NONHUMAN PRIMATE DISEASES
BACTERIAL DISEASES | TUBERCULOSIS
Etiology: Mycobacterium tuberculosis, M. bovis.
Transmission: TB is rare in wild NHP populations that live far from humans, more common in monkeys with close human contact.
Direct contact, contact with respiratory or oral secretions, aerosols, ingestion, fomites.
Significance: More common in OWM that NWM. Rare in prosimians. NHP less resistant to disease than humans.
Clinical signs: Frequently asymptomatic until advanced. Can progess rapidly. CS include coughing, enlarged lymph nodes, splenomegaly, hepatomegaly, depression, wasting, inappetence, death.
Pathology: M. tuberculosis and M. bovis cause disseminated yellow-white granulomas in many organs, usually the lung, lymph nodes, spleen, and liver. Granulomas are characterized by caseous centers, macrophage giant cells, lymphocytes, and epitheliod cells. Acid fast stains may demonstrate bacilli in tissues.
Diagnosis: Intradermal TB testing. Mammalian Old Tuberculin (MOT) is injected intradermally in the upper eyelid. (15,000 units=0.1ml) and read at 24, 36, and 72 hours. Reaction is graded 1-5 (0-2 negative, 3 suspect, and 4 and 5 positive).
0: no reaction
1: bruise from injection, no palpebral swelling
2: variable erythema, no swelling
3: variable swelling, +/- erythema.
4: variable erythema with obvious swelling and drooping of eyelid
5: swelling and/or necrosis of eyelid, with eyelid closed (because of severe eyelid droop)
False negatives: immunodeficient, anergy, measles or measles vaccine
False positives: exposure to Freund’s Complete Adjuvant
During quarantine, NHP are tested every 2 weeks until at least 3 consecutive tests are negative. Maintenance colonies are tested every 3-6 months.
Other diagnostic tests: Culture of stomach washes (cough and swallow), lymph node, lung, liver, spleen. Growth requires 12 weeks.
PCR: human test, false negatives
Serology: false negatives
Radiographs not as effective as in humans, because pulmonary granulomas do not mineralize as readily as in humans.
Culture or PCR is required for speciation.
Treatment: Not normally recommeded. Euthanize all positive animals, as they are a health risk to other NHP and humans. Extremely rare or valuable animals may be treated with isoniazid, streptomycin, rifampin, ethambutol combinations. Probably only controls symptoms, rather than curing animal.
Zoonotic: Yes
MYCOBACTERIOSIS
Etiology: Atypical mycobacteria; M. avium, M. intracellulare, M. avium-intracellulare complex M. avium is a pathogen of birds. M intracellulare is an environmental saprophyte.
Transmission: Respiratory, oral, cutaneous
Clinical signs: CS for M. avium-intracellulare normally is seen only in immunodeficient animals. Diarrhea, weight loss, lymphadenopathy
Pathology: M. avium-intracellulare normally causes intestinal lesions, characterized by a thickened mucosa. Mesenteric lymph nodes are enlarged and yellow-white.
Diagnosis: MOT testing not reliable, even with M. avium antigen. PCR, Culture.
JOHNE’S DISEASE
Etiology: Mycobacterium paratuberculosis
Clinical signs: Chronic diarrhea and wasting
Pathology: Thickened intestinal mucosa, granulomatous inflammation of intestinal tract, enlarged mesenteric lymph nodes
SHIGELLOSIS
Etiology: Shigella flexneri (most), S. sonnei (some), other species less common.
Transmission: Fecal-oral
Significance:Not common in wild NHP; humans are the main source of infection for NHP colonies, with subclinical carriers maintaining it in the colony. Recovered animals frequently carriers, with relapse of CS subsequent to stress possible.
Clinical signs: Usually asymptomatic or mild in adults. CS more likely seen in young or immunocompromised or susceptible (never exposed) animals. CS include soft stool, fluid diarrhea, bloody, mucoid diarrhea that may contain shreds of mucosa. Weakness, recumbancy, facial edema, rectal prolapse, death.
