Volume 17, Number 12—December 2011
Research
Isolation of Prion with BSE Properties from Farmed Goat
John Spiropoulos , Richard Lockey, Rosemary E. Sallis, Linda A. Terry, Leigh Thorne, Thomas M. Holder, Katy E. Beck, and Marion M. Simmons
Author affiliations: Animal Health and Veterinary Laboratories Agency, Weybridge, Surrey, UK
Abstract
Transmissible spongiform encephalopathies are fatal neurodegenerative diseases that include variant Creutzfeldt-Jakob disease in humans, scrapie in small ruminants, and bovine spongiform encephalopathy (BSE) in cattle. Scrapie is not considered a public health risk, but BSE has been linked to variant Creutzfeldt-Jakob disease. Small ruminants are susceptible to BSE, and in 2005 BSE was identified in a farmed goat in France. We confirm another BSE case in a goat in which scrapie was originally diagnosed and retrospectively identified as suspected BSE. The prion strain in this case was further characterized by mouse bioassay after extraction from formaldehyde-fixed brain tissue embedded in paraffin blocks. Our data show that BSE can infect small ruminants under natural conditions and could be misdiagnosed as scrapie. Surveillance should continue so that another outbreak of this zoonotic transmissible spongiform encephalopathy can be prevented and public health safeguarded.
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Discussion
We confirmed that the agent responsible for TSE in a UK goat, which was initially reported as scrapie in 1990 and subsequently as suspected BSE in 2006 (16), was a BSE agent. This conclusion was based on bioassay of nervous tissue in mice demonstrating similarities of histopathologic lesions, PrPSc mapping in the brain, and WB of PrPSc with those of mice inoculated with BSE from various ovine, caprine, and bovine sources.
From a method perspective, the data suggest that AR, IP, and LP are not optimal bioassay parameters for differentiating TSE sources during first passage because they represent mean values derived from a group of animals that have been inoculated with a specific source. Therefore, a substantial number of animals must die of clinical TSE for these parameters to be meaningful. This finding is a limiting factor in instances in which TSE is diagnosed in only a few animals because of low titer, restricted permissiveness of specific TSE strains in certain laboratory animals, or both. These limitations can be overcome by application of IHC and WB to differentiate BSE from scrapie confidently in individual mice on first passage. Use of IHC has shown that different PrPSc deposits can be identified, and the distribution of each deposit in the brain can be mapped (22,28,32). This approach generates high-resolution data that appear to be specific to individual TSE strains.
The data show that the TSE agents in this study were not altered by the adverse conditions applied to them during histologic procedures. However, titer may decrease, suggesting that the effect of histologic processing is quantitative not qualitative. Therefore, bioassay is a valid approach for identifying BSE in archived histologic material when other techniques are not applicable, as in the current study. Regarding the suitability of different mouse lines for confirming BSE, our data show that any mouse line in which the agent can propagate sufficiently is suitable. An additional requirement at a practical level is the ability to characterize the agent on first passage. In this respect, use of PrP-a mice is preferable because in addition to AR, IP, histopathologic analysis, and PrPSc patterning, WB can also be applied to diagnose BSE. In contrast, its application in PrP-b mice is less informative (33).
These methods can also be applied to analyze bioassay data derived from validated transgenic mouse lines that offer the advantage of higher AR and decreased IP, provided that appropriate transgenic lines are selected and the TSE source and the donor species under investigation are taken into consideration. In this particular instance, our first choices would have been the use of a mouse line overexpressing a bovine transgene in combination with 1 that overexpresses a caprine transgene. At initiation of the study, an established bovinised line was not available to us, and the data generated from the wild-type mice were considered sufficient to identify unequivocally the agent strain. Caprine transgenic mouse lines are still under development and not characterized or widely available. Instead, we used tg338 mice although they show <100% AR and extended IP when inoculated with BSE (26,27). Our data show that this ovinized line offers a feasible alternative for detecting and differentiating caprine TSEs.
The 2 cases of naturally occurring BSE in small ruminants—the 1 reported here and the 1 identified in France (15)—occurred in different countries, during different time periods, and before strict BSE control measures were fully implemented. Therefore, the most likely origin of these 2 cases would be exposure to BSE-contaminated food supplements. Although in France goats constitute 14.3% of the small ruminant population, in the United Kingdom they account for only 0.3% of small ruminants. It is intriguing, therefore, that the only naturally occurring BSE cases in small ruminants in France and particularly in the United Kingdom were detected in goats and not in sheep, although they have also been exposed to contaminated food supplements. A possible explanation could be that goats are generally managed more intensively than sheep and thus might have been exposed to higher doses of the infectious agent because of the more frequent use of concentrates in intensive dairy farming. Similar observations have been reported in cattle, in which the incidence of BSE was significantly higher in dairy herds and in which management is much more intensive than in beef herds (34). In the United Kingdom, most of the commercial goat herds are kept for milk production in a typically intensive production system, similar to dairy cattle.
The BSE case we have confirmed was 1 of 26 historic goat samples examined in the United Kingdom collected during 1984–2002 (16,17). Since 1993, scrapie in goats has been a notifiable disease in the United Kingdom, and since 2005, samples from all suspected cases of TSE in small ruminants are required to be tested for BSE-like features by using WB (19). No BSE cases have been identified, although an intermediate case in a goat was reported and is under investigation by bioassay for final resolution (35,36). This screening of brain samples from all small ruminant cases offers reassurance that BSE is not present in the contemporary small ruminant population. However, application of WB to sheep experimentally co-infected with BSE and scrapie detected only the scrapie agent (37). Also, in contrast to BSE, where infectivity is mainly confined to the nervous system, in small ruminants the BSE agent is widely distributed in peripheral tissues and can be transmitted horizontally (11,38). Therefore, feed ban measures alone would be inadequate to control a BSE outbreak in small ruminants. Also, it would be impossible to prevent BSE from entering the human food chain through consumption of food products derived from small ruminants.
Because TSEs in goats are still a problem, particularly in Mediterranean countries, our data suggest that extensive surveillance and breeding schemes must remain in place to prevent a BSE outbreak in small ruminants and to safeguard public health. This report also highlights several issues regarding the use of mouse bioassay to identify TSE strains. As governing bodies seek confirmation of equivocal cases that are identified worldwide, they must be aware of the limitations, cost, and timescale demands of confirming such cases.
Dr Spiropoulos is a veterinary researcher at Veterinary Laboratories Agency with a particular interest in animal pathology. He is the head of the Mouse Bioassay Team that specializes in pathology of experimental animals. His research interests include neurodegenerative disorders and animal diseases of policy relevance, particularly zoonoses.
Acknowledgments
We thank John Sheehan for tissue retrieval from wax-impregnated tissue blocks; Angel Ortiz-Pelaez for epidemiologic assistance; histopathology employees at Veterinary Laboratories Agency for expert technical support in histopathology and immunohistochemistry; and Animal Services Unit employees at Veterinary Laboratories Agency for expert support with animal procedures and care.
This work was supported by a Department of Environment, Food and Rural Affairs grant (project SE1849).
http://wwwnc.cdc.gov/eid/article/17/12/11-0333_article.htm
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
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
http://nor-98.blogspot.com/
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
Monday, November 22, 2010
Atypical transmissible spongiform encephalopathies in ruminants: a challenge for disease surveillance and control
REVIEW ARTICLES
http://transmissiblespongiformencephalopathy.blogspot.com/2010/11/atypical-transmissible-spongiform.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
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
Tuesday, February 01, 2011
Sparse PrP-Sc accumulation in the placentas of goats with naturally acquired scrapie
http://scrapie-usa.blogspot.com/2011/02/sparse-prp-sc-accumulation-in-placentas.html
Sheep/Goat milk, scrapie-free and or BSE-free ???
Sheep milk, scrapie-free
When consumers perceive a food as unsafe, demand for the food can drop as in the bovine spongiform encephalopathy (BSE) revelations of the 1990s. A European project, Riskscra, has put together comprehensive guidelines for sheep milk producers and the industry as a whole to offer a scrapie-free assurance for ovine milk products.
Sheep milk production is an important part of the dairy products industry in Mediterranean countries. The dairy sheep industry is based on local breeds adapted to the production methods and environment.
Experimental evidence has indicated that BSE is transmissible from cows to sheep through oral and parenteral (other than through the alimentary canal) means. Abnormal prion proteins (PrPs) have been found in the mammary glands of sheep with mastitis and scrapie. The fear is that the scrapie may actually be BSE.
The genetics of scrapie resistance is known inasmuch as the ARQ/ARQ genotype is susceptible to some forms of scrapie and experimental BSE. Presence of the PrP also determines a sheep's resistance or susceptibility to transmissible spongiform encephalopathies (TSE). Genetic selection is used as the main means of scrapie control in the United Kingdom.
Along with initiatives from European institutions to promote TSE resistance in livestock, the EU-funded project Riskscra aimed to develop tools to assess the risk of scrapie in milk. Guidelines and recommendations can be applied by breeders and the dairy industry.
Suitable genetic analysis methods for routine control purposes were researched and drawn up into document form for dairy technicians. 'Guidelines to set up traceability in cheese making factories with associated scrapie risk level' integrates International Advisory Group (IAG) dairy production rules and regulations on PrP allele profile control. Specific training courses were also held for dairy technicians.
To make sure that the results of relevant research reach all levels in the sheep dairy production industry, Riskscra organised cooperation between all players and coordination of national and European policies. Networking of research teams was actively encouraged, particularly by bringing European small and medium-sized enterprises (SMEs) in contact with research centres. The results of this initiative also promise to establish a border-free zone for research and create more jobs in the research sector.
Guidelines developed by Riskscra can be used to implement safety or commercial strategies from scratch as well as to improve existing control systems. The Riskscra control system is particularly relevant to producers, breeder organisations and other institutions interested in controlling the scrapie risk in sheep dairy products. A prime example of appropriate use is its application to the current milk payment criteria based only on non-scrapie–related criteria such as milk quantity and bacterial content.
Improving the quality of dairy products on the market increases the confidence of consumers and constitutes a basis for fair competition among dairy industries across Europe, again with added benefits for consumers. In addition, it enhances European competitiveness on the global market.
Country: ITALY
Information Source: Result from the EU funded FP6-SME programme
Date: 2011-11-25
Contact Details
BONACINA, Cesare (Dr)
ISTITUTO SPERIMENTALE ITALIANO "LAZZARO SPALLANZANI"
Director
MILANO
ITALY
Offer ID: 7435
http://cordis.europa.eu/fetch?CALLER=MSS_IT_OFFR_EN&ACTION=D&DOC=3&CAT=OFFR&QUERY=0133f09c98dd:2ddc:23d0d437&RCN=7435
TO date, and i imphasize 'to date', there has been no documented evidence of transmission of BSE via milk of BSE infected cow to another cow. however, with the limited testing done to date, on just the c-BSE, you cannot rule this out, especially with the atypical BSE L-type i.e. BASE, being much more virulent. Concern has been increasing due to fluids from TSE species i.e. blood, urine, and milk, and the fact that infectivity has been detected. ...tss
Prion infectivity has now been detected in blood, urine and milk.
please see ;
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
In small ruminants, a new atypical form of scrapie currently represents up to 50% of detected cases and even involves sheep selected for resistance to classical scrapie. The consequences for animal and human health are still unknown and there may be a potential connection with atypical BSE. These atypical scrapie cases constitute a second threat not envisioned previously which could deeply modify the European approach to prion diseases.
Third threat
The species barrier between human and cattle might be weaker than previously expected and the risk of transmission of prion diseases between different species has been notoriously unpredictable. The emergence of new atypical strains in cattle and sheep together with the spread of chronic wasting disease in cervids renders the understanding of the species barrier critical. This constitutes a third threat not properly envisioned previously that could deeply modify the European approach to prion diseases.
Fourth threat
Prion infectivity has now been detected in blood, urine and milk and this has potential consequences on risk assessments for the environment and food as well as for contamination of surfaces including medical instruments. Furthermore the procedures recommended for decontamination of MBM (Meat and Bone Meal), which are based on older methodologies not designed for this purpose, have turned out to be of very limited efficacy and compromise current policies concerning the reuse of these high value protein supplements (cross-contamination of feed circuits are difficult to control). It should be noted that the destruction or very limited use of MBM is estimated to still cost 1 billion euros per year to the European economy,
whereas other countries, including the US,
Brazil, and Argentine do not have these constraints.
However, many uncertainties remain concerning the guarantees that can be reasonably provided for food and feed safety and scientific knowledge about the causative agents (prions) will continue to evolve. This decontamination and environmental issue is a fourth threat that could modify deeply the European approach to prion diseases.
Fifth threat The precise nature of prions remains elusive. Very recent data indicate that abnormal prion protein (PrPTSE) can be generated from the brains of normal animals, and under some conditions (including contaminated waste water) PrPTSE can be destroyed whereas the BSE infectious titre remains almost unchanged, a finding that underlines the possibility of having BSE without any detectable diagnostic marker. These are just two areas of our incomplete knowledge of the fundamental biology of prions which constitute a fifth threat to the European approach to prion diseases.
Sixth threat The absence of common methods and standardisation in the evaluation of multiple in vivo models with different prion strains and different transgenic mice expressing PrP from different species (different genotypes of cattle, sheep, cervids, etc) renders a complete and comprehensive analysis of all the data generated by the different scientific groups almost impossible. This deeply impairs risk assessment. Moreover, the possibility of generating PrPTSE de novo with new powerful techniques has raised serious questions about their appropriateness for use as blood screening tests. The confusion about an incorrect interpretation of positive results obtained by these methods constitutes a sixth threat to European approach to prion diseases.
Seventh Threat The detection of new or re-emerging prion diseases in animals or humans which could lead to a new crisis in consumer confidence over the relaxation of precautionary measures and surveillance programmes constitutes a seventh threat that could modify the European approach to prion diseases.
http://www.neuroprion.org/en/np-neuroprion.html
Goat BSE: Proposal for Improvement of Goat TSE Discriminative Diagnosis and Susceptibility based Assessment of BSE Infectivity in Goat Milk and Meat
Funded by EU, DEFRA This project is run by a consortium of ten research teams in seven EU countries.
In light of the known ability of the BSE agent to cross the animal/human species barrier, recent evidence establishing the presence of BSE in goat is especially alarming, as it represents a new potential risk of food-born contamination to human consumers of goat milk and meat products. The main objective is to determine the tissue distribution of BSE after oral exposure of goats and to do this while simultaneously generating data on genetic susceptibility in the most common used production breeds. This proposal aims at (i) providing data for the evaluation of human risk associated with goat BSE, (ii) providing pathogenesis data and biological material from first and second passage BSE in goats, (iii) evaluating the possibility of BSE self-maintenance in goat herds through maternal or horizontal transmission, (iv) validating and improving our ability to detect caprine BSE and discriminate it from scrapie in goats. Our approach will establish the influence of PrP gene polymorphisms on scrapie and BSE susceptibility so that genetics could potentially be used for the control of field TSE outbreaks in goats. We will also document European field TSE strain variability in goats by recruiting a large number of TSE goat isolates from affected European countries. Already established or specifically created animal models (strain typing) and biochemical tools (PrPSc typing), will be tested for their ability to efficiently discriminate goat BSE/scrapie. Finally, by measuring infectivity in various tissues collected from goats at different stages of BSE infection, we will provide essential data for quantitative risk assessment.
http://www.roslin.ed.ac.uk/wilfred-goldmann/goat-bse:-proposal-for-improvement-of-goat-tse-discriminative-diagnosis-and-susceptibility-based-assessment-of-bse-infectivity-in-goat-milk-and-meat/
Vet. Res. (2010) 41:48 Original article
Pathogenesis of natural goat scrapie: modulation by host PRNP genotype and effect of co-existent conditions
Lorenzo González1*, Stuart Martin1, Stephen A.C. Hawkins2, Wilfred Goldmann3, Martin Jeffrey1 and Sílvia Sisó1
1 Veterinary Laboratories Agency (VLA-Lasswade), Pentlands Science Park, Penicuik, Midlothian EH26 0PZ, United Kingdom 2 VLA-Weybridge, Addlestone, Surrey KT15 3NB, United Kingdom 3 The Roslin Institute and R(D)SVS University of Edinburgh, Roslin, Midlothian EH25 9PS, United Kingdom
* Corresponding author: l.gonzalez@vla.defra.gsi.gov.uk
Received: 13 January 2010 Accepted: 7 April 2010
Abstract
After detection of a high prevalence of scrapie in a large dairy goat herd, 72 infected animals were examined by immunohistochemistry with prion protein (PrP) antibody Bar224 to study the pathogenesis of the infection. Tissues examined included the brain and thoracic spinal cord (TSC), a wide selection of lymphoreticular system (LRS) tissues, the distal ileum and its enteric nervous system (ENS), and other organs, including the mammary gland. The whole open reading frame of the PRNP gene was sequenced and antibodies to caprine arthritis-encephalitis virus (CAEV) infection were determined. Unexpectedly, accumulation of disease-associated PrP (PrPd) in the brain was more frequent in methionine carriers at codon 142 (24/32, 75.0%) than amongst isoleucine homozygotes (14/40, 35.0%). The latter, however, showed significantly greater amounts of brain PrPd than the former (average scores of 9.3 and 3.0, respectively). A significant proportion of the 38 goats that were positive in brain were negative in the ENS (44.7%) or in the TSC (39.5%). These results, together with the early and consistent involvement of the circumventricular organs and the hypothalamus, point towards a significant contribution of the haematogenous route in the process of neuroinvasion. Chronic enteritis was observed in 98 of the 200 goats examined, with no association with either scrapie infection or presence of PrPd in the gut. Lymphoproliferative interstitial mastitis was observed in 13/31 CAEV-positive and scrapie-infected goats; PrPd in the mammary gland was detected in five of those 13 goats, suggesting a possible contribution of CAEV infection in scrapie transmission via milk.
