Exploration of the sensitivity to macrocyclic lactones in the canine heartworm (Dirofilaria immitis) in Australia using phenotypic and genotypic approaches

Power, Rosemonde Isabella; Šlapeta, Jan

doi:10.1016/j.ijpddr.2022.11.003

Cited by 5 publications

(4 citation statements)

References 38 publications

(102 reference statements)

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“…Analysis of allele frequency in our studied populations showed that these variants are present at a moderate frequency in the USA but are largely absent or are fixed variants unlikely to be associated with resistance from Italy and Australian samples (Fig. 2e; bottom panel), consistent with previous studies (Curry et al, 2022b;Power and Šlapeta, 2022). The relevance of these predictive variants outside of the USA is unknown and requires further validation with phenotypically defined non-USA isolates.…”

Section: Chromosomal Context Of Genetic Markers Associated With Iverm...supporting

confidence: 84%

“…(i) twelve pooled microfilaria samples from Queensland (QLD), Australia. These Australian blood samples (32 to 38,250 microfilaria.ml -1 ) and their DNA were included in a previous study of ML resistance in Australia (Power and Šlapeta, 2022). Extracted DNA from filtered microfilariae of D. immitis from 2019 (HW3/19, HW4/19) and 2020 (HW5/20 to HW9/20, HW12/20 to HW16/20) were sent to Novogene (HK) Co., Ltd for indexing, library .…”

Section: Additional Unpublished Datasetsmentioning

confidence: 99%

“…Subsequently, this initial set of genetic variants was re-assessed and reduced to 10-and two-SNP panels, validated using clinical samples, that were proposed to discriminate between susceptible and ML-resistant parasites (Ballesteros et al, 2018). This small panel of SNPs has been examined in European and Australian samples; however, additional support for these markers was not provided due to the lack of phenotypicallydefined resistant isolates (Curry et al, 2022b;Power and Šlapeta, 2022). One caveat to the genome-to-SNPs approach was that the initial analyses were performed on a fragmented genome assembly and without a firm understanding of the genetic diversity within and between isolates, which can lead to both biological and technical biases that can confound association studies for genetic traits such as drug resistance .…”

Section: Introductionmentioning

confidence: 99%

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Genome structure and population genomics of the canine heartwormDirofilaria immitis

Gandasegui

Power

Curry

et al. 2023

Preprint

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The heartworm, Dirofilaria immitis, is a filarial parasitic nematode responsible for significant morbidity and mortality in wild and domesticated canids. Resistance to macrocyclic lactone drug prevention represents a significant threat to parasite control and has prompted investigations to understand the genetic determinants of resistance. This study aimed to improve the genomic resources of D. immitis to enable a more precise understanding of how genetic variation is distributed within and between parasite populations worldwide, which will inform the likelihood and rate by which parasites, and in turn, resistant alleles, might spread. We have guided the scaffolding of a recently published genome assembly for D. immitis (ICBAS_JMDir_1.0) using the chromosomal-scale reference genomes of Brugia malayi and Onchocerca volvulus, resulting in an 89.5 Mb assembly composed of four autosomal- and one X-linked chromosomal-scale scaffolds representing 99.7% of the genome. Publicly available and new whole-genome sequencing data from 32 D. immitis samples from Australia, Italy and the USA were assessed using principal component analysis, nucleotide diversity (Pi) and absolute genetic divergence (Dxy) to characterise the global genetic structure and measure within- and between population diversity. These population genetic analyses revealed broad-scale genetic structure among globally diverse samples and differences in genetic diversity between populations; however, fine-scale subpopulation analysis was limited and biased by differences between sample types. Finally, we mapped SNPs previously associated with macrocyclic lactone resistance in the new genome assembly, revealing physical linkage of high-priority variants on chromosome 3, and determined their frequency in the studied populations. This new chromosomal assembly for D. immitis now allows for a more precise investigation of selection on genome-wide genetic variation and will enhance our understanding of parasite transmission and the spread of genetic variants responsible for resistance to treatment.

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Section: Chromosomal Context Of Genetic Markers Associated With Iverm...supporting

confidence: 84%

Section: Additional Unpublished Datasetsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Genome structure and population genomics of the canine heartwormDirofilaria immitis

Gandasegui

Power

Curry

et al. 2023

Preprint

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“…Suspected cases have been investigated, but results have so far not confirmed resistance to MLs in Europe ( 67 , 68 ). Although also suspected in Australia, genotypic assays have not yet unequivocally demonstrated the presence of ML-resistant D. immitis ( 6 , 69 ).…”

Section: Efficacy Of Macrocyclic Lactones In View Of Resistant ...mentioning

confidence: 99%

A review of moxidectin vs. other macrocyclic lactones for prevention of heartworm disease in dogs with an appraisal of two commercial formulations

Mwacalimba,

Sheehy,

Adolph

et al. 2024

Front. Vet. Sci.

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Macrocyclic lactones (MLs) are the only drug class currently licensed for heartworm disease prophylaxis. Macrocyclic lactones kill third- and fourth-stage larvae of Dirofilaria immitis, thus preventing the development of adult worms in dogs, which are responsible for heartworm disease, a potentially life-threatening condition. Despite considerable overlap in terms of endectocide spectrum, several important differences distinguish moxidectin from other MLs. Moxidectin has beneficial pharmacokinetic characteristics, such as a longer half-life and greater tissue distribution compared to ivermectin. Additionally, moxidectin has a greater margin of safety compared to ivermectin in dogs with ABCB1 (previously MDR1) gene-defect, which is commonly recognized in collies and other breeds. Multiple laboratory studies have shown that moxidectin is more effective than other commonly used heartworm preventives against resistant strains of D. immitis. This improved efficacy benefits individual dogs and helps reduce the risk of spreading resistant strains within the community. Despite the presence of proven resistant strains in the United States, non-compliance with preventive measures remains a major factor contributing to the diagnosis of heartworm disease in dogs. In retrospective analyses, the oral moxidectin combination product Simparica Trio® (sarolaner, moxidectin, and pyrantel) was associated with increased compliance, resulting in more time of protection compared to dogs receiving flea/tick and heartworm preventive products separately. Compliance with the extended-release moxidectin injectables ProHeart® 6 and ProHeart® 12 was higher than with monthly heartworm preventives, as they provide 6 months or a full year of protection with one single injection, respectively, and revenues remain in the veterinary clinics as injectable moxidectin cannot be sourced through online retailers.

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Whole genome amplification and sequencing of individual Dirofilaria immitis microfilariae

Power,

Doyle,

Šlapeta

2024

Experimental Parasitology

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Exploration of the sensitivity to macrocyclic lactones in the canine heartworm (Dirofilaria immitis) in Australia using phenotypic and genotypic approaches

Cited by 5 publications

References 38 publications

Genome structure and population genomics of the canine heartwormDirofilaria immitis

Genome structure and population genomics of the canine heartwormDirofilaria immitis

A review of moxidectin vs. other macrocyclic lactones for prevention of heartworm disease in dogs with an appraisal of two commercial formulations

Whole genome amplification and sequencing of individual Dirofilaria immitis microfilariae

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