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 chapter describes cases reports submitted by veterinarians worldwide. Case reports Dentistry Back to Top Tusk fracture in 36 months old African elephant Tusk fracture repair in 9 yr-old Asian elephant Tusk fracture repair in 4 yr-old African elephant Tusk (crack) fissure repair in 22 yr-old Asian elephant Tusk sulcus infection in adult Asian elephant T usk sulcus trauma after tusk fracture (2x) Tush loss in female Asian elephant Mandibular fracture Weight loss due to abnormal molar change Supernumerary tusk in an African elephant Dermatology Skin wounds in adult Asian elephant Wound treatment after fetotomy Wound treatment after vaginal vestibulotomy Temporal gland impaction: non-surgical treatment Temporal gland impaction: surgical treatment Back to Top Reproduction Vaginal vestibulotomy (1996) Vaginal vestibulotomy (2014) Fetotomy Back to Top Ophthalmology Bilateral corneal opacity Back to Top Orthopedic problems Partial pad and nail loss in a 54 yrs-old female Asian elephant Back to Top Infectious diseases Salmonellosis in a group of African elephants Salmonellosis in 7 yr-old Asian elephant Colic and Salmonellosis in an adult Asian elephant Salmonella septicemia in an adult Asian elephant Elephant Endotheliotropic Herpes Virus-Hemorrhagic Disease (EEHV-HD) Fasciolasis in a group of African elephants Rabies in an Asian elephant Back to Top Non-infectious diseases Clostridium botulinum in a herd of elephants Back to Top Clostridium perfringens enterotoxemia in a 6 weeks-old African elephant Intoxication Dieffenbacchia intoxication Paraquat intoxication Back to Top Gastro-intestinal problems Esophagus spasm in an adult Asian elephant Esophagus impaction in a 4.5-yrs-old African elephant Hernia mesenterialis and intestinal rupture in an Asian elephant calf (1 year old) Intestinal impaction caused by Saccharum bengalense in a captive juvenile Asian Elephant: Implications for captive management. Back to Top Miscellaneous Hiccup Asian elephant with suspected hypocalcemia Hiccup Asian elephant with polycystic nephritis Perineal hernia Colic and abdominal surgery Allonursing in an African elephant Back to Top

ElephantMedicine.info provides information about infectious and non-infectious diseases in elephants, case reports, clinical and laboratory procedures and management guidelines. -Elephant Medicine -Diseases -Treatment -Anesthesia -Dental problems -Tusk repair -Laboratory tests - Hematology -elephant disease treatment -dental problems -locomotion -diagnostic procedures -physical examination -laboratory procedures -reproduction and birth procedures -anesthesia procedure -lameness -pedicure Elephant Medicine Get started A website for veterinarians taking care of elephants Sharing your clinical experience in ELEPHANT MEDICINE with elephant clinicians worldwide This website provides information about elephant diseases, procedures and recommendations. It also includes a collection of clinical case reports, submitted by veterinarians from all over the world. You will find cases that have been successfully treated, but also cases that had a sad ending. Some basic disease information is provided as well as descriptions of clinical and laboratory procedures. The information on this website is subject to changes, as our knowledge about diseases in elephants will grow by sharing our experiences. Veterinarians involved in elephant medicine are encouraged to submit reports of their experiences. Together we can create a platform for the current and next generations of veterinarians. For the benefit of an amazing, but vulnerable species: the elephant. Disclaimer: The content of this website, such as graphics, images, text and all other materials, is provided for reference and educational purposes only. The content is not meant to be complete or exhaustive or to be applicable to any specific individual's medical condition. The information is based on scientific literature, open source information and anecdotal information provided by trusted sources. You assume full responsibility for using the information on this site, and you understand and agree that the authors are not responsible or liable for any claim, loss or damage resulting from its use by you or any user. Contact

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: hemorrhages in most of the organs, joints and muscles, ranging from petechiae to large hematomas. There may also be a hydro-or hemopericardium. Hemorrhages in the heart, intestines, brain and liver of a yound elephant that died of EEHV1a-HD. Photos by Arun Zacharia 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: 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

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Leptospirosis in elephants has been described in Asian elephants. This page describes clinical cases and treatment as well as serological evidence of leptospirosis in apparently healthy elephants and the presence of leptospiresin elephant urine. Leptospirosis General information Leptospirosis is a bacterial infection caused by Leptospira spp . It is a common disease in many species of domestic animals. Leptospirosis is zoonotic. The bacteria are dispersed by urine of rodents, especially rats. The organism can survive many weeks in a slightly alkaline moist environment. The route of infection is by percutaneous inoculation of wounds or through mucous membranes. Several serovars have been associated with disease. Usually the liver is the target organ of Leptospira sp . Icterus, anemia, weight loss, (ventral) edema and general malaise are the main clinical signs. Ocular involvement (uveitis and hypopyon) may also occur. In elephants only a few clinical cases of leptospirosis have been reported. In one study in Sri Lanka, urine samples from 13 healthy domesticated elephants were collected on three consecutive days and analyzed for leptospiral DNA (Athapattu, 2019). Four elephants (31%) were confirmed