FDA’s Currently-Recommended Policies to Reduce the Possible Risk of Transmission of CJD and vCJD by Blood and Blood Products 2011 ???

FDA’s Currently-Recommended Policies to Reduce the Possible Risk of Transmission of CJD and vCJD by Blood and Blood Products 2011 ???

Informational Issue Summary

FDA’s Currently-Recommended Policies to Reduce the Possible Risk of Transmission of Creutzfeldt-Jakob Disease (CJD) and Variant Creutzfeldt-Jakob Disease (vCJD) by Blood and Blood Products

Transmissible Spongiform Encephalopathies Advisory Committee 22nd Meeting October 28-29, 2010

Gaithersburg, Maryland

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Background

Beginning in 1978, results of experimental studies repeatedly demonstrated that the infectious agents causing the transmissible spongiform encephalopathies (TSE agents or prions) are often found in the blood of infected animals, both during the incubation period and throughout overt illness. Since 1983, the FDA, issuing a series of guidances, has periodically recommended to the blood industry steps intended to reduce the theoretical risk of transmitting the infectious agents of the transmissible spongiform encephalopathies (TSEs) causing Creutzfeldt-Jakob disease (CJD) and variant CJD (vCJD) by blood and blood products. The risk of transmitting most forms of CJD by transfusions of blood components and injection of plasma derivatives, remains theoretical (see Appendices I and II), however, limited but convincing evidence strongly implicates transfusions with a blood component and injections of a human plasma-derived coagulation factor in iatrogenic transmissions of vCJD in the United Kingdom (UK). The history of FDA’s policies and of the science that informed the FDA in this area is summarized in Appendices I and II, with current FDA guidance in tabular form in Appendices V and VI. (Appendices III and IV summarize certain legislation implemented in the European Union and USDA regulations relevant to FDA blood safety policies.)

In principle, when possible, several approaches are taken to reduce the risk of transmitting infectious diseases from a blood or plasma donor to a recipient:

___________________________________________________________________________

Five “tiers” of safety for blood and components as related to CJD and vCJD (modified from Keeping Blood Transfusions Safe: FDA's Multi-layered Protections for Donated Blood. US FDA Publication No. FS 02-1, February 2002

http://www.fda.gov/BiologicsBloodVaccines/SafetyAvailability/BloodSafety/ucm095522.htm


accessed October 2010)

___________________________________________________________________________

1. Donor screening [questionnaires]: selection of blood and plasma donors based on deferrals for medical, geographical and behavioral risk factors; deferral registries to avoid collection and use of units from identified “unsuitable” donors

2. Laboratory testing of donor blood samples for markers of blood-transmissible diseases (infectious agents)

3. Donor Deferral Registries: an additional control to avoid collecting blood or releasing blood from donors deferred as unsuitable

4. Quarantine: Donor blood [and plasma] quarantined until testing results available

5. Problems and deficiencies: manufacturing problems investigated, deficiencies corrected, FDA notified of deviations

___________________________________________________________________________

1, 3 and 5 are currently applicable to TSEs; laboratory testing (2 and 4) is not yet available for TSEs. In addition to protections listed, pathogen reduction techniques are currently under study for both conventional pathogens and TSE agents but are not yet validated, approved or available.

___________________________________________________________________________

Because no validated screening tests identify TSE-agent-infected blood and there are no US-approved devices to remove TSE infectivity from blood and blood components, CJD and vCJD safety must continue to rely on precautionary deferrals of donors at increased risk for CJD and for vCJD and withdrawal of in-date components when post-donation

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information reveals that a donor should have been deferred; and, additionally for vCJD, withdrawal of plasma derivatives if and when a donor is found to have vCJD or possible vCJD. The FDA continues to encourage the development of donor screening tests and devices to remove the infectious agents of TSEs from blood (see below). The FDA, aware of the uncertainties surrounding the magnitude of the risk, the effectiveness of available risk-reducing measures, and the potential for contributing to shortages of life-sustaining blood products, has continued to review at frequent intervals its policies regarding CJD and vCJD. In particular, FDA blood safety policies regarding CJD and vCJD have periodically been reviewed publicly with the TSEAC, especially when new information suggested that risks should be reevaluated. In the appendices we provide additional current relevant information on risks of transfusion-transmitted and plasma-derivative-transmitted vCJD.

