All Clinically-Relevant Blood Components Transmit Prion Disease following a Single Blood Transfusion: A Sheep Model of vCJD
Sandra McCutcheon1., Anthony Richard Alejo Blanco1., E. Fiona Houston2., Christopher de Wolf1, Boon Chin Tan1, Antony Smith3, Martin H. Groschup4, Nora Hunter1, Valerie S. Hornsey5, Ian R. MacGregor5, Christopher V. Prowse5, Marc Turner6, Jean C. Manson1* 1 The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Roslin, Edinburgh, United Kingdom, 2 School of Veterinary Medicine, College of Medical, Veterinary and Life Sciences, The University of Glasgow, Glasgow, United Kingdom, 3 The Institute for Animal Health, Compton, Berkshire, United Kingdom, 4 Institute for Novel and Emerging Infectious Diseases, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Germany, 5 National Science Laboratory, Scottish National Blood Transfusion Service (SNBTS), Edinburgh, United Kingdom, 6 University of Edinburgh and SNBTS, Edinburgh, United Kingdom
Abstract
Variant CJD (vCJD) is an incurable, infectious human disease, likely arising from the consumption of BSE-contaminated meat products. Whilst the epidemic appears to be waning, there is much concern that vCJD infection may be perpetuated in humans by the transfusion of contaminated blood products. Since 2004, several cases of transfusion-associated vCJD transmission have been reported and linked to blood collected from pre-clinically affected donors. Using an animal model in which the disease manifested resembles that of humans affected with vCJD, we examined which blood components used in human medicine are likely to pose the greatest risk of transmitting vCJD via transfusion. We collected two full units of blood from BSE-infected donor animals during the pre-clinical phase of infection. Using methods employed by transfusion services we prepared red cell concentrates, plasma and platelets units (including leucoreduced equivalents). Following transfusion, we showed that all components contain sufficient levels of infectivity to cause disease following only a single transfusion and also that leucoreduction did not prevent disease transmission. These data suggest that all blood components are vectors for prion disease transmission, and highlight the importance of multiple control measures to minimise the risk of human to human transmission of vCJD by blood transfusion.
Citation: McCutcheon S, Alejo Blanco AR, Houston EF, de Wolf C, Tan BC, et al. (2011) All Clinically-Relevant Blood Components Transmit Prion Disease following a Single Blood Transfusion: A Sheep Model of vCJD. PLoS ONE 6(8): e23169. doi:10.1371/journal.pone.0023169 Editor: Matthew Baylis, University of Liverpool, United Kingdom Received March 17, 2011; Accepted July 8, 2011; Published August 17, 2011 Copyright: 2011 McCutcheon et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This is an independent report commissioned and funded by the Policy Research Programme in the Department of Health, UK (007/0162). The views expressed in the publication are those of the authors and not necessarily those of the Department of Health. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. * E-mail: jean.manson@roslin.ed.ac.uk . These authors contributed equally to this work
snip...
Discussion
We have shown that all of the blood components investigated, whole blood, plasma, red cells, platelets and buffy coat, are capable of transmitting BSE infection following transfusion into susceptible sheep. Although infectivity has consistently been detected in plasma in rodent scrapie models, this is the first time that transmission of prion disease has been demonstrated following transfusion of plasma units collected from pre-clinical donors, and prepared to the same specifications as non-fractionated human plasma. While the results with platelets and leucocytes are similar to that of Mathiason et al. [30], the plasma results are strikingly different. In the previous study, prion infected cell-free plasma appeared not to cause disease following transfusion in deer. The reason for this is not clear and may relate to either a difference in the distribution of PrPSc and/or infectivity in different host species or indeed the strain of infectious agent used.
We also observed a number of cases in which leucoreduced components have caused BSE in recipients following transfusion. Other recipients of leucoreduced components are also now showing early signs of TSE infection and we would therefore expect more positive transmissions of BSE from these components. These data demonstrate that leucoreduction of blood components alone is insufficient to prevent transmission of prion infection via blood transfusion [23]. All four of the documented transfusionrelated transmissions of vCJD infectivity to date have occurred in individuals who received red cells (the most commonly transfused blood component) which were non-leucoreduced, between 1996 and 1999. Eighteen surviving recipients [36] transfused with red blood cells (n= 6), cryodepleted plasma (n =1) and leucoreduced red blood cells (n =11) from donors who were subsequently confirmed to have vCJD are still being followed up (personal communication from Miss J. McKenzie and Prof. R.G. Will, TMER study). There are a small number of cases of clinical vCJD with a history of blood transfusion, where no donor has developed clinical vCJD but where transfusion remains the possible source of infection. The most recent of these cases (2002) received leucoreduced red cells. Our findings would suggest that residual infectivity following leucoreduction may still pose a risk of transmission in a transfusion setting [23,37,38].
These transfusion studies were conducted in sheep, in which many effects of polymorphisms associated with the prnp gene (which modulates susceptibility to prion infection) are well understood. Similarly, the age at which donors and recipients were exposed to BSE prions, the infectious dose (in donor sheep) and the route of infection were relatively well controlled. Despite the control of known variables within this experiment, we observed significant variability in the incubation period of both orally infected donors and transfused recipients. During the course of this study we identified a novel effect of an existing polymorphism in the sheep PRNP gene, which modulates the incubation period of orally infected BSE donors (unpublished observations). While some of the variability in incubation periods of transfused recipients is likely associated with other genetic factors [39,40,41], it is also likely to be influenced by variability in prion titre in blood from donor sheep. It must also be recognised that in this model, incubation period is not considered an indicator of titre of infectivity in blood, since a full titration of infected blood has not yet been undertaken in sheep. However, given that BSE occurred in recipients following a single blood transfusion from donors who were healthy at the time of blood donation, we would suggest that even when or if the infectious load is low, disease can result if the route of transmission, i.e. blood transfusion, is highly efficient. Whilst we have clearly shown that blood collected from donor animals at a single time point is infectious, what remains unclear is when prion-associated infectivity first appears in blood, how it relates to incubation period and how the titre of infection changes as disease progresses. We are investigating these questions by inoculating transgenic mice with blood collected at various time points throughout the incubation period, from the same donor sheep as used in this study. This will allow us to address the duration, pattern and titre of prion infectivity in blood.
Our data raises considerable questions concerning the distribution of infectivity in blood, including its potential association with cell types other than leucocytes i.e. red cells and platelets, and/or other proteins or soluble components of plasma. Our data relating to the current transmission efficiencies of each component suggest whole blood and buffy coat represent the greatest risk in terms of transfusion and blood safety. However, these data may change over the full time course of this study and therefore it is too early to draw definitive conclusions. Furthermore, the blood components used in this study (including leucoreduced equivalents) were not purified cell populations, but also contained plasma and leucocytes to reflect the nature of the components routinely transfused in human patients. This may complicate understanding the process of identifying the relationship between the infectious agent and cell targets. It is also possible that mechanisms such as release of membrane fractions during processing [42] or shedding/transit by plasma membrane-derived microvesicles [43,44] may also contribute to the dissemination of infectivity in blood. It will be critical to understand how prion infectivity associates with particular blood components, and may identify new targets for diagnostics, therapeutics and allow for more refined risk reduction strategies.
Whilst these findings highlight the difficulties in predicting incubation times and the clinical outcomes associated with transfusion-related transmission of vCJD in humans (because of the extensive variability of individuals in terms of age, genetic background, titre and route by which one could be exposed) these data have clear implications for transfusion practices. We demonstrate the potential risk of acquiring vCJD from any blood component used in routine transfusion medicine, following a single transfusion from asymptomatic individuals.
While there has been recent, significant, developments in the quest for a blood-based assay to detect prion infection in symptomatic individuals [45], implementing such assays in the blood transfusion service to detect asymptomatic donors requires extensive validation. Thus there currently remains the potential for human to human transmission of vCJD via blood transfusion from individuals carrying the infectious agent but not showing clinical signs of disease. Our data suggests that leucoreduction alone is inadequate to minimise the risk of transmission of vCJD and to ensure the safety of blood used in transfusions and ultimately to safeguard public health.
http://www.plosone.org/article/fetchObjectAttachment.action?uri=info%3Adoi%2F10.1371%2Fjournal.pone.0023169&representation=PDF
http://www.plosone.org/article/fetchArticle.action;jsessionid=198F52B91A67C1A9520EB62354DB5D93.ambra01?utm_medium=feed&utm_campaign=Feed%3A+plosone%2FPLoSONE+(PLoS+ONE+Alerts%3A+New+Articles)&utm_source=feedburner&articleURI=info%3Adoi%2F10.1371%2Fjournal.pone.0023169
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
FC5.1.1
Transmission Results in Squirrel Monkeys Inoculated with Human sCJD, vCJD, and GSS Blood Specimens: the Baxter Study
Brown, P1; Gibson, S2; Williams, L3; Ironside, J4; Will, R4; Kreil, T5; Abee, C3 1Fondation Alliance BioSecure, France; 2University of South Alabama, USA; 3University of Texas MD Anderson Cancer Center, USA; 4Western General Hospital, UK; 5Baxter BioSience, Austria
Background: Rodent and sheep models of Transmissible Spongiform Encephalopathy (TSE) have documented blood infectivity in both the pre-clinical and clinical phases of disease. Results in a (presumably more appropriate) non-human primate model have not been reported.
Objective: To determine if blood components (red cells, white cells, platelets, and plasma) from various forms of human TSE are infectious.
Methods: Blood components were inoculated intra-cerebrally (0.1 ml) and intravenously (0.5 ml) into squirrel monkeys from 2 patients with sporadic Creutzfeldt- Jakob disease (sCJD) and 3 patients with variant Creutzfeldt-Jakob disease (vCJD). Additional monkeys were inoculated with buffy coat or plasma samples from chimpanzees infected with either sCJD or Gerstmann-Sträussler-Scheinker disease (GSS). Animals were monitored for a period of 5 years, and all dying or sacrificed animals had post-mortem neuropathological examinations and Western blots to determine the presence or absence of the misfolded prion protein (PrPTSE).
Results: No transmissions occurred in any of the animals inoculated with blood components from patients with sporadic or variant CJD. All donor chimpanzees (sCJD and GSS) became symptomatic within 6 weeks of their pre-clinical phase plasmapheresis, several months earlier than the expected onset of illness. One monkey inoculated with purified leukocytes from a pre-clinical GSS chimpanzee developed disease after 36 months.
Conclusion: No infectivity was found in small volumes of blood components from 4 patients with sporadic CJD and 3 patients with variant CJD. ***However, a single transmission from a chimpanzee-passaged strain of GSS shows that infectivity may be present in leukocytes, and the shock of general anaesthesia and plasmspheresis appears to have triggered the onset of illness in pre-clinical donor chimpanzees.
Saturday, September 5, 2009
TSEAC MEETING FEBRUARY 12, 2004 THE BAXTER STUDY GSS
snip...
http://tseac.blogspot.com/2011/06/tseac-meeting-august-1-2011-donor.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
Sunday, August 21, 2011
The British disease, or a disease gone global, The TSE Prion Disease
http://transmissiblespongiformencephalopathy.blogspot.com/2011/08/british-disease-or-disease-gone-global.html
Thursday, August 4, 2011
Terry Singeltary Sr. on the Creutzfeldt-Jakob Disease Public Health Crisis, Date aired: 27 Jun 2011
see video here ;
http://transmissiblespongiformencephalopathy.blogspot.com/2011/08/terry-singeltary-sr-on-creutzfeldt.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
Sunday, August 21, 2011
Classical Bovine Spongiform Encephalopathy by Transmission of H-Type Prion in Homologous Prion Protein Context
Volume 17, Number 9-September 2011
Research
http://transmissiblespongiformencephalopathy.blogspot.com/2011/08/classical-bovine-spongiform.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
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
UPDATE TSE PRION DISEASE NORTH AMERICA...FOR YOU INFORMATION, things you might not be aware of...TSS
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
UPDATED DATA ON 2ND CWD STRAIN
Wednesday, September 08, 2010
CWD PRION CONGRESS SEPTEMBER 8-11 2010
http://chronic-wasting-disease.blogspot.com/2010/09/cwd-prion-2010.html
Wednesday, January 5, 2011
ENLARGING SPECTRUM OF PRION-LIKE DISEASES Prusiner Colby et al 2011
Prions
David W. Colby1,* and Stanley B. Prusiner1,2
http://betaamyloidcjd.blogspot.com/2011/01/enlarging-spectrum-of-prion-like.html
Wednesday, July 06, 2011
Swine Are Susceptible to Chronic Wasting Disease by Intracerebral Inoculation
http://chronic-wasting-disease.blogspot.com/2011/07/swine-are-susceptible-to-chronic.html
Thursday, April 03, 2008
A prion disease of cervids: Chronic wasting disease
2008 1: Vet Res. 2008 Apr 3;39(4):41
A prion disease of cervids: Chronic wasting disease
Sigurdson CJ.
snip...
*** twenty-seven CJD patients who regularly consumed venison were reported to the Surveillance Center***,
snip...
full text ;
http://chronic-wasting-disease.blogspot.com/2008/04/prion-disease-of-cervids-chronic.html
1989
IN CONFIDENCE
Perceptions of unconventional slow virus diseases of animals in the USA
Spraker suggested an interesting explanation for the occurrence of CWD. The deer pens at the Foot Hills Campus were built some 30-40 years ago by a Dr. Bob Davis. At or about that time, allegedly, some scrapie work was conducted at this site. When deer were introduced to the pens they occupied ground that had previously been occupied by sheep. Whether they were scrapie infected sheep or not is unclear.
http://collections.europarchive.org/tna/20080102193705/http://www.bseinquiry.gov.uk/files/mb/m11b/tab01.pdf
http://wildlife.state.co.us/NR/rdonlyres/C82EB818-90C6-4D85-897E-9CE279546CCB/0/JWDEpiCWD.pdf
CJD9/10022
October 1994
Mr R.N. Elmhirst Chairman British Deer Farmers Association Holly Lodge Spencers Lane BerksWell Coventry CV7 7BZ
Dear Mr Elmhirst,
CREUTZFELDT-JAKOB DISEASE (CJD) SURVEILLANCE UNIT REPORT
Thank you for your recent letter concerning the publication of the third annual report from the CJD Surveillance Unit. I am sorry that you are dissatisfied with the way in which this report was published.
The Surveillance Unit is a completely independant outside body and the Department of Health is committed to publishing their reports as soon as they become available. In the circumstances it is not the practice to circulate the report for comment since the findings of the report would not be amended. In future we can ensure that the British Deer Farmers Association receives a copy of the report in advance of publication.
The Chief Medical Officer has undertaken to keep the public fully informed of the results of any research in respect of CJD. This report was entirely the work of the unit and was produced completely independantly of the the Department.
The statistical results reqarding the consumption of venison was put into perspective in the body of the report and was not mentioned at all in the press release. Media attention regarding this report was low key but gave a realistic presentation of the statistical findings of the Unit. This approach to publication was successful in that consumption of venison was highlighted only once by the media ie. in the News at one television proqramme.
I believe that a further statement about the report, or indeed statistical links between CJD and consumption of venison, would increase, and quite possibly give damaging credence, to the whole issue. From the low key media reports of which I am aware it seems unlikely that venison consumption will suffer adversely, if at all.
http://web.archive.org/web/20030511010117/http://www.bseinquiry.gov.uk/files/yb/1994/10/00003001.pdf
Sunday, July 03, 2011
Prion Disease Detection, PMCA Kinetics, and IgG in Urine from Naturally/Experimentally Infected Scrapie Sheep and Preclinical/Clinical CWD Deer
http://chronic-wasting-disease.blogspot.com/2011/07/prion-disease-detection-pmca-kinetics.html
PLUS, THE CDC DID NOT PUT THIS WARNING OUT FOR THE WELL BEING OF THE DEER AND ELK ;
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
NOR IS THE FDA recalling this CWD positive elk meat for the well being of the dead elk ;
Wednesday, March 18, 2009
Noah's Ark Holding, LLC, Dawson, MN RECALL Elk products contain meat derived from an elk confirmed to have CWD NV, CA, TX, CO, NY, UT, FL, OK RECALLS AND FIELD CORRECTIONS: FOODS CLASS II
http://chronic-wasting-disease.blogspot.com/2009/03/noahs-ark-holding-llc-dawson-mn-recall.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
TSS
Wednesday, August 24, 2011
Tuesday, August 23, 2011
Creating plastic from beef and what about those pesky prions TSE mad cow agent ?
Creating plastic from beef and what about those pesky prions TSE mad cow agent ?
Creating plastic from beef
By Bev Betkowski
August 12, 2011
(Edmonton) They look a little like fake cookies, the kind you’d find in a child’s toy oven, but the chocolate brown plastic discs created by University of Alberta researcher David Bressler and his lab represent the future of ingenious recycling.
Using the throwaway parts of beef carcasses that were sidelined from the value-added production process after bovine spongiform encephalopathy devastated the industry in 2003, Bressler, an associate professor in the U of A’s Department of Agricultural, Food and Nutritional Science has collaborated with industry, government and other researchers to forge cattle proteins into heavy-duty plastics that could soon be used in everything from car parts to CD cases.
The University of Alberta is the only post-secondary facility to be approved by the Canada Food Inspection Agency to conduct research involving turning high-risk proteins into safe, sustainable materials.
By finding a way to convert these animal byproducts into plastics for industrial use, Bressler and his team, which also includes Phillip Choi, a professor in the U of A’s Faculty of Engineering, hope to divert tonnes of protein waste from landfills across North America, shift to using renewable resources instead of petrochemicals to make plastics, and boost flagging profit levels in the cattle industry.
Beef producers took an economic hit when byproducts such as blood and bone were regulated out of the rendering process after BSE was found in Canada, for fear the material contained deadly prions—infectious proteins that cause BSE, more commonly known as mad cow disease.
