Spillover: Animal Infections and the Next Human Pandemic

by David Quammen

Ebola and Marburg, would be classified within a new family, Filoviridae: the filoviruses.

The case fatality rate of 88 percent, they noted, was higher than any on record, apart from the rate for rabies (almost 100 percent among patients not treated before they show symptoms).

Monkeypox is a severe affliction, though not so dramatic as Ebola virus disease, and also caused by a virus that lurks in a reservoir host or hosts, at that time still unidentified.

It disappears entirely for years at a time. This is a mercy for public health but a constraint for science.

Viral ecologists can look for Ebola anywhere, in any creature of any species, in any African forest, but those are big haystacks and the viral needle is small.

The spleens were transferred to a biosafety level 4 (BSL-4) laboratory, a new sort of facility since Karl Johnson’s early work (and of which he was one of the pioneering designers), with multiple seals, negative air pressure, elaborate filters, and lab personnel working in space suits—a containment zone in which Ebola virus could be handled without risk (theoretically) of accidental release.

Once again, Ebola virus had spilled over, caused havoc, and then disappeared without showing itself anywhere but in the sick and dying human victims.

First, they suspected (based on earlier studies) that the reservoir is a mammal. Second, they noted that Ebola virus disease outbreaks in Africa had always been linked to forests. (Even the urban epidemic at Kikwit had begun with that charcoal-maker out amid the woods.)

Third, they noted also that Ebola outbreaks had been sporadic in time—with years sometimes passing between one episode and the next. Those gaps implied that infection of humans from the reservoir is a rare occurrence.

Rarity of spillover in turn suggested two possibilities: that either the reservoir itself is a rare animal or that it’s an animal...

The first question is ecological: In what living creature does it hide? That’s the matter of reservoir. The second question is geographical: What’s its distribution across the African landscape? The second may be impossible to answer until the reservoir is identified and its distribution traced.

You know about this if you’ve read The Hot Zone, Richard Preston’s account of a 1989 outbreak of an Ebola-like virus among captive Asian monkeys at a lab-animal quarantine facility in suburban Reston, just across the Potomac from Washington, DC.

after it tested positive for Reston virus, forty-nine others housed in the same room were euthanized as a precaution. (Most of those, tested posthumously, were negative.) Ten employees who had helped unload and handle the monkeys were also screened for infection, and they also tested negative, but none of them were euthanized.

The role of evolution in making Taï Forest virus (or any virus) less virulent in humans is a complicated matter, not easily deduced from simple comparison of case fatality rates. Sheer lethality may be irrelevant to the virus’s reproductive success and long-term survival, the measures by which evolution keeps score.

Like other zoonotic viruses, ebolaviruses have probably adapted to living tranquilly within their reservoir (or reservoirs), replicating steadily but not abundantly and causing little or no trouble. Spilling over into humans, they encounter a new environment, a new set of circumstances, often causing fatal devastation.

“dead-end host,” as distinct from “reservoir host,” to describe humanity’s role in the lives and adventures of ebolaviruses. What the term implies is this: Outbreaks have been contained and terminated; in each situation the virus has come to a dead end, leaving no offspring. Not the virus in toto throughout its range, of course, but that lineage of virus, the one that has spilled over, betting everything on this gambit—it’s gone, kaput. It’s an evolutionary loser. It hasn’t caught hold to become an endemic disease within human populations. It hasn’t caused a huge epidemic. Ebolaviruses, judged by experience so far, fit that pattern.

Advisory: If your husband catches an ebolavirus, give him food and water and love and maybe prayers but keep your distance, wait patiently, hope for the best—and, if he dies, don’t clean out his bowels by hand. Better to step back, blow a kiss, and burn the hut.

Viruses of each species have genomes that are at least 30–40% divergent from one another, a level of diversity that presumably reflects differences in the ecologic niche they occupy and in their evolutionary history.”

Towner and company suggested that some of the crucial differences between one ebolavirus and another—including the differences in lethality—might be related to where and how they live, where and how they have lived, within their reservoir hosts.

widespread, intuitive comprehension of zoonoses: Relations between humans and other animals, wild or domestic, must somehow lie at the root of the disease troubles. In

There were still five questions pending, he said, and he began to list them: (1) Why were only half of the members of each household affected? (2) Why were so few hospital workers affected, compared to other Ebola outbreaks? (3) Why did the disease strike so spottily within the Bundibugyo district, hitting some villages but not others? (4) Was the infection transmitted by sexual contact? After those four he paused, momentarily unable to recall his fifth pending question. “The reservoir?” I suggested. Yes, that’s it, he said: What’s the reservoir?

Molecular biology and epidemiology are useful, but other traditions of knowledge are useful too.

And, as the woman said, sorcery didn’t apply to gorillas.

“Bloody tears is bullshit. Nobody has ever had bloody tears.” Furthermore, Karl noted, “People who die are not formless bags of slime.” Johnson also concurred with Pierre Rollin that the bloodiness angle has been oversold. If you want a really bloody disease, he said, look at Crimean-Congo hemorrhagic fever. Ebola is bad and lethal, sure, but not bad and lethal precisely that way.

