This chapter describes (standing) sedation, general anesthesia, intubation and epidural anesthesia using xylazin, ketamine, azaperone, detomidine, medetomidine, etorphin, carfentanil, gas anesthesia and lidocain. To procedures This page describes the following procedures Standing sedation General anesthesia Epidural anesthesia Anesthesia Standing sedation Sedation: In case the elephant does not cooperate voluntarily with the manipulations needed for the diagnosis or treatment the animal should be sedated (including herd mates if needed to reduce stress in the herd) Standing sedation can be performed using xylazine or (preferred) detomidine in combination with butorphanol. Medetomidine works as good as detomidine, but is more expensive. Young elephants need the higher dose range compared to older elephants. Elephants that are excited can be premedicated with azaperone (Asian elephant 0.024-0.038 IM, African elephant 0.056-0.107 IM, IV). Detomidine 0.01-0.022 mg/kg IM (can be reversed by atipamezole at 3-5 times the dose of detomidine). Young calves may need a higher dose of detomidine (0.02-0.04 mg/kg). AND Butorphanol 0.015-0.025 mg/kg given at same time as detomidine. Butorphanol can be reversed with naltrexone at 2.5-5 times the dose of butorphanol in emergency situations, but reversal is not essential and should preferably not be carried out if the calf is considered to be in pain. Alternative option for sedation (if the above mentioned drugs are not available): Xylazine : 0.04-0.08 mg/kg IM for adult Asian elephants and 0.08-0.1 mg/kg for African elephants. Juvenile Asian elephants: 0.09–0.15 xylazine mg/kg IM (Jansson 2021) If insufficient sedation is obtained by xylazine alone, an additional (low) dose of ketamine (0.03 – 0.06 mg/kg) can be given IM or IV. Xylazine can be reversed with yohimbine (0.073-0.098 mg/kg slowly IV) or atipamezole (0.1 x xylazine dose IM or 30/70 IV/IM) Another alternative option for sedation of Asian elephants: Dexmedetomidine : 2 μg/kg BM IM will provide sufficient standing sedation for approximately 70 minutes. (Buranaprim, 2022). Dexmedetomidine can be antagonized by atipamezole (10 times the dexmedetomidine dosage). If a young calf needs to be sedated, it may be necessary to sedate the dam or other adult herd mates so they are not stressed during manipulations on a calf. This can be done by the administration of: Butorphanol 0.006 mg/kg IM and detomidine 0.0026 mg/kg IM (In adult female Asian elephants, 20mg butorphanol and 10mg detomidine have been effective) Sedation can be reversed as described above but is not necessary Alternatively, xylazine (0.04–0.08 mg/kg) or other sedative agents (e.g. Azaperone at 0.024–0.038 mg/kg) can be used if detomidine is unavailable. Laubscher LL et a. 2021 described a fixed drug combination of butorphanol, azaperone and medetomidine (BAM) for African elephants. The dose is given per cm shoulder height. The composition of this anesthetic mixture is: 30 mg/ml butorphanol, 12 mg/ml azaperone, and 12 mg/ml medetomidine. The use of this combination can be recommended in captive, trained African elephants at a dose of 0.006 6 ± 0.001 ml/cm shoulder height. Oral or rectal administration of detomidine in the form of a gel (Domosedan gel, 20-50 mcg/kg) to obtain mild sedation has been described (2020, Molter). The gel must be rubbed into the oral mucosa or rectal wall. Initial, mild sedation is seen after 15-20 minutes. The maximal effect is at 30-45 minutes. A full standard sedation is characterized by the following signs: Salivation Relaxation of the trunk; the tip of the trunk will touch the ground. Relaxation of the penis and (less obvious) relaxation of the vulva. Snooring sounds. It is important to cover the eyes with gauze pads (taped to the skin with Leucoplast or ducttape) and put cotton plugs in the ears. This will deepen the sedation and reduce the risk of sudden wakening. One should always be prepared that the elephant may wake up. Safety procedures need to be discussed in advance with everyone involved in the procedure. Summary agonist - antagonists Xylazine can be reversed by atipamezole : 0.1 x xylazine dose or yohimbine : 0,05-0,13 mg/kg IV Detomidine is reversed by: atipamezole: 3-5 times the detomidine dose IM or slow IV (30/70 IV/IM) Butorphanol is reversed by naltrexone: 2.5-5 x butorphenol dose IV. Skip naltrexone if pain relieve is desirable. The naltrexone dosage provided by Laubscher LL et a. 2020 is much lower: 1 mg naltrexone per mg butorphanol. References: Buranapim, N., Kulnanan, P., Chingpathomkul, K., Angkawanish, T., Chansitthiwet, S., Langkaphin, W., Sombutputorn, P., Monchaivanakit, N., Kasemjai, K., Namwongprom, K., Boonprasert, K., Bansiddhi, P., Thitaram, N., Sharp, P., Pacharinsak, C., Thitaram, C., 2022. Dexmedetomidine Effectively Sedates Asian Elephants (Elephas maximus ). Animals 12, 2787.. doi:10.3390/ani12202787 Fowler M.E. and Mikota S.K. 2006. Chemical restraint and general anesthesia. In: Biology, medicine and surgery of elephants. Blackwell Publishing. Jansson T., Vijitha P.B., Edner A., and Fahlman A. 2021. Standing sedation with xylazine and reversal with yohimbine in juvenile Asian elephants ( Elephas maximus ). Journal of Zoo and Wildlife Medicine, 52(2) : 437-444. Liesel L. Laubscher , Silke Pfitzer , Peter S. Rogers , Lisa L. Wolfe , Michael W. Miller , Aleksandr Semjonov , Jacobus P. Raath. 2021. Evaluating the use of a butorphanol-azaperone-medetomidine fixed-dose combination for standing sedation in African elephants (Loxodonta africana). J. of Zoo and Wildlife Medicine, 52(1) :287-294 (2021). Molter C. 2020. Diagnosis and treatment of EEHV-hemorrhagic disease. Proceedings of the annual AAZV- symposium 2020. Neiffer D.L. , Miller M.A., Weber M., Stetter M., Fontenot D.K., Robbins P.K., and Pye G.W. 2005. Standing sedation in African elephants (Loxodonta africana) using detomidine–butorphanol combinations. Journal of Zoo and Wildlife Medicine 36(2): 250–256, 2005. E. Wiedner. 2015. Proboscidea. In: Fowler's Zoo and Wild animal Medicine 8. Standing sedatin General Anesthesia General remarks: General anesthesia is required in those cases where standing sedation alone or in combination with local anesthesia does not suffice for the intervention that needs to be done. We can devide the indications in: Capture immobilization Immobilization for painful procedures Capture immobilization is mostly done in range countries. However, the escape of a captive elephant may also require capture immobilization. Elephants from this category have not been prepared for the immobilization. This means that they have been able to take food an water shortly prior to the immobilization. It aslo nmeasn that the circumstances have not (or insufficiently) been prepared for the procedure as compared to an immobilization under full captive conditions. Preparation : If possible, prepare a safe area for the people and elephant involved. Avoid an area with water and select a place that is reachable for heavy equipment. Provide shadow whenever possible. Make sure you can ccol the elephant with cold water when necessary. Heavy equipment to position the elephant in lateral recumbancy may be needed, as sternal recumbancy is highly associated with anesthetic death. If an elephant has gone down in sternal position and cannot be rolled over in lateral recumbancy, the anesthesia must be reversed immediately. Whenever possible, provide a soft bedding, preferably a deep sand layer covered by a deep layer of straw or matrasses. Straps or belts are required in case the elephant needs to be rolled over. It is important to thraw them under the elephant before the animal will go down. It helps if the elephant lays on sand and straw to get straps or a belt under the elephant's body with the help of a hooked steel wire. To protect the tusks against fractures, a car tyre can be placed under the head just before the elephant goes down. Trained elephant can be anesthetized when brought lateral recumbency. If the elephant is trained to ly down in sternal position, general anesthesia can be induced but this is very risky! Once the drugs have reached their effect, the elephant MUST be rolled over into lateral recumbency, which requires heavy equipment. Especially in trained elephants, ropes can be used to guide the elephant into lateral recumbency. Trained captive African elephant brought under general anesthesia while guided by ropes. Courtesy: Osterhaus and Fagan. For correct positioning of the elephant during general anesthesia, the use of a crane is highly recommended. First, a standing sedation is induced. After a net has been brought into position, this can be connected to the crane. This will support the elephant when the general anesthesia is induced by IV or IM injection of the narcotic drug (etorphine or ketamine). By lifting the elephant it can be positioned in the correct lateral recumbancy. Protecting cushions, matrasses and soft bedding materials should be placed underneath the head and the body. See the images of the use of a net below (Courtesy basel Zoo): Elephants should be fastened for 24-48 hours prior to anesthesia. Water should be withheld for 24 hours before the procedure. Capture immobilization is mostly done in range countries. The escape of a captive elephant may also require capture immobilization. Elephants from this category have not been prepared for the immobilization. This means that they have been able to take food an water shortly prior to the immobilization. It also means that the circumstances have not or insufficiently been prepared for the procedure as compared to an immobilization under full captive conditions. Preparation: if possible, prepare a safe area for the people and elephant involved. Avoid an area with water and select an area that is reachable for equipment. Provide shadow whenever possible. Make sure you cool the elephant with cold water when necessary. Heavy equipment to position the elephant in lateral recumbancy may be needed, as sternal recumbancy is highly associated with anesthetic death. If an elephant has gone down in sternal position and cannot be rolled over in lateral recumbancy, the anesthesia must be reversed immediately. Whenever possible, provide a soft bedding, preferably sand covered by a deep layer of straw or matrasses. If straps are required in case the elephant needs to be rolled over, it is important to thraw them under the elephant just before the animal will go down. It helps if the elephants lays on sand and straw to get straps or a belt under the elephant's body with the help of a hooked steel wire. The use of a suitable net is highly recommended as slings may slide away from the desired place of the elephant's body. Oxygen supplementation Oxygen must always be provided, even if the anesthetized elephant is not intubated. Arterial blood pressure will drop if no oxygen is provided (Heard 1986). An oxygen flow of 10-15 L/min for a juvenile up to 39-40 L/min for an adult elephant is required for maintaining arterial blood pressure at an acceptable level. Oxygen supply during general anesthesia of a 5 yr-old Asian elephant under field conditions. Due to lack of proper equipment, intubation was not possible. Oxygen was provided at a flow rate of 10 L/min via a small tube inserted in the trunk. Drugs used for general anesthesia: Captive elephants that are excited can be premedicated with azaperone (Asian elephant 0.024-0.038 IM, African elephant 0.056-0.107 IM, IV). Fast acting immobilizing drugs that are used for capture immobilization: Etorphine : 0.002-0.004 mg/kg IM (Asian elephant) and 0.0015-0.003 mg/kg IM (African elephant) OR Carfentanil : 0.002-0.004 mg/kg (Asian elephant) and 0.0013-0.0024 mg/kg IM (African elephant) These drugs can be antagonized with naltrexone 0.004 mg/kg IM (or 50/50 IV/IM) If carfentanil and etorphine are not available, xylazine (0.1 mg/kg) and ketamine (0.3-0.7 mg/kg) can be given together. The disadvantage is the large volume required for an adult elephant. For capture immobilization this combination is therefore not recommended. At the end of the procedure xylazine can be reversed with atipamezole (0.1 x dose of xylazine IM or slowly IV) or yohimbine (0.05-0.13 mg/kg IV). Under controlled conditions (if a crane is available) a standing sedation can be induced first, allowing to put a net or slings in place. When well secured, ketamine can be given i.m. (0.3-0.7 mg/kg). or i.v. using a long infusion tube for safety reasons. Once in lateral recumbancy, the elephant can be intubated and anesthesia can be maintained on isoflurane or halothane (1.5-3%). Inhalation anesthesia and intubation: Intubation in elephants is straightforward. A 30-50 mm diameter cuffed endotracheal tube can be inserted into the trachea. A rope around the lower jaw can be used to open the mouth. A gloved hand can reach the epiglottis and advance