to shed pathogenic leptospires in their urine. DNA sequencing followed by phylogenetic distance measurements revealed that all positive elephants were infected with L. interrogans. This study reveals the possibility that elephants may act as a source of infection for humans and recommends that all domesticated elephants that are in close contact with humans be screened to detect leptospiral shedding. In a study in India, serum samples were collected from 51 captive elephants kept in three different forest ranges (Shivraj, 2009). The samples were subjected to screening for leptospirosis using the microscopic agglutination test (MAT). It was found that out of the 51 samples seven elephant sera (13.72%) showed antibody titers against two serovars of Leptospira interrogans (L. australis and L. canicola) by MAT indicating the presence of infection or due to the past exposure of captive elephants to leptospiral antigens. In Thailand serum from 113 Asian elephants residing in 10 different tourist camps were tested using the microscopic agglutination test against 22 serovars of Leptospira interrogans (Oni, 2007). A seroprevalence of 58 % was found. The prevalent serovars were L. interrogans Sejroe, L. interrogans Tarassovi, L. interrogans Ranarum and L. interrogans Bataviae and L. interrogans Shermani . These results were similar to studies in domestic livestock and stray dogs in the Bangkok district. Because of the potential risk of indirect transmission of Leptospira spp from elephants to humans, 24 environmental samples were collected from an elephant camp area in western Thailand (Chaiwattanarungruengpaisan, 2019). Eighteen samples (75%) were culture-positive for Leptospira spp . The recovered leptospires were mostly derived from water and soil samples from a river and a mud pond, the main areas for recreational activities. The majority of the isolates were classified into the “Pathogens” clade (89%, 16/18) and more than half of the isolates (61%, 11/18) contained species of the “Saprophytes” clade. Notably, two soil isolates from the river beach sampling area were found to contain leptospiral DNA with high similarity to the pathogenic L. interrogans and L. santarosai . The evidence of diverse Leptospira spp ., particularly those belonging to the “Pathogens” clade, suggest that the shared environments of an elephant camp can serve as potential infection sources and may pose a risk to the elephant camp tourists and workers. It was not clear from this study whether the elephants were the source of these Leptospira spp. Leptospirosis in elephants One clinical case described the following clinical signs: chronic weight loss (400 kg) over a 4-month period (Fowler, 2006). Anorexia was profound. Leptospirosis was included in the differential diagnosis when the elephant developed uve itis and hypopyon . Titers for multiple serovars of Leptospira reached 1:12,800. The liver was the organ system infected. Icterus was marked. The sclera and hypopyon were both bright yellow. Total bilirubin reached 160 μmol/L (9.4 mg/dl), and liver enzymes were elevated. Ventral edema became pronounced, accompanied by ulcerating lesions of the vulva and various areas of the skin. The tip of the tail necrosed from vasculitis. Blood urea nitrogen and creatinine levels remained normal throughout the course of the disease, indicating that the urinary tract was not involved. Diagnosis was based on elevated titers for Leptospira serovars plus hypopyon and uveitis. The organism was not isolated nor could antigens be detected by PCR. Two other elephants cohabitating with the ill elephant developed low titers (1:200–400) for Leptospira icterohemorrhagica , but they did not develop clinical disease. Another case was described by Govindarjan (2006): A 16 yr-old Asian elephant bull was off food for one week. He developed icteric mucous membranes and his urine stained yellow (the author of this report did not mention the color in comparison with the color of normal urine, which is yellow as well). An 8-fold increase of antibodies against L. pyrogenes was observed within a 20-day interval. Diagnosis of leptospirosis is based on serological assays (Micro Agglutination Test MAT, ELISA), PCR, dark field microscopy, and silver impregnation staining. Treatment of elephants with clinical leptospirosis consists of the administration of antibiotics (tetracycline, doxycycline). In the case described above by Govindarjan, amoxicillin was given at a dose of 30 g/day IV for 14 days. References Fowler M. 2006. Infectious diseases. In: Biology, Medicine and Surgery of Elephants, Ed. Fowler and Mikota, 2006, 148. O. Oni, K. Sujit, S. Kasemsuwan, T. Sakpuaram, D. U. Pfeiffer. 2007. Seroprevalence of leptospirosis in domesticated Asian elephants (Elephas maximus) in north and west Thailand in 2004 Veterinary Record (2007) 160, 368-371. Sjivraj, M.D. Venkatesha, Sanjeevkumar, B.M.Chandranaik, Rajkumari Sanjukta, P.Giridhar, and C. Renukaprasad (2009). Detection of leptospiral antibodies in thesera of captive elephants. Veterinary World, Vol.2(4): 2009, 133-134. T. P. J. Athapattu, B. R. Fernando, N. Koizumi and C. D.Gamage. 2019. Detection of pathogenic leptospires in the urine of domesticated elephants in Sri Lanka. Acta Tropica Vol. 195 Pages 78-82 Chaiwattanarungruengpaisan, S., Thepapichaikul, W., Paungpin, W., Ketchim, K., Suwanpakdee, S., Thongdee, M., 2020. Potentially Pathogenic Leptospira in the Environment of an Elephant Camp in Thailand. Tropical Medicine and Infectious Disease 5, 183.. doi:10.3390/tropicalmed5040183 Leptospirosis AAZV fact sheet (2018) Leptospirosis EAZWV fact sheet (2003) To infectious diseases

