Improving Risk Prediction of Methicillin-Resistant Staphylococcus aureus Using Machine Learning Methods With Network Features: Retrospective Development Study.

BACKGROUND: Health care-associated infections due to multidrug-resistant organisms (MDROs), such as methicillin-resistant Staphylococcus aureus (MRSA) and Clostridioides difficile (CDI), place a significant burden on our health care infrastructure. OBJECTIVE: Screening for MDROs is an important mechanism for preventing spread but is resource intensive. The objective of this study was to develop automated tools that can predict colonization or infection risk using electronic health record (EHR) data, provide useful information to aid infection control, and guide empiric antibiotic coverage. METHODS: We retrospectively developed a machine learning model to detect MRSA colonization and infection in undifferentiated patients at the time of sample collection from hospitalized patients at the University of Virginia Hospital. We used clinical and nonclinical features derived from on-admission and throughout-stay information from the patient's EHR data to build the model. In addition, we used a class of features derived from contact networks in EHR data; these network features can capture patients' contacts with providers and other patients, improving model interpretability and accuracy for predicting the outcome of surveillance tests for MRSA. Finally, we explored heterogeneous models for different patient subpopulations, for example, those admitted to an intensive care unit or emergency department or those with specific testing histories, which perform better. RESULTS: We found that the penalized logistic regression performs better than other methods, and this model's performance measured in terms of its receiver operating characteristics-area under the curve score improves by nearly 11% when we use polynomial (second-degree) transformation of the features. Some significant features in predicting MDRO risk include antibiotic use, surgery, use of devices, dialysis, patient's comorbidity conditions, and network features. Among these, network features add the most value and improve the model's performance by at least 15%. The penalized logistic regression model with the same transformation of features also performs better than other models for specific patient subpopulations. CONCLUSIONS: Our study shows that MRSA risk prediction can be conducted quite effectively by machine learning methods using clinical and nonclinical features derived from EHR data. Network features are the most predictive and provide significant improvement over prior methods. Furthermore, heterogeneous prediction models for different patient subpopulations enhance the model's performance.

Novel multi-cluster workflow system to support real-time HPC-enabled epidemic science: Investigating the impact of vaccine acceptance on COVID-19 spread.

We present MacKenzie, a HPC-driven multi-cluster workflow system that was used repeatedly to configure and execute fine-grained US national-scale epidemic simulation models during the COVID-19 pandemic. Mackenzie supported federal and Virginia policymakers, in real-time, for a large number of "what-if" scenarios during the COVID-19 pandemic, and continues to be used to answer related questions as COVID-19 transitions to the endemic stage of the disease. MacKenzie is a novel HPC meta-scheduler that can execute US-scale simulation models and associated workflows that typically present significant big data challenges. The meta-scheduler optimizes the total execution time of simulations in the workflow, and helps improve overall human productivity. As an exemplar of the kind of studies that can be conducted using Mackenzie, we present a modeling study to understand the impact of vaccine-acceptance in controlling the spread of COVID-19 in the US. We use a 288 million node synthetic social contact network (digital twin) spanning all 50 US states plus Washington DC, comprised of 3300 counties, with 12 billion daily interactions. The highly-resolved agent-based model used for the epidemic simulations uses realistic information about disease progression, vaccine uptake, production schedules, acceptance trends, prevalence, and social distancing guidelines. Computational experiments show that, for the simulation workload discussed above, MacKenzie is able to scale up well to 10K CPU cores. Our modeling results show that, when compared to faster and accelerating vaccinations, slower vaccination rates due to vaccine hesitancy cause averted infections to drop from 6.7M to 4.5M, and averted total deaths to drop from 39.4K to 28.2K across the US. This occurs despite the fact that the final vaccine coverage is the same in both scenarios. We also find that if vaccine acceptance could be increased by 10% in all states, averted infections could be increased from 4.5M to 4.7M (a 4.4% improvement) and total averted deaths could be increased from 28.2K to 29.9K (a 6% improvement) nationwide.

Data-driven mechanistic framework with stratified immunity and effective transmissibility for COVID-19 scenario projections.