______________________________________________________________________________________

General approaches of FDA policies to reduce risk of transmitting CJD and vCJD by blood products

______________________________________________________________________________________ ?

Reduce risk that a donor was exposed to the agent of bovine spongiform encephalopathy (BSE)

Dietary exposure “geographic” risk-adjusted deferrals: defer some donors who resided in some BSE countries (or were potentially exposed on military bases that imported beef from UK)

Other exposure: defer donors who injected UK bovine insulin

Reduce risk that donor was exposed to vCJD agent of human origin

Defer donors with a history of transfusion in UK after 1980

Defer donors with a history of transfusion in France after 1980

Other steps were discussed at TSEAC meetings, but FDA was not advised to consider: history of transfusion in other BSE country besides UK and France after 1980; history of surgery in high-risk BSE countries after 1980 (suggested by one TSEAC member)

______________________________________________________________________________________

There have been six general bases for FDA’s recommended CJD/vCJD-related deferrals since 1983:

A. General CJD risk reduction. (1) CJD in a donor, (2) history of treatment with human cadaveric pituitary growth hormone or a dura mater allograft, and (3) history of CJD in a relative unless confirmed to be other than familial CJD or the donor PRNP genotype is found to be normal

B. vCJD risk reduction. (4) history of prolonged residence in most BSE countries (defined by USDA list of BSE-related import restrictions at 9 ) currently including UK, France or other European countries west of the Former Soviet Union (or residence/employment on a US military base in Europe during periods when beef was procured from UK), (5) history of transfusion in UK, or—more recently—history of transfusion in France, in or after 1980, and (6) injection with bovine insulin of UK origin in or after 1980

The most recent FDA CJD/vCJD-related donor deferral policies and the history of those are explained in full in FDA guidance issued on May 10, 2010

(http://www.fda.gov/downloads/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/UCM213415.pdf),


including minor modifications of the guidance of January 12, 2002. The following is a reduced summary of the essential features of the policy:

______________________________________________________________________________________

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Summary of Current FDA CJD/vCJD-related Recommendations for Deferral of Blood Donors and Plasma Donors (see FDA guidance document issued May 10, 2010 at

http://www.fda.gov/downloads/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/UCM213415.pdf)


______________________________________________________________________________________

Indefinitely defer all donors of Whole Blood and Source Plasma who

have any form of CJD or are at increased risk of CJD (received dura mater allograft, were injected with human cadaveric pituitary growth hormone, have a relative with CJD unless familial CJD has been ruled out

spent 3 mo in UK from Jan 1, 1980 to Dec 31, 1996, or

who ever had blood transfusion in UK or in France from 1980 to present, or

who ever injected UK bovine insulin prepared in or after 1980, or

spent 5 yr in France from Jan 1, 1980 to the present

spent 6 mo on US military bases from Jan 1, 1980 to end of 1990 north of Alps or end of 1996 south of Alps Indefinitely defer all donors of Whole Blood but not donors of Source Plasma who

spent 5 yr in Europe from Jan 1, 1980 to the present (including time in spent in UK 1980-1996 and France 1980-present) Exempt from deferrals are

Donors of Source Plasma who spent time of any duration in Europe except UK and France

Donors of plasma/serum to manufacture FDA-approved non-injectable products (appropriately labeled per guidance of May 10, 2010)

______________________________________________________________________________________

The FDA-recommended CJD/vCJD-related blood safety policies are intended to reduce the risk that a blood or plasma donor might be incubating CJD of any kind while not deferring so many donors as to compromise the supply of blood products. The FDA’s assessment in advance of the January 2002 guidance estimated that the recommended deferral policy would reduce donor risk of dietary exposure to BSE agent by approximately 90% while deferring some 7% of otherwise suitable blood donors. The 2010 guidance—adding a deferral of donors transfused in France from 1980 to the present, as previously recommended for donors transfused in the UK—while reducing the risk of transfusion-transmitted vCJD by only a small amount, is expected to defer very few donors who would not have been previously deferred because they resided in France for five years or more.