“If we can get more fundamental value back into the rendering process, it will help the livestock industry more than any government policy,” Bressler says.
A patent has been filed on the thermal process used to turn protein from bovine byproducts into plastics. Using high temperatures, the proteins are broken into small pieces then cross-linked to other protein molecules to create a network that forms a rigid structure.
The new plastics from Bressler’s lab are currently being tested by The Woodbridge group, a car parts manufacturer. Current funding is focused on research that further experiments with the product, to see if the plastics can be mixed with renewable fibres such as hemp. If successful, the resulting bio-composite material could be used in high-strength materials such as building structural supports.
The bio-friendly plastics, though still in the development stage, are poised to become an innovative addition to the manufacturing industry, Bressler believes. “The plastic industry is under pressure to increase the renewable content in its products. As a result, this project offers the opportunity to do just that, and at the same time help send value back to rural Alberta and the beef sector.”
Bressler’s work is supported by the Alberta Prion Research Institute, PrioNet Canada and the Alberta Livestock and Meat Agency.
http://www.research.ualberta.ca/en/VP%20Research%20News/2011/08/Creatingplasticfrombeef.aspx
Prion Infected Meat-and-Bone Meal Is Still Infectious after Biodiesel Production
Cathrin E. Bruederle,1* Robert M. Hnasko,1 Thomas Kraemer,2 Rafael A. Garcia,3 Michael J. Haas,3 William N. Marmer,3 and John Mark Carter1 1USDA-ARS WRRC, Foodborne Contaminants Research Unit, Albany, California, United States of America 2Forensic Toxicology, Institute of Legal Medicine, Saarland University, Homburg/Saar, Germany 3USDA-ARS ERRC, Fats, Oils and Animal Coproducts Research Unit, Wyndmoor, Pennsylvania, United States of America Neil Mabbott, EditorUniversity of Edinburgh, United Kingdom *
E-mail: cathrin.bruederle@gmail.comConceived and designed the experiments: CEB RMH WNM JMC. Performed the experiments: CEB RMH TK. Analyzed the data: CEB TK JMC. Contributed reagents/materials/analysis tools: CEB RMH TK RAG MJH JMC. Wrote the paper: CEB. Received April 21, 2008; Accepted July 24, 2008. Other Sections?
Abstract
The epidemic of bovine spongiform encephalopathy (BSE) has led to a world-wide drop in the market for beef by-products, such as Meat-and-Bone Meal (MBM), a fat-containing but mainly proteinaceaous product traditionally used as an animal feed supplement. While normal rendering is insufficient, the production of biodiesel from MBM has been suggested to destroy infectivity from transmissible spongiform encephalopathies (TSEs). In addition to producing fuel, this method simultaneously generates a nutritious solid residue. In our study we produced biodiesel from MBM under defined conditions using a modified form of alkaline methanolysis. We evaluated the presence of prion in the three resulting phases of the biodiesel reaction (Biodiesel, Glycerol and Solid Residue) in vitro and in vivo. Analysis of the reaction products from 263K scrapie infected MBM led to no detectable immunoreactivity by Western Blot. Importantly, and in contrast to the biochemical results the solid MBM residue from the reaction retained infectivity when tested in an animal bioassay. Histochemical analysis of hamster brains inoculated with the solid residue showed typical spongiform degeneration and vacuolation. Re-inoculation of these brains into a new cohort of hamsters led to onset of clinical scrapie symptoms within 75 days, suggesting that the specific infectivity of the prion protein was not changed during the biodiesel process. The biodiesel reaction cannot be considered a viable prion decontamination method for MBM, although we observed increased survival time of hamsters and reduced infectivity greater than 6 log orders in the solid MBM residue. Furthermore, results from our study compare for the first time prion detection by Western Blot versus an infectivity bioassay for analysis of biodiesel reaction products. We could show that biochemical analysis alone is insufficient for detection of prion infectivity after a biodiesel process.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2493038/
New studies on the heat resistance of hamster-adapted scrapie agent: Threshold survival after ashing at 600°C suggests an inorganic template of replication
Paul Brown*,dagger , Edward H. RauDagger , Bruce K. Johnson*, Alfred E. Bacote*, Clarence J. Gibbs Jr.*, and D. Carleton Gajdusek§ * Laboratory of Central Nervous System Studies, National Institute of Neurological Disorders and Stroke, and Dagger Environmental Protection Branch, Division of Safety, Office of Research Services, National Institutes of Health, Bethesda, MD 20892; and § Institut Alfred Fessard, Centre National de la Recherche Scientifique, 91198 Gif sur Yvette, France Contributed by D. Carleton Gajdusek, December 22, 1999
Abstract
One-gram samples from a pool of crude brain tissue from hamsters infected with the 263K strain of hamster-adapted scrapie agent were placed in covered quartz-glass crucibles and exposed for either 5 or 15 min to dry heat at temperatures ranging from 150°C to 1,000°C. Residual infectivity in the treated samples was assayed by the intracerebral inoculation of dilution series into healthy weanling hamsters, which were observed for 10 months; disease transmissions were verified by Western blot testing for proteinase-resistant protein in brains from clinically positive hamsters. Unheated control tissue contained 9.9 log10LD50/g tissue; after exposure to 150°C, titers equaled or exceeded 6 log10LD50/g, and after exposure to 300°C, titers equaled or exceeded 4 log10LD50/g. Exposure to 600°C completely ashed the brain samples, which, when reconstituted with saline to their original weights, transmitted disease to 5 of 35 inoculated hamsters. No transmissions occurred after exposure to 1,000°C. These results suggest that an inorganic molecular template with a decomposition point near 600°C is capable of nucleating the biological replication of the scrapie agent. transmissible spongiform encephalopathy | scrapie | prion | medical waste | incineration Introduction The infectious agents responsible for transmissible spongiform encephalopathy (TSE) are notoriously resistant to most physical and chemical methods used for inactivating pathogens, including heat. It has long been recognized, for example, that boiling is ineffective and that higher temperatures are most efficient when combined with steam under pressure (i.e., autoclaving). As a means of decontamination, dry heat is used only at the extremely high temperatures achieved during incineration, usually in excess of 600°C. It has been assumed, without proof, that incineration totally inactivates the agents of TSE, whether of human or animal origin. It also has been assumed that the replication of these agents is a strictly biological process (1), although the notion of a "virus" nucleant of an inorganic molecular cast of the infectious beta -pleated peptide also has been advanced (2). In this paper, we address these issues by means of dry heat inactivation studies.
see full text:
http://www.pnas.org/cgi/content/full/97/7/3418
P04.61
Survival of PrPSc during Simulated Wastewater Treatment Processes
Pedersen, J1; Hinckley, G1; McMahon, K2; McKenzie, D3; Aiken, JM3 1University of Wisconsin, Soil Science/Civil and Environmental Engineering, USA; 2University of Wisconsin, Civil and Environmental Engineering, USA; 3University of Wisconsin, Comparative Biosciences, USA
Concern has been expressed that prions could enter wastewater treatment systems through sewer and/or septic systems (e.g., necropsy laboratories, rural meat processors, private game dressing) or through leachate from landfills that have received TSE-contaminated material. Prions are highly resistant to degradation and many disinfection procedures raising concern that they could survive conventional wastewater treatment. Here, we report the results of experiments examining the partitioning and survival of PrPSc during simulated wastewater treatment processes including activated and mesophilic anaerobic sludge digestion. We establish that PrPSc can be efficiently extracted from activated and anaerobic digester sludges with 1% sodium dodecyl sulfate, 10% sodium undecyl sulfate, and 1% sodium N-lauryl sarcosinate. Activated sludge digestion does not result in significant degradation of PrPSc. The protein partitions strongly to the activated sludge solids and is expected to enter biosolids treatment processes. A large fraction of PrPSc survived simulated mesophilic anaerobic sludge digestion. Our results suggest that if prions were to enter municipal waste water treatment systems, most of the agent would partition to activated sludge solids, survive mesophilic anaerobic digestion, and be present in treated biosolids. Land application of biosolids containing prions could represent a route for their unintentional introduction into the environment. Our results argue for excluding inputs of prions to municipal wastewater treatment facilities that would result in unacceptable risk of prion disease transmission via contaminated biosolids.
snip...end....NEUROPRION 2007
http://www.neuroprion.com/pdf_docs/conferences/prion2007/abstract_book.pdf
PPo4-4:
Survival and Limited Spread of TSE Infectivity after Burial
Karen Fernie, Allister Smith and Robert A. Somerville The Roslin Institute and R(D)SVS; University of Edinburgh; Roslin, Scotland UK
Scrapie and chronic wasting disease probably spread via environmental routes, and there are also concerns about BSE infection remaining in the environment after carcass burial or waste 3disposal. In two demonstration experiments we are determining survival and migration of TSE infectivity when buried for up to five years, as an uncontained point source or within bovine heads. Firstly boluses of TSE infected mouse brain were buried in lysimeters containing either sandy or clay soil. Migration from the boluses is being assessed from soil cores taken over time. With the exception of a very small amount of infectivity found 25 cm from the bolus in sandy soil after 12 months, no other infectivity has been detected up to three years. Secondly, ten bovine heads were spiked with TSE infected mouse brain and buried in the two soil types. Pairs of heads have been exhumed annually and assessed for infectivity within and around them. After one year and after two years, infectivity was detected in most intracranial samples and in some of the soil samples taken from immediately surrounding the heads. The infectivity assays for the samples in and around the heads exhumed at years three and four are underway. These data show that TSE infectivity can survive burial for long periods but migrates slowly. Risk assessments should take into account the likely long survival rate when infected material has been buried.
The authors gratefully acknowledge funding from DEFRA.
PPo8-13:
Degradation of Pathogenic Prion Protein and Prion Infectivity by Lichens
Christopher J. Johnson,1 James P. Bennett,1 Steven M. Biro,1,2 Cynthia M. Rodriguez,1,2 Richard A. Bessen3 and Tonie E. Rocke1
1USGS National Wildlife Health Center; 2Department of Bacteriology; University of Wisconsin, Madison; 3Department of Veterinary Molecular Biology; Montana State University; Bozeman, MT USA
Key words: prion, lichen, bioassay, protease, degradation
Few biological systems have been identified that degrade the transmissible spongiform encephalopathy (TSE)-associated form of the prion protein (PrPTSE) and TSE infectivity. Stability of the TSE agent allows scrapie and chronic wasting disease agents to persist in the environment and cause disease for years. Naturally-occurring or engineered processes that reduce infectivity in the environment could aid in limiting environmental TSE transmission. We have previously identified that species of at least three lichens, unusual, symbiotic organisms formed from a fungus and photosynthetic partner, contain a serine protease capable of degrading PrPTSE under gentle conditions. We tested the hypothesis that lichen extracts from these three species reduce TSE infectivity by treating infected brain homogenate with extracts and examining infectivity in mice. We found lichen extracts diminished TSE infectious titer by factors of 100 to 1,000 and that reductions in infectivity were not well-correlated with the extent of PrPTSE degradation observed by immunoblotting. For example, treatment of brain homogenate with Cladonia rangiferina extract caused <100-fold reduction in PrP immunoreactivity but ~1,000-fold decrease in infectivity, suggesting that some PrPTSE remaining after extract treatment was rendered uninfectious or that the lichen protease favors more infectious forms of PrPTSE. Our data also indicate that lichen species closely related to those with prion-degrading protease activity do not necessarily degrade PrPTSE. Characterization of the lichen species-specificity of PrPTSE degradation within the genera Cladonia and Usnea and comparison with known lichen phylogeny has yielded clusters of species on which to focus searches for anti-prion agents.
http://chronic-wasting-disease.blogspot.com/2010/09/cwd-prion-2010.html
infectivity surviving ashing to 600*C is (in my opinion) degradable but infective. based on Bown & Gajdusek, (1991), landfill and burial may be assumed to have a reduction factor of 98% (i.e. a factor of 50) over 3 years. CJD-infected brain-tissue remained infectious after storing at room-temperature for 22 months (Tateishi et al, 1988). Scrapie agent is known to remain viable after at least 30 months of desiccation (Wilson et al, 1950). and pastures that had been grazed by scrapie-infected sheep still appeared to be contaminated with scrapie agent three years after they were last occupied by sheep (Palsson, 1979).
http://europa.eu.int/comm/food/fs/sc/ssc/out58_en.pdf
PAUL BROWN SCRAPIE SOIL TEST
http://collections.europarchive.org/tna/20080102120203/http://www.bseinquiry.gov.uk/files/sc/seac07/tab03.pdf
i suppose my question would be, would any Transmissible Spongiform Encephalopathy TSE prion aka mad cow type disease agent survive the production of any said product ??? and then the question of raising one of Gods living, breathing, animals, as a material to build with, as opposed as a gift from God as a source of food, and the ethical or moral aspect of it all, there from...oh hell, never mind, that went out the window a long time ago when factory farming came about. it's all about money now, so heck with it, build a dashboard for your car with prions in it, put a damn boom box in it, and hope for the best, who cares anymore $$$ i am sure that is what God intended...NOT!
stupid is, as stupid does, and some times you just can't fix stupid. ...
TSS
'soyent green'.
see ;
Soylent Green is a 1973 dystopian science fiction movie depicting a future in which overpopulation lead to depleted resources, which in turn leads to widespread unemployment and poverty. Real fruit, vegetables, and meat are rare, commodities are expensive, and much of the population survives on processed food rations, including "soylent green" wafers.
The film overlays the science fiction and police procedural genres as it depicts the efforts of New York City police detective Robert Thorn (Charlton Heston) and elderly police researcher Sol Roth (Edward G. Robinson) to investigate the brutal murder of a wealthy businessman named William R. Simonson (Joseph Cotten). Thorn and Roth uncover clues which suggest that it is more than simply a bungled burglary.
snip...
After Roth dies, Thorn sneaks into the basement of the government-assisted suicide facility, where he sees corpses being loaded onto waste disposal trucks. He secretly hitches a ride on one of the trucks, which is driven to a heavily guarded waste disposal plant. Once inside the plant, Thorn sees how the corpses are processed into Soylent Green wafers. After Thorn escapes from the plant and heads for the supreme exchange with the information, he is ambushed by Fielding and several other gunmen. In the shootout, Thorn kills some of the gunmen, but is himself wounded. He retreats into a cathedral filled with homeless people. After a desperate fight, Thorn stabs and kills Fielding.
When police backup arrives, the seriously wounded and nearly hysterical Thorn confides to Hatcher the horrible secret behind Soylent Green and urges him to spread the word: "Soylent Green is people! We've got to stop them somehow!"
http://en.wikipedia.org/wiki/Soylent_Green
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, February 26, 2011
Supreme Court Protects Vaccine Manufacturers, Not Injured Children there from Bruesewitz vs Wyeth
http://vcjdtransfusion.blogspot.com/2011/02/supreme-court-protects-vaccine.html
Sunday, August 21, 2011
The British disease, or a disease gone global, The TSE Prion Disease
http://transmissiblespongiformencephalopathy.blogspot.com/2011/08/british-disease-or-disease-gone-global.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
TSS
Creating plastic from beef
By Bev Betkowski
August 12, 2011
(Edmonton) They look a little like fake cookies, the kind you’d find in a child’s toy oven, but the chocolate brown plastic discs created by University of Alberta researcher David Bressler and his lab represent the future of ingenious recycling.
Using the throwaway parts of beef carcasses that were sidelined from the value-added production process after bovine spongiform encephalopathy devastated the industry in 2003, Bressler, an associate professor in the U of A’s Department of Agricultural, Food and Nutritional Science has collaborated with industry, government and other researchers to forge cattle proteins into heavy-duty plastics that could soon be used in everything from car parts to CD cases.
The University of Alberta is the only post-secondary facility to be approved by the Canada Food Inspection Agency to conduct research involving turning high-risk proteins into safe, sustainable materials.
By finding a way to convert these animal byproducts into plastics for industrial use, Bressler and his team, which also includes Phillip Choi, a professor in the U of A’s Faculty of Engineering, hope to divert tonnes of protein waste from landfills across North America, shift to using renewable resources instead of petrochemicals to make plastics, and boost flagging profit levels in the cattle industry.
Beef producers took an economic hit when byproducts such as blood and bone were regulated out of the rendering process after BSE was found in Canada, for fear the material contained deadly prions—infectious proteins that cause BSE, more commonly known as mad cow disease.
“If we can get more fundamental value back into the rendering process, it will help the livestock industry more than any government policy,” Bressler says.
A patent has been filed on the thermal process used to turn protein from bovine byproducts into plastics. Using high temperatures, the proteins are broken into small pieces then cross-linked to other protein molecules to create a network that forms a rigid structure.
The new plastics from Bressler’s lab are currently being tested by The Woodbridge group, a car parts manufacturer. Current funding is focused on research that further experiments with the product, to see if the plastics can be mixed with renewable fibres such as hemp. If successful, the resulting bio-composite material could be used in high-strength materials such as building structural supports.
The bio-friendly plastics, though still in the development stage, are poised to become an innovative addition to the manufacturing industry, Bressler believes. “The plastic industry is under pressure to increase the renewable content in its products. As a result, this project offers the opportunity to do just that, and at the same time help send value back to rural Alberta and the beef sector.”
