International Fact Sheet
Susan Mikota DVM
Mycobacterium tuberculosis (most cases); humans are natural
M. bovis; (cattle are natural reservoir
atypical mycobacteria (non-tuberculous) (1 case)
Asian and African elephants susceptible
chronic, progressive, debilitating disease
aerosol transmission assumed
transmission from human to elephant or elephant to elephant
diagnosed in captive elephants in the U.S. and Europe
yet found in free-ranging elephants
M.tb has been isolated from feces (coughed and swallowed)
signs in elephants
of organism by culture
intermittent shedding so need 3 samples / test
serological tests promising
major organ disease
Zoonotic potential conversion
on PPD (skin test)
case of active TB documented (same strain as elephant)
appropriate precautions (use personal protective equipment)
for general information about TB
1. Todarís On-line
Textbook of Bacteriology:
4. Supercourse TB
6. American Thoracic
* Guidelines for the Control of Tuberculosis in Elephants:
Available on the Internet at the following sites:
(available to the public)
(available to AAZV members by password)
www.elephantcare.org/protoman.htm (available to the public)
References with Abstracts June 2005
Elephant Care International Bibliographic Database (www.elephantcare.org)
1. Lewerin,S.S., Olsson,S.L., Eld,K.,
Roken,B., Ghebremichael,S., Koivula,T., Kallenius,G., and Bolske,G. 2005.
Outbreak of Mycobacterium tuberculosis infection among captive Asian
elephants in a Swedish zoo. Vet Rec. 156(6):171-175.
Abstract: Between 2001 and 2003, there was an outbreak of tuberculosis in
a Swedish zoo which involved elephants, giraffes, rhinoceroses and
buffaloes. Cultures of trunk lavages were used to detect infected
elephants, tuberculin testing was used in the giraffes and buffaloes, and
tracheal lavage and tuberculin testing were used in the rhinoceroses. The
bacteria isolated were investigated by spoligotyping and restriction
fragment length polymorphism. Five elephants and one giraffe were found to
have been infected by four different strains of Mycobacterium
tuberculosis. National Veterinary Institute, SE-751 89 Uppsala, Sweden.
2. Maslow,J.N., Mikota,S.K., Zhu,M.,
Riddle,H., and Peloquin,CA. 2005. Pharmacokinetics of ethambutol (EMB) in
elephants. J Vet Pharmacol Ther. 28:321-323.
3. Maslow,J.N., Mikota,S.K., Zhu,M.,
Isaza,R., Peddie,L.R., Dunker,F., Peddie,J., Riddle,H., and Peloquin,CA.
2005. Population pharmacokinetics of isoniazid in the treatment of
Mycobacterium tuberculosis among Asian and African elephants (Elephas
maximus and Loxodonta
africana). J Vet Pharmacol Ther. 28(1):1-7.
Abstract: We recently described the clinical presentation and treatment of
18 elephants from six herds infected with TB. Treatment protocols and
methods varied between
herds to include both oral and rectal dosing using multiple drug doses and
formulations. In this paper we present information regarding the
pharmacokinetics (PK) of isoniazid (INH) in elephants and provide
suggestions regarding initial treatment regimens. Forty-one elephants
received INH daily by either oral or rectal administration with different
formulations. Population PK analysis was performed using Non-linear Mixed
Effect Modeling (NONMEM). Results of oral administration indicated that
compared with premixed INH solution, the drug exposure was highest with a
suspension prepared freshly with INH powder. When INH was concomitantly
given as an admixture over food, Tmax was delayed and variability in drug
absorption was significantly increased. Compared with oral administration,
similar drug exposures were found when INH was dosed rectally. The data
generated suggest that a starting dose of 7.5 mg/kg of INH is appropriate
for initial TB treatment in elephants when premixed solution is
administered directly into the oropharynx or rectal vault and 4 mg/kg are
when INH is administered following immediate suspension from powdered
form. Section of Infectious Diseases, VA Medical Center, Division of
Infectious Diseases, University of Pennsylvania, Philadelphia, PA, USA.
4. Pandey,R. and Khuller,G.K. 2005.
Antitubercular inhaled therapy: opportunities, progress and challenges.
Journal of Antimicrobial Therapy 55:430-435.
Zhu,M., Maslow,J.N., Mikota,S.K., Isaza,R., Dunker,F., and Peloquin,C.A.
2005. Population pharmacokinetics of pyrazinamide in elephants. Journal of
Veterinary Pharmacology and Therapeutics. Accepted for publication Dec
2004. In press.
6. Guidelines for the control of
tuberculosis in elephants.
7. Chakraborty,A. 2003. Diseases of
elephants (Elephas maximus) in India-A Review. Indian Wildlife Year
8. Michel,A.L., Venter,L.,
Espie,I.W., and Coetzee,M.L. 2003. Mycobacterium tuberculosis
infections in eight species at the National Zoological Gardens of South
Africa, 1991-2001. Journal of Zoo and Wildlife Medicine 34(4):364-370.
Abstract: Between 1991 and 2001 a total of 12 cases of Mycobacterium
tuberculosis infection in eight different species were recorded in the
National Zoological Gardens of South Africa in Pretoria (Tshwane). The
genetic relatedness between seven of the M. tuberculosis isolates
was determined by IS6110 restriction fragment length polymorphism
analysis. For the majority of the isolates that were analyzed, a high
degree of polymorphism suggested different sources of infection. Evidence
of M. tuberculosis transmission between animals is reported in two
chimpanzees (Pan troglodytes) housed together, from which samples
were collected for analysis 29 mo apart.
9. Pavlik,I., Ayele,W.Y., Parmova,I.,
Melicharek,I., Hanzlikova,M., Svejnochova,M., and Kormendy,B. 2003.
Mycobacterium tuberculosis in animal and human populations in six Central
European countries during 1990-1999. Veterinarni Medicina 48(4):83-89.
