Mosquitoes armed with bacteria beat back dengue virus

NATIONAL HARBOR, MARYLAND—In a handful of cities around the world, mosquitoes have been armed with a microscopic weapon against disease. The bacterium Wolbachia pipientis blocks the insects’ ability to spread fearsome viruses such as dengue, Zika, and chikungunya. Since 2011, researchers have been injecting Wolbachia into the eggs of Aedes aegypti mosquitoes and releasing the hatched insects, which spread this protection to their offspring. But the field has been waiting for evidence that this approach actually reduces disease in people.

Signs that it does came this week in preliminary results from several trials in tropical areas burdened with mosquito-borne viruses such as dengue. In some release areas, studies conducted by the nonprofit World Mosquito Program (WMP) found as much as a 76% reduction in the rate of dengue, which causes fever and severe joint pain and has no specific treatment.

“The first indications are very promising,” says Marcelo Jacobs-Lorena, a geneticist at Johns Hopkins University in Baltimore, Maryland, who wasn’t part of the studies.

Wolbachia naturally inhabits many insects, though not A. aegypti. In mosquito cells, the bacterium can prevent viruses such as dengue from replicating—and thus from spilling into a new host when a mosquito bites. Proponents say the approach could complement traditional methods such as insecticide sprays, which often fail to control disease. And because the bacterium spreads on its own, it could be more cost effective than population-reducing approaches such as genetic engineering, some of which require ongoing releases.

WMP researchers reported this summer that in more than 4 years after a trial release of infected mosquitoes in Townsville, Australia, only four locally acquired cases of dengue were recorded. No previous period of that length since 2001 had fewer than 69 cases.

But stronger evidence of Wolbachia’s impact requires comparing rates of disease in release areas with those at untreated sites nearby. At the annual meeting of the American Society of Tropical Medicine and Hygiene here this week, WMP epidemiologist Katie Anders of Monash University in Melbourne, Australia, presented results from such controlled trials on opposite sides of the globe. On the outskirts of Yogyakarta, Indonesia, local health officials documented 76% fewer dengue infections in the 2.5 years after the release of Wolbachia mosquitoes than in a nearby control area. And one treated area in Niterói, Brazil, saw 75% fewer chikungunya cases than untreated sites. (A reduction in dengue cases was harder to evaluate because rates were generally low during the trial.)

Those results rely on public health surveillance data, which can include inaccuracies and misdiagnoses, Anders acknowledged. But, “We’re still seeing a signal,” she said, and seeing it across sites “is giving us confidence.”

It isn’t always easy to get Wolbachia to spread and remain in wild mosquito populations. WMP infectious disease researcher Cameron Simmons, also at Monash University, noted that levels of the bacterium unexpectedly dropped in one study area in Vietnam. Heat may have contributed; lab tests suggest A. aegypti larvae that develop in hotter environments have lower Wolbachia levels.

Another team of researchers is releasing and tracking a different Wolbachia strain that may better resist high temperatures. Steven Sinkins, a vector biologist at the University of Glasgow in the United Kingdom, and his collaborators have been releasing infected mosquitoes in and around apartments, houses, and shopping areas in Kuala Lumpur. In a pilot study of six release sites, published this week in Current Biology, Sinkins’s team reported a 40% reduction in dengue cases compared with similar sites with no releases.

Both teams are now conducting larger trials. In central Yogyakarta, WMP has carved out 24 randomized release and control sites. From local clinics, they will identify patients with dengue and those with other causes of fever, then compare the proportions that live in Wolbachia-treated and control areas. That trial is the “gold standard,” says Fred Gould, an evolutionary biologist at North Carolina State University in Raleigh. If the results, expected next year, back up the preliminary evidence that Wolbachia reduces dengue, he says, the World Health Organization could approve this microbial ally for broader use.