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.

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.

Alternative approaches for creating a wealth index: the case of Mozambique.

INTRODUCTION: The wealth index is widely used as a proxy for a household's socioeconomic position (SEP) and living standard. This work constructs a wealth index for the Mopeia district in Mozambique using data collected in year 2021 under the BOHEMIA (Broad One Health Endectocide-based Malaria Intervention in Africa) project. METHODS: We evaluate the performance of three alternative approaches against the Demographic and Health Survey (DHS) method based wealth index: feature selection principal components analysis (PCA), sparse PCA and robust PCA. The internal coherence between four wealth indices is investigated through statistical testing. Validation and an evaluation of the stability of the wealth index are performed with additional household income data from the BOHEMIA Health Economics Survey and the 2018 Malaria Indicator Survey data in Mozambique. RESULTS: The Spearman's rank correlation between wealth index ventiles from four methods is over 0.98, indicating a high consistency in results across methods. Wealth rankings and households' income show a strong concordance with the area under the curve value of ~0.7 in the receiver operating characteristic analysis. The agreement between the alternative wealth indices and the DHS wealth index demonstrates the stability in rankings from the alternative methods. CONCLUSIONS: This study creates a wealth index for Mopeia, Mozambique, and shows that DHS method based wealth index is an appropriate proxy for the SEP in low-income regions. However, this research recommends feature selection PCA over the DHS method since it uses fewer asset indicators and constructs a high-quality wealth index.

Alternative approaches for creating a wealth index: the case of Mozambique

Background Residual malaria transmission is the result of adaptive mosquito behavior that allows malaria vectors to thrive and sustain transmission in the presence of good access to bed nets or insecticide residual spraying. These behaviors include crepuscular and outdoor feeding as well as intermittent feeding upon livestock. Ivermectin is a broadly used antiparasitic drug that kills mosquitoes feeding on a treated subject for a dose-dependent period. Mass drug administration with ivermectin has been proposed as a complementary strategy to reduce malaria transmission. Methods A cluster randomized, parallel arm, superiority trial conducted in two settings with distinct eco-epidemio logical conditions in East and Southern Africa. There will be three groups: human intervention, consisting of a dose of ivermectin (400 mcg/kg) administered monthly for 3 months to all the eligible population in the cluster (>15 kg, nonpregnant and no medical contraindication); human and livestock intervention, consisting human treatment as above plus treatment of livestock in the area with a single dose of injectable ivermectin (200 mcg/kg) monthly for 3 months; and controls, consisting of a dose of albendazole (400 mg) monthly for 3 months. The main outcome measure will be malaria incidence in a cohort of children under fve living in the core of each cluster followed prospectively with monthly RDTs Discussion The second site for the implementation of this protocol has changed from Tanzania to Kenya. This sum mary presents the Mozambique-specifc protocol while the updated master protocol and the adapted Kenya-specifc

BOHEMIA a cluster randomized trial to assess the impact of an endectocide-based one health approach to malaria in Mozambique: baseline demographics and key malaria indicators.

BACKGROUND: Many geographical areas of sub-Saharan Africa, especially in rural settings, lack complete and up-to-date demographic data, posing a challenge for implementation and evaluation of public health interventions and carrying out large-scale health research. A demographic survey was completed in Mopeia district, located in the Zambezia province in Mozambique, to inform the Broad One Health Endectocide-based Malaria Intervention in Africa (BOHEMIA) cluster randomized clinical trial, which tested ivermectin mass drug administration to humans and/or livestock as a potential novel strategy to decrease malaria transmission. METHODS: The demographic survey was a prospective descriptive study, which collected data of all the households in the district that accepted to participate. Households were mapped through geolocation and identified with a unique identification number. Basic demographic data of the household members was collected and each person received a permanent identification number for the study. RESULTS: 25,550 households were mapped and underwent the demographic survey, and 131,818 individuals were registered in the district. The average household size was 5 members and 76.9% of households identified a male household head. Housing conditions are often substandard with low access to improved water systems and electricity. The reported coverage of malaria interventions was 71.1% for indoor residual spraying and 54.1% for universal coverage of long-lasting insecticidal nets. The median age of the population was 15 years old. There were 910 deaths in the previous 12 months reported, and 43.9% were of children less than 5 years of age. CONCLUSIONS: The study showed that the district had good coverage of vector control tools against malaria but sub-optimal living conditions and poor access to basic services. The majority of households are led by males and Mopeia Sede/Cuacua is the most populated locality in the district. The population of Mopeia is young (< 15 years) and there is a high childhood mortality. The results of this survey were crucial as they provided the household and population profiles and allowed the design and implementation of the cluster randomized clinical trial. Trial registration NCT04966702.

