Etiology: Mycobacterium tuberculosis, M. bovis, M. avium, M. paratuberculosis, atypical mycobacteria.

Transmission: Respiratory, oral. M. tuberculosis and M. bovis are typically acquired from infected humans or ruminants in the country of origin. Tuberculosis is rare in wild populations. M. avium is a natural pathogen of birds and M. intracellulare is a common environmental saprophyte.

Clinical: Tuberculosis in monkeys, especially rhesus, is a rapidly progressive disease, and seldom becomes arrested as in humans. New World monkeys generally more resistant than OWM. Often there are no clinical signs in caged monkeys. Severely affected monkeys may show coughing, wasting, enlarged lymph nodes, splenomegaly, and hepatomegaly. With modern management, most likely to diagnose by tuberculin testing. Follow CDC guidelines for testing and diagnosis in quarantine (MMWR 42/#29, 1993). For testing, use Mammalian Old Tuberculin, 1,500 units (some recommend 3,000 units) intradermally in upper eyelid. Read at 24, 48, & 72 hrs. for swelling. Monkeys which have been inoculated with Freund's Complete Adjuvant are often tuberculin positive. Orangutans have a high incidence of false positive tuberculin reactions.

Monkeys with M. avium/intracellulare may be weakly positive with OT, but are usually more strongly positive when tested with tuberculin from M. avium. These animals are usually immunodeficient and have a history of diarrhea and chronic wasting.

M. paratuberculosis infection has only been confirmed in Macaca arctoides. These animals have diarrhea and wasting.

Pathology: M. tuberculosis & M. bovis cause disseminated yellow-white granulomas in the lung, lymph nodes, spleen, liver, and other organs. Typical lesions are tuberculoid granulomas characterized by caseous centers, giant cells, lymphocytes and epithelioid cells. AFB may be difficult to find, and are best sought in the caseous center. Often many sections must be examined to confirm the diagnosis. The auramine-rhodamine fluorescent stain is very useful if AFB are sparse. Culture or PCR is necessary to identify the species of mycobacteria.

M. avium & M. paratuberculosis typically cause intestinal lesions characterized by a firm thickened mucosa due to a diffuse histiocytic infiltrate in the lamina propria and abundant AFB. Mesenteric lymph nodes are enlarged and yellow white. Epithelioid change, caseation, and giant cells are not usually features of lesions caused by these bacteria, although tubercles have rarely been reported. M. avium-intracellularae infections are associated with immunodeficiency and are seen in acquired immunodeficiency syndromes in macaques infected with SRV and SIV.

Fourie PB, et al. Mycobacterium tuberculosis in a closed colony of baboons. Lab Anim 17:125-128, 1983.

Zumpe D, et al. Unusual outbreak of tuberculosis due to Mycobacterium bovis in a closed colony of rhesus monkeys. Lab Anim Sci 30:237-240, 1980.

Typhonas L, et al. Pott's paraplegia in a tuberculous rhesus monkey. J Med Primatol 11:211-220, 1982.

Fox JG, et al. A comparison of two tuberculins in nonsensitized macaques. J Med Primatol 11:380-388, 1982.

Smith ED. Avian tuberculosis in monkeys. Am Rev Resp Dis 107:469-471, 1973.

Fleischman RW, et al. Nontuberculous mycobacterial infection attributable to Mycobacterium intracellularae serotype 10 in two rhesus monkeys. JAVMA 181:1358-1362, 1982.

Holmberg CA, et al. Nontuberculous mycobacterial disease in rhesus monkeys. Vet Pathol 19(suppl. 7):9-16, 1982.

Soave O, et al. Atypical mycobacteria as the probable cause of positive tuberculin reactions in squirrel monkeys. Lab Anim Sci 31:295-296, 1981.

McClure HM, et al. Mycobacterium paratuberculosis infection in a colony of stumptail macaques. J Infect Dis 155:1011-1019, 1987.

Sapolsky RM, et al. Bovine tuberculosis in a wild baboon population: Epidemiological aspects. J Med Primatol 16:229-235, 1987.

Wolf RH, et al. Multidrug chemotherapy of tuberculosis in rhesus monkeys. Lab Anim Sci 38:25-33, 1988.

Bellinger DW, et al. Cutaneous Mycobacterium avium infection in a Cynomolgus monkey. Lab Anim Sci 38:85-86, 1988.

Goodwin BT, et al. Unusual lesion morphology and skin test reaction for Mycobacterium avium complex in macaques. Lab Anim Sci 38:20-24, 1988.

Pierce DL, et al. Misleading positive tuberculin reactions in a squirrel monkey colony. Lab Anim Sci 38:729-730, 1988.

Renquist DM, et al. Tuberculosis in nonhuman primates. An overview. IN: Montali RJ (ed). Mycobacterial infections of zoo animals. Smithsonian Press, Washington, DC, 1978 pp9-16.

Holmberg CA, et al. Immunologic abnormality in a group of Macaca arctoides: high mortality due to atypical mycobacterial and other disease processes. Am J Vet Res 46:1192-1196, 1985.

King NW. Mycobacterium avium-intracellulare infection. In: Jones TC, et al. (eds) Monographs on Pathology of Laboratory Animals: Nonhuman Primates I, Springer-Verlag, 1993, 57-63.

King NW. Tuberculosis. In: Jones TC, et al. (eds) Monographs on Pathology of Laboratory Animals: Nonhuman Primates I, Springer-Verlag, 1993, 141-148.

Anderson DC, et al. Paratuberculosis, Nonhuman primates. In: Jones TC, et al. (eds) Monographs on Pathology of Laboratory Animals: Nonhuman Primates I, Springer-Verlag, 1993, 148-154.

Benson CA, et al.Mycobacterium avium complex infection and AIDS: Advances in theory and practice. Clin Inf Dis 17:7-20, 1993.

CDC. Tuberculosis in imported nonhuman primates-United States, June 1990-1993. MMWR 42:No. 29: 672-677, 1993.

Centers for Disease Control. Guidelines for preventing the transmission of Mycobacterium tuberculosis in health-care facilities. MMWR 43:33-34, 1994.

Rock FM, et al. Diagnosis of a case of Mycobacterium tuberculosis in a cynomolgus (Macaca fascicularis) monkey colony by polymerase chain reaction and enzyme-linked immunosorbent assay. Lab Anim Sci 45:315-319, 1995.

Brammer DW, et al. Mycobacterium kansasii infection in squirrel monkeys (Saimiri sciureus sciureus). J Med Primatol 24:231-235, 1995.

Hines ME, et al. Mycobacterial infections of animals: pathology and pathogenesis. Lab Anim Sci 45:334-351, 1995.

Etiology: Mycobacterium leprae

Transmission: Respiratory, skin?

Clinical: Nodular thickening of skin and peripheral nerves. Paralytic deformity of hands and feet. Natural infections in chimpanzee and sooty mangabey (Cercocebus torquatus atys).

Pathology: Leprosy is a pathologically complex disease that has a spectrum of lesions that depend on the degree of cell mediated immunity the host is able to mount against M. leprae. Natural infections in nonhuman primates have taken the lepromatous form, indicating no CMI. Lesions occur predominantly in the skin and peripheral nerves, particularly in cooler areas (ears, tail, scrotum). Histiocytic infiltrate with variable numbers of lymphocytes and plasma cells in skin and nerves. Acid-fast bacilli demonstrable with Fite-Faraco acid fast stain. Nerve lesions are pathognomonic.

Donham KJ, et al. Spontaneous leprosy-like disease in a chimpanzee. J Infect Dis 136:132-136, 1977.

Leininger JR, et al. Leprosy in a chimpanzee: Postmortem lesions. Int J Lepr 48:414-421, 1980.

Meyers WM, et al. Leprosy in a mangabey monkey - naturally acquired infection. Int J Lepr 53:1-14, 1985.

Baskin GB, et al. Experimental leprosy in the mangabey (Cercocebus atys): Necropsy findings. Int J Lepr 53:269-277, 1985.

Martin LN, et al. Experimental leprosy in nonhuman primates. Adv Vet Sci Comp Med 28:201-236, 1984.

Baskin GB. Leprosy. In: Jones TC, et al. (eds) Monographs on Pathology of Laboratory Animals: Nonhuman Primates II, Springer-Verlag, 1993, 8-14.

Etiology: Shigella flexneri, S. sonnei, others are less common.

Transmission: fecal-oral.

Clinical: Variable. Asymptomatic carriers are common. May have soft stool, fluid diarrhea, or more commonly, the bloody mucoid diarrhea of classical dysentery. Monkeys with colitis due to Shigella will rapidly dehydrate and die unless treated promptly and vigorously. Shigella affects only primates. Clinical disease is often precipitated by stress.

Pathology: The lesions of shigellosis are limited to the colon, may be focal or diffuse, and are characterized by edema, hemorrhage, erosion & ulceration, and pseudomembrane formation. Microscopically the lesion is purulent, necrotizing colitis, often with crypt abscesses. Shigella occasionally causes periodontitis in monkeys. The diagnosis must be confirmed by culture.

Mulder JB, et al. Shigellosis in nonhuman primates: a review. Lab Anim Sci 21:734-738, 1971.

Good RC, et. al. Enteric pathogens in monkeys. J Bacteriol 97:1048-1055, 1969.

Cooper JE, et al. An outbreak of shigellosis in laboratory marmosets and tamarins. J Hyg 76:415-424, 1976.

Pucak GJ, et al. Elimination of the Shigella carrier state in rhesus monkeys (Macaca mulatta) by trimethoprim-sulfamethoxazole. J Med Primatol 6:127-132, 1977.

Armitage GC, et al. Periodontal disease associated with Shigella flexneri in rhesus monkeys. J Periondontal Res 17:131-144, 1982.

Fincham JE, et al. Endemic enteric disease in vervet monkeys. J S African Vet Assoc 52:177-179, 1981.

Rout WR, et al. Pathophysiology of Shigella diarrhea in the rhesus monkey: intestinal transport, morphological, and bacteriological studies. Gastroenterol 68:270-278, 1975.

Hirsh DC, et. al. Microscopic examination of stools from nonhuman primates as a way of predicting the presence of Shigella. J Clin Micro 11:65-67, 1980.

Ogawa H, et. al. Shigellosis in cynomolgus monkeys. Jap J Med Science & Biol 17:321-332, 1964.

Lemer R, et. al. Marasmus & shigellosis in two infant gorillas. J Med Primatol 3:365-369, 1974.

Takeuchi A, et. al. Experimental acute colitis in the rhesus monkey following peroral infection with Shigella flexneri. Am J Pathol 52:503-512, 1968.

Olson LC. Control of Shigella flexneri in Celebes black macaques (Macaca nigra). Lab Anim Sci 36:240-242, 1986.

Dinari G, et. al. Local and systemic antibody to Shigella flexneri in rhesus monkeys. J Infect Dis 155:1065-1069, 1987.

Keusch GT, et al. Shigellosis: recent progress, persisting problems, and research issues. Pediatr Infect Dis J 8:713-719, 1989.

Russel RG, et al. Shigellosis. In: Jones TC, et al. (eds). Monographs on pathology of laboratory animals: Nonhuman primates II. Springer-Verlag, 1993, 46-53.

Black-Schultz L, et al. Lack of reactivation of shigellosis in naturally infected enrofloxacin-treated cynomolgus monkeys after exogenous immunosuppression. Lab Anim Sci 47:602-605, 1997.

Wolfensohn S. Shigella infection in macaque colonies: Case report of an eradication and control program. Lab Anim Sci 48:330-333, 1998.

Etiology: Salmonella enteritidis, S. typhimurium

Transmission: fecal-oral, rodent feces most common source.

Clinical: Can carry asymptomatically. Sporadic or epizootic. Watery to bloody, mucoid diarrhea. May become moribund and die.

Pathology: Necrotizing, suppurative enterocolitis. May become septicemic resulting in pyogranulomas in liver and other organs. Resembles shigellosis, but Shigella does not become septicemic and does not affect the small intestine.

Takasaka M, et al. An outbreak of salmonellosis in newly imported cynomolgus minkeys. Jpn J Med Sci Biol 41:1-13, 1988.

Thurman J, et al. Septic abortion caused by Salmonella heidelberg in a white-handed gibbon. J Am Vet Med Assoc 183:1325-1326, 1983.

Ocholi RA, et al. Fatal case of salmonellosis (Salmonella pullorum) in a chimpanzee (Pan troglodytes) in the Jos Zoo. J Wildl Dis 23:669-70, 1987.

Klumpp SA, et al. Salmonella osteomyelitis in a rhesus monkey. Vet Pathol 23:190-197, 1986.

Fox JG. Transmissible drug resistance in Shigella and Salmonella isolated from pet monkeys and their owners. J Med Primatol 4:165-171, 1975.

Kent TH, et al. Salmonella gastroenteritis in rhesus monkeys. Arch Pathol 8:279, 1966.

Kourany M, et al. A subcutaneous abscess associated with Salmonella typhimurium in a black howler monkey (Alouatta villosa). Lab Anim Sci 21:412-414, 1971.

Rout WR, et al. Pathophysiology of Salmonella diarrhea in the rhesus monkey: Intestinal transport, morphological and bacteriological studies. Gastroenterol 67:59-70, 1974.

Gaines S, et al. Studies on infection and immunity in experimental typhoid fever. VII. The distribution of Salmonella typhi in chimpanzee tissue following oral challenge, and the relationship between numbers of bacilli and morphologic lesions. J Infect Dis 118:293-306, 1968.

Etiology: Campylobacter (Vibrio) fetus ss. jejuni, coli

Transmission: Oral

Clinical: Asymptomatic carriers are common. Diseased monkeys have fluid, sometimes bloody diarrhea and dehydration. Campylobacter has been associated with abortions in primates. Isolation requires special media and atmosphere.

Pathology: Small intestine and colon reddened, roughened, edematous. Histology in colon can be similar to shigellosis, but is usually much less severe and can also affect small intestine. Colonic mucosa sometimes hyperplastic. Can demonstrate spiral bacteria with silver stains.

Tribe GW, et al. Clinical significance of Campylobacter fetus in primates. Primate Supply 6:9-14, 1981.

Tribe GW, et al. Biphasic enteritis in imported cynomolgus monkeys infected with Shigella, Salmonella, and Campylobacter species. Lab Anim 17:65-69, 1983.

Bryant JL, et al. Campylobacter jejuni isolated from patas monkeys with diarrhea. Lab Anim Sci 33:303-305, 1983.

Morton WR, et al. Identification of Campylobacter jejuni in Macaca fascicularis imported from Indonesia. Lab Anim Sci 33:189-191, 1983.

Fox JG. Campylobacteriosis - a new disease in laboratory animals. Lab Anim Sci 32:625-637, 1982.

Tribe GW., et al. Campylobacter in monkeys. Vet Rec 106:365-366, 1980.

Fitzgeorge RB, et al. Experimental infection of rhesus monkeys with a human strain of Campylobacter jejuni. J Hyg, Camb 86:343-351, 1981.

Goodman LJ, et al. Effects of erythromycin and ciprofloxacin on chronic fecal excretion of Campylobacter species in marmosets. Antimicrobial Agents Chemother 29:185-187, 1986.

Russell RG, et al. Early colonic damage and invasion of Campylobacter jejuni in experimentally challenged infant Macaca mulatta. J Inf Dis 168:210-215, 1993.

Russell RG. Campylobacter jejuni colitis. In: Jones TC, et al. (eds). Monographs on pathology of laboratory animals: Nonhuman primates II. Springer-Verlag, 1993, 71-75.

Etiology: Helicobacter pylori

Transmission: Oral

Clinical: None usually, occasional vomiting. Prevalent in rhesus stomachs.

Newell DG, et al. Naturally occurring gastritis associated with Campylobacter pylori infection in the rhesus monkey. Lancet ii:1338, 1987.

Bronsdon MA, et al. Campylobacter pylori isolated from the stomach of the monkey, Macaca nemestrina. J Clin Microbiol 26:1725-1728, 1988.

Baskerville A, et al. Naturally occurring chronic gastritis and C. pylori infection in the rhesus monkey: a potential model for gastritis in man. Gut 29:465-472, 1988.

Reed KD, et al. Campylobacter-like organisms in the gastric mucosa of rhesus monkeys. Lab Anim Sci 38:329-331, 1988.

Fox JG, Lee A. Gastric Campylobacter-like organisms: Their role in gastric disease of laboratory animals. Lab Anim Sci 39:543-553, 1989

Curry A, et al. Spiral organisms in the baboon stomach. Lancet Sept 12, 1987, 634-5.

Euler AR, et al. Evaluation of two monkey species (Macaca mulatta and Macaca fascicularis) as possible models for human Helicobacter pylori disease. J Clin Microbiol 28:2285-2290, 1990.

Bronsdon MA, et al. Helicobacter nemestrinae sp. nov., a spiral bacterium found in the stomach of a pigtailed macaque (Macaca nemestrina). Int J System Bacteriol 41:148-153, 1991.

Dubois A, et al. Gastric injury and invasion of parietal cells by spiral bacteria in rhesus monkeys. Gastroenterol 100:884-891, 1991.

Curry A, et al. Sprial organisms in the baboon stomach. Lancet 2:96, 1987.

Masubuchi N, et al. Experimental infection of the cynomolgus monkey with Helicobacter pylori. Nippon Rinsho 51:3127-3131, 1993.

Takahashi S, et al. Serial change of gastric mucosa after challenging with Helicobacter pylori in the cynolmogus monkey. Int J Med Microbiol Virol Parasitol Infect Dis 280:51-17, 1993.

Doenges JL. Spirochetes in the gastric glands of Macaccus rhesus and man without related disease. Arch Pathol 27:469, 1939.

Handt LK, et al. Evaluation of two commercial serologic tests for the diagnosis of Helicobacter pylori infection in the rhesus monkey. Lab Anim Sci 45:613-617, 1995.

Stadtländer CTK-H, et al. Experimentally induced infection with Helicobacter pylori in squirrel monkeys (Saimiri spp.): Clincial, microbiological, and histopathologic findings. Lab Anim Sci 48:303-309, 1998.

Reindel JF, et al. An epizootic of lymphoplasmacytic gastritis attributed to Helicobacter pylori infection in cynomolgus monkeys (Macaca fascicularis). Vet Pathol 36:1-13, 1999.

Etiology: Gastrospirillum hominis-like organisms, also called Helicobacter heilmannii.

Oliva MM, et al. Gastritis associated with Gastrospirillum hominis in children. Comparison with Helicobacter pylori and review of the literature. Mod Pathol 6:513-515, 1993.

Handt L. Personal communication. Merck Research Laboratories, West Point, PA 19486.

Etiology: Streptococcus (Diplococcus) pneumoniae.

Transmission: Respiratory.

Clinical: Tends to occur in small focal outbreaks. Often found dead, but may have signs of pneumonia, meningitis, arthritis, depression, dehydration. Growth in culture is inhibited by optochin (ethyl hydrocuprein hydrochloride)

Pathology: Fibrinopurulent serositis affecting meninges, pleura, peritoneum, and/or joints. Often severe fibrinopurulent pneumonia. Sometimes only septicemia, especially if splenectomized. Numerous thrombi and infarcts - can result in permanent CNS damage if survive. Diplococci easy to see on gram stained smear of exudates.

Fox. JG, et al. Bacterial meningoencephalitis in rhesus monkeys: clinical and pathological features. Lab Anim Sci 21:558-563, 1971.

Kaufmann AF, et al. Pneumococcal meningitis and peritonitis in rhesus monkeys. JAVMA 155:1158-1162, 1969.

Solleveld HA, et al. Clinicopathologic study of six cases of meningitis and meningoencephalitis in chimpanzees. Lab Anim Sci 34:86-90, 1984.

Klumpp SA, et al. Pneumococcal meningitis. In: Jones TC, et al. (eds). Monographs on pathology of laboratory animals: Nonhuman primates II. Springer-Verlag, 1993, 169-173.

Lair S, et al. Myeloencephalitis associated with a viridans group Streptococcus in a colony of Japanese macaques (Macaca fuscata). Vet Pathol 33:99-103, 1996.

Etiology: Yersinia pseudotuberculosis, Y. enterocolitica.

Transmission: Wild birds and rodents are reservoir hosts. Transmission by ingestion of feed contaminated by feces of infected vermin.

Clinical: Affected monkeys are often found dead but sometimes show diarrhea, depression, and dehydration. Yersinia is occasionally associated with abortions and stillbirths.

Pathology: The infection begins as a focal necrotizing enteritis and mesenteric lymphadenitis, which rapidly becomes septicemic resulting in necropurulent hepatitis, splenitis, and myelitis. Large colonies of gram negative bacteria in necrotic centers are nearly diagnostic.

Buhles WC, et al. Yersinia pseudotuberculosis infection: study of an epizootic in squirrel monkeys. J Clin Microbiol 13:519-525, 1981.

Bronson RT, et al. An outbreak of infection by Yersinia pseudotuberculosis in nonhuman primates. Am J Pathol 69:289-303, 1972.

MacArthur JA, et al. Yersiniosis in a breeding unit of Macaca fascicularis. Lab Anim 17:151-155, 1983.

Baggs RB, et al. Pseudotuberculosis (Yersinia enterocolitica) in the owl monkey. Lab Anim Sci 26:1079-1083, 1976.

