The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform

Elizabeth S Williams - One of the best experts on this subject based on the ideXlab platform.

  • age related lesions in laboratory confined raccoons procyon lotor inoculated with the agent of Chronic Wasting Disease of mule deer
    Journal of Veterinary Diagnostic Investigation, 2007
    Co-Authors: Amir N Hamir, R C Cutlip, J M Miller, Robert A Kunkle, Juergen A Richt, Marcus E Kehrli, Elizabeth S Williams
    Abstract:

    This communication documents age-associated pathologic changes and final observations on experimental transmission of Chronic Wasting Disease (CWD) by the intracerebral route to raccoons (Procyon lotor). Four kits were inoculated intracerebrally with a brain suspension from mule deer with CWD. Two uninoculated kits served as controls. One CWD-inoculated raccoon was humanely killed at 38 months after inoculation, and 1 control animal died at 68 months after inoculation. Both animals had lesions that were unrelated to transmissible spongiform encephalopathy. Six years after inoculation, none of the 3 remaining CWD-inoculated raccoons had shown clinical signs of neurologic disorder, and the experiment was terminated. Spongiform encephalopathy was not observed by light microscopy, and the presence of abnormal prion protein (PrPd) was not detected by either immunohistochemistry or Western blot techniques. Age- related lesions observed in these raccoons included islet-cell pancreatic amyloidosis (5/6), cystic e...

  • transmission of Chronic Wasting Disease of mule deer to suffolk sheep following intracerebral inoculation
    Journal of Veterinary Diagnostic Investigation, 2006
    Co-Authors: Amir N Hamir, Elizabeth S Williams, R C Cutlip, J M Miller, Robert A Kunkle, Juergen A Richt
    Abstract:

    To determine the transmissibility of Chronic Wasting Disease (CWD) to sheep, 8 Suffolk lambs of various prion protein genotypes (4 ARQ/ARR, 3 ARQ/ARQ, 1 ARQ/VRQ at codons 136, 154, and 171, respectively) were inoculated intracerebrally with brain suspension from mule deer with CWD (CWD md ). Two other lambs were kept as noninoculated controls. Within 36 months postinoculation (MPI), 2 inoculated animals became sick and were euthanized. Only 1 sheep (euthanized at 35 MPI) showed clinical signs that were consistent with those described for scrapie. Microscopic lesions of spongiform encephalopathy (SE) were only seen in this sheep, and its tissues were determined to be positive for the abnormal prion protein (PrP res )b y immunohistochemistry and Western blot. Three other inoculated sheep were euthanized (36 to 60 MPI) because of conditions unrelated to TSE. The 3 remaining inoculated sheep and the 2 control sheep did not have clinical signs of Disease at the termination of the study (72 MPI) and were euthanized. Of the 3 remaining inoculated sheep, 1 was found to have SE, and its tissues were positive for PrP res . The sheep with clinical prion Disease (euthanized at 35 MPI) was of the heterozygous genotype (ARQ/VRQ), and the sheep with subclinical Disease (euthanized at 72 MPH) was of the homozygous ARQ/ARQ genotype. These findings demonstrate that transmission of the CWD md agent to sheep via the intracerebral route is possible. Interestingly, the host genotype may play a notable part in successful transmission and incubation period of CWD md .

  • Chronic Wasting Disease
    Veterinary Pathology, 2005
    Co-Authors: Elizabeth S Williams
    Abstract:

    Chronic Wasting Disease (CWD) is a unique transmissible spongiform encephalopathy (TSE) of mule deer (Odocoileus hemionus), white-tailed deer (O. virginianus), and Rocky Mountain elk (Cervus elaphus nelsoni). The natural history of CWD is incompletely understood, but it differs from scrapie and bovine spon- giform encephalopathy (BSE) by virtue of its occurrence in nondomestic and free-ranging species. CWD has many features in common with scrapie, including early widespread distribution of Disease-associated prion protein (PrP d ) in lymphoid tissues, with later involvement of central nervous system (CNS) and peripheral tissues. This distribution likely contributes to apparent efficiency of horizontal transmission and, in this, is similar to scrapie and differs from BSE. Clinical features and lesions of CWD are qualitatively similar to the other animal TSEs. Microscopically, marked spongiform lesions occur in the central nervous system (CNS) after a prolonged incubation period and variable course of clinical Disease. During incubation, PrP d can be identified in tissues by antibody-based detection systems. Although CWD can be transmitted by intracerebral inoculation to cattle, sheep, and goats, ongoing studies have not demonstrated that domestic livestock are susceptible via oral exposure, the presumed natural route of exposure to TSEs. Surveillance efforts for CWD in captive and free-ranging cervids will continue in concert with similar activities for scrapie and BSE. Erad- ication of CWD in farmed cervids is the goal of state, federal, and industry programs, but eradication of CWD from free-ranging populations of cervids is unlikely with currently available management techniques.

