© 2003-17 Susan K. Mikota DVM and Donald C. Plumb, Pharm.D. Published by
Elephant Care International
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Note: Detailed guidelines for the treatment of tuberculosis in elephants have been developed in the U.S.A. by the National Tuberculosis Working Group for Zoo and Wildlife Species. The drugs and dosages recommended are based on human treatment protocols and information obtained from pharmacokinetic studies in elephants (unpublished data). The reader is advised to consult the current Guidelines available at the following websites:
a) Pyrazinamide 30 mg/kg administered orally or rectally (Natl. TB Working Group, 2003).
b) Adverse effects: In one elephant under treatment for tuberculosis, a low grade anemia was observed when INH and pyrazinamide were administered rectally 4 times weekly. The anemia resolved when the INH dose was decreased from 3.75 to 2.5 mg/kg and the PZA dose was decreased from 35 to 25 mg/kg (Mikota et.al. 2001). Author’s (Mikota) note: It is likely that the anemia was caused by the INH rather than by pyrazinamide.
c) 30 mg/kg PO or by rectal administration as a starting dose based on PK data; monitor blood levels and adjust dose as needed (Zhu, 2005).
a) The National Tuberculosis Working Group for Zoo and Wildlife Species. 2003. Guidelines for the Control of Tuberculosis in Elephants. Internet links above.
b) Mikota,S.K., Peddie,L., Peddie,J., Isaza,R., Dunker,F., West,G., Lindsay,W., Larsen,R.S., Salman,M.D., Chatterjee,D., Payeur,J., Whipple,D., Thoen,C., Davis,D.S., Sedgwick,C., Montali,R.J., Ziccardi,M., and Maslow,J. 2001. Epidemiology and diagnosis of Mycobacterium tuberculosis in captive Asian elephants (Elephas maximus). Journal of Zoo and Wildlife Medicine 32:(1):1-16 Abstract: The deaths of two Asian elephants (Elephas maximus) in August 1996 led the United States Department of Agriculture to require the testing and treatment of elephants for tuberculosis. From August 1996 to September 1999, Mycobacterium tuberculosis infection was confirmed by culture in 12 of 118 elephants in six herds. Eight diagnoses were made antemortem on the basis of isolation of M. tuberculosis by culture of trunk wash samples; the remainder (including the initial two) were diagnosed postmortem. We present the case histories, epidemiologic characteristics, diagnostic test results and therapeutic plans from these six herds. The intradermal tuberculin test, enzyme-linked immunosorbent assay serology, the blood tuberculosis test and nucleic acid amplification and culture are compared as methods to diagnose M. tuberculosis infection in elephants.
c) Zhu, M, Maslow, J.N., Mikota, S.K., Isaza, R., Dunker, F., Riddle, H. and Peloquin CA. 2005. Population pharmacokinetics of pyrazinamide in elephants. J Vet Pharmacol Ther. 28(5):403-9.
This study was undertaken to characterize the population pharmacokinetics (PK), therapeutic dose, and preferred route of administration for pyrazinamide (PZA) in elephants. Twenty-three African (Loxodonta africana) and Asian (Elephas maximus) elephants infected with or in contact with others culture positive for Mycobacterium tuberculosis were dosed under treatment conditions. PZA was dosed daily at 20-30 mg/kg via oral (fasting or nonfasting state) or rectal (enema or suppository) administration. Blood samples were collected 0-24 h postdose. Population PK was estimated using nonlinear mixed effect modeling. Drug absorption was rapid with T(max) at or before 2 h regardless of the method of drug administration. C(max) at a mean dose of 25.6 (+/-4.6) mg/kg was 19.6 (+/-9.5 microg/mL) for PZA given orally under fasting conditions. Under nonfasting conditions at a mean dose of 26.1 +/- 4.2 mg/kg, C(max) was 25% (4.87 +/- 4.89 microg/mL) and area under concentration curve (AUC) was 30% of the values observed under fasting conditions. Mean rectal dose of 32.6 +/- 15.2 mg/kg yielded C(max) of 12.3 +/- 6.3 microg/mL, but comparable AUC to PZA administered orally while fasting. Both oral and rectal administration of PZA appeared to be acceptable and oral dosing is preferred because of the higher C(max) and lower inter-subject variability. A starting dose of 30 mg/kg is recommended with drug monitoring between 1 and 2 h postdose. Higher doses may be required if the achieved C(max) values are below the recommended 20-50 microg/mL range.
Mikota,S.K., Larsen,R.S., and Montali,R.J. 2000. Tuberculosis in Elephants in North America. Zoo Biology 19:393-403 Abstract: Within the past 4 years, TB has emerged as a disease of concern in elephants. The population of elephants in North America is declining (Weise,1997), and transmissible diseases such as TB may exacerbate this trend. Guidelines for all elephants for TB, were instituted in 1997 (USDA, 1997, 2000). Between August 1996 and May 2000, Mycobacterium tuberculosis was isolated form 18 of 539 elephants in North America, indicating an estimated prevalence of 3.3%. Isolation of the TB organism by culture is the currently recommended test to establish a diagnosis of TB; however, culture requires 8 weeks. Further research is essential to validate other diagnostic tests and treatment protocols.