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At least 19 records
All sourcesNASA NTRSDOE OSTI
DOE OSTI2022

Addressing delayed case reporting in infectious disease forecast modeling

Infectious disease forecasting is of great interest to the public health community and policymakers, since forecasts can provide insight into disease dynamics in the near future and inform interventions. Due to delays in case reporting, however, forecasting models may often underestimate the current and future disease burden. In this paper, we propose a general framework for addressing reporting delay in disease forecasting efforts with the goal of improving forecasts. We propose strategies for leveraging either historical data on case reporting or external internet-based data to estimate the amount of reporting error. We then describe several approaches for adapting general forecasting pipelines to account for under- or over-reporting of cases. We apply these methods to address reporting delay in data on dengue fever cases in Puerto Rico from 1990 to 2009 and to reports of influenza-like illness (ILI) in the United States between 2010 and 2019. Through a simulation study, we compare method performance and evaluate robustness to assumption violations. Our results show that forecasting accuracy and prediction coverage almost always increase when correction methods are implemented to address reporting delay. Some of these methods required knowledge about the reporting error or high quality external data, which may not always be available. Provided alternatives include excluding recently-reported data and performing sensitivity analysis. This work provides intuition and guidance for handling delay in disease case reporting and may serve as a useful resource to inform practical infectious disease forecasting efforts.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

Warning Signs of Potential Black Swan Outbreaks in Infectious Disease

Black swan events in infectious disease describe rare but devastatingly large outbreaks. While experts are skeptical that such events are predictable, it might be possible to identify the warning signs of a black swan event. Specifically, following the initiation of an outbreak, key differentiating features could serve as alerts. Such features could be derived from meta-analyses of large outbreaks for multiple infectious diseases. We hypothesized there may be common features among the pathogen, environment, and host epidemiological triad that characterize an infectious disease black swan event. Using Los Alamos National Laboratory’s tool, Analytics for Investigation of Disease Outbreaks, we investigated historical disease outbreak information and anomalous events for several infectious diseases. By studying 32 different infectious diseases and global outbreaks, we observed that in the past 20–30 years, there have been potential black swan events in the majority of infectious diseases analyzed. Importantly, these potential black swan events cannot be attributed to the first introduction of the disease to a susceptible host population. This paper describes our observations and perspectives and illustrates the value of broad analysis of data across the infectious disease realm, providing insights that may not be possible when we focus on singular infectious agents or diseases. Data analytics could be developed to warn health authorities at the beginning of an outbreak of an impending black swan event. Such tools could complement traditional epidemiological modeling to help forecast future large outbreaks and facilitate timely warning and effective, targeted resource allocation for mitigation efforts.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

Regional Relative Risk, a Physics-Based Metric for Characterizing Airborne Infectious Disease Transmission

Airborne infectious disease transmission events occur over a wide range of spatial scales and can be an important means of disease transmission. Physics- and biology-based models can assist in predicting airborne transmission events, overall disease incidence, and disease control strategy efficacy. We describe a new theory that extends current approaches for the case in which an individual is infected by a single airborne particle, including the scenario in which numerous infectious particles are present in the air but only one causes infection. A single infectious particle can contain more than one pathogenic microorganism and be physically larger than the pathogen itself. This approach allows robust relative risk estimates even when there is wide variation in (i) individual exposures and (ii) the individual response to that exposure (the pathogen dose-response function can take any mathematical form and vary by individual). Based on this theory, we propose the regional relative risk—a new metric, distinct from the traditional relative risk metric, that compares the risk between two regions. In theory, these regions can range from individual rooms to large geographic areas. In this paper, we apply the regional relative risk metric to outdoor disease transmission events over spatial scales ranging from 50 m to 20 km, demonstrating that in many common cases minimal input information is required to use the metric. Also, we demonstrate that the model predictions are consistent with data from prior outbreaks. Future efforts could apply and validate this theory for other spatial scales, such as transmission within indoor environments. This work provides context for (i) the initial stages of an airborne disease outbreak and (ii) larger-scale disease spread, including unexpected low-probability disease “sparks” that potentially affect remote populations, a key practical issue in controlling airborne disease outbreaks.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2022

A Comparison of Infectious Disease Forecasting Methods across Locations, Diseases, and Time

