Volume 17, Number 9–September 2011
Research
Classical Bovine Spongiform Encephalopathy by Transmission of H-Type Prion in Homologous Prion Protein Context
Juan-María Torres, Olivier Andréoletti, Caroline Lacroux, Irene Prieto, Patricia Lorenzo, Magdalena Larska, Thierry Baron, and Juan-Carlos Espinosa Author affiliations: Centro de Investigación en Sanidad Animal, Madrid, Spain (J.-M. Torres, I. Prieto, P. Lorenzo, M. Larska, J.-C. Espinosa); Ecole Nationale Vétérinaire de Toulouse, Toulouse, France (O. Andréoletti, C. Lacroux); and Agence Francaise de Sécurité Sanitaire des Aliments, Lyon, France (T. Baron)
Abstract
Bovine spongiform encephalopathy (BSE) and BSE-related disorders have been associated with a single major prion strain. Recently, 2 atypical, presumably sporadic forms of BSE have been associated with 2 distinct prion strains that are characterized mainly by distinct Western blot profiles of abnormal protease-resistant prion protein (PrPres), named high-type (BSE-H) and low-type (BSE-L), that also differed from classical BSE. We characterized 5 atypical BSE-H isolates by analyzing their molecular and neuropathologic properties during transmission in transgenic mice expressing homologous bovine prion protein. Unexpectedly, in several inoculated animals, strain features emerged that were highly similar to those of classical BSE agent. These findings demonstrate the capability of an atypical bovine prion to acquire classical BSE–like properties during propagation in a homologous bovine prion protein context and support the view that the epidemic BSE agent could have originated from such a cattle prion.
snip...
Transmissible spongiform encephalopathies, or prion diseases, are a group of neurodegenerative disorders that include Creutzfeldt-Jakob disease (CJD) in humans, scrapie in sheep and goats, and bovine spongiform encephalopaty (BSE) in cattle. Prion diseases are characterized by specific histopathologic lesions and deposits of an abnormal conformational isoform (PrPSc) of the host-encoded physiologic prion protein (PrPC) in the central nervous system. PrPSc but not PrPC is partially resistant to digestion by proteinase K, resulting in an N terminally truncated prion protein termed PrPres that can be detected by Western blot and showing a characteristic banding pattern that reflects the 3 PrPres glycoforms. The apparent molecular masses and relative quantities of these glycoforms are used in biochemical PrPres typing as the criteria to differentiate between prion diseases.
BSE is a prion epidemic that has caused the deaths of ˜200,000 cattle in Europe, mainly in the United Kingdom, since it emerged in 1985. Although multiple agent strains have been identified in sheep scrapie (1,2) and human CJD (3,4), early evidence showed that BSE was caused by a single major strain (5,6) with the ability to efficiently cross the species barriers and showing stable features even when transmitted to other species. Transmission of BSE to humans through contaminated food is believed to be responsible for variant CJD (vCJD) (7,8). Several authors reported that BSE and vCJD prions share similar strain-specific features, including a unique PrPres molecular signature (6,9,10), after transmission to mice or macaques. However, other studies described the production of different PrPres molecular signature after BSE and vCJD prions transmission in wild-type (11) and human PrP transgenic mice (12,13).
Epidemiologic investigations identified contaminated meat and bone meal as the vehicle that recycled the BSE agent in the cattle population (14). However, the origin of BSE remains under debate, and the disease has been hypothesized to have derived either from sheep scrapie or from a spontaneous bovine prion disease analogous to sporadic forms of CJD in human (15) or even from human transmissible spongiform encephalopathy (16).
More recently, 2 atypical forms of BSE have been identified in several European countries (17), Japan (18,19), the United States (20), and Canada (21). Several studies suggest that these atypical disorders are associated with 2 distinct prion strains that are mainly characterized by distinct PrPres profiles, named high-type (H-type) and low-type (L-type) according to the electrophoretic migration of the unglycosylated PrPres, which is higher (BSE-H) or lower (BSE-L) than classical BSE (BSE-C) (22). An additional distinctive signature of H-type and L-type PrPres is the smaller proportion of the diglycosylated PrPres compared with the classical-type (C-type) PrPres, more obvious in L-type BSE (23–25).
All epidemiologic and biologic evidence strongly suggests that BSE-H and BSE-L represent sporadic forms of BSE (23,24) associated with 2 distinct prion strains. Transmission experiments in different mouse models, including transgenic mice expressing bovine PrP, showed that BSE-H and BSE-L exhibited strain-specific features clearly distinct between each other that also differed from BSE-C (13,25–28). However, BSE-L isolates unexpectedly showed transmission of a disease with some phenotypic features that resembled those of the BSE-C agent when inoculated in either transgenic mice expressing ovine PrP (28) or inbred wild-type mouse lines (25), suggesting that atypical bovine strains can modify their properties, at least after species barrier passages, converging with those of BSE-C.
We show that the transmission of atypical BSE-H isolates in transgenic mice expressing homologous bovine prion protein (PrP) led to emergence of a clearly distinct prion with strain features similar to those of the BSE-C agent and that such similarities were maintained on subsequent passages. These observations provide new insights into the nature of the events that could have led to the BSE epizootic.
Materials and Methods
snip...
Discussion
We studied the behavior and stability of the atypical BSE-H during propagation into a bovine PrP background, thus in the absence of a species barrier. We used Tg110 mice (29,36) because they express a PrPC homologous to that of the donors, thus providing a relevant context for comparing atypical BSE-H and epizootic BSE-C isolates.
Our results showed that all BSE-H isolates induced a typical neurologic disease on primary transmission, with a 100% attack rate and survival times similar to those produced by several BSE-C isolates in this mouse line (29,36) (Figure 1). The longer survival times for some mice infected with BSE-H isolates could reflect a lower infectivity of this isolate consistent with the reduction of survival time observed on subpassages, approaching that for BSE-C or BSE-H isolates of presumably higher titer (i.e., producing no substantial reduction of survival time on subpassage). These results are also consistent with another comparative study of BSE-H and BSE-C transmissions in a different bovine PrP mouse line (27). These data suggest that atypical BSE-H and BSE-C agents have similar transmission features into Tg110 mice.
Although all BSE-H–inoculated mice showed homogeneous survival times, a phenotypic divergence was observed in a few animals infected with 2 of the BSE-H isolates. Surprisingly, these few mice showed phenotypic features clearly distinct from those in most of the BSE-H–infected mice but similar to those of BSE-C propagated onto the same mice, according to various criteria. First, a PrPres profile indistinguishable from that produced by BSE-C agent in these mice but clearly distinct from that of BSE-H in cattle, in terms of 1) apparent molecular mass of PrPres, 2) PrPres glycosylation pattern, 3) immunoreactivity with 12B2 mAb, and 4) pattern of labeling with Saf84 antibody. Second, the vacuolation profile essentially overlapped that in mice infected with BSE-C, with slight differences only in the mesencephalic tegmentum area. Third, the spatial distribution of PrPres in the brain was clearly similar to that of mice infected with BSE-C. Fourth, PrPSc was consistently detected in the spleen, similar to mice infected with BSE-C. These similarities with BSE-C were fully retained after a second passage by using brain homogenate from mice with C-like features, whereas a BSE-H strain phenotype was maintained in mice inoculated with mouse brains homogenates containing H-type PrPres.
However, C-like features emerged in only 2 of the 5 isolates tested. Because only a low proportion of the mice inoculated with these 2 isolates exhibited these novel features (3/12 and 2/10, respectively), the lack of such observation in the other 3 isolates, and in 2 other independent studies of 3 BSE-H isolates in different bovine transgenic mouse lines (27), could be due to the low number of inoculated mice (6 per isolate), which could be statistically insufficient for such an event. No variability was ever observed in the PrPres profiles of >100 Tg110 mice inoculated with 4 different BSE-C isolates (29,36) (Figure 1). However, a divergent evolution of the BSE agent has been reported after trans-species transmission in both wild-type (11) and human PrP transgenic mice (12,39,40).
Although further studies are required to clarify the mechanisms associated with the emergence of distinct phenotypes among individual mice, several factors would be expected to influence the probability of detecting such a variant through mouse bioassay. These factors are 1) amount or regions of cattle brain tissue taken for inoculum preparation, 2) physicochemical treatment during inoculum preparation (e.g., temperature, homogenization buffer), 3) the precise site of mouse inoculation, 4) the infectious titer of the inoculum, and 5) others unknown mouse factor affecting prion propagation and disease evolution. Because samples used in this study were prepared from the same region (brainstem) following the same precise protocol and under identical conditions, differences in inoculum preparation and conditions are unlikely. However, the possibility that the observations might be influenced by the precise neuroanatomic origin of the inoculated bovine brainstem homogenate or by other mouse bioassay–related factors cannot be excluded.
The possible cross-contamination of the BSE-H isolates material (02-2695 and 45 from 2 laboratories in different countries) by a BSE-C infectious source was judged highly improbable for several reasons. These reasons are 1) the strict biosafety procedures followed for sample collection, preparation of the inocula, inoculation scheme, and care of mice; 2) the absence of C-type PrPSc in the BSE-H inocula used for transmissions as deduced by Western blot analysis; and 3) 2 independent transmission experiments, involving separate batches of both incriminated isolates, all produced consistent results.
Together, these observations support 2 possible hypotheses. First, a minor strain component might be present in BSE-H isolates that could emerge on subsequent transmission in Tg110 mice. Second, a new strain component has been generated during propagation of BSE-H agent in Tg110. In both instances, emergence of the new strain, either in the original cattle or during propagation in Tg110 mice, could be promoted by specific propagation conditions or by physicochemical treatment of the inoculum. In this regard, acquisition of novel properties by a sporadic cattle transmissible spongiform encephalopathy agent by a physicochemical treatment, such as that applied to carcass-derived products, has been invoked as a possible origin for the BSE epidemic (7).
Contrary to BSE-H, the atypical BSE-L agent retained unique and distinct phenotypic features, compared with BSE-C agent, on transmission to both bovine and human PrP transgenic mice (26–28). This agent, however, acquired phenotypic traits intriguingly similar to those of the BSE agent during trans-species transmission in either transgenic mice expressing ovine PrP (28) or inbred mouse lines. On the basis of these observations, the BSE-C agent already has been speculated to have originated from atypical BSE-L after conversion in an intermediate host such as a sheep. However, the capacity of these BSE-L–derived agents to retain BSE phenotypic traits after reinoculation to bovine PrP transgenic mice is a key question, remaining to be demonstrated, to show whether the observed convergence truly reflects a permanent strain shift of the BSE-L agent rather than a phenotypic convergence in an experimental model.
In contrast, our results suggest that prion strain divergence might occur on propagation of atypical BSE-H in a homologous bovine PrP context and that this strain divergence could result from a permanent strain shift of the BSE-H agent toward a C-like agent that is stable in subsequent passages. These findings emphasize the potential capacity of prion diversification during propagation, even in the absence of any species barrier, and represent an experimental demonstration of the capability of an atypical, presumably sporadic, bovine prion to acquire C-like properties during propagation in a homologous bovine PrP context.
Results in transgenic mouse models cannot be directly extrapolated to the natural host. However, our observations are consistent with the view that the BSE agent could have originated from a cattle prion, such as BSE-H, and provide new insights into the nature of the events that could have led to the appearance of this agent.
This study was supported by grants from the European Union (CT2004-50657 and CT2004-023183) and from UK Food Standards Agency (M03043).
Dr Torres is the lead researcher scientist of the Prions Group at the Centro de Investigación en Sanidad Animal–Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria, Madrid, Spain. His research interests include prion strain characterization and evolution and the pathogenesis of prion diseases and their effects on human and animal health.
http://www.cdc.gov/eid/content/17/9/101403.htm
The EMBO Journal (2002) 21, 6358 - 6366 doi:10.1093/emboj/cdf653
Subject Categories: Neuroscience | Molecular Biology of Disease
BSE prions propagate as either variant CJD-like or sporadic CJD-like prion strains in transgenic mice expressing human prion protein
Emmanuel A. Asante1, Jacqueline M. Linehan1, Melanie Desbruslais1, Susan Joiner1, Ian Gowland1, Andrew L. Wood1, Julie Welch1, Andrew F. Hill1, Sarah E. Lloyd1, Jonathan D.F. Wadsworth1 and John Collinge1 1.MRC Prion Unit and Department of Neurodegenerative Disease, Institute of Neurology, University College, Queen Square, London WC1N 3BG, UK
Correspondence to:
John Collinge, E-mail: j.collinge@prion.ucl.ac.uk
Received 1 August 2002; Accepted 17 October 2002; Revised 24 September 2002
--------------------------------------------------------------------------------
Abstract
Variant Creutzfeldt–Jakob disease (vCJD) has been recognized to date only in individuals homozygous for methionine at PRNP codon 129. Here we show that transgenic mice expressing human PrP methionine 129, inoculated with either bovine spongiform encephalopathy (BSE) or variant CJD prions, may develop the neuropathological and molecular phenotype of vCJD, consistent with these diseases being caused by the same prion strain. Surprisingly, however, BSE transmission to these transgenic mice, in addition to producing a vCJD-like phenotype, can also result in a distinct molecular phenotype that is indistinguishable from that of sporadic CJD with PrPSc type 2. These data suggest that more than one BSE-derived prion strain might infect humans; it is therefore possible that some patients with a phenotype consistent with sporadic CJD may have a disease arising from BSE exposure.
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Keywords: BSE, Creutzfeldt–Jakob disease, prion, transgenic
http://www.nature.com/emboj/journal/v21/n23/full/7594869a.html
Tuesday, November 02, 2010
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
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
Over the next 8-10 weeks, approximately 40% of all the adult mink on the farm died from TME.
snip...
The rancher was a ''dead stock'' feeder using mostly (>95%) downer or dead dairy cattle...
http://web.archive.org/web/20030516051623/http://www.bseinquiry.gov.uk/files/mb/m09/tab05.pdf
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
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
Thursday, July 21, 2011
A Second Case of Gerstmann-Sträussler-Scheinker Disease Linked to the G131V Mutation in the Prion Protein Gene in a Dutch Patient Journal of Neuropathology & Experimental Neurology:
August 2011 - Volume 70 - Issue 8 - pp 698-702
http://transmissiblespongiformencephalopathy.blogspot.com/2011/07/second-case-of-gerstmann-straussler.html
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
Wednesday, June 15, 2011
Galveston, Texas - Isle port moves through thousands of heifers headed to Russia, none from Texas, Alabama, or Washington, due to BSE risk factor
http://transmissiblespongiformencephalopathy.blogspot.com/2011/06/galveston-texas-isle-port-moves-through.html
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/pls/apex/f?p=2400:1001:5492868805159684::NO::F2400_P1001_BACK_PAGE,F2400_P1001_PUB_MAIL_ID:1000,86129
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
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
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
Thursday, July 28, 2011
An Update on the Animal Disease Traceability Framework July 27, 2011
http://naiscoolyes.blogspot.com/2011/07/update-on-animal-disease-traceability.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
Monday, August 8, 2011
Susceptibility of Domestic Cats to CWD Infection
http://felinespongiformencephalopathyfse.blogspot.com/2011/08/susceptibility-of-domestic-cats-to-cwd.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
Please see the following warning from CDC about prion TSE consumption in North America ;
Thursday, May 26, 2011
Travel History, Hunting, and Venison Consumption Related to Prion Disease Exposure, 2006-2007 FoodNet Population Survey
Journal of the American Dietetic Association Volume 111, Issue 6 , Pages 858-863, June 2011.
http://transmissiblespongiformencephalopathy.blogspot.com/2011/05/travel-history-hunting-and-venison.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 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, 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 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
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, August 12, 2011
Creutzfeldt-Jakob disease (CJD) biannual update (2011/2), Incidents Panel, National Anonymous Tonsil Archive
http://transmissiblespongiformencephalopathy.blogspot.com/2011/08/creutzfeldt-jakob-disease-cjd-biannual.html
Wednesday, June 29, 2011
TSEAC Meeting August 1, 2011 donor deferral Saudi Arabia vCJD risk blood and blood products
http://tseac.blogspot.com/2011/06/tseac-meeting-august-1-2011-donor.html
TSS
Sunday, August 21, 2011
Saturday, August 20, 2011
BSE PRION Terrestrial Animal Health - Policy & Procedures / Santé des animaux terrestres - politiques et procédures 2011-08-16
Bovine Spongiform Encephalopathy (BSE) Import Policy for Bovine Animals and Their Products and By-Products
http://www.inspection.gc.ca/english/anima/heasan/pol/ie-2005-9e.shtml
Amendment: Denmark and Panama added to the list of countries with negligible BSE risk.
Terrestrial Animal Health Import Requirements for Rendered Products and Inedible Products
http://www.inspection.gc.ca/english/anima/heasan/pol/ie-2002-10e.shtml
Amendments: Denmark and Panama added to list of countries with negligible BSE risk. Clarification on when a Questionnaire is needed.
==================================================
CANADA BSE
Friday, March 4, 2011
Alberta dairy cow found with mad cow disease
http://transmissiblespongiformencephalopathy.blogspot.com/2011/03/alberta-dairy-cow-found-with-mad-cow.html
==================================================
U.S.A. BSE ??? $$$
[Docket No. FSIS-2006-0011]
FSIS Harvard Risk Assessment of Bovine Spongiform Encephalopathy (BSE)
http://www.fsis.usda.gov/OPPDE/Comments/2006-0011/2006-0011-1.pdf
Response to Public Comments on the Harvard Risk Assessment of Bovine Spongiform Encephalopathy Update, October 31, 2005 INTRODUCTION The United States Department of Agriculture’s Food Safety and Inspection Service (FSIS) held a public meeting on July 25, 2006 in Washington, D.C. to present findings from the Harvard Risk Assessment of Bovine Spongiform Encephalopathy Update, October 31, 2005 (report and model located on the
FSIS website:
http://www.fsis.usda.gov/Science/Risk_Assessments/index.asp).
