NC1209: North American interdisciplinary chronic wasting disease research consortium
(Multistate Research Project)
Status: Active
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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.