Wolbachia as translational science: controlling mosquito-borne pathogens

Flaviviruses are vector-borne RNA viruses that can emerge unexpectedly in human populations and cause a spectrum of potentially severe diseases including hepatitis, vascular shock syndrome, encephalitis, acute flaccid paralysis, and congenital abnormalities and fetal death. This epidemiological pattern has occurred numerous times during the last seventy years, including epidemics of Dengue virus and West Nile virus, and the most recent explosive epidemic of Zika virus in the Americas. Flaviviruses now are globally distributed and infect up to 400 million people annually. Of significant concern, outbreaks other less well-characterized flaviviruses have been reported in humans and animals in different regions of the world. The potential for these viruses to sustain epidemic transmission among humans is poorly understood. In this Review, we discuss the basic biology of flaviviruses, their infectious cycles, the diseases they cause and underlying host immune responses to infection. We describe flaviviruses that represent an established ongoing threat to global health and those that have recently emerged in new populations to cause significant disease. We also provide examples of lesser known flaviviruses that circulate in restricted areas of the world but have the potential to emerge more broadly in human populations. Finally, we discuss how an understanding of the epidemiology, biology, structure, and immunity of flaviviruses can inform the rapid development of countermeasures to treat or prevent human infections as they emerge.

Complete population collapse of malaria vector Anopheles gambiae in cages is achieved using a gene drive that targets doublesex. Supplementary information The online version of this article (doi:10.1038/nbt.4245) contains supplementary material, which is available to authorized users.

The radiation-based sterile insect technique (SIT) has successfully suppressed field populations of several insect pest species, but its effect on mosquito vector control has been limited. The related incompatible insect technique (IIT)-which uses sterilization caused by the maternally inherited endosymbiotic bacteria Wolbachia-is a promising alternative, but can be undermined by accidental release of females infected with the same Wolbachia strain as the released males. Here we show that combining incompatible and sterile insect techniques (IIT-SIT) enables near elimination of field populations of the world's most invasive mosquito species, Aedes albopictus. Millions of factory-reared adult males with an artificial triple-Wolbachia infection were released, with prior pupal irradiation of the released mosquitoes to prevent unintentionally released triply infected females from successfully reproducing in the field. This successful field trial demonstrates the feasibility of area-wide application of combined IIT-SIT for mosquito vector control.