Integrative modeling of the spread of serious infectious diseases and corresponding wastewater dynamics.

The COVID-19 pandemic has emphasized the critical need for accurate disease modeling to inform public health interventions. Traditional reliance on confirmed infection data is often hindered by reporting delays and under-reporting, while antigen or antibody testing of a full cohort can be costly and impractical. Wastewater-based surveillance offers a promising alternative by detecting viral concentrations from fecal shedding, potentially providing a more accurate estimate of true infection prevalence. However, challenges remain in optimizing sampling protocols, locations, and normalization strategies, particularly in accounting for environmental factors like precipitation. We present an integrative model that simulates the spread of serious infectious diseases by linking detailed infection dynamics with wastewater processes through viral shedding curves. Through comprehensive simulations, we examine how virus characteristics, precipitation events, measurement protocols, and normalization strategies affect the relationship between infection dynamics and wastewater measurements. Our findings reveal a complex relationship between disease prevalence and corresponding wastewater concentrations, with key variability sources including upstream sampling locations, continuous rainfall, and rapid viral decay. Notably, we find that flow rate normalization can be unreliable when rainwater infiltrates sewer systems. Despite these challenges, our study demonstrates that wastewater-based surveillance data can serve as a leading indicator of disease prevalence, predicting outbreak peaks before they occur. The proposed integrative model can thus be used to optimize wastewater-based surveillance, enhancing its utility for public health monitoring.