  • human land use influences Chronic Wasting Disease prevalence in mule deer
    Ecological Applications, 2005
    Co-Authors: Matthew L Farnsworth, Mary M Conner, Lisa L Wolfe, Thompson N Hobbs, Kenneth P Burnham, Elizabeth S Williams, David M Theobald, Michael W. Miller
    Abstract:

    Human alteration of landscapes can affect the distribution, abundance, and behavior of wildlife. We explored the effects of human land use on the prevalence of Chronic Wasting Disease (CWD) in mule deer (Odocoileus hemionus) populations residing in north-central Colorado. We chose best approximating models estimating CWD prevalence in relation to differences in human land use, sex, and geographic location. Prevalence was higher in developed areas and among male deer, suggesting anthropogenic influences on the occurrence of Disease. We also found a relatively high degree of variation in prevalence across the three study sites, suggesting that spatial patterns in Disease may be influenced by other factors operating at a broader, landscape scale. Our results suggest that multiple factors, including changes in land use, differences in exposure risk between sexes, and landscape-scaled heterogeneity, are associated with CWD prevalence in north-central Colorado.

  • transmission of prions from mule deer and elk with Chronic Wasting Disease to transgenic mice expressing cervid prp
    Journal of Virology, 2004
    Co-Authors: Shawn Browning, Candace K Mathiason, Gary L. Mason, Elizabeth S Williams, Michael W. Miller, Tanya Seward, Michael A Green, Gwyneth A J Eliason, Ed Hoover, Glenn C Telling
    Abstract:

    We generated mice expressing cervid prion protein to produce a transgenic system simulating Chronic Wasting Disease (CWD) in deer and elk. While normal mice were resistant to CWD, these transgenic mice uniformly developed signs of neurological dysfunction ∼230 days following intracerebral inoculation with four CWD isolates. Inoculated transgenic mice homozygous for the transgene array developed Disease after ∼160 days. The brains of sick transgenic mice exhibited widespread spongiform degeneration and contained abnormal prion protein and abundant amyloid plaques, many of which were florid plaques. Transmission studies indicated that the same prion strain caused CWD in the analyzed mule deer and elk. These mice provide a new and reliable tool for detecting CWD prions.

Michael W. Miller - One of the best experts on this subject based on the ideXlab platform.

  • susceptibilities of nonhuman primates to Chronic Wasting Disease
    Emerging Infectious Diseases, 2009
    Co-Authors: Brent Race, Michael W. Miller, Kimberly Meadewhite, Kent D Barbian, Richard Rubenstein, Giuseppe Lafauci, Larisa Cervenakova, Cynthia Favara, Donald J Gardner, Dan Long
    Abstract:

    Chronic Wasting Disease (CWD) is a transmissible spongiform encephalopathy, or prion Disease, that affects deer, elk, and moose. Human susceptibility to CWD remains unproven despite likely exposure to CWD-infected cervids. We used 2 nonhuman primate species, cynomolgus macaques and squirrel monkeys, as human models for CWD susceptibility. CWD was inoculated into these 2 species by intracerebral and oral routes. After intracerebral inoculation of squirrel monkeys, 7 of 8 CWD isolates induced a clinical Wasting syndrome within 33–53 months. The monkeys’ brains showed spongiform encephalopathy and protease-resistant prion protein (PrPres) diagnostic of prion Disease. After oral exposure, 2 squirrel monkeys had PrPres in brain, spleen, and lymph nodes at 69 months postinfection. In contrast, cynomolgus macaques have not shown evidence of clinical Disease as of 70 months postinfection. Thus, these 2 species differed in susceptibility to CWD. Because humans are evolutionarily closer to macaques than to squirrel monkeys, they may also be resistant to CWD.

  • a natural case of Chronic Wasting Disease in a free ranging moose alces alces shirasi
    Journal of Wildlife Diseases, 2007
    Co-Authors: Laurie A Baeten, Terry R Spraker, B E Powers, Jean E Jewell, Michael W. Miller
    Abstract:

    Chronic Wasting Disease (CWD) was diagnosed in a free-ranging moose (Alces alces shirasi) killed by a hunter in Jackson County, Colorado, USA, in September 2005. The diagnosis was based upon immunohistochemistry (IHC) demonstrating the presence of accumulations of CWD-associated prion protein (PrPCWD) in tissue sections of medulla oblongata at the level of the obex (dorsal motor nucleus of the vagus) and in retropharyngeal lymph node (RPLN); additional testing by IHC revealed deposits of PrPCWD in multiple sections of medulla oblongata and cervical spinal cord as well as palatine tonsil and submandibular lymph node tissues. Western blot confirmed the presence of PrPCWD in RPLN and tonsil tissue. The PrPCWD also was detected via enzyme-linked immunosorbent assay of RPLN tissue. Spongiform encephalopathy was observed in sections of the brainstem and cervical spinal cord, although no clinical signs were noted by the hunter who killed the animal. The affected moose was homozygous for methionine at codon 209 o...

