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A new method for assessing the bactericidal activity of antileprous drugs against My cobacterium leprae using the mouse footpad technique is described. This approach, referred to as the "proportional bactericidal test", has been devised to overcome some of the problems of interpretation caused by drug persistence or prolonged bacteriostasis after drug administration has ended. The bactericidal activity of several drugs against M. leprae has been determined using this approach and the results obtained compared with those previously reported using alternative methods.

STUDIES on the chemotherapy of experimental human leprosy were made possible in 1960 by the demonstration of a limited infection with Mycobacterium Zeprae in the mouse footpad (Shepard, 1960). To begin with they were based mainly on the continuous administration of drugs from the day of inoculation, and subsequent assessment of their ability to suppress the growth of small inocula of M. Zeprae Chang, 1962, 1964;Rees, 1965;Gaugas, 1967). These studies were later extended by an assessment of the therapeutic action of drugs on established infections (Shepard and Chang, 1967), the viability of the organisms after drug treatment being tested by the tedious procedure of subinoculation into new groups of mice. Shepard (1967~) reported a " kinetic " technique of detecting the bactericidal action of drugs based on the treatment of inoculated mice for a limited period and measuring the subsequent delay in growth of the leprosy bacilli. Any delay exceeding that accounted for by bacteriostasis during administration and subsequent excretion of the drugs is taken to indicate that the growth must have developed from a number of viable bacilli smaller than that inoculated and hence that there has been a bactericidal effect. Results obtained with this technique suggested, for example, that dapsone is bactericidal to M . Zeprae, but only after 60 or more days of treatment (Shepard, 1967a.Rifampicin, a recently synthesised derivative of rifamycin, has been shown to be active both in vitro and clinically against M . tuberculosis, with bactericidal action (Grumbach and Rist, 1967;Pallanza et al., 1967;Verbist et al., 1967). When tested in the mouse footpad system it was found to be highly active against M. Zeprae (Rees, Pearson and Waters, 1970;Hilson, Banerjee and Holmes, 1972). The minimal effective dosage of the drug was, however, not determined.The present paper reports the activity of rifampicin against three strains of M. leprae in the mouse footpad by continuous administration, and a comparison between dapsone and rifampicin by means of the kinetic method of Shepard. MATERIALS AND METHODSThe approach employed was to follow the growth of M . leprae in the footpad of control and of drug-treated mice, according to the method of Shepard and Chang (1962).

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