All surgical procedures and drugs used should be recorded and kept in the animal’s file. Post-operative notes should be kept until the animal is fully active and is eating and drinking normally. Anesthetics and analgesics should be used in consultation with an institution’s veterinarian as doses vary by nonhuman primate species. Animals should be examined and any pre-existing conditions (i.e., liver or kidney problems, bleeding disorders, high blood pressure, or diabetes) should be discussed with the veterinarians before drugs are administered. Experienced veterinary staff should be available to monitor nonhuman primates under anesthesia, and emergency drug kits should always be accessible. Specific anesthesia and analgesia protocols acceptable for use in nonhuman primates have been reviewed in detail [155-158].

Scheduled Drugs

The Drug Enforcement Agency has categorized all prescription drugs with potential for abuse by whether they have accepted medical uses and their likelihood for psychological or physical dependence (on a scale of I to V, where I includes illegal narcotics that have no medical applicability). Records must be kept for all schedule II and III (and any experimental schedule I) [159].

Fasting Nonhuman Primates

Primates should be fasted prior to the administration of anesthetics to avoid the regurgitation of stomach contents and subsequent aspiration into the lungs. Larger primates can be fasted 12 hours (overnight) prior to a procedure, but smaller primates should only be fasted six to eight hours, as they can become hypoglycemic [22]. It is unnecessary to withhold water.

Preanesthetic Medications

Preanesthetics can be useful in calming an animal for handling and anesthetic induction, making anesthesia safer, and for diminishing the need for anesthesia. Low doses of anti-cholinergics such as atropine and glycopyrrolate can be used as positive chronotropes and can prevent an animal’s heart from slowing under anesthesia as well as reducing the amount of bronchial and salivary secretions [1]. Tranquilizers provide muscle relaxation without analgesia or major sedation.

Inhaled Anesthetics

Inhaled anesthetics are preferable for longer procedures as they are easily regulated, provide supportive oxygen, and tend to have more rapid recovery times. However, inhaled anesthetics require precise systems to vaporize the liquid anesthetic and mix it with the (typically) oxygen gas vehicle, and these machines are somewhat expensive [1,155]. Consult a veterinarian regarding the use of anesthesia on pregnant animals.

Anesthetic Emergencies

In the event of cardiac arrest, follow the "ABC’s" of airway, breathing, cardiovascular support, of Cardio Pulmonary Resuscitation (CPR). Establish a patent airway by intubating the animal if that has not been done in order to administer the anesthesia. Be sure to turn off any inhalant anesthesia agent, and ventilate the animal with 100% oxygen at a rate of one breath every five seconds. Next, begin administering heart compressions, at least one per second, and no need to coordinate with ventilation. Also begin administering intravenous fluids. In the event that no heartbeat is heard or pulses felt, then epinephrine can be administered intravenously. If spontaneous respiration is absent, doxapram HCl (Dopram®) may be given as a stimulant. Alternately, a 22 to 28 gauge, one to 1.5 inch needle can be placed in the nasal philtrum at the ventral limit of the nares. The needle is twirled and moved up and down while the animal is monitored for an improvement in respiratory status. Reversal agents may also be administered if necessary. See the Drug Formulary (Appendix 1) for a list of drugs that should be kept immediately available in an emergency drug kit [22].

Analgesia for Nonhuman Primates

Conscious nonhuman primates typically attempt to mask signs of pain, so handlers familiar with their behavior are most likely to detect any slight changes in their behavior. An animal may have a decreased interest in its environment or food, it may be favoring a painful area, or there may be a region of obvious redness, swelling, or pyogenesis. It is possible for nonhuman primates to experience pain while they are under anesthesia as well. This can be assessed by noting an increase or decrease in respiration, body temperature, or blood pressure; an increase in heart rate; and changes in levels of circulating cortisol and catecholamines [1].

There are two categories of analgesics used to control pain in nonhuman primates: nonsteroidal anti-inflammatory drugs (NSAIDs) and opioids. Aspirin is the most common NSAID, but it is most effective on muscle pain and is only minimally effective on visceral pain. Ketorolac tromethamine provides relief from slightly stronger postoperative pain; its advantage over opioids being a lack of sedation or cardiopulmonary depression. However, it may prolong bleeding and thus should not be used in animals with coagulopathies [155,159].

Oxymorphone is the opioid of choice for use in nonhuman primates, as it produces little respiratory depression, while still providing significant pain relief. Buprenorphine and butorphanol (opioid agonist-antagonists) are longer lasting options for pain relief with little respiratory depression or sedation reported, but larger doses can result in marked respiratory depression without additional analgesia. Naloxone is a useful opioid antagonist that can be used to reverse respiratory depression that is a result of opioid treatment. It is short acting, so two doses may be necessary [155]. See the Drug Formulary for dosage information and consult a veterinarian for more information regarding analgesia.

Euthanasia of Nonhuman Primates

Each institution using nonhuman primates should establish its own particular guidelines and criteria for euthanasia. It is considered unacceptable and inhumane to simply wait for death as an experimental endpoint or if disease befalls an animal. Euthanasia and necropsy should be performed to end any disease-associated pain, and to find the cause of disease.

Criteria for Euthanasia

Animals exhibiting signs of end-stage illness should be euthanized to bring a conclusion to any pain or distress. Animals showing signs of inappetance (50% reduction in caloric intake for seven days in larger species or complete anorexia for up to five days) or rapid loss of body weight (20%) and emaciation should be given strong consideration for euthanasia. Additionally, an animal that is unable to remain upright or is weak, unconscious, or impaired to the point of being unable to reach food or water for extended periods should be considered to be exhibiting signs of end-stage illness. Euthanasia should be a consideration for any animal that is suffering from systemic symptoms of an infection (as indicated by elevated body temperature or skewed CBC numbers) that is unresponsive to antibiotics within a reasonable amount of time. An institution’s veterinarian can determine the extent of organ system damage and whether euthanasia is appropriate [160,161].

Methods of Euthanasia

Refer to the 2000 AVMA Guidelines On Euthanasia [162].

Diseases and Medicine

Viral Diseases of Nonhuman Primates

Adenovirus

Infectious agent: Family: Adenoviridae; Mastadenovirus: Mastadenovirus tree shrew adenovirus 1, several simian and chimpanzee serotypes of Mastadenovirus human adenovirus strains.

Mode of transmission: Aerosol.

Disease characteristics: This disease can be asymptomatic. Clinical signs can present as conjunctivitis, respiratory infections, and diarrhea. Pancreatitis has been noted in rhesus monkeys. Severe infections can develop in immunodeficient animals. Pathology is often seen in immunodeficient monkeys, including necrotizing alveolitis and bronchiolitis, pneumonia, necrotizing pancreatitis, and enteritis (intranuclear inclusion bodies).

Diagnosis: Virus isolation and serology. Viral species can be differentiated by DNA on agarose gels, oncogenicity, and G-C% hemagglutination patterns [163].

Treatment: Supportive therapy.

Prevention: Quarantine new animals, minimize overcrowding, provide good sanitation [164].

Benign Epidermal Monkey Pox (poxvirus) - zoonotic

Infectious agent: Family: Poxviridae, Subfamily: Chordopoxvirinae; Yatapoxvirus.

Incubation: Four to five days [164].

Mode of transmission: The definitive host and vector(s) are not yet known.

Disease characteristics: This disease affects both humans and macaques. Clinical presentation includes the appearance of multiple crusted maculae on face and extremities, which heal in approximately three to eight weeks [2]. Pathological findings include epidermal hyperplasia, ballooning degeneration, and necrosis. Affected cells show flask-shaped proliferative nodules of epidermal cells that can have both intracytoplasmic and intranuclear inclusion bodies.

Diagnosis: Serology.

Treatment: No treatment available.

Prevention: Previous infection with Tanapox is protective from subsequent viral challenge [164-167].

Callitrichid Hepatitis (Lymphocytic Choriomeningitis)

Infectious agent: Family: Arenaviridae; Lymphocytic choriomeningitis virus (LCMV-various strains).

Mode of transmission: Ingestion (feeding Callitrichids neonatal mice), mouse urine, or oral secretions.

Disease characteristics: Disease affects Callitrichidae species (tamarins and marmosets).

Clinical signs include generalized weakness and anorexia, respiratory distress, and death. Pathological findings include jaundice, subcutaneous and intramuscular hemorrhage, hepatosplenomegaly, and pleuropericardial effusions are seen grossly. Histopathology findings include meningitis, encephalitis, gliosis, necrosis in the spleen and lymph nodes, and interstitial pneumonia [164,168-170].

Diagnosis: Virus isolation and serology. Blood chemistries can show elevations in liver enzymes, bilirubin, and alkaline phosphatase.

Treatment: Supportive therapy.

Prevention: Screening of food source rodent colonies for LCMV. Rodent control in primate housing areas [2,164].

Cytomegalovirus

Infectious agent: Family: Herpesviridae, Subfamily: Betaherpesvirinae. Despite a narrow host range, interspecies transmission does occur.

Mode of transmission: Horizontal: virus is shed in urine, saliva, blood, milk, and semen.

Disease characteristics: Latent infection. Disease is produced only in fetuses and immunodeficient individuals. Pathological findings in immunodeficient animals include generalized infections with necrotizing meningitis and neuritis, interstitial pneumonia, arteritis, enterocolitis, orchitis, and focal necrosis of the liver and spleen. The disease has a unique pattern of intranuclear inclusion bodies (Cowdry-type A) and granular eosinophilic cytoplasmic inclusion bodies [164,171-173]. Immunodeficient infected humans are treated with gancyclovir [162].

Diagnosis: Tissue and shell-vial culture can be used to detect infection, as can polymerase chain reaction (PCR) of cerebrospinal fluid. If results correlate with findings from tissue culture, PCR on other tissue is acceptable [174]. In situ hybridization may be useful when only mild cytomegaly is present by histological methods [164].

Treatment: Active cytomegalovirus infection is typically seen only in immunocompromised individuals, thus as a first line of attack against infection, if possible, immunosuppressive therapy should be discontinued. Antiviral therapy is typically indicated with active infection as well. In humans, intravenous ganciclovir is the antiviral of choice, followed by foscarnet and cidofovir [174]. Lifetime maintenance of antivirals in immunocompromised individuals may be necessary due to reactivation of infection after therapy is discontinued.

Prevention: Avoid contact with infected animal tissues. Good husbandry and sanitation practices.

Dengue (Flavivirus)

Infectious agent: Family: Flaviviridae; single-stranded RNA virus.

Mode of transmission: Arthropod (mosquito) vector: Aedes aegypti and Aedes alobopictus.

Disease characteristics: Causes human hemorrhagic fever in sub-tropical and tropical regions of the world. The significance of Dengue in free-ranging wild nonhuman primate populations is unknown. However, these same nonhuman primate populations have a high rate of seroreactivity to the virus confirming widespread exposure. No clinical disease seen in affected nonhuman primates [2,164,175-177].

Diagnosis: Serology, virus isolation.

Prevention: Mosquito abatement in endemic areas and effective quarantine programs.

Ebola And Marburg Virus - zoonotic

Infectious agent: Order: Mononegavirales, Family: Filoviridae; Zaire ebolavirus, Sudan ebolavirus, Tai Forest ebolavirus (formerly Ivory Coast ebolavirus), Reston ebolavirus [178]; Lake Victoria marburgvirus [179].

Incubation Period: Two to 14 days in nonhuman primates.

Mode of transmission: Direct contact with blood and body fluids. Aerosol transmission has also been documented in non-human primates.

Disease characteristics: Zoonotic. Report disease to Centers for Disease Control and Prevention (CDC). Maculopapular rash, splenomegaly, widespread petechial hemorrhages, proximal duodenum hemorrhage, and interstitial pneumonia are seen. Other symptoms include: lymphoid necrosis, massive fibrin deposition in the spleen, hepatic necrosis, interstitial nephritis, and necrosis of the adrenal cortex and pulmonary bronchiolar and alveolar epithelium. Diagnostic triad: interstitial pneumonia, hepatocellular necrosis, and necrosis of the zona glomerulosa of the adrenal cortex.

Diagnosis: Serology, radioimmunoassay [180].

Treatment: Affected animals should be euthanized [2,164,181-187]. Any exposed personnel should be isolated and medically evaluated immediately.

Encephalomyocarditis Virus

Infectious agent: Family: Picornaviridae; Cardiovirus: Encephalomyocarditis virus (various strains).

Mode of transmission: Oral. Rodents are reservoir hosts.

Disease characteristics: Spontaneous death. This disease can cause myocarditis in nonhuman primates, pigs, elephants, and some other species. Pathology findings can include myofibril necrosis with inflammation and edema. Secondary lesions are typically characteristic of acute heart failure. Extensive myocardial scarring occurs in animals that survive acute infection [164,188].

Diagnosis: Virus isolation. Must differentiate from coxsackie virus toxoplasmosis, and trypanosomiasis [164,189-192].

Prevention: Good sanitation and the elimination of rodent reservoir host.

Hepatitis A - zoonotic

Infectious agent: Family: Picornaviridae; Hepatovirus: Simian hepatitis A virus (various strains); RNA virus [193].

Mode of transmission: Fecal-oral.

Disease characteristics: Zoonotic. Infects humans, chimpanzees, marmosets, owl monkeys, macaques, and African green monkeys. Seroconversion and elevation of transaminases are usually the only clinical evidence of infection. Some hepatitis A virus (HAV) isolates may be unique to nonhuman primates. Gross lesions can include hepatomegaly, splenomegaly, jaundice, subcutaneous and intramuscular lesions, and pericardial effusions. Periportal and parenchymal mononuclear inflammation, slight focal hepatocellular degeneration, necrosis with acidophilic bodies, and Kupffer cell hyperplasia have been documented [2,169,194-197].

Diagnosis: Virus isolation, serology, elevated serum alanine aminotransferase and aspartate aminotransferase (two to ten times above reported normals), and mild elevations in bilirubin are characteristic of the disease [2].

Treatment: In most nonhuman primates, infection is usually self-limiting. Previous infection with HAV is protective [164]. Two vaccines, Havrix (SmithKline Beecham) and VAQTA (Merck), are available.

Hepatitis B - zoonotic

Infectious agent: Family: Hepadnaviridae; Orthohepadnavirus; enveloped DNA virus [164].

Incubation period: Prolonged

Mode of transmission: Blood, saliva, semen, parenteral inoculation; direct contact required.

Disease characteristics: Zoonotic. Hepatitis B virus (HBV) has been detected in chimpanzees, gorillas, and less frequently in cynomolgus macaques [164,198-203]. Usually there are no clinical signs other than seroconversion and elevated transaminases. Chronic periportal inflammation with focal hepatocyte necrosis has been noted. Chronic HBV infection is associated with a significantly increased risk for chronic active hepatitis and hepatocellular carcinoma [164].

Diagnosis: Serology.

Treatment: Effective vaccines are still being developed [201].

Hepatitis C

Infectious agent: Family: Flaviviridae; Hepacivirus: Hepatitis C virus (various types and isolates); single-stranded, double-shelled, enveloped RNA virus.

Mode of transmission: Blood, blood products, and body fluids.

Disease characteristics: The chimpanzee and humans are susceptible [204,205]. Chimpanzees have been experimentally infected, however spontaneous infection in nonhuman primates has not been reported. Hepatitis C virus infection (HCV) in humans is a slow, asymptomatic progressive disease that can lead to hepatic cirrhosis and the development of hepatocellular carcinoma [196,206,207].

Diagnosis: Enzyme immunoassay (EIA) is the recommended initial test. Serology, PCR, and recombinant immunoblot assay (RIBA) [206].

Treatment: None developed for nonhuman primates. Multiple therapeutic approaches applied in humans.

Prevention: Avoid contact with infected body fluids and blood or blood products from affected animals.

Hepatitis E

Infectious agent: Family: Caliciviridae; Calicivirus; single-stranded, non-enveloped RNA.

Mode of transmission: Spread through water sources contaminated with feces (fecal-oral) [193].

Disease characteristics: Experimental inoculation, a number of species appear susceptible (owl monkeys, cynomolgus monkeys, rhesus macaques, mustached tamarins, African green monkeys, and chimpanzees. Cynomolgus monkeys appear to be the most susceptible to experimental inoculation. Causes a mild nonsuppurative portal hepatitis. Virus is shed in feces through bile [2,193].

Diagnosis: Virus isolation and serology.

Treatment: None identified at this time.

Prevention: Proper sanitation.

Herpes B Virus - zoonotic

Infectious agent: Family: Herpesviridae, Subfamily: Alphaherpesvirinae; Simplexvirus: Cercopithecine herpesvirus 1, Herpesvirus simiae.

Mode of transmission: Aerosol, bite wounds, mucous membranes, scratches, venereal exposure, or human-human.

Disease characteristics: Zoonotic. Self-limiting disease in primates; is rarely fatal in natural host (macaques). Latent virus persists in trigeminal and sacral sensory nerve root ganglia [208]. Clinical signs in macaques include vesicles and ulcers in the oral cavity and conjunctivitis. Humans may exhibit vesicles at the site of bite or scratch, and a disseminated viral infection resulting in ascending paralysis, encephalitis and likely death.

Diagnosis: Virus isolation by PCR, reverse transcription-polymerase chain reaction (RT-PCR), or enzyme-linked immunosorbent assay (ELISA). Serology and viral cultures should be sent to the National B Virus Resource Center, Viral Immunology Center, Georgia State University, 50 Decatur Street, Atlanta, GA 30303. Information on submission can be obtained from the B Virus Research and Resource Laboratory, Georgia State University, P.O. Box 4118, Atlanta, Georgia 30302-4118, Phone: 404-651-0808 (Emergency: 404-358-8168), Email: [email protected], web address: http://www.gsu.edu/bvirus.

Treatment: Consult Center for Disease Control and Prevention (Dr. Louisa Chapman, 404-639-3747). Follow bite/scratch protocol. If treating your aggressive anti-viral therapy is indicated post exposure. There are currently three antiviral agents available for the treatment of B virus infection, though these drugs have not been approved by the US Food and Drug Administration for the treatment of herpes B virus [209].

Primates are not treated for herpes B virus. However, they must be diagnosed by techniques mentioned above. In the event off human exposure, immediately refer to the Centers of Disease Control and Prevention Guidelines for the Herpes B exposure.http://www.gsu.edu/bvirus

Prevention: Personnel should assume that all macaques are infected with and are capable of periodically shedding the virus. Periodic serological screening of all macaques can aid in viral detection.

Herpesvirus Papio 2

Infectious agent: Family: Herpesviridae, Subfamily: Alphaherpesvirinae; Simplexvirus: Cercopithecine herpesvirus 2, related to Herpesvirus simiae and SA8.

Mode of transmission: Venereal, oral, endemic in baboons.

Disease characteristics: The virus may persist latently within the sensory ganglia. Recrudescence can occur periodically and is often associated with environmental stresses [210]. Oral, genital, and cutaneous vesicular, papillomatous, or ulcerative lesions can be seen in baboons. Inguinal lymphadenopathy has also been noted [211].

Diagnosis: Viral isolation, serology.

Herpesvirus Saimiri

Infectious agent: Family: Herpesviridae, Subfamily: Gammaherpesvirinae; Rhadinovirus: Saimiriine herpesvirus 2.

Mode of transmission: Oral.

Disease characteristics: Squirrel monkeys are the natural host of this disease. However, this disease causes lymphomas in marmosets, African green monkeys, owl monkeys, spider monkeys, and howler monkeys. Clinical signs include lymphadenopathy, hepatomegaly, splenomegaly, and leukemia. Pathological findings in affected primate species include leukemic infiltrates of immature lymphocytes, occurring in multiple organ systems (liver, kidney, spleen, lymph nodes, and adrenal glands). Focal necrosis in affected organs can also be demonstrated. There are no pathological lesions noted in squirrel monkeys despite a lifelong latent infection in T-cells [164].

Diagnosis: Viral isolation and serology.

