Health
Potential solution to outbreaks of dengue fever, other mosquito-borne diseases awaits FDA approval
KEY WEST, Fla. — In late October, the U.S. Navy and U.S. Department of Agriculture tested insecticidal aerial spraying techniques over a warfare range in Jacksonville, Fla. The purpose: to evaluate how to lower populations of the blood-feeding Aedes aegypti mosquito, which transmits dengue fever.
Farther south, on the Treasure Coast, Florida health officials had a busy summer trying to control the most recent dengue fever outbreak. Some 22 people contracted the disease, known as break-bone fever for its debilitating joint pain and severe flu-like symptoms.
“It’s very difficult to spray everywhere where this mosquito hides and breeds,” said Gene Lemire, director of Martin County Mosquito Control. “It’s very sneaky.”
Officials admit they are having mixed results with conventional methods, such as fumigations and aerial spraying. The mosquito is tough to hunt down. It thrives in tropical metropolitan areas, moves indoors and can hide in closets, even in folds of laundry.
It’s something most people agree is a problem. But a different and controversial potential solution is splitting communities in the Sunshine State.
Michael Doyle is director of the Florida Keys Mosquito Control District (FKMCD). His job is to keep the 44 inhabited islands of the total 1,200 that spread across the Florida Straits free from Aedes aegypti mosquitoes. He wants to release genetically modified (GM) male mosquitoes, specifically designed to pass down a suicide gene that kills their own offspring, into the wild in hopes of bringing down the dangerous dengue-carrying mosquito population and preventing new outbreaks.
“We have tried everything from chemical fumigations to parasitic nematodes, dragonflies, everything you could think of,” Doyle said. Last summer the agency deployed a 2-pound drone, hoping the aircraft could help spot potential water breeding grounds in remote areas.
“We’re in an area with a year-round Aedes aegypti population,” Doyle said. “We need to reduce the mosquito population to low, low levels so that transmission of dengue is impossible.”
The infected female Aedes aegypti mosquito is the only one that bites and can transmit the dengue virus, along with other infectious diseases such as yellow fever and Chikungunya fever. The strategy has been to wipe out as many dengue vectors as possible to prevent the disease from taking hold in the human population.
But it may already be too late. Although dengue is considered rare in the U.S., some experts believe the recent cases in Florida are signaling the tip of the iceberg in terms of future outbreaks.
Effective abroad
In recent years, there has been a dramatic increase in dengue fever worldwide. It is estimated to infect from 50 million to 100 million people in metropolitan tropical cities.
In the U.S., probably no place is more vulnerable to a dengue outbreak than the Florida Keys, where the Aedes aegypti mosquito has been an invasive pest since the 16th century.
Yet when residents found out the mosquito control district was working with Oxitec, a British bioengineering company, to release hundreds of thousands of GM mosquitoes in their town, they were outraged.
Doyle explained that only male mosquitoes were altered, and they do not bite, so therefore they could not transmit diseases. Still, visions of mutant mosquitoes’ offspring that could survive and change a delicate ecosystem were rampant among residents.
Mila de Mier, a Key West real estate agent, started a petition last year opposing the GM mosquitoes. She has collected more than 125,000 signatures.
“I’m all for the experiment, but it has to be safe,” de Mier said. “Why can’t we have independent, peer-reviewed research to prove it?”
In 2009, Oxitec released 3.3 million GM mosquitoes in the Cayman Islands and published its results detailing a more than 80 percent mortality rate for mosquitoes in its test sites. The altered male insects passed down a lethal gene that, when inherited by their offspring, served as a death sentence for the progeny before adulthood. That experiment was criticized by organizations worldwide for being conducted without public consultation and independent oversight. Despite the uproar from environmental groups, Oxitec expanded its operations to Malaysia and Brazil.
This year, Brazil announced it was in the throes of an official dengue epidemic. Now a second, more ambitious collaboration with Oxitec is in the “ramp-up” stage of building a “mosquito plant” in the state of Bahia. Eventually, 4 million altered male mosquitoes will be released.
Biologist Margareth Capurro of Sao Paulo University is heading the second collaborative project with Oxitec and the Brazilian government. She said she knows that people were suspicious of Oxitec because it is a for-profit company, but she will have the independence to assess the experiments on her own.
“We have an agreement with Oxitec that I will evaluate the product independently,” Capurro said. “Is this the best that scientists can provide for this technology? No. The science is good, but we can improve things by finding ways to bring down the costs.”
Residents react
But far from the tropical city of Jacobina, Brazil, many Key West residents remain unconvinced that GM mosquitoes won’t survive and cause unknown problems. There hasn’t been a dengue outbreak in three years on the tiny island, so opponents wonder, why take the risk?
