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Spatio-temporal ecological models via physics-informed neural networks for studying chronic wasting disease

To mitigate the negative effects of emerging wildlife diseases in biodiversity and public health it is critical to accurately forecast pathogen dissemination while incorporating relevant spatio-temporal covariates. Forecasting spatio-temporal processes can often be improved by incorporating scientific knowledge about the dynamics of the process using physical models. Ecological diffusion equations are often used to model epidemiological processes of wildlife diseases where environmental factors play a role in disease spread. Physics-informed neural networks (PINN) are deep learning algorithms that constrain neural network predictions based on physical laws and therefore are powerful forecasting models useful even in cases of limited and imperfect training data. In this paper, we develop a novel ecological modeling tool using PINNs, which fits a feedforward neural network and simultaneously performs parameter identification in a partial differential equation (PDE) with varying coefficients. We demonstrate the applicability of our model by comparing it with the commonly used Bayesian stochastic partial differential equation method and traditional machine learning approaches, showing that our proposed model exhibits superior prediction and forecasting performance when modeling chronic wasting disease in deer in Wisconsin. Furthermore, our model provides the opportunity to obtain scientific insights into spatiotemporal covariates affecting spread and growth of diseases. This work contributes to future machine learning and statistical methodology development by studying spatio-temporal processes enhanced by prior physical knowledge.

Spatial Statistics

The ecology of chronic wasting disease in wildlife

Prions are misfolded infectious proteins responsible for a group of fatal neurodegenerative diseases termed transmissible spongiform encephalopathy or prion diseases. Chronic Wasting Disease (CWD) is the prion disease with the highest spillover potential, affecting at least seven Cervidae (deer) species. The zoonotic potential of CWD is inconclusive and cannot be ruled out. A risk of infection for other domestic and wildlife species is also plausible. Here, we review the current status of the knowledge with respect to CWD ecology in wildlife. Our current understanding of the geographic distribution of CWD lacks spatial and temporal detail, does not consider the biogeography of infectious diseases, and is largely biased by sampling based on hunters' cooperation and funding available for each region. Limitations of the methods used for data collection suggest that the extent and prevalence of CWD in wildlife is underestimated. If the zoonotic potential of CWD is confirmed in the short term, as suggested by recent results obtained in experimental animal models, there will be limited accurate epidemiological data to inform public health. Research gaps in CWD prion ecology include the need to identify specific biological characteristics of potential CWD reservoir species that better explain susceptibility to spillover, landscape and climate configurations that are suitable for CWD transmission, and the magnitude of sampling bias in our current understanding of CWD distribution and risk. Addressing these research gaps will help anticipate novel areas and species where CWD spillover is expected, which will inform control strategies. From an ecological perspective, control strategies could include assessing restoration of natural predators of CWD reservoirs, ultrasensitive CWD detection in biotic and abiotic reservoirs, and deer density and landscape modification to reduce CWD spread and prevalence.

Biological Reviews

Genomics reveals historic and contemporary transmission dynamics of a bacterial disease among wildlife and livestock

Whole-genome sequencing has provided fundamental insights into infectious disease epidemiology, but has rarely been used for examining transmission dynamics of a bacterial pathogen in wildlife. In the Greater Yellowstone Ecosystem (GYE), outbreaks of brucellosis have increased in cattle along with rising seroprevalence in elk. Here we use a genomic approach to examine Brucella abortus evolution, cross-species transmission and spatial spread in the GYE. We find that brucellosis was introduced into wildlife in this region at least five times. The diffusion rate varies among Brucella lineages (B3 to 8 km per year) and over time. We also estimate 12 host transitions from bison to elk, and 5 from elk to bison. Our results support the notion that free-ranging elk are currently a self-sustaining brucellosis reservoir and the source of livestock infections, and that control measures in bison are unlikely to affect the dynamics of unrelated strains circulating in nearby elk populations.

Nature Communications

Management of diseases in free-ranging wildlife populations

Diseases are increasingly threatening the conservation of wildlife species. Spillover of pathogens into humans and domestic animals may negatively impact public health and the economy, requiring increased proactive management actions. The North American Wildlife Management Model provides the philosophical basis for managing wildlife and underpins all management options. Diseases in wildlife populations may be managed by manipulation of the environment, manipulation of the host, manipulation of the agent, and modification of human behavior. Important considerations include setting management goals, and metrics to assess success. Future strategies include using systems and One Health approaches to develop interventions that optimize outcomes for humans, animals, and the environment.

