Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Prion infections, blood and transfusions

Nature Clinical Practice Neurology volume 2, pages 321–329 (2006)Cite this article

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

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

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.

Similar content being viewed by others

References

  1. Silveira JR et al. (2005) The most infectious prion protein particles. Nature 437: 257–261

    Article  CAS  Google Scholar 

  2. Aguzzi A and Miele G (2004) Recent advances in prion biology. Curr Opin Neurol 17: 337–342

    Article  CAS  Google Scholar 

  3. Brandner S et al. (1996) Normal host prion protein necessary for scrapie-induced neurotoxicity. Nature 379: 339–343

    Article  CAS  Google Scholar 

  4. Mead S et al. (2003) Balancing selection at the prion protein gene consistent with prehistoric kurulike epidemics. Science 300: 640–643

    Article  CAS  Google Scholar 

  5. Creutzfeldt HG (1920) Über eine eigenartige herdförmige Erkrankung des Zentralnervensystems. Z ges Neurol Psychiatr 57: 1–19

    Article  Google Scholar 

  6. Aguzzi A and Polymenidou M (2004) Mammalian prion biology: one century of evolving concepts. Cell 116: 313–327

    CAS  Google Scholar 

  7. Jakob A (1921) Über eigenartige Erkrankungen des Zentralnervensystems mit bemerkenswertem anatomischem Befunde. (Spastische Pseudosklerose-Encephalomyelopathie mit disseminierten Degenerationsherden). Z ges Neurol Psychiatr 64: 147–228

    Article  Google Scholar 

  8. Glatzel M et al. (2005) Human prion diseases: molecular and clinical aspects. Arch Neurol 62: 545–552

    Article  Google Scholar 

  9. Ghani AC et al. (2002) The transmission dynamics of BSE and vCJD. CR Biol 325: 37–47

    Article  Google Scholar 

  10. Hill AF et al. (1997) The same prion strain causes vCJD and BSE. Nature 389: 448–450

    Article  CAS  Google Scholar 

  11. Bruce ME et al. (1997) Transmissions to mice indicate that 'new variant' CJD is caused by the BSE agent. Nature 389: 498–501

    Article  CAS  Google Scholar 

  12. Aguzzi A and Weissmann C (1996) Spongiform encephalopathies: a suspicious signature. Nature 383: 666–667

    Article  CAS  Google Scholar 

  13. Aguzzi A (1996) Between cows and monkeys. Nature 381: 734

    Article  CAS  Google Scholar 

  14. Andrews NJ et al. (2003) Deaths from variant Creutzfeldt–Jakob disease in the UK. Lancet 361: 751–752

    Article  CAS  Google Scholar 

  15. The National Creutzfeldt–Jakob Disease Surveillance Unit [http://www.cjd.ed.ac.uk]

  16. Frigg R et al. (1999) Scrapie pathogenesis in subclinically infected B-cell-deficient mice. J Virol 73: 9584–9588

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Hilton DA et al. (2004) Prevalence of lymphoreticular prion protein accumulation in UK tissue samples. J Pathol 203: 733–739

    Article  CAS  Google Scholar 

  18. Peden AH et al. (2004) Preclinical vCJD after blood transfusion in a PRNP codon 129 heterozygous patient. Lancet 364: 527–529

    Article  Google Scholar 

  19. Collins S et al. (1999) Surgical treatment and risk of sporadic Creutzfeldt–Jakob disease: a case–control study. Lancet 353: 693–697

    Article  CAS  Google Scholar 

  20. Brown P et al. (1994) Human spongiform encephalopathy: the National Institutes of Health series of 300 cases of experimentally transmitted disease. Ann Neurol 35: 513–529

    Article  CAS  Google Scholar 

  21. Glatzel M et al. (2003) Extraneural pathologic prion protein in sporadic Creutzfeldt–Jakob disease. N Engl J Med 349: 1812–1820

    Article  CAS  Google Scholar 

  22. Ricketts MN et al. (1997) Is Creutzfeldt–Jakob disease transmitted in blood? Emerg Infect Dis 3: 155–163

    Article  CAS  Google Scholar 

  23. Bruce ME et al. (2001) Detection of variant Creutzfeldt–Jakob disease infectivity in extraneural tissues. Lancet 358: 208–209

    Article  CAS  Google Scholar 

  24. Hill AF et al. (1997) Diagnosis of new variant Creutzfeldt–Jakob disease by tonsil biopsy. Lancet 349: 99

    Article  CAS  Google Scholar 

  25. Llewelyn CA et al. (2004) Possible transmission of variant Creutzfeldt–Jakob disease by blood transfusion. Lancet 363: 417–421

    Article  CAS  Google Scholar 

  26. Health Protection Agency press statement: new case of variant CJD associated with blood transfusion [http://www.hpa.org.uk/hpa/news/articles/press_releases/2006/060209_cjd.htm]