Key words: scrapie / goat / prion neuroinvasion / transmissible spongiform encephalopathy / CAEV
© The British Crown, published by INRA/EDP Sciences, 2010
http://www.vetres.org/index.php?option=com_article&access=standard&Itemid=129&url=/articles/vetres/abs/2010/04/v100001/v100001.html
please see more here ;
http://scrapie-usa.blogspot.com/2010/04/scrapie-and-atypical-scrapie.html
6 January 2010 - The public “TSEs in goats” website Link:
http://www.goatbse.eu/
Since December 2006 a new EU funded project has started that has been essentially developed from NeuroPrion TSEgoat task group members and their progress: “GoatBSE: Proposal for improvement of goat TSE discriminative diagnosis and susceptibility based assessment of BSE infectivity in goat milk and meat.” (European STREP project FOOD-CT-2006-36353, frame work 6, area Thematic priority: Food quality and safety). In this project the focus of study is about consequences of an infection with BSE in goats for disease transmission and product safety.
http://www.neuroprion.org/en/np-news.html
Sheep with Scrapie and Mastitis Transmit Infectious Prions through the Milk?
Ciriaco Ligios1,†, Maria Giovanna Cancedda1, Antonello Carta2, Cinzia Santucciu1, Caterina Maestrale1, Francesca Demontis1, Mariangela Saba1, Cristiana Patta1, James C. DeMartini3, Adriano Aguzzi4,†,* and Christina J. Sigurdson4,5,6,†,*
+ Author Affiliations
1Istituto Zooprofilattico Sperimentale della Sardegna, Sassari, Italy
2Research Unit of Genetics and Biotechnology, DIRPA, AGRIS Sardinia, Olmedo, Italy
3Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, Colorado
4Institute of Neuropathology, UniversitätsSpital Zürich, Zürich, Switzerland
5 Department of Pathology, School of Medicine, University of California, San Diego, California
6Department of Pathology, Microbiology, and Immunology, University of California, Davis, California
Next Section
ABSTRACT
Prions are misfolded proteins that are infectious and naturally transmitted, causing a fatal neurological disease in humans and animals. Prion shedding routes have been shown to be modified by inflammation in excretory organs, such as the kidney. Here, we show that sheep with scrapie and lentiviral mastitis secrete prions into the milk and infect nearly 90% of naïve suckling lambs. Thus, lentiviruses may enhance prion transmission, conceivably sustaining prion infections in flocks for generations. This study also indicates a risk of prion spread to sheep and potentially to other animals through dietary exposure to pooled sheep milk or milk products.
http://jvi.asm.org/content/85/2/1136.long
Commentary
In vitro amplification of prions from milk in the detection of subclinical infections
Volume 3, Issue 4 October/November/December 2009 Pages 236 - 239 http://dx.doi.org/10.4161/pri.3.4.10425
Kevin C. Gough, Claire A. Baker, Maged Taema and Ben C. Maddison
View affiliations
Prions can be amplified by serial protein misfolding cyclic amplification (sPMCA) from the milk of a high proportion of apparently healthy, scrapie exposed sheep with PRNP genotypes not previously associated with high disease penetrance1. These data strongly suggest the widespread presence of subclinical scrapie infections within scrapie-exposed flocks containing sheep with a range of susceptible PRNP genotypes. These data also lead to the hypothesis that similar subclinical disease states may be common for other animal and human prion diseases. Furthermore, the application of sPMCA to milk provides a method to detect such subclinical disease. Here, we describe the high level amplification of bovine spongiform encephalopathy (BSE) prions from both ovine and bovine origin, a methodology that will facilitate the detection of any prions secreted within bovine and ovine milk during subclinical and clinical BSE disease.
http://www.landesbioscience.com/journals/prion/article/10425/?nocache=543132411
Prion Protein in Milk
Nicola Franscini,1 Ahmed El Gedaily,1 Ulrich Matthey,1 Susanne Franitza,1 Man-Sun Sy,2 Alexander Bürkle,3 Martin Groschup,4 Ueli Braun,5 and Ralph Zahn1
Conclusions/Significance
In view of a recent study showing evidence of prion replication occurring in the mammary gland of scrapie infected sheep suffering from mastitis, the appearance of PrPC in milk implies the possibility that milk of TSE-infected animals serves as source for PrPSc.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1762385/
http://www.allprion.com/Documents/Produkteblatt_PrionProtein.pdf
Atypical/Nor98 Scrapie Infectivity in Sheep Peripheral Tissues
Olivier Andréoletti1*, Leonor Orge2, Sylvie L. Benestad3, Vincent Beringue4, Claire Litaise1, Stéphanie Simon5, Annick Le Dur4, Hubert Laude4, Hugh Simmons6, Séverine Lugan1, Fabien Corbière1, Pierrette Costes1, Nathalie Morel5, François Schelcher1, Caroline Lacroux1
Atypical/Nor98 scrapie was first identified in 1998 in Norway. It is now considered as a worldwide disease of small ruminants and currently represents a significant part of the detected transmissible spongiform encephalopathies (TSE) cases in Europe. Atypical/Nor98 scrapie cases were reported in ARR/ARR sheep, which are highly resistant to BSE and other small ruminants TSE agents. The biology and pathogenesis of the Atypical/Nor98 scrapie agent in its natural host is still poorly understood. However, based on the absence of detectable abnormal PrP in peripheral tissues of affected individuals, human and animal exposure risk to this specific TSE agent has been considered low. In this study we demonstrate that infectivity can accumulate, even if no abnormal PrP is detectable, in lymphoid tissues, nerves, and muscles from natural and/or experimental Atypical/Nor98 scrapie cases. Evidence is provided that, in comparison to other TSE agents, samples containing Atypical/Nor98 scrapie infectivity could remain PrPSc negative. This feature will impact detection of Atypical/Nor98 scrapie cases in the field, and highlights the need to review current evaluations of the disease prevalence and potential transmissibility. Finally, an estimate is made of the infectivity loads accumulating in peripheral tissues in both Atypical/Nor98 and classical scrapie cases that currently enter the food chain. The results obtained indicate that dietary exposure risk to small ruminants TSE agents may be higher than commonly believed.
Author Summary
Following the bovine spongiform encephalopathy (BSE) crisis and the identification of its zoonotic properties, a sanitary policy has been implemented based on both eradication of transmissible spongiform encephalopathies (TSE) in food-producing animals and exclusion of known infectious materials from the food chain. Atypical/Nor98 scrapie is a prion disease of small ruminants identified worldwide. Currently it represents a significant part of the TSE cases detected in Europe. The restricted tissue distribution of Atypical/Nor98 scrapie agent in its natural host and the low detected prevalence of secondary cases in affected flocks meant that it is believed to be a poorly transmissible disease. This has led to the view that Atypical/Nor98 scrapie is a spontaneous disorder for which human and animal exposure risk remains low. In this study we demonstrate that in affected individuals, Atypical/Nor98 scrapie agent can disseminate in lymphoid tissues, nerves, and muscles, challenging the idea that it is a brain-restricted infectious agent. Evidence for the deficiencies in the current methods applied for monitoring Atypical/Nor98 scrapie is provided that would indicate an underestimation in the prevalence in the general population and in the affected flocks. These elements challenge the hypothesis on the biology of this recently identified TSE agent.
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Assessing Atypical/Nor98 scrapie transmissibility through oral route in natural host and presence in placenta and in colostrum/milk (which are considered as major sources for TSE transmission between small ruminants) [28], [32] will provide crucial data.
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Citation: Andréoletti O, Orge L, Benestad SL, Beringue V, Litaise C, et al. (2011) Atypical/Nor98 Scrapie Infectivity in Sheep Peripheral Tissues. PLoS Pathog 7(2): e1001285. doi:10.1371/journal.ppat.1001285
Editor: David Westaway, University of Alberta, Canada
Received: June 21, 2010; Accepted: January 10, 2011; Published: February 10, 2011
Copyright: © 2011 Andréoletti 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: The different parts of this work were funded by (i) The Food Standard Agency (UK) M03058, (ii) the FP7 EU project 'Priority' (243950 FP7-KBBE KBBE-2009-1-2-06), and (iii) Programme opérationnel de Coopération territoriale Espagne - France - Andorre 2007-2013 EFA85/08-COTSA. Lymphoid tissue collection in Portuguese sheep was supported by AGROS 558 (PO AGRO 8.1). 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: o.andreoletti@envt.fr
http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1001285
Prions in Milk from Ewes Incubating Natural Scrapie
http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1000238
Friday, February 11, 2011
Atypical/Nor98 Scrapie Infectivity in Sheep Peripheral Tissues
http://nor-98.blogspot.com/2011/02/atypicalnor98-scrapie-infectivity-in.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
12/10/76
AGRICULTURAL RESEARCH COUNCIL REPORT OF THE ADVISORY COMMITTE ON SCRAPIE
Office Note CHAIRMAN: PROFESSOR PETER WILDY
snip...
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.
snip...
76/10.12/4.6
http://web.archive.org/web/20010305223125/www.bseinquiry.gov.uk/files/yb/1976/10/12004001.pdf
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).
http://www.nature.com/nature/journal/v236/n5341/abs/236073a0.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
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
Monday, April 25, 2011
Experimental Oral Transmission of Atypical Scrapie to Sheep
Volume 17, Number 5-May 2011
http://nor-98.blogspot.com/2011/04/experimental-oral-transmission-of.html
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
I strenuously urge the USDA and the OIE et al to revoke the exemption of the legal global trading of atypical Nor-98 scrapie TSE. ...TSS
Friday, February 11, 2011
Atypical/Nor98 Scrapie Infectivity in Sheep Peripheral Tissues
http://nor-98.blogspot.com/2011/02/atypicalnor98-scrapie-infectivity-in.html
Thursday, July 14, 2011
Histopathological Studies of "CH1641-Like" Scrapie Sources Versus Classical Scrapie and BSE Transmitted to Ovine Transgenic Mice (TgOvPrP4)
http://transmissiblespongiformencephalopathy.blogspot.com/2011/07/histopathological-studies-of-ch1641.html
Monday, June 27, 2011
Comparison of Sheep Nor98 with Human Variably Protease-Sensitive Prionopathy and Gerstmann-Sträussler-Scheinker Disease
http://prionopathy.blogspot.com/2011/06/comparison-of-sheep-nor98-with-human.html
BSE: TIME TO TAKE H.B. PARRY SERIOUSLY
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
Thursday, June 2, 2011
USDA scrapie report for April 2011 NEW ATYPICAL NOR-98 SCRAPIE CASES Pennsylvania AND California
http://nor-98.blogspot.com/2011/06/usda-scrapie-report-for-april-2011-new.html
Monday, June 20, 2011 2011
Annual Conference of the National Institute for Animal Agriculture ATYPICAL NOR-98 LIKE SCRAPIE UPDATE USA
http://nor-98.blogspot.com/2011/06/2011-annual-conference-of-national.html
Monday, June 27, 2011
Comparison of Sheep Nor98 with Human Variably Protease-Sensitive Prionopathy and Gerstmann-Sträussler-Scheinker Disease
http://prionopathy.blogspot.com/2011/06/comparison-of-sheep-nor98-with-human.html
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
Case report
Atypical/Nor98 scrapie in the Basque Country: a case report of eight outbreaks
Ana B Rodríguez-Martínez1, Joseba M Garrido1, Sonia Maza1, Leyre Benedicto1, Mariví Geijo1, Nieves Gómez1, Esmeralda Minguijón1, Sylvie L Benestad2 and Ramón A Juste1*
* Corresponding author: Ramón A Juste rjuste@neiker.net
Author Affiliations
1 Department of Animal Health. Neiker-Tecnalia, 48160 Derio. Bizkaia. Spain
2 National Veterinary Institute, Department of Pathology, Postboks 750 Sentrum. 0106 Oslo. Norway
For all author emails, please log on.
BMC Veterinary Research 2010, 6:17 doi:10.1186/1746-6148-6-17
The electronic version of this article is the complete one and can be found online at:
http://www.biomedcentral.com/1746-6148/6/17
Received: 6 November 2009
Accepted: 26 March 2010
Published: 26 March 2010
© 2010 Rodríguez-Martínez 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
Since 2002, an active surveillance program for transmissible spongiform encephalopathy in small ruminants in European Union countries allowed identification of a considerable number of atypical cases with similarities to the previously identified atypical scrapie cases termed Nor98.
Case presentation
Here we report molecular and neuropathological features of eight atypical/Nor98 scrapie cases detected between 2002 and 2009. Significant features of the affected sheep included: their relatively high ages (mean age 7.9 years, range between 4.3 and 12.8), their breed (all Latxa) and their PRNP genotypes (AFRQ/ALRQ, ALRR/ALRQ, AFRQ/AFRQ, AFRQ/AHQ, ALRQ/ALRH, ALRQ/ALRQ). All the sheep were confirmed as atypical scrapie by immunohistochemistry and immunoblotting. Two cases presented more PrP immunolabelling in cerebral cortex than in cerebellum.
Conclusions
This work indicates that atypical scrapie constitutes the most common small ruminant transmissible spongiform encephalopathy form in Latxa sheep in the Spanish Basque Country. Moreover, a new genotype (ALRQ/ALRH) was found associated to atypical scrapie.
SNIP...
Case reports from this study and other case reports from Spain http://www.eeb.es/pags/espana.htm webcite and Portugal [35], indicate a high frequency of atypical cases compared to CS outbreaks in the Iberian Peninsula. It could be speculated that AS/Nor98 is the traditional form of scrapie in the Iberian part of the Basque country, whilst in the French part, the classical form has been predominant [59]. This would point to some unidentified epidemiological features limiting the spread of classical scrapie in the Iberian Peninsula. However, since the analysis of all sheep can not be guaranteed, it is difficult to test this hypothesis. The analysis of all sheep would provide more information about the epidemiology and pathology of this disease. Moreover, it could contribute in assessing whether AS is present in the Basque Country with the same high frequencies as others human TSEs, such as sporadic Creutzfeldt-Jakob disease [60] and Fatal Familiar Insomnia compared to other Spanish autonomous communities (National Epidemiology Centre: http:/ / www.isciii.es/ htdocs/ centros/ epidemiologia/ epidemiologia_listado_ecj.jsp webcite).