A fractured elephant tusk can cause traumatic lesions of the tusk sulcus when the fracture site is located proximal to the sulcus. To tusk fracture Case report Tusk fracture and sulcus trauma (Asian elephant) Place: Planckendael Zoo Date: 2016 Data provided by: Francis Vercammen DVM History 6 yrs-old female Asian elephant with mucosal damage due to the sharp edges of the distal part of a fractured tush. Note the swollen sulcus mucosa. The pulp tissue was not exposed Treatment As the pulp tissue was not exposed, treatment was limited to grinding sharp edges away using a round-topped milling cutter on a hand-held drill (Dremel). The sulcus was flushed 3 times per day with a mild antiseptic solution (Iso-Betadine Gynecology) Treatment results The sulcus healed and the tusk continued to grow. Tusk fracture and sulcus trauma (Asian elephant) Date: 2020 History A 30 mo-old Asian elephant kept in a zoo fractured its right tusk. The pulp cavity was not exposed, but the sharp edges of the tusk remnant caused wounds on the sulcus mucosa. The sharp edges of the fractured tusk are often the cause trauma to the sulcus mucosa, resulting in a prulent infection. The sharp edges of the fractured tusk have caused a purulent infection of the sulcus. Treatment A conservative treatment was elected, consisting of flushing the wound several times per day with a saline solution and a 10% Betadine solution. Treatment result Within 3 months the tusk had grown out of the sulcus again and the wounds had healed completely. To page top

Tusk fractures should be treated as soon as possible. Both conservative treatment and surgical treatment, using a threaded rod and dental filling materials are described. Step by step you are guided through the entire procedure. To tusk fracture By Willem Schaftenaar (DVM) with a big thank you to the dental team of the Colyer Institute in San Diego: Jim Oosterhuis (DVM), Dave Fagan (dentist, and founder of Colyer Institute), Jeff Zuba (DVM, elephant anesthesiologist ), Allison Woody ( board certified veterinary dentist), Fred Pike (DVM, board certified veterinary surgeon) Tusk fracture repair Tusk fractures are not uncommon in elephants, both in the wild as well as under captive conditions. A tusk fracture can be the result of fights, playing with "toys" (e.g. a tire hanging on a chain), digging in the soil or hitting a wall or other heavy objects (e.g. bulls into musth). Fractured tushes in female Asian elephants usually need no treatment, as the dental pulp does not pass the tusk sulcus. However, fractures in tusks are vulnerable for pulp exposure. If not treated in due time, exposed pulp may become infected and become necrotic, finally resulting in the loss of the entire tusk. Cutting the tusk too short may also result in pulp exposure. Sulcus infection after tush fracture If a tush or tusk fractured proximal to the tush sulcus, sharp pieces of the remaining part of the tush or tusk may cause wounds in the sulcus. Treatment consists of removing these sharp edges of the tusk by rasping them off. The sulcus wounds should be treated like a superficial skin wound by daily cleaning and flushing with Ringer's lactate and an antiseptic (e.g. Betadine-iodine or Chlorhexidine 1%). WARNING: if the pulp tissue is exposed, the elephant should be vaccinated against tetanus! Pulp exposure and tusk growth Exposure of the pulp tissue always results in a bacterial pulpitis. As long as sufficient healthy pulp tissue is present in the apex of the tusk, the tusk may continue to grow. However, if the pulpitis is not treated properly, the infection will finally affect the entire pulp and the tusk will become necrotic and will need to be extracted. Treatment of open tusk fractures There are 2 approaches that are being applied as treatment of a fractured tusk: A. Conservative treatment B. Surgically filling the pulp canal A. Conservative treatment of fractures with minimal pulp exposure: daily cleaning and flushing with Ringer's lactate and an antiseptic (e.g. Betadine-iodine or Chlorhexidine 1%). This is not the preferred treatment option as it will often result in a permanent fistula, as shown here on the photo (small black spot). Nevertheless, the pulp canal was closed by newly formed secondary ivory. Conservative treatment of a tusk fracture with exposed pulp tissue, treated conservatively. The pulp canal closed in 3 months, leaving a very small fistula, which luckily that did not cause any clinical troubles during the following (6+) years. B. Surgically filling of the pulp canal The difference with a conservative treatment approach is the active closing of the pulp canal by a dental surgical procedure. This procedure consists of a partial pulpectomy, followed by closure of the pulp canal and will be described below: Tusk repair procedure Until the actual repair procedure will take place, any free hanging pulp tissue should be cut off and the exposed pulp tissue should be cleaned and flushed 3-4 times per day with saline solution. End each session by spraying Betadine solution or Chlorhexidine 1% over the pulp tissue. Antibiotics are usually not required as the wound is open and under control by flushing. However, the elephant should be vaccinated against tetanus. NSAIDs are only needed if the elephant shows signs of pain. The tusk repair procedure should be performed as soon as possible after the tusk fractured. Tusk repair procdure Fractures that are more or less perpendicular to the tusk length axis have better chances to heal than oblique fractures that extend beyond the sulcus. The best chances to heal properly are fractures with a tusk remnant that allows perpendicular shortening through healthy pulp tissue. In the photo shown here the following structures can be distinguished: exposed pulp tissue, the wall of the tusk remnant and the sulcus mucosa. If the remaining pulp tissue is hanging outside the tusk remnant immediately after the fracture, it is very likely that the proximal part of the remaining pulp tissue has detached from the inner tusk wall, which will result in pulp necrosis if not treated immediately after the tusk fractured. If sufficient pulp tissue can be removed to reach healthy tissue, the prognosis of complete healing is better than in case the pulp tissue encountered after pulpectomy