Because the wives of the Yugoslavian veterinarian and one of the Marburg workers had become ill, there was fear the disease could be passed in the air. Nobody knew how the husbands had originally become infected.
They did know the disease was terrible; the adjective most commonly used to describe it was “agonizing.†Each patient suffered the same excruciating chain of events. After a couple of days of flu-like muscle aches and fever, they began to show classic symptoms of acute viremia (physical responses to a flood of newly made viruses into their bloodstreams): large tender lymph nodes along their throats, inflamed spleens, a marked drop in the number of disease-fighting white blood cells, and a sudden shortage of blood platelets and other factors that are necessary to stop bleeding.
By the sixth day the patients were covered with red rashes that made their skin too sensitive to be touched. Their throats were so raw that they couldn’t eat and had to be fed intravenous fluids, sugars, and vitamins. Within a week, all were suffering acute diarrhea.
By the eighth day, the rashes gave way to a far more painful and alarming reddening of the entire body caused by microscopic blockages throughout the thousands of tiny capillary networks immediately under the surface of the skin. Because the capillaries were blocked, red blood cells backed up, giving the patients a crimson glow. With the red blood cells immobilized, the oxygen those cells normally carried throughout the body was not reaching its destinations. Nerves responded by causing searing pain.
By the tenth day patients were vomiting blood.
At the three-week mark their skin peeled off, as oxygen- and nutrient-starved cells died by the millions. Most painful was the peeling along the patients’ genitals; the testes of some of the men were damaged, shrinking in size.
The doctors noticed a remarkable similarity between their patients’ symptoms and those of the acute phase of hemophilia. In both diseases blood loses its ability to coagulate properly, and some larger blood particles such as platelets get blocked up in peripheral capillaries, while the smaller blood-clotting molecules that normally prevent uncontrolled bleeding simply disappear.
The patients were bleeding to death. As the Frankfurt doctors put it: “Blood is pouring from all apertures.â€2
But this wasn’t hemophilia—it was a contagious disease; one of the Marburg medical team led by Drs. Rudolf Siegert and Gustav Adolf Martini felt justified in labeling it “a new and up to now unknown disease.â€3
By December 1967 seven of the patients had died. Most succumbed within sixteen days of their first symptoms. Some had clearly suffered a brain-related stage of the disease, becoming severely confused, even demented, in the second week of their illness and then falling into deep comas from which they never recovered. Two of the patients’ hearts simply couldn’t bear the burden of pumping so much thick blood, and eventually gave out; they died of massive heart attacks.
For the survivors, the long-term effects of the disease were often serious. Several had permanent damage to their livers, leaving them in a lifelong state of chronic hepatitis. All had lost large amounts of weight. One man became psychotic and never recovered from the psychiatric impact of the ailment. A few of the men were left impotent and with no sex drive.
While physicians in Frankfurt, Marburg, and Belgrade tended to their patients, the World Health Organization assembled a multinational search for the cause of the disease. It seemed obvious the patients had a viral hemorrhagic disease, but attempts to extract the virus based on probes used for other known hemorrhagic diseases (including Machupo and Junin) failed. It seemed this was something altogether new.
All of the original cases in Germany and Yugoslavia involved men who worked with monkeys. Furthermore, investigators discovered, each of the men had handled animals, or the tissue of animals, from the East African nation of Uganda. The investigation narrowed when it was learned the monkeys were all of the same species: Cercopithecus aethiops, a type of vervet monkey common throughout Africa.
The investigators hit pay dirt when they determined that all the monkeys came from three shipments of wild animals transported from Uganda to Belgrade, then on to Marburg and Frankfurt. When the first shipment of animals arrived in Belgrade, 49 of 99 monkeys were dead, and the survivors were placed under quarantine. The Yugoslavian veterinarian who autopsied the dead animals contracted the disease a week later. Shortly after that, his wife, having nursed her husband at home, also developed what would eventually be dubbed Marburg disease. The veterinarian’s autopsies of the dead monkeys revealed that the animals also had suffered massive hemorrhages. Two subsequent shipments of Ugandan monkeys contained large numbers of dead animals.
