Fighting mosquitoes with more mosquitoes

Patti Sprague is playing the world's longest game of hide and seek.

Traversing fences, shimmying under houses and tramping through the leafy, lush backyards of Florida's Key West, Sprague has one target: mosquitoes. Sprague has been an inspector with the Florida Keys Mosquito Control District since 2011, where she's on the front lines of a battle against one of the world's deadliest creatures.

The mosquitoes in the Keys are mainly just a nuisance, except for one kind: Aedes aegypti, a non-native species that carries maladies including dengue fever and chikungunya. Typically tropical diseases, dengue and chikungunya infect as many as 400 million people worldwide; dengue alone has surged 30-fold in the last 50 years, according to the World Health Organization. And with climate change and increased travel and trade, it's posing threats even in areas where it was thought to be wiped out, including the U.S.'s southernmost points.

"Dengue is kind of this sleeper disease; It can exist in these low levels without us even knowing it, and then flare up," entomologist Michael Doyle, director of the Florida Keys Mosquito Control District, said in an interview. "We want a structure in place, so five years down the road, if there is dengue coming into the Keys in large numbers, we won't have the mosquitoes to spread anything."

Dengue's usually not fatal, though its effects can sometimes be so painful the malady has been dubbed "breakbone fever." It hospitalizes 500,000 people each year, sometimes overwhelming hospitals in developing countries. And in its severest forms, it does kill: dengue is responsible for 22,000 deaths annually, mostly in children, according to the WHO.

In 2009 and 2010, Florida's Keys saw some of the first outbreaks of dengue fever in the U.S. in decades, and since then has kept further infections at bay. Current methods require the constant vigilance of people like Sprague, who scours the same square mile of Key West over and over, hunting mosquitoes where they breed: standing water.

"Even though your house might be perfect, absolutely no standing water, no place where mosquitoes can actually breed, your neighbor unfortunately might have a saucer, a cat dish, that they haven't changed and it's breeding like crazy," Sprague said during a recent scouting trip through Key West.

The Florida Keys Mosquito Control District uses pesticides and other means, including introducing fish to ponds and other water sources, to keep the mosquito population down. It spends about $1 million a year solely on controlling the Aedes aegypti mosquito, about 10 percent of its budget—for a mosquito that makes up 1 percent of all seen in the Florida Keys, Doyle said. It's managed to cut numbers by about half—"and, quite honestly, that's considered good," he said.

But it's not enough to eliminate the threat of dengue and chikungunya, and the organization has turned to a new tool to try to reach that goal: releasing mosquitoes genetically modified to destroy their own kind.

It's a technology that's never been tried in the U.S., but it's been shown to reduce Aedes aegypti populations by as much as 90 percent in Brazil and the Cayman Islands, according to Oxitec, the small, private British biotechnology company behind the approach.

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"Our technology works by targeting the one insect species that's actually causing a problem," Oxitec CEO Hadyn Parry said in an interview. "So we've created a strain of Aedes aegypti which contains a gene which means the next generation don't survive."

Oxitec releases genetically modified male mosquitoes to mate in the wild. The eggs produced as a result die off. If Oxitec releases enough mosquitoes in an area, they overwhelm the bugs in the environment and eventually the whole population collapses.

Doyle said the technique appeals to him because it essentially uses mosquitoes to fight against themselves.

"Everything else that we do is getting a chemical or a granular or a liquid to the mosquito in a high enough amount that it kills them," Doyle said at his office in Key West. "At the same time, the mosquitoes are hiding, physically hiding. And they're developing resistance to our chemicals and finding new behaviors to avoid us, so there's this cat-and-mouse game that's been going on for centuries."

Oxitec is awaiting approval from the Food and Drug Administration to start a trial in a small area of the Keys, called Key Haven. Because it's a brand new technology, an entirely new regulatory path must be established for it. The FDA said it's reviewing the application "in consultation with government experts," and won't support a release of the mosquitoes until it's completed its review and assessed environmental impacts.

The plan has been met with local opposition. A change.org petition against the release of the mosquitoes has garnered more than 150,000 signatures, citing concerns about the impact of agenetically modified bug on the environment and ecosystem in the Keys.

"Nearly all experiments with genetically-modified crops have eventually resulted in unintended consequences," the petition says. "Why would we not expect GM (genetically modified) insects, especially those that bite humans, to have similar unintended negative consequences?"

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Oxitec's Parry says the company releases only male mosquitoes; only the females bite.

"We're only targeting the one insect that is causing the disease," Parry said. "So if you imagine going into a town with a chemical spray, you actually kill a lot of insects—some beneficial, some not beneficial, some nuisance and, you hope, some of the ones that spread disease. But with ours, you're only actually targeting that one species that's spreading disease, that's giving you the concern. So it's a much more targeted and precise method."

The technology also includes a method of tracking the reach of the genetically modified bugs, carrying a fluorescent protein that acts as a colored marker in the offspring. And as the Aedes aegypti only fly about 100 yards in their lifetime, "by virtue of that color you can actually see the distribution in the town," Parry said.

As Oxitec awaits the FDA's go-ahead, it's already received initial clearance in Brazil, a dengue hotspot. And mosquito experts there have a particular urgency: controlling the bugs before Rio de Janeiro swells with visitors next year for the summer Olympics.

"It's a huge focus," Doyle said. "Having that many people from that many countries in a tropical area all crowded together is a huge concern. And I'm sure the government is working very hard to get rid of all these mosquitoes if they can before the Olympics."

As Oxitec and others work on new means to control mosquito populations, drug companies are attacking the problem from another angle. Sanofi, Merck and Takeda Pharmaceutical are developing dengue vaccines, with Sanofi having just finished the last stage of testing before applying for regulatory approval.

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"This was the first time ever that a vaccine actually showed efficacy to prevent dengue," said Fernando Noriega, head of clinical development for Sanofi Pasteur's dengue program in Latin America. "It took us over 20 years to come out with a vaccine that was this effective against dengue."

Sanofi plans to file for approval this year, and Noriega said the vaccine may start to be used in the most affected countries by the end of 2015.

In areas like the Keys, which has seen dengue but kept it at bay, it's a daily battle: man versus mosquito.

"These are my people," mosquito control inspector Sprague said, driving through the streets of Key West. "I don't want them to get bitten."