Book chapter

Chronic wasting disease (CWD) knowledge, risk perception, and management acceptance are influenced by media engagement and trust among deer hunters in Massachusetts

Prior to wildlife disease emergence, public outreach campaigns can improve disease-related knowledge and increase the likelihood that stakeholders accept potential management actions. One wildlife disease of particular interest is chronic wasting disease (CWD), which is spreading across the United States but has not been detected in Massachusetts. We conducted a survey of deer hunters ( n = 7,419) in Massachusetts to: (1) explore media channel usage and source trust, and (2) assess the relationship among CWD knowledge, risk perception, management acceptability, and state wildlife agency trust. We found that channel usage and source trust varied by socio-demographic factors. We also found that engagement with popular channels and trust in accurate sources were positively correlated with CWD knowledge. CWD risk perception mediated the relationship between knowledge and management acceptance, and trust was positively associated with management acceptance. Collectively, our results indicate a mixed-media campaign by state wildlife agencies could improve CWD management acceptance.

Massachusetts

Joint spatial modeling bridges the gap between disparate disease surveillance and population monitoring efforts informing conservation of at-risk bat species

White-Nose Syndrome (WNS) is a wildlife disease that has decimated hibernating bats since its introduction in North America in 2006. As the disease spreads westward, assessing the potentially differential impact of the disease on western bat species is an urgent conservation need. The statistical challenge is that the disease surveillance and species response monitoring data are not co-located, available at different spatial resolutions, non-Gaussian, and subject to observation error requiring a novel extension to spatially misaligned regression models for analysis. Previous work motivated by epidemiology applications has proposed two-step approaches that overcome the spatial misalignment while intentionally preventing the human health outcome from informing estimation of exposure. In our application, the impacted animals contribute to spreading the fungus that causes WNS, motivating development of a joint framework that exploits the known biological relationship. We introduce a Bayesian, joint spatial modeling framework that provides inferences about the impact of WNS on measures of relative bat activity and accounts for the uncertainty in estimation of WNS presence at non-surveyed locations. Our simulations demonstrate that the joint model produced more precise estimates of disease occurrence and unbiased estimates of the association between disease presence and the count response relative to competing two-step approaches. Our statistical framework provides a solution that leverages disparate monitoring activities and informs species conservation across large landscapes. Stan code and documentation are provided to facilitate access and adaptation for other wildlife disease applications.

Journal of Agricultural, Biological and Environmen

Space matters: Host spatial structure and the dynamics of plague transmission

The development of models to elucidate the transmission pathways and dynamics of wildlife diseases remains challenging. Sylvatic plague, caused by the bacterium Yersinia pestis ( Yp ), is an infectious zoonotic disease that primarily affects wild rodents, including prairie dogs ( Cynomys spp.) in North America. Proposed transmission pathways for Yp include flea bites, direct contacts between hosts, and environmental reservoirs (e.g. soil, carcasses). We developed a spatially explicit, agent-based model of Yp transmission to explore the effects of alternative transmission pathways, different disease initiation mechanisms (host or fleas), parameter uncertainty, and spatial structure of hosts. A particularly novel aspect of our model was the integration of ecological models with traditional disease models. Specifically, we used estimates from spatial capture-recapture models to generate data-driven spatial distributions, densities, and contact rates to capture the spatial structure of prairie dogs. We simulated ~9 million scenarios across a wide range of parameter values and conducted sensitivity analyses to determine the most influential parameters on the number of flea-days (sum of the mean number of fleas on hosts each day of the simulation), number of newly infected hosts per day, the time to depopulation (<20 prairie dogs remaining), and the proportion of the prairie dog population remaining at the end of the simulation (after 150 days). When including spatial structure, we found the probability of transmission via environmental sources of Yp (i.e. carcasses) had the greatest influence on model results when Yp infection was initiated in prairie dog hosts, rather than in fleas. Conversely, the mechanism of transmission by fleas to prairie dogs had the greatest influence on model results when Yp infection was initiated in fleas (i.e. via introduction by carnivores, a migrant prairie dog, or other mammalian host). Uncertainty in parameter estimates, particularly those related to the transmission pathways of Yp, continue to hamper efforts to realistically model plague dynamics in wild rodents. Our results elucidate the complexity of the flea-plague-prairie dog system and reiterate the importance of research on Yp transmission mechanisms to provide a full understanding of this disease. Our results also emphasize the importance of realistic estimates of spatial structure for exploring transmission dynamics of wildlife diseases and provide a framework for generating a data-driven description of spatial structure.