SEE FULL TEXT ;
http://www.biomedcentral.com/1746-6148/6/17
Peiffer, J. : Gerstmann-Straussler's disease, atypical multiple sclerosis and carcinomas in a family of sheepbreeders. Acta Neuropath. 56: 87-92, 1982. Peiffer (1982) described a family of sheepbreeders in which a father and 2 sons had GSS. All 3 also had congenital hip dysplasia, as did at least 3 other members of the kindred, all females. Atactic symptoms, dysarthria, and personality changes characterized the clinical course of this disorder, which might be labeled atypical multiple sclerosis. Like CJD , GSS is a form of subacute spongiform encephalopathy. Cases of GSS are clinically similar to the atactic type of CJD. Although there are many neuropathologic similarities, GSS differs from CJD by the presence of kuru-plaques and numerous multicentric, floccular plaques in the cerebral and cerebellar cortex, basal ganglia, and white matter. Whereas only 5 to 15% of CJD cases are familial, most cases of GSS are familial.
http://www.mad-cow.org/Alzheimer_cjd.html
Thursday, June 23, 2011
Experimental H-type bovine spongiform encephalopathy characterized by plaques and glial- and stellate-type prion protein deposits
http://transmissiblespongiformencephalopathy.blogspot.com/2011/06/experimental-h-type-bovine-spongiform.html
Saturday, June 25, 2011
Transmissibility of BSE-L and Cattle-Adapted TME Prion Strain to Cynomolgus Macaque
"BSE-L in North America may have existed for decades"
http://transmissiblespongiformencephalopathy.blogspot.com/2011/06/transmissibility-of-bse-l-and-cattle.html
Sunday, June 26, 2011
Risk Analysis of Low-Dose Prion Exposures in Cynomolgus Macaque
http://transmissiblespongiformencephalopathy.blogspot.com/2011/06/risk-analysis-of-low-dose-prion.html
Wednesday, July 06, 2011
Swine Are Susceptible to Chronic Wasting Disease by Intracerebral Inoculation
(see tonnage of mad cow feed in commerce USA...tss)
http://chronic-wasting-disease.blogspot.com/2011/07/swine-are-susceptible-to-chronic.html
Monday, June 27, 2011
Zoonotic Potential of CWD: Experimental Transmissions to Non-Human Primates
http://chronic-wasting-disease.blogspot.com/2011/06/zoonotic-potential-of-cwd-experimental.html
Transmissible Spongiform encephalopathy (TSE) animal and human TSE in North America
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.
page 114 ;
http://ww2.isid.org/Downloads/14th_ICID_ISE_Abstracts.pdf
International Society for Infectious Diseases Web: http://www.isid.org/
please see full text ;
http://transmissiblespongiformencephalopathy.blogspot.com/
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
Thursday, August 12, 2010
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
Subject: SPONGIFORM ENCEPHALOPATHY ADVISORY COMMITTEE Draft minutes of the 100th meeting held on 25th April 2008
Date: July 13, 2008 at 7:16 pm PST
-------------------- BSE-L@LISTS.AEGEE.ORG --------------------
SPONGIFORM ENCEPHALOPATHY ADVISORY COMMITTEE Draft minutes of the 100th meeting held on 25th April 2008
ITEM 2 - APPROVAL OF MINUTES FROM SEAC 99 (SEAC 100/1) 6. The minutes of SEAC 99 were agreed as a correct record with the following amendment: 4 © SEAC 2008 . Paragraph 7, second bullet point, change ".Institute of Animal Health (IAH)." to ".Roslin Institute (RI)." 7. The committee was updated about transmission studies using isolates from a case of Creutzfeldt-Jakob Disease (CJD)1 which had been discussed at SEAC 99. Two lines of transgenic mice expressing the human prion protein gene homozygous for methionine (MM) or valine (VV) at codon 129 and two lines of conventional mice had been inoculated with isolates from the case. Transmission has been more efficient to the humanised mice compared with the conventional mice. The molecular characteristics of the abnormal prion protein (PrPSc) altered on transmission suggesting the patient may have been infected with an unstable TSE strain. Further work was required to characterise the TSE strain. However, it would be difficult to confirm whether this was related to BSE infection unless additional similar cases arose which could be investigated. 8.
snip...
35. Members asked about the spread of chronic wasting disease (CWD) in the USA. Mr Burke replied that CWD was continuing to spread in the cervid population in the USA.
snip...
One sheep in Cyprus, two in the UK and four from France are under investigation for possible BSE infection. Two further BSE cases were identified with unusual transmission properties in a Defra research project (SE1849) and 5 Countries where cases of BSE in cattle were reported in 2007: UK, Austria, Canada, Czech Republic, France, Germany, Hungary, Ireland, Italy, Japan, Poland, Portugal, Slovenia, Slovakia, Spain and The Netherlands. 6 Countries where atypical scrapie in sheep has been reported since 2002: Belgium, Denmark, the Falkland Islands, Finland, France, Germany, Greece, Hungary, Ireland, Italy, The Netherlands, Norway, Portugal, Slovenia, Spain, Sweden, UK and USA. 13 © SEAC 2008 are also subject to further characterisation. BSE has been confirmed in one French goat slaughtered in 2002. A UK goat which was originally diagnosed as a case of scrapie in 1990 is under investigation for possible BSE infection. 37.
snip...
40. Members agreed that the statement should not focus entirely on the risk from BSE. A paragraph should be included to describe the risk that a new zoonotic TSE strain might emerge as a result of the relaxations to TSE controls. The possibility that the transmissibility to humans of such a new strain could be much greater than that of BSE should be acknowledged.
http://www.seac.gov.uk/minutes/final100.pdf
SPONGIFORM ENCEPHALOPATHY ADVISORY COMMITTEE Minutes of the 99th meeting held on 14th December 2007
snip...
ITEM 8 - PUBLIC QUESTION AND ANSWER SESSION 40. The Chair explained that the purpose of the question and answer session was to give members of the public an opportunity to ask questions related to the work of SEAC. Mr Terry Singeltary (Texas, USA) had submitted a question prior to the meeting, asking: "With the Nor-98 now documented in five different states so far in the USA in 2007, and with the two atypical BSE H-base cases in Texas and Alabama, with both scrapie and chronic 14 © SEAC 2007 wasting disease (CWD) running rampant in the USA, is there any concern from SEAC with the rise of sporadic CJD in the USA from ''unknown phenotype'', and what concerns if any, in relations to blood donations, surgery, optical, and dental treatment, do you have with these unknown atypical phenotypes in both humans and animals in the USA? Does it concern SEAC, or is it of no concern to SEAC? Should it concern USA animal and human health officials?" 41.
A member considered that this question appeared to be primarily related to possible links between animal and human TSEs in the USA.
There is no evidence that sCJD is increasing in the USA and no evidence of any direct link between TSEs and CJD in the USA. Current evidence does not suggest that CWD is a significant risk to human health. There are unpublished data from a case of human TSE in the USA that are suggestive of an apparently novel form of prion disease with distinct molecular characteristics. However, it is unclear whether the case had been further characterised, if it could be linked to animal TSEs or if other similar cases had been found in the USA or elsewhere. In relation to the possible public health implications of atypical scrapie, H-type BSE and CWD, research was being conducted to investigate possible links and surveillance was in place to detect any changes in human TSEs. Although possible links between these diseases and human TSEs are of concern and require research, there is no evidence to suggest immediate public health action is warranted. The possible human health risks from classical scrapie had been discussed earlier in the meeting. Members noted that there are effective channels of discussion and collaboration on research between USA and European groups. Members agreed it is important to keep a watching brief on new developments on TSEs.
snip...
http://www.seac.gov.uk/minutes/99.pdf
Monday, October 10, 2011
EFSA Journal 2011 The European Response to BSE: A Success Story
snip...
EFSA and the European Centre for Disease Prevention and Control (ECDC) recently delivered a scientific opinion on any possible epidemiological or molecular association between TSEs in animals and humans (EFSA Panel on Biological Hazards (BIOHAZ) and ECDC, 2011). This opinion confirmed Classical BSE prions as the only TSE agents demonstrated to be zoonotic so far but the possibility that a small proportion of human cases so far classified as "sporadic" CJD are of zoonotic origin could not be excluded. Moreover, transmission experiments to non-human primates suggest that some TSE agents in addition to Classical BSE prions in cattle (namely L-type Atypical BSE, Classical BSE in sheep, transmissible mink encephalopathy (TME) and chronic wasting disease (CWD) agents) might have zoonotic potential.
snip...
http://www.efsa.europa.eu/en/efsajournal/pub/e991.htm?emt=1
http://www.efsa.europa.eu/en/efsajournal/doc/e991.pdf
see follow-up here about North America BSE Mad Cow TSE prion risk factors, and the ever emerging strains of Transmissible Spongiform Encephalopathy in many species here in the USA, including humans ;
http://transmissiblespongiformencephalopathy.blogspot.com/2011/10/efsa-journal-2011-european-response-to.html
Thursday, August 4, 2011
Terry Singeltary Sr. on the Creutzfeldt-Jakob Disease Public Health Crisis, Date aired: 27 Jun 2011
(SEE VIDEO)
http://transmissiblespongiformencephalopathy.blogspot.com/2011/08/terry-singeltary-sr-on-creutzfeldt.html
Sunday, August 21, 2011
The British disease, or a disease gone global, The TSE Prion Disease
(SEE VIDEO)
http://transmissiblespongiformencephalopathy.blogspot.com/2011/08/british-disease-or-disease-gone-global.html
Saturday, March 5, 2011
MAD COW ATYPICAL CJD PRION TSE CASES WITH CLASSIFICATIONS PENDING ON THE RISE IN NORTH AMERICA
http://transmissiblespongiformencephalopathy.blogspot.com/2011/03/mad-cow-atypical-cjd-prion-tse-cases.html
http://transmissiblespongiformencephalopathy.blogspot.com/
price of TSE prion poker goes up again $$$
TSS
Saturday, December 3, 2011
Saturday, November 19, 2011
Novel Prion Protein in BSE-affected Cattle, Switzerland
DOI: http://dx.doi.org/10.3201/eid1801.111225 Suggested citation for this article: Seuberlich T, Gsponer M, Drögemüller C, Polak MP, McCutcheon S, Heim D, et al. Novel prion protein in BSE-affected cattle, Switzerland. Emerg Infect Dis. 2012 Jan; [Epub ahead of print]
Novel Prion Protein in BSE-affected Cattle, Switzerland
To the Editor:
Bovine spongiform encephalopathy (BSE) is a feed-borne prion disease that affects mainly cattle but also other ruminants, felids, and humans (1). Currently, 3 types of BSE have been distinguished by Western immunoblot on the basis of the signature of the proteinase K–resistant fragment of the pathologic prion protein (PrPres): the classic type of BSE (C-BSE) and 2 so-called atypical types of BSE with higher or lower molecular masses of PrPres (H-BSE and L-BSE, respectively) (2). C-BSE is transmitted to cattle by ingestion of contaminated meat-and-bone meal, a feed supplement produced from animal carcasses and by-products. H-BSE and L-BSE have been identified by active disease surveillance, and incidence in aged cattle is low; but little is known about their epidemiology, pathobiology, and zoonotic potential (3). We describe 2 recent cases of BSE in aged cattle in Switzerland in which a PrPres phenotype distinct from those of C-, L- and H-BSE was unexpectedly displayed.
In April 2011, an 8-year-old cow (cow 1) died of accidental injury, with no apparent precedent clinical signs, on a farm in the canton of St. Gallen, Switzerland. In the context of active surveillance for BSE, the medulla oblongata was tested and found to be BSE positive by using the PrioStrip test (Prionics AG, Schlieren, Switzerland), a lateral-flow immunochromatographic assay for detection of PrPres. One month later, another cow (cow 2), 15 years of age, in the canton of Berne, Switzerland, was slaughtered because of a hind limb fracture. Information on this animal’s health status before death was unavailable. Statutory testing of the medulla oblongata gave a BSE-positive result by using the Prionics Check Western, a rapid Western blot technique (4). Medulla oblongata samples from the 2 animals were forwarded to the National Reference Laboratory for confirmatory testing.
In accordance with the guidelines of the World Organisation for Animal Health (5), BSE was confirmed for each animal by positive test results in independent, approved screening tests, of which 1 must be a Western blot (online Technical Appendix, wwwnc.cdc.gov/EID/pdfs/11-1225-Techapp.pdf). Because the tissues were severely autolyzed, target structures for the diagnosis of BSE could not be identified, and histopathologic and immunohistochemical results were inconclusive.
The Prionics Western blot detected a similar 3-band PrPres glycoprofile with molecular masses of roughly 16, 20, and 25 kDa for each animal, lower than equivalent PrP protein bands detected in animals with C-BSE (Figure). Sequencing of the open reading frame of the PRNP gene of cow 2 (which was unsuccessful for cow 1) indicated that the encoded protein was identical to the common bovine PrP amino acid sequence (as translated from GenBank accession no. AJ298878) and therefore was not likely to account for the differences observed by Western blot testing.
We next investigated which region of the prion protein was present in these abberant PrPres fragments by probing with a panel of antibodies in the Western blot that bind to different regions of the prion protein (online Technical Appendix). PrPres in cows 1 and 2 was readily detected by antibodies Sha31, 94B4, and JB10. By contrast, antibody 9A2, which maps to the PrPres N terminus, bound only to PrPres in samples from animals with C-, L- and H- BSE but not in samples from cows 1 and 2. The molecular masses of the PrPres moieties from the 2 cows were also clearly distinct from those from controls with L- and H-BSE (Figure). For samples from animals with H-BSE, enzymatic deglycosylation demonstrated PrPres subtypes, 1 and 2, the latter being a C-terminal PrPres fragment of 12–14 kDa (6). To investigate whether the novel PrPres type corresponds to PrPres subtype 2, we compared samples from cow 2 with those from the H-BSE control by Western blot. The PrPres type from the 2 cows reported here and PrPres subtype 2 from the H-BSE control were indeed distinct (Figure).
We report a novel PrPres signature in 2 cows with BSE diagnoses determined according to established criteria. Combining Western blot analysis with an epitope mapping strategy, we ascertained that these animals displayed an N terminally truncated PrPres different from currently classified BSE prions (Figure). The interpretation of these findings remains difficult because neuropathologic and systematic clinical data for the 2 cases are not available. Moreover, the tissue samples were autolyzed, and the question of whether this affected the PrPres molecular signature is of concern. Nonetheless, our findings raise the possibility that these cattle were affected by a prion disease not previously encountered and distinct from the known types of BSE. To confirm this possibility and to assess a potential effect on disease control and public health, in vivo transmission studies using transgenic mouse models and cattle are ongoing. Until results of these studies are available, molecular diagnostic techniques should be used so that such cases are not missed.
Acknowledgments
We thank the BSE screening laboratories at the Center of Laboratory Medicine (ZLM, St. Gallen, Switzerland), Prionics AG, and the veterinary services of the cantons of St. Gallen and Berne for their support. We also thank Jan P.M. Langeveld for kindly providing antibodies 9A2 and 94B4.
This work was financed with resources provided by the Swiss Federal Veterinary Office.
Torsten Seuberlich, Michaela Gsponer, Cord Drögemüller, Miroslaw P. Polak, Sandra McCutcheon, Dagmar Heim, Anna Oevermann, and Andreas Zurbriggen
Author affiliations: University of Berne, Berne, Switzerland (T. Seuberlich, M. Gsponer, C. Drögemüller, A. Oevermann, A. Zurbriggen); National Veterinary Research Institute, Pulawy, Poland (M.P. Polak); University of Edinburgh, Edinburgh, Scotland, UK (S. McCutcheon); and Federal Veterinary Office, Liebefeld, Switzerland (Dagmar Heim)
References
snip...full text ;
http://wwwnc.cdc.gov/eid/pdfs/11-1225-ahead_of_print.pdf?source=govdelivery
=========UPDATE DECEMBER 16, 2011========
=======END UPDATE DECEMBER 16, 2011=============
P.4.23
Transmission of atypical BSE in humanized mouse models
Liuting Qing1, Wenquan Zou1, Cristina Casalone2, Martin Groschup3, Miroslaw Polak4, Maria Caramelli2, Pierluigi Gambetti1, Juergen Richt5, Qingzhong Kong1 1Case Western Reserve University, USA; 2Instituto Zooprofilattico Sperimentale, Italy; 3Friedrich-Loeffler-Institut, Germany; 4National Veterinary Research Institute, Poland; 5Kansas State University (Previously at USDA National Animal Disease Center), USA
Background: 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). Atypical BSE cases have been discovered in three continents since 2004; they include the L-type (also named BASE), the H-type, and the first reported case of naturally occurring BSE with mutated bovine PRNP (termed BSE-M). The public health risks posed by atypical BSE were largely undefined.