a lung tube (e.g. stocha tube for horses) into the trachea, while pushing the soft palate upward. Once in place, the endotracheal tube can be advanced into the trachea guided by the smaller tube. A special portable pressure ventilater has been developed and described by William et al. Jeff Zuba made some modifications to this design, which is now commercially available (http://www.incaseofanesthesia.com/Home_Page.html ). Schematic overview of a portable pressure ventilation device for elephants. "Zuba" ventilator used in an adult African elephant under field conditions Captive African elephant intubated for gas anesthesia using a "Zuba" ventilator. "Zuba" ventilator Under less favorable circumstances when a pressure ventilator is not available, intubation can be done in the trunk using 2 cuffed horse endotracheal tubes and 2 separate (portable) anesthetic machines (Tamas 1983). The advantages of this method are the easy intubation and the ample space in the oral cavity in the absence of the large tube. However the disadvantages are substantial: Two tubes increase the airway resistence Risk of regurgitation and aspiration of stomach contents An elephant can breath through its mouth, which will bypass the inhalation of the anethetic gas General anesthesia in a captive Asian elephant using bilateral trunk intubation (Rotterdam Zoo, 1989) Monitoring: Pulse oximetry is a reliable tool for monitoring heart frequency and venous oxygen saturation. A capnagraph is recommended to monitor the respiration. If not available, one individual should be assigned just to monitor respiratory rate and depth. ECG and arterial blood gases are recommended. As hypotension is quite common in anesthetized elephants, blood pressure measurement is also recommended. Hypotension has been treated successfully with ephedrine and dobutamine. Recovery support: Weak or debilitated animals may need help to get back on their feet during recovery. A deep sand layer is essential for the elephant to getting grip on the ground. A crane may be needed to lift the animal from the ground, using straps or belts applied around the body. References. Fowler M.E. and Mikota S.K. 2006. Chemical restraint and general anesthesia. In: Biology, medicine and surgery of elephants. Blackwell Publishing. Heard D.J., Jacobson E.R., and Brock K.A. 1986. Effects on oxygen supplementation on blood gas values in chemically restraint juvenile African elephants. J Am Vet Med Ass 189 (9)1071-1074. Tamas PM. and Geiser D.R. 1983. Etorphine analgesia supplemented by halothane anesthesia in an adult African elephant. JAVMA 183, 11 (1312-1314) . Wiedner E.. 2015. Proboscidea. In: Fowler's Zoo and Wild animal Medicine 8. Zuba J.R., Osterhaus J.E. 2012. Anesthetic complications and clinical intervention in opiod anesthetized captive elephants. In: Proceedings of the AAZV Conference, Oakland (1-6). Zuba J.R. http://www.incaseofanesthesia.com/Home_Page.html General anesthesia Always bring the elephant into LATERAL RECUMBANCY for general anesthesia Epidural anesthesia Epidural anesthesia in elephants is recommended when a vaginal vestibulotomy is performed in order to reduce tail movements of the elephant and provide additional analgesia in the perineal region. Procedure: Restrain the elephant as appropriate in a chute and sedated if necessary. Disinfect the injection site. Move the tail up and down to determine the position of the most mobile intercoccygeal space. Inject local anaesthetic (2% Lidocaine) into the skin over the injection site. Palpate the intercoccygeal space wearing a sterile glove and insert the needle (14 gauge, 3 inch) at approximately a 60 - 70 degree angle cranially. The epidural space is about 6.5 cm below the skin surface. Inject Lidocaine : 30 ml was sufficient to produce tail relaxation in a 3,000 kg elephant, and the elephant remained standing. Epidural anesthesia

Elephants in captivity can be vaccinated against Rabies, Foot-and mouth disease, Cowpox, Clostridiosis, Pasteurellosis and Anthrax. Vaccination Written by Willem Schaftenaar Introduction Based on historical data on infectious diseases which may have severe clinical impact on elephants kept under human care, vaccination against some of these diseases is recommended. The choice for a certain vaccine depends on the environmental pathogen pressure, the way the elephant is kept (zoo – semi free ranging) and the location/climate. Unfortunately there is not much scientific evidence of the efficacy for some of the vaccines available, as true vaccination challenge trials are not possible in the case of elephants. Data on vaccine induced antibody titers are scarce (Muir, 2021; Lindsay, 2010). In a study about maternal antibody transmission and the lifespan of antibodies, it was found that maternal antibody levels in the elephant calf were as high as in the dam after vaccination of the pregnant dam against tetanus and rabies. These antibodies remained elevated for 144 days (Noffs, 2013). Similar results were found for EEHV-antibodies in naturally infected elephants in which case the antibodies remained elevated until 36 months (Fuery, 2020). Vaccination has been practiced against the following diseases: Tetanus Anthrax Cowpox Clostridium spp. Rabies Pasteurellosis (Hemorrhagic septicemia) Foot-and-mouth disease References Fuery, A, Pursell,T., Tan, J, Peng, R, Burbelo, P.D., Hayward, G.S., Ling, P.D.2020. Lethal Hemorrhagic Disease and Clinical Illness Associatedcwith Elephant Endotheliotropic Herpesvirus 1 Are Caused by Primary Infection: Implications for the Detection of Diagnostic Proteins. J. Vir. Volume 94 Issue 3. Lindsay, W. A., Wiedner, E., Isaza, R., Townsend, H. G., Boleslawski, M., Lunn, D. P. 2010. Immune responses of Asian elephants (Elephas maximus) to commercial tetanus toxoid vaccine. Vet Immunol Immunopathol 133 (2-4), 287-289. Muir, Y.S.S., Bryant, B., Campbell-Ward, M., Higgins, D.P., 2021. Retrospective anti-tetanus antibody responses of zoo-based Asian elephants (Elephas maximus) and rhinoceros (Rhinocerotidae). Developmental & Comparative Immunology 114, 103841. doi:10.1016/j.dci.2020.103841 Nofs S.A., Atmar R.L., Keitel W.A., Hanlon C., Stanton J.J., TanJ., Flanagan J.P., Howard L., Ling P.D., 2013. Prenatal passive transfer of maternal immunity in Asian elephants (Elephas maximus). 2013. Veterinary Immunology and Immunopathology, Volume 153, Issues 3–4, 2013, Pages 308-311. 1. Tetanus (Clostridium tetani ) Only a few cases of clinical tetanus in elephants have been described in the literature (Goss 1947, Burke 1975, Fowler et al 2006) or have been reported anecdotally for Asian elephants in Southeast Asia. In a preliminary study, measurable titers against tetanus were achieved in Asian elephants vaccinated with a 1 ml dose of monovalent equine tetanus toxoid followed by a booster at 4 weeks. The titers remained elevated for >1 year; however, the appropriate vaccination interval has not yet been determined. Annual vaccination is commonly practiced, although it is likely that the duration of immunity may be longer. In a study in which 9 Asian elephants were involved, Muir et al (2021) demonstrated that the antibody titers in these elephants remained at adequate levels with little fluctuations when 3-5 years intervals were applied. Elephants kept in European zoos are recommended to adhere to the suggested vaccination regime for horses with booster vaccinations every 2-3 years. Government owned elephants in Myanmar are routinely vaccinated against tetanus using an equine tetanus toxoid vaccine (5 ml, s.c.); (pers. comm. Khyne U Mar, 2018). The initial course consists of two injections given approximately four to six weeks apart followed by a booster at one year and further boosters annually. References tetanus Goss, L.J. 1942. Tetanus in an elephant. Elephas maximus. Zoologica NY 27:5–6. Burke, T.J. 1975. Probable tetanus in an Asian elephant. JZ&WM, vol 6 – 1 22-24 Mikota, S.K. 2006. Preventive Health Care and Physical Examination. In: Fowler, M.E. and Mikota, S.K.(eds). Biology, Medicine, and Surgery of the Elephant. Blackwell Publishing, Ames, IA. Pp. 67-73. Lindsay, W. A., Wiedner, E., Isaza, R., Townsend, H. G., Boleslawski, M., Lunn, D. P. 2010. Immune responses of Asian elephants (Elephas maximus) to commercial tetanus toxoid vaccine. Vet Immunol Immunopathol 133 (2-4), 287-289 Transmissible Diseases Handbook. 2019. Infectious diseases Fact sheet TETANUS. Muir, Y.S.S., Bryant, B., Campbell-Ward, M., Higgins, D.P., 2021. Retrospective anti-tetanus antibody responses of zoo-based Asian elephants (Elephas maximus) and rhinoceros (Rhinocerotidae). Developmental & Comparative Immunology 114, 103841. doi:10.1016/j.dci.2020.103841 2. Anthrax (Bacillus anthracis ) Outbreaks of Anthrax in livestock are a threat to wildlife, including elephants (Walsh, 2019). Anthrax affects African and Asian elephants, free ranging as well as elephants kept under human care (Lindeque,1994; Yasothai, 2013). The disease can be fatal, however antibodies have been detected in healthy elephants as well (Cizauskas, 2014). Annual vaccination of livestock is the only way to protect wild elephants against this disease. Elephants kept under human care, however, can be vaccinated annually with a commercially available vaccine. This is highly recommended in areas where anthrax is seen in farm animals or if there is a history of anthrax in elephants in that area. An attenuated vaccine (Sterne strain 34F2, https://www.cdc.gov/anthrax/resources/anthrax-sterne-strain.html ) developed for farm animals, has been widely used in government kept elephants in Myanmar under the following recommendations: annual vaccination (1 ml s.c.) in April of elephants older than 6 months, with the exception of sick elephants and pregnant elephants if the fetus is under 8 months (pers. comm. Khyne U Mar, 2018). References Anthrax Lindeque, P.M.; Turnbull, P.C.B.; Verwoerd, Daniel Wynand. 1994. Ecology and epidemiology of anthrax in the Etosha National Park, Namibia. http://hdl.handle.net/2263/33072 Cizauskas ,C.A., S.E. Wendy C. Turner , Vance , R.E., and Getz , W.M. 2014. Frequent and seasonally variable sublethal anthrax infections are accompanied by short-lived immunity in an endemic system. In: Animal Ecology, 83 ( 5 ), 1078-1090 Walsh M.G., Mor S.M., and Hossain S. 2019. The elephant – livestock interface modulates anthrax suitability in India. Proc. R. Soc. B 286: 20190179. http://dx.doi.org/10.1098/rspb.2019.0179 . Yasothai R. 2013. A report on outbreak of anthrax in elephant. International Journal of Science, Environment and Technology, Vol. 2, No 4, 2013, 757 – 759. 3. Cowpox Cowpox (= Orthopox) virus infections have been reported in both Asian and African elephants. Most cases have occurred in Western Europe. Symptoms may vary from minor lesions to fatal infection. Severe cases have been reported more frequently in Asian elephants than in African elephants, but both species are susceptible. The European Association of Zoo and Wildlife Veterinarians (EAZWV)has produced a fact sheet about cowpox infections in zoo animals, including several references to cowpox infections in elephants (Transmissible Diseases Handbook 2019). Prevention: preventive vaccination of African and Asian elephants is strongly recommended by the EAZWV and encouraged in the coordinated European Association of Zoos and Aquaria (EAZA) EAZA breeding programs of both species. The only vaccine available is a Modified Vaccinia Ankara (MVA) vaccine, which is specially produced on request and distributed by the Institut für Infektionsmedizin und Zoonosen, Dr. Robert Fux (Robert.fux@lmu.de ), Veterinärstrasse 13, 80539 München, Germany. MVA has been used for many years in elephants, rhinos and tapirs without any side effects. Primo-vaccination of keepers or other staff members in contact with vaccinated animals is not required. Cowpox vaccination schedule: First vaccination (s.c. or i.m.) of 4 ml MVA at the age of 12-16 weeks. Second vaccination (s.c. or i.m.) of 4 ml MVA 4 weeks after the first injection. The producer of the vaccine advices and offers antibody titer measurement before the vaccination and 3-4 weeks after the second vaccination. In young and untrained elephants this may not be possible, and vaccination should be practiced without titer monitoring. Booster vaccinations: generally once every 2-3 years, depending on the antibody titer. Vaccination during pregnancy: following this vaccination advice, elephants should be immune before they become pregnant. There are no sound studies about the possible side effects of vaccination on the fetus. New non-vaccinated imports or elephants with unknown vaccination status should not be bred before they are properly vaccinated. Remarks: for ordering and using this noncommercial vaccine, a special permit from your official veterinarian is required. Please contact your official veterinarian for further instructions regarding the import of MVA from Germany. Some countries may impose restrictions regarding the contact between humans (staff, visitors) and elephants for the first two weeks after vaccination. However, there is no recommendation for this measure and it is not supported by scientific evidence or by the producer. As MVA only replicates once in mammalian tissues, it is safe and developed for use in humans. References cowpox: Chantrey J, Meyer H, Baxby D, Begon M, Bown KJ, Hazel SM, Jones T, Montgomery WI, Bennett M. 1999. Cowpox: reservoir hosts and geographic range. Epidemiol Infect. 