  27. Weissmann C and Aguzzi A (1997) Bovine spongiform encephalopathy and early onset variant Creutzfeldt–Jakob disease. Curr Opin Neurobiol 7: 695–700

    Article  CAS  Google Scholar 

  28. Casalone C et al. (2004) Identification of a second bovine amyloidotic spongiform encephalopathy: molecular similarities with sporadic Creutzfeldt–Jakob disease. Proc Natl Acad Sci USA 101: 3065–3070

    Article  CAS  Google Scholar 

  29. Heikenwalder M et al. (2005) Chronic lymphocytic inflammation specifies the organ tropism of prions. Science 307: 1107–1110

    Article  CAS  Google Scholar 

  30. Wells GA et al. (2005) Pathogenesis of experimental bovine spongiform encephalopathy: preclinical infectivity in tonsil and observations on the distribution of lingual tonsil in slaughtered cattle. Vet Rec 156: 401–407

    Article  CAS  Google Scholar 

  31. Buschmann A and Groschup MH (2005) Highly bovine spongiform encephalopathy-sensitive transgenic mice confirm the essential restriction of infectivity to the nervous system in clinically diseased cattle. J Infect Dis 192: 934–942

    Article  Google Scholar 

  32. Ryder S et al. (2004) Demonstration of lateral transmission of scrapie between sheep kept under natural conditions using lymphoid tissue biopsy. Res Vet Sci 76: 211–217

    Article  CAS  Google Scholar 

  33. Seeger H et al. (2005) Coincident scrapie infection and nephritis lead to urinary prion excretion. Science 310: 324–326

    Article  CAS  Google Scholar 

  34. Houston F et al. (2000) Transmission of BSE by blood transfusion in sheep. Lancet 356: 999–1000

    Article  CAS  Google Scholar 

  35. Hunter N et al. (2002) Transmission of prion diseases by blood transfusion. J Gen Virol 83: 2897–2905

    Article  CAS  Google Scholar 

  36. Brown P et al. (1998) The distribution of infectivity in blood components and plasma derivatives in experimental models of transmissible spongiform encephalopathy. Transfusion 38: 810–816

    Article  CAS  Google Scholar 

  37. Holada K et al. (2002) Scrapie infectivity in hamster blood is not associated with platelets. J Virol 76: 4649–4650

    Article  CAS  Google Scholar 

  38. Gregori L et al. (2004) Partitioning of TSE infectivity during ethanol fractionation of human plasma. Biologicals 32: 1–10

    Article  CAS  Google Scholar 

  39. DebBurman SK et al. (1997) Chaperone-supervised conversion of prion protein to its protease-resistant form. Proc Natl Acad Sci USA 94: 13938–13943

    Article  CAS  Google Scholar 

  40. Fischer MB et al. (2000) Binding of disease-associated prion protein to plasminogen. Nature 408: 479–483

    Article  CAS  Google Scholar 

  41. Polymenidou M et al. (2005) Coexistence of multiple PrPSc types in individuals with Creutzfeldt–Jakob disease. Lancet Neurol 4: 805–814

    Article  CAS  Google Scholar 

  42. Bolton DC et al. (1991) Molecular location of a species-specific epitope on the hamster scrapie agent protein. J Virol 65: 3667–3675

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Korth C et al. (1997) Prion (PrPSc)-specific epitope defined by a monoclonal antibody. Nature 390: 74–77

    Article  CAS  Google Scholar 

  44. Saborio GP et al. (2001) Sensitive detection of pathological prion protein by cyclic amplification of protein misfolding. Nature 411: 810–813

    Article  CAS  Google Scholar 

  45. Castilla J et al. (2005) Detection of prions in blood. Nat Med 11: 982–985

    Article  CAS  Google Scholar 

  46. Miele G et al. (2001) A novel erythroid-specific marker of transmissible spongiform encephalopathies. Nat Med 7: 361–364

    Article  CAS  Google Scholar 

  47. Maury C (2001) Is EDRF a specific marker for TSEs? Nat Med 7: 641–642

    Article  CAS  Google Scholar 

  48. Wilson K and Ricketts MN (2004) Transfusion transmission of vCJD: a crisis avoided? Lancet 364: 477–479

    Article  Google Scholar 

  49. Sowemimo-Coker S et al. (2005) Removal of exogenous (spiked) and endogenous prion infectivity from red cells with a new prototype of leukoreduction filter. Transfusion 45: 1839–1844

    Article  CAS  Google Scholar 

  50. Schoch G et al. (2006) Analysis of prion strains by PrPSc profiling in sporadic Creutzfeldt–Jakob disease. PLoS Med 3: e14

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Chairman of the Department of Pathology at Zürich University, Switzerland

    Adriano Aguzzi

  2. heads the Institute of Neuropathology at the University of Hamburg, Germany

    Markus Glatzel

Authors
  1. Adriano Aguzzi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Markus Glatzel
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Adriano Aguzzi.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and permissions

About this article

Cite this article

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

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ncpneuro0214

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing