Sheep and Goat BSE Propagate More Efficiently than Cattle BSE in Human PrP Transgenic Mice

Sheep and Goat BSE Propagate More Efficiently than Cattle BSE in Human PrP Transgenic Mice


Danielle Padilla1#, Vincent Béringue2#, Juan Carlos Espinosa1, Olivier Andreoletti3, Emilie Jaumain2, Fabienne Reine2, Laetitia Herzog2, Alfonso Gutierrez-Adan4, Belen Pintado4, Hubert Laude2, Juan Maria Torres1*

1 Centro de Investigación en Sanidad Animal (CISA-INIA), Madrid, Spain, 2 INRA, UR892, Virologie Immunologie Moléculaires, Jouy-en-Josas, France, 3 UMR INRA-ENVT 1225, Interactions Hôte Agent Pathogène, Ecole Nationale Vétérinaire de Toulouse, Toulouse, France, 4 Departamento de Reproducción Animal-INIA, Madrid, Spain

Abstract Top A new variant of Creutzfeldt Jacob Disease (vCJD) was identified in humans and linked to the consumption of Bovine Spongiform Encephalopathy (BSE)-infected meat products. Recycling of ruminant tissue in meat and bone meal (MBM) has been proposed as origin of the BSE epidemic. During this epidemic, sheep and goats have been exposed to BSE-contaminated MBM. It is well known that sheep can be experimentally infected with BSE and two field BSE-like cases have been reported in goats. In this work we evaluated the human susceptibility to small ruminants-passaged BSE prions by inoculating two different transgenic mouse lines expressing the methionine (Met) allele of human PrP at codon 129 (tg650 and tg340) with several sheep and goat BSE isolates and compared their transmission characteristics with those of cattle BSE. While the molecular and neuropathological transmission features were undistinguishable and similar to those obtained after transmission of vCJD in both transgenic mouse lines, sheep and goat BSE isolates showed higher transmission efficiency on serial passaging compared to cattle BSE. We found that this higher transmission efficiency was strongly influenced by the ovine PrP sequence, rather than by other host species-specific factors. Although extrapolation of results from prion transmission studies by using transgenic mice has to be done very carefully, especially when human susceptibility to prions is analyzed, our results clearly indicate that Met129 homozygous individuals might be susceptible to a sheep or goat BSE agent at a higher degree than to cattle BSE, and that these agents might transmit with molecular and neuropathological properties indistinguishable from those of vCJD. Our results suggest that the possibility of a small ruminant BSE prion as vCJD causal agent could not be ruled out, and that the risk for humans of a potential goat and/or sheep BSE agent should not be underestimated.

Author Summary Top Prion diseases, also referred as transmissible spongiform encephalopathies, are fatal neurodegenerative diseases caused by proteinaceous infectious particles denominated “prions.” Prion diseases acquired their first real public relevance with the outbreak of bovine spongiform encephalopathy (BSE) (“mad cow disease”) in the United Kingdom in the 80s and its link with the appearance of a new, variant form of Creutzfeldt-Jakob disease in humans. Recycling of ruminant tissues in meat and bone meal has been proposed as origin of the BSE epidemic. During this episode, sheep and goats have also been exposed to BSE-contaminated meal, so transmission to this species may have occurred. We analyzed the human susceptibility to sheep and goat passaged-BSE prions by using transgenic mice expressing human prion protein (PrP). When different sheep and goat BSE isolates were inoculated in these transgenic mice, higher susceptibility than that observed for cattle BSE was detected and the disease manifestation was similar to that observed in mice inoculated with the new variant of Creutzfeldt-Jakob disease. Our findings suggest that humans are at least equally, and might be even more, susceptible to a sheep or goat BSE agent compared to a cattle BSE one.

snip...

Discussion Top In this study, we compared the transmission features of cattle and sheep/goat BSE prions in two different models of transgenic mice expressing Met129 human PrP (tg650 and tg340 lines) in two different laboratories. In general, the transmission results obtained in both human-PrP transgenic mouse lines were very comparable. Some shortening in survival times was observed in tg650 mice (compared to the tg340 mice line), which was probably due to higher PrP expression levels in this line. Worryingly, our results support the view that an intermediate passage of BSE agent in small ruminants accelerates the appearance of a vCJD-like disease in human PrP mice or markedly increases its transmission efficiency. Because the apparent phenotype of cattle and sheep/goat BSE prions is conserved, these data also unravel an important role of PrPSc primary sequence in the cross-species transmission capacities of prion strains.

The transmission efficiency of cattle BSE isolates in both human-PrP transgenic mouse models was apparently low. With all BSE isolates, whose high infectivity has been demonstrated in bovine-PrP transgenic mice (Tables 2 and 3), very low attack rates were obtained on primary transmission to both tg650 and tg340 mice. Three passages were necessary to achieve a degree of fitness comparable to vCJD in the same mouse line. This low BSE transmission efficiency to human PrP transgenic mice -occasionally accompanied by a strain shift- has also been described by others [40], [41], [42], and suggests a strong although not absolute transmission barrier. Although the exact characteristics and further evolution of the vCJD epidemic still entail uncertainties owing to prolonged incubation times, this apparent high transmission barrier of humans to cattle BSE might be an explanation for the currently low vCJD incidence, considering the high exposure to BSE during the “mad cow” crisis.

Remarkably, a different picture emerged when the sheep and goat BSE isolates were inoculated to human PrP transgenic mouse models. Attack rates approaching 100% were observed from the primary passage onwards and mean incubation times were more consistent with those measured after transmission of vCJD. On further passaging, the neuropathological phenotype and PrPSc type of cattle and sheep/goat BSE agents appeared indistinguishable from the vCJD agent propagated in these mice, as previously demonstrated in bovine transgenic mice [29], thus strongly supporting the view that the same BSE prion strain has been propagated whatever the infecting species. Hence, these observations reproduced in two distinct human transgenic lines with different genetic background and PrP expression levels support the view that transmission efficiency of BSE prions is increased by an intermediate passage in sheep or goat. Although the electrophoretic pattern of sheep/goat and cattle BSE PrPres appeared similar in human-PrP transgenic mice, other assays are currently performed to further compare the biochemical or biophysical properties of the respective proteins are ongoing.

Importantly, the higher attack rates obtained after sheep and goat BSE transmissions compared to cattle BSE are not in accordance with the initial PrPres content of these isolates. In addition, the data from inoculation to BoPrP-Tg reporter mice suggest that cattle BSE and sheep and goat-BSE isolates could have similar transmission efficiency (Table 1 and 2) in the absence of apparent transmission barrier [36]. Furthermore, when the human PrP transgenic lines were inoculated with the BSE agent passaged into bovine and ovine transgenic mice, the transmission results were comparable to those of the cattle and sheep BSE isolates (Figure 7), further supporting the crucial role of the PrPSc primary sequence in the increase of transmission efficiency. Taken together all these considerations suggest that the higher transmission efficiency of sheep and goat BSE isolates in comparison to cattle BSE isolates cannot be linked to a higher infectious titer of the inoculum but must be the outcome of a modification in the pathogenicity of the agent.

Commonly, transmission barriers are determined considering attack rates and quantified by measuring the fall in the mean survival times between the first and second passage. Hence, if we consider PrPres detection as an indicator of successful transmission, our results imply that humans could be significantly more susceptible to a sheep or goat BSE agent than to a cattle BSE agent. On the other hand our results suggest that cattle BSE infection could produce very long latency in humans, with conversion efficiency far below the threshold of detectable PrPres, which is also very worrying since it suggests the possibility of silent carriers.

Our observations, made in two different mouse genetic backgrounds, suggest that the different transmission properties acquired by BSE after passage into either sheep or transgenic mice expressing ovine PrP are strongly related to the ovine PrP primary sequence, rather than to other host species-specific factors. Thus the transmission barrier observed with cattle BSE was fully restored when sheep/goat BSE experienced intermediate passaging into bovine transgenic mice before reinoculation to human PrP mice. In contrast, when the ovine sequence of sheep BSE was maintained, through passage into ARQ ovine PrP transgenic mice, the efficient transmission to human PrP mice was maintained. Apparently, an ovine/caprine PrPSc sequence appears to facilitate human PrP conversion by the BSE agent, compared to a bovine one.

The PrP primary sequence influence seems to depend strongly on the strain involved, since no PrPres was found in either first or second passages of sheep scrapie in tg340 mice (unpublished observations), suggesting no infection, in accordance with the lack of epidemiological evidence linking scrapie with human TSE. Moreover, the low transmission efficiency observed for the cattle BSE agent is not exclusively linked to the bovine PrP sequence since other uncommon BSE strains (BSE-L) are efficiently transmitted to human-PrP mice [41], [43]. Considering the conformational selection model [20], our results would suggest that M129 human PrPC prefers a BSE PrPSc with conformational characteristics templated by the ovine sequence, to a bovine BSE PrPSc. Because a similar increased transmission efficiency of sheep/goat BSE has been reported in wild type mice [44] and transgenic mice expressing elk [45], bovine [29] and porcine [30] PrP, the better structural compatibility conferred by sheep/goat primary PrPSc sequence may not be limited to human PrPC. One explanation might be an alteration in the quaternary structure (after passage into sheep/goat) generating PrPSc polymers less degraded or more rapidly/easily amplified favouring or enhancing the initial conversion. This question is currently being addressed by sedimentation velocity [46] and PMCA experiments. Another possibility, within the quasispecies concept [20], [47], might be that BSE prions confrontation with the sheep and goat primary PrP sequence increases the variety of BSE substrain components, with the following emergence of a markedly adapted component in response to the selection pressure imposed by the interspecies transmission events. On the other hand, this component would not be distinguishable from bovine-passaged BSE prions due to the current limits of the standard biological methods and/or the molecular tools employed here to characterize prion strains. Whatever the mechanism, the notion that a passage through an intermediate species can profoundly alter prion virulence for the human species has important public-health issues, regarding emerging and/or expanding TSEs, like atypical scrapie or CWD.

Although extrapolation of results from prion transmission studies by using transgenic mice has to be done very carefully, especially when human susceptibility to prions is analyzed, our results clearly indicate that Met129 homozygous individuals might be susceptible to a sheep or goat BSE agent at a higher degree than to cattle BSE, and that these agents might transmit with molecular and neuropathological properties indistinguishable from those of vCJD. Although no vCJD cases have been described in Val129 homozygous individuals so far it is relevant to analyze if similar results will be observed in this genotype. This issue is currently being addressed in transmission experiments using transgenic mice expressing Val129 human PrP.

Taken all together, our results suggest that the possibility of a small ruminant BSE prion as vCJD causal agent could not be ruled out, which has important implications on public and animal health policies. On one hand, although the exact magnitude and characteristic of the vCJD epidemic is still unclear, its link with cattle BSE is supported by strong epidemiological ground and several experimental data. On the other hand, the molecular typing performed in our studies, indicates that the biochemical characteristics of the PrPres detected in brains of our sheep and goat BSE-inoculated mice seem to be indistinguishable from that observed in vCJD. Considering the similarity in clinical manifestation of BSE- and scrapie-affected sheep [48], a masker effect of scrapie over BSE, as well as a potential adaptation of the BSE agent through subsequent passages, could not be ruled out. As BSE infected sheep PrPSc have been detected in many peripheral organs, small ruminant-passaged BSE prions might be a more widespread source of BSE infectivity compared to cattle [19], [49], [50]. This fact is even more worrying since our transmission studies suggest that apparently Met129 human PrP favours a BSE agent with ovine rather than a bovine sequence. Finally, it is evident that, although few natural cases have been described and so far we cannot draw any definitive conclusion about the origin of vCJD, we can not underestimate the risk of a potential goat and/or sheep BSE agent.

Citation: Padilla D, Béringue V, Espinosa JC, Andreoletti O, Jaumain E, et al. (2011) Sheep and Goat BSE Propagate More Efficiently than Cattle BSE in Human PrP Transgenic Mice. PLoS Pathog 7(3): e1001319. doi:10.1371/journal.ppat.1001319

Editor: Umberto Agrimi, Istituto Superiore di Sanità, Italy

Received: August 24, 2010; Accepted: February 15, 2011; Published: March 17, 2011

Copyright: © 2011 Padilla et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Funding: This work was supported by grants from European Union (CT-2001-01309, CT2004-023183 and CT2005-036353), Spanish Ministerio de Ciencia e Inovacion (RTA2006-00091) and from UK Food Standards Agency (M03043). D.P. was supported by a fellowship from the Alßan Program. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors have declared that no competing interests exist.

* E-mail: jmtorres@inia.es

# These authors contributed equally to this work.


http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1001319



AGAIN, MANY THANKS to PLOS for the free full text open access !

MANY THANKS to the Authors of this Study.

NOW, let's look at past history on this important human health topic ;


Friday, February 11, 2011

Atypical/Nor98 Scrapie Infectivity in Sheep Peripheral Tissues

http://nor-98.blogspot.com/2011/02/atypicalnor98-scrapie-infectivity-in.html


Sunday, December 12, 2010

EFSA reviews BSE/TSE infectivity in small ruminant tissues News Story 2 December 2010

http://transmissiblespongiformencephalopathy.blogspot.com/2010/12/efsa-reviews-bsetse-infectivity-in.html


Thursday, December 23, 2010

Molecular Typing of Protease-Resistant Prion Protein in Transmissible Spongiform Encephalopathies of Small Ruminants, France, 2002-2009 Volume 17, Number 1 January 2011

http://transmissiblespongiformencephalopathy.blogspot.com/2010/12/molecular-typing-of-protease-resistant.html


Thursday, November 18, 2010

Increased susceptibility of human-PrP transgenic mice to bovine spongiform encephalopathy following passage in sheep

http://bse-atypical.blogspot.com/2010/11/increased-susceptibility-of-human-prp.html


Monday, November 22, 2010

SHEEP WITH MASTITIS TRANSMIT INFECTIOUS PRIONS THROUGH THE MILK

http://scrapie-usa.blogspot.com/2010/11/sheep-with-mastitis-transmit-infectious.html


Published online ahead of print on 26 January 2011 as doi:10.1099/vir.0.028886-0 J Gen Virol (2011), DOI 10.1099/vir.0.028886-0 © 2011 Society for General Microbiology This Article

Emergence of multiple prion strains from single isolates of ovine scrapie

Alana M. Thackray1, Lee Hopkins1, Richard Lockey2, John Spiropoulos2 and Raymond Bujdoso1,3

1 University of Cambridge; 2 VLA, Weybridge

3 E-mail: rb202@cam.ac.uk

The infectious agent associated with prion diseases such as ovine scrapie shows strain diversity. Ovine prion strains have typically been identified by their transmission properties in wild type mice. However, strain typing ovine scrapie isolates in wild type mice may not reveal properties of the infectious prion agent as they exist in the original host. This could be circumvented if ovine scrapie isolates are passaged in ovine PrP transgenic mice. Here we have used incubation time, lesion profile, PrPSc immunohistochemistry and molecular profile to compare the range of ovine prion strains that emerge from sheep scrapie isolates following serial passage in wild type and ovine PrP transgenic mice. We have found that a diverse range of ovine prion strains emerged from homozygous ARQ and VRQ scrapie isolates passaged in wild type and ovine PrP transgenic mice. However, strain-specific PrPSc deposition and PrP27-30 molecular profile patterns were identified in ovine PrP transgenic mice that were not detected in wild type mice. Significantly, we have established that the individual mouse brain selected for transmission during prion strain typing has a significant influence on strain definition. Serial passage of short and long incubation time animals from the same group of scrapie inoculated mice revealed different prion strain phenotypes. Our observations are consistent with the possibility that some scrapie isolates contained more than one prion strain.

