Kumari, a 16-month old Asian elephant calf at the National Zoo in Washington, D.C., was the first elephant to be diagnosed with EEHV-HD when she died suddenly in 1995. Thus began a 27-year journey of discovery, celebrated research milestones, paradigm shifts, and worldwide collaboration to better understand how to protect our elephants from the virus.
The work against this virus has brought together zoological institutions, circuses, conservation organizations, world class medical facilities, and universities, their experts sitting side by side in countless workshops, symposia, and meeting rooms, from Texas to Singapore, over the last 20 years. Our access to elephant samples combined with expertise in elephant husbandry, veterinary care, bench top laboratory work, and virologic methods, has led to great leaps in information and understanding of the virus. We’ve debunked many myths about EEHV, including the suggestion that it leapt from African elephants to Asian elephants (this is not true, the virus has evolved with both species of elephants for millions of years), and that it occurs only in elephants under human care (wild elephants in India and in South Africa have had EEHV detected in their blood, saliva, and organs). We’ve also taken what we’ve learned in caring for our elephants in North America, and shared our initial treatment protocols with colleagues in Asian and European EEHV working groups. These collaborators have worked with us to build on and improve techniques and to further advance research on detection, treatment, and epidemiology of EEHV.
Unfortunately, our work continues.
Since the end of 2020, EEHV has claimed the lives of five young Asian elephants at the ABQ BioPark in Albuquerque, N.M.; Rosamond Gifford Zoo in Syracuse, N.Y.; and the Columbus Zoo in Powell, Ohio; and a young African elephant at the Toledo Zoo in Toledo, Ohio. These young elephants were vitally important to the future sustainability of their respective elephant populations, and they were beloved by their zoo caretakers and the zoo-going public. While we have learned much about the genetics of the virus, how to detect it in an elephant, how to diagnose EEHV-HD early, before the elephant even appears sick, and how to support the elephant through illness, we have not yet found the breakthrough that ensures every young elephant that becomes ill from EEHV-HD survives it.
Many institutions that care for elephants are collaborating, and sharing staff, supplies, and resources when needed, and the survivors and the losses are celebrated and mourned by the entire elephant community. With new tools such as EEHV antibody measurement available, and the development of a vaccine on the horizon, there is much to be grateful for, and still work to be done.
Elephant endotheliotropic herpesvirus (EEHV) is a natural infection in elephants and has evolved with elephants for millions of years. Like many herpesviruses, it can live within its host without incident, and it can also cause acute often fatal hemorrhagic disease (EEHV-HD) in both Asian elephants (Elephas maximus) and African elephants (Loxodonta africana). EEHV is the leading cause of death in Asian elephants born in North America since 1980.
EEHV Hemorrhagic Disease (EEHV-HD) has a rapid progression and death can occur within hours after the first signs of illness are observed. The first clinical symptoms often include subtle changes in behavior, appetite, water consumption, activity or response to training and can be easily overlooked and attributed to other factors. The virus damages the endothelial cells lining the blood vessels which results in leaking of fluid and blood (edema and hemorrhage) in most organs. Hemorrhagic shock develops when blood loss leads to inadequate tissue oxygenation, and the elephant’s tongue appears blue (cyanotic).
A major breakthrough in EEHV research in 2010 determined that the virus can be detected in the blood by quantitative polymerase chain reaction (qPCR) up to ten days before the elephant shows signs of illness. Therefore, one important tool in our EEHV vigilance toolbox is to regularly monitor young elephants’ blood for presence of the virus and for changes in the complete blood cell count, or CBC. Decreases in platelets, and total white blood cell count, leukocytes and monocytes occur with early EEHV HD and are often seen on the CBC prior to other clinical signs.
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All adult elephants are latent carriers of EEHV, having survived exposure and an infection at some point in their lives. Healthy adult African and Asian elephants shed EEHV intermittently throughout their lives. EEHV species endemic to Asian elephants include EEHV1, EEHV4 and EEHV5 while African elephants shed EEHV2, EEHV3, EEHV6 and EEHV7. In Asian elephants most clinical disease and fatalities involve 1A and 1B whereas fatalities in African elephants have occurred with EEHV2, EEHV3, and EEHV6. The virus is found in trunk secretions, and studies are underway to determine to what extent the virus is shed through the saliva and feces.
Young elephants are most at risk, with EEHV-HD usually affecting Asian elephants between one and eight years of age and African elephants between one and 15 years of age. In just the last 18 months, due to very recent research advances, it is also finally possible to measure antibody levels to EEHV types and subtypes in young elephants and thereby determine if they are susceptible (naïve) to a particular EEHV. Research has shown that most newborn elephants are born with the same amount of antibodies to EEHV as their mother has, which is often very high. As maternal antibodies in the elephant calf decrease over time, some calves may not produce their own antibodies right away, and this leaves them vulnerable to developing often fatal EEHV-HD. We believe that early life exposure to the EEHV virus, as it is shed naturally by healthy adult elephants in the herd, is important to helping the young calf develop its own protective antibodies.
