Spillover: Animal Infections and the Next Human Pandemic (3 page)

He began his search by going back to the index case—the first equine victim, its history and locale. That was Drama Series, the pregnant mare, fallen ill in the paddock at Cannon Hill. The only clues he had were that this virus was a paramyxovirus and that another Queensland researcher had found a novel paramyxovirus in a rodent some years earlier. So Field established a trapping regime at the paddock, catching every small and medium-sized vertebrate he could—rodents, possums, bandicoots, reptiles, amphibians, birds, the odd feral cat—and drawing blood from each, with a particularly suspicious eye to the rodents. He sent the blood samples to the DPI lab to be screened for antibodies against Hendra.

Screening for antibodies is distinct from isolating virus, just as a footprint is distinct from a shoe. Antibodies are molecules manufactured by the immune system of a host in response to the presence of a biological intruder. They are custom-shaped to merge with and disable that particular virus, or bacterium, or other bug. Their specificity, and the fact that they remain in the bloodstream even after the intruder has been conquered, make them valuable as evidence of present or past infection. That’s the evidence Hume Field was hoping to find. But the rodents from Cannon Hill had no antibodies to Hendra virus. Neither did anything else, leaving him to wonder why. Either he was looking in the wrong place, or in the right place in the wrong way, or at the wrong time. Bad timing might indeed be the problem, he thought. Drama Series had sickened in September, half a year had passed, and here he was searching in March, April, May. He suspected that “there could be some sort of seasonal presence of either the virus or the host” at the Cannon Hill paddock, and that maybe now it was out of season. Screening the cats, dogs, and rats around Rail’s stable yielded no positives either.

Seasonal presence of the virus was one possibility. Coming and going on a shorter time scale was another. Bats, for instance, fed in large numbers at the Cannon Hill paddock by night but returned to their roosts, elsewhere, to sleep out the day. Peter Reid heard a Cannon Hill resident say that, during hours of darkness in the neighborhood, “flying foxes were as thick as the stars in the sky.” Reid had therefore suggested to AAHL that the bats should be looked at, but his suggestion evidently wasn’t passed along. Hume Field and his co-workers on the reservoir hunt remained stumped until the following October, 1995, when an unfortunate event gave them a helpful new lead.

A young cane farmer named Mark Preston, who lived near the town of Mackay, about six hundred miles north of Brisbane, suffered a spate of seizures. His wife got him to a hospital. Preston’s symptoms were especially alarming because they signaled a second health crisis for him in barely more than a year. Back in August 1994, he had endured a mysterious illness—headache, vomiting, stiff neck, then a provisional diagnosis of meningitis, cause unspecified—from which he had recovered. Or had seemingly recovered. Meningitis is a term applicable to any inflammation of the membranes that cover the brain and the spinal cord; it might be caused by a bacterium, a virus, even a reaction to a drug, and it might go away as inexplicably as it appeared. Preston continued to live a robust life on the farm with his wife Margaret, a veterinarian who based her practice there amid the sugar cane and the stud horses.

Did Mark Preston’s seizures now indicate a recurrence of his indeterminate meningitis? Admitted to the hospital, he sunk into severe encephalitis—that is, brain inflammation, cause still unknown. Medication controlled his seizures but the doctors could watch storms of distress flickering on the electroencephalograph. “
He remained deeply unconscious
with persisting fever,” according to a later medical report, “and died 25 days after admission.”

Blood serum taken during Preston’s final illness tested positive for antibodies to Hendra virus. So did his serum from a year earlier, which had been taken during the first episode, stored, and was now tested in retrospect. His immune system had been fighting the thing back then. Postmortem examination of his brain tissue, as well as other tests, confirmed the presence of Hendra. Evidently it had attacked once, subsided, lingered in latent form for a year, and then reared up and killed him. That was scary in a whole new way.

