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Mosquito Birth Control

by Jeff Worley

Photo of mosquitoIt sounds like the plot of a horror flick. Mosquitoes on some distant tropical island bite people and deposit worms in their blood. These worms grow and mate inside the victim, and the adult female worms produce thousands of larval worms that circulate in the blood. The worms can block and damage the lymph system, which can result in swelling of the legs and other extremities. This swelling, known as “elephantiasis,” is not fatal, but results in severe disability and social stigma. Welcome to the very real-world scenario of human lymphatic filariasis.

Human filariasis, a close relative of the dog heartworm, affects only humans. This is a globally important disease, occurring in 80 countries. Currently, 120 million people have filariasis, 40 million people are seriously incapacitated, and 1.2 billion people are at risk, according to Stephen Dobson, an associate professor of entomology in the University of Kentucky College of Agriculture.

When Dobson talks about filariasis, his expression turns solemn; his words precise and direct. Photographs mounted in the hallway outside his office constantly remind him of the importance of his mission: children with elephantiasis, their legs swollen to four times their normal size, toes completely encased in a red glove of their own skin. And a huge blown-up photo of his arch nemesis—Aedes polynesiensis—landing on human flesh with its six stilt-like legs, the hungry needle protruding from its face dipping down to feed.

The scientists heading up this project envision a 1-2 punch to eradicate this disease. The first strike will be a massive campaign to treat the entire at-risk population with the potent drugs diethylcarbamazine and albendazole, both of which have been used to treat other worm diseases. Albendazole works by keeping the worm from absorbing sugar (glucose), so that the parasite loses energy and dies. The drugs have been donated to this project by several major pharmaceutical companies.

“The initial strategy is give drugs to everyone in the affected areas,” says Dobson, who came to UK after doing postdoc work at Yale for two years. “These pills are analogous to the yearly treatment given to dogs for heartworm in the United States—each person takes one dose a year.” The pills kill the immature worms, but not the adult worms, which live in the human lymphatic system for up to five years. So to stop the transmission cycle, the entire population must take the pills for at least five years to prevent new infections, while waiting for the adult worm to die of old age.

Photo of Stephen Dobson“But here’s the problem: we know that lymphatic filariasis transmission cannot be stopped in some areas using drugs alone. On some South Pacific islands, for example, drug treatment has continued for decades, yet the disease persists.” One explanation, Dobson says, is insufficient participation in the drug program—if people experience strong side effects after taking the pills, they are less likely to take them the next year. “So in conjunction with this strategy, our approach is to help break the transmission cycle by targeting the mosquito population.”

To do this, he and his team are using Wolbachia, a type of bacterium that infects arthropods and that can significantly damage the reproductive capabilities of its hosts. “We hope to sterilize the mosquito population by releasing many Wolbachia-infected males.” (Only female mosquitoes bite and transmit disease.) Sterility will cause the mosquito population to dwindle.  In the next generation, continued releases of sterile males into the smaller mosquito population results in even more sterility, due to the higher ratio of sterile to fertile males, and as this process is repeated, eventually the last female mates with a sterile male, and “it’s ‘game over’ for the mosquito,” Dobson says.

He has shown that this approach works in the lab, so now what?

“The next step is to test the strategy in field conditions,” he says.  He and his team are currently building large outdoor cages in French Polynesia, cages which will be populated with mosquitoes collected from the field. The researchers will then release sterilized males into the cages to see if they can survive and compete with normal males for mates. “The long-range goal is to be able to suppress these mosquito populations in areas where they cause tremendous human suffering.”

In a related project, Dobson is the U.S. representative on a team of scientists from Australia, Thailand, Vietnam, and Japan leading a campaign to improve methods to control mosquitoes that transmit the dengue virus. This tropical disease can result in high fever, severe muscle and joint pains, and death. Similar to human filariasis, new dengue infections can be transmitted only by mosquitoes. The project is funded by a $10 million grant from the Bill and Melinda Gates Foundation, as part of its Grand Challenges in Global Health initiative.

Dobson was chosen to lead the U.S. part of this research because of his groundbreaking work at UK creating new Wolbachia infections in mosquitoes, including Aedes aegypti, the main carrier of dengue and yellow fever. The researchers do this by injecting mosquito eggs with a strain of Wolbachia that passes from mother to offspring. Once established, the infection can spread without assistance into the mosquito population through a mechanism called “cytoplasmic incompatibility,” the same mechanism used to make mosquitoes sterile in the filariasis project.

“Dobson’s work is a significant step towards completely replacing a population that can transmit dengue with one that can’t,” says Steven Sinkins, quoted in a New Scientist article in October 2005. Sinkins studies Wolbachia at the University of Oxford in England.

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