Elephant Endotheliotropic Herpesvirus (EEHV)May 30, 2017

Tales from the Wilder Side of Vet Med

Elephant Endotheliotropic Herpesvirus (EEHV)

Written by Rohit Malhotra, DVM, MBA

<strong>Fig. 1:</strong> EEHV was first identified in 1995 when Kumari Died suddenly at the National Zoological Park. <em>(Courtesy of Smithsonian National Zoological Park)</em>

Fig. 1: EEHV was first identified in 1995 when Kumari Died suddenly at the National Zoological Park. (Courtesy of Smithsonian National Zoological Park)

Introduction

The Asian elephant (Elephas maximus) population, which is estimated to be less than 50,000 internationally, is highly endangered. Therefore, every young Asian elephant calf born today provides greater hope for the species survival in captivity and in the wild. Unfortunately, a particularly virulent species of herpesvirus, discovered in 1995, accounts for large number of deaths in young Asian elephants (1-8 years of age). Elephant endotheliotropic herpesvirus (EEHV) is characterized by generalized hemorrhages systemically resulting in death within 24 to 48 hours of clinical onset with a mortality rate of 85 percent. Phylogenetically there are six strains that have been identified as EEHV1 to EEHV6 that occur only in elephantid hosts. EEHV1 is the most commonly isolated strain from the 60 known EEHV cases across North America and Europe within the past 10 years, and appears to be the most pathogenic.

Clinical Signs

Onset of initial signs are sudden but non-specific. These include lethargy, colic, diarrhea, constipation, lameness and anorexia. As the disease progresses, signs associated with blood loss and shock appear including tachycardia and tachypnea. Late stage signs include cyanosis of the tongue and cranial and extremity edema. Laryngeal ulcers have also been reported in the later stages for some calves. During the final stages, calves illustrate neurologic signs, including unresponsiveness to commands, possibly due to cerebral edema, and/or become recumbent.

Click on any of the images below to enlarge

<strong>Fig. 2: </strong>View of the tongue of an Asian elephant calf in the early stages of EEHV disease. Note the minor bruising on the right side of the tongue. <em>(Courtesy of Chiang Mai University).</em>

Fig. 2: View of the tongue of an Asian elephant calf in the early stages of EEHV disease. Note the minor bruising on the right side of the tongue. (Courtesy of Chiang Mai University).

Advanced EEHV in Asian Elephant

Fig 3: View of the tongue in the very advanced stages of the EEHV process. Note the marked cyanosis, caused by reduced circulating volume, reduced cardiac output, and progressive pulmonary edema. (Courtesy of Chiang Mai University).

severe edema around eye - Asian elephant

Fig. 4: Severe edema around the eye in an Asian elephant calf in the advanced stages of EEHV infection. (Courtesy of Chiang Mai University).

 

 

 

recumbent Asian elephant calf

Fig. 5: An Asian elephant calf in the late stages of EEHV infection with generalized edema of the head and neck, particularly noticeable is the swollen mandibular area. Some calves become recumbent, as shown above. Other calves can walk around until they literally drop dead. (Courtesy of Chiang Mai University).

 

 


Differential Diagnosis

Disease causing sudden onset and rapid death in Asian elephants include:

  1. Encephalomyocarditis (EMCV)
  2. Clostridial enterotoxemia
  3. Colibacillosis (E.coli)
  4. Pasteurellosis
  5. Salmonellosis
  6. Toxicosis (sodium fluroacetate)
  7. Hypovitaminosis E

Ante-mortem Diagnosis

Currently the assays used to diagnose EEHV are conventional polymerase chain reaction (cPCR) and quantitative PCR (qPCR). Clinical pathology findings include lymphopenia, thrombocytopenia, anemia, and dehydration. These blood cell changes may precede the appearance of clinical signs. The presence of lethargy, anorexia, colic, edema, and cyanosis of the tongue, provides further suspicion of EEHV illness.

