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 iverm ectin 400 mug.kg-1 (IVER 400) plus increasing doses of diethylcarbamaz ine (DEC), given simultaneously in single dose, was performed on five groups of Polynesian Wuchereria bancrofti carriers, 49 males aged 25 t o 73 years, in whom microfilaremia ranged from 1 to 6,137 mf/ml. The t rial was hospital-based, open, dose-escalating (1 group per week). Saf ety 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; g roup 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 ques tionned regarding their experience of adverse reactions, which were gr aded 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 a nd 4 days after treatment and included determination of microfilaremia , complete blood count, liver function tests and assessment of creatin ine and urea levels. Adverse reactions were observed in 51 % of 49 car riers (1 5 of grade 1, 8 of grade 2, 2 of grade 3). None was considere d serious and they all disappeared in 2 days. The main symptoms were f ever greater-than-or-equal-to 37.5-degrees-C, myalgia, arthralgia, hea dache, asthenia, anorexia, vertigo and chills. Adverse reactions of pa tients were not significantly different between the rive groups. No im portant abnormality were observed in laboratory tests performed after treatment. In terms of immediate reduction of microfilaremia, a combin ation (IVER 400 plus DEC) appeared more effective than IVER 400 alone, the latter being more effective than DEC 6 alone. These results stron gly suggest that a single dose of combination (IVER 400 plus DEC 6) ma y be considered for treatment of male adult W. bancrofti carriers. How ever, the value of this drug combination for long-term reduction of mi crofilaremia, or prevention of the appearance of chronic disease sympt oms, requires fur-ther study. Safety trials in females and children ar e needed before considering the combination for mass treatments.