Special mosquitoes are bred to combat dengue fever. How have old enemies now become allies?
TEGUCIGALPA, Honduras – For decades, preventing dengue fever in Honduras meant teaching people to fear mosquitoes and avoid their bites. Now, Honduran citizens are being educated about a more effective way to control the disease, which goes against everything they have been taught.
Which explains the joy of dozens of people last month when Tegucigalpa resident Hector Enriquez held a glass jar filled with mosquitoes above his head, then released the buzzing insects into the air. Enriquez, a 52-year-old construction worker, volunteered to help spread a plan to eradicate dengue fever by releasing millions of private mosquitoes into the Honduran capital.
Scientists bred mosquitoes that Enriquez released in his El Mancin neighborhood — an area rife with dengue fever — to carry a bacteria called Wolbachia that stops transmission of the disease. When these mosquitoes reproduce, they pass the bacteria on to their offspring, reducing future outbreaks.
This emerging strategy to combat dengue was pioneered over the past decade by the nonprofit Global Mosquito Program, and is being tested in more than a dozen countries. With more than half the world’s population at risk of dengue fever, WHO is paying close attention to mosquito releases in Honduras and elsewhere, and is ready to promote this strategy globally.
In Honduras, where 10,000 people are known to fall ill with dengue each year, MSF is collaborating with the mosquito program over the next six months to release nearly 9 million mosquitoes carrying Wolbachia bacteria.
“New approaches are urgently needed,” said Scott O’Neill, founder of the Mosquito Program.
Dengue challenges conventional prevention
Scientists have made great strides in recent decades in reducing the threat of mosquito-borne diseases, including malaria. But dengue fever is the exception: its incidence continues to rise.
Models estimate that about 400 million people in about 130 countries become infected with dengue each year. Mortality rates from dengue are low — an estimated 40,000 people die from it each year — but outbreaks can overwhelm health systems and force many people to miss work or school.
“When you get a case of dengue, it’s often like having the worst case of influenza you can imagine,” said Connor McMeniman, a mosquito researcher at Johns Hopkins University. This condition is commonly known as “break-bone fever” for a reason, McMeniman said.
Traditional methods of preventing mosquito-borne diseases have not been nearly as effective against dengue.
The Aedes aegypti mosquitoes, which commonly spread dengue fever, have been resistant to insecticides, which have transient results even in the best-case scenario. Because the dengue virus comes in four different forms, it is difficult to control with vaccines.
Aedes aegypti mosquitoes are also a difficult enemy because they are most active during the day – that is, when they bite – so mosquito nets are of little help against them. Because these mosquitoes thrive in warm, humid environments and densely populated cities, climate change and urbanization are expected to make combating dengue more difficult.
“We need better tools,” said Raman Velayudhan, a researcher with the World Health Organization’s Global Program on Neglected Tropical Diseases. “Wolbachia is definitely a long-term, sustainable solution.”
Velayudhan and other experts from the World Health Organization plan to publish a recommendation early this month to encourage further testing of the Wolbachia strategy in other parts of the world.
Scientists were surprised by bacteria
The Wolbachia strategy has been decades in the making.
The bacteria are found naturally in about 60% of insect species, but not in the Aedes aegypti mosquito.
“We’ve been working on this for years,” said O’Neill, 61, who with the help of his students in Australia eventually figured out how to transfer bacteria from fruit flies to Aedes aegypti mosquito embryos using microscopic glass needles.
About 40 years ago, scientists aimed to use Wolbachia bacteria in a different way: to reduce mosquito populations. Because male mosquitoes that carry the bacteria only produce offspring with females that also carry it, scientists release infected male mosquitoes into the wild to breed with uninfected females, whose eggs will not hatch.
But along the way, O’Neill’s team made a surprising discovery: mosquitoes carrying Wolbachia did not spread dengue — or other related diseases, including yellow fever, Zika, and chikungunya.
