TSENEWS
Sensitive detection of prion proteins in blood
The incidence of BSE cases in cattle has declined, but the risk of contracting the human form of BSE, vCJD, remains a serious threat. In addition to eating contaminated beef, the disease can be also transmitted from one human being to another through organ and tissue transplantations and blood transfusions. The latter harbors an extreme potential risk, since blood from one donor can infect multiple receivers. Recent research has demonstrated that sensitive detection of prions in blood is possible. Using a combination of Prionics antibody 15B3 and prion amplification, the blood test is 10,000 times more sensitive than previously reported assays.
Prion diseases are caused by aberrantly folded prion proteins that accumulate in the brain, resulting in serious brain damage. Several scientific groups have reported long incubation times for vCJD before clinical symptoms appear. Therefore, an individual incubating vCJD can donate blood and spread the disease to multiple receivers. As low levels of prions are expected to be present in the blood of vCJD patients, sensitive detection of disease-specific prion proteins is of great importance for the safety of human blood donations. A recent publication by the group of Byron Caughey describes a new and very sensitive method for the detection of disease-specific prion proteins in blood or plasma. This eQuIC assay uses amplification of prions together with a concentration step using the Prionics 15B3 antibody.
10,000 fold more sensitive The monoclonal 15B3 antibody (mAb 15B3), developed by Prionics, has been shown to specifically recognize the disease-specific form of the prion protein (PrPSc). In the publication of Caughey and his group, the mAb 15B3 was used to “fish” PrPSc from a blood sample. This concentration step alone, however, did not suffice for the detection of prions in the blood. The researchers therefore used the quaking-induced conversion method to amplify disease-specific prions in the concentrated sample. This combination of concentration and amplification, which the researchers call eQuIC, resulted in a 10,000 fold more sensitive assay than those previously reported. Dilutions of 1014-fold, containing ~2 attogram per milliliter of proteinase K-resistant prion protein, were readily detected.
About the is eQuIC method The method used for prion amplification is the quaking-induced conversion (QuIC) reaction. The method is a cell-free conversion reaction of PrPC to PrPSc in multiwell plates. PrPSc present in the (blood) sample acts as a seed for the conversion of recombinant PrP added to the reaction as a substrate. PrPSc complexes formed in the tube are then disrupted by shaking, providing further scaffolds for prion protein conversion. In the real-time quaking-induced conversion, detection of formed PrPSc is based on thioflavin T fluorescence which is enhanced when bound to prion amyloids. Caughey and colleagues combined the real-time quaking-induced conversion with prior immunoprecipitation using mAb 15B3 and called the method enhanced real-time Quaking-Induced Conversion (eQuIC).
http://escope.prionics.com/issue/2011-august-2/
Prion Disease Blood Test Using Immunoprecipitation and Improved Quaking-Induced Conversion
Christina D. Orrú,a Jason M. Wilham,a Lynne D. Raymond,a Franziska Kuhn,b Björn Schroeder,b Alex J. Raeber,b and Byron Caugheya Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA,a and Prionics AG, Zurich, Switzerlandb
ABSTRACT
A key challenge in managing transmissible spongiform encephalopathies (TSEs) or prion diseases in medicine, agriculture, and wildlife biology is the development of practical tests for prions that are at or below infectious levels. Of particular interest are tests capable of detecting prions in blood components such as plasma, but blood typically has extremely low prion concentrations and contains inhibitors of the most sensitive prion tests. One of the latter tests is quaking-induced conversion (QuIC), which can be as sensitive as in vivo bioassays, but much more rapid, higher throughput, and less expensive. Now we have integrated antibody 15B3-based immunoprecipitation with QuIC reactions to increase sensitivity and isolate prions from inhibitors such as those in plasma samples. Coupling of immunoprecipitation and an improved real-time QuIC reaction dramatically enhanced detection of variant Creutzfeldt-Jakob disease (vCJD) brain tissue diluted into human plasma. Dilutions of 1014-fold, containing ~2 attogram (ag) per ml of proteinase K-resistant prion protein, were readily detected, indicating ~10,000- fold greater sensitivity for vCJD brain than has previously been reported. We also discriminated between plasma and serum samples from scrapie-infected and uninfected hamsters, even in early preclinical stages. This combined assay, which we call “enhanced QuIC” (eQuIC), markedly improves prospects for routine detection of low levels of prions in tissues, fluids, or environmental samples.
IMPORTANCE
Transmissible spongiform encephalopathies (TSEs) are largely untreatable and are difficult to diagnose definitively prior to irreversible clinical decline or death. The transmissibility of TSEs within and between species highlights the need for practical tests for even the smallest amounts of infectivity. A few sufficiently sensitive in vitro methods have been reported, but most have major limitations that would preclude their use in routine diagnostic or screening applications. Our new assay improves the outlook for such critical applications. We focused initially on blood plasma because a practical blood test for prions would be especially valuable for TSE diagnostics and risk reduction. Variant Creutzfeldt-Jakob disease (vCJD) in particular has been transmitted between humans via blood transfusions. Enhanced real-time quaking-induced conversion (eQuIC) provides by far the most sensitive detection of vCJD to date. The 15B3 antibody binds prions of multiple species, suggesting that our assay may be useful for clinical and fundamental studies of a variety of TSEs of humans and animals. Received 8 April 2011 Accepted 12 April 2011 Published 10 May 2011 Citation Orrú CD, et al. 2011. Prion disease blood test using immunoprecipitation and improved quaking-induced conversion. mBio 2(3):e00078-11. doi:10.1128/mBio.00078- 11. Editor Reed Wickner, National Institutes of Health Copyright © 2011 Orrú et al. This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported License, which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original author and source are credited. Address correspondence to Byron Caughey, bcaughey@nih.gov.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3101782/pdf/mBio.00078-11.pdf
Friday, July 29, 2011
Real-time quaking-induced conversion A highly sensitive assay for prion detection
http://transmissiblespongiformencephalopathy.blogspot.com/2011/07/real-time-quaking-induced-conversion.html
Saturday, July 23, 2011
CATTLE HEADS WITH TONSILS, BEEF TONGUES, SPINAL CORD, SPECIFIED RISK MATERIALS (SRM's) AND PRIONS, AKA MAD COW DISEASE
http://transmissiblespongiformencephalopathy.blogspot.com/2011/07/cattle-heads-with-tonsils-beef-tongues.html
Saturday, November 6, 2010
TAFS1 Position Paper on Position Paper on Relaxation of the Feed Ban in the EU Berne, 2010 TAFS
INTERNATIONAL FORUM FOR TRANSMISSIBLE ANIMAL DISEASES AND FOOD SAFETY a non-profit Swiss Foundation
http://madcowfeed.blogspot.com/2010/11/tafs1-position-paper-on-position-paper.html
Archive Number 20101206.4364 Published Date 06-DEC-2010 Subject PRO/AH/EDR> Prion disease update 2010 (11)
PRION DISEASE UPDATE 2010 (11)
http://www.promedmail.org/pls/apex/f?p=2400:1001:5492868805159684::NO::F2400_P1001_BACK_PAGE,F2400_P1001_PUB_MAIL_ID:1000,86129
Thursday, July 28, 2011
An Update on the Animal Disease Traceability Framework July 27, 2011
http://naiscoolyes.blogspot.com/2011/07/update-on-animal-disease-traceability.html
Saturday, June 25, 2011
Transmissibility of BSE-L and Cattle-Adapted TME Prion Strain to Cynomolgus Macaque
"BSE-L in North America may have existed for decades"
http://transmissiblespongiformencephalopathy.blogspot.com/2011/06/transmissibility-of-bse-l-and-cattle.html
Over the next 8-10 weeks, approximately 40% of all the adult mink on the farm died from TME.
snip...
The rancher was a ''dead stock'' feeder using mostly (>95%) downer or dead dairy cattle...
http://web.archive.org/web/20030516051623/http://www.bseinquiry.gov.uk/files/mb/m09/tab05.pdf
Sunday, June 26, 2011
Risk Analysis of Low-Dose Prion Exposures in Cynomolgus Macaque
http://transmissiblespongiformencephalopathy.blogspot.com/2011/06/risk-analysis-of-low-dose-prion.html
Thursday, June 23, 2011
Experimental H-type bovine spongiform encephalopathy characterized by plaques and glial- and stellate-type prion protein deposits
http://transmissiblespongiformencephalopathy.blogspot.com/2011/06/experimental-h-type-bovine-spongiform.html
Thursday, July 21, 2011
A Second Case of Gerstmann-Sträussler-Scheinker Disease Linked to the G131V Mutation in the Prion Protein Gene in a Dutch Patient Journal of Neuropathology & Experimental Neurology:
August 2011 - Volume 70 - Issue 8 - pp 698-702
http://transmissiblespongiformencephalopathy.blogspot.com/2011/07/second-case-of-gerstmann-straussler.html
Saturday, August 14, 2010
BSE Case Associated with Prion Protein Gene Mutation (g-h-BSEalabama) and VPSPr PRIONPATHY
(see mad cow feed in COMMERCE IN ALABAMA...TSS)
http://prionpathy.blogspot.com/2010/08/bse-case-associated-with-prion-protein.html
Wednesday, June 15, 2011
Galveston, Texas - Isle port moves through thousands of heifers headed to Russia, none from Texas, Alabama, or Washington, due to BSE risk factor
http://transmissiblespongiformencephalopathy.blogspot.com/2011/06/galveston-texas-isle-port-moves-through.html
Thursday, July 28, 2011
An Update on the Animal Disease Traceability Framework July 27, 2011
http://naiscoolyes.blogspot.com/2011/07/update-on-animal-disease-traceability.html
Monday, June 27, 2011
Zoonotic Potential of CWD: Experimental Transmissions to Non-Human Primates
http://chronic-wasting-disease.blogspot.com/2011/06/zoonotic-potential-of-cwd-experimental.html
Thursday, May 26, 2011
Travel History, Hunting, and Venison Consumption Related to Prion Disease Exposure, 2006-2007 FoodNet Population Survey
Journal of the American Dietetic Association Volume 111, Issue 6 , Pages 858-863, June 2011.
http://transmissiblespongiformencephalopathy.blogspot.com/2011/05/travel-history-hunting-and-venison.html
Thursday, July 14, 2011
Histopathological Studies of "CH1641-Like" Scrapie Sources Versus Classical Scrapie and BSE Transmitted to Ovine Transgenic Mice (TgOvPrP4)
http://transmissiblespongiformencephalopathy.blogspot.com/2011/07/histopathological-studies-of-ch1641.html
Monday, June 20, 2011 2011
Annual Conference of the National Institute for Animal Agriculture ATYPICAL NOR-98 LIKE SCRAPIE UPDATE USA
http://nor-98.blogspot.com/2011/06/2011-annual-conference-of-national.html
Monday, June 27, 2011
Comparison of Sheep Nor98 with Human Variably Protease-Sensitive Prionopathy and Gerstmann-Sträussler-Scheinker Disease
http://prionopathy.blogspot.com/2011/06/comparison-of-sheep-nor98-with-human.html
Thursday, June 2, 2011
USDA scrapie report for April 2011 NEW ATYPICAL NOR-98 SCRAPIE CASES Pennsylvania AND California
http://nor-98.blogspot.com/2011/06/usda-scrapie-report-for-april-2011-new.html
Saturday, March 5, 2011
MAD COW ATYPICAL CJD PRION TSE CASES WITH CLASSIFICATIONS PENDING ON THE RISE IN NORTH AMERICA
http://transmissiblespongiformencephalopathy.blogspot.com/2011/03/mad-cow-atypical-cjd-prion-tse-cases.html
Tuesday, April 26, 2011
sporadic CJD RISING Text and figures of the latest annual report of the NCJDRSU covering the period 1990-2009 (published 11th March 2011)
http://creutzfeldt-jakob-disease.blogspot.com/2011/04/sporadic-cjd-rising-text-and-figures-of.html
Thursday, August 4, 2011
Terry Singeltary Sr. on the Creutzfeldt-Jakob Disease Public Health Crisis, Date aired: 27 Jun 2011
http://transmissiblespongiformencephalopathy.blogspot.com/2011/08/terry-singeltary-sr-on-creutzfeldt.html
Friday, August 12, 2011
Creutzfeldt-Jakob disease (CJD) biannual update (2011/2), Incidents Panel, National Anonymous Tonsil Archive
http://transmissiblespongiformencephalopathy.blogspot.com/2011/08/creutzfeldt-jakob-disease-cjd-biannual.html
TSS
Saturday, August 13, 2011
Friday, August 12, 2011
Creutzfeldt-Jakob disease (CJD) biannual update (2011/2), Incidents Panel, National Anonymous Tonsil Archive
Creutzfeldt-Jakob disease (CJD) biannual update (2011/2) This six-monthly report provides an update on reports of incidents of potential iatrogenic (healthcare-acquired) exposure to CJD, and on the National Anonymous Tonsil Archive. The data are correct as of 12 July 2011.
For numbers of CJD case reports, readers should consult data provided by the National CJD Research and Surveillance Unit (NCJDRSU), Edinburgh [1]. The latest yearly analysis of vCJD reports (onsets and deaths) is also available from the NCJDRSU website [2].
Reports of incidents of potential iatrogenic exposure to CJD via surgery: 2000 to 30 June 2011.
A surgical incident occurs when a patient with or at increased risk of CJD has undergone surgery without the appropriate infection control guidance being followed [3]. This could happen if a patient undergoes surgery during the incubation period of CJD, or because information about CJD risk factors is not available at the time of surgery. If this happens, surgical instruments that may be contaminated with the infectious agent that causes CJD, could pose a transmission risk when they are re-used on other patients.
