Intra-host mathematical model of chronic wasting disease dynamics in deer (Odocoileus)

Abstract

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 (Odocoileus spp.), 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.

The ecology of chronic wasting disease in wildlife

“…Western Blotting, ELISA, and IHC, however, fail to identify low levels of PrP Sc , which are likely present in animals recently exposed to CWD. On the other hand, PMCA and RT-QuIC show higher (ultra) sensitivity of detection than IHC, ELISA, or WB methods (Haley et al, 2009;Holcomb, Galloway & Mathiason, 2016). PMCA and RT-QuIC rely on the amplification of PrP Sc using the same principle by which prions propagate during the disease.…”