Elephant
Bibliographic
Database

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Elephant Bibliographic Database
www.elephantcare.org

References updated October 2009 by date of publication, most recent first.

2009. Methicillin-resistant Staphylococcus aureus skin infections from an elephant calf--San Diego, California, 2008
91. MMWR Morb. Mortal. Wkly. Rep. 58, 194-198.
Abstract: Methicillin-resistant Staphylococcus aureus (MRSA) infections are a major cause of human skin and soft tissue infections in the United States. MRSA colonization and infection also have been observed in turtles, bats, seals, sheep, rabbits, rodents, cats, dogs, pigs, birds, horses, and cattle, and MRSA infections with an epidemiologic link to animal contact have been reported in veterinary personnel, pet owners, and farm animal workers. On January 29, 2008, the County of San Diego Health and Human Services Agency was notified of skin pustules on an African elephant (Loxodonta africana) calf and three of its caretakers at a zoo in San Diego County. After each of these infections (including the calf's infection) was laboratory confirmed as MRSA, an outbreak investigation and response was initiated by the zoo and the agency. This report summarizes the results of that investigation, which identified two additional confirmed MRSA infections, 15 suspected MRSA infections, and three MRSA-colonized persons (all among calf caretakers), and concluded that infection of the elephant calf likely came from a colonized caretaker. This is the first reported case of MRSA in an elephant and of suspected MRSA transmission from an animal to human caretakers at a zoo. Recommendations for preventing MRSA transmission in zoo settings include 1) training employees about their risks for infection and the recommended work practices to reduce them; 2) performing proper hand hygiene before and after animal contact; 3) using personal protective equipment (PPE) when working with ill or infected animals, especially during wound treatment; and 4) cleaning and disinfecting contaminated equipment and surfaces

Chinnadurai, S.K., Suedmeyer, W.K., Fales, W.H., 2009. Microbiology of the external ear canal in six African elephants (Loxodonta africana)
99. Veterinary Record 164, 238-240.
Abstract: Samples collected from both external ear canals of six adult female African elephants (Loxodonta africana) were cultured for fungi, yeasts and aerobic and anaerobic bacteria. All the samples produced heavy growths of several aerobic bacteria, but anaerobic bacteria were rare and no fungi or yeasts were isolated. The most common bacterium isolated was Staphylococcus epidermidis, which was cultured from 11 of the 12 ears. Acinetobacter calcoaceticus lwoffi, alpha-haemolytic Streptococcus and Corynebacterium species, and Aeromonas caviae were all isolated from at least six of the 12 ears

Greenwald, R., Lyashchenko, O., Esfandiari, J., Miller, M., Mikota, S., Olsen, J.H., Ball, R., Dumonceaux, G., Schmitt, D., Moller, T., Payeur, J.B., Harris, B., Sofranko, D., Waters, W.R., Lyashchenko, K.P., 2009. Highly accurate antibody assays for early and rapid detection of tuberculosis in African and Asian elephants. Clin. Vaccine Immunol. 16, 605-612.
Abstract: Tuberculosis (TB) in elephants is a reemerging zoonotic disease caused primarily by Mycobacterium tuberculosis. Current methods for screening and diagnosis rely on trunk wash culture, which has serious limitations due to low test sensitivity, slow turnaround time, and variable sample quality. Innovative and more efficient diagnostic tools are urgently needed. We describe three novel serologic techniques, the ElephantTB Stat-Pak kit, multiantigen print immunoassay, and dual-path platform VetTB test, for rapid antibody detection in elephants. The study was performed with serum samples from 236 captive African and Asian elephants from 53 different locations in the United States and Europe. The elephants were divided into three groups based on disease status and history of exposure: (i) 26 animals with culture-confirmed TB due to M. tuberculosis or Mycobacterium bovis, (ii) 63 exposed elephants from known-infected herds that had never produced a culture-positive result from trunk wash samples, and (iii) 147 elephants without clinical symptoms suggestive of TB, with consistently negative trunk wash culture results, and with no history of potential exposure to TB in the past 5 years. Elephants with culture-confirmed TB and a proportion of exposed but trunk wash culture-negative elephants produced robust antibody responses to multiple antigens of M. tuberculosis, with seroconversions detectable years before TB-positive cultures were obtained from trunk wash specimens. ESAT-6 and CFP10 proteins were immunodominant antigens recognized by elephant antibodies during disease. The serologic assays demonstrated 100% sensitivity and 95 to 100% specificity. Rapid and accurate antibody tests to identify infected elephants will likely allow earlier and more efficient treatment, thus limiting transmission of infection to other susceptible animals and to humans

Greenwald, R., Lyashchenko, O., Esfandiari, J., Miller, M., Mikota, S., Olsen, J.H., Ball, R., Dumonceaux, G., Schmitt, D., Moller, T., Payeur, J.B., Harris, B., Sofranko, D., Waters, W.R., Lyaschenko, K.P., 2009. Highly accurate antibody assays for early and rapid detection of tuberculosis in African and Asian elephants. Clinical and Vaccine Immunology 16, 605-612.
Abstract: Tuberculosis (TB) in elephants is a reemerging zoonotic disease caused primarily by Mycobacterium tuberculosis. Current methods for screening and diagnosis rely on trunk wash culture, which has serious limitations due to low test sensitivity, slow turnaround time, and variable sample quality. Innovative and more efficient diagnostic tools are urgently needed. We describe three novel serologic techniques, the ElephantTB Stat-Pak kit, multiantigen print immunoassay, and dual-path platform VetTB test, for rapid antibody detection in elephants. The study was performed with serum samples from 236 captive African and Asian elephants from 53 different locations in the United States and Europe. The elephants were divided into three groups based on disease status and history of exposure: (i) 26 animals with culture-confirmed TB due to M. tuberculosis or Mycobacterium bovis, (ii) 63 exposed elephants from known-infected herds that had never produced a culture-positive result from trunk wash samples, and (iii) 147 elephants without clinical symptoms suggestive of TB, with consistently negative trunk wash culture results, and with no history of potential exposure to TB in the past 5 years. Elephants with culture-confirmed TB and a proportion of exposed but trunk wash culture-negative elephants produced robust antibody responses to multiple antigens of M. tuberculosis, with seroconversions detectable years before TB-positive cultures were obtained from trunk wash specimens. ESAT-6 and CFP10 proteins were immunodominant antigens recognized by elephant antibodies during disease. The serologic assays demonstrated 100% sensitivity and 95 to 100% specificity. Rapid and accurate antibody tests to identify infected elephants will likely allow earlier and more efficient treatment, thus limiting transmission of infection to other susceptible animals and to humans.

Jantou, V., Turmaine, M., West, G.D., Horton, M.A., McComb, D.W., 2009. Focused ion beam milling and ultramicrotomy of mineralised ivory dentine for analytical transmission electron microscopy
114. Micron. 40, 495-501.
Abstract: The use of focused ion beam (FIB) milling for preparation of sections of mineralised ivory dentine for transmission electron microscopy (TEM) is investigated. Ivory dentine is essentially composed of fibrillar type-I collagen and apatite crystals. The aim of this project is to gain a clearer understanding of the relationship between the organic and inorganic components of ivory dentine using analytical TEM, in order to utilise these analytical techniques in the context of common skeletal diseases such as osteoporosis and arthritis. TEM sections were prepared in both single and dual beam FIB instruments, using two standard lift-out techniques, in situ and ex situ. The FIB sections were systematically compared with sections prepared by ultramicrotomy, the traditional preparation route in biological systems, in terms of structural and chemical differences. A clear advantage of FIB milling over ultramicrotomy is that dehydration, embedding and section flotation can be eliminated, so that partial mineral loss due to dissolution is avoided. The characteristic banding of collagen fibrils was clearly seen in FIB milled sections without the need for any chemical staining, as is commonly employed in ultramicrotomy. The FIB milling technique was able to produce high-quality TEM sections of ivory dentine, which are suitable for further investigation using electron energy-loss spectroscopy (EELS) and energy-filtering TEM (EFTEM) to probe the collagen/apatite interface

Lindsay, W.A., Wiedner, E., Isaza, R., Townsend, H.G., Boleslawski, M., Lunn, D.P., 2009. Immune responses of Asian elephants (Elephas maximus) to commercial tetanus toxoid vaccine. Vet. Immunol. Immunopathol.
Abstract: Although captive elephants are commonly vaccinated annually against tetanus using commercially available tetanus toxoid vaccines marketed for use in horses and livestock, no data exists to prove that tetanus toxoid vaccination produces measurable antibody titers in elephants. An ELISA test was created to measure antibody responses to tetanus toxoid vaccinations in 22 Asian elephants ranging in age from 24 to 56 years (mean age 39 years) over a 7-month period. All animals had been previously vaccinated with tetanus toxoid vaccine, with the last booster administered 4 years before the start of the study. The great majority of elephants had titers prior to booster vaccination, and following revaccination all elephants demonstrated anamnestic increases in titers, indicating that this species does respond to tetanus vaccination. Surprisingly older animals mounted a significantly higher response to revaccination than did younger animals.

Aupperle, H., Reischauer, A., Bach, F., Hildebrandt, T., Goritz, F., Jager, K., Scheller, R., Klaue, H.J., Schoon, H.A., 2008. Chronic endometritis in an Asian elephant (Elephas maximus). J. Zoo. Wildl. Med. 39, 107-110.
Abstract: A 48-yr-old female Asian elephant with a history of pododermatitis developed recurrent hematuria beginning in 2002. Transrectal ultrasonography and endoscopic examination in 2004 identified the uterus as the source of hematuria and excluded hemorrhagic cystitis. Treatment with Desloreline implants, antibiotics, and homeopathic drugs led to an improved general condition of the elephant. In July 2005, the elephant was suddenly found dead. During necropsy, the severely enlarged uterus contained about 250 L of purulent fluid, and histopathology revealed ulcerative suppurative endometritis with high numbers of Streptococcus equi ssp. zooepidemicus and Escherichia coli identified on aerobic culture. Additional findings at necropsy included: multifocal severe pododermatitis, uterine leiomyoma, and numerous large calcified areas of abdominal fat necrosis. Microbiologic culture of the pododermatitis lesion revealed the presence of Streptococcus agalactiae, Streptococcus equi ssp. zooepidemicus, Staphylococcus sp., Corynebacterium sp., and Entercoccus sp

Meyers, D.A., Isaza, R., MacNeill, A. Evaluation of acute phase proteins for diagnosis of inflammation in Asian elephants ( Elephas maximus). Proc American Associaton of Zoo Veterinarians and Assoc of Reptile and Amphibian Veterinarians.  128. 2008. 11-10-2008.
Ref Type: Conference Proceeding
Abstract: In many domestic species, routine hematology assays are useful diagnostic tools to diagnose inflammatory conditions. Unlike other species, these hematologic tests apparently are insensitive indicators of inflammation in elephants.1 We studied a novel group of blood proteins, called acute phase proteins, which increase during inflammatory conditions, for their usefulness in diagnosing elephants with inflammatory diseases. Although these proteins currently are useful in humans and domestic animals, each species has a different set of important proteins that must be individually investigated.2 We tested several acute phase proteins (C-reactive protein, alpha-1 glycoprotein, alpha-1 antitrypsin, serum amyloid A, haptoglobin, fibrinogen, ceruloplasmin, and albumin) as well as complete blood counts, chemistry panels, serum protein electrophoresis, and 3-D gel electrophoresis to determine their usefulness for diagnosing different types of inflammatory conditions in Asian elephants (Elephas maximus). Animals with inflammatory conditions were classified as those individuals with known illnesses such as mycobacteriosis, arthritis, nail bed abscesses, and malignant tumors. Control animals were thoseanimals that were suspected to not have any inflammation and be healthy at the time of testing as determined by physical examination and obtaining a thorough medical history.
LITERATURE CITED
1. Lyashchenko, K., R. Greenwald, J. Esfandiari, J. Olsen, R. Ball, G. Dumonceaux, F. Dunker, C. Buckley, M.
Richard, S. Murray, J.B. Payeur, P. Anderson, J.M. Pollock, S. Mikota, M. Miller, D. Sofranko, and W.R.
Waters. 2006. Tuberculosis in Elephants: Antibody responses to defined antigens of Mycobacterium
tuberculosis, potential for early diagnosis, and monitoring of treatment. Clin. Vacc. Immunol. 13: 722-732.
2. Murata H., N. Shimada, M. Yoshioka. 2004. Current research on acute phase proteins in veterinary diagnosis:
an overview. Vet J. 168: 28-40.

Mikota, S.K., 2008. Tuberculosis in elephants. In: Fowler, M.E., Miller, R.E. (Eds.), Zoo and Wild Animal Medicine, Current Therapy 6th edition. Saunders/Elsevier, St. Louis, pp. 355-364.

Miller, J., McClean, M. Pharmacokinetics of enrofloxacin in African elephants (Loxodonta africana) after a single rectal dose. Proc American Associaton of Zoo Veterinarians and Assoc of Reptile and Amphibian Veterinarians.  224-225. 2008. 11-10-2008.
Ref Type: Conference Proceeding
Abstract: Captive African elephants (Loxodonta Africana) are susceptible to many types of gram negative bacterial infections such as Escherichia coli, Mycoplasma  spp., Salmonella spp., Klebsiella spp., Pseudomonas spp., and Proteus spp. Enrofloxacin (Baytril®, Bayer Health Care, Animal Health Division, P.O. Box 390, Shawnee Mission, KS 66201) is a potentially effective antibiotic for
treatment of these bacterial infections in elephants. Very limited data exists on the pharmacokinetics of enrofloxacin in elephants2 and most of the dosage regimes for gastrointestinal absorption are based on horse dosages since they share a similar  gastrointestinal tract. Three African elephants from Wildlife Safari in Winston, Oregon, two females both 37-yr-old and one male 26-yr-old, were used to determine whether therapeutic levels of enrofloxacin could be achieved thru rectal administration of liquid injectable enrofloxacin (Baytril 100®, 100 mg/ml, Bayer Health Care, Animal Health Division, P.O. Box 390, Shawnee Mission, KS 66201) at a dosage of 2.5 mg/kg. A pretreatment baseline blood sample was collected. Following administration, blood samples were collected at 45 min, 1.5hr, 2.5hr, 5hr, 9hr, 23hr, 36hr to determine plasma enrofloxacin levels. Plasma enrofloxacin levels were measured at North Carolina State University, College of Veterinary Medicine using high performance liquid chromatography (HPLC) analysis. Plasma ciprofloxacin levels were measured concurrently. Results indicate plasma concentrations of enrofloxacin did not reach adequate bacteriocidal levels for any of the the following common bacterial isolates in captive elephants: Mycoplasma
spp., Escherichia coli, Salmonella spp., Klebsiella spp., Pseudomonas spp., and Proteus spp. The study determined that a rectally administered dosage of 2.5 mg/kg of liquid injectable enrofloxacin was insufficient to obtain therapeutic levels in African elephants. The low plasma levels of enrofloxacin in all three elephants may be a result of poor absorption in the distal large intestine. A future study will determine if oral administration will provide a more efficient mode of drug delivery and absorption in African elephants. It is also possible that the current dosage of 2.5 mg/kg is too low to achieve adequate therapeutic levels.
ACKNOWLEDGMENTS
I would like to thank the elephant and veterinary staff at Wildlife Safari for their participation in conducting this study. Thanks to Doctors: Modesto McClean, Jason Bennett, Andi Chariffe, Tessa Lohe, Benji Alacantar. Also thanks to Dinah Wilson, Carol Matthews, Anthony Karels, Mary Iida, Shawn Finnell, Patches Stroud, Katie Alayan.
LITERATURE CITED
1. Haines, G.R., et. al. 2000. Serum concentrations and pharmacokinetics of enrofloxacin after intravenous and intragastric administration to mares. Can. J.Vet. Res. 64(3):171-177.
2. Sanchez, C.R., et. al. 2005. Pharmacokinetics of a single dose of enrofloxacin administered orally to captive Asian elephants (Elephas maximus). Am. J. Vet. Res. 66:1948-1953.

Helke, K.L., Mankowski, J.L., Manabe, Y.C., 2007. Animal models of cavitation in pulmonary tuberculosis. Tuberculosis (Edinb) 86, 337-348.
Abstract: Transmission of tuberculosis occurs with the highest frequency from patients with extensive, cavitary, pulmonary disease and positive sputum smear microscopy. In animal models of tuberculosis, the development of caseous necrosis is an important prerequisite for the formation of cavities although the immunological triggers for liquefaction are unknown. We review the relative merits and the information gleaned from the available animal models of pulmonary cavitation. Understanding the host-pathogen interaction important to the formation of cavities may lead to new strategies to prevent cavitation and thereby, block transmission.

Lacasse, C., Terio, K., Kinsel, M.J., Farina, L.L., Travis, D.A., Greenwald, R., Lyashchenko, K.P., Miller, M., Gamble, K.C., 2007. Two cases of atypical mycobacteriosis caused by Mycobacterium szulgai associated with mortality in captive African elephants (Loxodonta africana). J. Zoo. Wildl. Med. 38, 101-107.
Abstract: Mycobacterium szulgai was associated with mortality in two captive African elephants (Loxodonta africana) housed at Lincoln Park Zoo. The first elephant presented with severe, acute lameness of the left rear limb. Despite extensive treatments, the animal collapsed and died 13 mo after initial presentation. Necropsy revealed osteomyelitis with loss of the femoral head and acetabulum and pulmonary granulomas with intralesional M. szulgai. The second elephant collapsed during transport to another institution with no premonitory clinical signs. This animal was euthanized because of prolonged recumbency. Granulomatous pneumonia with intralesional M. szulgai was found at necropsy. Two novel immunoassays performed on banked serum samples detected antibody responses to mycobacterial antigens in both infected elephants. It was not possible to determine when the infection was established or how the elephants were infected. When reviewing the epidemiology of this organism in humans, however, transmission between elephants seemed unlikely because human-to-human transmission of this organism has never been reported and a third elephant in the herd was not affected. In addition to Mycobacterium bovis and Mycobacterium tuberculosis, atypical mycobacterial organisms need to be considered potentially pathogenic in elephants

Oni, O., Sujit, K., Kasemsuwan, S., Sakpuaram, T., Pfeiffer, D.U., 2007. Seroprevalence of leptospirosis in domesticated Asian elephants (Elephas maximus) in north and west Thailand in 2004. Veterinary Record 160, 368-371.
Abstract: Serum samples from Asian elephants (Elephas maximus) in the Kanchanaburi, Chiang Mai and Lampang provinces of Thailand were tested using the microscopic agglutination test against 22 serovars of Leptospira interrogans. A titre of more than 1:100 was used as evidence of infection. In northern Thailand, the seroprevalence was 58 per cent and the prevalent serovars were Leptospira interrogans serovar Sejroe, Leptospira interrogans serovar Tarassovi, Leptospira interrogans serovar Ranarum and Leptospira interrogans serovar Shermani. In western Thailand, the seroprevalence was 57 per cent and the prevalent serovars were L Tarassovi, L Sejroe, L Ranarum, Leptospira interrogans serovar Bataviae and L Shermani. These results were similar to studies in domestic livestock and stray dogs in the Bangkok district. Among the elephants from Kanchanaburi there were significant associations between seropositivity and between the camp and between the prevalent serovars and the camp

Sreekumar, E., Janki, M.B., Arathy, D.S., Hariharan, R., Premraj, C.A., Rasool, T.J., 2007. Molecular characterization and expression of interferon-gamma of Asian elephant (Elephas maximus). Vet. Immunol. Immunopathol. 118, 75-83.
Abstract: Tuberculosis (TB) caused by Mycobacterial organisms has emerged as one of the major diseases in captive elephants. In vitro Interferon-gamma (IFN-gamma) assay is being used as an ancillary test for early detection of TB in domestic and captive wild animals. In the present study, basic sequence information and immunological cross-reactivity of this major cytokine of Asian elephants were explored. At predicted amino acid level, IFN-gamma of Asian elephant showed maximum identity to that of horse (73%). Other IFN-gamma amino acid sequences that showed high level identity were that of giant panda (72%), dog (71%), nine-banded armadillo (69%), cattle (63%) and human (62%). IFN-gamma promoter sequences of Asian elephant, human, cattle and mouse showed high level conservation of the putative transcription factor binding sites, TATA box and transcriptional start site. The functionally important human IFN-gamma promoter elements, such as AP-2IRE-BE, YY1-gammaIFN-BED, ATFCS and AP-1gammaINF binding sites, were absolutely conserved in the corresponding elephant sequence. There was only a single nucleotide variation in the other two important elements, NFAT-gammaINF and IFN-gammaPE, indicating the highly conserved regulation of IFN-gamma expression across different species. Phylogenetic analysis based on IFN-gamma protein sequences revealed a closer relation of Asian elephants and nine-banded armadillo. This shows a closer evolution of these members of Afrotheria and Xenarthra, respectively; and supports the previous reports based on mitochondrial DNA studies. In Western blot analysis, IFN-gamma of Asian elephant expressed in Escherichia coli was detected using an anti-bovine IFN-gamma monoclonal antibody, indicating immunological cross-reactivity

Une, Y., Mori, T., 2007. Tuberculosis as a zoonosis from a veterinary perspective. Comp Immunol Microbiol Infect Dis Aug 13; [Epub ahead of print].
Abstract: Tuberculosis is an important disease among many zoonoses, because both Mycobacterium tuberculosis and Mycobacterium bovis, which are the major causes of tuberculosis, are highly pathogenic, infect many animal species and thus are likely to be the source of infection in humans. In particular, monkeys are highly susceptible to these bacteria and are important spreaders. Recently, two outbreaks of M. tuberculosis occurred in four different kinds of monkeys and humans were also infected with the disease in Japan. In zoos, tuberculosis was reported not only in monkeys, but also in several different kinds of animals, including elephants. Pets such as dogs and cats are believed to be generally less susceptible to M. tuberculosis, but in this article we introduce a case of infection from man to dog by close contact. Japan is one of the few countries that have been able to control M. bovis infection. In other countries, however, cases of bovine tuberculosis and human M. bovis infection have been reported, and thus further attention is still required in the future.

Ball, R., Dumonceaux, G., Olsen, J., Burton, M.S., 2006. Comparison of trunk wash results matched to Multiantigen Print Immunoassay (MAPIA) in a group of captive Asian elephants (Elephas maximus). Proceedings International Elephant Conservation and Research Symposium 242-243.

Ball, R.L., Dumonceaux, G., Olsen, J.H., Burton, M.S., Lyashchenko, K. Comparison of trunk wash results matched to multiantigen print immunoassay (MAPIA) in a group of captive Asian elephants (Elephas maximus). 2006 Proceedings American Association of Zoo Veterinarians.  303-304. 2006.
Ref Type: Conference Proceeding
Abstract: Introduction: Between 1994 and June 2005, there were 34 confirmed cases of tuberculosis in elephants in the U.S. population. Thirty-one Asian (Elephas maximus) and three African (Loxodonta africana) elephants were affected. Mycobacterium tuberculosis was the etiologic agent in 33 cases and M. bovis in one case. Cases of tuberculosis caused by an unusual nontuberculous mycobacteria, M. szulgai have recently occurred as well.  Currently, TB in elephants remains a diagnostic dilemma. The sensitivity of trunk wash culture, the currently recommended test for diagnosis, is unknown. False negatives have been documented (trunk wash negative elephants that were subsequently found to be culture positive at necropsy).  Other non-culture techniques for TB diagnosis include ELISA, and PCR. A novel technology, MultiAntigen Print ImmunoAssay (MAPIA) and lateral-flow technology (Rapid Test)  has been evaluated and used to diagnose tuberculosis in captive elephants with encouraging results.  One concern with this serologic testing is the possibility of Mycobacterium other than tuberculosis (MOTT) cross-reacting with the antigen used in the Rapid Test or the MAPIA and leading to a false positive.  With numerous MOTT routinely cultured from trunk washes, this is a valid concern. Methods and Materials: A retrospective analysis was done at Busch Gardens Tampa Bay and Chembio, Inc. that matched trunk wash results to serum samples.  All serum was collected within 7 days of the trunk wash and analyzed with the Rapid Test and MAPIA. Four Asian elephants with a total of 18 samples met this criteria and had serum submitted for testing. Results and Discussion: Table 1 lists the results and the organisms cultured. While the sampling is limited in this pilot project, it appears that MOTT does not evoke a response when assayed with the Rapid Test or MAPIA. The recent cases of M. szulgai do demonstrate the potential usefulness for this test when a disease develops from MOTT.  The usefulness of this new technology, taken in conjunction with other clinical data including trunk washes when indicated, is a valuable tool in the healthcare of captive elephants.

