Wolbachia dramatically reduces dengue cases

The results of a randomised controlled trial published in the New England Journal of Medicine today show that the incidence of dengue was reduced by 77% in areas of Yogyakarta, Indonesia where mosquitoes with Wolbachia were released.

Dengue cases requiring hospitalisation were reduced by 86% in the Wolbachia-treated areas. Efficacy was equivalent for all four serotypes of dengue.

The trial, “Applying Wolbachia to Eliminate Dengue (AWED)”, was conducted by the World Mosquito Program from Monash University with its Indonesia partners Gadjah Mada University and donors the Tahija Foundation. It aimed to test whether the introduction of Wolbachia (wMel) into the local Aedes aegypti mosquito population through the release of Wolbachia-infected mosquitoes would reduce the incidence of virologically-confirmed dengue amongst 3-to-45 year olds living in Yogyakarta, Indonesia.

More than three years after completion of mosquito releases, Wolbachia remains at a very high level in the local mosquito population. Since the trial, the Wolbachia method has been implemented across the entire city of Yogyakarta and releases have commenced into neighbouring districts, to cover a population of 2.5 million people.

The result is consistent with previous trials of the Wolbachia method, which show long-term reduction in dengue incidence once Wolbachia is sustained within the local mosquito population. Dengue is the most rapidly spreading mosquito-borne disease in the world. More than 50 million cases occur globally every year. Studies also show the Wolbachia method to be effective in also preventing the transmission of Zika, chikungunya, yellow fever and other vector-borne diseases. Indonesia is highly endemic for dengue. Recent estimates suggest nearly 8 million cases occur per year.

In the five years prior to the AWED trial, more than 4500 hospitalised dengue patients were notified to the Yogyakarta District Health Office, however this underestimates the true burden of dengueto the healthcare system and society. Economic studies have estimated that there were on average 14,000 dengue cases including 2000 hospitalisations in Yogyakarta each year prior to Wolbachia.

Co-Principal Investigator of the trial, Professor Adi Utarini from the University of Gadjah Mada, said:

“This is a great success for the people of Yogyakarta. Indonesia has more than seven million dengue cases every year. The trial success allows us to expand our work across the entire city of Yogyakarta and into neighbouring urban areas. We think there is a possible future where residents of Indonesian cities can live free of dengue.”

Co-Principal Investigator, Professor Cameron Simmons from Monash University said:

“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.”

World Mosquito Program Director, Professor Scott O’Neill said:

“This is the result we’ve been waiting for. We have evidence our Wolbachia method is safe, sustainable and dramatically reduces incidence of dengue. It gives us great confidence in the positive impact this method will have worldwide when provided to communities at risk of these mosquito-transmitted diseases.”

WMP’s Director of Impact Assessment Dr Katie Anders said:

“There have been very few randomised trials of interventions against the dengue mosquito. These trial results from Yogyakarta show conclusively that Wolbachia works to reduce dengue incidence and dengue hospitalisations. This is consistent with what we have seen from previous non-randomised studies in Indonesia and northern Australia, and with epidemiological modelling predictions of a substantial reduction in dengue disease burden following Wolbachia deployments.”

The AWED Trial's independent statistician, Professor Nicholas Jewell, Professor of Biostatistics and Epidemiology at the London School of Hygiene & Tropical Medicine (and also Professor of the Graduate School at the University of California, Berkeley) said "The results are compelling.  Doubly exciting is that the trial design used here provides a template that other candidate health interventions can follow."

The potential for Wolbachia to be deployed across communities worldwide has been acknowledged by the World Health Organisation, whose Vector Control Advisory Group declared “Wolbachia demonstrates public health value against dengue” in the report of their 14th Meeting in December 2020.