Spillover
Page 3
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.
Among the “sentimental Greenies,” he would have included bat carers. But even some of those softhearted activists, the carers, grew concerned as evidence piled up. They had two worries, uneasily counterbalanced: that the virus would make bats even more unpopular, leading to calls (like the trainer’s) for bat extermination, and that they themselves might become infected in the course of their well-meaning work. The second was a new sort of anxiety. It must have caused some reexamination of commitment. They were bat lovers, after all, not virus lovers. Does a virus constitute wildlife? Not in most people’s minds. Several such carers asked to be screened for antibodies, which opened doors for a broad survey, quickly organized and led by a young epidemiologist from the University of Queensland named Linda Selvey.
Selvey tapped into the wildlife-carer networks in southeastern Australia, eventually finding 128 bat carers willing or eager to be tested. She and her field team drew the blood and asked each participant to complete a questionnaire. The questionnaires revealed that many of these people had had prolonged and close contact with flying foxes—feeding them, handling them, not infrequently getting scratched or
nipped. One carer had been bitten deeply on the hand by a Hendra-positive bat. The most unexpected finding of Selvey’s survey was the percentage of those 128 carers who tested positive for antibodies: zero. Despite months and years of nurturing, despite scratches and bites and cuddling and drool and blood, not one person showed immunological evidence of having been infected with Hendra virus.
Selvey’s report appeared in October 1996. She was a grad student at the time. Later she became head of the Communicable Diseases Branch of Queensland Health. Still later, as we sat over coffee in a noisy Brisbane café, I asked her: Who are these bat carers?
“I don’t know how to describe them,” Selvey answered. “People with a passion for animals, I guess.” Both women and men? “Predominantly women,” she said, speculating gently that women without kids might have more time and more desire for such surrogacy. Generally they do the caring in their own homes, equipped with a sizable, comfortable cage where the bats can roost when not being handled. It seemed mystifying to me that such intimate bat-human relations, combined with such a high level of bat seroprevalence, had yielded not a single case of human infection to be detected by Selvey’s study. Not a single antibody-positive person out of 128 carers. What did that tell you, I asked her, about the nature of this virus?
“That it needed some sort of amplifier,” she said. She was alluding to the horse.
5
Let’s think about foot-and-mouth disease for a moment. Everybody has heard of it. Everybody has seen Hud. Most people aren’t aware that, at least tenuously, it’s a zoonosis. The virus that causes foot-and-mouth disease (FMD) belongs to the picornaviruses, the same group that includes poliovirus and some viruses similar to those that cause the common cold. But infection with FMD virus is a rare misfortune in humans, seldom causing worse than a rash on the hands, the feet, or the mouth lining. More frequently and consequentially, it afflicts cloven-hoofed domestic animals such as cattle, sheep, goats, and pigs. (Cloven-hoofed wildlife such as deer, elk, and antelope are also susceptible.) The main clinical signs are fever, lameness, and vesicles (little blisters) in the mouth, on the snout, on the feet. In a lactating female, the teats sometimes become blistered and then, as the blisters break, ulcerated. Bad for the mother, bad for the calf. Lethality from FMD is relatively low but the morbidity (incidence of the disease within a population) tends to be high, meaning that the disease is very contagious, making livestock ill, putting them off their feed, and causing losses of productivity that, in big-volume operations with narrow profit margins, are considered disastrous. Because of such losses, plus the swiftness of contagion, it’s often treated as a terminal condition in commercial terms: Infected herds are slaughtered to prevent the virus from getting around. Nobody wants to buy stock that might be carriers, and the export trade drops to zilch. Cows, sheep, and pigs become worthless—less than worthless, an expensive liability. “Economically, it is the most important disease of animals in the world,” according to one authority, who reports that “an FMD outbreak in the US could cost $27 billion in lost trade and markets.” The virus spreads through direct contact, and in feces, and in milk, and is even capable of transmission by aerosol. It can travel from one farm to another on a humid breeze.
Impacts of FMD differ from one kind of animal to another. Sheep tend to carry the infection without showing symptoms. Cattle suffer openly and pass the virus to one another by direct contact (say, muzzle to muzzle) or vertically (cow to calf) by suckling. Pigs are special: They excrete far more of the virus than other livestock, and over a longer period of time, broadcasting it prodigiously in their respiratory exhalations. They sneeze it, they chuff it, they oink it, they wheeze it and burp it and cough it into the air. One experimental study found that pig breath carried thirty times as much FMD virus as the breath of an infected cow or sheep, and that once airborne it could spread for miles. That’s why pigs are considered an amplifier host of this virus.
An amplifier host is a creature in which a virus or other pathogen replicates—and from which it spews—with extraordinary abundance. Some aspect of the host’s physiology, or its immune system, or its particular history of interaction with the bug, or who knows what, accounts for this especially hospitable role. The amplifier host becomes an intermediate link between a reservoir host and some other unfortunate animal, some other sort of victim—a victim requiring higher doses or closer contact before the infection can take hold. You can understand this in terms of thresholds. The amplifier host has a relatively low threshold for becoming infected, yet it produces a vast output of virus, vast enough to overcome the higher threshold in another animal.