LITERATURE CITED
1 Lacasse, C., K.C. Gamble, K. Terio, L.L. Farina, D.A. Travis, and M.Miller. 2005. Mycobacterium szulgai osteroarthritis and pneumonia in an African elephant (Loxdonta africana). Proc. Am. Assoc. Zoo Vet. Ann. Meet. Pp. 170-172.
2 Larsen, R.S., M.D. Salman, S.K. Mikota, R. Isaza, R.J. Montali, and J. Triantis.  2000.  Evaluation of a multiple-antigen enzyme-linked immunosorbent assay for detection of Mycobacterium tuberculosis infection in captive elephants.  J. Zoo Wildl. Med. 31:291-302.
3 Lyashchenko, K., et al.  2000. A multiantigen print immunoassay for the serological diagnosis of infectious diseases.  J. Immunol. Methods  242:91-100
4 Lyashchenko, K., M. Miller, and  W.R. Waters. 2005. Application of multiple antigen print immunoassay and rapid lateral flow technology for tuberculosis testing of elephants. Proc. Am. Assoc. Zoo Vet. Ann. Meet.  Pp. 64-65

Bojesen, A.M., Olsen, K.E., Bertelsen, M.F., 2006. Fatal enterocolitis in Asian elephants (Elephas maximus) caused by Clostridium difficile. Vet Microbiol Epub ahead of print.
Abstract: Two cases of fatal enteritis caused by Clostridium difficile in captive Asian elephants are reported from an outbreak affecting five females in the same zoo. Post mortem examination including histopathology demonstrated fibrinonecrotic enterocolitis. C. difficile was isolated by selective cultivation from two dead and a third severely affected elephant. Four isolates were obtained and found positive for toxin A and B by PCR. All isolates were positive in a toxigenic culture assay and toxin was demonstrated in the intestinal content from one of the fatal cases and in a surviving but severely affected elephant. PCR ribotyping demonstrated that the C. difficile isolates shared an identical profile, which was different from an epidemiologically unrelated strain, indicating that the outbreak was caused by the same C. difficile clone. It is speculated that the feeding of large quantities of broccoli, a rich source of sulforaphane, which has been shown to inhibit the growth of many intestinal microorganisms may have triggered a subsequent overgrowth by C. difficile. This is the first report of C. difficile as the main cause of fatal enterocolitis in elephants. The findings emphasize the need to regard this organism as potentially dangerous for elephants and caution is recommended concerning antibiotic treatment and feeding with diets containing antimicrobials, which may trigger an expansion of a C. difficile population in the gut.

Bojesen, A.M., Olsen, K.E., Bertelsen, M.F., 2006. Fatal enterocolitis in Asian elephants (Elephas maximus) caused by Clostridium difficile
456. Vet. Microbiol. 116, 329-335.
Abstract: Two cases of fatal enteritis caused by Clostridium difficile in captive Asian elephants are reported from an outbreak affecting five females in the same zoo. Post mortem examination including histopathology demonstrated fibrinonecrotic enterocolitis. C. difficile was isolated by selective cultivation from two dead and a third severely affected elephant. Four isolates were obtained and found positive for toxin A and B by PCR. All isolates were positive in a toxigenic culture assay and toxin was demonstrated in the intestinal content from one of the fatal cases and in a surviving but severely affected elephant. PCR ribotyping demonstrated that the C. difficile isolates shared an identical profile, which was different from an epidemiologically unrelated strain, indicating that the outbreak was caused by the same C. difficile clone. It is speculated that the feeding of large quantities of broccoli, a rich source of sulforaphane, which has been shown to inhibit the growth of many intestinal microorganisms may have triggered a subsequent overgrowth by C. difficile. This is the first report of C. difficile as the main cause of fatal enterocolitis in elephants. The findings emphasize the need to regard this organism as potentially dangerous for elephants and caution is recommended concerning antibiotic treatment and feeding with diets containing antimicrobials, which may trigger an expansion of a C. difficile population in the gut

Dumonceaux, G., Mikota, S., 2006. Tuberculosis treatment protocols and complications for elephants. Proceedings International Elephant Conservation and Research Symposium 84-85.

Helke, K.L., Mankowski, J.L., Manabe, Y.C., 2006. Animal models of cavitation in pulmonary tuberculosis
534. Tuberculosis. (Edinb. ) 86, 337-348.
Abstract: Transmission of tuberculosis occurs with the highest frequency from patients with extensive, cavitary, pulmonary disease and positive sputum smear microscopy. In animal models of tuberculosis, the development of caseous necrosis is an important prerequisite for the formation of cavities although the immunological triggers for liquefaction are unknown. We review the relative merits and the information gleaned from the available animal models of pulmonary cavitation. Understanding the host-pathogen interaction important to the formation of cavities may lead to new strategies to prevent cavitation and thereby, block transmission

Lutze-Wallace, C., Turcotte, C., 2006. Laboratory diagnosis of bovine tuberculosis in Canada for calendar year 2005
401. Canadian Veterinary Journal 47, 871-873.

Lyashchenko, K.P., Greenwald, R., Esfandiari, J., Olsen, J.H., Ball, R., Dumonceaux, G., Dunker, F., Buckley, C., Richard, M., Murray, S., Payeur, J.B., Andersen, P., Pollock, J.M., Mikota, S., Miller, M., Sofranko, D., Waters, W.R., 2006. Tuberculosis in elephants: antibody responses to defined antigens of Mycobacterium tuberculosis, potential for early diagnosis, and monitoring of treatment
438. Clin. Vaccine Immunol. 13, 722-732.
Abstract: 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

Michel, A.L., Bengis, R.G., Keet, D.F., Hofmeyr, M., de Klerk, L.M., Cross, P.C., Jolles, A.E., Cooper, D., Whyte, I.J., Buss, P., Godfroid, J., 2006. Wildlife tuberculosis in South African conservation areas:Implications and challenges. Veterinary Microbiology 112, 91-100.
Abstract: Tuberculosis, caused by Mycobacterium bovis, was first diagnosed in African buffalo in South Africa's Kruger National Park in 1990. Over the past 15 years the disease has spread northwards leaving only the most northern buffalo herds unaffected. Evidence suggests that 10 other small and large mammalian species, including large predators, are spillover hosts. Wildlife tuberculosis has also been diagnosed in several adjacent private game reserves and in the Hluhluwe-iMfolozi Park, the third largest game reserve in South Africa. The tuberculosis epidemic has a number of implications, for which the full effect of some might only be seen in the longterm. Potential negative long-term effects on the population dynamics of certain social animal species and the direct threat for the survival of endangered species pose particular problems for wildlife conservationists. On the other hand, the risk of spillover infection to neighboring communal cattle raises concerns about human health at the wildlife-livestock-human interface, not only along the western boundary of Kruger National Park, but also with regards to the joint development of the Greater Limpopo Transfrontier Conservation Area with Zimbabwe and Mozambique. From an economic point of view, wildlife tuberculosis has resulted in national and international trade restrictions for affected species. The lack of diagnostic tools for most species and the absence of an effective vaccine make it currently impossible to contain and control this disease within an infected free-ranging ecosystem. Veterinary researchers and policy-makers have recognized the need to intensify research on this disease and the need to develop tools for control, initially targeting buffalo and lion.

Mikota, S.K., Dumonceaux, G., Miller, M., Gairhe, K., Giri, K., Cheeran, J.V., Abraham, D., Lyashchenko, K., Larsen, S., Payeur, J., Waters, R., Kaufman, G., \, 2006. Tuberculosis in elephants: An update on diagnosis and treatment; implications for control in range countries. Proceedings International Elephant Conservation and Research Symposium 109-118.

Mikota, S.K., Miller, M., Dumonceaux, G., Giri, K., Gairhe, K., Hamilton, K., Paudel, S., Vincent, B. Elephant tuberculosis diagnosis: implications for elephant management in Asian range countries. 2006 Proceedings American Association of Zoo Veterinarians.  142-143. 2006.
Ref Type: Conference Proceeding
Abstract: Serologic tests including the ELISA, MAPIA (Multi-Antigen Print Immunoassay), and a rapid test, VetTB StatPak® (Chembio Diagnostic Systems, Inc., Medford, New York 11763 USA) have recently been developed and show great promise for the diagnosis of tuberculosis (TB) in elephants. These serologic tests detect antibodies to antigens of  Mycobacterium tuberculosis complex organisms and in some cases have detected infection years in advance of active disease and mycobacterial shedding. The diagnosis of active TB (by culture) or serologic conversion presents management challenges for captive elephants in Asian range countries.  Of the 2 billion humans world-wide infected with TB, fewer than 10% will develop active disease. This figure is unknown for elephants. The identification and management of infected elephants has ramifications for elephants and humans alike and issues such as public health and tourism may be impacted. TB is endemic among humans in Asia and where there is intermingling of elephants and humans, both species may act as reservoirs for disease transmission.  The various situations in which elephants are kept in Asia (government-owned, privately-owned, festivals, temples, zoos, etc.) make it difficult to develop a management strategy that will address all circumstances.  Other concerns are the cost of treatment for an elephant (~ $50,000 USD) and appropriate monitoring in resource-poor countries. The authors have recently undertaken the screening of 120 elephants in Nepal to further evaluate the above-mentioned (and other) diagnostic tests.  To our knowledge, this is the first organized, large-scale initiative to screen Asian elephants within a range country.  Preliminary discussions regarding the management of both culture and serologically positive government-owned and privately-owned elephants in Nepal have been initiated and may serve as a starting point for other countries as more elephants are screened within Asia.  Basic options for active (culturepositive) cases include (1) treatment, (2) segregation or (3) euthanasia.  Options for latent disease (culture-negative, serologically positive) cases include (1) treatment, (2) segregation and monitoring for active disease and (3) euthanasia.  The particular ownership/husbandry system, available resources and cultural constraints may dictate final management choices in range countries.

Moller, T., Roken, B.O., Lewerin, S.S., Lyashchenko, K., 2006. The elephant Rapid Test (RT) the future diagnostic test for TB (M. tuberculosis) in elephants? Call for a validation study in Europe. Proceedings International Elephant Conservation and Research Symposium 119-124.

Peloquin, C.A., Maslow, J.N., Mikota, S.K., Forrest, A., Dunker, F., Isaza, R., Peddie, L.R., Peddie, J., Zhu, M., 2006. Dose selection and pharmacokinetics of rifampin in elephants for the treatment of tuberculosis
385. J. Vet. Pharmacol. Ther. 29, 581-585.

Riley, L.W., 2006. Of mice, men, and elephants: Mycobacterium tuberculosis cell envelope lipids and pathogenesis
454. J. Clin. Invest 116, 1475-1478.
Abstract: Mycolic acids and structures attached to them constitute a major part of the protective envelope of Mycobacterium tuberculosis, and for this reason, their role in tuberculosis pathogenesis has been extensively studied. In this issue of the JCI, Rao et al. examine the effect of trans-cyclopropanation of oxygenated mycolic acids attached to trehalose dimycolate (TDM) on the murine immune response to infection (see the related article beginning on page 1660). Surprisingly, they found that an M. tuberculosis mutant lacking trans-cyclopropane rings was hypervirulent in mice. The recent recognition of a hypervirulence phenotype in mice associated with laboratory and clinical M. tuberculosis strains with altered cell wall components has provided new insights into how M. tuberculosis may establish persistent infection. However, to date, characterization of these bioactive products in pathogenesis has been largely reductionistic; the relationship of their effects observed in mice to the persistent infection and tuberculosis caused by M. tuberculosis observed in humans remains obscure

Rothschild, B.M., Martin, L.D., 2006. Did ice-age bovids spread tuberculosis? Naturwissenschaften 93, 565-569.
Abstract: Pathognomonic metacarpal undermining is a skeletal pathology that has been associated with Mycobacterium tuberculosis in bovids. Postcranial artiodactyl, perissodactyl, and carnivore skeletons were examined in major university and museum collections of North America and Europe for evidence of this and other pathology potentially attributable to tuberculosis. Among nonproboscidean mammals from pre-Holocene North America, bone lesions indicative of tuberculosis were restricted to immigrant bovids from Eurasia. No bone lesions compatible
with diagnosis of tuberculosis were found in large samples of other pre-Holocene (164 Oligocene, 397 Miocene, and 1,041 Plio-Pleistocene) North American mammals, including
114 antilocaprids. Given the unchanged frequency of bovid tubercular disease during the Pleistocene, it appears that most did not die from the disease but actually reached an
accommodation with it (as did the mastodon) (Rothschild and Laub 2006). Thus, they were sufficiently long-lived to assure greater spread of the disease. The relationships of the
proboscidean examples need further study, but present evidence suggests a Holarctic spread of tuberculosis during the Pleistocene, with bovids acting as vectors. While the role of other animals in the transmission of tuberculosis could be considered, the unique accommodation achieved by bovids and mastodons makes them the likely "culprits" in its spread.

Rothschild, B.M., Laub, R., 2006. Hyperdisease in the late Pleistocene:validation of an early 20th century hypothesis. Naturwissenschaften 93, 557-564.

Bertelsen, M.F., Bojesen, M., Olsen, K.E.P. Fatal enterocolitis in two Asian elephants (Elephas maximus) caused by Clostridium difficile. 2005 Proceedings AAZV, AAWV, AZA Nutrition Advisory Group.  66-67. 2005.
Ref Type: Conference Proceeding
Abstract: Altered behavior, anorexia and listlessness were observed in four of five adult captive female Asian elephants (Elephas maximus). Two animals recovered, while two died after 2 days. The dead elephants were subjected to post mortem examination including histopathology, demonstrating fibrinonecrotic enteritis and colitis. Clostridium difficile was isolated from both dead elephants and from the feces of the two surviving affected animals, and identified by selective cultivation and PCR identification. All isolates had the tcdA and tcdB toxin genes and were positive in a toxigenic culture assay. C. difficile toxin from the intestinal content of one of the fatal cases was demonstrated using cell-culture based cytotoxin assays. Clostridium perfringens type A and Clostridium septicum were also isolated from both dead animals. Although C. perfringens has been associated with ulcerative enteritis in an elephant,¹ in this case these isolates likely are incidental, as C. perfringens enterotoxin was not demonstrated, and as C. septicum is well known for producing rapid post mortem overgrowth.  Amplified fragment length polymorphism typing, showed that the C. difficile isolates recovered from the outbreak, all had the same fingerprint profile, indicating that all four elephants were affected by the same bacterial clone. These findings appear to be the first to demonstrate that C. difficile may cause enterocolitis in elephants. The results emphasize the need to regard this organism as potentially dangerous for elephants. Although there was no prior exposure to antibiotic agents in this case, caution is recommended when treating elephants with antibiotics, as this may trigger C. difficile induced enterocolitis in other species, most notably humans and horses.²
LITERATURE CITED
1 Bacciarini, L.N., O. Pagan, J. Frey, and A. Grone. 2001. Clostridium perfringens beta2-toxin in an African elephant (Loxodonta africana) with ulcerative enteritis. Vet. Rec. 149: 618-20.
2 Songer, J.G. 1996. Clostridial enteric diseases of domestic animals. Clin. Microbiol. Rev. 9: 216-234.

Cousins, D.V., Florisson, N., 2005. A review of tests available for use in the diagnosis of tuberculosis in non-bovine species. Rev. sci. tech. Off. int. Epiz. 24, 1039-1059.
Abstract: Bovine tuberculosis is an important disease that has impacts on regional and international trade. The disease can affect both social and economic stability and have a deleterious affect on species diversity. The intradermal tuberculin test has been in use for almost a century and, despite the technological advances of the last two decades, is still the only prescribed test for the
diagnosis of tuberculosis in cattle. Many other species of animal, including humans, can be infected with Mycobacterium bovis. This paper reviews the various tests that have been used by researchers for detecting infection with M. bovis in a variety of animal species, and attempts to prioritise or comment on the importance of having appropriately validated diagnostics for the different species. The difficulties of test validation using small numbers of animals, especially when tuberculosis occurs in only a few instances or the species of animal affected is rare and/or valuable, are discussed.

Lacasse, C., Gamble, K.C., Terio, K., Farina, L.L., Travis, D.A., Miller, M. Mycobacterium szulgai osteoarthritis and pneumonia in an African elephant (Loxodonta Africana). 2005 Proceedings AAZV, AAWV, AZA Nutrition Advisory Group.  170-172. 2005.
Ref Type: Conference Proceeding
Abstract: Tuberculosis, particularly Mycobacterium bovis and M. tuberculosis, is an important health issue in zoological collections.  Zoos are a particular public health concern because of the close contact between tuberculosis-susceptible animals and humans, specifically animal handlers and visitors.¹⁶ Evidence of M. tuberculosis transmission between humans and elephants, confirmed by DNA fingerprinting, has been reported.¹³ Between 1994 and 2001, M. tuberculosis was isolated from trunk washes of captive elephants from 11 herds in the United States.¹⁷  To date, most reported cases of tuberculosis have occurred in captive Asian elephants (Elephas maximus).¹⁴ In 1997, the National Tuberculosis Working Group for Zoo and Wildlife Species partnered with the USDA to formulate the "Guidelines for the Control of Tuberculosis in Elephants." ¹⁵ This document outlines criteria for the testing, surveillance, and treatment of tuberculosis in elephants. The guidelines recommend annual monitoring of elephants by mycobacterial culture of three direct trunk washes collected over 1 wk.  Isolation of Mycobacterium avium and non-tuberculous mycobacteria from elephant trunk wash samples is common, but these organisms have not been associated with clinical disease.^14,18 This case report details clinical disease with fatal complications of an atypical mycobacterial infection in an African elephant (Loxodonta africana). In September 2003, an African elephant presented with acute, severe lameness of the left rear limb with subsequent swelling of the stifle.  Diagnostic procedures included aspiration cytology of the swelling, radiographs, and thermographic imaging.  The exact location of the injury could not be detected, but a lesion to the stifle or coxofemoral articulation was suspected.  After 13 mo of treatment, including pulse therapy with a variety of nonsteroidal anti-inflammatory drugs (NSAIDs), weekly to biweekly injections of polysulfated glycosaminoglycan, and intensive foot care efforts to treat secondary pedal lesions of both rearlimbs, the animal died acutely.  Gross necropsy revealed granulomatous osteomyelitis with necrosis/loss of the femoral head and acetabulum and pulmonary granulomas.  Both of these lesions contained acid-fast bacteria on cytology. While awaiting confirmatory culture results, quarantine procedures were established for the elephant facility and a program was established to screen all zoo personnel in close contact with the elephant or who participated in the necropsy.  All personnel were tested by the Chicago Department of Public Health without documented conversion. Mycobacterium szulgai was ultimately cultured from both coxofemoral and pulmonary lesions. Mycobacterium szulgai is an uncommon nontuberculous mycobacterium that is usually isolated from pathologic lesions in humans.²¹ This bacterial species was first identified in 1972.¹¹ The lungs are the main locality for pathologic manifestation in humans and several cases have been in patients with acquired immunodeficiency syndrome.^9,20,21 Infection due to M. szulgai most frequently produces thin-walled cavities in lungs resembling tuberculosis.⁴ Other documented sites of infection include the skin, bone, and tendon sheath (causing a carpal tunnel syndrome).^{2,9,10,12,19,20}  Intra-operative contamination from ice water has led to M. szulgai keratitis after laser-assisted ophthalmic surgeries^.6 A case of disseminated disease in a previously healthy young human has been reported.⁵  No evidence of human-to-human transmission of this organism has been documented and human cases are believed to originate from environmental sources.¹²  The natural habitat of the organism is unknown, but previous reports suggest an association of the bacteria with water of swimming pools and fish tanks.^1,21 The organism has been cultured from a snail and tropical fish.^1,3 No standard recommendation for the treatment of M. szulgai infection currently exists.  In general, triple antibiotic therapies used in standard mycobacterial treatments are reported with a low rate of relapses and sterilization of sputum cultures within a mean of 3 mo.³ Pulmonary lesions in this elephant were chronic; it was not possible to determine when initial infection occurred. Infection could have occurred in captivity or in the wild prior to captivity. Three trunk washes over the past year had been negative for mycobacterial culture. Osteomyelitis in the hip may have developed secondary to hematogenous spread from the lungs with the acute lameness resulting from a pathologic fracture associated with this infection. Alternatively, though considered less likely, a traumatic fracture of the hip could have occurred, with bacterial inoculation and secondary osteomyelitis as a result of increased blood flow to the site. The source of infection for this elephant remains unknown.  Prevalence of this organism in the natural habitat or captive environment of the elephants has not been previously documented.
LITERATURE CITED
1 Abalain-Colloc, M.L., D. Guillerm, M. Salaun, S. Gouriou, V. Vincent, and B. Picard.  2003.  Mycobacterium szulgai isolated from a patient, a tropical fish, and aquarium water.  Eur. J. Clin. Microbiol. Infect. Dis.  22: 768-769.
2.Cross, G.M., M. Guill, and J.K. Aton.  1985.  Cutaneous Mycobacterium szulgai infection. Arch. Dermatol. 121: 247-249.
3. Davidson, P.T. 1976. Mycobacterium szulgai: a new pathogen causing infection of the lung.  Chest 69: 799- 801.
4. Dylewski, J.S., H.M. Zackon, A.H. Latour, and G.R. Berry.  1987.  Mycobacterium szulgai: an unusual pathogen.  Rev. Infect. Dis.  9: 578-580.
5. Gur, H., S. Porat, H. Haas, Y. Naparstek, and M. Eliakim.  1984.  Disseminated mycobacterial disease caused by Mycobacterium szulgai. Arch. Intern. Med. 144: 1861-1863.
6.Holmes, G.P., G. Bond, R.C. Fader, and S.F. Fulcher.  2002. A cluster of cases of Mycobacterium szulgai keratitis that occurred after laser-assisted in situ keratomileusis.  Clin. Infect. Dis. 34: 1039-1046.
7.Horusitzky, A., X. Puechal, D. Dumont, T. Begue, M. Robineau, and M. Boissier.  2000.  Carpal tunnel syndrome caused by Mycobacterium szulgai. J. Rheumatol 27: 1299-1302.
8.Hurr, H., and T. Sorg.  1998.  Mycobacterium szulgai osteomyelitis.  J. Infect.  37: 191-192.
9.Luque, A.E., D. Kaminski, R. Reichman, and D. Hardy. 1998.  Mycobacterium szulgai osteomyelitis in an AIDS patient. Scand. J. Infect. Dis. 30: 88-91.
10.Maloney, J.M., C.R. Gregg, D.S. Stephens, F.A. Manian, and D. Rimland.  1987.  Infections caused by Mycobacterium szulgai in humans.  Rev. Infect. Dis.  9: 1120-1126.
11.Marks, J., P.A. Jenkins, and M. Tsukamura.  1972.  Mycobacterium szulgai: a new pathogen.  Tubercle 53: 210.
12.Merlet, C., S. Aberrane, F. Chilot, and J. Laroche.  2000.  Carpal tunnel syndrome complicating hand flexor tenosynovitis due to Mycobacterium szulgai. Joint Bone Spine 67: 247-248.
13.Michalak, K., C. Austin, S. Diesel, J.M. Bacon, P. Zimmerman, and J. N. Maslow.  1998. Mycobacterium tuberculosis infection as a zoonotic disease: transmission between humans and elephants. Emerg. Infect. Dis. 4: 283-287.
14.Mikota, S.K., R.S. Larsen, and R.J. Montali.  2000.  Tuberculosis in elephants in North America.  Zoo Biol. 19: 393-403.
15.National Tuberculosis Working Group for Zoo and Wildlife Species. 2000. Guidelines for the control of tuberculosis in elephants.  USDA Animal and Plant Health Inspection Services.
16.Oh, P., R. Granich, J. Scott, B. Sun, M. Joseph, C. Stringfield, S. Thisdell, J. Staley, D. Workman-Malcolm, L. Borenstein, E. Lehnkering, P. Ryan, J. Soukup, A. Nitta, and J. Flood.  2002.  Human exposure following  Mycobacterium tuberculosis infection of multiple animal species in a metropolitan zoo.  Emerg. Infect. Dis. 8: 1290-1293.
17.Payeur, J.B., J.L. Jarnagin, J.G. Marquardt, and D.L. Whipple.  2002.  Mycobacterial isolations in captive elephants in the United States.  Ann. N.Y. Acad. Sci. 969: 256-258.
18.Shojaei, H., J.G. Magee, R. Freeman, M. Yates, N.U. Horadagoda, and M. Goodfellow.  2000. Mycobacterium elephantis sp. nov., a rapidly growing non-chromogenic Mycobacterium isolated from an elephant.  Int. J. Syst. Evol. Microbiol.  50: 1817-1820.
19.Stratton, C.W., D.B. Phelps, and L.B. Reller.  1978.  Tuberculoid tenosynovitis and carpal tunnel syndrome caused by Mycobacterium szulgai.  Am. J. Med.  65: 349-351.
20.Tappe, D., P. Langmann, M. Zilly, H. Klinker, B. Schmausser, and M. Frosch.  2004.  Osteomyelitis and skin ulcers caused by Mycobacterium szulgai in an AIDS patient.  Scand. J. Infect. Dis. 36: 883-885.
21.Tortoli, E., G. Besozzi, C. Lacchini, V. Penati, M.T. Simonetti, and S. Emler.  1998.  Pulmonary infection due to Mycobacterium szulgai, case report and review of the literature.  Eur. Respir. J.  11: 975-977.

