Epidemiology of chronic wasting disease in captive white-tailed and mule deer

The natural occurrence of chronic wasting disease (CWD) in a 1993 cohort of captive white-tailed deer (Odocoileus virginianus) afforded the opportunity to describe epidemic dynamics in this species and to compare dynamics with those seen in contemporary cohorts of captive mule deer (O. hemionus) also infected with CWD. The overall incidence of clinical CWD in white-tailed deer was 82% (nine of 11) among individuals that survived >15 mo. Affected white-tailed deer died or were killed because of terminal CWD at age 49-76 mo (x = 59.6 mo, SE = 3.9 mo). Epidemic dynamics of CWD in captive white-tailed deer were similar to dynamics in mule deer cohorts. Incidence of clinical CWD was 57% (4/7) among hand-raised (HR) and 67% (4/6) among dam-raised (DR) mule deer; affected HR mule deer succumbed at 64-86 mo of age (x = 72 mo; SE = 5 mo), and affected DR mule deer died at age 31-58 mo (x = 41.3 mo; SE = 6.1 mo). Sustained horizontal transmission of CWD most plausibly explained epidemic dynamics, but the original source of exposures could not be determined. Apparent differences in mean age at CWD-caused death among these cohorts may be attributable to differences in the timing or intensity of exposure to CWD, and these factors appear to be more likely to influence epidemic dynamics than species differences. It follows that CWD epidemic dynamics in sympatric, free-ranging white-tailed and mule deer sharing habitats in western North American ranges also may be similar.     

Interaction among deer in a chronic wasting disease endemic zone

Although it is known that chronic wasting disease (CWD) can be transmitted by both direct animal-to-animal contact and contact with contaminated environments, the relative role of each mechanism in the spread of CWD in free-ranging populations has yet to be defined. We investigated patterns of interaction between mule deer (Odocoileus hemionus) in order to understand how factors such as season and landscape may influence patterns of disease spread in these populations. Using location data from male and female Global Positioning System (GPS)-collared mule deer in 5 study areas located in and around a CWD-endemic zone in southern Saskatchewan, Canada, we quantified close proximity events, or events involving both spatial and temporal overlap of individuals. We defined close proximity events as occurrences in which 2 deer were located <25 m apart at the same point in time. We looked at seasonal variation in the probability of close proximity events, as well as landscape factors associated with these events when compared to areas of shared space use, or spatial overlap alone. Overall probability of an individual GPS-collared deer being located in close proximity to another GPS-collared deer was 0.092 (n = 107). The early gestation (16 Dec–31 Mar) and late gestation (1 Apr–15 May) seasons had the highest probability of close proximity events occurring, and same-sex pairs were more likely to be found in close proximity than between-sex pairs during all seasons aside from the rut (1 Nov–15 Dec). High probability of close proximity events during the gestation seasons agrees with the tendency of mule deer to aggregate into large groups during late winter and suggests that this may be an important time period for CWD transmission to occur. Close proximity events occurred more in cropland and wetland than expected based on availability, whereas close proximity events occurred less than expected in grassland. The opposite was true for spatial overlap between individuals, which occurred more than expected in areas of low elevation and rugged terrain and in grassland or shrub–wood habitats. These results suggest that cropland may be a higher risk habitat for direct and indirect CWD transmission between individuals and that, although coulees and other areas of rugged topography are less likely to be associated with close proximity events, those areas may be more likely to contain environmental contamination in CWD-affected areas due to common use by multiple deer. © 2011 The Wildlife Society.     