is still detached from the inner tusk wall. Pulp tissue that is hanging outside the pulp canal should be cut off as soon as possible. Preparation –Check the equipment list –Prepare the area where the elephant will be treated S tanding sed ation or general anesthesia? Depending on the conditions of the facility, the procedure can be done under : - Standing sedation , using detomi di ne and butorphanol (or xylazine and butorphanol if detomidine is not available). Azaperone can be used as premedication. Xylazine alone has also been used in a range country where detomidine was not available. There must be sufficient access to the working area. Best is to chain the animal to a wall on both legs on the contra-lateral side of the fractured tusk. The use of a belly belt around the abdomen is highly recommended for safety reasons in case the elephant goes down. - General anesthesia is not strictly required, but under certain circumstances it is a good alternative if standing sedation is not an option. Once the animal is secured either in standing sedation or under general anesthesia, the tusk repair can start: Step 1: create sterile workfield 1. Scrub the affected tusk thoroughly using Povidone iodine scrub. 2. Cut off the tip of the fractured tusk using a giggli wire. Keep the soft tissue out of reach of the giggli wire!!! 3. If present, remove all abnormal (black) ivory using the Dremel. 4. Clean and brush the area (tusk and face) with soap and Betadine scrub. Flush with Betadine solution and alcohol (70%). 5. Cover the surrounding, disinfected skin with a sterile surgery sheet (secure with duct tape) 6. Put on surgical gloves and suit. Step 2: filling the pulp canal 7. Cut off 20-50 mm of the pulp tissue (depending on the diameter of the open pulp canal). If any pulp tissue has been pulled out when the tusk fractured, it is assumed that it has been separated from the tusk wall and when it snapped back in, it probably pulled in bacteria. So even if the pulp looks fresh when doing the pulpectomy, i.e., bacteria could be lurking way up the wall of the canal that you can't get to. This is a challenging part of the procedure. The pulp tissue has a rubbery consistency and needs to be cut with very sharp instruments (curved scissors and scalpels). High-speed cutters used in hip replacement procedures in dogs (Acetabular Reamer) have been used . Depending on the diameter of the pulp canal, a decision needs to be made either to fill the pulp canal at this point, or to bring in a threaded rod (or pulp insert plug) to stop the bleeding. If the pulp diameter is less than 5 mm, one can decide to skip the threaded rod method (skip steps 8, 9, 13 and 14). A threaded rod should be used in any pulp canal diameter larger than 5 mm. In that case, follow the entire procedure as written below. The aim of the plug is to stimulate normal dentinal bridge formation proximal to the plug insert. 8. Drill the pulp canal out to a perfectly round cylinder of the proper size, which corresponds with the diameter at the end of the drilled hole. A so-called step drill can be helpful to accomplish this task. 9. Tap threads into the wall of the tusk so that you have full threads of the plug in the tusk, PLUS, at least 2-3 cm of tusk wall above the plug. 10. Stop bleeding by compressing the pulp tissue gently with epinephrine-impregnated gauze (for several minutes). 11. Fill in the canal with Calcium Hydroxide or calcium hydroxy apatite with a push rod, which mixes some with the blood, and occasionally stops the bleeding for a short time. Other calcium sources that have been used successfully are: Calcium hydroxy-apatite paste (made at location by mixing powder with chlorhexidine or sterile water) and milled and sterilized Portland Cement. 12. Once the canal is full, clean out the calcium from the threads (usually the blood is oozing thru by then). 13. Screw in an inert plug. Plugs of different materials have been used, ranging from hardware store drain plugs made of PVC, ABS, polyoxymethylene to even brass. Sizes have ranged from 5-50mm diameter. The blood acts as a lubricant when the plug is screwed in. It also forms a nice clot next to the plug to aid in the formation of the dentin bridge. 14. The plug needs to be recessed at least 10 to 20 mm so tusk repair material can be placed over it. 15. Then flush the small remnant of the pulp canal with Chlorhexidine 1%. 16. Flush again with saline solution. 17. Let dry (if needed, use a hair dryer) 18. ETCHING: rub an etching agent on the dentin wall of the pulp canal (cotton-tip) for max. 15-30 seconds. 3M™ Scotchbond™ Universal Etchant Etching gel is a good choice; phosphoric acid (H3PO4 37,5%) or hypochlorite (NaOCl 3%, bleach) are alternatives. 19. Let dry again; use a hairdryer to reduce drying time. 20. Close the pulp canal with glass-ionomer cement. Fill the canal, but leave 5 mm for the composite. 21. Clean the cut-off side of the tusk or sand it with sandpaper. 22. Apply etching (15-30 sec), rinse again and apply bonding for composite application (e.g. Scotchbond Universal Etchant Etching gel (H3PO4 37,5%) and Scotchbond Universal Adhesive). 23. Cover the cement and surrounding area with a layer of dental composite self-curing or light curing, depending on availability of UV-light source (e.g. Tetric Evo Ceram/MIRIS/Filltek/…). 24. Cover the entire cut-off side of the tusk with epoxy glue for extra protection. 