Moxidectin‐resistant Haemonchus contortus in sheep in northern New South Wales

Love, S. C. J.; Neilson, F.J.A.; Biddle, A. J.; McKinnon, R

doi:10.1111/j.1751-0813.2003.tb11514.x

Cited by 53 publications

(25 citation statements)

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“…(ii) Wallangra (WAL): isolated from the New England region of Northern New South Wales in 2003; at the time of isolation from the field it was resistant to benzimidazoles, closantel, levamisole (LEV) and IVM (Love et al, 2003). The isolate has been further selected using moxidectin (Cydectin ® ) over at least five generations.…”

Section: Parasitesmentioning

confidence: 99%

Effects of third generation P-glycoprotein inhibitors on the sensitivity of drug-resistant and -susceptible isolates of Haemonchus contortus to anthelmintics in vitro

Raza

Kopp

Jabbar

et al. 2015

Veterinary Parasitology

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Section: Parasitesmentioning

confidence: 99%

Effects of third generation P-glycoprotein inhibitors on the sensitivity of drug-resistant and -susceptible isolates of Haemonchus contortus to anthelmintics in vitro

Raza

Kopp

Jabbar

et al. 2015

Veterinary Parasitology

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“…The wide use of anthelmintic combinations, often necessitated by the very high frequency of resistance to one or more available constituent actives when used alone, has revealed no issues of special concern with the routine use of such products. It was to be expected that some multiply-resistant nematode populations (e.g., Love et al, 2003;Wrigley et al, 2006;Sutherland et al, 2008;Baker et al, 2012) would ultimately be found in countries where combinations were used, given the long history of use of their components as single-constituent active anthelmintic products, generating high 'pre-existing' resistance (R)-allele frequencies in exposed parasite populations.…”

Section: Managing Existing Resistancementioning

confidence: 99%

“…For the purposes of this guideline, AR may be simply defined as a heritable change in susceptibility to an anthelmintic in a population of parasitic nematodes such that a dose which normally provides ≥95% clearance of adult worms provides ≤80% clearance. Anthelmintic resistance is arguably the greatest threat to the sustainable control of helminthoses in the short-to medium-term and the problem is compounded by the fact that many of these parasite populations are resistant to more than one class of anthelmintic (van Wyk et al, 1997;Love et al, 2003;Anziani et al, 2004;Wrigley et al, 2006;Sargison et al, 2007;Sutherland et al, 2008;Gasbarre et al, 2009a,b;Cezar et al, 2010;Baker et al, 2012;Molento et al, 2012;Reinemeyer, 2012). Despite the scarcity of well-structured surveys, it is generally accepted that the prevalence of AR is increasing globally in the ruminant livestock industries and in horses.…”

Section: Introductionmentioning

confidence: 99%

World Association for the Advancement of Veterinary Parasitology (W.A.A.V.P.) Guideline: Anthelmintic combination products targeting nematode infections of ruminants and horses

Geary

Hosking

Skuce

et al. 2012

Veterinary Parasitology

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a b s t r a c tIncreasing threats from anthelmintic resistant nematode populations warrant and motivate a reappraisal of chemotherapeutic strategies for nematode control in ruminant livestock and horses. The objective of this paper is to present a guideline for the evaluation of products containing two or more constituent anthelmintic actives in a single dosage form for the treatment of nematode infections in these animals. At present, regulatory policies on the approval of such products vary across jurisdictions, and this World Association for the Advancement of Veterinary Parasitology (W.A.A.V.P.) guideline should enable the harmonization of the requirements. This guideline makes clear recommendations on the minimal standards needed, but stresses that registration dossiers for combination anthelmintic products submitted for approval must conform to the standards and practices already established in existing guidelines for anthelmintics.

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“…Two isolates of H. contortus were used for the present study: the drug-susceptible Kirby isolate (Albers and Burgess, 1988) and the multi-drug-resistant Wallangra (WAL) isolate (Love et al, 2003). Infections were maintained in sheep at the CSIRO Agriculture FD McMaster laboratory, Armidale, New South Wales (NSW), and faecal samples were collected and transported to the CSIRO laboratories in Brisbane, QLD.…”

Section: Parasites and Chemicalsmentioning

confidence: 99%

Synergism between ivermectin and the tyrosine kinase/ P -glycoprotein inhibitor crizotinib against Haemonchus contortus larvae in vitro

Raza

Kopp

Kotze

2016

Veterinary Parasitology

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2 Graphical abstract3 Highlights:-we examined interaction of P-gp inhibitor crizotinib with ivermectin in Haemonchus contortus larvae in vitro -crizotinib increased the toxicity of ivermectin towards a resistant isolate in migration assays -less synergism observed in larval development assays -assay differences suggest life-stage specific patterns of ivermectin / P-gp interaction.-study highlights potential of P-gp inhibitors to reverse ivermectin resistance AbstractAnthelmintic resistance is a major problem in parasitic nematodes of livestock worldwide. One means to counter resistance is to use synergists that specifically inhibit resistance mechanisms in order to restore the toxicity, and hence preserve the usefulness, of currently available anthelmintics. P-glycoproteins (P-gps) eliminate a wide variety of structurally unrelated xenobiotics from cells, and have been implicated in anthelmintic resistance. Crizotinib is a tyrosine kinase inhibitor under development as a cancer therapeutic.The compound also inhibits P-gps, and has been shown to reverse multidrug resistance in cancer cells. We were therefore interested in determining if the compound was able to increase the sensitivity of Haemonchus contortus larvae to ivermectin, as measured by in vitro larval development and migration assays with a drug-resistant and a -susceptible isolate. In migration assays, co-administration of crizotinib increased the toxicity of ivermectin to resistant larvae (up to 5.7-fold decrease in ivermectin IC50), and rendered the resistant larvae equally or more sensitive to ivermectin than the susceptible isolate. On the other hand, co-administration of crizotinib had no effect on ivermectin sensitivity in the 4 susceptible isolate. In development assays, significant increases in the sensitivity of both the resistant (up to 1.9-fold) and susceptible (up to 1.6-fold) larvae to ivermectin were observed , although the magnitude of the observed synergism was less than seen in migration assays, and the resistant larvae retained significant levels of ivermectin resistance. By highlighting the ability of the P-gp inhibitor crizotinib to increase the sensitivity of H. contortus larvae to ivermectin, this study provides further evidence that P-gp inhibitors are potential tools for modulating the efficacy of anthelmintics. In addition, the differences in the outcomes of the two assays, with 'resistance-breaking' effects being much more marked in migration assays, suggest that some life-stage-specific aspects may exist in the interaction of ivermectin with Pgps in the two worm isolates.

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Moxidectin‐resistant Haemonchus contortus in sheep in northern New South Wales

Cited by 53 publications

References 4 publications

Effects of third generation P-glycoprotein inhibitors on the sensitivity of drug-resistant and -susceptible isolates of Haemonchus contortus to anthelmintics in vitro

Effects of third generation P-glycoprotein inhibitors on the sensitivity of drug-resistant and -susceptible isolates of Haemonchus contortus to anthelmintics in vitro

World Association for the Advancement of Veterinary Parasitology (W.A.A.V.P.) Guideline: Anthelmintic combination products targeting nematode infections of ruminants and horses

Synergism between ivermectin and the tyrosine kinase/ P -glycoprotein inhibitor crizotinib against Haemonchus contortus larvae in vitro

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