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Bactericidal action of dapsone against Mycobacterium leprae in mice
Abstract:
Dapsone (4,4'-diaminodiphenylsulfone), incorporated into the mouse chow in a concentration of 0.1 g/100 g of diet, was administered for 1 week to mice in which Mycobacterium leprae had multiplied to the level of 10(6) organisms/footpad. M. leprae were harvested from these and also from control mice, diluted serially, and inoculated into additional mice. The organisms recovered from untreated mice multiplied in passage with a mean doubling time of 12.2 days, and 35% or more of the inoculated organisms were viable, i.e., capable of infecting mice. Growth curves of M. leprae recovered from dapsone-treated animals lagged behind those of organisms from control animals by an average of 78 days, equivalent to 98.8% killing. Foot-by-foot harvests showed that only 0.2% of the M. leprae recovered from treated mice were viable, suggesting that treatment of mice with dapsone had been accompanied by killing of 99.4% of the viable M. leprae.
Insights
Dapsone treatment significantly reduced viable Mycobacterium leprae in mice. This study shows dapsone (4,4'-diaminodiphenylsulfone) effectively killed over 99% of leprosy bacilli, aiding in controlling infection.
Area of Science:
- Microbiology
- Pharmacology
- Infectious Diseases
Background:
- Leprosy, caused by Mycobacterium leprae, remains a significant global health challenge.
- Dapsone is a key antimicrobial drug used in multidrug therapy for leprosy.
- Assessing the in vivo efficacy of dapsone against M. leprae is crucial for treatment strategies.
Purpose of the Study:
- To evaluate the killing efficacy of dapsone on Mycobacterium leprae in a murine model.
- To determine the viability and infectivity of M. leprae after dapsone treatment in mice.
Main Methods:
- Mice infected with Mycobacterium leprae were treated with dapsone (0.1 g/100 g diet) for one week.
- Mycobacterium leprae were harvested from treated and control mice.
- Organisms were serially diluted and inoculated into new mice to assess viability and multiplication rates.
Main Results:
- M. leprae from untreated mice showed normal multiplication (12.2 days doubling time) with 35% viability.
- M. leprae from dapsone-treated mice exhibited significantly delayed growth, indicating 98.8% killing.
- Post-treatment harvests revealed only 0.2% viability of M. leprae, signifying a 99.4% reduction in viable organisms.
Conclusions:
- Dapsone administration in mouse chow is highly effective in killing Mycobacterium leprae in vivo.
- The study demonstrates dapsone's potent bactericidal activity against M. leprae, supporting its role in leprosy treatment.
- Results highlight the significant impact of dapsone on reducing viable M. leprae populations in infected hosts.