Infected Insects Fight Dengue Fever

It may sound like a far-fetched scheme: Infecting mosquitoes with a bacterium to prevent them from passing a viral disease to humans. But two studies published today show that the scenario might work. Researchers have infected Aedes aegypti mosquitoes with an odd microbe that makes the insects resistant to the virus that causes dengue fever; when scientists released these insects in two towns in Northern Australia, the bacterium spread rapidly. That suggests the strategy could help make entire mosquito populations permanently unable to sicken humans.

Many researchers are trying to tinker with mosquito populations to ward off human disease. They have created transgenic mosquitoes resistant to malaria, for instance, and released “genetically sterile” insects to help fight dengue, a disease that affects more than 50 million people annually and causes fever, rash, headaches, and crippling joint and muscle pains.

Dengue, for which no drugs or vaccines exist, is also the target of medical entomologist Scott O'Neill of Monash University in Australia, but he is using an approach in which mosquitoes are infected with Wolbachia pipientis, an intracellular bacterium.

Wolbachia naturally infects many insect species, and it has an aggressive tactic of interfering with its host's reproduction to ensure that entire populations become infected in just a few generations. A few years ago, O'Neill's team discovered that a virulent Wolbachia strain isolated from fruit flies could infect Ae. aegypti, a species that doesn’t normally host the microbe. For reasons not entirely understood, the infection almost completely blocked the mosquito's ability to transmit the dengue virus.

There was only one drawback: the virulent Wolbachia strain sharply reduced the mosquito's lifespan, making it unlikely that infected insects could outcompete their uninfected counterparts in the wild.

In one of two Nature papers published today, O'Neill reports that a much milder strain of Wolbachia also makes mosquitoes highly resistant to the virus, but without the effect on their lifespan. When the researchers placed mosquitoes carrying this Wolbachia strain in cages together with uninfected mosquitoes, all of the insects soon became infected.

Would the same happen in nature? To find out, the researchers started setting the mosquitoes loose in Yorkeys Knob and Gordonvale, two towns in northern Australia. They released between 10,000 and 20,000 mosquitoes a week in each location for about 10 weeks. The Wolbachia infection spread rapidly, exactly as the researchers had hoped, and it continued to expand even after they stopped releasing mosquitoes. Some 6 weeks after the last release, the infection rate was very close to 100% in both towns, the team reports in a second Nature paper.

The study was not set up to show an effect on dengue transmission, which occurs only sporadically in the area. The team is now discussing field tests with regulatory authorities in four dengue-endemic countries--Vietnam, Indonesia, Thailand, and Brazil--to see whether the mosquitoes can actually help prevent the disease. O'Neill says he's hopeful that the first study can start within a year. "We wanted to start in our own backyard," he says, to show that the mosquitoes are safe and avoid accusations that people in developing countries serve as guinea pigs.

"I think the future for this approach looks quite rosy," says medical entomologist Willem Takken of Wageningen University in the Netherlands. The approach has a big advantage over those using genetically engineered mosquitoes, he says, because it's less likely to run into regulatory bumps or political opposition. "This is a more elegant and more natural strategy." The fact that, once it's set loose, the infection will spread on its own also makes it an attractive option, Takken adds.