A mosquito sitting on human skin.
Credit: Pixabay
Along hundreds of miles of Lake Victoria’s shoreline in Kenya, a squadron of young scientists and an army of volunteers are waging an all-out war on a creature that threatens the health of more people than any other on earth: the mosquito.
They are testing new insecticides and ingenious new ways to deliver them. They are peering in windows at night, watching for the mosquitoes that home in on sleeping people. They are collecting blood — from babies, from moto-taxi drivers, from goat herders and from their goats — to track the parasites the mosquitoes carry.
But Eric Ochomo, the entomologist leading this effort on the front lines of global public health, stood recently in the swampy grass, laptop in hand, and acknowledged a grim reality: “It seems as though the mosquitoes are winning.”
Less than a decade ago, it was the humans who appeared to have gained the clear edge in the fight — more than a century old — against the mosquito. But over the past few years, that progress has not only stalled, it has reversed.
The insecticides used since the 1970s, to spray in houses and on bed nets to protect sleeping children, have become far less effective; mosquitoes have evolved to survive them. After declining to a historic low in 2015, malaria cases and deaths are rising.
Climate change has brought mosquitoes carrying viruses that cause dengue and chikungunya, excruciating and sometimes deadly fevers, to places where they have never been found before. Once a purely tropical disease, dengue is now being transmitted in Florida and France. This past summer, the United States saw its first locally transmitted cases of malaria in 20 years, with nine cases reported, in Texas, Florida and Maryland.
“The situation has become challenging in new ways in places that have historically had these mosquitoes, and also at the same time other places are going to face new threats because of climate and environmental factors,” Ochomo said.
Scientists around the world are pressing hard for new solutions, including novel technologies that Ochomo is testing. They have developed some promising approaches, including a new generation of tools that modifies mosquitoes biologically, and genetically, to block disease.
But such efforts have been stymied by cost and regulatory hurdles. The process for getting any of these tools to the places where children fall ill with each new season of rain involves years of testing and regulatory reviews that are painfully slow and badly underfunded.
“It’s just ridiculous how much time we are wasting before we can get into the field and actually start saving lives,” said Bart Knols, a Dutch vector biologist who runs mosquito-borne disease elimination projects across Africa, Asia and the Caribbean.
The biggest killer
Malaria has killed more people than any other disease over the course of human history. Until this century, the battle against the parasite was badly one-sided. Then, between 2000 and 2015, malaria cases dropped by one-third worldwide, and mortality decreased by nearly half, because of widespread use of insecticides inside homes, insecticide-coated bed nets and better treatments. Clinical trials showed promise for malaria vaccines that might protect the children who make up the bulk of malaria deaths.
That success lured new investment and talk of wiping the disease out altogether.
But malaria deaths, which fell to a historic low of about 575,000 in 2019, rose significantly over the next two years and stood at 620,000 in 2021, the last year for which there is global data.
There were more cases of dengue in Latin America in the first half of this year — more than 3 million — than in all of 2022. Bangladesh is in the grip of its largest-ever dengue outbreak, with 120,000 cases by the end of August. Cases of and deaths from chikungunya and other mosquito-borne infections have started rising, too, in many regions of the world.
One of the main reasons is that mosquitoes are highly adaptable. As more and more people are protected by nets or sprays at home, mosquitoes have begun to bite more outdoors and in the daytime, instead of indoors and at night, the historic pattern of the malaria vector species in Africa. Because the genetic makeup of mosquitoes evolves quickly in response to changing environmental conditions, they have also developed resistance to the class of insecticides in wide use — while the malaria parasite itself is increasingly resistant to the once highly-effective drugs used to treat it.
And a new mosquito that thrives in urban areas has come from Asia to Africa, where the spread of malaria had always been confined largely to the countryside. That change has made more than 100 million additional people vulnerable to mosquito-borne infections, researchers at the University of Oxford recently estimated.
The multiplying risks, experts say, mean there’s an urgent need for a method to protect people from all mosquitoes — one that will help defend against malaria, but also dengue, yellow fever and whatever pathogen lurks around the corner. (Only female mosquitoes bite; they need the protein in blood to produce eggs.)
But it takes a decade or more to design, develop, test and produce a new technology or intervention. Contrast that with the six-week life spans of mosquitoes, which are constantly evolving to elude the ways we try to kill them.
The bulk of the money for these efforts to date has come from high-income nations and private philanthropists, but funding levels have plateaued. Multiple researchers said it was increasingly difficult to motivate the kind of investment they need for large-scale trials of new methods.
“Sooner or later, funding bodies are going to divert that money to other things,” Knols said. “They’re going to say, ‘We’re putting it into agriculture, or into schooling.’”
A new problem
In the towns and villages of Busia County in Kenya, the roads begin to fill while the sky is still the streaky purple of dawn, with farmers on the way to their fields, children in freshly pressed uniforms walking to school and moto-taxi drivers reporting to the market.
Ochomo’s research has found that the mosquito Anopheles funestus is feasting on them: The species, once thought to bite mostly sleepers in their beds at night, now bites outside in the daytime.
Four in 10 people on these red-dirt roads are carrying the malaria parasite, even if they don’t have symptoms, studies by Ochomo and his colleagues have found. Some outdoor and daytime biting was likely happening all along, but no one was really tracking it because the focus was on the vulnerable sleepers.
Twenty years ago, in the early days of the mass distribution of bed nets, malaria case rates plunged immediately, and there was an optimism that the nets might be enough, said Audrey Lenhart, the chief of entomology at the U.S. Centers for Disease Control and Prevention. Instead, she said, they have helped to create a new problem.
