Abstract
The identification in the UK of 4 v-CJD infected patients thought to be due to the use of transfused Red Blood Cell units prepared from blood of donors incubating v-CJD raised major concerns in transfusion medicine. The demonstration of leucocyte associated infectivity using various animal models of TSE infection led to the implementation of systematic leuco-depletion (LD) of Red Blood cells concentrates (RBCs) in a number of countries. In the same models, plasma also demonstrated a significant level of infectivity which raised questions on the impact of LD on the v-CJD transmission risk. The recent development of filters combining LD and the capture of non-leucocyte associated prion infectivity meant a comparison of the benefits of LD alone versus LD/prion-reduction filters (LD/PR) on blood-borne TSE transmission could be made. Due to the similarity of blood/plasma volumes to human transfusion medicine an experimental TSE sheep model was used to characterize the abilities of whole blood, RBCs, plasma and buffy-coat to transmit the disease through the transfusion route. The impact of a standard RBCs LD filter and of two different RBCs LD/PR prototype filters on the disease transmission was then measured. Homologous recipients transfused with whole-blood, buffy-coat and RBCs developed the disease with 100% efficiency. Conversely, plasma, when intravenously administered resulted in an inconstant infection of the recipients and no disease transmission was observed in sheep that received cryo-precipitated fraction or supernatant obtained from infectious plasma. Despite their high efficacy, LD and LD/PR filtration of the Red Blood Cells concentrate did not provide absolute protection from infection. These results support the view that leuco-depletion strongly mitigates the v-CJD blood borne transmission risk and provide information about the relative benefits of prion reduction filters.
Highlights
Transmissible spongiform encephalopathies (TSE), or prion diseases, are fatal neurodegenerative disorders naturally occurring in sheep, cattle, and humans (Creutzfeldt-Jakob disease - CJD).In humans, CJD is a rare disease that usually occurs as either a sporadic (s-CJD), familial or genetic form
The results obtained in this experiment using the PG127 sheep infection model indicated that the transfusion of standard Red Blood cells concentrates (RBCs), prepared using 400 mL of blood, transmitted the disease with 100% efficiency compared to only one out of the five recipients of the leuco-depleted red blood cell concentrates (LD-RBCs)
This efficacy of disease transmission by the transfusion of LD-RBCs was lower than the one reported in the same model using 200 mL of whole blood [17]
Summary
Transmissible spongiform encephalopathies (TSE), or prion diseases, are fatal neurodegenerative disorders naturally occurring in sheep (scrapie), cattle (bovine spongiform encephalopathy BSE), and humans (Creutzfeldt-Jakob disease - CJD).In humans, CJD is a rare disease (about 1 case per million and per year) that usually occurs as either a sporadic (s-CJD), familial or genetic form. Low levels of infectivity could be detected in different rodent experimental models, large scale retrospective epidemiological studies failed to demonstrate any association between the occurrence of CJD and transfusion of blood/plasma or the administration of plasma derived products [2,3,4,5]. These elements led to the contention that blood borne CJD inter-human transmission risk was negligible
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