Introduction
Longevity records for captive exotic animals are being set all the time at zoos and private exotic animal collections throughout the world. This has been due to numerous factors, including attention to diet, exercise, mental health and enrichment. The standard of care for many facilities now includes recording daily observations of health and well being, routine preventative medical procedures, weight monitoring, and regularly scheduled complete physical examinations. While this is a testament to advancements in veterinary medicine and animal husbandry, it means veterinarians should practice a more evidence based medicine, especially when dealing with geriatric animals. Captive non-human primates (NHP) are a prime example of what exemplary medical care and advanced husbandry can do to increase animals' life spans in captive situations. Many of these animals far outlive their wild counterparts. Geriatric NHP, like other geriatric animals, will have their own set of health problems that need to be addressed. Physical examinations on geriatric NHP should include examinations of eyes, teeth, musculoskeletal system, endocrine, neurologic, cardiovascular, renal, reproductive, and gastrointestinal systems.
Discussion
Ocular and Dental Issues
As animals age, close inspection of their eyes for age related changes should be done. Changes such as cataract formation, glaucoma, iris atrophy and macular degeneration commonly occur in animals and some of these changes may be painful. Also remember if animals have compromised vision, their social status, if housed in a group, may be affected.
Dental issues can often cause concern in geriatric NHP. Many of these animals can be trained to have their teeth brushed on a daily basis and complete dental examinations and treatments should be done opportunistically when animals are placed under anesthesia. Periodontal disease may need to be managed over long periods of time as NHP age. Therapeutic courses of broad spectrum antibiotics can be used acutely. Maintenance low dose therapy doxycycline at 0.3 mg/kg twice a day for 90 days, then stop for 90 days, then start cycle again etc. has been used successfully for resolution of disease.3
Musculoskeletal System
One of the most commonly seen problems in geriatric non-human primates is diseases of joints. Like in the elderly human population, long-term wear and tear on the joints can result in osteoarthritis, or degenerative joint disease. Clinical signs seen in these animals include decreased activity and range of motion, weight loss, signs of pain such as bruxism, and joint swelling. Diagnosis is made by a thorough physical examination, radiographs, and joint palpations. When a geriatric NHP is placed under general anesthesia for examination, it is always helpful to remember proper placement of the limbs. Improperly positioning arthritic joints and not supporting limbs in these animals can cause pain and decreased movement in recovery that sometimes can last for several weeks.
Once the diagnosis of arthritis is made, treatments may vary according to location of joints affected, age of the animal, concurrent health issues, and severity of pain. Treatments may involve options like physical therapy (often done with the aid of a physical therapist and operant conditioning), weight control, dietary supplements that target affected joints, and exercise. Looking at the environment the animal is housed in and modifying it to meet the needs of the aged animal may help lessen the onset and severity of arthritis. Areas of specific concern that warrant attention may be areas where the animal has to jump and/or climb, hard floors, drafty areas, and areas where the animal may be forced to move in unnatural ways.
Medications may be used to try to reduce inflammation and joint damage. Starting with drugs that have the least number of side effects is often warranted. As the condition progresses, stronger medications may be needed. The first drug of choice is usually over the counter non-steroidal anti-inflammatory drugs (NSAIDS). If these medications do not work, stronger painkillers such as Tramadol®, a µ- receptor opiate agonist (PriCara, Division of Ortho-McNeil-Janssen Pharmaceuticals, Inc. Raritan, New Jersey, USA 08869) may be used. There are no published dose ranges for Tramadol® in NHP, but at Zoo Atlanta, we have successfully used it for pain control in apes and large NHP at doses of 0.2–3 mg/kg BW twice a day to effect, not to exceed total doses of 400 mg/day. Celecoxib (Celebrex ®) is a highly selective COX-2 inhibitor. Dosing for NHP at Zoo Atlanta has been successful at dosage ranges of 0.6 – 3 mg/kg BW. There are reports of using gabapentin, a gamma-aminobutyric acid-mimetic compound (Neurontin® Parke-Davis, Pfizer, New York, NY 10017, USA) as an additional analgesic for refractory pain in NHP. Doses should be titrated based on positive response. Humans can go on doses up to 3600 mg/day and veterinary doses in NHP have been around 3–5 mg/kg once to twice a day.1 Research into concurrent health issues, pharmacokinetic and pharmacodynamic changes associated with aging needs to be done before placing animals on these drugs to avoid potentially harmful side effects.9 As with any medication, the lowest effective dose should be used. Corticosteroids may be given in cases of acute pain, however due to their potential side effects, should only be used acutely, not for long term pain control.