“Think about it: You put bed nets everywhere, then the mosquitoes that bite people inside, they’re going to die out,” Lenhart said. “The ones that are going to survive are the ones that are biting people sitting outside, biting livestock, the ones that aren’t in the houses, right? So then those are the ones that are reproducing and keeping the population of mosquitoes there.”
Insecticides that don’t work
Most of the current insecticides in use are pyrethroids, which were developed in the 1970s and derived from the chemical compounds in an ancient mosquito deterrent made by crushing aster flowers. They have been used for everything, including bed nets and for spraying on walls.
With mosquitoes around the world now highly resistant to them, there is an urgent search for something new.
In 2005, the Bill & Melinda Gates Foundation invested $50 million in a project called the Innovative Vector Control Consortium to search for effective insecticide compounds. The consortium asked large agrochemical companies to look in their chemical libraries for molecules that might affect mosquitoes in novel ways and be safe and durable enough.
“We started with 4-1/2-million compounds, and we’re down to four,” said Nick Hamon, who recently retired as the consortium’s CEO.
To work as a new insecticide, compounds have to be safe for humans, come in solid form and not be water soluble. And they have to kill mosquitoes in a substantively different way than pyrethroids do, because mosquitoes develop resistance not just to an individual chemical, but to the way the chemical kills them.
Companies must now complete the safety and testing process on the only four compounds that tick all those boxes. It is intensely costly and slow, said Susanne Stutz, the chief chemist at the German chemical company BASF.
“It’s always a race with the mosquito, who is faster: Usually, the mosquito wins because it develops the resistance much faster than new products come out,” she said.
The World Health Organization requires two large randomized clinical trials, carried out in two different geographic and epidemiological settings, showing a significant positive impact on public health in both, before it will recommend use of a new intervention against mosquitoes. The organization says the policy is designed to make sure that countries with limited means are making the best decisions about where to spend their money and to ensure that products are backed by rigorous evidence. Yet the world’s multiplying mosquito problems increasingly require solutions tailored to specific situations: What works to protect children in the African Sahel won’t be what works to protect loggers in forests in Cambodia.
Ochomo is the principal investigator on two large randomized clinical trials of mosquito interventions. In one $33 million project, researchers are testing the effectiveness of spatial repellents — squares of plastic film that can be hung on the walls inside homes and that dispense low doses of a chemical that confuses mosquitoes and prevents them from biting — in both dengue and malaria risk areas.
S.C. Johnson & Son Inc., the Wisconsin-based company that developed the spatial repellent being tried in Kenya, has donated millions of dollars in products for testing. Such largess is unusual — and not a sustainable pathway for vector control research, said John Grieco, a professor of biological sciences at the University of Notre Dame who coordinates the multicountry spatial repellent trial, which is also running in countries including Mali and Sri Lanka.
The spatial repellents and most other new tools are commodities: items that have to be bought, then bought again six months or a year later. The protection they offer is temporary, as is the funding that allows for their purchase.
The Gates Foundation, the major backer of most of the clinical trials of the commodities, has also had to cover most of the cost of BASF’s testing of new chemicals for use on bed nets, because there is not sufficient profit incentive for a private firm to do it, Stutz said.
“How do you keep the companies that know how to innovate in this space?” Hamon asked. The Innovative Vector Control Consortium lost one of its key industry partners in 2017.
“They just said, ‘We can make more money somewhere else,’” Hamon said.
Some experts believe the emergence of dengue fever, and now malaria, in middle- and high-income countries could generate new funding because it creates a wealthier market that may spur new corporate investment.
Skeptics in the entomology world look at the race for new commodities, and suggest it ignores a lesson from history: They say that only the same strategies that high-income nations used more than a century ago will once again give humans the edge over mosquitoes. In southern Italy and the American South in the early 1900s, and in Brazil in the 1950s, it was large-scale environmental management that made a difference, said Silas Majambere, a Burundian vector ecologist who has worked all over Africa and Asia.
That means draining breeding sites, spraying larvicides (which are biological toxins and don’t cause resistance) on water that can’t be drained and moving homes out of swampy areas. Those steps won’t help combat urban mosquitoes. To protect against them, people need screened windows and solid roofs: better houses.
“If we had spent the last 40 years doing these things, with the same budget, where would we be today?” Majambere said.
Hope and challenges
While malaria cases are far lower than they were 20 years ago in the Busia area, the stalled progress means the disease continues to erode family health, income and futures.
“When there is a malaria case in the house, it suspends life,” said Mary Oketeti, a farmer who lives about an hour’s drive outside the town of Busia. She gets malaria three times a year, and her 12-year-old daughter twice as often as that. The family then has to spend what is needed for treatment.
“If there’s a chicken in the house you sell it,” she said.
A chicken might be worth 600 Kenyan shillings, or $5; a trip to the medical clinic, with transport, a diagnostic test and drugs for malaria, will cost at least that much. Repeated bouts of malaria keep children out of school and adults from working; they wipe out savings. Oketeti said she must stay home from the fields she farms to care for a sick family member for a few days every month.
Ochomo and his team recently received data from the midpoint of the clinical trial of spatial repellents. Malaria cases were significantly lower in families that had them compared to those that had devices that used placebo repellents. If that trend holds, the next challenge will be convincing the WHO to endorse the use of spatial repellents, then the Kenyan government to buy them.
It won’t be hard to convince people in Busia to use them, though, he said.
“People already know that nets are not enough, they need something more, and they’re happy to see us,” he said. “They say, ‘Finally, someone is coming to try to help with this.’”