Submitted to: Clinical and Vaccine Immunology
Publication Type: Peer reviewed journal
Publication Acceptance Date: 5/11/2006
Publication Date: 7/1/2006
Citation: Lyashchenko, K.P., Greenwald, R., Esfandiari, J., Olsen, J., Ball, R., Dumonceaux, G., Dunker, F., Buckley, C., Richards, M., Waters, W.R. 2006. Tuberculosis in Elephants: Antibody Responses to Defined Antigens of Mycobacterium tuberculosis, Potential for Early Diagnosis, and Monitoring of Treatment. Clinical and Vaccine Immunology. 13(7):722-732. Interpretive Summary: Tuberculosis is common in elephants in zoos, circuses, and wildlife parks within the United States. This infection represents a serious risk to elephant handlers; exhibit visitors, and other animals. At present, the only method to diagnose the infection is by culture of trunk wash samples. This method is exceedingly insensitive; thus, many infected elephants are not detected until very late in the course of disease. In the present study, it was determined that infected elephants produce antibodies to the bacterium and these antibodies are detectable by simple laboratory methods. Using this method of diagnosis, tuberculosis infection was diagnosed up to 4 years prior to the standard method of tuberculosis diagnosis of elephants (i.e., culture). Furthermore, it was determined that evaluation of antibody responses was a reliable method to evaluate the effectiveness of therapy to cure the disease. These findings will be useful for developing new strategies for surveillance of tuberculosis in elephants.
Technical Abstract: Tuberculosis (TB) in elephants is an important re-emerging zoonotic disease caused by Mycobacterium tuberculosis or M. bovis. Current diagnosis relies on trunk wash culture, the only official test, which has serious limitations. Therefore, innovative and efficient methods are urgently needed. Rapid detection of diseased animals is a crucial prerequisite for more effective control of TB, as early diagnosis allows timely initiation of antitubercular chemotherapy. Serology has diagnostic potential particularly for practical reasons, although key antigens are not identified and optimal immunoassay formats are not established. To characterize the humoral responses in elephant TB, we tested 140 serum samples collected from 15 elephants over time. These included 45 samples from 5 culture-confirmed TB cases, of which 4 Asian elephants were infected with M. tuberculosis and one African elephant with M. 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 by serum IgG during elephant TB. Antibodies to ESAT-6 and other antigens were detected up to 4 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. Similarly to MAPIA, infected elephants were detected using the RT up to 4 years prior to culture. These findings demonstrate the potential for TB surveillance and treatment monitoring using RT and MAPIA respectively.