  • a meta baci approach for evaluating management intervention on Chronic Wasting Disease in mule deer
    Ecological Applications, 2007
    Co-Authors: Mary M Conner, Michael W. Miller, Michael R Ebinger, Kenneth P Burnham
    Abstract:

    Advances in acquiring and analyzing the spatial attributes of data have greatly enhanced the potential utility of wildlife Disease surveillance data for addressing problems of ecological or economic importance. We present an approach for using wildlife Disease surveillance data to identify areas for (or of ) intervention, to spatially delineate paired treatment and control areas, and then to analyze these nonrandomly selected sites in a meta-analysis framework via before–after–control–impact (BACI) estimates of effect size. We apply these methods to evaluate the effectiveness of attempts to reduce Chronic Wasting Disease (CWD) prevalence through intensive localized culling of mule deer (Odocoileus hemionus) in north-central Colorado, USA. Areas where surveillance data revealed high prevalence or case clusters were targeted by state wildlife management agency personnel for focal scale (on average <17 km2) culling, primarily via agency sharpshooters. Each area of sustained culling that we could also identif...

  • linking Chronic Wasting Disease to mule deer movement scales a hierarchical bayesian approach
    Ecological Applications, 2006
    Co-Authors: Matthew L Farnsworth, Thompson N Hobbs, Jennifer A Hoeting, Michael W. Miller
    Abstract:

    Observed spatial patterns in natural systems may result from processes acting across multiple spatial and temporal scales. Although spatially explicit data on processes that generate ecological patterns, such as the distribution of Disease over a landscape, are frequently unavailable, information about the scales over which processes operate can be used to understand the link between pattern and process. Our goal was to identify scales of mule deer (Odocoileus hemionus) movement and mixing that exerted the greatest influence on the spatial pattern of Chronic Wasting Disease (CWD) in northcentral Colorado, USA. We hypothesized that three scales of mixing (individual, winter subpopulation, or summer subpopulation) might control spatial variation in Disease prevalence. We developed a fully Bayesian hierarchical model to compare the strength of evidence for each mixing scale. We found strong evidence that the finest mixing scale corresponded best to the spatial distribution of CWD infection. There was also evidence that land ownership and habitat use play a role in exacerbating the Disease, along with the known effects of sex and age. Our analysis demonstrates how information on the scales of spatial processes that generate observed patterns can be used to gain insight when process data are sparse or unavailable.

  • prions in skeletal muscles of deer with Chronic Wasting Disease
    Science, 2006
    Co-Authors: Rachel Angers, Christina J Sigurdson, Edward A Hoover, Michael W. Miller, Shawn Browning, Tanya Seward, Glenn C Telling
    Abstract:

    The emergence of Chronic Wasting Disease (CWD) in deer and elk in an increasingly wide geographic area, as well as the interspecies transmission of bovine spongiform encephalopathy to humans in the form of variant Creutzfeldt Jakob Disease, have raised concerns about the zoonotic potential of CWD. Because meat consumption is the most likely means of exposure, it is important to determine whether skeletal muscle of Diseased cervids contains prion infectivity. Here bioassays in transgenic mice expressing cervid prion protein revealed the presence of infectious prions in skeletal muscles of CWD-infected deer, demonstrating that humans consuming or handling meat from CWD-infected deer are at risk to prion exposure.

Michael D Samuel - One of the best experts on this subject based on the ideXlab platform.

  • mineral licks as environmental reservoirs of Chronic Wasting Disease prions
    PLOS ONE, 2018
    Co-Authors: Ian H Plummer, Chad J Johnson, Alexandra R Chesney, Joel A Pedersen, Michael D Samuel
    Abstract:

    Chronic Wasting Disease (CWD) is a fatal neurodegenerative Disease of deer, elk, moose, and reindeer (cervids) caused by misfolded prion proteins. The Disease has been reported across North America and recently discovered in northern Europe. Transmission of CWD in wild cervid populations can occur through environmental routes, but limited ability to detect prions in environmental samples has prevented the identification of potential transmission "hot spots". We establish widespread CWD prion contamination of mineral licks used by free-ranging cervids in an enzootic area in Wisconsin, USA. We show mineral licks can serve as reservoirs of CWD prions and thus facilitate Disease transmission. Furthermore, mineral licks attract livestock and other wildlife that also obtain mineral nutrients via soil and water consumption. Exposure to CWD prions at mineral licks provides potential for cross-species transmission to wildlife, domestic animals, and humans. Managing deer use of mineral licks warrants further consideration to help control outbreaks of CWD.