Objectives: To investigate these atypical BSE types in terms of their transmissibility and phenotypes in humanized mice. Methods: Transgenic mice expressing human PrP were inoculated with several classical (C-type) and atypical (L-, H-, or Mtype) BSE isolates, and the transmission rate, incubation time, characteristics and distribution of PrPSc, symptoms, and histopathology were or will be examined and compared.
Results: Sixty percent of BASE-inoculated humanized mice became infected with minimal spongiosis and an average incubation time of 20-22 months, whereas only one of the C-type BSE-inoculated mice developed prion disease after more than 2 years. Protease-resistant PrPSc in BASE-infected humanized Tg mouse brains was biochemically different from bovine BASE or sCJD. PrPSc was also detected in the spleen of 22% of BASE-infected humanized mice, but not in those infected with sCJD. Secondary transmission of BASE in the humanized mice led to a small reduction in incubation time.*** The atypical BSE-H strain is also transmissible with distinct phenotypes in the humanized mice, but no BSE-M transmission has been observed so far.
Discussion: Our results demonstrate that BASE is more virulent than classical BSE, has a lymphotropic phenotype, and displays a modest transmission barrier in our humanized mice. BSE-H is also transmissible in our humanized Tg mice. The possibility of more than two atypical BSE strains will be discussed.
Supported by NINDS NS052319, NIA AG14359, and NIH AI 77774.
http://www.prion2009.com/sites/default/files/Prion2009_Book_of_Abstracts.pdf
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
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 ;
.....snip
''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.''
Best regards, Qingzhong Kong, PhD Associate Professor Department of Pathology Case Western Reserve University Cleveland, OH 44106 USA
END...TSS
Thursday, December 04, 2008 2:37 PM
"we have found that H-BSE can infect humans."
personal communication with Professor Kong. ...TSS
BSE-H is also transmissible in our humanized Tg mice.
The possibility of more than two atypical BSE strains will be discussed.
Supported by NINDS NS052319, NIA AG14359, and NIH AI 77774.
http://www.prion2009.com/sites/default/files/Prion2009_Book_of_Abstracts.pdf
http://transmissiblespongiformencephalopathy.blogspot.com/2011/06/experimental-h-type-bovine-spongiform.html
=====================
"The origin of atypical BSE is not yet determined. According to EFSA's scientific opinion published in 2008, all the cases of atypical BSE were reported with birth dates before the real feed ban in January 2001 in Europe. Therefore, the possibility of those atypical cases attributing to the contaminated feeds, just as in classical BSE, cannot be completely denied."
=====================
atypical BSE TSE cases have been around for a long long time, so yes indeed MBM or SRM could very well and most likely did contain atypical TSE of all strains in the USA, and the typical strains as well, of all species. the North America and the USA has typical and atypical BSE, typical and atypical Scrapie, and two strains now of Chronic Wasting Disease, call them typical and atypical, or call them what you want, all this has been rendered and fed to food producing livestock for humans and animals for years in the USA. these are the facts, like them or not. please see ;
1992
IN CONFIDENCE
BSE - ATYPICAL LESION DISTRIBUTION (RBSE 92-21367)
http://tna.europarchive.org/20080609145105/http://www.bseinquiry.gov.uk/files/yb/1993/03/14001001.pdf
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 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://collections.europarchive.org/tna/20090114131343/http://www.bseinquiry.gov.uk/files/yb/1992/10/26001001.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
''THE LINE TO TAKE'' ON IBNC $$$ 1995 $$$
1995
page 9 of 14 ;
30. The Committee noted that the results were unusual. the questioned whether there could be coincidental BSE infection or contamination with scrapie. Dr. Tyrell noted that the feeling of the committee was that this did not represent a new agent but it was important to be prepared to say something publicly about these findings. A suggested line to take was that these were scientifically unpublishable results but in line with the policy of openness they would be made publicly available and further work done to test their validity. Since the BSE precautions were applied to IBNC cases, human health was protected. Further investigations should be carried out on isolations from brains of IBNC cases with removal of the brain and subsequent handling under strict conditions to avoid the risk of any contamination.
31. Mr. Bradley informed the Committee that the CVO had informed the CMO about the IBNC results and the transmission from retina and he, like the Committee was satisfied that the controls already in place or proposed were adequate. ...
snip... see full text
http://collections.europarchive.org/tna/20080102204938/http://www.bseinquiry.gov.uk/files/yb/1995/06/21005001.pdf
http://web.archive.org/web/20030327015011/http://www.bseinquiry.gov.uk/files/yb/1995/06/21005001.pdf
NOW, what about the 'obex only' mode of testing used by the USDA et al for TSE, prions $$$ works for them too, a sure fire way NOT TO FIND MAD COW DISEASE $$$
NOW, read the following please, and then ask yourself, WHY the USDA et al were ONLY TESTING THE OBEX PART OF THE BRAIN in USA cattle for BSE $$$
BECAUSE they knew that would be the least likely way to find BSE/TSE in USA cattle $$$...TSS
Tuesday, November 02, 2010
IN CONFIDENCE
The information contained herein should not be disseminated further except on the basis of "NEED TO KNOW".
BSE - ATYPICAL LESION DISTRIBUTION (RBSE 92-21367) statutory (obex only) diagnostic criteria CVL 1992
http://bse-atypical.blogspot.com/2010/11/bse-atypical-lesion-distribution-rbse.html
1979
In May, 1990 (J/AVMA/196/1679) a paper was published in the Journal of the American Veterinary Medical Association detailing work on the transmission of scrapie to cattle initiated by the USDA at Mission, Texas, in January, 1979. In this study, ten calves were each challenged intracerebrally, orally, intramuscularly and subcutaneously with scrapie which had been subpassaged in either a sheep or a goat.Three of these animals went on to develop clinical symptoms of a spongiform encephalopathy which differed from those seen with BSE infection. PrP was detected in tissues from these cattle, but neurohistologically the changes seen in the brains from these cattle were consistent with scrapie and differed from BSE. Material from the affected cattle was bioassayed in mice which were observed for 2 years. The mice remained clinically and neurohistologically negative *** apart from one group which,although they showed CNS signs, were histologically negative.
http://www.bseinquiry.gov.uk/files/ws/s100bxii.pdf
http://74.125.47.132/search?q=cache:Geyf-zmNTSkJ:www.bseinquiry.gov.uk/files/ws/s100bxii.pdf+mission+texas+bse+inquiry+yb&cd=1&hl=en&ct=clnk&gl=us
3.56 A further difference in the transmission properties of the two diseases was the pattern of disease caused in the brains of experimental animals. Mice inoculated with scrapie material from geographically and temporally distinct sources were found to have variable brain lesions, whereas mice inoculated with BSE material similarly derived from different sources all had very similar patterns of disease. 30 These results showed that, unlike scrapie, only one strain of BSE was present in the inocula derived from different sources. As the current hypothesis suggested that scrapie had transmitted to cattle at a number of geographically separate sites, it might have been expected that several strains of BSE would have been evident, given that over 20 strains of scrapie were known. Since 1996, strain-typing studies in mice have shown that the lesion profile produced by BSE is different to all known scrapie strains. 31
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. 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.
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, 35 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. 36 It was also felt that the results of such an experiment would be hard to interpret. While a negative result 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. 37 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. 38
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.
http://web.archive.org/web/20010224062436/http://www.bseinquiry.gov.uk/report/volume2/chaptea3.htm#820550
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
http://www.bseinquiry.gov.uk/files/yb/1988/10/00001001.pdf
http://www.bseinquiry.gov.uk/report/volume2/chaptea3.htm#820546
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.
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, 35 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. 36 It was also felt that the results of such an experiment would be hard to interpret. While a negative result 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. 37 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. 38
http://www.bseinquiry.gov.uk/report/volume2/chaptea3.htm#820550
http://www.bseinquiry.gov.uk/report/volume2/chaptea3.htm
Saturday, June 25, 2011
Transmissibility of BSE-L and Cattle-Adapted TME Prion Strain to Cynomolgus Macaque
"BSE-L in North America may have existed for decades"
http://transmissiblespongiformencephalopathy.blogspot.com/2011/06/transmissibility-of-bse-l-and-cattle.html
EFSA Journal 2011 The European Response to BSE: A Success Story
This is an interesting editorial about the Mad Cow Disease debacle, and it's ramifications that will continue to play out for decades to come ;
Monday, October 10, 2011
EFSA Journal 2011 The European Response to BSE: A Success Story
snip...
EFSA and the European Centre for Disease Prevention and Control (ECDC) recently delivered a scientific opinion on any possible epidemiological or molecular association between TSEs in animals and humans (EFSA Panel on Biological Hazards (BIOHAZ) and ECDC, 2011). This opinion confirmed Classical BSE prions as the only TSE agents demonstrated to be zoonotic so far but the possibility that a small proportion of human cases so far classified as "sporadic" CJD are of zoonotic origin could not be excluded. Moreover, transmission experiments to non-human primates suggest that some TSE agents in addition to Classical BSE prions in cattle (namely L-type Atypical BSE, Classical BSE in sheep, transmissible mink encephalopathy (TME) and chronic wasting disease (CWD) agents) might have zoonotic potential.
snip...
http://www.efsa.europa.eu/en/efsajournal/pub/e991.htm?emt=1
http://www.efsa.europa.eu/en/efsajournal/doc/e991.pdf
see follow-up here about North America BSE Mad Cow TSE prion risk factors, and the ever emerging strains of Transmissible Spongiform Encephalopathy in many species here in the USA, including humans ;
http://transmissiblespongiformencephalopathy.blogspot.com/2011/10/efsa-journal-2011-european-response-to.html
Wednesday, March 31, 2010
Atypical BSE in Cattle
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.
http://www.prionetcanada.ca/detail.aspx?menu=5&dt=293380&app=93&cat1=387&tp=20&lk=no&cat2
Thursday, August 12, 2010
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
Rural and Regional Affairs and Transport References Committee
The possible impacts and consequences for public health, trade and agriculture of the Government's decision to relax import restrictions on beef Final report June 2010
2.66 Dr Fahey also told the committee that in the last two years a link has been established between forms of atypical CJD and atypical BSE. Dr Fahey said that: They now believe that those atypical BSEs overseas are in fact causing sporadic Creutzfeldt-Jakob disease. They were not sure if it was due to mad sheep disease or a different form. If you look in the textbooks it looks like this is just arising by itself. But in my research I have a summary of a document which states that there has never been any proof that sporadic Creutzfeldt-Jakob disease has arisen de novo-has arisen of itself. There is no proof of that. The recent research is that in fact it is due to atypical forms of mad cow disease which have been found across Europe, have been found in America and have been found in Asia. These atypical forms of mad cow disease typically have even longer incubation periods than the classical mad cow disease.50
http://www.aph.gov.au/senate/committee/rrat_ctte/mad_cows/report/report.pdf
And last but not least, similarities of PrPres between Htype BSE and human prion diseases like CJD or GSS have been put forward [10], as well as between L-type BSE and CJD [17]. These findings raise questions about the origin and inter species transmission of these prion diseases that were discovered through the BSE active surveillance.
full text 18 pages ;
http://www.vetres.org/index.php?option=article&access=standard&Itemid=129&url=/articles/vetres/pdf/2008/04/v07232.pdf
please see full text ;
http://bse-atypical.blogspot.com/2008/06/review-on-epidemiology-and-dynamics-of.html
[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.
http://whqlibdoc.who.int/publications/2003/9241545887.pdf
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/direct.php?id=20100405.1091
CJD RISING SWITZERLAND
CJD is a predominantly sporadic disorder but can also occur as a dominantly inherited or infective condition. Only one of the 26 most recent confirmed cases was identified as carrying a disease related mutation of the PRNP gene, none had identifiable iatrogenic exposure, and none resembled variant CJD. Thus 25 of the 26 cases appear to be sporadic cases. Sporadic CJD is distributed worldwide with a reported incidence of about one in a million per year. Raised awareness of the disease in recent years could account for an increase in reported cases of CJD, although neither an increase in the average age of patients nor more frequent recognition of CJD amongst residents of nursing homes (where dementing illness is prevalent and misdiagnosis might be expected) were seen in the Swiss cases. Moreover, improved ascertainment as an explanation for the observed increase would imply levels of under-reporting in countries other than Switzerland, which appear implausible. The authors of the Lancet report suggest that the rise in cases might be due to some form of unidentified iatrogenic transmission or to exposure to a zoonotic source of infection, though cases do not resemble variant Creutzfeldt-Jakob disease (vCJD). The ongoing surveillance of CJD in Switzerland and the rest of Europe is essential to monitor the situation to see if this rise is sustained in Switzerland, and if a similar rise occurs in other countries (see http://www.eurocjd.ed.ac.uk).
http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=1921
Prion data suggest BSE link to sporadic CJD Declan Butler
Predicting the number of cases of Creutzfeldt-Jakob disease (CJD) in people as a result of transmission of bovine spongiform encephalopathy (BSE) has just got more difficult.Whereas it was thought that BSE only caused a new form of the disease called variant CJD (vCJD), a study in mice from a team led by John Collinge at University College London suggests that it may also cause a disease indistinguishable from the commonest form of classical, or 'sporadic', CJD (E.
http://www.nature.com/nature/journal/v420/n6915/full/420450a.html
Switzerland sporadic CJD ;
Swiss rise in CJD raises concerns over possible BSE link [LONDON] THE LANCET
Plaque attack: Swiss patients have spongiform patterns in the brain typical of sporadic CJD. The number of people dying from Creutzfeldt-Jakob disease (CJD) has risen sharply in Switzerland -- sparking fears of a possible link with bovine spongiform encephalopathy (BSE).
BSE is thought to be the cause of a distinctive form of the brain-wasting disease known as variant CJD. The Swiss cases, in contrast, are standard 'sporadic' CJD. Each year between 1997 and 2000, no more than 11 Swiss people developed CJD. But 19 cases were reported in 2001, and seven were recorded in the first quarter of this year. This is some four times higher than the incidence elsewhere, reports a team led by Adriano Aguzzi of the University Hospital Zurich (M. Glatzel et al. Lancet 360, 139-141; 2002).
The increase could be a mere statistical blip, or it may be due to increased awareness of the disease leading to more diagnoses. More disturbing is the possibility that the cases are linked to the consumption of BSE-infected meat products -- which would mean that the BSE agent can cause two distinct forms of CJD.
Possible links between the Swiss CJD cases and BSE will now be explored by strain-typing experiments in which the disease is transmitted to mice. These tests will take at least a year to complete. "It's the best way to establish or exclude any suspected link," says Moira Bruce of the UK Institute for Animal Health's Neuropathogenesis Unit in Edinburgh.
======================================
Experiences in England and Switzerland -- two countries that discovered mad cow disease in their cattle -- have heightened concerns about the possibility some cases of sporadic CJD are due to consuming mad-cow-tainted beef. Both countries have reported increases in sporadic CJD since mad cow was first detected in British herds in 1986.
Switzerland discovered last year its CJD rate was twice that of any other country in the world. Switzerland had been seeing about eight to 11 cases per year from 1997 to 2000. Then the incidence more than doubled, to 19 cases in 2001 and 18 cases in 2002.
http://www.upi.com/view.cfm?StoryID=20030721-102924-4786r
Mouse model sheds new light on human prion disease
snip...
Professor John Collinge said We are not saying that all or even most cases of sporadic CJD are as a result of BSE exposure, but some more recent cases may be the incidence of sporadic CJD has shown an upward trend in the UK over the last decade. While most of this apparent increase may be because doctors are now more aware of CJD and better at diagnosing it, serious consideration should be given to a proportion of this rise being BSE-related. Switzerland, which has had a substantial BSE epidemic, has noted a sharp recent increase in sporadic CJD.
snip...
http://www.mrc.ac.uk/txt/index/public-interest/public-news-4/public-news_archive/public-news-archive_nov_dec_02/public-bse_and_sporadic_cjd.htm
please see ;
http://creutzfeldt-jakob-disease.blogspot.com/2011/04/sporadic-cjd-rising-text-and-figures-of.html
DR. Adriano Agutzy is one of the world's experts on prion diseases. He says he has ruled out most of the other explanations, and now his main working hypothesis is that at least some Sporadic C.J.D. in Switzerland could be another form of human Mad Cow Disease.
