Lions&Prions&Deer Table 1. Model selection statistics and hazard ratio estimates for influences of prion infection status (‘‘status’’) and sex on mule deer survival at Table Mesa. Model Status status+sex status+sex+sex*status Sex Model selection AIC 72.98 74.90 76.86 84.70 DAIC 0 1.926 3.882 11.72 L(model|data) 1.0000 0.3817 0.1436 0.0028 wr 0.654 0.25 0.094 0.002 Hazard ratio status 3.84 3.86 4.25 sex 1.106 1.27 1.068 sex*status 0.832 doi:10.1371/journal.pone.0004019.t001 subtle changes in behavior or condition may have been sufficient cues to draw a predator’s attention to infected individuals or increase their vulnerability to attack. Of 131 different deer captured over the 2-year period, 123 were homozygous for serine at codon 225 of their endogenous prion protein (PrP) gene; the remaining eight (6%) were serine- phenylalanine heterozygotes at codon 225. Overall, 31 (25%; 95% binomial CI 18–34%) serine homozygotes were infected when first sampled; similarly, two (25%; 95% binomial CI 3–65%) serine-phenylalanine heterozygotes also were infected when first sampled. Prevalence among the 46 adult male deer we sampled (41%; 95% binomial CI 27–57%) was about twice prevalence among the 69 adult females (20%; 95% binomial CI 12–32%); infections were not detected in any of 16 deer first sampled when they were ,2 years old (Fig. 3). Nearly 80% of the infected deer of both sexes were 2–4 years old (Fig. 3A). Prevalence appeared to vary more across age classes among males than among females (Fig. 3B). Of 65 initially uninfected deer that we sampled in at least two consecutive years (n = 77 deer6years of presumed susceptibility), 19 became infected (estimated incidence = 0.23 new infections per previously uninfected deer per year; 95% binomial CI 0.15–0.34 new infections per previously uninfected deer per year). As reflected in prevalence trends, incidence tended to be higher in male deer (n = 22 previously uninfected deer6years; estimated incidence = 0.36 new infections per previously uninfected deer per year, 95% binomial CI 0.17–0.59 new infections per previously uninfected deer per year) than in females (n = 59 previously uninfected deer6years; estimated incidence = 0.19 new infections per previously uninfected deer per year, 95% binomial CI 0.1– 0.31 new infections per previously uninfected deer per year). Discussion Selectively removing infected individuals from a population should be an effective disease control strategy [7,11–13], but under conditions where predation exacerbates pathogen transmission prevalence can be elevated paradoxically [14–16]. At best, selective predation did not appear to be controlling prion transmission at Table Mesa. Although prion-infected deer were much more likely to be killed by mountain lions than uninfected deer (relative risk = 3.67, 95% CI 1.08–12.45), prevalence and incidence of prion infection were still remarkably high: about one fourth of the adult deer in our sample were infected when first captured, and about one fourth of the susceptible adult deer became infected annually. Observed prevalence was relatively high compared to that previously reported in mule deer populations elsewhere [6,17], but still within the range predicted by a simple model of prion epidemic dynamics [8]. No previous attempts had been made to estimate prevalence or control prion disease in the Table Mesa herd, and this deer population is largely protected from hunting by humans. Consequently, whether our study simply included a period of high prevalence and incidence within the course of a typical epidemic in a mule deer herd or represents an atypical situation cannot be discerned. Regardless, our data show that prion infection in a natural population can surge seemingly unabated even in the face of intense selective predation. If sustained, the combination of high prevalence and low survival among infected individuals portend adversity for a mule deer population. Average adult survival in a prion-infected deer herd can be calculated as sa~ðp|siÞzðð1{pÞ|suÞ, where sa is overall adult deer survival, si is survival of infected deer, su is survival of uninfected deer, and p is prevalence of prion infection. Although survival among uninfected deer approximated the range-wide average for adult mule deer [18], estimated overall adult survival for the Table Mesa deer herd was 0.72. A mule deer population would be expected to decline in the face of such rates [18], and observed trends in deer abundance at Table Mesa appear consistent with these predictions. Based on historical field records and observations, prion disease likely has been occurring in this area since at least 1985, and its emergence over the last two decades or more has coincided with a 45% decline in estimated deer abundance despite ample habitat and protection from hunting by humans (Fig. 1B). In addition to the direct effects of disease on deer survival, the epidemic at Table Mesa could be producing an abundance of vulnerable prey [11,12,19,20], thereby enhancing mountain lion survival and reproduction. Behavioral changes including reduced alertness in the later stages of chronic wasting disease [4,5] should enhance predator success [11,20]. Although local mountain lion abundance has not been estimated, at least eleven individuals resided in or within ,7 km of the Table Mesa area sometime during the course of our study. Whether mountain lion predation somehow reciprocally enhances prion transmission is unknown. However, the tendency for predation to promote social grouping among herbivores [21] could help sustain transmission by maintaining relatively high effective densities [14] even as overall deer abundance declines. One possible outcome of such interplay would be the local depression of deer and concurrent overabun- dance of mountain lions relative to their preferred natural prey. Our findings provide compelling evidence that prion epidemics can affect mule deer population dynamics locally – whether or not native ecosystems dominated by deer species will be altered at larger geographic scales by the emergence of contagious prion disease remains to be determined. PLoS ONE | www.plosone.org 2 December 2008 | Volume 3 | Issue 12 | e4019