Scientists just got a step closer to eliminating the spread of mosquito-borne viruses, with an experimental approach against dengue fever passing its most thorough test yet.
In a randomized, double-blind trial, researchers introduced mosquitoes infected with the virus-fighting Wolbachia bacteria into an Indonesian city. Over the next 27 months, the participants in the areas with the bacteria-carrying insects experienced 77 percent less dengue than those in the control group.
"This result demonstrates what an exciting breakthrough Wolbachia can be - a safe, durable and efficacious new product class for dengue control is just what the global community needs," says infectious researcher Cameron Simmons from Monash University. He's also director of the Oceania Hub at the World Mosquito Program, which led the trial.
Dengue fever, caused by the dengue virus, is spread by female Aedes aegypti mosquitoes. It's found globally in tropical and sub-tropical areas and in recent decades infections have surged, with an estimated 100 to 400 million infections each year. The World Health Organization now considers dengue the most critical mosquito-borne virus in the world (malaria is caused by a parasite, not a virus).
Dengue fever often presents with flu-like symptoms but in rare cases it can also trigger severe dengue, which is associated with bleeding, organ failure and risk of death. Up to 25,000 people die from the disease each year.
There's currently no commonly accepted treatment, and the vaccine is only recommended for those who have already been infected with the dengue virus, as the inoculation can trigger severe dengue in those who've never had the disease.
The good news is that in recent years, an experimental approach has shown promise in slowing down the disease's spread: the introduction of a bacterium called Wolbachia into mosquito populations.
Wolbachia is naturally found in around 60 percent of insect species, and when introduced to A. aegypti, it's passed from generation to generation, which means eventually all mosquitoes in a population will be infected with Wolbachia.
Bacterial infection may sound like a bad thing, but research has shown that when the mosquitoes carry the bacteria, it slows down the reproduction of viruses, making it less likely they'll be transmitted to other people. Excitingly, while dengue is the focus of this work, Wolbachia has also been shown to work against yellow fever, Zika virus and chikungunya.
Scientists have been actively infecting A. aegypti mosquitoes with Wolbachia and releasing them for more than a decade in various test sites including Brazil and Fiji, and extensive research has shown that the approach poses negligible health risks for humans and the environment.
Already in Australia's far north Queensland, dengue has been basically eradicated thanks to the World Mosquito Program's Wolbachia trial.
However, it can be hard to set up adequate trial parameters when working with real-world populations, and the latest approach is one of the first randomized trials. It's also the first to measure for virologically confirmed dengue, making it the most thorough test to date.
"I really think the results of this trial will be a game changer," says World Mosquito Program Director of Impact Assessment, Katie Anders.
"There have been a lot of people watching our work over the years – waiting to see the results of this trial. Now that they're published people don't need to take our word for it. The data is there that this really works to prevent dengue."
Working with the local community in a 26 km2 (10 square mile) area of Yogyakarta city in Indonesia, the researchers divided the region into 24 geographic clusters.
Between March and December 2017, the team randomly deployed Wolbachia-infected mosquitoes in 12 of these clusters (known as the intervention clusters). The other 12 clusters received no deployments and were used as controls. All clusters in the study continued to practice local mosquito-control measures throughout the trial.
The researchers then recruited people aged between 3 and 45 who presented at primary care clinics with any kind of undifferentiated fever over the next 27 months. They used lab tests to identify which of these had dengue and which didn't.
Over the trial, they tested a total of 8,144 participants. The lab results showed that only 67 people (or 2.3 percent) in the intervention clusters where Wolbachia-carrying mosquitoes had been introduced had clinically diagnosed dengue fever, compared to 9.4 percent of people (318 cases) in the control clusters.
Overall, the introduction of the bacteria-carrying mosquitoes reduced the spread of dengue by 77.1 percent. This result was similar against all four dengue fever subtypes.
The study also found that 86 percent fewer people who lived in intervention clusters ended up in hospital as a result of fever: 13 hospitalizations compared to 102 in the control areas
"This is a great success for the people of Yogyakarta," says team member Adi Utarini from the World Mosquito Program and the University of Gadjah Mada in Yogyakarta, Indonesia.
"For a long time, people have always gone into sporadic panic, especially every rainy season," she adds. "Worse still, this disease mostly strikes children, making the death rate among children relatively high."
In far north Queensland, Australia, it only took four years for no dengue transmissions to be recorded following the release of Wolbachia mosquitoes in the Cairns region; however, it's worth noting the disease was never endemic there.
Hopefully with these positive results, it will only be a matter of time before we see similar results in other regions of the world still battling this disease.
The research has been published in the New England Journal of Medicine.