Controlling vector-borne diseases by releasing modified mosquitoes

Abstract

Aedes mosquito-transmitted diseases, such as dengue, Zika and chikungunya, are becoming major global health emergencies while old threats, such as yellow fever, are re-emerging. Traditional control methods, which have focused on reducing mosquito populations through the application of insecticides or preventing breeding through removal of larval habitat, are largely ineffective, as evidenced by the increasing global disease burden. Here, we review novel mosquito population reduction and population modification approaches with a focus on control methods based on the release of mosquitoes, including the release of Wolbachia-infected mosquitoes and strategies to genetically modify the vector, that are currently under development and have the potential to contribute to a reversal of the current alarming disease trends.

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Fig. 1: The global distribution and burden of dengue.
Fig. 2: Modification of vectors for population reduction.
Fig. 3: Using Wolbachia to reduce or modify populations.
Fig. 4: Gene drive approaches to modify or reduce populations.

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Acknowledgements

The authors are grateful to M. Woolfit for reviewing the manuscript and acknowledge funding from The Foundation for the National Institutes of Health through the Vector-Based Transmission of Control: Discovery Research (VCTR) program of the Grand Challenges in Global Health initiative of the Bill & Melinda Gates Foundation and The Wellcome Trust Award No. 102591.

Reviewer information

Nature Reviews Microbiology thanks G. Hamer, P. McCall and the other anonymous reviewer(s) for their contribution to the peer review of this work.

Author information

H.A.F. researched data for the article. S.L.O’N. and H.A.F. made substantial contributions to discussions of the content, wrote the article and reviewed and/or edited the manuscript before submission.

Correspondence to Scott L. O’Neill.

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H.A.F. and S.L.O’N. work for the World Mosquito Program.

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Glossary

Aedes aegypti

The primary mosquito vector of epidemic transmission for viruses, such as dengue, zika and chikungunya. A. aegypti is prevalent primarily in tropical and subtropical regions of the world and is particularly adapted to urban habitats.

Sterile insect technique

(SIT). The radiation or chemical treatment of male mosquitoes, which renders them sterile. When they are released in the field and they mate with wild-type females, they cannot produce offspring.

Incompatible insect technique

(ITT). The release of Wolbachia-infected males, which, when mated with wild-type females that contain no Wolbachia or a different, incompatible strain of Wolbachia, produce no offspring owing to cytoplasmic incompatibility.

Wolbachia pipientis

A naturally occurring bacterial endosymbiont that is estimated to be present in 40–60% of all insect species. Commonly referred to as just Wolbachia.

CRISPR–Cas9

A genome-editing tool that was developed from adaptive immune systems found in bacteria and archaea. The system is composed of a nuclease, Cas9 and a guide RNA that targets the nuclease to a specific DNA sequence for cleavage.

Cytoplasmic incompatibility

(CI). When Wolbachia-infected male mosquitoes mate with uninfected females, the resulting progeny die during early embryogenesis. If the female is also infected with the same Wolbachia strain, that infection can rescue the embryonic lethality, resulting in viable progeny.

Vector competence

A measure of the ability of arthropod vectors to acquire and transmit viruses in their saliva.

Ovitraps

Traps designed for the collection of mosquito eggs.

Homing endonuclease genes

(HEGs). Selfish genetic elements encoding endonucleases that recognize a specific DNA sequence and catalyse a break, which is then naturally repaired through homologous repair.

Homology-directed repair

(HDR). A repair mechanism of a DNA double-strand break, whereby the homologous chromosome is used as a template for repair.

Non-homologous end joining

(NHEJ). A repair mechanism for DNA double-strand breaks, whereby the two DNA ends are ligated without the need for a homologous template, often resulting in small indels or the introduction of mutations.

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