title: Utility of a Haemonchus contortus/jird (Meriones unguiculatus) model for studying resistance to levamisole.
abstract: Trichostrongylid nematodes of sheep commonly are identified as exhibiting resistance to levamisole. In vitro assays have been developed to study levamisole resistance for Haemonchus contortus, but no in vivo model has been identified for this species. To determine the utility of a H. contortus/jird (Meriones unguiculatus) model for examining levamisole resistance, immunosuppressed jirds were inoculated with approximately 1,000 exsheathed infective larvae of H. contortus (resistant or susceptible to levamisole), treated per os on day 10 postinoculation (PI) with levamisole hydrochloride or analogs of the drug, and killed on day 13 PI. Stomachs were removed, opened longitudinally, incubated in distilled water at 37 C for 5 hr, fixed in formaldehyde solution, and stored for subsequent microscopic examination. Doses of levamisole and its analogs, which elicited percentage clearances of greater than or equal to 93.5 for the susceptible strain, cleared less than or equal to 68.9% of the resistant worms. These data are consistent with activities for the drugs against wild-type and levamisole-resistant strains of Caenorhabditis elegans. Thus, the H. contortus/jird model provides a useful in vivo tool to study resistance to levamisole and possibly other anthelmintics.
authors.affiliation: Upjohn Company, Kalamazoo, Michigan 49001.
authors.forename: G A
authors.initials: GA
authors.lastname: Conder
authors.forename: S S
authors.initials: SS
authors.lastname: Johnson
authors.forename: P M
authors.initials: PM
authors.lastname: Guimond
authors.forename: T G
authors.initials: TG
authors.lastname: Geary
authors.forename: B L
authors.initials: BL
authors.lastname: Lee
authors.forename: C A
authors.initials: CA
authors.lastname: Winterrowd
authors.forename: B H
authors.initials: BH
authors.lastname: Lee
authors.forename: P J
authors.initials: PJ
authors.lastname: DiRoma
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004351:Drug Resistance; D005260:Female; D005849:Gerbillinae / Q000469:parasitology*; D006188:Haemonchiasis / Q000188:drug therapy*; D006189:Haemonchus / Q000187:drug effects*; D007978:Levamisole / Q000031:analogs & derivatives / Q000494:pharmacology* / Q000627:therapeutic use; D015394:Molecular Structure; D011897:Random Allocation
chemical_list: D007978:Levamisole