Does dapsone resistance really matter in the MDT era?
To the Editor:
In a Letter to the Editor (4), Dr. Paul W. Roche and his colleagues presented the results of drug susceptibility testing of 268 clinical isolates of Mycobacterium leprae by means of the mouse foot pad technique between 1987 and 1999 at Anandaban Leprosy Hospital. Kathmandu, Nepal. Their results are interesting. However, their opinion about the significance of high-level, primary resistance to dapsone (DDS) in the era of multidrug therapy (MDT) is open to argument.
Roche, el al., proposed that "It will be important to monitor the trends in the level of resistance as well as the frequency of primary dapsone resistance . . ." (J), because "MDT efficacy could be severely compromised if high-level primary dapsone resistance becomes highly prevalent." (4). Infact, the MDT regimens, i.e.. two drugs [DDS and rifampin (RMP)] for paucibacillary (PB) leprosy and three drugs (DDS, clofazimine and RMP) for multibacillary (MB) leprosy, were designed on the principle that they would be effective against all the strains of M. leprae regardless of their susceptibility to DDS (6). Hence, whether the global prevalence of DDS resistance is increasing or declining is virtually irrelevant to the therapeutic effect of MDT (5), and there is no need to closely monitor trends of resistance to DDS.
Roche and his co-authors expressed their concern regarding the gradual disappearance of mouse foot pad laboratories (4). Unfortunately, for various reasons, this is probably an irreversible trend; sooner or later, the susceptibility of M. leprae to drugs will be tested by molecular genetic methods (1, 2) rather than by the mouse foot pad technique. Moreover, instead of DDS-resistance, one should pay attention especially to resistance to RMP. by far the most powerful bactericidal drug against M. leprae (3), and an irreplaceable component of the MDT regimens.
-Baohong Ji, M.D.
Bactériologie et Hygiene
Faculte de Médecine Pitié-Salpêtrière
Paris, France
REFERENCES
1. Honoré, N. and Cole, S. T. Molecular basis of rifampin resistance in Mycobacterium leprae. An- limicrob. Agents Chemother. 37(1993)414-118.
2. Honoré, N., Perani, E., Telenti, A., Grosset, J. and Cole, S. T. A simple and rapid technique for the detection of rifampin resistance in Mycobacterium leprae. Int. J. Lepr. 61(1993)600-604.
3. Ji. B., Perani, E., Petinom. C. and Grosset J. H. Bactericidal activities of combinations of new drugs against Mycobacterium leprae in nude mice. Antimicrob. Agents Chemother. 40(1996)393-399.
4. Roche. P. W., Neupane, K. D., Failbus, S. S. and Butlin, C. R. Dapsone drug resistance in the MDT era. (Letter) Int. J. Lepr. 68(2000)323-325.
5. WHO Expert Committee on Leprosy. Seventh report. Geneva: World Health Organization, 1998. Tech. Rep. Ser. 874.
6. WHO Study Group. Chemotherapy of leprosy for control programmes. Geneva: World Health Organization. 1982. Tech. Rep. Ser. 874.