122: 455-460. Eulenberger K, Bernhard A, Nieper H, Hoffman K, Scheller R, Meyer H, Zimmerman P, Essbauer S, Pfeffer M, Kiessling J. 2005. An outbreak of cowpox infection in black rhino (Diceros bicornis) at Leipzig Zoo. Verh ber Erkrg Zootiere. 42:77-85 Kurth A, Nitsche A. 2011. Cowpox in Zoo Animals. In: Miller ER, Fowler ME (eds) Fowler's zoo and wild animal medicine current therapy, Volume 7. Elsevier, St. Louis, Missourri. pp: 32-37. Kurth A, Wibbelt G, Gerber HP, Petschaelis A, Pauli G, Nitsche A. 2008. Rat-to-elephant-to-human transmission of cowpox virus. Emerg Infect Dis. 14: 670-671. Pilaski J, Jacoby F. 1993. Die Kuhpocken-Erkrankungen der Zootiere. Verh ber Erkrg Zootiere. 35: 39-50. Pilaski J, Rosen-Wölff R. 1987. Poxvirus infection in zoo-kept mammals. In: Darai G (ed) Virus diseases in laboratory and captive animals. Martinus Nijhoff Publishing, Boston. pp: 83-100. Pilaski J, Schaller K, Matern B, Klöppel G, Mayer H. 1982. Outbreaks of pox among elephants and rhinoceroses. Verh ber Erkrg Zootiere. 24: 257-265. Pilaski J, Kulka D, Neuschulz N. 1992. outbreak of pox disease in African elephants (Loxodonta africana) at the Thuringer Zoopark Erfurt. Verh ber Erkrg Zootiere. 34: 111-118. Transmissible Diseases Handbook. 2019. Infectious diseases fact sheet: Cowpox virus Wisser J, Pilaski J, Strauss G, Meyer H, Burck G, Truyen U, Rudolph M, Frölich K. 2001. Cowpox virus infection causing stillbirth in an Asian elephant (Elephas maximus). Vet Rec. 149: 244-246. 4. Clostridium spp. Several zoos have vaccinated their elephants against multiple-strain Clostridium spp, with Clostridium perfringens being the major target. Not much is known about the impact of these potential pathogens on the health of elephants. Boonsri et al. describe 2 fatal cases in which C. perfringens was involved (Boonsri, 2018). Both cases were associated with EEHV-infection. A study performed in healthy elephants kept in zoos demonstrated the presence of Clostridium spp . in 3.5% of the Asian elephants (n=85) and no prevalence in African elephants (n=50) (Scharling, 2021). Preliminary data from necropsy reports revealed 13 cases of Clostridium spp involved in the death of Asian elephants (n=226), excluding 5 botulism victims. Of these cases, 5 were attributed to C. perfringens, 1 to C. septicum and 7 were unclassified Clostridium spp. In the same preliminary report, 1 case of C. perfringens involvement was found at necropsy of 112 African elephants (Bacciarini, 2001, Hess A, personal communication 2021). Two cases were identified as C. difficile (Bojesen A.M. 2006). However, it is not clear from most of the necropsy reports whether Clostridium spp. were involved in the primary disease process or just an additional finding. For a long time it was assumed that Clostridium was a fatal pathogen in young elephant, but possibly EEHV-HD cases have been wrongly identified as Clostridium cases. Now that we look more closely at necropsies, the involvement of Clostridium as primary pathogen has become more questionable. Quite severe skin lesions have been anecdotally reported after the use of oil-based vaccines containing multiple Clostridium spp . If the veterinarian decides to use a multiple-strain Clostridium -vaccine, water-based formulations should be used. References Clostridium spp .: Boonsri K., Somgird C., Noinafai P., Pringproa K., Janyamethakul T., T., Brown J.L., Tankaew P, Srivorakul S., Thitaram C. 2018. Elephant endotheliotropic herpesvirus associated with Clostridium perfringens infection in two Asian elephant (Elephas maximus ) calves. Journal of Zoo and Wildlife Medicine 49(1), 178-182. Scharling F.S., Bertelsen M.F., Sós E., Bojesen A.M., 2020. Prevalence of Salmonella species, Clostridium perfringens , and Clostridium difficile in the feces of healthy elephants (Loxodonta species and Elephas maximus) in Europe. Journal of Zoo and Wildlife Medicine 51(4), 752-760. Bacciarini, L. N., Grone, A., Pagan, O., & Frey, J. 2001. Clostridium perfringens 2-toxin in an African elephant (Loxodonta africana) with ulcerative enteritis. Veterinary Record, 149(20), 618–620. doi:10.1136/vr.149.20.618. Bojesen A.M., Olsen K.E.P., Bertelsen M.F. 2006. Fatal enterocolitis in Asian elephants (Elephas maximus ) caused by Clostridium difficile . Veterinary Microbiology , 116 (4), 329-335 5. Rabies For many years, following the recommendation for rabies vaccination in horses has been considered prudent: (inactivated!) vaccine (2 ml IM) given from the age of 6 months, to be repeated after 3-4 weeks and annually boostered. When using this vaccination schedule in elephants, antibodies against rabies could be demonstrated after 24 months (Isaza et al. 2006, Miller et al. 2009). However, this rabies vaccination strategy was evaluated in a herd of 9 African elephants, including two calves, four subadults, and three adults which lead to new conclusions about rabies vaccination strategy. Prior to 2017, elephants were vaccinated opportunistically IM. Starting in 2018, calves at least 4 months of age were administered 2 ml of a commercially available inactivated vaccine and received boosters at 1 y of age. Adults and subadults underwent annual vaccination at the same dose. After 1 year, neutralization titers in five of nine elephants were below levels considered protective in domestic animals (< 0.5 IU/ml). Therefore the dose of rabies vaccine was increased to 4 ml, which resulted in titers more consistently greater than or equal to 0.5 IU/ml for at least 6 months. Institutions with elephants under human care may consider performing rabies vaccination neutralizing titers when possible to help guide vaccination. References: Aravind B., Anilkumar M., Raju S. and Saseendranath M.R. 2006. A case of rabies in an Indian elephant (Elephas maximus). Zoos’ print journal 21(2): 2172. Browning G.R., Peters R., and Howard L.L. 2021. Rabies vaccination and antibody response in African elephants ( Loxodonta africana ) as part of a comprehensive program of veterinary care. Joint AAZV EAZWV Conference Proceedings 2021. Isaza R., Davis R.D., Moore S.M. , and Briggs D.J. 2006. Results of vaccination of Asian elephants (Elephas maximus) with monovalent inactivated rabies vaccine. Am J Vet Res. 2006;67(11):1934-6. Miller, M.A., Olea-Popelka, F., 2009. Serum antibody titers following routine rabies vaccination in African elephants. J. Am. Vet. Med. Assoc 235, 978-981. Wimnalaratne, O., & Kodikara, D. S. 1999. First reported case of elephant rabies in Sri Lanka. Veterinary Record, 144(4), 98–98. http://outbreaknewstoday.com/rabies-kills-elephants-at-kaziranga-national-park-according-to-media-account-anti-rabies-vaccination-drive-underway-36933/ Rabies 6. Pasteurellosis (Hemorrhagic septicemia, Pasteurella multocida ) Hemorrhagic septicemia, caused by Pasteurella multocida (more recently renamed as Mannheimia multocida ) has been reported as a cause of death in elephants (Chandranaik, 2016). 43 out of 85 elephant sera tested positive on antibodies in a newly developed ELISA. As in other mammals, P. multocida is a pathogen that can present on a spectrum from inapparent to a fatal disease. In areas with a pressure of P. multocida in livestock, vaccination of elephants against hemorrhagic disease is recommended. In Myanmar a commercial aluminium-precipitated (inactivated) vaccine has been used for many years in government kept elephants. Elephants older than 6 months are vaccinated twice a year (June and December, 5 ml, s.c.) with the exception of sick elephants and pregnant elephants if the fetus is under 8 months (pers. comm. Khyne U Mar, 2018). References: Chandranaik, B. M., Shivashankar, B. P., Giridhar, P., & Nagaraju, D. N. (2016). Molecular characterisation and serotyping of Pasteurella multocida isolates from Asiatic elephants (Elephas maximus). European Journal of Wildlife Research, 62(6), 681–685. Tankaew P, Singh-La , Titaram C, Punyapornwittaya V, Vongchan P, Sawada T, Sthitmatee N. 2017. Evaluation of an In-house indirect ELISA for detection of antibody against haemorrhagic septicemia in Asian elephants, Journal of Microbiological Methods, Volume 134, 2017, Pages 30-34. https://www.tribuneindia.com/news/nation/elephant-deaths-in-odisha-caused-by-bacteria-central-investigation-team-216885 7. Foot-and-mouth disease (FMD). Very few cases of FMD have been reported in elephants (Rout, 1988; Schaftenaar, 2001) and are always related to outbreaks in livestock. Asian elephants are far more susceptible than African elephants (Schaftenaar, 2001) with a high mortality rate in the Asian species. Outbreaks have been described in India. In most countries vaccination against FMD is strictly regulated by the government in order to conytrol FMD outbreaks in the livestock industry. Whenever elephants are at risk for FMD, government authorities should be contacted and a vaccination program for the animals at risk should be started. The type of vaccine to be used, depends highly on the availability in the country and the FMD-strain that caused the outbreak. Dosages used for cattle should be applied. References: Schaftenaar W. 2001. The occurrence of Foot-and-mouth disease in zoological gardens: a review. Implications of legislation for the present situation in zoos. 2001. Special issue on the 40th international symposium on diseases of zoo- and wild animals. Annual meeting of the EAZWV. 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., 2002, 21 (3), 613-623 Rout M, Nair, N. S. , Biswajit Das , Saravanan Subramaniam , Mohapatra, J. K. , Bramhadev Pattnaik . Foot-and-mouth disease in elephants in Kerala state of India during 2013. Indian Journal of Animal Sciences 2016 Vol.86 No.6 pp.627-631.H. RAHMAN, P. K. DU-ITA and J. N. DEWA. 1988. Foot and Mouth Disease in Elephant (Elephas maximus) J. Vet. Med. B 35, 7C-71 (1988). Transmissible Diseases Handbook. 2019. Infectious disease fact sheet: Foot-and-mouth disease. *Sick elephants and pregnant elephants carrying a fetus is 8 months should not be vaccinated Overview of recommended vaccinations * To page top

Hand-raising Medical Procedures Anesthesia and sedation Basic supplies and equipment Blood collection Blood culture Breast milk collection manually and using a pump Culture collection Enema Fecal analysis Feeding tube placement Fluid therapy - IV / rectal IM injections IV injections IV catheter placement Oxygen therapy Plasma collection and administration – ref EEHV Urine collection (analysis will Vaccinations Wound treatment Postmortem exam Centrifuge, paperfuge, refractometer – simple tests Antibiotics / medications ANESTHESIA AND SEDATION Anesthesia may be required for diagnostic and treatment procedures. The health risks of an anesthetic procedure in young elephants is usually acceptable as long as good procedures are being followed. Most invasive procedures can be done under standing sedation . For larger surgeries, general anesthesia wil be required. BASIC SUPPLIES AND EQUIPMENT Following is a comprehensive list of equipment and supplies that may be needed to carry out the medical procedures that are discussed in this chapter. Larger facilities dedicated to elephant/wildlife rescue and with veterinarians on staff will likely have more of these items on site; small facilities may only need to stock basic items (indicated with a *) and use nearby veterinary clinics or universities for special needs. Equipment Stethoscope Thermometers * ( Click here to see how to measure temperature) Scale * Ophthalmoscope Flashlight/Headlamp* Pulsoximeter Oral speculum Laryngoscope Basic instruments (hemostats, forceps, scissors) Endotracheal tubes and stylets Masks to fit over trunk Oxygen tank and regulator Heat lamps or heated blankets* Chemistry unit (or use local human lab) Hematology unit (or use local human lab) Refractometer Centrifuge Xray machine (preferably digital) The separate clip of this type of pulsoximeter fits on the septum in the trunk tip. A 20 liters tank of medical oxygen can be connected to an oxygen reduction valve. A thin flexible tube can be advanced into the trunk (20-30 cm deep). A permanent flow of 10 liters/minute will increase the oxygen supply to the lungs during general anesthesia

