Department of Infectious Diseases, University of Georgia, Athens, GA, 30602, USA; Center for Tropical and Emerging Global Diseases, University of Georgia, Athens, GA, 30602, USA.
Bayer Animal Health GmbH, 51373, Leverkusen, Germany.
Int J Parasitol Drugs Drug Resist. 2019 Aug;10:45-50. doi: 10.1016/j.ijpddr.2019.04.004. Epub 2019 Apr 26.
The macrocyclic lactone anthelmintics are the only class of drug currently used to prevent heartworm disease. Their extremely high potency in vivo is not mirrored by their activity against Dirofilaria immitis larvae in vitro, leading to suggestions that they may require host immune functions to kill the parasites. We have previously shown that ivermectin stimulates the binding of canine peripheral blood mononuclear cells (PBMCs) and polymorphonuclear leukocytes (PMNs) to D. immitis microfilariae (Mf). We have now extended these studies to moxidectin and examined the ability of both drugs to stimulate canine PBMC and PMN attachment to Mf from multiple strains of D. immitis, including two that are proven to be resistant to ivermectin in vivo. Both ivermectin and moxidectin significantly increased the percentage of drug-susceptible parasites with cells attached at very low concentrations (<10 nM), but much higher concentrations of ivermectin (>100 nM) were required to increase the percentage of the two resistant strains, Yazoo-2013 and Metairie-2014, with cells attached. Moxidectin increased the percentage of the two resistant strains with cells attached at lower concentrations (<10 nM) than did ivermectin. The attachment of the PBMCs and PMNs did not result in any parasite killing in vitro. These data support the biological relevance of the drug-stimulated attachment of canine leukocytes to D. immitis Mf and suggest that this phenomenon is related to the drug resistance status of the parasites.
大环内酯类驱虫药是目前唯一用于预防心丝虫病的药物类别。它们在体内的极高效力与其在体外对犬恶丝虫幼虫的活性并不相符，这表明它们可能需要宿主免疫功能来杀死寄生虫。我们之前已经表明，伊维菌素刺激犬外周血单核细胞（PBMC）和多形核白细胞（PMN）与犬恶丝虫微丝蚴（Mf）的结合。现在，我们已经将这些研究扩展到莫昔克丁，并检查了这两种药物刺激犬 PBMC 和 PMN 附着到来自多种犬恶丝虫株的 Mf 的能力，包括两种在体内被证明对伊维菌素有抗性的株。伊维菌素和莫昔克丁都显著增加了附着细胞的药物敏感寄生虫的百分比，在非常低的浓度（<10 nM）下，但需要更高浓度的伊维菌素（>100 nM）才能增加附着细胞的两种抗性株 Yazoo-2013 和 Metairie-2014 的百分比。莫昔克丁在较低浓度（<10 nM）下增加了附着细胞的两种抗性株的百分比，高于伊维菌素。PBMC 和 PMN 的附着并没有导致寄生虫在体外任何杀伤。这些数据支持了犬白细胞对犬恶丝虫 Mf 的药物刺激附着的生物学相关性，并表明这种现象与寄生虫的耐药状态有关。