Received 10 November 2010; accepted 24 January 2011.

http://vir.sgmjournals.org/cgi/content/abstract/vir.0.028886-0v1


Wednesday, January 19, 2011

EFSA and ECDC review scientific evidence on possible links between TSEs in animals and humans Webnachricht 19 Januar 2011

http://transmissiblespongiformencephalopathy.blogspot.com/2011/01/efsa-and-ecdc-review-scientific.html


Saturday, December 18, 2010

OIE Global Conference on Wildlife Animal Health and Biodiversity – Preparing for the Future (TSE AND PRIONS) Paris (France), 23-25 February 2011

SNIP...

please see full text ;

http://transmissiblespongiformencephalopathy.blogspot.com/2010/12/oie-global-conference-on-wildlife.html


Tuesday, April 28, 2009

Nor98-like Scrapie in the United States of America

http://nor-98.blogspot.com/2009/04/nor98-like-scrapie-in-united-states-of.html


Wednesday, March 3, 2010

NOR-98 ATYPICAL SCRAPIE USA 4 CASES DETECTED JANUARY 2010

http://nor-98.blogspot.com/2010/03/nor-98-atypical-scrapie-usa-4-cases.html


P03.141

Aspects of the Cerebellar Neuropathology in Nor98

Gavier-Widén, D1; Benestad, SL2; Ottander, L1; Westergren, E1 1National Veterinary Insitute, Sweden; 2National Veterinary Institute,

Norway Nor98 is a prion disease of old sheep and goats. This atypical form of scrapie was first described in Norway in 1998. Several features of Nor98 were shown to be different from classical scrapie including the distribution of disease associated prion protein (PrPd) accumulation in the brain. The cerebellum is generally the most affected brain area in Nor98. The study here presented aimed at adding information on the neuropathology in the cerebellum of Nor98 naturally affected sheep of various genotypes in Sweden and Norway. A panel of histochemical and immunohistochemical (IHC) stainings such as IHC for PrPd, synaptophysin, glial fibrillary acidic protein, amyloid, and cell markers for phagocytic cells were conducted. The type of histological lesions and tissue reactions were evaluated. The types of PrPd deposition were characterized. The cerebellar cortex was regularly affected, even though there was a variation in the severity of the lesions from case to case. Neuropil vacuolation was more marked in the molecular layer, but affected also the granular cell layer. There was a loss of granule cells. Punctate deposition of PrPd was characteristic. It was morphologically and in distribution identical with that of synaptophysin, suggesting that PrPd accumulates in the synaptic structures. PrPd was also observed in the granule cell layer and in the white matter. The pathology features of Nor98 in the cerebellum of the affected sheep showed similarities with those of sporadic Creutzfeldt-Jakob disease in humans.

***The pathology features of Nor98 in the cerebellum of the affected sheep showed similarities with those of sporadic Creutzfeldt-Jakob disease in humans.

http://www.prion2007.com/pdf/Prion%20Book%20of%20Abstracts.pdf


PR-26

NOR98 SHOWS MOLECULAR FEATURES REMINISCENT OF GSS

R. Nonno1, E. Esposito1, G. Vaccari1, E. Bandino2, M. Conte1, B. Chiappini1, S. Marcon1, M. Di Bari1, S.L. Benestad3, U. Agrimi1 1 Istituto Superiore di Sanità, Department of Food Safety and Veterinary Public Health, Rome, Italy (romolo.nonno@iss.it); 2 Istituto Zooprofilattico della Sardegna, Sassari, Italy; 3 National Veterinary Institute, Department of Pathology, Oslo, Norway

Molecular variants of PrPSc are being increasingly investigated in sheep scrapie and are generally referred to as "atypical" scrapie, as opposed to "classical scrapie". Among the atypical group, Nor98 seems to be the best identified. We studied the molecular properties of Italian and Norwegian Nor98 samples by WB analysis of brain homogenates, either untreated, digested with different concentrations of proteinase K, or subjected to enzymatic deglycosylation. The identity of PrP fragments was inferred by means of antibodies spanning the full PrP sequence. We found that undigested brain homogenates contain a Nor98-specific PrP fragment migrating at 11 kDa (PrP11), truncated at both the C-terminus and the N-terminus, and not N-glycosylated. After mild PK digestion, Nor98 displayed full-length PrP (FL-PrP) and N-glycosylated C-terminal fragments (CTF), along with increased levels of PrP11. Proteinase K digestion curves (0,006-6,4 mg/ml) showed that FL-PrP and CTF are mainly digested above 0,01 mg/ml, while PrP11 is not entirely digested even at the highest concentrations, similarly to PrP27-30 associated with classical scrapie. Above 0,2 mg/ml PK, most Nor98 samples showed only PrP11 and a fragment of 17 kDa with the same properties of PrP11, that was tentatively identified as a dimer of PrP11. Detergent solubility studies showed that PrP11 is insoluble in 2% sodium laurylsorcosine and is mainly produced from detergentsoluble, full-length PrPSc. Furthermore, among Italian scrapie isolates, we found that a sample with molecular and pathological properties consistent with Nor98 showed plaque-like deposits of PrPSc in the thalamus when the brain was analysed by PrPSc immunohistochemistry. Taken together, our results show that the distinctive pathological feature of Nor98 is a PrP fragment spanning amino acids ~ 90-155. This fragment is produced by successive N-terminal and C-terminal cleavages from a full-length and largely detergent-soluble PrPSc, is produced in vivo and is extremely resistant to PK digestion.

*** Intriguingly, these conclusions suggest that some pathological features of Nor98 are reminiscent of Gerstmann-Sträussler-Scheinker disease.

119

http://www.neuroprion.com/pdf_docs/conferences/prion2006/abstract_book.pdf


A newly identified type of scrapie agent can naturally infect sheep with resistant PrP genotypes

Annick Le Dur*,?, Vincent Béringue*,?, Olivier Andréoletti?, Fabienne Reine*, Thanh Lan Laï*, Thierry Baron§, Bjørn Bratberg¶, Jean-Luc Vilotte?, Pierre Sarradin**, Sylvie L. Benestad¶, and Hubert Laude*,? +Author Affiliations

*Virologie Immunologie Moléculaires and ?Génétique Biochimique et Cytogénétique, Institut National de la Recherche Agronomique, 78350 Jouy-en-Josas, France; ?Unité Mixte de Recherche, Institut National de la Recherche Agronomique-Ecole Nationale Vétérinaire de Toulouse, Interactions Hôte Agent Pathogène, 31066 Toulouse, France; §Agence Française de Sécurité Sanitaire des Aliments, Unité Agents Transmissibles Non Conventionnels, 69364 Lyon, France; **Pathologie Infectieuse et Immunologie, Institut National de la Recherche Agronomique, 37380 Nouzilly, France; and ¶Department of Pathology, National Veterinary Institute, 0033 Oslo, Norway

***Edited by Stanley B. Prusiner, University of California, San Francisco, CA (received for review March 21, 2005)

Abstract Scrapie in small ruminants belongs to transmissible spongiform encephalopathies (TSEs), or prion diseases, a family of fatal neurodegenerative disorders that affect humans and animals and can transmit within and between species by ingestion or inoculation. Conversion of the host-encoded prion protein (PrP), normal cellular PrP (PrPc), into a misfolded form, abnormal PrP (PrPSc), plays a key role in TSE transmission and pathogenesis. The intensified surveillance of scrapie in the European Union, together with the improvement of PrPSc detection techniques, has led to the discovery of a growing number of so-called atypical scrapie cases. These include clinical Nor98 cases first identified in Norwegian sheep on the basis of unusual pathological and PrPSc molecular features and "cases" that produced discordant responses in the rapid tests currently applied to the large-scale random screening of slaughtered or fallen animals. Worryingly, a substantial proportion of such cases involved sheep with PrP genotypes known until now to confer natural resistance to conventional scrapie. Here we report that both Nor98 and discordant cases, including three sheep homozygous for the resistant PrPARR allele (A136R154R171), efficiently transmitted the disease to transgenic mice expressing ovine PrP, and that they shared unique biological and biochemical features upon propagation in mice. *** These observations support the view that a truly infectious TSE agent, unrecognized until recently, infects sheep and goat flocks and may have important implications in terms of scrapie control and public health.

http://www.pnas.org/content/102/44/16031.abstract


Monday, December 1, 2008

When Atypical Scrapie cross species barriers

Authors

Andreoletti O., Herva M. H., Cassard H., Espinosa J. C., Lacroux C., Simon S., Padilla D., Benestad S. L., Lantier F., Schelcher F., Grassi J., Torres, J. M., UMR INRA ENVT 1225, Ecole Nationale Veterinaire de Toulouse.France; ICISA-INlA, Madrid, Spain; CEA, IBiTec-5, DSV, CEA/Saclay, Gif sur Yvette cedex, France; National Veterinary Institute, Postboks 750 Sentrum, 0106 Oslo, Norway, INRA IASP, Centre INRA de Tours, 3738O Nouzilly, France.

Content

Atypical scrapie is a TSE occurring in small ruminants and harbouring peculiar clinical, epidemiological and biochemical properties. Currently this form of disease is identified in a large number of countries. In this study we report the transmission of an atypical scrapie isolate through different species barriers as modeled by transgenic mice (Tg) expressing different species PRP sequence.

The donor isolate was collected in 1995 in a French commercial sheep flock. inoculation into AHQ/AHQ sheep induced a disease which had all neuro-pathological and biochemical characteristics of atypical scrapie. Transmitted into Transgenic mice expressing either ovine or PrPc, the isolate retained all the described characteristics of atypical scrapie.

Surprisingly the TSE agent characteristics were dramatically different v/hen passaged into Tg bovine mice. The recovered TSE agent had biological and biochemical characteristics similar to those of atypical BSE L in the same mouse model. Moreover, whereas no other TSE agent than BSE were shown to transmit into Tg porcine mice, atypical scrapie was able to develop into this model, albeit with low attack rate on first passage.

Furthermore, after adaptation in the porcine mouse model this prion showed similar biological and biochemical characteristics than BSE adapted to this porcine mouse model. Altogether these data indicate.

(i) the unsuspected potential abilities of atypical scrapie to cross species barriers

(ii) the possible capacity of this agent to acquire new characteristics when crossing species barrier

These findings raise some interrogation on the concept of TSE strain and on the origin of the diversity of the TSE agents and could have consequences on field TSE control measures.

http://www.neuroprion.org/resources/pdf_docs/conferences/prion2008/abstract-book-prion2008.pdf


Tuesday, April 28, 2009

Nor98-like Scrapie in the United States of America

http://nor-98.blogspot.com/2009/04/nor98-like-scrapie-in-united-states-of.html


Sunday, April 18, 2010

SCRAPIE AND ATYPICAL SCRAPIE TRANSMISSION STUDIES A REVIEW 2010

http://scrapie-usa.blogspot.com/2010/04/scrapie-and-atypical-scrapie.html


Scrapie USA

http://scrapie-usa.blogspot.com/


Sunday, March 28, 2010

Nor-98 atypical Scrapie, atypical BSE, spontaneous TSE, trade policy, sound science ?

http://nor-98.blogspot.com/2010/03/nor-98-atypical-scrapie-atypical-bse.html


Sunday, October 3, 2010

Scrapie, Nor-98 atypical Scrapie, and BSE in sheep and goats North America, who's looking ?

http://nor-98.blogspot.com/2010/10/scrapie-nor-98-atypical-scrapie-and-bse.html


http://nor-98.blogspot.com/


Monday, December 14, 2009

Similarities between Forms of Sheep Scrapie and Creutzfeldt-Jakob Disease Are Encoded by Distinct Prion Types

(hmmm, this is getting interesting now...TSS)

Sporadic CJD type 1 and atypical/ Nor98 scrapie are characterized by fine (reticular) deposits,

see also ;

All of the Heidenhain variants were of the methionine/ methionine type 1 molecular subtype.

http://cjdusa.blogspot.com/2009/09/co-existence-of-scrapie-prion-protein.html


see full text ;

Monday, December 14, 2009

Similarities between Forms of Sheep Scrapie and Creutzfeldt-Jakob Disease Are Encoded by Distinct Prion Types

http://nor-98.blogspot.com/2009/12/similarities-between-forms-of-sheep.html


Wednesday, February 16, 2011

IN CONFIDENCE SCRAPIE TRANSMISSION TO CHIMPANZEES

IN CONFIDENCE

http://scrapie-usa.blogspot.com/2011/02/in-confidence-scrapie-transmission-to.html


Friday, February 04, 2011

NMLB and USDA allow scrapie prion infected mutton to enter food chain on the Navajo Reservation in New Mexico

http://scrapie-usa.blogspot.com/2011/02/nmlb-and-usda-allow-scrapie-prion.html


Tuesday, February 01, 2011

Sparse PrP-Sc accumulation in the placentas of goats with naturally acquired scrapie

Research article

snip...


Conclusions In this study, PrPSc was detected in some but not all placentomes from naturally infected goats using a sensitive western blot assay. PrPSc detectable by IHC was sparsely distributed in caprine cotyledons and ELISA values were lower than observed with most ovine cotyledons. In spite of the poorly defined effects of PRNP genetics, scrapie strain, dose, route and source of infection, the caprine placenta may represent a source of infection to progeny and herd mates as well as a source of persistent environmental contamination. Caprine scrapie is rarely reported in the US and additional studies using experimentally infected goats may be useful in determining the role of the placenta in transmission of caprine scrapie.

http://www.biomedcentral.com/1746-6148/7/7/abstract


http://www.biomedcentral.com/content/pdf/1746-6148-7-7.pdf



" In spite of the poorly defined effects of PRNP genetics, scrapie strain, dose, route and source of infection, the caprine placenta may represent a source of infection to progeny and herd mates as well as a source of persistent environmental contamination. "


Could this route of infection be the cause of the many cases of Goat scrapie from the same herd in Michigan USA ?

Has this been investigated ?

(Figure 6) including five goat cases in FY 2008 that originated from the same herd in Michigan. This is highly unusual for goats, and I strenuously urge that there should be an independent investigation into finding the common denominator for these 5 goats in the same herd in Michigan with Scrapie. ...

Kind Regards, Terry


Scrapie Nor-98 like case in California FY 2011 AS of December 31, 2010.

Scrapie cases in goats FY 2002 - 2011 AS of December 31, 2010 Total goat cases = 21 Scrapie cases, 0 Nor-98 like Scrapie cases (21 field cases, 0 RSSS cases)

Last herd with infected goats disignated in FY 2008 Michigan 8 cases

http://www.aphis.usda.gov/animal_health/animal_diseases/scrapie/downloads/monthly_scrapie_rpt.pps


UPDATED RESPONSE ON MY CONCERNS OF GOAT SCRAPIE IN MICHIGAN ;


----- Original Message -----

From: "BioMed Central Comments"

To:

Sent: Wednesday, February 16, 2011 4:13 AM

Subject: Your comment on BMC Veterinary Research 2011, 7:7

Your discussion posting "Scrapie cases Goats from same herd USA Michigan" has been rejected by the moderator as not being appropriate for inclusion on the site.