25. The tusk will then gradually wear down and the time the wear reaches the plug, the dentin bridge will have formed. At that point, the plug will usually pop out and if needed the hole can be again filled with your favorite tusk repair material. Final stage of tusk repair showing 5 different layers Photo gallery Right tusk fracture in a 5-yr old Asian elephant bull. No attempts to fill the pulp canal were done, resulting in a bacterial pulpitis. By daily cleaning and flushing the deeper part of the pulp remained healthy, resulting in continuous growth of the tusk for at least 2 years. In the end, t he conservative treatment resulted in complete necrosis of the tusk Tip of the fractured tusk and pulp of the same 5 yr-old Asian elephant bull Left tusk fracture in the same 5-yr old Asian elephant bull with the same development course as the left tusk (tusk necrosis) Tusk fracture in a 9-yr old Asian elephant bull that was successfully repaired. See also case report. Tusk fragments of the same 9 yr-old Asian elephant bull. Tip of the tusk after it was sawn off using a giggli wire. During sawing off the tusk tip, the sulcus was lifted using an elephant hook in order to prevent the giggli wire cutting into the skin. When the tusk tip was removed, a large crack filled with dirt became visible. A 'Dremel' hand tool with an extension cable was used to clean out the dirt from the crack. The diameter of the pulp canal was approximately 5 mm. Hence, no threaded rod was used to fill the pulp canal. Etching of the inner tusk wall was done by swapping hypochlorite on the inner surface. The hypochlorite was rinsed off with saline solution. After a layer of calcium hydroxy apatite was applied on top of the pulp, the pulp canal and the cleaned crack were filled with glassionomer cement, the tusk surface was sealed with dental composite. Despite the fact that it was still growing, this tusk of a 26-yr-old Asian elephant bull was extracted several years after it was fractured. These photos show the completely sealed pulp canal by a naturally forme dentin bridge. The decision to extract the tusk is questionable. List of equipment Instruments G iggli wire + handles Plyer to cut off the gigli wire Dremel + extension cable 20 ml syringes (1, 2, 5, 20 and 40 ml) Nail brush Tooth brush Surgical tool set: scissors (1 curved 1 straight) surgical clamps scalpel handle no.3 + blade no.11 sharp spoon Sterile dishes to prepare dental restauration products. Hair dryer High-speed cutter/acetabulum reamer Electric drill Drills (several diameters) Thread makers (several diameters) Threaded (nylon) rods (several diameters) . See text above) Disposables Surgical gloves Surgical suit Surgical drapes Steri le cotton tips Betadine solution (10%) Betadine scrub Ringer's lactate (or Saline solution) Chlorhexidine 1% Etching products: 3M™ Scotchbond™ Universal Etchant Etching gel or Hypochlorite (3%) Calcium hydroxy-apatite powder (to make a paste) or milled and sterilized Portland cement or calcium hydroxide. Glass-ionomer cement Bonding fluid for dental composite (light curing) Dental composite 2-component epoxy or acrylic resin Cotton tips Non-sterile cotton gauze patches (10x10) to cover the eyes Sterile cotton gauze patches (10x10) Leucoplast Duct tape Sand paper Equipment list Avenir Light is a clean and stylish font favored by designers. It's easy on the eyes and a great go-to font for titles, paragraphs & more. References: Woody A.D., Fagan D.A., Oosterhuis J.E. 2022: Large mammal dental surgery. In: Surgery of Exotic Animals, First Edition. Edited by R. Avery Bennett and Geoffrey W. Pye. © 2022 John Wiley & Sons, Inc. To page top

Tuberculosis is an infectious zoonotic disease with a ubiquitous distribution, caused by Mycobacterium species. The most relevant species that affect mammals belong to the group of Mycobacterium tuberculosis-complex (MTBC). The disease is relevant for elephants under human care, as transmission from man to elephant and vice versa is possible. Being a chronic disease with a long incubation time, the initial stages of the disease are often missed. By Willem Schaftenaar DVM Tuberculosis in zoos Based on positive cultures of trunk washing samples or necropsy results the median point prevalence within the Asian elephant in the USA zoo population between 1997 and 2011 increased was 5.1%, with a range from 0.3% to 6.7%. Similarly, the average annual incidence was 2.4 cases per year, with a range from 0 to 7. Since 1960, a total of 45 cases of MTBC (45 M. tuberculosis) were tabulated in Asian elephants in comparison to only 5 cases in African elephants (4 M. tuberculosis and 1 M. bovis), suggesting a difference in species susceptibility (Feldman et al, 2013). The results of a survey on necropsy reports of 301 Asian elephants and 196 African elephants kept in European zoos in the period from 1980 to 2024 is shown in table 1(Hess, 2021, updated by Willem Schaftenaar, 2024). Table 1. MTBC cases confirmed at necropsy in elephants kept in European zoos from 1980-2024. One case of M. caprae has been reported in a Bornean elephant housed in a zoo in Japan. Another M.caprae case in a European zoo is included in table 1. Tuberculosis in range-countries In countries where contact between man and elephant is close, tuberculosis forms a health risk for both humans and elephants. In a study in Malaysia under 60 elephants in 6 different facilities, the overall seroprevalence of TB amongst the elephants was 23.3% and the risk of seroconversion was significantly higher among elephants with assigned mahouts. The percentage of positive responders among wildlife staff was 24.8% and the risk of infection was observed to be significantly associated with being a zoo employee or elephant handler. These findings revealed a potential risk of TB infection in captive elephants and handlers in Malaysia (Yakubu, 2016). Tuberculosis in free ranging elephants Paudel et al (2020) gave an overview of tuberculosis in free ranging elephants. The first report of TB in wild Asian elephants was from Sri Lanka in 2014. A 35-year-old female elephant was found in a moribund condition in the corridor between Udawalawe and Lunugamwehera National Parks. Three wild male Asian elephants that died between 2007 and 2013 in a wildlife sanctuary in southern India were confirmed to be TB positive. One wild Asian elephant that died of suspected TB lesions in the forest of Rajiv Gandhi National Park, Karnataka, India in 2016, was confirmed as TB positive. The first case of TB infection in wild