Elephant
Bibliographic
Database

.

...

Elephant Bibliographic Database
www.elephantcare.org

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

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

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

Miller, M.A., Olea-Popelka, F., 2009. Serum antibody titers following routine rabies vaccination in African elephants. Journal of the American Veterinary Medical Association 235, 978-981.
Abstract: Objective-To evaluate serum antibody titers in captive African elephants (Loxodonta africana) following routine vaccination with a commercially available, inactivated rabies vaccine. Design-Seroepidemiologic study. Animals-14 captive African elephants from a single herd. Procedures-Elephants were vaccinated as part of a routine preventive health program. Initially, elephants were vaccinated annually (2 mL, IM), and blood was collected every 4 or 6 months for measurement of rabies virus-neutralizing antibody titer by means of the rapid fluorescent focus inhibition test. Individual elephants were later switched to an intermittent vaccination schedule to allow duration of the antibody response to be determined. Results-All elephants had detectable antibody responses following rabies vaccination, although there was great variability among individual animals in regard to antibody titers, and antibody titers could be detected as long as 24 months after vaccine administration. Young animals were found to develop an antibody titer following administration of a single dose of the rabies vaccine. Age and time since vaccination had significant effects on measured antibody titers. Conclusions and Clinical Relevance-Results indicated that African elephants developed detectable antibody titers in response to inoculation with a standard large animal dose of a commercially available, inactivated rabies vaccine. The persistence of detectable antibody titers in some animals suggested that vaccination could be performed less frequently than once a year if antibody titers were routinely monitored

Fowler, M.E. Wound healing in elephants. Proc American Associaton of Zoo Veterinarians and Assoc of Reptile and Amphibian Veterinarians.  143-144. 2008. 11-10-2008.
Ref Type: Conference Proceeding
Abstract: Basic Wound Healing
A wound into the subcutaneous tissue follows sequential stages of healing, namely inflammation, débridement, proliferation, epithelization and contraction (scarring). Elephant wounds go through the same sequences if allowed to do so. Basic mammalian wound healing involves the epidermis, germinal epithelium, dermis and subcutaneous tissue. In the elephant foot the
epidermis becomes the cornified sole, pad or nail, which is produced by the germinal epithelium.The dermis becomes the corium (vascularized fibrous tissue connecting the cornified shell to the digits). The healing process may take weeks, months and even years. Particular emphasis will be given to anatomy as it relates to foot infections, basic principles of wound healing in mammals as applied to elephants, predisposing factors and factors that inhibit wound healing. Predisposing Factors of Foot Infections
Genetics (conformation defects), malnutrition (rickets), abnormal behavior (stereotypy, pawing, resting with pressure on a specific area of the foot, excessive pressure to compensate for pain in another limb), degenerative joint disease, poor sanitation, no variation in the enclosure substrate, and minimal opportunity to exercise are such factors.
Cardinal Rules Governing Wound Management, Specifically Foot Infections
 1. Elephants should be trained to allow foot inspection of all feet on a daily basis.
2. Minimize or eliminate predisposing factors.
3. Remove all necrotic material, dirt, feces, urine and debris from the wound cavity.
4. Obtain adequate drainage for an exudate to exit the cavity.
5. Prevent recontamination of the clean wound either by packing the wound cavity with
disinfectant soaked gauze or by applying a protective boot.

Turner, J.W., Rutberg, A.T., Naugle, R.E., Kaur, M.A., Flamagan, D.R., Bertschinger, H.J., Liu, I.K.M., 2008. Controlled-release components of PZP contraceptive vaccine extend duration of infertility. Wildlife Research 35, 555-562.
Abstract: Successful immunocontraception of wildlife relying on repeated access to individuals for boosters has highlighted the need to incorporate primer and booster immunisations into one injection. We have investigated use of controlled-release polymers (lactide-glycolide) in small pellets to provide delayed in vivo delivery of booster porcine zona pellucida (PZP) antigen and adjuvant. This report reviews pellet-making methodology, in vitro testing of controlled-release pellets and in vivo effects of controlled-release PZP vaccine. We assessed 3 different manufacturing approaches for producing reliable, cost-effective pellets: (1) polymer melting and extrusion; (2) solvent evaporation from polymer solution; and (3) punch and die polymer moulding. In vitro testing of release patterns of controlled-release formulations, towards development of a 3-year duration vaccine, provided estimates for in vivo use of pellet preparations. These in vitro studies demonstrated protein release delay up to 22 months using 100% l-lactide or polycaprolactone polymers. For in vivo tests, pellets (1-, 3-, and 12-month release delay) serving as boosters were administered intramuscularly with PZP/adjuvant liquid primer to wild horses (Equus caballus), white-tailed deer (Odocoileus virginanus) and African elephants (Loxodonta africana). Horse. field studies assessed fertility via offspring counts and/or faecal-hormone pregnancy testing. Treatment decreased fertility 5.3-9.3-fold in Year 1 and 3.6-fold in Year 2. In preliminary testing in deer, offspring counts revealed treatment-associated fertility reduction of 7.1-fold Year 1 and 3.3-fold Year 2. In elephants, treatment elevated anti-PZP titres 4.5-6.9- fold from pretreatment (no fertility data).

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.

Bertschinger, H., Delsink, A., Kirkpatrick, J.F., Human, A., Grobler, D., van Altena, J.J. Management of elephant populations in private South African game reserves with porcine zona pellucida vaccine.  2006 Proceedings American Association of Zoo Veterinarians.  283-285. 2006.
Ref Type: Conference Proceeding
Abstract: Control of African elephant populations has become an absolute necessity in a number of game reserves in southern Africa.  The two main methods used to control populations so far are culling and translocation. Culling, besides being regarded as inhumane and unacceptable in many quarters, is not suitable for smaller populations.  It requires that whole family units are culled simultaneously which could mean that in reserves with 10 to 50 elephants a considerable portion, if not the entire population, is killed.  As far as translocation is concerned, limited new space is available for elephants. The only alternative to the two above options is to control the rate of reproduction. The porcine zona pellucida (pZP) vaccine has been used to successfully contracept wild horses and other wildlife species.  Work on the contraception of African elephants was initiated in the Kruger National Park in 1995 when the potential for using the porcine zona pellucida (pZP) was investigated. Subsequently the first field trials on wild elephants were carried out in Kruger and the results clearly showed that elephants could be contracepted with the pZP vaccine, although the efficacy achieved was 80%. During these field trials safety and reversibility werecould be demonstrated. In 2000 an elephant contraceptive program was initiated at Makalali Private Game Reserve, RSA, which has become the flagship model for immunocontrol in African elephants. The preliminary findings have been reported in three publications.During the first year, all 18 cows that were individually identified and older than 12 yr of age were treated.  During the next 4 yr the number of cows contracepted increased to 23 as young animals were added to the program. The standard vaccination procedure during the first year consisted of a primary vaccination (600 μg or 400 μg pZP with 0.5 ml Freund's modified complete adjuvant) followed by boosters (200 μg pZP with 0.5 ml Freund's incomplete adjuvant) at 3 to 6-wk intervals. Annual boosters to maintain antibody titers and contraceptive effect followed.  To date, the success rate on cows that have passed reserve-specific intercalving period of 56 mo has been 100%. The population stabilized within 3 yr by which time when all cows that had been pregnant at the time of first vaccination in 2000 had calved. Once again safety during pregnancy (14 cows pregnant at 2-21 mo gestation when first treated gave birth to normal healthy calves) as well as side effects that were limited to occasional lumps at the site of vaccination could be shown. Following ground darting, behavioral patterns returned to pre-darting status within 2 days. During 2003 and 2004 most boosters were administered from a helicopter; whereas, previously they had been done from a vehicle or on foot.  In all cases, drop-out darts were used. Time taken for vaccination from helicopter take-off to landing was about 30 min (1.5 min per cow; 30 min for total time). This required prior knowledge of the locations of family units or that an individual in each unit is radio-collared. Herds settled down much more quickly (1-2 days) than if darted from the ground. Since then we have vaccinated another 107 elephant cows in eight game reserves.  The cow populations have ranged from 4 to 43. In one of the reserves, Mabula, RSA, two of the four cows vaccinated have passed the mean intercalving intervals of the reserve with neither of them producing a calf. Treatment at the remaining reserves was initiated in 2004 or 2005 and it is too early to evaluate results.  The most difficult reserve in terms of the vaccination process was Welgevonden, RSA, (35 000 ha) with 43 cows.  The reserve is mountainous and heavily wooded. None of the elephants were collared and individuals could not be easily identified on the day of primary vaccination.  The total flying time during which individuals were identified and vaccinated was 4.5 hr.  Administration of the first booster took about 2 hr to locate and vaccinate each cow. Between the first and second booster the first rains occurred, followed by the spring flush of the vegetation. By the time the second booster was attempted late in November, the trees all had foliage. Only half the cows were located and darted because the elephants were very difficult to spot under the tree canopies.  The valuable lessons we learned from this were: 1) that helicopter vaccinations should be performed when most trees are bare, and 2) when larger populations are vaccinated repeatedly during the first year, one cow in each family unit should be radio-collared. This makes rapid location of each unit possible and cuts down on the major cost factor that is flying time. Elephant behavior is being monitored in all eight reserves where contraception is being applied. Because most of them have been contracepted recently, only the data from Makalali is available. The elephants at Makalali have been monitored intensively almost on a daily basis. To date, no anomalies in terms of aggressive or indifferent behavior with regards to nursing time, nursing behavior and calf proximity have been noted. No change in the cows' social hierarchy has been noted. Since January 2003, a total of 15 heats were observed in 10 cows (nine in 2003 and six in 2004) with four mating episodes. For the same period, 38 musth occasions were seen in five bulls (26 in 2003 and 12 in 2004). These occasions include musth displayed in the same bull during consecutive days or within the same musth cycle. The greatest occurrence of musth was recorded in the largest, dominant bull. Bulls were not observed harassing or separating cows off from their herds or calves as a result of increased estrous frequency. Thus, the Makalali program demonstrates that pZP does not cause herd fragmentation, harassment by bulls, change in rank and other negative behaviors normally associated with hormonal contraceptives. In conclusion we feel that it is important to emphasize the following points: The pZP vaccine can be used successfully to contracept African elephants The vaccine is safe during pregnancy and has no negative effect on birth or calf raising It has no side effects other than occasional swelling at the site of vaccination It is reversible Other than an increased incidence of heat no behavioral side effects were seen.