In June 2010 the CJD Incidents Panel changed its protocol for reporting surgical incidents, and a new reporting algorithm was published on the HPA CJD Section website. Under the new protocol only CJD cases (or patients at increased risk of CJD) who have undergone surgical procedures which are thought to pose a possible transmission risk (i.e. within the likely infectious incubation period, and involving medium or high risk procedures) are categorised as ‘surgical incidents'. Other procedures, either earlier in the incubation period, or involving low infectivity tissues, are categorised as ‘CJD Reports'.
Advice has been issued for one surgical incident and twelve CJD reports that have been reported to the CJD Incidents Panel in the first six months of 2011. Table 1 shows the number of CJD surgical incidents reported to the CJD Incidents Panel from 2000 to 30 June 2011 by the diagnosis of the index patient. As shown in the table, 45% of surgical incidents result from surgery on index cases diagnosed with sporadic CJD.
Information about the CJD Incidents Panel can be found on the HPA website [4].
Table 1: CJD surgical incidents (n=437) reported to the CJD Incidents Panel (which have been closed, or where advice has been issued) by diagnosis of index patient: 2000 to 30th June 2011 Index patient status '00 '01 '02 '03 '04 '05 '06 '07 '08 '09 '10 '11 Total incidents (% of total) Total CJD reports
Incid'ts Rep'ts Incid'ts Rep'ts Sporadic (possible, probable or definite) 7 19 22 24 16 18 31 17 21 15 5 4 1 12 196 (45%) 16
vCJD (possible, probable or definite) 6 14 22 5 4 1 2 – 1 – 56 (13%) –
Familial including 'at risk' familial – 2 7 1 3 7 – 2 3 2 – 29 (7%) –
'At risk' vCJD blood component recipient – 4 10 5 1 – 2 – 22 (5%) –
'At risk' - vCJD plasma product recipient – 1 2 – 10 18 9 8 6 9 3 – 66 (15%) –
'At risk' - other – 2 1 2 5 – 1 7 – 20 (5%) –
CJD type unclear/ CJD unlikely 1 – 4 1 2 – 10 (2%) –
Not CJD 2 1 4 7 1 – 3 – 1 – 27 (6%) –
Other – 1 2 1 – 1 – 7 (2%) –
No longer considered 'at-risk' – 1 – 1 – 2 – 4 (1%) –
Total 16 38 56 50 45 56 63 27 33 29 23 4 1 12 437 100% 16
Note: The totals in 2009 and 2010 have changed from those reported in February 2011 as incidents have been closed, or advice has been issued, since the database was archived for the February 2011 report.
If the investigation of a surgical incident identifies any instruments that are considered to be potentially contaminated with the infectious agent, and that could still pose an infection risk to other patients, the Panel advises that these instruments should be removed from general use or refurbished. These instruments may be quarantined, kept for exclusive use on the index patient, refurbished (endoscopes only) or destroyed.
Since 2000 there have been 84 incidents in which instruments have been permanently removed from general use or refurbished (endoscopes only). This is a reduction in the total given in the February 2011 report, as in 2011 the CJD Incidents Panel revised its advice on the re-use of endoscopes that had been through over ten cycles of re-use and decontamination, so that these endoscopes could be returned to general use. This resulted in the Panel revising its advice on endoscopes used in six incidents that were reported in 2010, so that in five of these incidents the Panel advised that none of the instruments involved needed to be removed from general use.
Surgical incidents resulting in ‘at risk’ patients
The Panel may advise contacting and informing patients of their possible exposure to CJD following a surgical incident. These patients should be considered 'at-risk of CJD for public health purposes' and are asked to take certain precautions (i.e. not to donate blood, other tissues or organs, and to inform their medical and dental carers prior to any invasive procedures) in order to reduce the risk of transmitting the CJD agent.
The diagnosis of the index patient; the timing of the procedure relative to the development of clinical CJD; the tissue that instruments were in contact with during the procedure on the index patient; and the number of cycles of re-use and decontamination the instruments have been through following the procedure on the index case – all influence the possible risk to subsequent patients.
The threshold level of risk at which patients are considered to be ‘at increased risk’ of CJD is 1%, in addition to the background risk in the UK population. This risk threshold is based on risk assessment models, using precautionary assumptions. The 1% threshold level is used as a cut off for implementing public health precautions and is not intended to be a precise measure of an individual patient's risk. A similar threshold is used for identifying other patients who have been exposed to possible CJD risks following surgical, blood, plasma and tissue incidents.
From 2000 to 30 June 2011, there have been 25 surgical incidents in which the Panel has advised that 179 patients should be considered to have an increased risk of CJD.
Patient denotifications
Following changes in the assessment of tissue infectivity, the Panel has advised that 38 patients in 14 surgical incidents who were originally considered (and notified) as being ‘at risk' of CJD should no longer be considered ‘at risk', and should be denotified. In November 2005, gastrointestinal endoscopies without invasive procedures were reclassified as low risk procedures, and advice was issued to denotify two patients in one surgical incident. In 2006, anterior eye was reclassified as a ‘medium low' infectivity tissue. This led to a change in advice as only the first patient on whom instruments were used following an anterior eye procedure was to be considered as having an increased risk of CJD. Previously this had applied to the first two patients exposed to such instruments. This resulted in the Panel advising that 16 patients in seven incidents should be denotified. In 2009, the anterior eye was further reclassified as a low infectivity tissue. Following this change, the Panel advised that 20 patients should be denotified.
As of 30 June 2011, the Panel has received confirmation that of the 34 patients originally notified of their exposure (out of the 38 originally considered to be ‘at risk'), 26 patients have been informed that they are no longer considered ‘at risk' and eight patients died before they could be denotified.
Current 'at risk' patients resulting from surgical instruments
There are 12 surgical incidents in which 141 patients are still considered to be at increased risk of CJD. Currently, 119 of these 'at risk' patients have been notified that they are at increased risk of CJD. Local decisions have been taken not to notify four patients in these incidents.
Table 2: Surgical ‘at risk’ patients still identified as being ‘at increased risk of CJD’ by the Panel by procedure on the index patient Diagnosis of index patient Procedure on index patient Number of incidents Patients identified as 'at risk' Patients who died before being notified Local decision not to notify patient Notified patients
Sporadic Brain biopsy 2 28 2 1 25
Variant Appendectomy 1 2 – 2 –
Variant Endoscopy 1 – 1 –
Asymptomatic infected vCJD Endoscopy 1 4 1 – 3
At risk variant Endoscopy 5 36 4 – 32
At risk familial Neurosurgery 1 31 10 – 21
At risk familial Ophthalmic surgery 1 39 1 – 38
Total
12 141 18 4 119
Monitoring of patients 'at increased risk' of CJD
The CJD Incidents Panel and the Advisory Committee on Dangerous Pathogens Transmissible Spongiform Encephalopathy Risk Management Subgroup (formerly the ACDP TSE Working Group) have identified a range of individuals and groups who may have been exposed to an increased risk of CJD as a consequence of their medical care (see table 3 below). The risks of iatrogenic CJD transmission to these different individuals are very uncertain, but potentially devastating. The CJD Incidents Panel has advised that these individuals should be informed of their risk and asked to follow public health precautions to avoid transmitting the infection to others.
It is important to follow up these individuals to help determine the risks of CJD spreading to patients through different routes. Follow up involves a range of activities and is carried out by different organisations. At core, follow up aims to ascertain whether any people who may have been exposed to increased CJD risks go on to develop CJD.
Table 3. Individuals at increased risk of CJD up to 30 June 2011 'At risk' Group Identified as 'at risk' Ever notified as being 'at risk' Alive and Notified Cases Asymptomatic infections
Recipients of blood from vCJD cases 66 27 18 3 1
Blood donors to vCJD cases 112 107 105 –
Other recipients from blood donors to vCJD cases 34 32 30 –
Plasma product recipients (all except one have non-bleeding disorders) 11 10 3 [c] –
Surgical contacts of all CJD cases 141 119 111 –
Highly transfused patients (recipients of blood from =80 donors identified at pre-surgical assessment) 7 6 5 –
Total for at risk groups where HPA holds data 371 301 273 3 1
Patients with bleeding disorders who received UK sourced plasma products [a] 3,840 n/k – 1
Recipients of human derived growth hormone [b] 1,883 Up to 1,883 Up to 1,527 64 –
Total for all 'at risk' groups [d] 6094 At least 2184 At least 1800 67 2
a. Data provided by the UK Haemophilia Centre Doctors' Organisation (UKHCDO). These are minimum figures. Central reporting for bleeding disorder patients is incomplete, and some patients have opted out of the central UKHCDO database. Individual haemophilia centres were asked to send out standardised letters of notification to all their ‘at risk’ patients, but the exact number of patients who received these letters and are therefore aware of their risk is not known. b. Data provided by the Institute for Child Health. A small number of ‘at risk' growth hormone recipients are not included in the Institute of Child Health study so the true number ‘at risk’ will be greater. The exact number of growth hormone recipients in the ICH study currently aware of their risk is not known, as given their age at the original notification many were informed indirectly, by their parents. c. The current status for one plasma ‘at risk' patient is under review by Health Protection Scotland. d. These are minimum figures given the comments made above.
Six-monthly update on the National Anonymous Tonsil Archive: end of July 2011
The National Anonymous Tonsil Archive (NATA) was set up in 2004 to prospectively collect 100,000 tonsils pairs obtained after routine tonsillectomies in England and Scotland and to test these samples for abnormal prion protein. Only tissue not required for patient care, which would normally be discarded, is collected. Tonsils are tested for abnormal prion protein by two commercial enzyme immunoassays (EIAs), and a small proportion selected for other analytical tests. Initial results from analysis of 63,007 of the tonsil samples, indicated that all tonsils were negative so far for the detection of PrPCJD protein [5].
Up to the end of July 2011, NATA has received a total of 94,611 tonsil pairs from hospitals in England and Scotland, about 17,849 of which are from the birth cohort in which most vCJD cases have arisen (1961-1985). A further 3,000 tonsil pairs have been received from the Medical Research Council Prion Unit at the UCL Institute for Neurology, National Hospital for Neurology and Neurosurgery. Therefore the total number of tonsil pairs in the archive as at the end of July 2011 was 96,949. The number of collection forms that were completed but where no tonsil tissue was collected was 2,541 (1,663 due to patient objection and 878 due to clinical pathology being requested).
Of the 100 NHS Hospital Trusts that perform over 200 tonsillectomies per year in England, 91 have been recruited and are currently sending tonsil pairs to NATA on a regular basis. There are 120 hospital sites within these trusts taking part in NATA. At present, approximately 50,000 tonsillectomies are performed annually in England. Figure 4 shows the number of tonsil pairs received from each Strategic Health Authority area.
Figure 1. Number of tonsil pairs collected for NATA quarterly (Q1, 2004 to Q3, 2011)
Figure 2. Tonsils pairs collected by Strategic Health Authority (January 2004 to July 2011)
Figure 3. NHS Trusts and Scottish hospitals currently collecting and sending tonsil tissue to the archive July 2011
References
1. The National Creutzfeldt-Jakob Disease Research and Surveillance Unit, The University of Edinburgh. CJD statistics. Available at: http://www.cjd.ed.ac.uk/figures.htm.
2. The National Creutzfeldt-Jakob Disease Research and Surveillance Unit, The University of Edinburgh. Incidence of variant Creutzfeldt-Jakob disease onsets and deaths in the UK January 1994 - May 2011. Edinburgh: NCJDSU, 18 May 2011. Available at: http://www.cjd.ed.ac.uk/cjdq68.pdf.
3. Transmissible spongiform encephalopathy agents: safe working and the prevention of infection. The ACDP TSE Risk Management Subgroup. http://www.dh.gov.uk/ab/ACDP/TSEguidance/index.htm.
4. HPA CJD Incidents Panel [online]. Available at: http://www.hpa.org.uk/web/ CJDIncidentsPanel.
5. Clewley J, Kelly CM, Andrews N, Vogliqi K, Mallinson G, Kaisar M, et al. Prevalence of disease related prion protein in anonymous tonsil specimens in Britain: cross sectional opportunistic survey. BMJ 2009; 338: b1442.
http://www.hpa.org.uk/hpr/infections/ei_cjd.htm
2008
POSITION STATEMENT PREVALENCE OF SUBCLINICAL VARIANT CREUTZFELDT-JAKOB DISEASE INFECTIONS
http://webarchive.nationalarchives.gov.uk/20110316162913/http://www.seac.gov.uk/statements/state-cjd-infections.pdf
2009
BMJ 2009; 338:b1442 doi: 10.1136/bmj.b1442 (Published 21 May 2009) Cite this as: BMJ 2009; 338:b1442 Research
Prevalence of disease related prion protein in anonymous tonsil specimens in Britain: cross sectional opportunistic survey
Jonathan P Clewley, clinical scientist1, Carole M Kelly, research epidemiologist1, Nick Andrews, statistician1, Kelly Vogliqi, research technician1, Gary Mallinson, clinical scientist2, Maria Kaisar, research scientist2, David A Hilton, consultant neuropathologist3, James W Ironside, professor of clinical neuropathology4, Philip Edwards, biomedical scientist3, Linda M McCardle, biomedical scientist4, Diane L Ritchie, research assistant4, Reza Dabaghian, research scientist1, Helen E Ambrose, research scientist1, O Noel Gill, consultant epidemiologist1
+ Author Affiliations
1Centre for Infections, Health Protection Agency, London NW9 5EQ
2Bristol Institute for Transfusion Sciences, National Blood Service, Bristol BS10 5ND
3Department of Histopathology, Derriford Hospital, Plymouth PL6 8DH
4National CJD Surveillance Unit, University of Edinburgh, Western General Hospital, Edinburgh EH4 2XU
Correspondence to: JP Clewley jonathan.clewley@hpa.org.uk Accepted 15 December 2008
Abstract
Objective
To establish with improved accuracy the prevalence of disease related prion protein (PrPCJD) in the population of Britain and thereby guide a proportionate public health response to limit the threat of healthcare associated transmission of variant Creutzfeldt-Jakob disease (vCJD).