As always, blood and plasma establishments may implement additional more stringent requirements. If they choose to do so, FDA encourages them to assess the possibility that such actions will contribute to shortages and to undertake preemptive donor recruitment efforts to prevent shortages. Recognition by FDA of USDA BSE-related import restrictions under 9 CFR 94.18 as a basis for FDA donor deferral policies. Since the FDA’s 1999 guidance, the FDA has acknowledged the USDA’s list of countries under restriction for the importation of live cattle and beef products into the US at 9 CFR 94.18 (“USDA BSE List” summarized in Appendix V) as a basis for identifying countries with increased risk of human food-

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associated exposure to the BSE agent; most of the countries currently on the USDA BSE list are also listed on the current FDA donor deferral list (see Appendix IV), with three exceptions: the FDA has concluded that time spent in the UK after the end of 1996 should no longer pose an unacceptable risk of food-borne exposure to donors because of stringent food and animal feed controls implemented in the UK by that time; those measures were described at a TSEAC meeting


http://www.fda.gov/downloads/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/UCM213415.pdf



Time spent in Israel (one case of BSE reported in 2001) and Japan (36 cases of BSE detected from 2001 through 2009) have not been taken as a reason to defer blood donors; FDA had no information to predict the number of otherwise suitable donors who would be deferred because of time spent in Israel or Japan, and FDA had concern that those numbers might be substantial in certain areas of the US.

Prospects for future modifications of FDA blood and plasma deferral policies to reduce the Possible Risk of Transmitting Creutzfeldt-Jakob Disease (CJD) and Variant Creutzfeldt-Jakob Disease (vCJD) by Blood and Blood Products

Prospects for donor screening tests. As mentioned above, the FDA recognizes the potential value of practical blood tests to detect and defer infected donors of blood and plasma during the asymptomatic incubation periods of vCJD and CJD. FDA continues to encourage the development and validation of such tests and has several times arranged for developers of candidate tests present interim progress reports of their investigations at open meetings of TSEAC and received advice from TSEAC regarding possible pathways leading to FDA licensure of validated donor screening tests

http://www.fda.gov/ohrms/dockets/ac/06/transcripts/2006-4240t2.pdf


Effective testing would be a particularly attractive option for interdicting donors incubating forms of CJD other than vCJD, because no cases of transfusion-transmitted CJD or plasma-derivative-transmitted CJD have been detected in a lookback study (Dorsey, Zou et al. 2009), and many donors currently deferred because of risk factors for CJD might be re-entered if validated screening tests with high negative predictive values were not reactive. At the moment, no blood test has been validated as suitable for donor screening

http://biotuesday.ca/2010/05/31/amorfix-suspends-blood-testing-for-vcjd


Prospects for prion-protein and infectivity removal devices. Three TSE infectivity reduction devices, in development, have targeted the RBC component of Whole Blood. Two of the devices both deplete white blood cells (leukoreduction [LR]) and reduce the content of TSE agents in pilot studies. One of these devices is a modified LR filter containing several layers of prion-protein-removing material (Sowemimo-Coker, Demczyk et al. 2010. The second manufacturer is developing a combined LR and prion removal device (Miura M, Nirasawa H et al. in Abstracts of the AABB Meeting, 2006 SP221. Evaluation of a new combination filter for prion and leukoreduction (LR) of red cell concentrates (RCC), accessible at

http://onlinelibrary.wiley.com/doi/10.1111/j.1537-2995.2006.01023_1.x/pdf


The third filter is applied to leukoreduced RBC; the active component is a proprietary ligand claimed to adsorb both brain-derived and endogenous blood infectivity (Gregori, Gurgel et al. 2006). This filter was evaluated for safety and impact on component quality in the UK (Cahill, Murphy et al 2010; Wiltshire, Thomas et al. 2010). In April 2009 an independent UK Advisory Committee on Safety of Blood, Tissues and Organs (SaBTO recommended that “ …UK blood services … prepare to enable implementation of Prion filtration as soon as

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practicable, should a final recommendation to do so be made.”


http://www.dh.gov.uk/prod_consum_dh/groups/dh_digitalassets/@dh/@ab/documents/digitalasset/dh_099922.pdf



and later, in October 2009, recommended, with reservations, that “… filtered red cells be provided to those born since 1 January 1996, subject to satisfactory completion of …[an ongoing]… clinical trial”


http://www.dh.gov.uk/prod_consum_dh/groups/dh_digitalassets/@dh/@ab/documents/digitalasset/dh_108860.pdf


http://www.dh.gov.uk/prod_consum_dh/groups/dh_digitalassets/@dh/@ab/documents/digitalasset/dh_112477.pdf