Delsink, A.K., van Alten, J.J., Grobler, D., Bertschinger, H., Kirkpatrick, J., Slotow, R., 2006. Regulation of a small, discrete African elephant population through immunocontraception in the Makalali Conservancy, Limpopo, South Africa. South African Journal of Science 102, 403-405.
Abstract: Populations of the African elephant, Loxodonta africana, are growing rapidly in southern Africa, to the extent that population control has become essential. The management option of translocation is no longer realistically available, whilst culling has become ethically unacceptable, especially to the general public. Previous immunocontraception trials on elephants with Porcine Zona Pellucida (PZP) vaccine demonstrated that it is safe, effective, reversible, remotely deliverable, and has had no evident adverse side effects. We demonstrate effective contraceptive management of a discrete, small population of free-roaming elephants in the Makalali Conservancy, Limpopo province, South Africa. Complete reproductive control has been demonstrated in all 18 original targeted females, who have by now passed the population's average intercalving interval of 56 months without giving birth. A zero population growth rate has been maintained within this target group since August 2002. On the basis of this small sample over a short period, immunocontraception should be considered a viable means of population management as an alternative to long-term culling strategies in small populations

Fraunfelder, F.T., Finnegan, M., Wilson, D.J., 2006. Conjunctival-corneal intraepithelial neoplasm in an Asian elephant (Elephas maximus). J. Zoo. Wildl. Med. 37, 424-426.
Abstract: An adult female Asian elephant (Elephas maximus) presented with an enlarging nasal limbal mass of the left eye. The mass was excised and the surgical bed treated with liquid nitrogen cryotherapy. Histopathologic examination of the excised tissue showed the mass to be a superficial dysplastic ocular lesion, or conjunctival intraepithelial neoplasm. A 5-yr follow-up period has passed without complications or recurrence, suggesting that as is the case in humans (Homo sapiens), excision and cryotherapy is an effective treatment for these lesions in elephants. This is the first report of any ocular neoplasia in an elephant

Isaza, R., Davis, R.D., Moore, S.M., Briggs, D.J., 2006. Results of vaccination of Asian elephants (Elephas maximus) with monovalent inactivated rabies vaccine. American Journal of Veterinary Research 67, 1934-1936.
Abstract: OBJECTIVE: To evaluate the humoral immune response of Asian elephants to a primary IM vaccination with either 1 or 2 doses of a commercially available inactivated rabies virus vaccine and evaluate the anamnestic response to a 1-dose booster vaccination. ANIMALS: 16 captive Asian elephants. PROCEDURES: Elephants with no known prior rabies vaccinations were assigned into 2 treatment groups of 8 elephants; 1 group received 1 dose of vaccine, and the other group received 2 doses of vaccine 9 days apart. All elephants received one or two 4-mL IM injections of a monovalent inactivated rabies virus vaccine. Blood was collected prior to vaccination (day 0) and on days 9, 35, 112, and 344. All elephants received 1 booster dose of vaccine on day 344, and a final blood sample was taken 40 days later (day 384). Serum was tested for rabies virus-neutralizing antibodies by use of the rapid fluorescent focus inhibition test. RESULTS: All elephants were seronegative prior to vaccination. There were significant differences in the rabies geometric mean titers between the 2 elephant groups at days 35, 112, and 202. Both groups had a strong anamnestic response 40 days after the booster given at day 344. CONCLUSIONS AND CLINICAL RELEVANCE: Results confirmed the ability of Asian elephants to develop a humoral immune response after vaccination with a commercially available monovalent inactivated rabies virus vaccine and the feasibility of instituting a rabies virus vaccination program for elephants that are in frequent contact with humans. A 2-dose series of rabies virus vaccine should provide an adequate antibody response in elephants, and annual boosters should maintain the antibody response in this species

Weidner, E.B., Isaza, R., Galle, L.E., Barrie, K., Lindsay, W.A., 2006. Medical management of a corneal stromal abscess in a female Asisan elephant (Elephas maximus). Journal of Zoo and Wildlife Medicine 37, 397-400.

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.

Delves, P.J., Roitt, I.M., 2005. Vaccines for the control of reproduction--status in mammals, and aspects of comparative interest
592. Dev. Biol. (Basel) 121, 265-273.
Abstract: The objective of producing vaccines which target elements of the reproductive system to control fertility has been pursued for many years. Of the many targets for such vaccines, several sperm-associated antigens have been proposed for antibody-mediated intervention before fertilization but the very abundance of antigen to be neutralized has been a barrier. Zona pellucida antigens associated with the surface of the oocyte have also been targeted and used successfully for control of 'wild' elephant populations but worries concerning immunopathologically-mediated tissue damage have been mooted. Vaccines using human chorionic gonadotropin (hCG) which is required for the implantation and maintenance of the fertilized egg, although of interest for the development of fertility control in human populations, has no relevance in the context of the present conference because external fertilization of fish eggs is independent. The pathways by which gonadotropin-releasing hormone (GnRH) secreted by the hypothalamus promote release of luteinizing (LH) and follicle-stimulating hormone (FSH) which govern the physiological maturation and maintenance of the reproductive organs, provide many targets for immunological intervention. Most consistent success has been reported using GnRH-based vaccines which are immunosterilizing in a variety of mammalian species such as pigs, rodents and white-tailed deer. The fact that the structure of the decapeptide, GnRH, has been maintained over so many years of evolution and been conserved across so many animal species, encourages the view that a strategy for control of sexual maturation in fish based upon stimulation of GnRH antibodies may well prove to be a practical proposition, provided the formulation of an appropriate highly immunogenic vaccine can be achieved

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.

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.

Panzer, R., 2005. Traditional Chinese veterinary medical therapy. In: Colahan, P.T., Merritt, A.M., Moore, J.N., Mayhew, I.G. (Eds.), Equine Medicine and Surgery. Mosby, St. Louis MO USA, pp. 201-208.