Larsen, R.S., Kay, M., Triantis, J., Salman, M.D. Update on serological detection of Mycobacterium tuberculosis infection in Asian elephants. 2005 Proceedings AAZV, AAWV, AZA Nutrition Advisory Group.  62-63. 2005.
Ref Type: Conference Proceeding
Abstract: Tuberculosis has become an important disease in captive elephants, particularly Asian elephants (Elephas maximus). Diagnosing tuberculosis in elephants has been problematic as many tests have inadequate sensitivity or specificity.2-4 A multiple-antigen enzyme-linked immunosorbent assay (ELISA) was previously investigated for detecting infection in Asian elephants and African elephants (Loxodonta africana); this test had excellent sensitivity and specificity, but needed further evaluation.1 Modifications to the multiple-antigen ELISA panel have since been made. Valuable antigens were retained, other antigens were removed, and new ones were added.  This modified ELISA was re-evaluated, using serum from 68 Asian elephants. Sixteen had M. tuberculosis -positive trunk cultures, while 52 were either culture negative at necropsy or had a history of negative trunk cultures and no contact with infected elephants. Seven elephants were evaluated over time. The test was 100% (95% CI; 95-100%) specific and 94% (95% CI; 79-100%) sensitive using two of the six antigens (M. bovis strain AN5 culture filtrate and M. tuberculosis early secretory antigenic target 6). "Effectively-treated" elephants had decreasing seroreactivity, but those that were culture-positive post-treatment were more consistently seroreactive.  Although "effectivelytreated" elephants had declining seroreactivity, they still usually had higher values than animals that had never been infected. Serology continues to show great promise in detecting tuberculosis in elephants, often detecting infection months-to-years sooner than trunk wash culture.  Advances in techniques may soon make serology even more practical.  While serology should not replace trunk-wash culture, it is a useful adjunct for early detection of infection in elephants and for monitoring treatment.
ACKNOLWEDGMENTS We thank the many veterinarians, owners, caretakers, and managers of elephant-owning institutions that participated in this investigation, as well as Drs. Michele Miller and Susan Mikota for helping to coordinate sample collection. We also thank Kimberly Deines and other laboratory personnel who processed ELISA samples.  The study was partially funded by a grant from USDA, CSREES to Colorado State University Program of Economically Important Infectious Animal Diseases.
LITERATURE CITED
1.Larsen, R.S., M.D. Salman, S.K. Mikota, R. Isaza, R.J. Montali, and J. Triantis. 2000.  Evaluation of a multiple-antigen enzyme-linked immunosorbent assay for detection of Mycobacterium tuberculosis in captive elephants.  J. Zoo Wildl. Med. 31: 291-302.
2. Mikota, S.K., L. Peddie, J. Peddie, R. Isaza, F. Dunker, G. West, W. Lindsay, R.S. Larsen, M.D. Salman, D. Chatterjee, J. Payeur, D. Whipple, C. Thoen, D.S. Davis, R.J. Montali and J. Maslow.  2001. Epidemiology and diagnosis of Mycobacterium tuberculosis in six groups of elephants.  J. Zoo Wildl. Med. 32: 1-16.
3. Mikota, S.K., R.S. Larsen, and R.J. Montali.  2000.  Tuberculosis in elephants in North America.  Zoo Biol. 19: 393-403.
4. U.S. Department of Agriculture.  2003.  Guidelines for the control of tuberculosis in elephants.  Animal and Plant Health Inspection Service; Animal Care. Washington, D.C. http://www.aphis.usda.gov/ac/TBGuidelines2003.pdf.

Lewerin, S.S., Olsson, S.L., Eld, K., Roken, B., Ghebremichael, S., Koivula, T., Kallenius, G., Bolske, G., 2005. Outbreak of Mycobacterium tuberculosis infection among captive Asian elephants in a Swedish zoo
637. Veterinary Record 156, 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

Lyashchenko, K., Miller, M., Waters, W.R. Application of MAPIA (Multiple antigen print immunoassay) and rapid lateral flow technology for tuberculosis testing of elephants. 2005 Proceedings AAZV, AAWV, AZA Nutrition Advisory Group.  64-65. 2005.
Ref Type: Conference Proceeding
Abstract: Tuberculosis (TB) remains a serious re-emerging disease in wildlife and zoo animals. Mycobacterium tuberculosis has been isolated from 30 captive Asian elephant (Elephas maximus within 14 herds in the United States (1994-2004) and Mycobacterium bovis has been isolated from one African elephant (Loxodonta africana) (Mikota, pers. comm.).3 There are several challenges with elephant TB diagnosis. Culture of trunk wash has relatively poor sensitivity and is subject to contamination.  Skin test is not validated in elephants and there is little reliability in these results.4   Serologic tests are appealing because  samples can be stored for future analysis, archived samples can be analyzed, various assay platforms can be directly compared, and these assays are amenable to serial analysis (e.g., to monitor therapy).  There is currently a multiple antigen ELISA test available for experimental use in elephants.1

To improve tuberculosis control, new diagnostic tools should be rapid, accurate, and host species-independent. Two novel serologic methods, MultiAntigen Print ImmunoAssay (MAPIA) and lateral-flow technology (Rapid Test), have been adapted for use in white-tailed deer, European badger, cattle, and Asian and African elephants for the detection of TB-specific antibody. Serologic markers of diagnostic importance have been identified for each host tested so far. With MAPIA, a machine prints specific antigens horizontally on a nitrocellulose membrane which can be cut into strips and used in Western blot.2   Strips are incubated with test serum samples, then an anti-Ig conjugate and color developer.  Using this assay, an antibody response to multiple mycobacterial antigens has been observed in sera from M. tb-infected elephants. No antibody response was detected to any antigens in non-infected elephant sera.  Additionally, the kinetics of antibody responses by elephants undergoing antibiotic therapy indicates that the MAPIA could be used for monitoring treatment and to determine recrudescence of infection. 

Using selected antigens, a lateral-flow test was developed for rapid antibody detection that can be used in multiple species. The Rapid Test can use serum, plasma, or whole blood and provides results within 15 min.  These tests are similar to in-clinic tests for FIV/FeLV detection (snap test, IDDEX). If a band is present in the test strip, it indicates a positive reaction (antibody present).
A panel of sera from healthy and TB infected elephants showed good correlation between the MAPIA and the rapid test (Table 1).

In summary, it appears that TB-infected elephants produce a robust antibody response that can be detected in serologic assays.  Of special significance is the kinetics of the response, which may permit earlier detection of infection than current diagnostic methods.  While initial results are promising, additional studies are required to validate these two assays.  A relatively small set of serum samples from documented infected and non-infected elephants was used, and more samples are needed to further validate the tests. MAPIA has been used to optimize antigen selection in order to make the most sensitive and specific Rapid Test. This strategy may also allow for identification of "treatment-sensitive" antigens that could be used in the MAPIA format to monitor TB therapy.  While elephants will be used as an initial "proof of concept" species for test development, additional samples from other species will also be evaluated to determine applicability to other species (i.e., a host species-independent test), thus benefiting other groups such as primates, rhinos, cervids, etc.

ACKNOWLEDGMENTS
The authors thank the zoos and individuals that have provided samples and assistance with this research, including Ray Ball, Carol Buckley, Jenifer Chatfield, Genny Dumonceaux, Javan Esfandiary, Rena Greenwald, Scott Larsen, Susan Mikota, Torsten Moller, Dick Montali, Mike Richards, Heidi Riddle, Mo Salman, Scott Terrell, and many others.  This research was supported by Chembio Diagnostics, Inc.
LITERATURE CITED
1 Larsen, R.S., M.D. Salman, S.K. Mikota, R. Isaza, R.J. Montali, and J. Triantis. 2000.  Evaluation of a multiple-antigen enzyme-linked immunosorbent assay for detection of Mycobacterium tuberculosis  
  infection in captive elephants.  J. Zoo Wildl. Med. 31:291-302.
2 Lyashchenko, K., et al.  2000. A multiantigen print immunoassay for the serological diagnosis of infectious diseases.  J. Immunol. Methods  242:91-100. 
3 Mikota, S.K., and J. Maslow.  2002.  Epidemiology and treatment of tuberculosis in elephants:  2002.  Proc. Am. Assoc. Zoo Vet. Annu. Meet.  Pp. 384-387.

Maslow, J.N., Mikota, S.K., Zhu, M., Isaza, R., Peddie, L.R., Dunker, F., Peddie, J., Riddle, H., Peloquin, C.A., 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, 21-27.
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

Maslow, J.N., Mikota, S.K., Zhu, M., Riddle, H., Peloquin, C.A., 2005. Pharmacokinetics of ethambutol (EMB) in elephants. J Vet Pharmacol Ther 28, 321-323.

Maslow, J.N., Mikota, S.K., Zhu, M., Isaza, R., Peddie, L.R., Dunker, F., Peddie, J., Riddle, H., 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, 1-7.
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. jol.maslow@med.va.gov

Moller, T., Roken, B., Petersson, L., Vitaud, C., Lyashchenko, K. Preliminary results of a new serological test for detection of TB-infection (Mycobacterium tuberculosis) in elephants (Elephas maximus and Loxodonta africanum) - Swedish Case studies. Verh.ber.Erkrg.Zootiere. 42, 173-181. 2005.
Ref Type: Conference Proceeding

Naz, R.K., Gupta, S.K., Gupta, J.C., Vyas, H.K., Talwar, A.G., 2005. Recent advances in contraceptive vaccine development: a mini-review
577. Hum. Reprod. 20, 3271-3283.
Abstract: Contraceptive vaccines (CV) may provide viable and valuable alternatives to the presently available methods of contraception. The molecules that are being explored for CV development either target gamete production [luteinizing hormone-releasing hormone (LHRH)/GnRH, FSH], gamete function [sperm antigens and oocyte zona pellucida (ZP)], and gamete outcome (HCG). CV targeting gamete production have shown varied degrees of efficacy; however, they either affect sex steroids causing impotency and/or show only a partial rather than a complete effect in inhibiting gametogenesis. However, vaccines based on LHRH/GnRH are being developed by several pharmaceutical companies as substitutes for castration of domestic pets, farm and wild animals, and for therapeutic anticancer purposes such as in prostatic hypertrophy and carcinoma. These vaccines may also find applications in clinical situations that require the inhibition of increased secretions of sex steroids, such as in uterine fibroids, polycystic ovary syndrome, endometriosis and precocious puberty. CV targeting molecules involved in gamete function such as sperm antigens and ZP proteins are exciting choices. Sperm constitute the most promising and exciting target for CV. Several sperm-specific antigens have been delineated in several laboratories and are being actively explored for CV development. Studies are focused on delineating appropriate sperm-specific epitopes, and increasing the immunogenicity (specifically in the local genital tract) and efficacy on the vaccines. Anti-sperm antibody (ASA)-mediated immunoinfertility provides a naturally occurring model to indicate how a vaccine might work in humans. Vaccines based on ZP proteins are quite efficacious in producing contraceptive effects, but may induce oophoritis, affecting sex steroids. They are being successfully tested to control feral populations of dogs, deer, horses and elephants, and populations of several species of zoo animals. The current research for human applicability is focused on delineating infertility-related epitopes (B-cell epitopes) from oophoritis-inducing epitopes (T-cell epitopes). Vaccines targeting gamete outcome primarily focus on the HCG molecule. The HCG vaccine is the first vaccine to undergo Phase I and II clinical trials in humans. Both efficacy and lack of immunopathology have been reasonably well demonstrated for this vaccine. At the present time, studies are focused on increasing the immunogenicity and efficacy of the birth control vaccine, and examining its clinical applications in various HCG-producing cancers. The present article will focus on the current status of the anti-sperm, anti-ZP, anti-LHRH/GnRH and anti-HCG vaccines

Neil, K.M., Caron, J.P., Orth, M.W., 2005. The role of glucosamine and chondroitin sulfate in treatment for and prevention of osteoarthritis in animals. Journal of the American Veterinary Medical Association 226, 1079-1088.

Pandey, R., Khuller, G.K., 2005. Antitubercular inhaled therapy: opportunities, progress and challenges. Journal of Antimicrobial Therapy 55, 430-435.

Sanchez, C.R., Murray, S.Z., Isaza, R., Papich, M.G., 2005. Pharmacokinetics of a single dose of enrofloxacin administered orally to captive Asian elephants (Elephas maximus). Am J Vet Res 66, 1948-1953.
Abstract: OBJECTIVE: To determine the pharmacokinetics of enrofloxacin after oral administration to captive elephants. ANIMALS: 6 clinically normal adult Asian elephants (Elephas maximus). PROCEDURE: Each elephant received a single dose of enrofloxacin (2.5 mg/kg, PO). Three elephants received their complete diet (pellets and grain) within 2 hours after enrofloxacin administration, whereas the other 3 elephants received only hay within 6 hours after enrofloxacin administration. Serum concentrations of enrofloxacin and ciprofloxacin were measured by use of high-performance liquid chromatography. RESULTS: Harmonic mean half-life after oral administration was 18.4 hours for all elephants. Mean +/- SD peak serum concentration of enrofloxacin was 1.31 +/- 0.40 microg/mL at 5.0 +/- 4.2 hours after administration. Mean area under the curve was 20.72 +/- 4.25 (microg x h)/mL. CONCLUSIONS AND CLINICAL RELEVANCE: Oral administration of enrofloxacin to Asian elephants has a prolonged elimination half-life, compared with the elimination half-life for adult horses. In addition, potentially therapeutic concentrations in elephants were obtained when enrofloxacin was administered orally at a dosage of 2.5 mg/kg. Analysis of these results suggests that enrofloxacin administered with feed in the manner described in this study could be a potentially useful antimicrobial for use in treatment of captive Asian elephants with infections attributable to organisms, such as Bordetella spp, Escherichia coli, Mycoplasma spp, Pasteurella spp, Haemophilus spp, Salmonella spp, and Staphylococcus spp.

Waters, W.R., Palmer, M.V., Bannantine, J.P., Greenwald, R., Esfandiari, J., Andersen, P., McNair, J., Pollock, J.M., Lyashchenko, K.P., 2005. Antibody responses in reindeer (Rangifer tarandus) infected with Mycobacterium bovis. Clinical and Diagnostic Laboratory Immunology 12, 727-735.
Abstract: Despite having a very low incidence of disease, reindeer (Rangifer tarandus) are subject to tuberculosis (TB) testing requirements for interstate shipment and herd accreditation in the United States. Improved TB tests are desperately needed, as many reindeer are falsely classified as reactors by current testing procedures. Sera collected sequentially from 11 (experimentally) Mycobacterium bovis-infected reindeer and 4 noninfected reindeer were evaluated by enzyme-linked immunosorbent assay (ELISA), immunoblotting, and multiantigen print immunoassay (MAPIA) for antibody specific to M. bovis antigens. Specific antibody was detected as early as 4 weeks after challenge with M. bovis. By MAPIA, sera were tested with 12 native and recombinant antigens, which were used to coat nitrocellulose. All M. bovis-infected reindeer developed responses to MPB83 and a fusion protein, Acr1/MPB83, and 9/11 had responses to MPB70. Other antigens less commonly recognized included MPB59, ESAT-6, and CFP10. Administration of purified protein derivatives for skin testing boosted serum antibody responses, as detected by each of the assays. Of the noninfected reindeer, 2/4 had responses that were detectable immediately following skin testing, which correlated with pathological findings (i.e., presence of granulomatous lesions yet the absence of acid-fast bacteria). The levels of specific antibody produced by infected reindeer appeared to be associated with disease progression but not with cell-mediated immunity. These findings indicate that M. bovis infection of reindeer elicits an antibody response to multiple antigens that can be boosted by skin testing. Serological tests using carefully selected specific antigens have potential for early detection of infections in reindeer.

Zhu, M., Maslow, J.N., Mikota, S.K., Isaza, R., Dunker, F., Riddle, H., Peloquin, C.A., 2005. Population pharmacokinetics of pyrazinamide in elephants
564. J. Vet. Pharmacol. Ther. 28, 403-409.
Abstract: 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

Hirsch, D.C., Biberstein, E.L., 2004. Mycobacterium. In: Hirsch, D.C., MacLachlan, N.J., Walker, R.L. (Eds.), Veterinary Microbiology. Blackwell, Ames, Iowa, pp. 223-234.

Janssen, D.L., Oosterhuis, J.E., Fuller, J., Williams, K. Field technique: A method for obtaining trunk wash mycobacterial cultures in anesthetized free-ranging African elephants (Loxodonta africana). 2004 PROCEEDINGS AAZV, AAWV, WDA JOINT CONFERENCE.  582-583. 2004.
Ref Type: Conference Proceeding
Abstract: The Guidelines for the Control of Tuberculosis in Elephants 2003 (Guidelines) of the National tuberculosis Working Group for Zoo and Wildlife Species were written to protect the health and safety of captive elephants together with their handlers and the viewing public.1 The Guidelines specifically address the display and transport of captive elephants but do not address the unique situation of free-living elephants being imported and subsequently displayed to the public.

Although the Guidelines describe a technique for collecting and handling a trunk wash in a trained, standing, non-anesthetized elephant, it does not describe a similar technique for anesthetized elephants in lateral recumbency. In an attempt to detect active mycobacterial infection in a group of 3 male and 8 female free-ranging African elephants scheduled for import into the United States, a technique was developed for collecting trunk washes in recumbent,  anesthetized elephants for mycobacterial culture.

A South African game-capture crew, experienced in translocating elephants, anesthetized elephants in groups via remote drug delivery and from a helicopter. The ground crew accomplished multiple simultaneous procedures including anesthesia maintenance and monitoring, physical and reproductive examinations, collection of general diagnostic and investigative samples, and trunk washes for mycobacterial cultures. This was accomplished while the capture crew was preparing animals for loading into specially designed trailers for transport to a holding boma. Little time was available for any one of procedure with multiple
animals being attended to at one time.

Once an elephant was stable in lateral recumbency, a 3-m foal stomach tube, prepackaged and sterilized, was inserted into the dependent side of the trunk tip. It was then gently fed up the trunk approximately 2.5 m. A 50-ml sample suction trap was attached to the end of the foal tube.The suction trap was then attached to a battery powered, portable aspirator pump designed for emergency medical care. The aspiration pump was activated to collect secretions from the most proximal portion of the trunk. If little or no secretions were collected by this means, the system was disconnected between the sample trap and the foal tube. Then, 100 ml of sterile saline was placed into raised end of the foal tube allowing it to drain toward the tip through gravity. The suction trap and aspiration pump were reattached to collect a sample in the sample trap. Then, the sample trap was replaced with a new trap, and the foal tube was inserted into the oral pharynx for collection of a separate oropharyngeal sample. This same procedure was repeated
with each elephant.

ACKNOWLEDGMENTS
So African veterinarians, Mike Bester, Larry Killmar, Janet Payeur, ARC/OVI, Thomas Hildebrant, Eric Zeehandelar, Kevin Reily, Denise SoFranko.

