AVERMECTIN INHIBITION OF LARVAL DEVELOPMENT IN HAEMONCHUS-CONTORTUS -EFFECTS OF IVERMECTIN RESISTANCE

Avermectin (AVM inhibition of the development of the free-living stage s of Haemonchus contortus has been quantified in an assay in which nem atode eggs are placed on an agar matrix containing serial dilutions of a drug in the wells of a microtitre plate. Development is allowed to proceed for 6 days by which time larvae in control wells (no drug) hav e reached the infective, third (L3) stage. At high concentrations (>30 nM) ivermectin (IVM) paralyses L1 larvae soon after hatching, however , much lower concentrations (similar to 1 nM) are sufficient to inhibi t development to the L3 stage which suggests that effects of the drug other than those relating to gross motor activity are responsible for the latter effect. The larval stages of IVM-susceptible H. contortus i solates from both Australia and South Africa, including isolates known to be resistant to levamisole or rafoxanide and/or the benzimidazoles , were equally sensitive to inhibition by AVMs. In contrast, 6 isolate s of H. contortus resistant to IVM in vivo showed a reduced sensitivit y to AVM inhibition of development. The order of potency of a limited range of AVMs as inhibitors of larval development was consistent with in vivo efficacy. Resistance ratios for IVM-resistant isolates were de pendent on AVM structure, with AVM B2 the most sensitive probe for IVM resistance in the isolates tested.