Back to dermatology To reproduction Back to dermatology Case report Vaginal vestibulotomy and wound treatment Date: 1993 Place: Rotterdam Zoo Data provided by: Willem Schaftenaar HISTORY An uneventful first pregnancy (677 days) in a 29 years old Asian elephant ended in complete stagnation of the birth process. A 20x30 cm piece of fetal membrane tissue was found in the enclosure. Over 100 hours of strong labour activities did not result in progress of the parturition. Rectal palpation proved that the calf was in backwards position. Unfortunately ultrasonography equipment was not available. The presence of the amniotic sac was visible as a bulging below the anus. Labour activities stopped at that point. Total serum calcium level was 2.44 mmol/l (in 1993 this was still wrongly considered within normal ranges). T he animal was chained and 50 IU of oxytocin s.c. to stimulate uterine contractions. T he calf could easily be pushed backwards in between contractions (which nowadays is considered a sign of hypocalcemia!). No reactions of the calf were felt during these manipulations. The animal responded well to oxytocin. The uterine contractions and labor activities intensified during the next 30 min, but no progress was made. Two hours after the dministration an i.v. infusion of 750 ml of Ca- Mg-borogluconate was administered, containing 12 g calciumborogluconate. Another 50 IU of oxytocin s.c. was given at the same time. As before, the induced labour activities did not result in progress of the parturition. Again 2 hours alter, 50 IU oxytocin was given slowly IV, resulting in strong labour activities. One arm was brought into the vaginal vestibulum and the amniotic sac was cut using a vinger knife and a rubber rumen tube was advanced through the vestibulum and the tip of the tube was placed between the feet of the calf. Through this tube approximately 2 L of a lubricant was brought into the birth canal. SURGERY Local anesthesia was performed at 1700 hr by administering 5 injections of 20 ml lidocaine 2% + noradrenaline intra-and subcutaneously in the midline of the perineum, starting 5 cm ventrally of the anus, with an interval of 10 cm. Epidural anesthesia was not used, but new insides have proven that this is an important method to reduce movement of the tail and decreases pain perception in the perineal region. The perineum was brushed with a povidone iodine soap (Betadine scrub, Dagra Pharma B.V., 1112 AX, NL). A 25 cm long incision was made in the midline, starting 5 cm below the anus. A rubber rumen tube that was inserted retrograde into the birth canal. The vestibulum wall was incised over this tube just below the anus. This incision was enlarged ventrally to a distance of 25 cm. The hind legs were not visible at that time and chains had to be fitted blindly. Parts of the thick amniotic sac had to be cut away for better attachment of the chains. No reaction from the calf was observed during these operations. The chains attached to the calf’s hind legs were initially passed through the distal part of the vulva in an attempt to pull the legs through the natural birth canal. Pulling the chains essentially horizontally caused too much irritation on the vulva, so this procedure was abandoned. The incision was then enlarged ventrally to 37 cm. Pulling at the chains by 4 people resulted in advancement of the legs throught the surgical opening. The legs presented in horizontal position next to each other but when the tarsus were outside the opening, the calf got stuck in the maternal pelvic cavity. Standing back to back, two persons pushed the calf as far as possible back into cranial direction of the birth canal. When accomplished, e ight people, four on each hind leg, were allowed to pull on the chains: by pulling on one leg at the time and changing the direction during 45 min, the calf was rotated 90° and could finally be extracted. During the extraction, it became evident that the umbilical cord was twisted twice around the hind legs, which had probably resulted in the death of the calf. It is well known from cattle and horse obestetry, that a dead fetus is often associated with dystocia, as the longitudinal rotation of a fetus is facilitated by movements of the fetus during its passage through the birth canal. TREATMENT of the SURGICAL WOUND The surgical wound was closed in 3 layers. The vestibulum wall was closed using atraumatic Dexon 0. A nonperforating continuous suture, tied after every fifth stitch was made. No subcutaneous tissue was available for suturing. The skin wound was flushed with 10% diluted povidone iodine. The endodermis was sutured using atraumatic Dexon 1 with the same type of stitch. The skin was closed with Mersilene 4 using 27 single stitches. The wound was sprayed with U.S.P. wound spray. Amoxicillin was given at 5 mg/kg i.m. SID for 4 days, when reatment was changed to enrofloxacin given at a dose of 1.33 mg/kg i.m. This treatment was continued until day 11 when the entire wound spontaneously opened. The wound was sutured again under local anesthesia and xylazine sedation on four occasions at 8-12 wk intervals. The first attempt was made 8 wk after the vestibulotomy. The animal was given 480 mg zuclopentixol p.o. 1 hour prior to surgery. This seemed to chang her behavior in an undesired way; she became more alert and aggressive than was expected. Granulation tissue was removed and the wound was closed in two layers, using the same material used for the initial sutures. The wound opened again within a week. The wound was cleaned again completely and the mucosa was separated from the underlying tissue. A nonperforating continuous stitch with thicker suture material, was used to close the wound; monofilamentous PDS-1 was used for the vestibulum, and braided PDS-1 for the submucosal/subcutaneous tissue. The skin was closed with a continuous mattress stitch with sheep’s Bühner tape using a modified Gerlach’s needle. Each skin perforation was made 2-3 cm from the incision and protected by 3 mm thick rubber rings (3 cm diameter). The animal remained hobbled on both hind legs during the following 10 days. During this period she received 500 mg acepromazine (Vetranquil granulate, Sanofi, 3144 EG, NL) p.o. b.i.d., 50 mg butorphanol p.o. b.i.d. and 20 g amoxicillin p.o. b.i.d. The wound opened partly after a few days. Twelve weeks later a third attempt was made to close the two remaining fistulas. Only the mucosa of these vestibulum fistulas (5 cm and 0.8 cm respectively) were closed in three layers, using PDS-1. Again these wounds opened after a few days. One more attempt was made to close the remaining fistulas, which were healing per secundum. A modified balloon catheter was inserted into the urethra during this intervention. The orificium urethrae could be reached by hand, just at the edge of the horizontal part of the birth canal. The balloon was filled with 50 ml of water. Only the vestibulum mucosa was stitched to reduce infection of the wound by accumulation of purulent material in the subcutaneous space. During the following 2 days all urine was passed through the catheter. On the third day, the urine passed through the wound again. The catheter has never been recovered. No more attempts to suture the wound were made. Treatment results In the following 1.5 year the wound healed per sucundam to date two fistulas of 10 mm and 2 mm respectively. Aspect of the wound immediately after closing the wall of the vaginal vestibulum Aspect of the wound 11 days after first attempt to close the wound. Immage of the sutured skin immediately after the second attempt to close the wound. Separating the wall of the vaginal vestibulum from the skin before suturing the vestibulum for the 3rd time. Immage of the wound 2 weeks after the second attempt to close the wound. The use of Bühner tape and rubber tubes to prevent