—presumably because the risk of food-borne exposure to the BSE agent should be considerably less in younger than for older UK residents, for whom the reduced risk offered by filtration might be more difficult to justify. No “prion filter” device has been licensed for use in the US. Representatives of the sponsors developing the three devices are to describe some of their findings at the FDA TSE Advisory Committee meeting on October 29, 2010


(http://www.fda.gov/AdvisoryCommittees/CommitteesMeetingMaterials/BloodVaccinesandOtherBiologics/TransmissibleSpongiformEncephalopathiesAdvisoryCommittee/ucm225805.htm).


Implementation of measures to reduce dietary risk of exposure to the BSE agent in countries other that the UK. As presented to the 21st meeting of TSEAC on June 12, 2009


(http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/BloodVaccinesandOtherBiologics/TransmissibleSpongiformEncephalopathiesAdvisoryCommittee/UCM171810.pdf),




the European Commission (EC) has promulgated legislation (EC Regulation 999, 2001) obligatory throughout the European Union (EU) requiring implementation of a number of BSE-risk-reducing steps (see Appendix IV) similar to those implemented earlier in the UK (Appendix IV). The FDA has, with some exceptions, based recommendations to defer blood and plasma donors at increased risk of BSE exposure on the USDA import restriction list at 9 CFR 94.18 to determine when those steps have been adequately and uniformly implemented in various countries.


International recognition of BSE status of countries and of the declining BSE epidemics. The EC Scientific Steering Committee, in January 2000, recommended grouping countries based on their geographical BSE risk (GBR)



http://ec.europa.eu/food/fs/sc/ssc/out68_en.pdf



Four groups were recognized:

GBR I: highly unlikely to have BSE;

GBR II: unlikely but not excluded;

GBR III: likely but not confirmed or confirmed at a low level; GBR IV: confirmed at a high level. That system for evaluating BSE risk was once widely used but is no longer supported.

The World Organisation for Animal Health (OIE) subsequently developed a system to evaluate national BSE risk based on voluntary submissions of information to an ad hoc committee for BSE status based on five main criteria used to assess the BSE risk for the cattle population of a country: risk assessment for BSE occurrence; on-going program to encourage reporting of neurological diseases in adult cattle; compulsory notification and investigation of all cattle showing BSE-like symptoms; BSE active surveillance; testing of cattle brain or other tissues. The OIE currently assigns to each country one of three BSE risk categories: negligible, controlled or undetermined (for those countries that either did not apply or failed to be classified). As of May 2010, 47 countries had been assigned a BSE risk status by the OIE: 13 countries (including three on the USDA BSE

7

Import Restriction List) had been assigned negligible BSE risk status, and 34 countries, including the US and Canada, were recognized as having controlled BSE risk—the same risk status assigned to most European countries including the UK and France (http://www.oie.int/eng/Status/BSE/en_BSE_free.htm). The FDA welcomes efforts to improve estimates of relative risk for exposure to the BSE agent in beef products of various national origins and to develop an international BSE risk evaluation system acceptable to US authorities and those of other countries. ...

snip...see full text ;


http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/BloodVaccinesandOtherBiologics/TransmissibleSpongiformEncephalopathiesAdvisoryCommittee/UCM231179.pdf





When the OIE and the USDA et al collaborated to make legal the trading of Transmissible Spongiform Encephalopathy, when they did away with the BSE GBR risk assessments, where the USA, Canada, and Mexico were categorized as BSE GBR III.



please see ;



EFSA concludes that the current GBR level of USA is III, i.e. it is likely but not confirmed that domestic cattle are (clinically or pre-clinically) infected with the BSE-agent. As long as there are no significant changes in rendering or feeding, the stability remains extremely/very unstable. Thus, the probability of cattle to be (pre-clinically or clinically) infected with the BSE-agent persistently increases.



http://www.efsa.europa.eu/EFSA/efsa_locale-1178620753812_1211902594180.htm



Annex to the EFSA Scientific Report (2004) 3, 1-17 on the Assessment of the Geographical BSE Risk of USA

please see full text ;


http://www.efsa.europa.eu/en/scdocs/doc/3rax1.pdf



October 28-29, 2010:

