Impact of Age and Sex of Rocky Mountain Elk (<i>Cervus Elaphus Nelsoni</i>) on Follicle Counts from Rectal Mucosal Biopsies for Preclinical Detection of Chronic Wasting Disease

Spraker, Terry R.; VerCauteren, Kurt C.; Gidlewski, Thomas; Munger, Randy D.; Walter, W. David; Balachandran, Aru

doi:10.1177/104063870902100618

Cited by 11 publications

(5 citation statements)

References 12 publications

(34 reference statements)

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“…7 Fewer lymph follicles are also found within rectal biopsy samples collected from older animals. 3,16 In the present study, the percentage of samples with an insufficient number of follicles occurred at an unexpectedly high rate (44%) in Canada herd 3, while the other 3 herds had rates of 9–17%, which is similar to a previous study. 7 Because the procedure causes minimal discomfort to the animal, the procedure is often performed using only restraint in proper animal handling facilities and topical anesthesia.…”

Section: Discussionsupporting

confidence: 90%

Diagnostic accuracy of rectal mucosa biopsy testing for chronic wasting disease within white-tailed deer (Odocoileus virginianus) herds in North America

et al. 2012

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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.

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Section: Discussionsupporting

confidence: 90%

Diagnostic accuracy of rectal mucosa biopsy testing for chronic wasting disease within white-tailed deer (Odocoileus virginianus) herds in North America

et al. 2012

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“…It has been tentatively suggested that at least 10 follicles are needed to obtain accurate diagnostic results from a rectal biopsy (Spraker et al, 2009a, b). Because follicle counts decline with age, most samples from elk that are older than 8 yr cannot meet this requirement (Spraker et al, 2009a). We suggest that for population-level inferences there is no need to obtain a minimum number of follicles because modern methods of hierarchic modeling (Clark and Gelfand, 2006) allow uncertainty associated with diagnosis to be included in a statistically appropriate way to estimate quantities of interest such as prevalence (see also Wolfe et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

Efficacy of Antemortem Rectal Biopsies to Diagnose and Estimate Prevalence of Chronic Wasting Disease in Free-Ranging Cow Elk (Cervus Elaphus Nelsoni)

Monello

Powers

Hobbs

et al. 2013

Journal of Wildlife Diseases

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ABSTRACT:A reliable antemortem test is needed to understand the ecology of chronic wasting disease (CWD) in elk (Cervus elaphus nelsoni). We measured the ability of antemortem biopsy samples from the rectal mucosa to detect the abnormal prion protein associated with CWD (PrP CWD ), the relationship between test results from the obex and rectal biopsies at varying stages of CWD progression, and the prevalence of CWD in free-ranging elk from Rocky Mountain National Park, Colorado, USA. We sampled and placed radio collars on 136 adult female elk in the winter of 2007-08. Elk with biopsy samples found positive for PrP CWD by immunohistochemistry (IHC) were euthanized and the obex and retropharyngeal lymph nodes were examined with IHC. We resampled, euthanized, and necropsied 20, 25, and 34 of the remaining study elk in each of the three following winters, respectively. Sensitivity of rectal biopsy samples increased in an asymptotic fashion with follicle count and was maximized at 85% (95% credible limits [CL]560, 98) in the beginning of the study, when a greater proportion of elk were in a detectable stage of prion infection. However, maximum sensitivity was reduced to 72% (CL546, 94) when we included resampled elk, which included recently infected elk that were initially negative using rectal biopsies and IHC. Test results were similar between rectal biopsies and the obex, but the earliest stages of prion infection were only detected by using retropharyngeal lymph nodes. Minimum CWD prevalence was estimated to be 9.9% (CL55.7, 15.7) using rectal biopsies, but this rose to 12.9% (CL58.0, 19.1) when we included four elk that were likely misdiagnosed at initial capture. Our results indicate rectal biopsies can provide a useful research tool for CWD in elk populations, but should be used with caution because they can miss individuals in early stages of infection and underestimate prevalence. Prevalence estimates from this population are the highest reported to date in elk and indicate that under appropriate conditions, CWD may be able to affect the dynamics of high-density elk populations.

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“…To date, preclinical testing for PrP CWD utilizes immunohistochemistry (IHC) of the palatine tonsils or rectal lymphoid tissues in cervids. 18,21,24 However, IHC does not routinely detect very early cases of CWD in these tissues. 17,20 Various fluids, such as saliva, blood, urine, and cerebrospinal fluid (CSF) have been evaluated in animals for their use in preclinical antemortem detection of abnormal prions.…”

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Detection of prion protein in the cerebrospinal fluid of elk (Cervus canadensis nelsoni) with chronic wasting disease using protein misfolding cyclic amplification

Nichols

Spraker²,

Gidlewski³

et al. 2012

J VET Diagn Invest

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Abstract. Cerebrospinal fluid (CSF) has been examined as a possible source for preclinical diagnosis of prion diseases in hamsters and sheep. The present report describes the detection of chronic wasting disease (CWD) in the CSF of elk and evaluates its usefulness as an antemortem test for CWD. The CSF from 6 captive and 31 free-ranging adult elk was collected at necropsy and evaluated for the presence of the abnormal isoform of the prion protein that has been associated with CWD (PrP CWD ) via protein misfolding cyclic amplification. Additionally, the obex from each animal was examined by immunohistochemistry (IHC). Four out of 6 captive animals were CWD-positive and euthanized due to signs of terminal CWD. The remaining 2 were CWD negative. None of the 31 free-range animals showed overt signs of CWD, but 12 out of 31 tested positive for CWD by IHC. Protein misfolding cyclic amplification detected PrP CWD from 3 of the 4 captive animals showing clinical signs of CWD and none of the nonclinical animals that were CWD positive by IHC. The data suggests that CWD prions can be detected in the CSF of elk, but only relatively late in the course of the disease.

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Impact of Age and Sex of Rocky Mountain Elk (Cervus Elaphus Nelsoni) on Follicle Counts from Rectal Mucosal Biopsies for Preclinical Detection of Chronic Wasting Disease

Cited by 11 publications

References 12 publications

Diagnostic accuracy of rectal mucosa biopsy testing for chronic wasting disease within white-tailed deer (Odocoileus virginianus) herds in North America

Diagnostic accuracy of rectal mucosa biopsy testing for chronic wasting disease within white-tailed deer (Odocoileus virginianus) herds in North America

Efficacy of Antemortem Rectal Biopsies to Diagnose and Estimate Prevalence of Chronic Wasting Disease in Free-Ranging Cow Elk (Cervus Elaphus Nelsoni)

Detection of prion protein in the cerebrospinal fluid of elk (Cervus canadensis nelsoni) with chronic wasting disease using protein misfolding cyclic amplification

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