Dear Mr Singeltary,

Thank you for submitting your comment on BMC Veterinary Research article (2011, 7:7). We have read your comment with interest but we feel that only the authors of the article can answer your question about further investigation of the route of infection of the five goats in Michigan. We advise that you contact the authors directly rather than post a comment on the article.

With best wishes,

Maria

Maria Kowalczuk, PhD Deputy Biology Editor BMC-series Journals

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Thursday, January 07, 2010

Scrapie and Nor-98 Scrapie November 2009 Monthly Report Fiscal Year 2010 and FISCAL YEAR 2008

http://scrapie-usa.blogspot.com/2010/01/scrapie-and-nor-98-scrapie-november.html


In FY 2010, 72 cases of classical Scrapie and 5 cases of Nor-98 like Scrapie were confirmed...

http://www.aphis.usda.gov/animal_health/animal_diseases/scrapie/downloads/yearly_report.ppsx


Scrapie Nor-98 like case in California FY 2011 AS of December 31, 2010.

Scrapie cases in goats FY 2002 - 2011 AS of December 31, 2010 Total goat cases = 21 Scrapie cases, 0 Nor-98 like Scrapie cases (21 field cases, 0 RSSS cases)

Last herd with infected goats disignated in FY 2008 Michigan 8 cases

http://www.aphis.usda.gov/animal_health/animal_diseases/scrapie/downloads/monthly_scrapie_rpt.pps


Thursday, November 18, 2010

Increased susceptibility of human-PrP transgenic mice to bovine spongiform encephalopathy following passage in sheep

http://bse-atypical.blogspot.com/2010/11/increased-susceptibility-of-human-prp.html


snip... see full text ;

http://scrapie-usa.blogspot.com/2011/02/sparse-prp-sc-accumulation-in-placentas.html



2001


Suspect symptoms

What if you can catch old-fashioned CJD by eating meat from a sheep infected with scrapie?

28 Mar 2001

Like lambs to the slaughter

31 March 2001

by Debora MacKenzie Magazine issue 2284.

FOUR years ago, Terry Singeltary watched his mother die horribly from a degenerative brain disease. Doctors told him it was Alzheimer's, but Singeltary was suspicious. The diagnosis didn't fit her violent symptoms, and he demanded an autopsy. It showed she had died of sporadic Creutzfeldt-Jakob disease.

Most doctors believe that sCJD is caused by a prion protein deforming by chance into a killer. But Singeltary thinks otherwise. He is one of a number of campaigners who say that some sCJD, like the variant CJD related to BSE, is caused by eating meat from infected animals. Their suspicions have focused on sheep carrying scrapie, a BSE-like disease that is widespread in flocks across Europe and North America.

Now scientists in France have stumbled across new evidence that adds weight to the campaigners' fears. To their complete surprise, the researchers found that one strain of scrapie causes the same brain damage in mice as sCJD.

"This means we cannot rule out that at least some sCJD may be caused by some strains of scrapie," says team member Jean-Philippe Deslys of the French Atomic Energy Commission's medical research laboratory in Fontenay-aux-Roses, south-west of Paris. Hans Kretschmar of the University of Göttingen, who coordinates CJD surveillance in Germany, is so concerned by the findings that he now wants to trawl back through past sCJD cases to see if any might have been caused by eating infected mutton or lamb.

Scrapie has been around for centuries and until now there has been no evidence that it poses a risk to human health. But if the French finding means that scrapie can cause sCJD in people, countries around the world may have overlooked a CJD crisis to rival that caused by BSE.

Deslys and colleagues were originally studying vCJD, not sCJD. They injected the brains of macaque monkeys with brain from BSE cattle, and from French and British vCJD patients. The brain damage and clinical symptoms in the monkeys were the same for all three. Mice injected with the original sets of brain tissue or with infected monkey brain also developed the same symptoms.

As a control experiment, the team also injected mice with brain tissue from people and animals with other prion diseases: a French case of sCJD; a French patient who caught sCJD from human-derived growth hormone; sheep with a French strain of scrapie; and mice carrying a prion derived from an American scrapie strain. As expected, they all affected the brain in a different way from BSE and vCJD. But while the American strain of scrapie caused different damage from sCJD, the French strain produced exactly the same pathology.

"The main evidence that scrapie does not affect humans has been epidemiology," says Moira Bruce of the neuropathogenesis unit of the Institute for Animal Health in Edinburgh, who was a member of the same team as Deslys. "You see about the same incidence of the disease everywhere, whether or not there are many sheep, and in countries such as New Zealand with no scrapie." In the only previous comparisons of sCJD and scrapie in mice, Bruce found they were dissimilar.

But there are more than 20 strains of scrapie, and six of sCJD. "You would not necessarily see a relationship between the two with epidemiology if only some strains affect only some people," says Deslys. Bruce is cautious about the mouse results, but agrees they require further investigation. Other trials of scrapie and sCJD in mice, she says, are in progress.

People can have three different genetic variations of the human prion protein, and each type of protein can fold up two different ways. Kretschmar has found that these six combinations correspond to six clinical types of sCJD: each type of normal prion produces a particular pathology when it spontaneously deforms to produce sCJD.

But if these proteins deform because of infection with a disease-causing prion, the relationship between pathology and prion type should be different, as it is in vCJD. "If we look at brain samples from sporadic CJD cases and find some that do not fit the pattern," says Kretschmar, "that could mean they were caused by infection."

There are 250 deaths per year from sCJD in the US, and a similar incidence elsewhere. Singeltary and other US activists think that some of these people died after eating contaminated meat or "nutritional" pills containing dried animal brain. Governments will have a hard time facing activists like Singeltary if it turns out that some sCJD isn't as spontaneous as doctors have insisted.

Deslys's work on macaques also provides further proof that the human disease vCJD is caused by BSE. And the experiments showed that vCJD is much more virulent to primates than BSE, even when injected into the bloodstream rather than the brain. This, says Deslys, means that there is an even bigger risk than we thought that vCJD can be passed from one patient to another through contaminated blood transfusions and surgical instruments.

http://www.newscientist.com/article/mg16922840.300-like-lambs-to-the-slaughter.html



Seven main threats for the future linked to prions

The NeuroPrion network has identified seven main threats for the future linked to prions.

First threat

The TSE road map defining the evolution of European policy for protection against prion diseases is based on a certain numbers of hypotheses some of which may turn out to be erroneous. In particular, a form of BSE (called atypical Bovine Spongiform Encephalopathy), recently identified by systematic testing in aged cattle without clinical signs, may be the origin of classical BSE and thus potentially constitute a reservoir, which may be impossible to eradicate if a sporadic origin is confirmed. Also, a link is suspected between atypical BSE and some apparently sporadic cases of Creutzfeldt-Jakob disease in humans. These atypical BSE cases constitute an unforeseen first threat that could sharply modify the European approach to prion diseases.

Second threat

snip...

http://www.neuroprion.org/en/np-neuroprion.html


14th ICID International Scientific Exchange Brochure -

Final Abstract Number: ISE.114

Session: International Scientific Exchange

Transmissible Spongiform encephalopathy (TSE) animal and human TSE in North America

update October 2009

T. Singeltary

Bacliff, TX, USA

Background:

An update on atypical BSE and other TSE in North America. Please remember, the typical U.K. c-BSE, the atypical l-BSE (BASE), and h-BSE have all been documented in North America, along with the typical scrapie's, and atypical Nor-98 Scrapie, and to date, 2 different strains of CWD, and also TME. All these TSE in different species have been rendered and fed to food producing animals for humans and animals in North America (TSE in cats and dogs ?), and that the trading of these TSEs via animals and products via the USA and Canada has been immense over the years, decades.

Methods:

12 years independent research of available data

Results:

I propose that the current diagnostic criteria for human TSEs only enhances and helps the spreading of human TSE from the continued belief of the UKBSEnvCJD only theory in 2009. With all the science to date refuting it, to continue to validate this old myth, will only spread this TSE agent through a multitude of potential routes and sources i.e. consumption, medical i.e., surgical, blood, dental, endoscopy, optical, nutritional supplements, cosmetics etc.

Conclusion:

I would like to submit a review of past CJD surveillance in the USA, and the urgent need to make all human TSE in the USA a reportable disease, in every state, of every age group, and to make this mandatory immediately without further delay. The ramifications of not doing so will only allow this agent to spread further in the medical, dental, surgical arena's. Restricting the reporting of CJD and or any human TSE is NOT scientific. Iatrogenic CJD knows NO age group, TSE knows no boundaries. I propose as with Aguzzi, Asante, Collinge, Caughey, Deslys, Dormont, Gibbs, Gajdusek, Ironside, Manuelidis, Marsh, et al and many more, that the world of TSE Transmissible Spongiform Encephalopathy is far from an exact science, but there is enough proven science to date that this myth should be put to rest once and for all, and that we move forward with a new classification for human and animal TSE that would properly identify the infected species, the source species, and then the route.

http://ww2.isid.org/Downloads/14th_ICID_ISE_Abstracts.pdf


Saturday, March 19, 2011

PRION DISEASE MAN AND ANIMAL SPREADING NORTH AMERICA, WHILE FEDERAL FUNDING TO BE AXED

REQUEST FOR CONTINUING FUNDING FOR THE NATIONAL PRION DISEASE PATHOLOGY SURVEILLANCE CENTER


http://transmissiblespongiformencephalopathy.blogspot.com/2011/03/prion-disease-man-and-animal-spreading.html





Terry S. Singeltary Sr.
P.O. Box 42
Bacliff, Texas USA 77518

Research Project: Transmissible Spongiform Encephalopathies: Identification of atypical scrapie in Canadian sheep

cc:

Editor-in-Chief:

Jeremiah T. Saliki, Athens Diagnostic Laboratory, UGA, Athens, GA 30602 (2009)

Kenneth S. Latimer, Covance Laboratories Inc., Vienna, VA 22182 (2010)

Holly M. Musgrove, Athens Diagnostic Laboratory, UGA, Athens, GA 30602

Kyoung-Jin Yoon (Ames, IA; 2010)




IN REPLY to the following studies published ;




Research Project: Transmissible Spongiform Encephalopathies: the Role of

Genetics, Strain Variation, and Environmental Contamination in Disease Control

Location: Animal Diseases Research

Title: Identification of atypical scrapie in Canadian sheep

Authors

Mitchell, G - Orourke, Katherine Harrington, N - Soutyrine, A - Simmons, M - Dudas, S - Zhuang, Dongyue Laude, H - Balachandran, A -

Submitted to: Canadian Veterinary Journal Publication Type: Peer Reviewed Journal Publication Acceptance Date: December 3, 2009 Publication Date: May 1, 2010 Citation: Mitchell, G.B., Orourke, K.I., Harrington, N.P., Soutyrine, A., Simmons, M.M., Dudas, S., Zhuang, D., Laude, H., Balachandran, A. 2010. Identification of atypical scrapie in Canadian sheep. Canadian Veterinary Journal. 22(3):402-408.

Interpretive Summary: Scrapie is a fatal brain disease of sheep, occurring in most sheep producing areas of the world. The disease occurs as a classical form, infectious within a flock and largely associated with particular forms of the prion gene, and an atypical form, usually found in older animals and often with no clinical signs of disease. There is as yet no evidence for transmission of atypical scrapie Intense eradication efforts in Europe and North America include random testing of clinically normal animals collected at slaughter facilities and testing of sheep dying of unknown causes on farms. The Canadian National Scrapie Surveillance program, through the national and international (Office of International Epizootics) reference laboratory in Ottawa, has identified three cases of atypical scrapie in Canadian sheep. These sheep had genetic, biochemical and histologic profiles similar to those observed in the United States, European, and British cases of Nor98. The finding of atypical scrapie in Canadian sheep was not unexpected and demonstrates the value of the current surveillance program in identifying both classical and atypical scrapie. Coordination of the testing programs in Canada and the U.S. allows both governments to gather comparable data on the nature and extent of Nor98 in sheep flocks in North America and develop harmonized control programs.

Technical Abstract: Scrapie, a transmissible spongiform encephalopathy of sheep and goats, exists in most small ruminant producing countries of the world. An atypical form of this disease, originally termed Nor98, was discovered in large abattoir surveillance of clinically normal, predominantly older sheep and rarely in clinical suspects. Nor98 is presumptively diagnosed by the unconventional findings in enzyme linked immunosorbent and immunohistochemistry assays of the abnormal prion protein in the brain and lymph nodes. Nor98 is usually differentiated from classical scrapie by Western blot analysis and the unique biochemical profile following passage in transgenic mice carrying the ovine prion gene. The Canadian National Scrapie Surveillance Program was initiated in 2005 and involves the active testing of sheep over 12 months of age which are slaughtered at federal and provincial abattoirs, or are identified as fallen stock from rendering companies, sales barns, cull ewe feedlots or farms. This report describes the first three cases of atypical scrapie detected in Canadian sheep. Two of the animals were older than 5 years of age and apparently clinically normal prior to sampling. Two of the sheep carried a polymorphism at codon 141 frequently associated with atypical scrapie and one sheep had a genotype relatively resistant to classical scrapie. Enhanced scrapie surveillance efforts have identified three cases of atypical scrapie in Canada. The classical form of scrapie has been extensively studied, with surveillance and breeding programs currently aimed at reducing disease prevalence. The existence of atypical scrapie in the Canadian sheep flock is not unexpected and additional cases will undoubtedly arise during continued scrapie surveillance efforts. Rapid identification and differentiation of these cases is necessary to understand the national prevalence of atypical scrapie and complement the Canadian initiative to control classical scrapie.


http://www.ars.usda.gov/research/publications/Publications.htm?seq_no_115=245110




Journal of Veterinary Diagnostic Investigation Vol. 22 Issue 3, 408-411 Copyright © 2010 by the American Association of Veterinary Laboratory Diagnosticians This Article

Articles by Mitchell, G. B. Articles by Balachandran, A.

PubMed Citation Articles by Mitchell, G. B. Articles by Balachandran, A.

--------------------------------------------------------------------------------

Brief Research Reports

Identification of atypical scrapie in Canadian sheep


http://jvdi.org/cgi/content/abstract/22/3/408?maxtoshow=&hits=10&RESULTFORMAT=&fulltext=prion&searchid=1&FIRSTINDEX=0&volume=22&issue=3&resourcetype=HWCIT





>>> There is as yet no evidence for transmission of atypical scrapie <<<>. - Sr.Tech.Ed.MJ]


http://www.promedmail.org/pls/otn/f?p=2400:1001:962575216785367::NO::F2400_P1001_BACK_PAGE,F2400_P1001_PUB_MAIL_ID:1000,81729




Research article

The natural atypical scrapie phenotype is preserved on experimental transmission and sub-passage in PRNP homologous sheep

Marion M Simmons1 , Timm Konold1 , Lisa Thurston1 , Susan J Bellworthy1 , Melanie J Chaplin2 and S Jo Moore1

1 Department of Pathology, Veterinary Laboratories Agency Weybridge, New Haw, Addlestone KT15 3NB, UK

2 Molecular Pathogenesis and Genetics Department, Veterinary Laboratories Agency Weybridge, New Haw, Addlestone KT15 3NB, UK

author email corresponding author email

BMC Veterinary Research 2010, 6:14doi:10.1186/1746-6148-6-14

The electronic version of this article is the complete one and can be found online at:


http://www.biomedcentral.com/1746-6148/6/14




Received: 26 October 2009 Accepted: 10 March 2010 Published: 10 March 2010

© 2010 Simmons et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract Background Atypical scrapie was first identified in Norwegian sheep in 1998 and has subsequently been identified in many countries. Retrospective studies have identified cases predating the initial identification of this form of scrapie, and epidemiological studies have indicated that it does not conform to the behaviour of an infectious disease, giving rise to the hypothesis that it represents spontaneous disease.

