Spillover: Animal Infections and the Next Human Pandemic

by David Quammen

For exactly that reason, it marks a good point from which to begin toward understanding the emergence of certain virulent new realities on this planet—realities that include the death of more than 30 million people since 1981. Those realities involve a phenomenon called zoonosis.

A zoonosis is an animal infection transmissible to humans. There are more such diseases than you might expect. AIDS is one.

Rail went into the hospital, worsened there, and, after a week of intensive care, died.

All of the human influenzas are zoonoses. So are monkeypox, bovine tuberculosis, Lyme disease, West Nile fever, Marburg virus disease, rabies, hantavirus pulmonary syndrome, anthrax, Lassa fever, Rift Valley fever, ocular larva migrans, scrub typhus, Bolivian hemorrhagic fever, Kyasanur forest disease, and a strange new affliction called Nipah

encephalitis, which has killed pigs and pig farmers in Malaysia. Each of them reflects the action of a pathogen that can cross into people from other animals. AIDS is a disease of zoonotic origin caused by a virus that, having reached humans through just a few accidental events in western and central Africa, now passes human-to-human by the millions.

Zoonotic pathogens can hide. That’s what makes them so interesting, so complicated, and so problematic. Monkeypox is a disease similar to smallpox, caused by a virus closely related to variola.

Nearly all zoonotic diseases result from infection by one of six kinds of pathogen: viruses, bacteria, fungi, protists (a group of small, complex creatures such as amoebae, formerly but misleadingly known as protozoans), prions, and worms.

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.

Human-caused ecological pressures and disruptions are bringing animal pathogens ever more into contact with human populations, while human technology and behavior are spreading those pathogens ever more widely and quickly. There are three elements to the situation. One: Mankind’s activities are causing the disintegration (a word chosen carefully) of natural ecosystems at a cataclysmic rate.

Two: Those millions of unknown creatures include viruses, bacteria, fungi, protists, and other organisms, many of which are parasitic. Students of virology now speak of the “virosphere,” a vast realm of organisms that probably dwarfs every other group.

Three: But now the disruption of natural ecosystems seems more and more to be unloosing such microbes into a wider world. When the trees fall and the native animals are slaughtered, the native germs fly like dust from a demolished warehouse.

Will the Next Big One come out of a rainforest or a market in southern China? Will the Next Big One kill 30 or 40 million people?

There’s even a journal dedicated to the subject, Emerging Infectious Diseases, published monthly by the CDC.

Emergence and spillover are distinct concepts but interconnected. “Spillover” is the term used by disease ecologists (it has a different use for economists) to denote the moment when a pathogen passes from members of one species, as host, into members of another.

Eventually thirty-one people got sick, of whom twenty-one died: a case fatality rate of almost 68 percent.

Leroy and his colleagues found evidence of Ebola virus in samples from some patients, and they deduced that the butchered chimpanzee had been infected with Ebola. “The chimpanzee seems to have been the index case for infecting 18 primary human cases,” they wrote. Their investigation also turned up the fact that the chimp hadn’t been killed by village hunters; it had been found dead in the forest and scavenged.

Never eat underooked chimpanzee.

The spillover at Mayibout 2 was no isolated event. It was part of a pattern of disease outbreaks across Central Africa—a pattern of which the meaning is still a matter of puzzlement and debate. The disease in question, once known as Ebola hemorrhagic fever, is now simply called Ebola virus disease. The pattern stretches from 1976 (the first recorded emergence of Ebola virus) to the present, and from one side of the continent (Côte d’Ivoire) to the other (Sudan and Uganda). The four major lineages of virus that

Any such spillover in the reverse direction—from humans to a nonhuman species—is known as an anthroponosis.

But the question of its reservoir was less urgent than other concerns, such as how to break the chain of person-to-person transmission, how to keep patients alive, how to end the outbreak. “Only limited ecological investigations were made,” the team reported later, and the results of those investigations were all negative. No sign of Ebola virus appeared anywhere except in humans.

