A 27-month study in Indonesia of a unique mosquito control method shows that the strategy can reduce the incidence of dengue fever – a mosquito-borne viral disease in the tropics that threatens nearly half the world’s population – by 77%.
The method that uses Aedes aegypti mosquitoes infected with a bacteria called Wolbachia is effective in preventing mosquitoes infected with dengue from transmitting the virus when they bite people. The study, the preliminary results of which were released today (Wednesday, Aug. 26), only looked at dengue, but the mosquito control strategy could likely work for other viruses transmitted by A. aegypti mosquitoes, including Zika , Chikungunya and yellow fever.
“It’s a major breakthrough,” said Nicholas Jewell, professor at the University of California Graduate School at Berkeley who designed the study and led the statistical analysis. “We have now shown that it works in a city. If this can be replicated and spread widely, it could eradicate dengue fever from several parts of the world for years to come. “
More than two years after the mosquito release in the city of Yogyakarta on the island of Java, Wolbachia remains at a very high level in the local mosquito population, the researchers found.
“This exciting outcome of the process is a great achievement for the people of Yogyakarta,” said Adi Utarini of Gadjah Mada University in Indonesia, co-principal investigator of the process. “Indonesia has 7 million cases of dengue every year. This test result shows the significant influence the Wolbachia method can have on the reduction of dengue fever in urban population groups. “
Dengue fever is growing rapidly worldwide – in part due to global warming – creating a public health challenge and economic burden. It is estimated that 50 million cases occur worldwide each year. However, there is currently no effective vaccine to prevent this, as the one approved vaccine has only limited efficacy and requires considerable care when administered to children. There is also no therapeutic agent to treat dengue fever and no effective vector control strategy to prevent its spread. In 2019, the World Health Organization declared dengue to be one of the top ten health threats worldwide due to the lack of effective interventions.
While mild symptoms include fever, lethargy, headache, eye pain, nausea, and rash, severe cases can include severe abdominal pain, persistent vomiting, rapid breathing, signs of bleeding, and vascular leakage. Life-threatening complications are dengue shock syndrome and / or severe organ dysfunction.
Dengue and Zika are even invading the US as global warming encourages the A. aegypti mosquito to move north from the Caribbean, bringing with it the diseases that go with it. Florida had small dengue outbreaks while A. aegypti was found in California’s Central Valley. As soon as a traveler brings dengue fever, yellow fever, zika or chikungunya to the US and is bitten by one of these mosquitoes, the disease can become endemic.
“This is how Zika spread around the world,” Jewell said, referring to recent outbreaks, including those in South America in 2015 and 2016, which caused birth defects in the children of many pregnant women who were infected. “People got it after they traveled, and then the local mosquito population got Zika, and then other people got Zika and off we go. This is exactly how mosquito-borne diseases work. “
It is precisely at such hotspots in Australia that a group from Monash University, the World Mosquito Program (WMP), first piloted their extermination strategy and reported very encouraging results last year that made headlines around the world.
The Indonesian study is the first controlled study of the strategy in which the WMP worked with the Tahija Foundation and Gadjah Mada University.
The researchers divided the city of Yogyakarta – about the size of the city of Berkeley, but with almost four times the population – into a chessboard of 24 clusters and randomly released Wolbachia-infected mosquitoes in half. They then worked with all of the city’s medical clinics to identify patients with acute fever and determine which clusters they had lived or visited in the previous 10 days. All patients were then tested for dengue, which is usually not done because the results come back too late to affect treatment.
“It was a complicated study,” said Jewell. “It wasn’t like a vaccine trial where you could accidentally get people to get a vaccine or not. This is not possible with mosquito-borne diseases. You need to do this across geographic areas and watch out for the mosquitoes to drift away as we used a random checkerboard pattern of the areas in this major city. “
The study area included approximately 312,000 people, and the researchers found that the Wolbachia outreaches were well received by the community with no safety concerns. A total of 8,144 people aged 3 to 45 years after acute undifferentiated fever between one and four days took part.
Jewell and PhD student Suzanne Dufault who completed their UC Berkeley Ph.D. last spring received the blinded data in June and analyzed it within a week.
“It was an extraordinary result. The 77% reduction in dengue incidence is enormous by pharmaceutical intervention standards, ”said Jewell. “We’re going to deal with the rest of the city now – that was part of the deal, if it worked. I think we will then have a chance to eradicate dengue fever in Yogyakarta. “
This trial is the culmination of a decade of laboratory and field studies that began first in Australia and then expanded to 11 dengue endemic countries.
“We have been waiting for this result. We have evidence that our Wolbachia method is safe, sustainable and reduces the incidence of dengue, ”said WMP Director Scott O’Neill of Monash University. “Now we can scale this intervention across cities. It gives us great confidence in how we can extend this work to large urban populations around the world. “
A major advantage of this strategy is that the mosquitoes infected with Wolbachia only have to be released once and the Wolbachia infect a large part of the mosquito population. This does not reduce the mosquito population, as some control measures do, since the mosquitoes reproduce essentially normally. However, because mosquitoes do not travel far in their short lifespan, they must be bred and released in many places to cover large areas.
Nevertheless, the method is the first effective intervention for such deadly diseases.
“The basic story is, you put the bacteria in the mosquito, you breed the mosquito, you put it in, it blocks the virus and bingo,” said Jewell, who is also a professor of biostatistics and epidemiology at the London School of Hygiene is tropical medicine. “It not only blocks one virus, it also blocks many flaviviruses. It’s like a miracle cure. But would it work? Here we have finally shown that it works in practice. “