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.
CHAPTER 25
They try to have tea with your immune system.