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A Ray of Sunshine in the Fight Against Dengue

A long-held dream in medical entomology has been to use genetic strategies to replace populations of a mosquito vector with mosquitoes of the same species that are incapable of pathogen transmission. A prime target for this strategy has been the replacement of wild, pathogen-competent Aedes aegypti with Ae. aegypti that are incapable of transmitting dengue viruses (DENV serotypes 1, 2, 3, and 4).

Hoffman et al. (2011) have used Wolbachia pipientis, a bacterium they obtained from the fruit fly, Drosophila melanogaster, as a vehicle to successfully accomplish one part of this long sought goal. Prior studies showed that this particular strain of Wolbachia, called wMel, had the capability of interfering with dengue transmission by Ae. aegypti that had been infected with the bacterium and then infected with DENV without substantial reduction in the competitive fitness of the Wolbachia-infected mosquitoes. This made for an excellent prospect for a successful dengue control strategy.

Wolbachia have long been studied because they provide excellent vehicles for such a population replacement strategy. These bacteria have the capability of spreading through natural insect populations on their own. This can be accomplished artificially by releasing a few Wolbachia-infected individuals of selected insect species into natural populations. The spread of Wolbachia through a population is due to host cytoplasmic incompatibility caused by Wolbachia itself. The embryos of non-Wolbachia infected host females die when these females mate with a Wolbachia-infected male. Wolbachia infected females do not suffer at all and can mate with both uninfected and Wolbachia-infected males. Since Wolbachia are passed from females to their offspring through maternal inheritance, there is a mating bias favoring females with Wolbachia-infected offspring. The Wolbachia-infected insects increase while uninfected insects decrease in frequency and Wolbachia spreads rapidly through the population.

A major step forward in implementing this strategy for DENV and Ae. aegypti is the report of the first field test that demonstrates the release of wMel Wolbachia-infected mosquitoes will spread through an Ae. aegypti population and rapidly replace the field population with wMel Wolbachi- infected mosquitoes that should not be susceptible to infection with DENV (Hoffman et al. 2011). During a 10 week period the authors released 141,600 wMel Wolbachia-infected adult Ae. aegypti at one location and 157,300 wMel Wolbachia-infected adults at a second site in northeastern Australia. Trapping demonstrated that the frequencies of Wolbachia-infected Ae. aegypti at both locations reached 100% and continued well after the releases were discontinued. It works!

This is the first demonstration of the potential for this novel strategy in the fight against DENV. Certainly, if successful, this strategy could be used for other vector-borne pathogens if suitable naturally or artificially constructed Wolbachia populations can be found that interrupt vector transmission of the particular pathogen. There is much more that needs to be done before this strategy can be widely used in actual dengue control. Even though wMel Wolbachia spread easily through a natural Ae. aegypti population, further testing will be needed to assure that the Wolbachia-infected mosquitoes maintain the desired trait in nature and cannot transmit DENV. Further tests will also be needed to assess how the wMel Wolbachia interacts with other Ae. aegypti populations elsewhere in the world to ensure that it spreads and has the desired effect of interrupting local DENV transmission in other areas of the world. Finally wMel will have to be assessed against all the other DENV serotypes under a variety of laboratory and field conditions.

This work represents a great step forward. Just think about a future where the threat of DENV from Ae. aegypti in a place like Key West is no longer a concern. Consider that it is now within the realm of possibility to change the Ae. aegypti populations in Key West, rendering them ineffectual disease vectors, by using a low cost release of Wolbachia-infected Ae. aegypti. Then all mosquito control would have to deal with is to prevent these mosquitoes from being pests and biting people!

Reference
Hoffman, A. A. et al. 2011. Successful establishment of Wolbachia in Aedes populations to suppress dengue transmission. Nature 476: 454-457.

   Walter J. Tabachnick and Jonathan F. Day
   Department of Entomology and Nematology
   Florida Medical Entomology Laboratory
   University of Florida IFAS
   Vero Beach, Florida