Rush, E.M., Brawner, W.R., Ogburn, A.L., Marshall, A., Hathcock, J.T. Comparison of radiographs versus computed tomography evaluation of the distal limb in an Asian elephant. 2005 Proceedings AAZV, AAWV, AZA Nutrition Advisory Group.  68-69. 2005.
Ref Type: Conference Proceeding
Abstract: Feet problems are the most commonly seen ailment in captive elephants.  In the field of zoo and wildlife medicine, radiographs are the accepted standard of skeletal evaluation of the distal limb of elephants, to show changes in bone density and conformation .¹ Although radiographs are considered reliable to show severe degenerative change in the distal phalanges, it is difficult to assess detail of the carpus and tarsus due to the anatomy and superimposition of the large carpal and tarsal bones. Radiographic images of the distal limbs of a geriatric, female Asian elephant, were compared with postmortem computed tomography (CT) images.  This animal had a long history of clinical nail disease treated for many years with diligent foot care and aggressive paring of multiple nails. Arthritis of the carpi, tarsi and/or digits was suspected and had been treated with non-steroidal anti-inflammatory medications. Serial radiographs from several years showed obvious degenerative change in multiple digits, especially those most severely affected clinically at the nail. Osseous detail in the carpi and tarsi was suboptimal on radiographs even when postmortem specimens were radiographed with a stationary, high capacity radiograph machine designed for large animal radiology.  CT images of the distal limbs revealed degenerative skeletal changes that were not readily apparent on radiographs.  Most degenerative change was noted in the periosteal areas of the carpal and tarsal bones, particularly at articular surfaces. Realizing that CT of feet and distal limbs of live elephants is impractical, if not impossible, this comparison of radiographs and CT demonstrates that radiographs may not reveal all abnormalities present in joints of the distal extremities. Comparative CT images of younger or clinically normal animals were not available, so it has not been possible to determine the clinical significance of the apparent degenerative changes noted on these radiographs and CT images at the time of this publication.  Nonetheless, consideration should be given for the lack of detail when evaluating radiographs of elephant feet. When radiographic changes are noted in the distal limbs of elephants suffering from arthritis with a history of nail disease, the attending veterinarian may consider prophylactic antibiotic therapy to treat possible osteomyelitis in the bones of the distal limb.  Also, in animals with arthritic change on radiographs and no nail disease, implementation of appropriate antiinflammatory drugs and/or joint supplements should be considered.  Hydrotherapy, acupuncture, limb exercise and other topical therapies may be warranted, depending on each individual case and the clinical signs exhibited. Routine and diagnostic radiographs should be taken from several angles, including oblique views, to assure the most accurate assessment of bony change in the distal limb and to give the best overall images for retrospective comparison. Radiographs should include the carpus and tarsus if the radiograph machine has the capacity for the bone density of that region.
ACKNOWLEDGMENTS
Thanks to the State Veterinary Diagnostic Laboratory, Auburn University College of Veterinary Medicine Department of Radiology for all of their time, expertise and contributions to this study.  Also, thanks to Marcia Riedmiller and the pachyderm care staff at the Birmingham Zoo.
LITERATURE CITED
1.Fowler, M.E., and R.E. Miller. 2003. Zoo and Wild Animal Medicine, 5th Edition. St. Louis: Elsevier Science. Pp 547-548.

Xie, H., Colahan, P., Ott, E.A., 2005. Evaluation of electroacupuncture treatment of horses with signs of chronic thoracolumbar pain. Journal of the American Veterinary Medical Association 227, 281-286.

Principles of validation of diagnostic assays for infectious diseases.  2004.
Ref Type: Electronic Citation

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

Priyadarshini, S., 2004. Hastiayurveda - an ancient treatise on elephant health care. Science India 7, 79-81.

Sarma, K.K., 2004. Extraction of decayed tusk in elephants. Indian Veterinary Journal 81, 812-814.
Abstract: Case history of dental pulp decay in eight male Asian elephants is discussed. Causes of injury and infection, pathological process and clinical signs are elaborated. Treatment of the cases by extraction of the decayed tusks, anaesthetic management, operative procedure, post operative care and the outcome of treatment has been discussed.

Seidon, A., Hine, E.A.S., 2004. Acupuncture treatment on a female Asian elephant with trunk paralysis. Science India 9 and 10, 82-85.

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.

Xie, H. How to use acupuncture for elephants. The North American Veterinary Conference.  1457-1458. 2004.
Ref Type: Conference Proceeding

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.

Hunter, R.P., Isaza, R., Koch, D.E., 2003. Oral bioavailability and pharmacokinetic characteristics of ketoprofen enantiomers after oral and intravenous administration in Asian elephants (Elephas maximus). American Journal of Veterinary Research 64, 109-114.
Abstract: OBJECTIVE: To assess oral bioavailability (F) and pharmacokinetic characteristics of the R- and S-enantiomers of ketoprofen administered IV and orally to captive Asian elephants (Elephas maximus). ANIMALS: 5 adult Asian elephants. PROCEDURE: Elephants received single treatments of racemic ketoprofen at a dose of 2.2 mg/kg, administered IV and orally, in a complete crossover design. Blood samples were collected at intervals during the 24 hours following treatment. At least 4 weeks elapsed between drug administrations. Samples were analyzed for R- and S-ketoprofen with a validated liquid chromatography-mass spectroscopic assay. Pharmacokinetic parameters were determined by use of noncompartmental analysis. RESULTS: The enantiomers of ketoprofen were absorbed well after oral administration, with median F of 101% for R-ketoprofen and 85% for S-ketoprofen. Harmonic mean half-life ranged from 3.8 to 5.5 hours, depending on route of administration and enantiomer. The area under the concentration-time curve, mean residence time, apparent volume of distribution, plasma clearance, and maximum plasma concentration values were all significantly different between the 2 enantiomers for both routes of administration. CONCLUSIONS AND CLINICAL RELEVANCE: Ketoprofen has a long terminal half-life and complete absorption in this species. Based on the pharmacokinetic data, a dosage of ketoprofen of 1 mg/kg every 48 hours to 2 mg/kg every 24 hours, PO or IV, is recommended for use in Asian elephants, although the safety and efficacy of ketoprofen during long-term administration in elephants have not been determined.

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.

Pitts, N.I., Mitchell, G., 2003. In vitro succinylcholine hydrolysis in plasma of the African elephant (Loxodonta africana) and impala (Aepyceros melampus). Comparative Biochemistry and Physiology C-Toxicology and Pharmacology. 134, 123-129.
Abstract: In elephants the time lapsed from i.m. injection of an overdose of the muscle relaxant succinylcholine (SuCh) until death, is significantly longer than in impala. To determine a difference in the rate of SuCh hydrolysis, once the drug enters the circulation, contributes to this phenomenon we have measured the rate of hydrolysis of SuCh in elephant and impala plasma, and by elephant erythrocytes. Rate of hydrolysis was determined by incubating SuCh in plasma or erythrocyte lysate at 37°C and quantifying the choline produced. Plasma SuCh hydrolytic activity in elephant plasma (12.1±1.7 U/litre, mean±S.D.; n=9) was significantly higher than it was in impala plasma (6.6±0.6 U/litre, n=5), but were approximately 12 and 21 times lower, respectively, than in human plasma. Elephant erythrocyte lysate had no SuCh hydrolytic activity. Applying this data to previous studies, we can show that the ratio of SuCh absorption to SuCh hydrolysis is expected to be 1.25:1 and 1.41:1 for elephants and impala respectively. It will thus take at least 1.7 times longer for elephant to achieve a plasma SuCh concentration similar to that in impala. We conclude that a more rapid hydrolysis of SuCh in elephant plasma is one factor that contributes to the longer time to death compared to impala.

Pitts, N.I., Mitchell, G., 2003. In vitro succinylcholine hydrolysis in plasma of the African elephant (Loxodonta africana) and impala (Aepyceros melampus). Comp Biochem Physiol C Toxicol Pharmacol 134, 123-129.
Abstract: In elephants the time lapsed from i.m. injection of an overdose of the muscle relaxant succinylcholine (SuCh) until death, is significantly longer than in impala. To determine a difference in the rate of SuCh hydrolysis, once the drug enters the circulation, contributes to this phenomenon we have measured the rate of hydrolysis of SuCh in elephant and impala plasma, and by elephant erythrocytes. Rate of hydrolysis was determined by incubating SuCh in plasma or erythrocyte lysate at 37 degrees C and quantifying the choline produced. Plasma SuCh hydrolytic activity in elephant plasma (12.1+/-1.7 Ul(-1) mean+/-S.D.; n=9) was significantly higher than it was in impala plasma (6.6+/-0.6 Ul(-1); n=5), but were approximately 12 and 21 times lower, respectively, than in human plasma. Elephant erythrocyte lysate had no SuCh hydrolytic activity. Applying this data to previous studies, we can show that the ratio of SuCh absorption to SuCh hydrolysis is expected to be 1.25:1 and 1.41:1 for elephants and impala respectively. It will thus take at least 1.7 times longer for elephant to achieve a plasma SuCh concentration similar to that in impala. We conclude that a more rapid hydrolysis of SuCh in elephant plasma is one factor that contributes to the longer time to death compared to impala.

