{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T14:27:48Z","timestamp":1791556068182,"version":"4.3.4"},"reference-count":114,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2017,8,5]],"date-time":"2017-08-05T00:00:00Z","timestamp":1501891200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Since chronic wasting disease (CWD) was first identified nearly 50 years ago in a captive mule deer herd in the Rocky Mountains of the United States, it has slowly spread across North America through the natural and anthropogenic movement of cervids and their carcasses. As the endemic areas have expanded, so has the need for rapid, sensitive, and cost effective diagnostic tests\u2014especially those which take advantage of samples collected antemortem. Over the past two decades, strategies have evolved from the recognition of microscopic spongiform pathology and associated immunohistochemical staining of the misfolded prion protein to enzyme-linked immunoassays capable of detecting the abnormal prion conformer in postmortem samples. In a history that parallels the diagnosis of more conventional infectious agents, both qualitative and real-time amplification assays have recently been developed to detect minute quantities of misfolded prions in a range of biological and environmental samples. With these more sensitive and semi-quantitative approaches has come a greater understanding of the pathogenesis and epidemiology of this disease in the native host. Because the molecular pathogenesis of prion protein misfolding is broadly analogous to the misfolding of other pathogenic proteins, including A\u03b2 and \u03b1-synuclein, efforts are currently underway to apply these in vitro amplification techniques towards the diagnosis of Alzheimer\u2019s disease, Parkinson\u2019s disease, and other proteinopathies. Chronic wasting disease\u2014once a rare disease of Colorado mule deer\u2014now represents one of the most prevalent prion diseases, and should serve as a model for the continued development and implementation of novel diagnostic strategies for protein misfolding disorders in the natural host.<\/jats:p>","DOI":"10.3390\/pathogens6030035","type":"journal-article","created":{"date-parts":[[2017,8,9]],"date-time":"2017-08-09T06:32:14Z","timestamp":1502260334000},"page":"35","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":55,"title":["Evolution of Diagnostic Tests for Chronic Wasting Disease, a Naturally Occurring Prion Disease of Cervids"],"prefix":"10.3390","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0502-7862","authenticated-orcid":false,"given":"Nicholas","family":"Haley","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Arizona College of Osteopathic Medicine, Midwestern University, Glendale, AZ 85308, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7308-5672","authenticated-orcid":false,"given":"J\u00fcrgen","family":"Richt","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Kansas State University (KSU), Manhattan, KS 66506, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2017,8,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"89","DOI":"10.7589\/0090-3558-16.1.89","article-title":"Chronic wasting disease of captive mule deer: A spongiform encephalopathy","volume":"16","author":"Williams","year":"1980","journal-title":"J. Wildl. Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1146\/annurev-animal-022114-111001","article-title":"Chronic Wasting Disease of Cervids: Current Knowledge and Future Perspectives","volume":"3","author":"Haley","year":"2015","journal-title":"Annu. Rev. Anim. Biosci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1186\/s13567-016-0375-4","article-title":"First case of chronic wasting disease in Europe in a Norwegian free-ranging reindeer","volume":"47","author":"Benestad","year":"2016","journal-title":"Vet. Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"977","DOI":"10.3201\/eid1006.031082","article-title":"Chronic wasting disease and potential transmission to humans","volume":"10","author":"Belay","year":"2004","journal-title":"Emerg. Infect. Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/S0140-6736(03)15171-9","article-title":"Transmissible spongiform encephalopathies","volume":"363","author":"Collins","year":"2004","journal-title":"Lancet"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"7944","DOI":"10.1523\/JNEUROSCI.2467-05.2005","article-title":"Chronic wasting disease of elk: Transmissibility to humans examined by transgenic mouse models","volume":"25","author":"Kong","year":"2005","journal-title":"J. Neurosci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1624","DOI":"10.1099\/vir.0.042507-0","article-title":"Chronic wasting disease and atypical forms of bovine spongiform encephalopathy and scrapie are not transmissible to mice expressing wild-type levels of human prion protein","volume":"93","author":"Wilson","year":"2012","journal-title":"J. Gen. Virol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1099\/vir.0.046110-0","article-title":"Mucosal transmission and pathogenesis of chronic wasting disease in ferrets","volume":"94","author":"Perrott","year":"2012","journal-title":"J. Gen. Virol."},{"key":"ref_9","first-page":"210","article-title":"Chronic wasting disease (CWD) susceptibility of several North American rodents that are sympatric with cervid CWD epidemics","volume":"4","author":"Heisey","year":"2009","journal-title":"J. Virol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1292\/jvms.64.855","article-title":"A case of chronic wasting disease in an elk imported to Korea from Canada","volume":"64","author":"Sohn","year":"2002","journal-title":"J. Vet. Med. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"551","DOI":"10.2307\/3803123","article-title":"Chronic wasting disease of deer and elk: A review with recommendations for management","volume":"66","author":"Williams","year":"2002","journal-title":"J. Wildl. Manag."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1354\/vp.42-5-530","article-title":"Chronic wasting disease","volume":"42","author":"Williams","year":"2005","journal-title":"Vet. Pathol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Stokstad, E. (Science Magazine, 2017). Norway plans to exterminate a large reindeer herd to stop a fatal infectious brain disease, Science Magazine.","DOI":"10.1126\/science.aal0996"},{"key":"ref_14","unstructured":"Picard, J. (Oneida Daily Dispatch News, 2005). Experts explain deer disease, Oneida Daily Dispatch News."},{"key":"ref_15","unstructured":"Watts, T. (Oakland Press News, 2009). CWD leads to new regulations for taxidermists, Oakland Press News."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1126\/science.1122864","article-title":"Prions in skeletal muscles of deer with chronic wasting disease","volume":"311","author":"Angers","year":"2006","journal-title":"Science"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"9608","DOI":"10.1128\/JVI.01127-09","article-title":"Prion infectivity in fat of deer with chronic wasting disease","volume":"83","author":"Race","year":"2009","journal-title":"J. Virol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"696","DOI":"10.3201\/eid1505.081458","article-title":"Chronic wasting disease prions in elk antler velvet","volume":"15","author":"Angers","year":"2009","journal-title":"Emerg. Infect. Dis."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Haley, N.J., Seelig, D.M., Zabel, M.D., Telling, G.C., and Hoover, E.A. (2009). Detection of CWD prions in urine and saliva of deer by transgenic mouse bioassay. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0004848"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1126\/science.1132661","article-title":"Infectious prions in the saliva and blood of deer with chronic wasting disease","volume":"314","author":"Mathiason","year":"2006","journal-title":"Science"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1038\/nature08289","article-title":"Asymptomatic deer excrete infectious prions in faeces","volume":"461","author":"Tamguney","year":"2009","journal-title":"Nature"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0021-9975(85)90071-4","article-title":"Amyloid plaques in spongiform encephalopathy of mule deer","volume":"95","author":"Bahmanyar","year":"1985","journal-title":"J. Comp. Pathol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1007\/BF00454902","article-title":"Fibrils in brain of Rocky Mountain elk with chronic wasting disease contain scrapie amyloid","volume":"86","author":"Guiroy","year":"1993","journal-title":"Acta Neuropathol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/0304-3940(91)90552-5","article-title":"Immunolocalization of scrapie amyloid (PrP27-30) in chronic wasting disease of Rocky Mountain elk and hybrids of captive mule deer and white-tailed deer","volume":"126","author":"Guiroy","year":"1991","journal-title":"Neurosci. Lett."