The donkey belongs to the order Perissodactyla, suborder Hippomorpha, family Equidae, and genus Equus. In this genus there is the horse and Przewalski's horse (E. ferus caballus and E. ferus przewalskii); the donkey or ass (E. africanus asinus); the onager or Asiatic wild ass (E. hemionus onager); the plains, common, or Burchell's zebra (E. quagga, formerly E. burchellii); the mountain and Hartmann's zebras (E. zebra zebra and E. zebra hartmannae); and the imperial or Grévy's zebra (E. grevyi). 1 Donkeys and alike, including wild assess were domesticated before the horse and have contributed to social, economic, and cultural advances; religious customs; and human geographic expansion. Donkeys often live longer than horses, and their size, calm and stoic behavior, thriftiness, ability to perform hard work, and resistance to diseases made the donkey the preferred species for pack and draft work. 2, 3 In addition to physical work, donkeys are used for leisure and touristic activities; are a source of food (meat and milk) in some countries; their byproducts are used in the cosmetic industry; and more recently, donkey-assisted therapy is being used for people with mental and physical disabilities. 4 Because of its claimed hypoallergenic properties, excellent palatability, and nutritional value, donkey milk has been proposed to be a good breast milk substitute for infants with allergic disorders. 5 Asinotherapy (onotherapy) is gaining popularity in treating and supporting people with mental and emotional disorders (Alzheimer's disease, autism, attention deficit hyperactivity disorder, and Down syndrome) and physical disabilities as well as in geriatric medicine as a therapeutic tool to improve physical and mental health and quality of life. 6 Behavioral tests to select donkeys for this purpose have been developed. 7 Because interest in donkeys by the general public is increasing, it is important to generate donkey-specific information to provide better veterinary care. When facing the diagnosis and treatment of pathologic conditions of donkeys and asses, it should be considered that there are anatomic, physiologic, and metabolic differences from horses. From this perspective, extrapolating data for diagnostic and therapeutic purposes could be fine in most instances, but in others it may lead to misdiagnosis and unnecessary or inadequate treatment.
When their electrocardiogram is compared to horses' , donkeys display shorter P waves (lead II), pronounced QRS complexpositive waves, and different QRS vectors, which could be related to cardiac size or cardiac location relative to the thorax. [8] [9] [10] Tricuspid and mitral peak flow velocities are lower in donkeys than horses. 11, 12 These values must be taken with caution because they are likely influenced by breed, age, size, and fitness. Donkey gender and body weight affect cardiac dimensions on two-dimensional and M-mode echocardiography. 13 Standardized imaging protocols for M-mode and Doppler measurements described for horses also apply to donkeys. [11] [12] [13] A low prevalence of cardiac diseases in donkeys was reported. 14 Third-degree atrioventricular block seems to be a common cardiac conduction disorder in donkeys, particularly in small breeds. 15 It has been reported that 2% of donkeys have an audible murmur, 14 which is lower than horses (50%-80%). 16 
Respiratory disorders documented in horses also affect donkeys, although the presentation and severity of signs varies. Because of their stoic nature, signs of respiratory disease in donkeys tend to be less evident, and when present, the disease process is often advanced. Lower respiratory tract cytologic distribution is similar between donkeys and horses. 17, 18 Pulmonary fibrosis and tracheal collapse are common in geriatric donkeys. 19, 20 An association between tracheal collapse and pulmonary fibrosis has been proposed. 21 Asinine herpesvirus 4 (AHV-4) and AHV-5 have been isolated and proposed as potential causative agents. 22 One can speculate that this condition is equivalent to equine multinodular pulmonary fibrosis, which has been linked to equine herpesvirus 5 (EHV-5) in horses.
Donkeys and mules can be reservoirs for infectious and parasitic diseases that affect horses (e.g., herpesviruses, lungworms). Therefore, their cohabitation can be problematic, particularly in farms with poor sanitary management or frequent animal movements. 23 Influenza is the most common respiratory infectious disease in donkeys 24 and they are apparently more susceptible than horses to the influenzavirus. 25 A PPE N DI X I
Francisco J. Mendoza, Ramiro E. Toribio, and Alejandro Perez-Ecija Donkeys can be infected by EHV-1 and EHV-4, 26 as well as specific asinine herpesviruses (AHV-1, AHV-2, AHV-3, AHV-4, AHV-5, and AHV-6). Not every asinine variant causes clinical respiratory disease in donkeys. Mules can be infected but rarely show signs. 27 There are no vaccines for AHVs, and vaccination protocols are based on the use of vaccines for horses.
