual infectivity that might have arisen from the SBOs.
4.303 The minutes of the meeting record that:
It was very difficult to draw conclusions from one experimental result for what may happen in the field. However it would be prudent to exclude specified bovine offals from the pig diet. Although any relationship between BSE and the finding of a spongiform encephalopathy in cats had yet to be demonstrated, the fact that this had occurred suggested that a cautious view should be taken of those species which might be susceptible. The 'specified offals' of bovines should therefore be excluded from the feed of all species. 17
http://web.archive.org/web/20031026084516/http://www.bseinquiry.gov.uk/files/yb/1990/09/07001001.pdf
IN CONFIENCE
EXPERIMENTAL PORCINE SPONGIFORM ENCEPHALOPATHY
1. CMO should be aware that a pig inoculated experimentally (ic, iv, and ip) with BSE brain suspension has after 15 months developed an illness, now confirmed as a spongiform encephalopathy. This is the first ever description of such a disease in a pig, although it seems there ar no previous attempts at experimental inoculation with animal material. The Southwood group had thought igs would not be susceptible. Most pigs are slaughtered when a few weeks old but there have been no reports of relevant neurological illness in breeding sows or other elderly pigs. ...see full text ;
IN CONFIDENCE
So it is plausible pigs could be preclinically affected with BSE but since so few are allowed to reach adulthood this has not been recognised through clinical disease. ...
CONFIDENTIAL
EXPERIMENTAL PORCINE SPONGIFORM ENCEPHALOPATHY
While this clearly is a cause for concern we should not jump to the conclusion that this means that pigs will necessarily be infected by bone and meat meal fed by the oral route as is the case with cattle. ...
we cannot rule out the possibility that unrecognised subclinical spongiform encephalopathy could be present in British pigs though there is no evidence for this: only with parenteral/implantable pharmaceuticals/devices is the theoretical risk to humans of sufficient concern to consider any action.
May I, at the outset, reiterate that we should avoid dissemination of papers relating to this experimental finding to prevent premature release of the information. ...
3. It is particularly important that this information is not passed outside the Department, until Ministers have decided how they wish it to be handled. ...
But it would be easier for us if pharmaceuticals/devices are not directly mentioned at all. ...
Our records show that while some use is made of porcine materials in medicinal products, the only products which would appear to be in a hypothetically ''higher risk'' area are the adrenocorticotrophic hormone for which the source material comes from outside the United Kingdom, namely America China Sweden France and Germany. The products are manufactured by Ferring and Armour. A further product, ''Zenoderm Corium implant'' manufactured by Ethicon, makes use of porcine skin - which is not considered to be a ''high risk'' tissue, but one of its uses is described in the data sheet as ''in dural replacement''. This product is sourced from the United Kingdom.....
BSE TO PIGS NEWS RELEASE
CONFIDENTIAL
BSE: PRESS PRESENTATION
http://web.archive.org/web/20030820195733/http://www.bseinquiry.gov.uk/files/yb/1990/09/20010001.pdf
http://web.archive.org/web/20030820195733/http://www.bseinquiry.gov.uk/files/yb/1990/09/25013001.pdf
http://web.archive.org/web/20030820195733/http://www.bseinquiry.gov.uk/files/yb/1990/09/25015001.pdf
INDUSTRY RESPONSE TYPICAL
DEFENSIVE BRIEFING
http://web.archive.org/web/20030820195733/http://www.bseinquiry.gov.uk/files/yb/1990/09/25016001.pdf
CONFIDENTIAL
pigs & pharmaceuticals
COMMERCIAL IN CONFIDENCE COMMITTEE ON SAFETY OF MEDICINE NOT FOR PUBLICATION BOVINE SPONGIFORM ENCEPHALOPATHY WORKING GROUP
There are only two products using porcine brain and these use corticotrophin BP, made from porcine pituitary, source from outside the UK.............
snip...
7 OF 10 LITTLE PIGGIES WENT ON TO DEVELOP BSE;
1: J Comp Pathol. 2000 Feb-Apr; 122(2-3): 131-43. Related Articles,
The neuropathology of experimental bovine spongiform encephalopathy in the pig.
Ryder SJ, Hawkins SA, Dawson M, Wells GA.