Abstract: Results of Mycobacterium tuberculosis detection in animals from
six Central European countries (Croatia, the Czech Republic, Hungary,
Poland, Slovakia and Slovenia) spreading over 610402 km2 with a population
of 11.8 million heads of cattle were analysed. In the monitoring period
between 1990 and 1999, M. tuberculosis from animals was isolated only in
two countries (Poland and Slovak Republic) from 16 animals with
tuberculous lesions. These comprise 9 cattle (Bos taurus), 4 domestic pigs
(Sus scrofa f. domestica) and three wild animals, an African elephant (Loxodonta
africana), agouti (Dasyprocta aguti) and terrestrial tapir (Tapirus
terrestris) from a zoological garden Gdansk in Poland. A steady decrease
in the incidence of tuberculosis in humans was recorded during the
monitoring period in all countries. The human population of the study
countries was 68.03 million. In the period monitored, infection caused by
M. tuberculosis was identified in a total of 241040 patients with a
decreasing incidence of tuberculosis found in all countries. The lowest
relative bacteriologically confirmed disease was found in the Czech
Republic, Slovak Republic and Slovenia. Given the low number of infected
domestic and wild animals, the epidemiological and epizootiological
situation may be considered auspicious.
10. Rahman,T., 2003. Infectious and
non-infectious disease of elephants. In Das,D. (Editor). Healthcare,
Breeding and Management of Asian Elephants.New Delhi Project Elephant.
Govt. of India, pp. 108-118.
11. Ziccardi,M., Wong,H.N., Tell,L.A.,
Fritcher,D., Blanchard,J., Kilbourn,A., and Godfrey,H.P. 2003. Further
optimization and validation of the antigen 85 immunoassay for diagnosing
mycobacteriosis in wildlife. Proc Amer Assoc Zoo Vet, pp. 219-220.
Abstract: Mycobacteriosis caused by Mycobacterium bovis, M.
tuberculosis and M. avium has been a well-documented health
problem for zoological collections as long ago as the late 19th
century. Prevalence estimation in these captive wildlife populations,
however, has been hampered by diagnostic test methods that are oftentimes
difficult or impossible to conduct and/or interpret (due to the
requirement for multiple immobilizations for measurement of response), the
occurrence of non-specific results with methods such as the intradermal
skin test, and/or the near-total lack of validation, optimization and
standardization of any of the available test methods in the species of
interest. Additionally, because intradermal skin testing is the primary
screening method for many of these species, the ability to compare
exposure in captive wildlife with exposure in free-ranging populations has
been limited due to the difficulty with follow-up in free-ranging
populations. Lastly, unlike testing methods that use serological
techniques, skin testing precludes retrospective studies of banked samples
to determine onset of reactivity.
Recently, human tuberculosis researchers working with tuberculosis in
humans have developed an immunoassay that detects a serum protein complex
(the antigen 85, or Ag85, complex) produced by mycobacteria in the early
stages of mycobacterial infections1. Previous work has shown
that this method is a promising diagnostic tool in the evaluation of
tuberculosis exposure in some primate (including orangutan (Pongo
pygmaeus), a species known for non-specific tuberculin responses)2
and captive hoofstock species3. In order to determine the
feasibility and applicability of a widespread use of this method for
captive and free-ranging wildlife species, we have undertaken a number of
pilot studies on different populations of interest, with the goals of
optimizing and validating the immunoassay through analysis of serum from
known infected and non-infected individuals and through comparisons with
other diagnostic methods. Thus far, we have begun evaluating the
applicability of the antigen 85 immunoassay in various avian, primate,
rhinoceros and hoofstock species for detecting tuberculosis and/or
paratuberculosis (Johne's disease) infections. Preliminary results, a
summary of which will be presented, indicate that this method may be a
valuable adjunct to other testing methods (including gamma interferon and
multiple-antigen ELISA) to allow a better evaluation of true mycobacterial
status in these species.
1.Bentley-Hibbert, S. I., X. Quan, T. G. Newman, K. Huygen and H. P.
Godfrey. 1999. Pathophysiology of Antigen 85 in patients with active
tuberculosis. Infect Immun. 67(2):581-8.
2.Kilbourn, A. M., H. P. Godfrey, R. A. Cook, P. P. Calle, E. J. Bosi, S.
I. Bentley-Hibbert, K. Huygen, M. Andau, M. Ziccardi and W. B. Karesh.
2001. Serum Antigen 85 levels in adjunct testing for active mycobacterial
infections in orangutans. J. Wildl. Dis. 37(1): 65-71.
3.Mangold, B. J., R. A. Cook, M. R. Cranfield, K. Huygen, and H. P.
Godfrey. 1999. Detection of elevated levels of circulating antigen 85 by
dot immunobinding assay in captive wild animals with tuberculosis. J. Zoo
Wildl. Med. 30(4): 477-483.
12. Chandrasekharan,K. 2002. Specific
diseases of Asian elephants. Journal of Indian Veterinary Association
Abstract: The earliest writing describing the diseases of elephants in
ancient literature said to be the works on "Gajasastra" (Elephantology)
written in Sanskrit by authors like Gautama, Narada, Mrigacharma,
Rajaputra and Vyasa. "Hasthyayurveda" a legendary book in Sanskrit written
by a safe Palakapya deals with some diseases, treatment, desirable and
undesirable points of selection, management practices and some
mythological aspects on the origin of elephants. The earliest book in
English dealing with diseases of elephants seems to be that of W.
Gilchrist "A practical treatise on the treatment of diseases of elephants"
published in 1848. Later Slym (1873), Sanderson (1878), Steel (1885),
Evans (1910), Herpburn (1913), Milroy (1922), Ptaff (1940), Ferrier
(1947), Utoke Gale (1974), Chandrasekharan (1979) and Panicker (1985) have
documented their findings on the incidence, etiology and control of
diseases of Asian elephants.
13. Mikota,S.K. and Maslow,J. 2002.
Epidemiology and Treatment of Tuberculosis in Elephants: 2002. American
Association of Zoo Veterinarians Annual Conference, pp. 384-387.