ADRIANO AGUTZY (SCIENTIST):
But this by no means excludes that B.S.E. may manifest itself in humans with different characteristics, and maybe B.S.E. in Switzerland is also different from B.S.E. in the U.K., and then variant C.J.D. will also be different. So I think from the U.K. experience, it's impossible to draw the conclusion that B.S.E. will only give rise to what we know as variant C.J.D.
http://creutzfeldt-jakob-disease.blogspot.com/2009/07/usa-hiding-mad-cow-disease-victims-as.html
please see ;
http://creutzfeldt-jakob-disease.blogspot.com/2011/02/imported-cow-from-switzerland-aged-over.html
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.
http://www.prionetcanada.ca/detail.aspx?menu=5&dt=293380&app=93&cat1=387&tp=20&lk=no&cat2
Tuesday, July 14, 2009
U.S. Emergency Bovine Spongiform Encephalopathy Response Plan Summary and BSE Red Book Date: February 14, 2000 at 8:56 am PST
WHERE did we go wrong $$$
http://madcowtesting.blogspot.com/2009/07/us-emergency-bovine-spongiform.html
SEE FULL TEXT OF ALL THIS HERE ;
2009 UPDATE ON ALABAMA AND TEXAS MAD COWS 2005 and 2006
http://bse-atypical.blogspot.com/2006/08/bse-atypical-texas-and-alabama-update.html
Thursday, June 23, 2011
Experimental H-type bovine spongiform encephalopathy characterized by plaques and glial- and stellate-type prion protein deposits
http://transmissiblespongiformencephalopathy.blogspot.com/2011/06/experimental-h-type-bovine-spongiform.html
LET'S take a closer look at this new prionpathy or prionopathy, and then let's look at the g-h-BSEalabama mad cow.
This new prionopathy in humans? the genetic makeup is IDENTICAL to the g-h-BSEalabama mad cow, the only _documented_ mad cow in the world to date like this, ......wait, it get's better. this new prionpathy is killing young and old humans, with LONG DURATION from onset of symptoms to death, and the symptoms are very similar to nvCJD victims, OH, and the plaques are very similar in some cases too, bbbut, it's not related to the g-h-BSEalabama cow, WAIT NOW, it gets even better, the new human prionpathy that they claim is a genetic TSE, has no relation to any gene mutation in that family. daaa, ya think it could be related to that mad cow with the same genetic make-up ??? there were literally tons and tons of banned mad cow protein in Alabama in commerce, and none of it transmitted to cows, and the cows to humans there from ??? r i g h t $$$
ALABAMA MAD COW g-h-BSEalabama
In this study, we identified a novel mutation in the bovine prion protein gene (Prnp), called E211K, of a confirmed BSE positive cow from Alabama, United States of America. This mutation is identical to the E200K pathogenic mutation found in humans with a genetic form of CJD. This finding represents the first report of a confirmed case of BSE with a potential pathogenic mutation within the bovine Prnp gene. We hypothesize that the bovine Prnp E211K mutation most likely has caused BSE in "the approximately 10-year-old cow" carrying the E221K mutation.
http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1000156
http://www.plospathogens.org/article/fetchObjectAttachment.action?uri=info%3Adoi%2F10.1371%2Fjournal.ppat.1000156&representation=PDF
Saturday, August 14, 2010
BSE Case Associated with Prion Protein Gene Mutation (g-h-BSEalabama) and VPSPr PRIONPATHY
(see mad cow feed in COMMERCE IN ALABAMA...TSS)
http://prionpathy.blogspot.com/2010/08/bse-case-associated-with-prion-protein.html
her healthy calf also carried the mutation (J. A. Richt and S. M. Hall PLoS Pathog. 4, e1000156; 2008).
This raises the possibility that the disease could occasionally be genetic in origin. Indeed, the report of the UK BSE Inquiry in 2000 suggested that the UK epidemic had most likely originated from such a mutation and argued against the scrapierelated assumption. Such rare potential pathogenic PRNP mutations could occur in countries at present considered to be free of BSE, such as Australia and New Zealand. So it is important to maintain strict surveillance for BSE in cattle, with rigorous enforcement of the ruminant feed ban (many countries still feed ruminant proteins to pigs). Removal of specified risk material, such as brain and spinal cord, from cattle at slaughter prevents infected material from entering the human food chain. Routine genetic screening of cattle for PRNP mutations, which is now available, could provide additional data on the risk to the public. Because the point mutation identified in the Alabama animals is identical to that responsible for the commonest type of familial (genetic) CJD in humans, it is possible that the resulting infective prion protein might cross the bovine-human species barrier more easily. Patients with vCJD continue to be identified. The fact that this is happening less often should not lead to relaxation of the controls necessary to prevent future outbreaks.
Malcolm A. Ferguson-Smith Cambridge University Department of Veterinary Medicine, Madingley Road, Cambridge CB3 0ES, UK e-mail: maf12@cam.ac.uk Jürgen A. Richt College of Veterinary Medicine, Kansas State University, K224B Mosier Hall, Manhattan, Kansas 66506-5601, USA
NATURE|Vol 457|26 February 2009
http://www.nature.com/nature/journal/v457/n7233/full/4571079b.html
P.9.21
Molecular characterization of BSE in Canada
Jianmin Yang1, Sandor Dudas2, Catherine Graham2, Markus Czub3, Tim McAllister1, Stefanie Czub1 1Agriculture and Agri-Food Canada Research Centre, Canada; 2National and OIE BSE Reference Laboratory, Canada; 3University of Calgary, Canada
Background: Three BSE types (classical and two atypical) have been identified on the basis of molecular characteristics of the misfolded protein associated with the disease. To date, each of these three types have been detected in Canadian cattle.
Objectives: This study was conducted to further characterize the 16 Canadian BSE cases based on the biochemical properties of there associated PrPres. Methods: Immuno-reactivity, molecular weight, glycoform profiles and relative proteinase K sensitivity of the PrPres from each of the 16 confirmed Canadian BSE cases was determined using modified Western blot analysis.
Results: Fourteen of the 16 Canadian BSE cases were C type, 1 was H type and 1 was L type. The Canadian H and L-type BSE cases exhibited size shifts and changes in glycosylation similar to other atypical BSE cases. PK digestion under mild and stringent conditions revealed a reduced protease resistance of the atypical cases compared to the C-type cases. N terminal- specific antibodies bound to PrPres from H type but not from C or L type. The C-terminal-specific antibodies resulted in a shift in the glycoform profile and detected a fourth band in the Canadian H-type BSE.
Discussion: The C, L and H type BSE cases in Canada exhibit molecular characteristics similar to those described for classical and atypical BSE cases from Europe and Japan. This supports the theory that the importation of BSE contaminated feedstuff is the source of C-type BSE in Canada. *** It also suggests a similar cause or source for atypical BSE in these countries.
http://www.prion2009.com/sites/default/files/Prion2009_Book_of_Abstracts.pdf
Saturday, July 23, 2011
CATTLE HEADS WITH TONSILS, BEEF TONGUES, SPINAL CORD, SPECIFIED RISK MATERIALS (SRM's) AND PRIONS, AKA MAD COW DISEASE
http://transmissiblespongiformencephalopathy.blogspot.com/2011/07/cattle-heads-with-tonsils-beef-tongues.html
Saturday, November 6, 2010
TAFS1 Position Paper on Position Paper on Relaxation of the Feed Ban in the EU Berne, 2010 TAFS
INTERNATIONAL FORUM FOR TRANSMISSIBLE ANIMAL DISEASES AND FOOD SAFETY a non-profit Swiss Foundation
http://madcowfeed.blogspot.com/2010/11/tafs1-position-paper-on-position-paper.html
Archive Number 20101206.4364 Published Date 06-DEC-2010 Subject PRO/AH/EDR> Prion disease update 2010 (11)
PRION DISEASE UPDATE 2010 (11)
http://www.promedmail.org/direct.php?id=20101206.4364
October 2009
O.11.3
Infectivity in skeletal muscle of BASE-infected cattle
Silvia Suardi1, Chiara Vimercati1, Fabio Moda1, Ruggerone Margherita1, Ilaria Campagnani1, Guerino Lombardi2, Daniela Gelmetti2, Martin H. Groschup3, Anne Buschmann3, Cristina Casalone4, Maria Caramelli4, Salvatore Monaco5, Gianluigi Zanusso5, Fabrizio Tagliavini1 1Carlo Besta" Neurological Institute,Italy; 2IZS Brescia, Italy; 33FLI Insel Riems, D, Germany; 4CEA-IZS Torino, Italy; 5University of Verona, Italy
Background: BASE is an atypical form of bovine spongiform encephalopathy caused by a prion strain distinct from that of BSE. Upon experimental transmission to cattle, BASE induces a previously unrecognized disease phenotype marked by mental dullness and progressive atrophy of hind limb musculature. Whether affected muscles contain infectivity is unknown. This is a critical issue since the BASE strain is readily transmissible to a variety of hosts including primates, suggesting that humans may be susceptible.
Objectives: To investigate the distribution of infectivity in peripheral tissues of cattle experimentally infected with BASE. Methods: Groups of Tg mice expressing bovine PrP (Tgbov XV, n= 7-15/group) were inoculated both i.c. and i.p. with 10% homogenates of a variety of tissues including brain, spleen, cervical lymph node, kidney and skeletal muscle (m. longissimus dorsi) from cattle intracerebrally infected with BASE. No PrPres was detectable in the peripheral tissues used for inoculation either by immunohistochemistry or Western blot.
Results: Mice inoculated with BASE-brain homogenates showed clinical signs of disease with incubation and survival times of 175±15 and 207±12 days. Five out of seven mice challenged with skeletal muscle developed a similar neurological disorder, with incubation and survival times of 380±11 and 410±12 days. At present (700 days after inoculation) mice challenged with the other peripheral tissues are still healthy. The neuropathological phenotype and PrPres type of the affected mice inoculated either with brain or muscle were indistinguishable and matched those of Tgbov XV mice infected with natural BASE.
Discussion: Our data indicate that the skeletal muscle of cattle experimentally infected with BASE contains significant amount of infectivity, at variance with BSE-affected cattle, raising the issue of intraspecies transmission and the potential risk for humans. Experiments are in progress to assess the presence of infectivity in skeletal muscles of natural BASE.
http://www.prion2009.com/sites/default/files/Prion2009_Book_of_Abstracts.pdf
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.
http://ww2.isid.org/Downloads/14th_ICID_ISE_Abstracts.pdf
STRICTLY PRIVATE AND CONFIDENTIAL 25, AUGUST 1995
snip...
To minimise the risk of farmers' claims for compensation from feed compounders.
To minimise the potential damage to compound feed markets through adverse publicity.
To maximise freedom of action for feed compounders, notably by maintaining the availability of meat and bone meal as a raw material in animal feeds, and ensuring time is available to make any changes which may be required.
snip...
THE FUTURE
4..........
MAFF remains under pressure in Brussels and is not skilled at handling potentially explosive issues.
5. Tests _may_ show that ruminant feeds have been sold which contain illegal traces of ruminant protein. More likely, a few positive test results will turn up but proof that a particular feed mill knowingly supplied it to a particular farm will be difficult if not impossible.
6. The threat remains real and it will be some years before feed compounders are free of it. The longer we can avoid any direct linkage between feed milling _practices_ and actual BSE cases, the more likely it is that serious damage can be avoided. ...
SEE full text ;
http://web.archive.org/web/20060517074958/http://www.bseinquiry.gov.uk/files/yb/1995/08/24002001.pdf
2011
Monday, September 26, 2011
L-BSE BASE prion and atypical sporadic CJD
http://bse-atypical.blogspot.com/2011/09/l-bse-base-prion-and-atypical-sporadic.html
Monday, May 23, 2011
Atypical Prion Diseases in Humans and Animals 2011 Top Curr Chem (2011)
DOI: 10.1007/128_2011_161
# Springer-Verlag Berlin Heidelberg 2011
Atypical Prion Diseases in Humans and Animals
Michael A. Tranulis, Sylvie L. Benestad, Thierry Baron, and Hans Kretzschmar
Abstract
Although prion diseases, such as Creutzfeldt–Jakob disease (CJD) in humans and scrapie in sheep, have long been recognized, our understanding of their epidemiology and pathogenesis is still in its early stages. Progress is hampered by the lengthy incubation periods and the lack of effective ways of monitoring and characterizing these agents. Protease-resistant conformers of the prion protein (PrP), known as the “scrapie form” (PrPSc), are used as disease markers, and for taxonomic purposes, in correlation with clinical, pathological, and genetic data. In humans, prion diseases can arise sporadically (sCJD) or genetically (gCJD and others), caused by mutations in the PrP-gene (PRNP), or as a foodborne infection, with the agent of bovine spongiform encephalopathy (BSE) causing variant CJD (vCJD). Person-to-person spread of human prion disease has only been known to occur following cannibalism (kuru disease in Papua New Guinea) or through medical or surgical treatment (iatrogenic CJD, iCJD). In contrast, scrapie in small ruminants and chronic wasting disease (CWD) in cervids behave as infectious diseases within these species. Recently, however, so-called atypical forms of prion diseases have been discovered in sheep (atypical/Nor98 scrapie) and in cattle, BSE-H and BSE-L. These maladies resemble sporadic or genetic human prion diseases and might be their animal equivalents. This hypothesis also raises the significant public health question of possible epidemiological links between these diseases and their counterparts in humans.
M.A. Tranulis (*)
Norwegian School of Veterinary Science, Oslo, Norway
e-mail: Michael.Tranulis@nvh.no
S.L. Benestad
Norwegian Veterinary Institute, Oslo, Norway
T. Baron
Agence Nationale de Se´curite´ Sanitaire, ANSES, Lyon, France
H. Kretzschmar
Ludwig–Maximilians University of Munich, Munich, Germany
Keywords Animal Atypical Atypical/Nor98 scrapie BSE-H BSE-L Human Prion disease Prion strain Prion type
http://resources.metapress.com/pdf-preview.axd?code=f433r34h34ugg617&size=largest
see full text and more here ;
http://bse-atypical.blogspot.com/2011/05/atypical-prion-diseases-in-humans-and.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
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
Monday, April 25, 2011
Experimental Oral Transmission of Atypical Scrapie to Sheep
Volume 17, Number 5-May 2011
http://nor-98.blogspot.com/2011/04/experimental-oral-transmission-of.html
Thursday, June 2, 2011
USDA scrapie report for April 2011 NEW ATYPICAL NOR-98 SCRAPIE CASES Pennsylvania AND California
http://nor-98.blogspot.com/2011/06/usda-scrapie-report-for-april-2011-new.html
Monday, June 20, 2011 2011
Annual Conference of the National Institute for Animal Agriculture ATYPICAL NOR-98 LIKE SCRAPIE UPDATE USA
http://nor-98.blogspot.com/2011/06/2011-annual-conference-of-national.html
Thursday, July 14, 2011
Histopathological Studies of "CH1641-Like" Scrapie Sources Versus Classical Scrapie and BSE Transmitted to Ovine Transgenic Mice (TgOvPrP4)
http://transmissiblespongiformencephalopathy.blogspot.com/2011/07/histopathological-studies-of-ch1641.html
Wednesday, October 12, 2011
White-tailed deer are susceptible to the agent of sheep scrapie by intracerebral inoculation
http://chronic-wasting-disease.blogspot.com/2011/10/white-tailed-deer-are-susceptible-to.html
Monday, November 14, 2011
WYOMING Creutzfeldt Jakob Disease, CWD, TSE, PRION REPORTING 2011
http://transmissiblespongiformencephalopathy.blogspot.com/2011/11/wyoming-creutzfeldt-jakob-disease-cwd.html
UPDATED DATA ON 2ND CWD STRAIN
Wednesday, September 08, 2010
CWD PRION CONGRESS SEPTEMBER 8-11 2010
http://chronic-wasting-disease.blogspot.com/2010/09/cwd-prion-2010.html
Wednesday, January 5, 2011
ENLARGING SPECTRUM OF PRION-LIKE DISEASES Prusiner Colby et al 2011
Prions
David W. Colby1,* and Stanley B. Prusiner1,2
http://betaamyloidcjd.blogspot.com/2011/01/enlarging-spectrum-of-prion-like.html
Wednesday, November 09, 2011
Case report Sporadic fatal insomnia in a young woman: A diagnostic challenge: Case Report TEXAS
HOW TO TURN A POTENTIAL MAD COW VICTIM IN THE USA, INTO A HAPPENSTANCE OF BAD LUCK, A SPONTANEOUS MUTATION FROM NOTHING.
