Primate Medicine and Surgery
American Association of Zoo Veterinarians Conference 2008
Geoffrey W. Pye, BVSc, MSc, DACZM
Veterinary Services - San Diego Zoo, San Diego, CA; Consultant, Veterinary Information Network

Taxonomy

Primates can be divided into these major groups: the prosimians (lemurs, lorises, etc), the New World primates (marmosets, tamarinds, squirrel monkeys, spider monkeys, etc.), Old World primates (baboons, mandrills, macaques, colobus, etc.), and the apes (gibbons, siamangs, orangutans, gorillas, chimpanzees, and humans).

Anatomy, nutrition, Reproduction, and Physiology

Anatomy is similar to humans, but individual taxa can have their own unique anatomy. Examples include: New World primates have round nostrils that face the ears while Old World primates have rounded nostrils that face downwards. Most New World primates have a prehensile tail, while Old World primates do not. Female spider monkeys have an elongated clitoris that is frequently mistaken as a penis. Colobines have reduced D1 on the front limbs and spider monkeys have none. The great apes have air sacs that vary in complexity between species. The dental formulae of the broad taxa is as follows: prosimians I 2/2, c 1/1, p 3/3, m 3/3; callitrichids I 2/2, c 1/1, p 3/3, m 2/2; New World monkeys I 2/2, c 1/1, p 3/3, m 3/3; Old World monkeys I 2/2, c 1/1, p 2/2, m 3/3; and apes I 2/2, c 1/1, p 2/2, m 3/3.

Basic non-human primate physiological processes are also generally considered similar to that of humans. A notable difference is in the prosimians which have a low basal metabolic rate [the body temperature for lorises is 95.5-96.3°F (35.3 - 35.7°C)]. Basking and huddling behaviors (lemurs) therefore relate to conserving energy.

Primates generally have one of three types of gastrointestinal tracts dependent upon the type of diet they naturally consume: a standard omnivorous or carnivorous gastrointestinal tract, a hindgut-fermenting gastrointestinal tract (an enlarged cecum/colon for the fermentation of leaf material; howler monkeys and some prosimians), or a foregut-fermenting gastrointestinal tract (an enlarged sacculated stomach; Colobines). There are many nutritive strategies employed by primates. Examples include: squirrel monkeys are insectivorous and frugivorous, spider monkeys are primarily frugivorous, marmosets and tamarinds vary through being frugivorous, omnivorous, and gumnivorous depending upon the species, capuchins are primarily frugivorous with seeds and leaves being seasonally important, and macaques are omnivorous, but primarily frugivorous.

The nutritional requirements for most species of primates has not been determined, but the NRC nutrient requirements for non-human primates have three groupings for soluble (NDF) and insoluble fiber (ADF) intake: 10% NDF & 5% ADF for many New World primates and macaques, 20% NDF & 10% ADF for chimpanzees and ruffed lemurs, and 30% NDF and 15% ADF for Colobines and howler monkeys. The amounts of starch fed to foregut-fermenters needs to limited, as rapid microbial fermentation of simple carbohydrates can cause bloat, foregut inflammation, and diarrhea. Colobines do not ruminate and so there is no opportunity for additional mechanical degradation of very fibrous foodstuffs such as high lignin browse (e.g. acacia). Browse containing large amounts of lignin should therefore be limited to prevent phytobezoar formation.

Protein requirements for non-human primates will vary with stage of life (growth, pregnancy, lactation) as well as health status. Though taurine can be endogenously synthesized, young infants of any species are thought to need exogenous taurine sources because the synthetic pathways for taurine may be poorly developed. Both linoleic and linolenic acids are considered essential fatty acids for non-human primates similar to humans.

Vitamin D is not an essential dietary component as long as animals have adequate exposure to sunlight. Otherwise dietary supplementation or exposure to artificial ultraviolet radiation is needed. While the mechanisms are not completely understood, vitamin D2 is not utilized as efficiently as vitamin D3 in New World primates versus Old World primates. Therefore in situations with inadequate exposure to sunlight, a dietary source of vitamin D3 is required. Most primates are unable to synthesize vitamin C due to a lack of the enzyme gulonolactone oxidase (prosimians are the exception as they have gulonolactone oxidase activity in the liver.

