Geary Timothy G, Bourguinat Catherine, Prichard Roger K
Institute of Parasitology, McGill University, Ste-Anne-de-Bellevue, QC, Canada.
Top Companion Anim Med. 2011 Nov;26(4):186-92. doi: 10.1053/j.tcam.2011.09.004.
Reports of loss-of-efficacy (LOE) events in dogs infected with Dirofilaria immitis despite adherence to accepted prophylaxis regimens with a macrocyclic lactone anthelmintic are attracting considerable attention. It is crucially important to distinguish among several possible causes for these LOE reports, one of which is the evolution of resistance to these drugs in heartworms. We review here recent evidence at the molecular level that supports the hypothesis that parasites derived from LOE cases have experienced a strong selection event and that these populations are characterized by very high frequencies of single-nucleotide polymorphisms in a D. immitis gene encoding a P-glycoprotein transporter, comprised of homozygous guanosine residues at 2 locations ("GG-GG" genotype). Furthermore, an infected dog adopted to Canada from the southern United States harbored a microfilarial population that was insensitive to very high doses of macrocyclic lactones and was characterized by a high frequency of the GG-GG genotype associated with LOE cases. We propose that this case be defined as a drug-resistant heartworm infection and suggest that a simple assay for the existence of resistant parasites is a 7-day microfilariae suppression test, which can be performed in a veterinary clinic as part of an effort to document the geographic distribution of this phenotype.
尽管坚持使用大环内酯类驱虫药进行公认的预防方案，但感染犬恶丝虫的犬出现药效丧失（LOE）事件的报告正引起相当大的关注。区分这些LOE报告的几种可能原因至关重要，其中之一是犬恶丝虫对这些药物产生抗性的进化。我们在此回顾最近在分子水平上的证据，这些证据支持这样的假设：来自LOE病例的寄生虫经历了强烈的选择事件，并且这些群体的特征是在编码P-糖蛋白转运体的犬恶丝虫基因中，单核苷酸多态性频率非常高，在两个位置由纯合鸟苷残基组成（“GG-GG”基因型）。此外，一只从美国南部被带到加拿大的感染犬体内的微丝蚴群体对非常高剂量的大环内酯类药物不敏感，并且其特征是与LOE病例相关的GG-GG基因型频率很高。我们建议将此病例定义为耐药性犬恶丝虫感染，并建议一种用于检测耐药寄生虫存在的简单试验是7天微丝蚴抑制试验，该试验可在兽医诊所进行，作为记录这种表型地理分布工作的一部分。
