World Mosquito Program: innovating disease control

As spring arrives here in the United States, we’re enjoying longer days as the world around us blooms. But then we are reminded with that first buzz in our ear that warming weather brings mosquitoes.

We sat down this month with Scott O’Neill, an internationally recognized scientist and founder of the World Mosquito Program, to learn all about mosquitoes. The World Mosquito Program is a grantee partner of both the Bill & Melinda Gates Foundation and Gates Philanthropy Partners.

GPP: Let’s start with the basics. Your organization works on mosquitoes. Is it true that mosquitoes are the most dangerous animal on earth?

Scott O’Neill: Yes, mosquitoes kill about 725,000 people every year, which makes them humanity’s deadliest foe. But it’s important to remember that there are more than 3,500 known species of mosquito, and only a few dozen of those species bite people and transmit pathogens to humans.

One group of mosquitoes, known as the anophelines, is primarily responsible for transmitting malaria, which is the deadliest mosquito-borne disease. Malaria claims the lives of about 400,000 people each year. Most of these deaths occur in rural areas of sub-Saharan Africa among young children and women of childbearing age. Thankfully, there has been remarkable progress in bringing malaria better under control in recent decades.

The mosquito that we focus on at the World Mosquito Program is called Aedes aegypti, and unlike anopheline mosquitoes, this one loves big cities and has spread across the world’s tropical and subtropical regions.

Aedes aegypti is especially dangerous to humanity because it has adapted itself to our lifestyle. It breeds easily in discarded waste and plastic containers, and it prefers to bite people rather than animals. It has also developed a strong resistance to the pesticides we use to keep insects away from us.

And Aedes aegypti is extremely effective in transmitting viruses from human to human. It is the primary source of several deadly and debilitating diseases, including dengue, chikungunya, Zika, Mayaro, and yellow fever.

So, Aedes aegypti – just by itself – poses a major threat. Every year, it infects up to 400 million people with dengue, and about 50 million people become seriously ill. Global dengue incidence has grown 30-fold over the past half-century, and more than 4 billion people in 129 countries worldwide are currently vulnerable to the viruses transmitted by this one mosquito.

Unfortunately, that number will only see accelerating growth over the next few decades as climate change expands the geographic range of the species and rapid urbanization in the tropics increases the number of people who live in contact with this mosquito.

That’s why the World Mosquito Program exists. We’re committed to solving the challenge posed by Aedes aegypti, and we have created a unique solution – an incredibly cost-effective and environmentally sustainable approach to disease control that recruits the mosquito itself as an ally in the fight against disease.

GPP: What makes your work unique?

Scott O’Neill: Rather than vaccinate people against the diseases that Aedes aegypti can transmit to humans, we have developed a method that essentially immunizes Aedes aegypti against being infected by these viruses.

And if the mosquitoes can’t be infected, then the people they bite can’t get infected either.

GPP: What is this method?

Scott O’Neill: It’s an amazing bacterium called Wolbachia. Wolbachia is already commonly found in the cells of about 60 percent of all insect species. We know it’s safe for humans because it thrives in honeybees, butterflies, moths, and fruit flies. These species are an integral part of our lived environment, and we regularly consume Wolbachia through the fruits and vegetables we eat because these insects are an essential part of our food chain.

What makes Wolbachia a medical miracle is the fact that when it is introduced into Aedes aegypti, it effectively blocks the capacity of many of the viruses that make people sick from growing in the mosquito. And if the viruses can’t replicate, they can’t be transmitted to humans.

Our team successfully introduced a strain of Wolbachia taken from fruit flies into Aedes aegypti more than a decade ago, and over the past 10 years, we have shown that when Wolbachia-carrying Aedes aegypti are released into the environment, they collapse dengue transmission in that location. We are also confident that it is effective against chikungunya, Zika, and many other arboviruses based on our laboratory research.

GPP: You described Wolbachia as both cost-effective and environmentally sustainable. What is your evidence for this?

Scott O’Neill: Another amazing feature of Wolbachia is the fact that female mosquitoes that carry the bacteria pass it down to their offspring in her eggs. At the same time, if a male mosquito that carries Wolbachia mates with a female mosquito that lacks the bacterium, her eggs don’t hatch. So, by this mechanism, Wolbachia is able to establish itself within the wild mosquitoes in an area where it has been released until nearly all mosquitoes carry it.

There is also no evidence that mosquitoes are developing resistance to the bacterium. Similarly, we don’t see any evidence that viruses like dengue and Zika are developing resistance to Wolbachia.

The biologically self-sustaining features of Wolbachia create amazing health and economic dividends for people. If you can effectively eliminate these diseases with a one-time application of Wolbachia, then you are preventing tens of thousands of deaths, millions of hospitalizations, and billions of dollars in medical bills over time.

So, Wolbachia – if we can achieve its full potential and ensure that billions of people have access to the protection it delivers – could become one of the most transformative and cost-saving public health innovations in human history.

GPP: We’ve heard that a lot of organizations like yours have suffered setbacks due to the pandemic. What are you seeing?

Scott O’Neil: There is absolutely no doubt that the pandemic set back our progress in the short-term during 2020 and 2021. Our work relies on outreach, going to people’s homes, releasing mosquito eggs in their backyards. Intense social interaction has been a key element of our success, and we had to delay several projects in Laos, Sri Lanka, and other countries because of the very necessary social distancing steps required to reduce COVID-19 transmission in the communities where we work.

But we were also incredibly lucky. When the pandemic hit, we were in the process of completing our gold-standard randomized controlled trial for Wolbachia in Yogyakarta, Indonesia. We were able to collect enough of the data we needed to demonstrate conclusively that Wolbachia is a safe and effective method of dengue control and reduction, and we published those results last year in The New England Journal of Medicine. The study showed that Wolbachia collapsed dengue incidence by 77% and dengue-related hospitalizations by 86%, and the data suggest that Wolbachia will effectively eliminate local dengue transmission in the next few years.

Those results convinced an expert panel to advise the World Health Organization to publish guidance for countries on how they can adopt Wolbachia as the first proven effective method of dengue control in human history. We expect that WHO will release that guidance in the next few months.

So, we believe that 2022 is going to be an exciting year for Wolbachia, dengue control, and WMP. We’re optimistic that countries will embrace this method, and we are committed to transferring our technology and our knowledge to LMIC partners at the lowest possible cost. We’re eager to work with governments, corporations, philanthropies, and development finance institutions to create the financing that countries will need to take Wolbachia to scale at an affordable cost that pays for itself over time.

GPP: What’s on the horizon for your organization?

Scott O’Neill: We have finished the hard work of demonstrating that power and potential of Wolbachia as a game-changing public health tool. Now the truly hard part begins, which is ensuring that this novel approach to disease control, which has so far reached 8 million people across 11 countries, becomes affordable and accessible to the billions of people worldwide who could benefit from it.

Our organization plans to facilitate the scaling up of this intervention globally, not through our own growth but through partnership with other organizations in key geographies to ensure the technology is successfully transferred and utilized effectively in the areas where these diseases cause so much suffering.

We’re feeling the energy and excitement for our method building. We are confident that the world is looking for a win after suffering through the challenges of a global pandemic. We are truly excited about the next few years and eager to have new partners join our cause.