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At least 73 records · Page 4

PRIME

SAND2021-0565 O PRIME is a modeling framework designed for the real-time characterization and forecasting of partially observed epidemics. The method is designed to help guide medical resource allocation in the early epoch of the outbreak. Characterization is the estimation of infection spread parameters using daily counts of symptomatic patients. The estimation problem is posed as one of Bayesian inference and solved using a Markov Chain Monte Carlo technique. The framework can accommodate multiple epidemic waves and can help identify different disease dynamics at the regional, state, and country levels. Examples are provided using publicly available COVID-19 data. Sandia National Laboratories is a multimission laboratory managed and operated by National Technology & Engineering Solutions of Sandia, LLC, a wholly owned subsidiary of Honeywell International Inc., for the U.S. Department of Energy’s National Nuclear Security Administration under contract DE-NA0003525.

Safta, Cosmin↗

Modeling Influenza Transmission Using Environmental Parameters

Influenza is an acute viral respiratory disease that has significant mortality, morbidity and economic burden worldwide. It infects approximately 5-15% of the world population, and causes 250,000 500,000 deaths each year. The role of environments on influenza is often drawn upon the latitude variability of influenza seasonality pattern. In regions with temperate climate, influenza epidemics exhibit clear seasonal pattern that peak during winter months, but it is not as evident in the tropics. Toward this end, we developed mathematical model and forecasting capabilities for influenza in regions characterized by warm climate Hong Kong (China) and Maricopa County (Arizona, USA). The best model for Hong Kong uses Land Surface Temperature (LST), precipitation and relative humidity as its covariates. Whereas for Maricopa County, we found that weekly influenza cases can be best modelled using mean air temperature as its covariates. Our forecasts can further guides public health organizations in targeting influenza prevention and control measures such as vaccination.

Soebiyanto, Radina P.↗

GraMeR: Gra ph Me ta R einforcement learning for multi-objective influence maximization

Influence maximization (IM) is a combinatorial problem of identifying a subset of seed nodes in a network (graph), which when activated, provide a maximal spread of influence in the network for a given diffusion model and a budget for seed set size. IM has numerous applications such as viral marketing, epidemic control, sensor placement and other network-related tasks. However, its practical uses are limited due to the computational complexity of current algorithms. Recently, deep reinforcement learning has been leveraged to solve IM in order to ease the computational burden. However, there are serious limitations in current approaches, including narrow IM formulation that only consider influence via spread and ignore self-activation, low scalability to large graphs, and lack of generalizability across graph families leading to a large running time for every test network. In this work, we address these limitations through a unique approach that involves: (1) Formulating a generic IM problem as a Markov decision process that handles both intrinsic and influence activations; (2)incorporating generalizability via meta-learning across graph families. There are previous works that combine deep reinforcement learning with graph neural network, but this work solves a more realistic IM problem and incorporates generalizability across graphs via meta reinforcement learning. Extensive experiments are carried out in various standard networks to validate performance of the proposed Graph Meta Reinforcement learning (GraMeR) framework. Finally, the results indicate that GraMeR is multiple orders faster and generic than conventional approaches when applied on small to medium scale graphs.

97 MATHEMATICS AND COMPUTING↗

NW-BRaVE T3 Hydroplane Project Close: Project Close-out for T3 Hydroplane Analysis

Thrust 3 of the Northwest Biopreparedness Research in a Virtual Environment was an expansive project including method development, sample collection and sequence analysis. The sampling occurred over a multi-year period to generate metagenomic datasets that inform cyanophage-picocyanobacterial interactions in the Salish Sea across a moderate timeframe and geographical range. Part of the thrust’s aim was to validate how much experimental structural and multiomics work in a model organism (Prochlorococcus Marinus, str. MED4) from thrusts 1 and 2 would carry over into a broader range of related organisms in the natural world, to address a fundamental question in scientific preparation for epidemics: whether and how much experimental information from known and experimentally tractable species can translate to actionable biological information in unknown species. In other words, thrust 3 aimed to find out whether the model organism experiments matter in terms of how organisms interact. This report updates work described in Johnson and Pollock 2025 (1).