Rosenberg DP, et al. Yersinia pseudotuberculosis infection in a group of Macaca fascicularis. JAVMA 177:818-821, 1980.

Bresnahan JF, et al. Yersinia enterocolitica infection in breeding colonies of ruffed lemurs. J Am Vet Med Assoc 185:1354-, 1984.

Chang J, et al. Fatal Yersinia pseudotuberculosis infection in captive bushbabies. J Am Vet Med Assoc 177:820-821, 1980.

Etiology: Listeria monocytogenes

Transmission: Listeria is widespread in the environment. Oral from contaminated food, transplacental

Clinical: Disease occurs in stillborn and neonatal infants. Abortion, intrauterine death, neonatal sepsis, meningoencephalitis in infants. Mother usually clinically normal.

Pathology: Purulent placentitis (hematogenous pattern), purulent meningoencephalitis, intrauterine pneumonia, focal necrosis in liver and other organs, gram-positive rods in tissues.

McClure HM, et al. Perinatal listeric septicemia in a Celebese black ape. JAVMA 167:637-638, 1975.

Tribe GW. Listeria monocytogenes associated with abortion in cynomolgus monkeys. Primate Supply 7:9-13, 1983.

Heldstab A, et al. Listeriosis in an adult female chimpanzee (Pan troglodytes). J Comp Pathol 92:609-612, 1982.

Chalifoux LV, et al. Septicemia and meningoencephalitis caused by Listeria monocytogenes in a neonatal Macaca fascicularis. J Med Primatol 10:336-339, 1981.

Anderson DC, et al. Listeriosis. In: Jones TC, et al. (eds). Monographs on Pathology of Laboratory Animals: Nonhuman Primates I, Springer-Verlag, 1993, 135-141.

Etiology: Bordetella bronchiseptica

Transmission: Respiratory

Clinical: Asymptomatic carriers. Mucopurulent nasal discharge, dyspnea, death.

Pathology: Fibrinopurulent hemorrhagic bronchopneumonia. Fibroplasia around bronchioles.

Graves IL. Bordetella bronchiseptica isolated from a fatal case of bronchopneumonia in an African green monkey. Lab Anim Care 18:405-406, 1968.

Kohn DF, et al. Bordetella bronchiseptica infection in the lesser bushbaby (Galago senegalensis). Lab Anim Sci 27:279-280, 1977.

Seibold HR, et al. Pneumonia associated with Bordetella bronchiseptica in Callicebus species primates. Lab Anim Care 20:456-461, 1970.

Etiology: Branhamella catarrhalis

Transmission: aerosol

Clinical: "Bloody nose syndrome" in cynomolgus macaques. Epistaxis, periorbital edema. Differentiate from viral hemorrhagic syndromes by isolation of organism and response to penicillin. May be associated with low humidity.

Pathology: Mucohemorrhagic rhinitis with gram-negative diplococci in exudate.

References:

VandeWoude SJ, et al. The role of Branhamella catarrhalis in the "bloody-nose syndrome" of cynomolgus macaques. Lab Anim Sci 41:401-406, 1991

Cooper JE, et al. An outbreak of epistaxis in cynomolgus monkeys (Macaca fascicularis). Vet Rec 99:438-439, 1976

Olson LC, et al. Epistaxis and bullae in cynomolgus macaques. Lab Anim Sci 33:377-379, 1983

Etiology: Clostridium tetani.

Transmission: C. tetani is a soil organism and an obligate anaerobe that contaminates wounds and causes postpartum infections. .

Clinical: Begins in upper limbs, then lower. Deliberate stiff gait, trismus, extensor rigidity, opisthotonos. Usually fatal in l-10 days due to respiratory paralysis and exhaustion. Tetanus is a non-immunizing disease - multiple episodes are possible. Antibody is not usually detectable in affected animals.

Pathology: None. Must be diagnosed clinically.

Rawlins RG, et al. A five-year study of tetanus in the Cayo Santiago rhesus monkey colony: behavioral description and epizootiology. Am J Primatol 3:23-39, 1982. Kessler MJ, et al. Clinical description of tetanus in squirrel monkeys. Lab Anim Sci 29:240-242, 1979.

Goodwin WJ, et al. Tetanus in baboons of a corral breeding colony. Lab Anim Sci 37:231-232, 1987.

Etiology: Staphylococcus aureus

Transmission: Staphylococcus is commonly carried asymptomatically in the nose and throat but occasionally infects breaks in the skin and invades the bloodstream.

Clinical: Pustular dermatitis in young animals. Breaks in skin become infected resulting in cellulitis, abscesses, and lymphadenitis. Bacteremia often develops, leading to visceral abscesses, endocarditis, and septic shock. Vegetative valvulitis may cause septic emboli and infarcts in various organs. Indwelling catheters are a common source of infection. The source of infection is usually clinically obvious.

Pathology: Cellulitis, abscesses filled with thick creamy pus, fibrinous pericarditis, vegetative valvulitis, thrombosis and infarction. Histologic lesions consist of fibrinopurulent exudate with masses of gram-positive cocci. Monkeys sometimes develop secondary immune complex glomerulonephritis.

Etiology: Klebsiella pneumoniae

Transmission: Respiratory. Carried in nose and throat.

Clinical: Nasal discharge, signs of pneumonia or meningitis.

Pathology: Fibrinopurulent pneumonia and serositis, septicemia. Abundant gram-negative bacteria with prominent capsules in exudate. Exudate sometimes has a gelatinous consistency.

Snyder SB, et al. A study of Klebsiella infections in owl monkeys. JAVMA 157:1935-1939, 1970.

Hunt DE, et al. Control of an acute Klebsiella pneumoniae infection in a rhesus monkey colony. Lab Anim Care 18:182-185, 1968.

Fox JG, et al. Meningitis caused by Klebsiella sp. in two rhesus monkeys. JAVMA 167:634-636, 1975.

Gozalo A, et al. Klebsiella pneumoniae infection in a new world nonhuman primate center. Lab Primate Newsletter 30:13-15, 1991.

Etiology: E. coli

Transmission: Fecal-oral

Clinical: Pneumonia, meningitis, diarrhea.

Pathology: Fibrinopurulent pneumonia and serositis, pyelonephritis, hemorrhagic gastroenteritis.

McClure HM, et al. Enteropathogenic Escherichia coli infection in anthropoid apes. JAVMA 161:687-689, 1972.

Etiology: Pseudomonas aeruginosa and P. pseudomallei (Melioidosis)

Transmission: P. aeruginosa ubiquitous in moist environments worldwide. P. pseudomallei is an environmental saprophyte in SE Asia.

Clinical: P. aeruginosa is predominantly a problem in debilitated, burned, immunocompromised, and neutropenic patients. Common in animals immunosuppressed with steroids or whole body irradiation. P. pseudomallei may infect animals and man in SE Asia and can remain clinically latent for years.

Pathology: P. aeruginosa can infect many tissues, but the pathological hallmark is a vasculitis without thrombosis. Bacilli are seen in the vessel wall. There is severe necrosis usually, but neutrophils are often sparse. P. pseudomallei causes melioidosis, which may include pneumonia, abscesses, and granulomas.

References:

Fritz PE, et al. Naturally occurring melioidosis in a colonized rhesus monkey. Lab Anim 20:281-285, 1986.

Mutalib AR, et al. Melioidosis in a banded leaf-monkey (Presbytis melalophos). Vet Rec 115:438-439, 1984.

Bodey GP, et al. Infections caused by Pseudomonas aeruginosa. Rev Inf Dis 5:279-313, 1983.

Etiology: Nocardia asteroides

Transmission: Organism common in soil & organic material. Inhalation, ingestion.

Clinical: Often associated with defects in cellular immunity.

Pathology: Infections often predominantly in the lungs, but may disseminate. Mixed inflammatory infiltrates, abscesses, granulomas. The organism is gram-positive, filamentous, branching, often beaded, and variably acid-fast.

Liebenberg SP, et al. Disseminated nocardiosis in three macaque monkeys. Lab Anim Sci 35:162-166, 1985.

Sakakibara I, et al. Spontaneous nocardiosis with brain abscess caused by Nocardia asteroides in a cynomolgus monkey. J Med Primatol 13:89-95, 1984.

Etiology: Herpesvirus simiae (B Virus), Cercopithecine herpesvirus I

Transmission: Bites, scratches, venereal. Virus shed in oral and genital secretions, vesicular fluid. Viremia is rare, but does occur. No vertical transmission. Virus latent in sensory ganglia. Humans have become infected from monkey cell cultures. About half of human infections have been in animal handlers and about half in laboratory workers.

Clinical: The rate of seropositivity in conventional captive adult macaques is 73-100%. Herpes B causes a lifeling infection with intermittent reactivation and virus shedding in saliva or genital secretions. In macaques, lesions consist of vesicles and ulcers in the oral cavity and lips and conjunctivitis. Disseminated infections occur rarely, esp. in young and debilitated animals. Latent infection is common. Epizootic disease has been reported in M. radiata. Asymptomatic macaques can shed virus!! There have been about 50 human cases reported, of which 29 were fatal. In humans, vesicles at site of inoculation, conjunctivitis, flu-like symptoms, severe often fatal encephalomyelitis. There is no evidence of asymptomatic human infections. Antibody titers to Herpes simplex virus are not protective in humans.

Pathology: In monkeys, vesicles or ulcers on oral mucous membranes and esophagus, focal necrosis in various organs if generalized. In humans, conjunctivitis, vesicles at site of bite or scratch, and necrosis of CNS. Intranuclear inclusion bodies and syncytial cells associated with lesions.

Virus Detection: Most infected animals are seropositive, but a small percentage are seronegative. Culture and PCR can be used to detect virus, but are only useful if the animal is actively shedding virus. Virus is usually shed only intermittently and briefly. PCR of cranial and dorsal root ganglia provides the best evidence of viral status, but is not possible in living animals.

Colony Management: One should assume that all macaques are shedding B virus. Never handle monkeys without proper protection (masks and gloves at very least), properly trained personnel, and adequate equipment. Avoid handling unanesthetized monkeys whenever possible.

Management programs must be tailored to individual circumstances. One should consider serological screening of all macaques. If circumstances allow, seropositive and seronegative animals could be separated into clean and infected colonies. Colonies in the USA vary between 10-90% seropositive. The percentage of seropositive monkeys which are shedding virus at any one time is unknown, but is probably very small. Some monkeys shed virus consistently and others intermittently. One could consider viral culture on seropositive monkeys, depending on the degree of human contact. Virus shedders which come into contact with humans should be eliminated, if possible. Even in SPF colonies, the risk is not zero, because rare seronegative monkeys are actually infected.

Herpes B can infect and cause fatal disease in owl monkeys, marmosets, African green monkeys, gibbons, and patas monkeys. Do not mix species!

Management of Bites: Wounds should be cleaned immediately. Wound excision should be considered if surgical expertise is immediately available. Draw blood from the monkey and the human victim immediately for serological testing. Culture the monkey (buccal and conjunctival swabs) immediately. Do follow-up cultures and consider placing the victim on acyclovir if the monkey was shedding virus at the time of the bite. Acyclovir appears to be helpful if given before neurological damage occurs. Physicians should consult Dr. Louisa Chapman, Centers for Disease Control, (404-639-3747).

Serology & Viral Culture: Samples for serology or viral culture should be sent to the NIH B Virus Resource Laboratory, Viral Immunology Center, Georgia State University, 50 Decatur Street, Atlanta, GA 30303. Information and submission forms can be obtained from Dr. Richard D. Henkel, NIH B Virus Reference Laboratory, Georgia State University, PO Box 4118, Atlanta, GA 30302-4118. (404-651-0808; biordh@panther.gsu.edu)

Keeble SA, et al. Natural virus-B infection in rhesus monkeys. J Path Bacteriol 76:189-199.

Boulter EA, et al. A comparison of neutralization tests for the detection of antibodies to Herpesvirus simiae (Monkey B Virus). Lab Anim Sci 32:150-152, 1982.

Palmer AE. B virus, Herpesvirus simiae: Historical perspective. J Med Primatol 16:99-130, 1987.

CDC. B-virus infection in humans - Pensacola, Florida. MMWR 36:289-290, 295-296, 1987.

CDC. Guidelines for prevention of Herpesvirus simiae (B virus) infection in monkey handlers. MMWR. 36:679-682, 687-689, 1987 or J Med Primatol 17:77-83, 1988.

CDC. Update: Ebola-related filovirus infection in nonhuman primates and interim guidelines for handling nonhuman primates during transit and quarantine. MMWR 39:22-30, 1990.

Wansbrough-Jones MH, et al. Prophylaxis against B virus infection. Br Med J 297:909, 1988.

Holmes GP, et al. B virus (Herpesvirus simiae) infection in humans: epidemiologic investigation of a cluster. Ann Int Med 112:833-839, 1990.

Lees DN, et al. Herpesvirus simiae (B virus) antibody response and virus shedding in experimental primary infection of cynomolgus monkeys. Lab Anim Sci 41:360-363, 1991.

Weigler BJ. Biology of B-virus in macaque and human hosts-a review. Clin Inf Dis 14:2, 1992.

Chellman GJ, et al. Activation of B virus (Herpesvirus simiae) in chronically immunosuppressed cynomolgus monkeys. Lab Anim Sci 42:146-151, 1992

Sauber JJ, et al. An attempt to eradicate Herpesvirus simiae from a rhesus monkey breeding colony. Lab Anim Sci 42:458-462, 1992.

Wells DL, et al. Herpesvirus simiae contamination of primary rhesus monkey kidney cell cultures. Diagn Microbiol Infect Dis 12:333-336, 1989.

Weir EC, et al. Infrequent shedding and transmission of Herpesvirus simiae from seropositive macaques. Lab Anim Sci 43:541-544, 1993.

Simon MA, et al. Disseminated B virus infection in a cynomolgus monkey. Lab Anim Sci 43:545-550, 1993.

Hunt RD, et al. Herpesvirus B infection. In: Jones TC, et al. (eds). Monographs on pathology of laboratory animals: Nonhuman primates I. Springer-Verlag, 1993, 78-81.

Slomka MJ, et al. Polymerase chain reaction for detection of herpesvirus simiae (B virus) in clinical specimens. Arch Virol 131:89-99, 1993.

Anderson DC, et al. Primary Herpesvirus simiae (B-virus) infection in infant macaques. Lab Anim Sci 44:526-530, 1994.

Ward JA, et al. B virus-specific pathogen-free (SPF) breeding colonies of macaques: Issues, surveillance, and results in 1992. Lab Anim Sci 44:222-228, 1994.

Holmes GP, et al. Guidelines for the prevention and treatment of B-virus infections in exposed persons. Clin Infect Dis 20:421-439, 1995.

Davenport DS, et al. Diagnosis and management of human B virus (Herpesvirus simiae) infections in Michigan. Clin Inf Dis 19:33-41, 1994.

Carlson CS, et al. Fatal disseminated Cercopithecine Herpesvirus 1 (Herpes B) infection in Cynomolgus monkeys (Macaca fascicularis). Vet Pathol 34:405-414, 1997.

Ostrowski SR, et al. B-virus from pet macaque monkeys: An emerging threat in the United States? Emerg Inf Dis 4: , 1998

Etiology: Alphaherpesvirus related to H. simiae, Herpesvirus papio 2, HSV-1, HSV-2.

Transmission: SA8 is endemic in African green monkeys. No human infections reported.

Pathology: Lesions rarely reported in cercopithecoids. Lesions in baboons previously attributed to SA8 were probably due to Herpesvirus papio 2.

Malherbe H, et al. Neurotropic virus in African monkeys. Lancet ii:530, 1958.

Etiology: Alpha herpesvirus related to H. simiae and SA8. Previously identified as SA8.

Transmission: Endemic in baboons. Venereal and oral transmission.

Pathology: Oral, genital, and cutaneous vesicular, papillomatous or ulcerative lesions in baboons. Inguinal lymphadenopathy. Lesions usually resolve spontaneously, but may recur. May be a good model for H. simplex 2 in humans.

Levin JL, et al. A naturally occurring epizootic of simian agent 8 in the baboon. Lab Anim Sci 38:394-397, 1988.

Martino MA, et al. Clinical disease associated with simian agent 8 infection in the baboon. Lab Anim Sci 48:18-22, 1998.

Eberle R, et al. Shedding and transmission of baboon Herpesvirus papio 2 (HVP2) in a breeding colony. Lab Anim Sci 48:23-28, 1998.

Etiology: Group of closely-related herpesviruses including Delta herpesvirus, Medical Lake macaque virus, Liverpool vervet monkey virus, and others. All are antigenically related to human varicella-zoster.

Transmission: Respiratory. Latency is common and the origin of some outbreaks is unexplained.

Clinical: Affects patas, African green monkeys, macaques. Herpetic rash, depression, respiratory difficulty.

Pathology: Vesicles on skin, oral mucous membranes, and esophagus; focal necrosis in lung, liver, spleen, lymph nodes, adrenal, bone marrow, intestinal tract. Intranuclear inclusion bodies. Becomes latent in ganglia.

Bladely GA, et al. A varicella-like disease in macaque monkeys. J Infect Dis 127:617-625, 1973.

Iltis JP, et al. Simian varicella virus (Delta Herpesvirus) infection of Patas monkeys leading to pneumonia and encephalitis. Soc Exp Biol Med 169:266-279, 1982.

Schmidt NJ, et al. Serological investigation of an outbreak of simian varicella in Erythrocebus patas monkeys. J Clin Microbiol 18:901-904, 1983.

Roberts ED, et al. Pathologic changes of experimental simian varicella (Delta herpesvirus) infection in African green monkeys. Am J Vet Res 45:523-530, 1984.

White RJ, et al. Chickenpox in young anthropoid apes. Clinical and laboratory findings. J Am Vet Med Assoc 161:690-692, 1972.

Mahalingam R, et al. Prevalence and distribution of latent simian varicella virus DNA in monkey ganglia. Virol 188:193-197, 1992.

Roberts ED. Simian varicella. In: Jones TC, et al. (eds). Monographs on pathology of laboratory animals: Nonhuman primates I. Springer-Verlag, 1993, 93-100.

Gray WL, et al. Rapid diagnosis of simian varicella using the polymerase chain reaction. Lab Anim Sci 48:45-49, 1998.

Gray WL, et al. Experimental simian varicella virus infection of St. Kitts vervet monkeys. J Med Primatol 27:177-183, 1998.

Etiology: Gammaherpesvirus (Cebid herpesvirus 2)

Transmission: oral

Clinical: Squirrel monkey is natural host with a high incidence of natural infection. No disease in squirrel monkeys. Produces lymphomas in marmosets, owl monkeys, African green monkeys, howler monkeys, spider monkeys. Lymphadenopathy, hepatomegaly, splenomegaly, leukemia.

Pathology: None in squirrel monkeys - lifelong latent infection of T-cells. In tumorigenic host, leukemic infiltrates of immature lymphocytes in liver, kidney, spleen, lymph nodes, adrenal and other organs. Focal necrosis in liver, spleen, kidney, adrenal cortex, lymph nodes, thymus, bone marrow. No inclusion bodies.

Hunt RD, et al. Morphology of a disease with features of malignant lymphoma in marmosets and owl monkeys inoculated with Herpesvirus saimiri. J Natl Cancer Inst 44:447-465, 1970.

Melendez LV, et al. Herpes saimiri II. Experimentally induced malignant lymphoma in primates. Lab Anim Care 19:378-386, 1969.

Falk LA, et al. Oral excretion of Herpesvirus saimiri in captive squirrel monkeys and incidence of infection in feral squirrel monkeys. J Natl Cancer Inst 51:1987-1989, 1973.

Hunt RD, et al. Herpesvirus saimiri and Herpesvirus ateles infection. In: Jones TC, et al. (eds). Monographs on pathology of laboratory animals: Nonhuman primates I. Springer-Verlag, 1993, 87-93.

Etiology: Alphaherpesvirus (Cebid herpesvirus 1)

Clinical: Squirrel monkey is natural host with a high incidence of natural infection. Infections usually inapparent, but may have oral vesicles or ulcers, simialr to H. simplex in man and H simiae in macaques. Herpes T produces a fatal generalized disease in owl monkeys and marmosets characterized by a vesicular rash and oral vesicles and ulcers.

Pathology: None or oral vesicles in squirrel monkey. In owl monkeys, tamarins, and marmosets, typical generalized herpes with vesicles and ulcers on skin and oral mucous membranes, ulcers in GI tract, focal necrosis in liver, adrenal, spleen, lung, lymph nodes. Occasional syncytial cells. Eosinophilic intranuclear inclusion bodies. In colonies there is often high morbidity and mortality.

Melnick JL, et al. A new member of the herpes virus group isolated from South American marmosets. J Immun 92:596-601, 1964.

Holmes AW, et al. Isolation and characterization of a new herpes virus. J Immun 92:602-610, 1964.

Hunt RD, et al. A pathologic study of herpes-T in the owl monkey (Aotus trivirgatus). Path Vet 3:1-26, 1966.

Daniel MD, et al. Isolation of herpes-T virus from a spontaneous disease in squirrel monkeys (Saimiri sciureus). Archiv Gesamte Virusforschung 22:324-331, 1967.