Not every zoonotic pathogen requires an amplifier host for successful infection of humans, but some evidently do. Which ones, and how does the process work? The disease scientists are exploring those questions, among many others. Meanwhile, the concept is a hypothetical tool. Linda Selvey didn’t mention the FMD paradigm when she used the word “amplifier” in our conversation about Hendra virus, but I knew what she meant.
Still . . . why horses? Why not kangaroos or wombats or koalas or potoroos? If the horse fills that amplifying role, one obvious fact deserves fresh attention: Horses aren’t native to Australia. They are exotic, first brought there by European settlers barely more than two centuries ago. Hendra is probably an old virus, according to the runic evidence of its genome, as read by molecular evolutionists. Distantly diverged from its morbillivirus cousins, it may have abided unobtrusively in Australia for a very long time. Bats too are an ancient part of the native fauna; the fossil record in Queensland shows that small bats have been there for at least 55 million years, and flying foxes may have evolved in the region during the early Miocene, about 20 million years ago. Human presence is more recent, dating back only tens of millennia. More precisely, humans have inhabited Australia since the pioneering ancestors of Australian aboriginal peoples first made their way, island hopping daringly in simple wooden boats, from southeastern Asia by way of the South China Sea and the Lesser Sunda Islands to the northwestern coast of the island continent. That was at least forty thousand years ago, possibly much earlier. So three of the four principals in this complex interaction—flying foxes, Hendra virus, and people—have probably coexisted in Australia since the Pleistocene era. Horses arrived in January 1788.
It was a small change on the landscape, compared to all that would follow. Those earliest horses came aboard ships of the First Fleet, under command of Captain Arthur Phillip, who had sailed out from Britain to establish a convict colony in New South Wales. After five months of navigating the Atlantic, Phillip stopped at a Dutch settlement near the Cape of Good Hope to take on provisions and livestock before continuing eastward from Africa. He rounded Van Diemen’s Land (now Tasmania) and sailed north along mainland Australia’s east coast. Captain James Cook had already come and gone, “discovering” the place, but Phillip’s group would be the first European settlers. At a spot near what is now Sydney, within the fine natural harbor there, his penal arks put ashore 736 convicts, 74 pigs, 29 sheep, 19 goats, 5 rabbits, and 9 horses. The horses included two stallions, four mares, and three foals. Until that day there was no record, either fossil or historic, of members of the genus Equus in Australia. Nor were there any oral traditions (none shared with the world so far, anyway) of Hendra virus outbreaks among aboriginal Australians.
As of January 27, 1788, then, the elements were almost certainly gathered in place—the virus, the reservoir hosts, the amplifier host, plus susceptible humans. And now another riddle presents itself. From the horses of Captain Arthur Phillip to the horses of Vic Rail is a gap of 206 years. Why did the virus wait so long to emerge? Or had it indeed emerged previously, maybe often, and never been recognized for what it is? How many past cases of Hendra, over two centuries or more, have been misdiagnosed as snakebite?
Answer from the scientists: We don’t know but we’re working on it.
6
Hendra virus in 1994 was just one thump in a drumbeat o
f bad news. The drumbeat has been sounding ever more loudly, more insistently, more rapidly over the past fifty years. When and where did it start, this modern era of emerging zoonotic diseases?
To choose one point is a little artificial, but a good candidate would be the emergence of Machupo virus among Bolivian villagers between 1959 and 1963. Machupo wasn’t called Machupo at the start, of course, nor even recognized as a virus. Machupo is the name of a small river draining the northeastern Bolivian lowlands. The first recorded case of the disease came and went, almost unnoticed, as a bad but nonfatal fever afflicting a local farmer. This was during the wet season of 1959. More such illnesses, and worse, occurred in the same region over the following three years. Symptoms included fever and chills, nausea and vomiting, body aches, nosebleeds, and bleeding gums. It became known as El Tifu Negro (the Black Typhus, for the color of vomit and stool), and by late 1961 had struck 245 people, with a case fatality rate of 40 percent. It continued killing until the virus was isolated, its reservoir identified, and its dynamics of transmission understood well enough to be interrupted by preventive measures. Mouse trapping helped enormously. Most of the scientific work was done under difficult field conditions by a patched-together team of Americans and Bolivians, including an intense young scientist named Karl Johnson, pungently candid with his opinions, deeply enthralled by the dangerous beauty of viruses, who caught the disease himself and nearly died of it. This was before the Centers for Disease Control and Prevention (CDC) in Atlanta sent out well-equipped squads; Johnson and his colleagues invented their methods and tools as they went. Having struggled through his fever at a hospital in Panama, Karl Johnson would play a large and influential role in the longer saga of emerging pathogens.