The later published report, with Johnson again as coauthor, only noted suggestively, in describing the girl’s native area: “Contact with nature is intimate, with villages located in clearings of the dense rain forest or along the rivers of the savannah.” Had she touched a dead chimpanzee, breathed rodent urine in a dusty shed, or pressed her lips to the wrong forest flower?

The Towner paper contained a very interesting statement, as an aside, concerning the five ebolaviruses: “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.”

Asked to elaborate, one villager explained that ezanga are “bad human-like spirits that cause illness in people” as retribution for accumulating material goods and not sharing.

These behaviors included quarantining each patient in a house apart from other houses; relying on a survivor of the epidemic (if there were any) to provide care to each patient; limiting movement of people between the affected village and others; abstaining from sexual relations; not eating rotten or smoked meat; and suspending the ordinary burial practices, which would involve an open casket and a final “love touch” of the deceased by each mourner, filing up for that purpose.

“This illness is killing everyone,” one local man told the Hewletts, and therefore it couldn’t be sorcery, which targets individual victims or their families.

Another of their informants, an Mbomo woman, declared: “Sorcery does not kill without reason, does not kill everybody, and does not kill gorillas or other animals.” Oh, yes, again gorillas. That was another aspect of the Mbomo brew—everyone knew there were dead apes in the forest all roundabout.

You may recall his depiction of a Sudanese hospital in which the virus “jumped from bed to bed, killing patients left and right,” creating dementia and chaos, and not only killing patients but causing them to bleed profusely as they died, liquefying their organs, until “people were dissolving in their beds.” You may have shuddered at Preston’s statement that Ebola virus in particular “transforms virtually every part of the body into a digested slime of virus particles.” You may have paused before turning the page when he told you that, after death, an Ebola-infected cadaver “suddenly deteriorates,” its internal

a French expatriate, living in Africa, who “essentially melts down with Marburg virus while traveling on an airplane.”

Preston described victims in a darkened Sudanese hut: comatose, motionless, and “bleeding out.”

more. “Droplets of blood stand out on the eyelids: You may weep blood. The blood runs from your eyes down your cheeks and refuses to coagulate.” The mask of red death—where medical reporting meets Edgar Allan Poe.

Testing the efficacy of this treatment required exposing additional horses. “It is difficult to describe working with a horse infected with Ebola,” according to the dry, cautious statement from Russia’s chief biowarfare man at the time, a lieutenant general named Valentin Yevstigneyev, in the Ministry of Defense.

“Taken together, our results clearly point to the conclusion that [Ebola virus] has gradually spread across central Africa from an origin near Yambuku in the mid-1970s,” they wrote.

So SARS had gone halfway around the world and back, in two airline leaps, over the course of six weeks. If circumstances had been different—less delay on the ground in Toronto, an earlier visitor headed from there to Luzon or Singapore or Sydney—the disease could have completed its global circuit far more quickly.

Around the same time, officials at WHO headquarters in Geneva issued a global alert about these cases of unusual pulmonary illness in Vietnam and China. (Canada and the Philippines weren’t mentioned because this was just before their involvement was recognized.) In Vietnam, said the statement, an outbreak had begun with a single patient (the one Carlo Urbani examined) who was “hospitalized for treatment of severe, acute respiratory syndrome of unknown origin.” The little comma after “severe” reflects the fact that those three adjectives and one noun hadn’t yet been codified into a name. Several days later, as the pattern of hopscotching outbreaks continued to unfold, WHO issued another public statement of alarm. This one, framed as an emergency travel advisory, marked the transformation of a descriptive phrase into a label. “During the past week,” it said, “WHO has received reports of more than 150 new suspected cases of severe acute respiratory syndrome (SARS), an atypical pneumonia for which cause has not yet been determined.”

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. The advisory document, which went

“Population estimates of R0 can obscure considerable individual variation in infectiousness,” according to J. O. Lloyd-Smith and several colleagues, writing in the journal Nature, “as highlighted during the global emergence of severe acute respiratory syndrome (SARS) by numerous ‘superspreading events’ in which certain individuals infected unusually large numbers of secondary cases.” Typhoid Mary was a legendary superspreader.

