The war against dengue fever has enlisted a tiny new ally: a cunning bacterium that inoculates mosquitoes against the virus that causes the debilitating disease.
The dengue virus hops from person to person via mosquitoes, so if the insects can’t carry the virus, disease transmission might be slowed or even halted.
That’s the hope of researchers racing to erase dengue, which infects 50 million to 100 million people worldwide each year in 100 mostly tropical countries, causing about 22,000 deaths, according to the World Health Organization. There is no vaccine available, and patients suffering the intense joint and muscle pain that mark a dengue infection have no treatment options other than painkillers. Growing resistance by mosquitoes to pesticides adds urgency to the battle against the virus.
That’s why researchers are hailing a promising field test in Australia reported Wednesday in the journal Nature.
In two isolated neighborhoods near Cairns, Queensland, researchers released batches of female mosquitoes deliberately infected with the protective bacterium, called Wolbachia. The bacterium, passing from mother to offspring, ripped through the mosquito population in the two neighborhoods, flipping entire swarms of the bugs from potential dengue carriers to dengue destroyers.
The test proved that deliberate introduction of Wolbachia can effectively spread the protective bacterium, said Scott O’Neill, the researcher at Monash University in Melbourne who led the project, called the Eliminate Dengue Program. “Wolbachia completely blocks the ability of dengue virus to grow in the mosquito,” he said. “If it can’t grow in the mosquito, it can’t be transmitted to people.”
During this year’s Australian wet season, which began in January, the researchers made 10 weekly releases of the dengue-resistant mosquitoes by driving through neighborhoods in a mosquito-carrying van. They then monitored the proportion of mosquitoes captured in each location that carried Wolbachia .
Even after they stopped releasing mosquitoes, the proportion they captured carrying Wolbachia continued to climb, reaching 100 percent in one location in three months and 90 percent in the other.
“I think it’s a huge deal,” said Jason Rasgon, a Johns Hopkins University researcher developing a similar strategy to battle malaria. “This strain of Wolbachia has the potential to spread worldwide and in theory eliminate dengue transmission.”
That’s because the bacterium is a cunning manipulator of insect reproduction. Somehow — scientists are unsure exactly how — females carrying Wolbachia reproduce more successfully than females that don’t carry it. This evolutionary strategy has been so successful that various strains of Wolbachia infect an estimated 70 percent of all insect species.
Strikingly, though, this evolutionary marvel does not naturally infect the species of mosquito that carries dengue virus, Aedes aegtypti.
So O’Neill and his colleagues set about finding a strain of Wolbachia that could infect Aedes aegypti while simultaneously protecting against dengue virus. They found that strain in their own back yard, inside Australian fruit flies.
Tests inside a mosquito-proof building proved this strain could rapidly spread through a small mosquito population. The team then sought and received approval from Australian government regulators to release the infected insects into the wild.
“We could tell everybody with a straight face that they already have this bacterium in their house,” said Michael Turelli, a University of California, Davis evolutionary biologist who collaborated with the Australians. “That helped get community buy-in.”
For at least two decades — since crucial observations made by Turelli — scientists have eyed enlisting Wolbachia in the war against mosquito-borne diseases. In the late 1980s, Turelli and a colleague discovered Wolbachia in fruit flies in Southern California orange groves. After observing the reproductive advantage the bacterium provided the flies, they watched Wolbachia “spread through California like wildfire.”
This rapid spread made a big scientific splash — inspiring researchers battling insect-borne diseases to search for Wolbachia strains that could protect against diseases.
That work is now poised to pay off against dengue fever. Meanwhile, other groups are racing to deploy Wolbachia against malaria and the bloodworm-caused tropical disease filariasis, which infects about 120 million people worldwide, causing a grotesque swelling of the limbs called elephantiasis.
At Johns Hopkins, Rasgon has successfully infected malaria-transmitting mosquitoes with a strain of Wolbachia that blocks the malaria parasite. But this Wolbachia does not carry to the offspring of infected females. “We’re not at the point where we can spread” the protective infection, Rasgon said.
Meanwhile, University of Kentucky researchers recently completed a field trial against filariasis on a small, uninhabited island in French Polynesia, said Stephen L. Dobson, the scientist who led that work. His strategy is slightly different: The strain of Wolbachia he deployed reduces the life span of mosquitoes, so it “acts like a pesticide,” said Dobson, and reduces mosquito populations.
“It’s safe to say we observed a significant impact,” said Dobson, who is preparing a scientific publication describing the work.
Dobson aims to start a trial in the United States within a year. This spring, he met with officials at the U.S. Agriculture Department and the Environmental Protection Agency. “They’re interested, and we’re essentially cocked and ready to go,” Dobson said. “It’s just a matter of making sure we meet all the regulatory requirements.”
The Australian team is now angling to start more rigorous tests in Vietnam, Thailand, Indonesia or Brazil — countries where dengue transmission is a much bigger problem than in Australia. There are so few cases of dengue fever in the Australian test areas that the researchers can’t yet claim to have reduced transmission of the disease, Rasgon said.
Still, Turelli said Wolbachia carries a huge potential for dramatically reducing or even eliminating tropical diseases. As demonstrated in Australia, small releases of Wolbachia-carrying mosquitoes can quickly blossom, expanding outward in a wave that replaces that existing population. Calculations that Turelli will publish next month in the journal American Naturalist show that flipping the mosquito population in a small area — one square kilometer — will start a Wolbachia wave that could blanket an entire country “in years, not decades,” he said.
“This is going to be a major industry,” Turelli predicted. “Many people are going to use Wolbachia to prevent the transmission of many diseases.”