Transmissible Spongiform Encephalopathies Advisory Committee Meeting References Document Posted: 10/26/2010


http://www.fda.gov/AdvisoryCommittees/CommitteesMeetingMaterials/BloodVaccinesandOtherBiologics/TransmissibleSpongiformEncephalopathiesAdvisoryCommittee/ucm231016.htm



October 28-29, 2010:

Transmissible Spongiform Encephalopathies Advisory Committee Meeting A 2010 Update of the Draft Quantitative Risk Assessment of vCJD Risk Potentially Associated with the Use of Human Plasma-Derived Factor VIII Manufactured Under United States (US) License From Plasma Collected in the US (PDF - 662KB) Posted: 10/26/2010


http://www.fda.gov/AdvisoryCommittees/CommitteesMeetingMaterials/BloodVaccinesandOtherBiologics/TransmissibleSpongiformEncephalopathiesAdvisoryCommittee/ucm231016.htm



October 28-29, 2010:

Transmissible Spongiform Encephalopathies Advisory Committee Meeting Document: APPENDIX A Supplemental technical information for the FDA Risk Assessment (PDF - 307KB) Posted: 10/26/2010 Roster of the Transmissible Spongiform Encephalopathies Advisory Committee Updated: 10/22/2010


http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/BloodVaccinesandOtherBiologics/TransmissibleSpongiformEncephalopathiesAdvisoryCommittee/UCM231019.pdf



Roster of the Transmissible Spongiform Encephalopathies Advisory Committee Updated: 10/22/2010


http://www.fda.gov/AdvisoryCommittees/CommitteesMeetingMaterials/BloodVaccinesandOtherBiologics/TransmissibleSpongiformEncephalopathiesAdvisoryCommittee/ucm129556.htm




Tuesday, September 14, 2010


Transmissible Spongiform Encephalopathies Advisory Committee; Notice of Meeting October 28 and 29, 2010 (COMMENT SUBMISSION)


----- Original Message -----


http://tseac.blogspot.com/2010/09/transmissible-spongiform_14.html




----- Original Message -----

From: Emery, Bryan (CBER)

To: CBER OCOD Consumer Account ; 'flounder9@verizon.net'

Sent: Friday, September 17, 2010 10:08 AM

Subject: FW: Transmissible Spongiform Encephalopathies Advisory Committee; Notice of Meeting October 28 and 29, 2010 (COMMENT SUBMISSION)

Hi Terry,

Thank you for your comments related to the Transmissible Spongiform Encephalopathy's Advisory Committee meeting on October 28-29, 2010.

Your comments will be provided to the Committee.

Thanks

Bryan Emery

Subject: Transmissible Spongiform Encephalopathies Advisory Committee; Notice of Meeting October 28 and 29, 2010 (COMMENT SUBMISSION)

Transmissible Spongiform Encephalopathies Advisory Committee; Notice of Meeting October 28 and 29, 2010

Contact Person: Bryan Emery or Rosanna Harvey, Center for Biologics Evaluation and Research (HFM-71), Food and Drug Administration, 1401 Rockville Pike, Rockville, MD 20852, 301-827-0314, or FDA Advisory Committee Information Line, 1-800-741-8138 (301-443-0572 in the Washington, DC area), code 3014512392.

http://edocket.access.gpo.gov/2010/2010-22805.htm



snip...end...full text ;


http://tseac.blogspot.com/2010/09/transmissible-spongiform_14.html




Monday, October 18, 2010


TSEAC Transmissible Spongiform Encephalopathies Advisory Committee Draft Agenda and Meeting Materials, Posted: 10/18/2010


http://tseac.blogspot.com/2010/10/tseac-transmissible-spongiform.html



__._,_.___



Tuesday, September 14, 2010


Transmissible Spongiform Encephalopathies Advisory Committee; Notice of Meeting October 28 and 29, 2010


http://tseac.blogspot.com/2010/09/transmissible-spongiform.html




----- Original Message -----

From: Emery, Bryan (CBER) To: 'Terry S. Singeltary Sr.'

Cc: Emery, Bryan (CBER)

Sent: Monday, January 24, 2011 7:35 AM

Subject: RE: October 28-29, 2010: Transmissible Spongiform Encephalopathies Advisory Committee

Hi Terry,

The minutes have not been my primary focus at this time but when they are completed they will be put online for the public. I have nothing to hide just very busy as of late. Thank you for your interest, I hope to see you again soon.