54 ENVIRONMENTAL SCIENCES↗

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↗

Simulating nationwide coupled disease and fear spread in an agent-based model

Human cognitive responses, behavioral responses, and disease dynamics co-evolve over the course of any disease outbreak, and can result in complex feedbacks. We present a dynamic agent-based model that explicitly couples the spread of disease with the spread of fear surrounding the disease, implemented within the EpiCast simulation framework. EpiCast models transmission within a realistic synthetic population, capturing individual-level interactions. In our model, fear propagates through both in-person contact and broadcast media, prompting individuals to adopt protective behaviors that reduce disease spread. In order to better understand these coupled dynamics, we create and compare a range of compartmental models to ensure that introducing additional disease states does not prevent the emergence of multiple waves in these simpler models. Additionally, we compare a range of behavioral scenarios within EpiCast, varying the level and intensity of fear and behavior change. Our results show that the addition of asymptomatic, exposed, and pre-symptomatic disease states can impact both the rate at which an outbreak progresses and its overall trajectory in compartmental models. In EpiCast, the combination of non-local fear spread via broadcasters and strong behavioral responses by fearful individuals generally leads to multiple epidemic waves, an outcome that occurs only within a narrow parameter range when fear spreads purely through local contact. Accounting for the coupled spread of fear and disease is critical for understanding disease dynamics and designing timely, targeted responses to emerging infectious threats.

60 APPLIED LIFE SCIENCES↗

AeDES: a next-generation monitoring and forecasting system for environmental suitability of Aedes-borne disease transmission

Aedes-borne diseases, such as dengue and chikungunya, are responsible for more than 50 million infections worldwide every year, with an overall increase of 30-fold in the last 50 years, mainly due to city population growth, more frequent travels and ecological changes. In the United States of America, the vast majority of Aedes-borne infections are imported from endemic regions by travelers, who can become new sources of mosquito infection upon their return home if the exposed population is susceptible to the disease, and if suitable environmental conditions for the mosquitoes and the virus are present. Since the susceptibility of the human population can be determined via periodic monitoring campaigns, the environmental suitability for the presence of mosquitoes and viruses becomes one of the most important pieces of information for decision makers in the health sector. We present a next-generation monitoring and forecasting system for Aedes-borne diseases’ environmental suitability (AeDES) of transmission in the conterminous United States and transboundary regions, using calibrated ento-epidemiological models, climate models and temperature observations. After analyzing the seasonal predictive skill of AeDES, we briefly consider the recent Zika epidemic, and the compound effects of the current Central American dengue outbreak happening during the SARS-CoV-2 pandemic, to illustrate how a combination of tailored deterministic and probabilistic forecasts can inform key prevention and control strategies .

54 ENVIRONMENTAL SCIENCES↗

Single Amino Acid Mutations Affect Zika Virus Replication In Vitro and Virulence In Vivo

The 2014–2016 Zika virus (ZIKV) epidemic in the Americas resulted in large deposits of next-generation sequencing data from clinical samples. This resource was mined to identify emerging mutations and trends in mutations as the outbreak progressed over time. Information on transmission dynamics, prevalence, and persistence of intra-host mutants, and the position of a mutation on a protein were then used to prioritize 544 reported mutations based on their ability to impact ZIKV phenotype. Using this criteria, six mutants (representing naturally occurring mutations) were generated as synthetic infectious clones using a 2015 Puerto Rican epidemic strain PRVABC59 as the parental backbone. The phenotypes of these naturally occurring variants were examined using both cell culture and murine model systems. Mutants had distinct phenotypes, including changes in replication rate, embryo death, and decreased head size. In particular, a NS2B mutant previously detected during in vivo studies in rhesus macaques was found to cause lethal infections in adult mice, abortions in pregnant females, and increased viral genome copies in both brain tissue and blood of female mice. Additionally, mutants with changes in the region of NS3 that interfaces with NS5 during replication displayed reduced replication in the blood of adult mice. This analytical pathway, integrating both bioinformatic and wet lab experiments, provides a foundation for understanding how naturally occurring single mutations affect disease outcome and can be used to predict the of severity of future ZIKV outbreaks. To determine if naturally occurring individual mutations in the Zika virus epidemic genotype affect viral virulence or replication rate in vitro or in vivo, we generated an infectious clone representing the epidemic genotype of stain Puerto Rico, 2015. Using this clone, six mutants were created by changing nucleotides in the genome to cause one to two amino acid substitutions in the encoded proteins. The six mutants we generated represent mutations that differentiated the early epidemic genotype from genotypes that were either ancestral or that occurred later in the epidemic. We assayed each mutant for changes in growth rate, and for virulence in adult mice and pregnant mice. Three of the mutants caused catastrophic embryo effects including increased embryonic death or significant decrease in head diameter. Three other mutants that had mutations in a genome region associated with replication resulted in changes in in vitro and in vivo replication rates. These results illustrate the potential impact of individual mutations in viral phenotype.

