Experimental borderline lepromatous leprosy with intraneural erythema nodosum leprosum in a mangabey monkey (Cercocebus atys).

A sooty mangabey monkey (Cercocebus atys) was inoculated with Mycobacterium leprae and developed borderline lepromatous leprosy and intraneural erythema nodosum leprosum. Previously studied mangabeys have developed only disseminated lepromatous leprosy without reactions. This case broadens the spectrum of leprosy seen in experimentally inoculated animals and further characterizes the nonhuman primate model of leprosy.

Histopathological changes in the eyes of mangabey monkeys with lepromatous leprosy.

Leprosy is the third leading cause of preventable blindness; however, little is known about the spread of infection to the eye. We have studied the eyes of three sooty managabey monkeys. Two were experimentally infected with Mycobacterium leprae; the third was not infected. In one of the infected animals there was histopathological evidence of lepromatous leprosy as evidenced by a chronic inflammatory infiltrate at the limbus, and detection of acid-fast bacilli in the corneal stroma, blood vessel walls, and corneal nerves. The latter were damaged as a result of the bacillary invasion. Electron microscopy revealed involvement and distortion of keratocytes with M. leprae and invasion of the corneal stroma by macrophages containing bacilli. Both infected animals showed focal collections of lymphocytes in the superficial stroma of the conjunctiva and in the ciliary body. This is the first report of the ocular manifestations of leprosy in any primate, including man, in which the duration of infection is known.

A second sooty mangabey monkey with naturally acquired leprosy: first reported possible monkey-to-monkey transmission.

The existence of naturally acquired leprosy in a second sooty mangabey monkey has been documented. The disease has the clinical and histopathological characteristics of subpolar lepromatous leprosy (LLs), and microbiological studies thus far confirm the etiologic agent as Mycobacterium leprae. This mangabey had been housed in direct contact with the first mangabey in which naturally acquired leprosy was diagnosed in 1979. Clinical symptoms appeared in the second mangabey in 1986, almost 7 years after the appearance of skin lesions in the first monkey. It is likely that the second mangabey contracted leprosy from the first mangabey or that both animals contracted the disease by contact with an unknown common third source. This is the only known possible natural transmission of leprosy from monkey to monkey, and suggests that a potential zoonosis exists in wild monkeys that may serve as a reservoir for the disease in areas where human leprosy is endemic.

Leprosy as a zoonosis: an update.

Naturally-acquired leprosy has been reported in nine-banded armadillos captured in the southern United States, a chimpanzee from Sierra Leone, and in two "sooty" mangabey monkeys from Nigeria. A significant prevalence of leprosy in wild armadillos establishes this animal as a reservoir of M. leprae, and exposure to armadillos has been implicated as a source of leprosy in humans. Current evidence suggests that leprosy is a zoonosis in certain nonhuman primate species. Control and eradication programs for leprosy should take into consideration the possible influence of extra-human sources of M. leprae, especially zoonotic leprosy.

Experimental leprosy in African green monkeys (Cercopithecus aethiops): a model for polyneuritic leprosy.

Three African green monkeys (Cercopithecus aethiops) were inoculated intravenously and intracutaneously with Mycobacterium leprae derived from a naturally infected mangabey monkey. All developed cutaneous lesions at inoculation sites. One developed disseminated cutaneous lesions, while the cutaneous lesions in the other two regressed and eventually disappeared. The animals were examined at necropsy five years after inoculation. All three had active leprosy infection in peripheral nerves with extensive inflammation and fibrosis. The disease histologically resembled borderline-lepromatous leprosy. These findings add a new dimension to animal models of leprosy.

Experimental leprosy in a rhesus monkey: necropsy findings.

A 6-month-old male rhesus monkey (Macaca mulatta) was inoculated intravenously and intracutaneously with Mycobacterium leprae obtained from a naturally infected mangabey monkey. The animal developed generalized lepromatous leprosy, and was killed for pathological examination 56 months after inoculation. Lesions were observed in the skin, nasal mucosa, peripheral nerves, and peripheral lymph nodes, with relative sparing of viscera. The monkey was carefully evaluated for the retrovirus STLV-III infection and was found negative. The rhesus monkey thus provides another animal model for the study of leprosy.

The lepromin test in rhesus monkeys.

