Prions are comprised principally of aggregates of a misfolded host protein and cause fatal transmissible neurodegenerative disorders of mammals, such as variant Creutzfeldt–Jakob disease in humans and bovine spongiform encephalopathy in cattle. Prions pose significant public health concerns through contamination of blood products and surgical instruments, and can resist conventional hospital sterilization methods. Prion infectivity binds avidly to surgical steel and can efficiently transfer infectivity to a suitable host, and much research has been performed to achieve effective prion decontamination of metal surfaces. Here, we exploit the highly sensitive Standard Steel-Binding Assay (SSBA) to perform a direct comparison of a variety of commercially available decontamination reagents marketed for the removal of prions, alongside conventional sterilization methods. We demonstrate that the efficacy of marketed prion decontamination reagents is highly variable and that the SSBA is able to rapidly evaluate current and future decontamination reagents.


Article metrics loading...

Loading full text...

Full text loading...



  1. Asante, E. A., Linehan, J. M., Desbruslais, M., Joiner, S., Gowland, I., Wood, A. L., Welch, J., Hill, A. F., Lloyd, S. E. & other authors(2002). BSE prions propagate as either variant CJD-like or sporadic CJD-like prion strains in transgenic mice expressing human prion protein. EMBO J 21, 6358–6366.[CrossRef] [Google Scholar]
  2. Asante, E. A., Gowland, I., Grimshaw, A., Linehan, J. M., Smidak, M., Houghton, R., Osiguwa, O., Tomlinson, A., Joiner, S. & other authors(2009). Absence of spontaneous disease and comparative prion susceptibility of transgenic mice expressing mutant human prion proteins. J Gen Virol 90, 546–558.[CrossRef] [Google Scholar]
  3. Bernoulli, C., Siegfried, J., Baumgartner, G., Regli, F., Rabinowicz, T., Gajdusek, D. C. & Gibbs, C. J., Jr(1977). Danger of accidental person-to-person transmission of Creutzfeldt-Jakob disease by surgery. . Lancet 1, 478–479. [Google Scholar]
  4. Bramble, M. G. & Ironside, J. W.(2002). Creutzfeldt-Jakob disease: implications for gastroenterology. Gut 50, 888–890.[CrossRef] [Google Scholar]
  5. Bruce, M. E., McConnell, I., Will, R. G. & Ironside, J. W.(2001). Detection of variant Creutzfeldt–Jakob disease infectivity in extraneural tissues. Lancet 358, 208–209.[CrossRef] [Google Scholar]
  6. Bueler, H., Aguzzi, A., Sailer, A., Greiner, R. A., Autenried, P., Aguet, M. & Weissmann, C.(1993). Mice devoid of PrP are resistant to scrapie. Cell 73, 1339–1347.[CrossRef] [Google Scholar]
  7. Clewley, J. P., Kelly, C. M., Andrews, N., Vogliqi, K., Mallinson, G., Kaisar, M., Hilton, D. A., Ironside, J. W., Edwards, P. & other authors(2009). Prevalence of disease related prion protein in anonymous tonsil specimens in Britain: cross sectional opportunistic survey. BMJ 338, b1442.[CrossRef] [Google Scholar]
  8. Collinge, J.(2001). Prion diseases of humans and animals: their causes and molecular basis. Annu Rev Neurosci 24, 519–550.[CrossRef] [Google Scholar]
  9. Collinge, J. & Clarke, A. R.(2007). A general model of prion strains and their pathogenicity. Science 318, 930–936.[CrossRef] [Google Scholar]
  10. Collins, S., Law, M. G., Fletcher, A., Boyd, A., Kaldor, J. & Masters, C. L.(1999). Surgical treatment and risk of sporadic Creutzfeldt–Jakob disease: a case-control study. Lancet 353, 693–697.[CrossRef] [Google Scholar]
  11. Cronier, S., Gros, N., Tattum, M. H., Jackson, G. S., Clarke, A. R., Collinge, J. & Wadsworth, J. D.(2008). Detection and characterization of proteinase K-sensitive disease-related prion protein with thermolysin. Biochem J 416, 297–305.[CrossRef] [Google Scholar]
  12. Davanipour, Z., Alter, M., Sobel, E. & Callahan, M.(1985). Sheep consumption: a possible source of spongiform encephalopathy in humans. Neuroepidemiology 4, 240–249.[CrossRef] [Google Scholar]
