Spillover: Animal Infections and the Next Human Pandemic (9 page)

None grew. The cell cultures remained blithely unspotted by viral blooms. And the antibody tests yielded no positive hits either. Once again, Ebola virus had spilled over, caused havoc, and then disappeared without showing itself anywhere but in the sick and dying human victims. It was Zorro, it was the Swamp Fox, it was Jack the Ripper—dangerous, invisible, gone.

This three-month, big-team effort at Kikwit shouldn’t be considered a total failure; even negative results from a well-designed study tend to reduce the universe of possibilities. But it was another hard try ending in frustration. Maybe the Kikwit team had gotten there too late, five months after the charcoal maker fell ill. Maybe the shift from wet season to dry season had caused the reservoir, whatever it is, to migrate or hide or decrease in abundance. Maybe the virus itself had declined to a minimal population, a tenuous remnant, undetectable even within its reservoir during the off season. The Kikwit team couldn’t say. The most notable aspect of their eventual report, apart from its long list of animals that
didn’t
contain Ebola virus, was its clear statement of three key assumptions that had guided their search.

First, they suspected (based on earlier studies) that the reservoir is a mammal. Second, they noted that Ebola virus disease outbreaks in Africa had always been linked to forests. (Even the urban epidemic at Kikwit had begun with that charcoal-maker out amid the woods.) It seemed safe to assume, therefore, that the reservoir is a forest creature. Third, they noted also that Ebola outbreaks had been sporadic in time—with years sometimes passing between one episode and the next. Those gaps implied that infection of humans from the reservoir is a rare occurrence. Rarity of spillover in turn suggested two possibilities: that either the reservoir itself is a rare animal or that it’s an animal only rarely in contact with people.

Beyond that, the Kikwit team couldn’t say. They published their paper in 1999 (among a whole series of reports on Ebola, in a special supplement of the
Journal of Infectious Diseases
), authoritatively documenting a negative conclusion. After twenty-three years, the reservoir still hadn’t been found.

12

“W
e need to know where it is,” Trish Reed had said. She was alluding to the two unanswered questions about Ebola virus and its location in space. The first question is ecological: In what living creature does it hide? That’s the matter of reservoir. The second question is geographical: What’s its distribution across the African landscape? The second may be impossible to answer until the reservoir is identified and
its
distribution traced. In the meantime, the only data reflecting Ebola virus’s whereabouts are the plotted points of human outbreaks on a map.

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 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.” 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 those 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. There is no reason to assume that she will be the last.

13

E
bolavirus 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. 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 species, 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.