The lepromin test was studied in rhesus monkeys. Six control monkeys which had not been inoculated with Mycobacterium leprae, six monkeys with experimentally induced leprosy, and nine monkeys which had been inoculated with M. leprae but had not developed leprosy were evaluated with 1X, 10X, and 15X lepromin A, with 1X and 10X lepromin M (mangabey monkey derived), with 1X and 25X purified inactivated M. leprae, and with an armadillo mock lepromin. We found that the lepromin test is useful in rhesus monkeys, but that a higher concentration of antigen than is used in humans is required to induce a response in monkeys. Control monkeys appear to be lepromin negative. Animals which have been inoculated and which develop lepromatous leprosy are also negative. Monkeys which are experimentally inoculated with M. leprae and do not develop leprosy become lepromin positive. Monkeys with indeterminate leprosy have reactions intermediate between lepromatous and resistant animals. No monkeys reacted to armadillo tissue. Our results indicate that 10X lepromin A is a useful preparation for the lepromin testing of rhesus monkeys.

In situ characterization of T lymphocyte subpopulations in leprosy in the mangabey monkey.

Leprosy in the mangabey monkey is an experimental model which is similar both clinically and histologically to human lepromatous leprosy. The immunopathology of these diseases was compared using monoclonal antibodies against T lymphocyte subpopulations in frozen tissue sections with an immunoperoxidase technique. In both mangabey and human lepromatous granulomas OKT4 (or Leu 3a) and Leu 2a cells were scattered among macrophages with greater numbers of Leu 2a as compared with OKT4 (or Leu 3a) cells. The results suggest that from an immunopathological standpoint experimental leprosy in mangabeys will provide a suitable model for the investigation of the pathogenesis of human lepromatous leprosy and for the evaluation of new antileprosy vaccines.

Transmissible lymphoma and simian acquired immunodeficiency syndrome in rhesus monkeys.

Four rhesus monkeys (Macaca mulatta) were inoculated with a homogenate of a cutaneous lepromatous leprosy lesion from a mangabey monkey (Cercocebus atys). One died of B-cell lymphoma, and another died of an immunodeficiency syndrome. Cell suspensions prepared from the tumor and spleen of the monkey with lymphoma induced lymphoma or an immunodeficiency syndrome when inoculated into additional young rhesus monkeys. The immunodeficiency syndrome was similar to simian acquired immunodeficiency syndrome and consisted of opportunistic infections, lymphoid hyperplasia or atrophy, wasting, and syncytial cell formation. Mitogen responses and percentages of T4- and T8-positive lymphocytes were normal until the animals were moribund. Lymphoblastoid cell lines became established in vitro from tumor cell suspensions. These cells were infected with a herpesvirus related to Epstein-Barr virus. In addition, a retrovirus morphologically similar to human T-cell lymphotrophic virus type III (HTLV-III) and simian T-lymphotrophic virus type III (STLV-III) was isolated from one of the lymphoblastoid cell lines (LCL). Type D retroviruses could not be demonstrated in the monkeys in the transmission study; however, a retrovirus similar to that in the LCL was isolated from 4 animals by coculture of peripheral blood lymphocytes with the human cell line H9. These results suggest that this retrovirus, STLV-III/Delta, may be associated with the immunodeficiency syndrome in these macaques and may be of mangabey origin.

Experimental leprosy in the mangabey (Cercocebus atys): necropsy findings.

A mangabey monkey (Cercocebus atys) was inoculated intravenously and intracutaneously with acid-fast bacilli (AFB) from a mangabey with spontaneously acquired leprosy. It developed generalized lepromatous leprosy and died 46 months after inoculation. Necropsy revealed severe lepromatous infiltrates in the skin, nasal mucosa, peripheral nerves, and testicles. Internal organs were only minimally involved. The lesions seen at necropsy were very similar to those seen in untreated cases of human lepromatous leprosy. These findings further substantiate the mangabey monkey as a suitable animal model for the study of lepromatous leprosy.

Leprosy in a mangabey monkey--naturally acquired infection.

Naturally acquired leprosy was detected in an otherwise normal "sooty" mangabey monkey (Cercocebus atys). This animal was imported from West Africa in 1975 and developed clinical symptoms of leprosy in 1979. Histopathologic findings were those of subpolar-lepromatous to borderline-lepromatous leprosy in the Ridley-Jopling classification. The disease was progressive, with crippling neuropathic deformities of the hands and feet. The disease regressed under specific therapy. The etiologic agent was identified as Mycobacterium leprae by the following criteria: invasion of nerves of host, staining properties, electron microscopic findings, noncultivable on mycobacteriologic media, DOPA-oxidase positive, lepromin reactivity, infection patterns in mice and armadillos, sensitivity to sulfone, and DNA homology. We believe the animal acquired the disease from a patient with active leprosy. The mangabey monkey offers promise as a primate model for leprosy, and adds a third reported species to animals with naturally acquired leprosy.

