Comparison of Ivermectin-Induced Paralysis of the Pharyngeal and Somatic Musculature of Ivermectin-Sensitive and -Resistant Strains of a Parasitic Nematode,Haemonchus Contortus
Hernández, Caterina Maria
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Nematodes that parasitize the mammalian gastrointestinal tract are a serious health problem in human and veterinary medicine. The use of drugs, called anthelmintics, to control these infectious organisms is most developed for ruminant animals. Currently, the primary class of anthelmintics used to treat ruminant nematodiases is termed the macrocyclic lactones, typified by Ivermectin. Unfortunately, as is the case for essentially all chemotherapeutic agents, resistance to Ivermectin has appeared in the field. In order to investigate this example of drug resistance, I focused my studies on a trichostrongylid parasite of ruminants, Haemonchus contortus, which is a large parasite and easily obtainable for laboratory use. The basis for Ivermectin resistance in H. contortus, as for other parasitic nematodes, is undefined. Ivermectin paralyzes both the somatic and pharyngeal muscular systems in nematodes, inhibiting movement and preventing oral ingestion of nutrients. These effects seem to be mediated through different receptors. To determine if either is more affected in resistant strains, this study compared the differential effects of Ivermectin on motility and pharyngeal function in Ivermectin-sensitive and -resistant strains of H. contortus. Using a radiometric assay to measure oral ingestion in adult parasites and an automated motility recorder to measure body wall paralysis, it was found that both parameters were less sensitive to the drug in the Ivermectin-resistant strain compared to the sensitive strain. Based on these results, it does not appear that Ivermectin resistance is mediated by the mutation of a tissue-specific receptor.