Julia A. Langenberg

Infectious prions in pre-clinical deer and transmission of chronic wasting disease solely by environmental exposure.

Key to understanding the epidemiology and pathogenesis of prion diseases, including chronic wasting disease (CWD) of cervids, is determining the mode of transmission from one individual to another. We have previously reported that saliva and blood from CWD-infected deer contain sufficient infectious prions to transmit disease upon passage into naïve deer. Here we again use bioassays in deer to show that blood and saliva of pre-symptomatic deer contain infectious prions capable of infecting naïve deer and that naïve deer exposed only to environmental fomites from the suites of CWD-infected deer acquired CWD infection after a period of 15 months post initial exposure. These results help to further explain the basis for the facile transmission of CWD, highlight the complexities associated with CWD transmission among cervids in their natural environment, emphasize the potential utility of blood-based testing to detect pre-clinical CWD infection, and could augur similar transmission dynamics in other prion infections.

SPATIAL EPIDEMIOLOGY OF CHRONIC WASTING DISEASE IN WISCONSIN WHITE-TAILED DEER

Chronic wasting disease (CWD) is a fatal, emerging disease of cervids associated with transmissible protease-resistant prion proteins. The potential for CWD to cause dramatic declines in deer and elk populations and perceived human health risks associated with consuming CWD-contaminated venison have led wildlife agencies to embark on extensive CWD control programs, typically involving culling to reduce deer populations. We characterized the spatial distribution of CWD in white-tailed deer (Odocoileus virginianus) in Wisconsin to facilitate CWD management. We found that CWD prevalence declined with distance from a central location, was locally correlated at a scale of 3.6 km, and was correlated with deer habitat abundance. The latter result is consistent with patterns expected for a positive relationship between density and prevalence of CWD. We recommend management activities focused on culling in geographic areas with high prevalence to have the greatest probability of removing infected individuals. Further research is needed to elucidate the factors involved in CWD spread and infection rates, especially the role of density-dependent transmission.

Landscape genetics and the spatial distribution of chronic wasting disease

Predicting the spread of wildlife disease is critical for identifying populations at risk, targeting surveillance and designing proactive management programmes. We used a landscape genetics approach to identify landscape features that influenced gene flow and the distribution of chronic wasting disease (CWD) in Wisconsin white-tailed deer. CWD prevalence was negatively correlated with genetic differentiation of study area deer from deer in the area of disease origin (core-area). Genetic differentiation was greatest, and CWD prevalence lowest, in areas separated from the core-area by the Wisconsin River, indicating that this river reduced deer gene flow and probably disease spread. Features of the landscape that influence host dispersal and spatial patterns of disease can be identified based on host spatial genetic structure. Landscape genetics may be used to predict high-risk populations based on their genetic connection to infected populations and to target disease surveillance, control and preventative activities.

Linking process to pattern: estimating spatiotemporal dynamics of a wildlife epidemic from cross-sectional data

Underlying dynamic event processes unfolding in continuous time give rise to spatiotemporal patterns that are sometimes observable at only a few discrete times. Such event processes may be modulated simultaneously over several spatial (e.g., latitude and longitude) and temporal (e.g., age, calendar time, and cohort) dimensions. The ecological challenge is to understand the dynamic latent processes that were integrated over several dimensions (space and time) to produce the observed pattern: a so-called inverse problem. An example of such a problem is characterizing epidemiological rate processes from spatially referenced age-specific prevalence data for a wildlife disease such as chronic wasting disease (CWD). With age-specific prevalence data, the exact infection times are not observed, which complicates the direct estimation of rates. However, the relationship between the observed data and the unobserved rate variables can be described with likelihood equations. Typically, for problems with multiple timescales, the likelihoods are integral equations without closed forms. The complexity of the likelihoods often makes traditional maximum-likelihood approaches untenable. Here, using seven years of hunter-harvest prevalence data from the CWD epidemic in white-tailed deer (Odocoileus virginianus) in Wisconsin, USA, we develop and explore a Bayesian approach that allows for a detailed examination of factors modulating the infection rates over space, age, and time, and their interactions. Our approach relies on the Bayesian ability to borrow strength from neighbors in both space and time. Synthesizing a number of areas of event time analysis (current-status data, age/period/cohort models, Bayesian spatial shared frailty models), our general framework has very broad ecological applicability beyond disease prevalence data to a number of important ecological event time analyses, including general survival studies with multiple time dimensions for which existing methodology is limited. We observed strong associations of infection rates with age, gender, and location. The infection rate appears to be increasing with time. We could not detect growth hotspots, or location by time interactions, which suggests that spatial variation in infection rates is determined primarily by when the disease arrives locally, rather than how fast it grows. We emphasize assumptions and the potential consequences of their violations.