the skin sutures from cutting into the skin during the 3rd attempt to close the wound. COMMENT of the AUTHOR Closing the wound after a vaginal vestibulotomy does not seem to be rewarding. The wound healing capacity of the elephant skin is enormous. To my knowledge, in all reported cases the skin sutures did not hold and the skin wound finally closed per secundam ( Miller et al. 2004 ). Closing the vaginal vestibulum might be worth attempting, as it may result in partial or complete healing of the vestibulum wound (Thitaram et al. 2006). Nevertheless, leaving the entire wound open will finally result in excellent healing per secundam. However, the epithelium of the vaginal vestibulum may fuse before the skin wound is closed. This condition requires minor surgical intervention, by separating the 2 layers and dissecting a small strip of the edges. See also the case report of the fetotomy . References Schaftenaar, W. 1996. Vaginal vestibulotomy in an Asian elephant (Elephas maximus ). Proceedings Am. Ass. Zoo Vet. 434-439. Chandrapuria, V.P., Shrivastava A. B., Agrawal S, and Agarwal S. 2014. Vaginal Vestibulotomy in an Asian Elephant. Gajah 40 (2014) 39-41 Merckt et al. 1985. Episiotomy, a possible obstetrical intervention in the elephant cow. Dtsch Tierarztl Wochenschr, 1985 Oct 8;92(10):428-32. Miller M., Neiffer D., Schmitt D., Weber M., Robbins P.K., Stetter M., Fontenot D., Fleming G., Miller G., and Maluy P. 2004 Medical management of dystocia and vestibulotomy for removal of a retained fetus in an African elephant. In: International elephant Research Symposium, Fort Worth (Texas) organized by The International Elephant Foundation. Pg 14-17. Thitaram C. et al. 2006. Dystocia following prolonged retention of a dead fetus in an Asian elephant (Elephas maximus ). Theriogenology 66,1284–1291. EAZA Veterinary guidelines for reproduction-related management in captive female elephants. 2020 . EAZA reproduction guidelines To page top

A 1 yr-old Asian elephant suffered of colics as a result of a (traumatic) hernia mesenterialis. A torsio of the small intestines was incarcerated in the hernia. Consequently the intestine ruptured. The calf died due to acute peritonitis. To non-infectious diseases Case report Hernia mesenterialis and intestinal rupture Date: 2002 Place: Rotterdam Zoo Data provided by: Willem Schaftenaar History Species: Asian elephant Accommodation: Zoo, free contact Age, gender: 1 year, male Five years before this episode, a 3 yrs-old calf at the same zoo had died of EEHV1a . The calf (300 kg estimated BW) was heavily hit on its abdomen by a herd mate. Two days later (Day 1) it became very lethargic and stopped drinking from its mother. Day 1 08:30: Very lethargic, not eating. Laying flat on the ground, while kicking with his hind legs ( colic ). Sometimes standing with the mouth widely opened. Conjunctivae: slightly congested. Tongue: normal color. No edema on head or shoulders. Defense musculaire: normal. Rectal temperature: 36.8°C A standing sedation using xylazine (0.1 mg/kg BW IM for the calf, 0.08mg/kg BW for the dam) was performed in both the affected calf and its mother. As soon as sedation started, the calf was brought to its mothers mammary glands and it started drinking from the mother. EDTA and full blood samples were taken and rectal fluids were given during the sedation. Rectal palpation: only one handfull of soft feces in distal part of the rectum. The rectal wall is very dry. Urine sample: all values (dipstick) within normal ranges. Blood sample collected. Hematology and blood chemistry results were all within normal ranges. EDTA whole blood sample submitted for PCR on EEHV. Results: PCR-positive EEHV1a. Rx: 6 ml Finadyne (flunixinemeglumine 50 mg/ml, NL1726) i.m. 15 ml Baytril 10% (enrofloxacin 100 mg/ml, NL3489) i.m. 3000 mg famciclovir mixed with 15 ml utrasound gel per rectum. Calf during standing sedation and suckling from its mother. Note the penis relaxation, typical for alpha-2-agonist sedation. 16:30: No change. Not eating, laying. Less signs of colics. Rx: 1500 mg famciclovir mixed with 10 ml ultrasound gel per rectum. 23:00: Animal is lethargic. Laying down most of the time. Rx: 1500 mg famciclovir mixed with 10 ml ultrasound gel per rectum. Day 2 Slightly alerter than before. Treatment was continued similar to day 1. Day 3 08:30 Alerter, but no attempts to nurse from its mother. Rx: 15 ml Baytril 10% (enrofloxacin 100 mg/ml, NL3489) i.m. 1500 mg famciclovir mixed with 10 ml ultrasound gel per rectum. 16:00 Agian very lethargic. Has not eaten or nursed at all. No feces nor urine produced. Standing sedation (calf and dam, see day 1). Again the calf was drinking well during the sedation. Also defecating and urinating. Firm feces. Rx: 1500 mg famciclovir per rectum dissolved in 20 ml water. 600 ml Amynin (per ml: 50 mg glucose anhydrate, electrolytes, aminoacids and B-vitamins, NL 4137) per rectum. Blood and urine samples collected. All values within normal ranges. EDTA: EEHV-PCR signal much lower than day 1. Day 4 08:00 Alerter, has not been laying excessively long during the night. Rx: 1500 mg famciclovir per rectum (dissolved in 20 ml water). During the morning the animal has been drinking spontaneously from his mother. Treatment similar today 2. Day 5 09:00 Leaning against the poles. Rx: 1500 mg famciclovir per rectum (dissolved in 20 ml water). Keepers think his behaviour is about the same. Is drinking water from the hosepipe. Some normal feces manually removed from the rectum. 16:00 Still leaning against the poles but sometimes giving a more alert impression by moving his tail. Rx: 1500 mg famciclovir per rectum (dissolved in 20 ml water). Standing sedation (xylazin 0.1 mg/kg IM). Drinking from his mother. Day 5 08:00: Very lethargic; did not drink during the night. Tympanic, bilateral; intestinal obstruction suspected. Some dry feces were collected from the rectum. Rx: 1500 mg famciclovir per rectum (dissolved in 20 ml water). 6 ml Finadyne (flunixinemeglumine 50 mg/ml, NL1726) i.m. 15 ml Baytril 10% (enrofloxacin 100 mg/ml, NL3489) i.m. During the day the condition of the animal deteriorated. 14:00: sedated with xylazine (0.1 mg kg IM). Blood sample collected - heparin and EDTA and fluride. Rectal palpation: balloon-like intestines. The calf suddenly regurgitated and threw up stomach content. Rectal fluids were given. At 15:00 the animal died. Necropsy Necropsy hernia mesenterialis 1) Cause of death: * Rupture of the ileum resulting in peracute peritonitis. * Mesenteric hernia. * Intestinal mesentery, small intestine (jejunum), ileum: Venous infarction, acute, marked, with venous and lymphatic thrombosis, fibrinoid arterial necrosis, and interstitial haemorrhage and necrosis. * Intestinal mesentery, small intestine, hepatic capsule, pancreas: Peritonitis, fibrino-purulent, diffuse, peracute, moderate, associated with bacterial infection. 2) Significant diagnoses: * Liver: pericholangitis, eosinophilic, diffuse, chronic, severe, with bile duct hyperplasia and portal fibrosis. * Liver: hepatitis, granulomatous, eosinophilic, multifocal, chronic, moderate. 3) Incidental diagnoses: * Heart: haemorrhage, subendocardial, epicardial, multifocal, acute, mild. * Lung: pulmonary oedema, diffuse, acute, mild. * Adrenal cortex: adrenocortical necrosis, multifocal, acute. Cyanosis of the tongue and epicardial hemorrhages that are seen in EEHV-HD were also present in this case. They are the result of circulatory shock and are not pathognomitic for EEHV-HD. The intestinal contents was found freely in the abdomen. The hernia and the torio of the mesenterium is well demonstrated on the last photo. Conclusion Initially, when the PCR-result was positive for EEHV, EEHV was considered the cause of the disease and anti-EEHV treatment was started. Based on previous findings, the mother of the calf was assumed to be a carrier of EEHV1. However, the normal hemogram was not in line with what was seen in other EEHV-HD cases. At necropsy, multiple hemorrhages were seen in almost all organs, which is also seen in EEHV-HD. However, the predominant pathological conditions (hernia mesenterials, volvulus, torsio and rupture of the ileum were the cause of death. The presence of EEHV1a can only be explained as a virus reactivation due to a heavy stress respons of the calf in relation to the intestinal problems. Peritonitis in elephants has only been mentioned in a paper describing the presence of unrelated dermoid cysts in an Asian elephant (Wayn, 1991). References Wayne I., Anderson & Danny W. Scott. 1991. Epidermoid Cysts in the Skin of an Asian Elephant (Elephas maximus). Vererinary Dermarology. Vol. 2, No. 3/4, pp. 171-172. To page top

