Sensitivity of protein misfolding cyclic amplification versus immunohistochemistry in ante-mortem detection of chronic wasting disease

• DOI: 10.1099/vir.0.039073-0
• Publication Date: 2012-01-26T06:15:01Z
• Authors: Nicholas J. Haley; Candace K. Mathiason; Scott Carver; Glenn C. Telling; Mark D. Zabel; Edward A. Hoover
• Keywords: Chronic wasting disease; Tonsil; Pathogenesis; Wasting Syndrome; PRNP; Gold standard (test)

As the only prion disease affecting free-ranging animals, ante-mortem identification of affected cervids has become paramount in understanding chronic wasting (CWD) pathogenesis, prevalence and control horizontal or vertical transmission. To seek maximal sensitivity detection CWD infection, this study used paired tonsil biopsy samples collected at various time points from 48 CWD-exposed to compare blinded serial protein misfolding cyclic amplification (sPMCA) with assay long considered 'gold standard' for detection, immunohistochemistry (IHC). sPMCA-negative controls (34 % evaluated) included tissues mock-inoculated animals unspiked negative controls, all which tested throughout course study. It was found that sPMCA on biopsies detected infection significantly earlier (2.78 months, 95 confidence interval 2.40-3.15) than conventional IHC. Interestingly, a correlation observed between early by host PRNP genotype. These findings demonstrate vitro-amplification assays provide enhanced advanced peripheral cervids, potential role spike substrate genotype efficiency.