Overcoming macrocyclic lactone resistance in Haemonchus contortus with pulse dosing of levamisole

The in vivo effect of dosing levamisole as a pulse release within an ivermectin (IVM) controlled-release device (CRD) was simulated by periodic dosing of levamisole to Haemonchus contortus-infected sheep already treated with an IVM CRD. The rationale for this treatment combination arises from the need to find alternative approaches to the treatment of gastrointestinal parasites in livestock in the face of increasing levels of anthelmintic resistance which is now widespread in Australia. Thirty merino sheep (4 months of age) were infected weekly with a mixture of susceptible and ivermectin resistant H. contortus beginning at Day 28. Twenty eight days after first infection, groups of 10 sheep were treated with IVM capsules alone, IVM capsules and an oral dose of levamisole (LEV) at Days 50 and 100 or no treatment. At pre-determined intervals, up to 126 days after treatment, faecal worm egg counts (FWEC) were determined and development rates of infective larvae (L3) cultured in faeces were measured. Haematological parameters and drug concentration in plasma were measured throughout the 100-day release period of the controlled-release device. Sheep were slaughtered at Day 135 for estimates of total worm burden. FWEC of sheep treated with IVM+LEV declined (99.9% reduction) after administration of oral LEV and were suppressed until Day 98. There was a significant difference (p<0.0001) in worm counts at slaughter between groups. The results demonstrate the potential advantage of combining a pulse of short-acting drug into the long-acting anthelmintic capsule to provide better parasite control than that achieved from the existing CRD treatment when IVM-resistant worms were present.