Decontamination of prions, prion-associated amyloid and inefectivity from surgical stainless steel - implications for the risk of iatrogenic transmission of CJD

Abstract

The physicochemical nature of the infectious agent in prion diseases creates a
significant challenge for decontamination services. It has been shown to be both resistant to
standard methods of decontamination, used to inactivate viruses and bacteria, and to associate
avidly with surgical stainless steel. Moreover, the pathophysiology of the variant, iatrogenic
and sporadic forms of Creutzfeldt-Jakob Disease (CJD) suggests deposition of the infectious
agent across a wide range of extraneural, lymphoid tissues, as well as in the skeletal muscle
and blood. Coupled with the potential for asymptomatic carriers, there is a significant risk of
iatrogenic transmission of CJD through both neurosurgical procedures and standard surgery.

This PhD study was undertaken in order to improve methods of instrument
decontamination and to evaluate prion detection techniques and their applicability for the
assessment of prion inactivation and removal. The project has provided relevant, critical
assessment of hospital decontamination procedures, in addition to guidance on how working
protocols should be improved to provide a cleaner and safer end product for the patient.
Moreover, laboratory studies have been performed to evaluate current methods of prion
decontamination in the context of hospital procedures for instrument reprocessing. Challenges
faced by sterile service departments, such as soil drying and surface degradation, have been
addressed and their impact on the risk of iatrogenic transmission of prions has been
investigated. Critically, the use of a fluorescent amyloid fluorophore for the detection of prionassociated
amyloid as a marker for disease permitted the investigation of the role of amyloid
in infectious disease under denaturing conditions. Correlation of this detection technique with
the identification of PrPres by Western blot and infectious disease suggested that, whilst
fluorescent detection of prion-associated amyloid was more sensitive than Western blot, PrPres
detection was more specific relative to infectivity. Improved fluorophores, with greater
sensitivity, have been evaluated which will enhance in situ detection of prions in the future.

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Identifiers

ORCID for C.W. Keevil: orcid.org/0000-0003-1917-7706

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