Spillover: Animal Infections and the Next Human Pandemic (45 page)

After twelve days, she left the hospital, still weak and anemic, still undiagnosed. In March she saw Norman Fujita on a follow-up visit and he had her serum tested again for Marburg. Again, negative. Three more months passed and Michelle, now gray-haired, lacking her old energy, suffering abdominal pain, unable to focus, got an email from a knowing friend—a journalist she and Rick had met during the Uganda trip—who had just seen a news article about which he thought Michelle should know. In the Netherlands, a woman had died of Marburg after a Uganda vacation during which she had visited a cave full of bats.

Barnes spent the next twenty-four hours googling up every article on the case she could find. By a small-world coincidence, she had lived in the Netherlands for three years herself, during the 1990s, so she could read the coverage in Dutch as well as in English. Early the following Monday morning, she was at Dr. Fujita’s door. “I’m an emergency, I need to speak with you,” she said. Fujita welcomed her in and listened to the new information. Beyond his polite demeanor, she felt, he must be rolling his eyes and thinking,
Great, another person who diagnoses herself from the Internet.
But he agreed to test her a third time for Marburg. That sample went to the CDC, as had the earlier ones, and again tested negative; but this time a lab technician, aware that the patient had visited a cave inhabited by Marburg-infected bats, cross-checked the third sample, and then the first sample also, using a more sensitive and specific assay.
Boing
.

The new results went to Fujita, who called Barnes with some left-handed congratulations: “You’re now an honorary infectious disease doctor. You’ve self-diagnosed, and the Marburg test came back positive.”

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N
ews of the Joosten case also reverberated at the CDC. Soon afterward, in August 2008, another team was dispatched to Uganda, this time including the veterinary microbiologist Tom Ksiazek, a veteran of field responses against zoonotic outbreaks, as well as Towner and Amman. Bob Swanepoel and Alan Kemp were again mustered from South Africa. “We got the call, ‘Go investigate,’ ” Amman told me. Their mission now was to sample bats at Python Cave, where this Dutch woman (unnamed in the epidemiological traffic) had become infected. Her death, her case history, implied a change in the potential scope of the situation. That local Ugandans were dying of Marburg was a severe and sufficient concern—sufficient to bring a response team in haste from Atlanta and Johannesburg. But if tourists too were involved, tripping in and out of some lovely python-infested Marburg repository, in Tevas and hiking boots, blithe, unprotected, and then boarding their return flights to other continents, the place was not just a peril for Ugandan miners and their families. It was also an international threat.

The team converged at Entebbe and drove southwest. They walked the same trail that Joosten and Barnes and their husbands had walked, to the same opening amid the forest vegetation. Then, unlike the others, they donned their Tyvek pajamas, their rubber boots, their respirators, and their goggles. This time, with cobras in mind, they added snake chaps. Then they went in. Bats were everywhere overhead; guano was everywhere underfoot. In fact, the rain of guano seemed to come so continuously, Amman told me, that if you left something on the floor it would be covered within days. The pythons were indolent and shy, as well-fed snakes tend to be. One of them, by Amman’s estimate, stretched about twenty feet long. The black forest cobras (yes, more of them here too) kept to the deeper recesses, away from heavy traffic. Towner was gazing at a python when Amman noticed something glittery on the floor.

At first glance it looked like a bleached vertebra, lying in the excremental glop. Amman picked the thing up.

It wasn’t a vertebra. It was a string of aluminum beads with a number attached. More specifically, it was one of the beaded collars that he and Towner had placed on captured bats at Kitaka Cave, the
other
Marburg cave, three months earlier and thirty miles away. The code tag spoke one simple fact: Here was collar K-31, from the thirty-first animal they had released. “And of course, I just lost my mind,” Amman told me. “I was, ‘Yeah!’ and jumping around. Jon and I were so excited.” Amman’s insane jubilance was in fact just the sane, giddy thrill that a scientist feels when two small bits of hard-won data click together and yield an epiphany. Towner got it and shared it. Picture two guys in a dark stone room, wearing headlamps, high-fiving in nitrile gloves.

