'Devastating' virus killed 2 Indianapolis Zoo elephants. Their deaths may save others.

Kalina and Nyah were special from the moment they were born. And that was largely because of how: The two young African elephants were born at the Indianapolis Zoo through artificial insemination. They were among the first in the world to be conceived through this method after more than a decade of unsuccessful efforts to breed the species in captivity.

Their birth was an outstanding achievement for science and animal conservation. That made their deaths last year — at 8 and 6 years old, respectively — especially painful.

In March of 2019, the Indianapolis Zoo lost the two young females during an outbreak of Elephant Endotheliotropic Herpesvirus, or EEHV, Hemorrhagic Disease — a disease that previously was thought to affect mainly Asian elephants. Their death brought new challenges to understand the disease, this time, in the African giants.

“The best way to honor our loss (of these elephants) is to prevent this disease and to share with others our story so that zoos can be prepared,” said Jill Sampson, elephant area manager at the Indianapolis Zoo.

World Elephant Day, celebrated on Aug. 12, is the chance to revisit the efforts of the Indianapolis Zoo and others over the last year to protect and preserve these elephants.

EEHV is a herpesvirus naturally found in both Asian and African elephants. Nearly all the seven known strains — or virus variants — can result in disease and death. But until now, scientists thought EEHV was more common in Asian elephants. However, the Indianapolis Zoo outbreak made evident that the African species may be just as vulnerable.

"It was just really thought to be almost an anomaly in African elephants and really not something you realistically worried about," said Jeff Proudfoot, senior veterinarian at the Indianapolis Zoo.

It also highlighted the importance of understanding and preparing for more possible cases among African elephants. The disease can strike without warning, there is no vaccine for it, and there is no way to prevent it.

“It’s a devastating disease. It's emotionally devastating for staff to lose a baby elephant that they are essentially raising with the help of the mother, of course, but as part of their family,” said Deborah Olson, executive director of the International Elephant Foundation and former director of conservation and science programs at the Indianapolis Zoo.  

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After the 2019 outbreak at the Indy zoo, researchers from across the nation decided it was time to come together to discuss EEHV in African elephants. So in February of 2020, veterinarians, scientists, elephant managers and keepers from all over gathered in the Indianapolis Zoo auditorium for the African Elephant EEHV Workshop. The purpose of the conference was to hear what others had been learning from EEHV in Asian elephants, in hopes of being able to use that knowledge for combating the disease in the African species.

Among those who attended the workshop in Indy was Paul Ling, an associate professor at Baylor College of Medicine in Texas. He first learned about the Indianapolis Zoo outbreak during the previous workshop in Houston in March last year. Back then, EEHV hemorrhagic disease in African elephants was thought to be rare.

“It was a bit of a surprise,” he said. “It had only been a handful of cases in African elephants.”

Ling’s research mostly focuses on the EEHV strains that affect Asian elephants. After the Indianapolis Zoo’s outbreak, however, he is now interested in understanding the ones affecting the African species.

Using blood samples taken from the ears of elephants at the Indianapolis Zoo, Ling and his group in Houston found antibodies for a protein specific to the EEHV virus coat. This showed that all elephants in the herd had had some type of herpes virus in their system at some point in their lives, explained Jeff Proudfoot, senior veterinarian at the Indianapolis Zoo.

Ling’s team continued working to identify the specific strains of EEHV the herd had been exposed to. Being a member of the herpesvirus family, EEHV shares many features with herpesviruses that commonly infect humans, said Ling. Once an elephant becomes infected, the virus can become latent but, for reasons that are still unknown, may later reactivate.

After testing, Ling's team found that the three surviving Indy elephants – Ivory, Zahara and Kedar – had antibodies for a protein specific to EEHV3. The elephants that died, Nyah and Kalina, did not.

The virus might infect an elephant and not make it sick: Adult elephants with an active EEHV infection may experience a mild disease with no or few symptoms. Ivory, Zahara, and Kedar, who survived the outbreak, had been infected by EEHV3 without anybody noticing. This allowed them to develop antibodies.   

Some young elephants, however, develop a fatal bleeding disease. 

Without the antibodies, this meant that these two young females, the Zoo’s youngest elephants when they died, were vulnerable to EEHV3, the strain responsible for the 2019 Indy outbreak.