However, atypical scrapie isolates have been shown to be infectious experimentally, through intracerebral inoculation in transgenic mice and sheep. The first successful challenge of a sheep with 'field' atypical scrapie from an homologous donor sheep was reported in 2007.

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

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


http://www.biomedcentral.com/1746-6148/6/14




PUTTING THE CART BEFORE THE HORSE ;

This position has been accepted by the OIE and the Animal Health Code Article 14.9.1 states “The chapter does not cover so-called ‘atypical’ scrapie which is clinically, pathologically, biochemically and epidemiologically unrelated to ‘classical’ scrapie, may not be contagious and may, in fact, be a spontaneous degenerative condition of older sheep.” This position has been supported by the scientific panel on biological hazards of the European Food Safety Authority 3.

snip...

Recent studies have shown experimental transmission of atypical scrapie in sheep and laboratory animals (Simmons et al 2007) but there is as yet no evidence to confirm that transmission can occur naturally in the field. Another recent paper by Espinosa et al (Espinosa, Herva, 2009) has shown that atypical scrapie can be transmitted with low efficiency to genetically engineered mice over expressing the porcine prion protein. They concluded there was a marked species transmission barrier. Further the agent appeared to undergo a strain phenotype shift upon transmission to the transgenic mice. This is the first report of this occurring.


http://www.biosecurity.govt.nz/files/pests/atypical-scrapie/literature-review.pdf




• Most critical is that atypical scrapie shows higher prevalence in so-called resistant ARR homozygote and heterozygote genotypes, compared with classical scrapie. • Atypical scrapie has not been found naturally in VRQ/VRQ sheep, although such sheep can be infected artificially. VRQ sheep are, in contrast, highly susceptible to classical scrapie. In the UK, one case of atypical scrapie has been found in VRQ heterozygote (AF141RQ/VRQ) sheep. It is important to ascertain whether or not VRQ-carrying sheep are significantly resistant to infection with atypical scrapie or whether the data might result from a failure to detect PrPres in atypical scrapie due to a different pattern of PrP distribution in tissues. • Increased incidence of atypical scrapie in sheep with PrP alleles carrying the variant phenylalanine (F) at position 141 (leucine(L)/phenylalanine) has also been observed compared with classical scrapie. • It will be important to clarify the genotype effect, particularly in relation to ARR and L141F in transmission studies. • In classical scrapie, there is clear evidence for a PrP genotype effect on tissue distribution patterns of PrPres. This might also be true for atypical scrapie although the data are less complete. 4. Transmission of atypical scrapie It has recently18 been demonstrated that atypical scrapie is experimentally transmissible to mice and sheep, primarily through intracerebral injection. There are some data suggesting that it may also be transmissible orally to sheep of different genotypes. The subgroup noted that challenge experiments with atypical scrapie in sheep were underway in the UK, with one successful intracerebral challenge to date. The subgroup was informed that positive transmission of infectivity from atypical scrapie isolated from sheep with a range of genotypes had been observed in mice. This included ovinised transgenic mice overexpressing the VRQ allele. Nor98 atypical scrapie had also transmitted to ARR ovinised mice, with transmission experiments in AF141RQ ovinised mice planned. Biochemical features of the isolates were maintained after transmission, and were distinct from BSE and classical scrapie. High infectivity titres were observed in brain tissue from atypical scrapie, including from ARR/ARR sheep. Brain transmission experiments in mice carrying the human PrP gene were at an early stage. 18 Le Dur A., Béringue V., Andréoletti O., Reine F., Laï T.H., Baron T., Bratberg B., Vilotte J.- L., Sarradin P., Benestad S.L. and Laude H.(2005) A newly identified type of scrapie agent can naturally infect sheep with resistant PrP genotypes. PNAS 102, 16031-16036


http://www.seac.gov.uk/pdf/positionstatement-sheep-subgroup.pdf




A newly identified type of scrapie agent can naturally infect sheep with resistant PrP genotypes

Annick Le Dur*,†, Vincent Béringue*,†, Olivier Andréoletti‡, Fabienne Reine*, Thanh Lan Laï*, Thierry Baron§, Bjørn Bratberg¶, Jean-Luc Vilotte?, Pierre Sarradin**, Sylvie L. Benestad¶, and Hubert Laude*,†† + Author Affiliations

*Virologie Immunologie Moléculaires and ?Génétique Biochimique et Cytogénétique, Institut National de la Recherche Agronomique, 78350 Jouy-en-Josas, France; ‡Unité Mixte de Recherche, Institut National de la Recherche Agronomique-Ecole Nationale Vétérinaire de Toulouse, Interactions Hôte Agent Pathogène, 31066 Toulouse, France; §Agence Française de Sécurité Sanitaire des Aliments, Unité Agents Transmissibles Non Conventionnels, 69364 Lyon, France; **Pathologie Infectieuse et Immunologie, Institut National de la Recherche Agronomique, 37380 Nouzilly, France; and ¶Department of Pathology, National Veterinary Institute, 0033 Oslo, Norway Edited by Stanley B. Prusiner, University of California, San Francisco, CA (received for review March 21, 2005)

Next Section Abstract Scrapie in small ruminants belongs to transmissible spongiform encephalopathies (TSEs), or prion diseases, a family of fatal neurodegenerative disorders that affect humans and animals and can transmit within and between species by ingestion or inoculation. Conversion of the host-encoded prion protein (PrP), normal cellular PrP (PrPc), into a misfolded form, abnormal PrP (PrPSc), plays a key role in TSE transmission and pathogenesis. The intensified surveillance of scrapie in the European Union, together with the improvement of PrPSc detection techniques, has led to the discovery of a growing number of so-called atypical scrapie cases. These include clinical Nor98 cases first identified in Norwegian sheep on the basis of unusual pathological and PrPSc molecular features and “cases” that produced discordant responses in the rapid tests currently applied to the large-scale random screening of slaughtered or fallen animals. Worryingly, a substantial proportion of such cases involved sheep with PrP genotypes known until now to confer natural resistance to conventional scrapie. Here we report that both Nor98 and discordant cases, including three sheep homozygous for the resistant PrPARR allele (A136R154R171), efficiently transmitted the disease to transgenic mice expressing ovine PrP, and that they shared unique biological and biochemical features upon propagation in mice. These observations support the view that a truly infectious TSE agent, unrecognized until recently, infects sheep and goat flocks and may have important implications in terms of scrapie control and public health.

SNIP...

Our study demonstrates that an authentic TSE infectious agent is responsible in sheep and goats of sporadic atypical infections that remained unnoticed until recently. This raises important issues with regard to control of scrapie infection in small ruminants. Of major concern, ARR/ARR sheep can no longer be regarded as free of natural TSE infection. This finding challenges, at least to some extent, the foundation of the selective breeding programs engaged in several European Union member states (47, 48) and may call for a reappraisal of possible consequences of this strategy in the long term. Finally, more information about this newly discovered type of TSE agent, its prevalence in countries free of scrapie or BSE disease, and its potential to across-species transmission would be needed for a comprehensive evaluation of its implications in terms of public health.


http://www.pnas.org/content/102/44/16031.long



http://www.pnas.org/content/102/44/16031.figures-only




SNIP...

SEE FULL TEXT ;

Monday, November 23, 2009

A case of atypical scrapie/Nor98 in a sheep from New Zealand


http://nor-98.blogspot.com/2009/11/case-of-atypical-scrapienor98-in-sheep.html




If the scrapie agent is generated from ovine DNA and thence causes disease in other species, then perhaps, bearing in mind the possible role of scrapie in CJD of humans (Davinpour et al, 1985), scrapie and not BSE should be the notifiable disease. ...


http://collections.europarchive.org/tna/20090505194948/http://bseinquiry.gov.uk/files/yb/1988/06/08004001.pdf




1: J Infect Dis 1980 Aug;142(2):205-8

Oral transmission of kuru, Creutzfeldt-Jakob disease, and scrapie to nonhuman primates.

Gibbs CJ Jr, Amyx HL, Bacote A, Masters CL, Gajdusek DC.

Kuru and Creutzfeldt-Jakob disease of humans and scrapie disease of sheep and goats were transmitted to squirrel monkeys (Saimiri sciureus) that were exposed to the infectious agents only by their nonforced consumption of known infectious tissues. The asymptomatic incubation period in the one monkey exposed to the virus of kuru was 36 months; that in the two monkeys exposed to the virus of Creutzfeldt-Jakob disease was 23 and 27 months, respectively; and that in the two monkeys exposed to the virus of scrapie was 25 and 32 months, respectively. Careful physical examination of the buccal cavities of all of the monkeys failed to reveal signs or oral lesions. One additional monkey similarly exposed to kuru has remained asymptomatic during the 39 months that it has been under observation.

snip...

The successful transmission of kuru, Creutzfeldt-Jakob disease, and scrapie by natural feeding to squirrel monkeys that we have reported provides further grounds for concern that scrapie-infected meat may occasionally give rise in humans to Creutzfeldt-Jakob disease.

PMID: 6997404


http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6997404&dopt=Abstract




Recently the question has again been brought up as to whether scrapie is transmissible to man. This has followed reports that the disease has been transmitted to primates. One particularly lurid speculation (Gajdusek 1977) conjectures that the agents of scrapie, kuru, Creutzfeldt-Jakob disease and transmissible encephalopathy of mink are varieties of a single "virus". The U.S. Department of Agriculture concluded that it could "no longer justify or permit scrapie-blood line and scrapie-exposed sheep and goats to be processed for human or animal food at slaughter or rendering plants" (ARC 84/77)" The problem is emphasised by the finding that some strains of scrapie produce lesions identical to the once which characterise the human dementias"

Whether true or not. the hypothesis that these agents might be transmissible to man raises two considerations. First, the safety of laboratory personnel requires prompt attention. Second, action such as the "scorched meat" policy of USDA makes the solution of the acrapie problem urgent if the sheep industry is not to suffer grievously.

snip...

76/10.12/4.6


http://web.archive.org/web/20010305223125/www.bseinquiry.gov.uk/files/yb/1976/10/12004001.pdf




snip...

please see full text ;

Sunday, April 18, 2010

SCRAPIE AND ATYPICAL SCRAPIE TRANSMISSION STUDIES A REVIEW 2010


http://scrapie-usa.blogspot.com/2010/04/scrapie-and-atypical-scrapie.html




Sunday, March 28, 2010

Nor-98 atypical Scrapie, atypical BSE, spontaneous TSE, trade policy, sound science ?


http://nor-98.blogspot.com/2010/03/nor-98-atypical-scrapie-atypical-bse.html




position: Post Doctoral Fellow Atypical BSE in Cattle

Closing date: December 24, 2009

Anticipated start date: January/February 2010

Employer: Canadian and OIE Reference Laboratories for BSE CFIA Lethbridge Laboratory, Lethbridge/Alberta

The Canadian and OIE reference laboratories for BSE are extensively involved in prion diseases diagnosis and research. With a recent increase in research activities and funding, the laboratory is looking to fill two post doctoral fellow positions. Both positions will be located at the Canadian Food Inspection Agency (CFIA) Lethbridge Laboratory which offers biosaftey level 3 (BSL3) and BSL2 laboratory space and is well equipped for molecular and morphologic prion research. The facility also has a BSL3 large animal housing wing and a state of the art post mortem room certified for prion work. Successful candidates will have the opportunity to visit other laboratories to cooperate in various aspects of the projects and to be trained in new techniques and acquire new skills. With a recent increase in prion disease expertise and research in Alberta and Canada, these positions will offer significant exposure to cutting edge prion science via videoconferencing, meetings, workshops and conferences. These interactions will also provide a valuable opportunity to present research findings and discuss potential future work opportunities and collaborations with other Canadian and international research groups.

Atypical BSE in Cattle

BSE has been linked to the human disease variant Creutzfeldt Jakob Disease (vCJD). The known exposure pathways for humans contracting vCJD are through the consumption of beef and beef products contaminated by the BSE agent and through blood transfusions. However, recent scientific evidence suggests that the BSE agent may play a role in the development of other forms of human prion diseases as well. These studies suggest that classical type of BSE may cause type 2 sporadic CJD and that H-type atypical BSE is connected with a familial form of CJD.

To date the OIE/WAHO assumes that the human and animal health standards set out in the BSE chapter for classical BSE (C-Type) applies to all forms of BSE which include the H-type and L-type atypical forms. This assumption is scientifically not completely justified and accumulating evidence suggests that this may in fact not be the case. Molecular characterization and the spatial distribution pattern of histopathologic lesions and immunohistochemistry (IHC) signals are used to identify and characterize atypical BSE. Both the L-type and H-type atypical cases display significant differences in the conformation and spatial accumulation of the disease associated prion protein (PrPSc) in brains of afflicted cattle. Transmission studies in bovine transgenic and wild type mouse models support that the atypical BSE types might be unique strains because they have different incubation times and lesion profiles when compared to C-type BSE. When L-type BSE was inoculated into ovine transgenic mice and Syrian hamster the resulting molecular fingerprint had changed, either in the first or a subsequent passage, from L-type into C-type BSE. In addition, non-human primates are specifically susceptible for atypical BSE as demonstrated by an approximately 50% shortened incubation time for L-type BSE as compared to C-type. Considering the current scientific information available, it cannot be assumed that these different BSE types pose the same human health risks as C-type BSE or that these risks are mitigated by the same protective measures.

This study will contribute to a correct definition of specified risk material (SRM) in atypical BSE. The incumbent of this position will develop new and transfer existing, ultra-sensitive methods for the detection of atypical BSE in tissue of experimentally infected cattle.

Responsibilities include:

Driving research at the National and OIE BSE reference lab to ensure project milestones are met successfully. Contributing to the preparation of project progress reports. Directing technical staff working on the project. Communicating and discussing results, progress and future direction with project principle investigator(s). Communicating with collaborative project partners. Qualifications:

Successful completion of a PhD degree in an area focusing on or related to prion diseases. Extensive experience with molecular and/or morphologic techniques used in studying prion diseases and/or other protein misfolding disorders. Ability to think independently and contribute new ideas. Excellent written and oral communication skills. Ability to multitask, prioritize, and meet challenges in a timely manner. Proficiency with Microsoft Office, especially Word, PowerPoint and Excel. How to apply:

Please send your application and/or inquiry to: Dr. Stefanie Czub, DVM, Ph.D. Head, National and OIE BSE Reference Laboratory Canadian Food Inspection Agency Lethbridge Laboratory P.O. Box 640, Township Road 9-1 Lethbridge, AB, T1J 3Z4 Canada

phone: +1-403-382-5500 +1-403-382-5500 ext. 5549 email:

stefanie.czub@inspection.gc.ca

Contact Info:


http://www.prionetcanada.ca/detail.aspx?menu=5&dt=293380&app=93&cat1=387&tp=20&lk=no&cat2




P26 TRANSMISSION OF ATYPICAL BOVINE SPONGIFORM ENCEPHALOPATHY (BSE) IN HUMANIZED MOUSE MODELS

Liuting Qing1, Fusong Chen1, Michael Payne1, Wenquan Zou1, Cristina Casalone2, Martin Groschup3, Miroslaw Polak4, Maria Caramelli2, Pierluigi Gambetti1, Juergen Richt5*, and Qingzhong Kong1 1Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA; 2CEA, Istituto Zooprofilattico Sperimentale, Italy; 3Friedrich-Loeffler-Institut, Germany; 4National Veterinary Research Institute, Poland; 5Kansas State University, Diagnostic Medicine/Pathobiology Department, Manhattan, KS 66506, USA. *Previous address: USDA National Animal Disease Center, Ames, IA 50010, USA

Classical BSE is a world-wide prion disease in cattle, and the classical BSE strain (BSE-C) has led to over 200 cases of clinical human infection (variant CJD). Two atypical BSE strains, BSE-L (also named BASE) and BSE-H, have been discovered in three continents since 2004. The first case of naturally occurring BSE with mutated bovine PrP gene (termed BSE-M) was also found in 2006 in the USA. The transmissibility and phenotypes of these atypical BSE strains/isolates in humans were unknown. We have inoculated humanized transgenic mice with classical and atypical BSE strains (BSE-C, BSE-L, BSE-H) and the BSE-M isolate. We have found that the atypical BSE-L strain is much more virulent than the classical BSE-C. The atypical BSE-H strain is also transmissible in the humanized transgenic mice with distinct phenotype, but no transmission has been observed for the BSE-M isolate so far.

III International Symposium on THE NEW PRION BIOLOGY: BASIC SCIENCE, DIAGNOSIS AND THERAPY 2 - 4 APRIL 2009, VENEZIA (ITALY)


http://www.istitutoveneto.it/prion_09/Abstracts_09.pdf




Monday, November 23, 2009

BSE GBR RISK ASSESSMENTS UPDATE NOVEMBER 23, 2009 COMMISSION OF THE EUROPEAN COMMUNITIES AND O.I.E.


http://docket-aphis-2006-0041.blogspot.com/2009/11/bse-gbr-risk-assessments-update.html




Wednesday, February 10, 2010

NAIS MAD COW TRACEABILITY DUMPED BY USDA APHIS 2010


http://naiscoolyes.blogspot.com/2010/02/nais-mad-cow-traceability-dumped-by.html




IN A NUT SHELL ;

(Adopted by the International Committee of the OIE on 23 May 2006)

11. Information published by the OIE is derived from appropriate declarations made by the official Veterinary Services of Member Countries. The OIE is not responsible for inaccurate publication of country disease status based on inaccurate information or changes in epidemiological status or other significant events that were not promptly reported to the Central Bureau,


http://www.oie.int/eng/Session2007/RF2006.pdf




Wednesday, May 19, 2010

Molecular, Biochemical and Genetic Characteristics of BSE in Canada


http://bse-atypical.blogspot.com/2010/05/molecular-biochemical-and-genetic.html




THE OIE has now shown they are nothing more than a National Trading Brokerage for all strains of animal TSE. AS i said before, OIE should hang up there jock strap now, since it appears they will buckle every time a country makes some political hay about trade protocol, commodities and futures. IF they are not going to be science based, they should do everyone a favor and dissolve there organization.

...snip

IT'S as obvious as day and night, either Larry, Curley, and Mo have been at the helm of the USDA/APHIS/FSIS/FDA/CDC/NIH et al for many many years, or the incompetence of these agencies are so inept, either through ignorance and or just too overweight with industry reps., they then should be all done away with and a single agency brought forth, and if not, how will you correct this ongoing problem ?

Thank you, I am sincerely disgusted,

Terry S. Singeltary Sr. P.O. Box 42 Bacliff, Texas USA 77518

...snip

full text ;

Sunday, February 14, 2010

[Docket No. FSIS-2006-0011] FSIS Harvard Risk Assessment of Bovine Spongiform Encephalopathy (BSE)


http://bseusa.blogspot.com/2010/02/docket-no-fsis-2006-0011-fsis-harvard.html




PLEASE SEE FULL TEXT 98 PAGES HERE ;


http://www.fsis.usda.gov/OPPDE/Comments/2006-0011/2006-0011-1.pdf




COMMONWEALTH OF AUSTRALIA

Proof Committee Hansard


http://docket-aphis-2006-0041.blogspot.com/2010/03/commonwealth-of-australia-hansard.html




Wednesday, February 24, 2010

Transmissible Spongiform encephalopathy (TSE) animal and human TSE in North America 14th

ICID International Scientific Exchange Brochure -


http://transmissiblespongiformencephalopathy.blogspot.com/2010/02/transmissible-spongiform-encephalopathy.html




http://transmissiblespongiformencephalopathy.blogspot.com/




England worried briefly about infecting other countries


http://www.mad-cow.org/00/aug00_last_news.html#fff





spontaneous TSE, fact or fiction $$$




Agriculture & Natural Resources Research & Extension Centers Sierra Foothill Research & Extension Center (University of California, Davis) Year 2004 Paper bse prevention update BSE Prevention Update: Comparing France and California John Maas School of Veterinary Medicine, UC Davis


Does BSE occur spontaneously in cattle? The message that BSE occurs spontaneously in cattle has been repeated in the media several times. Where does this idea come from? There is a disease in humans called Creutzfeldt-Jakob Disease (CJD) which does occur spontaneously. It occurs at a rate of about 1-2 people per million population per year, worldwide. This is the so-called spontaneous CJD. Some have extrapolated this information to the cattle population, saying that BSE occurs spontaneously in cattle just as spontaneous CJD occurs in humans. Therefore, if we have about 100 million cattle in the U.S., we have 100-200 cases of BSE each year. This assumption is the basis for the argument that we should be testing every slaughtered animal for BSE. There is no basis in fact for this assumption, however. To the contrary, there is ample evidence that BSE is not occurring spontaneously. For example, we have been able to detect cattle diseases with public health significance that occurs at a much lower rate than 1 per million and one such disease is rabies. The diagnosis of rabies is dependent on a thorough examination of the brain of the animal. BSE diagnosis is also dependent on the complete examination and testing of the animal’s brain. In California, cattle rabies is detected every year or so and almost every case is associated with significant human exposure. If we were unable to detect this central nervous system disease (rabies) one or more fatal cases of rabies in humans would occur. The fact is, we are able to routinely diagnose rabies and the same experts are more than capable of diagnosing BSE. Every veterinary diagnostic laboratory in every state is actively looking for BSE and has been since 1986. We are not missing the diagnosis of BSE in cattle in the U.S. Those who are publicly concerned about spontaneous BSE in cattle and who advocate testing all slaughtered cattle are not at all concerned about beef products imported into the U.S. If BSE does spontaneously occur, it must do so world wide, thus imported beef products would carry the same or greater risk. We must insist on using the science as our guide in making policy regarding BSE.

SNIP...



http://escholarship.org/uc/item/7kw4m8d5





Science 24 September 2004: Vol. 305. no. 5692, pp. 1918 - 1921 DOI: 10.1126/science.1103581

Perspectives BIOMEDICINE:

A Fresh Look at BSE

Bruce Chesebro*

snip...

BSE caused by spontaneous misfolding of the prion protein has not been proven.

snip...

What can we conclude so far about BSE in North America? Is the BSE detected in two North American cows sporadic or spontaneous or both? "Sporadic" pertains to the rarity of disease occurrence. "Spontaneous" pertains to a possible mechanism of origin of the disease. These are not equivalent terms. The rarity of BSE in North America qualifies it as a sporadic disease, but this low incidence does not provide information about cause. For the two reported North American BSE cases, exposure to contaminated MBM remains the most likely culprit. However, other mechanisms are still possible, including cross-infection by sheep with scrapie or cervids with CWD, horizontal transmission from cattle with endemic BSE, and spontaneous disease in individual cattle. Based on our understanding of other TSEs, the spontaneous mechanism is probably the least likely. Thus, "idiopathic" BSE--that is, BSE of unknown etiology--might be a better term to describe the origin of this malady.

snip...

References

S. B. Prusiner, Proc. Natl. Acad. Sci. U.S.A 95, 13363 (1998) [Medline]. P. G. Smith, R. Bradley, Br. Med. Bull. 66, 185 (2003) [Medline]. C. Weissmann, A. Aguzzi, Curr. Opin. Neurobiol. 7, 695 (1997) [Medline]. A. F. Hill et al., J. Gen. Virol. 80, 11 (1999) [Medline]. R. Chiesa et al., J. Virol. 77, 7611 (2003) [Medline]. G. Legname et al., Science 305, 673 (2004). D. Westaway et al., Cell 76, 117 (1994) [Medline]. B. Chesebro, Science 279, 42 (1998). A. G. Biacabe et al., EMBO Rep. 5, 110 (2004) [Medline]. Y. Yamakawa et al., Jpn. J. Infect. Dis. 56, 221 (2003) [Medline]. C. Casalone et al., Proc. Natl. Acad. Sci. U.S.A. 101, 3065 (2004) [Medline]. E. F. Houston et al., J. Gen. Virol. 83, 1247 (2002) [Medline].

Laboratory of Persistent Viral Diseases Bruce W. Chesebro, M.D., Chief The Laboratory of Persistent Viral Diseases (LPVD) is concerned with studies of persistent active or latent viral or prion disease infections. Investigators place particular emphasis on persistent infections of the nervous system and of the hemopoietic and lymphoid systems. The laboratory is also studying the roles of persistent infection in the development of retrovirus-induced immunosuppression. Models being examined include prion diseases of various species, murine and human retroviruses, and tick-borne encephalitis viruses.


http://www.sciencemag.org/cgi/content/full/305/5692/1918




Genetic mutation, genetic predisposition and sporadic BSE Theoretically, it is possible that BARBs cases result not from “infection” but rather from sporadic genetic mutations (“sporadic BSE”) or genetic predisposition to infection. Wilesmith et al (2003) suggest that the incidence of BARBs is too high to be compatible with a genetic mutation. The difference in incidence between dairy animals and animals reared in beef suckler herds is not consistent with a genetically based origin as all breeds appear to be susceptible to BSE. Also many countries with higher cattle populations have not reported BSE cases and in addition, the observation of (two sets of) two BARB cases in the same herd presents a strong argument against spontaneous mutation, at least for these cases.


http://www.seac.gov.uk/papers/seac80_4.pdf




US beef industry leaders say scientists should not speculate about the unusual case.

"There's no evidence that it's atypical ... and there's absolutely no evidence that it's spontaneous," said Gary Weber, head of regulatory affairs at the National Cattlemen's Beef Association.


http://www.agobservatory.org/headlines.cfm?refID=73207




Prions: Protein Aggregation and Infectious Diseases ADRIANO AGUZZI AND ANNA MARIA CALELLA Institute of Neuropathology, University Hospital of Zurich, Zurich, Switzerland

3. Sporadic Creutzfeldt-Jakob disease Approximately 85% of all human prion diseases are sporadic forms of CJD. For sCJD, there is no association with a mutant PRNP allele, nor is there any epidemiological evidence for exposure to a TSE agent through contact with people or animals infected with TSEs. sCJD cases are currently subclassified according to the methionine/valine polymorphism at codon 129 of the PRNP gene and the size and glycoform ratio of proteaseresistant prion protein identified on western blot (type 1 or type 2) (174). Heterozygosity (Met/Val) at PrP codon 129 appears to be associated with a lower risk (378) and/or prolonged incubation time (119, 387). The lack of routine laboratory testing for preclinical diagnosis makes the search for agent sources and other risk factors extremely difficult. At present, the means of acquisition of a TSE agent in these patients remains a mystery. So far, there is no evidence for spontaneous PrPSc formation in any animal or human TSE. In humans, the peak age incidence of sporadic CJD is 55–60 years. However, if spontaneous misfolding were the primary event, one might expect a continuously increasing incidence with age because more time would allow more opportunity for rare misfolding events.

Physiol Rev • VOL 89 • OCTOBER 2009 • http://www.prv.org/




Wednesday, March 3, 2010

NOR-98 ATYPICAL SCRAPIE USA 4 CASES DETECTED JANUARY 2010


http://nor-98.blogspot.com/2010/03/nor-98-atypical-scrapie-usa-4-cases.html



SNIP...END...TSS




2ND UPDATE JUNE 16, 2009




----- Original Message -----
From: Terry S. Singeltary Sr.
To: BSE-L@LISTS.AEGEE.ORG
Sent: Wednesday, June 16, 2010 11:23 AM
Subject: Re: [BSE-L] Research Project: Transmissible Spongiform Encephalopathies: Identification of atypical scrapie in Canadian sheep


Greetings again Dr. Saliki et al,


Thank you for your kind reply.


Dr. Saliki states ;



"Your main concern appears to be te statement "There is as yet no evidence for transmission of atypical scrapie". However, a closer look at the article we published in the Journal of Veterinary Diagnostic Investigation (JVDI) found no such sentence in the article. On the contrary, the authors [appropriately] discussed in the second paragraph of page 411 the question of transmissibility of atypical scrapie. If the sentence that troubles you was published somewhere, the JVDI has no responsibility or accountability for that."


end...TSS



Greetings again Dr. Saliki et al,


This is very disturbing to me.


IF you see the article published on the ARS research site referencing the same study at JVDI, it plainly states ;


Submitted to: Canadian Veterinary Journal Publication

Type: Peer Reviewed Journal

Publication Acceptance Date: December 3, 2009 Publication Date: May 1, 2010

Citation: Mitchell, G.B., Orourke, K.I., Harrington, N.P., Soutyrine, A., Simmons, M.M., Dudas, S., Zhuang, D., Laude, H., Balachandran, A. 2010.


Identification of atypical scrapie in Canadian sheep.

Canadian Veterinary Journal. 22(3):402-408.


Interpretive Summary:


> There is as yet no evidence for transmission of atypical scrapie



http://www.ars.usda.gov/research/publications/Publications.htm?seq_no_115=245110





THIS is the exact same study below, with the exact same authors ;




Journal of Veterinary Diagnostic Investigation Vol. 22 Issue 3, 408-411
Copyright © 2010 by the American Association of Veterinary Laboratory Diagnosticians
Articles by Mitchell, G. B. Articles by Balachandran, A.



