COS 44-5
Prion amplification and hierarchical Bayesian modeling refine detection and prevalence estimates of chronic wasting disease in a free-ranging elk population
Immunohistochemistry (IHC) is currently considered the gold standard for diagnosis of a prion infection. However, IHC may be insensitive to early or sub-clinical cases of prion infection that are important to understanding chronic wasting (CWD) disease transmission and ecology. We assessed the potential of serial protein misfolding cyclic amplification (sPMCA) to amplify and improve detection of prion infection prior to the onset of CWD. We obtained tissue samples from free-ranging Rocky Mountain elk (Cervus elaphus nelsoni) and used hierarchical Bayesian analysis to estimate the specificity and sensitivity of IHC and sPMCA conditional on simultaneously estimated disease states.
Results/Conclusions
Sensitivity estimates were higher for a single replicate of sPMCA (94.4%, credible interval (CI) 82.2-99.8%) than IHC evaluation (71.6%, CI 51.0-88.2%) of obex tissue. Only by testing obex as well as retropharyngeal and submandibular lymph nodes did IHC sensitivity (95.8%, 87.9-99.3%) compare to sPMCA. Sensitivity of sPMCA further improved with two or more replicates, resulting in >99% sensitivity. Our hierarchical Bayesian model predicts the CWD prevalence in this elk population to be 23.3% (CI 15.5-32.7%), compared to previous estimates of 13%. Our data reveal a previously unidentified sub-clinical prion-positive portion of the elk population that could represent silent carriers capable of prion transmission.