Abstract

A detailed account of the virologic and clinicopathologic features of a recently recognized fatal herpesviral disease of Asian (Elephas maximus) and African (Loxodonta africana) elephants has been described by our group.^5,6 We have determined that there are two closely related herpesviruses that infect elephants, one virus is lethal for Asian elephants and the other for African elephants. The predominant clinical signs for both species included lethargy, edematous swellings of the head and thoracic limbs, oral ulceration, cyanosis of the tongue and death in most elephants in 1–7 days. Pertinent laboratory findings in several of the clinically evaluated animals included lymphocytopenia and thrombocytopenia. Necropsy findings in the fatal cases included pericardial effusion and extensive petechial hemorrhages in the heart and throughout the peritoneal cavity, hepatomegaly, cyanosis of the tongue, and intestinal hemorrhage and ulceration. Histologically, there were extensive microhemorrhages and edema throughout the myocardium and a mild degree of myocarditis. Similar hemorrhagic lesions with inflammation were evident in the tongue, liver and large intestine. Lesions in these target organs were accompanied by amphophilic to basophilic, intranuclear viral inclusion bodies in capillary endothelial cells and transmission electron microscopy of the endothelial inclusion bodies revealed 80–92 nm-diameter viral capsids, consistent with herpesvirus morphology. Prior to the identification and description of this highly fatal herpesvirus disease in captive elephants,^4-6 there existed only several reports of herpesviruses occurring in skin papillomas¹ and pulmonary nodules² of African elephants by light and electron microscopy, but no references to herpesvirus in Asian elephants. At the time, these lesions with herpetic inclusion bodies in the African elephants were considered incidental or localized findings with no systemic illnesses associated with them, and no documentation of herpesvirus isolation. Polymerase chain reaction (PCR), followed by sequencing of DNA extracted from African elephant skin papillomas has identified an identical sequence in the terminase gene region as the virus lethal for Asian elephants.⁵ Similarly, a nearly identical viral DNA sequence was identified by PCR in biopsies of the lymphoid patches from the distal vaginal tract (vestibulum) of a wild African elephant which did not contain viral inclusion bodies histologically.^3,5

Morphologic evidence of herpesviruses in pulmonary nodules of wild African elephants has been documented.² These lung nodules are composed of lymphoid follicles which surround epithelial cells that contain intranuclear inclusion bodies and herpesvirus-like particles by electron microscopy. PCR followed by sequencing of DNA extracted from these lesions suggests that the herpesvirus present in African elephant lung nodules is the same virus that was lethal for the two African elephants with disseminated endotheliotropic disease.⁶ This may indicate that African elephants can latently harbor the two novel herpesviruses, one that can cause fatal endotheliotropic disease in Asian elephants and the other in African elephants. Three young Asian elephants recovered after a 3–4-wk course of therapy with the anti-herpesvirus drug famciclovir.⁷ One of these treated elephants showed a rapid abatement of clinical signs and return of hemogram values to normal, which coincided with a decrease in the concentration of herpesvirus in the blood as detected by temporal semi-quantitative PCR assays.⁶ Although we have documented an apparent carrier state for these herpesviruses in African elephants, the mode of transmission has not been proven. Assays to detect previous exposure and possible non-viremic carrier elephants are in the development stages.

Acknowledgments

Funded by NIH grant No. 1 K08 AI01526-01, the Smithsonian Scholarly Studies Program, the Kumari Elephant Conservation Fund and Friends of the National Zoo. The authors thank the following individuals and institutions for their contributions to our study: J. Cohen, National Institutes of Health; S. Feldman, Anmed/Biosafe Inc.; S. Mikota, The Audubon Institute; R. Mirkovic, Southwest Foundation for Biomedical Research; J. d'Offay and R. Eberle, Oklahoma State University; G. Letchworth, University of Wisconsin-Madison; K.E. Steele, B. Connolly and P. Jahrling, United States Army Medical Research Institute of Infectious Diseases; A. Ruebel, Zoo Zuerich; P. Ossent, University of Zuerich; F. Osorio, University of Nebraska, Lincoln; S. Kania and M. Kennedy, University of Tennessee, Knoxville; E. Dierenfeld, The New York Wildlife Conservation Society; J. Trupkiewicz, L. Munson and D. Taylor, University of California-Davis; D. Nichols, V. Bonshock, D. Fischer, A. Bratthauer, N. Spangler, K. Clark, J. Sutton, N. Pratt, M. Bush, J. Block and the elephant keeper staff, National Zoological Park; J. Jenkins and R.V. Ferris, Armed Forces Institute of Pathology; J. Gaskin, University of Florida; D. Olson, African elephant Species Survival Plan (SSP) coordinator; M. Keele, Asian elephant SSP coordinator; A. Schanberger, Houston Zoological Gardens; Marine World Africa-USA, Vallejo, CA; L. Bingaman-Lackey, AZA; N. Kriek, Univ. of Pretoria, S. Africa; R. Bengis, Kruger National Park, S. Africa; San Diego Zoo and Wild Animal Park; Center for Reproduction of Endangered Species (CRES); New York Wildlife Conservation Society; Lincoln Park Zoo; Dickerson Park Zoo; African Lion Safari; Tulsa Zoological Park; Fort Worth Zoo; Indianapolis Zoo; Dallas Zoo and the Oakland Zoo.

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