{"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":1791556068365,"version":"4.3.4"},"reference-count":25,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2023,3,30]],"date-time":"2023-03-30T00:00:00Z","timestamp":1680134400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"funder":[{"DOI":"10.13039\/100007917","name":"Agricultural Research Service","doi-asserted-by":"publisher","award":["2090-32000-042-000-D"],"award-info":[{"award-number":["2090-32000-042-000-D"]}],"id":[{"id":"10.13039\/100007917","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Chronic wasting disease (CWD) continues to spread in wild and farmed cervid populations. Early antemortem CWD testing of farmed cervids is of considerable interest to producers and regulatory agencies as a tool to combat this spread. The tissues accessible for antemortem sampling are limited and include biopsy of the tonsil and recto-anal mucosa-associated lymphoid tissue (RAMALT). The sensitivity to detect CWD by immunohistochemistry (IHC)\u2014the regulatory gold standard\u2014using biopsy samples of RAMALT from naturally infected white-tailed deer (WTD) has been determined by several studies. However, similar information is lacking for tonsil biopsy. In this study, two-bite tonsil biopsies from 79 naturally infected farmed WTD were used to determine the diagnostic sensitivity of tonsil IHC compared to the official CWD status based on results from the medial retropharyngeal lymph nodes and obex. IHC detection of CWD by tonsil biopsy was compared to the result and follicle metrics from the contralateral whole tonsil. The sensitivity of two-bite tonsil biopsy for detecting CWD by IHC was 72% overall. When the stage of infection was considered, the sensitivity was 92% for deer in late preclinical infection but only 55% for early preclinical infection. For deer with early preclinical infection, the sensitivity for deer homozygous for the prion protein gene (<jats:italic>PRNP<\/jats:italic>) coding for glycine at codon 96 (GG) was 66% but only 30% when heterozygous for the serine substitution (GS). The results indicate that the sensitivity of two-bite tonsil biopsy in WTD, and consequently its potential utility as an antemortem diagnostic, is limited during early infection, especially in WTD heterozygous for the serine substitution at <jats:italic>PRNP<\/jats:italic> codon 96.<\/jats:p>","DOI":"10.1371\/journal.pone.0282356","type":"journal-article","created":{"date-parts":[[2023,3,30]],"date-time":"2023-03-30T17:38:58Z","timestamp":1680197938000},"page":"e0282356","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":8,"title":["Tonsil biopsy to detect chronic wasting disease in white-tailed deer (Odocoileus virginianus) by immunohistochemistry"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9659-6731","authenticated-orcid":true,"given":"David A.","family":"Schneider","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron D.","family":"Lehmkuhl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terry R.","family":"Spraker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert O.","family":"Dittmar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitch A.","family":"Lockwood","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Rollo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3337-9462","authenticated-orcid":true,"given":"Tracy A.","family":"Nichols","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,3,30]]},"reference":[{"issue":"1","key":"pone.0282356.ref001","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":"ES Williams","year":"1980","journal-title":"J Wildl Dis"},{"issue":"1","key":"pone.0282356.ref002","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 TR","year":"2002","journal-title":"J Vet Diagn Invest"},{"issue":"2","key":"pone.0282356.ref003","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1177\/104063870601800202","article-title":"Comparison of two automated immunohistochemical procedures for the diagnosis of scrapie in domestic sheep and chronic wasting disease in North American white-tailed deer (Odocoileus virginianus) and mule deer (Odocoileus hemionus).","volume":"18","author":"TV Baszler","year":"2006","journal-title":"J Vet Diagn Invest"},{"key":"pone.0282356.ref004","unstructured":"Chronic Wasting Disease (CWD) Program Standards. 2019:[1\u201392 pp.]. Available from: https:\/\/www.aphis.usda.gov\/animal_health\/animal_diseases\/cwd\/downloads\/cwd-program-standards.pdf."