Preventive medicine in elephants include several vaccinations foot care, monitoring for EEHV and tuberculosis and fecal check for parasites Preventive Medicine EEHV Monitoring Fecal check Foot care Tuberculosis γ-interferon testing Tuberculosis DPP tesing Vaccination To page top

The "Infectious diseases"pages directs you to diseases caused by viruses, bacteria, protozoa and parasites. Infectious diseases Virus infections Rabies Foot and Mouth disease Encephalomyocarditis EEHV Pox virus Bacterial infections Tuberculosis Anthrax Salmonellosis Leptospirosis Pasteurellosis Parasite infections Ectoparasites Stomach bots Nematodes Cestodes Trematodes Blood parasites Cutaneous filariasis Zoonotic diseases To page top

A variety of clinical procedures are described here: anesthesia, standing sedation, necropsy, broncho-alveolar lage, trunk wash, body condition score, serum banking, monitoring estrous cycle, pedicure, plasma transfusion, tusk repair, injection technique. Blood collection Hand-rasing Fecal quality control Foot care - curative Foot Care - regular Necropsy procedure Plasma transfusion Surgery Trunk wash procedure Tusk repair procedure Clinical Procedures Anesthesia Banking serum Body condition score Broncho-alveolar & Gastric lavage Injection techniques Monitoring estrous cycle Procedures

The morphology of elephant blood cells is described and demonstrated by photos. To hematology Hematology gallery Compiled by: Willem Schaftenaar and Fieke Molenaar On this page we give examples of normal blood cells stained with Wright-Giemsa. An excellent description of normal and abnormal white blood cells in elephants was published by Stasi et al in 2017. Click here to read that article. Morphology of blood cells, stained with Wright-Giemsa Wright-Giemsa stained blood smear of a healthy adult Asian elephant displaying normal erythrocytes, 1 heterophil, 1 bi-lobed monocyte and several thrombocytes (Courtesy: Rotterdam Zoo). Wright-Giemsa stained blood smear of a healthy adult Asian elephant displaying normal erythrocytes, 1 bi-lobed monocyte, 1 lymphocyte and several thrombocytes (Courtesy: Rotterdam Zoo). The images below were published in the Proceedings of the Zoo and Wildlife Health Conference 2020, 23-31: Molenaar F.M. 2020. Developing haematology skills to enable decision making in suspected cases of Elephant Endotheliotropic Herpesvirus hemorrhagic disease. Heterophil (H), single lobed and bi-lobed monocytes (M), lymphocyte (L). The arrows pont at platelets (Courtesy: Fieke Molenaar). Immature heterophils: bands (Courtesy: Fieke Molenaar). Eosinophil (Courtesy: Fieke Molenaar). Lymphocyte (Courtesy: Fieke Molenaar). Immature lymphocyte (Courtesy: Fieke Molenaar). Monocyte (Courtesy: Fieke Molenaar). Monocytes (Courtesy: Fieke Molenaar). Immature monocytes (Courtesy: Fieke Molenaar). Lymphocyte and 2 monocytes (Courtesy: Fieke Molenaar). Platelets (arrows) (Courtesy: Fieke Molenaar). Erythrocytes: "codocytes" (target cells with a bulls-eye appearance) occur naturally in elephants (Courtesy: Fieke Molenaar). Fragmented erythrocytes Fragments of erythrocytes (schistocytes) as can be seen in elephants suffering of Disseminated Intravascular Coagulation (e.g. EEHV-HD) (Courtesy: Fieke Molenaar). To page top

Clostridiosis in elephants: The following manifestations of clostridiosis have been described in elephants: Tetanus (C. tetani) Enterotoxemia (C. perfringens) Enterocolitis (C. difficile) Malignant edema (C. septicum) Blackleg  (C. chauvoei, C. septicum) Botulism (C. botulinum) CLOSTRIDIOSIS General information Clostridiosis represents a group of diseases caused by members of the Clostridium species. They occur worldwide and can affect many mammalian species, including elephants. Clostridium spp. are gram-positive, rod-shaped, anaerobic bacilli. They form spores that may persist in the soil for months or years. Some of these organisms may be found in the normal flora of the digestive tract and become pathogenic only if accessible tissue is damaged as a result of deep penetrating trauma to the muscle bundles or a compromised gastrointestinal mucosa. Clostridial organisms produce exotoxins, with local and/or systemic effect; including hemolysis and local tissue necrosis. These toxins are produced when the organism grows in the host tissues with the exception of the toxin of Clostridium botulinum , which is formed outside the body and ingested orally by the host. Some Clostridial organisms can produce multiple toxins, each with a specific activity. Clostridiosis in elephants The following manifestations of clostridiosis have been described in elephants: Tetanus (C. tetani) Enterotoxemia (C. perfringens) Enterocolitis (C. difficile) Malignant edema (C. septicum) Clostridium novyi Blackleg (C. chauvoei, C. septicum) has been reported once, but this report could not be tracked down (Prescott, C.W. 1971. Blackleg in an elephant. Vet Rec 88:1971) Botulism (C. botulinum ) Elephant care manual for mahouts and camp managers Preecha Phuangkum Richard C. Lair and Taweepoke Angkawanith Tetanus Tetanus is caused by a long-living anaerobic bacterium that is found in the soil and in moist areas. Tetanus is usually found in elephants that have suffered deep wounds, usually in the foot and particularly through the footpad being pierced by a metal object such as an old, rusty nail. After the bacteria have entered the elephant's body they thrive and, after an incubation period of 15-20 days, neurotoxins are produced that damage the nervous system and cause typical muscular spasms. Between about 1977 and 1992 Thailand experienced, on a massive scale, thieves cutting off elephants' tusks by stealth in order to sell them. One result was that many tuskers contracted tetanus and died. Path of infection: Infection proceeds from stepping on a piece of metal or other contaminated object that causes a deep wound. With elephants, however, the wound might not be obvious because elephants can and do use their trunks to gather dirt (which might be contaminated) to stuff in wounds, including cut tusks. When tetanus enters a tusk's pulp cavity, it spreads very quickly because it thrives in environments where there is no oxygen. All wounds must, of course, be carefully cleaned but be especially careful where the puncture is from nails or rusty old metal, especially in an area that has long housed many animals. After infection, the disease does not progress quickly and the elephant will appear normal for 15-20 days (sometimes even longer) before symptoms appear. Even if the elephant receives treatment, the survival rate is very low. Clinical signs: The elephant often has a temperature of over 37.8° C or 100° F, although this is not certain. The breath will be noticeably hot to feel. The eyes will be very red, and the soft tissue inside the mouth and the trunk will be a dark red. The elephant is listless and does not eat or drink water. The nervous system is affected, and the leg muscles harden in muscular contraction; the tail has a supple, snake-like feel. There are periodic spasms, particularly when the elephant is startled, as by a loud noise or bright light. In following days, it becomes difficult for the elephant to walk and stand because of the contraction of the leg muscles. The jaws lock tightly, making it difficult to chew food. Eating and drinking become very difficult and the elephant dies. Treatment: Consult a veterinarian immediately. Even though tetanus is not contagious to other elephants, separate the elephant from other animals as it will be more peaceful. Take the elephant to a shady shelter with a clean surface, such as a concrete floor (it should not be slippery) to prevent it from introducing earth or other unclean materials into the wound or the pulp cavity. The area should have good ventilation. In cases of an exposed pulp cavity, it is best to clean it with running tap water through a hose. Wash all wounds thoroughly with clean water then flush with an antiseptic solution such as Betadine or Povidine-iodine 1% in a 20:1 solution. Finally, apply an anti-insect powder that includes an antibiotic, such as Negasunt. Hand feed the elephant with small amounts of easy to eat foods with high nutritional value, such as ripe bananas, sticky rice, ripe papayas, etc. Clean the wound every day. Prevention: For elephants that have open wounds or exposed pulp cavities in tusks, prevent the elephant from contracting tetanus by daily cleaning of the wound and by keeping the elephant on a clean surface. Otherwise the elephant is likely to introduce dirt or other unclean material that could contain tetanus germs into the wound. No vaccine yet exists for elephants but if an elephant with a wound seems to have been exposed to tetanus, a veterinarian can inject an antitoxin to prevent infection from the bacteria. To page top Tetanus Tetanus is a potentially fatal disease characterized by muscular spasms caused by a neurotoxin produced by the bacterium Clostridium tetani (vetmed.ucdavis.edu, 2021). These organisms, and their spores, are found in the intestinal tract of several mammalian species and are abundant in the soil, where they can survive for many years. The spores can enter open wounds, particularly puncture wounds, where they proliferate under the right anaerobic conditions. When the spores die, they release the tetanospasmin neurotoxin that is responsible for clinical signs. The size of the wound does not correlate to risk of developing tetanus. Even superficial wounds have been associated with clinical cases. Clinical signs of tetanus in horses usually include history of a wound (typically within the preceding month) and stiffness, lameness, or colic. These signs generally progress quickly to an abnormal gait, trembling, and muscle spasm. An inability to open the mouth, known as “lockjaw”, may occur. Horses can exhibit profuse sweating, saliva accumulation in the mouth, and may aspirate feed material. Excitement, including loud sounds or bright light, often exacerbates clinical signs. Horses may become very sensitive to touch. Stiffness in the leg muscles may result in a characteristic “sawhorse” stance. Affected horses can progress to severe muscle rigidity, making it difficult to rise, urinate, or defecate. Respiratory failure can occur. Tetanus in elephants Only a few cases of clinical tetanus in elephants have been described in the literature (Goss 1947, Burke 1975, Fowler & Mikota 2006) or have been reported anecdotally for Asian elephants in Southeast Asia. Inspection of the pads and nails is imporatant for the detection of wounds. Sharp objects, like steel nails may have penetrated the pad. (Illegaly) cut off tusks may provide an opportunity for C. tetani to infect the tusk pulpa. After an incubation period of 7-20 days, the elephant will show symptoms similar to those seen in horses. Spasms are usually aggravated when the elephant is startled. Burke reports an 8-year-old female that was unable to open her mouth: "She was hypersensitive to noise and touch, becoming tense and raising her tail. Her body temperature was 37°C (98.6°F, normal range 36–37°C /97–99°F). An elevated body temperature can be expected when there are spasms. Although there were several cracks around the toenails, none of the wounds were thought to be anaerobic. 100,000 units of tetanus antitoxin (TAT) were administered and the next day she seemed somewhat relaxed. However, on the third day she was found in lateral recumbency and in tetanic spasms. A sedative (112 grams of chloral hydrate per rectum) was administered. Periodic sedation was necessary to keep her relaxed. She was raised to her feet with a sling and left in the sling overnight. On the fifth day she was unable to stand without the sling. Over the previous 5 days 360,000 units of TAT were administered subcutaneously. The elephant was kept in a sling and force-fed a slurry of bran mash through a stomach tube for 29 days, at which time she began to masticate and swallow feed"(Fowler & Mikota 2006). Treatment Tetanus antitoxin should be administered at a dose of 225 units/kg body weight, half intravenously, the other half intramuscularly. Anaphylactic shock is a hazard of this therapy because tetanus antitoxin is a horse serum product. Be prepared to administer epinephrine Broad-spectrum antibiotics should be administered to kill organisms that may not be reached with wound cleansing. The elephant should be placed in a non-stimulating environment and tranquilized as appropriate. Serum transfusion with serum from a vaccinated elephant should be considered (after cross-matching). Supportive care is crucial to success. Be prepared to sling the elephant. Water may be administered by rectal lavage. For food, the author uses a slurry of quick-cooking rolled oats. The quantity of the breakfast cereal selected is put into boiling hot water, allowed to cool, and then diluted to a consistency that may be pumped through a stomach pump. (Fowler & Mikota 2006). Vaccination In a preliminary study, measurable titers against tetanus were achieved in Asian elephants vaccinated with a 1 ml dose of monovalent equine tetanus toxoid followed by a booster at 4 weeks. The titers remained elevated for >1 year; however, the appropriate vaccination interval has not yet been determined. Annual vaccination is commonly practiced, although it is likely that the duration of immunity may be longer. In a study in which 9 Asian elephants were involved, Muir et al (2021) demonstrated that the antibody titers in these elephants remained at adequate levels with little fluctuations when 3-5 years intervals were applied. It is therefore recommended to adhere to the suggested vaccination regime for horses with booster vaccinations every 2-3 years. References tetanus Goss, L.J. 1942. Tetanus in an elephant. Elephas maximus. Zoologica NY 27:5–6. Burke, T.J. 1975. Probable tetanus in an Asian elephant. JZ&WM, vol 6 – 1 22-24 Fowler, M.E. and Mikota, S.K. 2006. Preventive health care and physical examination / Chemical Restraint and General Anesthesia in. In: Biology, Medicine, and Surgery of Elephants. 