14. Oh,P., Granich,R., Scott,J., Sun,B.,
Joseph,M., Stringfield,C., Thisdell,S., Staley,J., Workman-Malcolm,D.,
Borenstein,L., Lehnkering,E., Ryan,P., Soukup,J., Nitta,A., and Flood,J.
2002. Human exposure following Mycobacterium tuberculosis infection of
multiple animal species in a Metropolitan Zoo. Emerg Infect Dis
Abstract: From 1997 to 2000, Mycobacterium tuberculosis was diagnosed in
two Asian elephants (Elephas maximus), three Rocky Mountain goats (Oreamnos
americanus), and one black rhinoceros (Diceros bicornis) in the Los
Angeles Zoo. DNA fingerprint patterns suggested recent transmission. An
investigation found no active cases of tuberculosis in humans; however,
tuberculin skin-test conversions in humans were associated with training
elephants and attending an elephant necropsy.
15. Payeur,J.B., Jarnagin,J.L.,
Marquardt,J.G., and Whipple,D.L. 2002. Mycobacterial isolations in captive
elephants in the United States. Ann N Y Acad Sci 969:256-258.
Abstract: Interest in tuberculosis in elephants has been increasing over
the past several years in the United States. Several techniques have been
used to diagnose mammalian tuberculosis. Currently, the test considered
most reliable for diagnosis of TB in elephants is based on the culture of
respiratory secretions obtained by trunk washes.
16. Peloquin,CA. 2002. Therapeutic
drug monitoring in the treatment of tuberculosis. Drugs 62(15):2169-2183.
17. Turenne,C., Chedore,P., Wolfe,J.,
Jamieson,F., May,K., and Kabani,A. 2002. Phenotypic and molecular
characterization of clinical isolates of Mycobacterium elephantis from
human specimens. J Clin Microbiol 40(4):1230-1236.
Abstract: Eleven strains of a rapidly growing mycobacterium were isolated
from patient specimens originating from various regions of the province of
Ontario, Canada, over a 2-year period. Unique high-performance liquid
chromatography (HPLC) and PCR-restriction enzyme pattern analysis (PRA)
profiles initially suggested a new Mycobacterium species, while sequencing
of the 16S rRNA gene revealed a sequence match with Mycobacterium sp.
strain MCRO 17 (GenBank accession no. X93028), an isolate determined to be
unique which is to date uncharacterized, and also a close similarity to M.
elephantis (GenBank accession no. AJ010747), with six base pair
variations. A complete biochemical profile of these isolates revealed a
species of mycobacteria with phenotypic characteristics similar to those
of M. flavescens. HPLC, PRA, and 16S rRNA sequencing of strain M.
elephantis DSM 44368(T) and result comparisons with the clinical isolates
revealed that these strains were in fact M. elephantis, a newly described
species isolated from an elephant. All strains were isolated from human
samples, 10 from sputum and 1from an axillary lymph node.
Sauter-Louis,C.M., Lugton,I.W., Jacson,R., Durr,P.A., and Wilesmith,J.W.,
2001. Mycobacterial diseases. In Williams,E.S. (Editor). Infectious
Diseases of Wild Mammals.Ames, Iowa Iowa State University Press, pp.
19. Davis,M. 2001. Mycobacterium
tuberculosis risk for elephant handlers and veterinarians. Appl Occup
Environ Hyg 16(3):350-353.
20. Harr,K., Isaza,R., and Harvey,J.
2001. Clinicopathological findings in Mycobacterium tuberculosis
culture-positive elephants (Elephas maximus) in comparison to
clinically normal elephants. Proceedings American Association of Zoo
Veterinarians, American Association of Wildlife Veterinarians, Association
of Reptilian and Amphibian Veterinarians and the National Association of
Zoo and Wildlife Veterinarians Joint Conference 2001, pp. 209-211.
21. Isaza,R. 2001. The elephant trunk
wash - An update. ProcElephant Mangers Association Annual Conference.
22. 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., 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.
23. Montali,R.J., Mikota,S.K., and
Cheng,L.I. 2001. Mycobacterium tuberculosis in zoo and wildlife species.
Revue Scientifique et Technique Office International des Epizooties
Abstract: Tuberculosis caused by Mycobacterium tuberculosis, and M.
tuberculosis-like organisms has been identified in a wide range of
species: non-human primates, exotic ungulates and carnivores, elephants,
marine mammals, and psittacine birds. Disease associated with M.
tuberculosis has occurred mostly in captive settings and does not appear
to occur naturally in free-living mammals. Mycobacterium tuberculosis is
probably a zooanthroponosis of humans but from the zoonotic standpoint,
non-human primates, Asian elephants and psittacine birds have the
potential of transmitting this disease to humans. However, its overall
prevalence in these target species has been low and documented
transmissions of M. tuberculosis between animals and humans are uncommon.
M. tuberculosis causes progressive pulmonary disease in mammals and a
muco-cutaneous disease in parrots, and in all cases it can disseminate
and be shed into the environment. Diagnosis in living animals has been
based on intradermal tuberculin testing in non-human primates, culturing
trunk secretions in elephants, and biopsy and culture of external lesions
in parrots. Ancillary testing with DNA probes and nucleic acid
amplification, and enzyme-linked immunoabsorbent (ELISA) tests have been
adapted to some of these species with promising results. Additionally, new
guidelines for controlling tuberculosis in elephants in the U.S., and
programs for tuberculosis prevention in animal handlers have been
24. Ratanakorn,P. 2001. Elephant
Health Problems and Management in Cambodia, Lao and Thailand. A Research
Update on Elephants and Rhinos; Proceedings of the International Elephant
and Rhino Research Symposium, Vienna, June 7-11, 2001, pp. 111-114.
25. Larsen,R.S., Salman,M.D.,
Mikota,S.K., Isaza,R., Montali,R.J., and Triantis,J. 2000. Evaluation of a
multiple-antigen enzyme-linked immunosorbent assay for detection of
Mycobacterium tuberculosis infection in captive elephants. Journal of Zoo
and Wildlife Medicine 31(3):291-302.