Scenario-based modeling frameworks have been widely used to support policy-making at state and federal levels in the United States during the COVID-19 response. While custom-built models can be used to support one-off studies, sustained updates to projections under changing pandemic conditions requires a robust, integrated, and adaptive framework. In this paper, we describe one such framework, UVA-adaptive, that was built to support the CDC-aligned Scenario Modeling Hub (SMH) across multiple rounds, as well as weekly/biweekly projections to Virginia Department of Health (VDH) and US Department of Defense during the COVID-19 response. Building upon an existing metapopulation framework, PatchSim, UVA-adaptive uses a calibration mechanism relying on adjustable effective transmissibility as a basis for scenario definition while also incorporating real-time datasets on case incidence, seroprevalence, variant characteristics, and vaccine uptake. Through the pandemic, our framework evolved by incorporating available data sources and was extended to capture complexities of multiple strains and heterogeneous immunity of the population. Here we present the version of the model that was used for the recent projections for SMH and VDH, describe the calibration and projection framework, and demonstrate that the calibrated transmissibility correlates with the evolution of the pathogen as well as associated societal dynamics.

Modeling relaxed policies for discontinuation of methicillin-resistant Staphylococcus aureus contact precautions.

OBJECTIVE: To evaluate the economic costs of reducing the University of Virginia Hospital's present "3-negative" policy, which continues methicillin-resistant Staphylococcus aureus (MRSA) contact precautions until patients receive 3 consecutive negative test results, to either 2 or 1 negative. DESIGN: Cost-effective analysis. SETTINGS: The University of Virginia Hospital. PATIENTS: The study included data from 41,216 patients from 2015 to 2019. METHODS: We developed a model for MRSA transmission in the University of Virginia Hospital, accounting for both environmental contamination and interactions between patients and providers, which were derived from electronic health record (EHR) data. The model was fit to MRSA incidence over the study period under the current 3-negative clearance policy. A counterfactual simulation was used to estimate outcomes and costs for 2- and 1-negative policies compared with the current 3-negative policy. RESULTS: Our findings suggest that 2-negative and 1-negative policies would have led to 6 (95% CI, -30 to 44; P < .001) and 17 (95% CI, -23 to 59; -10.1% to 25.8%; P < .001) more MRSA cases, respectively, at the hospital over the study period. Overall, the 1-negative policy has statistically significantly lower costs ($628,452; 95% CI, $513,592-$752,148) annually (P < .001) in US dollars, inflation-adjusted for 2023) than the 2-negative policy ($687,946; 95% CI, $562,522-$812,662) and 3-negative ($702,823; 95% CI, $577,277-$846,605). CONCLUSIONS: A single negative MRSA nares PCR test may provide sufficient evidence to discontinue MRSA contact precautions, and it may be the most cost-effective option.

Coupled models of genomic surveillance and evolving pandemics with applications for timely public health interventions.

Disease surveillance systems provide early warnings of disease outbreaks before they become public health emergencies. However, pandemics containment would be challenging due to the complex immunity landscape created by multiple variants. Genomic surveillance is critical for detecting novel variants with diverse characteristics and importation/emergence times. Yet, a systematic study incorporating genomic monitoring, situation assessment, and intervention strategies is lacking in the literature. We formulate an integrated computational modeling framework to study a realistic course of action based on sequencing, analysis, and response. We study the effects of the second variant's importation time, its infectiousness advantage and, its cross-infection on the novel variant's detection time, and the resulting intervention scenarios to contain epidemics driven by two-variants dynamics. Our results illustrate the limitation in the intervention's effectiveness due to the variants' competing dynamics and provide the following insights: i) There is a set of importation times that yields the worst detection time for the second variant, which depends on the first variant's basic reproductive number; ii) When the second variant is imported relatively early with respect to the first variant, the cross-infection level does not impact the detection time of the second variant. We found that depending on the target metric, the best outcomes are attained under different interventions' regimes. Our results emphasize the importance of sustained enforcement of Non-Pharmaceutical Interventions on preventing epidemic resurgence due to importation/emergence of novel variants. We also discuss how our methods can be used to study when a novel variant emerges within a population.

