You can kill the messenger – or the viral message. In the second option, the World Mosquito Program found a gift that keeps on giving
Barkha Kumari
If you can’t beat them, infect them.
Scientists got tired of trying to kill off mosquitoes to slow the spread of dengue. So they cut down dengue severity and incidence rate in an Indonesian city by inoculating female Aedes aegypti mosquitoes, the carriers of the disease, with bacteria harmless to them.
The research, led by the World Mosquito Program (WMP), was published in The New England Journal of Medicine last June. The study resulted from a collaboration between WMP, Universitas Gadjah Mada (Indonesia), University of California (United States), London School of Hygiene and Tropical Medicine (United Kingdom), Hospital for Tropical Diseases (Vietnam), and Monash University (Australia).
Female Aedes aegypti mosquitoes are the primary carriers of dengue, which infects up to 400 million humans every year. Their largesse extends to the provision of zika virus (a relative of the dengue virus) and chikungunya. So, researchers grew a batch of these mosquitoes in the lab and infected them with the wMEL strain of Wolbachia – bacteria that thrive in 60% of all insects, such fruit flies, dragonflies, and some mosquitoes, too, but not Aedes aegypti.
What’s so special about wMEL? It can block viral transmission. Thus, when female Aedes aegypti mosquitoes carry the wMEL strain, they are less likely to get infected by the dengue virus and transmit it to humans.
Investigators released the lab-grown, wMEL-carrying mosquitoes in Yogyakarta (Indonesia) to mate with the wild ones and multiply. Now, Yogyakarta has the lowest incidence of dengue in Indonesia – down by 77% in some areas.
Behind the buzz
The wonders of Wolbachia was discovered by Scott O’Neill, Australian professor and head of the World Mosquito Program (WMP), rather serendipitously.
“Aedes aegypti lives for four weeks and transmits dengue in the last week of its life. So Wolbachia could shorten the lifespan of the mosquitoes, it could reduce the dengue transmission, the scientists thought. But they got something even better. Wolbachia blocked the dengue virus from replicating inside Aedes aegypti and infecting it,” Riris Andono Ahmad, co-principal investigator of the latest WMP’s Indonesian team study, told Truly Curious over a Zoom call.
However, this did not come easy as Aedes aegypti is not a natural host for Wolbachia. Researchers had first to extract Wolbachia from fruit flies and inject it into Aedes aegypti eggs to establish a parasitic relationship. It took a few thousand attempts, but they muddled through. Note, that WMP method doesn’t genetically modify the mosquitoes, just prevents them from getting infected.
That was what the UK-based Oxitec has done in Florida, and suffered rich criticism for. That project had aimed to reduce the population of female Aedes aegypti mosquitoes; the WMP method prevents them from getting infected in the first place.
Short-term releases of the Wolbachia mosquitoes in a few areas north of Australia have led to a 93% reduction in reported dengue cases over eight years, the WMP claims here. Notably, the success rate of this mosquito-dependent technology was recently shown in a randomized control experiment carried out by WMP’s Indonesian team.
Testing in the real world
In 2012, the scene shifted to Indonesia, which has one of the highest burdens of dengue in the world, infecting 8 in 10 children. WMP scientists carted Wolbachia-loaded Aedes aegypti eggs over to Yogyakarta, a major dengue hotspot, to hatch, and reproduce with local mosquitoes inside the lab.
Two years later, a team of 100 entomologists, epidemiologists, community engagement specialists and media communicators, had their hands full convincing local authorities and residents that (1) these were good mosquitoes, (2) it was safe to release and let them breed in the open, near houses, and (3) the researchers ought to be allowed to carry out the trial unmolested in four hamlets.
It proved to be a tall task.
“Not only it was a new technology, but it was also counterintuitive,” Ahmad said. “People kill mosquitoes, but we wanted to spread them. So, we had to first educate the regulatory bodies (about its potential), right from the district to the province level. And the public feared that we were messing with Mother Nature.”
So, the team decided to take consent from every available individual to release the mosquitoes in their vicinity.
Though 95% of residents agreed, it still became a point of conflict in the community.
“If a wife agreed, her husband didn’t. If one family was okay, their neighbour wasn’t,” Ahmad recounted with a laugh. “A local activist sent a legal notice to us to not release the mosquitoes in his locality. We were shocked. The news was everywhere.”
Reality bites
The team continued to engage with community leaders, organize dances and games to educate the masses, and send bike campaigns in tiny lanes and paint murals around the city.
“Community support was essential. The only way to prove that the technology worked or not was to take it out in the public,” Ahmad talks about his biggest takeaway from the project.
Their persistence paid off, and they were able to deploy the good mosquitoes at a small scale. “In Phase 2, we wanted to test if Wolbachia could establish itself in the naturally-occurring mosquito population by mating and growing,” Ahmad explains. It did.
In 2016, they identified an area with a high-density population in Yogyakarta and divided it into two parts – 12 ‘intervention clusters’ where they would release the good mosquitoes and 12 ‘control clusters’ where they wouldn’t. The following year, they enrolled 8,144 participants aged 3-45 years old and monitored their health in these clusters. Unfortunately, they had to wrap up the trial in March 2020 because of the pandemic.
Researchers found that 2.3% of participants reported virologically-confirmed dengue (VCD) in the areas with good mosquitoes, while that number was 9.4% in the areas without them. The incidence of hospitalisation was also lower in the intervention areas than in the control ones – 0.4% against 3%.
Overall, the study concluded that the protective efficacy of the ‘Applying Wolbachia to Eliminate Dengue’ trial is 77.1% against all four strains of the dengue virus.
What explains the 23% failure? “Daytime is when the dengue mosquitoes bite, and it’s also the time when people criss-cross through the city. So, they may have caught dengue from non-intervention areas,” Ahmad shares and takes us back 20 years to explain how far Yogyakarta has come. “I was interning at a medical school in Yogyakarta when a dengue outbreak occurred. Hospital rooms were packed. We had to accommodate patients in the corridor. The situation was a bit like COVID-19. But since 2019, Yogyakarta is reporting the lowest cases of dengue.”
Interest check
So is Yogyakarta or, for that matter, Indonesia open to more good mosquitoes in their backyards? So far, the Wolbachia-carrying Aedes Aegypti have been released in only two other districts, Sleman and Bantul. “The ministry of health has expressed interest, but they want to approach it systematically,” he informs about the slow uptake. He doesn’t know whether other countries have reached out to WMP to execute this dengue control in their environs.
Last year, the Vector Control Advisory Group of WHO recognised the public health importance of WMP’s Wolbachia-led dengue control. It also predicted that the chances of Wolbachia developing resistance against the dengue virus are low.
The WMP method’s has immense potential to control mosquito-borne diseases, given that lab studies suggest Wolbachia infections can slow the transmission of Zika, chikungunya, yellow fever, and Mayaro viruses. It is pretty cost-effective, given the enormous budgets set aside for insecticides every year.
The biggest advantage in this treatment, says Ahmad, is that “once Wolbachia establishes itself in a mosquito population, it passes down from generation to generation.”
That is one way to make a mosquito lose its bite.
Barkha Kumari is a freelance journalist based in Bengaluru, India. You can follow her on Barkha2803
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