Prevention: House squirrel monkeys separately from susceptible primate species.

Herpesvirus Simplex - zoonotic

Infectious agent: Family: Herpesviridae, Subfamily: Alphaherpesvirinae; Simplexvirus: Herpesvirus simplex.

Mode of transmission: Direct contact; human to monkey, monkey to monkey, or latent infection. Humans are the natural reservoir of this disease.

Disease characteristics: Oral vesicles, conjunctivitis, encephalitis, and death. Owl monkey (Aotus sp.), tree shrew (Tupaia glis), marmosets, and tamarins (Saguinus sp.) are susceptible to generalized disease. Chimpanzees (Pan sp.) and gibbons (Hylobates lar) can be infected, but infection usually remains confined to skin, oral cavity, external genitalia, and conjunctiva. Pathological findings include necrotizing meningoencephalitis, and focal necrosis in visceral organs [188].

Diagnosis: Virus isolation and serology.

Prevention: Personal protective equipment (PPE) for humans. Modified live vaccine has been developed for owl monkeys [164,212-217].

Herpesvirus Tamarinus

Infectious agent: Family: Herpesviridae, Subfamily: Alphaherpesvirinae; Herpesvirus saimiri 1, Marmoset herpesvirus, Herpesvirus M, Herpesvirus tamarinus, Saimiriine herpesvirus 1, Squirrel monkey alphaherpesvirus type 1.

Incubation period: Seven to ten days.

Disease characteristics: Squirrel monkeys are the natural host of this disease and have a high incidence of natural infection. Clinical signs include oral vesicles or ulcers similar to Herpes simplex in humans and Herpes simiae in macaque species. Herpes T produces a generalized disease in owl monkeys and marmosets characterized by a vesicular rash and oral vesicles and ulcers [218]. Occasional syncytial cells and eosinophilic intranuclear inclusion bodies [188]. Susceptible species like tamarins, owl monkeys, and marmosets can result in high morbidity and mortality. Clinical signs in affected species include pruritus, anorexia, and death within 24 to 48 hours [164].

Mode of transmission: Oral

Diagnosis: Virus isolation and serology.

Treatment: A live vaccine is available.

Prevention: Squirrel monkeys should be housed separate from susceptible species [219-221].

Lymphocryptovirus

Infectious agent: Family: Herpesviridae, Subfamily: Gammaherpesvirinae; Lymphocryptovirus 1 and 2, various animal species.

Mode of transmission: Direct contact, oral secretions.

Disease characteristics: Lymphocryptovirus and acute fatal lymphoproliferative disease in marmosets. Clinical signs include weight loss, inappetance, diarrhea, and abdominal masses. Infected monkeys are seropositive for Epstein Barr Virus. The virus infects B lymphocytes and persists for life. Identification can be by pathology findings, lymphoproliferative disease, lymphosarcoma [222].

Diagnosis: Virus isolation, PCR, and serology.

Measles (Rubeola Virus) - zoonotic

Infectious agent: Family: Paramyxoviridae; Morbillivirus: rubeola virus.

Mode of transmission: Respiratory, direct contact.

Disease characteristics: Zoonotic [223]. The disease may be sub-clinical or may consist of a maculopapular rash, conjunctivitis, facial erythema, respiratory difficulty, and diarrhea. Pathological findings include focal necrosis of the oral mucosa, maculopapular rash to vesicular rash, intestinal pneumonia, and gastroenterocolitis. Syncytial cells with both intracytoplasmic and intranuclear inclusion bodies can be demonstrated [188]. Clinical disease can be self-limiting and ranges from upper respiratory disease to pneumonia. Affected primate populations have high morbidity and low mortality [2]. Measles virus is immunosuppressive which can result in a false-negative tuberculin skin test [164].

Diagnosis: Serology

Treatment: Clinical disease is usually self-limiting. Epizootics in macaques have been controlled by human γ-globulin therapy combined with modified-live vaccine administration [223].

Prevention: Vaccination with a modified-live vaccine has proven effective in both New World and Old World nonhuman primates [224-227].

Molluscum Contagiosum (Molluscipoxvirus)

Infectious agent: Family: Poxviridae, Subfamily: Chordopoxvirinae; Molluscipoxvirus: Molluscum contagiosum.

Mode of transmission: Direct contact.

Disease characteristics: Clinical signs include waxy, umbilicated epithelial papules, three to eight millimeters in diameter that present on the skin (eyelids, inguinal region) in humans and chimpanzee. Affected cells show flask-shaped proliferative nodules of epidermal cells that can have both intracytoplasmic and intranuclear inclusion bodies. Marked acanthosis with large intracytoplasmic inclusion bodies that become more prominent towards the skin surface [188].

Diagnosis: Virus isolation [2,164,228].

Monkeypox (Poxvirus) - zoonotic

Infectious agent: Family: Poxviridae, Subfamily: Chordopoxvirinae; Orthopoxvirus: Callithrix jacchus orthopoxvirus, Monkeypox virus(various strains); it is immunologically related to smallpox and vaccinia.

Mode of transmission: Old World monkeys, New World monkeys, and apes are susceptible. Aerosol, direct contact, and by biting insects [229].

Disease characteristics: Zoonotic [230]. Usually nonfatal in nonhuman primates. One to four millimeter diameter cutaneous papules that develop into pustules which crust over, drop off, and leave scars. Pathology findings show hyperplasia and necrosis of the epidermis, swelling of keratinocytes and large eosinophilic intracytoplasmic inclusions point to monkeypox. Visceral lesions can occur [218]. Additional information on monkeypox can be accessed via the Centers for Disease Control and Prevention website (http://www.cdc.gov/ncidod/monkeypox/). Diagnosis: Virus isolation and serology.

Treatment: Usually self-limiting. Supportive therapy may limit mortality in severe systemic disease.

Prevention: Vaccination against smallpox provides immunity to monkeypox in most cases [164].

Papillomavirus

Infectious agent: Family: Papillomaviridae; Papillomavirus.

Mode of transmission: Direct contact, fomites, and sexual transmission.

Disease characteristics: Disease presents as papillomas that appear on the skin and oral/genital mucosa. Pathological findings include focal hyperkeratosis and acanthosis. Histologically, massive hyperplasia of the stratum spinosum and corneum are noted.

Diagnosis: Papillomavirus antigens can be demonstrated by immunohistochemistry (IHC) and virions by transmission electron microscopy (TEM) [188,231].

Treatment: No treatment is available at this time.

Prevention: Formalin-inactivated autologous vaccines have been utilized in other species but their efficacy has not been determined [164].

Rhesus Lymphocryptovirus, Epstein-barr-like Viruses (EBV) - zoonotic

Infectious agent: Family: Herpesviridae, Subfamily: Gammaherpesvirinae; Lymphocryptovirus: nonhuman primate EBV-related Gammaherpesviruses, Herpesvirus Macaca fascicularis-1 (HVMF-1) in Macaca fascicularis.

Mode of transmission: Direct contact.

Disease characteristics: "Zoonotic". Generally occurs as a latent infection. In immunodeficient animals, lymphocryptoviruses have been associated with lymphoma and with squamous epithelial proliferative lesions on the skin and mucous membranes. Pathological lesions include focal squamous cell proliferations resembling oral hairy leukoplakia on oral, genital, and cutaneous surfaces in immunodeficient animals. Old World species of nonhuman primates are commonly asymptomatic carriers [164].

Diagnosis: Virus isolation and serology.

Simian Hemorrhagic Fever Virus

Infectious agent: Order: Nidovirales, Family: Arteriviridae; Arterivirus: Simian hemorrhagic fever virus. Incubation period: Three to seven days.

Mode of transmission: Parenteral exposure to blood or body fluids, direct contact, or aerosol. Endemic in some wild Patas monkeys (Erythrocebus patas) and possibly other African species (African green monkeys, baboons) that remain in a persistently viremic state. Animals can be viremic without antibodies.

Disease characteristics: Report disease to Centers for Disease Control and Prevention (CDC). Explosive epizootic with nearly 100% mortality in macaques. Clinical signs in macaques include fever, anorexia, depression, facial edema, epistaxis, and cutaneous and subcutaneous hemorrhage. Elevated aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase can occur at the onset of disease. Also, disseminated intravascular coagulation, and thrombocytopenia are usually documented with SHF. Pathological findings may not be present in early stages of the disease. Late disease state pathology: petechial hemorrhage of the mucosal and serosal surfaces. Hepatic necrosis without the presence of Councilman’s bodies (necrotic hepatocytes develop a distinctive intracytoplasmic hyaline change) [2,188,232-238].

Diagnosis: Cell culture, electron microscopy, and histopathology [239].

Treatment: No treatment available at this time. Multifaceted approach recommended:

1) elimination of clinically ill or exposed animals, 2) quarantine of remaining animals, 3) disinfection of premises, 4) diagnostics to identify etiologic agent, 5) notification of appropriate government agencies, and 6) monitoring of human contacts [239,240].

Prevention: Prevent the exposure of African primates and macaques to blood and tissue products. Keep host primate species separate [164].

Simian Varicella Virus

Infectious agent: Simian varicella virus (SVV, Cercopithecid herpesvirus) is a category of closely related herpesviruses including Deltaherpesvirus, Medical Lake macaque virus, Liverpool vervet monkey virus, and others. All are antigenically related to human varicella-zoster [218].

Mode of transmission: Respiratory.

Disease characteristics: Herpetic rash, depression, or respiratory difficulty is commonly noted. Pathological findings include vesicles on skin, oral mucous membranes, and esophagus. Intranuclear inclusion bodies Cowdry-type A are found in tissue layers adjacent to vesicles. Focal necrosis in the lungs, liver, spleen, lymph nodes, adrenal glands, bone marrow, and intestinal tract has been noted. Virus becomes latent in trigeminal ganglia [164].

Diagnosis: Virus isolation, PCR, and serology.

Treatment: Acyclovir and interferon have been efficacious in some experimental models [241-250].

Simian Virus 40 (SV40) - zoonotic

Infectious agent: Family: Polyomaviridae, Polyomavirus: Rhesus macaque polyomavirus, SV40. Mode of transmission: Direct contact; shed in urine.

Disease characteristics: Widespread, latent infection; most cases are sub-clinical. Clinical signs of SV40 can present as central nervous system and respiratory signs in immunocompromised animals. Pathological indications are usually absent. In immunocompromised animals, interstitial pneumonia, renal tubular necrosis, encephalitis, and demyelination progressive multifocal leukoencephalopathy (PML) have been observed. This is a natural virus infection of rhesus monkeys [188].

Diagnosis: Electron microscopy (EM), in situ hybridization [164,251-254].

Yaba Pox Virus - zoonotic

Infectious agent: Family: Poxviridae Subfamily: Chordopoxvirinae; Yatapoxvirus: Yaba virus, Yaba monkey tumor virus.

Mode of transmission: Arthropod (mosquito) vector.

Disease characteristics: Zoonotic. Natural infections occur in humans, rhesus, and baboons. Disease is marked by the onset of rapidly growing subcutaneous nodules up to four centimeters in diameter that appear on the head and extremities. These nodular lesions spontaneously slough and heal approximately six to 12 weeks after onset [188]. Pathology of this disease is unique due to the fact that Yaba pox affects histiocytes and not epithelial cells, unlike other pox viruses. Yaba pox induces the subcutaneous proliferation of histiocytes (eosinophilic cytoplasmic inclusions)

Diagnosis: Histology, virus isolation [164].

Yellow Fever- zoonotic

Infectious agent: Family: Flaviviridae, Flavivirus: Yellow fever virus (various strains).

Mode of transmission: Arthropod (mosquito) vector: Aedes aegypti in urban areas, Aedes africanus and Aedes simpsoni in Old World sylvatic areas, Haemogogus sp. in New World sylvatic regions [153].

Disease characteristics: "Zoonotic". In primates, a short viremic stage is characteristic. The virus invades the liver and is harbored in hepatocytes and Kupffer cells. Viral infection subsequently depletes vitamin K-dependent clotting factors leading to coagulopathies [164]. Histologically, lesions in the liver are characterized by multifocal midzonal hepatocellular necrosis with the Councilman bodies and Torres bodies noted [255].

Diagnosis: Serology, virus isolation, PCR, ELISA, immunofluorescent antibody (IFA), hemagglutination inhibition, complement fixation (CF), and histopathology [2,153,154,164].

Treatment: Supportive therapy.

Prevention: Mosquito abatement in endemic areas [2,154]. A vaccine is available for use in humans.

Primate Retroviruses

Retroviruses - general information [256-258].

Retroviruses are enveloped, RNA-containing viruses that replicate by reverse transcription of the RNA into DNA, which persists in the infected cell either chromosomally integrated or in episomal form. The retrovirus family is divided into 4 subfamilies:

Spumaviruses (foamy viruses) - The least well characterized of all the retroviruses. At least fourteen types have been isolated in non-human primates [259]. Zoonotic, however, probably not pathogenic [260,261].
Lentiviruses (slow viruses, SIVs) - cause chronic debilitating diseases after long latency periods. All lentiviruses have characteristic morphogenesis and morphology which distinguish them from the other retrovirus groups.
Type C oncornaviruses - the most widely distributed retrovirus subfamily in nature. Infection is commonly associated with lymphoproliferative and other malignant disorders. Pathogenicity is particularly pronounced in young animals.
Type D retroviruses - Type D simian retroviruses are not closely related to the human AIDS agents. None of the type D viruses have any genomic or antigenic relationship to HIV or SIV [262].

Primate Lentiviruses

Simian Immunodeficiency Virus (SIV)

Infectious agent: Family: Retroviridae, Subfamily: Lentivirinae [2] Mode of transmission: Horizontal (bite wounds), dam to infant (nursing), and sexual contact [2,263,264].

Disease characteristics: All forms of SIV are morphologically identical, and serologically and biologically very closely related to one another. Their morphology is very similar to that of the human immunodeficiency viruses (HIV-1 and HIV-2). Affected animals are predisposed to a host of opportunistic infections [164]. The virus infects T-helper (T4) cells, not T8 cells, therefore decreased T4:T8levels are observed. Microscopic lesions of lymphatic tissues include normal tissue, follicular hyperplasia, follicular involution with normal or expanded paracortical regions, depletion of follicular and paracortical regions, granulomatous lymphadenitis and generalized lymphoproliferative syndrome [164].

Diagnosis: virus isolation, PCR.

Prevention: Serial testing and removal of positive reactors is a successful method to eliminate the virus from a closed primate population [2,164,170]. Selected references in detail concerning nonhuman primate retroviral diseases [52,164,256,259-262,264-343].

Simian Type C Oncornaviruses

Simian T-Cell Leukemia Virus (STLV-1)

Infectious agent: Family: Retroviridae, Subfamily: Oncovirinae, Group: Type C. Mode of transmission: Parenteral inoculation, sexual contact, vertically transmitted. Exogenous virus is horizontally transmitted.

Disease characteristics: Latent infection. It has been reported in baboons, macaques, owl monkeys, colobus monkeys, and howler monkeys. Clinical signs include depression, anorexia, lymphadenopathy, and hepatosplenomegaly [2,344]. Affected nonhuman primates can be clinically normal with development of humoral antibodies or with persistent viremia in the absence of a detectable humoral response. Finally, nonhuman primates can develop hematopoietic malignancies (classified as either lymphocytic leukemia/lymphoma or chronic granulocytic leukemia). STLV has been associated with lymphoma/leukemia in baboons. STLV-1 infects CD+ T cells in macaques and CD8+ T cells in African monkeys [170].

Diagnosis: Serology, ELISA, PCR, virus isolation.

Simian Type-D Retroviruses

Infectious agent: Family: Retroviridae, Subfamily: Oncovirinae, Type D.

Mode of transmission: Horizontal transmission, persistently isolated from lymph nodes, saliva, and milk [316].

Disease characteristics: Endogenous and exogenous retroviruses. Type D subfamily currently consists of 5 serotypes: SRV-1, SRV-2, SRV-3 (MPMV), SRV-4 and SRV-5. SRV-4 is closely related antigenically to SRV-1 to 3. SRV-5 from Chinese macaques needs to be tested separately. The virus produces an immunosuppressive disease in macaques which may be epizootic in previously naïve populations. Affected animals may develop lymphadenopathy, splenomegaly, severe neutropenia, lymphopenia, recurrent diarrhea, weight loss, and opportunistic infections, while maintaining normal T4:T8 levels. Noma is a severe, rapidly progressing necrotizing gingivitis/stomatitis. It has been observed in 6 rhesus with spontaneous SAIDS and SRV-1 viremia at the California Primate Research Center [2,289].

Diagnosis: ELISA, PCR, and Western Blot [335,345].

Prevention: Screening of primates using a combined virus isolation and antibody determination protocol [164,170,275,346].

Bacterial Diseases of Nonhuman Primates

Bordetella

Infectious agent: Bordetella bronchiseptica.

Bacterial classification: Gram-negative, pleomorphic, coccobacilli.

Disease characteristics: Mucopurulent nasal discharge, dyspnea, and death have been noted. Pathological findings include fibrinopurulent hemorrhagic bronchopneumonia.

Mode of transmission: Respiratory, commensal.

Diagnosis: Isolation from clinical swabs (B. bronchiseptica can be cultured on blood and MacConkey agars at 37°), and histopathology.

Treatment: Antibiotic therapy (chloramphenicol, oxytetracycline, amoxicillin, amikacin, and kanamycin), autogenous bacterin [2,347-351]. Prevention: Elimination of shipping stress, overcrowding, poor environmental conditions [348].

Campylobacter - zoonotic

Infectious agent: Campylobacter jejuni, C. coli, C. fetus.

Bacterial classification: Gram-negative, curved, motile, S-shaped microaerophilic bacteria.

Mode of transmission: Fecal-oral.

Disease characteristics: Zoonotic. Primates showing clinical signs of this disease may include bloody diarrhea and dehydration. There also is a report describing four monkeys in which chronic gastritis associated with a Campylobacter-like organism was an incidental finding [352]. Asymptomatic carriers of this disease are common [353].

Diagnosis: Bacterial isolation of organisms using Skirrows media with 5 - 7% lysed horse blood. Plates must be incubated at 42° C in 5 - 10% oxygen, 5 - 10% C02 environment for 3 - 4 days. Serial serum samples can be tested by ELISA to detect increasing antibody titer [154,351].

Treatment: Erythromycin is the antibiotic of choice (30 - 50 mg/kg, PO, x7 days) [354]. Infected animals can serve as carriers post treatment. Aggressive fluid therapy (balanced electrolyte solution) can be used to correct any fluid deficits.

Prevention: Good sanitation and hygiene practices [352,355-369].

Escherichia coli

Infectious agent: Escherichia coli.

Bacterial classification: Gram-negative, rod, ubiquitous aerobic to facultatively anaerobic.

Mode of transmission: Fecal-oral route.

Disease characteristics: Pneumonia, meningitis, acute inflammation of the colon, and diarrhea. Fibrinopurulent pneumonia and serositis, pyelonephritis, hemorrhagic gastroenteritis [188,370,371]. Recently, enteropathogenic Escherichia coli (EPEC) has been isolated from rhesus monkeys infected with simian immunodeficiency virus [288].

Diagnosis: Culture, PCR, and histology.

Treatment: Ampicillin, gentamicin, or trimethoprim-sulfamethoxazole antibiotics. Gastrointestinal protectants combined with supportive therapy [2,349].

Prevention: Good sanitation practices.

Helicobacter

Infectious agent: Helicobacter pylori.

Bacterial classification: Gram-negative, spiral or curved, flagellated bacterium.

Mode of transmission: Oral.

Disease characteristics: This disease usually has no clinical presentation. Pathological signs include mononuclear inflammatory cell infiltrates in the lamina propria of the stomach, superficial erosions, and epithelial hyperplasia may be noted.

