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Pathology of Nonhuman Primates

Gary B. Baskin, DVM

Tulane Regional Primate Research Center

Tulane University

Covington, Louisiana

gbask@tpc.tulane.edu

BACTERIAL DISEASES

MYCOBACTERIOSIS

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.

References:

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.

LEPROSY

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.

References:

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.

SHIGELLOSIS

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.

References:

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.

SALMONELLA

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.

References:

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.

CAMPYLOBACTERIOSIS

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.

References:

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.

HELICOBACTERIOSIS

Etiology: Helicobacter pylori

Transmission: Oral

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

Pathology: Seldom grossly apparent, but sometimes focal reddening or erosions of gastric mucosa. Mononuclear inflammatory cell infiltrate in lamina propria of stomach, superficial erosions, epithelial hyperplasia. Can see organism with HE, but Giemsa or silver stains will more readily demonstrate slightly curved, rod-shaped, gull-wing, or loosely-coiled organisms, 1-4 µm long, associated with gastric epithelium in antral mucosa. Best to culture biopsy rather than swab, are urease positive. Can use rapid urease test rather than culture. Most common and severe in antrum.

References:

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.

Stadtländer CT, et al. Adaptation of the [¹³C]urea breath test as a noninvasive method for detection of Helicobacter pylori infection in squirrel monkeys (Saimiri spp.). Lab Anim Sci 45:239-243, 1995.

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.

GASTROSPIRILLUM HOMINIS-LIKE ORGANISMS (GHLO), H. HEILMANNII

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

Pathology: GHLO are nearly ubiquitous in rhesus monkeys, mainly in the fundus of the stomach. Organisms are 3.5-10 µm long, tightly coiled with 6-8 coils per cell, spiral bacteria with bipolar flagella in surface mucus, lumens of gastric pits, and in parietal cells.

References:

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.

STREPTOCOCCUS PNEUMONIAE (DIPLOCOCCUS)

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.

References:

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.

YERSINIOSIS

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.

References:

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.

LISTERIOSIS

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.

References:

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.

BORDETELLOSIS

Etiology: Bordetella bronchiseptica

Transmission: Respiratory

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

Pathology: Fibrinopurulent hemorrhagic bronchopneumonia. Fibroplasia around bronchioles.

References:

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.

BRANHAMELLA CATARRHALIS

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

TETANUS

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.

References:

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.

STAPHYLOCOCCUS

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.

KLEBSIELLA

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.

References:

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.

ESCHERICHIA COLI

Etiology: E. coli

Transmission: Fecal-oral

Clinical: Pneumonia, meningitis, diarrhea.

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

References:

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

PSEUDOMONAS spp.

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.

NOCARDIOSIS

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.

References:

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.

VIRAL DISEASES

HERPES B

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

Transmission: Bites, scratches, venereal, ocular, aerosol(?). 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 lifelong 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, gloves, and eye protection 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)

References:

Perkins FT, et al. Precautions against B virus infection. Brit Med J 1:899-901, 1966.

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.

Artenstein AW, et al. Human infection with B virus following a needlestick injury. Rev Infect Dis 13:288-291, 1991.

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.

CDC. Fatal Cercopithecine herpesvirus 1 (B virus) infection following a mucocutaneous exposure and interim recommendations for worker protection. Morbidity & Mortality Weekly Report 47:1073-1076 & 1083, 1998.

SIMIAN AGENT 8 (SA8)

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.

References:

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

HERPESVIRUS PAPIO 2

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.

References:

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

Eberle R, et al. Herpesvirus papio 2, an SA8-like -herpesvirus of baboons. Arch Virol 140:529-545, 1995.

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.

SIMIAN VARICELLA VIRUS

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.

References:

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.

HERPESVIRUS SAIMIRI

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.

References:

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.

HERPESVIRUS TAMARINUS

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.

References:

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.

HERPESVIRUS ATELES

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.

References:

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.

RHESUS RHADINOVIRUS

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.

References:

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.

HERPES SIMPLEX VIRUS

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.

References:

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.

CYTOMEGALOVIRUS

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).

References:

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.

EPSTEIN-BARR VIRUS

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.

References:

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.