2006. Ed. Fowler & Mikota page 68-84, 147-148. Lindsay, W. A., Wiedner, E., Isaza, R., Townsend, H. G., Boleslawski, M., Lunn, D. P. 2010. Immune responses of Asian elephants (Elephas maximus) to commercial tetanus toxoid vaccine. Vet Immunol Immunopathol 133 (2-4), 287-289 Transmissible Diseases Handbook. 2019. Infectious diseases Fact sheet TETANUS (Annex 4) Muir, Y.S.S., Bryant, B., Campbell-Ward, M., Higgins, D.P., 2021. Retrospective anti-tetanus antibody responses of zoo-based Asian elephants (Elephas maximus) and rhinoceros (Rhinocerotidae). Developmental & Comparative Immunology 114, 103841.. doi:10.1016/j.dci.2020.103841 https://ceh.vetmed.ucdavis.edu/health-topics/tetanus Tetanus Enterotoxemia (C. perfringens) Enterotoxemia is caused by the toxin of Clostridium perfringens . There are 4 subtypes of C. perfringens, all grwoing under anaerobic conditions that have been associated with elephants: type A, C, D and E. The diagnosis 'enterotoxemia' in based on culture and PCR of the toxin-associated genes in the histological lesions. Clinical manifestation in elephants Although there are few reports of enterotoxemia caused by C. perfringens in elephants , it might be an underreported disease in this species (see references below). Usually the disease has an acute course, with symptoms like diarrhea, colic, lethargy, anorexia and finally collaps in lateral recumbancy. If not treated agressively in time, the elephant usually dies. C. perfringens is an environmental bacterium which can be present in the elephant's gut without doing any harm. Under certain conditions (gastric pH decrease by nutritional overload of easily digestable carbohydrates or badly fermented silage products) it can overgrow the natural gut flora and produce large amounts of toxins that lead to the symtoms described above. Septicemia can lead to multiple abdominal organs involvement, as well as muscles. When young elephants are affected, the disease resembles Elephant Endotheliotropic Herpes Virus-Hemorrhagic Disease ( EEHV-HD ) as the symptoms in both diseases are associated with Disseminated Intravascular Coagulopathy (DIC). In some reports C.perfringens enterotoxemia and EEHV-HD were simultaneously diagnosed in diseased elephants (Boonsri et al. 2018, Costa et al, 2022). The prevalence of C. perfringens in European zoos was studied in 2020: in fecal samples of 86 healthy Asian elephants the presence of type A and type E was PCR-confirmed in 3 animals (2.2%). All fecal samples obtained from 50 African elephants were negative. In an overview of necropsy reports of 226 Asian elephants and 110 African elephants kept in the European Taxon Advisory Group between 1985 and 2018, 4 Asian elephants and 1 African elephant were reported to have died from an ulcerative enteritis caused by C. perfringens (Hes 2022). Few reports on enterotoxima in elephants are available in the literature. One author described the outbreak of C. perfringens in a group of African elephants kept in a European zoo (Göltenboth et al 1974): 2 days after feeding fresh grass, a young elephant developed diarrhea and was lying down more frequently. It was treated with a spasmolytic and vitamin C. The following morning it seemed much better and was returned to the group of 4 young elephants, where it deteriorated within 1 hour and died. At necropsy, severe blood staint edema and gas accumaltion was found in the subcutis of the neck, pharynx and larynx as well as a severe cathharal enteritis and gas accumulation in all internal organs, from which C. perfringens was cultured. A second case in a young elephant of the same herd occured 5 weeks later, again 2 days after feeding fresh grass. Symptoms were even more pronounced and C. perfringens was cultured form all organs (septicemia). The third elephant of the group fell ill a few days later. This animal did not develop diarrhea, but was lethargic and refused to eat and drink for 5 days. Despite of treatment with antibiotics and all kinds of supportive medications (including IV-administration of Clostridium antitoxin), it died after 10 days of illness. At necropsy more chronic lesions were found: enteritis, fatty liver degeneration, bronchopneumonia and myocardial degeneration. In this animal C. perfringens could not be detected. In one fatal case, acute myonecrosis was found in an 8 yr-old Asian elephant, resembling blackleg/ black quarter(C. chovoei) or malignant edema (C. septicum) (Rahman, 2009) . The elephant calf showed clinical signs of sudden illness characterised by loss of appetite with high fever (39°C) and reluctance to walk. The animal was treated with an intramuscular injection of enrofloxacin, 5 mg/kg body weight. The animal did not respond to treatment and its condition deteriorated rapidly. The animal stopped taking feed and water, became recumbent and finally died within 48 h of the onset of clinical signs. At necropsy, dark, discoloured, swollen muscles with rancid odour from the affected region and intramuscular aspirates were observed. C. perfringens was cultured from these lesions and the presence of alpha-toxin genes could be demonstrated by PCR. One case reports describes a fatal infection of Clostridium perfringens type C in an adult Asian zoo elephant (Costa et al. 2022). Evidence of involvement of EEHV4 was demonstrated by qPCR and the presence of intranuclear inclusion bodies in the endothelial cells of the intestinal blood vessels. Treatment of C. perfringens enterotoxemia In most cases it will be hard to make the diagnose in the living elephant. When enterotoxemia is suspected, agressive antimicrobial therapy, preferably based on an antibiogram and supportive therapy is mandatory. Depending on their bioavailability, antibiotics should be given IV or IM. Oral administration might result in low absorption from the intestines due to the enteritis. IV and rectal administration of fluids and IM NSAIDs are highly recommended. Early treatment of enterotoxemia is essential for the survival of the elephant. The list of recommended drugs is shown below. The clinician should not hesitate to administer all these drugs and should even sedate the sick elephant if needed for its treatment. Circulatory support: Rectal fluids: Luke-warm water 10-20 ml/kg BW TID or QID, up to every 2 hours Crystalloids: I V as a bolus of 0.3-4 ml/kg BW Antibiotic treatment: Penicillins are the first choice antibiotics. Penicillin G can be given IV and will have a quick action. Amoxicilline is a good representative as well ( 11 mg/kg IM q 24 h). Pain management: Pain management (opioids, NSAIDs) is recommended if there are clear signs of pain or discomfort: Butorphanol: 0.008-0.014 mg/kg IM Q 4 hrs Flunixin: 0.25 to 0.5 mg/kg IM SID Omiprazole: 0.7 to 1.4 mg/kg PO SID Anti-inflammatory treatment: Gluco-corticosteroid drugs are indicated in case of suspicion of DIC. Dexamethasone: 0.05-0.1 mg/kg IV or IM SID for 1-3 days. Prevention Although there is no scientific data on the efficacy of preventive vaccination, several zoos do practice annual vaccination with a multivalent vaccine. Care should be taken not to use an oil-based adjuvant, as these may cause necrosis around the injection site . As a general precaution, major diet changes should always be introduced slowly. When large amounts of easily digestible carbohydrates (like fresh grass, large amount of vegetables and silage) become available as a major food component, the diet change should be made over period of 7-10 days in order to allow the intestinal flora to adapt to the new diet. References: Bacciarini, L.N., Pagan, O., Frey, J., Grone, A., 2001. Clostridium perfringens b2-toxin in an African elephant (Loxodonta africana) with ulcerative enteritis. Vet. Rec. 149, 618–620. Boonsri, K., Somgird, C., Noinafai, P.,Pringproa, K., Janyamethakul, T., Angkawanish, T., Brown, J.L., Tankaew, P., Srivorakul, S., and Thitaram, C. 2018. Elephant Endotheliotropic herpes Virus associated with Clostridium perfringens infection in two Asian elephants (Elephas maximus) calves. Journal of Zoo and Wildlife Medicine 49(1): 178–182, 2018. Costa T, Rocchigiani G, Zendri F, Drake G, Lopez J, Chantrey J and Ricci E. 2022. Elephant Endotheliotropic Herpesvirus 4 and Clostridium perfringens Type C fatal Co-infection in an adult Asian Elephant (Elephas maximus). Animals 2022, 12, 349. https://doi.org/10.3390/ani12030349. Das A, Mazumder Y, Dutta B.K., Shome B.R., Bujarbaruah K.M. and Sharma G.D. 2008. Clostridium perfringens type A beta2 toxin in elephant (Elephas maximus indicus ) and pygmy hog (Sus salvanius ) with haemorrhagic enteritis in Assam, India. Afr. J. of Microb. Res. Vol.(2) pp. 196-201 2008. Goltenboth, R. and Klos, H.-G. 1974. On several diseases and causes of death in elephants in the Berlin Zoo (Zu einigen erkrankungen und todesfallen bei elefanten des Zoologischen Gartens Berlin. XVI Verhandlungsbericht Internationalen Symposiums Erkrankungen Zoo und Wildtiere, Berlin, Akademie Verlag, pp. 175–179. Hes. A 2022.Thesis: Lesions found in the post-mortem reports of the Asian (Elephas maximus) and African (Loxodonta africana) elephants of the European Association of Zoos and Aquaria. University of Veterinary Medicine BudapestBudapest, 2022. Rahman H., Chakraborty A., Rahman T., Sharma R., Shome B.R. and Shakuntala I. 2009. Clostridial myonecrosis clinically resembling black quarter in an Indian elephant ( Elephas maximus ) Rev. sci. tech. Off. int. Epiz., 2009, 28 (3), 1069-1075, 2009. To page top Enterotoxemia Clostridioides difficile (previous name: Clostridium difficile ) Another potential pathogenic Clostridioides sp . is C. difficile . Clostridia are commonly encountered in the intestinal tract without being associated with disease, as soil and feedstuffs seem to be natural habitats for these organisms. However at rare occasions C.difficile can cause a severe, fatal enterocolitis. As in entertoxemia, the disease can have a fast fatal outcome within 2-3 days. A more chronic course of enteritis was associated with the same strain of C.difficile that had killed 2 adult Asian elephants in the same herd a few days before. This elephant recovered over a period of 5 weeks of severe illness with diarrhea. It was speculated that the feeding of large quantities of broccoli, a rich source of sulforaphane, which has been shown to inhibit the growth of many intestinal microorganisms might have triggered a subsequent overgrowth by C. difficile (Bojesen et al. 2006). The diagnose of C.difficile associated disease is based on aerobic and anaerobic culture and PCR, including the demonstration of toxins. Special culture media have been developed to grow C. difficile . Treatment Metronidazole and vancomycin are used to address clinical disease caused by C.difficile . The sensitivity to these drugs was studied in 6 isolates of C.difficili obtained from feces of clinically healthy Asian elephants (Sthitmatee et al. 2013). There was no evidence of resistance of these isolates to metronidazole and vancomycin. However, sensitivity may vary per country, depending on the antimicrobial policy followed. References Bojesen A.M., Olsen K.E.P. and Bertelsen M.F. 2006. Fatal enterocolitis in Asian elephants (Elephas maximus) caused by Clostridium difficile . Veterinary Microbiology 116 (329–335), 2006. Sthitmatee N., Warinrak T. and Wongkalasin W. 2013. Susceptibility of Clostridium difficile Isolated from Healthy Captive Asian Elephants to Metronidazole and Vancomycin. Thai J Vet Med. 43(2): 313-316. To page top Clostridium difficile Malignant edema Malignant edema (Clostridium septicum ) There is one report on malignant edema in an adult Asian elephant that lived in a European zoo (Goltenboth et al, 1974). The elephant died within 48 hours after the onset of the symptoms, that consisted of lethargy