Chronic Wasting Disease (CWD) Susceptibility of Several North American Rodents That Are Sympatric with Cervid CWD Epidemics

ABSTRACT Chronic wasting disease (CWD) is a highly contagious always fatal neurodegenerative disease that is currently known to naturally infect only species of the deer family, Cervidae. CWD epidemics are occurring in free-ranging cervids at several locations in North America, and other wildlife species are certainly being exposed to infectious material. To assess the potential for transmission, we intracerebrally inoculated four species of epidemic-sympatric rodents with CWD. Transmission was efficient in all species; the onset of disease was faster in the two vole species than the two Peromyscus spp. The results for inocula prepared from CWD-positive deer with or without CWD-resistant genotypes were similar. Survival times were substantially shortened upon second passage, demonstrating adaptation. Unlike all other known prion protein sequences for cricetid rodents that possess asparagine at position 170, our red-backed voles expressed serine and refute previous suggestions that a serine in this position substantially reduces susceptibility to CWD. Given the scavenging habits of these rodent species, the apparent persistence of CWD prions in the environment, and the inevitable exposure of these rodents to CWD prions, our intracerebral challenge results indicate that further investigation of the possibility of natural transmission is warranted.

White‐Tailed Deer Harvest From the Chronic Wasting Disease Eradication Zone in South‐Central Wisconsin

Abstract Chronic wasting disease (CWD) was discovered in free-ranging white-tailed deer (Odocoileus virginianus) in south-central Wisconsin in 2002. The current control method for CWD in the state is the harvest of deer from affected areas to reduce population density and lower CWD transmission. We used spatial regression methods to identify factors associated with deer harvest across south-central Wisconsin. Harvest of deer by hunters was positively related to deer density (slope = 0.003, 95% CI = 0.0001–0.006), the number of landowners that requested harvest permits (slope = 0.071, 95% CI = 0.037–0.105), and proximity to the area of highest CWD infection (slope = −0.041, 95% CI = −0.056–−0.027). Concomitantly, harvest was not impacted in areas where landowners signed a petition protesting intensive deer reduction (slope = −0.00006, 95% CI = −0.0005–0.0003). Our results suggest that the success of programs designed to reduce deer populations for disease control or to reduce overabundance in Wisconsin are dependent on landowner and hunter participation. We recommend that programs or actions implemented to eradicate or mitigate the spread of CWD should monitor and assess deer population reduction and evaluate factors affecting program success to improve methods to meet management goals.

SURVEILLANCE TO DETECT CHRONIC WASTING DISEASE IN WHITE-TAILED DEER IN WISCONSIN

Chronic wasting disease (CWD), a prion disease affecting North American cervids, has been discovered in at least 12 states and provinces throughout the continent. Since 2002, a number of states and provinces have initiated surveillance programs to detect CWD in native cervid populations. However, many questions remain about the appropriate methods, geographic scope, and number of samples required for an effective CWD surveillance program. We provide an improved statistical method to calculate the probability of detecting CWD in primary sample units (e.g., county or deer management unit) that also considers deer abundance and the nonrandom distribution of CWD and hunter harvests. We used this method to analyze data from a statewide CWD detection program conducted in Wisconsin during the autumns of 2002 and 2003 to determine the distribution of CWD in white-tailed deer (Odocoileus virginianus). Deer heads were collected at hunter registration stations, and brainstem (obex) and retropharyngeal lymph nodes were removed for disease testing. Our analysis includes samples from >35,000 deer collected outside the known affected area. The probability of detecting chronic wasting disease at a prevalence of 1% varied from 0.89 to ≥0.99 among the 56 primary sample units. Detection probabilities for 1% CWD prevalence were >0.9 in 55 primary sample units, and >0.99 in 10. Detection probabilities will be higher in areas where CWD prevalence exceeds 1%. CWD-positive deer were detected in eight primary sample units surrounding the known affected area during surveillance activities. Our approach provides a novel statistical technique to accommodate nonrandom sampling in wildlife disease surveillance programs.