When hand-rearing is required, human products (e.g. Enfamil) are commonly used. Liquid formulations appear to be better as the powdered products have been associated with constipation in some species. The low iron formula is generally offered for the first 30 days and then the iron-fortified formula is offered (neonates may get constipated on the iron-fortified formula initially). Diluting with an oral electrolyte solution to start with is advised.

Only ~14% of primate species are monogamous breeders (e.g. gibbons, siamangs). Other species have social groupings where one or more males are reproductively active with multiple females. New World primates do not mense. Old World primates do mense. The estrus / menstrual cycle of primates typically occur every 28-53 days. Many female Old World primates have sex skin associated with the perineum. Macaques, baboons, and mangabeys demonstrate notable sexual skin swelling. This sex skin undergoes cyclical swelling associated with hormonal changes during the menstrual cycle. Human pregnancy tests (chorionic gonadotropin) can be used for pregnancy diagnosis in gorillas, orangutans, and chimpanzees. New World and Old World primates generally have singleton births, except for the callitrichids in which twinning is common. Prosimians frequently give birth to multiple offspring.

Contraception is fairly straightforward when reversibility is not desired (castration, vasectomy, tubal ligation, and ovariectomy). The most common methods of reversible contraception in primates are hormonal. Medroxyprogesterone acetate injections need to be given every 2-3 months at a dose of 5 mg/kg IM however New World primates may require doses as high as 25 mg/kg. Melengestrol acetate (MGA) implants are placed subcutaneously and have a 2 year life span. Be aware that progestins can be cause weight gain. Human oral contraceptive formulations are commonly used in apes, however incomplete compliance can result in contraceptive failure. Information on contraceptive recommendations for primates as well as other species can be found on the St Louis Zoo's website http://www.stlzoo.org/.

Regulatory Issues

The following agencies have legislation that covers non-human primates: The U.S. Department of Agriculture, Animal Plant Health Inspection Service (APHIS), Regulatory Enforcement and Animal Care (REAC) division oversees the Animal Welfare Act (a written enrichment plan for primates is required: see http://www.nal.usda.gov/awic/pubs/primates/primate2.htm). The Veterinary Services division of APHIS oversees regulations concerning the transportation of animals. The U.S. Department of the Interior - U.S. Fish and Wildlife Service (USFW) oversees the enforcement of US and foreign regulations protecting wildlife (e.g. Endangered Species Act and Convention on International Trade in Endangered Species [CITES]). The U.S. Department of Health and Human Services, Public Health Service (PHS), Centers for Disease Control (CDC) oversees the Public Health Service Act which addresses regulations for the importation on non-human primates. The Department of Treasury, US Customs Service assists PHS with the enforcement of regulations that oversee the importation of non-human primates. Each state may or may not have their requirements overseeing permits, importation of non-human primates, or housing non-human primates.

AVMA Position Statement on Canine Removal / Reduction in Primates

"The AVMA is opposed to removal or reduction of canine teeth in captive nonhuman primates or exotic and wild (indigenous) carnivores, except when required for medical treatment or scientific research approved by an Institutional Animal Care and Use Committee. Reduction that does not expose the pulp cavity may be acceptable. Removal of these teeth or reduction that exposes the pulp cavity, without endodontic treatment, may result in oral pathologic conditions and pain. To minimize bite wounds, recommended alternatives to dental surgery include behavioral modification, environmental enrichment, and changes in group composition."

AVMA Position Statement on the Removal of the Tail from Prehensile Monkeys

"The AVMA is opposed to the surgical removal of the tails of prehensile-tailed monkeys. The tail of this type of monkey serves as an essential appendage, and veterinarians should not remove it either for cosmetic purposes or for the owner's convenience."

Manual and Chemical Restraint

Manual restraint is difficult in many primates due to their strength and ability to bite. Thick gloves are recommended. Restrain the primate by holding the forelimbs around the biceps, pulling the arms directly towards the mid-back. Chemical restraint is advised for most procedures. Small primates may be induced using a facemask and isoflurane. Medium to large primates will require an injectable anesthetic initially. Ketamine at 5-15 mg/kg IM works well in a variety of primates. There is a loss of the bite reflex at low doses, but they can maintain the pharyngeal reflexes making it difficult to intubate without supplemental anesthesia. The addition of midazolam 0.05-0.1 mg/kg or medetomidine 0.01-0.03 mg/kg or tiletamine / zolazepam 1.0-1.5 mg/kg IM can help relax the primate as well as reduce the ketamine dose.