Homogenization,sex, and differential motility predict spread of chronic wasting disease in mule deer in southern Utah

Chronic wasting disease (CWD) is an infectious prion disease that affects mule deer, along with other Cervids. It is a slow-developing, fatal disease which is rare in the free-ranging deer population of Utah. We present a sex-structured, spatial model for the spread of CWD over heterogeneous landscapes, incorporating both horizontal and environmental transmission pathways. To connect the local movement of deer to the regional spread of CWD, we use ecological diffusion with motility coefficients estimated from mule deer movement data. Ecological diffusion allows for aggregation of populations in desirable habitats and therefore allows for an interaction between density dependent disease transmission and landscape structure. The major innovation presented is use of homogenization to accelerate simulations of disease spread in southeastern Utah, from the La Sal Mountains near Moab to the Abajo Mountains near Monticello. The homogenized model provides accuracy while maintaining fidelity to small-scale habitat effects on deer distribution, including differential aggregation in land cover types with high residence times, with errors comparable to the order parameter measuring separation of small and large scales ( \(\epsilon \approx .01\) in this case). We use the averaged coefficients from the homogenized model to explore asymptotic invasion speed and the impact of current population size on disease spread in southeastern Utah.     

Evaluating Spatial Overlap and Relatedness of White-tailed Deer in a Chronic Wasting Disease Management Zone

Wildlife disease transmission, at a local scale, can occur from interactions between infected and susceptible conspecifics or from a contaminated environment. Thus, the degree of spatial overlap and rate of contact among deer is likely to impact both direct and indirect transmission of infectious diseases such chronic wasting disease (CWD) or bovine tuberculosis. We identified a strong relationship between degree of spatial overlap (volume of intersection) and genetic relatedness for female white-tailed deer in Wisconsin’s area of highest CWD prevalence. We used volume of intersection as a surrogate for contact rates between deer and concluded that related deer are more likely to have contact, which may drive disease transmission dynamics. In addition, we found that age of deer influences overlap, with fawns exhibiting the highest degree of overlap with other deer. Our results further support the finding that female social groups have higher contact among related deer which can result in transmission of infectious diseases. We suggest that control of large social groups comprised of closely related deer may be an effective strategy in slowing the transmission of infectious pathogens, and CWD in particular.     

Epidemiology of chronic wasting disease in free-ranging mule deer: spatial, temporal, and demographic influences on observed prevalence patterns

We analyzed chronic wasting disease (CWD) prevalence data from mule deer populations in northcentral Colorado, USA, to discern the likely influences of temporal, spatial, and demographic factors on patterns observed in naturally infected populations. In addition to reaffirming spatial heterogeneity among wintering mule deer subpopulations, we report marked differences in CWD prevalence by sex and age groups as well as clear local trends of increasing prevalence over a 7-yr period. Prevalence of CWD differed by age (yearling vs. adult), sex, and geographic area at two different spatial scales (game management unit or population unit winter range) and increased over time at both geographic scales. Disease status (positive or negative) was not independent of age for males (n=285, df=6, chi2=18.4, P=0.005) or females (n=387, df=8, chi2=17.2, P=0.028). Among males, prevalence increased and then declined across age classes, peaking in 5- to 6-yr-old individuals; among females, prevalence showed no definite age-related pattern. Demographic, spatial, and temporal factors all appear to contribute to the marked heterogeneity in CWD prevalence in endemic portions of northcentral Colorado, USA. These factors likely combine in various ways to influence epidemic dynamics on both local and broad geographic scales.     

Experimental oral transmission of chronic wasting disease to reindeer (Rangifer tarandus tarandus)