Design Cross sectional opportunistic survey.
Study samples Anonymised tonsil pairs removed at elective tonsillectomy throughout England and Scotland.
Setting National anonymous tissue archive for England and Scotland.
Main outcome measure Presence of PrPCJD determined by using two enzyme immunoassays based on different analytical principles, with further investigation by immunohistochemistry or immunoblotting of any samples reactive in either assay.
Results Testing of 63007 samples was completed by the end of September 2008. Of these, 12753 were from the birth cohort in which most vCJD cases have arisen (1961-85) and 19908 were from the 1986-95 cohort that would have been also exposed to bovine spongiform encephalopathy through infected meat or meat products. None of the samples tested was unequivocally reactive in both enzyme immunoassays.
Only two samples were reactive in one or other enzyme immunoassay and equivocal in the other, and nine samples were equivocally reactive in both enzyme immunoassays.
Two hundred and seventy six samples were initially reactive in one or other enzyme immunoassay; the repeat reactivity rate was 15% or less, depending on the enzyme immunoassay and cut-off definition. None of the samples (including all the 276 initially reactive in enzyme immunoassay) that were investigated by immunohistochemistry or immunoblotting was positive for the presence of PrPCJD.
Conclusions The observed prevalence of PrPCJD in tonsils from the 1961-95 combined birth cohort was 0/32661 with a 95% confidence interval of 0 to 113 per million. In the 1961-85 cohort, the prevalence of zero with a 95% confidence interval of 0 to 289 per million was lower than, but still consistent with, a previous survey of appendix tissue that showed a prevalence of 292 per million with a 95% confidence interval of 60 to 853 per million. Continuing to archive and test tonsil specimens, especially in older birth cohorts, and other complementary large scale anonymous tissue surveys, particularly of post-mortem tissues, will further refine the calculated prevalence of PrPCJD.
http://www.bmj.com/content/338/bmj.b1442.full.pdf
2010
Large-scale immunohistochemical examination for lymphoreticular prion protein in tonsil specimens collected in Britain†
Mar Fernandez de Marco1, Jacqueline Linehan2, O Noel Gill3, Jonathan P Clewley3,*, Sebastian Brandner1,*Article first published online: 4 OCT 2010
DOI: 10.1002/path.2767
Keywords:variant Creutzfeldt–Jakob disease;bovine spongiform encephalopathy;vCJD prevalence;PrP
Abstract
There have been 173 cases of variant Creutzfeldt–Jakob disease (vCJD) in the UK, as of 5 July 2010, as a result of the bovine spongiform encephalopathy epidemic. The number of individuals subclinically infected with vCJD, and thus the eventual number of cases, remains, however, uncertain. In an attempt to address this problem, 63 007 tonsil tissue specimens were previously tested by enzyme immunoassay (EIA) for the presence of disease-related prion protein (PrPres) and found to be negative. To confirm the reliability of this result, all those in the birth cohort most at risk (1961–1985) and a few others, including controls, have now been tested by immunohistochemistry (IHC). Histological slides were prepared from 10 075 anonymized formalin-fixed, paraffin-embedded tissues and examined for PrPres with two anti-prion protein antibodies, ICMS35 and KG9. One specimen showed a single strongly positive follicle with both antibodies, on two slides from adjacent sections. As this specimen was negative when it was further investigated by EIA, IHC, and immunoblotting, it is unclear whether the patient from whom the tonsil came will go on to develop vCJD. If, however, this is the case, then a finding of 1 out of 9160 gives a prevalence of disease-related prion protein in the British population of 109 per million, with a 95% confidence interval (CI) of 3–608 per million, which is not statistically different (exact p = 0.63) from population prevalence estimates based on finding three positives out of 10 278 in a previous IHC study of appendix tissue. If this is not the case, a finding of 0 out of 9160 gives a prevalence of 0–403 per million (95% CI) for the 1961-1985 cohort, which is also not different (exact p = 0.25) from previous population prevalence estimates. Therefore, the results of this work could be summarized as finding, by IHC, no or one vCJD-positive individual.
Copyright © 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
http://onlinelibrary.wiley.com/doi/10.1002/path.2767/abstract
snip...
Discussion
Of the 9675 samples for which an IHC result was obtained, 9160 were in the 1961–1985 birth cohort. The remainder of the samples were selected for IHC because they showed some reactivity in the original serological screening of the 63 007 tonsils by EIA with Bio-Rad and Microsens kits [6]. In addition, there were three positive controls (sheep scrapie) among the 9675 samples submitted for IHC. Three samples (18 864, 38 660, and 40 751) gave IHC results that needed to be investigated more fully. Two of these IHC results were concluded to be background staining by three experts, while for the third it was concluded that there was one strongly positive follicle with both KG9 and ICSM35 antibodies. This could not be confirmed by analysis of slides made from further tissue samples embedded in wax, neither could it be confirmed by IB. This result raises the question of the significance and interpretation of a single positive follicle among the thousands from several sections that were examined, particularly in the light of the failure of IB to confirm the presence of PrPCJD in the tissue. Further investigation of tissue from this specimen by bioassay or protein misfolding cyclic amplification (PMCA) was considered not to be worthwhile because bioassay is unlikely to be more sensitive than enhanced chemiluminescent IB tests [11,25,27,28] and PMCA is insufficiently robust [29].
Our finding of one PrPres-positive follicle by IHC can be interpreted as showing that there is one individual in the 9160 samples from the 1961–1985 birth cohort who will go on to develop vCJD. Alternatively, if a single positive follicle is indicative of an insufficient amount of PrPres to spread and cause disease, the interpretation is that there is no one in the 9160 samples from the 1961–1985 birth cohort who will go on to develop vCJD. The decision between these two interpretations needs to be considered in the context of the relative sensitivities of the different tests that were used, and also in the context of the pathological significance of a small quantity of PrPres in a tonsil. Although all three methods (EIA, IB, and IHC) are based on the recognition of PrPres by specific anti- PrP antibodies, they are qualitatively and quantitatively different. As just a few stained cells can be seen by IHC, it could be argued that it is the more sensitive technique. Conversely, however, as a greater volume of tissue and therefore a larger number of cells can be tested by EIA and IB, it can be argued that they are the more sensitive methods [15]. However, the distribution of PrPres in the tissue is likely to be an important factor in assessing the comparative sensitivities of different tests: when there is a very focal deposition of PrPres, IHC may be assumed to have the advantage.
Therefore, while we cannot say whether the patient from whom this tissue came will go on to develop vCJD, we can be reasonably certain, however, that the patient has not yet developed disease as the codon 129 PRNP genotype is MV, and all probable and definite vCJD cases to date have been MM at this loci. There have been four ‘possible’ cases of clinical vCJD, one of which was MV, but this was not biochemically confirmed and it was in a different birth cohort from the person from whom the tonsil in our study came [30]. Also, the two IHC positives (out of three) from the previous study [26] for which a codon 129 genotype could be determined were PRNP codon 129VV [31] and no vCJD cases of this genotype have been reported.
The prevalence in the British population of underlying disease-related prion protein calculated from these findings is, if specimen 38 660 came from a vCJDpositive person, 109 per million for the 1961–1985 birth cohort, with a 95% confidence interval (CI) of 3–608 per million (Table 2), which is not different (exact p = 0.63) to the finding of three positives from 10 278 samples for the appendix survey [26]. If tonsil 38 660 did not come from a vCJD-positive person, then the prevalence is 0 per million with an upper 95% CI of 403 for the 1961–1985 cohort and 0 per million for the 1961–1995 cohort with an upper 95% CI of 394 (Table 2), which is not different (exact p = 0.25) from the previous study.
It is possible that infection arising from exposure to BSE could cause more than one type of prion disease [32–34]. Strains other than that resulting in vCJD, if they exist, may have markedly different pathogenesis, tissue distributions, and structural forms of PrPres. In addition, it is possible that genetic variability in the population may alter the pathogenesis of vCJD, in that the timing and rate of PrPres in appendix and tonsil tissues may differ between individuals. Indeed, genetic differences may even determine the extent of lymphoreticular pathogenesis [31].
Given that the collection of tonsils in our study has occurred later than the collection of appendix samples in the earlier appendix survey, it is conceivable that tonsils have been collected from infected individuals further into the incubation period than is the case for those individuals whose appendices were tested in the earlier survey [26]. Moreover, should the incubation period for prion disease be considerably longer in people with different genotypes, uncertainty about the timing of the appearance of detectable PrPres in these will increase, with concomitant implications for the interpretation of results of PrPres prevalence surveys [6].
Animal experiments have shown that high infectivity, and even disease, can be present in the absence of detectable PrPres [35]. However, this observation cannot be generalized, as PrPres has always been detectable in the lymphoid tissues that have been tested from vCJD patients [6,25,28]. Data from animal experiments also show ‘clearance’ of PrPres after inoculation [35,36]. Therefore, the PrPres found in the earlier survey of appendix tissue [26] may conceivably have been transient and eventually cleared without resulting in clinical disease, and therefore the result of the appendix survey result may not be replicable by the current tonsil survey [6].
Although, statistically, the vCJD prevalence estimates in this work do not differ significantly from those obtained by calculating from the previous Hilton study [26], qualitatively they suggest that prevalence estimates may be cautiously lowered. However, in an attempt to provide statistically significant evidence to demonstrate this, a large-scale IHC survey of recently collected appendix tissue specimens for the presence of PrPres is underway.
SEE FULL TEXT PDF ;
http://onlinelibrary.wiley.com/doi/10.1002/path.2767/pdf
Wednesday, June 29, 2011
TSEAC Meeting August 1, 2011 donor deferral Saudi Arabia vCJD risk blood and blood products
http://tseac.blogspot.com/2011/06/tseac-meeting-august-1-2011-donor.html
Saturday, April 30, 2011
Blood product, collected from a donor who was at risk for variant Creutzfeldt-Jakob disease (vCJD), was distributed APRIL 27, 2011
http://vcjdtransfusion.blogspot.com/2011/04/blood-product-collected-from-donor-who.html
Tuesday, December 14, 2010
Infection control of CJD, vCJD and other human prion diseases in healthcare and community settings part 4, Annex A1, Annex J, UPDATE DECEMBER 2010
http://creutzfeldt-jakob-disease.blogspot.com/2010/12/infection-control-of-cjd-vcjd-and-other.html
grinding bone ???
Monday, January 17, 2011
Aerosols Transmit Prions to Immunocompetent and Immunodeficient Mice
http://transmissiblespongiformencephalopathy.blogspot.com/2011/01/aerosols-transmit-prions-to.html
Tuesday, August 12, 2008
Biosafety in Microbiological and Biomedical Laboratories Fifth Edition 2007 (occupational exposure to prion diseases)
http://creutzfeldt-jakob-disease.blogspot.com/2008/08/biosafety-in-microbiological-and.html
High CJD infectivity remains after prion protein is destroyed
Kohtaro Miyazawa, Kaitlin Emmerling,
Laura Manuelidis DOI: 10.1002/jcb.23286
Copyright © 2011 Wiley-Liss, Inc.
Keywords: proteinase K; keratinase; Transmissible Spongiform Encephalopathies; scrapie; infectious particles; agent strains; cell culture
Abstract
The hypothesis that host prion protein (PrP) converts into an infectious prion form rests on the observation that infectivity progressively decreases in direct proportion to the decrease of PrP with proteinase K (PK) treatment. PrP that resists limited PK digestion (PrP-res, PrPsc) has been assumed to be the infectious form, with speculative types of misfolding encoding the many unique TSE agent strains. Recently, a PK sensitive form of PrP has been proposed as the prion. Thus we re-evaluated total PrP (sensitive and resistant) and used a cell-based assay for titration of infectious particles. A keratinase (NAP) known to effectively digest PrP was compared to PK. Total PrP in FU-CJD infected brain was reduced to =0.3% in a 2hr PK digest, yet there was no reduction in titer. Remaining non-PrP proteins were easily visualized with colloidal gold in this highly infectious homogenate. In contrast to PK, NAP digestion left 0.8% residual PrP after 2hr, yet decreased titer by >2.5logs; few residual protein bands remained. FU-CJD infected cells with 10x the infectivity of brain by both animal and cell culture assays were also evaluated. NAP again significantly reduced cell infectivity (>3.5 logs). Extreme PK digestions were needed to reduce cell PrP to <0.2%, yet a very high titer of =7.8 logs remained. Our FU-CJD brain results are in good accord with the only other report on maximal PrP digestion and titer. It is likely that one or more residual non-PrP proteins may protect agent nucleic acids in infectious particles. J. Cell. Biochem. © 2011 Wiley-Liss, Inc.
http://onlinelibrary.wiley.com/doi/10.1002/jcb.23286/abstract;jsessionid=96CE34EA74FE3FBC5D3538A7BB5B82A1.d02t03
comment ;
"Host prion protein (PrP) is commonly believed to change into an infectious prion form (PrPsc) that resists proteinase K (PK). This report shows that all forms of PrP can be destroyed with PK, yet huge amounts of the infectious agent survives. Resistant, non-PrP genomic molecules are most likely to encode the transmissible agent strains that incite persistent endemic and epidemic disease."
