Abstract
Two basic strategies have been proposed for using transgenic Aedes aegypti mosquitoes to decrease dengue virus transmission: population reduction and population replacement. Here we model releases of a strain of Ae. aegypti carrying both a gene causing conditional adult female mortality and a gene blocking virus transmission into a wild population to assess whether such releases could reduce the number of competent vectors. We find this “reduce and replace” strategy can decrease the frequency of competent vectors below 50% two years after releases end. Therefore, this combined approach appears preferable to releasing a strain carrying only a female-killing gene, which is likely to merely result in temporary population suppression. However, the fixation of anti-pathogen genes in the population is unlikely. Genetic drift at small population sizes and the spatially heterogeneous nature of the population recovery after releases end prevent complete replacement of the competent vector population. Furthermore, releasing more individuals can be counter-productive in the face of immigration by wild-type mosquitoes, as greater population reduction amplifies the impact wild-type migrants have on the long-term frequency of the anti-pathogen gene. We expect the results presented here to give pause to expectations for driving an anti-pathogen construct to fixation by relying on releasing individuals carrying this two-gene construct. Nevertheless, in some dengue-endemic environments, a spatially heterogeneous decrease in competent vectors may still facilitate decreasing disease incidence.
Highlights
Dengue, an arbovirus vectored primarily by the mosquito Aedes aegypti (Linnaeus), results in approximately 390 million infections each year [1]
Genetic control programs relying on population reduction alone are vulnerable to reinvasion if releases cease by immigrant, wild Ae. aegypti individuals from populations that have not been subject to control efforts [7,8]
We found that releasing transgenic male mosquitoes caused considerable population reduction, fixation of the antipathogen transgene proved elusive even under homogenous releases (Fig. 1B)
Summary
An arbovirus vectored primarily by the mosquito Aedes aegypti (Linnaeus), results in approximately 390 million infections each year [1]. A recently developed female-specific lethal construct allows released individuals to transmit the transgene in the population through their male offspring (e.g., [2,3,4]) Expression of this construct is repressed by rearing mosquito larvae with tetracycline in the water (e.g., [3]), permitting the breeding of large numbers of transgenic mosquitoes for release. The transgene in the strain of [3] that only kills females when they reach the adult stage is attractive because the viable larvae compete with wildtype mosquitoes during the immature stages, in addition to directly reducing the number of adults (e.g., [2,3,5]) This is key because density-dependent population regulation which acts during the larval stage of Ae. aegypti is believed to counteract population suppression efforts (e.g., as may occur in certain sterile-insect methods - [5,6,7]). Genetic control programs relying on population reduction alone are vulnerable to reinvasion if releases cease by immigrant, wild Ae. aegypti individuals from populations that have not been subject to control efforts [7,8]
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