Diagnosis: Giemsa or silver stains will readily demonstrate the curved, rod-shaped, gull-wing, or loosely coiled organism associated with the gastric epithelium. Samples acquired by biopsy are preferred for culture techniques. Helicobacter pylori is urease positive, therefore a rapid urease test can be used [170].

Treatment: Antibiotic therapy is recommended (amoxicillin, metronidazole, and bismuth subsalicylate) [2].

Prevention: Good sanitation and hygiene practices.

Klebsiella

Infectious agent: Klebsiella pneumoniae.

Bacterial classification: Gram-negative, aerobic, nonmotile rod-shaped, encapsulated bacterium.

Mode of transmission: Respiratory.

Disease characteristics: Fibrinopurulent pneumonia, serositis, airsacculitis, enteritis, and septicemia [2,170,372,373].

Diagnosis: Bacterial culture.

Treatment: Autogenous bacterin, tetracycline (55 mg/kg), oxytetracycline, amikacin [374,375].

Prevention: Decrease environmental stressors.

Leprosy

Infectious agent: Mycobacterium leprae.

Bacterial classification: Acid-fast (Mycobacterium), filamentous forms.

Mode of transmission: Respiratory; direct contact has not been ruled out.

Disease characteristics: Clinical presentation of the disease includes nodular thickening of the skin and peripheral nerves. Natural disease reported only in sooty mangabeys and a chimpanzee (disease in sooty mangabeys proposed as model of human disease). It is a chronic progressing disease which produces granulomatous lesions proliferating in the cooler peripheral areas of the primate (ears, face, extremities) [376-388]. Histiocytic infiltrate with variable numbers of lymphocytes and plasma cells in skin and nerves. Nerve lesions are pathognomonic.

Diagnosis: Lepromin skin test, and histopathology (Acid-fast bacilli demonstrable with Fite-Faraco acid fast stain) [387,389].

Treatment: Rifampin (10 mg/kg body weight/day orally for 1 month), rifampin (20 mg intramuscularly every 77 days), rifampin (600 mg daily), dapsone (100 mg daily), and clofazimine (100 mg daily) for 6 months, and supportive therapy [2,351,387,390].

Prevention: Quarantine new animals.

Listeria

Infectious agent: Listeria monocytogenes.

Bacterial classification: Gram-positive, nonspore-forming pleomorphic coccobacillus, motile, peritrichous flagella.

Mode of transmission: Oral, transplacental.

Disease characteristics: Infection can cause abortion, intrauterine death, neonatal sepsis, and meningoencephalitis occurs in infants. The mother acts as a carrier. Pathological findings include purulent meningoencephalitis, purulent placental villitis, intrauterine pneumonia, focal necrosis of liver and other organs [188].

Diagnosis: Clinical history of reproductive failure, histopathology.

Treatment: Antibiotics have not proven effective [351,391,392].

Moraxella catarrhalis

Infectious agent: Moraxella catarrhalis.

Bacterial classification: Gram-positive, oxidase-positive, catalase-positive [2].

Mode of transmission: Aerosol.

Disease characteristics: Commonly referred to as bloody nose syndrome in cynomolgus macaques. Clinical signs include epistaxis and periorbital edema. Pathological findings include mucohemorrhagic rhinitis [393-395].

Diagnosis: Bacterial culture, diplococcal organisms demonstrated in nasal cytological preparations. Differential diagnosis for epistaxis in macaque species includes simian hemorrhagic fever and Ebola arteriviruses [351].

Treatment: Long-acting penicillin [2,395].

Nocardia

Infectious agent: Nocardia asteroides.

Bacterial classification: Gram-positive, catalase-positive, aerobic, filamentous, branching, often beaded, and variably acid-fast.

Mode of transmission: Inhalation, oral. Organisms are common in soil and organic material.

Disease characteristics: Often associated with defects in cellular immunity. Clinical signs include dyspnea, epistaxis, chronic wasting, abdominal distension, chronic intermittent diarrhea, depression, and coma. Infections often occur predominantly in the lungs, but may disseminate. Mixed inflammatory infiltrates, disseminated abscesses, and granulomas are noted [2,188,351,396-399].

Diagnosis: Radiographs of pulmonary lesions cannot be distinguished from tuberculosis. Culture on blood agar and Sabouraud’s dextrose agar, incubate aerobically at 25° and 37° C. Tentative diagnosis of nocardiosis can be made by histopathology. Serologic testing has proven to be of uncertain sensitivity and is not readily available.

Treatment: No successful treatment identified [351]. However, possible treatments include trimethoprim sulfonamides and doxycycline. Resistant to fluoroquinolones.

Pseudomonas

Infectious agent: Pseudomonas aeruginosa, Pseudomonas pseudomallei.

Bacterial classification: Gram-negative, ubiquitous.

Mode of transmission: Environmental; P. aeruginosa is ubiquitous in moist environments worldwide. Pseudomonas pseudomallei is an environmental saprophyte in south east Asia.

Disease characteristics: Pseudomonas aeruginosa is an opportunistic pathogen that affects compromised animals. Common in primates immunosuppressed with steroids or whole body irradiation. Pseudomonas pseudomallei may infect animals and man in Southeast Asia and can remain clinically latent for years. The pathological hallmark of P. aeruginosa infection is a vasculitis without thrombosis. Bacilli are seen in the vessel wall. Pseudomonas pseudomallei (Melioidosis), infection can include serous nasal discharge, sneezing, pneumonia, abscesses, and granulomas [188,400-402].

Diagnosis: Clinical history, blood culture, and serology.

Treatment: Pseudomonas aeruginosa: Gentamicin (1.25 mg/kg, BID), plus procaine penicillin (50,000 units/kg BID, IM), plus polymyxin B(12,500 IU/kg, BID, IM) has proven effective [2,351,403,404]. Pseudomonas pseudomallei: This organism has been shown to be resistant to many antibiotics [405,406].

Yersinia

Infectious agent: Yersinia enterocolitica, Yersinia pseudotuberculosis.

Bacterial classification: Gram-negative, pleomorphic coccobacilli that is facultatively anaerobic.

Mode of transmission: Transmission is by fecal-oral route [407]. Wild birds and rodents are the reservoir host. Nonhuman primates are thought to be carriers of the disease.

Disease characteristics: Typically causes spontaneous death. Affected monkeys are often found dead but sometimes show diarrhea, depression, and dehydration. Abortions and stillbirths have been reported in primates affected with Yersinia pseudotuberculosis; however this has not been noted in Yersinia enterocolitica infections. Pathological findings include focal necrosis of liver and spleen, mesenteric lymphadenitis, ulcerative enteritis (classical triad of lesions) [196,408-410]. This disease has been reported in Rhesus macaques, baboons, squirrel monkeys, and other nonhuman primates.

Diagnosis: Fecal culture reveals large colonies of gram-negative bacteria in necrotic centers [188].

Treatment: Treatment is rarely successful. Chloramphenicol 100 mg/kg, divided doses TID [407]. Other treatment options include aminoglycosides, fluoroquinolones, and tetracyclines.

Prevention: Good hygiene and barrier methods of protection [407,408,410-420].

Salmonella - zoonotic

Infectious agent: Salmonella choleraesuis, S. choleraesuis arizonae, S. enteritidis, S. typhimurium.

Bacterial classification: Gram-negative, motile, facultative anaerobic bacteria.

Mode of transmission: Fecal-oral. Salmonella is most commonly transmitted by rodent feces.

Disease characteristics: Zoonotic. Infection more common than disease (carriers); disease is usually sporadic but can be epizootic. Like shigellosis but generally milder. Diarrhea of variable severity, usually without mucus and blood; can be fatal in severe cases. Pathological findings can include a necrotizing, suppurative enterocolitis. Salmonellosis can lead to bacterial septicemia resulting in pyogranulomas in the liver and other organs.

Diagnosis: Primary differential diagnosis for salmonellosis is shigella (no pathological involvement of small intestine, no septicemia). Diagnosis is by bacterial isolation of organisms with rectal swab, stool culture, or lesion (selenite broth at 37° C, primary cultures inoculated on blood, MacConkey, brilliant green, and Salmonella/Shigella agars for isolation and identification).

Treatment: Aggressive fluid therapy (balanced electrolyte solution) to correct any fluid deficits [2,154]. Antibiotic therapy is controversial, due to the possible development of resistant strains. Proponents of treatment recommend the aggressive use of fluoroquinolones.

Prevention: Protect colony and feed from vermin and infected staff. May be necessary to humanely eliminate carrier animals due to zoonotic potential [351,421-425].

Shigella - zoonotic

Infectious agent: Shigella flexneri, Shigella sonnei.

Bacterial classification: Gram-positive, nonmotile, aerobic, and facultative anaerobic bacteria [2].

Mode of transmission: Fecal-oral.

Disease characteristics: Zoonotic. Shigellosis is the most common enteric bacteria infecting nonhuman primates [188]. Clinical signs in primates carrying the disease can be precipitated by stress. This disease can be epizootic with high morbidity and mortality in susceptible populations, e.g., newly caught or imported animals. More severe disease is noted in young monkeys. Clinical signs include distended, red colon with thickened, edematous wall; catarrhal, suppurative, or fibrinonecrotizing mucosal exudate, mucosal hemorrhage; mucus, blood, flakes of exudate in liquid contents; enlarged, edematous, sometimes hemorrhagic mesenteric lymph nodes, congested mesenteric vessels. Microscopic: catarrhal to suppurative and necrotizing colitis, hemorrhage and edema of lamina propria and submucosa.

Diagnosis: Clinical signs with conformation of organism cultured on brilliant green agar.

Treatment: Aggressive antibiotic therapy in severe cases (enrofloxacin, amoxicillin) [154], aggressive fluid therapy (balanced electrolyte solution) to correct any fluid deficits [2].

Prevention: Good hygiene, proper housing and handling, isolation of affected primates. Treat with chloramphenicol and cephalosporin but do not expect to eliminate infection (carriers). Trimethoprim-sulfamethoxazole is a treatment and has been reported to eliminate carriers [426-435].

Staphylococcus

Infectious agent: Staphylococcus aureus.

Bacterial classification: Gram-positive, aerobic and facultative anaerobic, catalase positive, nonspore-forming, nonmotile.

Mode of transmission: Environment, common inhabitant of nose, upper respiratory system, and skin.

Disease characteristics: Commonly found in external wounds. Staphylococcus bacterium are often found at the site of pustular dermatitis, cellulitis, abscesses, fibrinous pericarditis, vegetative valvitis, thrombosis and infarction, and glomerulonephritis [2,188,351].

Diagnosis: Bacterial culture, blood culture.

Treatment: Antibiotic therapy; recommend culture and sensitivity testing due to prevalence of antibiotic-resistant strains [2]. In general, first generation cephalosporins are a good choice for these infections.

Prevention: Good sanitation, acute wound management.

Streptococcus pneumoniae

Infectious agent: Streptococcus (Diplococcus) pneumoniae.

Bacterial Classification: Gram positive, aerobic and facultative anaerobic, catalase negative chains, PYR hydrolysis negative, with growth in culture inhibited by optochin [208].

Mode of transmission: Respiratory.

Disease characteristics: Spontaneous death. Animals may exhibit signs of pneumonia, arthritis, depression, meningitis, or dehydration. Pathological findings noted include fibrinopurulent serositis affecting the meninges, pleura, peritoneum, and/or joints.

Diagnosis: Culture on a-hemolysis blood agar. Growth in cell culture is inhibited by optochin (ethylhydrocupreine hydrochloride). Diplococci are easily demonstrated on a gram-stained impression smear of exudates [188].

Treatment: Penicillin, 800,000 U/day and ampicillin 4 grams/day and diazepam 20 - 30 mg/day [436], or penicillin 20,000 U/day and ampicillin 200 - 400 mg/day and chloramphenicol 25 mg/kg TID [437], or ceftriaxone 50 - 100 mg/kg [2].

Prevention: Decrease stress related factors.

Tetanus

Infectious agent: Clostridium tetani.

Bacterial classification: Gram-positive, nonencapsulated, obligate anaerobe that produces spores that are highly present in the environment (soil, human and animal feces) [2].

Mode of transmission: Soil organisms contaminate open wounds and cause postpartum infections.

Disease characteristics: Clinical signs include progressive stiffness starting from the upper appendages and moving downward, inability to prehend food, abduction of pectoral limbs, stiff gait (bipedal running and hopping), trismus, opisthotonus, status epilepticus, extensor rigidity, and death within one to ten days of the onset of clinical symptoms [2,438-440].

Diagnosis: Clinical signs.

Treatment: 1500 units of veterinary tetanus antitoxin and supportive therapy (5 - 11 weeks),

Prevention: Immunization with tetanus toxoid with booster.

Tuberculosis (TB) (Mycobacterium) - zoonotic

Infectious agent: Mycobacterium tuberculosis, Mycobacterium bovis, Mycobacterium avium, Mycobacterium kansasii.

Bacterial classification: Acid-fast (Mycobacterium), filamentous forms; in gram stained sputum, M. tuberculosis appears as colorless rods or "ghosts," weakly gram-positive. Mycobacterium tuberculosis: produces niacin, lacks pigment, reduces nitrates, produces a small amount of catalase which is inactivated at 68°C at pH 7.0, and is usually isoniazid sensitive. Mycobacterium bovis and the other Mycobacteria are usually niacin-negative and do not reduce nitrates [208].

Incubation period: Variable in nonhuman primates, three to four weeks post-natural infection has been reported [52]. Positive intradermal tests have been observed as early as 12 days following experimental infection [441]. The incubation period in humans can range from two to 12 weeks [153,442]. Animals generally remain asymptomatic for weeks to months prior to showing the characteristic clinical signs.

Mode of transmission: Respiratory route, fecal-oral route, and direct transmission [351,443].

Disease characteristics: Zoonotic [153,154]. Old World nonhuman primate species are more susceptible to tuberculosis than New World nonhuman primates [52,443,444]. Tuberculosis in nonhuman primates is a progressive, highly aggressive disease. Clinical signs include sudden death, coughing, enlarged lymph nodes, chronic wasting, splenomegaly, and hepatomegaly. Gross pathology of animals affected with either M. tuberculosis or M. bovis can include the presence of disseminated granulomas (yellow-white in color) in the hilar lymph nodes and lung, large cavitary and coalescing lesions within the lung, and tubercles extending into the thoracic pleura. Occasionally tuberculous nodules may be found in the cerebrum, spinal column (Pott’s disease), omentum, uterus, ovary, peripheral lymph nodes, and skin [351]. Microscopic lesions are that of a typical granuloma with the central caseous necrosis surrounded by mononuclear inflammatory cells, and epithelioid cells. Occasional Langhans giant cells and mononuclear inflammatory cells are surrounded by a zone of connective tissue.

Diagnosis: Positive intradermal skin test. Because clinical signs are seldom present by themselves prior to terminal stages of the disease, radiographs are rarely diagnostic until late in the disease. Histological confirmation of acid-fast organisms taken from the core of granulomatous lesions can confirm diagnosis. Assays include culture (i.e. BACTEC System, Johnston Laboratories, Towson, MD) and isolation, computer-assisted gas-liquid chromatography, serology, EIA, PCR, and ELISA [208,445-449]. Another test, which uses p-nitro-alpha-acetylamino-beta-hydroxypropiophenone (NAP) to inhibit growth of members of the M. tuberculosis complex, is often used with the BACTEC System to determine whether or not the bacterium is a member of the complex. Sputum and tissue samples require liquefaction-decontamination to kill contaminating cells before culture can be conducted [208]. A commercially available ELISA kit (Primagam™) is marketed by Biocor Animal Health. A recent study performed by Garcia and colleagues at Stanford University recommended the parallel use of the whole blood Primagan assay with the intradermal test in order to diagnose Tuberculosis in primates [60]. Tuberculosis must be differentiated from nocardiosis, mycoses, lung mite lesions, Yersinia pseudotuberculosis, and other atypical mycobacteria. False positive test results can be obtained if the animal is infected with other atypical mycobacteria (eg. M. shenkii). Refer to Tuberculosis Test Administration and Interpretation (Clinical Methodologies) for further information. The tuberculin test can yield false negative tests depending on the animal’s immunological status and the interval between infection and testing.

Prevention: Intradermal skin testing programs [450-478]. Test and removal programs have been effectively used to control this disease in primate populations. Treatment: Isoniazid is a synthetic antibacterial compound which is regarded for having cidal activity of both intracellular and extracellular organisms; prophylaxis: 2.5 - 5 mg/kg/day; treatment: 10 - 25 mg/kg/day. Multi-drug regimens: Isoniazid (15 mg/kg/day), rifampin (22.5 mg/kg/day), and ethambutol (22.5 mg/kg/day) for six to 12 months PO resolved all lesions [456]. Streptomycin (40 mg/kg) and isoniazid (15 mg/kg) [477]. Isoniazid and p-aminosalicylic acid [2,479].

Protozoan Parasites of Nonhuman Primates

Amoeba - zoonotic

Infectious agent: Entamoeba histolytica and Balamuthia mandrillaris.

Mode of transmission: Oral.

Disease characteristics: Zoonotic. New World primates, Old World primates, and apes are commonly affected. Clinical signs can include diarrhea, however the majority of cases are asymptomatic. Pathological findings of amoebiasis include classical flask-shaped ulcers found in the intestinal mucosa, which can lead to a mild colitis. Trophozoite forms of the organism can be found in the mucosa and submucosa and occasionally the muscularis layer of the intestinal tract. Balamuthia mandrillaris, a free-living amoeba, has caused fatal meningoencephalitis in nonhuman primates [480-482].

Diagnosis: Periodic Acid Schiff (PAS) staining of affected tissue. Clinical signs, fecal exam, lesions.

Treatment: Metronidazole followed by treatments with iodoquinol, paromomycin sulfate, or diloxanide furoate [2,154,442].

Prevention: Good sanitation and hygiene.

Balantidium - zoonotic

Infectious agent: Balantidium coli.

Mode of transmission: Fecal-oral.

Disease characteristics: Zoonotic. Balantidium is usually non pathogenic but can occasionally cause diarrhea, ulcerative colitis, weight loss and lethargy in nonhuman primates [2]. This organism can be found in Old and New World monkeys and in apes. Balantidium is thought to be a primary pathogen in great apes and pigtail macaques (Macaca nemestrina), however it usually is found in combination with other pathogens in other nonhuman primate species [483-486]. The organism can commonly be located in the lumen of the colon in asymptomatic animals. Pathologic findings include ulcerative lesions and colitis.

Diagnosis: Examination of stool sample for trophozoites or cysts, histologic examination, autofluorescence microscopy of feces [154,487].

Treatment: Metronidazole (30 - 50 mg/kg/day divided doses TID), tetracycline (40 mg/kg PO divided dose TID), diiodohydroxyquin (40 mg/kg PO divided doses TID) [2,442]. Prevention: Good sanitation and hygiene.

Cryptosporidium - zoonotic

Infectious agent: Cryptosporidium sp.

Mode of transmission: Fecal-oral.

Disease characteristics: Zoonotic. Clinical disease occurs in young, sick, or immunocompromised animals. Diarrhea, weight loss and anorexia usually resolve spontaneously in normal animals, however the disease is untreatable in immunodeficient animals. Cryptosporidium is a common opportunistic infection in SRV and SIV-infected macaques. Pathological examination of intestines from affected nonhuman primates show organisms on the surface epithelium of intestinal villi. Villus atrophy and eosinophilic inflammation of the lamina propria are often associated with the presence of the organisms. Immunocompromised primates have characteristic eosinophilic inflammation of the conjunctiva, trachea, bronchioles, bile ducts, gallbladder, and the pancreatic duct. There is often marked bile duct hyperplasia of biliary and pancreatic duct epithelium and periductal fibrosis [294,488-492].

Diagnosis: ELISA, microscopic examination of oocyst in fecal smears using acid-fast procedure, and by histology [154].

Treatment: Supportive therapy and antibiotics [2].

Prevention: Good sanitation and hygiene.

Encephalitozoon

Infectious agent: Encephalitozoon cuniculi.