Veterinary Laboratories Agency Weybridge, Woodham Lane, New Haw, Addlestone, Surrey, KT15 3NB, UK.
In an experimental study of the transmissibility of BSE to the pig, seven of 10 pigs, infected at 1-2 weeks of age by multiple-route parenteral inoculation with a homogenate of bovine brain from natural BSE cases developed lesions typical of spongiform encephalopathy. The lesions consisted principally of severe neuropil vacuolation affecting most areas of the brain, but mainly the forebrain. In addition, some vacuolar change was identified in the rostral colliculi and hypothalamic areas of normal control pigs. PrP accumulations were detected immunocytochemically in the brains of BSE-infected animals. PrP accumulation was sparse in many areas and its density was not obviously related to the degree of vacuolation. The patterns of PrP immunolabelling in control pigs differed strikingly from those in the infected animals.
PMID: 10684682 [PubMed - indexed for MEDLINE]
snip...
In the United States, feeding of ruminant by-products to ruminants is prohibited, but feeding of ruminant materials to swine and poultry still occurs. The potential for swine to have access to scrapie-contaminated feedstuffs exists, but the potential for swine to serve as a host for replication/accumulation of the agent of scrapie is unknown. The purpose of this study was to perform oral and intracerebral inoculation of the U.S. scrapie agent to determine the potential of swine as a host for the scrapie agent and their clinical susceptibility.
see full text and more transmission studies here ;
THURSDAY, JUNE 3, 2021
Porcine Spongiform Encephalopathy PSE TSE Prion disease Spongiform Encephalopathy In Pigs
Tuesday, April 27, 2021
Working Document on Camel Prion Disease (CPrD) 14/09/2020
MONDAY, JUNE 28, 2021
BSE can propagate in sheep co‑infected or pre‑infected with scrapie
TUESDAY, JUNE 8, 2021
Bovine spongiform encephalopathy: the effect of oral exposure dose on attack rate and incubation period in cattle
WEDNESDAY, MARCH 24, 2021
USDA Animal and Plant Health Inspection Service 2020 IMPACT REPORT BSE TSE Prion Testing and Surveillance MIA
***> AS is considered more likely (subjective probability range 50–66%) that AS is a non-contagious, rather than a contagious, disease.
ATYPICAL SCRAPIE ROUGHLY HAS 50 50 CHANCE ATYPICAL SCRAPIE IS CONTAGIOUS, AS NON-CONTAGIOUS, TAKE YOUR PICK, BUT I SAID IT LONG AGO WHEN USDA OIE ET AL MADE ATYPICAL SCRAPIE A LEGAL TRADING COMODITY, I SAID YOUR PUTTING THE CART BEFORE THE HORSE, AND THAT'S EXACTLY WHAT THEY DID, and it's called in Texas, TEXAS TSE PRION HOLDEM POKER, WHO'S ALL IN $$$
THURSDAY, JULY 8, 2021
EFSA Scientific report on the analysis of the 2‐year compulsory intensified monitoring of atypical scrapie
SATURDAY, MAY 29, 2021
Second passage of chronic wasting disease of mule deer to sheep by intracranial inoculation compared to classical scrapie
''Given the results of this study, current diagnostic techniques would be unlikely to distinguish CWD in sheep from scrapie in sheep if cross-species transmission occurred naturally.''