Chronic wasting disease (CWD), a transmissible spongiform encephalopathy of cervids, remains prevalent in North American elk, white-tailed deer and mule deer. A natural case of CWD in reindeer (Rangifer tarandus tarandus) has not been reported despite potential habitat overlap with CWD-infected deer or elk herds. This study investigates the experimental transmission of CWD from elk or white-tailed deer to reindeer by the oral route of inoculation. Ante-mortem testing of the three reindeer exposed to CWD from white-tailed deer identified the accumulation of pathological PrP (PrP(CWD)) in the recto-anal mucosa associated lymphoid tissue (RAMALT) of two reindeer at 13.4 months post-inoculation. Terminal CWD occurred in the two RAMALT-positive reindeer at 18.5 and 20 months post-inoculation while one other reindeer in the white-tailed deer CWD inoculum group and none of the 3 reindeer exposed to elk CWD developed disease. Tissue distribution analysis of PrP(CWD) in CWD-affected reindeer revealed widespread deposition in central and peripheral nervous systems, lymphoreticular tissues, the gastrointestinal tract, neuroendocrine tissues and cardiac muscle. Analysis of prion protein gene (PRNP) sequences in the 6 reindeer identified polymorphisms at residues 2 (V/M), 129 (G/S), 138 (S/N) and 169 (V/M). These findings demonstrate that (i) a sub-population of reindeer are susceptible to CWD by oral inoculation implicating the potential for transmission to other Rangifer species, and (ii) certain reindeer PRNP polymorphisms may be protective against CWD infection.     

Estimating chronic wasting disease effects on mule deer recruitment and population growth

Chronic wasting disease (CWD), a prion disease of mule deer (Odocoileus hemionus), accelerates mortality and in so doing has the potential to influence population dynamics. Although effects on mule deer survival are clear, how CWD affects recruitment is less certain. We studied how prion infection influenced the number of offspring raised to weaning per adult (≥2 yr old) female mule deer and subsequently the estimated growth rate (λ) of an infected deer herd. Infected and presumably uninfected radio-collared female deer were observed with their fawns in late summer (August-September) during three consecutive years (2006-2008) in the Table Mesa area of Boulder, Colorado, USA. We counted the number of fawns accompanying each female, then used a fully Bayesian model to estimate recruitment by infected and uninfected females and the effect of the disease on λ. On average, infected females weaned 0.95 fawns (95% credible interval=0.56-1.43) whereas uninfected females weaned 1.34 fawns (95% credible interval=1.09-1.61); the probability that uninfected females weaned more fawns than infected females was 0.93). We used estimates of prevalence to weight recruitment and survival parameters in the transition matrix of a three-age, single-sex matrix model and then used the matrix to calculate effects of CWD on λ. When effects of CWD on both survival and recruitment were included, the modeled λ was 0.97 (95% credible interval = 0.82-1.09). Effects of disease on λ were mediated almost entirely by elevated mortality of infected animals. We conclude that although CWD may affect mule deer recruitment, these effects seem to be sufficiently small that they can be omitted in estimating the influences of CWD on population growth rate.     

Failure of fallow deer (Dama dama) to develop chronic wasting disease when exposed to a contaminated environment and infected mule deer (Odocoileus hemionus)

We monitored a herd of fallow deer (Dama dama) for evidence of prion infection for 7 yr by periodic postmortem examination of animals from the herd. The fallow deer were exposed to the chronic wasting disease (CWD) agent from mule deer by living in a paddock considered contaminated with infectivity from its history of housing CWD infected deer and, after the first year of the study, by comingling with infected mule deer (Odocoileus hemionus). At least 8 of 12 mule deer serving as sentinels for prion transmission and 25 additional mule deer serving as sources of infectivity developed clinical CWD or were otherwise confirmed to be infected with CWD via lymphoid tissue immunohistochemistry (IHC). In contrast, none of the 41 exposed fallow deer showed clinical signs suggestive of CWD, IHC staining of disease-associated prion in lymphoid or brain tissues, or evidence of spongiform degeneration in sections of brain stem at the level of the obex when sampled 18 mo to 7 yr after entering the mule deer paddock. The absence of clinical disease and negative IHC results in fallow deer housed in the same contaminated paddock for up to 7 yr and almost continuously exposed to CWD-infected mule deer for up to 6 yr suggests a species barrier or other form of resistance preventing fallow deer infection by the CWD agent or delaying progression of the disease in this species.     

