The Lost City of the Monkey God

by Douglas Preston

  The final form of leish is the mucocutaneous or mucosal variety, the major New World form of the disease. It starts as a skin sore like the cutaneous kind. Months or years later, the sores can reappear in the mucous membranes of the nose and mouth. (The sores I had in my mouth, however, were probably unrelated.) When leish moves to your face, the disease gets serious. The ulcers grow, eating away the nose and lips from the inside and eventually causing them to slough off, leaving the face horrifically disfigured. The parasite continues to devour the bones of the face, the upper jaw, and teeth. This form of leish, while not always lethal, is the most difficult to treat, and the treatment itself involves a drug that has toxic—and sometimes fatal—side effects.

  The pre-Columbian inhabitants of South America were plagued by mucosal leish, which they called uta. The grotesque disfigurement of the face terrified the Moche, Inca, and other ancient cultures. They may have considered it a punishment or a curse from the gods. Archaeologists have uncovered burials in Peru and elsewhere of people whose disease was so advanced that they had a caved-in hole where the face used to be—the disease had eaten away everything, including the facial bones. Ancient Peruvian pots so faithfully record the disfigurations that researchers can identify in them the actual clinical stages of the disease, from the early soft-tissue destruction of the nose, to the general destruction of the nose and lips, and finally to the disintegration of the hard palate, nasal septum, upper jaw, and teeth. The Peruvian custom of punishing people by mutilating the nose and lips may have been intended to imitate the facial deformities caused by the disease, perhaps to mimic what they believed was divine retribution.

  Acute fear of the disease may have even driven human settlement patterns in South America. The archaeologist James Kus, a retired professor at California State University, Fresno, believes that the Inca site of Machu Picchu may have been chosen, in part, because of the prevalence of mucosal leish. “The Incas were paranoid about leishmaniasis,” he told me. The sand fly that transmits leish can’t live at higher altitudes, but it is widespread in the lowland areas where the Inca grew coca, a sacred crop. Machu Picchu lies at just the right altitude: too high for leish, but not too high for coca; at Machu Picchu the king and his court could rule from a place of safety and preside over the rituals associated with coca cultivation, without the risk of getting this most dreaded disease.

  When the Spanish conquistadors arrived in South America in the sixteenth century, they were horrified at the facial deformities they saw among native people in the lowlands of the Andes, especially among the coca growers. The Spanish thought they were looking at a form of leprosy and called the disease lepra blanca, “white leprosy.” Over the years, mucosal leish has acquired many nicknames in Latin America: tapir nose, hoarse voice, spongy wound, big canker.

  Mucosal leish didn’t exist in the Old World. But the even deadlier visceral form, the kind that invades the internal organs, had long plagued the Indian subcontinent. It first gained the attention of Western medicine as the British extended their empire into India. Eighteenth-century writers described it as “kala-azar” or “black fever.” Visceral leish easily spreads from person to person via the bite of sand flies, using human beings as its primary reservoir host. It was so deadly and spread so fast that in certain regions of India in the nineteenth century, leishmaniasis would sweep through an area, killing everyone and leaving a landscape of empty villages, entirely bereft of human life.

  The British also noted the cutaneous form of the disease in India and the Near East and gave it various names: Aleppo evil, Jericho button, Delhi boil, Oriental sore. But doctors did not recognize a connection between the two strains until 1901. William Boog Leishman, a doctor from Glasgow who was a general in the British Army, was posted in the town of Dum Dum, near Calcutta, where one of his soldiers fell ill with a fever and a swollen spleen. After the man died, Leishman looked at thin sections of the man’s spleen under the microscope and, using a new staining method, discovered tiny round bodies in the cells—the leishmania parasite. Leishman called it Dum Dum fever. A few weeks after Leisham published his discovery, another British doctor, named Charles Donovan, also stationed in India, independently reported the results of his own research. He, too, had spied the offending parasite, and between the two of them the disease “leishmaniasis” was identified. Leishman got the dubious honor of having the disease named after him, while Donovan was gifted with the species’ name: Leishmania donovani. Doctors figured out in 1911 that it was transmitted by the sand fly, and later they realized that a bewildering number of mammals could be reservoir hosts for the disease, including dogs, cats, rats, mice, gerbils, hamsters, jackals, opossums, foxes, monk seals, and, of course, humans. This astonishingly broad range of host animals makes it one of the most successful diseases on the planet.

