Nadia began coughing on March 27. The 4-year-old Malayan tiger's keepers at the Bronx Zoo in New York City also noticed she wasn't finishing her daily allotment of raw meat. Concerned, they called in Paul Calle, the zoo's head veterinarian.
The team immobilized and anesthetized Nadia, so she could be put through a series of X-rays, ultrasounds, and routine blood work to look for known causes of respiratory disease in cats. "Since New York City is the epicenter for Covid in the U.S.," said Calle, "we wanted to make sure we checked her for that, too."
On April 5, the zoo reported that Nadia had been infected by SARS-CoV-2, the virus that causes Covid-19. Over the course of the next week, three other tigers and three lions at the zoo also began showing similar symptoms. The sick cats were later tested, along with another 8-year-old male Amur tiger named Alden, who hadn't been showing any symptoms. Every test came back positive, according to a statement released by the zoo on April 22. All eight cats are now recovering well, and "only an occasional cough is heard," Calle said.
Officials think that an asymptomatic zoo worker carrying the virus probably infected the animals. "People and animals and the environment are all closely linked and influence what happens to each other," said Calle.
This is far from the first time, and certainly won't be the last, that an infectious disease has bounced between humans and other animals. Evidence suggests that Covid-19 likely originated in a bat, possibly jumped to a pangolin — which looks like a scaly anteater — and then infected a human, maybe at a live animal market in Wuhan, China. Globally, an estimated 75 percent of newly appearing infectious diseases are "zoonotic" like this, meaning they can pass from non-human animals to people. Infectious-disease experts warn that nature harbors more than a million undiscovered viruses.
The animals we keep as pets can be part of the transmission process, too. Exotic pet rodents were implicated as the likely source of an outbreak of monkeypox in the Midwest in 2003. Pigs, obviously, spawned the 2009 swine flu pandemic. And, last month, the U.S. Centers for Disease Control and Prevention and the Department of Agriculture confirmed that two pet cats in New York had tested positive for SARS-CoV-2. A pug in North Carolina named Winston was also added to the list in late April.
Recognition of the link between humans and other animals for Covid-19 is driving the push to ban China's live animal markets, which pose a high risk for contagion. And animal health expertise could help prevent outbreaks in other ways, some scientists say. For example, greater animal surveillance could detect new diseases earlier and stop them from being passed to humans. And techniques for controlling outbreaks in livestock, such as randomized surveillance strategies, could also improve efforts to limit the spread of disease in human populations.
Yet despite being recognized as useful, the field of animal health has long been siloed away from human medicine. Veterinarians as well as wildlife biologists, livestock farmers, and zookeepers remain a largely untapped resource for combatting diseases that threaten people. "There is still a very traditional divide among disciplines," said Jon Epstein, a wildlife veterinarian and disease ecologist for the EcoHealth Alliance in New York. "We haven't removed these barriers yet."
That's not to say that experts haven't been trying. But progress in getting authorities to see the connectedness of human and animal health has been slow — and in some instances in recent decades, has even gone backwards.
"It's time that we stopped using humans as sentinels of animal diseases," said Joe Annelli, the executive vice president of the National Association of Federal Veterinarians and formerly with the USDA. Instead, he said, we should be aiming to identify diseases in other animals as early as possible, when there's still a chance of preventing them from spreading to humans.
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Nearly 20 years ago, the Bronx Zoo was in the spotlight as another contagion crept among the city's people and non-human animals.
It was the summer of 1999, and a strange disease that caused weakness and confusion had begun popping up among dozens of New Yorkers. Meanwhile, dead crows had started landing on the zoo's grounds. Then came casualties among captive species: Chilean flamingos, laughing gulls, a snowy owl, and a bald eagle named Clementine.
Clementine was the zoo's mascot. "She looked perfectly fine and then, boom, she dropped dead," said Tracey McNamara, then the chief veterinary pathologist at the zoo. Her necropsy of Clementine — standard procedure for any death at an accredited zoo in the U.S. — showed the worst brain inflammation in a bird that McNamara had ever seen. Worried that her surgical mask wasn't enough protection against whatever had killed the eagle, McNamara went home that night and wrote her will.
She also went on with her detective work, taking advantage of what she called "built-in sentinels" of disease naturally found at a zoo. The CDC, at the time, suspected a brain disease called Saint Louis encephalitis. But McNamara knew that this disease doesn't typically harm birds. Inflammation in bird brains, she noted, instead suggested one of three usual suspects in the U.S. The first was eastern equine encephalitis. Emus are known to be particularly sensitive to this virus, yet the zoo's emu flock showed no signs of sickness. That left the other two possibilities: virulent Newcastle disease and highly pathogenic avian influenza. Both of these affect chickens, and the petting zoo was full of healthy birds.
