European Association of Zoo and Wildlife Veterinarians - Transmissible Diseases Handbook 2019 ELEPHANT ENDOTHELIOTROPIC HERPESVIRUS V14.05 OIE BALAI EU AHL VIRUS EEHV, Proboscivirus, Herpesviridae ZOONOSIS SUSCEPTIBLE PREVENTION TRANSMISSION CLINICAL SIGNS SEVERITY TREATMENT ANIMAL GROUPS AND CONTROL Elephants Unknown Asian elephants: High mortality in Any suspected Reduce stressful from silent mostly young case should be situations in the infection, fever, Asian elephants immediately elephant group swollen temporal treated with large Two lethal cases Early detection of glands, oral and a mounts of in young African viremia through vaginal vestibular rectal fluids elephants with a weekly CBC and mucosal lesions; high suspicion of In a few cases whole blood PCR to acute mortality other illness early treatment EEHV testing in young, swollen and/or altered with famciclovir, elephants at risk blue tongue, immune status ganciclovir or edema of head acyclovir has and front legs been considered African elephant: effective nodules in the Antibiotics to lungs, skin and prevent vestibulum enterotoxaemia vaginae, may be and septicemia occasionally fatal FACT SHEET COMPILED BY LAST UPDATE Willem Schaftenaar, DVM, Veterinary Advisor for the European Elephant TAG March 2016 FACT SHEET REVIEWED BY Gary S. Hayward, Johns Hopkins School Of Medicine, 1650 Orleans Street, Baltimore, MD 21287, United States of America Lauren L. Howard, DVM, Houston Zoo, 6200 Hermann Park Dr, Houston, TX 77030, United States of America DISEASE AGENT Elephant Endotheliotropic Herpesvirus, classified as a new Proboscivirus genus. Based on viral DNA-sequences, EEHV can be divided into eight major types: a) EEHV-1A and EEHV-1B: highly associated with death in Asian elephants worldwide. b) EEHV2: associated with death in 2 African elephants c) EEHV3: associated with transient disease in 1 African elephant d) EEHV4: associated with death in 2 Asian elephants e) EEHV5: associated with death in 1 Asian elephant f) EEHV6: associated with 1 lethal case in an African elephant g) EEHV2, EEHV3, EEHV6 and EEHV7 all found in saliva, lung and skin nodules of asymptomatic African elephants SUSCEPTIBLE ANIMAL GROUPS Asian elephants (Elephas maximus): fatal hemorrhagic disease is predominantly seen in animals between 1 and 8 years, less frequently up to 10 years. Minor lesions or unapparent infection in all ages. African elephants (Loxodonta africana): rarely fatal hemorrhagic disease in animals between 1-10 years; minor lesions may be found in otherwise healthy animals. Elephant Endotheliotropic Herpesvirus - Fact Sheet V14.05 European Association of Zoo and Wildlife Veterinarians - Transmissible Diseases Handbook 2019 ZOONOTIC POTENTIAL None known. DISTRIBUTION Captive Asian elephants in zoos of North America and Europe and Asia. More than 30 fatal outbreaks amongst captive and wild Asian elephants in Southeast Asia and India have been confirmed. Two cases of lethal EEHV2 and one of lethal EEHV6 in African elephants in North America and Asia respectively. TRANSMISSION Unknown, but plausibly by cell-cell contact through saliva and trunk secretions from asymptomatic shedders. The concept that EEHV in Asian elephants originates from African elephants has been completely abandoned based on phylogenetic evidences. INCUBATION PERIOD Unknown. CLINICAL SIGNS General information: the virus may be present in many, if not all, elephants in a latent state. Sometimes a correlation between stress and cases of EEHV has been suggested, but never proven. The disease presents as an acute hemorrhagic syndrome clinically similar to disseminated intravascular collapse and shock. The organ in which the virus persists is not known. Transient shedding of the virus (trunk, conjunctiva, oral and vaginal mucosa) has been demonstrated following periods of viremia. Asian elephants: present in a latent state in most, if not all, adult elephants. Recurrent mucosal lesions in the oral cavity and vestibulum vaginae have been reported, but most such lesions carry benign elephant gamma-herpesviruses instead. Gamma-herpesviruses are also commonly shed in saliva (five major types known in both Asian and African asymptomatic elephants). Young Asian elephants (1-8 years) are susceptible to fatal hemorrhagic EEHV-associated disease, which may be from a primary exposure to the virus. Clinical signs include lethargy, inappetence, lameness, altered sleep patterns, gastrointestinal signs, leukopenia, severe thrombocytopenia, cyanosis of the tongue and edema of the head and front legs. Death may occur within a few days or even hours of the observation of clinical illness, though subclinical viremia may persist for a week or more before clinical disease is apparent. A 42-year-old female Asian elephant died with