Elephant
Bibliographic
Database

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Elephant Bibliographic Database
www.elephantcare.org

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

Chandrajith, R., Kudavidanage, E., Tobschall, H.J., Dissanayake, C.B., 2009. Geochemical and mineralogical characteristics of elephant geophagic soils in Udawalawe National Park, Sri Lanka. Environ. Geochem. Health 31, 391-400.
Abstract: Geophagy or deliberate ingestion of soils was observed among Asian elephants (Elephas maximus) in the Udawalwe National Park, Sri Lanka, for several years. The geochemical and mineralogical composition of the clayey soil layers which are purposefully selected and eaten by elephants in the park were studied, in order to identify the possible reasons for elephant geophagy. The concentrations of major and trace elements were determined by means of X-ray fluorescence spectrometry in 21 soil samples from eight geophagic sites and six soil samples collected from four non-geophagic sites. The mineralogical composition of selected soil samples was investigated using X-ray diffractometry (XRD). These geochemical analyses revealed that geophagic soils in the study areas are deeply weathered and that most of the elements are leached from the soil layers under extreme weathering conditions. The XRD data showed that the soils of the area consisted mainly quartz, feldspar, and the clay minerals kaolinite, Fe-rich illite, and smectite. Although no significant geochemical differences were identified between geophagic and non-geophagic soils, a clear difference was observed in their clay mineralogical content. Soils eaten by elephants are richer in kaolinite and illite than non-geophagic soils, which contain a higher amount of smectite. It is suggested that elephants in Udawalawe National Park ingest soils mainly not to supplement the mineral contents of their forage but to detoxify unpalatable compounds in their diet

Gandolf, A.R., Lifschitz, A., Stadler, C., Watson, B., Galvanek, L., Ballent, M., Lanusse, C., 2009. The pharmacokinetics of orally administered ivermectin in African elephants (Loxodonta africana): implications for parasite elimination
73. J. Zoo. Wildl. Med. 40, 107-112.
Abstract: Loxodonta africana are susceptible to a wide variety of parasites that are often treated with the broad spectrum antiparasitic ivermectin (IVM) based on empirical knowledge. The objectives of this study were to 1) measure plasma IVM levels following administration of 0.1 mg/kg IVM p.o., 2) compare plasma IVM levels following administration with regular versus restricted feed rations, 3) measure IVM excretion in feces, and 4) use these findings to generate dosing recommendations for this species. Using a crossover design, six African elephants were divided into two groups. Ivermectin was administered and typical grain rations were either provided or withheld for 2 hr. Blood and fecal samples were collected for 7 days following drug administration. After a 5-wk washout period, groups were switched and the procedure repeated. Plasma and fecal IVM were analyzed using high-performance liquid chromatography. There was no statistically significant difference detected in the pharmacokinetic data between the fed and fasted groups. Peak plasma concentration, area under the curve, and half-life for plasma ranged between 5.41-8.49 ng/ml, 17.1-20.3 ng x day/ml, and 3.12-4.47 day, respectively. High IVM concentrations were detected in feces. The peak concentration values in feces were between 264-311-fold higher than those obtained in plasma. The comparatively large area under the curve and short time to maximum concentration in feces indicate elimination prior to absorption of much of the drug. Plasma IVM concentrations were low when compared to other species. Based on these findings, administration of 0.2-0.4 mg/kg p.o. should be appropriate for eliminating many types of parasites in elephants, and could minimize development of parasite resistance

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

Hermes, R., Behr, B., Hildebrandt, T.B., Blottner, S., Sieg, B., Frenzel, A., Knieriem, A., Saragusty, J., Rath, D., 2009. Sperm sex-sorting in the Asian elephant (Elephas maximus). Anim Reprod. Sci. 112, 390-396.
Abstract: In captive Asian elephants, there is a strong need for production of female offspring to enhance reproduction, counter premature aging processes in female animals and reduce challenging management situations derived from husbandry of several bulls in one institution. Artificial insemination of flow cytometrically sex-sorted spermatozoa offers the possibility to predetermine the sex of offspring with high accuracy. The aims of this study were to determine a suitable semen extender and basic parameters for flow cytometrical sex-sorting of Asian elephant spermatozoa. In total 18 semen samples were collected by manual rectal stimulation from one bull. Sperm quality parameters and sex sortability of spermatozoa were evaluated after dilution in three semen extenders (MES-HEPES-skim milk, MES-HEPES, TRIS-citric acid) and DNA staining. MES-HEPES-skim milk was the only semen extender found suitable to sex Asian elephant spermatozoa. From 18 ejaculates collected, 12 were successfully sorted with a purity of 94.5+/-0.7% at an average sort rate of 1945.5+/-187.5 spermatozoa per second. Sperm integrity, progressive and total motility were 42.6+/-3.9%, 48.1+/-3.3%, 59.4+/-3.8% after DNA labelling, and 64.8+/-3.2%, 58.0+/-5.0%, 70.8+/-4.4% after sorting, respectively. After liquid storage of sorted spermatozoa for 12h at 4 degrees C, sperm integrity, progressive and total motility were 46.4+/-5.2%, 32.2+/-4.2% and 58.2+/-3.9%, respectively. The obtained results provide a promising base to inseminate Asian elephants with sexed semen

Thitaram, C., Pongsopawijit, P., Chansitthiwet, S., Brown, J.L., Nimtragul, K., Boonprasert, K., Homkong, P., Mahasawangkul, S., Rojanasthien, S., Colenbrander, B., van der Weijden, G.C., van Eerdenburg, F.J., 2009. Induction of the ovulatory LH surge in Asian elephants (Elephas maximus): a novel aid in captive breeding management of an endangered species
49. Reprod. Fertil. Dev. 21, 672-678.
Abstract: A unique feature of the reproductive physiology of Asian elephants (Elephas maximus) is the occurrence of two LH surges before ovulation, instead of one. An anovulatory LH (anLH) surge, the function of which is unknown, occurs consistently 3 weeks before the ovulatory LH (ovLH) surge that induces ovulation. Thus, the ability to induce an ovLH surge would be useful for scheduling natural mating or artificial insemination. The present study tested the efficacy of a gonadotrophin-releasing hormone agonist (GnRH-Ag) to induce LH surges during the follicular phase of the oestrous cycle, which resulted in varied LH responses, but generally none were as high as previously documented natural surges. Thus, for the ovulation-induction trials, nine females were administered 80 microg GnRH-Ag intravenously at three time periods during the oestrous cycle, namely the anovulatory follicular phase, the ovulatory follicular phase and the luteal phase. During the late anovulatory follicular phase, nine of 10 females (90%) responded with an immediate LH surge followed 15-22 days later by an ovLH surge or a post-ovulatory increase in progestagens. In contrast, despite responding to the GnRH-Ag with an immediate increase in LH, none of the females treated during other periods of the oestrous cycle exhibited subsequent ovLH surges. One cow got pregnant from natural mating following the induced ovLH surge. In conclusion, ovLH induction is possible using a GnRH-Ag, but only during a specific time of the anovulatory follicular phase

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

Bechert, U., Christensen, J.M., Nguyen, C., Neelkant, R., Bendas, E., 2008. Pharmacokinetics of orally administered phenylbutazone in African and Asian elephants (Loxodonta africana and Elephas maximus). J. Zoo. Wildl. Med. 39, 188-200.
Abstract: The pharmacokinetic parameters of phenylbutazone were determined in 18 elephants (Loxodonta africana and Elephas maximus) after single-dose oral administration of 2, 3, and 4 mg/kg phenylbutazone, as well as multiple-dose administrations with a 4-wk washout period between trials. After administration of 2 mg/kg phenylbutazone, mean serum concentrations peaked in approximately 7.5 hr at 4.3 +/- 2.02 microg/ml and 9.7 hr at 7.1 +/- 2.36 microg/ml for African and Asian elephants, respectively, while 3 mg/kg dosages resulted in peak serum concentrations of 7.2 +/- 4.06 microg/ml in 8.4 hr and 12.1 +/- 3.13 microg/ml in 14 hr. The harmonic mean half-life was long, ranging between 13 and 15 hr and 39 and 45 hr for African and Asian elephants, respectively. There was evidence of enterohepatic cycling of phenylbutazone in Asian elephants. Significant differences (P < 0.0001) in pharmacokinetic values occurred between African and Asian elephants for clearance (27.9 and 7.6 ml/hr/kg, respectively), terminal half-life (15.0 and 38.7 hr, respectively), and mean residence time (22.5 and 55.5 hr, respectively) using 2-mg/kg dosages as an example. This suggests that different treatment regimens for Asian and African elephants should be used. There were no apparent gender differences in these parameters for either elephant species

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.

Bechert, U., Christensen, J.M., 2007. Pharmacokinetics of orally administered ibuprofen in African and Asian elephants (Loxodonta africana and Elephas maximus). Zoo Wildl Med 38, 258-268.
Abstract: The pharmacokinetic parameters of S(+) and R(-) ibuprofen were determined in 20 elephants after oral administration of preliminary 4-, 5-, and 6-mg/kg doses of racemic ibuprofen. Following administration of 4 mg/kg ibuprofen, serum concentrations of ibuprofen peaked at 5 hr at 3.9 +/- 2.07 microg/ml R(-) and 10.65 +/- 5.64 microg/ml S(+) (mean +/- SD) in African elephants (Loxodonta africana) and at 3 hr at 5.14 +/- 1.39 microg/ml R(-) and 13.77 +/- 3.75 microg/ml S(+) in Asian elephants (Elephas maximus), respectively. Six-milligram/kilogram dosages resulted in peak serum concentrations of 5.91 +/- 2.17 microg/ml R(-) and 14.82 +/- 9.71 microg/ml S(+) in African elephants, and 5.72 +/- 1.60 microg/ml R(-) and 18.32 +/- 10.35 microg/ml S(+) in Asian elephants. Ibuprofen was eliminated with first-order kinetics characteristic of a single-compartment model with a half-life of 2.2-2.4 hr R(-) and 4.5-5.1 hr S(+) in African elephants and 2.4-2.9 hr R(-) and 5.9-7.7 hr S(+) in Asian elephants. Serum concentrations of R(-) ibuprofen were undetectable at 24 hr, whereas S(+) ibuprofen decreased to below 5 microg/ml 24 hr postadministration in all elephants. The volume of distribution was estimated to be between 322 and 356 ml/kg R(-) and 133 and 173 ml/kg S(+) in Asian elephants and 360-431 ml/kg R(-) and 179-207 ml/kg S(+) in African elephants. Steady-state serum concentrations of ibuprofen ranged from 2.2 to 10.5 microg/ml R(-) and 5.5 to 32.0 microg/ml S(+)
(mean: 5.17 +/- 0.7 R(-) and 13.95 +/- 0.9 S(+) microg/ml in African elephants and 5.0 +/- 1.09 microg/ml R(-) and 14.1 +/- 2.8 microg/ml S(+) in Asian elephants). Racemic ibuprofen administered at 6 mg/kg/12 hr for Asian elephants and at 7 mg/kg/12 hr for African elephants results in therapeutic serum concentrations of this antiinflammatory agent.

Harbarth, S., Samore, M.A., 2007. Antimicrobial resistance determinants and future control. Emerg Infect Dis 11, 794-801.

Ball, R.L., Brown, J. Preliminary results of a cabergoline trial in captive elephant with hyperprolactinemia.  2006 Proceedings American Association of Zoo Veterinarians.  174-176. 2006.
Ref Type: Conference Proceeding
Abstract: Introduction: An Asian elephant (Elephas maximus) at Busch Gardens Tampa Bay (BGT) was diagnosed with hyperprolactinemia, with a persistently elevated serum prolactin concentration greater than 15 ng/ml, by the Conservation & Research Center (CRC) laboratory in January 1996.  She also had a number of other problems, including uterine disorders that resulted in consistently elevated progesterone. In March 2002, she was given cabergoline orally at a dose of 1 mg twice weekly p.o. for 6 mo.  Cabergoline is a long-acting dopamine receptor agonist with a high affinity for D2 receptors.  It exerts a direct inhibitory effect on the secretion of prolactin.  Cabergoline (Dostinex®, Pfizer Inc. Kalamazoo, Michigan 49007 USA) was purchased from a local pharmacy.  Serum prolactin concentrations declined almost immediately after treatment initiation, followed about 1 mo later by a drop in progesterone to baseline.  Progesterone secretion remained low until November 2002 when she resumed cycling based on the observation of a normal luteal phase based on serum progesterone profile.  From November 2002 through January 2004 she exhibited four normal estrous cycles.  Prolactin secretion also remained within the normal range for elephants, over 1 yr after treatment withdrawal. This female suffered no adverse effects due to the cabergoline treatment.  There were no behavioral changes noted or changes in appetite. Given the need to increase reproductive rates of African elephants (Loxodonta africana) to prevent captive extinction, it might be efficacious to treat genetically valuable females with cabergoline in the hope it will reinitiate reproductive cyclicity. Nearly 1/3 of African elephants with hormone data are not cycling normally, and in an earlier study 1/3 of these (11 of 30) were found to have increased serum prolactin levels.
 
Methods and Materials:
A clinical trial was undertaken with six captive African elephant females that were identified as good candidates for a cabergoline treatment study (i.e., they are acylic and had mean prolactin concentrations of >15 ng/ml).  The treatment consisted of 1 mg cabergoline given twice weekly p.o. for 6 mo.  Serum was banked and then analyzed at the CRC for progesterone and prolactin. All elephants were thought to be otherwise healthy.  Because prolactin is known to be an inflammatory marker, all candidates were required to have a negative lateral flow immunochromatograpy (Rapid Test) and multiple antigen immunoassay (MAPIA) for Mycobacteria tuberculosis.

Results:
A summary of the results is given in Table 1.  The treatment period is complete for three elephants, all of which showed a decrease in prolactin levels.  Elephant 1 showed a good response while on treatment, but did not cycle and serum prolactin has subsequently risen to pretreatment levels.  Increasing the dose in Elephant 2 and 3 reduced prolactin to baseline levels, but again did not result in a return to ovarian cyclicity.  Elephant 4 was taken off the study after only a few doses due to increased aggressive behaviors.  This is believed to be due to changes in the group social dynamics and not related to the cabergoline, as this behavior has continued after withdrawal of the drug. Based on these findings, the two newest candidates, Elephant 5 and 6, with very high prolactin concentrations have been placed on 2 mg/twice weekly for 1 yr pending continuation of this project.

Discussion:
Normalization of prolactin levels facilitated the return of normal cycles in an Asian elephant, but none of the African elephants have resumed cycling so far.  Thus, while the use of cabergoline shows promise in reducing elevated prolactin levels in both Asian and African elephants, other factors may need to be considered or a longer course at higher doses may be required for treatment to be successful in reinitiating ovarian activity.  The latter suggestion is supported by two of the animals (Elephants 2 and 3) in this limited trial, in which a decline in prolactin occurred after the dose was increased.  Understanding the etiology of hyperprolactinemia in elephants may also help in returning females to normal cycling.Relapse of hyperprolactinemia is more common in humans with micro- or macroprolactinomas.  Chronic estrogen stimulation is also known to increase prolactin levels.  A proposed pathophysiology is that elevated estrogen levels from persistent cycling will lead to elevated prolactin levels and acyclicity.  A difference between the two species in the causes of and potential treatment options for hyperprolactinemia should also be evaluated more closely.

1Busch Gardens Tampa Bay, 3605 Bougainvillea Drive, Tampa, FL 33674 USA;2Smithsonian Institution, National Zoological Park, Conservation & Research Center, Front Royal, VA 22630 USA
ACKNOWLEDGMENTS
We would like to thank the participating zoos for their cooperation and patience during this trial.
LITERATURE CITED
1Brown, J.L., S.L. Walker and T. Moeller. 2004.  Comparative endocrinology of cycling and noncycling Asian (Elephas maximus) and African (Loxodonta africana) elephants.  Gen. Comp. Endocrinol. 136:360-370.
2 Colao, A., A. Di Sarno, P. Cappabianca, C. Di Somma, R. Pivonello, and G. Lombardi. 2003. Withdrawal of long-term cabergoline therapy for tumoral and non-tumoral hyperprolactinemia.  New Engl. J. Med. 349:20232033.
3 Ismail, M.S., G.I. Serour, U. Torsten, H. Weitzel, and H.P. Berlien. 1998. Elevated serum prolactin level with high-dose estrogen contraceptive pills. .Eur. J. Contracept. Reprod. Health Care. 3(1):45-50.
4 Montero, A.M., O.A. Bottasso, M.R.Luraghi, A.G. Giovannoni, and L. Sen. 2001. Association between high serum prolactin and concomitant infections in HIV-infected patients. Human Immunol.62: 191-196.
5 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. Annu. 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
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

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.

Ducummon, C.C., Berger, T., 2006. Localization of the Rho GTPases and some Rho effector proteins in the sperm of several mammalian species
440. Zygote. 14, 249-257.
Abstract: The acrosome reaction is a fundamental event in the biology of the sperm and is a prerequisite to fertilization of the egg. Members of the Rho family of GTPases and their effectors are present in the cytoplasm and/or plasma membrane overlying the acrosome of porcine sperm. We have implicated the Rho family of GTPases and the Rho-activated kinase, ROCK-1, in mediating the zona-pellucida-induced acrosome reaction. Others have implicated the Rho GTPase in regulating the ionophore-induced acrosome reaction in the sperm of several mammalian species as well as in motility of bovine sperm. In this study, the localization of the Rho GTPases (RhoA, RhoB, Rac1 and Cdc42) as well as the effectors RhoGDI, PI(4)P5K and ROCK-1, was determined in boar, human, rat, ram, bull and elephant sperm. The four GTPases were each present in the sperm head of all species examined. RhoGDI was expressed in the head and tail of sperm from all species except pig, where it was present only in the head. PI(4)P5K was expressed in both head and tail of sperm from all species, but expression was typically weaker in the tail. Finally, ROCK-1 was expressed in the heads and tails of all sperm except that of the boar, where it was present only in the acrosomal region. These observations taken together suggest that the expression of Rho GTPases in sperm has been conserved throughout mammalian evolution, most likely due to the role of these GTPases in regulating acrosomal exocytosis

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

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

Morris, S., Humphreys, D., Reynolds, D., 2006. Myth, marula, and elephant: an assessment of voluntary ethanol intoxication of the African elephant (Loxodonta africana) following feeding on the fruit of the marula tree (Sclerocarya birrea)
485. Physiol Biochem. Zool. 79, 363-369.
Abstract: Africa can stir wild and fanciful notions in the casual visitor; one of these is the tale of inebriated wild elephants. The suggestion that the African elephant (Loxodonta africana) becomes intoxicated from eating the fruit of the marula tree (Sclerocarya birrea) is an attractive, established, and persistent tale. This idea now permeates the African tourist industry, historical travelogues, the popular press, and even scholastic works. Accounts of ethanol inebriation in animals under natural conditions appear mired in folklore. Elephants are attracted to alcohol, but there is no clear evidence of inebriation in the field. Extrapolating from human physiology, a 3,000-kg elephant would require the ingestion of between 10 and 27 L of 7% ethanol in a short period to overtly affect behavior, which is unlikely in the wild. Interpolating from ecological circumstances and assuming rather unrealistically that marula fruit contain 3% ethanol, an elephant feeding normally might attain an ethanol dose of 0.3 g kg(-1), about half that required. Physiological issues to resolve include alcohol dehydrogenase activity and ethanol clearance rates in elephants, as well as values for marula fruit alcohol content. These models were highly biased in favor of inebriation but even so failed to show that elephants can ordinarily become drunk. Such tales, it seems, may result from "humanizing" elephant behavior

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.

Wiedner, E.B., Isaza, R., Galle, L.E., Barrie, K., Lindsay, W.A., 2006. Medical management of a corneal stromal abscess in a female Asian elephant (Elephas maximus). J. Zoo. Wildl. Med. 37, 397-400.
Abstract: A 47-yr-old female Asian elephant (Elephas maximus) developed a corneal stromal abscess in her right eye. The elephant was trained to open her eye for topical ophthalmic therapy, and was treated six times daily with antibiotics and an antifungal solution for almost 2 mo. Nonsteroidal anti-inflammatory drugs were used to control pain, and atropine was applied topically to dilate the pupil and provide additional comfort. Vascularization of the abscess began shortly after initiating therapy, and complete resolution was obtained by 7 wk

Wiedner, E.B., Isaza, R., Galle, L.E., Barrie, K., Lindsay, W.A., 2006. Medical management of a corneal stromal abscess in a female Asian elephant (Elephas maximus). Journal of Zoo and Wildlife Medicine 37, 397-400.
Abstract: A 47-yr-old female Asian elephant (Elephas maximus) developed a corneal stromal abscess in her right eye. The elephant was trained to open her eye for topical ophthalmic therapy, and was treated six times daily with antibiotics and an antifungal solution for almost 2 mo. Nonsteroidal anti-inflammatory drugs were used to control pain, and atropine was applied topically to dilate the pupil and provide additional comfort. Vascularization of the abscess began shortly after initiating therapy, and complete resolution was obtained by 7 wk.