Thanks LCDR Bryan Emery

--------------------------------------------------------------------------------

From: Terry S. Singeltary Sr. [mailto:flounder9@verizon.net]

Sent: Wednesday, January 19, 2011 1:03 PM

To: Emery, Bryan (CBER)

Subject: October 28-29, 2010: Transmissible Spongiform Encephalopathies Advisory Committee

re-October 28-29, 2010: Transmissible Spongiform Encephalopathies Advisory Committee

Greetings Dr. Emery,

I am trying to locate the minutes or draft minutes of the October 28-29, 2010: Transmissible Spongiform Encephalopathies Advisory Committee meeting ???

seems they are long overdue to be put online.

can you please tell me when and if they are going to be made public ???

many thanks,

kindest regards, terry

Tuesday, January 18, 2011

Agent strain variation in human prion disease: insights from a molecular and pathological review of the National Institutes of Health series of experimentally transmitted disease

http://transmissiblespongiformencephalopathy.blogspot.com/2011/01/agent-strain-variation-in-human-prion.html




sadly, by only trying to reduce exposure from only nvCJD, they are seriously missing the bigger picture. hell, now we have mixtures of different phenotypes in one species, what about transmission of the TSE agent via mulitple phenotypes from one donor ??? transmission studies ??? etc. .......they missed the boat a long time ago. i believe i said in 2001 ;

"I am beginning to think that the endless attempt to track down and ban, potentia.1 victims from known BSE Countries from giving blood will be futile. You would have to ban everyone on the Globe eventually? AS well, I think we MUST ACT SWIFTLY to find blood test for TSE's, whether it be blood test, urine test, .eyelid test, anything at whatever cost, we need a test FAST."


http://www.fda.gov/ohrms/dockets/ac/01/slides/3681s2_09.pdf



end...tss




Saturday, September 5, 2009


TSEAC MEETING FEBRUARY 12, 2004 THE BAXTER STUDY GSS


http://tseac.blogspot.com/2009/09/tseac-meeting-february-12-2004-baxter.html




From: Terry S. Singeltary Sr.

To: FREAS@CBER.FDA.GOV

Cc: william.freas@fda.hhs.gov ; rosanna.harvey@fda.hhs.gov

Sent: Friday, December 01, 2006 2:59 PM

Subject: Re: TSE advisory committee for the meeting December 15, 2006 [TSS SUBMISSION PART III]

page 1 starts on page 13, then come back to page 1 to finish.....tss


http://www.regulations.gov/fdmspublic/ContentViewer?objectId=09000064801f3413&disposition=attachment&contentType=msw8




PDF]Freas, William TSS SUBMISSION

File Format: PDF/Adobe Acrobat -

Page 1. J Freas, William From: Sent: To: Subject: Terry S. Singeltary

Sr. [flounder@wt.net] Monday, January 08,200l 3:03 PM freas ...


http://www.fda.gov/ohrms/dockets/ac/01/slides/3681s2_09.pdf




World's first blood test for vCJD developed in MRC lab


Thursday 3 February 2011


The world's first accurate blood test for variant Creutzfeldt-Jakob disease (vCJD) has been developed by Medical Research Council (MRC) scientists. The prototype, which is 100,000 times more sensitive than any previous attempt, could transform the diagnosis and screening of the brain disease.

Variant CJD, the human form of BSE (or mad cow disease) first emerged in 1995. The disease, which affects the brain, is believed to have passed from cattle to humans through infected food. It causes personality change, loss of body function, and eventually death.

The research team from the MRC Prion Unit, based at University College London, working with the National Prion Clinic at the National Hospital for Neurology and Neurosurgery (NHNN) tested 190 blood samples, including 21 from individuals known to have vCJD. The blood test was able to detect blood spiked with a dilution of vCJD to within one part per ten billion - 100,000 times more sensitive than any other method developed so far.

Prions, the infectious proteins which cause vCJD and other fatal prion diseases, can inhabit a person's body for up to 50 years before presenting symptoms. During this time there is a chance a carrier of vCJD infection could pass on the infection to others, for example through blood transfusion or even through surgical and medical instruments as prions can easily attach onto metal surfaces.