BOHEMIA a cluster randomized trial to assess the impact of an endectocide-based one health approach to malaria in Mozambique: baseline demographics and key malaria indicators

Many geographical areas of sub-Saharan Africa, especially in rural settings, lack complete and up-to-date demographic data, posing a challenge for implementation and evaluation of public health interventions and carrying out large-scale health research. A demographic survey was completed in Mopeia district, located in the Zambezia province in Mozambique, to inform the Broad One Health Endectocide-based Malaria Intervention in Africa (BOHEMIA) cluster randomized clinical trial, which tested ivermectin mass drug administration to humans and/or livestock as a potential novel strategy to decrease malaria transmission. Methods: The demographic survey was a prospective descriptive study, which collected data of all the households in the district that accepted to participate. Households were mapped through geolocation and identified with a unique identification number. Basic demographic data of the household members was collected and each person received a permanent identification number for the study. Results: 25,550 households were mapped and underwent the demographic survey, and 131,818 individuals were registered in the district. The average household size was 5 members and 76.9% of households identified a male household head. Housing conditions are often substandard with low access to improved water systems and electricity. The reported coverage of malaria interventions was 71.1% for indoor residual spraying and 54.1% for universal coverage of long-lasting insecticidal nets. The median age of the population was 15 years old. There were 910 deaths in the previous 12 months reported, and 43.9% were of children less than 5 years of age. Conclusions: The study showed that the district had good coverage of vector control tools against malaria but sub-optimal living conditions and poor access to basic services. The majority of households are led by males and Mopeia Sede/Cuacua is the most populated locality in the district. The population of Mopeia is young (< 15 years) and there is a high childhood mortality. The results of this survey were crucial as they provided the household and population profiles and allowed the design and implementation of the cluster randomized clinical trial. Trial registration NCT04966702.

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.

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.

BOHEMIA: Broad One Health Endectocide-based Malaria Intervention in Africa-a phase III cluster-randomized, open-label, clinical trial to study the safety and efficacy of ivermectin mass drug administration to reduce malaria transmission in two African settings.

BACKGROUND: Residual malaria transmission is the result of adaptive mosquito behavior that allows malaria vectors to thrive and sustain transmission in the presence of good access to bed nets or insecticide residual spraying. These behaviors include crepuscular and outdoor feeding as well as intermittent feeding upon livestock. Ivermectin is a broadly used antiparasitic drug that kills mosquitoes feeding on a treated subject for a dose-dependent period. Mass drug administration with ivermectin has been proposed as a complementary strategy to reduce malaria transmission. METHODS: A cluster randomized, parallel arm, superiority trial conducted in two settings with distinct eco-epidemiological conditions in East and Southern Africa. There will be three groups: human intervention, consisting of a dose of ivermectin (400 mcg/kg) administered monthly for 3 months to all the eligible population in the cluster (>15 kg, non-pregnant and no medical contraindication); human and livestock intervention, consisting human treatment as above plus treatment of livestock in the area with a single dose of injectable ivermectin (200 mcg/kg) monthly for 3 months; and controls, consisting of a dose of albendazole (400 mg) monthly for 3 months. The main outcome measure will be malaria incidence in a cohort of children under five living in the core of each cluster followed prospectively with monthly RDTs DISCUSSION: The second site for the implementation of this protocol has changed from Tanzania to Kenya. This summary presents the Mozambique-specific protocol while the updated master protocol and the adapted Kenya-specific protocol undergo national approval in Kenya. BOHEMIA will be the first large-scale trial evaluating the impact of ivermectin-only mass drug administration to humans or humans and cattle on local malaria transmission TRIAL REGISTRATION: ClinicalTrials.gov NCT04966702 . Registered on July 19, 2021. Pan African Clinical Trials Registry PACTR202106695877303.

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.

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.

Potential impact of 5 years of ivermectin mass drug administration on malaria outcomes in high burden countries.

