Spatial Epidemic Modeling

Accurate medium- to long-range epidemic forecasting requires extrapolating high-dimensional, heterogeneous and nonstationary dynamics from partial observations. Yet hybrid models often leave implicit which observations inform which epidemic processes and how learned graph interactions modify system state. We introduce LE-EpiGNODE, which replaces generic message passing with process-specific, mechanism-guided neural operators: age-contact information drives Lagrangian infection generation, whereas mobility drives conservative Eulerian population transport within a structure-preserving universal differential equation. We evaluated LE-EpiGNODE across 14 controlled synthetic mechanisms spanning time-modulated, state-dependent, nonlinear and coupled dynamics, three complementary COVID-19 settings, 21 comparator models and five targeted ablations. Forecasting gains tended to become more pronounced at longer horizons; at the longest horizon, LE-EpiGNODE achieved the lowest WMAPE in all three real-world datasets, reducing error by 17.7-40.0% relative to the best baseline. Controlled ablations linked these gains to the Lagrangian-Eulerian decomposition and process-aligned priors, while synthetic ground truth showed that learned operators and induced state fluxes track known generating dynamics. These results support mechanism-organized graph neural dynamics as a route to reliable long-horizon extrapolation with directly testable, process-level mechanistic interpretation beyond trajectory accuracy.

Compartment models of infectious diseases are often linear in coefficients that are physical parameters or products or ratios of them. We exploit this with closed-form least squares and equip the estimates with distribution-free uncertainty. Physics-informed regression (PIR) fits the parameters to finite-difference derivatives of the data; we introduce physics-informed weak regression (PIWR), which integrates the model in time instead, needs no derivatives of the data, estimates the initial state jointly and is high-order accurate. To quantify uncertainty we wrap both estimators in split conformal prediction, with a calibration population generated by the physics-based model itself, giving simultaneous intervals for all parameters with a finite-sample coverage guarantee. A residual-adaptive factor, computed without ground truth, scales the intervals to each data set (PIWR-RACC). On the eleven benchmark models of disease-informed neural networks (DINNs), PIWR or PIR-FD6 is one to four orders of magnitude more accurate than the reported DINN results wherever the sampling resolves the dynamics, in about a millisecond per fit instead of minutes to hours of training, and the 90% intervals achieve 87-92% coverage in all 88 settings. On the S3I3R model of the original PIR study, PIWR lowers the reported PIR errors by about three orders of magnitude. On real data from the 1978 boarding-school influenza outbreak, a variable-projection variant gives calibrated 95% intervals that overlap those of a Bayesian analysis. On a time-varying transmission benchmark, a B-spline expansion of beta(t) keeps PIR and PIWR linear; they are more accurate than physics-informed neural networks in three of four cases and comparable in the noisiest, with simultaneous bands for beta(t). The complete conformal calibration takes less than two minutes for every benchmark.

Epidemic policy planning often requires coordination between geographical regions, taking into account mobility-driven spillovers and how to make use of limited resources. Existing methods either lack action-conditioned models of coupled dynamics or cannot guarantee per-period feasibility. We present EpiMind, a graph world model framework for constrained epidemic policy planning across regions. A graph-factored recurrent state-space model generates joint policy-conditioned rollouts from regional latent beliefs, while graph-temporal ADMM optimizes regional interventions, enforces shared-resource feasibility through projection, and evaluates temporal specifications under the learned model. EpiMind reduces admission RMSE by 29% relative to graph-free dynamics modeling, plans within 1-5% of the best feasible constant policy with guaranteed shared-budget feasibility, and outperforms all deployable baselines across three resource budgets in real-context evaluation. These results demonstrate that graph-structured policy imagination with explicit constrained coordination supports effective epidemic interventions from learned dynamics.

