Evaluation of antemortem diagnostic techniques in goats naturally infected with scrapie

Authors: MAMMADOVA, NAJIBA - Orise Fellow; WEST GREENLEE, HEATHER - Iowa State University; MOORE, JO - Orise Fellow; Hwang, Soyoun; Lehmkuhl, Aaron; Nicholson, Eric; Greenlee, Justin

Submitted to: Frontiers in Veterinary Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/12/2020
Publication Date: 11/6/2020
Citation: Mammadova, N., West Greenlee, H.M., Moore, J.S., Hwang, S., Lehmkuhl, A.D., Nicholson, E.M., Greenlee, J.J. 2020. Evaluation of antemortem diagnostic techniques in goats naturally infected with scrapie. Frontiers in Veterinary Science. 7. Article 517862. https://doi.org/10.3389/fvets.2020.517862.
DOI: https://doi.org/10.3389/fvets.2020.517862

Interpretive Summary: Scrapie is a prion disease that can infect sheep and goats, leading to irreversible brain damage and death. While natural scrapie in sheep has been widely described, less is known about naturally acquired goat scrapie. Additionally, animals infected with scrapie are generally not diagnosed until the onset of obvious clinical signs, therefore a reliable method to screen asymptomatic animals may aid in diagnosis. The first objective of this study was to better understand/characterize the different facets of natural goat scrapie (i.e., incubation period, clinical signs, patterns of abnormal prion protein accumulation in the central nervous system and peripheral tissues, and molecular profile). The second objective of this study was to evaluate the efficacy of antemortem assessment of retinal thickness, and analysis of recto-anal mucosa-associated lymphoid tissue (RAMALT) biopsies as a pre-clinical test to detect asymptomatic goats positive for the classical scrapie agent. Changes in retinal thickness have been reported in asymptomatic cattle infected with prion disease, and antemortem rectal biopsy has been previously described to be effective in identifying sheep and deer naturally infected with prion disease. Our results showed that rectal biopsy was 78% effective in identifying goats naturally infected with scrapie. We also found no detectable changes in retinal thickness over the course of the observation period. Early identification of goats infected with scrapie is important to goat herders and regulators with roles in scrapie diagnosis for the purpose of eradicating scrapie.

Technical Abstract: Scrapie is a naturally occurring transmissible spongiform encephalopathy (TSE) that affects sheep and goats. Sheep and goats can be infected with scrapie as lambs or kids via contact with the placenta or placental fluids, or from ingestion of prions shed in the environment and/or bodily fluids (e.g., saliva, urine, and feces). Like other TSEs, scrapie is generally not diagnosed before extensive and irreversible brain damage has occurred. Therefore, a reliable method to screen animals may facilitate diagnosis. Additionally, while natural scrapie in sheep has been widely described, naturally acquired goat scrapie is less well characterized. The purpose of this study was to better understand natural goat scrapie in regard to disease phenotype (i.e., incubation period, clinical signs, neuroanatomical deposition patterns of PrPSc, and molecular profile as detected by western blot); and to evaluate the efficacy of antemortem tests to detect scrapie positive animals in a herd of goats. Briefly, 28 scrapie-exposed goats were removed from a farm depopulated due to previous diagnoses of scrapie on the premises, and observed daily for 30 months. Over the course of the observation period, antemortem biopsies of recto-anal mucosa-associated lymphoid tissue (RAMALT) were taken and tested using immunohistochemistry and real-time quaking induced conversion (RT-QuIC), and retinal thickness was measured in vivo using optical coherence tomography (OCT). Following the observation period, immunohistochemistry and western blot were performed to assess neuroanatomical deposition patterns of PrPSc and molecular profile. Our results demonstrate that antemortem rectal biopsy was 78% effective in identifying goats naturally infected with scrapie, and that a positive antemortem rectal biopsy was associated with the presence of clinical signs of neurologic disease and a positive dam status. We report that changes in retinal thickness are not detectable over the course of the observation period in goats naturally infected with scrapie. Finally, our results indicate that the accumulation of PrPSc in central nervous system (CNS) and non-CNS tissues is consistent with previous reports of scrapie in sheep and goats.