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February 18, 1999

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Deaths of Zoo Elephants Explained -- New Virus Identified

Researchers at Johns Hopkins in Baltimore and the National Zoo in Washington, D.C., have discovered the cause of death of nearly a dozen young North American zoo elephants -- fatal hemorrhaging from a previously unknown form of herpesvirus that apparently jumped from African elephants to the Asian species.

"This is very troubling because these are endangered species," said Gary Hayward, Ph.D., a Johns Hopkins scientist and co-author of a report published in the Feb. 19 Science. "And also because there may still be carrier African elephants in zoos."

Quick detection and treatment with antiviral drugs is life-saving, he added.

Asian elephants are bred more frequently in captivity than their African cousins, and a sufficient number of young elephants is necessary for bolstering the population, which is dwindling in the wild.

Of 34 Asian elephants born in zoos in the United States and Canada from 1983 to 1996, seven have died from the virus, and two more with incomplete records are suspected to have died from it. The virus appears to be latent in most African elephants, although two of seven African elephants born in North America over the past 15 years have also died from herpesvirus infection. Most of the infected elephants were young.

In their report, the scientists say that the elephant herpesvirus kills by infecting cells that line blood vessels in the heart, liver and other organs. Untreated, the virus soon causes internal bleeding and heart failure. The virus hits suddenly, killing in a few days.

The "index case," or first animal identified as having the virus, was a 16-month-old Asian elephant, Kumari -- the first elephant ever born at the National Zoo. When Kumari died in 1995, her keepers were baffled.

Soon after, Laura Richman, D.V.M., now at The Johns Hopkins School of Medicine, and Richard Montali, D.V.M., of the National Zoo, began investigating the case. When examining tissue samples from Kumari, they found tiny sacks of virus, called inclusion bodies. Using an electron microscope, the researchers saw that the viruses inside the inclusion bodies resembled herpesvirus. DNA analysis confirmed they were indeed dealing with a herpesvirus, although of a type not before identified.

Richman and her colleagues then went through old zoo records and found other elephant deaths in which the symptoms resembled those Kumari had suffered. After analyzing tissue samples from these previous deaths, the researchers confirmed the elephants had died from herpesvirus, leading them to watch out for other cases.

Other elephants were subsequently diagnosed with the virus, one in California in 1996, the second in Missouri in 1997, and the third last year in Florida. Upon hearing about the Missouri elephant, a calf named Chandra, veterinarians at the zoo prescribed the antiviral drug famciclovir. Chandra recovered in a few days. The Florida elephant also recovered after the same treatment.

"We were able to cure these elephants, which is promising. If caught early, the infection appears to be treatable," said Richman.

To see if the virus exists in the wild, the researchers worked with scientists in Zimbabwe and South Africa to collect blood and tissue samples from healthy African elephants. Again they found the virus, with DNA virtually identical to that found in the infected Asian elephants. This work confirmed that the virus exists in, but is nonlethal to, wild African elephants. It was also the piece of the puzzle that suggested how the zoo elephants became infected.

"It's likely that the virus is transmitted from the African to the Asian elephants in the zoos," said Richman. "That's the only way we can account for the same virus being present in both populations."

Hayward said a blood test is needed, to identify which elephants may be carrying the virus. He added that separating Asian and African elephants could prevent more deaths.

The research was supported by the National Institutes of Health, the Smithsonian Institution, the Kumari Elephant Conservation Fund, and Friends of the National Zoo.

Relevant Web sites:

Dr. Hayward's home page -- http://www.med.jhu.edu/bcmb/faculty/haywardg.html

National Zoo -- http://www.si.edu/organiza/museums/zoo/

Herpesviruses background -- http://www-micro.msb.le.ac.uk/335/Herpesviruses.html

Elephant Herpesvirus Q&A

Q: What is elephant herpesvirus?
A: It's a newly discovered virus that is killing zoo elephants. There appear to be two forms of the virus: one that kills Asian (or Indian) elephants and one that kills African elephants. The virus is distantly related to those that causes gential and oral herpes in people.