FRIDAY, APRIL 23, 2021
Consultation: Draft VKM order on zoonotic potential in scrapie Singeltary Submission
MONDAY, APRIL 12, 2021
Transmission of the atypical/Nor98 scrapie agent to Suffolk sheep with VRQ/ARQ, ARQ/ARQ, and ARQ/ARR genotypes
WEDNESDAY, FEBRUARY 03, 2021
Scrapie TSE Prion United States of America a Review February 2021 Singeltary et al
SUNDAY, JULY 11, 2021
Animal protein back on the menu in EU
TUESDAY, MAY 11, 2021
A Unique Presentation of Creutzfeldt-Jakob Disease in a Patient Consuming Deer Antler Velvet
Tuesday, December 15, 2020
Risk of Transmissibility From Neurodegenerative Disease-Associated Proteins: Experimental Knowns and Unknowns
THURSDAY, JULY 02, 2020
Variant Creutzfeldt–Jakob Disease Diagnosed 7.5 Years after Occupational Exposure
SATURDAY, AUGUST 01, 2020
Sporadic Creutzfeldt-Jakob Disease among Physicians, Germany, 1993–2018 high proportion of physicians with sCJD were surgeons
SATURDAY, FEBRUARY 20, 2021
Abnormal prion protein deposits with high seeding activities in the skeletal muscle, femoral nerve, and scalp of an autopsied case of sporadic Creutzfeldt–Jakob disease
TUESDAY, DECEMBER 01, 2020
Sporadic Creutzfeldt Jakob Disease sCJD and Human TSE Prion Annual Report December 14, 2020
| VOLUME 20, ISSUE 3, P235-246, MARCH 01, 2021
Biomarkers and diagnostic guidelines for sporadic Creutzfeldt-Jakob disease
Peter Hermann, MD Prof Brian Appleby, MD Jean-Philippe Brandel, MD Byron Caughey, PhD Prof Steven Collins, MD Prof Michael D Geschwind, PhD et al. Show all authors
Published:March, 2021DOI: https://doi.org/10.1016/S1474-4422(20)30477-4
Summary
Sporadic Creutzfeldt-Jakob disease is a fatal neurodegenerative disease caused by misfolded prion proteins (PrPSc). Effective therapeutics are currently not available and accurate diagnosis can be challenging. Clinical diagnostic criteria use a combination of characteristic neuropsychiatric symptoms, CSF proteins 14-3-3, MRI, and EEG. Supportive biomarkers, such as high CSF total tau, could aid the diagnostic process. However, discordant studies have led to controversies about the clinical value of some established surrogate biomarkers. Development and clinical application of disease-specific protein aggregation and amplification assays, such as real-time quaking induced conversion (RT-QuIC), have constituted major breakthroughs for the confident pre-mortem diagnosis of sporadic Creutzfeldt-Jakob disease. Updated criteria for the diagnosis of sporadic Creutzfeldt-Jakob disease, including application of RT-QuIC, should improve early clinical confirmation, surveillance, assessment of PrPSc seeding activity in different tissues, and trial monitoring. Moreover, emerging blood-based, prognostic, and potentially pre-symptomatic biomarker candidates are under investigation.
Diagnosis and Reporting of Creutzfeldt-Jakob Disease
Singeltary, Sr et al. JAMA.2001; 285: 733-734. Vol. 285 No. 6, February 14, 2001 JAMA Diagnosis and Reporting of Creutzfeldt-Jakob Disease
To the Editor:
In their Research Letter, Dr Gibbons and colleagues1 reported that the annual US death rate due to Creutzfeldt-Jakob disease (CJD) has been stable since 1985. These estimates, however, are based only on reported cases, and do not include misdiagnosed or preclinical cases. It seems to me that misdiagnosis alone would drastically change these figures. An unknown number of persons with a diagnosis of Alzheimer disease in fact may have CJD, although only a small number of these patients receive the postmortem examination necessary to make this diagnosis. Furthermore, only a few states have made CJD reportable. Human and animal transmissible spongiform encephalopathies should be reportable nationwide and internationally..
Terry S. Singeltary, Sr Bacliff, Tex
1. Gibbons RV, Holman RC, Belay ED, Schonberger LB. Creutzfeldt-Jakob disease in the United States: 1979-1998. JAMA. 2000;284:2322-2323.
Control of Chronic Wasting Disease OMB Control Number: 0579-0189 APHIS-2021-0004 Singeltary Submission
APHIS-2021-0004-0002
APHIS Concurrence With OIE Risk Designation for Bovine Spongiform Encephalopathy [Docket No. APHIS-2018-0087] Singeltary Submission
June 17, 2019
APHIS Concurrence With OIE Risk Designation for Bovine Spongiform Encephalopathy [Docket No. APHIS-2018-0087] Singeltary Submission
Greetings APHIS et al,
I would kindly like to comment on APHIS Concurrence With OIE Risk Designation for Bovine Spongiform Encephalopathy [Docket No. APHIS-2018-0087], and my comments are as follows, with the latest peer review and transmission studies as references of evidence.