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

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

Steiner, M., Gould, A.R., Clark, T.J., Burns, R., 2003. Induced elephant (Loxodonta africana) tusk removal. Journal of Zoo and Wildlife Medicine 34, 93-95.
Abstract: Elephant tusk removal usually requires costly surgical procedures that are time-consuming and present a significant risk to the animal when performed using general anesthesia. Such techniques require gauges, chisels, and forceps to remove the tusk. This article reports the simple removal of the tusk of an 18-yr-old African elephant (Loxodonta africana) without the use of surgical instruments and anesthesia. Rubber elastics were placed around a tusk, causing loss of alveolar bone with subsequent exfoliation of the tusk within 3 wk. The healing process was uneventful. Department of Surgical and Hospital Dentistry, School of Dentistry, University of Louisville, Louisville, Kentucky 40292, USA.

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

Delsink, A.K., van Altena, J.J., Kirkpatrick, J., Grobler, D., Fayrer-Hosken, R.A., 2002. Field applications of immunocontraception in African elephants (Loxodonta africana). Reprod Suppl 60, 117-124.
Abstract: The primary aim of the Makalali elephant immunocontraception programme is to test the efficacy of porcine zona pellucida (PZP) vaccine for practical population control of elephants in small, enclosed reserves, with the goal of stabilizing the current growth rate and reducing it to the 5-10% per annum displayed currently in the Kruger National Park. A secondary aim is to test the hypothesis that PZP treatment does not affect patterns of elephant social behaviour. Eighteen sexually mature cows (age > 12 years) were vaccinated in May 2000 using remote darts. Behavioural observations before, during and after vaccination included noting the activity of individual animals every minute for 15 min. No changes in general behaviour patterns have been noted to date although the animals' spatial use of the reserve was erratic during the period of vaccination, indicating irregular or disturbed patterns associated with vaccination. Normality was resumed on completion of the vaccinations. No aggressive or indifferent behaviour related to nursing, calf proximity or bull-cow interactions have been noted. Ten of the females were in various stages of pregnancy when treated. Subsequently, seven of them gave birth to healthy calves and the other three females are expected to calve shortly. It is too early in the study to draw conclusions about stabilization of growth rates.

Naveen, P.K., 2002. Homeopathy in elephant practice. Journal of Indian Veterinary Association Kerala 7, 52.

Pitts, N.I., Mitchell, G., 2002. Pharmacokinetics and effects of succinylcholine in African elephant (Loxodonta africana) and impala (Aepyceros melampus). Eur J Pharm Sci 15, 251-260.
Abstract: The phenomenon of slow onset of succinylcholine (Sch) effect in elephants was investigated by analyzing blood concentrations of Sch and its metabolite choline in elephant and impala. To assess whether the slow onset phenomenon is related to the pharmacokinetics of Sch following i.m. administration, we analyzed the time course of plasma concentrations of intact drug and its metabolite and determined its pharmacological effects. Blood samples were obtained from anaesthetized elephant (n=6) and impala (n=7) following i.m. administration of a lethal dose of Sch. Time from Sch injection to onset of apnoea and to death was significantly longer for elephant than impala (mean+/-S.D. apnoea 4.4+/-1.5 and 2.3+/-0.9 min, respectively; death 32.6+/-7.3 and 6.2+/-3.4 min, respectively). The C(max) was not different between elephants and impala (20.3+/-7.9 vs. 14.4+/-6.8 nmol ml(-1), respectively) but the t(max) was significantly longer for elephants (23.0+/-7.6 vs. 3.7+/-2.2 min). Analysis of the plasma Sch and choline concentrations over time revealed that the relative amount of Sch entering the circulation within the first 30 s after i.m. injection is greater for impala than elephant. No greater rate in the plasma hydrolysis of Sch in elephant compared to impala was apparent.

Pitts, N.I., Mitchell, G., Raath, C., 2002. Succinylcholine overdose in the African elephant (Loxodonta africana) and impala (Aepyceros melampus): pharmacokinetics, pharmacodynamics and physiological responses. South African Journal of Science 98, 581-588.
Abstract: We investigated the mechanism of the delayed effect of succinylcholine (SuCh) in elephants, by correlating the plasma concentration of SuCh with alterations in respiratory and cardiovascular function and with changes in plasma markers of metabolism. These changes were compared with those in impalas, following a lethal SuCh dose in each species. Total entry of SuCh into the circulation (cumulative dose) and total exposure of neuromuscular receptors to unhydrolysed SuCh (area under curve of plasma, SuCh vs. time), were determined. Absorption of intramuscular SuCh was slower, and the cumulative dose lower in elephant than impala, but exposure to intact SuCh was similar in both. SuCh produced apnoea, a fall in PaO2 and pH, and rises in the PaCO2 and plasma catecholamine and cortisol concentrations, and variable cardiovascular responses. These changes took longer to develop in elephant than impala, but in both species death was associated with metabolic consequences of severe hypoxia. We conclude that the delayed effect of SuCh in elephant does not arise from differences in SuCh pharmacodynamics between the species but can be attributed to different pharmacokinetics, the lower mass-specific metabolic rate of the elephant, and its greater tolerance of severe metabolic changes before death results.

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

Schaftenaar, W., 2002. Use of vaccination against foot and mouth disease in zoo animals, endangered species and exceptionally valuable animals. Rev. sci. tech. Off. int. Epiz. 21, 613-623.
Abstract: A historical review of foot and mouth disease (FMD) in non-domestic species is given and the use of FMD vaccines to protect those species is described. Several non-domestic species are susceptible to FMD. Legislation in many countries, based on the definition of FMD-free status as determined by the Office International des Epizooties (OIE: World organisation for animal health), forms an important barrier against the use of vaccines. National authorities may even feel obliged to slaughter animals of threatened species protected by international
agreements during an outbreak of FMD to preserve their FMD-free status. The importance of international breeding programmes for endangered species is forcing the international community to reconsider the role that vaccination against FMD should play in animal health prevention programmes of captive populations. Much research is still required in regard to vaccine types and diagnostic procedures. Species-specific differences in susceptibility to FMD make this a challenging research topic for zoological institutions.  Use of vaccination against foot and mouth disease in zoo animals, endangered species and exceptionally valuable animals

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.

Delsink, A.K., van Altena, J.J., Kirkpatrick, J., Grobler, D., Fayrer-Hosken, R. Field applications of immunocontraception in African elephants (Loxodonta africana). Proceedings of the Fifth International Symposium on Fertility Control in Wildlife.  2001.  Society for Reproduction and Fertility; Cambridge; UK. 2001.
Ref Type: Conference Proceeding
Abstract: The primary aim of the Makalali elephant immunocontraception programme is to test the efficacy of porcine zona pellucida (PZP) vaccine for practical population control of elephants in small, enclosed reserves, with the goal of stabilizing the current growth rate and reducing it to the 5-10% per annum displayed currently in the Kruger National Park. A secondary aim is to test the hypothesis that PZP treatment does not affect patterns of elephant social behaviour. Eighteen sexually mature cows (age > 12 years) were vaccinated in May 2000 using remote darts. Behavioural observations before, during and after vaccination included noting the activity of individual animals every minute for 15 min. No changes in general behaviour patterns have been noted to date although the animals' spatial use of the reserve was erratic during the period of vaccination, indicating irregular or disturbed patterns associated with vaccination. Normality was resumed on completion of the vaccinations. No aggressive or indifferent behaviour related to nursing, calf proximity or bull-cow interactions have been noted. Ten of the females were in various stages of pregnancy when treated. Subsequently, seven of them gave birth to healthy calves and the other three females are expected to calve shortly. It is too early in the study to draw conclusions about stabilization of growth rates.