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1007\/BF00310125","article-title":"Topographic distribution of scrapie amyloid-immunoreactive plaques in chronic wasting disease in captive mule deer (Odocoileus hemionus hemionus)","volume":"81","author":"Guiroy","year":"1991","journal-title":"Acta Neuropathol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1177\/104063870301500402","article-title":"Field validation and assessment of an enzyme-linked immunosorbent assay for detecting chronic wasting disease in mule deer (Odocoileus hemionus), white-tailed deer (Odocoileus virginianus), and Rocky Mountain elk (Cervus elaphus nelsoni)","volume":"15","author":"Hibler","year":"2003","journal-title":"J. Vet. Diagn. Investig."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"8322","DOI":"10.1128\/JVI.00633-10","article-title":"Cell-based quantification of chronic wasting disease prions","volume":"84","author":"Bian","year":"2010","journal-title":"J. Virol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1016\/S0166-2236(02)02195-1","article-title":"Cyclic amplification of protein misfolding: Application to prion-related disorders and beyond","volume":"25","author":"Soto","year":"2002","journal-title":"Trends Neurosci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"9605","DOI":"10.1128\/JVI.00635-07","article-title":"Efficient in vitro amplification of chronic wasting disease PrPRES","volume":"81","author":"Kurt","year":"2007","journal-title":"J. Virol."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Wilham, J.M., Orru, C.D., Bessen, R.A., Atarashi, R., Sano, K., Race, B., Meade-White, K.D., Taubner, L.M., Timmes, A., and Caughey, B. (2010). Rapid end-point quantitation of prion seeding activity with sensitivity comparable to bioassays. PLoS Pathog., 6.","DOI":"10.1371\/journal.ppat.1001217"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1038\/nmeth1066","article-title":"Ultrasensitive detection of scrapie prion protein using seeded conversion of recombinant prion protein","volume":"4","author":"Atarashi","year":"2007","journal-title":"Nat. Methods"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3237","DOI":"10.1128\/JCM.01258-14","article-title":"Detection of chronic wasting disease in the lymph nodes of free-ranging cervids by real-time quaking-induced conversion","volume":"52","author":"Haley","year":"2014","journal-title":"J. Clin. Microbiol."},{"key":"ref_33","first-page":"193","article-title":"Chronic wasting disease of cervids","volume":"284","author":"Miller","year":"2004","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1016\/j.bbadis.2006.10.010","article-title":"Chronic wasting disease","volume":"1772","author":"Sigurdson","year":"2007","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1309","DOI":"10.1126\/science.6815801","article-title":"Identification of a protein that purifies with the scrapie prion","volume":"218","author":"Bolton","year":"1982","journal-title":"Science"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1126\/science.6801762","article-title":"Novel proteinaceous infectious particles cause scrapie","volume":"216","author":"Prusiner","year":"1982","journal-title":"Science"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"22753","DOI":"10.1038\/srep22753","article-title":"Emergence of a novel bovine spongiform encephalopathy (BSE) prion from an atypical H-type BSE","volume":"6","author":"Masujin","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1177\/104063870001200618","article-title":"Immunohistochemical diagnosis of chronic wasting disease in preclinically affected elk from a captive herd","volume":"12","author":"Peters","year":"2000","journal-title":"J. Vet. Diagn. Investig."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2757","DOI":"10.1099\/0022-1317-80-10-2757","article-title":"Oral transmission and early lymphoid tropism of chronic wasting disease PrPres in mule deer fawns (Odocoileus hemionus)","volume":"80","author":"Sigurdson","year":"1999","journal-title":"J. Gen. Virol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1177\/104063870802000110","article-title":"Comparison of retropharyngeal lymph node and obex region of the brainstem in detection of chronic wasting disease in white-tailed deer (Odocoileus virginianus)","volume":"20","author":"Keane","year":"2008","journal-title":"J. Vet. Diagn. Investig."