Types or Strains: What Classifies Prion Diseases?
Wiebke M. Wemheuer,1 Sylvie L. Benestad,3 Arne Wrede,1 Wilhelm E. Wemheuer,2 Tatjana Pfander,1 Bertram Brenig2 and Walter J. Schulz-Schaeffer1 1Department of Neuropathology; University Medical Center; Goettingen, Germany; 2Institute of Veterinary Medicine; Georg August University; Goettingen, Germany; 3National Veterinary Institute; Oslo, Norway
Key words: prion types, prion strains, CJD, sheep scrapie, stability
In the 1950s scrapie in small ruminants was classified as a “Slow Virus Disease” (Sigurdsson, et al. Br V et J 1954; 110:314–54). Different incubation times upon transmission from scrapie to mice were thought to originate from different virus strains (Dickinson, et al. J CompPathol 1968; 78:293–9). Along with the “prion hypothesis” and the actuality that the conformation of proteins determines their properties the idea was established that strains exist due to conformational differences of the pathological prion protein (PrPSc). By definition, prion strains are identified after transmission of an isolate to a new host species (Aguzzi, et al. Rev Mol Cell Biol 2007; 8:552–61). However, in human Creutzfeldt-Jakob disease (CJD) the existence of types in humans as the original host has been described and conformational differences are presumably the reason for different cleavage sites of proteinase K (Parchi, et al. AnnNeurol 1996; 39:767–78). Our own evaluation of sporadic CJD cases and sheep scrapie samples provides proof that types in prion diseases are present across species, but they need to be defined and clearly separated from strains. Using the PrPSc deposition pattern and PrPSc stability against denaturation with GdnHCl as parameters we found that sporadic CJD type 1 and atypical/Nor98 scrapie as well as sporadic CJD type 2 and classical scrapie show striking similarities (Wemheuer, et al. Am J Pathol 2009; 175:2566–73). From our results and ongoing research we conclude that types with distinct conformational motives are the major determinants within a prion disease; a type may also contain different strains, but a strain cannot belong to more than one prion type.
A Typical/Nor98 Scrapie Infectivity in Sheep Peripheral Tissues
Caroline Lacroux,1 Leonor Orge,2,* Sylvie L. Benestad,3 Vincent Beringue,4 Claire Litaise,1 Stéphanie Simon,5 Hugh Simmons,6 Séverine Lugan,1 Fabien Corbière,1 Pierrette Costes,1 Nathalie Morel,5 François Schelcher1 and Olivier Andréoletti1,* 1UMR INRA ENVT 1225; Interactions Hôte Agent Pathogène; Ecole Nationale Vétérinaire de Toulouse; Toulouse, France; 2Laboratório Nacional de Investigação Veterinária; Estrada de Benfica, Lisboa, Portugal; 3National Veterinary Institute; Postboks; Oslo, Norway; 4INRA UR892; Virologie Immunologie Moléculaires; INRA; Jouy-en-Josas; 5CEA; Service de Pharmacologie et d’Immunoanalyse; IBiTec-S; DSV; CEA/Saclay; Gif sur Yvette cedex, France; 6VLA Weybridge; ASU; New Haw; Addlestone, Surrey UK
Key words: atypical, scrapie, peripheral tissues infectivity
Atypical/Nor98 scrapie was first identified in 1998 in Norway. It is now considered as a world widespread disease of small ruminants and currently represents more than the half of the detected TSE cases in Europe. Atypical/Nor98 scrapie agent biology and pathogenesis in its natural host is still poorly understood. Conversely to BSE and other small ruminants TSE agents, the ARR PrP allele does not provide protection against the disease, making the genetic selection policy inefficient to eradicate it. Based on the absence of detectable abnormal PrPSc in peripheral tissues the human and animal exposure risk to this specific TSE agent has been considered as low. In the present study we first demonstrated that infectivity can accumulate, even if no abnormal PrP is detectable, in lymphoid tissues, nerves and muscles from natural and experimental Atypical/Nor98 scrapie cases. We furthermore demonstrated that, in comparison to other TSE agents, samples containing massive amount of Atypical/Nor98 scrapie infectivity can remain PrPSc negative. This feature probably impacts our perception of Atypical/Nor98 scrapie prevalence and spreading in field population. We finally evaluated, in both Atypical/Nor98 and classical scrapie cases, the infectivity loads accumulating in peripheral tissues that currently enter unrestricted into the food chain. The obtained results indicate that dietary exposure risk to small ruminants TSE agents is much higher than commonly believed. This conclusion raises the question of the potential capacities such TSE agents to transmit in other species.
Discrimination of Ovine BSE from Classical Scrapie, CH1641-like and Nor98 Isolates by a Novel Conformational Stability Assay
Laura Pirisinu, Elena Esposito, Sergio Migliore, Michele Di Bari, Claudia D’Agostino, Paola Fazzi, Luisella Morelli, Umberto Agrimi and Romolo Nonno Istituto Superiore di Sanità; Rome, Italy
Key words: strain, scrapie, CH1641_like, ovine BSE, conformatiional stability
TSEs of small ruminants include classical and atypical (Nor98) scrapie, which can be discriminated from experimental ovine BSE by PrPres molecular typing. However, some natural sheep isolates have been described in sheep showing molecular similarities with BSE, as determined by the PK cleavage site of PrPSc. These were named CH1641-like due to molecular similarities with the experimental CH1641 strain.
