Let’s glance across that map. In 1976 Ebola virus made its debut, as I’ve mentioned, with the dramatic events in Yambuku and the slightly smaller crisis in southwestern Sudan, which was nonetheless large enough to account for 151 deaths. The Sudanese outbreak centered at a town near the Zairian border, five hundred miles northeast of Yambuku. It began among employees of a cotton factory, in the rafters of which roosted bats and on the floor of which skittered rats. The lethality was lower than in Zaire, “only” 53 percent, and laboratory analysis revealed that the Sudanese virus was genetically distinct enough from the virus in Zaire to be classified in a separate species. That species later became known, in careful taxonomic parlance, as Sudan ebolavirus. The official common name is simply Sudan virus, which lacks the frisson of the word “Ebola” but nonetheless denotes a dangerous, blazing killer. The version Karl Johnson and his colleagues had found at Yambuku, originally and still called Ebola virus, belongs to the species Zaire ebolavirus. This may seem confusing, but the accurate, up-to-date labels are important for keeping things straight. Eventually there would be five recognized species.
In 1977 a young girl died of hemorrhagic fever at a mission hospital in a village called Tandala, in northwestern Zaire. A blood sample taken after her death and sent unrefrigerated to the CDC yielded Ebola virus, not in cell cultures but only after inoculating live guinea pigs and then finding the virus replicating in their organs. (These were early days still in the modern field campaign against emerging viruses, and methodology was being extemporized to compensate for difficulties, such as keeping live virus frozen under rough field conditions in the tropics.) Karl Johnson again was part of the laboratory team; this seemed a logical extension of his work on the first outbreak, just a year earlier and two hundred miles east. But the nine-year-old girl, dead in Tandala, was an isolated case. Her family and friends remained uninfected. There was not even a hypothesis as to how she got sick. The later published report, with Johnson again as coauthor, only noted suggestively, in describing the girl’s native area: “Contact with nature is intimate, with villages located in clearings of the dense rain forest or along the rivers of the savannah.”5 Had she touched a dead chimpanzee, breathed rodent urine in a dusty shed, or pressed her lips to the wrong forest flower?
Two years later Sudan virus also resurfaced, infecting a worker at the same cotton factory where it had originally emerged. The worker was hospitalized, upon which he infected another patient, and by the time the virus finished ricocheting through that hospital, twenty-two people were dead. The case fatality rate was again high (65 percent), though lower than for Ebola virus. Sudan virus seemed to be not quite so lethal.
Then another decade passed before filoviruses made their next appearance, in another shape, in an unexpected place: Reston, Virginia.
You know about this if you’ve read The Hot Zone, Richard Preston’s account of a 1989 outbreak of an Ebola-like virus among captive Asian monkeys at a lab-animal quarantine facility in suburban Reston, just across the Potomac from Washington, DC. Filovirus experts express mixed opinions about Preston’s book, but there’s no question that it did more than any journal article or newspaper story to make ebolaviruses infamous and terrifying to the general public. It also led to “a shower of funding,” one expert told me, for virologists “who before didn’t see a dime for their work on these exotic agents!” If this virus could massacre primates in their cages within a nondescript building in a Virginia office park, couldn’t it go anywhere and kill anyone?
The facility in question was known as the Reston Primate Quarantine Unit and owned by a company called Hazelton Research Products, which was a division of Corning. The unfortunate monkeys were long-tailed macaques (Macaca fascicularis), an animal much used in medical research. They had arrived in an air shipment from the Philippines. Evidently they brought their filovirus with them, a lethal stowaway, like smallpox virus making its way through the crew of a sailing ship. Two macaques were dead on arrival, which wasn’t unusual after such a stressful journey; but over the following weeks, within the building, many more died, which was unusual. Eventually the situation triggered alarm and the infective agent was recognized as an ebolavirus—some sort of ebolavirus, as yet unspecified. A team from USAMRIID came in, like a SWAT team in hazmat suits, to kill all the remaining macaques. Then they sealed the Reston Primate Quarantine Unit and sterilized it with formaldehyde gas. You can read Preston for the chilling details. There was great anxiety among the experts because this ebolavirus seemed to be traveling from monkey to monkey in airborne droplets; a leak from the building might therefore send it wafting out into Washington-area traffic. Was it lethal to humans as well as to macaques? Several staff members of the Quarantine Unit eventually tested positive for antibodies but—sigh of relief—those people showed no symptoms. Laboratory work revealed that the virus was similar to Ebola virus yet, like Sudan virus, different enough to be classified in a new species. It came to be known as Reston virus.