signs of hemorrhagic EEHV-disease a few months after another adult female (that originated from a herd that suffered an EEHV case) was transferred to the zoo for the purpose of companionship. Reactivation of a silent EEHV should be considered in every severely diseased elephant; this means that the presence of EEHV can be expected in organs of any dead elephant that has been ill for a certain period. When EEHV has been detected and confirmed by PCR, a q-PCR should always be performed in order to measure the viral load and confirm a primary EEHV-associated fatality or a reactivation during an already existing disease process caused by another pathogen or process. African elephants: nodules in lungs and skin (EEHV2, EEHV3, EEHV6 and EEHV7 in both) and perhaps patches in the vestibulum vaginae (more likely gamma?). Occasional rare systemic disease with EEHV2, EEHV3 or EEHV6. Lower concerns about EEHV-involvement in acute disease processes compared to in Asian elephants, though more research is needed. PATHOLOGY AND POST MORTEM FINDINGS Cyanosis of the tongue, edema of the head and front legs. Inclusion bodies in endothelial cells of the heart, tongue, liver and other organs, severe hemorrhages due to blood vessel leakage. By electron microscopy, 80-92 nm diameter viral particles present within endothelial cells. DIAGNOSIS EEHV viremia can be detected via PCR and qPCR of whole blood (EDTA or heparin) and is the gold standard for detecting clinically significant EEHV-associated disease in at risk elephants. Ideally, this should be performed every 7 to 14 days in young elephants to detect viremia early. The viral load needs to be determined in order to evaluate the involvement of EEHV in the disease process (primary infection or reactivation). Mild leukopenia (monocytopenia) and thrombocytopenia may also support early EEHV viremia. PCR and q-PCR on swabs from mucosa (trunk wash, conjunctiva, genital tract) can demonstrate the presence of the EEHV virus and confirm shedding, which can happen in asymptomatic animals and is not associated with disease, but may be important from an epidemiologic or herd evaluation standpoint. [Caution: contamination from positive controls is a serious Elephant Endotheliotropic Herpesvirus - Fact Sheet V14.05 European Association of Zoo and Wildlife Veterinarians - Transmissible Diseases Handbook 2019 concern, but can be eliminated if novel strain found by DNA sequencing]. Associated diagnostic indicators: clotting of platelets and sharp decrease of platelets, monocytopenia. NB: hematocrit is usually within normal ranges. Post-mortem: endothelial inclusion bodies. PCR and q-PCR on tissue samples (heart, muscle/tongue, liver, spleen). In African elephants also PCR and qPCR on nodules of affected tissues. Serologic tests for EEHV1-antibodies: an antibody-ELISA (glycoprotein B based) has been developed at the Erasmus Medical Centre in Rotterdam. SAMPLES REQUIRED FOR LABORATORY ANALYSIS Daily swabs from mucosal lesions, immediately stored in virus buffer medium. EDTA or Heparin blood. Tissues: heart, liver, kidney, spleen, muscle, blood vessels, tongue, umbilical cord and larger blood vessels of the placenta (fresh or frozen; for retrospective studies formalin-fixated material has also been used thought it is not preferred). TREATMENT Mucosal lesions without other signs do not seem to pose a health risk to the animal and need no treatment (non- hemorrhagic ones are most likely gamma-herpesvirus related anyway). Contact animals may be at risk during this excretion phase and should be monitored carefully. Immediately after the onset of general clinical signs of unknown etiology, blood should be checked on the presence of EEHV (PCR and q-PCR) and while still waiting for the results, EEHV-treatment should be initiated immediately. Treatment consists of administration of large amounts of rectal fluids (water), and famciclovir which should be given either orally or rectally. In the latter case, the drug should be mixed with water and flushed gently into the rectum (arm-length from the anus) after very gently cleaning and flushing of the rectum. Dose of famciclovir: 15 mg/kg BW po or rectally TID. Period of treatment depends on presence of EEHV in blood. The anti-viral drug administration should be combined with antibiotics and supportive therapy against shock. In case of thrombocytopenia, monocytopenia, or ongoing disease, plasma transfusions should be given immediately (after minor cross matching between donor and recipient). Complete treatment protocols are available at http://eehvinfo.org/ PREVENTION Acute disease is likely predominantly from primary infection in naive animals. Stress in a donor herd mate may be a factor in triggering transmission leading to clinical disease in the susceptible