Chronic Wasting Disease (CWD) poses a significant challenge to wildlife disease management, driven by the highly infectious nature of prions, the potential for both direct and indirect transmission routes, and the prolonged progression of the disease in infected cervids. These features greatly complicate surveillance and control efforts in both free-ranging and captive cervid populations. Recent advances in Real-Time Quaking-Induced Conversion (RT-QuIC) assays and related technologies are contributing to a paradigm shift in CWD surveillance. Due to its remarkable sensitivity and specificity, RT-QuIC offers the detection of prions in a variety of environmental and biological samples that were previously untestable. Simultaneously, agent-based epidemiological modeling informed by CWD biology and cervid demographics (e.g., OvCWD) offers a valuable framework for designing and optimizing novel RT-QuIC-based surveillance strategies. We present three innovative RT-QuIC testing applications that enhance CWD surveillance: (1) detection of CWD prions in cervid saliva on non-porous surfaces, (2) monitoring prions in environmental matrices such as soil and water near herd congregation sites, and (3) testing of skeletal remains years after deposition. Surveillance data derived from both wild and captive white-tailed deer populations across these three areas are summarized. We show how these three approaches can be used strategically with agent-based epidemiological models to guide efforts to prevent disease spread, identify and remediate environmental prion reservoirs, and ultimately improve the sustainability of cervid populations. Our findings underscore the potential of integrating RT-QuIC surveillance with epidemiological modeling to transform CWD management through proactive, data-driven strategies.