Mode of transmission: Oral, organism is shed in urine. Organism can be transferred transplacentally.

Disease characteristics: Disease can cause stillbirths and abortions in squirrel monkeys. Clinical signs may not be apparent. Pathologic lesions found in adults include focal microgranulomas in the brain and kidney. Lesions noted in infants and fetuses are disseminated granulomas in multiple organs (lung, aorta, liver, placenta, and other tissues) [493-496].

Diagnosis: Goodpasture’s staining of kidney/brain, gram staining of organisms in cyst, Giemsa staining, serology, ELISA, and IFA staining.

Prevention: Good sanitation and hygiene.

Treatment: None [2].

Giardia - zoonotic

Infectious agent: Giardia intestinalis.

Mode of transmission: Fecal-oral.

Disease characteristics: Zoonotic. Asymptomatic carriers are common. Giardia may be associated with self-limiting diarrhea and malabsorption. Giardiasis in immunocompromised primates is a serious opportunistic invader. Pathological examination of intestinal tissue demonstrates the organisms on the epithelial surface of the small intestine. The organisms are most commonly located in the mid-jejunum region [497].

Diagnosis: Saline wet mount of fresh fecal sample, isolation of cyst by zinc sulfate floatation technique [154].

Treatment: Metronidazole (30 - 50 mg/kg/day BID), furazolidone (1.5 mg/kg for seven days for marmosets) [2].

Prevention: Good sanitation and hygiene.

Hepatocystis

Infectious agent: Hepatocystis kochi and Hepatocystis simiae.

Mode of transmission: Transmitted by midges (Culicoides sp.).

Disease characteristics: Usually non pathogenic. Schizonts develop into very large (< four millimeter) megaloschizonts or merocysts; these grossly resemble miliary granulomas of TB. In hepatocystosis, schizogony occurs in the liver in nonhuman primates; therefore it produces no cyclic fever or waves of parasites in the blood as noted in malaria. Red cell forms resemble plasmodia. Gross lesions include numerous foci of grayish white areas on the liver surface which correspond to mature merocysts [2,498-501].

Diagnosis: Identification of parasites on thick blood smears, histologic lesions, and hepatic lesions on necropsy.

Treatment: Treatment with antimalarial agents have not proven effective to date [502,503]. Prevention: Vector control.

Malaria (Plasmodium)

Infectious agent: Plasmodium brazilianum, Plasmodium cynomolgi, Plasmodium gonderi, Plasmodium inui, Plasmodium knowlesi(several species have multiple strains).

Mode of transmission: Mosquitoes act as disease vector. The life cycle of malarial parasites is referenced in detail [504-508].

Disease characteristics: Old World monkeys, New World monkeys, and apes can become infected. Clinical signs are usually subclinical. Immunocompromised animals can exhibit clinical signs of jaundice, anorexia, listlessness, fever, anemia, splenomegaly, and death. The cyclic release of organisms for the host’s red blood cells (RBCs) is responsible for clinical signs. Malarial parasites can be classified by host infected, parasite morphology, or by the type of cyclic fever produced. Quotidian malarial fevers have a 24 hour cycle, tertian malaria has a 48 hour cycle, and quartan malaria has a 72 hour cycle [501]. Findings on pathological examination of affected animals include cloudy gray coloration of the lungs, liver, and spleen. Histological examination of tissue shows macrophages that are filled with malarial pigment, and hemosiderosis and parasitized RBCs. Intravascular clotting with thrombi and parasitized RBCs is a common finding. Often there is pulmonary and cerebral edema noted at necropsy [507-517].

Diagnosis: Thick blood smear; clinical signs, histology lesions, and serology (IFA).

Treatment: Chloroquine (2.5 - 5 mg/kg IM for four to seven days) for treatment against erythrocytic phase, followed by primaquine phosphate for treatment against hepatic phase (0.75 mg/kg PO for 14 days) [2,501].

Prevention: Mosquito control.

Malaria is referenced in detail [504-506,508,515,518-527].

Trypanosoma (Sleeping Sickness and Chaga’s Disease)

Infectious agent: Trypanosoma cruzi cruzi (Chagas disease) Trypanosoma brucei (Sleeping sickness) (multiple strains).

Life cycle: Trypanosomes undergo asexual reproduction in both the vector and the mammalian host; the trypomastigote is the blood form. When ingested by the intermediate host, the trypomastigotes multiply in the gastrointestinal tract, then as epimastigotes, in the salivary glands. The epimastigotes develop into infective trypomastigotes, which are injected into the mammalian host when the reduviid bug feeds on the host. The organisms multiply in the blood as trypomastigotes and in other tissues, such as heart muscle in the case of T. cruzi, as amastigotes [528-531].

Mode of transmission: Insect vector (Triatoma, reduviid "kissing bug"- (Chaga’s) and Tse-tse fly (sleeping sickness))

Disease characteristics: Animals may be asymptomatic or may show lymphadenopathy, hepatosplenomegaly, eyelid edema, heart failure, and sudden death. Examination of blood from affected animals demonstrates the trypanosomal forms. The most common pathological finding is an enlarged, mottled heart. Chronic myocarditis with cystic collections of leishmaniae in muscle cells is characteristic; both smooth and skeletal muscle can be affected [529-532].

Diagnosis: Blood or body fluid smear, histology, serology, EIA, and/or CF [2]. Differential diagnosis includes toxoplasmosis. Trypanosomes have a kinetoplast present.

Prevention: Screening test [533].

Treatment: In humans, the disease has been treated in its early stages with nifurtimox or benznidazole [534]. No treatment has proven effective at later stages.

Metazoan Parasites of Nonhuman Primates

Acanthocephala (thorny headed worms)

Infectious agent: Prosthenorchis elegans-located in both cecum and colon. Prosthenorchis spirula-located in the terminal ileum.

Mode of transmission: Ingestion of the intermediate host (cockroaches and beetles).

Disease characteristics: Historically this disease has been noted in marmosets and tamarins. Clinical signs include poor condition, intussusception and rectal prolapse on New World monkeys. Pathological findings include a granulomatous inflammation and nodule formation of the serosal surface of the intestinal tract due to adults burrowing and attaching to the intestinal wall. Adult worms can burrow through the intestinal walls, leading to perforation and subsequent peritonitis. Adult worms can also occur in great numbers and eventually lead to the mechanical blockage of the intestinal tract [535].

Diagnosis: Clinical signs, gross examination of parasites, and fecal smears [501].

Treatment: Oral carbon tetrachloride (0.5 ml/kg of body weight) [536-538]. Supportive therapy.

Prevention: Proper sanitation and vermin control.

Anatrichosoma

Infectious agent: Anatrichosoma cutaneum, Anatrichosoma cynomolgi.

Mode of transmission: Initial mode of transmission is unknown; however, embryonated eggs are deposited in the cutaneous stratified squamous epithelium of the nasal cavity and sloughed.

Disease characteristics: Parasite appears in the nasal epithelium of Old World primates, but they often present no clinical signs. Skin lesion can include peeling of the epidermis of the palms of hands and the bottom of the feet. Enlargement of regional lymph nodes has been documented. Pathological findings include gross evidence of serpentine tracts through the epidermis, which are signs of parasite migration and local inflammation [188,539-541].

Diagnosis: Histology, identification of parasites and eggs from nasal or epidermal swabs or skin scrapings [2].

Treatment: Fenbendazole, 10 - 25 mg/kg PO, SID, for three to ten days [2,501].

Cutaneous Mites - zoonotic

Infectious agent: Genera: Sarcoptes, Demodex, and Psorergates.

Mode of transmission: Direct contact.

Disease characteristics: Zoonotic [542]. Sarcoptes causes a variety of skin disorders than can include alopecia, erythematous macule formation, and thickening and wrinkling of the skin. Ultimately, severe infection can lead to death [543]. Demodex is a normal inhabitant (lips and brow) found on nonhuman primates and multiple animal species. Demodex does not cause clinical signs in immunocompetent animals. Psorergates causes focal non-pruritic cutaneous plaques. Clinical signs of acariasis include pruritus and dermatitis [544].

Diagnosis: Microscopic identification, deep skin scraping.

Prevention: Periodic (every 2 - 3 weeks) treatment with ivermectin 0.2 mg/kg is effective in preventing the disease and has greatly reduced the incidence of infection [501,544].

Treatment: Ivermectin (0.2 mg/kg - 0.5 mg/kg body weight, SC, once a week for two weeks). Rotenone 5% (stock solution 1:3 dilution with mineral oil, topical application, once a week for two weeks) [545]. Sarcoptes has been successfully treated with subcutaneous ivermectin (0.2 mg/kg for 5 days), supplemented with antihistamine and B-complex [543].

Lice

Infectious agent: Order: Siphunculata (Anoplurean or sucking), Mallophaga (biting lice).

Mode of transmission: Direct contact.

Disease characteristics: Mite infestation is clinically referred to as pediculosis and associated with primates in single housing units [546,547]. Lice and eggs (nits) are observed on the hair and skin.

Diagnosis: Microscopic or direct examination of organisms.

Treatment: Dichlorvos spraying in cases of severe infestation, ivermectin 0.2 mg/kg SC, repeat treatment in 2 - 3 week intervals [501,546,547].

Prevention: Isolate newly arriving animals; prophylactic treatment of animals.

Nochtia

Infectious agent: Nochtia nochti.

Mode of transmission: Oral or direct contact.

Disease characteristics: There are usually no clinical signs associated with this disease. Pathological findings of this disease include the presence of polyps. Examination of these papillomas show that they contain bright red parasites and their eggs; these lesions are located at the junction of the fundic and pyloric regions of the stomach [188,548,549].

Diagnosis: Identification of eggs in feces and necropsy examination of gastric polyps containing parasites [501].

Treatment: Unknown.

Prevention: Good sanitation.

Oesophagostomum (nodular worms)

Infectious agent: Family: Trichonematidae; Oesophagostomum stephanostomum.

Life cycle: Ingested larvae penetrate the colon wall and begin the third ecdysis. A majority of the larvae are killed in the colon wall by the host immune reaction while the rest migrate to the lumen in a few days.

Mode of transmission: Oral; direct contact.

Disease characteristics: Old World monkeys infected with this parasite are usually asymptomatic. In clinical cases involving heavy parasite load, diarrhea and anemia have been noted. Pathological findings include characteristic nodular lesions (3 - 4mm) that involve the submucosa and muscularis of the large intestine. These brown nodular lesions are caused by the larval forms on the parasite. Microscopic examination of the nodules shows the larva, abscessed core, and associated inflammation and fibrosis [550-552].

Diagnosis: Eggs and larvae in feces, fecal floatation, necropsy examination.

Treatment: Thiabendazole (22 - 100 mg/kg PO for two days), mebendazole (40 mg/kg PO, divided dose TID for three to five days), and levamisole (10 mg/kg PO or SQ, SID) [2]. All treatments should be repeated in ten to 14 days [501].

Prevention: Good sanitation.

Pentastomes

Infectious agent: Genera: Armillifer, Porocephalus.

Life Cycle: Primary host is a primate-eating snake (adult form is found in lung). Primate is the intermediate host.

Mode of transmission: Oral.

Disease characteristics: There are generally no clinical signs that are associated with this disease. Fatal peritonitis can occur during heavy infestation due to the penetration of parasites through the intestinal wall. On necropsy, nymphs (C-shaped) can be found in the pleural and peritoneal cavity [188,503,553,554].

Diagnosis: Incidental finding during necropsy examination.

Treatment: No reported treatment [501].

Prevention: Disruption of life cycle

Physaloptera

Infectious agent: Physaloptera tumefaciens, Physaloptera dilatata.

Mode of transmission: Oral, ingestion of intermediate host (cockroach).

Disease characteristics: Clinical signs are not usually noted. Adult parasites are found attached to the gastric mucosa. Pathology occurs from the attachment of parasites to the affected organ. Gastritis, esophagitis, enteritis, erosion and ulceration of the gastric mucosa has been noted [501].

Diagnosis: Identification of eggs in feces, identification of adult worms, a formalin-ether fecal sedimentation [501,555,556].

Treatment: Thiabendazole 300 mg/day for six days and levamisole 10 mg/kg/day for three days have proven effective [501,555].

Prevention: Good sanitation.

Respiratory Mites

Infectious agent: Pneumonyssus simicola, Pneumonyssoides mites are found in the lungs of nonhuman primates. Rhinophaga is found in the nasal cavity.

Mode of transmission: Close contact.

Disease characteristics: Monkeys are primarily asymptomatic. Lung mites are present in nearly all rhesus monkeys. Selected species of primates such as langurs and proboscis monkeys can have serious clinical complications [557]. Pathological findings include the presence of focal, one to ten millimeter diameter air filled sac on the pulmonary parenchyma. Fibrous adhesions develop between the visceral and parietal pleura. Bronchial lymph nodes are deeply pigmented due to the deposition of mite pigment. Histological evaluation of affected lung parenchyma shows evidence of bronchiectasis and eosinophilic granulomatous inflammation [501,558,559].

Diagnosis: Histopathology, tracheobronchial washings (not definitive), and fecal examination [501].

Treatment: Ivermectin 0.2 mg/kg, single injection [557-560].

Prevention: Periodic treatment with ivermectin is effective in preventing the disease and has greatly reduced the incidence of infection [560].

Schistosoma

Infectious agent: Schistosoma haematobium, Schistosoma mansoni, Schistosoma japonicum.

Mode of transmission: Ingestion of intermediate host (snail).

Disease characteristics: There are usually no clinical signs associated with this disease. Phlebitis and thrombosis can occur. Black pigment can be seen in the liver and spleen. Granulomas with eggs present can be commonly detected in the liver. Eggs may occur in the circulatory system, particularly the portal vein, and are identified by the characteristic location of the spine’s location on the egg [188,561-563].

Diagnosis: Identification of characteristic eggs (S. haematobium- elongated ovoid shape, posterior terminal spin; S. mansoni-elongated ovoid shape, lateral spine, S. japonicum- ovoid shape, no spine) in feces and urine, identification of adult parasites at necropsy [501].

Treatment: Praziquantel 56.8 mg/ml, use an empirical dose of 0.2 ml for nonhuman primates smaller than one kilogram and 0.1 ml/kg for nonhuman primates greater than two kilogram [501].

Strongyloidis

Infectious agent: Order: Rhabditida, Family: Strongyloididae; Strongyloides cebus (New World monkeys), Strongyloides fuelleborni (Old World monkeys).

Life Cycle: Adult females burrow into the mucosa of the proximal small intestine. Larva hatch and migrate to the lumen (L1), both L1"-"L3 larvae can pass outside host with feces, or L3 larvae can penetrate the intestine before being passed in feces (hyperinfection) causing a marked inflammatory response. L3 larvae can also pass out with feces, or remain attached to the perianal region penetrating the skin, thus leading to autoinfection. Finally, L3 larvae passed in feces of the original host can infect another host.

Mode of transmission: Oral, direct contact (skin penetration).

Disease characteristics: In healthy primates clinical signs of disease are not apparent. However, with heavy parasite infections, animals may present with diarrhea. Additionally, marked larva migration through the lungs can result in coughing or hemorrhaging in the lungs. Resultant pathology associated with parasite infestation is due to adult females burrowing into the mucosa of the proximal small intestine. Adult females lay their eggs in these mucosal burrows and once the eggs hatch, the larvae excavate out of the burrows to the lumen of the intestine (see life cycle). Therefore the natural tunneling activity of both the adult females and larvae can lead to a marked inflammatory response [564,565].

Diagnosis: Fecal floatation, presence of larvae or ova, histology, gross examination on necropsy.

Treatment: Ivermectin; 0.2 mg/kg, IM or PO [566], thiabendazole, 50 - 100 mg/kg PO for one to five days, mebendazole 22 mg/kg/day PO or SQ for two to three days, levamisole 10 mg/kg PO or SQ for two to three days, pyrantel pamoate 11 mg/kg PO SID, repeat all treatments except ivermectin in ten to fourteen days [2,501,537].

Prevention: Proper quarantine period of new animals, deworming protocols for new animals entering colony, and proper sanitation [2,501,567].

Fungal Diseases of Nonhuman Primates

Candidia

Infectious agent: Candida albicans.

Mode of transmission: Candida albicans is a normal saprophytic inhabitant of the mucous membranes and alimentary tract, genital tract, and skin of nonhuman primates [568].

Disease characteristics: Opportunistic organism which occurs in immunodeficient or debilitated animals or animals undergoing long term antibiotic therapy. Pathological findings include the presence of a white pseudomembrane on the oral and esophageal mucosa.

Diagnosis: Positive identification of organisms on hematoxylin & eosin (H&E), best demonstrated with periodic acid-schiff (PAS) or gomori methenamine silver (GMS) stains.

Treatment: Oral nystatin 200,000 U, PO QID until two days following recovery [2,157,351,569].

Cryptococcus

Infectious agent: Cryptococcus neoformans.

Mode of transmission: Inhalation; spread in pigeon (Columbia liva) droppings.

Disease characteristics: Ocular lesions and neurological aberrations have been noted. Central nervous system signs include depression, seizures, and blindness [570,571]. Gross pathology findings include the presence of gelatinous nodules on the meninges or an organized granulomatous mass. Emaciation, splenomegaly, granulomatous pneumonia, and lymphadenopathy have been noted [2,570].

Diagnosis: Fecal culture; identification of organisms in feces using light microscopy; GMS staining.

Treatment: Fluconazole or 5-Fluorocytosine. Strains may become resistant.

Prevention: Strict sanitation of housing areas [154].

Histoplasma

Infectious agent: Histoplasma capsulatum var capsulatum, Histoplasma capsulatum var duboisii.

Mode of transmission: Aerosol, inhalation of spores from H. capsulatum found in soil contaminated with bird and bat excreta. Histoplasma duboisii can be transmitted by dermal contact.

Disease characteristics: Latent infection. In immunocompromised animals, weight loss, anorexia, dyspnea, and splenomegaly have been documented [572]. Granulomatous inflammation in affected organs has been noted. Histiocytes are commonly filled with the yeast form (two to four micrometers) of the organism. Histoplasma duboisii causes African or large form histoplasmosis. Lesions are confined to the skin regions of primates (baboons) that are commonly in direct contact with the ground. Lesions consist of numerous raised or ulcerated skin lesions. Pathological findings include pyogranulomatous inflammation of the dermis and subcutaneous histiocytic infiltrates [573]. Yeast cells can be detected both intra and extracellularly eight to 15 μm throughout lesions [2].

Diagnosis: Histologic appearance of yeast using PAS or GMS stains. Immunodiffusion and complement fixation test cannot differentiate between various species of Histoplasma.

Treatment: Long term treatments with ketoconazole and trimethoprim-sulfamethoxazole PO have proven ineffective [351]. Other azoles (itraconazole, fluconazole) and amphotericin B can be used; renal function must be monitored when giving amphotericin B.

Pneumocystis

Infectious agent: Pneumocystis carinii.

Mode of transmission: Aerosol.

Disease characteristics: Clinical signs include weight loss, pyrexia, dyspnea, and anorexia. Gross pathology of lungs from primates affected by pneumocystis includes atelectasis, firm, rubber like consistency. Foamy eosinophilic intra-alveolar exudates mixed with alveolar macrophages have been noted [574].

Diagnosis: Diagnosis of P. carinii infection is confirmed by histology sections of pulmonary tissue. Cystic Pneumocystis organisms can be demonstrated with GMS or PAS staining [2].

Treatment: Trimethoprim-sulfamethoxazole, dapsone, and aerosolized pentamidine have been effective in prophylaxis and treatment protocols used in humans [2]. Additionally, atovaquone, and clindamycin have proven effective against P. carinii infection [575].

Non-infectious Diseases of Nonhuman Primates

Airsacculitis

Etiology: Opportunistic bacterial infection of the air sac.

