Evaluating the performance of Plasmodium falciparum genetic metrics for inferring National Malaria Control Programme reported incidence in Senegal.

BACKGROUND: Genetic surveillance of the Plasmodium falciparum parasite shows great promise for helping National Malaria Control Programmes (NMCPs) assess parasite transmission. Genetic metrics such as the frequency of polygenomic (multiple strain) infections, genetic clones, and the complexity of infection (COI, number of strains per infection) are correlated with transmission intensity. However, despite these correlations, it is unclear whether genetic metrics alone are sufficient to estimate clinical incidence. METHODS: This study examined parasites from 3147 clinical infections sampled between the years 2012-2020 through passive case detection (PCD) across 16 clinic sites spread throughout Senegal. Samples were genotyped with a 24 single nucleotide polymorphism (SNP) molecular barcode that detects parasite strains, distinguishes polygenomic (multiple strain) from monogenomic (single strain) infections, and identifies clonal infections. To determine whether genetic signals can predict incidence, a series of Poisson generalized linear mixed-effects models were constructed to predict the incidence level at each clinical site from a set of genetic metrics designed to measure parasite clonality, superinfection, and co-transmission rates. RESULTS: Model-predicted incidence was compared with the reported standard incidence data determined by the NMCP for each clinic and found that parasite genetic metrics generally correlated with reported incidence, with departures from expected values at very low annual incidence (< 10/1000/annual [‰]). CONCLUSIONS: When transmission is greater than 10 cases per 1000 annual parasite incidence (annual incidence > 10‰), parasite genetics can be used to accurately infer incidence and is consistent with superinfection-based hypotheses of malaria transmission. When transmission was < 10‰, many of the correlations between parasite genetics and incidence were reversed, which may reflect the disproportionate impact of importation and focal transmission on parasite genetics when local transmission levels are low.

Quantifying changes in individual-specific template-based representations of center-of-mass dynamics during walking with ankle exoskeletons using Hybrid-SINDy.

Ankle exoskeletons alter whole-body walking mechanics, energetics, and stability by altering center-of-mass (CoM) motion. Controlling the dynamics governing CoM motion is, therefore, critical for maintaining efficient and stable gait. However, how CoM dynamics change with ankle exoskeletons is unknown, and how to optimally model individual-specific CoM dynamics, especially in individuals with neurological injuries, remains a challenge. Here, we evaluated individual-specific changes in CoM dynamics in unimpaired adults and one individual with post-stroke hemiparesis while walking in shoes-only and with zero-stiffness and high-stiffness passive ankle exoskeletons. To identify optimal sets of physically interpretable mechanisms describing CoM dynamics, termed template signatures, we leveraged hybrid sparse identification of nonlinear dynamics (Hybrid-SINDy), an equation-free data-driven method for inferring sparse hybrid dynamics from a library of candidate functional forms. In unimpaired adults, Hybrid-SINDy automatically identified spring-loaded inverted pendulum-like template signatures, which did not change with exoskeletons (p > 0.16), except for small changes in leg resting length (p < 0.001). Conversely, post-stroke paretic-leg rotary stiffness mechanisms increased by 37-50% with zero-stiffness exoskeletons. While unimpaired CoM dynamics appear robust to passive ankle exoskeletons, how neurological injuries alter exoskeleton impacts on CoM dynamics merits further investigation. Our findings support Hybrid-SINDy's potential to discover mechanisms describing individual-specific CoM dynamics with assistive devices.

Evaluating the performance of Plasmodium falciparum genetics for inferring National Malaria Control Program reported incidence in Senegal.