Comments on technical aspects of the risk assessment were then submitted to FSIS.
Comments were received from Food and Water Watch, Food Animal Concerns Trust (FACT), Farm Sanctuary, R-CALF USA, Linda A Detwiler, and Terry S. Singeltary.
This document provides itemized replies to the public comments received on the 2005 updated Harvard BSE risk assessment. Please bear the following points in mind:
http://www.fsis.usda.gov/PDF/BSE_Risk_Assess_Response_Public_Comments.pdf
Owens, Julie From: Terry S. Singeltary Sr. [flounder9@verizon.net]
Sent: Monday, July 24, 2006 1:09 PM To: FSIS RegulationsComments
Subject: [Docket No. FSIS-2006-0011] FSIS Harvard Risk Assessment of Bovine Spongiform Encephalopathy (BSE) Page 1 of 98 8/3/2006
Greetings FSIS, I would kindly like to comment on the following ;
http://www.fsis.usda.gov/OPPDE/Comments/2006-0011/2006-0011-1.pdf
Suppressed peer review of Harvard study October 31, 2002.
October 31, 2002 Review of the Evaluation of the Potential for Bovine Spongiform Encephalopathy in the United States Conducted by the Harvard Center for Risk Analysis, Harvard School of Public Health and Center for Computational Epidemiology, College of Veterinary Medicine, Tuskegee University Final Report Prepared for U.S. Department of Agriculture Food Safety and Inspection Service Office of Public Health and Science Prepared by RTI Health, Social, and Economics Research Research Triangle Park, NC 27709 RTI Project Number 07182.024
http://www.fsis.usda.gov/oa/topics/BSE_Peer_Review.pdf
Sunday, February 14, 2010
[Docket No. FSIS-2006-0011] FSIS Harvard Risk Assessment of Bovine Spongiform Encephalopathy (BSE)
http://bseusa.blogspot.com/2010/02/docket-no-fsis-2006-0011-fsis-harvard.html
----- Original Message -----
From: Terry S. Singeltary Sr.
To: Debra.Beasley@aphis.usda.gov
Sent: Tuesday, November 24, 2009 11:01 AM
Subject: OIE has recently published its proposed animal welfare guidelines for public comment
Greetings USDA/APHIS et al,
I would kindly like to comment on OIE proposed guidelines.
AS I said before, OIE should hang up there jock strap now, since it appears they will buckle every time a country makes some political hay about trade protocol, commodities and futures. IF they are not going to be science based, they should do everyone a favor and dissolve there organization. THE reason most every country around the globe came down with BSE/TSE in their cattle, were due to the failed and flawed BSE/TSE testing and surveillance policy of the O.I.E. NOW, they don't even acknowledge atypical scrapie it seems, as one for concern $
Monday, November 23, 2009
BSE GBR RISK ASSESSMENTS UPDATE NOVEMBER 23, 2009 COMMISSION OF THE EUROPEAN COMMUNITIES AND O.I.E.
http://docket-aphis-2006-0041.blogspot.com/2009/11/bse-gbr-risk-assessments-update.html
Tuesday, May 24, 2011 2:24 PM
O.I.E. Terrestrial Animal Health Standards Commission and prion (TSE) disease reporting 2011
http://transmissiblespongiformencephalopathy.blogspot.com/2011/05/oie-terrestrial-animal-health-standards.html
Saturday, June 19, 2010 U.S.
DENIED UPGRADED BSE STATUS FROM OIE
http://usdameatexport.blogspot.com/2010/06/us-denied-upgraded-bse-status-from-oie.html
IN A NUT SHELL ; $$$
(Adopted by the International Committee of the OIE on 23 May 2006)
11. Information published by the OIE is derived from appropriate declarations made by the official Veterinary Services of Member Countries.The OIE is not responsible for inaccurate publication of country disease status based on inaccurate information or changes in epidemiological status or other significant events that were not promptly reported to then Central Bureau............
http://www.oie.int/eng/Session2007/RF2006.pdf
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/pls/apex/f?p=2400:1001:5492868805159684::NO::F2400_P1001_BACK_PAGE,F2400_P1001_PUB_MAIL_ID:1000,86129
Scientific Report of the European Food Safety Authority on the Assessment of the Geographical BSE Risk (GBR) of the USA Question number: EFSA-Q-2003-083
Adopted: 1 July 2004
Summary
The European Food Safety Authority and its Scientific Expert Working Group on the Assessment of the Geographical Bovine Spongiform Encephalopathy (BSE) Risk (GBR) were asked by the European Commission (EC) to provide an up-to-date scientific report on the GBR in the United States of America, i.e. the likelihood of the presence of one or more cattle being infected with BSE, pre-clinically as well as clinically, in USA. This scientific report addresses the GBR of USA as assessed in 2004 based on data covering the period 1980-2003.
The BSE agent was probably imported into USA and could have reached domestic cattle in the middle of the eighties. These cattle imported in the mid eighties could have been rendered in the late eighties and therefore led to an internal challenge in the early nineties. It is possible that imported meat and bone meal (MBM) into the USA reached domestic cattle and leads to an internal challenge in the early nineties.
A processing risk developed in the late 80s/early 90s when cattle imports from BSE risk countries were slaughtered or died and were processed (partly) into feed, together with some imports of MBM. This risk continued to exist, and grew significantly in the mid 90’s when domestic cattle, infected by imported MBM, reached processing. Given the low stability of the system, the risk increased over the years with continued imports of cattle and MBM from BSE risk countries.
EFSA concludes that the current GBR level of USA is III, i.e. it is likely but not confirmed that domestic cattle are (clinically or pre-clinically) infected with the BSE-agent. As long as there are no significant changes in rendering or feeding, the stability remains extremely/very unstable. Thus, the probability of cattle to be (pre-clinically or clinically) infected with the BSE-agent persistently increases.
http://www.efsa.europa.eu/EFSA/efsa_locale-1178620753812_1211902594180.htm
Annex to the EFSA Scientific Report (2004) 3, 1-17 on the Assessment of the Geographical BSE Risk of USA - 1 - European Food Safety Authority Scientific Expert Working Group on GBR Working Group Report on the Assessment of the Geographical BSE-Risk (GBR) of UNITED STATES OF AMERICA 2004
Annex to the EFSA Scientific Report (2004) 3, 1-17 on the Assessment of the Geographical BSE Risk of USA - 7 - 2.3
Overall assessment of the external challenge
The level of the external challenge that has to be met by the BSE/cattle system is estimated according to the guidance given by the SSC in its final opinion on the GBR of July 2000 (as updated in January 2002). Live cattle imports: In total the country imported 2038 (other sources) or 1128 (CD) live cattle from BSE risk countries other than Canada, of which 327 (other sources) or 323 (CD) came from the UK. From Canada the imports were >500,000 animals per year. The numbers shown in table 1 are the raw import figures and are not reflecting the adjusted imports for the assessment of the external challenge. Broken down to 5 year periods the resulting external challenge is as given in table 3. This assessment takes into account the different aspects discussed above that allow to assume that certain imported cattle did not enter the domestic BSE-cattle system, i.e. were not rendered into feed. In the case of the USA, all the animals for which tracing information showed that they were not rendered were excluded from the external challenge.
MBM imports:
In total the country imported 689 tons MBM (CD) or 2,230 tons MBM (other sources) from BSE risk countries other than Canada, of which 5 tons (CD) or 101 tons (other sources) were exported from the UK (UK export data). From Canada, the imports were about 30 000 tons per year. The numbers shown in table 2 are the raw import figures and are not reflecting the adjusted imports for the assessment of the external challenge. Broken down to 5 year periods the resulting external challenge is as given in table 3. This assessment takes into account the different aspects discussed above that allow to assume that certain imported MBM did not enter the domestic BSE/cattle system or did not represent an external challenge for other reasons. As it was illegal to export mammalian MBM from UK since 27/03/1996, exports indicated after that date should only have included non-mammalian MBM. In the case of the USA imported MBM from UK in 1989 and between 1997 and 1999 was not taken into account.
Feeding Use of MBM in cattle feed • Until 1997 ruminant MBM (RMBM) could legally be included in cattle feed and was indeed commonly fed to cattle of different age and type. Prior to the feed ban the US authorities estimated that 10% of all MBM would deliberately have been fed to cattle. Feed bans • A ban to feed (several types of) MMBM to ruminants was put in place in August 1997. Derogation from the ban was granted for pure porcine and equine protein (MBM) coming from designated (single species) rendering plants. This MMBM might still be fed to cattle. Therefore this feed ban is a ruminant to ruminant ban. • It is planned to prohibit the use of all mammalian and poultry protein in ruminant feed and prohibiting materials from non-ambulatory disabled cattle and dead stock from use in all animal feed.
Conclusion on the ability to avoid recycling
• Before 1997, US system would not have been able to avoid recycling of the BSEagent to any measurable extent. If the BSE-agent was introduced into the feed chain, it could have reached cattle.
• After the introduction of the 1997 ban in August 1997, the ability to avoid recycling of BSE-infectivity was somewhat improved. However, the rendering of ruminant material (including SRM and fallen stock) is inadequate (non pressurized), and cross-contamination potentials of cattle feed with other feeds remain.
• Therefore, the system is still unable to avoid recycling of BSE-infectivity if already present in the system or incoming.
Feeding
Until August 1997, RMBM was legally fed to cattle. Feeding was therefore "not OK". In August 1997 an RMBM-ban was introduced but feeding of non-ruminant MBM to cattle remained legal as well as feeding of RMBM to non-ruminant animals (farm animals and pets). An RMBM ban is difficult to maintain, as only labels can distinguish the various MMBMs. This makes control of the feed ban very difficult because analytical differentiation between ruminant and non-ruminant MBM is difficult if not impossible.
Due to the highly specialised production system in the USA, various mammalian MBM streams can be separated. Such a feed ban would therefore be assessed as "reasonably OK", for all regions where this highly specialised system exists. However, several areas in the USA do have mixed farming and mixed feed mills, and in such regions an RMBM ban would not suffice. Additionally, official controls for cattle feeds to control for compliance with the ban started in 2002. Thus, for the whole country, the assessment of the feeding after 1997 remains "not OK", but improving.
Rendering
The rendering industry is operating with processes that are not known to reduce
infectivity. It is therefore concluded that rendering was and is "not OK".
SRM-removal
SRM were and are still rendered for feed, as are (parts of) the fallen stock. SRMremoval
is therefore regarded as "not OK".
BSE-surveillance
Before 1989, the ability of the system to identify (and eliminate) BSE-cases was
limited. Since 1990 this ability is improved, thanks to a specific (passive) BSE
surveillance. The initiated introduction of active surveillance in risk populations
should improve the system significantly.
On the basis of the available information, it has to be concluded that the country's
BSE/cattle system was extremely unstable until today, i.e., it would have recycled and
amplified BSE-infectivity very fast, should it have entered the system. The stability of
the BSE/cattle system in the USA overtime is as given in table 4.
The present assessment modifies the stability assessment of the previous GBR report
in 2000 mainly due to a different perception of the impact of BSE surveillance on
stability and of the efficiency of the RMBM feed ban.
Interaction of stability and external challenge in the USA
Period Stability External Challenge Internal challenge
1980 to
1985
1986 to
1990
Moderate Possibly present
1991 to 1995
Very high
1996 to
2000
2001 to
2003
Extremely unstable Extremely high Likely to be present and growing
5. CONCLUSION ON THE GEOGRAPHICAL BSE-RISK
5.1 The current GBR as function of the past stability and challenge
• The current geographical BSE risk (GBR) level is III, i.e. it is likely but not
confirmed that domestic cattle are (clinically or pre-clinically) infected with the
BSE-agent.
Note1: It is also worth noting that the current GBR conclusions are not dependent on
the large exchange of imports between USA and Canada. External challenge due to
exports to the USA from European countries varied from moderate to high. These
challenges indicate that it was likely that BSE infectivity was introduced into the
North American continent.
snip...please see full text ;
http://www.efsa.europa.eu/en/scdocs/doc/3rax1.pdf
HOWEVER, my files show 44 tons of greaves for USA. ...TSS
Subject: Re: exports from the U.K. of it's MBM to U.S.???
From: S.J.Pearsall@esg.maff.gsi.gov.uk
Date: Tue, 8 Feb 2000 14:03:16 +0000
To: flounder@wt.net (Receipt Notification Requested) (Non Receipt Notification Requested)
Terry Meat and bonemeal is not specifically classified for overseas trade purposes. The nearest equivalent is listed as flours and meals of meat or offals (including tankage), unfit for human consumption; greaves.
UK exports of this to the US are listed below:
Country Tonnes
1980
1981 12
1982
1983
1984 10
1985 2
1986
1987
1988
1989 20
1990
Data for exports between 1975 and 1979 are not readily available. These can be obtained (at a charge) from data retailers appointed by HM Customs and Excise: BTSL (Tel: 01372 463121) or Abacus (01245 252222).
Best wishes Simon Pearsall
Overseas trade statistics Stats (C&F)C
====================================== END...TSS
The most recent assessments (and reassessments) were published in June 2005 (Table I; 18), and included the categorisation of Canada, the USA, and Mexico as GBR III. Although only Canada and the USA have reported cases, the historically open system of trade in North America suggests that it is likely that BSE is present also in Mexico.
http://www.oie.int/boutique/extrait/06heim937950.pdf
PITUITARY EXTRACT
This was used to help cows super ovulate. This tissue was considered to be of greatest risk of containing BSE and consequently transmitting the disease...
http://collections.europarchive.org/tna/20090114081754/http://www.bseinquiry.gov.uk/files/yb/1988/06/08011001.pdf
NON-LICENSED HUMAN TISSUE DEVICES WERE NOT COMMERCIALLY AVAILABLE
snip...
I was quite prepared to believe in unofficial pituitary hormones, also in the 1970's, whether as described by Dr. Little, or in other circumstances, for animal use.
snip...
The fact that there were jars of pituitaries (or extract) around on shelves is attested by the still potent 1943 pituitaries, described in Stockell Hartree et al. (J/RF/17/291) which had come from the lab. at Mill Hill. Having taken the trouble to collect them, they were not lightly thrown out...
http://collections.europarchive.org/tna/20080102174454/http://www.bseinquiry.gov.uk/files/ws/s467bx.pdf
B.S.E. and Veterinary Medicines
Thank you very much indeed for your letter of the 26th of January outlining to me the various steps that are proposing to take in order to reduce the risk from B.S.E. in veterinary medicines. It is, as you say, and extremely difficult problem. ....
http://web.archive.org/web/20030526124448/http://www.bseinquiry.gov.uk/files/yb/1989/01/30008001.pdf
Draft cover letter to product licence holders (considered by Human and Vet Medicines including deer)
http://collections.europarchive.org/tna/20080103002832/http://www.bseinquiry.gov.uk/files/yb/1989/02/22008001.pdf
http://collections.europarchive.org/tna/20080102155758/http://www.bseinquiry.gov.uk/files/yb/1989/02/22011001.pdf
(It was noted with concern that hormone extracts could be manufactured by a veterinary surgeon for administration to animals under his care without any Medicines Act Control.)
PITUITARY EXTRACT
This was used to help cows super ovulate. This tissue was considered to be of greatest risk of containing BSE and consequently transmitting the disease.
BEEF BRAIN AND BRAIN INFUSION BROTHS
Considered to be of great risk.
http://collections.europarchive.org/tna/20080102164725/http://www.bseinquiry.gov.uk/files/yb/1988/06/08011001.pdf
COMMERCIAL IN CONFIDENCE
MEDICINES ACT - VETERINARY PRODUCTS COMMITTEE
5 BLANK PAGES. ...TSS
7. Any Other Business
http://collections.europarchive.org/tna/20080102164736/http://www.bseinquiry.gov.uk/files/yb/1988/06/07010001.pdf
TWA LITTLE STATEMENT 331
8 June 1988 Internal CVL meeting to discuss the implications of BSE to Biologicals Products containing bovine extracted material (Annex 6). (YB 88/06.08/11.1-11.2) Following a detailed review of situation the following recommendations were made:
1. Specific concern over use of pituitary gland products by veterinary surgeons and companies. Paper to be produced for Tolworth (Veterinary Medicines Division).
2. Urgent review of all products both immunological and pharmaceutical for possible inclusion of ingredients of bovine origin.
3. Draft guidelines to be presented in full to the National Office of Animal Health (NOAH), the trade body representing the Veterinary Medicines part of the pharmaceutical industry, at next meeting on 11 July 1988
http://collections.europarchive.org/tna/20080102163939/http://www.bseinquiry.gov.uk/files/ws/s331.pdf
TWA LITTLE minute
2. We have identified one problem over where we are unable to act and this is the use of gonadotrophins in embryo transfer work. Some veterinary surgeons are quite legally using this exemption from the Medicines Act contained in Section 9(2) to prepare gonadotrophins from pituitary glands from various species, including cattle. These hormones are used to stimulate superovulation in donor cows.
http://collections.europarchive.org/tna/20080102164806/http://www.bseinquiry.gov.uk/files/yb/1988/06/10001001.pdf
http://collections.europarchive.org/tna/20080102164811/http://www.bseinquiry.gov.uk/files/yb/1988/06/13010001.pdf
http://collections.europarchive.org/tna/20080103031215/http://www.bseinquiry.gov.uk/files/yb/1988/06/14006001.pdf
COMMERCIAL IN CONFIDENCE
3.2 Minute 5.3 - 5.4 Bovine Spongiform Encephalopathy
It was reported that some replies had been received from Companies using pituitary glands in their products. Copies of the BSE document had also been sent to DHSS and NIBSC.
and then another 3 + pages of blank space. ...TSS
http://collections.europarchive.org/tna/20080102164813/http://www.bseinquiry.gov.uk/files/yb/1988/09/06005001.pdf
COMMERCIAL IN CONFIDENCE
BSE - CURRENT POSITION WITH VETERINARY LICENCED PRODUCTS (MA.1968)
There are three areas of particular concern, vaccines (including emergency vaccines), pharmaceuticals which are covered by MA licences and unlicenses hormonal products produced under exemptions claimed under (Section 9(2) Medicines Act).
