MODELING HOST BEHAVIOR AND ENVIRONMENTAL TRANSMISSION OF CHRONIC WASTING DISEASE

We propose to develop broadly applicable mechanistic models uniting direct and environmental transmission processes across scales. We will use a novel application of homogenization techniques to mechanistic models, allowing us to analytically integrate the impact of small-scale variability on large-scale population processes. Consequently, our proposed approach is well-suited to modeling the multi-scale data streams and underlying drivers governing disease dynamics and will provide critical advances beyond standard compartmental modeling approaches. By integrating processes including landscape structure, host movement ecology, pathogen distribution, and transmission modes in a tractable, homogenized model framework, we will link underlying transmission mechanisms with emergent disease processes (e.g., spatial spread, observed prevalence). Further, we will embed this mathematical model within a statistical framework that allows estimation of uncertainty around model forecasts, rigorous model evaluation, and testing of disease ecological hypotheses using model competition. Our approach will elucidate the relative importance of transmission pathways and have the capacity to predict and evaluate system responses to population management and landscape disturbance.To develop and demonstrate this analytic framework, we will focus on a critically important host-pathogen system with both direct and environmental transmission: chronic wasting disease (CWD) in white-tailed deer (Odocoileus virginianus). CWD is an invariably fatal neurologic disease of cervids that is increasing in endemic areas and spreading broadly. It currently affects cervids in 26 US states, 3 Canadian provinces, and Norway, Finland, Sweden and South Korea. Most state agency activities related to conservation of game and non-game species are funded by deer hunter license sales. This makes CWD a major management concern for wildlife agencies, given its potential to negatively affect deer populations and/or hunter participation, and managers need tools to guide these management efforts.The etiological agent of CWD, a mis-folded protein known as a prion, can be transmitted directly between hosts or indirectly from prion-contaminated environments (i.e., environmental reservoirs). Heterogeneities in deer habitat, behavior, and movement mediate direct transmission, but those same heterogeneities also affect the understudied--yet increasingly important--environmental transmission. Prions enter the environment from carcasses of infected animals and shedding by infected cervids via secretions and excreta during a long incubation period. Shedding is likely to accumulate prions at localized attractant sites such as mineral licks or deer scent marking sites where deer perform behaviors conducive to prion shedding, including defecating, urinating, or leaving scent-marking secretions on vegetation and soil. Scent marking sites are frequented and marked by multiple individuals, particularly in the breeding season, and exemplify how social behaviors conducive to prion deposition may be clustered in space and/or time. Post-deposition, prions are stable for long periods of time in the environment, can be taken up by plants, and bind with soil, which can increase infectiousness. Thus, multi-scale factors, such as prion kinetics in the environment, heterogeneous habitats and dynamic deer behaviors and movements, shape multiple routes of direct transmission, environmental contamination and exposure for deer in affected regions. This makes the CWD-deer system well-suited to our integrative, mechanistic modeling approach, and allows us to leverage on-going research and include novel data streams in our analytical framework. Since the drivers of CWD disease dynamics (e.g., host social behavior and heterogeneous disease risk on landscapes) are common among host-pathogen systems, our framework will be broadly applicable across human and animal systems.Our interdisciplinary team includes disease ecologists, mathematicians, statisticians, wildlife biologists, prion biologists, soil chemists and environmental scientists, who, in developing our analytical framework, will address these research questions (RQ):RQ1: How can mechanistic disease models be expanded to incorporate multi-scale data on landscape variability, spatiotemporal structure of host-pathogen contacts, as well as behavioral drivers relating habitat preference, and interactions with environmental reservoirs? Our deterministic model scaffold will synthesize diverse, unexplored spatiotemporal influences on disease transmission. Homogenization applied to candidate models will increase the capacity to incorporate detailed multi-scale data, vastly improve computational efficiency, and thereby facilitate a conceptual framework incorporating large, complex data on prevalence and individual hosts, as well as environmental and pathogen covariates.RQ2: How does the type of environmental reservoir, and the persistence, concentration and transport of infectious agents within reservoirs, affect infection risk in a heterogeneous landscape? Our development and application of new diagnostic methods will elucidate the retention, transport, extent (i.e., spatial footprint), and infection potential of prions in heterogeneous soil and plant environments.RQ3: How do heterogeneities in landscape and host behavior shape transmission risk at environmental pathogen reservoirs? Using deer movement and behavioral data we will determine landscape structuring of host habitat preference and aggregation sites, potential environmental prion reservoirs, and deer preference for and risk behavior at these and other host aggregation sites.RQ4: What is the relative importance of direct vs. environmental transmission in pathogen dynamics? Our hierarchical uncertainty approach, facilitated by homogenization of the mechanistic process models, will evaluate hypotheses regarding direct/environmental CWD transmission. The resulting predicted and forecasted prevalence surfaces, with measures of uncertainty, will guide future CWD prevention and control efforts.