A ‘Breakthrough’ Trial Used Bacteria-Infected Mosquitoes to Stamp Out Dengue

A ‘Breakthrough’ Trial Used Bacteria-Infected Mosquitoes to Stamp Out Dengue
A photo of Aedes aegypti mosquitoes infected with the Wolbachia bacterium, taken at the Oswaldo Cruz foundation in Rio de Janeiro, Brazil, on October 2, 2014. (Photo: Christophe Simon/AFP, Getty Images)

An unconventional ploy to combat dengue in Indonesia seems to have gone incredibly well.

In a new study published this week, scientists report that cases of dengue, a deadly mosquitoborne illness, dramatically shrunk in areas where they introduced mosquitoes intentionally infected with a bacteria called Wolbachia. The bacteria are thought to prevent the mosquitoes from catching dengue in the first place. These results are the strongest evidence yet that Wolbachia can help eradicate dengue and other nasty infections spread by mosquitoes.

Over the past few decades, dengue has become one of the most common infections in the world. Also known as breakbone fever for the debilitating pain it can cause, the viral illness is estimated to infect up to 400 million people worldwide and sicken 100 million people annually. It can also rarely turn into a life-threatening infection that causes severe internal bleeding, known as hemorrhagic fever.

The toll of dengue has long made it an appealing target for research. In 2016, the first-ever dengue vaccine was approved, called Dengvaxia. But the vaccine is only moderately effective and is not recommended for people who have never had dengue before, since it can raise the risk of severe illness if the person encounters dengue for the first time post-vaccine (for people who’ve already had dengue, the vaccine helps prevent subsequent infections from becoming serious). So there’s still a need for better anti-dengue measures.

In recent years, some scientists have been working on another strategy, cribbed from nature itself. Many insects often carry Wolbachia, bacteria that need to live inside cells to survive. Wolbachia’s interactions with its hosts can be incredibly complex and often symbiotic, to the point where the insects rely on them for survival. Some mosquitoes, particularly Aedes aegypti, the main vector of dengue, don’t usually carry Wolbachia. But when they do, the bacteria makes infected male mosquitoes incapable of successfully reproducing with uninfected female mosquitoes; at the same time, the infection gets passed down to offspring. This knowledge has led to scientists creating a technique where infected male mosquito eggs are dropped into an area, mature into adults, and then try, unsuccessfully, to breed with the local females, eventually leading to the population’s decline.

Other groups have been testing out a slightly different approach. Their research has shown that when you infect Ae. aegypti mosquitoes with a specific Wolbachia strain, one lifted from fruit flies, they become much less capable of catching and transmitting dengue. These mosquitoes also spread Wolbachia to the next generation, ensuring that the bacteria keeps working as a dengue deterrent, without needing to go through the long process of trying to wipe out the local mosquito population.

Studies of this method have been ongoing since 2011, including in parts of the U.S., led by the World Mosquito Program (WMP). These studies have suggested that the strategy could be successful without causing any negative impacts to people or wildlife. But the group’s latest study, a three-year randomised controlled trial published in the New England Journal of Medicine on Wednesday, is their largest test of it yet, and it looks to have passed with flying colours.

The study involved around 8,000 residents living in Yogyakarta, Indonesia, where dengue is endemic. Their neighbourhoods were divided into 24 clusters, and the team’s infected mosquito eggs were deployed in half of these areas, while the native skeeter population was left alone in the other half. In areas where the infected mosquitoes were planted, cases of confirmed dengue infection dropped by 77% over the study period, compared to control neighbourhoods. Dengue-related hospitalisation also dropped by 86% in the experimental areas.

“This trial result shows the significant impact the Wolbachia method can have in reducing dengue in urban populations. 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,” said co-lead author Cameron Simmons from Monash University in a statement from the WMP.

The results from this kind of clinical trial, often seen as the gold standard in proving a treatment works, are likely to lead to much greater acceptance of its use. The WMP has already pledged to treat the rest of Yogyakarta, and they hope to expand their project to reach areas covering as many as half a billion people at risk for dengue within the next decade, with approval from governments and residents, Nature News reported last year. In the best-case scenario, this technique coupled with others could someday lead to the eradication of dengue altogether, as well as other mosquitoborne viruses like Zika and chikungunya.