Macrocyclic lactone anthelmintic-induced leukocyte binding to Dirofilaria immitis microfilariae: Influence of the drug resistance status of the parasite

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...

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Bibliographic Details
Published in:International journal for parasitology -- drugs and drug resistance 2019-08, Vol.10, p.45-50
Main Authors: Berrafato, Tessa, Coates, Ruby, Reaves, Barbara J., Kulke, Daniel, Wolstenholme, Adrian J.
Format: Article
Language:English
Subjects:
Animals
Anthelmintics - administration & dosage
Anthelmintics - chemistry
Cell Adhesion - drug effects
Dirofilaria immitis
Dirofilaria immitis - drug effects
Dirofilaria immitis - physiology
Dirofilariasis - parasitology
Dog Diseases - drug therapy
Dog Diseases - parasitology
Dog Diseases - physiopathology
Dogs
Drug Resistance
Female
Ivermectin
Lactones - administration & dosage
Lactones - chemistry
Leukocytes, Mononuclear - cytology
Leukocytes, Mononuclear - drug effects
Male
Microfilariae - drug effects
Microfilariae - physiology
Moxidectin
Peripheral blood mononuclear cells
Polymorphonuclear leukocytes
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Summary: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 (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 (
ISSN:2211-3207
2211-3207
DOI:10.1016/j.ijpddr.2019.04.004