59 BASIC BIOLOGICAL SCIENCES↗

ILI Code

This R code consists of three scripts, described below. 1. ILI_LHC_sample.R The first script generate 10,000 samples from the total parameter space formed by the ranges of the following five parameters inputted into the ILI model: transmission rate (beta), per capita rate of progress from exposed to infectious state (gamma_1), per capita rate of progress through initial infectious state (gamma_2), per capita rate of progress through hospitalized state (gamma_3), and per capita rate of progress through non-hospitalized infectious state (gamma_4). The output is LHS_samples.csv, for input into the global sensitivity script, ILI_SEIR. 2. ILI_SEIR.R The second script solves a standard Susceptible-Exposed-Infected- Recovered (SEIR) model (a system of Ordinary Differential Equations (ODEs)), runs global sensitivity analyses, and generates plots showing the impact of the input variables on the response variables for each virus. 3. virus_sims.R The third script solves a standard Susceptible-Exposed-Infected- Recovered (SEIR) model (a system of Ordinary Differential Equations (ODEs)), aimed at modeling outbreaks for five common upper respiratory viruses within a contained population. The output of this code is an epidemic curve to show timing and magnitude of the epidemic peak for each virus. Note: for all three scripts, the parameter values must be hard-coded by the user or the output will not be accurate.

Spencer, Julie↗

Characterization of Partially Observed Epidemics - Application to COVID-19

This report documents a statistical method for the "real-time" characterization of partially observed epidemics. Observations consist of daily counts of symptomatic patients, diagnosed with the disease. Characterization, in this context, refers to estimation of epidemiological parameters that can be used to provide short-term forecasts of the ongoing epidemic, as well as to provide gross information for the time-dependent infection rate. The characterization problem is formulated as a Bayesian inverse problem, and is predicated on a model for the distribution of the incubation period. The model parameters are estimated as distributions using a Markov Chain Monte Carlo (MCMC) method, thus quantifying the uncertainty in the estimates. The method is applied to the COVID-19 pandemic of 2020, using data at the country, provincial (e.g., states) and regional (e.g. county) levels. The epidemiological model includes a stochastic component due to uncertainties in the incubation period. This model-form uncertainty is accommodated by a pseudo-marginal Metropolis-Hastings MCMC sampler, which produces posterior distributions that reflect this uncertainty. We approximate the discrepancy between the data and the epidemiological model using Gaussian and negative binomial error models; the latter was motivated by the over-dispersed count data. For small daily counts we find the performance of the calibrated models to be similar for the two error models. For large daily counts the negative-binomial approximation is numerically unstable unlike the Gaussian error model. Application of the model at the country level (for the United States, Germany, Italy, etc.) generally provided accurate forecasts, as the data consisted of large counts which suppressed the day-to-day variations in the observations. Further, the bulk of the data is sourced over the duration before the relaxation of the curbs on population mixing, and is not confounded by any discernible country-wide second wave of infections. At the state-level, where reporting was poor or which evinced few infections (e.g., New Mexico), the variance in the data posed some, though not insurmountable, difficulties, and forecasts were able to capture the data with large uncertainty bounds. The method was found to be sufficiently sensitive to discern the flattening of the infection and epidemic curve due to shelter-in-place orders after around 90% quantile for the incubation distribution (about 10 days for COVID-19). The proposed model was also used at a regional level to compare the forecasts for the central and north-west regions of New Mexico. Modeling the data for these regions illustrated different disease spread dynamics captured by the model. While in the central region the daily counts peaked in the late April, in the north-west region the ramp-up continued for approximately three more weeks.

59 BASIC BIOLOGICAL SCIENCES↗

Data-driven optimized control of the COVID-19 epidemics

Optimizing the impact on the economy of control strategies aiming at containing the spread of COVID-19 is a critical challenge. We use daily new case counts of COVID-19 patients reported by local health administrations from different Metropolitan Statistical Areas (MSAs) within the US to parametrize a model that well describes the propagation of the disease in each area. We then introduce a time-varying control input that represents the level of social distancing imposed on the population of a given area and solve an optimal control problem with the goal of minimizing the impact of social distancing on the economy in the presence of relevant constraints, such as a desired level of suppression for the epidemics at a terminal time. We find that with the exception of the initial time and of the final time, the optimal control input is well approximated by a constant, specific to each area, which contrasts with the implemented system of reopening ‘in phases’. For all the areas considered, this optimal level corresponds to stricter social distancing than the level estimated from data. Proper selection of the time period for application of the control action optimally is important: depending on the particular MSA this period should be either short or long or intermediate. We also consider the case that the transmissibility increases in time (due e.g. to increasingly colder weather), for which we find that the optimal control solution yields progressively stricter measures of social distancing. We finally compute the optimal control solution for a model modified to incorporate the effects of vaccinations on the population and we see that depending on a number of factors, social distancing measures could be optimally reduced during the period over which vaccines are administered to the population.