Abstract: Mycobacterium tuberculosis has become an important agent of
disease in the captive elephant population of the United States, although
current detection methods appear to be inadequate for effective disease
management. This investigation sought to validate a multiple-antigen
enzyme-linked immunosorbent assay (ELISA) for screening of M. tuberculosis
infection in captive elephants and to document the elephant's serologic
response over time using a cross-sectional observational study design.
Serum samples were collected from 51 Asian elephants (Elephas maximus) and
26 African elephants (Loxodonta africana) from 16 zoos and circuses
throughout the United States from February 1996 to March 1999. Infection
status of each animal was determined by mycobacterial culture of trunk
washes. Reactivity of each serum sample against six antigens was
determined, and the linear combination of antigens that accurately
predicted the infection status of the greatest number of animals was
determined by discriminant analysis. The resulting classification
functions were used to calculate the percentage of animals that were
correctly classified (i.e., specificity and sensitivity). Of the 77
elephants sampled, 47 fit the criteria for inclusion in discriminant
analysis. Of these, seven Asian elephants were considered infected; 25
Asian elephants and 15 African elephants were considered noninfected. The
remaining elephants had been exposed to one or more infected animals. The
specificity and sensitivity of the multiple-antigen ELISA were both 100%
(91.9-100% and 54.4-100%, respectively) with 95% confidence intervals. M.
bovis culture filtrate showed the highest individual antigen specificity
(95%; 83.0-100%) and sensitivity (100%; 54.4-100%). Serum samples from 34
elephants were analyzed over time by the response to the culture filtrate
antigen; four of these elephants were culture positive and had been used
to calculate the discriminant function. Limitations such as sample size,
compromised ability to ascertain each animal's true infection status, and
absence of known-infected African elephants suggest that much additional
research needs to be conducted regarding the use of this ELISA. However,
the results indicate that this multiple-antigen ELISA would be a valuable
screening test for detecting M. tuberculosis infection in elephant herds.
26. Larsen,R.S., Salman,M.D.,
Mikota,S.K., Isaza,R., and Triantis,J. 2000. Validation and use of a
multiple-antigen ELISA for detection of tuberculosis infections in
elephants. Proc. AAZV and IAAAM Joint Conf., pp. 231-233.
27. Lyashchenko,K., Singh,M.,
Colangeli,R., and Gennaro,M.L. 2000. A multi-antigen print immunoassay for
the development of serological diagnosis of infectious disease. ournal of
Immunological Methods 242:91-100.
28. Mikota,S.K., Larsen,R.S., and
Montali,R.J. 2000. Tuberculosis in Elephants in North America. Zoo Biology
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.
29. Shojaei,H., Magee,J.G., Freeman,R.,
Yates,M., Horadagoda,N.U., and Goodfellow,M. 2000. Mycobacterium
elephantis sp. nov., a rapidly growing non-chromogenic Mycobacterium
isolated from an elephant. International Journal of Systematic and
Evolutionary Microbiology 50(5):1817-1820.
Abstract: A strain isolated from a lung abscess in an elephant that died
from chronic respiratory disease was found to have properties consistent
with its classification in the genus Mycobacterium. An almost complete
sequence of the 16S rDNA of the strain was determined following the
cloning and sequencing of the amplified gene. The sequence was aligned
with those available on mycobacteria and phylogenetic trees inferred by
using three tree-making algorithms. The organism, which formed a distinct
phyletic line within the evolutionary radiation occupied by rapidly
growing mycobacteria, was readily distinguished from members of validly
described species of rapidly growing mycobacteria on the basis of its
mycolic acid pattern and by a number of other phenotypic features, notably
its ability to grow at higher temperatures. The type strain is
Mycobacterium elephantis DSM 44368T. The EMBL accession number for the 16S
rDNA sequence of strain 484T is AJ010747.
30. Ziccardi,M., Mikota,S.K.,
Barbiers,R.B., and Norton,T.M. 2000. Tuberculosis in zoo ungulates:Survey
results and surveillance plan. Proc. AAZV and IAAAM Joint Conf., pp.
31. Bhat,M.N., Manickam,R., and
Ramkrishna,J. 1999. Screening of captive wild animals for tuberculosis.
Indian Veterinary Journal 76(11):959-961.
Abstract: The passive haemagglutination (PHA) test was used to test 109
captive elephants (Elephas maximus), and spotted deer (Cervus axis),
blackbuck (Antilope cervicapra) and common langurs (Semnopithecus
entellus?) (4 of each) for tuberculosis; 51 of the elephants and the 4
langurs were also assessed by the tuberculin test. PHA titres of 1:16 or
1:32 were found in 4 elephants, 1 deer and 2 langurs, but all were
apparently healthy except 1 langur that had clinical signs indicative of
tuberculosis. There were 4 positive reactors in the tuberculin tests, all
elephants, but these animals did not have significant PHA titres. It is
concluded that the procedures and reagents used for the diagnosis of
tuberculosis in domestic animals are not reliable for testing wild
32. Biberstein,E.L. and Hirsch,D.C.,
1999. Mycobacterium species: The agents of animal tuberculosis. In
Veterinary Microbiology.Maiden, MA Blackwell Science, pp. 158-172.
33. Isaza,R. and Ketz,C.J. 1999. A
Trunk Wash Technique for the Diagnosis of Tuberculosis in Elephants.
34. Mangold,B.J., Cook,R.A.,
Cranfield,M.R., Huygen,K., and Godfrey,H.P. 1999. Detection of elevated
levels of circulating antigen 85 by dot immunobinding assay in captive
wild animals with tuberculosis. Journal of Zoo and Wildlife Medicine
Abstract: Antemortem diagnosis of tuberculosis in captive wild animals is
often difficult. In addition to the variability of host cellular immune
response, which does not always indicate current active infection,
reactivity to saprophytic or other mycobacteria is common and may
interfere with the interpretation of the intradermal tuberculin skin test.