Clinical Characteristics: Several nonhuman primate genera (Pongo, Papio, and others) have saccular diverticula of the respiratory tract, which extend into the subcutaneous tissue of the neck. Orangutans (Pongo) have air sacs that extend into the axillae. A wide variety of bacteria, particularly fecal organisms, can cause purulent inflammation of these organs, which clinically results in fluctuant swellings of the neck. Purulent bronchopneumonia can result due to aspiration of purulent exudates [576].

Treatment: Surgically open cavity and drain lesion. Administer appropriate antibiotic therapy.

Endometriosis

Etiology: Specific cause is undetermined. Associated with repeated hysterectomies, cesarean sections, advanced age, and multiparity; and can also occur without these factors.

Clinical Characteristics: Can be asymptomatic. May have palpable abdominal masses, distress associated with menstruation. Pathologic findings include the presence of multiple pelvic adhesions, cysts containing opaque brown fluid, and enlarged uterus. Lesions often contain histologically normal differentiated uterine endometrium [577-580].

Diagnosis: Clinical signs, serology, diagnostic imaging techniques, surgical examination, and pathological examination of lesions.

Treatment: Hormonal therapies (danazol, 400 - 800 mg/24 hours to the point of amenorrhea, leuprolide acetate, 0.5 mg SQ, SID for six months), progestional agents, hysterectomy with salpingo-oophorectomy, and adjunctive therapy using non-steroidal anti-inflammatory agents [579-582].

Fight Wound Trauma

Etiology: Aggressive interaction. Intraspecies aggression will vary between social housing arrangements and scenarios.

Clinical characteristics: Traumatic lacerations, full thickness puncture wounds, marked soft tissue trauma (Figure 32) [583,584]. Marked subcutaneous tissue and muscle damage has been noted. Males induce lacerations due to the prominent canine teeth. Females induce extensive crushing injuries. Fight wound trauma can occur anytime nonhuman primates are housed together. Unmanaged wounds commonly become infected with enteric bacterial pathogens along with Staphylococcus and Streptococcus species [576].

Pathology: Extensive muscle necrosis, gangrene, myoglobinuric nephrosis, and hyperkalemia are often noted during necropsy. Pathological exertional rhabdomyolysis associated with pectoral muscles is a common [585].

Treatment: Wound care and appropriate antibiotic therapy; housing adjustments if necessary.

Illustration of the damaging effects a bite wound has on superficial and deep tissue [583,584]. Illustration by AE Hawley.
Figure 32. Illustration of the damaging effects a bite wound has on superficial and deep tissue [583,584]. Illustration by AE Hawley.

Gastric Dilation

Etiology: Specific cause is undetermined. Possible factors include accidental overfeeding, normal feeding after food restriction, decreased gastric motility, and the bacterial pathogen Clostridium perfringens.

Clinical characteristics: Symptoms include abdominal distention, shock, hemorrhage from nose and mouth. Primates are often found dead. Pathological findings include marked dilation of stomach which is gas filled [486,586].

Diagnosis: Clinical signs, pathological lesions. Must rule out post-mortem gas accumulation.

Prevention: Feed primates smaller, more frequent meals (BID, TID).

Hyperthermia

Etiology: High ambient and environmental temperatures, dehydration, poor temperature conditioning, overexertion (flight, fright, or fight).

Clinical characteristics: Pyrexia, disorientation, dehydration, depressed mentation, coma, petechiation, and death. Animals should be conditioned to temperate environment. Primates should not be abruptly removed from air conditioned facilities to outside or facilities with marked increase in ambient temperatures.

Pathology: Petechial hemorrhages on the epicardium (most consistent finding), hemorrhage of serosal surfaces, and pulmonary congestion. Histologically there is extensive rhabdomyolysis.

Hypothermia

Etiology: Low environmental temperatures, insufficient supplemental heating during procedures, poor circulation.

Clinical characteristics: Decreased body temperature below normal reported limits.

Pathology: Necrosis of extremities in cases involving frostbite.

Lead Toxicosis

Etiology: Ingestion of lead based paints. Clinical characteristics: Central nervous system dysfunction (seizures, blindness, mental dullness). Pathological examination of tissues may not show lesions. Histopathology findings include cortical degeneration, acid-fast inclusion bodies noted in nuclei of renal tubular epithelium [587-592]. Diagnosis: Demonstration of exposure, toxicological analysis of tissues. Prevention: Prevent exposure, particularly from cages and enrichment devices.

Obesity

Etiology: Genetic predisposition (may be species-specific), ad libitum feeding, or high social rank.

Clinical characteristics: Deposits of adipose tissue, typically intra-abdominally. Sequelae include diabetes and cardiovascular disease.

Diagnosis: Various criteria have been used to define obesity: a monkey may be considered obese if its body weight is greater than two standard deviations above the mean for its sex, or if its body mass is composed of over 25% fat (using tritiated water or other methods) [4].

Treatment: Decrease daily caloric intake, eliminate ad libitum feeding, encourage play and other activities.

Prevention: Feed healthy animals a diet sufficient only to maintain weight, avoid unnecessary treats, balance energy input and output.

PCB And PBB Toxicosis

Etiology: Exposure to polychlorinated biphenyls (PCBs), polybrominated biphenyls (PBBs).

Clinical characteristics: Chemical amounts (< 300 ppm) result in alopecia, subcutaneous edema, leukopenia, anemia, hypoproteinemia and increased aspartate aminotransferase (AST) levels. Studies have shown that amounts (< 1ppm) in food or water caused menstrual abnormalities, reduced fertility, and small fetuses. Pathology findings include proliferative gastritis, enteritis, and occasional ulceration [593-604].

Diagnosis: Toxin screening of tissue samples, demonstration of exposure.

Prevention: Eliminate toxins in environment. Eliminate the use of PCB-containing concrete sealers in and around primate enclosures.

Self Injurious Behavior

Etiology: Psychological disorders, physiological disorders.

Clinical Characteristics: Can be expressed as hair pulling, head banging, aberrant behavior, and other forms of self mutilation [605].

Case Report: A 12 year old male rhesus monkey began self mutilating his testicles after recently being moved to another cage directly across from a new male rhesus.

Treatment: Chlorpromazine (3.0 mg/kg/day PO); range 2 - 9 mg/kg/day. Once the behavior has disappeared, the drug dosage can be decreased and perhaps even withdrawn. Haloperidol (0.2 mg/kg/day PO), fluphenazine (12.5 mg/week IM), oral L-tryptophan (TRP) supplementation (100 mg/kg twice a day).

Environmental: House self-abusive animal and submissive subordinates in the same room to decrease self-biting. Nonhuman primates should be group housed whenever possible and under appropriate conditions. Minimize strong environmental stimuli and provide environmental enrichment [35-37,43].

Prevention: See environmental enrichment section.

Vitamin Deficiencies (See Dietary Requirements)

Vitamin C Deficiency (Scurvy)

Etiology: Inadequate dietary vitamin C (ascorbic acid). Clinical characteristics: Scurvy often occurs as a result of food being improperly stored or fed beyond its three month expiration date. Symptoms include weakness, weight loss, coagulopathies, loss of teeth, anemia, and reduced immunity to disease. Pathologically, there will be hemorrhages at all tissue layers and in joints as well as decreased bone formation or fractures at epiphyses. Due to reduced immunity, many animals die before the deficiency is discovered and treated [576]. Diagnosis: Nonhuman primates commonly die of infectious disease before the development of overt clinical signs. Evaluate diet. Clinical diagnosis can be made by blood chemistry, including increased concentrations of glycoproteins, mucoproteins, creatine, and non-protein nitrogen. Treatment: Correct dietary supplementation immediately [606], and administer 50 mg of ascorbic acid IM, SID for squirrel monkeys, or two doses of 250 mg ascorbic acid IM plus oral supplementation, or 25 mg per kilogram ascorbic acid IM, BID for 5 days [606-608]. Prevention: Make sure diet has adequate vitamin C; 1 - 5 mg/kg daily needed for growth. 5 - 10 mg/kg QD up to 20 for Callitrichidae.

Vitamin D Deficiency

Etiology: Inadequate dietary vitamin D.

Clinical Characteristics: Vitamin D is another crucial dietary element for nonhuman primates, as it is essential in the absorption of calcium and phosphorus to build bone. The body is also capable of synthesizing Vitamin D through the skin. However, many nonhuman primates lack exposure to sunlight, so they need a diet that provides sufficient amount of Vitamin D in a form that their bodies can process. Rickets is a disorder that affects the growing bones of young animals. Osteomalacia is a disorder that affects mature animals characterized by lack of bone mineralization [606]. New World species require food containing vitamin D3, as they are unable to metabolize vitamin D2into Vitamin D3 as Old World species are capable of doing. A vitamin D deficiency is marked by improper bone growth, hesitance to jump, and spontaneous bone fractures. Pathologically, there is thinning of the cortical compact bone where it has demineralized, and irregular swelling of the epiphyses [576,609].

Diagnosis: Symptoms as discussed above, lesions, diet analysis.

Treatment: Rickets, hypovitaminosis D2: provide D2 in diet and ultraviolet light exposure. Rickets, hypovitaminosis D3: provide 1 IU/gram of D3 in diet and ultraviolet B radiation [2].

Prevention: Provide adequate vitamin D, 2 - 8 IU/g diet; or Old World monkeys about 200 IU/day, New World monkeys about 400 IU/day.

Table 9: Symptoms of Diseases Table

Table 9. Symptoms of Diseases Table
Viral Diseases
Adenovirus	Benign Epidemal Monkeypox	Callitrichid Hepititus	Cytomegalovirus
conjunctivitis RI diarrhea pancreatitis immunodeficient animals nec alveolitis/bronc pneumonia necrosis of panc enteritis	crusted lesions epidermal cell changes	weakness anorexia respiratory distress jaundice SC hemorrhage IM hemorrhage hepatosplenomegaly pleuropericardial effusion	usually asymptommatic generalized inflammation arteritis, enterocolitis orchitis necrosis of liver/spleen inclusion bodies
Dengue	Ebola/Marburg	Encephalomyocarditis Virus	Hepititus A
human hemorrhagic fever	maculopapular rash splenomegaly petechial hemorrhages splenomegaly lymphoid necrosis fibrin dep in spleen hepatic nec interstitial nephritis necrosis of adrenal cortex necrosis of bronch/alv epithelium	spontaneous Death myofibril necrosis w/ inflammation acute heart failure myocardial damage	increased transaminases hepatomegaly splenomegaly jaundice SC lesions IM lesions pericardial effusion usually asymptommatic
Hepatitus B	Hepatitus C	Hepatitus E	Herpes B
increased transaminases chronic periportal inflammation hepatocyte necrosis usually asymptommatic	cirrhosis heptocellular carcinoma liver damage	mild portal hepatitis	oral vesicles/ulcers conjunctivitis
Herpesvirus Papio 2	Herpesvirus Saimiri	Herpesvirus Simplex	Herpesvirus Tamarinus
oral lesion (boon) genital/cutaneous lesions	lymphadenopathy hepatomegaly splenomegaly leukemia organ necrosis	oral vesicles conjunctivitis encephalitis gential legions necrotizing meningoencephalitis organ necrosis	oral vesicles death
Lymphocryptoviruses	Measles	Molluscum Contagiosum	Monkeypox
weight loss inappetance diarrhea abdominal mass EBV seropositivity lymphoma	maculopapular rash conjunctivitis facial erythema respiratory distress diarrhea mucosal necrosis	papular lesions monkeypox papules/pustules epidermal findings visceral lesions	lesions on ulcerated areas
Papillomavirus	Epstein Barr Virus	Simian Hemorrhagic fever	Simian Varicella
papillomas-skin/oral-genital mucosa	lymphoma squamous epithelial lesions	fever anorexia depression facial edema cutaneous/SC hemorrhage epistaxis DIC thrombocytopenia petechial hemorrhage hepatic necrosis	herpetic rash depression respiratory distress vesicles-oral, skin focal organ necrosis
SV40	Yaba Pox	Yellow Fever
CNS disturbance respiratory distress squamous lesions interstitial pneumonia renal tubular necrosis encephalitis demyelination PML	SC nodules-histiocytic vesicular rash pneumonia gastroenterocolitis immunosuppressive	coagulopathies hepatic lesions hepatocellular necrosis
Retroviruses
SIV	STLV-1	Simian Type D
immunodeficiency decreased T4:T8 lymphatic lesions	depression anorexia lymphadenopathy hepatomegaly splenomegaly leukemia/lymphoma	immunosuppressive lymphadenopathy splenomegaly neutropenia lymphopenia diarrhea weight loss normal T4:T8 necrotizing gingivitis/stomatitis
Bacterial Diseases
Bordetellosis	Campylobacteriosis	Colibacillosis	Helicobacteriosis
nasal d/c dyspneaa fibrinopurulent hemorrhagic bronchopneumonia	bloody diarrhea dehydration fibrinopurulent hemorrhagic bronchopneumonia	pneumonia meningitis colitis diarrhea pyelonephritis hemorrhagic gastroenteritis serositis	cellular abnormalities of stomach superficial erosions-ulcers
Klebsiella	Leprosy	Listeriosis	Moraxella catarrhalis
pneumonia serositis airsacculitis enteritis septicemia	nodular skin thickening granulomatous lesions nerve lesions lesions on cooler surfaces-ear/nose	abortion intrauterine death neonatal sepsis meningoencephalitis purulent placental villitis intrauterine pneumonia hepatic necrosis	epistaxis-nosebleed periorbital edema mucohemorrhagic rhinitis
Nocardiosis	Pseudomonas	Pseudo TB yersioniosis	Salmonella
defects in cellular immunity dyspnea epistaxis chronic wasting abdominal distension diarrhea depression coma disseminated abscesses	vasculitis w/o thrombosis nasal d/c sneezing pneumonia abscesses granulomas	death diarrhea depression dehydration abortion stillbirth hepatic necrosis splenic necrosis mesenteric lymphadenitis ulcerative enteritis	diarrheanecrotizing enterocolitis septicemia pyogranulomas
Shigellosis	Staphylococcus	Streptococcus Pneumoniae	Tetanus
distended colon mucosal exudate changes in mesenteric lymph nodes mesenteric vascular congestion mucosal to hehorrhagic	common wound infection dermatitis cellulitis abscesses fibrinous pericarditis vegetative valvitis thrombosis /infarction glomerulonephritis	death pneumonia arthritis depression meningitis dehydration	progressive stiffness (top-down) inability to prehend food pectoral abduction stiff gait trismus opisthotonus status epilepticus extensor rigidity death
Tuberculosis
death coughing enlarged lymph nodes chronic wasting splenomegaly hepatomegaly disseminated granulomas pulmonary lesions
Protozoan Parasites
Amoeba	Balantidium	Cryptosporidiosis	Encephalitozoonosis
diarrhea intestinal ulceration mild colitis fatal meningoencephalitis	diarrhea ulcerative colitis weight loss lethargy ulcerative lesions/colitis	diarrhea weight loss anorexia intest. Villus atrophy inflam-conjunctiva, tracha inflam-bronch, bile ducts inflam-pancreatic duct, gallbladder bile duct hyperplasia periductal fibrosis	stillbirth/abortion microgranulomas (brain, kidney) inf/fetus: disseminated granulomas
Giardiasis	Hepatocystosis	Malaria	Trypanosomiasis
diarrhea malabsorption	hepatic lesions	jaundice anorexiaa listlessness fever anemia splenomegaly death thrombus	lymphadenopathy hepatosplenomeg eyelid edema heaft failure death chronic myocarditis
Metazoan Parasites
Acanthocephala	Anatrichosoma	Cutaneous mites	Lice
poor condition intussusception rectal prolapse bowel perf/sepsis mechanical blockage	palmar epidermal peeling regional lymphatic enlargement	alopeica erythematous macule skin thickening wrinkling severe infection non-pruritic cutaneous plaques dermatitis	pediculosis
Nochtia	Oesophagostomum	Pentastomes	Physaloptera
polyps (fundic/pyloric-stomach)	diarrhea anemia intestinal nodules	fatal peritonitis	gastritis esophagitis enteritis erosion/ulceration of gastric mucosa
Respiratory mites	Schistosoma	Strongyloidiasis
parynchymal air sac fibrous pleural adhesions pigmented bronchial lymph nodes bronchiectasis	phlebitis thrombosis liver discoloration/lesions	diarrhea coughing lung hemorrhage intestinal inflammation
Fungal Diseases
Candidiasis	Cryptococcosis	Histoplasmosis	Pneumocystis
white oral pseudomembrane	ocular lesions neurological aberrrations depression, seizures blindness emaciation splenomeg granulomatous pneumonia lymphadenopathy	weight loss anorexia dyspnea splenomegaly granulomatous inflammation skin lesions	weight loss pyrexia dyspnea anorexia atelectasis
Non-Infectious Diseases
Airsacculitis	Enometriosis	Fight Wound Trauma	Gastric Dilation
neck swelling bronchopneumonia	abdominal masses menstrual distress pelvic adhesions cysts enlarged uterus	lacs puncture wounds crush wounds	abdominal distention shock hemorrhage from nose/mouth death
Hyperthermia	Hypothermia	Lead Toxicosis	PCB/PBB Toxicosis
pyrexia disorientation dehydration depression coma petechiation death	lethargy recombency increased anesthetic recovery time	seizures blindness mental dullness	alopecia SC edema leukopenia anemia hypoproteinemia inc aspartate aminotransferas menstrual irregularity reduced fertility small fetuses proliferative gastritis enteritis
Vitamin Deficiencies
Vitamin C Deficiency	Vitamin D Deficiency	Vitamin D OD
weakness weight loss joint/muscle pain coagulopathies tooth loss anemia death	poor bone mineralization anorexia growth inhibition bone demineralization bone softening hesitance to jump spontaneous fractures	anorexia diarrhea inc blood urea nitrogen anemia respiratory infection

Nonhuman Primate Neoplasms

Many neoplasms that have occurred in man and other animals have been found in primates and the incidence of tumors with age increases, as might be expected. The majority of reports in literature are individual cases, while reviews of tumors involving organs or systems and large primate colonies are becoming more copious. Eventually, species reviews will become more common as well. Much has been learned by studying various tumor viruses isolated from primates and certain tumors occurring in large numbers. A recent review of spontaneously occurring, radiation-induced, and chemically-induced neoplasms in nonhuman primates has been referenced for the reader [610].

Skin and Subcutis

This is probably the most commonly affected system, as it is in man. There is undoubtedly under-reporting of the benign tumors (Table 10).

Table 10: Tumors of Skin and Subcutis, Spontaneous and Induced.
Spontaneous		Induced
A) Benign	B) Malignant	Induced
Lipoma	Squamous cell carcinoma	Basal cell carcinomas (radiation)
Papilloma (viral & nonviral)	Sweat gland adenocarcinoma	Squamous cell carcinoma (chemical)
Melanoma [22]	Fibrosarcoma (viral)	Keratoacanthoma (chemical)
Histiocytoma in baboon (Yaba monkey tumor virus) [611]	Spindle cell sarcoma	Papilloma (chemical)
Hemangiomas	Malignant fibrous histiocytoma [22,612]	Subcutaneous sarcoma (chemical)
Fibroma	Myeloliposarcoma	Liposarcoma (chemical)
Mast cell tumor [613]	Subcutaneous adenocarcinoma
Basal cell tumor [614]	Subcutaneous leiomyosarcoma[615]
Apocrine cystadenoma	Subcutaneous hemangiosarcomas in a rhesus macaque [616]
Kaposi-like tumor (SAIDS)

Musculoskeletal

Primary muscle tumors appear to be poorly documented; however, bone tumors are fairly common (Table 11).