and general malaise. Severe edema was found in the entire intestinal tract. Clostridium novyi Report by Dr. Arun Zachariah et al. (Kerala Forests and Wildlife Department, Kerala, India) 19th International Elephant Conservation and Research Symposium, 2023 Chiangmai - International Elephant Foundation Since 2014, unusual mortality was observed in Asian elephants in Kerala state of South India.26 per acute mortalities were observed in a wild elephant population within a span of two years. Whereas two captive elephants were found dead with similar lesions but sporadic in nature. These animal deaths were per acute with quick autolytic changes and discharge of serosanguineous fluids from external orifices mainly anus. Possibility for Anthrax was ruled. Detailed autopsies were conducted in all the animals. Gross pathological lesions were identified as, petechial to echymotic hemorrhages in major organs, liver was friable with accumulation of gas in the parenchyma, blackening of the sub-cutaneous muscles and accumulation of serosanguineous fluid in the abdominal and pericardial cavity. Gram-positive spore bearing bacteria were seen in blood smear examination. Histologically, there was coagulative necrosis surrounded by inflammatory cells and large numbers of gram-positive rods were observed. High throughput sequencing of conserved 16S ribosomal gene revealed abundance of C.novyi in various tissue samples. Further, liver samples tested by PCR were positive for C. novyi type B flagellin and alpha toxin genes, but negative for other pathologic clostridia. Clostridium novyi type B causes infectious necrotic hepatitis in sheep and less frequently in other species. However reports of C.novyi infections in wild animals were scanty except for few species like Bighorn sheep and farmed Reindeer but not in outbreak proportions. This is the first report of C. novyi infection and mortality in Asian elephants in a large scale. Clostridium novyi Black leg Black leg (Clostridium chauvoei, C. septicum ) There is one report of black leg in a 50 yr-old Asian elephant kept in Australia (Prescott, 1971). The animal was on a diet of fresh grass (grazing), eucalyptus and lucerne hay. Two days before it died, the elephant had been off food and fell against a round timber pallisade, hurting its right shoulder. The following day it was depressed and fell down again and was unable to stand up. It died 52 hours after the first signs of illness. At necropsy the right foreleg was swollen from carpus to shoulder. On incision of the swollen muscles, sero-sanguineous fluid and gas bubbled from the emphysematous tissues. Clostridium septicum was cultured from this fluid. The wall of the stomach and large parts of the intestines was thickened, edematous and inflamed, while the spleen was very distended. References 1. Goltenboth, R. and Klos, H.-G. 1974. On several diseases and causes of death in elephants in the Berlin Zoo (Zu einigen erkrankungen und todesfallen bei elefanten des Zoologischen Gartens Berlin. XVI Verhandlungsbericht Internationalen Symposiums Erkrankungen Zoo und Wildtiere, Berlin, Akademie Verlag, pp. 175–179. 2. Prescott C.W> 1971. Black leg in an elephant. Veterinary Record 83, pp 598-599. To page top To page top Botulism Botulism is caused by the toxin of Clostridium botulinum (FAO). Clostridial organisms are strict anaerobes, meaning they do not grow in the presence of oxygen or in healthy, well-oxygenated tissues. Clostridium botulinum produces seven different neurotoxins, each of which is distinct and different enough from the others that antibodies against one type do not protect an animal against botulism from another type. Botulinum toxin is one of the most potent biotoxins known. Sometimes the onset of Clostridial disease is so rapid that no clinical signs are ever manifested; animals are simply found dead. The toxin is formed by the organisms outside the elephant under certain circumstances, characterized by an anaerobic environment (pH ± 4) and an environmental temperature between 10 and 50°C (FAO). Examples of these sources are poor-quality silage or poor-quality drinking water (anaerobic conditions in a pond without streaming water). Botulism in elephants Botulism was first reported in Asian elephants in a German zoo (Elze 1962). One adult elephant became paralyzed and died within one day. A cause of this sudden death could not be determined. Four days later an adult herd mate started to show the first signs of paralysis. Initially the animal remained standing with the neck stretched in forward direction, mouth opened, salivating and teeth grinding. The elephant only ate some fruits and was extremely weak in all its legs and the trunk. Pulse frequency was 68/minute. The animal went down sleeping several times, but with great strength it managed to get up by itself. On the second day a Botulism-antitoxin serum (Sachsisches Serumwerken A.G. Dresden, DDR) is administered (3x50 ml s.c.). On the next the animal is given 37 x 50 ml of this antitoxin serum, partly s.c., partly intramuscular in 50-100 ml portions in a time span of 2.5 hours. The total dose given was 20-40 times the dose given to humans. No adverse reactions were observed. During the first 8 hours after the administration of the antitoxin, the elephant went down and was almost unresponsive, until it managed to stand up again with the help of human manpower. In the following hours it started eating some fruits and hay. In the following week the animal recovered completely. The diagnosis ‘Botulism’ was made based on the symptoms and the positive reaction on the administration of the Botulism antitoxine. Other drugs that were given throughout the disease episode were caffeine, metamizole, calciumgluconate, Methiovert® (?), Algopyrin®, papaverine and streptomysine-penicilline. A second case of botulism in elephants was reported by Gart et.al (1977). Unfortunately, no details of that report could be retrieved. In 2017 a severe outbreak was reported in a captive bachelor herd of 6 Asian elephant bulls in Spain, which resulted in the death of 5 of the elephants. For the case report “Botulism in elephants”, click here . Botulism has been reported in horses that were exposed to botulism toxin in the feed, usually involving type B and C toxin. Toxin might be present as a contaminant in feed, or if there are droppings or carcasses of small rodents in the feed bunk or water tub. One problem occurs when rodents or other animals die in a field of forage, and a carcass is incorporated into a bale during baling. Contaminated hay cubes have been responsible for at least one large outbreak of botulism in horses. Even if a carcass has undergone dessication (it’s dried out) or is unrecognizable in a flake of hay, enough spores can remain to kill a horse. Toxico-infectious botulism is the second most common form of botulism in horses, and this arises when the bacterium itself is ingested from soil and colonizes the gastrointestinal tract. As it grows inside the body, it produces the toxin, and signs of disease become apparent as toxin is absorbed into the bloodstream from the intestinal tract. Clostridium botulinum type B has been associated with this form of botulism. Symptoms of botulism in elephants The typical symptoms include flaccid muscle paralysis. The major clinical signs consisted of gradually increasing general weakness, shivering, muscle fasciculations (involuntary contractions) or trembling and shaking, particularly in the shoulder and flank muscles, mild to heavy salivation, inability to swallow and stand and properly use the trunk and dilated pupils that respond poorly on light. Death can occur within a few days as a result of respiratory distress. Click here to see for a full description of the histological lesions in the case report described here . Treatment, diagnosis and prevention Treatment of botulism is very challenging: when treatment is started in the early phase of the disease, the administration of specific antitoxins might be helpful, as suggested in the 1962 case. In horses respiratory support is important, however challenging in elephants. Soft bedding should be provided. Eye protection with an eye ointment is important when the elephant has gone into lateral recumbency. During the phase of complete paralysis, the administration of oxygen through the trunk will probably support the oxygen exchange in the elephant’s lungs. A definitive diagnosis of botulism can only be made by performing a mouse bioassay test. Prevention: there is no commercially available vaccine against botulism, except for type B (AAEP) References Andrés Gamazo PJ, Pavón E, Stumpel J, Bouts T, Schaftenaar W, Kik M, de los Ángeles Jiménez Martínez M. 2023. Botulism outbreak in Asian elephants: histopathological findings at necropsy. Poster at ESVP-ECVP Congress, August 2023, Lisbon. Elze, K. 1962. Botulism in an elephant (Über Eine Unter dem klinischen bild des botulismus verlaufend Erkrankung beim elephanten). 4th Verhandlungsbericht Internationalen Symposiums Erkrankungen Zoo und Wildtiere, Berlin, Akademie Verlag, pp. 259–271. Fowler M.E. 2006. Infectious diseases. In: Biology, Medicine and Surgery of Elephants, Ed. Fowler and Mikota, Chapter 11, Infectious diseases Garlt, C., Kiupel, H. and Ehrentraut, W. 1977. Botulism in elephants (Ein beitrag zum Botulismus bei elefanten). 21st Verhandlungsbericht Internationalen Symposiums ErkrankungenZoo und Wildtiere, Berlin, Akademie Verlag, pp. 207–211. Websites: FAO: https://www.fao.org/3/t0756e/T0756E03.htm American Association of Equine Practicioners (AAEP): https://aaep.org/guidelines/vaccination-guidelines/risk-based-vaccination-guidelines/botulism Botulism

Perineal hernia in elephants are rare, but have been described. One surgical treatment has been described. To non-infectious diseases Perineal hernia Compiled by Willem Schaftenaar, 2020 Definition : A perineal hernia is a disruption of the pelvic diaphragm musculature that allows contents of the pelvic canal and/or abdominal cavity to herniate into the perineal subcutaneous tissues. In elephants this condition presents as a large bulging mass below the tail. Diagnose : 1. Pressure on the bulging area sometimes results in urination. This is suggestive for the presence of the urinary bladder in the perineal subcutaneous space. 2. Rectal palpation: if the urinary bladder is present in the perineal subcutaneous space, the bladder may empty when pression is used by the hand through the rectal wall. 3. Transrectal and transcutaneous ultrasonographic examination: visualization of the urinary bladder, cervix uteri or parts of the uterus in the subcutaneous space definitely confirms a hernia perinealis. History The cause of this condition in elephants is unknown. Complications: insufficient emptying of the urinary bladder may predispose for urine retention. There are no reports of urinary infection in elephants due to this condition. The first report on a perineal hernia dates from 1967 (Stehlik, 1967): a 20 yr-old female Asian elephant showed an over time increasing swelling in the perineal area, which aggravated each time the elephant had to stand on its hind legs for performance. Kuntze described a second case in 1989 and the author hypothesized that the hernia in this 6-yr-old circus Asian elephant might have been caused by the act that forced the elephant to stand on its hind legs, while supporting its front legs on another elephant ( Kuntze 1989). During this act, a 30 cm diameter ball-shaped swelling was noticed in the perineal area. As soon as the elphant stood on 4 legs, the swelling disappeared. Four years after the elephant had stopped this circus act, the swelling had disappeared. Hernia perinealis in an adult Asian elephant in a North American zoo. Treatment In the 4 cases that I am aware of, clinical signs were limited and did not cause discomfort to the elephant. These elephants were not treated for this condition. There is only one report about surgical repair of the perineal hernia, as the perineal subcutaneous mass became larger over a period of 10 years (Myanmar, 2016). Treatment results In one case in a 4 years old female Asian elephant, only the urinary bladder was involved. This case was not treated and the condition resolved within the next 3 years (Bernhardine, 1988, Rotterdam Zoo). The surgical repair in the Myanmar case was reported as a succesful intervention. Click here for the report. References Kuntze A. 1989. Arbeitsbedingter Krankheitsbilder: Hernia perinealis, bursitis praepatellaris und Tyloma Olecrani bei Zirkuselephantinnen (Elephas maximus ). 1989. 31st International Symposium on Diseases of Zoo and Wild animals, Dortmund (Germany) 1989, 185-187. Oo Z.M., et al. 2016 Surgical treatment of a cervico-vaginal prolapse in an Asian elephant in Myanmar. Gajah 44, 36-39 Stehlik M. 1967. Über zwei Fällen von Fussleiden, einen Fall von Volvulus und einen Fall von Hernia Perinealis bei indischen Elephanten. Nineth International Symposium on Diseases of Zoo and Wild animals, Prague 243-247. To page top

