Alternative strategies for mosquito-borne arbovirus control

Abstract

Background: Mosquito-borne viruses-such as Zika, chikungunya, dengue fever, and yellow fever, among others-are of global importance. Although vaccine development for prevention of mosquito-borne arbovirus infections has been a focus, mitigation strategies continue to rely on vector control. However, vector control has failed to prevent recent epidemics and arrest expanding geographic distribution of key arboviruses, such as dengue. As a consequence, there has been increasing necessity to further optimize current strategies within integrated approaches and advance development of alternative, innovative strategies for the control of mosquito-borne arboviruses.

Methods and findings: This review, intended as a general overview, is one of a series being generated by the Worldwide Insecticide resistance Network (WIN). The alternative strategies discussed reflect those that are currently under evaluation for public health value by the World Health Organization (WHO) and represent strategies of focus by globally recognized public health stakeholders as potential insecticide resistance (IR)-mitigating strategies. Conditions where these alternative strategies could offer greatest public health value in consideration of mitigating IR will be dependent on the anticipated mechanism of action. Arguably, the most pressing need for endorsement of the strategies described here will be the epidemiological evidence of a public health impact.

Conclusions: As the burden of mosquito-borne arboviruses, predominately those transmitted by Aedes aegypti and A. albopictus, continues to grow at a global scale, new vector-control tools and integrated strategies will be required to meet public health demands. Decisions regarding implementation of alternative strategies will depend on key ecoepidemiological parameters that each is intended to optimally impact toward driving down arbovirus transmission.

Fig 1. WHO VCAG overview of new vector control product classes and status of evaluation.

Available from: http://apps.who.int/iris/bitstream/handle/10665/274451/WHO-CDS-VCAG-2018.03-eng.pdf?ua=.

Fig 2. Principle of a gene drive.

(A) Initial integration of a gene drive construct into the mosquito genome: Cas9 and the gRNAs encoded in the transgenic construct prepared as a plasmid can serve as molecular scissors mediating their own integration into the genomic target site they cut. Asterisks represent the cut sites determined by the gRNAs (three gRNAs in this example). Homologous recombination-mediated knock-in of the transgenic cassette occurs thanks to the target site flanking sequences cloned into the plasmid. (B) Spread of the gene drive in a mosquito population: mating between transgenic and nontransgenic mosquitoes places the transgenic construct in the presence of wild-type chromosomes that get cut by Cas9 at the target site determined by the gRNA(s). This break is repaired most frequently by homologous recombination with the intact chromosome, effectively copying the trans-gene into the broken wild-type chromosome and converting a heterozygous into homozygous cell. Cas9, CRISPR associated protein 9; gRNA, guide RNA.

Fig 3. Current and alternative arbovirus control methods in the context of the targeted life stage of implementation and anticipated impact on IRM.

IGR, insect growth regulator; IRM, insecticide resistance management; RIDL, release of insects with dominant lethality; ULV, Ultra-low volume spraying].