June 2021
- Trial results published in The New England Journal of Medicine show 77% reduction in dengue incidence in Yogyakarta, Indonesia
- Dengue hospitalisations reduced by 86%
- Result has significant implications for 40% of the world’s population at risk of dengue
- World Health Organisation’s Vector Control Advisory Group recognises “public health value of Wolbachia against dengue"
The results of a randomised controlled trial published in the New England Journal of Medicine 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.[1]
Dengue is the most rapidly spreading mosquito-borne disease in the world.
More than 50 million cases occur globally every year[2].
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[3].
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 dengue to 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.[4]
Co-Principal Investigator of the trial, Prof. Adi Utarini from the University of Gadjah Mada, said
“This is a great success for the people of Yogyakarta. Indonesia has more than 7 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, Prof. 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, Prof. 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, Prof. 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 13th Meeting in December 2020.[5]
World Mosquito Program Monash University Media contact:
Dale Amtsberg E dale.amtsberg@worldmosquito.org | T +61 437 873 071
About the “Applying Wolbachia to Eliminate Dengue” trial in Yogyakarta, Indonesia
Twelve of twenty-four similarly-sized and predefined areas of Yogyakarta city were chosen at random to receive wMel Wolbachia-deployments in addition to routine dengue control measures; the remaining 12 continued to receive routine dengue control efforts. The trial area had a total population of ~312,000 people[6].
The trial enrolled 8,144 participants aged 3 to 45yrs who presented to one of 18 primary care clinics with acute undifferentiated fever of between 1 to 4 days duration. A case test-negative design was used to measure the efficacy of wMel in reducing the incidence of virologically-confirmed dengue cases over a 27-month period. Wolbachia deployments were well-accepted by the community and there have been no safety concerns.
This trial is the culmination of a decade of laboratory and field studies, beginning first in Australia and then expanding to 11 dengue endemic countries.
Quotes from Local Indonesian Partners
Dr Yudiria Amelia
Head of Disease Prevention & Control Division. Health Agency, Yogyakarta City
“Yogyakarta city is an endemic dengue area. For us, Wolbachia is the right method to be integrated with the existing dengue control program. We are delighted with the outcome of this trial. We hope this method can be implemented in all areas of Yogyakarta and further expanded in all cities in Indonesia.”
Mrs Riyan
local Yogyakarta community member
Head of Community Reference Group for AWED trial
“The community has so much hope and expectation for the success of this research. That is why we are so positive. We have welcomed this project to our community.”
Dr Sjakon Tahija
Chairman of the Tahija Foundation
“As the funder for this Wolbachia program, we would like to thank all partners and stakeholders for this multi-year, excellent collaboration that has had such an impact reducing the burden of dengue in Yogyakarta, and globally in the near future. As a venture philanthropy foundation, we are proud that our investment will surely bring sustainable impact. We are very excited and proud of this result.”
About dengue
Dengue is a self-limited, systemic infection caused by any of the four serotypes of dengue virus. Dengue viruses are transmitted between humans primarily by Aedes aegypti mosquitoes. These mosquitoes also spread the Zika virus and chikungunya virus.
Dengue is endemic throughout the tropics where it is a threat to nearly half the world’s population. The rapidly expanding global footprint of dengue is a public health challenge and an economic burden that is currently unmet by effective vaccines, specific therapeutic agents, or efficient vector-control strategies [7]. In 2019 the World Health Organisation declared it one of the top ten global health threats because of the absence of effective interventions.
The clinical manifestations of dengue occur on a spectrum of severity. Mild cases typically experience fever, lethargy, headache, retro-orbital pain, nausea and rash for 5-7 days. More severe cases may present with one or more of; severe abdominal pain, persistent vomiting, rapid breathing, signs of bleeding and vascular leakage. Life threatening complications include dengue shock syndrome and/or severe organ dysfunction. Severe dengue is a leading cause of serious illness in some tropical countries and requires intensive care by experienced medical professionals[8].