Using spectral characterization to identify healthcare-associated infection (HAI) patients for clinical contact precaution.

Healthcare-associated infections (HAIs) are a major problem in hospital infection control. Although HAIs can be suppressed using contact precautions, such precautions are expensive, and we can only apply them to a small fraction of patients (i.e., a limited budget). In this work, we focus on two clinical problems arising from the limited budget: (a) choosing the best patients to be placed under precaution given a limited budget to minimize the spread (the isolation problem), and (b) choosing the best patients to release when limited budget requires some of the patients to be cleared from precaution (the clearance problem). A critical challenge in addressing them is that HAIs have multiple transmission pathways such that locations can also accumulate 'load' and spread the disease. One of the most common practices when placing patients under contact precautions is the regular clearance of pathogen loads. However, standard propagation models like independent cascade (IC)/susceptible-infectious-susceptible (SIS) cannot capture such mechanisms directly. Hence to account for this challenge, using non-linear system theory, we develop a novel spectral characterization of a recently proposed pathogen load based model, 2-MODE-SIS model, on people/location networks to capture spread dynamics of HAIs. We formulate the two clinical problems using this spectral characterization and develop effective and efficient algorithms for them. Our experiments show that our methods outperform several natural structural and clinical approaches on real-world hospital testbeds and pick meaningful solutions.

Are all underimmunized measles clusters equally critical?

This research develops a novel system science approach to examine the potential risk of outbreaks caused by geographical clustering of underimmunized individuals for an infectious disease like measles. We use an activity-based population network model and school immunization records to identify underimmunized clusters of zip codes in the Commonwealth of Virginia. Although Virginia has high vaccine coverage for measles at the state level, finer-scale investigation at the zip code level finds three statistically significant underimmunized clusters. This research examines why some underimmunized geographical clusters are more critical in causing outbreaks and how their criticality changes with a possible drop in overall vaccination coverage. Results show that different clusters can cause vastly different outbreaks in a region, depending on their size, location, immunization rate and network characteristics. Among the three underimmunized clusters, we find one to be critical and the other two to be benign in terms of an outbreak risk. However, when the vaccine coverage among children drops by just 5% (or 0.8% overall in the population), one of the benign clusters becomes highly critical. This work also examines the demographic and network properties of these clusters to identify factors that are responsible for affecting the criticality of the clusters. Although this work focuses on measles, the methodology is generic and can be applied to study other infectious diseases.

Spatial-Temporal Networks for Antibiogram Pattern Prediction.

An antibiogram is a periodic summary of antibiotic resistance results of organisms from infected patients to selected antimicrobial drugs. Antibiograms help clinicians to understand regional resistance rates and select appropriate antibiotics in prescriptions. In practice, significant combinations of antibiotic resistance may appear in different antibiograms, forming antibiogram patterns. Such patterns may imply the prevalence of some infectious diseases in certain regions. Thus it is of crucial importance to monitor antibiotic resistance trends and track the spread of multi-drug resistant organisms. In this paper, we propose a novel problem of antibiogram pattern prediction that aims to predict which patterns will appear in the future. Despite its importance, tackling this problem encounters a series of challenges and has not yet been explored in the literature. First of all, antibiogram patterns are not i.i.d as they may have strong relations with each other due to genomic similarities of the underlying organisms. Second, antibiogram patterns are often temporally dependent on the ones that are previously detected. Furthermore, the spread of antibiotic resistance can be significantly influenced by nearby or similar regions. To address the above challenges, we propose a novel Spatial-Temporal Antibiogram Pattern Prediction framework, STAPP, that can effectively leverage the pattern correlations and exploit the temporal and spatial information. We conduct extensive experiments on a real-world dataset with antibiogram reports of patients from 1999 to 2012 for 203 cities in the United States. The experimental results show the superiority of STAPP against several competitive baselines.

Are all underimmunized measles clusters equally critical?