Detection and Avoidance of Predators in White-Tailed Deer (Odocoileus virginianus) and Mule Deer (O. hemionus)

In this paper, we investigate the relationship between early detection of predators and predator avoidance in white-tailed deer ( Odocoileus virginianus ) and mule deer ( O. hemionus ), two closely related species that differ in their habitat preferences and in their anti-predator behavior. We used observations of coyotes ( Canis latrans ) hunting deer to test whether the distance at which white-tails and mule deer alerted to coyotes was related to their vulnerability to predation. Coyote encounters with both species were more likely to escalate when deer alerted at shorter distances. However, coyote encounters with mule deer progressed further than encounters with white-tails that alerted at the same distance, and this was not due to species differences in group size or habitat. We then conducted an experiment in which a person approached groups of deer to compare the detection abilities and the form of alert response for white-tails and mule deer, and for age groups within each species. Mule deer alerted to the approacher at longer distances than white-tails, even after controlling for variables that were potentially confounding. Adult females of both species alerted sooner than conspecific juveniles. Mule deer almost always looked directly at the approacher as their initial response, whereas white-tails were more likely to flee or to look in another direction with no indication that they pinpointed the approacher during the trial. Mule deer may have evolved the ability to detect predators earlier than white-tails as an adaptation to their more open habitats, or because they need more time to coordinate subsequent anti-predator defenses.     

Interspecies transmission of chronic wasting disease prions to squirrel monkeys (Saimiri sciureus)

Chronic wasting disease (CWD) is an emerging prion disease of deer and elk. The risk of CWD transmission to humans following exposure to CWD-infected tissues is unknown. To assess the susceptibility of nonhuman primates to CWD, two squirrel monkeys were inoculated with brain tissue from a CWD-infected mule deer. The CWD-inoculated squirrel monkeys developed a progressive neurodegenerative disease and were euthanized at 31 and 34 months postinfection. Brain tissue from the CWD-infected squirrel monkeys contained the abnormal isoform of the prion protein, PrP-res, and displayed spongiform degeneration. This is the first reported transmission of CWD to primates.     

Mother to Offspring Transmission of Chronic Wasting Disease in Reeves’ Muntjac Deer

The horizontal transmission of prion diseases has been well characterized in bovine spongiform encephalopathy (BSE), chronic wasting disease (CWD) of deer and elk and scrapie of sheep, and has been regarded as the primary mode of transmission. Few studies have monitored the possibility of vertical transmission occurring within an infected mother during pregnancy. To study the potential for and pathway of vertical transmission of CWD in the native cervid species, we used a small cervid model–the polyestrous breeding, indoor maintainable, Reeves’ muntjac deer–and determined that the susceptibility and pathogenesis of CWD in these deer reproduce that in native mule and white-tailed deer. Moreover, we demonstrate here that CWD prions are transmitted from doe to fawn. Maternal CWD infection also appears to result in lower percentage of live birth offspring. In addition, evolving evidence from protein misfolding cyclic amplification (PMCA) assays on fetal tissues suggest that covert prion infection occurs in utero. Overall, our findings demonstrate that transmission of prions from mother to offspring can occur, and may be underestimated for all prion diseases.     

Relative vulnerability of chronic wasting disease infected mule deer to vehicle collisions

