Modelling the potential of genetic control of malaria mosquitoes at national scale

Abstract

Background The persistence of malaria in large parts of sub-Saharan Africa has motivated the development of novel tools to complement existing control programmes, including gene-drive technologies to modify mosquito vector populations. Here, we use a stochastic simulation model to explore the potential of using a driving-Y chromosome to suppress vector populations in a 10 6 km 2 area of West Africa including all of Burkina Faso. Results The consequence of driving-Y introductions is predicted to vary across the landscape, causing elimination of the target species in some regions and suppression in others. We explore how this variation is determined by environmental conditions, mosquito behaviour, and the properties of the gene-drive. Seasonality is particularly important, and we find population elimination is more likely in regions with mild dry seasons whereas suppression is more likely in regions with strong seasonality. Conclusions Despite the spatial heterogeneity, we suggest that repeated introductions of modified mosquitoes over a few years into a small fraction of human settlements may be sufficient to substantially reduce the overall number of mosquitoes across the entire geographic area. Electronic supplementary material The online version of this article (10.1186/s12915-019-0645-5) contains supplementary material, which is available to authorized users.

Using problem formulation for fit‐for‐purpose pre‐market environmental risk assessments of regulated stressors

“…Any genetic element that is inherited at a greater frequency than predicted through Mendelian genetics can be referred to as a ‘gene drive’. Gene drives positively bias their own inheritance and thus spread rapidly through populations, even if they incur a fitness cost (North et al., ). First reported in the 1950s, natural gene drives have been well‐characterised (Hammond and Galizi, ).…”

“…These type of gene drives are also referred to as temporally limited drives. Examples are daisy-chain gene drives (Noble et al, 2019) and killer-rescue drives (Gould et al, 2008).…”

Suppression gene drive in continuous space can result in unstable persistence of both drive and wild-type alleles

“…The third suppression system is a Driving Y chromosome, which involves inserting the drive on the Y chromosome. In the "X-shredder" variant we consider here, the drive cleaves sites located on the X chromosome during meiosis 22,24 . With a high cleavage rate, most X chromosomes in the germline of a drive-carrying male are destroyed, resulting in most viable sperm containing the Y chromosome.…”

“…Panmictic population models have been useful in identifying optimal gene drive parameters and studying the effects of phenomena such as the evolution of resistance [16][17][18][19] . Yet it has also become clear that to accurately understand the full range of outcomes of a gene drive release, spatial factors must be explicitly considered [20][21][22][23][24][25] . Panmictic models typically predict, for instance, that a suppression drive will either successfully eliminate a population or be quickly lost.…”

“…Spatial structure can also lead to coexistence of drive and wild-type alleles where panmictic models would predict that one would always outcompete the other quickly. For example, in a mosquito-specific simulation of a malaria-endemic nation represented by a network of linked panmictic populations, "metapopulation dynamics" were frequently observed, wherein a drive invasion resulted in local population elimination, which was then followed by recolonization by wild-type individuals 24 . Another study showed that an equilibrium can exist between empty space, regions with only wild-type alleles, and regions also containing drive alleles 26 .…”