Based on serologic surveys, donkeys and mules develop antibodies against equine arteritis virus (EAV). 28 However, naturally occurring EAV has not been reported in donkeys or mules. There are donkey-specific EAV strains (asinine-94) with limited transmission to horses, 29 but reports of clinical disease in donkeys are lacking. Fever, mild depression, nasal and ocular discharge, conjunctivitis, and dependent edema were reported in donkeys experimentally infected with the KY-84 strain. 29 Donkeys and mules appear to be more prone to glanders (Burkholderia mallei) than horses. 30, 31 African horse sickness is less severe and rarely fatal in donkeys, 32 which may have epidemiologic implications, because donkeys and mules can act as carriers. 33 Donkeys can host high numbers of adult lungworms (Dictyocaulus arnfieldi) with minimal to no clinical signs compared with horses, thus, acting as carriers. Prevalences of 68% to 87.5% for donkeys and 29% for mules were reported. 34, 35 Therefore having horses and donkeys grazing together should be avoided, particularly when a parasite control program is not established. Diagnosis is achieved via fecal examination (Baermann method), and bronchoalveolar cytology may show eosinophilic inflammation and larval stages. Macrocyclic lactones and benzimidazoles are effective against D. arnfieldi. 36
A recent report based on postmortem examination of aged donkeys at a sanctuary described a 40% prevalence of gastric ulcers. 37 A gastric ulcer scoring system for donkeys has not been developed, but the one for horses seems valid. Draschia megastoma is considered the most pathogenic gastric parasite in donkeys. 37 For equivalent intestinal lesions, donkeys exhibit less pain than horses, which is a factor that should be taken into consideration when deciding management, including exploratory laparotomy. In a large population of donkeys, among all types of colic, the prevalence of large colon impaction was 55% and the mortality risk was 51%. 38 The prevalence of enteroliths is geographic and is more frequent in areas with hard water and access to alfalfa (e.g., Mediterranean basin, California). 39 Donkey-specific information on drugs that influence gastrointestinal function, including gastric secretion, is scarce. Management of colitis relies on the same principles as for other equids.
Donkeys can handle water deprivation longer than horses, 40 and their tolerance to dehydration has been equated to that of camels and Zebu cattle. 41 Dehydrated donkeys when allowed free access to water are very effective at restoring their hydration status, with minimal risk for overhydration.
Donkeys are thrifty animals, with low energy requirements and a natural ability to digest poor quality forages. [42] [43] [44] [45] Concentrates and caloric-rich diets are unnecessary and should be avoided unless the animal is performing heavy work.
Hyperlipemia. The prevalence of dyslipidemias is higher in donkeys (10%-20%) than horses and ponies, with higher mortality rates (up to 80%). 42, 46 Liver disease (19.4%) followed by colic (13.8%) was the most common condition in 449 dyslipidemic donkeys. 47 Transport can be stressful for some donkeys, which may explain their susceptibility to hyperlipemia after transportation. 48 For details on the pathogenesis of hyperlipemia, see Chapter 13.
Baseline triglyceride concentrations (range: 53-248 mg/dL; 0.6-2.8 mmol/L) in healthy donkeys are higher than values reported for healthy horses and ponies. 49 Serum leptin concentrations in healthy donkeys (2.7 ± 0.3 ng/mL) are similar to values reported for horses. 50 Therapeutic principles of hyperlipemia in small equids apply to donkeys.
Pathophysiologic principles of obesity, insulin resistance, metabolic syndrome, endocrinopathic laminitis, and pituitary pars intermedia dysfunction (PPID) apply to donkeys 50,51 ; however, donkey-specific information for these conditions is minimal.
Donkey or Asinine Metabolic Syndrome. Obesity is common in donkeys in developed countries. When high-quality or calorie-rich feed is provided, donkeys easily accumulate adipose tissue. From the equine perspective, they can be considered "easy keepers. "
A donkey-specific Body Condition Scoring (BCS) system ranging from 1 to 9 points (<3 = underweight; 4-6 = optimal condition; >7 = overweight) has been developed. 51 The Donkey Sanctuary, a charitable organization in England, developed a formula to estimate body weight in donkeys. For adult donkeys, weight (kg) = 0.000252 × height 0.24 × heart girth 2.575. 52 In donkeys younger than 2 years of age, the formula is weight (kg) = 0.000283 × heart girth 2.778. 52 A neck scoring system for donkeys has also been developed. 51 This score ranges from 0 (thin neck without palpable crest) to 4 (thick neck, rounded, cresty).