1) Vaccines
http://collections.europarchive.org/tna/20080103033809/http://www.bseinquiry.gov.uk/files/yb/1988/10/06005001.pdf
NOT FOR PUBLICATION
another 6 pages of blank space. ...TSS
http://collections.europarchive.org/tna/20080103032658/http://www.bseinquiry.gov.uk/files/yb/1988/11/01012001.pdf
http://collections.europarchive.org/tna/20080103032631/http://www.bseinquiry.gov.uk/files/yb/1988/11/04003001.pdf
http://collections.europarchive.org/tna/20080103033926/http://www.bseinquiry.gov.uk/files/yb/1988/04/00007001.pdf
COMMERCIAL IN CONFIDENCE
http://collections.europarchive.org/tna/20080103034137/http://www.bseinquiry.gov.uk/files/yb/1988/07/00007001.pdf
COMMERCIAL IN CONFIDENCE
Medicines Act - Veterinary Products Committee
http://collections.europarchive.org/tna/20080103034140/http://www.bseinquiry.gov.uk/files/yb/1988/09/00004001.pdf
COMMERCIAL IN CONFIDENCE
http://collections.europarchive.org/tna/20080102164744/http://www.bseinquiry.gov.uk/files/yb/1988/10/00003001.pdf
MANAGEMENT IN CONFIDENCE
CERTIFIED BSE-FREE HERDS FOR SOURCE OF MATERIAL FOR BIOLOGICAL PRODUCTS
http://collections.europarchive.org/tna/20080102184729/http://www.bseinquiry.gov.uk/files/yb/1989/01/04001001.pdf
Tuesday, February 8, 2011
U.S.A. 50 STATE BSE MAD COW CONFERENCE CALL Jan. 9, 2001
http://tseac.blogspot.com/2011/02/usa-50-state-bse-mad-cow-conference.html
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
Tuesday, November 02, 2010
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
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
Over the next 8-10 weeks, approximately 40% of all the adult mink on the farm died from TME.
snip...
The rancher was a ''dead stock'' feeder using mostly (>95%) downer or dead dairy cattle...
http://web.archive.org/web/20030516051623/http://www.bseinquiry.gov.uk/files/mb/m09/tab05.pdf
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
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
Thursday, July 21, 2011
A Second Case of Gerstmann-Sträussler-Scheinker Disease Linked to the G131V Mutation in the Prion Protein Gene in a Dutch Patient Journal of Neuropathology & Experimental Neurology:
August 2011 - Volume 70 - Issue 8 - pp 698-702
http://transmissiblespongiformencephalopathy.blogspot.com/2011/07/second-case-of-gerstmann-straussler.html
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
Wednesday, June 15, 2011
Galveston, Texas - Isle port moves through thousands of heifers headed to Russia, none from Texas, Alabama, or Washington, due to BSE risk factor
http://transmissiblespongiformencephalopathy.blogspot.com/2011/06/galveston-texas-isle-port-moves-through.html
Monday, May 30, 2011
CEPs for gelatin and impact of the revised EU Note for Guidance on the TSE risk EMEA/410/01 Rev.3) will come into force in July 2011
http://transmissiblespongiformencephalopathy.blogspot.com/2011/05/ceps-for-gelatin-and-impact-of-revised.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, August 12, 2011
Creutzfeldt-Jakob disease (CJD) biannual update (2011/2), Incidents Panel, National Anonymous Tonsil Archive
http://transmissiblespongiformencephalopathy.blogspot.com/2011/08/creutzfeldt-jakob-disease-cjd-biannual.html
Wednesday, June 29, 2011
TSEAC Meeting August 1, 2011 donor deferral Saudi Arabia vCJD risk blood and blood products
http://tseac.blogspot.com/2011/06/tseac-meeting-august-1-2011-donor.html
TSS
http://www.inspection.gc.ca/english/anima/heasan/pol/ie-2005-9e.shtml
Amendment: Denmark and Panama added to the list of countries with negligible BSE risk.
Terrestrial Animal Health Import Requirements for Rendered Products and Inedible Products
http://www.inspection.gc.ca/english/anima/heasan/pol/ie-2002-10e.shtml
Amendments: Denmark and Panama added to list of countries with negligible BSE risk. Clarification on when a Questionnaire is needed.
==================================================
CANADA BSE
Friday, March 4, 2011
Alberta dairy cow found with mad cow disease
http://transmissiblespongiformencephalopathy.blogspot.com/2011/03/alberta-dairy-cow-found-with-mad-cow.html
==================================================
U.S.A. BSE ??? $$$
[Docket No. FSIS-2006-0011]
FSIS Harvard Risk Assessment of Bovine Spongiform Encephalopathy (BSE)
http://www.fsis.usda.gov/OPPDE/Comments/2006-0011/2006-0011-1.pdf
Response to Public Comments on the Harvard Risk Assessment of Bovine Spongiform Encephalopathy Update, October 31, 2005 INTRODUCTION The United States Department of Agriculture’s Food Safety and Inspection Service (FSIS) held a public meeting on July 25, 2006 in Washington, D.C. to present findings from the Harvard Risk Assessment of Bovine Spongiform Encephalopathy Update, October 31, 2005 (report and model located on the
FSIS website:
http://www.fsis.usda.gov/Science/Risk_Assessments/index.asp).
Comments on technical aspects of the risk assessment were then submitted to FSIS.
Comments were received from Food and Water Watch, Food Animal Concerns Trust (FACT), Farm Sanctuary, R-CALF USA, Linda A Detwiler, and Terry S. Singeltary.
This document provides itemized replies to the public comments received on the 2005 updated Harvard BSE risk assessment. Please bear the following points in mind:
http://www.fsis.usda.gov/PDF/BSE_Risk_Assess_Response_Public_Comments.pdf
Owens, Julie From: Terry S. Singeltary Sr. [flounder9@verizon.net]
Sent: Monday, July 24, 2006 1:09 PM To: FSIS RegulationsComments
Subject: [Docket No. FSIS-2006-0011] FSIS Harvard Risk Assessment of Bovine Spongiform Encephalopathy (BSE) Page 1 of 98 8/3/2006
Greetings FSIS, I would kindly like to comment on the following ;
http://www.fsis.usda.gov/OPPDE/Comments/2006-0011/2006-0011-1.pdf
Suppressed peer review of Harvard study October 31, 2002.
October 31, 2002 Review of the Evaluation of the Potential for Bovine Spongiform Encephalopathy in the United States Conducted by the Harvard Center for Risk Analysis, Harvard School of Public Health and Center for Computational Epidemiology, College of Veterinary Medicine, Tuskegee University Final Report Prepared for U.S. Department of Agriculture Food Safety and Inspection Service Office of Public Health and Science Prepared by RTI Health, Social, and Economics Research Research Triangle Park, NC 27709 RTI Project Number 07182.024
http://www.fsis.usda.gov/oa/topics/BSE_Peer_Review.pdf
Sunday, February 14, 2010
[Docket No. FSIS-2006-0011] FSIS Harvard Risk Assessment of Bovine Spongiform Encephalopathy (BSE)
http://bseusa.blogspot.com/2010/02/docket-no-fsis-2006-0011-fsis-harvard.html
----- Original Message -----
From: Terry S. Singeltary Sr.
To: Debra.Beasley@aphis.usda.gov
Sent: Tuesday, November 24, 2009 11:01 AM
Subject: OIE has recently published its proposed animal welfare guidelines for public comment
Greetings USDA/APHIS et al,
I would kindly like to comment on OIE proposed guidelines.
AS I said before, OIE should hang up there jock strap now, since it appears they will buckle every time a country makes some political hay about trade protocol, commodities and futures. IF they are not going to be science based, they should do everyone a favor and dissolve there organization. THE reason most every country around the globe came down with BSE/TSE in their cattle, were due to the failed and flawed BSE/TSE testing and surveillance policy of the O.I.E. NOW, they don't even acknowledge atypical scrapie it seems, as one for concern $
Monday, November 23, 2009
BSE GBR RISK ASSESSMENTS UPDATE NOVEMBER 23, 2009 COMMISSION OF THE EUROPEAN COMMUNITIES AND O.I.E.
http://docket-aphis-2006-0041.blogspot.com/2009/11/bse-gbr-risk-assessments-update.html
Tuesday, May 24, 2011 2:24 PM
O.I.E. Terrestrial Animal Health Standards Commission and prion (TSE) disease reporting 2011
http://transmissiblespongiformencephalopathy.blogspot.com/2011/05/oie-terrestrial-animal-health-standards.html
Saturday, June 19, 2010 U.S.
DENIED UPGRADED BSE STATUS FROM OIE
http://usdameatexport.blogspot.com/2010/06/us-denied-upgraded-bse-status-from-oie.html
IN A NUT SHELL ; $$$
(Adopted by the International Committee of the OIE on 23 May 2006)
11. Information published by the OIE is derived from appropriate declarations made by the official Veterinary Services of Member Countries.The OIE is not responsible for inaccurate publication of country disease status based on inaccurate information or changes in epidemiological status or other significant events that were not promptly reported to then Central Bureau............
http://www.oie.int/eng/Session2007/RF2006.pdf
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/pls/apex/f?p=2400:1001:5492868805159684::NO::F2400_P1001_BACK_PAGE,F2400_P1001_PUB_MAIL_ID:1000,86129
Scientific Report of the European Food Safety Authority on the Assessment of the Geographical BSE Risk (GBR) of the USA Question number: EFSA-Q-2003-083
Adopted: 1 July 2004
Summary
The European Food Safety Authority and its Scientific Expert Working Group on the Assessment of the Geographical Bovine Spongiform Encephalopathy (BSE) Risk (GBR) were asked by the European Commission (EC) to provide an up-to-date scientific report on the GBR in the United States of America, i.e. the likelihood of the presence of one or more cattle being infected with BSE, pre-clinically as well as clinically, in USA. This scientific report addresses the GBR of USA as assessed in 2004 based on data covering the period 1980-2003.
The BSE agent was probably imported into USA and could have reached domestic cattle in the middle of the eighties. These cattle imported in the mid eighties could have been rendered in the late eighties and therefore led to an internal challenge in the early nineties. It is possible that imported meat and bone meal (MBM) into the USA reached domestic cattle and leads to an internal challenge in the early nineties.
A processing risk developed in the late 80s/early 90s when cattle imports from BSE risk countries were slaughtered or died and were processed (partly) into feed, together with some imports of MBM. This risk continued to exist, and grew significantly in the mid 90’s when domestic cattle, infected by imported MBM, reached processing. Given the low stability of the system, the risk increased over the years with continued imports of cattle and MBM from BSE risk countries.
EFSA concludes that the current GBR level of USA is III, i.e. it is likely but not confirmed that domestic cattle are (clinically or pre-clinically) infected with the BSE-agent. As long as there are no significant changes in rendering or feeding, the stability remains extremely/very unstable. Thus, the probability of cattle to be (pre-clinically or clinically) infected with the BSE-agent persistently increases.
http://www.efsa.europa.eu/EFSA/efsa_locale-1178620753812_1211902594180.htm
Annex to the EFSA Scientific Report (2004) 3, 1-17 on the Assessment of the Geographical BSE Risk of USA - 1 - European Food Safety Authority Scientific Expert Working Group on GBR Working Group Report on the Assessment of the Geographical BSE-Risk (GBR) of UNITED STATES OF AMERICA 2004
Annex to the EFSA Scientific Report (2004) 3, 1-17 on the Assessment of the Geographical BSE Risk of USA - 7 - 2.3
Overall assessment of the external challenge
The level of the external challenge that has to be met by the BSE/cattle system is estimated according to the guidance given by the SSC in its final opinion on the GBR of July 2000 (as updated in January 2002). Live cattle imports: In total the country imported 2038 (other sources) or 1128 (CD) live cattle from BSE risk countries other than Canada, of which 327 (other sources) or 323 (CD) came from the UK. From Canada the imports were >500,000 animals per year. The numbers shown in table 1 are the raw import figures and are not reflecting the adjusted imports for the assessment of the external challenge. Broken down to 5 year periods the resulting external challenge is as given in table 3. This assessment takes into account the different aspects discussed above that allow to assume that certain imported cattle did not enter the domestic BSE-cattle system, i.e. were not rendered into feed. In the case of the USA, all the animals for which tracing information showed that they were not rendered were excluded from the external challenge.
MBM imports:
In total the country imported 689 tons MBM (CD) or 2,230 tons MBM (other sources) from BSE risk countries other than Canada, of which 5 tons (CD) or 101 tons (other sources) were exported from the UK (UK export data). From Canada, the imports were about 30 000 tons per year. The numbers shown in table 2 are the raw import figures and are not reflecting the adjusted imports for the assessment of the external challenge. Broken down to 5 year periods the resulting external challenge is as given in table 3. This assessment takes into account the different aspects discussed above that allow to assume that certain imported MBM did not enter the domestic BSE/cattle system or did not represent an external challenge for other reasons. As it was illegal to export mammalian MBM from UK since 27/03/1996, exports indicated after that date should only have included non-mammalian MBM. In the case of the USA imported MBM from UK in 1989 and between 1997 and 1999 was not taken into account.
Feeding Use of MBM in cattle feed • Until 1997 ruminant MBM (RMBM) could legally be included in cattle feed and was indeed commonly fed to cattle of different age and type. Prior to the feed ban the US authorities estimated that 10% of all MBM would deliberately have been fed to cattle. Feed bans • A ban to feed (several types of) MMBM to ruminants was put in place in August 1997. Derogation from the ban was granted for pure porcine and equine protein (MBM) coming from designated (single species) rendering plants. This MMBM might still be fed to cattle. Therefore this feed ban is a ruminant to ruminant ban. • It is planned to prohibit the use of all mammalian and poultry protein in ruminant feed and prohibiting materials from non-ambulatory disabled cattle and dead stock from use in all animal feed.
Conclusion on the ability to avoid recycling
• Before 1997, US system would not have been able to avoid recycling of the BSEagent to any measurable extent. If the BSE-agent was introduced into the feed chain, it could have reached cattle.
• After the introduction of the 1997 ban in August 1997, the ability to avoid recycling of BSE-infectivity was somewhat improved. However, the rendering of ruminant material (including SRM and fallen stock) is inadequate (non pressurized), and cross-contamination potentials of cattle feed with other feeds remain.
• Therefore, the system is still unable to avoid recycling of BSE-infectivity if already present in the system or incoming.
Feeding
Until August 1997, RMBM was legally fed to cattle. Feeding was therefore "not OK". In August 1997 an RMBM-ban was introduced but feeding of non-ruminant MBM to cattle remained legal as well as feeding of RMBM to non-ruminant animals (farm animals and pets). An RMBM ban is difficult to maintain, as only labels can distinguish the various MMBMs. This makes control of the feed ban very difficult because analytical differentiation between ruminant and non-ruminant MBM is difficult if not impossible.
Due to the highly specialised production system in the USA, various mammalian MBM streams can be separated. Such a feed ban would therefore be assessed as "reasonably OK", for all regions where this highly specialised system exists. However, several areas in the USA do have mixed farming and mixed feed mills, and in such regions an RMBM ban would not suffice. Additionally, official controls for cattle feeds to control for compliance with the ban started in 2002. Thus, for the whole country, the assessment of the feeding after 1997 remains "not OK", but improving.
Rendering
The rendering industry is operating with processes that are not known to reduce
infectivity. It is therefore concluded that rendering was and is "not OK".
SRM-removal
SRM were and are still rendered for feed, as are (parts of) the fallen stock. SRMremoval
is therefore regarded as "not OK".
BSE-surveillance
Before 1989, the ability of the system to identify (and eliminate) BSE-cases was
limited. Since 1990 this ability is improved, thanks to a specific (passive) BSE
surveillance. The initiated introduction of active surveillance in risk populations
should improve the system significantly.
On the basis of the available information, it has to be concluded that the country's
BSE/cattle system was extremely unstable until today, i.e., it would have recycled and
amplified BSE-infectivity very fast, should it have entered the system. The stability of
the BSE/cattle system in the USA overtime is as given in table 4.
The present assessment modifies the stability assessment of the previous GBR report
in 2000 mainly due to a different perception of the impact of BSE surveillance on
stability and of the efficiency of the RMBM feed ban.
Interaction of stability and external challenge in the USA
Period Stability External Challenge Internal challenge
1980 to
1985
1986 to
1990
Moderate Possibly present
1991 to 1995
Very high
1996 to
2000
2001 to
2003
Extremely unstable Extremely high Likely to be present and growing
5. CONCLUSION ON THE GEOGRAPHICAL BSE-RISK
5.1 The current GBR as function of the past stability and challenge
• The current geographical BSE risk (GBR) level is III, i.e. it is likely but not
confirmed that domestic cattle are (clinically or pre-clinically) infected with the
BSE-agent.
Note1: It is also worth noting that the current GBR conclusions are not dependent on
the large exchange of imports between USA and Canada. External challenge due to
exports to the USA from European countries varied from moderate to high. These
challenges indicate that it was likely that BSE infectivity was introduced into the
North American continent.
snip...please see full text ;
http://www.efsa.europa.eu/en/scdocs/doc/3rax1.pdf
HOWEVER, my files show 44 tons of greaves for USA. ...TSS
Subject: Re: exports from the U.K. of it's MBM to U.S.???