Aim of this study was to analyse the conformational stability of PrPSc from sheep TSE isolates by a new conformational stability and solubility assay (CSSA) that we have recently developed. CSSA employs denaturation with increasing concentrations of GdnHCl and differential centrifugation and allows to determine the [GdnHCl]1/2 value of PrPSc aggregates without PK digestion.
CNS samples from sheep with natural scrapie (n = 13), experimental CH1641 (n = 1) and experimental BSE (n = 3) were analysed. The 13 natural scrapie isolates included classical scrapie (n = 5), Nor98 (n = 5) and CH1641-like (n = 3) cases.
Denaturation curves showed strain-specific conformational stabilities, with [GdnHCl]1/2 values ranging from 1.96 to 2.31 M for classical scrapie, from 2.06 to 2.88 M for CH1641 and CH1641-like and from 1.26 to 1.43 M for Nor98. BSE samples showed the highest conformational stability compared to all other samples, with [GdnHCl]1/2 values >3, 5 M.
Our preliminary results suggest that CSSA reveals strain-specific PrPSc conformational stabilities of ovine prion isolates. The higher conformational stability of sheep BSE compared to all other known TSEs of sheep could be exploited for a more reliable and unequivocal scrapie/BSE discrimination.
Atypical Scrapie in Goats-Pathological and Epidemiological Characterization and Relevance
Carla Machado,1 Ana Oliveira,2 Carla Lima,1 Paula Tavares,1 Paula Almeida,1 Cristina Ochoa,1 João Silva,1 Manuel Ramos,1 Maria José M. Pinto2 and M. Leonor Orge1 1Laboratório Nacional de Investigação Veterinária; Instituto Nacional de Recursos Biológicos; Lisboa, Portugal; 2Direcção Geral de Veterinária; Largo da Academia Nacional de Belas Artes; Lisboa, Portugal
Key words: caprines, atypical scrapie, pathology, epidemiology, prnp genotype
Scrapie affects sheep and goats, being the most common form of transmissible spongiform encephalopathies, which include Creutzfeldt-Jakob Disease (CJD) in humans and Bovine Spongiform Encephalopathy (BSE), recognized for over 250 years in several European countries. As no obvious clinical or epidemiological connection to human disease has been revealed to date, scrapie is considered non-pathogenic for humans, at least under natural conditions. However, since it has been shown that sheep could be experimentally infected with BSE, possibility has been raised that BSE could have been accidentally introduced in this species. This has prompted in 2002 a surveillance plan for scrapie in small ruminants by the European Union in all member states.
In 2005, the first natural BSE case was identified in a French goat and four years later, a Scottish goat, from a retrospective study, showed bioassay results indistinguishable from BSE (STEG, 2009).
Although natural classical caprine scrapie is considered rare, it has been reported in many countries. Regarding atypical scrapie in goats data is very limited, representing 1–2% of scrapie positive cases in EU-27. They have been reported in France, Italy, Spain and Portugal (EC, 2008).
Between 2003 and 2009, a total of 415,340 small ruminants were screened and atypical scrapie was identified in 365 Portuguese sheep and 4 goats.
In the present study, we aimed to describe the phenotype features as well as Prnp sequence of these atypical caprine scrapie cases, comparing to previous reported data and thus contributing to understand this form of scrapie in this species.
Nervous Dissemination of BSE in Orally Infected Goats
Frédéric Lantier,1,* Christine Hoffmann,2,* Patricia Berthon,1 Susanne Freyse,2 Isabelle Lantier,1 Anne Balkema-Buschmann,2 Christelle Rossignol,1 Kerstin Tauscher,2 Hervé Le Roux,1 Francis Barillet,3 Olivier Andréoletti4 and Martin H. Groschup2 *First authors 1INRA; IASP; Nouzilly, France; 2FLI-INEID; Riems, Germany; 3INRA; SAGA; Toulouse, France; 4INRA-ENVT; IHAP; Toulouse, France
Key words: BSE, goat, disease-associated PrP, pathogenesis
As the consumption of products from naturally BSE-infected goats represents a potential exposure risk to humans, we investigated tissue distribution of BSE in orally challenged goats of different PRNP genotypes. Healthy groups of three goats carrying three scrapie-susceptible PRNP genotypes [I142R211Q222/IRQ: wild type (WT), IRQ/IQQ: Q211 mutated (Q211) and IRQ/IRK: K222 mutated (K222)] were orally challenged with cattle (INRA) or goat (FLI) derived BSE and sequentially culled at 6, 12, 17 and 24–25 months post-inoculation (mpi). At necropsies, a large number of samples was taken for the detection of disease-associated PrP (PrPD) (IHC, ELISA, WB) and infectivity (transgenic bioassays).