INTRODUCTION: The global progress against malaria has slowed significantly since 2017. As the current malaria control tools seem insufficient to get the trend back on track, several clinical trials are investigating ivermectin mass drug administration (iMDA) as a potential additional vector control tool; however, the health impacts and cost-effectiveness of this new strategy remain unclear. METHODS: We developed an analytical tool based on a full factorial experimental design to assess the potential impact of iMDA in nine high burden sub-Saharan African countries. The simulated iMDA regimen was assumed to be delivered monthly to the targeted population for 3 months each year from 2023 to 2027. A broad set of parameters of ivermectin efficacy, uptake levels and global intervention scenarios were used to predict averted malaria cases and deaths. We then explored the potential averted treatment costs, expected implementation costs and cost-effectiveness ratios under different scenarios. RESULTS: In the scenario where coverage of malaria interventions was maintained at 2018 levels, we found that iMDA in these nine countries has the potential to reverse the predicted growth of malaria burden by averting 20-50 million cases and 36 000-90 000 deaths with an assumed efficacy of 20%. If iMDA has an efficacy of 40%, we predict between 40-99 million cases and 73 000-179 000 deaths will be averted with an estimated net cost per case averted between US$2 and US$7, and net cost per death averted between US$1460 and US$4374. CONCLUSION: This study measures the potential of iMDA to reverse the increasing number of malaria cases for several sub-Saharan African countries. With additional efficacy information from ongoing clinical trials and country-level modifications, our analytical tool can help determine the appropriate uptake strategies of iMDA by calculating potential marginal gains and costs under different scenarios.

Epidemiological and economic impact of COVID-19 in the US.

This research measures the epidemiological and economic impact of COVID-19 spread in the US under different mitigation scenarios, comprising of non-pharmaceutical interventions. A detailed disease model of COVID-19 is combined with a model of the US economy to estimate the direct impact of labor supply shock to each sector arising from morbidity, mortality, and lockdown, as well as the indirect impact caused by the interdependencies between sectors. During a lockdown, estimates of jobs that are workable from home in each sector are used to modify the shock to labor supply. Results show trade-offs between economic losses, and lives saved and infections averted are non-linear in compliance to social distancing and the duration of the lockdown. Sectors that are worst hit are not the labor-intensive sectors such as the Agriculture sector and the Construction sector, but the ones with high valued jobs such as the Professional Services, even after the teleworkability of jobs is accounted for. Additionally, the findings show that a low compliance to interventions can be overcome by a longer shutdown period and vice versa to arrive at similar epidemiological impact but their net effect on economic loss depends on the interplay between the marginal gains from averting infections and deaths, versus the marginal loss from having healthy workers stay at home during the shutdown.

Differential Impact of Social Distancing on COVID-19 Spread in the U.S.: By Rurality and Social Vulnerability.

Background: To quantify lessons learned to better prepare for similar pandemic crisis in the future, we assess the overall impact of social distancing on the daily growth rate of COVID-19 infections in the U.S. during the initial phase of the pandemic and the impacts' heterogeneity by urbanity and social vulnerability of the counties. The initial phase is chosen to purposely identify the essential and largest impact of the first-line of defense measure for similar pandemic: social distancing. Methods: Spatial Durbin models with county fixed effects were used to account for spatial dependencies and identify spatial spillover effects and spatial heterogeneity. Results: Besides the substantial curve flattening effects of social distancing, our results show significant spillover effects induced by neighboring counties' social distancing levels even in the absence of significant within-county effects. Urban and areas with high social vulnerability are the ones benefit the most from social distancing and high level of compliance is needed. Moderate level is enough in reaching the peak marginal impact in rural and areas with low social vulnerability.

Prioritizing allocation of COVID-19 vaccines based on social contacts increases vaccination effectiveness.