A 7 yr-old Asian elephant developed ventral edema when it suffered a clinical episode of salmonellosis. To Salmomellosis Case Report Next case Salmonellosis in 7 yr-old Asian elephant Place: Dak Lak elephant Conservation Center Vietnam Date: 2017 Data provided by: Van Thinh Pham, DVM History During the rainy season, a 7 yr-old orphan Asian elephant bull showed severe diarrhea, lethargy and anorexia for 1 week before it developed abdominal edema. It was kept with another orphan elephant in the open air in a range country. No parasites were found in fecal samples. Bacterial culture from feces showed growth of Salmonella typhymurium. Treatment Before Salmonella was cultured, the elephant was treated with trimethoprim sulpha (TPS) and metronidazole (dosages unknown). Based on the sensitivity found in the antibiogram, an oral antibiotic treatment with ciprofloxacin (5 mg/kg BW BID) was given for 5 days. Treatment results 36 hours after the start of the antibiotic treatment, the elephant resumed eating. feces were normal again after 3 days. The edema resolved within 7 days. To page top

Treatment of severe skin wounds in an adult female Asian elephant in Vietnam To dermatology Case report Skin lesions in an adult Asian elephant Place: Dak Lak elephant Conservation Center Vietnam Date: 2018 Data provided by: Van Thinh Pham, DVM, Susan Mikota, DVM and Willem Schaftenaar, DVM History Adult female Asian elephant, chained on its hind leg for >10 days while deprived of food and water for prolonged periods. This had resulted in a large deep wound on the left hind leg and a smaller wound on the right hind leg. The wound on the left hind leg involved damage to the underlying ligaments, expressed in a lateral deviation of the leg distal to the tarsus and overstretching of the tarsal joint. The wounds were extremely dirty and covered by necro-purulent materials. Treatment The elephant was sedated using xylazine (0.08 mg/kg IM) The wounds were debrided using scalpel blades, scissors and cotton gauze. For several weeks the wounds were flushed BID with clean water, sprayed with Betadine solution. After each treatment, honey was applied on the wound using a soft brush. The largest wound after flushing with water, spraying with Betadine and application of honey. Treatment results In the course of 8 months the wounds healed completely. The lateral deviation of the distal part of the left hind leg remained and caused moderate instability of the tarsal joint. To page top

Botulis has been described sporadically in elephants. This case report describes an outbreak of botulism in a bachelor group of Asian elephants. Fife out of 6 elephants died within a few days after showing initial neurological symptoms. The source of the toxines was found in the silage that was used as a food source. To non-infectious diseases Case report Clostridium botulinum in a bachelor herd of Asian elephants Date: 2017 Place:Spain (zoo) History A group of 6 juvenile Asian elephants had been kept under Mediterranean climate conditions for several years without major disease issues. During springtime, 5 out of these 6 elephants fell ill within 1 week and died days after showing first signs of illness. The major clinical signs consisted of gradually increasing general weakness, shivering, mild salivation, inability to stand and properly use their trunk. Three of the affected elephants died within 3 days after onset of clinical signs. The other 2 elephants were humanely euthanized as there were unable to stand up. The animals were fed ryegrass silage, grass and pellets. Clean drinking water was available, but the animals had also access to pools with water of questionable quality . The only unaffected elephant was the subordinate animal in the group, having less access to favorite food items. Blood parameters were within normal ranges. Several zebras that were kept in another part of the zoo showed neurological symptoms (shivering, shaking, paresis, inability to stand) and some of them had died too. One of the affected elephants leaning against the wall in the early stage of the disease. Zebra at the same zoo in the same period suffering of ataxia, trembling and paresis after feeding on ryegrass silage contaminated with Clostridium botulinum . Paralytic Asian elephant in lateral recumbancy, unable to bring food items into its mouth after feeding on ryegrass silage contaminated with Clostridium botulinum Treatment Symptomatic treatment was given in the form antibiotics, IV infusions and rectal water administration. The diagnose could only be made several days after necropsy, as the toxicology samples had to be sent abroad. Diagnostic results Necropsy results: Multifocal hemorrhages, edema in the heart. No evidence of virus infection. No pathogenic bacteria found. Toxicological examination of the silage revealed the presence of vomitoxin and zearalenor (see below). Click here to view a poster on the histological changes seen in this case report. Toxicology results: Silage: Sulphite reducing Clostridium: 800 cfu/gr Vomitoxin: pos. Aphlatoxin: neg. Fumotoxin: neg. Ocratoxin: neg. Zearalenor: low pos. Toxin T2: neg Stomach and intestinal content: Clostridium botulinum toxin found in stomach contents of elephants and zebras and silage (mouse bio-assay) Subtyping of the strain was not performed. For background information about botulism: click here To page top

Miscellaneous

Elephant dentistry is an important part of elephant medicine. Molars may develop in the wrong direction resulting in abnormal wear. Parts of old molars may dealy in falling out, resulting in pain. Tusk issues are common in Asian bulls and both genders of Arican elephants: fracture, fussure pulpitis, sulcus infection. To non-infectious diseases Dentistry TUSKS MOLARS Fissure/longitudinal crack Molar tooth issues Tusk fracture Pulpitis (needs your input) Sulcus trauma after fracture Sulcus infection Supernumerary tusk Tush loss (female elephant) Tusk extraction (needs your input) https://www.mondulkiriproject.org/blog/elephant-teeth/ To page top

Sharing clinical cases amongst elephant veterinatians and caretakers will increase our knowledge, so we can treat elephants better. Knowledge Elephant medicine is a specialism that is usually obtained after many years of working with elephants. Compared to the amount of literature that is available for equine practicioners, the amount of literature about elephant medicine is very limited. Recognition On this website we collect clinical data from field workers in range countries and zoos. By showing these experiences on this website, we hope to help you, veterinarians and elephant care takers, when you are confronted with a clinical problem. Maybe you recognize similar symptoms and syndromes in your sick animal and learn how your case might be treated. Sharing By using the contact button, you can share your information and questions with us, so we can add new opinions to the existing case reports or add a new report. WHY THIS WEBSITE?

