Advancing Surgical Instrument Safety: A Screen of Oxidative and Alkaline Prion Decontaminants Using Real-time Quaking-induced Conversion with Prion-coated Steel Beads As Surgical Instrument Mimetic

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2024 Jun 13

PMID 38870196

Authors

Daniel Heinzer

Merve Avar

Manuela Pfammatter

Rita Moos

Petra Schwarz

Matthias T Buhmann

Benjamin Kuhn

Stefan Mauerhofer

Urs Rosenberg

Adriano Aguzzi

Simone Hornemann

Affiliations

Soon will be listed here.

Abstract

Iatrogenic transmission of prions, the infectious agents of fatal Creutzfeldt-Jakob disease, through inefficiently decontaminated medical instruments remains a critical issue. Harsh chemical treatments are effective, but not suited for routine reprocessing of reusable surgical instruments in medical cleaning and disinfection processes due to material incompatibilities. The identification of mild detergents with activity against prions is therefore of high interest but laborious due to the low throughput of traditional assays measuring prion infectivity. Here, we report the establishment of TESSA (sTainlESs steel-bead Seed Amplification assay), a modified real-time quaking induced cyclic amplification (RT-QuIC) assay that explores the propagation activity of prions with stainless steel beads. TESSA was applied for the screening of about 70 different commercially available and novel formulations and conditions for their prion inactivation efficacy. One hypochlorite-based formulation, two commercially available alkaline formulations and a manual alkaline pre-cleaner were found to be highly effective in inactivating prions under conditions simulating automated washer-disinfector cleaning processes. The efficacy of these formulations was confirmed in vivo in a murine prion infectivity bioassay, yielding a reduction of the prion titer for bead surface adsorbed prions below detectability. Our data suggest that TESSA represents an effective method for a rapid screening of prion-inactivating detergents, and that alkaline and oxidative formulations are promising in reducing the risk of potential iatrogenic prion transmission through insufficiently decontaminated instrument surfaces.

Citing Articles

Sodium hypochlorite inactivation of human CJD prions.

Groveman B, Race B, Hughson A, Haigh C PLoS One. 2024; 19(11):e0312837.

PMID: 39509453 PMC: 11542847. DOI: 10.1371/journal.pone.0312837.

References

Thomas J, Chenoweth C, Sullivan S . Iatrogenic Creutzfeldt-Jakob disease via surgical instruments. J Clin Neurosci. 2013; 20(9):1207-12. DOI: 10.1016/j.jocn.2013.01.007. View

Nakano Y, Akamatsu N, Mori T, Sano K, Satoh K, Nagayasu T . Sequential Washing with Electrolyzed Alkaline and Acidic Water Effectively Removes Pathogens from Metal Surfaces. PLoS One. 2016; 11(5):e0156058. PMC: 4880284. DOI: 10.1371/journal.pone.0156058. View

Berberidou C, Xanthopoulos K, Paspaltsis I, Lourbopoulos A, Polyzoidou E, Sklaviadis T . Homogenous photocatalytic decontamination of prion infected stainless steel and titanium surfaces. Prion. 2013; 7(6):488-95. PMC: 4201617. DOI: 10.4161/pri.27180. View

Flechsig E, Hegyi I, Enari M, Schwarz P, Collinge J, Weissmann C . Transmission of scrapie by steel-surface-bound prions. Mol Med. 2001; 7(10):679-84. PMC: 1949999. View

Aguzzi A, Heikenwalder M, Polymenidou M . Insights into prion strains and neurotoxicity. Nat Rev Mol Cell Biol. 2007; 8(7):552-61. DOI: 10.1038/nrm2204. View

Prusiner S, Cochran S, Groth D, Downey D, Bowman K, Martinez H . Measurement of the scrapie agent using an incubation time interval assay. Ann Neurol. 1982; 11(4):353-8. DOI: 10.1002/ana.410110406. View

Hirata Y, Ito H, Furuta T, Ikuta K, Sakudo A . Degradation and destabilization of abnormal prion protein using alkaline detergents and proteases. Int J Mol Med. 2010; 25(2):267-70. View

