Updated: August 6, 2002
Transmission of prion diseases by blood transfusion
An electronic version of a paper entitled "Transmission of prion diseases by blood transfusion" by Nora Hunter and colleagues of the Institute for Animal Health in the UK is available as a PDF document, and will be published in a fall issue of the Journal of General Virology. This paper updates the status of ongoing studies on the transmissibility of variant Creutzfeldt-Jakob disease (vCJD) by blood transfusion in sheep. In brief, blood obtained from sheep was experimentally infected with BSE (bovine spongiform encephalopathy) and blood from sheep with naturally acquired scrapie were transfused into healthy sheep that had not previously been exposed to these agents. Although the full experiment will take at least five years to complete, 2 of 24 (8%) healthy sheep that received blood transfusions from the infected sheep have already contracted BSE, and 4 of 21 (20%) have developed scrapie. These findings further support the hypothesis that spongiform encephalopathies (which include BSE, scrapie, and vCJD) can be transmitted by blood transfusion. A preliminary report of the study was published in the September 2000 journal Lancet noting that 1 of 19 sheep that received whole blood collected from a donor sheep incubating BSE developed the disease. It should be noted, however, that sheep used as recipients of the donated blood were specially selected for their genetic susceptibility to prion diseases (prion diseases are diseases caused by abnormal prion proteins, including BSE, scrapie, and vCJD). The study also found that blood donations were infectious even when taken from infected but asymptomatic (without symptoms) animals.
In vCJD (but not sporadic CJD), prion protein has been found in tonsils and spleen, and has led to tonsillar biopsy as a tool for diagnosing suspected cases of vCJD. In contrast, the authors of this study report that very few abnormal prions were detected outside the brain in the sheep that were infected through blood transfusion. The authors speculate that if humans were secondarily infected with vCJD from blood transfusions, biopsies might not be as useful as in primary cases of vCJD acquired directly from BSE-infected cattle.
Although these findings support a growing body of evidence that it may be possible to transmit vCJD in experimental animals, it does not change implications for persons receiving plasma derivatives. BSE and vCJD are confined to certain parts of Europe, predominantly the UK. No concentrates are now made from UK-derived plasma, which undoubtedly constitutes the greatest risk. Most countries defer donors who have resided for some time in high-risk areas such as the UK. Several studies have shown that a number of purification steps used for the manufacture of clotting factor concentrates remove large amounts of infectious material from plasma, far greater amounts than have been found in blood samples of both persons and animals with the disease. It is thought that any infectious material remaining in clotting factor concentrates would not be enough to cause disease. It is important to remember that, in spite of extensive searches, public health authorities have not found a case of either classical or variant CJD in a person with hemophilia but continue to search vigorously.
The WFH Task Force will continue to monitor developments in order to keep you informed.
Updated: July 10, 2002
EMEA Meeting on TSEs
The European Agency for the Evaluation of Medicinal Products (EMEA) convened an expert workshop on human TSEs (transmissible spongiform encephalopathies) and medicinal products at their European headquarters in London’s Canary Wharf on June 19 th and 20 th. This meeting was chaired by Professor Jean-Hugues Trouvin, of the Agence Française de Securité Sanitaire des Produits de Santé. The two-day meeting included presentations from invited speakers from around the world, including scientists and clinicians, representatives of the regulatory authorities and patient organisations. This open meeting was followed by a closed meeting of the TSE Expert Group of the EMEA Group on June 21 st, which formulates opinion on such matters as safety of plasma products and whether additional steps need to be taken to minimise the possibility of transmission of prions through the use of biological materials such as whole blood, plasma and urine. A report will be published in due course and this will be available through the EMEA website ( http://www.emea.eu.int ).
For a summary, click on EMEA meeting on TSEs (PDF)
London , June 19-20, 2002
Dr. Paul Giangrande, Oxford Haemophilia Centre
Updated: January 6, 2002
Predicting the number of cases of variant Creutzfeldt-Jakob disease in the United Kingdom
An article by G.F. Medley in the November 23 issue of Science outlined new studies that attempt to predict patterns of variant Creutzfeldt-Jakob disease in the United Kingdom. Using statistical approaches to predict future numbers of cases, the two studies’ predictions range from several hundred (Valleron et al.) to several hundred thousand (Huillard d’Aignaux et al.). The author uses differences between two studies to discuss the wide range of expected cases, and also discusses the pitfalls of various statistical models. He suggests that predictions may be valid for pointing out and clarifying the factors which define and delineate an epidemic.
The article can be accessed from the Science web site at http://www.sciencemag.org.
Updated: December 7, 2001
Revised TSE Task Force Bulletin 2
The World Federation of Hemophilia’s Task Force on Transmissible Spongiform Encephalopathies (TSEs) has published a revised edition of Variant Creutzfeldt-Jakob Disease and Haemophilia: A Risk Assessment of Plasma-derived Products. The revised bulletin includes new information on donor deferral measures and the behaviour of the classical CJD agent during factor VIII fractionation processes. The new information highlights the fact that the U.S. Food and Drug Administration (FDA) has acknowledged the ability of plasma fractionation processes, including the techniques used to manufacture FVIII and FIX, to eliminate the agents associated with TSEs. The FDA’s current draft guidance exempts European source plasma donors (with the exception of the U.K. and France) from deferral measures.
Revised Bulletin 2 - vCJD and Haemophilia - A Risk Assessment of Plasma-derived Products (PDF file)
Updated: September 20, 2001
New Developments
- One case of bovine spongiform encephalopathy (BSE) has been identified in Japan.
- A new case of variant Creutzfeldt-Jakob disease (vCJD) has been identified in France, bringing the total number of cases to four.
It is important to note that no cases of vCJD have yet been attributed to blood or blood products.
New FDA Guidance on Donor Deferrals
On August 27, 2001, the U.S. Food and Drug Administration issued draft revised guidance intended to further reduce the risk of transmission of vCJD to recipients of blood and blood products.
The proposed revised guidance includes changes that would expand the deferrals of donors who have lived or travelled in the U.K. and Europe. Specific changes to the previous guidance that are being proposed include:
For implementation by May 31, 2002:
- Deferral of donors who have spent three or more cumulative months in the U.K. from the beginning of 1980 through the end of 1996.
- Deferral of donors who have spent five cumulative years or more in France from 1980 to the present.
- Deferral of current or former U.S. military personnel who have lived for six months or more at U.S. military bases in Europe from 1980 to 1996.
- Deferral of donors who have received a blood transfusion in the U.K. between 1980 and the present.
For implementation by October 31, 2002:
- Deferral of donors who have spent a cumulative total period of five years or more in Europe from 1980 to the present.
The new draft revised guidance can be obtained on FDA’s web site at: http://www.fda.gov/cber/guidelines.htm.
Summary of Donor Deferral Measures
Responses to the possible threat of vCJD have been varied among countries. Policies on donor deferrals made by regulatory bodies such as the FDA differ from country to country. This has led to disharmony in donor screening policies. On behalf of the WFH TSE Task Force, Dr. Albert Farrugia has prepared a summary of current donor deferral measures. Please note that the information is subject to change and this should not be regarded as a definitive list.
Bulletin 3 - Donor Deferral Measures (November 15, 2001)
Updated: July 23, 2001
Summary of FDA TSE Advisory Committee meeting on vCJD donor deferrals. (Reprinted from the June 29, 2001 edition of the ABC Newsletters, with permission from America"s Blood Centers.)
Updated: June 28, 2001
On June 28-29, the TSE Advisory Committee of the FDA met to discuss stricter donor deferrals for people who had spent significant time in the U.K. and Europe.
WFH Executive Director Line Robillard presented a statement to the FDA Committee.
Updated: April 18, 2001
The WFH Task Force on TSEs met in March to review developments in Europe and the United States of America. Regulatory agencies in Europe continue to work to establish uniform guidelines for reducing the risk of TSEs.
Active surveillance for possible cases of vCJD continues in both Europe and North America. As yet, no case of vCJD has been identified that was shown to be transmitted by blood or blood products and no case of vCJD or classical CJD has been found in a person with hemophilia despite extensive searches.
Updated: March 15, 2001
A report of the TSE experts of the European Agency for the Evaluation of Medicinal Products (EMEA) is expected to be presented in March.
In the United States, the American Red Cross (ARC) has proposed stricter restrictions on U.S. blood donors who have spent time in Europe than those proposed by the Food and Drug Administration’s TSE Advisory Committee in January. ARC supports tightening the deferral period to less than six months in the U.K. and extending the exposure period to between 1980 and the present. Furthermore ARC supports the expansion of the existing U.K. deferral to included France and Western Europe. The Red Cross estimates that expanding the deferral criteria will reduce the current number of blood donors in the range of 5 to 6 percent.
This is intended to provide information only. The World Federation of Hemophilia does not engage in the practice of medicine and under no circumstances recommends particular treatment for specific individuals. In the case of vCJD and individual medical inquiries, the WFH suggests that further details should be sought from personal doctors or hemophilia centre staff.
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