No abstract

Chronic wasting disease (CWD) of deer and elk is endemic in a tri-corner area of Colorado, Wyoming, and Nebraska, and new foci of CWD have been detected in other parts of the United States. Although detection in some areas may be related to increased surveillance, introduction of CWD due to translocation or natural migration of animals may account for some new foci of infection. Increasing spread of CWD has raised concerns about the potential for increasing human exposure to the CWD agent. The foodborne transmission of bovine spongiform encephalopathy to humans indicates that the species barrier may not completely protect humans from animal prion diseases. Conversion of human prion protein by CWD-associated prions has been demonstrated in an in vitro cell-free experiment, but limited investigations have not identified strong evidence for CWD transmission to humans. More epidemiologic and laboratory studies are needed to monitor the possibility of such transmissions.

Objective:We present the National Prion Disease Pathology Surveillance Center’s (NPDPSC) experience using cerebrospinal fluid (CSF) real time quaking induced conversion (RT-QuIC) as a diagnostic test, examine factors associated with false negative RT-QuIC results, and investigate RT-QuIC’s impact on prion disease surveillance.Methods:Between May 2015-April 2018, the NPDPSC received 10,498 CSF specimens that were included in the study. Sensitivity and specificity analyses were performed using 567 autopsy verified cases. Prion disease type, demographic characteristics, specimen color, and time variables were examined for association with RT-QuIC results. The effect of including positive RT-QuIC cases in prion disease surveillance was examined.Results:The diagnostic sensitivity and specificity of RT-QuIC across all prion diseases was 90.3% and 98.5%, respectively. Diagnostic sensitivity was lower for fatal familial insomnia, Gerstmann-Sträussler-Scheinker disease, sporadic fatal insomnia, variably protease sensitive prionopathy, and the VV1 and MM2 subtypes of sCJD. Individuals with prion disease and negative RT-QuIC results were younger, had elevated tau levels, and non-elevated 14-3-3 levels compared to RT-QuIC positive cases. Sensitivity was high throughout the disease course. Some cases that initially tested RT-QuIC negative had a subsequent specimen test positive. Including positive RT-QuIC cases in surveillance statistics increased laboratory-based case ascertainment of prion disease by 90% over autopsy alone.Conclusions:RT-QuIC has high sensitivity and specificity for diagnosing prion diseases. Sensitivity limitations are associated with prion disease type, age, and related CSF diagnostic results. RT-QuIC greatly improves laboratory-based prion disease ascertainment for surveillance purposes.Classification of Evidence:This study provides Class III evidence that 2nd generation real time quaking-induced conversion (RT-QuIC) identifies prion disease with sensitivity of 90.3% and specificity of 98.5%, among patients being screened for these diseases due to concerning symptoms.