title: Prion amplification and hierarchical Bayesian modeling refine detection of prion infection.
abstract: Prions are unique infectious agents that replicate without a genome and cause neurodegenerative diseases that include chronic wasting disease (CWD) of cervids. Immunohistochemistry (IHC) is currently considered the gold standard for diagnosis of a prion infection but may be insensitive to early or sub-clinical CWD that are important to understanding CWD transmission and ecology. We assessed the potential of serial protein misfolding cyclic amplification (sPMCA) to improve detection of CWD prior to the onset of clinical signs. We analyzed 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. Sensitivity estimates were higher for sPMCA (99.51%, credible interval (CI) 97.15-100%) than IHC of obex (brain stem, 76.56%, CI 57.00-91.46%) or retropharyngeal lymph node (90.06%, CI 74.13-98.70%) tissues, or both (98.99%, CI 90.01-100%). Our hierarchical Bayesian model predicts the prevalence of prion infection in this elk population to be 18.90% (CI 15.50-32.72%), compared to previous estimates of 12.90%. Our data reveal a previously unidentified sub-clinical prion-positive portion of the elk population that could represent silent carriers capable of significantly impacting CWD ecology.
authors: 1] Colorado State University Prion Research Center, Department of Microbiology, Immunology and Pathology, College of Veterinary Medicine and Biomedical Sciences, Fort Collins, CO 80523, USA [2] National Wildlife Research Center, Wildlife Services, United States Department of Agriculture, La Porte Avenue, Fort Collins, CO 80521.
authors: A Christy
authors: AC
authors: Wyckoff
authors: Department of Biology, College of Natural Sciences, Colorado State University, Fort Collins, Co 80523.
authors: Nathan
authors: N
authors: Galloway
authors: Colorado State University Prion Research Center, Department of Microbiology, Immunology and Pathology, College of Veterinary Medicine and Biomedical Sciences, Fort Collins, CO 80523, USA.
authors: Crystal
authors: C
authors: Meyerett-Reid
authors: National Park Service, Biological Resource Management Division, 1201 Oakridge Drive, Fort Collins, CO 80525, USA.
authors: Jenny
authors: J
authors: Powers
authors: Colorado State University Prion Research Center, Department of Microbiology, Immunology and Pathology, College of Veterinary Medicine and Biomedical Sciences, Fort Collins, CO 80523, USA.
authors: Terry
authors: T
authors: Spraker
authors: National Park Service, Biological Resource Management Division, 1201 Oakridge Drive, Fort Collins, CO 80525, USA.
authors: Ryan J
authors: RJ
authors: Monello
authors: Colorado State University Prion Research Center, Department of Microbiology, Immunology and Pathology, College of Veterinary Medicine and Biomedical Sciences, Fort Collins, CO 80523, USA.
authors: Bruce
authors: B
authors: Pulford
authors: National Park Service, Biological Resource Management Division, 1201 Oakridge Drive, Fort Collins, CO 80525, USA.
authors: Margaret
authors: M
authors: Wild
authors: Department of Biology, College of Natural Sciences, Colorado State University, Fort Collins, Co 80523.
authors: Michael
authors: M
authors: Antolin
authors: National Wildlife Research Center, Wildlife Services, United States Department of Agriculture, La Porte Avenue, Fort Collins, CO 80521.
authors: Kurt
authors: K
authors: VerCauteren
authors: Colorado State University Prion Research Center, Department of Microbiology, Immunology and Pathology, College of Veterinary Medicine and Biomedical Sciences, Fort Collins, CO 80523, USA.
authors: Mark
authors: M
authors: Zabel
mesh_terms: D000818:Animals; D001499:Bayes Theorem; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D003670:Deer; D051379:Mice; D008954:Models, Biological; D011328:Prions / Q000378:metabolism*; D034081:Wasting Disease, Chronic / Q000175:diagnosis / Q000378:metabolism
chemical_list: D011328:Prions