Wynne, J., Greer, L. Management of digital osteomyelitis in an Asian elephant (Elephas maximus).
2006 Proceedings American Association of Zoo Veterinarians.  185-186. 2006.
Ref Type: Conference Proceeding
Abstract: A 47-yr-old female Asian elephant was diagnosed with osteomyelitis of the left front digit 5, involving phalynges 1 and 2. Based on culture results of Pseudomonas and Bacteroides, enrofloxacin and metronidazole rectal suppository treatment was started. Serum levels were measured and different formulations were developed to attempt to deliver appropriate drug levels. The osteomyelitis progressed over the next 55 days. Enrofloxacin was discontinued based on culture and sensitivities (C&S) and regional limb perfusion (RLP) using amikacin started. From this point on, daily treatments with RLP have been performed. The 3-g amikacin dose was based on 5% of the elephant's systemic dose.  Two weeks later, RLP with 6 g of ampicillin was started on alternate days based on C&S, and the following week, 400 mg fluconazole was added on a third day in response to C&S and tissue biopsies indicating invasive Candida. Despite aggressive medical therapy, radiographs and bone biopsy indicated the osteomyelitis continued. Surgery was performed 3 mo after systemic antibiotics were initiated.  All infected bone and tissue was identified with methylene blue, and removed.  Only the most proximal third of P1 remained post surgery.  Post surgery, daily sterile bandage changes were performed and rotational RLP treatment was continued with amikacin (8 g), ampicillin (15 g), and fluconazole (800 mg).  This daily treatment regime, with some drug adjustments, has been continued for 6 mo. One month after surgery P1 was radiolucent at the distal margin, and was progressing to a fragmented appearance, indicating the osteomyelitis may still be present.  Amikacin serum levels were collected post RLP, before the tourniquet was removed.  Systemic theraputic levels were reached, but not the recommended 10 times MIC. Amikacin was replaced with 12 g of ceftazidime in the RLP rotation. Two months post surgery a fragment of the remaining P1 was easily biopsied from the healing surgical tract with culture results indicating Enterococcus, but not Pseudomonas. Three months post surgery we reinstituted enrofloxacin suppositories at a higher dose. At 5 mo post surgery, cultures indicated that we had successfully eliminated Pseudomonas and anaerobic growth; however, the healing site continued to yield various gram-negative bacteria, including a Klebsiella resistant to ceftazidine.  We replaced ceftazidine with 12 g of ceftriaxone and continued ampicillin and fluconazole in the 3-day RLP rotation. Since this last medical alteration the remaining P1 fragments have been radiographically unchanged for 3 mo and the surgical wound has been reduced to a tract that is <2 mm in diameter and 4 cm deep. The current success of this treatment is attributed to a very tractable patient that has allowed daily medical care for over 8 mo. We are continuing her daily treatments and I will give an update on the progression of the case.

Zuba, J.R., Oosterhuis, J.E., Pessier, A.P. The toenail "abscess" in elephants: treatment options including cryotherapy and pathologic similarities with equine proliferative pododermatitis (canker).  2006 Proceedings American Association of Zoo Veterinarians.  187-190. 2006.
Ref Type: Conference Proceeding
Abstract: Foot problems potentially represent the single most important clinical disease of captive elephants.  Predisposing factors include obesity, lack of exercise, nail or sole overgrowth, improper foot care, poor hygiene, inappropriate enclosure surfaces, poor conformation, malnutrition and secondary skeletal disorders such as degenerative joint disease.  Furthermore, factors such as elephant management philosophy, disposition of elephants, facilities and competency of staff in caring for elephant feet will contribute significantly to the foot health of captive animals.  It is important to note that these conditions are rarely reported in free-ranging elephants. The elephant toenail abscess is characterized grossly by proliferative outgrowth of "crab meat-like" tissue that may acutely rupture through the surface of the nail wall and/or adjacent cuticle or sole. True abscess formation with localized collections of suppurative material is not a consistent clinical feature.  In most cases, the inciting cause of these lesions are typically not found and are likely due to one or more of the predisposing factors listed above.  Once established, these frustrating lesions require extensive, intensive and prolonged medical attention.  If not cared for properly, these wounds may progress to phalangeal osteomyelitis and the need for surgical intervention.  Sole abscesses are equally frustrating and difficult to manage with proposed etiologies similar to toenail lesions. There are no reports in the literature describing the pathology of the classic proliferative abscess tissue of the elephant nail abscess.  Although variously interpreted as fibrous or granulation tissue, the authors are unaware of previous histologic descriptions of this tissue.  Biopsy samples of toenail abscess tissue from two Asian elephants (Elephas maximus) at the San Diego Wild Animal Park (SDWAP) consisted of stratified squamous epithelium arranged in columns resembling horn tubules.  The predominant histologic finding was marked, near diffuse, hydropic degeneration of keratinocytes.  There were multifocal areas of suppurative inflammation with admixed bacterial colonies.  Inflammatory foci comprised only a small portion of the lesion and were interpreted as the external surfaces of the biopsy with likely secondary bacterial colonization. Because descriptions of the normal histology of the elephant toenail could not be located, a grossly normal toenail from a different Asian elephant was obtained to compare histologic features with those of the toenail abscesses.  Sections demonstrated formation of the toenail in a manner similar to that of the hoof of the horse and cattle with tubular, intertubular and laminar horn.  Primary and secondary epidermal laminae were identified.  Proliferative lesions of horn-producing epithelium associated with ballooning degeneration and inadequate keratinization of keratinocytes, have been described in horses as equine "canker" and coronary band dystrophy.  Equine canker is most commonly observed in the hind feet of draft horses and begins in the frog sometimes with extension to the sole and hoof wall.  Grossly, lesions are characterized by soft white papillary to "cauliflower-like" tissue associated with a foul odor. Similar to what is noted in elephant foot problems, predisposing factors for the development of equine canker include poor hygiene or wet environmental conditions. There is a lack of gross and histologic description of the normal nail and sole tissue of the elephant and further investigations are warranted.  A review of the anatomy and histology of the normal equine hoof may provide a basic understanding of the elephant nail until more specific and detailed elephant information is available.  From our investigation, the authors offer that a more accurate description of the elephant toenail abscess would be proliferative pododermatitis, the term synonymous with equine canker.  A more colloquial term such as "elephant canker" may be appropriate, as well. Canker in the horse is an uncommon but difficult to treat disease of the hoof.  Historically, treatment options for elephant toenail abscesses include corrective trimming, superficial debridement and application of topical disinfectants or antibiotics. Others have constructed innovative sandals to treat and protect the affected sole or nail with success. The use of regional intravenous perfusion of the affected limb with antibiotics has also been successful. Since the elephant nail abscess now appears to be histologically and clinically comparable to equine canker, this novel characterization of an old disease may offer unique insight for treatment.  In the least, it has provided our practice with a new list of treatment options and experienced equine clinicians for consultation who have been managing patients with a similar disease for many years. One of the Asian elephants at the SDWAP has had chronic toenail abscesses for over 2 yr. Radiographs of the affected digits, as reported by others to assess degree of involvement, have fortunately been negative for evidence of osteomyelitis.  Several bacterial and fungal cultures of deep tissue biopsies and swabs of affected lesions have resulted in a mixture of organisms with no consistent single etiologic agent.  Biopsies were found negative for presence of viral DNA (elephant papillomavirus and herpesvirus) by PCR.  Typical elephant foot care at the SDWAP includes trimming and debriding with hoof knives, foot soaks and topical antibiotics.  Although difficult, attempts are made in keeping the affected foot clean and dry.  Following recommendations for the treatment of equine canker, we recently implemented the routine use of cryotherapy in all elephants with proliferative pododermatitis with improved success in the control and recession of exuberant nail lesions. The proliferative tissue of the nail is first cleaned then disinfected, debrided, trimmed with hoof knives and allowed to dry. Modified brass branding tools with contact surfaces of variable size (2-5 cm diameter) and shape (round or ovoid) are placed into liquid nitrogen (-196 C) for several minutes and then placed directly on the cankerous tissue for 30-60 sec.  This process is then repeated 4-5 min later, following a complete thaw of tissue.  Within 24 hr, the cryoburned tissue becomes macerated and necrotic and is readily removed with gentle scrubbing.  Cryotherapy offers the advantage of destroying tissue to a deeper level than trimming alone and provides hemostasis, as well.  Because of decreased sensation at the cryotherapy treatment site, a memorable painful event is avoided and the elephant patient is more routinely accepting of this technique. With the use of hoof knives, we typically remove 2-3 mm of proliferative tissue before the patient refuses further treatment, presumably due to discomfort.  With cryotherapy, we are able to remove an additional 3-5 mm of tissue by cell freezing and necrosis.  The result is quicker resolution of cankerous lesions without the need for aggressive, and potentially painful, interventions. In conclusion, it appears that elephant nail abscesses can best be described as proliferative pododermatitis, or canker, as is seen in other species.  Further gross and microscopic descriptions of normal and pathologic nail or sole lesions are necessary.  Routine cryotherapy has shown promise in the treatment of these chronic, frustrating and potentially devastating lesions of our captive elephants.

Agnew, D.W., Hagey, L., Shoshani, J., 2005. The elephants of Zoba Gash Barka, Eritrea: part 4. Cholelithiasis in a wild African elephant (Loxodonta africana). J. Zoo. Wildl. Med. 36, 677-683.
Abstract: A 4.0-kg cholelith was found within the abdominal cavity of a dead wild African elephant (Loxodonta africana) in Eritrea. Analysis of this cholelith by histochemistry, electron microscopy, electrospray mass spectroscopy, and energy-dispersive x-ray spectroscopy revealed it was composed of bile alcohols but no calcium, bilirubin, or cholesterol. Bacteria were also found in the cholelith. Similar, but smaller, bile stones have been identified previously in other wild African elephants and an excavated mammoth (Mammuthus columbi). Choleliths have been reported only once in a captive Asian elephant (Elephas maximus). Elephants, along with hyraxes (Procavia capensis) and manatees (Trichechus manatus), are unique among mammals in producing only bile alcohols and no bile acids, which may predispose them to cholelithiasis, particularly in association with bacterial infection. Dietary factors may also play an important role in cholelith formation.

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.

Dumonceaux, G., Isaza, R., Koch, D.E., Hunter, R.P., 2005. Pharmacokinetics and i.m. bioavailability of ceftiofur in Asian elephants (Elephas maximus)
563. J. Vet. Pharmacol. Ther. 28, 441-446.
Abstract: Captive elephants are prone to infections of the feet, lungs, and skin. Often treatment regimens are established with no pharmacokinetic data on the agents being used for treatment in these species. A pharmacokinetic study using ceftiofur (1.1 mg/kg) was conducted in four adult female captive Asian elephants (Elephas maximus) at Busch Gardens in Tampa, Florida. Elephants were given both i.v. and i.m. administrations in a complete crossover design with a 3-week washout period between treatments. Blood samples were collected prior to drug administration and at 0.33, 0.67, 1, 1.5, 2, 4, 8, 12, 24, 48 and 72 h postadministration. Ceftiofur analysis was performed using a validated liquid chromatography/mass spectrophotometric (LC/MS) assay. Plasma concentrations for the i.m. samples were lower than expected. The mean C(max) following i.m. administration was 1.63 microg/mL with a corresponding T(max) of 0.55 h. Following i.v. administration, the median V(d(ss)) was 0.51 L/kg and a median Cl(p) of 0.069 L/kg/h. Mean i.m. bioavailability was 19%. The results indicate that ceftiofur used at 1.1 mg/kg i.m. could be useful in elephants when given two to three times a day or alternatively, 1.1 mg/kg i.v. once daily, depending upon the MIC of the pathogen

Duvivier, D.H., Votion, D., Vandenput, S., Lekeux, P., 2005. Aerosol therapy in equine species. The Veterinary Journal 154, 189-202.

Ingram, L.M., Isaza, R., Koch, D.E., Hunter, R.P. Pharmacokinetics of intravenous and intramuscular butorphanol in Asian elephants (Elephas maximus). 2005 Proceedings AAZV, AAWV, AZA Nutrition Advisory Group.  70-71. 2005.
Ref Type: Conference Proceeding
Abstract: Captive Asian elephants (Elephas maximus) are susceptible to lameness resulting from foot and joint pain.¹ In the past, opioid analgesics, such as the agonist-antagonist butorphanol, have been used clinically for pain management. However, dosages used in treating elephants were often extrapolated from data in horses, with the risk of administering either a sub-efficacious dose or an overdose, both of which are undesirable. In this study, six adult captive Asian elephants (five female, one male) were administered butorphanol intravenously (i.v.) and intramuscularly (i.m.) in a cross over design. The dose was 0.015 mg/kg for both routes with at least 21 days between administrations. Serial blood samples were collected immediately prior to butorphanol administration and at 5, 10, 20, 40 min, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, and 24 hr after injection.  The samples were collected into Li heparin vacutainer tubes and centrifuged to obtain plasma.  The plasma was separated into cryovials and frozen at -70°C until analyzed using a validated LC/MS assay with a LOQ of 0.025 ng/ml. The dosage selected for this pharmacologic study in elephants is within the recommended analgesic butorphanol dose range for horses.2  Following i.v. administration the median pharmacokinetic values that were calculated include: Vdarea, Vdss, Clp, MRT, and half life (t½). After i.m. injection the median Cmax, Tmax, and bioavailability (F) were calculated. The Vd data used for extrapolation from published literature on five domestic mammalian species correlated with the values found for elephants. Thus, Vd may be useful to extrapolate an efficacious dose in Asian elephants. Our preliminary results suggest a dosage of 0.015 mg/kg may provide analgesia without evidence of severe sedation. Further studies are necessary to determine the quality and duration of analgesia from the administration of butorphanol in elephants at this recommended dose.
LITERATURE CITED
1. Mikota, S.K., E. Sargent, and L. Georgeian. 1994. Medical Management of the Elephant. Endura Publishing House.
2. Plumb, D.C. 2005. Plumb's Veterinary Drug Handbook. Blackwell Publishing, Ames, Iowa. Pp. 102-105.

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.

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., 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., Riddle, H., Peloquin, C.A., 2005. Pharmacokinetics of ethambutol (EMB) in elephants
597. 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, 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

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

Neiffer, D.L., Miller, M.A., Weber, M., Stetter, M., Fontenot, D.K., Robbins, P.K., Pye, G.W., 2005. Standing sedation in African elephants (Loxodonta africana) using detomidine-butorphanol combinations. J. Zoo. Wildl. Med. 36, 250-256.
Abstract: Standing sedation was provided for 14 clinical procedures in three African elephants (Loxodonta africana) managed by combined protected and modified-protected contact and trained through operant conditioning. An initial hand-injection of detomidine hydrochloride and butorphanol tartrate at a ratio of 1:1 on a microg:microg basis was administered intramuscularly, with a dosage range of 50-70 mg (12.9-19.7 microg/kg) for each drug. The initial injection resulted in adequate sedation for initiation and completion of eight procedures, whereas supplemental doses were required for the remaining procedures. The dosage range for the supplemental injections of each drug was 4.0-7.3 microg/kg. Initial effect was noted within 3.0-25 min (mean = 11.6 min, SD +/- 5.9 min), with maximal effect occurring at 25-30 min for those procedures not requiring supplementation. In all but one procedure, this effect was maintained until the end of the procedure, which ranged from 47 to 98 min (mean = 74.7 min, SD +/- 18.8 min). No cardiac or respiratory depression was appreciated. Recovery after administration of reversal agents was rapid and complete, ranging from 2 to 20 min (mean = 9.0 min, SD +/- 7.0 min). On the basis of the authors' experience, recommended dosage ranges for reversal agents would be intravenous yohimbine (73.4-98.5 microg/kg), intravenous naltrexone (48.9-98.5 microg/kg), and intramuscular naltrexone (73.4-98.5 microg/kg). Approximately one-third to one-half of the total naltrexone dose should be administered intravenously. Mild adverse side effects limited to the gastrointestinal tract were observed in association with five procedures including abdominal distention with or without transient anorexia. Administration of reversal agents, encouraging exercise and water consumption, and administration of flunixin meglumine were helpful in the resolution of signs. In addition to gastrointestinal signs, slight ataxia was observed before initiation of surgical stimulation during one procedure in which 19.7 microg/kg of each drug was administered. On the basis of the procedures that did not require supplementation to initiate treatment and taking into consideration the potential for ataxia at higher doses, a starting dosage range of 14.7-16.2 microg/kg of both detomidine and butorphanol in a ratio of 1:1 on a microg:microg basis administered i.m. simultaneously is recommended

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

Plumb, D.C., 2005. Plumb's Veterinary Drug Handbook. Blackwell Pub Professional.