“Why not keep with the status quo and have more time for more studies?” de Mier said.
But Doyle, of the mosquito control district, says residents are not doing enough on their own to protect against mosquito proliferation.
“Unfortunately, when we go out to inspections we are continuously finding many containers with rainwater, and people aren’t being careful to empty them,” Doyle said. “It’s just not on people’s mind to empty containers with water or to use mosquito repellent.”
Joel Biddle was one of the Florida patients who contracted dengue in the 2010 outbreak. He admits he rarely uses repellent, but he does avoid standing near bromeliads after a rainstorm.
“I wish we could get away from the chemicals, but I’d rather stick with that until we know for certain what the long-term impact of those GM mosquitoes could be,” Biddle said. “It seems Oxitec is rushing to release something that hasn’t been adequately tested yet.”
But Oxitec says it can trace the mutant gene in the wild. Each GM insect is inserted with a fluorescent marker in the altered gene. It then becomes easily visible to the naked eye when the mutant gene is inherited in the offspring.
“As soon as we stopped releasing the mosquitoes, within two weeks, as we predicted, there is nothing in the environment that is left because males mate with the females and then they die; and their offspring is gone, too,” said Derric Nimmo, director of Oxitec Public Health Research.
Still, some object to Oxitec’s secretive research methods.
“Oxitec didn’t do themselves any justice by doing things clandestinely in Cayman,” said Phil Lounibos, distinguished professor at the University of Florida’s Florida Medical Entomology Laboratory. “If we can believe their evidence, and if the goal is to reduce the risk of dengue, can the GM mosquitoes reduce the native number of vectors to reduce the risk of dengue?”
“Yes, absolutely,” said Capurro, the Brazilian researcher. “No one knows at what level the population of the mosquitoes must be to ensure dengue can’t be transmitted. In the first trials, we saw a decrease in the mosquito population by 90 percent in two test districts, and that’s very good.”
Changing course
Anthony James, a distinguished professor at the University of California, Irvine, has researched the international regulatory process of GM mosquitoes and advises the Food and Drug Administration (FDA). James said that as bioengineering technology advances worldwide, more ground rules are needed in host countries to regulate GM insects.
“The science is really good, but I never would have done it like it was (done) in Florida,” he said. “First, community engagement is very specific to each region, and what works in Brazil won’t be the same in Florida. Another problem is, the U.S. is a patchwork of people, and nobody wants to take primary responsibility for regulating this.”
But if mistakes were made by not informing the Key West residents sooner, Doyle said the mosquito control district is paying attention now. Last year, the Key West City Commission passed a resolution objecting to the release of GM mosquitoes in the town until more research is available.
Doyle said he listened to the complaints and changed the trial site to Key Haven and Stock Island, two areas outside Key West with high Aedes aegypti populations. But instead of pacifying opponents, the move had the opposite effect.
“Stock Island has a large immigrant community, with trailer homes and not a lot of English speakers,” said de Mier, the activist. “Key Haven homes are spread out, expensive and more isolated. It seems the mosquito people just want to find a place where they won’t have a lot of protesters.”
“This is safe, and it’s been proven,” Doyle said. “In terms of allergenicity and health issues, the FDA is looking into that, so I put it in their hands.”
At a recent community meeting, when de Mier relayed her story of how she went twice to the Washington offices of the FDA to deliver her petitions in person, she received cheers from the audience. The first time, she said, the FDA destroyed her documents.
“The FDA people said they shredded my petitions because they thought the box they were in contained real GM mosquitoes, so the next time I went I had even more signatures,” de Mier told the crowd. The anti-FDA sentiment in the room was palpable.
But the residents weren’t the only ones frustrated with the process.
“We want people to trust we’re doing it right,” said Oxitec’s Nimmo. “We’ve been talking to the FDA, quite frankly, telling them here’s the information about our technology, here’s how it works, how are we going to regulate this?”
‘Watching every move’
At the beginning of the year, the Florida Keys Mosquito Control District conducted informal surveys and hired an independent outfit to survey the attitudes of Keys residents. In some answers, more than half the respondents supported GM technology to control mosquitoes.
“I don’t think the survey means much, because if you ask people if they want GM mosquitoes in their neighborhood, they will say no,” de Mier said. “Before, people didn’t know DDT was bad and we used that to kill mosquitoes. A lot of people just don’t trust the FDA and this private company to tell us the truth, because we don’t know what the long-term effects are yet.”
But whether the technology will get off the ground in the Keys will depend on the FDA decision, Doyle said. He has assured residents he won’t proceed without the agency’s approval.
“Technically, I think he can do it without their approval, but if the mosquito people do go on with this, we have an attorney and we will ask who will take responsibility if something goes wrong,” de Mier said. “We’re going to be watching every move they make.”