Bacterial Diseases of Nonhuman Primates
The bacteria most commonly associated with GI disease in nonhuman primates are Campylobacter jejuni and Shigella spp. Occasionally, enterotoxigenic Escherichia coli, Pseudomonas aeruginosa, Yersinia spp, Lawsonia intracellularis, Salmonella spp, Aerobacter aerogenes, and Aerobacter hydrophila are implicated. Nonhuman primates may be intermittent, asymptomatic carriers of any of these organisms. Helicobacter spp have been implicated as a cause of gastritis, anorexia, and vomiting.
GI diseases may be major problems in captive nonhuman primates. Clinical signs include watery or mucoid, blood-tinged feces, rapid dehydration, emaciation, and prostration. Smaller primates will dehydrate and become hypoglycemic very rapidly. In many privately owned nonhuman primates, dietary indiscretion is common, and the owner should be asked about irregular feeding habits. Rectal prolapse is an occasional sequela. Helminths or pathogenic protozoa may be a complicating factor. Fecal assays and trichrome stains should be done, and appropriate anthelmintics administered. Mortality can be extremely high in acute outbreaks unless treatment is instituted promptly to restore and maintain normal fluid and electrolyte balance. The most common lesions at necropsy are hemorrhagic enteritis, enterocolitis, colonic ulcers, or simply colitis.
Severe clinical signs and death are generally due to dehydration, hypokalemia, and metabolic acidosis. Hydration should be restored and maintained with parenteral electrolyte solutions. Although medications may often be easily administered parenterally, potassium, B vitamins, electrolytes, bismuth subsalicylate, and antibacterial agents can be administered PO or by nasogastric tube in most nonhuman primates. Culture and identification of the infecting organisms and assessment of antibiotic sensitivity may be needed for effective therapy. Metronidazole at 25–50 mg/kg, PO, bid, may be instituted until culture results are obtained. Enrofloxacin (5 mg/kg/day) or the combination of trimethoprim (4 mg/kg) and sulfamethoxazole (20 mg/kg), administered as a total daily oral dosage for 10 days, is useful to treat shigellosis. Azithromycin (30–50 mg/kg, IM, bid for 7–14 days) is recommended to treat Campylobacter-associated diarrhea.
Upper respiratory diseases of bacterial origin can cause widespread illness, and bacterial pneumonia is associated with increased mortality, particularly in newly imported or immature nonhuman primates. Causative agents include Streptococcus pneumoniae, Klebsiella pneumoniae, Bordetella bronchiseptica, Haemophilus influenzae, and various species of streptococci, staphylococci, and pasteurellae. Both New World and Old World infant primates are highly susceptible to cross-species transfer from people. Many times, caretakers have had a history of an upper respiratory infection, so adequate history on presentation is important. Infants that are handreared frequently present with aspiration pneumonia from bottle feeding, and appropriate cultures and radiographs will be needed.
Pneumonia may accompany or follow other primary diseases (eg, dysentery or respiratory viral infection). Clinical signs may include coughing, sneezing, dyspnea, mucoid or mucopurulent nasal discharge, pyrexia, lethargy, anorexia, and weight loss. The principal lesions seen at necropsy are those of bronchopneumonia or lobar pneumonia. Empiric antibiotic therapy with azithromycin, trimethoprim/sulfamethoxazole, penicillin, or cephalosporin (either of the latter two in combination with an aminoglycoside) generally is indicated. Cultures from pharyngeal swabs or transtracheal lavage are useful to isolate the causative agent and determine the specific antibiotic sensitivity. Intensive nursing and other supportive therapy, such as fluid and oxygen administration, may also aid recovery in select cases.
All nonhuman primates are susceptible to tuberculosis, although major differences exist in the prevalence of cases in different species. Most cases of tuberculosis in nonhuman primates have been reported in Old World primate species such as rhesus monkeys. Reports in New World species such as squirrel monkeys are much less frequent. The incidence of tuberculosis is <1% among quarantined Old World primates, but 45% of cases (especially cynomolgus monkeys) may not be diagnosed until after the first 30 days of quarantine. Clinical signs are not a reliable indication of the severity of tuberculosis in monkeys. A monkey that appears healthy may have extensive miliary disease involving thoracic and abdominal organs; signs of debilitation may appear only shortly before death. However, advanced tuberculosis should be suspected in animals that cough; lose appetite or weight; and/or have enlarged or draining lymph nodes, skin wounds that fail to heal, or abdominal masses. A testing program is mandatory; a tuberculin skin test (intradermal tuberculin skin test), using mammalian old tuberculin (MOT) is the only USDA-approved tuberculin test for nonhuman primates and is the primary diagnostic method for routine surveillance. Intradermal injection of 0.1 mL of MOT using a 26-gauge needle in the palpebrae is an approved USDA method; 0.5 mL may be used in marmosets and tamarins. The injection sites are observed at 24, 48, and 72 hr after injection. Grading systems can be found in the Guidelines for the Prevention and Control of Tuberculosis in Nonhuman Primates at http://oacu.od.nih.gov/ARAC/documents/NHP_TB_Prevention.pdf. If palpebral swelling is present with a lid droop, this may be interpreted as positive. Tuberculin tests should be done on all nonhuman primates on arrival at the facility and at 2-wk intervals thereafter until at least three consecutive negative tests have been recorded for the entire group. The last test should be administered within 14 days of the release from quarantine and introduction into an established colony.
The time from initial infection to skin-test conversion depends on the route of exposure, the infecting inoculum, and the strain of organism, but usually occurs within 3–4 wk in rhesus monkeys. Late in the disease, anergy can result in a negative skin test. Anergy may also be induced by concurrent viral infection, such as measles, or immunosuppressive disease. Infected nonhuman primates may also develop latent tuberculosis. These animals appear healthy, are not infectious, and are often skin-test negative. Latent tuberculosis may be reactivated in response to environmental stressors or other immune modulation, leading to active disease and potential transmission.
After their release from quarantine, all nonhuman primates should be skin-tested at least semiannually, and quarterly testing is recommended for research animals. Captive animals in private settings and New World primates may be tested annually. Radiographic examination of the chest may aid diagnosis in well-established cases but is unreliable because lesions rarely calcify or cavitate as they do in people. Additional diagnostic tests, such as culture, PCR, and staining of a gastric lavage or transtracheal wash sample, ELISA, and comparative abdominal skin testing with avian and atypical tuberculins, may aid in diagnosis. Biopsies of positive or suspicious abdominal tests may be useful in identifying true delayed-type hypersensitivity reactions. Because of the public health risk, euthanasia is recommended for all positive reactors. Tuberculosis should then be confirmed at necropsy. When a positive case is identified, the entire group of exposed nonhuman primates in a maintenance colony should be quarantined, and skin testing at 2-wk intervals implemented. Privately owned animals should be quarantined away from small children and untrained personnel. For animals in quarantine, the period should be restarted and testing should be continued. All personnel working with any nonhuman primates or in primate facilities should have regular skin tests.