Furthermore, the immobilization required for administrating the test and
evaluating skin reactions in these animals may result in unacceptable
levels of morbidity and mortality, of particular concern in individuals of
rare or endangered species. Proteins of the antigen 85 (Ag85) complex are
major secretory products of actively metabolizing mycobacteria in vitro.
Production of these proteins by mycobacteria during growth in vivo could
result in increases in circulating levels of Ag85 in hosts with active
tuberculosis. A dot blot immunoassay has been used to detect and quantify
circulating Ag85 in captive wild animals with tuberculosis. Elevated
levels of Ag85 were observed in animals with active tuberculosis as
compared with uninfected animals. Study populations included a herd of
nyala (Tragelaphus angasi) (n=9) with no history of exposure to
Mycobacterium bovis. Serum Ag85 levels ranged from <5 to 15 uU/ml
(median, 5 uU/ml). The other group included 11 animals from a mixed
collection with a documented history of an M. bovis outbreak.
Animals with pulmonary granulomatous lesions (n=3) had serum Ag85 levels
ranging from 320 to 1,280 uU/ml (median, 320 uU/ml). Animals with only
chronic mediastinal or mesenteric lymphadenitis (n=4) had serum Ag85
levels ranging from <5 to 80 uU/ml (median, <5 uU/ml). This assay could
provide an important adjunct to intradermal skin testing for antemortem
diagnosis of tuberculosis in nondomestic species.
35. Mikota,S.K. 1999. Diseases of the
Elephant: A Review. Verh.ber.Erkrg.Zootiere 39:1-15.
36. Anonymous. 1998. TB in elephants.
37. Dunker,F. and Rudovsky,M. 1998.
Management and treatment of a Mycobacterium tuberculosis positive
elephant at the San Francisco Zoo. Proceedings AAZV and AAWV Joint
Conference, pp. 122-123.
38. Mahato,G., Rahman,H., Sharma,K.K.,
and Pathak,S.C. 1998. Tuberculin testing in captive Indian elephants (Elephas
maximus) of a national park. Indian Journal of Comparative Microbiology,
Immunology and Infectious Diseases 19(1):63.
Abstract: Full text:Tuberculosis, an important zoonotic disease, has been
reported in wild African and Asian domestic elephants (Seneviratna and
Seneviratna, 1966). Under this communication 25 cative Indian elephants of
Kaziranga National Park, Assam, were tested for allergic reaction by
injecting 0.1 ml PPD at the base of ear tip. The thickness of skin was
measured after 48 and 72 h and an increase of 4 mm or more was taken as
positive. Out of 25 elephants tested, 3 adults were found reactors. Base
of the ear was found more appropriate site as it remained protected from
rubbing against hard object due to irritation caused by the tuberculin and
needle. The trunk also could not disturb this inoculation site.
39. Michalak,K., Austin,C., Diesel,S.,
Bacon,M.J., Zimmerman,P., and Maslow,J.N. 1998. Mycobacterium tuberculosis
infection as a zoonotic disease: transmission between humans and
elephants. Emerg Infect Dis 4(2):283-287.
Abstract: Between 1994 and 1996, three elephants from an exotic animal
farm in Illinois died of pulmonary disease due to Mycobacterium
tuberculosis. In October 1996, a fourth living elephant was
culture-positive for M. tuberculosis. Twenty-two handlers at the farm were
screened for tuberculosis (TB); eleven had positive reactions to
intradermal injection with purified protein derivative. One had
smear-negative, culture-positive active TB. DNA fingerprint comparison by
IS6110 and TBN12 typing showed that the isolates from the four elephants
and the handler with active TB were the same strain. This investigation
indicates transmission of M. tuberculosis between humans and elephants.
40. Montali,R.J., Spelman,L.H.,
Cambre,R.C., Chattergee,D., and Mikota,S.K. 1998. Factors influencing
interpretation of indirect testing methods for tuberculosis in elephants.
Proceedings AAZV and AAWV Joint Conference, pp. 109-112.
Abstract: Serologic and other laboratory tests (such as BTB, ELISA, and
gamma interferon) are often used in conjunction with the intradermal
tuberculin test to detect tuberculosis (TB) in animals. The skin test is
considered the "gold standard" in domestic cattle and humans, and the BTB
test has been highly rated for use in cervid species. However, these
indirect methods for TB diagnosis have not been proven valid in most
exotic species susceptible to Mycobacterium tuberculosis complex
(which includes M. bovis) infection. In addition, many of the
tuberculin skin testing methods used in exotic species are not uniform in
terms of tuberculin type(s) and sites used and interpretation of the end
41. Binkley,M. 1997. Tuberculosis in
captive elephants. Proceedings American Association of Zoo Veterinarians,
42. Essey,M.A. and Davis,J.P. 1997.
Status of the National cooperative state-federal bovine tuberculosis
eradication program fiscal year 1997. Proceedings United States Animal
Health Association, pp. 564.
43. Furley,C.W. 1997. Tuberculosis in
elephants. Lancet British edition 350(9072):224.
Abstract: Tests on 171 elephants in zoos and circuses in the USA revealed
that 33% were positive to one or more skin tests and 11% were positive by
ELISA. As there is no standard procedure for testing elephants caution
should be used when interpreting the results.
44. Maslow,J. 1997. Tuberculosis and
other mycobacteria as zoonoses. Proceedings American Association of Zoo
Veterinarians, pp. 110-115.
Abstract: Mycobacterial infections are common among humans. Of theses,
infection with Mycobacterium tuberculosis (TB) is the most common
and of greatest concern. Non-tuberculous species of mycobacteria may also
cause infections in man, especially among immunosuppressed individuals.
Human TB is typically acquired by inhalation of aerosols carrying tubercle
bacilli fowwoing exposure to a person with active pulmonary infection;
non-tuberculous species of mycobacteria are acquired from environmental
sources. Since zoonotic transmission of TB does occur, the identification
of acid fast bacilli (AFB) in clinical specimens from animals is a cause
of concern, unease, and occasionally misconception for animal care
handlers and zoo personnel.