  13. de Pedro-Cuesta, J., Mahillo-Fernandez, I., Rabano, A., Calero, M., Cruz, M., Siden, A., Laursen, H., Falkenhorst, G. & Molbak, K.(2010). Nosocomial transmission of sporadic Creutzfeldt-Jakob disease: results from a risk-based assessment of surgical interventions. J Neurol Neurosurg Psychiatry (14 June; Epub ahead of print). [Google Scholar]
  14. Edgeworth, J. A., Jackson, G. S., Clarke, A. R., Weissmann, C. & Collinge, J.(2009). Highly sensitive, quantitative cell-based assay for prions adsorbed to solid surfaces. Proc Natl Acad Sci U S A 106, 3479–3483.[CrossRef] [Google Scholar]
  15. Fichet, G., Comoy, E., Duval, C., Antloga, K., Dehen, C., Charbonnier, A., McDonnell, G., Brown, P., Lasmezas, C. I. & Deslys, J. P.(2004). Novel methods for disinfection of prion-contaminated medical devices. Lancet 364, 521–526.[CrossRef] [Google Scholar]
  16. Fischer, M., Rulicke, T., Raeber, A., Sailer, A., Moser, M., Oesch, B., Brandner, S., Aguzzi, A. & Weissmann, C.(1996). Prion protein (PrP) with amino-proximal deletions restoring susceptibility of PrP knockout mice to scrapie. EMBO J 15, 1255–1264. [Google Scholar]
  17. Flechsig, E., Hegyi, I., Enari, M., Schwarz, P., Collinge, J. & Weissmann, C.(2001). Transmission of scrapie by steel-surface-bound prions. Mol Med 7, 679–684. [Google Scholar]
  18. Frosh, A., Smith, L. C., Jackson, C. J., Linehan, J., Brandner, S., Wadsworth, J. D. & Collinge, J.(2004). Analysis of 2000 consecutive UK tonsillectomy specimens for disease-related prion protein. Lancet 364, 1260–1262.[CrossRef] [Google Scholar]
  19. Gibbs, C. J., Jr, Asher, D. M., Kobrine, A., Amyx, H. L., Sulima, M. P. & Gajdusek, D. C.(1994). Transmission of Creutzfeldt–Jakob disease to a chimpanzee by electrodes contaminated during neurosurgery. J Neurol Neurosurg Psychiatry 57, 757–758.[CrossRef] [Google Scholar]
  20. Giles, K., Glidden, D. V., Beckwith, R., Seoanes, R., Peretz, D., DeArmond, S. J. & Prusiner, S. B.(2008). Resistance of bovine spongiform encephalopathy (BSE) prions to inactivation. PLoS Pathog 4, e1000206.[CrossRef] [Google Scholar]
  21. Glatzel, M., Abela, E., Maissen, M. & Aguzzi, A.(2003). Extraneural pathologic prion protein in sporadic Creutzfeldt–Jakob disease. N Engl J Med 349, 1812–1820.[CrossRef] [Google Scholar]
  22. Griffith, J. S.(1967). Self replication and scrapie. Nature 215, 1043–1044.[CrossRef] [Google Scholar]
  23. Head, M. W., Ritchie, D., Smith, N., McLoughlin, V., Nailon, W., Samad, S., Masson, S., Bishop, M., McCardle, L. & Ironside, J. W.(2004). Peripheral tissue involvement in sporadic, iatrogenic, and variant Creutzfeldt–Jakob disease: an immunohistochemical, quantitative, and biochemical study. Am J Pathol 164, 143–153.[CrossRef] [Google Scholar]
  24. Hernandez-Palazon, J., Martinez-Lage, J. F., Tortosa, J. A. & Garcia-Cayuela, J. M.(1998). Anaesthetic management in patients suspected of, or at risk of, having Creutzfeldt–Jakob disease. Br J Anaesth 80, 516–518.[CrossRef] [Google Scholar]
  25. Hill, A. F., Desbruslais, M., Joiner, S., Sidle, K. C., Gowland, I., Collinge, J., Doey, L. J. & Lantos, P.(1997). The same prion strain causes vCJD and BSE. Nature 389, 448–450, 526.[CrossRef] [Google Scholar]
  26. Hill, A. F., Butterworth, R. J., Joiner, S., Jackson, G. S., Rossor, M. N., Thomas, D. J., Frosh, A., Tolley, N., Bell, J. E. & other authors(1999). Investigation of variant Creutzfeldt–Jakob disease and other human prion diseases with tonsil biopsy samples. Lancet 353, 183–189.[CrossRef] [Google Scholar]
  27. Hilton, D. A., Ghani, A. C., Conyers, L., Edwards, P., McCardle, L., Ritchie, D., Penney, M., Hegazy, D. & Ironside, J. W.(2004). Prevalence of lymphoreticular prion protein accumulation in UK tissue samples. J Pathol 203, 733–739.[CrossRef] [Google Scholar]