Brief Research Reports

Identification of atypical scrapie in Canadian sheep

Gordon B. Mitchell, Katherine I. O'Rourke, Noel P. Harrington, Andrei Soutyrine, Marion M. Simmons, Sandor Dudas, Dongyue Zhuang, Hubert Laude and Aru Balachandran1, Correspondence: 1Corresponding Author: Aru Balachandran, Canadian Food Inspection Agency, Ottawa Laboratory–Fallowfield, 3851 Fallowfield Road, Ottawa, Ontario, Canada, K2H 8P9. Aru.Balachandran@inspection.gc.ca



Reports

Identification of atypical scrapie in Canadian sheep Gordon B. Mitchell, Katherine I. O'Rourke, Noel P. Harrington, Andrei Soutyrine, Marion M. Simmons, Sandor Dudas, Dongyue Zhuang, Hubert Laude and Aru Balachandran1, Correspondence: 1Corresponding Author: Aru Balachandran, Canadian Food Inspection Agency, Ottawa Laboratory–Fallowfield, 3851 Fallowfield Road, Ottawa, Ontario, Canada, K2H 8P9. Aru.Balachandran@inspection.gc.ca

Scrapie, a transmissible spongiform encephalopathy of sheep and goats, exists in most small ruminant-producing countries of the world. A novel form of this disease was recently recognized and is known by various names, including Nor98, Nor98-like, and atypical scrapie. Differing from classic scrapie in epidemiology, histopathology, and biochemical characteristics, atypical scrapie cases have been identified throughout Europe and in the United States. Enhanced scrapie surveillance efforts recently identified 3 cases of atypical scrapie in Canada.

Key Words: Atypical • Nor98 • prion • scrapie • sheep • transmissible spongiform encephalopathy



http://jvdi.org/cgi/content/abstract/22/3/408?maxtoshow=&hits=10&RESULTFORMAT=&fulltext=prion&searchid=1&FIRSTINDEX=0&volume=22&issue=3&resourcetype=HWCIT




BUT yet, in the same study that was published by JVDI, with the same authors (references above), it does not state this, and I was aware of this in the short abstract, but I _assumed_ that the ARS research was not capable of changing what a peer review journal study said, and apparently I was wrong about that. One would think (hope), one would have thought, that the ARS was not capable of changing what the study said or it's interpretation there from, and that is exactly what happened. IT now seems that this sentence was added to this study by the ARS research on the ARS page referencing the exact same study in JVDI.




> There is as yet no evidence for transmission of atypical scrapie



THIS is the only interpretation of this 'incomprehensible' TSE prion mess I can understand as a lay person. From day one politics have trumped science, and science has been changed to fit the political agenda, as was proven again here with this study "Research Project: Transmissible Spongiform Encephalopathies: Identification of atypical scrapie in Canadian sheep." Scientific findings were manipulated once again, as they have been in the past with other scientific findings and research papers. The Governments around the globe do not want, cannot have, Scrapie of any kind transmitting to anything, especially the atypical Scrapie, because they have already decided and made legal, without any scientific evidence, atypical Scrapie should not, cannot, and by God will not transmit to livestock or humans. IN fact they were so sure, they changed the OIE TSE guidelines, and made atypical Scrapie a legal trading commodity, before any scientific transmission studies said it was o.k. IN fact, if someone would just look at transmission studies to date on typical and atypical scrapie, there is more scientific evidence showing that indeed these TSE will transmit to different species, including man. SO, I can see why the ARS research et al would add something like the following statement to your study, their life, and many others depend on it.


IN fact, you can see where this sentence was added into this ARS research paper referencing your study, because there was no (period) where the sentence ended, and where the period was suppose to be, the next sentence starts "Intense eradication efforts" with a capital letter. SO, you can see the following sentence was a late add on ;



> There is as yet no evidence for transmission of atypical scrapie



and the science of Transmissible Spongiform Encephalopathy was once again a culprit of manipulation, fraud, and fabrication.




Dr. Saliki states that ;



> If the sentence that troubles you was published somewhere, the JVDI has no responsibility or accountability for that."



I kindly disagree Sir. THE way the ARS research interpretation and reference of this study in JVDI was referenced with the added sentence that was not part of the study on the ARS site ;



> There is as yet no evidence for transmission of atypical scrapie



LED me to believe that the above statement was in the full text pdf of the original study at JVDI, and I personally believe that JVDI was well aware of it. I could be wrong on that. I will have to take you word on it.


HOWEVER, now that this has been brought to your attention, whether or not JVDI knew about it or not, I think it JVDI's and you Sir, I think it your duty to call ARS on this, and have the sentence "There is as yet no evidence for transmission of atypical scrapie" _removed_ from the ARS research paper referencing JVDI study on Identification of atypical scrapie in Canadian sheep, with a reference of correction and explaination as how this happened by ARS research.


IF not, this should bring into serious question the credibility of JVDI as a peer review journal, and to the ARS research team and all their scientific work.


please see ARS research and reference in question to this study at JVDI ;




Research Project: Transmissible Spongiform Encephalopathies: the Role of Genetics, Strain Variation, and Environmental Contamination in Disease Control Location: Animal Diseases Research

Title: Identification of atypical scrapie in Canadian sheep

Authors

Mitchell, G - Orourke, Katherine Harrington, N - Soutyrine, A - Simmons, M - Dudas, S - Zhuang, Dongyue Laude, H - Balachandran, A -

Submitted to: Canadian Veterinary Journal Publication Type: Peer Reviewed Journal Publication Acceptance Date: December 3, 2009 Publication Date: May 1, 2010 Citation: Mitchell, G.B., Orourke, K.I., Harrington, N.P., Soutyrine, A., Simmons, M.M., Dudas, S., Zhuang, D., Laude, H., Balachandran, A. 2010. Identification of atypical scrapie in Canadian sheep. Canadian Veterinary Journal. 22(3):402-408.

Interpretive Summary: Scrapie is a fatal brain disease of sheep, occurring in most sheep producing areas of the world. The disease occurs as a classical form, infectious within a flock and largely associated with particular forms of the prion gene, and an atypical form, usually found in older animals and often with no clinical signs of disease. There is as yet no evidence for transmission of atypical scrapie Intense eradication efforts in Europe and North America include random testing of clinically normal animals collected at slaughter facilities and testing of sheep dying of unknown causes on farms. The Canadian National Scrapie Surveillance program, through the national and international (Office of International Epizootics) reference laboratory in Ottawa, has identified three cases of atypical scrapie in Canadian sheep. These sheep had genetic, biochemical and histologic profiles similar to those observed in the United States, European, and British cases of Nor98. The finding of atypical scrapie in Canadian sheep was not unexpected and demonstrates the value of the current surveillance program in identifying both classical and atypical scrapie. Coordination of the testing programs in Canada and the U.S. allows both governments to gather comparable data on the nature and extent of Nor98 in sheep flocks in North America and develop harmonized control programs.


Technical Abstract: Scrapie, a transmissible spongiform encephalopathy of sheep and goats, exists in most small ruminant producing countries of the world. An atypical form of this disease, originally termed Nor98, was discovered in large abattoir surveillance of clinically normal, predominantly older sheep and rarely in clinical suspects. Nor98 is presumptively diagnosed by the unconventional findings in enzyme linked immunosorbent and immunohistochemistry assays of the abnormal prion protein in the brain and lymph nodes. Nor98 is usually differentiated from classical scrapie by Western blot analysis and the unique biochemical profile following passage in transgenic mice carrying the ovine prion gene. The Canadian National Scrapie Surveillance Program was initiated in 2005 and involves the active testing of sheep over 12 months of age which are slaughtered at federal and provincial abattoirs, or are identified as fallen stock from rendering companies, sales barns, cull ewe feedlots or farms. This report describes the first three cases of atypical scrapie detected in Canadian sheep. Two of the animals were older than 5 years of age and apparently clinically normal prior to sampling. Two of the sheep carried a polymorphism at codon 141 frequently associated with atypical scrapie and one sheep had a genotype relatively resistant to classical scrapie. Enhanced scrapie surveillance efforts have identified three cases of atypical scrapie in Canada. The classical form of scrapie has been extensively studied, with surveillance and breeding programs currently aimed at reducing disease prevalence. The existence of atypical scrapie in the Canadian sheep flock is not unexpected and additional cases will undoubtedly arise during continued scrapie surveillance efforts. Rapid identification and differentiation of these cases is necessary to understand the national prevalence of atypical scrapie and complement the Canadian initiative to control classical scrapie.

Project Team

Orourke, Katherine Knowles, Donald - Don White, Stephen Schneider, David

Publications

Publications

Related National Programs

Animal Health (103)

Related Projects

Development of Sensitive in Vitro Techniques for Prion Detection Transgenic Analysis of Chronic Wasting Disease Strains Strain Typing of Chronic Wasting Disease (Cwd) and Scrapie by Intracerebral Inoculation into Transgenic and Inbred Mouse Lines Dissemination of Abnormal Prion Protein in the Neural and Extraneural Tissues of Wild Rocky Mountain Elk

Last Modified: 06/15/2010



http://www.ars.usda.gov/research/publications/Publications.htm?seq_no_115=245110





Something should be corrected somewhere, by someone, because the statement "There is as yet no evidence for transmission of atypical scrapie" is not correct. ...



Thank You,
With Kindest Regards,

I am sincerely,

Terry S. Singeltary Sr.
P.O. Box 42
Bacliff, Texas USA 77518
flounder9@verizon.net




P.S. a look how TSE science and research have been manipulated in the past ;



BSE SCIENTIST WAS 'CENSORED'

He says that when he worked at MAFF, ''the way it was structurally set up was not that science would drive the politics, but that the politics will drive the science. And that's wrong.''

http://web.archive.org/web/20030526121511/http://www.bseinquiry.gov.uk/files/yb/1997/12/11001001.pdf



Richard Horton Waffles on Lancet's Wakefield Retraction

Sally Beck Posted: February 12, 2010 03:00 PM

The Lancet has officially retracted a study which sparked a health scare over the MMR vaccine. The leading British medical journal said that it accepts that claims made by Dr. Andrew Wakefield and two fellow researchers were 'false.'

SNIP...

The paper was peer reviewed and duly published back in early 1998. The researchers included a line stating that eight of the parents felt the MMR vaccine had played a part in their children's decline. Horton knew this was controversial but published anyway. He said: "We felt it was important not to censor the information. We had censored information regarding BSE (Bovine spongiform encephalopathy, known as mad cow disease) and CJD (Creutzfeldt-Jakob disease, the human form of BSE). We knew there was a risk that BSE could be transferred from cows to humans, but at the time we thought the risk was small so we didn't include the information. It was a big mistake and we should have published it."

http://www.huffingtonpost.com/sally-beck/richard-horton-waffles-on_b_460550.html



8. I was in receipt of no extra funds beyond those provided by the NHS and the University of London to run my laboratories and pay my salary as a senior lecturer/honorary Consultant and I suffered no constraints over my publications, lectures to my students, or statements to the media. However, I became increasingly aware after 1988 that questioning official dogma about BSE brought difficulties to one’s career. I was myself about to retire from the Charing Cross Hospital, where I worked as a Consultant Neuropathologist, but I observed with horror that the good reputations of dissenting scientists in the field, not least Dr Stephen Dealler and especially Dr Harash Narang were systematically undermined.

http://collections.europarchive.org/tna/20080102135133/http://www.bseinquiry.gov.uk/files/ws/s410.pdf



THEY KNEW 2 DECADES AGO the damn BSE mad cow testing were not finding cases ;

BSE-NON-CONFIRMATION OF DISEASE

3. A question posed by Mr Whaley (para 2) is that classical lesions of BSE may not occur in all cases. Supposing we had a strain variant that produced it's lesions in the cerebrum these would not be detected by our current method. I think this would be unlikely but not impossible - another reason why at least a proportion of complete brains (or blocks) should be retained during the epidemic so if the problem Mr Whaley indicates escalates, it can be investigated.

snip...

5. IF you had the information what benefit would there be ? what would you do with it ?

CONCLUSION

I do not recommend any action. The situation should be accepted. I do not think the VIS can do more at present. The situation should be kept under review particularly if there is an escalation in numbers in this category.

R BRADLEY

15 MAY 1990

90/5.15/3.2


http://collections.europarchive.org/tna/20090505194948/http://bseinquiry.gov.uk/files/yb/1990/05/15003001.pdf



http://collections.europarchive.org/tna/20090505194948/http://bseinquiry.gov.uk/files/yb/1990/05/15003001.pdf



Tuesday, November 17, 2009

SEAC NEW RESULTS ON IDIOPATHIC BRAINSTEM NEURONAL CHROMATOLYSIS (IBNC) FROM THE VETERINARY LABORATORIES AGENCY (VLA) SEAC 103/1

http://bse-atypical.blogspot.com/2009/11/seac-new-results-on-idiopathic.html



NEW RESULTS ON IDIOPATHIC BRAINSTEM NEURONAL CHROMATOLYSIS "All of the 15 cattle tested showed that the brains had abnormally accumulated PrP" 2009

http://bse-atypical.blogspot.com/2009/02/new-results-on-idiopathic-brainstem.html



AND THE USDA ET AL KNEW IT TOO ;


""These 9,200 cases were different because brain tissue samples were preserved with formalin, which makes them suitable for only one type of test--immunohistochemistry, or IHC."

THIS WAS DONE FOR A REASON!

THE IHC test has been proven to be the LEAST LIKELY to detect BSE/TSE in the bovine, and these were probably from the most high risk cattle pool, the ones the USDA et al, SHOULD have been testing. ...TSS

USDA 2003

We have to be careful that we don't get so set in the way we do things that we forget to look for different emerging variations of disease. We've gotten away from collecting the whole brain in our systems. We're using the brain stem and we're looking in only one area. In Norway, they were doing a project and looking at cases of Scrapie, and they found this where they did not find lesions or PRP in the area of the obex. They found it in the cerebellum and the cerebrum. It's a good lesson for us. Ames had to go back and change the procedure for looking at Scrapie samples. In the USDA, we had routinely looked at all the sections of the brain, and then we got away from it. They've recently gone back. Dr. Keller: Tissues are routinely tested, based on which tissue provides an 'official' test result as recognized by APHIS.

Dr. Detwiler: That's on the slaughter. But on the clinical cases, aren't they still asking for the brain? But even on the slaughter, they're looking only at the brainstem. We may be missing certain things if we confine ourselves to one area.

snip.............

Dr. Detwiler: It seems a good idea, but I'm not aware of it. Another important thing to get across to the public is that the negatives do not guarantee absence of infectivity. The animal could be early in the disease and the incubation period. Even sample collection is so important. If you're not collecting the right area of the brain in sheep, or if collecting lymphoreticular tissue, and you don't get a good biopsy, you could miss the area with the PRP in it and come up with a negative test. There's a new, unusual form of Scrapie that's been detected in Norway. We have to be careful that we don't get so set in the way we do things that we forget to look for different emerging variations of disease. We've gotten away from collecting the whole brain in our systems. We're using the brain stem and we're looking in only one area. In Norway, they were doing a project and looking at cases of Scrapie, and they found this where they did not find lesions or PRP in the area of the obex. They found it in the cerebellum and the cerebrum. It's a good lesson for us. Ames had to go back and change the procedure for looking at Scrapie samples. In the USDA, we had routinely looked at all the sections of the brain, and then we got away from it. They've recently gone back.

Dr. Keller: Tissues are routinely tested, based on which tissue provides an 'official' test result as recognized by APHIS .

