CHAPTER 24

My head felt like it was in flames.

The National Institutes of Health occupies a verdant campus of several hundred acres in Bethesda, Maryland. I arrived alone on June 1, a gorgeous summer day, the smell of freshly cut grass drifting in the air, birdsong pouring from the trees. Sandals and jeans seemed to outnumber lab coats, and the place had the relaxed air of a college. As I walked up the drive toward the clinical center complex, I could hear from faraway a lone bugler playing taps.

I entered the center, and after wandering around more lost than I’d ever been in the jungle, I managed to find the patient processing area. There I signed paperwork agreeing to be studied, and a kindly nurse took thirteen vials of my blood. I met Dr. Ted Nash and my second doctor, Elise O’Connell, and was reassured by their warmth and professionalism.

In the dermatology lab, a photographer arrived with a Canon digital camera. He affixed a little ruler just below the ulcer on my arm and took dozens of photographs. I was ushered into an examination room where the lesion was inspected by a gaggle of earnest medical students, who took turns peering, palpating, and asking questions. Next, in the biopsy lab, a nurse cut two wormlike plugs of flesh out of the lesion, and the holes were stitched up.

When the biopsy came back it would offer no surprise: Like Dave and everyone else, I had Leishmania braziliensis. Or at least that’s what the doctors initially believed.

Our primary doctor, Theodore Nash, was seventy-one years old. He did his rounds in a white lab coat with a roll of papers precariously shoved into a side pocket. He had curly salt-and-pepper hair brushed back from a domed forehead, steel-rimmed spectacles, and the kindly, distracted air of a professor. Even though, like most doctors, he was fantastically busy, his manner was unhurried and relaxed, and he was gregarious and happy to answer questions at length. I said I wanted to hear the straight story without any window dressing. He said that was how he preferred to work with all his patients. He was refreshingly, even alarmingly, direct.

The National Institutes of Health has been conducting clinical studies on leishmaniasis since the early 1970s, treating recent immigrants and people who had picked up the disease while traveling. Many of the patients were Peace Corps volunteers. Dr. Nash participated in the treatment of most of them. He had written the upgraded leishmaniasis treatment protocol for the NIH in 2001, and it is still in use today. He shifted treatment away from the antimonial drug, which he thought was too toxic, to amphotericin and other drugs, depending on the parasite species and the geographic variety. Nash knew as much about leish treatment as any doctor in the United States. This is not a simple disease, and treatment is more an art than a science. The clinical data aren’t deep enough to give doctors a precise formula, and there are too many forms of leish and many unknowns.

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.

Nash told me what I might experience in taking the drug. He didn’t sugarcoat his comments. The side effects of liposomal amphotericin, he said, can be dramatic and “are almost too numerous to mention.” There are acute reactions that occur instantly upon receiving the drug, and there are dangerous long-term side effects that occur days later. Many of these side effects are complex and poorly understood. When he started using it around fifteen years ago, things went well at first, and then, all of a sudden, his patients began to experience acute reactions when the drug went into the body. It turns out that some people tolerate the drug and some don’t. These reactions, he said, initially panicked him because they mimicked symptoms of an acute infection—fever, chills, pain, soaring heart rate, chest pressure, and difficulty breathing. On top of that, the drug had a mysterious psychological effect on a few patients. Within seconds of receiving the drug they became overwhelmed by a feeling of impending doom that, in the worst cases, made them believe they were actually dying. In those, he had to halt the infusion and sometimes administer a narcotic to calm down or knock out the patient. That acute reaction, however, usually went away quickly, and Nash emphasized that many patients experienced no reaction at all. I might be one of the lucky ones.

He reeled off other common side effects: nausea, vomiting, anorexia, dizziness, headache, insomnia, skin rash, fever, shaking, chills, and mental confusion; other physical effects include electrolyte imbalances, decreases in white blood cell count, and liver function abnormalities. These outcomes were so frequent, he explained, that I could expect to get at least some of them. But the most common and dangerous side effect is that the drug damages the kidneys, degrading renal function. The harm tends to be worse the older you are; old people, he said, lose renal function naturally as they age. I asked Nash if I was, at fifty-eight, in the “old” category, and he thought that was funny. “Oh, ho!” he cried. “So you’re still telling yourself you’re middle-aged? Yes, we all go through that period of denial.” As a general rule of thumb, he would stop administering the drug when kidney function had dropped to 40 percent of baseline.

The whole process, he said, is “stressful for the patient and stressful for the doctor.”

