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.
On June 22 I returned to the National Institutes of Health. In the interim, Chris Fisher had also been through the treatment, while most of the others were scheduled after me. His initial reaction to the drug had been as bad as Dave’s—sudden pain, a feeling of pressure and suffocation, an
d a panicked feeling that he might be dying. But luckily those side effects went away in less than ten minutes. Chris’s body had tolerated the amphotericin better than Dave’s, and he managed to get the full, seven-day course. Even so, he had a rough time. The treatment left him feeling nauseated, exhausted, beaten up, and “totally without ambition.” After he returned to Colorado he got a rash on his body so terrible that the NIH doctors wanted to hospitalize him (he refused). He was sick all summer and unable to work into the fall semester, which caused him professional difficulties with his university department. The leish ulcer then started to come back, and only went away after Chris applied heat treatments to it. Over a year later, Chris’s rash still hadn’t completely healed.
Dave’s and Chris’s experiences were in the forefront of my thoughts as I filled out the usual paperwork at the NIH. My wife, Christine, had come with me, and we were escorted into one of the hospital rooms used for infusions. It was a very pleasant space, although the furniture was bizarrely oversized. I felt like I’d landed in Swift’s imaginary kingdom of Brobdingnag. The nurse explained that the NIH was researching morbid obesity, and we were in one of the rooms specially built for those patients.
I took my seat in the infusion chair, stressed and anxious. Since the infusions took a total of six to eight hours a day for seven days, I had brought a backpack stuffed with twenty pounds of my favorite comfort books, far more than I could ever read—Edgar Allan Poe, Arthur Conan Doyle, Wilkie Collins. I imagined being trapped for hours with a terrifying Nurse Ratched hovering about. But a perverse part of me was also curious about the effects of the drug. What would it be like to believe I was dying? Maybe I’d see the face of God, or the light at the end of the tunnel, or the Flying Spaghetti Monster.
An agreeable, totally un-Ratched nurse arrived, inserted the IV, and drew blood; then she started me on the saline drip. My actual ulcer would not be messed with, although they would examine it every day to see if it began to heal.
The bloodwork came back an hour later and all was good: I had strong kidney function. With both Drs. Nash and O’Connell in watchful attendance, the evil brown bag of amphotericin B was hung on the IV rack next to a bag of Benadryl. Fifteen minutes of a Benadryl infusion left me feeling groggy, and then the stopcock was turned and the ampho started down the tubes.
Dave, our honorary Italian, had compared it to limoncello. To me it looked like the color of urine. Watching it creep down the tube toward my vein only raised my anxiety levels, so I forced myself to avert my eyes. I chatted with the doctors and my wife, pretending nothing was happening, but all the while bracing myself for the sudden pain, the pressure, my head erupting in flames, God, or Baal. I could see my two doctors were also chatting about nothing with excessive cheer, trying to cover up their own nervousness.
The yellow liquid went in and then—nothing happened. I experienced none of the side effects that Dave and Chris did. It was a total anticlimax. Everyone was relieved, but I was also slightly disappointed.
From there, my treatment proceeded uneventfully. I arrived at the clinical center every morning around eight, got stuck with an IV, was subjected to a battery of blood tests, and then infused. After the third day, I asked my doctors to stop the Benadryl (aimed at blocking an allergic reaction to the drug) because it made me sleepy. They did so with no problems. After a few days the inevitable nasty side effects of the ampho did begin to creep in: I got a persistent headache and started to feel nauseated. Beyond that, I had a vague mental uneasiness that something was going badly wrong inside me, but I couldn’t put my finger on what. The side effects worsened until the sixth day, when I felt I was dragging around the world’s worst hangover—headache, nausea, lethargy, and muddled thinking. Toward the end of my treatment, Mark Adams, the sound engineer, started his. Mark had been on both expeditions, the 2012 lidar search and the 2015 jungle foray. He had been one of my favorite people, soft-spoken and cheerful even while hauling forty pounds of sound equipment and a long boom mic through dense jungle in the pouring rain. We asked to be together in the same room, where we passed the time chatting and reminiscing about our adventures. Mark also tolerated the ampho well, experiencing none of the scary side effects.
Awful as I felt, the nausea and apathy were among the most common and mildest side effects of amphotericin. I was extremely lucky. My doctors gave me anti-nausea drugs, ibuprofen, and a vile-tasting drink to restore my electrolyte balance. But on the sixth day, Nash and O’Connell told me my kidney function had dropped into the danger zone and they were going to discontinue the infusions. They wanted me to wait and have the final infusion after my kidneys had recovered. I received that infusion a few weeks later, closer to home, arranged by the NIH and my brother David, who is a doctor.
