An elegant way to stop deadly Hendra virus spillovers from bats to horses ... to us

Not quite 20 years ago, Raina Plowright stood in a forest in Australia's Northern Territory at dusk. She watched as hundreds of thousands of bats called little red flying foxes launched themselves into the air.

"The sky was [dark] with these huge bats taking off in this stream of animals across the landscape looking for nectar," Plowright says. "So just a deafening roar of bat sound, talking to each other, screeching at each other."

Plowright, a disease ecologist at Cornell University who studies pandemic prevention, was interested in bats because they carry a virus called Hendra. And while it's harmless to bats, they can pass it to horses through their feces and urine.

For equines it manifests as a nasty respiratory and neurological disease. They can develop a frothy nasal discharge, trouble breathing and odd behaviors, like drinking water constantly or throwing themselves against the wall of a stable. The virus kills three out of every four horses it infects. Over 100 horses have died from Hendra, though there are no known cases at the moment.

And it's not just a problem for horses. "When people treat sick horses," says Plowright, "that's when people get sick. That's when people get Hendra virus."

Fortunately, Hendra doesn't spread easily among humans. There have only been seven documented cases, but four of them were lethal. And each time a virus jumps from animals to humans — in this case, from bat to horse to person — it gets another chance at evolving and becoming more infectious.

With such a severe human fatality rate, the possibility of an outbreak could be devastating. "I mean, we're talking about a catastrophic, civilization-changing event," Plowright says.

But there are signs that Hendra can be tamed. "More recently, anyone with significant exposure to Hendra virus has been treated with monoclonal antibodies and so they have not become infected," she says.

Her mission: Find out what makes Hendra spill over

Hendra — named for a suburb of Brisbane, Australia where the virus once killed a number of racehorses — is what had brought Plowright to the country. She wanted to understand the conditions that made it more likely for the virus to move from bats into horses, an occurrence that's detected relatively rarely. If she could understand that, she figured she might be able to head off spillovers before they happened. (And she hopes that her findings might apply to other diseases besides Hendra. Bats harbor tons of viruses. For instance, many scientists agree that SARS-CoV-2 spilled over into humans from an animal, maybe a bat.)

The first step was for Plowright to capture little red flying foxes to see how many had the Hendra virus and how that number changed over time. Every three months, Plowright and her team would string up nets along the riverbanks for a two-week stretch, hoping to catch bats ... while keeping an eye out for crocodiles.

"The crocodiles are really smart," says Plowright. "They actually learn your behavior. So we'd have to move our nets every day so that the crocodiles wouldn't learn where we were. The viruses certainly weren't the most dangerous part of the work."

Once the bats were in hand, Plowright sampled their blood. "And what we noticed is there was usually very little virus," she says. "We often couldn't find any virus at all within the population."

That paucity of virus came as a surprise, given the sheer quantity of these thronging bats that could easily pass viruses among each other.

Then, in 2006, Plowright was out in Australia testing the bats again for Hendra virus. She'd even convinced a documentary team from National Geographic to come along to chronicle the dramatic swarms of bats in the sky. This time, however, she couldn't find any bats.

Where did the bats (and flowers) go?

"So we arrived and all of these hundreds of thousands of bats had disappeared," Plowright says. "There'd been a cyclone off the coast of Australia, and there was no food for the bats." The nectar sources they fed on were pretty much wiped out.

When Plowright and her crew finally did find a group of bats — fewer than 50 — they were emaciated, clearly starving from a lack of food. And when they sampled the bats' blood, it was teeming with Hendra virus. "That cued us that maybe nutritional stress is leading to infection and shedding of this virus in these bats," she says.

Plowright and her colleagues wanted further confirmation. So they looked back at 25 years' worth of data of another species of bat: black flying foxes in eastern Australia. And they found the same pattern: When the bats were well-fed on nectar, they had low levels of Hendra. But when they were hungry and emaciated, they were packed full of the virus. "They just don't have enough energy to maintain an immune response to keep these viruses in check," says Plowright.

She says that bats have historically been able to manage brief absences of food. But because of climate change and habitat loss in Australia, there just aren't as many of the flowering trees and plants that black flying foxes once relied on. So they're enduring longer periods of food deprivation, especially in winter. "In some parts of our study area," says Plowright, "96% of winter habitat has been cleared" for agricultural and urban development. "That is alarming."

"So the bats," she says, "can jump across the landscape, finding nectar in summer. But then in winter, there's nothing available." This means they have to look farther afield for food. "They fission into small populations and reside in urban and agricultural areas," Plowright says, "where they feed on species like fig trees that we plant in horse paddocks for shade or the weeds that grow across the landscape." And since the bats are loaded up with virus, often excreting it near horses, the stage is set for a Hendra spillover.

Expecting the worst .. but it didn't happen

The year 2020 was especially eye-opening. Horrific bushfires tore through the bats' winter habitat. The year prior saw hotter, drier El Niño conditions, which impacted the budding of the trees that produce the flowers and nectar that bats depend on. And food shortages led to mothers having less success raising their pups and higher overall mortality.

"Really everything told us that there was going to be a terrible cluster of spillover events of Hendra virus," Plowright. "And so we put out warnings, we asked people to vaccinate their horses." (A vaccine for horses became available in 2012 and is considered safe and effective.) In addition, she says, "We got our field teams on the go ready to respond to spillovers."

There was one spillover into a horse in May, and then... nothing. "So we were left scratching our heads," Plowright admits. "What's going on? What have we missed? This doesn't make sense."

It turns out there was this unexpectedly massive flowering of plants in the wintertime — mostly the blue gum tree — which drew in some 200,000 hungry bats. The reason for that flowering is unclear. But Plowright and her team looked again at the black flying fox data from the last quarter century.

"We were just stunned," she says. "Whenever there was winter flowering, there was never a spillover case." (That single spillover in May 2020 occurred before the flowering had started.)

As long as the bats had enough food, the virus didn't show up in people. Because these pulses of wintertime food are becoming less common due to the clearing of habitat, this suggests an elegant intervention.

"What we really need to be doing is planting those winter forests back and it's not a really difficult thing," says Plowright. "We're only talking about a handful of species that flower in winter. They're species that are habitat for koalas. There are huge landscape regeneration programs going on in Australia anyway, and so we just need to ensure that it's these winter flowering trees that are incorporated."

These findings from Plowright and her colleagues are published today (Nov. 16) in the journal Nature.

Gregory Gray, an infectious disease epidemiologist at the University of Texas Medical Branch who wasn't involved in the research, applauds the new study as compelling and "well thought out." He says it's a good example of how to use data to predict and mitigate spillovers, but he adds, "I guess the proof of the pudding will be: Does it work in the future?"

It's not just about Hendra virus

These findings extend beyond Hendra. They pertain to other bat-borne viruses, known and unknown. "If we can introduce solutions, particularly sustainable ecological solutions, that prevent the spillover of Hendra virus," says Alison Peel, a disease ecologist at Griffith University in Queensland and co-author on the paper, "then we would expect that we're also preventing the spillover of disease 'X' that we don't even know about yet."

Plowright says the same signs of spillover — of hungry bats breaking into small groups near urban and agricultural areas — have been observed elsewhere in Asia and Africa. She suspects it's happening all over; it's just not being documented.

"So the world is just being transformed at this alarming rate," she says, and animals are responding by changing their behavior to survive. Often that leads to virus shedding."

To give bat-borne viruses fewer chances of passing from animals into humans, Plowright has the following advice: Pay attention to bat habitat and plant the kind of trees that will keep bats well-fed — and healthy.

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