First traces of PrPD in preclinical goats were detectable 12 mpi in the Ganglia coeliacum of a WT goat and in follicles of the ileocaecal junction in a Q211 goat. At 17 mpi, PrPD was localised in the ileal enteric nervous system of 2/3 WT goats and a Q211 goat. This goat also contained PrPD accumulation in the central nervous system (obex and thoracic spinal cord). Another Q211 goat showed PrPD in the obex only. First clinical symptoms were observed in 4 WT goats after 24–25 mpi, revealing a severe spongiform encephalopathy with a PrPD accumulation in the brain stem. Until now no PrPD was detectable in tonsils.
In this study incubation periods for BSE in goats were longer than for scrapie and are influenced by the PRNP genotypes. Pathogenic pathways, mainly limited to neuronal tissues, restrict the usefulness of lymphoid tissue biopsies for ante-mortem diagnosis of BSE-infected goats.
Assessing the Risk of Sheep BSE Transmission to Humans Chris Plinston, Nora Hunter, Jim Foster, Patricia Hart, Jean C. Manson and Rona M. Barron Neuropathogenesis Division; The Roslin Institute and R(D)SVS; University of Edinburgh; Edinburgh, Scotland UK
Key words: human, transgenic, sheep BSE,
Strain typing studies have shown that the same strain of TSE agent is responsible for BSE in cattle and vCJD in humans. However, transmission studies of cattle BSE to humans using transgenic mice expressing human PrP have shown limited transmissibility, suggesting the presence of a substantial transmission barrier. To investigate this transmission barrier further, gene targeted transgenic mice expressing human PrP with the codon 129 polymorphism (HuMM, HuMV and HuVV) have been challenged with cattle BSE and Experimental Sheep BSE (Exp-ShBSE). BSE has not been identified in sheep in the field, but sheep have been shown to susceptible to experimental infection. Mice inoculated with cattle BSE failed to show any evidence of disease transmission. However following inoculation with Exp-ShBSE, 18/23 HuMM transgenic mice showed positive TSE pathology (400–750 dpi) in the form of vacuolation and/or PrP deposition, targeted mainly to the thalamic region. While no clinical signs of disease were reported in any of the HuTg mice receiving Exp-ShBSE, positive clinical and pathological signs of disease were observed in both control 129/Ola mice and gene targeted bovine transgenic mice. Control lines showed similar pathology, and incubation time ratios with both cattle BSE and Exp-ShBSE, however Exp-ShBSE incubation times were shorter (~70–80 days) than those observed following cattle BSE inoculation. These data suggest a difference in susceptibility of HuMM mice to the BSE agent following propagation in either cattle or sheep. Experiments to establish the titre of BSE in sheep brainstem are underway.
4.2.9 A further hypothesis to explain the occurrence of BSE is the emergence or selection of a strain or strains of the scrapie agent pathogenic for cattle. Mutations of the scrapie agent. which can occur after a single passage in mice. have been well documented (9). This phenomenon cannot be dismissed for BSE. but given the form of the epidemic and the geographically widespread occurrence of BSE, such a hypothesis" would require the emergence of a mutant scrapie strain simultaneously in a large . number of sheep flocks, or cattle. throughout the country. Also. if it resulted "from a localised chance transmission of the scrapie strain from sheep to cattle giving rise , . to a mutant. a different pattern of disease would have been expected: its range would '. have increased with time. Thus the evidence from Britain is against the disease being due to a new strain of the agent, but we note that in the United States from 1984 to 1988 outbreaks of scrapie in sheep flocks are reported to have Increased markedly. now being nearly 3 times as high as during any previous period (18).
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. ...
hmmm, this is getting interesting now...
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.
Tuesday, July 29, 2008
Heidenhain Variant Creutzfeldt Jakob Disease Case Report
Heidenhain Variant Creutzfeldt Jakob Disease autopsy case report 'MOM'
DIVISION OF NEUROPATHOLOGY University of Texas Medical Branch 114 McCullough Bldg. Galveston, Texas 77555-0785
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FAX: (409) 772-5315 PHONE: (409) 772-2881
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This document accompanying this transmission contains confidential information belonging to the sender that is legally privileged. This information is intended only for the use of the individual or entry names above. If you are not the intended recipient, you are hereby notified that any disclosure, copying distribution, or the taking of any action in reliances on the contents of this telefaxed information is strictly prohibited. If you received this telefax in error, please notify us by telephone immediately to arrange for return of the original documents. -------------------------- Patient Account: 90000014-518 Med. Rec. No.: (0160)118511Q Patient Name: POULTER, BARBARA Age: 63 YRS DOB: 10/17/34 Sex: F Admitting Race: C
Attending Dr.: Date / Time Admitted : 12/14/97 1228 Copies to:
UTMB University of Texas Medical Branch Galveston, Texas 77555-0543 (409) 772-1238 Fax (409) 772-5683 Pathology Report
FINAL AUTOPSY DIAGNOSIS Autopsy' Office (409)772-2858
Autopsy NO.: AU-97-00435
AUTOPSY INFORMATION: Occupation: Unknown Birthplace: Unknown Residence: Crystal Beach Date/Time of Death: 12/14/97 13:30 Date/Time of Autopsy: 12/15/97 15:00 Pathologist/Resident: Pencil/Fernandez Service: Private Restriction: Brain only
FINAL AUTOPSY DIAGNOSIS
I. Brain: Creutzfeldt-Jakob disease, Heidenhain variant.
snip...see full text ;
Monday, December 14, 2009
Similarities between Forms of Sheep Scrapie and Creutzfeldt-Jakob Disease Are Encoded by Distinct Prion Types
Greetings again Dr. Barron, Dr. Hunter, et al,
I wish to please address a few issues here, and respond a bit if you don't mind, from a LAY person.
