Chloroquine works its way into Plasmodium and bonds with the hemoglobin core before the parasite can neutralize it. In its new form, the compound won’t fit on the end of a hemozoin chain, and the parasite’s enzymes can no longer react with it. Instead it builds up in Plasmodium’s membrane and makes it leaky. The parasite can no longer pump in the atoms like potassium that it needs, or pump out the ones that it has to get rid of, and it eventually dies.
Now huge parts of the globe harbor malaria that’s chloroquine-proof. In the late 1950s, two chloroquine-resistant parasites were born—one in South America, the other in Southeast Asia. Researchers aren’t exactly sure what makes them so stubborn, but they suspect that they have a mutant protein that snags chloroquine before it penetrates too deeply into the parasite. These mutants have probably cropped up regularly for thousands of years, but the odd proteins they produced served no good purpose. They probably even slowed down the parasite’s feast of blood, so they were squelched by natural selection.
But starting in the 1950s, any parasite that could block chloroquine had plenty of space—human bodies—for colonizing. Year by year, the children of those two Plasmodium mutants spread from their homelands. The South American mutant spread to cover every malarial region of the entire continent. The Southeast Asian mutant, meanwhile, was even more cosmopolitan: by the 1960s it had overrun Indonesia and New Guinea to the east, while to the west it spread in the 1970s through India and the Middle East. In 1978, the first record of this Southeast Asian form was recorded in East Africa, and in the 1980s it had made its way to most of sub-Saharan Africa. Now it’s much harder to stop the spread of malaria because other antimalarial drugs are more expensive, and resistant strains of Plasmodium are rising up against them as well.
The resurgence of parasites like Plasmodium has made parasitologists yearn for a vaccine. But even though vaccines work well against some viruses and bacteria, there’s no commercially available vaccine against a eukaryote. None. The problem is that eukaryote parasites are complex, evasive creatures. They go through different stages within their host, one stage looking nothing like the next. Protozoans and animals are accomplished at fooling our immune systems—just consider the way trypanosomes can peel off their molecular fur and grow one with a completely different pattern of chemical stripes, the way blood flukes snatch our own molecules for a mask while producing other chemicals that turn us against ourselves.
The first attempts to make parasite vaccines were crude affairs. Scientists would destroy live parasites with radiation and then inject their remains into lab animals. They provided only a little protection. In the last twenty years, scientists have learned how to tailor their vaccines much more carefully. They’ve turned their attention from entire parasites to single molecules the parasites carry on their coats. Their hope has been to find a handful of molecules that the immune system can use to prime itself for fighting these invaders. But still the failures have kept coming. The World Health Organization organized an aggressive campaign to create a schistosomiasis vaccine in the 1980s. They backed not one molecule but six, each tested by a squadron of immunologists. None of them offered any significant protection, so the grand scheme has been scrapped as the vaccine developers look for new molecules.
Yet, parasites do not by definition defy vaccines. It’s still possible that there is a molecule they simply can’t live without, that the immune system can identify regularly enough to use as a guide for their attacks. In 1998, human trials began for a vaccine for malaria created by scientists with the United States Navy. Their vaccine is even more sophisticated than current ones. They want to get the human immune system to attack Plasmodium at its early stage in the liver cell. The liver cells display bits of Plasmodium’s proteins in the receptors for major histocompatibility complex (MHC) on its surface. Normally our bodies can’t fight malaria at this stage, because by the time killer T cells have recognized the fragments and multiplied into a parasite-killing army, the Plasmodium has already escaped the liver and slipped into the bloodstream.
But if the killer T cell were already primed to recognize those fragments, they would be able to start destroying the infected liver cells immediately. To create an army of these T cells, the navy scientists want to give people a false case of malaria. They have fashioned a sequence of DNA that they are injecting into the muscles of volunteers. The DNA makes its way into the muscle cells, where it starts making the same protein that is made by Plasmodium and displayed by liver cells. The muscle cells should, in theory, carry this vaccine protein to their own surface, and killer T cells that come across it will be able to fight off an actual infection when it comes.
It’s a long way, though, from human trials to an actual vaccine campaign—particularly against diseases such as malaria and schistosomiasis that affect hundreds of millions of people in the poorest parts of the world. “What’s the best you could expect from a vaccine?” asks Armand Kuris, who has spent a large part of his career looking for ways to control schistosomiasis. “A molecular biologist will say, ‘It’s expensive, it will require revaccination every five to seven years, it will require perfect cold delivery.’ That means refrigeration from its manufacture to the point when you’re taking out a vial and sticking a syringe into it. Did you ever get a vaccination for smallpox? I received a vaccination on the border of Costa Rica where the nurse had the vaccine in a shot glass and tattooed me with a sewing needle. Now that’s a vaccine.” He points out that praziquantel, the cure for schistosomiasis, costs twenty dollars. “In Kenya in the villages where I work, the best-off families may be able to get the drug for a favored child. If that’s economically impossible, then if I gave you a vaccine, what the hell could you do with it? I’m not saying don’t do any research in it. The navy may have to go to a place with malaria—Peace Corps workers, diplomats … but in terms of the 200 million people who suffer from schistosomiasis, the vaccine has no chance of working. And yet my calculation is that three-quarters of the money spent on schisto in the past twenty years has been spent on vaccines.”
Even if researchers could produce a vaccine that met Kuris’s shot-glass standard, the parasites might well find a way around it. The World Health Organization has decided that even if a schistosome vaccine provided only 40 percent protection, it would be worth backing. That doesn’t mean that 40 percent of the 200 million people with schistosomiasis would be rid of their parasites. That means that each person would lose 40 percent of the worms inside his veins. It sounds like a worthy goal, but it ignores the sophistication of schistosomes. These flukes can sense how many of their fellow flukes are in their host, and as that number gets higher, each female produces fewer and fewer eggs. It’s probably a mechanism the blood flukes have evolved to take care of their hosts. If every female were to crank out as many eggs as she possibly could, they’d cause so much scarring to the host’s liver that the host might die. A vaccine that killed 40 percent of the worms in a person might create the opposite situation: the surviving schistosomes would sense that they had less competition and ratchet up the egg production, making the disease worse.