EEHV hemorrhagic disease in elephants is often fatal as a result of DIC. Antibody assays and PCR monitoring may help to treat affected elephants in an early stage. This page describes the virus, the disease, its treatment, plasma transfusion, cross matching and standing sedation. To infectious diseases Elephant Endotheliotropic Herpes Virus-Hemorrhagic Disease (EEHV-HD) Compiled by Willem Schaftenaar History: EEHV-HD is caused by a delta-herpesvirus. The virus has evolved with the elephant species and is older than the currently living elephant species. Most (if not all) adult elephants are latently infected with EEHV. Young elephants between 1 and 9 years of age can be susceptable for an often fatal syndrom: EEHV-Hemorrhagic Disease. It is hypothesized that the long half-lifetime of maternal antibodies (EEHV maternal antibodies can circulate for up to 36 months in a calf) protects the calf against developing this syndrome. If this is true, it means that calves need to be exposed to EEHV during the phase in which antibodies are decreasing, but still protecting the calf. Fatal cases in Asian elephants have been reported over 20 times more than in African elephants. One of the hypotheses is that African elephant are shedding the virus much more frequent than Asian elephants, which offers a better opportunity for the calf to build up a solid immunity during the period that it is still protected by maternal antibodies. Asian elephants can carry EEHV1a, EEHV1b, EEHV4 and EEHV5, of which EEHV1a has caused the vast majority of the fatal cases. African elephants can carry EEHV2, EEHV3a, EEHV3b, EEHV6 and EEHV7. EEHV3 and EEHV6 have been associated with fatal cases, while the other African EEHV-subtypes are associated with lymphoid nodules in lungs and skin of African elephants. There is one report of a fatal case caused associated with EEHV3 in an Asian elphant. Like all herpesviruses, EEHV has a latent phase in a so far unknown tissue of the elephant body. For reasons that are not yet known, the virus can be reactivated, probably due to a (temporary) weakening of the elephant's immune system. The virus migrates to the mucous membranes of the mouth, trunk, eyes and the female genital tract. Shedding in semen or mucous membranes of the penis has not yet b een reported. Shedding has been observed in a zoo-kept herd of Asian elephants after the introduction of a bull and on a second occasion after the introduction of 2 females (Titus, 2022). In another zoo, 2 young Asian elephant calves died of EEHV1 within 2 weeks after the introduction of a breeding bull (Dublin zoo, 2024). Both calves appeared to have no antibodies against EEHV1a and EEHV1b. These findings suggest that the introduction of adult elephants in a herd can induce virus reactivation and consequently virus shedding. (Maternal) antibodies Humoral antibodies can be demonstrated by using recently developed antibody assays. A fluorescence based assay (Lips assay) has become available in the USA (Fuery, 2020) and an ELISA-based assay in the Netherlands (Hoornweg, 2021 ) . Serological studies using these assays demonstrated that maternal antibodies remain circulating for up to 36 months in elephant calves (Fuery, 2020). These maternal antibodies are transmitted in the uterus. The long period during which they are circulating at high levels in a young elephant, suggests that this species is able to absorb antibodies excreted by the dam in her milk. This is also suggested by Takehana et al 2024 , who described that the antibody level in a bottle-fed elephant calf decreased within 14 months as compared to 2 other calves in the same herd, in which antibodies remained high for more than 2 years. However, this hypothesis still needs to be proven. EEHV-subspecies and subtype-specificity has been demonstrated for these assays (Hoornweg, 2023 ) . Another finding was that antibodies against EEHV4 were not protective against fatal EEHV1a infections, while antibodies against EEHV1a seem to protect against illness caused by EEHV4 and EEHV5. Hoornweg et al. studied 23 fetal EEHV-HD cases in European zoos and found that all fatalities had low antibody levels against gH/gL of the EEHV (sub)species they succumbed to (Hoornweg, 2024) . During the first 12 months of life, maternal antibodies seem to remain stable at a high level, which seems to protect the calf from developing Hemorrhagic Disease when infected by EEHV. This may explain why clinical EEHV-cases have never been reported below the age of 1 year. This has lead to the hypothesis that young elephants need to be exposed to EEHV while they are still (partly) protected by maternal antibodies. Shedding of EEHV by herd mates is therefore essential for the calf to build up natural immunity. In an elephant that is permanently infected with EEHV, shedding takes place after reactivation of EEHV. In 2 elephant orphanages in Sri Lanka (31 and 93 elephants), all calves had high levels of EEHV-gB antibodies. These 2 institutions never lost a calf to EEHV-HD. This leads to the conclusion that the larger herd sized in these 2 orphanages (compared to zoos increases the likelihood of cantact between EEHV-shedders. Herpes viruses in general can become reactivated during a stressful situation, when the immune system of the host seems to become weaker, possibly under the influence of endogenous glucocorticosteroids. Specific stress inducers that result in EEHV-reactivation are not yet known for elephants. It is tempting to hypothesize that social stress could be one of those factors, as elephants are highly social animals. Zoos generally try to avoid stress situations for their animals, including elephants, especially when there is a young calf in the herd. In the light of the recent findings, the absence of stress might as well work against the development of acquired immunity against EEHV in young calves. The same hypothesis could be valid for elephants in wild situations: if social stress factors are absent in some of the wild situations (less contact with other herds due to habitat fragmentation, less contact with bulls in musth), reactivation frequency of EEHV may be reduced in (sub)adults, preventing calves younger than 12 months from building up immunity during the crucial time frame when they are still protected by maternal antibodies. Clinical signs and diagnosis: 10-14 days before the elephant shows clinical signs of EEHV-HD, the presence of the virus can be demonstrated in the blood by qPCR (EDTA blood sample). It is important to monitor the presence of EEHV in calves between 1 and 9 years of age on a weekly base. As soon as the presence of EEHV has been confirmed, the number of monocytes and platelets are indicative for the further development of the virus in the days to come. When monocytes and platelets are stable and the viral load remains below 5.000 Viral Genome Equivalents (VGE's)/ml, close observation is required. As soon as the viral load in the blood increases or monocytes or platelets drop, immediate treatment is required. If the initial viremia has passed unnoticed, the young elephant may display one or more of the following unspecific symptoms: lethargy, reduced appetite, lameness, abnormal sleeping pattern, soft feces. In more advanced cases petechiae are seen on the tongue, edema on the head and front legs and finally cyanosis (purple tongue). Sometimes the severe symptoms are the first ones to be discovered. Photo: courtesy of Florence Ollivet-Courtois The most relevant tools needed for the diagnosis of EEHV-HD are: qPCR and total WBC, platelet count and blood smear (manual count of monocyte and heterophyls). The monocyte/heterophil (M/H) ratio is an important prognostic indicator for EEHV-HD. A ratio below 1 is reason for great concern and immediate treatment should be started. Blood smears are essential for manual differentiation of the white blood cells and recognition of the morphology. Note that the presence band-heterophils in young elephants is a bad sign! Lactate is an important serum parameter to monitor in a EEHV-HD case. Normal values are between 0--0.11 mmol/L (0-1 mg/dL). Values >0.44 mmol/L (4 mg/dL) are indicative for perfusion problems due to DIC (see below). EEHV-HD patients often have lactate value > 0.22 mmol/L (2 mg/dL) (Wiedner, pers. comm. 2022). Reports from Thailand suggest that a (primary?) infection with EEHV4 is generally associated with intestinal problems (Kittisirikul, 2025). At rectal examination, edema of the rectal mucosa