WHAT I perceive to be political junk science and regulations there from, by exempting the atypical NOR-98 scrapie from TSE regulations strictly by _assumption_, before transmission studies to assure that transmission cannot accure. This was like putting the cart before the horse, and risk human and animal health around the globe due to this stupid policy.
Monday, November 30, 2009
USDA AND OIE COLLABORATE TO EXCLUDE ATYPICAL SCRAPIE NOR-98 ANIMAL HEALTH CODE
Sunday, March 28, 2010
Nor-98 atypical Scrapie, atypical BSE, spontaneous TSE, trade policy, sound science ?
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.
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 (email@example.com); 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.
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.
Monday, December 1, 2008
When Atypical Scrapie cross species barriers
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.
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.
>>>Sheep scrapie is thought to pose little risk to humans as there have been no documented links between presence of sheep scrapie and the development of human transmissible spongiform encephalopathy (TSE) disease. <<<
I kindly disagree, in my opinion, there is as much evidence for scrapie transmission to humans as there is for the nvCJD from c-BSE to humans, except that there has not been any studies to further prove this. odd how when c-BSE was linked with nvCJD of humans with pathology that is very similar to each other, they confirmed a link between humans. HOWEVER, with the atypical Nor-98 scrapie being very similar to some sub-types of sporadic CJD, and GSS, it's just the opposite, its all spontaneous $$$
(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
Thursday, January 07, 2010
Scrapie and Nor-98 Scrapie November 2009 Monthly Report Fiscal Year 2010 and FISCAL YEAR 2008
Friday, August 27, 2010
NEW ATYPICAL NOR-98 SCRAPIE CASE DETECTED IDAHO NOW 5 CASES DOCUMENTED 2010
Thursday, August 19, 2010
SCRAPIE CANADA UPDATE Current as of 2010-07-31
The following table lists sheep flocks and/or goat herds confirmed to be infected with scrapie in Canada in 2010. Current as of: 2010-07-31
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. ........
1: J Infect Dis 1980 Aug;142(2):205-8
Oral transmission of kuru, Creutzfeldt-Jakob disease, and scrapie to nonhuman primates.
Gibbs CJ Jr, Amyx HL, Bacote A, Masters CL, Gajdusek DC.
Kuru and Creutzfeldt-Jakob disease of humans and scrapie disease of sheep and goats were transmitted to squirrel monkeys (Saimiri sciureus) that were exposed to the infectious agents only by their nonforced consumption of known infectious tissues. The asymptomatic incubation period in the one monkey exposed to the virus of kuru was 36 months; that in the two monkeys exposed to the virus of Creutzfeldt-Jakob disease was 23 and 27 months, respectively; and that in the two monkeys exposed to the virus of scrapie was 25 and 32 months, respectively. Careful physical examination of the buccal cavities of all of the monkeys failed to reveal signs or oral lesions. One additional monkey similarly exposed to kuru has remained asymptomatic during the 39 months that it has been under observation.
The successful transmission of kuru, Creutzfeldt-Jakob disease, and scrapie by natural feeding to squirrel monkeys that we have reported provides further grounds for concern that scrapie-infected meat may occasionally give rise in humans to Creutzfeldt-Jakob disease.
12/10/76 AGRICULTURAL RESEARCH COUNCIL REPORT OF THE ADVISORY COMMITTE ON SCRAPIE Office Note CHAIRMAN: PROFESSOR PETER WILDY
A The Present Position with respect to Scrapie A] The Problem Scrapie is a natural disease of sheep and goats. It is a slow and inexorably progressive degenerative disorder of the nervous system and it ia fatal. It is enzootic in the United Kingdom but not in all countries. The field problem has been reviewed by a MAFF working group (ARC 35/77). It is difficult to assess the incidence in Britain for a variety of reasons but the disease causes serious financial loss; it is estimated that it cost Swaledale breeders alone $l.7 M during the five years 1971-1975. A further inestimable loss arises from the closure of certain export markets, in particular those of the United States, to British sheep. It is clear that scrapie in sheep is important commercially and for that reason alone effective measures to control it should be devised as quickly as possible. Recently the question has again been brought up as to whether scrapie is transmissible to man. This has followed reports that the disease has been transmitted to primates.