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1177\/104063870802000534","article-title":"Chronic wasting disease in a Wisconsin white-tailed deer farm","volume":"20","author":"Keane","year":"2008","journal-title":"J. Vet. Diagn. Investig."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1136\/vr.155.10.295","article-title":"Variable patterns of distribution of PrP(CWD) in the obex and cranial lymphoid tissues of Rocky Mountain elk (Cervus elaphus nelsoni) with subclinical chronic wasting disease","volume":"155","author":"Spraker","year":"2004","journal-title":"Vet. Rec."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"3451","DOI":"10.1099\/vir.0.81999-0","article-title":"Patterns of PrPCWD accumulation during the course of chronic wasting disease infection in orally inoculated mule deer (Odocoileus hemionus)","volume":"87","author":"Fox","year":"2006","journal-title":"J. Gen. Virol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1128\/JCM.02700-15","article-title":"Seeded Amplification of Chronic Wasting Disease Prions in Nasal Brushings and Recto-anal Mucosa-Associated Lymphoid Tissues from Elk by Real-Time Quaking-Induced Conversion","volume":"54","author":"Haley","year":"2016","journal-title":"J. Clin. Microbiol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1108","DOI":"10.1128\/JCM.02699-15","article-title":"Antemortem Detection of Chronic Wasting Disease Prions in Nasal Brush Collections and Rectal Biopsy Specimens from White-Tailed Deer by Real-Time Quaking-Induced Conversion","volume":"54","author":"Haley","year":"2016","journal-title":"J. Clin. Microbiol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"878","DOI":"10.1177\/1040638712453582","article-title":"Diagnostic accuracy of rectal mucosa biopsy testing for chronic wasting disease within white-tailed deer (Odocoileus virginianus) herds in North America: Effects of age, sex, polymorphism at PRNP codon 96, and disease progression","volume":"24","author":"Thomsen","year":"2012","journal-title":"J. Vet. Diagn. Investig."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2617","DOI":"10.1099\/0022-1317-83-10-2617","article-title":"PrP(CWD) lymphoid cell targets in early and advanced chronic wasting disease of mule deer","volume":"83","author":"Sigurdson","year":"2002","journal-title":"J. Gen. Virol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2629","DOI":"10.1099\/0022-1317-83-10-2629","article-title":"Preclinical diagnosis of chronic wasting disease in captive mule deer (Odocoileus hemionus) and white-tailed deer (Odocoileus virginianus) using tonsillar biopsy","volume":"83","author":"Wild","year":"2002","journal-title":"J. Gen. Virol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1177\/104063870201400102","article-title":"Validation of monoclonal antibody F99\/97.6.1 for immunohistochemical staining of brain and tonsil in mule deer (Odocoileus hemionus) with chronic wasting disease","volume":"14","author":"Spraker","year":"2002","journal-title":"J. Vet. Diagn. Investig."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1177\/104063870902100103","article-title":"Antemortem detection of PrPCWD in preclinical, ranch-raised Rocky Mountain elk (Cervus elaphus nelsoni) by biopsy of the rectal mucosa","volume":"21","author":"Spraker","year":"2009","journal-title":"J. Vet. Diagn. Investig."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"676","DOI":"10.7589\/0090-3558-36.4.676","article-title":"Epizootiology of chronic wasting disease in free-ranging cervids in Colorado and Wyoming","volume":"36","author":"Miller","year":"2000","journal-title":"J. Wildl. Dis."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"305","DOI":"10.20506\/rst.21.2.1340","article-title":"Chronic wasting disease in deer and elk in North America","volume":"21","author":"Williams","year":"2002","journal-title":"Rev. Sci. Tech."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"578","DOI":"10.7589\/0090-3558-42.3.578","article-title":"Spatial epidemiology of chronic wasting disease in Wisconsin white-tailed deer","volume":"42","author":"Joly","year":"2006","journal-title":"J. Wildl. Dis."