Pathology: Colitis (not small intestine), with mucosal edema, hemorrhage, erosion, ulceration, necrosis, and pseudomembrane formation. Can also see necrotizing gingivitis, abortion, air sac infection. Histologic lesion is purulent, necrotizing colitis with crypt abscesses.
Diagnosis: CS, culture, lesions
Treatment: Supportive care, antibiotics
Prevention: Good sanitation
Zoonotic: Yes
CAMPYLOBACTERIOSIS
Etiology: Campylobacter fetus, jejuni, coli (Vibrio)
Transmission: Fecal-oral
Clinical signs: Asymptomatic carrier common; bloody diarrhea, dehydration, abortion.
Diagnosis: Pathology, culture (requires special media and low O2 atmosphere at 42° C)
Pathology: Small intestine and colon affected. Red, rough, edematous, mucosa hyperplasia, erosions; histologic silver stain reveals spiral bacteria in enterocytes.
Zoonotic: Yes
SALMONELLOSIS
Etiology: Salmonella enteriditis, typhimurium most common
Transmission: Fecal-oral. NHP frequently inoculated by rodent feces or human carrier
Clinical signs: Subclinical more common than clinically affected; diarrhea, similar to Shigellosis
Pathology: Small and large intestine affected, with shortened villi, crypt abscesses, edema. Signs similar to Shigellosis. Septicemia common, with bacteria and multifocal necrosis in liver, spleen, lungs
Diagnosis: CS, culture, lesions
Treatment: Antibiotics and supportive care
RESPIRATORY BACTERIAL DISEASES
Etiology: Most outbreaks associated with shipping, crowding , or other stress.
Clinical signs: Similar for all: bronchopneumonia with nasal discharge, air sac empyema, possible meningitis, encephalitis, death.
Bordetella bronchiseptica
Pasteurella multocida: more common in NWM
Klebsiella pneumoniae: OWM, NWM, apes
Streptococcus pneumoniae (diplococcus): more common in OWM, apes; frequently also causes meningitis in juveniles (primary cause of bacterial meningitis in NHP)
VIRAL DISEASES
HERPES B/ HERPESVIRUS SIMIAE/ CERCOPITHECINE HERPESVIRUS/ B VIRUS
Etiology: herpesvirus simiae (an alphaherpesvirus)
Transmission: Virus shed in oral and genital secretions, vesicular fluid. Transmitted by bite, scratch, direct contact, fomites, aerosol. Virus can be latent in sensory ganglia, reactivated with stress. No vertical transmission.
Species: Enzootic in asian macaques, not reported in african monkeys. Asian macaques are natural reservoir, so have life-long infection; estimates of percentage of monkeys in enzootic colony have virus varies 10-90%.
Clinical signs: Asymptomatic infections common in macaques; asymptomatic animals can shed virus. Vesicles on dorsum of tongue, lips, oral cavity which become ulcers and heal in 7-14 days; conjunctivitis. Rarely, cases have cutaneous lesions.
Severe disease in: Human, owl monkey, marmoset, african green monkey, gibbon, patas monkey, colobus monkey, capuchin monkey.
Pathology (non-macaques): Vesicles, focal necrosis in organs such as liver and kidney, encephalitis
Diagnosis: Lesions; serology (can get false negatives); virus culture (cotton swab of buccal mucosa and conjunctiva); PCR (negative not conclusive)
Treatment: NONE…dangerous zoonosis, so cull the monkey
Zoonosis: YES! Human and other susceptible species’ disease starts at site of inoculation (vesicles of skin, mucous membranes, conjunctivitis) and rapidly leads to encephalitis with necrosis. Most cases fatal, survivors may have permanent CNS damage, and require treatment with anti-viral medication for life.
Management: Assume all macaques are positive and shedding! Proper protection: double gloves, mask, eye protection. Do not handle unanesthetized monkeys. Thoroughly wash all wounds immediately(bleach or betadine scrub) Serum from monkey and human taken for serological baseline and follow-up.
HERPES SIMPLEX VIRUSES
Etiology: Herpes simplex virus, herpesvirus hominis type 1 (alphaherpesvirus)
Transmission: Humans are natural reservoir. Human to monkey and monkey to monkey transmission occurs. Latent or active infections.
