Wednesday, August 24, 2011

All Clinically-Relevant Blood Components Transmit Prion Disease following a Single Blood Transfusion: A Sheep Model of vCJD

All Clinically-Relevant Blood Components Transmit Prion Disease following a Single Blood Transfusion: A Sheep Model of vCJD

Sandra McCutcheon1., Anthony Richard Alejo Blanco1., E. Fiona Houston2., Christopher de Wolf1, Boon Chin Tan1, Antony Smith3, Martin H. Groschup4, Nora Hunter1, Valerie S. Hornsey5, Ian R. MacGregor5, Christopher V. Prowse5, Marc Turner6, Jean C. Manson1* 1 The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Roslin, Edinburgh, United Kingdom, 2 School of Veterinary Medicine, College of Medical, Veterinary and Life Sciences, The University of Glasgow, Glasgow, United Kingdom, 3 The Institute for Animal Health, Compton, Berkshire, United Kingdom, 4 Institute for Novel and Emerging Infectious Diseases, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Germany, 5 National Science Laboratory, Scottish National Blood Transfusion Service (SNBTS), Edinburgh, United Kingdom, 6 University of Edinburgh and SNBTS, Edinburgh, United Kingdom


Variant CJD (vCJD) is an incurable, infectious human disease, likely arising from the consumption of BSE-contaminated meat products. Whilst the epidemic appears to be waning, there is much concern that vCJD infection may be perpetuated in humans by the transfusion of contaminated blood products. Since 2004, several cases of transfusion-associated vCJD transmission have been reported and linked to blood collected from pre-clinically affected donors. Using an animal model in which the disease manifested resembles that of humans affected with vCJD, we examined which blood components used in human medicine are likely to pose the greatest risk of transmitting vCJD via transfusion. We collected two full units of blood from BSE-infected donor animals during the pre-clinical phase of infection. Using methods employed by transfusion services we prepared red cell concentrates, plasma and platelets units (including leucoreduced equivalents). Following transfusion, we showed that all components contain sufficient levels of infectivity to cause disease following only a single transfusion and also that leucoreduction did not prevent disease transmission. These data suggest that all blood components are vectors for prion disease transmission, and highlight the importance of multiple control measures to minimise the risk of human to human transmission of vCJD by blood transfusion.

Citation: McCutcheon S, Alejo Blanco AR, Houston EF, de Wolf C, Tan BC, et al. (2011) All Clinically-Relevant Blood Components Transmit Prion Disease following a Single Blood Transfusion: A Sheep Model of vCJD. PLoS ONE 6(8): e23169. doi:10.1371/journal.pone.0023169 Editor: Matthew Baylis, University of Liverpool, United Kingdom Received March 17, 2011; Accepted July 8, 2011; Published August 17, 2011 Copyright:  2011 McCutcheon et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This is an independent report commissioned and funded by the Policy Research Programme in the Department of Health, UK (007/0162). The views expressed in the publication are those of the authors and not necessarily those of the Department of Health. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. * E-mail: . These authors contributed equally to this work



We have shown that all of the blood components investigated, whole blood, plasma, red cells, platelets and buffy coat, are capable of transmitting BSE infection following transfusion into susceptible sheep. Although infectivity has consistently been detected in plasma in rodent scrapie models, this is the first time that transmission of prion disease has been demonstrated following transfusion of plasma units collected from pre-clinical donors, and prepared to the same specifications as non-fractionated human plasma. While the results with platelets and leucocytes are similar to that of Mathiason et al. [30], the plasma results are strikingly different. In the previous study, prion infected cell-free plasma appeared not to cause disease following transfusion in deer. The reason for this is not clear and may relate to either a difference in the distribution of PrPSc and/or infectivity in different host species or indeed the strain of infectious agent used.

We also observed a number of cases in which leucoreduced components have caused BSE in recipients following transfusion. Other recipients of leucoreduced components are also now showing early signs of TSE infection and we would therefore expect more positive transmissions of BSE from these components. These data demonstrate that leucoreduction of blood components alone is insufficient to prevent transmission of prion infection via blood transfusion [23]. All four of the documented transfusionrelated transmissions of vCJD infectivity to date have occurred in individuals who received red cells (the most commonly transfused blood component) which were non-leucoreduced, between 1996 and 1999. Eighteen surviving recipients [36] transfused with red blood cells (n= 6), cryodepleted plasma (n =1) and leucoreduced red blood cells (n =11) from donors who were subsequently confirmed to have vCJD are still being followed up (personal communication from Miss J. McKenzie and Prof. R.G. Will, TMER study). There are a small number of cases of clinical vCJD with a history of blood transfusion, where no donor has developed clinical vCJD but where transfusion remains the possible source of infection. The most recent of these cases (2002) received leucoreduced red cells. Our findings would suggest that residual infectivity following leucoreduction may still pose a risk of transmission in a transfusion setting [23,37,38].

