Contagious Prion Disease Research Articles

Circulation of prions within dust on a scrapie affected farm.

Prion diseases are fatal neurological disorders that affect humans and animals. Scrapie of sheep/goats and Chronic Wasting Disease (CWD) of deer/elk are contagious prion diseases where environmental reservoirs have a direct link to the transmission of disease. Using protein misfolding cyclic amplification we demonstrate that scrapie PrPSc can be detected within circulating dusts that are present on a farm that is naturally contaminated with sheep scrapie. The presence of infectious scrapie within airborne dusts may represent a possible route of infection and illustrates the difficulties that may be associated with the effective decontamination of such scrapie affected premises.

Persistence of ovine scrapie infectivity in a farm environment following cleaning and decontamination

Scrapie of sheep/goats and chronic wasting disease of deer/elk are contagious prion diseases where environmental reservoirs are directly implicated in the transmission of disease. In this study, the effectiveness of...

Survival and population growth of a free‐ranging elk population with a long history of exposure to chronic wasting disease

ABSTRACTInvestigations of chronic wasting disease (CWD), a fatal, contagious prion disease of free‐ranging cervids, suggest the disease can cause long‐term population declines in deer (Odocoileus spp.). However, the implications of CWD for elk (Cervus elaphus nelsoni) populations are less certain. During 2008–2010, we used rectal biopsies and telemetry to observe disease transmission and survival in adult female elk from a high‐density herd in Rocky Mountain National Park (RMNP) that had been infected by CWD for over 25 years. We studied a cohort of 123 adult female elk that were determined to be free of CWD by rectal biopsy in 2008. Annual incidence of CWD was 0.08 [95% Bayesian credible interval (BCI) = 0.05, 0.12]. Annual survival probabilities of the cohort excluding harvest declined from 0.97 in 2008 (BCI = 0.93, 0.99) to 0.85 in 2010 (BCI = 0.75, 0.93). Declines in survival were attributed almost entirely to CWD; the proportion of radiocollared elk that died of CWD increased from 0.02 in 2008 (BCI = 0.00, 0.05) to 0.11 in 2010 (BCI = 0.04, 0.21). We attributed the increase to the time lag required for development of new CWD cases. We used survival rates of susceptible and infected elk to develop a projection matrix for a discrete time, female only model that estimated the intrinsic population growth rate (λ) of this elk herd to be 1.00 (BCI = 0.93, 1.05) using the prevalence of CWD (12.9%) and calf:cow ratios (24:100) observed during this study. Population declines were predicted to occur when prevalence of CWD exceeded 13% (BCI = 0, 35). However, this estimate was contingent on calf:cow ratios and harvest. Greater recruitment will offset some of the effects of CWD, whereas the inclusion of female harvest, which was excluded from this study, would likely result in lower λ values than those observed in this study. We conclude that CWD can exceed natural rates of mortality, reduce survival of adult females, and decrease population growth of elk herds. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.

THE ROLE OF PREDATION IN DISEASE CONTROL: A COMPARISON OF SELECTIVE AND NONSELECTIVE REMOVAL ON PRION DISEASE DYNAMICS IN DEER

Effective measures for controlling chronic wasting disease (CWD), a contagious prion disease of cervids, remain elusive. We review theoretic relationships between predation and host-parasite dynamics and describe a mathematical model to evaluate the potential influence of random removal through harvest or culling and selective predation by wolves (Canis lupus) upon CWD dynamics in deer (Odocoileus spp.) populations. Imposing nonselective mortality representing a 15% annual harvest or cull 51 yr after CWD introduction lowered both deer population size and steady state CWD. Selective (4×) mortality at the same 15% predation rate caused a more modest reduction in deer population size accompanied by a relatively rapid decline in CWD prevalence and elimination of the disease from a closed population. The impacts of selective predation on epidemic dynamics were sensitive to assumptions on parameter estimates; however, within expected ranges, the results of selective predation were consistent and robust. We suggest that as CWD distribution and wolf range overlap in the future, wolf predation may suppress disease emergence or limit prevalence.

Lions and Prions and Deer Demise

BackgroundContagious prion diseases – scrapie of sheep and chronic wasting disease of several species in the deer family – give rise to epidemics that seem capable of compromising host population viability. Despite this prospect, the ecological consequences of prion disease epidemics in natural populations have received little consideration.Methodology/Principal FindingsUsing a cohort study design, we found that prion infection dramatically lowered survival of free-ranging adult (>2-year-old) mule deer (Odocoileus hemionus): estimated average life expectancy was 5.2 additional years for uninfected deer but only 1.6 additional years for infected deer. Prion infection also increased nearly fourfold the rate of mountain lions (Puma concolor) preying on deer, suggesting that epidemics may alter predator–prey dynamics by facilitating hunting success. Despite selective predation, about one fourth of the adult deer we sampled were infected. High prevalence and low survival of infected deer provided a plausible explanation for the marked decline in this deer population since the 1980s.ConclusionRemarkably high infection rates sustained in the face of intense predation show that even seemingly complete ecosystems may offer little resistance to the spread and persistence of contagious prion diseases. Moreover, the depression of infected populations may lead to local imbalances in food webs and nutrient cycling in ecosystems in which deer are important herbivores.

