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  • Review Article
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Beyond insecticides: new thinking on an ancient problem

Key Points

  • Vector-borne diseases are on the rise globally. Although there have been some successes with vaccines and drug treatment, most of the current measures for limiting these diseases focus on vector control.

  • Habitat modification, insecticides, bed nets, biopesticides and sterile-male releases have all been used in the past, with some efficacy. There are also several emerging technologies that rely on genetic modification of the vector or bacterial symbionts for biological control of the vector.

  • Genetic modification approaches include release of insects carrying a dominant lethal (RIDL), homing endonuclease genes (HEGs) and RNAi, with RIDL being the most progressed of these three approaches and currently in the stage of open-field releases. In this approach, mosquito populations are reduced by releasing males carrying a transgene that renders their female offspring flightless.

  • The insect endosymbiont Wolbachia is being developed for control via three potential pathways: releasing male mosquitoes that are mating-incompatible with wild-type female mosquitoes to reduce or eliminate populations, reducing the lifespan of the vector to reduce the number of insects able to transmit the disease, and reducing the ability of a range of pathogens to infect the insect. This latter approach is currently on trial in open-field release studies.

  • The roll out of all these methods will require substantial engagement with all stakeholders to ensure community and government support.

  • Each of the methods harbours risks around long-term stability and the evolution of resistance. These potential drawbacks will only truly be tested by monitoring the efficacy of the approaches following their implementation. As with other interventions, combinations of these approaches with more traditional control practices, such as the use of insecticides, vaccines and drug therapy, might offer the best solution for long-term disease control.

Abstract

Vector-borne disease is one of the greatest contributors to human mortality and morbidity throughout the tropics. Mosquito-transmitted diseases such as malaria, dengue, yellow fever and filariasis are the main contributors to this burden. Although insecticides have historically been used to try to control vector populations, over the past 15 years, substantial progress has been made in developing alternative vector control strategies ranging from biocontrol methods through to genetic modification of wild insect populations. Here, we review recent advances concerning these strategies and consider the potential impediments to their deployment, including the challenges of obtaining regulatory approval and community acceptance.

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Figure 1: Vector-borne diseases are a global problem.
Figure 2: Genetic modification approaches for vectors.
Figure 3: Vector control using Wolbachia.

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Acknowledgements

The authors are supported by grants from the Foundation for the US National Institutes of Health (through the Grand Challenges in Global Health Initiative of the Bill and Melinda Gates Foundation), the National Health and Medical Research Council of Australia and the Queensland State Government.

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FURTHER INFORMATION

Eliminate dengue

Oxitec

Glossary

DALY

(Disability-adjusted life year). The number of years lost owing to morbidity or mortality of a disease. This measure is preferable to simple mortality measures, as it better captures the disease burden for debilitating but often self-limiting diseases like dengue and malaria.

Brackish

Slightly salty; pertaining to water such as that present in estuaries.

Anthropophilic

Preferring humans over other animals as a blood meal source.

Copepods

Small freshwater crustaceans (in the context of this Review, of the genus Mesocyclops) that prey on mosquito larvae.

DDT

(Dichlorodiphenyl-trichloroethane). An organochlorine-based insecticide that has been used since the Second World War to control insects. The insecticide is banned in some countries because of its potential ill effects on human health and non-target species, but it is still used intensively in Africa in regions of high malaria transmission.

Transgenes

Genes or genetic material that has been introduced into another organism using genetic engineering techniques.

RNAi

The process by which animals cleave double-stranded RNAs into small fragments, the presence of which directs transcriptional silencing of the corresponding gene. RNAi also has a role in immunity, as it is responsible for cutting and degrading the RNA of invading viruses.

Cytoplasmic incompatibility

The failure of embryo development in the early stages, as the result of a Wolbachia-infected male mating with an uninfected female. This leads to poor or no survival of the offspring. By contrast, when two Wolbachia-infected adults mate, the egg of the infected female 'rescues' Wolbachia-mediated changes to the sperm and allows the offspring to develop normally.

Transinfect

To transfer a bacterial or viral infection from one host to another by microinjection.

Bidirectional incompatibility

A phenomenon that occurs when mating males and females are infected with different Wolbachia strains. Eggs from the female may not be able to rescue the Wolbachia-induced changes in the sperm of the male. The consequence is an incompatibility in the embryo such that few or no offspring survive, despite the fact that both parents carry Wolbachia.

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McGraw, E., O'Neill, S. Beyond insecticides: new thinking on an ancient problem. Nat Rev Microbiol 11, 181–193 (2013). https://doi.org/10.1038/nrmicro2968

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