Suedmeyer, W.K., Oosterhuis, J., Kollias, G., Fagan, D., Hornoff, B., Dodam, J., Shafford, H. Elephant restraint device assisted anesthesia in an African elephant (Loxodonta africana). 2005 Proceedings AAZV, AAWV, AZA Nutrition Advisory Group.  189-191. 2005.
Ref Type: Conference Proceeding
Abstract: Modern elephant management programs often include the use of protected contact. This allows improved safety for the elephant staff but may limit access to medical conditions occurring in elephants.
A 27-yr-old female African elephant (Loxodonta africana) weighing an estimated 3,700 kg was anesthetized for evaluation of a chronic, progressive, fistulous tract of the left ventral mandible. The mandible was routinely cultured, flushed with diluted peroxide, chlorhexidine, betadine solution, or alternating antibiotics, based on microbial sensitivities. To properly assess the left mandible, the elephant had to be placed in right lateral recumbency, which was accomplished with the use of a commercially available rotational elephant restraint device (ERD). Because of the protected contact management program, right lateral recumbency could not be guaranteed at the time of immobilization. Malpositioning, tusk fracture and/or related injury could occur upon recumbency without the additional control afforded by the ERD. The ERD is a hydraulically operated unit that comfortably restrains an elephant, minimizing safety risks to the animal and staff. The ERD consists of one solid wall, three side panels, and hinged floor. The ends of the restraint are closed with moveable shift doors. The three side panels can be moved independently depending upon the size of the animal and are further subdivided with moveable "subpanels" to allow direct access to various areas of the animal. In addition, support straps help gently stabilize limbs when performing medical procedures. The unit is positioned within the elephant holding facility at the Kansas City Zoo. The unit was installed in 1994 during renovation of the elephant exhibit, whereupon the elephant management program was changed from free-contact to protected contact. The ERD is utilized for reproductive assessments, semen collection, transabdominal ultrasound, evaluation of integumentary wounds, ophthalmic and aural examination, and administration of injectable medications. However, no elephant had been anesthetized and rotated in the restraint. The affected animal could not be guaranteed to re-enter the ERD once rotated, but would enter and station in the ERD on a daily basis. Because of this, a conspecific was conditioned to allow rotation without the use of sedatives or tranquilizers, to prepare for the actual immobilization. Adjustments in strap placement, cushioning, critical evaluation of mechanical stability, and placement of hydraulic panels allowed staff to prepare for the actual immobilization, minimizing complications. The elephant was conditioned to enter and station in the ERD. After strapping the distal limbs, thorax and caudal abdomen for support, the elephant was immobilized with a combination of 3,000 IU of hyaluronidase (O'Brien Pharmacy, Kansas City, MO USA), 10 mg acepromazine maleate, and 7 mg etorphine hydrochloride (Wildlife Pharmaceuticals Inc., Fort Collins, CO USA) via pole syringe. Close monitoring of induction was performed and when stage III anesthetic plane was achieved, the elephant was rotated into right lateral recumbency, elevating the elephant 6 feet above the floor. No voluntary movement of the animal was noted while the restraint was in motion. Direct arterial blood pressure, indirect oscillometric blood pressure, blood gases, respiratory rate, excursion characteristics, cardiac rate and rhythm, and pulse oximetry was routinely monitored during the procedure. Anesthesia was maintained with intermittent boluses of etorphine hydrochloride. Intravenous physiologic fluids (lactated Ringers solution) were maintained via an i.v. aural catheter, and insufflation with oxygen was provided on a continual basis. Oral examination and palpation demonstrated an incomplete transverse fissure of the left mandibular molar, intact gingival, and proper dental occlusion with the upper arcade.  Digital radiographs of the left mandible were performed based on exposures obtained with a set of skeletonized jaws. Advantages of this diagnostic modality are the immediate imaging results, portability, and digital imaging and storage, and does not require a developer or fixative. Adjustments in radiographic angle and technique were made to obtain the best diagnostic image. Radiographic imaging demonstrated a sequestrum consisting of a fractured enamel plate  ²of the mandibular molar with a fistulous tract that coursed ventrally to communicate through the skin. The elephant was elevated 6 feet above the ground, which presented unique challenges. Because of the relatively small operating space, intubation was not possible, but insufflation was readily achieved and successful based on pulse oximetry trends. A commercial lift was utilized to elevate two large-animal circle anesthetic units to the level of the elephant's head. During immobilization the legs were cushioned and restraint straps removed to lessen the potential for occlusive damage to the tissues. The ERD allows an elephant to be positioned in either right or left lateral recumbency.
Upon completion of diagnostic procedures, the narcotic agent was reversed with 1,400 mg naltrexone hydrochloride (Zoopharm, Laramie, WY USA) administered 25% intravenously and 75% subcutaneously. The elephant awoke within 90 sec and was rotated to a standing position within the restraint. Thereafter, the elephant was confined in the restraint for approximately 45 min, until no untoward effects were likely to occur. The elephant was released from the restraint and resumed normal eating and drinking within 8 hr, and voluntarily entered the restraint within 2 wk following the procedure. The elephant was stable throughout the procedure; however, a predetermined objective for mean arterial blood pressures (<200 MAP) was not achieved. Hyaluronidase was utilized to promote rapid absorption of the narcotic and neuroleptic agents.³ Acetylpromazine was used to maintain peripheral perfusion by reducing the hypertensive effects of etorphine,¹ which has been documented in previous immobilizations of African elephants.^3-5 Etorphine hydrochloride, a powerful narcotic agent, has been successfully used as an immobilizing agent in both wild and captive African elephants.^3-5 Use of an ERD allowed full control of the immobilization, increasing safety for personnel, preventing injury to the elephant, and positioning the left mandible on the dorsal plane. Disadvantages are the elevated height of the elephant, relatively small operating space, and disrupted line of sight communication. A second procedure will be performed in the near future to address the fracture and subsequent sequestrum diagnosed during the first immobilization. The elephant is currently being conditioned to allow restraint in a holding stall that will allow greater access to the oral cavity and surgical manipulation of the affected mandible.
ACKNOWLEDGMENTS
We thank the staff of the Kansas City Zoological Park for their care, concern, and expertise in helping make this procedure a success.
LITERATURE CITED
1 Booth, N.H. Psychotropic agents. In: Booth, N.H., and R.E. McDonald (eds.). Veterinary Pharmacology and Therapeutics.  W.B. Saunders, Co., Philadelphia, PA. P. 329.
2 Fagan, V.D.A., J.E. Oosterhuis, and A. Roocraft. 2001. Captivity disorders in elephants: impacted molars and broken tusks. Der Zoologische Garten 71:281-303.
3 Honeymoon, V.L., G.R. Pettifer, and D.H. Dyson. 1992. Arterial blood pressure and blood gas values in normal standing and laterally recumbent African (Loxodonta africana) and Asian (Elephas maximus)    elephants. J. Zoo Wildl. Med. 23:205-210.
4. Kock, R.A., P. Morkel, and M.D. Kock. 1993. Current immobilization procedures used in elephants. In: Fowler,
M.E. (ed.).  Zoo and Wild Animal Medicine: Current Therapy 3. W.B. Saunders Co., Philadelphia, PA.  Pp. 436-441.
5 Raath, J.P. 1999. Relocation of African elephants. In: Fowler, M.E., and R.E. Miller (eds.). Zoo and Wild Animal Medicine: Current Therapy 4. W.B. Saunders, Co., Philadelphia, PA.  Pp. 525-533.

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

Abou-Madi, N., Kollias, G.V., Hackett, R.P., Ducharme, N.G., Gleed, R.D., Moakler, J.P., 2004. Umbilical herniorrhaphy in a juvenile Asian elephant (Elephas maximus)
696. J. Zoo. Wildl. Med. 35, 221-225.
Abstract: An umbilical hernia was diagnosed in a 2-wk-old Asian elephant (Elephas maximus) by physical and ultrasonographic examinations. Umbilical herniorrhaphy was elected because the defect was large (approximately 7 cm long and 10 cm deep) and could potentially lead to incarceration of an intestinal loop. General anesthesia was induced with a combination of ketamine, xylazine, and diazepam and maintained with isoflurane in oxygen. The hernial sac was explored and contained fibrous tissue, fat, and an intestinal loop but no adhesions. The hernial sac was resected and the body wall closed using the technique of simple apposition. Following a superficial wound infection, the surgical site healed with no further complications.

Dangolla, A., Silva, I., Kuruwita, V.Y., 2004. Neuroleptanalgesia in wild Asian elephants (Elephas maximus maximus)
662. Vet. Anaesth. Analg. 31, 276-279.
Abstract: OBJECTIVE: To evaluate the suitability of etorphine with acepromazine for producing prolonged neuroleptanalgesia in wild Asian elephants. ANIMALS: Ten adult wild elephants (four males, six females), free-roaming in the jungles of the north-western province of Sri Lanka. MATERIALS AND METHODS: Ten wild elephants were tranquilized for attachment of radio transmitter collars from September to November 1997, using Large-Animal Immobilon (C-Vet Veterinary Products, Leyland, UK), which is a combination of etorphine (2.45 mg mL(-1)) and acepromazine (10 mg mL(-1)). This was injected using projectile syringes fired from a Cap-Chur gun (Palmer Chemical Co. Inc., Atlanta, USA). A volume of 3.3 (2.5-4.5) mL Immobilon (6.12-11.02 mg of etorphine and 25-45 mg acepromazine) was injected intramuscularly after body mass estimation of individual elephants. RESULTS: The body condition of all darted elephants was good, and the mean (minimum-maximum) shoulder height was 225 (180-310) cm. The average approximate distance to elephants at firing was 26 (15-50) m. The average time to recumbency after injection was 18 (15-45) minutes. Nine out of 10 elephants remained in lateral recumbency (and did not require additional dosing) for a period of 42 (28-61) minutes. The respiratory and heart rates during anaesthesia were 7 (4-10) breaths and 52 (40-60) beats minute(-1), respectively. An equal volume (8.15-14.67 mg) of diprenorphine hydrochloride (Revivon, 3.26 mg mL(-1) diprenorphine; C-Veterinary Products, Leyland, UK) was given intravenously when the procedure was completed. Recovery (return to standing position) occurred in 6 (2-12) minutes after diprenorphine injection. Immediately afterwards, all elephants slowly retreated into the jungle without complications. Continuous radio tracking of the animals involved in this study indicated no post-operative mortality for several months after restraint. CONCLUSIONS/CLINICAL RELEVANCE: Etorphine-acepromazine combinations can be used safely in healthy wild Asian elephants for periods of restraint lasting up to 1 hour

de Oliveira, C.A., West, G.D., Houck, R., Leblanc, M., 2004. Control of musth in an Asian elephant bull (Elephas maximus) using leuprolide acetate
716. J. Zoo. Wildl. Med. 35, 70-76.
Abstract: The results of long-term administration of leuprolide acetate (LA) depot in a 52-yr-old Asian elephant bull (Elephas maximus) for control of musth are presented. Twelve injections were administered for 6 yr during our interpretation of early musth or "premusth." Intervals between musth periods during the study varied from 2 to 34 mo. Blood samples, drawn weekly, were assayed for serum testosterone concentrations; mean levels were 11.78 +/- 1.97 nmol/L throughout the first 26 mo of the study, 7.28 +/- 1.28 nmol/L during the following 21 mo, and 0.45 +/- 0.035 nmol/L in the last 34 mo of this study. Early musth signs ceased within 3 days of drug administration after 10 of 12 injections. The mean serum testosterone concentrations were significantly decreased by the last 34 mo of the study. The results suggest leuprolide is a suitable alternative for controlling or preventing (or both) musth in captive Asian elephants, although permanent reproductive effects may occur. Zoos and wildlife conservation institutions could benefit from the use of LA in Asian elephants to increase the male availability in captivity, consequently ensuring genetic diversity and the perpetuation of the species

Groendahl-Nielsen, C. Drunken Asian elephants (Elephas Maximus) from ryegrass hay. 2004 PROCEEDINGS AAZV, AAWV, WDA JOINT CONFERENCE.  368-369. 2004.
Ref Type: Conference Proceeding
Abstract: Copenhagen Zoo has maintained a herd of Asian elephants (Elephas maximus) since 1878. In 1999, the herd (2.3) was housed with separation of males and pairs of females. The elephants were fed concentrate, hay, vegetables, fruit, bread, sugar beets, and browse.On the day of presentation, keepers reported that the alpha female demonstrated pronounced body wide ataxia. Due to concerns of the dry moat, the elephant was moved into an indoor enclosure. On a visual examination, the elephant was found somewhat more cooperative than usual and severely ataxic. Rectal temperature was normal (36.9oC). Auscultation demonstrated normal peristaltic sounds. Oral mucosa was pink and moist. Keepers reported that the wrapped ryegrass hay had smelled oddly when the elephants were fed in the preceding days. However, the elephants had eagerly consumed it, even before their concentrate. The hay was inspected and clearly smelled of alcohol. A tentative diagnosis of ethanol intoxication -"drunken elephant" - was made.

Elephants reportedly have a taste for alcohol and will readily eat fermented hay. The local police department was contacted for assistance. After some persuasion, they agreed to bring a Breathalyzer (Lion Alcolmeter, model S-300, Sweden) to the zoo to assess the elephant.Approximately 15 kg of hay was put into a plastic bag for 30 min to allow accumulation of any vapors. This was conducted three times and in the third attempt, enough air was trapped to process and obtained a reading over 0.1% alcohol concentration. Direct analysis of exhaled air from the elephant was unsuccessful. A blood sample was collected from an ear vein and submitted for alcohol concentration analysis to a human forensic lab (Forensic Department, University of Copenhagen, Denmark). These tests provided a result of very low alcohol content (0.0024% - legal limit for humans in Denmark driving a vehicle is 0.05%). This amount of alcohol would not account for the ataxia.

The following day, the ataxia had not changed despite diet changes that returned the elephants to normal dry hay. After reviewing the literature and considering hay composition, the diagnosis was changed to ryegrass staggers.1,2 At this time, the elephant had a normal appetite but remained confined indoors due to ataxia. After 10 days, the keepers judged that although the elephant was somewhat ataxic, it was stable enough for outside access. However, it promptly staggered and fell into the moat. The elephant was dragged from the moat by an unaffected elephant, assisted by the keepers. After another 4 days, a noticeable improvement was present in the ataxia. After 16 days, the elephant was released safely outside.

Surprisingly, 4 days after the initial case presented, a second female elephant demonstrated signs of ataxia, then the 6-ton breeding bull became ataxic the following day. This was unexpected because the suspected hay had been promptly removed from all animals' diet. The bull was severely affected and made a slow recovery - 18 days before the ataxia resolved completely.If the mycotoxicosis had worsened, the elephants would have been treated with acepromazine or diazepam.2 In summary, the long onset of intoxication from ingestion of the fermented hay to the onset of clinical signs was surprising. The protracted recovery phase called for patience in both keepers and the veterinarian.

LITERATURE CITED
1. Mansmann, R. A., E. S. McAllister, and R. A. Pratt. 1982. Equine Medicine & Surgery. Am. Vet. Publ., Santa Barbara, California. Pp. 1212.
2. Mayhew, J. 1999. Clinical Neurology of the Horse. Seminar Notes, Pp. 24-25.

Sanchez, C.R., Murray, S., Montali, R.J., Spelman, L.H., 2004. Diagnosis and treatment of presumptive pyelonephritis in an Asian elephant (Elephas maximus). J Zoo Wildl Med 35, 397-399.
Abstract: A 37-yr-old female Asian elephant (Elephas maximus) presented with anorexia, restlessness, and dark-colored urine. Urinalyses showed hematuria, leukocyturia, isosthenuria, proteinuria, granular casts, and no calcium oxalate crystals. Bloodwork revealed azotemia. Urine culture revealed a pure growth of Streptococcus zooepidemicus resistant to sulfamethoxazole-trimethoprim but susceptible to cephalosporins. A presumptive diagnosis of pyelonephritis was made based on bloodwork, urinalysis, and urine culture. The animal was treated with intravenous ceftiofur, and intravenous and per rectum fluids were given for hydration. The elephant's attitude and appetite returned to normal, the abnormal blood parameters resolved, and urinary calcium oxalate crystals reappeared after treatment, supporting presumptive diagnosis. Follow-up ultrasonography revealed an abnormal outline of both kidneys with parenchymal hyperechogenicity and multiple uterine leiomyomas.

Saseendran, P.C., Rajendran, S., Subramanian, H., Sasikumar, M., Vivek, G., Anil, K.S., 2004. Incidence of helminthic infection among annually dewormed captive elephants. Zoos' Print Journal 19, 1422.
Abstract: This study was conducted to determine the prevalence of parasitic infections among captive elephants in Guruvayoor town in Kerala, India. Dung samples were collected from 44 and 55 elephants during 2000 and 2002, respectively, and examined for the presence of helminth ova. Of the 99 elephants, 17 (17.17%) were positive for helminths. The incidence of helminth infection decreased from 22.73% in 2000 to 12.73% in 2002. Among the positive dung samples, 10 (10.10%) had Strongylidae and 7 (7.07%) had Digenea. The low incidence of helminth infection among captive elephants in the studied area might be due to the regular annual deworming using albendazole (2.5 mg/kg body weight).

Singleton, C., Ramer, J., Proudfoot, J. Use of unpasteurized honey for treatment of a deeply infected wound in an African elephant   ( Loxodonta africana). 2004 PROCEEDINGS AAZV, AAWV, WDA JOINT CONFERENCE.  622-624. 2004.
Ref Type: Conference Proceeding
Abstract: Case Report
A 26-yr-old female African elephant (Loxodonta africana) received a deep laceration to the neck from the tusk of another elephant. The wound originated approximately 10 cm caudal to the middle of the right pinna, extended ventromedially, and penetrated multiple muscle layers. The wound was approximately 10-12 cm wide and 25-30 cm deep.

Initial treatment involved wound lavage with sterile saline twice daily, sulfadimethoxine/ormetoprim (Primor®, Pfizer Animal Health, Exton, Pennsylvania 19341, USA; 8.5 mg/kg p.o., b.i.d.), and ibuprofen (Pharmacia and Upjohn, Kalamazoo, Michigan 49001, USA; 2 mg/kg p.o., b.i.d. as needed). There was purulent discharge from the wound on day 5, therefore topical wound dressing was initiated. After wound lavage, the wound cavity was packed with laparotomy sponges coated with a 1:1 mixture of 1% silver sulfadiazine cream (BASF Corporation, Mount Olive, New Jersey 07828, USA) and an anti-inflammatory ointment (hemorrhoidal ointment, CVS Pharmacy Inc., Woonsocket, Rhode Island 02895, USA). Despite aggressive topical and systemic therapy, the wound became progressively more purulent, necrotic, and malodorous. On day 11, the wound dressing was changed from silversulfadiazine cream / hemorrhoidal ointment to laparotomy sponges coated with unpasteurized honey (Eisele's Raw Honey, Westfield, Indiana 46074, USA). On day 16, oral antibiotics were changed from sulfadimethoxine / ormetoprim to enrofloxacin (Baytril®, Bayer Corporation, Shawnee Mission, Kansas 66201, USA; 1.5 mg/kg p.o., s.i.d.) based on culture and sensitivity results. After 5 wk of therapy (day 51), enrofloxacin was discontinued due to poor patient compliance. Wound care from day 52 until completion of healing (12 additional weeks) consisted of twice daily wound lavage and dressing with unpasteurized honey. By day 101, wound care was decreased to once daily. On day 138 wound care was discontinued, and on day 143 the wound was considered healed.

Within 4 days of beginning topical treatment with honey, subjective scores of purulent exudate, necrotic tissue, and malodor began to improve. By day 29, the wound was no longer malodorous. Minimal necrotic tissue remained in the wound on day 37, and purulent discharge had resolved by day 90.

A single-dose oral enrofloxacin pharmacokinetic study was performed to evaluate serum and milk levels of the drug. Following oral administration of enrofloxacin at 1.5 mg/kg, serum levels were subtherapeutic at all time points over 24 hr.

Discussion
Unpasteurized, or raw, honey has been used as a medicine for centuries. Many ancient cultures used honey to treat skin wounds, gastric ulcers, diarrhea, eye disorders, and cough.7 There are many reports in the human medical literature of wound dressing with unpasteurized honey, but there are very few reports of its use in clinical veterinary medicine.4,5

The success of unpasteurized honey as a wound dressing is due to its antibacterial, antiinflammatory, immune-stimulating, tissue-debriding, and tissue-nourishing properties. High osmolality, phytochemicals, production of hydrogen peroxide, and stimulation of leukocyte activity contribute to the overall antibacterial activity of honey. Raw honey reduces inflammation by eliminating bacterial production of pro-inflammatory antigens and cytotoxins,8
reducing local edema by osmosis,6 and contributing antioxidants that scavenge free radicals.2 Immune system stimulation includes activation of neutrophils, stimulation of lymphocyte proliferation,1 and release of immune-mediator compounds by monocytes.11 Dressing wounds with raw honey often eliminates the need for surgical debridement.10 Honey improves tissue regeneration by stimulating the development of new capillary beds, thereby increasing nutrient delivery and oxygen supply to tissues.3,6 Raw honey also provides the moist environment necessary for proliferation of epithelial cells and fibroblasts.8

Honey is easy to use as a wound dressing. It can be spread directly onto wounds, soaked into gauze, or used to fill cavities. It generally causes no pain upon application.7 Plasma or lymph is drawn out of tissues by osmosis, creating a layer of dilute honey in contact with the wound surface; there is minimal adhesion of bandage materials to cause pain or tissue damage when dressings are changed.6 Honey dressings can be changed daily, but can be changed more frequently if the wound is infected or contaminated; bandages can be changed less frequently if the wound is clean and dry.6 Any residual honey is easily removed with warm water. Solidified honey can be returned to the liquid form by warming to 37°C. Honey should not be heated excessively because the enzyme that produces hydrogen peroxide is easily inactivated by heat.6 Although honey may contain clostridial spores, there are no published reports of wound botulism.

In this case, no adverse effects resulted from using unpasteurized honey as a wound dressing. Necrosis and malodor were greatly decreased within 16 days and purulent discharge was drastically reduced within 23 days of beginning treatment with honey. Subjectively, the wound healed faster and with less scar tissue than expected for this elephant as well as in comparison to wounds in other elephants. Raw honey likely provided the primary antibacterial activity during wound healing since enrofloxacin serum levels were subtherapeutic. Unpasteurized honey should be considered for topical treatment of deep, infected wounds in elephants.

ACKNOWLEDGMENTS
The authors thank Ellen Clark, RVT, Jennifer Niederlander, RVT, David Hagan, Barre Fields, Don Nevitt, Jill Sampson, Leslie Mackie, Adam Cheek, Niki Jordan, and Shea Earley for assistance with wound management, and Susan Mikota, DVM for consultation regarding the case.