African elephants was reported in Kenya in. This elephant was an orphaned calf rescued from a national park in Kenya and raised with other rescued orphans and then was eventually released back into the wild. Serology, using STAT-PAK on banked serum samples collected from free-ranging African elephants between 2004 and 2018 in Kruger National Park (KNP) in South Africa showed that 9.3% of 161 elephants tested were MTBC positive (Kerr et al, 2019). MTBC was isolated for the first time from a wild African elephant from KNP in South Africa in 2016 (Miller et al, 2019). Zoonotic aspects Transmission of tuberculosis to elephant caretakers, mahouts or zoo visitors should always be considered as a threat to human health. Once an elephant is suspected of tuberculosis, caretakers should seek medical assistance and be checked for this disease on a regular basis. Transmission to other mammalian species The pathogen can be transmitted to humans and other mammalian species by direct contact, contaminated food and materials. Zoo animals treated by the same animal caretakers can transmit MTBC from a shedding elephant to other species (and vice versa). In a Swedish zoo 4 different M. tuberculosis strains were found in different elephants and other zoo animals in the same period (see diagram below): strain A was present in an Asian elephant, a gibbon and a group of South American tapirs. Strain B was found in 4 Asian elephants, while strain C was detected in a giraffe and one of the elephants that also harbored strain B. Strain D was found in an Asian elephant that also carried strain B (Sternberg et al, 2005). In an Australian zoo, a diseased chimpanzee was diagnosed with tuberculosis caused by a MTBC-strain that was indistinguishable from a strain found in an Asian elephant at the same zoo. Investigations included staff and animal screening. Four staff had tuberculin skin test conversions associated with spending at least 10 hours within the elephant enclosure; none had disease (Stephans et al, 2013). TB-suspected elephants should not be in contact with animals that are considered TB-free. Separate cleaning materials and equipment must be used for TB-suspected elephants. Symptoms Tuberculosis is a slow developing disease. Most elephants with TB are older than 5 years. One of the first signs of clinical disease is persistent weight loss. Often this is the only symptom seen. If no explanation can be found for this chronic weight loss, one should consider TB as its possible cause. Although the lungs are usually the first organs that are affected, respiratory signs are usually not observed. Other organs can also become affected, like kidneys, urinary bladder, GI-tract, uterus, liver pancreas and mesenteries. Metastatic MTBC-granulomas are often found in lymph nodes that drain the affected organ system. The lesions caused by MTBC consist of granulomas. If the immune system of the elephant is functioning well, such granulomatous inflammation can be contained, and a buffer zone of defensive cells can produce a capsula around this process. In old granulomas, the original inflammation tissue can become calcified. Even in such a calcified granuloma, vital Mycobacteria can still be present. The presence of such ‘inactive’ granulomas may go completely unnoticed without causing any visible discomfort. Only immunological diagnostic assays will detect such a silent carrier. Unfortunately, many elephants that become infected with MTBC will develop multiple granulomas often with metastasis to regional lymph nodes. Once a granuloma breaks through into the air-containing space of the lung alveoli or bronchi, the elephant can spread the disease to other elephants, humans or other mammals by direct and indirect contact. Sputum that has entered the lower airways can be brought up into the higher airways and, when swallowed, reach the stomach and intestines. MTBC has been detected in fecal samples. If the infection route is orally, granulomas can develop in the GI tract. MTBC-granulomas in the kidneys, urinary tract, uterus or other organs are the result of bacteremia. Figure 1. Granulomas caused by M.tuberculosi s in an adult African elephant bull. Courtesy: Christian Wenker Figurs 2. Sputum collected from the same elephant bull tested positive for M. tuberculosis in PCR and culture. Courtesy: Christian Wenker Transmission When the granulomas affect the excretion system of the organs, the pathogens can contaminate the environment (sputum, urine, feces, fetal fluids) and transmit the disease to other animals. Transmission by breeding has never been documented in elephants. The trunk is considered a major transmission organ of Mycobacterium spp. originating from the lungs. Nevertheless, it is very difficult to find TB-organisms in trunk washes (see trunk wash procedure ). There are several anecdotal reports that a sputum sample found on the floor was confirmed TB-positive while numerous trunk wash samples from the same elephant had been tested negative. Diagnosis Test samples Any granulomatous lesion that is found at necropsy should be suspected of MTBC. Trunk wash samples are frequently used to monitor elephants for MTBC. The elephant needs to be trained for this procedure. For the description of the procedure, click here . Fluids recovered from the trunkwash must be submitted for PCR and culture. The sensitivity of this procedure is extremely low (1-2%) (Sternberg et al. 2005, Vogelnest et al. 2015), which makes the trunkwash a questionable diagnostic tool. Samples obtained by Broncho Alveolar Lavage (BAL) are considered more sensitive than trunk wash samples. However, one should realize that the probability to target an infected bronchus by the BAL-method depends on the number and severity of the lesions. An elephant suspected of carrying MTBC based on immunological tests, can harbor just one or a few encapsulated granulomas in the lung; BAL-samples taken from the area of such granulomas will yield no MTBC. Click here