One particularly lurid speculation (Gajdusek 1977) conjectures that the agents of scrapie, kuru, Creutzfeldt-Jakob disease and transmissible encephalopathy of mink are varieties of a single "virus". The U.S. Department of Agriculture concluded that it could "no longer justify or permit scrapie-blood line and scrapie-exposed sheep and goats to be processed for human or animal food at slaughter or rendering plants" (ARC 84/77)" The problem is emphasised by the finding that some strains of scrapie produce lesions identical to the once which characterise the human dementias" Whether true or not. the hypothesis that these agents might be transmissible to man raises two considerations. First, the safety of laboratory personnel requires prompt attention. Second, action such as the "scorched meat" policy of USDA makes the solution of the acrapie problem urgent if the sheep industry is not to suffer grievously.
Nature. 1972 Mar 10;236(5341):73-4.
Transmission of scrapie to the cynomolgus monkey (Macaca fascicularis).
Gibbs CJ Jr, Gajdusek DC. Nature 236, 73 - 74 (10 March 1972); doi:10.1038/236073a0
Transmission of Scrapie to the Cynomolgus Monkey (Macaca fascicularis)
C. J. GIBBS jun. & D. C. GAJDUSEK National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, Maryland
SCRAPIE has been transmitted to the cynomolgus, or crab-eating, monkey (Macaca fascicularis) with an incubation period of more than 5 yr from the time of intracerebral inoculation of scrapie-infected mouse brain. The animal developed a chronic central nervous system degeneration, with ataxia, tremor and myoclonus with associated severe scrapie-like pathology of intensive astroglial hypertrophy and proliferation, neuronal vacuolation and status spongiosus of grey matter. The strain of scrapie virus used was the eighth passage in Swiss mice (NIH) of a Compton strain of scrapie obtained as ninth intracerebral passage of the agent in goat brain, from Dr R. L. Chandler (ARC, Compton, Berkshire).
Epidemiology of Scrapie in the United States 1977
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 ...
[Although atypical scrapie is not yet ruled out, it is important to realize this is a type of scrapie that thus far has only tended to appear as a sporadic condition in older animals. Currently it has not been shown to follow the same genetic tendencies for propagation as the usual scrapie. However, the atypical phenotypic appearance has been shown to be preserved on experimental passage. Atypical scrapie was first identified in Norwegian sheep in 1998 and has subsequently been identified in many countries, as Australia may join that list. It is likely that this case will be sent to the UK for definitive conformation. [Ref: M Simmons, T Konold, L Thurston, et al. BMC Veterinary Research 2010, 6:14 [provisional abstract available at
"Background ----------- "Retrospective studies have identified cases predating the initial identification of this form of scrapie, and epidemiological studies have indicated that it does not conform to the behaviour of an infectious disease, giving rise to the hypothesis that it represents spontaneous disease. However, atypical scrapie isolates have been shown to be infectious experimentally, through intracerebral inoculation in transgenic mice and sheep. [Many of the neurological diseases can be transmitted by intracerebral inoculation, which causes this moderator to approach intracerebral studies as a tool for study, but not necessarily as a direct indication of transmissibility of natural diseases. - Mod.TG]
"The 1st successful challenge of a sheep with 'field' atypical scrapie from an homologous donor sheep was reported in 2007.
"Results -------- "This study demonstrates that atypical scrapie has distinct clinical, pathological, and biochemical characteristics which are maintained on transmission and sub-passage, and which are distinct from other strains of transmissible spongiform encephalopathies in the same host genotype.
"Conclusions ------------ Atypical scrapie is consistently transmissible within AHQ homozygous sheep, and the disease phenotype is preserved on sub-passage."
Lastly, this moderator wishes to thank Terry Singletary for some of his behind the scenes work of providing citations and references for this posting. - Mod.TG]
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.
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: firstname.lastname@example.org
Wednesday, March 31, 2010
Atypical BSE in Cattle / position: Post Doctoral Fellow
14th International Congress on Infectious Diseases H-type and L-type Atypical BSE January 2010 (special pre-congress edition)
18.173 page 189
Experimental Challenge of Cattle with H-type and L-type Atypical BSE
A. Buschmann1, U. Ziegler1, M. Keller1, R. Rogers2, B. Hills3, M.H. Groschup1. 1Friedrich-Loeffler-Institut, Greifswald-Insel Riems, Germany, 2Health Canada, Bureau of Microbial Hazards, Health Products & Food Branch, Ottawa, Canada, 3Health Canada, Transmissible Spongiform Encephalopathy Secretariat, Ottawa, Canada
Background: After the detection of two novel BSE forms designated H-type and L-type atypical BSE the question of the pathogenesis and the agent distribution of these two types in cattle was fully open. From initial studies of the brain pathology, it was already known that the anatomical distribution of L-type BSE differs from that of the classical type where the obex region in the brainstem always displays the highest PrPSc concentrations. In contrast in L-type BSE cases, the thalamus and frontal cortex regions showed the highest levels of the pathological prion protein, while the obex region was only weakly involved.
Methods:We performed intracranial inoculations of cattle (five and six per group) using 10%brainstemhomogenates of the two German H- and L-type atypical BSE isolates. The animals were inoculated under narcosis and then kept in a free-ranging stable under appropriate biosafety conditions.At least one animal per group was killed and sectioned in the preclinical stage and the remaining animals were kept until they developed clinical symptoms. The animals were examined for behavioural changes every four weeks throughout the experiment following a protocol that had been established during earlier BSE pathogenesis studies with classical BSE.