  28. HPA Press Office(2009). vCJD abnormal prion protein found in a patient with haemophilia at post mortem.
  29. Jackson, G. S., McKintosh, E., Flechsig, E., Prodromidou, K., Hirsch, P., Linehan, J., Brandner, S., Clarke, A. R., Weissmann, C. & Collinge, J.(2005). An enzyme-detergent method for effective prion decontamination of surgical steel. J Gen Virol 86, 869–878.[CrossRef] [Google Scholar]
  30. Joiner, S., Linehan, J., Brandner, S., Wadsworth, J. D. & Collinge, J.(2002). Irregular presence of abnormal prion protein in appendix in variant Creutzfeldt–Jakob disease. J Neurol Neurosurg Psychiatry 73, 597–598.[CrossRef] [Google Scholar]
  31. Joiner, S., Linehan, J., Brandner, S., Wadsworth, J. D. & Collinge, J.(2005). High Levels of disease related prion protein in the ileum in variant Creutzfeldt–Jakob disease. Gut 54, 1506–1508. [Google Scholar]
  32. Klohn, P. C., Stoltze, L., Flechsig, E., Enari, M. & Weissmann, C.(2003). A quantitative, highly sensitive cell-based infectivity assay for mouse scrapie prions. Proc Natl Acad Sci U S A 100, 11666–11671.[CrossRef] [Google Scholar]
  33. Lemmer, K., Mielke, M., Kratzel, C., Joncic, M., Oezel, M., Pauli, G. & Beekes, M.(2008). Decontamination of surgical instruments from prions. II. In vivo findings with a model system for testing the removal of scrapie infectivity from steel surfaces. J Gen Virol 89, 348–358.[CrossRef] [Google Scholar]
  34. Llewelyn, C. A., Hewitt, P. E., Knight, R. S., Amar, K., Cousens, S., Mackenzie, J. & Will, R. G.(2004). Possible transmission of variant Creutzfeldt–Jakob disease by blood transfusion. Lancet 363, 417–421.[CrossRef] [Google Scholar]
  35. Mahillo-Fernandez, I., Pedro-Cuesta, J., Bleda, M. J., Cruz, M., Molbak, K., Laursen, H., Falkenhorst, G., Martinez-Martin, P. & Siden, A.(2008). Surgery and risk of sporadic Creutzfeldt–Jakob disease in Denmark and Sweden: registry-based case-control studies. Neuroepidemiology 31, 229–240.[CrossRef] [Google Scholar]
  36. Minatogawa, T. & Kumoi, T.(1999). Problems in utility and safety of otological allografts. Transplant Proc 31, 2036–2037.[CrossRef] [Google Scholar]
  37. Murdoch, H., Taylor, D., Dickinson, J., Walker, J. T., Perrett, D., Raven, N. D. & Sutton, J. M.(2006). Surface decontamination of surgical instruments: an ongoing dilemma. J Hosp Infect 63, 432–438.[CrossRef] [Google Scholar]
  38. Notari, S., Moleres, F. J., Hunter, S. B., Belay, E. D., Schonberger, L. B., Cali, I., Parchi, P., Shieh, W. J., Brown, P. & other authors(2010). Multiorgan detection and characterization of protease-resistant prion protein in a case of variant CJD examined in the United States. PLoS ONE 5, e8765.[CrossRef] [Google Scholar]
  39. Peden, A. H., Head, M. W., Ritchie, D. L., Bell, J. E. & Ironside, J. W.(2004). Preclinical vCJD after blood transfusion in a PRNP codon 129 heterozygous patient. Lancet 364, 527–529.[CrossRef] [Google Scholar]
  40. Peden, A., McCardle, L., Head, M. W., Love, S., Ward, H. J., Cousens, S. N., Keeling, D. M., Millar, C. M., Hill, F. G. & Ironside, J. W.(2010). Variant CJD infection in the spleen of a neurologically asymptomatic UK adult patient with haemophilia. Haemophilia 16, 296–304.[CrossRef] [Google Scholar]
  41. Peretz, D., Supattapone, S., Giles, K., Vergara, J., Freyman, Y., Lessard, P., Safar, J. G., Glidden, D. V., McCulloch, C. & other authors(2006). Inactivation of prions by acidic sodium dodecyl sulfate. J Virol 80, 322–331.[CrossRef] [Google Scholar]
  42. Prusiner, S. B.(1982). Novel proteinaceous infectious particles cause scrapie. Science 216, 136–144.[CrossRef] [Google Scholar]
  43. Prusiner, S. B., Groth, D. F., McKinley, M. P., Cochran, S. P., Bowman, K. & Kasper, K. C.(1981). Thiocyanate and hydroxyl ions inactivate the scrapie agent. Proc Natl Acad Sci U S A 78, 4606–4610.[CrossRef] [Google Scholar]
  44. Rutala, W. A. & Weber, D. J.(2001). Creutzfeldt–Jakob disease: recommendations for disinfection and sterilization. Clin Infect Dis 32, 1348–1356.[CrossRef] [Google Scholar]
  45. SEAC(2006). Position statement on methods to evaluate decontamination technologies for surgical instruments. http://www.seac.gov.uk/statements/statement310806.htm.