This page directs you to a variety of non-infectious disease conditions in elephants: -bone fractures -botulism -colic -dental problems -dermatology -esophagus obstruction/impaction -esophagus spasm -hiccup -intoxication -lameness/orthopedic problems -mesenteric hernia -ophthalmology -perineal hernia -reproduction problems -tetanus -umbilical hernia Non-infectious diseases Bone fractures 'Hiccup' Botulism Clostridiosis Colic (abdominal pain) Dentistry Intestinal impaction Intoxication Lameness/orthopedic problems Mesenteric hernia Dermatology Edema Esophagus obstruction Esophagus spasm Ophthalmology Perineal hernia Reproduction problems Tetanus Umbilical hernia Clostridiosis I need your input to write these chapters: Bloat Constipation Neonatal problems Urinary/kidney problems Clostridiosis Tetanus Enterotoxemia Clostridioides difficile Malignant edema Black leg Clostridium novyi Botulism

This page describes eye problems in elephants and how to treat them. Blepharitis, conjunctivitis, cornea edema, keratitis, vitamin A deficiency, corneal ulcer, cataract, hypopion, uveitis, synechia, iris prolaps, and panopthalmitis. Ophthalmology Compiled by Dr. Khyne U Mar, DVM and Willem Schaftenaar, DVM Eye problems are common in elephants. They are often the result of trauma and present as superficial or deep cornea lesions and ulcers. Cataracts are also regularly seen in elephants. If the vision in one eye is reduced, the animal should be approached with care from that side. In a study in 1478 captive elephants (2956 eyes) in Thailand, 17.83% of the examined eyes from 369 elephants (24.97% of the total number of elephants) had anterior ocular abnormalities. The most common lesions in these examined eyes were frothy ocular discharge (5.85%), corneal edema (5.31%), and conjunctivitis (5.18%). In addition, epiphora, phthisis bulbi, other corneal abnormalities, anterior uveitis, and lens abnormalities were noted. Almost all lesions increased in frequency with age (Kraiwong, 2015). Regular ophthalmic examination in elephants should be included in their annual health check program. Early detection and treatment of any ocular abnormality may avoid the development of subsequent irreversible ocular pathology. Clinical examination overview and diagnostic techniques The clinical examination of the eye starts with the anamnesis (history) and observation of the animal. The eyelashes should be long in order to protect dirt and objects from touching the surface of the eye. They are located mostly superior to the eye and can be as long as 11 cm. The inferior eyelid has less and smaller (2 cm) lashes. A unique feature of the elephant eye is the lack of a lacrimal apparatus (lacrimal glands as well as nasolacrimal duct) and eye brows. Tear films simply flow towards the medial canthus and exit along a groove in the skin onto the face in Asian elephants (Wong et al. 2012). The area around the eyes is therefore often wet. A Schirmer tear test can be performed in elephants. In a research cohort of 80 healthy Asian elephants the mean value was 34.3+/- 1.7 mm/min with older elephants (>40 years) having higher values than younger ones (<20 years). The cornea should be clear, without any irregularities. The iris of an elephant varies in color from tan, yellow, brown or the combinations. Blepharospasm is a strong indication for ocular disease. Conjunctiva cultures can be taken, though the strong palpebrae can make sampling for culture a challenge. Ophthalmic anesthetics can be used safely in elephants and may facilitate clinical examination and allow ophthalmoscopic examination of the deeper ocular structures. The pupillary light response can be performed if the elephant trusts the clinician enough to approach the animal with a proper light source at the required short distance. This test should be performed in subdued light. The menace response can be performed if the animal allows the clinician at short distance by moving fingers towards the elephant's eye without causing air movement. The numerous hairs on the skin of the palpebrae are not true cilia or true eyelashes as they are not associated with the margins of the palpebrae (Wong et al 2012, J. Zoo and Wildlife Med., 43(4), pp 793-801). The lower eyelid is more developed and ascends to a greater degree than the upper lid descends (Suedmeyer, 2006). (Photo KUMar) The iris of an elephant can have several colors: tan, yellow, brown or a combination. (Photo: W.Schaftenaar) A white, circumferential ring, similar to the arcus senilis in man is noticed in 40+ yr Asian elephant (fat deposit or aging?). (Photo: KUMar) Fluorescein staining of the cornea may be difficult as the elephant will close its eye immediately when approached. A fluorescein strip can be placed in a 10 ml syringe with sterile water or saline; this solution can then be sprayed over the eye in a constant flow using a blunt small gauge needle. This should be sprayed on the eye from the medial or lateral side. It helps when at the same time a steady water stream is directed at the periocular skin, which may result in relaxation of the animal. After fluorescein has been sprayed on the cornea, the eye should be flushed with sterile saline to remove excessive fluorescin. If present, cornea defects will stain green under blacklight and even under regular light. Cataracts which appear as a white central spot and keratitis (diffuse, superficial cloudiness of cornea) are frequently seen in elephants. Vision can be checked by passing the light of a flashlight (or cell phone) from the ear over the eye to observe for a blinking reflex. Ophthalmoscopy in the untrained elephant can be quite a challenge, as the animal will usually not allow this kind of close examination that moreover uses a light source. However, the animal can be trained to allow ophthalmoscopy. The third eyelid or nictitating membrane is located at the ventro-medial aspect of the orbit. Inside the nictitating membrane, an oblong, flanged-shaped piece of hyaline cartilage supports the anterior palpebral aspect of the nictitating membrane. The harderian gland that is located here, plays a role in the lubrication of the cornea. Zeis's glands (modified sebaceous glands) are located in the margins of the lid. They produce an oily substance that helps lubricate the cornea. Blinking reflex The nictitating membrane in an Asian elephant (arrow).(Photo: KUMar) Blinking reflex using a smartphone's flash light in an Asian elephant with chronic keratitis. (Video: W.Schaftenaar) Ultrasonographic examination The clinical examination of the elephant's eye can benefit from transcutaneous ultrasonographic examination. The anterior eye chamber, the lens end the posterior eye chamber can be visualized using a 4-7 MHz convex probe (Bapodra et al. 2010). Following are descriptions of the anatomical components of the eye and the medical condition that may occur Eyelids Blepharitis is an inflammation of the eyelids than can be caused by trauma (rubbing), parasite infection or as part of a localized dermatitis. The accompanying symptoms are blepharospasm, epiphora (tearing that appears as wet skin area below the eye) and often photophobia. Sometimes lice (Haematomyzus elephantis ) or ticks (Amblyomma tholloni) can be found on the eyelids causing local skin lesions. Blepharitis in an Asian elephant. (Photo: KUMar) Small skin lesion caused by ticks (Amblyomma tholloni) (Photo: KUMar) Conjunctiva The conjunctiva is the tissue that lines the inside of the eyelids and covers the sclera (the white part of the eye ). It is composed of unkeratinized, stratified squamous epithelium with goblet cells , and stratified columnar epithelium . The conjunctiva is highly vascularized, with many microvessels . Conjunctivitis is an inflammation of the conjunctiva and is a common finding in elephants. In some cases small nodules and vesicles may be observed (lymphoid tissue on histology), possibly associated with chronic irritation. A conjunctivitis is often the result of trauma (hard object, dust, irritating liquid or smoke). Conjunctivitis is also seen in poxvirus infections. Conjunctivitis in an Asian elephant (From: Elephant care manual for mahouts and camp managers, FAO 2005 , Conjuctivitis and keratitis in an Asian elephant. Note the swollen mucosa. (Photo: KUMar) The conjunctival sac is a connection between the palpebral and bulbar conjunctiva. Under certain conditions (hypoproteinemia, trauma, insect bites or allergic reactions), a prolapse of this part of the cornea can develop, which protrudes like a mucosal sac between the eye and the lower eyelid. Prolapse of the conjuncitival sac in an Asian elephant. (Photo: KUMar) Cornea The cornea is transparent because it lacks cells and blood vessels and has no pigment. The cornea should always be wet thanks to a pre-corneal film tear. Oxygen and nutrients are available from the aqueous cornea tear film, the limbal capillary plexus and the palpebral conjunctival capillaries. Several disorders of the elephant cornea have been reported. Most of the corneal lesions seem to have a traumatic cause: trauma by rubbing, allergy by environmental irritants such as exposure to direct sunlight or continued exposure to dryness or small particles, e.g. dust, smoke, grass seed etc. that damage the corneal epithelium. Hypovitaminosis-A has also been suggested as a cause of cornea disorder as well as hypoproteinemia. Acanthamoebae Spp. has been identified in corneal swabs. It's presence has been associated with corneal ulcers (Dangolla, 2005). However, the protozoa was also found in swabs taken from healthy elephant eyes (Wijesekara, 2007). Corneal edema Corneal edema, also called corneal swelling, is a buildup of fluid in the cornea. It is caused by dysfunction of the endothelial membrane on the inner side of the cornea, that normally pumps fluid out of the cornea in order to keep it transparent and clear. This can happen after a blow to the eye or a puncture of the cornea (e.g. by small branches), or by contact with toxic substances. Cornea edema in an Asian elephant. (Photo: KUMar) Cornea edema in an Asian elephant. (Photo: KUMar) Cornea opacities - keratitis Opacities in the cornea are called keratitis and are very common in elephants. They present as whitish, "cloudy" areas usually in the central part of the cornea. It has been suggested that they are caused by trauma (thorns, heat, dust, and chemicals), direct sunlight or chronic dehydration. The cornea must be checked for foreign bodies. In severe keratitis, the entire cornea turns white. This reduces the vision of the animal to only being able to distinguish just between light and dark. This can be tested with the blinking reflex . In some cases, keratitis can be painful: the elephant shows blepharospasm and the third eyelid may be protruded (partly) over the eyeball. In that case involvement of the iris should be considered. It is recommended to perform cytology, aerobic bacterial culture, and sometimes fungal culture. When opacities are only found in the superficial epithelium, and dispersed over the entire cornea surface, it might be the result of hypovitaminosis-A (vitamin A is essential for the normal functioning of the corneal epithelium, including the production of the tear film). This condition is called "xerophthalmia". As fluid makes its way into the cornea it can accumulate and cause the formation of small bullae or "blisters." This is called bullous keratopathy. If the blisters break or rupture, a corneal ulcer will result. Mild, superficial opacity in the central area of the cornea in an Asian elephant (keratitis). (Photo: KUMar) To page top Diffuse, superficial opacities spread over the entire cornea of an Asian elephant, possibly caused by hypovitaminosis-A (xerophthalmia). (Photo: KUMar) Mild keratitis in an Asian elephant. (Photo: KUMar) Severe keratitis involving the entire cornea of an Asian elephant. (Photo: KUMar) Severe keratitis with protrusion of the third eyelid in an Asian elephant. This could be an expression of pain, in which case iris involvement should be considered. (Photo: KUMar) Corneal ulcer A cornea ulcer is an open sore on the cornea. The epithelial outer layer and the middle layer of the cornea (stroma) are disrupted. This condition is also called a melting corneal ulcer. Usually the primary cause is trauma of the cornea. This traumatic lesion can become infected by bacteria (Pseudomonas, Neisseria spp, fungi and other microbes. This condition is very painful a nd blepharospasm is often seen. The elephant may be rubbing the area around the affected eye against an object. There may be protrusion of the third eyelid. An ulcer is usually the result of trauma. Treatment of keratitis with NSAID's or glucocorticosteroids increases the risk of ulceration. As a reaction to the ulcer and to repair the lesion, blood vessels will grow into the stroma of the cornea, visible as small red lines, sometimes forming a network of small vessels. This process takes several weeks. When the cornea surface has been repaired, the remnants of these blood vessels will be visible as white connective tissue strands. The major risk in an ulcerated cornea is perforation of the entire cornea, which will result in loss of the ocular fluids and complete loss of the eye. When blood vessels fail to grow towards the ulcer, the ulcer remains in an unchanged form as an indolent corneal ulcer, needing a special treatment. Two manifestations of a severe keratitis and cornea ulcer with a prolapse of the iris in an Asian elephant. (Photo: KUMar) Hypopyon Hypopyon keratitis is an accumulation of pus (heterophils and fibrin) in the anterior eye chamber (between cornea and lens). It is accompanied by profuse discharge and signs of ocular pain. Ultrasonographic examination may be helpful for diagnosing pus in the anterior chamber. One case report describes the treatment of hypopyon in an Asian bull elephant. Hypopyon and uveitis have been described in a case of leptospirosis (Fowler. 