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Ministers' Deputies b. Draft Recommendation Rec(2001).. of the Committee of Ministers to member States on the prevention of the possible transmission of variant Creutzfeldt-Jakob Disease (vCJD) by blood transfusion - Explanatory report.
Explanatory report to Recommendation Rec(2001).. of the Committee of Ministers to member States on the prevention of the possible transmission of variant Creutzfeldt-Jakob Disease (vCJD) by blood transfusion
Creutzfeldt-Jakob Disease in its classical form was first described in the 1920s. It is one of a group of diseases known as transmissible spongiform encephalopathies (TSEs) which can occur in people or animals. The diseases are characterised by degeneration of the nervous system and are invariably fatal.
Early in 1996, the United Kingdom National CJD Surveillance Unit based in Edinburgh, identified a form of CJD that differed from previously recognised types of the disease.
- Patients affected are usually younger, the median age of onset being 28 years. In classical CJD, the average age of onset is 65 years, some cases do occur under 50 years of age.
- The presenting symptoms are different and the clinical course is longer. Patients usually present with psychiatric or sensory disturbances or a combination of both. These early non-specific clinical signs may last for several months and the diagnoses of vCJD may not be suspected for some time. The median duration of the illness is 14 months. In contrast, classical CJD has a fast clinical course with rapid onset of progressive pre-senile dementia, myoclonus and progressive motor dysfunction, with death occurring within a few months.
- The neuropathological changes in the brain show a consistently different pattern of amyloid-like plaque inclusions and is characteristic for vCJD.
The disease was initially labelled new variant CJD (nvCJD) and is now known as variant CJD (vCJD).
The precise nature of the causative agent for vCJD is not known but research indicates that it is most likely to be an acquired prion disease caused by exposure to Bovine Spongiform Encephalopathy (BSE) or a BSE-like agent.
Incidence: From the beginning of 1996 to 4 September 2000 the UK has reported 82 cases (69 confirmed and 13 probable). France has 3 confirmed cases. Republic of Ireland has 1 confirmed case.
The treatment of vCJD is symptomatic, there is no
cure and no known means of prevention at present.
No tests are available at present to screen for vCJD.
The diagnosis is usually a clinical one and is confirmed by
brain biopsy or autopsy. It has now been established beyond reasonable doubt that the transmissible agent for vCJD is indistinguishable from that of BSE and that vCJD results most likely from the exposure to bovine products derived from BSE infected cattle.
The biology of vCJD, with involvement of the lymphoreticular system in the infective process (tonsils, lymph nodes, spleen and appendix) is different from classical CJD and therefore may present an increased theoretical risk of transmission of the infective agent by transfusion, via the lymphocytes.
However, because of the different biological characteristics of vCJD, precautionary measures to minimise this theoretical risk of transfusion transmission may need to be considered. When considering any precautionary measure to protect the blood supply, the balance of risks between compromising the adequacy of the blood supply and minimising a theoretical risk needs to be considered. In addition, its value and necessity should be discussed, in which both the benefits for the public health as well as the cost-benefit ratio are considered.
The Committee of Proprietary Medicinal Products (CPMP)
● Recall
In February 1998, CPMP recommended as a precautionary measure that it would be prudent to withdraw batches of plasma derived medicinal products from the market if a donor to a plasma pool is subsequently strongly suspected, by a recognised reference centre, of having vCJD. However, consequences for essential medicinal products where alternatives are not available will need careful consideration by national authorities. (Annex IV to CPMP - February 1998 Press Release - CPMP/201/98).
● Albumin as an excipient (in vaccines)
Since a recall involving albumin used as an excipient has the potential to cause major supply difficulties for essential products, manufacturers should avoid using, as an excipient, albumin derived from countries where a number of cases of vCJD have occurred.
● Rationale
Knowledge of other TSE agents suggest that transmission of vCJD by medicinal products derived from human blood or plasma is very unlikely. However, the different biological characteristics of vCJD may theoretically increase the likelihood of transfusion transmission. Therefore, until more is known about the vCJD infective agent it is considered prudent to take extra precautionary measures to minimise this theoretical risk.
UK Precautionary Measures
● Use of non-UK sourced plasma and blood products
The UK Committee on Safety of Medicines (CSM) advised in May 1998 that manufactured plasma derivatives should not be sourced from UK plasma until such time as there is a screening test for vCJD and fractionation processes can be validated for clearance of the vCJD agent. All plasma derivatives manufactured in the UK are now made from non-UK plasma.
● Use of pre-storage leucodepleted blood for all transfusions
The Spongiform Encephalopathy Advisory Committee on TSEs (SEAC) had commissioned a risk assessment from Det Norske Veritas, following which they advised in June 1998 that as a precautionary measure the use of leucodepletion for all blood and blood components destined for transfusion should be implemented as soon as practically possible.
100% leucodepletion of all blood and blood components achieved by 31 October 1999.
● Surveillance System
All new cases of CJD (all types) are notified to the CJD Surveillance Unit in Edinburgh to ensure early action to trace and withdraw any blood donations which a sufferer of vCJD may have made.
● Potential Donors
Measures are being taken to prevent donations from recipients of blood donated by individuals who subsequently developed vCJD from entering the blood supply.
● Blood Transfusion Recipients
Consideration may need to be given by UK Authorities to the exclusion of blood donors who have received transfusions of labile blood components in the past. Care will need to be taken to demonstrate that this measure will not seriously compromise the blood supply.
● Appropriate Use of Blood
The UK Chief Medical Officers launched an initiative in 1998 to promote the “Better Use of Blood”, to minimise unnecessary exposure of patients to blood transfusion.
Precautionary measures taken by other European countries
● By December 2000, Austria, France, Germany and Italy had imposed a ban on blood donations from anyone who has spent six or more cumulative months in Britain from 1 January 1980 – 31 December 1996 to minimise the theoretical risk of transmitting vCJD by blood transfusion.
USA FDA and the Canadian Health Protection Branch Precautionary Measures
● In August 1999, the FDA and the Canadian Health Protection Branch imposed a ban on blood donations from anyone who has spent six or more cumulative months in Britain from 1 January 1980 – 31 December 1996 to minimise the theoretical risk of transmitting vCJD by blood transfusion. The exclusion dates coincide with the time when exposure to beef contaminated with BSE was considered to be at its peak in the UK.
In August 2000, the Canadian Health Protection Branch imposed the same ban on blood donations from anyone who has spent a cumulative total of six months or more in France from 1 January 1980 – 31 December 1996.
European Commission
In February 2000, the Scientific Committee on Medicinal Products and Medical Devices (SCMPMD) published an update on their opinion on the risk quantification for CJD transmission via substances of human origin. The information contained in this document has been taken into account in formulating the Council of Europe Recommendation on vCJD.
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