The hangover went away after about a week of the initial round, and in the following months the lesion dried up, flattened out, and turned into a shiny scar. At one point I asked Dr. Nash about the risks of going back into the jungle, which, despite everything, part of me remained eager to do if I could. He said that research indicated that 75 to 85 percent of people who got leish were thereafter immune; he felt I should be much more concerned about other diseases rife in the area for which there are no preventatives—dengue fever, chikungunya, and Chagas’ disease. (At this point Zika had not yet arrived in Honduras.)
I returned to the NIH three months later, in September 2015, for a follow-up. Nash and O’Connell looked me over, poked at the scar, took some blood, and concluded that the disease had been drubbed into remission. I was cured, at least as far as was possible. While neither doctor could talk about the other members of the expedition due to medical confidentially, I did learn that I was one of the lucky ones, and that some of my fellow travelers (who have asked me not to identify them) have not been cured and require additional courses of treatment using miltefosine or other drugs. Some are still struggling with the disease. (Unfortunately, at the time of this writing, my own leish appears to be returning, although I haven’t told my doctors yet.)
Meanwhile, I had become curious about the NIH’s leishmania research, said to be the most advanced in the world. I wondered what their scientists had learned, if anything, from studying our particular parasite. So I took the opportunity to pay a visit to the leishmania laboratory on the campus, where researchers maintain a live colony of infected sand flies and mice. It is one of the few laboratories in the world breeding and raising infected sand flies—a tricky and dangerous business.
The leish lab is officially called the Intracellular Parasite Biology Section. It keeps a biological archive of live leishmania parasites of many different strains and species, some going back decades. The parasites are cultivated from biopsied tissue samples taken from people like me. These bits of tissue are placed on a blood agar plate, where the parasites are teased into multiplying. Then they are transferred into bottles filled with a liquid nourishing medium and stored at seventy-seven degrees, the body temperature of the sand fly. In the bottles, the parasites go about their business, fooled into thinking they are swimming around inside the gut of a host fly.
The sand fly has a much lower body temperature than human beings. Cutaneous and mucosal leish parasites do not like the higher heat of the human body; that is why they normally remain on the skin or seek out the mouth and nasal membranes, where the body temperature is a few degrees lower. (This is not true of visceral leish, which tolerates heat and goes deep into the body.)
Every strain in this library of parasites must be regularly recycled through mice to keep up its virulence. Otherwise it becomes “old,” weak, and useless for study. The protocols for animal research try as much as possible to avoid inhumane treatment; the suffering of the mice involved in the research, while mitigated as much as possible, is necessary in order to study and combat the disease. There are no alternatives to live research.
The sand flies and mice are kept in a biosafety level 2 lab. BSL-2 is for biological agents of “moderate potential hazard.” (There are four
biosafety levels, BSL-1 to BSL-4.) I arrived at the lab during mealtime for the sand flies. A lab assistant brought me into the BSL-2 lab, which was a small room with a sealed door, a biohazard warning sign pasted on it. Below the symbol, taped to the door, was a soiled piece of paper with a giant picture of a sand fly and the name PHIL’S PHLY PHARM written underneath. Phil, I learned, was a scientist, long gone, who had helped develop the sand-fly feeding techniques.
No biohazard suit was necessary. I entered with some trepidation, glancing around nervously for loose flies, but they were safely shut away in stainless-steel, climate-controlled lockers. However, outside the lockers, a clear plastic box sat on a lab table, and inside was an off-putting sight: two anesthetized mice lying belly up, paws in the air, twitching. They were completely covered with feeding sand flies, whose tiny guts were expanding into bright red berries of blood. I shuddered, thinking of lying in my own tent, belly up and asleep, while the sand flies sucked my blood. These particular sand flies had not yet been infected with leish; once infected, they are handled more cautiously, not only because they can transmit disease but because they have become more valuable to science.
Later, these sand flies would be infected artificially, a complicated process. A delicate, hand-blown, tiny glass bottle has a piece of raw chicken skin stretched over it like a drumhead. This skin is moistened with mouse blood to fool the flies into thinking it is mammalian skin. The liquid inside the bottle is also mouse blood, seeded with the parasite. The sand fly jabs its proboscis through the chicken skin into the bottle and sucks up the blood and parasites. Once a sand fly is infected, the lab workers must then coax it into biting a live mouse, to transfer the infection. The target mouse is put in a tight Plexiglas box and its ear is held in a clamp attached to a small vial containing the infected flies. The hungry females fly down a tube, land on the mouse’s ear, and suck blood, transmitting the parasites to the mouse.
The Lost City of the Monkey God Page 24