Martini, Siegert, and their colleagues discovered strange viruses in the blood and tissue of the monkeys. When samples were injected into guinea pigs, the laboratory animals died in a matter of days. But when mice were injected, nothing happened; the mice were somehow able to withstand the virus.
Microscopic studies revealed that the Marburg virus could be found in two different forms. The first looked like a caterpillar, with its long, thin, tubular shape coated with “fuzz.†Inside the tube was RNA (ribonucleic acid), the genetic blueprint of the virus. The “fuzz†along the outside of the virus’s protein tube was a constellation of extruding protein receptors the virus used to gain entry into target cells.
In its more mature and dangerous form, the viral tube was rolled up into a tight round coil that appeared virtually invulnerable to assaults from the cells and antibodies of an ailing creature’s immune system.
In late August, Jordi Casals answered his phone at the Rockefeller Foundation laboratory in New Haven, Connecticut, to hear an operator say, “Now listen carefully, this is Germany talking to you.†The Barcelona-born scientist waited patiently, listening to the roar of the transatlantic telephone cable.
“Dr. Casals?†the caller shouted over the noisy line. “This is Dr. Lehmann-Gruber calling from Marburg, Germany. We need your help.â€
Casals had the largest collection in the world of insect-carried and hemorrhagic viruses, stored under careful security in deep freezers inside the Yale arbovirus laboratory. A few hours after Lehmann-Gruber’s entreaty, a similar call for Casals’s expert assistance came from the Frankfurt group, which told the Rockefeller scientist they were terrified. Both groups, the callers said, had been doing research using monkey kidney cells, and in just three weeks’ time sixteen people had come down with severe hemorrhagic disease and seven had died.
“The people go into shock, they hemorrhage from their noses, anuses, stomachs, mouths,†a very anxious Lehmann-Gruber said. “We are at our wit’s end. We need your help.â€
As the Germans described the frightening symptoms, Casals thought of his friend Karl Johnson’s near-death bout with Machupo. Since the Bolivian incident, Casals and Johnson had become the world’s experts on hemorrhagic diseases, Johnson operating out of Panama and Casals at Yale University, where he ran the Rockefeller Foundation’s arbovirus laboratory.
The Germans desperately wanted to know what was killing their laboratory workers, and they begged Casals to screen patient blood samples against all the viruses in his Rockefeller facility. Casals agreed, with the stipulation that they only send serum samples from patients who had survived the disease. That way, he reasoned, the samples would be free of lethal viruses but would contain antibodies that should react against some virus in his vast Yale collection.
For several weeks Casals and his staff tested the German blood samples against hundreds of viruses, but none gave a positive reaction.
Casals called Lehmann-Gruber, telling him, “It’s not anything we have here in the laboratory. It might be something distinct, something completely new.â€
In September 1967 a WHO team was sent into Uganda to find out where exactly the monkey virus originated. They tested monkey
serum samples taken from wild animals that had been processed for shipments to zoos and research laboratories all over the world. As early as 1961 some monkeys captured near Entebbe and Kidera were infected with Marburg, and the numbers of infected animals, as evidenced by their stored blood samples, increased each year thereafter until late 1967, when a third of some monkey groups carried the virus.
All the actively infected monkeys were of two species: the vervets (African green monkeys) and red-tailed monkeys. Some other animals captured for the study had antibodies to Marburg virus, indicating they had been exposed to the microbe: chimpanzees, baboons, talapoins, and gorillas. It seemed an epidemic had broken out among Ugandan monkeys sometime around 1961, reaching a serious level by 1967. In laboratory studies, it was possible to infect rhesus macaques and a variety of other primates from the Old World (African and Asian animals), but it was not possible to infect New World monkeys or apes (those species from the American continents).
Experimental infection of Old World primates proved, alarmingly, to be 100 percent fatal. Yet it was clear that many, if not most, monkeys that were infected in the wild survived. The paradox was, indeed, puzzling.