Post-mortem Diagnosis

Unfortunately, in most cases, diagnosis is confirmed at necropsy. Gross lesions include pericardial effusion with petechial to ecchmotic hemorrhages on the heart surfaces. Petechiae is diffusely scattered within all the viscera and parietal peritoneal serous membranes. Hemorrhages can be present in the abdominal cavity, meninges, and brain. The tongue is usually cyanotic. Hepatomegaly is generally present. Ulcers may be observed in the oral and laryngeal cavities and intestines.

Histopathologic findings include vasculitis and thrombosis, often most severe in heart, kidneys, and liver. Interstitial edema and some hepatocellular degeneration is observed. Basophilic intranuclear inclusion bodies in capillary or sinusoidal endothelial cells are characteristic of EEHV but can be difficult to find in affected organs.

Fig. 6: Hydropericardium of an EEHV affected Asian Elephant calf.  (Courtesy of Chiang Mai University).

Fig. 6: Hydropericardium of an EEHV affected Asian Elephant calf. (Courtesy of Chiang Mai University).

Fig. 7: Diffusely scattered ecchymoses and petechiae involving the epi-, endo- and myocardium heart surfaces of an EEHV affected Asian Elephant calf. (Courtesy of Chiang Mai University).

Fig. 7: Diffusely scattered ecchymoses and petechiae involving the epi-, endo- and myocardium heart surfaces of an EEHV affected Asian Elephant calf. (Courtesy of Chiang Mai University).

 

 

 

 

 

 

 

 

 

 

 

 

Fig. 8: On opening of the pericardium the heart is often hemorrhagic.  (Courtesy of Chiang Mai University).

Fig. 8: On opening of the pericardium the heart is often hemorrhagic. (Courtesy of Chiang Mai University).

Fig 6: In most cases, several liters of hemorrhagic pericardial fluid are removed post-mortem.  (Courtesy of Chiang Mai University).

Fig 9: In most cases, several liters of hemorrhagic pericardial effusion are removed post-mortem. This fluid was drawn from the heart in fig. 8. (Courtesy of Chiang Mai University).

 

 

 

 

 

 

 

 

 

 

 

Fig. 10: Viral inclusion body (black line) within capillary endothelial cells in the heart are a hallmark of herpesvirus infection. (Courtesy of Smithsonian National Zoological Park).

Fig. 10: Viral inclusion body (black line) within capillary endothelial cells in the heart are a hallmark of herpesvirus infection. (Courtesy of Smithsonian National Zoological Park).

Fig. 11: Intracranial hemorrhages and edema in an EEHV infected Asian elephant calf. (Courtesy of Chiang Mai University).

Fig. 11: Intracranial hemorrhages and edema in an EEHV infected Asian elephant calf. (Courtesy of Chiang Mai University).

 

 


Prognosis

The prognosis for EEHV is poor. The disease has an 85 percent mortality rate, which is exceptionally high and on par with Ebola virus. However it is clear that the survival rate increases with early clinical observation and aggressive treatment. The survival rate is low for several reasons. First the virus is extremely virulent and disease progresses rapidly. Laboratory diagnosis of the disease can take more than 24 hours, yet the disease can cause death within 24 hours. Thus treatment must begin before EEHV is confirmed. In addition, treatment requires aggressive, around-the-clock care, necessitating trained animals, experienced veterinarians, and access to testing and treatment supplies.

Treatment

The first step of treatment is rectal administration of three to four boluses of lukewarm tap water at a dose of 10 – 20 ml/kg. Reassess vital signs and attitude and, if needed, continue IV colloids at the equine maintenance rates of 40 ml/kg/day. This can stop early signs of shock by drawing back extravascular fluid into the vascular compartment. Even before diagnosis is confirmed by PCR, starting a two-week course of famciclovir administered 16 mg/kg TID per rectum on Day 1 and then 12 mg/kg TID thereafter is beneficial.

Other supportive treatments include antibiotics and anti-inflammatory drugs to counter secondary infection and reduce or prevent further pathology.