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.1080\/15287390903084249","article-title":"Surveillance for transmissible spongiform encephalopathy in scavengers of white-tailed deer carcasses in the chronic wasting disease area of Wisconsin","volume":"72","author":"Jennelle","year":"2009","journal-title":"J. Toxicol. Environ. Health A"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"369","DOI":"10.3201\/eid1803.110685","article-title":"Occurrence, transmission, and zoonotic potential of chronic wasting disease","volume":"18","author":"Saunders","year":"2012","journal-title":"Emerg. Infect. Dis."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2109","DOI":"10.1099\/vir.0.81615-0","article-title":"Prion protein polymorphisms in white-tailed deer influence susceptibility to chronic wasting disease","volume":"87","author":"Johnson","year":"2006","journal-title":"J. Gen. Virol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1935","DOI":"10.1097\/WNR.0b013e3282f1ca2f","article-title":"Elk with a long incubation prion disease phenotype have a unique PrPd profile","volume":"18","author":"Spraker","year":"2007","journal-title":"Neuroreport"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"28","DOI":"10.4161\/pri.2.1.6321","article-title":"Prion sequence polymorphisms and chronic wasting disease resistance in Illinois white-tailed deer (Odocoileus virginianus)","volume":"2","author":"Kelly","year":"2008","journal-title":"Prion"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"153","DOI":"10.4161\/pri.19640","article-title":"The role of genetics in chronic wasting disease of North American cervids","volume":"6","author":"Robinson","year":"2012","journal-title":"Prion"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2127","DOI":"10.1099\/vir.0.81077-0","article-title":"Low frequency of PrP genotype 225SF among free-ranging mule deer (Odocoileus hemionus) with chronic wasting disease","volume":"86","author":"Jewell","year":"2005","journal-title":"J. Gen. Virol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2765","DOI":"10.1099\/0022-1317-80-10-2765","article-title":"PrP genotypes of captive and free-ranging Rocky Mountain elk (Cervus elaphus nelsoni) with chronic wasting disease","volume":"80","author":"Besser","year":"1999","journal-title":"J. Gen. Virol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"576","DOI":"10.7589\/0090-3558-39.3.576","article-title":"Prion protein gene heterogeneity in free-ranging white-tailed deer within the chronic wasting disease affected region of Wisconsin","volume":"39","author":"Johnson","year":"2003","journal-title":"J. Wildl. Dis."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.3201\/eid1006.040010","article-title":"Environmental sources of prion transmission in mule deer","volume":"10","author":"Miller","year":"2004","journal-title":"Emerg. Infect. Dis."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"532","DOI":"10.7589\/0090-3558-34.3.532","article-title":"Epidemiology of chronic wasting disease in captive Rocky Mountain elk","volume":"34","author":"Miller","year":"1998","journal-title":"J. Wildl. Dis."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"13345","DOI":"10.1128\/JVI.78.23.13345-13350.2004","article-title":"Transmission of prions from mule deer and elk with chronic wasting disease to transgenic mice expressing cervid PrP","volume":"78","author":"Browning","year":"2004","journal-title":"J. Virol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"5097","DOI":"10.1128\/JVI.02169-09","article-title":"B cells and platelets harbor prion infectivity in the blood of deer infected with chronic wasting disease","volume":"84","author":"Mathiason","year":"2010","journal-title":"J. Virol."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Haley, N., Mathiason, C., Zabel, M.D., Telling, G.C., and Hoover, E. (2009). Detection of sub-clinical CWD infection in conventional test-negative deer long after oral exposure to urine and feces from CWD+ deer. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0007990"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1099\/vir.0.039073-0","article-title":"Sensitivity of protein misfolding cyclic amplification vs. immunohistochemistry in antemortem detection of CWD infection","volume":"93","author":"Haley","year":"2012","journal-title":"J. Gen. Virol."},{"key":"ref_69","unstructured":"(2014). Chronic Wasting Disease Program Standards."