"That's when I knew I was dealing with something unknown to veterinary medicine," said McNamara, now a professor of pathology at Western University of Health Sciences in Pomona, California.
While the CDC initially dismissed McNamara's suggestion that the same disease might be impacting both people and birds, the agency eventually came around. Tests weeks later revealed that New York was home to the first cases of West Nile virus ever reported in the Western hemisphere. And, as the U.S. General Accounting Office would report in September 2000, the animal infections preceded the first human cases by at least one or two months. "The West Nile events illustrate the value of communication between public and animal health communities," the GAO wrote.
As this mosquito-borne disease swept from New York across the U.S., none of the traditional means of surveillance — tests of mosquito pools or chicken flocks — proved to be predictive of human risks. So McNamara pushed for the launch of a nationwide surveillance network across zoos, suggesting it could bolster the CDC's power to prevent outbreaks. The agency was convinced. The zoo network went live and, between 2001 and 2006, nearly 180 zoos and other wildlife institutions submitted samples.
"We hoped that this was the beginning of sustainable zoonotic disease surveillance in urban centers," said McNamara. "Every major city has a zoo. Every zoo has a spectrum of the animal kingdom, some of which are guaranteed to be susceptible to whatever new virus pops up."
But efforts to secure continued funding — let alone money to expand the program beyond West Nile virus — were all denied.
Donald Noah, a veterinary epidemiologist at Lincoln Memorial University in Harrogate, Tennessee, was working with the U.S. Department of Homeland Security when McNamara's team reached out to his agency for financial support. He lamented not being able to convince senior leadership to oblige. "Hopefully, given the situation now, there is a change in awareness and more realization of the importance," Noah said.
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Pets, wildlife, livestock, and zoo animals can all serve as early warning signs of an emergent threat to humans. When wildlife biologists notice squirrels lying around dead, for example, it could be an indication of the plague. "Whether it is plague or hantavirus or rabies — or now Covid-19 — viruses may be circulating for an unknown period of time in an animal reservoir species and then all of a sudden became apparent in humans," said Noah.
Spotting signs of disease in bats or an intermediary animal, such as pangolins, may have warned officials of the threat of Covid-19 before it went pandemic, noted Victoria Brookes, a zoonotic disease expert at Charles Sturt University in Wagga Wagga, Australia.
"We're always looking at timeliness," said Brookes, who is helping to launch a "disease detective" training program for animal workers across Southeast Asia and Oceania that will support the development of local surveillance systems to detect diseases before they spawn an outbreak.
Annelli underscored the need for such surveillance: "We put all this money and work into identifying the first person to have a particular disease, but we've spent nothing on identifying that disease in the animal population and working to eliminate it before it continues to infect people," he said.
But if a sick animal is not of economic value, then testing for and reporting any illness remains especially difficult. "There is still no federal agency that has jurisdiction over surveillance of zoo animals, or dogs and cats," added McNamara. "We have a gigantic species gap in our biosurveillance efforts in the U.S."
For instance, towards the end of 2016, at an animal shelter in East Harlem about 6 miles from the Bronx Zoo, an orange-and-white cat named Mimi developed a respiratory infection, became very sick, and had to be euthanized. Cats in multiple other crowded New York shelters started falling ill over the following weeks. An attending veterinarian got sick as well.
The culprit turned out to be a strain of bird flu, H7N2, never before seen in cats. By the time a private foundation stepped in to cover the costs of testing and quarantining the potentially affected animals, about 1,000 felines had already been adopted out to families throughout the greater metropolitan area.
Sandra Newbury, director of the Shelter Medicine Program at the University of Wisconsin-Madison, worked with the shelters to contain the virus. Thanks to the private donor, they were able to offer free testing and medical care for the adopted cats, eventually isolating hundreds that had been infected. "We were really aggressive in our efforts to not let it spread," Newbury said. She believes identifying such a large number of infected animals and quarantining them allowed the authorities to eradicate the virus. According to Newbury, no positive tests have been reported since March 2017.
"We were really very lucky. This could've turned into a new virus of cats," said Newbury, noting the contrast with what's playing out today. "A virus spreads more easily when you don't know that it's there. That's what we're seeing now with Covid-19 in humans. There's not enough testing."