Faecal shedding, alimentary clearance and intestinal spread of prions in hamsters fed with scrapie

Shedding of prions via faeces may be involved in the transmission of contagious prion diseases. Here, we fed hamsters 10 mg of 263K scrapie brain homogenate and examined the faecal excretion of disease-associated prion protein (PrPTSE) during the course of infection. The intestinal fate of ingested PrPTSE was further investigated by monitoring the deposition of the protein in components of the gut wall using immunohistochemistry and paraffin-embedded tissue (PET) blotting. Western blotting of faecal extracts showed shedding of PrPTSE in the excrement at 24–72 h post infection (hpi), but not at 0–24 hpi or at later preclinical or clinical time points. About 5% of the ingested PrPTSE were excreted via the faeces. However, the bulk of PrPTSE was cleared from the alimentary canal, most probably by degradation, while an indiscernible proportion of the inoculum triggered intestinal infection. Components of the gut-associated lymphoid tissue (GALT) and the enteric nervous system (ENS) showed progressing accumulation of PrPTSE from 30 days post infection (dpi) and 60 dpi, respectively. At the clinical stage of disease, substantial deposits of PrPTSE were found in the GALT in close vicinity to the intestinal lumen. Despite an apparent possibility of shedding from Peyer’s patches that may involve the follicle-associated epithelium (FAE), only small amounts of PrPTSE were detected in faeces from clinically infected animals by serial protein misfolding cyclic amplification (sPMCA). Although excrement may thus provide a vehicle for the release of endogenously formed PrPTSE, intestinal clearance mechanisms seem to partially counteract such a mode of prion dissemination.

Direct Detection of Soil-Bound Prions

Scrapie and chronic wasting disease are contagious prion diseases affecting sheep and cervids, respectively. Studies have indicated that horizontal transmission is important in sustaining these epidemics, and that environmental contamination plays an important role in this. In the perspective of detecting prions in soil samples from the field by more direct methods than animal-based bioassays, we have developed a novel immuno-based approach that visualises in situ the major component (PrPSc) of prions sorbed onto agricultural soil particles. Importantly, the protocol needs no extraction of the protein from soil. Using a cell-based assay of infectivity, we also report that samples of agricultural soil, or quartz sand, acquire prion infectivity after exposure to whole brain homogenates from prion-infected mice. Our data provide further support to the notion that prion-exposed soils retain infectivity, as recently determined in Syrian hamsters intracerebrally or orally challanged with contaminated soils. The cell approach of the potential infectivity of contaminated soil is faster and cheaper than classical animal-based bioassays. Although it suffers from limitations, e.g. it can currently test only a few mouse prion strains, the cell model can nevertheless be applied in its present form to understand how soil composition influences infectivity, and to test prion-inactivating procedures.

DYNAMICS OF PRION DISEASE TRANSMISSION IN MULE DEER

Chronic wasting disease (CWD), a contagious prion disease of the deer family, has the potential to severely harm deer populations and disrupt ecosystems where deer occur in abundance. Consequently, understanding the dynamics of this emerging infectious disease, and particularly the dynamics of its transmission, has emerged as an important challenge for contemporary ecologists and wildlife managers. Although CWD is contagious among deer, the relative importance of pathways for its transmission remains unclear. We developed seven competing models, and then used data from two CWD outbreaks in captive mule deer and model selection to compare them. We found that models portraying indirect transmission through the environment had 3.8 times more support in the data than models representing transmission by direct contact between infected and susceptible deer. Model-averaged estimates of the basic reproductive number (R0) were 1.3 or greater, indicating likely local persistence of CWD in natural populations under conditions resembling those we studied. Our findings demonstrate the apparent importance of indirect, environmental transmission in CWD and the challenges this presents for controlling the disease.

Prion disease: horizontal prion transmission in mule deer.

Epidemics of contagious prion diseases can be perpetuated by horizontal (animal to animal) and maternal (dam to offspring, before or after birth) transmission, but the relative importance of each mechanism is unclear. Here we compare the incidence of chronic wasting disease (CWD) in captive mule deer (Odocoileus hemionus) that is attributable to horizontal or maternal transmission. We find that horizontal transmission is remarkably efficient, producing a high incidence of disease (89%) in a cohort of deer in which maternal transmission was improbable. Our results indicate that horizontal transmission is likely to be important in sustaining CWD epidemics.