Accurate infectious disease forecasting can inform efforts to prevent outbreaks and mitigate adverse impacts. This study compares the performance of statistical, machine learning (ML), and deep learning (DL) approaches in forecasting infectious disease incidences across different countries and time intervals. We forecasted three diverse diseases: campylobacteriosis, typhoid, and Q-fever, using a wide variety of features (n = 46) from public datasets, e.g., landscape, climate, and socioeconomic factors. We compared autoregressive statistical models to two tree-based ML models (extreme gradient boosted trees [XGB] and random forest [RF]) and two DL models (multi-layer perceptron and encoder–decoder model). The disease models were trained on data from seven different countries at the region-level between 2009–2017. Forecasting performance of all models was assessed using mean absolute error, root mean square error, and Poisson deviance across Australia, Israel, and the United States for the months of January through August of 2018. The overall model results were compared across diseases as well as various data splits, including country, regions with highest and lowest cases, and the forecasted months out (i.e., nowcasting, short-term, and long-term forecasting). Overall, the XGB models performed the best for all diseases and, in general, tree-based ML models performed the best when looking at data splits. There were a few instances where the statistical or DL models had minutely smaller error metrics for specific subsets of typhoid, which is a disease with very low case counts. Feature importance per disease was measured by using four tree-based ML models (i.e., XGB and RF with and without region name as a feature). The most important feature groups included previous case counts, region name, population counts and density, mortality causes of neonatal to under 5 years of age, sanitation factors, and elevation. This study demonstrates the power of ML approaches to incorporate a wide range of factors to forecast various diseases, regardless of location, more accurately than traditional statistical approaches.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2025

Including frameworks of public health ethics in computational modelling of infectious disease interventions

Decisions on public health interventions to control infectious diseases are often informed by computational models. Interpreting the predicted outcomes of a public health decision requires not only high-quality modelling but also an ethical framework for assessing the benefits and harms associated with different options. The design and specification of ethical frameworks matured independently of computational modelling, so many values recognized as important for ethical decision-making are missing from computational models. We demonstrate a proof-of-concept approach to incorporate multiple public health values into the evaluation of a simple computational model for vaccination against a pathogen such as SARS-CoV-2. By examining a bounded space of alternative prioritizations of three values relevant to public health ethics (aggregate clinical burden, equity in clinical burden, equity in adverse effects from vaccination), we identify value trade-offs, where the outcomes of optimal strategies differ depending on the ethical framework. This work demonstrates an approach to incorporating diverse values into decision criteria used to evaluate outcomes of models of infectious disease interventions.

"Mathematical Biology"↗
DOE OSTI2025

Ethical considerations in infectious disease modelling for public health policy: the case of school closures

Mathematical models of infectious diseases are frequently used as a tool to support public health policy and decisions around the implementation of interventions such as school closures. However, most publications on policy-relevant modelling lack an ethical framework and do not explicitly consider the ethical implications of the work. This creates a risk that the unintended consequences of interventions are overlooked or that models are used to justify decisions that are inconsistent with public health ethics. In this article, we focus on the case study of school closures as a commonly modelled intervention against pandemic influenza, COVID-19 and other infectious disease threats. We briefly review some of the key concepts in public health ethics and describe approaches to modelling the effects of school closures. We then identify a series of ethical considerations involved in modelling school closures. These include accounting for population heterogeneity and inequalities; including a diversity of viewpoints and expertise in model design; considering the distribution of benefits and harms; and model transparency and contextualization. Furthermore, we conclude with some recommendations to ensure that policy-relevant modelling is consistent with some key ethics values.

97 MATHEMATICS AND COMPUTING↗
DOE OSTI2025

Synthetic method of analogues for emerging infectious disease forecasting

The Method of Analogues (MOA) has gained popularity in the past decade for infectious disease forecasting due to its non-parametric nature. In MOA, the local behavior observed in a time series is matched to the local behaviors of several historical time series. The known values that directly follow the historical time series that best match the observed time series are used to calculate a forecast. This non-parametric approach leverages historical trends to produce forecasts without extensive parameterization, making it highly adaptable. However, MOA is limited in scenarios where historical data is sparse. This limitation was particularly evident during the early stages of the COVID-19 pandemic, where the emerging global epidemic had little-to-no historical data. In this work, we propose a new method inspired by MOA, called the Synthetic Method of Analogues (sMOA). sMOA replaces historical disease data with a library of synthetic data that describe a broad range of possible disease trends. This model circumvents the need to estimate explicit parameter values by instead matching segments of ongoing time series data to a comprehensive library of synthetically generated segments of time series data. We demonstrate that sMOA has competitive performance with state-of-the-art infectious disease forecasting models, out-performing 78% of models from the COVID-19 Forecasting Hub in terms of averaged Mean Absolute Error and 76% of models from the COVID-19 Forecasting Hub in terms of averaged Weighted Interval Score. Additionally, we introduce a novel uncertainty quantification methodology designed for the onset of emerging epidemics. Developing versatile approaches that do not rely on historical data and can maintain high accuracy in the face of novel pandemics is critical for enhancing public health decision-making and strengthening preparedness for future outbreaks.

