NC1209: North American interdisciplinary chronic wasting disease research consortium

(Multistate Research Project)

Status: Active

NC1209: North American interdisciplinary chronic wasting disease research consortium

Duration: 10/01/2020 to 09/30/2025

Administrative Advisor(s):


NIFA Reps:


Non-Technical Summary

Statement of Issues and Justification

Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy (TSE), or prion disease, of North American deer and elk (cervids) (Williams 2005). Other TSEs include Creutzfeldt-Jakob disease in humans, bovine spongiform encephalopathy (“mad cow” disease) in cattle, and scrapie in sheep and goats. TSEs are inevitably fatal, progressive neurodegenerative diseases with long incubation periods and no known cure (Prusiner, 1982, 1998). Once believed to be isolated to the front range of the Rocky Mountains, since 2000 the known range of CWD has expanded dramatically to include 27 U.S. states, three Canadian provinces, Scandinavia, and South Korea. The range of the disease continues to expand, prevalence is increasing within endemic areas, and the disease has acquired new hosts (viz. moose and reindeer; Baeten et al. 2007, Benestad et al. 2016). In addition to affecting wild cervid populations, the occurrence of CWD in North America poses a potential risk to the agricultural industry, outdoor recreation, and human health. In states where CWD is established it has emerged as a major threat, reducing the health of deer populations and causing long-term population decline (Edmunds et al. 2016, Gross and Miller 2001, Manjerovic et al. 2014). Because the disease directly threatens North American cervid populations, it also challenges the fiscal foundations of wildlife conservation in the U.S. Sales of deer hunting licenses constitute a large proportion of annual revenue for conservation and management programs across taxa. Declines in these revenues due to CWD threatens the financial cornerstone of state fisheries and wildlife programs. Transmission to humans has not been documented, but the Centers for Disease Control and Prevention advises hunters to not consume the meat of infected animals because CWD is closely related to bovine spongiform encephalopathy, which has transmitted to humans and caused fatal human prion disease (CDC 2017). Uncertainties about human and livestock susceptibility, environmental contamination, and the ability of plants to accumulate the disease agent raise food and feed safety concerns (Hamir et al., 2011; Moore et al., 2017; Race et al 2009; 2018; Marsh et al., 2005; Pritzkow et al., 2015). Finally, emerging evidence is renewing concern that CWD may pose a risk to human health, and even perceptions that humans may become infected will have dramatic ecological and social consequences.


The infectious agent of CWD is a prion, an infectious, misfolded form of the normally benign prion protein. Misfolded prion protein accumulates in the brainstem and lymphatic tissue of infected animals, and to a lesser extent in muscle and other tissues (Sigurdson et al. 2002, Angers et al. 2006, Henderson et al. 2015a, Spraker et al. 2015, Davenport et al. 2018). The disease propagates via a process in which infectious, misfolded forms of the protein template the conformational conversion of the normal, benign form of the protein into the abnormal, disease-associated form (Prusiner, 1982;1998). This property of prions has been exploited to develop a variety of amplification assays that can be used to detect prions in tissues, secretions, excreta, and environmental samples (Haley et al. 2012, Henderson et al. 2015b, Pritzkow et al. 2015, Denkers et al. 2016, Henderson et al. 2017, Plummer et al. 2018).


Chronic wasting disease is transmitted directly through animal-to-animal contact and indirectly through contact with contaminated environments (Miller et al. 2004). Infected deer shed prions through secretions and excreta (Miller et al. 2004, Mathiason et al. 2006, Safar et al. 2008, Haley et al. 2009, Tamgüney et al. 2009), and human-facilitated movement of infected live deer or carcasses contributes to the geographic spread of CWD. Prion shedding by deer is poorly understood; shedding rate, time, and amounts need to be clarified. For example, transmission rates and mode (i.e., frequency- versus density-dependence transmission) for CWD have not been determined (Almberg et al. 2011). Epidemiological models specific to CWD and deer in highly productive habitats of the Midwest and Northeast are in early stages (Williams et al. 2014). Only the first steps have been taken towards understanding sites on the landscape where environmental transmission may occur (Plummer et al. 2018).


Prions shed into the environment remain infectious for years (Brown & Gajdusek. 1991, Miller et al. 2004, Georgsson et al. 2006, Seidel et al. 2007). Prions are remarkably resistant to most inactivation procedures that are effective against conventional infectious agents (e.g., many chemical disinfectants, autoclaving under conventional conductions, ionizing radiation, desiccation; Taylor 1999, Colby and Prusiner 2011). Some treatments are effective, at least in laboratory settings (e.g., concentrated hypochlorous acid, sodium hydroxide, peroxymonosulfate; Taylor 1999, Chesney et al. 2016, Williams et al. 2019). No cure exists for CWD (Smith et al. 2011, Xu et al. 2013), and vaccine development has proven difficult because the misfolded form of host-derived prion protein is not identified by the adaptive immune system as foreign (Goni et al. 2015). Deer shed prions long before they manifest any outward signs of CWD (e.g., emaciation, disorientation, fearlessness, paralysis; Henderson et al. 2015). Therefore, reducing environmental contamination would benefit from detection and removal of diseased deer from the environment well before clinical disease signs are exhibited.


Benefit of a Multistate Effort. Chronic wasting disease is distributed widely in North America, affects multiple cervid species, and does not respect jurisdictional boundaries. Research across multiple disciplines is needed to fully address the complexities of CWD and acquire the knowledge needed to limit or eliminate its spread. A multistate CWD effort to coordinate research across jurisdictions would be beneficial for several reasons.


·       The ecology of CWD is expected to differ across the regions and jurisdictions in which it occurs due to variation in species, climate, surficial geology, habitat, and land use.


·       Host prion protein genotype (Prnp) distribution varies geographically. While no genotype is known to confer complete resistance to CWD, susceptibility to the disease depends on Prnp genotype (Johnson et al. 2006). Host Prnp genotype can affect management strategies.


·       Prion strains vary geographically. Different strains of CWD exist and can be distinguished by the length of incubation period and Prnp polymorphism-dependent infectivity. Prion shedding into the environment by infected individuals may differ in magnitude or in dynamics by CWD strain (or host genotype). Strains may differ in their zoonotic potential and can affect management strategies.


·       A multistate effort could facilitate the coordination of resources. Resources could include funding for joint research efforts, sources of negative control animals or tissues, a clearinghouse for reference samples, large-scale research facilities, and increased capacity through a human resource network.


·       Jurisdictions impacted by CWD differ in their surveillance approaches. Standardization across jurisdictions would facilitate data sharing and increase epidemiological understanding of CWD dynamics.


·       Jurisdictions impacted by CWD differ in their legal authorities to minimize spread and resulting policy or management responses. Multi-state research provides the opportunity to assess the effectiveness of different regulatory strategies.