A link between obesity, insulin resistance, and laminitis has been documented in donkeys. 53 However, detailed information on asinine metabolic syndrome (AMS) and insulin resistance is limited. Other signs of equine metabolic syndrome reported in horses, such as hypertension or reproductive disturbances, have not been documented in donkeys. Insulin concentrations are often high in obese donkeys, suggesting insulin resistance. Unlike horses, hyperinsulinemia as a direct cause of laminitis has not been demonstrated in donkeys. 54 Similar to horses, geriatric donkeys have lower insulin concentrations that could result in reduced β-cell mass or less β-cell sensitivity to glucose. 51 The diagnosis of insulin resistance relies on the same principles for horses. Few studies have evaluated glucose and insulin dynamics in donkeys. 53, [55] [56] [57] In one study, insulin concentrations >20 μIU/mL were associated with laminitis. 58 The clinical relevance of this or higher insulin cutoff values to diagnose insulin resistance and evaluate their risk for endocrinopathic laminitis remains unclear. Reference values for glucose ratios and surrogates have been described in healthy donkeys. 57 When dynamic diagnostic testing is performed in donkeys, validated protocols should be used. 56, 57, 59, 60 Donkeys have an inherently delayed insulin-mediated glucose uptake compared with horses and ponies. 57 Their glucose curve is right-shifted in the combined glucose insulin test (CGIT), intravenous glucose tolerance test (IVGTT), and oral glucose tolerance test compared with horses. 59, [61] [62] [63] These differences support delaying glucose sampling for 60 or 75 minutes in donkeys versus 45 minutes for horses in the CGIT and for 150 minutes in the IVGTT. 64 Serum leptin concentrations are higher in donkeys with high BCS and neck scores, 51 as well as in old donkeys compared with young donkeys. 51 The association between blood adiponectin, glucagon, ghrelin, and insulin growth factor-1 concentrations with age, gender, and obesity was recently reported in healthy donkeys. 51 Specific treatments for AMS are not described, but principles for horses seem to apply. Grazing should be reduced when pastures may be rich in carbohydrates. A grazing muzzle could be useful in some animals. A weight-loss program should be oriented toward reducing body weight by 2% monthly until an optimal weight and BCS are achieved. Pharmacologic treatments used in horses to promote weight loss and increase insulin sensitivity have not been critically evaluated in donkeys.
Pituitary Pars Intermedia Dysfunction. Epidemiologic information for PPID in donkeys is lacking. PPID is more prevalent in donkeys older than 15 years of age. 65 No gender or breed predisposition has been demonstrated.
Clinical signs are similar to horses, with hypertrichosis (hirsutism) being the most frequent sign, considering that the hair-coat is longer and the hair is thicker in donkeys than horses. Laminitis, insulin resistance, abnormal fat distribution, and muscle wasting (sarcopenia, potbelly) are also signs of PPID in donkeys. Polyuria is rarely seen. Other signs described for horses (reproductive disturbances, blindness, seizures, secondary infections, and lethargy) have not been reported in donkeys. 65 The diagnosis of PPID in donkeys is based on protocols described for horses. 65 Basal plasma cortisol concentrations in healthy donkeys and horses are similar 66 ; however, adrenocorticotropic hormone (ACTH) concentrations are higher in donkeys than in horses. 66 This indicates that using equinespecific ACTH cutoff values for a healthy donkey could potentially cause misdiagnosis of PPID. Seasonal ACTH reference values for donkeys have not been generated. Dynamic diagnostic testing protocols for PPID in horses (the thyrotropin releasing hormone stimulation test) also appear to be valid for PPID donkeys. 67 Based on clinical results, pergolide dosing for horses also works in donkeys with PPID.
Thyroid Gland Diseases. Information on thyroid gland disorders in donkeys is minimal. Thyroxine (T4) and triiodothyronine (T3) concentrations are occasionally measured, but result interpretation can be misleading. Healthy donkeys have higher plasma free T3, total T3, free T4, total T4, and reverse T3 concentrations than horses. 68 This is a good example in which values from horses should not be extrapolated to donkeys because it could lead to misdiagnoses. Sexual dimorphism for thyroid hormones has not been demonstrated in donkeys or horses. 69, 70 Similar to horses, 71 age affects thyroid hormones, with younger animals having higher thyroid hormone concentrations. 68 Drugs known to reduce thyroid hormone concentrations, such as phenylbutazone and glucocorticoids, should be taken into consideration for data interpretation, [72] [73] [74] particularly if these drugs have been administered within a month of testing.