},{"issue":"1","key":"pone.0282356.ref005","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":"DP Keane","year":"2008","journal-title":"J Vet Diagn Invest"},{"issue":"5","key":"pone.0282356.ref006","doi-asserted-by":"crossref","first-page":"e62455","DOI":"10.1371\/journal.pone.0062455","article-title":"Intranasal inoculation of white-tailed deer (Odocoileus virginianus) with lyophilized chronic wasting disease prion particulate complexed to montmorillonite clay.","volume":"8","author":"TA Nichols","year":"2013","journal-title":"PLoS One."},{"issue":"2\u20133","key":"pone.0282356.ref007","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.jcpa.2005.08.001","article-title":"Detection of PrPSc in rectal biopsy and necropsy samples from sheep with experimental scrapie","volume":"134","author":"A Espenes","year":"2006","journal-title":"J Comp Pathol"},{"issue":"13","key":"pone.0282356.ref008","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1136\/vr.162.13.397","article-title":"Diagnosis of preclinical scrapie in live sheep by the immunohistochemical examination of rectal biopsies","volume":"162","author":"L Gonzalez","year":"2008","journal-title":"Vet Rec"},{"issue":"6","key":"pone.0282356.ref009","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1177\/104063870601800605","article-title":"Detection of PrPCWD in postmortem rectal lymphoid tissues in Rocky Mountain elk (Cervus elaphus nelsoni) infected with chronic wasting disease.","volume":"18","author":"TR Spraker","year":"2006","journal-title":"J Vet Diagn Invest"},{"issue":"5","key":"pone.0282356.ref010","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":"BV Thomsen","year":"2012","journal-title":"J Vet Diagn Invest"},{"issue":"Pt 7","key":"pone.0282356.ref011","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":"LL Wolfe","year":"2007","journal-title":"J Gen Virol"},{"issue":"4","key":"pone.0282356.ref012","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":"NJ Haley","year":"2016","journal-title":"J Clin Microbiol"},{"issue":"5","key":"pone.0282356.ref013","doi-asserted-by":"crossref","first-page":"1412","DOI":"10.1128\/JCM.02209-08","article-title":"Validation of use of rectoanal mucosa-associated lymphoid tissue for immunohistochemical diagnosis of chronic wasting disease in white-tailed deer (Odocoileus virginianus).","volume":"47","author":"D Keane","year":"2009","journal-title":"J Clin Microbiol"},{"issue":"2","key":"pone.0282356.ref014","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":"RJ Monello","year":"2013","journal-title":"J Wildl Dis"},{"issue":"2","key":"pone.0282356.ref015","doi-asserted-by":"crossref","first-page":"e0228327","DOI":"10.1371\/journal.pone.0228327","article-title":"Progression of chronic wasting disease in white-tailed deer analyzed by serial biopsy RT-QuIC and immunohistochemistry.","volume":"15","author":"DM Henderson","year":"2020","journal-title":"PLoS One."},{"issue":"Pt 5","key":"pone.0282356.ref016","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1099\/vir.0.039073-0","article-title":"Sensitivity of protein misfolding cyclic amplification versus immunohistochemistry in ante-mortem detection of chronic wasting disease","volume":"93","author":"NJ Haley","year":"2012","journal-title":"J Gen Virol"},{"issue":"5","key":"pone.0282356.ref017","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":"DP Keane","year":"2008","journal-title":"J Vet Diagn 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Schuler","year":"2005","journal-title":"J Wildl Dis"},{"issue":"Pt 10","key":"pone.0282356.ref021","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":"MA Wild","year":"2002","journal-title":"J Gen Virol"},{"issue":"3","key":"pone.0282356.ref022","doi-asserted-by":"crossref","first-page":"276","DOI":"10.11613\/BM.2012.031","article-title":"Interrater reliability: the kappa statistic.","volume":"22","author":"ML McHugh","year":"2012","journal-title":"Biochem Med (Zagreb)."},{"issue":"4","key":"pone.0282356.ref023","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":"NJ Haley","year":"2016","journal-title":"J Clin Microbiol"},{"issue":"1","key":"pone.0282356.ref024","doi-asserted-by":"crossref","first-page":"17241","DOI":"10.1038\/s41598-017-17090-x","article-title":"Detection of Prions in Blood of Cervids at the Asymptomatic Stage of Chronic Wasting Disease.","volume":"7","author":"C Kramm","year":"2017","journal-title":"Sci Rep"},{"issue":"1","key":"pone.0282356.ref025","doi-asserted-by":"crossref","first-page":"19763","DOI":"10.1038\/s41598-020-75681-7","article-title":"Chronic wasting disease (CWD) prion detection in blood from pre-symptomatic white-tailed deer harboring PRNP polymorphic variants.","volume":"10","author":"C Kramm","year":"2020","journal-title":"Sci Rep"}],"container-title":["PLOS 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