A widely available, accurate blood test would enable people to be diagnosed earlier and could also help identify carriers of the disease. This would help measure how widespread the prion infection is in the general population and identify those who are at risk of passing on the infection to others.

Lead author Dr Graham Jackson, Programme Leader at the MRC Prion Unit, said:

"This test comes at the end of many years of meticulous, painstaking research in our Unit and the NHS National Prion Clinic. Although further larger studies are needed to confirm its effectiveness, it's the best hope yet of a successful early diagnostic test for the disease. This test could potentially go on to allow blood services to screen the population for vCJD infection, assess how many people in the UK are silent carriers and prevent onward transmission of the disease."

Professor John Collinge, Director of the MRC Prion Unit, said:

"One of the reasons that vCJD is such a dreaded disease and has caused such disruption and expense to health services is the lack of knowledge of who is and who is not a carrier of this infection. The next step will be to test anonymously several thousand blood donors from a country unaffected by BSE in order to gain a better idea of how the test fares in practice. Longer term studies will also be needed to assess what proportion of individuals who test positive for prion infection will then go on to develop the disease later in life.

"The MRC Prion Unit's research with the NHS National Prion Clinic to improve early diagnosis is an essential part of the wider MRC strategy to develop better treatments for patients. For this to develop, it will be crucial for clinicians to be able to offer treatment before extensive irreversible damage to the brain has occurred. At the moment, a firm diagnosis of vCJD can usually be made only once serious symptoms of the disease have developed which indicate extensive damage to the brain."

The study 'A blood-based assay for the detection of vCJD prion infection' is published today in the journal The Lancet.

Ends

Notes to editors:

To arrange an interview with the researchers of this paper, please call the MRC Press Office on 0207 395 2345.

For almost 100 years the Medical Research Council has improved the health of people in the UK and around the world by supporting the highest quality science. The MRC invests in world-class scientists. It has produced 29 Nobel Prize winners and sustains a flourishing environment for internationally recognised research. The MRC focuses on making an impact and provides the financial muscle and scientific expertise behind medical breakthroughs, including one of the first antibiotics penicillin, the structure of DNA and the lethal link between smoking and cancer. Today MRC funded scientists tackle research into the major health challenges of the 21st century. www.mrc.ac.uk

While the number of vCJD samples available for analysis was inherently small, and to date only a small number of healthy donors has been studied, analysis of this blinded panel indicated an assay sensitivity for vCJD of over 71% (15/21, CI 48-89%) and a specificity of 100% (0/169, CI 98-100%).

The NHNN forms part of University College London Hospitals NHS Foundation Trust, one of the largest NHS trusts in the United Kingdom providing first-class acute and specialist services. The Trust is committed to research and development and forms part of UCL Partners which in March 2009 was officially designated as one of the UK's first academic health science centres by the Department of Health. UCLH works closely with UCL, translating research into treatments for patients. www.uclh.nhs.uk

http://www.mrc.ac.uk/Newspublications/News/MRC007683




Wednesday, February 2, 2011


Detection of prion infection in variant Creutzfeldt-Jakob disease: a blood-based assay


http://transmissiblespongiformencephalopathy.blogspot.com/2011/02/detection-of-prion-infection-in-variant.html




Transmissible Spongiform encephalopathy (TSE) animal and human TSE in North America

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.


page 114 ;


http://ww2.isid.org/Downloads/14th_ICID_ISE_Abstracts.pdf




International Society for Infectious Diseases Web: http://www.isid.org/



please see full text ;


http://transmissiblespongiformencephalopathy.blogspot.com/




Seven main threats for the future linked to prions

The NeuroPrion network has identified 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




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




Saturday, January 29, 2011

Atypical L-Type Bovine Spongiform Encephalopathy (L-BSE) Transmission to Cynomolgus Macaques, a Non-Human Primate

Jpn. J. Infect. Dis., 64 (1), 81-84, 2011


http://transmissiblespongiformencephalopathy.blogspot.com/2011/01/atypical-l-type-bovine-spongiform.html




Tuesday, November 02, 2010

BSE - ATYPICAL LESION DISTRIBUTION (RBSE 92-21367) statutory (obex only) diagnostic criteria CVL 1992


http://bse-atypical.blogspot.com/2010/11/bse-atypical-lesion-distribution-rbse.html