  • temporal patterns of Chronic Wasting Disease prion excretion in three cervid species
    Journal of General Virology, 2017
    Co-Authors: Ian H Plummer, Chad J Johnson, Joel A Pedersen, Scott D Wright, Michael D Samuel
    Abstract:

    Chronic Wasting Disease (CWD) is the only naturally occurring transmissible spongiform encephalopathy affecting free-ranging wildlife populations. Transmission of CWD occurs by direct contact or through contaminated environments; however, little is known about the temporal patterns of CWD prion excretion and shedding in wild cervids. We tested the urine and faeces of three species of captive cervids (elk, mule and white-tailed deer) at 6, 12, 18 and 24 months after oral inoculation to evaluate the temporal, species- and genotype-specific factors affecting the excretion of CWD prions. Although none of the animals exhibited clinical signs of CWD during the study, we determined that all three cervid species were excreting CWD prions by 6 months post-inoculation. Faecal samples were consistently positive for CWD prions for all three cervid species (88 %), and were more likely to be positive than urine samples (28 %). Cervids with genotypes encoding for the prion protein (PRNP) that were considered to be more susceptible to CWD were more likely to excrete CWD prions (94 %) than cervids with genotypes considered to be less susceptible (64 %). All cervids with CWD prions in their urine also had positive faeces (n=5), but the converse was not true. Our study is the first to demonstrate CWD prion excretion in urine by asymptomatic elk and mule deer. Our results indicate that the excretion of CWD prions in faeces and, to a lesser extent, urine may provide an important avenue for depositing prions in the environment.

  • Chronic Wasting Disease in white tailed deer infection mortality and implications for heterogeneous transmission
    Ecology, 2016
    Co-Authors: Michael D Samuel, Daniel J Storm
    Abstract:

    Chronic Wasting Disease (CWD) is a fatal neurodegenerative Disease affecting free-ranging and captive cervids that now occurs in 24 U.S. states and two Canadian provinces. Despite the potential threat of CWD to deer populations, little is known about the rates of infection and mortality caused by this Disease. We used epidemiological models to estimate the force of infection and Disease-associated mortality for white-tailed deer in the Wisconsin and Illinois CWD outbreaks. Models were based on age-prevalence data corrected for bias in aging deer using the tooth wear and replacement method. Both male and female deer in the Illinois outbreak had higher corrected age-specific prevalence with slightly higher female infection than deer in the Wisconsin outbreak. Corrected ages produced more complex models with different infection and mortality parameters than those based on apparent prevalence. We found that adult male deer have a more than threefold higher risk of CWD infection than female deer. Males also had higher Disease mortality than female deer. As a result, CWD prevalence was twofold higher in adult males than females. We also evaluated the potential impacts of alternative contact structures on transmission dynamics in Wisconsin deer. Results suggested that transmission of CWD among male deer during the nonbreeding season may be a potential mechanism for producing higher rates of infection and prevalence characteristically found in males. However, alternatives based on high environmental transmission and transmission from females to males during the breeding season may also play a role.

  • deer density and Disease prevalence influence transmission of Chronic Wasting Disease in white tailed deer
    Ecosphere, 2013
    Co-Authors: Daniel J Storm, Bryan J Richards, Robert E Rolley, Michael D Samuel, Paul Shelton, Nicholas S Keuler, Timothy R Van Deelen
    Abstract:

    Host-parasite dynamics and strategies for managing infectious Diseases of wildlife depend on the functional relationship between Disease transmission rates and host density. However, the Disease transmission function is rarely known for free-living wildlife, leading to uncertainty regarding the impacts of Diseases on host populations and effective control actions. We evaluated the influence of deer density, landscape features, and soil clay content on transmission of Chronic Wasting Disease (CWD) in young (<2-year-old) white-tailed deer (Odocoileus virginianus) in south-central Wisconsin, USA. We evaluated how frequency-dependent, density-dependent, and intermediate transmission models predicted CWD incidence rates in harvested yearling deer. An intermediate transmission model, incorporating both Disease prevalence and density of infected deer, performed better than simple density- and frequency-dependent models. Our results indicate a combination of social structure, non-linear relationships between infectious contact and deer density, and distribution of Disease among groups are important factors driving CWD infection in young deer. The landscape covariates % deciduous forest cover and forest edge density also were positively associated with infection rates, but soil clay content had no measurable influences on CWD transmission. Lack of strong density-dependent transmission rates indicates that controlling CWD by reducing deer density will be difficult. The consequences of non-linear Disease transmission and aggregation of Disease on cervid populations deserves further consideration.