can be diagnosed. This finding is supported by histopathological findings in fatal EEHV-HD cases ( Sripiboon, 2013) . Disseminated Intravascular Coagulopathy (DIC) One of the main reasons an EEHV infection can lead to severe illness or death is the development of DIC in young calves that are not adequately protected by (maternal) antibodies. DIC results from a severe, dysregulated immune response triggered when endothelial cells are damaged by the virus (endothelial glycocalyx degradation). Two independent studies have clearly demonstrated the occurrence of DIC in fatal cases of EEHV-HD (Guntawang, 2021; Perrin, 2021). In the treatment protocol for EEHV-HD, addressing DIC is a top priority. Cytokine Storm? In recent years, researchers have questioned whether a cytokine storm—described in human hemorrhagic fevers such as Ebola and Dengue—also plays a role in the development of EEHV-related DIC in elephants. A recent study reported a significant increase in interleukin-6 (IL-6) and interleukin-10 (IL-10) levels in the tissues and blood of six elephants suffering from clinical EEHV1a-HD (Hoornweg, 2025). Moreover, 2 elephants with clinical EEHV1a-HD that were treated with glucocorticosteroids, had lower serum levels of IL6 and IL10 than those that were not treated and even lower than the assumed reference level. Both elephants survived the clinical EEHV-HD infection. Elevated levels of these two interleukins are commonly associated with cytokine storms, suggesting that this phenomenon may also occur in EEHV-HD. These findings support the theory that the administration of glucocorticosteroids are indicated in the early phase of the hemorrhagic disease. Photo: courtesy African Lion Safari Park Photo: courtesy Amersfoort Zoo Pathological findings at necropsy The most prominent signs of EEHV-HD at necropsy are those that resulted from DIC: cyanosis of the tongue, subcutaneous edema, hemorrhages in most of the organs, joints and muscles, ranging from petechiae to large hematomas. There may also be a hydro-or hemopericardium. Especially in the case of EEHV4, the cecum and colon can be congested, hemorrrhagic and containing abnormal watery dark-brown content. Hemorrhages in the heart, intestines, brain and liver of a yound elephant that died of EEHV1a-HD. Photos by Arun Zacharia Coinfection of EEHV-HD and Clostridium perfringens α, βand ε. One report describes a coinfection of EEHV4 and Clostridium perfringens in a 7-month-old Asian elephant bull calf (Boonsri et al., 2018). The animal died within 2 days after the onset of the first clinical signs. At necropsy, basophilic intranuclear inclusion bodies were identified in the endothelial cells of blood vessels in the heart, lungs, liver, and spleen. This finding is indicative of a primary EEHV4 infection, despite the calf being suckled by its mother. Under normal circumstances, maternally derived antibodies would be expected to confer partial protection; however, this protection may have been insufficient, possibly due to a lack of prior immunity in the dam. Alternatively, the concurrent C. perfringens infection may have predisposed the calf to viral disease by compromising mucosal barriers or inducing systemic stress, thereby reducing the effectiveness of existing maternal antibodies against the virulence of the virus. The same authors also describe a coinfection involving EEHV1a and C. perfringens in a 3-month-old, female, wild-born Asian elephant that died within 6 hours after the onset of clinical signs. Although samples from the heart, lungs, liver, and spleen tested positive for EEHV by polymerase chain reaction, no intranuclear inclusion bodies were observed upon histopathological examination. This discrepancy suggests that, in this case, maternally derived antibodies may have partially inhibited viral replication within endothelial cells, thereby preventing the formation of characteristic inclusion bodies. Nevertheless, the rapid clinical deterioration indicates that other pathogenic mechanisms, potentially including the effects of C. perfringens toxins, may have played a decisive role in the fatal outcome. Taken together, these cases highlight the potential for synergistic interactions between EEHV and C. perfringens infections. Such interactions may exacerbate disease severity through combined effects on vascular integrity, immune function, and systemic homeostasis. Click here for the EAZA elephant TAG EEHV treatment protocol Treatment of EEHV-HD Early treatment of EEHV-HD 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. Repetitive sedations have been given to sick calves without negative effects. If butorphanol is used to obtain sedation, it should not be antagonized as it will help to relieve the pain in the patient. Circulatory support: Rectal fluids: Luke-warm water 10-20 ml/kg BW TID or QID, up to every 2 hours NB: As repeated rectal fluid administrations may be needed, the anus of the elephant may become sensitive to these procedures. Rx: mix 15 ml lidocaine 2% with some lubricant and carefully apply on the anus. Wait for 10 minutes before placing the tube in the rectum for the administration of fluids. Repeated rectal exploration may be cause painful irritation of the anal sphincter and perianal skin. Adding lidocain to the lubricant may facilitate the exploration. Crystalloids: IV as a bolus of 0.3-4 ml/kg BW When blood or plasma is available, the administration of those products has preference over crystolloids. Whole blood transfusion: Indicated in case of anemia or severely delayed coagulation. The advantage of whole blood administration lays in the rapid availability: no waiting time for preparing plasma. A practical strategy is to collect sufficient blood from a donor elephant to make it available for whole blood (1-2 L) and save the rest to prepare it for plasma transfusions. Dosage whole blood transfusion: 1-2 L. Cross matching needs to be done prior to the transfusion. Plasma transfusion: IV bolus of 0.5-2 ml/kg BW (after minor cross matching of donor and recipient blood) For plasma transfusion in elephants see: Emergency care for elephants clinically ill from Elephant Endotheliotropic Herpes Virus–hemorrhagic disease (EEHV-HD, EAZA Elephant TAG, compiled by Fieke Molenaar (ZSL-Whipsnade zoo), Mads Bertelsen and Kathryn Perrin (Copenhagen zoo), Imke Lueders (GEOLifes), Lauren Howard (Houston zoo), Willem Schaftenaar (vet adv. EAZA Elephant TAG, 9 February 2021) Plasma is currently considered one of the best supportive therapies to provide, as platelets, clotting factors and potentially protective antibodies can thus be provided. Note that the freezing process activates platelets, which may render them useless at the time of transfusion. Therefore - where possible - freshly collected plasma is preferred. The following should be considered for plasma transfusions: If frozen plasma is available, this can be given in an early stage of the disease to save time (despite the activated and spent platelets). Blood collection from an adult elephant (plasma donor) should be initiated to provide fresh plasma as soon as possible. Cross-matching the donor animals with the recipients, especially if one donor will be used on multiple occasions. For more information about plasma transfusion: click here Anti-inflammatory treatment : Gluco-corticosteroid drugs are indicated in case of suspicion of DIC. Recent research could demonstrate an increase of interleukin 6 (IL6) and interleukin 10 (IL10) in tissues of elephants that succumbed to EEHV-HD and below-normal levels in blood of 2 survivors that were treated with glucocorticosteroids (Hoornweg, 2025). Dexamethasone: Used in 2 EEHV1a-HD survivor cases: Case 1: started with 0.2 mg/kg (200 mg) IV and continued daily for 12 days (final dose 0.007 mg/kg = 7 mg). Case 2: 2 mg/kg iv SID for 5 days, followed by 1 mg/kg iv SID for 2 days Triamcinolon : 0.067 mg/kg IV SID for 1-3 days (used in 1 EEHV1a-HD survivor case). Methylprednisolone sodium succinate: 0.5 mg/kg IV or IM; much higher doses are used for treatment of shock in horses: 10 - 20 mg/kg IV. Please note that in human medicine DIC (e.g. in Covid-19 cases) is treated with Dexamethasone 0.1mg/kg SID for 7-10 days ( https://www.who.int/news-room/q-a-detail/coronavirus-disease-covid-19-dexamethasone#:~:text=Recommendation%201%3AWHO%20strongly,medication%20for%20another%20condition .) Antiviral treatment: Several antiviral drugs are routinely used, although none of these have proven to be effective; preliminary