For primates of sufficient size, intubation is recommended. A face shield should be worn as coughing can occur when the laryngeal tissues are stimulated. Primates typically have narrow, short tracheas and so choose a narrower, shorter tube than you would for dogs of a similar size. After intubation, check for accidental single bronchial intubation by bagging the animal and listening for bilateral breath sounds and/or using chest radiographs. Primates may be intubated in a sitting up position with the head and neck extended upwards or "ER-style" on their backs with the head and neck extended.

Analgesia is best provided in a multi-modal, pre-emptive manner. Injectable opioids and NSAIDs in addition to local anesthetics will provide significant analgesia. Buprenorphine (0.005-0.01 mg/kg IM), meloxicam (0.1 mg/kg IM or PO), ketoprofen (2 mg/kg IM) or ibuprofen, naproxen, tramadol, and aspirin at doses extrapolated from human doses are effective analgesics in primates.

Diagnostics

Blood collection is often performed under anesthesia from the femoral vein, but cephalic and jugular vessels can also be used. The caudal saphenous vein can be used for IV catheterization in many species.

Surgery

Repairing traumatic wounds and implanting contraceptives are the most commonly performed surgical procedures in primates. Traumatic wounds typically heal rapidly in primates; particularly if the wound is kept clean and non-infected. Small wounds may be allowed to heal by secondary intention. Larger wounds are sutured; fresh wounds are closed, older infected wounds are only tacked together to allow drainage. Suture picking is common in primates. Hence intradermal skin closure is usually performed. Tissue glue may be used to provide complete closure. The placement of "distractors" can be useful in preventing surgical site picking. "Distractors" include the placement of single interrupted absorbable sutures in the skin well away from the surgical site, the painting of finger or toe nails with nail polish, and the application of small pieces of sticky bandage to the skin or hair away from the surgical site.

Vasectomy and tubal ligation are recommended in primates in group situations to control reproduction, as they allow for normal hormonal activity. It may be argued that a female primate in her natural environment would not normally be cycling repeatedly without conceiving making this an unnatural situation; however, with the hormones present, the group dynamics appear to remain unaltered. Castration and ovariectomy are also performed; typically when group dynamics are not of consideration.

Vasectomy involves removing a portion of the vas deferens. A scrotal or pre-scrotal / inguinal approach may be utilized. The scrotal approach is easier. However, the inguinal skin appears to be less sensitive and if the incision is made in this location, patients appear to be less likely to traumatize the incision postoperatively. Generally, the spermatic cord can be palpated in the inguinal region after it leaves the inguinal canal and before it enters the scrotum. A 1-2 cm incision is made in the skin overlaying the cord. In most cases, fat will be encountered. Dissect through the fat and identify the spermatic cord. The vaginal tunic encloses the vas deferens and the testicular vessels. Make an incision in the tunic and identify the vas deferens. Two hemostatic clips or ligatures are applied about 1 cm apart. The isolated section is then excised. For the scrotal approach, bilateral transverse incisions can be made in the proximal scrotum. Sperm granulomas have been reported following vasectomy. Following vasectomy, males remain fertile for 3-4 weeks and should not be put with females during this time period. Castration is most easily performed through bilateral transverse scrotal incisions. Ligation and closure is routine.

Tubal ligation involves either ligating or removing a section of the oviduct to prevent the ovulated ovum from reaching the uterus. A ventral midline celiotomy provides adequate exposure. A "bikini incision" may be made in which a transverse abdominal skin incision is made and a linea Alba incision is then made in the body wall. In this manner there is little risk of evisceration postoperative as the skin and body wall incisions are perpendicular to each other. The uterus of primates is not bicornuate. The uterus is identified and at the cranio-lateral aspects of the uterus, the oviducts can be found. They are relatively long and easily manipulated. Elevate an oviduct and apply a clip or ligature. If a section is to be removed, apply two clips or ligatures about 1 cm apart and excise the oviduct between them. A simple continuous suture pattern can be used in the linea Alba. Subcutaneous tissues are closed and then an intradermal closure of the skin is performed. Ovariohysterectomy is not routinely recommended in primates due to the anatomy of the reproductive tract and the difficulty in ensuring that the ureters / bladder are preserved intact. Consequently ovariectomy or tubal ligation is recommended. The approach for an ovariectomy is similar to that for tubal ligation. The ovary is located and hemoclips are applied and the ovaries are removed. Closure is the same as in tubal ligation.

