Spillover: Animal Infections and the Next Human Pandemic

by David Quammen

zoonosis is an animal infection transmissible to humans.

African horse sickness (AHS), a disease carried by biting midges in sub-Saharan Africa. AHS virus affects mules, donkeys, and zebras as well as horses,

When a pathogen leaps from some nonhuman animal into a person, and succeeds there in establishing itself as an infectious presence, sometimes causing illness or death, the result is a zoonosis.

Ebola is a zoonosis. So is bubonic plague. So was the so-called Spanish influenza of 1918–1919, which had its ultimate source in a wild aquatic bird and, after passing through some combination of domesticated animals (a duck in southern China, a sow in Iowa?) emerged to kill as many as 50 million people before receding into obscurity. 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.

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.

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.

An amplifier host is a creature in which a virus or other pathogen replicates—and from which it spews—with extraordinary abundance.

not just Machupo but also Marburg (1967), Lassa (1969), Ebola (1976, with Karl Johnson again prominently involved), HIV-1 (inferred in 1981, first isolated in 1983), HIV-2 (1986), Sin Nombre (1993), Hendra (1994), avian flu (1997), Nipah (1998), West Nile (1999), SARS (2003), and the much feared but anticlimactic swine flu of 2009.

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.

It’s not that they target us especially. It’s that we are so obtrusively, abundantly available. “If you look at the world from the point of view of a hungry virus,” the historian William H. McNeill has noted, “or even a bacterium—we offer a magnificent feeding ground with all our billions of human bodies, where, in the very recent past, there were only half as many people. In some 25 or 27 years, we have doubled in number. A marvelous target for any organism that can adapt itself to invading us.”

There’s no reason to assume that AIDS will stand unique, in our time, as the only such global disaster caused by a strange microbe emerging from some other animal.

The bacterium now called Legionella pneumophila emerged from the cooling tower of an air-conditioning system at a hotel in Philadelphia, in 1976, to create the first-known outbreak of Legionnaires’ disease and kill thirty-four people.

The famous mountain gorillas, for instance, have been threatened by anthroponotic infections such as measles, carried by ecotourists who come to dote upon them.

the list of major symptoms of Ebola virus disease goes like this: abdominal pain, fever, headache, sore throat, nausea and vomiting, loss of appetite, arthralgia (joint pain), myalgia (muscle pain), asthenia (weakness), tachypnea (rapid breathing), conjunctival injection, and diarrhea.

BSL-4 is reserved for work on pathogens such as Ebola, Marburg, Nipah, Machupo, and Hendra, for which there are neither vaccines nor treatments.)

Rheumatoid arthritis is an immune dysfunction, and the medicine used to control it can potentially suppress normal immune responses.

Christiaan Huygens proposed that light consists of waves, whereas Isaac Newton argued that light is particulate.

plague in London (1665), measles in Glasgow (1808), cholera in London (1832), scarlet fever in Halifax (1880), influenza in London (1891),

anyone who favors Intelligent Design in lieu of evolution might pause to wonder why God devoted so much of His intelligence to designing malarial parasites.

They found that western gorillas carry a high prevalence of plasmodium (about 37 percent of the population is infected) and that some of those gorilla parasites are nearly identical to P. falciparum. “This indicates,” they wrote confidently, “that human P. falciparum is of gorilla origin, and not of chimpanzee, bonobo or ancient human origin.”

The human version is one twig within a gorilla branch, suggesting that it came from a single spillover. That’s one mosquito biting one infected gorilla, becoming a carrier, and then biting one human. By delivering the parasite into a new host, that second bite was enough to account for a zoonosis that still kills more than a half million people each year.

Syphilis is caused by a spiral bacterium (aka a spirochete) known as Treponema pallidum. The bacterium is usually acquired during sexual contact, whereupon it corkscrews its way across mucous membranes, multiplies in the blood and lymph nodes, and, if a patient is especially unlucky, gets into the central nervous system, including the brain, causing personality change, psychosis, depression, dementia, and death.

it is possible that we are setting the stage for a switch of host for P. knowlesi, similar to the one postulated for P. vivax.” A host switch, they meant, from macaques to humans.

February 2003, SARS got on a plane in Hong Kong and went to Toronto. Its arrival in Canada was unheralded but then, within days, it began to make itself felt. It killed the seventy-eight-year-old grandmother who had carried it into the country, killed her grown son a week later, and spread through the hospital where the son had received treatment. Rather quickly it infected several hundred other Toronto residents, of whom thirty-one eventually died.

Singapore became another epicenter. In Hanoi, a Chinese American businessman who brought his infection from Hong Kong became ill enough to merit examination by Dr. Carlo Urbani, an Italian parasitologist and communicable-diseases expert stationed there for the World Health Organization. Within ten days the businessman was dead; within a month, Dr. Urbani was too. Urbani died at a hospital in Bangkok, having flown over for a parasitology conference in which he was never able to take part. His death, because of his much-admired work within WHO, became a signal instance of what emerged as a larger pattern: high rates of infection, and high lethality, among medical professionals exposed to this new disease, which seemed to flourish in hospitals

Flight CA112 took off from Hong Kong that day carrying 120 people, including a feverish man with a worsening cough. By the time it landed in Beijing, three hours later, twenty-two other passengers and two crewmembers had received infectious doses of the coughing man’s germs. From them it spread through more than seventy hospitals just in Beijing—yes, seventy—infecting almost four hundred health-care workers as well as other patients and their visitors.

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.”

