Spillover: Animal Infections and the Next Human Pandemic (27 page)

Those birds, all forty-nine of them, had been sold by the bird catcher to a Melbourne man, a laborer, who dabbled in bird dealing for a bit of seasonal income. Burnet called the man Mr. X, giving him the usual medical anonymity. Mr. X kept his avian merchandise in a small, dark, backyard shed. The first signal of disease in the birds, several weeks after their transfer to his “aviary,” was that eight or nine of them died. But by then Mr. X, wasting no time, had sold seven others to people in the neighborhood and sent his twelve-year-old son off to the local market with twenty more. Mr. X’s son got sick, and his daughter, and his wife, and his mother-in-law. Five neighbors and three other people, each of whom lived in a house with a cockatoo bought from Mr. X or his son, also fell ill, some of them severely. Nobody died. Mr. X himself didn’t sicken, not on this occasion—possibly because there is no justice in the world, though more likely because exposure to
Rickettsia psittaci
during his earlier bird dealings had given him some acquired immunity.

Macfarlane Burnet, as a biologist as well as a physician, was interested in the birds and the bacterium, not just in the people. He knew that the sulphur-crested cockatoo nests in tree holes, producing two or three eggs in a clutch, and that bird catchers typically raided the nest holes just before fledging. He suspected that almost all the young became infected with the bacterium as hatchlings, before leaving (or being taken from) the nest. “
If the young cockatoo, after capture
, is kept under good conditions,” he and his coauthor wrote, “it remains healthy and presents no danger to human beings.” Likewise, the wild bird populations might carry a high prevalence of infection but suffer little impact in terms of damaged health or mortality. “When, on the other hand, birds are crowded into small spaces, with inadequate food and sunlight, their latent infection is lit up.” The bacterium multiplies and “is excreted in large amounts.” It floats out of the cages along with downy feathers, powdered dung, and dust. It rides the air like a Mosaic plague. People inhale it and become ill. Burnet acknowledged that no government in Australia was likely to prohibit the sale of cockatoos, not in those days, nor even to insist they be kept under decent conditions. But that’s what is needed, he added gruffly. Then he turned to another disease.

44

T
he other disease was Q fever. Remember those abattoir workers in Brisbane, during the early 1930s, who suffered mysterious, feverish ailments resembling typhus? The job of investigating that cluster of cases fell first to a man named Edward H. Derrick, newly appointed as director of the microbiology laboratory at the Queensland Health Department. Using guinea pigs inoculated with patients’ blood to start a sequence of infections and then infecting one guinea pig from another, Derrick established the presence of “
a distinct clinical entity
,” a new sort of pathogen, not recognizable by any of the standard lab tests for typhus, undulant fever, or other familiar possibilities. But he couldn’t see the new thing through a microscope, nor could he get it to grow in a dish. That led him to suspect it was a virus. So he sought help from Macfarlane Burnet.

In October 1936, Derrick sent Burnet a sample of guinea-pig liver, infected experimentally with whatever had been raging through the abattoir workers. From that sample, Burnet and a laboratory assistant continued the chain of infection in more guinea pigs, and also in a series of inoculated mice. Like Derrick, Burnet and his assistant checked for bacterial pathogens and found none. So they suspected “
a filterable virus,
” meaning an agent so small it would pass through a fine filter designed to screen out bacteria. They took a thin smear of puréed spleen from an infected mouse, stained it for microscopy, and looked through the scope. Thirty years later, Burnet recalled: “
Most significant discoveries just grow on one
over weeks or months. Recognition of Q fever as a rickettsiosis was, however, an exception datable to the minute.” What he saw were tiny rod-shaped “inclusions” within some of the spleen cells. For a better view, he tried another slide of spleen using a different stain. This one showed an abundance of the rods, some within spleen cells and some floating free. “
From that moment, there was no doubt
in my mind about the nature of the agent responsible for Q fever.” It was another new rickettsia, he concluded, not too unlike the one that caused parrot fever.

