Abstract

BackgroundThe use of gene drive systems to manipulate populations of malaria vectors is currently being investigated as a method of malaria control. One potential system uses driving endonuclease genes (DEGs) to spread genes that impose a genetic load. Previously, models have shown that the introduction of DEG-bearing mosquitoes could suppress or even extinguish vector populations in spatially-heterogeneous environments which were constant over time. In this study, a stochastic spatially-explicit model of mosquito ecology is combined with a rainfall model which enables the generation of a variety of daily precipitation patterns. The model is then used to investigate how releases of a DEG that cause a bias in population sex ratios towards males are affected by seasonal or random rainfall patterns. The parameters of the rainfall model are then fitted using data from Bamako, Mali, and Mbita, Kenya, to evaluate release strategies in similar climatic conditions.ResultsIn landscapes with abundant resources and large mosquito populations the spread of a DEG is reliable, irrespective of variability in rainfall. This study thus focuses mainly on landscapes with low density mosquito populations where the spread of a DEG may be sensitive to variation in rainfall. It is found that an introduced DEG will spread into its target population more reliably in wet conditions, yet an established DEG will have more impact in dry conditions. In strongly seasonal environments, it is thus preferable to release DEGs at the onset of a wet season to maximize their spread before the following dry season. If the variability in rainfall has a substantial random component, there is a net increase in the probability that a DEG release will lead to population extinction, due to the increased impact of a DEG which manages to establish in these conditions. For Bamako, where annual rainfall patterns are characterized by a long dry season, it is optimal to release a DEG at the start of the wet season, where the population is growing fastest. By contrast release timing is of lower importance for the less seasonal Mbita.ConclusionThis analysis suggests that DEG based methods of malaria vector control can be effective in a wide range of climates. In environments with substantial temporal variation in rainfall, careful timing of releases which accounts for the temporal variation in population density can substantially improve the probability of mosquito suppression or extinction.

Highlights

  • The use of gene drive systems to manipulate populations of malaria vectors is currently being investigated as a method of malaria control

  • In a sparser landscape with only 4 houses k­ m−2, fixation occurred in half the simulations, while the driving endonuclease genes (DEGs) became extinct with no lasting consequences in the remaining half

  • In 80% of the cases where the DEG became fixed, the population was driven to extinction; in the remaining 20% of these cases the population continued to persist through the course of the simulation the population size was greatly reduced from the pre-DEG level

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Summary

Introduction

The use of gene drive systems to manipulate populations of malaria vectors is currently being investigated as a method of malaria control. Genetic manipulation using driving endonuclease genes (DEGs) offers the potential of suppressing vector populations [7]. For use in vector control, a DEG could be inserted into a functional mosquito gene in order to induce a population-wide knockout of that gene [9, 10]. A DEG could be inserted onto the Y-chromosome so that in heterozygote males it disrupts the X-chromosome and biases the sex-ratio towards male offspring (“Y-drive”). Both approaches aim to either suppress or eliminate the target vector population

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