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Environmental transmission is a critical driver of cholera dynamics and a key factor influencing model-based inference and forecasting. This study focuses on stable parameter estimation and forecasting of cholera outbreaks using a compartmental SIRB model informed by three formulations of the environmental transmission rate: (1) a pre-parameterized periodic function, (2) a temperature-driven function, and (3) a flexible, data-driven time-dependent function. We apply these methods to the 1991–1997 cholera epidemic in Peru, estimating key parameters; these include the case reporting rate and human-to-human transmission rate. We assess practical identifiability via parametric bootstrapping and compare the performance of each transmission formulation in fitting epidemic data and forecasting short-term incidence. Our results demonstrate that while the data-driven approach achieves superior in-sample fit, the temperature-dependent model offers better forecasting performance due to its ability to incorporate seasonal trends. The study highlights trade-offs between model flexibility and parameter identifiability and provides a framework for evaluating cholera transmission models under data limitations. These insights can inform public health strategies for outbreak preparedness and response. 

The integration of viral genomic data into public health surveillance has revolutionized our ability to track and forecast infectious disease dynamics. This review addresses two critical aspects of infectious disease forecasting and monitoring: the methodological workflow for epidemic forecasting and the transformative role of molecular surveillance. We first present a detailed approach for validating epidemic models, emphasizing an iterative workflow that utilizes ordinary differential equation (ODE)-based models to investigate and forecast disease dynamics. We recommend a more structured approach to model validation, systematically addressing key stages such as model calibration, assessment of structural and practical parameter identifiability, and effective uncertainty propagation in forecasts. Furthermore, we underscore the importance of incorporating multiple data streams by applying both simulated and real epidemiological data from the COVID-19 pandemic to produce more reliable forecasts with quantified uncertainty. Additionally, we emphasize the pivotal role of viral genomic data in tracking transmission dynamics and pathogen evolution. By leveraging advanced computational tools such as Bayesian phylogenetics and phylodynamics, researchers can more accurately estimate transmission clusters and reconstruct outbreak histories, thereby improving data-driven modeling and forecasting and informing targeted public health interventions. Finally, we discuss the transformative potential of integrating molecular epidemiology with mathematical modeling to complement and enhance epidemic forecasting and optimize public health strategies. 

Phenomenological models are highly effective tools for forecasting disease dynamics using real-world data, particularly in scenarios where detailed knowledge of disease mechanisms is limited. However, their reliability depends on the model parameters’ structural and practical identifiability. In this study, we systematically analyze the identifiability of six commonly used growth models in epidemiology: the generalized growth model (GGM), the generalized logistic model (GLM), the Richards model, the generalized Richards model (GRM), the Gompertz model, and a modified SEIR model with inhomogeneous mixing. To address challenges posed by non-integer power exponents in these models, we reformulate them by introducing additional state variables. This enables rigorous structural identifiability analysis using the StructuralIdentifiability.jl package in JULIA. We validated the structural identifiability results by performing parameter estimation and forecasting using the GrowthPredict MATLAB Toolbox. This toolbox is designed to fit and forecast time series trajectories based on phenomenological growth models. We applied it to three epidemiological datasets: weekly incidence data for monkeypox, COVID-19, and Ebola. Additionally, we assessed practical identifiability through Monte Carlo simulations to evaluate parameter estimation robustness under varying levels of observational noise. Our results confirm that all six models are structurally identifiable under the proposed reformulation. Furthermore, practical identifiability analyses demonstrate that parameter estimates remain robust across different noise levels, though sensitivity varies by model and dataset. These findings provide critical insights into the strengths and limitations of phenomenological models to characterize epidemic trajectories, emphasizing their adaptability to real-world challenges and their role in informing public health interventions. 

Abstract The emergence of viral variants with altered phenotypes is a public health challenge underscoring the need for advanced evolutionary forecasting methods. Given extensive epistatic interactions within viral genomes and known viral evolutionary history, efficient genomic surveillance necessitates early detection of emerging viral haplotypes rather than commonly targeted single mutations. Haplotype inference, however, is a significantly more challenging problem precluding the use of traditional approaches. Here, using SARS-CoV-2 evolutionary dynamics as a case study, we show that emerging haplotypes with altered transmissibility can be linked to dense communities in coordinated substitution networks, which become discernible significantly earlier than the haplotypes become prevalent. From these insights, we develop a computational framework for inference of viral variants and validate it by successful early detection of known SARS-CoV-2 strains. Our methodology offers greater scalability than phylogenetic lineage tracing and can be applied to any rapidly evolving pathogen with adequate genomic surveillance data. 