to read more about BAL. A disadvantage of the procedure is that it requires standing sedation or general anesthesia. Excretions like sputum (see figure 2) urine, feces and fetal fluids in MTBC-suspected elephants (chronic weight loss) should be submitted for culture and PCR. Direct tests The golden standard method to diagnose MTBC is culturing of the pathogen. This requires a lab that is certified to culture this microbe. The culturing procedure can take as long as 6 -10 weeks. The cultured isolates must be spoligotyped and preferably submitted for multilocus, variable-number of tandem repeat analysis (MLVA) and whole-genome sequencing, as described previously (Ruetten et al, 2020, Ghielmetti, 2017). PCR is next in reliability and usually carried out in conjunction with culture. Results can be obtained within one day. Positive results should still be cultured. Acid-fast stain (Zhiel-Neelson) on tissue or swab samples can demonstrate the presence of acid-fast bacteria. Confirmation needs to come from culture. Indirect tests (immunological tests) 1. Tests based on cellular immunity . The WHO recommends the following immunological tests as the first choice (for humans): Interferon Gamma Release Assay (IGRA): PBMCs are stimulated with antigens of MTBC. After incubation the amount of elephant interferon is measured in the supernatant (Angkawanish et al, 2013). This assay is currently being practiced at the Utrecht University for monitoring TB in the European elephant population. Another IGRA has been developed in Japan (Paudel et al, 2016). Skin test: in individuals that have been in contact or still carry MTBC intra-cutaneous injection of MTBC- derived antigens can cause a local reaction of the skin (swelling, redness, warm) after 72 hours. Due to the unique properties of the very thick elephant’s skin, this test is not recommended for elephants (Mikota et.al. 2001). 2. Tests based on humoral immunity DPP = Dual Path Platform Assay VetTB Assay for elephants: antibodies against several MTBC-antigens can be demonstrated in a quick test, which is based on ELISA-technology. Multi Antigene Print Immuno Assay (MAPIA). This test is offered by Chembio (USA) as a confirmation test of the DPP VetTB Assay for elephants. Each antigen that is present in the DPP is individually tested in the MAPIA. ELISA- some local labs had developed their own in-house ELISA. Currently they are not being used. Note: A study in Japan concluded that the discrepancies between serological and IGRA highlight that the two methods may detect different stages of elephant TB. Therefore, employing both tests may enable them to complement each other in correctly identifying elephants that have been exposed to MTBC (Songthammanuphap et al, 2020). Cross reactions Immunological tests have the disadvantage that they do not detect the pathogen itself, but only the immunological reaction of the host to MTBC. Unfortunately, several non-tuberculous Mycobacterium spp (such as M. kansasii, M. fortuitum) have some antigens in common with MTBC. Therefore, one should always take additional circumstances into account when an immunological test turns out positive for MTBC. Chronic weight loss, a history of MTBC in the herd, a caretaker suffering from tuberculosis are factors that can help form a stronger diagnosis than just the outcome of an immunological test. Non-tuberculous Mycobacterium spp. Several non-tuberculous Mycobacteria (NTM) have been identified, e.g. M. intracellulare, M. hominnisuis, M. fortuitum, M.avium, M. flehi, M kansasii. In one study, isolates of M. avium, M. peregrinum, and M. novocastrense, three NTM species, were detected in samples from the lung or mouth (Hermes et al, 2018). One NTM, Mycobacterium szulgai, was associated with mortality in two captive African elephants (Loxodonta africana) (Lacasse et al, 2007). Treatment Treatment of MTBC has been an option when MTBC is confirmed by culture. One should realize, however, that the complete elimination of the pathogen by treatment is not guaranteed. Like in humans, MTBC can remain present in encapsulated foci and relapses after several years have occurred. Treating tuberculosis is expensive, laborious, and needs to be sustained for a long period. As some of the drugs are (nephro)toxic, negative side effects of the drugs need to be monitored closely. The elephant protocol is based on treatment regimens that are used to treat TB in humans. The basic protocol calls for 3-4 drugs for 2 months followed by 2 drugs for 10 months. Isoniazid, rifampin, ethambutol, and pyrazinamide are the first line drugs that are typically used. Administration is oral or rectal although rectal Rx has some limitations. If at all possible, serum drug levels should be monitored. Treatment details can be found in chapter 9 and 10 of the Guidelines for the control of tuberculosis in elephants 2010 . Surveillance Monitoring elephants that have been in contact with other animals suffering of MTBC (including humans) by regular TB-testing is the most effective way to detect an infection. Elephants with a TB-history (treated or in contact with MTBC-positive animals) should not be moved to a TB-free facility. Annual TB-screening of caretakers should be part of the elephant management in zoos. Moving elephants Elephants that will be moved from one zoo to another should be checked before the transfer. Click here for TB-recommendation for European zoos and click here for TB-recommendation for USA zoos. The release of orphaned elephants after rehabilitation in a management system under human care, carries a risk of transmission of tuberculosis to free ranging elephants. The disease may have been present unnoticed during the rehab period. Testing for MTBC prior to release should be a requirement without which no release should take place. Prevention A vaccine against tuberculosis in elephants is not available. The value of BCG-vaccination, used to vaccinate humans in endemic areas, has not been tested in elephants. Even in humans, it only prevents the childhood meningitis form of TB and does not protect against pulmonary TB. Government regulations Though M. bovis is just one of the MTB-complex group, for economic reasons related to the cattle industry, most governments only have strong regulations for cases of tuberculosis caused by M. bovis. In those countries, tuberculosis caused by M. bovis in elephants is notifiable. Because of the zoonotic aspects of the disease it is, however, strongly recommended to contact government officials in any case of confirmed tuberculosis. References Hess A. 2021. 