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


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


1. The National Creutzfeldt-Jakob Disease Research and Surveillance Unit, The University of Edinburgh. CJD statistics. Available at:

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:

3. Transmissible spongiform encephalopathy agents: safe working and the prevention of infection. The ACDP TSE Risk Management Subgroup.

4. HPA CJD Incidents Panel [online]. Available at: 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.




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 Accepted 15 December 2008



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.


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


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.



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.


Wednesday, June 29, 2011

TSEAC Meeting August 1, 2011 donor deferral Saudi Arabia vCJD risk blood and blood products

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

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

grinding bone ???

Monday, January 17, 2011

Aerosols Transmit Prions to Immunocompetent and Immunodeficient Mice

Tuesday, August 12, 2008

Biosafety in Microbiological and Biomedical Laboratories Fifth Edition 2007 (occupational exposure to prion diseases)

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


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.;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

Tuesday, March 29, 2011


Saturday, March 5, 2011


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)

Thursday, August 4, 2011

Terry Singeltary Sr. on the Creutzfeldt-Jakob Disease Public Health Crisis, Date aired: 27 Jun 2011

Saturday, July 23, 2011


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

Archive Number 20101206.4364 Published Date 06-DEC-2010 Subject PRO/AH/EDR; Prion disease update 2010 (11)

PRION DISEASE UPDATE 2010 (11),F2400_P1001_PUB_MAIL_ID:1000,86129

Thursday, July 28, 2011

An Update on the Animal Disease Traceability Framework July 27, 2011

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"

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.


The rancher was a ''dead stock'' feeder using mostly (>95%) downer or dead dairy cattle...

Sunday, June 26, 2011

Risk Analysis of Low-Dose Prion Exposures in Cynomolgus Macaque

Thursday, June 23, 2011

Experimental H-type bovine spongiform encephalopathy characterized by plaques and glial- and stellate-type prion protein deposits

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

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)

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


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