Endocrine System
Non-human primates can develop any number of endocrine disorders as they age. Some of the more common disorders seen include endocrine neoplasia, diabetes and thyroid disorders. Endocrine neoplasia has been documented in both new world (NWP) and old world NHP (OWP). In NWP, the most commonly affected organ in one zoo collection was the adrenal gland (53.5% of cases), followed by the pituitary and thyroid (15.4% each), and pancreas and parathyroid glands with 7.7%.6
Diabetes is also seen in many collections. Causes of diabetes in NHP vary from obesity and poor diet, genetic predisposition, gestational diabetes, and toxin/infectious disease exposures. Determination of what type of diabetes will aid in appropriate treatment courses. Laboratory tests should include a complete blood count (CBC), a blood chemistry (Chem) including blood glucose, insulin levels, fructosamine, glycosylated hemoglobin and a urinalysis. Many of these animals can be trained through operant conditioning to give urine and blood daily.12,14,17 They may also be trained to receive daily insulin shots if needed. Dietary changes that restrict overall caloric intake while balancing the amounts of fat, protein and carbohydrates and increasing fiber intake may be difficult due to animal and owner compliance in these animals but are very important. The decision of whether to use oral antihyperglycemics and what type will depend on the levels of circulating insulin, and the type of diabetes diagnosed. Some oral antihyperglycemics are dependent on circulating levels of insulin for their mechanism of action, so if the animal is hypoinsulinemic, response to therapy will be poor. If insulin therapy is indicated, trying to get the animal onto once a day treatment with longer acting insulin is preferable.15
Hypothyroidism is another endocrine disorder that may affect older NHP. Clinical signs include weight gain, dry skin, hair loss, and hypothermia.13 Laboratory testing should include a CBC, chem., including cholesterol levels, and a urinalysis. If hypothyroidism is suspected, a complete assessment of thyroid function is also indicated. Measurement of basal T4 concentration should be viewed as a screening test. A T4 concentration that is well within the normal range should rule out hypothyroidism. If T4 is low, other diagnostic tests are needed. Measuring free T4 (to determine the amount of active thyroid hormone) with total T4 may help to reduce false positive diagnoses. Thyroxin supplementation can be of help in cases were hypothyroidism is suspected. A positive response to therapy should include improved attitude, weight loss, and hair regrowth. If a positive response to therapy is noted, the animal should be placed on lifelong supplementation with scheduled monitoring. Levothyroxine, a synthetic form of thyroxin hormone available in many forms, is the initial therapy of choice and following recommended doses for humans is recommended.
Nervous System
Neurological diseases, predominately neoplasia and trauma, may also occur in geriatric NHP. It is important to get a complete health assessment of the animal in order to rule out other potential diseases that may present as a neurological problem such a hepatic encephalopathies, otitis, infectious causes, drug reactions, diabetic ketoacidosis, and cardiomyopathies. A complete neurological examination may be difficult to perform on an awake NHP so visual observation and a complete diagnostic workup under anesthesia may be the only options for assessment.
Cardiovascular System
Cardiovascular disease is a well documented problem seen in geriatric NHP.2,7,18 Documented causes referenced in great apes include fibrosing cardiomyopathy, atherosclerosis, aortic aneurysms, dilated cardiomyopathy, and congestive heart failure.7 Diagnosis is based on complete physical examinations and blood work, as well as echocardiograms and EKGs. The need for established echocardiographic normal values for many of these species can make diagnoses challenging. Many NHP will not present with signs of cardiac problems until the disease is at an advanced stage. Clinical signs at that time may include exercise intolerance, anorexia, dyspnea, abdominal swelling, and edema. Transient ischemic events may also occur and present as animals with hemiparesis, lip droops, and somnolence. Some NHP will die acutely from presumptive acute arrhythmias without any premonitory clinical signs. It is important, therefore, to include a complete cardiac examination during any medical examination of a geriatric NHP. Treatments used have included beta blockers and ACE inhibitors, diuretics, positive inotropes, dietary modification, salt reduction and weight loss.
