When your goal is just to reduce illness and death caused by malaria, you’re likely to focus most of your energy on Plasmodium falciparum — the deadliest and most common parasite behind the disease. But when you’re trying to end malaria for good — eradicate it from the face of our planet — you have to tackle malaria in all its forms, including P. vivax. This presents additional challenges that require innovation.
One of the things that makes P. vivax so insidious is that, in addition to the active parasite that makes you sick, it also has “sleeper cells,” called hypnozoites, that may linger in your body once you’ve been treated. They can stay in your liver for up to a year or longer until, with no warning, some of them wake up and cause a renewed bout of malaria. And people who experience this resurgence of parasites can become reservoirs of renewed infection for their families and their communities.
There are drugs that kill hypnozoites, but they can be toxic to a lot of people, so there’s still work to do. The problem with finding a drug that will help everyone is that, until recently, generating hypnozoites in a lab was impossible because researchers had to use cancerous liver cells as hosts, and after two or three days, these cells were no longer suitable for hypnozoite growth. Since a hypnozoite takes at least a week and a half to mature and reactivate, by the time the cancerous liver cells stopped being good hosts, the hypnozoites have not had sufficient time to reactivate.
Dr. Dennis Kyle, a parasitologist formerly at the University of South Florida, came to us with a big idea on how to solve this problem. His multidisciplinary team of engineers and biologists wanted to try, essentially, to build a section of a human liver in a lab, including capillaries, membranes, chambers, and a mechanism for blood to flow through them all. This would involve alternating layers of glass and plastic in which channels had been cut for blood to flow and healthy liver cells to grow, resulting in a structure less than 1.5 mm thick but complex enough to simulate the human liver — at which point he would have a perfect host to grow hypnozoites. There were many steps to the project and many ways it could fall apart at each step, but the proposal was so well designed that we couldn’t say no.
As Kyle and his partners, including engineers at Draper Lab in Cambridge, MA and Tampa, FL began work, they realized that some of the parts of the liver they’d imagined they’d have to create weren’t actually necessary to grow the hypnozoites — and, as they kept working, the list of parts that turned out to be unnecessary kept growing. What they eventually realized was that they didn’t need the capillaries, the membranes, the chambers, or the blood flow. All they needed was to confine healthy liver cells in the right way, and that would be enough. Designing the well plate (a very small version of a test-tube tray) was itself an incredibly complicated job, though, and they kept on making it better and better.
What Kyle and his team have ended up with is even more effective than they’d hoped. It used to be that, when researchers were trying to find drugs that killed sporozoites, they needed up to 500,000 of them to find out whether a single chemical compound could be the foundation of a new drug. With the well plate as Dr. Kyle has designed it, however, 500,000 sporozoites will allow researchers to test at least 100 chemical compounds. This is important, because sporozoites aren’t easy to come by — they have to be harvested from individual mosquitoes that have fed on malaria-infected blood.
Dr. Kyle, who is now at the University of Georgia, has already started testing compounds that have proven effective against other diseases, and by the end of the year he expects to have tested 12,000 such compounds to find out whether they can help us eradicate P. vivax. Not only that, he’s also working with companies to make the well plates widely available to researchers all over the world, which means even morepeople will be doing this testing.
Dr. Kyle’s success doesn’t mean we’ve defeated P. vivax. But it’s now a much fairer fight. We still need to find a compound that works well against hypnozoites — whether by killing them before they wake up, by waking them up and then killing them, or even by just keeping them dormant. From there to a medication that’s safe and effective is a long journey. Still, we’re a lot closer to a world where no child has to live at risk of malaria.