Moxidectin remains efficacious against ivermectin-resistant Haemonchus contortus: comparative pharmacological assessment of single and double dose-responses

Abstract

Although the macrocyclic lactones ivermectin (IVM) and moxidectin (MXD) share some pharmacological properties, a differential pattern of efficacy against resistant nematodes has been described (Vickers et al., 2001). Enhanced drug concentration within the worm and improved efficacy against resistant Haemonchus contortus have been recently reported after the intraruminal administration of IVM compared to the subcutaneous treatment (Lloberas et al., 2012). This work aimed to assess the relationship between anthelmintic activity and host tissue/parasite exposure for IVM and MXD in lambs naturally-infected with resistant H. contortus. The influence of a 2-fold dosage on the drug concentrations achieved at the host (bloodstream, gastrointestinal content/tissues) and within H. contortus were simultaneously evaluated with the clinical efficacy. Forty eight (48) naturally parasitised lambs were assigned into four (4) experimental groups and intraruminally treated with either IVM or MXD at 0.2 and 0.4 mg/kg. Blood samples were collected over 14 days post-treatment. Parasitological post-mortem examination was done at day 15 post-treatment. The recovered worms were identified by species and counted. Additionally, mucosal and fluid content samples and adult specimens of H. contortus were recovered at day 1 post-treatment. IVM and MXD were measured by HPLC. Both IVM and MXD concentration profiles measured within H. contortus reflected those observed in the abomasal contents. In spite of the high concentrations recovered from the abomasal content and within the worm, IVM completely failed to control H. contortus (0% efficacy) at both dose rates. Oppositely, MXD efficacy against this IVM-resistant H. contortus strain was 94.2 (therapeutic dosage) and 99.1% (double dose). The improved drug exposure (target worm) achieved after the oral/intraruminal treatment compared to the subcutaneous injection (Lloberas et al., 2012), as well, as the advantageous MXD efficacy performance observed at twice the dose should be seriously considered to optimise nematode control before a complete therapeutic failure is observed.