Retrieving the collar at Python Cave vindicated, in a stroke, their mark-recapture study. “It confirmed my suspicions that these bats are moving,” Amman said—and moving not only through the forest but from one roosting site to another. Travel of individual bats (such as K-31) between far-flung roosts (such as Kitaka and Python) implied circumstances whereby Marburg virus might ultimately be transmitted all across Africa, from one bat encampment to another. It suggested opportunities for infecting or reinfecting bat populations in sequence, like a string of blinking Christmas lights. It voided the comforting assumption that this virus is strictly localized. And it highlighted the complementary question: Why don’t outbreaks of Marburg virus disease happen more often?

Marburg is only one instance to which that question applies. Why not more Hendra? Why not more Nipah? Why not more Ebola? Why not more SARS? If bats are so abundant and diverse and mobile, and zoonotic viruses so common within them, why don’t those viruses spill into humans and take hold more frequently? Is there some mystical umbrella that protects us? Or is it fool’s luck?

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T
he ecological dynamics of the virus itself may be part of the reason that such diseases aren’t constantly raining down. Yes, viruses
do
have ecological dynamics, just as do creatures that are more unambiguously alive. What I mean is: They’re interconnected with other organisms at the scale of landscapes, not just at the scale of individual hosts and cells. A virus has geographical distribution. A virus can go extinct. The abundance, survival, and range of a virus all depend upon other organisms and what those do. That’s viral ecology. In the case of Hendra, to take another instance, the changing ecology of the virus may partly account for its emergence as a cause of human disease.

This line of thought has been explored by an Australian scientist named Raina Plowright. Trained first as a veterinarian, Plowright worked on domestic animals and wildlife in New South Wales and overseas—Britain, Africa, Antarctica—before fetching up at the University of California, Davis, to do a master’s degree in epidemiology and then a doctorate in the ecology of infectious diseases. She is one of this new breed of cross-trained disease specialists I’ve mentioned, veterinarian-ecologists who recognize the intimate connectedness of human health, wildlife health, livestock health, and the habitats we all share. For her doctoral fieldwork, Plowright returned to Australia to investigate the dynamics of Hendra virus within one of its reservoir hosts: the little red flying fox. She did some of her trapping and sampling in the Northern Territory, south of Darwin, amid the eucalyptus and melaleuca forests in and around Litchfield National Park. That’s where I spoke with her, during one idle morning in 2006, as Cyclone Larry swept across northern Australia, drenching the land and raising the rivers and creeks. We had some time to kill before she went out once again and tried to catch bats amid the monsoonal flooding.

An interesting thing about Hendra, Plowright told me, is that it’s one of four new viruses that emerged around the same time from this single group of bats, the pteropids
.
Soon after Hendra virus made its debut north of Brisbane, in 1994, there was Australian bat lyssavirus, appearing at two other sites along the Queensland coast, in 1996; then Menangle virus, emerging near Sydney, in 1997; and then Nipah virus, up in Malaysia, in September 1998. “For four viruses to emerge from one host genus within a short period of time is unprecedented,” she said. “So we feel there’s been some change in the ecology of
Pteropus
species that could precipitate disease emergence.” Hume Field had helped identify such contributing factors in the case of Nipah virus among the pig farms of Malaysia. Now, eight years later, with Field on her committee of dissertation advisers, Plowright was looking for similar factors in the matter of Hendra. Changes in habitat, she knew, had affected population size, distributional patterns, and migratory behavior of Hendra reservoir hosts—not just the little red flying fox but also its congenerics, the black flying fox, the grey-headed, and the spectacled. Her task was to investigate how those changes had affected in turn the distribution, prevalence, and spillover likelihood of the virus.