Ecological Modelling

U.S. Geological Survey science strategy to address chronic wasting disease and cervid health in 2024–2028

Chronic wasting disease (CWD), a neurological disease similar to scrapie in goats and sheep, has been spreading since the 1960s throughout cervid populations in the United States. It is currently detected in 30 States and now also extends to Canada, Korea, and Scandinavia. CWD is a fatal disease caused by an infectious abnormally folded prion protein. Population-level effects of CWD on localized subpopulations of white-tailed deer ( Odocoileus virginianus ), mule deer ( Odocoileus hemionus ), and elk ( Cervus elaphus ) have been documented. While susceptible to CWD, free-ranging moose ( Alces alces ) and reindeer ( Rangifer tarandus ) populations do not currently appear to be as severely affected. The mission of the U.S. Geological Survey (USGS) Chronic Wasting Disease and Cervid Health Science Team is to deliver integrated science to build resiliency into free-ranging cervid populations through more effective management of CWD, build capacity for ungulate health science, and enhance cervid health information sharing across USGS science centers and cooperative research units as well as with stakeholders. The USGS can play an important role in supporting regional and (or) national capacity building by providing resources and guidance to local, State, and Tribal management entities and by providing tools to enhance disease management. The USGS Ecosystems Mission Area’s Biological Threats and Invasive Species Research Program (BTRP) is the lead Federal program for free-ranging wildlife disease research and surveillance. The BTRP is relied upon by Congress, as well as local, State, and Tribal partners, to provide quality science that allows for informed decisions to be made about wildlife disease policy, planning, and management. The information provided by our research gives policy makers and the public the understanding needed to improve management preparedness and response. This document describes the U.S. Geological Survey Science Strategy To Address Chronic Wasting Disease and Cervid Health. It lays out a 5-year science strategy (2024–2028) for continued USGS research to study CWD in free-ranging cervids and their environments. The strategy includes improving detection methods, advancing our understanding of the mechanisms of transmission, incorporating the human dimensions and socio-economic effects of CWD in scientific studies, developing tools for decision making, and understanding potential effects of this disease on ecosystem health.

Circular

Ills in the pipeline: Emerging infectious diseases and wildlife

In the recent film Contagion, a medical thriller released in fall 2011, the fictitious MEV-1 virus&mdash;passed from bat to pig to humans&mdash;spreads across the globe as easily as the common cold, killing millions of humans and causing mass hysteria as medical researchers race to find a cure. Though it's Hollywood hyperbole, the film holds a kernel of truth: Researchers believe that the close proximity of Malaysian hog farms to forested areas&mdash;the natural habitat for fruit bats&mdash;allowed the previously unknown Nipah virus to spill from bats into pigs and subsequently into people, resulting in more than 100 human deaths (Epstein et al. 2006). There is no doubt that in recent times we have seen an unprecedented number of emerging infectious diseases, defined by the Institute for Medicine as new, reemerging, or drug-resistant infections whose incidence has increased or whose incidence threatens to increase in the near future. Many of these have a wildlife origin (Taylor et al. 2001). While this jump may be due, in part, to increased vigilance and reporting, there is a general consensus that current global conditions are creating a situation that is very favorable to the transmission of microbes that cause diseases. (For reviews, see Daszak et al. 2001 and Keesing et al. 2010). Likewise, it's increasingly important that wildlife professionals become aware of how and why new infectious diseases spread and what, if anything, can be done to minimize impacts on wildlife.

The Wildlife Professional

Report of the workshop on evidence-based design of national wildlife health programs

Summary This report summarizes a Wildlife Disease Association sponsored workshop held in 2016. The overall objective of the workshop was to use available evidence and selected subject matter expertise to define the essential functions of a National Wildlife Health Program and the resources needed to deliver a robust and reliable program, including the basic infrastructure, workforce, data and information systems, governance, organizational capacity, and essential features, such as wildlife disease surveillance, diagnostic services, and epidemiological investigation. This workshop also provided the means to begin the process of defining the essential attributes of a national wildlife health program that could be scalable and adaptable to each nation’s needs.