Dr. Detwiler: That's on the slaughter. But on the clinical cases, aren't they still asking for the brain? But even on the slaughter, they're looking only at the brainstem. We may be missing certain things if we confine ourselves to one area.

snip...

FULL TEXT;

Completely Edited Version PRION ROUNDTABLE

Accomplished this day, Wednesday, December 11, 2003, Denver, Colorado

END...TSS


Suppressed peer review of Harvard study October 31, 2002.

October 31, 2002 Review of the Evaluation of the Potential for Bovine Spongiform Encephalopathy in the United States Conducted by the Harvard Center for Risk Analysis, Harvard School of Public Health and Center for Computational Epidemiology, College of Veterinary Medicine, Tuskegee University Final Report Prepared for U.S. Department of Agriculture Food Safety and Inspection Service Office of Public Health and Science Prepared by RTI Health, Social, and Economics Research Research Triangle Park, NC 27709 RTI Project Number 07182.024

http://www.fsis.usda.gov/oa/topics/BSE_Peer_Review.pdf



Sunday, February 14, 2010

[Docket No. FSIS-2006-0011] FSIS Harvard Risk Assessment of Bovine Spongiform Encephalopathy (BSE)

http://bseusa.blogspot.com/2010/02/docket-no-fsis-2006-0011-fsis-harvard.html



PLEASE SEE FULL TEXT 98 PAGES HERE ;

[Docket No. FSIS-2006-0011] FSIS Harvard Risk Assessment of Bovine Spongiform Encephalopathy (BSE)

http://www.fsis.usda.gov/OPPDE/Comments/2006-0011/2006-0011-1.pdf



Response to Public Comments on the Harvard Risk Assessment of Bovine Spongiform Encephalopathy

Update, October 31, 2005 INTRODUCTION The United States Department of Agriculture’s Food Safety and Inspection Service (FSIS) held a public meeting on July 25, 2006 in Washington, D.C. to present findings from the Harvard Risk Assessment of Bovine Spongiform Encephalopathy Update, October 31, 2005 (report and model located on the FSIS website: http://www.fsis.usda.gov/Science/Risk_Assessments/index.asp). Comments on technical aspects of the risk assessment were then submitted to FSIS. Comments were received from Food and Water Watch, Food Animal Concerns Trust (FACT), Farm Sanctuary, R-CALF USA, Linda A Detwiler, and Terry S. Singeltary. This document provides itemized replies to the public comments received on the 2005 updated Harvard BSE risk assessment. Please bear the following points in mind:

http://www.fsis.usda.gov/PDF/BSE_Risk_Assess_Response_Public_Comments.pdf



another question, just how long have these atypical BSE TSEs been around in the bovine ???


let's look at another case of atypical BSE in Germany way back in 1992 ;


Subject: atypical BSE reported in 1992 and conviently slaughterd and incinerated and then swept under rug for about 12 years Date: April 26, 2007 at 1:08 pm PST 1992

NEW BRAIN DISORDER

3. WHAT ABOUT REPORTS OF NEW FORM OF BSE?

THE VETERINARY RECORD HAS PUBLISHED AN ARTICLE ON A NEW BRAIN DISORDER OF CATTLE DISCOVERED THROUGH OUR CONTROL MEASURES FOR BSE. ALTHOUGH IT PRESENTS SIMILAR CLINICAL SIGNS TO BSE THERE ARE MAJOR DIFFERENCES IN THE HISTOPATHOLOGY AND INCUBATION PERIODS BETWEEN THE TWO. MUST EMPHASISE THAT THIS IS NOT BSE.

4. IS THIS NEW BRAIN DISORDER A THREAT?

WE DO NOT EVEN KNOW WHETHER THE AGENT OF THIS DISEASE IS TRANSMISSIBLE. IN ANY CASE, CASES SO FAR IDENTIFIED HAD SHOWN SIMILAR SYMPTOMS TO THOSE OF BSE, AND THEREFORE HAVE BEEN SLAUGHTERED AND INCINERATED, SO THAT IF A TRANSMISSIBLE AGENT WERE INVOLVED IT WOULD HAVE BEEN ELIMINATED. .......

http://web.archive.org/web/20030714222309/www.bseinquiry.gov.uk/files/yb/1992/10/26001001.pdf



2. The Collinge/Will dispute appears to rumble on. Dr. Collinge had told Dr. Tyrrell that Dr. Will's response to his criticism about sharing material had been ''quite unacceptable'' (in spite of it's apparently conciliatory tone). Apparently Professor Allen was now going to try and arrange a meeting to resolve the dispute. No action here for MAFF, although Mr. Murray may be interested.

3. Dr. Tyrrell regretted that the Committee had not seen the article on BBD. However he felt that for the time being NO specific action was called for. The most important need was to consider the possibility that the condition might be transmissible. As we have discussed, I suggested that we might circulate a paper to the members of the committee giving our appreciation of this condition (and perhaps of other non-BSE neurological conditions that had been identified in negative cases) and of any necessary follow up action. IF any Committee member felt strongly about this, or if the issue CAME TO A HEAD, we would call an interim meeting. He was happy with this approach. I would be grateful if Mr. Maslin could, in discussion with CVL and veterinary colleagues draft such a note, which will presumably very largely follow what Mr. Bradley's briefing paper has already said, taking account of DOH comments, We can then clear a final version with DOH before circulating it to Committee members.

http://web.archive.org/web/20030714222309/www.bseinquiry.gov.uk/files/yb/1992/10/29005001.pdf



IN CONFIDENCE

This is a highly competitive field and it really will be a pity if we allow many of the key findings to be published by overseas groups while we are unable to pursue our research findings because of this disagreement, which I hope we can make every effort to solve.

http://web.archive.org/web/20030714222309/www.bseinquiry.gov.uk/files/yb/1992/10/26002001.pdf



COLLINGE THREATENS TO GO TO MEDIA


http://web.archive.org/web/20030714222309/www.bseinquiry.gov.uk/files/yb/1992/12/16005001.pdf



Wednesday, August 20, 2008

Bovine Spongiform Encephalopathy Mad Cow Disease typical and atypical strains, was there a cover-up ? August 20, 2008


http://bse-atypical.blogspot.com/2008/08/bovine-spongiform-encephalopathy-mad.html




sporadic cjd in farmers and farmers wives with BSE mad cow herds


http://cjdmadcowbaseoct2007.blogspot.com/2008/06/novel-human-disease-with-abnormal-prion.html




end...TSS





----- Original Message -----
From: Jerry Saliki
To: Terry S. Singeltary Sr.
Cc: Dongyue.Zhuang@ARS.USDA.GOV ; Katherine.ORourke@ARS.USDA.GOV ; Aru.Balachandran@inspection.gc.ca ; editorial@jvdi.org ; jsaliki@jvdi.org ; cjdvoice@yahoogroups.com ; editor1@uga.edu
Sent: Tuesday, June 15, 2010 3:43 PM
Subject: RE: Research Project: Transmissible Spongiform Encephalopathies: Identification of atypical scrapie in Canadian sheep


Dear Mr. Singeltary:

Thank you for the "condensed" version of your concerns. Your main concern appears to be te statement "There is as yet no evidence for transmission of atypical scrapie". However, a closer look at the article we published in the Journal of Veterinary Diagnostic Investigation (JVDI) found no such sentence in the article. On the contrary, the authors [appropriately] discussed in the second paragraph of page 411 the question of transmissibility of atypical scrapie. If the sentence that troubles you was published somewhere, the JVDI has no responsibility or accountability for that. If there is anything else in the published article that you wish to comment on, you may formulate your comment in the form of a 1-2-paragraph letter to the editor.

Sincerely,

Jeremiah T. Saliki, DVM, PhD, DACVM
Editor-in-Chief, Journal of Veterinary Diagnostic Investigation
Website: http://jvdi.org



SNIP...END...TSS




1ST UPDATE JUNE 11, 2010



----- Original Message -----
From: Terry S. Singeltary Sr.
To: Jerry Saliki
Cc: Dongyue.Zhuang@ARS.USDA.GOV ; Katherine.ORourke@ARS.USDA.GOV ; Aru.Balachandran@inspection.gc.ca ; editorial@jvdi.org ; jsaliki@jvdi.org ; subscription@jvdi.org ; cjdvoice@yahoogroups.com ; BSE-L@LISTS.AEGEE.ORG ; editor1@uga.edu
Sent: Friday, June 11, 2010 12:37 PM
Subject: Re: Research Project: Transmissible Spongiform Encephalopathies: Identification of atypical scrapie in Canadian sheep


Greetings Dr. Saliki et al at JVDI and ARS et al,


I apologize for being so 'incomprehensible' in my comments to JVDI about the study recently published in JVDI and at the ARS site titled "Identification of atypical scrapie in Canadian sheep".


Dr. Saliki JVDI stated ;


" I request that you condense your concerns into a paragraph or a series of bullet points, for further consideration. I would also like to inform you that articles published in the Journal of Veterinray Diagnostic Investigation are peer-reviewed by individuals with expertise in the various fields."


end


Thank you very much Sir for allowing me to comment for consideration at JVDI. I just thought your journal would want to know when something published might be in question. please see my condensed comment to this study next, and sources to follow. I hope you find this more comprehensible. ...


Thank You,
With Kindest Regards,
Terry


condensed version as follows ;


Greetings Dr. Saliki and JVDI et al,


In reply to ;


Identification of atypical scrapie in Canadian sheep


http://jvdi.org/cgi/content/abstract/22/3/408?maxtoshow=&hits=10&RESULTFORMAT=&fulltext=prion&searchid=1&FIRSTINDEX=0&volume=22&issue=3&resourcetype=HWCIT



Research Project: Transmissible Spongiform Encephalopathies: the Role of Genetics, Strain Variation, and Environmental Contamination in Disease Control Location: Animal Diseases Research

Title: Identification of atypical scrapie in Canadian sheep

Authors

Mitchell, G - Orourke, Katherine Harrington, N - Soutyrine, A - Simmons, M - Dudas, S - Zhuang, Dongyue Laude, H - Balachandran, A -

Submitted to: Canadian Veterinary Journal Publication Type: Peer Reviewed Journal Publication Acceptance Date: December 3, 2009 Publication Date: May 1, 2010 Citation: Mitchell, G.B., Orourke, K.I., Harrington, N.P., Soutyrine, A., Simmons, M.M., Dudas, S., Zhuang, D., Laude, H., Balachandran, A. 2010. Identification of atypical scrapie in Canadian sheep. Canadian Veterinary Journal. 22(3):402-408.


http://www.ars.usda.gov/research/publications/Publications.htm?seq_no_115=245110



>>> There is as yet no evidence for transmission of atypical scrapie


I find this statement to be incorrect. Atypical Scrapie is consistently transmissible within AHQ homozygous sheep, and the disease phenotype is preserved on sub-passage. The Nor-98 atypical Scrapie transmits to mice and to sheep through intracerebral inoculation in transgenic mice and sheep. There are some data even suggesting that it may also be transmissible orally to sheep of different genotypes to date (see SEAC reference). We also know that some typical Scrapie strains will transmit to primate by their non-forced oral consumption of Scrapie infected materials.


I find it very disturbing and irresponsible that the O.I.E. and U.S.D.A. et al, have made legal, the trading of the atypical Scrapie Nor-98 strain as a non-health issue (as with typical Scrapie strains), when we have science showing that they are a potential health threat, and when you have the Nobel Prize winner for the Prion, Dr. Stanley Prusiner voicing his concern, (see reference). Please remember also, testing on humans has never been done. So to continue to theorize or wish that the atypical Scrapie strains and or typical Scrapie strains will not transmit to man or animal is not scientifically sound, and needlessly puts at risk both man and animal to Transmissible Spongiform Encephalopathy around the globe via trade.


Terry S. Singeltary Sr.
P.O. Box 42
Bacliff, Texas USA 77518
flounder9@verizon.net



additional comments as follows ;



Greetings again Dr. Saliki et al,


I have had a passion for Transmissible Spongiform Encephalopathy since the death of my Mom to the Heidenhain Variant Creutzfeldt Jakob disease, one of 6+ strains of the sporadic CJD's. Sporadic CJD simply meaning CJD from unknown route and source of the TSE agent, and here in the USA, that could be many different routes and sources, if you consider the many different TSE strains in different species in North America, and then think 'friendly fire' there from. For a few years now there seems to be a rise here in the U.S.A. of sporadic CJD strains of 'unknown phenotype', with ;


5 Includes 28 cases in which the diagnosis is pending, and 17 inconclusive cases;


6 Includes 28 (24 from 2010) cases with type determination pending in which the diagnosis of vCJD has been excluded


http://www.cjdsurveillance.com/pdf/case-table.pdf




I should remind you of an old statement ;


If the scrapie agent is generated from ovine DNA and thence causes disease in other species, then perhaps, bearing in mind the possible role of scrapie in CJD of humans (Davinpour et al, 1985), scrapie and not BSE should be the notifiable disease. ...


http://collections.europarchive.org/tna/20090505194948/http://bseinquiry.gov.uk/files/yb/1988/06/08004001.pdf




and these findings now ;


Similarities between Forms of Sheep Scrapie and Creutzfeldt-Jakob Disease Are Encoded by Distinct Prion Types

snip...

Different Scrapie Prion Types Show Similarities to Human Prion Types: PrPsc Deposition Pattern and Western Blot Results


http://ajp.amjpathol.org/cgi/content/abstract/175/6/2566



please see studies and findings below as well ;


Sporadic CJD type 1 and atypical/ Nor98 scrapie are characterized by fine (reticular) deposits,


see also ;


All of the Heidenhain variants were of the methionine/ methionine type 1 molecular subtype.


http://cjdusa.blogspot.com/2009/09/co-existence-of-scrapie-prion-protein.html



SOURCE REFERENCES BELOW ;


Research article

The natural atypical scrapie phenotype is preserved on experimental transmission and sub-passage in PRNP homologous sheep

Marion M Simmons1 , Timm Konold1 , Lisa Thurston1 , Susan J Bellworthy1 , Melanie J Chaplin2 and S Jo Moore1

1 Department of Pathology, Veterinary Laboratories Agency Weybridge, New Haw, Addlestone KT15 3NB, UK

2 Molecular Pathogenesis and Genetics Department, Veterinary Laboratories Agency Weybridge, New Haw, Addlestone KT15 3NB, UK

author email corresponding author email

BMC Veterinary Research 2010, 6:14doi:10.1186/1746-6148-6-14


http://www.biomedcentral.com/1746-6148/6/14



4. Transmission of atypical scrapie It has recently18 been demonstrated that atypical scrapie is experimentally transmissible to mice and sheep, primarily through intracerebral injection. There are some data suggesting that it may also be transmissible orally to sheep of different genotypes.


http://www.seac.gov.uk/pdf/positionstatement-sheep-subgroup.pdf



18 Le Dur A., Béringue V., Andréoletti O., Reine F., Laï T.H., Baron T., Bratberg B., Vilotte J.- L., Sarradin P., Benestad S.L. and Laude H.(2005)

Edited by Stanley B. Prusiner, University of California, San Francisco, CA (received for review March 21, 2005)

A newly identified type of scrapie agent can naturally infect sheep with resistant PrP genotypes.