Species: Chimpanzee, gibbon-mildly affected, usually local lesions; Owl monkey, tree shrew, lemur, marmoset, tamarin-susceptible to severe, generalized disease.
Clinical signs: Local or generalized lesions. Oral vesicles and ulcers in mildly affected species; conjunctivitis, encephalitis, death in severely affected species
Pathology: Oral, genital ulcers; conjunctivitis; keratitis; meningoencephalitis with necrosis; focal necrosis in visceral organs. Inclusion bodies are intranuclear and eosinophilic.
MEASLES (RUBEOLA)
Etiology: Human measles virus; F: paramyxoviridae, genus: morbillivirus, related to canine distemper, rinderpest
Transmission: Aerosol. Measles is not a natural disease of NHP, but is acquired through contact with humans. Once in a colony, spreads from NHP to NHP.
Species: Apes, macaques, baboons, african green monkeys, owl monkey, squirrel monkeys, marmosets, tamarins.
Clinical signs: Vary with species. OWM tend to get interstitial pneumonia, NWM tend to get ulcerative enterocolitis. Immunosuppression, maculopapular rash, conjunctivitis, facial erythema, respiratory signs, diarrhea, and abortion (rare). Can be fatal, especially in owl monkey, squirrel monkey, marmoset, tamarin (fatal gastoenterocolitis). Macaques have mild disease, with fever, rash that becomes a dermatitis, possible Koplik spots (white foci with raised, red rim = focal necrosis on oral mucosal membranes), respiratory signs.
Pathology: interstitial pneumonia with syncytial cells (giant cell pneumonia); syncytial cells also in skin, lymph nodes; lymphoid depletion; enterocolitis. Inclusion bodies are intranuclear and cytoplasmic, eosinophilic, and are seen in lung, gi epithelium.
Treatment: Supportive care, antibiotics for secondary bacterial infections
Management: MLV measles vaccine (human or canine)(chick embryo) can be used. Animals raised in closed colonies likely to be susceptible (never exposed). Previously exposed animals probably don’t need vaccine. Infection with measles virus or vaccination can cause false negative on TB intradermal test (immune function altered)
Zoonosis: Yes
SIMIAN IMMNODEFICIENCY VIRUS (SIV)
Etiology: Family: Retroviridae, genus:Lentivirus
There are genomically different isolates. SIV, found in different NHP species. These viruses are related to HIVs (also lentiviruses). HIV-2 is genomically closer to the SIVs than HIV-1.
Species: Macaques: The natural host of the SIV macaque isolates is unknown, but is not believed to be macaques, because prevalence is low in captives, and SIV has not been found in wild macaques.
Non-macaques: SIV has been isolated from african green monkeys, with prevalence high in wild animals. Assumed to be natural host, with persistent, asymptomatic infection. SIV has been isolated from mangabys, with high prevalence in captive, but not wild, animals. Probably not the natural host. SIV has been isolated from mandrills, gabon.
Clinical signs: Macaques SIV is pathologic only in macaques. Virulence varies with isolate. Immunodeficiency is the main consequence, although the infection begins with a rash and lymphadenopathy. Lymphoid depletion follows, with immunodeficiency and opportunistic infections (Cytomegalovirus, Candida, Mycobacterium avium/intracellulare, Cryptosporidiosis, Pneumocystis, Trichomoniasis, Toxoplasmosis, Aspergillosis). Lesions thought to be directly caused by the virus include rash, lymphoid hyperplasia and depletion, pneumonia, encephalitis, glomerulosclerosis. Other clinical signs include wieght loss, diarrhea, anemia, thrombocytopenia, neoplasia.
Zoonosis:? SIV should be considered a potential zoonotic disease. Humans have seroconverted to SIV, and there has been 1 case of virus isolation from a human. However, there has been no known case of disease in a human (CDC 1992).
SIMIAN RETROVIRUS (SRV)
Etiology: Family: retroviridae Betaretrovirus, D-Type virus
Transmission: Contact, bite, scratch, grooming, perinatal, vertical
Species: Common in macaques, both wild and captive
Clinical signs: Disease only in macaques. Can be asymptomatic for a long time, then SAIDS. Immunosuppression is main clinical problem. Peripheral lymphadenopathy (early); splenomegaly; weight loss; fever; peristent diarrhea; opportunistic and chronic, refractory infections; retroperitoneal and subcutaneous fibromatosis; pancytopenia; lymph node lesions (depletion); bone marrow hyperplasia; NOMA (necrotizing gingivitis).