Fowler, M.E., 2001. Elephant foot care: concluding remarks. In: Csuti, B., Sargent, E.L., Bechert, U.S. (Eds.), The Elephant's Foot. Iowa State University Press, Ames, Iowa, USA, pp. 147-149.

Gage, L., 2001. Treatment of osteomyelitis in elephant feet. In: Csuti, B., Sargent, E.L., Bechert, U.S. (Eds.), The Elephant's Foot. Iowa State University Press,  Ames, Iowa, USA, pp. 117-118.

Gibson, K., Flanagan, J.P., 2001. Ouch, do that again! Treatment of chronic nail infections in an Asian bull elephant using protected contact. In: Csuti, B., Sargent, E.L., Bechert, U.S. (Eds.), The Elephant's Foot. Iowa State University Press, Ames, Iowa, USA, pp. 87-88.

Hinke, A., Wipplinger, J. A Severe Case of Pox Disease in Two Asian Elephants (Elephas maximus) of a Small Travelling Circus Overwintering Near Erfurt. A Research Update on Elephants and Rhinos; Proceedings of the International Elephant and Rhino Research Symposium, Vienna, June 7-11, 2001.  53-56. 2001. Vienna, Austria, Schuling Verlag. 2001.
Ref Type: Conference Proceeding
Abstract: A 32 and a 35 year old Asian elephant (Elephas maximus) belonging to a small travelling circus showed symptoms of a severe pox disease in September 2000 during overwintering near Erfurt. From mucous conjunctival excretions and typical lesions of the mucosa of the mouth a poxvirus strain was isolated which showed the biological characteristics of cowpox virus (Orthopoxvirus bovis). Because of the fact that the elephants were treated about 5 weeks the wrong way from another veterinarian who had no experience with pox disease in elephants medical treatment started to became a bit difficult. After weeks of intensive medical care the condition improved, however due to massive cycles of further virus development it deteriorated, and the animals had to be euthanised after about 5 weeks of treatment.

Hinke, A., Wipplinger, J. A Case of Molar Anomalie in an Asian Elephant (Elephas maximus). A Research Update on Elephants and Rhinos; Proceedings of the International Elephant and Rhino Research Symposium, Vienna, June 7-11, 2001.  264. 2001. Vienna, Austria, Schuling Verlag. 2001.
Ref Type: Conference Proceeding

Houser, D., Simmons, L.G., Armstrong, D.L., 2001. Treatment of an abscessed footpad of an African elephant (Loxodonta africana) using a sandal and topically applied chitosan. In: Csuti, B., Sargent, E.L., Bechert, U.S. (Eds.), The Elephant's Foot. Iowa State University Press, Ames, Iowa, USA, pp. 107-113.

Hughes, J., Southard, M., 2001. Elephant Foot Care for an Asian Elephant at Mesker Park Zoo and Botanic Garden. In: Csuti, B., Sargent, E.L., Bechert, U.S. (Eds.), The Elephant's Foot. Iowa State University Press,  Ames, Iowa, USA, pp. 73-77.
Abstract: Mesker Park Zoo and Botanic Garden, Evansville, Indiana, has a 46-year old female Asian elephant (Elephas maximus) who is left unchained in a stall with a concrete floor at night.  She has daily access to a yard with a substrate of large rock (number 53 limestone) covered with crushed limestone (number 10 with fines) and an area of sand.  We have an aggressive, free-contact regimen to prevent serious foot problems.  The preventive regimen includes interior exhibit and yard maintenance, general husbandry, daily hands-on inspections, twice a day foot scrubs, and weekly pedicures for all four feet.  To make more efficient use of time, pedicures are done with power tools (planer, sander) in addition to the usual hand tools.  If an incipient problem is detected, treatment is aggressive.  Treatment usually consists of medical soaks, topical antimicrobials, and removal of all necrotic tissue.  In this manner we have been able to contain relatively minor problems and prevent major problems from developing.  Therefore, Mesker Park Zoo and Botanic Garden has instituted a free-contact, preventive foot care program for our Asian elephant.  Incorporated into this program are general husbandry practices, inside and outside exhibit maintenance, daily foot inspections, weekly pedicures, and two-way communication between keepers and veterinary staff.  The program is updated as new problems arise and as old treatments cease to work.  This preventive program allows minor programs to be identified and treated early, thus avoiding any major future problems.

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

McLelland, D., Kirkpatrick, J.F., Rose, K., Dixon, R. Studies on encephalomycarditis virus (EMCV) in a zoologic context. AAZV,AAWV,ARAV,NAZWV Joint Conf.  337. 2001.
Ref Type: Conference Proceeding

Seidon, A., 2001. Procedure for nail reconstruction and treatment for an Asian elephant (Elephas maximus). In: Csuti, B., Sargent, E.L., Bechert, U.S. (Eds.), The Elephant's Foot. Iowa State University Press, Iowa State University Press, pp. 89-91.

Sorensen, D., 2001. A History of Elephant Foot Care at the Milwaukee County Zoo. In: Csuti, B., Sargent, E.L., Bechert, U.S. (Eds.), The Elephant's Foot. Iowa State University Press, Ames, Iowa, USA, pp. 65-68.
Abstract: The Milwaukee County Zoo's management of foot care for four female Asian and two female African elephants evolved over the last twenty years.  During this time, we went from virtually no foot care, through a period of extensive foot care, and finally to the moderate amount of foot care we currently perform.  Problems with overgrown nails and cuticles, minor to serious nail and pad necroses, and a recurring open tract in the foot of one of our elephants were treated in a variety of ways.  Methods used included traditional trimming and soaking of the feet, freezing necrotic tissue, minor surgery, and the wearing of a protective boot.  We are currently experimenting with a polymer-based floor covering.  This chapter presents a brief history of elephant foot problems seen at the Milwaukee County Zoo and the treatment of those problems.  Examples are given from foot care for only three of our Asian Elephants.  While these elephants shared many of the foot problems described, each had her own type of problem that is best illustrated by her particular case.  Information was collected principally from medical records and supplemented with information from keepers' daily report sheets and my memory of events.

West, G., 2001. Occurrence and treatment of nail/foot abscesses, nail cracks, and sole abscesses in captive elephants. In: Csuti, B., Sargent, E.L., Bechert, U.S. (Eds.), The Elephant's Foot. Iowa State University Press, Ames, Iowa, USA, pp. 93-97.

Woodle, K., Kepes, T., Doyle, C., 2001. Making a protective boot for an Asian elephant. In: Csuti, B., Sargent, E.L., Bechert, U.S. (Eds.), The Elephant's Foot. Iowa State University Press,  Ames, Iowa, USA, pp. 103-106.

Barber, M.R., Fayrer-Hosken, R.A., 2000. Possible mechanisms of mammalian immunocontraception. J Reprod Immunol 46, 103-124.
Abstract: Ecological and conservation programs in ecosystems around the world have experienced varied success in population management. One of the greatest problems is that human expansion has led to the shrinking of wildlife habitat and, as a result, the overpopulation of many different species has occurred. The pressures exerted by the increased number of animals has caused environmental damage. The humane and practical control of these populations has solicited the scientific community to arrive at a safe, effective, and cost-efficient means of population control. Immunocontraception using zona pellucida antigens, specifically porcine zona pellucida (pZP), has become one of the most promising population control tools in the world today, with notable successes in horses and elephants. A conundrum has risen where pZP, a single vaccine, successfully induces an immunocontraceptive effect in multiple species of mammals. This review describes the most current data pertaining to the mammalian zona pellucida and immunocontraception, and from these studies, we suggest several potential mechanisms of immunocontraception.

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

Fowler, M.E., Steffey, E.P., Galuppo, L., Pascoe, J.R., 2000. Facilitation of Asian elephant (Elephas maximus) standing immobilization and anesthesia with a sling. Journal of Zoo and Wildlife Medicine 31, 118-123.
Abstract: An Asian elephant (Elephas maximus) required general anesthesia for orthopedic foot surgery. The elephant was unable to lie down, so it was placed in a custom-made sling, administered i.m. etorphine hydrochloride in the standing position, and lowered to lateral recumbency. General anesthesia was maintained with isoflurane administered through an endotracheal tube. After surgery, the isoflurane anesthesia was terminated, with immobilization maintained with additional i.v. etorphine. The elephant was lifted to the vertical position, and the immobilizing effects of etorphine were reversed with naltrexone. The suspension system and hoist for the sling were designed specifically for the elephant house.