Bressler’s work is supported by the Alberta Prion Research Institute, PrioNet Canada and the Alberta Livestock and Meat Agency.
http://www.research.ualberta.ca/en/VP%20Research%20News/2011/08/Creatingplasticfrombeef.aspx
Prion Infected Meat-and-Bone Meal Is Still Infectious after Biodiesel Production
Cathrin E. Bruederle,1* Robert M. Hnasko,1 Thomas Kraemer,2 Rafael A. Garcia,3 Michael J. Haas,3 William N. Marmer,3 and John Mark Carter1 1USDA-ARS WRRC, Foodborne Contaminants Research Unit, Albany, California, United States of America 2Forensic Toxicology, Institute of Legal Medicine, Saarland University, Homburg/Saar, Germany 3USDA-ARS ERRC, Fats, Oils and Animal Coproducts Research Unit, Wyndmoor, Pennsylvania, United States of America Neil Mabbott, EditorUniversity of Edinburgh, United Kingdom *
E-mail: cathrin.bruederle@gmail.comConceived and designed the experiments: CEB RMH WNM JMC. Performed the experiments: CEB RMH TK. Analyzed the data: CEB TK JMC. Contributed reagents/materials/analysis tools: CEB RMH TK RAG MJH JMC. Wrote the paper: CEB. Received April 21, 2008; Accepted July 24, 2008. Other Sections?
Abstract
The epidemic of bovine spongiform encephalopathy (BSE) has led to a world-wide drop in the market for beef by-products, such as Meat-and-Bone Meal (MBM), a fat-containing but mainly proteinaceaous product traditionally used as an animal feed supplement. While normal rendering is insufficient, the production of biodiesel from MBM has been suggested to destroy infectivity from transmissible spongiform encephalopathies (TSEs). In addition to producing fuel, this method simultaneously generates a nutritious solid residue. In our study we produced biodiesel from MBM under defined conditions using a modified form of alkaline methanolysis. We evaluated the presence of prion in the three resulting phases of the biodiesel reaction (Biodiesel, Glycerol and Solid Residue) in vitro and in vivo. Analysis of the reaction products from 263K scrapie infected MBM led to no detectable immunoreactivity by Western Blot. Importantly, and in contrast to the biochemical results the solid MBM residue from the reaction retained infectivity when tested in an animal bioassay. Histochemical analysis of hamster brains inoculated with the solid residue showed typical spongiform degeneration and vacuolation. Re-inoculation of these brains into a new cohort of hamsters led to onset of clinical scrapie symptoms within 75 days, suggesting that the specific infectivity of the prion protein was not changed during the biodiesel process. The biodiesel reaction cannot be considered a viable prion decontamination method for MBM, although we observed increased survival time of hamsters and reduced infectivity greater than 6 log orders in the solid MBM residue. Furthermore, results from our study compare for the first time prion detection by Western Blot versus an infectivity bioassay for analysis of biodiesel reaction products. We could show that biochemical analysis alone is insufficient for detection of prion infectivity after a biodiesel process.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2493038/
New studies on the heat resistance of hamster-adapted scrapie agent: Threshold survival after ashing at 600°C suggests an inorganic template of replication
Paul Brown*,dagger , Edward H. RauDagger , Bruce K. Johnson*, Alfred E. Bacote*, Clarence J. Gibbs Jr.*, and D. Carleton Gajdusek§ * Laboratory of Central Nervous System Studies, National Institute of Neurological Disorders and Stroke, and Dagger Environmental Protection Branch, Division of Safety, Office of Research Services, National Institutes of Health, Bethesda, MD 20892; and § Institut Alfred Fessard, Centre National de la Recherche Scientifique, 91198 Gif sur Yvette, France Contributed by D. Carleton Gajdusek, December 22, 1999
Abstract
One-gram samples from a pool of crude brain tissue from hamsters infected with the 263K strain of hamster-adapted scrapie agent were placed in covered quartz-glass crucibles and exposed for either 5 or 15 min to dry heat at temperatures ranging from 150°C to 1,000°C. Residual infectivity in the treated samples was assayed by the intracerebral inoculation of dilution series into healthy weanling hamsters, which were observed for 10 months; disease transmissions were verified by Western blot testing for proteinase-resistant protein in brains from clinically positive hamsters. Unheated control tissue contained 9.9 log10LD50/g tissue; after exposure to 150°C, titers equaled or exceeded 6 log10LD50/g, and after exposure to 300°C, titers equaled or exceeded 4 log10LD50/g. Exposure to 600°C completely ashed the brain samples, which, when reconstituted with saline to their original weights, transmitted disease to 5 of 35 inoculated hamsters. No transmissions occurred after exposure to 1,000°C. These results suggest that an inorganic molecular template with a decomposition point near 600°C is capable of nucleating the biological replication of the scrapie agent. transmissible spongiform encephalopathy | scrapie | prion | medical waste | incineration Introduction The infectious agents responsible for transmissible spongiform encephalopathy (TSE) are notoriously resistant to most physical and chemical methods used for inactivating pathogens, including heat. It has long been recognized, for example, that boiling is ineffective and that higher temperatures are most efficient when combined with steam under pressure (i.e., autoclaving). As a means of decontamination, dry heat is used only at the extremely high temperatures achieved during incineration, usually in excess of 600°C. It has been assumed, without proof, that incineration totally inactivates the agents of TSE, whether of human or animal origin. It also has been assumed that the replication of these agents is a strictly biological process (1), although the notion of a "virus" nucleant of an inorganic molecular cast of the infectious beta -pleated peptide also has been advanced (2). In this paper, we address these issues by means of dry heat inactivation studies.
see full text:
http://www.pnas.org/cgi/content/full/97/7/3418
P04.61
Survival of PrPSc during Simulated Wastewater Treatment Processes
Pedersen, J1; Hinckley, G1; McMahon, K2; McKenzie, D3; Aiken, JM3 1University of Wisconsin, Soil Science/Civil and Environmental Engineering, USA; 2University of Wisconsin, Civil and Environmental Engineering, USA; 3University of Wisconsin, Comparative Biosciences, USA
Concern has been expressed that prions could enter wastewater treatment systems through sewer and/or septic systems (e.g., necropsy laboratories, rural meat processors, private game dressing) or through leachate from landfills that have received TSE-contaminated material. Prions are highly resistant to degradation and many disinfection procedures raising concern that they could survive conventional wastewater treatment. Here, we report the results of experiments examining the partitioning and survival of PrPSc during simulated wastewater treatment processes including activated and mesophilic anaerobic sludge digestion. We establish that PrPSc can be efficiently extracted from activated and anaerobic digester sludges with 1% sodium dodecyl sulfate, 10% sodium undecyl sulfate, and 1% sodium N-lauryl sarcosinate. Activated sludge digestion does not result in significant degradation of PrPSc. The protein partitions strongly to the activated sludge solids and is expected to enter biosolids treatment processes. A large fraction of PrPSc survived simulated mesophilic anaerobic sludge digestion. Our results suggest that if prions were to enter municipal waste water treatment systems, most of the agent would partition to activated sludge solids, survive mesophilic anaerobic digestion, and be present in treated biosolids. Land application of biosolids containing prions could represent a route for their unintentional introduction into the environment. Our results argue for excluding inputs of prions to municipal wastewater treatment facilities that would result in unacceptable risk of prion disease transmission via contaminated biosolids.
snip...end....NEUROPRION 2007
http://www.neuroprion.com/pdf_docs/conferences/prion2007/abstract_book.pdf
PPo4-4:
Survival and Limited Spread of TSE Infectivity after Burial
Karen Fernie, Allister Smith and Robert A. Somerville The Roslin Institute and R(D)SVS; University of Edinburgh; Roslin, Scotland UK
Scrapie and chronic wasting disease probably spread via environmental routes, and there are also concerns about BSE infection remaining in the environment after carcass burial or waste 3disposal. In two demonstration experiments we are determining survival and migration of TSE infectivity when buried for up to five years, as an uncontained point source or within bovine heads. Firstly boluses of TSE infected mouse brain were buried in lysimeters containing either sandy or clay soil. Migration from the boluses is being assessed from soil cores taken over time. With the exception of a very small amount of infectivity found 25 cm from the bolus in sandy soil after 12 months, no other infectivity has been detected up to three years. Secondly, ten bovine heads were spiked with TSE infected mouse brain and buried in the two soil types. Pairs of heads have been exhumed annually and assessed for infectivity within and around them. After one year and after two years, infectivity was detected in most intracranial samples and in some of the soil samples taken from immediately surrounding the heads. The infectivity assays for the samples in and around the heads exhumed at years three and four are underway. These data show that TSE infectivity can survive burial for long periods but migrates slowly. Risk assessments should take into account the likely long survival rate when infected material has been buried.
The authors gratefully acknowledge funding from DEFRA.
PPo8-13:
Degradation of Pathogenic Prion Protein and Prion Infectivity by Lichens
Christopher J. Johnson,1 James P. Bennett,1 Steven M. Biro,1,2 Cynthia M. Rodriguez,1,2 Richard A. Bessen3 and Tonie E. Rocke1
1USGS National Wildlife Health Center; 2Department of Bacteriology; University of Wisconsin, Madison; 3Department of Veterinary Molecular Biology; Montana State University; Bozeman, MT USA
Key words: prion, lichen, bioassay, protease, degradation
Few biological systems have been identified that degrade the transmissible spongiform encephalopathy (TSE)-associated form of the prion protein (PrPTSE) and TSE infectivity. Stability of the TSE agent allows scrapie and chronic wasting disease agents to persist in the environment and cause disease for years. Naturally-occurring or engineered processes that reduce infectivity in the environment could aid in limiting environmental TSE transmission. We have previously identified that species of at least three lichens, unusual, symbiotic organisms formed from a fungus and photosynthetic partner, contain a serine protease capable of degrading PrPTSE under gentle conditions. We tested the hypothesis that lichen extracts from these three species reduce TSE infectivity by treating infected brain homogenate with extracts and examining infectivity in mice. We found lichen extracts diminished TSE infectious titer by factors of 100 to 1,000 and that reductions in infectivity were not well-correlated with the extent of PrPTSE degradation observed by immunoblotting. For example, treatment of brain homogenate with Cladonia rangiferina extract caused <100-fold reduction in PrP immunoreactivity but ~1,000-fold decrease in infectivity, suggesting that some PrPTSE remaining after extract treatment was rendered uninfectious or that the lichen protease favors more infectious forms of PrPTSE. Our data also indicate that lichen species closely related to those with prion-degrading protease activity do not necessarily degrade PrPTSE. Characterization of the lichen species-specificity of PrPTSE degradation within the genera Cladonia and Usnea and comparison with known lichen phylogeny has yielded clusters of species on which to focus searches for anti-prion agents.
http://chronic-wasting-disease.blogspot.com/2010/09/cwd-prion-2010.html
infectivity surviving ashing to 600*C is (in my opinion) degradable but infective. based on Bown & Gajdusek, (1991), landfill and burial may be assumed to have a reduction factor of 98% (i.e. a factor of 50) over 3 years. CJD-infected brain-tissue remained infectious after storing at room-temperature for 22 months (Tateishi et al, 1988). Scrapie agent is known to remain viable after at least 30 months of desiccation (Wilson et al, 1950). and pastures that had been grazed by scrapie-infected sheep still appeared to be contaminated with scrapie agent three years after they were last occupied by sheep (Palsson, 1979).
http://europa.eu.int/comm/food/fs/sc/ssc/out58_en.pdf
PAUL BROWN SCRAPIE SOIL TEST
http://collections.europarchive.org/tna/20080102120203/http://www.bseinquiry.gov.uk/files/sc/seac07/tab03.pdf
i suppose my question would be, would any Transmissible Spongiform Encephalopathy TSE prion aka mad cow type disease agent survive the production of any said product ??? and then the question of raising one of Gods living, breathing, animals, as a material to build with, as opposed as a gift from God as a source of food, and the ethical or moral aspect of it all, there from...oh hell, never mind, that went out the window a long time ago when factory farming came about. it's all about money now, so heck with it, build a dashboard for your car with prions in it, put a damn boom box in it, and hope for the best, who cares anymore $$$ i am sure that is what God intended...NOT!
stupid is, as stupid does, and some times you just can't fix stupid. ...
TSS
'soyent green'.
see ;
Soylent Green is a 1973 dystopian science fiction movie depicting a future in which overpopulation lead to depleted resources, which in turn leads to widespread unemployment and poverty. Real fruit, vegetables, and meat are rare, commodities are expensive, and much of the population survives on processed food rations, including "soylent green" wafers.
The film overlays the science fiction and police procedural genres as it depicts the efforts of New York City police detective Robert Thorn (Charlton Heston) and elderly police researcher Sol Roth (Edward G. Robinson) to investigate the brutal murder of a wealthy businessman named William R. Simonson (Joseph Cotten). Thorn and Roth uncover clues which suggest that it is more than simply a bungled burglary.
snip...
After Roth dies, Thorn sneaks into the basement of the government-assisted suicide facility, where he sees corpses being loaded onto waste disposal trucks. He secretly hitches a ride on one of the trucks, which is driven to a heavily guarded waste disposal plant. Once inside the plant, Thorn sees how the corpses are processed into Soylent Green wafers. After Thorn escapes from the plant and heads for the supreme exchange with the information, he is ambushed by Fielding and several other gunmen. In the shootout, Thorn kills some of the gunmen, but is himself wounded. He retreats into a cathedral filled with homeless people. After a desperate fight, Thorn stabs and kills Fielding.
When police backup arrives, the seriously wounded and nearly hysterical Thorn confides to Hatcher the horrible secret behind Soylent Green and urges him to spread the word: "Soylent Green is people! We've got to stop them somehow!"
http://en.wikipedia.org/wiki/Soylent_Green
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, February 26, 2011
Supreme Court Protects Vaccine Manufacturers, Not Injured Children there from Bruesewitz vs Wyeth
http://vcjdtransfusion.blogspot.com/2011/02/supreme-court-protects-vaccine.html
Sunday, August 21, 2011
The British disease, or a disease gone global, The TSE Prion Disease
http://transmissiblespongiformencephalopathy.blogspot.com/2011/08/british-disease-or-disease-gone-global.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
TSS
Sunday, August 21, 2011
The British disease, or a disease gone global, The TSE Prion Disease
The British disease, or a disease gone global, The TSE Prion Disease
(CJD...see old video here from EU)
see new url here ;
http://zoomify.uzh.ch:8080/zoomify/videos/video-009/video-009.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
Sunday, August 21, 2011
Classical Bovine Spongiform Encephalopathy by Transmission of H-Type Prion in Homologous Prion Protein Context
Volume 17, Number 9–September 2011
Research
http://transmissiblespongiformencephalopathy.blogspot.com/2011/08/classical-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
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
Risk.16: Clinical Disease in Cattle Experimentally Inoculated with All Types of BSE
Catherine Graham,1,† Michel Levy,2 Ed Pajor,2 Garth McGregor,1 Rheana Flitton1 and Stefanie Czub1
1Canadian Food Inspection Agency; Lethbridge, AB Canada; 2Faculty of Veterinary Medicine; University of Calgary; Calgary, AB Canada†Presenting author; Email: catherine.graham@inspection.gc.ca
Background. Classical, or C-type, bovine spongiform encephalopathy (BSE) has been extensively described in the literature. Recently, two novel forms of BSE, termed atypical BSE, have been reported in a number of countries. These new forms show differences in the biochemical characteristics of the prion protein and, where reported, tend to occur in aged animals but descriptions of clinical presentation are incomplete or absent.
Materials and Methods. Female Hereford/Angus cross calves were intracranially challenged at approximately five months of age with 1 ml of a 10% brain homogenate originating from Canadian field cases of BSE which had been previously classified as C-, L-, or H- type.
The animals were monitored during incubation period, and clinical disease is described using a standardized examination protocol. Incubation period, description and progression of clinical signs was recorded and videotaped for objective evaluation.
Results. All L- and H- type atypical BSE challenged animals began to display signs of clinical disease at approximately 11 months post inoculation, and disease progression was slow but constant until animals were euthanized. Clinical signs in all atypical BSE inoculated animals included hesitation at doors and gates, spontaneous muscle fasciculations and sensitivity to touch. Teeth grinding and excessive salivation are occasionally noted. Animals with L-type BSE are very anxious and show high levels of sensitivity to hand movement. One H-type animal shows periods of somnolence. Both H-type inoculated animals go down during handling and have difficulty rising and show sensitivity to movement around their head and neck area, but to a lesser degree than the L-type BSE inoculated animals. Interestingly, no locomotor abnormalities have been observed in either group.
C-type challenged animals remain normal at approximately 18 months post inoculation. Clinical disease in C-type inoculated animals from a previous transmission study was typically slow and intermittently displayed during the initial stages and after a period of two to four months was more consistent and progressive. Clinical signs in C-type BSE were as previously reported in the literature.
Discussion. The spectrum of clinical signs for all three types of BSE examined is similar. Incubation period is shorter for H- and L-type BSE as compared with C-type. Once clinical signs begin, progression is slow but relentless in atypical BSE, and more insidious in classical BSE. A summary of clinical signs presented in the three different types of BSE will be presented, and video of clinical disease will be displayed.
http://www.prion2011.ca/files/PRION_2011_-_Posters_(May_5-11).pdf
Risk.04: Demographic and Diagnostic Differences in Minorities with Sporadic Creutzfeldt-Jakob Disease
Brian S. Appleby,1,† Kristin K. Appleby2, 3 and Mitchell T. Wallin2
1Johns Hopkins University School of Medicine; Baltimore, MD USA; 2Veterans Affairs Medical Center; Washington, DC USA; 3Parkinson’s and Movement Disorders Center of Maryland; Elkridge, MD USA†Presenting author; Email: bappleb1@jhmi.edu
Sporadic Creutzfeldt-Jakob disease (sCJD) is the most common form of human prion disease. Prior epidemiologic studies of CJD in the U.S.A have reported a lower age adjusted incidence rate for blacks compared to whites. The goal of this study was to explore possible demographic and diagnostic features that could explain this finding.