  I was still trying to decide whether I should go to NIH or not when the DNA analysis of Dave’s parasites came back. It showed he was infected with a species of leish parasite known as Leishmania braziliensis. This was bad news for Dave and the rest of us, because L. braziliensis causes the third, mucosal variety of the disease, and is considered to be one of the most difficult of all to cure.

  Dr. Nash decided to begin Dave’s treatment immediately. He would use a drug called amphotericin B, administered by slow infusion. Doctors have nicknamed the drug “amphoterrible” because of its nasty side effects. It is considered a last resort, most commonly given to patients with fungal infections of the blood when other drugs have failed; most of these patients are extremely ill with AIDS.

  Dr. Nash would give Dave and the rest of us a formulation of the drug called liposomal amphotericin. In this form, the toxic drug is encapsulated in microscopic spherules made of lipids (fats). This makes the drug safer, reducing some of the most dangerous side effects. But the lipid droplets can cause disturbing side effects of their own.

  The length of treatment depends on how well the patient tolerates the drug and how quickly the ulcer begins to heal. The ideal course, which Dr. Nash had determined over many years of experience, was seven days—long enough to halt the disease but not so long as to harm the patient.

  Shortly after Dave was diagnosed with leish, Tom Weinberg learned from the CDC that he, too, had the disease. Chris Fisher, Mark Adams, and Juan Carlos Fernández went to the NIH and were also diagnosed with it. All were treated except Juan Carlos; Dr. Nash recognized that his immune system appeared to be fighting it off and decided to delay treatment. It was the right decision, and Juan Carlos ended up leish-free without going through the rigors of amphotericin B.

  From the UK we heard that Woody had contracted leish, as had Sully, despite bundling themselves up so scrupulously every evening. Sully was going to be treated at the Royal Centre for Defence Medicine at Birmingham Heartlands Hospital, while Woody was starting treatment at the Hospital for Tropical Diseases in London. Both would get a new drug, miltefosine. Word soon came back from Honduras that many Honduran members of the expedition had also fallen ill with leishmaniasis. These included Oscar Neil, the archaeologist; the commanding officer of the military contingent, Lt. Col. Oseguera; and nine soldiers.

  When the news of our mini-epidemic began to spread among members of the expedition, accompanied by gruesome photos of weeping ulcers, it was hard not to think about the centuries-old legend and its oft-cited “curse of the monkey god.” All those flowers we chopped down! Gallows humor aside, though, many of us were privately aghast at having walked so blithely into that hot zone, and then having congratulated ourselves, prematurely, for emerging from the jungle unscathed. The jokes petered out quickly in the face of this dramatic disease, which had the potential to alter the course of each of our lives. This was deadly serious.

  Because amphotericin is expensive and not available in Honduras, the Honduran members of the expedition were being treated with an older drug, a pentavalent antimonial compound. Antimony, a heavy metal, is directly below arsenic in the periodic table of elements and is similarly poisonous
. This drug kills the parasite while sparing (one hopes) the patient. As bad as ampho B is, this one is worse: Even in the best scenarios it has dreadful side effects. We heard from Virgilio that Oscar, who had been bitten on the right side of his face, had almost died of the treatment and was recovering in seclusion in Mexico. He would have a nasty scar for life; he later grew a beard to cover it up and declined to speak of his experience or do any further work at T1.

  After Dave was diagnosed with mucosal leish, I finally understood that I had to stop procrastinating and get treated. As bad as the treatment sounded, I wasn’t willing to take a chance with the disease itself, or with my face.

  So finally, at the end of May, I called the NIH and set up an appointment for early June to get a biopsy and diagnosis. By this time my bug bite had turned into an oozing crater the size of a quarter, fiery red and disgusting to look at. It didn’t bother me; I’d had no more fevers and I felt fine. Dr. Nash said he doubted my fevers had been caused by the leish anyway; they were, he thought, coincidental viral infections, perhaps opportunistic because my immune system had been shaken up by leish, which hijacks white blood cells.

  As my date approached, I heard that Dave’s treatment with liposomal amphotericin had gone very badly. He had suffered serious kidney damage and Dr. Nash had halted it after only two infusions. He remained hospitalized at the NIH under observation while the doctors debated what to do next.

  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.