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Assessing the feasibility of controlling Aedes aegypti with transgenic methods: a model-based evaluation.

ABSTRACT: Suppression of dengue and malaria through releases of genetically engineered mosquitoes might soon become feasible. Aedes aegypti mosquitoes carrying a conditionally lethal transgene have recently been used to suppress local vector populations in small-scale field releases. Prior to releases of transgenic insects on a wider scale, however, most regulatory authorities will require additional evidence that suppression will be effective in natural heterogeneous habitats. We use a spatially explicit stochastic model of an Ae. aegypti population in Iquitos, Peru, along with an uncertainty analysis of its predictions, to quantitatively assess the outcome of varied operational approaches for releases of transgenic strains with conditional death of females. We show that population elimination might be an unrealistic objective in heterogeneous populations. We demonstrate that substantial suppression can nonetheless be achieved if releases are deployed in a uniform spatial pattern using strains combining multiple lethal elements, illustrating the importance of detailed spatial models for guiding genetic mosquito control strategies.

SUBMITTER: Legros M

PROVIDER: S-EPMC3528761 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Assessing the feasibility of controlling Aedes aegypti with transgenic methods: a model-based evaluation.

Legros Mathieu M Xu Chonggang C Okamoto Kenichi K Scott Thomas W TW Morrison Amy C AC Lloyd Alun L AL Gould Fred F

PloS one 20121221 12

Suppression of dengue and malaria through releases of genetically engineered mosquitoes might soon become feasible. Aedes aegypti mosquitoes carrying a conditionally lethal transgene have recently been used to suppress local vector populations in small-scale field releases. Prior to releases of transgenic insects on a wider scale, however, most regulatory authorities will require additional evidence that suppression will be effective in natural heterogeneous habitats. We use a spatially explicit ...[more]

PMID: 23284949

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Project description:The mosquito immune system is involved in pathogen-elicited defense responses. The NF-?B factors REL1 and REL2 are downstream transcription activators of Toll and IMD immune pathways, respectively. We have used genome-wide microarray analyses to characterize fat-body-specific gene transcript repertoires activated by either REL1 or REL2 in two transgenic strains of the mosquito Aedes aegypti. Vitellogenin gene promoter was used in each transgenic strain to ectopically express either REL1 (REL1+) or REL2 (REL2+) in a sex, tissue, and stage specific manner. There was a significant change in the transcript abundance of 297 (79 up- and 218 down-regulated) and 299 (123 up- and 176 down-regulated) genes in fat bodies of REL1+ and REL2+, respectively. Over half of the induced genes had predicted functions in immunity, and a large group of these was co-regulated by REL1 and REL2. By generating a hybrid transgenic strain, which ectopically expresses both REL1 and REL2, we have shown a synergistic action of these NF-?B factors in activating immune genes. The REL1+ immune transcriptome showed a significant overlap with that of cactus (RNAi)-depleted mosquitoes (50%). In contrast, the REL2+ -regulated transcriptome differed from the relatively small group of gene transcripts regulated by RNAi depletion of a putative inhibitor of the IMD pathway, caspar (35 up- and 140 down-regulated), suggesting that caspar contributes to regulation of a subset of IMD-pathway controlled genes. Infections of the wild type Ae. aegypti with Plasmodium gallinaceum elicited the transcription of a distinct subset of immune genes (76 up- and 25 down-regulated) relative to that observed in REL1+ and REL2+ mosquitoes. Considerable overlap was observed between the fat body transcriptome of Plasmodium-infected mosquitoes and that of mosquitoes with transiently depleted PIAS, an inhibitor of the JAK-STAT pathway. PIAS gene silencing reduced Plasmodium proliferation in Ae. aegypti, indicating the involvement of the JAK-STAT pathway in anti-Plasmodium defense in this infection model.