97 MATHEMATICS AND COMPUTING↗
DOE OSTI2021

Trade-offs between individual and ensemble forecasts of an emerging infectious disease

Probabilistic forecasts play an indispensable role in answering questions about the spread of newly emerged pathogens. However, uncertainties about the epidemiology of emerging pathogens can make it difficult to choose among alternative model structures and assumptions. To assess the potential for uncertainties about emerging pathogens to affect forecasts of their spread, we evaluated the performance 16 forecasting models in the context of the 2015-2016 Zika epidemic in Colombia. Each model featured a different combination of assumptions about human mobility, spatiotemporal variation in transmission potential, and the number of virus introductions. We found that which model assumptions had the most ensemble weight changed through time. We additionally identified a trade-off whereby some individual models outperformed ensemble models early in the epidemic, but on average the ensembles outperformed all individual models. Our results suggest that multiple models spanning uncertainty across alternative assumptions are necessary to obtain robust forecasts for emerging infectious diseases.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2026

Semi-Analytical Hierarchical Bayesian Inference of Nonlinear Model Structure in Stochastic Dynamics: Applied to Compartmental Models of Infectious Diseases

A Bayesian computational framework for parsimonious inference in stochastic nonlinear dynamical systems is presented. This framework enables the concurrent estimation of system states, time-varying parameters, time-invariant parameters, and the optimal sparsity structure of the model parameters. Because differential equation-based models are often simplified mechanistic or phenomenological representations, robust inference from noisy measurement data requires explicit treatment of model error and uncertainty. Model error and time-varying parameters can be represented as random processes, enabling inference while making minimal assumptions about the underlying sources of discrepancy and variability. Adopting stochastic differential equation representations affords the model significant flexibility, but can also render it susceptible to overfitting during statistical inversion, where the inferred model may track noise rather than the underlying signal. To alleviate the effects of overfitting and to enable the discovery of the optimal sparse representation of the time-invariant parameters, a Bayesian sparse learning algorithm is embedded within the framework. This sparse learning framework adopts an approximate hierarchical Bayesian setting defined by a series of semi-analytical expressions. The model structure inference framework is validated using a stochastic compartmental model for tracking and forecasting active cases of an infectious disease. Compartmental models describe population-level infectious disease dynamics through interactions among population fractions grouped by disease state. Mathematically, such models consist of a system of coupled ordinary differential equations. This example adopts an expressive compartmental model that includes multiple possible interactions between disease states, motivated by early uncertainty surrounding COVID-19 reinfection dynamics and their implications for long-term epidemic forecasting. The sparse learning exercise permits the inference of a priori unknown epidemiological dynamics from simulated public health data, discovering the nested compartmental model that optimizes the trade-off between average data-fit and model complexity. It is shown that inducing sparsity among the model parameters eliminates redundant interactions between compartments, equivalently revealing the optimal coupling structure between differential equations.

97 MATHEMATICS AND COMPUTING↗
DOE OSTI2021

Towards prevention and prediction of infectious diseases with virus sterilization using ultraviolet light and low-temperature plasma and bio-sensing devices for health and hygiene care

Inspired by the ideas of many authors, we provide insight on state-of-the-art potential technologies for the prevention and prediction of infectious diseases before they spread. This review also surveys virus sterilization with ultraviolet light and low temperature plasma technologies. Researchers in the various fields of medicine, materials, electronics, and plasma sciences have addressed increasingly challenging demands and the discussion encompasses the major challenges in societies that are faced with the threat of infectious diseases. In addition, technologies that use nanomaterials are evaluated for infection prevention and hygiene purposes. Advances in biomedical diagnostics for health care in terms of complementary metal-oxide-semiconductor transistors-based devices and telemetry for health monitoring are also reviewed.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2025

