Macrocyclic lactone resistance in Dirofilaria immitis: risks for prevention of heartworm disease

SUMMARYPrevention of heartworm disease caused by Dirofilaria immitis in domestic dogs and cats relies on a single drug class, the macrocyclic lactones (MLs). Recently, it has been demonstrated that ML-resistant D. immitis are circulating in the Mississippi Delta region of the USA, but the prevalence and impact of these resistant parasites remains unknown. We review published studies that demonstrated resistance in D.immitis, along with our current understanding of its mechanisms. Efforts to develop in vitro tests for resistance have not yet yielded a suitable assay, so testing infected animals for microfilariae that persist in the face of ML treatment may be the best current option. Since the vast majority of D. immitis populations continue to be drug-sensitive, protected dogs are likely to be infected with only a few parasites and experience relatively mild disease. In cats, infection with small numbers of worms can cause severe disease and so the clinical consequences of drug resistance may be more severe. Since melarsomine dihydrochloride, the drug used to remove adult worms, is not an ML, the ML-resistance should have no impact on our ability to treat diseased animals. A large refugium of heartworms that are not exposed to drugs exists in unprotected dogs and in wild canids, which may limit the development and spread of resistance alleles.

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Using population genetics to examine relationships of Dirofilaria immitis based on both macrocyclic lactone-resistance status and geography

Veterinary Parasitology ◽

10.1016/j.vetpar.2020.109125 ◽

2020 ◽

Vol 283 ◽

pp. 109125 ◽

Cited By ~ 2

Author(s):

Julie Sanchez ◽

Guha Dharmarajan ◽

Melissa M. George ◽

Cassan Pulaski ◽

Adrian J. Wolstenholme ◽

...

Keyword(s):

Population Genetics ◽

Dirofilaria Immitis ◽

Macrocyclic Lactone ◽

Macrocyclic Lactone Resistance

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Macrocyclic lactone resistance in Dirofilaria immitis

Veterinary Parasitology ◽

10.1016/j.vetpar.2011.04.012 ◽

2011 ◽

Vol 181 (2-4) ◽

pp. 388-392 ◽

Cited By ~ 47

Author(s):

Catherine Bourguinat ◽

Kathy Keller ◽

Aron Bhan ◽

Andrew Peregrine ◽

Timothy Geary ◽

...

Keyword(s):

Dirofilaria Immitis ◽

Macrocyclic Lactone ◽

Macrocyclic Lactone Resistance

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Macrocyclic lactone resistance in Dirofilaria immitis by Bourguinat et al.

Veterinary Parasitology ◽

10.1016/j.vetpar.2011.06.008 ◽

2011 ◽

Vol 182 (2-4) ◽

pp. 380-381

Author(s):

Catherine Bourguinat ◽

Aron Bhan ◽

Andrew Peregrine ◽

Timothy Geary ◽

Roger Prichard

Keyword(s):

Dirofilaria Immitis ◽

Macrocyclic Lactone ◽

Macrocyclic Lactone Resistance

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Nematode ligand-gated chloride channels: an appraisal of their involvement in macrocyclic lactone resistance and prospects for developing molecular markers

Parasitology ◽

10.1017/s0031182007000042 ◽

2007 ◽

Vol 134 (8) ◽

pp. 1111-1121 ◽

Cited By ~ 51

Author(s):

S. McCAVERA ◽

T. K. WALSH ◽

A. J. WOLSTENHOLME

Keyword(s):

Haemonchus Contortus ◽

Chloride Channels ◽

Macrocyclic Lactone ◽

Parasitic Nematodes ◽

C Elegans ◽

Molecular Tests ◽

Cooperia Oncophora ◽

Macrocyclic Lactone Resistance ◽

High Level ◽

Laboratory Models

SUMMARYLigand-gated chloride channels, including the glutamate-(GluCl) and GABA-gated channels, are the targets of the macrocyclic lactone (ML) family of anthelmintics. Changes in the sequence and expression of these channels can cause resistance to the ML in laboratory models, such as Caenorhabditis elegans and Drosophila melanogaster. Mutations in multiple GluCl subunit genes are required for high-level ML resistance in C. elegans, and this can be influenced by additional mutations in gap junction and amphid genes. Parasitic nematodes have a different complement of channel subunit genes from C. elegans, but a few genes, including avr-14, are widely present. A polymorphism in an avr-14 orthologue, which makes the subunit less sensitive to ivermectin and glutamate, has been identified in Cooperia oncophora, and polymorphisms in several subunits have been reported from resistant isolates of Haemonchus contortus. This has led to suggestions that ML resistance may be polygenic. Possible reasons for this, and its consequences for the development of molecular tests for resistance, are explored.

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