Genetic susceptibility to chronic wasting disease in free-ranging white-tailed deer: Complement component C1q and Prnp polymorphisms §

The genetic basis of susceptibility to chronic wasting disease (CWD) in free-ranging cervids is of great interest. Association studies of disease susceptibility in free-ranging populations, however, face considerable challenges including: the need for large sample sizes when disease is rare, animals of unknown pedigree create a risk of spurious results due to population admixture, and the inability to control disease exposure or dose. We used an innovative matched case-control design and conditional logistic regression to evaluate associations between polymorphisms of complement C1q and prion protein (Prnp) genes and CWD infection in white-tailed deer from the CWD endemic area in south-central Wisconsin. To reduce problems due to admixture or disease-risk confounding, we used neutral genetic (microsatellite) data to identify closely related CWD-positive (n=68) and CWD-negative (n=91) female deer to serve as matched cases and controls. Cases and controls were also matched on factors (sex, location, age) previously demonstrated to affect CWD infection risk. For Prnp, deer with at least one Serine (S) at amino acid 96 were significantly less likely to be CWD-positive relative to deer homozygous for Glycine (G). This is the first characterization of genes associated with the complement system in white-tailed deer. No tests for association between any C1q polymorphism and CWD infection were significant at p<0.05. After controlling for Prnp, we found weak support for an elevated risk of CWD infection in deer with at least one Glycine (G) at amino acid 56 of the C1qC gene. While we documented numerous amino acid polymorphisms in C1q genes none appear to be strongly associated with CWD susceptibility.

LEVELS OF FECAL CORTICOSTERONE IN SANDHILL CRANES DURING A HUMAN-LED MIGRATION

Fourteen captive-reared greater sandhill cranes (Grus canadensis tabida) were conditioned to follow ultralight aircraft to promote migration between Wisconsin and Florida (USA) after release. Fecal samples were collected throughout the training period in Wisconsin and during a 1,977-km human-led migration to Florida to determine fecal corticosterone (FC) concentrations by radioimmunoassay. The mean (±SE) FC concentration during the training period was 109.5±7.5 ng/g and was representative of baseline levels recorded previously from sandhill cranes. Fecal corticosterone concentrations increased in early migration compared to concentrations 1 mo prior to departure (P<0.01) but were not different from baseline concentrations at the end of the 6-wk migration period. The variability of FC concentrations in individual samples was greater throughout the migration than the training period. Increases in FC during migration were modest and generally consistent with normal corticosterone elevations observed in migrating birds.

Rejoinder: sifting through model space

DENNIS M. HEISEY, ERIK E. OSNAS, PAUL C. CROSS, DAMIEN O. JOLY, JULIA A. LANGENBERG, AND MICHAEL W. MILLER USGS, National Wildlife Health Center, Madison, Wisconsin 53711 USA Department of Forest and Wildlife Ecology, University of Wisconsin, 1630 Linden Drive, Madison, Wisconsin 52706 USA USGS, Northern Rocky Mountain Science Center, Bozeman, Montana 59717 USA Global Health Programs, Wildlife Conservation Society, 1008 Beverly Drive, Nanaimo, British Columbia V9S 2S4 Canada Wisconsin Department of Natural Resources, 101 South Webster Street, Madison, Wisconsin 53703 USA Colorado Division of Wildlife, Wildlife Research Center, 317 West Prospect Road, Fort Collins, Colorado 80526-2097 USA