Where had he gotten it? Investigators, working backward to assemble the story, learned that in August 1994 two horses had died on the Preston farm. Mark Preston helped his wife care for them during their sudden, fatal illnesses and assisted her, at least marginally, when she performed the necropsies. Preserved tissue that Margaret Preston had drawn from both horses now also tested positive for Hendra. Despite her own exposure, though, Margaret Preston remained healthy—just as Peter Reid would remain healthy despite his exposure weeks later at Vic Rail’s place. The good health of the two veterinarians raised the question of just how infectious this new virus might be. And the Preston case, at such distance from the first outbreak, caused the experts to wonder—to worry—about how far it might already have spread. Take the mileage from Hendra to Mackay as a radius of potential distribution, draw circles with that radius around the site of each outbreak, and you would circumscribe about 10 million people, nearly half the population of Australia.

How big was the problem? How widely was the virus dispersed? One group of researchers, led by an infectious diseases man named Joseph McCormack, based at the Brisbane hospital where Vic Rail had died, took a broad look. They screened serum from five thousand Queensland horses—every horse they could put a needle in, evidently—and from 298 humans, each of whom had had some level of contact with a Hendra case. None of the horses contained Hendra antibodies, nor did any of the humans. Those negatives, we can assume, brought sighs of relief from the health authorities and deepened the puzzled scowls on the faces of the scientists. “
It seems,
” McCormack’s group concluded, “that very close contact is required for transmission of infection to occur from horses to humans.” But they were whistling in the dark. To say that “very close contact is required” didn’t explain why Margaret Preston had outlived her husband. The reality was this: that very close contact, plus bad luck, plus maybe one or two other factors were necessary for a person to become infected, and nobody knew what the other factors were.

But the Mark Preston case gave Hume Field valuable clues—a second point on the map, a second point in time. Hendra virus in Mackay, August 1994; Hendra virus at the Cannon Hill paddock and in Rail’s stable, September 1994. So Field went up to Mackay and repeated his method, trapping animals, drawing blood, sending serum to be tested for antibodies. And again he found nothing. He also drew samples from injured or otherwise debilitated wildlife of various types, creatures being nurtured in captivity until they could be released (if possible) back to the wild. The people who do such nurturing, a loose network of good-hearted amateurs, are known in Australian parlance as wildlife “carers.” They tend to specialize by zoological category. There are kangaroo carers, bird carers, possum carers, and bat carers. Hume Field knew of them from his years of veterinary practice; he had virtually been one of them, during his student days at the animal refuge. Now he sampled some of the animals in their care.

But damn it: still no trace of Hendra.

In January 1996, with the search for a reservoir host at impasse, Field took part in a brainstorming session of agency officials and researchers, called by his supervisor at DPI. What were they doing wrong? How could they better target their efforts? Where would Hendra strike next? Queensland’s racing industry stood in jeopardy of multi-million-dollar losses, and human lives were at risk. It was an urgent problem of governance and public relations, not just a medical riddle. One useful line of thought was explored at the meeting: biogeography. It seemed obvious that the reservoir host (or hosts), whatever type of animal it was (or they were), must exist both at Mackay and at Cannon Hill—exist there for at least part of each year, anyway, including August and September. This pointed toward animals that were either broadly distributed in Queensland or else
traveled
broadly across the state. The brainstormers (partly guided by genetic evidence suggesting there was no localization of distinct viral strains—that is, the
virus
was moving and mixing) leaned toward the second of those two possibilities: that the reservoir host was quite mobile, an animal capable of traveling hundreds of miles up and down the Queensland coast. That in turn directed suspicion at birds and . . . at bats.

Provisionally, Field and his colleagues dismissed the bird hypothesis, on two counts. First, they were unaware of any other paramyxovirus that spills over from birds into humans. Second, a mammalian reservoir simply seemed more likely, given that the virus infects humans and horses. Similarity of one kind of host animal to another is a significant indicator of the likelihood that a pathogen can make the leap. Bats are mammals, of course. And bats get around. Furthermore, bats famously harbor at least one fearful virus, rabies, although Australia at that time was considered rabies-free. (Many other bat-virus-human connections would be discovered soon afterward, including some in Australia; but at this time, 1996, the link seemed less obvious.) From the meeting, Field took away a new mandate: Look at bats.

