Abstract

Recently there have been significant advances in research on genetic strategies to control populations of disease-vectoring insects. Some of these strategies use the gene drive properties of selfish genetic elements to spread physically linked anti-pathogen genes into local vector populations. Because of the potential of these selfish elements to spread through populations, control approaches based on these strategies must be carefully evaluated to ensure a balance between the desirable spread of the refractoriness-conferring genetic cargo and the avoidance of potentially unwanted outcomes such as spread to non-target populations. There is also a need to develop better estimates of the economics of such releases. We present here an evaluation of two such strategies using a biologically realistic mathematical model that simulates the resident Aedes aegypti mosquito population of Iquitos, Peru. One strategy uses the selfish element Medea, a non-limited element that could permanently spread over a large geographic area; the other strategy relies on Killer-Rescue genetic constructs, and has been predicted to have limited spatial and temporal spread. We simulate various operational approaches for deploying these genetic strategies, and quantify the optimal number of released transgenic mosquitoes needed to achieve definitive spread of Medea-linked genes and/or high frequencies of Killer-Rescue-associated elements. We show that for both strategies the most efficient approach for achieving spread of anti-pathogen genes within three years is generally to release adults of both sexes in multiple releases over time. Even though females in these releases should not transmit disease, there could be public concern over such releases, making the less efficient male-only release more practical. This study provides guidelines for operational approaches to population replacement genetic strategies, as well as illustrates the use of detailed spatial models to assist in safe and efficient implementation of such novel genetic strategies.

Highlights

  • The recent resurgence of dengue as a serious public health issue in many countries around the world [1,2,3] has reinforced the need for efficient and sustainable methods of vector control, since there is currently no practical vaccine or prophylactic drug available against dengue viruses

  • In the current study we focus on the use of genetically modified mosquitoes (GMMs) as population replacement tools [8] where a resident, disease-vectoring population of mosquitoes is replaced by engineered mosquitoes that do not transmit dengue virus

  • If the construct is associated with a fitness cost of cM=0.1 (Figure 1B), a single release of even 20 males per house is not sufficient for the transgenic element to begin spreading in the population

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Summary

Introduction

The recent resurgence of dengue as a serious public health issue in many countries around the world [1,2,3] has reinforced the need for efficient and sustainable methods of vector control, since there is currently no practical vaccine or prophylactic drug available against dengue viruses. In some situations GMM strains could be used as population suppression tools [9,10] This engineering approach is conceptually similar to but potentially more efficient than the classical Sterile Insect Technique (SIT) or classical femalekilling methods [11]. In order to achieve population replacement without repeated GMM releases, these virus resistance-conferring genetic inserts must be linked to a selfish transgenic element that inherently increases its frequency in a population without conferring higher fitness to organisms that contain it [8]. This process is often referred to as genetically engineered gene drive

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