LITERATURE CITED
1. Abuharfeil, N., R. Al-Oran, and M. Abo-Shehada. 1999. The effect of bee honey on the proliferative activity of human B- and T-lympocytes and the activity of phagocytes. Food Agric. Immunol. 11: 169-177.
2. Frankel, S., G.E. Robinson, and M.R. Berenbaum. 1998. Antioxidant capacity and correlated characteristics of 14 unifloral honeys. J. Apicultural Res. 37(1): 27-31.
3. Gupta, S.K., H. Singh, A.C. Varshney, and P. Prakash. 1992. Therapeutic efficacy of honey in infected wounds in buffaloes. Indian J. of Ani. Sci. 62(6): 521-523.
4. Harcourt-Brown, F.M. 2002. Honey to treat rabbit abscesses. Exotic DVM 3(6): 13-14.
5. Mathews, K.A. and A.G. Binnington. 2002. Wound management using honey. Compend. Contin. Educ. Pract. Vet. 24(1): 53-60.
6. Molan, P.C. 1998. A brief review of the use of honey as a clinical dressing. Primary Intention (Aust. J. Wound Manage.) 6(4): 148-158.
7. Molan, P.C. 1999. Why honey is effective as a medicine. 1. Its use in modern medicine. Bee World 80(2): 80-92.
8. Molan, P.C. 2001a. Why honey is effective as a medicine. 2. The scientific explanation of its effects. Bee World 82(1): 22-40.
9. Molan, P.C. 2001b. Honey as a topical antibacterial agent for treatment of infected wounds. World Wide Wounds. Http://www.worldwidewounds.com.
10. Subrahmanyam, M. 1993. Topical application of honey in treatment of burns. Br. J. Surg. 78(4): 497-498.
11. Tonks, A., R.A. Cooper, A.J. Price, P.C. Molan, and K.P. Jones. 2001. Stimulation of TNF-α release in monocytes by honey. Cytokine 14(4): 240-242.

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.

Dumonceaux, G., Hunter, R., Koch, D., Isaza, R. The absorption and distribution of ceftiofur in asian elephants (Elephas maximus). Proc Amer Assoc Zoo Vet.  80-81. 2003.
Ref Type: Conference Proceeding
Abstract: Captive elephants are prone to infections of the feet, lungs and skin as evidenced by clinical and necropsy reports.³  Antimicrobials are commonly used to treat these infections with or without culture and sensitivity information.  Often treatment regimens are established with no pharmacokinetic data on the agents being used in these species.  Many times antimicrobial dosage regimens are extrapolated from equine doses or are allometrically scaled from other domestic species dosage regimens.  There are only a few antimicrobials that have been studied for pharmacokinetic information in the elephant.  These include trimethoprim-sulfadiazine, oxytetracycline, amikacin, amoxicillin, penicillin,  and ampicillin.^1,2,5,7,8  When treating animals without the benefit of pharmacokinetic information, there is risk of either overdosing or underdosing the medication to the animal resulting in adverse effects or ineffective dosing and the possibility of developing antimicrobial resistant infections.  More treatment options are needed that are based on scientific information in order to treat these appropriately. A pharmacokinetic study using ceftiofur sodium (Naxcel, Pharmacia & Upjohn Company, Kalamazoo, Michigan  49001, USA) was performed in our captive Asian elephants (Elephas maximus) at Busch Gardens in Tampa, Florida.  Health status was determined by physical condition, complete blood counts, and serum chemistry parameters.

Elephants were randomly assigned to either an intravenous (IV) or an intramuscular (IM) administration group for the first administration.  At the end of this phase the animals were not used again for a minimum of three weeks to ensure that the ceftiofur had cleared their system.  Then the groups were switched so that the group receiving the IV injections on the first set of trials received the IM injections the second time around and vice versa.  The dosage of ceftiofur administered by either route was 1.1 mg/kg based on the recommended dosage ranges for cattle and horses.⁶ Blood samples were collected just prior to drug administration and at 0.33, 0.67, 1, 1.5, 2, 4, 8, 12, 24, 48, and 72 hours post-administration.  Samples were collected in lithium heparin tubes, centrifuged within 10 minutes after collection, the plasma separated into cryovials and these aliquots frozen at –80 C until assayed. Ceftiofur analysis was performed using a validated liquid chromatography/mass spectrophotometry assay.

Analysis showed a steady  decline in plasma levels for both IV and IM administrations through the first 12 hours.  The IV dosing samples showed further decline through 24 hours.  Levels at 48 and 72 hours were below detectible limits for this assay. The study overall shows a similar pattern in decline of plasma levels between IM and IV administration of ceftiofur sodium in these elephants.  Plasma concentrations for the IM samples were lower than expected.  This likely could be adjusted by administering ceftiofur at a higher dosage rate of 2.2 mg/kg.  This would result in an extremely large injection volume and necessitate increasing the number of injection sites.  Efficacy of this drug at this dose is also dependent on the MIC of the target organism. Results indicate that ceftiofur used at 1.1 mg/kg IM could be useful in elephants when given 2-3 times a day depending upon the type and location of infection.

ACKNOWLEDGMENTS
The authors express their appreciation to the elephant staff and veterinary department at Busch Gardens, Tampa for their assistance with animal handling and sample collection respectively.

LITERATURE CITED
1.  Bush, M., Raath, J.P., de Vos, V.,  Stoskopf, M.K. 1996. Serum oxytetracycline levels in free-ranging male African elephants (Loxoconta Africana) injected with a long-acting formulation.  Journal of Zoo and Wildlife Medicine, 27, 382-385.
2.  Lodwick, L.J., Duback, J.M., Phillips, L.G., Brown, C.S.,  Jandreski, M.A. 1994. Pharmacokinetics of amikacin in African elephants (Loxodonta Africana).  Journal of Zoo and Wildlife Medicine, 25, 367-375.
3.  Mikota, S.K., Sargent, E.,  Georgeian, L.  1994.  Medical Management of the Elephant, Indira Publishing House.  West Bloomfield, Michigan, U.S.A.
4.  Olsen, J.H. 1999.  Antibiotic therapy in elephants.  In Zoo & Wildlife Medicine:  Current Therapy 4. W.B. Saunders
5.  Page, C.D., Mautino, M., Derendorf, H.D.,  Anhalt, J.P. 1991.  Comparative pharmacokinetics of trimethoprim-sulfamethoxazole administered intravenously and orally to captive elephants.  Journal of Zoo and Wildlife Medicine,  22, 409-416.
6.  Plumb, D.C. 1994.  Veterinary Drug Handbook.  Iowa State University Press, Ames, Iowa
7.  Rosin, E., Schultz-Darken, N., Perry, B.,  Tears, J.A.  1993.  Pharmacokinetics of ampicillin administered orally in Asian elephants (Elaphus maximus).  Journal of Zoo and Wildlife Medicine, 24, 515-518.
8.  Schmidt, M.J. (1978) Penicillin G and amoxicillin in elephants: a study comparing dose regimens administered with serum levels achieved in healthy elephants.  Journal of Zoo Animal Medicine, 9, 127-136.

Hildebrandt, T.B., Strike, T., Flach, E., Sambrook, B.S., Dodds, J., Lindsay, N., Goeritz, F., Hermes, R., McGowan, M. Fetotomy in the elephant. Proc Amer Assoc Zoo Vet.  89-92. 2003.
Ref Type: Conference Proceeding
Abstract: There were several reports about dystocia and its treatment in elephants since they were kept in captivity in western zoos and safari parks. ^{1, 2, 3, 4, 5, 6, 7, 8, 9, 10}  Especially in the last two years there has been a dramatic accumulation of reports about birth associated problems (Tab. 1). Causes for this development are probably the intensified captive elephant breeding programs and the involvement of more older nulliparous cows.

Over the last 100 years, there were more dystocia cases in captive Asian elephants than in African elephants. ⁷  However, this difference seems to be abolished with enhanced number of pregnancies in African elephants by now. The fact of an increased percentage of dystocia cases in both species can have two consequences for captive management. Firstly, older nulliparous cows will be strictly excluded from breeding in the future or secondly, the birth management will be improved.

Three (Table 1, Em 4, 5; La 3) of 10 cows died from the consequences of dystocia in western zoological institutions over the last two years. Totally, there were eleven cases of fatal dystocia cases listed in the literature since 1972 (Table 2). ^{5, 6, 7}  The seven cesarian performed (Table 2) as the ultimate intervention to treat the dystocia in elephants ended all with euthanasia or death of the females. The following presentation will described a potential new way of birth management in the elephant, the fetotomy. The authors believe that the fetotomy is prospective tool instead of the unsuccessful cesarian for saving the life of the dam with severe dystocia.  This method is recommended by the authors as an ultimate tool besides all the other important preparations in pregnant cows for an upcoming birth. Most important classical preparations are following: (I) intensive physical exercise, (ii) optimization of the body weight with a pregnancy associated diet, (iii) training for safe handling in case of necessary intervention in free or protected contact.  The fetotomy was never applied before in elephants because of the limited exploration field and the high degree of skeleton calcification in comparison to domestic and exotic hoofstock. 

In this particular case it was firstly tried to remove the dead fetus by episiotomy. ^{2, 3, 4, 7, 9, 10} However, the episiotomy attempt failed due to he inability to extract a dead oversized or malpositioned fetus.  From the two options to leave the dead fetus inside the uterus despite the surgically opened genital tract or to cut out parts of the fetus it was decided to perform a fetotomy. The initial hesitation to perform such drastic and complicated procedure led to the complication of an emphysemic fetus and progressive peritonitis in the female even before the procedure started. Fetus was successfully removed in six parts using an extra long and durable carthorse embryotom (Thygesen's type). Unfortunately, the patient died 3 days later because of the treatment resistant peritonitis.

In conclusion, it was demonstrated that fetotomy can successfully be applied in elephants. The authors suggested in order to achieve a positive outcome for the dam to decide on such ultimate intervention earlier in the dystocia process. Active elephant birth management should always be prepared for dystocia treatment ranging from (I) the administration of oxytocin, (ii) rectal massage of the caudal birth channel, (iii) episiotomy to the last option (iv) of fetotomy to safe the life of the mother.  Based on the complex preparation for an elephant birth and the knowledge about the huge range of potential complications it is advised to consult veterinary elephant specialists well in advance to ensure maximum expertise and experience.

Acknowledgements
The authors like to thank Charlie Gray who helped us to collect the relevant data from the dystocia cases and the elephant staff from Whipsnade Wild Animal Park for their active support. We also like to acknowledge professor Peter Glatzel, DVM and Andrea Krause for helping with the logistic preparation.

Literature cited

1.Lang, E.M. 1963. Geburtshilfe bei einem Indischen Elefanten. Acta Trop. 20, 87-114.
2.Merkt, H., D., Ahlers, H., Bader, H.-P., Brandt, M., Boer and L. Dittrich. 1985a. Bildbericht über den Auszug eines toten Elefantenfetus (Elephas maximus) am 645. Tag p.c. und 65 Stunden nach Geburtsbeginn via Damschnitt (vorläufige Mitteilung). Praktischer Tierarzt 5: 377-378.
3.Merkt, H., D., Ahlers, H., Bader, H.-P., Brandt, M., Boer and L. Dittrich. 1985b. Der Damschnitt, eine geburtshilfliche Interventionsmöglichkeit bei einer Elefantenkuh. Deutsche tieraerztliche Wochenschrift 92: 428-432.
4.Merkt, H., D., Ahlers, H., Bader, D., Rath, H.-P., Brandt, M., Boer and L. Dittrich. 1986. Nachbehandlung und Heilungsverlauf bei einer Elefantenkuh nach Geburtshilfe durch Damschnitt. Berliner Münchner Tierärztliche Wschrift 99: 329-333.
5.Furley, C.W. 1993. A caesarean section in an elephant (The first in europe). Help-Newsletter,15: 2931.
6. Foerner, J.J. 1998. Dystokia in the Elephant. In: Fowler, M. E. & E., Miller (eds.): Zoo & Wild Animal Medicine. 4. Ed. W. B. Saunders Company, 522-525.
7.Lange, A., T.B., Hildebrandt, G., Strauss, O., Czupalla, F., Goeritz and W. Schaftenaar. 1999. Möglichkeiten und Grenzen der Geburtshilfe bei Elefanten. Verhandlungsbericht Erkrankungen der Zootiere 39: 47-58.
8.Fluegger, M., F. Goeritz, R. Hermes, E. Isenbuegel, A. Klarenbeek, W. Schaftenaar, K. Schaller and G. Strauss. 2001. Evaluation of physiological data and veterinary medical experience in 31 Asian elephant (Elephas maximus) births in six European zoos. Verhandlungsbericht Erkrankungen der Zootiere, 40: 123-134.
9.Schaftenaar, W. 1996. Vaginal Vestibulotomy in an Asian Elephant (Elephas maximus). 1996 Proceedings American Association Zoo Veterinarians,  434-439.
10. Schaftenaar, W., T.B., Hildebrandt, M., Fluegger, F., Goeritz, D.J., Schmidt, and G. West. 2001. Guidelines for veterinary assistance during the reproductive process in female elephants. Proceedings American Association Zoo Veterinarians, 348-355.

Note: See source for Table 1: Dystocia cases in captive elephants in the last 2 yr and Table 2: Known dystocia cases with a fatal oucome for the dam

Islam, S., 2003. Parasitic disease of elephant. In: Das, D. (Ed.), Healthcare, Breeding and Management of Asian Elephants. Project Elephant. Govt. of India, New Delhi, pp. 137-140.

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.

Ollivet-Courtois, F., Lecu, A., Yates, R.A., Spelman, L.H., 2003. Treatment of a sole abscess in an Asian elephant (Elephas maximus) using regional digital intravenous perfusion. Journal of Zoo and Wildlife Medicine 34, 292-295.
Abstract: Regional digital i.v. perfusion was used to treat a severe sole abscess associated with a wire foreign body in a 19-yr-old female Asian elephant (Elephas maximus) housed at the Paris Zoo. The cow presented with acute right forelimb lameness and swelling that persisted despite 4 days of anti-inflammatory therapy. Under anesthesia, a 10- x 0.5- x 0.5-cm wire was extracted from the sole of the right foot. There was a 2-cm-deep, 7-cm-diameter abscess pocket that was subsequently debrided. Regional digital i.v. perfusion was performed and repeated 15 days later, using cefoxitin and gentamicin on both occasions. Between treatments, the cow received trimethoprim-sulfamethoxazole and phenylbutazone orally. Within 2 days of administering anesthesia and the first perfusion treatment, the lameness improved dramatically. When phenylbutazone was discontinued 1 wk after the first treatment, the lameness had completely resolved. At the second treatment, there was no evidence of further soft tissue infection, and the abscess pocket had resolved.

Pathak, S.C., 2003. Restraint and chemical immobilization of elephants. In: Das, D. (Ed.), Healthcare, Breeding and Management of Asian Elephants. Project Elephant. Govt. of India, New Delhi, pp. 23-27.

Peloquin, C.A., 2003. Clinical pharmacology of the anti-tuberculoisis drugs. In: Davies, P.D.O. (Ed.), Clinical Tuberculosis. Arnold Publishers, London,England, pp. 171-190.

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.

Sarma, K.K., 2003. Managing troublesome bulls with special reference to musth in captive Asian elephants. In: Das, D. (Ed.), Healthcare, Breeding and Management of Asian Elephants. Project Elephant. Govt. of India, New Delhi, pp. 58-66.

Brumbaugh, G.W., 2002. Prophylactic use of antimicrobial drugs. In: Smith, B.P. (Ed.), Large Animal Internal Medicine. Mosby, St.Louis, pp. 1360-1363.

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.

Cheeran, J., 2002. Adverse drug experiences in elephants. Journal of Indian Veterinary Association Kerala 7, 61.

Cheeran, J.V., Chandrasekharan, K., Radhakrishnan, K., 2002. Tranquilization and translocation of elephants. Journal of Indian Veterinary Association Kerala 7, 42-46.

Emanuelson, K.A., Agnew, D.W. Wasting syndrome in a bull African elephant (Loxodonta africana). Proc Amer Assoc Zoo Vet.  142-145. 2002.
Ref Type: Conference Proceeding

Kreeger, T.J., Arnemo, J.M., Raath, J.P., 2002. Handbook of wildlife chemical immobilization. Wildlife Pharmaceuticals Inc., Fort Collins, Colorado, U.S.A.

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.

Sanchez, C.R., Murray, S.Z., Montali, R.J., Spelman, L.H. Medical Management of Acute Pylelonephritis in an Asian Elephant. Baer, C. K. American Association of Zoo Veterinarians Annual Conference.  162-164. 2002. 2002.
Ref Type: Conference Proceeding

Tongwongsa, S., Diskul, M.L.P., Kanchanapangka, S., Mahasawangkul, S., Lungka, G., Angkswanich, T., 2002. The use of an etorphine-acepromazine cocktail for immobilization and diprenorphine as it's antagonist in an elephant (Elephas maximus indicus). Thai Journal of Veterinary Medicine 32, 45-51.
Abstract: Etorphine hydrochloride (2.45 mg/ml) in combination with acepromazine maleate (10 mg/ml) is a very potent neuroleptanalgesic. The drug principally affects psychomotor activities. With a bundle of roughage still in his mouth, Plai Kum-Sand, a 3400 kgs, bull elephant, 35 years of age lay down 6 minutes after an intramuscularly injection. In lateral recumbency and snoring, the heart rate was 44 beats/minute with respiration at 4 breaths/minute. This heavy level of sedation was reversed quickly and successfully using 9.78 mg of the antidote, diprenorphine hydrochloride intravenously, 18 minutes after anaesthetic challenge. The bull opened his eyes 2 minutes afterward. He moved, stood upright, and started nibbling food 6 minutes 30 seconds after diprenorphine administration.

White, S.D., Evans, A.G., 2002. Hypersensitivity disorders. In: Smith, B.P. (Ed.), Large Animal Internal Medicine. Mosby, St.Louis, pp. 1202-1207.

 2001. The Elephant's Foot: Prevention and Care of Foot Conditions in Captive Asian and African Elephants. Iowa State University Press, Ames,Iowa, USA.

du Toit, J.G., 2001. Veterinary Care of African Elephants. Novartis and south African Veterinary Foundation, Pretoria, Republic of Southhttp://bigfive.jl.co.za./elephant_book.htm Africa.
Abstract: This manual is a project of the South African Veterinary Foundation and Novartis South Africa (Pty) Ltd. It is distributed by Wildlife Decision Support
PO BOX 74610, Lynnwood Ridge, Pretoria, RSA, 0040; Tel: +27 12991-3083; Fax: +27 12991-3851 Online:http://bigfive.jl.co.za./elephant_book.htm

Lekeux, P., Duvivier, D.H. Aerosol therapy. IVIS . 2001.
Ref Type: Electronic Citation

Mortenson, J., 2001. Determining dosages for antibiotic and anti-inflammatory agents. In: Csuti, B., Sargent, E.L., Bechert, U.S. (Eds.), The Elephant's Foot. Iowa State University Press, Ames, pp. 141-144.

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

Rietschel, W., Hildebrandt, T., Goritz, F., Ratanakorn, P. Sedation of Thai Working Elephants with Xylazine and Atipamezole as a Reversal. A Research Update on Elephants and Rhinos; Proceedings of the International Elephant and Rhino Research Symposium, Vienna, June 7-11, 2001.  121-123. 2001. Vienna, Austria, Schuling Verlag. 2001.
Ref Type: Conference Proceeding

Sarma, K.K., 2001. Musth in Asian Elephant. Central Zoo Authority, New Delhi, India.

Suresh, K., Choudhuri, P.C., Kumari, K.N., Hafeez, M., Hamza, P.A., 2001. Epidemiological and clinico-therapeutic studies of strongylosis in elephants. Zoos' Print Journal 16, 539-540.
Abstract: Elephants like other herbivores are susceptible to various diseases including internal parasitism. In Nehru Zoological Park (NZP), Hyderabad, India, clinical records of Asian Elephants for a period of 10 years (1987-96) were examined to determine the prevalence of strongylosis in relation to season, age and sex. Faecal samples from elephants of S.V. Dairy Farm (SVD), Tirupathi, were also screened from January to June for helminthosis. Faecal egg counts (EPG) were estimated by Stoll's dilution method. Analysis of old records revealed that in NZP strongylosis was predominant in summer (52.63%) and the prevalence was lower in animals below 15 years of age. Seven animals (63.64 and 87.5%) each tested positive for ova of strongyles in NZP and SVD, respectively. On treatment with albendazole (Kalbend, 5 mg/kg BW, PO), the animals completely recovered on the seventh day. Therapy resulted in decreases in the pretherapeutic mean EPGs of 700±128.89 (SVD) and 671.4±123.20 (NZP) to 78.57±30.53 and 50±21.79, respectively. The animals were monitored up to four weeks after therapy.

