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Fighting dengue with "family planning" for mosquitoes
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09:17, July 15, 2009

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The scourge of dengue fever might be cut by neutering the mosquitoes that carry it. Call it family planning. Males are genetically engineered so that when they mate with females, their offspring never surpass the larval stage of development.

While the idea is nothing new, it is the first time such an approach is being used to develop male-sterile Aedes aegypti, the type of mosquito that carries yellow fever, chikungunya, and dengue fever.

The World Health Organizations (WHO) estimates that approximately two-fifths of the world's population -- 2.5 billion people -- are now at risk from the dengue virus, primarily in South Asia and Latin America.

But recent reports show that the tropical disease has increased30-fold over the past 50 years, especially as temperatures warm in typically cool regions, such as in North America.

In an attempt to address what is already an endemic in some parts of the world, a team of researchers at Oxitec, based in Oxford, the United Kingdom, has created a Genetically Modified (GM)A. aegypti mosquito designed to compete with wild-type mosquitoes. If all goes well, the GM version will eventually lead to a reduction in dengue-carrying mosquitoes.

Controlled testing has already begun in Malaysia and, pending regulatory approval, authorities are expected to release the organisms into the wild.

But not everyone is buzzing with excitement. A concerned group of citizens in the South Asian country fear they are being subjected to an experiment where all the risks are not immediately apparent.

The first open-field testing of GM mosquitoes has many fearing that Oxitec and the Malaysian government will lose control over its creation, creating a Frankenstein-mosquito.

A SELF-LIMITING TECHNOLOGY

Oxitec's head of business development Ann Kramer told Xinhua in a recent interview by phone that, unlike other GM mosquitoes being developed by academic groups, Oxitec's mosquito will be unable to spread its genetically altered traits throughout the environment.

"With our approach, they will be released, they will die, and their progeny will die so there will always be the ability to take it at a speed we control," she said from her office in Oxford. "We can decide, rather than run the risk of things going faster than we had perhaps planned."

The John Hopkins Group in Maryland, for example, is currently working on a GM Anopheles mosquito that is resistant to the malaria parasite. In theory, the genetic trait will be passed on through reproduction in an attempt to dominate the mosquito population and reduce infection rates.

The Sterile Insect Technique (SIT) that Oxitec employs has been around for decades. In the United States and Mexico, authorities used the method to eliminate the New World screw-worm by about 1985.

And in China, there could be future possibilities for the technique. Kramer said the Ministry of Agriculture has contacted Oxitec about using their approach to combat the Oriental fruit fly, which is threatening China's citrus agriculture.

But up until recently, the SIT seemed doomed to fail in A. aegypti mosquitoes because, in part, the radiation for sterilization is extremely damaging. To address the issue, Oxitec has developed a sterile male version which does not need to be irradiated and produces late-acting lethality in its larvae.

"In the past, that has not been possible," said Kramer, noting that the Indian government has also begun testing the Oxitec technology in labs in Chennai.

"BREAK BONE"

In the past, the dengue virus typically spread as a result of a monsoon or tropical weather. But that appears to be changing. Countries around the world say that the virus is on the rise, from Vietnam to the United States.

Last week, a New York-based nonprofit environmental group reported that two types of mosquitoes capable of transmitting the virus -- the predominantly urban species A. aegypti and the Asian tiger mosquito -- have been found in 28 U.S. states and may travel further around the country as temperatures rise.

Climate change could push the traditionally tropical disease into the far corners of the United States, where dengue-carrying mosquitoes have typically been rare.

According to the WHO, cases of dengue have reached unusually high rates in the past four years, with 50 million infections worldwide every year.

Dengue, or "break bone," fever can be caused by any one of the four types of dengue virus. A person can be infected by at least two, if not all four types at different times during a life span, but only once by the same type.

Sometimes, dengue infections lead to hemorrhagic fever, a potentially lethal complication that has become a leading cause of hospitalization and death among children in Asia, according to the WHO.

Marked by the severe onset of a fever of 103 to 105F, or around 40C, victims suffer from pain behind the eyes, muscle and joint pains, skin rash, diarrhea and vomiting.

With no cure or vaccine in sight, the WHO has stated that the only way to prevent virus transmission is to attack the mosquitoes themselves.

THE ULTIMATE EXPERIMENT

So far, Oxitec's GM A. aegypti looks promising, said Kramer. Malaysia's medical research center has tested the sterile bugs in physically contained semi-field trials in a simulated three-room Malaysian dwelling.

Among a host of other concerns, researchers are primarily interested in whether the GM mosquito is able to compete with local males to win the female over and impregnate her with the never-to-be-born offspring.

"Our strain performed very well," said Kramer. "It competed very well with the local, wild Malaysian mosquitoes."

But before the Malaysian government can conduct open-field trials, a slew of national regulatory agencies must give their approval.

Dr. Yeya Toure, who leads vector research in the WHO Tropical Diseases Department (TDR), and a group of experts from around the world have begun creating regulatory standards in a framework designed to assist developing countries develop technical, safety and ethical review of trials involving GM insects.

"What the WHO and TDR want to do is to provide guidance to countries for addressing an issue that holds both potential for human health benefits and also some risks," Toure told Xinhua in a statement. "WHO, TDR and its partners intend to help countries getthe necessary guidance (so they can be) better prepared to make their own assessment and decision."

As with all GM testing, researchers are aware of public concerns about health and the environment. Oxitec has conducted several small focus groups in Malaysia, said Kramer, noting that the people they spoke to were receptive to the idea of a sterile mosquito that could reduce the rate of dengue infections.

But not everyone is convinced. Cheah Hooi Giam, an optometrist who lives in Malaysia, started an online petition demanding that the Malaysian government take full responsibility and make itself liable for any problems that may arise from the release of the GM mosquitoes.

Giam told Xinhua by e-mail that he is concerned his country is being taken advantage of by groups in the West looking to make a profit.

"Why should a developing country bear the brunt of being the site of a field trial for releasing genetically modified mosquitoes?" he asked. "If anything, developing countries are least able to handle an emergency if something should go wrong with the release."

Giam said he worried that the GM mosquito could mutate and become resistant to current methods of eradication like pesticides.

"A controlled environment can never be the same as the real environment," he said. "Nobody can give an assurance or know what will or will not happen in the real environment."

But Kramer said Oxitec, which was spun off from Oxford University in 2002, is developing a technology that will benefit the developing world so "it's right and proper" that they be involved in the entire process.

"There is no market to make stack loads of money," she said. "It does not exist."

Oxitec, which receives partial funding for its SIT program from the Bill and Melinda Gates Foundation, estimates governments that want the technology will have to pay roughly one to three U.S. dollars per person -- roughly the same as mosquito bed nets.

Currently, the Malaysian government spends 130 million U.S. dollars a year on trying to control mosquitoes and on tending to those infected with the dengue virus, according to Kramer, who cited a report to be released shortly.

Going after A. aegypti is the best approach to a quickly-spreading disease, said Kramer. Insecticides only kill the mosquitoes present at that very moment and many people do not want insecticide sprayed in their homes.

Despite a high awareness that trash easily becomes breeding grounds for mosquitoes, Kramer noted that "in no country are they managing to clean up the mosquitoes well enough to prevent the spread of dengue."

Source: Xinhua



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