Plowright’s project, like much work in ecology these days, entailed a combination of data-gathering from the field and mathematical modeling by computer. The basic conceptual framework, she explained, “was developed by two guys in the 1920s, Kermack and McKendrick.” She meant the
SIR
model (susceptible-infected-recovered), which I described earlier. Having alluded to the intellectual heritage, she began talking about susceptible individuals, infected individuals, and recovered individuals in a given bat population. If the population is isolated and insufficiently large, then the virus will move through it, infecting the susceptibles and leaving them recovered (and immune to reinfection), until there are virtually no susceptibles left. Then it will die out, just as measles dies out in an isolated human village. Eventually the virus will return, brought back to that population by a wayward, infected bat. This represents the same blinking-Christmas-light pattern that I invoked with regard to Marburg. The ecologists call it a
metapopulation
: a population of populations. The virus avoids extinction by infecting one relatively isolated population of bats after another. It dies out here, it arrives and infects there; it may not be permanently present in any one population but it’s always somewhere. The lights blink off/on in their turns, never all lit, never all dark. If the bat populations are separated by distances great enough that those distances are seldom crossed, then the rate of reinfection is slow. The lights blink off and on languidly.

Now imagine one such bat population within the metapopulation. It has progressed through the
SIR
sequence, every individual infected, every one recovered, and the virus is gone. But not gone forever. As years pass, as the birth of new bats and the death of old ones raise back the proportion of susceptibles, the population regains its collective vulnerability to the virus. Greater isolation means greater elapsed time before the virus returns; greater elapsed time yields more newborn susceptibles; more susceptibles mean a richer potential for explosive infection. “So when you do introduce the virus again,” Plowright said, describing the godlike role of the modeler, “you get a much bigger outbreak.” This is where the Christmas-light metaphor fails to serve, because one light suddenly glows like a supernova among ordinary stars.

Plowright of course was working with numbers, not analogies. But her numbers reflected roughly this scenario. The relevance of such modeling to the facts on the ground is that Australian populations of flying foxes
have
become more isolated in recent decades. “The east coast of Australia used to be one big contiguous forest,” she told me, “and so you had bat populations pretty evenly dispersed along the coastline.” Their roosting aggregations, in the old days, were relatively mobile. Their food resources—mainly nectar and fruit—were diverse, seasonally variable, and scattered patchily throughout the forest. Each group of bats, comprising maybe a few hundred or a few thousand individuals, would fly out to a feeding site at night, return at daylight, and also migrate seasonally to put themselves closer to concentrations of food. With all the coming and going, individual bats would sometimes transfer from one group to another, carrying Hendra virus with them if they happened to be infected. There was a continual mixing and a continual reinfection of the smallish groups. This seems to have been the situation—for the little red flying fox, for the other flying foxes, and for Hendra virus—from time immemorial. Then things changed.

Habitat alteration was an ancient tradition in Australia, in the form of burning by Aboriginal people, but in recent decades land clearance has become a more drastic and mechanized trend, with less-reversible results, especially in Queensland. Vast areas of old forest have been cut, or chained down with bulldozers, to make way for cattle ranching and urban sprawl. People have planted orchards, established urban parks, landscaped their yards with blossoming trees, and created other unintended enticements amid the cities and suburbs. “So bats have decided that, as their native habitat is disappearing, as climate is becoming more variable, and their food source is becoming less diverse, it’s easier to live in an urban area.” They gather now in larger aggregations, traveling shorter distances to feed, living at closer proximity to humans (and to the horses that humans keep). Flying foxes in Sydney, flying foxes in Melbourne, flying foxes in Cairns. Flying foxes in the Moreton Bay fig trees shading a paddock on the north side of Brisbane.

I saw where Plowright was going and tried to frame the last bit in my own mind. So those large aggregations—comprising bats that are more sedentary, more urban, less needful of flying long distances in search of wild food—tend to reinfect one another less frequently? And in the interim they accumulate more susceptible individuals? So when the virus does arrive, the spread of new infections is more sudden and intense? The virus is more prevalent and abundant?

“Exactly. That’s it,” she said.

“And then a great likelihood of spillover into another species?” I wanted to leap toward that easy epiphany but Plowright, with many bats yet to catch, many data to assemble, many model parameters to explore, held me back. Five years after our conversation, with the PhD finished, now a respected voice on Hendra herself, she would present her work and ideas in an august journal, the
Proceedings of the Royal Society
. But for the moment, amid the rains and high waters of the Northern Territory, she spoke provisionally.