These transfusion studies were conducted in sheep, in which many effects of polymorphisms associated with the prnp gene (which modulates susceptibility to prion infection) are well understood. Similarly, the age at which donors and recipients were exposed to BSE prions, the infectious dose (in donor sheep) and the route of infection were relatively well controlled. Despite the control of known variables within this experiment, we observed significant variability in the incubation period of both orally infected donors and transfused recipients. During the course of this study we identified a novel effect of an existing polymorphism in the sheep PRNP gene, which modulates the incubation period of orally infected BSE donors (unpublished observations). While some of the variability in incubation periods of transfused recipients is likely associated with other genetic factors [39,40,41], it is also likely to be influenced by variability in prion titre in blood from donor sheep. It must also be recognised that in this model, incubation period is not considered an indicator of titre of infectivity in blood, since a full titration of infected blood has not yet been undertaken in sheep. However, given that BSE occurred in recipients following a single blood transfusion from donors who were healthy at the time of blood donation, we would suggest that even when or if the infectious load is low, disease can result if the route of transmission, i.e. blood transfusion, is highly efficient. Whilst we have clearly shown that blood collected from donor animals at a single time point is infectious, what remains unclear is when prion-associated infectivity first appears in blood, how it relates to incubation period and how the titre of infection changes as disease progresses. We are investigating these questions by inoculating transgenic mice with blood collected at various time points throughout the incubation period, from the same donor sheep as used in this study. This will allow us to address the duration, pattern and titre of prion infectivity in blood.

Our data raises considerable questions concerning the distribution of infectivity in blood, including its potential association with cell types other than leucocytes i.e. red cells and platelets, and/or other proteins or soluble components of plasma. Our data relating to the current transmission efficiencies of each component suggest whole blood and buffy coat represent the greatest risk in terms of transfusion and blood safety. However, these data may change over the full time course of this study and therefore it is too early to draw definitive conclusions. Furthermore, the blood components used in this study (including leucoreduced equivalents) were not purified cell populations, but also contained plasma and leucocytes to reflect the nature of the components routinely transfused in human patients. This may complicate understanding the process of identifying the relationship between the infectious agent and cell targets. It is also possible that mechanisms such as release of membrane fractions during processing [42] or shedding/transit by plasma membrane-derived microvesicles [43,44] may also contribute to the dissemination of infectivity in blood. It will be critical to understand how prion infectivity associates with particular blood components, and may identify new targets for diagnostics, therapeutics and allow for more refined risk reduction strategies.

Whilst these findings highlight the difficulties in predicting incubation times and the clinical outcomes associated with transfusion-related transmission of vCJD in humans (because of the extensive variability of individuals in terms of age, genetic background, titre and route by which one could be exposed) these data have clear implications for transfusion practices. We demonstrate the potential risk of acquiring vCJD from any blood component used in routine transfusion medicine, following a single transfusion from asymptomatic individuals.

While there has been recent, significant, developments in the quest for a blood-based assay to detect prion infection in symptomatic individuals [45], implementing such assays in the blood transfusion service to detect asymptomatic donors requires extensive validation. Thus there currently remains the potential for human to human transmission of vCJD via blood transfusion from individuals carrying the infectious agent but not showing clinical signs of disease. Our data suggests that leucoreduction alone is inadequate to minimise the risk of transmission of vCJD and to ensure the safety of blood used in transfusions and ultimately to safeguard public health.;jsessionid=198F52B91A67C1A9520EB62354DB5D93.ambra01?utm_medium=feed&utm_campaign=Feed%3A+plosone%2FPLoSONE+(PLoS+ONE+Alerts%3A+New+Articles)&utm_source=feedburner&articleURI=info%3Adoi%2F10.1371%2Fjournal.pone.0023169

Wednesday, June 29, 2011

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


Transmission Results in Squirrel Monkeys Inoculated with Human sCJD, vCJD, and GSS Blood Specimens: the Baxter Study

Brown, P1; Gibson, S2; Williams, L3; Ironside, J4; Will, R4; Kreil, T5; Abee, C3 1Fondation Alliance BioSecure, France; 2University of South Alabama, USA; 3University of Texas MD Anderson Cancer Center, USA; 4Western General Hospital, UK; 5Baxter BioSience, Austria

Background: Rodent and sheep models of Transmissible Spongiform Encephalopathy (TSE) have documented blood infectivity in both the pre-clinical and clinical phases of disease. Results in a (presumably more appropriate) non-human primate model have not been reported.

Objective: To determine if blood components (red cells, white cells, platelets, and plasma) from various forms of human TSE are infectious.

Methods: Blood components were inoculated intra-cerebrally (0.1 ml) and intravenously (0.5 ml) into squirrel monkeys from 2 patients with sporadic Creutzfeldt- Jakob disease (sCJD) and 3 patients with variant Creutzfeldt-Jakob disease (vCJD). Additional monkeys were inoculated with buffy coat or plasma samples from chimpanzees infected with either sCJD or Gerstmann-Sträussler-Scheinker disease (GSS). Animals were monitored for a period of 5 years, and all dying or sacrificed animals had post-mortem neuropathological examinations and Western blots to determine the presence or absence of the misfolded prion protein (PrPTSE).

