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Modeling the dynamics of a non-limited and a self-limited gene drive system in structured Aedes aegypti populations.

ABSTRACT: Recently there have been significant advances in research on genetic strategies to control populations of disease-vectoring insects. Some of these strategies use the gene drive properties of selfish genetic elements to spread physically linked anti-pathogen genes into local vector populations. Because of the potential of these selfish elements to spread through populations, control approaches based on these strategies must be carefully evaluated to ensure a balance between the desirable spread of the refractoriness-conferring genetic cargo and the avoidance of potentially unwanted outcomes such as spread to non-target populations. There is also a need to develop better estimates of the economics of such releases. We present here an evaluation of two such strategies using a biologically realistic mathematical model that simulates the resident Aedes aegypti mosquito population of Iquitos, Peru. One strategy uses the selfish element Medea, a non-limited element that could permanently spread over a large geographic area; the other strategy relies on Killer-Rescue genetic constructs, and has been predicted to have limited spatial and temporal spread. We simulate various operational approaches for deploying these genetic strategies, and quantify the optimal number of released transgenic mosquitoes needed to achieve definitive spread of Medea-linked genes and/or high frequencies of Killer-Rescue-associated elements. We show that for both strategies the most efficient approach for achieving spread of anti-pathogen genes within three years is generally to release adults of both sexes in multiple releases over time. Even though females in these releases should not transmit disease, there could be public concern over such releases, making the less efficient male-only release more practical. This study provides guidelines for operational approaches to population replacement genetic strategies, as well as illustrates the use of detailed spatial models to assist in safe and efficient implementation of such novel genetic strategies.

SUBMITTER: Legros M

PROVIDER: S-EPMC3858347 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Project description:BackgroundThe discovery of CRISPR-based gene editing and its application to homing-based gene drive systems has been greeted with excitement, for its potential to control mosquito-borne diseases on a wide scale, and concern, for the invasiveness and potential irreversibility of a release. Gene drive systems that display threshold-dependent behavior could potentially be used during the trial phase of this technology, or when localized control is otherwise desired, as simple models predict them to spread into partially isolated populations in a confineable manner, and to be reversible through releases of wild-type organisms. Here, we model hypothetical releases of two recently engineered threshold-dependent gene drive systems-reciprocal chromosomal translocations and a form of toxin-antidote-based underdominance known as UDMEL-to explore their ability to be confined and remediated.ResultsWe simulate releases of Aedes aegypti, the mosquito vector of dengue, Zika, and other arboviruses, in Yorkeys Knob, a suburb of Cairns, Australia, where previous biological control interventions have been undertaken on this species. We monitor spread to the neighboring suburb of Trinity Park to assess confinement. Results suggest that translocations could be introduced on a suburban scale, and remediated through releases of non-disease-transmitting male mosquitoes with release sizes on the scale of what has been previously implemented. UDMEL requires fewer releases to introduce, but more releases to remediate, including of females capable of disease transmission. Both systems are expected to be confineable to the release site; however, spillover of translocations into neighboring populations is less likely.ConclusionsOur analysis supports the use of translocations as a threshold-dependent drive system capable of spreading disease-refractory genes into Ae. aegypti populations in a confineable and reversible manner. It also highlights increased release requirements when incorporating life history and population structure into models. As the technology nears implementation, further ecological work will be essential to enhance model predictions in preparation for field trials.

Project description:Dengue fever, the most prevalent global arboviral disease, represents an important public health problem in Indonesia. Control of dengue relies on the control of its main vector, the mosquito Aedes aegypti, yet nothing is known about the population history and genetic structure of this insect in Indonesia. Our aim was to assess the spatio-temporal population genetic structure of Ae. aegypti in Yogyakarta, a densely populated region on Java with common dengue outbreaks.We used multiple marker systems (microsatellites, nuclear and mitochondrial genome-wide single nucleotide polymorphisms generated via Restriction-site Associated DNA sequencing) to analyze 979 Ae. aegypti individuals collected from the Yogyakarta city and the surrounding hamlets during the wet season in 2011 and the following dry season in 2012. We employed individual- and group-based approaches for inferring genetic structure.We found that Ae. aegypti in Yogyakarta has spatially structured and seasonally stable populations. The spatial structuring was significant for the nuclear and mitochondrial markers, while the temporal structuring was non-significant. Nuclear markers identified three main genetic clusters, showing that hamlets have greater genetic isolation from each other and from the inner city sites. However, one hamlet experienced unrestricted mosquito interbreeding with the inner city, forming a single genetic cluster. Genetic distance was poorly correlated with the spatial distance among mosquito samples, suggesting stronger influence of human-assisted gene flow than active mosquito movement on spatial genetic structure. A star-shaped mitochondrial haplotype network and a significant R(2) test statistic (R(2)?=?0.0187, P?=?0.001) support the hypothesis that Ae. aegypti in Yogyakarta originated from a small or homogeneous source and has undergone a relatively recent demographic expansion.We report the first insights into the spatio-temporal genetic structure and the underlying processes in the dengue fever mosquito from Yogyakarta, Indonesia. Our results provide valuable information on the effectiveness of local control measures as well as guidelines for the implementation of novel biocontrol strategies such as release of Wolbachia-infected mosquitoes.

