title: Impact of leucocyte depletion and prion reduction filters on TSE blood borne transmission.
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.
authors.affiliation: UMR INRA ENVT 1225, Interactions Hôte Agent Pathogène, Ecole Nationale Vétérinaire de Toulouse, Toulouse, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Lacroux
authors.forename: Daisy
authors.initials: D
authors.lastname: Bougard
authors.forename: Claire
authors.initials: C
authors.lastname: Litaise
authors.forename: Hugh
authors.initials: H
authors.lastname: Simmons
authors.forename: Fabien
authors.initials: F
authors.lastname: Corbiere
authors.forename: Dominique
authors.initials: D
authors.lastname: Dernis
authors.forename: René
authors.initials: R
authors.lastname: Tardivel
authors.forename: Nathalie
authors.initials: N
authors.lastname: Morel
authors.forename: Stephanie
authors.initials: S
authors.lastname: Simon
authors.forename: Séverine
authors.initials: S
authors.lastname: Lugan
authors.forename: Pierrette
authors.initials: P
authors.lastname: Costes
authors.forename: Jean Louis
authors.initials: JL
authors.lastname: Weisbecker
authors.forename: François
authors.initials: F
authors.lastname: Schelcher
authors.forename: Jacques
authors.initials: J
authors.lastname: Grassi
authors.forename: Joliette
authors.initials: J
authors.lastname: Coste
authors.forename: Olivier
authors.initials: O
authors.lastname: Andréoletti
mesh_terms: D000818:Animals; D017848:Blood-Borne Pathogens; D015153:Blotting, Western; D007150:Immunohistochemistry; D047589:Leukocyte Reduction Procedures; D017096:Prion Diseases / Q000635:transmission*; D011328:Prions / Q000302:isolation & purification*; D012756:Sheep
chemical_list: D011328:Prions