Hunt RD, et al. Herpesvirus platyrrhinae infection. In: Jones TC, et al. (eds). Monographs on pathology of laboratory animals: Nonhuman primates I. Springer-Verlag, 1993, 100-103.

Etiology: Herpesvirus

Clinical: Natural host is spider monkey (Ateles geofroyii). No disease in spider monkey. Produces lymphomas in marmosets and owl monkeys. Lymphadenopathy, hepatomegaly, splenomegaly.

Pathology: Malignant lymphoma in lymph nodes, liver spleen, kidney, adrenal, bone marrow and other tissues.

Hunt RD, et al. Pathologic features of Herpesvirus ateles lymphoma in cotton-topped marmoset (Saguinus oedipus). J Natl Cancer Inst 49:1631, 1972.

Rangan SRS, et al. Tumors and viruses in nonhuman primates. Adv Virus Res 24:1, 1979.

Hunt RD, et al. Herpesvirus saimiri and Herpesvirus ateles infection. In: Jones TC, et al. (eds). Monographs on pathology of laboratory animals: Nonhuman primates I. Springer-Verlag, 1993, 87-93.

Etiology: gammaherpesvirus closely related to Human herpesvirus-8 (KSHV). Also called RFHVMn & RFHVMm.

Clinical: High incidence of seropositivity in some research colonies of Macaca mulatta & M. nemestrina. Possible association with retroperitoneal fibromatosis.

Rose TM, et al. Identification of two homologs of the Kaposi’s sarcoma-associated herpesvirus (human herpesvirus 8) in retroperitoneal fibromatosis of different macaque species. J Virol 71:4138-4144, 1997.

Desrosiers RC, et al. A herpesvirus of rhesus monkeys related to the human Kaposi’s sarcoma-associated herpesvirus. J Virol 71:9764-9769, 1997.

Etiology: Herpes simplex virus

Transmission: Latent or active infection in many humans, which are the natural reservoir. Human to monkey and monkey to monkey transmission from active lesions.

Clinical: Lesions may be local or generalized. Oral vesicles and ulcers, conjunctivitis, encephalitis, death. Owl monkey, tree shrew, lemur, marmosets, tamarins susceptible to generalized disease. Chimpanzees and gibbons can be infected, but usually remains confined to skin, oral cavity, external genitalia, and conjunctiva.

Pathology: Oral, lingual, labial, or genital vesicles & ulcers. Conjunctivitis, keratitis. Necrotizing meningoencephalitis, focal necrosis in visceral organs. Multinucleated cells and intranuclear inclusion bodies.

Smith PC, et al. The gibbon (Hylobates lar); A new primate host for Herpesvirus hominus. I. A new natural epizootic in a laboratory colony. J Infect Dis 120:292-297, 1969.

Melendez LV, et al. Natural herpes simplex infection in the owl monkey (Aotus trivirgatus). Lab Anim Care 19:38-45, 1969.

McClure HM, et al. Viral diseases noted in the Yerkes Primate Center Colony. Lab Anim Sci 21:1002-1010, 1971.

McClure HM, et al. Natural genital Herpesvirus hominis infection in chimpanzees (Pan troglodytes and Pan paniscus). Lab Anim Sci 30:895-901, 1980.

Heldstab A, et al. Spontaneous generalized Herpesvirus hominis infection of a lowland gorilla (Gorilla gorilla gorilla). J Med Primatol 10:129-135, 1981.

Hunt RD. Herpesvirus simplex infection. In: Jones TC, et al. (eds). Monographs on pathology of laboratory animals: Nonhuman primates I. Springer-Verlag, 1993, 82-86.

Etiology: Betaherpesvirus

Transmission: Horizontal (shed in urine), transplacental, highly species-specific.

Clinical: Usually none. Widespread latent infections in macaques, with most seroconverting during the first year of life. Disease produced only in fetuses and immunodeficient individuals. CNS and respiratory tract signs. CMV is a common opportunistic infection in SIV and SRV infected macaques.

Pathology: In immunodeficient animals, generalized infections with necrotizing meningitis and neuritis, interstitial pneumonia, arteritis, enterocolitis, orchitis, and focal necrosis in liver and spleen. Characteristic large basophilic intranuclear inclusion bodies and granular eosinophilic cytoplasmic inclusion bodies in mesenchymal cells (not surface epithelium like other herpesviruses).

Baskin GB. Disseminated cytomegalovirus infection in immunodeficient rhesus monkeys. Am J Pathol 129:345-352, 1987.

Swack NS, et al. Natural and experimental simian cytomegalovirus infections at a primate center. J Med Primatol 11:169-177, 1982.

Asher DM, et al. Persistent shedding of cytomegalovirus in the urine of healthy rhesus monkeys. Proc Soc Exp Biol Med 145:794-801, 1974.

Baskin GB. Cytomegalovirus infection in nonhuman primates. In: Jones TC, et al. (eds) Monographs on Pathology of Laboratory Animals: Nonhuman Primates I, Springer-Verlag, 1993, 32-37.

Vogel P, et al. Seroepidemiologic studies of cytomegalovirus infection in a breeding population of rhesus macaques. Lab Anim Sci 44:25-30, 1994.

Kuhn E-M, et al. Immunohistochemical studies of productive rhesus cytomegalovirus infection in rhesus monkeys (Macaca mulatta) infected with Siimian Immunodeficiency Virus. Vet Pathol 36:51-56, 1999.

Etiology: Nonhuman primate EBV-related Herpesviruses

Transmission: Contact.

Clinical: Most infections are latent. In immunodeficient animals, EBV has been associated with lymphoma and with squamous epithelial proliferative lesions.

Pathology: Extranodal B-cell lymphoma or squamous cell proliferations resembling oral hairy leukoplakia on oral, genital, and cutaneous surfaces in immunodeficient animals. Intranuclear inclusions are present in epithelial lesions.

Rangan SRS, et al. Epstein-Barr virus-related herpesvirus from a rhesus monkey (Macaca mulatta) with malignant lymphoma. Int J Cancer 38:425-432, 1986.

Landon JC, et al. Seroepidemiologic studies of Epstein-Barr virus antibody in monkeys. J Natl Cancer Inst 46:881-884, 1971.

Ishida T, et al. Survey of nonhuman primates for antibodies reactive with Epstein-Barr virus antigens and susceptibility of their lymphocytes for immortalization with EBV. J Med Primatol 16:359-371, 1987.

Bocker JF, et al. Characterization of an EBV-like virus from African Green Monkey lymphoblasts. Virol 101:291-295, 1980.

Fujimoto K, et al. Presence of antibody to Cyno-EBV in domestically bred cynomolgus monkeys (Macaca fascicularis). J Med Primatol 20:42-45, 1991.

Ishida T, et al. Serological features of infection with an Epstein-Barr-virus-like agent in Japanese macaques (Macaca fuscata). Folia Primatol 61:228-233, 1993.

Baskin GB, et al. Squamous epithelial proliferative lesions associated with rhEBV in SIV-infected rhesus monkeys. J Inf Dis 172:535-539, 1995.

Etiology: Encephalomyocarditis virus (picornavirus)

Transmission: Oral, other? Probable rodent reservoir.

Clinical: Sudden death. Causes myocarditis in nonhuman primates, pigs, elephants, some others. EMCV is probably not a significant human pathogen, although some people are seropositive.

Pathology: Pericardial effusion, pale areas in myocardium. Myofiber necrosis with inflammation and edema. Secondary lesions of acute heart failure. Extensive myocardial scarring in animals that survive acute infection. Some strains of EMCV cause necrosis of the exocrine pancreas in some species.

Helwig FC, et al. A filter-passing agent producing interstitial myocarditis in anthropoid apes and small animals. Science 102:31-33, 1945.

Roca-Garcia M, et al. The isolation of encephalomyocarditis virus from Aotus monkeys. Am J Trop Med 6:840-852, 1957.

Blanchard JL, et al. Encephalomyocarditis virus infection in African green and squirrel monkeys: Comparison of pathologic effects. Lab Anim Sci 37:635-639, 1987.

Wells SK, et al. Encephalomyocarditis virus: Epizootic in a zoological collection. J Zoo Wildlife Med 20:291-296, 1989.

Hubbard GB, et al. An encephalomyocarditis virus epizootic in a baboon colony. Lab Anim Sci 42:233-239, 1992.

Baskin GB. Encephalomyocarditis virus infection, nonhuman primates. In: Jones TC, et al. (eds). Monographs on pathology of laboratory animals: Nonhuman primates I. Springer-Verlag, 1993, 104-107.

Emerson CL, et al. Antibody responses to two encephalomyocarditis virus vaccines in rhesus macaques (Macaca mulatta). J Med Primatol 25:42-45, 1996.

Etiology: Orthopoxvirus immunologically related to smallpox and vaccinia

Transmission: Zoonotic disease of monkeys and humans in tropical rain forests of western and central Africa. Old and New World monkeys and apes also susceptible. Animal reservoir unknown, but possibly squirrels and probably not monkeys. Occurs sporadically, not epidemically.

Clinical: Vaccinia is protective, but hasn’t been used since 1980. Disease in children resembles discrete ordinary smallpox, except lymphadenopathy occurs commonly in monkeypox. Human to human transmission has occurred. In monkeys, disease may be mild to fatal. Usually see 1 to 4 mm in diameter cutaneous papules that become pustules and then crust over and drop off, leaving small scars. In more severe disease, see facial edema, dyspnea, oral ulcers, and lymphadenopathy.

Pathology: Hyperplasia and necrosis of epidermis, with swelling of keratinocytes and large eosinophilic intracytoplasmic inclusions. Visceral lesions can occur.

Von Magnus P, et al. A pox-like disease in cynomolgus monkeys. Acta Pathol Microbiol Scand 46:156-176, 1959.

Prier JE, et al. A pox disease of monkeys. Ann NY Acad Sci

Gispen R, et al. Histopathological and virological studies on monkeypox. Arch Ges Virusforsch 21:205-216, 1967.

Wenner HA, et al. Studies on pathogenesis of monkeypox. III. Histopathological lesions and sites of immunofluorescence. Arch Ges Virusforsch 27:179-197, 1969.

Sauer RM, et al. Studies on a pox disease of monkeys. I. Pathology. Am J Vet Res 21:377-380, 1960.

Peters JC. An outbreak of monkeypox in the zoo at Rotterdam. In: Balner H, et al (eds). Infections and immunosuppression in subhuman primates. Williams & Wilkins, 1970.

Arita I, et al. Human monkeypox: A newly emerged orthopoxvirus zoonosis in the tropical rain forests of Africa. Am J Trop Med Hyg 34:781-789, 1985.

Khodakevich L, et al. The role of squirrels in sustaining monkeypox virus transmission. Trop Geogr Med 39:115-122, 1987.

Gough AW, et al. Poxvirus infection in a colony of common marmosets (Callithrix jacchus). Lab Anim Sci 32:87-90, 1982.

Centers for Disease Control. Human Monkeypox - Kasai Oriental, Zaire, 1996-1997. MMWR 46:304-307, 1997.

Etiology: poxvirus

Transmission: Mosquitoe vector.

Clinical: Natural infections have occurred in rhesus and baboons. Humans are also susceptible. Rapidly growing subcutaneous nodules up to 4 cm diameter on head and limbs. These spontaneously slough and heal in 6 to 12 weeks.

Pathology: Unlike other poxviruses, Yaba pox infects histiocytes rather than epithelial cells. Yaba pox virus induces subcutaneous proliferation of round to polygonal histiocytes which often contain eosinophilic cytoplasmic inclusions. Usually described as benign histiocytomas. Similar to lumpy skin disease of cattle.

Bearcroft WGC, et al. An outbreak of subcutaneous tumors in rhesus monkeys. Nature 182:195-96, 1958.

Niven JSF, et al. Subcutaneous "growths" in monkeys produced by a poxvirus. J Pathol Bacteriol 81:1-14, 1961.

Grace JT Jr, et al. Human susceptibility to a simian tumor virus. Ann NY Acad Sci 108:1123-1128. 1963.

Ambrus JL, et al. "Spontaneous" occurrence of Yaba tumor in a monkey colony. Experientia 25:64-65, 1969.

Schmidt LH. Yaba and Yaba-like viruses. In: Balner H, et al (eds). Infections and immunosuppression in subhuman primates. Williams & Wilkins, 1970.

Bruestle ME, et al. Naturally occurring Yaba tumor in a baboon (Papio papio). Lab Anim Sci 31:292-294, 1981.

Whittaker D, et al. A Yaba-like condition in a young baboon (Papio anubis). Lab Animals 19:177-179, 1985.

Etiology: Tana poxvirus (unrelated to smallpox)

Clinical: Infects macaques and humans. Multiple crusted macules on face and arms. Heal in 3 to 4 weeks.

Pathology: Epidermal hyperplasia and necrosis. Epithelial cells swollen and contain eosinophilic cytoplasmic inclusion bodies.

References:

Hall AS, et al. A contagious pox disease in monkeys. J Am Vet Med Assn 151:833-838, 1967.

McNulty WP, et al. A pox disease in monkeys transmitted to man. Arch Dermatol 97:286-293, 1968.

Downie AW, et al. Tanapox: A new disease caused by a pox virus. Brit Med J 1:363-368, 1971.

Etiology: poxvirus unrelated to smallpox

Clinical: Humans, chimpanzees. Smooth-surfaced, hemispheric, waxy, umbilicated epithelial papules, 3-8 mm diameter, anywhere on skin, but especially eyelid and groin.

Pathology: Marked acanthosis with large basophilic intracytoplasmic inclusion bodies that become more prominent towards the skin surface.

Douglas JD, et al. Molluscum contagiosum in chimpanzees. J Am Vet Med Assn 151:901-904, 1967.

Etiology: Human measles virus (Paramyxoviridae:Morbillivirus)

Transmission: Respiratory. Human reservoir. Measles is not a natural disease of macaques, but is acquired through contact with humans.

Clinical: Affects apes, macaques, baboons, African green monkeys, marmosets, and squirrel monkeys. May be subclinical or cause maculopapular rash, conjunctivitis, facial erythema, respiratory difficulty, diarrhea (especially in marmosets and owl monkeys). Causes temporary immunosuppression which may affect research results.

Pathology: Focal necrosis on oral mucous membranes, interstitial pneumonia, syncytial cells in skin, lymph nodes, lung. Intranuclear and intracytoplasmic inclusion bodies. In marmosets and owl monkeys measles is an often fatal gastroenterocolitis rather than a predominantly respiratory infection. Measles virus is immunosuppressive.

References:

Hall WC, et al. Pathology of measles in rhesus monkeys. Vet Pathol 8:307-319, 1971.

Klutch MJ, et al. Fatal measles infection in marmosets. Proc Am Soc Microbiol p. 308, 1979.

Steele MD, et al. Spontaneous paramyxoviral encephalitis in nonhuman primates (Macaca mulatta and M. nemestrina). Vet Pathol 19:132-139, 1982.

Lorenz D, et al. Susceptibility of tamarins (Saguinus) to measles virus. Lab Anim Sci 30:661-665, 1980.

Welshman MD. Measles in the cynomolgus monkey (Macaca fascicularis). Vet Rec 124:184-186, 1989.

Lowenstine LJ. Measles virus infection, nonhuman primates. In: Jones TC, et al. (eds). Monographs on pathology of laboratory animals: Nonhuman primates I. Springer-Verlag, 1993, 108-118.

Hunt RD, et al. Gastroenteritis due to paramyxovirus. In: Jones TC, et al. (eds). Monographs on pathology of laboratory animals: Nonhuman primates II. Springer-Verlag, 1993, 32-37.

Contreras G, et al. Possible influence of measles virus infection of cynomolgus monkeys on the outcome of the neurovirulence test for oral poliovirus vaccine. Biologicals 20:27-33, 1992.

van Binnendijk RS, et al. Monkeys in measles research. Current Topics in Microbiol Immunol 191:135-147, 1995.

Etiology: Lymphocytic choriomeningitis virus (Callitrichid hepatitis virus). Arenavirus.

Transmission: Rodent reservoir. Endemic in mice worldwide. May be spread by feeding pinkies or contact with mouse urine or oral secretions.

Clinical: Affects several species of tamarins and marmosets (Callitrichidae). May be found dead or die after showing weakness and anorexia for several days. May develop siezures and respiratory distress.

Pathology: Jaundice, subcutaneous and intramuscular hemorrhage, hepatosplenomegaly, pleuropericardial effusions. Microscopic changes in liver consist of hepatocellular swelling and necrosis, lymphocyte and neutrophil infiltrates, acidophilic bodies, and portal phlebitis. Other possible lesions include meningitis, encephalitis, gliosis, necrosis in spleen and lymph nodes and interstitial pneumonia. No inclusion bodies are present. Enveloped virus-like particles 85-105nm in diameter can be demonstrated in the RER and Golgi of degenerated hepatocytes by electron microscopy.

References:

Montali RJ, et al. A new transmissible viral hepatitis of marmosets and tamarins. J Inf Dis 160:759-765, 1989.

Ramsay EC, et al. Callitrichid hepatitis: Epizootiology of a fatal hepatitis in zoo tamarins and marmosets. J Zoo Wildlife Med 20:178-183, 1989.

Lucke VM, et al. An outbreak of hepatitis in marmosets in a zoological collection. Lab Anim 16:73-77, 1982.

Phillips LG. Suspected viral hepatitis in golden lion tamarins-case report. Ann Proc Am Assoc Zoo Vet pp34-35, 1981.

Montali RJ, et al. A common-source outbreak of callitrichid hepatitis in captive tamarins and marmosets. J Inf Dis 167:946-950, 1993.

Montali RJ. Callitrichid hepatitis. In: Jones TC, et al. (eds). Monographs on pathology of laboratory animals: Nonhuman primates II. Springer-Verlag, 1993, 61-62.

Scanga CA, et al. Serologic evidence of infection with lymphocytic choriomeningitis virus, the agent of callitrichid hepatitis, in primates in zoos, primate research centers, and a natural reserve. J Zoo Wildlife Med 24:469-474, 1993.

Montali RH, et al. Pathology and immunohistochemistry of callitrichid hepatitis, an emerging disease of captive new world primates caused by lymphocytic choriomeningitis virus. Am J Pathol 147:1441-1449, 1995

Etiology: Adenovirus (numerous)

Clinical: Usually none-frequently isolated from intestine and lung of healthy animals. Conjunctivitis and respiratory infections, diarrhea, pancreatitis (rhesus). Severe infections in immunodeficient animals.

Pathology: Necrotizing alveolitis and bronchiolitis, pneumonia, necrotizing pancreatitis, enteritis. Intranuclear inclusions vary from small and eosinophilic to large, basophilic, and "smudgy".

Boyce JT, et al. Simian adenoviral pneumonia. Am J Pathol 91:259-276, 1978.

Chandler FW, et al. Pancreatitis associated with an adenovirus in a rhesus monkey. Vet Pathol 11:165-171, 1974.

Baskin GB, et al. Adenovirus enteritis in SIV-infected rhesus monkeys. J Inf Dis 160:905-907, 1989.

Umemura T, et al. Aspiration pneumonia with adenovirus infection in a Japanese macaque (Macaca fuscata fuscata). Lab Anim 19:39-41, 1985.

Landon JC, et al. Viral induced simian conjunctivitis. Nature 222:683-684, 1969.

Martin BJ, et al. Pancreatitis associated with simian adenovirus 23 in a rhesus monkey. Lab Anim Sci 41:382-384, 1991.

Etiology: Papillomavirus

Clinical: Papillomas on skin, oral or genital mucosa.

Pathology: Focal hyperkeratosis, parakeratosis, acanthosis. Papillomavirus antigens can be demonstrated by immunohistochemistry and virions by TEM.

Sundberg JP, et al. Papillomavirus infections. In: Jones TC, et al. (eds). Nonhuman Primates II, Monographs on Pathology of Laboratory Animals, ILSI, Springer-Verlag, New York, 1993, 1-8.

Etiology: Papovavirus

Clinical: Circumscribed soft elevations of the oral mucosa of lips, tongue, gingiva. This is usually a benign condition that may persist for years or may spontaneously regress.

Pathology: Focal acanthosis with koilocytosis, mild chronic inflammation. Virions can be demonstrated by TEM in about 50% of cases.

Anderson DC, et al. Focal epithelial hyperplasia, Chimpanzees. In: Jones TC, et al. (eds). Nonhuman Primates II, Monographs on Pathology of Laboratory Animals, ILSI, Springer-Verlag, New York, 1993, 233-237

Hollander CF, et al. Focal epithelial hyperplasia: a virus-induced oral mucosal lesion in the chimpanzee. Oral Surg 33:220-226, 1972.

Tate CL, et al. Focal epithelial hyperplasia in the oral mucosa of a chimpanzee. J Am Vet Med Assn 163:619-621, 1973.

Glad WR, et al. Focal epithelial hyperplasia of the oral mucosa in two chimpanzees (Pan troglodytes). Am J Primatol 10:83-89, 1986.

Etiology: Papovavirus (Polyomavirus subgroup)

Transmission: Respiratory. Virus is shed in urine.

Clinical: Usually none. Widespread latent infection in wild and captive macaques. In immunodeficient animals can cause CNS and respiratory signs.

