Biology subjects

Espana, G.

Publications and source records attributed to Espana, G..

4 recordsLinked to original sources

bioRxiv2018

DTK-Dengue: A new agent-based model of dengue virus transmission dynamics

Dengue virus (DENV) is a pathogen spread by Aedes mosquitoes that has a considerable impact on global health. Agent-based models can be used to explicitly represent factors that are difficult to measure empirically, by focusing on specific aspects of DENV transmission dynamics that influence spread in a particular location. We present a new agent-based model for DENV dynamics, DTK-Dengue, that can be readily applied to new locations and to a diverse set of goals. It extends the vector-borne disease module in the Institute for Disease Modellings Epidemiological Modeling Disease Transmission Kernel (EMOD-DTK) to model DENV dynamics. There are three key modifications present in DTK-Dengue: 1) modifications to how climatic variables influence vector development for Aedes mosquitoes, 2) updates to adult vector behavior to make them more similar to Aedes, and 3) the inclusion of four DENV serotypes, including their effects on human immunity and symptoms. We demonstrate DTK-Dengues capabilities by fitting the model to four interrelated datasets: total and serotype-specific dengue incidences between January 2007 and December 2008 from San Juan, Puerto Rico; the age distribution of reported dengue cases in Puerto Rico during 2007; and the number of adult female Ae. aegypti trapped in two neighborhoods of San Juan between November 2007 and December 2008. The model replicated broad patterns in the reference data, including a correlation between vector population dynamics and rainfall, appropriate seasonality in the reported incidence, greater circulation of DENV-3 than any other serotype, and an inverse relationship between age and the proportion of cases associated with each age group over 20 years old. This exercise demonstrates the potential for DTK-Dengue to assimilate multiple types of epidemiologic data into a realistic portrayal of DENV transmission dynamics. Due to the open availability of the DTK-Dengue software and the availability of numerous other modules for modeling disease transmission and control from EMOD-DTK, this new model has potential for a diverse range of future applications in a wide variety of settings.

epidemiology↗

bioRxiv2018

Model-based assessment of public health impact and cost-effectiveness of dengue vaccination following screening for prior exposure

The tetravalent dengue vaccine CYD-TDV (Dengvaxia(R)) is the first licensed vaccine against dengue, but recent findings indicate an elevated risk of severe disease among vaccinees without prior dengue virus (DENV) exposure. The World Health Organization currently recommends CYD-TDV only for individuals with serological confirmation of past DENV exposure. Our objective was to evaluate the potential impact and cost-effectiveness of vaccination following serological screening. To do so, we used an agent-based model to simulate DENV transmission with and without vaccination over a 30-year timeframe. Under a range of values for the proportion of vaccinees with prior DENV exposure, we projected the proportion of symptomatic and hospitalized cases averted as a function of the sensitivity and specificity of serological screening. Scenarios about the cost-effectiveness of screening and vaccination were chosen to be representative of Brazil and the Philippines. We found that public health impact depended primarily on the sensitivity of serological screening in high-transmission settings and on a combination of sensitivity and specificity in low-transmission settings. Reducing risk from an individual perspective required high specificity, no less than 0.8. Cost-effectiveness could be achievable from the perspective of a public payer provided that screening sensitivity for prior DENV exposure and the value of a disability-adjusted life-year were both high. Cost-effectiveness was also achievable from an individual perspective, particularly with high screening specificity and low coverage. Whereas the results of this analysis offer general guidelines about CYD-TDV vaccination, decisions in specific contexts would benefit from additional, more context-specific modeling analyses. In conclusion, vaccination with CYD-TDV following serological screening could have a positive impact in certain epidemiological settings, provided that screening is highly specific, at least moderately sensitive, and inexpensive.

epidemiology↗

bioRxiv2018

What lies beneath: a spatial mosaic of Zika virus transmission in the 2015-2016 epidemic in Colombia

Time series data provide a crucial window into infectious disease dynamics, yet their utility is often limited by the spatially aggregated form in which they are presented. When working with time series data, violating the implicit assumption of homogeneous dynamics below the scale of spatial aggregation could bias inferences about underlying processes. We tested this assumption in the context of the 2015-2016 Zika epidemic in Colombia, where time series of weekly case reports were available at national, departmental, and municipal scales. First, we performed a descriptive analysis, which showed that the timing of departmental-level epidemic peaks varied by three months and that departmental-level estimates of the time-varying reproduction number, R(t), showed patterns that were distinct from a national-level estimate. Second, we applied a classification algorithm to six features of proportional cumulative incidence curves, which showed that variability in epidemic duration, the length of the epidemic tail, and consistency with a cumulative normal density curve made the greatest contributions to distinguishing groups. Third, we applied this classification algorithm to data simulated with a stochastic transmission model, which showed that group assignments were consistent with simulated differences in the basic reproduction number, R0. This result, along with associations between spatial drivers of transmission and group assignments based on observed data, suggests that the classification algorithm is capable of detecting differences in temporal patterns that are associated with differences in underlying drivers of incidence patterns. Overall, this diversity of temporal patterns at local scales underscores the value of spatially disaggregated time series data.

epidemiology↗

bioRxiv2016

Statistical and biological uncertainties associated with vaccine efficacy estimates and their implications for dengue vaccine impact projections

Given the limited effectiveness of strategies based solely on vector control to reduce dengue virus (DENV) transmission, it is expected that an effective vaccine could play a pivotal role in reducing the global disease burden of dengue. Of several dengue vaccines under development, Dengvaxia(R) from Sanofi Pasteur recently became the first to become licensed in select countries and to achieve WHO recommendation for use in certain settings, despite the fact that a number of uncertainties about its profile complicate projections of its public health impact. We used a stochastic, agent-based model for DENV transmission to perform simulations of the public health impact of dengue vaccines in light of two key uncertainties: (1) \"statistical uncertainty\" about the numerical value of the vaccines efficacy against disease, and (2) \"biological uncertainty\" about the extent to which its efficacy against disease derives from the amelioration of symptoms, blocking of DENV infection, or some combination thereof. Simulations of a generic dengue vaccine showed that the proportion of disease episodes averted following 20 years of routine vaccination of nine-year olds at 80% coverage was sensitive to both the numerical value of vaccine efficacy and to the extent to which efficacy derives from blocking of DENV infection. Simulations of a vaccine resembling Dengvaxia(R) took into account that vaccine trial results substantially reduced statistical uncertainty but did not address biological uncertainty, resulting in the proportion of disease episodes averted being more sensitive to biological uncertainty than to statistical uncertainty. Taken together, our results indicate limitations associated with the use of symptomatic disease as the primary endpoint of dengue vaccine trials and highlight the importance of considering multiple forms of uncertainty in projections of a vaccines public health impact.

epidemiology↗