Bush, M., Stoskopf, M.K., Raath, J.P., Papich, M.G., 2000. Serum oxytetracycline concentrations in African elephant (Loxodonta africana) calves after long-acting formulation injection. Journal of Zoo and Wildlife Medicine 31, 41-46.
Abstract: Serum oxytetracycline pharmacokinetics were studied in 18 African elephant calves. Each elephant received separate injections of oxytetracycline at approximately 18 mg/kg i.m. and 8 mg/kg i.v. in a cross-over study. Blood samples were drawn at 0, 24, 48, 72 and 96 h postinjection. An additional sample was drawn 110 h before the animals were reinjected in the cross-over study and a final blood sample was drawn 48 h after the second dose. No lameness or stiffness was observed following i.m. injections. Serum oxytetracycline concentrations >0.5 µg/ml were present 48 h after initial dosing for all elephants (i.m., i.v., high or low dosage). Only elephants given the high i.m. dosage (18 mg/kg) maintained levels >0.5 µg/ml 72 h postinjection. No significant difference in serum oxytetracycline concentration with time was observed between the groups given different i.v. dosages. These studies demonstrated that quantifiable serum oxytetracycline concentrations can be maintained in young African elephants with a low-dosage multidose i.m. regimen.

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

Ramsay, E. Standing sedation and tranquilization in captive African elephants (Loxodonta africana). Proc. Am. Assoc. Zoo Vet.  111-114. 2000.
Ref Type: Conference Proceeding

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

Fowler, M.E., Miller, R.E., 1999. Zoo and Wild Animal Medicine Current Therapy 4. W.B. Saunders, Philadelphia.

Gage, L.J., Blasko, D.R., Galuppo, L.D. Diagnostics and treatment of severe swelling of the pharyngeal tissues of an African elephant (Loxodonta africana). Proceedings of the American Association of Zoo Veterinarians.  105-108. 1999. 10-9-1999.
Ref Type: Conference Proceeding

Kudo, S., Ishizaki, T., 1999. Pharmacokinetics of Haloperidol, An update. Clin. Pharmacokinet 37, 435-456.
Abstract: Haloperidol is commonly used in the therapy of patients with acute and chronic schizophrenia. The enzymes involved in the biotransformation of haloperidol include cytochrome P450 (CYP), carbonyl reductase and uridine diphosphoglucose glucuronosyltransferase. The greatest proportion of the intrinsic hepatic clearance of haloperidol is by glucuronidation, followed by the reduction of haloperidol to reduced haloperidol and by CYP-medicated oxidation. In studies of CYP-medicated disposition in vitro, CYP3A4 appears to be the major isoform responsible for the metabolism of haloperidol in humans. The intrinsic clearances of the back-oxidation of reduced haloperidol to the parent compound, oxidative N-dealkylation and pyridinium formation are of the same order of magnitude, suggesting that the same enzyme system is responsible for the 3 reactions. Large variation in the catalytic activity was observed in the CYP-medicated reactions, whereas there appeared to be only small variations in the glucuronidation and carbonyl reduction pathways. Haloperidol is a substrate of CYP3A4 and an inhibitor of CYP2D6. Pharmacokinectic interactions occur between haloperidol and various drugs given concomitantly, for example, carbamazepine, phenytoin, phenobarbital, fluoxetine, fluvoxamine, nefazodone, venlafaxine, buspirone, alprazolam, rifampicin (rifampin), quinidine and carteolol. Overall, drug interaction studies have suggested that CYP3A4 is involved in the biotransformation of haloperidol in humans. Interactions of haloperidol with most drugs lead to only small changes in plasma haloperidol concentrations, suggesting that the interactions have little clinical significance. On the other hand, the coadministration of carbamazepine, phenytoin, Phenobarbital, rifampicin or quinidine affects the pharmacokinectics of haloperidol to an extent that alterations in clinical consequences would be expected. In vivo pharmacogenetic studies have indicated that the metabolism and disposition of haloperidol may be regulated by genetically determined polymorphic CYP2D6 activity. However, these findings appear to contradict those from studies in vitro with human liver microsomes and from studies of drug interactions in vivo. Interethnic and pharmacogenetic differences in haloperidol metabolism may explain these observations.

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

Moore, R.M., 1999. Antimicrobial therapy in horses. In: Colahan, P.T., Merritt, A.M., Moore, J.N., Mayhew, I.G. (Eds.), Equine Medicine and Surgery. Mosby, St. Louis MO USA, pp. 163-175.

Moore, R.M., 1999. Antiinflammatory drug therapy in horses. In: Colahan, P.T., Merritt, A.M., Moore, J.N., Mayhew, I.G. (Eds.), Equine Medicine and Surgery. Mosby, St. Louis MO USA, pp. 155-163.

Olsen, J.H., 1999. Antibiotic therapy in elephants. In: Fowler, M.E., Miller R.E. (Eds.), Zoo and Wild Animal Medicine: Current Therapy 4. W.B. SaundersPhiladelphia, PA,USA, pp. 533-541.
Abstract: Like other species, elephants should be given appropriate antibiotic regimens to achieve success in therapy.  When selecting antibiotics, the clinician must evaluate the severity and location of the infection, the antibiotic sensitivities of the bacteria, the pharmacodynamics of the antibiotics, the potential toxicity of the drug, and the physical status of the animal.  Antibiotic therapy in elephants can present problems because of 1) inability to reasonably estimate body weight for proper dose calculation, 2) lack of appropriate dosage information, 3) difficulties with administration of the medication, 4) volume or cost of medication needed.

Papich, M.G. Antimicrobial therapy: Strategies for effective use of antimicrobials.  207-217. 1999.
Ref Type: Conference Proceeding
Abstract: Selecting the correct antibacterial drug is one of the most challenging therapies encountered in veterinary medicine. Optimum selection should be based on a logical, systematic approach. This paper will focus on some of the important strategies that can guide antibacterial drug selection in small animal patients.

Raath, J.P., 1999. Relocation of African elephants. In: Fowler, M.E., Miller, R.E. (Eds.), Zoo and Wild Animal Medicine: Current Therapy 4. W.B. Saunders, Philadelphia, PA, USA, pp. 525-533.

Sarma, K.K., 1999. Bizarre behaviour of an elephant during xylazine anaesthesia. Indian Veterinary Journal 76, 1018-1019.

Stegmann, G.F., 1999. Etorphine-halothane anaesthesia in two five-year-old African elephants (Loxodonta africana). Journal of the South African Veterinary Medical Association 70, 164-166.
Abstract: Anaesthesia of 2 five-year-old female African elephants (Loxodonta africana) was required for dental surgery. The animals were each premedicated with 120 mg of azaperone 60 min before transportation to the hospital. Before offloading, 1 mg etorphine was administered intramuscularly (i.m.) to each elephant to facilitate walking them to the equine induction/recovery room. For induction, 2 mg etorphine was administered i.m. to each animal. Induction was complete within 6 min. Surgical anaesthesia was induced with halothane-in-oxygen after intubation of the trunk. During surgery the mean heart rate was 61 and 45 beats/min respectively. Systolic blood pressures increased to 27.5 and 25.6 kPa respectively, and were treated with intravenous azaperone. Blood pressure decreased thereafter to a mean systolic pressure of 18.1 and 19.8 kPa, respectively. Rectal temperature was 35.6 and 33.9 degrees C at the onset of surgery, and decreased to 35.3 and 33.5 degrees C, respectively, at the end of anaesthesia. Etorphine anaesthesia was reversed with 5 mg diprenorphine at the completion of 90 min of surgery.

Abou-Madi, N., Kollias, G.V., Sturmer, A.T., Hackett, R.P. Umbilical herniorrhaphy in a juvenile Asian elephant (Elephas maximus). Proceedings AAZV and AAWV Joint Conference.  212-216. 1998.
Ref Type: Conference Proceeding

Ball, R.L. Carbon monoxide and carboxyhemoglobin in captive Asian (Elephas maximus) and African (Loxodonta africana) elephants. 1998 Proceedings AAZV and AAWV Joint Conference.  506-507. 1998. 1998.
Ref Type: Conference Proceeding

Elkan, P.W., Planton, H.P., Powell, J.A., Haigh, J.A., Karesh, W.B., 1998. Chemical immobilization of African elephant in lowland forest,southwestern Cameroon. Pachyderm 25, 32-37.

Honeyman, V.L., Cooper, R.M., Black, S.R. A protected contact approach to anesthesia and medical management of an Asian elephant (Elephas maximus).  Proceedings AAZV and AAWV Joint Conference.  338-341. 1998.
Ref Type: Conference Proceeding

Mortenson, J. Determining dosages for anti-inflammatory agents in elephants. Proceedings AAZV and AAWV Joint Conference.  477-479. 1998.
Ref Type: Conference Proceeding

Mortenson, J., Sierra S. Determining dosages for antibiotic and anti-inflammatory agents in elephants. Proceedings of the First North American Conference on Elephant Foot Care and Pathology.  50-55. 1998.
Ref Type: Conference Proceeding
Abstract: Clinical application of drug use in elephants for safe, reliable, and effective results necessitates the establishment of a treatment response curve or blood concentration profile for each drug and species (African vs Asian).  Because of the difficulty in obtaining accurate pharmacokinetic information, it is more common to select a drug dosage and frequency interval used in other species, specifically the cow and the horse.  Where treatment monitoring with serum concentrations of the drug are difficult to obtain, extrapolation of treatment regimens between species of extraordinary size difference may be done by metabolic scaling to establish drug dosage rates and frequency intervals.  The principle of metabolic scaling of pharmacokinetic parameters is based on the well established scaling of physiological processes across animals of various sizes.  The goals of this paper are to cover what antibiotics are currently used now with Asian and African elephants by surveying North American zoos, reviewing standard equine doses, discussing metabolic scaling attempts, and reviewing pharmacokinetic studies done. Based on the survey, zoo veterinarians generally are not utilizing metabolic scaling formulas to determine antibiotic and anti-inflammatory drug dosages for elephants.  It appears that several drugs are being dosed too frequently (amikacin, amoxicillin), and not frequent enough (trimethoprim-sulfamethoxazole) based on pharmacokinetic study results.  Metabolic scaling dosages and treatment intervals do not correspond well with antibiotic pharmacokinetic studies done in both African and Asian elephants.

Bosi, E.J., Kilbourn, A.M., Andau, M., Tambing, E. Translocation of wild Asian elephants (Elephas maximus) in Sabah, Malaysia. Proceedings American Association of Zoo Veterinarians.  302. 1997.
Ref Type: Conference Proceeding
Abstract: The East Malaysian State of Sabah is believed to be home to about 1000 wild Asian elephants (Elephas maximus).  Some forest habitat has been lost through agricultural development.  In some cases, elephants are stranded in small pockets of forest which are unable to sustain them.  The Wildlife Department of Sabah has adopted a policy of capturing and translocating these animals to wildlife forest reserves.  The capture of these wild animals is made possible using chemicals such as Immobilon (etorphine HCl and acepromazine maleate) and Xylazil-100 (xylazine HCl).  The reversal agents are Revivon (Diprenorphine) and Reverzine (Yohimbine), respectively.  A recent capture and translocation exercise carried out involving eight wild elephants employed xylazine hydrochloride.  The dose of xylazine used was calculated based on the diameter of the front footprint which provides information on body dimensions when actual weights are not available.  Xylazine doses used ranged from 100-550 mg with a mean of 0.209 mg/kg body weight.  Sedation was observed within 26 min after the darting.  The animals were then shackled and tethered.  The time for the capture operations ranged from 27-110 mins, with a mean of 72 min.  Xylazine is used again during the loading of the animals onto the lorries.  It is an effective sedative for wild elephants which can be adjusted or reversed.  The choice and used of this drug depends entire on the ability to track the animal after darting and the ability to maneuver the captive elephants into suitable locations for tethering prior to loading.  Heavy machinery is required to load the animals, unlike most other wild Asian elephant translocations were trained elephants are used to facilitate loading.

Hickey, J., Panicucci, R., Duan, Y., et, al., 1997. Control of the amount of free molecular iodine in iodine germicides. J. Pharm. Pharmacol. 49, 1195-1199.

Karesh, W.B., Smith, K.H., Smith, F., Atalia, M., Morkel, P., Torres, A., House, C., Braselton, W.E., Dierenfeld, E.S. Elephants, buffalo, kob, and rhinoceros:  immobilization, telemetry, and health evaluations.  Proceedings American Association of Zoo Veterinarians.  296-230. 1997.
Ref Type: Conference Proceeding

Osofsky, S.A., 1997. A practical anesthesia monitoring protocol for free-ranging adult African elephants (Loxodonta africana). Journal of Wildlife Diseases 33, 72-77.
Abstract: Twenty free-ranging adult African elephants in northern Botswana were immobilized with a mean (± SD) of 9.5 ± 0.5 mg etorphine hydrochloride and 2000 IU hyaluronidase by i.m. dart. The mean time to recumbency was 8.7 ± 2.4 min. All animals were maintained in lateral recumbency. The anaesthesia monitoring protocol included cardiothoracic auscultation; palpation of auricular pulse for quality and regularity; checking of rectal temperature, and monitoring of respiratory and heart rates. Results of basic physiological measurements were similar to those of previous field studies of African elephants immobilized with etorphine or etorphine-hyaluronidase. In addition, continuous real-time pulse rate and percent oxygen saturation of haemoglobin (SpO₂) readings were obtained on 16 elephants with a portable pulse oxygen meter. Duration of pulse oximetry monitoring ranged from 3 to 24 min (mean ±SD = 8.2 ± 4.8 min). Differences between minimum and maximum SpO₂ values for any given elephant ranged from 1 to 6 percentage points, evidence for relatively stable trends. The SpO₂ readings ranged from 70% to 96% among the 16 elephants, with a mean of 87.3 ± 2.8%. 15 of 16 elephants monitored with a pulse oximeter had mean SpO₂ values = 81 ± 2.4%, with 11 having mean SpO₂ values = 85 ± 1.5%. All 20 animals recovered uneventfully following reversal: diprenorphine at 23.3 ± 1.5 mg (IV) with 11.7 ± 0.5 mg IM, or 24 mg diprenorphine given all IV.

Pashov, D.A., Lashev, L.D., Matev, I.B., Kanelov, I.N., 1997. Interspecies comparisons of plasma half-life of trimethoprim in relation to body mass. Journal of Veterinary Pharmacology and Therapeutics 20, 48-53.
Abstract: The relationship between body mass and plasma half-life of trimethoprim was studied in 10 species of animals and man using published data. Log half-life was positively and significantly correlated to log body mass based on individual measurements in 23 herbivorous animals (P<0.01), in 29 herbivorous animals + pigs (P<0.01), in 27 ungulates (P<0.01), in 16 ruminants (P<0.01) and in 6 non-herbivorous mammals, except pigs (P<0.05). The correlation was described by the allometric equations: t0.5beta=27 W0.26 in herbivorous animals and t0.5beta=125 W0.32 in non-herbivorous animals except pigs.

Bush, M., Raath, J.P., de Vos, V., Stoskopf, M., 1996. Serum oxytetracycline levels in free-ranging male African elephants (Loxodonta africana) injected with a long-acting formulation. Journal of Zoo and Wildlife Medicine 27, 382-385.
Abstract: Thirteen adult free-living male African elephants (Loxodonta africana) were anesthetized and given 20-100 g of a long-acting tetracycline (OTC) preparation either i.m. or i.v.  Five dosages were established based on body measurements (the sum of the body length and the girth in centimeters)  Serum concentrations of OTC were measured 48 hr after injection.  Serum concentrations >/= 0.5 g/ml were measured in 11 of 12 elephants receiving OTC dosages of 52-133 mg/cm either i.v. or i.m.  The i.m. administration route produced serum concentrations from 0.75-1.6 g/ml in four of four elephants.  A dosage of 60-80 mg/cm i.m. or i.v. should provide a therapeutic serum concentration of OTC for at least 48 hr.  The use of an i.v. catheter avoids multiple i.m. injections of large drug volumes.

Coetsee, C., 1996. Elephant Translocations. Pachyderm 22, 81.
Abstract: Notes: Following immobilization for translocation of 670 elephants in family units in 1993, haloperidol (40 to 120 mg depending on body size) was used as a tranquilizer during transport. In addition, azaperone, (50-200 mg) was often administered to avoid aggression. Trilafon (perphenazine (100-300 mg) was administered to keep animals calm after their release into bomas.

Njumbi, S.T., Waithaka, J., Gachago, S., Sakwa, J., Mwathe, K., Mungai, P., Mulama, M., Mutinda, H., Omondi, P., Litoroh, M., 1996. Translocation of elephants: the Kenyan experience. Pachyderm 22, 61-65.

Schaftenaar, W. Vaginal vestibulotomy in an Asian elephant (Elephas maximus). Proceedings American Association of Zoo Veterinarians.  434-439. 1996.
Ref Type: Conference Proceeding
Abstract: Due to its dimensions, dystocia in elephants presents a difficult problem.  This paper describes the delivery of a dead calf by surgical intervention.  A vestibulotomy was performed under local anesthesia.  Complications in wound healing resulted in a permanent fistula of the vestibulum.  The difficulties in decision making and the interpretation of clinical signs are discussed.

Schmitt, D., Bradford, J., Hardy, D.A. Azaperone for standing sedation in Asian elephants (Elephas maximus).  Proceedings American Association of Zoo Veterinarians.  48-51. 1996.
Ref Type: Conference Proceeding
Abstract: Azaperone was used for standing sedation in four Asian elephants (Elephas maximus) in 93 trials at Dickerson Park Zoo (DPZ).  Procedures including surgical artificial insemination, semen collection, and routine foot trimming were completed while utilizing azaperone as a sedative.  All procedures were performed within an elephant restraint device.  Azaperone has proven to be a safe and reliable drug for facilitation of routine health and reproductive-related procedures in captive Asian elephants when administered at 0.30 mg/kg.  the procurement of azaperone in the United States has been difficult due to changing manufacturing and distribution procedures.  The utilization of an Investigational New Animal Drug permit from the Food and Drug Administration is described, to facilitate procurement of azaperone from Canada for use in the United States.

Singh, L.A.K., Nayak, B.N., Acharjya, S.K., 1996. Chemical capture of a problem-elephant in Bolangir, Orissa. Indian Forester, Special issue: wildlife management. 122, 955-960.
Abstract: A detailed account is given of the method used to capture an elephant which had been regularly (over 18 yr) entering villages in the Bolangir and Padampur areas of NW Orissa, and causing damage to buildings, eating stored grains and injuring humans. Some 45 people took part in the capture operation which involved the use of darts containing Immobilon (etorphine hydrochloride and acepromazine maleate) to the animal, and of (diprenorphine hydrochloride) for revival. The human antidote for (Nar can) was kept on hand. The communication system, the operational strategies used, and then care and revival processes adopted for the animal are described. It is thought that the animal (with a female) had originally been in the care of a mahout who was taken into custody for some crime so that the animals were abandoned. The female appeared to have been accepted back into the wild, while the male continued to follow the routes used by the mahout. The purpose of capture was to control or translocate the animal.

Still, J., Raath, J.P., Matzner, L., 1996. Respiratory and circulatory parameters of African elephants (Loxodonta africana) anaesthetised with etorphine and azaperone. J S Afr Vet Assoc 67, 123-127.
Abstract: Department of Companion Animal Medicine and Surgery, Medical University of Southern Africa, Medunsa, South Africa.
Respiratory rate, heart rate, blood-gas tensions (PO2 and PCO2) and pH of arterial (a) and peripheral venous (v) blood, concentration of haemoglobin in arterial blood (Hb), saturation of arterial haemoglobin with oxygen and the end-expiratory concentration of oxygen were measured in 22 juvenile African elephants (Loxodonta africana) anaesthetised with etorphine and azaperone during a period of 35-65 minutes after they had assumed lateral recumbency. Based on these parameters the alveolar-arterial and arterial-peripheral venous differences of PO2 [P(A-a)O2 and P(a-v)O2 respectively] and oxygen content of arterial blood (CaO2) were calculated. Elephants with body mass of < or = 600 kg showed statistically significant changes in the following parameters, compared with elephants with a body mass of more than 600 kg (x +/- SD): PaO2 (64 +/- 11 versus 82 +/- 8 mmHg), P(a-v)O2 (9 +/- 5 versus 22 +/- 9 mmHg), P(A-a)O2(37 +/- 16 versus 15 +/- 8 mmHg) and Hb (148 +/- 20 versus 130 +/- 10 g/l) (p < 0.05). These findings suggested a tendency towards impaired oxygen exchange in the lungs, reduced peripheral extraction of oxygen and elevated oxygen-carrying capacity of arterial blood in smaller elephants. These changes were theoretically attributed to the respiratory-depressant and sympathomimetic effects of higher dosages of etorphine used in the smaller elephants to maintain a clinically acceptable anaesthetic plane. Individual elephants spent 35-150 minutes under anaesthesia and all recovered uneventfully after reversal of etorphine with diprenorphine.