Easily said. But catching bats on the wing, or even at their roosting sites, isn’t so simple as trapping rodents or possums in a meadow. The most conspicuous and far-ranging bats native to Queensland are the so-called flying foxes, which belong to four different species within the genus
Pteropus,
each one a magnificent, fruit-eating megabat with a wingspan of three feet or more. Flying foxes customarily roost in mangroves, in paperbark swamps, or high in the limbs of rainforest trees. Special trapping tools and methods would be required. Short of gearing up immediately, Field returned first to the “carer” network. These people already had bats in captivity. At a facility in Rockhampton, up the coast toward Mackay, he found that the wounded animals under care included black flying foxes
(
Pteropus alecto
). Bingo: Blood drawn from a black flying fox had antibodies to Hendra.

But one bingo moment wasn’t sufficient for a scientist so fastidious as Hume Field. That datum proved that black flying foxes could be infected with Hendra, yes, but not necessarily that they were a reservoir—let alone
the
reservoir—from which horses became infected. He and his colleagues kept looking. Within a few weeks, Hendra antibodies turned up in all three other kinds
,
the
grey-headed flying fox, the spectacled flying fox, and the little red flying fox. The DPI team also tested old samples from flying foxes, which had been archived for more than a dozen years. Again, they found telltale molecular tracks of Hendra. This showed that the bat population had been exposed to Hendra virus long before it struck Vic Rail’s horses. And then, in September 1996, two years after the Rail outbreak, a pregnant grey-headed flying fox got herself snagged on a wire fence.

She miscarried twin fetuses and was euthanized. Not only did she test positive for antibodies; she also made possible the first isolation of Hendra virus from a bat. A sample of her uterine fluids yielded live virus, and that virus proved indistinguishable from Hendra as found in horses and humans. It was enough, even within scientific bounds of caution, to identify flying foxes as the “probable” reservoir hosts of Hendra.

The more that Field and his colleagues looked, the more evidence of Hendra they found. After the early bat surveys, about 15 percent of their flying foxes had tested positive for Hendra antibodies. This parameter—the percentage of sampled individuals showing some history of infection, either present or past—is called
seroprevalence
. It constitutes an estimate, based on finite sampling, of what the percentage throughout an entire population might be. As the team continued testing, the seroprevalence rose. At the end of two years, having sampled 1,043 flying foxes, Field and company reported Hendra seroprevalence at 47 percent. In plain words: Nearly half of the big bats flying around eastern Australia were present or former carriers. It almost seemed as though Hendra virus should have been raining down from the sky.

While the scientists published their findings in periodicals such as
Journal of General Virology
and
The Lancet
, some of this stuff got into the newspapers. One headline read:
BAT VIRUS FEAR, RACING INDUSTRY ON ALERT
. The crime-scene tape and the dismembered horses at Rail’s place had been an irresistible starting point for television crews, and their interest continued. A few of those journalistic reports were accurate and sensible, but not all, and none were soothing. People became concerned. The identification of flying foxes as reservoir hosts, plus the high levels of seroprevalence within those bat populations, caused public-image trouble for a group of animals that had a legacy of such trouble already. Approval ratings for bats are never high. Now in Australia they went lower.

One eminent racehorse trainer gave me his view of the matter at a track in Hendra on a sunny Saturday during an interlude between races.
Hendra
virus!
This man exploded at the mention. They shouldn’t
allow
it! “They” were unspecified governmental authorities. They should get
rid
of the bats! Those bats
cause
the disease! They hang upside down and
shit
on themselves! (Can that be true? I wondered. Seemed biologically unlikely.) And they shit on
people
! It’s
backwards
—let the people shit on
them
! What
good
are they?
Get
rid
of them! Why doesn’t that
happen
? Because the
sentimental
Greenies
won’t have it! he groused. We were in the Members Bar, a social sanctum for track professionals, to which I had been admitted in company with Peter Reid. The government should
protect
people! Should protect
vets
, like our friend Peter here! Harrumph, harrumph, and furthermore harrumph! et cetera. This trainer, a legendary figure in Australian racing, was a short, bantam-cocky octogenarian with gray hair combed back in dandy waves. I was a guest in his clubhouse and owed him a little respect—or anyway, a little slack. (In fairness, too, he was speaking not long after still another human victim, a Queensland veterinarian named Dr. Ben Cunneen, had died of Hendra contracted while treating sick horses. The mortal risk to horse people, and the economic risk to the entire Australian racing industry, were undeniably large.) When I showed genial interest in quoting this trainer on the record, he spoke more temperately but the gist was the same.