Table 11. Tumors of the Musculoskeletal, Spontaneous and Induced
Spontaneous	Induced
Osteoma (benign)	Rhabdomyosarcoma (chemical)
Osteosarcoma [617] (Rare extraosseous tumor - malignant)	Various mesenchymal tumors (radiation)
Endochondroma [618] (malignant)	Bone tumors (radiation)
Myxosarcoma (malignant)
Myxoma (benign)
Giant cell tumor (malignant)
Leiomyosarcoma (finger, malignant)
Fibrosarcoma (malignant)
Hemangioendothelioma
Rhabdomyosarcoma (1 case-Blanchard, 1988, malignant)
Chondrosarcoma - Nasal bone of a squirrel monkey [619] (malignant)

Gastrointestinal System

Tumors of the tongue and oral cavity are commonly reported. Stomach tumors, both benign and malignant, have been reported by Beniashvili [620]. These seem to have been associated with parasites. A high incidence (15%) of colonic adenocarcinomas has been reported in cotton-top tamarins by several laboratories. The disease may be related to chronic colitis, environmental stress, and Helicobacter sp. Helicobacter infection associated with colitis in marmosets may play a role in pathogenesis of both colitis and subsequent neoplasia [621-623].

Table 12: Tumors of the Gastrointestinal System. Spontaneous and Induced
Gastrointestinal System
Spontaneous		Induced
Squamous cell carcinomas of tongue, buccal cavity, larynx, pharynx and esophagus. [624] squirrel monkey [625], infant cynomolgus monkey. [626]	Hepatocellular carcinoma: Similarities between human and chimpanzee tumors [627]; squirrel monkey [628,629]; cynomolgus monkey[630]	Hepatocellular carcinoma in a chimpanzee with schistosomiasis [631]
Salivary gland adenocarcinoma	Cecal adenocarcinoma [632], squirrel monkey	Hepatocellular carcinomas (chemical)
Mixed salivary gland tumor	Rectal carcinoma Capped Langur [633]	Hepatomas (chemical)
Mucoepidermoid cystadenoma	Intestinal leiomyosarcoma [634]	Bile duct carcinomas (chemical) aflatoxin
Salivary gland adenoma	Brunner's gland tumors
Intestinal adenocarcinoma	Gastric stromal tumors - newly recognized in NHP's & man. Of neuroectodermal and mesenchymal origin [635]
Adamantinoma	Hepatoma
Odontoameloblastoma (Japanese macaque) [636]	Cholangiocarcinoma
Gastric polyps and adenovirus	Bile duct adenoma and adenocarcinoma
Gastric adenocarcinoma- de Brazza’s guenon [636]	Hepatic hemangioendothelioma
Gallbladder carcinoma	Pancreatic adenocarcinoma
Gastric sarcoma	Pancreatic carcinoid (tree shrews)
Carcinoid tumors (duodenum)	Pancreatic ductal adenoma
Malignant rhabdoid tumor (stomach wall) [637]	Myelolipoma (liver and other miscellaneous sites) [638]
Ameloblastic odontoma (4th case in NHP [457]). Unique in that it was discovered clinically and successfully removed by surgery [639]	Colonic adenocarcinoma: common cause of death in old Rhesus monkeys of both sexes. Intestinal adenocarcinoma in geriatric macaques at the CRPRC [640],Colonic adenocarcinoma in older rhesus macaques [641]
Gall bladder adenoma in chimpanzee [642]

Cardiovascular System

Hemangiomas have been reported in subcutaneous tissue, brain, muscle, uterus, liver, kidney, bone, and spleen [616,643,644].

Respiratory System

Lung tumors are not commonly reported in nonhuman primates. A review of lung tumors is referenced [337]. There is a review of tumors in tree shrews (8/54 adults) and callitrichids (3/409 adults) from the German Primate center between 1978-1994 [645].

Table 13. Tumors of the Respiratory System, Spontaneous and Induced.
Spontaneous	Induced
Nasal fibromyxoma	Pulmonary adenomas (beryllium)
Nasal adenocarcinoma [646]	Epidermoid carcinoma (Polyaromatic hydrocarbons)
Nasopharyngeal carcinomas marmosets [647]
Nasocarcinoma (5th case of nasal cavity tumors in NHP) [648]
Laryngeal fibroma
Olfactory neuroepithelioma
Multiple pulmonary carcinoid
Bronchoalveolar carcinoma
Bronchoalveolar adenoma [649]
Multiple pulmonary adenoma
Clear cell carcinoma [337]
Pulmonary squamous cell carcinoma, Macaca fascicularis [650]
Cartilaginous hamartoma (Macaca fascicularis) [650]

Endocrine

A review of endocrine tumors in New World primates has been published [651]

Table 14. Tumors of the Endocrine System, Spontaneous and Induced.
Spontaneous	Induced
Islet cell adenomas	Thyroid adenoma (radiation)
Islet cell carcinoma [652]
Thyroid adenoma
Thyroid adenocarcinoma
Pituitary adenoma [653].
Adrenal ganglioneuroma [651]
Adrenal hypernephroma
Adrenocortical adenoma
Adrenal fibroma
Pheochromocytoma [654] - cotton-top tamarin.
Paraganglioma
Adrenocortical carcinoma
Adrenal myelolipoma [638] - marmoset [655] - tamarin.
Benign solitary parathyroid adenoma in baboon [656]

Genitourinary System

Tumors of this system are fairly common, particularly those of the female reproductive tract, probably because of the preponderance of breeding females in most primate colonies. Many renal tumors are bilateral and some appear familial.

Table 15. Tumors of the Genitourinary System.
Kidney and Urinary Bladder	Uterus, Ovary and Mammary Gland	Penis, Testes and Prostate
Renal adenoma	Ovarian teratoma [657]	Interstitial cell tumor
Renal adenocarcinoma [658]	Ovarian cystadenoma	Seminoma [659]
Nephroblastoma	Ovarian carcinoma [660]	Sertoli cell tumor
	Dysgerminoma	Prostatic carcinoma [661]
Undifferentiated bilateral renal sarcoma [662]	Mammary adenocarcinoma - Not apparently common as in women (some may be virus associated) Greater Bushbaby[663]; male squirrel monkey[664] 2-year-old female mandrill (Mandrillus sphinx), [665]	Penile papilloma - Found by genetic probes that this is tumor caused by papillomavirus - reacted most strongly with human papilloma virus type 11. Could be a good model for venereal papillomas in man [666].
Transitional cell carcinoma - urinary bladder	Spontaneous mammary gland ductal carcinoma in situ in a 6 - 8-year-old female rhesus macaque [667]	Demonstration that these oncogenic tumor viruses are venereally transmitted in rhesus monkeys [668].
Transitional cell papilloma - urinary bladder	Uterine adenocarcinoma -Case report and review of the literature [657]. Uncommon.
Transitional cell carcinoma - renal pelvis	Squamous cell carcinoma of the cervix
Review of spontaneous mammary gland tumors in rhesus monkeys [667]	Uterine leiomyosarcoma (Epithelioid subtype in a pig-tailed macaque [665,669,670] Rhesus - case report.
Review of ovarian neoplasms [660]	Hemangioma
	Uterine leiomyoma
	Brenner Tumor
	Uterine mesothelioma
	Luteoma
	Arrhenoblastoma
	Endometrial stromal tumor. Subtype arising in endometrial tissue in endometriosis away from the uterus - "endolymphatic stromal myosis" [671]
	Uterine choriocarcinoma
	Granulosa cell tumor - [657] [660]
	Mixed mammary tumor
	Spindle cell sarcoma
	Uterine sarcoma [672]
	Fibrothecoma

Nervous System

There have been few reports of neoplasia of the primate nervous system.

Table 16. Tumors of the Central Nervous System, Spontaneous and Induced.
Spontaneous	Induced
Glioblastoma [673]	Glioblastoma (radiation) [674]
Neuroectodermal tumors, both intracranial and extracranial in a black and Colobus monkey [675].	Astrocytoma - Associated with SV40 virus in an SIV inoculated macaque. Virus was associated with the tumor but no where else in the brain. Polyomaviruses are known to be oncogenic but never associated with human or primate tumors before [676]
Astrocytoma of pituitary neurohypophysial origin [677]
Lipoma of the choroid plexus-baboon [678].
Melanoma (peripheral nerve)
Medulloblastoma
Schwannoma (intestinal) [679]
Melanotic ependymoma [680]
Esthesioneuroblastoma (olfactory nerve) [620]
Meningioma in a long-tailed macaque [22]
Astrocytoma [681].

Hemopoietic System

Neoplasms of the hemopoietic system consist of spontaneously occurring, viral induced and chemically induced. Referenced in this section are recent reports of hemopoietic neoplasms of nonhuman primates [231,265,286,290,337,338,340,344,371,610-675,677-726].

Table 17. Hemopoietic System, Spontaneous and Induced.
Spontaneous	Induced
Malignant lymphoma review - Malignant lymphomas of unknown cause [714]. Subtyping of a large cell lymphoma in a chimpanzee using immunohistochemistry [701].	Erythroleukemia in infant chimpanzees receiving milk containing bovine leukemia virus
Reticulum cell sarcoma (misnomer)	Myelogenous leukemia (radiation)
Thymoma
Granulocytic leukemia
Myelomonocytic leukemia
Eosinophilic myelocytoma- Description of a case of eosinophilic leukemia with solid tumor. Mentions that eosinophilia and scattered eosinophilic infiltrates in tissues are very common in karyotype VI (32%), also karyotypes, II (11%), III (9%) and IV (5%) but not in karyotypes I [699].
Plasmacytoma (Waldenström’s macroglobulinemia--good review of plasma cell dysplasias [705]
Hodgkin (baboon)
Chronic lymphocytic leukemia [217]
T-cell leukemia [340]
T and B cell lymphomas in Cotton-top tamarins- 3 cases between 1979 and 1998 at German primate center [711]

Clinical Methodologies

Drug Administration And Injection Methods

Some drug compounds can be given orally, while others require parenteral administration to bypass the gastrointestinal system, as stomach acids can break down some molecular compounds. A number of factors influence the decision as to which route is appropriate for the administration of a compound, including: pH, volume, solubility, and effect on tissue. Additional considerations might include the animal’s disposition, housing situation, and the technician’s skill level. Refer to drug inserts for dosage and route information.

Oral Administration can include self-administration or nasogastric and orogastric gavage. Compounds can be self-administered by incorporation into an animal’s water, a treat such as fruit, jello, juice, or nearly any other compatible item that is palatable to the animal. Drawbacks to self-administration include decreased appetite due to illness and a lack of control over dosage. Additionally, the characteristics of the compound must be considered; importantly, some unpalatable flavors are extremely difficult to mask, making self-administration of these drugs difficult. Nasogastric Gavage can be performed on both conscious and sedated animals; the maintenance of a swallow reflex aids in the placement of the tube. Orogastric gavage is preferred for the smaller New World species, using five to eight French stomach tubes. The generally accepted maximum volume for administration to the stomach is 10 ml/kg bodyweight in order to avoid esophageal reflux or overflow directly into the small bowel. Orogastric gavage can also be used to administer drug capsules. Refer to Fortman et al. for procedural information [1].

Parenteral Administration routes include intravenous, intraperitoneal, intramuscular, subcutaneous, and intradermal. Intravenous administration of compounds and fluids most often occurs to nonhuman primates that are anesthetized for procedures and those that are instrumented with indwelling catheters (see Vascular Access Ports and Indwelling Venous Catheters, below). Intravenous access is possible in conscious nonhuman primates, but requires operant conditioning for the animal and an experienced technician. Intraperitoneal administration can be accomplished with the placement of osmotic pumps which release an agent over a specific period of time, or by injection of a compound into the abdominal cavity. The intraperitoneal technique requires that negative pressure be applied to the syringe before injection to ensure that the agent is not injected into the digestive tract or the bladder.

Intramuscular injection is a common technique used with nonhuman primates, which is simplified by squeeze-back cages. The preferred muscle group for IM injection is the anterior muscles of the thigh. For injection into the hamstring, the needle should be directed away from the caudal aspect of the femur in order to avoid involvement with the sciatic nerve and possible damage to it. Alternate injection sites in large animals are the triceps and gluteal muscles. The IM injection route can be painful, as muscle fibers are placed under tension by the injected fluid. Additionally, oil-based substances can require on the order of 24 hours to absorb into an animal’s system when this route is used [727]. Subcutaneous administration of fluids is a common practice when intravenous administration is not sensible. The most common injection site is between the shoulder blades, and in a sedated animal, the skin is tented before the needle is inserted and the fluid injected. Some drug compounds are also administered subcutaneously [1].

Intradermal administration involves injection of a compound within layers of the skin. This technique is most commonly used for testing purposes, and the maximum volume is typically 0.1 ml [727]. See Tuberculosis test administration and interpretation, below, and Fortman et al. for more information on intradermal injection techniques [1].

Tuberculosis Test Administration and Interpretation

Diagnosis of tuberculosis can be made based on the intradermal tuberculin test using mammalian old tuberculin (Intradermic, Colorado Serum Co., Denver, CO; marketed by Synbiotics Corp., Animal Health Division, San Diego, CA) [443]. The intradermal tuberculin test in the upper eyelid with at least 1500 Tuberculin Units (TU) of tuberculin is uniformly accepted, using 1500 TU = 0.1 cc of a 1:10 dilution of mammalian tuberculin (Figure 33) [76,728]. This product contains 150,000 TU/cc. Also acceptable is a higher concentration, using a 1:6 dilution with distilled water and 0.1 ml/site is used. Therefore, 2500 TU (25 mg) is injected per site [443]. The test site is observed 24, 48 and 72 hours after administration. Two examples of schemes used to interpret and categorize palpebral tuberculin are provided in Table 18 and Table 19. A second method of screening for tuberculosis is the abdominal intradermal tuberculin test. This test is sometimes used to help confirm palpebral test results or may be used as the sole screening method. Variations on abdominal intradermal tuberculin testing protocol exist. Confirmatory abdominal testing consists of shaving an area on the abdomen and demarcating two test sites with permanent marker. One test site is injected with tuberculin of a concentration and volume as described above. The second site is injected with a protein control (usually bovine serum albumin, BSA, in appropriate diluent) of an equal volume as the first test site. Results are based on the degree of swelling and erythema of the tuberculin-injected site relative to the control. The protein control serves to rule out a nonspecific reaction to a foreign protein.

Intradermal tuberculin test in upper eyelid of a baboon [11].
Figure 33. Intradermal tuberculin test in upper eyelid of a baboon [11].

Table 18. Tuberculosis Diagnosis Guide [443].
Grade	Presentation	Interpretation
I	Bruising at injection site	Negative
II	Erythema without swelling	Negative
III	Slight swelling with or without erythema	Suspect
IV	Obvious swelling with drooping and erythema	Positive
V	Swelling and necrosis	Positive

Table 19. Tuberculosis Diagnosis Guide.
Interpretation	Presentation
Negative	No swelling, erythema or lid drooping
Trauma	Bruise, erythema fans out through lymphatics, no swelling
Suspicious	Minimal swelling with or without erythema
Positive	Swelling and variable erythema, drooping of lid due to swelling, necrosis

Radiographs are generally of little value until late in the clinical course in cases that may be anergic. It has been reported that the lag time between a positive TB skin test and a radiographic diagnosis is as long as 6 months. Test Complications: false positive test results can occur in nonhuman primates exposed to Freund’s complete adjuvant [468], trauma due to improper administration of test agent, excess concentration of antigen in skin test, or nonspecific reaction to test vehicle. False negative tuberculin test results can be associated with concurrent infection with measles due to immunosuppression, prior treatment with isoniazid, latent period of infection (early), anergy (absence of a subject’s ability to generate a sensitivity reaction to substances expected to be antigenic in that individual), immunizations, steroid administration, atypical mycobacterial infections, or severe illness.

Preparing the Nonhuman Primate for Surgery

Endotracheal Intubation

Nonhuman primates are routinely intubated in order to maintain a patent airway, administer gas anesthesia, and to ensure the ability to provide emergency ventilation should a crisis occur during a procedure. Personal protective equipment is essential during intubation, particularly a mask and eye protection, as the gag reflex can be quite violent in some animals. A mouth gag should be used for infectious animals, macaques, and animals with large canines to prevent them from biting the endotracheal tube or the handler during the intubation procedure. The animal can be positioned according to personal preference. The authors place adolescent P. anubis and adult M. mulattain dorsal recumbency for intubation. A cuffed endotracheal tube (uncuffed tubes may be necessary for smaller animals), from two to eight millimeters inner diameter, should be inflated and checked for leaks prior to use, and deflated. The tube can be lubricated with water or a sterile lubricant. Using gauze, the animal’s tongue is grasped and pulled outward, and a laryngoscope with a straight or curved blade of appropriate length is inserted and placed at the base of the epiglottis. The endotracheal tube can then be advanced down the length of the blade and between the arytenoid cartilages into the trachea. Passage of the tube can be facilitated with a stylet, which should be removed immediately upon placement of the tube. Fill the tube’s cuff with enough air to prevent the escape of expired air. Auscultate each side of the animal’s chest to ensure that the endotracheal tube is in the trachea and not mainstem bronchi. If only one lung is inflating, withdraw the tube slightly and re-auscultate. Secure the tube with gauze by tying first around the tube, and then around the animal’s head. The animal is ready to be extubated when it has recovered its gag reflex; the cuff should be deflated prior to removing the endotracheal tube [1,155].

Intravenous Catheter Placement

Placing an intravenous catheter soon after inducing anesthesia in a nonhuman primate is a wise safety measure, as direct venous access can be crucial in the event of an anesthetic emergency. These are also useful for the infusion of supplemental fluids and the administration of many other drugs. For larger animals, an 18 gauge Teflon catheter with a metal stylet is appropriate for the saphenous vein, and smaller catheters (of higher gauge) are suitable for smaller species or the cephalic vein of the arm in larger species.

Restraint Methods for Nonhuman Primates [1]

There are three types of restraint for nonhuman primates: chemical, physical, and operant conditioning. Chemical restraint is generally in the form of the injectable drugs (see Anesthesia, Analgesia, and Euthanasia). Remote injection systems are available to aid in the capture of free-ranging animals and those in large pens. The use of chemical restraint requires that the animal receive physiological monitoring until normal activity is resumed.

Physical restraint can involve the use of squeeze back cages to reduce the animal’s movement for injections, transfer chutes for cage changes and cleaning, nets for the capture of escapees, and pole and collar systems for cage changes and movement to other restraint devices. Additionally, some forms of restraint are necessary for use in research protocols that require serial blood draws, drug administration, or physiological monitoring. These methods can include restraint chairs, boxes, and tubes. Restraint boxes and tubes restrict an animal’s movement more severely than restraint chairs, and thus should be used for limited periods of time. Restraint chairs are considered to be more comfortable for the animal and can be modified for the animal and for the experimental requirements. An acclimation period, with positive (food) reinforcement, is recommended before any of these devices are used in an experimental setting. Nonhuman primates requiring chronic monitoring, infusion, or sampling can also be attached to a tether system, which allows for less restricted movement. The animals wear a jacket or backpack which protects the catheters as they exit the animal, and the catheters are housed in a flexible metal tube that attaches at a swivel to the cage. An acclimation period of at least one week is recommended when introducing animals to the tether system prior to surgical instrumentation. The Animal Welfare Act regulates the use of the above restraint devices. Manual restraint is sometimes used for short periods of manipulation on New World primates, and occasionally for smaller Old World animals. Appropriate personal protective equipment is essential during manual restraint, and varies according to animal species, size, disease status, and presence of canine teeth. All of the standard PPE should be worn, along with leather gloves and possibly metal mesh liners to provide some protection from bites, and Tyvek® or Kevlar® sleeve shields to protect from scratches. Because there is direct physical contact between the technician and the animal, there is higher risk of injury to the handler due to bites, scratches, and fluid exposure. The safest method of manually restraining a nonhuman primate involves grasping the animal’s arms above the elbows and slightly behind its back, with its back facing the handler. This also is a relatively safe position for the animal to be in for returning it to a cage, as nonhuman primates tend to retreat to the back of the cage before turning around, giving the handler a moment to close the cage door.