OR WAS IT $$$
http://creutzfeldt-jakob-disease.blogspot.com/2011/11/case-report-sporadic-fatal-insomnia-in.html
Tuesday, November 08, 2011
Can Mortality Data Provide Reliable Indicators for Creutzfeldt-Jakob Disease Surveillance? A Study in France from 2000 to 2008 Vol. 37, No. 3-4, 2011
Original Paper
Conclusions:These findings raise doubt about the possibility of a reliable CJD surveillance only based on mortality data.
http://creutzfeldt-jakob-disease.blogspot.com/2011/11/can-mortality-data-provide-reliable.html
U.S.A. HIDING MAD COW DISEASE VICTIMS AS SPORADIC CJD ? (see video at bottom)
http://creutzfeldt-jakob-disease.blogspot.com/2009/07/usa-hiding-mad-cow-disease-victims-as.html
2006
USA sporadic CJD cases rising ;
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
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
CJD USA RISING, with UNKNOWN PHENOTYPE ;
5 Includes 41 cases in which the diagnosis is pending, and 17 inconclusive cases;
*** 6 Includes 46 cases with type determination pending in which the diagnosis of vCJD has been excluded.
http://www.cjdsurveillance.com/pdf/case-table.pdf
Thursday, August 4, 2011
Terry Singeltary Sr. on the Creutzfeldt-Jakob Disease Public Health Crisis, Date aired: 27 Jun 2011 (SEE VIDEO)
http://transmissiblespongiformencephalopathy.blogspot.com/2011/08/terry-singeltary-sr-on-creutzfeldt.html
Sunday, August 21, 2011
The British disease, or a disease gone global, The TSE Prion Disease (SEE VIDEO)
http://transmissiblespongiformencephalopathy.blogspot.com/2011/08/british-disease-or-disease-gone-global.html
Saturday, March 5, 2011
MAD COW ATYPICAL CJD PRION TSE CASES WITH CLASSIFICATIONS PENDING ON THE RISE IN NORTH AMERICA
http://transmissiblespongiformencephalopathy.blogspot.com/2011/03/mad-cow-atypical-cjd-prion-tse-cases.html
Friday, November 04, 2011
Diagnostic accuracy of cerebrospinal fluid protein markers for sporadic Creutzfeldt-Jakob disease in Canada: a 6-year prospective study Research article
http://creutzfeldt-jakob-disease.blogspot.com/2011/11/diagnostic-accuracy-of-cerebrospinal.html
WHO WILL FOLLOW THE CHILDREN FOR CJD SYMPTOMS ???
Saturday, May 2, 2009
U.S. GOVERNMENT SUES WESTLAND/HALLMARK MEAT OVER USDA CERTIFIED DEADSTOCK DOWNER COW SCHOOL LUNCH PROGRAM
http://downercattle.blogspot.com/2009/05/us-government-sues-westlandhallmark.html
http://downercattle.blogspot.com/
Friday, November 18, 2011
country-of-origin labeling law (COOL) violates U.S. obligations under WTO rules WT/DS384/R WT/DS386/R
http://naiscoolyes.blogspot.com/2011/11/country-of-origin-labeling-law-cool.html
Thursday, November 17, 2011
International cattle ID and traceability: Competitive implications for the US
Food Policy Volume 37, Issue 1, February 2012, Pages 31-40
http://naiscoolyes.blogspot.com/2011/11/international-cattle-id-and.html
Tuesday, November 15, 2011
Alternative BSE Risk Assessment Methodology of Imported Beef and Beef Offal to Japan Journal of Veterinary Medical Science
Advance Publication
http://transmissiblespongiformencephalopathy.blogspot.com/2011/11/alternative-bse-risk-assessment.html
TSS
Novel Prion Protein in BSE-affected Cattle, Switzerland
To the Editor:
Bovine spongiform encephalopathy (BSE) is a feed-borne prion disease that affects mainly cattle but also other ruminants, felids, and humans (1). Currently, 3 types of BSE have been distinguished by Western immunoblot on the basis of the signature of the proteinase K–resistant fragment of the pathologic prion protein (PrPres): the classic type of BSE (C-BSE) and 2 so-called atypical types of BSE with higher or lower molecular masses of PrPres (H-BSE and L-BSE, respectively) (2). C-BSE is transmitted to cattle by ingestion of contaminated meat-and-bone meal, a feed supplement produced from animal carcasses and by-products. H-BSE and L-BSE have been identified by active disease surveillance, and incidence in aged cattle is low; but little is known about their epidemiology, pathobiology, and zoonotic potential (3). We describe 2 recent cases of BSE in aged cattle in Switzerland in which a PrPres phenotype distinct from those of C-, L- and H-BSE was unexpectedly displayed.
In April 2011, an 8-year-old cow (cow 1) died of accidental injury, with no apparent precedent clinical signs, on a farm in the canton of St. Gallen, Switzerland. In the context of active surveillance for BSE, the medulla oblongata was tested and found to be BSE positive by using the PrioStrip test (Prionics AG, Schlieren, Switzerland), a lateral-flow immunochromatographic assay for detection of PrPres. One month later, another cow (cow 2), 15 years of age, in the canton of Berne, Switzerland, was slaughtered because of a hind limb fracture. Information on this animal’s health status before death was unavailable. Statutory testing of the medulla oblongata gave a BSE-positive result by using the Prionics Check Western, a rapid Western blot technique (4). Medulla oblongata samples from the 2 animals were forwarded to the National Reference Laboratory for confirmatory testing.
In accordance with the guidelines of the World Organisation for Animal Health (5), BSE was confirmed for each animal by positive test results in independent, approved screening tests, of which 1 must be a Western blot (online Technical Appendix, wwwnc.cdc.gov/EID/pdfs/11-1225-Techapp.pdf). Because the tissues were severely autolyzed, target structures for the diagnosis of BSE could not be identified, and histopathologic and immunohistochemical results were inconclusive.
The Prionics Western blot detected a similar 3-band PrPres glycoprofile with molecular masses of roughly 16, 20, and 25 kDa for each animal, lower than equivalent PrP protein bands detected in animals with C-BSE (Figure). Sequencing of the open reading frame of the PRNP gene of cow 2 (which was unsuccessful for cow 1) indicated that the encoded protein was identical to the common bovine PrP amino acid sequence (as translated from GenBank accession no. AJ298878) and therefore was not likely to account for the differences observed by Western blot testing.
We next investigated which region of the prion protein was present in these abberant PrPres fragments by probing with a panel of antibodies in the Western blot that bind to different regions of the prion protein (online Technical Appendix). PrPres in cows 1 and 2 was readily detected by antibodies Sha31, 94B4, and JB10. By contrast, antibody 9A2, which maps to the PrPres N terminus, bound only to PrPres in samples from animals with C-, L- and H- BSE but not in samples from cows 1 and 2. The molecular masses of the PrPres moieties from the 2 cows were also clearly distinct from those from controls with L- and H-BSE (Figure). For samples from animals with H-BSE, enzymatic deglycosylation demonstrated PrPres subtypes, 1 and 2, the latter being a C-terminal PrPres fragment of 12–14 kDa (6). To investigate whether the novel PrPres type corresponds to PrPres subtype 2, we compared samples from cow 2 with those from the H-BSE control by Western blot. The PrPres type from the 2 cows reported here and PrPres subtype 2 from the H-BSE control were indeed distinct (Figure).
We report a novel PrPres signature in 2 cows with BSE diagnoses determined according to established criteria. Combining Western blot analysis with an epitope mapping strategy, we ascertained that these animals displayed an N terminally truncated PrPres different from currently classified BSE prions (Figure). The interpretation of these findings remains difficult because neuropathologic and systematic clinical data for the 2 cases are not available. Moreover, the tissue samples were autolyzed, and the question of whether this affected the PrPres molecular signature is of concern. Nonetheless, our findings raise the possibility that these cattle were affected by a prion disease not previously encountered and distinct from the known types of BSE. To confirm this possibility and to assess a potential effect on disease control and public health, in vivo transmission studies using transgenic mouse models and cattle are ongoing. Until results of these studies are available, molecular diagnostic techniques should be used so that such cases are not missed.
Acknowledgments
We thank the BSE screening laboratories at the Center of Laboratory Medicine (ZLM, St. Gallen, Switzerland), Prionics AG, and the veterinary services of the cantons of St. Gallen and Berne for their support. We also thank Jan P.M. Langeveld for kindly providing antibodies 9A2 and 94B4.
This work was financed with resources provided by the Swiss Federal Veterinary Office.
Torsten Seuberlich, Michaela Gsponer, Cord Drögemüller, Miroslaw P. Polak, Sandra McCutcheon, Dagmar Heim, Anna Oevermann, and Andreas Zurbriggen
Author affiliations: University of Berne, Berne, Switzerland (T. Seuberlich, M. Gsponer, C. Drögemüller, A. Oevermann, A. Zurbriggen); National Veterinary Research Institute, Pulawy, Poland (M.P. Polak); University of Edinburgh, Edinburgh, Scotland, UK (S. McCutcheon); and Federal Veterinary Office, Liebefeld, Switzerland (Dagmar Heim)
References
snip...full text ;
http://wwwnc.cdc.gov/eid/pdfs/11-1225-ahead_of_print.pdf?source=govdelivery
=========UPDATE DECEMBER 16, 2011========
TSENEWS
New atypical BSE in two Swiss cows?
In spring 2011, two new cases of BSE were discovered in Switzerland. Both cases were detected using the Prionics®-Check BSE tests. A report has now been published showing that these cases represent a novel type of BSE. What are the consequences of these new BSE cases?
After a period of four years without BSE positive cows, in spring this year Switzerland was shaken by the discovery of two new BSE cases detected only one month apart from each other. The cases appeared in different areas of Switzerland and involved animals aged 8 and 15 years, which were tested with the Prionics®-Check BSE tests as part of the active disease surveillance program. Bettina Bernhard, Head of the Prionics diagnostic laboratory reported that: “It was the first time in 4½ years that we had found a BSE positive sample in our laboratory. Based on the results from the Prionics®-Check WESTERN, we immediately saw that the fingerprint of the prion protein was not that of the classical BSE cases we have detected before. We then informed the Swiss National Reference Laboratory and veterinary authorities and the positive result was confirmed with the Prionics®-Check PrioSTRIP.”
Novel type of BSE? BSE cases that differ from the classical BSE strain have been detected before, however, with low incidence. These atypical strains, designated BASE/L-BSE and H-BSE, were first reported in 2004 in Italy and France. Both strains were detected as part of routine surveillance using the Prionics®-Check WESTERN and ELISA tests. The recent publication by Torsten Seuberlich of the Swiss National and OIE1 Reference Laboratories for BSE and Scrapie and his colleagues, is showing that these two Swiss cases not only differ from classical BSE, but also from the atypical BSE cases found in other countries (see figure "Fingerprint of prion proteins"). It appears that the two BSE cases detected in Switzerland seem to represent a novel type of atypical BSE. Dr. Seuberlich explains: “We are now undertaking further investigations into these two cases and until there is more clarity, surveillance should continue to be carried out at a high level and disease awareness should be increased. Furthermore, we have to ensure that diagnostic techniques are applied that identify such cases.”
Continued vigilance needed Whereas consumption of meat from cows affected by classical BSE has been associated with vCJD, the public health hazard from atypical BSE is unclear. Little is known about its origin and whether it can be transmitted to other animals. These cases show, however, that BSE has not been completely eradicated and that the disease can continue to occur even with current preventive measures (e.g. the meat-and-bone meal ban) in place. The appearance of new strains of the prion protein could also indicate that BSE is still evolving. Continuous monitoring will be needed to keep these new strains under surveillance.
1World Organisation for Animal Health
tss
=======END UPDATE DECEMBER 16, 2011=============
P.4.23
Transmission of atypical BSE in humanized mouse models
Liuting Qing1, Wenquan Zou1, Cristina Casalone2, Martin Groschup3, Miroslaw Polak4, Maria Caramelli2, Pierluigi Gambetti1, Juergen Richt5, Qingzhong Kong1 1Case Western Reserve University, USA; 2Instituto Zooprofilattico Sperimentale, Italy; 3Friedrich-Loeffler-Institut, Germany; 4National Veterinary Research Institute, Poland; 5Kansas State University (Previously at USDA National Animal Disease Center), USA
Background: 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). Atypical BSE cases have been discovered in three continents since 2004; they include the L-type (also named BASE), the H-type, and the first reported case of naturally occurring BSE with mutated bovine PRNP (termed BSE-M). The public health risks posed by atypical BSE were largely undefined.
Objectives: To investigate these atypical BSE types in terms of their transmissibility and phenotypes in humanized mice. Methods: Transgenic mice expressing human PrP were inoculated with several classical (C-type) and atypical (L-, H-, or Mtype) BSE isolates, and the transmission rate, incubation time, characteristics and distribution of PrPSc, symptoms, and histopathology were or will be examined and compared.
Results: Sixty percent of BASE-inoculated humanized mice became infected with minimal spongiosis and an average incubation time of 20-22 months, whereas only one of the C-type BSE-inoculated mice developed prion disease after more than 2 years. Protease-resistant PrPSc in BASE-infected humanized Tg mouse brains was biochemically different from bovine BASE or sCJD. PrPSc was also detected in the spleen of 22% of BASE-infected humanized mice, but not in those infected with sCJD. Secondary transmission of BASE in the humanized mice led to a small reduction in incubation time.*** The atypical BSE-H strain is also transmissible with distinct phenotypes in the humanized mice, but no BSE-M transmission has been observed so far.
Discussion: Our results demonstrate that BASE is more virulent than classical BSE, has a lymphotropic phenotype, and displays a modest transmission barrier in our humanized mice. BSE-H is also transmissible in our humanized Tg mice. The possibility of more than two atypical BSE strains will be discussed.
Supported by NINDS NS052319, NIA AG14359, and NIH AI 77774.
http://www.prion2009.com/sites/default/files/Prion2009_Book_of_Abstracts.pdf
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
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 ;
.....snip
''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.''
Best regards, Qingzhong Kong, PhD Associate Professor Department of Pathology Case Western Reserve University Cleveland, OH 44106 USA
END...TSS
Thursday, December 04, 2008 2:37 PM
"we have found that H-BSE can infect humans."
personal communication with Professor Kong. ...TSS
BSE-H is also transmissible in our humanized Tg mice.
The possibility of more than two atypical BSE strains will be discussed.
Supported by NINDS NS052319, NIA AG14359, and NIH AI 77774.
http://www.prion2009.com/sites/default/files/Prion2009_Book_of_Abstracts.pdf
http://transmissiblespongiformencephalopathy.blogspot.com/2011/06/experimental-h-type-bovine-spongiform.html
=====================
"The origin of atypical BSE is not yet determined. According to EFSA's scientific opinion published in 2008, all the cases of atypical BSE were reported with birth dates before the real feed ban in January 2001 in Europe. Therefore, the possibility of those atypical cases attributing to the contaminated feeds, just as in classical BSE, cannot be completely denied."
=====================
atypical BSE TSE cases have been around for a long long time, so yes indeed MBM or SRM could very well and most likely did contain atypical TSE of all strains in the USA, and the typical strains as well, of all species. the North America and the USA has typical and atypical BSE, typical and atypical Scrapie, and two strains now of Chronic Wasting Disease, call them typical and atypical, or call them what you want, all this has been rendered and fed to food producing livestock for humans and animals for years in the USA. these are the facts, like them or not. please see ;
1992
IN CONFIDENCE
BSE - ATYPICAL LESION DISTRIBUTION (RBSE 92-21367)
http://tna.europarchive.org/20080609145105/http://www.bseinquiry.gov.uk/files/yb/1993/03/14001001.pdf
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 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://collections.europarchive.org/tna/20090114131343/http://www.bseinquiry.gov.uk/files/yb/1992/10/26001001.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
''THE LINE TO TAKE'' ON IBNC $$$ 1995 $$$
1995
page 9 of 14 ;
30. The Committee noted that the results were unusual. the questioned whether there could be coincidental BSE infection or contamination with scrapie. Dr. Tyrell noted that the feeling of the committee was that this did not represent a new agent but it was important to be prepared to say something publicly about these findings. A suggested line to take was that these were scientifically unpublishable results but in line with the policy of openness they would be made publicly available and further work done to test their validity. Since the BSE precautions were applied to IBNC cases, human health was protected. Further investigations should be carried out on isolations from brains of IBNC cases with removal of the brain and subsequent handling under strict conditions to avoid the risk of any contamination.
