Spillover

by David Quammen

  High-density dairy-goat husbandry, Dutch style—that’s one factor among several to account for the recent outbreaks, Roest said. Factor two was concomitant to factor one: proximity of humans. The Netherlands is a crowded country, containing 16 million people within an area half the size of Indiana, and many of those high-density goat farms are sited near towns and cities. Factor three was the weather: Yes, very dry springtime conditions, during each year since 2007, had doubtless exacerbated the airborne spread of the bacterium. And Roest suspected a fourth factor: It might be, he said, that the nature of the bug itself had changed. An evolutionary twitch could have enabled an ecological leap.

  His molecular data showed that one particular genetic strain of the bacterium—one among fifteen that his team identified—had come to predominate. “On all farms in the high-risk area,” by which he meant Noord-Brabant and some adjacent zones, “and on the two dairy farms outside,” which also tested positive, “there is one genotype present in 90 percent of all samples. And that is what we call the CbNL-01.” CbNL-01 seems a fancy cryptogram but it connotes simply “Coxiella burnetii, Netherlands, genotype #1.” Such disproportionate representation suggested that a mutation in that strain might have made it especially aggressive, efficient, transmissible, and fierce.

  Dutch officials tried to cope with this crisis by means of some forceful, if inconsistent, regulatory measures. In June 2008, shortly after the outbreak among patients at the psychiatric facility in Nijmegen, Q fever became a “notifiable” disease for dairy goats and dairy sheep, meaning that veterinarians were required to notify the government about any abortion storms. (It had been a notifiable disease with regard to human cases since 1975.) Another regulation, issued the same day, prohibited farmers from removing manure from an infected stable or deep litter shed for three months following notification of an outbreak. Almost a year later, in April 2009, as the pattern of outbreaks continued on dairy-goat farms and the number of human cases ascended faster than ever, a program of mandatory vaccination against Q fever went into effect. This order applied to all dairy goats and sheep on farms with more than fifty animals, and to zoos and “care farms” such as the one at Nijmegen, where the general public might come into close contact with infected animals. By November 2009, more than a quarter million goats and sheep had been vaccinated, at government expense—but the human case count for the year was alarmingly high, and concern had spread widely through the Dutch media. So in early December 2009, a ban was decreed on the breeding of goats: no more pregnant nannies allowed until further notice. Closer consideration revealed that was too little, too late. Many females had already been bred. One week later, on advice from an expert panel, the government announced that all currently pregnant goats and sheep (including those recently vaccinated) on affected dairy farms would be culled.

  Veterinary teams went out to do the deeds. One dairyman, awaiting the cullers, told a reporter that his animals would be less agitated if he remained with them, but “I just don’t know if I can watch it.” The eventual toll included about fifty thousand dead goats and scores of angry, frustrated farmers, who were compensated for the value of each animal but not for lost revenue as they faced rebuilding their herds, nor for emotional stress. “It was also distressing for the veterinarians,” Hendrik-Jan Roest told me—and distressing too, as he could say from experience, “for the veterinary advisors.”

  Despite all these measures, and the disappearance of pregnant goats from the Dutch landscape, Q fever did not disappear—not entirely, not at once. The bacterium was still out there in some abundance. In its small, sturdy form, it could survive in the fetid wastes on infected farms for as long as five months. In its large form, it could replicate in a variety of animals. Highly robust but not too specialized, it was capable of invading a wide range of hosts, and had been found not just in goats and sheep but also in cattle, rodents, birds, amoebae, and ticks. An enterprising organism and, as Macfarlane Burnet had noted, quite versatile.

  In time the regulatory measures had some effect, and another spring passed, this one without many newborn or aborted kids. The rate of new human cases declined from its 2009 peak. By the middle of July 2010, only 420 more Netherlanders had been diagnosed with Q fever. The ministry officials could feel guardedly optimistic that their public health crisis had been brought under control. The doctors could relax slightly. The dairy farmers could lament their losses. But the scientists knew that Coxiella burnetii wasn’t gone. It had waited for ideal conditions before, and it could wait again.