Genetic surveillance of the Plasmodium falciparum parasite shows great promise for helping National Malaria Control Programs (NMCPs) assess parasite transmission. Genetic metrics such as the frequency of polygenomic (multiple strain) infections, genetic clones, and the complexity of infection (COI, number of strains per infection) are correlated with transmission intensity. However, despite these correlations, it is unclear whether genetic metrics alone are sufficient to estimate clinical incidence. Here, we examined parasites from 3,147 clinical infections sampled between the years 2012-2020 through passive case detection (PCD) across 16 clinic sites spread throughout Senegal. Samples were genotyped with a 24 single nucleotide polymorphism (SNP) molecular barcode that detects parasite strains, distinguishes polygenomic (multiple strain) from monogenomic (single strain) infections, and identifies clonal infections. To determine whether genetic signals can predict incidence, we constructed a series of Poisson generalized linear mixed-effects models to predict the incidence level at each clinical site from a set of genetic metrics designed to measure parasite clonality, superinfection, and co-transmission rates. We compared the model-predicted incidence with the reported standard incidence data determined by the NMCP for each clinic and found that parasite genetic metrics generally correlated with reported incidence, with departures from expected values at very low annual incidence (<10/1000/annual [‰]). When transmission is greater than 10 cases per 1000 annual parasite incidence (annual incidence >10 ‰), parasite genetics can be used to accurately infer incidence and is consistent with superinfection-based hypotheses of malaria transmission. When transmission was <10 ‰, we found that many of the correlations between parasite genetics and incidence were reversed, which we hypothesize reflects the disproportionate impact of importation and focal transmission on parasite genetics when local transmission levels are low.

Malaria surveillance reveals parasite relatedness, signatures of selection, and correlates of transmission across Senegal.

We here analyze data from the first year of an ongoing nationwide program of genetic surveillance of Plasmodium falciparum parasites in Senegal. The analysis is based on 1097 samples collected at health facilities during passive malaria case detection in 2019; it provides a baseline for analyzing parasite genetic metrics as they vary over time and geographic space. The study's goal was to identify genetic metrics that were informative about transmission intensity and other aspects of transmission dynamics, focusing on measures of genetic relatedness between parasites. We found the best genetic proxy for local malaria incidence to be the proportion of polygenomic infections (those with multiple genetically distinct parasites), although this relationship broke down at low incidence. The proportion of related parasites was less correlated with incidence while local genetic diversity was uninformative. The type of relatedness could discriminate local transmission patterns: two nearby areas had similarly high fractions of relatives, but one was dominated by clones and the other by outcrossed relatives. Throughout Senegal, 58% of related parasites belonged to a single network of relatives, within which parasites were enriched for shared haplotypes at known and suspected drug resistance loci and at one novel locus, reflective of ongoing selection pressure.

Sampling for malaria molecular surveillance.

Strategic use of Plasmodium falciparum genetic variation has great potential to inform public health actions for malaria control and elimination. Malaria molecular surveillance (MMS) begins with a strategy to identify and collect parasite samples, guided by public-health priorities. In this review we discuss sampling design practices for MMS and point out epidemiological, biological, and statistical factors that need to be considered. We present examples for different use cases, including detecting emergence and spread of rare variants, establishing transmission sources and inferring changes in malaria transmission intensity. This review will potentially guide the collection of samples and data, serve as a starting point for further methodological innovation, and enhance utilization of MMS to support malaria elimination.

Contraceptive Adoption and Changes in Empowerment in Kenya, Nigeria, and Senegal.

Women's empowerment and contraceptive use are critical to achieving gender equality. The positive association between more empowered women and higher rates of contraceptive use has been well-established by cross-sectional research. However, there remains a gap in understanding the longitudinal relationship between contraceptive adoption and changes to women's empowerment. This study represents a novel approach to understanding the relationship between contraceptive adoption and women's empowerment longitudinally, at the individual level. To the authors' knowledge, this is the first attempt to measure the relationship between contraceptive adoption and women's empowerment using more than one wave of panel data. We leverage the longitudinal design of the Urban Reproductive Health Initiative data to code empowerment items by change over time (e.g., more empowered, no change, less empowered). We use sparse principal component analysis to establish empowerment change domains and calculate individual scores standardized by country-level averages. We estimate mixed effects models on these change domains, to investigate the link between contraceptive adoption and empowerment. We find common themes in empowerment across contexts-but contraceptive adoption has both positive and negative effects on those domains, and this varies across context. We discuss the need for cohort studies to examine this relationship.

Malaria surveillance reveals parasite relatedness, signatures of selection, and correlates of transmission across Senegal.