Laura Manuelidis end...TSS
Saturday, January 16, 2010
Evidence For CJD TSE Transmission Via Endoscopes 1-24-3 re-Singeltary to Bramble et al Evidence For CJD/TSE Transmission Via Endoscopes
http://creutzfeldt-jakob-disease.blogspot.com/2010/01/evidence-for-cjd-tse-transmission-via.html
Tuesday, March 29, 2011
TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY EXPOSURE SPREADING VIA HOSPITALS AND SURGICAL PROCEDURES AROUND THE GLOBE
http://transmissiblespongiformencephalopathy.blogspot.com/2011/03/transmissible-spongiform-encephalopathy.html
Saturday, March 5, 2011
MAD COW ATYPICAL CJD PRION TSE CASES WITH CLASSIFICATIONS PENDING ON THE RISE IN NORTH AMERICA
http://transmissiblespongiformencephalopathy.blogspot.com/2011/03/mad-cow-atypical-cjd-prion-tse-cases.html
Tuesday, April 26, 2011
sporadic CJD RISING Text and figures of the latest annual report of the NCJDRSU covering the period 1990-2009 (published 11th March 2011)
http://creutzfeldt-jakob-disease.blogspot.com/2011/04/sporadic-cjd-rising-text-and-figures-of.html
Thursday, August 4, 2011
Terry Singeltary Sr. on the Creutzfeldt-Jakob Disease Public Health Crisis, Date aired: 27 Jun 2011
http://transmissiblespongiformencephalopathy.blogspot.com/2011/08/terry-singeltary-sr-on-creutzfeldt.html
Saturday, July 23, 2011
CATTLE HEADS WITH TONSILS, BEEF TONGUES, SPINAL CORD, SPECIFIED RISK MATERIALS (SRM's) AND PRIONS, AKA MAD COW DISEASE
http://transmissiblespongiformencephalopathy.blogspot.com/2011/07/cattle-heads-with-tonsils-beef-tongues.html
Saturday, November 6, 2010
TAFS1 Position Paper on Position Paper on Relaxation of the Feed Ban in the EU Berne, 2010 TAFS INTERNATIONAL FORUM FOR TRANSMISSIBLE ANIMAL DISEASES AND FOOD SAFETY a non-profit Swiss Foundation
http://madcowfeed.blogspot.com/2010/11/tafs1-position-paper-on-position-paper.html
Archive Number 20101206.4364 Published Date 06-DEC-2010 Subject PRO/AH/EDR; Prion disease update 2010 (11)
PRION DISEASE UPDATE 2010 (11)
http://www.promedmail.org/pls/apex/f?p=2400:1001:5492868805159684::NO::F2400_P1001_BACK_PAGE,F2400_P1001_PUB_MAIL_ID:1000,86129
Thursday, July 28, 2011
An Update on the Animal Disease Traceability Framework July 27, 2011
http://naiscoolyes.blogspot.com/2011/07/update-on-animal-disease-traceability.html
Saturday, June 25, 2011
Transmissibility of BSE-L and Cattle-Adapted TME Prion Strain to Cynomolgus Macaque
"BSE-L in North America may have existed for decades"
http://transmissiblespongiformencephalopathy.blogspot.com/2011/06/transmissibility-of-bse-l-and-cattle.html
RE - "BSE-L in North America may have existed for decades" YA THINK ???
Over the next 8-10 weeks, approximately 40% of all the adult mink on the farm died from TME.
snip...
The rancher was a ''dead stock'' feeder using mostly (>95%) downer or dead dairy cattle...
http://web.archive.org/web/20030516051623/http://www.bseinquiry.gov.uk/files/mb/m09/tab05.pdf
Sunday, June 26, 2011
Risk Analysis of Low-Dose Prion Exposures in Cynomolgus Macaque
http://transmissiblespongiformencephalopathy.blogspot.com/2011/06/risk-analysis-of-low-dose-prion.html
Thursday, June 23, 2011
Experimental H-type bovine spongiform encephalopathy characterized by plaques and glial- and stellate-type prion protein deposits
http://transmissiblespongiformencephalopathy.blogspot.com/2011/06/experimental-h-type-bovine-spongiform.html
Thursday, July 21, 2011
A Second Case of Gerstmann-Sträussler-Scheinker Disease Linked to the G131V Mutation in the Prion Protein Gene in a Dutch Patient Journal of Neuropathology & Experimental Neurology:
August 2011 - Volume 70 - Issue 8 - pp 698-702
http://transmissiblespongiformencephalopathy.blogspot.com/2011/07/second-case-of-gerstmann-straussler.html
Saturday, August 14, 2010
BSE Case Associated with Prion Protein Gene Mutation (g-h-BSEalabama) and VPSPr PRIONPATHY
(see mad cow feed in COMMERCE IN ALABAMA...TSS)
http://prionpathy.blogspot.com/2010/08/bse-case-associated-with-prion-protein.html
Wednesday, June 15, 2011
Galveston, Texas - Isle port moves through thousands of heifers headed to Russia, none from Texas, Alabama, or Washington, due to BSE risk factor
http://transmissiblespongiformencephalopathy.blogspot.com/2011/06/galveston-texas-isle-port-moves-through.html
TSS
For numbers of CJD case reports, readers should consult data provided by the National CJD Research and Surveillance Unit (NCJDRSU), Edinburgh [1]. The latest yearly analysis of vCJD reports (onsets and deaths) is also available from the NCJDRSU website [2].
Reports of incidents of potential iatrogenic exposure to CJD via surgery: 2000 to 30 June 2011.
A surgical incident occurs when a patient with or at increased risk of CJD has undergone surgery without the appropriate infection control guidance being followed [3]. This could happen if a patient undergoes surgery during the incubation period of CJD, or because information about CJD risk factors is not available at the time of surgery. If this happens, surgical instruments that may be contaminated with the infectious agent that causes CJD, could pose a transmission risk when they are re-used on other patients.
In June 2010 the CJD Incidents Panel changed its protocol for reporting surgical incidents, and a new reporting algorithm was published on the HPA CJD Section website. Under the new protocol only CJD cases (or patients at increased risk of CJD) who have undergone surgical procedures which are thought to pose a possible transmission risk (i.e. within the likely infectious incubation period, and involving medium or high risk procedures) are categorised as ‘surgical incidents'. Other procedures, either earlier in the incubation period, or involving low infectivity tissues, are categorised as ‘CJD Reports'.
Advice has been issued for one surgical incident and twelve CJD reports that have been reported to the CJD Incidents Panel in the first six months of 2011. Table 1 shows the number of CJD surgical incidents reported to the CJD Incidents Panel from 2000 to 30 June 2011 by the diagnosis of the index patient. As shown in the table, 45% of surgical incidents result from surgery on index cases diagnosed with sporadic CJD.
Information about the CJD Incidents Panel can be found on the HPA website [4].
Table 1: CJD surgical incidents (n=437) reported to the CJD Incidents Panel (which have been closed, or where advice has been issued) by diagnosis of index patient: 2000 to 30th June 2011 Index patient status '00 '01 '02 '03 '04 '05 '06 '07 '08 '09 '10 '11 Total incidents (% of total) Total CJD reports
Incid'ts Rep'ts Incid'ts Rep'ts Sporadic (possible, probable or definite) 7 19 22 24 16 18 31 17 21 15 5 4 1 12 196 (45%) 16
vCJD (possible, probable or definite) 6 14 22 5 4 1 2 – 1 – 56 (13%) –
Familial including 'at risk' familial – 2 7 1 3 7 – 2 3 2 – 29 (7%) –
'At risk' vCJD blood component recipient – 4 10 5 1 – 2 – 22 (5%) –
'At risk' - vCJD plasma product recipient – 1 2 – 10 18 9 8 6 9 3 – 66 (15%) –
'At risk' - other – 2 1 2 5 – 1 7 – 20 (5%) –
CJD type unclear/ CJD unlikely 1 – 4 1 2 – 10 (2%) –
Not CJD 2 1 4 7 1 – 3 – 1 – 27 (6%) –
Other – 1 2 1 – 1 – 7 (2%) –
No longer considered 'at-risk' – 1 – 1 – 2 – 4 (1%) –
Total 16 38 56 50 45 56 63 27 33 29 23 4 1 12 437 100% 16
Note: The totals in 2009 and 2010 have changed from those reported in February 2011 as incidents have been closed, or advice has been issued, since the database was archived for the February 2011 report.
If the investigation of a surgical incident identifies any instruments that are considered to be potentially contaminated with the infectious agent, and that could still pose an infection risk to other patients, the Panel advises that these instruments should be removed from general use or refurbished. These instruments may be quarantined, kept for exclusive use on the index patient, refurbished (endoscopes only) or destroyed.
Since 2000 there have been 84 incidents in which instruments have been permanently removed from general use or refurbished (endoscopes only). This is a reduction in the total given in the February 2011 report, as in 2011 the CJD Incidents Panel revised its advice on the re-use of endoscopes that had been through over ten cycles of re-use and decontamination, so that these endoscopes could be returned to general use. This resulted in the Panel revising its advice on endoscopes used in six incidents that were reported in 2010, so that in five of these incidents the Panel advised that none of the instruments involved needed to be removed from general use.
Surgical incidents resulting in ‘at risk’ patients
The Panel may advise contacting and informing patients of their possible exposure to CJD following a surgical incident. These patients should be considered 'at-risk of CJD for public health purposes' and are asked to take certain precautions (i.e. not to donate blood, other tissues or organs, and to inform their medical and dental carers prior to any invasive procedures) in order to reduce the risk of transmitting the CJD agent.
The diagnosis of the index patient; the timing of the procedure relative to the development of clinical CJD; the tissue that instruments were in contact with during the procedure on the index patient; and the number of cycles of re-use and decontamination the instruments have been through following the procedure on the index case – all influence the possible risk to subsequent patients.
The threshold level of risk at which patients are considered to be ‘at increased risk’ of CJD is 1%, in addition to the background risk in the UK population. This risk threshold is based on risk assessment models, using precautionary assumptions. The 1% threshold level is used as a cut off for implementing public health precautions and is not intended to be a precise measure of an individual patient's risk. A similar threshold is used for identifying other patients who have been exposed to possible CJD risks following surgical, blood, plasma and tissue incidents.
From 2000 to 30 June 2011, there have been 25 surgical incidents in which the Panel has advised that 179 patients should be considered to have an increased risk of CJD.
Patient denotifications
Following changes in the assessment of tissue infectivity, the Panel has advised that 38 patients in 14 surgical incidents who were originally considered (and notified) as being ‘at risk' of CJD should no longer be considered ‘at risk', and should be denotified. In November 2005, gastrointestinal endoscopies without invasive procedures were reclassified as low risk procedures, and advice was issued to denotify two patients in one surgical incident. In 2006, anterior eye was reclassified as a ‘medium low' infectivity tissue. This led to a change in advice as only the first patient on whom instruments were used following an anterior eye procedure was to be considered as having an increased risk of CJD. Previously this had applied to the first two patients exposed to such instruments. This resulted in the Panel advising that 16 patients in seven incidents should be denotified. In 2009, the anterior eye was further reclassified as a low infectivity tissue. Following this change, the Panel advised that 20 patients should be denotified.
As of 30 June 2011, the Panel has received confirmation that of the 34 patients originally notified of their exposure (out of the 38 originally considered to be ‘at risk'), 26 patients have been informed that they are no longer considered ‘at risk' and eight patients died before they could be denotified.
Current 'at risk' patients resulting from surgical instruments
There are 12 surgical incidents in which 141 patients are still considered to be at increased risk of CJD. Currently, 119 of these 'at risk' patients have been notified that they are at increased risk of CJD. Local decisions have been taken not to notify four patients in these incidents.
Table 2: Surgical ‘at risk’ patients still identified as being ‘at increased risk of CJD’ by the Panel by procedure on the index patient Diagnosis of index patient Procedure on index patient Number of incidents Patients identified as 'at risk' Patients who died before being notified Local decision not to notify patient Notified patients
Sporadic Brain biopsy 2 28 2 1 25
Variant Appendectomy 1 2 – 2 –
Variant Endoscopy 1 – 1 –
Asymptomatic infected vCJD Endoscopy 1 4 1 – 3
At risk variant Endoscopy 5 36 4 – 32
At risk familial Neurosurgery 1 31 10 – 21
At risk familial Ophthalmic surgery 1 39 1 – 38
Total
12 141 18 4 119
Monitoring of patients 'at increased risk' of CJD
The CJD Incidents Panel and the Advisory Committee on Dangerous Pathogens Transmissible Spongiform Encephalopathy Risk Management Subgroup (formerly the ACDP TSE Working Group) have identified a range of individuals and groups who may have been exposed to an increased risk of CJD as a consequence of their medical care (see table 3 below). The risks of iatrogenic CJD transmission to these different individuals are very uncertain, but potentially devastating. The CJD Incidents Panel has advised that these individuals should be informed of their risk and asked to follow public health precautions to avoid transmitting the infection to others.
It is important to follow up these individuals to help determine the risks of CJD spreading to patients through different routes. Follow up involves a range of activities and is carried out by different organisations. At core, follow up aims to ascertain whether any people who may have been exposed to increased CJD risks go on to develop CJD.