Baskin, G. B., L. N. Martin, S. R. S. Rangan, B. J. Gormus, M. Murphey-Corb, R. H. Wolf and K. F. Soike. (1986) Transmissible lymphoma and simian acquired immunodeficiency syndrome in rhesus monkeys. J Natl Cancer Inst, 77, 127-139.

Li, S. L., P. Biberfeld and I. Ernberg. (1994) DNA of lymphoma-associated herpesvirus (HVMF1) in SIV-infected monkeys (Macaca fascicularis) shows homologies to EBNA-1, -2, and -5 genes. Int J Cancer, 59, 287-95.

Li, S. L., H. Feichtinger, E. Kaaya, P. Migliorini, P. Putkonen, G. Biberfeld, J. M. Middeldorp, P. Biberfeld and I. Ernberg. (1993) Expression of Epstein-Barr-virus-related nuclear antigens and B-cell markers in lymphomas of SIV-immunosuppressed monkeys. Int J Cancer, 55, 609-615.

Feichtinger, H., S. L. Li, E. Kaaya, P. Putkonen, K. Grunewald, K. Weyrer, D. Bottiger, I. Ernberg, A. Linde, G. Biberfeld, et al. (1992) A monkey model for Epstein Barr virus-associated lymphomagenesis in human acquired immunodeficiency syndrome. J Exp Med, 176, 281-286.

ENCEPHALOMYOCARDITIS VIRUS

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.

References:

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.

MONKEYPOX

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.

References:

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.

YABA POX

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.

References:

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.

BENIGN EPIDERMAL MONKEY POX (TANAPOX, OrTeCa POX)

Etiology: Tana poxvirus (unrelated to smallpox)

Transmission:

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.

MOLLUSCUM CONTAGIOSUM

Etiology: poxvirus unrelated to smallpox

Transmission:

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.

References:

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

MEASLES

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:

Potkay S, et al. An epizootic of measles in a colony of rhesus monkeys (Macaca mulatta). Am J Vet Res 27:331-334, 1966.

Shishido A. Natural infection of measles virus in laboratory monkeys. Jpn J Med Sci Biol 19:221-222, 1966.

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

Renne Ra, et al. Measles virus-associated endometritis, cervicitis, and abortion in a rhesus monkey. J Am Vet Med Assoc 163:639-641, 1973.

Remfry J. A measles epizootic with 5 deaths in newly imported rhesus monkeys (Macaca mulatta). Lab Anim 10:49-57, 1976.

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

MacArthur JA, et al. Measles in monkeys: an epidemiological study. J Hyg 83:207-212, 1979.

Albrecht P, et al. Fatal measles infection in marmosets: pathogenesis and prophylaxis. Infect Immun 27:969-978, 1980.

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.

CALLITRICHID HEPATITIS

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

ADENOVIRUS

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".

References:

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.

PAPILLOMAVIRUS

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.

References:

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.

FOCAL EPITHELIAL HYPERPLASIA OF CHIMPANZEES

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.

References:

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.

SV40

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). PML probably represents a reactivated latent infection, whereas pneumonia, nephritis, and meningeoencepLesions in brain may have typical distribution of PML or may be around ventricles (particularly in brainstem) and in superficial cortex. Astrocytes and oligodendrocytes are infected. Large basophilic intranuclear inclusions in lung, oligodendroglia, renal tubular epithelium.

References:

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.

Horvath CJ, et al. Simian virus 40-induced disease in rhesus monkeys with simain acquired immunodeficiency syndrome. Am J Pathol 140:1431-1440, 1992.

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.

Newman JS, et al. Identification of SV40 in brain, kidney, and urine of healthy and SIV-infected rhesus monkeys. J Neurovirol 4:394-406, 1998.

Lednicky JA, et al. Natural isolates of simian virus 40 from immunocompromised monkeys display extensive genetic heterogeneity: new implications for polyomavirus disease. J Virol 72:3980-3990, 1998.

Simon MA, et al. Association of simian virus 40 with a central nervous system lesion distinct from progressive multifocal leukoencepahlopathy in macaques with AIDS. Am J Pathol 154:437-446, 1999.

SIMIAN HEMORRHAGIC FEVER VIRUS

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.

References:

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.

EBOLA (RESTON)

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.