31. Mr. Bradley informed the Committee that the CVO had informed the CMO about the IBNC results and the transmission from retina and he, like the Committee was satisfied that the controls already in place or proposed were adequate. ...
snip... see full text
http://collections.europarchive.org/tna/20080102204938/http://www.bseinquiry.gov.uk/files/yb/1995/06/21005001.pdf
http://web.archive.org/web/20030327015011/http://www.bseinquiry.gov.uk/files/yb/1995/06/21005001.pdf
NOW, what about the 'obex only' mode of testing used by the USDA et al for TSE, prions $$$ works for them too, a sure fire way NOT TO FIND MAD COW DISEASE $$$
NOW, read the following please, and then ask yourself, WHY the USDA et al were ONLY TESTING THE OBEX PART OF THE BRAIN in USA cattle for BSE $$$
BECAUSE they knew that would be the least likely way to find BSE/TSE in USA cattle $$$...TSS
Tuesday, November 02, 2010
IN CONFIDENCE
The information contained herein should not be disseminated further except on the basis of "NEED TO KNOW".
BSE - ATYPICAL LESION DISTRIBUTION (RBSE 92-21367) statutory (obex only) diagnostic criteria CVL 1992
http://bse-atypical.blogspot.com/2010/11/bse-atypical-lesion-distribution-rbse.html
1979
In May, 1990 (J/AVMA/196/1679) a paper was published in the Journal of the American Veterinary Medical Association detailing work on the transmission of scrapie to cattle initiated by the USDA at Mission, Texas, in January, 1979. In this study, ten calves were each challenged intracerebrally, orally, intramuscularly and subcutaneously with scrapie which had been subpassaged in either a sheep or a goat.Three of these animals went on to develop clinical symptoms of a spongiform encephalopathy which differed from those seen with BSE infection. PrP was detected in tissues from these cattle, but neurohistologically the changes seen in the brains from these cattle were consistent with scrapie and differed from BSE. Material from the affected cattle was bioassayed in mice which were observed for 2 years. The mice remained clinically and neurohistologically negative *** apart from one group which,although they showed CNS signs, were histologically negative.
http://www.bseinquiry.gov.uk/files/ws/s100bxii.pdf
http://74.125.47.132/search?q=cache:Geyf-zmNTSkJ:www.bseinquiry.gov.uk/files/ws/s100bxii.pdf+mission+texas+bse+inquiry+yb&cd=1&hl=en&ct=clnk&gl=us
3.56 A further difference in the transmission properties of the two diseases was the pattern of disease caused in the brains of experimental animals. Mice inoculated with scrapie material from geographically and temporally distinct sources were found to have variable brain lesions, whereas mice inoculated with BSE material similarly derived from different sources all had very similar patterns of disease. 30 These results showed that, unlike scrapie, only one strain of BSE was present in the inocula derived from different sources. As the current hypothesis suggested that scrapie had transmitted to cattle at a number of geographically separate sites, it might have been expected that several strains of BSE would have been evident, given that over 20 strains of scrapie were known. Since 1996, strain-typing studies in mice have shown that the lesion profile produced by BSE is different to all known scrapie strains. 31
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. 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.
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, 35 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. 36 It was also felt that the results of such an experiment would be hard to interpret. While a negative result 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. 37 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. 38
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.
http://web.archive.org/web/20010224062436/http://www.bseinquiry.gov.uk/report/volume2/chaptea3.htm#820550
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
http://www.bseinquiry.gov.uk/files/yb/1988/10/00001001.pdf
http://www.bseinquiry.gov.uk/report/volume2/chaptea3.htm#820546
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.
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, 35 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. 36 It was also felt that the results of such an experiment would be hard to interpret. While a negative result 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. 37 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. 38
http://www.bseinquiry.gov.uk/report/volume2/chaptea3.htm#820550
http://www.bseinquiry.gov.uk/report/volume2/chaptea3.htm
Saturday, June 25, 2011
Transmissibility of BSE-L and Cattle-Adapted TME Prion Strain to Cynomolgus Macaque
"BSE-L in North America may have existed for decades"
http://transmissiblespongiformencephalopathy.blogspot.com/2011/06/transmissibility-of-bse-l-and-cattle.html
EFSA Journal 2011 The European Response to BSE: A Success Story
This is an interesting editorial about the Mad Cow Disease debacle, and it's ramifications that will continue to play out for decades to come ;
Monday, October 10, 2011
EFSA Journal 2011 The European Response to BSE: A Success Story
snip...
EFSA and the European Centre for Disease Prevention and Control (ECDC) recently delivered a scientific opinion on any possible epidemiological or molecular association between TSEs in animals and humans (EFSA Panel on Biological Hazards (BIOHAZ) and ECDC, 2011). This opinion confirmed Classical BSE prions as the only TSE agents demonstrated to be zoonotic so far but the possibility that a small proportion of human cases so far classified as "sporadic" CJD are of zoonotic origin could not be excluded. Moreover, transmission experiments to non-human primates suggest that some TSE agents in addition to Classical BSE prions in cattle (namely L-type Atypical BSE, Classical BSE in sheep, transmissible mink encephalopathy (TME) and chronic wasting disease (CWD) agents) might have zoonotic potential.
snip...
http://www.efsa.europa.eu/en/efsajournal/pub/e991.htm?emt=1
http://www.efsa.europa.eu/en/efsajournal/doc/e991.pdf
see follow-up here about North America BSE Mad Cow TSE prion risk factors, and the ever emerging strains of Transmissible Spongiform Encephalopathy in many species here in the USA, including humans ;
http://transmissiblespongiformencephalopathy.blogspot.com/2011/10/efsa-journal-2011-european-response-to.html
Wednesday, March 31, 2010
Atypical BSE in Cattle
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.
http://www.prionetcanada.ca/detail.aspx?menu=5&dt=293380&app=93&cat1=387&tp=20&lk=no&cat2
Thursday, August 12, 2010
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
Rural and Regional Affairs and Transport References Committee
The possible impacts and consequences for public health, trade and agriculture of the Government's decision to relax import restrictions on beef Final report June 2010
2.66 Dr Fahey also told the committee that in the last two years a link has been established between forms of atypical CJD and atypical BSE. Dr Fahey said that: They now believe that those atypical BSEs overseas are in fact causing sporadic Creutzfeldt-Jakob disease. They were not sure if it was due to mad sheep disease or a different form. If you look in the textbooks it looks like this is just arising by itself. But in my research I have a summary of a document which states that there has never been any proof that sporadic Creutzfeldt-Jakob disease has arisen de novo-has arisen of itself. There is no proof of that. The recent research is that in fact it is due to atypical forms of mad cow disease which have been found across Europe, have been found in America and have been found in Asia. These atypical forms of mad cow disease typically have even longer incubation periods than the classical mad cow disease.50
http://www.aph.gov.au/senate/committee/rrat_ctte/mad_cows/report/report.pdf
And last but not least, similarities of PrPres between Htype BSE and human prion diseases like CJD or GSS have been put forward [10], as well as between L-type BSE and CJD [17]. These findings raise questions about the origin and inter species transmission of these prion diseases that were discovered through the BSE active surveillance.
full text 18 pages ;
http://www.vetres.org/index.php?option=article&access=standard&Itemid=129&url=/articles/vetres/pdf/2008/04/v07232.pdf
please see full text ;
http://bse-atypical.blogspot.com/2008/06/review-on-epidemiology-and-dynamics-of.html
[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.
http://whqlibdoc.who.int/publications/2003/9241545887.pdf
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/direct.php?id=20100405.1091
CJD RISING SWITZERLAND
CJD is a predominantly sporadic disorder but can also occur as a dominantly inherited or infective condition. Only one of the 26 most recent confirmed cases was identified as carrying a disease related mutation of the PRNP gene, none had identifiable iatrogenic exposure, and none resembled variant CJD. Thus 25 of the 26 cases appear to be sporadic cases. Sporadic CJD is distributed worldwide with a reported incidence of about one in a million per year. Raised awareness of the disease in recent years could account for an increase in reported cases of CJD, although neither an increase in the average age of patients nor more frequent recognition of CJD amongst residents of nursing homes (where dementing illness is prevalent and misdiagnosis might be expected) were seen in the Swiss cases. Moreover, improved ascertainment as an explanation for the observed increase would imply levels of under-reporting in countries other than Switzerland, which appear implausible. The authors of the Lancet report suggest that the rise in cases might be due to some form of unidentified iatrogenic transmission or to exposure to a zoonotic source of infection, though cases do not resemble variant Creutzfeldt-Jakob disease (vCJD). The ongoing surveillance of CJD in Switzerland and the rest of Europe is essential to monitor the situation to see if this rise is sustained in Switzerland, and if a similar rise occurs in other countries (see http://www.eurocjd.ed.ac.uk).
http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=1921
Prion data suggest BSE link to sporadic CJD Declan Butler
Predicting the number of cases of Creutzfeldt-Jakob disease (CJD) in people as a result of transmission of bovine spongiform encephalopathy (BSE) has just got more difficult.Whereas it was thought that BSE only caused a new form of the disease called variant CJD (vCJD), a study in mice from a team led by John Collinge at University College London suggests that it may also cause a disease indistinguishable from the commonest form of classical, or 'sporadic', CJD (E.
http://www.nature.com/nature/journal/v420/n6915/full/420450a.html
Switzerland sporadic CJD ;
Swiss rise in CJD raises concerns over possible BSE link [LONDON] THE LANCET
Plaque attack: Swiss patients have spongiform patterns in the brain typical of sporadic CJD. The number of people dying from Creutzfeldt-Jakob disease (CJD) has risen sharply in Switzerland -- sparking fears of a possible link with bovine spongiform encephalopathy (BSE).
BSE is thought to be the cause of a distinctive form of the brain-wasting disease known as variant CJD. The Swiss cases, in contrast, are standard 'sporadic' CJD. Each year between 1997 and 2000, no more than 11 Swiss people developed CJD. But 19 cases were reported in 2001, and seven were recorded in the first quarter of this year. This is some four times higher than the incidence elsewhere, reports a team led by Adriano Aguzzi of the University Hospital Zurich (M. Glatzel et al. Lancet 360, 139-141; 2002).
The increase could be a mere statistical blip, or it may be due to increased awareness of the disease leading to more diagnoses. More disturbing is the possibility that the cases are linked to the consumption of BSE-infected meat products -- which would mean that the BSE agent can cause two distinct forms of CJD.
Possible links between the Swiss CJD cases and BSE will now be explored by strain-typing experiments in which the disease is transmitted to mice. These tests will take at least a year to complete. "It's the best way to establish or exclude any suspected link," says Moira Bruce of the UK Institute for Animal Health's Neuropathogenesis Unit in Edinburgh.
======================================
Experiences in England and Switzerland -- two countries that discovered mad cow disease in their cattle -- have heightened concerns about the possibility some cases of sporadic CJD are due to consuming mad-cow-tainted beef. Both countries have reported increases in sporadic CJD since mad cow was first detected in British herds in 1986.
Switzerland discovered last year its CJD rate was twice that of any other country in the world. Switzerland had been seeing about eight to 11 cases per year from 1997 to 2000. Then the incidence more than doubled, to 19 cases in 2001 and 18 cases in 2002.
http://www.upi.com/view.cfm?StoryID=20030721-102924-4786r
Mouse model sheds new light on human prion disease
snip...
Professor John Collinge said We are not saying that all or even most cases of sporadic CJD are as a result of BSE exposure, but some more recent cases may be the incidence of sporadic CJD has shown an upward trend in the UK over the last decade. While most of this apparent increase may be because doctors are now more aware of CJD and better at diagnosing it, serious consideration should be given to a proportion of this rise being BSE-related. Switzerland, which has had a substantial BSE epidemic, has noted a sharp recent increase in sporadic CJD.
snip...
http://www.mrc.ac.uk/txt/index/public-interest/public-news-4/public-news_archive/public-news-archive_nov_dec_02/public-bse_and_sporadic_cjd.htm
please see ;
http://creutzfeldt-jakob-disease.blogspot.com/2011/04/sporadic-cjd-rising-text-and-figures-of.html
DR. Adriano Agutzy is one of the world's experts on prion diseases. He says he has ruled out most of the other explanations, and now his main working hypothesis is that at least some Sporadic C.J.D. in Switzerland could be another form of human Mad Cow Disease.
ADRIANO AGUTZY (SCIENTIST):
But this by no means excludes that B.S.E. may manifest itself in humans with different characteristics, and maybe B.S.E. in Switzerland is also different from B.S.E. in the U.K., and then variant C.J.D. will also be different. So I think from the U.K. experience, it's impossible to draw the conclusion that B.S.E. will only give rise to what we know as variant C.J.D.
http://creutzfeldt-jakob-disease.blogspot.com/2009/07/usa-hiding-mad-cow-disease-victims-as.html
please see ;
http://creutzfeldt-jakob-disease.blogspot.com/2011/02/imported-cow-from-switzerland-aged-over.html
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.
http://www.prionetcanada.ca/detail.aspx?menu=5&dt=293380&app=93&cat1=387&tp=20&lk=no&cat2
Tuesday, July 14, 2009
U.S. Emergency Bovine Spongiform Encephalopathy Response Plan Summary and BSE Red Book Date: February 14, 2000 at 8:56 am PST
WHERE did we go wrong $$$
http://madcowtesting.blogspot.com/2009/07/us-emergency-bovine-spongiform.html
SEE FULL TEXT OF ALL THIS HERE ;
2009 UPDATE ON ALABAMA AND TEXAS MAD COWS 2005 and 2006
http://bse-atypical.blogspot.com/2006/08/bse-atypical-texas-and-alabama-update.html
Thursday, June 23, 2011
Experimental H-type bovine spongiform encephalopathy characterized by plaques and glial- and stellate-type prion protein deposits
http://transmissiblespongiformencephalopathy.blogspot.com/2011/06/experimental-h-type-bovine-spongiform.html
LET'S take a closer look at this new prionpathy or prionopathy, and then let's look at the g-h-BSEalabama mad cow.
This new prionopathy in humans? the genetic makeup is IDENTICAL to the g-h-BSEalabama mad cow, the only _documented_ mad cow in the world to date like this, ......wait, it get's better. this new prionpathy is killing young and old humans, with LONG DURATION from onset of symptoms to death, and the symptoms are very similar to nvCJD victims, OH, and the plaques are very similar in some cases too, bbbut, it's not related to the g-h-BSEalabama cow, WAIT NOW, it gets even better, the new human prionpathy that they claim is a genetic TSE, has no relation to any gene mutation in that family. daaa, ya think it could be related to that mad cow with the same genetic make-up ??? there were literally tons and tons of banned mad cow protein in Alabama in commerce, and none of it transmitted to cows, and the cows to humans there from ??? r i g h t $$$
ALABAMA MAD COW g-h-BSEalabama
In this study, we identified a novel mutation in the bovine prion protein gene (Prnp), called E211K, of a confirmed BSE positive cow from Alabama, United States of America. This mutation is identical to the E200K pathogenic mutation found in humans with a genetic form of CJD. This finding represents the first report of a confirmed case of BSE with a potential pathogenic mutation within the bovine Prnp gene. We hypothesize that the bovine Prnp E211K mutation most likely has caused BSE in "the approximately 10-year-old cow" carrying the E221K mutation.
http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1000156
http://www.plospathogens.org/article/fetchObjectAttachment.action?uri=info%3Adoi%2F10.1371%2Fjournal.ppat.1000156&representation=PDF
Saturday, August 14, 2010
BSE Case Associated with Prion Protein Gene Mutation (g-h-BSEalabama) and VPSPr PRIONPATHY
(see mad cow feed in COMMERCE IN ALABAMA...TSS)
http://prionpathy.blogspot.com/2010/08/bse-case-associated-with-prion-protein.html
her healthy calf also carried the mutation (J. A. Richt and S. M. Hall PLoS Pathog. 4, e1000156; 2008).
