Spillover: Animal Infections and the Next Human Pandemic

by David Quammen

Coxiella burnetii is an obligate intracellular bacterial pathogen, and is the causative agent of Q fever.[1] The genus Coxiella is morphologically similar to Rickettsia, but with a variety of genetic and physiological differences. C. burnetii is a small Gram-negative, coccobacillary bacterium that is highly resistant to environmental stresses such as high temperature, osmotic pressure, and ultraviolet light. These characteristics are attributed to a small cell variant form of the organism that is part of a biphasic developmental cycle, including a more metabolically and replicatively active large cell variant form.[2] It can survive standard disinfectants, and is resistant to many other environmental changes like those presented in the phagolysosome.[3]

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

an increased density of the susceptible population will facilitate its spread from infected to uninfected individuals.” Increased density: Crowded hosts allow pathogens to thrive.

The Lyme agent, like Coxiella burnetii and Chlamydophila psittaci, is an anomalous, crafty bacterium.

erythema migrans (“spreading redness”)

Borrelia duttonii, which in Africa causes an illness called relapsing fever.

Ixodes scapularis is commonly known as the deer tick or black-legged tick (although some people reserve the latter term for Ixodes pacificus, which is found on the west coast of the USA), and in some parts of the US as the bear tick.[1] It is a hard-bodied tick found in the eastern and northern Midwest of the United States as well as in southeastern Canada. It is a vector for several diseases of animals, including humans (Lyme disease, babesiosis, anaplasmosis, Powassan virus disease, etc.) and is known as the deer tick owing to its habit of parasitizing the white-tailed deer. It is also known to parasitize mice,[2] lizards,[3] migratory birds,[4] etc. especially while the tick is in the larval or nymphal stage.

“Deer ticks” of the species Ixodes scapularis do not draw their crucial sustenance from deer.

Besides being very competent as reservoirs, white-footed mice are also inefficient groomers, poor at clearing off the ticks, which target especially their faces and ears, so that a high percentage of their ticks survive into later stages.

zoonosis may spill over more readily within a disrupted, fragmented ecosystem than within an intact, diverse ecosystem.

In 1846, a Danish physician named Peter Panum witnessed a measles epidemic on the Faroe Islands, a remote archipelago north of Scotland, and drew some keen inferences about how the ailment seemed to pass from person to person, with a delay of about two weeks (what we’d now call an incubation period) between exposure and symptoms.

Robert Koch, who had been a student of Jakob Henle’s at Göttingen, advanced beyond observation and supposition with his experimental work of the 1870s and 1880s, identifying the microbial causes of anthrax, tuberculosis, and cholera. 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,

Macfarlane Burnet, defined a virus as “a piece of bad news wrapped up in a protein.”

Chua’s work established a plausible scenario for spillover. How did the virus go from bats to pigs? All it required was a mango or water apple tree, laden with ripe fruit, overhanging a pigsty. An infected bat feeds on a water apple, discarding the pulp (as bats do), which is besmeared with virus; the pulp drops down among the pigs; one pig snarfs it up and gets a good dose of virus;

replicates in that pig and passes to others; soon the whole herd is infected and human handlers begin to fall sick. It wasn’t a far-fetched scenario. Amid the diversified agriculture of Malaysia at the time, wherein marketable fruit could supplement revenue from livestock, there were more than a few pigsties with mango, water apple, and other fruit trees growing nearby. Nipah virus may have been falling in sweet little packets. What pig could resist?

into the southwestern Bangladesh lowlands. Epstein is a veterinary disease ecologist, based

put the same question—why bats?—to emerging-disease experts around the world. One of them was Charles H. Calisher, an eminent virologist recently retired as professor of microbiology at Colorado State University.

“We oughta write a review paper about bats and their viruses,” he said to Kay Holmes. “This bat coronavirus is really interesting.”

Besides being diverse, bats are very abundant and very social. Many kinds roost in huge aggregations that can include millions of individuals at close quarters.

When a bat lineage split into two new species, their passenger viruses may have split with them, yielding more kinds of virus as well as more kinds of bat. And the abundance of bats, as they gather to roost or to hibernate, may help viruses to persist in such populations, despite acquired immunity in many older individuals.

We’ve gotta grow these bugs the old-fashioned way, we’ve gotta look at them in the flesh, if we’re gonna understand how they operate. And if we don’t, the paper added, “we are simply waiting for the next disastrous zoonotic virus outbreak to occur.”

No one had warned Joosten and Taal about the potential hazards of an African bat cave. They knew nothing of Marburg virus (though they had heard of Ebola). They only stayed in the cave about ten minutes. They saw a python, large and torpid. Then they left, continued their Uganda vacation, visited the mountain gorillas, did a boat trip, and flew back to Amsterdam. Thirteen days after the cave visit, home in Noord-Brabant, Astrid Joosten fell sick.

better care and be isolated from other patients. There she developed a rash and conjunctivitis; she hemorrhaged. She was put into an induced coma, a move dictated by the need to dose her more aggressively with antiviral medicine. Before she lost consciousness, though not long before, Jaap went back into the isolation room, kissed his wife, and said to her, “Well, we’ll see you in a few days.” Blood samples, sent to a lab in Hamburg, confirmed the diagnosis: Marburg. She worsened. As her organs shut down, she lacked for oxygen to the brain, she suffered cerebral edema, and before long Astrid Joosten was declared brain-dead. “They kept her alive for a few more hours, until the family arrived,” Jaap told me. “Then they pulled the plug out and she died within a few minutes.”

Plowright’s project, like much work in ecology these days, entailed a combination of data-gathering from the field and mathematical modeling by computer. The basic conceptual framework, she explained, “was developed by two guys in the 1920s, Kermack and McKendrick.” She meant the SIR model (susceptible-infected-recovered),

metapopulation: a population of populations. The virus avoids extinction by infecting one relatively isolated population of bats after another. It dies out here, it arrives and infects there; it may not be permanently present in any one population but it’s always somewhere.

Now imagine one such bat population within the metapopulation. It has progressed through the SIR sequence, every individual infected, every one recovered, and the virus is gone. But not gone forever. As years pass, as the birth of new bats and the death of old ones raise back the proportion of susceptibles,

The second alert came a month later, again in the CDC newsletter. While Gottlieb was noticing Pneumocystis pneumonia and candidiasis, a New York dermatologist named Alvin E. Friedman-Kien spotted a parallel trend involving a different disease: Kaposi’s sarcoma. A rare form of cancer, not usually too aggressive, Kaposi’s sarcoma was known primarily as an affliction of middle-aged Mediterranean males—the sort of fellows you’d expect to find in an Athens café, drinking coffee and playing dominoes. This cancer often showed itself as purplish nodules in the skin. Within less than three years, Friedman-Kien and his network of colleagues had seen twenty-six cases of Kaposi’s sarcoma in youngish homosexual men. Some of those patients also had Pneumocystis pneumonia. Eight of them died. Hmm. Morbidity and Mortality Weekly Report carried Friedman-Kien’s communication on July 3, 1981.

“You’ve probably never heard of nucleopolyhedroviruses,” Dwyer said to us. The name had changed slightly since 1993 but, thanks to the tent caterpillar episode, and to Judith H. Myers, I had. Dwyer described the devastating effect of NPVs on outbreak populations of forest lepidopterans. He spoke particularly about the gypsy moth (Lymantria dispar), another little brown creature, whose outbreaks and crashes he had studied for twenty years. He said that gypsy moth larvae essentially “melt” when infected by NPV.