·       Disease management activities (or lack thereof) in one jurisdiction can affect the spread of the disease in another. Coordination across jurisdictional boundaries will improve the efficacy of disease surveillance and management and can enhance consistency and coordination between jurisdictions.


State and federal policies require public support and, frequently, funding for implementation. Given emerging research and perceptions around human health risk, as well as the growing footprint of CWD and CWD-related management, public health departments, natural resource agencies, and agricultural agencies are becoming increasingly involved with communication and public engagement regarding CWD. Understanding public attitudes, values, risk perceptions, and associated behavior will be critical for the development of socially accepted disease response strategies and effective strategies for addressing CWD. A multistate research project would facilitate sharing of data and resources, promote interdisciplinary collaboration among researchers and managers in different jurisdictions, and serve as a vehicle through which to communicate research and management priorities to national decision-makers. The multistate project would be designed to improve information exchange among universities and researchers with common goals, but different backgrounds and knowledge bases. Increased collaboration would improve research quality and avoid duplication of work at a critical time when effective solutions are needed quickly. Research on and management of CWD across North America is fragmented and not coordinated leading to issues of data comparability, duplication of effort, and concerns about the validity of measurements. The proposed multistate project would directly address these issues and both accelerate and improve the quality of CWD research and management nationally.


National and Regional Priorities. On September 9 and 10, the NCDC234 Multistate Research Coordinating Committee and Information Exchange Group held a facilitated 2-day workshop at Michigan State University to define research priorities, develop a list of action items to facilitate and coordinate research across states, and discuss the formation of a Multistate Research Project focused on chronic wasting disease. The workshop brought together 46 researchers and wildlife managers from 14 universities, 7 state agencies, 3 federal agencies, 1 Canadian province, and 1 non-governmental organization to identify critical research priorities informed by the needs of state and provincial CWD managers. Participants included both disease managers and university researchers from states currently affected by CWD and were selected based on their expertise in basic prion biology, prion measurement techniques, surveillance for human prion diseases, deer ecology, soil science, quantitative ecology, disease ecology, genetics, and policy. The workshop generated much enthusiasm for a Multistate Research Project and resulted in the prioritization of research topics and several action plans.


We guided workshop participants through a structured strategic planning process to identify and flesh out research priorities and critical activities that would benefit research on and management of CWD in North America. We developed clear pathways forward for establishing a collaborative of scientists and managers with consensus around research topic areas of immediate need. We intend to build upon this successful workshop and assemble interdisciplinary teams of researchers and partner agencies to develop research proposals around these prioritized research areas. This coordination helps address a critical need for the formation of a CWD research consortium focused on conducting research across multiple disciplines and jurisdictions to address the challenges of CWD. The workshop participants built consensus around and developed the following five thematic areas:


1.     Disease Transmission and Pathogenesis. Questions remain about indirect/environmental transmission of CWD prions and the persistence of prions in the environment. The structural basis for CWD prion strains is unknown. A multistate effort could help advance knowledge of CWD transmission and pathogenesis in several ways. Access to samples across regions would facilitate the characterization of strains and infectivity. A national CWD tissue and reagents bank could provide reference tissue samples to researchers across the nation to validate assays, improve comparability of inactivation studies. As the range of CWD expands, the acquisition of negative control samples is expected to become increasingly difficult. The multistate project could serve as a coordinating body for the distribution of verified negative control samples for researchers across the country. Cross-jurisdictional standardization of surveillance approaches and assays would facilitate data sharing.


2.     Development of Large-scale Research Facilities. Workshop participants identified the need for facilities to conduct controlled CWD research at scales better approximating those relevant for free-ranging cervids. An opportunity exists for developing such research facilities using fenced (depopulated) deer facilities. Large-scale research facilities could be used for studies on the impact of population demographics on transmission, possible habitat management options,, and remediation of environmental contamination. A multistate project could help establish these facilities and once formed solicit research proposals for the use of such facilities to advance knowledge on CWD disease dynamics and management that would have a significant impact for all countries affected by CWD.


3.     Improving Diagnostic Testing for CWD. Although assays to sensitively detect prions have improved rapidly in recent years, a rapid, inexpensive diagnostic test for live animals or environments does not exist or appear to be on the horizon, at least in the near to intermediate term (Haley and Richt. 2017). A transformative advance in the detection of prions has been the development of in vitro prion amplification assays, of which several variations have been developed. The most prominent are serial protein misfolding cyclic amplification (sPMCA) and real-time quaking-induced conversion (RT-QuIC). These assays may provide the needed foundation for advancing diagnostic testing of live animals and environments for presence of CWD prions. At present, RT-QuIC appears to be more suitable for adoption by federal and state agencies. Workshop participants identified a number of activities that could promote broader adoption of RT-QuIC and that a multistate effort could facilitate including coordination of provision of the recombinant prion protein substrate needed for the assay, providing training for laboratories wishing to adopt RT-QuIC, following up on trained personnel, certification of laboratories for diagnosis, and developing protocols for handling suspect samples.


4.     Evaluating Management Strategies across State Boundaries. Workshop participants advocated for a multistate adaptive management approach. Although scientific approaches are used to inform management decisions, science is less commonly factored into the evaluation of the impacts of management actions. Topics of interest include evaluation of how hunting and CWD regulations impacts sex and age structure of the harvest and disease dynamics (prevalence vs. spread).  Participants also identified the need for standardization of data, coordination of CWD surveillance efforts, and when possible combining data for cross-jurisdictional analysis of CWD harvest surveillance and research data to increase understanding of CWD epidemiology and effects of disease management actions.
 
5.     Enhanced Coordination, Understanding, and Communication of Social Science as it relates to CWD Research and Management (Wildlife, Agriculture, Public Health, Science Communication). Collective understanding of heterogeneous social values, motivations, and attitudes is inadequate at present to evaluate and inform disease management decision-making at local, state, and regional levels. Additionally, effective, targeted, and consistent communication strategies are critical to gain and maintain public support for necessary management interventions. A multistate effort could serve as a central scientific advisory group; increase coordination of human dimensions research; and assist federal, state and local agencies in developing effective policies and strategies to slow CWD spread as well as consistent, scientifically accurate messaging. Workshop participants identified the need to bring social scientists and communication specialists into the consortium.


All of these research themes would rely on multiple disciplines and multiple states or provinces to address critical gaps in the current understanding and management of CWD. The workshop went beyond identifying priority research themes and began to formulate plans to address some of the critical needs that can be addressed in the next year or so. Workshop participants agreed to begin laying the groundwork for a national tissue clearinghouse and to facilitate access to the substrate for RT-QuIC to promote wider adoption of this sensitive prion detection method. Additionally, participants have begun to develop the framework for evaluating management strategies across state boundaries by building support for this effort among the directors of state wildlife agencies during the recent Association of Fish and Wildlife Agencies (AFWA) meeting.  In summary, the workshop produced considerable enthusiasm and generated momentum toward achieving the identified research priorities. We think that this augurs well for the success of the multistate project we propose.