Results and Discussion: All animals of both groups developed clinical symptoms and had to be euthanized within 16 months. The clinical picture differed from that of classical BSE, as the earliest signs of illness were loss of body weight and depression. However, the animals later developed hind limb ataxia and hyperesthesia predominantly and the head. Analysis of brain samples from these animals confirmed the BSE infection and the atypical Western blot profile was maintained in all animals. Samples from these animals are now being examined in order to be able to describe the pathogenesis and agent distribution for these novel BSE types. Conclusions: A pilot study using a commercially avaialble BSE rapid test ELISA revealed an essential restriction of PrPSc to the central nervous system for both atypical BSE forms. A much more detailed analysis for PrPSc and infectivity is still ongoing.
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
Bacliff, TX, USA
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.
12 years independent research of available data
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.
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.
page 114 ;
Wednesday, February 24, 2010
Transmissible Spongiform encephalopathy (TSE) animal and human TSE in North America 14th
ICID International Scientific Exchange Brochure -
Atypical BSE, BSE, and other human and animal TSE in North America Update October 19, 2009
I ask Professor Kong ;
Thursday, December 04, 2008 3:37 PM Subject: RE: re--Chronic Wating Disease (CWD) and Bovine Spongiform Encephalopathies (BSE): Public Health Risk Assessment
''IS the h-BSE more virulent than typical BSE as well, or the same as cBSE, or less virulent than cBSE? just curious.....''
Professor Kong reply ;
''As to the H-BSE, we do not have sufficient data to say one way or another, but we have found that H-BSE can infect humans. I hope we could publish these data once the study is complete.
Thanks for your interest.''
Qingzhong Kong, PhD Associate Professor Department of Pathology Case Western Reserve University Cleveland, OH 44106 USA
I look forward to further transmission studies, and a true ENHANCED BSE/atypical BSE surveillance program put forth testing all cattle for human and animal consumption for 5 years. a surveillance program that uses the most sensitive TSE testing, and has the personnel that knows how to use them, and can be trusted. I look forward to a stringent mad cow feed ban being put forth, and then strictly enforced. we need a forced, not voluntary feed ban, an enhanced feed ban at that, especially excluding blood. we need some sort of animal traceability. no more excuses about privacy. if somebody is putting out a product that is killing folks and or has the potential to kill you, then everybody needs to know who they are, and where that product came from. same with hospitals, i think medical incidents in all states should be recorded, and made public, when it comes to something like a potential accidental transmission exposure event. so if someone is out there looking at a place to go have surgery done, if you have several hospitals having these type 'accidental exposure events', than you can go some place else. it only makes sense. somewhere along the road, the consumer lost control, and just had to take whatever they were given, and then charged these astronomical prices. some where along the line the consumer just lost interest, especially on a long incubating disease such as mad cow disease i.e. Transmissible Spongiform Encephalopathy. like i said before, there is much more to the mad cow story than bovines and eating a hamburger, we must start focusing on all TSE in all species. ...TSS
Wednesday, March 31, 2010
Atypical BSE in Cattle
Archive Number 20100405.1091 Published Date 05-APR-2010 Subject PRO/AH/EDR> Prion disease update 1010 (04)
PRION DISEASE UPDATE 2010 (04)
A ProMED-mail post
ProMED-mail is a program of the International Society for Infectious Diseases
Communicated by: Terry S Singeltary Sr
[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
.57 The experiment which might have determined whether BSE and scrapie were caused by the same agent (ie, the feeding of natural scrapie to cattle) was never undertaken in the UK. It was, however, performed in the USA in 1979, when it was shown that cattle inoculated with the scrapie agent endemic in the flock of Suffolk sheep at the United States Department of Agriculture in Mission, Texas, developed a TSE quite unlike BSE. 32 The findings of the initial transmission, though not of the clinical or neurohistological examination, were communicated in October 1988 to Dr Watson, Director of the CVL, following a visit by Dr Wrathall, one of the project leaders in the Pathology Department of the CVL, to the United States Department of Agriculture. 33 The results were not published at this point, since the attempted transmission to mice from the experimental cow brain had been inconclusive. The results of the clinical and histological differences between scrapie-affected sheep and cattle were published in 1995. Similar studies in which cattle were inoculated intracerebrally with scrapie inocula derived from a number of scrapie-affected sheep of different breeds and from different States, were carried out at the US National Animal Disease Centre. 34 The results, published in 1994, showed that this source of scrapie agent, though pathogenic for cattle, did not produce the same clinical signs of brain lesions characteristic of BSE.
32 Clark, W., Hourrigan, J. and Hadlow, W. (1995) Encephalopathy in Cattle Experimentally Infected with the Scrapie Agent, American Journal of Veterinary Research, 56, 606-12
PLEASE NOTE *
Over the next 8-10 weeks, approximately 40% of all the adult mink on the farm died from TME.