We estimated chronic wasting disease (CWD) prevalence among vehicle-killed mule deer (Odocoileus hemionus) in select data analysis units (DAUs) in northern Colorado, USA, and compared these with estimated CWD prevalence among mule deer of the same sex sampled in the vicinity of collision sites to assess relative vulnerability of CWD-infected individuals to vehicle collisions. Twenty-five of 171 vehicle-killed mule deer tested positive for CWD (overall prevalence=0.146, 95% confidence interval [CI]=0.097-0.208); 173 of 2,317 deer sampled in the vicinity of these vehicle-killed deer tested positive (overall prevalence=0.075, 95% CI=0.064-0.085). In nine of ten DAU x sex comparisons, relative risk of CWD infection tended to be higher among vehicle-killed deer (range of estimated relative risks=1.6-15.9). Spongiform encephalopathy was detected in 12 of 20 (60%; 95% CI=39-81%) CWD-positive deer killed by vehicles and in 79 of 180 (44%; 95% CI=37-52%) CWD-positive deer detected via random sampling (relative risk=1.37; 95% CI=0.92-2.03), suggesting that infected deer killed by vehicles tended to be in later stages of disease than those killed by hunters. Our data offer evidence that CWD-infected mule deer may be relatively vulnerable to vehicle collisions. It follows that sampling of vehicle-killed mule deer may be exploited to increase efficiency of surveillance programs designed to detect new foci of CWD infection; moreover, evidence of increased susceptibility to vehicle collisions may aid in understanding vulnerability of CWD-infected individuals to other forms of death, particularly predation.     

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.     

Bayesian Modeling of Prion Disease Dynamics in Mule Deer Using Population Monitoring and Capture-Recapture Data

Epidemics of chronic wasting disease (CWD) of North American Cervidae have potential to harm ecosystems and economies. We studied a migratory population of mule deer (Odocoileus hemionus) affected by CWD for at least three decades using a Bayesian framework to integrate matrix population and disease models with long-term monitoring data and detailed process-level studies. We hypothesized CWD prevalence would be stable or increase between two observation periods during the late 1990s and after 2010, with higher CWD prevalence making deer population decline more likely. The weight of evidence suggested a reduction in the CWD outbreak over time, perhaps in response to intervening harvest-mediated population reductions. Disease effects on deer population growth under current conditions were subtle with a 72% chance that CWD depressed population growth. With CWD, we forecasted a growth rate near one and largely stable deer population. Disease effects appear to be moderated by timing of infection, prolonged disease course, and locally variable infection. Long-term outcomes will depend heavily on whether current conditions hold and high prevalence remains a localized phenomenon.     

Prevalence of chronic wasting disease and bovine tuberculosis in free-ranging deer and elk in South Dakota

Heads of hunter-harvested deer and elk were collected throughout South Dakota (USA) and within established chronic wasting disease (CWD) surveillance areas from 1997-2002 to determine infection with CWD and bovine tuberculosis (TB). We used immunohistochemistry to detect CWD-infected individuals among 1,672 deer and elk sampled via geographically targeted surveillance. A total of 537 elk (Cervus elaphus nelsoni), 813 white-tailed deer (Odocoileus virginianus), and 322 mule deer (O. hemionus) was sampled for CWD. Estimated overall prevalence and associated confidence intervals (95%) in white-tailed deer was 0.001% (0-0.007%). Similarly, estimated overall prevalence in elk and mule deer was 0.0% (0-0.004%) and 0.0% (0-0.011%), respectively. A total of 401 elk, 1,638 white-tailed deer, and 207 mule deer was sampled for TB. Estimated overall prevalence of infection with TB in elk harvested in South Dakota was 0.0% (0-0.009%). Similarly, estimated overall prevalence of TB in white-tailed deer and mule deer harvested throughout South Dakota was 0.0% (0-0.002%) and 0.0% (0-0.018%), respectively.     

Tonsillar biopsy test for chronic wasting disease: Two sampling approaches in mule deer and white-tailed deer

Preclinical antemortem testing of deer (Odocoileus spp.) for chronic wasting disease (CWD) can be important for determining prevalence rates and removing infected individuals from wild populations. Because samples with high numbers of tonsillar follicles are likely to provide earlier detection of CWD than samples with fewer follicles, the method of obtaining follicular samples may be critical when investigating disease prevalence. Between January 2003 and January 2005, white-tailed deer (O. virginianus) in southeast and southwest Minnesota and white-tailed and mule deer (O. hemionus) in Wind Cave National Park, South Dakota, were sampled using dorso-lateral and ventral-medial approaches for collecting tonsillar follicles. We obtained significantly more follicles using a dorso-lateral (median number of follicles = 19) rather than a ventral-medial (median number of follicles = 5.5) approach. No differences were observed in collection of tonsillar follicles that were related to sex, age class, or species of deer. We recommend the dorso-lateral approach for assessing CWD prevalence in deer populations.     