Method. Previously collected data from Johns Hopkins and the Veterans Affairs Health Care System (VHS) between 1995-2007 were analyzed in this study following IRB approval. Only probable and definite cases of sCJD were included in the final analyses. Caucasian and Hispanic subjects were characterized as white and all other ethnicities were considered non-white in analyses. Chi-square analyses were used for categorical variables and Kaplan-Meier analyses were used for continuous variables.
Results. 116 subjects [n = 100 (86.2%) Caucasian, n = 6 (5.2%) black, n = 6 (5.2%) Hispanic, and n = 4 (3.4%) other race] were included in this study. Age at disease onset differed significantly between whites (mean = 65.2 ± 0.89 years) and non-whites (mean = 57.8 ± 2.94 years) (Log Rank = 5.32, p = 0.021). The correct clinical diagnosis was determined more rapidly in non-whites (46.7 ± 19.5 days) compared to whites (197.3 ± 35.6 days) (Log Rank = 7.08, p = 0.008). Although tissue diagnosis did not differ significantly between groups, non-whites were less likely to undergo autopsy (1/10, 10%) compared to whites (51/103, 49.5%) (Fisher’s exact test, 2-sided, p = 0.02).
Conclusions. In this study population, non-whites had an earlier age at disease onset compared to whites. Non-whites also received the correct clinical diagnosis more quickly compared to whites and were less likely to undergo autopsy. Given these results, it is unclear if non-whites truly have a younger age at onset compared to whites as this may be the result of ascertainment bias. The much more rapid clinical diagnosis of non-whites suggests that a diagnosis of CJD was considered earlier in non-whites who had an earlier age at disease onset. The decreased autopsy rate of non-whites is also concerning as this may falsely lower the estimated incidence of sCJD in non-whites in epidemiologic studies that rely heavily on neuropathologic data. Further studies examining the incidence and diagnostic process of sCJD in non-whites is needed. This study also demonstrates the importance of including patients that are diagnosed clinically and who do not undergo autopsies in CJD surveillance efforts.
Risk.06: Could National Mortality Registers Provide Reliable Indicators for Creutzfeldt-Jakob Disease Surveillance? A Study in France from the 2000-2008 Mortality Data
Jean-Philippe Brandel,1, 5, 7,† Arlette Welaratne,1 Dominique Salomon,2, 7 Isabelle Capek,3 Véronique Vaillant,3 Albertine Aouba,4 Stéphane Haïk5, 7, 1 and Annick Alpérovitch2, 8
1APHP Groupe Hospitalier Pitié Salpêtrière; Paris, France; 2INSERM U708 Neuroepidemiology; Paris, France; 3Institut de Veille Sanitaire; Saint Maurice, France; 4INSERM CépiDc; Le Vésinet, France; 5INSERM UMR-S 975 Equipe maladie d’Alzheimer-maladies à prions; Paris, France; 6CNRS UMR 7225; Paris, France; 7Université Pierre et Marie Curie-Paris; Paris, France†Presenting author; Email: jean-philippe.brandel@psl.aphp.fr
Active surveillance of Creutzfeldt-Jakob disease, which has been implemented in European countries, requires important human resources and funding. As the epidemic of variant CJD due to the bovine spongiform encephalopathy agent is in decline, less intense surveillance systems, based on routine mortality or morbidity registers, could be considered. CJD data collected by the French national CJD surveillance centre were compared with CJD data registered in the national mortality statistics. From
2000 to 2008, the two sources reported fairly similar numbers of CJD deaths (1188 and 1221 for the surveillance centre and the mortality register respectively). However, analysis of individual data showed important between-sources disagreements. At least 13% of CJD reported by the mortality register were false positive diagnoses and 21.6% of the CJD cases diagnosed by the surveillance centre were not registered as CJD in the national mortality statistics. For 126 deaths registered as CJD in the mortality statistics that had not been notified to the surveillance center, available data did not allow CJD diagnosis to be confirmed or excluded. One out of 22 variant CJD cases was not reported as having any type of CJD in the mortality statistics. Without further investigation, the conclusion could have been that CJD surveillance could be based on routinely collected mortality data. Considering the uncertainties on the evolution of the vCJD epidemics and the emergence of novel prion diseases in animals consumed by humans with zoonotic potential, these results support the idea that an active surveillance should be maintained to provide reliable data on future cases that may arise in next decades.
Risk.10: CSF Proteins and Diagnosis of Sporadic Creutzfeldt-Jakob Disease in Canada
Michael B. Coulthart,1,† Gerard H. Jansen,2 Elina Olsen,3 Deborah L. Godal,1 Tim Connolly,3 Bernard C. Choi,3 Zheng Wang3 and Neil R. Cashman4
1Public Health Agency of Canada; Winnipeg, MB Canada; 2University of Ottawa; Ottawa, ON Canada; 3Public Health Agency of Canada; Ottawa, ON Canada; 4University of British Columbia; Vancouver, BC Canada†Presenting author; Email: michael.coulthart@phac-aspc.gc.ca
Background. With its range of initial symptoms that may accompany other conditions, and a frequent need for timely diagnosis, sporadic Creutzfeldt-Jakob disease (sCJD) can present the clinician with significant challenges. Particularly widely employed for this purpose are assays for certain brain proteins in cerebrospinal fluid (CSF). Data are needed to better support systematic revision of diagnostic probabilities for sCJD on the basis of CSF protein assay results, in patient populations that also include diverse subacute encephalopathies eliciting a clinical suspicion of sCJD.
Methods. CSF 14-3-3, total Tau and S-100B proteins were studied prospectively in 948 Canadian patients suspected of having sCJD, including 121 with autopsy-confirmed sCJD and 827 with probable non-CJD diagnoses. Various metrics of diagnostic accuracy including sensitivity, specificity, predictive values and likelihood ratios were estimated.
Results. Estimated diagnostic accuracy for individual markers were mostly consistent with those of previously published studies at optimal cutoff thresholds for this study population (empirically defined for 14-3-3 immunoblot; 976 pg/mL for Tau; 2.5 ng/mL for S-100B). Sensitivity and specificity estimates respectively at these thresholds were 0.88 (95% CI, 0.81–0.93) and 0.71 (0.68–0.74) for 14-3-3; 0.90 (0.83–0.95) and 0.87 (0.85–0.90) for Tau; and 0.86 (0.78–0.91) and 0.86 (0.84–0.89) for S-100B; thus, the only outlier was 14-3-3 specificity (~0.7). Positive likelihood ratio (LR+) estimates were low to moderate: 3.0 (2.8–3.3) for 14-3-3; 7.1 (6.6–7.6) for Tau and 6.3 (5.8–6.8) for S-100B at optimal cutoff thresholds. Negative likelihood ratios were moderate: 0.17 (0.10–0.30) for 14-3-3; 0.12 (0.07–0.2) for Tau; and 0.17 (0.10–0.30) for S-100B. Interval LR estimates strengthened accuracy for patient subsets—for example, 31.4% of sCJD patients displayed extreme CSF Tau levels (>12 000 pg/mL), associated with an LR of 64.0 (23.3–175.9). Combining Tau and S-100B results, even at intermediate values, also enhanced accuracy; e.g., LR+ = 55.6 (20.1–153.7) with Tau > 5000 pg/mL and S-100B > 5.0 ng/mL.
Conclusions. CSF Tau and S-100B show comparable or better diagnostic accuracy compared to 14-3-3 in a heterogeneous patient population with low average pre-test probability of sCJD. Tau and S-100B may be optimal choices for many sCJD case investigations. Reporting of quantitative assay results as well as combining Tau and S-100B could enhance the clinical utility of surveillance case definitions for sCJD.
Risk.12: Transmission of Atypical Italian sCJD Case to Humanized Mice Reveals a Novel Infectious Strain
Roberta Galeno,1,† Marco Sbriccoli,1 Loredana Ingrosso,1 Silvia Graziano,1 Angelina Valanzano,1 Anna Poleggi,1 Angela De Pascalis,1 Anna Ladogana,1 Franco Cardone,1 Maria Puopolo,1 Gianluigi Zanusso2 and Maurizio Pocchiari1
1Istituto Superiore di Sanità; Rome, Italy; 2University of Verona; Verona, Italy†Presenting author; Email: roberta.galeno@iss.it
Sporadic Creutzfeldt-Jakob disease (sCJD) is a neurodegenerative prion disorder with uncertain etiology characterized by a typical combination of clinical symptoms, neuropathological lesions, and by the deposition of the pathological protein PrPTSE in the brain.
The vast majority of patients affected by sCJD can be categorized according to the genotype at the polymorphic position
129 of PrP (methionine or valine) and to the molecular mass of PrPTSE (type 1 or 2, corresponding to 21 or 19 kDa), yielding six possible combinations (MM1, MM2, VV1, VV2, MV1, and MV2) that associate with five clinico-pathological variants. Transmission studies of these sCJD subtypes into transgenic mice expressing the human prion protein allowed to identify four different infectious strains, which can partly explain the heterogeneity observed in sCJD patients.1
We recently described a novel molecular and pathological phenotype of sCJD (MV at position 129 of PrP), associated with an unprecedented electrophoretic pattern of PrPTSE characterized by the absence of the highly glycosylated isoform. In this work, we sought to characterize the prion strain associated with this atypical case by intracerebral inoculation into gene-targeted transgenic mice (HuTg) carrying the human PRNP gene with the three 129 genotype combinations. For comparison, three Italian sCJD cases heterozygous at position 129 of the prion protein, belonging to different subtypes (MV1, MV1/2, MV2), were transmitted to the same panel of transgenic mice. Survival times, attack rates, lesion profiles, and molecular analysis of the PrPTSE type recovered from mouse brains injected with the atypical case were compared with data from control animals. Mice inoculated with the atypical case displayed a restricted host tropism, with only a small number of VV animals that resulted PrPTSE-positive after an exceedingly long survival time. Interestingly, PrPTSE accumulated in brains from these mice lacks the diglycosylated band similar to that in sCJD inoculum, yet dissimilar to any other PrPTSE observed in HuTg mice by us and by other authors.1,2 Overall, these results strongly indicate that our atypical case associates with a new infectious strain of sCJD. Further investigations are needed to understand the possible connection with other human and animal prion diseases.
References
1. Bishop MT, Will RG, Manson JC. Defining sporadic Creutzfeldt-Jakob disease strains and their transmission properties. Proc Natl Acad Sci USA 2010; 107:12005-10.
2. Bishop MT, Hart P, Aitchison L, Baybutt HN, Plinston C, Thomson V, et al. Predicting susceptibility and incubation time of human-to-human transmission of vCJD. Lancet Neurol 2006; 5:393-8.
Risk.21: Thirty-Year Review of Prion Disease Surveillance in the United States
Robert C. Holman,1,† Ryan A. Maddox,1 Arianne M. Folkema,1 Arialdi M. Minino,2 Teresa A. Hammett,1 Kenneth D. Kochanek,2 James J. Sejvar,1 Ermias D. Belay1 and Lawrence B. Schonberger,1
1CDC; Atlanta, GA USA; 2CDC; Hyattsville, MD USA†Presenting author; Email: rholman@cdc.gov
Background. With the emergence of bovine spongiform encephalopathy/variant Creutzfeldt-Jakob disease (vCJD) in the UK, the Centers for Disease Control and Prevention began utilizing national mortality data with additional surveillance mechanisms to monitor US occurrences of human prion disease.
Objectives. To review US prion disease surveillance data.
Methods. We analyzed national mortality data for prion disease deaths (a surrogate for CJD incidence) among US residents for the 30 year period, 1979–2008, augmenting and extending these data through 2010 with information from other surveillance mechanisms (e.g., national neuropathology surveillance). We calculated age-adjusted and age-specific death rates per million persons; race-specific rates used data available beginning 1981. We age-adjusted death rates to the standard projected US 2000 population. www.landesbioscience.com Prion 131
Results. A total of 7,615 deaths during 1979–2008 were identified for an average annual age-adjusted rate of 0.98 cases per million persons. The highest rate (1.15) was observed in 1997; the highest number of reported cases was in 2008 (348). By race, the rate (1.06) among whites, who constituted 95% of the cases, was significantly higher than among blacks (0.40), Asian/Pacific Islanders (0.63) and American Indians/Alaska Natives (0.42). The rate (4.0) among persons =55 years old was strikingly higher than the rate (0.14) among persons <55 years old. The youngest decedent was age 21 years. None of the deaths during the 30 year period were reported with hereditary factor VIII or IX deficiency, thalassemia, or sickle cell disease. Through 2010, the only identified vCJD decedents among US residents were the three in 2004-2006 who were previously reported as likely infected in the UK or Saudi Arabia.
Conclusion. The annual age-adjusted US CJD death rates remained relatively stable over several decades although the most recent, complete, annual data show the highest number of cases. The absence of CJD in persons <20 years of age despite an estimated magnitude of 100,000 transfusion recipients <5 years of age who remained at risk during the surveillance period plus many times more such youngsters who received blood products and the absence of CJD in persons with hemophilia (current population ~20,000), thalassemia (~1,000) or sickle cell disease (~100,000) suggests the risk, if any, of blood-related CJD transmissions is likely very low. Racial differences in CJD rates deserve further investigation.
Risk.27: Creutzfeldt-Jakob Disease Among Hispanics in the United States, 1997–2008
Ryan A. Maddox,1,† Robert C. Holman,1 Arianne M. Folkema,1 Arialdi M. Minino,2 Teresa A. Hammett,1 Lawrence B. Schonberger1 and Ermias D. Belay1
1National Center for Zoonotic and Emerging Infectious Diseases; Centers for Disease Control and Prevention; Atlanta, GA USA; 2National Center for Health Statistics; Centers for Disease Control and Prevention; Hyattsville, MD USA†Presenting author; Email: rmaddox@cdc.gov
Introduction. At 16% of the US population, Hispanics make up the largest ethnic or racial minority in the country, and this proportion is expected to increase in the coming decades. The occurrence of Creutzfeldt-Jakob disease (CJD) among Americans of Hispanic ethnicity has not been widely investigated.
Methods. Hispanic CJD decedents of any age were identified from the US national multiple cause-of-death data and other sources for 1997–2008. Relevant portions of medical records and results from neuropathologic and genetic testing for Hispanic CJD decedents <55 years of age were obtained and reviewed, as available.
Results. During 1997–2008, 160 CJD decedents were identified as being of Hispanic ethnicity, for an average annual age-adjusted incidence of 0.65 per million population, an incidence significantly lower than that for non-Hispanics (RR =0.6; 95% CI 0.5–0.7). While 27 states reported at least one Hispanic decedent during the time period, almost half (47.5%) of the decedents were residents of California or Texas, the states with the highest Hispanic populations. A majority (55.0%) of the decedents were females, but the average annual age-adjusted incidence was slightly higher for males, although the difference was not significant. The median age at death was 64 years (range 36-93 years). Thirty-three Hispanic CJD decedents (20.6%) were <55 years of age, compared to 12.1% of cases in that age group among non-Hispanic CJD decedents; however, the average annual age-specific incidence for CJD decedents <55 years of age was significantly lower among Hispanics compared to non-Hispanics (0.08 compared to 0.17, respectively; p < 0.0001). Of the 33 young Hispanic CJD decedents, 21 (63.6%) had medical records and/or neuropathology reports available for review. Ten of these 21 cases (47.6%) had neuropathologic confirmation, including three decedents with familial CJD and one decedent with sporadic fatal insomnia.
Conclusions. Between 1997 and 2008, the reported CJD incidence among Hispanics in the US was significantly lower than that for non-Hispanics. This lower incidence may be at least partly due to underreporting of Hispanic ethnicity relative to surveys and censuses, and further study is warranted. Analyses of brain tissue remain important, especially considering that approximately half of the young Hispanic decedents with information available lacked CJD confirmation.
Risk.26: Sex Effect in Prion Diseases
Corinne Loeillet,1,† Pierre-Yves Boelle,2 Catherine Lemaire-Vieille,1 Philippe Naquet,3 Pierre Chambon,4 Marie-France Cesbron-Delauw,1 Alain-Jacques Valleron,2 Jean Gagnon1 and Jean-Yves Cesbron1
1CNRS LAPM 5163–Université Joseph Fourier; Grenoble, France; 2INSERM U 707–2 Université Pierre et Marie Curie–Paris 6; Paris, France; 3Centre d’Immunologie de Marseille-Luminy, INSERM-CNRS; Marseille, France; 4Institut de Génétique et de Biologie Moléculaire et Cellulaire, Université Louis Pasteur de Strasbourg; Strasbourg, France†Presenting author; Email: corinne.loeuillet@ujf-grenoble.fr
Despite large exposure to BSE in the UK, less than 180 patients had developed clinical vCJD by October 2009. This figure was closely anticipated in 2001, thanks to an epidemiological model whose main assumptions was that the risk of acquiring vCJD was exponentially decreasing during childhood, which was consistent with the age distribution of vCJD. Further investigation of the models showed that this decrease of risk during childhood could not be explained by the age variation of meat consumption, and was likely a consequence of an age dependent susceptibility to the disease. The more likely explanation for this strong age-susceptibility relationship during childhood is hormonal.
In this context, we investigated if there was a sex difference in human vCJD cases, and we used a mouse model to test a first hypothesis on the possible role of sexual hormones on the risk of prion diseases.
In the 167 vCJD cases reported in the UK as of January 2009, age at onset was significantly lower in women (two years) than in men after stratification on birth cohort. In C57/BL6N mice infected with ME-7 scrapie strain, incubation was shorter in females than in males. The incubation period increased in castrated male mice after intraperitoneal infection, but not after intracerebral inoculation. We also observed that androgen receptor deficient mice the incubation period of prion disease also increased after intraperitoneal inoculation. In contrast, in ovariectomised or estrogen receptor a defective female mice, no effect was observed on the incubation period of mouse prion disease.