},{"key":"ref_70","unstructured":"Canadian Food Inspection Agency (2017). Accredited Veterinarian\u2019s Manual, Canadian Food Inspection Agency."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1099\/vir.0.069906-0","article-title":"Quantitative assessment of prion infectivity in tissues and body fluids by real-time quaking-induced conversion","volume":"96","author":"Henderson","year":"2015","journal-title":"J. Gen. Virol."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Henderson, D., Tennant, J., Haley, N., Denkers, N.D., Mathiason, C., and Hoover, E. (2017). Detection of CWD Prion-seeding Activity in Deer and Elk Feces by Real-time Quaking Induced Conversion. J. Gen. Virol., in press.","DOI":"10.1099\/jgv.0.000844"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"6309","DOI":"10.1128\/JVI.00425-11","article-title":"Detection of CWD prions in salivary, urinary, and intestinal tissues of deer: Potential mechanisms of prion shedding and transmission","volume":"85","author":"Haley","year":"2011","journal-title":"J. Virol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"e00077-17","DOI":"10.1128\/JVI.00077-17","article-title":"Pathways of Prion Spread during Early Chronic Wasting Disease in Deer","volume":"91","author":"Hoover","year":"2017","journal-title":"J. Virol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/S0076-6879(06)12001-7","article-title":"Protein misfolding cyclic amplification for diagnosis and prion propagation studies","volume":"412","author":"Castilla","year":"2006","journal-title":"Methods Enzymol."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Gonzalez-Montalban, N., Makarava, N., Ostapchenko, V.G., Savtchenk, R., Alexeeva, I., Rohwer, R.G., and Baskakov, I.V. (2011). Highly efficient protein misfolding cyclic amplification. PLoS Pathog., 7.","DOI":"10.1371\/journal.ppat.1001277"},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Haley, N.J., Van de Motter, A., Carver, S., Henderson, D., Davenport, K., Seelig, D.M., Mathiason, C., and Hoover, E. (2013). Prion-seeding activity in cerebrospinal fluid of deer with chronic wasting disease. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0081488"},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Park, J.H., Choi, Y.G., Park, S.J., Choi, H.S., Choi, E.K., and Kim, Y.S. (2017). Ultra-efficient Amplification of Abnormal Prion Protein by Modified Protein Misfolding Cyclic Amplification with Electric Current. Mol. Neurobiol.","DOI":"10.1007\/s12035-017-0431-8"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.jviromet.2009.02.019","article-title":"Surround optical fiber immunoassay (SOFIA): An ultra-sensitive assay for prion protein detection","volume":"159","author":"Chang","year":"2009","journal-title":"J. Virol. Methods"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1883","DOI":"10.1099\/vir.0.020164-0","article-title":"A novel method for preclinical detection of PrPSc in blood","volume":"91","author":"Rubenstein","year":"2010","journal-title":"J. Gen. Virol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"425","DOI":"10.7589\/0090-3558-48.2.425","article-title":"Detection of PrPCWD in feces from naturally exposed Rocky Mountain elk (Cervus elaphus nelsoni) using protein misfolding cyclic amplification","volume":"48","author":"Pulford","year":"2012","journal-title":"J. Wildl. Dis."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1177\/1040638712448060","article-title":"Detection of prion protein in the cerebrospinal fluid of elk (Cervus canadensis nelsoni) with chronic wasting disease using protein misfolding cyclic amplification","volume":"24","author":"Nichols","year":"2012","journal-title":"J. Vet. Diagn. Investig."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"5476","DOI":"10.1128\/JVI.00282-11","article-title":"Replication efficiency of soil-bound prions varies with soil type","volume":"85","author":"Saunders","year":"2011","journal-title":"J. Virol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"171","DOI":"10.4161\/pri.3.3.9819","article-title":"Detection of protease-resistant cervid prion protein in water from a CWD-endemic area","volume":"3","author":"Nichols","year":"2009","journal-title":"Prion"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1168","DOI":"10.1016\/j.celrep.2015.04.036","article-title":"Grass plants bind, retain, uptake, and transport infectious prions","volume":"11","author":"Pritzkow","year":"2015","journal-title":"Cell Rep."