MGA contraceptive implants are typically placed interscapular. A stab incision is made in the skin and a pocket made in the subcutaneous tissues away from the incision. A single cerclage of orthopedic wire can be applied around the MGA implant to allow radiographic location of the implant and the twist in the wire can help prevent migration of the implant. Needle-applied implants (e.g. deslorelin) are typically placed subcutaneously in the region of the inner forearm or upper arm. The needle site can be glued closed.

Diseases

Periodontal disease is common in primates with some species (e.g. lorises, Colobines, great apes) being more prone the others. Routine dental examinations (including dental radiographs) and prophylactic cleanings are recommended. Chronic low-dose doxycycline therapy has been shown to be useful in the treatment of periodontal disease in primates. Following dental cleaning and systemic antibiotics as indicated, doxycycline 0.3 mg/kg is given orally twice daily in a pulsatile regime of 3 months on, 3 months off medication. This treatment has been successful in great apes, old world monkeys (including fore-gut fermenters), and prosimians.

Most primates in the wild and in captivity carry viruses and there are about 200 or more viruses that are capable of infecting primates, though not all cause clinical disease in each species of primate. Viruses rarely cause clinical disease, but when they do, it is often quite dramatic in morbidity and mortality. Viral diseases in primates tend to cause encephalitis, hepatitis, hemorrhagic disease, skin disease, tumors, or respiratory disease. Viral diseases in primates tend not to cause blindness, abortion, and infertility. Herpes B virus is zoonotic and is carried by Asian macaques and can cause fatal disease in humans and a variety of monkeys. It is important to note that there can be viral shedding without lesions and in serologic-negative animals. Personal protective gear should be worn when handling or treating all primates, especially macaques. Anti-viral treatment should be initiated immediately if contact with bodily fluids through an open wound, mucous membranes or by accidental inoculation (e.g. needle stick; bite wound, etc.) occurs.

There are a number of viruses carried by one species of primate that can cause fatal disease in another species of primate, including Herpesvirus platyrrhinae, carried by squirrel monkeys, fatal in owl monkeys and callitrichids - hepatitis and necrosis of multiple body organs; herpes simplex carried by humans, fatal in several species of New World Primates (e.g. owl monkeys); Herpesvirus saimiri carried by squirrel monkeys, causes lymphoproliferative diseases in owl monkeys, marmosets, spider monkeys, howler monkeys and cebus monkeys; Herpesvirus Ateles, carried by spider monkeys, causes lymphoproliferative disease in owl monkeys and marmosets. Mixed species exhibits need to be carefully considered and the mixing of African and Asian species are generally avoided. Encephalomyocarditis virus has been reported in variety of primates and non-primates. The classic signs are a nonsuppurative necrotizing encephalitis and myocarditis. Rodents are thought to be natural reservoir and vector control is important to prevent the disease. LCMV (lymphocytic choriomeningitis virus) causes callitrichid hepatitis and is an acute, highly fatal disease and is associated with the feeding of infected neonatal mice.

Toxoplasma gondii is primarily a problem in New World primates and lemurs (rare in apes). Infection is through the ingestion of oocysts (cat feces or other items contaminated with cat feces) or ingestion of raw meat containing cysts (e.g. primates catching feral rodents). Oocysts can also be transmitted by cockroaches. Sudden death is common. Vector control is important in preventing this disease.

Diarrhea is a common medical problem of primates with a variety of etiologies: bacterial (Shigella, Salmonella, Campylobacter, Yersinia, and E. coli), parasitic (amoeba, nematodes, cestodes), viral, and dietary / environmental. Try to make a specific diagnosis prior to treatment.

Tuberculosis is rarely diagnosed these days, and is not a natural primate disease, but rather one that primates catch from man (a disease of captivity). Any primate is susceptible, though Asian old world monkeys are most susceptible (especially rhesus macaques). Typically extensive pulmonary granulomatous lesions and marked lymphadenopathy are seen. Intradermal testing with mammalian tuberculin, (human isolates) is the most commonly used screening test, but it is a poor test for individuals. Radiographs, culture (tracheal wash, gastric lavage, and rectal swabs), and blood tests (Prima-gam, TB stat pak) are other diagnostics to use. False positives and false negatives are a problem. Treatment tends to suppress, but not cure, the disease.