These results show that androgens influence the prion diseases incubation period in a peripheral site.1
References
1. Loeuillet C, Boelle PY, Lemaire-Vieille C, Baldazza M, Naquet P, Chambon P, et al. Sex effect in mouse and human prion disease. J Infect Dis 2010; 202:648-54.
Risk.49: Creutzfeldt-Jakob Disease in Canada, 1998–2009
Zheng Wang,1,† Gerard Jansen,1, 2 Elina Olsen,1 Stacy Sabourin,1 Rolande D’Amour,1 Tim Connolly,1 Jennifer Kruse,1 Neil Cashman3 and Michael Coulthart1
1The Canadian Creutzfeldt-Jakob Disease Surveillance System; Public Health Agency of Canada; Ottawa, ON Canada; 2Department of Pathology; Ottawa Hospital; Ottawa, ON Canada; 3Brain Research Centre; University of British Columbia; Vancouver, BC Canada†Presenting author; Email: zheng.wang@phac-aspc.gc.ca
Background. Creutzfeldt-Jakob Disease (CJD) is a fatal, transmissible neurodegenerative disease with sporadic, genetic and acquired forms. In 1998, Canada launched comprehensive national CJD surveillance to assess the characteristics of CJD in Canada and its risks to the health of Canadians. This study describes the broad characteristics of CJD in Canada from 1998–2009.
Methods. Case ascertainment was based on internationally accepted criteria. Demographic information and risk-factor data were collected by standardized questionnaire and medical chart review. Poisson regression, descriptive analysis, and case investigation were employed.
Results. A total of 453 CJD deaths in Canadian residents were registered from 1998–2009. Four hundred and fifteen (92%) were sporadic (sCJD), 33 (7%) were genetic and five (1%) were acquired. Average annual sCJD mortality was 1.1 per million population, increasing gradually from 0.9 in 1999 to 1.4 in 2009 (P = 0.27). All provinces saw average annual mortalities ranging from 1.0 to 1.5 (P = 0.85), except three territories where population is small (~25,000 to ~45,000), sCJD occurred equally in both genders at 1.1. sCJD was rare under 50 years of age with only 11 cases identified (2.7%). Mortality increased after 50 and peaked at 8 per million in the 70–74 age group. Median age at death was 69 and median duration of illness was 4 months. Genetic TSE accounted for 33 deaths: 19 were GSS (P102L: 5, D202N: 2, P105T: 2, Q217R:1, A117V: 1, unknown mutation: 8); 13 were familial CJD (E200K: 9, D178N: 2, V203I: 1, V189I:1); one was FFI (D178N). Median age for genetic TSE was 59 and median duration of illness was 27 months. For the five acquired cases of CJD, four were associated with dura mater procedures (3 Lyodura, 1 Tutoplast) and were identified from 1998–2003 in patients aged 14–59. Investigation indicated the infections possibly occurred from 1981–1992 with incubation times from 10–16 years. One biochemically and neuropathologically confirmed variant CJD death occurred in 2002 in a person under 40 years old, likely acquired overseas.
Discussion and Conclusion. Characteristics of CJD in Canada are consistent with those observed in other countries. The increase in sCJD mortality can be at least partly attributed to increased awareness of CJD among referring clinicians. The finding of four dura matter associated CJD cases and one imported vCJD case in Canada demonstrate risks to Canadians from acquired CJD exist. Continued surveillance for iatrogenic risks and novel forms of CJD is warranted.
Risk.50: Investigating Dental Treatment as a Possible Risk Factor for Variant Creutzfeldt-Jakob Disease (vCJD) in the UK
Dawn Everington,1 Andrew Smith,2 Pauline Watt,1 Fiona Ord,1 Anna Molesworth,1 Robert Will1,† and Hester Ward1
1National CJD Surveillance Unit; Edinburgh, UK; 2College of Medical, Veterinary and Life Sciences; University of Glasgow; Glasgow, UK;†Presenting author; Email: r.g.will@ed.ac.uk
Introduction. The potential for vCJD transmission in the healthcare setting has raised concerns over the risk posed by dental surgery. The aim of this study was to determine whether dental treatment was a possible risk factor for vCJD.
Methods. Dental treatment records were collected from general dental practitioners or, where this was not possible, from NHS Dental Practice Board payment schedules. We looked for links between vCJD cases and whether there was an excess of dental treatment in vCJD cases compared with general population controls.
Results. Data were available for 49% (79/162) of cases and 82% (503/610) of controls. Two pairs of cases had attended the same dental practice, multiple treatment data were traced for one pair. While theoretically possible that the same instruments could have been used on both cases, after considering the type and timing of interventions we propose that the probability of cross-infection is very small. The review of specific dental treatments showed that there was no evidence that vCJD cases experienced an excess of any type of dental treatment compared with controls.
Conclusions. This study provided no compelling evidence of a strong association between dental treatment and vCJD, however because of the limited availability of dental information, and the possibility of undetected asymptomatic infection, we cannot exclude dental treatment as a possible risk factor for vCJD. We support current health policy to ensure that high standards of cleaning and sterilization of re-usable dental instruments are maintained.
http://www.prion2011.ca/files/PRION_2011_-_Posters_(May_5-11).pdf
CANADA CJD UPDATE 2011
CJD Deaths Reported by CJDSS1, 1994-20112 As of January 31, 2011
3. Final classification of 49 cases from 2009, 2010, 2011 is pending.
snip...
http://www.phac-aspc.gc.ca/hcai-iamss/cjd-mcj/cjdss-ssmcj/pdf/stats_0111-eng.pdf
USA 2011
USA
National Prion Disease Pathology Surveillance Center
Cases Examined1
(November 1, 2010)
Year Total Referrals2 Prion Disease Sporadic Familial Iatrogenic vCJD
1996 & earlier 51 33 28 5 0 0
1997 114 68 59 9 0 0
1998 87 51 43 7 1 0
1999 121 73 65 8 0 0
2000 146 103 89 14 0 0
2001 209 119 109 10 0 0
2002 248 149 125 22 2 0
2003 274 176 137 39 0 0
2004 325 186 164 21 0 13
2005 344 194 157 36 1 0
2006 383 197 166 29 0 24
2007 377 214 187 27 0 0
2008 394 231 205 25 0 0
2009 425 258 215 43 0 0
2010 333 213 158 33 0 0
TOTAL 38315 22656 1907 328 4 3
1 Listed based on the year of death or, if not available, on year of referral;
2 Cases with suspected prion disease for which brain tissue and/or blood (in familial cases) were submitted;
3 Disease acquired in the United Kingdom;
4 Disease was acquired in the United Kingdom in one case and in Saudi Arabia in the other case;
5 Includes 18 cases in which the diagnosis is pending, and 18 inconclusive cases;
6 Includes 23 (22 from 2010) cases with type determination pending in which the diagnosis of vCJD has been excluded.
http://www.cjdsurveillance.com/pdf/case-table.pdf
Please notice where sporadic CJD cases in 1996 went from 28 cases, to 215 cases in 2009, the highest recorded year to date. sporadic CJD is on a steady rise, and has been since 1996.
I also urge you to again notice these disturbing factors in lines 5 and 6 ;
5 Includes 18 cases in which the diagnosis is pending, and 18 inconclusive cases;
6 Includes 23 (22 from 2010) cases with type determination pending in which the diagnosis of vCJD has been excluded.
========end=====tss=====2011
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
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
Thursday, August 4, 2011
Terry Singeltary Sr. on the Creutzfeldt-Jakob Disease Public Health Crisis, Date aired: 27 Jun 2011
see video here ;
http://transmissiblespongiformencephalopathy.blogspot.com/2011/08/terry-singeltary-sr-on-creutzfeldt.html
Saturday, January 2, 2010
Human Prion Diseases in the United States January 1, 2010 ***FINAL***
http://prionunitusaupdate2008.blogspot.com/2010/01/human-prion-diseases-in-united-states.html
Manuscript Draft Manuscript Number: Title: HUMAN and ANIMAL TSE Classifications i.e. mad cow disease and the UKBSEnvCJD only theory Article Type: Personal View Corresponding Author: Mr. Terry S. Singeltary, Corresponding Author's Institution: na First Author: Terry S Singeltary, none Order of Authors: Terry S Singeltary, none; Terry S. Singeltary Abstract: TSEs have been rampant in the USA for decades in many species, and they all have been rendered and fed back to animals for human/animal consumption. I propose that the current diagnostic criteria for human TSEs only enhances and helps the spreading of human TSE from the continued belief of the UKBSEnvCJD only theory in 2007.
http://www.regulations.gov/fdmspublic/ContentViewer?objectId=090000648027c28e&disposition=attachment&contentType=pdf
my comments to PLosone here ;
http://www.plosone.org/annotation/listThread.action?inReplyTo=info%3Adoi%2F10.1371%2Fannotation%2F04ce2b24-613d-46e6-9802-4131e2bfa6fd&root=info%3Adoi%2F10.1371%2Fannotation%2F04ce2b24-613d-46e6-9802-4131e2bfa6fd
Sunday, August 09, 2009
CJD...Straight talk with...James Ironside...and...Terry Singeltary... 2009
http://creutzfeldt-jakob-disease.blogspot.com/2009/08/cjdstraight-talk-withjames.html
Tuesday, August 18, 2009
BSE-The Untold Story - joe gibbs and singeltary 1999 - 2009
http://madcowusda.blogspot.com/2009/08/bse-untold-story-joe-gibbs-and.html
Friday, February 11, 2011
Creutzfeldt-Jakob disease (CJD) biannual update (2010/1) Emerging infections/CJD
http://creutzfeldt-jakob-disease.blogspot.com/2011/02/creutzfeldt-jakob-disease-cjd-biannual.html
Friday, April 15, 2011
PRION TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY PROJECTS, RESEARCH FUNDING, BSE VOLUNTARY TESTING UPDATE IN NORTH AMERICA 2011
http://prionunitusaupdate2008.blogspot.com/2011/04/prion-transmissible-spongiform.html
PRION TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY RESEARCH FUNDING U.S.A.
COMPARE TO USA PRION FUNDING 2011
"which includes the ___elimination___ of Prion activities ($5,473,000),"
All Other Emerging and Zoonotic Infectious Diseases CDC‘s FY 2012 request of $52,658,000 for all other emerging and zoonotic infectious disease activities is a decrease of $13,607,000 below the FY 2010 level, which includes the elimination of Prion activities ($5,473,000), a reduction for other cross-cutting infectious disease activities, and administrative savings. These funds support a range of critical emerging and zoonotic infectious disease programs such Lyme Disease, Chronic Fatigue Syndrome, and Special Pathogens, as well as other activities described below.
http://www.cdc.gov/fmo/topic/Budget%20Information/appropriations_budget_form_pdf/FY2012_CDC_CJ_Final.pdf
THE PATHOLOGICAL PROTEIN
BY Philip Yam
Yam Philip Yam News Editor Scientific American www.sciam.com
Answering critics like Terry Singeltary, who feels that the U.S. under- counts CJD, Schonberger conceded that the current surveillance system has errors but stated that most of the errors will be confined to the older population.
CHAPTER 14
Laying Odds
Are prion diseases more prevalent than we thought?
Researchers and government officials badly underestimated the threat that mad cow disease posed when it first appeared in Britain. They didn't think bovine spongiform encephalopathy was a zoonosis-an animal disease that can sicken people. The 1996 news that BSE could infect humans with a new form of Creutzfeldt-Jakob disease stunned the world. It also got some biomedical researchers wondering whether sporadic CJD may really be a manifestation of a zoonotic sickness. Might it be caused by the ingestion of prions, as variant CJD is?
Revisiting Sporadic CJD
It's not hard to get Terry Singeltary going. "I have my conspiracy theories," admitted the 49-year-old Texan.1 Singeltary is probably the nation's most relentless consumer advocate when it comes to issues in prion diseases. He has helped families learn about the sickness and coordinated efforts with support groups such as CJD Voice and the CJD Foundation. He has also connected with others who are critical of the American way of handling the threat of prion diseases. Such critics include Consumers Union's Michael Hansen, journalist John Stauber, and Thomas Pringle, who used to run the voluminous www.madcow. org Web site. These three lend their expertise to newspaper and magazine stories about prion diseases, and they usually argue that prions represent more of a threat than people realize, and that the government has responded poorly to the dangers because it is more concerned about protecting the beef industry than people's health.
Singeltary has similar inclinations. ...
snip...
THE PATHOLOGICAL PROTEIN
Hardcover, 304 pages plus photos and illustrations. ISBN 0-387-95508-9
June 2003
BY Philip Yam
CHAPTER 14 LAYING ODDS
Answering critics like Terry Singeltary, who feels that the U.S. under- counts CJD, Schonberger conceded that the current surveillance system has errors but stated that most of the errors will be confined to the older population.
http://www.thepathologicalprotein.com/
http://books.google.com/books?id=ePbrQNFrHtoC&pg=PA223&lpg=PA223&dq=the+pathological+protein+laying+odds+It%E2%80%99s+not+hard+to+get+Terry+Singeltary+going&source=bl&ots=um0PFAZSZD&sig=JWaGR7M7-1WeAr2qAXq8D6J_jak&hl=en&ei=MhtjS8jMJM2ztgeFoa2iBg&sa=X&oi=book_result&ct=result&resnum=1&ved=0CAcQ6AEwAA#v=onepage&q=&f=false
http://www.springerlink.com/content/r2k2622661473336/fulltext.pdf?page=1
http://www.thepathologicalprotein.com/
http://prionunitusaupdate2008.blogspot.com/2009/04/national-prion-disease-pathology.html
Newsdesk The Lancet Infectious Diseases, Volume 3, Issue 8, Page 463, August 2003 doi:10.1016/S1473-3099(03)00715-1Cite or Link Using DOI
Tracking spongiform encephalopathies in North America
Xavier Bosch
"My name is Terry S Singeltary Sr, and I live in Bacliff, Texas. I lost my mom to hvCJD (Heidenhain variant CJD) and have been searching for answers ever since. What I have found is that we have not been told the truth. CWD in deer and elk is a small portion of a much bigger problem." 49-year-old Singeltary is one of a number of people who have remained largely unsatisfied after being told that a close relative died from a rapidly progressive dementia compatible with spontaneous Creutzfeldt-Jakob disease (CJD). So he decided to gather hundreds of documents on transmissible spongiform encephalopathies (TSE) and realised that if Britons could get variant CJD from bovine spongiform encephalopathy (BSE), Americans might get a similar disorder from chronic wasting disease (CWD)-the relative of mad cow disease seen among deer and elk in the USA. Although his feverish.
http://linkinghub.elsevier.com/retrieve/pii/S1473309903007151
http://www.thelancet.com/journals/laninf/article/PIIS1473-3099(03)00715-1/fulltext
http://www.mdconsult.com/das/article/body/180784492-2/jorg=journal&source=&sp=13979213&sid=0/N/368742/1.html?issn=14733099
Diagnosis and Reporting of Creutzfeldt-Jakob Disease Singeltary, Sr et al. JAMA.2001; 285: 733-734. Vol. 285 No. 6, February 14, 2001 JAMA
Diagnosis and Reporting of Creutzfeldt-Jakob Disease
To the Editor: In their Research Letter, Dr Gibbons and colleagues1 reported that the annual US death rate due to Creutzfeldt-Jakob disease (CJD) has been stable since 1985. These estimates, however, are based only on reported cases, and do not include misdiagnosed or preclinical cases. It seems to me that misdiagnosis alone would drastically change these figures. An unknown number of persons with a diagnosis of Alzheimer disease in fact may have CJD, although only a small number of these patients receive the postmortem examination necessary to make this diagnosis. Furthermore, only a few states have made CJD reportable. Human and animal transmissible spongiform encephalopathies should be reportable nationwide and internationally.
Terry S. Singeltary, Sr Bacliff, Tex
1. Gibbons RV, Holman RC, Belay ED, Schonberger LB. Creutzfeldt-Jakob disease in the United States: 1979-1998. JAMA. 2000;284:2322-2323. FREE FULL TEXT
http://jama.ama-assn.org/cgi/content/extract/285/6/733?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=singeltary&searchid=1&FIRSTINDEX=0&resourcetype=HWCIT
http://jama.ama-assn.org/cgi/content/full/285/6/733?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=singeltary&searchid=1&FIRSTINDEX=0&resourcetype=HWCIT
DER SPIEGEL (9/2001) - 24.02.2001 (9397 Zeichen) USA: Loch in der Mauer Die BSE-Angst erreicht Amerika: Trotz strikter Auflagen gelangte in Texas verbotenes Tiermehl ins Rinderfutter - die Kontrollen der Aufsichtsbehördensind lax.Link auf diesen Artikel im Archiv:
http://service.spiegel.de/digas/find?DID=18578755
"Löcher wie in einem Schweizer Käse" hat auch Terry Singeltary im Regelwerk der FDA ausgemacht. Der Texaner kam auf einem tragischen Umweg zu dem Thema: Nachdem seine Mutter 1997 binnen weniger Wochen an der Creutzfeldt-Jakob-Krankheit gestorben war, versuchte er, die Ursachen der Infektion aufzuspüren. Er klagte auf die Herausgabe von Regierungsdokumenten und arbeitete sich durch Fachliteratur; heute ist er überzeugt, dass seine Mutter durch die stetige Einnahme von angeblich kräftigenden Mitteln erkrankte, in denen - völlig legal - Anteile aus Rinderprodukten enthalten sind.