From: S.J.Pearsall@esg.maff.gsi.gov.uk
Date: Tue, 8 Feb 2000 14:03:16 +0000
To: flounder@wt.net (Receipt Notification Requested) (Non Receipt Notification Requested)
Terry Meat and bonemeal is not specifically classified for overseas trade purposes. The nearest equivalent is listed as flours and meals of meat or offals (including tankage), unfit for human consumption; greaves.
UK exports of this to the US are listed below:
Country Tonnes
1980
1981 12
1982
1983
1984 10
1985 2
1986
1987
1988
1989 20
1990
Data for exports between 1975 and 1979 are not readily available. These can be obtained (at a charge) from data retailers appointed by HM Customs and Excise: BTSL (Tel: 01372 463121) or Abacus (01245 252222).
Best wishes Simon Pearsall
Overseas trade statistics Stats (C&F)C
====================================== END...TSS
The most recent assessments (and reassessments) were published in June 2005 (Table I; 18), and included the categorisation of Canada, the USA, and Mexico as GBR III. Although only Canada and the USA have reported cases, the historically open system of trade in North America suggests that it is likely that BSE is present also in Mexico.
http://www.oie.int/boutique/extrait/06heim937950.pdf
PITUITARY EXTRACT
This was used to help cows super ovulate. This tissue was considered to be of greatest risk of containing BSE and consequently transmitting the disease...
http://collections.europarchive.org/tna/20090114081754/http://www.bseinquiry.gov.uk/files/yb/1988/06/08011001.pdf
NON-LICENSED HUMAN TISSUE DEVICES WERE NOT COMMERCIALLY AVAILABLE
snip...
I was quite prepared to believe in unofficial pituitary hormones, also in the 1970's, whether as described by Dr. Little, or in other circumstances, for animal use.
snip...
The fact that there were jars of pituitaries (or extract) around on shelves is attested by the still potent 1943 pituitaries, described in Stockell Hartree et al. (J/RF/17/291) which had come from the lab. at Mill Hill. Having taken the trouble to collect them, they were not lightly thrown out...
http://collections.europarchive.org/tna/20080102174454/http://www.bseinquiry.gov.uk/files/ws/s467bx.pdf
B.S.E. and Veterinary Medicines
Thank you very much indeed for your letter of the 26th of January outlining to me the various steps that are proposing to take in order to reduce the risk from B.S.E. in veterinary medicines. It is, as you say, and extremely difficult problem. ....
http://web.archive.org/web/20030526124448/http://www.bseinquiry.gov.uk/files/yb/1989/01/30008001.pdf
Draft cover letter to product licence holders (considered by Human and Vet Medicines including deer)
http://collections.europarchive.org/tna/20080103002832/http://www.bseinquiry.gov.uk/files/yb/1989/02/22008001.pdf
http://collections.europarchive.org/tna/20080102155758/http://www.bseinquiry.gov.uk/files/yb/1989/02/22011001.pdf
(It was noted with concern that hormone extracts could be manufactured by a veterinary surgeon for administration to animals under his care without any Medicines Act Control.)
PITUITARY EXTRACT
This was used to help cows super ovulate. This tissue was considered to be of greatest risk of containing BSE and consequently transmitting the disease.
BEEF BRAIN AND BRAIN INFUSION BROTHS
Considered to be of great risk.
http://collections.europarchive.org/tna/20080102164725/http://www.bseinquiry.gov.uk/files/yb/1988/06/08011001.pdf
COMMERCIAL IN CONFIDENCE
MEDICINES ACT - VETERINARY PRODUCTS COMMITTEE
5 BLANK PAGES. ...TSS
7. Any Other Business
http://collections.europarchive.org/tna/20080102164736/http://www.bseinquiry.gov.uk/files/yb/1988/06/07010001.pdf
TWA LITTLE STATEMENT 331
8 June 1988 Internal CVL meeting to discuss the implications of BSE to Biologicals Products containing bovine extracted material (Annex 6). (YB 88/06.08/11.1-11.2) Following a detailed review of situation the following recommendations were made:
1. Specific concern over use of pituitary gland products by veterinary surgeons and companies. Paper to be produced for Tolworth (Veterinary Medicines Division).
2. Urgent review of all products both immunological and pharmaceutical for possible inclusion of ingredients of bovine origin.
3. Draft guidelines to be presented in full to the National Office of Animal Health (NOAH), the trade body representing the Veterinary Medicines part of the pharmaceutical industry, at next meeting on 11 July 1988
http://collections.europarchive.org/tna/20080102163939/http://www.bseinquiry.gov.uk/files/ws/s331.pdf
TWA LITTLE minute
2. We have identified one problem over where we are unable to act and this is the use of gonadotrophins in embryo transfer work. Some veterinary surgeons are quite legally using this exemption from the Medicines Act contained in Section 9(2) to prepare gonadotrophins from pituitary glands from various species, including cattle. These hormones are used to stimulate superovulation in donor cows.
http://collections.europarchive.org/tna/20080102164806/http://www.bseinquiry.gov.uk/files/yb/1988/06/10001001.pdf
http://collections.europarchive.org/tna/20080102164811/http://www.bseinquiry.gov.uk/files/yb/1988/06/13010001.pdf
http://collections.europarchive.org/tna/20080103031215/http://www.bseinquiry.gov.uk/files/yb/1988/06/14006001.pdf
COMMERCIAL IN CONFIDENCE
3.2 Minute 5.3 - 5.4 Bovine Spongiform Encephalopathy
It was reported that some replies had been received from Companies using pituitary glands in their products. Copies of the BSE document had also been sent to DHSS and NIBSC.
and then another 3 + pages of blank space. ...TSS
http://collections.europarchive.org/tna/20080102164813/http://www.bseinquiry.gov.uk/files/yb/1988/09/06005001.pdf
COMMERCIAL IN CONFIDENCE
BSE - CURRENT POSITION WITH VETERINARY LICENCED PRODUCTS (MA.1968)
There are three areas of particular concern, vaccines (including emergency vaccines), pharmaceuticals which are covered by MA licences and unlicenses hormonal products produced under exemptions claimed under (Section 9(2) Medicines Act).
1) Vaccines
http://collections.europarchive.org/tna/20080103033809/http://www.bseinquiry.gov.uk/files/yb/1988/10/06005001.pdf
NOT FOR PUBLICATION
another 6 pages of blank space. ...TSS
http://collections.europarchive.org/tna/20080103032658/http://www.bseinquiry.gov.uk/files/yb/1988/11/01012001.pdf
http://collections.europarchive.org/tna/20080103032631/http://www.bseinquiry.gov.uk/files/yb/1988/11/04003001.pdf
http://collections.europarchive.org/tna/20080103033926/http://www.bseinquiry.gov.uk/files/yb/1988/04/00007001.pdf
COMMERCIAL IN CONFIDENCE
http://collections.europarchive.org/tna/20080103034137/http://www.bseinquiry.gov.uk/files/yb/1988/07/00007001.pdf
COMMERCIAL IN CONFIDENCE
Medicines Act - Veterinary Products Committee
http://collections.europarchive.org/tna/20080103034140/http://www.bseinquiry.gov.uk/files/yb/1988/09/00004001.pdf
COMMERCIAL IN CONFIDENCE
http://collections.europarchive.org/tna/20080102164744/http://www.bseinquiry.gov.uk/files/yb/1988/10/00003001.pdf
MANAGEMENT IN CONFIDENCE
CERTIFIED BSE-FREE HERDS FOR SOURCE OF MATERIAL FOR BIOLOGICAL PRODUCTS
http://collections.europarchive.org/tna/20080102184729/http://www.bseinquiry.gov.uk/files/yb/1989/01/04001001.pdf
Tuesday, February 8, 2011
U.S.A. 50 STATE BSE MAD COW CONFERENCE CALL Jan. 9, 2001
http://tseac.blogspot.com/2011/02/usa-50-state-bse-mad-cow-conference.html
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
Tuesday, November 02, 2010
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
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
Over the next 8-10 weeks, approximately 40% of all the adult mink on the farm died from TME.
snip...
The rancher was a ''dead stock'' feeder using mostly (>95%) downer or dead dairy cattle...
http://web.archive.org/web/20030516051623/http://www.bseinquiry.gov.uk/files/mb/m09/tab05.pdf
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
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
Thursday, July 21, 2011
A Second Case of Gerstmann-Sträussler-Scheinker Disease Linked to the G131V Mutation in the Prion Protein Gene in a Dutch Patient Journal of Neuropathology & Experimental Neurology:
August 2011 - Volume 70 - Issue 8 - pp 698-702
http://transmissiblespongiformencephalopathy.blogspot.com/2011/07/second-case-of-gerstmann-straussler.html
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
Wednesday, June 15, 2011
Galveston, Texas - Isle port moves through thousands of heifers headed to Russia, none from Texas, Alabama, or Washington, due to BSE risk factor
http://transmissiblespongiformencephalopathy.blogspot.com/2011/06/galveston-texas-isle-port-moves-through.html
Monday, May 30, 2011
CEPs for gelatin and impact of the revised EU Note for Guidance on the TSE risk EMEA/410/01 Rev.3) will come into force in July 2011
http://transmissiblespongiformencephalopathy.blogspot.com/2011/05/ceps-for-gelatin-and-impact-of-revised.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, August 12, 2011
Creutzfeldt-Jakob disease (CJD) biannual update (2011/2), Incidents Panel, National Anonymous Tonsil Archive
http://transmissiblespongiformencephalopathy.blogspot.com/2011/08/creutzfeldt-jakob-disease-cjd-biannual.html
Wednesday, June 29, 2011
TSEAC Meeting August 1, 2011 donor deferral Saudi Arabia vCJD risk blood and blood products
http://tseac.blogspot.com/2011/06/tseac-meeting-august-1-2011-donor.html
TSS
Saturday, August 13, 2011
Sensitive detection of prion proteins in blood
TSENEWS
Sensitive detection of prion proteins in blood
The incidence of BSE cases in cattle has declined, but the risk of contracting the human form of BSE, vCJD, remains a serious threat. In addition to eating contaminated beef, the disease can be also transmitted from one human being to another through organ and tissue transplantations and blood transfusions. The latter harbors an extreme potential risk, since blood from one donor can infect multiple receivers. Recent research has demonstrated that sensitive detection of prions in blood is possible. Using a combination of Prionics antibody 15B3 and prion amplification, the blood test is 10,000 times more sensitive than previously reported assays.
Prion diseases are caused by aberrantly folded prion proteins that accumulate in the brain, resulting in serious brain damage. Several scientific groups have reported long incubation times for vCJD before clinical symptoms appear. Therefore, an individual incubating vCJD can donate blood and spread the disease to multiple receivers. As low levels of prions are expected to be present in the blood of vCJD patients, sensitive detection of disease-specific prion proteins is of great importance for the safety of human blood donations. A recent publication by the group of Byron Caughey describes a new and very sensitive method for the detection of disease-specific prion proteins in blood or plasma. This eQuIC assay uses amplification of prions together with a concentration step using the Prionics 15B3 antibody.
10,000 fold more sensitive The monoclonal 15B3 antibody (mAb 15B3), developed by Prionics, has been shown to specifically recognize the disease-specific form of the prion protein (PrPSc). In the publication of Caughey and his group, the mAb 15B3 was used to “fish” PrPSc from a blood sample. This concentration step alone, however, did not suffice for the detection of prions in the blood. The researchers therefore used the quaking-induced conversion method to amplify disease-specific prions in the concentrated sample. This combination of concentration and amplification, which the researchers call eQuIC, resulted in a 10,000 fold more sensitive assay than those previously reported. Dilutions of 1014-fold, containing ~2 attogram per milliliter of proteinase K-resistant prion protein, were readily detected.
About the is eQuIC method The method used for prion amplification is the quaking-induced conversion (QuIC) reaction. The method is a cell-free conversion reaction of PrPC to PrPSc in multiwell plates. PrPSc present in the (blood) sample acts as a seed for the conversion of recombinant PrP added to the reaction as a substrate. PrPSc complexes formed in the tube are then disrupted by shaking, providing further scaffolds for prion protein conversion. In the real-time quaking-induced conversion, detection of formed PrPSc is based on thioflavin T fluorescence which is enhanced when bound to prion amyloids. Caughey and colleagues combined the real-time quaking-induced conversion with prior immunoprecipitation using mAb 15B3 and called the method enhanced real-time Quaking-Induced Conversion (eQuIC).
http://escope.prionics.com/issue/2011-august-2/
Prion Disease Blood Test Using Immunoprecipitation and Improved Quaking-Induced Conversion
Christina D. Orrú,a Jason M. Wilham,a Lynne D. Raymond,a Franziska Kuhn,b Björn Schroeder,b Alex J. Raeber,b and Byron Caugheya Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA,a and Prionics AG, Zurich, Switzerlandb
ABSTRACT
A key challenge in managing transmissible spongiform encephalopathies (TSEs) or prion diseases in medicine, agriculture, and wildlife biology is the development of practical tests for prions that are at or below infectious levels. Of particular interest are tests capable of detecting prions in blood components such as plasma, but blood typically has extremely low prion concentrations and contains inhibitors of the most sensitive prion tests. One of the latter tests is quaking-induced conversion (QuIC), which can be as sensitive as in vivo bioassays, but much more rapid, higher throughput, and less expensive. Now we have integrated antibody 15B3-based immunoprecipitation with QuIC reactions to increase sensitivity and isolate prions from inhibitors such as those in plasma samples. Coupling of immunoprecipitation and an improved real-time QuIC reaction dramatically enhanced detection of variant Creutzfeldt-Jakob disease (vCJD) brain tissue diluted into human plasma. Dilutions of 1014-fold, containing ~2 attogram (ag) per ml of proteinase K-resistant prion protein, were readily detected, indicating ~10,000- fold greater sensitivity for vCJD brain than has previously been reported. We also discriminated between plasma and serum samples from scrapie-infected and uninfected hamsters, even in early preclinical stages. This combined assay, which we call “enhanced QuIC” (eQuIC), markedly improves prospects for routine detection of low levels of prions in tissues, fluids, or environmental samples.
IMPORTANCE
Transmissible spongiform encephalopathies (TSEs) are largely untreatable and are difficult to diagnose definitively prior to irreversible clinical decline or death. The transmissibility of TSEs within and between species highlights the need for practical tests for even the smallest amounts of infectivity. A few sufficiently sensitive in vitro methods have been reported, but most have major limitations that would preclude their use in routine diagnostic or screening applications. Our new assay improves the outlook for such critical applications. We focused initially on blood plasma because a practical blood test for prions would be especially valuable for TSE diagnostics and risk reduction. Variant Creutzfeldt-Jakob disease (vCJD) in particular has been transmitted between humans via blood transfusions. Enhanced real-time quaking-induced conversion (eQuIC) provides by far the most sensitive detection of vCJD to date. The 15B3 antibody binds prions of multiple species, suggesting that our assay may be useful for clinical and fundamental studies of a variety of TSEs of humans and animals. Received 8 April 2011 Accepted 12 April 2011 Published 10 May 2011 Citation Orrú CD, et al. 2011. Prion disease blood test using immunoprecipitation and improved quaking-induced conversion. mBio 2(3):e00078-11. doi:10.1128/mBio.00078- 11. Editor Reed Wickner, National Institutes of Health Copyright © 2011 Orrú et al. This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported License, which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original author and source are credited. Address correspondence to Byron Caughey, bcaughey@nih.gov.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3101782/pdf/mBio.00078-11.pdf
Friday, July 29, 2011
Real-time quaking-induced conversion A highly sensitive assay for prion detection
http://transmissiblespongiformencephalopathy.blogspot.com/2011/07/real-time-quaking-induced-conversion.html
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/pls/apex/f?p=2400:1001:5492868805159684::NO::F2400_P1001_BACK_PAGE,F2400_P1001_PUB_MAIL_ID:1000,86129
Thursday, July 28, 2011
An Update on the Animal Disease Traceability Framework July 27, 2011
http://naiscoolyes.blogspot.com/2011/07/update-on-animal-disease-traceability.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
Over the next 8-10 weeks, approximately 40% of all the adult mink on the farm died from TME.
snip...
The rancher was a ''dead stock'' feeder using mostly (>95%) downer or dead dairy cattle...
http://web.archive.org/web/20030516051623/http://www.bseinquiry.gov.uk/files/mb/m09/tab05.pdf
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
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
Thursday, July 21, 2011
A Second Case of Gerstmann-Sträussler-Scheinker Disease Linked to the G131V Mutation in the Prion Protein Gene in a Dutch Patient Journal of Neuropathology & Experimental Neurology:
August 2011 - Volume 70 - Issue 8 - pp 698-702
http://transmissiblespongiformencephalopathy.blogspot.com/2011/07/second-case-of-gerstmann-straussler.html
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
Wednesday, June 15, 2011
Galveston, Texas - Isle port moves through thousands of heifers headed to Russia, none from Texas, Alabama, or Washington, due to BSE risk factor
http://transmissiblespongiformencephalopathy.blogspot.com/2011/06/galveston-texas-isle-port-moves-through.html
Thursday, July 28, 2011
An Update on the Animal Disease Traceability Framework July 27, 2011
http://naiscoolyes.blogspot.com/2011/07/update-on-animal-disease-traceability.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
Thursday, May 26, 2011
Travel History, Hunting, and Venison Consumption Related to Prion Disease Exposure, 2006-2007 FoodNet Population Survey
Journal of the American Dietetic Association Volume 111, Issue 6 , Pages 858-863, June 2011.
http://transmissiblespongiformencephalopathy.blogspot.com/2011/05/travel-history-hunting-and-venison.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 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
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
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
Tuesday, April 26, 2011
sporadic CJD RISING Text and figures of the latest annual report of the NCJDRSU covering the period 1990-2009 (published 11th March 2011)
http://creutzfeldt-jakob-disease.blogspot.com/2011/04/sporadic-cjd-rising-text-and-figures-of.html
Thursday, August 4, 2011
Terry Singeltary Sr. on the Creutzfeldt-Jakob Disease Public Health Crisis, Date aired: 27 Jun 2011
http://transmissiblespongiformencephalopathy.blogspot.com/2011/08/terry-singeltary-sr-on-creutzfeldt.html
Friday, August 12, 2011
Creutzfeldt-Jakob disease (CJD) biannual update (2011/2), Incidents Panel, National Anonymous Tonsil Archive
http://transmissiblespongiformencephalopathy.blogspot.com/2011/08/creutzfeldt-jakob-disease-cjd-biannual.html
TSS
Sensitive detection of prion proteins in blood
The incidence of BSE cases in cattle has declined, but the risk of contracting the human form of BSE, vCJD, remains a serious threat. In addition to eating contaminated beef, the disease can be also transmitted from one human being to another through organ and tissue transplantations and blood transfusions. The latter harbors an extreme potential risk, since blood from one donor can infect multiple receivers. Recent research has demonstrated that sensitive detection of prions in blood is possible. Using a combination of Prionics antibody 15B3 and prion amplification, the blood test is 10,000 times more sensitive than previously reported assays.