In his later recollection, characteristically blunt, Burnet told how the disease got its name:

Problems of nomenclature arose
. The local authorities objected to “abattoir’s fever”, which was the usual name amongst the doctors in the early period. In one of my annual reports I referred to “Queensland rickettsial fever”, which seemed appropriate to me, but not to people concerned with the good name of Queensland. Derrick, more or less in desperation, since “X disease” was preoccupied by [
sic
, meaning “already applied to”] what is now Murray Valley encephalitis, then came out for “Q” fever (Q for “query”). For a long time, however, the world equated Q with Queensland, and it was only when the disease was found to be widespread around the world that “Q fever” came to stand firmly in its own right as the name of the disease.

For the scientific binomial, Derrick proposed
Rickettsia burnetii
, to honor Burnet’s role in finding and identifying the bug. The genus name,
Rickettsia
, would eventually change due to a taxonomic revision, but Burnet’s half stuck.

Meanwhile, nine thousand miles away, the same pathogen came under scrutiny by a much different route, when two bacteriologists at the Rocky Mountain Laboratory, in Hamilton, Montana, found it in ticks from a place called Nine Mile, a Civilian Conservation Corps camp in the mountains northwest of Missoula. These two weren’t looking for abattoir fever. Gordon Davis, the first on the hunt, had brought the ticks into his lab for research on the ecology of two other diseases, Rocky Mountain spotted fever and tularemia. Setting the ticks onto guinea pigs, he watched one guinea pig become sick with something he couldn’t identify. For a while it was simply “
the Nine Mile agent
.” Herald Cox, joining the laboratory a year later, helped Davis isolate it and recognize that it was probably a rickettsia. Then another man entered the fray, an infectious disease expert who was also a powerful administrator at the National Institutes of Health, with supervisory responsibility for Cox, Davis, and their colleagues at the Rocky Mountain Laboratory. His name was Dr. Rolla Dyer. Dr. Dyer seems to have been a bit of a bullhead, but not irredeemably so. Strongly skeptical of Cox’s claim to have found that the Nine Mile agent was a rickettsia, he stormed out to Montana and into Cox’s lab. Cox showed him evidence on a microscope slide. Dyer reversed himself, acknowledged the discovery, and stayed around in Hamilton just long enough, assisting Cox with the work, to catch a dose of Q fever himself. Ten days after returning to Washington, he felt “
sharp pains in the eyeballs
,” followed by chills, followed by fever and night sweats for a week. Maybe there’s some justice to zoonotic diseases after all. But probably not, just a high degree of infectiousness in Q fever, because by that time Macfarlane Burnet had caught it too. Both he and Rolla Dyer recovered.

As for Herald Cox, he was further vindicated when, in 1948, the pathogen was recognized as different enough from all other
Rickettsia
to deserve its own genus and was renamed
Coxiella burnetii,
honoring him as well as Macfarlane Burnet. That name remains today
.

“
There is no disease to match Q fever
for queer stories,” wrote Burnet, in the little memoir he published in 1967. First, he claimed, it was “a record-breaker” for producing laboratory infections, such as his own, Dyer’s, and similar illnesses in two secretaries at the Hall Institute. (He may have wrongly ignored the laboratory-infection claims of psittacosis.) Second, he noted the high incidence of what had been called “Balkan grippe” during the Great War, especially among German troops in Greece and New Zealanders in Italy. Furthermore, a shipload of American soldiers had been assembled “for a night or two near Bari in southern Italy, prior to embarkation,” more than half of whom took sick by the time their boat reached home. “Sooner or later, all these episodes were established as Q fever.” After the war, research showed “the extraordinary versatility of
C. burnetii
as a parasite,” infecting dairy cows in California, sheep in Greece, rodents in North Africa, and bandicoots back home in Queensland. It passed from one species to another in the form of minuscule airborne particles, often dispersed from the placenta or the dried milk of an infected female animal, inhaled, and then activated through the lungs, or taken directly into the bloodstream from the bite of a tick. As he said, it was versatile.

“
One of the more bizarre episodes
concerns an English class of art students,” Burnet recounted with some enthusiasm. “Around 1950, a collection of casts from classic statuary was ordered from Italy. The crates arrived with the casts packed in straw, and everyone in the class lent a hand in unpacking. Most of them got Q fever, but no one knows how the straw was contaminated.” All of this, Burnet wrote, “was the beginning of an ever-widening recognition of Q fever across the world.” He was right. Though
Coxiella burnetii
is now known as a bacterium, not an anomalous form halfway between bacteria and viruses, its impact on human health didn’t disappear with the development and mass production of antibiotics during the 1940s. As recently as 2007, Q fever caused serious trouble in a modern European country, far removed from both Queensland and Montana: the Netherlands.