Medical Techniques

Amniotic Fluid Collection

Amniocentesis has been used to collect amniotic fluid samples in Old World monkeys [729-731]. There are two accepted techniques for the successful collection of amniotic fluid in nonhuman primates, an ultrasound assisted technique, and a "blind stick" technique. Both techniques are referenced in detail by Fortman et al. in "The Laboratory Nonhuman Primate" [1].

Blood Collection

Blood collection in nonhuman primates of all sizes and species is necessary for the proper periodic clinical evaluation and for medical assessment of the animals. Guidelines for nonhuman primate venipuncture have been published that can be used to calculate the safe maximum blood collection sample from nonhuman primates. A common blood draw recommendation is the 10%-10% rule. This rule states that the maximum single blood sample size without adverse effects on an animal is 10% of a blood volume estimated to be 10% of the primate’s body weight [1]. The most common site for venipuncture in nonhuman primates is the femoral vein. In larger primate species (macaques and baboons), the femoral artery can be palpated and a 21 - 23 gauge butterfly needle inserted just medial and perpendicular to the artery in order to ensure a clean venous draw (Figure 34 and Figure 35). A ten milliliter syringe is attached to the butterfly and the blood is drawn at a steady rate. The syringe is then detached from the butterfly and the blood is transferred into the necessary vacutainers using an 18 gauge needle. A more common technique is to attach a 20 - 23 gauge needle to a ten milliliter syringe and directly access the femoral vein. Larger needles can be used for larger nonhuman primates (chimpanzees: 18 - 20 gauge needle), while smaller nonhuman primates require smaller gauge needles for venipuncture (squirrel monkeys: 21 - 23 gauge needles). Other recommended sites for blood sampling in larger nonhuman primates are the cephalic and saphenous veins. In smaller nonhuman primates, such as marmosets, the saphenous and lateral tail veins are available for venipuncture. Techniques for blood collection in nonhuman primates have been referenced in detail [1,2,537,727,732-736].

Blood collection from femoral vein using a 23 gauge butterfly catheter. Photomicrograph by SK Wrobelski.
Figure 34. Blood collection from femoral vein using a 23 gauge butterfly catheter. Photomicrograph by SK Wrobelski.

Blood collection from femoral vein using a 23 gauge butterfly catheter. Photomicrograph by SK Wrobelski.
Figure 35. Blood collection from femoral vein using a 23 gauge butterfly catheter. Photomicrograph by SK Wrobelski.

Vascular Access Ports

Vascular access ports (VAP) are designed to facilitate chronic blood collection and administration of compounds. The ports are contained subcutaneously and require aseptic technique each time that they are accessed for a draw or infusion. Forman et al. outline a complete description of VAPs along with guidelines for placement in nonhuman primates [1,737]

Indwelling Intravenous Catheter with Tether

Indwelling IV catheters with tethers are commonly used in research on nonhuman primates in studies that require chronic continuous drug dosing. They require daily flushing with heparinized saline (30 IU/ml) in order to most effectively maintain patency, which frequently lasts a year and has been known to last over three years [738]. In the rhesus macaque, the following veins can be used and are listed in order of desirability: internal jugulars, external jugulars, femorals, and brachials. As the brachials are small, they tend to remain patent for only about six months. Placement of these catheters requires an aseptic procedure. Consult an experienced veterinarian or surgeon before attempting this procedure.

Bone Marrow Collection

Bone marrow biopsy using specially designed needles/trochars are used to obtain blood progenitor cell from nonhuman primates. A sterile biopsy needle is inserted into a marrow-containing cancellous section of the long or flat bones. There are several types of biopsy needles on the market that can accommodate specimen collection from both larger Old World monkeys and smaller New World monkeys. The most common blood collection sites in nonhuman primates include the dorsal anterior aspect of the iliac crest, the ischial tuberosity, the trochanteric fossa of the femur, the tibial crest, and the proximal humerus. An excellent overview of bone marrow biopsy techniques can be found in the textbook entitled "The Laboratory Nonhuman Primate" [1,739-742].

Bimanual Rectal Palpation

This technique can be used to detect reproductive disease or pregnancy in nonhuman primates, although ultrasound is now the preferred method. The primate is sedated and placed in lateral or ventral recumbency. While wearing the appropriate protective equipment, the examiner inserts a lubricated middle finger (or little finger, in the case of a small species of monkey) into the animal’s rectum and presses ventrally (toward the abdomen). Using the other hand, the examiner provides pressure on the caudal abdomen, providing a surface against which the uterus can be palpated against with the middle finger. A non-pregnant uterus is turgid, and a pregnant uterus is fluctuant or soft [1].

Cerebrospinal Fluid Collection

Cerebrospinal fluid (CSF) can be collected in nonhuman primates from either the cisterna magna or the lumbar region. Nonhuman primates undergoing CSF collection must be fully anesthetized to facilitate safe sample collection [743]. Procedures for successful CSF collection from the cisterna magna and lumbar region have been described in brief. Cisterna magna: collection should be done at the junction of a line drawn that bisects the cranial wings of the atlas and a line from the external occipital protuberance. The size of the needle gauge used for this procedure will vary among primate species. Lumbar: sample collection between the intervertebral spaces is facilitated by placing a fully anesthetized animal in a position that flexes the spine (such as the fetal position). A horizontal line between both iliac crest will bisect the intervertebral space, which is the site of needle entry. Techniques on nonhuman primate CSF sample collection have been referenced in detail [1,2,732,733,740,744,745].

Disarming Canine Teeth

Several techniques are used to disarm the canine teeth of nonhuman primates. Disarming nonhuman primate teeth is presently the subject of debate due to the high incidence of abscessation of the affected tooth. This procedure is conducted to decrease the risk and severity of bite wound trauma to personnel, other nonhuman primates, and to the primates themselves [2]. The most common techniques used to disarm teeth include complete extraction of canines [746], crown reduction followed by a mucoperiosteal flap [747], crown reduction followed by a root canal [748], or crown reduction followed by a pulpal capping procedure [1,749,750]. The crown reduction and pulpal capping technique is discussed and referenced in detail by Fortman et al. [1] This procedure is currently recognized as the least invasive technique and is associated with minimal post-operative complications.

Dental Prophylaxis

Excessive tartar and periodontal disease in non-human primates is commonly seen. Primates in captivity should have their teeth cleaned and polished to help maintain a healthy mouth (Figure 36). The examination of the oral cavity should be conducted to prevent or treat dental disease [1].

Dental exam of common squirrel monkey. Photomicrograph by R Duran-Struuck.
Figure 36. Dental exam of common squirrel monkey. Photomicrograph by R Duran-Struuck.

Nasogastric Gavage

Refer to Clinical Methodologies.

Semen Collection

Semen can be successfully collected from various species of nonhuman primates. There are several techniques that have been documented; however variation in sample size, semen morphology, motility, and viability can occur between collection techniques. Common techniques used for semen collection include rectal probe electro-ejaculation, direct penile electrostimulation, and vibratory stimulation methods. Detailed descriptions of these collection methods have been referenced in detail [1,751-754].

Urine Collection

Free catch, urethral catheterization, and cystocentesis are the major methods used for obtaining a urine sample for urinalysis. The free catch method consists of the collection of normally voided urine in a clean waste pan or metabolic cage. This method is totally noninvasive, however the urine sample is not sterile [733]. Urethral catheterization can be used to obtain sterile urine samples from a wide rage of nonhuman primates using proper sterile technique [755]. Chemical restraint along with technical expertise is required for this method. Cystocentesis is the preferred method of obtaining a sterile urine sample for a nonhuman primate and also requires technical expertise due to the anatomical location of the urinary bladder within the pelvic canal [756].

Radiography

Radiographs of the chest have proven to be a useful diagnostic tool in primate medicine. Due to the anatomical similarities of nonhuman primates and humans, human and pediatric radiograph technique charts have proven useful when evaluating nonhuman primates (Figure 37) [2].

Radiograph of femoral-tibial joint. Note the large "joint mouse" (Synoviochondrometaplasia) in the joint space. Photomicrograph by R Duran-Struuck.
Figure 37. Radiograph of femoral-tibial joint. Note the large "joint mouse" (Synoviochondrometaplasia) in the joint space. Photomicrograph by R Duran-Struuck.

Ultrasonography

Nonhuman primates under sedation or general anesthesia can be clinically evaluated using ultrasound technology. Internal anatomical structures can be evaluated in detail. Ultrasound directed biopsies, imaging of reproductive organs, and real-time imaging of the cardiovascular system can be performed using this technology [2,757]. The success of any ultrasound imaging is dependent on the type and sensitivity of the ultrasound probe used and the capabilities of the machine and its operator. Many ultrasound imagers can record and print images in several different formats [758-762].

Clinical Therapeutics

Thermoregulation

Some primates are at a particularly high risk of hypothermia. Very small animals (those under five kilograms), nonhuman primates treated with Telazol®, and those subject to procedures of long duration are in the most danger of a rapid loss in body temperature. During procedures, these animals should have their core temperatures monitored carefully, and a circulating water blanket covered by a drape can be used as a heat source on an operating table. Warmed IV fluids may also be useful. Hypothermia can slow recovery from anesthesia and can result in arrhythmias. When a caged animal is at risk of hypothermia, a carefully monitored heat lamp can be used, but caution must be taken that the metal of the cage is not hot to the touch and the animal is unable to reach the lamp. Burns are a distinct possibility with heat lamps, and the ability of the animal to move into shade is important [22].

Fluid Support for Nonhuman Primates

Any invasive procedure lasting over 30 minutes should include the administration of fluids intravenously at a rate of 10 ml/kg/hr. Lactated ringer’s solution is preferred, and can be used with or without dextrose. Blood loss should be replaced at a three-fold rate, and great care should be taken with small patients that fluid volumes are accurate to avoid volume overload [22].

Major Surgical Procedures

As established by the Animal Welfare Act, a nonhuman primate should not have more than one major survival surgery entering the abdominal or thoracic cavity unless its scientific justification is approved by the Institutional Animal Care and Use Committee (IACUC). Should the need to correct experimental complications arise, requiring another major procedure, prior approval must be established before performing further surgery. Otherwise, euthanasia may be the appropriate measure. Permission for ongoing major survival procedures must go beyond an IACUC to a request for approval from the Animal & Plant Health Inspection Service (APHIS) [763].

Principles of Wound Management. Nonhuman primate wounds caused by negative interaction between individuals are some of the most challenging for the veterinary clinician to manage. Prior to any treatment, the physical and clinical status of the nonhuman primate should be evaluated. Always evaluate respiratory system, cardiac function, and shock status of the patient first ("Save the animal, then save the wound") [764,765].

All wounds incurred by nonhuman primates should be evaluated thoroughly prior to treatment. Culture swabs can be used to acquire samples for bacterial culture and antibiotic sensitivity testing. Clinicians can also use a Gram stain or impression stain of the wound to detect the type of bacterial population(s) that is present in the wound. Systemic antibiotics should be started preferably within the first three hours of the wounding incident. Antibiotic therapy should continue for seven to ten days (see nonhuman primate formulary for antibiotics and dosages). Clinicians should consider changing or adding a second antibiotic if any of the following conditions occur: 1) culture and sensitivity test indicate the use of a different antibiotic, 2) nonhuman primate develops signs of clinical septicemia, or 3) wound appearance does not change within two to three days after initial antibiotic therapy and strict wound care.

Table 20. Principles of Wound Protection, Preparation, and Surgical Debridement [583,584].
Wound Protection/Preparation	Anesthesia/Analgesia	Surgical Debridement
Moisten gauze sponge, water soluble lubricant	General anesthesia only if patient is in stable condition	Surgical	Layer	Enbloc	Staged
Remove all debris from wound site	Local/regional anesthesia with neuroleptanalgesia	Remove devitalized and contaminated tissue	Wear gloves and mask	Completely excise the wound without entering cavity	Remove obviously dead or mangled tissue
Clip hair or fur from around the wound using a #40 clipper blade or scissors	a) Lavage or pack wound with 2% lidocaine without epinephrine on a gauze sponge before cleaning wound	Remove all foreign debris	Use sterile instruments	Must be sufficient tissue to allow procedure	Leave questionable tissue:
Clean wound edges with chlorhexidine or povidone iodinesolutions	b) Neuroleptanalgesia	Adequate hemostasis	Start at surface of wound and gradually progress to the depths of the wound using forceps, scalpel and scissors.	Extravasated chemo-therapeutic drug	Purple or hyperemic tissue may be viable; black or white tissue is usually nonviable
	c) Inject 2% lidocainew/out epinephrine through intact skin at wound margins. An injectable combination of .1 ml sodium bicarbonate for each ml of lidocaine for patient comfort.	Aggressive wound lavage	Tissue Management		Tissue separating from viable tissue is usually nonviable
	d) A 2% lidocaine ring block proximal to the wound can also be utilized	Elimination and drainage of dead space
	e) Bupivacaine

Table 21. Principles of Wound lavage and Enzymatic Debridement [583,584].
Wound Lavage			Enzymatic Debridement	Hydrophilic Agents
Principles	Techniques	Solutions	Enzymatic Debridement	Hydrophilic Agents
Floats away debris and devitalized tissue	35 ml syringe, 3-way stopcock, 18-gauge needle, intravenous administration set, container of lavage solution.	Isotonic solution	Indications- poor anesthetic risk or surgical debridement results in massive tissue damage	Draws body's homestatic fluids through wound tissues to bathe the tissue from the inside-out
Removes and dilutes bacteria		ChlorhexidineSolution 0.05%	Granulex ® spray	Hydrogel
	High pressure water spray can cause tissue damage.	Providone Iodine 1%	Elase ointment- Chloroamphenicol Fibronolysin DNASE	Mutlidex ® D-Glucose Polysaccharide- inhibits bacteria growth, chemotatic for cells involved in wound healing, stimulates granulation tissue formation, epithelialization and contraction
	Spray bottle	Hydrogen peroxide	Kymar ointment ®- Trypsin and chymotryopsin, neomycin, hydrocortisone	Sugar and betadine solution paste
		Dakins solution (sodium hypochlorite0.25%)	Trypsin-balsam of Peru-castor Oil
		Micro-Klenz ® antimicrobial wound cleanser

Table 22: Principles of Open Wound Management [583,584,766,767].
Principles of Bandaging (Figure 38)	Early Bandages (Adherent)	Late Bandages (Nonadherent)	Topical Antibiotics and Antibacterials	Topical Medications
Contact Bandage Layer: direct contact with the wound and serves to absorb fluids that drain from the wound.	Dry-to-dry: loose necrotic tissue, foreign material	Nonocclusive, semiocclusive, occlusive.	Bacitracin-Neomycin-Polymyxin(Neosporin®), poor absorption from tissue, use only on acute wounds	CarraVet® wound gel: contains Acemannan which stimulates macrophages to produce IL-1 and TNF which facilitates wound contraction and epithelialization
Intermediate Bandage Layer: covers the contact bandage and also absorbs fluids but also protects wounds from trauma	Wet-to-dry: viscous exudate	Felt-to-gel: Calcium alginate material made from seaweed. This product interacts with wound fluid exchanging calcium for sodium.	Silver sulfadiazine(Silvadene®)	Dermaide Aloe®: contains salicylates that prevent vasospasm in tissues therefore maintaining circulation and oxygen supply to tissue.
Outer Bandage Layer: a porous adhesive tape layer that holds the contact and intermediate bandage layers in place.			Chlorhexidine acetate(Nolvasan® ointment): good antimicrobial, inhibits granulation tissue	Dermaclens®-triple acid ointment: contains malic, salicylic and benzoic acid. The nonviable tissue absorbs the acid first, absorbs more fluid, then separates from the wound [583,584]
			Gentamicin sulfate
			Nitrofurazone (Furacin®)

Illustration of the three primary layers of a wound bandage: I) Contact Bandage Layer, II) Intermediate bandage layer, and III) Outer bandage layer. Illustration by AE Hawley.
Figure 38. Illustration of the three primary layers of a wound bandage: I) Contact Bandage Layer, II) Intermediate bandage layer, and III) Outer bandage layer. Illustration by AE Hawley.

Case Report

A recently weaned, one year old, 2.05 kg female rhesus monkey was reported to the veterinary staff for a swollen right arm and anorexia. On physical examination this monkey had a body temperature of 105°F and marked swelling and inflammation of the right shoulder, arm, and hand. Mucopurulent exudate in the subcutis of the forearm drained from a fistulous tract that exited between the second and third phalanges. The exudate was cultured, the fistulous tract was lavaged with 0.9% saline solution, and the forearm and hand were bandaged. The monkey was also treated with procaine penicillin G, 40,000 IU/kg intramuscularly once a day pending culture and sensitivity results. Within 24 hours a 6.5 cm x 3.4 cm area of skin sloughed. The resultant open wound was managed with wet-to-dry bandages for two days to aid in necrotic tissue debridement and exudate removal. On the third day, a non-adherent porous woven acetate dressing containing bisabolol and glycerine ointment was added as the primary bandage layer. The non-adherent dressing was easier to change daily, and it provided a moist sterile environment that enhanced the growth of healthy granulation tissue. Culture and sensitivity results yielded a coagulase positive Staphylococcus sp. that was sensitive to cefazolin sodium. Antibiotic therapy was changed to cefazolin sodium, 100 mg/kg, IM, q12 hours, for 10 days. By the seventh day after initial observation a granulation bed had formed. At this time the proximal and distal wound edges were apposed with 2 - 3 simple interrupted sutures; this closure was continued every other day 2 - 3 sutures at a time. Management of the open wound in this manner allowed it to be closed completely in 13 days, and the wound then healed uneventfully.

Case Report

A 7-year-old female, rhesus macaque was placed in a quarantine facility upon arrival at a research institution. On the day of release, she was observed pawing at and chewing on her left cheek. Physical examination (PE) revealed ulcerative lesions on the buccal surface of the left cheek. No other abnormalities were noted. Swabs of the lesions were taken for viral and bacterial isolation, and blood was drawn for complete blood count (CBC) and serum chemistry profile. Treatment with 25mg/kg cefazolin BID was initiated. Twelve days later, the animal presented with a 2x2cm, full-thickness erosion involving the opposite (right) cheek. A wedge biopsy was performed and treatment with buprenorphine (0.05mg/kg SID) was initiated. The defect was sutured, but the animal removed them. CBC and serum chemistry profile were normal. Biopsy revealed no definitive etiology. Upon further observation of the animal, it was determined that the lesions likely resulted from self-injurious behavior (SIB) manifesting as chewing on the cheeks. Treatment with the antipsychotic agent chlorpromazine (1mg/kg intramuscularly SID for 25 days, then 0.5mg/kg SID for 25 days) was initiated. She was also moved into a different room, and a "chew toy necklace" was created to serve as an alternative to further cheek biting. Medical therapy and environmental manipulation eliminated the SIB in this animal and the lesion began healing by second intention and was completely healed within 35 days.

Laboratory Animal Use in Research

The purpose of studying an animal model is to gain information which can be transferred, in part or in whole, to the human condition of interest. The animal model generally represents a simplification of the human condition, in that it is more easily defined and manipulated [767,768].

There are four basic types of animal models of disease:

Spontaneous models

These are diseases which occur naturally in animals and which mimic, at least in part, the "same" disease syndromes in humans. In most cases, the disorder in the animal model is comparable to only one or a few aspects of the human disorder.

Experimental models

These are conditions which are experimentally induced in animals and which resemble aspects of human disorders. This type of model is used most often to study diseases with identifiable and easily manipulated etiologic mechanisms, e.g., nutritional or endocrine disorders.

Negative models

These are animals in which particular pathological conditions of humans do not occur and cannot be produced. They are valuable in helping to elucidate mechanisms of resistance.

Orphan models

These are primarily pathological conditions in animals for which no comparable human disorders have been identified. Also included in this category are disorders in animals which resemble known human disorders but which have very different pathogenic mechanisms.

Advantages of Nonhuman Primates as Models of Human Disease

Nonhuman primates share a close phylogenetic proximity to humans; offer close (in many respects closer than any other species) homology to humans in terms of reproduction, embryologic development, anatomy, and physiology. They are susceptible to many human diseases and are highly intelligent and trainable.