Prion diseases are caused by aberrantly folded prion proteins that accumulate in the brain, resulting in serious brain damage. Several scientific groups have reported long incubation times for vCJD before clinical symptoms appear. Therefore, an individual incubating vCJD can donate blood and spread the disease to multiple receivers. As low levels of prions are expected to be present in the blood of vCJD patients, sensitive detection of disease-specific prion proteins is of great importance for the safety of human blood donations. A recent publication by the group of Byron Caughey describes a new and very sensitive method for the detection of disease-specific prion proteins in blood or plasma. This eQuIC assay uses amplification of prions together with a concentration step using the Prionics 15B3 antibody.
10,000 fold more sensitive The monoclonal 15B3 antibody (mAb 15B3), developed by Prionics, has been shown to specifically recognize the disease-specific form of the prion protein (PrPSc). In the publication of Caughey and his group, the mAb 15B3 was used to “fish” PrPSc from a blood sample. This concentration step alone, however, did not suffice for the detection of prions in the blood. The researchers therefore used the quaking-induced conversion method to amplify disease-specific prions in the concentrated sample. This combination of concentration and amplification, which the researchers call eQuIC, resulted in a 10,000 fold more sensitive assay than those previously reported. Dilutions of 1014-fold, containing ~2 attogram per milliliter of proteinase K-resistant prion protein, were readily detected.
About the is eQuIC method The method used for prion amplification is the quaking-induced conversion (QuIC) reaction. The method is a cell-free conversion reaction of PrPC to PrPSc in multiwell plates. PrPSc present in the (blood) sample acts as a seed for the conversion of recombinant PrP added to the reaction as a substrate. PrPSc complexes formed in the tube are then disrupted by shaking, providing further scaffolds for prion protein conversion. In the real-time quaking-induced conversion, detection of formed PrPSc is based on thioflavin T fluorescence which is enhanced when bound to prion amyloids. Caughey and colleagues combined the real-time quaking-induced conversion with prior immunoprecipitation using mAb 15B3 and called the method enhanced real-time Quaking-Induced Conversion (eQuIC).
http://escope.prionics.com/issue/2011-august-2/
Prion Disease Blood Test Using Immunoprecipitation and Improved Quaking-Induced Conversion
Christina D. Orrú,a Jason M. Wilham,a Lynne D. Raymond,a Franziska Kuhn,b Björn Schroeder,b Alex J. Raeber,b and Byron Caugheya Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA,a and Prionics AG, Zurich, Switzerlandb
ABSTRACT
A key challenge in managing transmissible spongiform encephalopathies (TSEs) or prion diseases in medicine, agriculture, and wildlife biology is the development of practical tests for prions that are at or below infectious levels. Of particular interest are tests capable of detecting prions in blood components such as plasma, but blood typically has extremely low prion concentrations and contains inhibitors of the most sensitive prion tests. One of the latter tests is quaking-induced conversion (QuIC), which can be as sensitive as in vivo bioassays, but much more rapid, higher throughput, and less expensive. Now we have integrated antibody 15B3-based immunoprecipitation with QuIC reactions to increase sensitivity and isolate prions from inhibitors such as those in plasma samples. Coupling of immunoprecipitation and an improved real-time QuIC reaction dramatically enhanced detection of variant Creutzfeldt-Jakob disease (vCJD) brain tissue diluted into human plasma. Dilutions of 1014-fold, containing ~2 attogram (ag) per ml of proteinase K-resistant prion protein, were readily detected, indicating ~10,000- fold greater sensitivity for vCJD brain than has previously been reported. We also discriminated between plasma and serum samples from scrapie-infected and uninfected hamsters, even in early preclinical stages. This combined assay, which we call “enhanced QuIC” (eQuIC), markedly improves prospects for routine detection of low levels of prions in tissues, fluids, or environmental samples.
IMPORTANCE
Transmissible spongiform encephalopathies (TSEs) are largely untreatable and are difficult to diagnose definitively prior to irreversible clinical decline or death. The transmissibility of TSEs within and between species highlights the need for practical tests for even the smallest amounts of infectivity. A few sufficiently sensitive in vitro methods have been reported, but most have major limitations that would preclude their use in routine diagnostic or screening applications. Our new assay improves the outlook for such critical applications. We focused initially on blood plasma because a practical blood test for prions would be especially valuable for TSE diagnostics and risk reduction. Variant Creutzfeldt-Jakob disease (vCJD) in particular has been transmitted between humans via blood transfusions. Enhanced real-time quaking-induced conversion (eQuIC) provides by far the most sensitive detection of vCJD to date. The 15B3 antibody binds prions of multiple species, suggesting that our assay may be useful for clinical and fundamental studies of a variety of TSEs of humans and animals. Received 8 April 2011 Accepted 12 April 2011 Published 10 May 2011 Citation Orrú CD, et al. 2011. Prion disease blood test using immunoprecipitation and improved quaking-induced conversion. mBio 2(3):e00078-11. doi:10.1128/mBio.00078- 11. Editor Reed Wickner, National Institutes of Health Copyright © 2011 Orrú et al. This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported License, which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original author and source are credited. Address correspondence to Byron Caughey, bcaughey@nih.gov.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3101782/pdf/mBio.00078-11.pdf
Friday, July 29, 2011
Real-time quaking-induced conversion A highly sensitive assay for prion detection
http://transmissiblespongiformencephalopathy.blogspot.com/2011/07/real-time-quaking-induced-conversion.html
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/pls/apex/f?p=2400:1001:5492868805159684::NO::F2400_P1001_BACK_PAGE,F2400_P1001_PUB_MAIL_ID:1000,86129
Thursday, July 28, 2011
An Update on the Animal Disease Traceability Framework July 27, 2011
http://naiscoolyes.blogspot.com/2011/07/update-on-animal-disease-traceability.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
Over the next 8-10 weeks, approximately 40% of all the adult mink on the farm died from TME.
snip...
The rancher was a ''dead stock'' feeder using mostly (>95%) downer or dead dairy cattle...
http://web.archive.org/web/20030516051623/http://www.bseinquiry.gov.uk/files/mb/m09/tab05.pdf
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
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
Thursday, July 21, 2011
A Second Case of Gerstmann-Sträussler-Scheinker Disease Linked to the G131V Mutation in the Prion Protein Gene in a Dutch Patient Journal of Neuropathology & Experimental Neurology:
August 2011 - Volume 70 - Issue 8 - pp 698-702
http://transmissiblespongiformencephalopathy.blogspot.com/2011/07/second-case-of-gerstmann-straussler.html
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
Wednesday, June 15, 2011
Galveston, Texas - Isle port moves through thousands of heifers headed to Russia, none from Texas, Alabama, or Washington, due to BSE risk factor
http://transmissiblespongiformencephalopathy.blogspot.com/2011/06/galveston-texas-isle-port-moves-through.html
Thursday, July 28, 2011
An Update on the Animal Disease Traceability Framework July 27, 2011
http://naiscoolyes.blogspot.com/2011/07/update-on-animal-disease-traceability.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
Thursday, May 26, 2011
Travel History, Hunting, and Venison Consumption Related to Prion Disease Exposure, 2006-2007 FoodNet Population Survey
Journal of the American Dietetic Association Volume 111, Issue 6 , Pages 858-863, June 2011.
http://transmissiblespongiformencephalopathy.blogspot.com/2011/05/travel-history-hunting-and-venison.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 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
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
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
Tuesday, April 26, 2011
sporadic CJD RISING Text and figures of the latest annual report of the NCJDRSU covering the period 1990-2009 (published 11th March 2011)
http://creutzfeldt-jakob-disease.blogspot.com/2011/04/sporadic-cjd-rising-text-and-figures-of.html
Thursday, August 4, 2011
Terry Singeltary Sr. on the Creutzfeldt-Jakob Disease Public Health Crisis, Date aired: 27 Jun 2011
http://transmissiblespongiformencephalopathy.blogspot.com/2011/08/terry-singeltary-sr-on-creutzfeldt.html
Friday, August 12, 2011
Creutzfeldt-Jakob disease (CJD) biannual update (2011/2), Incidents Panel, National Anonymous Tonsil Archive
http://transmissiblespongiformencephalopathy.blogspot.com/2011/08/creutzfeldt-jakob-disease-cjd-biannual.html
TSS
Friday, August 12, 2011
Creutzfeldt-Jakob disease (CJD) biannual update (2011/2), Incidents Panel, National Anonymous Tonsil Archive
Creutzfeldt-Jakob disease (CJD) biannual update (2011/2) This six-monthly report provides an update on reports of incidents of potential iatrogenic (healthcare-acquired) exposure to CJD, and on the National Anonymous Tonsil Archive. The data are correct as of 12 July 2011.
For numbers of CJD case reports, readers should consult data provided by the National CJD Research and Surveillance Unit (NCJDRSU), Edinburgh [1]. The latest yearly analysis of vCJD reports (onsets and deaths) is also available from the NCJDRSU website [2].
Reports of incidents of potential iatrogenic exposure to CJD via surgery: 2000 to 30 June 2011.
A surgical incident occurs when a patient with or at increased risk of CJD has undergone surgery without the appropriate infection control guidance being followed [3]. This could happen if a patient undergoes surgery during the incubation period of CJD, or because information about CJD risk factors is not available at the time of surgery. If this happens, surgical instruments that may be contaminated with the infectious agent that causes CJD, could pose a transmission risk when they are re-used on other patients.
In June 2010 the CJD Incidents Panel changed its protocol for reporting surgical incidents, and a new reporting algorithm was published on the HPA CJD Section website. Under the new protocol only CJD cases (or patients at increased risk of CJD) who have undergone surgical procedures which are thought to pose a possible transmission risk (i.e. within the likely infectious incubation period, and involving medium or high risk procedures) are categorised as ‘surgical incidents'. Other procedures, either earlier in the incubation period, or involving low infectivity tissues, are categorised as ‘CJD Reports'.
Advice has been issued for one surgical incident and twelve CJD reports that have been reported to the CJD Incidents Panel in the first six months of 2011. Table 1 shows the number of CJD surgical incidents reported to the CJD Incidents Panel from 2000 to 30 June 2011 by the diagnosis of the index patient. As shown in the table, 45% of surgical incidents result from surgery on index cases diagnosed with sporadic CJD.
Information about the CJD Incidents Panel can be found on the HPA website [4].
Table 1: CJD surgical incidents (n=437) reported to the CJD Incidents Panel (which have been closed, or where advice has been issued) by diagnosis of index patient: 2000 to 30th June 2011 Index patient status '00 '01 '02 '03 '04 '05 '06 '07 '08 '09 '10 '11 Total incidents (% of total) Total CJD reports
Incid'ts Rep'ts Incid'ts Rep'ts Sporadic (possible, probable or definite) 7 19 22 24 16 18 31 17 21 15 5 4 1 12 196 (45%) 16
vCJD (possible, probable or definite) 6 14 22 5 4 1 2 – 1 – 56 (13%) –
Familial including 'at risk' familial – 2 7 1 3 7 – 2 3 2 – 29 (7%) –
'At risk' vCJD blood component recipient – 4 10 5 1 – 2 – 22 (5%) –
'At risk' - vCJD plasma product recipient – 1 2 – 10 18 9 8 6 9 3 – 66 (15%) –
'At risk' - other – 2 1 2 5 – 1 7 – 20 (5%) –
CJD type unclear/ CJD unlikely 1 – 4 1 2 – 10 (2%) –
Not CJD 2 1 4 7 1 – 3 – 1 – 27 (6%) –
Other – 1 2 1 – 1 – 7 (2%) –
No longer considered 'at-risk' – 1 – 1 – 2 – 4 (1%) –
Total 16 38 56 50 45 56 63 27 33 29 23 4 1 12 437 100% 16
Note: The totals in 2009 and 2010 have changed from those reported in February 2011 as incidents have been closed, or advice has been issued, since the database was archived for the February 2011 report.
If the investigation of a surgical incident identifies any instruments that are considered to be potentially contaminated with the infectious agent, and that could still pose an infection risk to other patients, the Panel advises that these instruments should be removed from general use or refurbished. These instruments may be quarantined, kept for exclusive use on the index patient, refurbished (endoscopes only) or destroyed.
Since 2000 there have been 84 incidents in which instruments have been permanently removed from general use or refurbished (endoscopes only). This is a reduction in the total given in the February 2011 report, as in 2011 the CJD Incidents Panel revised its advice on the re-use of endoscopes that had been through over ten cycles of re-use and decontamination, so that these endoscopes could be returned to general use. This resulted in the Panel revising its advice on endoscopes used in six incidents that were reported in 2010, so that in five of these incidents the Panel advised that none of the instruments involved needed to be removed from general use.
Surgical incidents resulting in ‘at risk’ patients
The Panel may advise contacting and informing patients of their possible exposure to CJD following a surgical incident. These patients should be considered 'at-risk of CJD for public health purposes' and are asked to take certain precautions (i.e. not to donate blood, other tissues or organs, and to inform their medical and dental carers prior to any invasive procedures) in order to reduce the risk of transmitting the CJD agent.
The diagnosis of the index patient; the timing of the procedure relative to the development of clinical CJD; the tissue that instruments were in contact with during the procedure on the index patient; and the number of cycles of re-use and decontamination the instruments have been through following the procedure on the index case – all influence the possible risk to subsequent patients.
The threshold level of risk at which patients are considered to be ‘at increased risk’ of CJD is 1%, in addition to the background risk in the UK population. This risk threshold is based on risk assessment models, using precautionary assumptions. The 1% threshold level is used as a cut off for implementing public health precautions and is not intended to be a precise measure of an individual patient's risk. A similar threshold is used for identifying other patients who have been exposed to possible CJD risks following surgical, blood, plasma and tissue incidents.
From 2000 to 30 June 2011, there have been 25 surgical incidents in which the Panel has advised that 179 patients should be considered to have an increased risk of CJD.
Patient denotifications
Following changes in the assessment of tissue infectivity, the Panel has advised that 38 patients in 14 surgical incidents who were originally considered (and notified) as being ‘at risk' of CJD should no longer be considered ‘at risk', and should be denotified. In November 2005, gastrointestinal endoscopies without invasive procedures were reclassified as low risk procedures, and advice was issued to denotify two patients in one surgical incident. In 2006, anterior eye was reclassified as a ‘medium low' infectivity tissue. This led to a change in advice as only the first patient on whom instruments were used following an anterior eye procedure was to be considered as having an increased risk of CJD. Previously this had applied to the first two patients exposed to such instruments. This resulted in the Panel advising that 16 patients in seven incidents should be denotified. In 2009, the anterior eye was further reclassified as a low infectivity tissue. Following this change, the Panel advised that 20 patients should be denotified.
As of 30 June 2011, the Panel has received confirmation that of the 34 patients originally notified of their exposure (out of the 38 originally considered to be ‘at risk'), 26 patients have been informed that they are no longer considered ‘at risk' and eight patients died before they could be denotified.
Current 'at risk' patients resulting from surgical instruments
There are 12 surgical incidents in which 141 patients are still considered to be at increased risk of CJD. Currently, 119 of these 'at risk' patients have been notified that they are at increased risk of CJD. Local decisions have been taken not to notify four patients in these incidents.
Table 2: Surgical ‘at risk’ patients still identified as being ‘at increased risk of CJD’ by the Panel by procedure on the index patient Diagnosis of index patient Procedure on index patient Number of incidents Patients identified as 'at risk' Patients who died before being notified Local decision not to notify patient Notified patients
Sporadic Brain biopsy 2 28 2 1 25
Variant Appendectomy 1 2 – 2 –
Variant Endoscopy 1 – 1 –
Asymptomatic infected vCJD Endoscopy 1 4 1 – 3
At risk variant Endoscopy 5 36 4 – 32
At risk familial Neurosurgery 1 31 10 – 21
At risk familial Ophthalmic surgery 1 39 1 – 38
Total
12 141 18 4 119
Monitoring of patients 'at increased risk' of CJD
The CJD Incidents Panel and the Advisory Committee on Dangerous Pathogens Transmissible Spongiform Encephalopathy Risk Management Subgroup (formerly the ACDP TSE Working Group) have identified a range of individuals and groups who may have been exposed to an increased risk of CJD as a consequence of their medical care (see table 3 below). The risks of iatrogenic CJD transmission to these different individuals are very uncertain, but potentially devastating. The CJD Incidents Panel has advised that these individuals should be informed of their risk and asked to follow public health precautions to avoid transmitting the infection to others.