The 2022–2023 mpox outbreak exhibited an uneven global distribution. While countries such as the UK, Brazil, and the USA were most heavily affected in 2022, many Asian countries, specifically China, Japan, South Korea, and Thailand, experienced the outbreak later, in 2023, with significantly fewer reported cases relative to their populations. This variation in timing and scale distinguishes the outbreaks in these Asian countries from those in the first wave. This study evaluates the predictability of mpox outbreaks with smaller case counts in Asian countries using popular epidemic forecasting methods, including the ARIMA, Prophet, GLM, GAM, n-Sub-epidemic, and Sub-epidemic Wave frameworks. Despite the fact that the ARIMA and GAM models performed well for certain countries and prediction windows, their results were generally inconsistent and highly dependent on the country, i.e., the dataset, as well as the prediction interval length. In contrast, n-Sub-epidemic Ensembles demonstrated more reliable and robust performance across different datasets and predictions, indicating the effectiveness of this model on small datasets and its utility in the early stages of future pandemics. 

Abstract BackgroundDynamical mathematical models defined by a system of differential equations are typically not easily accessible to non-experts. However, forecasts based on these types of models can help gain insights into the mechanisms driving the process and may outcompete simpler phenomenological growth models. Here we introduce a friendly toolbox,SpatialWavePredict, to characterize and forecast the spatial wave sub-epidemic model, which captures diverse wave dynamics by aggregating multiple asynchronous growth processes and has outperformed simpler phenomenological growth models in short-term forecasts of various infectious diseases outbreaks including SARS, Ebola, and the early waves of the COVID-19 pandemic in the US. ResultsThis tutorial-based primer introduces and illustrates a user-friendly MATLAB toolbox for fitting and forecasting time-series trajectories using an ensemble spatial wave sub-epidemic model based on ordinary differential equations. Scientists, policymakers, and students can use the toolbox to conduct real-time short-term forecasts. The five-parameter epidemic wave model in the toolbox aggregates linked overlapping sub-epidemics and captures a rich spectrum of epidemic wave dynamics, including oscillatory wave behavior and plateaus. An ensemble strategy aims to improve forecasting performance by combining the resulting top-ranked models. The toolbox provides a tutorial for forecasting time-series trajectories, including the full uncertainty distribution derived through parametric bootstrapping, which is needed to construct prediction intervals and evaluate their accuracy. Functions are available to assess forecasting performance, estimation methods, error structures in the data, and forecasting horizons. The toolbox also includes functions to quantify forecasting performance using metrics that evaluate point and distributional forecasts, including the weighted interval score. ConclusionsWe have developed the first comprehensive toolbox to characterize and forecast time-series data using an ensemble spatial wave sub-epidemic wave model. As an epidemic situation or contagion occurs, the tools presented in this tutorial can facilitate policymakers to guide the implementation of containment strategies and assess the impact of control interventions. We demonstrate the functionality of the toolbox with examples, including a tutorial video, and is illustrated using daily data on the COVID-19 pandemic in the USA. 

Abstract Quick and accurate forecasts of incidence and mortality trends for the near future are particularly useful for the immediate allocation of available public health resources, as well as for understanding the long-term course of the pandemic. The surveillance data used for predictions, however, may come with some reporting delays. Consequently, auxiliary data sources that are available immediately can provide valuable additional information for recent time periods for which surveillance data have not yet become fully available. In this work, a set of Google search queries by individual users related to COVID-19 incidence and mortality is collected and analyzed. The information from these queries aims to improve quick forecasts. Initially, the identified search query keywords were ranked according to their predictive abilities with reported incidence and mortality. After that, the ARIMA, Prophet, and XGBoost models were fitted to generate forecasts using only the available reported incidence and mortality (baseline model) or together with combinations of searched keywords identified based on their predictive abilities (predictors model). In summary, the inclusion of top-ranked keywords as predictors significantly enhanced prediction accuracy for the majority of scenarios in the range from 50% to 90% across all considered models and is recommended for future use. The inclusion of low-ranked keywords did not provide such an improvement. In general, the ranking of predictors and the corresponding forecast improvements were more pronounced for incidence, while the results were less pronounced for mortality. 