Notwithstanding that name, Reston virus seems to be native to the Philippines, not to suburban Virginia. Subsequent investigation of monkey-export houses near Manila, on the island of Luzon, found a sizable die-off of animals, most of which were infected with Reston virus, plus twelve people with antibodies to the virus. But none of the dozen Filipinos got sick. So the good news about Reston virus, derived both from the 1989 US scare and from retrospective research on Luzon, is that it doesn’t seem to cause illness in humans, only in monkeys. The bad news is that no one understands why.
Apart from Reston virus, ebolaviruses in the wild remain an African phenomenon. But the next emergence, in November 1992, added yet another point to the African map. Chimpanzees began dying at a forest refuge in Côte d’Ivoire, West Africa. The refuge, Taï National Park, lying near Côte d’Ivoire’s border with Liberia, encompassed one of the last remaining areas of primary rainforest in that part of Africa. It harbored a rich diversity of animals, including several thousand chimpanzees.
One community of those chimps had been followed and studied for thirteen years by a Swiss biologist named Christophe Boesch. During the 1992 episode, Boesch and his colleagues noticed a sudden drop in the population—some chimps died, others disappeared—but the scientists didn’t detect a cause. Then, in late 1994, eight more carcasses turned up over a short period of time, and again other animals went missing. Two of the chimp bodies, only moderately decayed, were cut open and examined by researchers at Taï. One of them proved to be teeming with an Ebola-like agent, though that wasn’t apparent at the time. During the necropsy, a thirty-four-year-old female Swiss graduate student, wearing gloves but no gown, no mask, became infected. Infected how? There wasn’t any obvious moment of fateful exposure, no slip of the scalpel, no needlestick mishap. Probably she got chimp blood onto a broken patch of skin—a small scratch?—or caught a gentle splash of droplets in the face. Eight days later, the woman started shivering.
She took a dose of malaria medicine. That didn’t help. She was moved to a clinic in Abidjan, Côte d’Ivoire’s capital, and there treated again for malaria. Her fever continued. On day 5 came vomiting and diarrhea, plus a rash that spread over her whole body. On day 7 she was carried aboard an ambulance jet and flown to Switzerland. Now she was wearing a mask, and so were the doctor and the nurse in attendance. But no one knew what ailed her. Dengue fever, hantavirus infection, and typhoid were being considered, and malaria still hadn’t been ruled out. (Ebola wasn’t at the top of the list because it had never been seen in Côte d’Ivoire.) In Switzerland, hospitalized within a double-door isolation room with negative air pressure, she was tested for a whole menu of nasty things, including Lassa fever, Crimean-Congo hemorrhagic fever, chikungunya, yellow fever, Marburg virus disease, and now, yes, Ebola virus disease. The last of those possibilities was investigated using three kinds of assays, each one specific: for Ebola virus, for Sudan virus, for Reston virus. No positive results. The antibodies in those assays didn’t recognize the virus, whatever it was, in
her blood.
The laboratory sleuths persisted, designing a fourth assay that was more generalized—comprehensive for the whole group of ebolaviruses. Applied to her serum, that one glowed, a positive, announcing the presence of antibodies to an ebolavirus of some sort. So the Swiss woman was the world’s first identified victim of what became known as Taï Forest virus. The chimpanzee she had necropsied, its tissues tested later, was the second victim, recognized posthumously.
Unlike the chimp, she survived. After another week, she left the hospital. She had lost thirteen pounds and her hair later fell out, but otherwise she was okay. Besides being the initial case of Taï Forest virus infection, the Swiss woman holds one other distinction: She is the first person known to have carried an ebolavirus infection off the African continent. Events in 2014 have shown that she wasn’t the last.