  47

  Back in Australia, around the time of his work on Q fever and psittacosis, smart and curmudgeonly Macfarlane Burnet began thinking more broadly about infectious diseases, not so much from the medical perspective as from the viewpoint of a biologist. During the late 1930s he drafted a book on the subject, in the opening pages of which he paid tribute to the great nineteenth-century founders of bacteriology, especially Pasteur and Koch, who had finally provided a rational basis for concerns over clean drinking water, decent sewage disposal, food untainted with rot, and antiseptic surgical techniques. It was a qualified tribute, concluding on page two, after which Burnet got to his real point.

  Those men and their colleagues, he wrote, “were on the whole too busy to think of anything but the diseases for which bacteria were responsible, and how these might be prevented.” They gave little consideration to the microbes as beings in their own right, or to “how their nature and activities fitted into the scheme of living things.” Most bacteriologists were trained as medical men—Burnet himself had been, before going into bacteriological research—and “their interest in general biological problems was very limited.” They cared about curing and preventing diseases, which was well and good; less so about pondering infection as a biological phenomenon, a relationship between creatures, equal in fundamental importance to such other relationships as predation, competition, and decomposition. Burnet’s purpose in the book was to rectify that slight. He published Biological Aspects of Infectious Disease in 1940, a landmark along the route to modern understandings of zoonoses on a crowded, changing planet.

  Burnet didn’t claim that the broader perspective was uniquely his own. He recognized it as a salubrious trend. Biochemists had begun applying their methods to disease-related questions, with considerable success, and there was also new interest at the level of organisms (even single-celled organisms) as highly adapted creatures with their own life histories in the wild. He wrote:

  Other workers with an appreciation of modern developments in biology are finding that infectious disease can be thought of with profit along ecological lines as a struggle for existence between man and micro-organisms of the same general quality as many other types of competition between species in nature.

  The italics are mine. Thinking “along ecological lines,” and about the “struggle for existence” (a phrase that came straight from Darwin), was what Burnet specially offered: a book on the ecology and evolution of pathogens.

  He preferred the term “parasites,” used in its looser sense. “The parasitic mode of life is essentially similar to that of the predatory carnivores. It is just another method of obtaining food from the tissues of living animals,” though with parasites the consumption tends to be slower and more internalized within the prey. Small creatures eat bigger ones, generally from the inside out. This is just what I was getting at, back at the start, when I mentioned lions and wildebeests, owls and mice. The main problem facing a parasite over the long term, Burnet noted, is the issue of transmission: how to spread its offspring from one individual host to another. Various methods and traits have developed toward that simple end, ranging from massive replication, airborne dispersal, environmentally resistant life-history stages (like the small form of C. burnetii), direct transfer in blood and other bodily fluids, behavioral influence on the host (as exerted by the rabies virus, for instance, causing infected animals to bite), passage through intermediate or amplifier hosts, and the use of insect and
arachnid vectors as means of transportation and injection. “It will be clear, however,” Burnet wrote, “that no matter by what method a parasite passes from host to host, an increased density of the susceptible population will facilitate its spread from infected to uninfected individuals.” Increased density: Crowded hosts allow pathogens to thrive. Macfarlane Burnet may or may not have been influenced by those early mathematical works on infectious disease—the differential equations of Ronald Ross, the 1927 paper by Kermack and McKendrick—but he was putting some of the same points into plain English prose in a book that was both authoritative and accessible.

  Biological Aspects of Infectious Disease was later revised and reissued, in 1972, as Natural History of Infectious Disease. Though even its revised version seems antiquated today (new diseases have emerged, as well as new insights and new methods), the book was a valuable contribution in its time. It offered no erudite mathematical models but it spoke plainly on the subject of what disease scientists do, and what they should do. What they should do, by his lights, was to think about infectious pathogens in ecological and evolutionary terms as well as medical ones.