Parasite genetic surveillance has the potential to play an important role in malaria control. We describe here an analysis of data from the first year of an ongoing, nationwide program of genetic surveillance of Plasmodium falciparum parasites in Senegal, intended to provide actionable information for malaria control efforts. Looking for a good proxy for local malaria incidence, we found that the best predictor was the proportion of polygenomic infections (those with multiple genetically distinct parasites), although that relationship broke down in very low incidence settings (r = 0.77 overall). The proportion of closely related parasites in a site was more weakly correlated ( r = -0.44) with incidence while the local genetic diversity was uninformative. Study of related parasites indicated their potential for discriminating local transmission patterns: two nearby study areas had similarly high fractions of relatives, but one area was dominated by clones and the other by outcrossed relatives. Throughout the country, 58% of related parasites proved to belong to a single network of relatives, within which parasites were enriched for shared haplotypes at known and suspected drug resistance loci as well as at one novel locus, reflective of ongoing selection pressure.

An archetypes approach to malaria intervention impact mapping: a new framework and example application.

BACKGROUND: As both mechanistic and geospatial malaria modeling methods become more integrated into malaria policy decisions, there is increasing demand for strategies that combine these two methods. This paper introduces a novel archetypes-based methodology for generating high-resolution intervention impact maps based on mechanistic model simulations. An example configuration of the framework is described and explored. METHODS: First, dimensionality reduction and clustering techniques were applied to rasterized geospatial environmental and mosquito covariates to find archetypal malaria transmission patterns. Next, mechanistic models were run on a representative site from each archetype to assess intervention impact. Finally, these mechanistic results were reprojected onto each pixel to generate full maps of intervention impact. The example configuration used ERA5 and Malaria Atlas Project covariates, singular value decomposition, k-means clustering, and the Institute for Disease Modeling's EMOD model to explore a range of three-year malaria interventions primarily focused on vector control and case management. RESULTS: Rainfall, temperature, and mosquito abundance layers were clustered into ten transmission archetypes with distinct properties. Example intervention impact curves and maps highlighted archetype-specific variation in efficacy of vector control interventions. A sensitivity analysis showed that the procedure for selecting representative sites to simulate worked well in all but one archetype. CONCLUSION: This paper introduces a novel methodology which combines the richness of spatiotemporal mapping with the rigor of mechanistic modeling to create a multi-purpose infrastructure for answering a broad range of important questions in the malaria policy space. It is flexible and adaptable to a range of input covariates, mechanistic models, and mapping strategies and can be adapted to the modelers' setting of choice.

Prospective surveillance study to detect antimalarial drug resistance, gene deletions of diagnostic relevance and genetic diversity of Plasmodium falciparum in Mozambique: protocol.

INTRODUCTION: Genomic data constitute a valuable adjunct to routine surveillance that can guide programmatic decisions to reduce the burden of infectious diseases. However, genomic capacities remain low in Africa. This study aims to operationalise a functional malaria molecular surveillance system in Mozambique for guiding malaria control and elimination. METHODS AND ANALYSES: This prospective surveillance study seeks to generate Plasmodium falciparum genetic data to (1) monitor molecular markers of drug resistance and deletions in rapid diagnostic test targets; (2) characterise transmission sources in low transmission settings and (3) quantify transmission levels and the effectiveness of antimalarial interventions. The study will take place across 19 districts in nine provinces (Maputo city, Maputo, Gaza, Inhambane, Niassa, Manica, Nampula, Zambézia and Sofala) which span a range of transmission strata, geographies and malaria intervention types. Dried blood spot samples and rapid diagnostic tests will be collected across the study districts in 2022 and 2023 through a combination of dense (all malaria clinical cases) and targeted (a selection of malaria clinical cases) sampling. Pregnant women attending their first antenatal care visit will also be included to assess their value for molecular surveillance. We will use a multiplex amplicon-based next-generation sequencing approach targeting informative single nucleotide polymorphisms, gene deletions and microhaplotypes. Genetic data will be incorporated into epidemiological and transmission models to identify the most informative relationship between genetic features, sources of malaria transmission and programmatic effectiveness of new malaria interventions. Strategic genomic information will be ultimately integrated into the national malaria information and surveillance system to improve the use of the genetic information for programmatic decision-making. ETHICS AND DISSEMINATION: The protocol was reviewed and approved by the institutional (CISM) and national ethics committees of Mozambique (Comité Nacional de Bioética para Saúde) and Spain (Hospital Clinic of Barcelona). Project results will be presented to all stakeholders and published in open-access journals. TRIAL REGISTRATION NUMBER: NCT05306067.

