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Malaria is one of the world’s leading causes of death in poor countries, killing a child under age 5 every two minutes. Affected countries spend $800 million annually on malaria prevention and control, and rich countries spend another $1.9 billion in aid for malaria prevention annually.
It’s making a difference. Deaths have been falling. The number of children under 5 killed by malaria has declined from 440,000 in 2010 to 285,000 in 2016.
That death toll is, of course, still too high, and for a long time researchers have been working on plans to eradicate malaria altogether. In the past couple of weeks, two different studies came out that propose promising new antimalarial interventions. In the first study, published in Nature Communications, researchers proposed a method to stop malaria from spreading to mosquitoes in the first place. In the second study, published in Nature Biotechnology, researchers demonstrated the success in a lab of an even more out-there approach: planting a deadly gene in mosquito populations, engineered to spread rapidly among successive mosquito generations and render the whole population infertile.
Stopping malarial transmission within the mosquito, rather than the human, is promising because it disrupts transmission at a key point of the parasite life cycle. Just as humans catch malaria from mosquitoes, mosquitoes catch it from humans. Even after a person has successfully fought off the virus or been treated for it, there’s a reservoir of dormant malarial parasites in their blood. Being dormant makes these forms of malaria very hard to target with drugs (which need to react chemically with the things they target), so while researchers have long wished there was a way to choke off the cycle of malarial transmission by destroying these dormant parasites, they’ve struggled to find one.
Researchers at Imperial College London took a new approach. They stimulated sexual development of dormant malaria parasites as it occurs in mosquitoes and then exposed the developing parasites to more than 70,000 compounds with the potential to halt the parasites’ development. Of those 70,000, only six were both active against the parasites and potentially safe to give to humans. “It was like finding needles in a haystack,” said lead researcher Dr. Jake Baum of the multi-year screening effort.
There are still a lot of challenges before the compounds identified in the study can be deployed in the field. Drug development is a complex, slow process, and testing new drugs for safety in humans is no different. The drugs would need to be stable enough to be given to a human and survive transmission into a mosquito. And to be an effective antimalarial intervention, the compound would also need to be cheap — for a malaria intervention to make a big difference, it needs to be scalable.
The other approach that saw a major breakthrough this week, gene drives, is further along but still far from being ready to deploy. Researchers have been working on the gene drive approach to malaria eradication for more than a decade and have already overcome enormous technical challenges. In this study, researchers wanted to make a gene for sterility spread rapidly through the population despite being exceptionally detrimental to its hosts — which isn’t how genetic transmission of traits works ordinarily.
Researchers used mathematical models to track how they expected a gene modification to play out in a real population, but the models often broke down in real life, with the mosquitoes evolving resistance within a few generations.
This time, though, the researchers pulled it off in the lab as well as in their computer simulations. The gene sequence they’d designed spread rapidly through the caged mosquito populations. Within seven to 11 generations, it had achieved 100 percent prevalence in the population and reduced egg production until the population collapsed. And there are promising signs that they’ve solved the problem of evolved resistance, as they observed no selection of alleles resistant to the gene drive.
Progress in the lab — but still a long way from success in the field
This is all great news — but it’s far from being something we can take to the field. The researchers got their results in 20-cubic-centimeter cages with a laboratory strain of Anopheles gambiae.
The real world is more complex in many ways. The vastly larger real-world populations of mosquitoes mean it’s likelier resistance will, somehow, crop up. It could be that the gene drive doesn’t work as well in real-world mosquito strains. The uncontrollable nature of gene drives, which are designed to spread, have prompted some to raise reservations about starting one.
Advocates for eradication consider it urgent to assuage those doubts without delaying progress — as delays will cost hundreds of thousands of lives — but still expect it to take a long time to get all the stakeholders on board. (Since gene drives spread through a population with no regard for national borders, every country with a malarial mosquito population is potentially a stakeholder.)
Target Malaria, which funded this research, is just now beginning efforts to release genetically engineered mosquitoes and is still years (perhaps decades) from releasing mosquitoes that have been targeted by genes like these.
Scientific approaches to eradicating malaria with new drugs and futuristic technologies are exciting, and some of them may eventually be ready for real-world deployment. However, breakthroughs tend to get more media coverage than the methods already tested, proven, and implemented, even though many of those breakthroughs will never make it to the field.
Distribution of insectide-treated bednets significantly reduces malaria, both directly (by protecting the people who sleep under them) and indirectly (by reducing the process of transmission throughout the population). Bednets aren’t nearly as exciting as gene drives, but they get results, reducing cases of malaria by half. With field deployment of exciting new technologies likely a decade or more away, there are a lot of lives to be saved just by consistently providing the options that already work.
More than that, the most crucial stakeholders for malaria eradication interventions are the people living in countries affected by malaria. Any intervention to tackle malaria is ultimately going to need their support. Supporters of gene drives are aware of this and have been actively involved with local partners, making the case for their intervention. Continuing to deliver on the interventions that work today should be seen as an integral part of the longer-term plan to eradicate malaria.
Ultimately, solving a public health problem as big as malaria requires both creative approaches and unflinching commitment to the approaches currently known to work best. Exciting as it is to see progress on some potentially game-changing approaches, it’s also more important than ever to continue to invest in effective interventions as breakthroughs work their way down the long pipeline to real-world deployment.