Von der Fachwelt wurde Singeltary lange als versponnener Außenseiter belächelt. Doch mittlerweile sorgen sich auch Experten, dass ausgerechnet diese verschreibungsfreien Wundercocktails zur Stärkung von Intelligenz, Immunsystem oder Libido von den Importbeschränkungen ausgenommen sind. Dabei enthalten die Pillen und Ampullen, die in Supermärkten verkauft werden, exotische Mixturen aus Rinderaugen; dazu Extrakte von Hypophyse oder Kälberföten, Prostata, Lymphknoten und gefriergetrocknetem Schweinemagen. In die USA hereingelassen werden auch Blut, Fett, Gelatine und Samen. Diese Stoffe tauchen noch immer in US-Produkten auf, inklusive Medizin und Kosmetika. Selbst in Impfstoffen waren möglicherweise gefährliche Rinderprodukte enthalten. Zwar fordert die FDA schon seit acht Jahren die US-Pharmaindustrie auf, keine Stoffe aus Ländern zu benutzen, in denen die Gefahr einer BSE-Infizierung besteht. Aber erst kürzlich verpflichteten sich fünf Unternehmen, darunter Branchenführer wie GlaxoSmithKline, Aventis und American Home Products, ihre Seren nur noch aus unverdächtigem Material herzustellen.
"Its as full of holes as Swiss Cheese" says Terry Singeltary of the FDA regulations. ...
http://www.spiegel.de/spiegel/print/d-18578755.html
http://wissen.spiegel.de/wissen/image/show.html?did=18578755&aref=image024/E0108/SCSP200100901440145.pdf&thumb=false
http://service.spiegel.de/digas/servlet/find/DID=18578755
Suspect symptoms
What if you can catch old-fashioned CJD by eating meat from a sheep infected with scrapie?
28 Mar 01
Like lambs to the slaughter 31 March 2001 by Debora MacKenzie Magazine issue 2284. Subscribe and get 4 free issues. FOUR years ago, Terry Singeltary watched his mother die horribly from a degenerative brain disease. Doctors told him it was Alzheimer's, but Singeltary was suspicious. The diagnosis didn't fit her violent symptoms, and he demanded an autopsy. It showed she had died of sporadic Creutzfeldt-Jakob disease.
Most doctors believe that sCJD is caused by a prion protein deforming by chance into a killer. But Singeltary thinks otherwise. He is one of a number of campaigners who say that some sCJD, like the variant CJD related to BSE, is caused by eating meat from infected animals. Their suspicions have focused on sheep carrying scrapie, a BSE-like disease that is widespread in flocks across Europe and North America.
Now scientists in France have stumbled across new evidence that adds weight to the campaigners' fears. To their complete surprise, the researchers found that one strain of scrapie causes the same brain damage in mice as sCJD.
"This means we cannot rule out that at least some sCJD may be caused by some strains of scrapie," says team member Jean-Philippe Deslys of the French Atomic Energy Commission's medical research laboratory in Fontenay-aux-Roses, south-west of Paris. Hans Kretschmar of the University of Göttingen, who coordinates CJD surveillance in Germany, is so concerned by the findings that he now wants to trawl back through past sCJD cases to see if any might have been caused by eating infected mutton or lamb.
Scrapie has been around for centuries and until now there has been no evidence that it poses a risk to human health. But if the French finding means that scrapie can cause sCJD in people, countries around the world may have overlooked a CJD crisis to rival that caused by BSE.
Deslys and colleagues were originally studying vCJD, not sCJD. They injected the brains of macaque monkeys with brain from BSE cattle, and from French and British vCJD patients. The brain damage and clinical symptoms in the monkeys were the same for all three. Mice injected with the original sets of brain tissue or with infected monkey brain also developed the same symptoms.
As a control experiment, the team also injected mice with brain tissue from people and animals with other prion diseases: a French case of sCJD; a French patient who caught sCJD from human-derived growth hormone; sheep with a French strain of scrapie; and mice carrying a prion derived from an American scrapie strain. As expected, they all affected the brain in a different way from BSE and vCJD. But while the American strain of scrapie caused different damage from sCJD, the French strain produced exactly the same pathology.
"The main evidence that scrapie does not affect humans has been epidemiology," says Moira Bruce of the neuropathogenesis unit of the Institute for Animal Health in Edinburgh, who was a member of the same team as Deslys. "You see about the same incidence of the disease everywhere, whether or not there are many sheep, and in countries such as New Zealand with no scrapie." In the only previous comparisons of sCJD and scrapie in mice, Bruce found they were dissimilar.
But there are more than 20 strains of scrapie, and six of sCJD. "You would not necessarily see a relationship between the two with epidemiology if only some strains affect only some people," says Deslys. Bruce is cautious about the mouse results, but agrees they require further investigation. Other trials of scrapie and sCJD in mice, she says, are in progress.
People can have three different genetic variations of the human prion protein, and each type of protein can fold up two different ways. Kretschmar has found that these six combinations correspond to six clinical types of sCJD: each type of normal prion produces a particular pathology when it spontaneously deforms to produce sCJD.
But if these proteins deform because of infection with a disease-causing prion, the relationship between pathology and prion type should be different, as it is in vCJD. "If we look at brain samples from sporadic CJD cases and find some that do not fit the pattern," says Kretschmar, "that could mean they were caused by infection."
There are 250 deaths per year from sCJD in the US, and a similar incidence elsewhere. Singeltary and other US activists think that some of these people died after eating contaminated meat or "nutritional" pills containing dried animal brain. Governments will have a hard time facing activists like Singeltary if it turns out that some sCJD isn't as spontaneous as doctors have insisted.
Deslys's work on macaques also provides further proof that the human disease vCJD is caused by BSE. And the experiments showed that vCJD is much more virulent to primates than BSE, even when injected into the bloodstream rather than the brain. This, says Deslys, means that there is an even bigger risk than we thought that vCJD can be passed from one patient to another through contaminated blood transfusions and surgical instruments.
http://www.newscientist.com/article/mg16922840.300-like-lambs-to-the-slaughter.html
2 January 2000
British Medical Journal
U.S. Scientist should be concerned with a CJD epidemic in the U.S., as well
http://www.bmj.com/cgi/eletters/320/7226/8/b#6117
15 November 1999
British Medical Journal
vCJD in the USA * BSE in U.S.
http://www.bmj.com/cgi/eletters/319/7220/1312/b#5406
2006
USA sporadic CJD cases rising ;
There is a growing number of human CJD cases, and they were presented last week in San Francisco by Luigi Gambatti(?) from his CJD surveillance collection.
He estimates that it may be up to 14 or 15 persons which display selectively SPRPSC and practically no detected RPRPSC proteins.
http://www.fda.gov/ohrms/dockets/ac/06/transcripts/1006-4240t1.htm
http://www.fda.gov/ohrms/dockets/ac/06/transcripts/2006-4240t1.pdf
Thursday, July 08, 2010
GLOBAL CLUSTERS OF CREUTZFELDT JAKOB DISEASE - A REVIEW 2010
http://creutzfeldt-jakob-disease.blogspot.com/2010/07/global-clusters-of-creutzfeldt-jakob.html
Wednesday, June 29, 2011
TSEAC Meeting August 1, 2011 donor deferral vCJD...
http://tseac.blogspot.com/2011/06/tseac-meeting-august-1-2011-donor.html
TSS
(CJD...see old video here from EU)
see new url here ;
http://zoomify.uzh.ch:8080/zoomify/videos/video-009/video-009.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
Sunday, August 21, 2011
Classical Bovine Spongiform Encephalopathy by Transmission of H-Type Prion in Homologous Prion Protein Context
Volume 17, Number 9–September 2011
Research
http://transmissiblespongiformencephalopathy.blogspot.com/2011/08/classical-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
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
Risk.16: Clinical Disease in Cattle Experimentally Inoculated with All Types of BSE
Catherine Graham,1,† Michel Levy,2 Ed Pajor,2 Garth McGregor,1 Rheana Flitton1 and Stefanie Czub1
1Canadian Food Inspection Agency; Lethbridge, AB Canada; 2Faculty of Veterinary Medicine; University of Calgary; Calgary, AB Canada†Presenting author; Email: catherine.graham@inspection.gc.ca
Background. Classical, or C-type, bovine spongiform encephalopathy (BSE) has been extensively described in the literature. Recently, two novel forms of BSE, termed atypical BSE, have been reported in a number of countries. These new forms show differences in the biochemical characteristics of the prion protein and, where reported, tend to occur in aged animals but descriptions of clinical presentation are incomplete or absent.
Materials and Methods. Female Hereford/Angus cross calves were intracranially challenged at approximately five months of age with 1 ml of a 10% brain homogenate originating from Canadian field cases of BSE which had been previously classified as C-, L-, or H- type.
The animals were monitored during incubation period, and clinical disease is described using a standardized examination protocol. Incubation period, description and progression of clinical signs was recorded and videotaped for objective evaluation.
Results. All L- and H- type atypical BSE challenged animals began to display signs of clinical disease at approximately 11 months post inoculation, and disease progression was slow but constant until animals were euthanized. Clinical signs in all atypical BSE inoculated animals included hesitation at doors and gates, spontaneous muscle fasciculations and sensitivity to touch. Teeth grinding and excessive salivation are occasionally noted. Animals with L-type BSE are very anxious and show high levels of sensitivity to hand movement. One H-type animal shows periods of somnolence. Both H-type inoculated animals go down during handling and have difficulty rising and show sensitivity to movement around their head and neck area, but to a lesser degree than the L-type BSE inoculated animals. Interestingly, no locomotor abnormalities have been observed in either group.
C-type challenged animals remain normal at approximately 18 months post inoculation. Clinical disease in C-type inoculated animals from a previous transmission study was typically slow and intermittently displayed during the initial stages and after a period of two to four months was more consistent and progressive. Clinical signs in C-type BSE were as previously reported in the literature.
Discussion. The spectrum of clinical signs for all three types of BSE examined is similar. Incubation period is shorter for H- and L-type BSE as compared with C-type. Once clinical signs begin, progression is slow but relentless in atypical BSE, and more insidious in classical BSE. A summary of clinical signs presented in the three different types of BSE will be presented, and video of clinical disease will be displayed.
http://www.prion2011.ca/files/PRION_2011_-_Posters_(May_5-11).pdf
Risk.04: Demographic and Diagnostic Differences in Minorities with Sporadic Creutzfeldt-Jakob Disease
Brian S. Appleby,1,† Kristin K. Appleby2, 3 and Mitchell T. Wallin2
1Johns Hopkins University School of Medicine; Baltimore, MD USA; 2Veterans Affairs Medical Center; Washington, DC USA; 3Parkinson’s and Movement Disorders Center of Maryland; Elkridge, MD USA†Presenting author; Email: bappleb1@jhmi.edu
Sporadic Creutzfeldt-Jakob disease (sCJD) is the most common form of human prion disease. Prior epidemiologic studies of CJD in the U.S.A have reported a lower age adjusted incidence rate for blacks compared to whites. The goal of this study was to explore possible demographic and diagnostic features that could explain this finding.
Method. Previously collected data from Johns Hopkins and the Veterans Affairs Health Care System (VHS) between 1995-2007 were analyzed in this study following IRB approval. Only probable and definite cases of sCJD were included in the final analyses. Caucasian and Hispanic subjects were characterized as white and all other ethnicities were considered non-white in analyses. Chi-square analyses were used for categorical variables and Kaplan-Meier analyses were used for continuous variables.
Results. 116 subjects [n = 100 (86.2%) Caucasian, n = 6 (5.2%) black, n = 6 (5.2%) Hispanic, and n = 4 (3.4%) other race] were included in this study. Age at disease onset differed significantly between whites (mean = 65.2 ± 0.89 years) and non-whites (mean = 57.8 ± 2.94 years) (Log Rank = 5.32, p = 0.021). The correct clinical diagnosis was determined more rapidly in non-whites (46.7 ± 19.5 days) compared to whites (197.3 ± 35.6 days) (Log Rank = 7.08, p = 0.008). Although tissue diagnosis did not differ significantly between groups, non-whites were less likely to undergo autopsy (1/10, 10%) compared to whites (51/103, 49.5%) (Fisher’s exact test, 2-sided, p = 0.02).
Conclusions. In this study population, non-whites had an earlier age at disease onset compared to whites. Non-whites also received the correct clinical diagnosis more quickly compared to whites and were less likely to undergo autopsy. Given these results, it is unclear if non-whites truly have a younger age at onset compared to whites as this may be the result of ascertainment bias. The much more rapid clinical diagnosis of non-whites suggests that a diagnosis of CJD was considered earlier in non-whites who had an earlier age at disease onset. The decreased autopsy rate of non-whites is also concerning as this may falsely lower the estimated incidence of sCJD in non-whites in epidemiologic studies that rely heavily on neuropathologic data. Further studies examining the incidence and diagnostic process of sCJD in non-whites is needed. This study also demonstrates the importance of including patients that are diagnosed clinically and who do not undergo autopsies in CJD surveillance efforts.
Risk.06: Could National Mortality Registers Provide Reliable Indicators for Creutzfeldt-Jakob Disease Surveillance? A Study in France from the 2000-2008 Mortality Data
Jean-Philippe Brandel,1, 5, 7,† Arlette Welaratne,1 Dominique Salomon,2, 7 Isabelle Capek,3 Véronique Vaillant,3 Albertine Aouba,4 Stéphane Haïk5, 7, 1 and Annick Alpérovitch2, 8
1APHP Groupe Hospitalier Pitié Salpêtrière; Paris, France; 2INSERM U708 Neuroepidemiology; Paris, France; 3Institut de Veille Sanitaire; Saint Maurice, France; 4INSERM CépiDc; Le Vésinet, France; 5INSERM UMR-S 975 Equipe maladie d’Alzheimer-maladies à prions; Paris, France; 6CNRS UMR 7225; Paris, France; 7Université Pierre et Marie Curie-Paris; Paris, France†Presenting author; Email: jean-philippe.brandel@psl.aphp.fr
Active surveillance of Creutzfeldt-Jakob disease, which has been implemented in European countries, requires important human resources and funding. As the epidemic of variant CJD due to the bovine spongiform encephalopathy agent is in decline, less intense surveillance systems, based on routine mortality or morbidity registers, could be considered. CJD data collected by the French national CJD surveillance centre were compared with CJD data registered in the national mortality statistics. From
2000 to 2008, the two sources reported fairly similar numbers of CJD deaths (1188 and 1221 for the surveillance centre and the mortality register respectively). However, analysis of individual data showed important between-sources disagreements. At least 13% of CJD reported by the mortality register were false positive diagnoses and 21.6% of the CJD cases diagnosed by the surveillance centre were not registered as CJD in the national mortality statistics. For 126 deaths registered as CJD in the mortality statistics that had not been notified to the surveillance center, available data did not allow CJD diagnosis to be confirmed or excluded. One out of 22 variant CJD cases was not reported as having any type of CJD in the mortality statistics. Without further investigation, the conclusion could have been that CJD surveillance could be based on routinely collected mortality data. Considering the uncertainties on the evolution of the vCJD epidemics and the emergence of novel prion diseases in animals consumed by humans with zoonotic potential, these results support the idea that an active surveillance should be maintained to provide reliable data on future cases that may arise in next decades.
Risk.10: CSF Proteins and Diagnosis of Sporadic Creutzfeldt-Jakob Disease in Canada
Michael B. Coulthart,1,† Gerard H. Jansen,2 Elina Olsen,3 Deborah L. Godal,1 Tim Connolly,3 Bernard C. Choi,3 Zheng Wang3 and Neil R. Cashman4
1Public Health Agency of Canada; Winnipeg, MB Canada; 2University of Ottawa; Ottawa, ON Canada; 3Public Health Agency of Canada; Ottawa, ON Canada; 4University of British Columbia; Vancouver, BC Canada†Presenting author; Email: michael.coulthart@phac-aspc.gc.ca
Background. With its range of initial symptoms that may accompany other conditions, and a frequent need for timely diagnosis, sporadic Creutzfeldt-Jakob disease (sCJD) can present the clinician with significant challenges. Particularly widely employed for this purpose are assays for certain brain proteins in cerebrospinal fluid (CSF). Data are needed to better support systematic revision of diagnostic probabilities for sCJD on the basis of CSF protein assay results, in patient populations that also include diverse subacute encephalopathies eliciting a clinical suspicion of sCJD.
Methods. CSF 14-3-3, total Tau and S-100B proteins were studied prospectively in 948 Canadian patients suspected of having sCJD, including 121 with autopsy-confirmed sCJD and 827 with probable non-CJD diagnoses. Various metrics of diagnostic accuracy including sensitivity, specificity, predictive values and likelihood ratios were estimated.
Results. Estimated diagnostic accuracy for individual markers were mostly consistent with those of previously published studies at optimal cutoff thresholds for this study population (empirically defined for 14-3-3 immunoblot; 976 pg/mL for Tau; 2.5 ng/mL for S-100B). Sensitivity and specificity estimates respectively at these thresholds were 0.88 (95% CI, 0.81–0.93) and 0.71 (0.68–0.74) for 14-3-3; 0.90 (0.83–0.95) and 0.87 (0.85–0.90) for Tau; and 0.86 (0.78–0.91) and 0.86 (0.84–0.89) for S-100B; thus, the only outlier was 14-3-3 specificity (~0.7). Positive likelihood ratio (LR+) estimates were low to moderate: 3.0 (2.8–3.3) for 14-3-3; 7.1 (6.6–7.6) for Tau and 6.3 (5.8–6.8) for S-100B at optimal cutoff thresholds. Negative likelihood ratios were moderate: 0.17 (0.10–0.30) for 14-3-3; 0.12 (0.07–0.2) for Tau; and 0.17 (0.10–0.30) for S-100B. Interval LR estimates strengthened accuracy for patient subsets—for example, 31.4% of sCJD patients displayed extreme CSF Tau levels (>12 000 pg/mL), associated with an LR of 64.0 (23.3–175.9). Combining Tau and S-100B results, even at intermediate values, also enhanced accuracy; e.g., LR+ = 55.6 (20.1–153.7) with Tau > 5000 pg/mL and S-100B > 5.0 ng/mL.
