JAKARTA – Overshadowed by government efforts to develop a coronavirus vaccine, Indonesian researchers have quietly played a key role in a major breakthrough that could lead to the elimination of dengue fever, the mosquito-borne scourge whose symptoms Covid-19 often mimics.
An initial trial by the Australian-based Monash University’s World Mosquito Program (WMP) has shown a stunning 77% reduction in the incidence of dengue in parts of Jogjakarta where mosquitos were released carrying Wolbachia, a tiny bacterium which occurs naturally in 60% of insect species.
When Wolbachia is introduced, it boosts the mosquito’s natural immune system and also consumes key molecules, like cholesterol, making it much more difficult for viruses to grow.
Over time, the treated insects breed with female Aedes Aegypti mosquitos, increasing the percentage of those with Wolbachia to a point where it becomes a self-sustaining way of blocking the transmission of dengue and other viruses like zika, chikungunya and yellow fever.
Working with the philanthropic Tahija Foundation and Jogjakarta’s prestigious Gadja Mahda University, the WMP chose 24 same-sized clusters covering a 26 square-kilometer area of Jogjakarta; 12 were selected at random for the trial and the other 12 remained untreated.
In the end, the three-year program involved 8,144 participants, aged three to 45, who were recruited to take part in the study when they reported to primary care clinics with acute fever.
“For us, this will bring new hope to better control dengue,” says Dr Adi Utarini, a British-trained public health researcher at Gadja Mahda University who co-led the trial. “We are particularly curious now if the government has the enthusiasm to scale up the program.”
“It’s going to have a huge impact,” says Professor Cameron Simmons, principal investigator and WMP Oceania director, calling the study a “gold standard” in what it has achieved. “We have never got to use the words ‘dengue’ and ‘elimination’ together at one time.”
Simmons says Wolbachia-carrying mosquitoes have now reached more than five million people in 12 countries where WMP is now active, mostly in Brazil (Rio de Janeiro) and Colombia (Medellin), but also in Sri Lanka and Vietnam.
Vector control, through chemical or biologic targeting of mosquitoes and the removal of their breeding sites, has been the mainstay of the program so far, but this approach has failed to stop transmission in most countries where the disease is endemic.
Nicholas Jewell, a biostatistician at the London School of Hygiene and Tropical Medicine who offered his services as a pro bono consultant, says the 77% reduction translates to people being four times less likely to develop the disease.
“I’ve never been involved in a study quite as successful as this,” Jewell told the British scientific journal Nature. “We’ve never had anything like this. Condoms provide this level of protection.”
Two years after the last mosquito releases, Wolbachia is persisting at a high rate in the mosquito population of Jogjakarta, a cultural and education center in Central Java where the disease is endemic.
The results of the study are to be presented to the American Society of Tropical Medicine and Hygiene’s virtual annual meeting in November, prior to the WMP making an application for formal approval from the World Health Organization (WHO).
Asked if he thought the coronavirus pandemic would overshadow the dengue breakthrough at the conference, Simmons told Asia Times: “We will be happy to be a ray of good hope.”
The Aedes Aegpyi mosquito originated in Africa and spread to tropical and subtropical regions around the world at the height of the slave trade in the 18th and 19th centuries, and then again following troop movements during World War II.
The Tahija Foundation decided not to invite the direct participation of the Bill Gates Foundation, which funds much of the worldwide fight against malaria. “Gates is so huge, we decided we would do it alone,” says chairman Syakon Tahija, a leading retina specialist.
The billionaire’s foundation did however absorb the costs of mathematical and other studies where the Jogjakarta trial intersected with wider mosquito control programs.
Indonesia has an estimated eight million cases of dengue each year, reflecting a thirty-fold increase in global incidence over the past 50 years. The vast majority go unreported, but hundreds of mostly children and elderly people die each year.
Although one is spread by mosquitos and the other by human contact, Indonesia’s Health Ministry reported last June that 400 cities and districts across the country have recorded cases of double infection, where dengue and Covid-19 have occurred together in one patient.
China’s Sinovac Biotech Ltd and state-owned Bio Farma have recently launched late-stage human trials of a coronavirus vaccine, and the respected Eijkman Institute for Molecular Biology is working on the home-grown Merah Putih vaccine, named after the colors of the national flag.
The medical community remains skeptical about the veracity of the Sinovac vaccine, but the government recently signed a deal with the Chinese firm to deliver up to 40 million doses in November. “They’re grabbing at whatever they can,” says one doctor. “The government feels cornered.”
The WMP’s program is one small example of what it takes to come up with a lasting cure for a dangerous disease, in this case one that its worst form can develop into life-threatening haemorrhagic fever.
In fact, the program goes back to the 1990s when microbiologist Scott O’Neill and his Monash team successfully bred laboratory populations of Wolbachi-infected mosquitos that showed promising results in early uncontrolled field studies in northern Australia.
But starting in 2011, it took years for the partners to go through a wide spectrum of safety requirements in Indonesia, including proof that only local mosquitoes were being deployed and also that those carrying Wolbachia were staying in one place.
Interestingly, researchers say the trial showed that as much as they propagate, mosquitos don’t wander far from their original habitat. In fact, they have a proven reluctance to cross natural barriers such as rivers and paddy fields.
Adi says now the method is known to be effective, the next step will be to release the modified mosquito in the rest of the city. That means depositing buckets of eggs every 50 meters in different areas over the next five months, with the goal of spreading Wolbachia to 80% of the mosquito population.
Early next year, the WMP and its partners will turn their attention to Sleman and Bantul, two outlying districts of the wider Jogjakarta Special Zone where dengue remains endemic. But beyond that, the government will have to take the leading role.
Tahija hopes the Health Ministry will quickly adopt the Wolbachia method for further trials in Jakarta, Bandung, Surabaya, Bali and other known breeding grounds. As he puts it: “If you can get rid of dengue over time, you’ve got one less health problem to deal with.”
Because health is decentralized, Adi believes the leap from one city to the entire nation is too big. Rather, she says, it would be better for programs to be initiated by district governments where the dengue problem is particularly acute.
That will mean going through the same process in each new trial area, all dependent on such factors as the vagaries of the climate, local politics, the openness of local administrations and a public willingness to accept new ideas. Like dealing with Covid, he says, nothing will be easy.