Hohenhaus, A.E., (Lungka, G., 2000. Transfusion reactions. In: Feldman, B., Zinkl, J.G., Jain, N.C. (Eds.), Schalm's Veterinary Hematology. Lippinicott, Williams & Wilkins, Baltimore,  Maryland, USA, pp. 864-868.

Morrisey, J.K., 2000. Blood transfusions in exotic species. In: Feldman, B., Zinkl, J.G., Jain, N.C. (Eds.), Schalm's Veterinary Hematology. Lippinicott, Williams & Wilkins, Baltimore,  Maryland, USA, pp. 855-860.

Sellon, D.C., 2000. Blood transfusions in large animals. In: Feldman, B., Zinkl, J.G., Jain, N.C. (Eds.), Schalm's Veterinary Hematology. Lippinicott, Williams & Wilkins, Baltimore,  Maryland, USA, pp. 849-854.

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

Wardrop, K.J., 2000. Clinical blood typing and crossmatching. In: Feldman, B., Zinkl, J.G., Jain, N.C. (Eds.), Schalm's Veterinary Hematology. Lippinicott, Williams & Wilkins, Baltimore,  Maryland, USA, pp. 795-798.

 1999. Equine Medicine and Surgery. Mosby, St. Louis MO USA.

Backues, K.A., Hil, M., Palmenberg, C., Miller, C., Soike, K.F., Aguilar, R., 1999. Genetically engineered Mengo virus vaccination of multiple captive wildlife species. Journal of Wildlife Diiseases 35, 384-387.

Duvivier, D.H., Votion, D., Roberts, C.A., Art, T., Lekeux, P., 1999. Inhalation therapy of equine respiratory disorders. Equine Veterinary Education 11, 124-130.

Fayrer-Hosken, R.A., Bertschinger, H.J., Kirkpatrick, J.F., Grobler, D., Lamberski, N., Honneyman, G., Ulrich, T., 1999. Contraceptive potential of the porcine zona pellucida vaccine in the African elephant (Loxodonta africana). Theriogenology 52, 835-846.
Abstract: Immunocontraception has been successful in controlling free-roaming equids; however, what is the potential for the immunocontraceptive control of the African elephant (Loxodonta africana)? The porcine zona pellucida (pZP) glycoproteins share antigenic domains with the African elephant zona pellucida (elZP) glycoproteins, and anti-zona pellucida serum antibodies have been successfully stimulated. To determine the cross-reactivity of the pZP and elZP, immunocytochemistry was evaluated by light and electron microscopy. Specifically, the binding of polyclonal antibodies against total heat-solubilized-porcine zona pellucida to fixed elephant ovary sections was evaluated. The elZP of primary, secondary and tertiary follicles was recognized by the rabbit-anti-pZP serum, but there was no apparent recognition of the primordial follicles. The ability of anti-pZP antibodies to recognize the elZP demonstrates that there is molecular homology between the pZP and elZP glycoproteins. This homology makes the African elephant a candidate for pZP immunocontraception. Three captive elephants were vaccinated with 400 micrograms pZP with a synthetic trehalose dicorynomycolate (S-TDCM) adjuvant. The elephants received 2 boosters of 600 micrograms pZP at 4 wk and 10 m.o. after the primary vaccination. The vaccinated female elephants developed significant (P < 0.05) titers to pZP over prevaccination levels. These levels persisted for 12 to 14 m.o. after the third vaccination. This preliminary evidence shows that the female elephant can develop significant serum antibody levels to pZP. These levels of antibodies are comparable to those required in horses for successful immunocontraception. Thus, porcine zona pellucida immunocontraception might be used to control elephant populations.

Mills, N.J., 1999. The importance of wound lavage. International Veterinary Wound Management Forum 1, 2-4.

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.

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.

Riddle, H.S. Innovative treatment and study of a nail abscess on an Asian elephant. Fourth International Elephant Research Symposium.  50-51. 1999.
Ref Type: Conference Proceeding

Hunter, P., Swanepoel, S.P., Esterhuysen, J.J., Raath, J.P., Bengis, R.G., Van der Lugt, J.J., 1998. The efficacy of an experimental oil-adjuvanted encephalomyocarditis vaccine in elephants, mice and pigs. Vaccine 16, 55-61.
Abstract: An oil-adjuvanted inactivated encephalomyocarditis (EMC) vaccine was developed to protect a wild population of elephants against a natural outbreak of disease. The experimental vaccine was initially tested for efficacy by challenging mice and pigs. Mice showed protection against challenge and pigs developed high antibody levels. Since both vaccinated and control pigs failed to develop clinical disease, apparently due to the low virulence of the strain in this species, protection in pigs could not be evaluated. Three wild elephants and 12 captive elephant calves given the vaccine developed high antibody titres. All of the captive elephants were protected from a challenge 2 months after vaccination, whereas 6 controls (not vaccinated but challenged) developed fatal or sub-clinical myocarditis. This is apparently the first report of an inactivated EMC vaccine inducing high antibody titres in domestic and wild animals. Due to the potency of this vaccine and the acceptability of the oil adjuvant used, it has potential for use in animals in zoological collections as well as in the pig industry.

Kirkpatrick, J.F., Fayrer-Hosken, R., Grobler, D., Raath, C., Bertschinger, H., Turner, J.W., Liu, I.K.M. Immunocontraception of Free-Ranging African Elephants in Kruger National Park, South Africa. 1998 Proceedings AAZV and AAWV Joint Conference.  434-435. 1998. 1998.
Ref Type: Conference Proceeding
Abstract: In order to seek a more publicly acceptable alternative to the management of African elephants by culling, a test was conducted to determine if a porcine zona pellucida (PZP) vaccination could effectively contracept females of this species. Initially, ovaries were recovered from culled animals and slices were incubated with immunogold-labeled rabbit antibodies against PZP. Significant staining of the elephant zona suggested that PZP would be an effective contraceptive vaccine. In a second experiment, three captive female zoo elephants were inoculated with the PZP vaccine (400 ug PZP + 300 mg RIBI). These non-breeding animals were tractable and blood samples were recovered and assayed for anti-PZP antibodies. Antibody titers (1:500 dilution) peaked (0.75 - 1.3 OD) at 1-2 mo following the initial inoculation, declined to 0.1 - 0.34 at 6 mo - 1 yr, and peaked again following a third inoculation (0.8 - 2.3).  These data indicated that African elephants would mount a significant antibody response to the PZP vaccine and together with the histochemical study, suggested the vaccine would be a successful immunocontraceptive in this species.

Molan, P.C., 1998. A brief review of the use of honey as a clinical dressing. Primary Intention (The Australian Journal of Wound Management) 6, 148-158.

Backues, K.A., Aguilar, R.A., Hill, M., Palemberg, A.C. A new modified live virus vaccine for encephalomyocarditis (EMC) virus protection, preliminary trials at the Audubon Zoo. Proc. Amer.Assoc. of Zoo Vet.  166-167. 1997.
Ref Type: Conference Proceeding

Gage, L.J., Blasko, D., Caton, D. The use of direct contact infrared irradiation to aid the healing of pressure sores in elephants (Elephas maximus). Proceedings American Association of Zoo Veterinarians.  187-189. 1997.
Ref Type: Conference Proceeding

Seidel, B., Wunsch, U., Knaus, B.U., Valentin, A., Schroder, H.D. Chemotherapy of chronic, suppurative pododermatitis using an antineoplastic agent in an Asian elephant - a case report. Erkrankungen der Zootiere: Verhandlungsbericht des 38. Internationalen Symposiums uber die Erkrankungen der Zoo- und Wildtiere von 7 bis 11 Mai 1997, in Zurich, Schweiz.  217-220. 1997. Institut fuer Zoo und Wildtierforschung im Forschungsverbund Berlin e.V., Berlin,Germany.
Ref Type: Conference Proceeding

 1996. Principles of validation of diagnostic assays for infectious diseases. Manual of Standards for Diagnostic Tests and Vaccines. Office International des Epizooties (O.I.E.), Paris, pp. 8-15.

