Variant Creutzfeldt-Jakob disease (vCJD) is a human
prion disease resulting from zoonotic transmission of
bovine spongiform encephalopathy (BSE). Documented cases of vCJD transmission by
blood transfusion necessitate on-going risk reduction measures to protect blood supplies, such as leucodepletion (removal of white blood cells, WBCs). This study set out to determine the risks of
prion transmission by transfusion of labile blood components (red blood cells, platelets, plasma) commonly used in human medicine, and the effectiveness of leucodepletion in preventing
infection, using BSE-infected sheep as a model. All components were capable of transmitting
prion disease when donors were in the preclinical phase of
infection, with the highest rates of
infection in recipients of whole blood and buffy coat, and the lowest in recipients of plasma. Leucodepletion of components (<106 WBCs/unit) resulted in significantly lower transmission rates, but did not completely prevent transmission by any component. Donor PRNP genotype at
codon 141, which is associated with variation in incubation period, also had a significant effect on transfusion transmission rates. A sensitive
protein misfolding cyclic amplification (PMCA) assay, applied to longitudinal series of blood samples, identified infected sheep from 4 months post
infection. However, in donor sheep (orally infected), the onset of detection of PrPSc in blood was much more variable, and generally later, compared to recipients (intravenous
infection). This shows that the route and method of
infection may profoundly affect the period during which an individual is infectious, and the test sensitivity required for reliable preclinical diagnosis, both of which have important implications for disease control. Our results emphasize that
blood transfusion can be a highly efficient route of transmission for
prion diseases. Given current uncertainties over the prevalence of asymptomatic vCJD carriers, this argues for the maintenance and improvement of current measures to reduce the risk of transmission by blood products.