Inhibition of protease-resistant prion protein formation in a transformed deer cell line infected with chronic wasting disease

Chronic wasting disease (CWD) is an emerging transmissible spongiform encephalopathy (prion disease) of North American cervids, i.e., mule deer, white-tailed deer, and elk (wapiti). To facilitate in vitro studies of CWD, we have developed a transformed deer cell line that is persistently infected with CWD. Primary cultures derived from uninfected mule deer brain tissue were transformed by transfection with a plasmid containing the simian virus 40 genome. A transformed cell line (MDB) was exposed to microsomes prepared from the brainstem of a CWD-affected mule deer. CWD-associated, protease-resistant prion protein (PrP(CWD)) was used as an indicator of CWD infection. Although no PrP(CWD) was detected in any of these cultures after two passes, dilution cloning of cells yielded one PrP(CWD)-positive clone out of 51. This clone, designated MDB(CWD), has maintained stable PrP(CWD) production through 32 serial passes thus far. A second round of dilution cloning yielded 20 PrP(CWD)-positive subclones out of 30, one of which was designated MDB(CWD2). The MDB(CWD2) cell line was positive for fibronectin and negative for microtubule-associated protein 2 (a neuronal marker) and glial fibrillary acidic protein (an activated astrocyte marker), consistent with derivation from brain fibroblasts (e.g., meningeal fibroblasts). Two inhibitors of rodent scrapie protease-resistant PrP accumulation, pentosan polysulfate and a porphyrin compound, indium (III) meso-tetra(4-sulfonatophenyl)porphine chloride, potently blocked PrP(CWD) accumulation in MDB(CWD) cells. This demonstrates the utility of these cells in a rapid in vitro screening assay for PrP(CWD) inhibitors and suggests that these compounds have potential to be active against CWD in vivo.     

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.     

Epizootiology of chronic wasting disease in free-ranging cervids in Colorado and Wyoming

Surveillance and epidemic modeling were used to study chronic wasting disease (CWD), a transmissible spongiform encephalopathy that occurs naturally among sympatric, free-ranging deer (Odocoileus spp.) and Rocky Mountain elk (Cervus elaphus nelsoni) populations in contiguous portions of northeastern Colorado and southeastern Wyoming (USA). We used clinical case submissions to identify endemic areas, then used immunohistochemistry to detect CWD-infected individuals among 5,513 deer and elk sampled via geographically-focused random surveys. Estimated overall prevalence (prevalence, 95% confidence interval) in mule deer (4.9%, 4.1 to 5.7%) was higher than in white-tailed deer (2.1%, 0.5 to 3.4%) or elk (0.5%, 0.001 to 1%) in endemic areas; CWD was not detected in outlying portions of either state. Within species, CWD prevalence varied widely among biologically- or geographically-segregated subpopulations within the 38,137 km2 endemic area but appeared stable over a 3-yr period. The number of clinical CWD cases submitted from an area was a poor predictor of local CWD prevalence, and prevalence was typically > or =1% before clinical cases were first detected in most areas. Under plausible transmission assumptions that mimicked field data, prevalence in epidemic models reached about 1% in 15 to 20 yr and about 15% in 37 to 50 yr. Models forecast population declines once prevalence exceeded about 5%. Both field and model data supported the importance of lateral transmission in CWD dynamics. Based on prevalence, spatial distribution, and modeling, we suggest CWD has been occurring in northeastern Colorado and southeastern Wyoming for >30 yr, and may be best represented as an epizootic with a protracted time-scale.