  Parrot fever was one of his exemplary cases. It had the attractions of an Australian connection (for him, a local bug) plus global reach, and it illustrated a favorite point. “Like many other infectious diseases, psittacosis was first recognized as a serious epidemic disease of human beings, but as its nature became gradually understood, it grew clear that the epidemic phase was only an accidental and relatively unusual happening.” The bacterium had its own life to lead, that is, of which infecting humans was just one part—and arguably a digression.

  Burnet retold the tale of the California-bred parakeets, the wild Australian cockatoos, the infection of working-class Melbourne bird fanciers by animals sold out of Mr. X’s dismal backyard shed. Psittacosis, Burnet noted, is not normally very infectious. It exists endemically among wild bird populations, causing little trouble. One could reasonably suppose that “those cockatoos, left to a natural life in the wild, would never have shown any symptoms.” But the bird catcher, and then Mr. X as middleman, had disrupted their natural life. “In captivity, crowded, filthy and without exercise or sunlight, a flare-up of any latent infection was only to be expected.” The stressful conditions had allowed Chlamydophila psittaci (as Rickettsia psittaci later became known, after another of those taxonomic revisions) to replicate and erupt.

  This case and similar ones, Burnet wrote, embodied a general truth about infectious disease. “It is a conflict between man and his parasites which, in a constant environment, would tend to result in a virtual equilibrium, a climax state, in which both species would survive indefinitely. Man, however, lives in an environment constantly being changed by his own activities, and few of his diseases have attained such an equilibrium.” Burnet was right on the big ideas, including that one: environmental disruption by humans as a releaser of epidemics. Still, he couldn’t foresee the particulars of what would come. Publishing in 1940, he focused on several infectious diseases in addition to psittacosis: diphtheria, influenza, tuberculosis, plague, cholera, malaria, yellow fever. These were the old, familiar, infamous scourges, fairly easy to recognize though not well enough understood. Our modern age of emerging viruses was just beyond the reach of his headlights.

  48

  Burnet didn’t mention Lyme disease but, because it shares one important characteristic with Q fever and psittacosis, I will. The most fundamental thing about this newly emergent or re-emergent infection is that it’s not caused by a virus. The Lyme agent, like Coxiella burnetii and Chlamydophila psittaci, is an anomalous, crafty bacterium.

  Lyme disease is hotly controversial, though, in a way that Q fever and psittacosis are not. Segments of the scientific and medical communities, plus victims or supposed victims, can’t even agree (especially they can’t agree) on who has the disease and who doesn’t. Roughly thirty thousand cases of Lyme disease were reported in the United States during a recent year, and more than twenty thousand per year as a ten-year average. You probably know someone who has had it; you may well have had it yourself. By any standard, it’s the most commonly reported vector-borne disease in the United States. But do those thirty thousand cases in one year represent the true total of affected Americans or only a small fraction of the real number of cases, most of which go undiagnosed? Is there such a thing as “chronic Lyme disease,” which eludes detection by conventional diagnostics, persists despite prescribed treatment with antibiotics, and causes gruesome suffering among people who can’t persuade their doctors or their insurance companies that they are genuinely infected? Does Borrelia burgdorferi hide in the body and somehow later recrudesce?

  Disagreements on such points have stretched all the way from the examining room to the courtroom, making Lyme not just the most common infection of its kind but also the most confusingly politicized. For instance, in 2006 the Infectious Diseases Society of America suggested in its guidelines for treatment that “chronic Lyme disease” is an illusion. More precisely, the IDSA wrote: “No convincing biologic evidence exists for symptomatic chronic B. burgdorferi infection in patients after recommended treatment regimens for Lyme disease.” The recommended treatment regimens, involving two to four weeks on an antibiotic (such as doxycycline or amoxicillin), should cure the disease itself. What the IDSA carefully labeled “post-Lyme disease syndrome” was another matter. Implication: These people are head cases. That dismissiveness about the possibility of lingering Lyme infection infuriated many mysteriously tortured patients, who believed that they had it and who (counseled by certain private physicians, contra the IDSA) felt they should be treated with high doses of antibiotics given intravenously over a much longer term—months or years. Such treatments, by the conventional view, might actually be harmful to a patient’s health. They are also a matter of consequence to insurance companies that don’t want to pay for them.