When I asked him if the disease was curable, he hemmed and hawed a bit. It’s curable in the sense that the symptoms go away. But it’s not curable in the sense that the body is completely rid of the parasite—what doctors call a “sterile cure.” Like chicken pox, which can come back years later as shingles, the parasite hides in the body. The point of the treatment is to beat down the parasite enough to allow the body’s immune system to take over and keep it in check. Rather than mounting a frontal attack on the body, a Pickett’s Charge, the parasite hides and shifts about, sniping from cover. But white blood cells talk to each other using chemicals called cytokines. The cytokines tweak how white blood cells respond to a leishmania attack, eventually “training” them to mount a better defense.

But the mucosal and visceral forms of the disease can come roaring back if your immune system goes downhill. That can happen, for example, if you get HIV or undergo cancer treatment or an organ transplant. In L. braziliensis, recurrences of the disease are not uncommon in people with good immune systems. But even in the best-case scenario your body must engage in low-level warfare with the parasite for the rest of your life.

While I was in the hospital for my biopsy, I visited Dave, who was recovering from his aborted treatment. He was installed in a large private room with a fine view of rooftops, trees, and lawns. Eager to see him for the first time since we left the jungle, I found him sitting on the side of the bed, dressed in a hospital gown. Even though I knew he’d been through hell, his appearance was a shock: Dave looked shattered, a far cry from the robust, sardonic professional who, festooned with cameras and cracking jokes, had a few months earlier tramped around the jungle in the pouring rain shoving lenses in our faces. But he managed to greet me with a wan smile and a sweaty handshake, not rising from the bed, and told me what had happened.

Because amphotericin damages the kidneys, before starting him on the drug, Nash and his team had analyzed Dave’s kidney (renal) function and decided it was not as strong as they would like. They checked him into the hospital for the duration of the treatment so that his renal function could be closely watched. There is a substance in the blood called creatinine, a waste product of muscle use, which the kidneys filter out at a regular rate. When creatinine levels rise, it means the kidneys are not functioning properly. By checking creatinine levels daily, the doctors at NIH can monitor how much kidney damage is taking place. In the early stages such damage is almost always reversible.

Dave then described what it was like to get the drug, which echoed many of Nash’s warnings. The total process, he said, took seven to eight hours. After the nurses settled him comfortably into a lounge chair and attached an IV, they conducted a battery of blood tests to make sure his numbers were good. Then they ran a liter of saline solution into his body, diluting his blood so that the kidneys would be able to flush the drug through quickly.

The saline drip took an hour, followed by a fifteen-minute infusion of Benadryl, to tamp down any allergic reaction he might have to the amphotericin. Meanwhile, the nurses hung an evil-looking opaque brown bag, which contained the liposomal amphotericin.

When all is ready, Dave said, they turn a valve that starts the amphotericin. The liquid is expected to spend three or four hours creeping out of the bag and into the patient’s arm.

“So what happened when you got the drug?” I asked.

“I watched that limoncello-colored solution come down through the tubes and go into me,” Dave said. “And within seconds—seconds!—of it entering my veins, I felt a big pressure on my chest and a pain in my back. I felt this profound tightness in my chest, with really difficult breathing, and my head felt like it was in flames.”

Dr. Nash had immediately stopped the flow of the drug. These were, in fact, common side effects of starting the infusion, caused not by the amphotericin itself but by the tiny lipid droplets that, for mysterious reasons, sometimes fool the body into thinking a gigantic foreign cellular invasion is taking place. The symptoms usually go away fairly quickly.

In Dave’s case, the doctors let him recuperate for a few hours, and then they pumped him full of more antihistamines and started him on the amphotericin again, at a slower rate. This time he made it through. They gave him a second infusion the following day. But late that evening, Dr. Nash came in with bad news: “You flunked amphotericin.” Dave’s creatinine levels had soared; his kidneys had taken a serious hit. The doctors had decided to halt the treatment for good.

They were going to keep him there, he said, for the rest of the week, monitoring his renal function to make sure he was properly recovering.

“So what now?” I asked. “How are you going to get cured?”

He shook his head. “Fuck if I know.” He said the doctors were going to wait and see if the two doses had knocked out the leish, which was possible but unlikely. It was a slow-acting disease and there was no need to rush into another potentially toxic treatment. In the meantime, the NIH would try to get the newer drug, miltefosine, for him. A course of miltefosine can cost close to twenty thousand dollars, compared to around six or eight thousand for ampho B. Even though miltefosine was unavailable in the States, Dr. Nash was going to see if it could be brought in under a special permit as an experimental treatment.

I had been listening to all this with rising dismay, realizing that I had no alternative but to take the same journey myself. My own treatment was scheduled for the end of the month.