Pathology: Usually none. In immunocompromised animals, interstitial pneumonia, renal tubular necrosis, encephalitis, demyelination (progressive multifocal leukoencephalopathy). Lesions in brain may have typical distribution of PML or may be around ventricles (particularly in brainstem) and in superficial cortex. Large basophilic intranuclear inclusions in lung, oligodendroglia, renal tubular epithelium.

Gribble DH, et al. Spontaneous progressive multifocal leukoencephalopathy (PML) in macaques. Nature 254:602-604, 1975.

Holmberg CA, et al. Isolation of simian virus 40 from rhesus monkeys (Macaca mulatta) with spontaneous progressive multifocal leukoencephalopathy. J Inf Dis 136:593-596, 1977.

King NW, et al. Histopathologic changes in macaques with an acquired immunodeficiency syndrome (AIDS). Am J Pathol 113:382-388, 1983.

Sheffield WD, et al. Simian virus 40-associated fatal interstitial pneumonia and renal tubular necrosis in a rhesus monkey. J Inf Dis 142:618-622, 1980.

King NW. Simain virus 40 infection. In: Jones TC, et al. (eds) Monographs on Pathology of Laboratory Animals: Nonhuman Primates I, Springer-Verlag, 1993, 37-42.

Etiology: Arterivirus

Transmission: Simian Hemorrhagic Fever Virus is endemic in some wild Patas monkeys (Erythrocebus patas) and possibly other African species (African green monkeys, baboons), which remain persistently viremic, but asymptomatic for life. Animals may be viremic without antibody. Transmission from Patas to macaques appears to require parenteral exposure to blood or body fluids. The virus spreads much more readily among macaques by contact or aerosol.

Clinical: The virus causes explosive epidemics with nearly 100% mortality in macaques. Clinical signs in macaques include fever, anorexia, depression, facial edema, epistaxis, cutaneous and subcutaneous hemorrhage. Severely elevated LDH, disseminated intravascular coagulation, thrombocytopenia. Some asymptomatic macaques from southeast Asia have antibodies to SHF, suggesting there may be additional viral strains.

Any epizootic of hemorrhagic disease should be reported to the special pathogens branch, Centers for Disease Control, Atlanta, GA.

Pathology: Gross lesions are variable, may be absent, and are seen only in the final stage of disease. Petechial hemorrhage on mucosal and serosal surfaces, hemorrhage and necrosis of the mucosa of the proximal duodenum, splenomegaly, splenic lymphoid follicles ringed with a zone of bright red hemorrhage. Microscopic changes consist of lymphoid necrosis, vasculitis, hemorrhage, and intravascular fibrin deposition (DIC). Large amounts of fibrin are present in splenic cords. Lymphohistiocytic meningoencephalitis occasionally present. Hepatic necrosis with Councilman’s bodies is not a feature of simian hemorrhagic fever, unlike other hemorrhagic fevers. Additionally, in SHF aspartate aminotransferase>alanine aminotransferase, while the reverse is true in the other hemorrhagic fevers.

Palmer AE, et al. Simian hemorrhagic fever. I. Clinical and epizootiologic aspects of an outbreak among quarantined monkeys. Am J Trop Med Hyg 17:404-412, 1968.

Allen AM, et al. Simian hemorrhagic fever. II. Studies in pathology. Am J Trop Med Hyg 17:413-421, 1968.

Tauraso NM, et al. Simian hemorrhagic fever. III. Isolation and characterization of a viral agent. Am J Trop Med Hyg 17:422-431, 1968.

Tauraso NM, et al. Simian hemorrhagic fever. In: Balner H, et al (eds). Infections and immunosuppression in subhuman primates. Williams & Wilkins, 1970.

Abildgaard C, et al. Simian hemorrhagic fever: Studies of coagulation and pathology. Am J Trop Med Hyg 24:537-544, 1975.

Gravel M, et al. Simian hemorrhagic fever: New virus isolated from a chronically infected patas monkey. J Gen Virol 91-106, 1980.

Giddens WE, et al. The pathogenesis of simian hemorrhagic fever: Hematologic and histopathologic studies. Lab Invest 32:424, 1975.

Gravell M, et al. Method to detect asymptomatic carriers of simian hemorrhagic fever virus. Lab Anim Sci 30:988-991, 1980.

Gravell M, et al. Elimination of persistent simian hemorrhagic fever (SHF) virus infection in Patas monkeys. Proc Soc Exp Biol Med 181:219-225, 1986.

Gravell M, et al. Differences among isolates of simian hemorrhagic fever virus. Proc Soc Exp Biol Med 181:112-119, 1986.

London WT. Epizootiology, transmission and approach to prevention of fatal simian hemorrhagic fever in rhesus monkeys. Nature 268:344-345, 1977.

Jahrling PT, et al. Preliminary report: Isolation of Ebola virus from monkeys impoeted to USA. Lancet 335:502-505, 1990.

Renquist D. Outbreak of simian hemorrhagic fever. J Med Primatol 19:77-80, 1990.

Zack PM. Simian hemorrhagic fever. In: Jones TC, et al. (eds). Monographs on pathology of laboratory animals: Nonhuman primates I. Springer-Verlag, 1993, 118-119.

Godeny EK, et al. Molecular characterization of the 3’ terminus of the simian hemorrhagic fever virus genome. J Virol 69:2679-2683, 1995.

Smith SL, et al. Sequence of the 3’ end of the simian hemorrhagic fever virus genome. Gene 191:205-210, 1997.

Etiology: Filovirus related to but antigenically and genetically distinct from African filoviruses (Ebola Zaire, Sudan).

Transmission: Aerosol, contact. Virus shed in urine and oro/nasal secretions. Reservoir unknown.

Clinical: Fatal disease in Philippine cynomolgus monkeys. 5-10% seropositivity in rhesus, African green, and cynomolgus monkeys imported from Africa and Asia (Philippines, Indonesia, Mauritius, China). Humans can become infected, but do not become ill. Must test paired serum - single specimens not useful because low IFA titers are uninterpretable. Fever, weight loss, anorexia, lethargy, coma, hemorrhage, rash, diarrhea. Severely elevated LDH, thrombocytopenia. Survivors clear virus in about 3 weeks. No evidence of persistent infections in monkeys. Healthy monkeys with low titers are probably not infected. African filoviruses (Ebola-Zaire>Ebola-Sudan) are more pathogenic than Asian (Ebola-Reston). African green monkeys are more resistant to disease than macaques.

Pathology: Maculopapular rash, splenomegaly, widespread petechial hemorrhages, hemorrhage in proximal duodenum, interstitial pneumonia. Lymphoid necrosis, massive fibrin deposition in spleen, hepatic necrosis, necrosis of adrenal cortex and pulmonary bronchiolar and alveolar epithelium, interstitial nephritis, amphophilic cytoplasmic inclusion bodies in many tissues including liver, adrenal gland, and spleen. Extensive viral replication in tissue macrophages and interstitial fibroblasts. Much of the necrosis may be secondary to ischemia.

Jahrling PB, et al. Preliminary report: isolation of Ebola virus from monkeys imported to USA. Lancet 335:502-505, 1990.

Centers for Disease Control. Update: Ebola-related filovirus infection in nonhuman primates and interim guidelines for handling nonhuman primates during transit and quarantine. MMWR 39:22-30, 1990.

Centers for Disease Control. Update: Filovirus infection in animal handlers. MMWR 39:17, 1990.

Centers for Disease Control. Update: Filovirus infection associated with contact with nonhuman primates or their tissues. MMWR 39:404-405, 1990.

Dalgard DW, et al. Combined simian hemorrhagic fever and Ebola virus infection in cynomolgus monkeys. Lab Anim Sci 42:152-157, 1992.

Geisbert TW, et al. Association of Ebola-related Reston virus particles and antigen with tissue lesions of monkeys imported into the United States. J Comp Path 106:137-152, 1992.

Preston R. Crisis in the hot zone. New Yorker, Oct 26, 1992, 58-81.

Lecatsas G, et al. Filovirus seropositivity in prospective organ donor baboons. Transplant Proc 42:457, 1992.

Fisher-Hoch SP, et al. Filovirus clearance in non-human primates. Lancet 340:451-453, 1992.

Fisher-Hoch SP, et al. Pathogenic potential of filoviruses: role of geographic origin of primate host and virus strain. J Infect Dis 166:753-763, 1992.

Becker S, et al. Evidence for occurrence of filovirus antibodies in humans and imported monkeys: do subclinical filovirus infections occur worldwide? Med Microbiol Immunol (Berl) 181:43-55, 1992.

Andrie G, et al. Molecular approaches for the treatment of hemorrhagic fever virus infections. Antivir Res 22:45-75, 1993

Centers for Disease Control. Update: Management of patients with suspected viral hemorrhagic fever. MMWR 44:475-479, 1995.

Johnson E, et al. Lethal experimental infections of rhesus monkeys by aerosolized Ebola virus. Int J Exp Path 76:227-236, 1995.

Kalter SS, et al. Detection of Ebola-Reston (Filoviridae) virus antibody by dot-immunobinding assay. Lab Anim Sci 45:523-525, 1995.

Etiology: Marburg virus (filovirus)

Murphy FA, et al. Marburg virus infection in monkeys. Lab Invest 24:279-291, 1971.

Johnson BK, et al. Marburg, Ebola, and Rift Valley Fever virus antibodies in East African Primates. Trans R Soc Trop Med hyg 76:307-310, 1982.

Hennessen W. Epidemiology of Marburg virus disease. In: Balner H, et al (eds). Infections and immunosuppression in subhuman primates. Williams & Wilkins, 1970.

Etiology: Picornavirus

Transmission: fecal-oral

Clinical: Infects humans, chimpanzees, marmosets, owl monkeys, macaques, African green monkeys. Seroconversion and elevation of transaminases are usually the only clinical evidence of infection. Some HAV isolates may be unique to nonhuman primates. Zoonotic potential. A vaccine (Havrix) is available.

Pathology: Periportal and parenchymal mononuclear inflammation, slight focal hepatocellular degeneration and necrosis with acidophilic bodies, Kupfer cell hyperplasia.

Hinthorn DR, et al. An outbreak of chimpanzee associated hepatitis. J Occupational Med 16:388-391, 1974.

Dienstag JL, et al. Nonhuman primate-associated viral hepatitis type A. Serologic evidence of hepatitis A infecton. JAMA 236:462-464, 1976.

Slighter RG, et al. Enzootic hepatitis A infection in Cynomolgus monkeys (Macaca fascicularis). Am J Primatol 14:73-81, 1988.

Keenan CM, et al. Pathology of hepatitis A infection in the owl monkey (Aotus trivirgatus). Am J Pathol 115:1-8, 1984.

Lankas GR, et al. Evidence of hepatitis A infection in immature rhesus monkeys. Vet Pathol 24:340-344, 1987.

Brown EA, et al. Characterization of a simian hepatitis A virus (HAV): Antigenic and genetic comparison with human HAV. J Virol 63:4932-4937, 1989.

Lemon SM, et al. Transmission of hepatitis A virus among recently captured Panamanian owl monkeys. J Med Virol 10:25-36, 1982.

Lemon SM, et al. Genomic heterogeneity among human and nonhuman strains of hepatitis A virus. J Virol 61:735-742, 1987.

Shevtsova ZV, et al. Spontaneous and experimental hepatitis A in old world monkeys. J Med Primatol 17:177-194, 1988.

Abe K, et al. Fulminant type A viral hepatitis in a chimpanzee. Acta Pathol Jpn 32:143-148, 1982.

Etiology: Hepadnavirus

Transmission: Infected blood, saliva, semen. Parenteral inoculation or intimate contact required.

Clinical: Infects human, chimpanzee, gibbon, gorilla, possibly cynomolgus monkey (Macaca fascicularis). Usually no clinical signs other than seroconversion and elevated transaminases. A vaccine is available.

Pathology: Chronic periportal inflammation with focal hepatocyte necrosis.

Kornegay RW, et al. Subacute nonsuppurative hepatitis associated with hepatitis B virus infection in two cynomolgus monkeys. Lab Anim Sci 35:400-404, 1985.

Deinhardt F. Hepatitis in primates. In Lauffer MA, et al. (eds) Adv Virus Res, Academic Press, NY, NY, 20:113-157, 1976.

Eichberg JW, et al. Hepatitis A and B: serologic survey of human and nonhuman primate sera. Lab Anim Sci 30:541-543, 1980.

Popper H, et al. The pathology of viral hepatitis in chimpanzees. Virchows Arch A Path Anat Histol 387:91-106, 1980.

Etiology: Hepatitis C virus

Clinical: Only humans and chimpanzees susceptible.

Abe K, et al. Three different patterns of hepatitis C virus infection in chimpanzees. Hepatol 15:690-695, 1992.

Abe K, et al. Lack of susceptibility of various primates and woodchucks to hepatitis C virus. J Med Primatol 22:433-434, 1993.

Etiology: parvovirus related to human B19 parvovirus.

Clinical: Isolated from cynomolgus monkeys with anemia, but also infected with SRV.

Pathology: Dyserythropoiesis, intranuclear inclusion bodies in bone marrow

O’Sullivan MG, et al. Identification of a novel simian parvovirus in cynomolgus monkeys with severe anemia. J Clin Invest 93:1571-1576, 1994.

Etiology: Rabies virus

Clinical: Only 1 reported spontaneous case.

Boulger LR. Natural rabies in a laboratory monkey. Lancet 1(444):941-943, 1966.

Karasszon D. Experimental infection of rhesus monkeys with Hogyes’ fixed strain of rabies virus. Acta Vet Acad Scien Hungar 19:299-306, 1969.

Wiktor TJ, et al. Role of interferon in prophylaxis of rabies after exposure. J Inf Dis 133(suppl):A260-A265, 1976.

Baer GM, et al. Successful prophylaxis against rabies in mice and rhesus monkeys: the interferon system and vaccine. J Inf Dis 136:286-291, 1977.

Smith RE, et al. Rabies vaccination of captive white-handed gibbons potentially exposed to wild rabies virus. Lab Anim Sci 37:668-669, 1987.

CLASSIFICATION OF RETROVIRUSES:

FAMILY: RETROVIRIDAE

SUBFAMILY: ONCOVIRINAE EXAMPLES

GROUP:

TYPE A Murine intracisternal Type A

TYPE B Mouse mammary tumor virus

TYPE C Avian subgroup: Avian leukosis

Mammalian subgroup: murine leukemia

BLV, HTLV-I&II, STLV-I (have tat gene)

TYPE D MPMV, SAIDS retrovirus, SMRV, PO-1-Lu

SUBFAMILY: LENTIVIRINAE

Visna, Maedi, Ovine Progressive Pneumonia

Caprine Arthritis Encephalitis Virus

Equine Infectious Anemia Virus

Feline T-lymphotropic Virus

Bovine Immunodeficiency-like Virus

Simian Immunodeficiency Virus

Human Immunodeficiency Virus

SUBFAMILY: SPUMAVIRINAE

Foamy viruses

STLV-I (Retroviridae:oncovirinae:Type C)

Simian T-cell leukemia virus (STLV-I) is closely related (90-95% homologous) to the human T-cell leukemia virus type 1 (HTLV-I), the etiologic agent of adult T-cell leukemia/lymphoma, tropical spastic paraparesis, and HTLV-associated myelopathy. There is a high incidence of natural infection in many wild and captive Old World Monkeys, including baboons, African green monkeys, Patas monkeys, various macaques, and chimpanzees. The incidence of infection correlates with age, reaching a peak in animals over 16 years old, and is higher in females than males. Transmission occurs by sexual contact or parenteral inoculation. Neonatal transmission is probably unusual. Persistent infection without seroconversion has not been observed. STLV-I typically infects CD4+ T-cells in macaques and CD8+ T-cells in African monkeys, but some infected T-cell lines express neither marker.

Tsujimoto H, et al. Isolation of simian retroviruses closely related to human T-cell leukemia virus by establishment of lymphoid cell lines from various non-human primates. Int J Cancer 35:377-384, 1985.

Ishida T, et al. A field study of infection with human T-cell leukemia virus among Asian primates. Microbiol Immunol 29:839-846, 1985.

Mone J, et al. Simian T-cell leukemia virus type 1 infection in captive baboons. AIDS Res Hum Retrovir 8:1653-1661, 1992.

Saksena NK, et al. Sequence and phylogenetic analyses of a new STLV-I from a naturally infected tantalus monkey from central Africa. Virol 192:312-320, 1993.

Watanabe T, et al. Sequence homology of the simian retrovirus genome with human T-cell leukemia virus type I. Virol 144:59-65, 1985.

Homma T, et al. Lymphoma in macaques: Association with virus of human T lymphotrophic family. Science 225:716-718, 1984.

Voevodin AF, et al. Antibodies reacting with human T-lymphotropic retrovirus (HTLV-I) or related antigens in lymphomatous and healthy hamadryas baboons. Int J Cancer 36:579-584, 1985.

Tsujimoto H, et al. Development of adult T-cell leukemia-like disease in African green monkey associated with clonal integration of simian T-cell leukemia virus type I. Cancer Res 47:269-274, 1987.

Traina-Dorge V, et al. Immunodeficiency and lymphoproliferative disease in an African green monkey dually infected with SIV and STLV-I. AIDS Res Hum Retrovir 8:97-100, 1992.

Hubbard GB, et al. Spontaneously generated non-Hodgkin’s lymphoma in twenty-seven simian T-cell leukemia virus type I antibody-positive baboons (Papio species). Lab Anim Sci 43:301,309, 1993.

Saksena NK, et al. Seroepidemiologic, molecular, and phylogenetic analyses of simian T-cell leukemia viruses (STLV-I) from various naturally infected monkey species from central and western Africa. Virol 198:1, 1994.

STLV-II - Does not exist as of 6/94. HTLV-II is about 60% related to HTLV-I and STLV-I and may be associated with hairy cell leukemia.

SIMIAN TYPE-D RETROVIRUSES (Retroviridae:oncovirinae:Type D)

SRV Serogroups:

SRV-1: SAIDS/CA, SAIDS/NE

SRV-2: SAIDS/WA, SAIDS/OR (rhesus and Celebes variants)

SRV-3: Mason-Pfizer Monkey Virus

SRV-4: SRV from Cynos at Berkley, CA

SRV-5: SRV from Chinese Rhesus

SRV-Pc: SRV from baboons (Papio cynocephalus)

Squirrel Monkey Endogenous Virus

Langur Endogenous Virus (PO-1-Lu)

Type D retrovirus from talapoins (Miopithecus sp.)

All type D viruses to date are of primate origin. The preferred nomenclature is D/serotype/laboratory/species. Endogenous type D viruses occur in squirrel monkeys and langurs and related proviral sequences have been identified in African and Asian colobines. The endogenous viruses appear to be nonpathogenic. The exogenous viruses infect many species of macaques, naturally-occurring infection in the wild being demonstrated in M. fascicularis (Indonesia, but not those from the Philippines or Seychelles Islands), M. nemestrina (Indonesia), M. radiata (India), M. tonkeana (Sulawesi), and M. mulatta (China). The incidence in captive colonies varies from colony to colony, but can be quite high. Virus can be isolated from peripheral blood mononuclear cells by coculture on Raji cells.

Type D viruses infect B cells, T cells (CD4+ and CD8+), macrophages, epithelial cells (salivary gland, intestine, oral Langerhans cells), and choroid plexus. Vertically infected viremic animals have more widespread provirus than those infected horizontally. Virus is shed in saliva and transmission requires direct physical contact. Biting, licking, and grooming are probably the usual modes of transmission, although vertical transmission also occurs. Some monkeys (probably infected near birth) become persistently infected but antibody negative, serving as healthy carriers. Because of this, animals must be screened repeatedly by ELISA and culture to ensure they are virus-free. Experimental formalin-killed whole virus and recombinant vaccines have been used successfully.

Type D viruses induce an immunosuppressive disease in macaques which may be epizootic in previously naive populations or may be enzootic. Exposed animals may develop an antibody response that clears the infection (although virus negative, antibody positive animals may still harbor virus in bone marrow or gut), may become intermittently virus positive with or without antibodies, or may develop an acute or protracted immunodeficiency disorder with or without fibroproliferative lesions. Retroperitoneal fibromatosis and subcutaneous fibrosarcomas have been associated with SRV-2, may be derived from vascular smooth muscle, and contain virus. Neutropenia, anemia, and terminal lymphopenia are common. Some animals develop persistent generalized lymphadenopathy. Most eventually develop diarrhea, weight loss, bacterial infections, and/or opportunistic infections (CMV, cryptosporidia, Candida, Noma). The clinical outcome in an infected individual is related to the antibody (Ab) response. Monkeys that die early in the course of infection have no Ab and high levels of circulating viral antigen (Ag). Monkeys that survive with persistent viremia make intermediate levels of Ab and have intermediate levels of Ag. Monkeys that clear the infection have high levels of Ab and no Ag. Some animals apparently recover from infection. Neutralizing antibody is thus important in protection against SRV. Lesions that appear to be caused directly by type D viruses include lymphoid hyperplasia which evolves into atrophy, nonsuppurative enteritis, sialoadenitis, and myositis.

SRV-Pc is not known to be pathogenic.

SRV-1, SRV-2, and MPMV have been cloned and sequenced. Several clones are infectious and pathogenic.