Mass gathering events like concerts, sports matches, and festivals bring many people into close contact within a short period, creating localized bursts of infection that can shape epidemic outcomes across an entire city. To evaluate how these transient transmission events translate into broader urban impacts, we developed a simulation model linking event-scale contact dynamics with citywide commuting networks. Using Madrid, Spain, as a case study, we compared several types of gatherings and examined how their effects changed under different levels of disease transmissibility. We found that mass gatherings consistently amplified outbreak magnitude, accelerated progression, advanced district-level arrival times, and synchronized spatial spread. Remarkably, while the initial seed size generated at the event accounted for much of this acceleration, post-event transmission conditions provided complementary predictive signal regarding invasion timing. These findings demonstrate that mitigating transmission during mass gatherings can yield downstream public health benefits by delaying broader spatial spread. More generally, this multiscale framework offers a tool to evaluate how temporary, localized contact shifts produce longer-lasting consequences for urban populations.

Artificial Intelligence agents based on large language models provide convenient natural language interfaces to scientific software, but reliability is not automatic. Here we introduce the Epydemix Agent Framework, an additive layer over Epydemix, an open-source Python library for stochastic compartmental epidemic modeling. The framework extends the library with four capabilities to facilitate interaction with an AI agent: discovery of available models and parameters, preventive validation of a declarative scenario specification, execution through tested library code, and inspectability of results. These capabilities let an agent handle the entire modeling process, from the natural-language description of the scenario to quantitative results, figures, and interpretation of findings without writing custom code. Each step reads input files and saves results in a separate output bundle, making the process auditable and reproducible. First, we show the end-to-end workflow with a case study comparing vaccination strategies for a novel respiratory virus. Second, we assessed the framework across 50 agent sessions and five modeling tasks by comparing the agent use of the framework against the direct use of the Python interface. The framework reduced turns, output tokens, and cost on most tasks, unless it trades resources for per-point reproducibility.

Disease spread represents an increasing challenge in refugee and internally displaced person (IDP) settlements. The movement and interaction of people within camps is influenced by their layout, which therefore has the potential to significantly affect disease spread. This work aims at creating a methodology to explore the potential effects of different camp layouts as mitigating factors in the spread of diseases within settlements. We showcase proof-of-concept experiments by leveraging the JUNE agent-based epidemic model, discuss the kind of operational insights this methodology can facilitate, and provide a framework for future investigations.

As generative AI gains traction, researchers are investigating its potential to serve as proxies for humans. From undergoing cognitive psychology experiments to experiencing an epidemic, generative agents, agents powered by generative AI models, produce realistic human behavior when prompted. This study explores the sensitivity of these generative agents' behavior to prompt modifications and varied persona names of the agents. To assess this sensitivity, we use a generative agent epidemic model, wherein each agent is prompted daily on whether it wants to isolate or commingle with other agents. We found that using synonymous prompts results in negligible changes to the model's outcomes. However, minor variations in prompts, as well as contextual changes, do influence the model's results. Lastly, our data indicates that different persona names assigned to generative agents, specifically those imbued with personas, do not significantly impact epidemic outcomes.

Regional surveillance data reflect local transmission, reporting, seeding, and external infection pressure, which are difficult to identify separately. We introduce GeoID-PINN, a physics-informed neural network (PINN) for susceptible-infectious-recovered-deceased (SIRD) dynamics. The model represents spatial dependence with a row-stochastic source-composition matrix whose rows assign nonnegative source weights that sum to one. We regularize this matrix toward a spatial prior constructed from distance, adjacency, commuting, or lead-lag information. In a four-region simulation with known truth, a compatible distance prior gives source-composition error 0.099. The error rises to 0.159 without regularization and 0.577 under a strongly misspecified prior, while trajectory fit and transmission-scale estimates remain similar. Accurate trajectories therefore do not guarantee recovery of the regional dependence structure. We also evaluate GeoID-PINN retrospectively using COVID-19 data from 64 Louisiana counties. Relative to an autoregressive negative-binomial baseline, Forecast-Trained Geo-PINN reduces mean squared error (MSE) from 32,957 to 11,468 and mean absolute error (MAE) from 70.60 to 57.73. The baseline has lower negative log likelihood (NLL), 5.158 versus 5.346, indicating better distributional fit but worse point accuracy. In a controlled 15-county comparison, county adjacency reduces MSE by 6.85 percent and MAE by 3.1 percent. Similar performance across plausible priors supports structured regularization but not unique edge recovery. These results require prior-sensitivity and observation-model checks before interpretation.