Hong Kong wasn’t the origin of SARS, merely the gateway for its international dispersal . . . and very close to its origin. The whole phenomenon had begun quietly, several months earlier, in the southernmost province of mainland China, Guangdong, a place of thriving commerce and distinctive culinary practices,

On November 16, 2002, a forty-six-year-old man in Foshan came down with fever and respiratory distress. He was the first case of this new thing,

Symptoms included headache, high fever, chills, body aches, severe and persistent coughing, coughing up bloody phlegm, and progressive destruction of the lungs, which tended to stiffen and fill with fluid, causing oxygen deprivation that in some cases led to organ failure and death.

This seafood merchant was a man named Zhou Zuofeng. He holds the distinction of being the first “superspreader” of the SARS epidemic. A superspreader is a patient who, for one reason or another, directly infects far more people than does the typical infected patient. While 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.

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.

twenty-three doctors and nurses became infected from Zhou, plus eighteen other patients and their relatives. Nineteen members of his own family also got sick. Zhou himself would eventually become known among medical staff in Guangzhou as the Poison King. He survived the illness, though many people who caught it from him—directly, or indirectly down a long chain of contacts—did not.

One of those secondary cases was a sixty-four-year-old physician named Liu Jianlun, a professor of nephrology at the teaching hospital where Zhou had first been treated. Professor Liu began feeling flulike symptoms on February 15, two weeks after his exposure to Zhou, and then seemed to get better—well enough, he thought, to follow through on plans to attend his nephew’s wedding in Hong Kong. He and his wife took the three-hour bus ride from Guangzhou on February 21, crossed the border, spent an evening with family, and then checked into a large, midrange hotel called the Metropole, favored by businessmen and tourists, in the Kowloon district of Hong Kong. They were given room 911, across from the elevators in the middle of a long corridor, a fact that became central to later epidemiological investigations. Two fateful things happened that night at the Metropole Hotel. The professor’s condition worsened; and at some point he seems to have sneezed, coughed, or (depending on which account you believe) vomited in the ninth-floor corridor. In any case, he shed a sizable dose of the pathogen that was making him sick—enough to infect at least sixteen other guests and a visitor to the hotel. Professor Liu thereby became the second known superspreader of the epidemic.

She recollected that the cardiologist, a pregnant woman, had worn a mask while performing the intubation, and though that doctor got ill afterward, she recovered. The resident, standing nearby, had worn no mask. “It was a guy. He was sick for a while and brought it home. His mother,” Ang said. “His own mother nursed him and she became sick.” “Did they survive?” “No.” “Neither one of them,” I said. “It was one of the most painful things. Because he was a young, twenty-seven-year-old doctor. And his mother also died.”

By the middle of July, when the last SARS patient left Tan Tock Seng Hospital, more than two hundred cases had been recognized. Thirty-three of those people died, among whom were Esther Mok’s father, her pastor, her mother, and her uncle, in that order of demise. Esther herself survived.

To establish causality, Peiris’s team tested blood serum from SARS patients (because it would contain antibodies) against the newfound virus in culture. This was like splashing holy water at a witch. The antibodies recognized the virus and reacted strongly. Less than a month later, based on that evidence plus other confirming tests, Malik Peiris and his colleagues published a paper cautiously announcing this new coronavirus as “a possible cause” of SARS.

Between late 2000 and early 2003, a team of researchers based in Hong Kong conducted an ongoing survey of wild animals on sale at Chatou, Dongmen, and two other big Guangdong markets. Compared to an earlier survey done in 1993–1994, the team found some changes and new trends. First, the sheer volume of the wild-animal trade seemed to have increased. Second, there was more cross-border commerce, legal or covert, drawing wildlife from other Southeast Asian countries into southern China. Meaty but precious individuals of endangered species, such as the Bornean river turtle and the Burmese star tortoise, were turning up. Third, greater numbers of captive-bred animals had become available from commercial breeders.

By the time that paper appeared, the SARS epidemic of 2003 had been stopped, with the final toll at 8,098 people infected, of whom 774 died. The last case was detected and isolated in Taiwan on June 15.

Their sampling showed that this SARS-like virus was especially prevalent in several bats belonging to the genus Rhinolophus, known commonly as horseshoe bats.

At the Chatou market in Guangzhou, for instance, he had seen storks, seagulls, herons, cranes, deer, alligators, crocodiles, wild pigs, raccoon dogs, flying squirrels, many snakes and turtles, many frogs, as well as domestic dogs and cats, all on sale as food. There were no civets, not when he saw the place; they had already been demonized and purged.

You could also buy leopard cat, Chinese muntjac, Siberian weasel, Eurasian badger, Chinese bamboo rat, butterfly lizard, and Chinese toad, plus a long list of other reptiles, amphibians, and mammals, including two kinds of fruit bat.

I had begun to see Aleksei’s point: If you’re a carnivore, you’re a carnivore, so what’s the merit of fine distinctions?

“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.

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.

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.

environmental disruption by humans as a releaser of epidemics.

“I would feel a lot more comfortable,” Ostfeld answered, “if I knew that the landscape would support healthy populations of owls, foxes, hawks, weasels, squirrels of various kinds—the components of the community that could regulate mouse populations.” In other words, biological diversity. This was his offhand way of expressing the most notable conclusion that has emerged from twenty years of research: Risk of Lyme disease seems to go up as the roster of native animals, in a given area, goes down.

Some people take “All life is connected” to be the central truth of ecology, Ostfeld added. It’s not. It’s just a vague truism. The real point of the science is understanding which creatures are more intimately connected than others, and how, and to what result when change or disturbance occurs.

Koch’s discoveries, along with those of Pasteur and Joseph Lister and William Roberts and John Burdon Sanderson and others, provided the empirical bases for a swirl of late-nineteenth-century ideas that commonly get lumped as “the germ theory” of disease, which marked a movement away from older notions of malign vapors, transmissible poisons, imbalanced humors, contagious putrefaction, and magic.