Disruptions in routine immunizations due to the COVID-19 pandemic have been a cause of significant concern for health organizations worldwide. This research develops a system science approach to examine the potential risk of geographical clustering of underimmunized individuals for an infectious disease like measles. We use an activity-based population network model and school immunization records to identify underimmunized clusters of zip codes in the Commonwealth of Virginia. Although Virginia has high vaccine coverage at the state level for measles, finer-scale investigation at the zip code level finds three statistically significant underimmunized clusters. To estimate the criticality of these clusters, a stochastic agent-based network epidemic model is used. Results show that different clusters can cause vastly different outbreaks in the region, depending on their size, location, and network characteristics. This research aims to understand why some underimmunized geographical clusters do not cause a large outbreak while others do. A detailed network analysis shows that it is not the average degree of the cluster or the percentage of underimmunized individuals in the cluster but the average eigenvector centrality of the cluster that is important in determining its potential risk.

Airborne disease transmission during indoor gatherings over multiple time scales: Modeling framework and policy implications.

Indoor superspreading events are significant drivers of transmission of respiratory diseases. In this work, we study the dynamics of airborne transmission in consecutive meetings of individuals in enclosed spaces. In contrast to the usual pairwise-interaction models of infection where effective contacts transmit the disease, we focus on group interactions where individuals with distinct health states meet simultaneously. Specifically, the disease is transmitted by infected individuals exhaling droplets (contributing to the viral load in the closed space) and susceptible ones inhaling the contaminated air. We propose a modeling framework that couples the fast dynamics of the viral load attained over meetings in enclosed spaces and the slow dynamics of disease progression at the population level. Our modeling framework incorporates the multiple time scales involved in different setups in which indoor events may happen, from single-time events to events hosting multiple meetings per day, over many days. We present theoretical and numerical results of trade-offs between the room characteristics (ventilation system efficiency and air mass) and the group's behavioral and composition characteristics (group size, mask compliance, testing, meeting time, and break times), that inform indoor policies to achieve disease control in closed environments through different pathways. Our results emphasize the impact of break times, mask-wearing, and testing on facilitating the conditions to achieve disease control. We study scenarios of different break times, mask compliance, and testing. We also derive policy guidelines to contain the infection rate under a certain threshold.

High resolution synthetic residential energy use profiles for the United States.

Efficient energy consumption is crucial for achieving sustainable energy goals in the era of climate change and grid modernization. Thus, it is vital to understand how energy is consumed at finer resolutions such as household in order to plan demand-response events or analyze impacts of weather, electricity prices, electric vehicles, solar, and occupancy schedules on energy consumption. However, availability and access to detailed energy-use data, which would enable detailed studies, has been rare. In this paper, we release a unique, large-scale, digital-twin of residential energy-use dataset for the residential sector across the contiguous United States covering millions of households. The data comprise of hourly energy use profiles for synthetic households, disaggregated into Thermostatically Controlled Loads (TCL) and appliance use. The underlying framework is constructed using a bottom-up approach. Diverse open-source surveys and first principles models are used for end-use modeling. Extensive validation of the synthetic dataset has been conducted through comparisons with reported energy-use data. We present a detailed, open, high resolution, residential energy-use dataset for the United States.

Data-driven scalable pipeline using national agent-based models for real-time pandemic response and decision support.

This paper describes an integrated, data-driven operational pipeline based on national agent-based models to support federal and state-level pandemic planning and response. The pipeline consists of (i) an automatic semantic-aware scheduling method that coordinates jobs across two separate high performance computing systems; (ii) a data pipeline to collect, integrate and organize national and county-level disaggregated data for initialization and post-simulation analysis; (iii) a digital twin of national social contact networks made up of 288 Million individuals and 12.6 Billion time-varying interactions covering the US states and DC; (iv) an extension of a parallel agent-based simulation model to study epidemic dynamics and associated interventions. This pipeline can run 400 replicates of national runs in less than 33 h, and reduces the need for human intervention, resulting in faster turnaround times and higher reliability and accuracy of the results. Scientifically, the work has led to significant advances in real-time epidemic sciences.

A Framework for the Comparison of Agent-based Models.