Meeting Global Health Needs via Infectious Disease Forecasting: Development of a Reliable Data-Driven Framework

Infectious diseases (IDs) have a significant detrimental impact on global health. Timely and accurate ID forecasting can result in more informed implementation of control measures and prevention policies. To meet the operational decision-making needs of real-world circumstances, we aimed to build a standardized, reliable, and trustworthy ID forecasting pipeline and visualization dashboard that is generalizable across a wide range of modeling techniques, IDs, and global locations. We forecasted 6 diverse, zoonotic diseases (brucellosis, campylobacteriosis, Middle East respiratory syndrome, Q fever, tick-borne encephalitis, and tularemia) across 4 continents and 8 countries. We included a wide range of statistical, machine learning, and deep learning models (n=9) and trained them on a multitude of features (average n=2326) within the One Health landscape, including demography, landscape, climate, and socioeconomic factors. The pipeline and dashboard were created in consideration of crucial operational metrics—prediction accuracy, computational efficiency, spatiotemporal generalizability, uncertainty quantification, and interpretability—which are essential to strategic data-driven decisions. While no single best model was suitable for all disease, region, and country combinations, our ensemble technique selects the best-performing model for each given scenario to achieve the closest prediction. For new or emerging diseases in a region, the ensemble model can predict how the disease may behave in the new region using a pretrained model from a similar region with a history of that disease. The data visualization dashboard provides a clean interface of important analytical metrics, such as ID temporal patterns, forecasts, prediction uncertainties, and model feature importance across all geographic locations and disease combinations. As the need for real-time, operational ID forecasting capabilities increases, this standardized and automated platform for data collection, analysis, and reporting is a major step forward in enabling evidence-based public health decisions and policies for the prevention and mitigation of future ID outbreaks.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2024

Transboundary determinants of avian zoonotic infectious diseases: challenges for strengthening research capacity and connecting surveillance networks

As the climate changes, global systems have become increasingly unstable and unpredictable. This is particularly true for many disease systems, including subtypes of highly pathogenic avian influenzas (HPAIs) that are circulating the world. Ecological patterns once thought stable are changing, bringing new populations and organisms into contact with one another. Wild birds continue to be hosts and reservoirs for numerous zoonotic pathogens, and strains of HPAI and other pathogens have been introduced into new regions via migrating birds and transboundary trade of wild birds. With these expanding environmental changes, it is even more crucial that regions or counties that previously did not have surveillance programs develop the appropriate skills to sample wild birds and add to the understanding of pathogens in migratory and breeding birds through research. For example, little is known about wild bird infectious diseases and migration along the Mediterranean and Black Sea Flyway (MBSF), which connects Europe, Asia, and Africa. Focusing on avian influenza and the microbiome in migratory wild birds along the MBSF, this project seeks to understand the determinants of transboundary disease propagation and coinfection in regions that are connected by this flyway. Through the creation of a threat reduction network for avian diseases (Avian Zoonotic Disease Network, AZDN) in three countries along the MBSF (Georgia, Ukraine, and Jordan), this project is strengthening capacities for disease diagnostics; microbiomes; ecoimmunology; field biosafety; proper wildlife capture and handling; experimental design; statistical analysis; and vector sampling and biology. Here, we cover what is required to build a wild bird infectious disease research and surveillance program, which includes learning skills in proper bird capture and handling; biosafety and biosecurity; permits; next generation sequencing; leading-edge bioinformatics and statistical analyses; and vector and environmental sampling. Creating connected networks for avian influenzas and other pathogen surveillance will increase coordination and strengthen biosurveillance globally in wild birds.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2021

Lab Home Testing of Residential Isolation Space Control to Minimize Infectious Disease Transmission in Existing Single-Family Homes

Existing evidence strongly suggests that viral infectious diseases can be transmitted via an airborne route across distances in indoor environments. Accordingly, the risk of airborne transmission within homes should be managed. The public health emergency associated with SARS-CoV-2 makes controlling airborne transmission of respired viruses in indoor environments critical, especially in poorly ventilated indoor environments. The effectiveness of engineering interventions requiring minor efforts that create a negative-pressure isolation zone (IZ) for a contagious person has yet to be tested for existing residential homes. To mitigate the risk of airborne virus transmission and maximize health protection for the population in existing single-family homes, the relative effectiveness of several control strategies are investigated in this report. While very high-efficiency MERV filtration, high ventilation rates, and other controls can help be effective, most occupants are not likely to have the time or means for advanced measures found in hospitals. This project focused on testing relatively simple efforts that utilize existing or easy to acquire materials and simple processes.