LITERATURE CITED
1. National tuberculosis Working Group for Zoo and Wildlife Species. 2003. Guidelines for the Control of Tuberculosis in Elephants 2003. USDA-APHIS: http://www.aphis.usda.gov/ac/TBGuidelines2003.pdf

Stringfield, C.E., Oh, P., Granich, R., Scott, J., Sun, B., Joseph, M., Flood, J., Sedgwick, C.J. Epidemiologic investigation of a Mycobacterium tuberculosis infection of multiple animal species in a metropolitan zoo. 2004 PROCEEDINGS AAZV, AAWV, WDA JOINT CONFERENCE.  46-48. 2004.
Ref Type: Conference Proceeding
Abstract: From 1997 to 2000, six cases of Mycobacterium tuberculosis (TB) infection were diagnosed in three species of animals at, or recently originating from, the Los Angeles Zoo. Restriction fragment length polymorphism (RFLP) analysis showed that five of six animal isolates shared an identical IS6110 pattern, with the sixth differing only by one additional band. A multiinstitutional epidemiologic investigation was conducted to identify and interrupt possible transmission among the animal cases, and to screen personnel for active TB infection and TB skin-test conversion.
Animal Cases
In April and October of 1994, Asian elephant (Elephas maximus) #1 and Asian elephant #2 arrived at the Los Angeles Zoo from a private elephant facility where they had lived together. They were housed together at the zoo until November of 1996 when elephant #2 was returned to the facility for several months before transfer to another zoo. In the spring of 1997, Elephant #1 (30 yr old) died of salmonellosis, with M. tuberculosis found in granulomatous lymph node lesions from the thoracic and abdominal cavities, and Elephant #2 (30 yr old) was found to have a positive trunk wash culture for M. tuberculosis. In July of 1998, one of a closed herd of three Rocky Mountain goats (Oreamnos americanus) consisting of a sire and two offspring, died of pulmonary M. tuberculosis at 6 yr of age. The goat's asymptomatic herdmates were screened and had negative chest radiographs and tracheal wash cultures, but one of the two goats was positive on tuberculin skin-test. In October of 1998, a clinically normal Black rhinocerus (Diceros bicornis) was diagnosed with Mycobacerium tuberculosis after a positive skin test and nasal wash culture. In the winter of 1998, the two remaining goats were evaluated again with negative chest radiographs and tracheal wash cultures. However, 1 yr later, both were humanely euthanatized at 8 and 12 yr of age due to clinical evidence of tuberculosis on chest radiographs (both animals), and active clinical signs in one (neither were able to be orally treated). In January of 2001, a rhino was humanely euthanatized after a protracted illness that was nonresponsive to aggressive treatment. The rhino was found to have severe multifocal hemosiderosis and atypical mycobacterial infection in her lungs, with no M. tuberculosis  cultured. This animal had been treated with oral Isoniazid and Rifampin for 1 yr, cultured routinely, and was never culture positive again.
 Epidemiologic Investigation
Investigators examined medical and location histories of the affected animals, animal handling practices, health-care procedures, and performed an infection control assessment of the animal compounds and health-care facilities (including measuring air flow in the compounds by smoke testing). We conducted a review of zoo employee medical records for evidence of TB symptoms, tuberculin skin-test results, and chest radiograph information. A list of current and former employees was cross-matched with reported TB cases in the California state registry from 1985 to 2000. As part of the annual occupational health screening in June of 2000, zoo employees underwent questioning regarding TB symptoms, received tuberculin skin tests, and completed a questionnaire on medical history, job type, and history of contact with the infected animals.
Epidemiologic Findings
No common cross-species contact outside the animal compounds and no contact with an infectious human were found. The distance at which the public was kept from the animals and the distance of the compounds from each other (the elephant compound was 27 meters from the rhino compound and the goat compound was 90 m from both) suggests that direct transmission was unlikely. No active TB cases in humans were found, and no matches were found in the database of reporte d cases. The RFLP analysis of this strain of M. tuberculosis matched that of three elephants with which #1 and #2 were housed at a private elephant facility from September of 1993-February of 1994.1 We hypothesize that elephants #1 and #2 were infected at the private facility and were shipped with latent M. tuberculosis infection in 1994, subsequently infecting the black rhino and Mountain goats at the Los Angeles Zoo.
Of interest, animal caretaking and animal contact were not associated with a positive tuberculin skin-test, while groundskeepers were found to have an increased risk of tuberculin skin-test conversion compared with other job categories. Employees attending the elephant necropsy and employees who trained elephants were more likely to have tuberculin skin-test conversion than those who did not.
Conclusion
This is the first documented human and veterinary epidemiologic investigation of Mycobacterium tuberculosis affecting multiple species in a zoo. ² No evidence of transmission from humans to animals or active infections in humans were found. Genotyping evidence strongly suggests transmission from one species to another, although no evidence of transmission was discovered. Human tuberculin skin-test conversions associated with the elephants were most likely due to lack of respiratory protection for these employees when the risk of TB infection was not known. The finding that groundskeepers and not animal handlers were associated with a higher risk of tuberculin skin-test conversion was surprising, and we hypothesized that this may have to do with groundskeepers as a group being more likely to have
been born outside of the United States.
Control measures to eliminate the spread of disease to people and animals were undertaken immediately and throughout this outbreak, and no further cases of M. tuberculosis have been diagnosed at the zoo in the past 3 yr despite ongoing surveillance. Four elephants and three rhinos that had direct contact with the infected animals remain TB negative by trunk and nasal wash culture methods as outlined by the USDA for elephant TB surveillance. Methods of indirect transmission in mammalian zoo species and causes of variability in infection and morbidity within and among species warrant further investigation. Ongoing vigilance, occupational health programs and infection control measures in potentially exposed animals are recommended to prevent ongoing transmission of M. tuberculosis in zoo settings.
Acknowledgments
The authors thank the Animal Care and Animal Health staff of the Los Angeles Zoo who cared so well for these animals, and the veterinarians (including consulting pathologists), technicians, and medical records staff who collected, analyzed, and organized the clinical data. We could not have performed this evaluation without Sue Thisdell, Safety Officer at the Los Angeles Zoo; Jothan Staley and Donna Workman-Malcom of the City of Los Angeles Occupational Health Services Division; Lee Borenstein, Elenor Lehnkering, Patrick Ryan, Jeanne Soukup, and Annette Nita of the Los Angeles County Department of Health Services; and Diana Whipple for her RFLP expertise.
LITERATURE CITED
1. Mikota, S.K., L. Peddie, J. Peddie, R. Isaza, F. Dunker, G. West, W. Lindsay, R.S.Larsen, M. D. Salman, D. Chatterjee, J. Payeur, D. Whipple, C. Thoen, D. Davis, C. Sedgwick, R.J. Montali, M. Ziccardi, J. Maslow. 2001. Epidemiology and diagnosis of Mycobacterium tuberculosis in captive asian elephants (Elephas maximus). J. Zoo Wildl. Med. 32: 1-16.
2. Oh, P., R. Granich, J. Scott, B. Sun, M. Joseph, C. Stringfield, S. Thisdell, J. Staley, D. Workman-Malcolm, L. Borenstein, E. Lehnkering, P. Ryan, J. Soukup, A.Nitta, J. Flood. 2002. Human exposure following Mycobacterium tuberculosis infection of multiple animal species in a metropolitan zoo. Emerging Infectious Diseases. 8 (11): 1290-1293.orte

Guidelines for the control of tuberculosis in elephants.  2003.
Ref Type: Electronic Citation

Bechert, U., Christensen, J.M., Finnegan, M. Pharmacokinetics of orally administered ibuprofen in elephants. Proc Amer Assoc Zoo Vet.  84-85. 2003.
Ref Type: Conference Proceeding
Abstract: Musculoskeletal disorders (e.g., trauma, arthritis) occur commonly in captive elephants, affecting 73% of the animals studied in 69 zoos in North America.¹  To treat these and other conditions, non-steroidal anti-inflammatory agents (e.g., ibuprofen and phenylbutazone) are used strictly on an empirical basis in elephants.  There is some indication that species differences in drug metabolism exist between African (Loxodonta africana) and Asian (Elephas maximus) elephants, although this has not been substantiated.²  Determination of safe and therapeutic dosing regimens for ibuprofen and phenylbutazone will improve medical management of captive elephants by providing efficacious dosage regimens, improved control of pain, and prevention of potential toxic side effects resulting from improper drug administration. The purpose of this study was: 1) to determine the pharmacokinetic parameters of ibuprofen administered per os in elephants, and 2) to establish therapeutic dosage regimens for African (Loxodonta africana) and Asian (Elephas maximus ) male and female elephants.  Twenty healthy elephants (five males and five females of each species) housed in zoos throughout North America were used in this study.  Pilot studies were conducted at the Oregon Zoo with Asian elephants using empirically derived dosing regimens and preceded each set of clinical trials to ensure that proper ranges for dosage and dosing frequency determinations would be utilized.  Therapeutic dosage requirements were determined using 4, 5 and 6 mg/kg dosages in each animal, and blood samples were collected at –5, 15, 30, 45, 60 minutes, 1½, 2, 4, 10, 12, 24 and 48 hours post-oral administration from superficial ear veins.  Optimal dosing frequency was then determined by conducting 12 and 24 hour dosing interval trials, with blood samples collected hourly for 4 hours after each of three administrations, then every 6 hours plus 1 hour prior to the next administration.  Washout periods between all trials were 3 weeks in duration and allowed for complete elimination of residual drug metabolites. Following administration of 4 mg/kg ibuprofen and a rapid absorption phase, mean ibuprofen serum concentrations peaked in African and Asian elephants at 4 hrs at 16.75 ± 6.79 μg/mL (mean ± SD).  Five mg/kg dosages of ibuprofen resulted in peak serum concentrations of 17.20 ± 7.78 μg/mL, and with 6 mg/kg dosages, serum concentrations increased to 22.42 ± 12.30 μg/mL.  Ibuprofen was eliminated with first-order kinetics characteristic of a single-compartment model with a half-life of 4 to 4.5 hrs.  The volume of distribution (V_d/F) was estimated to be 200.8 ± 101.17 mL/kg for African and 164.4 ± 34.60 mL/kg for Asian elephants.  The doses used in this study with elephants resulted in serum concentrations at or above therapeutic concentrations for humans (15-30 mg/L) for up to 12 hrs.  Serum ibuprofen concentrations decreased to below 5 μg/mL 24 hr post-administration in all elephants.  There were no statistically significant pharmacokinetic parameter differences between males and females of either species, and differences between African and Asian elephants existed but were not significant (p < 0.12).  The mean AUC and t_1/2 life values for Asian elephants were higher as compared to African elephants, and the mean clearance and elimination rate constant were lower in Asian elephants as compared to African elephants.  Ibuprofen administered at 6 mg/kg/12 hrs for Asian elephants and at 7 mg/kg/12 hrs for African elephants resulted in therapeutic serum concentrations of this anti-inflammatory agent.  Acknowledgments:The elephant keeper staff at the Kansas City Zoo, Riddle's Elephant Sanctuary, the Bowmanville Zoo, Pittsburgh Zoo, Have Trunk Will Travel, and Oregon Zoo did a great job collecting the blood samples for this study.  The Morris Animal Foundation funded this research. References: 1.Mikota, S.K., E.L. Sargent, and G.S. Ranglack.  1994.  Medical Management of the Elephant.  Indira Publishing House, West Bloomfield, Michigan, pp. 137-150. 2.Mortenson, J., and S. Sierra.  1998.  Determining dosages for anti-inflammatory agents in elephants.  Proc Am Assoc Zoo Vet, pp. 477-479.

Chakraborty, A., 2003. Diseases of elephants (Elephas maximus) in India-A Review. Indian Wildlife Year Book 2, 74-82.

Mahanta, P.N., 2003. Health monitoring and common diseases in free ranging elephants. In: Das, D. (Ed.), Healthcare, Breeding and Management of Asian Elephants. Project Elephant. Govt. of India, New Delhi, pp. 130-136.

Michel, A.L., Venter, L., Espie, I.W., 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, 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.

Mikota, S.K., Hammatt, H., Finnegan, M. Occurrence and prevention of capture wounds in Sumatran elephants (Elephas maximus sumatranus). Proc Amer Assoc Zoo Vet.  291-293. 2003.
Ref Type: Conference Proceeding
Abstract: The capturing of elephants in Indonesia began in 1986 as an attempted solution to human-elephant conflict.  The intent was to train "problem" elephants for use in agriculture, logging and tourism.  The initial captures were conducted under the guidance of Thai mahouts and Thai koonkie elephants (trained elephants used for capture).  A number of the Indonesians that were originally trained in capture techniques still work for the government forestry department (KSDA).  The younger pawangs (elephant handlers) that participate in captures have learned from their peers.  There is no formal training program. The actual mortality rate associated with elephant captures in Sumatra is unknown as official reports are lacking.  The age structure of the existing ~ 400 captive elephants is young (most under 25) which suggests that smaller, younger elephants are preferentially captured and / or that adult elephants do not survive the capture and training processes.  Our personal experiences (Mikota and Hammatt) in Sumatra show that mortality in newly captured elephants is high.In 2001, with endorsement from the World Wide Fund for Nature-Indonesia (WWF), the Wildlife Conservation Society (WCS), Fauna and Flora International (FFI), and the International Elephant Foundation (IEF), we requested a two-year Moratorium on elephant captures during which time capture techniques would be improved and alternative conflict mediation techniques evaluated.
A Moratorium against placing additional elephants into the Elephant Training Centers has been issued by the central government, however capture for translocation is still sanctioned.  Unfortunately, the provincial governments have increasingly acted in their own interests since the government of Indonesia began a de-centralization process a few years ago. Riau Province is thought to have the largest remaining populations of wild Sumatran elephants.Fifty-seven, human-elephant conflicts occurred in Riau between 1997-2000.  Although Riau is a hotbed of conflict, problems are occurring throughout Sumatra and we are aware of conflicts and captures in Bengkulu and North Sumatra. In October 2002, we were invited by KSDA (the provincial forestry department) to accompany their team into the field as they attempted to capture a large bull that had been raiding a palm oil plantation.  This opportunity was invaluable as we were able to observe first hand the techniques being used and where improvements were needed.  As a result of this and other experiences with newly captured elephants we observed: ·Equipment (Palmer) is old, poorly maintained, and used improperly. · Essential supplies are lacking or homemade substitutes are used.
·The dose of xylazine is very high compared to wild elephant capture doses used in India and Malaysia.  The same dose is often used regardless of the size of the elephant. ·The needles are too short to reach muscle; open-ended needles are used which can become plugged with tissue, thus preventing injection. ·Neither the correct charge nor the correct load is selected.  We observed that many darts bounced making it difficult to ascertain the amount of drug injected or its depth of penetration.  Selection of an inappropriate charge results in unnecessary trauma. ·The preparation and use of darts, needles, and syringes lacks basic hygiene. ·Dart wounds are not treated and antibiotics are not administered.  · There is no understanding of stress or capture myopathy. ·The capture team was not aware that sternal recumbency severely compromises respiration in elephants and that they can quickly die in this position. ·It is believed that elephant restraints must inflict pain to prevent wild elephants from escaping once captured.  ·There is no veterinarian on the capture team. The current capture techniques result in leg wounds from unprotected chains, neck wounds from "kahs" (neck yokes made of wood and wire), and abscesses from inappropriately administered darts.  Leg and neck wounds often become maggot infested.  Infections from dart wounds are, however, the primary cause of capture-related mortality.  These abscesses can drain for several months, even with treatment, and often progress to a necrotizing fasciitis, acute sepsis, and death. The Riau Province KSDA Team has been receptive to suggested changes to minimize wounds. Provision of heavier chains has alleviated the fear that elephants will escape.  Covering the chains with fire hose or heavy plastic minimizes injuries to legs and use of the kah has been discontinued.  A basic dart wound treatment protocol has been established. In June 2003, a comprehensive Elephant Immobilization and Translocation Workshop for Sumatra is planned to retrain all of Sumatra's field teams and to upgrade equipment. Sumatra's wild elephant population probably numbers fewer than 3000 and is under continued threat.  With so few elephants left, the preservation of as many viable herds as possible takes on increased urgency.  The Moratorium achieved in 2001 has set the groundwork for KSDA to choose translocation of wild elephants rather than capture and placement into already over-crowded and under-resourced Elephant Training Centers.  We cannot guarantee that Sumatra will capture elephants only for translocation, and it is inevitable that many more elephants will end up in captivity.  Regardless, all of the elephants that must suffer the interruption of their lives at the hand of man deserve, at the very least, humane treatment.  Translocations are neither simple nor a complete panacea.  Identifying suitable translocation areas and insuring that elephants remain there are significant challenges.  WWF-Indonesia is continuing its efforts to secure the lowland forest of Tesso Nilo in Riau Province as a "safe haven" for at least some of Sumatra's wild elephants (see WWF AREAS Program – Riau, Sumatra: http://www.worldwildlife.org/species/attachments/riau_profile.pdf).  The identification of interim release sites, together with improved capture techniques, offers the hope that fewer elephants will be removed from the wild.   ACKNOWLEDGMENTS: Our work in Sumatra has been supported by the Guggenheim Foundation, a CEF grant from the American Zoo and Aquarium Association, the International Elephant Foundation, Oregon Zoo, Columbus Zoo, Disney, Peace River Refuge, the Elephant Managers Association, the Riddles Elephant and Wildlife Sanctuary, Tulsa Zoo, Toronto Zoo, Niabi Zoo, San Antonio Zoo, Denver Zoo (AAZK Chapter), Milwaukee Zoo (AAZK Chapter), the Audubon Nature Institute (Youth Volunteers), Buttonwood Park Zoo, Melbourne Zoo, and private donors.  Special thanks to Harry Peachey, John Lehnhardt, Holly Reed, Kay Backues, Mike Keele, Steve Osofsky, and Heidi and Scott Riddle.

Nath, I., Bose, V.S.C., Panda, S.K., Das, B.C., Singh, L.A.K., 2003. A case of multiple abscesses in a baby elephant. Zoos' Print Journal 18, 1270.

Pavlik, I., Ayele, W.Y., Parmova, I., Melicharek, I., Hanzlikova, M., Svejnochova, M., Kormendy, B., 2003. Mycobacterium tuberculosis in animal and human populations in six Central European countries during 1990-1999. Veterinarni Medicina 48, 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.

Potters, D., Seghers, M., Muyldermans, G., Pie´rard, D., Naessens, A., Lauwers, S., 2003. Recovery of Mycobacterium elephantis from sputum of a patient in belgium. Journal of Clinical Microbiology 41, 1344.
Abstract: Mycobacterium elephantis was isolated from a human respiratory specimen in April 1999, demonstrating its presence in Europe. The biochemical reaction results, antimicrobial susceptibility pattern, and sequence data for this strain are all in agreement with those of M. elephantis strains isolated previously from other continents.

Rahman, T., 2003. Infectious and non-infectious disease of elephants. In: Das, D. (Ed.), Healthcare, Breeding and Management of Asian Elephants. Project Elephant. Govt. of India, New Delhi, pp. 108-118.

Rehman, A., 2003. Disease control program of elephants. In: Das, D. (Ed.), Healthcare, Breeding and Management of Asian Elephants. Project Elephant. Govt. of India, New Delhi, pp. 152-156.

Schmitt, D.L., 2003. Proboscidea (Elephants). In: Fowler, M.E., Miller, R.E. (Eds.), Zoo and Wild Animal Medicine. Elsevier Science USA, pp. 541-550.

Sleeman, J.M., Clyde, V.L., Finnegan, M.V., Ramsay, E.C., Shires, M.G., 2003. Mammary botryomycosis and mastectomy in an African elephant (Loxodonta africana). Vet Rec 152, 54-55.

Vodicka, R., Kral, J., 2003. Purulent trunk dermatitis in a male Ceylon elephant (Elephas maximus). Verh. ber. Erkrg. Zootiere 41, 151-153.
Abstract: A report in given on the therapy of purulent trunk dermatitis in an aggressive male Ceylon elephant. Despite the non-standard steps we took (repeated anaesthesias during a short time, non-compliance with the recommendations as to the application of some drugs, etc.) and the difficult handling (an aggressive; incontrollable elephant, no restraint chute), it is possible even to treat a case like this.

Ziccardi, M., Wong, H.N., Tell, L.A., Fritcher, D., Blanchard, J., Kilbourn, A., Godfrey, H.P. Further optimization and validation of the antigen 85 immunoassay for diagnosing mycobacteriosis in wildlife. Proc Amer Assoc Zoo Vet.  219-220. 2003.
Ref Type: Conference Proceeding
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 19^th 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.

LITERATURE CITED

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.

Alexander, K.A., Pleydell, E., Williams, M.C., Lane, E.P., Nyange, J.F.C., Michel, A.L., 2002. Mycobacterium tuberculosis : An Emerging Disease of Free-Ranging Wildlife. Emerging Infectious Diseases 8, 598-601.
Abstract: Expansion of ecotourism-based industries, changes in land-use practices, and escalating competition for resources have increased contact between free-ranging wildlife and humans. Although human presence in wildlife areas may provide an important economic benefit through ecotourism, exposure to human pathogens
may represent a health risk for wildlife. This report is the first to document introduction of a primary human pathogen into free-ranging wildlife. We describe outbreaks of Mycobacterium tuberculosis, a human pathogen, in free-ranging banded mongooses (Mungos mungo) in Botswana and suricates (Suricata suricatta) in South Africa. Wildlife managers and scientists must address the potential threat that humans pose to the health of free-ranging wildlife.

Auclair, B., Mikota, S., Peloquin, C.A., Aguilar, R., Maslow, J.N., 2002. Population pharmacokinetics of antituberculous drugs and treatment of Mycobacterium bovis  infection in Bongo Antelope (Tragelaphus eurycrus isaaci ). Journal of Zoo and Wildlife Medicine 33, 193-203.

Benkirane, A., de Alwis, M.C.L., 2002. Haemorrhagic septicaemia, its significance, prevention and control in Asia. Vet. Med. -Czech 47 , 234-240.
Abstract: Haemorrhagic septicaemia (HS) is an endemic disease in most countries of Asia and sub Saharan Africa. Within the Asian Region, countries can be classified into three categories, on the basis of incidence and distribution of the disease; these are respectively countries where the disease is endemic or sporadic, clinically suspected but not confirmed, or free. Economic losses due to HS are not only confined to losses to the animal industry, but also rice production on account of its high prevalence among draught animals used in rice fields. Only a few attempts have been made to estimate economic losses, the methodologies used in different countries have varied, and many are not based on active surveillance, and a consideration of all components of direct and indirect losses. Most Asian countries rank HS as the most important contagious disease or the most important bacterial disease in cattle and buffaloes. Resource allocation for prevention and control of HS nationally or internationally will evidently depend on a correct estimate of its economic impact. The key factors in prevention and control would be timely and correct reporting, accurate and rapid diagnosis, strategic use of vaccines with the attainment of a high coverage where necessary with a high quality vaccine. National level activities geared towards attainment of these objectives may be with advantage supported and strengthened by international organisations involved in animal health. ?e present paper attempts to review aspects related to the epidemiology, control and containment of HS in Asia and, proposes some key issues on which a regional programme for HS control in this continent should be centred.

Chandrasekharan, K., 2002. Specific diseases of Asian elephants. Journal of Indian Veterinary Association Kerala 7, 31-34.
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.

Gavier-Widen, D., Hard Af Segerstad, C., Roken, B., Moller, T., Bolske, G., Sternberg, S. Mycobacterium tuberculosis infection in Asian elephants (Elephas maximus) in Sweden. European Association of Zoo and Wildlife Veterinarians 4th Scientific Meeting.  2002. Heidelberg, Germany.
Ref Type: Conference Proceeding

Mikota, S.K., Maslow, J. Epidemiology and Treatment of Tuberculosis in Elephants: 2002. Baer, C. K. American Association of Zoo Veterinarians Annual Conference.  384-387. 2002. 2002.
Ref Type: Conference Proceeding

Nayar, K.N.M., Chandrasekharan, K., Radhakrishnan, K., 2002. Management of surgical affections in captive elephants. Journal of Indian Veterinary Association Kerala 7, 55-59.

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., Flood, J., 2002. Human exposure following Mycobacterium tuberculosis infection of multiple animal species in a Metropolitan Zoo. Emerg Infect Dis 8, 1290-1293.
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.

Payeur, J.B., Jarnagin, J.L., Marquardt, J.G., 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.

Peloquin, CA., 2002. Therapeutic drug monitoring in the treatment of tuberculosis. Drugs 62, 2169-2183.

Singh, V.N., 2002. Symptomatic study of haemorrhagic septicaemia in elephant in Mudumalai Wildlife Sanctuary, Tamil Nadu. Indian Forester 128, 1089-1100.
Abstract: Symptoms of haemorrhagic septicaemia, a dreaded disease in elephant is recorded in this study which reveals systematic spread of Oedema from jowl to throat, neck, brisket, abdomen and perenical regions. It also records the changes in character/colour of dung, urine, eye, tongue, trunk, body temperature, feeding habit and body condition along with treatment given to cure the disease.

Tuntivanich, P., Soontornvipart, K., Tuntivanich, N., Wongaumnuaykul, S., Briksawan, P., 2002. Conjunctival microflora in clinically normal Asian elephants in Thailand. Veterinary Research Communications 26, 251-254.
Abstract: The objective of the study is to determine the population of microbial flora present in the healthy conjunctival sacs of elephants in Thailand. 44 elephants with normal eyes were studied. Of the 79 swabs cultured, 63 (88.8%) were positive for aerobic bacteria or yeasts, while no organisms were isolated from 16 eyes (11.2%). Gram-positive organisms, predominantly Staphylococcus spp. and Corynebacterium spp., accounted from more then 50% of the total number of isolates. Acinetobacter lwoffii was the main Gram -negative bacterium identified. The presence of yeast was also evident.

Turenne, C., Chedore, P., Wolfe, J., Jamieson, F., May, K., Kabani, A., 2002. Phenotypic and molecular characterization of clinical isolates of Mycobacterium elephantis from human specimens. J Clin Microbiol 40, 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.

Bacciarini, L.N., Pagan, O., Frey, J., Grone, A., 2001. Clostridium perfringens beta2-toxin in an African elephant (Loxodonta africana)with ulcerative enteritis. Vet Rec 149, 618-620.
Abstract: A 22-year-old female African elephant (Loxodonta africana) developed diarrhea of unknown cause which lasted for two days. The animal was euthanized after it remained recumbent and refused to get up. Gross pathological changes were present mainly in the gastrointestinal tract. The intestinal contents were watery and dark brown. Several areas of the mucosa of the small intestine were covered minimally to moderately with fibrin and had a few 0.1 x 10 to 15 cm linear ulcerations. Microscopical lesions consisted of discrete areas of necrosis of the surface and crypt epithelium without overt inflammatory infiltrates. Culture of the small intestinal contents resulted in a moderate growth of Clostridium perfringens. No salmonella were found in the small or large intestine. PCR of the isolate of C. perfringens revealed the presence of the beta2-toxin gene cpb2 and the alpha-toxin gene cpa but no other known toxin genes. The expression of the beta2-toxin gene in vivo was demonstrated by the immunohistochemical localization of the beta2-toxin to the microscopical lesions in the small intestine.