Diuretics like furosemide or mannitol can be useful for the management of peripheral and cerebral edema. Supplemental oxygen therapy should be administered to all patients with clinical signs.

Plasma therapy might help intravascular clotting, especially since thrombocytopenia is present in most EEHV diseased calves. Plasma transfusion may cause an allergic reaction in the calf and it is advisable to check the cross-match. If plasma is not available, colloids should be used.

Currently there is no vaccine available for EEHV.

Prevention

It is generally accepted that all elephants are infected with EEHV hence keeping EEHV out of the herd is not possible. Herpesvirus outbreaks are generally related to a decrease in immunity so avoiding stress in elephants is an important preventative measure. This would include careful planning of elephant moves and introductions, especially during breeding and weaning while other calves are present. It is also important to separate African elephants and Asian elephants, particularly young Asian elephants, to avoid exposure risks. Confirm that elephant breeding facilities have a treatment regime in place for any possible EEHV cases.

Daily management of the herd by elephant staff is the most important preventative measure for EEHV disease. They should do daily oral checks of the tongue and mouth and observe any minor changes in color. They should report any minor changes in behavior and appetite. Daily oral temperatures should be taken as part of EEHV management because it is suspected that primary viremia could cause an increase in core body temperature. Veterinarians should obtain normal hematology and chemistry values from calves as early as blood sampling is possible and compare any values to these base line values. It is not recommended to use published reference ranges because changes can be very subtle.

Where to go to Learn More

If you wish to learn more about EEHV, please visit www.EEHVinfo.org. It is a scientific and evidence-based resource maintained by researchers, veterinarians, and elephant managers who are studying, treating, and caring for elephants with EEHV. Today the immediate focus of EEHV working groups worldwide is to increase education among elephant care takers (keepers, veterinarians, government officials), develop standard operating procedures for managing EEHV cases, and closely collaborate internationally to advance the understanding of EEVH.

About the Author

Rohit Malhotra, DVM, MBA

Dr. Rohit Malhotra received a BS in Leadership Management and a BA in Biology from Boston College in 2007. Prior to graduate school, he developed his management skills at several health care organizations in New England, including Harvard Medical School, Brigham and Women’s Hospital, and Partners HealthCare. He is a graduate of Colorado State University’s DVM / MBA dual-degree program, and joined Ethos as the first Veterinary Health Care Management Fellow in 2016.

As a Fellow, Dr. Malhotra was involved in developing a Lean Culture by utilizing and teaching process improvement strategies to enhance clinical efficiency. Currently Dr. Malhotra is managing the implementation of a new hospital information system across all the 14 hospitals of Ethos Veterinary Health.  This transition to a shared hospital information system will improve data collection, collaboration, efficiency, and quality of care for patients and clients across the Ethos network.

Dr. Malhotra also has a background in large animal medicine with a passion to improve elephant health care internationally.

Article Notes

References & Additional Reading:

References

Molenaar, F. (2016, Jul. 8 – 17). Elephant Endotheliotropic Herpesvirus: Latest Research and Current Protocols. Proceedings from Asian Elephant Health, Reproduction, and Breeding Management Conference. Chiang Mai, Thailand.

Luz, S. and Howard, L. (2015, Nov. 5 – 7) Elephant Endotheliotropic Herpesvirus (EEHV) in Asia. In: Recommendations from the 1st Asian EEHV Strategy Meeting.Singapore.

Richman, LK. et al. (2012). Elephant Herpesviruses. In: Fowler ME, Miller RE, editors. Zoo and Wild Animal Medicine: Current Therapy, 7th ed. p. 496 – 502. St. Louis, MO: Elsevier.

Wiedner, E. et al. (2012). Treatment of Elephant Endotheliotropic Herpesvirus. In: Fowler ME, Miller RE, editors. Zoo and Wild Animal Medicine: Current Therapy, 7th ed. p. 537 – 543. St. Louis, MO: Elsevier.

Photo credits:

Chiang Mai University, Thailand

Smithsonian National Zoological Park

 

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