Type D virus has very rarely been detected in humans, but the significance of this is unclear. Type D virus infection of humans is very rare to nonexistent.

Fine DL, et al. Type D primate retroviruses: a review. Cancer Res 38:3123-3139, 1978.

Arthur LO, et al. Simian acquired immunodeficiency syndrome. Progr Allergy 37:332-352, 1986.

Marx PA, et al. Mesenchymal neoplasms associated with type D retroviruses in macaques. Cancer Surveys 6:101-115, 1987.

Kwang H-S, et al. Viremia, antigenemia, and serum antibodies in rhesus macaques infected with simian retrovirus type 1 and their relationship to disease course. Lab Invest 56:591-597, 1987.

Spinner A, et al. Simian AIDS ELISA: sensitivity, specificity and predictive values based on a comparison with Western blot technique. Lab Anim Sci 38:568-572, 1988.

Osborn KG, et al. The pathology of an epizootic of acquired immunodeficiency in rhesus macaques. Am J Pathol 114:94-103, 1984.

Tsai C-C, et al. Retroperitoneal fibromatosis and acquired immunodeficiency syndrome in macaques: clinical and immunologic studies. Lab Anim Sci 36:119-125, 1986.

Marx PA, et al. Isolation of a new serotype of simian acquired immune deficiency syndrome type D retrovirus from Celebes black macaques (Macaca nigra) with immune deficiency and retroperitoneal fibromatosis.

Tsai C-C, et al. Subcutaneous fibromatosis associated with an acquired immune deficiency syndrome in pig-tailed macaques. Am J Pathol 120:30-37, 1985.

Giddens WE, et al. Retroperitoneal fibromatosis and acquired immunodeficiency syndrome in macaques. Am J Pathol 119:253-263, 1985.

Marx PA, et al. Prevention of simian acquired immune deficiency syndrome with a formalin-inactivated type D retrovirus vaccine. J Virol 60:431-435, 1986.

Dalakas MC, et al. Polymyositis in an immunodeficiency disease in monkeys induced by a Type D retrovirus. Neurol 36:569-572, 1986.

Lackner AA, et al. Distribution of a macaque immunosuppressive type D retrovirus in neural, lymphoid, and salivary tissues. J Virol 62: 2134-2142, 1988.

Gardner MB, et al. Nonhuman primate retrovirus isolates and AIDS. Adv Vet Sci Comp Med 32:171-226, 1988.

Lowenstine LJ, et al. Retrovirus infections of nonhuman primates: A review. J Zoo Anim Med 19:168-187, 1988.

Schiodt M, et al. Oral lesions in rhesus monkeys associated with infection by simian AIDS retrovirus serotype-1 (SRV-1). Oral Surg Oral Med Pathol 65:50-55, 1988.

Donehower LA, et al. The use of primers from highly conserved pol regions to identify uncharacterized retroviruses by the polymerase chain reaction. J Virol Methods 28:33-46, 1990.

Ilyinskii P, et al. Antibodies to type D retrovirus in talapoin monkeys. J Gen Virol 72:453-456, 1991.

Lowenstine LJ. Type D retrovirus infection, macaques. In: Jones TC, et al. (eds) Monographs on Pathology of Laboratory Animals, Nonhuman Primates I. Springer-Verlag, NY, 1993, 20-32.

Tsai C-C. Fibromatosis in macaques infected with type D retroviruses. In: Jones TC, et al. (eds) Monographs on Pathology of Laboratory Animals: Nonhuman Primates I, Springer-Verlag, 1993, 48-57.

Benveniste RE, et al. Long-term protection of macaques against high-dose type D retrovirus challenge after immunization with recombinant vaccinia virus expressing envelope glycoproteins. J Med Primatol 22:74-79, 1993.

Moazed TC, et al. Viral persistence of simian type D retrovirus (SRV-2/W) in naturally infected pigtailed macaques (Macaca nemestrina). J Med Primatol 22:382-389, 1993.

Lackner AA, et al. Noma, Macaca mulatta. In: Jones TC, et al. (eds). Monographs on pathology of laboratory animals: Nonhuman primates I. Springer-Verlag, 1993, 70-73.

Lerche NW, et al. Establishing specific retrovirus-free breeding colonies of macaques: an approach to primary screening and surveillance. Lab Anim Sci 44:217-221, 1994.

Tsai CC, et al. Immunocytochemistry of Kaposi’s sarcoma-like tumor cells from pigtailed macaques with simian AIDS. J Med Primatol 24:1, 1995.

Grant RF, et al. Characterization of infectious type D retrovirus from baboons. Virol 207:292-296, 1995.

Fikes JD, et al. Localized retroperitoneal fibromatosis causing intestinal obstruction in a cynomolgus monkey (Macaca fascicularis). Vet Pathol 32:713-716, 1995.

Lerche NW, et al. An expanded search for human infection with simian type D retrovirus. AIDS Res Hum Retrovir 11:527-529, 1995.

Wang Y, et al. Use of polymerase chain reaction for diagnosis of type D simian retrovirus infection in macaque blood. Lab Anim Sci 46:187-192, 1996.

Morozov VA, et al. Type D retrovirus markers in healthy Africans from Guinea. Res Virol 147:341-351, 1996.

Kzhyshkowska JG, et al. Markers of thpe D retroviruses in children with Burkitt’s-type lymphoma. Immunol Ltrs 53:101-104, 1996.

PRIMATE LENTIVIRUSES (Retroviridae:lentivirinae)

HUMAN LENTIVIRUSES:

HIV-1 Worldwide

HIV-2 West Africa

NONHUMAN PRIMATE LENTIVIRUSES:

All retroviruses contain env, pol, and gag genes. Lentiviruses have additional regulatory genes: HIV-1/SIV_CPZ contain vif, vpu, vpr, tat, rev, nef; HIV-2/SIV_SMM/SIV_MAC/SIV_MNE/SIV_STM contain vif, vpx, vpr, tat, rev, nef; SIV_AGM contains vif, vpx, tat, rev, nef; SIV_MND contains vif, vpr, tat, rev, nef.

Human Immunodeficiency Virus type I (HIV-1) is the cause of the Acquired Immunodeficiency Syndrome (AIDS) in humans worldwide. The origin of HIV-1 is unknown, but is probably from an African primate. The closest known virus is SIV_cpz. The other SIV’s are much more closely related to HIV-2.

Pigtailed macaques (M. nemestrina) can be acutely infected with high doses of HIV-1 (based on ability to re-isolate virus in culture, detection of HIV-1 gag DNA in PBMC, and persistent seroconversion), but do not become viremic or antigenemic. It is difficult to re-isolate HIV-1 from PBMC after 8 weeks, although viral DNA can be demonstrated. No virus or antibody can be detected in the CSF. Inoculated animals have not become immunodeficient.

Gibbons become persistently infected with HIV-1_IIIB, but do not develop disease. Gibbons are endangered and no research colonies exist, making them useless as an animal model.

Chimpanzees are easily infected with small amounts of HIV-1, seroconvert, and virus can be re-isolated from serum for a few weeks and from PBMC persistently. Chimps develop a broad spectrum antibody response (including antibody-dependent complement-mediated lysis, unlike humans). They do not develop changes in CD4+ lymphocytes or immune function, and do not develop opportunistic infections or other signs of disease. Chimpanzee monocytes/macrophages are resistant to HIV infection, although this can be overcome by in vivo passage. Although chimp CD4+ lymphocytes are readily infected, they produce less virus than human cells. Chimps have more CD8+ suppressor cells than humans. There is not an increased level of apoptosis (programmed cell death) in lymphocytes from HIV infected chimps and their T_H cells are not susceptible to gp120 induced anergy. Chimpanzees have strong lymphokine-activated killer (LAK) cell activity, which humans do not. Chimps do not demonstrate gp120-specific antibody-dependent cellular cytotoxicity (ADCC). They do not show cytotoxic T-lymphocyte (CTL) activity. HIV infection does not appear to cause chronic lymphocyte activation in chimps. Only HIV_Lai(IIIb) has been titrated in chimpanzees. Additional titrated stocks are needed for challenge studies. About 150 chimps have been infected. Provisions for retirement of infected animals must be made.

Lusso P, et al. Cell-mediated immune response toward viral envelope and core antigens in gibbon apes (Hylobates lar) chronically infected with human immunodeficiency virus-1. J Immunol 141:2467-2473, 1988.

Frumkin LR, et al. Acute infection of Macaca nemestrina by human immunodeficiency virus type 1. Virol 195:422-431, 1993.

Gardner MB, et al. Animal models of AIDS. FASEB J 3:2593-2606, 1989.

Prince AM, et al. Appropriate conditions for maintenance of chimpanzees in studies with blood-borne viruses: An epidemiologic and psychosocial perspective. J Med Primatol 18:27-42, 1989.

Heeney J, et al. The resistance of HIV-infected chimpanzees to progression to AIDS correlates with absence of HIV-related T-cell dysfunction. J Med Primatol 22:194-200, 1993.

Dirienzo AM, et al. Different proliferative response of human and chimpanzee lymphocytes after contact with human immunodeficiency virus type 1 gp120. European J Immunol 24:34-40, 1994.

Human Immunodeficiency Virus type 2 (HIV-2) (previously HTLV-IV) is the cause of AIDS, or "slim" disease, in western Africa, with little international spread. HIV-2 is apparently less pathogenic than HIV-1. Viral load is lower in HIV-2 infected people than in HIV-1 infected people, until immunosuppression is severe. This may be the reason heterosexual and perinatal infection with HIV-2 is less efficient until the terminal stages of AIDS. HIV-2 is closely related to SIV_sm, and may belong to a single, highly diverse group which cannot be separated into distinct phylogenetic lineages by species of origin. The sooty mangabey may be the natural reservoir and human infection may be a zoonosis.

Macaques and baboons can be infected, but HIV-2 infrequently induces disease in macaques and not at all in baboons.

Gao F, et al. Human infection by genetically diverse SIV_sm-related HIV-2 in west Africa. Nature 358:495-499, 1992.

Dormont D, et al. HIV-2 in rhesus monkeys: serological, virological, and clinical results. Intervirol 30 (Suppl):59-65, 1989.

Letvin NL, et al. Infection of baboons with human immunodeficiency virus-2 (HIV-2). J Inf Dis 156:406-407, 1987.

Franchini G, et al. Persistent infection of rhesus macaques with a molecular clone of human immunodeficiency virus type 2: Evidence of minimal genetic drift and low pathogenetic effects. J Virol 64:4462-4467, 1990.

Simian Immunodeficiency Viruses (SIV) (previously STLV-III) are comprised of six groups (HIV-2/SIV_SMM/SIV_MAC/SIV_STM/SIV_MNE; HIV-1/SIV_CPZ; SIV_AGM/SIV_WCM; SIV_MND; SIV_{RCM and} SIV_SYK) of related viruses that occur naturally and are indigenous in some African primates, including Cercopithecus sp. (African green monkeys, vervets, grivets, tantalus monkeys, Sykes monkeys), Papio sp. (mandrills and anubis), Cercocebus sp. (sooty, red capped, and white crowned mangabeys), and Pan troglodytes (chimpanzee). Other, presently uncharacterized, SIVs are known to exist in other species. These animals are persistently infected, but appear to remain asymptomatic for life. SIV_AGM is the most genetically diverse group and has co-evolved with the 4 geographically separate subspecies of African green monkeys (vervets, grivets, tantalus, sabaeus) indicating SIV has been present in this species for a very long time. The natural route of transmission is unknown. Persistent infection without seroconversion has been observed in sooty mangabeys.

The reasons the natural hosts remain asymptomatic while heterologous hosts develop fatal immunodeficiency is an area of active research. Disease progression in all species appears to be related to virus load. Viral replication occurs throughout the clinically latent period of infection. Humans typically initially respond to HIV with a vigorous cytotoxic T lymphocyte (CTL) and antibody-dependent cellular cytotoxicity (ADCC) response, but with weak neutralizing antibody and little complement activating antibody. SIV infected African green monkeys and sooty mangabeys (the natural hosts) also respond with little neutralizing or complement activating antibody. The antibody response is primarily anti-env, with little anti-gag. Viral load in African green monkeys is comparable to that in asymptomatic HIV-1 infected people, while sooty mangabeys carry higher viral loads. Such studies indicate that pathogenicity does not lie in the virus alone, or in a particular gene, but in the virus/host system. HIV-1/SIV_MAC and HIV-1/SIV_AGM chimeras have been constructed and are being used to understand the molecular functions of each virus.

SIV has also been isolated from several species of macaques (M. mulatta, M. nemestrina, M. fascicularis, M. arctoides) housed in laboratories. SIV does not infect Asian monkeys in the wild. SIV_MAC is closely related to SIV_SMM and probably represents a cross-species infection that occurred in captivity. SIV_SMM is probably the progenitor of SIV_MAC, SIV_MNE, SIV_STM, and HIV-2. SIV_MAC and SIV_SMM are highly pathogenic to macaques, producing an immunodeficiency disease. SIV_AGM is much less pathogenic in macaques, although disease has been produced in M. nemestrina.

Because of the similarities to human AIDS, the SIV infected macaque has been widely used as an animal model to study pathogenesis, immunoprophylaxis, therapy, and vertical transmission. As with any model however, there are some dissimilarities and other factors to be aware of when interpreting research results. As examples, retroviral syncytial cells are seen commonly only in the CNS of AIDS patients, whereas they are frequently widespread in terminally ill SIV-infected macaques. The entire spectrum of neurological lesions seen in AIDS encephalitis has not been reproduced with SIV. SIV has no variability in the V3 loop of the envelope protein, whereas HIV-1 V3 is hypervariable and contains the principal neutralizing domain. This may be important for env based vaccines and immune recognition of env products may be very important in low dose mucosal exposures. SIV grown on human cell lines acquires human cellular antigens as it buds through the cell membrane. When such virus is used in vaccine preparations or challenge inocula, the macaque immune system responds to these, providing some protection against infection. This situation has caused the success of early vaccine trials to be re-evaluated.

A few laboratory workers have seroconverted to SIV and virus (SIV_HU) has been isolated from one. To date, viral load is low and the worker is asymptomatic with normal immune function. The natural history of SIV infection in man remains unknown. SIV is a zoonotic agent!

Animal models for HIV infection and AIDS: Memorandum from a WHO meeting. Bull WHO 66:561-574, 1988.

Baskin GB, et al. Necropsy findings in rhesus monkeys experimentally infected with cultured simian immunodeficiency virus (SIV)/Delta. Vet Pathol 25:456-467, 1988.

Zhang J, et al. Simian Immunodeficiency Virus/Delta-induced immunodeficiency disease in rhesus monkeys: Relation of antibody response and antigenemia. J Inf Dis 158:1277-1286, 1988.

Benveniste RE, et al. Inoculation of baboons and macaques with Simian Immunodeficiency Virus/Mne, a primate lentivirus closely related to Human Immunodeficiency Virus Type 2. J Virol 62:2091-2101, 1988.

Tsujimoto H, et al. Isolation and characterization of simian immunodeficiency virus from mandrills in Africa and its relationship to other human and simian immunodeficiency viruses. J Virol 62:4044-4050, 1988.

Desrosiers RC. Simian immunodeficiency viruses. Ann Rev Microbiol 42:607-625, 1988.

Schneider J, et al. Editorial Review. Simian lentiviruses - the SIV group. AIDS 2:1-9, 1988.

Chalifoux LV, et al. Lymphadenopathy in macaques experimentally infected with the Simian Immunodeficiency Virus (SIV). Am J Pathol 128:104-110, 1987.

Chalifoux LV, et al. Lymphoproliferative syndrome in an immunodeficient rhesus monkey naturally infected with an HTLV-III-like virus (STLV-III). Lab Invest 55:43-50, 1986.

Ohta Y, et al. Isolation of simian immunodeficiency virus from African green monkeys and seroepidemiologic survey of the virus in various non-human primates. Int J Cancer 41:115-122, 1988.

Ringler DJ, et al. An erythematous maculopapular eruption in macaques infected with an HTLV-III-like virus (STLV-III). J Invest Dermatol 87:674-677, 1986.

Hayami M, et al. Detection of antibodies to Human T-lymphotropic Virus Type III in various nonhuman primates. Japan J Exp Med 55:251-255, 1985.

Ringler DJ, et al. Simian Immunodeficiency Virus-Induced meningoencephalitis: Natural history and retrospective study. Ann Neurol 23(suppl):S101-S107, 1988.

Sharer LR, et al. Comparison of Simian Immunodeficiency Virus and Human Immunodeficiency Virus encephalitides in the immature host. Ann Neurol 23(suppl):S108-S112, 1988.

Baskin GB. Disseminated cytomegalovirus infection in immunodeficient rhesus monkeys. Am J Pathol 129:345-352, 1987.

Blanchard JL, et al. Trichomonas gastritis in rhesus monkeys infected with the Simian Immunodeficiency Virus. J Inf Dis 157:1092-1093, 1988.

Blanchard JL, et al. Disseminated cryptosporidiosis in Simian Immunodeficiency Virus/Delta-infected rhesus monkeys. Vet Pathol 24:454-456, 1987.

Lowenstine LJ, et al. Seroepidemiologic survey of captive old-world primates for antibodies to human and simian retroviruses, and isolation of a lentivirus from sooty mangabeys (Cercocebus atys). Int J Cancer 38:563-574, 1986.

King NW. Simian models of Acquired Immunodeficiency Syndrome (AIDS): A review. Vet Pathol 23:345-353, 1986.

Desrosiers RC, et al. Animal models for Acquired Immunodeficiency Syndrome. Rev Inf Dis 9:438-446, 1987.

Baskin GB, et al. Transmissible lymphoma and simian acquired immunodeficiency syndrome in rhesus monkeys. J Natl Cancer Inst 77:127-139, 1986.

Murphey-Corb M, et al. Isolation of an HTLV-III-related retrovirus from macaques with simian AIDS and its possible origin in asymptomatic mangabeys. Nature 321:435-437, 1986.

Letvin NL, et al. Induction of AIDS-like disease in macaque monkeys with T-cell tropic retrovirus STLV-III. Science 230:71-73, 1985.

Lecatsas G, et al. Morphology of the retroviruses associated with AIDS and SAIDS. Proc Soc Exp Biol Med 177:495-498, 1984.

Lowenstine LJ, et al. Retrovirus infections of nonhuman primates: A Review. J Zoo Anim Med 19:168-187, 1988.

Kraus G, et al. Isolation of human immunodeficiency virus-related simian immunodeficiency viruses from African green monkeys. Proc Natl Acad Sci USA 86:2892-2896, 1989.

Tsujimoto H, et al. Isolation and characterization of simian immunodeficiency virus from mandrills in Africa and its relationship to other human and simian immunodeficiency viruses. J Virol 62:4044-4050, 1988.

Fultz PN, et al. Identification and biologic characterization of an acutely lethal variant of simian immunodeficiency virus from sooty mangabeys (SIV/SMM). AIDS Res Hum Retrovir 5:397-409, 1989.

Peeters M, et al. Isolation and partial characterization of an HIV-related virus occurring naturally in chimpanzees in Gabon. AIDS 3:625-630, 1989.

Huet T, et al. Genetic organization of a chimpanzee lentivirus related to HIV-1. Nature 345:356-359, 1990.

Herchenroder O, et al. Experimental infection of rhesus monkeys with SIV isolated from African green monkeys. Invervirol 30(suppl 1):66-72, 1989.

Villinger F, et al. Detection of occult simian immunodeficiency virus SIVsmm infection in asymptomatic seronegative nonhuman primates and evidence for variation in SIV gag sequence between in vivo and in vitro propagated virus. J Virol 65:1855-1862, 1991.

Allan JS, et al. Species-specific diversity among simian immunodeficiency viruses from African green monkeys. J Virol 65:2816-2828, 1991.

Khan AS, et al. A highly divergent simian immunodeficiency virus (SIV_stm) recovered from stored stump-tailed macaque tissues. J Virol 65:7061-7065, 1991.

Emau P, et al. Isolation from African Sykes’ monkeys (Cercopithecus mitis) of a lentivirus related to human and simian immunodeficiency viruses. J Virol 65:2135-2140, 1991.

Muller MC, et al. Simian immunodeficiency viruses from central and western Africa. Evidence for a new species-specific lentivirus in tantalus monkeys. J Virol 67:1227-1235, 1993.

King NW. Simian immunodeficiency virus infections. In: Jones TC, et al. (eds) Monographs on Pathology of Laboratory Animals: Nonhuman Primates I, Springer-Verlag, 1993, 5-20.

Cichutek K, et al. Lack of immune suppression in SIV-infected natural hosts. AIDS 7(suppl 1:25-35, 1993.

Wyand MS. The use of SIV-infected rhesus monkeys for the preclinical evaluation of AIDS drugs and vaccines. AIDS Res Hum Retrovir 8:349-356, 1992.

Putkonen P, et al. Whole inactivated SIV vaccine grown on human cells fails to protect against homologous SIV grown on simian cells. J Med Primatol 22:100-103, 1993.

Javaherian K, et al. The principal neutralization determinant of simian immunodeficiency virus differs from that of human immunodeficiency virus type 1. Proc Natl Acad Sci USA 89:1418-1422, 1992.