Contributions of the Participating Agricultural Experiment Stations. 


Ten agricultural experiment stations participated in our initial workshop and a further four indicated interest in future participation. The researchers associated with these stations bring a wide range expertise to address the proposed study objectives. We expect Colorado State University (co-lead), Pennsylvania State University (co-lead), Cornell University,  and University of Wisconsin – Madison to contribute strongly to Objective 1 along with Michigan State University, University of Minnesota, and University of Missouri. Objective 2 would include Texas A & M (lead), Iowa State University, Mississippi State University, and University of Tennessee. The research team for Objective 3 would encompass Cornell University (co-lead), Colorado State University (co-lead), University of Wisconsin – Madison, University of Minnesota, and Mississippi State University. Objective 4 would include University of Wisconsin – Madison (lead), Michigan State University, Cornell University, the University of Arkansas, Iowa State University, Mississippi State University, and University of Tennessee. Finally, Objective 5 would draw on the expertise of University of Minnesota (lead), Michigan State University, University of Arkansas, Iowa State University, and Cornell University. Given the breadth of relevant expertise at Michigan State University, University of Minnesota, and University of Missouri we expect that researchers from these universities will participate in all five objectives. The breadth of experiment stations engaged in multistate research on CWD through our proposed collaborative effort reflects the current need for such research to meet the challenges of this disease.


Expected Outcomes and Impacts. Research across multiple disciplines is essential to fully address the complexities of CWD and acquire the knowledge needed to limit or eliminate its spread. Research programs are emerging and maturing at multiple universities and government agencies. These are developing in parallel with little coordination. For example, within institutions of higher education around the Great Lakes region alone, four large studies in different states have been initiated within the last two years to investigate the role of movement behavior in shaping epidemiological models of CWD. Furthermore, disparate methods of surveillance for the disease (e.g., no sampling or only sampling hunter harvest) has resulted in new disease outbreaks being documented with prevalence levels that indicate the disease could have been present for many years. The proposed multistate consortium would improve the coordination of research efforts and exchange of information and materials among universities and researchers with common goals, but different backgrounds and knowledge bases. Increased collaboration would improve research quality by standardizing protocols, enabling and validating sensitive methods to measure CWD prions, permit modeling of CWD across jurisdictions leading to an improved understanding of CWD epidemiology, and avoid duplication of work at a critical time when effective solutions are needed quickly.


Progress will be tracked at the subcommittee meetings and at annual meetings for the entire multistate project. Annual multistate project meetings will include time allocated for developing objectives and routes to achieve them for the coming year. Subcommittees will be tasked with drafting proposed objectives and approaches ahead of annual multistate project meetings. Annual progress reports will represent formal evaluations of progress and result.


Potential duplication of efforts in existing committees: We found no active projects related to chronic wasting disease in the NIMSS database. There is no indication that the proposed consortium will duplicate the effort of any existing committee.

Related, Current and Previous Work

The workshop participants included representatives from many of the leading CWD research groups in North America. These groups have contributed substantially to current understanding of the mechanisms of CWD transmission, trafficking, and pathogenesis; characterization of species barriers and strains; transgenic mouse modeling of prion diseases; development of in vitro prion amplification assays to detect CWD prions in biological tissues, fluids, excreta, and environmental samples; investigation of the environmental behavior of CWD prions; investigation of the role of deer ecology and management; and development of prion disease therapeutics. The objectives outlined above represent the priorities developed by this group of researchers along with wildlife ecologists and those managing CWD at the state level. Below we outline the current status of work related to the proposed objectives.


Tissue database and repository. At present, individual laboratories maintain tissue samples from past studies and may use them as reference samples in their own work. The investment required to determining prion titers in reference samples is considerable. Sharing of reference samples between research groups is currently limited. The proposed multistate project would facilitate the provision of reference samples to the CWD prion research community.


Large-scale research facilities. Contaminated pens and paddocks have provided important insights into indirect, environmental transmission of sheep scrapie and CWD (e.g., Miller et al. 2004, Georgesson et al. 2006, Gough et al. 2019). Many of these studies were the result of so-called natural experiments. Across the country, breeding facilities, game farms, and other captive facilities have been shut down due to CWD. Questions surround the re-use of such contaminated facilities for commercial purposes because the longevity of CWD prion infectivity in such environments has not been defined and the efficacy of attempts to decontaminate such facilities is uncertain. The purchase of contaminated facilities by state agencies or others presents an opportunity to conduct coordinated research on CWD ecology at a scale relevant for management of deer populations.


Diagnostic testing for CWD. The detection limits, specificity, robustness, and speed of prion detection methods have improved dramatically (prion amplification methods) over the last decade and a half (Saá et al. 2006, Wilham et al. 2010, Haley et al. 2018, Escobar et al. 2019). Adoption of these methods outside of research settings has been limited by the need for trained personnel and for access to substrate for the amplification assays. The proposed multistate project would address both these needs.


Multistate adaptive management. Chronic wasting disease does not respect state or national boundaries. Currently, management efforts across the country are fragmented with little coordination across jurisdictions. Actions taken in one state can affect CWD disease dynamics in adjacent states. The proposed multistate project would facilitate communication among state wildlife managers and the development of regional management approaches.


Human dimensions research. As judged by publication rate, research in human dimensions of CWD management has progressed at a modest pace since 2000. As noted above, workshop participants deemed understanding of social values, motivations, and attitudes is inadequate at present to evaluate and inform disease management decision-making at multiple jurisdictional levels, and effective, targeted, and consistent communication strategies need to be developed to gain and maintain public support for necessary management interventions. Research in human dimensions of CWD management, including the link between communication approaches and acceptance of disease management responses, is needed to effectively design and implement management strategies. Stakeholder attitudes towards management interventions are expected to evolve with CWD epizootics and may differ in regions with no prior experience with the disease. Two efforts related to our proposed work on human dimensions with which we intend to connect are the National Socio-Environmental Synthesis Center (SESYNC) and concurrently proposed multi-state project led by the Center for Conservation Social Sciences of Cornell University (Bruce Lauber, PI). More detail about these efforts is provided under the methods for Objective 5.

Objectives

  1. Establish a national CWD tissue database and repository with improved access for transmission and pathogenesis research and validation of CWD prion detection assays.
  2. Develop large-scale research facilities for controlled CWD research using depopulated cervid facilities where CWD has been detected.
  3. Advance diagnostic testing for CWD with a focus on facilitating adoption of the RT-QuIC assay and improved sourcing for the recombinant prion protein substrate.
  4. Develop a multistate adaptive management approach for CWD to evaluate surveillance and management strategies and how deer harvest regulatory options impact deer disease dynamics.
  5. Evaluate heterogeneous social values, motivations, attitudes, and effective communication to inform disease management decision-making at local, state, and regional levels.

