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

Authors: THOMSEN, BRUCE - Animal And Plant Health Inspection Service (APHIS); Schneider, David; O'Rourke, Katherine; GIDLEWSKI, THOMAS - Animal And Plant Health Inspection Service (APHIS); MCLANE, JAMES - Canadian Food Inspection Agency; ALLEN, ROBERT - Canadian Food Inspection Agency; MCISAAC, ALEX - Canadian Food Inspection Agency; MITCHELL, GORDON - Canadian Food Inspection Agency; KEANE, DELWYN - University Of Wisconsin; SPRAKER, TERRY - Colorado State University; BALACHANDRAN, ARU - Canadian Food Inspection Agency

Submitted to: J Vet Diagn Invest
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/26/2012
Publication Date: 9/1/2012
Citation: Thomsen, B.V., Schneider, D.A., O'Rourke, K., Gidlewski, T., Mclane, J., Allen, R.W., Mcisaac, A.A., Mitchell, G.B., Keane, D.P., Spraker, T., Balachandran, A. 2012. 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. J Vet Diagn Invest. 24(5):878-87.

Interpretive Summary: Control of prion diseases such as scrapie disease and chronic wasting disease (CWD) relies upon the use of accurate diagnostic testing methods. Biopsy of the rectal mucosa has proven to be an acceptable method of obtaining samples from live animals for the accurate diagnosis of scrapie in sheep and CWD in elk, and has shown promise for similar use in deer. The present study was a multi-national inter-agency effort to determine the diagnostic accuracy of testing based on samples obtained through biopsy of the rectal mucosa of deer and includes evaluation of over 600 white-tailed deer from 4 North American herds that were experiencing natural, subclinical CWD infection. Despite some limitation on sensitivity associated with early stage infection and with certain prion protein genotypes, it is concluded that selective use will provide regulatory veterinarians a useful live-animal method for investigating herds suspected of having subclinical CWD and with the potential of reducing the investigative costs based on current protocols.

Technical Abstract: An effective live animal diagnostic test is needed to assist in the control of chronic wasting disease (CWD), which has spread through captive and wild herds of white-tailed deer (Odocoileus virginianus) in Canada and the United States. In the present study, the diagnostic accuracy of rectal mucosa biopsy sample testing was determined in white-tailed deer from 4 CWD-infected captive herds. Specifically, the current study compared the immunohistochemical detection of disease-associated prion protein in postmortem rectal mucosa biopsy samples to the CWD status of each deer as determined by immunodiagnostic evaluations of the brainstem at the obex, the medial retropharyngeal lymph node, and the palatine tonsil. The effects of age, sex, genotype, and disease progression were also evaluated. Diagnostic sensitivity on rectal biopsy samples for CWD in white-tailed deer ranged from 63% to 100%; the pooled estimate of sensitivity was 68% with 95% confidence limits (95% CLs) of 49% and 82%. However, diagnostic sensitivity was dependent on genotype at prion protein gene (PRNP) codon 96 and on disease progression as assessed by obex grade. Diagnostic sensitivity was 76% (95% CLs: 49%, 91%) for 96GG deer but only 42% (95% CLs: 13%, 79%) for 96GS deer. Furthermore, diagnostic sensitivity was only 36% for deer in the earliest stage of disease (obex grade 0) but was 100% for deer in the last 2 stages of preclinical disease (obex grades 3 and 4). The overall diagnostic specificity was 99.8%. Selective use of antemortem rectal biopsy sample testing would provide valuable information during disease investigations of CWD-suspect deer herds.