Emerson, C.L., Wagner, J.L., 1996. Antibody responses to two encephalomyocarditis virus vaccines in rhesus macaques (Macaca mulatta). J Med Primatol 25, 42-45.
Abstract: Two groups of rhesus macaques (Macaca mulatta) housed in rodent-controlled outdoor corrals were inoculated with two different encephalomyocarditis virus (EMCV) vaccines. One group (n = 45) received a vaccine made from an inactivated field isolate of virus cultured during an outbreak at a zoo in Florida. This vaccine produced fourfold increases in the titers of 28 animals (62%); the increases persisted for at least 18 months (last test) after a single injection of the vaccine. The other group (n = 51) received a vaccine made from an inactivated porcine field strain of the virus. This vaccine did not produce titers in any of the vaccinees.

Kirkpatrick, J.F., Turner, J.W., Jr., Liu, I.K., Fayrer-Hosken, R., 1996. Applications of pig zona pellucida immunocontraception to wildlife fertility
control. J Reprod Fertil Suppl 50, 183-189.
Abstract: A unique application of pig zona pellucida (PZP) immunocontraception is the control of wildlife populations. A native PZP vaccine has been successfully applied to wild horse and donkey populations. A single annual booster inoculation was capable of maintaining contraception. Seven consecutive years of PZP treatment in wild mares resulted in no detectable debilitating side effects, and reversibility of contraception has been documented among mares treated for up to 4 consecutive years. Long-term treatment (5-7 years) is associated with some ovulation failure and depressed urinary oestrogen concentrations. Complex social behaviours in horses were unaffected by treatment. PZP immunocontraception has also been successfully applied to white-tailed deer, with no detectable changes in ovarian histology after 2 years of treatment. Seventy-four species of captive zoo animals have been treated with the PZP vaccine, with documented success in 27 species, including members of the orders
Perissodactyla (Equidae), Artiodactyla (Cervidae, Capridae, Giraffidae, Bovidae), and Carnivora (Ursidae, Mustelidae, Felidae).  Immunocytochemistry studies have demonstrated a high degree of crossreactivity between anti-PZP antibodies and African elephant zona pellucida. The need for a one-inoculation form of the vaccine has led to the incorporation of PZP into lactide-glycolide microspheres, which cause a delayed release of the PZP. PZP immunocontraception of wildlife has potential because of (1) > 90% effectiveness, (2) the ability for remote delivery, via darts, (3) reversibility after short-term use, (4) a wide breadth of effectiveness across many species, (5) a lack of debilitating side-effects even after long-term treatment, and (6) minimal effects upon social behaviours.

Osorio, J.E., Hubbard, G.B., Soike, K.F., Girards, S., van der Werf, S., Moulin, J., Palmenberg, A.C., 1996. Protection of non-murine mammals against encephalomyocarditis virus using a genetically engineered Mengo virus. Vaccine 14, 155-161.

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

Raath, J.P., Bengis, R.G. The evaluation of a vaccine against encephalomyocarditis infection in elephants (Loxodonta africana) under controlled conditions. Proceedings, American Association of Zoo Veterinarians, Wildlife Disease Association, American Association of Wildlife Veterinarians. Joint Conference, East Lansing, Michigan, August 12-17, 1995.  304-308. 1995.
Ref Type: Conference Proceeding
Abstract: Encephalomyocarditis killed 64 elephants in the Kruger National Park between October 1993 and November 1994. An inactivated vaccine was inoculated into 14 elephants aged 6-8 years, 6 of which were challenged later with virulent virus. 3 of 4 infected, unvaccinated elephants developed the clinical disease and 2 died. Vaccinated elephants developed antibodies at 1-4 weeks after vaccination, and the 6 challenged animals remained healthy.

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

Piyadasa, H.D., 1994. Traditional systems for preventing and treating animal diseases in Sri Lanka. Rev Sci Tech 13, 471-486.
Abstract: Systems for preventing and treating animal diseases have been employed in Sri Lanka since ancient times, long before the advent of modern veterinary science. Many such methods have been used, mainly in ruminants but also in trained elephants. Records of animal treatments can be found in historical documents. The first recorded treatment is that of the elephant 'Kadol Etha' belonging to King Dutugemunu (161-137 BC). Later, the physician King Buddhadasa (AD 340-368) is reported to have operated on a snake. The methods and experience gained by practitioners have usually been passed on in secrecy from father to son. However, records on ola leaf manuscripts are available for consultation in the National Museum and the Ayurvedic Research Institute, while others are in the possession of native veterinary practitioners. Approximately 2,000 practitioners are scattered throughout the island; the majority treat animals on a part-time basis. The marking of animals using brands in symbolic shapes, inhalation of medicinal fumes and oral medication are the common treatment methods.

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.

Fowler, M.E., 1993. Foot care in elephants. In: Fowler, M.E. (Ed.), Zoo and Wild Animal Medicine Current Therapy 3. W.B. Saunders Company, Philadelphia, PA, USA, pp. 448-453.

Fowler, M.E., 1993. Zoo and Wild Animal Medicine Current Therapy 3. W.B. Saunders, Philadelphia.

Tripathy, S.B., Das, P.K., 1992. Treatment of Stephanofilarial dermatitis in an Asian elephant (Elephas maximus): a case report. 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. 162-163.
Abstract: Chronic progressive dermatitis to be due to Stephanofilaria in an Asian elephant has been discussed.  The lesions were detected on the toes and heels of both hind feet and on the right abdominal wall. Examination of the skin scrapings and oozing blood over the lesion area revealed presence of microfilarae. Histopathological examination of affected skin revealed hyperkeratosis parakeratosis, acnathosis, granulomatous reactions and perivascular cuffings. Application of 8% metrifonate ointment on Vaseline and Himax base brought clinical cure in 22 and 15 days post treatment, respectively.

Cheng, H.C., Yamashiro, D., 1991. Synthesis and receptor binding activity of elephant beta- endorphin, a beta-endorphin homolog with highly potent analgesic activity. International Journal of Peptide and Protein Research 38, 66-69.
Abstract: Elephant beta-endorphin and its analog, elephant beta- endorphin(6-31) were synthesized by standard solid phase method. Receptor binding activity showed that elephant beta-endorphin was five to six times more potent than human beta-endorphin in its ability to bind to opiate receptors on rat brain membrane. In a previous study (Wong, C.-L., Wai, M.-K., Cheng, H.-C., Chung, D. & Yamashiro, D (1990) Clinical and Experimental Pharmacology and Physiology 16, 33-37), tail flick test for intracerebroventricularly administered beta-endorphin showed that the antinociceptive potency of elephant beta-endorphin was seven to eight times higher than that of human beta-endorphin in mice. Results from both studies suggest that elephant beta-endorphin was a much more potent antinociceptive agent than human beta- endorphin in tail flick test and its higher analgesic activity might be due to its higher affinity for opiate receptors in the brain.

Hoque, M.M., Das, A.K., Wahab, M.a., Rahman, M.L., 1991. Note on the management of traumatic injuries in an elephant. Bangladesh Veterinarian 8, 82-83.

Wallace, C., Woodle, K., Doyle, C., Moore, D., Mofson, E., Walter, B. Making cast metal bands for an Asian elephant's (Elephas maximus) tusks. Proc Am Assoc Zoo Vet. Proceedings American Association of Zoo Veterinarians , 6-8. 1991.
Ref Type: Conference Proceeding
Abstract: Cast silicon bronze metal bands were constructed for an adult bull Asian elephant's tusks to prevent further damage to the tusks and possible pupal injury.  Jeweler's wax was used to make a direct mold of the tusks.  The molds were internally invested in plaster and were externally crafted to meet the desired specifications of the metal bands.  The wax molds were then used directly to make the metal bands in a lost wax casting process.  The metal bands were heated in boiling water, applied to the tusks and cooled for a tight frictional fit.

Myszkowski, J. Bandaging a toe abscess on an Asian elephant (Elephas maximus). Proc Ann Elephant workshop  11.  1990. 
Ref Type: Conference Proceeding

Schanberger, A., Carlson, T., Brown, J., 1990. Successful treatment of chronic toenail cracks in an Asian elephant. Animal Keepers' Forum 17, 243-247.

Swaim, S.F., Henderson, R.A., 1990. Small Animal Wound Management. Lea and Febriger.

