Assessment of Prospective Preventive Therapies for Chronic Wasting Disease in Mule Deer

Wolfe, Lisa L.; Kocisko, David A.; Caughey, Byron; Miller, Michael W.

doi:10.7589/0090-3558-48.2.530

Cited by 14 publications

(14 citation statements)

References 16 publications

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“…Oral Cu supplementation increased liver Cu concentrations compared to controls but did not affect susceptibility to CWD or survival after natural exposure in the captive white-tailed deer we studied. This outcome is similar to outcomes of prior experimental attempts to prevent CWD in mule deer (Odocoileus hemionus) using pentosan polysulfate, tannic acid, or tetracycline hydrochloride as a prophylactic therapy (Wolfe et al 2012). Prevention of CWD via practical vaccination approaches has proven equally unrewarding (Pilon et al 2013;Wood et al 2018).…”

Section: Discussionsupporting

confidence: 70%

Effect of Oral Copper Supplementation on Susceptibility in White-Tailed Deer (Odocoileus Virginianus) to Chronic Wasting Disease

Wolfe

Conner

Miller

2020

Journal of Wildlife Diseases

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Chronic wasting disease (CWD) is an infectious disease, but reported associations suggest several metals-especially copper (Cu) and manganese-potentially play a role in this and other prion diseases. To assess the utility of dietary Cu supplementation in protecting white-tailed deer (Odocoileus virginianus) from CWD, we compared incidence and disease course among individuals naturally exposed to CWD while being maintained on sustained-release Cu boluses or unsupplemented (control). Oral Cu supplementation increased liver tissue Cu concentrations compared to controls but did not affect susceptibility to CWD or survival after natural exposure in the captive white-tailed deer we studied. Over the 27 mo study, 89% (8/9) of the Cu-supplemented deer and 86% (6/7) of control deer became CWD-infected. Survival to 27 mo postexposure did not differ between Cu-supplemented and control deer: model-averaged survival probabilities to 27 mo were 0.45-0.47 for all combinations of Cu treatment and PRNP gene haplotype presence. The PRNP gene haplotype influenced the probability of deer remaining biopsy negative for at least 17 mo but did not affect overall susceptibility.

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Section: Discussionsupporting

confidence: 70%

Effect of Oral Copper Supplementation on Susceptibility in White-Tailed Deer (Odocoileus Virginianus) to Chronic Wasting Disease

Wolfe

Conner

Miller

2020

Journal of Wildlife Diseases

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“…Previous investigations have demonstrated that infectious CWD prions are present in saliva [ 11 , 16 ], feces [ 14 , 15 ], urine [ 12 , 13 , 18 ], blood [ 11 , 27 ], and tissues [ 28 , 29 ], and that environmental exposure alone can initiate infection [ 5 , 30 ]. However, experimental demonstration of CWD prion seeding activity or infectivity in naturally contaminated soil remains elusive.…”

Section: Introductionmentioning

confidence: 99%

Very low oral exposure to prions of brain or saliva origin can transmit chronic wasting disease

et al. 2020

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The minimum infectious dose required to induce CWD infection in cervids remains unknown, as does whether peripherally shed prions and/or multiple low dose exposures are important factors in CWD transmission. With the goal of better understand CWD infection in nature, we studied oral exposures of deer to very low doses of CWD prions and also examined whether the frequency of exposure or prion source may influence infection and pathogenesis. We orally inoculated white-tailed deer with either single or multiple divided doses of prions of brain or saliva origin and monitored infection by serial longitudinal tissue biopsies spanning over two years. We report that oral exposure to as little as 300 nanograms (ng) of CWD-positive brain or to saliva containing seeding activity equivalent to 300 ng of CWD-positive brain, were sufficient to transmit CWD disease. This was true whether the inoculum was administered as a single bolus or divided as three weekly 100 ng exposures. However, when the 300 ng total dose was apportioned as 10, 30 ng doses delivered over 12 weeks, no infection occurred. While low-dose exposures to prions of brain or saliva origin prolonged the time from inoculation to first detection of infection, once infection was established, we observed no differences in disease pathogenesis. These studies suggest that the CWD minimum infectious dose approximates 100 to 300 ng CWD-positive brain (or saliva equivalent), and that CWD infection appears to conform more with a threshold than a cumulative dose dynamic.

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“…Ingestion of forage or water contaminated by secretions, excretions, or other sources, for example, CWD-infected carcasses (Miller et al, 2004), has long been thought the most plausible natural route. In addition to prions shed by an infectious host, central nervous and lymphoid tissues (Sigurdson et al, 1999;Wolfe et al, 2012; also see Table 1) as well as many others (reviewed by Williams, 2005;Haley and Hoover, 2015) carry infectivity that may also represent sources of transmission if consumed by susceptible animals.…”

Section: Mechanisms Of Natural Transmissionmentioning

confidence: 99%

Chronic wasting disease (CWD) in cervids

Ricci¹,

Allende²,

Bolton³

et al. 2017

EFS2

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In April and May of 2016, Norway confirmed two cases of chronic wasting disease (CWD) in a wild reindeer and a wild moose, respectively. In the light of this emerging issue, the European Commission requested EFSA to recommend surveillance activities and, if necessary, additional animal health risk‐based measures to prevent the introduction of the disease and the spread into/within the EU, specifically Estonia, Finland, Iceland, Latvia, Lithuania, Norway, Poland and Sweden, and considering seven wild, semidomesticated and farmed cervid species (Eurasian tundra reindeer, Finnish (Eurasian) forest reindeer, moose, roe deer, white‐tailed deer, red deer and fallow deer). It was also asked to assess any new evidence on possible public health risks related to CWD. A 3‐year surveillance system is proposed, differing for farmed and wild or semidomesticated cervids, with a two‐stage sampling programme at the farm/geographically based population unit level (random sampling) and individual level (convenience sampling targeting high‐risk animals). The current derogations of Commission Implementing Decision (EU) 2016/1918 present a risk of introduction of CWD into the EU. Measures to prevent the spread of CWD within the EU are dependent upon the assumption that the disease is already present; this is currently unknown. The measures listed are intended to contain (limit the geographic extent of a focus) and/or to control (actively stabilise/reduce infection rates in an affected herd or population) the disease where it occurs. With regard to the zoonotic potential, the human species barrier for CWD prions does not appear to be absolute. These prions are present in the skeletal muscle and other edible tissues, so humans may consume infected material in enzootic areas. Epidemiological investigations carried out to date make no association between the occurrence of sporadic Creutzfeldt–Jakob disease in humans and exposure to CWD prions.

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Assessment of Prospective Preventive Therapies for Chronic Wasting Disease in Mule Deer

Cited by 14 publications

References 16 publications

Effect of Oral Copper Supplementation on Susceptibility in White-Tailed Deer (Odocoileus Virginianus) to Chronic Wasting Disease

Effect of Oral Copper Supplementation on Susceptibility in White-Tailed Deer (Odocoileus Virginianus) to Chronic Wasting Disease

Very low oral exposure to prions of brain or saliva origin can transmit chronic wasting disease

Chronic wasting disease (CWD) in cervids

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