studies are suggesting that the TK-gene of EEHV does not make the virus sensitive for the group of “ciclovirs” that is currently used. Famciclovir has been used most frequently, followed by ganciclovir. In the absence of the former antivirals, aciclovir has been given in several cases. Famciclovir: 15 mg/kg orally or rectally, TID Aciclovir: 15 mg/kg BID orally, rectally or IV (Ganciclovir: 5 mg/kg BW BID 5 mg/kg IV, BID, each dose given slowly diluted in 1 liter of NaCl. NB Ganciclovir is not preferred, as it is considered a potential human carcinogen, teratogen, and mutagen) Antibiotic treatment: A broad-spectrum antibiotic is recommended as the integrity of the intestinal wall may be disrupted and gut bacteria may leak into the abdominal cavity. Pain management: Pain management (opioids, NSAIDs) is recommended if there are clear signs of pain or discomfort Butorphanol (first choice): 0.008-0.014 mg/kg IM Q 4 hrs Flunixin: 0.25 to 0.5 mg/kg IM SID Omeprazole: 0.7 to 1.4 mg/kg PO SID Immunostimulating drugs: Immunostimulants have been used in one case of EEHV1a-HD: Interferon alpha 2a or 2b (25 mIU/2.5 ml Intron A, Merck or 4.5 mIU/0.5 ml Roferon A, Roche) were administered at 27–33 mIU intramuscularly once a day on days 1–12 then every 48 hours to day 20, administered by dart on days with no treatment session, incomplete delivery on days 8 and 14. Bacterial plasmid DNA in a liposome carrier (Zelnate DNA immunostimulant, Bayer HealthCare LLC) was given to the same elephant (2 ml intramuscularly on days 0, 4, 7 and 12). It should be noted that the same elephant was also given anti-inflammatory treatment (dexamethasone). WS personal note: It should also be noted that interferon levels are expected to be elevated in case of a cytokine storm. As there is no scientific proof of the benefits of interferon treatment in EEHV-HD, care must be taken to use any interferon-containing drug formulation! Adjunctive drugs: Oxygen should always be standby and administered as soon as signs of hypoxemia are seen. Furosemide (1 mg/kg IM ) has been given occasionally. Vitamin C, routine used in Asia (dos age depends on product; use equine dose). Vitamin E (dosage depends on product; use equine dose). Monitoring the course of the disease: The serum lactate level gives an indication of the organ perfusion. In EEHV-HD patients, the lactate level is often higher than 2 mmol/L (normal value: 0-1 mmol/L). Rehydration by the fluid administrations will help to decrease an elevated lactate. Platelet counts during the treatment course are helpfull in evaluating the success of the treatment. The administration of whole blood and plasma will compensate partly the loss of platelets and also provide antibodies if the donor is an adult elephant. It is advisable to make sure that the donor does have antibodies. Blood pressure : in severe EEHV-case, the blood pressure may decrease or decrease. Fluid administration may help to stabilize the blood pressure. When the patient has a vascular shock, the blood pressure may be low. A fast administered bolus of rectal fluids (0.5-5 ml/kg BW) within 15-30 minutes may help to increase the blood pressure. To standing sedation Treatment of EEHV-HD Cross-matching procedure Based on design elaborated by Houston Zoo, Inc. Step one: Prepare a 3-5% red cell suspension. 1. Collect blood from both donor and recipient in EDTA. 2. Centrifuge the tube and separate the plasma from the red cells. Save both. 3. Place 1 drop of recipient red cells into a small (2-5 ml) clean test tube. 4. Add approx. 1-2 ml of normal saline to the tube with the red cells (or 1 drop RBC to 40 drops saline) 5. Centrifuge at 2500 RPM for 20 seconds. 6. Remove the supernatant, leaving the red cell button on the bottom. 7. Repeat steps 4-6 three times (for a total of 4 washes). 8. Add 1 drop of newly washed recipient red cells to a new test tube. 9. Add approximately 20-40 drops of saline and mix to suspend the red cells. This should be an approximate 3-5% cell suspension to work with. Step two: Minor cross-match (for plasma transfusion). 1. Add 1 drop of the recipient’s 3-5% red cell suspension to a labeled test tube. Add 1 drop of the recipient’s 3-5% red cell suspension to another labeled test tube to be used as a control. 2. Add 2 drops of donor plasma or serum to the test tube. 3. Add 2 drops of saline to the control tube. 4. Incubate these tubes at 37oC for 15 minutes. 5. Centrifuge the tubes for 20 seconds at 2500 RPM. 6. Observe the supernatant for signs of haemolysis. If present in the cross-match tube and not the control tube, the match is not compatible. If present in both, start again with a new cell suspension. 7. If no haemolysis, then gently rock the test tube back and forth to re-suspend the cell button. Observe the cell button while rocking the tube and grade for the presence of agglutination. Grade on a 0-4 scale where 0 is no agglutination and 4 is heavy clumping. Record your results. Step three: Major cross-match (for whole blood transfusion). 1. Add 1 drop of the donor’s 3-5% red cell suspension to a labeled test tube. Add 1 drop of the donor’s 3-5% red cell suspension to another labeled test tube to be used as a control. 2. Add 2 drops of recipient’s plasma or serum to the test tube. 3. Add 2 drops of saline to the control tube. 4. Incubate these tubes at 35-37oC for 15 minutes. 5. Centrifuge the tubes for 20 seconds at 2500 RPM. 6. Observe the supernatant for signs of haemolysis. If present in the cross-match tube and not the control tube, the match is not compatible. If present in both, start again with a new cell suspension. 7. If no haemolysis, then gently rock the test tube back and forth to re-suspend the cell button. Observe the cell button while rocking the tube and grade for the presence of agglutination. Grade on a 0-4 scale where 0 is no agglutination and 4 is heavy clumping. Record your results. Anchor 1 References: Boonsri K, Somgird C, Noinafai P, Pringproa K, Janyamethakul T, Angkawanish T, Brown JL, Tankaew P, Srivorakul S, and Thitaram C. 2018. Elephant Endotheliotropic Herpervirsus associated with Clostridium perfringens infection in two Asiane elephants ( Elephas maximus ) calves. Journal of Zoo and Wildlife Medicine 49(1): 178–182, 2018 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. Guntawang T, Sittisak T, Kochagul V. ,Srivorakul S., Photichai K., Boonsri K., Janyamethakul T., Boonprasert K., Langkaphin W.5, Chatchote Thitaram C. and Pringproa K. 2021. Pathogenesis of hemorrhagic disease caused by elephant endotheliotropic herpesvirus (EEHV) in Asian elephants (Elephas maximus ). Scientific Reports (2021). 11:12998. https://doi.org/10.1038/s41598-021-92393-8 Hoornweg TE, Schaftenaar W, Maurer G, van der Doel PB, Molenaar F, Chamour-Galante A, Vercammen F, Rutten V and de Haan CAM. 2021. Elephant Endotheliotropic Herpes Virus is omnipresent in elephants in European zoos and an Asian elephant range country. Viruses 2021, 13, 283. https://doi.org/10.3390/v13020283. Hoornweg TE, Perere VP, Karunarathne NS, Schaftenaar W, Mahakapuge AN, Kalupahana AN, Rutten VPMG, de Haan CAM. 2022 . Young elephants in a large herd maintain high levels of elephant endotheliotropic herpesvirus-specific antibodies and do not succumb to fatal haemorrhagic disease. Transboundery and Emerging Diseases 69-5 . https://doi.org/10.1111/tbed.14644. Hoornweg TE, Schaftenaar W, Rutten VPMG, de Haan CAM. 2024. Low gH/gL (Sub)Species-Specific Antibody Levels Indicate Elephants at Risk of Fatal Elephant Endotheliotropic Herpesvirus Hemorrhagic Disease. Viruses. 2024; 16(2):268. https://doi.org/10.3390/v16020268. Hoornweg TE, Schaftenaar W, IJzer J, Mulder MMP, Lugtenburg M, van Beest A, de Haan CAM and Rutten VPMG (2025) Elevated IL-6, IL-10, and IFN-g levels in fatal elephant endotheliotropic herpesvirus – hemorrhagic disease cases suggest an excessive proinflammatory cytokine response contributes to pathogenesis. Front. Immunol. 16:1645752. doi: 10.3389/fimmu.2025.1645752 Howard L.L. & Schaftenaar W. 2017. Elephant Endotheliotropic Herpes Virus. In: Fowler’s Zoo and Wild Animal Medicine Current Therapy, Volume 9. Kittisirikul N, Angkawanish T, Langkaphin W, Chaopong O, Thaitam B and Sripiboon S. 2025 Challenging management of clinical EEHV4 infection in an adult Asian elephant. 