Clifton-Hadley, R.S., Sauter-Louis, C.M., Lugton, I.W., Jacson, R., Durr, P.A., Wilesmith, J.W., 2001. Mycobacterial diseases. In: Williams, E.S. (Ed.), Infectious Diseases of Wild Mammals. Iowa State University Press, Ames, Iowa, pp. 340-361.

Davis, M., 2001. Mycobacterium tuberculosis risk for elephant handlers and veterinarians. Appl Occup Environ Hyg 16, 350-353.

Harr, K., Isaza, R., Harvey, J. Clinicopathological findings in Mycobacterium tuberculosis culture-positive elephants (Elephas maximus) in comparison to clinically normal elephants. Kirk Baer, C. and Wilmette, M. W. 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.  209-211. 2001.  American Association of Zoo Veterinarians.
Ref Type: Conference Proceeding

Hecht, J. Telltale bones. New Scientist [2312], 14. 2001.
Ref Type: Magazine Article

Isaza, R. The elephant trunk wash - An update. ProcElephant Mangers Association Annual Conference.  2001.
Ref Type: Conference Proceeding

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., Maslow, J., 2001. Epidemiology and diagnosis of Mycobacterium tuberculosis in captive Asian elephants (Elephas maximus). Journal of Zoo and Wildlife Medicine 32, 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.

Miller, M., Neiffer, D., Weber, M., Fontenot, D., Stetter, M., Bolling, J. Salmonella Culture and PCR Results in a Group of Captive African Elephants (Loxodonta africana). A Research Update on Elephants and Rhinos; Proceedings of the International Elephant and Rhino Research Symposium, Vienna, June 7-11, 2001.  83-86. 2001. Vienna, Austria, Schuling Verlag. 2001.
Ref Type: Conference Proceeding

Montali, R.J., Richman, L.K., Mikota, S.K., Schmitt, D.L., Larsen, R.S., Hildebrandt, T.B., Isaza, R., Lindsay, W.A. Management Aspects of Herpesvirus Infections and Tuberculosis in Elephants. A Research Update on Elephants and Rhinos; Proceedings of the International Elephant and Rhino Research Symposium, Vienna, June 7-11, 2001.  87-95. 2001. Vienna, Austria, Schuling Verlag. 2001.
Ref Type: Conference Proceeding
Abstract: Elephant endotheliotropic herpesvirus (EEHV) infections and tuberculosis have emerged as causes of illness and mortality in captive elephants. Twenty-six confirmed EEHV cases are documented. Since 1995, 7 have occurred in North America, 10 in Europe and 2 in Asia. A PCR test was used to detect the virus in symptomatic animals; a serological test to identify carrier elephants is under development. The African elephant is a potential source of the EEHV that is lethal for Asian elephants. Fatal infections have also occurred in Asian elephants without African elephant contacts. Three of 6 elephants recovered after treatment with antiviral famciclovir; however, more research is needed to improve the usefulness of this drug. Asian elephants that are less than 10-years old and have been moved to another facility and/or have had contact with African elephants are at increased risk for contracting EEHV. Animals traveling between facilities with a history of EEHV cases may be at greater risk. All young elephants should be monitored daily for anorexia, lethargy, body swellings and blue discoloration (bruising) of the tongue, and be trained for blood sampling and potential oral and rectal treatment with famciclovir.
Since 1996, Mycobacterium tuberculosis has affected about 3% of Asian elephants in North America. Most were from 5 U.S. States with some contacts between private herds. Mandatory annual testing for tuberculosis by trunk wash cultures was established in 1998, and 22 culture-positive M. tuberculosis elephants were identified between 1996-2001. Fifteen were treated with anti-tuberculosis drugs and 7 that died or were euthanized were proven to have tuberculosis at necropsy. Antemortem sera was available from 4/7 4 (75%) were strongly ELISA positive. Tuberculosis is uncommon in African elephants but was recently associated with M. bovis in the U.S. and M. tuberculosis in Germany. Conversely, M. bovis tuberculosis, apparently unrecognized in Asian elephants, recently occurred in Germany. Management issues of elephant tuberculosis will be discussed relative to its complex epidemiology and clinical-pathological correlations.

Montali, R.J., Mikota, S.K., Cheng, L.I., 2001. Mycobacterium tuberculosis in zoo and wildlife species. Revue Scientifique et Technique Office International des Epizooties 20, 291-303.
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 established.

Ratanakorn, P. 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.  111-114. 2001. Vienna, Austria, Schuling Verlag. 2001.
Ref Type: Conference Proceeding

Boomershine, C.S., Zwilling, B.S., 2000. Stress and the pathogenesis of tuberculosis. Clinical Microbiology Newsletter 22, 177-182.

Emanuelson, K. Protected Contact and Medical Care in Captive Elephants, with a Case Presentation of Salmonellosis in Elephants at the Oakland Zoo. Elephants: Cultural, Behavioral, and Ecological Perspectives; Program and Abstracts of the Workshop.  9. 2000. Davis, CA. 2000.
Ref Type: Conference Proceeding

Emanuelson, K.A., Kinzley, C.E. Salmonellosis and subsequent abortion in two African elephants. Proc. AAZV and IAAAM Joint Conf.  269-274. 2000.
Ref Type: Conference Proceeding

Gage, L.J., Blasko, D. Husbandry and Medical Considerations for Geriatric Elephants. Elephants: Cultural, Behavioral, and Ecological Perspectives; Program and Abstracts of the Workshop.  9-10. 2000. Davis, CA. 2000.
Ref Type: Conference Proceeding

Larsen, R.S., Salman, M.D., Mikota, S.K., Isaza, R., Montali, R.J., 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, 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.

Larsen, R.S., Salman, M.D., Mikota, S.K., Isaza, R., Triantis, J. Validation and use of a multiple-antigen ELISA for detection of tuberculosis infections in elephants. Proc. AAZV and IAAAM Joint Conf.  231-233. 2000.
Ref Type: Conference Proceeding

Lyashchenko, K., Singh, M., Colangeli, R., Gennaro, M.L., 2000. A multi-antigen print immunoassay for the development of serological diagnosis of infectious disease. Journal of Immunological Methods 242, 91-100.

Mikota, S.K., Larsen, R.S., 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.

Ronald, B.S.M., Sukumar, K., Meenachiselvan, M.S., Dorairajan, N., 2000. Isolation of Actinomyces pyogenes [Arcanobacterium pyogenes] from fistula in an elephant. Zoos' Print Journal 15, 306.

Shojaei, H., Magee, J.G., Freeman, R., Yates, M., Horadagoda, N.U., 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, 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.

Shrivastav, A.B., Chaturvedi, V.K., 2000. A case of Pasteurellosis in elephant. Indian Journal of Comparative Microbiology, Immunology and Infectious Diseases 21, 159.

Spelman, L., Yates, R., Anikis, P., Galuppo, L. Regional Digital Intravenous Perfusion in an African Elephant (Loxodonta africana). 2000 Proceedings AAZV and IAAAM Joint Conference.  388-389. 2000. 2000.
Ref Type: Conference Proceeding

Ziccardi, M., Mikota, S.K., Barbiers, R.B., Norton, T.M. Tuberculosis in zoo ungulates:Survey results and surveillance plan. Proc. AAZV and IAAAM Joint Conf.  438-441. 2000.
Ref Type: Conference Proceeding

Bhat, M.N., Manickam, R., Ramkrishna, J., 1999. Screening of captive wild animals for tuberculosis. Indian Veterinary Journal 76, 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 animals.

Biberstein, E.L., Hirsch, D.C., 1999. Mycobacterium species: The agents of animal tuberculosis. Veterinary Microbiology. Blackwell Science, Maiden, MA, pp. 158-172.

Cooper, R.A., Molan, P.C., 1999. Minimum inhibitory concentration of honey for 20 strains of Pseudomonas isolated from infected wounds. Journal of Wound Care 8, 161-164.

Cooper, R.A., Molan, P.C., Harding, K.G., 1999. Minimum inhibitory concentration of honey for 58 strains of coagulase -positive Staphylococcus aureus isolated from infected wounds. Journal of the Royal Society of Medicine 92, 283-285.

Isaza, R., Ketz, C.J., 1999. A Trunk Wash Technique for the Diagnosis of Tuberculosis in Elephants. Verh. ber. Erkrg. Zootiere 39, 121-124.

Kodikara, D.S., deSilva, N., Makuloluwa, C.A.B., Gunatilake, M., 1999. Bacterial and fungal pathogens isolated from corneal ulcerations in domesticated elephants (Elephas maximus maximus) in Sri Lanka. Veterinary Ophthalmology 2, 191-192.
Abstract: Of 140 elephants of different ages and both sexes, 36 animals (25.7%) had evidence of keratitis, corneal ulcers, corneal opacities and some had foreign bodies in their eyes. Nine elephants (6.4%) had lesions in both eyes (6.41%). Cultures for both bacteria and fungi were obtained from 26 corneal ulcers, including the nine elephants with bilateral lesions. The other 10 animals could not be restrained for sample collection. Swabs from the normal corneas of an additional 20 elephants without signs of any ophthalmic diseases were also collected. 23 of the 35 (65.71%) samples from affected corneas yielded bacterial pathogens, and 14 (40%) also had fungal isolates. None of them yielded a fungal isolate alone. The predominant bacteria isolated were Staphylococcus aureus, beta haemolytic streptococci and coliforms. Fusarium, Cladosporium, Curvularia and Aspergillus species were the primary fugal isolates. No bacteria or filamentous fungi were isolated from the eyes with the normal corneas. Microbial identification including that of fungal isolates is suggested in the management of infective corneal diseases in elephants.

Mangold, B.J., Cook, R.A., Cranfield, M.R., Huygen, K., 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 30, 477-483.
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.

Mehrotra, P.K., Mathur, B.B.L., Sudhir, B., 1999. Staphylococcal septicaemia in Asiatic elephants. Indian Journal of Animal Health 38, 175.

Mikota, S.K., 1999. Diseases of the Elephant: A Review. Verh. ber. Erkrg. Zootiere 39, 1-15.

Anonymous, 1998. TB in elephants. Communique 18.

Bhat, M.N., Manickam, R., Nedunchelliyan, S., Jayakumar, V., 1998. Detection of leptospirial antibodies in the sera of elephants. Indian Veterinary Journal 75, 201-203.
Abstract: Leptospirosis is an infectious disease of man and animals, caused by antigenically distinct members of the genus  Leptospira.  Upadhya et al (1979) detected antibody against Leptospira valbuzzi and L. pyrogenes in the sera of elephants.  Arora (1994) detected antibodies against L. pomona in a sambar and black buck.  In the present study, a serological survey was undertaken to detect antibodies against seven serovars of Leptospira sp. in elephants (Elephas maximus), spotted deer (Axis axis), and blackbucks (Antelope cervicapra). Serum samples were collected from 109 elephants in 15 elephant camps in Madras, Karnataka, and the Andaman and Nicobar Islands, and from 4 spotted deer and 4 blackbuck in a zoo in Madras. In 23 (21%) of the elephants, antibodies, at titres of 1:100 to 1:200, were found by microscopic agglutination tests, to 6 serovars of Leptospira interrogans: pomona, icterohaemorrhagiae, grippotyphosa, hebdomadis, hardjo, and canicola. No leptospiral antibodies were found in the serum of the other animals. Clinical signs were present only in the elephants with L. grippotyphosa; the other serovars are reported for the first time in Indian elephants.

Das, S., Kalita, D., Barman, N.N., Sarma, B., 1998. Isolation of Pseudomonas aeruginosa from an affected tusk of elephant. J Comp Microbiol Immunol Infect Dis 19, 129.

Dunker, F., Rudovsky, M. Management and treatment of a Mycobacterium tuberculosis positive elephant at the San Francisco Zoo.  Proceedings AAZV and AAWV Joint Conference.  122-123. 1998.
Ref Type: Conference Proceeding

Jacobson, R.H., 1998. Validation of serological assays for diagnosis of infectious diseases. Rev. sci. tech. Off. int. Epiz. 17, 469-486.

Mahato, G., Rahman, H., Sharma, K.K., 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, 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.

Matsuo, K., Hayashi, S., Kamiya, M., 1998. Parasitic infections of Sumatran elephant in the Way Kambas National Park, Indonesia. Japanese Journal of Zoo and Wildlife Medicine 3, 95-100.
Abstract: In 1995, 3 Sumatran elephants (Elephas maximus sumatranus) died suddenly of clostridial infection in the Way Kambas National Park, Lampung province, Indonesia. Postmortem examination revealed that the gastrointestinal tracts of all 3 animals were also infected with Murshidia falcifera (Nematoda), Hawkesius hawkesi and Pfenderius papillatus (Digenea) and Cobboldia elephantis (Diptera). The elephant louse, Haematomyzus elephantis, was a common cause of dermatopathy in elephants kept in the national park.

Mbise, A.N., Mlengeya, T.D.K., Mollel, J.O., 1998. Septicaemic salmonellosis of elephants in Tanzania. Bulletin of Animal Health and Production in Africa 46, 95-100.
Abstract: The first isolation of Salmonella enterica subsp. enterica serovar typhimurium (S. typhimurium) from an African elephant (Loxodanta africana) that died in August 1997 at the Tarangire National Park near a campsite in Northern Tanzania is reported. This and other findings suggest the potential role of wildlife in the epidemiology of Salmonella sp. infections. Also, the isolation of this S. typhimurium serovar as a zoonosis demonstrates the danger that humans and animals in the Tarangire ecosystem are exposed to, as this serovar is ubiquitous among different species of animals.

Michalak, K., Austin, C., Diesel, S., Bacon, M.J., Zimmerman, P., Maslow, J.N., 1998. Mycobacterium tuberculosis infection as a zoonotic disease: transmission between humans and elephants. Emerg Infect Dis 4, 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.

Montali, R.J., Spelman, L.H., Cambre, R.C., Chattergee, D., Mikota, S.K. Factors influencing interpretation of indirect testing methods for tuberculosis in elephants. Proceedings AAZV and AAWV Joint Conference.  109-112. 1998.
Ref Type: Conference Proceeding
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 points.

Sutopa, D., Kalita, D., Barman, N.N., Sarmah, B., Das, S., 1998. Isolation of Pseudomonas organism from an affected tusk of an elephant. Indian Journal of Comparative Microbiology, Immunology and Infectious Diseases 19, 129.

Wright, P.F., 1998. International standrads for test methods and reference sera for diagnostic tests for antibody detection. Rev. sci. tech. Off. int. Epiz. 17, 527-533.

Binkley, M. Tuberculosis in captive elephants. Proceedings American Association of Zoo Veterinarians.  116-119. 1997.
Ref Type: Conference Proceeding

Essey, M.A., Davis, J.P. Status of the National cooperative state-federal bovine tuberculosis eradication program fiscal year 1997. Proceedings United States Animal Health Association.  564. 1997.
Ref Type: Conference Proceeding

Furley, C.W., 1997. Tuberculosis in elephants. Lancet British edition 350, 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.

Keet, D.F., Grobler, D.G., Raath, J.P., Gouws, J., Carstens, J., Nesbit, J.W., 1997. Ulcerative pododermatitis in free-ranging African elephant (Loxodonta africana) in the Kruger National Park. Onderstepoort Journal of Veterinary Research 64, 25-32.
Abstract: The occurrence of severe lameness in adult African elephant bulls in a shrub Mopane (Colophospermum mopane) ecosystem was investigated. Large ulcers in the soles of at least one front foot were seen in each of the recorded cases. Microscopically, the lesion can be described as a severe, chronic-active, ulcerative, bacterial pododermatitis (complicated by hypersensitivity/septic vasculitis). A variety of bacteria were isolated from these lesions as well as from regional lymph nodes. Streptococcus agalactiae was the most consistent isolate, while Dichelobacter nodosus, the only organism known to be involved with foot disease in domestic ruminants, was isolated from two cases. Contributory factors such as body mass, portal of entry and origin of potential pathogens may have predisposed to the development of the lesions.

Maslow, J. Tuberculosis and other mycobacteria as zoonoses. Proceedings American Association of Zoo Veterinarians.  110-115. 1997.
Ref Type: Conference Proceeding
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.

Mikota, S.K., Maslow, J. Theoretical and technical aspects of diagnostic techniques for mammalian tuberculosis. Proceedings, American Association Zoo Veterinarians.  162-165. 1997.
Ref Type: Conference Proceeding

Pagan, O., Heldstab, A., Vollm, J., Weiser, T., Hockenjos, P. Salmonellosis in elephants: possibilities and limits of control. Erkrankungen der Zootiere: Verhandlungsbericht des 38. Internationalen Symposiums uber die Erkrankungen der Zoo- und Wildtiere von 7 bis 11 Mai 1997, in Zurich, Schweiz.  305-310. 1997. Berlin,  Germany, Institut fuer Zoo und Wildtierforschung im Forschungsverbund Berlin e.V.; Berlin; Germany.
Ref Type: Conference Proceeding

Peloquin, CA., 1997. Using therapeutic drug monitoring to dose the antimycobacterial drugs. Clinics in Chest Medicine 18,  79-97.

Ryan, C.P., 1997. Tuberculosis in circus elephants. Pulse Southern California Veterinary Medical Assoc. 8.

Whipple, D.L., Meyer, R.M., Berry, D.F., Jarnagin, J.L., Payeur, J.B. 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.  543-546. 1997. Richmond, VA,USA, United States Animal Health Association.
Ref Type: Conference Proceeding

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., 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.

Kirchhoff, H., Schmidt, R., Lehmann, H., Clark, H., Hill, A.C., 1996. Mycoplasma elephantis sp. nov., a new species from elephants.  Journal of Systematic Bacteriology 46, 437-441.
Abstract: Organisms with the typical characteristics of mycoplasmas were isolated from the genital tracts of female elephants.  The results of growth inhibition tests, metabolic inhibition tests, indirect immunoflourescence tests, and immunobinding assays showed that the isolated mycoplasmas were identical and distinct from previously described Mycoplasma, Entoplasma, Mesoplasma, and Acholeplasma species.  These organisms represent a new species, for which the name Mycoplasma elephantis is proposed.  M. elephantis ferments glucose, fructose, maltose, mannos, and sucrose, produces films and spots, does not hydrolyze arginine, esculin, and urea, does not reduce methylene blue, tetrazolium chloride, and potassium tellurite, does not possess phosphatase activity, and reduces resazurin.  It lyses avian, ovine, and guinea pig erythrocytes.  It does not absorb erythrocytes.  Cholesterol or serum is required for growth.  The optimum growth temperature is 37 degrees C.  The G+C content of the DNA is 24.0 mol%.  The type strain of M. elephantis is E42 (= ATCC 51980.

Kubinski, T., Maciak, T., Sawicka-Wrzosek, K., 1996. Microbial flora isolated postmortem from internal organs in zoo animals in Warsaw. Magazyn Weterynaryjny 5, 236-240.

Moda, G., Daborn, C.J., Grange, J.M., 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.

Murray, S., Bush, M., Tell, L.A., 1996. Medical management of postpartum problems in an Asian elephant (Elephas maximus) cow and calf. Journal of Zoo and Wildlife Medicine 27, 255-258.
Abstract: An 18-yr old female Asian elephant (Elephas maximus) gave birth to a 120-kg female calf following 22 mo of gestation.  Immediately after parturition, the cow became agitated and aggressive towards the calf.  Before the keepers were able to safely intervene and remove the calf, the cow stepped on the calf's head and right front leg.  Within 30 min, the cow calmed down, allowing the calf's safe reintroduction under close keeper supervision and control.  The cow had a retained placenta, poor mammary development, and low milk production.  The calf's injuries, in combination with the cow's low milk production, impeded the calf's ability to nurse and gain weight.  Within 10 days, the calf lost 10% of its weight.  Serum protein electrophoresis indicated failure of passive transfer of maternal immunoglobulin.  On day 10, the calf received a transfusion of concentrated immunoglobulin extracted and concentrated from the cow's previously banked plasma.  On day 13, the calf developed a urinary tract infection, as diagnosed by white blood cells and bacteria in the urine.  Following immunoglobulin administration and antibiotic therapy, clinical signs slowly resolved and the calf gained weight.  The cow passed the fetal membranes during parturition, but the placenta was retained.  Despite prophylactic systemic antibiotics and vaginal flushing, the cow became depressed and developed a leukocytosis and anemia.  A mucopurulent vaginal discharge and ventral edema were noted on day 3, and milk production was minimal.  Because decreased milk production has been reported as a common sequel to retained placenta, efforts were focused on removing the placenta.  Intermittent oxytocin therapy on days 2-14 did not result in expulsion of the placenta and produced only transient abdominal contractions and minimal increases in milk letdown.  On day 15, 10 mg estradiol cypionate was administered i.m. followed by 200 IU oxytocin i.v.  An additional 10 IU oxytocin was administered i.v. on day 16.  The friable placenta was palpable within the vaginal vault on day 17.  The remaining placenta was removed by gentle traction applied by a modified weighted pressure cuff.  Once the placenta was removed, the cow's clinical problems slowly resolved and the calf continued to gain weight.

Sandin, R.L., 1996. Polymerase chain reaction and other amplification techniques in mycobacteriology. Clinical Mycobacteriology 16, 617-639.

Singhal, N., 1996. Treatment of an injured wild elephant in north Bengal forests. Indian Forester, Special issue: wildlife management. 122, 969-970.
Abstract: A note is given on the treatment of a solitary male wild elephant found in Panighata Resume land forest with a badly injured foreleg knee joint, possibly caused by a gunshot wound. The elephant was immobilized with a dart of Immobilon, and the wound cleaned and washed with iodine solution, and treated with 500 g of povidine iodine ointment and a fly repellent (surgicare). The animal was also given dexa-methazone (5 ml) intravenously, and Decadron (12 ml), Oxy-Vet (30 ml) and tetanus toxoid intramuscularly. The operation lasted 54 minutes, after which the animal was revived with Revivon, and later offered bananas and banana culms. The animal has made a full recovery.

Suedmeyer, K., 1996. Salmonella typimurium infection in an African elephant. Journal of the Elephant Managers Association 7, 50-52.

Zheng, X., Zheng, X.C., 1996. Diagnosis and preventative-therapeutic study of periarthritis in the shoulder of an Asian elephant. Chinese Journal of Zoology 31, 45-49.

Chakraborty, A., Sarma, D.K., 1995. Escherichia coli serotypes in captive herbivorous animals. Indian Journal of Comparative Microbiology, Immunology and Infectious Diseases 16, 87-88.

Chandrasekharan, K., Radhakrishnan, K., Cheeran, J.V., Nair, K.N.M., 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. (Ed.), A Week with Elephants; Proceedings of the International Seminar on Asian Elephants. Bombay Natural History Society; Oxford University Press, Bombay, India, 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.

