Spillover: Animal Infections and the Next Human Pandemic

Quammen next considers where viruses “jump” from, noting that while some come from monkeys, or rodents, bats are a particularly common reservoir host, encompassing diseases like SARS and rabies. Quammen’s next disease exploration, Nipah, also belongs to this group, though it enters humans from pigs that bats have previously infected.

The Nipah outbreak began in Malaysia in 1998 after several people came down with “fever, headache, drowsiness, and convulsions. The victims were pig farmers or somehow associated with pig processing” (314). Health officials assumed the pigs had been infected by mosquitoes and that the disease was Japanese encephalitis (JE). Scientists at in the Department of Medical Microbiology at the University of Malaya became suspicious, though, when most of the cases appeared in adults. The department was led by Dr. Sai Kit Lam, called “Ken” by English speakers. JE was mainly known as a pediatric affliction. The virus also had a higher fatality rate than JE, and Malaysian pigs were suffering more from this disease than they typically did. In pigs, it was airborne, accompanied by “a rolling chorus of porcine hacking—people could hear it coming and wait with dread” (316).

Using samples from patients, scientists at the University of Malaya placed the virus inside a monkey kidney and observed that “the virus in culture started causing damage. The damage didn’t look like JE” (317). The Malaysian scientists lacked an electron microscope for further study, so one colleague, Paul Chua, traveled to a CDC office in Colorado. The team there thought it resembled paramyxovirus but sent him on to Atlanta. The team there found that the virus resembled Hendra but was distinct. It was eventually given a name: “Nipah virus, after that little village of the fifty-one-year-old farmer” who had provided the first tissue samples after his death (318).

When it was clear that the new disease resembled Hendra, Ken Lam called on his Australian colleague Hume Field, who joined an international team including members from the CDC. Their first goal was to slow down the outbreak. They began by visiting pig farms and determined that the virus afflicting those animals matched the human samples. This only established pigs as the amplifier host as horses had been for Hendra, so the search for the reservoir was ongoing.

Public anxiety remained high, and the government ordered the nation’s 1.1 million pigs killed. Some soldiers sent on these operations were infected. The virus was found to be highly contagious among pigs—around 90% showed antibodies when necropsied. The Nipah outbreak is particularly sobering from a public health standpoint, since it highlights that many diseases lurk in the animal agriculture sector, and it’s impossible to predict which may be the “Next Big One” since “we have only begun trying” to identify which viruses animals carry (322).

Hume Field resumed his hunt for the reservoir after three weeks of examining pigs. Field and his team tested many animals and found that several species of bat contained a lot of Nipah antibodies, but they had not yet proven conclusively that this was the reservoir, due to an absence of actual virus. A Malaysian team had more luck establishing flying foxes as the reservoir. Additionally, they found that bats and pigs were likely eating some of the same fruit from a plant known locally as a water apple, which allowed the pigs to become infected and in turn infect humans.

While Malaysia embarked on a Nipah public health campaign that included separating pig habitats from fruit trees, a Nipah outbreak occurred in Bangladesh, home to very few pigs owing to its large Muslim population. Bangladesh is densely populated, so concerns about Nipah spread took on particular urgency. The first two outbreaks in 2001 and 2002 offered few substantive clues. The third, in 2004, killed over a dozen people, mostly teenage boys. The only significant data point a team of epidemiologists discovered was that many of the boys had climbed trees, which are natural bat habitats. Another outbreak occurred in April 2004, and the fifth in four years was in January 2005, raising alarm about a possible epidemic and that conditions in Bangladesh were somehow uniquely hospitable to Nipah.

The investigation centered around the work of a CDC researcher named Stephen Luby, seconded to Dhaka as a program director within the International Center for Diarrheal Disease Research, Bangladesh (ICDDRB). The team conducted interviews with survivors and found that many of them had drunk date palm sap, a “seasonal delicacy” in that part of the country. Quammen personally visited Steve Luby to discuss the Nipah investigation. Luby had eventually decided to focus his medical career on “infectious diseases in low-income countries” and had spent many years in Bangladesh (329). He typically works on diseases like pneumonia that kill far more people but insisted that Nipah was still of concern since in Bangladesh it was spreading from person to person more than it had in Malaysia. There were also global implications, since Bangladesh was the only place where one could consistently study how the virus behaved outside a laboratory.