We develop a methodology for comparing agent-based models that are developed for the same domain, but may differ in the data sets (e.g., geographical regions) to which they are applied, and in the structure of the model. Our approach is to learn a response surface in the common parameter space of the models and compare the regions corresponding to qualitatively different behaviors in the models. As an example, we develop an active learning algorithm to learn phase shift boundaries in contagion processes in order to compare two agent-based models of rooftop solar panel adoption developed for different regions. We present results for 2D and 3D subspaces of the parameter space, though the approach scales to higher dimensions as well.

Ensembles of realistic power distribution networks.

The power grid is going through significant changes with the introduction of renewable energy sources and the incorporation of smart grid technologies. These rapid advancements necessitate new models and analyses to keep up with the various emergent phenomena they induce. A major prerequisite of such work is the acquisition of well-constructed and accurate network datasets for the power grid infrastructure. In this paper, we propose a robust, scalable framework to synthesize power distribution networks that resemble their physical counterparts for a given region. We use openly available information about interdependent road and building infrastructures to construct the networks. In contrast to prior work based on network statistics, we incorporate engineering and economic constraints to create the networks. Additionally, we provide a framework to create ensembles of power distribution networks to generate multiple possible instances of the network for a given region. The comprehensive dataset consists of nodes with attributes, such as geocoordinates; type of node (residence, transformer, or substation); and edges with attributes, such as geometry, type of line (feeder lines, primary or secondary), and line parameters. For validation, we provide detailed comparisons of the generated networks with actual distribution networks. The generated datasets represent realistic test systems (as compared with standard test cases published by Institute of Electrical and Electronics Engineers (IEEE)) that can be used by network scientists to analyze complex events in power grids and to perform detailed sensitivity and statistical analyses over ensembles of networks.

COVID's collateral damage: likelihood of measles resurgence in the United States.

BACKGROUND: Lockdowns imposed throughout the US to control the COVID-19 pandemic led to a decline in all routine immunizations rates, including the MMR (measles, mumps, rubella) vaccine. It is feared that post-lockdown, these reduced MMR rates will lead to a resurgence of measles. METHODS: To measure the potential impact of reduced MMR vaccination rates on measles outbreak, this research examines several counterfactual scenarios in pre-COVID-19 and post-COVID-19 era. An agent-based modeling framework is used to simulate the spread of measles on a synthetic yet realistic social network of Virginia. The change in vulnerability of various communities to measles due to reduced MMR rate is analyzed. RESULTS: Results show that a decrease in vaccination rate [Formula: see text] has a highly non-linear effect on the number of measles cases and this effect grows exponentially beyond a threshold [Formula: see text]. At low vaccination rates, faster isolation of cases and higher compliance to home-isolation are not enough to control the outbreak. The overall impact on urban and rural counties is proportional to their population size but the younger children, African Americans and American Indians are disproportionately infected and hence are more vulnerable to the reduction in the vaccination rate. CONCLUSIONS: At low vaccination rates, broader interventions are needed to control the outbreak. Identifying the cause of the decline in vaccination rates (e.g., low income) can help design targeted interventions which can dampen the disproportional impact on more vulnerable populations and reduce disparities in health. Per capita burden of the potential measles resurgence is equivalent in the rural and the urban communities and hence proportionally equitable public health resources should be allocated to rural regions.

Understanding the coevolution of mask wearing and epidemics: A network perspective.

Nonpharmaceutical interventions (NPIs) such as mask wearing can be effective in mitigating the spread of infectious diseases. Therefore, understanding the behavioral dynamics of NPIs is critical for characterizing the dynamics of disease spread. Nevertheless, standard infection models tend to focus only on disease states, overlooking the dynamics of "beneficial contagions," e.g., compliance with NPIs. In this work, we investigate the concurrent spread of disease and mask-wearing behavior over multiplex networks. Our proposed framework captures both the competing and complementary relationships between the dueling contagion processes. Further, the model accounts for various behavioral mechanisms that influence mask wearing, such as peer pressure and fear of infection. Our results reveal that under the coupled disease-behavior dynamics, the attack rate of a disease-as a function of transition probability-exhibits a critical transition. Specifically, as the transmission probability exceeds a critical threshold, the attack rate decreases abruptly due to sustained mask-wearing responses. We empirically explore the causes of the critical transition and demonstrate the robustness of the observed phenomena. Our results highlight that without proper enforcement of NPIs, reductions in the disease transmission probability via other interventions may not be sufficient to reduce the final epidemic size.