Table 3. Individuals at increased risk of CJD up to 30 June 2011 'At risk' Group Identified as 'at risk' Ever notified as being 'at risk' Alive and Notified Cases Asymptomatic infections
Recipients of blood from vCJD cases 66 27 18 3 1
Blood donors to vCJD cases 112 107 105 –
Other recipients from blood donors to vCJD cases 34 32 30 –
Plasma product recipients (all except one have non-bleeding disorders) 11 10 3 [c] –
Surgical contacts of all CJD cases 141 119 111 –
Highly transfused patients (recipients of blood from =80 donors identified at pre-surgical assessment) 7 6 5 –
Total for at risk groups where HPA holds data 371 301 273 3 1
Patients with bleeding disorders who received UK sourced plasma products [a] 3,840 n/k – 1
Recipients of human derived growth hormone [b] 1,883 Up to 1,883 Up to 1,527 64 –
Total for all 'at risk' groups [d] 6094 At least 2184 At least 1800 67 2
a. Data provided by the UK Haemophilia Centre Doctors' Organisation (UKHCDO). These are minimum figures. Central reporting for bleeding disorder patients is incomplete, and some patients have opted out of the central UKHCDO database. Individual haemophilia centres were asked to send out standardised letters of notification to all their ‘at risk’ patients, but the exact number of patients who received these letters and are therefore aware of their risk is not known. b. Data provided by the Institute for Child Health. A small number of ‘at risk' growth hormone recipients are not included in the Institute of Child Health study so the true number ‘at risk’ will be greater. The exact number of growth hormone recipients in the ICH study currently aware of their risk is not known, as given their age at the original notification many were informed indirectly, by their parents. c. The current status for one plasma ‘at risk' patient is under review by Health Protection Scotland. d. These are minimum figures given the comments made above.
Six-monthly update on the National Anonymous Tonsil Archive: end of July 2011
The National Anonymous Tonsil Archive (NATA) was set up in 2004 to prospectively collect 100,000 tonsils pairs obtained after routine tonsillectomies in England and Scotland and to test these samples for abnormal prion protein. Only tissue not required for patient care, which would normally be discarded, is collected. Tonsils are tested for abnormal prion protein by two commercial enzyme immunoassays (EIAs), and a small proportion selected for other analytical tests. Initial results from analysis of 63,007 of the tonsil samples, indicated that all tonsils were negative so far for the detection of PrPCJD protein [5].
Up to the end of July 2011, NATA has received a total of 94,611 tonsil pairs from hospitals in England and Scotland, about 17,849 of which are from the birth cohort in which most vCJD cases have arisen (1961-1985). A further 3,000 tonsil pairs have been received from the Medical Research Council Prion Unit at the UCL Institute for Neurology, National Hospital for Neurology and Neurosurgery. Therefore the total number of tonsil pairs in the archive as at the end of July 2011 was 96,949. The number of collection forms that were completed but where no tonsil tissue was collected was 2,541 (1,663 due to patient objection and 878 due to clinical pathology being requested).
Of the 100 NHS Hospital Trusts that perform over 200 tonsillectomies per year in England, 91 have been recruited and are currently sending tonsil pairs to NATA on a regular basis. There are 120 hospital sites within these trusts taking part in NATA. At present, approximately 50,000 tonsillectomies are performed annually in England. Figure 4 shows the number of tonsil pairs received from each Strategic Health Authority area.
Figure 1. Number of tonsil pairs collected for NATA quarterly (Q1, 2004 to Q3, 2011)
Figure 2. Tonsils pairs collected by Strategic Health Authority (January 2004 to July 2011)
Figure 3. NHS Trusts and Scottish hospitals currently collecting and sending tonsil tissue to the archive July 2011
References
1. The National Creutzfeldt-Jakob Disease Research and Surveillance Unit, The University of Edinburgh. CJD statistics. Available at: http://www.cjd.ed.ac.uk/figures.htm.
2. The National Creutzfeldt-Jakob Disease Research and Surveillance Unit, The University of Edinburgh. Incidence of variant Creutzfeldt-Jakob disease onsets and deaths in the UK January 1994 - May 2011. Edinburgh: NCJDSU, 18 May 2011. Available at: http://www.cjd.ed.ac.uk/cjdq68.pdf.
3. Transmissible spongiform encephalopathy agents: safe working and the prevention of infection. The ACDP TSE Risk Management Subgroup. http://www.dh.gov.uk/ab/ACDP/TSEguidance/index.htm.
4. HPA CJD Incidents Panel [online]. Available at: http://www.hpa.org.uk/web/ CJDIncidentsPanel.
5. Clewley J, Kelly CM, Andrews N, Vogliqi K, Mallinson G, Kaisar M, et al. Prevalence of disease related prion protein in anonymous tonsil specimens in Britain: cross sectional opportunistic survey. BMJ 2009; 338: b1442.
http://www.hpa.org.uk/hpr/infections/ei_cjd.htm
2008
POSITION STATEMENT PREVALENCE OF SUBCLINICAL VARIANT CREUTZFELDT-JAKOB DISEASE INFECTIONS
http://webarchive.nationalarchives.gov.uk/20110316162913/http://www.seac.gov.uk/statements/state-cjd-infections.pdf
2009
BMJ 2009; 338:b1442 doi: 10.1136/bmj.b1442 (Published 21 May 2009) Cite this as: BMJ 2009; 338:b1442 Research
Prevalence of disease related prion protein in anonymous tonsil specimens in Britain: cross sectional opportunistic survey
Jonathan P Clewley, clinical scientist1, Carole M Kelly, research epidemiologist1, Nick Andrews, statistician1, Kelly Vogliqi, research technician1, Gary Mallinson, clinical scientist2, Maria Kaisar, research scientist2, David A Hilton, consultant neuropathologist3, James W Ironside, professor of clinical neuropathology4, Philip Edwards, biomedical scientist3, Linda M McCardle, biomedical scientist4, Diane L Ritchie, research assistant4, Reza Dabaghian, research scientist1, Helen E Ambrose, research scientist1, O Noel Gill, consultant epidemiologist1
+ Author Affiliations
1Centre for Infections, Health Protection Agency, London NW9 5EQ
2Bristol Institute for Transfusion Sciences, National Blood Service, Bristol BS10 5ND
3Department of Histopathology, Derriford Hospital, Plymouth PL6 8DH
4National CJD Surveillance Unit, University of Edinburgh, Western General Hospital, Edinburgh EH4 2XU
Correspondence to: JP Clewley jonathan.clewley@hpa.org.uk Accepted 15 December 2008
Abstract
Objective
To establish with improved accuracy the prevalence of disease related prion protein (PrPCJD) in the population of Britain and thereby guide a proportionate public health response to limit the threat of healthcare associated transmission of variant Creutzfeldt-Jakob disease (vCJD).
Design Cross sectional opportunistic survey.
Study samples Anonymised tonsil pairs removed at elective tonsillectomy throughout England and Scotland.
Setting National anonymous tissue archive for England and Scotland.
Main outcome measure Presence of PrPCJD determined by using two enzyme immunoassays based on different analytical principles, with further investigation by immunohistochemistry or immunoblotting of any samples reactive in either assay.
Results Testing of 63007 samples was completed by the end of September 2008. Of these, 12753 were from the birth cohort in which most vCJD cases have arisen (1961-85) and 19908 were from the 1986-95 cohort that would have been also exposed to bovine spongiform encephalopathy through infected meat or meat products. None of the samples tested was unequivocally reactive in both enzyme immunoassays.
Only two samples were reactive in one or other enzyme immunoassay and equivocal in the other, and nine samples were equivocally reactive in both enzyme immunoassays.
Two hundred and seventy six samples were initially reactive in one or other enzyme immunoassay; the repeat reactivity rate was 15% or less, depending on the enzyme immunoassay and cut-off definition. None of the samples (including all the 276 initially reactive in enzyme immunoassay) that were investigated by immunohistochemistry or immunoblotting was positive for the presence of PrPCJD.
Conclusions The observed prevalence of PrPCJD in tonsils from the 1961-95 combined birth cohort was 0/32661 with a 95% confidence interval of 0 to 113 per million. In the 1961-85 cohort, the prevalence of zero with a 95% confidence interval of 0 to 289 per million was lower than, but still consistent with, a previous survey of appendix tissue that showed a prevalence of 292 per million with a 95% confidence interval of 60 to 853 per million. Continuing to archive and test tonsil specimens, especially in older birth cohorts, and other complementary large scale anonymous tissue surveys, particularly of post-mortem tissues, will further refine the calculated prevalence of PrPCJD.
http://www.bmj.com/content/338/bmj.b1442.full.pdf
2010
Large-scale immunohistochemical examination for lymphoreticular prion protein in tonsil specimens collected in Britain†
Mar Fernandez de Marco1, Jacqueline Linehan2, O Noel Gill3, Jonathan P Clewley3,*, Sebastian Brandner1,*Article first published online: 4 OCT 2010
DOI: 10.1002/path.2767
Keywords:variant Creutzfeldt–Jakob disease;bovine spongiform encephalopathy;vCJD prevalence;PrP
Abstract
There have been 173 cases of variant Creutzfeldt–Jakob disease (vCJD) in the UK, as of 5 July 2010, as a result of the bovine spongiform encephalopathy epidemic. The number of individuals subclinically infected with vCJD, and thus the eventual number of cases, remains, however, uncertain. In an attempt to address this problem, 63 007 tonsil tissue specimens were previously tested by enzyme immunoassay (EIA) for the presence of disease-related prion protein (PrPres) and found to be negative. To confirm the reliability of this result, all those in the birth cohort most at risk (1961–1985) and a few others, including controls, have now been tested by immunohistochemistry (IHC). Histological slides were prepared from 10 075 anonymized formalin-fixed, paraffin-embedded tissues and examined for PrPres with two anti-prion protein antibodies, ICMS35 and KG9. One specimen showed a single strongly positive follicle with both antibodies, on two slides from adjacent sections. As this specimen was negative when it was further investigated by EIA, IHC, and immunoblotting, it is unclear whether the patient from whom the tonsil came will go on to develop vCJD. If, however, this is the case, then a finding of 1 out of 9160 gives a prevalence of disease-related prion protein in the British population of 109 per million, with a 95% confidence interval (CI) of 3–608 per million, which is not statistically different (exact p = 0.63) from population prevalence estimates based on finding three positives out of 10 278 in a previous IHC study of appendix tissue. If this is not the case, a finding of 0 out of 9160 gives a prevalence of 0–403 per million (95% CI) for the 1961-1985 cohort, which is also not different (exact p = 0.25) from previous population prevalence estimates. Therefore, the results of this work could be summarized as finding, by IHC, no or one vCJD-positive individual.
Copyright © 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
http://onlinelibrary.wiley.com/doi/10.1002/path.2767/abstract
snip...
Discussion
Of the 9675 samples for which an IHC result was obtained, 9160 were in the 1961–1985 birth cohort. The remainder of the samples were selected for IHC because they showed some reactivity in the original serological screening of the 63 007 tonsils by EIA with Bio-Rad and Microsens kits [6]. In addition, there were three positive controls (sheep scrapie) among the 9675 samples submitted for IHC. Three samples (18 864, 38 660, and 40 751) gave IHC results that needed to be investigated more fully. Two of these IHC results were concluded to be background staining by three experts, while for the third it was concluded that there was one strongly positive follicle with both KG9 and ICSM35 antibodies. This could not be confirmed by analysis of slides made from further tissue samples embedded in wax, neither could it be confirmed by IB. This result raises the question of the significance and interpretation of a single positive follicle among the thousands from several sections that were examined, particularly in the light of the failure of IB to confirm the presence of PrPCJD in the tissue. Further investigation of tissue from this specimen by bioassay or protein misfolding cyclic amplification (PMCA) was considered not to be worthwhile because bioassay is unlikely to be more sensitive than enhanced chemiluminescent IB tests [11,25,27,28] and PMCA is insufficiently robust [29].
Our finding of one PrPres-positive follicle by IHC can be interpreted as showing that there is one individual in the 9160 samples from the 1961–1985 birth cohort who will go on to develop vCJD. Alternatively, if a single positive follicle is indicative of an insufficient amount of PrPres to spread and cause disease, the interpretation is that there is no one in the 9160 samples from the 1961–1985 birth cohort who will go on to develop vCJD. The decision between these two interpretations needs to be considered in the context of the relative sensitivities of the different tests that were used, and also in the context of the pathological significance of a small quantity of PrPres in a tonsil. Although all three methods (EIA, IB, and IHC) are based on the recognition of PrPres by specific anti- PrP antibodies, they are qualitatively and quantitatively different. As just a few stained cells can be seen by IHC, it could be argued that it is the more sensitive technique. Conversely, however, as a greater volume of tissue and therefore a larger number of cells can be tested by EIA and IB, it can be argued that they are the more sensitive methods [15]. However, the distribution of PrPres in the tissue is likely to be an important factor in assessing the comparative sensitivities of different tests: when there is a very focal deposition of PrPres, IHC may be assumed to have the advantage.
Therefore, while we cannot say whether the patient from whom this tissue came will go on to develop vCJD, we can be reasonably certain, however, that the patient has not yet developed disease as the codon 129 PRNP genotype is MV, and all probable and definite vCJD cases to date have been MM at this loci. There have been four ‘possible’ cases of clinical vCJD, one of which was MV, but this was not biochemically confirmed and it was in a different birth cohort from the person from whom the tonsil in our study came [30]. Also, the two IHC positives (out of three) from the previous study [26] for which a codon 129 genotype could be determined were PRNP codon 129VV [31] and no vCJD cases of this genotype have been reported.
The prevalence in the British population of underlying disease-related prion protein calculated from these findings is, if specimen 38 660 came from a vCJDpositive person, 109 per million for the 1961–1985 birth cohort, with a 95% confidence interval (CI) of 3–608 per million (Table 2), which is not different (exact p = 0.63) to the finding of three positives from 10 278 samples for the appendix survey [26]. If tonsil 38 660 did not come from a vCJD-positive person, then the prevalence is 0 per million with an upper 95% CI of 403 for the 1961–1985 cohort and 0 per million for the 1961–1995 cohort with an upper 95% CI of 394 (Table 2), which is not different (exact p = 0.25) from the previous study.
It is possible that infection arising from exposure to BSE could cause more than one type of prion disease [32–34]. Strains other than that resulting in vCJD, if they exist, may have markedly different pathogenesis, tissue distributions, and structural forms of PrPres. In addition, it is possible that genetic variability in the population may alter the pathogenesis of vCJD, in that the timing and rate of PrPres in appendix and tonsil tissues may differ between individuals. Indeed, genetic differences may even determine the extent of lymphoreticular pathogenesis [31].