It is important to follow up these individuals to help determine the risks of CJD spreading to patients through different routes. Follow up involves a range of activities and is carried out by different organisations. At core, follow up aims to ascertain whether any people who may have been exposed to increased CJD risks go on to develop CJD.
Table 3. Individuals at increased risk of CJD up to 30 June 2011 'At risk' Group Identified as 'at risk' Ever notified as being 'at risk' Alive and Notified Cases Asymptomatic infections
Recipients of blood from vCJD cases 66 27 18 3 1
Blood donors to vCJD cases 112 107 105 –
Other recipients from blood donors to vCJD cases 34 32 30 –
Plasma product recipients (all except one have non-bleeding disorders) 11 10 3 [c] –
Surgical contacts of all CJD cases 141 119 111 –
Highly transfused patients (recipients of blood from =80 donors identified at pre-surgical assessment) 7 6 5 –
Total for at risk groups where HPA holds data 371 301 273 3 1
Patients with bleeding disorders who received UK sourced plasma products [a] 3,840 n/k – 1
Recipients of human derived growth hormone [b] 1,883 Up to 1,883 Up to 1,527 64 –
Total for all 'at risk' groups [d] 6094 At least 2184 At least 1800 67 2
a. Data provided by the UK Haemophilia Centre Doctors' Organisation (UKHCDO). These are minimum figures. Central reporting for bleeding disorder patients is incomplete, and some patients have opted out of the central UKHCDO database. Individual haemophilia centres were asked to send out standardised letters of notification to all their ‘at risk’ patients, but the exact number of patients who received these letters and are therefore aware of their risk is not known. b. Data provided by the Institute for Child Health. A small number of ‘at risk' growth hormone recipients are not included in the Institute of Child Health study so the true number ‘at risk’ will be greater. The exact number of growth hormone recipients in the ICH study currently aware of their risk is not known, as given their age at the original notification many were informed indirectly, by their parents. c. The current status for one plasma ‘at risk' patient is under review by Health Protection Scotland. d. These are minimum figures given the comments made above.
Six-monthly update on the National Anonymous Tonsil Archive: end of July 2011
The National Anonymous Tonsil Archive (NATA) was set up in 2004 to prospectively collect 100,000 tonsils pairs obtained after routine tonsillectomies in England and Scotland and to test these samples for abnormal prion protein. Only tissue not required for patient care, which would normally be discarded, is collected. Tonsils are tested for abnormal prion protein by two commercial enzyme immunoassays (EIAs), and a small proportion selected for other analytical tests. Initial results from analysis of 63,007 of the tonsil samples, indicated that all tonsils were negative so far for the detection of PrPCJD protein [5].
Up to the end of July 2011, NATA has received a total of 94,611 tonsil pairs from hospitals in England and Scotland, about 17,849 of which are from the birth cohort in which most vCJD cases have arisen (1961-1985). A further 3,000 tonsil pairs have been received from the Medical Research Council Prion Unit at the UCL Institute for Neurology, National Hospital for Neurology and Neurosurgery. Therefore the total number of tonsil pairs in the archive as at the end of July 2011 was 96,949. The number of collection forms that were completed but where no tonsil tissue was collected was 2,541 (1,663 due to patient objection and 878 due to clinical pathology being requested).
Of the 100 NHS Hospital Trusts that perform over 200 tonsillectomies per year in England, 91 have been recruited and are currently sending tonsil pairs to NATA on a regular basis. There are 120 hospital sites within these trusts taking part in NATA. At present, approximately 50,000 tonsillectomies are performed annually in England. Figure 4 shows the number of tonsil pairs received from each Strategic Health Authority area.
Figure 1. Number of tonsil pairs collected for NATA quarterly (Q1, 2004 to Q3, 2011)
Figure 2. Tonsils pairs collected by Strategic Health Authority (January 2004 to July 2011)
Figure 3. NHS Trusts and Scottish hospitals currently collecting and sending tonsil tissue to the archive July 2011
References
1. The National Creutzfeldt-Jakob Disease Research and Surveillance Unit, The University of Edinburgh. CJD statistics. Available at: http://www.cjd.ed.ac.uk/figures.htm.
2. The National Creutzfeldt-Jakob Disease Research and Surveillance Unit, The University of Edinburgh. Incidence of variant Creutzfeldt-Jakob disease onsets and deaths in the UK January 1994 - May 2011. Edinburgh: NCJDSU, 18 May 2011. Available at: http://www.cjd.ed.ac.uk/cjdq68.pdf.
3. Transmissible spongiform encephalopathy agents: safe working and the prevention of infection. The ACDP TSE Risk Management Subgroup. http://www.dh.gov.uk/ab/ACDP/TSEguidance/index.htm.
4. HPA CJD Incidents Panel [online]. Available at: http://www.hpa.org.uk/web/ CJDIncidentsPanel.
5. Clewley J, Kelly CM, Andrews N, Vogliqi K, Mallinson G, Kaisar M, et al. Prevalence of disease related prion protein in anonymous tonsil specimens in Britain: cross sectional opportunistic survey. BMJ 2009; 338: b1442.
http://www.hpa.org.uk/hpr/infections/ei_cjd.htm
2008
POSITION STATEMENT PREVALENCE OF SUBCLINICAL VARIANT CREUTZFELDT-JAKOB DISEASE INFECTIONS
http://webarchive.nationalarchives.gov.uk/20110316162913/http://www.seac.gov.uk/statements/state-cjd-infections.pdf
2009
BMJ 2009; 338:b1442 doi: 10.1136/bmj.b1442 (Published 21 May 2009) Cite this as: BMJ 2009; 338:b1442 Research
Prevalence of disease related prion protein in anonymous tonsil specimens in Britain: cross sectional opportunistic survey
Jonathan P Clewley, clinical scientist1, Carole M Kelly, research epidemiologist1, Nick Andrews, statistician1, Kelly Vogliqi, research technician1, Gary Mallinson, clinical scientist2, Maria Kaisar, research scientist2, David A Hilton, consultant neuropathologist3, James W Ironside, professor of clinical neuropathology4, Philip Edwards, biomedical scientist3, Linda M McCardle, biomedical scientist4, Diane L Ritchie, research assistant4, Reza Dabaghian, research scientist1, Helen E Ambrose, research scientist1, O Noel Gill, consultant epidemiologist1
+ Author Affiliations
1Centre for Infections, Health Protection Agency, London NW9 5EQ
2Bristol Institute for Transfusion Sciences, National Blood Service, Bristol BS10 5ND
3Department of Histopathology, Derriford Hospital, Plymouth PL6 8DH
4National CJD Surveillance Unit, University of Edinburgh, Western General Hospital, Edinburgh EH4 2XU
Correspondence to: JP Clewley jonathan.clewley@hpa.org.uk Accepted 15 December 2008
Abstract
Objective
To establish with improved accuracy the prevalence of disease related prion protein (PrPCJD) in the population of Britain and thereby guide a proportionate public health response to limit the threat of healthcare associated transmission of variant Creutzfeldt-Jakob disease (vCJD).
Design Cross sectional opportunistic survey.
Study samples Anonymised tonsil pairs removed at elective tonsillectomy throughout England and Scotland.
Setting National anonymous tissue archive for England and Scotland.
Main outcome measure Presence of PrPCJD determined by using two enzyme immunoassays based on different analytical principles, with further investigation by immunohistochemistry or immunoblotting of any samples reactive in either assay.
Results Testing of 63007 samples was completed by the end of September 2008. Of these, 12753 were from the birth cohort in which most vCJD cases have arisen (1961-85) and 19908 were from the 1986-95 cohort that would have been also exposed to bovine spongiform encephalopathy through infected meat or meat products. None of the samples tested was unequivocally reactive in both enzyme immunoassays.
Only two samples were reactive in one or other enzyme immunoassay and equivocal in the other, and nine samples were equivocally reactive in both enzyme immunoassays.
Two hundred and seventy six samples were initially reactive in one or other enzyme immunoassay; the repeat reactivity rate was 15% or less, depending on the enzyme immunoassay and cut-off definition. None of the samples (including all the 276 initially reactive in enzyme immunoassay) that were investigated by immunohistochemistry or immunoblotting was positive for the presence of PrPCJD.
Conclusions The observed prevalence of PrPCJD in tonsils from the 1961-95 combined birth cohort was 0/32661 with a 95% confidence interval of 0 to 113 per million. In the 1961-85 cohort, the prevalence of zero with a 95% confidence interval of 0 to 289 per million was lower than, but still consistent with, a previous survey of appendix tissue that showed a prevalence of 292 per million with a 95% confidence interval of 60 to 853 per million. Continuing to archive and test tonsil specimens, especially in older birth cohorts, and other complementary large scale anonymous tissue surveys, particularly of post-mortem tissues, will further refine the calculated prevalence of PrPCJD.
http://www.bmj.com/content/338/bmj.b1442.full.pdf
2010
Large-scale immunohistochemical examination for lymphoreticular prion protein in tonsil specimens collected in Britain†
Mar Fernandez de Marco1, Jacqueline Linehan2, O Noel Gill3, Jonathan P Clewley3,*, Sebastian Brandner1,*Article first published online: 4 OCT 2010
DOI: 10.1002/path.2767
Keywords:variant Creutzfeldt–Jakob disease;bovine spongiform encephalopathy;vCJD prevalence;PrP
Abstract
There have been 173 cases of variant Creutzfeldt–Jakob disease (vCJD) in the UK, as of 5 July 2010, as a result of the bovine spongiform encephalopathy epidemic. The number of individuals subclinically infected with vCJD, and thus the eventual number of cases, remains, however, uncertain. In an attempt to address this problem, 63 007 tonsil tissue specimens were previously tested by enzyme immunoassay (EIA) for the presence of disease-related prion protein (PrPres) and found to be negative. To confirm the reliability of this result, all those in the birth cohort most at risk (1961–1985) and a few others, including controls, have now been tested by immunohistochemistry (IHC). Histological slides were prepared from 10 075 anonymized formalin-fixed, paraffin-embedded tissues and examined for PrPres with two anti-prion protein antibodies, ICMS35 and KG9. One specimen showed a single strongly positive follicle with both antibodies, on two slides from adjacent sections. As this specimen was negative when it was further investigated by EIA, IHC, and immunoblotting, it is unclear whether the patient from whom the tonsil came will go on to develop vCJD. If, however, this is the case, then a finding of 1 out of 9160 gives a prevalence of disease-related prion protein in the British population of 109 per million, with a 95% confidence interval (CI) of 3–608 per million, which is not statistically different (exact p = 0.63) from population prevalence estimates based on finding three positives out of 10 278 in a previous IHC study of appendix tissue. If this is not the case, a finding of 0 out of 9160 gives a prevalence of 0–403 per million (95% CI) for the 1961-1985 cohort, which is also not different (exact p = 0.25) from previous population prevalence estimates. Therefore, the results of this work could be summarized as finding, by IHC, no or one vCJD-positive individual.
Copyright © 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
http://onlinelibrary.wiley.com/doi/10.1002/path.2767/abstract
snip...
Discussion
Of the 9675 samples for which an IHC result was obtained, 9160 were in the 1961–1985 birth cohort. The remainder of the samples were selected for IHC because they showed some reactivity in the original serological screening of the 63 007 tonsils by EIA with Bio-Rad and Microsens kits [6]. In addition, there were three positive controls (sheep scrapie) among the 9675 samples submitted for IHC. Three samples (18 864, 38 660, and 40 751) gave IHC results that needed to be investigated more fully. Two of these IHC results were concluded to be background staining by three experts, while for the third it was concluded that there was one strongly positive follicle with both KG9 and ICSM35 antibodies. This could not be confirmed by analysis of slides made from further tissue samples embedded in wax, neither could it be confirmed by IB. This result raises the question of the significance and interpretation of a single positive follicle among the thousands from several sections that were examined, particularly in the light of the failure of IB to confirm the presence of PrPCJD in the tissue. Further investigation of tissue from this specimen by bioassay or protein misfolding cyclic amplification (PMCA) was considered not to be worthwhile because bioassay is unlikely to be more sensitive than enhanced chemiluminescent IB tests [11,25,27,28] and PMCA is insufficiently robust [29].
Our finding of one PrPres-positive follicle by IHC can be interpreted as showing that there is one individual in the 9160 samples from the 1961–1985 birth cohort who will go on to develop vCJD. Alternatively, if a single positive follicle is indicative of an insufficient amount of PrPres to spread and cause disease, the interpretation is that there is no one in the 9160 samples from the 1961–1985 birth cohort who will go on to develop vCJD. The decision between these two interpretations needs to be considered in the context of the relative sensitivities of the different tests that were used, and also in the context of the pathological significance of a small quantity of PrPres in a tonsil. Although all three methods (EIA, IB, and IHC) are based on the recognition of PrPres by specific anti- PrP antibodies, they are qualitatively and quantitatively different. As just a few stained cells can be seen by IHC, it could be argued that it is the more sensitive technique. Conversely, however, as a greater volume of tissue and therefore a larger number of cells can be tested by EIA and IB, it can be argued that they are the more sensitive methods [15]. However, the distribution of PrPres in the tissue is likely to be an important factor in assessing the comparative sensitivities of different tests: when there is a very focal deposition of PrPres, IHC may be assumed to have the advantage.
Therefore, while we cannot say whether the patient from whom this tissue came will go on to develop vCJD, we can be reasonably certain, however, that the patient has not yet developed disease as the codon 129 PRNP genotype is MV, and all probable and definite vCJD cases to date have been MM at this loci. There have been four ‘possible’ cases of clinical vCJD, one of which was MV, but this was not biochemically confirmed and it was in a different birth cohort from the person from whom the tonsil in our study came [30]. Also, the two IHC positives (out of three) from the previous study [26] for which a codon 129 genotype could be determined were PRNP codon 129VV [31] and no vCJD cases of this genotype have been reported.
The prevalence in the British population of underlying disease-related prion protein calculated from these findings is, if specimen 38 660 came from a vCJDpositive person, 109 per million for the 1961–1985 birth cohort, with a 95% confidence interval (CI) of 3–608 per million (Table 2), which is not different (exact p = 0.63) to the finding of three positives from 10 278 samples for the appendix survey [26]. If tonsil 38 660 did not come from a vCJD-positive person, then the prevalence is 0 per million with an upper 95% CI of 403 for the 1961–1985 cohort and 0 per million for the 1961–1995 cohort with an upper 95% CI of 394 (Table 2), which is not different (exact p = 0.25) from the previous study.
It is possible that infection arising from exposure to BSE could cause more than one type of prion disease [32–34]. Strains other than that resulting in vCJD, if they exist, may have markedly different pathogenesis, tissue distributions, and structural forms of PrPres. In addition, it is possible that genetic variability in the population may alter the pathogenesis of vCJD, in that the timing and rate of PrPres in appendix and tonsil tissues may differ between individuals. Indeed, genetic differences may even determine the extent of lymphoreticular pathogenesis [31].
Given that the collection of tonsils in our study has occurred later than the collection of appendix samples in the earlier appendix survey, it is conceivable that tonsils have been collected from infected individuals further into the incubation period than is the case for those individuals whose appendices were tested in the earlier survey [26]. Moreover, should the incubation period for prion disease be considerably longer in people with different genotypes, uncertainty about the timing of the appearance of detectable PrPres in these will increase, with concomitant implications for the interpretation of results of PrPres prevalence surveys [6].
Animal experiments have shown that high infectivity, and even disease, can be present in the absence of detectable PrPres [35]. However, this observation cannot be generalized, as PrPres has always been detectable in the lymphoid tissues that have been tested from vCJD patients [6,25,28]. Data from animal experiments also show ‘clearance’ of PrPres after inoculation [35,36]. Therefore, the PrPres found in the earlier survey of appendix tissue [26] may conceivably have been transient and eventually cleared without resulting in clinical disease, and therefore the result of the appendix survey result may not be replicable by the current tonsil survey [6].
Although, statistically, the vCJD prevalence estimates in this work do not differ significantly from those obtained by calculating from the previous Hilton study [26], qualitatively they suggest that prevalence estimates may be cautiously lowered. However, in an attempt to provide statistically significant evidence to demonstrate this, a large-scale IHC survey of recently collected appendix tissue specimens for the presence of PrPres is underway.
SEE FULL TEXT PDF ;
http://onlinelibrary.wiley.com/doi/10.1002/path.2767/pdf
Wednesday, June 29, 2011
TSEAC Meeting August 1, 2011 donor deferral Saudi Arabia vCJD risk blood and blood products
http://tseac.blogspot.com/2011/06/tseac-meeting-august-1-2011-donor.html
Saturday, April 30, 2011
Blood product, collected from a donor who was at risk for variant Creutzfeldt-Jakob disease (vCJD), was distributed APRIL 27, 2011
http://vcjdtransfusion.blogspot.com/2011/04/blood-product-collected-from-donor-who.html
Tuesday, December 14, 2010
Infection control of CJD, vCJD and other human prion diseases in healthcare and community settings part 4, Annex A1, Annex J, UPDATE DECEMBER 2010
http://creutzfeldt-jakob-disease.blogspot.com/2010/12/infection-control-of-cjd-vcjd-and-other.html
grinding bone ???
Monday, January 17, 2011
Aerosols Transmit Prions to Immunocompetent and Immunodeficient Mice
http://transmissiblespongiformencephalopathy.blogspot.com/2011/01/aerosols-transmit-prions-to.html
Tuesday, August 12, 2008
Biosafety in Microbiological and Biomedical Laboratories Fifth Edition 2007 (occupational exposure to prion diseases)
http://creutzfeldt-jakob-disease.blogspot.com/2008/08/biosafety-in-microbiological-and.html
High CJD infectivity remains after prion protein is destroyed
Kohtaro Miyazawa, Kaitlin Emmerling,
Laura Manuelidis DOI: 10.1002/jcb.23286
Copyright © 2011 Wiley-Liss, Inc.