“It’s (affecting) our young elephants, the future breeders. These are elephants that we've put in two or three years of work, even to get a baby on the ground," said Lauren Howard, associate director of veterinary services for the San Diego Zoo Safari Park. "And then another 10 to 12 years of care and training, and just right before they get to reproductive age, they get sick and die.”

“This is hitting our most important animals in our population when we look at a sustainability level,” added Howard, who also attended the conference in Indy in February of 2020.

But why would it be important to investigate a viral disease in elephants? Facing habitat fragmentation, ivory poaching, human-elephant conflict, and other emerging threats, zoos have become instrumental in preventing elephants from disappearing from the Earth. Researching and understanding the disease in zoos gives information to protect wild populations in their native range.

The virus was discovered in 1995 after Kumari, a 16-month-old Asian elephant, died at the Smithsonian’s National Zoo from unknown reasons. Veterinarians initially thought Kumari had been victim of a bacterial infection, but they needed to confirm. Laura Richman, then a veterinary pathology resident at the National Zoo, put some blood vessel-lining tissue under the electronic microscope and saw, for the first time, evidence of the new virus.

“It was a minute or two (of) putting it under the microscope when I saw it. And it led down that road of, it could be a viral infection and then (asking) what is it,” said Richman.

Those two minutes made her wonder how many more elephant deaths had been misidentified. She went back to the archives: paraffin blocks and glass slides with elephant tissue and confirmed that many of the elephant deaths attributed to intoxication or bacterial infection had been, in fact, victims of EEHV.

Back in 1999 when the International Elephant Foundation started funding EEHV studies, nobody really knew how important basic research would help understand the disease and, potentially, save elephants.

“I think we all knew it (EEHV) was going to be very significant, but it was so new, we just didn't know how significant it would be,” said Olsen.

After losing Nyah and Kalina, elephant trainers at the Indy Zoo became hyper-vigilant and realized Kedar, the only male of the herd, started showing slight symptoms. Blood samples taken from his ears revealed high levels of the EEHV HD virus. Those results prompted immediate treatment with an existing antiviral drug called famciclovir, which is used to treat some herpesvirus infections in humans. But there is a problem.

“We don’t know if it’s effective. The only way to know is to grow the virus in the lab. The evidence (of its effectiveness) is only anecdotal,” said Melissa Fayette, associate veterinarian at the Indianapolis Zoo.

“The antiviral might be in the blood, but if it doesn’t work, then what good is it?” echoed Howard in San Diego.

To test the drug’s effectiveness, scientists would first need to grow the virus in the lab and then apply famciclovir. But that’s much easier said than done, explains Richman, who was the first person to try.

“I think at that time everyone just thought I was inexperienced in trying to do this, but it turns out, nobody can grow this thing,” she said. “So there's something that's very unique about this virus.”

“Growing the virus would fasten the process of understanding,” Ling added. “(It is a) huge challenge not to be able to grow the virus.”

A vaccine would offer greater hope, the scientists said. As Ling and his colleagues are currently working on developing an EEHV vaccine for Asian elephants, they are hopeful their advances will help to develop one to protect African elephants.

“We think because of all the work that's been done in Asian elephants, it'll make things go a little quicker into figuring out how to develop a vaccine for the African elephants,” Proudfoot said.

A lot of progress has been made since EEHV was first discovered over two decades ago. The National Elephant Herpesvirus Laboratory, where blood samples of elephants from around 40 zoos across the country are analyzed, was set up.  

“When I started this way back, I was the only person. Many people were kind of chuckling that I was working on an elephant virus,” said Richman. “Now there are so many people, there's an international meeting every year working with focus groups, I never would have imagined that.”

However, scientists realize there is still a lot to be done. Ling’s group at Baylor, along with collaborators at Johns Hopkins University, are currently sequencing the complete genome of the major EEHV variants affecting African elephants. They are using preliminary results to develop tests that more specifically detect the virus.

In Indianapolis, Sampson is confident their experience will help protect elephants living in other zoos.

“Because of what happened with our cases, zoos and other facilities are now testing the African elephants,” she said. “I truly believe that because of what we have been through we are going to save lives.”

The International Elephant Foundation funds research on EEHV. Donations for the Foundation can be made here: elephantconservation.org/fundraising/donate/.

Lorena Villanueva-Almanza is the 2020 AAAS Mass Media Fellow at the Indianapolis Star. She earned her PhD from the University of California Riverside in 2019 where she studied the taxonomy and ecology of Washingtonia, a group of palms found in southern California and Baja California, Mexico. She’s on Twitter as @lorevial.

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