Effect of adolescent pregnancy on child mortality in 46 countries.

INTRODUCTION: Adolescent pregnancy is a known health risk to mother and child. Statements and reports of health outcomes typically group mothers under 20 years old together. Few studies examined this risk at a finer age resolution, none of them comprehensively, and with differing results. METHODS: We analysed Demographic and Health Surveys data from 2004 to 2018 in sub-Saharan Africa (SSA) and South Asia, on firstborn children of mothers 25 years old or younger. We examined the association between maternal age and stillbirths, and neonatal mortality rate (NNMR), infant mortality rate (IMR) and under-5 mortality rate (U5MR), using mixed-effects logistic regression adjusting for major demographic variables and exploring the impact of maternal health-seeking. RESULTS: In both regions and across all endpoints, mortality rates of children born to mothers aged <16 years, 16-17 years and 18-19 years at first birth were about 2-4 times, 1.5-2 times and 1.2-1.5 times higher, respectively, than among firstborn children of mothers aged 23-25. Absolute mortality rates declined over time, but the age gradient remained similar across time periods and regions. Adjusting for rural/urban residence and maternal education, in SSA in 2014-2018 having a <16-year-old mother was associated with ORs of 3.71 (95% CI: 2.50 to 5.51) for stillbirth, 1.92 (1.60-2.30) for NNMR, 2.13 (1.85-2.46) for IMR and 2.39 (2.13-2.68) for U5MR, compared with having a mother aged 23-25. In South Asia, in 2014-2018 ORs were 5.12 (2.85-9.20) for stillbirth, 2.46 (2.03-2.97) for NNMR, 2.62 (2.22-3.08) for IMR and 2.59 (2.22-3.03) for U5MR. Part of the effect on NNMR and IMR may be mediated by a lower maternal health-seeking rate. CONCLUSIONS: Adolescent pregnancy is associated with dramatically worse child survival and mitigated by health-seeking behaviour, likely reflecting a combination of biological and social factors. Refining maternal age reporting will avoid masking the increased risk to children born to very young adolescent mothers. Collection of additional biological and social data may better reveal mediators of this relationship. Targeted intervention strategies to reduce unintended pregnancy at earlier ages may also improve child survival.

Evaluating COVID-19 reporting data in the context of testing strategies across 31 low- and middle-income countries.

BACKGROUND: The case count for coronavirus disease 2019 (COVID-19) is the predominant measure used to track epidemiological dynamics and inform policy decision-making. Case counts, however, are influenced by testing rates and strategies, which have varied over time and space. A method to interpret COVID-19 case counts consistently in the context of other surveillance data is needed, especially for data-limited settings in low- and middle-income countries (LMICs). METHODS: Statistical analyses were used to detect changes in COVID-19 surveillance data. The pruned exact linear time change detection method was applied for COVID-19 case counts, number of tests, and test positivity rate over time. With this information, change points were categorized as likely driven by epidemiological dynamics or non-epidemiological influences, such as noise. FINDINGS: Higher rates of epidemiological change detection are more associated with open testing policies than with higher testing rates. This study quantified alignment of non-pharmaceutical interventions with epidemiological changes. LMICs have the testing capacity to measure prevalence with precision if they use randomized testing. Rwanda stands out as a country with an efficient COVID-19 surveillance system. Subnational data reveal heterogeneity in epidemiological dynamics and surveillance. INTERPRETATION: Relying solely on case counts to interpret pandemic dynamics has important limitations. Normalizing counts by testing rate mitigates some of these limitations, and an open testing policy is key to efficient surveillance. The study findings can be leveraged by public health officials to strengthen COVID-19 surveillance and support programmatic decision-making.

Linked surveillance and genetic data uncovers programmatically relevant geographic scale of Guinea worm transmission in Chad.