The rancher was a ''dead stock'' feeder using mostly (>95%) downer or dead dairy cattle...
In Confidence -
Perceptions of unconventional slow virus diseases of animals in the USA - APRIL-MAY 1989 - G A H Wells
3. Prof. A Robertson gave a brief account of BSE. The US approach was to accord it a very low profile indeed. Dr. A Thiermann showed the picture in the ''Independent'' with cattle being incinerated and thought this was a fanatical incident to be avoided in the US at all costs. BSE was not reported in the USA.
CWD occurred principally in two locations, this one at Sybille and in a similar faccility at Fort Collins, Colorado, some 120 miles southwest. It was estimated that in total probably 60-70 cases of CWD have occurred.
It was difficult to gain a clear account of incidence and temporal sequence of events (-this presumably is data awaiting publication - see below) but during the period 1981-1984, 10-15 cases occurred at the Sybille facility.
The moribidity amongst mule deer in the facilities ie. those of the natural potentially exposed group has been about 90% with 100% mortality.
Spraker suggested an interesting explanation for the occurrence of CWD. The deer pens at the Foot Hills Campus were built some 30-40 years ago by a Dr. Bob Davis. At or abut that time, allegedly, some scrapie work was conducted at this site. When deer were introduced to the pens they occupied ground that had previously been occupied by sheep.
3.57 The experiment which might have determined whether BSE and scrapie were caused by the same agent (ie, the feeding of natural scrapie to cattle) was never undertaken in the UK. It was, however, performed in the USA in 1979, when it was shown that cattle inoculated with the scrapie agent endemic in the flock of Suffolk sheep at the United States Department of Agriculture in Mission, Texas, developed a TSE quite unlike BSE.339 The findings of the initial transmission, though not of the clinical or neurohistological examination, were communicated in October 1988 to Dr Watson, Director of the CVL, following a visit by Dr Wrathall, one of the project leaders in the Pathology Department of the CVL, to the United States Department of Agriculture.340 The results were not published at this point, since the attempted transmission to mice from the experimental cow brain had been inconclusive. The results of the clinical and histological differences between scrapie-affected sheep and cattle were published in 1995. Similar studies in which cattle were inoculated intracerebrally with scrapie inocula derived from a number of scrapie-affected sheep of different breeds and from different States, were carried out at the US National Animal Disease Centre.341 The results, published in 1994, showed that this source of scrapie agent, though pathogenic for cattle,
*** did not produce the same clinical signs of brain lesions characteristic of BSE. ***
3.58 There are several possible reasons why the experiment was not performed in the UK. It had been recommended by Sir Richard Southwood (Chairman of the Working Party on Bovine Spongiform Encephalopathy) in his letter to the Permanent Secretary of MAFF, Mr (now Sir) Derek Andrews, on 21 June 1988,342 though it was not specifically recommended in the Working Party Report or indeed in the Tyrrell Committee Report (details of the Southwood Working Party and the Tyrell Committee can be found in vol. 4: The Southwood Working Party, 1988–89 and vol. 11: Scientists after Southwood respectively). The direct inoculation of scrapie into calves was given low priority, because of its high cost and because it was known that it had already taken place in the USA.343 It was also felt that the results of such an experiment would be hard to interpret. While a negative result 337 Fraser, H., Bruce, M., Chree, A., McConnell, I. and Wells, G. (1992) Transmission of Bovine Spongiform Encephalopathy and Scrapie to Mice, Journal of General Virology, 73, 1891–7; Bruce, M., Chree, A., McConnell, I., Foster, J., Pearson, G. and Fraser, H. (1994) Transmission of Bovine Spongiform Encephalopathy and Scrapie to Mice: Strain Variation and the Species Barrier, Philosophical Transactions of the Royal Society of London, Series B, Biological Sciences, 343, 405–11 338 Bruce, M., Will, R., Ironside, J., McConell, I., Drummond, D., Suttie, A., McCordie, L., Chree, A., Hope, J., Birkett, C., Cousens, S., Fraser, H. and Bostock, C. (1997) Transmissions to Mice Indicate that ‘New Variant’ CJD is Caused by the BSE Agent, Nature, 389, 498–501 339 Clark, W., Hourrigan, J. and Hadlow, W. (1995) Encephalopathy in Cattle Experimentally Infected with the Scrapie Agent, American Journal of Veterinary Research, 56, 606–12 340 YB88/10.00/1.1 341 Cutlip, R., Miller, J., Race, R., Jenny, A., Katz, J., Lehmkuhl, H., Debey, B. and Robinson, M. (1994) Intracerebral Transmission of Scrapie to Cattle, Journal of Infectious Diseases, 169, 814–20 342 YB88/6.21/1.2 343 YB88/11.17/2.4 SCIENCE 84 would be informative, a positive result would need to demonstrate that when scrapie was transmitted to cattle, the disease which developed in cattle was the same as BSE.344 Given the large number of strains of scrapie and the possibility that BSE was one of them, it would be necessary to transmit every scrapie strain to cattle separately, to test the hypothesis properly. Such an experiment would be expensive. Secondly, as measures to control the epidemic took hold, the need for the experiment from the policy viewpoint was not considered so urgent. It was felt that the results would be mainly of academic interest.345 3.59 Nevertheless, from the first demonstration of transmissibility of BSE in 1988, the possibility of differences in the transmission properties of BSE and scrapie was clear. Scrapie was transmissible to hamsters, but by 1988 attempts to transmit BSE to hamsters had failed. Subsequent findings increased that possibility.
