ethionamide and Erythema-Nodosum

Between 1980 and 1994, 67 new or relapsing leprosy patients were treated by daily administered multidrug regimens. Tuberculoid patients (23 TT/BT) received either bitherapy [rifampin + dapsone or clofazimine (RMP + DDS or CLO)] or tritherapy [RMP + DDS and/or CLO and/or ethionamide (ETH)] until clinical cure. Lepromatous patients (44 BB/BL/LL) received tritherapy (RMP + DDS and/or CLO and/or ETH) at least until bacteriological negativity. Of the 23 tuberculoid patients only one patient (5%) was cured at 6 months and about 70% needed between 6 and 24 months of treatment to obtain clinical cure (mean 19.5 months). In the 44 lepromatous patients, the achievement of bacteriological negativity was significantly linked to the initial bacterial index (BI), and it occurred after 2 to 7 years (mean 66.5 months) of multidrug therapy (MDT). The average BI decrease per year was 1.1+ during the first year, 0.9+ the second year, and then < 0.5+ per year. Reactional states significantly (p < 0.01) influenced the BI course: reversal reactions (RR) accelerated while erythema nodosum leprosum (ENL) delayed the BI decrease. Three of the 23 (13%) tuberculoid and 19 of the 44 (43%) lepromatous patients (p < 0.02) exhibited a RR and 18 of 44 (41%) lepromatous patients had ENL during MDT. A late RR (LRR) was observed in 1 (5%) and 6 (17%) of our tuberculoid and lepromatous patients, respectively, and 3 (8%) of our lepromatous patients suffered post-MDT ENL. No confirmed relapse has been observed within a follow-up period of 6 months to 7 years and 3 months [59 person-years at risk (PYR)] for TT/BT patients and of 4 months to 5 years and 10 months (100 PYR) for BB/BL/LL patients. When compared to the recommended WHO/MDT, it appears that daily MDT does not increase the clinical or the bacteriological cure rates either at 6 months in paucibacillary tuberculoid patients or at 2d years in multibacillary lepromatous patients. Moreover, as does the WHO/MDT, our regimens show a high frequency of reactional states both during and after treatment. This fact constitutes the main new problem of the actual treatment of leprosy.

Topics: Adolescent; Adult; Aged; Child; Child, Preschool; Clofazimine; Dapsone; Drug Resistance, Microbial; Drug Therapy, Combination; Erythema Nodosum; Ethionamide; Female; Follow-Up Studies; Humans; Leprostatic Agents; Leprosy, Borderline; Leprosy, Lepromatous; Leprosy, Tuberculoid; Male; Middle Aged; Recurrence; Rifampin

Melanesian leprosy patients from New Caledonia were studied for the following parameters during the course of polychemotherapy: peripheral blood T-cell subsets, as identified in an immunofluorescence assay with monoclonal antibodies OKT3 ("pan-T"), OKT4 ("helper/inducer"), and OKT8 ("cytotoxic-suppressor"), and anti-Mycobacterium leprae antibodies in the serum, as measured by the fluorescent leprosy antibody absorption test. A group of Melanesian healthy subjects with no known exposure to M. leprae served as controls. Healthy contacts of leprosy patients were also studied for the presence of anti-M. leprae antibodies. Untreated, nonreactional lepromatous patients displayed moderate but significant T-cell abnormalities, consisting of a decrease in the percentage of OKT3+ and OKT4+ cells with a decrease in the OKT4:OKT8 ratio. These abnormalities disappeared within nine months of treatment. A transient decrease in the percentage of OKT8+ cells with an increase in the OKT4:OKT8 ratio was seen in patients suffering erythema nodosum leprosum (ENL). Tuberculoid patients, whether treated or not, did not show any T-cell marker disturbances. Positive serological tests for anti-M. leprae antibodies were found in 100% of lepromatous patients, 92% of tuberculoid patients, and 56% of healthy contacts. No significant decline in the antibody titer was observed with treatment during the survey period.

Topics: Adolescent; Adult; Antibodies, Bacterial; Child; Clofazimine; Dapsone; Drug Therapy, Combination; Erythema Nodosum; Ethionamide; Fluorescent Antibody Technique; Humans; Leprosy; Middle Aged; Mycobacterium leprae; New Caledonia; Rifampin; T-Lymphocytes; T-Lymphocytes, Cytotoxic; T-Lymphocytes, Helper-Inducer; T-Lymphocytes, Regulatory

A systematic study was performed on the reactions occurring during several short-course therapy regimens for the treatment of paucibacillary and multibacillary patients. Most type 1 upgrading reactions in paucibacillary (PB) leprosy were mild to moderate and of short duration, while the time of onset was extremely variable. Their incidence was higher in the regimen rifampin (RMP) 900 mg once weekly for ten weeks than when a single dose of RMP 40 mg/kg body weight was given or 1500 mg in one dose followed by one year of dapsone (DDS) 100 mg daily. In multibacillary (MB) leprosy, three regimens were compared: MB-WHO regimen; regimen C, consisting of daily RMP 600 mg, ethionamide (ETH) 500 mg, and DDS or clofazimine (CLO) 100 mg for six months, followed by six months of daily DDS or CLO; and regimen D, identical to regimen C but comprising daily DDS or CLO plus ETH 500 mg during the second semester. Type 1 upgrading reactions occurred more frequently in MB patients and were more severe than in PB patients. They occurred more frequently and were more severe in regimens C and D than in the MB-WHO regimen. CLO 100 mg daily prevented type 1 reactions in MB patients and rendered them less severe. ENL was also more frequent in regimens C and D and was not prevented by CLO in the dosage used. Although there is some correlation between type 1 reactions and the total amount of RMP administered, other aspects of RMP administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Child; Clofazimine; Dapsone; Drug Therapy, Combination; Edema; Erythema Nodosum; Ethionamide; Female; Humans; Leprostatic Agents; Leprosy; Male; Neuritis; Prospective Studies; Rifampin

Topics: Adult; Animals; Clofazimine; Dapsone; Drug Resistance, Microbial; Erythema Nodosum; Ethionamide; Humans; Leprosy; Mycobacterium leprae; Patient Compliance; Prothionamide; Rifampin