Epidemic forecasting models typically rely on surveillance data reported over administrative regions, treating them as atomic units, thereby obscuring sub-regional spatial structure that shapes disease dynamics. We introduce a spatially structured multimodal epidemic forecasting setting that integrates region-level temporal surveillance data with spatially localized auxiliary signals that are misaligned in resolution and structure, reflecting realistic public health reporting constraints. Building on this formulation, we propose M-SPICE (Multimodal SPatIal Context for Epidemic Forecasting), a structure-aware spatiotemporal forecasting framework that performs joint reasoning over temporal disease dynamics and spatial context via attention-based multimodal fusion, allowing spatial signals to selectively condition temporal representations across forecast horizons. We evaluate our approach on real-world COVID-19, influenza, and influenza-like illness (ILI) forecasting tasks under realistic real-time evaluation protocols. Across all forecasting settings, our method consistently outperforms state-of-the-art multivariate time-series, multimodal, and epidemiological forecasting baselines while maintaining strong probabilistic forecasting performance. Finally, interpretability analyses reveal when, where, and how spatial signals are leveraged, highlighting settings in which purely temporal, region-aggregated models are most likely to fail.

Deep learning has enabled significant advances in time-series causal inference, yet progress remains constrained by the lack of realistic benchmarks with observable counterfactual outcomes. Existing datasets either rely on real-world observations without ground-truth counterfactuals or on simplified simulations that fail to capture complex causal dynamics. To address this gap, we develop a large-scale benchmark for counterfactual prediction in epidemic time series under dynamic interventions. Unlike existing benchmarks, it supports static and time-varying treatments, as well as both single-policy and multi-policy intervention settings, enabling evaluation of causal inference methods across a broad range of causal inference scenarios. Leveraging a calibrated agent-based model grounded in real-world demographic, mobility, epidemiological, and policy data, we generate realistic counterfactual trajectories across more than 150 U.S. counties. Using this benchmark, we evaluate widely used and state-of-the-art causal inference methods, revealing substantial performance differences and highlighting the challenges of realistic time-series causal reasoning.

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.

Spatio-temporal graph-based models have typically been used to forecast new cases of infectious diseases such as COVID-19 and chickenpox outbreaks. However, the use of stochastic modelling into their learning process has been surprisingly under-investigated and rarely considered entire data sets of large countries. As a result, it is unknown whether these models would provide accurate forecasts in real-world disease spread scenarios. In this work, we propose a spatio-temporal stochastic graph-based architecture that integrates a stochastic formulation and uncertainty approximation process to forecast new infectious disease cases. We find that our approach can adapt to encode large and small population geographical networks within a single model architecture. Using two real-world data sets, COVID-19 in the US and chickenpox in Hungary, we report an enhanced effect of the proposed architecture across predictions of the 2022 first wave for COVID-19 in the US and comparative results of chickenpox waves during 2012-2014 in Hungary. By benchmarking with four spatio-temporal graph-based models, quantitative results show competitive overall weekly performance of the proposed approach on forecasting new cases for all 3,218 US counties and all 20 Hungary counties. The proposed approach can represent overall epidemic progression relative to baselines, though with a one-step delay; while exhibiting a reduced sensitivity to high-frequency and low-amplitude variability.

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.