Abstract Simple dynamic modeling tools can help generate real-time short-term forecasts with quantified uncertainty of the trajectory of diverse growth processes unfolding in nature and society, including disease outbreaks. An easy-to-use and flexible toolbox for this purpose is lacking. This tutorial-based primer introduces and illustratesGrowthPredict, a user-friendly MATLAB toolbox for fitting and forecasting time-series trajectories using phenomenological dynamic growth models based on ordinary differential equations. This toolbox is accessible to a broad audience, including students training in mathematical biology, applied statistics, and infectious disease modeling, as well as researchers and policymakers who need to conduct short-term forecasts in real-time. The models included in the toolbox capture exponential and sub-exponential growth patterns that typically follow a rising pattern followed by a decline phase, a common feature of contagion processes. Models include the 1-parameter exponential growth model and the 2-parameter generalized-growth model, which have proven useful in characterizing and forecasting the ascending phase of epidemic outbreaks. It also includes the 2-parameter Gompertz model, the 3-parameter generalized logistic-growth model, and the 3-parameter Richards model, which have demonstrated competitive performance in forecasting single peak outbreaks. We provide detailed guidance on forecasting time-series trajectories and available software (https://github.com/gchowell/forecasting_growthmodels), including the full uncertainty distribution derived through parametric bootstrapping, which is needed to construct prediction intervals and evaluate their accuracy. Functions are available to assess forecasting performance across different models, estimation methods, error structures in the data, and forecasting horizons. The toolbox also includes functions to quantify forecasting performance using metrics that evaluate point and distributional forecasts, including the weighted interval score. This tutorial and toolbox can be broadly applied to characterizing and forecasting time-series data using simple phenomenological growth models. As a contagion process takes off, the tools presented in this tutorial can help create forecasts to guide policy regarding implementing control strategies and assess the impact of interventions. The toolbox functionality is demonstrated through various examples, including a tutorial video, and the examples use publicly available data on the monkeypox (mpox) epidemic in the USA. 

During the 2022–2023 unprecedented mpox epidemic, near real-time short-term forecasts of the epidemic’s trajectory were essential in intervention implementation and guiding policy. However, as case levels have significantly decreased, evaluating model performance is vital to advancing the field of epidemic forecasting. Using laboratory-confirmed mpox case data from the Centers for Disease Control and Prevention and Our World in Data teams, we generated retrospective sequential weekly forecasts for Brazil, Canada, France, Germany, Spain, the United Kingdom, the United States and at the global scale using an auto-regressive integrated moving average (ARIMA) model, generalized additive model, simple linear regression, Facebook’s Prophet model, as well as the sub-epidemic wave andn-sub-epidemic modelling frameworks. We assessed forecast performance using average mean squared error, mean absolute error, weighted interval scores, 95% prediction interval coverage, skill scores and Winkler scores. Overall, then-sub-epidemic modelling framework outcompeted other models across most locations and forecasting horizons, with the unweighted ensemble model performing best most frequently. Then-sub-epidemic and spatial-wave frameworks considerably improved in average forecasting performance relative to the ARIMA model (greater than 10%) for all performance metrics. Findings further support sub-epidemic frameworks for short-term forecasting epidemics of emerging and re-emerging infectious diseases. 

Mathematical models based on systems of ordinary differential equations (ODEs) are frequently applied in various scientific fields to assess hypotheses, estimate key model parameters, and generate predictions about the system's state. To support their application, we present a comprehensive, easy‐to‐use, and flexible MATLAB toolbox,QuantDiffForecast, and associated tutorial to estimate parameters and generate short‐term forecasts with quantified uncertainty from dynamical models based on systems of ODEs. We provide software (https://github.com/gchowell/paramEstimation_forecasting_ODEmodels/) and detailed guidance on estimating parameters and forecasting time‐series trajectories that are characterized using ODEs with quantified uncertainty through a parametric bootstrapping approach. It includes functions that allow the user to infer model parameters and assess forecasting performance for different ODE models specified by the user, using different estimation methods and error structures in the data. The tutorial is intended for a diverse audience, including students training in dynamic systems, and will be broadly applicable to estimate parameters and generate forecasts from models based on ODEs. The functions included in the toolbox are illustrated using epidemic models with varying levels of complexity applied to data from the 1918 influenza pandemic in San Francisco. A tutorial video that demonstrates the functionality of the toolbox is included.