BACKGROUND: Guinea worm (Dracunculus medinensis) was detected in Chad in 2010 after a supposed ten-year absence, posing a challenge to the global eradication effort. Initiation of a village-based surveillance system in 2012 revealed a substantial number of dogs infected with Guinea worm, raising questions about paratenic hosts and cross-species transmission. METHODOLOGY/PRINCIPAL FINDINGS: We coupled genomic and surveillance case data from 2012-2018 to investigate the modes of transmission between dog and human hosts and the geographic connectivity of worms. Eighty-six variants across four genes in the mitochondrial genome identified 41 genetically distinct worm genotypes. Spatiotemporal modeling revealed worms with the same genotype ('genetically identical') were within a median range of 18.6 kilometers of each other, but largely within approximately 50 kilometers. Genetically identical worms varied in their degree of spatial clustering, suggesting there may be different factors that favor or constrain transmission. Each worm was surrounded by five to ten genetically distinct worms within a 50 kilometer radius. As expected, we observed a change in the genetic similarity distribution between pairs of worms using variants across the complete mitochondrial genome in an independent population. CONCLUSIONS/SIGNIFICANCE: In the largest study linking genetic and surveillance data to date of Guinea worm cases in Chad, we show genetic identity and modeling can facilitate the understanding of local transmission. The co-occurrence of genetically non-identical worms in quantitatively identified transmission ranges highlights the necessity for genomic tools to link cases. The improved discrimination between pairs of worms from variants identified across the complete mitochondrial genome suggests that expanding the number of genomic markers could link cases at a finer scale. These results suggest that scaling up genomic surveillance for Guinea worm may provide additional value for programmatic decision-making critical for monitoring cases and intervention efficacy to achieve elimination.

A modular approach to integrating multiple data sources into real-time clinical prediction for pediatric diarrhea.

Traditional clinical prediction models focus on parameters of the individual patient. For infectious diseases, sources external to the patient, including characteristics of prior patients and seasonal factors, may improve predictive performance. We describe the development of a predictive model that integrates multiple sources of data in a principled statistical framework using a post-test odds formulation. Our method enables electronic real-time updating and flexibility, such that components can be included or excluded according to data availability. We apply this method to the prediction of etiology of pediatric diarrhea, where 'pre-test' epidemiologic data may be highly informative. Diarrhea has a high burden in low-resource settings, and antibiotics are often over-prescribed. We demonstrate that our integrative method outperforms traditional prediction in accurately identifying cases with a viral etiology, and show that its clinical application, especially when used with an additional diagnostic test, could result in a 61% reduction in inappropriately prescribed antibiotics.

Insights into population behavior during the COVID-19 pandemic from cell phone mobility data and manifold learning.

Understanding the complex interplay between human behavior, disease transmission and non-pharmaceutical interventions during the COVID-19 pandemic could provide valuable insights with which to focus future public health efforts. Cell phone mobility data offer a modern measurement instrument to investigate human mobility and behavior at an unprecedented scale. We investigate aggregated and anonymized mobility data, which measure how populations at the census-block-group geographic scale stayed at home in California, Georgia, Texas and Washington from the beginning of the pandemic. Using manifold learning techniques, we show that a low-dimensional embedding enables the identification of patterns of mobility behavior that align with stay-at-home orders, correlate with socioeconomic factors, cluster geographically, reveal subpopulations that probably migrated out of urban areas and, importantly, link to COVID-19 case counts. The analysis and approach provide local epidemiologists a framework for interpreting mobility data and behavior to inform policy makers' decision-making aimed at curbing the spread of COVID-19.

Tracking progress towards malaria elimination in China: Individual-level estimates of transmission and its spatiotemporal variation using a diffusion network approach.