60 APPLIED LIFE SCIENCES↗

Evaluating disease surveillance strategies for early outbreak detection in contact networks with varying community structure

Disease surveillance systems allow public health agencies to respond to emerging diseases before they become widespread. Developing such systems requires identifying optimal ways to monitor in the context of an epidemic outbreak; this problem is known as sensor selection. Contact networks represent the dynamics of interaction in a population and are used to model how a disease spreads in a population and to explore strategies of sensor selection. We evaluated five sensor selection strategies on their ability to provide an early warning of a COVID-like outbreak in synthetic contact networks encapsulated in four network scenarios. Three of these scenarios assessed different aspects of community structure. The fourth scenario employed a contact network representing the population and interactions of 6.8 million people in New York City, constructed from an agent-based simulation using census and transportation data. This scenario exemplifies how sensor selection strategies may perform in a real-world, urban context. Our findings suggest that the choice of the optimal strategy depends heavily on the community structure of the network. Strategies that select highly connected nodes or maximize network coverage are the optimal surveillance strategy for outbreak detection in many network community structures. However, a naive implementation of these strategies may fail to provide an early warning at all—including in the New York City scenario. Moreover, these methods are impractical for real-world use as they require knowledge of the underlying contact network. Instead, a selection strategy that starts with a set of random nodes and then performs a random walk through a chain of neighbors reliably provides early warnings without requiring prior knowledge of the network. We find this method, called “random chain”, to be the most pragmatic for implementation in a real-world disease surveillance context.

60 APPLIED LIFE SCIENCES↗

Remote Sensing Contributions to Prediction and Risk Assessment of Natural Disasters Caused by Large Scale Rift Valley Fever Outbreaks

Remotely sensed vegetation measurements for the last 30 years combined with other climate data sets such as rainfall and sea surface temperatures have come to play an important role in the study of the ecology of arthropod-borne diseases. We show that epidemics and epizootics of previously unpredictable Rift Valley fever are directly influenced by large scale flooding associated with the El Ni o/Southern Oscillation. This flooding affects the ecology of disease transmitting arthropod vectors through vegetation development and other bioclimatic factors. This information is now utilized to monitor, model, and map areas of potential Rift Valley fever outbreaks and is used as an early warning system for risk reduction of outbreaks to human and animal health, trade, and associated economic impacts. The continuation of such satellite measurements is critical to anticipating, preventing, and managing disease epidemics and epizootics and other climate-related disasters.

Anyamba, Assaf↗

Transient pattern formation in an active matter contact poisoning model

Abstract One of the most notable features in repulsive particle based active matter systems is motility-induced-phase separation (MIPS) where a dense, often crystalline phase and low density fluid coexist. Most active matter studies involve time-dependent activity; however, there are many active systems where individual particles transition from living or moving to dead or nonmotile due to lack of fuel, infection, or poisoning. Here we consider an active matter particle system at densities where MIPS does not occur. When we add a small number of infected particles that can poison other particles, rendering them nonmotile, we find a rich variety of time dependent pattern formation, including MIPS, a wetting phase, and a fragmented state formed when mobile particles plow through a nonmotile packing. We map the patterns as a function of time scaled by epidemic duration, and show that the pattern formation is robust for a wide range of poisoning rates and activity levels. We also show that pattern formation does not occur in a random death model, but requires the promotion of nucleation by contact poisoning. Our results should be relevant to biological and active matter systems where there is some form of poisoning, death, or transition to nonmotility.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗

High Contagiousness and Rapid Spread of Severe Acute Respiratory Syndrome Coronavirus 2

Severe acute respiratory syndrome coronavirus 2 is the causative agent of the ongoing coronavirus disease pandemic. Initial estimates of the early dynamics of the outbreak in Wuhan, China, suggested a doubling time of the number of infected persons of 6–7 days and a basic reproductive number (R 0 ) of 2.2–2.7. We collected extensive individual case reports across China and estimated key epidemiologic parameters, including the incubation period (4.2 days). We then designed 2 mathematical modeling approaches to infer the outbreak dynamics in Wuhan by using high-resolution domestic travel and infection data. Results show that the doubling time early in the epidemic in Wuhan was 2.3–3.3 days. Assuming a serial interval of 6–9 days, we calculated a median R0 value of 5.7 (95% CI 3.8–8.9). Here, we further show that active surveillance, contact tracing, quarantine, and early strong social distancing efforts are needed to stop transmission of the virus.

