Preclinical transmission of prions by blood transfusion is influenced by donor genotype and route of infection

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...

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Published in:PLoS pathogens 2021-02, Vol.17 (2), p.e1009276
Main Authors: Salamat, M Khalid F, Blanco, A Richard Alejo, McCutcheon, Sandra, Tan, Kyle B C, Stewart, Paula, Brown, Helen, Smith, Allister, de Wolf, Christopher, Groschup, Martin H, Becher, Dietmar, Andréoletti, Olivier, Turner, Marc, Manson, Jean C, Houston, E Fiona
Format: Article
Language:English
Subjects:
Animal models
Biology and Life Sciences
Blood
Blood & organ donations
Blood cells
Blood platelets
Blood products
Blood transfusion
Blood transfusions
Bovine spongiform encephalopathy
BSE
Cattle
Creutzfeldt-Jakob disease
Epidemiology
Genotype & phenotype
Genotypes
Incubation
Infections
Infectivity
Kuru
Leukocytes
Life Sciences
Medicine and Health Sciences
Plasma
Prion protein
Prions
Protein folding
Safety measures
Sheep
Transfusion
White blood cells
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Blanco, A Richard Alejo
McCutcheon, Sandra
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Becher, Dietmar
Andréoletti, Olivier
Turner, Marc
Manson, Jean C
Houston, E Fiona
description 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 (
doi_str_mv 10.1371/JOURNAL.PPAT.1009276
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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 (&lt;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. 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1553-7366
1553-7374
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recordid cdi_plos_journals_2501882303
source Publicly Available Content Database; PubMed Central
subjects Animal models
Biology and Life Sciences
Blood
Blood & organ donations
Blood cells
Blood platelets
Blood products
Blood transfusion
Blood transfusions
Bovine spongiform encephalopathy
BSE
Cattle
Creutzfeldt-Jakob disease
Epidemiology
Genotype & phenotype
Genotypes
Incubation
Infections
Infectivity
Kuru
Leukocytes
Life Sciences
Medicine and Health Sciences
Plasma
Prion protein
Prions
Protein folding
Safety measures
Sheep
Transfusion
White blood cells
title Preclinical transmission of prions by blood transfusion is influenced by donor genotype and route of infection
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