Publications (2)9.67 Total impact
Chapter: Disinfection of Prions[Show abstract] [Hide abstract]
ABSTRACT: Prions are unprecedented transmissible pathogenic agents that cause a group of fatal neurodegenerative diseases, including Creutzfeldt-Jakob disease (CJD) and kuru in humans, bovine spongiform encephalopathy (BSE) in cattle, chronic wasting disease (CWD) in deer and elk, and scrapie in sheep and goats. Prions are resistant to standard disinfection and sterilization procedures validated against viruses and bacteria. There are well documented cases of iatrogenic prion transmission from surgical instruments and cadaveric tissue. The lack of noncorrosive procedures that inactivate prions is a cause for concern for hospital infection-control departments. A novel method to inactivate human prions completely, using sodium dodecyl sulfate at acidic pH (acidic SDS), is reported here. Prion inactivation was demonstrated on both brain homogenate and on the surface of contaminated surgical stainless steel, the latter of which proved significantly more resistant to inactivation.
Article: Diagnosis of human prion disease[Show abstract] [Hide abstract]
ABSTRACT: With the discovery of the prion protein (PrP), immunodiagnostic procedures were applied to diagnose Creutzfeldt-Jakob disease (CJD). Before development of the conformation-dependent immunoassay (CDI), all immunoassays for the disease-causing PrP isoform (PrPSc) used limited proteolysis to digest the precursor cellular PrP (PrPC). Because the CDI is the only immunoassay that measures both the protease-resistant and protease-sensitive forms of PrPSc, we used the CDI to diagnose human prion disease. The CDI gave a positive signal for PrPSc in all 10-24 brain regions (100%) examined from 28 CJD patients. A subset of 18 brain regions from 8 patients with sporadic CJD (sCJD) was examined by histology, immunohistochemistry (IHC), and the CDI. Three of the 18 regions (17%) were consistently positive by histology and 4 of 18 (22%) by IHC for the 8 sCJD patients. In contrast, the CDI was positive in all 18 regions (100%) for all 8 sCJD patients. In both gray and white matter, approximately 90% of the total PrPSc was protease-sensitive and, thus, would have been degraded by procedures using proteases to eliminate PrPC. Our findings argue that the CDI should be used to establish or rule out the diagnosis of prion disease when a small number of samples is available as is the case with brain biopsy. Moreover, IHC should not be used as the standard against which all other immunodiagnostic techniques are compared because an immunoassay, such as the CDI, is substantially more sensitive.