Methods

Objective 1. Establish a national CWD tissue database and repository with improved access for transmission and pathogenesis research and validation of CWD prion detection assays. To accomplish Objective 1, we will first establish a coordinating body that will define metadata standards, storage conditions, and procedures for vetting requests for materials. One of the outcomes of the workshop held in September 2019 was to take some initial steps towards the development of such a coordinating body. We envision the tissue and reagents bank to not be a single repository, but a clearinghouse to coordinate the provision of samples to researchers. The physical storage locations would be based on geographical proximity to sources of tissue, ideally in facilities that routinely perform CWD diagnostic services for states with high sample testing numbers. Samples will be stored at –80 °C, identified with a unique bar code that is linked to the metadata associated with the sample. A metadata gap analysis will be conducted prior to collecting and storing data. An oversight committee will be assembled which will be comprised of state and federal representatives, field biologists, basic scientists, and industry representatives as deemed appropriate. This committee will determine how samples are distributed and will develop a memorandum of understanding for how data, analyses, testing, and diagnostics will be used and any assignment of fees.

Objective 2. Develop large-scale research facilities for controlled CWD research using depopulated cervid facilities where CWD has been detected. We propose to establish CWD research sites in and around captive animal facilities where CWD has been detected. Facilities in several states would be suitable for this purpose, and collaboration among efforts in different states would be valuable to ensure efficient use of resources. Ideally, sites would have a history of holding CWD-positive deer on-site, and contain several paddocks (e.g., 1-acre paddocks surrounded by 8-ft high fences to limit deer movement), animal handling facilities, and pastures varying in size from a few to hundreds of acres.

The first step will be to assess the risks and benefits of using such facilities for research. The primary risk is the maintenance or amplification of CWD prions in the environment. Risks are expected to differ among sites and be determined in part by the current level of contamination in and around the potential research site. Benefits include providing research sites where management actions to reduce the spread and prevalence of the disease can be evaluated and refined. State and federal regulatory authorities will decide if such facilities will be permitted. If regulatory authorities permit the facility, scoping meetings with local landowners and officials would be held to seek support for the facility.

Assuming a facility was permitted and obtained local support, a stake-holder advisory group would be established to raise funds to purchase the facility (if necessary) and any surrounding land necessary to fulfil research objectives and ensure biosecurity. The stake-holder group would also raise funds to (1) make the facility and research pastures secure with double fencing of at least 8 feet high and (2) maintain the research facility once it is operational. Once these steps have been completed, title would be transferred to the agency, university, or non-governmental organization responsible for the research facility, personnel would be hired, and the facility would become operational. Funding for these projects would be sought from state and federal agencies, non-governmental organizations, and private sources. A research committee would be established with representatives from each of the state wildlife agencies where facilities are located, scientists with expertise in CWD research, and representatives from important stakeholder groups such as hunters, landowners, and the captive deer industry. Projects and funding would be evaluated and paired to make the best use of each research facility and available funding.

Objective 3. Advance diagnostic testing for CWD with a focus on facilitating adoption of the RT-QuIC assay and improved sourcing for the recombinant prion protein substrate. Efforts to manage CWD are hindered by the inability of commonly used methods to detect the low levels of prions that are relevant for disease transmission. The multistate project would facilitate the adoption of the highly sensitive RT-QuIC assay (Wilham et al. 2010) by academic laboratories and state and federal agencies. This would be accomplished by coordinating provision of the recombinant prion protein substrate needed for the assay, providing training for laboratories wishing to adopt RT-QuIC, following up on trained personnel, certification of laboratories for diagnosis, and developing protocols for handling suspect samples.

Objective 4. Develop a multistate adaptive management approach for CWD to evaluate surveillance and management strategies and how deer harvest regulatory options impact deer disease dynamics. One of the difficulties in managing CWD is that affected species range across jurisdictional boundaries; yet currently, communication or coordination among management agencies regarding CWD response is limited, and unified efforts to evaluate the effectiveness of the suite of management actions that agencies have applied for disease control are lacking. Objective 4 aims to fill these gaps by leveraging information maintained by state agencies to evaluate the impacts of CWD management activities on population and disease dynamics and establishing a framework to improve coordination and information exchange. This framework will serve as the basis for the development and implementation of an adaptive management strategy for controlling CWD among state and federal wildlife management agencies. Recognizing that harvest management is the main tool available for agencies to control both deer population sizes and CWD and that its application varies dramatically across state agencies, we will investigate the impacts of harvest regulations on the realized harvest within and among states. Specifically, initial work will focus on regulation-driven changes to the size and age/sex structure of the harvest. We will begin by surveying the participating states to ascertain the (1) variety of harvest regulations they have applied pre- and post-CWD invasion; (2) availability of spatial and temporal harvest information, including license sales, harvest reporting rates, success rates and harvest sex/age composition, associated with the various regulatory frameworks; (3) methods used to collect the harvest information and estimate these rates; (4) availability of ancillary data that may help this assessment (e.g., research studies); and (5) level of precision needed on key rates to permit CWD management decisions to be made. The results of the survey will help to guide the analysis and elucidate key gaps that may hinder the collation of data across agencies and a regional assessment of regulatory impacts on deer harvest. If the survey demonstrates that enough information is currently available for analysis, we will solicit this information from each participating agency. This will entail working with each agency to ensure data are standardized and interpretable. We will employ Bayesian statistical techniques to estimate the effects of various regulations on deer harvest within and between states based on this standardized dataset. In the event that the survey reveals gaps too substantial to overcome in some states, we will convene a meeting with these agencies to develop a protocol that can be applied to capture the needed information and work to implement these practices to permit the desired evaluation in the future. The next step will be to tie the above analytical results to CWD dynamics. We will employ stochastic compartmental disease models to simulate CWD burden in populations that are parameterized using information from previous research and/or published literature. These models will be simulated under a variety of transmission scenarios (i.e., varying rates of direct and indirect transmission). We will then introduce harvest regulations and associated harvest rates into the system, based on the results from above, and measure the potential effects of harvest regulations on disease processes and outcomes. This will permit us to make recommendations on the harvest regulations most likely to have the desired outcome for managing CWD. This effort will be coordinated with existing work at Michigan State University. Finally, using the results of this modeling effort we will work with participating state agencies to implement the harvest regulations that appear most effective in their CWD-affected areas. This will require monitoring of the realized impacts of these regulations on both population sizes and disease burden. This monitoring will provide key information for assessing the effectiveness of management activities and adapting future disease control efforts. Thus, the over-arching goal of this theme is to capitalize on the breadth of management responses that agencies in the Midwest and elsewhere have made after CWD introduction to measure the impact of harvest regulations, on deer harvest and ultimately CWD. This knowledge will guide CWD management in the Midwest under an adaptive management approach.