THE OIE/USDA BSE Minimal Risk Region MRR is nothing more than free pass to import and export the Transmissible Spongiform Encephalopathy TSE Prion disease. December 2003, when the USDA et al lost it's supposedly 'GOLD CARD' ie BSE FREE STATUS (that was based on nothing more than not looking and not finding BSE), once the USA lost it's gold card BSE Free status, the USDA OIE et al worked hard and fast to change the BSE Geographical Risk Statuses i.e. the BSE GBR's, and replaced it with the BSE MRR policy, the legal tool to trade mad cow type disease TSE Prion Globally. The USA is doing just what the UK did, when they shipped mad cow disease around the world, except with the BSE MRR policy, it's now legal.
Also, the whole concept of the BSE MRR policy is based on a false pretense, that atypical BSE is not transmissible, and that only typical c-BSE is transmissible via feed. This notion that atypical BSE TSE Prion is an old age cow disease that is not infectious is absolutely false, there is NO science to show this, and on the contrary, we now know that atypical BSE will transmit by ORAL ROUTES, but even much more concerning now, recent science has shown that Chronic Wasting Disease CWD TSE Prion in deer and elk which is rampant with no stopping is sight in the USA, and Scrapie TSE Prion in sheep and goat, will transmit to PIGS by oral routes, this is our worst nightmare, showing even more risk factors for the USA FDA PART 589 TSE PRION FEED ban.
The FDA PART 589 TSE PRION FEED ban has failed terribly bad, and is still failing, since August 1997. there is tonnage and tonnage of banned potential mad cow feed that went into commerce, and still is, with one decade, 10 YEARS, post August 1997 FDA PART 589 TSE PRION FEED ban, 2007, with 10,000,000 POUNDS, with REASON, Products manufactured from bulk feed containing blood meal that was cross contaminated with prohibited meat and bone meal and the labeling did not bear cautionary BSE statement. you can see all these feed ban warning letters and tonnage of mad cow feed in commerce, year after year, that is not accessible on the internet anymore like it use to be, you can see history of the FDA failure August 1997 FDA PART 589 TSE PRION FEED ban here, but remember this, we have a new outbreak of TSE Prion disease in a new livestock species, the camel, and this too is very worrisome.
WITH the OIE and the USDA et al weakening the global TSE prion surveillance, by not classifying the atypical Scrapie as TSE Prion disease, and the notion that they want to do the same thing with typical scrapie and atypical BSE, it's just not scientific.
WE MUST abolish the BSE MRR policy, go back to the BSE GBR risk assessments by country, and enhance them to include all strains of TSE Prion disease in all species. With Chronic Wasting CWD TSE Prion disease spreading in Europe, now including, Norway, Finland, Sweden, also in Korea, Canada and the USA, and the TSE Prion in Camels, the fact the the USA is feeding potentially CWD, Scrapie, BSE, typical and atypical, to other animals, and shipping both this feed and or live animals or even grains around the globe, potentially exposed or infected with the TSE Prion. this APHIS Concurrence With OIE Risk Designation for Bovine Spongiform Encephalopathy [Docket No. APHIS-2018-0087], under it's present definition, does NOT show the true risk of the TSE Prion in any country. as i said, it's nothing more than a legal tool to trade the TSE Prion around the globe, nothing but ink on paper.
AS long as the BSE MRR policy stays in effect, TSE Prion disease will continued to be bought and sold as food for both humans and animals around the globe, and the future ramifications from friendly fire there from, i.e. iatrogenic exposure and transmission there from from all of the above, should not be underestimated. ...
Saturday, May 1, 2021
Clinical Use of Improved Diagnostic Testing for Detection of Prion Disease
MONDAY, JUNE 14, 2021
Texas Health and Human Services The Department of State Health Services Creutzfeldt Jakob Disease TSE Prion Report 2021?
Thursday, June 24, 2021
34 year old Doctor Orthopedic Surgeon dies from CJD, what about iatrogenic CJD?
wasted days and wasted nights...Freddy Fender
stupid is as stupid does...Forest Gump
Terry S. Singeltary Sr.
No comments:
Post a Comment
Note: Only a member of this blog may post a comment.