Monday, August 9, 2010
National Prion Disease Pathology Surveillance Center Cases Examined (July 31, 2010)
(please watch and listen to the video and the scientist speaking about atypical BSE and sporadic CJD and listen to Professor Aguzzi)
SEE where sporadic cjd in the USA went from 59 cases in 1997, to 216 cases in 2009. a steady increase since 1997. ...TSS
National Prion Disease Pathology Surveillance Center Cases Examined (July 31, 2010)
Year Total Referrals2 Prion Disease Sporadic Familial Iatrogenic vCJD
1997 114 68 59 9 0 0
2009 425 259 216 43 0 0
see full text ;
Wednesday, August 18, 2010
Incidence of CJD Deaths Reported by CJD-SS in Canada as of July 31, 2010
Tuesday, September 14, 2010
Transmissible Spongiform Encephalopathies Advisory Committee; Notice of Meeting October 28 and 29, 2010 (COMMENT SUBMISSION)
Tuesday, September 28, 2010
Variant CJD: where has it gone, or has it?
Pract Neurol 2010; 10: 250–251
Friday, September 24, 2010
USA Blood products, collected from a donor who was at risk for vCJD, were distributed SEPTEMBER 2010
Wednesday, September 08, 2010
Emerging Infectious Diseases: CJD, BSE, SCRAPIE, CWD, PRION, TSE Evaluation to Implementation for Transfusion and Transplantation September 2010
Sunday, April 18, 2010
SCRAPIE AND ATYPICAL SCRAPIE TRANSMISSION STUDIES A REVIEW 2010
Saturday, October 2, 2010
BSE surveillance front and centre: CFIA and USA
UK EXPORTS BEEF VEAL USA , MEXICO $ CANADA ONLY other Countries list in PDF file)
USA -------- TOTALS ''8'' TONS CANADA -- TOTALS ''29'' TONS
1995 UK EXPORT BEEF AND VEAL TO USA AND CANADA
USA ------- TOTALS ''358'' TONS
CANADA --TOTALS ''24'' TONS
BONE-IN BEEF AND VEAL
USA-------- TOTALS ''10'' TONS (i think this is part of the 358 tons above?)
UK EXPORT OF LIKE CATTLE TO USA AND CANADA
1986 TO 1996 USA TOTAL = 1297
1986 TO 1996 CAN TOTAL = 299
UK EXPORT MEAT OR OFFAL OF BOVINE ANIMALS DEC 1987
CANADA -- 64,526 KG
UK EXPORT OFFALS OF BOVINE ANIMALS FRESH CHILLED OR FROZEN OTHER THAN LIVER DEC 1987 YTD
USA -- 45,943 KG
UK EXPORT MEAT OF BOVINE ANIMAL WITH BONE IN 1988
CANADA -- 4,163 KG
PREP OR PRES MEAT OR OFFAL OF BOVINE ANIMALS CUMULATIVE TO DEC 1988
USA -------- 28,609 KG CANADA -- 22,044 KG
MEAT OF BOVINE ANIMALS WITH BONE IN CUMULATIVE TO ANUAL 1989
USA -------- 17,880 KG MEXICO---- 33,444 KG
BONELESS MEAT OF BOVINE 1989
USA --------111,953 KG CANADA---1,800 KG MEXICO --- 1,143,387 KG
EDIBLE OFFAL OF BOVINE ANIMALS 1989
USA -------- 19,980 KG MEXICO--- 31,244 KG
MEAT OF BOVINE ANIMALS BONELESS 1990
UK Exports of Live Cattle by Value 1986-96
USA 697 LIVE CATTLE
CANADA 299 LIVE CATTLE
UK TABLE of Exports of meal of meat and meat offal; greaves 1979 - 1995
USA 24 TONS
CANADA 83 TONS
HOWEVER, my files show 44 tons of greaves for USA. ...TSS
Subject: Re: exports from the U.K. of it's MBM to U.S.???
Date: Tue, 8 Feb 2000 14:03:16 +0000
To: email@example.com (Receipt Notification Requested) (Non Receipt Notification Requested)
Terry Meat and bonemeal is not specifically classified for overseas trade purposes. The nearest equivalent is listed as flours and meals of meat or offals (including tankage), unfit for human consumption; greaves. UK exports of this to the US are listed below:
Data for exports b
etween 1975 and 1979 are not readily available. These can be obtained (at a charge) from data retailers appointed by HM Customs and Excise: BTSL (Tel: 01372 463121) or Abacus (01245 252222).
Best wishes Simon Pearsall Overseas trade statistics Stats (C&F)C
Terry S. Singeltary Sr.
P.O. Box 42
Bacliff, Texas USA 77518