Type 2 diabetes mellitus is the most common form of diabetes seen in non-human primates, though parasite-induced diabetes mellitus has been reported in New World primates. Insulin resistance occurs in obese humans and may be the earliest metabolic abnormality detected as impaired glucose tolerance develops prior to the onset of diabetes. It is likely to be similar in non-human primates. The simplified pathophysiology is insulin resistance develops causing compensatory hyperinsulinemia, normal glucose tolerance is then lost and more and more insulin is required to effectively keep blood glucose levels normal. A state of a relative or absolute reduction in insulin secretion is then reached, due to pancreatic exhaustion (normal pancreatic architecture is replaced with islet-associated amyloid). Diagnosis is by measuring chronic hyperglycemia. Other causes of hyperglycemia need to evaluated (hyperadrenocorticism, iatrogenic corticosteroids, glucagonoma, pheochromocytoma, chronic hepatic disease). Urinalysis and fructosamine, glycosylated hemoglobin, and insulin levels are used to confirm the diagnosis. Glucose tolerance tests are infrequently used. Treatment of diabetes in primates includes oral antihyperglycemics (e.g. glipizide, acarbose, pioglitazone), insulin (e.g. premixed isophane insulin and regular insulin, glargine), dietary / weight management (restrict overall caloric intake, balance fat, protein, and carbohydrates, increase dietary fiber), and exercise.

Endometriosis is a condition in which the endometrium grows in other areas of the body, causing pain, irregular bleeding, and frequently infertility. The tissue growth typically occurs in the pelvic area, outside of the uterus, on the ovaries, bowel, rectum, bladder, and the delicate lining of the pelvis, but it can occur in other areas of the body as well. Typically seen in Old World primates (New Worlds don't menstruate). The cause of endometriosis is unknown. Once the endometrial cells implant in tissue outside of the uterus, they may become a problem. During the estrous cycle estrogens stimulate the uterine endometrium as well as the endometrial cells outside of the uterus. However these cells lack the ability to then separate themselves from the surrounding tissue and slough off during the next menstrual period. They sometimes bleed a little bit, but they heal and are stimulated again during the next cycle. Ovarian blood cysts have been known to grow to the size of a hen's egg or even an orange, and are usually painful. Over time the collected blood darkens and, for this reason, the cysts are frequently called "chocolate cysts." Gonadotropin agonists, such as leuprolide acetate (Depo Lupron), prevent stimulation of the pituitary for the production of follicle stimulating hormone and luteinizing hormone and this stops the ovary from producing estrogen. Bilateral ovariectomy is recommended where future breeding is not required.

Preventive Medicine

Routine examinations should be performed annually or as needed based on the animal's age, health status, or other factors. Recommendations include a physical exam, dental exam (including radiographs and prophylaxis), CBC, chemical profile, periodic viral serology, fecal culture for enteric bacterial pathogens, fecal screening for ova and parasites, urinalysis, TB intradermal test, and chest and abdominal radiographs.

Vaccination recommendations vary by species. Tetanus toxoid is recommended for all species and rabies vaccination should be considered where exposure risk is high. Diphtheria Pertussis Tetanus (DPT) and Measles Mumps Rubella (MMR), and Polio vaccine should be considered for apes. Vaccination schedules for great apes can be based on recommendations made by the American Academy of Pediatrics.

Suggested Resources

1.  Bennett et al. (eds.) 1998. Nonhuman Primates in Biomedical Research: Diseases. Academic Press, San Diego, California.

2.  Nutrient Requirement of Non-Human Primates. 2nd edition. The National Academies Press, Washington D.C.

3.  Primate chapters. 2003. In: Fowler M. E. and R. E. Miller. (Eds.) Zoo and Wild Animal Medicine. 5th edition. Saunders, St. Louis, Missouri. Pp. 334-397.

4.  Primate chapters. 2007. In: West, et al. (Eds.) Zoo Animal and Wildlife Immobilization and Anesthesia. Blackwell Publishing, Ames, Iowa. Pp. 367-394.

5.  Veterinary Information Network (https://www.vin.com).

Speaker Information
(click the speaker's name to view other papers and abstracts submitted by this speaker)

Geoffrey W. Pye, BVSc, MSc, DACZM
Zoological Society of San Diego
San Diego Zoo
San Diego, CA, USA

Consultant
Veterinary Information Network


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