Genetic control of Aedes aegypti: data-driven modelling to assess the effect of releasing different life stages and the potential for long-term suppression

Background Control of the world’s most important vector-borne viral disease, dengue, is a high priority. A lack of vaccines or effective vector control methods means that novel solutions to disease control are essential. The release of male insects carrying a dominant lethal (RIDL) is one such approach that could be employed to control Aedes aegypti. To maximise the potential of RIDL control, optimum release strategies for transgenic mosquitoes are needed. The use of field data to parameterise models allowing comparisons of the release of different life-stages is presented together with recommendations for effective long-term suppression of a wild Ae. aegypti population. Methods A compartmental, deterministic model was designed and fitted to data from large-scale pupal mark release recapture (MRR) field experiments to determine the dynamics of a pupal release. Pulsed releases of adults, pupae or a combination of the two were simulated. The relative ability of different release methods to suppress a simulated wild population was examined and methods to maintain long-term suppression of a population explored. Results The pupal model produced a good fit to field data from pupal MRR experiments. Simulations using this model indicated that adult-only releases outperform pupal-only or combined releases when releases are frequent. When releases were less frequent pupal-only or combined releases were a more effective method of distributing the insects. The rate at which pupae eclose and emerge from release devices had a large influence on the relative efficacy of pupal releases. The combined release approach allows long-term suppression to be maintained with smaller low-frequency releases than adult- or pupal-only release methods. Conclusions Maximising the public health benefits of RIDL-based vector control will involve optimising all stages of the control programme. The release strategy can profoundly affect the outcome of a control effort. Adult-only, pupal-only and combined releases all have relative advantages in certain situations. This study successfully integrates field data with mathematical models to provide insight into which release strategies are best suited to different scenarios. Recommendations on effective approaches to achieve long-term suppression of a wild population using combined releases of adults and pupae are provided

Open field release of genetically engineered sterile male Aedes aegypti in Malaysia.

BackgroundDengue is the most important mosquito-borne viral disease. In the absence of specific drugs or vaccines, control focuses on suppressing the principal mosquito vector, Aedes aegypti, yet current methods have not proven adequate to control the disease. New methods are therefore urgently needed, for example genetics-based sterile-male-release methods. However, this requires that lab-reared, modified mosquitoes be able to survive and disperse adequately in the field.Methodology/principal findingsAdult male mosquitoes were released into an uninhabited forested area of Pahang, Malaysia. Their survival and dispersal was assessed by use of a network of traps. Two strains were used, an engineered 'genetically sterile' (OX513A) and a wild-type laboratory strain, to give both absolute and relative data about the performance of the modified mosquitoes. The two strains had similar maximum dispersal distances (220 m), but mean distance travelled of the OX513A strain was lower (52 vs. 100 m). Life expectancy was similar (2.0 vs. 2.2 days). Recapture rates were high for both strains, possibly because of the uninhabited nature of the site.Conclusions/significanceAfter extensive contained studies and regulatory scrutiny, a field release of engineered mosquitoes was safely and successfully conducted in Malaysia. The engineered strain showed similar field longevity to an unmodified counterpart, though in this setting dispersal was reduced relative to the unmodified strain. These data are encouraging for the future testing and implementation of genetic control strategies and will help guide future field use of this and other engineered strains

Study and monitored areas in Bentong, Pahang, Malaysia.

<p>(a) The release was conducted in an uninhabited area comprising a jungle area (government land), a cleared area and a young rubber plantation where a network of 45 adult traps (BG-Sentinel) and 44 ovitraps were set. The closest inhabited areas were monitored with 35 ovitraps only, (release point: red star; uninhabited study area: green area; inhabited monitored area: blue area) (Credits for small scale map: © 2012 Google; © 2012 Tele Atlas; © 2012 TerraMetrics; Credits for large scale map: © 2012 Google; © 2012 GeoEye; © 2012 Cnes/Spot Image; © 2012 Mapit). (b) The BG-Sentinel traps were principally set in the cleared area on the small terraces surrounding the release point and uphill on a small path through the forest until around 100 m from the release point. Further traps were placed downhill in the rubber plantation along the road leading to the closest inhabited area. (Release point: red star; BG-Sentinel™ traps: circles; Altitude: contour lines (separated by 10 m)).</p