Ebola virus generally killed with a whimper, not with a bang or a splash.

If so, he was blurring the distinction between what Ebola virus does and what garden-variety bacteria can do in the absence of a healthy immune system keeping them cropped. But, hey, don’t we all like a dramatic story better than a complicated one?

Disseminated intravascular coagulation, he explained, is a form of pathological blood sludge, in which the normal clotting factors (coagulation proteins and platelets) are pulled out to form tiny clots along the insides of blood vessels throughout the victim’s body, leaving little or no coagulation capacity to prevent leakage elsewhere.

The tininess of Platt’s wound, in light of subsequent events, testifies that even a minuscule dose of an ebolavirus is enough to cause infection, at least if that dose gets directly into a person’s bloodstream.

It’s not very contagious but it’s highly infectious.

(BSL-3 comprises the laboratory suites in which researchers generally work on dangerous but curable diseases, many caused by bacteria, such as anthrax and plague. BSL-4 is reserved for work on pathogens such as Ebola, Marburg, Nipah, Machupo, and Hendra, for which there are neither vaccines nor treatments.)

One test, using the PCR (polymerase chain reaction) technique that’s familiar to all molecular biologists,

unfortunately

Ebola virus is not in your habitat. You are in its.

They found evidence suggesting that the medical outcome for an individual patient—to survive and recover, or to die—might be related not to the size of the infectious dose of Ebola virus but to whether the patient’s blood cells produced antibodies promptly in response to infection.

One method was designed to detect Ebola-specific antibodies, which would be present in animals that had responded to infection. The other method used PCR (as it had been used on Kelly Warfield) to screen for fragments of Ebola’s genetic material. Having looked so concertedly at the bat fauna, which accounted for two-thirds of his total collections, Leroy found something: evidence of Ebola virus infection in bats of three species.

Ebola virus in general seems to mutate at a rate comparable to other RNA viruses (which means relatively quickly), and the amount of variation detectable between one strain of Ebola virus and another can be a very important clue about their origins in space and time.

suggest that all known variants of Ebola virus descended from an ancestor closely resembling the Yambuku virus of 1976.

So much for the wave hypothesis. The particle hypothesis embraces much of the same data, construed differently, to arrive at a vision of independent spillovers, not a traveling wave.

Thus, Ebola outbreaks probably do not occur as a single outbreak spreading throughout the Congo basin as others have proposed,” Leroy’s team wrote, alluding pointedly to Walsh’s hypothesis, “but are due to multiple episodic infection of great apes from the reservoir.”

So . . . is light a wave or a particle? The coy, modern, quantum-mechanical answer is yes. And is Peter Walsh correct about Ebola virus or is Eric Leroy? The best answer again may be yes.

offering a logical amalgam of their respective views on the family tree of Ebola virus variants (all descended from Yambuku) and of the hammer-headed bat and those two other kinds of bats as (relatively new) reservoir hosts. But even that paper left certain questions unanswered, including this one: If the bats have just recently become infected with Ebola virus, why don’t they suffer symptoms?

First, fruit bats might be reservoirs of Ebola virus but not necessarily the only reservoirs.

Second, they agreed that too many people have died of Ebola virus disease, but not nearly so many people as gorillas.

For a long time Prosper stood holding the book, opened for us to see those names. He comprehended emotionally what the scientists who study zoonoses know from their careful observations, their models, their data. People and gorillas, horses and duikers and pigs, monkeys and chimps and bats and viruses: We’re all in this together.

2003, SARS

2003 SARS Epidemic

To say that “SARS got on a plane,” of course, is to commit metonymy and personification, both of which are forbidden to the authors of scientific journal articles but permissible to the likes of me.

Two aspects of what made SARS so threatening were its degree of infectiousness—especially within contexts of medical care—and its lethality, which was much higher than in familiar forms of pneumonia.

Lack of basic communication, let alone resistance to collaborative work and sharing of clinical samples, caused problems and delays in responding to SARS. The problems were eventually solved but the delays were consequential.

One of those teams prepared an advisory document on the new ailment, labeling it “atypical pneumonia” (feidian in Cantonese). That was the phrase, a common though vague formulation, used weeks later by WHO in its global alert. An atypical pneumonia can be any sort of lung infection not attributable to one of the familiar agents, such as the bacterium Streptococcus pneumoniae. Applying that familiar label tended to minimize, not accentuate, the uniqueness and potential severity of what was occurring in Zhongshan. This “pneumonia” was not just atypical; it was anomalous, fierce, and scary.

A superspreader is a patient who, for one reason or another, directly infects far more people than does the typical infected patient.

R0 (that important variable introduced to disease mathematics by George MacDonald) represents the average number of secondary infections caused by each primary infection at the start of an outbreak, a superspreader is someone who dramatically exceeds the average.