21st International Elephant Conservation and Research Symposium. Fort Worth IEF, December 5-8. Luz S & Howard L.L. 2017. Elephant Endotheliotropic Herpesvirus (EEHV) in Asia. Recommendations from the 1st Asian EEHV Strategy Meeting (On behalf of the Asian EEHV Working Group), second edition. Perrin KL, Kristensen AT, Bertelsen MF, Denk D. 2021. Retrospective review of 27 European cases of fatal elephant endotheliotropic herpesvirus‑haemorrhagic disease reveals evidence of disseminated intravascular coagulation. Scientific Reports (2021) 11:14173, https://doi.org/10.1038/s41598-021-93478-0. Sripiboon S, Tankaew P, Lungka G and Thitaram C. 2013. The occurrence of Elephant Endotheliotropic Herpes Virus in captive Asian elephants (Elephas maximus ): first case of EEHV4 in Asia. Journal of Zoo and Wildlife Medicine 44(1): 100–104, 2013. Takehana K, Hoornweg TE, Schaftenaar W), Rutten VPMG, de Haan CAM, Matsuno K. 2024. Elephant endotheliotropic herpesvirus gB-specific antibody levels in sera of Asian elephants (Elephas maximus) in Japanese zoos. J Vet Med Sci 86(12): 1279–1283, 2024 doi: 10.1292/jvms.23-0503. Titus SE, Patterson S, Prince-Wright J, Dastjerdi A, Molenaar FM. 2022. Effects of between and within Herd Moves on Elephant Endotheliotropic Herpesvirus (EEHV) Recrudescence and Shedding in Captive Asian Elephants (Elephas maximus ). Viruses, 14(2) 2022. doi:10.3390/v14020229. Wissink N. et al. 2018. Using in-house hematology to direct decisionmaking in the successful treatment and monitoring of a clinical and subsequently subclinical case of Elephant Endotheliotropic Her Vitus 1B. J. of Zoo and Wildlife Med., 50(2): 498-502 For more information see: http://eehvinfo.org/ To page top

The dermatology-page will direct you to the chapters about skin wounds, skin abscesses, skin infections, tempral gland infection and temporal gland surgery. To case report index Dermatology Skin wounds Abscesses (needs your input) Skin infections (needs your input) Cutaneous filariasis Vaginal vestibulotomy Temporal gland impaction Temporal gland impaction/surgery

An adult Asian elephant suffered form a severe infection of Salmonellosis (S. saintpaul). It went down and was unresponsive. Hematology and treatment results are discussed. To Salmonellosis Next case Next case Case Report Next case Salomonella saintpaul septicemia in an adult Asian elephant Next case Date: 2021 Location: Italy (zoo) Submitted by: Fieke Molenaar DVM and Pasqualino Silvestre DVM History Three months after the move to another zoo, a 37 year-old female Asian elephant (Elephas maximus) presented mild lethargy and a reduction of food and water intake. Mild colics were suspected and the elephant was treated with non-steroidal anti-inflammatories (NSAID, meloxicam i.m. ~ 0.2 mg/kg) and spasmolytics (metamizole and butylscopolamine bromide i.m., ~ 80 and 5mg/kg). As no improvement was noticed on Day 2, a standing sedation was carried out (detomidine i.m., ~ 0.018 mg/kg, and butorphanol (i.m., ~ 0.017 mg/kg). Rectal fluids (20 L of hand-warm tap water) and i.v. fluids (4 L of 0.9% saline solution) were administered, as well as i.m. injections with amoxicillin (~ 15 mg/kg), vitamin B-complex and vitamin E/selenium. Flunixin meglumine was given in the auricular vein. Sedation was reversed using atipamezole (i.m., ~ 0.05 mg/kg). Blood was collected during this procedure. Unfortunately, the elephant collapsed 9 hours later in lateral recumbency. The animal was unresponsive and could be approached while it kept its eyes wide open (see videos). The araol mucosa was very pale. After 25 minutes it managed to stand up without any assistance but remained lethargic. Respiration was shallow. During the night the elephant went down in lateral recumbency again. During the following 5 days, the elephant was sedated every day for treatment and blood collection. Next case Collapsed Asian elephant due to septicemia caused by Salmonella saintpaul . Note the pale oral mucosa. The state of paralysis very much looks like the paralysis seen in botulism ( see case report ). Laboratory results: Hematology: Leucopenia was evident on the first blood smear that was made, with a clear increase of bands and a reduction of matured heterophils. An interesting finding was the presence of immature granulocytes (myelocytes) that could not be identified exactly. The platelet count was low and schistocytes (fragments of erythrocytes) were observed in each view. The presence of schistocytes is suggestive for the presences of a coagulopathy. In conclusion: based on the hemogram, a diffuse intravascular coagulopathy (DIC) was suspected, most likely associated with septicemia caused by a bacterial infection or a toxicosis. Interestingly, EEHV 3/4 was detected by a combined PCR test for subtype 3 and 4 in a blood sample and in trunk swabs. The elephant had been tested PCR positive for EEHV4 previously. A trunk swab taken from the conspecific that shared the enclosure was PCR-negative. For photos of elephant heterophils, bands, platelets and schitsocytes: click here . Human myelocyte, containing both primary (azurophilic) and secondary/specific (pink or lilac) cytoplasmic granules. The proportion of secondary granules increases as the cell matures. The nucleus is round and lacks a nucleolus. Courtesy: ASH Image Bank Myelocyte of the Asian elephant in this case report. The quality of this photo is poor as it was taken with a cell-phone through the ocular lens of the microscope. Urinalysis: Daily urine samples were taken and analyzed using a dipstick and refractometer from Day 3 onwards. Initially a high specific gravity with a low pH was determined, suggestive for severe dehydration and metabolic acidosis. Fecal culture and treatment: A fecal sample collected on Day 3 was submitted for bacteriology. The treatment plan focused on the suspected septicemia. Treatment with NSAID was continued and the antimicrobial treatment was switched to enrofloxacin (per rectum, ~ 2.5 mg/kg) and metronidazole (per rectum, ~ 11 mg/kg). Administration of vitamin B-complex and E/selenium was repeated on day 4 and day 5. Preventive measures In an attempt to find the causative agent of the suspected septicemia, stored hay was inspected for mould and other conditions that favor (an)aerobic growth of toxin producing bacteria, more specifically Clostridium spp. All sand in the enclosure was replaced; drains and surfaces were disinfected with 5% sodium hypochlorite before new sand was brought in. Treatment (continuation) On Day 9 Salmonella saintpaul sensitive for enrofloxacin was isolated from the feces. Until Day 6, dehydration was getting worse, based on hematological findings (increased Ht) and urinalysis (increased specific gravity). On Day 7 no feces were produced (probably caused by the anorexia and repeated administration of detomidine) and diphteric necrotic tissue was observed during the administration of rectal fluids. In the mean time, hematology results started to show evidence of recovery from the septicemia: bands had dropped from 36% (Day 5) to 11%, while platelets increased from 320 (Day 2) to 437 x109/L. WBCs increased from 3.3 (Day3) to 10.5 x 106/L. Interestingly, the number of myelocytes increased to 35% on Day 7, but sharply dropped to 5% on Day 8 and they totally disappeared after that day. All hematological parameters were normal when checked again on Day 48 and 55. In order to stimulate the appetite and the intake of fibrous food, daily sedations were discontinued as from Day 8, and the focus of treatment moved to provide gastro-protection and stimulation of the duodenal motility by the administration of ranitidine (oral, ~ 0.25 mg/kg) twice daily. Water soaked bran and hay ad lib, bamboo browse and banana tree-trunks were offered as much as possible. Sugar-containing food items were restricted to treats for compliance to vocal commands by the keepers in order to get cooperation from the elephant for the necessary treatment procedures. The animal regained its strength and body condition over the 3 month-period following this clinical episode. The presence of EEHV3/4 in the blood and trunk swab can be explained by a virus reactivation due to the sudden deficiency of the immune system as a result of the septicemia and DIC. No clinical impact is to be expected from this finding, as the animal known to be a carrier of EEHV4. References Molenaar, F.M. and Silvestre S. 2021. Clinical approach to colic and collapse in an Asian elephant ( Elephas maximus ) with Salmonella saintpaul septicaemia and subsequent ileus. Vet Rec Case Rep. 2021;e214. https://doi.org/10.1002/vrc2.214 . To page top