Given that the collection of tonsils in our study has occurred later than the collection of appendix samples in the earlier appendix survey, it is conceivable that tonsils have been collected from infected individuals further into the incubation period than is the case for those individuals whose appendices were tested in the earlier survey [26]. Moreover, should the incubation period for prion disease be considerably longer in people with different genotypes, uncertainty about the timing of the appearance of detectable PrPres in these will increase, with concomitant implications for the interpretation of results of PrPres prevalence surveys [6].
Animal experiments have shown that high infectivity, and even disease, can be present in the absence of detectable PrPres [35]. However, this observation cannot be generalized, as PrPres has always been detectable in the lymphoid tissues that have been tested from vCJD patients [6,25,28]. Data from animal experiments also show ‘clearance’ of PrPres after inoculation [35,36]. Therefore, the PrPres found in the earlier survey of appendix tissue [26] may conceivably have been transient and eventually cleared without resulting in clinical disease, and therefore the result of the appendix survey result may not be replicable by the current tonsil survey [6].
Although, statistically, the vCJD prevalence estimates in this work do not differ significantly from those obtained by calculating from the previous Hilton study [26], qualitatively they suggest that prevalence estimates may be cautiously lowered. However, in an attempt to provide statistically significant evidence to demonstrate this, a large-scale IHC survey of recently collected appendix tissue specimens for the presence of PrPres is underway.
SEE FULL TEXT PDF ;
http://onlinelibrary.wiley.com/doi/10.1002/path.2767/pdf
Wednesday, June 29, 2011
TSEAC Meeting August 1, 2011 donor deferral Saudi Arabia vCJD risk blood and blood products
http://tseac.blogspot.com/2011/06/tseac-meeting-august-1-2011-donor.html
Saturday, April 30, 2011
Blood product, collected from a donor who was at risk for variant Creutzfeldt-Jakob disease (vCJD), was distributed APRIL 27, 2011
http://vcjdtransfusion.blogspot.com/2011/04/blood-product-collected-from-donor-who.html
Tuesday, December 14, 2010
Infection control of CJD, vCJD and other human prion diseases in healthcare and community settings part 4, Annex A1, Annex J, UPDATE DECEMBER 2010
http://creutzfeldt-jakob-disease.blogspot.com/2010/12/infection-control-of-cjd-vcjd-and-other.html
grinding bone ???
Monday, January 17, 2011
Aerosols Transmit Prions to Immunocompetent and Immunodeficient Mice
http://transmissiblespongiformencephalopathy.blogspot.com/2011/01/aerosols-transmit-prions-to.html
Tuesday, August 12, 2008
Biosafety in Microbiological and Biomedical Laboratories Fifth Edition 2007 (occupational exposure to prion diseases)
http://creutzfeldt-jakob-disease.blogspot.com/2008/08/biosafety-in-microbiological-and.html
High CJD infectivity remains after prion protein is destroyed
Kohtaro Miyazawa, Kaitlin Emmerling,
Laura Manuelidis DOI: 10.1002/jcb.23286
Copyright © 2011 Wiley-Liss, Inc.
Keywords: proteinase K; keratinase; Transmissible Spongiform Encephalopathies; scrapie; infectious particles; agent strains; cell culture
Abstract
The hypothesis that host prion protein (PrP) converts into an infectious prion form rests on the observation that infectivity progressively decreases in direct proportion to the decrease of PrP with proteinase K (PK) treatment. PrP that resists limited PK digestion (PrP-res, PrPsc) has been assumed to be the infectious form, with speculative types of misfolding encoding the many unique TSE agent strains. Recently, a PK sensitive form of PrP has been proposed as the prion. Thus we re-evaluated total PrP (sensitive and resistant) and used a cell-based assay for titration of infectious particles. A keratinase (NAP) known to effectively digest PrP was compared to PK. Total PrP in FU-CJD infected brain was reduced to =0.3% in a 2hr PK digest, yet there was no reduction in titer. Remaining non-PrP proteins were easily visualized with colloidal gold in this highly infectious homogenate. In contrast to PK, NAP digestion left 0.8% residual PrP after 2hr, yet decreased titer by >2.5logs; few residual protein bands remained. FU-CJD infected cells with 10x the infectivity of brain by both animal and cell culture assays were also evaluated. NAP again significantly reduced cell infectivity (>3.5 logs). Extreme PK digestions were needed to reduce cell PrP to <0.2%, yet a very high titer of =7.8 logs remained. Our FU-CJD brain results are in good accord with the only other report on maximal PrP digestion and titer. It is likely that one or more residual non-PrP proteins may protect agent nucleic acids in infectious particles. J. Cell. Biochem. © 2011 Wiley-Liss, Inc.
http://onlinelibrary.wiley.com/doi/10.1002/jcb.23286/abstract;jsessionid=96CE34EA74FE3FBC5D3538A7BB5B82A1.d02t03
comment ;
"Host prion protein (PrP) is commonly believed to change into an infectious prion form (PrPsc) that resists proteinase K (PK). This report shows that all forms of PrP can be destroyed with PK, yet huge amounts of the infectious agent survives. Resistant, non-PrP genomic molecules are most likely to encode the transmissible agent strains that incite persistent endemic and epidemic disease."
Laura Manuelidis end...TSS
Saturday, January 16, 2010
Evidence For CJD TSE Transmission Via Endoscopes 1-24-3 re-Singeltary to Bramble et al Evidence For CJD/TSE Transmission Via Endoscopes
http://creutzfeldt-jakob-disease.blogspot.com/2010/01/evidence-for-cjd-tse-transmission-via.html
Tuesday, March 29, 2011
TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY EXPOSURE SPREADING VIA HOSPITALS AND SURGICAL PROCEDURES AROUND THE GLOBE
http://transmissiblespongiformencephalopathy.blogspot.com/2011/03/transmissible-spongiform-encephalopathy.html
Saturday, March 5, 2011
MAD COW ATYPICAL CJD PRION TSE CASES WITH CLASSIFICATIONS PENDING ON THE RISE IN NORTH AMERICA
http://transmissiblespongiformencephalopathy.blogspot.com/2011/03/mad-cow-atypical-cjd-prion-tse-cases.html
Tuesday, April 26, 2011
sporadic CJD RISING Text and figures of the latest annual report of the NCJDRSU covering the period 1990-2009 (published 11th March 2011)
http://creutzfeldt-jakob-disease.blogspot.com/2011/04/sporadic-cjd-rising-text-and-figures-of.html
Thursday, August 4, 2011
Terry Singeltary Sr. on the Creutzfeldt-Jakob Disease Public Health Crisis, Date aired: 27 Jun 2011
http://transmissiblespongiformencephalopathy.blogspot.com/2011/08/terry-singeltary-sr-on-creutzfeldt.html
Saturday, July 23, 2011
CATTLE HEADS WITH TONSILS, BEEF TONGUES, SPINAL CORD, SPECIFIED RISK MATERIALS (SRM's) AND PRIONS, AKA MAD COW DISEASE
http://transmissiblespongiformencephalopathy.blogspot.com/2011/07/cattle-heads-with-tonsils-beef-tongues.html
Saturday, November 6, 2010
TAFS1 Position Paper on Position Paper on Relaxation of the Feed Ban in the EU Berne, 2010 TAFS INTERNATIONAL FORUM FOR TRANSMISSIBLE ANIMAL DISEASES AND FOOD SAFETY a non-profit Swiss Foundation
http://madcowfeed.blogspot.com/2010/11/tafs1-position-paper-on-position-paper.html
Archive Number 20101206.4364 Published Date 06-DEC-2010 Subject PRO/AH/EDR; Prion disease update 2010 (11)
PRION DISEASE UPDATE 2010 (11)
http://www.promedmail.org/pls/apex/f?p=2400:1001:5492868805159684::NO::F2400_P1001_BACK_PAGE,F2400_P1001_PUB_MAIL_ID:1000,86129
Thursday, July 28, 2011
An Update on the Animal Disease Traceability Framework July 27, 2011
http://naiscoolyes.blogspot.com/2011/07/update-on-animal-disease-traceability.html
Saturday, June 25, 2011
Transmissibility of BSE-L and Cattle-Adapted TME Prion Strain to Cynomolgus Macaque
"BSE-L in North America may have existed for decades"
http://transmissiblespongiformencephalopathy.blogspot.com/2011/06/transmissibility-of-bse-l-and-cattle.html
RE - "BSE-L in North America may have existed for decades" YA THINK ???
Over the next 8-10 weeks, approximately 40% of all the adult mink on the farm died from TME.
snip...
The rancher was a ''dead stock'' feeder using mostly (>95%) downer or dead dairy cattle...
http://web.archive.org/web/20030516051623/http://www.bseinquiry.gov.uk/files/mb/m09/tab05.pdf
Sunday, June 26, 2011
Risk Analysis of Low-Dose Prion Exposures in Cynomolgus Macaque
http://transmissiblespongiformencephalopathy.blogspot.com/2011/06/risk-analysis-of-low-dose-prion.html
Thursday, June 23, 2011
Experimental H-type bovine spongiform encephalopathy characterized by plaques and glial- and stellate-type prion protein deposits
http://transmissiblespongiformencephalopathy.blogspot.com/2011/06/experimental-h-type-bovine-spongiform.html
Thursday, July 21, 2011
A Second Case of Gerstmann-Sträussler-Scheinker Disease Linked to the G131V Mutation in the Prion Protein Gene in a Dutch Patient Journal of Neuropathology & Experimental Neurology:
August 2011 - Volume 70 - Issue 8 - pp 698-702
http://transmissiblespongiformencephalopathy.blogspot.com/2011/07/second-case-of-gerstmann-straussler.html
Saturday, August 14, 2010
BSE Case Associated with Prion Protein Gene Mutation (g-h-BSEalabama) and VPSPr PRIONPATHY
(see mad cow feed in COMMERCE IN ALABAMA...TSS)
http://prionpathy.blogspot.com/2010/08/bse-case-associated-with-prion-protein.html
Wednesday, June 15, 2011
Galveston, Texas - Isle port moves through thousands of heifers headed to Russia, none from Texas, Alabama, or Washington, due to BSE risk factor
http://transmissiblespongiformencephalopathy.blogspot.com/2011/06/galveston-texas-isle-port-moves-through.html
TSS
Thursday, August 4, 2011
Terry Singeltary Sr. on the Creutzfeldt-Jakob Disease Public Health Crisis, Date aired: 27 Jun 2011
Terry Singeltary, Sr. on the Creutzfeldt-Jakob Disease Public Health Crisis
Date aired: 27 Jun 2011
(see video here)
http://www.youtube.com/watch?v=c0tWkNvhO4g
http://www.youtube.com/watch?v=zf3lfz9NrT4&feature=results_main&playnext=1&list=PL780BE2AF0B62A944
source code ;
http://suprememastertv.com/services.php?bo_table=healthy&wr_id=159&target=copy
please note, i was never founder of CJD Watch, I just helped out there. CJD Watch has actually been dysfunctional for some time.
CJD Watch
http://www.fortunecity.com/healthclub/cpr/349/part1cjd.htm
CJD Watch message board updated ;
http://disc.yourwebapps.com/Indices/236650.html
HOWEVER, PLEASE SEE CJD VOICE, still alive and well ;
http://creativegumbo.net/cjdvoice/
so is CJD Voice message board ;
http://disc.yourwebapps.com/Indices/7498.html
for those interested, see also ;
http://www.blogger.com/profile/06986622967539963260
http://www.linkedin.com/profile/view?id=17373347&locale=en_US&trk=tab_pro
CJD BSE CWD SCRAPIE TSE PRION UPDATE AUGUST 2011
UPDATE JULY 2011 MORE OF THE "PENDING CLASSIFICATION CREUTZFELDT JAKOB DISEASE'' STEADY INCREASING...TSS
case; 5 Includes 13 cases in which the diagnosis is pending, and 18 inconclusive cases; 6 Includes 18 (15 from 2011) cases with type determination pending in which the diagnosis of vCJD has been excluded.
http://www.cjdsurveillance.com/pdf/case-table.pdf
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
Monday, August 9, 2010
National Prion Disease Pathology Surveillance Center Cases Examined (July 31, 2010)
(please watch and listen to the video and the scientist speaking about atypical BSE and sporadic CJD and listen to Professor Aguzzi)
http://prionunitusaupdate2008.blogspot.com/2010/08/national-prion-disease-pathology.html
Wednesday, March 31, 2010
Atypical BSE in Cattle
To date the OIE/WAHO assumes that the human and animal health standards set out in the BSE chapter for classical BSE (C-Type) applies to all forms of BSE which include the H-type and L-type atypical forms. This assumption is scientifically not completely justified and accumulating evidence suggests that this may in fact not be the case. Molecular characterization and the spatial distribution pattern of histopathologic lesions and immunohistochemistry (IHC) signals are used to identify and characterize atypical BSE. Both the L-type and H-type atypical cases display significant differences in the conformation and spatial accumulation of the disease associated prion protein (PrPSc) in brains of afflicted cattle. Transmission studies in bovine transgenic and wild type mouse models support that the atypical BSE types might be unique strains because they have different incubation times and lesion profiles when compared to C-type BSE.
When L-type BSE was inoculated into ovine transgenic mice and Syrian hamster the resulting molecular fingerprint had changed, either in the first or a subsequent passage, from L-type into C-type BSE. In addition, non-human primates are specifically susceptible for atypical BSE as demonstrated by an approximately 50% shortened incubation time for L-type BSE as compared to C-type. Considering the current scientific information available, it cannot be assumed that these different BSE types pose the same human health risks as C-type BSE or that these risks are mitigated by the same protective measures.