“Each time they began to insert the tube,” according to an account by Thomas Abraham, a veteran foreign correspondent based in Hong Kong, there was “an eruption” of bloody mucus. Abraham continues: It splashed on to the floor, the equipment and the faces and gowns of the medical staff. They knew the mucous [sic] was highly infectious, and in the normal course of things, they would have cleaned themselves up as quickly as possible. But with a critically ill patient kicking and heaving around, a tube half-inserted into his windpipe and mucous and blood spurting out, there was no way any of them could leave.

“The animals are packed in tiny spaces and often in close contact with other wild and/or domesticated animals such as dogs and cats,” the survey team wrote. “Many are either sick or with open wounds and without basic care. Animals are often slaughtered inside the markets in several stalls specialising in this.” Open wire cages, stacked vertically, allowed wastes from one animal to rain down onto another. It was zoological bedlam. “The markets also provide a conducive environment,” the team noted, almost passingly, “for animal diseases to jump hosts and spread to humans.”

The civets might have become infected “from another, as yet unknown, animal source, which is in fact the true reservoir in nature.”

An infectious consignment of bats serendipitously juxtaposed with a susceptible amplifying species,” they wrote, “could result in spillover and establishment of a market cycle while susceptible animals are available to maintain infection.”

What is it that makes this virus unusual? and What have we learned from the SARS experience? One thought that turns up in the latter sort is that “humankind has had a lucky escape.” The scenario could have been very much worse. SARS in 2003 was an outbreak, not a global pandemic. Eight thousand cases are relatively few, for such an explosive infection; 774 people died, not 7 million. Several factors contributed to limiting the scope and the impact of the outbreak, of which humanity’s good luck was only one.

Everything nowadays moves around the planet faster, including viruses. If SARS had conformed to the perverse pattern of presymptomatic infectivity, its 2003 emergence wouldn’t be a case history in good luck and effective outbreak response. It would be a much darker story. The much darker story remains to be told, probably not about this virus but about another. When the Next Big One comes, we can guess, it will likely conform to the same perverse pattern, high infectivity preceding notable symptoms. That will help it to move through cities and airports like an angel of death.

Half a dozen canary fanciers fell ill and, by an account in a Berlin newspaper, “three died in agony.”

“The year 1929 marked a turning point in the revival of interest concerning the etiology of human psittacosis,” according to one historical survey of the disease.

This forthright man, this hands-on administrator, described in one source as “tall with a gnarled Lincolnian face,” was Dr. George W. McCoy. For reasons explicable only in terms of the wonders of the immune system and the vagaries of fortune, Dr. McCoy didn’t get sick. The psittacosis

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.

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,”

“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.

points about Lyme disease emerge plainly. “We know that walking into a small woodlot,” he wrote, “is riskier than walking into a nearby large, extensive forest. We know that hiking in the oak woods two summers after a big acorn year is much riskier than hiking in those same woods after an acorn failure. We know that forests that house many kinds of mammals and birds are safer than those that support fewer kinds. We know that the more opossums and squirrels there are in the woods, the lower the risk of Lyme disease, and we suspect that the same is true of owls, hawks, and weasels.” As for white-tailed deer: They’re involved, yes, but far from paramount, so don’t believe everything you’ve heard.

wind. Both the round bodies of B. burgdorferi and the small form of C. burnetii merely illustrate that, even in the age of antibiotics, bacteria can be sneaky and tough. These microbes remind us that you don’t have to be a virus to cause severe, intractable, mystifying outbreaks of zoonotic disease in the twenty-first century. Although it helps.

Transmission is travel from one host to another, and transmissibility is the packet of attributes for achieving it. Can the virions concentrate themselves in a host’s throat or nasal passages, cause irritation there, and come blasting out on the force of a cough or a sneeze? Once launched into the environment, can they resist desiccation and ultraviolet light for at least a few minutes? Can they invade a new individual by settling onto other mucous membranes—in the nostrils, in the throat, in the eyes—and gaining attachment, cell entry, another round of replication? If so, that virus is highly transmissible. It goes airborne from one host to another.