In years to come researchers would make many forays into East African wilderness areas in pursuit of solutions to that paradox, as well as a larger one: where did the virus come from? As with most viruses, it was assumed Marburg had a reservoir, a species of some insect or warm-blooded animal in which the virus harmlessly resided and quietly reproduced. The relationship between such viruses and their reservoirs was commensal; neither organism was harmed, over decade after decade of coexistence. But if that reservoir species came in contact with a vulnerable animal, such as a human being, the virus might jump its peaceful ship for the new, highly susceptible vessel, producing an epidemic. When that happened a disease that had existed unnoticed for centuries in other species might suddenly appear “new†when it attacked human beings.
For three years researchers from the United States, Europe, and East Africa scoured Uganda and Kenya in search of a Marburg reservoir. They tested every monkey, ape, rodent, mosquito, tick, hyena, canine, feline, and bovine they could get their hands on. But no reservoir of the virus was ever found.
In the face of this mystery, WHO could not anticipate when or where Marburg might reappear. The agency could only remark on two facets of the German/Yugoslavian outbreak that were responsible for the spread of the virus from monkeys to humans.4
First, said the agency, it was clear that quarantine and export procedures for wild primates were inadequate. All wild animals should be quarantined in the country in which they were captured for a minimum of three weeks, and once quarantine was completed, transport outside the country should be very rapid, preferably by air. The numbers of human beings exposed to the animals during quarantine and transport should be kept at a strict minimum. And during transport, animals, particularly primates, should be separately caged and kept a sufficient distance from one another to ensure there is no clawing or biting during the stressful voyage.
Once animals reached their destination, WHO said, “it is recommended that national veterinary authorities should supervise import and quarantine†for a minimum of six weeks. During the lengthy quarantine period, the animals should, again, be separately caged to avoid spread of disease within the colony, and the numbers of human handlers ought to be minimized. It was considered too obvious to mention that animal caretakers every step of the way should wear appropriate gloves and protective garb, take steps to ensure that they are not bitten by the animals, and remain ever vigilant against allowing animal fluids or tissues to come in contact with any skin cuts or their mouths.5
Regrettably, these instructions would be violated repeatedly in years to come; sometimes with tragic consequences.
Nine years later, in February 1975, two young Australian students on walkabout in Southern Africa would unintentionally serve as “canaries†and prove that Marburg disease hadn’t disappeared from the planet when the 1967 epidemics apparently ceased among vaccine researchers in Europe and in Uganda’s monkey populations.
A twenty-year-old Australian draftsman and his nineteen-year-old girlfriend spent the Southern Hemisphere summer of 1975 hitchhiking around Rhodesia6 and South Africa. Sitting on the roadside outside the Rhodesian Gwaai River town of Wankie one morning, the young man felt a sudden sharp pain in his right leg. Looking down, he saw a red swelling and concluded he’d been bitten.
Six days later the couple was enjoying the Natal beaches near Margate, South Africa, when the young man broke out in a sudden sweat and felt a wave of fatigue that totally sapped him. After four days of escalating muscle pain, exhaustion, fever, and headaches he was admitted to Johannesburg Hospital on February 15, 1975. Four days later, he died, after suffering internal hemorrhaging so severe that the alveolar air sacs of his lungs were filled with blood.
During his four days at Johannesburg Hospital, the Australian was monitored by fifteen doctors and scientists and ten nurses, one of whom, a twenty-year-old nurse, fell ill with the disease nine days after the man died.