Gage, L.J., Blasko, D., Fowler, M.E., Pascoe, J. Surgical removal of infected phalanges from an Asian elephant (Elephas maximus). Proc Joint Conference AAZV / WDZ / AAWV.  English. 1995.
Ref Type: Conference Proceeding

Grobler, D.G., Raath, J.P., Braack, L.E.O., Keet, D.F., Gerdes, G.H., Barnard, B.J.H., Krick, N.P.J., Jardine, J., Swanepoet, R., 1995. An outbreak of encephalomyocarditis-virus infection in free ranging African elephants in the Kruger National Park. Onderstepoort Journal of Veterinary Research 62, 97-108.
Abstract: An increase in unexplained elephant mortality was seen in the Kruger National Park (KNP) from December 1993 to November 1994, concurrent with a wide-spread increase in the KNP rodent population.  The majority of animals were found dead.  Examination of carcasses ruled out common causes of death, including poaching, anthrax, intraspecific fighting, and intoxication.  Sixty-four animals died from unexplained causes during the perceived outbreak, 83% of which were adult bulls.  Eight carcasses were in sufficiently good condition for tissues to be collected for diagnostic testing.  Cardiac failure appeared to be the most likely cause of death in seven of the animals, with gross findings of pulmonary edema, hepatic congestion, ascities, and hydrothorax.  Myocarditis and necrosis of myocytes were the most striking findings on histopathological examination.  Heart tissue from three animals was submitted for virus isolation; all three yielded encephalomyocarditis (EMC) virus.  Serologic testing for EMC virus antibody was performed on the KNP between 1984 and 1994.  Results demonstrated that the virus has  been present in the KNP from 1987 on.  EMC virus antibody was not detected in preserved rodent tissues until 1993, prior to the rodent population explosion and the outbreak of disease in elephants.  It is unclear whether rodents play a role in transmitting the virus to other animals or if they reflect a general circulation of the virus in multiple species in a given environment.  One lion cub which was found dead with bacterial pneumonia had a serum neutralizing antibody titer to EMC virus of 128.  It is hypothesized that this animal may have been predisposed to pneumonia through the formation of lung edema as a result of EMC virus infection.  Three lions that were seen feeding on the carcass of an elephant with lesions compatible with EMC virus infection were monitored for seroconversion, which did not occur.  EMC virus disappears rapidly from most tissues after death and probably was not present in the tissues consumed by the lions.  The predilection for male elephants could not be explained, although increased mortality among males has also been demonstrated with EMC virus in mice.

Munson, L., Karesh, W.B., Shin, S., Balke, J.M.E., Calle, P., Cambre, R.C., Cranfield, M., Citino, S., Junge, R.E., 1995. Lymphoid follicular vulvitis in African (Loxodonta africana) and Asian (Elephas maximus) elephants. Journal of Zoo and Wildlife Medicine 26, 353-358.
Abstract: Hyperemic nodules and plaques in the distal urogenital canal of African (Loxodonta africana) and Asian (Elephas maximus) elephants were investigated to determine if they represented a potentially transmissible venereal disease.  The distal urogenital canals of 29 captive Asian, 19 captive African, and 30 free-ranging African elephants were examined.  Biopsies were obtained from 10 captive Asian, four captive African, and 28 free-ranging African elephants.  Biopsies from four elephants (three Asian, one African) were examined ultrastructurally.  Bacteriologic cultures of the distal urogenital canal were performed on 15 captive elephants (nine African, six Asian), nine with lesions and six without lesions.  Hyperemic nodules and plaques were identified in the distal urogenital canals of 62% of captive Asian, 89% of captive African, and 90% of free-ranging African elephants examined, including 10 of 11 pregnant free-ranging elephants.  These lesions were characterized histopathologically by aggregates of coalescing reactive lymphoid follicles.  No viral agents were identified, and no specific bacteria were consistently associated with lesions.  These highly prevalent lesions appear to be reactions of mucosa-associated lymphoid tissues to non-specific antigenic challenges in the distal urogenital canal and appear to have no clinical significance.

Thiruthalinathan, R., Swaminathan, D., 1995. Haemorrhagic septicaemia in wild elephant-a case report. Indian Journal of Veterinary Research 4, 60-62.

 1994. Treatment of tuberculosis and tuberculosis infection in adults and children. Am J Respir Crit Care Med 149, 1359-1374.

Lindeque, P.M., Turnbull, P.C., 1994. Ecology and epidemiology of anthrax in the Etosha National Park, Namibia. Onderstepoort Journal of Veterinary Research 61, 71-83.
Abstract: Analysis of mortality records has revealed distinct patterns in the incidence of anthrax in elephant and plains ungulates.  The seasonal peak among the former is in November and the end of the dry season, while among the latter it occurs in March towards the end of the rainy season.  Among elephants, there has been a notable spread of the disease to the west of the Park.  Age and sex analysis indicate that, except for zebra, proportionally greater numbers of adult males die of anthrax among the species predominantly affected; however, zebra carcasses are difficult to sex. In a study to identify possible environmental sources of infection, B. anthracis was detected in 3.3% of 92 water and 3.0% of 230 soil samples collected at different times of the year from 23 sites not associated with known cases of anthrax.  Slight seasonal differences were noted with 5.7% positives occurring in the cold-dry period (May to August), 3.5% in the hot-dry season (September to December) and 1.4% in the hot-wet season (January to April).  Higher rates (2.6% of 73 samples) were found in water from waterholes in the western part of the Park at the time of an outbreak in elephants.  The possible importance of scavenger faeces was confirmed with >50% of vulture, jackal, and hyaena faeces collected from the vicinity of confirmed anthrax carcasses yielding B. anthracis, sometimes in substantial numbers, while no spores were found in faeces not associated with known anthrax carcasses. Despite terminal B. anthracis levels of usually >107 cfu/ml in the blood of animals dying of anthrax, spore levels in soil contaminated by such blood at sites of anthrax carcasses ranged from undetectable to a few tens of thousands.  The rapid loss of viability in soil and water of anthrax bacilli, was monitored experimentally and the importance of soil type demonstrated.  Survival and extent of sporulation of the bacilli in water were shown to be dependent on the rate at which the blood was diluted out. Other relevant parameters examined were background flora, pH and sunlight.

Mikota, S.K., Sargent, E.L., Ranglack, G.S., 1994. Medical Management of the Elephant. Indira Publishing House, West Bloomfield MI.

Rengel, J., Bohnel, H., 1994. Preliminary studies on oral immunization of wildlife against anthrax. Berliner-und-Munchener-Tierarztliche-Wochenschrift 107, 145-149.
Abstract: As a pilot trial for the vaccination of game in African game parks against anthrax, trials with guineapigs were undertaken to vaccinate the animals orally against anthrax. The vaccine was prepared with the Goettingen Bioreactor Technology in which sporulation is reached in the suspension. Guineapigs vaccinated orally or s.c. with the vaccine resisted a challenge of 1000 spores with a pathogenic field strain isolated from elephants in Zambia but died when challenged with a dose of 2500 spores. A technique was developed to identify anthrax organisms excreted with the faeces by means of gas chromatography.

Rothschild, B.M., Xiao, M.W., Shoshani, J., Xiaoming, W., 1994. Spondyloarthropathy in proboscideans. Journal of Zoo and Wildlife Medicine 25, 360-366.

Bengis, R., 1993. Care of the African elephant Loxodonta africana in captivity. The capture and care manual : capture, care, accommodation and transportation of wild African animals. Pretoria : Wildlife Decision Support Services : South African Veterinary  Foundation, Pretoria, pp. 506-511.

Bennet, D., 1993. Immune-based erosive inflammatory joint disease of the dog: canine rheumatoid arthritis.  2. Pathological investigations. Journal of Small Animal Practice 28, 909-928.
Abstract: The pathological features of 30 cases of canine rheumatoid arthritis are described.  The principle pathologic feature is a chronic symmetrical polysynovitis.  The pathological features of the joints varied in severity.  The synovial membrane generally showed villous hypertrophy with aggregates of lymphocytes and plasma cells.  Destruction of articular cartilage and bone occurred in association with a replacement granulation tissue which often produced a pannus over the articular surface. Immunofluorescence studies demonstrated complexes of IgG or IgM with C3 in synovial lining cells, macrophages, blood vessel walls and free in the extracellular tissues.  IgG and IgM producing plasma cells were also common.  Fibrinogen deposites were extensive.  The immunofluorescence findings were non-specific but support the concept of an immune complex mediated inflammation within the joints.  Investigations for bacterial, mycoplasmal and viral infections of the joints were negative.

Berry, H.H., 1993. Surveillance and control of anthrax and rabies in wild herbivores and carnivores in Namibia. Revue Scientifique et Technique Office International des Epizooties 12, 137-146.
Abstract: Anthrax has been studied intensively in Etosha National Park, Namibia since 1966; in addition, since 1975, mortality due to rabies and all other causes has been recorded, totaling 6190 deaths. Standard diagnostic procedures demonstrated that at least 811 deaths (13%) were due to anthrax and 115 deaths (2%) were caused by rabies. Of the total number of deaths due to anthrax, 97% occurred in zebra (Equus burchelli), elephant (Loxodonta africana), wildebeest (Connochaetes taurinus) and springbok (Antidorcas marsupialis) while 96% of rabies deaths occurred in kudu (Tragelaphus strepsiceros), jackal (Canis mesomelas), bat-eared fox (Otocyon megalotis) and lion (Panthera leo). Anthrax deaths were highest in the rainy season for zebra, wildebeest and springbok, while elephant mortality peaked during dry seasons. No statistical relationship existed between seasonal rainfall and overall incidence of either anthrax or rabies. Control of anthrax is limited to prophylactic inoculation when rare or endangered species are threatened. Incineration of anthrax carcasses and chemical disinfection of drinking water are not feasible at Etosha. Rabies control consists of the destruction of rabid animals and incineration of their carcasses when possible.

Ebedes, H., 1993. The use of long-acting tranquilizers in captive wild animals. The capture and care manual : capture, care, accommodation and transportation of wild African animals. Pretoria : Wildlife Decision Support Services : South African Veterinary  Foundation, Pretoria.

Ermel, R.W., Kenny, T.P., Chen, P.P., Robbins, D.L., 1993. Molecular analysis of rheumatoid factors derived from rheumatoid synovium suggests an antigen-driven response in inflamed joints. Arthritis and Rheumatism 36, 380-388.
Abstract: Objective.  Understanding the molecular genetic basis for rheumatoid factor (RF) production is necessary to a better understanding of the etiology and pathogenesis of rheumatoid arthritis (RA).  We sought to define the genetic basis for RF in RA.  Methods.  The heavy and light chain variable region genes encoding 4 human monoclonal RF were cloned and sequenced using the polymerase chain reaction and the dideoxynucleotide chain-termination method.  Results.  The heavy and light chains of the C6 RF and the light chain of the G9 RF were encoded by 3 new RF-related Ig V-region genes.  The heavy and light chains of D5 and G4 RF's were identical: most of their mutations caused amino acid substitutions.  Conclusions.  The RF-related Ig V-region gene repertoire is large and still expanding.  The data from D5 and G4 strongly suggest that these 2 RF's arise in an antigen-driven response in rheumatoid synovium.  The presumed germline V genes for C6 may represent disease-specific RF-related V genes.

Harth, M., 1993. Gold in rheumatoid arthritis: standard, substitute or sham? Journal of Rheumatology 20, 771-773.

Houck, R., 1993. Veterinary care of performing elephants. In: Fowler, M.E. (Ed.), Zoo and Wild Animal Medicine Current Therapy 3. W.B. Saunders Company, Philadelphia, PA, USA, pp. 453-454.

Okewole, P.A., Oyetunde, I.L., Irokanulo, E.A., Chima, J.C., Nwankpa, N., Laleye, Y., Bot, C., 1993. Anthrax and cowdriosis in an African elephant (Loxodonta africana). Veterinary Record 133, 168.
Abstract: In February 1992, a 15-year-old African elephant died; it was the second elephant that had died within 2 weeks at a wildlife park. Clinical signs in both elephants included frequent micturition, restlessness and weakness of the hindquarters with frequent falls. PM examination revealed ecchymosis of the epicardium, atrioventricular surfaces of the heart and serosal surfaces of the intestines and bladder with sloughing of intestinal mucosae. The liver was enlarged, ecchymotic and congested. A serosanguinous exudate with fibrin was present in the thoracic and abdominal cavities. The meninges were congested. Bacillus anthracis was cultured from tissue samples and from tissue samples from guineapigs inoculated with broth cultures of the tissue samples from the elephant. Cowdria ruminantium was identified in stained impression smears from the elephant brain. This appears to be the first report of the simultaneous occurrence of anthrax and cowdriosis in an African elephant.

Prins, H.H.T., Van-der-Jeugd, H.P., 1993. Herbivore population crashes and woodland structure in East Africa. Journal of Ecology Oxford 81, 305-314.
Abstract: From 1985 to 1991, bush encroachment was serious in Lake Manyara National Park, northern Tanzania. Shrub cover increased by about 20%. The increase was independent of initial (1985) shrub cover. Since 1987 there has been a steep decline in the number of African elephant (Loxodonta africana) in the Park due to poaching. Elephant density decreased from about 6 per km2 to about 1 per km2. However, shrub establishment, as determined from counting tree-rings, preceded poaching. Shrub establishment in two areas of the Park coincided with anthrax epidemics that drastically reduced the impala [Aepyceros melampus] population. In the northern section of the Park this occurred in 1984, in the southern section in 1977. The diameter increment of Acacia tortilis was 5.24 mm/yr, irrespective of the size of the trees. Size measurements indicated that an even-aged stand of A. tortilis established in 1961, which coincided with another anthrax outbreak among impala. Size measurements of old A. tortilis trees indicated that another even-aged stand established at the end of the 1880s. The size of trees of this stand was not significantly different from a stand in Tarangire National Park, nor from a stand near Ndutu (on the boundary between Serengeti National Park and Ngorongoro Conservation Area), also in northern Tanzania. All three stands are likely to have originated from bush establishment caused by the rinderpest pandemic at the end of the 1880s. It is suggested that seedling establishment of A. tortilis is a rare event under the prevailing conditions of high browsing pressures by ungulates such as impala. Punctuated disturbances by epidemics among these ungulates create narrow windows for seedling establishment, which may explain the occurrence of even-aged stands.

Rubin, L.A., Hawker, G.A., 1993. Stress and the immune system: preliminary observations in rheumatoid arthritis using an in vivo marker of immune activity. Arthritis and Rheumatism 3, 204-207.

Tuchili, L.M., Pandey, G.S., Sinyangwe, P.G., Kaji, T., 1993. Anthrax in cattle, wildlife and humans in Zambia. Veterinary Record 132, 487.
Abstract: In Zambia, 265 specimens of various tissues from animals and of surface water (5 samples) submitted over the period from 1987 to 1991 were examined for anthrax. 35 of the 85 were positive; 35 were in domestic animals including 33 cattle, a sheep and a pig from the Western, Southern, Central, Lusaka and North Western Provinces, and 50 in wild animals including 13 hippos, 11 kudus, 5 buffaloes, 4 elephants, 4 pukus, 4 wild dogs, 4 zebras, 3 waterbucks and 2 giraffes from South Luangwa National Park in Eastern Province. One water sample from the park was positive. Of 17 long bones from infected cattle, 5 yielded virulent, pure cultures of Bacillus anthracis. All milk samples examined were negative. Over 100 human deaths from anthrax, usually associated with eating infected meat have been recorded, mainly since 1990 in the Western and North-Western Provinces. Control measured for anthrax in wild animals after environmental contamination, including carcass disposal and adding quaternary ammonium compounds to water-holes, are suggested.

van Schaardenburg, D., Hazes, J.M.W., de Boar, A., Zwinderman, A.H., Meijers, K.A.E., Breedveld, F.C., 1993. Outcome of rheumatoid arthritis in relation to age and rheumatoid factor at diagnosis. Journal of Rheumatology 20, 45-52.
Abstract: Our retrospective followup study reports the outcome of rheumatoid arthritis (RA) in relation to age (under 60 vs 60 years and over) and rheumatoid factor status at diagnosis.  A sample of 130 adult patients with RA was assessed at a mean of 5.6 years after diagnosis.  At final evaluation disease activity and radiographic damage in seropositive patients were similar in both age groups, but functional capacity was markedly lower in the older onset group, indicating lower functional reserves in this group.  In seronegative patients the outcome was favorable in both age groups, especially in the older patients. Seropositive patients in both age groups had more disease activity, a lower functional capacity and more radiographic damage than seronegative patients; these differences were greater in the older onset patients.  The mortality in patients with RA compared to the general population (standardized mortality ratio, SMR) was higher in seropositive patients (SMR 2.78, 98% CI 1.70-4.13) but not in seronegative patients (SMR 0.45, 95% CI 0.08-1.13).  The relative risk of dying was 6 times higher in seropositive patients than in seronegative patients (95% CI 1.7-20.9).

Vaughan, J.H., 1993. Pathogenetic concepts and origins of rheumatoid factor in rheumatoid arthritis. Arthritis and Rheumatism 36, 1-6.

Arora, B.M., 1992. An overview of infectious diseases and neoplasms of the elephants (Elephas maximus) in India. In: Silas, E.G., Nair, M.K., Nirmalan, G. (Eds.), 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). Kerala Agricultural University, Trichur, India, pp. 159-161.

Cedillo, L., Gil, C., Mayagoitia, G., Giono, S., Cuellar, Y., Yanez, A., 1992. Experimental arthritis induced by Mycoplasma pneumoniae in rabbits. Journal of Rheumatology 19, 344-347.
Abstract: Experimental arthritis in rabbits was induced by M. pneumoniae.  We compared it with the arthritis produced by well known animal arthritogenic agents (M. pulmonis and M. arthritidis).  Mycoplasmas were detected in the knee joint by different techniques.  M. pneumoniae and M. pulmonis produced a chronic arthritis.  Live M. pneumoniae and M. pulmonis were recovered from the joint during all experiments. No live M. arthritidis was detected.  Live mycoplasmas play an important role in acute arthritis.  A similar pattern was shown by M. pneumoniae and M. pulmonis.  This animal model could be helpful in the study of arthritis induced by a human pathogen mycoplasma.

Chandrasekharan, K., 1992. Prevalence of infectious diseases in elephants in Kerala and their treatment. In: Silas, E.G., Nair, M.K., Nirmalan, G. (Eds.), 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). Kerala Agricultural University, Trichur, India, pp. 148-155.

Harris, E.D., Jr., 1992. Excitement in synovium: the rapid evolution of understanding of rheumatoid arthritis and expectations for therapy. Journal of Rheumatology 19, 3-5.
Abstract: Multiple events give rise to rheumatoid arthritis (RA) and many different elements create an overall pathological effect.  It is highly unlikely that a single cause for RA will be identified.  A greater appreciation of the multiple events that lead to the development of RA is opening up a number of promising points of intervention with may serve as potential alternatives to the broader-based and often toxic drugs used in RA therapy today.

Kushner, I., Dawson, N.V., 1992. Changing perspecitves in the treatment of rheumatoid arthritis. Journal of Rheumatology 19, 1831-1833.

Panayi, G.S., Lanchrury, J.S., Kingsley, G.H., 1992. The importance of the T cell in initiating and maintaining the chronic synovitis of rheumatoid arthritis. Arthritis and Rheumatism 35, 729-735.

Pruzanski, W., Vadas, P., 1992. Should tetracyclines be used in arthritis? Journal of Rheumatology 19, 1495-1497.

Ramos-Remus, C., Sibley, J., Russell, A.S., 1992. Steroids in rheumatoid arthritis: the honeymoon revisited. Journal of Rheumatology 19, 667-670.

Willix, D.J., Molan, P.C., Harfoot, C.J., 1992. Minimum concentration of honey (%, v/v) in the growth medium needed to completely inhibit the growth of various species of wound-infecting bacteria. Journal of Applied Bacteriology 73, 388-394.

Wither, J., 1992. Molecular aspects of the rheumatic diseases. Journal of Rheumatology 19, 649-650.

Anderson, S.T., Schiller, C.A., 1991. Rheumatoid-like arthritis in a lion tailed macaque. Journal of Rheumatology 18, 1247-1250.
Abstract: Abstract.  Very few satisfactory models of rheumatoid arthritis (RA) exist in nonhuman species.  It is particularly striking that nonhuman primates have only rarely been described to have disease processes resembling classic RA seen in humans.  We describe the case of a lion tailed macaque (Macaca silenus), housed at the National Zoological Park in Washington DC, that had a polyarticular inflammatory arthropathy resembling RA. Gross and histopathological examination of necropsy tissues and radiographic findings strongly suggest a rheumatoid-like disease never before described in this species.

Barile, M.F., Yoshida, H., Roth, H., 1991. Rheumatoid arthritis: New findings on the failure to isolate or detect mycoplasmas by multiple cultivation or serologic procedures and a review of the literature. Reviews of Infectious Diseases 13, 571-582.
Abstract: Using different and elaborate broth, agar, and cell culture procedures, we failed to isolate mycoplasmas, ureaplasmas, spiroplasmas, or chlamydiae from the synovial fluid of 10 patients with rheumatoid arthritis (RA) and from six patients with non-rheumatoid arthritis (NRA).  In addition, sera from 35 patients with NRA also were examined.  Although some of the sera had moderately high titers of metabolism-inhibiting antibody to some of the 10 human Mycoplasma species, especially to the common respiratory pathogen Mycoplasma pneumoniae, and to some of the eight Ureaplasma urealyticum serovars, especially serovars V and VII, there were no significant differences between titers of these antibodies in the two groups of patients.  Among RA patients serum antibody titers to M. pneumoniae were 1:32 in five and 1:16 in eight; two patients had higher synovial fluid titers (1:16) than serum titers (1:4).  The geometric mean titer (GMT) of antibody to serovar V in synovial fluid was higher in RA patients than in NRA patients, but the difference did not reach significance (P=.056).  Reports on the possible role of infectious agents in the pathogenesis of rheumatoid arthritis are reviewed.

Clark, H.W., 1991. The potential role of mycoplasmas as autoantigens and immune complexes in chronic vascular pathogenesis. American Journal of Primatology 24, 235-243.

Fowler, M.E. Tuberculosis in zoo ungulates. Essey, M. A. Bovine tuberculosis in cervidae: Proceedings of a symposium.  37-41. 1991. Washington,D.C., United States Department of Agriculture Miscellaneous Publication No. 1506.
Ref Type: Conference Proceeding

Gorina, L.G., Goncharova, S.A., Igumnov, A.V., 1991. Laboratory diagnosis of human mycoplasmoses. Vestnik Adademii Meditsinskikh Nauk SSSR 1991, 44-47.

Healey, L.A., Wilske, K.R., 1991. Evaluating combination drug therapy in rheumatoid arthritis. Journal of Rheumatology 18, 641-642.

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, 59-61.

Jarjour, W.N., Jeffries, B.D., Davis, J.S., Welch, W.J., Mimura, T., Winfield, J.B., 1991. Autoantibodies to human stress proteins. Arthritis and Rheumatism 34, 1133-1138.
Abstract: Unselected sera from patients with various rheumatic, inflammatory bowel, and autoimmune skin diseases (n=268) were examined against human cell lysate by immunoblotting procedures, to determine the prevalence of autoantibodies to stress proteins (heat-shock proteins) hsp60 (homolog of Escherichia coli groEL and Mycobacterial 65K antigens), hsp73, and hsp90.  Using standard, sensitive and specific assay conditions, IgG and IgM autoantibodies to these stress proteins were not demonstrable, or were detected infrequently, in sera from control subjects (n=36) and from patients with rheumatoid arthritis, Sjogren's syndrome, ankylosing spondylitis, Reiter's syndrome, systemic lupis erythematosus, and systemic sclerosis.  Autoantibodies to hsp60 were relatively more common (>= 20% of sera) in patients with mixed connective tissue disease, polymyositis/dermatomyositis, psoriatic arthritis, inflammatory bowel disease, epidermolysis bullosa acquista, and bullous pemphigoid.  Anti-hsp73 autoantibodies were detected in 20% or more of the sera from patients were Lyme disease and ulcerative colitis.  Taken together, these data extend the spectrum of autoimmune and inflammatory diseases in which humoral anti-stress protein reactivity develops.  However, the paucity of humoral autoreactivity to stress proteins in patients with systemic lupis erythematosus and rheumatoid arthritis argues against a direct role of anti-stress protein autoantibodies in the pathogenesis of these disorders.

John, M.C., Nedunchelliyan, S., Raghvan, N., 1991. Tuberculin testing in Indian elephants. Indian Journal of Veterinary Medicine 11, 48-49.

