Conder G A, Johnson S S, Guimond P M, Geary T G, Lee B L, Winterrowd C A, Lee B H, DiRoma P J
Upjohn Company, Kalamazoo, Michigan 49001.
J Parasitol. 1991 Feb;77(1):83-6.
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.
绵羊的毛圆线虫通常被鉴定为对左旋咪唑具有抗性。已经开发出体外试验来研究捻转血矛线虫对左旋咪唑的抗性,但尚未确定该物种的体内模型。为了确定捻转血矛线虫/沙鼠(长爪沙鼠)模型在检测左旋咪唑抗性方面的实用性,对免疫抑制的沙鼠接种约1000条脱鞘感染性捻转血矛线虫幼虫(对左旋咪唑耐药或敏感),在接种后第10天经口用盐酸左旋咪唑或该药物的类似物进行治疗,并在接种后第13天处死。取出胃,纵向打开,在37℃蒸馏水中孵育5小时,固定在甲醛溶液中,并储存以备后续显微镜检查。对于敏感菌株,引起清除率大于或等于93.5%的左旋咪唑及其类似物剂量,清除的耐药虫体小于或等于68.9%。这些数据与这些药物对秀丽隐杆线虫野生型和左旋咪唑抗性菌株的活性一致。因此,捻转血矛线虫/沙鼠模型为研究对左旋咪唑以及可能对其他驱虫药的抗性提供了一种有用的体内工具。