Project description:BackgroundAedes aegypti is one of the most important mosquito vectors of human disease. The development of spatial models for Ae. aegypti provides a promising start toward model-guided vector control and risk assessment, but this will only be possible if models make reliable predictions. The reliability of model predictions is affected by specific sources of uncertainty in the model.Methodology/principal findingsThis study quantifies uncertainties in the predicted mosquito population dynamics at the community level (a cluster of 612 houses) and the individual-house level based on Skeeter Buster, a spatial model of Ae. aegypti, for the city of Iquitos, Peru. The study considers two types of uncertainty: 1) uncertainty in the estimates of 67 parameters that describe mosquito biology and life history, and 2) uncertainty due to environmental and demographic stochasticity. Our results show that for pupal density and for female adult density at the community level, respectively, the 95% prediction confidence interval ranges from 1000 to 3000 and from 700 to 5,000 individuals. The two parameters contributing most to the uncertainties in predicted population densities at both individual-house and community levels are the female adult survival rate and a coefficient determining weight loss due to energy used in metabolism at the larval stage (i.e. metabolic weight loss). Compared to parametric uncertainty, stochastic uncertainty is relatively low for population density predictions at the community level (less than 5% of the overall uncertainty) but is substantially higher for predictions at the individual-house level (larger than 40% of the overall uncertainty). Uncertainty in mosquito spatial dispersal has little effect on population density predictions at the community level but is important for the prediction of spatial clustering at the individual-house level.Conclusion/significanceThis is the first systematic uncertainty analysis of a detailed Ae. aegypti population dynamics model and provides an approach for identifying those parameters for which more accurate estimates would improve model predictions.

Project description:BackgroundSkeeter Buster is a stochastic, spatially explicit simulation model of Aedes aegypti populations, designed to predict the outcome of vector population control methods. In this study, we apply the model to two specific locations, the cities of Iquitos, Peru, and Buenos Aires, Argentina. These two sites differ in the amount of field data that is available for location-specific customization. By comparing output from Skeeter Buster to field observations in these two cases we evaluate population dynamics predictions by Skeeter Buster with varying degrees of customization.Methodology/principal findingsSkeeter Buster was customized to the Iquitos location by simulating the layout of houses and the associated distribution of water-holding containers, based on extensive surveys of Ae. aegypti populations and larval habitats that have been conducted in Iquitos for over 10 years. The model is calibrated by adjusting the food input into various types of containers to match their observed pupal productivity in the field. We contrast the output of this customized model to the data collected from the natural population, comparing pupal numbers and spatial distribution of pupae in the population. Our results show that Skeeter Buster replicates specific population dynamics and spatial structure of Ae. aegypti in Iquitos. We then show how Skeeter Buster can be customized for Buenos Aires, where we only had Ae. aegypti abundance data that was averaged across all locations. In the Argentina case Skeeter Buster provides a satisfactory simulation of temporal population dynamics across seasons.ConclusionsThis model can provide a faithful description of Ae. aegypti populations, through a process of location-specific customization that is contingent on the amount of data available from field collections. We discuss limitations presented by some specific components of the model such as the description of food dynamics and challenges that these limitations bring to model evaluation.

Project description:The mosquito Aedes aegypti is the main vector of arboviroses and current approaches to control this vector are not sufficiently effective. Adult traps, such as the BG-Sentinel (BGS), have been successfully used for mosquito surveillance and can also suppress vector populations. A new "passive" trap for gravid Ae. aegypti (Gravid Aedes Trap-GAT) has been shown efficient for Aedes collection and suppress Ae. albopictus populations using mass trapping techniques. Here the GAT was evaluated for the first time as a new tool to control Ae. aegypti in semi-field conditions using simulated outdoor environments (SOE). Two identical large screened chambers inside of a SOE containing different numbers and sizes of artificial breeding sites were used to assess the trapping efficiency of the GAT. One hundred mosquitoes were released into the chambers, and recapture rates evaluated after 48h. The parity status of the captured mosquitoes was also recorded. The number of eggs laid, and breeding productivity were also monitored when using different numbers and sizes of breeding sites. The BGS trap was used here as a control (gold standard) trap to compare capture rates to those of the GAT. The GAT recaptured between 50-65% of the mosquitoes independent of the number and sizes of the breeding sites in the SOEs, whereas the BGS recaptured 60-82% of the females. Both traps showed similar results regarding to the parity status of recaptured mosquitoes. Our results confirmed the effectiveness of GAT for the capture of adult female Ae. aegypti in simulated field environments. The BGS trap recaptured gravid Ae. aegypti before egg-laying in different sizes and number of breading sites, whereas the oviposition activity occurred prior to recapture mosquitoes in the GAT. Based on the results, we believe that GAT is a promising candidate for mass-trapping intervention in urban settings, but a source reduction intervention should be made prior trap deployment. Therefore, we suggest future field studies to confirm the use of GAT as a complementary tool in vector control activities.

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Assessing the feasibility of controlling Aedes aegypti with transgenic methods: a model-based evaluation.

Publications

Assessing the feasibility of controlling Aedes aegypti with transgenic methods: a model-based evaluation.

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