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.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:509561 |
| Date | January 2009 |
| Creators | Howlin, Robert |
| Contributors | Keevil, Charles |
| Publisher | University of Southampton |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | https://eprints.soton.ac.uk/150533/ |
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