Category: Publications

  • Using Multiple Scale Spatio-Temporal Patterns for Validating Spatially Explicit Agent-Based Models

    Kang JY, Aldstadt J

    Int J Geogr Inf Sci 2019;33(1):193-213

    PMID: 31695574

    Abstract

    Spatially explicit agent-based models (ABMs) have been widely utilized to simulate the dynamics of spatial processes that involve the interactions of individual agents. The assumptions embedded in the ABMs may be responsible for uncertainty in the model outcomes. To ensure the reliability of the outcomes in terms of their space-time patterns, model validation should be performed. In this paper, we propose the use of multiple scale spatio-temporal patterns for validating spatially explicit ABMs. We evaluated several specifications of vector-borne disease transmission models by comparing space-time patterns of model outcomes to observations at multiple scales via the sum of root mean square error (RMSE) measurement. The results indicate that specifications of the spatial configurations of residential area and immunity status of individual humans are of importance to reproduce observed patterns of dengue outbreaks at multiple space-time scales. Our approach to using multiple scale spatio-temporal patterns can help not only to understand the dynamic associations between model specifications and model outcomes, but also to validate spatially explicit ABMs.

  • Use of structural equation models to predict dengue illness phenotype

    Park S, Srikiatkhachorn A, Kalayanarooj S, Macareo L, Green S, Friedman JF, Rothman AL

    PLoS Negl Trop Dis 2018 Oct;12(10):e0006799

    PMID: 30273334

    Abstract

    BACKGROUND: Early recognition of dengue, particularly patients at risk for plasma leakage, is important to clinical management. The objective of this study was to build predictive models for dengue, dengue hemorrhagic fever (DHF), and dengue shock syndrome (DSS) using structural equation modelling (SEM), a statistical method that evaluates mechanistic pathways.

    METHODS/FINDINGS: We performed SEM using data from 257 Thai children enrolled within 72 h of febrile illness onset, 156 with dengue and 101 with non-dengue febrile illnesses. Models for dengue, DHF, and DSS were developed based on data obtained three and one day(s) prior to fever resolution (fever days -3 and -1, respectively). Models were validated using data from 897 subjects who were not used for model development. Predictors for dengue and DSS included age, tourniquet test, aspartate aminotransferase, and white blood cell, % lymphocytes, and platelet counts. Predictors for DHF included age, aspartate aminotransferase, hematocrit, tourniquet test, and white blood cell and platelet counts. The models showed good predictive performances in the validation set, with area under the receiver operating characteristic curves (AUC) at fever day -3 of 0.84, 0.67, and 0.70 for prediction of dengue, DHF, and DSS, respectively. Predictive performance was comparable using data based on the timing relative to enrollment or illness onset, and improved closer to the critical phase (AUC 0.73 to 0.94, 0.61 to 0.93, and 0.70 to 0.96 for dengue, DHF, and DSS, respectively).

    CONCLUSIONS: Predictive models developed using SEM have potential use in guiding clinical management of suspected dengue prior to the critical phase of illness.

  • Reconstruction of antibody dynamics and infection histories to evaluate dengue risk

    Salje H, Cummings DAT, Rodriguez-Barraquer I, Katzelnick LC, Lessler J, Klungthong C, Thaisomboonsuk B, Nisalak A, Weg A, Ellison D, Macareo L, Yoon IK, Jarman R, Thomas S, Rothman AL, Endy T, Cauchemez S

    Nature 2018 May;557(7707):719-723

    PMID: 29795354

    Abstract

    As with many pathogens, most dengue infections are subclinical and therefore unobserved . Coupled with limited understanding of the dynamic behaviour of potential serological markers of infection, this observational problem has wide-ranging implications, including hampering our understanding of individual- and population-level correlates of infection and disease risk and how these change over time, between assay interpretations and with cohort design. Here we develop a framework that simultaneously characterizes antibody dynamics and identifies subclinical infections via Bayesian augmentation from detailed cohort data (3,451 individuals with blood draws every 91 days, 143,548 haemagglutination inhibition assay titre measurements). We identify 1,149 infections (95% confidence interval, 1,135-1,163) that were not detected by active surveillance and estimate that 65% of infections are subclinical. After infection, individuals develop a stable set point antibody load after one year that places them within or outside a risk window. Individuals with pre-existing titres of ≤1:40 develop haemorrhagic fever 7.4 (95% confidence interval, 2.5-8.2) times more often than naive individuals compared to 0.0 times for individuals with titres >1:40 (95% confidence interval: 0.0-1.3). Plaque reduction neutralization test titres ≤1:100 were similarly associated with severe disease. Across the population, variability in the size of epidemics results in large-scale temporal changes in infection and disease risk that correlate poorly with age.

  • Case Management of Dengue: Lessons Learned

    Kalayanarooj S, Rothman AL, Srikiatkhachorn A

    J. Infect. Dis. 2017 Mar;215(suppl_2):S79-S88

    PMID: 28403440

    Abstract

    The global burden of dengue and its geographic distribution have increased over the past several decades. The introduction of dengue in new areas has often been accompanied by high case-fatality rates. Drawing on the experience in managing dengue cases at the Queen Sirikit National Institute of Child Health in Bangkok, Thailand, this article provides the authors’ perspectives on key clinical lessons to improve dengue-related outcomes. Parallels between this clinical experience and outcomes reported in randomized controlled trials, results of efforts to disseminate practice recommendations, and suggestions for areas for further research are also discussed.

  • The Influence of Spatial Configuration of Residential Area and Vector Populations on Dengue Incidence Patterns in an Individual-Level Transmission Model

    Kang JY, Aldstadt J

    Int J Environ Res Public Health 2017 Jul;14(7)

    PMID: 28714879

    Abstract

    Dengue is a mosquito-borne infectious disease that is endemic in tropical and subtropical countries. Many individual-level simulation models have been developed to test hypotheses about dengue virus transmission. Often these efforts assume that human host and mosquito vector populations are randomly or uniformly distributed in the environment. Although, the movement of mosquitoes is affected by spatial configuration of buildings and mosquito populations are highly clustered in key buildings, little research has focused on the influence of the local built environment in dengue transmission models. We developed an agent-based model of dengue transmission in a village setting to test the importance of using realistic environments in individual-level models of dengue transmission. The results from one-way ANOVA analysis of simulations indicated that the differences between scenarios in terms of infection rates as well as serotype-specific dominance are statistically significant. Specifically, the infection rates in scenarios of a realistic environment are more variable than those of a synthetic spatial configuration. With respect to dengue serotype-specific cases, we found that a single dengue serotype is more often dominant in realistic environments than in synthetic environments. An agent-based approach allows a fine-scaled analysis of simulated dengue incidence patterns. The results provide a better understanding of the influence of spatial heterogeneity on dengue transmission at a local scale.