References:

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.

MARBURG

Etiology: Marburg virus (filovirus)

References:

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.

HEPATITIS A VIRUS

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.

References:

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.

HEPATITIS B VIRUS

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.

References:

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.

HEPATITIS C VIRUS

Etiology: Hepatitis C virus

Transmission:

Clinical: Only humans and chimpanzees susceptible.

Pathology:

References:

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.

SIMIAN PARVOVIRUS

Etiology: parvovirus related to human B19 parvovirus.

Clinical: Can cause transient anemia when experimentally inoculated into immunocompetent macaques. Progressive anemia has been observed in naturally infected macaques made immunodeficient by SRV or SIV.

Pathology: Dyserythropoiesis, intranuclear inclusion bodies in bone marrow

References:

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

O'Sullivan MG, et al. Clinical and epidemiological features of simian parvovirus infection in Cynomolgus macaques with severe anemia. Lab Anim Sci 46:291-297, 1996.

O'Sullivan MG, et al. Experimental infection of cynomolgus monkeys with simian parvovirus. J Virol 71:4517-4521, 1997.

RABIES

Etiology: Rabies virus

Clinical: Only 1 reported spontaneous case.

References:

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.

PRIMATE RETROVIRUSES

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

PRIMATE ONCOVIRUSES

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.

Although most infected animals remain latently infected and asymptomatic for life, STLV-I has been associated with lymphoma/leukemia in baboons, African green monkeys, and macaques by seroepidemiology or molecular biological techniques. HTLV-I/STLV-I do not contain recognized oncogenes and integrate monoclonally into the tumor-cell DNA of individuals, but randomly between individuals. Tumorigenesis has been linked to tax, a non-structural viral gene that activates cellular genes such as the IL-2 receptor (IL-2R). The relationship between cellular activation and tumorigenesis is poorly understood, making STLV-I in African species an important model for studying the pathogenesis of HTLV-I associated diseases in man. STLV-I appears to be nonpathogenic in Asian primates.

References:

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.

References:

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.

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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.

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PRIMATE LENTIVIRUSES (Retroviridae:lentivirinae)

HUMAN LENTIVIRUSES:

HIV-1 Worldwide

HIV-2 West Africa

NONHUMAN PRIMATE LENTIVIRUSES:

SIVmac Macaca mulatta (Rhesus)

SIVsmm Cercocebus torquatus atys (Sooty mangabey)

SIVmne Macaca nemestrina (Pigtailed macaque)

SIVagm/gri, SIVagm/tan, SIVagm/ver Cercopithecus sp. (African green monkey)

SIVmnd Papio sphinx (Mandrill)

SIVstm Macaca arctoides (Stump-tailed macaque)

SIVcyn Macaca fascicularis (Cynomolgus monkey)

SIVcpz Pan troglodytes (Chimpanzee)

SIVWCM Cercocebus torquatus lunulatus (White- crowned mangabey)

SIVSYK Cercopithecus mitis (Sykes monkey)

SIVHU Cercocebus Macaca Homo

All retroviruses contain env, pol, and gag genes. Lentiviruses have additional regulatory genes: HIV-1/SIVCPZ contain vif, vpu, vpr, tat, rev, nef; HIV-2/SIVSMM/SIVMAC/SIVMNE/SIVSTM contain vif, vpx, vpr, tat, rev, nef; SIVAGM contains vif, vpx, tat, rev, nef; SIVMND 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. HIV-1 probably originated in chimpanzees and has apparently been transmitted to humans on several different occasions. The closest known virus is SIVcpz. 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-1IIIB, 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 TH 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 HIVLai(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.

References:

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.

Gao F, et al. Origin of HIV-1 in the chimpanzee Pan troglodytes troglodytes. Nature 397:436-441, 1999.

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 SIVsm, 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.

References:

Gao F, et al. Human infection by genetically diverse SIVsm-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/SIVSMM/SIVMAC/SIVSTM/SIVMNE; HIV-1/SIVCPZ; SIVAGM/SIVWCM; SIVMND; SIVRCM and SIVSYK) 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. SIVAGM 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/SIVMAC and HIV-1/SIVAGM 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. SIVMAC is closely related to SIVSMM and probably represents a cross-species infection