EpiGuard: An Autonomous Infectious-Disease Early Warning Agent Platform

Probabilistic forecasting of infectious diseases is crucial for public health monitoring and preparedness but has historically relied on labor-intensive manual model curation by expert modeling teams. Bespoke development is an obstacle to scaling models to granular geographic resolutions or emerging pathogens. Here, we prospectively evaluate Empirical Research Assistance (ERA), an autonomous system that uses Large Language Model-guided tree search to iteratively generate, evaluate, and optimize executable forecasting software. ERA was primarily prompted with methodological approaches to implement, while in some instances it was tasked with developing forecasting approaches from scratch. In a fully prospective, real-time evaluation during the 2025-26 United States respiratory season, ERA generated methodologically diverse models for influenza, COVID-19, and respiratory syncytial virus (RSV). Aggregating a selection of these automatically-generated models yielded an ensemble that ranked first overall in official Centers for Disease Control and Prevention (CDC) post-season evaluations and outperformed the gold-standard CDC forecast ensembles across all three pathogens in a real-time prediction challenge. Additionally, ERA successfully navigated data-scarce scenarios for RSV. Controlled retrospective ablations allowed for additional explorations of the impact of optimization target and instruction-following on forecast accuracy. Preliminary experiments indicate that ERA's search optimization metric influences behavior of output forecasts, and using higher-tier language models in-search improves predictive performance. By autonomously generating interpretable code that creates epidemiologically relevant predictions, this framework provides a path toward rapidly scaling high-quality disease forecasting.

Accurate epidemic forecasting is crucial for public health response, resource allocation, and outbreak intervention, but remains difficult with sparse, noisy, and highly non-stationary data. Because epidemics unfold across interacting regions, spatiotemporal methods are natural candidates for improving forecasts. Despite growing interest in spatial information, no standardized benchmark exists, and current evaluations often use simple chronological train-test splits that do not reflect real-time forecasting practice. We address this gap with SpatialEpiBench, a challenging benchmark for spatiotemporal epidemic forecasting in realistic public-health settings. SpatialEpiBench includes 11 epidemic datasets with standardized rolling evaluations and outbreak-specific metrics. We evaluate adjacency-informed forecasting models with widely used epidemic priors that adapt general models to epidemiology, but find that most methods underperform a simple last-value baseline from 1 day to 1 month ahead, even during outbreaks and with these priors. We identify three major failure modes: (1) poor outbreak anticipation, (2) difficulty handling sparsity and noise, and (3) limited utility of common geographic adjacency for epidemiological spatial information. We release benchmark data, code, and instructions at https://github.com/Rachel-Lyu/SpatialEpiBench to support development of operationally useful epidemic forecasting models.

Epidemic forecasting has become an integral part of real-time infectious disease outbreak response. While collaborative ensembles composed of statistical and machine learning models have become the norm for real-time forecasting, standardized benchmark datasets for evaluating such methods are lacking. Further, there is limited understanding on performance of these methods for novel outbreaks with limited historical data. In this paper, we propose IDOBE, a curated collection of epidemiological time series focused on outbreak forecasting. IDOBE compiles from multiple data repositories spanning over a century of surveillance and across U.S. states and global locations. We perform derivative-based segmentation to generate over 10,000 outbreaks covering multiple outcomes such as cases and hospitalizations for 13 diseases. We consider a variety of information-theoretic and distributional measures to quantify the epidemiological diversity of the dataset. Finally, we perform multi-horizon short-term forecasting (1- to 4-week-ahead) through the progression of the outbreak using 11 baseline models and report on their performance. In addition to standard metrics such as NMSE and MAPE for point forecasts, we include probabilistic scoring rules such as Normalized Weighted Interval Score (NWIS) to quantify the performance. We find that MLP-based methods have the most robust performance, with statistical methods having a slight edge during the pre-peak phase. IDOBE dataset along with baselines are released publicly on https://github.com/NSSAC/IDOBE to enable standardized, reproducible benchmarking of outbreak forecasting methods.