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. Thesis at the Department of Exotic Animal and Wildlife Medicine University of Veterinary Medicine Budapest, Hungary. Updated by Schaftenaar W. 2024. Unpublished data EAZA elephant TAG studbook. Paudel S, Sreevatsan S. 2020. Tuberculosis in elephants: Origins and evidence of interspecies transmission. Science direct: Tuberculosis 123 (2020) 101962. Ruetten M, Steinmetz HW, Thiersch M, Kik M, Vaughan L, Altamura S, Muckenthaler MU and Gassmann M. 2020. Iron regulation in elderly Asian elephants (Elephas maximus) chronically infected with Mycobacterium tuberculosis. Front. Vet. Sci. 7:596379. doi: 10.3389/fvets.2020.596379 Songthammanuphap S, Puthong S, Pongma C, BuakeawA, Prammananan T, Warit S, Tipkantha W, Kaewkhunjob E, Yindeeyoungyeon W, and Palaga T. 2020. Detection of Mycobacterium tuberculosis complex infection in Asian elephants (Elephas maximus) using an interferon gamma release assay in a captive elephant herd. Scientific Reports (2020) 10:14551; https://doi.org/10.1038/s41598-020-71099-3 Kerr TJ, de Waal CR, Buss PE, Hofmeyer J, Lyashchenko KP, Miller M.A. 2019. Seroprevalence of Mycobacterium tuberculosis Complex in Free-ranging African Elephants (Loxodonta africana) in Kruger National Park, South Africa. J Wildl Dis (2019) 55 (4): 923–927. Miller MA, Buss P, Roos EO, Hausler G, Dippenaar A, Mitchell E, van Schalkwyk L, Robbe-Austerman S, Waters WR, Sikar-Gang A, Lyashchenko KP, Parsons SDC, Warren R and van Helden P. (2019). Fatal Tuberculosis in a Free-Ranging African Elephant and One Health Implications of Human Pathogens in Wildlife. Front. Vet. Sci. 6:18. doi: 10.3389/fvets.2019.00018 R. Hermes R, Saragusty J, Holtze S, Nieter J, Sachse K, Voracek T, Bouts T, Göritz F, and Hildebrandt TB. 2018. Bronchoalveolar lavage for diagnosis of tuberculosis infection in elephants. Epidemiology and Infection 146, 481–488. https://doi.org/10.1017/S0950268818000122 Ghielmetti G, Coscolla M, Ruetten M, Friedel U, Loiseau C, Feldmann J. 2017. Tuberculosis in Swiss captive Asian elephants: microevolution of Mycobacterium tuberculosis characterized by multilocus variable-number tandem-repeat analysis and whole-genome sequencing. Sci Rep. (2017) 7:14647. doi: 10.1038/s41598-017-15278-9 Paudel S, Villanueva M.A, Mikota S.K, Nakajima C, Gairhe K.P, Subedi S, Rayamajhi N, Sashika M, Shimozuru M, Matsuba T, ySuzuki Y and Tsubota T. 2016. Development and evaluation of an interferon-γ release assay in Asian elephants (Elephas maximus). J. Vet. Med. Sci. 78(7): 1117–1121, 2016 Yakubua Y, Onga B.L., Zakaria Z, Hassan L, Mutalib A.R., Ngeowc Y.F., Verasahib K, Razak M.F.A.A. 2016. Evidence and potential risk factors of tuberculosis among captive Asian elephants and wildlife staff in Peninsular Malaysia. Preventive Veterinary Medicine Volume 125, 1 March 2016, Pages 147-153. Vogelnest L, Hulst F, Thompson P, Lyashchenko K.P., Vinette Herrin K.A. 2015. Diagnosis and management of tuberculosis (Mycobacterium tuberculosis) in an Asian elephant (Elephas maximus) with a newborn calf. Journal of Zoo and Wildlife Medicine 46(1): 77–85, 2015. Angkawanish T, Morar D, van Kooten P, Bontekoning I, Schreuder J, Maas M, Wajjwalku W, Sirimalaisuwan A, Michel A, Tijhaar E and Rutten V. 2013. The Elephant Interferon Gamma Assay: A Contribution to Diagnosis of Tuberculosis in Elephants. Transboundary and Emerging Diseases. 60 (Suppl. 1) (2013) 53–59. Feldman M, Isaza R, Prins C, Hernandez J. 2013.Point prevalence and incidence of Mycobacterium tuberculosis complex in captive elephants in the United States of America. Vet Q 2013; 33:25–9. Stephans N, Vogelnest L, Lowbridge C, Christensen A, Marks G.B., Sintchenko V, McAnulty J. 2013. Transmission of Mycobacterium tuberculosis from an Asian elephant (Elephas maximus) to a chimpanzee (Pan troglodytes) and humans in an Australian zoo. Epidemiol. Infect. (2013), 141, 1488–1497. © Cambridge University Press 2013 Lacasse C, Terio K, Kinsel M.J, Farina L.L, Travis D.A. D.A, Rena Greenwald, Konstantin P. Lyashchenko, Miller M, Gamble K.C. 2007. Two cases of atypical mycobacteriosis caused by Mycobacterium szulgai associated with mortality in captive African elephants (Loxodonta africana). J. of Zoo and Wildlife Medicine, 38(1 ) :101-107 (2007). Sternberg Lewerin S, Olsson S-L, Eld K, Röken B, Ghebremichael S, Koivula T, Källenius G, Bölske G. 2005. Outbreak of Mycobacterium tuberculosis infection among captive Asian elephants in a Swedish zoo. Veterinary Record (2005) 156, 171-175. Mikota SK, Peddie L, Peddie J, Isaza R, Dunker F, West G, Lindsay L, Larsen RS. 2001. Epidemiology and diagnosis of M. tb in captive Asian elephants. J. Zoo Wildl. Med. 32: 1-16 To page top Tuberculosis Tuberculosis is an infectious zoonotic disease with a ubiquitous distribution, caused by Mycobacterium species. The most relevant species that affect mammals belong to the group of Mycobacterium tuberculosis-complex (MTBC), including M. tuberculosis, M. bovis, M. pinnipedi, M. africanum, M. microti, M. canetii, M.caprae and Bacillus Calmette-Guérin (vaccine). The disease is relevant for elephants under human care, as transmission from man to elephant and vice versa is possible. TB is a chronic disease with a long incubation period, and the initial stages of the disease are often missed.

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