Mycobacterium leprae and Mycobacterium lepraemurium infections in domestic and wild animals.

Mycobacterium leprae, the aetiological agent of leprosy in humans, gives rise to a chronic granulomatous disease that affects primarily the skin and peripheral nerves, and secondarily some internal organs such as the testis and the eye; viscera are seldom involved. Depending on host resistance, leprosy may present as a benign disease (tuberculoid leprosy) or as a malignant disease (lepromatous leprosy), with a spectrum of intermediate stages appearing between the two. Immunity against leprosy depends on the cell-mediated immunity of the host, and this is severely compromised in the malignant (lepromatous) form of leprosy. Although culture of M. leprae has never been achieved in artificial media, the bacterium may be grown in several experimental animals, including the armadillo, non-human primates, and to a certain extent, rodents. Naturally acquired leprosy has been reported in wild nine-banded armadillos (Dasypus novemcinctus) and in three species of non-human primates (chimpanzees [Pan troglodytes], sooty mangabey monkeys [Cercocebus atys] and cynomolgus macaques [Macaca fascicularis]), thus qualifying leprosy as a zoonosis. Murine leprosy is a leprosy-like disease of rats and mice, caused by Mycobacterium lepraemurium. The disease affects primarily viscera and the skin, and very rarely peripheral nerves. Depending on the host strain, rodent leprosy may also evolve as 'lepromatous' or 'tuberculoid' leprosy, and strains of mouse that develop intermediate forms of the disease may exist. Growth of M. lepraemurium on conventional media for mycobacteria is not successful, but the bacterium has been cultured on an egg yolk-based medium. Naturally acquired murine leprosy has been observed in rats, mice and cats, but not in humans or any other species. Thus, in contrast to human leprosy, murine leprosy is not a zoonosis.

Immunization of highly susceptible C3H mice with ultrasonicated Mycobacterium lepraemurium (MLM) bacilli facilitates the development of increased resistance during MLM infection.

C3H mice were immunized subcutaneously with water soluble antigens of ultrasonicated Mycobacterium lepraemurium bacilli (MLMSon-S) in Freund's incomplete adjuvant (FIA) and challenged with 1 X 10(6)-1.25 X 10(8) live MLM bacilli inoculated into the foot pad. No swelling of the infected foot pad and no differences in bacillary multiplication and dissemination between the immunized mice and the control animals were observed in the first nine weeks. From nine weeks on, a small foot pad swelling developed in the immunized mice. Twenty weeks after inoculation, the number of bacilli in the foot pad, the popliteal lymph node, and the spleen was significantly lower in the immunized mice than in the normal controls after challenge with the lowest bacillary doses. Cyclophosphamide (CY) pretreatment did not increase the effect of immunization. The addition of MLM cell wall fragments to the emulsion used for immunization tended to increase the difference between immunized and normal animals, while no further increase of the immunization effect was obtained by the use of Freund's complete adjuvant (FCA). A tendency toward a plateau phenomenon for the multiplication of MLM bacilli was observed in the normal mice. In nonimmunized mice, CY treatment caused some reduction in bacillary numbers in the foot pads, and reinfection experiments suggested that a small reduction in susceptibility had been induced by the priming infection. Although unable to prevent a progressive course of the infection, genetically low-resistant C3H mice were able to modify the development of the infection by mechanisms that were activated by the infection itself. Similar mechanisms were facilitated by immunization with MLMSon-S.

Effect of BCG vaccination on Mycobacterium lepraemurium infection in a highly susceptible inbred mouse strain.

Upon infection with Mycobacterium lepraemurium (MLM) C3H mice develop a disease that has features in common with lepromatous leprosy in man. Intraperitoneal vaccination with a single dose of BCG four weeks before inoculation with MLM in the footpad significantly reduced the total bacillary load of the animals. In vaccinated animals there was a delay in the dissemination of bacilli to the popliteal lymph node, liver, and spleen. The growth rate of MLM in the footpad and the popliteal lymph node was not altered by BCG vaccination. Reduced dissemination of the bacilli seems to be a sensitive parameter of resistance in murine leprosy. The mechanism of the resistance observed is discussed mainly in relation to non-specific macrophage activation and T-cell mediated responses to cross-reactive antigens.