Renal Disease
As NHP age, renal disease may occur.5 Reports of high incidences of glomerulonephritis in callitrichids should place this high on rule out lists when seeing these small primates.8,10 Like in other disease process, a complete medical evaluation is needed to determine the type and extent of renal disease present. Clinical signs depend on the extent of lesions but typically signs of uremia are present. Chronic renal failure (CRF) may occur and is defined as primary renal failure that has prevailed for a lengthy period, usually months to years. As in other animals with CRF, laboratory evaluation will typically show an increase in blood urea nitrogen, creatinine, hyperphosphatemia, metabolic acidosis, and a nonregenerative anemia. The urine specific gravity is usually in the isosthenuric range (1.007 to 1.015). Radiographs will often show small kidneys with irregularities. Treatment of CRF is intended to maximize renal function while slowing disease progression and relieving uremia. Correcting electrolyte and fluid imbalances, treating possible bacterial infections, hypertension, and addressing nutritional status will all help to improve the animal's renal status, as well as quality of life. These animals usually require initial treatment with intravenous fluids for at least 24 to 72 hours, but such intensive fluid therapy may not be easy in NHP without restraint. In addition, symptomatic treatment of gastrointestinal signs with H2 receptor blockers to reduce gastric hydrochloric acid production may be warranted. Traditional dietary therapy used in domestic animal medicine is very difficult in NHP. Many of these species have specialized nutritional needs, so careful consideration and research into providing daily protein, calorie, vitamin and mineral requirements needs to be done before limiting their diets.
Reproductive Disorders
Reproductive disorders are also of concern in geriatric NHP. These may include neoplasia, infections, and inflammatory problems. Because many of these animals remain sexually intact but reproductively non-active, problems tend to occur later in life. Uterine and ovarian cancers, uterine fibroids, and endometriosis may all be issues of older NHP.4 Clinical signs observed have varied from no clinical signs to draining tracts, swollen abdomens and genitalia, and abnormal menstruations. A complete physical examination, blood work, radiography and abdominal ultrasounds should be performed on geriatric, intact female NHP. Treatment may consist of surgical removal of the reproductive organs. Surgery can be complicated due to the frequency and severity of endometriosis and adhesions in many of these animals. Consulting human gynecological surgeons is often a wise decision in these cases. Male NHP tend to have decreased fertility and sperm quality.11 Reproductive neoplasia can also affect males.
Gastrointestinal Disorders
Gastrointestinal disorders are frequently seen in all ages of NHP. Intestinal cancer appears to be the most common malignant neoplasm seen in NHP and is a significant cause of morbidity and mortality in geriatric NHP.16 Clinical presentations include weight loss, anorexia, diarrhea, emesis, bloating, decreased stool production and anemia. Surgical resection is the treatment of choice with adjunct therapies as indicated. In a multi-institutional retrospective study, gastrointestinal neoplasia among macaques accounted for 13% of all tumors and often was malignant.16 In contrast, gastrointestinal tract tumors were infrequent and generally benign among other Old World monkeys, including baboons, colobines, and guenons. The incidence of malignant neoplasia substantially increased in nonhuman primates over 20 years of age: 27% in baboons, 6.5% in macaques, and 12% in green monkeys. The prevalence of colonic cancer also increased progressively with age, reaching a peak of 20.7% in macaques over 30 years of age.16 Other possible gastrointestinal conditions that should be considered are intestinal leiomyomas, leiomyosarcomas, adenomatous polyps, lymphoma, and carcinoid tumors.
Conclusion
Due to advancements in veterinary medicine and animal husbandry, many NHP are now living to old age. Becoming familiar with what diseases and chronic age changes may affect the animals as they age is critical to ensure continued care for these geriatric patients. The veterinarian plays a critical role in management of geriatric health issues, including issues of pain-control, control of suffering, and quality of life in many of these animals. Owners of NHP tend to look on these animals as more than just "pets" so it can be up to the veterinarian to guard against keeping a suffering animal alive for too long. Clients may need to be counseled and euthanasia decisions can be extremely difficult in these cases
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