Conclusions. CSF Tau and S-100B show comparable or better diagnostic accuracy compared to 14-3-3 in a heterogeneous patient population with low average pre-test probability of sCJD. Tau and S-100B may be optimal choices for many sCJD case investigations. Reporting of quantitative assay results as well as combining Tau and S-100B could enhance the clinical utility of surveillance case definitions for sCJD.
Risk.12: Transmission of Atypical Italian sCJD Case to Humanized Mice Reveals a Novel Infectious Strain
Roberta Galeno,1,† Marco Sbriccoli,1 Loredana Ingrosso,1 Silvia Graziano,1 Angelina Valanzano,1 Anna Poleggi,1 Angela De Pascalis,1 Anna Ladogana,1 Franco Cardone,1 Maria Puopolo,1 Gianluigi Zanusso2 and Maurizio Pocchiari1
1Istituto Superiore di Sanità; Rome, Italy; 2University of Verona; Verona, Italy†Presenting author; Email: roberta.galeno@iss.it
Sporadic Creutzfeldt-Jakob disease (sCJD) is a neurodegenerative prion disorder with uncertain etiology characterized by a typical combination of clinical symptoms, neuropathological lesions, and by the deposition of the pathological protein PrPTSE in the brain.
The vast majority of patients affected by sCJD can be categorized according to the genotype at the polymorphic position
129 of PrP (methionine or valine) and to the molecular mass of PrPTSE (type 1 or 2, corresponding to 21 or 19 kDa), yielding six possible combinations (MM1, MM2, VV1, VV2, MV1, and MV2) that associate with five clinico-pathological variants. Transmission studies of these sCJD subtypes into transgenic mice expressing the human prion protein allowed to identify four different infectious strains, which can partly explain the heterogeneity observed in sCJD patients.1
We recently described a novel molecular and pathological phenotype of sCJD (MV at position 129 of PrP), associated with an unprecedented electrophoretic pattern of PrPTSE characterized by the absence of the highly glycosylated isoform. In this work, we sought to characterize the prion strain associated with this atypical case by intracerebral inoculation into gene-targeted transgenic mice (HuTg) carrying the human PRNP gene with the three 129 genotype combinations. For comparison, three Italian sCJD cases heterozygous at position 129 of the prion protein, belonging to different subtypes (MV1, MV1/2, MV2), were transmitted to the same panel of transgenic mice. Survival times, attack rates, lesion profiles, and molecular analysis of the PrPTSE type recovered from mouse brains injected with the atypical case were compared with data from control animals. Mice inoculated with the atypical case displayed a restricted host tropism, with only a small number of VV animals that resulted PrPTSE-positive after an exceedingly long survival time. Interestingly, PrPTSE accumulated in brains from these mice lacks the diglycosylated band similar to that in sCJD inoculum, yet dissimilar to any other PrPTSE observed in HuTg mice by us and by other authors.1,2 Overall, these results strongly indicate that our atypical case associates with a new infectious strain of sCJD. Further investigations are needed to understand the possible connection with other human and animal prion diseases.
References
1. Bishop MT, Will RG, Manson JC. Defining sporadic Creutzfeldt-Jakob disease strains and their transmission properties. Proc Natl Acad Sci USA 2010; 107:12005-10.
2. Bishop MT, Hart P, Aitchison L, Baybutt HN, Plinston C, Thomson V, et al. Predicting susceptibility and incubation time of human-to-human transmission of vCJD. Lancet Neurol 2006; 5:393-8.
Risk.21: Thirty-Year Review of Prion Disease Surveillance in the United States
Robert C. Holman,1,† Ryan A. Maddox,1 Arianne M. Folkema,1 Arialdi M. Minino,2 Teresa A. Hammett,1 Kenneth D. Kochanek,2 James J. Sejvar,1 Ermias D. Belay1 and Lawrence B. Schonberger,1
1CDC; Atlanta, GA USA; 2CDC; Hyattsville, MD USA†Presenting author; Email: rholman@cdc.gov
Background. With the emergence of bovine spongiform encephalopathy/variant Creutzfeldt-Jakob disease (vCJD) in the UK, the Centers for Disease Control and Prevention began utilizing national mortality data with additional surveillance mechanisms to monitor US occurrences of human prion disease.
Objectives. To review US prion disease surveillance data.
Methods. We analyzed national mortality data for prion disease deaths (a surrogate for CJD incidence) among US residents for the 30 year period, 1979–2008, augmenting and extending these data through 2010 with information from other surveillance mechanisms (e.g., national neuropathology surveillance). We calculated age-adjusted and age-specific death rates per million persons; race-specific rates used data available beginning 1981. We age-adjusted death rates to the standard projected US 2000 population. www.landesbioscience.com Prion 131
Results. A total of 7,615 deaths during 1979–2008 were identified for an average annual age-adjusted rate of 0.98 cases per million persons. The highest rate (1.15) was observed in 1997; the highest number of reported cases was in 2008 (348). By race, the rate (1.06) among whites, who constituted 95% of the cases, was significantly higher than among blacks (0.40), Asian/Pacific Islanders (0.63) and American Indians/Alaska Natives (0.42). The rate (4.0) among persons =55 years old was strikingly higher than the rate (0.14) among persons <55 years old. The youngest decedent was age 21 years. None of the deaths during the 30 year period were reported with hereditary factor VIII or IX deficiency, thalassemia, or sickle cell disease. Through 2010, the only identified vCJD decedents among US residents were the three in 2004-2006 who were previously reported as likely infected in the UK or Saudi Arabia.
Conclusion. The annual age-adjusted US CJD death rates remained relatively stable over several decades although the most recent, complete, annual data show the highest number of cases. The absence of CJD in persons <20 years of age despite an estimated magnitude of 100,000 transfusion recipients <5 years of age who remained at risk during the surveillance period plus many times more such youngsters who received blood products and the absence of CJD in persons with hemophilia (current population ~20,000), thalassemia (~1,000) or sickle cell disease (~100,000) suggests the risk, if any, of blood-related CJD transmissions is likely very low. Racial differences in CJD rates deserve further investigation.
Risk.27: Creutzfeldt-Jakob Disease Among Hispanics in the United States, 1997–2008
Ryan A. Maddox,1,† Robert C. Holman,1 Arianne M. Folkema,1 Arialdi M. Minino,2 Teresa A. Hammett,1 Lawrence B. Schonberger1 and Ermias D. Belay1
1National Center for Zoonotic and Emerging Infectious Diseases; Centers for Disease Control and Prevention; Atlanta, GA USA; 2National Center for Health Statistics; Centers for Disease Control and Prevention; Hyattsville, MD USA†Presenting author; Email: rmaddox@cdc.gov
Introduction. At 16% of the US population, Hispanics make up the largest ethnic or racial minority in the country, and this proportion is expected to increase in the coming decades. The occurrence of Creutzfeldt-Jakob disease (CJD) among Americans of Hispanic ethnicity has not been widely investigated.
Methods. Hispanic CJD decedents of any age were identified from the US national multiple cause-of-death data and other sources for 1997–2008. Relevant portions of medical records and results from neuropathologic and genetic testing for Hispanic CJD decedents <55 years of age were obtained and reviewed, as available.
Results. During 1997–2008, 160 CJD decedents were identified as being of Hispanic ethnicity, for an average annual age-adjusted incidence of 0.65 per million population, an incidence significantly lower than that for non-Hispanics (RR =0.6; 95% CI 0.5–0.7). While 27 states reported at least one Hispanic decedent during the time period, almost half (47.5%) of the decedents were residents of California or Texas, the states with the highest Hispanic populations. A majority (55.0%) of the decedents were females, but the average annual age-adjusted incidence was slightly higher for males, although the difference was not significant. The median age at death was 64 years (range 36-93 years). Thirty-three Hispanic CJD decedents (20.6%) were <55 years of age, compared to 12.1% of cases in that age group among non-Hispanic CJD decedents; however, the average annual age-specific incidence for CJD decedents <55 years of age was significantly lower among Hispanics compared to non-Hispanics (0.08 compared to 0.17, respectively; p < 0.0001). Of the 33 young Hispanic CJD decedents, 21 (63.6%) had medical records and/or neuropathology reports available for review. Ten of these 21 cases (47.6%) had neuropathologic confirmation, including three decedents with familial CJD and one decedent with sporadic fatal insomnia.
Conclusions. Between 1997 and 2008, the reported CJD incidence among Hispanics in the US was significantly lower than that for non-Hispanics. This lower incidence may be at least partly due to underreporting of Hispanic ethnicity relative to surveys and censuses, and further study is warranted. Analyses of brain tissue remain important, especially considering that approximately half of the young Hispanic decedents with information available lacked CJD confirmation.
Risk.26: Sex Effect in Prion Diseases
Corinne Loeillet,1,† Pierre-Yves Boelle,2 Catherine Lemaire-Vieille,1 Philippe Naquet,3 Pierre Chambon,4 Marie-France Cesbron-Delauw,1 Alain-Jacques Valleron,2 Jean Gagnon1 and Jean-Yves Cesbron1
1CNRS LAPM 5163–Université Joseph Fourier; Grenoble, France; 2INSERM U 707–2 Université Pierre et Marie Curie–Paris 6; Paris, France; 3Centre d’Immunologie de Marseille-Luminy, INSERM-CNRS; Marseille, France; 4Institut de Génétique et de Biologie Moléculaire et Cellulaire, Université Louis Pasteur de Strasbourg; Strasbourg, France†Presenting author; Email: corinne.loeuillet@ujf-grenoble.fr
Despite large exposure to BSE in the UK, less than 180 patients had developed clinical vCJD by October 2009. This figure was closely anticipated in 2001, thanks to an epidemiological model whose main assumptions was that the risk of acquiring vCJD was exponentially decreasing during childhood, which was consistent with the age distribution of vCJD. Further investigation of the models showed that this decrease of risk during childhood could not be explained by the age variation of meat consumption, and was likely a consequence of an age dependent susceptibility to the disease. The more likely explanation for this strong age-susceptibility relationship during childhood is hormonal.
In this context, we investigated if there was a sex difference in human vCJD cases, and we used a mouse model to test a first hypothesis on the possible role of sexual hormones on the risk of prion diseases.
In the 167 vCJD cases reported in the UK as of January 2009, age at onset was significantly lower in women (two years) than in men after stratification on birth cohort. In C57/BL6N mice infected with ME-7 scrapie strain, incubation was shorter in females than in males. The incubation period increased in castrated male mice after intraperitoneal infection, but not after intracerebral inoculation. We also observed that androgen receptor deficient mice the incubation period of prion disease also increased after intraperitoneal inoculation. In contrast, in ovariectomised or estrogen receptor a defective female mice, no effect was observed on the incubation period of mouse prion disease.
These results show that androgens influence the prion diseases incubation period in a peripheral site.1
References
1. Loeuillet C, Boelle PY, Lemaire-Vieille C, Baldazza M, Naquet P, Chambon P, et al. Sex effect in mouse and human prion disease. J Infect Dis 2010; 202:648-54.
Risk.49: Creutzfeldt-Jakob Disease in Canada, 1998–2009
Zheng Wang,1,† Gerard Jansen,1, 2 Elina Olsen,1 Stacy Sabourin,1 Rolande D’Amour,1 Tim Connolly,1 Jennifer Kruse,1 Neil Cashman3 and Michael Coulthart1
1The Canadian Creutzfeldt-Jakob Disease Surveillance System; Public Health Agency of Canada; Ottawa, ON Canada; 2Department of Pathology; Ottawa Hospital; Ottawa, ON Canada; 3Brain Research Centre; University of British Columbia; Vancouver, BC Canada†Presenting author; Email: zheng.wang@phac-aspc.gc.ca
Background. Creutzfeldt-Jakob Disease (CJD) is a fatal, transmissible neurodegenerative disease with sporadic, genetic and acquired forms. In 1998, Canada launched comprehensive national CJD surveillance to assess the characteristics of CJD in Canada and its risks to the health of Canadians. This study describes the broad characteristics of CJD in Canada from 1998–2009.
Methods. Case ascertainment was based on internationally accepted criteria. Demographic information and risk-factor data were collected by standardized questionnaire and medical chart review. Poisson regression, descriptive analysis, and case investigation were employed.
Results. A total of 453 CJD deaths in Canadian residents were registered from 1998–2009. Four hundred and fifteen (92%) were sporadic (sCJD), 33 (7%) were genetic and five (1%) were acquired. Average annual sCJD mortality was 1.1 per million population, increasing gradually from 0.9 in 1999 to 1.4 in 2009 (P = 0.27). All provinces saw average annual mortalities ranging from 1.0 to 1.5 (P = 0.85), except three territories where population is small (~25,000 to ~45,000), sCJD occurred equally in both genders at 1.1. sCJD was rare under 50 years of age with only 11 cases identified (2.7%). Mortality increased after 50 and peaked at 8 per million in the 70–74 age group. Median age at death was 69 and median duration of illness was 4 months. Genetic TSE accounted for 33 deaths: 19 were GSS (P102L: 5, D202N: 2, P105T: 2, Q217R:1, A117V: 1, unknown mutation: 8); 13 were familial CJD (E200K: 9, D178N: 2, V203I: 1, V189I:1); one was FFI (D178N). Median age for genetic TSE was 59 and median duration of illness was 27 months. For the five acquired cases of CJD, four were associated with dura mater procedures (3 Lyodura, 1 Tutoplast) and were identified from 1998–2003 in patients aged 14–59. Investigation indicated the infections possibly occurred from 1981–1992 with incubation times from 10–16 years. One biochemically and neuropathologically confirmed variant CJD death occurred in 2002 in a person under 40 years old, likely acquired overseas.
Discussion and Conclusion. Characteristics of CJD in Canada are consistent with those observed in other countries. The increase in sCJD mortality can be at least partly attributed to increased awareness of CJD among referring clinicians. The finding of four dura matter associated CJD cases and one imported vCJD case in Canada demonstrate risks to Canadians from acquired CJD exist. Continued surveillance for iatrogenic risks and novel forms of CJD is warranted.
Risk.50: Investigating Dental Treatment as a Possible Risk Factor for Variant Creutzfeldt-Jakob Disease (vCJD) in the UK
Dawn Everington,1 Andrew Smith,2 Pauline Watt,1 Fiona Ord,1 Anna Molesworth,1 Robert Will1,† and Hester Ward1
1National CJD Surveillance Unit; Edinburgh, UK; 2College of Medical, Veterinary and Life Sciences; University of Glasgow; Glasgow, UK;†Presenting author; Email: r.g.will@ed.ac.uk
Introduction. The potential for vCJD transmission in the healthcare setting has raised concerns over the risk posed by dental surgery. The aim of this study was to determine whether dental treatment was a possible risk factor for vCJD.
Methods. Dental treatment records were collected from general dental practitioners or, where this was not possible, from NHS Dental Practice Board payment schedules. We looked for links between vCJD cases and whether there was an excess of dental treatment in vCJD cases compared with general population controls.
Results. Data were available for 49% (79/162) of cases and 82% (503/610) of controls. Two pairs of cases had attended the same dental practice, multiple treatment data were traced for one pair. While theoretically possible that the same instruments could have been used on both cases, after considering the type and timing of interventions we propose that the probability of cross-infection is very small. The review of specific dental treatments showed that there was no evidence that vCJD cases experienced an excess of any type of dental treatment compared with controls.
Conclusions. This study provided no compelling evidence of a strong association between dental treatment and vCJD, however because of the limited availability of dental information, and the possibility of undetected asymptomatic infection, we cannot exclude dental treatment as a possible risk factor for vCJD. We support current health policy to ensure that high standards of cleaning and sterilization of re-usable dental instruments are maintained.
http://www.prion2011.ca/files/PRION_2011_-_Posters_(May_5-11).pdf
CANADA CJD UPDATE 2011
CJD Deaths Reported by CJDSS1, 1994-20112 As of January 31, 2011
3. Final classification of 49 cases from 2009, 2010, 2011 is pending.
snip...
http://www.phac-aspc.gc.ca/hcai-iamss/cjd-mcj/cjdss-ssmcj/pdf/stats_0111-eng.pdf
USA 2011
USA
National Prion Disease Pathology Surveillance Center
Cases Examined1
(November 1, 2010)
Year Total Referrals2 Prion Disease Sporadic Familial Iatrogenic vCJD
1996 & earlier 51 33 28 5 0 0
1997 114 68 59 9 0 0
1998 87 51 43 7 1 0
1999 121 73 65 8 0 0
2000 146 103 89 14 0 0
2001 209 119 109 10 0 0
2002 248 149 125 22 2 0
2003 274 176 137 39 0 0
2004 325 186 164 21 0 13
2005 344 194 157 36 1 0
2006 383 197 166 29 0 24
2007 377 214 187 27 0 0
2008 394 231 205 25 0 0
2009 425 258 215 43 0 0
2010 333 213 158 33 0 0
TOTAL 38315 22656 1907 328 4 3
1 Listed based on the year of death or, if not available, on year of referral;
2 Cases with suspected prion disease for which brain tissue and/or blood (in familial cases) were submitted;
3 Disease acquired in the United Kingdom;
4 Disease was acquired in the United Kingdom in one case and in Saudi Arabia in the other case;
5 Includes 18 cases in which the diagnosis is pending, and 18 inconclusive cases;
6 Includes 23 (22 from 2010) cases with type determination pending in which the diagnosis of vCJD has been excluded.
http://www.cjdsurveillance.com/pdf/case-table.pdf
Please notice where sporadic CJD cases in 1996 went from 28 cases, to 215 cases in 2009, the highest recorded year to date. sporadic CJD is on a steady rise, and has been since 1996.