Wong, C.L., Wai, M.-K., Cheng, H.-C., Chung, D., Yamashiro, D., 1990. Preliminary study on the antinociceptive effect of elephant beta-endorphin. Clinical and Experimental Pharmacology and Physiology 17, 33-37.
Abstract: 1. Intraventricular administration of human beta-endorphin and elephant beta-endorphin significantly prolonged the tail flick response tested 30 min later. However, elephant beta-endorphin was about 7-8 times more potent than human beta-endorphin in the tail flick test. 2. beta-Endorphin antagonized the antinociceptive effect of both human beta-endorphin and elephant beta-endorphin by the same extent. Naloxone also antagonized the antinociceptive effects of the beta-endorphins but it was less effective than beta-endorphin. 3. Human beta-endorphin and elephant beta-endorphin were of equal potency in inhibiting the abdominal constriction response induced by intraperitoneal (i.p.) acetic acid. Both beta-endorphin and naloxone antagonized these effects of the beta-endorphins with naloxone being more effective. 4. The present study showed that different opioid receptor subtypes may be involved in the tail flick test and the abdominal constriction test. Furthermore, elephant beta-endorphin was a better antinociceptive agent than human beta-endorphin in the tail flick test.

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.

O'Sullivan, T., Easely, M. Elephant hoisting: a necessity in the care of elephants. Proc.Ann.Elephant Workshop 10.  41-42. 1989.
Ref Type: Conference Proceeding

Vogralik, V.G., Vogralik, M.V., 1988. Acupuncture. Avicenum, Praha (Prague).

Gaskin, J.M., Andresen, T.L., Olsen, J.H., Schobert, E.E., Buesse, D., Lynch, J.D., Walsh, M., Citino, S., Murphy, D., 1987. Encephalomyocarditis in zoo animals: Recent experiences with the disease and vaccination. Proceedings of the 1st International Conference on Zoological and Avian Medicine 491.
Abstract: Encephalomyocarditis (EMC), a specific viral infection caused by a group of antigenically related viruses in the family Picornaviridae, a genus of Cardiovirus, continues to be a source of sporadic mortality loss in zoo animals in Florida.  Deaths in a young Nyala antelope, 2 chimpanzees, 3 llamas, a two-toed sloth, 3 ringtail lemurs, a ruffed lemur, and an orangutan have recently been confirmed by virus recovery.  Experimental vaccine trials were initiated in pygmy goats, Barbados sheep, and white mice using B-propiolactone inactivated virus preparations.  Various adjuvants, including aluminum hydroxide, mineral oil, and dimethyl dioctadecyl ammonium bromide (DDAB) were used to enhance the immune responses to inactivated virus.  The vaccine preparations produced varying levels of hemagglutinations-inhibition (HI) antibodies in the immunized animals.  Experimental challenge of unvaccinated weaned pigs, pygmy goats, and Barbados sheep demonstrated that, although they seroconverted, they did not become ill when exposed to the virulent EMC virus strains used in this study. Laboratory mice, however, proved to be very susceptible when exposed to these same strains, and either died acutely or developed posterior paresis and paralysis subsequent to challenge.  All experimental vaccine preparations protected mice against challenge.  In vaccinated goats and sheep, the oil-emulsion-adjuvanted and DDAB-adjuvanted vaccines produced the highest and most persistent HI antibody titers.  Sera obtained from African elephants were screened for HI antibodies to EMC virus.  Ninety-three African elephant sera from the Kruger National Park in the Republic of South Africa had titers of less than 10 hemagglutination-inhibition units (HIU) while 4 of 76 imported juvenile African elephants had titers from 10-40 HIU and the rest had no titer.  EMC virus infections are apparently acquired in Florida from reservoir hosts and HI titers of 40 HIU or higher indicate subclinical infection with the virus.  Experimental vaccines may help prevent EMC in susceptible species; HI responses to vaccination in various exotic species are being evaluated.

Fowler, M.E., 1986. Zoo and Wild Animal Medicine. W.B. Saunders, Philadelphia.

Merkt, H., Ahlers, D., Bader, H., Rath, D., Brandt, H.P., Boer, M., Dittrich, L., 1986. Aftercare and recovery of a female Indian elephant after delivery of a dead fetus by episiotomy. Berl. Munch. Tierarztl. Wochenschr. 99, 329-333.

Wallace, K. Tusk repair of an African elephant. Proc.Ann.Elephant Workshop. 7, 25-28. 1986.
Ref Type: Conference Proceeding

Baxby, D., 1982. The surface antigens of orthopoxviruses detected by cross-neutralization tests on cross-absorbed antisera. J Gen Virol 58 (Pt 2), 251-262.
Abstract: Cross-neutralization tests were done on accepted species and recently isolated members of the genus Orthopoxvirus using antisera which had been separately absorbed with the various viruses. The results provided evidence for the involvement of four neutralizing antigens, and their distribution among 13 virus strains was determined. Monkeypox (Congo-8-Lombe), camelpox (Gorgan), ectromelia  (Mill Hill), 'Lenny' and elephant poxviruses had distinctive antigenic formulae. Lister and Wyeth vaccines were indistinguishable but different from Copenhagen and EM63 vaccines which were themselves distinct. Cowpox (Brighton), buffalopox (BP4), MK 10, and Moscow poxviruses were indistinguishable. Examples were found where viruses shared surface antigens but were not all neutralized by antibody to them. This reduced the practical value of the technique for virus identification. Evidence was also obtained for the existence in some viruses of a fifth antigen, antibody to which could block neutralization by antibody to one particular antigen.

Haight, J., Henneous, R., Groves, D., 1981. Specialized tools for elephant foot care. In: Mellen, J., Littlewood, A. (Eds.), Recent developments in research and husbandry at the Washington Park Zoo. Washington Park Zoo, Portland, Oregon, pp. 71-73.

Read, B. Elephant hoisting procedures at the St. Louis Zoo. AAZPA Regional Conference Proc. AAZPA Regional Conference Proceedings , 326-327. 1981.
Ref Type: Conference Proceeding

Cumbersome cast. Macomb Daily . 1980.
Ref Type: Newspaper

Hobbled but alive. The Detroit News October 23, 4A. 1980.
Ref Type: Newspaper

Swaim, S.F., 1980. Management of contaminated and infected wounds. Surgery of Traumatized Skin. W.B. Saunders, Philadelphia, pp. 119-213.

Obi, T.U., 1978. Traumatic granuloma in an African elephant, Loxodonta africana, and its treatment with yatren-casein. East African Wildlife Journal 16, 69-71.

 1976. Hastividyarnava. Publication Board, Assam, India.

Miller, R.M., 1976. Use of commercially-bottled water in emergency intravenous fluid therapy for large animals. Veterinary Medicine Small Animal Clinician 71, 442-444.

Jainudeen, M.R., Scheurmann, E., 1975. Diseases of the working elephant (Elephas maximus) in Sri Lanka (Ceylon) with special reference to diagnostic and therapeutic possibilities within the
country. Deutsche Tierarztliche Wochenschrift 82, 355-359.

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

Gale, U.T., 1974. Burmese timber elephant. Trade Corporation, Rangoon, Burma.

Siegel, I.M., 1973. Orthotic treatment of tibiotarsal deformity in an elephant. Journal of the American Veterinary Medical Association 163, 544-545.

Gehring, H., Mahnel, H., Mayer, H., 1972. Elephant pox. Zentralbl. Veterinarmed. [B]. 19, 258-261.

Taylor, G.A., 1970. Treating elephants with short-wave diathermy. Physiotherapy 56, 62-64.

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.

Evans, G.H., 1961. Elephants and Their Diseases: A Treatise on Elephants. Government Printing, Rangoon, Burma.

Nicholson, B.D., 1956. The African elephant: How to shoot it humanely, when necessary. African Wild Life 10, 25-36.

Deraniyagala, P.E.P., 1955. Some Extinct Elephants, Their Relatives and the Two Living Species. Ceylon National Museums publication, Government Press, National Museum, Colombo (Sri Lanka).

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

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

Evans, G.H., 1910. Elephants and Their Diseases: A Treatise on Elephants. Government Printing, Rangoon, Burma.

Return to Database Index

Return to Top

.

 HOME   Who We Are   What We Do   What You Can Do  Database   Bulletin Board 
 Vet Formulary   Protocols   Conservation   Image Gallery   Links   Contact Us   Sitemap

Website created, designed, and  copyright © 2002-06 by Hank Hammatt.  Images copyright © 2002-06 by Hank Hammatt - Click here to get information on image use.   All other rights reserved.   Contact Webmaster