The neurologic examination of donkeys with mild spinal ataxia can be challenging for multiple reasons, including differences in gait, type of lesion, and spinal cord response to disease. Cervical stenotic myelopathy is uncommon in donkeys and mules but may develop from developmental, traumatic, or inflammatory processes. Information on viral (Borna; EHV-1; rabies; coronavirus; West Nile virus; Japanese viral encephalitis; and Eastern, Western, and Venezuelan equine encephalitis), [75] [76] [77] [78] [79] [80] [81] bacterial (e.g., neuroborreliosis or Lyme disease), 82 and parasitic (e.g., Neospora spp., Strongylus vulgaris) 83,84 disorders of donkeys is lacking. Clinical signs of Venezuelan equine encephalitis are usually mild in donkeys and mules, 85 but they could act as amplifying vectors, propagating the virus to horses and people. There are no published cases of equine protozoal myeloencephalitis (Sarcocystis neurona) in donkeys, and they are considered to be relatively resistant to the disease. 86 Nutritional and metabolic imbalances leading to neurologic disorders have been reported in donkeys and mules. Signs similar to equine degenerative myelopathy from vitamin E deficiency were reported in donkeys. 87, 88 
Urinary tract diseases are uncommon in donkeys, with urolithiasis being the most common. [89] [90] [91] [92] In one postmortem survey of renal lesions in 100 donkeys, tubulointerstitial nephritis (50%), cystitis (19%), and renal fibrosis and cysts (13%) were the most common lesions found in the urinary tract. 89 Dysuria, stranguria, pollakiuria, hyperkalemia and hyponatremia, and urinary tract infections were common signs of urinary tract disease in donkeys. 89, 90 Most drugs used in horses and ponies to treat renal disease have not been investigated in donkeys, and dosing protocols are derived from horses.
Corneal ulceration is the most frequent ocular pathology in donkeys. 93, 94 Equine recurrent uveitis prevalence seems to be lower in donkeys than horses, which could be explained by a lower predisposition to this condition or reflect infrequent ocular examinations in donkeys. 95 Old donkeys are prone to lens pathologies such as cataracts and luxation 96 or even colobomas. 97 Nonulcerative eosinophilic keratitis was reported in mules and donkeys. 98 Ocular parasites described in donkeys include Onchocerca spp. 99 and Setaria equina. 100 Habronemiasis mainly affects the conjunctiva and occurs sporadically. 93 Blindness can go unnoticed in donkeys, which likely reflects their ability to memorize their surroundings better than horses.
Congenital dermatoses such as junctional epidermolysis bullosa, 101 epitheliogenesis imperfecta, or an Ehlers-Danlos-like syndrome 102 have been documented in donkeys. Immune-mediated dermatopathies are rare in donkeys. Pemphigus foliaceus was reported in a pregnant jennie. 101 Atopic dermatitis, characterized by pruritus and urticaria on the face, trunk, and legs, was reported in a Miniature donkey. 103 Traumatic skin lesions are a frequent problem in working donkeys.
Sarcoids are frequent cutaneous tumors in donkeys. Invasive and fibroblastic types are the most reported in donkeys, whereas the occult and verrucose forms are rare. 102 Other skin tumors of donkeys include squamous cell carcinomas, fibromas, fibrosarcomas, melanomas, and epitheliotropic lymphomas. 104 Melanomas are usually located in periocular areas and rarely related to haircoat color. Squamous cell carcinomas tend to be ocular and are less frequently located in the oral and nasal cavities, prepuce, vulva, or proximal gastrointestinal tract.
There are foot anatomic and radiologic differences between donkeys and horses. 105 For a more detailed description of the donkey hoof, see Thiemann and Rickards. 106 Foot lesions are the main cause of lameness (65% of the cases), and endocrinopathic laminitis is the main one. 107 Pedal abscesses are the second cause of lameness in donkeys. Long hooves are a frequent cause of coffin bone remodeling. White line disease, interphalangeal joint contracture, luxations, and keratomas are infrequent problems. 106, 108, 109 Hip fractures and coxofemoral luxations in small-to medium-sized donkeys (<250 kg) may be seen sporadically. 110, 111 Deep and superficial digital flexor tendinitis (23%-47%), suspensory desmitis (16%-31%), and digital flexor tendon sheath swelling (62%-77%) are the main soft tissue problems associated with lameness. Exertional rhabdomyolysis, polysaccharide storage myopathy, grass sickness, and atypical myopathy have been described in donkeys. [112] [113] [114] [115] [116] Y CLINICAL PATHOLOGY Interpretation of hematologic and biochemical information using equine reference values can be misleading because of the lack of donkey-specific information in most veterinary laboratories.