Turnbull, P.C., Bell, R.H., Saigawa, K., Munyenyembe, F.E., Mulenga, C.K., Makala, L.H., 1991. Anthrax in wildlife in the Luangwa Valley, Zambia. Veterinary Record 128, 399-403.
Abstract: An abnormally high mortality among hippos (Hippopotamus amphibius) in the Luangwa River valley between June and November 1987 and estimated to number more than 4000 deaths was attributed to anthrax. Several other species, particularly Cape buffalo (Syncerus caffer) and elephant (Loxodonta africana), appear to have been affected. A smaller outbreak of anthrax in hippos occurred between August and September 1988, approximately 100 km up-river. A field study was arranged in August 1989 to assess the extent of environmental contamination by Bacillus anthracis and the risks to people in the area, to study possible methods of control and to equip local laboratory staff for continued monitoring of the disease. The study confirmed the enzootic status of the region. The characteristics of the outbreaks of anthrax in 1987 and 1988, and the results of the field study are described

Vulfovich, Yu.V., 1991. Mycoplasm arthritogenicity and human mycoplasma-induced arthritis. Vestnik Adademii Meditsinskikh Nauk SSSR 1991, 6-9.

Wolfe, R., Cathey, M.A., Roberts, F.K., 1991. The latex test revisited. Arthritis and Rheumatism 34, 951-959.
Abstract: Rheumatoid factor (RF) testing by latex fixation in 8,287 outpatients yielded a sensitivity of 81.6% and 78.0% at titers of 1:20 and 1:80, respectively, and a specificity against noninflammatory rheumatic disorders (NIRD) of 96.6%  and 97.7% and against NIRD plus inflammatory disorders of 95.2% and 96.8%, respectively.  The predictive value of a positive test result at the clinic prevalence rate for rheumatoid arthritis (RA) (16.4%) was approximately 80%, and was 70% at 10% prevalence and 10% at 1% prevalence.  No associations of RA with age or sex were found in non-RA patients.  RF titers increased minimally with age in RA patients and were higher in men than in women.  This study suggests that latex testing is far more specific than has been believed and that the titer is not spuriously increased with age.

 1990. The story of Babe, the Asian elephant. Veterinary Viewpoints 2.

Breedveld, F.C., Dukmans, B.A.C., Mattie, H., 1990. Minocycline treatment for rheumatoid arthritis: An open dose finding study. Journal of Rheumatology 17, 43-46.

George, P.O., Rajan, A., Varkey, C.A., Balagopalan, T.P., Rajankutty, K., 1990. Osteo-arthritis in an elephant (Elephas maximus indicus). Journal of Veterinary and Animal Sciences 21, 157-159.

Haagsma, J., Eger, A. ELISA for diagnosis of tuberculosis and chemotherapy in zoo and wildlife animals. Proceedings of American Association of Zoo Veterinarians , 107-110. 1990.
Ref Type: Conference Proceeding
Abstract: The aim of this study was to improve the diagnosis of bovine tuberculosis in zoo and wildlife animals, in particular by using an Enzyme-Linked Immunosorbent Assay (ELISA). In addition, suspected cases of tuberculosis (TB) with a positive skin test and /or ELISA were treated with antituberculosis drugs. The diagnosis of TB in animals is based primarily on the intradermal tuberculin test, corresponding with cellular immune response. Although this test has practical disadvantages in zoo animals, the application is still of high value. For this purpose tuberculins with a well controlled high potency and specificity should be used. In order to diagnose hypergic or anergic animals it is recommended to use PPD tuberculin with double strength (2 mg tuberculoprotein per ml) or to double the dose (0.2 ml instead of 0.1 ml), so that about 10,000 I.U. are applied. A strict interpretation scheme can increase the efficacy of the test, in particular in the comparative test. In order to improve the diagnosis, we have studied for some years the use of the ELISA which corresponds with humoral immunity.

Koshy Varghese, Mammen Abraham, Valsala, K.V., Rajan, A., 1990. Osteoarthritis in an Indian elephant (Elephas maximus indicus). Cheiron 19, 185-186.

Mathew, E.S., Sulochana, S., Pillai, R.M., 1990. Isolation of Escherichia coli O109 from an Asian elephant (Elephas maximus indicus). Sri Lanka Veterinary Journal 37, 23-24.

Paulus, H.E., 1990. The use of combinations of disease-modifying antirheumatic agents in rheumatoid arthritis. Arthritis and Rheumatism 33, 113-120.

Sabin, J.E., 1990. Joseph Hersey Pratt's cost-effective class method and its contemporary application. Psychiatry 53, 169-184.

Schwartz, B.D., 1990. Infectious agents, immunity, and rheumatic diseases. Arthritis and Rheumatism 33, 457-465.

Gorina, L.G., Vulfovich, Yu.V., Zifyan, A.V., Bakovskaya, I.V., Pronin, A.V., Zheverzheeva, I.V., 1989. Human mycoplasmic arthritis and its pathogenetic mechanisms. Vestnik Adademii Meditsinskikh Nauk SSSR 1989, 84-87.

Kuntze, A., 1989. Dermatopathies in elephants and their treatment. Kleintierpraxis 34, 405-415.

Muller, M., Rytz, U. Dermatomycosis in two African elephants. Erkrankungen der Zootiere. Verhandlungsbericht des 31. Internationalen Symposiums uber die Erkrankungen der Zoo- und Wildtiere, Dortmund 1989.  207-209. 1989. Berlin, German Democratic Republic, Akademie Verlag.
Ref Type: Conference Proceeding
Abstract: Cases of dermatomycosis are reported in 2 adult African elephants in the Zoological Garden in Basle. Trichothecium, Scopulariopsis and Aspergillus spp. were isolated from skin biopsies.

Turnbull, P.C.B., Carman, J.A., Lindeque, P.M., Joubert, F., Hubschle, O.J.B., Snoeyenbos, G.H., 1989. Further progress in understanding anthrax in the Etosha National Park. [Namibia] Madoqua. 16, 93-104.
Abstract: Of 81 samples of water from pools, mud and soil collected from sites not connected with anthrax only one water sample contained Bacillus anthracis. The organism was isolated from 5 of 11 soil samples collected from sites where carcasses of animals known to have or suspected of having anthrax had lain. B. anthracis was also isolated from faeces of vultures and jackals, but not from 6 randomly collected bone samples. Six of 7 wildebeest, zebras and springbok found dying in the park were positive for anthrax. All of 7 lions tested had positive titres for anthrax, but 3 elephants, 2 zebra and 2 of 3 rhinos were negative (the other was thought to have been previously vaccinated). In laboratory tests vegetative forms of B. anthracis inoculated into water samples declined rapidly in number and the spores showed no sign of germination. It is suggested that water holes are not sites of germination and multiplication of B. anthracis.

Vulfovich, Yu.V., Gorina, L.G., Mitchenko, A.F., Goncharova, S.A., Gamova, N.A., Neustroeva, V.V., 1989. Mycoplasma and rheumatoid arthritis in children. Vestnik Adademii Meditsinskikh Nauk SSSR 1989, 82-84.

Wiegeshaus, E., Balasubramanian, V., Smith, D.W., 1989. Immunity to tuberculosis from the perspective of pathogenesis. Infect Immun 57 , 3671-3676.

Arnett, F.C., Edworthy, S.M., Bloch, D.A., McShane, D.J., Fries, J.F., Cooper, N.S., Healey, L.A., Kaplan, S.R., Liang, M.H., Luthra, H.S., Medsger, T.A., Jr., Mitchell, D.M., Neustadt, D.H., Pinals, R.S., Schalller, J.G., Sharp, J.T., Wilder, R.L., Hunder, G.O., 1988. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis and Rheumatism 31, 315-324.
Abstract: The revised criteria for the classification of rheumatoid arthritis (RA) were formulated from a computerized analysis of 262 contemporary, consecutively studied patients with RA and 262 control subjects with rheumatic diseases other than RA (non-RA). The new criteria are as follows: 1) morning stiffness in and around joints lasting at least 1 hour before maximal improvement; 2) soft tissue swelling (arthritis) of 3 or more joint areas observed by a physician; 3) swelling (arthritis) of the proximal interphalangeal, metacarpophalangeal, or wrist joints; 4) symmetric swelling (arthritis); 5) rheumatoid nodules; 6) the presence of rheumatoid factor; and 7) radiographic erosions and/or periarticular osteopenia in hand and/or wrist joints.  Criteria 1 and 4 must have been present for at least 6 weeks.  Rheumatoid arthritis is defined by the presence of 4 or more criteria, and no further qualifications (classic, definite or probable) or list of exclusions is required.  In addition, a "classification tree" schema is presented which performs equally well as the traditional (4 of 7) format.  The new criteria demonstrated 91-94% sensitivity and 89% specificity for RA when compared with non-RA rheumatic disease control subjects.

Chooi, K.F., Zahari, Z.Z., 1988. Salmonellosis in a captive Asian elephant. Journal of Zoo and Wildlife Medicine 19, 48-50.
Abstract: Salmonella blockley was isolated from an Asian elephant (Elephas maximus) with intestinal lesions in Malaysia.  A second elephant that died with similar lesions also was suspected to have Salmonella sp.  This is the first case of salmonellosis in an Asian elephant from Malaysia.

Clark, H.W., Coker-Vann, M.R., Bailey, J.S., Brown, T.M., 1988. Detection of mycoplasmal antigens in immune complexes from rheumatoid arthritis synovial fluids. Annals of Allergy 60, 394-398.
Abstract: This study was directed towards the detection of suspected antigenic microbial fragments in the immune complex (IC) fraction from chronic inflammatory disorders of the delayed type allergy. Mycoplasmas as the microbial prototype and joint fluid from the rheumatoid host were investigated. Protein-A affinity chromatography was used to isolate the immunoglobulin complex (IgG-IC) in six synovial fluids obtained from rheumatoid arthritis patients. The IgG-IC was digested with pepsin to further purify and obtain F(ab)2 complexes with greater specificity. The F(ab)2 complexes were dissociated and electrophoresed by SDS-PAGE and analyzed by immunoblotting using affinity purified rabbit antisera to six reference strains of human mycoplasmas. The presence of trace amount of mycoplasma antigens in the immune complex fractions was indicated by specific banding with antisera to M. pneumoniae, M. arthritidis, M. hominis, M. fermantans, and M. salivarium in one or more of the six synovial fluid fractions. The ELISA and immunoblot assays of seroconversion in rabbits immunized with the synovial fluid fractions also indicated the presence of mycoplasmal antigens.

Thoen, C.O., 1988. Tuberculosis. Journal of the American Veterinary Medical Association 193, 1045-1048.

Bennet, D., 1987. Immune-based erosive inflammatory joint disease of the dog: canine rheumatoid arthritis. I. Clinical, radiological and laboratory investigations. Journal of Small Animal Practice 28, 779-797.
Abstract: The features of 30 cases of canine rheumatoid arthritis are described.  The disease is a chronic symmetrical polyarthritis characterized by erosive, destructive changes within the joint.  The latter can be identified on radiographs by loss of mineral, the presence of discrete erosions or an irregular joint margin.  Increased periarticular soft tissue is common and periosteal new bone is not unusual.  The most obvious clinical feature is generalized stiffness particularly after rest.  Joints are often thickened and painful on manipulation. a third of cases present with pyrexia, lethargy and inappetence in addition to lameness.  Synovial fluid evaluation shows an increased number of white cells, most of which are polymorphs; the mucin clot is poor.  The ESR is generally increased and rheumatoid factor (an antiglobulin auto-antibody) is present in 73 per cent of cases.  Treatment is often unrewarding, although many dogs can cope for considerable periods of time.

Taylor-Robinson, D., Furr, P.M., Tully, J.G., Barile, M.F., Moller, B.R., 1987. Animal models of Mycoplasma genitalium urogenital infections. Israel Journal of Medical Sciences 23, 561-564.
Abstract: Male and female animals were inoculated urogenitally with Mycoplasma genitalium, recovered originally from men with nongonococcal urethritis.  Mice, hamsters and male rhesus monkeys (Macaca mulatta) were resistant.  Male cynomolgus monkeys (Macaca fascicularis) were not as sensitive as male chimpanzees (Pan troglodytes): 9 of 11 developed an obvious genital tract infection, some shedding organisms for more than 18 weeks.  M. genitalium was recovered from the blood of two of them when large numbers of organisms were in the urethra. Most of the chimpanzees colonized with the organisms had increased numbers of polymorphonuclear leukocytes in the genital tract and developed a fourfold or greater antibody response. Female squirrel monkeys (Saimiri sciureus) and female tamarins (Saguinus mystar) exhibited low-level genital tract infections following intravaginal inoculation, whereas marmosets (Callithrix jacchus) and chimpanzees developed prolonged infections after similar inoculation: thus, female chimpanzees shed organisms for 12 to 15 weeks.  Marmosets and grivet monkeys (Ceropithecus aethiops) developed salpingitis with antibody responses after intraoviduct inoculation, and baboons (Papio anubis) developed parametritis after intracervical inoculation.  The results offer substantial evidence for the pathogenicity of M. genitalium for the urogenital tract of subhuman primates, and suggest that the microorganism may have a role in human genital tract infections.

 1986. New species of bacteria in the genus Kurthia--Kurthia sibirica sp. nov. Mikrobiologiia 55, 831-835.
Abstract: Six aerobic gram-positive nonspore-forming bacterial strains belonging to the Kurthia genus were isolated from the Magadan (Susuman) mammoth found in the permafrost of the East Siberia. The strains are a phenotypically homogeneous group different from the two known species (K. zopfii and K. gibsonii) in requiring more vitamins, the absence of growth in a medium with 7% NaCl, and a low level of DNA-DNA hybridization (not more than 45%). Moreover, the strains differ from K. zopfii in the synthesis of a yellow pigment, the activity of phosphatase, and the absence of coccoid forms; the bacteria differ from K. gibsonii in the absence of growth at a temperature above 40 degrees C. The organisms are referred to as Kurthia sibirica sp. nov. The type strain 13-2 has been deposited in the All-Union Collection of Microorganisms as strain VKB B-1549.

Arora, B.M. Tuberculosis in wildlife in India. Summer Institute on Health, Production and Management in Wildlife.  67-78. 1986. India, Indian Veterinary Institute.
Ref Type: Conference Proceeding

Phillips, P.E., 1986. Infectious agents in the pathogenesis of rheumatoid arthritis. Seminars in Arthritis and Rheumatism 16, 1-10.

Barile, M.F., Kapatais-Zoumbos, K., Grabowski, M.W., Snoy, P., Sneller, M., Plotz, P., Gill, V., Chandler, D.K.F. Mycoplasma hominis septic arthritis: Naturally occurring in humans and experimentally induced in chimpanzees. Abstracts of the Annual Meeting of the American Society for Microbiology , 95. 1985.
Ref Type: Abstract
Abstract: A recurrent septic arthritis developed in the wrist and prosthetic knee of a patient and continues to persist after ten months.  Aspirations were negative for bacteria and viruses but consistently grew out pure cultures of M. hominis.  The first positive culture was obtained 35 days after admission and four additional aspirations contained 10⁴ to 10⁷ CCU/ml of M. hominis.  Oxytetracycline was initiated on Day 41 and by Day 65 the aspiration was negative.  Treatment was continued for 6 months and terminated because of severe adverse gastrointestinal disturbances.  After treatment was discontinued the patient suffered a relapse, and M. hominis was isolated again. Experimental arthritis was induced by inoculating synovial fluids containing 10^4 CCU/ml of M. hominis into the knee of a chimpanzee.  Two additional chimpanzees inoculated with a pure culture of M. hominis containing 10^6 and 10^7 CCU/ml also developed arthritis.  Sera and synovial fluids from the patient and chimpanzee contained MI specific antibody to M. hominis. The septic arthritis induced in the chimpanzee was remarkably similar to disease in the patient.

Clark, H.W., Bailey, J.S., Brown, T.M., 1985. Medium-dependent Properties of Mycoplasmas. Diagn Microbiol Infect Dis 3, 283-294.
Abstract: Without a cell wall, the morphology, growth rate, and composition of mycoplasmas are culture media-dependent with variable properties best described as environmentally related. The adaptation of mycoplasmas to either a tissue cell or cell-free culture media, with dependency upon specific animal or plant products for survival, has led to investigations of their human host-related properties. The influence of culture media on the antibiotic sensitivities of mycoplasmas was measured by use of three different broths in two different assay systems. The variable results indicate that the inhibition of mycoplasma protein synthesis or growth may also by host-tissue dependent. The addition of noninhibitory penicillins to different culture media was found to affect the composition and antigenicity of some mycoplasmas. Using the complement fixation test, we found some human sera that were more reactive than rabbit antisera to mycoplasmas cultured in human synovial broth or in myelin-enriched broth. Mycoplasmas cultured in human lung broth and pig lung broth had media-dependent antigenicity. The antigenicity and the growth of mycoplasmas were found to depend on the proteolytic enzymes used to provide the essential peptides in tissue broths. The media-affected mycoplasmas indicate the presence of species-, strain-, and tissue-specific antigen sites that may determine immunopathogenicity in the genetically susceptible host.

Cole, B.C., Washburn, L.R., Taylor-Robinson, D., 1985. Mycoplasma-induced arthritis. In: Razin, S., Barile, M.F. (Eds.), The Mycoplasmas. Volume IV. Mycoplasma pathogenicity. Academic Press, New York, pp. 107-160.

Raphael, B.L., Clubb, F.J., 1985. Atypical salmonellosis in an African elephant. Proceedings American Association of Zoo Veterinarians 57.

Snoy, P.J., Kapatais-Zoumbos, K., Grabowski, M.W., Chandler, D.K., Barile, M.F. Chimpanzee (Pan troglodytes) as a model for a human Mycoplasma arthritis. Laboratory Animal Science 35, 533. 1985.
Ref Type: Abstract
Abstract: Various Mycoplasma species have been shown to cause arthritis in animals and have been isolated from patients with septic arthritis and Reiter's syndrome.  In this study, Mycoplasma hominis was isolated from synovial fluid of a patient with septic arthritis and then inoculated into the knee joints of several chimpanzees.  The resulting arthritis in the chimpanzees was similar clinically to the arthritis in the patient.  The course of disease in the chimpanzee was monitored by sequential biopsies of the joint capsule, clinical signs, and analysis of synovial fluid for volume, leukocyte count, M. hominis titer and antibody response.  Different titers of Mycoplasma were inoculated in chimpanzees and a dose response was established.  Sequential biopsies revealed and acute progressive but transient synovitis with a corresponding elevation in the amount of synovial fluids, synovial leukocyte counts, colonization by M. hominis and an increased antibody response.  These data demonstrate that the chimpanzee provides an excellent model for the study of Mycoplasma induced arthritis in man.

Allen, J.L., Welsch, B., Jacobson, E.R., Turner, T.A., Tabeling, H., 1984. Medical and surgical management of a fractured tusk in an African elephant. Journal of the American Veterinary Medical Association 185, 1447-1449.

Janssen, D.L., Karesh, W.B., Cosgrove, G.E., Oosterhuis, J.E., 1984. Salmonellosis in a herd of captive elephants. Journal of the American Veterinary Medical Association 185, 1450-1451.

Mustafa, A.H., 1984. Isolation of anthrax bacillus from an elephant in Bangladesh. Veterinary Record 114, 590.

Scott, W.A., 1984. Salmonellosis in an African elephant. Veterinary Record 115, 391.

Snider, D.E., Jr., Jones, W.D., 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

Devine, J.E., Boever, W.J., Miller, E., 1983. Isoniazid therapy in an Asiatic elephant (Elephas maximus). Journal of Zoo and Wildlife Medicine 14, 130-133.

McGavin, M.D., Walker, R.D., Schroeder, E.C., Patton, C.S., McCracken, M.D., 1983. Death of an African elephant from probable toxemia attributed to chronic pulpitis. Journal of the American Veterinary Medical Association 183, 1269-1273.
Abstract:  A 31-year-old captive male African elephant (Loxodonta africana) of 5,000-kg body weight died suddenly in ventral recumbency.  Lesions seen at necropsy were bilateral purulent pulpitis and periodontitis of both tusks, serous atrophy of coronary groove fat, Grammocephalus cholangitis, myocardial and skeletal lipofuscinosis, and scattered segmental necrosis in the pectoral muscles.  Nonhemolytic streptococci, Corynebacterium sp, Pertostreptococcus anaerobius, Fusobacterium nucleatum, and Bacteroides sp were recovered from the exudate around one or both tusks.  We postulated that the elephant died of hypoxia from prolonged ventral recumbency because of weakness and inability to rise secondary to toxemia from bilateral pulpitis and periodontitis.

Saunders, G., 1983. Pulmonary Mycobacterium tuberculosis infection in a circus elephant. Journal of the American Veterinary Medical Association 183, 1311-1312.

Schmidt, M.J., 1983. Antagonism of xylazine sedation by yohimbine and 4-aminopyridine in an adult Asian elephant (Elephas maximus). Journal of Zoo and Wildlife Medicine 14, 94-97.
Abstract: Heavy xylazine sedation was successfully antagonized by intravenous injection of yohimbine and 4-aminopyridine (4-AP) in an adult female Asian elephant (Elephas maximus) prior to euthanasia.  A total xylazine dose of 1,200 mg intramuscularly plus 600 mg intravenously (approximately 0.33 mg/kg body weight) was given resulting in heavy sedation.  After 50 minutes of deep recumbent sedation, 425 mg yohimbine and 1,000 mg of 4-AP were administered intravenously.  Xylazine sedation was antagonized and the elephant was up and walking around within 5 minutes of antagonist administration.  The elephant remained standing for other 3 hours; at which point euthanasia was performed. Comment: Report concerns animal with arthritis and chronic foot problems.

Wallach, J.D., Boever, W.J., 1983. Perissodactyla (equids, tapirs, rhinos), Proboscidae (elephants), and Hippopotamidae (hippopotamus). In: Wallach, J.D., Boever, W.J. (Eds.), Diseases of exotic animals. W.B. Saunders Company, Philadelphia, pp. 761-829.

Wallach, J.D., Boever, W.J., 1983. Tuberculosis. Diseases of Exotic Animals. pp. 791-792.

Boyce, L., Sayer, P., Inima, A.A., 1982. Fatal enteritis in a repatriated African elephant. Proceedings American Association of Zoo Veterinarians 75-76.

Brown, T.M., Bailey, J.S., Iden, K.I., Clark, H.W., 1982. Antimycoplasma approach to the mechanism and the control of rheumatoid disease. In: Sorenson, J.R.J. (Ed.), Inflammatory diseases and copper. Humana Press, pp. 391-407.

Jones, W.D., Jr., Good, R.C., 1982. Hazel elephant redux (letter). Am. Rev. Respir. Dis. 125, 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.

Wickremasuriya, U.G.J.S., Kenderagama, K.W.T., 1982. A case report of haemorrhagic septicaemia in a wild elephant. S. L. vet. J, 30, 24.

Woodford, M.H., 1982. Tuberculosis in wildlife in the Ruwenzori National Park, Uganda (Part II). Trop. Anim. Hlth. Prod. 14, 155-160.
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.

Choquette, L.P.E., Broughton, E., 1981. Anthrax. In: Davis, J.W., Karstad, L.H., Trainer, D.O. (Eds.), Infectious diseases of wild mammals. The Iowa State University Press, Ames, Iowa.

Clark, H.W., Laughlin, D.C., Brown, T.M., 1981. Rheumatoid arthritis in elephants -- a review to date. Proceedings American Association of Zoo Veterinarians 95-99.

Greenberg, H.B., Jung, R.C., Gutter, A.E., 1981. Hazel Elephant is dead (of tuberculosis) (letter). Am. Rev. Respir. Dis. 124, 341.
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 animals.