Projected resurgence of COVID-19 in the United States in July-December 2021 resulting from the increased transmissibility of the Delta variant and faltering vaccination.

In Spring 2021, the highly transmissible SARS-CoV-2 Delta variant began to cause increases in cases, hospitalizations, and deaths in parts of the United States. At the time, with slowed vaccination uptake, this novel variant was expected to increase the risk of pandemic resurgence in the US in summer and fall 2021. As part of the COVID-19 Scenario Modeling Hub, an ensemble of nine mechanistic models produced 6-month scenario projections for July-December 2021 for the United States. These projections estimated substantial resurgences of COVID-19 across the US resulting from the more transmissible Delta variant, projected to occur across most of the US, coinciding with school and business reopening. The scenarios revealed that reaching higher vaccine coverage in July-December 2021 reduced the size and duration of the projected resurgence substantially, with the expected impacts was largely concentrated in a subset of states with lower vaccination coverage. Despite accurate projection of COVID-19 surges occurring and timing, the magnitude was substantially underestimated 2021 by the models compared with the of the reported cases, hospitalizations, and deaths occurring during July-December, highlighting the continued challenges to predict the evolving COVID-19 pandemic. Vaccination uptake remains critical to limiting transmission and disease, particularly in states with lower vaccination coverage. Higher vaccination goals at the onset of the surge of the new variant were estimated to avert over 1.5 million cases and 21,000 deaths, although may have had even greater impacts, considering the underestimated resurgence magnitude from the model.

Deploying Vaccine Distribution Sites for Improved Accessibility and Equity to Support Pandemic Response.

In response to COVID-19, many countries have mandated social distancing and banned large group gatherings in order to slow down the spread of SARS-CoV-2. These social interventions along with vaccines remain the best way forward to reduce the spread of SARS CoV-2. In order to increase vaccine accessibility, states such as Virginia have deployed mobile vaccination centers to distribute vaccines across the state. When choosing where to place these sites, there are two important factors to take into account: accessibility and equity. We formulate a combinatorial problem that captures these factors and then develop efficient algorithms with theoretical guarantees on both of these aspects. Furthermore, we study the inherent hardness of the problem, and demonstrate strong impossibility results. Finally, we run computational experiments on real-world data to show the efficacy of our methods.

Fundamental limitations on efficiently forecasting certain epidemic measures in network models.

The ongoing COVID-19 pandemic underscores the importance of developing reliable forecasts that would allow decision makers to devise appropriate response strategies. Despite much recent research on the topic, epidemic forecasting remains poorly understood. Researchers have attributed the difficulty of forecasting contagion dynamics to a multitude of factors, including complex behavioral responses, uncertainty in data, the stochastic nature of the underlying process, and the high sensitivity of the disease parameters to changes in the environment. We offer a rigorous explanation of the difficulty of short-term forecasting on networked populations using ideas from computational complexity. Specifically, we show that several forecasting problems (e.g., the probability that at least a given number of people will get infected at a given time and the probability that the number of infections will reach a peak at a given time) are computationally intractable. For instance, efficient solvability of such problems would imply that the number of satisfying assignments of an arbitrary Boolean formula in conjunctive normal form can be computed efficiently, violating a widely believed hypothesis in computational complexity. This intractability result holds even under the ideal situation, where all the disease parameters are known and are assumed to be insensitive to changes in the environment. From a computational complexity viewpoint, our results, which show that contagion dynamics become unpredictable for both macroscopic and individual properties, bring out some fundamental difficulties of predicting disease parameters. On the positive side, we develop efficient algorithms or approximation algorithms for restricted versions of forecasting problems.