Vector control, through chemical or biologic targeting of mosquitoes and removal of their breeding sites, is the mainstay of dengue prevention, but this approach has failed to stop disease transmission in almost all countries where dengue is endemic
About the self-sustaining Wolbachia method
The Wolbachia method works by introducing Wolbachia into Aedes aegypti mosquitoes that transmit the dengue, chikungunya, Zika and yellow fever viruses. These Wolbachia carrying mosquitoes are released in areas where mosquito-borne viruses are endemic. Once Wolbachia carrying mosquitoes are released, they breed with wild mosquitoes. Over time, the percentage of mosquitoes carrying Wolbachia grows until it remains high without the need for further releases. This self-sustaining method offers a safe, effective, and long-term solution to reducing the burden of these diseases.
The World Mosquito Program has committed to transferring the knowledge and tools required to produce and release Wolbachia-carrying mosquitoes at scale to all dengue-affected countries. Our goal is to help catalyze the rapid scale up of this unique dengue protection method over the next decade. WMP aims to work in partnership with national and local governments, corporate citizenship programs, charitable organizations and non-governmental organizations to expand Wolbachia protection worldwide. To date, WMP has supported releases in 11 countries in Asia, Australia, Latin America & the Pacific. An estimated 6.8 Million people now benefit from Wolbachia coverage.
About the World Mosquito Program
Working to help protect the global community from mosquito-borne diseases, the World Mosquito Program, formerly the Eliminate Dengue Program, is a not-for-profit initiative led by Prof Scott O’Neill at Monash University, Australia. It uses a safe, natural, and effective method to reduce the threat of viruses such as Zika, dengue, chikungunya and yellow fever. Through our collaborative and innovative approach, we are helping to protect local communities from these diseases in Australia, Asia, Latin America, and the Pacific Islands. Following many years of laboratory research and field trials with promising results, the World Mosquito Program is now operating in 11 countries around the world.
About University of Gadja Mada
Universitas Gadjah Mada is an Indonesian public ivy league research university located in Yogyakarta, Indonesia, founded on December 19, 1949. UGM is the oldest and largest institution of higher learning in Indonesia. Located in Yogyakarta, Indonesia, the 360-acre university comprises 18 faculties, 68 undergraduate study programs, 23 diploma study programs, 104 master and specialist study program, and 43 Doctorate study programs.
About Monash University
For more than 60 years, we’ve been working hard to change the world. Every project we support is driven by a desire to make a difference.
We're tackling climate change, developing new drugs to save millions of lives, using virtual reality to treat addiction, bringing sight to the visually impaired, and so much more.
Our work improves health, solves complex global challenges and empowers whole communities.
We're working every day to create real, lasting global change and we encourage and challenge our students to be at the forefront of innovating for a better future. Combining world-leading teaching, research, facilities and experiences, Monash University ranks in the world’s top 100 universities.
Find out more: monash.edu/research
About the Tahija Foundation
The Tahija Foundation is a non-profit organization established in Jakarta by the late Mrs. Jean Tahija and Mr. Julius Tahija on March 21, 1990. The Tahija Foundation is a formal vehicle for the philanthropic initiatives of the Tahija family.
It seeks to bring about a better Indonesia through partnership for sustainable initiatives in education, culture, health, environmental conservation and social services.
World Mosquito Program Monash University Media contact:
Dale Amtsberg E dale.amtsberg@worldmosquito.org | T +61 437 873 071
[1]Peter A Ryan et al., September 2019, Gates Open Research https://www.worldmosquitoprogram.org/en/learn/scientific-publications/establishment-wmel-wolbachia-aedes-aegypti-mosquitoes-and
[2] Global Burden of Disease study, 2019
[3] O’Reilly KM, Hendrickx E, Kharisma DD, et al. BMC Medicine. 2019;17:172
[4] Brady OJ, Kharisma DD, Wilstonegoro NN, et al BMC Medicine. 2020;18:186
[5] https://www.who.int/vector-control/vcag/meeting-reports/en/
[6] Anders KL, Indriani C, Ahmad RA, et al. Trials. 2018;19:302
[7] Simmons CP, Farrar JJ, Nguyen VVC, et al. Dengue. N Engl J Med. 2012;366:1423-1432
[8] Wilder-Smith A, Ooi EE, Horstick O, Wills B. Dengue. Lancet. 2019;393(10169):350-363.
