Intra-host mathematical model of chronic wasting disease dynamics in deer (<i>Odocoileus</i>)

<p>Bioassays of native cervid hosts have established the presence of infectious chronic wasting disease (CWD) prions in saliva, blood, urine, and feces of clinically diseased and pre-clinical infected deer. The intra-host trafficking of prions from the time of initial infection to shedding has been less well defined. We created a discrete-time compartmentalized model to simulate the misfolding catalysis, trafficking, and shedding of infectious prions throughout the organ systems of CWD-infected cervids. Using parameter values derived from experimental infections of North American deer (<i>Odocoileus spp</i>.), the exponential-based model predicts prion deposition over time with: 1) nervous tissues containing the highest deposition of prions at 20 months post-infection and 2) excreted fluids containing low levels of prions throughout infection with the highest numbers of prions predicted to be shed in saliva and feces (as high as 10 lethal doses (1.34 × 10²⁹ prions) in 11–15 months). These findings are comparable to prion deposition described in literature as assayed by conventional and ultrasensitive amplification assays. The comparison of our model to published data suggests that highly sensitive assays (sPMCA, RT-QuIC, and bioassay) are appropriate for early prion detection in bodily fluids and secretions. The model provides a view of intra-host prion catalysis leading to pre-clinical shedding and provides a framework for continued development of antemortem diagnostic methods.</p

Reimmunization increases contraceptive effectiveness of gonadotropin-releasing hormone vaccine (GonaCon-Equine) in free-ranging horses (<i>Equus caballus</i>): Limitations and side effects

<div><p>Wildlife and humans are increasingly competing for resources worldwide, and a diverse, innovative, and effective set of management tools is needed. Controlling abundance of wildlife species that are simultaneously protected, abundant, competitive for resources, and in conflict with some stakeholders but beloved by others, is a daunting challenge. Free-ranging horses (<i>Equus caballus</i>) present such a conundrum and managers struggle for effective tools for regulating their abundance. Controlling reproduction of female horses presents a potential alternative. During 2009–2017, we determined the long-term effectiveness of GnRH vaccine (GonaCon-Equine) both as a single immunization and subsequent reimmunization on reproduction and side effects in free-ranging horses. At a scheduled management roundup in 2009, we randomly assigned 57 adult mares to either a GonaCon-Equine treatment group (<i>n</i> = 29) or a saline control group (<i>n</i> = 28). In a second roundup in 2013, we administered a booster vaccination to these same mares. We used annual ground observations to estimate foaling proportions, social behaviors, body condition, and injection site reactions. We found this vaccine to be safe for pregnant females and neonates, with no overt deleterious behavioral side effects during the breeding season. The proportion of treated mares that foaled following a single vaccination was lower than that for control mares for the second (<i>P =</i> 0.03) and third (<i>P</i> = 0.08) post-treatment foaling seasons but was similar (<i>P</i> = 0.67) to untreated mares for the fourth season, demonstrating reversibility of the primary vaccine treatment. After two vaccinations, however, the proportion of females giving birth was lower (<i>P</i> <0.001) than that for control mares for three consecutive years and ranged from 0.0–0.16. The only detectable adverse side effect of vaccination was intramuscular swelling at the vaccination site. Regardless of vaccine treatment (primary/secondary), approximately 62% (34/55) of immunized mares revealed a visible reaction at the vaccine injection site. However, none of these mares displayed any evidence of lameness, altered gait or abnormal range of movement throughout the 8 years they were observed in this study. Our research suggests that practical application of this vaccine in feral horses will require an initial inoculation that may provide only modest suppression of fertility followed by reimmunization that together could result in greater reduction in population growth rates over time.</p></div

Comparative relative risk reduction (RRR), 95% confidence intervals, and p-values associated with differences in foaling proportions between GonaCon-treated and control mares during 2009–2017.

<p>Comparative relative risk reduction (RRR), 95% confidence intervals, and p-values associated with differences in foaling proportions between GonaCon-treated and control mares during 2009–2017.</p

Comparative probability of foaling and pregnancy for treatment and control groups of free-ranging feral horses (<i>Equus caballus)</i> mares selected for this experiment.

<p>Mares were treated with a primary vaccination of GonaCon-Equine in October 2009 and then reimmunized with the same vaccine in September 2013 at scheduled gathers at Theodore Roosevelt National Park, North Dakota, USA. GonaCon vaccinations occurred at the time points represented by the red arrows. Symbols correspond to observed p-values for relative risk comparisons between treatment groups within years (p-value between 0.05 and 0.1 = +, for < 0.05 = x, and for < 1x10^-05 = *).</p