6
EBOLAVIRUS SPILLOVERS CONTINUED throughout the 1990s and into the twenty-first century, sporadic and scattered enough to make field research difficult, frequent enough to keep some scientists focused and some public health officials worried. In 1995, soon after the Côte d’Ivoire episode, it was Ebola virus in Kikwit, about which you’ve read. Six months after that outbreak, as you’ll also recall, the new one began at Mayibout 2. What I haven’t yet mentioned about Mayibout 2 is that, though the village lies in Gabon, the virus was Ebola as known originally from Zaire, which seems to be the most broadly distributed of the group. And again at the timber camp near Booué, Gabon, it was Ebola virus.
Also that year, 1996, Reston virus reentered the United States by way of another shipment of Philippine macaques. Sent from the same export house near Manila that had shipped the original sick monkeys to Reston, Virginia, these went to a commercial quarantine facility in Alice, Texas, near Corpus Christi. One animal died and, after it tested positive for Reston virus, forty-nine others housed in the same room were “euthanized” as a precaution. (Most of those, tested posthumously, were negative.) Ten employees who had helped unload and handle the monkeys were also screened for infection, and they also tested negative, but none of them were euthanized.
Uganda became the next known locus of the virus in Africa, with an outbreak of Sudan virus that began near the northern town of Gulu in August 2000. Northern Uganda shares a border with what in those days was southern Sudan, and it wasn’t surprising that Sudan virus might cross or straddle that border. Cross it how, straddle it how? By way of the individual movements or the collective distribution of the reservoir host, identity unknown. This is a pointed example of why solving the reservoir mystery is important: If you know which animal harbors a certain virus and where that animal lives—and conversely, where it doesn’t live—you know where the virus may next spill over, and where it probably won’t. That provides some basis for focusing your vigilance. If the reservoir is a rodent that lives in the forests of southwestern Sudan but not in the deserts of Niger, the goat herders of Niger can relax. They have other things to worry about.
In Uganda, unfortunately, the 2000 spillover led to an epidemic of Sudan virus infections that spread from village to village, from hospital to hospital, from the north of the country to the southwest, killing 224 people.
The case fatality rate was again “only” 53 percent, exactly what it had been in the first Sudanese outbreak, back in 1976. This precise coincidence seemed to reflect a significant difference in virulence between Sudan and Ebola viruses. Their difference, in turn, might reflect different evolutionary adjustments to humans as a secondary host (though random happenstance is also a possible explanation). Many factors contribute to the case fatality rate during an outbreak, including diet, economic conditions, public health in general, and the medical care available in the location where an outbreak occurs. It’s hard to isolate the inherent ferocity of a virus from those contextual factors. What can be said, though, is that Ebola virus appears to be the meanest of the four ebolaviruses you’ve heard about, as gauged by its effect on human populations. Taï Forest virus can’t reliably be placed on that spectrum at all, not yet—for lack of evidence. Having infected just one known human (or possibly two, counting an unconfirmed later case) and killed none, Taï Forest virus may be less prone to spillover. It may or may not be less lethal; one case, like one roll of the dice, proves nothing about what’s likely to emerge as numbers grow larger. Then again, Taï Forest virus might also be spilling more frequently but inconsequentially—infecting people yet not causing notable illness. No one has screened the populace of Côte d’Ivoire to exclude that possibility.
The role of evolution in making Taï Forest virus (or any virus) less virulent in humans is a complicated matter, not easily deduced from simple comparison of case fatality rates. Sheer lethality may be irrelevant to the virus’s reproductive success and long-term survival, the measures by which evolution keeps score. Remember, the human body isn’t the primary habitat of ebolaviruses. The reservoir host is.