60 APPLIED LIFE SCIENCES↗

Agent-based Disease Surveillance and Transmission Model

The SARS-CoV-2 pandemic has driven a need for models that can predict transmission among populations and test the effectiveness of proposed interventions to control it such as testing, quarantining, vaccinations, and nonpharmaceutical interventions. Some questions of interest include:1. How rapidly will the virus spread if no action is taken? 2. How frequently should people be tested and quarantined if necessary? 3. Should unvaccinated persons be tested more frequently than the vaccinated? 4. If test results are delayed, how will that affect the spread? 5. How do test false negative rates affect the overall efficacy of testing programs? 6. How do constraints on testing resources impact the overall efficacy of testing programs? 7. How does the patient’s failure to recognize COVID symptoms and quarantine affect the spread? 8. What level of vaccination coverage is needed to suppress the epidemic? 9. What is the risk of a large outbreak (probability exceeding x infections)? 10. What is the cost effectiveness of interventions (dollars per avoided infection)? This report describes the structure of a discrete event simulation model that provides actionable information to address these questions. Parameter inputs and results of analyses have been reported in briefings provided to LLNL management and are not discussed here.

59 BASIC BIOLOGICAL SCIENCES↗

Transmission risk of Oropouche fever across the Americas

Abstract Background Vector-borne diseases (VBDs) are important contributors to the global burden of infectious diseases due to their epidemic potential, which can result in significant population and economic impacts. Oropouche fever, caused by Oropouche virus (OROV), is an understudied zoonotic VBD febrile illness reported in Central and South America. The epidemic potential and areas of likely OROV spread remain unexplored, limiting capacities to improve epidemiological surveillance. Methods To better understand the capacity for spread of OROV, we developed spatial epidemiology models using human outbreaks as OROV transmission-locality data, coupled with high-resolution satellite-derived vegetation phenology. Data were integrated using hypervolume modeling to infer likely areas of OROV transmission and emergence across the Americas. Results Models based on one-support vector machine hypervolumes consistently predicted risk areas for OROV transmission across the tropics of Latin America despite the inclusion of different parameters such as different study areas and environmental predictors. Models estimate that up to 5 million people are at risk of exposure to OROV. Nevertheless, the limited epidemiological data available generates uncertainty in projections. For example, some outbreaks have occurred under climatic conditions outside those where most transmission events occur. The distribution models also revealed that landscape variation, expressed as vegetation loss, is linked to OROV outbreaks. Conclusions Hotspots of OROV transmission risk were detected along the tropics of South America. Vegetation loss might be a driver of Oropouche fever emergence. Modeling based on hypervolumes in spatial epidemiology might be considered an exploratory tool for analyzing data-limited emerging infectious diseases for which little understanding exists on their sylvatic cycles. OROV transmission risk maps can be used to improve surveillance, investigate OROV ecology and epidemiology, and inform early detection.

60 APPLIED LIFE SCIENCES↗

Employing Molecular Phylodynamic Methods to Identify and Forecast HIV Transmission Clusters in Public Health Settings: A Qualitative Study

Molecular HIV surveillance is a promising public health strategy for curbing the HIV epidemic. Clustering technologies used by health departments to date are limited in their ability to infer/forecast cluster growth trajectories. Resolution of the spatiotemporal dynamics of clusters, through phylodynamic and phylogeographic modelling, is one potential strategy to develop a forecasting tool; however, the projected utility of this approach needs assessment. Prior to incorporating novel phylodynamic-based molecular surveillance tools, we sought to identify possible issues related to their feasibility, acceptability, interpretation, and utility. Qualitative data were collected via focus groups among field experts (n = 17, 52.9% female) using semi-structured, open-ended questions. Data were coded using an iterative process, first through the development of provisional themes and subthemes, followed by independent line-by-line coding by two coders. Most participants routinely used molecular methods for HIV surveillance. All agreed that linking molecular sequences to epidemiological data is important for improving HIV surveillance. We found that, in addition to methodological challenges, a variety of implementation barriers are expected in relation to the uptake of phylodynamic methods for HIV surveillance. The participants identified several opportunities to enhance current methods, as well as increase the usability and utility of promising works-in-progress.

59 BASIC BIOLOGICAL SCIENCES↗