I also urge you to again notice these disturbing factors in lines 5 and 6 ;
5 Includes 18 cases in which the diagnosis is pending, and 18 inconclusive cases;
6 Includes 23 (22 from 2010) cases with type determination pending in which the diagnosis of vCJD has been excluded.
========end=====tss=====2011
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
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
Thursday, August 4, 2011
Terry Singeltary Sr. on the Creutzfeldt-Jakob Disease Public Health Crisis, Date aired: 27 Jun 2011
see video here ;
http://transmissiblespongiformencephalopathy.blogspot.com/2011/08/terry-singeltary-sr-on-creutzfeldt.html
Saturday, January 2, 2010
Human Prion Diseases in the United States January 1, 2010 ***FINAL***
http://prionunitusaupdate2008.blogspot.com/2010/01/human-prion-diseases-in-united-states.html
Manuscript Draft Manuscript Number: Title: HUMAN and ANIMAL TSE Classifications i.e. mad cow disease and the UKBSEnvCJD only theory Article Type: Personal View Corresponding Author: Mr. Terry S. Singeltary, Corresponding Author's Institution: na First Author: Terry S Singeltary, none Order of Authors: Terry S Singeltary, none; Terry S. Singeltary Abstract: TSEs have been rampant in the USA for decades in many species, and they all have been rendered and fed back to animals for human/animal consumption. I propose that the current diagnostic criteria for human TSEs only enhances and helps the spreading of human TSE from the continued belief of the UKBSEnvCJD only theory in 2007.
http://www.regulations.gov/fdmspublic/ContentViewer?objectId=090000648027c28e&disposition=attachment&contentType=pdf
my comments to PLosone here ;
http://www.plosone.org/annotation/listThread.action?inReplyTo=info%3Adoi%2F10.1371%2Fannotation%2F04ce2b24-613d-46e6-9802-4131e2bfa6fd&root=info%3Adoi%2F10.1371%2Fannotation%2F04ce2b24-613d-46e6-9802-4131e2bfa6fd
Sunday, August 09, 2009
CJD...Straight talk with...James Ironside...and...Terry Singeltary... 2009
http://creutzfeldt-jakob-disease.blogspot.com/2009/08/cjdstraight-talk-withjames.html
Tuesday, August 18, 2009
BSE-The Untold Story - joe gibbs and singeltary 1999 - 2009
http://madcowusda.blogspot.com/2009/08/bse-untold-story-joe-gibbs-and.html
Friday, February 11, 2011
Creutzfeldt-Jakob disease (CJD) biannual update (2010/1) Emerging infections/CJD
http://creutzfeldt-jakob-disease.blogspot.com/2011/02/creutzfeldt-jakob-disease-cjd-biannual.html
Friday, April 15, 2011
PRION TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY PROJECTS, RESEARCH FUNDING, BSE VOLUNTARY TESTING UPDATE IN NORTH AMERICA 2011
http://prionunitusaupdate2008.blogspot.com/2011/04/prion-transmissible-spongiform.html
PRION TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY RESEARCH FUNDING U.S.A.
COMPARE TO USA PRION FUNDING 2011
"which includes the ___elimination___ of Prion activities ($5,473,000),"
All Other Emerging and Zoonotic Infectious Diseases CDC‘s FY 2012 request of $52,658,000 for all other emerging and zoonotic infectious disease activities is a decrease of $13,607,000 below the FY 2010 level, which includes the elimination of Prion activities ($5,473,000), a reduction for other cross-cutting infectious disease activities, and administrative savings. These funds support a range of critical emerging and zoonotic infectious disease programs such Lyme Disease, Chronic Fatigue Syndrome, and Special Pathogens, as well as other activities described below.
http://www.cdc.gov/fmo/topic/Budget%20Information/appropriations_budget_form_pdf/FY2012_CDC_CJ_Final.pdf
THE PATHOLOGICAL PROTEIN
BY Philip Yam
Yam Philip Yam News Editor Scientific American www.sciam.com
Answering critics like Terry Singeltary, who feels that the U.S. under- counts CJD, Schonberger conceded that the current surveillance system has errors but stated that most of the errors will be confined to the older population.
CHAPTER 14
Laying Odds
Are prion diseases more prevalent than we thought?
Researchers and government officials badly underestimated the threat that mad cow disease posed when it first appeared in Britain. They didn't think bovine spongiform encephalopathy was a zoonosis-an animal disease that can sicken people. The 1996 news that BSE could infect humans with a new form of Creutzfeldt-Jakob disease stunned the world. It also got some biomedical researchers wondering whether sporadic CJD may really be a manifestation of a zoonotic sickness. Might it be caused by the ingestion of prions, as variant CJD is?
Revisiting Sporadic CJD
It's not hard to get Terry Singeltary going. "I have my conspiracy theories," admitted the 49-year-old Texan.1 Singeltary is probably the nation's most relentless consumer advocate when it comes to issues in prion diseases. He has helped families learn about the sickness and coordinated efforts with support groups such as CJD Voice and the CJD Foundation. He has also connected with others who are critical of the American way of handling the threat of prion diseases. Such critics include Consumers Union's Michael Hansen, journalist John Stauber, and Thomas Pringle, who used to run the voluminous www.madcow. org Web site. These three lend their expertise to newspaper and magazine stories about prion diseases, and they usually argue that prions represent more of a threat than people realize, and that the government has responded poorly to the dangers because it is more concerned about protecting the beef industry than people's health.
Singeltary has similar inclinations. ...
snip...
THE PATHOLOGICAL PROTEIN
Hardcover, 304 pages plus photos and illustrations. ISBN 0-387-95508-9
June 2003
BY Philip Yam
CHAPTER 14 LAYING ODDS
Answering critics like Terry Singeltary, who feels that the U.S. under- counts CJD, Schonberger conceded that the current surveillance system has errors but stated that most of the errors will be confined to the older population.
http://www.thepathologicalprotein.com/
http://books.google.com/books?id=ePbrQNFrHtoC&pg=PA223&lpg=PA223&dq=the+pathological+protein+laying+odds+It%E2%80%99s+not+hard+to+get+Terry+Singeltary+going&source=bl&ots=um0PFAZSZD&sig=JWaGR7M7-1WeAr2qAXq8D6J_jak&hl=en&ei=MhtjS8jMJM2ztgeFoa2iBg&sa=X&oi=book_result&ct=result&resnum=1&ved=0CAcQ6AEwAA#v=onepage&q=&f=false
http://www.springerlink.com/content/r2k2622661473336/fulltext.pdf?page=1
http://www.thepathologicalprotein.com/
http://prionunitusaupdate2008.blogspot.com/2009/04/national-prion-disease-pathology.html
Newsdesk The Lancet Infectious Diseases, Volume 3, Issue 8, Page 463, August 2003 doi:10.1016/S1473-3099(03)00715-1Cite or Link Using DOI
Tracking spongiform encephalopathies in North America
Xavier Bosch
"My name is Terry S Singeltary Sr, and I live in Bacliff, Texas. I lost my mom to hvCJD (Heidenhain variant CJD) and have been searching for answers ever since. What I have found is that we have not been told the truth. CWD in deer and elk is a small portion of a much bigger problem." 49-year-old Singeltary is one of a number of people who have remained largely unsatisfied after being told that a close relative died from a rapidly progressive dementia compatible with spontaneous Creutzfeldt-Jakob disease (CJD). So he decided to gather hundreds of documents on transmissible spongiform encephalopathies (TSE) and realised that if Britons could get variant CJD from bovine spongiform encephalopathy (BSE), Americans might get a similar disorder from chronic wasting disease (CWD)-the relative of mad cow disease seen among deer and elk in the USA. Although his feverish.
http://linkinghub.elsevier.com/retrieve/pii/S1473309903007151
http://www.thelancet.com/journals/laninf/article/PIIS1473-3099(03)00715-1/fulltext
http://www.mdconsult.com/das/article/body/180784492-2/jorg=journal&source=&sp=13979213&sid=0/N/368742/1.html?issn=14733099
Diagnosis and Reporting of Creutzfeldt-Jakob Disease Singeltary, Sr et al. JAMA.2001; 285: 733-734. Vol. 285 No. 6, February 14, 2001 JAMA
Diagnosis and Reporting of Creutzfeldt-Jakob Disease
To the Editor: In their Research Letter, Dr Gibbons and colleagues1 reported that the annual US death rate due to Creutzfeldt-Jakob disease (CJD) has been stable since 1985. These estimates, however, are based only on reported cases, and do not include misdiagnosed or preclinical cases. It seems to me that misdiagnosis alone would drastically change these figures. An unknown number of persons with a diagnosis of Alzheimer disease in fact may have CJD, although only a small number of these patients receive the postmortem examination necessary to make this diagnosis. Furthermore, only a few states have made CJD reportable. Human and animal transmissible spongiform encephalopathies should be reportable nationwide and internationally.
Terry S. Singeltary, Sr Bacliff, Tex
1. Gibbons RV, Holman RC, Belay ED, Schonberger LB. Creutzfeldt-Jakob disease in the United States: 1979-1998. JAMA. 2000;284:2322-2323. FREE FULL TEXT
http://jama.ama-assn.org/cgi/content/extract/285/6/733?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=singeltary&searchid=1&FIRSTINDEX=0&resourcetype=HWCIT
http://jama.ama-assn.org/cgi/content/full/285/6/733?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=singeltary&searchid=1&FIRSTINDEX=0&resourcetype=HWCIT
DER SPIEGEL (9/2001) - 24.02.2001 (9397 Zeichen) USA: Loch in der Mauer Die BSE-Angst erreicht Amerika: Trotz strikter Auflagen gelangte in Texas verbotenes Tiermehl ins Rinderfutter - die Kontrollen der Aufsichtsbehördensind lax.Link auf diesen Artikel im Archiv:
http://service.spiegel.de/digas/find?DID=18578755
"Löcher wie in einem Schweizer Käse" hat auch Terry Singeltary im Regelwerk der FDA ausgemacht. Der Texaner kam auf einem tragischen Umweg zu dem Thema: Nachdem seine Mutter 1997 binnen weniger Wochen an der Creutzfeldt-Jakob-Krankheit gestorben war, versuchte er, die Ursachen der Infektion aufzuspüren. Er klagte auf die Herausgabe von Regierungsdokumenten und arbeitete sich durch Fachliteratur; heute ist er überzeugt, dass seine Mutter durch die stetige Einnahme von angeblich kräftigenden Mitteln erkrankte, in denen - völlig legal - Anteile aus Rinderprodukten enthalten sind.
Von der Fachwelt wurde Singeltary lange als versponnener Außenseiter belächelt. Doch mittlerweile sorgen sich auch Experten, dass ausgerechnet diese verschreibungsfreien Wundercocktails zur Stärkung von Intelligenz, Immunsystem oder Libido von den Importbeschränkungen ausgenommen sind. Dabei enthalten die Pillen und Ampullen, die in Supermärkten verkauft werden, exotische Mixturen aus Rinderaugen; dazu Extrakte von Hypophyse oder Kälberföten, Prostata, Lymphknoten und gefriergetrocknetem Schweinemagen. In die USA hereingelassen werden auch Blut, Fett, Gelatine und Samen. Diese Stoffe tauchen noch immer in US-Produkten auf, inklusive Medizin und Kosmetika. Selbst in Impfstoffen waren möglicherweise gefährliche Rinderprodukte enthalten. Zwar fordert die FDA schon seit acht Jahren die US-Pharmaindustrie auf, keine Stoffe aus Ländern zu benutzen, in denen die Gefahr einer BSE-Infizierung besteht. Aber erst kürzlich verpflichteten sich fünf Unternehmen, darunter Branchenführer wie GlaxoSmithKline, Aventis und American Home Products, ihre Seren nur noch aus unverdächtigem Material herzustellen.
"Its as full of holes as Swiss Cheese" says Terry Singeltary of the FDA regulations. ...
http://www.spiegel.de/spiegel/print/d-18578755.html
http://wissen.spiegel.de/wissen/image/show.html?did=18578755&aref=image024/E0108/SCSP200100901440145.pdf&thumb=false
http://service.spiegel.de/digas/servlet/find/DID=18578755
Suspect symptoms
What if you can catch old-fashioned CJD by eating meat from a sheep infected with scrapie?
28 Mar 01
Like lambs to the slaughter 31 March 2001 by Debora MacKenzie Magazine issue 2284. Subscribe and get 4 free issues. FOUR years ago, Terry Singeltary watched his mother die horribly from a degenerative brain disease. Doctors told him it was Alzheimer's, but Singeltary was suspicious. The diagnosis didn't fit her violent symptoms, and he demanded an autopsy. It showed she had died of sporadic Creutzfeldt-Jakob disease.
Most doctors believe that sCJD is caused by a prion protein deforming by chance into a killer. But Singeltary thinks otherwise. He is one of a number of campaigners who say that some sCJD, like the variant CJD related to BSE, is caused by eating meat from infected animals. Their suspicions have focused on sheep carrying scrapie, a BSE-like disease that is widespread in flocks across Europe and North America.
Now scientists in France have stumbled across new evidence that adds weight to the campaigners' fears. To their complete surprise, the researchers found that one strain of scrapie causes the same brain damage in mice as sCJD.
"This means we cannot rule out that at least some sCJD may be caused by some strains of scrapie," says team member Jean-Philippe Deslys of the French Atomic Energy Commission's medical research laboratory in Fontenay-aux-Roses, south-west of Paris. Hans Kretschmar of the University of Göttingen, who coordinates CJD surveillance in Germany, is so concerned by the findings that he now wants to trawl back through past sCJD cases to see if any might have been caused by eating infected mutton or lamb.
Scrapie has been around for centuries and until now there has been no evidence that it poses a risk to human health. But if the French finding means that scrapie can cause sCJD in people, countries around the world may have overlooked a CJD crisis to rival that caused by BSE.
Deslys and colleagues were originally studying vCJD, not sCJD. They injected the brains of macaque monkeys with brain from BSE cattle, and from French and British vCJD patients. The brain damage and clinical symptoms in the monkeys were the same for all three. Mice injected with the original sets of brain tissue or with infected monkey brain also developed the same symptoms.
As a control experiment, the team also injected mice with brain tissue from people and animals with other prion diseases: a French case of sCJD; a French patient who caught sCJD from human-derived growth hormone; sheep with a French strain of scrapie; and mice carrying a prion derived from an American scrapie strain. As expected, they all affected the brain in a different way from BSE and vCJD. But while the American strain of scrapie caused different damage from sCJD, the French strain produced exactly the same pathology.
"The main evidence that scrapie does not affect humans has been epidemiology," says Moira Bruce of the neuropathogenesis unit of the Institute for Animal Health in Edinburgh, who was a member of the same team as Deslys. "You see about the same incidence of the disease everywhere, whether or not there are many sheep, and in countries such as New Zealand with no scrapie." In the only previous comparisons of sCJD and scrapie in mice, Bruce found they were dissimilar.
But there are more than 20 strains of scrapie, and six of sCJD. "You would not necessarily see a relationship between the two with epidemiology if only some strains affect only some people," says Deslys. Bruce is cautious about the mouse results, but agrees they require further investigation. Other trials of scrapie and sCJD in mice, she says, are in progress.
People can have three different genetic variations of the human prion protein, and each type of protein can fold up two different ways. Kretschmar has found that these six combinations correspond to six clinical types of sCJD: each type of normal prion produces a particular pathology when it spontaneously deforms to produce sCJD.
But if these proteins deform because of infection with a disease-causing prion, the relationship between pathology and prion type should be different, as it is in vCJD. "If we look at brain samples from sporadic CJD cases and find some that do not fit the pattern," says Kretschmar, "that could mean they were caused by infection."
There are 250 deaths per year from sCJD in the US, and a similar incidence elsewhere. Singeltary and other US activists think that some of these people died after eating contaminated meat or "nutritional" pills containing dried animal brain. Governments will have a hard time facing activists like Singeltary if it turns out that some sCJD isn't as spontaneous as doctors have insisted.
Deslys's work on macaques also provides further proof that the human disease vCJD is caused by BSE. And the experiments showed that vCJD is much more virulent to primates than BSE, even when injected into the bloodstream rather than the brain. This, says Deslys, means that there is an even bigger risk than we thought that vCJD can be passed from one patient to another through contaminated blood transfusions and surgical instruments.
http://www.newscientist.com/article/mg16922840.300-like-lambs-to-the-slaughter.html
2 January 2000
British Medical Journal
U.S. Scientist should be concerned with a CJD epidemic in the U.S., as well
http://www.bmj.com/cgi/eletters/320/7226/8/b#6117
15 November 1999
British Medical Journal
vCJD in the USA * BSE in U.S.
http://www.bmj.com/cgi/eletters/319/7220/1312/b#5406
2006
USA sporadic CJD cases rising ;
There is a growing number of human CJD cases, and they were presented last week in San Francisco by Luigi Gambatti(?) from his CJD surveillance collection.
He estimates that it may be up to 14 or 15 persons which display selectively SPRPSC and practically no detected RPRPSC proteins.
http://www.fda.gov/ohrms/dockets/ac/06/transcripts/1006-4240t1.htm
http://www.fda.gov/ohrms/dockets/ac/06/transcripts/2006-4240t1.pdf
Thursday, July 08, 2010
GLOBAL CLUSTERS OF CREUTZFELDT JAKOB DISEASE - A REVIEW 2010
http://creutzfeldt-jakob-disease.blogspot.com/2010/07/global-clusters-of-creutzfeldt-jakob.html
Wednesday, June 29, 2011
TSEAC Meeting August 1, 2011 donor deferral vCJD...
http://tseac.blogspot.com/2011/06/tseac-meeting-august-1-2011-donor.html
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