Luby and his team found that the main fruit bat in Bangladesh eats date palm sap and leaves excrement behind, especially if sap collectors are not overly concerned with the purity of their product. His team focused first on low-cost and humane ways to keep bats away from the harvested sap, but they did not focus on how the virus lived in bats, how spillover occurred, and what was unique about Bangladesh that caused Nipah to spread among people more readily there.

To answer these questions, Quammen worked with a veterinary disease ecologist named Jon Epstein, who also had a master’s in public health. He had found Nipah in Indian bats and also worked on identifying the SARS reservoir. They worked with a Bangladeshi vet named Arif Bangla and another named Jim Desmond. As they left the capital of Dhaka for a city called Khulna, Quammen observed more preparations for harvesting date palm sap. They found a “derelict storage depot” with several large trees nearby and decided this was a promising place to live trap bats to test them for Nipah (337).

Quammen notes the precautions taken—it was imperative not to get bitten as the bats might carry rabies along with Nipah. There was an assigned uniform for this: “Epstein issued respirator masks, safety goggles, and medical gloves (not latex, not rubber, but the latest material of choice: nitrile) to everyone, and we suited up” (340). That night, on the roof of the building, the team set up an invisible mesh net to catch the bats as they returned from a night’s feeding. They caught six and released them after taking samples.

Sharing his thoughts on ecology and zoonosis, Epstein highlighted humanity’s role in outbreaks: “It’s a matter of contact with humans, interaction, opportunity. ‘Therein lies the risk of spillover’” (343). Humans offer a “wealth of opportunity” since they remain present after disrupting the habitat of a traditional viral host (343).

Zoonotic disease, then, happens because ecological disruption intersects with a process over which humans have no control: viral evolution. This is also not an emotional or deliberate process. Epstein underlined this: “Don’t imagine that these viruses have a deliberate strategy, he said. Don’t think that they bear some malign onus against humans. ‘It’s all about opportunity’” (345).

Quammen visits virologist Charlie Calisher to understand why one theme kept coming up in his travels and research: Why is so much spillover traceable to bats? Calisher became interested in the subject after the 2004 SARS outbreak, suggesting that he and a colleague who specialized in coronaviruses investigate “bats and their viruses” (347). After talking with an immunologist colleague, the three friends discovered they knew nothing about the subject, and little had been published. To compensate for their knowledge gap, they enlisted an epidemiologist along with Australian expert Hume Field.

The resulting paper was meant only as a “review” to gather existing knowledge and trends and offer suggestions for further study. It was published as “Bats: Important Reservoir Hosts of Emerging Viruses” (348) and quickly gained wider traction in the scientific community. The paper made several points—first, bats represent about one in four mammals, so it is possible that their role in zoonosis is commensurate with their global population.

Bats are also an older mammal, having had plenty of time to evolve along with viruses. They are also social, which may help viruses continue to maintain a “critical community size” of infected animals (349). In viruses that can persist in a host, the long lifespan of the animal is another advantage. Bats also live in crowded conditions, which makes spreading disease straightforward. Another influential factor is flight: Bats are present on a wider geographic scale than many other mammals. Calisher’s most persistent point was that viruses had to be studied in animals and not just sequenced in laboratories—only this work could explain what factors in a bat immune system might be particularly hospitable to viruses.