Thakuria, D.B., Barthakur, T., 1996. Management of musth in a male African elephant by chemical sedatives in the Assam state zoo, Guwahati. Indian Veterinary Journal 73, 339-340.

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.

Cheeran, J.V., Chandrasekharan, K., Radhakrishnan, K., 1995. Principles and Practice of Fixing Dose of Drugs for Elephants. 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. 430-438.
Abstract: The traditional thumb rule of determining dose in domestic animals has been Cat - 1/2, Dog - 1, Sheep and Goat - 3, Horse - 16, Cattle - 24. However this was valid only for galenicals like Tinctures and Pulvis and also to some extent for pure chemicals used as drugs like potassium iodide, ammonium chloride etc. Development of modern techniques like determination of half life and minimum effective concentration changed the course and pattern of determining the dose of drugs in animals as well as in man. Some drugs which are of low therapeutic margin is, even recommended considering the surface area of the body (e.g. antineoplastic drugs). Wild animals provide not enough number, for experimental purposes to arrive at a proper recommendation. In such circumstances pharmacologists often extrapolate the dose from their "evolutionary cousins" some of which are domestic animals. But unfortunately in elephants such "close cousins" do not exist neither in the wild nor in the domestic category. This makes fixing of dosage all the more difficult. Hence often the dose has been arbitrarily fixed from clinical experiences. The article details the above principles as well as lists of dose of various pharmacological and chemotherapeutic agents used in clinical practice in elephants (Table 1).

Ebedes, H. The use of long term neuroleptics in the confinement and transport of wild animals. Joint Conf AAZV/WDA/AAWV.  173-176. 1995. 1995.
Ref Type: Conference Proceeding

Fowler, M.E., 1995. Elephants. Restraint and handling of wild and domestic animals. Iowa State University Press, Ames, Iowa, USA, pp. 265-269.

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.

Osofsky, S.A. Pulse oximetry monitoring of free-ranging African elephants (Loxodonta africana) immobilized with an etorphine/hyaluronidase combination antagonized with diprenorphine. Joint Conference AAZV/WDA/AAWV.  237-277. 1995.
Ref Type: Conference Proceeding

Schumacher, J., Heard, D.J., Caligiuri, R., Norton, T., Jacobson, E.R., 1995. Comparative effects of etorphine and carfentanil on cardiopulmonary parameters in juvenile African elephants (Loxodonta africana).  Journal of Zoo and Wildlife Medicine 26, 503-507.
Abstract: Fourteen African elephants (Loxodonta africana) were immobilized with either etorphine hydrochloride (3.2 ± 0.5 µg/kg i.m.) or carfentanil citrate (2.4 µg/kg i.m.). Induction time with etorphine was significantly longer (30 ± 21 min) than with carfentanil (8 ± 2 min).  Immediately following immobilization all elephants were placed in lateral recumbency and respiratory rate, heart rate, and rectal body temperature were monitored every 5 min throughout the immobilization period.  Arterial blood samples, collected from an auricular artery, were taken 10 min after immobilization and every 15 min thereafter for up to 1 hr.  At the first sampling, mean values for arterial blood gas variables for etorphine immobilized elephants were pHa, 7.29 ± 0.03; PaCO₂, 53.4 ± 5.2 mmHg; PaO₂, 71.8 ± 13.8 mmHg; standard base excess (SBE), -1.6 ± 2.9 mEq/L; and HCO3, 25.7 ± 2.7 mEq/L. After 1 hr of immobilization, mean arterial blood gas values were pHa, 7.32 ± 0.06; PaCO₂ , 57.2 ± 9.6 mm Hg; and PaO₂ , 53.8 ± 10.5 mm Hg; SBE, 2.7 ± 1.4 mEq/L; and HCO_3-, 30.6 ± 1.6 mEq/L. For carfentanil immobilized elephants, blood gas values at the first time of collection were pHa, 7.28 ± 0.04; PaCO₂, 52.1 ± 2.8 mmHg; PaO₂, 78.3 ± 14.7 mmHg; SBE, -2.3 ± 24 mEq/L; and HCO_3-, 24.3 ± 2.1 mEq/L.  Sixty minutes after the first sampling, blood gas values of one elephant were pHa, 7.38; PaCO₂, 48.7 mmHg; PaO₂, 52 mmHg; SBE, 3.4 mEq/L, and HCO_3-, 28.8 mEq/L.  Over time there was a progressive decline in arterial PO2 in all elephants.  It is concluded that elephants immobilized with either etorphine HCl or carfentanil developed hypoxemia (PaO₂ < 60 mmHg) after 30 min of immobilization.  It is recommended that the administration of one of these opioid drugs be accompanied by supplemental oxygen, or followed by an inhalant anesthetic in 100% oxygen for prolonged procedures.  Diprenorphine or nalmefene reversal was rapid and uneventful in both the etorphine and carfentanil group.  No cases of renarcotization were noted. Additional excerpt: All elephants in the etorphine group (n=8) received diprenorphine at a mean dosage of 8.3 ± 1.1 µg/kg IV. Two elephants in the carfentanil group (n=6) were administered diprenorphine at a dosage of 8.9 µg/kg IV and IM.  Three elephants in this group received nalmefene hydrochloride.  One of the three elephants was given nalmefene 166.7 µg/kg both IV and SC. Two of the three elephants were given nalmefene IV and IM. The dosage was 88.9 µg/kg IV and IM in one elephant and 53.3 µg/kg IV and IM in the other. One elephant in the carfentanil group was administered nalmefene (88.9 µg/kg IV) followed by diprenorphine (8.9 µg/kg IM).

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

deSilva, D.D.N., Kuruwita, V.Y. Sedation of wild elephants (Elephas maximus Ceylonicus) using Detomidine HCL ("Domosedan") in Sri Lanka. Fifth International Congress of Veterinary Anesthesia.  1994.
Ref Type: Conference Proceeding
Abstract: Full text: Eight wild elephants weighing 3818-4500 kg were sedated using detomidine HCl 1% (Farmos) after being captured using Large Animal Immobilon (C-Vet) and revived with Revivon (C-Vet) in the process of wild elephant capture and translocation program carried out in Sri Lanka.  The total volume of detomidine used on each animal ranged from 2.0 to 2.5 ml using a Cap-Chur pistol.  Exsheathment of the penis in males was evident within 5 to 10 minutes of administration of detomidine.  From 5 minutes post-administration, gradual flaccidity of the trunk was observed and complete "limping" of the trunk was seen in 12 to 15 minutes.  Dribbling of urine, slaiva, ptosis, gradual cessation of ear flapping were the other changes indicating sedation.  Seven out of 8 animals remained standing and were nonresponsive to low threshold physical or auditory stimuli, but moved steadily when traction was applied on the ropes tying the legs.  With this dosage of the drug, animals could be loaded onto a truck within 30-45 minutes of medication and were ready for transportation.  Antisedan (Farmos) had to be given to one animal which adopted lateral recumbency after detomidine.  After sedating and loading into trucks, the elephants were transported to a distance of 40 to 100 km (average transport time was 8 hours) during which there was no need for further "topping-up".  Animals started eating and moving the trunk about 6 hours after detomidine administration but never adopted a recumbent position while being transported.  It is concluded that wild elephants are very sensitive to detomidine and the dosage needed is much lower (approximately 5.5 µg/kg) than that needed for some other species of animals (equine and bovine).

Dunlop, C.I., Hodgson, D.S., Cambre, R.C., Kenny, D.E., Martin, H.D., 1994. Cardiopulmonary effects of three prolonged periods of isoflurane anesthesia in an adult elephant. Journal of the American Veterinary Medical Association 205, 1439-1444.
Abstract: Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins 80523.
An adult 3500-kg female African elephant (Loxodonta africana) was anaesthetized 3 times for treatment of subcutaneous fistulas over the lateral aspect of each cubitus (anaesthesia 1 and 2) and for repair of a fractured tusk (anaesthesia 3). Lateral recumbency and anaesthesia were achieved with etorphine (anaesthesia 1 and 2) or etorphine and azaperone (anaesthesia 3). The trachea was intubated and anaesthesia was maintained by isoflurane and oxygen delivered through 2 standard large animal anaesthesia machines joined in parallel. The range of total recumbency time was 2.4 to 3.3 h. Breathing and heart rates, systemic arterial pressure, rectal temperature, PaO2, pH and end-tidal gases were monitored. After administration of etorphine, measurements were made while the elephant was recumbent and breathing air, then every 5 min (cardiovascular) or 15 min (blood gases) after the start of administration of isoflurane and oxygen. Tachycardia and hypertension were detected after administration of etorphine, but heart rate and systemic arterial pressure decreased to within normal ranges after administration of isoflurane and oxygen. The elephant remained well oxygenated while anaesthetized and breathing a high oxygen mixture. The elephant had an uneventful recovery from each anaesthesia.

Gross, M.E., Clifford, C.A., Hardy, D.A., 1994. Excitement in an elephant after intravenous administration of atropine. Journal of the American Veterinary Medical Association 205, 1437-1438.
Abstract: A 28-year-old Asian elephant (Elephas maximus) was anaesthetized for cesarean section to remove a dead calf. The elephant was sedated with azaperone, and atropine was administered i.v. 90 minutes later in preparation for induction of anaesthesia with etorphine HCl. Within a minute of the injection of atropine the elephant began swaying kicking and moving in an agitated manner around the stall. It was concluded that there is considerable variation among species in the toxicity of atropine, although development of toxicosis usually is associated with overdosage.

Hattingh, J., Knox, C.M., Raath, J.P., 1994. Arterial blood pressure of the African elephant (Loxodonta africana) under etorphine anaesthesia and after remobilisation with diprenorphine. Veterinary Record 135, 458-459.
Abstract: Six adult, male elephants (bodyweight approximately 5000 kg) were immobilized, with 8 mg etorphine (M99) for semen collection by electroejaculation. Before electrostimulation (about 10 minutes after the elephants initially became recumbent) their mean arterial pressure was 186 ± 25 mm Hg. During the electrostimulation procedure to which each elephant was subjected intermittently over a period of about 20 minutes using a rectal probe, the mean was 263 ± 30 mm Hg. After 10 to 15 minutes stabilization, 26 mg diprenorphine (M50/50) was administered i.v. The elephants adopted a rocking motion in an attempt to stand up. This motion was accompanied by wide fluctuations in arterial pressure which peaked at 245 ± 19 mm Hg immediately before they rose. Arterial pressure subsequently decreased to a mean of 200 ± 28 mgHg once they were standing. Since these values were higher than that previously observed in standing, conscious elephants (145 ± 3 mmHg) it appears the standing, remobilized elephants in this study were hypertensive. Possible reasons for this are discussed. It is suggested that in view of the observed and possible detrimental increase in arterial pressure during electrostimulation simultaneous blood pressure monitoring should be carried out when this procedure is employed.

Hattingh, J., Knox, C.M., 1994. Arterial blood pressure in anesthetized African elephants. South African Journal of Wildlife Research 24.
Abstract: A number of elephants previously captured in the Krueger National Park developed a pink frothy discharge from the external nares. Some of these elephants subsequently died and histopathological examinations indicated severe lung oedema.  In view of the current hypothesis that high blood pressure could be a causative factor, arterial blood pressure was measured in elephants immobilized with etorphine alone (n=71) and with etorphine/azaperone (n=109) and with carfentanil/azaperone (n=26) mixtures. Arterial pressure was found to be significantly lower in the groups immobilized with azaperone mixtures than in the group immobilized with etorphine alone (p < 0.05).  In addition, no cases of lung oedema were observed in animals immobilized with etorphine/azaperone and carfentanil/azaperone mixtures.  It is strongly recommended, therefore, that azaperone be added to immobilization mixtures when elephants are subjected to herding prior to darting. Additional excerpt: all elephants in this study were juveniles 200 to 1300 kg.  Group 1 (n=71) was immobilized with 4-8 mg etorphine; group 2 (n=109) was immobilized with 4-8 mg etorphine and 50-90 mg azaperone; and group 3 (n=26) was immobilized with 4-8 mg carfentanil and 50-90 mg azaperone.

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.

Lodwick, L.J., Dubach, J.M., Phillips, L.G., Brown, C.S., Jandreski, M.A., 1994. Pharmacokinetics of amikacin in African elephants (Loxodonta africana). Journal of Zoo and Wildlife Medicine 25, 367-375.
Abstract: Two adult females were given single i.v. injections of 8 mg/kg. Trials using 3 mg/kg and 6 mg/kg i.m. were conducted with three adult females. Serum concentrations of amikacin were measured serially over a 24-49 h period. After i.v. administration of 8 mg/kg, the elimination half-lives (t0.5) were 4.0 and 3.7 h, the volumes of distribution at steady state were 0.21 and 0.18 litres/kg, and total body clearances were 41.8 and 40.8 ml/h/kg. At i.m. doses of 3 and 6 mg/kg, the peak concentrations observed ranged from 4.8 to 8.4 µg/ml and 14.2 to 21.8 µg/ml, respectively. The time at observed peak concentration was between 1 and 3 h, and t0.5 ranged from 3.8 to 5.9 h for the lower dose and from 3.7 to 6.3 h for the higher dose. Following the single dose trials, one elephant was treated with amikacin at a dose of 7 mg/kg i.m. at 24 h intervals for 21 days, and serum amikacin concentrations were determined 2 to 4 times on each of 11 days. Mean (SD) peak serum concentration for this elephant was 19.0±2.8 µg/ml, and mean serum concentration at 24 h (through) was 1.7±0.4 µg/ml. There was indication in this one elephant of a mild, reversible renal tubular insult based on a slight transient elevation in serum creatinine and the presence of casts in the urine. These changes resolved soon after the end of treatment. These preliminary results suggest that amikacin administered at 6-8 mg/kg i.m. once every 24 h would be appropriate for elephants with bacterial infections suspected to be susceptible to amikacin.

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.

Spelman, L.H., Loomis, M.R., Davidson, G.S. Intravenous antibiotic therapy in hoofstock using a portable battery-powered infusion pump. Proceedings American Association of Zoo Veterinarians.  321-323. 1994.
Ref Type: Conference Proceeding
Abstract: Several factors limit successful antimicrobial therapy in exotic hoofstock. Relatively few antibacterial and antifungal drugs are available for oral or intramuscular administration in ruminants, and delivery is often challenging. Frequent problems with oral antibiotic therapy include poor palatability, variable absorption, flora changes, and rumen degradation  (e.g. trimethoprim). Intramuscular administration usually requires remote delivery. Drug volume and dosing interval must be adjusted to available dart sizes and the tolerance of the animal for frequent darting. In many species, the additional stress of the treatment regimen may be life-threatening. An outbreak of interdigital necrobacillosis, associated with Fusobacterium necrophorum, occurred in impala (Aepyceros melampus) and springbok (Antidorcas marsupialis) at the North Carolina Zoological Park in 1993. Several cases progressed to osteomyelitis involving one or more digits despite repeated debridement and intramuscular administration of either procaine-benzathine penicillin G (Ambi-pen TM, Butler Company, Columbus, Ohio, 43228, USA) or trimethoprim sulfadiazine (Di-trim R, Syntex Animal Health, West Des Moines, Iowa, 50265, USA). A method of intravenous antibiotic delivery was established using a portable, battery-powered infusion pump attached to the neck of the animal and programmed to deliver up to 5 days of continuous therapy.

Bechert, U., 1993. Anesthesia. Animal Keepers' Forum 20, 351-353.

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.

Goldenheim, P.D., 1993. An appraisal of povidone-iodine and wound healing. Postgrad. Med. J. 69, S97-S105.

Johnsingh, A.J.T., Joshua, J., Ravi, C., Ashraf, N.V.K., Krishnamurthy, V., Khati, D.V.S., Chellam, R., 1993. Etorphine and acepromazine combination for immobilising wild Indian elephants (Elephas maximus). Journal of the Bombay Natural History Society 90, 45-49.

Kock, R.A., Morkel, P., Kock, M.D., 1993. Current immobilization procedures used in elephants. In: Fowler, M.E. (Ed.), Zoo and Wild Animal Medicine Current Therapy 3. W.B. Saunders Company, Philadelphia, PA, USA, pp. 436-441.

Lloyd, M., Goddard, M., Zeinowicz, R., Harper, J.S., III, 1993. One approach to the removal of an aural rhabdomyoma in a 7 year old african elephant. Proceedings American Association of Zoo Veterinarians 115-119.

McKenzie, A.A., 1993. The Capture and care manual : capture, care, accommodation and transportation of wild African animals. Pretoria : Wildlife Decision Support Services : South African Veterinary  Foundation, Pretoria.

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.

Raath, J.P., 1993. Transportation of the African elephant (Loxodanta africana). 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. 493-498.

Raath, J.P., 1993. Chemical capture of the African elephant. 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. 484-511.

Rosin, E., Schultz-Darken, N., Perry, B., Teare, J.A., 1993. Pharmacokinetics of ampicillin administered orally in Asian elephants (Elephas maximus). Journal of Zoo and Wildlife Medicine 24, 515-518.
Abstract: The purpose of this study was to determine the pharmacokinetics of ampicillin in Asian elephants (Elephas maximus) and to relate this information to the in vitro activity of ampicillin against two pathogens isolated from one elephant.  A single oral dose of ampicillin trihydrate (8 mg/kg) was given to three elephants; body weights were estimated. Capsules containing the drug were hidden in oranges that were offered to the elephants, and ingestion was complete.  The ampicillin minimum inhibitory concentration (MIC) for a streptococcal and staphylococcal elephant isolate was 0.06 ug/ml. Mean peak serum ampicillin concentration (0.86 ug/ml) was reached 90 min after administration of the drug.  The mean area under the concentration-time curve (AUC) was 208.6 ± 106.4 ug x min/ml.  The mean terminal half-life was 53.7 ± 8.9 min. Ampicillin concentrations in serum remained above MIC for longer than 8 hr.

Still, J., 1993. Etorphine-azaperone anaesthesia in an African elephant (Loxodonta africana). Journal of Veterinary Anaesthesia 20, 54-55.

Swan, G.E., 1993. Drugs used for the immobilization, capture, and translocation of wildlife. The Capture and care manual : capture, care, accommodation and transportation of wild African animals. Pretoria : Wildlife Decision Support Services : South African Veterinary  Foundation, Pretoria.

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.

Appayya, M.K., Khadri, S.S.M.S., 1992. Chemical capture of wild elephants and their translocation carried out in Karnataka state. 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. 107-112.

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.

Chakraborty, T., Majumdar, B.K., 1992. Foot and mouth disease in captive Indian elephant. 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.

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.

Cheeran, J.V., Chandrasekharan, K., Radhakrishnan, K., 1992. Tranquilization and translocation of elephants. 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. 176.
Abstract: Full text:  A total of 140 captive rogue tuskers were successfully tranquilized and translocated during the period for April 1979 to December 1988.  Most of the animals were those used in festivals or in lumbering operations.  The requests handled by the tranquilization team were of urgent nature and no kunkies were available to assist the operation.  Hence the animals were tranquilized retaining certain amount of ambulatory property and not allowing the animals to assume recumbency.  After ascertaining complete sedation which took nearly 45 minutes after darting the limbs were noosed were polypropylene ropes and pulled by volunteers numbering from 15 to 20 on each rope on the forelimb.  The animals were also given oral and percussion commands and coaxed to move.  Animals could be moved on an average of 100 meters to be tied in a safe tethering area.  The chemical used at first was nicotine and was subsequently replaced by xylazine alone or its combinations for better margin of safety.  The combination of xylazine with acepromazine and ketamine was discarded due to photosensitization of elephants and subsequent skin lesions on the back of the elephants. The dose of xylazine varied from 100 to 120 mg/ton body weight.  The data show that 85% of the cases were attended while the bulls were in premusth or post-musth period indicating lack of sufficient precaution taken by the mahouts.