32 ENERGY CONSERVATION, CONSUMPTION, AND UTILIZATI↗
DOE OSTI2021

Lab Home Testing of Residential Isolation Space Control to Minimize Infectious Disease Transmission in Existing Single-Family Homes

Existing evidence strongly suggests that viral infectious diseases can be transmitted via an airborne route across distances in indoor environments. Accordingly, the risk of airborne transmission within homes should be managed. The public health emergency associated with SARS-CoV-2 makes controlling airborne transmission of respired viruses in indoor environments critical, especially in poorly ventilated indoor environments. The effectiveness of engineering interventions requiring minor efforts that create a negative-pressure isolation zone (IZ) for a contagious person has yet to be tested for existing residential homes. To mitigate the risk of airborne virus transmission and maximize health protection for the population in existing single-family homes, the relative effectiveness of several control strategies are investigated in this report. While very high-efficiency MERV filtration, high ventilation rates, and other controls can help be effective, most occupants are not likely to have the time or means for advanced measures found in hospitals. This project focused on testing relatively simple efforts that utilize existing or easy to acquire materials and simple processes.

30 DIRECT ENERGY CONVERSION↗
DOE OSTI2022

Machine Learning in Infectious Disease for Risk Factor Identification and Hypothesis Generation: Proof of Concept Using Invasive Candidiasis

Machine learning (ML) models can handle large data sets without assuming underlying relationships and can be useful for evaluating disease characteristics, yet they are more commonly used for predicting individual disease risk than for identifying factors at the population level. We offer a proof of concept applying random forest (RF) algorithms to Candida-positive hospital encounters in an electronic health record database of patients in the United States. Candida-positive encounters were extracted from the Cerner HealthFacts database; invasive infections were laboratory-positive sterile site Candida infections. Features included demographics, admission source, care setting, physician specialty, diagnostic and procedure codes, and medications received before the first positive Candida culture. We used RF to assess risk factors for 3 outcomes: any invasive candidiasis (IC) vs non-IC, within-species IC vs non-IC (eg, invasive C. glabrata vs noninvasive C. glabrata), and between-species IC (eg, invasive C. glabrata vs all other IC). Fourteen of 169 (8%) variables were consistently identified as important features in the ML models. When evaluating within-species IC, for example, invasive C. glabrata vs non-invasive C. glabrata, we identified known features like central venous catheters, intensive care unit stay, and gastrointestinal operations. In contrast, important variables for invasive C. glabrata vs all other IC included renal disease and medications like diabetes therapeutics, cholesterol medications, and antiarrhythmics. Known and novel risk factors for IC were identified using ML, demonstrating the hypothesis-generating utility of this approach for infectious disease conditions about which less is known, specifically at the species level or for rarer diseases.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2022

Cooperative Research and Infectious Disease Surveillance: A 2021 Epilogue

As the world looks forward to turning a corner in the face of the COVID-19 pandemic, it becomes increasingly evident that international research cooperation and dialogue is necessary to end this global catastrophe. Last year, we initiated a research topic: “Infectious Disease Surveillance: Cooperative Research in Response to Recent Outbreaks, Including COVID-19,” which aimed at featuring manuscripts focused on the essential link between surveillance and cooperative research for emerging and endemic diseases, and highlighting scientific partnerships in countries under-represented in the scientific literature. Here we recognize the body of work published from our manuscript call that resulted in over 50 published papers. This current analysis describes articles and authors from a variety of funded and unfunded international sources. The work exemplifies successful research and publications which are frequently cooperative, and may serve as a basis to model further global scientific engagements.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2022

Alternative SIAR models for infectious diseases and applications in the study of non-compliance

In this paper, we use modified versions of the SIAR model for epidemics to propose two ways of understanding and quantifying the effect of non-compliance to non-pharmaceutical intervention measures on the spread of an infectious disease. The SIAR model distinguishes between symptomatic infected (I) and asymptomatic infected (A) populations. One modification, which is simpler, assumes a known proportion of the population does not comply with government mandates such as quarantining and social-distancing. In a more sophisticated approach, the modified model treats non-compliant behavior as a social contagion. We theoretically explore different scenarios such as the occurrence of multiple waves of infections. Local and asymptotic analyses for both models are also provided.

Mathematics↗