Rabies has been diagnosed in a few elephants and was fatal in all reported cases. The source of the infection was attributed to canids (Wimalaratne et al. 1999, Nanayakkara et al. 2003, Sharma et al. 2005, Aravind et al. 2006). The incubation time for rabies in elephants is unknown. Depending on the distance between the bite wound and the elephant's brain, a long incubation period can be expected. Rabies should be included in the differential diagnosis whenever there are neurological signs. To infectious diseases Rabies General information Rabies is a viral disease that is usually fatal. It is caused by a neurotropic Lyssa virus. Several species of Lyssaviruses have been identified, of which the rabies virus (worldwide), the Mokola virus (Africa), the Duvenhage virus (South Africa) and the European and Australian bat lyssaviruses are responsible for fatal encephalomyelitis. Rabies is transmitted by a percutaneous bite from a rabies-infected animal or by wound contamination with saliva from a rabid animal (MSD, 2021). Air born infection through aerosols can occur when visiting bat caves. Reservoir hosts vary geographically. In the U.S. hosts include skunks, bats, raccoons, foxes, and coyotes. Civets, mongooses and hyenas are the main hosts in Africa; domestic dogs are hosts in Asia, South America, and Africa. Certain bat species in southern Africa are host for a Lyssa virus After infection of the bite wound, the virus migrates from the wound to the brain via the nerves that run from the wound area, resulting in neurological signs. Virus replication takes place in the brain, from where the virus migrates to the salivary glands. The incubation period varies from 3 weeks to many months. In most species affected by rabies, the animal shows an increase of aggressive behaviour and will try to bite other animals. Hydrophobia can be one of the accompanying symptoms. In a few species (e.g. domestic cat), the animal becomes more quite or even soporous. Once the virus has reached the brain, there is no cure. Treatment is only possible in the short period between infection and start of the migration. In this short time window, the animal should be treated daily with a rabies vaccine (described below). If available, locally anti-rabies serum should be injected around the wound area. Diagnose of rabies is based on PCR or histopathology of brain tissue by demonstrating the presence of typical Negri bodies using a special stain especially in pyramidal cells within the Ammon's horn of the hippocampus. Wound tissue, saliva and cerebrospinal fluid can be used when the animal is still alive (CDC, 2021). Rabies in elephants Rabies has been diagnosed in a few elephants and was fatal in all reported cases. The source of the infection was attributed to canids ( Wimalaratne et al. 1999, Nanayakkara et al. 2003, Sharma et al. 2005, Aravind et al. 2006). The incubation time for rabies in elephants is unknown. Depending on the distance between the bite wound and the elephant's brain, a long incubation period can be expected. Rabies should be included in the differential diagnosis whenever there are neurological signs. The initial signs of rabies in elephants may be vague but most often the elephant (FAO 2005): Is listless. Prefers to stay in dark places. Eats very little. As the disease progresses the elephant likely: Writhes in pain. Does not recognize the mahout. Chases and attacks humans and animals. Has eyes that roll and wander. Does not eat. Walks unsteadily and the legs lose strength. Goes to the ground in paralysis. Has locked jaws and the tail hangs still. Has saliva flowing continuously. Death may shortly follow the appearance of these more severe signs. The differential diagnose in case of rabies comprises any disease that can cause central nervous system symptoms, like: Tetanus Trauma Snakebite Toxicity (e.g. heavy metal; pesticide) Anytime an elephant is bitten, particularly if the bite has drawn blood, the mahout and owner should take four actions: 1. Write the day on a calendar; then you will be able to predict when the elephant may show clinical signs if it was infected. 2. Talk to people who know the dog and ask about its behaviour in the days prior to the attack; if the dog has been acting strangely (staring fixedly, foaming at the mouth, etc.) there is a good chance the dog is rabid. 3. Inform everybody in the community of the health hazard, because the disease also attacks humans, and ask them to help track down the dog. 4. Very carefully capture the dog, confine it securely, and observe its condition; if after ten days it is normal then the elephant does not have rabies. If the elephant dies, consult Disposal of carcasses, page 55 of the FAO manual . Treatment of rabies in elephants Immediately after a suspected dog bite, wash the wound intensively with soap and water. Then apply tincture of iodine or Povidone-iodine 1% in and around the wound (FAO 2005). There is no effective treatment once the symptoms have appeared. Even though the disease is not contagious to other elephants, separate the elephant, taking it to a shady, clean and quiet place. Make sure the elephant is chained tightly and securely (FAO 2005). Although there is no report on post-exposure vaccination, emergency vaccination of the elephant can be considered, if a rabies vaccine is available. One study describes the successful post-exposure treatment in pigs that where heavily exposed to rabies. The affected pigs were repeatedly vaccinated with an inactivated rabies vaccine 0, 3, 7, 14 and 30 days after the bite incident, while equine rabies immune globulins were injected in and around the bite wound (Mitmoonpitak et al. 2002). When an elephant is exposed to rabies, consider to inject the animal intramuscularly with a 2 ml dose of an (inactivated = killed) rabies vaccine as soon as possible after it was bitten by a rabid animal. These vaccinations should to be given daily for at least 5 days. During this period the elephant should be kept under close observation. Anytime an elephant is bitten, particularly if the bite has drawn blood, the mahout and owner should take four actions: Write the day on a calendar; then you will be able to predict when the elephant may show clinical signs if it was infected. Talk to people who know the dog and ask about its behaviour in the days prior to the attack; if the dog has been acting strangely (staring fixedly, foaming at the mouth, etc.) there is a good chance the dog is rabid. Inform everybody in the community of the health hazard, because the disease also attacks humans, and ask them to help track down the dog. Very carefully capture the dog, confine it securely, and observe its condition; if after ten days it is normal then the elephant does not have rabies. If the elephant dies, consult Disposal of carcasses, page 55 of the FAO manual . Prevention Regular rabies vaccination is recommended for all elephants kept under human care in areas where rabies is endemic. Because rabies is incurable the best prevention is to annually vaccinate all the dogs and cats in the community. 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. See also: vaccination. References Aravind B., Anilkumar M., Raju S., and Saseendranath M.R. 2006. A case of rabies in an Indian elephant (Elephas maximus) . Zoo's print journal 21 (2) 2170. 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. CDC 2021: https://www.cdc.gov/rabies/diagnosis/animals-humans.html FAO 2005: Elephant care manual for mahouts and camp managers. 2005. Isaza R., Davis R.D., Moore S.M., and Briggs D.J. 2006. Results of vaccinat i on of Asian elephants (Elephas maximus) with monovalent inactivated rabies vaccine. AJVR, Vol 67 (11), 1934-1936, 2006 Miller M.A. and Olea-Popelka F. 2009. Serum antibody titers following routine rabies vaccination in African elephants. JAVMA, Vol 235 (8),978-981 2009 Mitmoonpitak C., Limusanno S., Khawplod P., Tepsumethanon V, and Wilde H. 2002. Post-exposure rabies treatment in pigs. Vaccine 20 (2002) 2019–2021. MSD, 2021: https://www.msdmanuals.com/home/brain,-spinal-cord,-and-nerve-disorders/brain-infections/rabies Nanayakkara S, Jean S. Smith, and Charles E. Rupprecht. 2003. Rabies in Sri Lanka: Splendid Isolation. Emerging Infectious Diseases • Vol. 9, No. 3, March 2003. Sharma A.K., Choudhury B, and Singh K.P. 2005. Rabies in a captive elephant . Indian Journal of Veterinary Pathology 29(2): 125-126 Wimalaratne O, and Kodikara D.S. 1999. First reported case of elephant rabies in Sri Lanka. Vet. Rec. 144 (4): 98. To page top