45

F
ifty miles southeast of Utrecht, amid the flat landscape and tangled roadways of the Dutch province of Noord-Brabant, lies a little back-road village called Herpen. It’s a tidy place, largely assembled from red brick: redbrick farmhouses on the outskirts, redbrick cottages in town, cobbled sidewalks, and a handsome old redbrick church. The farmhouses, some shielded behind pruned hedges and prim gardens, command fields of hay and corn, grown for fodder to feed livestock that shelter in large, low, redbrick barns. Although it looks like a farm village, Herpen nowadays is a bedroom community for laborers and contractors in the building business. A few workhorses stand idle in pastures, kept company by a modest number of cows, sheep, and pigs. But the agricultural component of the local economy, insofar as it still exists, is committed more heavily to dairy goats. They seem to have been the source of the problem in 2007.

Nannies had given birth to their kids during the usual kidding season, which can stretch from January to as late as April. Mostly those births had gone well, though on certain farms of the province, including at least one in the Herpen area, many females aborted during the last month of pregnancy. Even full-term kids seemed a bit weak and puny, with a higher mortality rate than usual. Evidently something was troubling the goats, an infection of some sort, possibly new, and veterinarians took note, trying to forestall the abortions with antibiotics. That didn’t help. The general public noticed this situation little or not at all.

Then came a balmy spring—far warmer and drier than normal. In April, by the recollection of one resident, “
there was no drop of rain
.” Even before summer arrived, lands surrounding the village had gotten dusty. Breezes blew. In early May, people began to get sick.

A local physician named Rob Besselink, with an office in Herpen, saw an odd, flulike ailment in several of his patients: high fever, severe headache, muscle aches, shortness of breath, coughing. Was it a bacterial pneumonia? “We started treating them,” Besselink said later, “and it turned out that they didn’t react as we expected them to react on the antibiotics they were given.” He discussed it with a colleague. “After that first week we said to each other, ‘There’s something strange going on,’ because I had three or four people having the same symptoms, and he had also two or three.” Within a couple weeks, the two doctors had seen about twenty patients fitting the profile, of whom almost a dozen, unresponsive to antibiotics, had to be hospitalized.

Around the same time, in another part of Noord-Brabant, a medical microbiologist named Ineke Weers, employed at a regional laboratory, heard murmurings about a similar cluster. Despite Weers’s broad training and experience—she was an MD with a PhD in microbiology and twenty-one years of work in the diagnostics of infectious diseases—this turned out to be something new to her. An internist at one of the hospitals mentioned that doctors there had lately seen quite a few patients with an atypical, antibiotic-resistant pneumonia. Did Weers know what it might be? Had she read anything about such a syndrome? No, nothing, she answered. But she offered to call the Municipal Health Service in Den Bosch, a large city nearby, and ask whether those authorities could offer some glimmer of insight or advice. They could not; they had heard no other such reports.

Four days later, Rob Besselink called the same office of the MHS about his situation in Herpen. Two weeks after that, another general practitioner in Noord-Brabant made a similar report to the MHS. This aggregation of puzzling cases was enough to trigger the beginnings of a response. The physicians took blood samples, some of which went to a nearby laboratory, some to a more specialized lab, where the sera were tested for antibodies. After a bit of confusion about what sort of microbe might be causing such “atypical pneumonia,” both labs eventually converged on an answer: It was
Coxiella burnetii
, the agent of Q fever.

Q fever wasn’t unknown in the Netherlands but for fifty years it had been blessedly rare. Although the bacterium seemed to be endemic among livestock populations, based on occasional surveys, it had seldom caused noticeable disease in cows, in sheep, or in humans. Now the outbreak in Noord-Brabant caught the attention of the National Institute for Public Health and the Environment (commonly known by its Dutch initials, RIVM), up near Utrecht. Scientists there made an informed guess that maybe the high incidence of abortions on dairy goat farms, which had begun back in 2005, and which had been diagnostically linked to Q fever, might be a source of the human cases.
Coxiella burnetii
was known to be capable of airborne transmission. At this point, RIVM sent people south to the village of Herpen and surrounding areas to conduct a study. Someone had to learn what was happening downwind of the goats.