How (Not) to Hybridize Neural and Mechanistic Models for Epidemiological Forecasting

Epidemic forecasting faces a fundamental challenge: human behavior dynamically responds to disease spread, creating feedback loops that induce distribution shifts at policy intervention points. This renders data-driven models unreliable under distribution shift. We propose \textbf{SL-BiLEM} (Structured Learnable Behavior-in-the-Loop Epidemic Model), leveraging physical constraints as regularization for robust extrapolation. The framework decomposes effective transmission as $β_{\text{eff}}(t,g) = β_0(g) \times m_{\text{policy}}(t) \times m_{\text{media}}(t) \times m_{\text{comp}}(t,g)$, where monotonicity, smoothness, and bounded-jump constraints on the learned compliance function maintain predictive validity under novel policy regimes. Beyond forecasting, SL-BiLEM enables counterfactual analysis for intervention decision support. We validate forecasting on three real-world datasets (cruise ship, school influenza, and school-district COVID-19 surveillance) and evaluate counterfactual recovery on synthetic benchmarks with known ground truth. SL-BiLEM demonstrates: (1) 76% improvement over neural-mechanistic baselines, with only 53% OOD degradation versus 1142% for neural baselines under policy-induced shift; (2) 100% bootstrap CI coverage across 27 synthetic counterfactual experiments; and (3) Treatment Effect Accuracy exceeding 0.85. These results establish SL-BiLEM as an interpretable tool for public health decision-makers seeking accurate prediction and principled intervention planning.

Accurate multi-week dengue forecasting supports timely vector-control interventions, outbreak preparedness, and healthcare resource allocation. However, newly established surveillance systems often lack the historical data needed to train reliable neural forecasting models. Although pretrained time-series models offer promising zero-shot forecasts, their cross-domain training may not capture local epidemiological dynamics. We propose TREA-Net, a Transferable Residual Epidemiological Adaptation Network for dengue forecasting under limited data. TREA-Net augments neural forecasting backbones with projections from an Environmental Time-Series Susceptible-Infected-Recovered model and learns a lightweight gated residual correction transferable from data-rich to data-scarce regions. Its node-invariant design accommodates surveillance systems with different numbers of locations, while target adaptation requires learning only two global parameters. We transfer knowledge from long-running dengue surveillance in Colombia and Nicaragua to 8-week-ahead forecasting in Mexico and Malaysia using only 78 or 104 weeks of target data. Across five neural backbones and ten transfer settings, TREA-Net improves the corresponding backbone in 9 out of 10 settings, with statistically significant gains. When integrated with TiRex, a foundation model for forecasting, it achieves the lowest mean absolute error across all target datasets. Conformal prediction further maintains empirical coverage while reducing 8-week prediction-interval width by 29.6% in Mexico. These results demonstrate TREA-Net's potential as a lightweight and portable early-warning framework for health agencies with limited surveillance data.

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.