The effects of ivermectin used in combination with other known antiparasitic drugs on adult Onchocerca gutturosa and O. volvulus in vitro

Abstract

The effects of ivermectin at a concentration of 3·13 × 10 6 m used in combination with other antiparasitic drugs on the viability of adult Onchocerca in vitro were assessed using MTT colorimetry and worm motility levels. When ivermectin was used against male O. gutturosa over a 7 d period in combination with suramin (5 × 10 −5 m), CGP 6140 (3·13 × 10 −6 m), CGP 20376 (1·95 × 10 −7 m), mefloquine (3·13 × 10 −6 m), levamisole (3·13 × 10 −6 m), mebendazole (5 × 10 −5 m), flubendazole (5 × 10 −5 m) and albendazole (5 × 10 −5 m), there was either no increased effect or only a marginally increased effect on motility levels when compared with the use of ivermectin alone. MTT colorimetry revealed that in most cases there was a cumulative effect of the 2 drugs used in combination but not a synergistic effect. In a trial extended to 26 d it was demonstrated that the combination of ivermectin and suramin did not produce a greater inhibition of motility than ivermectin alone. Using female O. volvulus, the activity of ivermectin, CGP 6140 and the 2 drugs combined was examined. The motility of all 3 groups exposed to drug(s) was suppressed by 24 h compared with controls. MTT colorimetry performed on day 7, using the pre-weighed anterior end of each worm, illustrated that ivermectin alone produced a 43·4% inhibition of formazan formation compared with controls, CGP 6140 alone produced 50·6% inhibition, while the drug combination produced a 72% inhibition, equivalent to the heat-killed control. The cumulative effects seen with certain drug combinations in vitro should be examined in vivo, where they may have some practical value in the elimination of adult Onchocerca.