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Prion infections, blood and transfusions

Abstract

Prion infections lead to invariably fatal diseases of the CNS, including Creutzfeldt–Jakob disease (CJD) in humans, bovine spongiform encephalopathy (BSE), and scrapie in sheep. There have been hundreds of instances in which prions have been transmitted iatrogenically among humans, usually through neurosurgical procedures or administration of pituitary tissue extracts. Prions have not generally been regarded as blood-borne infectious agents, and case–control studies have failed to identify CJD in transfusion recipients. Previous understanding was, however, questioned by reports of prion infections in three recipients of blood donated by individuals who subsequently developed variant CJD. On reflection, hematogenic prion transmission does not come as a surprise, as involvement of extracerebral compartments such as lymphoid organs and skeletal muscle is common in most prion infections, and prions have been recovered from the blood of rodents and sheep. Novel diagnostic strategies, which might include the use of surrogate markers of prion infection, along with prion removal strategies, might help to control the risk of iatrogenic prion spread through blood transfusions.

Key Points

  • Prion diseases are transmissible neurodegenerative conditions characterized by accumulation of a misfolded prion protein (PrPSc) in the brain

  • The prion diseases include Creutzfeldt–Jakob disease (CJD) in humans, bovine spongiform encephalopathy (BSE), and scrapie in sheep

  • Blood has not generally been regarded as a prion vector, but three individuals who contracted variant CJD through blood transfusion have recently been identified

  • Whole-blood fractionation experiments in animals revealed that the bulk of prion infectivity resides in leukocytes, plasma, cryoprecipitate, and Cohn fractions I–III

  • There is no effective screening method for identifying PrPSc in blood, so surrogate markers for prion diseases need to be identified in order that the quality of blood for transfusion can be controlled

  • The efficacy of filter systems for reducing prion titers in blood is currently being assessed

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Figure 1: Pathological deposition of prion protein within lymphoid follicles of an individual with variant Creutzfeldt–Jakob disease (vCJD).
Figure 2: Timeline of events underlying transmission of variant Creutzfeldt–Jakob disease (vCJD) prions via blood.
Figure 3: Incidence of variant Creutzfeldt–Jakob disease (vCJD) in Europe.

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Correspondence to Adriano Aguzzi.

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Aguzzi, A., Glatzel, M. Prion infections, blood and transfusions. Nat Rev Neurol 2, 321–329 (2006). https://doi.org/10.1038/ncpneuro0214

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