While the EEHV community has made tremendous strides in preparedness, diagnostics, and treatment of ill elephants, there is still much to be done. Managing an ill elephant through a case of EEHV hemorrhagic disease requires weeks of intensive, round the clock care by the elephant and veterinary teams.
Currently, antiviral treatment is still a hallmark of treating EEHV-HD. While we have pharmacokinetic studies showing elephants can absorb the antiviral famciclovir and achieve adequate drug levels in their circulation, we lack the science to show that famiciclovir actually inactivates EEHV. Despite 30 years of trying, EEHV scientists have been unable to culture the EEHV virus in the laboratory, which makes drug efficacy studies, as well as many other tests, impossible. Famiclovir, acyclovir, and ganciclovir have been used to treat EEHV-HD. Large amounts of famciclovir are required to treat an elephant; therefore, it is imperative that institutions maintain adequate amounts in stock. It is recommended that institutions maintain enough famciclovir to treat all at risk elephants for at least three days. Famciclovir used to be prohibitively expensive; now that the generic form is available, its cost should not deter any institution with elephants from purchasing it.
Supportive care is just as important (possibly more so) as antiviral therapy, and includes rectal fluids administered three-to-four times daily, frequent (often daily) intravenous administration of plasma and crystalloids, antibiotics, anti-inflammatories, opioids, and gastro-protectants.
In the past ten years, we have recognized the value of administering elephant plasma to elephants with EEHV-HD, and it has become a hallmark of the supportive care that helps an elephant survive EEHV-HD. Most often, administration of plasma transfusions requires standing sedation of the elephant to ensure good vein accessibility for the one to two-hour long procedure. Crossmatching, a procedure performed in a laboratory, can determine which elephants are safe donors for which elephants, to avoid transfusion reactions. Collection, processing, and proper storage of elephant plasma, in anticipation of an EEHV-HD event, is a key focus of many institutions caring for at-risk elephants. This requires special blood collection equipment, the laboratory equipment needed to centrifuge bags of whole blood, and reliable freezers that can store plasma long term. Recently, many institutions have been administering famciclovir orally to an elephant blood donor, and collecting and banking plasma one hour later, as a way to “immortalize” famciclovir before it expires, and to add antiviral activity to the plasma to be given to a sick elephant.
Groups in the U.S. and Europe are working on vaccines. A vaccine for Asian elephant EEHV1 has been developed and a clinical trial is underway. Work has started on a vaccine for the most lethal strain affecting African elephants as well.
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All elephant holding institutions should have a strong working knowledge of EEHV and a basic EEHV plan detailing how to collect and submit samples for EEHV qPCR testing, and how to treat a sick elephant. Any institutions that are allowing elephants to breed, and/or caring for elephants under 20 years of age should have a comprehensive EEHV protocol that includes vigilant observation of their animals and regular monitoring of at-risk animals for EEHV viremia via whole blood qPCR and CBCs. Institutions need to keep an adequate supply of anti-viral medication, frozen plasma, and blood transfusion supplies necessary to treat at risk individuals.
Elephants should be trained by one year of age for blood collection, trunk wash, physical examination, to receive oral and injectable medications, and administration of rectal fluids. Adult elephants should be trained for collection of plasma and whole blood. Having a plan for how to perform standing sedation of a young elephant is important to facilitate testing and treatment and is key to a successful outcome.
EEHV emergency response drills should be performed regularly, and the institutional EEHV protocol should be re-evaluated and updated every one to two years. The public relations department, zoo administrators, elephant leadership team, and veterinary team should develop a decision tree, an EEHV fact sheet, communication strategy, and logistical support structure for the benefit of all stakeholders. There will not be time for long meetings during an active case and having an efficient and effective response plan is critical to success.
By targeting young elephants within the herd, EEHV drastically reduces the future reproductive potential of the herd. At the Asian EEHV Strategy meetings in 2015 and 2016, more than 80 cases of EEHV-HD were identified among most Asian elephant range countries, with less than five elephants surviving and 12 deaths identified in free-ranging elephants in India. It is assumed free-ranging African elephants are also at risk and field studies are monitoring EEHV in these populations as well. Some countries lack diagnostic laboratories capable of testing for EEHV, but this need is being addressed by regional EEHV working groups and NGOs.
Yes, the North American EEHV Advisory Group is an excellent resource for information and assistance. Their mission is to disseminate knowledge of current best practices for prevention, diagnosis, and treatment of EEHV. The EEHV Advisory Group also provides private and public elephant-holding facilities with technical assistance and facilitates research by building international collaborations. The EEHV Advisory Group consists of individuals that focus on guiding the group’s mission, veterinary care, elephant management, research, pathology, public relations, education, and international liaisons. There are parallel regional working groups in Europe, Thailand, Asia, and Africa. These groups are an indispensable resource when faced with treating an elephant with EEHV. It is advised to sign up for access to the Professional Content on the website before experiencing an EEHV event to access the documents and planning resources there.
Photos Credit: © Dallas Zoo
The Article was produced by The North American EEHV Advisory Group.