  • the role of genetics in Chronic Wasting Disease of north american cervids
    Prion, 2012
    Co-Authors: Stacie J Robinson, Katherine I Orourke, Michael D Samuel, Chad J Johnson
    Abstract:

    Chronic Wasting Disease (CWD) is a major concern for the management of North American cervid populations. This fatal prion Disease has led to declines in populations which have high CWD prevalence and areas with both high and low infection rates have experienced economic losses in wildlife recreation and fears of potential spill-over into livestock or humans. Research from human and veterinary medicine has established that the prion protein gene (Prnp) encodes the protein responsible for transmissible spongiform encephalopathies (TSEs). Polymorphisms in the Prnp gene can lead to different prion forms that moderate individual susceptibility to and progression of TSE infection. Prnp genes have been sequenced in a number of cervid species including those currently infected by CWD (elk, mule deer, white-tailed deer, moose) and those for which susceptibility is not yet determined (caribou, fallow deer, sika deer). Over thousands of sequences examined, the Prnp gene is remarkably conserved within the family Cervidae; only 16 amino acid polymorphisms have been reported within the 256 amino acid open reading frame in the third exon of the Prnp gene. Some of these polymorphisms have been associated with lower rates of CWD infection and slower progression of clinical CWD. Here we review the body of research on Prnp genetics of North American cervids. Specifically, we focus on known polymorphisms in the Prnp gene, observed genotypic differences in CWD infection rates and clinical progression, mechanisms for genetic TSE resistance related to both the cervid host and the prion agent and potential for natural selection for CWD-resistance. We also identify gaps in our knowledge that require future research.

Edward A Hoover - One of the best experts on this subject based on the ideXlab platform.

  • detection of Chronic Wasting Disease prions in fetal tissues of free ranging white tailed deer
    bioRxiv, 2021
    Co-Authors: Amy V Nalls, Edward A Hoover, Erin Mcnulty, A Mayfield, J M Crum, M K Keel, Mark G Ruder, Candace K Mathiason
    Abstract:

    Abstract The transmission of Chronic Wasting Disease (CWD) has largely been attributed to contact with infectious prions shed in excretions (saliva, urine, feces, blood) by direct animal-to-animal exposure or indirect contact with the environment. Less-well studied has been the role mother-to-offspring transmission may play in the facile transmission of CWD. We asked whether such extensive spread may also be due to mother-to-offspring transmission, perhaps before birth. We thereby focused on a population of white-tailed deer from West Virginia, USA, in which CWD has been detected. Fetal tissues, ranging from 113 to 158 days of gestation, were harvested from the uteri of CWD+ dams in the asymptomatic phase of infection. Using serial protein misfolding amplification (sPMCA), we detected evidence of prion seeds in 6 of 14 in utero harvested fetuses, with earliest detection at 113 gestational days. This is the first report of CWD detection in free ranging white-tailed deer fetal tissues. Further investigation within cervid populations across North America will help define the role and impact of mother-to-offspring vertical transmission of CWD.

  • Pathways of Prion Spread during Early Chronic Wasting Disease in Deer
    Journal of Virology, 2017
    Co-Authors: Clare E Hoover, Nathaniel D. Denkers, Kristen A. Davenport, Mark D. Zabel, Davin M Henderson, Candace K Mathiason, Claudio Soto, Edward A Hoover
    Abstract:

    Among prion infections, two scenarios of prion spread are generally observed: (i) early lymphoid tissue replication or (ii) direct neuroinvasion without substantial antecedent lymphoid amplification. In nature, cervids are infected with Chronic Wasting Disease (CWD) prions by oral and nasal mucosal exposure, and studies of early CWD pathogenesis have implicated pharyngeal lymphoid tissue as the earliest sites of prion accumulation. However, knowledge of chronological events in prion spread during early infection remains incomplete. To investigate this knowledge gap in early CWD pathogenesis, we exposed white-tailed deer to CWD prions by mucosal routes and performed serial necropsies to assess PrP CWD tissue distribution by real-time quaking-induced conversion (RT-QuIC) and tyramide signal amplification immunohistochemistry (TSA-IHC). Although PrP CWD was not detected by either method in the initial days (1 and 3) postexposure, we observed PrP CWD seeding activity and follicular immunoreactivity in oropharyngeal lymphoid tissues at 1 and 2 months postexposure (MPE). At 3 MPE, PrP CWD replication had expanded to all systemic lymphoid tissues. By 4 MPE, the PrP CWD burden in all lymphoid tissues had increased and approached levels observed in terminal Disease, yet there was no evidence of nervous system invasion. These results indicate the first site of CWD prion entry is in the oropharynx, and the initial phase of prion amplification occurs in the oropharyngeal lymphoid tissues followed by rapid dissemination to systemic lymphoid tissues. This lymphoid replication phase appears to precede neuroinvasion. IMPORTANCE Chronic Wasting Disease (CWD) is a universally fatal transmissible spongiform encephalopathy affecting cervids, and natural infection occurs through oral and nasal mucosal exposure to infectious prions. Terminal Disease is characterized by PrP CWD accumulation in the brain and lymphoid tissues of affected animals. However, the initial sites of prion accumulation and pathways of prion spread during early CWD infection remain unknown. To investigate the chronological events of early prion pathogenesis, we exposed deer to CWD prions and monitored the tissue distribution of PrP CWD over the first 4 months of infection. We show CWD uptake occurs in the oropharynx with initial prion replication in the draining oropharyngeal lymphoid tissues, rapidly followed by dissemination to systemic lymphoid tissues without evidence of neuroinvasion. These data highlight the two phases of CWD infection: a robust prion amplification in systemic lymphoid tissues prior to neuroinvasion and establishment of a carrier state.

  • longitudinal detection of prion shedding in saliva and urine by Chronic Wasting Disease infected deer by real time quaking induced conversion
    Journal of Virology, 2015
    Co-Authors: Davin M Henderson, Nathaniel D. Denkers, Clare E Hoover, Candace K Mathiason, Nina C Garbino, Edward A Hoover
    Abstract:

    ABSTRACT Chronic Wasting Disease (CWD) is an emergent, rapidly spreading prion Disease of cervids. Shedding of infectious prions in saliva and urine is thought to be an important factor in CWD transmission. To help to elucidate this issue, we applied an in vitro amplification assay to determine the onset, duration, and magnitude of prion shedding in longitudinally collected saliva and urine samples from CWD-exposed white-tailed deer. We detected prion shedding as early as 3 months after CWD exposure and sustained shedding throughout the Disease course. We estimated that the 50% lethal dose (LD 50 ) for cervidized transgenic mice would be contained in 1 ml of infected deer saliva or 10 ml of urine. Given the average course of infection and daily production of these body fluids, an infected deer would shed thousands of prion infectious doses over the course of CWD infection. The direct and indirect environmental impacts of this magnitude of prion shedding on cervid and noncervid species are surely significant. IMPORTANCE Chronic Wasting Disease (CWD) is an emerging and uniformly fatal prion Disease affecting free-ranging deer and elk and is now recognized in 22 U.S. states and 2 Canadian provinces. It is unique among prion Diseases in that it is transmitted naturally through wild populations. A major hypothesis to explain CWD9s florid spread is that prions are shed in excreta and transmitted via direct or indirect environmental contact. Here we use a rapid in vitro assay to show that infectious doses of CWD prions are in fact shed throughout the multiyear Disease course in deer. This finding is an important advance in assessing the risks posed by shed CWD prions to animals as well as humans.

  • Chronic Wasting Disease of cervids current knowledge and future perspectives
    Annual Review of Animal Biosciences, 2015
    Co-Authors: Nicholas J Haley, Edward A Hoover
    Abstract:

    A naturally occurring transmissible spongiform encephalopathy (TSE) of mule deer was first reported in Colorado and Wyoming in 1967 and has since spread to other members of the cervid family in 22 states, 2 Canadian provinces, and the Republic of Korea. Chronic Wasting Disease (CWD), caused by exposure to an abnormally folded isoform of the cellular prion protein, is characterized by progressive neurological Disease in susceptible natural and experimental hosts and is ultimately fatal. CWD is thought to be transmitted horizontally in excreta and through contaminated environments, features common to scrapie of sheep, though rare among TSEs. Evolving detection methods have revealed multiple strains of CWD and with continued development may lead to an effective antemortem test. Managing the spread of CWD, through the development of a vaccine or environmental cleanup strategies, is an active area of interest. As such, CWD represents a unique challenge in the study of prion Diseases.