Diagnosis: Cell culture, PCR, Serology, In situ hybridization. Animals can be viremic and shedding and have negative serology.
Zoonotic: No
EBOLA RESTON / SIMIAN EBOLA-LIKE FILOVIRUS
Etiology: Family: Filoviridae, genus: filovirus, sp: Marburg and Ebola. Ebola has 4 serotypes: reston, sudan, zaire, cote-d’Ivoire. Vary in pathogenicity.
Transmission: Aerosol, direct contact, fomites
Clinical signs: Fatal in macaques, occurs in many monkeys imported from africa and asia. CS include fever; weight loss; anorexia; hemorrhage; petechia on face, chest, limbs; diarrhea; severely elevated LDH. Carried asymptomatically in african monkeys like patas.
Pathology: Maculopapular rash; splenomegaly; petechial hemorrhages; doudenal hemorrhage; interstitial pneumonia; lymphoid, adrenal cortex, lung, and liver necrosis; fibrin in spleen; inclusion bodies are amphophilic, cytoplasmic in many tissues, such as liver, adrenal gland, spleen.
Management: Don’t house macaques with patas or other african NHPs.
Zoonosis: Yes, although Ebola Reston much less pathogenic to humans that other Ebolas.
SIMIAN HEMORRHAGIC FEVER VIRUS (SHFV)
Etiology: Family: Arterivirus
Transmission: Endemic and asymptomatic in patas monkey and other african monkeys (african green m, baboons). Transmitted to macaques requires parentaral exposure to body fluids and tissues. Among macaques, it is transmitted through contact, fomites, or aerosol.
Clinical signs: Epidemics with nearly 100% morbidity and mortality in macaques. CS: acute disease, with fever, anorexia, lethargy, facial edema, rash, hemorrhage (cutaneous, subcutaneous, epistaxis), DIC, thrombocytopenia, diarrhea.
Pathology: Gross lesions may be absent. Petechial hemorrhage on mucosal and serosal surfaces, hemorrhage of the proximal duodenum, splenomegaly, splenic lymphid follicles are ringed with a zone of hemorrhage, multi-organ necrosis (spleen, gi tract, lung, brain, less in liver), vasculitis and hemorrhage, intravascular fibrin (DIC), fibrin in slpeen, lymphohistiocytic meningoencephalitis.
Zoonosis: No
MONKEY POX
Etiology: Genus: orthopoxvirus (related to smallpox-variola virus)
Transmission: Contact, wounds
Species: OWM, NWM
Clinical signs: Cutaneous lesions: papules which progress to vesicles, then become umbilicated with a necrotic center. Eventually they slough, leaving a scar. Most infections only cause skin lesions, a few lead to multi-organ necrosis and death.
Inclusion bodies are intracytoplasmic
Zoonotic: Yes (report to CDC)
TANAPOX VIRUS/ BEMP/ BENIGN EPIDERMAL MANKEY POX
Etiology: Genus: yatapoxvirus
Transmission: Contact
Species: Macaques
Clincal signs: Small red papules progress to raised plaques (0.5-1.5 cm), usually on head and limbs; eventually ulcerate, become umbilicated, often with red border. Eventually heal without scarring in 4-6 weeks. Infection leads to immunity.
Zoonotic: Yes (with fever)
YABA MONKEY POX VIRUS
Etiology: Genus yatapoxvirus
Transmission: Mosquito vector (or needles)
Species: Human, macaque, baboon
Clinical signs: Benign histiocytoma, subcutaneous nodules (up to 4 cm) on head, limbs which ulcerate and then heal without scarring in 6-12 weeks. Infection leads to immunity.
Zoonotic: Yes
MOLLUSCUM CONTAGIOUSUM
Etiology: Genus: molluscipoxvirus
Transmission: Unknown
Species: NHP, human, other mammals
Clinical signs: Smooth, pink papules with waxy, umbilicated core, around face and eyes, groin; 1 or multiple. Eventually necroses and heals.