Disadvantages of Nonhuman Primates as Models of Human Disease

The purchase price of nonhuman primates is sometimes prohibitive and they can be difficult to obtain; many institutions do not have the facilities to handle some or all species of nonhuman primates. A number of species are difficult to work with and cannot be handled safely by untrained, inexperienced personnel. Nonhuman primates are potential (often probable) carriers of a wide variety of zoonotic diseases (See Occupational Health and Safety Section). Additionally, the use of nonhuman primates in research is likely to attract the interest of animal welfare and animal rights groups.

Primate Resources

Washington National Primate Research Center - http://www.wanprc.org/WaNPRC/
Yerkes National Primate Research Center - http://www.emory.edu/WHSC/YERKES/
Southwest National Primate Research Center - http://www.snprc.org/
California National Primate Research Center - http://www.crprc.ucdavis.edu
New England Primate Research Center - http://www.hms.harvard.edu/nerprc
Oregon National Primate Research Center - http://onprc.ohsu.edu
Tulane Primate Center - http://www.tpc.tulane.edu
Wisconsin Regional Primate Research Center - http://www.primate.wisc.edu
USDA - http://www.usda.gov
CDC - http://www.cdc.gov
NIH - http://www.nih.gov
Association of Primate Veterinarians - htpp://www.primatevets.org
Primate Supply Information Clearinghouse - http://wanprc.org/psic/
Chimp Haven - http://www.chimphaven.org/
The National Sanctuary for Retired Research Primates (NSRRP) - http://www.primatesanctuarynsrrp.org
National B Virus Resource Center - http://www.gsu.edu/~wwwvir/index.html
Atlas of the Primate Brain - http://braininfo.rprc.washington.edu/menumain.html

Appendix 1

Nonhuman Primate Drug Formulary [1,56,155,769,770]

Antiparasitics
Albendazole	25 mg/kg PO Q12h x 5d (1) (2) (4)	Filaroides sp.
Chloroquine	10 mg/kg PO, IM once, then 5 mg/kg 6hrs later, then 5 mg/kg Q 24h x 2 days (1) (4)	Plasmodium sp.; treat concurrently with primaquine(0.3mg/kg/day (4))
Clindamycin	12.5 - 25.0 mg/kg Q 12(1)	Toxoplasma sp.
Dichlorvos	10 - 15 mg/kg PO Q24 x 2 - 3d(1)(2) (4) 30mg/kg PO Once (2)	GI nematodes
Diethylcarbamazine	6 - 20 mg/kg PO Q24 x 6 - 15 d(1) (4)	Dipetalonema sp.
Diethylcarbamazine	20 - 40 mg/kg PO Q24 x 7 - 21d (1) (4) 50 mg/kg SID x 10 days (2)	In orange juice
Doxycycline	5 mg/kg PO Q12 x 1d, then 2.5 mg/kg Q24 (1) (2) (4)	Balantidium sp.
Fenbendazole	50 mg/kg PO Q24 x 14 days(1) (4)	Filaroides sp.
Fenbendazole	50 mg/kg PO SID x 3 days (2) (4)	Lemur and Varecia sp., require only 3 days treatment
Furazolidone	5 mg/kg PO Q6 x 7 d (1)	Juveniles
Furazolidone	100 mg/animal PO Q6 x 7 d. (1)	Adults Great apes/Giardia sp. - less effective than other agents but more palatable
Ivermectin	200 μg (0.2 mg)/kg PO, SC, IM (1) (2) (4)	Can be repeated in 10 days.
Levamisole	5 mg/kg PO; repeat in 3weeks, 10 mg/kg PO(1) (4) 7.5 mg/kg SQ. Repeat in 2 weeks (2)	Strongyloides sp., Filaroides sp., Trichuris sp.
Mebendazole	3 - 5 mg/kg PO (2) (4) 15 mg/kg PO Q24h x 3d(1) (2) (4) 22 mg/kg PO Q24h x 3d, repeat in 3 weeks (1) (4)	Strongyloides, Necator sp., Pterygodermatitis, Trichuris sp.
Mebendazole	40 mg/kg PO x 7 days	Strongyloides sp.
Metronidazole	17.5 - 25.0 mg/kg PO Q12h x 10d (1)	Enteric flagellates and amoebas
Metronidazole	30 - 50 mg/kg PO Q12h x 5 - 10d (1) 35 - 50 mg/kg PO divided BID x 10 days (4)	Balantidium coli
Paromycin	12.5 - 15.0 mg/kg PO Q12h x 5 - 10d (1)	Amoeba; use with other agents with invasive disease
	10 mg/kg PO Q8h x 5 - 10d (1) 50 mg/kg PO in three divided doses SID for 10 days (2) (4)	Great apes/Entamoeba sp.
	10 - 20 mg/kg PO Q12h x 5 - 10d. (1)	Balantidium coli
Piperazine	65 mg/kg PO Q24 x 10d. (1) (2) (4) 100 mg/kg PO (2)
Praziquantel	40 mg/kg PO, IM once(1) (2) (4) 15 - 20 mg/kg PO, IM (1) 0.1 mL/kg IM (Droncit injectable)	Trematodes Some cestodes
Primaquine	0.3 mg/kg PO Q24h x 14d. (1) (4)	Plasmodium sp.; treat concurrently with chloroquine
Pyrantel pamoate	11 mg/kg PO, once (1) (4)	Necator sp., pinworms
Pyrantel pamoate	6 mg/kg (1) (2)	Lemurs
Quinacrine	2 mg/kg PO Q8h x 7 days (1) 10 mg/kg PO TID every 10 days (2) (4)	Great apes/Giardia sp.; max dose of 300mg/day
Sulfadiazine	25 - 50 mg/kg PO Q 6h(1)	Toxoplasma sp.; treat concurrently with pyrimethamine
Sulfadiazine	100 mg/kg/day PO (1)	Great apes max dose of 6g/animal/treatment
Sulfadimethoxine	50 mg/kg/day PO x 1 day, then 25 mg/kg/day (1) (4)	Coccidiosis
Tetracycline	15 mg/kg PO Q 8h x 10 - 14d (1)	Balantidium coli Infants, juveniles/Great apes
Tetracycline	500 - 1000 mg/animal PO Q8h x 10 - 14 days (1)	Adults/Great apes
Thiabendazole	50 mg/kg PO Q 24h x 2 days (1) (4) 75 - 100 mg/kg PO, repeat in 3wks (1) (4) 25 - 35 mg/kg PO x 4 days (4)	Strongyloides sp., Necator sp.
Trimethoprim/sulfa	30 mg/kg PO Q 6h x 14 d (1) Trimethoprim at 20 mg/kg & sulfa at 100 mg/kg/day in 4 doses PO, IM (4)	Great apes/Pneumocystis carinii
Antiviral, Antibacterial and Antifungal Agents
Amikacin Sulfate	2.3 mg/kg IM Q24 (1) (2)	Lemurs and other NHP
Amoxicillin	11 mg/kg PO BID (1) (2) (4) 11 mg/kg SC,IM SID (1) (2) (4) 7 mg/kg SC (2) 10 mg/kg PO (2)
Amphotericin B	0.25 - 1.0 mg/kg IV SID (1) (2) (4)
Ampicillin	20 mg/kg PO, IM, IV TID (1) (2) (4) 50 - 100 mg/kg IM BID x 7 - 10 days (1) (4) 30 mg/kg IM SID x 5 days (2) 5 mg/kg IM BID (2)
Cefazolin Sodium	25 mg/kg IM, IV BID x 7 - 10 days (1) (2) (4)
Cefotaxime Sodium	100 - 200 mg/kg IV Q6 - 8 hrs (1) (2) (4)	Great apes/Good CSF penetration.
Ceftazidime	50 mg/kg IM, IV Q8 (1) (2) (4)	Sifaka monkey (Propithecus sp.)
Ceftriaxone Sodium	50 - 100 mg/kg IM Q12 - 24h. (1) (4)
Cephalexin HCl	20 mg/kg PO ID (1) (2)
Chloramphenicol:	50 mg/kg PO BID (1) 50 - 100 mg/kg PO, SQ, IV TID(1) (4)
*succinate	20 mg/kg IM BID (1)
*succinate	25 mg/kg IV BID x10 days (2)
*succinate	50 mg/kg IM BID x10 days (2) 110 mg/kg IM QID for 5 - 10 days (2)	Pneumococcal meningoencephalitis (Streptococcus pneumoniae)
*palmitate	50 mg/kg PO BID (2)
Ciprofloxacin	250 mg/animal PO once, then 125 mg Q12 (1)	Rhesus macaques/ PD (5.1 - 13.0 kg)
Ciprofloxacin	16 - 20 mg/kg PO BID (1) (2) (4)	Based on PD dosage above; suspension of crushed tablets in sterile water
Doxycycline	60 mg/animal PO once, then 30 mg/kg BID (1)	Rhesus macaques/ PD (5.1 - 13.0 kg)
Doxycycline	3 - 4 mg/kg PO BID (1) 2.5 mg/kg PO BID (2) 5 mg/kg PO divided BID day one, then 2.5 mg/kg following days (4)	Based on PD dosage above.
Enrofloxacin	5 mg/kg PO, IM SID x10 days (1) 5 mg/kg PO, IM SID x 5 days (2) (4) 50 mg/kg SC BID (2)	Shigella flexneri → give PO injectable form
Erythromycin	75 mg/kg PO Q12 x 10 days (1) (2) (4) 5 mg/kg IM Q12 x 7 - 14 days (1) 40 mg/kg IM SID (2)	Campylobacter sp. diarrhea
Ethambutol HCl	22.5 mg/kg PO SID(1) (2)	Rhesus macaques/ mycobacteriosis; treat concurrently with isoniazid and rifampin; reduce to 15 mg/kg after 6 wks; cont. treatment for 1 year (1) In grape juice → reduce dose by 1/3 after 6 weeks (2)
Fluconazole	18 mg/kg PO Q24h (1) 2 - 3 mg/kg PO (2)	Swamp monkey (Allenopithecus nigroviridis)/systemic mycoses; treat concurrently with flucytosine; may be effective as sole agent (1)
Flucytosine	143 mg/kg PO SID(1)	Swamp monkey/systemic mycoses; treat concurrently with fluconazole
Furazolidone	5 mg/kg PO Q6h x 7 days(1) (4) 20 - 40 mg/kg PO Q6 (1) 10 - 15 mg/kg PO SID (2) 5 - 10 mg/kg PO (4)
Analgesics and Sedatives
Acepromazine Maleate	0.5 - 1.0 mg/kg IM, SQ, PO (2) (4) 0.2 mg/kg IM (2)
Acepromazine Maleate(A) and Buprenorphine HCl (B) mix	0.07 mg/kg (A) and 0.009 mg/kg (B) IM (2)
Acetaminophen	5 - 10 mg/kg PO (2) (4)
Aspirin	100 mg/kg PO SID (2) 20 mg/kg PO Q6 - 8 hours (2)
Banamine	2mg/kg BID
Buprenorphine HCl	0.01 mg/kg IM, IV Q12 hours (2) (4) 0.005 - 0.01 mg/kg IM, IV Q6 - 12 hours (2) 0.1 - 0.3 mg/kg IM Q6 - 12 hrs as needed (4)
Butorphanol Tartrate	0.01 mg/kg IV Q 3 - 4 hours (?) (2)
Carprofen	2 mg.kg PO
Chlorpromazine HCl	3 - 6 mg/kg IM (2) 1 - 6 mg/kg IM, PO (4)
Diazepam	1mg/kg IM, IV (2) 0.25 - 0.5 mg/kg IM, IV (4)
Fentanyl	0.05 - 0.10 mg/kg SC, IM (2)
Fentanyl/Droperidol(Innovar Vet)	0.1 - 0.2 mL/kg IM(2) 0.3 mL/kg IM (2) 1mL/ 10 - 20 kg IM, IV (sedative) (4) 0.11 mL/kg IM for anesthesia (4)
Ibuprofen	7mg/kg PO BID (5)
Ketamine HCl	5 - 40 mg/kg IM (2) (4)
	10 mg/kg IM (4)	plus Diazepam 7.5 mg/kg IM
	11 mg/kg IM (4)	plus Xylazine 0.5 mg/kg IM
Ketoprofen	2 mg/kg SID
Morphine Sulfate	1 - 2 mg/kg SC Q2 - 4 hours (2) 1 - 2 mg/kg IM, IV, SC, PO (4) 3 mg/kg SC (2)
Naproxen	10 mg/kg PO Q12 hrs (2) (4)
Oxymorphone HCl	0.15 mg/kg SC, IM, IV (2) (4)	Old World monkeys
Oxymorphone HCl	0.075 mg/kg SC, IM, IV (2) (4)	New World monkeys
Xylazine HCl	1 - 2 mg/kg IM (2)
Emergency Drugs
Atropine Sulfate	0.05 mg/kg IV (3)	Bradycardia
Dopamine HCl	10 mcg/kg/min IV (3)	Bradycardia after arrest in animals >3kg
Doxapram HCl	2 mg/kg IV (2)	Respiratory arrest
Epinephrine	0.2 - 0.4 mg/kg diluted in 5mL of sterile H2O endotracheally (3) 0.5 - 1.0 mL IV (3)	Cardiac arrest in animals > 2 kg both doses may be repeated every 3 - 5 minutes
Ephedrine	1.25 - 2.5 mg/kg IV (3)	Cardiac Arrest
Furosemide (Lasix)	1 - 2 mg/kg IV (3)	Pulmonary Edema
Lidocaine	1 - 2 mg/kg IV (3)	Premature Ventricular Contractions
Naloxone	0.1 - 0.2 mcg IV (3)	Opioid reversal
Norepinephrine Bitartrate	0.05 - 0.1 mcg/kg/min IV infusion (3)	Hypotension; prepare in a dextrose solution
Phenylephrine HCl	1 - 2 mcg/kg IV bolus, then 0.5 - 1.0 mcg/kg/min IV infusion (3)	Hypotension
Atipamazole HCl	0.2 mg IV, S. sciureus; 0.3 mg/kg IV, P. troglodytes (3)	Medetomidine reversal
Yohimbine		Xylazine reversal

These refer to the below references:

1. James W. Carpenter, Ted Y. Mashima, David J. Rupiper. Exotic Animal Formulary. Second Edition. W.B Sounders Company 2001

2. C. Terrance Hawk, Steven L. Leary. Formulary for Laboratory Animals. Second Edition. Iowa State University Press 1999.

3. Jeffrey D. Fortman, Terry A. Hewett, B. Taylor Bennett. The Laboratory Nonhuman Primate. CRC Press 2002.

4. Katherine E. Queensberry, Elizabeth V. Hillyer. The Veterinary Clinics of North America. Small Animal Practice. Exotic Pet Medicine II. January 1994. W.B. Saunders Company

5. APV Primate Formulary. Compiled by C.J. Doane and D. Rick Lee

While a sincere effort has been made to assure that all doses are accurate, errors may occur. The authors/publisher will assume no responsibility and should not be liable for any damages. It is suggested that the reader refer to the approved labeling information of any product. Additional dosing information regarding drug formulations for nonhuman primates is available through the Association of Primate Veterinarians (http://www.primatevets.org).

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References

1. Fortman JD, Hewett TA, Bennett BT. The Laboratory Nonhuman Primate. Boca Raton, FL: CRC Press, LLC, 2002. - Available from amazon.com -

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How to reference this publication (Harvard system)?

Linn, M. J. et al. (2006) “Biology and Medicine of Non-human Primates. Part II: Clinical Medicine and Uses”, Laboratory Animal Medicine and Management. Available at: https://www.ivis.org/library/laboratory-animal-medicine-and-management/biology-and-medicine-of-non-human-primates-part (Accessed: 11 September 2024).

Affiliation of the authors at the time of publication

^2,7Unit for Laboratory Animal Medicine and
^1,3,4,5,6Jobst Vascular Laboratory, Section of Vascular Surgery, Department of Surgery, University of Michigan Medical Center, Ann Arbor, MI, USA.

Author(s)

Linn M.J.

BGS

Jobst Vascular Laboratory, Section of Vascular Surgery, Department of Surgery, University of Michigan Medical Center

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Duran-Struuck R.

DVM

Transplantation Biology Research Center, Massachusetts General Hospital,

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Trivedi A.K.

Jobst Vascular Laboratory, Section of Vascular Surgery, Department of Surgery, University of Michigan Medical Center

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Zajic L.B.

Jobst Vascular Laboratory, Section of Vascular Surgery, Department of Surgery, University of Michigan Medical Center

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Wrobleski S.K.

Health Science Research Associate II

BS LVT LATG

Jobst Vascular Laboratory, Section of Vascular Surgery, Department of Surgery, University of Michigan Medical Center

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Hawley A.E.

Research Associate

MS

Jobst Vascular Laboratory, Section of Vascular Surgery, Department of Surgery, University of Michigan Medical Center

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Myers Jr. D.D.

Assistant Professor, Vascular Surgery Section / ULAM

DVM MPH

Unit for Lab Animal MED, Jobst Vascular Research Laboratories, University of Michigan Medical School

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Biology and Medicine of Non-human Primates. Part II: Clinical Medicine and Uses

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Table of Contents

Anesthesia, Analgesia, Euthanasia

Scheduled Drugs

Fasting Nonhuman Primates

Preanesthetic Medications

Inhaled Anesthetics

Anesthetic Emergencies

Analgesia for Nonhuman Primates

Euthanasia of Nonhuman Primates

Criteria for Euthanasia

Methods of Euthanasia

Diseases and Medicine

Viral Diseases of Nonhuman Primates

Adenovirus

Benign Epidermal Monkey Pox (poxvirus) - zoonotic

Callitrichid Hepatitis (Lymphocytic Choriomeningitis)

Cytomegalovirus

Dengue (Flavivirus)

Ebola And Marburg Virus - zoonotic

Encephalomyocarditis Virus

Hepatitis A - zoonotic

Hepatitis B - zoonotic

Hepatitis C

Hepatitis E

Herpes B Virus - zoonotic

Herpesvirus Papio 2

Herpesvirus Saimiri

Herpesvirus Simplex - zoonotic

Herpesvirus Tamarinus

Lymphocryptovirus

Measles (Rubeola Virus) - zoonotic

Molluscum Contagiosum (Molluscipoxvirus)

Monkeypox (Poxvirus) - zoonotic

Papillomavirus

Rhesus Lymphocryptovirus, Epstein-barr-like Viruses (EBV) - zoonotic

Simian Hemorrhagic Fever Virus

Simian Varicella Virus

Simian Virus 40 (SV40) - zoonotic

Yaba Pox Virus - zoonotic

Yellow Fever- zoonotic

Primate Retroviruses

Retroviruses - general information [256-258].

Primate Lentiviruses

Simian Immunodeficiency Virus (SIV)

Simian Type C Oncornaviruses

Simian T-Cell Leukemia Virus (STLV-1)

Simian Type-D Retroviruses

Bacterial Diseases of Nonhuman Primates

Bordetella

Campylobacter - zoonotic

Escherichia coli

Helicobacter

Klebsiella

Leprosy

Listeria

Moraxella catarrhalis

Nocardia

Pseudomonas

Yersinia

Salmonella - zoonotic

Shigella - zoonotic

Staphylococcus

Streptococcus pneumoniae

Tetanus

Tuberculosis (TB) (Mycobacterium) - zoonotic

Protozoan Parasites of Nonhuman Primates

Amoeba - zoonotic

Balantidium - zoonotic

Cryptosporidium - zoonotic

Encephalitozoon

Giardia - zoonotic

Hepatocystis

Malaria (Plasmodium)

Trypanosoma (Sleeping Sickness and Chaga’s Disease)

Metazoan Parasites of Nonhuman Primates

Acanthocephala (thorny headed worms)

Anatrichosoma