Hematologic variables from donkeys are listed in Table A. 1. The donkey red blood cell (RBC) count tends to be lower, but erythrocytes are larger than in horses. RBC count, hematocrit (HCT), and hemoglobin (Hb) values are closer to ponies than horses. 129 Reticulocytes are not found in peripheral circulation. Large-and medium-sized lymphocytes are more frequent in blood smears from donkeys than horses. Eosinophils and basophils are slightly larger in donkeys.
No effect of gender on hematologic variables has been documented. RBC, HCT, and Hb concentrations are higher in newborn donkey foals and then decrease in the first week postpartum. 130 Erythrocyte volume, corpuscular Hb concentration, and red cell distribution width remain unchanged in the first week of life. White blood cell count is lower in the immediate postpartum period, ranging from 4 to 12,000/μL (birth to day 3) to 6 to 15,000/μL (days 3-7). 130 The neutrophil:lymphocyte ratio can be as high as 2.8 at birth in donkey foals, but it declines to 1 by 12 months of age. Eosinophils and basophils change minimally in the first weeks of life, although their numbers tend to be higher than those for equine foals. Platelet parameters do not change in the first week of life, and the platelet number is higher than in adults.
Neonatal isoerythrolysis is a frequent problem in mule foals. 131 The presence of a donkey-specific erythrocyte antigen (donkey factor) is suspected to be responsible for this disorder. Considering that horses do not have alloantibodies against the donkey factor, mule foals with isoerythrolysis could receive blood transfusion from a horse with no history of breeding to donkeys. Washed erythrocytes from the dam can also be used. Neonatal alloimmune thrombocytopenia is an occasional finding in sick newborn mules. This condition usually develops within 24 to 48 hours after colostrum ingestion. 132 Immune-mediated thrombocytopenia can be a serious complication in donkey foals receiving plasma transfusion of equine origin.
Biochemical variables from a number of studies are listed in Table A .2. Hepatic enzyme activities and bilirubin concentrations are lower in donkeys compared with horses, whereas creatine kinase, γ-glutamyl transpeptidase, and plasma triglyceride concentrations are higher in donkeys. 130 In one study, jennies had higher aspartate aminotransferase activity, total protein, total calcium, and indirect bilirubin concentrations, whereas male donkeys had greater alkaline phosphatase activity, albumin, phosphorus, glucose, creatinine, cholesterol, magnesium, and ionized calcium concentrations. 135 Pregnancy, foaling, and lactation can influence biochemical variables. 136 There are age-related differences for a number of biochemical variables. 130 Coagulation profiles vary between donkeys and horses. 137 Fibrinolytic subproducts (fibrin/fibrinogen degradation products [d-dimers]) were higher in healthy donkeys compared with horses. 137 Y PHARMACOLOGY Drugs commonly used in horses do not necessarily have similar pharmacokinetic and pharmacodynamic properties in donkeys and mules, and donkey-specific information is lacking (Tables A.3 and A.4). Depending on the drug, caution must be used when extrapolating doses and frequency from horses to avoid inadequate dosing and toxicity.
There are differences in nonsteroidal antiinflammatory drug metabolism between donkeys and horses (Table A. 3). 163 Phenylbutazone has a shorter half-life in Miniature donkeys, requiring shorter treatment intervals compared with regularsized donkeys and horses. 164 Flunixin meglumine showed an earlier entrance of the drug into the exudate in donkeys compared with horses, although its maximal concentration and durability was shorter. 165, 166 Information on steroid pharmacology in donkeys is lacking.
There are pharmacologic data for a number of antimicrobial drugs in donkeys (Table A.4 ). Donkeys show a higher metabolism for most antibiotics, with faster clearance rates and shorter half-lives for many of them compared with horses (Table A. 
Pharmacologic data for antiparasitic drugs used in donkeys are compiled in Table A .5. It is important to note that most of these drugs are not approved by regulatory agencies for the specific use in donkeys. Close monitoring is indicated for drugs lacking species-specific literature. Donkeys are more sensitive to imidocarb toxicity than horses, so lower doses are recommended. Caution must be taken with macrocyclic lactones, particularly in animals in poor body condition, because of the risk of neurologic toxicity. 