Open-File Report

Avian malaria in Hawaiian forest birds: Infection and population impacts across species and elevations

Wildlife diseases can present significant threats to ecological systems and biological diversity, as well as domestic animal and human health. However, determining the dynamics of wildlife diseases and understanding the impact on host populations is a significant challenge. In Hawai‘i, there is ample circumstantial evidence that introduced avian malaria ( Plasmodium relictum ) has played an important role in the decline and extinction of many native forest birds. However, few studies have attempted to estimate disease transmission and mortality, survival, and individual species impacts in this distinctive ecosystem. We combined multi-state capture-recapture (longitudinal) models with cumulative age-prevalence (cross-sectional) models to evaluate these patterns in Apapane, Hawai‘i Amakihi, and Iiwi in low-, mid-, and high-elevation forests on the island of Hawai‘i based on four longitudinal studies of 3–7 years in length. We found species-specific patterns of malaria prevalence, transmission, and mortality rates that varied among elevations, likely in response to ecological factors that drive mosquito abundance. Malaria infection was highest at low elevations, moderate at mid elevations, and limited in high-elevation forests. Infection rates were highest for Iiwi and Apapane, likely contributing to the absence of these species in low-elevation forests. Adult malaria fatality rates were highest for Iiwi, intermediate for Amakihi at mid and high elevations, and lower for Apapane; low-elevation Amakihi had the lowest malaria fatality, providing strong evidence of malaria tolerance in this low-elevation population. Our study indicates that hatch-year birds may have greater malaria infection and/or fatality rates than adults. Our study also found that mosquitoes prefer feeding on Amakihi rather than Apapane, but Apapane are likely a more important reservoir for malaria transmission to mosquitoes. Our approach, based on host abundance and infection rates, may be an effective alternative to mosquito blood meal analysis for determining vector-host contacts when mosquito densities are low and collection of blood-fed mosquitoes is impractical. Our study supports the hypothesis that avian malaria has been a primary factor influencing the elevational distribution and abundance of these three species, and likely limits other native Hawaiian species that are susceptible to malaria.

Hawai'i

Spatiotemporal causal inference with mechanistic ecological models: Evaluating targeted culling on chronic wasting disease dynamics in cervids

Spatiotemporal causal inference methods are needed to detect the effect of interventions on indirectly measured epidemiological outcomes that go beyond studying spatiotemporal correlations. Chronic wasting disease (CWD) causes neurological degeneration and eventual death to white-tailed deer ( Odocoileus virginianus ) in Wisconsin. Targeted culling involves removing deer after traditional hunting seasons in areas with high CWD prevalence. The evaluation of the causal effects of targeted culling in the spread and growth of CWD is an important unresolved research and CWD management question that can guide surveillance efforts. Reaction–diffusion partial differential equations (PDEs) can be used to mechanistically model the underlying spatiotemporal dynamics of wildlife diseases, like CWD, allowing researchers to make inference about unobserved epidemiological quantities. These models indirectly regress spatiotemporal covariates on diffusion and growth rates parameterizing such PDEs, obtaining associational conclusions. In this work we develop an innovative method to obtain causal estimators for the effect of targeted culling interventions on CWD epidemiological processes using an inverse-probability-of-treatment-weighted technique by means of marginal structural models embedded in the PDE fitting process. Additionally we establish a novel scheme for sensitivity analysis under unmeasured confounder for testing the hypothesis of a significant causal effect in the indirectly measured epidemiological outcomes. Our methods can be broadly used to study the impact of spatiotemporal interventions and treatment exposures in the epidemiological evolution of infectious diseases that can help to inform future efforts to mitigate public health implications and wildlife disease burden.

Wisconsin

Evidence of three new members of malignant catarrhal fever virus group in Muskox (Ovibos moschatus), Nubian ibex (Capra nubiana), and gemsbok (Oryx gazella)

Six members of the malignant catarrhal fever (MCF) virus group of ruminant rhadinoviruses have been identified to date. Four of these viruses are clearly associated with clinical disease: alcelaphine herpesvirus 1 (AlHV-1) carried by wildebeest (Connochaetes spp.); ovine herpesvirus 2 (OvHV-2), ubiquitous in domestic sheep; caprine herpesvirus 2 (CpHV-2), endemic in domestic goats; and the virus of unknown origin found causing classic MCF in white-tailed deer (Odocoileus virginianus; MCFV-WTD). Using serology and polymerase chain reaction with degenerate primers targeting a portion of the herpesviral DNA polymerase gene, evidence of three previously unrecognized rhadinoviruses in the MCF virus group was found in muskox (Ovibos moschatus), Nubian ibex (Capra nubiana), and gemsbok (South African oryx, Oryx gazella), respectively. Based on sequence alignment, the viral sequence in the muskox is most closely related to MCFV-WTD (81.5% sequence identity) and that in the Nubian ibex is closest to CpHV-2 (89.3% identity). The viral sequence in the gemsbok is most closely related to AlHV-1 (85.1% identity). No evidence of disease association with these viruses has been found. ?? Wildlife Disease Association 2003.