Gutter, A. Mycobacterium tuberculosis in an Asian elephant. Proc.Am.Assoc.Zoo Vet.  105-106. 1981.
Ref Type: Conference Proceeding

Hoff, G.L., Trainer, D.O., 1981. Hemorrhagic diseases of wild ruminants. In: Davis, J.W., Karstad, L.H., Trainer, D.O. (Eds.), Infectious diseases of wild mammals. The Iowa State University Press, Ames, Iowa.

Mann, P.C., Bush, M., Janssen, D.L., Frank, E.S., Montali, R.J., 1981. Clinicopathologic correlations of tuberculosis in large zoo mammals. Journal of the American Veterinary Medical Association 179, 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.

McGavin, M.D., Schroeder, E.C., Walker, R.D., McCracken, M.D., 1981. Fatal aspiration pneumonia in an African elephant. Journal of the American Veterinary Medical Association 179, 1249-1250.

Rosen, M.N., 1981. Pasteurellosis. In: Davis, J.W., Karstad, L.H., Trainer, D.O. (Eds.), Infectious diseases of wild mammals. The Iowa State University Press, Ames, Iowa.

Thoen, C.O., Himes, E.M., 1981. Tuberculosis. In: Davis, J.W., Karstad, L.H., Trainer, D.O. (Eds.), Infectious diseases of wild mammals. The University of Iowa Press, Ames, Iowa.

Brown, T.M., Clark, H.W., Bailey, J.S., 1980. Rheumatoid arthritis in the gorilla: A study of mycoplasma-host interaction in pathogenesis and treatment. Proceedings of the Symposium on the Comparative Pathology of Zoo Animals. Smithsonian Institution, Washington,D.C., pp. 259-265.
Abstract: Rheumatoid arthritis in a gorilla was first observed at the National Zoo in 1969.  As the result of our preliminary report, several other gorillas were recognized to have similar symptoms.  These true animal models have been observed for seven to nine years with highly successful therapeutic results based upon a pathogenetic concept developed over a 30-year period in a study of the disease in humans.  The seriousness of arthritis in the gorilla is reflected by the reports we have received in the past few years of a total of 26 additional captive gorillas variously affected.  The systemic aspects of rheumatoid arthritis, such as failure to gain weight and grow normally, hot and swollen joints, migratory arthritis, severe localized muscular atrophy, generalized weakness and depression, presented classical evidence of the rheumatoid disease pattern.  Remission occurred in one pregnant gorilla, and a flare reaction followed delivery, which is characteristic of the disease pattern in the human counterpart.      Laboratory studies were in support of rheumatoid disease. Immunoglobulin alterations were noted with reversed A/G ratios and elevations of IgC and IgM.  Positive bentonite flocculation rheumatoid factor tests were observed, and a positive lupus erythematosus (LE) test was noted in one animal.  Abnormal hematologic findings were frequent, with increased sedimentation rates and lymphocytosis.      Evidence of mycoplasma association was indicated by complement-fixing antibody response, positive cultures, and demonstration of the mycoplasma antigen in the tissue.  Of greatest significance were the induced rise and subsequent fall of mycoplasma antibodies resulting from the challenge to the host with antimycoplasma medication and the production of the Jarisch-Herxheimer flare response.  All these mycoplasma relationships have been found in man with the additional demonstration of delayed-type skin reaction with mycoplasma antigen.      It has been stressed that in infectious hypersensitivity, the microbial source is obscured, yet it must be defined and the proper therapy planned on an individualized basis.  The medication must be given in relatively small, intermittent dosage to avoid the development of delayed hypersensitivity which negates the drug effect.  Until more effective medications are developed, the treatment must also be administered over an extended period of time to achieve permanent control of the disease.  The demonstration of the importance of the pathogenesis concept speaks for itself in the final analysis with the recovery of severely disabled gorillas.      In conclusion, it would appear that a study of rheumatoid arthritis in the gorilla and man, approached from the point of view of comparative pathology and medicine, has opened a new direction for an understanding of the pathogenesis of this complex disease.  From these studies, one can now visualize for the first time that rheumatoid arthritis in the gorilla and in man is a controllable and potentially curable disease.  It seems that new thinking in regard to further demonstrations of etiologic associations must be given to all species where tissue hypersensitivity to microbial agents is basic.  It is suggested that Koch's postulates were not designed to include this area of pathogenesis where the role of the host is as significant as that of the parasite--an omission which has delayed the development of new knowledge in this area for a half a century. Is not the time at hand to revise our concepts and move in a new direction?

Clark, H.W., Laughlin, D.C., Bailey, J.S., Brown, T.M., 1980. Mycoplasma species and arthritis in captive elephants. Journal of Zoo and Wildlife Medicine 11, 3-15.
Abstract: Sixty-seven elephants (62 Elephas maximus and 5 Loxodonta africana) from three circus groups and five zoos were examined serologically and cultured for mycoplasma in a search for arthritogenic agents previously unrecognized in this animal species.  In two groups of elephants, 28 of the 35 female genital tracts cultured were found to be colonized by one or more strains of mycoplasma.  More than half of the elephants had complement fixing antibodies to one or more of the new mycoplasma isolates.  Lameness and other rheumatoid disorders were found associated with rheumatoid factor activity and changes in mycoplasma antibody titers.  In view of the arthritogenic activity of mycoplasma in other species, these new findings suggested the clinical significant of mycoplasma in elephants and the need for investigation, especially in relation to the high incidence of rheumatoid-type disorders observed in these captive elephants.

Thoen, C.O., Himes, E.M., 1980. Mycobacterial infections in exotic animals. In: Montali, R.J., Migaki, G. (Eds.), The comparative pathology of zoo animals. Smithsonian Institution Press, Washington,D.C., 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.

Thoen, C.O., Mills, K., 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, 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 ELISA.

 1979. "Motty" -- Birth of an African/Asian elephant at Chester Zoo. Elephant 1, 36-40.

Chandrasekharan, K. Common diseases of elephants. State Level Workshop on Elephants.  51-61. 1979. India, College of Veterinary and Animal Sicences, Kerala Agricultural University.
Ref Type: Conference Proceeding

Clark, H.W., Laughlin, D.C., Bailey, J.S., Brown, T.M., 1979. Isolation of mycoplasma from the genital tracts of elephants. Elephant 1(3), 9-10.

Cole, B.C., Cassell, G.H., 1979. Mycoplasma infections as models of chronic joint inflammation. Arthritis and Rheumatism 22, 1375-1381.

Garlt, C., Kiupel, H., Ehrentraut, W., 1979. Botulism in elephants. Erkrankungen der Zootiere 13, 207-211.

Gordon, D.H., Isaacson, M., Isaacson, M., 1979. Plague antibody in large African mammals. Infect Immun 26, 767-769.
Abstract: Plague hemagglutinating antibodies to a titer of 1:1,024 were demonstrated in 6.6% of buffalo and 0.3% of elephant sera tested 1 year after a plague epidemic in the same area.

Upadhya, A.S., Krishnappa, G., Ahmed, S.N., Keshavamurthy, B.S., 1979. Serological evidence of leptospiral antibodies in elephants. Current Science 48, 733.

Wilkes, E., Meek, E.S., 1979. Rheumatoid arthritis: Review of searches for an infectious cause. Part II. Infection 7, 192-197.

Wilkes, E., Meek, E.S., 1979. Rheumatoid arthritis: Review of searches for an infectious cause. Part I. Infection 7, 125-128.
Abstract: No distinctive pattern has yet emerged from the acumulated mass of results that would provide a generally acceptable hypothesis of the etiology of rheumatoid arthritis. A number of immunologic aberrations have been described, but there has been no identification of a key immunologic defect that might link together the various components of the immune response into an agreed pattern.  The possiblity of a persistent antigenic stimulus arising from an infection cannot be confirmed or refuted.  If a virus is involved, it would seem more likely to be a "slow" virus rather than a commonly recognized form, but there is no strong candidate of this type in view.  Despite the fact that mycoplasmas are undoubtedly arthritogenic in other species, their role as an atiologic agent in rheumatoid arthritis has not been proven.  The idea that bacterial cell wall peptidoglycan may provide a persistent stimulus has much to offer, but it is not possible at this stage to accept peptidoglycan as a recognized etiologic factor.  This suggestion will, however, undoubtedly stimulate much further investigation.

Brown, T.M., Clark, H.W., 1978. Rheumatoid inflammation -- Part I. Inflo (Arthritis Institute) 11, 1-2.

Clark, H.W., Bailey, J.S., Laughlin, D.C., Brown, T.M., 1978. Isolation of mycoplasma from the genital tracts of elephants. Zentralblatt fur Bakteriologie,Parasitenkunde,Infektionskrankheiten und Hygiene 1. Abt. Originale 241, 262.

Thoen, C.O., Richards, W.D., Jarnagin, J.L., 1977. Mycobacteria isolated from exotic animals. Journal of the American Veterinary Medical Association 170, 987-990.

Alexander, J.W., Begg, S., Dueland, R., Schultz, R.D., 1976. Rheumatoid arthritis in the dog: clinical diagnosis and management. Journal of the American Animal Hospital Association 12, 727-734.

Clark, H.W., Bailey, J.S., Brown, T.M. Mycoplasma hypersensitivity reactions. Proceedings of the Society for General Microbiology 111, 171. 1976.
Ref Type: Abstract
Abstract: Many immunological disorders that apparently are cell-mediated have no known aetiologic antigens other than tissue-related autoantibodies.  The human host is challenged continually by many microbial antigens including several types of mycoplasmas.  The immunologic response to mycoplasma antigens is dependent upon several factors other than colonizability and cytopathogenicity.  Mixed microbial infections can have an augmentive or suppressive effect on the human host cell-mediated immunity (CMI).  Mycoplasma can stimulate the thymus-derived 'T' cells and the bone marrow 'B' cell systems as indicated by various CMI responses such as the migratory inhibitory factor, delayed-type skin reactions, lymphocyte transformations, and humoral antibody reactions in the human host.      Investigations of the mycoplasma hypersensitivity reactions in chronic rheumatoid disorders have included several factors such as long-term monitoring of CMI responses and obscured foci of mycoplasma antigens that would distinguish them from the acute-convalescent responses.  In addition to the effects of therapeutic agents (immunosuppressants), physiological changes (hormonal), and environmental factors (trauma) on CMI, the 'T' cell derived anti-IgG rheumatoid factor can neutralize the humoral mycoplasma antibodies.  Recent studies indicate that the frequent and variable anergic responses observed in rheumatoid disorders are dependent upon both the test mitogen and the mycoplasma antigen as well as the host lymphocytes. Tissue inflammation resulting from antigen-antibody hypersensitivity reactions, apparently occurs when the CMI responsive host is challenged by mycoplasma reinfection or antigen released from a tissue focus.  The incorporation of specific tissue antigens by mycoplasma is another factor influencing their reactions in systemic "autoimmune" disorders and may require the challenging antigenic precursors to be cultured in specific human tissue media.  The identification of the sensitizing and challenging antigens also includes the appraisal of mycoplasma exoantigens and exoenzymes, such as DNase, released into the tissues as well as the physiologically optimum fractions.

Newton, C.D., Lipowitz, A.J., Halliwell, R.E., Allen, H.L., Biery, D.N., Schumacher, H.R., 1976. Rheumatoid arthritis in dogs. Journal of the American Veterinary Medical Association 168, 113-121.

Pedersen, N.C., Pool, R.C., Castles, J.J., Weisner, K., 1976. Noninfectious canine arthritis: rheumatoid arthritis. Journal of the American Veterinary Medical Association 169, 295-303.
Abstract: Chronic unremitting, generally symmetric, erosive arthritis was studied in 8 dogs.  The disease had clinical, serologic, radiographic, and pathologic changes similar to those of rheumatoid arthritis of man.  The condition occurred mainly in smaller breeds of dogs, with time of onset from 8 months to 8 years of age.  Characteristic radiographic changes were seen in the first several weeks to several months after the appearance of the initial lameness.  Synovial fluid contained an increased number of neutrophils, and synovial fluid and synovial tissues were sterile for anaerobic and aerobic bacteria, mycoplasma, chlamydia, and viruses.  Corticosteroids were therapeutically ineffective in all of the cases; however, corticosteroids, cyclophosphamide and azathioprine were effective when used in combination in several dogs.

Windsor, R.S., Scott, W.A., 1976. Fascioliasis and salmonellosis in African elephants in captivity. British Veterinary Journal 132, 313-317.

Burke, T.J., 1975. Probable tetanus in an Asian elephant. Journal of Zoo and Wildlife Medicine 6, 22-24.

Ebedes, H., 1975. Anthrax epizootics in wildlife in Etosha National Park, South West Africa. In: Page, L.A. (Ed.), Wildlife Diseases. Plenum Press, New York, pp. 519-526.

Newton, C.D., Lipowitz, A.J., 1975. Canine rheumatoid arthritis: A brief review. Journal of the American Animal Hospital Association 11, 595-599.

von Benten, K., Fiedler, H.H., Schmidt, U., Schultz, L.C., Hahn, G., 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 82, 316-318.

Brown, T.M., Clark, H.W., Bailey, J.S., 1974. Natural occurance of rheumatoid arthritis in great apes -- a new animal model. Proceedings of the Zoological Society of the Philadelphia Centennial Symposium on Science and Research 43-79.

Decker, R.A., Krohn, A.F., 1973. Cholelithiasis in an Indian elephant. Journal of the American Veterinary Medical Association 163, 546-547.
Abstract: Cholelithiasis with accompanying dilation of the bile ducts was found on necropsy on a young Indian elephant ( Elephas maximus).  Salmonella london was isolated from a composite of minced intestine, liver, spleen and heart.

Pinto, M.R.M., Jainudeen, M.R., Panabokke, R.G., 1973. Tuberculosis in a domesticated Asiatic elephant Elephas maximus. Veterinary Record 93, 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.

Sokoloff, L., 1973. Animal model of human disease: rheumatoid arthritis.  Animal model: arthritis due to Mycoplasma in rats and swine. American Journal of Pathology 73, 261-264.

Sokoloff, J., 1972. The pathology of rhematoid arthritis and allied disoders. In: Hollander, J.L., McCarty, D.J. (Eds.), Arthritis and Allied Conditions. Lea and Febiger, Philadelphia,PA, pp. 309-332.

Vaughan, J.H., 1972. The rheumatoid factors. In: Hollander, J.L., McCarty, D.J. (Eds.), Arthritis and Allied Conditions. Lea and Febiger, Philadelphia,PA, pp. 153-171.

Weissmann, G., 1972. Lysosomal mechanisms of tissue injury in arthritis. Seminars in Medicine of the Beth Israel Hospital, Boston 286, 141-146.

Windsor, R.S., Ashford, W.A., 1972. Salmonella infection in the African elephant and black rhinoceros. Trop. Anim. Hlth. Prod. 4, 214-219.
Abstract: Salmonellosis in two captive African elephants and a black rhinoceros is described.  Necropsy findings and characteristics of the salmonellae isolated are outlined. Possible sources of infection are discussed and on the basis of their findings, the authors make recommendations for the care of newly captured wild animals.

Prescott, C.W., 1971. Blackleg in an elephant. Veterinary Record 88, 598-599.

Brown, T.M., Clark, H.W., Bailey, J.S., Gray, C.W., 1970. A mechanistic approach to treatment of rheumatoid type arthritis naturally occuring in a gorilla. Trans. Am. Clin. and Climat. Assoc. 82, 227-247.

Ruddy, S., Austen, K.F., 1970. The complement system in rheumatoid synovitis. Arthritis and Rheumatism 13, 713-723.
Abstract: Stoichiometric hemolytic assays were used to measure the activities of the first four reacting components of the complement sequence in synovial fluids from patients with seropositive or seronegative rheumatoid arthritis or degenerative joint disease.  The pattern of component reductions in the seropositive rheumatoid arthritis fluids was consistent with activation of the complement system by an intra-articular immunologic process.

Bartfield, H., 1969. Distribution of rheumatoid factor in non-rheumatoid states. Annals of the New York Academy of Science 168, 30-40.

Gorovitz, C., 1969. Tuberculosis in an African elephant. American Association of Zoo Veterinarians Newsletter January 20.

Mongan, E.S., Atwater, E.C., 1968. A comparison of patients with seropositive and seronegative rheumatoid arthritis. Medical Clinics of North American 52, 533-538.

Ratnesar, P., 1966. Can elephants transmit disease to man? Journal of Tropical Medicine and Hygiene 69, 215-216.

Seneviratna, P., Wettimuny, S.G., 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.

De Alwis, M., Thanbithurai, V., 1965. Hemorrhagic septicemia in a wild elephant in Ceylon. Ceylon Veterinary Journal 13, 17-19.

Sastry, G.A., 1964. Anthrax in civet cat and an elephant. Indian Veterinary Journal 41, 376.

Gopalan, S., 1962. Elephants - Their Capture, Care and Management. The Manager, Publications, Government of India Press, Delhi. 8., Delhi.
Abstract: Note: Dr. S. Chandrasekharam Pillai's notes revised by Dr. S. Gopalan of Madras Forestry Dept.

Gorovitz, C., 1962. Tuberculosis in an African elephant. Nord Vet Med 14, 351-352.

McGaughey, C.A., 1962. Diseases of elephants. Part 4. Ceylon Veterinary Journal 10, 3-9.

McGaughey, C.A., 1961. Diseases of elephants.  Part 3. Ceylon Veterinary Journal 9, 94-98.

McGaughey, C.A., 1961. Diseases of elephants. Part 2. Ceylon Veterinary Journal 9, 41-48.

Mellors, R.C., Nowoslowski, A., Korngold, L., Sengson, B.L., 1961. Rheumatoid factor and the pathogenesis of rheumatoid arthritis. Journal of Experimental Medicine 113, 475-483.

Mellors, R.C., Nowoslowski, A., Korngold, L., 1961. Rheumatoid arthritis and the cellular origin of rheumatoid factors. American Journal of Pathology 39, 533-546.

Pienaar, U.d.V., 1961. A second outbreak of anthrax among game animals in the Kruger National Park, 5th June to 11th October, 1960. Koedoe 4, 4-16.

Ropes, M.W., 1959. Diagnostic criteria for rheumatoid arthritis: 1958 revision. Annals of the Rheumatic Diseases 18, 49-53.

Holmes, T.H., 1956. Multidiscipline studies of tuberculosis. In: Sparer, P.J. (Ed.), Personality,stress, and tuberculosis. Int. Univ. Press, New York, pp. 65-125.

Selye, H., 1956. Recent progress in stress research, with reference to tuberculosis. In: Sparer, P.J. (Ed.), Personality, stress, and tuberculosis. Int. Univ. Press, New York, pp. 45-64.

Halloran, P.O., 1955. A bibliography of references to diseases in wild mammals and birds. American Journal of Veterinary Research 16(part 2), 161.

McGaughey, C.A., Schmid, E.E., St.George, C., Velaudapillai, T., 1954. Salmonella infections of domesticated and wild animals in Ceylon. Ceylon Veterinary Journal 2, 86-88.

Heyman, A., Sheldon, W.H., Evans, L.D., 1953. Pathogenesis of the Jarisch-Herxheimer reaction. British Journal of Venereal Diseases 28 , 50.

McGaughey, C.A., Schmid, E.E., Velaudapillai, T., Weinman, A.N., 1953. Salmonella typhimurium in young elephants and chimpanzees. Veterinary Record 65, 431-432.

Sailer, O., 1951. Report on calf diphtheria in elephants. Zoologische Garten 18, 103.

Goss, L.J., 1950. Animal hospital. 55th Annaul Report,New York Zoological Society 20-23.

Brown, T.M., Wichelhausen, R.H., Robinson, L.B., Merchout, W.R., 1949. The in vivo action of aureomycin on pleuropneumonia-like organisms associated with various rheumatic diseases. Journal of Laboratory and Clinical Medicine 34, 1404-1410.

Buttiauz, R., Gaumont, R., 1948. Infection mortelle d'un elephant par Salmonella oslo. Bull. Acad. Vet. Fr. 21, 399-342.

Ferrier, A.J., 1947. The care and management of elephants in Burma. Steel Brothers, London.

Seidemann, R.M., Wheeler, H.M., 1947. Human anthrax from elephant's tusks. Journal of the American Veterinary Medical Association 135, 837.

Curasson, G., 1942. Traite de pathologie exotique veterinaire et comparee. Vigot Freres, Paris.

Goss, L.J., 1942. Diagnosis and treatment of diseases of wild animals in captivity. The Cornell Veterinarian 32, 155-161.

Goss, L.J., 1942. Tetanus in an elephant (Elephas maximus). Zoologica 27, 5-6.

Matzke, M., 1940. Enteritis (Breslau) infektion dei elefanten. Tierarztl. Rdsch. 46, 521-522.

Pfaff, G., 1940. Diseases of Elephants. Superintendent, Govt. Printing and Stationary, Burma, Rangoon.

Sabin, A.B., Warren, J., 1940. The curative effect of certain gold compounds on experimental proliferative chronic arthritis in mice. Journal of Bacteriology 40, 823-856.

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.

Hammer, A., 1939. Ueber Hautleiden und aussere Leiden de Elefanten. Berl. Munch. Tierarztl. Wochenschr. 2, 293-344.

Urbain, A., 1938. Tuberculosis in wild animals in captivity. Annales de L'Institute Pasteur 61, 705-730.

Winogradradsky, S., 1938. La microbiologie ecologique ses principes - son procede. Annales de L'Institute Pasteur 64, 715-730.

Iyer, A.K., 1937. Veterinary science in India, ancient and modern with special reference to tuberculosis. Agric. Livest. India 7, 718-724.

Curasson, G., 1936. Treatise on the pathology of exotic animals. Vigot Freres, Paris.

Datta, S.C.A., 1934. Report of the pathology section. Ann. Rep. Imp. Inst. Vet. Research Muktesar 25-33.

Mudaliar, G.K., 1934. Milzbrandepidemie unter elefanten. Indian Veterinary Journal 11, 1.

Noback, C.V., 1934. Report of the veterinarian. 38th Annaul Report,New York Zoological Society.

Verge, J., Thierz, P., 1934. Sur un streptocoquie isolee de l'elephant. C. R. Soc. Biol. , Paris 115, 1488-1489.
Abstract: .

Verge, J., Placidi, L., 1934. La fieve charbonneuse chez les animaux de menagerie. C. R. Soc. Biol. , Paris 116, 718.

Russeff, C., 1932. Milzbrand beim elefanten. Deutsche Tierarztliche Wochenschrift 40, 276.

Baldrey, F.S.H., 1930. Tuberculosis in an elephant. J. R. Army Vet. Corp. 1, 252.

Bopayya, A.B., 1928. Tuberculosis in an elephant. Indian Veterinary Journal 5, 142-145.

Gupta, V., 1928. Anthrax epidemic in the Minbyin reserve. Indian Veterinary Journal 4, 216-228.

Scott, H.H., 1927. Report on the deaths occurring in the society's gardens during the year 1926. Procedings of the Zoological Society of London 1927, 173-198.

Narayanan, R.S., 1925. A case of tuberculosis in an elephant. Journal of Comparative Pathology 38, 96-97.

Ishigami, T., 1918. The influence of psychic acts on the progress of pulmonary tuberculosis. Am. Rev. Tuberc. 2, 470-484.

Satyendra, N.M., 1914. Sur une forme particuliere de pasteurellose chez un elephant indian. Zentralblatt fur Bakteriologie,Parasitenkunde,Infektionskrankheiten und Hygiene 1. Abt. Originale 73, 12.

Howard, G., 1913. Charbon chez l'elephant. Veterinary Record 26, 69-71.

Howard, G.G., 1913. Anthrax in elephants. Veterinary Record 26, 69-71.

Thieringer, H., 1911. About tuberculosis in an elephant. Berl. Tierarztl. Wschr. 27, 234-235.

Damman, Stedefeder, 1909. Tuberculosis diseases in elephants with human type mycobacterium. Deutsche Tierarztliche Wochenschrift 17, 345.

Evans, G.H., 1906. Hemorrahgic septicemia in elephants. J. Trop. Vet. Sci. 1, 263-268.

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.

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