Keywords: proteinase K; keratinase; Transmissible Spongiform Encephalopathies; scrapie; infectious particles; agent strains; cell culture
Abstract
The hypothesis that host prion protein (PrP) converts into an infectious prion form rests on the observation that infectivity progressively decreases in direct proportion to the decrease of PrP with proteinase K (PK) treatment. PrP that resists limited PK digestion (PrP-res, PrPsc) has been assumed to be the infectious form, with speculative types of misfolding encoding the many unique TSE agent strains. Recently, a PK sensitive form of PrP has been proposed as the prion. Thus we re-evaluated total PrP (sensitive and resistant) and used a cell-based assay for titration of infectious particles. A keratinase (NAP) known to effectively digest PrP was compared to PK. Total PrP in FU-CJD infected brain was reduced to =0.3% in a 2hr PK digest, yet there was no reduction in titer. Remaining non-PrP proteins were easily visualized with colloidal gold in this highly infectious homogenate. In contrast to PK, NAP digestion left 0.8% residual PrP after 2hr, yet decreased titer by >2.5logs; few residual protein bands remained. FU-CJD infected cells with 10x the infectivity of brain by both animal and cell culture assays were also evaluated. NAP again significantly reduced cell infectivity (>3.5 logs). Extreme PK digestions were needed to reduce cell PrP to <0.2%, yet a very high titer of =7.8 logs remained. Our FU-CJD brain results are in good accord with the only other report on maximal PrP digestion and titer. It is likely that one or more residual non-PrP proteins may protect agent nucleic acids in infectious particles. J. Cell. Biochem. © 2011 Wiley-Liss, Inc.
http://onlinelibrary.wiley.com/doi/10.1002/jcb.23286/abstract;jsessionid=96CE34EA74FE3FBC5D3538A7BB5B82A1.d02t03
comment ;
"Host prion protein (PrP) is commonly believed to change into an infectious prion form (PrPsc) that resists proteinase K (PK). This report shows that all forms of PrP can be destroyed with PK, yet huge amounts of the infectious agent survives. Resistant, non-PrP genomic molecules are most likely to encode the transmissible agent strains that incite persistent endemic and epidemic disease."
Laura Manuelidis end...TSS
Saturday, January 16, 2010
Evidence For CJD TSE Transmission Via Endoscopes 1-24-3 re-Singeltary to Bramble et al Evidence For CJD/TSE Transmission Via Endoscopes
http://creutzfeldt-jakob-disease.blogspot.com/2010/01/evidence-for-cjd-tse-transmission-via.html
Tuesday, March 29, 2011
TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY EXPOSURE SPREADING VIA HOSPITALS AND SURGICAL PROCEDURES AROUND THE GLOBE
http://transmissiblespongiformencephalopathy.blogspot.com/2011/03/transmissible-spongiform-encephalopathy.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
Tuesday, April 26, 2011
sporadic CJD RISING Text and figures of the latest annual report of the NCJDRSU covering the period 1990-2009 (published 11th March 2011)
http://creutzfeldt-jakob-disease.blogspot.com/2011/04/sporadic-cjd-rising-text-and-figures-of.html
Thursday, August 4, 2011
Terry Singeltary Sr. on the Creutzfeldt-Jakob Disease Public Health Crisis, Date aired: 27 Jun 2011
http://transmissiblespongiformencephalopathy.blogspot.com/2011/08/terry-singeltary-sr-on-creutzfeldt.html
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/pls/apex/f?p=2400:1001:5492868805159684::NO::F2400_P1001_BACK_PAGE,F2400_P1001_PUB_MAIL_ID:1000,86129
Thursday, July 28, 2011
An Update on the Animal Disease Traceability Framework July 27, 2011
http://naiscoolyes.blogspot.com/2011/07/update-on-animal-disease-traceability.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
RE - "BSE-L in North America may have existed for decades" YA THINK ???
Over the next 8-10 weeks, approximately 40% of all the adult mink on the farm died from TME.
snip...
The rancher was a ''dead stock'' feeder using mostly (>95%) downer or dead dairy cattle...
http://web.archive.org/web/20030516051623/http://www.bseinquiry.gov.uk/files/mb/m09/tab05.pdf
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
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
Thursday, July 21, 2011
A Second Case of Gerstmann-Sträussler-Scheinker Disease Linked to the G131V Mutation in the Prion Protein Gene in a Dutch Patient Journal of Neuropathology & Experimental Neurology:
August 2011 - Volume 70 - Issue 8 - pp 698-702
http://transmissiblespongiformencephalopathy.blogspot.com/2011/07/second-case-of-gerstmann-straussler.html
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
Wednesday, June 15, 2011
Galveston, Texas - Isle port moves through thousands of heifers headed to Russia, none from Texas, Alabama, or Washington, due to BSE risk factor
http://transmissiblespongiformencephalopathy.blogspot.com/2011/06/galveston-texas-isle-port-moves-through.html
TSS
For numbers of CJD case reports, readers should consult data provided by the National CJD Research and Surveillance Unit (NCJDRSU), Edinburgh [1]. The latest yearly analysis of vCJD reports (onsets and deaths) is also available from the NCJDRSU website [2].
Reports of incidents of potential iatrogenic exposure to CJD via surgery: 2000 to 30 June 2011.
A surgical incident occurs when a patient with or at increased risk of CJD has undergone surgery without the appropriate infection control guidance being followed [3]. This could happen if a patient undergoes surgery during the incubation period of CJD, or because information about CJD risk factors is not available at the time of surgery. If this happens, surgical instruments that may be contaminated with the infectious agent that causes CJD, could pose a transmission risk when they are re-used on other patients.
In June 2010 the CJD Incidents Panel changed its protocol for reporting surgical incidents, and a new reporting algorithm was published on the HPA CJD Section website. Under the new protocol only CJD cases (or patients at increased risk of CJD) who have undergone surgical procedures which are thought to pose a possible transmission risk (i.e. within the likely infectious incubation period, and involving medium or high risk procedures) are categorised as ‘surgical incidents'. Other procedures, either earlier in the incubation period, or involving low infectivity tissues, are categorised as ‘CJD Reports'.
Advice has been issued for one surgical incident and twelve CJD reports that have been reported to the CJD Incidents Panel in the first six months of 2011. Table 1 shows the number of CJD surgical incidents reported to the CJD Incidents Panel from 2000 to 30 June 2011 by the diagnosis of the index patient. As shown in the table, 45% of surgical incidents result from surgery on index cases diagnosed with sporadic CJD.
Information about the CJD Incidents Panel can be found on the HPA website [4].
Table 1: CJD surgical incidents (n=437) reported to the CJD Incidents Panel (which have been closed, or where advice has been issued) by diagnosis of index patient: 2000 to 30th June 2011 Index patient status '00 '01 '02 '03 '04 '05 '06 '07 '08 '09 '10 '11 Total incidents (% of total) Total CJD reports
Incid'ts Rep'ts Incid'ts Rep'ts Sporadic (possible, probable or definite) 7 19 22 24 16 18 31 17 21 15 5 4 1 12 196 (45%) 16
vCJD (possible, probable or definite) 6 14 22 5 4 1 2 – 1 – 56 (13%) –
Familial including 'at risk' familial – 2 7 1 3 7 – 2 3 2 – 29 (7%) –
'At risk' vCJD blood component recipient – 4 10 5 1 – 2 – 22 (5%) –
'At risk' - vCJD plasma product recipient – 1 2 – 10 18 9 8 6 9 3 – 66 (15%) –
'At risk' - other – 2 1 2 5 – 1 7 – 20 (5%) –
CJD type unclear/ CJD unlikely 1 – 4 1 2 – 10 (2%) –
Not CJD 2 1 4 7 1 – 3 – 1 – 27 (6%) –
Other – 1 2 1 – 1 – 7 (2%) –
No longer considered 'at-risk' – 1 – 1 – 2 – 4 (1%) –
Total 16 38 56 50 45 56 63 27 33 29 23 4 1 12 437 100% 16
Note: The totals in 2009 and 2010 have changed from those reported in February 2011 as incidents have been closed, or advice has been issued, since the database was archived for the February 2011 report.
If the investigation of a surgical incident identifies any instruments that are considered to be potentially contaminated with the infectious agent, and that could still pose an infection risk to other patients, the Panel advises that these instruments should be removed from general use or refurbished. These instruments may be quarantined, kept for exclusive use on the index patient, refurbished (endoscopes only) or destroyed.
Since 2000 there have been 84 incidents in which instruments have been permanently removed from general use or refurbished (endoscopes only). This is a reduction in the total given in the February 2011 report, as in 2011 the CJD Incidents Panel revised its advice on the re-use of endoscopes that had been through over ten cycles of re-use and decontamination, so that these endoscopes could be returned to general use. This resulted in the Panel revising its advice on endoscopes used in six incidents that were reported in 2010, so that in five of these incidents the Panel advised that none of the instruments involved needed to be removed from general use.
Surgical incidents resulting in ‘at risk’ patients
The Panel may advise contacting and informing patients of their possible exposure to CJD following a surgical incident. These patients should be considered 'at-risk of CJD for public health purposes' and are asked to take certain precautions (i.e. not to donate blood, other tissues or organs, and to inform their medical and dental carers prior to any invasive procedures) in order to reduce the risk of transmitting the CJD agent.
The diagnosis of the index patient; the timing of the procedure relative to the development of clinical CJD; the tissue that instruments were in contact with during the procedure on the index patient; and the number of cycles of re-use and decontamination the instruments have been through following the procedure on the index case – all influence the possible risk to subsequent patients.
The threshold level of risk at which patients are considered to be ‘at increased risk’ of CJD is 1%, in addition to the background risk in the UK population. This risk threshold is based on risk assessment models, using precautionary assumptions. The 1% threshold level is used as a cut off for implementing public health precautions and is not intended to be a precise measure of an individual patient's risk. A similar threshold is used for identifying other patients who have been exposed to possible CJD risks following surgical, blood, plasma and tissue incidents.
From 2000 to 30 June 2011, there have been 25 surgical incidents in which the Panel has advised that 179 patients should be considered to have an increased risk of CJD.
Patient denotifications
Following changes in the assessment of tissue infectivity, the Panel has advised that 38 patients in 14 surgical incidents who were originally considered (and notified) as being ‘at risk' of CJD should no longer be considered ‘at risk', and should be denotified. In November 2005, gastrointestinal endoscopies without invasive procedures were reclassified as low risk procedures, and advice was issued to denotify two patients in one surgical incident. In 2006, anterior eye was reclassified as a ‘medium low' infectivity tissue. This led to a change in advice as only the first patient on whom instruments were used following an anterior eye procedure was to be considered as having an increased risk of CJD. Previously this had applied to the first two patients exposed to such instruments. This resulted in the Panel advising that 16 patients in seven incidents should be denotified. In 2009, the anterior eye was further reclassified as a low infectivity tissue. Following this change, the Panel advised that 20 patients should be denotified.
As of 30 June 2011, the Panel has received confirmation that of the 34 patients originally notified of their exposure (out of the 38 originally considered to be ‘at risk'), 26 patients have been informed that they are no longer considered ‘at risk' and eight patients died before they could be denotified.
Current 'at risk' patients resulting from surgical instruments
There are 12 surgical incidents in which 141 patients are still considered to be at increased risk of CJD. Currently, 119 of these 'at risk' patients have been notified that they are at increased risk of CJD. Local decisions have been taken not to notify four patients in these incidents.
Table 2: Surgical ‘at risk’ patients still identified as being ‘at increased risk of CJD’ by the Panel by procedure on the index patient Diagnosis of index patient Procedure on index patient Number of incidents Patients identified as 'at risk' Patients who died before being notified Local decision not to notify patient Notified patients
Sporadic Brain biopsy 2 28 2 1 25
Variant Appendectomy 1 2 – 2 –
Variant Endoscopy 1 – 1 –
Asymptomatic infected vCJD Endoscopy 1 4 1 – 3
At risk variant Endoscopy 5 36 4 – 32
At risk familial Neurosurgery 1 31 10 – 21
At risk familial Ophthalmic surgery 1 39 1 – 38
Total
12 141 18 4 119
Monitoring of patients 'at increased risk' of CJD
The CJD Incidents Panel and the Advisory Committee on Dangerous Pathogens Transmissible Spongiform Encephalopathy Risk Management Subgroup (formerly the ACDP TSE Working Group) have identified a range of individuals and groups who may have been exposed to an increased risk of CJD as a consequence of their medical care (see table 3 below). The risks of iatrogenic CJD transmission to these different individuals are very uncertain, but potentially devastating. The CJD Incidents Panel has advised that these individuals should be informed of their risk and asked to follow public health precautions to avoid transmitting the infection to others.
It is important to follow up these individuals to help determine the risks of CJD spreading to patients through different routes. Follow up involves a range of activities and is carried out by different organisations. At core, follow up aims to ascertain whether any people who may have been exposed to increased CJD risks go on to develop CJD.
Table 3. Individuals at increased risk of CJD up to 30 June 2011 'At risk' Group Identified as 'at risk' Ever notified as being 'at risk' Alive and Notified Cases Asymptomatic infections
Recipients of blood from vCJD cases 66 27 18 3 1
Blood donors to vCJD cases 112 107 105 –
Other recipients from blood donors to vCJD cases 34 32 30 –
Plasma product recipients (all except one have non-bleeding disorders) 11 10 3 [c] –
Surgical contacts of all CJD cases 141 119 111 –
Highly transfused patients (recipients of blood from =80 donors identified at pre-surgical assessment) 7 6 5 –
Total for at risk groups where HPA holds data 371 301 273 3 1
Patients with bleeding disorders who received UK sourced plasma products [a] 3,840 n/k – 1
Recipients of human derived growth hormone [b] 1,883 Up to 1,883 Up to 1,527 64 –
Total for all 'at risk' groups [d] 6094 At least 2184 At least 1800 67 2
a. Data provided by the UK Haemophilia Centre Doctors' Organisation (UKHCDO). These are minimum figures. Central reporting for bleeding disorder patients is incomplete, and some patients have opted out of the central UKHCDO database. Individual haemophilia centres were asked to send out standardised letters of notification to all their ‘at risk’ patients, but the exact number of patients who received these letters and are therefore aware of their risk is not known. b. Data provided by the Institute for Child Health. A small number of ‘at risk' growth hormone recipients are not included in the Institute of Child Health study so the true number ‘at risk’ will be greater. The exact number of growth hormone recipients in the ICH study currently aware of their risk is not known, as given their age at the original notification many were informed indirectly, by their parents. c. The current status for one plasma ‘at risk' patient is under review by Health Protection Scotland. d. These are minimum figures given the comments made above.
Six-monthly update on the National Anonymous Tonsil Archive: end of July 2011
The National Anonymous Tonsil Archive (NATA) was set up in 2004 to prospectively collect 100,000 tonsils pairs obtained after routine tonsillectomies in England and Scotland and to test these samples for abnormal prion protein. Only tissue not required for patient care, which would normally be discarded, is collected. Tonsils are tested for abnormal prion protein by two commercial enzyme immunoassays (EIAs), and a small proportion selected for other analytical tests. Initial results from analysis of 63,007 of the tonsil samples, indicated that all tonsils were negative so far for the detection of PrPCJD protein [5].
Up to the end of July 2011, NATA has received a total of 94,611 tonsil pairs from hospitals in England and Scotland, about 17,849 of which are from the birth cohort in which most vCJD cases have arisen (1961-1985). A further 3,000 tonsil pairs have been received from the Medical Research Council Prion Unit at the UCL Institute for Neurology, National Hospital for Neurology and Neurosurgery. Therefore the total number of tonsil pairs in the archive as at the end of July 2011 was 96,949. The number of collection forms that were completed but where no tonsil tissue was collected was 2,541 (1,663 due to patient objection and 878 due to clinical pathology being requested).
Of the 100 NHS Hospital Trusts that perform over 200 tonsillectomies per year in England, 91 have been recruited and are currently sending tonsil pairs to NATA on a regular basis. There are 120 hospital sites within these trusts taking part in NATA. At present, approximately 50,000 tonsillectomies are performed annually in England. Figure 4 shows the number of tonsil pairs received from each Strategic Health Authority area.
Figure 1. Number of tonsil pairs collected for NATA quarterly (Q1, 2004 to Q3, 2011)
Figure 2. Tonsils pairs collected by Strategic Health Authority (January 2004 to July 2011)
Figure 3. NHS Trusts and Scottish hospitals currently collecting and sending tonsil tissue to the archive July 2011
References
1. The National Creutzfeldt-Jakob Disease Research and Surveillance Unit, The University of Edinburgh. CJD statistics. Available at: http://www.cjd.ed.ac.uk/figures.htm.
2. The National Creutzfeldt-Jakob Disease Research and Surveillance Unit, The University of Edinburgh. Incidence of variant Creutzfeldt-Jakob disease onsets and deaths in the UK January 1994 - May 2011. Edinburgh: NCJDSU, 18 May 2011. Available at: http://www.cjd.ed.ac.uk/cjdq68.pdf.
3. Transmissible spongiform encephalopathy agents: safe working and the prevention of infection. The ACDP TSE Risk Management Subgroup. http://www.dh.gov.uk/ab/ACDP/TSEguidance/index.htm.