Erana H, Perez-Castro M, Garcia-Martinez S, Charco J, Lopez-Moreno R, Diaz-Dominguez C . A Novel, Reliable and Highly Versatile Method to Evaluate Different Prion Decontamination Procedures. Front Bioeng Biotechnol. 2020; 8:589182. PMC: 7658626. DOI: 10.3389/fbioe.2020.589182. View

Vascellari S, Orru C, Hughson A, King D, Barron R, Wilham J . Prion seeding activities of mouse scrapie strains with divergent PrPSc protease sensitivities and amyloid plaque content using RT-QuIC and eQuIC. PLoS One. 2012; 7(11):e48969. PMC: 3489776. DOI: 10.1371/journal.pone.0048969. View

10.

Falsig J, Julius C, Margalith I, Schwarz P, Heppner F, Aguzzi A . A versatile prion replication assay in organotypic brain slices. Nat Neurosci. 2007; 11(1):109-17. PMC: 2754795. DOI: 10.1038/nn2028. View

11.

Adjou K, Demaimay R, Lasmezas C, Seman M, Deslys J, Dormont D . Differential effects of a new amphotericin B derivative, MS-8209, on mouse BSE and scrapie: implications for the mechanism of action of polyene antibiotics. Res Virol. 1996; 147(4):213-8. DOI: 10.1016/0923-2516(96)89651-8. View

12.

Williams K, Hughson A, Chesebro B, Race B . Inactivation of chronic wasting disease prions using sodium hypochlorite. PLoS One. 2019; 14(10):e0223659. PMC: 6777796. DOI: 10.1371/journal.pone.0223659. View

13.

Bonda D, Manjila S, Mehndiratta P, Khan F, Miller B, Onwuzulike K . Human prion diseases: surgical lessons learned from iatrogenic prion transmission. Neurosurg Focus. 2016; 41(1):E10. PMC: 5082740. DOI: 10.3171/2016.5.FOCUS15126. View

14.

Head M, Ironside J . vCJD and the gut: implications for endoscopy. Gut. 2006; 56(1):9-11. PMC: 1856665. DOI: 10.1136/gut.2006.101964. View

15.

Avar M, Heinzer D, Thackray A, Liu Y, Hruska-Plochan M, Sellitto S . An arrayed genome-wide perturbation screen identifies the ribonucleoprotein Hnrnpk as rate-limiting for prion propagation. EMBO J. 2022; 41(23):e112338. PMC: 9713719. DOI: 10.15252/embj.2022112338. View

16.

Lehmann S, Pastore M, Rogez-Kreuz C, Richard M, Belondrade M, Rauwel G . New hospital disinfection processes for both conventional and prion infectious agents compatible with thermosensitive medical equipment. J Hosp Infect. 2009; 72(4):342-50. DOI: 10.1016/j.jhin.2009.03.024. View

17.

Luhr K, Low P, Taraboulos A, Bergman T, Kristensson K . Prion adsorption to stainless steel is promoted by nickel and molybdenum. J Gen Virol. 2009; 90(Pt 11):2821-2828. DOI: 10.1099/vir.0.012302-0. View

18.

Alper T, Cramp W, HAIG D, Clarke M . Does the agent of scrapie replicate without nucleic acid?. Nature. 1967; 214(5090):764-6. DOI: 10.1038/214764a0. View

19.

McKinley M, MEYER R, Kenaga L, Rahbar F, Cotter R, Serban A . Scrapie prion rod formation in vitro requires both detergent extraction and limited proteolysis. J Virol. 1991; 65(3):1340-51. PMC: 239910. DOI: 10.1128/JVI.65.3.1340-1351.1991. View

20.

Peretz D, Supattapone S, Giles K, Vergara J, Freyman Y, Lessard P . Inactivation of prions by acidic sodium dodecyl sulfate. J Virol. 2005; 80(1):322-31. PMC: 1317507. DOI: 10.1128/JVI.80.1.322-331.2006. View