Moxidectin remains efficacious against ivermectin-resistant Haemonchus contortus. Comparative pharmacological assessment of double dose-responses.

LLOBERAS M. 2, ALVAREZ L.1, ENTROCASSO C.2, BALLENT M.1, VIRKEL G.,1 LANUSSE C.1, LIFSCHITZ A.1

Perth

Conferencia; 24th International Conference of the World Association for the Advancement of Veterinary Parasitology; 2013

World Association for the Advancement of Veterinary Parasitology

Although the macrocyclic lactones ivermectin (IVM) and moxidectin (MXD) share some pharmacological properties, a differential pattern of efficacy against resistant nematodes has been described (cita). 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 comparatively assess the relationship between anthelmintic activity and host tissue/parasite exposure (drug availability) for IVM and MXD in lambs naturally-infected with resistant H. contortus. The influence of a 2-fold dosage on the drug concentration profiles achieved in the host (bloodstream, gastrointestinal contents/tissues) and within H. contortus were simultaneously evaluated with the clinical efficacy of each treatment. Thirty (48) naturally parasitised lambs were assigned into four (4) experimental groups and intraruminally treated with either IVM or MXD at 0.2 mg/kg and 0.4 mg/kg. Blood samples were collected from six (6) animals in each treated group over 14 days post-treatment. Parasitological post-mortem examination was done at day 15 after treatments. The recovered adult abomasal worms were identified by species and counted. Four (4) animals from each group were sacrificed at day 1 post-treatment. Mucosal and fluid content samples from the abomasum and small intestine were collected. Adult specimens of H. contortus were recovered from the abomasum. 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 (host tissues and target worm) achieved after the oral/intraruminal treatment compared to the subcutaneous injection, as well, as the advantageous MXD efficacy performance observed at twice the dose (0.4 mg/kg) should be seriously considered to optimize nematode control before a complete therapeutic failure is observed. References M. Lloberas, L. Alvarez, C. Entrocasso, G. Virkel, C. Lanusse, A. Lifschitz., 2012. Exp. Parasitol., 131, 304-309.