As infected females transmit Wolbachia to their offspring, they will eventually “replace” the local mosquito population with others carrying bacteria resistant to the virus.
Oliver Brady, an epidemiologist at the London School of Hygiene and Tropical Medicine, said the replacement strategy would require a major shift in thinking about mosquito control.
“In the past, everything was about killing mosquitoes, or at least preventing mosquitoes from biting humans,” Brady said.
Since O’Neill’s lab first tested the substitution strategy in Australia in 2011, the Global Mosquito Program has conducted experiments affecting 11 million people in 14 countries, including Brazil, Mexico, Colombia, Fiji and Vietnam.
The results are promising. In 2019, a large-scale field trial in Indonesia showed a 76% reduction in reported dengue cases after the release of mosquitoes infected with Wolbachia bacteria.
However, questions remain about whether the replacement strategy would be effective — and cost-effective — on a global scale, O’Neill says. The three-year Tegucigalpa trial will cost $900,000, or roughly $10 per person, and MSF expects to cover it.
Scientists are not yet sure how Wolbachia prevents transmission of the virus. It’s not clear whether the bacteria will perform equally well against all strains of the virus, or whether some strains may become resistant over time, said Bobby Reiner, a mosquito researcher at the University of Washington.
“It’s definitely not a one-and-done solution, it’s guaranteed forever,” Reiner said.
Special mosquitoes have been bred in Colombia
Many of the Wolbachia-infected mosquitoes were hatched in a warehouse in Medellin, Colombia, where the World Mosquito Program runs a factory that produces 30 million mosquitoes a week.
Edgard Bouquin, one of the leaders of the Honduras project working for Doctors Without Borders, said the factory imports dried mosquito eggs from different parts of the world to ensure that the specially bred mosquitoes it eventually releases will have similar traits to the local population, including resistance to Pesticide.
Place the dried eggs in water with food powder. Once they hatch, they are allowed to reproduce with the “mother colony” – a strain that carries Wolbachia and is made up of more females than males.
A constant noise fills the room as insects mate in cube-shaped cages made of mosquito netting. Caretakers ensure they have the best diet: males get sugar water, while females “bite” bags of human blood kept at 97°F (37°C).
“We have the perfect conditions,” said Marilyn Salazar, plant coordinator.
Once workers confirm that new mosquitoes carry Wolbachia, their eggs are dried and packed into pill-like capsules to be sent to release sites.
Doctors ask for help in Honduras
An MSF team in Honduras recently visited homes in a mountainous neighborhood of Tegucigalpa to ask residents for help in incubating mosquito eggs raised in a Medellin factory.
In six homes, they obtained permission to hang glass jars containing water and a capsule filled with mosquito eggs on tree branches. After about 10 days, the mosquitoes hatch and fly.
On the same day, dozens of young workers from Doctors Without Borders fanned out across northern Tegucigalpa on motorcycles carrying jars of dengue-fighting mosquitoes and, at designated locations, releasing thousands of them into the breeze.
Because community engagement is key to the program’s success, doctors and volunteers have spent the past six months educating neighborhood leaders, including influential gang members, to get their permission to work in areas under their control.
Some of the most frequently asked questions from the community were about whether Wolbachia bacteria would harm people or the environment. The workers explained that any bites from private mosquitoes or their offspring are harmless.
Maria Fernanda Marin, a 19-year-old student, works with MSF in a facility where mosquitoes infected with Wolbachia bacteria are hatched for eventual release. She proudly shows her neighbors a photo of her arm covered in bites to help gain their trust.
Lourdes Betancourt, 63, another MSF volunteer, was initially skeptical about the new strategy. But Betancourt – who has fallen ill with dengue several times – now encourages her neighbors to let the “good mosquitoes” grow in their yards.
“I tell people not to be afraid, that this is not a bad thing, and to have confidence,” Betancourt said. “They will bite you, but you won’t get dengue.”