In order to monitor progress towards malaria elimination, it is crucial to be able to measure changes in spatio-temporal transmission. However, common metrics of malaria transmission such as parasite prevalence are under powered in elimination contexts. China has achieved major reductions in malaria incidence and is on track to eliminate, having reporting zero locally-acquired malaria cases in 2017 and 2018. Understanding the spatio-temporal pattern underlying this decline, especially the relationship between locally-acquired and imported cases, can inform efforts to maintain elimination and prevent re-emergence. This is particularly pertinent in Yunnan province, where the potential for local transmission is highest. Using a geo-located individual-level dataset of cases recorded in Yunnan province between 2011 and 2016, we introduce a novel Bayesian framework to model a latent diffusion process and estimate the joint likelihood of transmission between cases and the number of cases with unobserved sources of infection. This is used to estimate the case reproduction number, Rc. We use these estimates within spatio-temporal geostatistical models to map how transmission varied over time and space, estimate the timeline to elimination and the risk of resurgence. We estimate the mean Rc between 2011 and 2016 to be 0.171 (95% CI = 0.165, 0.178) for P. vivax cases and 0.089 (95% CI = 0.076, 0.103) for P. falciparum cases. From 2014 onwards, no cases were estimated to have a Rc value above one. An unobserved source of infection was estimated to be moderately likely (p>0.5) for 19/ 611 cases and high (p>0.8) for 2 cases, suggesting very high levels of case ascertainment. Our estimates suggest that, maintaining current intervention efforts, Yunnan is unlikely to experience sustained local transmission up to 2020. However, even with a mean of 0.005 projected up to 2020, locally-acquired cases are possible due to high levels of importation.

The seasonality of diarrheal pathogens: A retrospective study of seven sites over three years.

BACKGROUND: Pediatric diarrhea can be caused by a wide variety of pathogens, from bacteria to viruses to protozoa. Pathogen prevalence is often described as seasonal, peaking annually and associated with specific weather conditions. Although many studies have described the seasonality of diarrheal disease, these studies have occurred predominantly in temperate regions. In tropical and resource-constrained settings, where nearly all diarrhea-associated mortality occurs, the seasonality of many diarrheal pathogens has not been well characterized. As a retrospective study, we analyze the seasonal prevalence of diarrheal pathogens among children with moderate-to-severe diarrhea (MSD) over three years from the seven sites of the Global Enteric Multicenter Study (GEMS), a case-control study. Using data from this expansive study on diarrheal disease, we characterize the seasonality of different pathogens, their association with site-specific weather patterns, and consistency across study sites. METHODOLOGY/PRINCIPAL FINDINGS: Using traditional methodologies from signal processing, we found that certain pathogens peaked at the same time every year, but not at all sites. We also found associations between pathogen prevalence and weather or "seasons," which are defined by applying modern machine-learning methodologies to site-specific weather data. In general, rotavirus was most prevalent during the drier "winter" months and out of phase with bacterial pathogens, which peaked during hotter and rainier times of year corresponding to "monsoon," "rainy," or "summer" seasons. CONCLUSIONS/SIGNIFICANCE: Identifying the seasonally-dependent prevalence for diarrheal pathogens helps characterize the local epidemiology and inform the clinical diagnosis of symptomatic children. Our multi-site, multi-continent study indicates a complex epidemiology of pathogens that does not reveal an easy generalization that is consistent across all sites. Instead, our study indicates the necessity of local data to characterizing the epidemiology of diarrheal disease. Recognition of the local associations between weather conditions and pathogen prevalence suggests transmission pathways and could inform control strategies in these settings.

Sub-national levels and trends in contraceptive prevalence, unmet need, and demand for family planning in Nigeria with survey uncertainty.

BACKGROUND: Ambitious global goals have been established to provide universal access to affordable modern contraceptive methods. To measure progress toward such goals in populous countries like Nigeria, it's essential to characterize the current levels and trends of family planning (FP) indicators such as unmet need and modern contraceptive prevalence rates (mCPR). Moreover, the substantial heterogeneity across Nigeria and scale of programmatic implementation requires a sub-national resolution of these FP indicators. The aim of this study is to estimate the levels and trends of FP indicators at a subnational scale in Nigeria utilizing all available data and accounting for survey design and uncertainty. METHODS: We utilized all available cross-sectional survey data from Nigeria including the Demographic and Health Surveys, Multiple Indicator Cluster Surveys, National Nutrition and Health Surveys, and Performance, Monitoring, and Accountability 2020. We developed a hierarchical Bayesian model that incorporates all of the individual level data from each survey instrument, accounts for survey uncertainty, leverages spatio-temporal smoothing, and produces probabilistic estimates with uncertainty intervals. RESULTS: We estimate that overall rates and trends of mCPR and unmet need have remained low in Nigeria: the average annual rate of change for mCPR by state is 0.5% (0.4%,0.6%) from 2012-2017. Unmet need by age-parity demographic groups varied significantly across Nigeria; parous women express much higher rates of unmet need than nulliparous women. CONCLUSIONS: Understanding the estimates and trends of FP indicators at a subnational resolution in Nigeria is integral to inform programmatic decision-making. We identify age-parity-state subgroups with large rates of unmet need. We also find conflicting trends by survey instrument across a number of states. Our model-based estimates highlight these inconsistencies, attempt to reconcile the direct survey estimates, and provide uncertainty intervals to enable interpretation of model and survey estimates for decision-making.

