Role of P-glycoprotein in Haemonchus contortus anthelmintic resistance.

The gastrointestinal parasite, Haemonchus contortus, is of major concern in the sheep and goat industry as well as in zoological settings. Over the years this parasite has developed resistance to the three classes of anthelmintics, benzimidazoles, imidazothiazoles and macrocyclic lactones, that are currently used for treatment. One of the mechanisms proposed to be involved in this resistance is the efflux transporter P-glycoprotein (Pgp). In this study, the resistance status of several strains of H. contortus was evaluated using the larval development assay DrenchRite?. After documenting the resistance status of these strains, transcription of Pgp in L3 larvae after exposure to anthelmintics was quantitated using polymerase chain reaction (PCR). Of the strains analyzed, only one was determined to be susceptible to all of the anthelmintics tested, while the others showed variable levels of resistance to one or more. A Haemonchus strain acquired from a giraffe at a zoo in Florida was the most resistant, showing extremely high levels of resistance to benzimidazoles and levamisole. Molecular characterization of the 18S rRNA gene and the internal transcriber spacer region (ITS) were performed on the giraffe strain to identify the species. Although there were variations in the isolate sequences, the most likely species for the giraffe strain was H. contortus. No transcription of Pgp was identified in H. contortus L3 larvae under the conditions of this study. Thus, increased Pgp does not appear to be a primary mechanism of drug resistance in this stage of the worm.