Objective 5. Evaluate heterogeneous social values, motivations, attitudes, and effective communication to inform disease management decision-making at local, state, and regional levels. A major challenge in CWD management and control is inadequate understanding and integration of social values, motivations, and attitudes into disease management decision-making and effective communication of necessary management actions that connects stakeholders. Wildlife and cervid farming regulations can increase or decrease the spread of CWD, but their effectiveness depends on buy-in by relevant stakeholders (e.g., hunters, farmers, landowners). A need remains for improved understanding of social values, motivations, and attitudes toward CWD and the interaction between the resulting behaviors and CWD management. Equally important is the need for scientific evaluation of targeted communication strategies surrounding management and policy in their effectiveness. We intend a multidisciplinary, multiagency, multistate approach to meeting these challenges through an iterative process that includes disease and management experts, social scientists, and stakeholders. We propose to pursue two key activities for this: Activity 1. Understanding stakeholder values and motivations associated with CWD management and control. We propose to establish a formal working group that would include scientists from public health, wildlife management, epidemiology, prion, and social sciences, as well as communication specialists. The overarching goal of this group would be to prioritize communication needs and develop strategies for CWD messaging across ecological contexts (areas with varying levels of CWD) in association with control, mitigation, and public health. The group would meet quarterly in the first year to (1) refine goals and objectives developed at the September 2019 workshop (Table 1), (2) identify several key stakeholders to bring into the process early, and (3) work toward funding recruitment and support for research endeavors. Key stakeholders would include hunter organizations, cervid farmer organizations, land owners, and others groups impacted by CWD. Involving stakeholders early in the process has been identified as a critical need to ensure interests and perspectives are well represented in the prioritization of communication needs, as well as to enhance audience trust in CWD messaging through stakeholder delivery of key messages. Additionally, this kind of multidisciplinary work to explore the human dimensions of CWD, aligns well with The National Socio-Environmental Synthesis Center (SESYNC), which convenes science teams to work on broad issues of national and international relevance to find solutions to complex environmental problems. Thus, we will explore opportunities with SESYNC to leverage its support and capacity to meet our team’s objectives, particularly in relation to Aim 1 (Table 1), where the “Propose a Priority” program (https://www.sesync.org/opportunities/propose-a-pursuit) may be an opportunity to assemble human dimensions data across states and regions to summarize and conduct an analysis of human behaviors/responses to CWD under different ecological contexts (e.g., history in a region, prevalence level, management actions). These objectives align with concurrent work led by the Center for Conservation Social Sciences of Cornell University (Bruce Lauber, PI). Finally, we would facilitate the identification of research gaps in CWD human dimensions research and inform the design and implementation of new human dimensions research. Activity 2: Develop, implement, and measure the effectiveness of targeted communication strategies on CWD management and control for different audiences. The newly formed Human Dimensions working group would create a consensus document of current CWD best practices for management and control, leveraging existing efforts such as the American Fish and Wildlife Association’s Best Practices for CWD management. This document would form the basis of scientifically-informed recommendations prioritized for dissemination to different stakeholder groups. The working group, which will include communication specialists, will use results from Activity 1 to develop strategies for communicating the science on CWD that meet the needs and prioritize the values and motivations of each stakeholder group (Figure 1). This endeavor would include the development of materials on recommended CWD management actions that can be shared with policymakers at various levels. Simultaneously, the working group will design and implement a plan for measuring the impact of varying communication strategies across locations (states, regions) in garnering stakeholder trust and effecting changes in behavior and attitudes. This might include a variety of survey methods, distributed alongside the communication mechanism, as well as structured and unstructured interviews of informants from the targeted stakeholder groups. This may include metrics that reflect changes in stakeholder behavior, such as annual trends in hunting license purchases, frequency of CWD test submissions across varying hunting zones, adoption of biosecurity and CWD surveillance regulations on farms, and trends in the integration of CWD management actions and funding in policies and bills. These results will be used to refine communication strategies, including message context and delivery while maintaining the science-informed content for the intended audience (Figure 1).

Measurement of Progress and Results

Outputs

  • Objective 1. Establish a national CWD tissue database and repository with improved access for transmission and pathogenesis research and validation of CWD prion detection assays. Comments: The significance of the outputs for Objective 1 is multifold. First, a repository of CWD field isolates from a wide range of geographic locations in North America will allow, for the first time, the means to begin to assess the distribution and frequency of CWD strains in North America. Since prion strains can differ in pathogenicity and host range, these are essential data for the determination for risk of interspecies prion transmission to humans and to domestic livestock and wildlife. Second, this repository can provide uniform standardized CWD-infected and uninfected sources of tissue for diagnostic assay development, mitigation testing, and for basic research purposes. Finally, the implementation of the repository will facilitate cooperation among the various state agencies that could lead to new collaborative efforts.
  • Objective 2. Develop large-scale research facilities for controlled CWD research using depopulated cervid facilities where CWD has been detected. Comments: This first output of this objective will include identifying potential facilities, evaluating them for use in CWD research, and working with governmental regulators and local stakeholders on permitting and acceptance of a research objective for these facilities. The second output would be to obtain funding to purchase, modify to meet research and biosecurity requirements, and manage each research facility. The third output would be research projects conceived, funded, conducted, and published. The fourth output will be graduates students trained in CWD research techniques and the ecology and management of the disease.
  • Objective 3. Advance diagnostic testing for CWD with a focus on facilitating adoption of the RT-QuIC assay and improved sourcing for the recombinant prion protein substrate. Comments: Outputs of this objective include the training of personnel in producing substrate and in conducting the RT-QuIC assay, facilitating access to substrate for laboratories that have not yet developed the capability to generate substrate, certifying laboratories, and developing protocols for dealing with suspect samples. We anticipate training representatives from a number of groups during the first year as well as developing protocols for dealing with suspect samples of specific types.
  • Objective 4. Develop a multistate adaptive management approach for CWD to evaluate surveillance and management strategies and how deer harvest regulatory options impact deer disease dynamics. Comments: First, we will assemble a standardized dataset related to deer harvest rates and regulations that will encompass information from wildlife management agencies across the Midwest. Secondly, we will develop mathematical models to be used to forecast the most efficacious regulations for CWD management. These models can also be used to answer additional questions related to deer and CWD management and will be made publicly available for that purpose. This theme will also create platform for enhanced communication and coordination among wildlife management agencies. Lastly, we will build and an implement an adaptive management strategy for CWD and deer management that is multijurisdictional.
  • Objective 5. Evaluate heterogeneous social values, motivations, attitudes, and effective communication to inform disease management decision-making at local, state, and regional levels. Comments: Outputs early in the project would include the formation of a scientific team to design new, multi-state studies on values and motivations across stakeholder groups impacted by CWD and the development of strategies for communicating the science on CWD that meet the needs and prioritize the values and motivations of stakeholder groups. Plans would be design and implemented to measure the impact of varying communication strategies across locations. Ultimately, this objective will produce knowledge about best practices in designing communication strategies related to CWD.