  • prion seeding activity in cerebrospinal fluid of deer with Chronic Wasting Disease
    PLOS ONE, 2013
    Co-Authors: Nicholas J Haley, Kristen A. Davenport, Davis M Seelig, Davin M Henderson, Candace K Mathiason, Alexandra Van De Motter, Scott Carver, Edward A Hoover
    Abstract:

    Transmissible spongiform encephalopathies (TSEs), or prion Diseases, are a uniformly fatal family of neurodegenerative Diseases in mammals that includes Chronic Wasting Disease (CWD) of cervids. The early and ante-mortem identification of TSE-infected individuals using conventional western blotting or immunohistochemistry (IHC) has proven difficult, as the levels of infectious prions in readily obtainable samples, including blood and bodily fluids, are typically beyond the limits of detection. The development of amplification-based seeding assays has been instrumental in the detection of low levels of infectious prions in clinical samples. In the present study, we evaluated the cerebrospinal fluid (CSF) of CWD-exposed (n=44) and naive (n=4) deer (n=48 total) for CWD prions (PrPd) using two amplification assays: serial protein misfolding cyclic amplification with polytetrafluoroethylene beads (sPMCAb) and real-time quaking induced conversion (RT-QuIC) employing a truncated Syrian hamster recombinant protein substrate. Samples were evaluated blindly in parallel with appropriate positive and negative controls. Results from amplification assays were compared to one another and to obex immunohistochemistry, and were correlated to available clinical histories including CWD inoculum source (e.g. saliva, blood), genotype, survival period, and duration of clinical signs. We found that both sPMCAb and RT-QuIC were capable of amplifying CWD prions from cervid CSF, and results correlated well with one another. Prion seeding activity in either assay was observed in approximately 50% of deer with PrPd detected by IHC in the obex region of the brain. Important predictors of amplification included duration of clinical signs and time of first tonsil biopsy positive results, and ultimately the levels of PrPd identified in the obex by IHC. Based on our findings, we expect that both sPMCAb and RT-QuIC may prove to be useful detection assays for the detection of prions in CSF.

Terry R Spraker - One of the best experts on this subject based on the ideXlab platform.

  • Novel Type of Chronic Wasting Disease Detected in Moose (Alces alces), Norway.
    Emerging infectious diseases, 2018
    Co-Authors: Laura Pirisinu, Turid Vikoren, Jørn Våge, Linh Tran, Knut Madslien, Barbara Chiappini, Ilaria Vanni, Michele Angelo Di Bari, Gabriele Vaccari, Terry R Spraker
    Abstract:

    Chronic Wasting Disease (CWD) persists in cervid populations of North America and in 2016 was detected for the first time in Europe in a wild reindeer in Norway. We report the detection of CWD in 3 moose (Alces alces) in Norway, identified through a large scale surveillance program. The cases occurred in 13-14-year-old female moose, and we detected an abnormal form of prion protein (PrPSc) in the brain but not in lymphoid tissues. Immunohistochemistry revealed that the moose shared the same neuropathologic phenotype, characterized by mostly intraneuronal deposition of PrPSc. This pattern differed from that observed in reindeer and has not been previously reported in CWD-infected cervids. Moreover, Western blot revealed a PrPSc type distinguishable from previous CWD cases and from known ruminant prion Diseases in Europe, with the possible exception of sheep CH1641. These findings suggest that these cases in moose represent a novel type of CWD.

  • human prion protein sequence elements impede cross species Chronic Wasting Disease transmission
    Journal of Clinical Investigation, 2015
    Co-Authors: Timothy D Kurt, Terry R Spraker, Lin Jiang, Natalia Fernandezborges, Cyrus Bett, Jun Liu, Tom Yang, Joaquin Castilla, David Eisenberg, Qingzhong Kong
    Abstract:

    Chronic Wasting Disease (CWD) is a fatal prion Disease of North American deer and elk and poses an unclear risk for transmission to humans. Human exposure to CWD occurs through hunting activities and consumption of venison from prion-infected animals. Although the amino acid residues of the prion protein (PrP) that prevent or permit human CWD infection are unknown, NMR-based structural studies suggest that the β2-α2 loop (residues 165-175) may impact species barriers. Here we sought to define PrP sequence determinants that affect CWD transmission to humans. We engineered transgenic mice that express human PrP with four amino acid substitutions that result in expression of PrP with a β2-α2 loop (residues 165-175) that exactly matches that of elk PrP. Compared with transgenic mice expressing unaltered human PrP, mice expressing the human-elk chimeric PrP were highly susceptible to elk and deer CWD prions but were concurrently less susceptible to human Creutzfeldt-Jakob Disease prions. A systematic in vitro survey of amino acid differences between humans and cervids identified two additional residues that impacted CWD conversion of human PrP. This work identifies amino acids that constitute a substantial structural barrier for CWD transmission to humans and helps illuminate the molecular requirements for cross-species prion transmission.