Experimental leprosy in three species of monkeys.

Eleven mangabey monkeys inoculated with Mycobacterium leprae developed lepromatous-type leprosy. Nine of the mangabeys were inoculated with M. leprae isolated from a mangabey with naturally acquired lepromatous leprosy. Immune function was depressed in some of these animals after dissemination of the disease. Two mangabeys developed lepromatous leprosy after inoculation with human M. leprae passaged in an armadillo. Three rhesus and three African green monkeys inoculated with mangabey-derived M. leprae also developed lepromatous leprosy. Mangabeys may be the first reported nonhuman primate model for the study of leprosy. Rhesus and African green monkeys may also prove to be reproducibly susceptible to the disease.

Depression of lymphocyte responses to mitogens in mangabeys with disseminated experimental leprosy.

Mononuclear cells from mangabey monkeys with disseminated experimental leprosy had increasingly severe depression of blastogenic responses to phytohemagglutinin, concanavalin A, and pokeweed mitogen as the disease progressed. Blastogenic responses were not depressed in cells from mangabeys with more localized disease. Blastogenic responses of cells from normal mangabeys appeared to vary with a circannual rhythm. The demonstration of significant negative correlations between the blastogenic responses to mitogens and the percentages of OKT8+ cells suggested that the mangabey OKT8+ subset may contain cells with suppressor function. The depressed responses to mitogens by cells from monkeys with disseminated experimental leprosy were associated with relatively high percentages of OKT8+ cells. Polyclonal immunoglobulin plaque-forming cell responses to pokeweed mitogen were depressed in cells from experimentally infected mangabeys. The results indicated that defects in immune regulation may occur in experimental leprosy in mangabeys, similar in some respects to the defects that have been reported in human leprosy.

Electron microscopic study of leprosy in a mangabey monkey (natural infection).

Ultrastructural features of the leproma of a) a naturally infected mangabey monkey, and lepromas and liver of b) a passage mangabey monkey, c) a rhesus monkey, d) an African green monkey, and e) a nine-banded armadillo inoculated with leprosy bacilli isolated from the leproma of a naturally infected mangabey monkey were studied by the freeze-etching technique. The size, shape, and ultrastructural features of leprosy bacilli in the phagolysosomes of macrophages in all of these samples were essentially the same as those in humans, nude mice, and armadillos inoculated with human Mycobacterium leprae. Distinct accumulations of small spherical droplets were observed around leprosy bacilli inside lepra cells of all the samples but were scarce in the specimen from the green monkey. The bacilli in all samples were long and slender, and had band structures on the smooth cell wall surfaces. The bacilli were indistinguishable from M. leprae.

Modelos de lepra multibacilar en huéspedes no alterados: estado actual / Multibacillary models of leprosy in not changed hosts: actual status

Se ha reportado lepra diseminada multibacilar en sujetos no alterados en tres especies de armadillos, chimpancés, monos mangabey, mono rhesus,, mono africano verde, ratas y ratones desnudos. No se ha demostrado que el chimpancé sea constantemente susceptible y por lo tanto requiere ser más estudiado para establecer su potencial utilidad. Los armadillos, debido a su facilidad de acceso, por lo menos en el Hemisferio Occidental, tienen grandes potenciales para experimentación, pero su utilidad en casi todas las áreas de experimentación casi no ha sido estudiada. Los ratones y las ratas desnudos tienen la ventaja de estar disponibles para laboratorios con el equipo adecuado; sin embargo, su cuidado es tedioso, su mantenimiento costoso y estos animales tienen vidas relativamente cortas. Las infecciones en los ratones desnudos parecen ser muy intensas y son, como las del armadillo, más graves que en la mayoría de los pacientes con lepra. Además, estos roedores, aunque no están alterados artificialmente, tienen una deficiencia inmunológica genética establecida en contraste con el sistema inmune de los individuos susceptibles a la lepra. El mono mangabey, aunque todavía en las etapas iniciales de experimentación, parece ofrecer la mejor esperanza hoy en día como modelo ideal para la lepra. Las únicas desventajas inmediatas son el ministro relativamente escaso de este animal y el costo de mantenimiento. Una enorme ventaja es la cercanía de esta especie a la especie humana. Las características de la enfermedad observada hasta el momento en los cinco sujetos estudiados sugieren que habrá muchas similitudes entre la lepra en el mono y el humano. El tiempo y los estudios los dirán