Modeling the Emergence Cascade: From Wildlife Pathogen Circulation to Human Outbreak Amplification

PROJECT SUMMARY/ABSTRACT Emerging infectious diseases are among the greatest threats to global health, as shown by recent emergences of Ebola, Zika, avian influenza, and coronaviruses. Although zoonotic outbreaks are recognized as a One Health challenge, most research has focused on single pathogens, retrospective studies of animal hosts, or on human-centered transmission dynamics. This siloed approach neglects how upstream drivers such as wildlife epizootics and hidden host- specific zoonotic burdens influence spillover risk, as well as the ecological and social conditions that transform small spillover events into large epidemics. Without an integrated framework linking animal and human health, pandemic preparedness remains largely reactive rather than preventive. My proposed R35 MIRA program will develop a comprehensive, predictive framework for zoonotic emergence spanning the full cascade from wildlife epizootics to human spillover and outbreak amplification. My hypothesis is that explicitly incorporating animal health measures into models of human disease risk will significantly improve forecasts. To test this, my team and I will integrate large-scale host-virus networks, ecological and demographic data, and advanced statistical and machine learning approaches. We will: (1) identify ecological and environmental drivers of wildlife epizootics, (2) estimate hidden or unsampled viral burdens as well as true total zoonotic burden across animal host taxa, and (3) quantify spillover and amplification risk through a novel standardized epidemic potential parameter that extends beyond R₀. Results will be synthesized into agent-based models, predictive risk maps and early- warning tools validated with influenza and coronavirus datasets. By explicitly linking animal epizootics, host zoonotic burden, spillover dynamics, and amplification risk, this program will generate a multi-stage, data-driven framework for pathogen emergence. Expected outcomes include transformative insights into the upstream drivers of diseases, identification of early warning signals in wildlife health and actionable forecasting tools to strengthen One Health surveillance efforts and pandemic preparedness. Beyond scientific impact, this program will also establish generalizable methodologies and train researchers in advanced modeling, which aligns with the NIGMS MIRA mission to support sustained, flexible, and impactful research with broad relevance to human health.