Like other zoonotic viruses, ebolaviruses have probably adapted to living tranquilly within their reservoir (or reservoirs), replicating steadily but not abundantly and causing little or no trouble. Spilling over into humans, they encounter a new environment, a new set of circumstances, often causing fatal devastation. And one human can infect another, through direct contact with bodily fluids. But the chain of ebolavirus infection, at least so far, has never continued through many thousands of successive cases, great distances, or long stretches of time. Some scientists use the term “dead-end host” to describe humanity’s role in the lives and adventures of ebolaviruses. What the term implies is this: Outbreaks have been contained and terminated; in each situation the virus has come to a dead end, leaving no offspring. Not the virus in toto throughout its range, of course, but that lineage of virus, the one that has spilled over, betting everything on this gambit—it’s gone, kaput. It’s an evolutionary loser. It hasn’t caught hold to become an endemic disease within human populations. It hasn’t caused a huge epidemic. Ebolaviruses, judged by experience so far, fit that pattern. Careful medical procedures (such as barrier nursing by way of isolation wards, examination gloves, gowns, masks, and disposable needles and syringes) usually stop them. Sometimes simpler methods can bring a local spillover to a dead end too. This has probably happened more times than we’ll ever know. Advisory: If your husband catches an ebolavirus, give him food and water and love and maybe prayers but keep your distance, wait patiently, hope for the best—and, if he dies, don’t clean out his bowels by hand. Better to step back, blow a kiss, and burn the hut.
This business about dead-end hosts is the conventional wisdom. It applies to the ordinary course of events. But there’s another perspective to consider. Zoonoses by definition involve events beyond the ordinary, and the scope of their consequences can be extraordinary too. Every spillover is like a sweepstakes ticket, bought by the pathogen, for the prize of a new and more grandiose existence. It’s a long-shot chance to transcend the dead end. To go where it hasn’t gone and be what it hasn’t been. Sometimes the bettor wins big.
7
IN LATE 2007 a fifth ebolavirus emerged, this one in western Uganda.
On November 5, 2007, the Ugandan Ministry of Health received a report of twenty mysterious deaths in Bundibugyo, a remote district along the mountainous border with the Democratic Republic of the Congo (the new name, as of 1997, for what had been Zaire). An acute infection of some unknown sort had killed those twenty people, abruptly, and put others at risk. Was it a rickettsial bacterium, such as the one that causes typhus? An ebolavirus was another possibility, but considered less likely at first, because few of the patients hemorrhaged. Blood samples were gathered quickly, flown to the CDC in Atlanta, and tested there, using both a generalized assay that might detect any form of ebolavirus and specific assays for each of the known four. Although the specific tests were all negative, the general test rang up some positives. So on November 28, the CDC informed Ugandan officials: It’s an ebolavirus, all right, but not one we’ve ever seen.
&
nbsp; Further laboratory work established that this new virus was at least 32 percent different genetically from any of the other four. It became Bundibugyo virus. Soon a CDC field team arrived in Uganda to help respond to the outbreak. As usual in such situations, their efforts along with those of the national health authorities involved three tasks: caring for patients, trying to prevent further spread, and investigating the nature of the disease. The eventual tally was 116 people infected, of whom 39 died.
Also as usual, the scientific team later published a journal article, in this case announcing the discovery of a new ebolavirus. First author on the paper was Jonathan S. Towner, a molecular virologist at the CDC with field experience in the search for reservoirs. Besides guiding the lab work, he went to Uganda and did a stint with the response team. The Towner paper contained a very interesting statement, as an aside, concerning the five ebolaviruses: “Viruses of each species have genomes that are at least 30–40% divergent from one another, a level of diversity that presumably reflects differences in the ecologic niche they occupy and in their evolutionary history.”6 Towner and company suggested that some of the crucial differences between one ebolavirus and another—including the differences in lethality—might be related to where and how they live, where and how they have lived, within their reservoir hosts.
The events in Bundibugyo left many Ugandans uneasy. And they were entitled to their uneasiness: Uganda now held a sorry distinction as the only country on Earth that had suffered outbreaks of two different ebolaviruses (Sudan virus at Gulu in 2000, Bundibugyo virus in 2007), as well as outbreaks of both Ebola virus disease and Marburg virus disease, caused by another filovirus, within a single year. (The creepy circumstances of the Marburg spillover, at a gold mine called Kitaka in June 2007, are part of a story I’ll come to in its turn.) Given such national ill fortune, it’s not surprising that there were rumors, stories, and anxieties circulating among Ugandans, in late 2007, that made tracing genuine ebolavirus leads all the more difficult.
Ebola: The Natural and Human History of a Deadly Virus Page 4