This raises the possibility that the disease could occasionally be genetic in origin. Indeed, the report of the UK BSE Inquiry in 2000 suggested that the UK epidemic had most likely originated from such a mutation and argued against the scrapierelated assumption. Such rare potential pathogenic PRNP mutations could occur in countries at present considered to be free of BSE, such as Australia and New Zealand. So it is important to maintain strict surveillance for BSE in cattle, with rigorous enforcement of the ruminant feed ban (many countries still feed ruminant proteins to pigs). Removal of specified risk material, such as brain and spinal cord, from cattle at slaughter prevents infected material from entering the human food chain. Routine genetic screening of cattle for PRNP mutations, which is now available, could provide additional data on the risk to the public. Because the point mutation identified in the Alabama animals is identical to that responsible for the commonest type of familial (genetic) CJD in humans, it is possible that the resulting infective prion protein might cross the bovine-human species barrier more easily. Patients with vCJD continue to be identified. The fact that this is happening less often should not lead to relaxation of the controls necessary to prevent future outbreaks.
Malcolm A. Ferguson-Smith Cambridge University Department of Veterinary Medicine, Madingley Road, Cambridge CB3 0ES, UK e-mail: maf12@cam.ac.uk Jürgen A. Richt College of Veterinary Medicine, Kansas State University, K224B Mosier Hall, Manhattan, Kansas 66506-5601, USA
NATURE|Vol 457|26 February 2009
http://www.nature.com/nature/journal/v457/n7233/full/4571079b.html
P.9.21
Molecular characterization of BSE in Canada
Jianmin Yang1, Sandor Dudas2, Catherine Graham2, Markus Czub3, Tim McAllister1, Stefanie Czub1 1Agriculture and Agri-Food Canada Research Centre, Canada; 2National and OIE BSE Reference Laboratory, Canada; 3University of Calgary, Canada
Background: Three BSE types (classical and two atypical) have been identified on the basis of molecular characteristics of the misfolded protein associated with the disease. To date, each of these three types have been detected in Canadian cattle.
Objectives: This study was conducted to further characterize the 16 Canadian BSE cases based on the biochemical properties of there associated PrPres. Methods: Immuno-reactivity, molecular weight, glycoform profiles and relative proteinase K sensitivity of the PrPres from each of the 16 confirmed Canadian BSE cases was determined using modified Western blot analysis.
Results: Fourteen of the 16 Canadian BSE cases were C type, 1 was H type and 1 was L type. The Canadian H and L-type BSE cases exhibited size shifts and changes in glycosylation similar to other atypical BSE cases. PK digestion under mild and stringent conditions revealed a reduced protease resistance of the atypical cases compared to the C-type cases. N terminal- specific antibodies bound to PrPres from H type but not from C or L type. The C-terminal-specific antibodies resulted in a shift in the glycoform profile and detected a fourth band in the Canadian H-type BSE.
Discussion: The C, L and H type BSE cases in Canada exhibit molecular characteristics similar to those described for classical and atypical BSE cases from Europe and Japan. This supports the theory that the importation of BSE contaminated feedstuff is the source of C-type BSE in Canada. *** It also suggests a similar cause or source for atypical BSE in these countries.
http://www.prion2009.com/sites/default/files/Prion2009_Book_of_Abstracts.pdf
Saturday, July 23, 2011
CATTLE HEADS WITH TONSILS, BEEF TONGUES, SPINAL CORD, SPECIFIED RISK MATERIALS (SRM's) AND PRIONS, AKA MAD COW DISEASE
http://transmissiblespongiformencephalopathy.blogspot.com/2011/07/cattle-heads-with-tonsils-beef-tongues.html
Saturday, November 6, 2010
TAFS1 Position Paper on Position Paper on Relaxation of the Feed Ban in the EU Berne, 2010 TAFS
INTERNATIONAL FORUM FOR TRANSMISSIBLE ANIMAL DISEASES AND FOOD SAFETY a non-profit Swiss Foundation
http://madcowfeed.blogspot.com/2010/11/tafs1-position-paper-on-position-paper.html
Archive Number 20101206.4364 Published Date 06-DEC-2010 Subject PRO/AH/EDR> Prion disease update 2010 (11)
PRION DISEASE UPDATE 2010 (11)
http://www.promedmail.org/direct.php?id=20101206.4364
October 2009
O.11.3
Infectivity in skeletal muscle of BASE-infected cattle
Silvia Suardi1, Chiara Vimercati1, Fabio Moda1, Ruggerone Margherita1, Ilaria Campagnani1, Guerino Lombardi2, Daniela Gelmetti2, Martin H. Groschup3, Anne Buschmann3, Cristina Casalone4, Maria Caramelli4, Salvatore Monaco5, Gianluigi Zanusso5, Fabrizio Tagliavini1 1Carlo Besta" Neurological Institute,Italy; 2IZS Brescia, Italy; 33FLI Insel Riems, D, Germany; 4CEA-IZS Torino, Italy; 5University of Verona, Italy
Background: BASE is an atypical form of bovine spongiform encephalopathy caused by a prion strain distinct from that of BSE. Upon experimental transmission to cattle, BASE induces a previously unrecognized disease phenotype marked by mental dullness and progressive atrophy of hind limb musculature. Whether affected muscles contain infectivity is unknown. This is a critical issue since the BASE strain is readily transmissible to a variety of hosts including primates, suggesting that humans may be susceptible.
Objectives: To investigate the distribution of infectivity in peripheral tissues of cattle experimentally infected with BASE. Methods: Groups of Tg mice expressing bovine PrP (Tgbov XV, n= 7-15/group) were inoculated both i.c. and i.p. with 10% homogenates of a variety of tissues including brain, spleen, cervical lymph node, kidney and skeletal muscle (m. longissimus dorsi) from cattle intracerebrally infected with BASE. No PrPres was detectable in the peripheral tissues used for inoculation either by immunohistochemistry or Western blot.
Results: Mice inoculated with BASE-brain homogenates showed clinical signs of disease with incubation and survival times of 175±15 and 207±12 days. Five out of seven mice challenged with skeletal muscle developed a similar neurological disorder, with incubation and survival times of 380±11 and 410±12 days. At present (700 days after inoculation) mice challenged with the other peripheral tissues are still healthy. The neuropathological phenotype and PrPres type of the affected mice inoculated either with brain or muscle were indistinguishable and matched those of Tgbov XV mice infected with natural BASE.
Discussion: Our data indicate that the skeletal muscle of cattle experimentally infected with BASE contains significant amount of infectivity, at variance with BSE-affected cattle, raising the issue of intraspecies transmission and the potential risk for humans. Experiments are in progress to assess the presence of infectivity in skeletal muscles of natural BASE.
http://www.prion2009.com/sites/default/files/Prion2009_Book_of_Abstracts.pdf
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.
http://ww2.isid.org/Downloads/14th_ICID_ISE_Abstracts.pdf
STRICTLY PRIVATE AND CONFIDENTIAL 25, AUGUST 1995
snip...
To minimise the risk of farmers' claims for compensation from feed compounders.
To minimise the potential damage to compound feed markets through adverse publicity.
To maximise freedom of action for feed compounders, notably by maintaining the availability of meat and bone meal as a raw material in animal feeds, and ensuring time is available to make any changes which may be required.
snip...
THE FUTURE
4..........
MAFF remains under pressure in Brussels and is not skilled at handling potentially explosive issues.
5. Tests _may_ show that ruminant feeds have been sold which contain illegal traces of ruminant protein. More likely, a few positive test results will turn up but proof that a particular feed mill knowingly supplied it to a particular farm will be difficult if not impossible.
6. The threat remains real and it will be some years before feed compounders are free of it. The longer we can avoid any direct linkage between feed milling _practices_ and actual BSE cases, the more likely it is that serious damage can be avoided. ...
SEE full text ;
http://web.archive.org/web/20060517074958/http://www.bseinquiry.gov.uk/files/yb/1995/08/24002001.pdf
2011
Monday, September 26, 2011
L-BSE BASE prion and atypical sporadic CJD
http://bse-atypical.blogspot.com/2011/09/l-bse-base-prion-and-atypical-sporadic.html
Monday, May 23, 2011
Atypical Prion Diseases in Humans and Animals 2011 Top Curr Chem (2011)
DOI: 10.1007/128_2011_161
# Springer-Verlag Berlin Heidelberg 2011
Atypical Prion Diseases in Humans and Animals
Michael A. Tranulis, Sylvie L. Benestad, Thierry Baron, and Hans Kretzschmar
Abstract
Although prion diseases, such as Creutzfeldt–Jakob disease (CJD) in humans and scrapie in sheep, have long been recognized, our understanding of their epidemiology and pathogenesis is still in its early stages. Progress is hampered by the lengthy incubation periods and the lack of effective ways of monitoring and characterizing these agents. Protease-resistant conformers of the prion protein (PrP), known as the “scrapie form” (PrPSc), are used as disease markers, and for taxonomic purposes, in correlation with clinical, pathological, and genetic data. In humans, prion diseases can arise sporadically (sCJD) or genetically (gCJD and others), caused by mutations in the PrP-gene (PRNP), or as a foodborne infection, with the agent of bovine spongiform encephalopathy (BSE) causing variant CJD (vCJD). Person-to-person spread of human prion disease has only been known to occur following cannibalism (kuru disease in Papua New Guinea) or through medical or surgical treatment (iatrogenic CJD, iCJD). In contrast, scrapie in small ruminants and chronic wasting disease (CWD) in cervids behave as infectious diseases within these species. Recently, however, so-called atypical forms of prion diseases have been discovered in sheep (atypical/Nor98 scrapie) and in cattle, BSE-H and BSE-L. These maladies resemble sporadic or genetic human prion diseases and might be their animal equivalents. This hypothesis also raises the significant public health question of possible epidemiological links between these diseases and their counterparts in humans.
M.A. Tranulis (*)
Norwegian School of Veterinary Science, Oslo, Norway
e-mail: Michael.Tranulis@nvh.no
S.L. Benestad
Norwegian Veterinary Institute, Oslo, Norway
T. Baron
Agence Nationale de Se´curite´ Sanitaire, ANSES, Lyon, France
H. Kretzschmar
Ludwig–Maximilians University of Munich, Munich, Germany
Keywords Animal Atypical Atypical/Nor98 scrapie BSE-H BSE-L Human Prion disease Prion strain Prion type
http://resources.metapress.com/pdf-preview.axd?code=f433r34h34ugg617&size=largest
see full text and more here ;
http://bse-atypical.blogspot.com/2011/05/atypical-prion-diseases-in-humans-and.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
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
Monday, April 25, 2011
Experimental Oral Transmission of Atypical Scrapie to Sheep
Volume 17, Number 5-May 2011
http://nor-98.blogspot.com/2011/04/experimental-oral-transmission-of.html
Thursday, June 2, 2011
USDA scrapie report for April 2011 NEW ATYPICAL NOR-98 SCRAPIE CASES Pennsylvania AND California
http://nor-98.blogspot.com/2011/06/usda-scrapie-report-for-april-2011-new.html
Monday, June 20, 2011 2011
Annual Conference of the National Institute for Animal Agriculture ATYPICAL NOR-98 LIKE SCRAPIE UPDATE USA
http://nor-98.blogspot.com/2011/06/2011-annual-conference-of-national.html
Thursday, July 14, 2011
Histopathological Studies of "CH1641-Like" Scrapie Sources Versus Classical Scrapie and BSE Transmitted to Ovine Transgenic Mice (TgOvPrP4)
http://transmissiblespongiformencephalopathy.blogspot.com/2011/07/histopathological-studies-of-ch1641.html
Wednesday, October 12, 2011
White-tailed deer are susceptible to the agent of sheep scrapie by intracerebral inoculation
http://chronic-wasting-disease.blogspot.com/2011/10/white-tailed-deer-are-susceptible-to.html
Monday, November 14, 2011
WYOMING Creutzfeldt Jakob Disease, CWD, TSE, PRION REPORTING 2011
http://transmissiblespongiformencephalopathy.blogspot.com/2011/11/wyoming-creutzfeldt-jakob-disease-cwd.html
UPDATED DATA ON 2ND CWD STRAIN
Wednesday, September 08, 2010
CWD PRION CONGRESS SEPTEMBER 8-11 2010
http://chronic-wasting-disease.blogspot.com/2010/09/cwd-prion-2010.html
Wednesday, January 5, 2011
ENLARGING SPECTRUM OF PRION-LIKE DISEASES Prusiner Colby et al 2011
Prions
David W. Colby1,* and Stanley B. Prusiner1,2
http://betaamyloidcjd.blogspot.com/2011/01/enlarging-spectrum-of-prion-like.html
Wednesday, November 09, 2011
Case report Sporadic fatal insomnia in a young woman: A diagnostic challenge: Case Report TEXAS
HOW TO TURN A POTENTIAL MAD COW VICTIM IN THE USA, INTO A HAPPENSTANCE OF BAD LUCK, A SPONTANEOUS MUTATION FROM NOTHING.
OR WAS IT $$$
http://creutzfeldt-jakob-disease.blogspot.com/2011/11/case-report-sporadic-fatal-insomnia-in.html
Tuesday, November 08, 2011
Can Mortality Data Provide Reliable Indicators for Creutzfeldt-Jakob Disease Surveillance? A Study in France from 2000 to 2008 Vol. 37, No. 3-4, 2011
Original Paper
Conclusions:These findings raise doubt about the possibility of a reliable CJD surveillance only based on mortality data.
http://creutzfeldt-jakob-disease.blogspot.com/2011/11/can-mortality-data-provide-reliable.html
U.S.A. HIDING MAD COW DISEASE VICTIMS AS SPORADIC CJD ? (see video at bottom)
http://creutzfeldt-jakob-disease.blogspot.com/2009/07/usa-hiding-mad-cow-disease-victims-as.html
2006
USA sporadic CJD cases rising ;
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
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
CJD USA RISING, with UNKNOWN PHENOTYPE ;
5 Includes 41 cases in which the diagnosis is pending, and 17 inconclusive cases;
*** 6 Includes 46 cases with type determination pending in which the diagnosis of vCJD has been excluded.
http://www.cjdsurveillance.com/pdf/case-table.pdf
Thursday, August 4, 2011
Terry Singeltary Sr. on the Creutzfeldt-Jakob Disease Public Health Crisis, Date aired: 27 Jun 2011 (SEE VIDEO)
http://transmissiblespongiformencephalopathy.blogspot.com/2011/08/terry-singeltary-sr-on-creutzfeldt.html
Sunday, August 21, 2011
The British disease, or a disease gone global, The TSE Prion Disease (SEE VIDEO)
http://transmissiblespongiformencephalopathy.blogspot.com/2011/08/british-disease-or-disease-gone-global.html
Saturday, March 5, 2011
MAD COW ATYPICAL CJD PRION TSE CASES WITH CLASSIFICATIONS PENDING ON THE RISE IN NORTH AMERICA
http://transmissiblespongiformencephalopathy.blogspot.com/2011/03/mad-cow-atypical-cjd-prion-tse-cases.html
Friday, November 04, 2011
Diagnostic accuracy of cerebrospinal fluid protein markers for sporadic Creutzfeldt-Jakob disease in Canada: a 6-year prospective study Research article
http://creutzfeldt-jakob-disease.blogspot.com/2011/11/diagnostic-accuracy-of-cerebrospinal.html
WHO WILL FOLLOW THE CHILDREN FOR CJD SYMPTOMS ???
Saturday, May 2, 2009
U.S. GOVERNMENT SUES WESTLAND/HALLMARK MEAT OVER USDA CERTIFIED DEADSTOCK DOWNER COW SCHOOL LUNCH PROGRAM
http://downercattle.blogspot.com/2009/05/us-government-sues-westlandhallmark.html
http://downercattle.blogspot.com/
Friday, November 18, 2011
country-of-origin labeling law (COOL) violates U.S. obligations under WTO rules WT/DS384/R WT/DS386/R
http://naiscoolyes.blogspot.com/2011/11/country-of-origin-labeling-law-cool.html
Thursday, November 17, 2011
International cattle ID and traceability: Competitive implications for the US
Food Policy Volume 37, Issue 1, February 2012, Pages 31-40
http://naiscoolyes.blogspot.com/2011/11/international-cattle-id-and.html
Tuesday, November 15, 2011
Alternative BSE Risk Assessment Methodology of Imported Beef and Beef Offal to Japan Journal of Veterinary Medical Science
Advance Publication
http://transmissiblespongiformencephalopathy.blogspot.com/2011/11/alternative-bse-risk-assessment.html
TSS
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