Journal of Wildlife Diseases

Habitat connectivity and host relatedness influence virus spread across an urbanising landscape in a fragmentation-sensitive carnivore

Spatially heterogeneous landscape factors such as urbanisation can have substantial effects on the severity and spread of wildlife diseases. However, research linking patterns of pathogen transmission to landscape features remains rare. Using a combination of phylogeographic and machine learning approaches, we tested the influence of landscape and host factors on feline immunodeficiency virus (FIV Lru ) genetic variation and spread among bobcats ( Lynx rufus ) sampled from coastal southern California. We found evidence for increased rates of FIV Lru lineage spread through areas of higher vegetation density. Furthermore, single-nucleotide polymorphism (SNP) variation among FIV Lru sequences was associated with host genetic distances and geographic location, with FIV Lru genetic discontinuities precisely correlating with known urban barriers to host dispersal. An effect of forest land cover on FIV Lru SNP variation was likely attributable to host population structure and differences in forest land cover between different populations. Taken together, these results suggest that the spread of FIV Lru is constrained by large-scale urban barriers to host movement. Although urbanisation at fine spatial scales did not appear to directly influence virus transmission or spread, we found evidence that viruses transmit and spread more quickly through areas containing higher proportions of natural habitat. These multiple lines of evidence demonstrate how urbanisation can change patterns of contact-dependent pathogen transmission and provide insights into how continued urban development may influence the incidence and management of wildlife disease.

California

White-Nose Syndrome Diagnostic Laboratory Network handbook

When responding to a wildlife disease outbreak, managers depend on consistent and clear data to make decisions. However, diagnostic methods for detecting pathogens of wildlife often lack the level of procedural and interpretational standardization that occurs in the investigation of human and domestic animal diseases. This lack of standardization can hamper diagnostic reliability in two ways. First is the inappropriate application of tests to new species or in situations that are outside of the original (in other words, validated) purpose. Second is the use of laboratory-specific modifications or analytical parameters without thorough investigation of how those changes affect result comparisons across institutions or the ability to make broader conclusions about pathogen or disease. White-nose syndrome (WNS) is a disease caused by the fungal pathogen Pseudogymnoascus destructans ( Pd ), which has spread rapidly and is causing population-level declines in some species of North American bats. During the last decade, quantitative polymerase chain reaction (qPCR) has become the most common method of testing for Pd because of qPCR’s speed, accuracy, and simplicity across a wide range of invasive and noninvasive sample types. Its widespread use by many State, Federal, Provincial, and academic institutions has inevitably led to variations in methodology and interpretation among laboratories. The progressive geographic spread of fungus and disease has also led to sampling contexts and strategies that differ from those for which the qPCR assay was originally developed and validated. These factors have resulted in inconsistencies among results tested in different laboratories and, subsequently, confusion for managers and decision makers. To address these challenges, the WNS National Response Team Diagnostic Working Group launched a project congruent with increased calls for the harmonization of wildlife disease diagnostic results, and reporting standards across disparate methodologies and laboratories. Beginning in 2019, interlaboratory testing was done to better understand how variations to Pd qPCR methodology affect diagnostic consistency and to reassess the assay’s fit for purpose in new testing contexts. This information led to expanded conversations within the Diagnostic Working Group related to best practices in Pd qPCR diagnostic testing, the development of common interpretation language for classifying test results, and the incorporation of that language into an updated WNS case definition. This handbook is the resulting product and is intended to help further harmonize Pd qPCR diagnostic testing by establishing recommendations related to voluntary participation in a WNS Diagnostic Laboratory Network, documenting the currently (2022) practiced Pd qPCR methodologies, discussing general best practices for molecular diagnostics and laboratory networks, and elaborating on the epidemiologic and diagnostic basis of the agreed-upon classification language for Pd qPCR results. Through this voluntary, consensus-based approach to diagnostic harmonization, this work aims to improve the confidence of management agencies in reported Pd qPCR results and can serve as an example of national diagnostic coordination for other unregulated wildlife diseases.

Techniques and Methods