4. HPA CJD Incidents Panel [online]. Available at: http://www.hpa.org.uk/web/ CJDIncidentsPanel.
5. Clewley J, Kelly CM, Andrews N, Vogliqi K, Mallinson G, Kaisar M, et al. Prevalence of disease related prion protein in anonymous tonsil specimens in Britain: cross sectional opportunistic survey. BMJ 2009; 338: b1442.
http://www.hpa.org.uk/hpr/infections/ei_cjd.htm
2008
POSITION STATEMENT PREVALENCE OF SUBCLINICAL VARIANT CREUTZFELDT-JAKOB DISEASE INFECTIONS
http://webarchive.nationalarchives.gov.uk/20110316162913/http://www.seac.gov.uk/statements/state-cjd-infections.pdf
2009
BMJ 2009; 338:b1442 doi: 10.1136/bmj.b1442 (Published 21 May 2009) Cite this as: BMJ 2009; 338:b1442 Research
Prevalence of disease related prion protein in anonymous tonsil specimens in Britain: cross sectional opportunistic survey
Jonathan P Clewley, clinical scientist1, Carole M Kelly, research epidemiologist1, Nick Andrews, statistician1, Kelly Vogliqi, research technician1, Gary Mallinson, clinical scientist2, Maria Kaisar, research scientist2, David A Hilton, consultant neuropathologist3, James W Ironside, professor of clinical neuropathology4, Philip Edwards, biomedical scientist3, Linda M McCardle, biomedical scientist4, Diane L Ritchie, research assistant4, Reza Dabaghian, research scientist1, Helen E Ambrose, research scientist1, O Noel Gill, consultant epidemiologist1
+ Author Affiliations
1Centre for Infections, Health Protection Agency, London NW9 5EQ
2Bristol Institute for Transfusion Sciences, National Blood Service, Bristol BS10 5ND
3Department of Histopathology, Derriford Hospital, Plymouth PL6 8DH
4National CJD Surveillance Unit, University of Edinburgh, Western General Hospital, Edinburgh EH4 2XU
Correspondence to: JP Clewley jonathan.clewley@hpa.org.uk Accepted 15 December 2008
Abstract
Objective
To establish with improved accuracy the prevalence of disease related prion protein (PrPCJD) in the population of Britain and thereby guide a proportionate public health response to limit the threat of healthcare associated transmission of variant Creutzfeldt-Jakob disease (vCJD).
Design Cross sectional opportunistic survey.
Study samples Anonymised tonsil pairs removed at elective tonsillectomy throughout England and Scotland.
Setting National anonymous tissue archive for England and Scotland.
Main outcome measure Presence of PrPCJD determined by using two enzyme immunoassays based on different analytical principles, with further investigation by immunohistochemistry or immunoblotting of any samples reactive in either assay.
Results Testing of 63007 samples was completed by the end of September 2008. Of these, 12753 were from the birth cohort in which most vCJD cases have arisen (1961-85) and 19908 were from the 1986-95 cohort that would have been also exposed to bovine spongiform encephalopathy through infected meat or meat products. None of the samples tested was unequivocally reactive in both enzyme immunoassays.
Only two samples were reactive in one or other enzyme immunoassay and equivocal in the other, and nine samples were equivocally reactive in both enzyme immunoassays.
Two hundred and seventy six samples were initially reactive in one or other enzyme immunoassay; the repeat reactivity rate was 15% or less, depending on the enzyme immunoassay and cut-off definition. None of the samples (including all the 276 initially reactive in enzyme immunoassay) that were investigated by immunohistochemistry or immunoblotting was positive for the presence of PrPCJD.
Conclusions The observed prevalence of PrPCJD in tonsils from the 1961-95 combined birth cohort was 0/32661 with a 95% confidence interval of 0 to 113 per million. In the 1961-85 cohort, the prevalence of zero with a 95% confidence interval of 0 to 289 per million was lower than, but still consistent with, a previous survey of appendix tissue that showed a prevalence of 292 per million with a 95% confidence interval of 60 to 853 per million. Continuing to archive and test tonsil specimens, especially in older birth cohorts, and other complementary large scale anonymous tissue surveys, particularly of post-mortem tissues, will further refine the calculated prevalence of PrPCJD.
http://www.bmj.com/content/338/bmj.b1442.full.pdf
2010
Large-scale immunohistochemical examination for lymphoreticular prion protein in tonsil specimens collected in Britain†
Mar Fernandez de Marco1, Jacqueline Linehan2, O Noel Gill3, Jonathan P Clewley3,*, Sebastian Brandner1,*Article first published online: 4 OCT 2010
DOI: 10.1002/path.2767
Keywords:variant Creutzfeldt–Jakob disease;bovine spongiform encephalopathy;vCJD prevalence;PrP
Abstract
There have been 173 cases of variant Creutzfeldt–Jakob disease (vCJD) in the UK, as of 5 July 2010, as a result of the bovine spongiform encephalopathy epidemic. The number of individuals subclinically infected with vCJD, and thus the eventual number of cases, remains, however, uncertain. In an attempt to address this problem, 63 007 tonsil tissue specimens were previously tested by enzyme immunoassay (EIA) for the presence of disease-related prion protein (PrPres) and found to be negative. To confirm the reliability of this result, all those in the birth cohort most at risk (1961–1985) and a few others, including controls, have now been tested by immunohistochemistry (IHC). Histological slides were prepared from 10 075 anonymized formalin-fixed, paraffin-embedded tissues and examined for PrPres with two anti-prion protein antibodies, ICMS35 and KG9. One specimen showed a single strongly positive follicle with both antibodies, on two slides from adjacent sections. As this specimen was negative when it was further investigated by EIA, IHC, and immunoblotting, it is unclear whether the patient from whom the tonsil came will go on to develop vCJD. If, however, this is the case, then a finding of 1 out of 9160 gives a prevalence of disease-related prion protein in the British population of 109 per million, with a 95% confidence interval (CI) of 3–608 per million, which is not statistically different (exact p = 0.63) from population prevalence estimates based on finding three positives out of 10 278 in a previous IHC study of appendix tissue. If this is not the case, a finding of 0 out of 9160 gives a prevalence of 0–403 per million (95% CI) for the 1961-1985 cohort, which is also not different (exact p = 0.25) from previous population prevalence estimates. Therefore, the results of this work could be summarized as finding, by IHC, no or one vCJD-positive individual.
Copyright © 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
http://onlinelibrary.wiley.com/doi/10.1002/path.2767/abstract
snip...
Discussion
Of the 9675 samples for which an IHC result was obtained, 9160 were in the 1961–1985 birth cohort. The remainder of the samples were selected for IHC because they showed some reactivity in the original serological screening of the 63 007 tonsils by EIA with Bio-Rad and Microsens kits [6]. In addition, there were three positive controls (sheep scrapie) among the 9675 samples submitted for IHC. Three samples (18 864, 38 660, and 40 751) gave IHC results that needed to be investigated more fully. Two of these IHC results were concluded to be background staining by three experts, while for the third it was concluded that there was one strongly positive follicle with both KG9 and ICSM35 antibodies. This could not be confirmed by analysis of slides made from further tissue samples embedded in wax, neither could it be confirmed by IB. This result raises the question of the significance and interpretation of a single positive follicle among the thousands from several sections that were examined, particularly in the light of the failure of IB to confirm the presence of PrPCJD in the tissue. Further investigation of tissue from this specimen by bioassay or protein misfolding cyclic amplification (PMCA) was considered not to be worthwhile because bioassay is unlikely to be more sensitive than enhanced chemiluminescent IB tests [11,25,27,28] and PMCA is insufficiently robust [29].
Our finding of one PrPres-positive follicle by IHC can be interpreted as showing that there is one individual in the 9160 samples from the 1961–1985 birth cohort who will go on to develop vCJD. Alternatively, if a single positive follicle is indicative of an insufficient amount of PrPres to spread and cause disease, the interpretation is that there is no one in the 9160 samples from the 1961–1985 birth cohort who will go on to develop vCJD. The decision between these two interpretations needs to be considered in the context of the relative sensitivities of the different tests that were used, and also in the context of the pathological significance of a small quantity of PrPres in a tonsil. Although all three methods (EIA, IB, and IHC) are based on the recognition of PrPres by specific anti- PrP antibodies, they are qualitatively and quantitatively different. As just a few stained cells can be seen by IHC, it could be argued that it is the more sensitive technique. Conversely, however, as a greater volume of tissue and therefore a larger number of cells can be tested by EIA and IB, it can be argued that they are the more sensitive methods [15]. However, the distribution of PrPres in the tissue is likely to be an important factor in assessing the comparative sensitivities of different tests: when there is a very focal deposition of PrPres, IHC may be assumed to have the advantage.
Therefore, while we cannot say whether the patient from whom this tissue came will go on to develop vCJD, we can be reasonably certain, however, that the patient has not yet developed disease as the codon 129 PRNP genotype is MV, and all probable and definite vCJD cases to date have been MM at this loci. There have been four ‘possible’ cases of clinical vCJD, one of which was MV, but this was not biochemically confirmed and it was in a different birth cohort from the person from whom the tonsil in our study came [30]. Also, the two IHC positives (out of three) from the previous study [26] for which a codon 129 genotype could be determined were PRNP codon 129VV [31] and no vCJD cases of this genotype have been reported.
The prevalence in the British population of underlying disease-related prion protein calculated from these findings is, if specimen 38 660 came from a vCJDpositive person, 109 per million for the 1961–1985 birth cohort, with a 95% confidence interval (CI) of 3–608 per million (Table 2), which is not different (exact p = 0.63) to the finding of three positives from 10 278 samples for the appendix survey [26]. If tonsil 38 660 did not come from a vCJD-positive person, then the prevalence is 0 per million with an upper 95% CI of 403 for the 1961–1985 cohort and 0 per million for the 1961–1995 cohort with an upper 95% CI of 394 (Table 2), which is not different (exact p = 0.25) from the previous study.
It is possible that infection arising from exposure to BSE could cause more than one type of prion disease [32–34]. Strains other than that resulting in vCJD, if they exist, may have markedly different pathogenesis, tissue distributions, and structural forms of PrPres. In addition, it is possible that genetic variability in the population may alter the pathogenesis of vCJD, in that the timing and rate of PrPres in appendix and tonsil tissues may differ between individuals. Indeed, genetic differences may even determine the extent of lymphoreticular pathogenesis [31].
Given that the collection of tonsils in our study has occurred later than the collection of appendix samples in the earlier appendix survey, it is conceivable that tonsils have been collected from infected individuals further into the incubation period than is the case for those individuals whose appendices were tested in the earlier survey [26]. Moreover, should the incubation period for prion disease be considerably longer in people with different genotypes, uncertainty about the timing of the appearance of detectable PrPres in these will increase, with concomitant implications for the interpretation of results of PrPres prevalence surveys [6].
Animal experiments have shown that high infectivity, and even disease, can be present in the absence of detectable PrPres [35]. However, this observation cannot be generalized, as PrPres has always been detectable in the lymphoid tissues that have been tested from vCJD patients [6,25,28]. Data from animal experiments also show ‘clearance’ of PrPres after inoculation [35,36]. Therefore, the PrPres found in the earlier survey of appendix tissue [26] may conceivably have been transient and eventually cleared without resulting in clinical disease, and therefore the result of the appendix survey result may not be replicable by the current tonsil survey [6].
Although, statistically, the vCJD prevalence estimates in this work do not differ significantly from those obtained by calculating from the previous Hilton study [26], qualitatively they suggest that prevalence estimates may be cautiously lowered. However, in an attempt to provide statistically significant evidence to demonstrate this, a large-scale IHC survey of recently collected appendix tissue specimens for the presence of PrPres is underway.
SEE FULL TEXT PDF ;
http://onlinelibrary.wiley.com/doi/10.1002/path.2767/pdf
Wednesday, June 29, 2011
TSEAC Meeting August 1, 2011 donor deferral Saudi Arabia vCJD risk blood and blood products
http://tseac.blogspot.com/2011/06/tseac-meeting-august-1-2011-donor.html
Saturday, April 30, 2011
Blood product, collected from a donor who was at risk for variant Creutzfeldt-Jakob disease (vCJD), was distributed APRIL 27, 2011
http://vcjdtransfusion.blogspot.com/2011/04/blood-product-collected-from-donor-who.html
Tuesday, December 14, 2010
Infection control of CJD, vCJD and other human prion diseases in healthcare and community settings part 4, Annex A1, Annex J, UPDATE DECEMBER 2010
http://creutzfeldt-jakob-disease.blogspot.com/2010/12/infection-control-of-cjd-vcjd-and-other.html
grinding bone ???
Monday, January 17, 2011
Aerosols Transmit Prions to Immunocompetent and Immunodeficient Mice
http://transmissiblespongiformencephalopathy.blogspot.com/2011/01/aerosols-transmit-prions-to.html
Tuesday, August 12, 2008
Biosafety in Microbiological and Biomedical Laboratories Fifth Edition 2007 (occupational exposure to prion diseases)
http://creutzfeldt-jakob-disease.blogspot.com/2008/08/biosafety-in-microbiological-and.html
High CJD infectivity remains after prion protein is destroyed
Kohtaro Miyazawa, Kaitlin Emmerling,
Laura Manuelidis DOI: 10.1002/jcb.23286
Copyright © 2011 Wiley-Liss, Inc.
Keywords: proteinase K; keratinase; Transmissible Spongiform Encephalopathies; scrapie; infectious particles; agent strains; cell culture
Abstract
The hypothesis that host prion protein (PrP) converts into an infectious prion form rests on the observation that infectivity progressively decreases in direct proportion to the decrease of PrP with proteinase K (PK) treatment. PrP that resists limited PK digestion (PrP-res, PrPsc) has been assumed to be the infectious form, with speculative types of misfolding encoding the many unique TSE agent strains. Recently, a PK sensitive form of PrP has been proposed as the prion. Thus we re-evaluated total PrP (sensitive and resistant) and used a cell-based assay for titration of infectious particles. A keratinase (NAP) known to effectively digest PrP was compared to PK. Total PrP in FU-CJD infected brain was reduced to =0.3% in a 2hr PK digest, yet there was no reduction in titer. Remaining non-PrP proteins were easily visualized with colloidal gold in this highly infectious homogenate. In contrast to PK, NAP digestion left 0.8% residual PrP after 2hr, yet decreased titer by >2.5logs; few residual protein bands remained. FU-CJD infected cells with 10x the infectivity of brain by both animal and cell culture assays were also evaluated. NAP again significantly reduced cell infectivity (>3.5 logs). Extreme PK digestions were needed to reduce cell PrP to <0.2%, yet a very high titer of =7.8 logs remained. Our FU-CJD brain results are in good accord with the only other report on maximal PrP digestion and titer. It is likely that one or more residual non-PrP proteins may protect agent nucleic acids in infectious particles. J. Cell. Biochem. © 2011 Wiley-Liss, Inc.
http://onlinelibrary.wiley.com/doi/10.1002/jcb.23286/abstract;jsessionid=96CE34EA74FE3FBC5D3538A7BB5B82A1.d02t03
comment ;
"Host prion protein (PrP) is commonly believed to change into an infectious prion form (PrPsc) that resists proteinase K (PK). This report shows that all forms of PrP can be destroyed with PK, yet huge amounts of the infectious agent survives. Resistant, non-PrP genomic molecules are most likely to encode the transmissible agent strains that incite persistent endemic and epidemic disease."
Laura Manuelidis end...TSS
Saturday, January 16, 2010
Evidence For CJD TSE Transmission Via Endoscopes 1-24-3 re-Singeltary to Bramble et al Evidence For CJD/TSE Transmission Via Endoscopes
http://creutzfeldt-jakob-disease.blogspot.com/2010/01/evidence-for-cjd-tse-transmission-via.html
Tuesday, March 29, 2011
TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY EXPOSURE SPREADING VIA HOSPITALS AND SURGICAL PROCEDURES AROUND THE GLOBE
http://transmissiblespongiformencephalopathy.blogspot.com/2011/03/transmissible-spongiform-encephalopathy.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
Tuesday, April 26, 2011
sporadic CJD RISING Text and figures of the latest annual report of the NCJDRSU covering the period 1990-2009 (published 11th March 2011)
http://creutzfeldt-jakob-disease.blogspot.com/2011/04/sporadic-cjd-rising-text-and-figures-of.html
Thursday, August 4, 2011
Terry Singeltary Sr. on the Creutzfeldt-Jakob Disease Public Health Crisis, Date aired: 27 Jun 2011
http://transmissiblespongiformencephalopathy.blogspot.com/2011/08/terry-singeltary-sr-on-creutzfeldt.html
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/pls/apex/f?p=2400:1001:5492868805159684::NO::F2400_P1001_BACK_PAGE,F2400_P1001_PUB_MAIL_ID:1000,86129
Thursday, July 28, 2011
An Update on the Animal Disease Traceability Framework July 27, 2011
http://naiscoolyes.blogspot.com/2011/07/update-on-animal-disease-traceability.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
RE - "BSE-L in North America may have existed for decades" YA THINK ???
Over the next 8-10 weeks, approximately 40% of all the adult mink on the farm died from TME.
snip...
The rancher was a ''dead stock'' feeder using mostly (>95%) downer or dead dairy cattle...
http://web.archive.org/web/20030516051623/http://www.bseinquiry.gov.uk/files/mb/m09/tab05.pdf
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
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
Thursday, July 21, 2011
A Second Case of Gerstmann-Sträussler-Scheinker Disease Linked to the G131V Mutation in the Prion Protein Gene in a Dutch Patient Journal of Neuropathology & Experimental Neurology:
August 2011 - Volume 70 - Issue 8 - pp 698-702
http://transmissiblespongiformencephalopathy.blogspot.com/2011/07/second-case-of-gerstmann-straussler.html
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
Wednesday, June 15, 2011
Galveston, Texas - Isle port moves through thousands of heifers headed to Russia, none from Texas, Alabama, or Washington, due to BSE risk factor
http://transmissiblespongiformencephalopathy.blogspot.com/2011/06/galveston-texas-isle-port-moves-through.html
TSS
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