Identifying spatio-temporal dynamics of Ebola in Sierra Leone using virus genomes.

Containing the recent West African outbreak of Ebola virus (EBOV) required the deployment of substantial global resources. Despite recent progress in analysing and modelling EBOV epidemiological data, a complete characterization of the spatio-temporal spread of Ebola cases remains a challenge. In this work, we offer a novel perspective on the EBOV epidemic in Sierra Leone that uses individual virus genome sequences to inform population-level, spatial models. Calibrated to phylogenetic linkages of virus genomes, these spatial models provide unique insight into the disease mobility of EBOV in Sierra Leone without the need for human mobility data. Consistent with other investigations, our results show that the spread of EBOV during the beginning and middle portions of the epidemic strongly depended on the size of and distance between populations. Our phylodynamic analysis also revealed a change in model preference towards a spatial model with power-law characteristics in the latter portion of the epidemic, correlated with the timing of major intervention campaigns. More generally, we believe this framework, pairing molecular diagnostics with a dynamic model selection procedure, has the potential to be a powerful forecasting tool along with offering operationally relevant guidance for surveillance and sampling strategies during an epidemic.

Chaos as an intermittently forced linear system.

Understanding the interplay of order and disorder in chaos is a central challenge in modern quantitative science. Approximate linear representations of nonlinear dynamics have long been sought, driving considerable interest in Koopman theory. We present a universal, data-driven decomposition of chaos as an intermittently forced linear system. This work combines delay embedding and Koopman theory to decompose chaotic dynamics into a linear model in the leading delay coordinates with forcing by low-energy delay coordinates; this is called the Hankel alternative view of Koopman (HAVOK) analysis. This analysis is applied to the Lorenz system and real-world examples including Earth's magnetic field reversal and measles outbreaks. In each case, forcing statistics are non-Gaussian, with long tails corresponding to rare intermittent forcing that precedes switching and bursting phenomena. The forcing activity demarcates coherent phase space regions where the dynamics are approximately linear from those that are strongly nonlinear.The huge amount of data generated in fields like neuroscience or finance calls for effective strategies that mine data to reveal underlying dynamics. Here Brunton et al.develop a data-driven technique to analyze chaotic systems and predict their dynamics in terms of a forced linear model.

Data-driven discovery of partial differential equations.

We propose a sparse regression method capable of discovering the governing partial differential equation(s) of a given system by time series measurements in the spatial domain. The regression framework relies on sparsity-promoting techniques to select the nonlinear and partial derivative terms of the governing equations that most accurately represent the data, bypassing a combinatorially large search through all possible candidate models. The method balances model complexity and regression accuracy by selecting a parsimonious model via Pareto analysis. Time series measurements can be made in an Eulerian framework, where the sensors are fixed spatially, or in a Lagrangian framework, where the sensors move with the dynamics. The method is computationally efficient, robust, and demonstrated to work on a variety of canonical problems spanning a number of scientific domains including Navier-Stokes, the quantum harmonic oscillator, and the diffusion equation. Moreover, the method is capable of disambiguating between potentially nonunique dynamical terms by using multiple time series taken with different initial data. Thus, for a traveling wave, the method can distinguish between a linear wave equation and the Korteweg-de Vries equation, for instance. The method provides a promising new technique for discovering governing equations and physical laws in parameterized spatiotemporal systems, where first-principles derivations are intractable.