Warren JT, et al. First updated and revised survey of worldwide HIV and SIV vaccine challenge studies in nonhuman primates: Progress in fiirst and second order studies. J Med Primatol 22:203-235, 1993.

Khabbaz RF, et al. Simian immunodeficiency virus needlestick accident in a laboratory worker. Lancet 340:271-273, 1992.

Khabbaz RF, et al. Infection of a laboratory worker with simian immunodeficiency virus. NEJM 330a:172-177, 1994.

Essex M. Simian immunodeficiency virus in people. NEJM 330:209-210, 1994.

Simon MA, et al. Immunopathogenesis of SIVmac. Virus Res 32:227-251, 1994.

Hirsch VM, et al. Pathogenic diversity of simian immunodeficiency viruses. Virus Res 32:183-203, 1994.

Hirsch VM, et al. Phylogeny and natural history of the primate lentiviruses, SIV and HIV. Current Opinion in Genetics & Development 5:798-806, 1995.

The foamy viruses are nonpathogenic, but are prevalent and widespread in the tissues of macaques and other primates. They cause life-long infections in monkeys and some are transmissible through sexual contact, blood, or breast-feeding. Humans have become infected with nonhuman primate spumaviruses.

Foamy viruses frequently contaminate primary cell cultures, particularly kidney and lymphocyte, and should not be mistaken for other agents. Foamy virus produces vacuolated multinucleated cells in many cultures, mimicing the CPE of other viruses. The RT characteristics are similar to lentiviruses. By TEM, spumaviruses are morphologically distinct from other retroviruses because they are decorated with prominent radially arranged spikes.

Nara PL, et al. Simultaneous isolation of simian foamy virus and HTLV-III/LAV from chimpanzee lymphocytes following HTLV-III or LAV inoculation. Arch Virol 92:183-186, 1987.

Swack NS, et al. Pathogenesis of simian foamy virus infection in natural and experimental hosts. Inf Immun 12:470-474, 1975.

Swack NS, et al. Foamy virus infection of rhesus and green monkeys in captivity. Am J Epidemiol 92:79-83, 1970.

Aguzzi A. The foamy virus family: molecular biology, epidemiology, and neuropathology. Biochemica et Biophysica Acta 1155:1-24, 1993.

CDC. Nonhuman primate spumavirus infections among persons with occupational exposure - United States, 1996. MMWR 46:129-131, 1997.

Broussard SR, et al. Characterization of new simian foamy viruses from African nonhuman primates. Virology 237:349-359, 1997.

Bons N, et al. Spontaneous spongiform encephalopathy in a young adult rhesus monkey. CR Acad Sci Paris 319:733-736, 1996. Lancet 348:55, 1996. Lancet 348:956, 1996.

Etiology: Candida albicans

Transmission: Ubiquitous organism. Opportunistic infection of immunocompromised animals.

Clinical: Occurs in debilitated animals or animals on long-term antibiotics. Dysphagia, white pseudomembrane on oral mucous membranes.

Pathology: White pseudomembrane on oral and esophageal mucous membranes. Underlying tissue may be ulcerated. Organism can be seen on HE, but best studied with PAS or GMS stains. Septate pseudohyphae and oval budding blastospores in superficial epithelium. Rarely invade past basement membrane.

Migaki G, et al. Mycotic infections of the alimentary tract of nonhuman primates: A review. Vet Pathol 19(Suppl 7):93-103, 1982.

McCullough B, et al. Multifocal candidiasis in a capuchin monkey (Cebus apella). J Med Primatol 6:186-191, 1977.

Etiology: Pneumocystis carinii (now considered a lower fungus). May be species specific.

Transmission: aerosol

Clinical: Horizontally acquired or reactivated latent infections in immunodeficient animals. Fever, dyspnea, cough.

Pathology: Lesions usually restricted to lung, but generalized infections have been described in severely immunodeficient humans. Foamy eosinophilic intra-alveolar exudate mixed with alveolar macrophages, interstitial lymphocytic infiltration, hypertrophy of alveolar lining cells. Organisms in exudate and along alveolar walls. Cysts demonstrable with GMS stain.

Matsumoto Y, et al. Pneumocystis infection in macaque monkeys: Macaca fuscata fuscata and Macaca fascicularis. Parasitol Res 73:324-327, 1987.

Chandler FW, et al. Pulmonary pneumocystosis in nonhuman primates. Arch Pathol Lab Med 100:163-167, 1976.

Long GG, et al. Pneumocystis carinii infection in splenectomized owl monkeys. J Am Vet Med Assn 167:651-654, 1975.

Richter CB, et al. Endemic Pneumocystis carinii in a marmoset colony. J Comp Pathol 88:171-180, 1978.

Nouza M. Pneumocystis carinii pneumonia after 40 years. Infection 20:113-117, 1992.

Vogel P, et al. Evidence of horizontal transmission of Pneumocystis carinii pneumonia in simian immunodeficiency virus-infected rhesus macaques. J Inf Dis 168:836-843, 1993.

Furuta T, et al. Severe pulmonary pneumocystosis in simian acquired immunodeficiency syndrome induced by simian immunodeficiency virus: its characterization by the polymerase chain reaction method and failure of experimental transmission to immunodeficient animals. Parasitol Res 79:624-628, 1993.

Etiology: Histoplasma capsulatum var capsulatum, Histoplasma capsulatum var duboisii (African histoplasmosis)

Transmission: Inhalation of spores of H capsulatum from soil rich in bird or bat excreta. H. duboisii may be spread by dermal contact and may have a long incubation period.

Clinical: H. capsulatum: Infection is usually latent. Clinical disease can occur with heavy exposure, resulting in influenza-like disease, with pre-existing lung lesions, or disseminated disease can result from immunodeficiency. Rare in monkeys.

H. duboisii. Reported only from Africa in humans and baboons. Affects skin, lymph node, and bone.

Baskin GB. Disseminated histoplasmosis in a SIV-infected rhesus monkey. J Med Primatol 20:251-253, 1991.

Weller RE, et al. Hypercalcemia and disseminated histoplasmosis in an owl monkey. J Med Primatol 19:675-680, 1990.

Butler TM, et al. Case of disseminated African histoplasmosis in a baboon. J Med Primatol 17:153-161, 1988.

Walker J, et al. Natural infection of the African baboon, Papio papio, with the large-cell form of Histoplasma. J Path Bact 80:436-438, 1960.

Butler TM, et al. An epizootic of Histoplasmosis duboisii (African histoplasmosis) in an American Baboon colony. Lab Anim Sci 41:407-410, 1991.

Migaki G, et al. Histoplasma capsulatum var. duboisii infection, baboon. In: Jones TC, et al. (eds) Monographs on Pathology of Laboratory Animals: Nonhuman Primates II, Springer-Verlag, 1993, 19-23.

Etiology: Blastomyces dermatiditis

Transmission: Inhalation.

Clinical: Usually affects lung, skin, & bone. Papules or draining abscesses on skin. Seen occasionally in outdoor housed monkeys in US.

Etiology: Coccidioides immitis

Transmission: Inhalation of spores.

Clinical: The disease is limited to arid regions of North & South America. Infection is usually subclinical, but respiratory disease or dissemination, particularly to bone, may occur.

Pathology: Necropurulent granulomatous inflammation. Double contoured 20-80m spherules that may contain smaller endospores.

Beaman L, et al. The incidence of coccidioidomycosis among nonhuman primates housed outdoors at the California Primate Research Center. J Med Primatol 9:254-261, 1980.

Castleman WL, et al. Posterior paralysis and spinal osteomyelitis in a rhesus monkey with coccidioidomycosis. J Am Vet Med Assn 177:933-934, 1980.

Etiology: Cryptococcus neoformans

Transmission: Inhalation

Clinical: CNS and ocular abnormalities usually.

Garner FM, et al. A systemic cryptococcosis in 2 monkeys. J Am Vet Med Assn 155:1163-1168, 1969.

Sly DL, et al. Disseminated cryptococcosis in a patas monkey (Erythrocebus patas). Lab Anim Sci 27:694-699, 1977.

Takos MJ, et al. Spontaneous cryptococcosis of marmoset monkeys in Panama. Arch Pathol 55:403-407, 1953.

Baskin GB, et al. Cutaneous zygomycosis in rhesus monkeys (Macaca mulatta). Vet Pathol 21:125-128, 1984.

Fleischman RW, et al. Paecilomycosis in a nonhuman primate (Macaca mulatta). Vet Pathol 14:387-391, 1977.

Dolensek EP, et al. Gastrointestinal geotrichosis in six adult gorillas. J Am Vet Med Assn 171:975-976, 1977.

Hessler JR, et al. Mucormycosis in a rhesus monkey. J Am Vet Med Assn 151:909-913, 1967.

Martin JE, et al. Rhino-orbital phycomycosis in a rhesus monkey (Macaca mulatta). J Am Vet Med Assn 155:1253-1257.

Lucke VM, et al. Phycomycosis in a mandrill (Mandrillus sphinx). Vet Rec 77:1306-1310, 1965.

Gisler DB, et al. Intestinal mucormycosis in the monkey (Macaca mulatta). Am J Vet Res 23:365-367, 1962.

Roy AD, et al. Rhinophycomycosis entomophthorae occurring in a chimpanzee in the wild in East Africa. Am J Trop Med Hyg 21:234-237, 1972.

Migaki G, et al. Disseminated entomophthoromycosis in a mandrill (Mandrillus sphinx). Vet Pathol 19:551-554, 1982.

Migaki G, et al. Mycotic infections of the alimentary tract of nonhuman primates: A review. Vet Pathol 19(Suppl. 7):93-103, 1982.

Etiology: Unknown, Shigella sp. occasionally, NOMA associated with SAIDS.

Clinical: Usually none. Animals often debilitated or immunosuppressed due to other causes. Associated with dental calculus.

Pathology: Lesions vary from slight reddening of gums to necrotizing ulcerative gingivitis. Gingival bleeding common. Interproximal craters with alveolar bone destruction in severe cases. Spirochetes can be demonstrated in gingival connective tissue by silver staining. Shigella flexneri, serotype 4 is commonly present. Gangrenous necrosis of bone and overlying soft tissues in NOMA (Cancrum oris) - associated with type D retrovirus infection.

Cohen DW. Oral disease in primates. Ann NY Acad Sci 85:889-909, 1960.

Buchanan W, et al. NOMA in a nonhuman primate: Oral Surgery, Oral Med, Oral Path 52:19-22, 1981.

Adams RJ, et al. An oral disease resembling NOMA in six rhesus monkeys. Lab Anim Sci 30:85-91, 1980.

Brack M. NOMA in Saguinus oedipus: A report of two cases. Lab Anim 16:361-363, 1982..

Curtis J, et al. Periapical abscesses of cut canine teeth in cynomolgus macaques. Lab Anim 20:277-280, 1986.

Schou S, et al. Non-human primates used in studies of periodontal disease pathogenesis: A review of the literature. J Periodontol 64:497-508, 1993.

Armitage GC, et al. Gingivitis, necrotizing ulcerative, Macaca mulatta. In: Jones TC, et al. (eds) Monographs on Pathology of Laboratory Animals: Nonhuman Primates II, Springer-Verlag, 1993, 27-29.

Schiodt M, et al. Oral lesions in rhesus monkeys associated with infection by simian AIDS retrovirus serotype-1 (SRV-1). Oral Surg Oral Med Pathol 65:50-55, 1988.

Etiology: Unknown. May be a sequela to chronic gingivitis. Possibly familial in macaques. Phenytoin may also produce gingival enlargement.

Clinical: Usually none.

Pathology: Mild to marked firm enlargement of the marginal and alveolar gingiva, including the interdental papillae. The hyperplastic tissue is normal in color and may completely cover the teeth. Microscopically, the tissue is dense collagen with little inflammation.

Schiodt M, et al. Gingival fibromatosis, Macaca mulatta. In: Jones TC, et al. (eds) Monographs on Pathology of Laboratory Animals: Nonhuman Primates II, Springer-Verlag, 1993, 30-31.

Etiology: Thought to be multifactorial including food restriction, overeating, anesthesia. Usually occurs in caged monkeys. Clostridium perfringens Type A can be isolated in large numbers and may be responsible for gas production.

Clinical: OWM and NWM. Usually found dead. Abdomen enlarged and taut.

Pathology: Stomach markedly distended with gas and brown watery fluid, intestine congested. Subcutaneous emphysema occurs if the stomach ruptures. Affected monkeys die of respiratory embarrassment, impaired venous return, and shock.

Stein FH, et al. Acute gastric dilatation in common marmosets. Lab Anim Sci:522-523, 1981.

Bennett B, et al. Acute gastric dilatation in monkeys: a microbiologic study of gastric contents, blood, and feed. Lab Anim Sci 30:241-244, 1980.

Chapman WL. Acute gastric dilatation in Macaca mulatta and Macaca speciosa monkeys. Lab Anim Care 17:130-136, 1967.

Christie RJ, et. al Acute gastric dilatation and rupture in Macaca arctoides associated with Clostridium perfringens. J Med Primatol 10:263-264, 1981.

Pond CL, et al. Acute gastric dilatation in nonhuman primates: Review and case studies. Vet Pathol 19:126-133, 1982.

Newton WM, et al. Acute bloat syndrome in stumptailed macaques: A report of four cases. Lab Anim Sci 21:193-196, 1971.

Etiology: Congenital? Spastic contraction of the colon?

Clinical: Usually none. Abdominal pain.

Pathology: Saccular protrusions along taenia coli, muscular hypertrophy. May become impacted and inflamed.

Etiology: Unknown.

Clinical: Squirrel monkeys and marmosets: Ascites, congestive heart failure, posterior paralysis. Great Apes: Common from middle age onward, associated with obesity. May cause no clinical signs or sudden death, especially during anesthesia. Also common in old macaques, but seldom causes clinical disease.

Pathology: Cardiomegaly, myocardial hypertrophy, fibrosis, atrial thrombosis, saddle thrombus in aorta, ascites, pulmonary edema in New World Monkeys. Myocardial fibrosis and hypertrophy in apes.

Schulman FY, et al. Fibrosing cardiomyopathy in captive western lowland gorillas (Gorilla gorilla gorilla) in the United States: A retrospective study. J Zoo Wildlife Med 26:43-51, 1995.

Etiology: Unknown.

Clinical: Rhesus, all ages. Chronic diarrhea, weight loss, hepatomegaly, often associated with osteoarthritis.

Pathology: Amyloid deposition in spleen, lymph nodes, liver, lamina propria of gastrointestinal tract. Often nonspecific chronic inflammation in colon. Lymphoid atrophy.

Gribble DH. Granulomatous enteritis and intestinal amyloidosis in nonhuman primates. Path Vet 9:81-82, 1972.

Casey HW, et al. Generalized amyloidosis in a rhesus monkey. Lab Anim Sci 22:587-593, 1972.

Chapman WL, et al. Amyloidosis in rhesus monkeys with rheumatoid arthritis and enterocolitis. JAVMA 171:855-858, 1977.

Benditt EP, et al. Chemical characteristics of the substance of typical amyloidosis in monkeys. Acta Path Microbiol Scand 80: suppl 233:103-108, 1972.

Blanchard J, et al. Amyloidosis in rhesus monkeys. Vet Pathol 23:425-430, 1986.

Slattum MM, et al. Amyloidosis in pigtailed macaques (Macaca nemestrina): Pathologic aspects. Lab Anim Sci 39:567-570, 1989.

Ellsworth L, et al. Factors associated with intestinal amyloidosis in pigtailed macaques (Macaca nemestrina). Lab Anim Sci 42:352-355, 1992.

Blanchard JL. Generalized amyloidosis, nonhuman primates. Monographs on Pathology of Laboratory Animals: Nonhuman Primates I, Springer-Verlag, 1993, 194-197.

Etiology: Unknown.

Clinical: Diabetes mellitus. Macaca nigra and Macaca fascicularis have higher incidence.

Pathology: Amyloidosis of Islets of Langerhans. Not associated with amyloid deposition in other organs.

Palotay JL, et al. Insular amyloidosis in spontaneously diabetic nonhuman primates. Vet Pathol 19(Suppl 7):181-192, 1982.

Cromeens DM, et al. Insular amyloidosis and diabetes mellitus in a crab-eating macaque (Macaca fascicularis). Lab Anim Sci 35:642-645, 1985.

Howard CF. The insular amyloidotic lesion and its relationship to diabetes mellitus, Macaca nigra. In: Jones TC, et al. (eds). Monographs on pathology of laboratory animals: Nonhuman primates II. Springer-Verlag, 1993, 197-202.

Wagner JD, et al. Diabetes mellitus and islet amyloidosis in cynomolgus monkeys. Lab Anim Sci 46:36-41, 1996.

Etiology: Kaolin containing antidiarrheals aspirated or delivered subcutaneously or peritracheally.

Clinical: Pneumonia, swelling in throat area.

Pathology: Macrophages filled with birefringent crystals of kaolin in lung or peritracheal tissues.

Etiology: Unknown.

Clinical: None. Rhesus and stumptails (M. arctoides).

Pathology: Irregular eccentric nodular thickenings in walls of medium sized arteries in renal cortex, composed of proliferating cells in tunica media. Sometimes occur in whorls, with gaps in the internal elastic membrane. Mononuclear inflammatory cells are in the adventitia. No other associated lesions.

Beach JE., et al. An unusual form of proliferative arteriopathy in macaque monkeys. Exp Molec Pathol 21:322-338, 1974.

Etiology: Unknown.

Clinical: High incidence in cotton-top tamarin (Saguinus oedipus oedipus). Diarrhea, weight loss, intestinal obstruction, palpable abdominal mass.

Pathology: Carcinomas arise in association with preexisting chronic ulcerative colitis. Poorly differentiated mucinous carcinomas, usually in structureless masses. Early lesions best demonstrated with PAS. Often multiple, often metastasize.

References:

Chalifoux LV, et al. An analysis of the association of gastroenteric lesions with chronic wasting syndrome of marmosets. Vet Pathol 19:141-162, 1982.

Chalifoux LV, et al. Colonic adenocarcinoma associated with chronic colitis in cotton top marmosets. Gastroenterology 80:942-946, 1981.

Lushbaugh CC, et al. Spontaneous colonic adenocarcinoma in marmosets. Prim Med 10:119-134, 1978 (Karger, Basel).

Dufrain RJ. Is cancer of the colon familial in cotton-top tamarins? Cancer Genetics and Cytogenetics l4:83-87, 1985.

Lushbaugh C, et al. Histology of colon cancer in Saguinus oedipus oedipus. Digestive Dis Sci 30:119s-125s, 1985.

Lushbaugh C, et al. Histology of colitis: Saguinus oedipus oedipus and other marmosets. Digestive Dis Sci 30:45s-51s, 1985.

Russel RG, et al. Coronavirus-like particles and Campylobacter in marmosets with diarrhea and colitis. Digestive Dis Sci 30: 72s-77s, 1985.

Estes MK. Evaluating viral agents in marmoset colitis. Digestive Dis Sci 30:80s-81s, 1985.

Clapp NK, et al. Natural history and pathology of colon cancer in Saguinus oedipus. Digestive Dis Sci 30:107s-113s, 1985.

Yardley JH. Comments on comparative pathology of colonic neoplasia in cotton top marmosets. Digestive Dis Sci 30:126s-133s, 1985.

Kirkwood JK, et al. Adenocarcinoma of the large bowel and colitis in captive cotton-top tamarins. J Comp Pathol 96:507-515, 1986.

Chalifoux LV, et al. Adenocarcinoma, colon, cotton-top tamarin. In: Jones TC, et al. (eds). Monographs on pathology of laboratory animals: Nonhuman primates II. Springer-Verlag, 1993, 87-94.

Wood JD, et al. Colitis and colon cancer in cotton-top tamarins (Saguinus oedipus oedipus) living wild in their natural habitat. Digest Dis Sci 43:1443-1453, 1998.

Etiology: Implantation of normal endometrial tissue in ectopic locations. Thought to occur through retrograde menstruation.

Clinical: Depends on site of implantation. Abdominal swelling, constipation, uremia.

Pathology: Multiple cysts which contain "chocolate brown" fluid, extensive fibrosis, hemosiderosis, and adhesions. The lower abdominal and pelvic organs are often adhered into a single mass. Can cause obstruction of intestine and ureters. Histologically endometrial epithelium and stroma must be present to differentiate endometriosis from endometrial carcinoma. Dense fibrosis and hemosiderosis are usually present.

Bertens APMG, et al. Endometriosis in rhesus monkeys. Lab Anim 16:281-284, 1982.

McCann TO, et al. Endometriosis in rhesus monkeys. Am J Obstet & Gynecol 106:516-523,1970.

Splitter GA, et al. Endometriosis in four irradiated rhesus monkeys. Vet Pathol 9:249-262, 1972.

Schenken RS, et al. Etiology of infertility in monkeys with endometriosis: measurement of peritoneal fluid prostaglandins. Am J Obstet & Gynecol 150:349-353, 1984.

Lindberg BS, et al. Endometriosis in rhesus monkeys. Upsala J Med Sci 89:129-134, 1984.

Fanton JW, et al. Endometriosis: Clinical and pathologic findings in 70 rhesus monkeys. Am J Vet Res 47:1537-1541, 1986.