Cheeran, J.V., Chandrasekharan, K., Radhakrishnan, K., 1992. A case of ochlophobia in a tusker. 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. 176.
Abstract: Full text: An adult captive tusker to be used for ceremonial purpose could not tolerate crowd (ochlophobia - fear of the crowd). The animal was put on 2000 mg of chlorpromazine twice daily orally and behaved normally during the entire festival season of 6 months.  The animal again showed symptoms of fear of the crowd when the owner withdrew the drug.  So the animal was put on 100 mg haloperidol twice daily orally.  Thid relieved the symptoms very well but without sedation compared to chlorpromazine hydrochloride.

Cheeran, J.V., Chandrasekharan, K., Radhakrishnan, K., 1992. Transportation of elephants by rail. 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. 120-122.

Lahiri-Choudhury, D.K., 1992. Translocation of wild elephants. 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. 91-106.

Nayar, K.N.M., Radhakrishnan, K., Chandrasekharan, K., Cheeran, J.V., Ravindran, S., George, P.O., 1992. Anaesthesia for surgical manipulations in the elephant. 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. 156-158.
Abstract: Anaesthesia using chloral hydrate, thiopentone sodium, xylazine and ketamine was induced in ten elephants. The effects, duration of induction and anaesthesia were recorded. Post anaesthesia complications were not encountered in any of the animals. Surgical manipulations could be carried out under anaesthesia induced with these drugs.

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

Rao, K.T., Rama, Y., 1992. Capture of a wild elephant calf. 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. 118-119.

Ashraf, N.V.K., Johnsingh, A.J.T., Panwar, H.S., Sale, J.B., Joshua, J., Ravi, C., Krishnamurth, V. Chemical immobilization of wild Asian elephants: pharmacological, biological and ecological considerations. International Seminar on Veterinary Medicine in Wild and Captive Animals, Nov. 8-10, Bangalore, India.  21. 1991.
Ref Type: Conference Proceeding
Abstract: An analysis of pharmacological, biological and ecological parameters while immobilizing wild Asian elephants with Etorphine hydrochloride was done to establish their interrelationships and considerations during immobilizations. A significantly lower dose of Etorphine/1000 kg body weight (BW) has been used in India than in other Asian countries (P<091) There was no significant association between dosage and induction time (IT) in cases where immobilization was complete. While total dose of Etorphine used increased with increasing BW (r=0.618, P<0.0001), the dosage unit BW increased (r=0.705, P<0.001). Adding Acepromazine did not affect either the amount of Etorphine used or the IT. Sternal recumbency was reported in 4 out of 37 cases. Out of 26 cases, where search time (ST) and IT were differentiated, visual contact with the darted animal was lost on 13 occasions out of 46 dartings, mortality was 13% but none due to high dosage
Pharmacological considerations include choosing an appropriate dose, taking into account the biology of elephant and the drug's undesirable effects. Inability to access the health of the animal and predict its psot-darting reaction is an important consideration and constraint. As dosage and IT did not have any significant association with ST, the timely location of an immobilized animal depends on a combination of many ecological factors and operational difficulties. As most of these considerations are interrelated and difficult to put into practice, immobilization in the wild involves some amount of risk.

Blumer, E.S. A review of the use of selected neuroleptic drugs in the management of nondomestic hoofstock. Proc. Am. Assoc. Zoo Vet.  333-339. 1991.
Ref Type: Conference Proceeding

Lance, W.R., 1991. New pharmaceutical tools for the 1990's. Proceedings American Association of Zoo Veterinarians 354-359.

Mandlekar, B.D., Soni, J.L., Nema, S.K. Disintegrating trypanosomes in elephant; diagnosis and chemotherapy. International Seminar on Veterinary Medicine in Wild and Captive Animals, Nov. 8-10, Bangalore, India.  30. 1991.
Ref Type: Conference Proceeding
Abstract: Sudden change in behaviour of six elephants was observed violent in nature did not permit their use for tourist. They were losing their condition. Anorexia, pyrexia, and anemia vis-a-vis the infected elephants were lethargic,eyes shrunken with lacrimation and they became unresponsive to command. Disintegrating trypanosomes in elephants of Kanha National Park were diagnosed by blood sample. NSD findings were reported by other diagnostic laboratories. Chemotherapy with corridane (Hindustan antibiotic) was done. An elephant of average build was injected with 12.5 gms of corridane dissoved in 75 ml of dist. water subcutaneously. A single injection was effective for 3 months.  In recurrent the above dose need to be repeated. Berenil (Hoechst) @ 800 mg/ 100 kg body weight by deep IM route, revealed synergistic effects. Livferol 250 ml B.D. 15 days effectively managed anaemia and deranged liver function. Sugar cane was supplemented to check hypoglycaemia. Six elephants simultaneously affected were cured. Half dose of corridane has chemoprophelectic effect. Rehydration was done with 3 kg of Gur, common salt 510 gms, fresh water 60 liters for 4-5 days.

Marrs, T.C., 1991. Toxicology of oximes used in treatment of organophosphate poisoning. Adverse Drug Reactions and Toxicological Reviews 10, 61-72.

Page, C.D., Mautino, M., Derendorf, H.D., Anhalt, J.P., 1991. Comparative pharmacokinetics of trimethoprim-sulfamethoxazole administered intravenously and orally to captive elephants. Journal of Zoo and Wildlife Medicine 22, 409-416.
Abstract: Three healthy captive female African elephants (Loxodonta africana) were used to determine the pharmacokinetics of trimethoprim-sulfamethoxazole (TMP-SMZ) after a single i.v. and a single oral dose of 3.7mg/kg TMP and 18.3mg/kg SMZ.  A 2-mo wash-out period was allowed between the i.v. and oral trials.  An adult female Asian elephant (Elephas maximus) was also used in this investigation; however, pharmacokinetic parameters calculated from data from this animal were not used to calculate mean pharmacokinetic parameters for TMP-SMZ in African elephants.  Serum concentrations of TMP-SMZ were measured by high-performance liquid chromatography on blood samples collected via venous catheterization predose, over 12 hr after i.v. drug administration, and over 24 hr after oral drug administration.  For African elephants, the mean terminal half-life (t_1/2,z), clearance (CL), and volume distribution at steady state (Vd_ss) of TMP following i.v. administration were 1.4 + 0.7 hr, 856.0 + 114.0 ml/hr/kg, and 1.1 + 0.4 L/kg, respectively.  For SMZ, these parameters were 1.83 + 0.06 hr, 93.6 + 10.8 ml/hr/kg, and 0.2 + 0.02 L/kg, respectively. Following oral administration, the mean t_1/2,z was 3.0 + 1.1 hr, the maximum concentration (C_max) was 0.43 + 0.07 micrograms/ml at time (t_max) 1.7 + 0.6 hr, and the bioavailability (F) was 61.2 + 21.3% for TMP.  For SMZ, the mean t_1/2,z was 2.0 + 0.3 hr, the C_max was 30.7 + 2.5 micrograms/ml at t_max 3.0 + 1.0 hr, and F was 81.7 + 17.5%. Calculated pharmacokinetic parameters from this investigation were similar to values reported in horses.  Based on these findings, metabolic scaling should not be employed to calculate the dose of TMP-SMZ in elephants.

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

Kirkwood, J.K., Widdowson, M.A., 1990. Interspecies variation in the plasma halflife of oxytetracycline in relation to body weight. Research in Veterinary Science 48, 180-183.
Abstract: The relationship between halflife (t_1/2, minutes) of oxytetracycline and bodyweight (W, kg) between species of mammals and birds was examined using data collected from the literature. Linear regression of the logarithm of the halflife of the elimination phase of oxytetracycline following intravenous injection on the logarithm of bodyweight for a variety of species of mammals and birds revealed a significant correlation between species (r = 0.602, n = 13, P<0.05). The interspecies relationship was described by the allometric equation; t_1/2 = 160 W^0.20. This suggests that there is about a 14-fold variation in t^1/2 across the size range of terrestrial homeotherms, and provides a guide to dosage regime for species in which oxytetracycline kinetics have not been studied.

Hegel, G.V., Hanichen, T., Mahnel, H., Wiesner, H., 1989. Warts (papilloma/sarcoid) in elephant. Erkrankungen der Zootiere 31, 201-205.
Abstract: Warts ( Papilloma, Sarcoid) in  Elephants  ( Hegel,G.)1989; translated from German by Gerda Martin. Papilloma virus - from the group Papova virus - is considered  an etiological agents of wart- like skin changes in cattle, sheep, mountain goat, and rabbit. (ROSENBERGER,1970; ROLLE and MAYR, 1984). Equine sarcoid (PALMER. 1985) found in horses is most likely caused by bovine papilloma virus. The alternate name is based on clinical and morphological differences in the actual papilloma. In the initial stage, the sarcoid is similar to that of the papilloma; however in later stages, tumorous decay on the surface of the epidermis, and proliferation of the mesenchymal part of the tumor in the subcutis dominate (DIET and WIESNER, 1982). Wart- like changes in the skin of elephants as described by PILASKI et al (1987, 1988), proved to be caused by Herpes virus.  Such skin changes in elephants are not rare and require treatment since size and volume of the excrescences  may cause functional disturbances in the patient. Even if the animal's  general   well being  is not impaired, the importance of esthetics and hygiene should not be disregarded in a place where there are spectators and visitors (zoo, circus). The following paper reports findings of wart- like skin changes in elephants. Observations and Therapy In the elephants  kept in the Hellabrunn  Zoo, no case of papilloma or similar skin tumors had occurred since 1972. First case: In 5-28 - 1987, a ca. 18 month old female L.a. named " Sabi" arrived In Hellabrunn. This animal had a wart- like thickening of 1 cm at the dorsal end of the trunk. After 8 weeks, more of those such skin changes appeared on trunk and lower lip without  impairment in general well being. Treatment consisted of  one daily, subcutaneous injection of 1 amp. Chelidonium D7 (DHU Chelidonium majus L.), and application of fresh ??Schoellkraut  juice dabbed onto the warts but was unsuccessful.  After a change of treatment was made: 10 drops of Thuja D4 (DHU Thuja occidentalis L) and 20 drops Acidum nitricum D12 (DHU Acidum nitricum), orally, once a day, at separate times of the day, there remained, after 2 weeks, a wart on the lower lip the size of a cherry pit, and the before mentioned  wart on the dorsal end of  the trunk had now grown to the size of a cherry. Even the strength of Thuja LM 6 (DHU Thuja occidentalis L.)  20 drops, oral, the growth of the wart on the dorsal end of the trunk, now with a diameter of 5 cm, could not be stopped: Exstirpation had to be performed. Frequent  sucking had promoted strong ulceration.  A secondary infection  had set in,  the surface showed granular  tissue exuding blood and pus.

On 10 -  6 -  1987 the growth was exstirpated and tissue was sent for virolog. and histolog. examination. In addition, tissue was removed from a fresh small wart for vaccine. During the operation the animal was immobilized (anesthetic: 0.3 ml Immobilon* (large animal Immobilon Rc* - Vet. Ltd.),  10mg Xylacin, 150 IE Hyaluronidase i. m.). There were no complications during recovery. Two  weeks post op., the first vaccination was given, followed by a second vacc. four weeks there after, of 5.0 ml, subcut.., of an auto vaccine developed by the Institute for Medical Microbiology, Dept. of Infectious and Epidemic Medicine. In February 1988, there occurred another bout with wart- like growth on the ventral part of the trunk, lower jaw, shoulders and feet, some with a diameter of 15 mm.  From the sedated young animal tissue was taken from several newly grown warts for the manufacture of auto vaccine (sedation: "Hellabrunner Mischung" / 150 IE Hyaluronidase). After 10 days, the first vaccination was given, and by the time of the second vacc." Sabi" was free of externally visible skin changes.

On 6. 6. 1988, "Sabi" fell ill again. Over night she was covered with 48 warts,  with  diameters from 2mm - 15 mm on trunk and head, and 10 more on the chest.The attempt to "ice"  the warts with liquid nitrogen was not successful. Instead, coagulation of ca. 20 of the larger warts was used. The monopolar coagulation electrode of the Erbotom F 2 (Erbe Elektromedizin) coagulates reaching deeply  into the healthy zone of the surrounding tissue. As before, tissue for the manufacture of the auto vaccine was taken, as well as  0.5 ml of blood from the ear vein for the manufacture of a "own- blood"  nosode. (Large animal, premedication: 20 mg Xylazin i.m., 20 minutes later : 0.5 ml Immobilon R (large animal Immobilon R c - Vet Ltd.) and 150 IE Hyaluronidase i.m. The following day, "Sabi" was given the "own- blood" nosode at a strength of C5 (20 drops daily).In addition, she was vacc. once again. Since "Sabi" was free of warts at the time of the second vaccination -   given 4 weeks after the first - the "own- blood" treatment was discontinued. Shortly there after, however, several new warts cropped up (diameter ca. 1 cm), so that the "own- blood"  treatments were continued. Since that time "Sabi" has had no recurrences.Second case : The Indian elephant cow (E. maximus) , named "Dirndl" , age ca. 22 years, had been kept in the box next to "Sabi" since "Sabi's" arrival. They kept trunk contact. On 5-2-1988, "Dirndl" showed on the distal trunk a substantially increased raised area ca. 2 x 2 cm oozing blood. It seemed to be an injury from a metal rope used in off limiting. The wound was disinfected and treated twice a day with chloromycetin spray with Gentian violetR (Parke Davis).  After  one week  the growth had increased substantially  and on the surface,  it had a cauliflower-like ulcerated  appearance.Upon light touch or movement of the dorsal  trunk, blood appeard spontaneously.   Four days later, the growth was exstirpated, while the animal was standing. (Sedation: 2.2 ml Hellabrunn mixture / 150 Hyaluronidase i. m.) . The attempt to close the skin of the trunk over the wound failed because the tension in that area was too great.  The surface of the wound was cauterized and treated with ChloromycetinSpray with Gentian violet R (Parke Davis). Tissue for pathological and histological examination was sent out.  One week after the operation,  the area of the wound was  highly swollem and the wound was infected. Treatment: Several times a day, an  ablution with a 0.1 % Rivanol solutionnR (Asid - 2 Aethoxy-6.9-diamin  acridinlactat)  and application of Sulfonamid-Codliver oil salve (WDT = Sulfadimidin- Sodium- cod liver oil).  In addition, analogous to "Sabi" , once daily 20 drops of "own-blood" nosode,  potency C 5  given orally. Three weeks post. op., there could be clearly distinguished a limited relapse, an area of  6 x 9 cm rising  ca. 2 cm  above the healthy skin of the trunk. The surface looked like the first growth.  It was extirpated under general anesthetic  (Premed.:80 mg Xylazin i. m., 20 min. later: 1.8 ml ImmobilionR and 150 IE Hyaluronidase). In addition, the whole wound was coagulated  by monopolar coagulation electrode as above. Daily for 4 weeks, the wound  was brushed with a 1:5 wood tar -alcohol - solution.There were no complications during recovery. After 5 weeks , all that could be seen was a ca. 1.5 cm long small scar on the skin of the trunk.

Histomorphological Findings:  Fixation with formalin, embedding in paraffin; stain: Hemalaun-Eosin, connective tissue stain  in the manner of Masson. The histomorphological  findings based on the tissue samples of "Sabi" and "Dirndl"  are the  same, and agree  with the findings of 3 other skin tumor tissue taken from elephants of different origin (tab. 1). The tumors  consist mainly of fibroplastic cells  with more or less  abundant collagen fibers and blood vessels. The boundaries from the adjacent corium and lower skin is largely indistinct.  In all larger neoplasties , the covering epidermis has been preserved  at margins only due to superficial ulceration.  Here the P. acuta aseptica diffusa borders  are irregular and strongly profiled, the epithelium is acanthoid and hyperkeratotic. The nuclei of tumor cells  are considerably anisomorphic, some have gigantic nuclei. Mitosis is frequent. Due to the ulcerated epidermis , there is deep infiltration with infectious cells. Virological findings: From the extirpated tissue taken from the African Elephant "Sabi" ca. 3 g was homogenated, in addition, the cells were "opened" by defrosting and ultrasound, and the "cleared" tissue suspension was analyzed  for free virus particles after concentration and negative-contrasting with  electron microscopy .  At the same time, small tissue samples of 2 mm  from deeper epidermis layers  were fixed as usual for the ultrahistological exam , embedded in epoxy  resin, and ultra thin slices were scanned by the electron microscope. No papilloma virus was found  in the concentrated, cell free tissue extract or  the ultrathin slices of tissue samples .No virus particle of  any kind was found.

Discussion
To  show papilloma by culturing cannot be done since  no species of this genus can  be propagated  in cell cultures  with the exception of its original host. The failed  attempt to prove their presence with the electronmicroscope does not exclude a papilloma virus etiology in tumors. When virus particles are viewed in higher concentrations, the electron microscopic  proof is successful. Using ultrahistologyical methods the particles in cell nuclei can only be found when the few cells  of specific skin cells  are in the virus propagation stage. In the case of virally induced papilloma however, a true virus propagation is not necessary. In the last few years, it was found that equine sarcoid  can be caused  by bovine papilloma virus. But it was only the genome of the virus which could be isolated by means of gene technology (ALTMANN, 1980; HAUSEN, 1980); the virus itself could not.  The oncogenetic potency of the virus in heterologic hosts , without true virus production, has been established.  A broader spectrum of hosts  for , at least , the papilloma virus in cattle seems to be the case.  And a bovine papilloma induced skin fibromatose in  (a) horse has been reported (LANCASTER, 1979). This virus can also appear in wild 'cud chewers, perhaps even carnivores. It is in part also related to the human papilloma virus. The possibility of transfer to humans (LANCASTER 1982) as well as other mammals such as elephants  has not been proved but is probable. In comparing the histological findings of the 5 skin growths with those of the viral fibropapilloma in cattle and horse (called equine sarcoid here), the relative immaturity of the tumorous tissue is evident. It compares to the so- called sarcoid in horses. The sarcoid-like structure and the indistinct  separation from healthy tissue  speaks for a virus etiology and  morphologically a relapse can be expected. This occurred in both of the clinically described cases.

A differential diagnosis excludes a Herpes virus infection, as described by PILASKI et al. (1987, 1988) in elephants on the basis of different histological findings. Inclusions could not be found in any of the cases. The warts on the elephants were clinically similar to the well known sarcoids in horses (DIETZ and WIESNER, 1982). The two sick animals were in "trunk contact" occupying adjacent boxes. Almost one year after the arrival of  "Sabi" who had warts, "Dirndl" fell sick. That points to the infectious nature of warts. The relapse after the first operation on "Dirndl" suggests that the extirpation of the growths was not complete. This may be related to the fact that the animal was standing  and only sedated. In contrast , the extirpation of the "relapse" was carried out on a fully immobilized animal and with the use of the Erbotom F 2  for coagulation including the adjacent tissue.  We know of various 'wart therapies' in human medicine with differing success. The various treatments employed in the one and one half years of "Sabi's" illness can be labled neither successful, nor unsuccessful. The use of auto vaccine which is analogous  to a "stable specific " vaccine in the treatment of papilloma in cattle, could  perhaps have triggered the recurrence of warts at the  conclusion of the vaccination treatments. That would favor the etiology of a virus 'picture.' The influence of the 'burn' or extirpation of a single or more growths which returned, in the surrounding growths cannot be determined. It remains inconclusive if the use of the "own- blood" nosode C 5 aided the successful therapy , since the necessity  to fight a recurrence had not yet occurred.

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

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.

Welsch, B., Jacobson, E.R., Kollias, G.V., Kramer, L., Gardner, H., Page, C.D., 1989. Tusk extraction in the African elephant (Loxodonta africana). Journal of Zoo and Wildlife Medicine 20, 446-453.
Abstract: Unilateral dentoalveolar abscesses and/or tusk fractures were identified and tusk extractions performed in seven 3.5-21-yr-old African elephants (Loxodonta africana) of both sexes weighing 650-3,000 kg.  Following immobilization with etorphine hydrochloride or carfentanil citrate, six of seven elephants were intubated and maintained on a 1-1.5% halothane in oxygen mixture; one elephant was maintained in lateral recumbency by multiple i.v. injections of etorphine.  All elephants were positioned with the affected tusk up.  For one elephant, two surgical procedures were required to remove the tusk.  In six of seven elephants, the tusks were sectioned transversely and the tusk wall thinned by enlarging the pulp cavity with carbide burs.  In those tusks with remaining pulp, the pulp was removed with stainless steel rods and hooks.  Next, the tusk was sectioned longitudinally into three or four segments using a wood saw within the pulp chamber.  bone gouges, osteotomes, and a mallet were used to free the outer epithelial and alveolar attachments from the tusk.  Starting with the smallest segment, the sections were removed using long screwdriver-shaped stainless steel rods.  The alveolar chamber was then periodically flushed postsurgically with a dilute organic iodine solution.  For six of seven elephants, complete granulation of the alveolar chamber was evident by 4 mo postsurgery; the seventh elephant showed partial healing with granulation tissue at 2 mo following surgery.