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/j.virol.2008.09.023","article-title":"In vitro strain adaptation of CWD prions by serial protein misfolding cyclic amplification","volume":"382","author":"Meyerett","year":"2008","journal-title":"Virology"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1038\/370471a0","article-title":"Cell-free formation of protease-resistant prion protein","volume":"370","author":"Kocisko","year":"1994","journal-title":"Nature"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1038\/nmeth0308-211","article-title":"Simplified ultrasensitive prion detection by recombinant PrP conversion with shaking","volume":"5","author":"Atarashi","year":"2008","journal-title":"Nat. Methods"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"9524","DOI":"10.1128\/JVI.01439-15","article-title":"Insights into Chronic Wasting Disease and Bovine Spongiform Encephalopathy Species Barriers by Use of Real-Time Conversion","volume":"89","author":"Davenport","year":"2015","journal-title":"J. Virol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1016\/j.ajpath.2011.05.057","article-title":"Chronic Wasting Disease Prion Trafficking via the Autonomic Nervous System","volume":"179","author":"Seelig","year":"2011","journal-title":"Am. J. Pathol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1002\/(SICI)1097-0320(19960101)23:1<48::AID-CYTO7>3.0.CO;2-I","article-title":"Immunofluorescence signal amplification by the enzyme-catalyzed deposition of a fluorescent reporter substrate (CARD)","volume":"23","author":"Chao","year":"1996","journal-title":"Cytometry"},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Henderson, D.M., Manca, M., Haley, N.J., Denkers, N.D., Nalls, A.V., Mathiason, C.K., Caughey, B., and Hoover, E.A. (2013). Rapid Antemortem Detection of CWD Prions in Deer Saliva. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0074377"},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Elder, A.M., Henderson, D.M., Nalls, A.V., Wilham, J.M., Caughey, B.W., Hoover, E.A., Kincaid, A.E., Bartz, J.C., and Mathiason, C.K. (2013). In Vitro Detection of prionemia in TSE-Infected Cervids and Hamsters. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0080203"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"7421","DOI":"10.1128\/JVI.00760-15","article-title":"Immediate and Ongoing Detection of Prions in the Blood of Hamsters and Deer following Oral, Nasal, or Blood Inoculations","volume":"89","author":"Elder","year":"2015","journal-title":"J. Virol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1228","DOI":"10.1128\/jcm.34.5.1228-1231.1996","article-title":"Immunohistochemical detection of prion protein in lymphoid tissues of sheep with natural scrapie","volume":"34","author":"Schreuder","year":"1996","journal-title":"J. Clin. Microbiol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1136\/vr.158.10.325","article-title":"Postmortem diagnosis of preclinical and clinical scrapie in sheep by the detection of disease-associated PrP in their rectal mucosa","volume":"158","author":"Gonzalez","year":"2006","journal-title":"Vet. Rec."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"3254","DOI":"10.1128\/JCM.38.9.3254-3259.2000","article-title":"Preclinical diagnosis of scrapie by immunohistochemistry of third eyelid lymphoid tissue","volume":"38","author":"Baszler","year":"2000","journal-title":"J. Clin. Microbiol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"982","DOI":"10.1038\/nm1286","article-title":"Detection of prions in blood","volume":"11","author":"Castilla","year":"2005","journal-title":"Nat. Med."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1126\/science.1129051","article-title":"Presymptomatic detection of prions in blood","volume":"313","author":"Saa","year":"2006","journal-title":"Science"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1177\/104063870601800605","article-title":"Detection of PrP(CWD) in postmortem rectal lymphoid tissues in Rocky Mountain elk (Cervus elaphus nelsoni) infected with chronic wasting disease","volume":"18","author":"Spraker","year":"2006","journal-title":"J. Vet. Diagn. Investig."