SAFETY TRIAL OF SINGLE-DOSE TREATMENTS WITH A COMBINATION OF IVERMECTIN AND DIETHYLCARBAMAZINE IN BANCROFTIAN FILARIASIS

A supervised safety trial of the treatment with a combination of ivermectin 400 mug.kg-1 (IVER 400) plus increasing doses of diethylcarbamazine (DEC), given simultaneously in single dose, was performed on five groups of Polynesian Wuchereria bancrofti carriers, 49 males aged 25 to 73 years, in whom microfilaremia ranged from 1 to 6,137 mf/ml. The trial was hospital-based, open, dose-escalating (1 group per week). Safety of an unchanging dose of IVER 400 and ascending doses of DEC were studied in the 5 following groups: group 1 - IVER 400 plus DEC 1 mg.kg-1, 12 patients; group 2 - IVER 400 plus DEC 3 mg.kg-1, 17 patients; group 3 - IVER 400 plus DEC 6 mg.kg-1, 10 patients. Two control groups were included in the study, group 4 - DEC 6 mg.kg-1 alone, 5 patients; group 5-: IVER 400 alone, 5 patients. Carriers were examined and questionned regarding their experience of adverse reactions, which were graded 0 to 3 according to severity, at 6, 12 and 24 hours and at 4 days after treatment. Biological examination was performed 4 days before and 4 days after treatment and included determination of microfilaremia, complete blood count, liver function tests and assessment of creatinine and urea levels. Adverse reactions were observed in 51 % of 49 carriers (1 5 of grade 1, 8 of grade 2, 2 of grade 3). None was considered serious and they all disappeared in 2 days. The main symptoms were fever greater-than-or-equal-to 37.5-degrees-C, myalgia, arthralgia, headache, asthenia, anorexia, vertigo and chills. Adverse reactions of patients were not significantly different between the rive groups. No important abnormality were observed in laboratory tests performed after treatment. In terms of immediate reduction of microfilaremia, a combination (IVER 400 plus DEC) appeared more effective than IVER 400 alone, the latter being more effective than DEC 6 alone. These results strongly suggest that a single dose of combination (IVER 400 plus DEC 6) may be considered for treatment of male adult W. bancrofti carriers. However, the value of this drug combination for long-term reduction of microfilaremia, or prevention of the appearance of chronic disease symptoms, requires fur-ther study. Safety trials in females and children are needed before considering the combination for mass treatments.