Prion Epidemiology And The Npdpsc’s Experience With Rt-Quic
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Abstract
Prion diseases, or transmissible spongiform encephalopathies, constitute a wide array of invariably fatal rapidly progressive neurodegenerative illnesses that affect both humans and animals. The gold standard of diagnosis for these diseases is through neuropathologic examination of brain tissue following autopsy. In September 2018, the Centers for Disease Control and Prevention (CDC) added positive real-time quaking-induced conversion (RT-QuIC) test result as a likely indicator of certain human prion diseases. With high sensitivity and specificity approaching 100%, RT-QuIC has quickly become one of the most powerful antemortem diagnostic tools.
This paper will demonstrate why changes in diagnostic criteria and reporting metrics are appropriate and innovative in the diagnosis and surveillance of prion disease. An introduction to prion biology and epidemiology in the 21st century is followed by the presentation of the National Prion Disease Pathology Surveillance Center’s (NPDPSC) experience with 2nd generation RT-QuIC over a 3-year period. In this observational study, 10,498 unique cerebrospinal fluid (CSF) samples taken from suspected cases of prion disease were sent to the NPDPSC. 567 of these cases also went on to autopsy; autopsy results were then used to determine RT-QuIC’s sensitivity (90.3%) and specificity (99.8%).
Type of prion disease, illness duration, and various demographic characteristics were analyzed to determine possible influences on RT-QuIC results. Sensitivity was found to be lower among rarer prion diseases, such as genetic and atypical sporadic diseases. Poor sample quality was also associated with lower sensitivity. Sporadic Creutzfeldt-Jakob Disease (sCJD) cases were more likely to produce false negative RT-QuIC results if samples were from younger individuals or from cases with longer disease durations.
In conclusion, RT-QuIC is a highly sensitive and specific test that can be an aid in ascertaining an extremely rare disease. However, this study has shown that its sensitivity and specificity can be affected by disease type, specimen quality, and demographic characteristics among individuals with suspected cases of prion disease. Moving forward, this novel assay will become an invaluable objective tool in diagnosing prion disease antemortem.