Dr. Nash had spent almost his entire medical career in the parasitology section of the NIH—forty-five years—going back, he said, to the time when parasitology was “the backwater of science, no one was interested, and no one would work with you.” Because most people who get parasites are poor, and because infectious-disease medicine is not usually fee-based, parasitology is one of the lower-paying of all the medical specialties. To go into the field, you have to truly care about helping people. Your extremely expensive, ten-year medical education gives you the privilege of working long hours for modest pay among the poorest and most vulnerable people in the world, encountering a staggering amount of misery and death. Your reward is to relieve a small bit of that suffering. It takes a rare kind of human being to become a parasitologist.*
Nash’s early research focused on schistosomiasis and then giardia, a common, worldwide, waterborne parasite. Today the main focus of his work is a parasitic disease called neurocysticercosis, in which the brain is invaded by tapeworm larvae that originate in undercooked pork. The larvae circulate in the bloodstream and some get stuck in the tiny vessels in the brain, where they form cysts, leaving the brain peppered with grape-sized, fluid-filled holes. The brain becomes inflamed and the victim suffers seizures, hallucinations, memory failure, and death. Neurocysticercosis affects millions of people and is the world’s leading cause of acquired epileptic seizures. “If only we had the smallest fraction of the money that is devoted to malaria,” he declared to me in anguish, “we could do so much to stop this disease!”
In our first meeting, Nash sat me down and explained why he thought our team had become infected, how leishmaniasis works, what its life cycle is, and what I had to expect from treatment. The disease requires two animals: a “reservoir host”—an infected mammal whose blood is teeming with the parasite—and a “vector,” which is the female sand fly. When the sand fly bites a host and sucks its blood, it also draws in parasites. Those parasites proliferate in the sand fly’s gut until it bites another host. The parasites are then injected into the new host, where they complete their life cycle.
Each host animal lives out its life as a Typhoid Mary, infecting the sand flies that drink its blood. The parasite, while it can devastate a human being, generally does not “cost” the host animal very much, although some host mammals get lesions on their noses. A good guest does not burn down the house he’s staying in; leishmania wants its host animal to live long and prosper, spreading as much disease as possible.
In the isolated valley of T1, far removed from human habitation, sand flies and an as-yet-unknown mammalian host—it could be mice, rats, capybaras, tapirs, peccaries, or even monkeys—had been locked in a cycle of infection and reinfection going on for centuries. “And then,” said Nash, “you intruded. You were a mistake.” By invading the valley, we were like clueless civilians wandering onto a battlefield and getting shot to pieces in the crossfire.
When an infected sand fly bites a person, the fly unleashes hundreds to thousands of parasites into the person’s tissue. These tiny single-celled animals have flagella so they can swim around. They are small; it would take about thirty to span a human hair. But they are positively gargantuan compared to bacteria and viruses that cause disease. Almost a billion cold viruses, for example, could be packed into a single leishmania parasite.
Because it is a complex, single-celled animal, its methods are more subtle and devious than a virus or bacterium. When a sand fly injects leishmania, the human body, sensing the intrusion, sends an army of white blood cells to hunt down, swallow, and destroy the parasites. White blood cells, which come in many types, usually deal with bacteria and other foreign bodies by engulfing and digesting them. Unfortunately, this is exactly what the leishmania parasite wants—to be swallowed. Once inside the white blood cell, the parasite drops its flagellum, becomes egg-shaped, and starts to multiply. Soon the white blood cell is bulging with parasites like an overstuffed beanbag, and it bursts, releasing the parasites into the victim’s tissues. More white blood cells rush to attack and engulf the loose parasites, and they are in turn hijacked into producing more parasites.
The ulcer that forms around the infected area isn’t caused by the parasite per se, but by the body’s immune system attacking it. The inflammation, not the parasite, is what eats away the person’s skin and (in the mucosal form) destroys the face. The immune system goes nuts trying to get rid of the parasite that is blowing up its white blood cells, and this fight trashes the battlefield, inflaming and killing the tissues in the bite area. As the parasite slowly spreads, the lesion expands, destroying the skin and leaving a crater exposing the raw flesh below. The ulcer is usually painless—nobody knows why—unless it occurs over joints, when the pain can be intense. Most deaths from mucosal leish occur from infections invading the body through this unprotected doorway.
Nash then talked about the drug that I would be taking, amphotericin. He said it was the gold standard, the drug of choice, for this kind of leish. While miltefosine was a newer drug and could be taken in pill form, he didn’t want to use it. And besides, there was none available.* There had been too few clinical trials to make him comfortable with it, and in one trial in Colombia it seemed to be ineffective against L. braziliensis. He also said you never really knew what kind of side effects might pop up until at least ten thousand people had taken a drug, and miltefosine had not reached that benchmark. He had had long experience with amphotericin B, and it produced an approximately 85 percent remission rate, which was about “as good as it gets” in any drug treatment. The drug works by binding to the parasite’s cell membrane and tearing open a tiny hole in it, causing the organism to leak and die.