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"2078","DOI":"10.1099\/vir.0.82342-0","article-title":"PrPCWD in rectal lymphoid tissue of deer (Odocoileus spp.)","volume":"88","author":"Wolfe","year":"2007","journal-title":"J. Gen. Virol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"270","DOI":"10.7589\/2011-12-362","article-title":"Efficacy of antemortem rectal biopsies to diagnose and estimate prevalence of chronic wasting disease in free-ranging cow elk (Cervus elaphus nelsoni)","volume":"49","author":"Monello","year":"2013","journal-title":"J. Wildl. Dis."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"250","DOI":"10.7589\/2012-07-174","article-title":"Effects of capture-related injury on postcapture movement of white-tailed deer","volume":"50","author":"Williams","year":"2014","journal-title":"J. Wildl. Dis."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"151","DOI":"10.4103\/0255-0857.150940","article-title":"Multiplex PCR in diagnosis of M. tuberculosis and M. avium co-infection from lymph node in an AIDS patient","volume":"33","author":"Sharma","year":"2015","journal-title":"Indian J. Med. Microbiol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1038\/sj.bdj.4810832","article-title":"Staphylococcus aureus in the oral cavity: A three-year retrospective analysis of clinical laboratory data","volume":"195","author":"Smith","year":"2003","journal-title":"Br. Dent. J."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1128\/jcm.30.4.786-789.1992","article-title":"Comparison of rapid methods of detection of cytomegalovirus in saliva with virus isolation in tissue culture","volume":"30","author":"Warren","year":"1992","journal-title":"J. Clin. Microbiol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1099\/vir.0.035006-0","article-title":"Evidence for distinct chronic wasting disease (CWD) strains in experimental CWD in ferrets","volume":"93","author":"Perrott","year":"2011","journal-title":"J. Gen. Virol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1154","DOI":"10.1126\/science.1187107","article-title":"Prion strain mutation determined by prion protein conformational compatibility and primary structure","volume":"328","author":"Angers","year":"2010","journal-title":"Science"},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"Orru, C.D., Groveman, B.R., Raymond, L.D., Hughson, A.G., Nonno, R., Zou, W., Ghetti, B., Gambetti, P., and Caughey, B. (2015). Bank Vole Prion Protein As an Apparently Universal Substrate for RT-QuIC-Based Detection and Discrimination of Prion Strains. PLoS Pathog., 11.","DOI":"10.1371\/journal.ppat.1004983"},{"key":"ref_110","doi-asserted-by":"crossref","unstructured":"Ayers, J.I., Giasson, B.I., and Borchelt, D.R. (2017). Prion-like Spreading in Tauopathies. Biol. Psychiatry.","DOI":"10.1016\/j.biopsych.2017.04.003"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1002\/ana.24098","article-title":"Do prions cause Parkinson disease?: The evidence accumulates","volume":"75","author":"Olanow","year":"2014","journal-title":"Ann. Neurol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/S1474-4422(17)30037-6","article-title":"The prion model for progression and diversity of neurodegenerative diseases","volume":"16","author":"Stopschinski","year":"2017","journal-title":"Lancet Neurol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"1137","DOI":"10.1016\/j.bbrc.2016.07.123","article-title":"Amyloid-beta and tau pathology following repetitive mild traumatic brain injury","volume":"483","author":"Edwards","year":"2017","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"2233","DOI":"10.1038\/nprot.2016.120","article-title":"The real-time quaking-induced conversion assay for detection of human prion disease and study of other protein misfolding diseases","volume":"11","author":"Schmitz","year":"2016","journal-title":"Nat. Protoc."}],"container-title":["Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-0817\/6\/3\/35\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T18:41:31Z","timestamp":1760208091000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-0817\/6\/3\/35"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,8,5]]},"references-count":114,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2017,9]]}},"alternative-id":["pathogens6030035"],"URL":"https:\/\/doi.org\/10.3390\/pathogens6030035","relation":{"has-preprint":[{"id-type":"doi","id":"10.20944\/preprints201707.0003.v1","asserted-by":"object"}]},"ISSN":["2076-0817"],"issn-type":[{"value":"2076-0817","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,8,5]]}}}