Q: Who discovered it?
Laura Richman, D.V.M., of The Johns Hopkins School of Medicine, Richard Montali, D.V.M., of the National Zoo in Washington, D.C., Gary Hayward, Ph.D., also from Hopkins, and Richard Garber, Ph.D., Pathogenesis Corp. in Seattle, did most of the work isolating and describing the virus and its effects. They report their findings in the Feb. 19 Science.

Q: How many elephants have died from the virus?
The researchers have confirmed 9 deaths, all zoo elephants in the United States and Canada. Two other zoo elephants with incomplete records also may have died from the virus. The first confirmed case is from 1983. Seven of the nine confirmed deaths were Asian elephants; the remaining two were African elephants. Most of the infected elephants were young, with four of the dead younger than two years old. Captive elephants outside North America, including a Swiss circus elephant, also may have died from the virus.

Q: How does the virus spread among elephants?
A: It appears that the virus jumps species. That is, African elephants seem to be carriers of the virus that kills Asian elephants, and vice versa. In the wild, the virus is latent in its respective species, causing no more harm than a benign wart. It's only when the virus crosses species -- from African into Asian elephants or vice versa -- that it becomes deadly. Because African and Asian elephants never have contact in the wild, the deadly effects of the virus were not seen until the two species began to mingle, like in zoos.

Q: How do the researchers know this?
Working with African scientists, they obtained skin and blood samples from wild elephants in South Africa and Zimbabwe. In these samples they found virus which had almost identical DNA to the herpesvirus found in the dead Asian elephants. This is strong evidence that the virus jumps from African to Asian elephants. The evidence that the virus jumps the other direction, from Asian to African elephants, is not as strong.

Q: How did the researchers discover the virus?
In 1995, the first elephant ever born at the National Zoo in Washington, D.C., Kumari, died mysteriously a few days after becoming ill. When Drs. Richman and Montali autopsied Kumari, who was just 16 months old, they found signs of virus. Later, DNA analysis showed that the virus was a previously unknown type of herpesvirus.

Q: How does elephant herpesvirus kill elephants?
Viruses usually target one type of cell -- for instance, the virus that causes human herpes infects skin cells. In the wild, the elephant herpesvirus also targets skin cells, but does not do any harm. However, when the virus crosses species, for some reason it attacks endothelial cells, which line the inside of blood vessels. No other known herpesvirus does this. Drs. Richman and Montali, who autopsied Kumari, found tiny sacks holding millions of copies of the herpesvirus inside capillaries in the heart and liver. This is where the virus does its damage -- it causes the capillaries to leak blood into the organs. Eventually the virus overruns so many capillaries that the internal bleeding overwhelms the heart, killing the elephant. The virus works quickly, killing in less than a week.

Q: Is the virus always fatal to elephants?
No. Two infected elephants, one at the Dickerson Park Zoo in Missouri, the second at the Ringling Brothers Conservation Facility in Florida, lived after veterinarians suspected a viral infection and treated them with a drug called famciclovir, which is used to treat human herpes. These two successes lend hope that elephant herpesvirus is curable when caught early.

Q: Can elephant herpesvirus infect people?
There is no evidence that the virus is dangerous to people.

Q: What are some other herpesviruses?
Scientists categorize the dozen or so identified herpesviruses into three groups: alpha, beta and gamma. The virus that causes chickenpox, varicella zoster virus, and those that cause human cold sores and genital lesions, called herpes simplex viruses, are in the alpha category. The elephant viruses appear to be most closely related to the beta group.

Q: Why is it important to understand the virus?
Asian elephants are endangered, and both Asian and African elephants are difficult to breed in captivity. In the past 15 years, only 34 Asian elephants and seven African elephants have been born in North America. As wild elephant populations decline, it is increasingly important that zoos make every effort to ensure the elephant's survival. This research could reduce the number of premature elephant calf deaths, bettering the chances of the survival of the species.

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