This study will contribute to a correct definition of specified risk material (SRM) in atypical BSE. The incumbent of this position will develop new and transfer existing, ultra-sensitive methods for the detection of atypical BSE in tissue of experimentally infected cattle.
http://www.prionetcanada.ca/detail.aspx?menu=5&dt=293380&app=93&cat1=387&tp=20&lk=no&cat2
Thursday, August 12, 2010
Seven main threats for the future linked to prions
First threat
The TSE road map defining the evolution of European policy for protection against prion diseases is based on a certain numbers of hypotheses some of which may turn out to be erroneous. In particular, a form of BSE (called atypical Bovine Spongiform Encephalopathy), recently identified by systematic testing in aged cattle without clinical signs, may be the origin of classical BSE and thus potentially constitute a reservoir, which may be impossible to eradicate if a sporadic origin is confirmed.
***Also, a link is suspected between atypical BSE and some apparently sporadic cases of Creutzfeldt-Jakob disease in humans. These atypical BSE cases constitute an unforeseen first threat that could sharply modify the European approach to prion diseases.
Second threat
snip...
http://www.neuroprion.org/en/np-neuroprion.html
http://prionpathy.blogspot.com/2010/08/seven-main-threats-for-future-linked-to.html
http://prionpathy.blogspot.com/
Rural and Regional Affairs and Transport References Committee
The possible impacts and consequences for public health, trade and agriculture of the Government's decision to relax import restrictions on beef Final report June 2010
2.65 At its hearing on 14 May 2010, the committee heard evidence from Dr Alan Fahey who has recently submitted a thesis on the clinical neuropsychiatric, epidemiological and diagnostic features of Creutzfeldt-Jakob disease.48 Dr Fahey told the committee of his concerns regarding the lengthy incubation period for transmissible spongiform encephalopathies, the inadequacy of current tests and the limited nature of our current understanding of this group of diseases.49
2.66 Dr Fahey also told the committee that in the last two years a link has been established between forms of atypical CJD and atypical BSE. Dr Fahey said that: They now believe that those atypical BSEs overseas are in fact causing sporadic Creutzfeldt-Jakob disease. They were not sure if it was due to mad sheep disease or a different form. If you look in the textbooks it looks like this is just arising by itself. But in my research I have a summary of a document which states that there has never been any proof that sporadic Creutzfeldt-Jakob disease has arisen de novo-has arisen of itself. There is no proof of that. The recent research is that in fact it is due to atypical forms of mad cow disease which have been found across Europe, have been found in America and have been found in Asia. These atypical forms of mad cow disease typically have even longer incubation periods than the classical mad cow disease.50
http://www.aph.gov.au/senate/committee/rrat_ctte/mad_cows/report/report.pdf
14th ICID International Scientific Exchange Brochure -
Final Abstract Number: ISE.114
Session: International Scientific Exchange
Transmissible Spongiform encephalopathy (TSE) animal and human TSE in North America update October 2009
T. Singeltary
Bacliff, TX, USA
Background:
An update on atypical BSE and other TSE in North America. Please remember, the typical U.K. c-BSE, the atypical l-BSE (BASE), and h-BSE have all been documented in North America, along with the typical scrapie's, and atypical Nor-98 Scrapie, and to date, 2 different strains of CWD, and also TME. All these TSE in different species have been rendered and fed to food producing animals for humans and animals in North America (TSE in cats and dogs ?), and that the trading of these TSEs via animals and products via the USA and Canada has been immense over the years, decades.
Methods:
12 years independent research of available data
Results:
I propose that the current diagnostic criteria for human TSEs only enhances and helps the spreading of human TSE from the continued belief of the UKBSEnvCJD only theory in 2009. With all the science to date refuting it, to continue to validate this old myth, will only spread this TSE agent through a multitude of potential routes and sources i.e. consumption, medical i.e., surgical, blood, dental, endoscopy, optical, nutritional supplements, cosmetics etc.
Conclusion:
I would like to submit a review of past CJD surveillance in the USA, and the urgent need to make all human TSE in the USA a reportable disease, in every state, of every age group, and to make this mandatory immediately without further delay. The ramifications of not doing so will only allow this agent to spread further in the medical, dental, surgical arena's. Restricting the reporting of CJD and or any human TSE is NOT scientific. Iatrogenic CJD knows NO age group, TSE knows no boundaries. I propose as with Aguzzi, Asante, Collinge, Caughey, Deslys, Dormont, Gibbs, Gajdusek, Ironside, Manuelidis, Marsh, et al and many more, that the world of TSE Transmissible Spongiform Encephalopathy is far from an exact science, but there is enough proven science to date that this myth should be put to rest once and for all, and that we move forward with a new classification for human and animal TSE that would properly identify the infected species, the source species, and then the route.
http://ww2.isid.org/Downloads/14th_ICID_ISE_Abstracts.pdf
READ THIS STUDY STUDY JUST OUT, AND SEE THE SOURCE DATA THERE FROM ;
Saturday, June 25, 2011
Transmissibility of BSE-L and Cattle-Adapted TME Prion Strain to Cynomolgus Macaque
"BSE-L in North America may have existed for decades"
http://transmissiblespongiformencephalopathy.blogspot.com/2011/06/transmissibility-of-bse-l-and-cattle.html
RE - "BSE-L in North America may have existed for decades" YA THINK ???
Over the next 8-10 weeks, approximately 40% of all the adult mink on the farm died from TME.
snip...
The rancher was a ''dead stock'' feeder using mostly (>95%) downer or dead dairy cattle...
http://web.archive.org/web/20030516051623/http://www.bseinquiry.gov.uk/files/mb/m09/tab05.pdf
Sunday, June 26, 2011
Risk Analysis of Low-Dose Prion Exposures in Cynomolgus Macaque
http://transmissiblespongiformencephalopathy.blogspot.com/2011/06/risk-analysis-of-low-dose-prion.html
Thursday, June 23, 2011
Experimental H-type bovine spongiform encephalopathy characterized by plaques and glial- and stellate-type prion protein deposits
http://transmissiblespongiformencephalopathy.blogspot.com/2011/06/experimental-h-type-bovine-spongiform.html
Thursday, July 21, 2011
A Second Case of Gerstmann-Sträussler-Scheinker Disease Linked to the G131V Mutation in the Prion Protein Gene in a Dutch Patient Journal of Neuropathology & Experimental Neurology:
August 2011 - Volume 70 - Issue 8 - pp 698-702
http://transmissiblespongiformencephalopathy.blogspot.com/2011/07/second-case-of-gerstmann-straussler.html
Saturday, August 14, 2010
BSE Case Associated with Prion Protein Gene Mutation (g-h-BSEalabama) and VPSPr PRIONPATHY
(see mad cow feed in COMMERCE IN ALABAMA...TSS)
http://prionpathy.blogspot.com/2010/08/bse-case-associated-with-prion-protein.html
Wednesday, June 15, 2011
Galveston, Texas - Isle port moves through thousands of heifers headed to Russia, none from Texas, Alabama, or Washington, due to BSE risk factor
http://transmissiblespongiformencephalopathy.blogspot.com/2011/06/galveston-texas-isle-port-moves-through.html
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 14, 2011
Valley Farm Meats (DBA Strasburg Provision, Inc) Issues Precautionary Recall for Beef Products Due to Possible Contamination with Prohibited Materials SRM
Ohio Department of Agriculture and Ohio Department of Health
http://transmissiblespongiformencephalopathy.blogspot.com/2011/07/valley-farm-meats-dba-strasburg.html
THE USA MAD COW FDA FEED BAN OF AUGUST 4, 1997 (PARTIAL AND VOLUNTARY) WAS NOTHING MORE THAN INK ON PAPER.
SEE THE MILLIONS AND TONS AND TONS OF BANNED HIGHLY SUSPECT MAD COW FEED IN COMMERCE IN USA, A DECADE LATER, 2007 ;
Saturday, November 6, 2010
TAFS1 Position Paper on Position Paper on Relaxation of the Feed Ban in the EU Berne, 2010 TAFS
INTERNATIONAL FORUM FOR TRANSMISSIBLE ANIMAL DISEASES AND FOOD SAFETY a non-profit Swiss Foundation
http://madcowfeed.blogspot.com/2010/11/tafs1-position-paper-on-position-paper.html
Archive Number 20101206.4364 Published Date 06-DEC-2010 Subject PRO/AH/EDR> Prion disease update 2010 (11)
PRION DISEASE UPDATE 2010 (11)
http://www.promedmail.org/direct.php?id=20101206.4364
NOW, what about that mad cow feed from atypical BSE in commerce and SRM regulations ???
Research Project: Study of Atypical Bse Location: Virus and Prion Research Unit
Project Number: 3625-32000-086-05 Project Type: Specific Cooperative Agreement
Start Date: Sep 15, 2004 End Date: Sep 14, 2009
Objective: The objective of this cooperative research project with Dr. Maria Caramelli from the Italian BSE Reference Laboratory in Turin, Italy, is to conduct comparative studies with the U.S. bovine spongiform encephalopathy (BSE) isolate and the atypical BSE isolates identified in Italy. The studies will cover the following areas: 1. Evaluation of present diagnostics tools used in the U.S. for the detection of atypical BSE cases. 2. Molecular comparison of the U.S. BSE isolate and other typical BSE isolates with atypical BSE cases. 3. Studies on transmissibility and tissue distribution of atypical BSE isolates in cattle and other species.
Approach: This project will be done as a Specific Cooperative Agreement with the Italian BSE Reference Laboratory, Istituto Zooprofilattico Sperimentale del Piemonte, in Turin, Italy. It is essential for the U.S. BSE surveillance program to analyze the effectiveness of the U.S diagnostic tools for detection of atypical cases of BSE. Molecular comparisons of the U.S. BSE isolate with atypical BSE isolates will provide further characterization of the U.S. BSE isolate. Transmission studies are already underway using brain homogenates from atypical BSE cases into mice, cattle and sheep. It will be critical to see whether the atypical BSE isolates behave similarly to typical BSE isolates in terms of transmissibility and disease pathogenesis. If transmission occurs, tissue distribution comparisons will be made between cattle infected with the atypical BSE isolate and the U.S. BSE isolate.
Differences in tissue distribution could require new regulations regarding specific risk material (SRM) removal.
http://www.ushrl.saa.ars.usda.gov/research/projects/projects.htm?accn_no=408490
Saturday, June 12, 2010
PUBLICATION REQUEST AND FOIA REQUEST Project Number: 3625-32000-086-05 Study of Atypical Bse
http://bse-atypical.blogspot.com/2010/06/publication-request-and-foia-request.html
Wednesday, July 28, 2010
re-Freedom of Information Act Project Number 3625-32000-086-05, Study of Atypical BSE UPDATE July 28, 2010
http://bse-atypical.blogspot.com/2010/07/re-freedom-of-information-act-project.html
Friday, October 8, 2010
Scientific reasons for a feed ban of meat-and-bone meal, applicable to all farmed animals including cattle, pigs, poultry, farmed fish and pet food
http://madcowfeed.blogspot.com/2010/10/scientific-reasons-for-feed-ban-of-meat.html
Wednesday, July 06, 2011
Swine Are Susceptible to Chronic Wasting Disease by Intracerebral Inoculation
(SEE MAD COW FEED BAN VIOLATIONS. WHAT FEED BAN ???)
http://chronic-wasting-disease.blogspot.com/2011/07/swine-are-susceptible-to-chronic.html
P.9.21
Molecular characterization of BSE in Canada
Jianmin Yang1, Sandor Dudas2, Catherine Graham2, Markus Czub3, Tim McAllister1, Stefanie Czub1 1Agriculture and Agri-Food Canada Research Centre, Canada; 2National and OIE BSE Reference Laboratory, Canada; 3University of Calgary, Canada
Background: Three BSE types (classical and two atypical) have been identified on the basis of molecular characteristics of the misfolded protein associated with the disease. To date, each of these three types have been detected in Canadian cattle.
Objectives: This study was conducted to further characterize the 16 Canadian BSE cases based on the biochemical properties of there associated PrPres. Methods: Immuno-reactivity, molecular weight, glycoform profiles and relative proteinase K sensitivity of the PrPres from each of the 16 confirmed Canadian BSE cases was determined using modified Western blot analysis.
Results: Fourteen of the 16 Canadian BSE cases were C type, 1 was H type and 1 was L type. The Canadian H and L-type BSE cases exhibited size shifts and changes in glycosylation similar to other atypical BSE cases. PK digestion under mild and stringent conditions revealed a reduced protease resistance of the atypical cases compared to the C-type cases. N terminal- specific antibodies bound to PrPres from H type but not from C or L type. The C-terminal-specific antibodies resulted in a shift in the glycoform profile and detected a fourth band in the Canadian H-type BSE.
Discussion: The C, L and H type BSE cases in Canada exhibit molecular characteristics similar to those described for classical and atypical BSE cases from Europe and Japan. This supports the theory that the importation of BSE contaminated feedstuff is the source of C-type BSE in Canada.
