Systematic identification of plausible pathways to potential harm via problem formulation for investigational releases of a population suppression gene drive to control the human malaria vector Anopheles gambiae in West Africa.

Background: Population suppression gene drive has been proposed as a strategy for malaria vector control. A CRISPR-Cas9-based transgene homing at the doublesex locus (dsxF) has recently been shown to increase rapidly in frequency in, and suppress, caged laboratory populations of the malaria mosquito vector Anopheles gambiae. Here, problem formulation, an initial step in environmental risk assessment (ERA), was performed for simulated field releases of the dsxF transgene in West Africa.

Detecting the population dynamics of an autosomal sex ratio distorter transgene in malaria vector mosquitoes.

The development of genetically modified (GM) mosquitoes and their subsequent field release offers innovative and cost-effective approaches to reduce mosquito-borne diseases, such as malaria. A sex-distorting autosomal transgene has been developed recently in G3 mosquitoes, a laboratory strain of the malaria vector s.l.

Anopheles gambiae (s.l.) is found where few are looking: assessing mosquito diversity and density outside inhabited areas using diverse sampling methods.

Background: One of the promising current approaches to curb malaria lies in genetic vector control, the implementation of which will require an improved understanding of the movement of genetic constructs among mosquito populations. To predict potential gene flow from one area to another, it is important to begin to understand mosquito dynamics outside of the commonly-sampled village areas, and thus how genes may move between villages. This study assessed the presence and relative abundance of mosquitoes in a 6-km corridor between two villages in western Burkina Faso.

Modelling the suppression of a malaria vector using a CRISPR-Cas9 gene drive to reduce female fertility.

Background: Gene drives based on CRISPR-Cas9 technology are increasingly being considered as tools for reducing the capacity of mosquito populations to transmit malaria, and one of the most promising options is driving endonuclease genes that reduce the fertility of female mosquitoes. In particular, there is much interest in constructs that target the conserved mosquito doublesex (dsx) gene such that the emergence of functional drive-resistant alleles is unlikely. Proof of principle that these constructs can lead to substantial population suppression has been obtained in population cages, and they are being evaluated for use in sub-Saharan Africa.

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

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 km 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.

Large-cage assessment of a transgenic sex-ratio distortion strain on populations of an African malaria vector.

Background: Novel transgenic mosquito control methods require progressively more realistic evaluation. The goal of this study was to determine the effect of a transgene that causes a male-bias sex ratio on Anopheles gambiae target populations in large insectary cages.

Methods: Life history characteristics of Anopheles gambiae wild type and Ag(PMB)1 (aka 124L-2) transgenic mosquitoes, whose progeny are 95% male, were measured in order to parameterize predictive population models.

Modelling the persistence of mosquito vectors of malaria in Burkina Faso.

Background: Populations of the Anopheles gambiae complex are found during the rainy season throughout West Africa, even in arid areas with long dry seasons during which mosquitoes appear to be absent. Several hypotheses have been proposed to explain this apparent paradox, including aestivation, dispersal between neighbouring settlements, and long distance migration using high-altitude wind currents.

Methods: An individual-based, spatially explicit model of mosquito populations was developed for a region of West Africa centred on, and including all of, Burkina Faso.

The dynamics of disease in a metapopulation: The role of dispersal range.

The establishment and spread of a disease within a metapopulation is influenced both by dynamics within each population and by the host and pathogen spatial processes through which they are connected. We develop a spatially explicit metapopulation model to investigate how the form of host and disease dispersal jointly influence the probability of disease establishment and invasion. We show that diseases are more likely to establish if both the host and the disease tend to disperse locally, since the former leads to the spatial aggregation of host populations in the environment while the latter facilitates the pathogen's exploitation of this spatial pattern.