title: Relative potency of macrocyclic lactones in in vitro assays with larvae of susceptible and drug-resistant Australian isolates of Haemonchus contortus and H. placei.
abstract: The present study used in vitro assays to determine the relative potency of commercial macrocyclic lactone (ML) anthelmintics against larvae of drug-susceptible and drug-resistant Australian isolates of important parasites of sheep and cattle, Haemonchus contortus and Haemonchus placei, respectively. Cattle pour-on products containing abamectin, ivermectin, eprinomectin, doramectin or moxidectin were diluted in DMSO and used in larval development assays. Abamectin was the most potent chemical (lowest IC50 value) towards the drug-susceptible H. contortus Kirby isolate. The abamectin IC50 was approximately 2-fold lower than those for ivermectin, moxidectin, eprinomectin and doramectin. Moxidectin and abamectin were the most potent chemicals towards the resistant H. contortus Wallangra isolate. This isolate showed resistance ratios up to 70-fold towards eprinomectin. The resistance ratio for this species was lowest with moxidectin (ratio of 4.0-fold). Abamectin was also the most potent chemical towards both drug-susceptible (Bremner) and drug-resistant (Dayboro) H. placei isolates. The larval development assay only showed low levels of resistance for the drug-resistant H. placei, with resistance ratios ranging from 1.7 to 2.0 fold for moxidectin and abamectin, up to 3.3-fold for eprinomectin. This study examined the readily-accessible larval life stages of these parasites in in vitro assays, and, hence, the relationship between our findings and relative drug efficacies in vivo remains to be determined. Despite this, the study accords with some evidence from the use of these anthelmintics in the field in demonstrating the potency of moxidectin and abamectin against ML-resistant H. contortus. The study also highlights the usefulness of eprinomectin as a readily-available compound which is a more sensitive marker for ML resistance in in vitro larval development assays than the other commercial ML compounds examined.
authors.affiliation: CSIRO Animal, Food and Health Sciences, Brisbane, QLD, Australia. Electronic address: andrew.kotze@csiro.au.
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Kotze
authors.affiliation: CSIRO Animal, Food and Health Sciences, Brisbane, QLD, Australia.
authors.forename: Angela P
authors.initials: AP
authors.lastname: Ruffell
authors.affiliation: CSIRO Animal, Food and Health Sciences, Armidale, NSW, Australia.
authors.forename: Malcolm R
authors.initials: MR
authors.lastname: Knox
authors.affiliation: Virbac, Sydney, NSW, Australia.
authors.forename: Gareth A
authors.initials: GA
authors.lastname: Kelly
mesh_terms: D000818:Animals; D000871:Anthelmintics / Q000494:pharmacology*; D001315:Australia; D004351:Drug Resistance / Q000187:drug effects; D006189:Haemonchus / Q000187:drug effects*; D020128:Inhibitory Concentration 50; D007783:Lactones / Q000494:pharmacology*; D007814:Larva / Q000187:drug effects
chemical_list: D000871:Anthelmintics; D007783:Lactones
keywords: Haemonchus contortus; Haemonchus placei; Larval development assay; Macrocyclic lactones; Resistance