Accurate and reliable forecasting of epidemic incidences is critical for public health preparedness, yet it remains a challenging task due to complex nonlinear temporal dependencies and heterogeneous spatial interactions. Often, point forecasts generated by spatiotemporal models are unreliable in assigning uncertainty to future epidemic events. Probabilistic forecasting of epidemics is therefore crucial for providing the best or worst-case scenarios rather than a simple, often inaccurate, point estimate. We present deep spatiotemporal engression methods to generate accurate and reliable probabilistic forecasts on low-frequency epidemic datasets. The proposed methods act as distributional lenses, and out-of-sample probabilistic forecasts are generated by sampling from the trained models. Our frameworks encapsulate lightweight deep generative architectures, wherein uncertainty is quantified endogenously, driven by a pre-additive noise component during model construction. We establish geometric ergodicity and asymptotic stationarity of the spatiotemporal engression processes under mild assumptions on the network weights and pre-additive noise process. Comprehensive evaluations across six epidemiological datasets over three forecast horizons demonstrate that the proposal consistently outperforms several temporal and spatiotemporal benchmarks in both point and probabilistic forecasting. Additionally, we explore the explainability of the proposal to enhance the models' practical application for informed, timely public health interventions.

Metapopulation epidemic models are a valuable tool for studying large-scale outbreaks. With the limited availability of epidemic tracing data, it is challenging to infer the essential constituents of these models, namely, the epidemic parameters and the relevant mobility network between subpopulations. Either one of these constituents can be estimated while assuming the other; however, the problem of their joint inference has not yet been solved. Here, we propose two encoder-decoder deep learning architectures that infer metapopulation mobility graphs from time-series data, with and without the assumption of epidemic model parameters. Evaluation across diverse random and empirical mobility networks shows that the proposed approach outperforms the state-of-the-art topology inference. Further, we show that topology inference improves dramatically with data on additional pathogens. Our study establishes a robust framework for simultaneously inferring epidemic parameters and topology, addressing a persistent gap in modeling disease propagation.

Spatio-temporal epidemic forecasting is critical for public health management, yet existing methods often struggle with insensitivity to weak epidemic signals, over-simplified spatial relations, and unstable parameter estimation. To address these challenges, we propose the Spatio-Temporal priOr-aware Epidemic Predictor (STOEP), a novel hybrid framework that integrates implicit spatio-temporal priors and explicit expert priors. STOEP consists of three key components: (1) Case-aware Adjacency Learning (CAL), which dynamically adjusts mobility-based regional dependencies using historical infection patterns; (2) Space-informed Parameter Estimating (SPE), which employs learnable spatial priors to amplify weak epidemic signals; and (3) Filter-based Mechanistic Forecasting (FMF), which uses an expert-guided adaptive thresholding strategy to regularize epidemic parameters. Extensive experiments on real-world COVID-19 and influenza datasets demonstrate that STOEP outperforms the best baseline by 11.1% in RMSE. The system has been deployed at a provincial CDC in China to facilitate downstream applications.

This paper presents a hybrid modeling approach that couples an Agent-Based Model (ABM) with a partial differential equation (PDE) model in an epidemic setting to simulate the spatial spread of infectious diseases using a compartmental structure with seven health states. The goal is to reduce the computational complexity of a full-ABM by introducing a coupled ABM-PDE model that offers significantly faster simulations while maintaining comparable accuracy. Our results demonstrate that the hybrid model not only reduces the overall simulation runtime (defined as the number of runs required for stable results multiplied by the duration of a single run) but also achieves smaller errors across both 25% and 100% population samples. The coupling mechanism ensures consistency at the model interface: agents crossing from the ABM into the PDE domain are removed and represented as density contributions, while surplus density in the PDE domain is used to generate agents with plausible trajectories derived from mobile phone data. We evaluate the hybrid model using real-world mobility and infection data for the Berlin-Brandenburg region in Germany, showing that it captures the core epidemiological dynamics while enabling efficient large-scale simulations. These results demonstrate that the proposed ABM-PDE framework provides a robust and computationally efficient alternative to full-scale agent-based simulations, making it suitable for realistic epidemic modeling and scenario analysis.