Activity of combinations of dapsone, rifampin, minocycline, clarithromycin, and sparfloxacin against M. leprae-infected mice.

In these studies we evaluated the activity of low levels of five antimicrobials against Mycobacterium leprae-infected mice when administered singly and in all possible two- and three-drug combinations. Antibiotics studied were: dapsone (D) 0.0001% in the diet, rifampin (R) 20 mg/kg by gavage once monthly, minocycline (M) 0.004% in the diet, clarithromycin (C) 0.001% in the diet, and sparfloxacin (S) 5 mg/kg by gavage five times weekly. Singly each agent was found bacteriostatic (D + R) or partially bactericidal (M, C, and S) but not fully bactericidal. All 10 two-drug regimens were found at least bacteriostatic, 2 being "partially bactericidal" and 4 being "fully bactericidal." Of the 10 three-drug regimens, 9 were found "fully bactericidal" and the other "partially bactericidal." We conclude that combinations of antibiotics active against M. leprae are generally additive in combination.

Transmission of leprosy in nude mice through thorn pricks.

The dorsum of the feet of 10 nude mice was smeared with 10(7) Mycobacterium leprae and then pricked with cactus thorns contaminated with M. leprae. In 15 months five of them developed lepromatous nodules at the infected site and disseminated lesions in the ears, nose, tail and the organs of the reticuloendothelial system. Penetrating injuries through unprotected skin contaminated with M. leprae from the environment may play a role in the transmission of leprosy in humans.

Adoptively transferred reactivity to M. leprae in nude mice infected with M. leprae.

Reversal reactions are manifestations of delayed hypersensitivity to M. leprae and are thought to be usually accompanied by manifestations of effective cell-mediated immunity (CMI) as measured by bacterial clearing. These experiments were designed to study the induction of reversal reactions in M. leprae-infected, congenitally athymic nude mice using adoptive transfer of CMI. Splenic cell suspensions derived from unimmunized heterozygous nu/+ mice, and those vaccinated with heat-killed M. leprae, viable BCG and a mixture of the two antigens were diluted to contain 10(4), 10(5), 10(6), 10(7) lymphocytes/0.1 ml and infused intravenously into multibacillary nude mice. The production of reversal reactions in leprous nude mice in response to adoptively transferred CMI was studied in a quantitative fashion. Dose responsive induction of reversal reactions, apparent by footpad inflammation and swelling, decreased morphological indices (MI) of the bacteria and mononuclear cell infiltrations, histopathologically, were observed. For nude mice receiving cells primed with 3.9 X 10(5) living BCG alone, the effective dose 50% (ED50) was 1.0 x 10(6) lymphocytes to induce reversal reactions. For those receiving cells primed with 10(7) M. leprae the ED50 was 3.7 x 10(5) lymphocytes. For nude mice receiving cells primed with a mixture consisting of 1/2 the above dose of BCG + 1/2 the above dose of M. leprae, the ED50 was 6.8 x 10(4) lymphocytes.

Transmission of leprosy in nude mice.

Nude mice in groups of 10 were exposed to M. leprae by subcutaneous injection and topically through the nose, lungs, mouth, stomach and skin, broken and unbroken. Animals injected subcutaneously and those topically exposed to M. leprae through the nose developed localized disease which in the course of time became generalized. The nose seems to be the site of entry of M. leprae in this model. To the extent that these results can be generalized to humans exposed to M. leprae, it would seem that leprosy bacilli impact topically on the nasal mucosa or are inoculated subcutaneously.

Invasion of liver parenchymal cells by Mycobacterium leprae in an experimentally infected nude mouse. An electron microscopic study.

Liver tissue from a nude mouse infected with Mycobacterium leprae for 18 months was examined using light and electron microscopes. Numerous microgranulomas composed of macrophages were present throughout the liver. M. leprae in large numbers were present in Kupffer cells, macrophages, endothelial cells, and liver parenchymal cells. The study shows that the lower temperature of about 31 degrees C optimal for the growth of M. leprae is relative rather than absolute, and that M. leprae can invade even liver cells.