  46. Smith, A., Dickson, M., Aitken, J. & Bagg, J.(2002). Contaminated dental instruments. J Hosp Infect 51, 233–235.[CrossRef] [Google Scholar]
  47. Somerville, R. A., Oberthur, R. C., Havekost, U., MacDonald, F., Taylor, D. M. & Dickinson, A. G.(2002). Characterization of thermodynamic diversity between transmissible spongiform encephalopathy agent strains and its theoretical implications. J Biol Chem 277, 11084–11089.[CrossRef] [Google Scholar]
  48. Taylor, D. M.(1991). Inactivation of the unconventional agents of scrapie, bovine spongiform encephalopathy and Creutzfeldt–Jakob disease. J Hosp Infect 18, 141–146 (Suppl. A).[CrossRef] [Google Scholar]
  49. Taylor, D. M., Fernie, K., McConnell, I. & Steele, P. J.(1998). Observations on thermostable subpopulations of the unconventional agents that cause transmissible degenerative encephalopathies. Vet Microbiol 64, 33–38.[CrossRef] [Google Scholar]
  50. Taylor, D. M., Fernie, K., McConnell, I. & Steele, P. J.(1999). Survival of scrapie agent after exposure to sodium dodecyl sulphate and heat. Vet Microbiol 67, 13–16.[CrossRef] [Google Scholar]
  51. Wadsworth, J. D., Joiner, S., Hill, A. F., Campbell, T. A., Desbruslais, M., Luthert, P. J. & Collinge, J.(2001). Tissue distribution of protease resistant prion protein in variant CJD using a highly sensitive immuno-blotting assay. Lancet 358, 171–180.[CrossRef] [Google Scholar]
  52. Wadsworth, J. D., Joiner, S., Fox, K., Linehan, J., Desbruslais, M., Brandner, S., Asante, E. A. & Collinge, J.(2007). Prion infectivity in variant Creutzfeldt–Jakob disease rectum. Gut 56, 90–94.[CrossRef] [Google Scholar]
  53. Walker, J. T., Dickinson, J., Sutton, J. M., Raven, N. D. & Marsh, P. D.(2007). Cleanability of dental instruments – implications of residual protein and risks from Creutzfeldt–Jakob disease. Br Dent J 203, 395–401.[CrossRef] [Google Scholar]
  54. Ward, H. J., Everington, D., Croes, E. A., Alperovitch, A., Delasnerie-Laupretre, N., Zerr, I., Poser, S. & van Duijn, C. M.(2002). Sporadic Creutzfeldt–Jakob disease and surgery: a case-control study using community controls. Neurology 59, 543–548.[CrossRef] [Google Scholar]
  55. WHO(1999).WHO Infection Control Guidelines for Transmissible Spongiform Encephalopathies. Geneva. : WHO. [Google Scholar]
  56. Wroe, S. J., Pal, S., Siddique, D., Hyare, H., Macfarlane, R., Joiner, S., Linehan, J., Brandner, S., Wadsworth, J. D. & other authors(2006). Clinical presentation and pre-mortem diagnosis of variant Creutzfeldt–Jakob disease associated with blood transfusion: a case report. Lancet 368, 2061–2067.[CrossRef] [Google Scholar]
  57. Yan, Z. X., Stitz, L., Heeg, P., Pfaff, E. & Roth, K.(2004). Infectivity of prion protein bound to stainless steel wires: a model for testing decontamination procedures for transmissible spongiform encephalopathies. Infect Control Hosp Epidemiol 25, 280–283.[CrossRef] [Google Scholar]
  58. Zobeley, E., Flechsig, E., Cozzio, A., Masato, E. & Weissmann, C.(1999). Infectivity of scrapie prions bound to a stainless steel surface. Mol Med 5, 240–243. [Google Scholar]

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error