On July 22, 2004 the United Kingdom (U.K.) Department of Health identified a second case of variant Creutzfeldt-Jakob (vCJD) suspected to have been acquired by transfusion of whole blood contaminated by the vCJD agent. Although the patient had no symptoms of vCJD and died of causes unrelated to vCJD, a post mortem examination revealed the evidence of vCJD infection in the spleen. The source of the infection is thought to be a blood transfusion the patient received in 1999 from a donor who later died of vCJD. The patient was identified as a result of a vCJD surveillance program to monitor all recipients of suspected blood transfusions and blood products. The first suspected case of transfusion transmission of vCJD was previously reported in December 2003. In that case, both the donor and the recipient died of vCJD. (See "WFH Statement on Transmission of vCJD by Transfusion" dated December 19, 2003.) Together, the two cases most certainly confirm the hypothesis that vCJD can be transmitted in humans by blood or blood components.
The second case is also significant because of the type of genetic variation of normal prion material found in the patient’s brain. To date, all reported cases of vCJD have been found to be M/M homozygous at codon 129 of the normal prion gene (a genetic variation found in a minority of the UK population). As a result of these observations, some investigators have postulated that individuals with the homozygous genetic variation are more susceptible to vCJD. The most recent case, however, is reported to be M/V heterozygous for the prion gene, a more common variation. The identification of the new case suggests that the heterozygote M/V variation is also susceptible to transmission by the intravenous route, although evidence has not been found to show that these individuals are susceptible to infection by an oral route, e.g. eating contaminated beef (the primary route of infection for patients with vCJD).
Discussion
It is reasonable to accept these cases as confirmation of the risk of blood transmission of vCJD. This confirmation is not unexpected from the results of a number of animal experiments, including transmission in sheep – the subject of previous WFH TSE Bulletins. The risk of such occurrences appears to be predominately a risk for recipients of blood components collected in the U.K. Donor screening procedures and blood banking policies initiated in countries throughout the world appear to be appropriate to reduce the risk of such transmissions to a minimum.
Presently, clotting factor concentrates manufactured from plasma obtained outside the U.K. appear to carry a very low risk of transmission of vCJD because of the exclusion of potential donors incubating vCJD and the reduction of potential agents by the manufacturing processes. Continued vigilance is important to identify any changes in the level of suspected risk. In particular, authorities responsible for hemophilia care should be aware that the level of risk minimization for hemophilia products is heavily dependant on the nature of the manufacturing process and its ability to purify the coagulation factors to as high a level of purity as possible. Donor deferral measures are known to only decrease risk by about one log, whereas reductions of eight logs of TSE are demonstrable for very high purity products. Recombinant products manufactured without human or bovine constituents are devoid of TSE risk.
WFH will continue to monitor this situation and we shall keep you informed.
July 28, 2004
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