In vitro assessment of the activity of anthelmintic compounds on adults of Onchocerca volvulus.
The viability of adult Onchocerca volvulus and the effect of 12 known anthelmintic compounds on the parasites have been evaluated in an in vitro culture system. Three different parameters, a colorimetric assay, using NADH-dependent reduction of a tetrazolium salt to dark blue formazan by living adult worms, motility indices of male worms and lactate excretion of female worms were used to determine worm viability. The experiments showed that over a short term period of six days the viability of the worms did not decline significantly. The use of males isolated by dissection of whole nodules for the evaluation of drug effects in vitro is preferable to collagenase isolated worms. Mel W, milbemycin a and d, ivermectin, levamisole, CGP 6140 and, to a lesser extent, suramin immobilized male worms or significantly reduced the motility indices at a concentration of 10 microM. The tetrazolium reduction by male worms was not affected by levamisole, whereas the other active compounds demonstrated significant inhibitory effects. Diethylcarbamazine, mebendazole, flubendazole, metrifonate and CGP 20376 had no significant effect on male viability. Comparable activity was seen with the intact female worms isolated by collagenase digestion. Mel W, the milbemycins and ivermectin significantly inhibited tetrazolium reduction, whereas suramin and the other compounds had only slight or no inhibitory effects on female O. volvulus. Although one still has to aim at an improvement of the culture conditions, the in vitro test system using adult O. volvulus provides a basis for further research on potential antifilarial compounds.
Strote
G
G
Department of Helminthology, Bernhard Nocht Institute for Tropical Medicine, Hamburg, FRG.
Wieland
S
S
Darge
K
K
Comley
J C
JC
D000818:Animals; D000871:Anthelmintics / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005260:Female; D008297:Male; D009068:Movement / Q000187:drug effects; D009854:Onchocerca / Q000187:drug effects* / Q000302:isolation & purification
D000871:Anthelmintics