Fanton JW, et al. Surgical treatment of endometriosis in 50 rhesus monkeys. Am J Vet Res 47:1602-1604, 1986.

Etiology: Normal involutional change following pregnancy.

Pathology: Large pale cells surrounding vessels in endometrium and myometrium. Sometimes thrombosis, calcification, and hemosiderin are present.

Bronson R, et al. Involution of placental site and corpus luteum in the monkey. Am J Obstet & Gynecol 113:70-75, 1972.

Etiology: Associated with calcium pyrophosphate crystal deposition in joint.

Clinical: Enlarged joints, muscle contracture and wasting. Common in rhesus.

Pathology: Can affect any joint. Interphalangeal joints and knees most obviously affected. Reduced synovial fluid, cartilage erosion and ulceration, synovial hyperplasia, neutrophilic infiltrates. Calcium pyrophosphate crystals can be observed in articular surfaces by SEM in many cases. May be a form of CPDD (pseudogout).

Roberts ED, et al. Calcium pyrophosphate deposition disease (CPDD) in nonhuman primates. Am J Path 116:359-361, 1984.

Roberts ED, et al. Calcium pyrophosphate deposition in nonhuman primates. Vet Pathol 21:592-596, 1984.

Kandel RA, et al. Calcium pyrophosphate dihydrate crystal deposition disease with concurrent vertebral hyperostosis in a Barbary ape. Arth & Rheum 26:682-687, 1983.

Kessler MJ, et al. Reduction of passive extension and radiographic evidence of degenerative joint disease in caged and free-ranging aged rhesus monkeys (Macaca mulatta). J Med Primatol 15:1-9, 1986.

Renlund RC, et al. Rhesus monkeys as a model for calcium pyrophosphate dihydrate crystal deposition disease. J Med Primatol 15:11-16, 1986.

Roberts ED. Pyrophosphate arthropathy, Macaca mulatta. In: Jones TC, et al. (eds). Monographs on pathology of laboratory animals: Nonhuman primates II. Springer-Verlag, 1993, 138-142.

Etiology: High environmental temperature, insufficient fluids, exertion (often follows fighting). Conditioning is important - don't move animals from air conditioned quarters to outside quarters in extreme heat.

Clinical: Markedly elevated temperature, disorientation, dehydration, coma.

Pathology: Tissues often appear autolyzed out of proportion to time after death. Petechial hemorrhages on serosal surfaces, congested lungs, muscles appear "boiled". Histologically there is often extensive rhabdomyolysis.

Etiology: Low environmental temperature. Often follows heating system failures. Susceptibility varies with species.

Clinical: Low body temperature. Subcutaneous edema, muscular stiffness, feeble movements. Necrosis of extremities if frostbite occurs. Animals housed alone in metal cages particularly susceptible.

Pathology: None specific for hypothermia. Necrosis of extremities, especially tail, in frostbite.

Laber-Laird K, et al. Unexpected frostbite in Cynomolgus macaques after a short exposure to snow. Lab Anim Sci 38:325-326, 1988.

Etiology: Fight injuries in group housed animals, particularly in breeding season or when new animals are added to group. Esp. common in rhesus. Important to remember that rhesus monkeys are captive wild animals with a complex social structure which can be successfully dealt with only according to their own rules.

Clinical: Lacerations, bruises, abrasions, punctures, crush injuries of face and distal extremities. Injuries to underlying soft tissue are often more extensive than is apparent from the appearance of the skin lesions. Gangrene of distal extremities can develop due to extensive crushing and bacterial contamination.

Pathology: Extensive muscle necrosis, gangrene, myoglobinuric nephrosis, hyperkalemia.

Etiology: Injury occurs when a mother jumps to the floor while carrying an infant on her chest.

Clinical: Usually fatal. Healed fractures are seldom observed.

Pathology: Skull fractures with subdural, parenchymal, and ventricular hemorrhage.

Lee KJ, et al. Skull fractures in infant squirrel monkeys (Saimiri sciureus). Lab Anim Sci 30:1006-1008, 1980.

Etiology: Deficiency of Vitamin C in diet.

Clinical: Cephalohematomas in squirrel monkeys, epiphyseal fractures in rhesus monkeys. Anemia. Vitamin C deficiency is a problem only in guinea pigs and primates. Affected animals respond rapidly to Vitamin C (7.5-10 mg/Kg).

References:

De Klerk WA, et al. Vitamin C requirements of the vervet monkey (Cercopithecus aethiops) under experimental conditions. S African Med J 47:705-708, 1973.

Demaray SY, et al. Suspected ascorbic acid deficiency in a colony of squirrel monkeys (Saimiri sciureus). Lab Anim Sci 28:457-460, 1978.

Blackwell CA, et al. Cranial hyperostosis of squirrel monkeys (Saimiri sciureus). Lab Anim Sci 24:541-544, 1974.

Ratterree MS, et al. Vitamin C deficiency in captive nonhuman primates fed commercial primate diet. Lab Anim Sci 40:165-168, 1990.

Eisele PH, et al. Skeletal lesions and anemia associated with ascorbic acid deficiency in juvenile rhesus macaques. Lab Anim Sci 42:245-249, 1992.

Roberts ED. Vitamin C deficiency, old and new world monkeys. Monographs on Pathology of Laboratory Animals: Nonhuman Primates I, Springer-Verlag, 1993, 202-206.

Borda JT, et al. Ascorbic acid deficiency in Cebus apella. Lab Primate Newsletter 35:5-6, 1996.

Etiology: Torsions, terminal starvation.

Clinical: None.

Pathology: Firm yellow nodules in mesenteric fat. Histologically these consist of granulomatous fat necrosis and mineralization. Incidental finding, especially in rhesus. Saponification consists of innumerable pinpoint white spots in the subcutaneous and visceral fat and is a terminal event. The lesions are due to soap formation and are not associated with inflammation.

Etiology: Anorexia and acute weight loss from any cause in obese monkeys.

Clinical: Occurs in obese macaques. Anorexia, lethargy, sudden death. Azotemia.

Pathology: Affected animals are usually still fat, even though there has been recent weight loss. Fatty change in liver and kidney, small foci of necrosis and areas of ectatic acinii in pancreas. Exact mechanism unknown.

Bronson RT, et al. Fatal fasting syndrome of obese macaques. Lab Anim Sci 32:187-192, 1982.

Laber-Laird KE, et al. Fatal fatty liver-kidney syndrome in obese monkeys. Lab Anim Sci 37:205-209, 1987.

Gliatto JM, et al. Fatal fasting syndrome of obese macaques. Monographs on Pathology of Laboratory Animals: Nonhuman Primates I, Springer-Verlag, 1993, 198-202.

Etiology: Diet deficient in vitamin D3. Ca/P imbalance from feeding excessive fruit may also contribute.

Clinical: NWM (cannot utilize vitamin D2). Distorted limbs, kyphosis, pathologic fractures, decreased bone radiodensity. Should be a disease of the past but may occasionally see in pet monkeys.

Pathology: Simian bone disease is a nutritional secondary hyperparathyroidism which results in bone resorption and fibrous replacement.

Hunt RD, et al. A comparison of vitamin D2 and D3 in new world primates I. Production and regression of osteodystrophia fibrosa. Lab Anim Care 17:222-234, 1967.

Duboulay GH, et al. Nutritional bone disease in captive primates. Symp Zool Soc London 21:223, 1968.

Krook L, et al. Simian bone disease - a secondary hyperparathyroidism. Cornell Vet 52:459, 1962.

Etiology: Unknown. Responds to parenteral Vit E & Se, even though diet and serum levels seem adequate. Some of the 11 distinct karyotypes are susceptible, while others are not. Enteropathy and colitis may cause malabsorption of vitamin E.

Clinical: Hemolytic anemia.

Pathology: Pallor of mucus membranes and other tissues, icterus, petechiae in CNS. Anemia, circulating nucleated RBC's, centrilobular necrosis in liver, EMH in liver and spleen, hemosiderosis, microinfarcts in brain, edema, ascites, icterus, pulmonary edema, cardiomegaly, muscle necrosis.

Sehgal RC, et al. Therapeutic efficacy of vitamin E & Selenium in treating hemolytic anemia of owl monkeys. Lab Anim Sci 30:92-98, 1980.

Bronson RT, et al. Morphology and morphogenesis of cerebral ring hemorrhages in anemic monkeys. Acta Neuropathol 51:155-160, 1980.

Bronson RT. Necrotizing myopathy associated with hemolytic anemia in owl monkeys. J Neurological Sci 47:105-109, 1980.

King NW. Vitamin E-responsive hemolytic anemia and necrotizing myopathy, owl monkeys. In: Jones TC, et al. (eds). Monographs on pathology of laboratory animals: Nonhuman primates II. Springer-Verlag, 1993, 226-232.

Etiology: Unknown. Possibly immune reaction to bacterial lipopolysaccharides.

Transmission: Unknown

Clinical: Chronic nonresponsive watery diarrhea, wasting, joint contracture with or without arthritis. Fecal cultures and parasitic exams negative. Appetite remains good.

Pathology: Diffuse lymphoplasmacytic colitis. Often associated with amyloidosis and arthritis.

Etiology: Hepatocystis kochi, H. simiae (African) & H. taiwanensis, H. semnopitheci (Asian).

Transmission: Midge (culicoides).

Clinical: None. African and Asian monkeys.

Pathology: 2-4 mm opaque cysts in liver. These rupture to release merozoites which infect RBC's. Trophozoites occur in RBC's. Schizogeny occurs in liver, so there are no malarial symptoms. Heavy parasitemia can alter hematology because infected RBC's do not lyse and Coulter counters therefore count them as nucleated cells. Ruptured cysts result in eosinophilic granulomas which resolve into small circular scars in the liver.

References:

Turner TR, et al. Hepatocystis parasitemia in wild Kenya vervet monkeys. J Med Primatol 11:19 1-194, 1982.

Leathers CW. The prevalence of Hepatocystis kochi in African green monkeys. Lab Anim Sci 28:186-189, 1978.

Vickers J. Hepatocystis kochi in Cercopithecus monkeys. JAVMA 149:906-908, 1966.

Nakazawa M, et al. Histopathology of Hepatocystosis in Cynomolgus monkeys imported from southeast Asia. Jap J Med Sci 49:295-301, 1987.

Ryan MJ, et al. Diagnostic exercise: hepatic granulomas in a Cynomolgus monkey. Lab Anim Sci 36:56-58, 1986.

Etiology: Plasmodium cynomolgi, P. inui, P. knowlesi, P. gonderi, P. brasilianum, and numerous others.

Transmission: Mosquito.

Clinical: OWM, NWM, apes. Usually subclinical unless splenectomized or immunosuppressed. Some species will cause disease in monkeys characterized by jaundice, anorexia, listlessness, fever, anemia, splenomegaly. Periodic release of organisms from RBC's causes clinical signs. The length of the cycle is determined by the periodicity of the particular species. Mixed infections are common.

Pathology: Grossly, the lungs, liver, and spleen are gray and the blood thin. Histologically, tissue macrophages are filled with malarial pigment, and there are hemodsiderosis and parasitized RBC's. Intravascular clotting with thrombi and parasitized RBC's is common. Often there is pulmonary and cerebral edema.

Bray R. The malaria parasites of anthropoid apes. J Parasitol 49:888-891, 1963.

Eyles DE. The species of simian malaria: taxonomy, morphology, life cycle, and geographical distribution of the monkey species. J Parasitol 49:866-887, 1963.

Stokes WS, et al. Acute clinical malaria in a cynomolgus monkey. Lab Anim Sci 33:81-85, 1983.

Donovan JD, et al. Hematologic characterization of naturally occurring malaria in Cynomolgus monkeys. Lab Anim Sci 33:86-89, 1983.

McWilson W. Simian and anthropoid malarias - their role in human disease. Lab Anim Care 20:368-376, 1970.

Young MD. Natural and induced malarias in western hemisphere monkeys. Lab Anim Care 20:361-367, 1970.

Schofield LD, et al. An outbreak of Plasmodium inui malaria in a colony of diabetic rhesus monkeys. Lab Anim Sci 35:167-168, 1985.

Schmidt LH, et al. The characteristics of Plasmodium cynomolgi infections in various old world primates. Am J Trop Med Hyg 26:356-372, 1977.

Whiteley HE, et al. Pathologic changes associated with fatal Plasmodium falciparum infection in the Bolivian squirrel monkey. Am J Trop Med Hyg 37:1-8, 1987.

Ibiwoye MO, et al. Cerebral malaria in the rhesus monkey (Macaca mulatta): Light and electron microscopic changes in blood cells and cerebrovascular endothelia. Comp Haematol Int 3:153-158, 1993.

Fooden J. Malaria in macaques. Int J Primatol 15:573-596, 1994.

Etiology: Entamoeba histolytica, Balamuthia mandrillaris.

Transmission: Oral

Clinical: Asymptomatic carriers are common, but amoebae can cause diarrhea. OWM, NWM, apes.

Pathology: Often find amoebae in mucosa without associated lesions or clinical signs. Can cause mild to severe colitis. Can have chronic low grade colitis or classical flask-shaped ulcers. Trophozoites are seen in the mucosa, submucosa, and sometimes the muscularis. Trophozoites sometimes invade lymphatics or blood vessels and spread to form amoebic abscesses in the lung, liver, or brain. In leaf eating monkeys (ie, Colobus), the stomach is the primary site of infection, and organisms may not be found in the feces.

Balamuthia mandrillaris, a free-living amoeba, has caused fatal meningeoencephalitis in nonhuman primates.

Bond PB, et al. Pathologic study of natural amebic infection in macaques. Am J Trop Med 26:625-629, 1946.

Johnson CM. Observations on natural infections of Entamoeba histolytica in Ateles and rhesus monkeys. Am J Trop Med 21:49-61, 1941.

Beaver PC, et al. Invasive amebiasis in naturally infected new world and old world monkeys with and without clinical disease. Am J Trop Med Hyg 39:343-352, 1988.

Loomis MR, et al. Hepatic and gastric amebiasis in black and white Colobus monkeys. JAVMA 183:1188-1191, 1983.

Palmieri JR., et al. Gastric amebiasis in a silvered leaf monkey. JAVMA 185:1374-1375, 1984.

Amyx HL, et al. Hepatic amebiasis in spider monkeys. Am J Trop Med Hyg 27:888-891, 1978

Rideout BA, et al. Fatal infections with Balamuthia mandrillaris (a free-living amoeba) in gorillas and other old world primates. Vet Pathol 34:15-22, 1997.

Etiology: Balantidium coli.

Transmission: Oral.

Clinical: OWM, NWM, apes. Questionable pathogenicity. Usually asymptomatic, but sometimes associated with diarrhea, especially in apes. Thought to be a secondary invader only.

Pathology: Organisms are often found in the lumen of the colon of normal animals and in ulcerative lesions, mucosa, capillaries, lymphatics, and mesenteric lymph nodes of animals with colitis. Usually associated with some other pathogen. May be a primary pathogen in great apes.

Lockborn TA. Balantidium infection associated with diarrhea in primates. Trans Roy Soc Trop Med Hyg 42:291-293, 1948.

Kim JCS, et al. Balantidiasis in a chimpanzee. Lab Anim Sci 12:231-233, 1978.

Teare JA, et al. Balantidiasis (epizootic) in gorillas. JAVMA 181:1345-1347, 1982.

Lee RV, et al. Typhlitis due to Balantidium coli in captive lowland gorillas. Rev Inf Dis 12:1052-1059, 1990.

Etiology: Encephalitozoon cuniculi

Transmission: Oral, transplacental. Organisms shed in urine.

Clinical: NWM. Usually none, but may be associated with stillbirths and abortions in squirrel monkeys.

Pathology: Focal microgranulomas in brain, kidney, lung, adrenal, liver, placenta. Vasculitis and aortitis common. Gram-positive organisms in cysts and in lesions.

Brown RJ, et al. Nosematosis in a squirrel monkey. Naval Aerospace Medical Research Laboratory Special Report 72-1, 1972.

Anver MR, et al. Congenital encephalitozoonosis in a squirrel monkey. Vet Pathol (:475-480, 1972.

Zeman DH, et al. Encephalitozoonosis in squirrel monkeys. Vet Pathol 22:24-31, 1985.

Shadduck JA, et al. Serologic evidence of Encephalitozoon cuniculi infection in a colony of squirrel monkeys (Saimiri sciureus). Lab Anim Sci 39:328-30, 1989.

Baskin GB. Encephalitozoon cuniculi infection, squirrel monkey. In: Jones TC, et al. (eds). Monographs on pathology of laboratory animals: Nonhuman primates II. Springer-Verlag, 1993, 193-196.

Etiology: Enterocytozoon bieneusi

Transmission: unknown. Organisms are ubiquitous in nature.

Clinical: Carried asymptomatically in hepatobiliary tree of normal rhesus monkeys. Infected animals may have elevated alkaline phosphatase. Occurs as an opportunistic infection in SIV-infected macaques. Clinical signs specific for this organism have not been reported, but has been associated with chronic diarrhea.

Mansfield KG, et al. Identification of an Enterocytozoon bieneusi-like microsporidian parasite in simian-immunodeficiency-virus-inoculated macaques with hepatobiliary disease. Am J Pathol 150:1395-1405, 1997.

Carville A, et al. Development and application of genetic probes for detection of Enterocytozoon bieneusi in formalin-fixed stools and in intestinal biopsy specimens from infected patients.

Chalifoux LV, et al. Ultrastructural morphology of Enterocytozoon bieneusi in biliary epithelium of rhesus macaques (Macaca mulatta). Vet Pathol 35:292-296, 1998.

Mansfield KG, et al. Localization of persistent Enterocytozoon bieneusi infection in normal rhesus macaques (Macaca mulatta) to the hepatobiliary tree. J Clin Microbiol 36:2336-2338, 1998.

Etiology: Sarcocystis sp.

Transmission: Fecal-oral. Primate is intermediate host. Final host is a carnivore.

Clinical: None. Infects many species of wild-caught monkeys.

Pathology: Presence of cyst in skeletal muscle. No inflammatory reaction usually. Rarely, eosinophilic myositis.

Kuncl RW, et al. Prevalence and ultrastructure of Sarcocystis in rhesus monkeys. Jpn J Vet Sci 50:519-527, 1988.

Dubin IN, et al. Sarcocystis in Macaca mulatta. J Parasitol 33:515-553, 1947.

Karr SL, et al. A survey of sarcocystis in nonhuman primates. Lab Anim Sci 25:641-645, 1975.

Terrell TG, et al. Chronic eosinophilic myositis in a rhesus monkey infected with sarcosporidiosis. Vet Pathol 9:266-271, 1972.

Mandour AM. Sarcocystis nesbitti n. sp. from the rhesus monkey. J Protozool 16:353-354, 1969.

Etiology: Cryptosporidium sp.

Transmission: Fecal-oral.

Clinical: Diarrhea, weight loss, anorexia. Clinical disease occurs in young, debilitated, or immunosuppressed animals. Will resolve spontaneously in normal animals, untreatable in immunodeficient animals. Cryptosporidium is a common opportunistic infection in SRV and SIV-infected macaques.

Pathology: Organisms present on surface epithelium of intestinal villi, villus atrophy, eosinophilic inflammation in lamina propria. In immunodeficient monkeys, can see generalized infection with organisms and eosinophilic inflammation in conjunctiva, trachea, bronchioles, bile ducts and gallbladder, and pancreatic duct. There is often marked hyperplasia of biliary and pancreatic duct epithelium and periductal fibrosis.

Miller RA, et al. Clinical and parasitologic aspects of cryptosporidiosis in nonhuman primates. Lab Anim Sci 40:42-46, 1990.

Blanchard JL, et al. Disseminated cryptosporidiosis in Simian Immunodeficiency Virus/Delta-infected rhesus monkeys. Vet Pathol 24:454-456, 1987.

Wilson DW, et al. Diarrhea associated with Cryptosporidium spp in juvenile macaques. Vet Pathol 21:447-450, 1984.

Kovatch RM, et al. Cryptosporidiosis in two juvenile rhesus monkeys. Vet Pathol 9:426-440, 1972.

Miller RA, et al. Experimental cryptosporidiosis in a primate model. J Inf Dis 161:312-315, 1990.

Lackner AA, et al. Cryptosporidiosis, intestines, pancreatic duct, bile duct, gallbladder, Macaca mulatta. In: Jones TC, et al. (eds). Monographs on pathology of laboratory animals: Nonhuman primates II. Springer-Verlag, 1993, 41-46.

Baskin GB. Cryptosporidiosis of the conjunctiva in SIV-infected rhesus monkeys. J Parasitol 82:630-632,1996.

Etiology: Trichomonas spp.

Transmission: fecal-oral

Clinical: Usually none. Widespread asymptomatic enteric infection. Numbers often increase in diarrhea, but relationship to clinical signs not demonstrated.

Pathology: Often fill crypts in large intestine. May invade epithelium without inflammatory reaction. Occasional invasion of stomach and colon with inflammation reported. Trichomonal gastritis occurs in SIV-infected rhesus monkeys.

Migaki G, et al. Trichomonal granuloma of the pelvic cavity in a rhesus monkey. Vet Pathol 15:679-681, 1978.