While it would be impossible to identify every possible disease in non-human animals, noted Annelli, far more could be done to test for diseases known to occasionally spill over to humans, such as Ebola. He also believes we should be regularly sampling animals at live markets for influenza and coronaviruses, and testing wildlife in natural areas where they might closely overlap with domestic animals and people — such as deforested lands — to see how diseases evolve over time. The commingling of species provides an optimal environment for viruses to mutate to the point that they could infect people.
"When multiple species are mixed together that are not usually next to each other, then you can get all kinds of things popping up," said Annelli. The 2003 monkeypox outbreak is another case in point: Gambian rats caught in Africa were shipped to the U.S. and ended up being housed next to prairie dogs, a species they had never been in close contact with in the wild. Once infected, prairie dogs can fairly easily transmit the virus to people. And evidence suggests they did.
Experts underscore the importance of finding not only the species that spread viruses in the first place, but also which animals may maintain them in the future. Even if control measures manage to curb Covid-19 in human populations, for example, might the virus simply hide out in domestic cats, local bats, or another non-human species, ready to re-emerge later? "That's an open question that needs to be examined," said Epstein.
A Chinese study published in March identified several species that SARS-CoV-2 might be able to infect, including cats, cows, pigeons, and pangolins. Another study underway in Germany is exposing different animals to the virus in hopes of deciphering whether it could infect as well as replicate within certain species — and so potentially sustain itself there. Early findings reported in April suggest that fruit bats and ferrets are susceptible, while pigs and chickens are not.
But just because an animal can be infected doesn't necessarily mean it can spread the disease to others. Thankfully, the flu that affected the shelter cats turned out to be fairly mild and minimally transmissible to humans. "If this virus had been as dangerous and as virulent as the pandemic flu of 1918, then the battle would have already been lost," said McNamara.
"We dodged a bullet, she added. "But there's no guarantee we'll be as lucky the next time."
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In 2007, the bluetongue virus — a disease spread by midge bites — began to sweep through herds of sheep and cattle across Europe. Johanne Ellis-Iversen was serving as the veterinary adviser for the U.K.'s Department for Environment, Food, and Rural Affairs towards the end of the outbreak and as it was officially declared over in 2011. The U.K. has seen a number of major outbreaks of disease in food animals in recent decades, including bovine spongiform encephalopathy (aka "mad cow disease") and foot-and-mouth disease. As a result, said Ellis-Iversen, it has a very structured and effective response for fighting epidemics among livestock.
In agricultural animal health, "outbreaks of exotic disease in well-regulated countries rarely get big because we identify and control them right away," said Ellis-Iversen, now a senior adviser and veterinary epidemiologist at the National Food Institute at the Technical University of Denmark. She is also the co-author of a paper published in late March that describes how veterinary surveillance methods could be adapted to randomly survey human populations for Covid-19.
When dealing with infection among livestock, before a decision is made to lift control measures or reopen exports, it's standard procedure to test animals at random to estimate the disease spread. Ellis-Iversen's team did just that to prove the country was free of bluetongue. "We want to know what is happening in a population, not just the herds identified as ill," she said.
In the case of Covid-19, some countries and U.S. states have begun lifting social distancing and containment measures. Their typical plan: Keep an eye out for the re-emergence of infections and then re-enact control measures as necessary. But Ellis-Iversen cautions that if you only pick up infections by testing individuals admitted to hospital or by measuring deaths, then you miss a lot of valuable information — conducting monitoring so far down the line means anything done in response will have a delayed impact. "If officials see that hospital cases are creeping towards a threshold, then it would be another week or two before they can actually reduce the number going into the hospital," she said.
"We're wondering why public health isn't looking more to using the experience from animal health," added Ellis-Iversen. Representative surveys of the population — like those used for livestock — could inform policy making, including outbreak control and exit strategies, she said.
While randomized surveys are not a replacement for other public health tools, such as identifying people who are ill and tracing who they might have infected, Ellis-Iversen believes they could provide some "extremely useful" data for deciding on control measures. Recognizing that some countries have limited testing capacity, she also notes that samples need not be large to provide valuable information. "You don't need to test 10,000 people," said Ellis-Iversen. "We just need to consider how we select the people we test."
Germany is using just such a technique for human populations right now, in the hope that the data will inform what restrictions can be loosened without a resurgence of infections. Ellis-Iversen suggests that while randomized surveys are "used occasionally in public health," they tend to be conducted more for studies rather than as ongoing surveillance for decision making. "It will be interesting to see the results," said Ellis-Iversen. "If they show something unexpected, I am sure it will be food for thought around the world."