We study allocation of COVID-19 vaccines to individuals based on the structural properties of their underlying social contact network. Even optimistic estimates suggest that most countries will likely take 6 to 24 months to vaccinate their citizens. These time estimates and the emergence of new viral strains urge us to find quick and effective ways to allocate the vaccines and contain the pandemic. While current approaches use combinations of age-based and occupation-based prioritizations, our strategy marks a departure from such largely aggregate vaccine allocation strategies. We propose a novel approach motivated by recent advances in (i) science of real-world networks that point to efficacy of certain vaccination strategies and (ii) digital technologies that improve our ability to estimate some of these structural properties. Using a realistic representation of a social contact network for the Commonwealth of Virginia, combined with accurate surveillance data on spatiotemporal cases and currently accepted models of within- and between-host disease dynamics, we study how a limited number of vaccine doses can be strategically distributed to individuals to reduce the overall burden of the pandemic. We show that allocation of vaccines based on individuals' degree (number of social contacts) and total social proximity time is significantly more effective than the currently used age-based allocation strategy in terms of number of infections, hospitalizations and deaths. Our results suggest that in just two months, by March 31, 2021, compared to age-based allocation, the proposed degree-based strategy can result in reducing an additional 56-110k infections, 3.2- 5.4k hospitalizations, and 700-900 deaths just in the Commonwealth of Virginia. Extrapolating these results for the entire US, this strategy can lead to 3-6 million fewer infections, 181-306k fewer hospitalizations, and 51-62k fewer deaths compared to age-based allocation. The overall strategy is robust even: (i) if the social contacts are not estimated correctly; (ii) if the vaccine efficacy is lower than expected or only a single dose is given; (iii) if there is a delay in vaccine production and deployment; and (iv) whether or not non-pharmaceutical interventions continue as vaccines are deployed. For reasons of implementability, we have used degree, which is a simple structural measure and can be easily estimated using several methods, including the digital technology available today. These results are significant, especially for resource-poor countries, where vaccines are less available, have lower efficacy, and are more slowly distributed.

Epidemiological and Economic Impact of COVID-19 in the US.

This research measures the epidemiological and economic impact of COVID-19 spread in the US under different mitigation scenarios, comprising of non-pharmaceutical interventions. A detailed disease model of COVID-19 is combined with a model of the US economy to estimate the direct impact of labor supply shock to each sector arising from morbidity, mortality, and lock down, as well as the indirect impact caused by the interdependencies between sectors. During a lockdown, estimates of jobs that are workable from home in each sector are used to modify the shock to labor supply. Results show trade-offs between economic losses, and lives saved and infections averted are non-linear in compliance to social distancing and the duration of lockdown. Sectors that are worst hit are not the labor-intensive sectors such as Agriculture and Construction, but the ones with high valued jobs such as Professional Services, even after the teleworkability of jobs is accounted for. Additionally, the findings show that a low compliance to interventions can be overcome by a longer shutdown period and vice versa to arrive at similar epidemiological impact but their net effect on economic loss depends on the interplay between the marginal gains from averting infections and deaths, versus the marginal loss from having healthy workers stay at home during the shutdown.

Medical costs of keeping the US economy open during COVID-19.

We use an individual based model and national level epidemic simulations to estimate the medical costs of keeping the US economy open during COVID-19 pandemic under different counterfactual scenarios. We model an unmitigated scenario and 12 mitigation scenarios which differ in compliance behavior to social distancing strategies and in the duration of the stay-home order. Under each scenario we estimate the number of people who are likely to get infected and require medical attention, hospitalization, and ventilators. Given the per capita medical cost for each of these health states, we compute the total medical costs for each scenario and show the tradeoffs between deaths, costs, infections, compliance and the duration of stay-home order. We also consider the hospital bed capacity of each Hospital Referral Region (HRR) in the US to estimate the deficit in beds each HRR will likely encounter given the demand for hospital beds. We consider a case where HRRs share hospital beds among the neighboring HRRs during a surge in demand beyond the available beds and the impact it has in controlling additional deaths.

Medical Costs of Keeping the US Economy Open During COVID-19.

We use an individual based model and national level epidemic simulations to estimate the medical costs of keeping the US economy open during COVID-19 pandemic under different counterfactual scenarios. We model an unmitigated scenario and 12 mitigation scenarios which differ in compliance behavior to social distancing strategies and to the duration of the stay-home order. Under each scenario we estimate the number of people who are likely to get infected and require medical attention, hospitalization, and ventilators. Given the per capita medical cost for each of these health states, we compute the total medical costs for each scenario and show the tradeoffs between deaths, costs, infections, compliance and the duration of stay-home order. We also consider the hospital bed capacity of each Hospital Referral Region (HRR) in the US to estimate the deficit in beds each HRR will likely encounter given the demand for hospital beds. We consider a case where HRRs share hospital beds among the neighboring HRRs during a surge in demand beyond the available beds and the impact it has in controlling additional deaths.

An Active Learning Method for the Comparison of Agent-based Models.

We develop a methodology for comparing two or more agent-based models that are developed for the same domain, but may differ in the particular 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 transition boundaries in contagion processes in order to compare two agent-based models of rooftop solar panel adoption.