Machine Learning and ARIMA Model Averaging for Adaptive Public Health Forecasting: Comparative Evaluation and an Ontario COVID-19 Case Study

Public health forecasts must respond to abrupt changes in surveillance data without over-extrapolating noise, reporting artifacts, or temporary trends. We evaluated autoregressive integrated moving average (ARIMA), random forest, and extreme gradient boosting (XGBoost) models using 190 weekly observations of publicly available Ontario COVID-19 case counts from January 2020 to October 2023. Rolling-origin time-series cross-validation preserved temporal order during model tuning and evaluation. Performance was assessed across three operating dimensions: responsiveness following selected turning points, forecast horizons of one to six weeks, and the amount of historical training data. We also developed Machine Learning and ARIMA Model Averaging (MLAMA), a non-negative performance-weighted ensemble with weights that vary by forecast horizon and responsiveness setting. Retrospective comparisons showed that ARIMA adapted rapidly after turning points but its normalized error increased at longer horizons. Random forest and XGBoost were less responsive initially but maintained more stable normalized error over longer horizons. For two-week forecasts at the end of the study period, training on the most recent data outperformed using longer historical periods, particularly for XGBoost. MLAMA achieved the lowest normalized mean absolute percentage error across most forecast horizons and ranked among the best-performing methods across responsiveness settings. These findings support selecting forecasting models according to operating conditions rather than relying on a single universally preferred approach. MLAMA provides a practical framework for combining complementary statistical and machine-learning forecasts. The accompanying Python package is currently maintained in a private repository while software validation and reproducibility testing are completed.

A Transferable Learned Temporal Prior for Transmission Reconstruction and Decision-Relevant Uncertainty in Real Outbreak Labels

Outbreak transmission reconstruction treats epidemiological timing and transmission labels as deterministic ground truth; neither has been systematically evaluated. We trained a logistic regression temporal prior on eleven disease families, locked all parameters before accessing any target outbreak data, and applied it without refitting to a strict Andes virus (ANDV) parent-ranking benchmark of 29 tasks. The locked prior achieved mean reciprocal rank (MRR) 0.571 versus 0.274 and Top-1 accuracy 37.9% versus 13.8% against the best source-trained parametric baseline (permutation p <= 0.0002; 7-8 reversals to lose MRR significance). A phylogenetic concordance audit of 75 NYC mpox inter-host pairs - independent label-reliability evidence rather than a prior validation - found that 54.67% (exact 95% CI: 42.75-66.21%) were genomically unresolved or unsupported. Retaining uncertain edges in ANDV and Guangdong Delta graphs shifted top-5 source-priority sets (Jaccard 0.429-0.667). Transmission-label uncertainty was measurable in the outbreak evidence modules examined, and retaining uncertain links changed which source cases were prioritized for intervention.

Generating Public Health Responses using Survey-Augmented Large Language Models

Epidemiological models often rely on survey data to represent how individuals make health-related decisions, such as whether to vaccinate or adopt protective behaviors. However, repeated large-scale surveys are costly, time-consuming, and limited in the range of scenarios they can capture. In this work, we investigate whether large language models (LLMs) can generate synthetic survey responses that reproduce patterns observed in real populations. Using longitudinal data from the FluPaths surveys, we first identify groups associated with broadly positive or negative attitudes toward vaccination through clustering analysis. We then evaluate several LLMs using a cluster-informed prompting approach to generate synthetic survey responses across multiple epidemic waves. Across models, the synthetic data generally reproduce the distributions of demographic characteristics, vaccination-related beliefs, risk perceptions, and health behaviors observed in the survey data. However, they are less successful at capturing how these factors vary together within respondents. Some models reproduce group-level vaccination trends more reliably than others, although performance varies across waves. We also trained a classifier to distinguish real from synthetic records and found that the generated responses remained identifiable as synthetic. Overall, our findings suggest that LLM-generated survey data may provide a useful tool for exploratory data augmentation and we hope that it could support agent-based epidemic modeling approaches. However, the generated data should not be treated as a substitute for human survey data without further methodological improvements and validation.

An Infectious Disease Spread Simulation Based on Large Language Model Decision Making

Modelling individual decision-making during infectious disease outbreaks is crucial for understanding behavioural dynamics and informing effective public health interventions. Prior work has shown that large language models can simulate realistic human behaviour by generating agent decisions based on demographic prompts and situational context. We build on this foundation with a spatially grounded, agent-based simulation framework that integrates LLM-generated decisions about self-reported influenza-like illness into a census-based synthetic population of agents. Location is treated as a central feature: agents are assigned to spatial units within cities, capturing the spatial distributions of different demographic groups using real-world census data and enabling geographically diverse behavioural modelling. We implement and compare three decision scenarios, independent reasoning, household influence, and message framing, and simulate self-reporting outcomes in San Francisco and Atlanta. Results reveal that income and education are the dominant drivers of reporting rate variation, with smaller but consistent effects from geography, LLM model choice, and message framing. Our framework generates synthetic data that captures both social and geographic heterogeneity, supporting spatial epidemiological modelling and bias-aware behavioural analysis.

EpiEvolve: Self-Evolving Agents for Streaming Pandemic Forecasting under Regime Shifts

Epidemic LLM forecasters are usually trained and evaluated as static supervised models, whereas operational pandemic forecasting is a streaming process in which labels arrive after predictions and disease regimes shift over time. We study this mismatch in weekly COVID-19 hospitalization trend forecasting across five variant regimes. We introduce EpiEvolve, a self-evolving agent that wraps an LLM forecaster trained on the warm-start period and keeps its weights fixed during streaming. EpiEvolve adapts by storing forecast outcomes in a hierarchical episodic memory, reflecting on delayed labels, retrieving cases relevant to the current regime, and distilling recurring errors into strategic rules. The resulting context lets the forecaster reuse its own past predictions and outcomes in later weeks while following a chronological protocol that prevents future leakage. On the streaming dataset, EpiEvolve reaches $0.629$ average accuracy, compared with $0.561$ for the static backbone and $0.325$ for the external CDC ensemble, and reduces recovery lag after regime shifts from $5$ to $2$ weeks. Ablations show that reflection, strategic memory, and regime-aware retrieval each contribute to the gains.

The Epi-LLM Framework: probing LLM behavioral priors through epidemiological agent-based models

Human behaviour during epidemics affects infectious disease dynamics, but quantifying this remains deeply challenging. Here we introduce the Epi-LLM framework: a novel integration of agent-based modelling, real-life epigames, and large language models (LLMs) in which a synthetic society of agents reasons and adapts dynamically over an outbreak contact network. Comparing synthetic agent behaviour against a no-intervention SEIR baseline and human participant data from the AUIB epigame study, we find that LLM agents across four different architectures reduced peak active infections, with quarantine compliance peaking at 58-65% on day six of the 15-day simulation. A binomial generalised linear model showed that perceived health severity was the strongest predictor of quarantine behaviour ($β= 0.33, p = 0.002$), yielding a pseudo-$R^2$ of 0.055, comparable to the 0.072 observed in the human trial. LLM architecture is a key determinant of epidemic dynamics: low-variance architectures offer greater internal validity for testing behavioural rules, while high-variance models may better represent real-world decision-making. Geographic labels alone do not induce culturally differentiated behaviour; explicit attitudinal parameterisation is required. This proof-of-principle work lays the groundwork for deploying the Epi-LLM framework as a scalable, risk-free simulation environment for pandemic preparedness research.