Zoonotic: Yes
PARASITIC DISEASES
RESPIRATROY MITES
Etiology: Pneumonyssus simicola (lungs)
Transmission: Close contact suspected; exact mechanism unknown; eggs inhaled?
Species: Wooly monkey, howler monkey, macaques, chimpanzee, langur, proboscis monkey
Clinical signs: Usually subclinical; respiratory disease with cough and dyspnea.
Pathology: Yellow (1-10mm) air filled cysts (mite houses: with mostly females, eggs, larvae, few males) in lung parenchyma, or on pleural surface, in which case they are raised. Bronchial lymph nodes are pigmented, with a mottled light and dark appearance, due to mite pigment deposition. Microscopic lesions are of are chronic bronchiolitis, bronchiectasis, granulomatous inflammation. Mite pigment is deposited surrounding the inlammation, is golden brown, and is refractile under polarized light.
Diagnosis: Tracheobronchiolar lavage; necropsy
Treatment: IVM
Etiology: Rhinophaga spp (nasal cavity)
Transmission: Unknown
Species: OWM, apes
Clinical signs: Usually none, mucosal polyps and inflammation
STRONGYLOIDES
Etiology: S. cebus (NWM) S. fulleborni and S. stercoralis (OWM, apes)
Transmission: Oral or skin penetration by 3rd stage larva (skin penetrators migrate through lungs, and are then swallowed to reach gi tract). Complex life cycle, with both parasitic and free-living forms. Adults females burrow into the mucosa of the proximal small intestine and deposit ova. Larvae hatch, enter lumen, develop into 1st stage larvae and pass in feces. Larvae develop into 3rd stage in environment within 24 hours. In autoinfection, the larvae penetrate the colon before passing in feces, causing colitis.
Clinical signs: Ulcerative, hemorrhagic enterocolitis; granulomas in small intestine where larvae hatch out, pulmonary hemorrhage with lung migration.
Diagnosis: Baerman; necropsy
Treatment: Thiabendazole, possibly IVM
PINWORMS
Etiology: Enterobius sp (OWM, apes), Trypanxyuris sp and Oxyuronema sp (NWM)
Transmission: Oral, adults mature in cecum/colon
Clinical signs: Excoriating pruritis as eggs are deposited at anus; can aggravate other enteric disease
Diagnosis: Tape test; ova are banana shaped, similar to Syphacia
Zoonotic: Yes
AMEBIASIS
Etiology: Entamoeba histolytica (phylum sarcomastigophora)
Transmission: Oral
Species: OWM, NWM, apes
Clinicla signs: Usually asymptomatic carriers, can cause diarrhea (sometimes hemorrhagic), weight loss, lethargy, anorexia, vomiting.
Pathology: Flask shaped ulcers in gi mucosa and muscularis; granulomatous, ulcerative colitis; may spread via blood vessels to form abscesses in lungs, liver, brain.
Diagnosis: sucrose gradient fecal float to find cysts; PCR
Treatment: Metranidazole
Zoonosis: Yes (human amoebic dysentery)
BALANTIDUIM
Etiology: Balantidium coli (phylum ciliophora)
Transmission: Oral
Species: OWM, NWM, apes
Clinical signs: Usually asymptomatic, can cause diarrhea, weight loss, lethargy, tenesmus and rectal prolapse; probably opportunistic in all but apes
Pathology: Apes-ulcers in gi tract, occasional necrosis and hemorrhage
Diagnosis: Necropsy
Treatment: Metranidazole
Zoonosis: May cause diarrhea in humans
MISCELLANEOUS DISEASES
ENDOMETRIOSIS
Etiology: Proliferation of ectopic endometrial tissue; mechanism unknown, may be due to retrograde menstruation, uterine surgery.
Clinical signs: Abdominal swelling and pain, uremia, constipation, anemia.
Pathology: Multiple cysts with chocolate brown fluid, fibrosis, hemosiderosis; Lower abdominal and pelvic organs frequently adhered into a single mass, with secondary obstruction of intestine or ureters.