*** It also suggests a similar cause or source for atypical BSE in these countries.
http://www.prion2009.com/sites/default/files/Prion2009_Book_of_Abstracts.pdf
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
Monday, June 20, 2011 2011
Annual Conference of the National Institute for Animal Agriculture ATYPICAL NOR-98 LIKE SCRAPIE UPDATE USA
http://nor-98.blogspot.com/2011/06/2011-annual-conference-of-national.html
Monday, June 27, 2011
Comparison of Sheep Nor98 with Human Variably Protease-Sensitive Prionopathy and Gerstmann-Sträussler-Scheinker Disease
http://prionopathy.blogspot.com/2011/06/comparison-of-sheep-nor98-with-human.html
Monday, June 20, 2011 2011
Annual Conference of the National Institute for Animal Agriculture ATYPICAL NOR-98 LIKE SCRAPIE UPDATE USA
http://nor-98.blogspot.com/2011/06/2011-annual-conference-of-national.html
Monday, June 27, 2011
Comparison of Sheep Nor98 with Human Variably Protease-Sensitive Prionopathy and Gerstmann-Sträussler-Scheinker Disease
http://prionopathy.blogspot.com/2011/06/comparison-of-sheep-nor98-with-human.html
Thursday, July 14, 2011
Histopathological Studies of “CH1641-Like” Scrapie Sources Versus Classical Scrapie and BSE Transmitted to Ovine Transgenic Mice (TgOvPrP4)
http://transmissiblespongiformencephalopathy.blogspot.com/2011/07/histopathological-studies-of-ch1641.html
Monday, June 27, 2011
Zoonotic Potential of CWD: Experimental Transmissions to Non-Human Primates
http://chronic-wasting-disease.blogspot.com/2011/06/zoonotic-potential-of-cwd-experimental.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
Please see the following warning from CDC about prion TSE consumption in North America ;
Thursday, May 26, 2011
Travel History, Hunting, and Venison Consumption Related to Prion Disease Exposure, 2006-2007 FoodNet Population Survey
Journal of the American Dietetic Association Volume 111, Issue 6 , Pages 858-863, June 2011.
http://transmissiblespongiformencephalopathy.blogspot.com/2011/05/travel-history-hunting-and-venison.html
Monday, May 23, 2011
Atypical Prion Diseases in Humans and Animals 2011
Top Curr Chem (2011)
DOI: 10.1007/128_2011_161
# Springer-Verlag Berlin Heidelberg 2011
Michael A. Tranulis, Sylvie L. Benestad, Thierry Baron, and Hans Kretzschmar
Abstract
Although prion diseases, such as Creutzfeldt-Jakob disease (CJD) in humans and scrapie in sheep, have long been recognized, our understanding of their epidemiology and pathogenesis is still in its early stages. Progress is hampered by the lengthy incubation periods and the lack of effective ways of monitoring and characterizing these agents. Protease-resistant conformers of the prion protein (PrP), known as the "scrapie form" (PrPSc), are used as disease markers, and for taxonomic purposes, in correlation with clinical, pathological, and genetic data. In humans, prion diseases can arise sporadically (sCJD) or genetically (gCJD and others), caused by mutations in the PrP-gene (PRNP), or as a foodborne infection, with the agent of bovine spongiform encephalopathy (BSE) causing variant CJD (vCJD). Person-to-person spread of human prion disease has only been known to occur following cannibalism (kuru disease in Papua New Guinea) or through medical or surgical treatment (iatrogenic CJD, iCJD). In contrast, scrapie in small ruminants and chronic wasting disease (CWD) in cervids behave as infectious diseases within these species. Recently, however, so-called atypical forms of prion diseases have been discovered in sheep (atypical/Nor98 scrapie) and in cattle, BSE-H and BSE-L. These maladies resemble sporadic or genetic human prion diseases and might be their animal equivalents. This hypothesis also raises the significant public health question of possible epidemiological links between these diseases and their counterparts in humans.
M.A. Tranulis (*)
Norwegian School of Veterinary Science, Oslo, Norway
e-mail: Michael.Tranulis@nvh.no
S.L. Benestad
Norwegian Veterinary Institute, Oslo, Norway
T. Baron
Agence Nationale de Se´curite´ Sanitaire, ANSES, Lyon, France
H. Kretzschmar
Ludwig-Maximilians University of Munich, Munich, Germany
Keywords Animal Atypical Atypical/Nor98 scrapie BSE-H BSE-L Human Prion disease Prion strain Prion type
http://resources.metapress.com/pdf-preview.axd?code=f433r34h34ugg617&size=largest
snip...SEE MORE HERE ;
http://bse-atypical.blogspot.com/2011/05/atypical-prion-diseases-in-humans-and.html
Chronic Wasting Disease Prions in Elk Antler Velvet
Rachel C. Angers,1 Tanya S. Seward, Dana Napier, Michael Green, Edward Hoover, Terry Spraker, Katherine O'Rourke, Aru Balachandran, and Glenn C. Telling Author affiliations: University of Kentucky Medical Center, Lexington, Kentucky, USA (R.C. Angers, T.S. Seward, D. Napier, M. Green, G.C. Telling); Colorado State University, Fort Collins, Colorado, USA (E. Hoover, T. Spraker); US Department of Agriculture, Pullman, Washington, USA (K. O'Rourke); and Canadian Food Inspection Agency, Ottawa, Ontario, Canada (A. Balachandran) 1Current affiliation: MRC Laboratory of Molecular Biology, Cambridge, UK.
Chronic wasting disease (CWD) is a contagious, fatal prion disease of deer and elk that continues to emerge in new locations. To explore the means by which prions are transmitted with high efficiency among cervids, we examined prion infectivity in the apical skin layer covering the growing antler (antler velvet) by using CWD-susceptible transgenic mice and protein misfolding cyclic amplification. Our finding of prions in antler velvet of CWD-affected elk suggests that this tissue may play a role in disease transmission among cervids. Humans who consume antler velvet as a nutritional supplement are at risk for exposure to prions. The fact that CWD prion incubation times in transgenic mice expressing elk prion protein are consistently more rapid raises the possibility that residue 226, the sole primary structural difference between deer and elk prion protein, may be a major determinant of CWD pathogenesis.
please see full text ;
http://www.cdc.gov/eid/content/15/5/pdfs/08-1458.pdf
see history of mad cow in a pill, and a lot of folks out there were taking these things not know that some contained the most highly infectious materials that carry mad cow disease i.e. the PRION TSE agent. officials knew over a decade ago about this. put out a warning at the FDA about it...
May 9, 1996
TO MANUFACTURERS AND IMPORTERS OF DIETARY SUPPLEMENTS: TO MANUFACTURERS AND IMPORTERS OF COSMETICS:
As the media have widely reported, the British government announced on March 20, 1996, that new information had been gathered about bovine spongiform encephalopathy (BSE) in cattle that suggests a possible relationship between BSE and ten cases of a newly identified form of Creutzfeldt-Jakob disease (CJD), a similar fatal transmissible spongiform encephalopathy (TSE) in humans. To serve our mutual interest in protecting public health, the Food and Drug Administration (FDA) believes it is prudent to reiterate concerns we have previously expressed on this issue. BSE is a transmissible neurologic disorder of cattle and is prevalent in certain parts of the world. This neurological disease is one of a number of transmissible spongiform encephalopathies (TSE) known and is similar to other TSEs such as scrapie in sheep and CJD in humans. It is believed that the spread of BSE in cattle in some countries, particularly Great Britain, was caused by the feeding of infected cattle and sheep tissues to cattle. While transmission of the causative agent of BSE to humans has not been definitively documented to date, inter-species transfer has been demonstrated (e.g., mice can be infected by exposure to infected bovine tissues). Recent developments in Great Britain raise serious questions regarding potential hazards of the consumption of animal tissues containing the causative agent of BSE. Although there is still no definitive evidence that the consumption of bovine tissues that contain the transmissible agent for BSE cause CJD in humans, FDA is concerned that appropriate measures to eliminate the use of bovine tissues from BSE-countries be instituted industry-wide.
We strongly recommend that firms manufacturing or importing dietary supplements which contain specific bovine tissues (see appendix A), including extracts or substances derived from such tissues, take whatever steps are necessary to assure themselves and the public that such ingredients do not come from cattle born, raised, or slaughtered in countries where BSE exists. FDA believes that immediate and concrete steps should be taken by manufacturers to reduce the potential risk of human exposure to the infectious agent which causes BSE in cattle. The list of countries where BSE is known to exist is maintained by the U.S. Department of Agriculture (USDA) and codified in Title 9, Code of Federal Regulations, Part 94.18. The following is the current list: USDA LIST OF COUNTRIES WHERE BSE EXISTS (Current as of May 1996) Great Britain (including Northern Ireland and the Falklands) Switzerland France Republic of Ireland Oman Portugal A range of research projects into the exact nature of both the BSE agent and other TSE agents is ongoing. Available scientific information indicates that these agents are extremely resistant to inactivation by normal disinfection or sterilization procedures. A number of dietary supplement products use bovine-derived tissues or extracts of such tissues as ingredients. These ingredients include, for example, specific tissues and organs or their extracts (e.g., liver powder, "orchic" extracts, ovaries, eye tissue, mammary tissue), glandular powders or extracts (e.g., adrenal gland, thyroid gland), or specific substances extracted from glands or tissues (e.g., melatonin extracted from the pineal gland). At a future date, we will contact you with guidance on how best to provide assurance that your products do not contain potentially BSE-infected materials. We appreciate your attention to and cooperation in this matter. If you need more information, please contact Dr. Elisa Elliot by telephone at (202) 205-5140. Sincerely yours, /s/ Michael A. Friedman, M.D. Deputy Commissioner for Operations Enclosure Appendix A List of Tissues With Suspected Infectivity Category I (High infectivity) brain spinal cord Category II (Medium infectivity) ileum lymph nodes proximal colon spleen tonsil dura mater pineal gland placenta cerebrospinal fluid pituitary gland adrenal gland Category III (Low infectivity) distal colon nasal mucosa sciatic nerve bone marrow liver lung pancreas thymus gland
Thursday, March 19, 2009
Chronic Wasting Disease Prions in Elk Antler Velvet (Nutritional Supplements and CJD)
http://chronic-wasting-disease.blogspot.com/2009/03/chronic-wasting-disease-prions-in-elk.html
Wednesday, June 29, 2011
TSEAC Meeting August 1, 2011 donor deferral...
http://tseac.blogspot.com/2011/06/tseac-meeting-august-1-2011-donor.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
UPDATE JULY 2011 MORE OF THE "PENDING CLASSIFICATION CREUTZFELDT JAKOB DISEASE'' STEADY INCREASING...TSS
case; 5 Includes 13 cases in which the diagnosis is pending, and 18 inconclusive cases; 6 Includes 18 (15 from 2011) cases with type determination pending in which the diagnosis of vCJD has been excluded.
http://www.cjdsurveillance.com/pdf/case-table.pdf
Monday, August 9, 2010
National Prion Disease Pathology Surveillance Center Cases Examined (July 31, 2010)
(please watch and listen to the video and the scientist speaking about atypical BSE and sporadic CJD and listen to Professor Aguzzi)
http://prionunitusaupdate2008.blogspot.com/2010/08/national-prion-disease-pathology.html
Saturday, March 5, 2011
MAD COW ATYPICAL CJD PRION TSE CASES WITH CLASSIFICATIONS PENDING ON THE RISE IN NORTH AMERICA
http://transmissiblespongiformencephalopathy.blogspot.com/2011/03/mad-cow-atypical-cjd-prion-tse-cases.html
Tuesday, April 26, 2011
sporadic CJD RISING Text and figures of the latest annual report of the NCJDRSU covering the period 1990-2009 (published 11th March 2011)
http://creutzfeldt-jakob-disease.blogspot.com/2011/04/sporadic-cjd-rising-text-and-figures-of.html
Wednesday, June 29, 2011
TSEAC Meeting August 1, 2011 donor deferral...
http://tseac.blogspot.com/2011/06/tseac-meeting-august-1-2011-donor.html
Tuesday, March 29, 2011
TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY EXPOSURE SPREADING VIA HOSPITALS AND SURGICAL PROCEDURES AROUND THE GLOBE
http://transmissiblespongiformencephalopathy.blogspot.com/2011/03/transmissible-spongiform-encephalopathy.html
Sunday, May 1, 2011
W.H.O. T.S.E. PRION Blood products and related biologicals May 2011
http://transmissiblespongiformencephalopathy.blogspot.com/2011/05/who-tse-prion-blood-products-and.html
Saturday, April 30, 2011
Blood product, collected from a donor who was at risk for variant Creutzfeldt-Jakob disease (vCJD), was distributed APRIL 27, 2011
http://vcjdtransfusion.blogspot.com/2011/04/blood-product-collected-from-donor-who.html
Friday, June 17, 2011
Treatable neurological disorders misdiagnosed as Creutzfeldt-Jakob disease
http://creutzfeldt-jakob-disease.blogspot.com/2011/06/treatable-neurological-disorders.html
Saturday, January 22, 2011
Alzheimer's, Prion, and Neurological disease, and the misdiagnosis there of, a review 2011
http://transmissiblespongiformencephalopathy.blogspot.com/2011/01/alzheimers-prion-and-neurological.html
Friday, September 3, 2010
Alzheimer's, Autism, Amyotrophic Lateral Sclerosis, Parkinson's, Prionoids, Prionpathy, Prionopathy, TSE
http://betaamyloidcjd.blogspot.com/2010/09/alzheimers-autism-amyotrophic-lateral.html
Thursday, December 23, 2010
Alimentary prion infections: Touch-down in the intestine, Alzheimer, Parkinson disease and TSE mad cow diseases $ The Center for Consumer Freedom
http://betaamyloidcjd.blogspot.com/2010/12/alimentary-prion-infections-touch-down.html
Friday, November 30, 2007
CJD QUESTIONNAIRE USA CWRU AND CJD FOUNDATION
http://cjdquestionnaire.blogspot.com/2007/11/cjd-questionnaire.html
http://cjdquestionnaire.blogspot.com/
Einstein once said, 'The definition of insanity is doing the same thing over and over again and expecting different results.' re-transmission studies on TSE's...TSS
layperson
Terry S. Singeltary Sr. P.O. Box 42 Bacliff, Texas USA 77518 flounder9@verizon.net
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