Search

Drug resistance surveillance identified six untreated leprosy patients in the Philippines with Mycobacterium leprae folP1 mutations which confer dapsone resistance. Five patients share a village of residence; four who carried the mutation, Thr53Val, were also linked by M. leprae variable-number tandem repeat (VNTR) strain types. In India, folP1 mutations were detected in two relapse patients with a history of dapsone treatment. Mutations were not found in the rifampin target gene rpoB. These findings indicate that dapsone resistance is being transmitted.

Patients with borderline-lepromatous (BL) or fully lepromatous (LL) leprosy were treated in the sanitarium for approximately 1 year with oral rifampin (600 mg daily) or with oral dapsone (100 mg daily). They were then treated as outpatients with intramuscular acedapsone (225 mg every 12 weeks) or oral dapsone (50 mg daily). They have now been followed for a total of 28 to 34 months. Death of Mycobacterium leprae during the initial 24 weeks was monitored by mouse inoculation with M. leprae from skin punch biopsy specimens. With rifampin therapy, death of M.leprae occurred rapidly, and viable M. leprae were nearly undetectable by the time the first specimen was taken after the start of treatment, at 4 weeks. With dapsone therapy, death of M. leprae was slower, and in some cases the inoculation results were still positive at 12 weeks. The therapeutic response during the period of outpatient treatment has been satisfactory. The number of dead M. leprae, as measured by the bacterial index in skin smears and the number of acid-fast bacteria in skin specimens, has continued to decrease, and clinical progress has been satisfactory. The measured drug-induced death of M. leprae occurred at about the same rate in BL patients as in LL patients. Disappearance of dead M. leprae from the tissues was much more rapid in BL patients than in LL patients.