At the time Calisher’s paper was written, bats were a tentatively identified reservoir host for two other viruses: Marburg and Ebola. Conclusive proof about Marburg’s nature arose after an outbreak among miners in Uganda in 2007. An international response team quickly arrived at Kitaka cave, prepared for underground sampling of animals based on suspicions from previous outbreaks. The cave was home to a large number of fruit bats, of which the team collected about eight hundred. The team returned seven months later, since the presence of Marburg after an outbreak would help confirm the reservoir hypothesis. They conducted a trap and release operation and released 1,329 tagged animals. Ultimately, the team found Marburg antibodies, some RNA, and, through lab work in BSL-4 conditions, proof of live virus.

In 2008, a Dutch business analyst named Astrid Joosten went to Uganda on vacation with her husband. They toured a cave in the Maragambo Forest; about 30 miles from the Kitaka mine, it was covered in bat guano. Thirteen days later, Astrid Joosten got sick, and her doctors suspected Marburg. She was “the first person known to have left Africa with an active filovirus infection and died” (359), while her husband never developed symptoms.

A business analyst named Michelle Barnes recognized herself when Astrid’s story made the news, and she met with Quammen to describe her experiences as a Marburg survivor. As part of a Uganda tour in Queen Elizabeth National Park, Barnes and her husband also detoured to a cave. Back home in the US, she fell ill and was eventually hospitalized in organ failure and nearly died, but she left the hospital after 12 days, still undiagnosed as an initial Marburg test came back negative. After reading about Astrid, Michelle pushed her doctor to send her samples to the CDC, and she successfully “self-diagnosed.”

Astrid’s case resulted in another journey for an international response team, since the infection of tourists meant that Marburg could be “an international threat” (364). During their cave expedition, Jonathan Towner found one of the bats tagged in Kitaka cave, proving that infected bats were traveling. This led scientists, and Quammen, to another question: Why is there not more spillover? Why has Marburg not “gone global?”

To answer this question, Quammen returned to Australia to speak with a veterinarian turned infectious disease ecologist named Raina Plowright, who was studying Hendra for her dissertation project. She noted that between 1997 and 1998, four viruses had emerged from one species of bat, including Nipah and Hendra. Plowright was looking into what ecological changes could have led to Hendra’s emergence.

To do this, she turned back to earlier mathematical models that consider the number of susceptible, infected, and recovered animals. Bat infections are compared to a sequence of Christmas lights—when populations are distant from one another, the disease is always “somewhere,” but as it is never anywhere for long, it runs out of vulnerable bats to infect. After more “susceptibles” are born, outbreaks recur, and they are more “explosive” as the number of possible cases is larger. Plowright’s model also described the situation for bats in Australia—rapid deforestation meant that bat populations now lived much further from each other and much closer to humans—which led Quammen to speculate that this explained a “greater likelihood of spillover into another species” (369).

To conclude his discussion, Quammen turns back to the mystery of Ebola’s reservoir, describing “detective work” conducted by Eric Leroy’s team in the Democratic Republic of the Congo. An outbreak from May to November of 2007 was their primary concern. It was traced to a single woman, and ultimately more than 200 people were infected. Leroy and his team began to consider the story of “Patient A” and how her activity might shed light on the virus. They learned that a nearby village was home to both a large market and a large number of bats.

One man suffered a mild case of Ebola, likely from purchasing bats to eat at the market, and his daughter also died. “Patient A” was a family friend who had closely participated in funeral preparations, including washing the body. Leroy turned to another mystery—it seemed likely that lone individuals had been infected, since so many people in the area ate bats; why had this not led to an outbreak? Quammen returns to his time in Bangladesh, describing the case of one Nipah superspreader: A local religious leader became infected, and many of his followers had likely touched him, as was customary in the culture when people became ill. The man had also coughed often, and hand washing was not common practice.

Quammen turns to ICDDRB, known locally as the “cholera hospital” (379), where he saw many people sick with routine but devastating illness, like cholera and dysentery. He found himself mistaken for a doctor and yet helpless to assist anyone. This led him to a question that is both scientific and philosophical. In a world where routine health crises sicken and kill so many, why study relatively obscure cases of zoonosis? Quammen comes back with a one-word answer, his next disease subject: “AIDS.”