Two days after the Australian man’s death, his girlfriend also got the disease. Dr. Margaretha Isaacson, of the South African Institute for Medical Research in Johannesburg, treated the patients with the anticoagulant heparin, saving their lives. No doubt, Isaacson concluded, the vast hemorrhaging seen in the Australian man had been prevented in the other two Marburg victims because heparin stopped mini-clot formation throughout their vascular systems.7
Though the Johannesburg team was convinced the Marburg infection began with the bite on the young man’s leg, they had no idea what sort of creature—rodent, insect, monkey—had attacked him. It was also possible the young man’s mysterious bite had nothing to do with the Marburg infection. Within the ten days before he arrived at Natal, the Australian engaged in several other activities that could have put him in contact with a Marburg-carrying creature. In Rhodesia he slept outdoors on a field that was zebra grazing land; he handled raw meat in Bulawayo; he touched monkeys near the Great Zimbabwe ruins, and he hand-fed monkeys caged in a hotel lobby in Natal.8 The Johannesburg scientists were no closer than their German and Ugandan colleagues had been in 1967 to solving a key mystery: why do such deadly diseases suddenly appear, then just as suddenly disappear?
And so a mystery remained. It began with two teams of German scientists engaged in one of the most optimistic and potentially beneficial pursuits in health care: development of vaccines. It arose from monkey cells, and it ended somewhere in a geographic space so large and varied, spanning thousands of miles from Nairobi to Cape Town, that no one could begin to sift the clues.
At a time when scientists were talking about artificial hearts and advanced brain surgery it seemed almost inconceivable that twenty years later the Marburg mystery would remain utterly opaque.
But it would.
II
Joe McCormick walked briskly down the long emergency ward corridor of the Emilio Ribas Hospital, trying hard to ignore the terrified faces that stared at him from stretchers and chairs. Hospital staff scurried all about him, fighting against time to get acutely ill children and teenagers under treatment before they died.
“We’ve got to do everything we can to avoid panic,†McCormick thought, reiterating the sentence as much for his own edification as for a larger public health concern.
He stepped out into São Paulo’s winter air and stood on the ambulance off-loading dock, watching as another dangerously sick child was transferred from a stretcher to a gurney. Almost in a daze, he glanced at his watch, noted the time, and started counting. In the next thirty minutes, thirteen ambulances arrived, each carrying a Brazilian child or young adult in the grip of meningitis. By day’s end, over 200 patients passed through the emergency doors, and the 1,000-bed hospital was filled well beyond capacity.
It was August 1974, and Brazil’s bu
rgeoning megacity—then boasting a greater metropolitan population of 20 million—was in the throes of an epidemic of meningococcal meningitis, a severe bacterial disease that could kill an untreated human being in less than twenty-four hours. Caused by Neisseria meningitides bacteria, meningococcal infection was spread directly from person to person, carried in the mucoid droplets of a sneeze. Even under the very best of circumstances, meningococcus killed 10 percent of those infected, and these were hardly the best of circumstances. Close to 15 percent of the cases admitted to Emilio Ribas Hospital were dying, and this was the premier treatment facility in São Paulo; death rates in smaller hospitals were as high as 77 percent in infants and 60 percent in adults.9
McCormick was flabbergasted by what he had already seen in his few weeks in São Paulo. He was on loan from the CDC’s Special Pathogens and Bacteria Branch to the Pan American Health Organization (PAHO), with the task of assisting a team of Brazilian doctors in their efforts to stop the epidemic. Though he was relatively new to the CDC, McCormick’s unique background put him in good stead for handling the unfolding Brazilian crisis.
While German public health authorities were panicking about Marburg virus in the summer of 1967, Joe McCormick had been impatiently cooling his heels in a remote northern outpost of Zaire. The former Indiana farm boy had been teaching elementary school in Zaire for two years. He had finished college in 1964, graduating with a stellar record in chemistry. The National Science Foundation offered him a full fellowship for graduate studies in physics, but he had turned it down—for Zaire, and adventure.
Shortly before the first workers fell ill in Marburg, civil war broke out in Zaire, pitting the two-year-old government of Mobutu Sese Seko against Katangan rebel forces led by white mercenaries. Mobutu, who himself came to power through military action, cracked down hard. Among the many measures taken in the summer of 1967 to quell rebellion was mandatory house arrest of all white people residing in Zaire.
The Coming Plague Page 9