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Days before Nadia, the Bronx Zoo tiger, was diagnosed with Covid-19, the Wildlife Conservation Society issued a statement urging the closure of live animal markets. The international organization, which happens to be based at the Bronx Zoo, is among several environmental groups, politicians, and celebrities now advocating for a ban. Live animal markets were also implicated in the 2003 SARS outbreak.
"These emerging infectious diseases from animals are usually resulting from wildlife consumption and distribution on a commercial scale," said Calle, the Bronx Zoo veterinarian. "It's not a lone person hunting to feed their family. It's markets and global supply chains, and encroachment on natural areas, that are the risk factors."
Calle was also a veterinarian at the zoo during the West Nile virus outbreak. He's seen a lot of growth over the last 20 years in terms of looking beyond human medicine to support public health. "There was not the same level of integration and coordination then that there is now," he said.
About a decade ago, awareness of the interconnectedness of humans, other animals, and the environment began to ramp up — even reaching Hollywood. At the end of the 2011 film "Contagion" (which has enjoyed renewed popularity recently thanks to the pandemic), a flashback details the origins of the fictitious virus MEV-1, modeled after the real-life Nipah virus: A bulldozer clears a patch of trees and a displaced disease-carrying bat drops a chunk of banana into a pig farm. Viewers then watch a pig gobble up the fruit before being slaughtered and handled by a chef, who does not wash his hands before greeting Gwyneth Paltrow.
Around the same time as the movie's release, a movement called One Health also emerged. In 2010, the World Health Organization, Food and Agriculture Organization, and the World Organization for Animal Health created a One Health collaboration they termed Tripartite; the CDC established its One Health Office in 2009.
Casey Barton Behravesh, director of the CDC office, highlights the collaboration between city, state, and federal officials in diagnosing Nadia as evidence of progress. "There's definitely more to be done," she said. "Historically, limited resources have been available for needed One Health activities."
Other health experts, too, argue that current efforts don't go far enough. "You can create One Health offices, but achieving any real coordination or integration is tough," said Epstein. "Each agency has its mandate, and it's hard to pay to attention to everything else."
Dirk Pfeiffer, a professor of One Health at the City University of Hong Kong, added that the concept should also go further to include the social sciences. "If you want to control diseases, it's the human behavior that you have to change or influence," he said.
Simply closing down live animal markets could backfire, for example. "As long as there is still a demand, they'll find a way of trading this stuff and then you won't even know how to find it," added Pfeiffer.
Behavioral and cultural practices were at the core of Predict, a project the U.S. Agency for International Development launched in 2009. Working with partners in dozens of countries, the project aimed to bolster the world's ability to identify viruses with pandemic potential. That effort included investigating the human behaviors and practices, as well as ecological and biological factors, that drive the emergence, transmission and spread of diseases.
Funding for the project ended in September 2019, just before Covid-19 emerged.
It's not just at urban food markets where diseases spill over from animals into humans, said Epstein. Hunting or agricultural areas are among other hotspots, especially as humans increasingly encroach on wildlife habitats. "We need to be able to continue this kind of surveillance work — recognize where a spillover is likely to happen, then work with communities and governments to reduce that risk," he added, referring to the efforts launched via Predict. "The U.S. and global community has to commit to investing in a much bigger way. A lack of investment is what has gotten us to where we are now with Covid-19."
Some politicians seem to be getting the message. One Health-related legislation is currently pending in Congress. The Advancing Emergency Preparedness Through One Health Act seeks to improve public health preparedness by requiring federal agencies to develop a One Health approach. Sen. Dianne Feinstein (D-Calif.) is a co-sponsor of the Senate bill. She also spearheaded, alongside Martha McSally (R-Ariz.), a bipartisan resolution for a National One Health Awareness Month, which passed the Senate in December, and is now calling for the creation of a new interagency government entity, the Center for Combating Infectious Disease, "to oversee all aspects of preventing, detecting, monitoring, and responding to major outbreaks such as coronavirus," she told Undark in an email.
"As the planet's climate continues to warm and humans and wild animals migrate in ways that bring them into greater contact, the potential for new pandemics that spread from animals to humans will also increase," added Feinstein. Covid-19, she noted, "has highlighted the interactions of animals and people and the consequences of not monitoring those interactions closely."