45. Mikota,S.K. and Maslow,J. 1997.
Theoretical and technical aspects of diagnostic techniques for mammalian
tuberculosis. Proceedings, American Association Zoo Veterinarians, pp.
46. Peloquin,CA. 1997. Using
therapeutic drug monitoring to dose the antimycobacterial drugs. Clinics
in Chest Medicine 18:79-97.
47. Whipple,D.L., Meyer,R.M.,
Berry,D.F., Jarnagin,J.L., and Payeur,J.B. 1997. Molecular epidemiology of
tuberculosis in wild white-tailed deer in michigan and elephants.
Proceedings One Hundred and First Annual Meeting of the United States
Animal Health Association, Louisville, Kentucky, USA, 18-24 October, 1997,
48. Dalovision,J.R., Montenegro-James,S.,
Kemmerly,S.A., Genre,C.F., Chambers,R., Pankey,G.A., Failla,D.M.,
Haydel,K.G., Hutchinson,L., Lindley,M.F., Praba,A., Eisenach,K.D., and
Cooper,E.S. 1996. Comparison of the amplified Mycobacterium tuberculosis (MTB)
direct test, aplicor MTB PCR and IS6, 110-PCR for detection of MTB in
respiratory specimens. Clin.Infect.Dis. 23:1099-1106.
49. Moda,G., Daborn,C.J., Grange,J.M.,
and Cosivi,O. 1996. The zoonotic importance of Mycobacterium bovis.
Tubercle and Lung Disease 77:103-108.
Abstract: The zoonotic importance of Mycobacterium bovis has been
the subject of renewed interest in the wake of the increasing incidence of
tuberculosis in the human population. This paper considers some of the
conditions under which transmission of M. bovis from animals to
humans occurs and reviews current information on the global distribution
of the disease. The paper highlights the particular threat posed by this
zoonotic disease in developing countries and lists the veterinary and
human public health measures that need to be adopted if the disease is to
contained. The association of tuberculosis with malnutrition and poverty
has long been recognized and the need to address these basic issues as as
crucial as specific measures against the disease itself.
50. Sandin,R.L. 1996. Polymerase chain
reaction and other amplification techniques in mycobacteriology. Clinical
Radhakrishnan,K., Cheeran,J.V., Nair,K.N.M., and Prabhakaran,T., 1995.
Review of the Incidence, Etiology and Control of Common Diseases of Asian
Elephants with Special Reference to Kerala. In Daniel,J.C. (Editor). A
Week with Elephants; Proceedings of the International Seminar on Asian
Elephants.Bombay, India Bombay Natural History Society; Oxford University
Press, pp. 439-449.
Abstract: Incidence, etiology, symptoms and control of specific and
non-specific diseases of captive and wild elephants have been reviewed.
Asian elephants have been observed to be susceptible to various parasitic
diseases such as helminthiasis, trypanosomiasis and ectoparasitic
infestations, bacterial diseases such as tetanus, tuberculosis,
haemorrhagic septicemia, salmonellosis and anthrax, viral diseases such as
foot and mouth disease, pox and rabies and non-specific diseases like
impaction of colon, foot rot and corneal opacity. A detailed study
extending over two decades on captive and wild elephants in Kerala,
revealed high incidence of helminthiasis (285), ectoparasitic infestation
(235), impaction of colon (169) and foot rot (125). Diseases such as
trypanosomiasis (21), tetanus (8), tuberculosis (5) pox (2) and anthrax
(1) were also encountered. The line of treatment against the diseases
mentioned, have been discussed in detail.
52. 1994. Treatment of tuberculosis
and tuberculosis infection in adults and children. Am J Respir Crit Care
53. Chandrasekharan,K., 1992.
Prevalence of infectious diseases in elephants in Kerala and their
treatment. In Silas,E.G., Nair,M.K., and Nirmalan,G. (Editors). The Asian
Elephant: Ecology, Biology, Diseases, Conservation and Management
(Proceedings of the National Symposium on the Asian Elephant held at the
Kerala Agricultural University, Trichur, India, January 1989).Trichur,
India Kerala Agricultural University, pp. 148-155.
54. Fowler,M.E. 1991. Tuberculosis in
zoo ungulates. Bovine tuberculosis in cervidae: Proceedings of a
symposium, pp. 37-41.
55. Ilnitskii,I.G. 1991.
Chemo-tuberculin therapy in association with tissue electrophoresis in the
management of patients with recently detected destructive pulmonary
tuberculosis. Vrach.Delo. 0(11):59-61.
56. John,M.C., Nedunchelliyan,S., and
Raghvan,N. 1991. Tuberculin testing in Indian elephants. Indian Journal of
Veterinary Medicine 11(1-2):48-49.
57. Thoen,C.O. 1988. Tuberculosis.
Journal of the American Veterinary Medical Association 193(9):1045-1048.
58. Arora,B.M. 1986. Tuberculosis in
wildlife in India. Summer Institute on Health, Production and Management
in Wildlife, pp. 67-78.
59. Snider,D.E., Jr., Jones,W.D., and
Good,R.C. 1984. The usefulness of phage typing Mycobacterium
tuberculosis isolates. Am.Rev.Respir.Dis. 130:1095-1099.
Abstract: Mycobacteriophage typing of Mycobacterium tuberculosis isolates
was used as an epidemiologic aid in investigating the transmission of
tuberculosis in community, industrial, and institutional outbreaks. The
technique was also useful in other situations, e.g., documenting
congenital transmission of infection and distinguishing exogenous
reinfection from endogenous reactivation. Additional studies are indicated
to further explore the value of phage typing for tracking the transmission
of tuberculosis in the community
60. Devine,J.E., Boever,W.J., and
Miller,E. 1983. Isoniazid therapy in an Asiatic elephant (Elephas
maximus). Journal of Zoo and Wildlife Medicine 14:130-133.
61. Saunders,G. 1983. Pulmonary
Mycobacterium tuberculosis infection in a circus elephant. Journal of
the American Veterinary Medical Association 183(11):1311-1312.