  In late 2006, the attorney general of Connecticut (Richard Blumenthal, later a US senator) began an antitrust investigation into the IDSA and the way it formulated its Lyme treatment guidelines. Had there been conflicts of interest? Blumenthal thought so. The IDSA’s Lyme disease guideline panel undercut its own credibility, he said, “by allowing individuals with financial interests—in drug companies, Lyme disease diagnostic tests, patents and consulting arrangements with insurance companies—to exclude divergent medical evidence and opinion.” He emphasized, though, that his scrutiny was directed at the guideline formulation process, not at the science itself. Two years later the IDSA and Blumenthal agreed on a compromise settlement, whereby the guidelines would be reviewed by a new, independent panel. In 2010, the independent panel unanimously reaffirmed the original guidelines. They too saw “no convincing evidence for the existence of chronic Lyme infection.” Furthermore, they warned, long-term intravenous treatment with antibiotics was worse than useless; it could lead to deadly blood infections, severe drug reactions, disruption of normal gut flora (the beneficent bacteria that help people digest), consequent diarrhea as other bacteria took hold, and the creation of antibiotic-resistant “superbugs,” menacing not just to patients under such treatment but to all the rest of us also.

  Another complication of the whole story is that, though Lyme disease seems like a new problem, unnoticed before 1975, it has probably been around for a long time, not just in the United States but also in Europe and Asia. For decades it was detected marginally and piecemeal, by some of its symptoms, but not recognized as a single syndrome with a single cause. Only in retrospect were the pieces assembled into a pattern with a name.

  This prehistory period began in 1909, when a Swedish dermatologist named Arvid Afzelius reported the case of a woman, bitten by a sheep tick, who suffered a rosy rash that spread like concentric ripples. Afzelius called the condition erythema migrans (“spreading redness”) and wrote about it for a German journal devoted largely to syphilis, which was a major concern of dermatologists back then. (There was some similarity: Syp
hilis is caused by a bacterium of the type known as spirochetes, the same group of corkscrewing creatures that includes Borrelia burgdorferi, the Lyme disease pathogen.) Afzelius didn’t claim to know the cause of the woman’s rash, but over the next dozen years he saw a similar pattern in five more patients. Other physicians in Europe also began noticing such annular rashes, each resembling a target with a tiny red dot as the bull’s-eye. In some cases, the rash was associated with the bite of an unidentified arthropod (an insect, a spider, a tick?), and often it came with more serious symptoms. Sven Hellerstrom, another Swedish dermatologist, reported in 1930 seeing a man with the distinctive red rash, plus meningitis. As years passed, Hellerstrom found that annular rashes, resulting from tick bites and sometimes involving meningitis, were far from rare in the Stockholm area.

  Almost two decades after his first report, Dr. Hellerstrom crossed the Atlantic to attend a medical conference in Cincinnati, where he described his continuing work. The cause of the rash-and-meningitis syndrome, he postulated, was a spirochete. Because the conference was sponsored by the Southern Medical Association, a printed version of Hellerstrom’s 1949 talk appeared in the Southern Journal of Medicine, an otherwise unlikely outlet for a Swedish clinician. These were not high-profile publications, neither the papers of Afzelius nor of Hellerstrom nor the others, and of course there was no Internet, no Google, no PubMed, nor any other such means by which to summon obscure citations at the touch of a few keys. But a good memory, broad education, and luck could serve the same purpose.