Wednesday, July 28, 2010

Atypical prion proteins and IBNC in cattle DEFRA project code SE1796 FOIA Final report


http://bse-atypical.blogspot.com/2010/07/atypical-prion-proteins-and-ibnc-in.html




Thursday, November 18, 2010


UNITED STATES OF AMERICA VS GALEN J. NIEHUES FAKED MAD COW FEED TEST ON 92 BSE INSPECTION REPORTS FOR APPROXIMATELY 100 CATTLE OPERATIONS


http://bse-atypical.blogspot.com/2010/11/united-states-of-america-vs-galen-j.html




Friday, August 27, 2010


NEW ATYPICAL NOR-98 SCRAPIE CASE DETECTED IDAHO NOW 5 CASES DOCUMENTED 2010


http://nor-98.blogspot.com/2010/08/new-atypical-nor-98-scrapie-case.html




Thursday, August 19, 2010

SCRAPIE CANADA UPDATE Current as of 2010-07-31 The following table lists sheep flocks and/or goat herds confirmed to be infected with scrapie in Canada in 2010.

Current as of: 2010-07-31


http://nor-98.blogspot.com/2010/08/scrapie-canada-update-current-as-of.html




the OIE and the USDA systematically changed the science with the BSE MRR policy, and put everyone around the globe at risk by taking us back to ground zero 1984-1985 kent bse cow.

Saturday, June 19, 2010

U.S. DENIED UPGRADED BSE STATUS FROM OIE


http://usdameatexport.blogspot.com/2010/06/us-denied-upgraded-bse-status-from-oie.html




Tuesday, January 25, 2011

Generation of a new form of human PrPSc in vitro by inter-species transmission from cervids prions


http://chronic-wasting-disease.blogspot.com/2011/01/generation-of-new-form-of-human-prpsc.html




Wednesday, September 08, 2010

CWD PRION CONGRESS SEPTEMBER 8-11 2010


http://chronic-wasting-disease.blogspot.com/2010/09/cwd-prion-2010.html




Friday, February 04, 2011

NMLB and USDA allow scrapie prion infected mutton to enter food chain on the Navajo Reservation in New Mexico


http://scrapie-usa.blogspot.com/2011/02/nmlb-and-usda-allow-scrapie-prion.html




Wednesday, January 19, 2011

EFSA and ECDC review scientific evidence on possible links between TSEs in animals and humans Webnachricht 19 Januar 2011


http://transmissiblespongiformencephalopathy.blogspot.com/2011/01/efsa-and-ecdc-review-scientific.html




Tuesday, January 18, 2011

Agent strain variation in human prion disease: insights from a molecular and pathological review of the National Institutes of Health series of experimentally transmitted disease


http://transmissiblespongiformencephalopathy.blogspot.com/2011/01/agent-strain-variation-in-human-prion.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




Sunday, January 30, 2011

Vaccines and Transmissible Spongiform Encephalopathy the Prion Disease, what if ?

COMMERCIAL IN CONFIDENCE


http://transmissiblespongiformencephalopathy.blogspot.com/2011/01/vaccines-and-transmissible-spongiform.html




strictly NOT private and confidential $$$


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




Monday, September 13, 2010


atypical BSE strains and sporadic CJD strains, is there a connection and why shouldn't there be $


http://bse-atypical.blogspot.com/2010/09/atypical-bse-strains-and-sporadic-cjd.html




Sunday, August 15, 2010


ATYPICAL BSE NOW LINKED TO CAUSING SPORADIC CJD OVERSEAS Commonwealth of Australia


http://bse-atypical.blogspot.com/2010/08/atypical-bse-now-linked-to-causing.html




Thursday, July 08, 2010


GLOBAL CLUSTERS OF CREUTZFELDT JAKOB DISEASE - A REVIEW 2010


http://creutzfeldt-jakob-disease.blogspot.com/2010/07/global-clusters-of-creutzfeldt-jakob.html





DID EVERYONE THAT LOST A LOVED ONE FILL OUT THEIR CJD QUESIONNAIRE FROM THE CDC AND OR THE CJD FOUNDATION ???


Friday, November 30, 2007


CJD QUESTIONNAIRE USA CWRU AND CJD FOUNDATION


http://cjdquestionnaire.blogspot.com/




TSS