Outcomes or Projected Impacts

  • Objective 1. Establish a national CWD tissue database and repository with improved access for transmission and pathogenesis research and validation of CWD prion detection assays. Outcomes from establishing a tissue repository or bank and an associated database will be multifold. Data from this effort will include a survey of CWD strains over a wide geographical region. Additionally, polymorphisms of the host prion protein can be determined. These data will be useful in combination with environmental and weather patterns in determining factors that may influence the distribution of prion strains and how changes in long-term weather patterns may alter this distribution. These data may be used to better predict the populations of cervids and the environments that CWD may more likely spread to. This information can be used to focus surveillance resources. Strain distribution, in conjunction with studies on how strains of CWD affect zoonotic potential, can be used to address areas where zoonotic potential of CWD is the highest to focus mitigation resources. Monitoring the strain prevalence over time will provide important information regarding CWD strain dynamics and will enable identification of novel emerging strains that may exhibit altered pathogenicity or zoonotic potential compared to currently circulating CWD strains.
  • Objective 2. Develop large-scale research facilities for controlled CWD research using depopulated cervid facilities where CWD has been detected. Achievement of this objective will provide CWD scientists with facilities to address key aspects of CWD management and ecology that are difficult to study with current resources. Graduate students interested in studying CWD transmission, persistence, and management will have facilities to learn about these crucial aspects of the disease. State wildlife agencies, private wildlife biologists, and land owners will have knowledge they can use to manage deer in the face of CWD and thereby reduce the impacts of the disease on deer populations and wildlife conservation.
  • Objective 3. Advance diagnostic testing for CWD with a focus on facilitating adoption of the RT-QuIC assay and improved sourcing for the recombinant prion protein substrate. Successful achievement of this objective will result in the certification of laboratories across the country for use of RT-QuIC for diagnostic purposes. State and federal agencies will be able to confidently use RT-QuIC to sensitively measure CWD prions in a variety of sample types.
  • Objective 4. Develop a multistate adaptive management approach for CWD to evaluate surveillance and management strategies and how deer harvest regulatory options impact deer disease dynamics. The major outcome of this theme will be an improved ability to manage CWD in the Midwest and elsewhere in North America. This will be accomplished by providing managers with critical information on the use of harvest as a management tool for this disease, fostering multijurisdictional collaboration, and establishing an adaptive management strategy that will lead to regional disease response efforts.
  • Objective 5. Evaluate heterogeneous social values, motivations, attitudes, and effective communication to inform disease management decision-making at local, state, and regional levels. Achievement of this objective will lead to sustained and broad public/stakeholder support for research and management (prevention, contamination, mitigation) of CWD that is demonstrated through behavioral changes that are responsive to management recommendations and regulations, enhanced funding support, and increased collaborations across stakeholder groups. Further outcomes include enhanced trust by the public and key stakeholder groups in management agency decisions and recommendations, implementation of science-based actions and policy rule-making by governing bodies, and effective CWD control and mitigation as evidenced by lack of new captive facility outbreaks or spread to new populations.

Milestones

(2020):Formalize administrative structure (including subcommittee membership), initiate research, and identify additional state organizations and researchers willing to actively contribute to each of the 5 objectives. Prepare and submit first group research proposal. Proposals will be developed in all years and research will be based on funding success. Additional milestones in the first project year include • Development of a policy on tissue distribution and a data sharing agreement with state organizations who are willing to participate in this program. Identify the sites of physical storage of CWD samples. Identify procedures for shipping and begin metadata recording of samples into a database. • Identify key personnel in cooperating states and assess available large-scale facilities. Seek regulatory approval and local stakeholder acceptance of facilities. • Develop protocols for dealing with suspect samples of specific types being analyzed by RT-QuIC.

(2021):Prepare presentations and publications based on previous years' activities and research. Additional milestones in the second project year include • Certify first set of laboratories for using RT-QuIC for diagnostic purposes. • Secure funding to acquire and operate permitted large-scale facilities.

(2022):Prepare presentations and publications based on previous years' activities and research. Additional milestones in the third project year include • Secure funding to acquire and operate permitted large-scale facilities. • Completed analysis of deer harvest regulation packages on CWD growth and spread.

(2023):Prepare presentations and publications based on previous years' activities and research. Additional milestones in the fourth project year include • Initiate operations and start CWD research at the large-scale facilities. • Develop and then work with interested states to implement and test an adaptive management framework for deer harvest frameworks with the explicit purpose of controlling spread and growth of CWD

(2024):Prepare presentations and publications based on previous years' activities and research. Additional milestones in the fifth project year include. • Submit final report for the multistate project and proposal for second 5-year period of the project provided sufficient support exists.

Projected Participation

View Appendix E: Participation

Outreach Plan

Our project will generate multiple peer-reviewed publications in disciplinary and impactful journals. We will also produce shorter communications for the public in professional magazines (e.g., The Wildlife Professional), on partnering agency websites, and through respective land-grant university extension communications. Research presentations will be targeted to regional, national, and international conferences. Participants with an outreach and extension role will further disseminate progress and results to agency wildlife managers and the public. Given the national importance of CWD, we anticipate project participants communicating results to state and federal agencies and legislatures.

Organization/Governance

Membership in the proposed multistate project will be open to SAES scientists, other public and private sector scientists, extension professionals, administrative advisors, CSREES representatives, and others who are in a position to contribute to the proposed activities. Voting members will consist of one representative from each member SAES. Voting membership may be extended to other members not affiliated with a SAES upon a majority vote of the voting members. In addition to conducting the agreed-upon research collaboration, project members are responsible for reporting progress, contributing to the ongoing progress of project activities, and communicating their accomplishments to the committee members and their respective employing institutions.


All voting members of the committee are eligible for office, regardless of sponsoring agency affiliation. The executive committee consists of the officers:
Past chair: The past chair will prepare the annual report for the year in which s/he served as chair. The past chair will assist the chair to ensure a smooth transition. The past chair will serve as chair in the absence of both the elected chair and vice-chair.


Chair: In consultation with the administrative adviser, notifies the committee members of the time and place of meetings, prepares the agenda, presides at meetings of the committee and the executive committee. The chair is responsible for preparing or supervising the preparation of the annual report of the project. The chair will serve a one-year term.


Vice-chair: Succeeds the chair and is expected to carry out duties assigned by the chair. The chair-elect serves as the chair in the absence of the elected chair. The chair-elect will serve a one-year term and will succeed to the chair the following year.