2006. Infectious diseases. In: Fowler and Mikota, 2006, 403). Hypopyon Iris and uvea The iris is a diaphragm that regulates the influx of light. It is a very vulnerable structure that consists of two layers: the outer (anterior) pigmented fibrovascular layer (known as stroma, which lacks an epithelial layer) and the inner (posterior) surface covered by a heavily pigmented epithelial layer that is two cells thick (the iris pigment epithelium). This anterior surface projects as the dilator muscles. The high pigment content of the iris blocks light from passing through to the retina, restricting it to the pupil. The outer edge of the iris, known as the root, is attached to the sclera and the anterior ciliary body . The iris and ciliary body together are known as the anterior uvea . Uveitis Any lesions in the anterior part of the eye can result in damage to the iris. Parts of the affected iris may come into contact with the inner layer of the cornea (anterior synechia) or the lens (posterior synechia). If there is also a corneal ulcer, the iris may prolapse through the ulcer (iris prolapse). Iris lesions are considered to be very painful in all animal species. These conditions need immediate veterinary attention. Lesions of the iris and uvea are called uveitis . If only the anterior part is involved, we call it iritis . In reality it will be hard to distinguish these conditions in elephant ophthalmology, unless proper ophthalmoscopy can be performed under sedation or general anesthesia. Lens The lens is a transparent biconvex structure in the eyes that, along with the cornea , helps to refract light to be focused on the retina . Any lesions of the lens will result in white discoloration and loss of transparency (cataract). This is seen as a white area in the central pupillary space. Young cataracts will appear as cloudy structures. A mature cataract appears as a completely white pupil. A complete, mature cataract will reduce the vision of the elephant which may finally result in complete blindness of the affected eye. When an elephant is approached on the side of the blind eye, the clinician should be aware of the compensating behavior of the elephant, when it tries to keep its functional eye on the investigator. Cataracts are quite common in Asian elephants in range countries. One paper notes that 6-8% of the elephants kept in Sri Lanka suffer from this condition (Kuruwita, 1991). Several causes of cataracts are known in other animal species: trauma, overexposure to sun light, deficiency of vitamin A, C, E or riboflavin, diabetes and dehydration. Often the cause of a cataract in elephants cannot be determined. Early stage of a cataract in an Asian elephant. (Photo: KUMar) Advanced stage of a cataract in an Asian elephant. (Photo: KUMar) Advanced stage of a cataract in an Asian elephant. (Photo: KUMar) Panopthalmitis and phthisis bulbi Panophthalmitis is inflammation of all layers of the eye including the intraocular structures. It has been documented in nine eyes postmortem during a field study of eye lesions in African elephants ( McCullagh, 1969). Phthisis bulbi is a shrunken, non-functional eye. It may result from severe eye disease, inflammation or injury. Phthisis bulbi after chronically infected cornea ulcer. (Photo: KUMar) Subdermal injection of Plancentrex (0.1 mg/ml) in an Asian elephant with uveitis. (Photo: KUMar) Summary of the most frequently used drugs in ophthalmology Standard frequency of treatment applications: 3-5 per day Antibiotic treatment should be based on sensitivity test Flushing with 0.9% NaCl solution is recommended before every topical drug application The elephant's eye can be flushed using a long, small diameter tube place on a syringe. (Photo: KUMar) Treatment options in elephant ophthalmology Blepharitis: Treatments of blepharitis in elephants have not been described in the literature. A similar approach as in other mammals is recommended: elimination of the cause (parasites, dermatitis) and flushing the eye (see photo below) with saline solution, 3-5 times a day. Conjunctivitis, prolapse of the conjunctival sac : elimination of the cause and flushing the eye with saline solution, 3-5 times a day and antibiotic ointment, 3-5 times a day. Corneal edema: flushing with a hypertonic saline solution, 3-5 times a day. Keratitis in early stage: flushing with saline solution, 3-5 times a day, antibiotic ointment, 3-5 times a day. If there is no ulceration, topical application of 0.1% dexamethasone eye drops may be used; be aware that corticosteroids will stop the regeneration of the epithelial cells. Chronic keratitis: treatment will have no effect. Xerophthalmia: oral vitamin A supplementation. Corneal ulcer: flushing with saline solution, and topical application of antibiotic eye ointment 3-5 times a day. Topical application of Diclofenac sodium 1% eye solution may help reducing the pain. Promising results of the use of autologous serum have been reported (Janyamethakul, 2015), applied twice daily. Preparation of autologous serum: Five 10 ml. syringes were used to collect a total of 50 ml. Then, the blood was allowed to clot for 2 hours at room temperature before being centrifuged at 3,000 rpm for 15 minutes. The separated serum was collected (about 20-25 ml.) into a sterile container to which 1 mg. of gentamicin was added. The autologous serum was then aliquoted into sterile tubes, each containing 3 ml. Additionally, the serum was stored at 4°C and used within 7 days. Topical treatment with acetylcysteine (0.02%) was used in case of a corneal abscess along with gentamycin and atropine (Pipitwanichtham, 2023). Other treatments attempts that have been tried: Indolent (non-healing) corneal ulc ers are hard to treat. Debridement of necrotic corneal stro ma should be considered. This can be done by using a cotton tip, or in more severe cases the abnormal cornea tissue can be scraped using a corneal spatula. Theoretically, after the debridement, the cornea should be protected by a contact lens as used in horses. This has been repo rted once in a 44 yrs-old Asian elephant, in which case the lens was lost soon after application. In elephants flushing the eye and applying antibiotic eye ointment and autologous serum is probably the only possible post-debridement treatment. Stem cell application: pr omising results were seen at the Elephant Conservation Center Lampang (Thailand). Although never reported in elephants, the application of a few droplets of cyano-acrylate might be an alternative for a contact lens in elephants. Hypopyon: pain relief (NSAID), systemic antibiotics (DDX: leptospirosis!). Uveitis and Synechia: Atropine sulfate eye ointment (1%), 4-6 times a day, is a commonly used mydriatic drug in horses. It may stabilize the blood-aqueous barrier, reducing vascular protein leakage, minimizing pain from ciliary muscle spasm, and reducing the chance of synechia formation by causing pupillary dilatation. Pupil dilation is an indicator for the drug to be effective on the ciliary muscles. In horses even topical atropine has been shown to prolong intestinal transit time, reduce and abolish intestinal sounds, and diminish the normal myoelectric patterns in the small intestine and large colon of horses. Whether this also applies to elephants is unknown. Subdermal injection of placental extract (Placentrex®) is a common treatment for uveitis, hypopyon and corneal opacities in elephants in Asia (Suedmeyer, 2006). See also photo below. Iris prolapse: systemic NSAID, flushing with saline solution, 3-5 times a day. As the cornea is perforated by the prolapsed iris, the elephant should be treated systemically with antibiotics. Cataract: only 2 cases of (mature) cataract removal by phaecoemulsification have been reported (cataract surgery-UK and cataract surgery-USA). However, artificial lenses to replace the removed lens contents are not available. The significant lens instability (first noted following the initial stages of surgery in the USA-case, i.e., during creation of the anterior capsulorhexis) prevented implantation of an intraocular lens implant. See for more detailed information the references below (Cerrata, 2019 and Manchip 2020). Panophthalmitis: Enucleation is the only treatment indicated for this condition. However, there are no published data on the treatment of panophthalmitis. Placentrex Flushing References and further reading: Bapodra P, Bouts T, Mahoney P, Turner S, Silva-Fletcher A, and Waters M. 2010. Ultrasonographic examination of the Asian elephant (Elephas maximus) eye. Journal of Zoo and Wildlife Medicine , Vol. 41, No. 3, 409–417. Cerreta, A.J., McMullen Jr R.J., Scott, H.E., Ringenberg, J.R., Hempstead, J.E., DeVoe, R.S., Loomis, M.R., and Minter, L.J.. 2020. Bilateral Phacoemulsification in an African Elephant (Loxodonta africana). Hindawi Case Reports in Veterinary Medicine Volume 2019, Article ID 2506263, https://doi.org/10.1155/2019/2506263 or click here to download the manuscript. Dangolla A, JS Edirisinghe and ID Silva (2005). Association of Acanthamoeba with a corneal ulcer in a captive elephant (Elephas maximum maximus). Proceedings of 57th Annual Convention and Scientific Sessions of the Sri Lanka Veterinary Association. 33pp Fowler M. 2006. Infectious diseases. In: Biology, Medicine and Surgery of Elephants, Ed. Fowler and Mikota, 148. Janyamethakul T, Moleechat P, Gohain R, Somgird C, Pongsopavijit P, and Wititkornkul B. 2015. Efficacy of Autologous Serum as An Adjunct Treatment for A Melting Corneal Ulcer in A Captive Asian Elephant. Thai Journal of Veterinary Medicine: Vol. 45: 2, Article 18. Kraiwong, N., P. Sanyathitiseree, K. Boonprasert, P. Diskul, P. Charoenphan, W. Pintawong and A. Thayananuphat (2016). "Anterior ocular abnormalities of captive Asian elephants (Elephas maximus indicus) in Thailand." Vet Ophthalmol 19(4): 269-274. Kuruwita VY and Abeysinghe AB. 1991. Surgical correction of blindness due to mature cataract in a domesticated Asian elephant. International Seminar on Veterinary Medicine in Wild & Captive Animals, Bangalore, India, November 8 to 10, 1991; 23 Manchip, K.E.L., Sayers, G., Lewis, J.C.M., and Carter, J.W. 2019. Unilateral phacoemulsification in a captive African elephant (Loxodonta africana). Open Veterinary Journal, (2019), Vol. 9(4): 294–300. ISSN: 2218-6050 (Online) DOI: http://dx.doi.org/10.4314/ovj.v9i4.3 . or click here to download the manuscript. McCullagh, K.G. and Gresham, G.A. 1969. Eye lesions in the African elephant (Loxodonta africana). Res Vet Sci 10(6): 587–589. Pipitwanichtham S, Dittawong P, Meetipkit P, Sitdhibutr R, Pattanapon N, Kasornsri M, Phetudomsinsuk K, Thongtip N, Sripiboon S. Case report: Corneal stromal abscess in a captive Asian elephant: diagnosis and treatment regimes. Veterinary Integrative Sciences 2023; 21(3): 693 - 703 DOI; 10.12982/VIS.2023.050 . Suedmeyer Wm. K. 2006. Special senses. In: Biology, Medicine and Surgery of Elephants, Ed. Fowler and Mikota, 399-403. Use of a contact lens for horses in an Asian elephant (PDF) Wijesekara PNK, Bandara KAPA, Dangolla A, Silva ID and Edirisinghe JS. 2007. Incidence of Acanthamoebae Spp . in the eyes of a group of captive elephants in Sri Lanka. Conference: International Elephant Conservation & Research Symposium Florida USA At: Orlando, Florida USA, November 2007. Wong MA, Isaza R, Cuthbert JK, Brooks DE and Samuelson DA. 2012. Periocular anterior adnexal anatomy and clinical adnexal examinaton of the adult Asian elephant (Elephas maximus) . Journal of Zoo and Wildlife Medicine , Vol. 43, No. 4, pp. 793-80. To page top

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