Bunton TE, et al. Invasive trichomoniasis in a Callicebus moloch. Vet Pathol 20:491-494, 1983.

Pindak FF, et al. Detection and cultivation of intestinal trichomonads of squirrel monkeys (Saimiri sciureus). Am J Primatol 9:197-205, 1985.

Scimeca JM, et al. Intestinal trichomonads (Tritrichomonas mobilensis) in the natural host Saimiri sciureus and Saimiri boliviensis. Vet Pathol 26:144-147, 1989.

Blanchard JL, et al. Trichomonas gastritis in rhesus monkeys infected with the Simian Immunodeficiency Virus. J Inf Dis 157:1092-1093, 1988.

Brady AG, et al. Enteric trichomonads of squirrel monkeys (Saimiri sp.): natural infestation and treatment. Am J Primatol 14:65-71, 1988.

Blanchard JL. Trichomonas gastritis. In: Jones TC, et al. (eds). Monographs on pathology of laboratory animals: Nonhuman primates II. Springer-Verlag, 1993, 38-40.

Brack M, et al. Intestinal trichomoniasis due to Tritrichomonas mobilensis in tree shrews (Tupaia belangeri). Lab Anim Sci 45:533-537, 1995.

Etiology: Giardia lamblia

Transmission: fecal-oral

Clinical: Asymptomatic carriers are common. May be associated with self-limiting diarrhea and malabsorption. Can be a serious opportunistic infection in SIV-infected macaques.

Pathology: Presence of organisms on epithelial surface of small intestine. Organisms most common in middle of jejunum. Mucosa may be normal or have nonspecific villus atrophy and inflammation of lamina propria.

Hamlen HJ, et al. Giardiasis in laboratory-housed squirrel monkeys: A retrospective study. Lab Anim Sci 44:235-239, 1994.

Etiology: Trypanosoma cruzi

Transmission: Insect vector (Triatoma, reduviid"kissing bug"). Reservoir in many mammals.

Clinical: Can be asymptomatic, or lymphadenopathy, hepatosplenomegaly, heart failure, eyelid edema, drowsiness (sleeping sickness-like), sudden death.

Pathology: Enlarged mottled heart. Chronic myocarditis with cystic collections of leishmanial forms in muscle cells. Skeletal and smooth muscle can be affected. Necrosis and glial nodules in brain. Trypanosomal forms in blood.

Olson LC, et al. Encephalitis associated with Trypanosoma cruzi in a celebes black macaque. Lab Anim Sci 36:667-670.

Seibold HR, et al. American trypanosomiasis (Chagas' disease) in Hylobates pileatus. Lab Anim Care 20:514-517, 1970.

Marinkelle CJ. The prevalence of Trypanosoma cruzi infection in Columbian monkeys and marmosets. Ann Trop Med Parasitol 76:121-124, 1982.

Kasa TJ, et al. An endemic focus of Trypanosoma cruzi infection in a subhuman primate research colony. J Am Vet Med Assn 171:850-854, 1977.

Gleiser CA, et al. Trypanosoma cruzi infection in a colony-born baboon. J Am Vet Med Assn 189:1225-1226, 1986.

Etiology: Toxoplasma gondii

Transmission: Ingestion of food contaminated by cat feces containing oocysts or ingestion of raw meat containing cysts. Remember that many NHP will catch and eat rodents. Primates in the wild are rarely seropositive. Epizootics have occurred in captive New World species.

Clinical: NWM more susceptible than OWM. Usually asymptomatic in OWM. Lethargy, CNS signs, sudden death.

Pathology: Pulmonary edema, lymphadenopathy, splenomegaly, intestinal ulceration. Necrosis with or without inflammation in liver, spleen, lymph nodes, heart, lung, adrenal, intestinal muscle, brain. Individual organisms and cysts in tissues.

McKissick GE, et al. Enzootic toxoplasmosis in caged squirrel monkeys Saimiri sciureus. Path Vet 5:538-560, 1968.

Wong MM, et al. Spontaneous toxoplasmosis in macaques: a report of four cases. Lab Anim Sci 24:273-278, 1974.

McConnell EE, et al. Toxoplasmosis in free-ranging chacma baboons (Papio ursinus) from the Kruger national park. Trans Roy Soc Trop Med Hyg 67:851-855, 1973.

Hessler JR, et al. Lethal toxoplasmosis in a wooly monkey. J Am Vet Med Assn 159:1588-1594, 1971.

Dubey JP, et al. Acute death associated with Toxoplasma gondii in ring-tailed lemurs. J Am Vet Med Assn 187:1272-1273, 1985.

Dickson J, et al. Epidemic toxoplasmosis in captive squirrel monkeys (Saimiri sciureus). Vet Rec 112:302, 1983.

Schoondermark-Van de Ven E, et al. Congenital toxoplasmosis: An experimental study in rhesus monkeys for transmission and prenatal diagnosis. Exp Parasitol 77:200-211, 1993.

Anderson DC, et al. Toxoplasmosis. In: Jones TC, et al. (eds) Monographs on Pathology of Laboratory Animals: Nonhuman Primates I, Springer-Verlag, 1993, 63-70.

Etiology: Several species of biting and sucking lice described.

Clinical: Usually seen on debilitated animals caged alone. Do not seem to cause much damage.

Pathology: Presence of lice and eggs in hair.

Winsatt JH, et al. An infestation of sucking lice in a juvenile rhesus macaque. Lab Anim Sci 38:203, 1988.

Mader DR, et al. Management of an infestation of sucking lice in a colony of rhesus macaques. Lab Anim Sci 39:252-255, 1989.

Etiology: Pneumonyssus and Pneumonyssoides in the lungs; Rhinophaga in the nasal cavity.

Transmission: Unknown, but close contact required.

Clinical: Pneumonyssus simicola is the most important with nearly 100% incidence in rhesus monkeys. Usually there are no clinical signs. Radiographs are of little use in diagnosis. Lung mites can cause serious clinical disease in langurs and proboscis monkeys.

Pathology: Focal, yellow, 1-10 mm in diameter air filled cysts throughout the pulmonary parenchyma. The cysts are raised if they occur on the pleural surface. In severe cases, delicate fibrous adhesions develop between the visceral and parietal pleura. Bronchial lymph nodes are deeply pigmented due to deposition of mite pigment. Microscopic lesions consist of chronic bronchiolitis with bronchiectasis and eosinophilic granulomatous inflammation, cross sections of mites, and golden brown refractile pigment.

Innes JRM, et al. Pulmonary acariasis as an enzootic disease caused by Pneumonyssus simicola in imported monkeys. Am J Pathol 30:813-827, 1954.

Hull WB. Respiratory mite parasites in nonhuman primates. Lab Anim Care 20:402-406, 1970.

Brack M. Histochemistry of the lung mite pigment in infections of Pneumonyssus sp. in nonhuman primates. Parasitol 64:47-52, 1972.

Robinson PT, et al. Clinical and pathologic aspects of pulmonary acariasis in Duoc langur and Proboscis monkeys. Zool Garten 51:161-169, 1981.

Rawlings CA, et al. Pneumothorax associated with lung mite lesions in a rhesus monkey. Lab Anim Sci 23:259-261, 1973.

Joseph BE, et al. Treatment of pulmonary acariasis in rhesus macaques with ivermectin. Lab Anim Sci 34:360-364, 1984.

Etiology: Sarcoptes sp, Demodex sp, Psorergates sp.

Transmission: Contact.

Clinical: Sarcoptes and Demodex lesions in monkeys are similar to those in other animals. Psorergates causes focal non-pruritic plaques.

Pathology: Chronic dermatitis with cross-sections of mites in characteristic location for species.

Lebel RR, et al. Demodectic mites of subhuman primates. J Parasitol 59:719-722, 1973.

Lee KJ, et al. Psorergatic mange of the stumptail macaque. Lab Anim Sci 31:77-79, 1981.

Bowman TA, et al. Comparison of treatments for Psorergates mites in stumptailed macaques. Lab Anim Sci 37:100-102, 1987.

Goldman L, et al. Human infestation with scabies of monkeys. Arch Dermatol Syph 59:175-178, 1949.

Raulston GL. Psorergatic mites in Patas monkeys. Lab Anim Sci 22:107-108, 1972.

Hickey TE, et al. Demodectic mange in a Tamarin (Saguinus geoffroyi). Lab Anim Sci 33:192-193, 1983.

Seier JV. Psorergatic acariasis in vervet monkeys. Lab Anim 19:236-239, 1985.

Baskin GB. Cutaneous acariasis. In: Jones TC, et al. (eds) Monographs on Pathology of Laboratory Animals: Nonhuman Primates II, Springer-Verlag, 1993, 23-26.

Etiology: Armillifer & Porocephalus in OWM, Porocephalus in NWM.

Transmission: Oral. Monkeys are intermediate hosts. Final host is a primate-eating snake, where the adult form is found in the lung.

Clinical: None.

Pathology: Nymphs are found encysted in the pleural or peritoneal cavity. Nymphs are C-shaped, annulated, enclosed in a transparent cyst. There is no host reaction while the nymph is alive, but chronic inflammation if it dies.

Cosgrove GE, et al. The pathology of Pentastomid infection in primates. Lab Anim Care 20:354-360, 1970.

Lok JB, et al. Pentastomiasis in captive monkeys. Lab Anim Sci 37:496-496, 1987.

Etiology: Adult Cestodes: Cyclophyllidean tapeworms of the Families Anaplocephalidae (esp. Bertiella), Davaineidae, Hymenolepiididae, and Dilepididae are found in the intestine.

Larval Cestodes: Pseudophyllidean cestodes in the Family Diphyllobothriidae which form spargana (plerocercoid larvae), and Cyclophyllidean cestodes which form cysticercoid larvae, cysticercus larvae (Taenia), coenurus larvae (Multicepts), or hydatid larvae (Echinococcus) are found in various tissues.

Transmission: Ingestion of eggs or infected intermediate host (often arthropod).

Clinical: Usually none.

Pathology: Larvae are more commonly found than adults in nonhuman primates. Larvae may be found in retroperitoneal, subcutaneous, or muscular tissues or in the abdominal, pleural, or cranial cavities. There is usually little host response. Diagnose by characteristic morphology of the larvae.

Guillot LM, et al. Pulmonary cestodiasis in a cynomolgus monkey (Macaca fascicularis). Lab Anim Sci 42:158-160, 1992.

Houser WD, et al. Hydatid disease in a macaque. J Am Vet Med Assn 159:1574-1577, 1971.

Hubbard GB, et al. Mesocestoides infection in captive olive baboons (Papio cynocephalus anubis). Lab Anim Sci 43:625-627, 1993.

Fincham JE, et al. Pleural Mesocestoides and cardiac shock in an obese vervet monkey (Cercopithecus aethiops). Vet Pathol 32:330-333, 1995.

Sasseville VG, et al. A case of pulmonary cestodiasis in a simian immunodeficiency virus-infected pigtailed macaque (Macaca nemestrina) in which virus-infected leukocytes are present within the lesion. J Med Primatol 25:251-256, 1996.

Etiology: Filaroides sp, Filariopsis sp.

Transmission: Larvae are passed in feces, the rest of the cycle is unknown.

Clinical: None. Most common in NWM.

Pathology: 1-2mm focal brown irregular spot on the pleural surface of the lung. The small slender adults are found in terminal bronchioles and alveoli. The females are viviparous. There is usually little inflammation.

Etiology: Dipetalonema sp. Tetrapetalonema sp, Wuchereria sp, and Edesonfilaria sp. are most common, but there are over 40 species.

Transmission: Blood sucking insects - midge, mosquito.

Clinical: None. Found in NWM & OWM, but most common in NWM.

Pathology: The long slender adults are found in the peritoneal cavity (Dipetalonema sp.), subcutis, or connective tissue depending on species. In heavy peritoneal infections there may be a slight increase in peritoneal fluid and slight villous proliferation of the serosa, or proliferation of fibrous connective tissue. Microfilaria are found circulating in the blood and can be identified by the pattern of acid phophatase staining. Granulomas and arterial thickening in the spleen are associated with microfilaria, esp. of Edesonfilaria, in cynomolgus monkeys.

Dunn F, et al. On some filarial parasites of South American primates with a description of Tetrapetalonema tamarinae from the Peruvian tamarin marmoset. J Helminthol 37:261-286, 1963.

Jacotot H, et al. Splenite chronique dans un cas de filariose chez un cynocephale. Bull Soc Pathol Exot 49:300-301, 1956.

McCoy OR. Filarial parasites of the monkeys of Panama. Am J Trop Med Hyg 16:383-403, 1936.

Webber WAF. The filarial parasites of primates: A review. I: Dirofilaria and Dipetalonema. Ann Trop Med Parasitol 49:123-141, 1955.

Narama I, et al. Microfilarial granulomas in the spleens of wild-caught Cynomolgus monkeys. Vet Pathol 22:355-362, 1985.

Nonoyama T, et al. A pathological study in cynomolgus monkeys infected with Edesonfilaria malayensis. Lab Anim Sci 34:604-609, 1984.

Eberhard ML. Chemotherapy of filariasis in squirrel monkeys. Lab Anim Sci 32:397-400, 1982.

Chalifoux LV. Filariasis, New World primates. In: Jones TC, et al. (eds) Monographs on Pathology of Laboratory Animals: Nonhuman Primates I, Springer-Verlag, 1993, 206-214.

Etiology: Strongyloides cebus in NWM, S. fulleborni in OWM.

Transmission: Oral, skin penetration. Complex life cycle.

Clinical: Asymptomatic to severe diarrhea, coughing.

Pathology: Ulcerative, hemorrhagic enterocolitis, pulmonary hemorrhage. Adult females (only the females are parasitic) burrow into the mucosa of the proximal small intestine, forming tunnels in which ova are deposited. Larvae hatch and break out of the tunnels into the lumen. In hyperinfection, lst stage larvae develop rapidly to 3rd stage and penetrate bowel before being passed out in the feces. This process may affect the full thickness of colon and sometimes the ileum. There is sometimes a severe inflammatory response to the larvae. May see larvae in lymphatics. Hemorrhage in lung is due to migrating larvae. In autoinfection, 3rd stage larvae pass out through the anus and penetrate the perianal skin. Strongyloidiasis may be particularly severe in apes.

Depaoli A, et al. Fatal strongyloidiasis in gibbons. Vet Pathol 15:31-39, 1978.

Harper JS, et al. Disseminated strongyloidiasis in Erythrocebus patas. Am J Primatol 3:89-98, 1982.

Leeflang PD, et al. Strongyloidiasis in Orangutans at Perth Zoo; an apparently successful eradication programme. Int Zoo Yb 24/25:256-260, 1986.

Etiology: Nochtia nochti

Transmission: Oral. Direct life cycle. Affects Asian macaques.

Clinical: None

Pathology: Gastric polyps or papillomas, which contain the embedded slender bright red parasite and eggs, at junction of fundic and pyloric regions of stomach. Severe hyperplasia of mucus neck cells of gastric crypts and mucous metaplasia of underlying fundic or pyloric glands. Lesions do not become malignant. Physaloptera tumefaciens can produce a similar lesion, but is much larger and only the head is buried in the mucosa, with the body free in the gastric lumen.

Bonne C, et al. On the production of gastric tumors bordering on malignancy in Japanese monkeys through the agency of Nochtia nochti, a parasitic nematode. Am J Cancer 37:173-185, 1939.

Smetana HF, et al. Gastric papillomata in Macaca speciosa induced by Nochtia nochti. J Parasitol 55:349-351, 1969.

King NW. Nochtiasis. In: Jones TC, et al. (eds). Monographs on pathology of laboratory animals: Nonhuman primates II. Springer-Verlag, 1993, 238-240.

Etiology: Anatrichosoma cutaneum, A. cynomolgi.

Transmission: Unknown. Embryonated eggs deposited in nasal or cutaneous stratified squamous epithelium and sloughed.

Clinical: OWM. In nasal epithelium, none. In skin, mild peeling of epidermis of palms and soles. May see serpentine tracts with intense inflammation.

Pathology: Cross-sections of worms and eggs in nasal epithelium or skin of face, hands, feet. Usually little inflammation. Seldom see in animals routinely treated with anthelminthics.

References:

Long GG, et al. Anatrichosoma cynomolgi in rhesus monkeys. J Parasitol 62: 111-115, 1976.

Kessler MJ. Nasal and cutaneous anatrichosomiasis in the free-ranging rhesus monkeys of Cayo Santiago. Am J Primatol 3:55-60, 1982.

Ulrich CP, et. at. An epidemiological survey of wild caught and domestic born rhesus monkeys for Anatrichosoma. Lab Anim Sci 31:726-727, 1981.

OESOPHAGOSTOMUM (nodular worms)

Etiology: Several species of Oesophagostomum, not clearly defined.

Transmission: Oral. Direct life cycle.

Clinical: OWM. Usually asymptomatic. Heavy infections are associated with diarrhea and anemia.

Pathology: Adults live free in the lumen of the large intestine and cause no damage. Ingested larvae develop into 4th stage in the gut wall and then return to the lumen. Larvae cause the characteristic lesion which consists of 3-4 mm dark nodules in the submucosa and muscularis of the large intestine. Nodules contain brown exudate and small white larvae. Histologically the nodules consist of a central abscess with necrosis and mixed inflammatory cells encircled by fibrosis. Nodules sometimes occur in ectopic sites such as the peritoneum, kidney, liver, lung, etc.

Chang J, et al. Disseminated oesophogostomiasis in the rhesus monkey. JAVMA 167:628-630, 1975.

TRICHURIS (whipworms)

Etiology: Trichuris trichiura.

Transmission: Oral. Direct life cycle.

Clinical: OWM and NWM. Usually asymptomatic.

Pathology: Adults found with anterior end embedded in mucosa of cecum and proximal colon. Little host reaction. Heavy infestations rarely associated with intussusception.

Etiology: Physaloptera tumefaciens, P. dilatata.

Transmission: Ingestion of intermediate host (cockroach).

Clinical: Usually none.

Pathology: Adults attached to gastric mucosa. Adults resemble ascarids, but are attached to mucosa.

ACANTHOCEPHALA (thorny-headed worms)

Etiology: Prosthenorchis elegans (cecum and colon), P. spirula (terminal ileum).

Transmission: Ingestion of intermediate host - cockroaches and beetles.

Clinical: NWM. Non-specific signs such as cachexia, intussusception, rectal prolapse.

Pathology: Adults attach to the intestinal mucosa causing marked granulomatous inflammation and a nodule visible from the serosal surface. They often penetrate the mucosa and invade the muscle layers. The attachment sites may perforate and cause peritonitis. Heavy infections can cause mechanical blockage.

Takos MJ, et al. The pathology and pathogenesis of fatal infection due to an acanthocephalid parasite of marmoset monkeys. Am J Trop Med Hyg 7:90-94, 1958.

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Etiology: Athesmia foxi

Transmission: Mollusk is intermediate host.

Clinical: Usually none. Common in NWM - capuchin, squirrel monkey, marmosets, titi monkeys.

Pathology: Presence of small trematodes in the interlobular bile ducts of NWM. Usually found on histopathology. Small size makes them easy to miss on gross.

Cosgrove GE, et al. Helminth parasites of the tamarin, Saquinus fuscicollis. Lab Anim Care 18:654-656, 1968.

Garner E, et al. Multiple helminth infections in cinnamon-ringtailed monkeys (Cebus albifrons). Lab Anim Care 17:310-315, 1967.

Etiology: Gastrodiscoides hominis

Transmission: Affects Macaca spp. and humans. Snail is intermediate host. Macaque becomes infected by ingesting metacercariae encysted on vegetation.

Clinical: Usually asymptomatic. Large numbers may cause mucoid diarrhea.

Pathology: Adults in lumen of cecum and colon.

Etiology: Schistosoma mansoni, S. hematobium, S. japonicum

Transmission: Snail is intermediate host.

Clinical: Usually none.

Pathology: Adults are in mesenteric (mansoni, japonicum) or pelvic and mesenteric (hematobium) veins of various OWM and NWM. Phlebitis and thrombosis can occur. Black pigment in liver and spleen. Granulomas containing eggs in many tissues, esp. liver. Eggs may also be in vessels. Eggs are identified by characteristic spine.

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Genetics Laboratory for typing Macaca mulatta: William H. Stone, Ph.D., Trinity University, San Antonio, TX 78284 (512-736-8347).

Simian Virus Reference Laboratory: Dr. S. S. Kalter, Virus Reference Laboratory, Suite 202-203, 7540 Louis Pasteur, San Antonio, TX 78229, (512-696-5510).

Herpes B serology and virology: NIH B Virus Resource Laboratory, Viral Immunology Center, Georgia State University, 50 Decatur Street, Atlanta, GA 30303. Information and submission forms can be obtained from Dr. Richard D. Henkel, NIH B Virus Reference Laboratory, Georgia State University, PO Box 4118, Atlanta, GA 30302-4118. (404-651-0808; biordh@panther.gsu.edu)

Primate Information Center: Mail Stop SJ-50, Regional Primate Research Center, University of Washington, Seattle, WA 98195, (206-543-4376).

Laboratory Primate Newsletter: Judith E. Schrier, Editor, Psychology Dept., Box 1853, Brown University, Providence, RI 20912.

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