Evaluation of methods suitable for the sterilisation of surgical instruments contaminated with human prions.
Doctoral thesis, UCL (University College London).
Human prion disease is associated with the accumulation in brain of an abnormal glycoprotein known as prion protein. Prions are far more resistant to physical and chemical inactivation than conventional pathogens. In 1996 a new disease, variant Creutzfeldt-Jakob disease was recognised as distinct from sporadic Creutzfeldt-Jakob Disease and initially showed a rapid rise in incidence. The potential for iatrogenic transmission of prion disease via surgical instruments, despite presumed adequate sterilisation, is well documented. The long asymptomatic incubation periods seen in human prion diseases therefore provide a significant risk of transmission. This project investigated the disinfection of prion-contaminated surfaces, with the goal of developing a process applicable to medical instruments on a large scale. It also aimed to investigate the susceptibility of different brain regions to infection and the spread of peripheral infection to brain, as well as the mechanisms of disease transmission from infected surfaces to tissues. Potential sterilisation procedures were tested on steel wires that had been incubated in infectious brain homogenate. These wires were then inserted into the brains of appropriate indicator mice, which were observed for the clinical signs of prion disease and subsequently investigated using immunohistochemistry. To investigate the susceptibility of different brain regions to infection, steel and plastic spheres were inserted stereotaxically and mice culled at different time points and subjected to immunohistochemical examination. Intraperitoneal and subcutaneous insertion of these spheres was used to investigate the travel of infectivity from peripheral tissues to the central nervous system. Attempts were made to develop a high sensitivity cell culture assay, to enable quantification of the amount of sterilisation produced by different methods, and to investigate their kinetics.
|Title:||Evaluation of methods suitable for the sterilisation of surgical instruments contaminated with human prions|
|Additional information:||Authorisation for digitisation not received|
|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Neurology > Neurodegenerative Diseases|
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