62. Wallach,J.D. and Boever,W.J.,
1983. Tuberculosis. In Diseases of Exotic Animals. pp. 791-792.
63. Jones,W.D., Jr. and Good,R.C.
1982. Hazel elephant redux (letter). Am.Rev.Respir.Dis. 125(2):270.
Abstract: Full text. A recent letter from Greenberg, Jung and Gutter
reported the untimely death of Hazel Elephant with Mycobacterium
tuberculosis infection. The authors concluded that the animal
trainer, who was found to have cavitary tuberculosis, was probably the
source of infection. The conclusion was based on data available at the
time. The isolates from Hazel Elephant and the animal trainer were
submitted to us for further study the state health departments of
Louisiana and Florida. Using the methodology and classification scheme
previously described, we found that the cultures were of different phage
types. The isolate from the elephant was type A0 (7), and the
isolate from the trainer was type A1 (7,13,14). The isolates
differed by lysis with one major phage (MTPH 5) and two auxiliary phages (MTPH
13 and 14). We have previously used phage typing of M. tuberculosis
in several well-defined outbreaks as an adjunct to other epidemiologic
procedures. The isolates were typed without the laboratory's knowing
epidemiologic relationships between cases. The results indicated that
M. tuberculosis transmitted from one individual to another retained
the same phage-type characteristics. In the present study, our phage-type
results suggest that the animal trainer and the elephant were infected
from two different sources and that occurrence of disease in the animal
and the trainer was coincidental. We are still evaluating page typing as
a procedure for use in tuberculosis epidemiology and can accept selected
cultures for phage typing in special situations if we are contacted before
the cultures are submitted.
64. Woodford,M.H. 1982. Tuberculosis
in wildlife in the Ruwenzori National Park, Uganda (Part II).
Abstract: The results of post-mortem examinations of 90 warthog (Phacochoerus
aethiopicus) conducted in the Ruwenzori National Park, Uganda during a
survey of tuberculous infection in wildlife are described. Nine per cent
of warthog were found to show gross lesions on autopsy and of these
organisms which could by typed, Mycobacterium bovis was isolated in 2 of 6
cases and 5 atypical mycobacterial strains were isolated from the
remaining 4. The distribution and character of the lesions is described
and it is concluded that the route of infection in the warthog is
alimentary. A mycobacterial survey of 8 other species of mammals, 7
species of birds, 5 species of fish and 1 species of amphibian is
described. None of the mammals (except possibly 1 elephant), birds, fish
or amphibia was harbour atypical, probably saprophytic, mycobacterial
types. The origin of tuberculosis in buffalo and warthog in the Ruwenzori
National Park is discussed and is concluded to have been previous contact
with domestic cattle.
65. Greenberg,H.B., Jung,R.C., and
Gutter,A.E. 1981. Hazel Elephant is dead (of tuberculosis) (letter).
Abstract: Full text. Hazel Elephant was only 35 years old (by our
estimate) when she died. She was cooperative and trusting to the last.
Had we known about her illness sooner, we could have saved her. The
Mycobacterium tuberculosis, var hominis that killed Hazel was
sensitive to our drugs at the following levels: INH to 0.2mcg/ml; PAS to 2
mcg/ml; R to 1 mcg/ml; and MAB to 5 mcg/ml. Hazel worked and performed
for a travelling circus. Ordinarily good-humored and loving, she had been
off her feed for weeks. She became listless and apathetic, her eyes lost
their sparkle, and she lacked her customary elan. Nonetheless, Hazel
continued to perform for the children and do her other chores until she
came to New Orleans. When Hazel got to New Orleans, she could barely
move. The circus's bosses called for help. The brought her to the
hospital at the Audubon Park and Zoological Garden. As soon as we saw
Hazel, we admitted her to the isolation ward. We have her fluids,
electrolytes, and antibiotics. We got cultures and other clinical
laboratory tests. We comforted Hazel and tried to put her at ease. It
was too late. She fell to the ground, her rheumy eyes gazed at us
pitifully, her respirations failed, and she died. Hazel's postmortem
examination took six hours. She was an emaciated Asian elephant whose
lungs were filled with caseating granulomata. Since microscopy showed
myriads of acid-fast bacilli, we examined everyone who had, or who thought
they had, contact with Hazel. We found three persons with positive
tuberculin skin test results. None had tuberculous disease. Fortunately,
Hazel had been kept away from other animals. Hazel's circus did not wait
for the results of our autopsy. It left Louisiana. The U.S. Public
Health Service tracked it down and found the man, an animal trainer with
cavitary tuberculosis, who probably gave Hazel her fatal disease. Now
another health department will have to deal with the circus and its
66. Gutter,A. 1981. Mycobacterium
tuberculosis in an Asian elephant. Proc.Am.Assoc.Zoo Vet., pp. 105-106.
67. Mann,P.C., Bush,M., Janssen,D.L.,
Frank,E.S., and Montali,R.J. 1981. Clinicopathologic correlations of
tuberculosis in large zoo mammals. Journal of the American Veterinary
Medical Association 179(11):1123-1129.
Abstract: In August 1978, a black rhinoceros at the National Zoological
Park died with generalized tuberculosis caused by Mycobacterium bovis. A
2nd black rhinoceros was euthanatized 9 months after M bovis was cultured
from its lungs. After these 2 deaths, numerous large zoo mammals that had
been potentially exposed were subjected to various procedures to ascertain
their status regarding tuberculosis. The procedures were: intradermal
tuberculin testing, evaluation of delayed hypersensitivity reaction on
biopsy specimens, enzyme-linked immunosorbent assay (ELISA) testing, and
culture of various secretions and organs. Several of the animals in this
series died during the study. These were necropsied and examined for
evidence of mycobacterial infection. The results of tuberculin testing
varied from species to species and from site to site within a species.