Secretary: records the minutes and performs other duties assigned to him/r by the committee or the administrative advisor. The secretary shall prepare and e-mail the minutes of any official meeting to committee members within 4 weeks after the end of the meeting. The secretary shall be responsible for assisting the chair to prepare official communications to the administrative advisor, NIMSS, and other external parties. The secretary will serve a one-year term and succeed to the vice-chair the following year.


Subcommittees will be named by the chair as needed for specific assignments. This may include subcommittees to develop procedures, manuals, and phases of the regional project; to review work assignments; to develop research methods; and to prepare publications. One of the outcomes of the September 2019 workshop was the initial formation of subcommittees associated with each of the project objectives.


 

Literature Cited

Almberg, E.S., P.C. Cross, C.J. Johnson, D.M. Heisey, B.J. Richards. 2011. Modeling routes of chronic wasting disease transmission: environmental prion persistence promotes deer population decline and extinction. PLoS One 6:e19896.


Angers, R.C., S.R. Browning, T.S. Seward, C.J. Sigurdson, M.W. Miller, E.A. Hoover, G.C. Telling. 2006. Prions in skeletal muscles of deer with chronic wasting disease. Science 311:1117


Baeten, L.A., B.E. Powers, J.E. Jewell, T.R. Spraker, MW. 2007. A natural case of chronic wasting disease in a free-ranging moose (Alces alces shirasi). J Wildlife Manage 43:309-314.


Benestad, S. L., G. B. Mitchell, M. Simmons, B. Ytrehus, T. Vikøren. 2016. First case of chronic wasting disease in Europe in a Norwegian free-ranging reindeer. Vet. Res. 47:1-7.


Bishop, R.C. 2004. The economic impacts of chronic wasting disease (CWD) in Wisconsin. Human Dim Wildl 9:181-192.


Brown, P., D.C. Gajdusek. 1991. Survival Of scrapie virus after 3 years internment. Lancet 337:269-270.


Centers for Disease Control and Prevention. 2017. Chronic wasting disease (CWD). Retrieved from https://www.cdc.gov/prions/cwd/index.html.


Chesney, A. R., C. J. Booth, C. B. Lietz, L. Li, J. A. Pedersen. 2016. Peroxymonosulfate rapidly inactivates the disease-associated prion protein. Environ Sci Technol 50:7095-7105.


Colby, D.W. and S.B. Prusiner. 2011. Prions. Cold Spring Harb Perspect Biol 3:a006833.


Czub, S., W. Schulz-Schaeffer, C. Stahl-Hennig, M. Beekes, H. Schaetzl, D. Motzkus. 2017. First evidence of intracranial and peroral transmission of chronic wasting disease (CWD) into Cynomolgus macaques: a work in progress. Presentation at the PRION 2017 Conference, Edenborough, Scotland.


Davenport, K. A., J. R. Christiansen, J. Bian, M. Young, J. Gallegos, S. Kim, A. Balachandran, C. K. Mathiason, E. A. Hoover, G. C. Telling. 2018. Comparative analysis of prions in nervous and lymphoid tissues of chronic wasting disease-infected cervids. J Gen Virol 99:753-758.


Denkers, N. D., D. M. Henderson, C. K. Mathiason, E. A. Hoover. 2016. Enhanced prion detection in biological samples by magnetic particle extraction and real-time quaking-induced conversion. J. Gen. Virol. 97:2023-2029.


Escobar, L. E., S. Pritzkow, S. N. Winter, D. A. Grear, M. S. Kirchgessner, E. Dominguez-Villegas, G. Machado, A. T. Peterson, C. Soto, C. 2019. The ecology of chronic wasting disease in wildlife. Biol. Rev. (in press)


Edmunds, D.R., M.J. Kauffman, B.A. Schumaker, F.G. Lindzey, W.E. Cook, T.J. Kreeger, R.G. Grogan, T.E. Cornish. 2016. Chronic wasting disease drives population decline of white-tailed deer. PLoS One 11:e0161127.


Georgsson, G., S. Sigurdarson, P. Brown, P. 2006. Infectious agent of sheep scrapie may persist in the environment for at least 16 years. J Gen Virol 87:3737-3740


Goni, F., C.K. Mathiason, L. Yim, K. Wong, J. Hayes-Klug, A. Nalls, D. Peyser, V. Estevez, N. Denkers, J. Xu, D.A. Osborn, K.V. Miller, R.J. Warren, D.R. Brown, J.A. Chabalgoity, E.A. Hoover, T. Wisniewski. 2015. Mucosal immunization with an attenuated Salmonella vaccine partially protects white-tailed deer from chronic wasting disease. Vaccine 33:726-733.


Gough, K. C., C. A. Baker, S. Hawkins, H. Simmons, T. Konold, B. C. Maddison. 2019. Rapid recontamination of a farm building occurs after attempted prion removal. Vet. Rec. 184:97.


Gross, J.E. and M.W. Miller. 2001. Chronic wasting disease in mule deer: disease dynamics and control. J Wildl Manag 65:205-215.


Haley, N. J., J. A. Richt, K. A. Davenport, D. M. Henderson, E. A. Hoover, M. Manca, B. Caughey, D. Marthaler, J. Bartz, S. Gilch. 2018. Design, implementation, and interpretation of amplification studies for prion detection. Prion 12:73-82.


Haley, N.J. and J.A. Richt. 2017. Chronic wasting disease: evolution of diagnostic testing for a naturally occurring prion disease. Pathogens 6:35.


Haley, N.J., D.M. Seelig, M.D. Zabel, G.C. Telling, E.A. Hoover. 2009. Detection of CWD prions in urine and saliva of deer by transgenic mouse bioassay. PLoS One 4:e4848.


Haley, N. J., C. K. Mathiason, S. Carver, G. C. Telling, M. D. Zabel, E. A. Hoover. 2012. Sensitivity of protein misfolding cyclic amplification versus immunohistochemistry in ante-mortem detection of chronic wasting disease. J Gen Virol 93:1141-1150.


Henderson, D. M., K. A. Davenport, N. J. Haley, N. D. Denkers, C. K. Mathiason, E. A. Hoover. 2015a. Quantitative assessment of prion infectivity in tissues and body fluids by real-time quaking-induced conversion. J Gen Virol 96: 210-219.


Henderson, D.M., N.D. Denkers, C.E. Hoover, N. Garbino, C.K. Mathiason, E.A. Hoover. 2015b. Longitudinal detection of prion shedding in saliva and urine by chronic wasting disease-infected deer by real-time quaking-induced conversion. J Virol 89:9338-9347.


Henderson, D. M., J. M. Tennant, N. J. Haley, N. D. Denkers, C. K. Mathiason, E. A. Hoover. 2017. Detection of chronic wasting disease prion seeding activity in deer and elk feces by real-time quaking-induced conversion. J Gen Virol 98:1953-1962.


