“Shadow, Lightning, Calceti’n and Elusive Star as well as the others received the very best care money could buy,” Denise Bowden, a spokeswoman for the Chincoteague Volunteer Fire Company, which manages the herd, said Friday night on Facebook. “They just couldn’t fight this off.”

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Managers of the herd worry that warmer weather come spring will bring yet more infections and, potentially, a serious threat to the beloved ponies, one of the region’s iconic tourist draws and a feature of the Virginia coast for centuries.

“We’re not panicking, but we’ve never faced a situation like this before,” Bowden said as vets were still trying to save the four ponies the week before Christmas. “It’s been very, very trying.”

Most of the 150 or so horses roam loose in different parts of the refuge. But Bowden was standing next to a pen where several late-born ponies were spending their first winter with their mothers. Sheltering from the offshore breeze behind a line of bush, the gangly foals alternately dozed in the sun and nudged the mares for milk. A group of three adult horses grazed in an adjacent enclosure, newly arrived gifts from Chincoteague pony raisers wanting to replace some of the recently lost animals.

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In the middle of the compound is a long shed newly fitted with canvas sides. Inside, the four remaining infected animals were being seen regularly by two herd veterinarians. Before their deaths, about 20 volunteers from the fire company tended to their daily needs, which included removing and burning the stable muck.

The unexpected malady is pythiosis, an infection typically caused when a horse steps in water carrying a fungus-like organism known as Pythium insidiosum. Pathogens can enter small cuts or abrasions and, in some horses, create itchy, swelling lesions that will eventually become tumor-like growths. Untreated, the infection is invariably fatal.

The disease, sometimes known as swamp cancer, strikes mostly horses and dogs and has long been known in subtropical areas, including Florida. But ­cases are becoming more common in higher latitudes in recent years, with some reported as far north as Minnesota.

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“It’s an emerging disease,” said Richard Hansen, a research veterinarian in Oklahoma working on a vaccine and new treatments for pythiosis. “It seems to be moving north with the changing climate.”

There have been occasional unconfirmed cases of the disease among Chincoteague ponies over the years, according to Charles Cameron, the herd’s primary veterinarian for 29 years. But he’s seen nothing like the spate that began two years ago and spiked significantly this past autumn.

It was in late summer of 2016 when volunteers spotted a mare with small sores above her hoofs. Blood tests would confirm pythiosis and, caught early, it was successfully treated. But finding it at that initial stage may have been rare luck, as the ponies roam largely unmonitored over more than 4,000 acres. In 2017, two more infected animals were found with more advanced infections and, despite aggressive treatment, both died.

This past year, one was successfully treated in the spring, Cameron said. But then started a grisly run. In late August, volunteers spotted a 13-year-old mare, Lyra, with suspect lesions. Several other cases were diagnosed in the fall, prompting managers to set up an intensive treatment regimen that has included immunotherapy and, in some cases, cutting away infected tissue surgically. The group has spent more than $25,000 on treatments.

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“When you don’t catch it early, it’s just out of control,” Cameron said of the rapid growth of the tumor-like tissue. “It’s like a brain growing on their fetlock.”

At one point, hopes grew that at least some of the horses could be saved. But secondary infections set in and the pythiosis seemed to return in some cases. One pony died in October, another on Dec. 3. Two weeks later, Lyra was euthanized after she was no longer able to stand.

“It’s horrible,” Bowden said. “I’ve seen grown men bawl like babies when we have to put a horse down.”

It would be hard to overstate the cultural and economic role the horses have played here for centuries. They are long-feral descendants of domesticated livestock, and local legend has it that they first swam ashore as refugees from a foundering Spanish ship in the 1600s. Biologists, though, say they are more likely remnants of animals introduced by mainland settlers.

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Whatever the origin story, they have long been a defining feature of island life, cared for by folks, like Bowden, who grew up with them on Chincoteague and beloved by visitors from around the world, including many entranced by the 1947 children’s classic “Misty of Chincoteague.” With about 1.3 million visitors a year, the herd is a 150-horsepower economic engine that keeps the refuge near the top of Virginia’s most popular tourist destinations.

The geography of the ponies can be confusing. Chincoteague is an island of motels and houses. But the Chincoteague National Wildlife Refuge, where the ­horses spend most of their time grazing, is actually on Assateague, an undeveloped island just across a narrow saltwater channel. (The flip-flop comes from a tradition of naming such federal facilities after the nearest post office.)

The horses have a permit that lets them roam across the refuge in three fenced areas. Three times a year, they are rounded up and corralled for veterinary care. And each July, as tens of thousands look on, they are driven across the channel at low tide for an auction that keeps the herd’s numbers in line and raises money for the fire company.

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The fame of the herd has proved to be an asset as the local veterinarians reach out to experts for help in addressing the outbreak. Robert Glass, a Texas-based researcher, has been providing his new immunotherapy drugs free of charge.

“He read ‘Misty’ as a kid,” Cameron said.

And Hansen, who hopes to secure final government approval for his company’s pythiosis vaccine in 2019, is seeking permission to vaccinate the Chincoteague herd even sooner on an experimental basis, a prospect that Cameron hailed as their best chance to avoid a bigger epidemic.

An effective vaccine would protect the herd, but it wouldn’t clear the pathogen from the natural habitat, Hansen said, especially with more infected horses spreading it from pool to pool. Still, the keepers of the ponies want the refuge to take action, including clearing away old barbed wire that can be exposed by storms and increase the risk of cuts. The organism can’t penetrate healthy skin.

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Refuge officials said they were in contact with the herd managers and were exploring steps they could take. No other animals have been found with the infection, they said.

“There’s a lot we don’t know,” said Michael Dixon, the refuge’s visitor services manager. “But we’re partners, and we’ll do what partners need to do.”

He was walking on Assateague’s southern end, a patch of bristly pine trunks denuded by a recent pine beetle infestation. It’s not easy living for anything on an island that, in biological terms, ranks as an extreme habitat.

Not far away stood a group of the refuge’s most famous residents, casting long shadows in the winter sun. The stallion and three mares picked for greens amid the cold, dormant marsh grass, grazing their way through a season of uncertainty.

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Correction: An earlier version of this story mistakenly placed Michael Dixon at the north end of the wildlife refuge. It was the southern end.