Project description:BackgroundThe global incidences of dengue virus have increased the interest in studying and understanding the mosquito population dynamics. It is predominantly spread by Aedes aegypti in the tropical and sub-tropical countries in the world. Understanding these dynamics is important for public health in countries where climatic and environmental conditions are favorable for the propagation of these diseases. For this reason, a new model has been proposed to investigate the population dynamics of mosquitoes in a city.MethodsThe present paper discusses the numerical modeling of population dynamics of Ae. aegypti mosquitoes in an urban neighborhood of a city using the finite volume method. The model describes how populations spread through the city assisted by the wind. This model allows incorporating external factors (wind and chemical insecticides) and topography data (streets, building blocks, parks, forests and beach). The proposed model has been successfully tested in examples involving two Brazilian cities (City center, Juiz de Fora and Copacabana Beach, Rio de Janeiro).ResultsInvasion phenomena of Ae. aegypti mosquitoes have been observed in each of the simulations. It was observed that, inside the blocks, the growth of the population for both winged and aquatic phase causes an infestation of Ae. aegypti in a short time. Within the blocks the mosquito population was concentrated and diffused slowly. In the streets, there was a long-distance spread, which was influenced by wind and diffusion with a low concentration of mosquito population. The model was also tested taking into account chemical insecticides spread in two different configurations. It has been observed that the insecticides have a significant effect on the mosquito population for both winged and aquatic phases when the chemical insecticides spread more uniformly along all the streets in a neighborhood of a city.ConclusionsThe presented methodology can be employed to evaluate and to understand the epidemic risks in a specific region of the city. Moreover the model allows an increase in efficiency of the existing mosquito population control techniques and to theoretically test new methods before involving the human population.

Project description:BackgroundTemperature and humidity strongly affect the physiology, longevity, fecundity and dispersal behavior of Aedes aegypti, vector of dengue fever. Contrastingly, the statistical associations measured between time series of mosquito abundance and meteorological variables are often weak and contradictory. Here, we investigated the significance of these relationships at different time scales.Methods and findingsA time series of the adult mosquito abundance from a medium-sized city in Brazil, lasting 109 weeks was analyzed. Meteorological variables included temperature, precipitation, wind velocity and humidity. As analytical tools, generalized linear models (GLM) with time lags and interaction terms were used to identify average effects while the wavelet analysis was complementarily used to identify transient associations. The fitted GLM showed that mosquito abundance is significantly affected by the interaction between lagged temperature and humidity, and also by the mosquito abundance a week earlier. Extreme meteorological variables were the best predictors, and the mosquito population tended to increase at values above [Formula: see text] and 54% humidity. The wavelet analysis identified non-stationary local effects of these meteorological variables on abundance throughout the study period, with peaks in the spring-summer period. The wavelet detected weak but significant effects for precipitation and wind velocity.ConclusionOur results support the presence of transient relationships between meteorological variables and mosquito abundance. Such transient association may be explained by the ability of Ae. aegypti to buffer part of its response to climate, for example, by choosing sites with proper microclimate. We also observed enough coupling between the abundance and meteorological variables to develop a model with good predictive power. Extreme values of meteorological variables with time lags, interaction terms and previous mosquito abundance are strong predictors and should be considered when understanding the climate effect on mosquito abundance and population growth.

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Modeling the dynamics of a non-limited and a self-limited gene drive system in structured Aedes aegypti populations.

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