Delayed hypersensitivity responses generally correlated well with the
amount of swelling at the tuberculin site. In some cases, however,
positive reactions were found without any delayed hypersensitivity
response. Results of ELISA testing were confirmatory in tuberculous
animals. Several species were judged to be nonspecific reactors, based on
positive or suspect tuberculin test results, with negative ELISA results
and necropsy findings.
68. Thoen,C.O. and Himes,E.M., 1981.
Tuberculosis. In Davis,J.W., Karstad,L.H., and Trainer,D.O. (Editors).
Infectious diseases of wild mammals.Ames, Iowa The University of Iowa
69. Thoen,C.O., Mills,K., and
Hopkins,M.P. 1980. Enzyme linked protein A: An enzyme-linked immunosorbent
assay reagent for detecting antibodies in tuberculous exotic animals.
American Journal of Veterinary Research 41(5):833-835.
Abstract: An enzyme-linked immunosorbent assay (ELISA) was developed,
using protein A labeled with horseradish peroxidase for detecting
antibodies in tuberculous exotic animals (llamas, rhinoceroses,
elephants). The modified ELISA provides a rapid procedure for screening
several animal species simultaneously for tuberculosis without the
production of specific anti-species conjugates. Heat-killed cells of
Mycobacterium bovis and M. avium and purified
protein-derivative tuberculin of M. bovis were used as antigens for
70. Thoen,C.O. and Himes,E.M., 1980.
Mycobacterial infections in exotic animals. In Montali,R.J. and Migaki,G.
(Editors). The comparative pathology of zoo animals.Washington,D.C.
Smithsonian Institution Press, pp. 241-245.
Abstract: Mycobacteria were isolated from 59% of the 826 specimens
submitted from exotic animals suspected of having tuberculosis.
Mycobacterium bovis and Mycobacterium tuberculosis accounted
for 61% of the isolations from nonhuman primates. Mycobacterium bovis
was the organism most frequently isolated from hoofed animals and
Mycobacterium avium was most commonly isolated from birds. The
distribution, pathogenesis, diagnosis, and control of tuberculosis in
exotic animals is discussed.
71. Chandrasekharan,K. 1979. Common
diseases of elephants. State Level Workshop on Elephants, pp. 51-61.
72. Thoen,C.O., Richards,W.D., and
Jarnagin,J.L. 1977. Mycobacteria isolated from exotic animals. Journal of
the American Veterinary Medical Association 170(9):987-990.
73. von Benten,K., Fiedler,H.H.,
Schmidt,U., Schultz,L.C., Hahn,G., and Dittrich,L. 1975. Occurrence of
tuberculosis in zoo mammals; a critical evaluation of autopsy material
from 1970 to the beginning of 1974. Deutsche Tierarztliche Wochenschrift
74. Pinto,M.R.M., Jainudeen,M.R., and
Panabokke,R.G. 1973. Tuberculosis in a domesticated Asiatic elephant
Elephas maximus. Veterinary Record 93(26):662-664.
Abstract: A case of tuberculosis in a domesticated Asiatic elephant,
Elephas maximus, was diagnosed on post-mortem examination. The
causal organism was identified as Mycobacterium tuberculosis var
hominis on the basis of cultural, biochemical and virulence studies.
Microscopically, the lesions resembled tuberculous lesions as seen in man
and other domestic animals, but an important difference was the apparent
absence of Langerhan's type giant cells. The problems associated with the
clinical diagnosis of tuberculosis in the elephant are discussed.
75. Gorovitz,C. 1969. Tuberculosis in
an African elephant. American Association of Zoo Veterinarians Newsletter
76. Seneviratna,P., Wettimuny,S.G.,
and Seneviratna,D. 1966. Fatal tuberculosis pneumonia in an elephant.
Veterinary Medicine Small Animal Clinician 60:129-132.
Abstract: A fatal case of tuberculosis pneumonia with anemia and
helminthiasis in a Ceylon elephant is reported. Acid-fast organisms
resembling Mycobacterium tuberculosis and tubercular nodules were
seen in large numbers in sections of the lung.
77. Gorovitz,C. 1962. Tuberculosis in
an African elephant. Nord Vet Med 14(Supl 1):351-352.
78. Halloran,P.O. 1955. A bibliography
of references to diseases in wild mammals and birds. American Journal of
Veterinary Research 16(part 2):161.
79. Curasson,G., 1942. Traite de
pathologie exotique veterinaire et comparee. Vigot Freres, Paris.
80. Griffith,A.S. 1939. Infections of
wild animals with tubercle and other acid-fast bacilli. Proceedings of the
Royal Society of Medicine 32:1405-1412.
81. Urbain,A. 1938. Tuberculosis in
wild animals in captivity. Annales de L'Institute Pasteur 61:705-730.
82. Winogradradsky,S. 1938. La
microbiologie ecologique ses principes - son procede. Annales de
L'Institute Pasteur 64(6):715-730.
83. Iyer,A.K. 1937. Veterinary science
in India, ancient and modern with special reference to tuberculosis.
84. Curasson,G., 1936. Treatise on the
pathology of exotic animals. Vigot Freres, Paris.
85. Datta,S.C.A. 1934. Report of the
pathology section. Ann.Rep.Imp.Inst.Vet.Research Muktesar:25-33.
86. Baldrey,F.S.H. 1930. Tuberculosis
in an elephant. J.R.Army Vet.Corp. 1:252.
87. Bopayya,A.B. 1928. Tuberculosis in
an elephant. Indian Veterinary Journal 5:142-145.
88. Narayanan,R.S. 1925. A case of
tuberculosis in an elephant. Journal of Comparative Pathology 38:96-97.
89. Thieringer,H. 1911. About
tuberculosis in an elephant. Berl.Tierarztl.Wschr. 27:234-235.
90. Damman and Stedefeder. 1909.
Tuberculosis diseases in elephants with human type mycobacterium. Deutsche
Tierarztliche Wochenschrift 17:345.
91. Garrod,A.H. 1875. Report on the
Indian elephant which died in the society's gardens on July 7th, 1875.
Procedings of the Zoological Society of London 1875:542-543.