Johnson, C., J. Johnson, J.P. Vanderloo, D. Keane, J.M. Aiken, D. McKenzie. 2006. Prion protein polymorphisms in white-tailed deer influence susceptibility to chronic wasting disease. J Gen Virol 87:2109-2114.


Manjerovic, M.B., M.L. Green, N. Mateus-Pinilla, J. Novakofski. 2014. The importance of localized culling in stabilizing chronic wasting disease prevalence in white-tailed deer populations. Prev Vet Med 113:139-145.


Marsh RF, Kincaid AE, Bessen RA, Bartz JC (2005) Interspecies transmission of chronic wasting disease prions to squirrel monkeys (Saimiri sciureus). J Virol 79:13794-13796


Mathiason, C.K., J.G. Powers, S.J. Dahmes, D.A. Osborn, K.V. Miller, R.J. Warren, G.L. Mason, S.A. Hays, J. Hayes-Klug, D.M. Seelig, M.A. Wild, L.L. Wolfe, T.R. Spraker, M.W. Miller, C.J. Sigurdson, G.C. Telling, E.A. Hoover. 2006. Infectious prions in the saliva and blood of deer with chronic wasting disease. Science 314:133-136.


Miller, M.W., E.S. Williams, N.T. Hobbs, L.L. Wolfe. 2004. Environmental sources of prion transmission in mule deer. Emerg Infect Dis 10:1003-1006.


Pritzkow, S., R. Morales, F. Moda, U. Khan, G. C. Telling, E. A. Hoover, C. Soto. 2015. Grass plants bind, retain, uptake, and transport infectious prions. Cell Rep 11:1168-1175.


Prusiner, S. B. 1982. Novel proteinaceous infectious particles cause scrapie. Science 216:136-144.


Prusiner S.B. 1998. Prions. Proc Natl Acad Sci USA 95:13363–13383


Plummer, I. H., C. J. Johnson, A. R. Chesney, J. A. Pedersen, M. D. Samuel. 2018. Mineral licks as environmental reservoirs for chronic wasting disease prions. PLoS ONE 13:e0196745.


Race B, Meade-White K, Race R, Chesebro B (2009) Prion infectivity in fat of deer with chronic wasting disease. J. Virol. 83:9608-9610.


Race, B., K. Williams, C. D. Orrú, A. G. Hughson, L. Lubke, B. Chesebro. 2018. Lack of Transmission of chronic wasting disease to cynomolgus macaques. J Virol 92:1-18.


Saá, P., J. Castilla, C. Soto. 2006. Ultra-efficient replication of infectious prions by automated protein misfolding amplification. J. Biol. Chem. 281:35245-35252.


Safar, J.G., P. Lessard, G. Tamguney, Y. Freyman, C. Deering, F. Letessier, S.J. Dearmond, S.B. Prusiner. 2008. Transmission and detection of prions in feces. J Infect Dis 198:81-89.


Seidel, B., A. Thomzig, A. Buschmann, M. H. Groschup, R. Peters, M. Beekes, K. Terytze. 2007. Scrapie agent (Strain 263K) can transmit disease via the oral route after persistence in soil over years. PLoS ONE 2:e435


Seidl, A.F., and S.R. Koontz. 2004. Potential economic impacts of chronic wasting disease in Colorado. Human Dim Wildl 9:241-245.


Sigurdson, C. J., C. Barillas-Mury, M. W. Miller, B. Oesch, L. J. M. Van Keulen, J. P. M. Langeveld, E. A. Hoover. 2002. PrPCWD lymphoid cell targets in early and advanced chronic wasting disease of mule deer. J Gen Virol 83: 2617-2628.


Smith, C.B., C.J. Booth, J.A. Pedersen. 2011. Fate of prions in soil: A review. J Env Qual 40:449-461.


Spraker, T.R., T. Gidlewski, J.G. Powers, T. Nichols, A. Balachandran et al. 2015. Progressive accumulation of the abnormal conformer of the prion protein and spongiform encephalopathy in the obex of non-symptomatic and symptomatic Rocky Mountain elk (Cervus elaphus nelsoni) with chronic wasting disease. J Vet Diagn Invest 27:431–441.


Tamgüney, G., M.W. Miller, L.L. Wolfe, T.M. Sirochman, D.V. Glidden, C. Palmer, A. Lemus, S.J. DeArmond, S.B. Prusiner. 2009. Asymptomatic deer excrete infectious prions in faeces. Nature 461:529-532


Taylor, D. M. 1999. Inactivation of prions by physical and chemical means. J Hosp Infect 43(Suppl):S69−76


Wilham, J. M., C. D. Orrú, R. A. Bessen, R. Atarashi, K. Sano, B. Race, K. D. Meade-White, L. M. Taubner, A. Timmes, B. Caughey. 2010. Rapid end-point quantitation of prion seeding activity with sensitivity comparable to bioassays. PLoS Pathog. 6:e1001217.


Williams, E., 2005. Chronic wasting disease. Vet Pathol 42:530-549.


Williams, D.M., A.C. Dechen Quinn, W.F. Porter. 2014. Informing disease models with temporal and spatial contact structure among GPS-collared individuals in wild populations. PLOS One 9:e84368.


Williams, K., A. G. Hughson, B. Chesebro, B. Race. 2019. Inactivation of chronic wasting disease prions using sodium hypochlorite. PLOS One 14:e0223659.


Xu, S., T. Reuter, B.H. Gilroyed, S. Dudas, C. Graham, N.F. Neumann, A. Balachandran, S. Czub, M. Belosevic, J.J. Leonard. 2013. Biodegradation of specified risk material and fate of scrapie prions in compost. J Env Sci Health, Pt A 48:26-36.

Attachments

Land Grant Participating States/Institutions

AR, CO, IA, MI, MN, MO, MS, NY, SD, TN

Non Land Grant Participating States/Institutions

Arkansas Game and Fish Commission, Case Western Reserve University, Colorado State University, Creighton University, Idaho Fish and Game, Iowa Department of Natural Resources, Johns Hopkins University, Michigan Department of Natural Resources, Minnesota Department of Natural Resources, State of Minnesota, Tennessee Wildlife Resources Agency , Texas A&M University - Kingsville, The University of Texas Health Science Center at Houston, University of Alberta, University of Calgary, University of Georgia, University of Minnesota, University of Pennslyvania, University of Wisconsin-Madison, USDA Forest Service, USDA Wildlife Services, USDA-APHIS, USDA-ARS/CO, USDA-ARS/Iowa, USDA-ARS/Washington, USDA/APHIS Veterinary Services, USDA/APHIS/WS/National Wildlife Research Center, USGS, USGS National Wildlife Health Center, Western Association of Fish and Wildlife Agencies, Wisconsin Department of Natural Resources
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