Diagnosis: Necropsy
PERIODONTAL DISEASE
Etiology: Frequently occurs with Shigellosis and Simian Retrovirus SAIDS (NOMA, cancrum oris); associated with a balance of the normal oral flora due to malnutrition, immunosuppression, debilitation due to infectious disease.
Clinical signs: Slight reddening of gums to necrotizing ulcerative gingivitis with gingival bleeding; gangrenous necrosis of alveolar bone in SRV NOMA.
ACUTE GASTRIC DILATATION (BLOAT)
Etiology: Multifactorial; food restriction, overeating, anesthesia; Clostridium perfringens is isolated, and may be resonsible for gas production
Clinical signs: Usually occurs in caged monkeys; usually found dead; swollen and taut abdomen; death is due to respiratory distress, impaired venous return, shock.
Pathology: Stomach distended with gas and brown fluid, intestine congested, stomach rupture can lead to subcutaneous emphysema.
TRAUMA
Etiology: Fighting, especially when new individuals are introduced into a group situation or during breeding season. Common in rhesus macaques.
Clinical sings: Lacerations, bruises, abrasions, punctures, crush injuries to face or extremities. Injuries to the underlying soft tissue are frequently more extensive that they appear. Also, bite wounds are frequently worse than they appear. Bacterial contamination and damage to blood vessels can lead to gangrene necrosis.
Pathology: Muscle necrosis, gangrene, myoglobinuric nephrosis, hyperkalemia
Treatment: If an animal is in shock: IV fluids and steroids, antibiotics.
SELF TRAUMA
Etiology: Psychological disorder, frequently occurs with singly housed animals. Linked to opiod release.
Clinical signs: Bite wounds to arms and legs, hands; removing of hair.
Treatment: Environmental enrichment. Group housing if appropriate; puzzle feeders, toys, videos; drug therapy if necessary.
VITAMIN C DEFICIENCY /SCURVY
Etiology: NHP (and HP and some other species) are not able to synthesize Vitamin C, due to a lack of an enzyme (L-gulonolactone oxidase). Require dietary Vitamin C.
Clinical signs: Epiphyseal fractures (rhesus), cephalohematomas (squirrel monkey), anemia, subperiosteal hemorrhage, abnormal ossification of bones (wide zone of unossified cartilage).
Pathology: Lack of vitamin C leads to an inability to form normal collagen, which affects blood vessels and bone, primarily.
Treatment: Vitamin C
Prevention: Commercial monkey chows with Vitamin C, supplement diet with fruits, vegetables.
VITAMIN D3 DEFICIENCY /SIMIAN BONE DISEASE
Etiology: NWM cannot utilize vitamin D2 (plant source), and need vitamin D3 in diet. Ca:P imbalance from feeding excessive fruit may contribute.
Clinical signs: Distorted limbs, kyphosis, pathologic fractures, decreased bone density.
Treatment: Diet fortified with Vitamin D3.
Prevention: Feed NW monkey chow, UV light exposure.
HYPERTROPHIC CARDIOMYOPATHY
Etiology: Uunkown
Species: Owl monkey, squirrel monkey, marmoset, apes, macaques
Clinical signs: Squirrel monkey and marmoset: ascites, CHF, hypertension, posterior paralysis. Apes: associated with obesity in middle aged and older, usually no CS, just acute death. Macques: associated with old age, frequently no CS.
Pathology: NWM: cardiomegaly, myocardial hypertrophy, fibrosis, atrial thrombosis, saddle thrombus in aorta, ascites, pulmonary edema. Owl monkey also gets atherosclerosis, and is used for a disease model for human cardiomyopathy and hypertension. Apes: myocardial hypertrophy and fibrosis
MARMOSET COLITIS/ WASTING SYNDROME
Etiology: Undetermined, believed to be related to low protein diet. It is difficult to get them to consume adequate protein/calories.
Clinical signs: Weight loss, muscle atrophy, hair loss, hypoproteinemia with ventral abdominal edema, anemia, hypoglycemic episodes, chronic colitis or megacolon.
Treatment: Supplement diet. Marmoset Jelly (Purina): high protein supplement
