Q&A: Mosquito breeding trial raises hopes of defeating dengue

MANILA — Public health messaging for dengue control often encourages the clean-up of mosquito breeding sites. But a novel method that researchers at the World Mosquito Program have introduced to several communities over the past eight years directly counters that concept.

Instead of killing mosquitoes, they breed mosquitoes injected with Wolbachia bacteria and release them to communities that have been affected by dengue.

Evidence from different countries where the method has been used showed large reductions in dengue transmissions. There was a 96% reduction in cases of dengue transmission in Australia’s Far North Queensland region, where Wolbachia-infected mosquitoes were released in 2011. In Yogyakarta, Indonesia, where Wolbachia-injected mosquitoes were released in 2016, researchers found a 76% reduction in dengue cases.

But the method is not just having an impact on communities suffering from dengue. In the city of Niterói in Brazil, the Ministry of Health found a 75% reduction in cases of chikungunya in 2018-2019 when compared in areas where the method was not introduced, as reported by the program’s researchers at last week’s Annual Meeting of the American Society of Tropical Medicine and Hygiene.

“We have strong evidence that it impacts the Zika virus,” Cameron Simmons, director of impact assessment and an expert in the epidemiology of dengue at the World Mosquito Program, told Devex.

Simmons said the method is for diseases transmitted by the Aedes aegypti mosquito, which also carries yellow fever. But if the technology is so effective, why hasn’t it been used widely? Devex asked Simmons.

The conversation has been edited for length and clarity.

If the method has been used for years, what’s new in what you’re presenting?

The work started in North Queensland in 2011, and it has expanded to 12 countries now, in Asia, Western Pacific, and Latin America.

What’s new is the growing evidence, that this method of releasing Wolbachia mosquitoes and establishing Wolbachia in communities that have been affected by dengue, substantially reduces the incidence of dengue. We also have some evidence that it reduces the incidence of chikungunya and other diseases transmitted by the Aedes aegypti mosquito. So really what we’re showing now is what years of laboratory and modeling work suggested would happen, and that is Wolbachia reduces disease risk in communities that otherwise are routinely hit by dengue outbreaks.

Why hasn’t it been used as widely to date?

The method is not about suppressing the mosquito population, but about transforming them to a population that carries Wolbachia. So it’s novel.

It started as a research, so it takes time to work with countries and country partners, and for countries to do risk assessment to run the technology. That’s a time-consuming process. But what we’re seeing now, as public health evidence grows, there’s much greater appetite from these affected countries to try this technology in their own backyards.

Evidence shows huge reductions in cases. But why not 100%?

I think it’s the nature of the study. It’s impossible to get to 100% unless you blanket a whole city.

The size of the communities we’re working in, people move in and out of their community. When they move out, usually they move away from this umbrella protection that Wolbachia provides. So just the nature of those studies means that it’s probably impossible to get to 100% because of human mobility. But if we look at [the intervention in] Australia, [it’s] near elimination.

Can you briefly explain the process of releasing the mosquitoes? You grow the mosquitoes, inject them with Wolbachia in the lab, and then when do you decide to release them?

We work together with governments and communities, so we’re only releasing it to a community when the government has said it’s OK to do so, and when the communities say it’s OK to do so.

That’s very important. This is not a top-down intervention. We always work with communities to make sure they’re comfortable with what we’re doing. And then we essentially factory farm these mosquitoes, and then release these mosquitoes in the community in the form of adult mosquitoes, or in the form of mosquito eggs and let them grow in the community so to speak.

And release typically takes between 10 to 20 weeks to occur, and then critically Wolbachia stays in the mosquito population … for years and probably decades, without us ever having to do a reapplication.

So it’s a sustainable intervention, and what the evidence suggests so far is that public health benefit is sustained also for years and probably decades.

Why is it important to do community outreach and education first?

What we’re doing by releasing mosquitoes is really quite counter to what public health messaging is currently around disease control. For decades public health messaging has been about cleaning up your environment, stop mosquitoes from breeding, to kill mosquitoes, all to reduce dengue risk.

And here we are, coming along with a solution to stop dengue, but we’re releasing mosquitoes. So we need to communicate to the community why we’re releasing mosquitoes, explaining how Wolbachia works and making sure they’re comfortable and happy with the approach.

And by and large, when we do that communications and community engagement well, communities are very enthusiastic about our approach.

Are there particular conditions that a community should meet for this method to be used?

Not really. The intervention is most cost-effective in communities where there’s a high population density — because the cost of deploying the mosquito we calculate on a per-kilometer basis. So if it’s 10,000 people living in a square kilometer, it’s highly effective for us to deploy our mosquitoes compared to for example a rural community with a small population.

So there’s no way where the technology couldn’t work. It’s just that there are higher priority locations in endemic countries.

Everything sounds so positive. But is there anything negative that could happen in the environment?

We let countries do their own independent risk assessment. Indonesia, Vietnam, Australia, Brazil have all done independent risk assessments to look at … the possible risks of this method versus the positive outcomes from a public health sense. And so that’s a balancing act, and in that risk assessment process, countries have decided that there are negligible risks with this method, based on all the science we know about Wolbachia. But that the possible positive public health outcomes are such that it’s the method that deserves to be tried.

We can certainly lookout for any safety concerns, [but] we’ve not found any so far. We let independent experts look at the technology, and decide whether it fits the purpose in their own countries.

You mentioned you’re hoping to bring this method to 100 million by 2023. What will it take for you to get there?

We need to be able to scale as an organization and to work with a range of partners across the world to deploy the mosquitoes. We certainly can’t do that ourselves. So we need to work through partnerships to achieve that sort of scale.

We need to get better at making mosquitoes … We need to be quite sophisticated producers of those mosquitoes, so we can support the demand that we think is there. And of course, we need funding to be able to do it. That funding may come from governments, city and municipality governments, and it may come from large philanthropy. We’ve been very fortunate to be funded by the Bill & Melinda Gates Foundation and the Wellcome Trust for a number of years.`

How much does it cost now?

At the moment, it’s somewhere between $2 to $10 per person protected. What we’re trying to do is to get that to less than $1 per person protected, and even better less than 50 cents per person protected. And remember that’s a one-off cost. It’s not a recurring cost.

And as we scale and get more efficient at our mosquito deployment, that price would come down.

Is it currently recommended by WHO in vector control interventions?

We were endorsed by WHO during the Zika virus public health emergency in 2016 as a method that governments could pilot because of the evidence associated with what we’re doing at that point.

So we are looking forward to having this in the next 1-2 years additionally endorsed by WHO. And I think an important inflection point for us will be the results from a large phase 3 clinical trial that’s being conducted in the city of Yogyakarta in Indonesia. That’s due to deliver next year.

The WHO is an important stakeholder. Endorsement from WHO would provide that confidence to ministries of health that this is something that should be part of their programs of disease control, and therefore worthy of taxpayers’ money.