Results: No transmissions occurred in any of the animals inoculated with blood components from patients with sporadic or variant CJD. All donor chimpanzees (sCJD and GSS) became symptomatic within 6 weeks of their pre-clinical phase plasmapheresis, several months earlier than the expected onset of illness. One monkey inoculated with purified leukocytes from a pre-clinical GSS chimpanzee developed disease after 36 months.

Conclusion: No infectivity was found in small volumes of blood components from 4 patients with sporadic CJD and 3 patients with variant CJD. ***However, a single transmission from a chimpanzee-passaged strain of GSS shows that infectivity may be present in leukocytes, and the shock of general anaesthesia and plasmspheresis appears to have triggered the onset of illness in pre-clinical donor chimpanzees.

Saturday, September 5, 2009



Friday, August 12, 2011

Creutzfeldt-Jakob disease (CJD) biannual update (2011/2), Incidents Panel, National Anonymous Tonsil Archive

Sunday, August 21, 2011

The British disease, or a disease gone global, The TSE Prion Disease

Thursday, August 4, 2011

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

see video here ;

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"

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

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


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


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.



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.




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 ;

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)

Sunday, August 21, 2011

Classical Bovine Spongiform Encephalopathy by Transmission of H-Type Prion in Homologous Prion Protein Context

Volume 17, Number 9-September 2011


Thursday, July 28, 2011

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

Thursday, July 14, 2011

Histopathological Studies of "CH1641-Like" Scrapie Sources Versus Classical Scrapie and BSE Transmitted to Ovine Transgenic Mice (TgOvPrP4)

Monday, June 20, 2011 2011

Annual Conference of the National Institute for Animal Agriculture ATYPICAL NOR-98 LIKE SCRAPIE UPDATE USA

Thursday, June 2, 2011

USDA scrapie report for April 2011 NEW ATYPICAL NOR-98 SCRAPIE CASES Pennsylvania AND California

Monday, June 27, 2011

Comparison of Sheep Nor98 with Human Variably Protease-Sensitive Prionopathy and Gerstmann-Sträussler-Scheinker Disease


Monday, June 27, 2011

Zoonotic Potential of CWD: Experimental Transmissions to Non-Human Primates


Wednesday, September 08, 2010


Wednesday, January 5, 2011



David W. Colby1,* and Stanley B. Prusiner1,2

Wednesday, July 06, 2011

Swine Are Susceptible to Chronic Wasting Disease by Intracerebral Inoculation

Thursday, April 03, 2008

A prion disease of cervids: Chronic wasting disease

2008 1: Vet Res. 2008 Apr 3;39(4):41

A prion disease of cervids: Chronic wasting disease

Sigurdson CJ.


*** twenty-seven CJD patients who regularly consumed venison were reported to the Surveillance Center***,


full text ;



Perceptions of unconventional slow virus diseases of animals in the USA

Spraker suggested an interesting explanation for the occurrence of CWD. The deer pens at the Foot Hills Campus were built some 30-40 years ago by a Dr. Bob Davis. At or about that time, allegedly, some scrapie work was conducted at this site. When deer were introduced to the pens they occupied ground that had previously been occupied by sheep. Whether they were scrapie infected sheep or not is unclear.


October 1994

Mr R.N. Elmhirst Chairman British Deer Farmers Association Holly Lodge Spencers Lane BerksWell Coventry CV7 7BZ

Dear Mr Elmhirst,


Thank you for your recent letter concerning the publication of the third annual report from the CJD Surveillance Unit. I am sorry that you are dissatisfied with the way in which this report was published.

The Surveillance Unit is a completely independant outside body and the Department of Health is committed to publishing their reports as soon as they become available. In the circumstances it is not the practice to circulate the report for comment since the findings of the report would not be amended. In future we can ensure that the British Deer Farmers Association receives a copy of the report in advance of publication.

The Chief Medical Officer has undertaken to keep the public fully informed of the results of any research in respect of CJD. This report was entirely the work of the unit and was produced completely independantly of the the Department.

The statistical results reqarding the consumption of venison was put into perspective in the body of the report and was not mentioned at all in the press release. Media attention regarding this report was low key but gave a realistic presentation of the statistical findings of the Unit. This approach to publication was successful in that consumption of venison was highlighted only once by the media ie. in the News at one television proqramme.

I believe that a further statement about the report, or indeed statistical links between CJD and consumption of venison, would increase, and quite possibly give damaging credence, to the whole issue. From the low key media reports of which I am aware it seems unlikely that venison consumption will suffer adversely, if at all.

Sunday, July 03, 2011

Prion Disease Detection, PMCA Kinetics, and IgG in Urine from Naturally/Experimentally Infected Scrapie Sheep and Preclinical/Clinical CWD Deer


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.

NOR IS THE FDA recalling this CWD positive elk meat for the well being of the dead elk ;

Wednesday, March 18, 2009

Noah's Ark Holding, LLC, Dawson, MN RECALL Elk products contain meat derived from an elk confirmed to have CWD NV, CA, TX, CO, NY, UT, FL, OK RECALLS AND FIELD CORRECTIONS: FOODS CLASS II

Monday, August 8, 2011

Susceptibility of Domestic Cats to CWD Infection


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