Here we report that both Nor98 and discordant cases, including three sheep homozygous for the resistant PrPARR allele (A136R154R171), efficiently transmitted the disease to transgenic mice expressing ovine PrP, and that they shared unique biological and biochemical features upon propagation in mice. These observations support the view that a truly infectious TSE agent, unrecognized until recently, infects sheep and goat flocks and may have important implications in terms of scrapie control and public health.

PNAS 102, 16031-16036


http://www.pnas.org/content/102/44/16031.abstract



IN CONFIDENCE

TRANSMISSION TO CHIMPANZEES

We cannot say that Scrapie will not transmit to Chimpanzees.


http://collections.europarchive.org/tna/20080102222950/http://www.bseinquiry.gov.uk/files/yb/1990/09/23001001.pdf



EVIDENCE OF SCRAPIE IN SHEEP AS A RESULT OF FOOD BORNE EXPOSURE

2. It was agreed that there was evidence of scrapie in sheep as a result of food borne exposure. This is provided by the statistically significant increase in the incidence of sheep scrape from 1985, as determined from analyses of the submissions made to VI Centres, and from individual case and flock incident studies. As the working hypothesis is that there has been recycling of infected cattle tissues which has augmented the epidemic in cattle the continued infection of sheep with the BSE agent, via the food borne source, cannot be excluded. There is therefore also a possibility that the BSE agent may have become indemic in the sheep population, but it is impossible to design any short-term research programme to elucidate this. ...


http://web.archive.org/web/20030517224223/http://www.bseinquiry.gov.uk/files/yb/1994/02/07002001.pdf



1. Inclusion of “atypical” scrapie: The scientific evidence indicates that “atypical” scrapie, also referred to as Nor-98, Nor-98-like, or non-classical scrapie, is not the same disease as classical scrapie. Further, “atypical” scrapie does not meet the criteria for listing diseases of trade concern by the OIE, as described in Chapter 2.1.1 of the Code. The United States recommends that the scope of this chapter be limited to classical scrapie in sheep and goats. Further, the United States recommends that OIE clearly adopt the position that “atypical” scrapie represents a distinct disease entity from classical scrapie and that it not be a listed disease. • There is no evidence that “atypical” scrapie is a contagious disease.


http://www.aphis.usda.gov/import_export/animals/oie/downloads/tahc_mar-sep08/tahc-scrapie-77-mar08_cmt.pdf



Monday, November 30, 2009

USDA AND OIE COLLABORATE TO EXCLUDE ATYPICAL SCRAPIE NOR-98 ANIMAL HEALTH CODE


http://nor-98.blogspot.com/2009/11/usda-and-oie-collaborate-to-exclude.html



1: J Infect Dis 1980 Aug;142(2):205-8

Oral transmission of kuru, Creutzfeldt-Jakob disease, and scrapie to nonhuman primates.

Gibbs CJ Jr, Amyx HL, Bacote A, Masters CL, Gajdusek DC.

Kuru and Creutzfeldt-Jakob disease of humans and scrapie disease of sheep and goats were transmitted to squirrel monkeys (Saimiri sciureus) that were exposed to the infectious agents only by their nonforced consumption of known infectious tissues. The asymptomatic incubation period in the one monkey exposed to the virus of kuru was 36 months; that in the two monkeys exposed to the virus of Creutzfeldt-Jakob disease was 23 and 27 months, respectively; and that in the two monkeys exposed to the virus of scrapie was 25 and 32 months, respectively. Careful physical examination of the buccal cavities of all of the monkeys failed to reveal signs or oral lesions. One additional monkey similarly exposed to kuru has remained asymptomatic during the 39 months that it has been under observation.

snip...

The successful transmission of kuru, Creutzfeldt-Jakob disease, and scrapie by natural feeding to squirrel monkeys that we have reported provides further grounds for concern that scrapie-infected meat may occasionally give rise in humans to Creutzfeldt-Jakob disease.

PMID: 6997404


http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6997404&dopt=Abstract



Recently the question has again been brought up as to whether scrapie is transmissible to man. This has followed reports that the disease has been transmitted to primates. One particularly lurid speculation (Gajdusek 1977) conjectures that the agents of scrapie, kuru, Creutzfeldt-Jakob disease and transmissible encephalopathy of mink are varieties of a single "virus". The U.S. Department of Agriculture concluded that it could "no longer justify or permit scrapie-blood line and scrapie-exposed sheep and goats to be processed for human or animal food at slaughter or rendering plants" (ARC 84/77)" The problem is emphasised by the finding that some strains of scrapie produce lesions identical to the once which characterise the human dementias"

Whether true or not. the hypothesis that these agents might be transmissible to man raises two considerations. First, the safety of laboratory personnel requires prompt attention. Second, action such as the "scorched meat" policy of USDA makes the solution of the acrapie problem urgent if the sheep industry is not to suffer grievously.

snip...

76/10.12/4.6


http://web.archive.org/web/20010305223125/www.bseinquiry.gov.uk/files/yb/1976/10/12004001.pdf



all this i have documented here ;


see scrapie in CJD of humans (Davinpour et al, 1985) and more here ;


Sunday, April 18, 2010

SCRAPIE AND ATYPICAL SCRAPIE TRANSMISSION STUDIES A REVIEW 2010


http://scrapie-usa.blogspot.com/2010/04/scrapie-and-atypical-scrapie.html




Wednesday, March 3, 2010

NOR-98 ATYPICAL SCRAPIE USA 4 CASES DETECTED JANUARY 2010


http://nor-98.blogspot.com/2010/03/nor-98-atypical-scrapie-usa-4-cases.html





Friday, January 29, 2010

14th International Congress on Infectious Diseases H-type and L-type Atypical BSE January 2010 (special pre-congress edition)

see page 114 ;


http://ww2.isid.org/Downloads/14th_ICID_ISE_Abstracts.pdf



PLEASE SEE my journal publishings on TSE as a layperson 1997-2010 here ;


http://bse-atypical.blogspot.com/2010/01/14th-international-congress-on.html



Thursday, June 03, 2010

Prion Strain Mutation and Selection John Collinge

MEDICINE


http://chronic-wasting-disease.blogspot.com/2010/06/prion-strain-mutation-and-selection.html



Friday, May 14, 2010

Prion Strain Mutation Determined by Prion Protein Conformational Compatibility and Primary Structure

Published Online May 13, 2010 Science DOI: 10.1126/science.1187107 Science Express Index


http://www.sciencemag.org/cgi/content/abstract/science.1187107



see full text and more here ;


http://chronic-wasting-disease.blogspot.com/2010/05/prion-strain-mutation-determined-by.html



Molecular, Biochemical and Genetic Characteristics of BSE in Canada


http://bse-atypical.blogspot.com/2010/05/molecular-biochemical-and-genetic.html



To date the OIE/WAHO assumes that the human and animal health standards set out in the BSE chapter for classical BSE (C-Type) applies to all forms of BSE which include the H-type and L-type atypical forms. This assumption is scientifically not completely justified and accumulating evidence suggests that this may in fact not be the case. Molecular characterization and the spatial distribution pattern of histopathologic lesions and immunohistochemistry (IHC) signals are used to identify and characterize atypical BSE. Both the L-type and H-type atypical cases display significant differences in the conformation and spatial accumulation of the disease associated prion protein (PrPSc) in brains of afflicted cattle. Transmission studies in bovine transgenic and wild type mouse models support that the atypical BSE types might be unique strains because they have different incubation times and lesion profiles when compared to C-type BSE. When L-type BSE was inoculated into ovine transgenic mice and Syrian hamster the resulting molecular fingerprint had changed, either in the first or a subsequent passage, from L-type into C-type BSE. In addition, non-human primates are specifically susceptible for atypical BSE as demonstrated by an approximately 50% shortened incubation time for L-type BSE as compared to C-type. Considering the current scientific information available, it cannot be assumed that these different BSE types pose the same human health risks as C-type BSE or that these risks are mitigated by the same protective measures.


http://www.prionetcanada.ca/detail.aspx?menu=5&dt=293380&app=93&cat1=387&tp=20&lk=no&cat2



please see full text ;

Wednesday, March 31, 2010

Atypical BSE in Cattle


http://bse-atypical.blogspot.com/2010/03/atypical-bse-in-cattle-position-post.html



http://bse-atypical.blogspot.com/2009/10/atypical-bse-bse-and-other-human-and.html



Tuesday, June 1, 2010

USA cases of dpCJD rising with 24 cases so far in 2010


http://cjdtexas.blogspot.com/2010/06/usa-cases-of-dpcjd-rising-with-24-cases.html



Monday, April 5, 2010

UPDATE - CJD TEXAS 38 YEAR OLD FEMALE WORKED SLAUGHTERING CATTLE EXPOSED TO BRAIN AND SPINAL CORD MATTER


http://prionunitusaupdate2008.blogspot.com/2010/04/update-cjd-texas-38-year-old-female.html



Archive Number 20100405.1091 Published Date 05-APR-2010

Subject PRO/AH/EDR> Prion disease update 1010 (04)

snip...

[Terry S. Singeltary Sr. has added the following comment:

"According to the World Health Organisation, the future public health threat of vCJD in the UK and Europe and potentially the rest of the world is of concern and currently unquantifiable. However, the possibility of a significant and geographically diverse vCJD epidemic occurring over the next few decades cannot be dismissed.


The key word here is diverse. What does diverse mean? If USA scrapie transmitted to USA bovine does not produce pathology as the UK c-BSE, then why would CJD from there look like UK vCJD?"



http://www.promedmail.org/pls/apex/f?p=2400:1001:568933508083034::NO::F2400_P1001_BACK_PAGE,F2400_P1001_PUB_MAIL_ID:1000,82101



ATYPICAL BSE MORE VIRULENT TO HUMANS THAN UK STRAIN

18 January 2007 - Draft minutes of the SEAC 95 meeting (426 KB) held on 7 December 2006 are now available.

snip...

64. A member noted that at the recent Neuroprion meeting, a study was presented showing that in transgenic mice BSE passaged in sheep may be more virulent and infectious to a wider range of species than bovine derived BSE.

Other work presented suggested that BSE and bovine amyloidotic spongiform encephalopathy (BASE) MAY BE RELATED. A mutation had been identified in the prion protein gene in an AMERICAN BASE CASE THAT WAS SIMILAR IN NATURE TO A MUTATION FOUND IN CASES OF SPORADIC CJD.

snip...


http://www.seac.gov.uk/minutes/95.pdf



3:30 Transmission of the Italian Atypical BSE (BASE) in Humanized Mouse

Models Qingzhong Kong, Ph.D., Assistant Professor, Pathology, Case Western Reserve University

Bovine Amyloid Spongiform Encephalopathy (BASE) is an atypical BSE strain discovered recently in Italy, and similar or different atypical BSE cases were also reported in other countries. The infectivity and phenotypes of these atypical BSE strains in humans are unknown. In collaboration with Pierluigi Gambetti, as well as Maria Caramelli and her co-workers, we have inoculated transgenic mice expressing human prion protein with brain homogenates from BASE or BSE infected cattle. Our data shows that about half of the BASE-inoculated mice became infected with an average incubation time of about 19 months; in contrast, none of the BSE-inoculated mice appear to be infected after more than 2 years.

***These results indicate that BASE is transmissible to humans and suggest that BASE is more virulent than classical BSE in humans.***

6:30 Close of Day One


http://www.healthtech.com/2007/tse/day1.asp



SEE STEADY INCREASE IN SPORADIC CJD IN THE USA FROM 1997 TO 2006. SPORADIC CJD CASES TRIPLED, with phenotype of 'UNKNOWN' strain growing. ...


http://www.cjdsurveillance.com/resources-casereport.html



There is a growing number of human CJD cases, and they were presented last week in San Francisco by Luigi Gambatti(?) from his CJD surveillance collection.

He estimates that it may be up to 14 or 15 persons which display selectively SPRPSC and practically no detected RPRPSC proteins.


http://www.fda.gov/ohrms/dockets/ac/06/transcripts/1006-4240t1.htm



http://www.fda.gov/ohrms/dockets/ac/06/transcripts/2006-4240t1.pdf



2008 - 2010

The statistical incidence of CJD cases in the United States has been revised to reflect that there is one case per 9000 in adults age 55 and older. Eighty-five percent of the cases are sporadic, meaning there is no known cause at present.


http://www.cjdfoundation.org/fact.html



Friday, November 30, 2007

CJD QUESTIONNAIRE USA CWRU AND CJD FOUNDATION


http://cjdquestionnaire.blogspot.com/



Meeting of the Transmissible Spongiform Encephalopathies Committee On June 12, 2009 (TRANSCRIPT)


http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/BloodVaccinesandOtherBiologics/TransmissibleSpongiformEncephalopathiesAdvisoryCommittee/UCM171810.pdf



Meeting of the Transmissible Spongiform Encephalopathies Committee On June 12, 2009 (Singeltary submission)


http://tseac.blogspot.com/2009/05/meeting-of-transmissible-spongiform.html



Saturday, June 13, 2009

Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob disease in the United States 2003 revisited 2009


http://cjdusa.blogspot.com/2009/06/monitoring-occurrence-of-emerging-forms.html



Friday, February 05, 2010

New Variant Creutzfelt Jakob Disease case reports United States 2010 A Review


http://vcjd.blogspot.com/2010/02/new-variant-creutzfelt-jakob-disease.html



Saturday, January 2, 2010

Human Prion Diseases in the United States January 1, 2010 ***FINAL***


http://prionunitusaupdate2008.blogspot.com/2010/01/human-prion-diseases-in-united-states.html



my comments to PLosone here ;



http://www.plosone.org/annotation/listThread.action?inReplyTo=info%3Adoi%2F10.1371%2Fannotation%2F04ce2b24-613d-46e6-9802-4131e2bfa6fd&root=info%3Adoi%2F10.1371%2Fannotation%2F04ce2b24-613d-46e6-9802-4131e2bfa6fd




Terry S. Singeltary Sr.
P.O. Box 42
Bacliff, Texas USA 77518





----- Original Message -----

From: Jerry Saliki
To: Terry S. Singeltary Sr.
Cc: Dongyue.Zhuang@ARS.USDA.GOV ; Katherine.ORourke@ARS.USDA.GOV ; Aru.Balachandran@inspection.gc.ca ; editorial@jvdi.org ; jsaliki@jvdi.org ; subscription@jvdi.org ; cjdvoice@yahoogroups.com ; BSE-L@LISTS.AEGEE.ORG ; editor1@uga.edu
Sent: Wednesday, June 09, 2010 8:22 AM
Subject: RE: Research Project: Transmissible Spongiform Encephalopathies: Identification of atypical scrapie in Canadian sheep


Dear Mr. Singletary:

Thank you for your recent message regarding atypical scrapie in Canadian sheep. Upon reading your message, I find it to be rather incomprehensible. I request that you condense your concerns into a paragraph or a series of bullet points, for further consideration. I would also like to inform you that articles published in the Journal of Veterinray Diagnostic Investigation are peer-reviewed by individuals with expertise in the various fields.


Sincerely,

Jeremiah T. Saliki, DVM, PhD, ACVM
Editor-in-Chief, Journal of Veterinary Diagnostic Investigation
Website: http://jvdi.org


END...




Terry S. Singeltary Sr.
P.O. Box 42
Bacliff, Texas USA 77518