  • experimental oral transmission of Chronic Wasting Disease to reindeer rangifer tarandus tarandus
    PLOS ONE, 2012
    Co-Authors: Gordon Mitchell, Christina J Sigurdson, James Algire, Noel P Harrington, Ines Walther, Katherine I Orourke, Terry R Spraker, Aru Balachandran
    Abstract:

    Chronic Wasting Disease (CWD), a transmissible spongiform encephalopathy of cervids, remains prevalent in North American elk, white-tailed deer and mule deer. A natural case of CWD in reindeer (Rangifer tarandus tarandus) has not been reported despite potential habitat overlap with CWD-infected deer or elk herds. This study investigates the experimental transmission of CWD from elk or white-tailed deer to reindeer by the oral route of inoculation. Ante-mortem testing of the three reindeer exposed to CWD from white-tailed deer identified the accumulation of pathological PrP (PrPCWD) in the recto-anal mucosa associated lymphoid tissue (RAMALT) of two reindeer at 13.4 months post-inoculation. Terminal CWD occurred in the two RAMALT-positive reindeer at 18.5 and 20 months post-inoculation while one other reindeer in the white-tailed deer CWD inoculum group and none of the 3 reindeer exposed to elk CWD developed Disease. Tissue distribution analysis of PrPCWD in CWD-affected reindeer revealed widespread deposition in central and peripheral nervous systems, lymphoreticular tissues, the gastrointestinal tract, neuroendocrine tissues and cardiac muscle. Analysis of prion protein gene (PRNP) sequences in the 6 reindeer identified polymorphisms at residues 2 (V/M), 129 (G/S), 138 (S/N) and 169 (V/M). These findings demonstrate that (i) a sub-population of reindeer are susceptible to CWD by oral inoculation implicating the potential for transmission to other Rangifer species, and (ii) certain reindeer PRNP polymorphisms may be protective against CWD infection.

  • Association analysis of PRNP gene region with Chronic Wasting Disease in Rocky Mountain elk
    BMC Research Notes, 2010
    Co-Authors: Stephen N. White, Terry R Spraker, James O Reynolds, Katherine I O'rourke
    Abstract:

    Background Chronic Wasting Disease (CWD) is a transmissible spongiform encephalopathy (TSE) of cervids including white-tailed ( Odocoileus virginianus ) and mule deer ( Odocoileus hemionus ), Rocky Mountain elk ( Cervus elaphus nelsoni ), and moose ( Alces alces ). A leucine variant at position 132 (132L) in prion protein of Rocky Mountain elk confers a long incubation time with CWD, but not complete resistance. However, variants in regulatory regions outside the open reading frame of PRNP have been associated with varying degrees of susceptibility to prion Disease in other species, and some variants have been observed in similar regions of Rocky Mountain elk PRNP . Thus, additional genetic variants might provide increased protection, either alone or in combination with 132L. Findings This study provided genomic sequence of all exons for PRNP of Rocky Mountain elk. Many functional sites in and around the PRNP gene region were sequenced, and this report approximately doubled (to 75) the number of known variants in this region. A haplotype-tagging approach was used to reduce the number of genetic variants required to survey this variation in the PRNP gene region of 559 Rocky Mountain elk. Eight haplotypes were observed with frequencies over 1.0%, and one haplotype was present at 71.2% frequency, reflecting limited genetic diversity in the PRNP gene region. Conclusions The presence of 132L cut odds of CWD by more than half (Odds Ratio = 0.43; P = 0.0031), which was similar to a previous report. However after accounting for 132L, no association with CWD was found for any additional variants in the PRNP region (P > 0.05).

  • increased risk of Chronic Wasting Disease in rocky mountain elk associated with decreased magnesium and increased manganese in brain tissue
    Canadian Journal of Veterinary Research-revue Canadienne De Recherche Veterinaire, 2010
    Co-Authors: Stephen N. White, Katherine I Orourke, Kurt C Vercauteren, Thomas Gidlewski, Michelle R Mousel, Gregory E Phillips, Terry R Spraker
    Abstract:

    Chronic Wasting Disease (CWD) is a transmissible spongiform encephalopathy (TSE) of Rocky Mountain elk in North America. Recent studies suggest that tissue and blood mineral levels may be valuable in assessing TSE infection in sheep and cattle. The objectives of this study were to examine baseline levels of copper, manganese, magnesium, zinc, selenium, and molybdenum in the brains of Rocky Mountain elk with differing prion genotypes and to assess the association of mineral levels with CWD infection. Elk with leucine at prion position 132 had significantly lower magnesium levels than elk with 2 copies of methionine. Chronic Wasting Disease-positive elk had significantly lower magnesium than control elk. The incorporation of manganese levels in addition to magnesium significantly refined explanatory ability, even though manganese alone was not significantly associated with CWD. This study demonstrated that mineral analysis may provide an additional Disease correlate for assessing CWD risk, particularly in conjunction with genotype.