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Clinical and Vaccine Immunology, July 2006, p. 722-732, Vol. 13, No. 7
1071-412X/06/$08.00+0     doi:10.1128/CVI.00133-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Tuberculosis in Elephants: Antibody Responses to Defined Antigens of Mycobacterium tuberculosis, Potential for Early Diagnosis, and Monitoring of Treatment

Konstantin P. Lyashchenko,1* Rena Greenwald,1 Javan Esfandiari,1 John H. Olsen,2 Ray Ball,2 Genevieve Dumonceaux,2 Freeland Dunker,3 Carol Buckley,4 Michael Richard,5 Suzan Murray,6 Janet B. Payeur,7 Peter Andersen,8 John M. Pollock,9 Susan Mikota,10 Michele Miller,11 Denise Sofranko,12 and W. Ray Waters13

Chembio Diagnostic Systems, Inc., Medford, New York,1 Busch Gardens Tampa Bay, Tampa, Florida,2 San Francisco Zoo, San Francisco, California,3 The Elephant Sanctuary, Hohenwald, Tennessee,4 Albuquerque Biological Park, Albuquerque, New Mexico,5 National Zoological Park, Washington, D.C.,6 United States Department of Agriculture, Animal and Plant Health Inspection Service, National Veterinary Services Laboratories, Ames, Iowa,7 Statens Serum Institut, Copenhagen, Denmark,8 Bacteriology Department, Veterinary Sciences Division, Stormont, Belfast, United Kingdom,9 Elephant Care International,10 Disney's Animal Programs, Lake Buena Vista, Florida,11 United States Department of Agriculture, Animal and Plant Health Inspection Service, Animal Care, Albuquerque, New Mexico,12 United States Department of Agriculture, National Animal Disease Center, Ames, Iowa,13

Received 5 April 2006/ Returned for modification 5 May 2006/ Accepted 11 May 2006

Tuberculosis (TB) in elephants is a re-emerging zoonotic disease caused primarily by Mycobacterium tuberculosis. Current diagnosis relies on trunk wash culture, the only officially recognized test, which has serious limitations. Innovative and efficient diagnostic methods are urgently needed. Rapid identification of infected animals is a crucial prerequisite for more effective control of TB, as early diagnosis allows timely initiation of chemotherapy. Serology has diagnostic potential, although key antigens have not been identified and optimal immunoassay formats are not established. To characterize the humoral responses in elephant TB, we tested 143 serum samples collected from 15 elephants over time. These included 48 samples from five culture-confirmed TB cases, of which four were in Asian elephants infected with M. tuberculosis and one was in an African elephant with Mycobacterium bovis. Multiantigen print immunoassay (MAPIA) employing a panel of 12 defined antigens was used to identify serologic correlates of active disease. ESAT-6 was the immunodominant antigen recognized in elephant TB. Serum immunoglobulin G antibodies to ESAT-6 and other proteins were detected up to 3.5 years prior to culture of M. tuberculosis from trunk washes. Antibody levels to certain antigens gradually decreased in response to antitubercular therapy, suggesting the possibility of treatment monitoring. In addition to MAPIA, serum samples were evaluated with a recently developed rapid test (RT) based on lateral flow technology (ElephantTB STAT-PAK). Similarly to MAPIA, infected elephants were identified using the RT up to 4 years prior to positive culture. These findings demonstrate the potential for TB surveillance and treatment monitoring using the RT and MAPIA, respectively.

* Corresponding author. Mailing address: Chembio Diagnostic Systems, Inc., 3661 Horseblock Road, Medford, NY 11763. Phone: (631) 924-1135. Fax: (631) 924-6033. E-mail: klyashchenko{at}chembio.com.

Clinical and Vaccine Immunology, July 2006, p. 722-732, Vol. 13, No. 7
1071-412X/06/$08.00+0     doi:10.1128/CVI.00133-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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