Briggs, M., Schmidt, M., Black, D., Roach, R., Opdahl, J., Stark, G., Owens, D., Driver, M., 1988. Extraction of an infected tusk in an adult African elephant. Journal of the American Veterinary Medical Association 192, 1455-1456.
Abstract: An 18-year-old African elephant was determined to have a nonrepairable crack in its left tusk. Treatment included extraction of the tusk, using rotational and extractional forces, and administration of antibiotics, followed by 1 year of flushing the opened tusk cavity with warm tap water. Two years after surgery, the elephant was healthy, and the tusk cavity was 80% filled with normal tissue.

Dunlop, C.I., Hodgson, D.S., Cambre, R.C., Kenney, D. Prolonged isoflurane anesthesia of an adult elephant on two occasions. Veterinary Surgery 17[3], 167-168. 1988.
Ref Type: Abstract

Heard, D.J., Kollias, G.V., Webb, A.I., Jacobson, E.R., Brock, K.A., 1988. Use of halothane to maintain anesthesia induced with etorphine in juvenile African elephants. Journal of the American Veterinary Medical Association 193, 254-256.
Abstract: Excerpts: Sixteen 3- to 5-year-old African elephants were anesthetized one or more times for a total of 27 diagnostic and surgical procedures.  Xylazine (0.1 ± 0.04 mg/kg of body weight, mean ± SD) and ketamine (0.6 ± 0.13 mg/kg) administered IM induced good chemical restraint in standing juvenile elephants during a 45-minute transport period before administration of general anesthesia.  After IM or IV administration of etorphine (1.9 ± 0.56 micrograms/kg), the mean time to lateral recumbency was 20 ± 6.6 and 3 ± 0.0 minutes, respectively.  The mean heart rate, systolic blood pressure, and respiration rate during all procedures was 50 ± 12 beats/min, 106 ± 19 mm of Hg, and 10 ± 3 breaths/min, respectively. Cardiac arrhythmias were detected during 2 procedures.  In one elephant paroxysmal ventricular tachycardia was detected and the procedure terminated when the arrhythmia failed to stabilize after multiple doses of lidocaine (1 mg/kg, IV).  In another elephant, second degree atrioventricular block returned to normal sinus rhythm after IV administration of atropine (0.04 mg/kg). In one elephant, low mean blood pressure (54 mm of Hg) responded to reduction in halothane (vaporizer setting 1 to 0.75%) and slow infusion of dobutamine HCl ((250 mg/1,000 ml) given to effect. The systolic blood pressure increased to 90 mm of Hg and remained high with a continuous infusion of dobutamine (5 µg/kg/min). Immediately after induction in another elephant, profound respiratory depression (< 1 breath / minute) and palpably weak arterial pulse were identified.  Intravenous administration of diprenorphine at half the recommended reversal dose resulted in improvement of respiration and palpable arterial pulse, without the elephant developing signs of complete anesthetic reversal. Alterations in systolic blood pressure, ear flapping, and trunk muscle tone were useful for monitoring depth of anesthesia.  Results indicated that halothane in oxygen was effective for maintenance of surgical anesthesia in juvenile African elephants after induction with etorphine.  Note: A correction appeared in a later volume 193(6): p.721.

Jacobson, E.R., Kollias, G.V., Heard, D.J., Caligiuri, R., 1988. Immobilization of African elephants with carfentanil and antagonism with nalmefene and diprenorphine. Journal of Zoo and Wildlife Medicine 19, 1-7.
Abstract: Sixteen African elephants (Loxodonta africana) were immobilized with single i.m. injections of carfentanil citrate (2.1 ± 0.3 µg/kg body weight).  All elephants were laterally recumbent in 10.1 ± 3.7 min.  An additional elephant which received 1.4 µg /kg carfentanil did not become recumbent and additional carfentanil was required for immobilization.  Following immobilization, nine elephants were maintained in lateral recumbency by administration of multiple i.v. injections of carfentanil, one elephant received a single i.v. dose of ketamine hydrochloride, and four were intubuted and administered 1-1.5% halothane in oxygen.  Because a short duration of immobilization was desired, three elephants were not given additional drugs.  The duration of immobilization ranged from 4 to 187 min.  Following a variety of medical and surgical procedures, 13 elephants received nalmefene hydrochloride, two elephants received diprenorphine, and two elephants received both diprenorphine and nalmefene; antagonists were administered either i.v. and i.m. or i.v. and s.c.  Sixteen of 17 elephants were standing in 2.9 ± 1.4 min; the standing time of one elephant was not recorded.

Jacobson, E.R. Chemical restraint and anesthesia of elephants. Proc.Ann.Elephant Workshop 9.  112-119. 1988.
Ref Type: Conference Proceeding

Li, C.X., Rong, Y.M., Lan, J.G., 1988. Anthelmintic efficacy of albendazole against parasites in Indian elephants. Chinese Journal of Veterinary Science and Technology 9, 42-43.
Abstract: 4 Indian elephants treated orally with albendazole at 20, 30 or 35 mg/kg were negative for nematode and trematode eggs after one month.

Mihm, F.G., Machado, C., Snyder, R., 1988. Pulse oximetry and end-tidal CO₂ monitoring of an adult Asian elephant. Journal of Zoo and Wildlife Medicine 19, 106-109.
Abstract: The adequacy of ventilation during etorphine anesthesia of a 20-yr-old Asian elephant (Elephas maximus) was monitored with a pulse oximeter to measure arterial hemoglobin oxygen saturation (SaO₂) and a CO₂ analyzer to measure end-tidal CO₂ concentrations (PetCO₂).  Immediately after the first anesthetic induction, SaO₂ values of 45% were noted while the animal was breathing room air at a rate of 6/min.  The SaO₂ readings increased to 93% 15 min after administration of 5 liters/min of oxygen via the trunk.  Seven arterial blood gas samples obtained during two anesthetics, and once while unanesthetized, provided PaO₂ and PaCO₂ values which compared favorably with SaO₂ and PetCO₂.  In the anesthetized animal, PaO₂ ranged between 31 and 70 mmHg while SaO₂ values were 70-95%.  At the same time, measurements of PaCO₂ ranged from 42 to 57 mmHg while values of PetCO₂ ranged from 35 to 57 mmHg.  Pulse oximetry and end-tidal CO₂ monitoring are easy to apply and should increase the safety of anesthesia for these animals.

Jacobson, E.R., Heard, D.J., Caligiuri, R., Kollias, G.V. Physiologic effects of etorphine and carfentanil in African elephants. Proc.1st.Intl.Conf.Zool.Avian Med.  525-527. 1987.
Ref Type: Conference Proceeding
Abstract: Full text: The effects of etorphine hydrochloride and carfentanil citrate on blood pressure, heart rate, respiration and body temperature were determined in a group of captive African elephants (Loxodonta africana).  Fourteen African elephants, weighing 450 kg to 4000 kg, divided into 2 groups of 6 and 8 elephants each, received either etorphine hydrochloride (2.9 ± 0.7 µg/kg of body weight; mean ± SD) or carfentanil citrate (2.0 ± 0.2 µg/kg of body weight) respectively. The mean time for lateral recumbency in elephants which received etorphine was 31 ± 9.1 minutes while the mean time for lateral recumbency in elephants which received carfentanil was 10.3 ± 4.1 minutes.  Following immobilization, a 18 gauge catheter was inserted into an auricular artery, the catheter connected to a pressure transducer system and systolic, diastolic, and mean arterial pressures were monitored by use of a multichannel oscilloscope.  Systolic, diastolic, mean arterial pressures, heart rate, respiration, and temperature were recorded every 5 minutes over a 45 to 60 minute period.  Elephants were maintained in lateral recumbency over the period of monitoring by intravenous injections of either etorphine or carfentanil.  

Following immobilization with etorphine, mean physiological values for elephants were: systolic pressure, 229 ± 33 mm Hg; diastolic pressure, 141 ± 30 mm Hg; mean arterial pressure, 177 ± 30 mm Hg; heart rate 64 ± 10 beats/minute; respiratory rate 10 ± 4 breaths/minute; body temperature, 97 ± 2°F.  Mean physiological values at the final time period of monitoring prior to antagonism were: systolic pressure, 217 ± 40 mm Hg; diastolic pressure, 147 ± 36 mm Hg; mean arterial pressure, 176 ± 38mm Hg; heart rate 77 ± 13 beats/minute; respiratory rate 12 ± 1 breaths/minute; body temperature, 98 ± 2°F.  Immediately following the last recording, all 8 elephants received the experimental opioid antagonist, nalmefene hydrochloride, administered at 38 ± 11 µg/kg of body weight given both subcutaneously and intravenously.  The mean standing time following administration of nalmefene was 1.4 ± 0.7 minutes.

Immediately following immobilization with carfentanil, mean physiological values for elephants were: systolic pressure, 232 ± 28 mm Hg; diastolic pressure, 148 ± 14 mm Hg; mean arterial pressure, 183 ± 24 mm Hg; heart rate 57 ± 11 beats/minute; respiratory rate 11 ± 3 breaths/minute; body temperature, 99 ± 1°F.  Mean physiological values at the final time period of monitoring prior to antagonism were: systolic pressure, 224 ± 29 mm Hg; diastolic pressure, 146 ± 13 mm Hg; mean arterial pressure, 179 ± 18mm Hg; heart rate 65 ± 11 beats/minute; respiratory rate 12 ± 1 breaths/minute; body temperature, 99 ± 1°F. Immediately following the last recording, all 6 elephants received the opioid antagonist, nalmefene hydrochloride administered at 62 ± 17 µg/kg of body weight given both subcutaneously and intravenously.  The mean standing time following administration of nalmefene was 2.6 ± 1.6  minutes. The results of this study indicated that both etorphine and carfentanil resulted in high blood pressure over the duration of the period of monitoring.  Based upon these findings, both etorphine hydrochloride and carfentanil citrate are not recommended as the primary agent in performing major invasive surgical procedures in African elephants.

Limpoka, P., Chai Anan, S., Sirivejpandu, R., Kanchanomai, R., Rattanamonthianchai, S., Puangkum, P., 1987. Plasma concentrations of oxytetracycline in elephants following intravenous and intramuscular administration of Terramycin/LA injectable solution. ACTA VET. BRNO 56, 173-179.
Abstract: The blood concentrations of oxytetracycline were studied in Asian elephants following the intravenous and intramuscular administration of Terramycin/LA solution. The drug was administered as 200 mg of oxytetracycline base/ml in aqueous 2-pyrrolidone at a dose of 20mg/kg body mass.  The blood samples were collected from the ear veins of each animal.  Plasma concentrations of oxytetracycline were analyzed by microbiological method and high pressure liquid chromatography. An average peak plasma concentration of 6.2 ug/ml was obtained in one hour following intravenous administration in elephants No oxytetracycline was detected in plasma after the 60th post dosing hour. The average peak plasma concentration of 2.87 ug/ml was found in two hours following intramuscular administration of the drug.  Concentrations exceeding 1 ug/ml were maintained for 48 hours after intramuscular dose.  The drug was shown to result in sustained oxytetracycline blood concentrations over a three-day period following a single intramuscular administration of the drug to elephants.

Heard, D.J., Jacobson, E.R., Brock, K.A., 1986. Effects of oxygen supplementation on blood gas values in chemically restrained juvenile African elephants. Journal of the American Veterinary Medical Association 189, 1071-1074.
Abstract: Arterial oxygen and carbon dioxide tensions were determined in sedated immature African elephants and in elephants immobilized with etorphine hydrochloride or with an etorphine-ketamine combination.  For manipulative and surgical procedures, the Hudson demand value was used for oxygen supplementation during 6 procedures, and insufflation was used during 2 procedures.  The Hudson demand value was more effective than insufflation in sustaining adequate arterial oxygenation.

Lateur, N., Stolk, P. Repeated general anesthesia in a male Indian elephant. Proc.Am.Assoc.Zoo Vet.  128-131. 1986.
Ref Type: Conference Proceeding

Schmidt, M.J., 1986. Proboscidea (Elephants). In: Fowler, M.E. (Ed.), Zoo and wild animal medicine. W.B. Saunders, Philadelphia,PA, USA, pp. 884-923.

Byron, H.T., Olsen, J., Schmidt, M.J., Copeland, J.F.Jr., Byron, L., 1985. Abdominal surgery in three adult male Asian elephants. Journal of the American Veterinary Medical Association 187, 1236-1237.

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.

Kock, N., Kock, M., Arif, A., Wahid, M.N.S.A. Immobilization techniques and complications associated with a bull Indian elephant (Elephas maximus indicus) during musth. Proc.Am.Assoc.Zoo Vet.  68-74. 1984.
Ref Type: Conference Proceeding

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

Siegel, R.K., 1984. LSD-induced effects in elephants: comparisons with musth behavior. Bulletin of the Psychonomic Society 22, 53-56.
Abstract: Musth is a condition observed in male Asiatic elephants and is characterized by aggression and temporal gland secretion.  A classic and controversial 1962 study attempted to induce a musth syndrome in an elephant via treatment with LSD. Two elephants in the present study survived dosages of LSD (.003 -.10 mg/kg) and exhibited changes in the frequency or duration of several behaviors as scored according to a quantitative observational system.  LSD increased aggression and inappropriate behaviors such as ataxia.  Results are discussed in terms of musth and drug-induced perceptual-motor dysfunction.

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.

Chandrasekharan, K., Cheeran, J.V., Nair, K.N.M., Ramanujam, K.N., Radhakrishnan, K., 1982. Comparative efficacy of 6 anti-helminthics against strongylosis in elephants. Kerala Journal of Veterinary Science 13, 15-20.
Abstract: Infections with Murshidia falcifer, Quilonia travancra and Bathmostomum sangeri in 30 elephants were successfully treated by oral administration (in bread) of mebendazole at 3-4 mg/kg body weight, levamisole at 3 mg/kg and morantel tartrate at 5 mg/kg. Slightly less effective (68-96%  reduction in faecal egg counts) were mebendazole at 2 mg/kg, thiabendazole   [tiabendazole] at 32 mg/kg, bephenium hydroxynaphthoate at 25 mg/kg and  disophenol at 3 mg/kg.

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.

Fowler, M.E., 1981. Problems with immobilizing and anesthetizing elephants. Proceedings American Association of Zoo Veterinarians 87-91.

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

Cheeran, J.V. Chemical control of elephants. State Level Workshop on Elephants.  69-73. 1979. India, College of Veterinary and Animal Sicences, Kerala Agricultural University.
Ref Type: Conference Proceeding

Bongso, T.A., Perera, B.M.A.O., 1978. Observations on the use of etorphine alone and in combination with acepromazine maleate for immobilization of aggressive Asian elephants (Elephas maximus). Veterinary Record 102, 339-340.

de Vos, V., 1978. Immobilization of free-ranging wild animals using a new drug. Vet Rec 103, 64-68.
Abstract: Field trials were conducted with the potent morphine-like analgesic, R33799 (Janssen Pharmaceutica; Beerse, Belgium) in South African national parks on 217 free-ranging wild animals, representing 20 different species. The drug was found to be effective and safe for a wide range of ungulates and pachyderms and Burchell's zebra (Equus burchelli) did not react to expected dosage levels. A suggested dosage regime for 19 species is given.  Recommended optimal dosage rates varies from about 1 microgram per kg for pachyderms to about 10 microgram per kg for most of the larger ungulates. Xylazine and azaperone were found valuable adjuncts to R33799 in dosage ratios of 10:1 and 30:1 respectively.

Schmidt, M.J., 1978. Penicillin and amoxicillin in elephants:  A study comparing dose regimens administered with serum levels achieved in healthy elephants. Journal of Zoo and Wildlife Medicine 9, 127-136.
Abstract: Several dose regimens of an aqueous suspension of benzathine penicillin G combined with procaine penicillin G, and an aqueous suspension of amoxicillin were administered to five healthy adult female Asian elephants.  Blood samples were drawn and serum levels of the drugs were measured after each dose was administered.  Based upon serum levels, suggestions are made for therapeutic dose regimens for clinical use of both penicillin and amoxicillin in elephants, based on comparable data available for other large domestic animals.

von Richter, W., Drager, N., Patterson, L., Sommerlatte, M., 1978. Observations on the immobilization and marking of African elephants (Loxodonta africana) in Botswana. Akademie-Verlag 14, 185-191.
Abstract: 58 elephants were successfully immobilized in their natural environment in the Chobe Nation Park and on privately owned farms in Botswana using a drug mixture of etorphine (M99 Reckitt) and acetylpromazine.  The specific antidote cyprenorphine (M285 Reckitt) was used in most cases to resuscitate the animals.  One known mortality occurred.  For the long term monitoring of social organization and long and short term movements collars manufactured from machine belting and fitted with colour codes or symbols proved most satisfactory. Stamping the tusks near the lip provided a permanent marking although not useful for field observation.  Various other marking techniques were tested but were considered unsatisfactory for long term identification.  Various behavioral aspects associated with the immobilizing of elephants are described and discussed.

Longo, L.D., Hill, E.P., 1977. Carbon monoxide uptake and elimination in fetal and maternal sheep. Am. J Physiology 232, 324-330.

Miller, R.M., 1977. Segmental gangrene and sloughing of elephants' ears after intravenous injection of phenylbutazone. Veterinary Medicine Small Animal Clinician 72, 633-637.

Silberman, M.S., 1977. Tranquilization of the African elephant (Loxodonta africana Blumenbach) with neuroleptic azaperone (R-1929). Journal of Zoo and Wildlife Medicine 8,  7-8.

Longo, L.D., 1976. Carbon monoxide effects on oxygenation of the fetus in utero. Science 19, 523-525.

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.

Ebedes, H., 1975. The immobilization of adult male and female elephant, Loxodonta africana, with etorphine and observation on the action of diprenorphine. Madogua 9, 19-24.

Subramaniam, A., Purushothaman, S., 1975. A case of hypohyon keratitis in an elephant. Madras Veterinary College Annual 33, 15-16.

Alford, B.T., Burkhart, R.L., Johnson, W.P., 1974. Etorphine and diprenorphine as immobilizing and reversing agents in captive and free-ranging mammals. Journal of the American Veterinary Medical Association 164, 702-705.
Abstract: Summary:  Etorphine, an opium alkaloid derivative of thebaine, and its specific antagonist, diprenorphine, were evaluated by research workers and zoo veterinarians in captive and free-ranging animals.    An intramuscular injection of etorphine usually resulted in rapid immobilization, sedation, analgesia, and muscle relaxation in Equidae, Ursidae, Cervidae and Bovidae, when given at a rate of 0.44, 0.5, 0.98 and 1.09 mg/45 kg (100 lb.), respectively. Satisfactory immobilization was usually achieved within 5 to 15 minutes after intravenous administration of diprenorphine at twice the etorphine dosage.    Procedures performed after etorphine administration included dehorning, blood sampling, tail docking, antibacterial injection, radiography, orthopedic surgery, and obstetrical manipulation.    Side effects were commonly noticed in free-ranging mammals. The type and degree of reaction varied according to the species and included tachycardia, bellowing, bradycardia, respiratory depression, opisthotonos, muscular tremors, mydriasis, and hyperpyrexia.  Of 1,600 animals tested, 2.9% died as a result of severe heat prostration, inhalation pneumonia, respiratory depression, severe excitement due to underdosing, cardiac arrest, and inapparent disease.

Nair, K.P.D., Chandrasekharan, K., Menon, M., 1972. Chloropromazine toxicity in an elephant. Kerala Journal Veterinary Science 3, 102-106.

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.

West, L.J., Pierce, C.M., 1962. Lysergic acid diethylamide: Its effects on a male Asiatic elephant. Science 138, 1100-1103.
Abstract: Summary:Researchers gave LSD to a zoo elephant in order to "induce a behavioral abberation that might resemble the phenomenon of going on musth."  Elephant cause of death was asphixiation secondary to laryngeal spasm.

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

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.

Counsilman, J.W., 1954. Demerol hydrochloride as an anesthetic for an elephant. North American Veterinarian 35, 835-836.

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.

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

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

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

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

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.

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

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

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