Biology subjects

Perkins, A.

Publications and source records attributed to Perkins, A..

9 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

Inter-annual variation in seasonal dengue epidemics driven bymultiple interacting factors in Guangzhou, China

Vector-borne diseases display wide inter-annual variation in seasonal epidemic size due to their complex dependence on temporally variable environmental conditions and other factors. In 2014, Guangzhou, China experienced its worst dengue epidemic on record, with incidence exceeding the historical average by two orders of magnitude. To disentangle contributions from multiple factors to inter-annual variation in epidemic size, we fitted a semi-mechanistic model to time series data from 2005-2015 and performed a series of factorial simulation experiments in which seasonal epidemics were simulated under all combinations of year-specific patterns of four time-varying factors: imported cases, mosquito density, temperature, and residual variation in local conditions not explicitly represented in the model. Our results indicate that while epidemics in most years were limited by unfavorable conditions with respect to one or more factors, the epidemic in 2014 was made possible by the combination of favorable conditions for all factors considered in our analysis.

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↗

bioRxiv2017

The Basic Reproductive Number for Disease Systems with Multiple Coupled Heterogeneities

In mathematical epidemiology, a well-known formula describes the impact of heterogeneity on the basic reproductive number, R0, for situations in which transmission is separable and for which there is one source of variation in susceptibility and one source of variation in infectiousness. This formula is written in terms of the magnitudes of the heterogeneities, as quantified by their coefficients of variation, and the correlation between them. A natural question to ask is whether analogous results apply when there are multiple sources of variation in susceptibility and/or infectiousness. In this paper we demonstrate that with three or more coupled heterogeneities, R0 under separable transmission depends on details of the distribution of the heterogeneities in a way that is not seen in the well-known simpler situation. We provide explicit formulae for the cases of multivariate normal and multivariate log-normal distributions, showing that R0 can again be expressed in terms of the magnitudes of the heterogeneities and the pairwise correlations between them. The formulae, however, differ between the two multivariate distributions, demonstrating that no formula of this type applies generally when there are three or more coupled heterogeneities. We see that the results of the formulae are approximately equal when heterogeneities are relatively small and show that an earlier result in the literature (Koella, 1991) should be viewed in this light. We provide numerical illustrations of our results and discuss a setting in which coupled heterogeneities are likely to have a major impact on the value of R0. We also describe a rather surprising result: in a system with three heterogeneities, R0 can exhibit non-monotonic behavior with increasing levels of heterogeneity, in marked contrast to the familiar two heterogeneity setting in which R0 either increases or decreases with increasing heterogeneity.

epidemiology↗

bioRxiv2017

The population genetics of spatial sorting

In most systems, dispersal occurs despite clear fitness costs to dispersing individuals. Theory posits that spatial heterogeneity in habitat quality pushes dispersal rates to evolve towards zero, while temporal heterogeneity in habitat quality favours non-zero dispersal rates. One aspect of dispersal evolution that has received a great deal of recent attention is a process known as spatial sorting, which has been referred to as a \"shy younger sibling\" of natural selection. More precisely, spatial sorting is the process whereby variation in dispersal ability is sorted along density clines and will, in nature, often be a transient phenomenon. Despite this transience, spatial sorting is likely a general mechanism behind non-zero dispersal in spatiotemporally varying environments. While generally transient, spatial sorting is persistent on invasion fronts, where its effect cannot be ignored, causing rapid evolution of traits related to dispersal. Spatial sorting is described in several elegant models, yet these models require a high level of mathematical sophistication and are not accessible to most evolutionary biologists or their students. Here, we frame spatial sorting in terms of the classic haploid and diploid models of natural selection. We show that, on an invasion front, spatial sorting can be conceptualized precisely as selection operating through space rather than (as with natural selection) time, and that genotypes can be viewed as having both spatial and temporal aspects of fitness. The resultant model is strikingly similar to classic models of natural selection. This similarity renders the model easy to understand (and to teach), but also suggests that many established theoretical results around natural selection could apply equally to spatial sorting.

evolutionary biology↗

bioRxiv2017

Preliminary results of models to predict areas in the Americas with increased likelihood of Zika virus transmission in 2017.

Numerous Zika virus vaccines are being developed. However, identifying sites to evaluate the efficacy of a Zika virus vaccine is challenging due to the general decrease in Zika virus activity. We compare results from three different modeling approaches to estimate areas that may have increased relative risk of Zika virus transmission during 2017. The analysis focused on eight priority countries (i.e., Brazil, Colombia, Costa Rica, Dominican Republic, Ecuador, Mexico, Panama, and Peru). The models projected low incidence rates during 2017 for all locations in the priority countries but identified several subnational areas that may have increased relative risk of Zika virus transmission in 2017. Given the projected low incidence of disease, the total number of participants, number of study sites, or duration of study follow-up may need to be increased to meet the efficacy study endpoints.

epidemiology↗

bioRxiv2017

Model-based analysis of experimental hut data elucidates multifaceted effects of a volatile chemical on Aedes aegypti mosquitoes

BackgroundInsecticides used against Aedes aegypti and other disease vectors can elicit a multitude of dose-dependent effects on behavioral and bionomic traits. Estimating the potential epidemiological impact of a product requires thorough understanding of these effects and their interplay at different dosages. Volatile spatial repellent (SR) products come with an additional layer of complexity due to the potential for movement of affected mosquitoes or volatile particles of the product beyond the treated house. Here, we propose a statistical inference framework for estimating these nuanced effects of volatile SRs.\n\nMethodsWe fitted a continuous-time Markov chain model in a Bayesian framework to mark-release-recapture (MRR) data from an experimental hut study conducted in Iquitos, Peru. We estimated the effects of two dosages of transfluthrin on Ae. aegypti behaviors associated with human-vector contact: repellency, exiting, and knockdown in the treated space and in \"downstream\" adjacent huts. We validated the framework using simulated data.\n\nResultsThe odds of a female Ae. aegypti being repelled from a treated hut (HT) increased at both dosages (low dosage: odds = 1.64, 95% highest density interval (HDI) = 1.30-2.09; high dosage: odds = 1.35, HDI = 1.04-1.67). The relative risk of exiting from the treated hut was reduced (low: RR = 0.70, HDI = 0.62-1.09; high: RR = 0.70, HDI = 0.40-1.06), with this effect carrying over to untreated spaces as far as two huts away from the treated hut (H2) (low: RR = 0.79, HDI = 0.59-1.01; high: RR = 0.66, HDI = 0.50-0.87). Knockdown rates were increased in both treated and downstream huts, particularly under high dosage (HT: RR = 8.37, HDI = 2.11-17.35; H1: RR = 1.39, HDI = 0.52-2.69; H2: RR = 2.22, HDI = 0.96-3.86).\n\nConclusionsOur statistical inference framework is effective at elucidating multiple effects of volatile chemicals used in SR products, as well as their downstream effects. This framework provides a powerful tool for early selection of candidate SR product formulations worth advancing to costlier epidemiological trials, which are ultimately necessary for proof of concept of public health value and subsequent formal endorsement by health authorities.

ecology↗

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↗